59 results on '"Diane L. Carlson"'
Search Results
2. Figure S2 from Genomic Alterations in Fatal Forms of Non-Anaplastic Thyroid Cancer: Identification of MED12 and RBM10 as Novel Thyroid Cancer Genes Associated with Tumor Virulence
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Ian Ganly, Ronald Ghossein, James A. Fagin, Timothy Chan, R. Michael Tuttle, Luc Morris, Michael F. Berger, Brian Untch, Jeffrey A. Knauf, Jocelyn Migliacci, Diane L. Carlson, Shyam Deraje, Venkatraman Seshan, Sumit Middha, Snjezana Dogan, Iñigo Landa, Bin Xu, and Tihana Ibrahimpasic
- Abstract
Mutations in DNA damage control (A), RAS/PI3K/AkT/MTOR pathways (B), chromatin modifying genes (C) and receptor tyrosine kinase genes (RTKs) (D) in fatal non-anaplastic thyroid cancer.
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- 2023
3. Table S1 from Genomic Alterations in Fatal Forms of Non-Anaplastic Thyroid Cancer: Identification of MED12 and RBM10 as Novel Thyroid Cancer Genes Associated with Tumor Virulence
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Ian Ganly, Ronald Ghossein, James A. Fagin, Timothy Chan, R. Michael Tuttle, Luc Morris, Michael F. Berger, Brian Untch, Jeffrey A. Knauf, Jocelyn Migliacci, Diane L. Carlson, Shyam Deraje, Venkatraman Seshan, Sumit Middha, Snjezana Dogan, Iñigo Landa, Bin Xu, and Tihana Ibrahimpasic
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List of 410 genes in IMPACT sequencing platform
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- 2023
4. Supplementary legend from Genomic Alterations in Fatal Forms of Non-Anaplastic Thyroid Cancer: Identification of MED12 and RBM10 as Novel Thyroid Cancer Genes Associated with Tumor Virulence
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Ian Ganly, Ronald Ghossein, James A. Fagin, Timothy Chan, R. Michael Tuttle, Luc Morris, Michael F. Berger, Brian Untch, Jeffrey A. Knauf, Jocelyn Migliacci, Diane L. Carlson, Shyam Deraje, Venkatraman Seshan, Sumit Middha, Snjezana Dogan, Iñigo Landa, Bin Xu, and Tihana Ibrahimpasic
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Supplementary legend
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- 2023
5. Figure S3 from Genomic Alterations in Fatal Forms of Non-Anaplastic Thyroid Cancer: Identification of MED12 and RBM10 as Novel Thyroid Cancer Genes Associated with Tumor Virulence
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Ian Ganly, Ronald Ghossein, James A. Fagin, Timothy Chan, R. Michael Tuttle, Luc Morris, Michael F. Berger, Brian Untch, Jeffrey A. Knauf, Jocelyn Migliacci, Diane L. Carlson, Shyam Deraje, Venkatraman Seshan, Sumit Middha, Snjezana Dogan, Iñigo Landa, Bin Xu, and Tihana Ibrahimpasic
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Comparison of the most commonly mutated genes in fatal WDTC compared to nonfatal WDTC (TCGA)is shown in (A). Comparison of the most commonly mutated genes in fatal PDTC compared to nonfatal PDTC is shown in (B).
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- 2023
6. Supplementary Table 2. from Genomic Alterations in Fatal Forms of Non-Anaplastic Thyroid Cancer: Identification of MED12 and RBM10 as Novel Thyroid Cancer Genes Associated with Tumor Virulence
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Ian Ganly, Ronald Ghossein, James A. Fagin, Timothy Chan, R. Michael Tuttle, Luc Morris, Michael F. Berger, Brian Untch, Jeffrey A. Knauf, Jocelyn Migliacci, Diane L. Carlson, Shyam Deraje, Venkatraman Seshan, Sumit Middha, Snjezana Dogan, Iñigo Landa, Bin Xu, and Tihana Ibrahimpasic
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All IMPACT mutation calls. Tumors previously published by Landa et al (1) are highlighted in blue.
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- 2023
7. Data from Genomic Alterations in Fatal Forms of Non-Anaplastic Thyroid Cancer: Identification of MED12 and RBM10 as Novel Thyroid Cancer Genes Associated with Tumor Virulence
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Ian Ganly, Ronald Ghossein, James A. Fagin, Timothy Chan, R. Michael Tuttle, Luc Morris, Michael F. Berger, Brian Untch, Jeffrey A. Knauf, Jocelyn Migliacci, Diane L. Carlson, Shyam Deraje, Venkatraman Seshan, Sumit Middha, Snjezana Dogan, Iñigo Landa, Bin Xu, and Tihana Ibrahimpasic
- Abstract
Purpose: Patients with anaplastic thyroid cancer (ATC) have a very high death rate. In contrast, deaths from non-anaplastic thyroid (NAT) cancer are much less common. The genetic alterations in fatal NAT cancers have not been reported.Experimental Design: We performed next-generation sequencing of 410 cancer genes from 57 fatal NAT primary cancers. Results were compared with The Cancer Genome Atlas study (TCGA study) of papillary thyroid cancers (PTCs) and to the genomic changes reported in ATC.Results: There was a very high prevalence of TERT promoter mutations, comparable with that of ATC, and these co-occurred with BRAF and RAS mutations. A high incidence of chromosome 1q gain was seen highlighting its importance in tumor aggressiveness. Two novel fusion genes DLG5–RET and OSBPL1A–BRAF were identified. There was a high frequency of mutations in MED12 and these were mutually exclusive to TERT promoter mutations and also to BRAF and RAS mutations. In addition, a high frequency of mutations in RBM10 was identified and these co-occurred with RAS mutations and PIK3CA mutations. Compared with the PTCs in TCGA, there were higher frequencies of mutations in TP53, POLE, PI3K/AKT/mTOR pathway effectors, SWI/SNF subunits, and histone methyltransferases.Conclusions: These data support a model, whereby fatal NAT cancers arise from well-differentiated tumors through the accumulation of key additional genetic abnormalities. The high rate of TERT promoter mutations, MED12 mutations, RBM10 mutations, and chromosome 1q gain highlight their likely association with tumor virulence. Clin Cancer Res; 23(19); 5970–80. ©2017 AACR.
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- 2023
8. Clinical and Pathologic Features Associated With Invasive Breast Carcinoma With 2018 American Society of Clinical Oncology/College of American Pathologists In Situ Hybridization Group 2 Results (Human Epidermal Growth Factor Receptor 2 [HER2]/Chromosome 17 Centromere [CEP17] Ratio ≥2.0 and Average HER2 Copy Number <4.0)
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Cathy Sprague, Yasmin Mekhail, Raza S Hoda, Erinn Downs-Kelly, Diane L. Carlson, Patrick J McIntire, Miglena K. Komforti, and Shabnam Zarei
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Oncology ,medicine.medical_specialty ,DNA Copy Number Variations ,Receptor, ErbB-2 ,Centromere ,Breast Neoplasms ,In situ hybridization ,Medical Oncology ,Chromosome 17 Centromere ,Pathology and Forensic Medicine ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,Prospective Studies ,neoplasms ,In Situ Hybridization, Fluorescence ,Retrospective Studies ,Clinical Oncology ,medicine.diagnostic_test ,business.industry ,Retrospective cohort study ,General Medicine ,Guideline ,Pathologists ,Medical Laboratory Technology ,Immunohistochemistry ,Female ,Breast carcinoma ,business ,Chromosomes, Human, Pair 17 ,Fluorescence in situ hybridization - Abstract
Context.— The American Society of Clinical Oncology/College of American Pathologists updated the human epidermal growth factor receptor 2 (HER2) breast carcinoma testing guideline in 2018 to address issues from uncommon HER2 fluorescence in situ hybridization (FISH) results. Based on the 2013 American Society of Clinical Oncology/College of American Pathologists guideline, cases wherein the HER2/chromosome 17 centromere (CEP17) ratio of 2.0 or more with an average HER2 copy number of less than 4.0 were considered in situ hybridization (ISH) positive. Under the 2018 guideline, such cases are classified as ISH Group 2 and are no longer considered eligible for anti-HER2 therapy when the corresponding HER2 immunohistochemistry result is 0, 1+, or 2+. Objective.— To assess the clinical, pathologic, and treatment aspects of patients with ISH Group 2 results. Design.— We retrospectively reviewed HER2 FISH results at our center between January 2012 and December 2014 and identified and characterized cases with ISH Group 2 results. Results.— Thirty-nine cases with ISH Group 2 results from 39 patients were reviewed. Twenty of 39 (51%) patients received anti-HER2 therapy. Patients treated with HER2-targeted therapy were less likely to have hormone receptor–positive tumors, compared with patients without anti-HER2 treatment, though not significantly (P = .30). The only significant difference between the 2 patient groups was receipt of cytotoxic chemotherapy treatment (P < .001). Overall, clinical outcome was similar between the 2 groups (P > .99). Conclusions.— This retrospective study with median follow-up of at least 6 years shows patients with ISH Group 2 tumors had similar clinical outcomes, irrespective of HER2-targeted therapy. Further analysis in the prospective setting would provide valuable data that would potentially inform clinical decision making.
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- 2021
9. Data Set for the Reporting of Carcinomas of the Nasopharynx and Oropharynx: Explanations and Recommendations of the Guidelines From the International Collaboration on Cancer Reporting
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Timothy R. Helliwell, John M. Nicholls, Abbas Agaimy, Diane L. Carlson, James S. Lewis, William C. Faquin, Brian O'Sullivan, Tony Ng, Lester D.R. Thompson, Jos Hille, and David J. Adelstein
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0301 basic medicine ,medicine.medical_specialty ,MEDLINE ,Datasets as Topic ,Article ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,Cancer control ,Humans ,Medicine ,Human papillomavirus ,Minimum Data Set ,Pathology, Clinical ,business.industry ,Carcinoma ,Cancer ,Nasopharyngeal Neoplasms ,General Medicine ,medicine.disease ,Oropharyngeal Neoplasms ,Medical Laboratory Technology ,030104 developmental biology ,Depth of invasion ,030220 oncology & carcinogenesis ,Family medicine ,Practice Guidelines as Topic ,business ,Oncovirus - Abstract
The International Collaboration on Cancer Reporting was established to internationally unify and standardize the pathologic reporting of cancers based on collected evidence, as well as to allow systematic data collection across institutions and countries to guide cancer care in the future. An expert panel was convened to identify the minimum data set of elements that should be included in cancer reporting from tumors of the nasopharynx and oropharynx. Specifically, there has been a significant change in practice as a result of identifying oncogenic viruses, including human papillomavirus and Epstein-Barr virus, because they preferentially affect the oropharynx and nasopharynx, respectively. For these anatomic sites, when viral association is taken into account, usually reported elements of in situ versus invasive tumor, depth of invasion, and degree of differentiation are no longer applicable. Thus, guidance about human papillomavirus testing in oropharyngeal carcinomas and Epstein-Barr virus testing in nasopharyngeal carcinomas is highlighted. Further, the clinical and the pathologic differences in staging as proposed by the 8th edition of the Union for International Cancer Control are incorporated into the discussion, pointing out several areas of continued study and further elaboration. A summary of the International Collaboration on Cancer Reporting guidelines for oropharyngeal and nasopharyngeal carcinomas is presented, along with discussion of the salient evidence and practical issues.
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- 2018
10. Data Set for the Reporting of Nodal Excisions and Neck Dissection Specimens for Head and Neck Tumors: Explanations and Recommendations of the Guidelines From the International Collaboration on Cancer Reporting
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Jonathan J. Beitler, Jennifer L. Hunt, Isabel Fonseca, Michelle D. Williams, Diane L. Carlson, Nora Katabi, Martin Bullock, Philip Sloan, Lester D.R. Thompson, and S. Mark Taylor
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0301 basic medicine ,medicine.medical_specialty ,medicine.medical_treatment ,Datasets as Topic ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,Text mining ,medicine ,Humans ,Pathology, Clinical ,business.industry ,Head and neck tumors ,Cancer ,Neck dissection ,General Medicine ,medicine.disease ,Data set ,Medical Laboratory Technology ,030104 developmental biology ,Head and Neck Neoplasms ,030220 oncology & carcinogenesis ,Practice Guidelines as Topic ,Lymph Node Excision ,Neck Dissection ,Radiology ,business - Abstract
Standardized, synoptic pathologic reporting for tumors greatly improves communication among clinicians, patients, and researchers, supporting prognostication and comparison about patient outcomes across institutions and countries. The International Collaboration on Cancer Reporting is a nonprofit organization whose mission is to develop evidence-based, universally available surgical pathology reporting data sets. Within the head and neck region, lymph node excisions and neck dissections are frequently performed as part of the management of head and neck cancers arising from the mucosal sites (sinonasal tract, nasopharynx, oropharynx, hypopharynx, oral cavity, and larynx) along with bone tumors, skin cancers, melanomas, and other tumor categories. The type of specimen, exact location (lymph node level), laterality, and orientation (by suture or diagram) are essential to accurate classification. There are significant staging differences for each anatomic site within the head and neck when lymph node sampling is considered, most importantly related to human papillomavirus–associated oropharyngeal carcinomas and mucosal melanomas. Number, size, and site of affected lymph nodes, including guidelines on determining the size of tumor deposits and the presence of extranodal extension and soft tissue metastasis, are presented in the context of prognostication. This review elaborates on each of the elements included in the data set for Nodal Excisions and Neck Dissection Specimens for Head & Neck Tumours.
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- 2018
11. Oncolytic Herpes Simplex Virus Prevents Premalignant Lesions from Progressing to Cancer
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Yanghee Woo, Yuman Fong, Zhenkun Yu, Vincent Reid, Kaitlyn J. Kelly, and Diane L. Carlson
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0301 basic medicine ,Cancer Research ,medicine.disease_cause ,lcsh:RC254-282 ,Virus ,Article ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Carcinoma ,Pharmacology (medical) ,viral tropism ,oncolytic virotherapy ,early cancer diagnosis ,Cancer prevention ,oral squamous carcinoma ,cancer prevention ,business.industry ,Cancer ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,herpes simplex virus ,3. Good health ,Oncolytic virus ,030104 developmental biology ,Herpes simplex virus ,Oncology ,030220 oncology & carcinogenesis ,Tissue tropism ,Cancer research ,Molecular Medicine ,Carcinogenesis ,business ,carcinogenesis - Abstract
Early detection and timely treatment of precancerous lesions are hallmarks of successful strategies to prevent deaths due to cancer. Oncolytic viruses are a group of promising anti-cancer agents with wide-ranging experimental and clinical efficacy against solid tumors. Previously, we have shown that NV1066, an oncolytic herpes simplex-1 virus encoding enhanced green fluorescent protein, selectively infects, replicates in, and kills various cancer types. In this study, we sought to determine whether this oncolytic agent can treat precancerous lesions to prevent cancer formation. Using an oral chemical carcinogenesis model in hamsters, we assessed the ability of NV1066 to infect precancerous and cancerous lesions. NV1066 consistently infected dysplastic cells, carcinoma in situ, and squamous cell carcinoma. Animals receiving an intramucosal injection of NV1066 for 7 weeks showed significantly fewer (3-fold) and smaller (4-fold) lesions compared to animals that did not receive viral treatment. Results indicate that infectivity might be dependent on the herpes simplex virus 1 receptor, nectin-1. This study demonstrates that not only can NV1066 treat oral squamous cell carcinoma, but it can also infect and treat premalignant lesions, thus delaying cancer progression. Overall, our study shows the potential of the oncolytic virus NV1066 as a cancer prevention tool. Keywords: cancer prevention, carcinogenesis, early cancer diagnosis, oncolytic virotherapy, oral squamous carcinoma, herpes simplex virus, viral tropism
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- 2018
12. Influence of extracapsular nodal spread extent on prognosis of oral squamous cell carcinoma
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Jocelyn C. Migliacci, Frank L. Palmer, Ian Ganly, Jatin P. Shah, Snehal G. Patel, Mithat Gonen, Pablo H. Montero, Nora Katabi, Diane L. Carlson, Ronald Ghossein, and Volkert B. Wreesmann
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Pathology ,medicine.medical_specialty ,genetic structures ,business.industry ,Extranodal Extension ,medicine.medical_treatment ,Neck dissection ,medicine.disease ,Head and neck squamous-cell carcinoma ,stomatognathic diseases ,03 medical and health sciences ,0302 clinical medicine ,Otorhinolaryngology ,Neoplasm Invasiveness ,030220 oncology & carcinogenesis ,Medicine ,Basal cell ,030223 otorhinolaryngology ,business ,NODAL - Abstract
Background An objective definition of clinically relevant extracapsular nodal spread (ECS) in head and neck squamous cell carcinoma (SCC) is unavailable.
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- 2015
13. Outcomes in Patients With Poorly Differentiated Thyroid Carcinoma
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Diane L. Carlson, Jatin P. Shah, R. M. Tuttle, Ashok R. Shaha, Snehal G. Patel, Ronald Ghossein, Tihana Ibrahimpasic, Iain J. Nixon, Ian Ganly, and Frank L. Palmer
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Biochemistry ,Iodine Radioisotopes ,Young Adult ,Endocrinology ,Poorly Differentiated Thyroid Carcinoma ,Recurrence ,Internal medicine ,medicine ,Adjuvant therapy ,Humans ,Thyroid Neoplasms ,Young adult ,Thyroid cancer ,Aged ,Aged, 80 and over ,Proportional hazards model ,business.industry ,Carcinoma ,Biochemistry (medical) ,Thyroid ,Cancer ,Middle Aged ,Prognosis ,medicine.disease ,Combined Modality Therapy ,Log-rank test ,Treatment Outcome ,medicine.anatomical_structure ,Thyroidectomy ,Female ,business ,Follow-Up Studies - Abstract
Poorly differentiated thyroid cancer (PDTC) accounts for only 1-15% of all thyroid cancers. Our objective is to report outcomes in a large series of patients with PDTC treated at a single tertiary care cancer center.A total of 91 patients with primary PDTC were treated by initial surgery with or without adjuvant therapy at Memorial Sloan-Kettering Cancer Center from 1986 to 2009. Outcomes were calculated by the Kaplan-Meier method. Clinicopathological characteristics were compared for PDTC patients who died of disease to those who did not by the χ(2) test. Factors predictive of disease-specific survival (DSS) were calculated by univariate and multivariate analysis using the log rank and Cox proportional hazards method, respectively.With a median follow-up of 50 months, the 5-year overall survival and DSS were 62 and 66%, respectively. The 5-year locoregional and distant control were 81 and 59%, respectively. Of 27 disease-specific deaths, 23 (85%) were due to distant disease. Age ≥ 45 years, pathological tumor size4 cm, extrathyroidal extension, higher pathological T stage, positive margins, and distant metastases (M1) were predictive of worse DSS on univariate analysis. Multivariate analysis showed that only pT4a stage and M1 were independent predictors of worse DSS.With appropriate surgery and adjuvant therapy, excellent locoregional control can be achieved in PDTC. Disease-specific deaths occurred due to distant metastases and rarely due to uncontrolled locoregional recurrence in this series.
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- 2014
14. A phase 2 study of bevacizumab with cisplatin plus intensity-modulated radiation therapy for stage III/IVB head and neck squamous cell cancer
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Jatin P. Shah, Dennis H. Kraus, Matthew G. Fury, Katherine W. Kelly, David G. Pfister, Ronglai Shen, Sofia Haque, Nancy Y. Lee, Donna Lisa, Hilda E. Stambuk, Brynna Lipson, Diane L. Carlson, and Eric J. Sherman
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Oncology ,Cancer Research ,medicine.medical_specialty ,Bevacizumab ,Performance status ,business.industry ,medicine.medical_treatment ,Cancer ,Common Terminology Criteria for Adverse Events ,medicine.disease ,Head and neck squamous-cell carcinoma ,Sudden death ,Radiation therapy ,Internal medicine ,medicine ,Carcinoma ,business ,medicine.drug - Abstract
BACKGROUND: For patients with stage III through IVB head and neck squamous cell carcinoma (HNSCC), concurrent high-dose cisplatin plus radiation therapy is a widely accepted standard of care. HNSCC tumors that express high levels of vascular endothelial growth factor have been associated with a worse prognosis, and bevacizumab may sensitize tumors to cisplatin and radiation. METHODS: Planned treatment consisted of definitive intensity-modulated radiation therapy (IMRT) (total, 70 grays) with concurrent cisplatin (50 mg/m2 on days 1, 2, 22, 23, 43, and 44) and bevacizumab (15 mg/kg on days 1, 22, and 43). The primary endpoint was 2-year progression-free survival (PFS), and overall survival (OS) was a secondary endpoint. RESULTS: Forty-two previously untreated patients (34 men and 8 women; median age, 55 years; range, 27-75 years) with stage III through IV HNSCC without distant metastasis (oropharyngeal carcinoma, 39 patients; laryngeal carcinoma, 3 patients) were treated. Human papillomavirus (HPV) status by was determined by in situ hybridization (HPV positive, 16 patients; HPV negative, 14 patients, unknown HPV status, 12 patients). The toxicities (determined according to version 3.0 of Common Terminology Criteria for Adverse Events Common) that were experienced by all patients (any grade) were mucositis, lymphopenia, leukopenia, throat pain, fatigue, and anemia. There were 2 treatment-related deaths, including 1 sudden death and 1 death from aspiration pneumonia. The median follow-up was approximately 31.8 months (range
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- 2012
15. Association between Hyperprolactinemia and Granulomatous Mastitis
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Diane L. Carlson, Anatoly Nikolaev, and Cassann N. Blake
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Adenoma ,Adult ,Pathology ,medicine.medical_specialty ,Granulomatous mastitis ,Prolactin cell ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Pituitary adenoma ,Internal Medicine ,medicine ,Humans ,Pituitary Neoplasms ,030212 general & internal medicine ,Granulomatous Mastitis ,Prolactinoma ,Bromocriptine ,business.industry ,Pituitary tumors ,medicine.disease ,Craniopharyngioma ,Prolactin ,Hyperprolactinemia ,Oncology ,030220 oncology & carcinogenesis ,Dopamine Antagonists ,Surgery ,Female ,Ultrasonography, Mammary ,business - Abstract
Granulomatous mastitis (GM) is a relatively uncommon inflammatory breast lesion with multiple suggested etiologies. Although most GM cases show association with lactation and pregnancy, a minority of cases have been linked to hyperprolactinemia caused by either dopamine antagonist medications or with intracranial lesions, such as pituitary adenoma. The goal of this study is to review the GM cases reported in the literature with a specific emphasis on those cases associated with hyperprolactinemia and prolactinomas and to identify cases of GM seen at the Cleveland Clinic Florida which demonstrate co-occurrences of GM and intracranial lesions. CoPath and Epic data bases at Cleveland Clinic Florida were searched for cases describing inflammatory breast lesions in patients with pituitary pathology. Chart reviews were conducted and pertinent medical history was extracted for case reports. H&E-stained paraffin-embedded sections retrieved from Cleveland Clinic Florida pathology storage were evaluated by light microscopy. Four cases showing a co-occurrence of GM and hyperprolactinemia were consequently identified. A prolactin-secreting pituitary adenoma was present in two of the three GM cases. The third case demonstrated a concomitant craniopharyngioma, which was also associated with a rise in serum prolactin. This phenomenon was presumably attributable to compression, resulting in compromised transport of dopamine to the adenohypophysis and subsequent disinhibition of prolactin secretion by lactotrophs. The fourth patient with GM had a similar history of elevated prolactin. Classical histopathological features of GM were found in all four cases, including noncaseating granulomas, multinucleated giant cells, epithelioid histiocytes, and chronic inflammation. Intriguingly, complete resolution of inflammatory breast lesions along with normalization of prolactin levels occurred following the surgical excision of the craniopharyngioma, suggesting that intracranial lesion-induced hyperprolactinemia might be directly causal in GM. Therefore, the authors would suggest screening for pituitary tumors and evaluate prolactin levels in the workup of GM patients without a recent history of lactation and pregnancy and no other identified etiology.
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- 2015
16. A Histologic and Immunohistochemical Study Describing the Diversity of Tumors Classified as Sinonasal High-grade Nonintestinal Adenocarcinomas
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Vicky Y. Jo, Stacey E. Mills, Diane L. Carlson, and Edward B. Stelow
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Adult ,Male ,Nasal cavity ,medicine.medical_specialty ,Pathology ,Maxillary Sinus Neoplasms ,Mitosis ,Adenocarcinoma ,Pathology and Forensic Medicine ,Necrosis ,Young Adult ,Sinonasal undifferentiated carcinoma ,Mucoepidermoid carcinoma ,Intestinal Neoplasms ,Paranasal Sinuses ,Biomarkers, Tumor ,medicine ,Humans ,Nose ,Aged ,Aged, 80 and over ,Cell Nucleus ,business.industry ,Carcinoma ,Apocrine ,Anatomical pathology ,Histology ,Middle Aged ,medicine.disease ,Immunohistochemistry ,medicine.anatomical_structure ,Female ,Surgery ,Nasal Cavity ,Anatomy ,business - Abstract
Nonintestinal sinonasal adenocarcinomas (SNACs) are somewhat poorly characterized and high-grade nonintestinal SNACs have been only rarely reported. Here, we review our experience with these tumors. Twenty-seven cases of high-grade nonintestinal SNACs were identified from 22 men and 5 women. Ages ranged from 22 to 83 years (mean±1 standard deviation=54.7±18.6 y; median=60 y). Thirteen cases involved the nasal cavity and sinuses, 10 involved the nasal cavity only, and 4 involved sinuses only. Most cases had marked cytologic and nuclear pleomorphism, abundant mitotic activity, and necrosis; however, these features were not uniform. Although histologically heterogeneous, recurrent growth patterns were seen that resembled other neoplasms of the area. Tumors lacked CDX2 and CK20 immunoreactivity (aside from rare CK20 immunoreactive cells). High-grade nonintestinal SNACs are more common in men and, although they occur over a wide age range, they are much more common in older individuals. Histologically, they show a great deal of heterogeneity.
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- 2011
17. Tissue microarray evidence of association between p16 and phosphorylated eIF4E in tonsillar squamous cell carcinoma
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Camelia S. Sima, David G. Pfister, Marija Drobnjak, Marina Asher, Nancy Y. Lee, Jatin P. Shah, H. Guido Wendel, Matthew G. Fury, and Diane L. Carlson
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Adult ,Cyclin-Dependent Kinase Inhibitor p21 ,Male ,Tonsillar Neoplasms ,medicine.disease_cause ,environment and public health ,medicine ,Humans ,PTEN ,Phosphorylation ,Cyclin-Dependent Kinase Inhibitor p16 ,PI3K/AKT/mTOR pathway ,Aged ,Retrospective Studies ,Aged, 80 and over ,Tissue microarray ,biology ,Kinase ,business.industry ,Smoking ,PTEN Phosphohydrolase ,Middle Aged ,Immunohistochemistry ,Neoplasm Proteins ,enzymes and coenzymes (carbohydrates) ,Eukaryotic Initiation Factor-4E ,medicine.anatomical_structure ,Otorhinolaryngology ,Tissue Array Analysis ,Tonsillar Squamous Cell Carcinoma ,Tonsil ,Carcinoma, Squamous Cell ,biology.protein ,Cancer research ,Female ,Antibody ,Carcinogenesis ,business - Abstract
Background. Expression of p16 is a marker for human papillomavirus (HPV)-related carcinogenesis in head and neck cancer. The purpose of this study is to determine if p16 immunoreactivity is associated with aberrant expression of components of the PI3 kinase pathway. Methods. A tissue microarray (TMA) was constructed for 46 archived tonsillar squamous cell carcinoma specimens. Clinical demographics of these patients were analyzed, and the TMA was interrogated with antibodies directed against p16, phosphorylated AktSer473, phosphorylated S6Ser240/244, phosphorylated S6Ser235/236, phosphorylated 4E-BP1Thr37/46, phosphorylated eIF4ESer209, PTEN, p21, and p53. Results. There was a significant correlation between history of tobacco abuse (>10 pack/years) and absence of p16 expression (p = .01). Expression of p16 was significantly associated with immunoreactivity of p21 (p = .02), PTEN (p = .02), and phosphorylated eIF4E (p = .03). There was no evidence of association between p16 status and expression of phosphorylated S6, phosphorylated 4E-BP1, or p53. Conclusion. p16 positive tonsillar squamous cell carcinoma is characterized by expression of phosphorylated eIF4E that may occur via a mammalian target of rapamycin (mTOR)-independent mechanism. © 2010 Wiley Periodicals, Inc. Head Neck, 2010
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- 2010
18. Viable tumor in postchemoradiation neck dissection specimens as an indicator of poor outcome
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Ian Ganly, Snehal G. Patel, Jatin P. Shah, Diane L. Carlson, Salvatore D'Arpa, Jennifer Bocker, Nancy Y. Lee, Maria Coleman, David G. Pfister, Ganly, I, Bocker, J, Carlson, DL, D'Arpa, S, Coleman, M, Lee, N, Pfister, DG, Shah, JP, and Patel, SG
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Male ,medicine.medical_specialty ,medicine.medical_treatment ,Settore MED/19 - Chirurgia Plastica ,Physical examination ,Kaplan-Meier Estimate ,Article ,medicine ,Carcinoma ,Humans ,chemoradiation ,Laryngeal Neoplasms ,Retrospective Studies ,medicine.diagnostic_test ,business.industry ,Cancer ,Pharyngeal Neoplasms ,Retrospective cohort study ,Neck dissection ,Chemoradiotherapy ,Middle Aged ,Laryngeal Neoplasm ,medicine.disease ,Surgery ,Otorhinolaryngology ,viable tumor ,Positron emission tomography ,Lymphatic Metastasis ,Carcinoma, Squamous Cell ,Neck Dissection ,Female ,prognosis ,business ,Follow-Up Studies - Abstract
Management of the neck in patients treated with primary chemoradiation for cancer of the laryngopharynx with a clinically positive neck remains an area of controversy. The neck may be managed in 1 of 3 ways: by observation, by planned neck dissection, or by salvage neck dissection. Observation of the neck can be done in patients who have a complete or near-complete response to treatment and have a negative positron emission tomography (PET) scan result. Evidence for this approach comes from recent studies that have reported low regional recurrence rates.1–6 Planned neck dissection was carried out in the past in patients with N2 and N3 neck disease irrespective of the response to chemoradiation. The neck dissection was carried out 6 weeks after completion of chemoradiation; this approach had the advantage of carrying out the neck dissection before the onset of fibrosis, thereby making the neck dissection technically similar in complexity to a nonchemoradiation neck dissection. Evidence for a policy of planned neck dissection comes from studies that have shown the presence of tumor in neck dissection specimens in patients who have complete or near-complete radiologic and clinical response in the neck.4,7–10 Before the introduction of fluorodeoxyglucose–positron emission tomography (FDG-PET) scanning, planned neck dissection was a common method for managing the neck after chemoradiation. Some groups still practice this policy because of limitations or unavailability of PET. However, in general, most centers now reserve neck dissection for salvage for residual or recurrent neck disease. Salvage neck dissection is normally carried out if there is clinical or radiologic evidence of neck disease after completion of chemoradiation. Before 2005, our policy was to assess response by clinical examination and CT imaging at 6 to 12 weeks after completion of chemoradiation. However, since 2005, we have been using 18FDG-PET for the assessment of tumor response. The 18FDG-PET is usually carried out at 12 weeks after completion of chemoradiation to minimize any false-positive results from residual inflammation from chemoradiation. Salvage neck dissection in patients who have neck disease as detected by PET is therefore carried out 12 weeks after chemoradiation. This has the disadvantage of making the operation technically more difficult because of the onset of fibrosis. As a consequence, some have advocated the use of selective and superselective salvage neck dissections in these patients.11–14 Clearly there is evidence in the literature to support the practice of planned, as well as salvage neck dissection. However, there is little in the literature that describes what the impact of viable tumor in such neck dissection specimen has on prognosis. In this study, we have examined our own experience of patients undergoing comprehensive neck dissection either as a planned procedure or salvage procedure in the time period before our routine use of PET. The objective was to determine whether viable tumor had a negative impact on prognosis, even after removal of residual tumor by neck dissection.
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- 2010
19. A phase 2 study of pemetrexed plus gemcitabine every 2 weeks for patients with recurrent or metastatic head and neck squamous cell cancer
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Diane L. Carlson, Hilda E. Stambuk, David G. Pfister, Matthew G. Fury, Ronglai Shen, and Sofia Haque
- Subjects
Adult ,Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Guanine ,Phases of clinical research ,Pemetrexed ,Neutropenia ,Deoxycytidine ,Drug Administration Schedule ,Glutamates ,Recurrence ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Clinical endpoint ,medicine ,Humans ,Neoplasms, Squamous Cell ,Neoplasm Metastasis ,Aged ,Aged, 80 and over ,Squamous Cell Carcinoma of Head and Neck ,business.industry ,Carcinoma ,Cancer ,Middle Aged ,medicine.disease ,Gemcitabine ,Tolerability ,Head and Neck Neoplasms ,Response Evaluation Criteria in Solid Tumors ,Carcinoma, Squamous Cell ,Female ,business ,medicine.drug - Abstract
BACKGROUND: Preclinical studies suggest that additive or synergistic effects are achieved with the combination of pemetrexed plus gemcitabine. A phase 1 study of pemetrexed plus gemcitabine given every 2 weeks demonstrated encouraging preliminary efficacy against head and neck squamous cell cancer (HNSCC). METHODS: This was an open-label, single-institution, single-arm, phase 2 study for patients who had received no more than 2 cytotoxic regimens for recurrent and/or metastatic HNSCC. All patients received pemetrexed 500 mg/m2 intravenously plus gemcitabine 1250 mg/m2 intravenously every 2 weeks with vitamin B12 and folate support. The primary endpoint was the objective response rate according to Response Evaluation Criteria in Solid Tumors (RECIST); secondary endpoints were to estimate overall survival and to evaluate safety and tolerability. RESULTS: Twenty-five patients received therapy. All patients had received prior radiotherapy, and half had received prior cytotoxic chemotherapy for recurrent and/or metastatic disease. Neutropenia (grade ≥3) occurred in 24% of patients. Four patients (16%) had a partial response (PR) according to RECIST, and 5 additional patients (20%) had objective tumor reductions of >20 but
- Published
- 2010
20. Prognostic factors of recurrence in salivary carcinoma ex pleomorphic adenoma, with emphasis on the carcinoma histologic subtype: a clinicopathologic study of 43 cases
- Author
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Nancy Y. Lee, Daniel R. Gomez, David S. Klimstra, Nora Katabi, Diane L. Carlson, and Ronald Ghossein
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,Adenoma ,Adenoma, Pleomorphic ,Kaplan-Meier Estimate ,Biology ,Pathology and Forensic Medicine ,Salivary duct carcinoma ,Pleomorphic adenoma ,Carcinosarcoma ,Carcinoma ,medicine ,Humans ,Neoplasm Invasiveness ,Neoplasm Metastasis ,Aged ,Aged, 80 and over ,Myoepithelial cell ,Middle Aged ,Prognosis ,Salivary Gland Neoplasms ,medicine.disease ,Carcinoma ex pleomorphic adenoma ,Female ,Salivary gland neoplasm ,Neoplasm Recurrence, Local - Abstract
Carcinoma ex pleomorphic adenoma is a rare salivary gland neoplasm, especially when the malignant component is only intracapsular/minimally invasive. Moreover, only few studies have assessed the behavior of carcinoma ex pleomorphic adenoma according to the histologic subtype. Forty-three cases of carcinoma ex pleomorphic adenoma were identified over a 27-year period and subjected to a detailed histopathologic analysis. There were 13 intracapsular/minimally invasive and 30 widely invasive carcinomas. There were 15 myoepithelial carcinomas, 25 salivary duct carcinomas, 2 adenocarcinomas not otherwise specified, and 1 carcinosarcoma. There was a trend toward a higher frequency of myoepithelial carcinomas in widely invasive tumors (13/30, 43%) than in intracapsular/minimally invasive (2/13, 15%) carcinoma ex pleomorphic adenoma (P = .095). Adequate follow-up was available for 38 patients. Vascular invasion and distant metastases correlated with decreased disease-free survival and disease-specific survival (P < .05), whereas the extent of invasion and the presence of a high mitotic rate or atypical mitoses correlated with decreased disease-free survival only (P < .05). There was a trend toward worse disease-free survival and disease-specific survival in patients with myoepithelial carcinoma (P = .08). Within the intracapsular/minimally invasive carcinoma ex pleomorphic adenoma group, both myoepithelial carcinoma (2/2, 100%) had metastatic disease, whereas only 1 of 11 nonmyoepithelial carcinoma relapsed (P = .038). Vascular invasion, high mitotic rate, and histologic subtype were found to correlate with recurrence in carcinoma ex pleomorphic adenoma. Patients with intracapsular/minimally invasive tumor have a more favorable outcome than patients with widely invasive neoplasm, but intracapsular/minimally invasive carcinoma ex pleomorphic adenoma can recur and cause death. The presence of myoepithelial carcinoma subtype increases the risk of recurrence in carcinoma ex pleomorphic adenoma, especially within the group of intracapsular/minimally invasive tumors.
- Published
- 2010
21. Adenocarcinoma of the Upper Aerodigestive Tract
- Author
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Vickie Y. Jo, Diane L. Carlson, Edward B. Stelow, and Stacey E. Mills
- Subjects
Pathology ,medicine.medical_specialty ,Esophageal Neoplasms ,business.industry ,Nasopharyngeal Neoplasms ,Adenocarcinoma ,medicine.disease ,Respiratory Tract Neoplasms ,Pathology and Forensic Medicine ,Upper aerodigestive tract ,medicine ,Humans ,Immunohistochemistry ,Basal cell ,Anatomy ,business - Abstract
Although squamous cell carcinoma is the most frequent malignant diagnosis made with upper aerodigestive tract specimens, a myriad of neoplasms can occur throughout the area. Very uncommonly, one encounters adenocarcinomas that cannot be better classified as salivary gland-type neoplasia. This manuscript reviews these tumors, including sinonasal intestinal-type adenocarcinomas, sinonasal low-grade and high-grade nonintestinal adenocarcinomas and nasopharyngeal papillary adenocarcinomas. Clinical, histologic, and immunohistochemical features and differential diagnoses are discussed.
- Published
- 2010
22. SCCRO Promotes Glioma Formation and Malignant Progression in Mice
- Author
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Sarina Bains, Diane L. Carlson, Benjamin J. Golas, Simon G. Talbot, Dolores Hambardzumyan, Duykhanh Pham, Laryssa A. Huryn, Bhuvanesh Singh, Y. Ramanathan, Stephen R. Broderick, Christopher W. Towe, Andrew Kaufman, and Yoshihiro Yonekawa
- Subjects
Cancer Research ,Oncogene ,biology ,Cellular differentiation ,Cell ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,lcsh:RC254-282 ,Molecular biology ,Malignant transformation ,medicine.anatomical_structure ,Glioma ,medicine ,Cancer research ,biology.protein ,PTEN ,Ectopic expression ,Progenitor cell - Abstract
Originally identified as an oncogene activated by amplification in squamous cell carcinomas, several lines of evidence now suggest that squamous cell carcinoma-related oncogene (SCCRO; aka DCUN1D1) may play a role in the pathogenesis of a wide range of human cancers including gliomas. SCCRO's oncogenic function is substantiated by its ectopic expression, resulting in transformation of cells in culture and xenograft formation in nude mice. The aim of this study was to assess the in vivo oncogenicity of SCCRO in a murine model. Ubiquitous expression of SCCRO resulted in early embryonic lethality. Because SCCRO overexpression was detected in human gliomas, its in vivo oncogenic activity was assessed in an established murine glioma model. Conditional expression of SCCRO using a replication-competent ASLV long terminal repeat with splice acceptor/nestin-(tumor virus-A) tv-a model system was not sufficient to induce tumor formation in a wild-type genetic background, but tumors formed with increasing frequency and decreasing latency in facilitated background containing Ink4a deletion alone or in combination with PTEN loss. Ectopic expression of SCCRO in glial progenitor cells resulted in lower-grade gliomas in Ink4a-/- mice, whereas its expression in Ink4a-/-/PTEN-/- background produced high-grade glioblastoma-like lesions that were indistinguishable from human tumors. Expression of SCCRO with platelet-derived growth factor-beta (PDGF-β) resulted in an increased proportion of mice forming glioblastoma-like tumors compared with those induced by PDGF-β alone. This work substantiates SCCRO's function as an oncogene by showing its ability to facilitate malignant transformation and carcinogenic progression in vivo and supports a role for SCCRO in the pathogenesis of gliomas and other human cancers.
- Published
- 2010
23. Paracrine Regulation of Pancreatic Cancer Cell Invasion by Peripheral Nerves
- Author
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Yuman Fong, Jatin P. Shah, Avigail Rein, Sizhi P. Gao, Richard J. Wong, Peter Brader, Ziv Gil, Diane L. Carlson, Oren Cavel, and Kaitlyn J. Kelly
- Subjects
Male ,Cancer Research ,medicine.medical_specialty ,Glial Cell Line-Derived Neurotrophic Factor Receptors ,Immunoblotting ,Nervous System Neoplasms ,Fluorescent Antibody Technique ,Adenocarcinoma ,Mice ,Paracrine signalling ,Transduction, Genetic ,Neurotrophic factors ,Ganglia, Spinal ,Pancreatic cancer ,Internal medicine ,Paracrine Communication ,medicine ,Glial cell line-derived neurotrophic factor ,Animals ,Humans ,Neoplasm Invasiveness ,Glial Cell Line-Derived Neurotrophic Factor ,Nerve Tissue ,RNA, Small Interfering ,Mice, Inbred BALB C ,biology ,Lentivirus ,Proto-Oncogene Proteins c-ret ,Articles ,medicine.disease ,Immunohistochemistry ,Sciatic Nerve ,Pancreatic Neoplasms ,Endocrinology ,Oncology ,Cancer cell ,biology.protein ,RNA Interference ,Sciatic nerve ,Mitogen-Activated Protein Kinases ,Neurotrophin - Abstract
The ability of cancer to infiltrate along nerves is a common clinical observation in pancreas, head and neck, prostate, breast, and gastrointestinal carcinomas. For these tumors, nerves may provide a conduit for local cancer progression into the central nervous system. Although neural invasion is associated with poor outcome, the mechanism that triggers it is unknown.We used an in vitro Matrigel dorsal root ganglion and pancreatic cancer cell coculture model to assess the dynamic interactions between nerves and cancer cell migration and the role of glial cell-derived neurotrophic factor (GDNF). An in vivo murine sciatic nerve model was used to study how nerve invasion affects sciatic nerve function.Nerves induced a polarized neurotrophic migration of cancer cells (PNMCs) along their axons, which was more efficient than in the absence of nerves (migration distance: mean = 187.1 microm, 95% confidence interval [CI] = 148 to 226 microm vs 14.4 microm, 95% CI = 9.58 to 19.22 microm, difference = 143 microm; P.001; n = 20). PNMC was induced by secretion of GDNF, via phosphorylation of the RET-Ras-mitogen-activated protein kinase pathway. Nerves from mice deficient in GDNF had reduced ability to attract cancer cells (nerve invasion index: wild type vs gdnf+/-, mean = 0.76, 95% CI = 0.75 to 0.77 vs 0.43, 95% CI = 0.42 to 0.44; P.001; n = 60-66). Tumor specimens excised from patients with neuroinvasive pancreatic carcinoma had higher expression of the GDNF receptors RET and GRFalpha1 as compared with normal tissue. Finally, systemic therapy with pyrazolopyrimidine-1, a tyrosine kinase inhibitor targeting the RET pathway, suppressed nerve invasion toward the spinal cord and prevented paralysis in mice.These data provide evidence for paracrine regulation of pancreatic cancer invasion by nerves, which may have important implications for potential therapy directed against nerve invasion by cancer.
- Published
- 2010
24. Low-grade Sinonasal Adenocarcinomas
- Author
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Helen P. Cathro, Stacey E. Mills, Diane L. Carlson, Vickie Y. Jo, and Edward B. Stelow
- Subjects
Adult ,Male ,medicine.medical_specialty ,Pathology ,Adolescent ,Adenoma ,Hamartoma ,Nose Neoplasms ,Respiratory Mucosa ,Adenocarcinoma ,S100 protein ,Pathology and Forensic Medicine ,Diagnosis, Differential ,Basal (phylogenetics) ,Paranasal Sinuses ,medicine ,Humans ,Aged ,Aged, 80 and over ,business.industry ,Myoepithelial cell ,Anatomical pathology ,Middle Aged ,medicine.disease ,Immunohistochemistry ,Female ,Surgery ,Anatomy ,business - Abstract
Sinonasal adenocarcinomas (SNACs) are uncommon malignancies that show a variety of growth patterns. These lesions are classified as intestinal or nonintestinal, the latter subclassified as low grade or high grade. We have noted that some low-grade nonintestinal SNACs are associated with respiratory epithelial adenomatoid hamartomas (REAHs), also rare lesions that have recently been shown to be neoplastic. We reviewed 29 nonintestinal low-grade SNACs seen at our institution over a 20-year period, with particular attention to morphology and concomitant REAHs. Nine (31%) low-grade SNACs demonstrated a predominantly exophytic and papillary growth pattern, and 18 (72%) had a more tubular growth pattern. Two (7%) were categorized as "other." Six low-grade tubular SNACs were associated with REAHs. An immunohistochemical panel was performed on 2 of these cases; neoplastic cells were immunoreactive with antibodies to CK7 and S100 protein and nonreactive with antibodies to CK20, similar to other low-grade SNACs. No basal cells or myoepithelial differentiation was seen with immunohistochemical stains for p63 and 34betaE12. This association of low-grade tubular SNACs with REAHs suggests that REAHs may be related to some adenocarcinomas.
- Published
- 2009
25. Tall Cell Variant of Papillary Thyroid Carcinoma without Extrathyroid Extension: Biologic Behavior and Clinical Implications
- Author
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Giovanni Tallini, Diane L. Carlson, Ronald Ghossein, Kepal N. Patel, Nora Katabi, Ashok R. Shaha, Rebecca Leboeuf, B. Singh, Michael Rivera, R. Michael Tuttle, Ghossein R.A., Leboeuf R., Patel K.N., Rivera M., Katabi N., Carlson D.L., Tallini G., Shaha A., Singh B., and Tuttle R.M.
- Subjects
Adult ,Male ,Tall cell ,Pathology ,medicine.medical_specialty ,Time Factors ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Statistical difference ,Thyroid carcinoma ,Endocrinology ,Recurrence ,Chart review ,Carcinoma ,Humans ,Medicine ,Survivors ,Thyroid Neoplasms ,Aged ,Tumor size ,business.industry ,Thyroidectomy ,Genetic Variation ,Middle Aged ,medicine.disease ,Carcinoma, Papillary ,Lymphatic Metastasis ,Risk stratification ,Female ,business - Abstract
The tall cell variant (TCV) is a histologic subtype of papillary thyroid carcinoma (PTC) that is more aggressive than "classical" PTC. Most authors believe that TCV's worse prognosis is related to older age at presentation, larger tumor size, and high frequency of extrathyroid tumor extension (ETE). To assess the biologic and clinical behavior of TCV without ETE, we performed a detailed comparative clinicopathologic analysis of classical PTC and TCV without ETE.TCV was defined as a PTC harboring50% tall cells, while classical PTC was restricted to those tumors containing1% papillae and30% tall cells. Microscopic analysis and chart review identified 62 cases of TCV and 83 classical PTC without ETE. These patients were analyzed for various pathologic, imaging, and clinical parameters including outcome.There was no statistical difference between TCV and classical PTC in relation to age, gender, tumor size, risk stratification, type of therapy, and length of follow-up. TCV displayed more invasion of the tumor capsule and more often infiltrated into the thyroid capsule (p = 0.047 and 0.0004, respectively). Among patients with microscopically assessable regional lymph node (LN), 33 of 49 (67.3%) patients with TCV had LN metastasis at presentation, while only 24 of 60 (40%) classical PTC had positive nodes (p = 0.004). In multivariate analysis, histologic subtype (TCV vs. classical PTC) was the only independent factor associated with LN metastases (p = 0.007). In patients with adequate follow-up, 4 of 62 (6.5%) classical PTC and 7 of the 47 (14.9%) TCV had thyroid cancer recurrence (p = 0.202). TCV recurred at a distant site (3 of 47, 6.4%) while none of the 62 classical PTC developed distant metastases (p = 0.077).TCV without ETE is biologically a more aggressive tumor than classical PTC without ETE independent of age, gender, and tumor size.
- Published
- 2007
26. Sinonasal adenocarcinoma: A rare second malignancy in long term retinoblastoma survivors
- Author
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Pooja Bhagia, Agnes Colanta, Diane L. Carlson, David H. Abramson, Ira J. Dunkel, Dennis H. Kraus, and Ruth A. Kleinerman
- Subjects
Oncology ,Paranasal Sinus Neoplasm ,medicine.medical_specialty ,Retinoblastoma ,business.industry ,medicine.medical_treatment ,Incidence (epidemiology) ,social sciences ,Hematology ,medicine.disease ,Nose neoplasm ,humanities ,eye diseases ,Radiation therapy ,Internal medicine ,Pediatrics, Perinatology and Child Health ,medicine ,Adenocarcinoma ,Sinonasal adenocarcinoma ,business ,human activities ,Unilateral Retinoblastoma - Abstract
Retinoblastoma is the most common primary cancer of the eye in children. The incidence of second tumors in survivors of bilateral retinoblastoma and in survivors of unilateral retinoblastoma who presumably carry a germline RB1 mutation is documented. This paper describes the previously unrecognized association of sinonasal adenocarcinoma as a second malignancy in retinoblastoma survivors. We present three cases who received radiation therapy as a part of their treatment and developed sinonasal adenocarcinoma as a second malignancy. Sinonasal adenocarcinoma should be considered as a second malignancy in retinoblastoma survivors who present with vague sinus symptoms.
- Published
- 2011
27. A comparison of cell cycle markers in well-differentiated lobular and ductal carcinomas
- Author
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Diane L. Carlson, Robert A. Soslow, Marcelo G. Horenstein, and Michael P. Osborne
- Subjects
Cancer Research ,Pathology ,medicine.medical_specialty ,Receptor, ErbB-2 ,Lobular carcinoma ,Breast Neoplasms ,Cell Cycle Proteins ,Biology ,Immunophenotyping ,Metastasis ,Cohort Studies ,Cyclin D1 ,Antigens, Neoplasm ,Proto-Oncogene Proteins ,medicine ,Carcinoma ,Humans ,Neoplasm Invasiveness ,Neoplasm Metastasis ,skin and connective tissue diseases ,neoplasms ,Tumor Suppressor Proteins ,Carcinoma, Ductal, Breast ,Cell Cycle ,Nuclear Proteins ,Antigens, Nuclear ,Proto-Oncogene Proteins c-mdm2 ,Ductal carcinoma ,Cell cycle ,medicine.disease ,Neoplasm Proteins ,body regions ,Carcinoma, Lobular ,Ki-67 Antigen ,Proto-Oncogene Proteins c-bcl-2 ,Receptors, Estrogen ,Oncology ,Immunohistochemistry ,Female ,Tumor Suppressor Protein p53 ,Receptors, Progesterone ,Microtubule-Associated Proteins ,Biomarkers ,Cyclin-Dependent Kinase Inhibitor p27 - Abstract
Infiltrating lobular carcinoma (ILC) and infiltrating ductal carcinoma (IDC) are similar in many respects and their histologic features occasionally overlap. Despite the many similarities, some clinical follow-up data and the patterns of metastasis suggest that ILC and IDC are biologically distinct. Unfortunately, most breast cancer research has focused almost exclusively on the ductal subtype or has not stressed the biologic or molecular genetic distinctions between breast carcinoma subtypes. Several reports have suggested the possibility that ILCs and IDCs differ with respect to expression of antigens involved in proliferation and cell cycle regulation. Therefore, we undertook an immunohistochemical evaluation of cell cycle related antigens in ILCs, including histologic variants thought to represent aggressive neoplasms, and IDCs matched for histologic grade (Modified Bloom-Richardson Grade I). We believe that different antigen expression profiles could elucidate the biological distinctiveness of breast carcinoma subtypes and possibly provide diagnostically relevant information. We studied the expression of the following antigens in 28 archived, formalin-fixed ILCs and 34 well-differentiated IDCs: estrogen receptor (ER), progesterone receptor (PR), Her 2-neu, mib-1, cyclin D1, p27, p53, mdm-2 and bcl-2. 94% of ILCs and 100% of IDCs expressed ER; 75% of ILCs and 76% of IDCs expressed PR; 4% of ILCs and 13% of IDCs expressed c cerb B-2; ILCs and IDCs both expressed mib-1 in approximately 10% of lesional cells; 82% of ILCs and 54% of IDCs expressed cyclin D1; 90% of ILCs and 83% IDCs expressed p27 strongly; 4% of ILCs and 4% of IDCs expressed p53, 25% of ILCs and 33% of IDCs expressed mdm-2; 96% of ILCs and 100% of IDCs expressed bcl-2. None of the apparent differences were statistically significant. The ILC variants demonstrated immunophenotypes that were essentially similar to ILCs of the usual type. We conclude that ILCs and well-differentiated IDCs show similar proliferation and cell cycle control antigen profiles. Despite their unusual histologic features, most ILC variants appear to maintain a characteristic ILC immunophenotype.
- Published
- 2000
28. Management Dilemmas Due to a Paratracheal Follicular Dendritic Cell Tumor
- Author
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Louis Voigt, Stephen M. Pastores, Diane L. Carlson, Ali Hmidi, Robert G. Maki, Neil A. Halpern, and Manjit S. Bains
- Subjects
Adult ,Pulmonary and Respiratory Medicine ,Pathology ,medicine.medical_specialty ,medicine.medical_treatment ,Antineoplastic Agents ,Deoxycytidine ,Bronchoscopy ,Paratracheal ,Humans ,Medicine ,Radiotherapy ,Follicular dendritic cells ,medicine.diagnostic_test ,business.industry ,Sarcoma ,respiratory system ,Airway obstruction ,medicine.disease ,Respiration, Artificial ,Gemcitabine ,Airway Obstruction ,Radiation therapy ,Respiratory failure ,Female ,Stents ,Tracheal Neoplasms ,Surgery ,Cardiology and Cardiovascular Medicine ,Airway ,business ,Dendritic Cells, Follicular - Abstract
Follicular dendritic cell tumors are rare cancers of the lymph nodes of the head and neck. Despite a relatively high rate of recurrence, these neoplasms have a limited impact on the airways because they can be potentially cured by surgical resection. We present the case of a young woman with an unresectable follicular dendritic cell tumor involving the paratracheal region causing upper airway obstruction and respiratory failure. This malignant tumor created numerous management dilemmas and therapeutic challenges related to the unstable airway and the need for tracheal stenting to bypass the airway obstruction.
- Published
- 2006
29. Long-term regional control and survival in patients with 'low-risk,' early stage oral tongue cancer managed by partial glossectomy and neck dissection without postoperative radiation: the importance of tumor thickness
- Author
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Diane L. Carlson, Patrick J. Gullane, Brian O'Sullivan, Jatin P. Shah, Nancy Y. Lee, Snehal G. Patel, Ian Ganly, and David Goldstein
- Subjects
Male ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Disease-Free Survival ,Tongue ,Carcinoma ,medicine ,Humans ,Postoperative Period ,Stage (cooking) ,Neoplasm Metastasis ,Survival rate ,business.industry ,Glossectomy ,Incidence (epidemiology) ,Cancer ,Neck dissection ,Middle Aged ,medicine.disease ,Prognosis ,Surgery ,Tongue Neoplasms ,Survival Rate ,medicine.anatomical_structure ,Oncology ,Lymphatic Metastasis ,Carcinoma, Squamous Cell ,Neck Dissection ,Female ,Neoplasm Recurrence, Local ,business - Abstract
BACKGROUND: The objectives of this study were to determine the incidence of locoregional failure in patients with low-risk, early stage oral tongue squamous cell cancer (OTSCC) who undergo partial glossectomy and ipsilateral elective neck dissection without receiving postoperative radiation. METHODS: A combined database of patients with OTSCC who received treatment at Memorial Sloan-Kettering Cancer Center and Princess Margaret Cancer Center from 1985 to 2005 was established. In total, 164 patients with pathologic T1-T2N0 OTSCC who underwent partial glossectomy and ipsilateral elective neck dissection without postoperative radiation were identified. Patient-related, tumor-related, and treatment-related characteristics were recorded. Local recurrence-free survival, regional recurrence-free survival, and disease-specific survival were calculated by the Kaplan-Meier method. Predictors of outcome were analyzed by univariate and multivariate analysis. RESULTS: At a median follow-up of 66 months (range 1-171 months), the 5-year rates of local recurrence-free survival, regional recurrence-free survival, and disease-specific survival were 89%, 79.9%, and 85.6%, respectively. Regional recurrence was ipsilateral in 61% of patients and contralateral in 39% of patients. The regional recurrence rate was 5.7% for tumors
- Published
- 2012
30. Sinonasal adenocarcinoma: a rare second malignancy in long term retinoblastoma survivors
- Author
-
Pooja, Bhagia, Agnes Basas, Colanta, David H, Abramson, Diane L, Carlson, Ruth A, Kleinerman, Dennis, Kraus, and Ira J, Dunkel
- Subjects
Adult ,Male ,Neoplasms, Radiation-Induced ,Radiotherapy ,Nose Neoplasms ,Infant, Newborn ,Retinoblastoma ,Neoplasms, Second Primary ,social sciences ,Adenocarcinoma ,Middle Aged ,humanities ,eye diseases ,Article ,Humans ,Survivors ,human activities ,Paranasal Sinus Neoplasms ,Aged - Abstract
Retinoblastoma is the most common primary cancer of the eye in children. The incidence of second tumors in survivors of bilateral retinoblastoma and in survivors of unilateral retinoblastoma who presumably carry a germline RB1 mutation is documented. This article describes the previously unrecognized association of sinonasal adenocarcinoma as a second malignancy in retinoblastoma survivors. We present three cases who received radiation therapy as a part of their treatment and developed sinonasal adenocarcinoma as a second malignancy. Sinonasal adenocarcinoma should be considered as a second malignancy in retinoblastoma survivors who present with vague sinus symptoms.
- Published
- 2010
31. Lymph node density is a significant predictor of outcome in patients with oral cancer
- Author
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Snehal G. Patel, Jatin P. Shah, Diane L. Carlson, Ziv Gil, Dennis H. Kraus, Bhuvanesh Singh, Ashok R. Shaha, Richard J. Wong, and Jay O. Boyle
- Subjects
Oncology ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Recurrence ,Internal medicine ,Medicine ,Humans ,Oral Cavity Squamous Cell Carcinoma ,Lymph node ,Survival analysis ,Aged ,Neoplasm Staging ,Aged, 80 and over ,Univariate analysis ,business.industry ,Hazard ratio ,Cancer ,Neck dissection ,Middle Aged ,medicine.disease ,Survival Analysis ,Surgery ,medicine.anatomical_structure ,Treatment Outcome ,Epidermoid carcinoma ,Lymphatic Metastasis ,Neck Dissection ,Female ,Mouth Neoplasms ,Lymph Nodes ,business - Abstract
BACKGROUND: The impact of lymph node metastases on prognosis in patients with oral cavity squamous cell carcinoma (OSCC) has been well recognized. However, accurate stratification of risk for recurrence among patients with lymph node metastases is difficult based on the existing staging systems. In the current study, the utility of lymph node density (LND) was evaluated as an alternative method for predicting survival. METHODS: Three hundred eighty-six patients who underwent neck dissection were included. The median follow-up was 67 months. Five-year overall survival (OS), disease-specific survival (DSS), and locoregional failure (LRF) rates were calculated using the Kaplan-Meier method. LND (number of positive lymph nodes/total number of excised lymph nodes) and tumor-node-metastasis (TNM) staging variables were subjected to multivariate analysis. RESULTS: Using the median (LND = 0.06) as the cutoff point, LND was found to be significantly associated with outcome. For patients with LND ≤0.06, the OS was 58 percent versus 28 percent for patients with LND >0.06 (P 0.06 (P < .001). On univariate analysis, pathologic T and N classification, extracapsular spread, and LND were found to be significant predictors of outcome (P < .001). However, on multivariate analysis, LND remained the only independent predictor of OS (P = .02; hazards ratio, 2.0), DSS (P = .02; hazards ratio, 2.3), and LRF (P = .005; hazards ratio, 4.1). LND was also found to be the only significant predictor of outcome in patients receiving adjuvant radiotherapy (P < .05). Within individual subgroups of pN1 or pN2 patients, LND reliably stratified patients according to their risk of failure (P < .05). CONCLUSIONS: After surgery for OSCC, pathologic evaluation of the neck using LND was found to reliably stratify the risk of disease recurrence and survival. Cancer 2009. © 2009 American Cancer Society.
- Published
- 2009
32. Patterns and incidence of neural invasion in patients with cancers of the paranasal sinuses
- Author
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Amar Gupta, Nancy Y. Lee, Bradford S. Hoppe, Jatin P. Shah, Dennis H. Kraus, Ziv Gil, and Diane L. Carlson
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,Adolescent ,Adenocarcinoma ,Adenoid ,Skull Base Neoplasms ,medicine ,Carcinoma ,Humans ,Neoplasm Invasiveness ,Peripheral Nerves ,Child ,Melanoma ,Aged ,Retrospective Studies ,Aged, 80 and over ,Base of skull ,business.industry ,Incidence (epidemiology) ,Cancer ,General Medicine ,Middle Aged ,medicine.disease ,Carcinoma, Adenoid Cystic ,medicine.anatomical_structure ,Paranasal sinuses ,Otorhinolaryngology ,Carcinoma, Squamous Cell ,Surgery ,Female ,Sarcoma ,business ,Paranasal Sinus Neoplasms - Abstract
To characterize the incidence and pattern of neural invasion (NI) in patients with cancers of the paranasal sinuses and anterior skull base.Retrospective study.A tertiary referral cancer center.The study included 208 patients with cancer of the paranasal sinuses. Patients with brain invasion or neurogenic tumors were excluded.Analysis of clinical and pathologic data on patients with cancer of the paranasal sinuses.Forty-one specimens (20%) had evidence of NI. Sinonasal undifferentiated, adenoid cystic, and squamous cell carcinoma had a high propensity for NI, whereas melanoma and sarcoma rarely invaded nerves. Intraneural invasion was found in 32% of these cases, and 34% invaded more than 1 cm distal to the tumor. Neural invasion was associated with a high rate of positive margins, maxillary origin, and previous surgical treatment (P.04) but not with stage, orbital invasion, or dural invasion. Patients with NI were more likely to undergo adjuvant radiotherapy (P = .003), which significantly improved survival in patients with minor salivary gland carcinomas (P = .04). Multivariate analysis showed that pathologic evidence of NI was not an independent predictor of outcome.Paranasal carcinomas have high propensity for NI, whereas melanoma and sarcoma rarely invade nerves. Patterns of NI include both perineural and intraneural invasion. Neural invasion is associated with positive margins, maxillary origin, and previous surgery.
- Published
- 2009
33. Necrotizing sialometaplasia: a practical approach to the diagnosis
- Author
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Diane L. Carlson
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,Sialometaplasia, Necrotizing ,Necrotizing sialometaplasia ,Diagnostic dilemma ,Salivary Glands ,Pathology and Forensic Medicine ,Diagnosis, Differential ,Mucoepidermoid carcinoma ,Clinical history ,Biopsy ,Carcinoma ,medicine ,Humans ,Basal cell ,Bulimia ,medicine.diagnostic_test ,business.industry ,Calcium-Binding Proteins ,Microfilament Proteins ,Membrane Proteins ,General Medicine ,medicine.disease ,Salivary Gland Neoplasms ,Dermatology ,Medical Laboratory Technology ,Carcinoma, Squamous Cell ,Carcinoma, Mucoepidermoid ,Female ,business ,Biomarkers - Abstract
Context.—Necrotizing sialometaplasia is a benign, self-limited lesion of both major and minor salivary glands, although more commonly the latter. It can represent a diagnostic dilemma and may be mistaken for a malignant neoplasm, such as mucoepidermoid carcinoma, as well as invasive squamous cell carcinoma. A major causal relationship has been ascribed to ischemia. Bulimia, an eating disorder with increasing prevalence in our society, may also be an underlying underreported cause. Objective.—To discuss the potential pathogenesis, diagnostic pitfalls, and the application of immunohistochemistry as an aid in the diagnosis of necrotizing sialometaplasia. Data Sources.—This report uses a previously published case history for illustrative purposes and a review of the current literature. Conclusions.—The diagnosis of necrotizing sialometaplasia may be difficult and is reliant upon a well-oriented biopsy section and a complete clinical history. Diagnosis may be further supplemented via immunohistochemistry, demonstrating focal to absent immunoreactivity for p53, low immunoreactivity for MIB1 (Ki-67), and the presence of 4A4/p63- and calponin-positive myoepithelial cells. Interpreted in context collectively, these findings may be helpful adjuncts in the diagnosis of necrotizing sialometaplasia; nonetheless, to date, hematoxylin-eosin staining remains the gold standard.
- Published
- 2009
34. ALK-positive anaplastic large cell lymphoma in a patient with chronic lymphocytic leukemia
- Author
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Ting Liu, Mai He, Julie Teruya-Feldstein, Cyrus V. Hedvat, and Diane L. Carlson
- Subjects
Male ,Pathology ,medicine.medical_specialty ,CD30 ,Chronic lymphocytic leukemia ,Bone Marrow Cells ,Biology ,Gene Rearrangement, T-Lymphocyte ,Pathology and Forensic Medicine ,Neoplasms, Multiple Primary ,Fatal Outcome ,immune system diseases ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Anaplastic lymphoma kinase ,Humans ,Anaplastic Lymphoma Kinase ,Anaplastic large-cell lymphoma ,Large cell ,Receptor Protein-Tyrosine Kinases ,DNA, Neoplasm ,Middle Aged ,Protein-Tyrosine Kinases ,medicine.disease ,Leukemia, Lymphocytic, Chronic, B-Cell ,Lymphoma ,Leukemia ,Cancer research ,Lymphoma, Large-Cell, Anaplastic ,Surgery ,Lymph Nodes ,Anatomy ,CD5 - Abstract
This article reports the case of a 59-year-old patient with an 8-year history of chronic lymphocytic leukemia (CLL), prostate carcinoma, and squamous cell carcinoma who developed an ALK-positive anaplastic large cell lymphoma (ALCL). Lymph node and bone marrow biopsies showed 2 distinct morphologic populations: ( a) the CLL component showing a diffuse monomorphous infiltrate of small lymphocytes with the typical immunophenotype showing positive CD20, CD5, CD23, and κ light chain restriction and ( b) the ALCL component showing large anaplastic pleomorphic cells positive for CD30, CD45, ALK, CD45Ro, CD4, and vimentin. Polymerase chain reaction performed on the lymph node for immunoglobulin heavy chain and T-cell receptor γ and β showed gene rearrangements after macrodissection of morphologically distinct populations, indicating confirmed genetically distinct populations. Despite intensive chemotherapy, the patient died. This case represents the rare occurrence of an ALK-positive ALCL developing in a patient with CLL.
- Published
- 2008
35. Osteonecrosis of the jaw related to bevacizumab
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Azeez Farooki, Diane L. Carlson, Cherry L. Estilo, Monica Fornier, George C. Bohle, and Joseph M. Huryn
- Subjects
Cancer Research ,Pathology ,medicine.medical_specialty ,Bevacizumab ,Anticorps monoclonal ,medicine.drug_class ,Angiogenesis Inhibitors ,Breast Neoplasms ,Breast pathology ,Monoclonal antibody ,Antibodies, Monoclonal, Humanized ,medicine ,Carcinoma ,Humans ,biology ,business.industry ,Carcinoma, Ductal, Breast ,Osteonecrosis ,Antibodies, Monoclonal ,Middle Aged ,medicine.disease ,Oncology ,Immunology ,Monoclonal ,biology.protein ,Female ,Antibody ,business ,Osteonecrosis of the jaw ,Jaw Diseases ,medicine.drug - Published
- 2008
36. Osteonecrosis of the maxilla and mandible in patients with advanced cancer treated with bisphosphonate therapy
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Jerry Halpern, Catherine Van Poznak, Azeez Farooki, Heiko Schöder, Diane L. Carlson, Cherry L. Estilo, Monica Fornier, Elyn Riedel, George C. Bohle, Tijaana Wiliams, Joseph M. Huryn, Steven J. Tunick, Phyu T. Lwin, and Qin Zhou
- Subjects
Male ,Cancer Research ,medicine.medical_specialty ,Bone disease ,medicine.medical_treatment ,Pamidronate ,Osteoarthritis ,Mandible ,Zoledronic Acid ,Risk Factors ,Internal medicine ,medicine ,Maxilla ,Humans ,Infusions, Intravenous ,Retrospective Studies ,Bone Density Conservation Agents ,Diphosphonates ,business.industry ,Imidazoles ,Osteonecrosis ,Cancer ,Retrospective cohort study ,Bisphosphonate ,medicine.disease ,Jaw Neoplasms ,Surgery ,Zoledronic acid ,Treatment Outcome ,Oncology ,Jaw ,Rheumatoid arthritis ,Female ,business ,Osteonecrosis of the jaw ,medicine.drug - Abstract
Cases of osteonecrosis of the jaw (ONJ) have been reported with an increasing frequency over the past 5 years. ONJ is most often identified in patients with cancer who are receiving intravenous bisphosphonate (IVBP) therapy, but it has also been diagnosed in patients receiving oral bisphosphonates for nonmalignant conditions. To further categorize risk factors associated with ONJ and potential clinical outcomes of this condition, we performed a retrospective study of patients with metastatic bone disease treated with intravenous bisphosphonates who have been evaluated by the Memorial Sloan-Kettering Cancer Center Dental Service between January 1, 1996 and January 31, 2006. We identified 310 patients who met these criteria. Twenty-eight patients were identified as having ONJ at presentation to the Dental Service and an additional 7 patients were subsequently diagnosed with ONJ. Statistically significant factors associated with increased likelihood of ONJ included type of cancer, duration of bisphosphonate therapy, sequential IVBP treatment with pamidronate followed by zoledronic acid, comorbid osteoarthritis or rheumatoid arthritis, and benign hematologic conditions. Our data do not support corticosteroid use or oral health as a predictor of risk for ONJ. Clinical outcomes of patients with ONJ were variable with 11 patients demonstrating improvement or healing with conservative management. Our ONJ experience is presented here.
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- 2008
37. Histologic analysis of angiogenesis and lymphangiogenesis in acellular human dermis
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Bjorn H. Schonmeyer, Paramjeet Singh, Sen Li, Alexander Wong, Babak J. Mehrara, and Diane L. Carlson
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Pathology ,medicine.medical_specialty ,business.industry ,Angiogenesis ,Neovascularization, Physiologic ,Histology ,Rats, Inbred F344 ,Lymphangiogenesis ,Rats ,medicine.anatomical_structure ,Dermis ,medicine ,Animals ,Humans ,Surgery ,Collagen ,business ,Dermal matrix ,Skin - Abstract
Acellular dermal matrix (AlloDerm) is used frequently in a variety of reconstructive procedures. Although it is clear that AlloDerm is revascularized by host tissues, the mechanisms by which vascularization and tissue incorporation occur remain essentially unknown. The purpose of this experiment was to delineate the time course and composition of host cell infiltrate into the matrix of an AlloDerm composite flap.A flap based on the superficial inferior epigastric pedicle in the rat was developed and used to obtain tissue specimens at 3, 7, and 14 days after implantation of AlloDerm. Histology, bromodeoxyuridine incorporation, and immunohistologic assays were used to temporally characterize the appearance of myofibroblasts, endothelial cells, and lymphatic endothelial cells within the matrix.Active host cell proliferation occurs within the matrix at 7 days after implantation. The total number of both host cells and myofibroblasts increased by 8-fold between days 3 and 14. There was a 4-fold increase in endothelial cells between days 3 and 7 but no significant increase at day 14. Putative lymphatic channels were identified within the matrix by 14 days and confirmed using immunohistochemistry for Prox-1, a well-established lymphatic endothelial cell marker.The host response to AlloDerm parallels normal wound healing. Host cell infiltrate increases steadily over a 14-day period. By 7 days after implantation, a large number of CD31 endothelial cells have infiltrated the matrix and early vessels are abundantly present. These vessels continue to mature by day 14. Finally, the authors show that AlloDerm composite flaps also support infiltration and development of a lymphatic network.
- Published
- 2008
38. Mucoepidermoid carcinoma as a secondary malignancy in pediatric sarcoma
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Ronald Ghossein, Dennis H. Kraus, Paul A. Meyers, Mark L. Kayton, Daniel N. Rutigliano, Diane L. Carlson, and Michael P. La Quaglia
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Male ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Bone Neoplasms ,Sarcoma, Ewing ,Mucoepidermoid carcinoma ,medicine ,Carcinoma ,Humans ,Chemotherapy ,Osteosarcoma ,business.industry ,Neoplasms, Second Primary ,General Medicine ,Parotidectomy ,medicine.disease ,Combined Modality Therapy ,Lymphoma ,Surgery ,Parotid gland ,Parotid Neoplasms ,Radiation therapy ,stomatognathic diseases ,medicine.anatomical_structure ,Pediatrics, Perinatology and Child Health ,Carcinoma, Mucoepidermoid ,Female ,Sarcoma ,business - Abstract
Purpose Children diagnosed with osteosarcoma (OS) and Ewing sarcoma (ES) have greatly benefited from the addition of alkylator therapy. However, with greater numbers of long-term survivors, the rising incidence of secondary malignant neoplasms (SMNs) is concerning. Herein we report on 2 patients with sarcoma who developed a case of secondary mucoepidermoid carcinoma after chemotherapy treatment without associated radiation therapy. To our knowledge, this is the first series of mucoepidermoid carcinomas arising in pediatric patients treated for sarcoma without radiotherapy. Methods Long-term survivors of OS and ES currently undergoing routine follow-up care were reviewed and noted for the development of a new secondary malignancy. Details of their initial evaluation, previous therapies, resection techniques, pathologic findings, and follow-up compose this report. Results Two patients, a 17-year-old adolescent boy with OS and 16-year-old adolescent girl with ES, with secondary mucoepidermoid carcinoma of the parotid gland were identified. Both patients underwent primary resection and chemotherapy including alkylating agents, but neither received radiation. The mucoepidermoid carcinomas developed 27 months and 132 months after completion of therapy, respectively, and were noted on routine yearly follow-up. Fine-needle aspiration was nondiagnostic on each, and parotidectomy with preservation of the facial nerve was performed. Pathology revealed low-grade mucoepidermoid carcinoma with tumor extending to the deep margins for both lesions, and radiotherapy to the parotid bed was administered. There were no surgical complications. One patient is alive, without evidence of recurrent mucoepidermoid carcinoma after 4 years; the other recently completed radiotherapy and is disease-free after 12 months. Conclusion Primary mucoepidermoid carcinoma of the parotid gland accounts for less than 10% of all head and neck tumors in childhood. Previous series of secondary mucoepidermoid carcinoma have demonstrated an increased risk in patients with leukemia/lymphoma. This is the first reported series of parotid mucoepidermoid carcinomas occurring after sarcoma treatment without radiotherapy. A common link between the 2 patients may be the use of alkylating therapy.
- Published
- 2007
39. Identification of angiogenesis/metastases genes predicting chemoradiotherapy response in patients with laryngopharyngeal carcinoma
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Ian Ganly, Nicholas D. Socci, Simon G. Talbot, Shaokun Chuai, Bhuvanesh Singh, David G. Pfister, Jatin P. Shah, Ellie Maghami, Dennis H. Kraus, Agnes Viale, Iman Osman, Diane L. Carlson, Ashok R. Shaha, and Eric J. Sherman
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Pathology ,Microarray ,Angiogenesis ,Disease-Free Survival ,Statistics, Nonparametric ,Metastasis ,Neovascularization ,Immunoenzyme Techniques ,Predictive Value of Tests ,Internal medicine ,Complementary DNA ,medicine ,Carcinoma ,Humans ,Neoplasm Metastasis ,Laryngeal Neoplasms ,DNA Primers ,Oligonucleotide Array Sequence Analysis ,Neovascularization, Pathologic ,business.industry ,Reverse Transcriptase Polymerase Chain Reaction ,Gene Expression Profiling ,Pharyngeal Neoplasms ,medicine.disease ,Microarray Analysis ,Gene Expression Regulation, Neoplastic ,Immunohistochemistry ,medicine.symptom ,Neoplasm Recurrence, Local ,business ,Chemoradiotherapy ,Genes, Neoplasm - Abstract
Purpose To identify genes related to angiogenesis/metastasis that predict locoregional failure in patients with laryngopharyngeal cancer (LPC) undergoing chemoradiotherapy (CRT) treatment. Methods Tumor tissue was collected and snap-frozen from 35 sequential patients with histologically confirmed LPC being treated with CRT. Gene expression analysis was performed using a novel cDNA array consisting of 277 genes functionally associated with angiogenesis (n = 152) and/or metastasis (n = 125). Locoregional response was correlated to the gene expression profiles to identify genes associated with outcome. These genes were internally validated by real-time reverse transcriptase polymerase chain reaction (RT-PCR) and validated externally by immunohistochemistry analysis on an independent set of patients. Results Locoregional failure occurred in nine of 35 patients. Seventeen genes from the cDNA microarray correlated with locoregional failure (two-sample t test, P < .05). Seven genes were chosen for additional analysis based on the availability of antibodies for immunohistochemistry. Of these seven genes, real-time RT-PCR validated four genes: MDM2, VCAM-1, erbB2, and H-ras (Wilcoxon rank sum test, P = .008, .02, .04, and .04, respectively). External validation by immunohistochemistry confirmed MDM2 and erbB2 as being predictive of locoregional response. Controlling for stage of disease, positivity for MDM2 or erbB2 was an independent negative predictor of locoregional disease-free survival. Conclusion Genomic screening by cDNA microarray and validation internally by real-time RT-PCR and externally by immunohistochemistry have identified two genes (MDM2 and erbB2) as predictors of locoregional failure in LPC patients treated with CRT. The role of these genes in treatment selection and the functional basis for their activity in CRT response merit additional consideration.
- Published
- 2007
40. Incidence and Prognostic Significance of Perineural Invasion in Patients with Paranasal Sinuses and Skull Base Cancer
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Hilda E. Stambuk, Nancy Y. Lee, Ziv Gil, Amar Gupta, Jatin P. Shah, Dennis H. Kraus, Diane L. Carlson, Mark H. Bilsky, and Bradford S. Hoppe
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Pathology ,medicine.medical_specialty ,business.industry ,Incidence (epidemiology) ,Perineural invasion ,Cancer ,medicine.disease ,Skull ,Paranasal sinuses ,medicine.anatomical_structure ,medicine ,In patient ,Neurology (clinical) ,business ,Base (exponentiation) - Published
- 2007
41. Follicular variant of papillary thyroid carcinoma: a clinicopathologic study of a problematic entity
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Bhuvanesh Singh, Giovanni Tallini, Jeffrey C. Liu, R. Michael Tuttle, Diane L. Carlson, Ronald Ghossein, Nora Katabi, Ashok R. Shaha, Liu J., Singh B., Tallini G., Carlson D.L., Katabi N., Shaha A., Tuttle R.M., and Ghossein R.A.
- Subjects
Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Pathology ,Adolescent ,Noninvasive follicular thyroid neoplasm with papillary-like nuclear features ,Carcinoma, Papillary, Follicular ,Models, Biological ,Thyroid carcinoma ,Diagnosis, Differential ,Adenocarcinoma, Follicular ,medicine ,Carcinoma ,Humans ,Neoplasm Invasiveness ,Thyroid Neoplasms ,Child ,Lymph node ,Aged ,Neoplasm Staging ,business.industry ,Thyroid ,Cancer ,Middle Aged ,medicine.disease ,Adenocarcinoma, Papillary ,medicine.anatomical_structure ,Oncology ,Adenocarcinoma ,Histopathology ,Female ,business - Abstract
There is continuous debate regarding the optimal classification, prognosis, and treatment of the follicular variant of papillary thyroid carcinoma (FVPTC). The objective of this study was to assess the behavior of FVPTC, especially its encapsulated form, and shed more light on its true position in the classification scheme of well differentiated thyroid carcinoma.All patients with FVPTC, follicular thyroid adenoma (FTA), and follicular thyroid carcinoma (FTC) who were diagnosed between 1980 and 1995 were reviewed and reclassified according to the currently accepted definition of FVPTC. The tumors were separated into encapsulated and nonencapsulated (infiltrative/diffuse) types. Encapsulated tumors were subdivided further into tumors with or without capsular/vascular invasion. These different subtypes of FVPTC were correlated with outcome and with other clinicopathologic parameters.After review by 4 pathologists, 78 patients were included in the study. Sixty-one of 78 patients (78%) had encapsulated tumors (18 invasive, 43 noninvasive), and 17 patients had nonencapsulated tumors (infiltrative/diffuse). The gender distribution, age at presentation, and tumor size did not differ between patients with encapsulated and nonencapsulated FVPTC. Patients who had encapsulated FVPTC had a significantly lower rate of marked intratumor fibrosis (18%), extrathyroid extension (5%), and positive margins (2%) compared with patients who had nonencapsulated tumors (88%, 65%, and 50% respectively; P.0001). Regional lymph node metastases were present in 14 of 78 patients (18%), and no patients had distant metastases. The lymph node metastatic rate was significantly higher in patients who had nonencapsulated tumors (11 of 17 patients; 65%) compared with patients who had encapsulated neoplasms (3 of 61 patients; 5%; P.0001). In addition, lymph node metastases were not detected in any noninvasive, encapsulated FVPTCs. With a median follow-up of 10.8 years, only 1 patient developed a recurrence, which occurred in an encapsulated FVPTC that had numerous invasive foci. None of the patients with noninvasive, encapsulated FVPTCs developed recurrences, including 31 patients who underwent lobectomy alone, with a median follow-up of 11.1 years.FVPTC appeared to be a heterogeneous disease composed of 2 distinct groups: an infiltrative/diffuse (nonencapsulated) subvariant, which resembles classic papillary carcinoma in its metastatic lymph node pattern and invasive growth, and an encapsulated form, which behaves more like FTA/FTC. Patients who had noninvasive, encapsulated FVPTCs did not develop lymph node metastases or recurrences and could be treated by lobectomy alone. If the current findings are confirmed, then strong consideration should be given to reclassifying encapsulated FVPTC as an entity that is close to the FTA/FTC class of tumors.
- Published
- 2006
42. Solitary fibrous tumors of the head and neck: a clinicopathologic and radiologic review
- Author
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Hilda E. Stambuk, Mark Edgar, Maria Coleman, Snehal G. Patel, Ian Ganly, Diane L. Carlson, Ronald Ghossein, and Jatin P. Shah
- Subjects
Adult ,Male ,medicine.medical_specialty ,Solitary fibrous tumor ,Soft Tissue Neoplasm ,Neoplasms, Fibrous Tissue ,Mitosis ,Antigens, CD34 ,Soft Tissue Neoplasms ,12E7 Antigen ,Diagnosis, Differential ,Subcutaneous Tissue ,Surgical oncology ,Antigens, CD ,medicine ,Biomarkers, Tumor ,Humans ,Survival rate ,Aged ,business.industry ,Soft tissue ,General Medicine ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,Surgery ,Survival Rate ,Otorhinolaryngologic Neoplasms ,Otorhinolaryngology ,Proto-Oncogene Proteins c-bcl-2 ,Disease Progression ,Histopathology ,Female ,Radiology ,Differential diagnosis ,Positive Surgical Margin ,business ,Tomography, X-Ray Computed ,Cell Adhesion Molecules ,Follow-Up Studies - Abstract
Objective To describe the clinicopathologic and radiologic features of solitary fibrous tumors of the head and neck. Design Retrospective analysis. Setting Tertiary referral center that performs head and neck surgical oncology. Patients Twelve patients with solitary fibrous tumors of the head and neck identified from the pathology and soft tissue tumor databases at Memorial Sloan-Kettering Cancer Center, New York, NY, from 1990 to 2004. All cases were reviewed by 3 experienced pathologists, 1 of whom is an experienced soft tissue tumor pathologist. The diagnosis was confirmed by microscopic features on hematoxylin-eosin staining and by positive staining for CD34 and Bcl2 on immunohistochemical analysis. Tumors were scored for mitotic activity, cellularity, nuclear pleomorphism, necrosis, and the presence of a malignant component. Details on patient characteristics, tumor characteristics, previous treatment and surgery, adjuvant treatment, and outcome were recorded from clinical records. Results Solitary fibrous tumors occurred in patients over a wide age range (27-78 years; median age, 52 years). Seven patients (58%) were women, and 5 (42%) were men. Most tumors presented as a slow-growing painless mass with a duration ranging from 2 months to 5 years. The tumors ranged from 1 × 1 cm to 6 × 5 cm. Patients presented with a subcutaneous mass of the scalp or face in 4 cases, intraoral mass in 4, sinonasal mass in 3, and paraspinal mass in 1. Computed tomographic and/or magnetic resonance imaging scans of 7 of the 12 patients showed well-circumscribed tumors that enhanced strongly with contrast. Treatment for all of the patients was surgical resection. Pathologic findings showed that 9 tumors were benign and 3 were malignant. Three patients had a positive surgical resection margin. All patients were alive at a median follow-up of 8 months (range, 1-76 months). Local recurrence occurred in 1 patient who had positive surgical margins 3 years after the initial surgery. Conclusions Solitary fibrous tumors of the head and neck region are rare and most commonly benign. The diagnosis depends on microscopic and immunohistochemical features, although imaging may help. Patients with these tumors can be safely treated with local excision, but tumors with positive margins require close follow-up over several years owing to the potential for late local recurrence.
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- 2006
43. 18F-FDG PET/CT for detecting nodal metastases in patients with oral cancer staged N0 by clinical examination and CT/MRI
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Heiko, Schöder, Diane L, Carlson, Dennis H, Kraus, Hilda E, Stambuk, Mithat, Gönen, Yusuf E, Erdi, Henry W D, Yeung, Andrew G, Huvos, Jatin P, Shah, Steven M, Larson, and Richard J, Wong
- Subjects
Adult ,Aged, 80 and over ,Male ,Middle Aged ,Magnetic Resonance Imaging ,Fluorodeoxyglucose F18 ,Lymphatic Metastasis ,Positron-Emission Tomography ,Humans ,False Positive Reactions ,Female ,Mouth Neoplasms ,Neoplasm Metastasis ,Tomography, X-Ray Computed ,Aged - Abstract
(18)F-FDG PET has a high accuracy in staging head and neck cancer, but its role in patients with clinically and radiographically negative necks (N0) is less clear. In particular, the value of combined PET/CT has not been determined in this group of patients.In a prospective study, 31 patients with oral cancer and no evidence of lymph node metastases by clinical examination or CT/MRI underwent (18)F-FDG PET/CT before elective neck dissection. PET/CT findings were recorded by neck side (left or right) and lymph node level. PET/CT findings were compared with histopathology of dissected nodes, which was the standard of reference.Elective neck dissections (26 unilateral, 5 bilateral; a total of 36 neck sides), involving 142 nodal levels, were performed. Only 13 of 765 dissected lymph nodes harbored metastases. Histopathology revealed nodal metastases in 9 of 36 neck sides and 9 of 142 nodal levels. PET was TP in 6 nodal levels (6 neck sides), false-negative in 3 levels (3 neck sides), true-negative in 127 levels (23 neck sides), and false-positive in 6 levels (4 neck sides). The 3 false-negative findings occurred in metastases smaller than 3 mm or because of inability to distinguish between primary tumor and adjacent metastasis. TP and false-positive nodes exhibited similar standardized uptakes (4.8 +/- 1.1 vs. 4.2 +/- 1.0; P = not significant). Sensitivity and specificity were 67% and 85% on the basis of neck sides and 67% and 95% on the basis of number of nodal levels, respectively. If a decision regarding the need for neck dissection had been based solely on PET/CT, 3 false-negative necks would have been undertreated, and 4 false-positive necks would have been overtreated.(18)F-FDG PET/CT can identify lymph node metastases in a segment of patients with oral cancer and N0 neck. A negative test can exclude metastatic deposits with high specificity. Despite reasonably high overall accuracy, however, the clinical application of PET/CT in the N0 neck may be limited by the combination of limited sensitivity for small metastatic deposits and a relatively high number of false-positive findings. The surgical management of the N0 neck should therefore not be based on PET/CT findings alone.
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- 2006
44. Prognostic factors of recurrence in encapsulated Hurthle cell carcinoma of the thyroid gland: a clinicopathologic study of 50 cases
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Snehal Patel, Jatin P. Shah, David H. Hiltzik, Ashok Shaha, Ronald A. Ghossein, Robert M. Tuttle, Bhuvanesh Singh, and Diane L. Carlson
- Subjects
Capsular Invasion ,Male ,Cancer Research ,medicine.medical_specialty ,Pathology ,Adenoma ,medicine.medical_treatment ,Thyroid carcinoma ,medicine ,Adenoma, Oxyphilic ,Humans ,Thyroid Neoplasms ,Thyroid cancer ,business.industry ,Thyroid ,Thyroidectomy ,Cancer ,Middle Aged ,medicine.disease ,Prognosis ,Combined Modality Therapy ,medicine.anatomical_structure ,Oncology ,Histopathology ,Female ,Neoplasm Recurrence, Local ,business - Abstract
BACKGROUND Follicular carcinomas of the thyroid gland, including its oncocytic variant (so-called Hurthle cell carcinoma), are subdivided into the indolent encapsulated (“minimally invasive”) and the clinically aggressive widely invasive tumors. There are, however, cases of encapsulated follicular carcinoma that recur and metastasize. Identifying these cases at the time of diagnosis is crucial for prognostic and therapeutic considerations. Because to the authors' knowledge most studies do not focus exclusively on the encapsulated Hurthle cell carcinoma (EHC), the current study attempted to identify predictors of recurrence in EHC. METHODS A tumor was defined as EHC if it was encapsulated, macroscopically well defined with microscopic but no macroscopic evidence of vascular or capsular invasion, and composed of >75% follicular oncocytic cells. Retrospective chart review and microscopic examination identified 50 primary tumors meeting the above criteria at the Memorial Sloan-Kettering Cancer Center between 1967 and 2005. The cases were analyzed for various histologic and clinical parameters. Each parameter was correlated with recurrence-free survival (RFS). RESULTS Seven of 50 (14%) patients developed disease recurrence. All patients who developed recurrence were found to have a high number of foci of vascular invasion (≥ 4). In univariate analysis, ≥ 4 foci of vascular invasion (P 4 cm (P = .049), the presence of mitosis (P = .018), and a solid/trabecular growth pattern (P = .009) were found to be correlated with a decreased RFS. Extensive capsular invasion, gender, and age did not confer a statistically higher recurrence rate. The finding of a solid/trabecular growth and mitosis correlated with the presence of numerous foci (≥ 4) of vascular invasion (P = .01 and P = .005, respectively). CONCLUSIONS A diligent search for vascular invasion is recommended in EHC that display mitosis or a solid/trabecular growth pattern. The presence of ≥ 4 foci of vascular invasion should alert the pathologist and the clinician to a significantly higher risk of recurrence in EHC. Cancer 2006. © 2006 American Cancer Society.
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- 2006
45. Extranodal follicular dendritic cell sarcoma: clinical, pathologic, and histogenetic characteristics of an underrecognized disease entity
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Jennifer Nobrega, Jose G. Guillem, David S. Klimstra, W. Douglas Wong, Wen Chen, Jin Qin, Jinru Shia, Laura H. Tang, and Diane L. Carlson
- Subjects
Adult ,Male ,medicine.medical_specialty ,Pathology ,Adolescent ,Disease ,Pathology and Forensic Medicine ,Pathogenesis ,medicine ,Humans ,Child ,Molecular Biology ,Pathological ,Lymph node ,Aged ,Aged, 80 and over ,Follicular dendritic cells ,business.industry ,Anatomical pathology ,Sarcoma ,Cell Biology ,General Medicine ,Middle Aged ,medicine.disease ,medicine.anatomical_structure ,Follicular dendritic cell sarcoma ,Female ,business ,Dendritic Cells, Follicular - Abstract
It has been more than 10 years since follicular dendritic cell (FDC) sarcoma was first reported to occur in extranodal sites, yet extranodal FDC sarcoma still appears underrecognized, and its clinical and pathological characteristics remain to be defined. This study analyzed the clinical and pathological findings of three such cases that the authors encountered recently and 43 previously reported cases identified in the literature. Assessment of all 46 cases showed a slight female predominance (1.2:1) with a median age of 41.5 years. One-third of the cases were misdiagnosed at initial evaluation mainly because the possibility of FDC sarcoma was not considered. When considered, this disease had distinct pathological characteristics that allowed an accurate diagnosis. Staining for FDC markers, CD21, CD35, and clusterin was particularly helpful. The pathogenesis of the disease appeared heterogeneous, and associated factors included Epstein–Barr virus infection (in hepatic cases) and inflammatory pseudotumor-like conditions. Treatment modality varied widely although surgical resection was often included. With a median follow-up of 18 months, 43% of the cases recurred and 7% died of disease. The 5-year recurrence-free survival was 27.4%. From data available at the current time, we were not able to identify prognostically significant pathologic factors.
- Published
- 2006
46. Poorly differentiated thyroid carcinomas defined on the basis of mitosis and necrosis: a clinicopathologic study of 58 patients
- Author
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Ronald A. Ghossein, David Hiltzik, Shaokun Chuai, B. Singh, Nicole Ishill, Diane L. Carlson, Ashok Shaha, R. Michael Tuttle, and Jatin P. Shah
- Subjects
Oncology ,Microstaging ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Pathology ,Adolescent ,Mitosis ,Disease-Free Survival ,Thyroid carcinoma ,Necrosis ,Poorly Differentiated Thyroid Carcinoma ,Risk Factors ,Internal medicine ,Adenocarcinoma, Follicular ,medicine ,Carcinoma ,Humans ,Neoplasm Invasiveness ,Thyroid Neoplasms ,Neoplasm Metastasis ,Child ,Survival rate ,Thyroid cancer ,Aged ,Neoplasm Staging ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Cancer ,Cell Differentiation ,Middle Aged ,medicine.disease ,Prognosis ,Carcinoma, Papillary ,Survival Rate ,Treatment Outcome ,Adenocarcinoma ,Female ,Neoplasm Recurrence, Local ,business - Abstract
BACKGROUND Poorly differentiated thyroid carcinomas (PDTC) occupy an intermediate position at the prognostic level on the spectrum of thyroid carcinoma progression. However, their histologic definition is controversial. The objective of the current study was to assess the prognostic significance of PDTC defined on the basis of mitosis and necrosis and search for prognostic markers within this group of tumors that are predictive of overall survival (OS) and progression-free survival (PFS). METHODS PDTC was defined as thyroid carcinoma with follicular cell differentiation at the histologic and/or immunohistochemical levels and displaying tumor necrosis and/or ≥ 5 mitoses per 10 high-power fields (×400). Retrospective chart review and microscopic examination identified 58 patients with primary tumors meeting the above criteria and seen at the Memorial Sloan-Kettering Cancer Center between 1992 and 2004. These 58 patients were analyzed for various histologic, clinical, and imaging parameters. Each parameter was correlated with OS and PFS. RESULTS Of the 58 patients studied, 22 (38%) patients died of disease with a 5-year OS rate of 60%. Forty-three of the 58 patients (74%) developed disease recurrence or disease progression, with a 5-year PFS rate of 25%. The median follow-up for the entire patient population was 42.6 months (range, 4–205 mos). A tumor size > 4 cm was found to be correlated with a decreased PFS time (P < 0.001). Those tumors with a capsule demonstrated a significantly improved OS compared with unencapsulated tumors (P = 0.001). The extent of capsular invasion was found to be a significant adverse factor for PFS (P = 0.05). The presence of extrathyroid extension into perithyroid soft tissue was found to be correlated with a decreased OS (P = 0.001) and PFS (P = 0.004). Of 27 patients with distant metastasis, 19 (70%) had concentrated radioactive iodine (RAI) at their metastatic sites. On multivariate analysis, extrathyroid extension and tumor size emerged as the only significant variables in predicting PFS (P = 0.04 and P = 0.01, respectively) whereas extrathyroid extension was found to be the sole independent prognostic factor for OS (P = 0.01). Growth pattern and cell type did not appear to influence outcome. CONCLUSIONS PDTC defined on the basis of mitosis and necrosis constitutes a group of tumors that is more aggressive and homogeneous than PDTC defined by growth pattern. Within this group of patients, microstaging (tumor size, the extent of capsular invasion, and, especially, extrathyroid extension), and not growth pattern or cell type, is able to stratify patients into different prognostic categories. RAI uptake occurs in a significant number of patients with PDTC. Cancer 2006. © 2006 American Cancer Society.
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- 2006
47. Gene expression profiling allows distinction between primary and metastatic squamous cell carcinomas in the lung
- Author
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Bhuvanesh Singh, Pornchai O-charoenrat, Cherry L. Estilo, Valerie W. Rusch, Duy Pham, Inderpal S. Sarkaria, Nicholas D. Socci, Simon G. Talbot, Ivan Ngai, Bernard J. Park, Agnes Viale, Ellie Maghami, Ronald Ghossein, and Diane L. Carlson
- Subjects
Cancer Research ,Pathology ,medicine.medical_specialty ,Lung Neoplasms ,Biology ,Metastasis ,Tongue ,Tongue Carcinoma ,medicine ,Carcinoma ,Cluster Analysis ,Humans ,Oligonucleotide Array Sequence Analysis ,Regulation of gene expression ,Lung ,Gene Expression Profiling ,Reproducibility of Results ,medicine.disease ,Up-Regulation ,Gene expression profiling ,Gene Expression Regulation, Neoplastic ,medicine.anatomical_structure ,Oncology ,Epidermoid carcinoma ,Head and Neck Neoplasms ,Carcinoma, Squamous Cell ,Algorithms - Abstract
Lung neoplasms commonly develop in patients previously treated for head and neck carcinomas. The derivation of these tumors, either as new primary lung cancers or as metastatic head and neck cancers, is difficult to establish based on clinical or histopathologic criteria since both are squamous cell carcinomas and have identical features under light microscopy. However, this distinction has significant treatment and prognostic implications. Gene expression profiling was performed on a panel of 52 sequentially collected patients with either primary lung (n = 21) or primary head and neck (n = 31) carcinomas using the Affymetrix HG_U95Av2 high-density oligonucleotide microarray. Unsupervised hierarchical clustering with Ward linkage and the Pearson correlation metric was performed. To assess robustness, bootstrap resampling was performed with 1,000 iterations. A t test of the normalized values for each gene was used to determine the genes responsible for segregating head and neck from lung primary carcinomas, and those with the most differential expression were used for later analyses. In the absence of a large “test” set of tumors, we used a supervised leave-one-out cross-validation to test how well we could predict the tumor origin. Once a gene expression profile was established, 12 lung lesions taken from patients with previously treated head and neck cancers were similarly analyzed by gene expression profiling to determine their sites of origin. Unsupervised clustering analysis separated the study cohort into two distinct groups which reliably remained segregated with bootstrap resampling. Group 1 consisted of 30 tongue carcinomas. Group 2 consisted of 21 lung cancers and 1 tongue carcinoma. The clustering was not changed even when normal lung or tongue profiles were subtracted from the corresponding carcinomatous lesions, and a leave-one-out cross-validation showed a 98% correct prediction (see Supplementary Data 1). A minimum set of 500 genes required to distinguish these groups was established. Given the ability to segregate these lesions using molecular profiling, we analyzed the lung tumors of undetermined origin. All cases clearly clustered with either lung or tongue tumor subsets, strongly supporting our hypothesis that this technique could elucidate the tissue of origin of metastatic lesions. Although histologically similar, squamous cell carcinomas have distinct gene expression profiles based on their anatomic sites of origin. Accordingly, the application of gene expression profiling may be useful in identifying the derivation of lung nodules and consequently enhances treatment planning.
- Published
- 2005
48. Human papillomavirus DNA and p53 polymorphisms in squamous cell carcinomas from Fanconi anemia patients
- Author
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Bhuvanesh Singh, Jaya M. Satagopan, Diane L. Carlson, Kanan Pujara, Orna Levran, Ivan Ngai, Andy Goberdhan, Leah Ben-Porat, Arleen D. Auerbach, Andrew G. Huvos, Volkert B. Wreesmann, Philip F. Giampietro, Rafaella Diotti, Laryssa A. Huryn, and David I. Kutler
- Subjects
Cancer Research ,Genotype ,Population ,Biology ,medicine.disease_cause ,Polymerase Chain Reaction ,law.invention ,Fanconi anemia ,law ,hemic and lymphatic diseases ,medicine ,Humans ,education ,neoplasms ,Papillomaviridae ,Polymerase chain reaction ,education.field_of_study ,Polymorphism, Genetic ,Bone marrow failure ,Cancer ,medicine.disease ,stomatognathic diseases ,Fanconi Anemia ,Oncology ,Epidermoid carcinoma ,DNA, Viral ,Cancer research ,Carcinoma, Squamous Cell ,Tumor Suppressor Protein p53 ,Carcinogenesis - Abstract
Fanconi anemia is an autosomal recessive disorder characterized by congenital malformations, bone marrow failure, and the development of squamous cell carcinomas (SCCs) and other cancers. Recent clinicopathologic evidence has raised the possibility that an environmental factor such as human papillomavirus (HPV) may be involved in the pathogenesis of SCCs in Fanconi anemia patients. Given the high prevalence of p53 mutations in SCCs among the general population and the lack of p53 mutations in HPV-related carcinogenesis, we evaluated the role of HPV and p53 mutations and polymorphisms in SCC from Fanconi anemia patients. We used polymerase chain reaction (PCR) screening and real-time PCR to detect and quantify HPV DNA in DNA extracted from microdissected SCCs obtained from 24 Fanconi anemia patients (n = 25 SCCs; case subjects) and 50 age-, sex-, and tumor site-matched SCC patients without Fanconi anemia (n = 50 SCCs; control subjects). We PCR-amplified and sequenced exons 4-9 of the p53 gene from SCC DNA. We detected HPV DNA in 84% of the SCC specimens from the case subjects and in 36% of the SCC specimens from the control subjects (P
- Published
- 2003
49. Right Ventricular Myxoma Obstructing the Right Ventricular Outflow Tract
- Author
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Mark Galantowicz, Jeffrey H. Kern, Flor A. Aguilera, and Diane L. Carlson
- Subjects
medicine.medical_specialty ,business.industry ,Heart Ventricles ,Emergency department ,Precordial examination ,Ventricular Outflow Obstruction ,Surgery ,Heart Neoplasms ,Physiology (medical) ,Heart sounds ,Internal medicine ,Heart rate ,cardiovascular system ,Cardiology ,Humans ,Medicine ,Ventricular outflow tract ,Female ,Ventricular Myxoma ,Systolic ejection murmur ,Child ,Cardiology and Cardiovascular Medicine ,business ,Myxoma ,Ultrasonography - Abstract
A12-year-old previously healthy girl developed syncope when walking at school. When she was seen in the emergency department, her heart rate was 115 bpm, the precordial impulse was active, and a thrill was palpated. Third and fourth heart sounds were heard. A grade 4/6 systolic ejection murmur was heard at the …
- Published
- 2000
50. Ureteroscopic biopsy of upper tract urothelial carcinoma: improved diagnostic accuracy and histopathological considerations using a multi-biopsy approach
- Author
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Edmundo Guarnizo, E. Darracott Vaughan, Michael Seiba, Diane L. Carlson, Christian P. Pavlovich, and R. Ernest Sosa
- Subjects
Male ,medicine.medical_specialty ,Ureterectomy ,Urology ,Biopsy ,Ureter ,medicine ,Carcinoma ,Ureteroscopy ,Humans ,Kidney Pelvis ,Aged ,Neoplasm Staging ,Lamina propria ,Carcinoma, Transitional Cell ,Urinary bladder ,medicine.diagnostic_test ,business.industry ,Ureteral Neoplasms ,Reproducibility of Results ,medicine.disease ,Kidney Neoplasms ,medicine.anatomical_structure ,Female ,business ,Renal pelvis - Abstract
We assessed the diagnostic accuracy of a ureteroscopic multi-biopsy approach to upper tract urothelial carcinoma compared with subsequently resected surgical specimens.From 1990 to 1998, 45 upper tract lesions were ureteroscopically evaluated and biopsied with 3Fr cup forceps and/or an 11.5Fr resectoscope before nephroureterectomy or ureterectomy. A definitive diagnosis of urothelial carcinoma was made by biopsy in 40 lesions (89%). Each tumor was histopathologically graded but only staged if the lamina propria were uninvolved (Ta), and if the lamina propria were invaded by tumor (T1+).Of the 40 urothelial tumors 16 (40%) were in the renal pelvis, and 8 (20%) in the proximal and 16 (40%) in the distal ureter. Of the lesions 95% were papillary and 65% were grade 2. Ureteroscopic biopsy grade matched surgical pathological grade in 31 of the 40 cases (78%), and was less than surgical pathological grade in the remainder. Lamina propria was detected in 27 of the 40 biopsies, including 21 of the 34 cup (62%) and all 6 resection loop (100%) biopsies. Ureteroscopic biopsy staging in 27 cases revealed Ta and T1+ disease in 22 and 5, respectively. In the 5 cases in which ureteroscopic biopsy stage was T1+ surgical pathological stage was also pT1+ (range pT1 to pT3). Tumors were pathologically up staged to pT1+ (range pT1 to pT3) in 10 of the 22 cases (45%) in which ureteroscopic biopsy stage was Ta. Tumor location did not affect diagnostic accuracy.This multi-biopsy ureteroscopic approach provided the tissue diagnosis of urothelial carcinoma in 89% of cases and predicted exact histopathological grade in 78%. Although it is not accurate as a staging modality, multi-biopsy ureteroscopy may assess lamina propria invasion in two-thirds of cases.
- Published
- 1999
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