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Squamous cell carcinoma of the vulva (vSCC) is currently categorized either as human papillomavirus (HPV) associated or independent. Immunohistochemical stains, p16INK4a (p16) and p53 are helpful biomarkers to support the designation of vSCC into 1 of the 3 tumor pathways: (1) HPV-associated, (2) HPV-independent, TP53 mutant, or (3) HPV-independent, TP53 wild type. Recently, a framework of p53 expression patterns in vSCC was proposed. In this international and multi-institutional study, we evaluated the interrater agreement for p53 and p16 and tumor pathway classification in a cohort of 50 invasive vSCC across a variety of practice settings (private practice, academic medicine) and levels of expertise (trainees, gynecologic pathologists, dermatopathologists, private practice pathologists). Our study shows that the overall interrater agreement for the interpretation of p16 in vSCC is strong to near perfect, while the agreement for p53 and tumor pathway assignment is overall moderate. Interrater agreement for p53 and tumor pathway is higher (strong) in the academic practice setting. Pathologists without gynecologic subspecialty expertise benefited the most from a brief educational module, which fostered a better understanding and improved comfort level with the p16/p53 stain interpretation and tumor pathway designation in the diagnosis of vSCC. Some interpretative challenges remain, particularly in regard to select p53 patterns and high-risk HPV-in situ hybridization utilization, warranting additional research., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Entrustable professional activities (EPAs) are an educational tool in the framework of competency-based medical education. EPAs are a relatively new concept in pathology. No studies to date exist on the utilization of EPAs during cytopathology fellowship training. This article reviews the recent literature on this topic and shares our institutional experience with the implementation of an EPA for fine needle aspirations and rapid on-site evaluations. While EPAs allow for tracking the competence of the cytopathology fellow toward independent practice for fine needle aspirations and rapid on-site evaluations, the required amount of documentation may represent a potential barrier for the widespread adoption of this new tool., (Copyright © 2024 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Introduction: Limited updated literature exists about the prevalence and spectrum of malignancies involving cerebrospinal fluid (CSF). In this multi-institutional study, we review our experience with focus on first time malignancy diagnosis in CSF samples of adults., Materials and Methods: Institutional databases at 4 academic centers were queried retrospectively for CSFs over a 10-year period. The following data elements were collected: total # of CSFs, total # of CSFs with a malignant diagnosis; for each patient with a first time CSF diagnosis of malignancy: age, gender, diagnosis, prior history of malignancy, and ancillary studies., Results: Twenty-four thousand one hundred forty-two CSFs were collected with a positive for malignancy rate of 2.3% (n = 551). Out of 347 (1.4%) adults with a first-time diagnosis of CSF malignancy 182 (52%) were female (age range: 19-89/mean: 57) and 165 (48%) were male (age range: 20-95/mean: 60). Hematolymphoid malignancies (48%, n = 168) were overall the most common neoplasm. In women, metastatic carcinomas (63%, n = 114) were the leading malignancy, of which the majority were breast primaries. In men, lymphomas/leukemias (64%, n = 106) were the leading malignancy, of which the majority were B-cell lymphomas. Ancillary studies aided the final diagnosis in 110 (32%) cases. For 286 (82%) cases, a prior history of malignancy was available to correlate CSF findings., Conclusions: A malignancy diagnosis in the CSF of adults is rare. The most common malignancies in females and males are metastatic breast carcinoma and hematolymphoid malignancies, respectively. Metastatic neoplasms account for the majority, with primary central nervous system neoplasms being quite uncommon. History of malignancy and ancillary tests can be helpful., (Copyright © 2023 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Tumors of the lung with a spindle cell morphology require consideration of many entities in the differential diagnosis, including metastases. Ancillary immunohistochemical stains but also molecular studies are typically required to arrive at the proper diagnosis. We present a case of a 71-year-old woman with multiple lung nodules, mediastinal lymphadenopathy, and a history of uterine cancer who underwent endobronchial ultrasound-guided fine needle aspiration and biopsy of the lung and mediastinal lymph nodes. A sampling of the lung lesion showed a cytologically bland neoplasm with spindle cell morphology, lacking necrosis or brisk mitotic activity. In conjunction with the cytomorphology, strong and diffuse Transducin-like enhancer of split 1 (TLE1) reactivity in the tumor cells initially raised the diagnosis of synovial sarcoma; however, subsequent results of additional testing showed strong and diffuse expression with AE1/AE3, CK 8/18, TTF-1, synaptophysin and chromogranin and focal or negative staining with a large number of other antibodies. This warranted a diagnosis of a carcinoid tumor. This is the first report of TLE1 staining in a carcinoid tumor of the lung. Therefore, when evaluating tumors of the lung with spindle cell morphology in which the differential diagnosis may include both carcinoid tumor and synovial sarcoma, TLE1 expression should be interpreted with caution and in conjunction with an expanded immunohistochemical staining panel., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Context.—: Vulvar biopsy interpretation and reporting, particularly of vulvar dermatoses, can be challenging in daily practice for both surgical pathologists (SPs) and dermatopathologists (DPs)., Objective.—: To investigate whether prospective consensus reporting of vulvar biopsies by SPs and DPs would provide value and improve overall diagnostic concordance., Design.—: Consecutive vulvar biopsies during a 6-month period were reviewed prospectively by both gynecologic SPs and DPs. Preliminary, independently generated diagnoses were recorded and then shared in consensus review (SPs+DPs). A third pathologist adjudicated cases without consensus. Multiple data elements were collected for each case: division (SP/DP), age, site, clinical history, diagnostic category, preliminary and final (consensus) diagnosis, need for adjudication, ancillary tests, and diagnostic discrepancy., Results.—: Eighty-four biopsies (48 SP, 36 DP) from 70 patients were reviewed. Forty-two of 84 cases (50%) were neoplastic, 38 of 84 (45%) were reactive/inflammatory, with the remaining (5%) showing both or other features. Independent diagnoses were discrepant in 22 of 84 cases (26%), but consensus review resulted in an agreed-upon diagnosis in all cases, with adjudication required in 6 cases. Independent diagnostic agreement increased over time with a reduction in major and minor discrepancies between the first and second half of the study period., Conclusions.—: Prospective review of vulvar biopsies by both SPs and DPs can improve overall reporting. Consensus review allows pathologists to gain diagnostic confidence in interpretation of inflammatory (for SPs) and neoplastic (for DPs) vulvar biopsies; therefore, intradepartmental consultation is of value, particularly in select cases., (© 2020 College of American Pathologists.)

BACKGROUND Cancer in pregnancy is extremely rare, and gastric cancers are rarer still. Diagnosis is difficult in pregnancy due to overlapping symptoms with pregnancy such as nausea, pain, anemia, and fatigue. CASE REPORT A 26-year-old G1 woman at 32 weeks gestation with a past medical history of systemic lupus erythematosus presented with new-onset chest pain and shortness of breath. Computed tomography of the chest, electrocardiogram, and echocardiogram were normal. Laboratory evaluation revealed thrombocytopenia, proteinuria of 480 milligrams, and normal complement. She delivered on hospital day 3 due to worsening chest pain. During cesarean delivery, the patient became hypotensive and hypoxic and required intensive care unit admission after a cesarean hysterectomy. On postoperative day 2 she had a pulmonary embolus and was started on therapeutic anticoagulation. She clinically improved until postoperative day 4, when she was found unresponsive with pulseless electrical activity. After 38 minutes of Advanced Cardiac Life Support, death was pronounced. An autopsy was performed and the cause of death found to be complications of multi-organ system involvement of adenocarcinoma with signet ring cell features. Lymphangitic carcinomatosis was noted throughout the lungs. CONCLUSIONS This patient had adenocarcinoma with signet ring cell features and associated lymphangitic carcinomatosis, which led to her postpartum death. Lymphangitic carcinomatosis is associated with an exceedingly poor prognosis, especially in pregnancy.

Liquid biopsy methodologies, for the purpose of plasma genotyping of cell-free DNA (cfDNA) of solid tumors, are a new class of novel molecular assays. Such assays are rapidly entering the clinical sphere of research-based monitoring in translational oncology, especially for thoracic malignancies. Potential applications for these blood-based cfDNA assays include: (i) initial diagnosis, (ii) response to therapy and follow-up, (iii) tumor evolution, and (iv) minimal residual disease evaluation. Precision medicine will benefit from cutting-edge molecular diagnostics, especially regarding treatment decisions in the adjuvant setting, where avoiding over-treatment and unnecessary toxicity are paramount. The use of innovative genetic analysis techniques on individual patient tumor samples is being pursued in several advanced clinical trials. Rather than using a categorical treatment plan, the next critical step of therapeutic decision making is providing the "right" cancer therapy for an individual patient, including correct dose and timeframe based on the molecular analysis of the tumor in question. Per the 21st Century Cures Act, innovative clinical trials are integral for biomarker and drug development. This will include advanced clinical trials utilizing: (i) innovative assays, (ii) molecular profiling with cutting-edge bioinformatics, and (iii) clinically relevant animal or tissue models. In this paper, a mini-review addresses state-of-the-art liquid biopsy approaches. Additionally, an on-going advanced clinical trial for lung cancer with novelty through synergizing liquid biopsies, co-clinical trials, and advanced bioinformatics is also presented. Impact statement Liquid biopsy technology is providing a new source for cancer biomarkers, and adds new dimensions in advanced clinical trials. Utilizing a non-invasive routine blood draw, the liquid biopsy provides abilities to address perplexing issues of tumor tissue heterogeneity by identifying mutations in both primary and metastatic lesions. Regarding the assessment of response to cancer therapy, the liquid biopsy is not ready to replace medical imaging, but adds critical new information; for instance, through a temporal assessment of quantitative circulating tumor DNA (ctDNA) assay results, and importantly, the ability to monitor for signs of resistance, via emerging clones. Adjuvant therapy may soon be considered based on a quantitative cfDNA assay. As sensitivity and specificity of the technology continue to progress, cancer screening and prevention will improve and save countless lives by finding the cancer early, so that a routine surgery may be all that is required for a definitive cure.

Evaluation of vulvar intraepithelial neoplasia (VIN) may be difficult due to overlapping histologic features seen in both usual (UVIN) and differentiated vulvar intraepithelial neoplasia (DVIN). DVIN represents a diagnostic challenge; poor inter-observer agreement is well documented. P53 has been described as a potentially helpful adjunct in some cases; however, intricacies in its interpretation remain. This study evaluated 41 consecutive cases which consisted of 23 keratinizing dysplasias that were morphologically suggestive of DVIN and 18 UVINs. All cases were stained with p16 and p53. Our results revealed that 22 of 41 (54%) VINs showed novel accentuated wild type (WT) staining with non-linear basal staining for p53, including 12 (52%) cases histologically suggestive of DVIN and 10 (56%) described as UVIN. P16 was positive in 100% of the accentuated wild type cases, consistent with a diagnosis of UVIN. Positive p53 and negative p16 staining was seen in 4 (17%) cases histologically suggestive of DVIN. Of these, 75% progressed to carcinoma, whereas only 1 of 35 (3%) patients with UVIN progressed to carcinoma. In conclusion, DVIN is difficult to diagnose due to potential histologic overlap with UVIN, especially the warty, or keratinizing, subtype. Accentuated WT p53 in absence of concurrent p16 staining may lead to misdiagnosis of DVIN, especially in small biopsy samples. P16/p53 staining should be performed in tandem with strict adherence to patterns considered positive, as patients with UVIN have significantly less risk of progression., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Objectives: Hyalinizing clear cell carcinoma (HCCC) is common in head and neck sites but extremely rare in the lung. This case report describes an HCCC in the lung of a 54-year-old female patient., Methods: We summarize the histomorphologic, immunophenotypic, and molecular features for our and three previously reported HCCCs of the lung with emphasis on potential diagnostic pitfalls., Results: Sections of a well-circumscribed 3.5-cm lung mass were characterized by a bronchocentric tumor growing in sheets, nests, and cords in a background of hyalinized stroma. Tumor cell appearance was clear to eosinophilic, lacking significant pleomorphism or mitotic activity. By immunohistochemistry, the tumor cells were strongly positive with antibodies to pan-keratin, p63, and CK5/6 while negative for CK7, CK20, thyroid transcription factor 1, napsin A, chromogranin, and synaptophysin. Next-generation sequencing demonstrated an EWSR1-ATF1 fusion transcript., Conclusions: Awareness of key morphologic features of pulmonary HCCC is crucial for the recognition of this rare entity in the lung. Ancillary studies, including immunohistochemistry and molecular testing, are essential for the distinction from its mimics., (© American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

A 31-year-old African American man presented for workup of a right hilar and tracheal mass. Stability of the mass when compared with a computed tomographic scan performed 3 years prior suggested an indolent process. On bronchoscopy, there were 2 separate although morphologically similar endobronchial lesions, one in the distal trachea and the second at the level of the right upper lobe bronchus. Biopsies of both lesions demonstrated granular cell tumors. Subsequent rigid bronchoscopy with ablation led to resolution of wheeze, decrease in dyspnea, and documented improvements in both ventilation and perfusion to the right lung. This case illustrates both a rare disease (multifocal endobronchial granular cell tumor) and the physiological impact of reducing large airway obstruction.

Patterns of invasion and stromal response are understudied in vulvar squamous cell carcinoma. The aim of this study was to explore whether histologic features such as an infiltrative pattern of invasion and fibromyxoid stromal response (FMX-SR) are meaningful prognostic factors. We reviewed 143 vulvar squamous cell carcinoma resections and correlated patterns of invasion and stromal response with patient age, ethnicity, depth of invasion, tumor size, perineural invasion (S100/AE1/3 stain), lymph node involvement (LNI), extranodal extension, margin status, pathologic stage, and recurrence. Univariate analyses of continuous variables were performed using t tests, whereas Pearson χ tests were used for categorical variables. Logistic regression analyses examined the relationship between histopathologic characteristics and clinical outcomes. There was a statistically significant association between infiltrative tumors and an FMX-SR in comparison with noninfiltrative tumors (P<0.001). Tumors with FMX-SR were significantly more deeply invasive (P=0.0025) and more likely to have LNI (P=0.0364), extranodal extension (P=0.0227), and perineural invasion (P=0.0011) compared with tumors without FMX-SR. For cases with negative surgical margins, the association between tumors with FMX-SR and LNI was significantly strengthened (odds ratio=4.73, P=0.0042), even after adjustments for age, race, and depth of invasion (odds ratio=4.34, P=0.0154). The presence of both FMX-SR and an infiltrative pattern of invasion in tumors with negative margins was significantly associated with LNI (P=0.0235) and recurrence (P=0.0124). These results suggest that interactions between nerve, tumor, and stromal cells play a role in tumor progression and represent additional prognostic factors that help stratify those patients at highest risk for LNI, extranodal extension, and recurrence.

Objectives: Vulvar squamous cell carcinoma (vSCC) is a gynecologic malignancy diagnosed in nearly 4500 women in the United States each year. Current criteria for treatment planning provide inadequate assessment of aggressive vSCC cases, resulting in insufficient use of adjuvant treatments and high rates of vSCC recurrence. Perineural invasion (PNI) is a pathologic feature inconsistently included in the assessment of vSCC, because its relevance to clinical outcomes in these women is not well defined. The purpose of this study was to determine the association between PNI and relevant clinical parameters such as recurrence., Methods: A total of 103 cases of vSCC were evaluated for PNI using pathology report review and immunohistochemistry dual-chromogen staining for S100 and AE1/3. Medical records were reviewed for clinical and follow-up data. Data were analyzed using univariate and multivariate logistic regression statistical methods., Results: Patients with vSCC containing PNI had a greater risk for cancer recurrence than those whose tumors did not contain PNI (odds ratio=2.8, P=0.0290). There was no significant correlation between the presence of PNI and nodal involvement, stage, or lymphovascular invasion. Tumors with PNI had greater depth of invasion (DOI) (P=0.0047); however, DOI was not associated with recurrence (P=0.2220). When analyzed using a multivariable logistic regression model, PNI was an independent predictor of recurrence in vSCC (adjusted odds ratio=2.613, P=0.045)., Conclusions: PNI is an independent indicator of risk for recurrence in vSCC. The association of PNI with increased risk for recurrence, independent of DOI, nodal involvement, lymphovascular invasion, or stage, should encourage practicing pathologists to thoroughly search for and report the presence of PNI in vSCC.

Background: Historically, recruitment and retention of young women in intervention-based clinical trials have been challenging. In August 2012, enrollment for a clinical trial testing of an investigational human papillomavirus therapeutic vaccine called PepCan was opened at our institution. This study was an open-label, single-arm, single-institution, dose-escalation Phase I clinical trial. Women with recent Papanicolaou smear results showing high-grade squamous intraepithelial lesions or results that could not rule out high-grade squamous intraepithelial lesion were eligible to enroll. Patients with biopsy-confirmed high-grade squamous intraepithelial lesion were also eligible. Colposcopy was performed at the screening visit, and participants became eligible for vaccination when the diagnosis of high-grade squamous intraepithelial lesion was confirmed with biopsy and other inclusion criteria were met. The aim of this study was to identify strategies and factors effective in recruitment and retention of study participants., Methods: Potential vaccine candidates were recruited through direct advertisement as well as referrals, including referrals through the Arkansas telecolposcopy network. The network is a federally funded program, administered by physicians and advanced practice nurses. The network telemedically links rural health sites and allows physician-guided colposcopy and biopsies to be conducted by advanced practice nurses. A variety of strategies were employed to assure good retention, including face-to-face contact with the study coordinator at the time of consent and most of study visits; frequent contact using text messaging, phone calls, and e-mails; and creation of a private Facebook page to improve communication among research staff and study participants. A questionnaire, inquiring about motivation for joining the study, occupation, education, household income, number of children, and number of sexual partners, was administered at the screening visit with the intent of identifying factor(s) associated with recruitment and retention., Results: A total of 37 participants were enrolled between September 2012 and March 2014. The largest proportion of participants (46%) was enrolled from the telecolposcopy network. Others were enrolled through outside institutions (43%), in-house referrals (8%), or direct advertisement (3%). Most participants were motivated to join the study to take care of their health issues. Only two participants joined the Facebook private page. Of the 24 participants who qualified for vaccination, only 1 terminated early due to an unanticipated move., Conclusion: The availability of a large number of potential participants from the telecolposcopy network increased recruitment to this clinical trial by 85% over other traditional means of recruitment. The telecolposcopy network is not only a means of providing a gynecological service to women who otherwise would forego care but also a novel and valuable resource in recruiting participants for a clinical trial., (© The Author(s) 2015.)

Background: There is no widely accepted rapid on-site evaluation (ROSE) reporting system for endobronchial ultrasound-guided transbronchial needle aspiration. At the University of Arkansas for Medical Sciences, ROSE reporting was unstructured. The goal was to evaluate, compare, and improve upon 2 structured approaches proposed in the literature., Methods: One hundred eighteen consecutive nodal aspirates were retrospectively reviewed by a pathology resident and a staff cytopathologist, both of whom were blinded to the original unstructured readings. Each reviewer interpreted every specimen with 2 different structured criteria proposed in the literature: criteria from the University of Minnesota (the Minnesota [MN] criteria) and criteria from the North Shore Long Island Jewish Health System (the New York [NY] criteria). The data allowed a comparison of the original unstructured ROSE system with the MN and NY scoring schemes and the final diagnosis., Results: Original on-site adequacy (OSA) had been assessed at 96%. Three cases were false-adequate according to the original unstructured approach; these had been called adequate on site, but a subsequent slide review including cell blocks did not show definite nodal tissue. OSA dropped to 86% with the MN criteria and to 85% with the NY criteria. No false-adequate on-site diagnoses would have been rendered with the application of either structured criteria. There were no significant differences between the MN and NY criteria with respect to the determination of OSA. An assessment of ease of application favored the NY criteria. With respect to diagnostic categories, each of the systems (MN and NY) was felt to have a category of value not used by the other system., Conclusions: A standardized intra- and inter-institutional system for ROSE reporting is needed. On the basis of comparative analyses and consensus, modifications to prior criteria have been proposed in the hope of approaching this goal., (© 2015 American Cancer Society.)

PURPOSE : Non-surgical treatments for cervical intraepithelial neoplasia 2/3 (CIN2/3) are needed as surgical treatments have been shown to double preterm delivery rate. The goal of this study was to demonstrate safety of a human papillomavirus (HPV) therapeutic vaccine called PepCan, which consists of four current good-manufacturing production-grade peptides covering the HPV type 16 E6 protein and Candida skin test reagent as a novel adjuvant. PATIENTS AND METHODS : The study was a single-arm, single-institution, dose-escalation phase I clinical trial, and the patients (n = 24) were women with biopsy-proven CIN2/3. Four injections were administered intradermally every 3 weeks in limbs. Loop electrical excision procedure (LEEP) was performed 12 weeks after the last injection for treatment and histological analysis. Six subjects each were enrolled (50, 100, 250, and 500 μg per peptide). RESULTS : The most common adverse events (AEs) were injection site reactions, and none of the patients experienced dose-limiting toxicities. The best histological response was seen at the 50 μg dose level with a regression rate of 83% (n = 6), and the overall rate was 52% (n = 23). Vaccine-induced immune responses to E6 were detected in 65% of recipients (significantly in 43%). Systemic T-helper type 1 (Th1) cells were significantly increased after four vaccinations ( P = 0.02). CONCLUSION : This study demonstrated that PepCan is safe. A significantly increased systemic level of Th1 cells suggests that Candida, which induces interleukin-12 (IL-12) in vitro , may have a Th1 promoting effect. A phase II clinical trial to assess the full effect of this vaccine is warranted.

PAX2 has been cited as a technically robust biomarker which nicely delineates precancerous lesions of the endometrium when the endometrial intraepithelial neoplasia (EIN) classification scheme is used. Its utility in distinguishing between atypical and nonatypical hyperplasia when applied within the 1994 World Health Organization classification system is questionable. The purpose of this study was to evaluate PAX2 in a side by side comparison of its staining patterns in a series of endometrial samples that were classified using both systems. A total of 108 precancerous endometrial cases were identified, of which 30 cases were deemed nonhyperplastic by consensus agreement and 11 cases lost the tissue of interest on deeper sections. The remaining 67 cases were categorized according to the 1994 World Health Organization criteria and EIN scheme by 2 gynecologic pathologists. PAX2 staining was scored in lesional tissue as normal or altered (lost, increased, or decreased) compared with nonlesional background. The most common pattern of alteration was complete loss of nuclear PAX2 staining (86.3%) followed by decreased staining (11.3%) and markedly increased staining (2.3%). PAX2 alterations correlated well with EIN diagnoses (33/36, 92%) compared with benign hyperplasia (2/13, 15%) but were less useful when the 1994 World Health Organization classification system was applied (PAX2 alteration in 22/25 (88%) of atypical hyperplasia cases versus 16/25 (64%) of nonatypical hyperplasia cases). Forty-five percent of follow-up hysterectomies with a previous PAX2-altered biopsy case harbored adenocarcinoma. In conclusion, PAX2 may be a helpful adjunct stain and training tool when the features of atypical hyperplasia/EIN are in question.

A histologic pattern-based system of risk stratification for endocervical adenocarcinoma has been recently proposed on the basis of tumor-stroma interface and lymph-vascular invasion. The key utility of the system lies in separating cases with very low risk for nodal metastases (pattern A) from those with higher risk (patterns B and C), which may alter the treatment approach. In this study, we determine the reproducibility of applying this system among gynecologic pathologists from 2 institutions using blinded review of 49 adenocarcinomas from 2003 to 2013. κ values and pairwise differences are calculated for the proposed 3-tier system (patterns A, B, and C) as well as a modified version comparing pattern A versus patterns B and C combined (2-tier system). Consensus diagnosis for the 3-tier system is reached in 50% of cases, with majority of κ values indicating fair to almost perfect agreement (range, 0.24 to 0.84). When condensed to 2 tiers, consensus is reached in 81.3% of cases with κ values showing modest improvement (range, 0.33 to 0.92). Pairwise difference analysis reveals diagnosis trends for specific pathologists on the 3-tier system that decrease with 2 tiers. Interpretive variability may be of practical significance in application of the proposed 3-tier pattern-based approach to endocervical adenocarcinoma. Additional studies with larger patient cohorts are needed to confirm the negligible risk for lymph node involvement seen in pattern A patients and to further evaluate the applicability of this new classification system.

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is widely used for diagnosis of pancreatic lesions. The Echotip Procore Needle (Wilson-Cook Medical) is a new 22G fine biopsy needle (FNB) for obtaining core biopsy material at time of EUS. This study aimed to compare the technical and diagnostic performance of conventional FNA and FNB. Thirty-two patients met the design criteria for this prospective paired cohort study. All lesions sampled were solid (non-cystic) pancreatic masses by EUS appearance. Patients were randomized to receive FNA or FNB by first attempt. A cytopathologist performed on-site evaluations. Samples were assessed for accuracy of diagnosis, cellularity, contamination, and sufficiency for ancillary studies. Technical and diagnostic performances were compared. Compared to FNA, there was a statistically significant decreased ability of FNB to achieve a diagnosis (FNA 93.8%, FNB 28.1%, P < 0.001). FNB was diagnostically superior to FNA in 1 of 32 cases. Technical failures were observed in five cases due to resistance to advancement of the FNB needle. Regarding operator perceived ease-of-use, FNA outperformed FNB (P < 0.001). Eight cases had insufficient FNB material to survive tissue processing. There was no significant difference in mean specimen cellularity between devices. FNA samples showed an increased amount of contaminant (P = 0.036) but were more sufficient for ancillary studies (P = 0.502). Although deemed comparable to FNA when providing material for cytology, the pledged advantage of FNB acting like a core biopsy needle was not apparent in our series. Additional studies are needed before routine adoption of 22G FNB can be recommended., (Copyright © 2014 Wiley Periodicals, Inc.)

Context: Squamous cell carcinoma of the upper aerodigestive tract is a heterogenous entity. Although conventional squamous cell carcinomas are easily recognized, the morphologic variants of squamous cell carcinoma can present a diagnostic challenge. Familiarity with these variants is necessary because many are associated with unique risk factors and are characterized by specific molecular alterations (eg, nuclear protein in testis midline carcinomas). Perhaps the most important distinction is in identifying viral-related from nonviral-related carcinomas. The accurate diagnosis of these variants is necessary for prognostic and therapeutic reasons., Objectives: To provide a clinicopathologic overview and summary of the molecular alterations of the common squamous cell carcinoma variants, including verrucous, spindle cell, acantholytic, adenosquamous, basaloid, and papillary squamous cell carcinoma, as well as nuclear protein in testis midline carcinoma, and to discuss the distinguishing features of human papillomavirus- and Epstein-Barr virus-related squamous cell carcinomas., Data Sources: Published peer-reviewed literature., Conclusions: Familiarity with squamous cell carcinoma variants is essential for proper diagnosis and to guide appropriate clinical management. Further insight into the molecular alterations underlying those variants may lead to alterations in existing treatment approaches and to evolution of novel treatment modalities.

Introduction: Rapid on-site evaluation (ROSE) of fine-needle aspirates is an invaluable teaching tool for a cytopathology (CyP) fellowship. The ability of fellows to accurately perform ROSEs without direct attending supervision is not well documented in the literature. This study reviewed ROSEs performed independently by CyP fellows and focused on diagnostic discrepancies with managerial implications., Material and Methods: All fine-needle aspirates with ROSE documentation performed at the University of Virginia from October 1, 2007 to March 31, 2013 were reviewed and compared with the final diagnosis. Cases were only included if a CyP fellow performed the ROSE. Discrepancy between ROSE and final diagnosis was categorized according to the change. Numbers of false positive (FP) and false negative diagnoses, organ site, and recurrent interpretative pitfalls were noted., Results: CyP fellows performed 6815 ROSEs in 6 years. An attending cytopathologist was present 8% of the time. Of ROSEs without direct attending supervision (6224 fine-needle aspirates), the preliminary and final diagnoses were identical in 95% of cases. FP rate was 1.06%. The most frequent categorical change occurred from ROSE of "atypical" to final diagnosis of "malignant." The most common sites involved in FP diagnoses were pancreas/biliary tract, lung, and lymph node. Experience gained over the fellowship year did not significantly affect the FP rate. Errors encountered are known interpretative challenges., Conclusions: This is the largest study addressing discrepancies between ROSE and final diagnosis and the first study examining CyP fellow performance. Our results affirm that fellows perform extremely well when performing ROSEs independently., (Copyright © 2014 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Objectives: We questioned whether the use of p16(INK4a) immunohistochemistry in endocervical curettage (ECC) specimens would improve the detection of high-grade squamous intraepithelial lesions (HSIL) in a high-risk patient population., Methods: Papanicolaou test results were retrieved in 58 consecutive ECC specimens that were previously diagnosed as no histopathologic abnormality in patients with antecedent HSIL or atypical squamous cells, cannot exclude HSIL. An H&E recut and immunohistochemistry for p16(INK4a) were performed on all cases., Results: HSIL were found in 18 (31%) ECC specimens originally interpreted as negative. Of these 18 cases, three had moderate-sized fragments of ectocervical epithelium with HSIL seen on the recut H&E with concurrent positivity for p16(INK4a). Fourteen cases had rare to occasional clusters of atypical cells with strong immunoreactivity for p16(INK4a). A single case showed a medium-sized fragment of HSIL on the p16(INK4a)-stained section., Conclusions: The use of recuts and adjunct p16(INK4a) should be considered when evaluating ECC specimens in high-risk patient populations.

Esophageal leiomyoma is the most common benign esophageal neoplasm and often presents as an incidental finding or with nonspecific symptoms such as dysphagia or chest pain. Surgical enucleation is the mainstay of treatment and may be accomplished using both open and thoracoscopic approaches. We present a case of a 57-year-old man who presented with a massive circumferential calcified leiomyoma., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)