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Pancreatic ductal adenocarcinoma (PDAC) has one of the poorest prognoses of all malignancies, with a 5-year survival rate

Objectives The microscopic features of urine cytology specimens are subjective and may not reliably distinguish between benign urothelial cells and low-grade urothelial carcinoma (UC). Prior studies demonstrated that keratin 17 (K17) detection in biopsies is highly sensitive for UC. The current study aimed to define K17 diagnostic test performance for initial screening and detect recurrent UC in urine specimens. Methods K17 was detected by immunocytochemistry (ICC) in consecutively collected urine specimens (2018-2019). A qualitative score for the K17 test was determined in 81 samples (discovery cohort) and validated in 98 samples (validation cohort). K17 sensitivity and specificity were analyzed in both cohorts across all grades of UC. Results Based on the discovery cohort, the presence of 5 or more K17 immunoreactive urothelial cells (area under the curve = 0.90; P < .001) was the optimal threshold to define a K17-positive test. The sensitivity of the K17 ICC test for biopsy-confirmed UC was 35 of 36 (97%) and 18 of 21 (86%) in the discovery and validation cohorts, respectively. K17 was positive in 16 of 19 (84%) specimens with biopsy-confirmed low-grade UC and in 34 of 34 (100%) of specimens with high-grade UC. Conclusions K17 ICC is a highly sensitive diagnostic test for initial screening and detection of recurrence across all grades of UC.

BACKGROUND AND AIM: A recently carried out randomized controlled trial showed the benefit of a novel 20-G fine-needle biopsy (FNB) over a 25-G fine-needle aspiration (FNA) needle. The current study evaluated the reproducibility of these findings among expert academic and non-academic pathologists. METHODS: This study was a side-study of the ASPRO (ASpiration versus PROcore) study. Five centers retrieved 74 (59%) consecutive FNB and 51 (41%) FNA samples from the ASPRO study according to randomization; 64 (51%) pancreatic and 61 (49%) lymph node specimens. Samples were re-reviewed by five expert academic and five non-academic pathologists and rated in terms of sample quality and diagnosis. Ratings were compared between needles, expert academic and non-academic pathologists, target lesions, and cytology versus histological specimens. RESULTS: Besides a higher diagnostic accuracy, FNB also provided for a better agreement on diagnosing malignancy (ĸ = 0.59 vs ĸ = 0.76, P

Background Although pancreatic ductal adenocarcinoma (PDAC) has one of the lowest 5-year survival rates of all cancers, differences in survival exist between patients with clinically identical characteristics. The authors previously demonstrated that keratin 17 (K17) expression in PDAC, measured by RNA sequencing or immunohistochemistry (IHC), is an independent negative prognostic biomarker. Only 20% of cases are candidates for surgical resection, but most patients are diagnosed by needle aspiration biopsy (NAB). The aims of this study were to determine whether there was a correlation in K17 scores detected in matched NABs and surgical resection tissue sections and whether K17 IHC in NAB cell block specimens could be used as a negative prognostic biomarker in PDAC. Methods K17 IHC was performed for a cohort of 70 patients who had matched NAB cell block and surgical resection samples to analyze the correlation of K17 expression levels. K17 IHC was also performed in cell blocks from discovery and validation cohorts. Kaplan-Meier and Cox proportional hazards regression models were analyzed to determine survival differences in cases with different levels of K17 IHC expression. Results K17 IHC expression correlated in matched NABs and resection tissues. NAB samples were classified as high for K17 when ≥80% of tumor cells showed strong (2+) staining. High-K17 cases, including stage-matched cases, had shorter survival. Conclusions K17 has been identified as a robust and independent prognostic biomarker that stratifies clinical outcomes for cases that are diagnosed by NAB. Testing for K17 also has the potential to inform clinical decisions for optimization of chemotherapeutic interventions.

Background and Aims Pancreatic cancer organoids are tumor models of individualized human pancreatic ductal adenocarcinoma (PDA), created from surgical specimens and used for personalized treatment strategies. Unfortunately, most patients with PDA are not operative candidates. Creation of human PDA organoids at the time of initial tumor diagnosis is therefore critical. Our aim was to assess the feasibility of creating human PDA organoids by EUS fine-needle biopsy (EUS-FNB) sampling in patients with PDA. Methods In this prospective clinical trial in patients referred to evaluate a pancreatic mass, EUS-FNA was performed for initial onsite diagnosis. Two additional needle passes were performed with a 22-gauge FNB needle for organoid creation. Primary outcome was successful isolation of organoids within 2 weeks of EUS-FNB sampling (P0, no passages), confirmed by organoid morphology and positive genotyping. Results Thirty-seven patients with 38 PDA tumors were enrolled. Successful isolation of organoids (P0) was achieved in 33 of 38 tumors (87%). Establishment of PDA organoid lines for ≥5 passages of growth (P5, five passages) was reached in 25 of 38 tumors (66%). In the single patient with successful P5 FNB sampling–derived and P5 surgically derived organoids, there was identical matching of specimens. There were no serious adverse events. Two patients developed bleeding at the EUS-FNB puncture site requiring hemostasis clips. Conclusions Pancreatic cancer organoids can be successfully and rapidly created by means of EUS-FNB sampling using a 22-gauge needle at the time of initial diagnosis. Successful organoid generation is essential for precision medicine in patients with pancreatic cancer in whom most are not surgically resectable. (Clinical trial registration number: NCT03140592.)

Patient: Female, 54 Final Diagnosis: Primary colonic angiosarcoma Symptoms: Rectal bleeding Medication: Levamlodipine Besylate Clinical Procedure: Hemicolectomy Specialty: Gastroenterology and Hepatology Objective: Rare co-existance of disease or pathology Background: Angiosarcoma is a rare malignant mesenchymal tumor of vascular endothelial cell origin. Its occurrence in the colorectal region is extremely rare. Only 32 cases of primary colorectal angiosarcoma are reported in the current literature. Angiosarcoma in association with calcium channel blocker has been rarely reported. We present such a case of a patient who had been on levamlodipine besylate, a calcium channel blocker, for over 10 years. Case Report: A 53-year-old female with hypertension presented with a fever, a dry cough, and hematochezia. Computed tomography (CT) scan and angiography demonstrated a 6-cm vascular mass in the ileocecal region. The clinical symptoms stopped soon after a right hemicolectomy. The histopathology with immunohistochemical studies confirmed the diagnosis of angiosarcoma. Three months after surgery, the patient had evidence of recurrence of the tumor, however, she no longer presented with a fever or a dry cough. The patient was receiving chemotherapy at the time of the report. Conclusions: Colorectal angiosarcoma is a rare malignancy of endothelial origin with uncertain etiology and often has a poor prognosis. Angiosarcoma seen in a patient taking calcium channel blocker is rare but alarming. CT scan and angiography are helpful tools to raise the suspicion of the diagnosis. A definitive pathological diagnosis relies on histopathology with immunohistochemical stains of endothelial markers. Surgical resection is still the best choice of the different treatment options.

Introduction Although pathology services focused on fine needle aspiration (FNA) biopsy of superficial palpable masses with on-site cytological evaluation are available in a wide range of clinical and academic settings, the addition of ultrasound (US) guidance into FNA practice by a cytopathologist group can be challenging. An US-FNA service provided by a cytopathologist in the department of Pathology is a relatively new practice in the field of medicine. This report summarizes our experience and strategies in achieving this objective and our successful preliminary results. Materials and Methods The US-FNA service includes (1) an FNA procedure to be performed by a cytopathologist under US guidance; (2) onsite adequacy evaluation and diagnosis to be done by the same cytopathologist; and immediate patient consultation and sample triaging carried out by the same cytopathologist in an FNA suite within the department of Pathology. The FNA suite including a procedure room equipped with a portable US machine, an exam/procedure table, a mobile cabinet with FNA supplies, a counter with sink, and a reception room with waiting area is set-up. Results The establishment of the US-FNA service is successful. There is an incremental growth of the service over the first 8 months. Among the 114 cases performed during the first 8 months, the case type distribution is shown to be 50% thyroid nodules, 33% lymph nodes, 5.5% salivary gland masses, 3.5% breast masses, and 8% soft tissue masses. Conclusions The authors' initial 8 months experience and strategies in setting up a new US-FNA practice in a new institution are discussed to highlight obstacles encountered and approaches that promoted the successful establishment of a new service. A conservative approach, focusing on building partnerships with existing clinical services, can be successfully implemented in most institutions, if appropriate strategies are applied. The main strategy is to ensure that the best interests of patients remain the primary focus and that everything possible is done to improve the quality and effectiveness of patient care by providing the best possible diagnostic US-FNA service, to enable optimal clinical management.

Anaplastic dedifferentiation of papillary thyroid carcinoma to lung, pleura and lymph nodes is rare, rapidly progressive and fatal. We report a case of a firefighter who survived the World Trade Center collapse presenting with a large thyroid mass, worsening pleural effusions and pulmonary nodules. A 49-year-old male with history of diabetes and hypertension presented to the Emergency Department with several days of shortness of breath. Vitals were significant for hypoxia, tachypnea and tachycardia. CT Angiography revealed a large (5 x 7 cm) necrotic mass with direct extension to the mediastinum with multiple metastatic lymph nodes in the hila and lungs with bilateral pleural effusions. Dyspnea was relieved in the Emergency Department with placement of a pigtail catheter and pleural fluid was sent for cytology. Further history from family revealed the patient had worked as a firefighter at the World Trade Center for four months. After September 11th, he followed in the WTC survivor clinic in Manhattan with chest x-rays twice a year, the last of which had no abnormalities. Family also reported months of worsening dyspnea with a “high-pitched voice”, weakness and a 20-pound weight loss. Social history was significant for active tobacco use of a pack-per-day for ten years. In the Emergency Department, the patient was placed on supplemental oxygen and otolaryngology performed nasopharyngolaryngoscopy that showed right vocal cord immobility and mild tracheal compression. High-dose dexamethasone taper was initiated. In the hospital, the patient’s respiratory status worsened and he became increasingly septic. Antibiotics were begun for presumed pneumonia. Due to worsening hypercapnea and tracheal compression, the decision was made with family to intubate and vasopressors were begun for hypotension. Interventional radiology performed a biopsy of the thyroid mass revealing papillary carcinoma, but lung nodule biopsy was unrevealing. Subsequent pleural fluid analysis showed poorly differentiated malignant cells with a high degree of nuclear pleomorphism and bizarre shapes suggestive of anaplastic features. Immunohistochemistry was positive for Paired Box Gene 8 (PAX8) and Cytokeratin 7 (CK7). As PAX8 is specific for thyroid cancer, the pleural effusions were thought to be metastatic adenocarcinoma from anaplastic dedifferentiation of papillary thyroid cancer. Given clinical status, the patient was not a candidate for chemotherapy. A goals-of-care decision was made to focus on comfort and the patient passed comfortably with family at bedside. Anaplastic thyroid tumors account for less than two-percent of all thyroid cancers. However, they are rapidly progressive and fatal with tumor burden often doubling in under a week’s time. Identifying these tumors earlier remains a goal in reducing the rate of anaplastic tumors in patients with carcinogenic exposure, such as our patient.

Tophaceous pseudogout is a calcium pyrophosphate dihydrate crystal (CPPD) deposition disease that frequently affects elderly patient in the temporomandibular joint (TMJ). A diagnosis of CPPD deposition disease in the TMJ is challenging due to its mimicking of other benign and malignant entities. Surgical exploration followed by histologic examination is by far the most frequently used diagnostic modality. We present a case of an 87-year-old female who presented with a right TMJ mass. A final diagnosis of tophaceous pseudogout was made on cellular material obtained by ultrasound-guided fine-needle aspiration (US-guided FNA). Based on our case and current available literature, ultrasound-guided FNA is a reliable tool for diagnosing tophaceous pseudogout of the TMJ.

Several studies have compared EUS-guided FNA with fine-needle biopsy (FNB), but none have proven superiority. We performed a multicenter randomized controlled trial to compare the performance of a commonly used 25-gauge FNA needle with a newly designed 20-gauge FNB needle.Consecutive patients with a solid lesion were randomized in this international multicenter study between a 25-gauge FNA (EchoTip Ultra) or a 20-gauge FNB needle (ProCore). The primary endpoint was diagnostic accuracy for malignancy and the Bethesda classification (non-diagnostic, benign, atypical, malignant). Technical success, safety, and sample quality were also assessed. Multivariable and supplementary analyses were performed to adjust for confounders.A total of 608 patients were allocated to FNA (n = 306) or FNB (n = 302); 312 pancreatic lesions (51%), 147 lymph nodes (24%), and 149 other lesions (25%). Technical success rate was 100% for the 25-gauge FNA and 99% for the 20-gauge FNB needle (P = .043), with no differences in adverse events. The 20-gauge FNB needle outperformed 25-gauge FNA in terms of histologic yield (77% vs 44%, P .001), accuracy for malignancy (87% vs 78%, P = .002) and Bethesda classification (82% vs 72%, P = .002). This was robust when corrected for indication, lesion size, number of passes, and presence of an on-site pathologist (odds ratio, 3.53; 95% confidence interval, 1.55-8.56; P = .004), and did not differ among centers (P = .836).The 20-gauge FNB needle outperformed the 25-gauge FNA needle in terms of histologic yield and diagnostic accuracy. This benefit was irrespective of the indication and was consistent among participating centers, supporting the general applicability of our findings. (Clinical trial registration number: NCT02167074.).

Background. Uptake of human papillomavirus (HPV) vaccine in the United States is slow, and the effectiveness of the vaccine has not been assessed in high-risk adolescent populations. Methods. We conducted a longitudinal study of 1139 sexually active, inner-city adolescent women receiving the 3-dose quadrivalent (4vHPV) vaccine. Cervical and anal specimens collected semiannually were tested using an L1-specific polymerase chain reaction assay. Postvaccination incidence of 4vHPV vaccine and nonvaccine HPV types, and risk of cervical cytological abnormalities, were assessed in relation to time to completion of all 3 vaccine doses. Results. Compared to vaccine naive women at enrollment, vaccinated women had significantly lower incidence rate ratios of cervical infection with HPV6/11/16/18 (0.2; 95% confidence interval [CI], .1–.4) and the related types HPV31 and HPV45 (0.4 [95% CI, .2–1.0] and 0.3 [95% CI, .1–.6], respectively), as well as significantly lower incidence rate ratios of anal infection with HPV6/11/16/18 (0.4; 95% CI, .2–.7). Notably, we observed higher risks of cervical HPV6/11/16/18 infection (hazards ratio [HR], 2.9; 95% CI, 1.0–8.0) and associated cytological abnormalities (HR, 4.5; 95% CI, .7–26.0) among women immunized at ≥15 years of age who took ≥12 months (vs

Background Ultrasound (US) guided fine needle aspiration (FNA) biopsy of thyroid are examined and reported by cytopathologists based usually on The Bethesda System for Reporting Thyroid Cytopathology (BTC) regardless of the procedure's performers. This study is designed to determine whether there is any performer-dependent difference. Methods Six hundred and fifty-one thyroid US-FNAs in correlation with surgical follow-up (SFU) were studied. The statistical analysis was performed using the surgical pathology diagnosis as the gold standard. Results Among the 283 cases performed by cytopathologists, there were 8 (2.8%) nondiagnostic (BTC I), 197 (69.6%) benign (BTC II), 31 (11%) atypical (BTC III), 14 (5%) suspicious for follicular neoplasm (BTC IV), 12 (4.2%) suspicious for malignancy (BTC V), and 21 (7.4%) positive for malignancy (BTC VI), and there were 55 (19.4%) cases with SFU. The 368 cases performed by others showed 76 (21%) BTC I, 238 (65%) BTC II, 26 (7%) BTC III, 10 (3%) BTC IV, 9 (2.5%) BTC V 5, and 9 (2.5%) BTC VI, and there were 26 (7%) cases with SFU. The cytopathologist group achieved better sensitivity (91.3 vs.78%); slightly better specificity (83.3 vs. 82%); better positive predictive value (87.5 vs. 70%); similar negative predictive value (88.2 vs. 88%); and better overall accuracy (87.8 vs. 81%) compared with the non-cytopathologist group. Overall the difference for all statistical values is significant different (P = 0.041). Conclusion US-FNA performed by cytopathologists showed a lower unsatisfactory rate and significantly better overall statistical values. Cytopathologists may play an important role in thyroid patient care. Diagn. Cytopathol. 2016;44:787–791. © 2016 Wiley Periodicals, Inc.

We report an extremely rare case of skin collision tumor between primary Merkel cell carcinoma (MCC) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) first diagnosed on ultrasound-guided fine-needle aspiration biopsy (US-FNA). A 95-year-old female with a history of CLL presented with a slow growing left malar mass was referred to our clinic for US-FNA. US scan showed a well-defined subcutaneous mass (2.78 cm) with complex echogenicity. On-site assessment showed a cellular aspiration which was interpreted as small blue round cell tumor. On further examination, smears and cell block showed dimorphic populations of relatively larger cells with neuroendocrine features and smaller lymphoid cells. Immunocytochemical studies of cell block sections revealed that the larger cells were positive for CD56, Chromogranin, Synaptophysin, CK8/18, CK20 (dot-like pattern); and the smaller cells were positive for CD45. Flow cytometric analysis showed a majority of CD16/CD56 positive cells, 17% of monoclonal B-cells, and 14% of reactive T cells. The immunophenotype of the monoclonal B cells were of CLL/SLL. The diagnosis of a collision tumor composed of primary MCC and CLL/SLL was confirmed. Surgical resection of the mass one month later concurred with the FNA cytological diagnosis. The fact that surgical specimen displayed a solid tumor with both CLL/SLL and MCC components ruled out the possibility that the FNA merely had MCC with peripheral leukemic blood contaminant. No additional MCC lesion was found in the patient, which ruled out the possibility of metastatic MCC to a lymphomatous lymph node.

Ultrasound-guided fine needle aspiration (USG-FNA) has enabled cytopathologists to accurately diagnose smaller or non-palpable lymph nodes (LN) on a regular basis. Pre-FNA clinical and ultrasonographic factors, such as a patient's age, ratio of short to long axis diameter (S/L ratio), internal echogenicity, and the vascular pattern of a LN, are reported to be able to predict the benign or malignant nature of a LN. This study is designed to test the formula “0.06 × (age) + 4.76 × (S/L ratio) + 2.15 × (internal echo) + 1.80 × (vascular pattern)” generated from the study of Liao et al. as a scoring system for predicting LN malignancy in a cytopathologist operated USG-FNA practice. Eighty-three reports of USG-FNA of LNs issued between 7/1/2008 and 4/28/2010 were reviewed. Patient's age, S/L ratio, internal echo, and vascular pattern were used to generate scores based on the aforementioned formula. A score of seven was used as a cutoff for predicting benign ( 7) LNs. FNA cytology diagnosis, flow cytometric analysis as well as subsequent surgical diagnosis in some cases served as gold standard for statistical analysis. Among 46 USG-FNA of LNs with scores > 7, 38 were malignant and eight were benign. All 37 USG-FNA of LNs with scores < 7 were proven to be benign. The scoring system achieved 100% sensitivity, 82% specificity, 83% positive predictive value, 100% negative predictive value, and 90% accuracy. Further study of the eight “false-positive” cases revealed that three of them (37.5%) were found to be malignant in follow-up FNA and/or surgical biopsy. This scoring system may serve as a complementary tool in determining how aggressive a FNA procedure should be performed, how a FNA sample of LN should be triaged for ancillary study, and how closely a patient with lymphadenopathy should be followed up. Diagn. Cytopathol. 2013;41:1100–1106. © 2011 Wiley Periodicals, Inc.

Background The incidence of esophageal adenocarcinoma is rapidly increasing and is now one of the leading causes of cancer death in the western world. MicroRNAs (miRNAs) are small noncoding RNAs that regulate the expression of protein-encoding genes and are involved in the development, progression and prognosis of other malignancies. We hypothesized that global miRNA expression would predict survival and lymph node involvement in a cohort of surgically resected esophagus cancer patients. Methods The miRNA analysis was performed using a custom Affymetrix microarray with probes for 462 known human, 2,102 predicted human, 357 mouse, and 238 rat miRNAs. Expression of miRNA was evaluated in 45 primary tumors, and the association of miRNA expression with patient survival and lymph node metastasis was assessed. The prognostic impact of identified unique miRNAs was verified with quantitative reverse transcriptase polymerase chain reaction. Results Our data indicate that the expression of individual human miRNA species is significantly associated with postresection patient survival. Using data from five unique miRNAs, we were further able to generate a combined miRNA expression signature that is associated with patient survival ( p = 0.005; hazard ratio 3.6) independent of node involvement and overall stage. The expression of three miRNAs (miR-99b and miR-199a_3p and _5p) was also associated with the presence of lymph node metastasis. Conclusions These results suggest miRNA expression profiling could provide prognostic utility in staging esophagus cancer patients and treatment planning with endoscopic and neoadjuvant therapies. The alterations of specific miRNAs may further elucidate steps in the metastatic pathway and allow for development of targeted therapy.

Hepatocellular carcinoma (HCC) is a highly malignant neoplasm, often presenting at late stage and portending a poor prognosis for the patient. The peripancreatic fat is a rare site of extrahepatic metastasis, and metastatic HCC can mimic primary pancreatic neoplasms, even in this location. It is crucial to be aware of this pitfall in the evaluation of aspiration cytology of pancreatic neoplasms and to develop a strategy to reach the correct diagnosis. We present an endoscopic ultrasound fine-needle aspiration diagnosis of metastatic HCC presenting as a pancreatic mass radiologically that had neuroendocrine features on various cytological and histological preparations. The metastatic lesions were located surgically in the peripancreatic adipose tissue with involvement of one peripancreatic lymph node. This case illustrates the utility of FNA for diagnosing uncommon presentations of HCC and the importance of clinical history, cell block, and an immunocytochemical panel in determining the origin of the tumor. Diagn. Cytopathol. 2009. © 2009 Wiley-Liss, Inc.

Context After the collapse of the World Trade Center (WTC) on 11 September 2001, a dense cloud of dust containing high levels of airborne pollutants covered Manhattan and parts of Brooklyn, New York. Between 60,000 and 70,000 responders were exposed. Many reported adverse health effects. Case presentation In this report we describe clinical, pathologic, and mineralogic findings in seven previously healthy responders who were exposed to WTC dust on either 11 September or 12 September 2001, who developed severe respiratory impairment or unexplained radiologic findings and underwent video-assisted thoracoscopic surgical lung biopsy procedures at Mount Sinai Medical Center. WTC dust samples were also examined. We found that three of the seven responders had severe or moderate restrictive disease clinically. Histopathology showed interstitial lung disease consistent with small airways disease, bronchiolocentric parenchymal disease, and nonnecrotizing granulomatous condition. Tissue mineralogic analyses showed variable amounts of sheets of aluminum and magnesium silicates, chrysotile asbestos, calcium phosphate, and calcium sulfate. Small shards of glass containing mostly silica and magnesium were also found. Carbon nanotubes (CNT) of various sizes and lengths were noted. CNT were also identified in four of seven WTC dust samples. Discussion These findings confirm the previously reported association between WTC dust exposure and bronchiolar and interstitial lung disease. Long-term monitoring of responders will be needed to elucidate the full extent of this problem. The finding of CNT in both WTC dust and lung tissues is unexpected and requires further study.

One of the major handicaps in contemporary clinical oncology is the inability to predict the responsiveness of any individual's malignancy to specific therapies. The purpose of this study was to test the feasibility of immunocytochemically detecting markers that may be affected by therapy or are predictive of therapeutic responsiveness, including phosphohistone H1 (anti-p-H1 MoAb 12D11) and X-linked inhibitor of apoptosis (XIAP) in small samples obtained via fine-needle aspiration (FNA) biopsy procedure, thus improving therapeutic monitoring. p63, a squamous stem cell regulatory protein, was also examined. These three markers were studied in FNA cell block samples of head and neck squamous cell carcinoma (HNSCC). Twenty-eight alcohol-fixed formalin-postfixed paraffin-embedded cell-block samples from FNAs of patients with HNSCC were subjected to antigen retrieval and then incubated with anti-XIAP, anti-p-H1, and anti-p63, and developed using EnVision-Plus reagents and diaminobenzidine as chromagen; Granular or heterogeneous cytoplasmic staining for XIAP and nuclear staining for p63 and p-H1 were considered positive. Among the 28 cases studied, the overall positive rates for XIAP, p-H1, and p63 were 60.7%, 96.4%, and 92.8%, respectively. The staining intensity for XIAP: + 70.6%, ++ 23.5%, +++ 0%, and ++++ 5.9%; for p-H1: + 48.1%, ++ 11.1%, +++37.0%, and ++++ 3.7%; and for p63: + 11.5%, ++ 23.1%, +++ 53.9%, and ++++ 11.5%. The expression of p-H1 and p63 appeared to be higher and stronger than that of XIAP in HNSCC. This study demonstrated the feasibility of monitoring expression of three tumor markers using FNA samples. p-H1 and XIAP may be useful for monitoring actions of cyclin-dependent kinase inhibitors, XIAP-lowering, and/or apoptosis-inducing drugs, respectively. Future studies will focus on the impact of therapies upon these staining profiles.

Background X-linked inhibitor of apoptosis protein (XIAP) is a member of the inhibitor of apoptosis proteins family of caspase inhibitors. Expression of XIAP in various neoplasms has been associated with aggressive behavior. The biological progression from pleomorphic adenoma (PA) to carcinoma ex pleomorphic adenoma (CXPA) has been poorly understood. We studied XIAP expression by immunohistochemistry in PA and CXPA. Materials and methods Formalin-fixed, paraffin-embedded representative sections of 14 cases of PA and seven cases of CXPA (four invasive and three intracapsular) were stained with anti-XIAP (# 610763; BD Biosciences, San Jose, CA, USA) following citrate-based antigen retrieval. Granular cytoplasmic staining was considered positive and intensity was assessed from weak (1+) to strong (3+). PAs were morphologically evaluated for cellularity, cytological atypia and mitotic activity. Results Of the seven PAs composed mostly of myxohyaline stroma with scattered ductal elements, two tumors showed no staining and five showed rare ( Conclusion Increased expression of XIAP from PA to cellular PA to CXPA and in atypical cells within cellular areas of PA adds to our growing understanding of defective apoptotic pathways in malignant transformation in this group of salivary gland tumors and suggests an adenoma to adenocarcinoma model of progression. Further correlation with other oncogene expression may provide insight into the multiple molecular pathways that are affected in these tumors. Targeted therapy of XIAP may play a future role in the management of CXPA.

The family of AKT kinases, AKT-1, 2, and 3, collectively play a crucial role in key processes, as well as pathologic processes such as oncogenesis. The numerous AKT phosphorylation targets include proteins essential to the regulation of cell cycling, protein translation, suppression of programmed cell death, all of which, upon activation via AKT-mediated phosphorylation, promote tumor growth, survival, and aggressiveness. Activation of the AKT pathway can be immunohistochemically detected with antibodies that specifically react with phosphorylated or nonphosphorylated forms of AKT. The following review summarizes the use of phospho-AKT immunohistochemistry as a potentially valuable tool in cancer prognostication in a wide spectrum of common and uncommon malignancies, including squamous carcinoma of cervix and of head and neck; adenocarcinoma of endometrium, ovarian, breast, prostate, kidney, colon, and pancreas; carcinomas of lung and thyroid; and hematopoietic, soft tissue, and central nervous system neoplasms. To date, the findings overall suggest that the major use of p-AKT immunohistochemical staining lies in prognostication and possibly in individualization of therapy rather than in differential diagnosis.

Fine needle aspiration (FNA) biopsy is a useful tool in the diagnosis and management of suspicious masses. Most FNA biopsies of palpable masses can be performed without radioguidance by either clinicians or cytopathologists; however, it is unclear if there is a difference in the diagnostic yield of the procedure based on who performs the FNA. We reviewed the FNA biopsy results of 200 patients presenting with head and neck masses to a tertiary care center from 2003 to 2004. One hundred FNA biopsies were performed by clinicians and 100 performed by cytopathologists. Seventy-one underwent subsequent surgical biopsy or definitive surgery. Results of the FNA biopsies performed by the clinicians and the cytopathologists were compared based on the percentages of FNAs that were diagnostic, suspicious/suggestive, and nondiagnostic. Additionally, the pathology results of the 71 surgical biopsies or resections were compared with the preoperative FNA results. Of the 100 FNA biopsies performed by cytopathologists, 83% were diagnostic, 10% were suspicious/suggestive, and 7% were nondiagnostic. Of the 100 FNA biopsies performed by clinicians, 24% were diagnostic, 43% were suspicious/suggestive, and 33% were nondiagnostic. Cytopathologists achieved significantly better results (P

The p53 homologous squamous stem-cell regulatory protein p63 is expressed in squamous carcinomas but is not characteristically detected in small-cell carcinomas (SCCs). A panel of thyroid transcription factor (TTF) 1 and p63 has been shown to be useful in distinguishing SCCs from poorly differentiated squamous carcinoma of the lung (PDSLC) in small biopsies and cytological cell blocks. Because tumor samples frequently are limited to cytological smears, we attempted to detect p63 in destained slides from a spectrum of pulmonary malignancies. Archival alcohol-fixed smears from 60 cases of cytologically diagnosed malignancies in bronchoscopically (n = 59) or fine-needle aspiration-obtained specimens (n = 1) were destained in acid alcohol, postfixed in 10% formalin, subjected to citrate-based antigen retrieval, and immunostained by exposure to anti-p63 monoclonal antibody 4A4, followed by reagents from a streptavidin-biotin immunoperoxidase kit, and diaminobenzidine as the chromogen. Postfixation in 10% formalin was found to be necessary for immunostaining. Normal ciliated and goblet cells were p63 negative, but reserve cells were p63 positive. All cases of squamous-cell carcinoma were positive for p63. Of 10 tumor samples originally diagnosed as SCC, only 6 samples were p63 negative and 4 samples exhibited positive staining. However, proper interpretation of the immunohistochemical (IHC) staining pattern and careful scrutiny of the cytological features and biopsy specimens in three of four cases led us to reclassify three cases into PDSLC. All adenocarcinomas (ACAs; n = 12), large-cell carcinomas (n = 4), and metastatic ACAs (n = 5) were p63 negative. Positive staining was seen in 9/16 tumors designated as non-SCCs; these tumors were not classified further into distinct histological categories. p63 staining in destained slides may be of value in facilitating the differential diagnosis between PDSLC and SCC. Criteria for conservative interpretation of results are discussed and include examination of reserve cells and ciliated cells on the same slide as internal positive and negative controls. Diagn. Cytopathol. 2005;32:198–203. © 2005 Wiley-Liss, Inc.

Objective To describe the detection of collagen balls in peritoneal washings over a 10-year period, revealing an unexpected and unexplained higher incidence than in the past. Study design Reports of routinely processed, Papanicolaou-stained smears and cytospins and hematoxylineosin-stained cell blocks from peritoneal washes and ascitic fluids seen over an 8-year period (1995-2002) were reviewed, and the percentage of specimens in which collagen balls were noted was determined. To rule out a learning curve phenomenon, the first 100 consecutive peritoneal washings and ascitic specimens from years 1993-2001 plus 2002 were rescreened, and the percentage of specimens containing collagen balls was determined. Results The percentages of cases with collagen balls increased steadily beginning with 8 of 467 cases (3.2%) in 1995 to 185 of 650 (28.5%) in 2002, as reported in the case records. Rescreened cases also showed a similar increase, 4.0% in 1993 to 29% in 2002. No procedural modifications were made in specimen processing during this interval, nor are we aware of any procedural change in obtaining cytologic samples. Conclusion An unexplained 7-fold increase in the percentage of peritoneal samples with collagen balls occurred over a 10-year period. This increase cannot be attributed to changes in specimen handling or to a learning curve phenomenon. This finding is of unknown significance and may warrant further investigation.

We studied the usefulness of p63 and thyroid transcription factor–1 (TTF-1) immunostains for differentiating poorly differentiated squamous cell carcinoma (PDSCC) from small cell lung carcinoma (SCLC). We used monoclonal antibodies reactive to p63 or TTF-1 to stain 4-μm-thick sections from 30 formalin-fixed, paraffin-embedded lung biopsy and resection specimens and 7 alcohol-fixed, formalin-postfixed, paraffin-embedded cell blocks from lung fine-needle aspirations (FNAs). For p63, we used a streptavidin-biotin kit, diaminobenzidine as the chromogen, and a hematoxylin counterstain. We used automated immunostaining for TTF-1. The 37 cases included 23 SCLCs, 13 PDSCCs, and 1 carcinoma initially diagnosed as PDSCC. All 23 SCLCs were negative or, rarely, equivocal for p63; 20 (87%) of 23 were TTF-1+; nuclear staining ranged from strong and/or frequent to weak and/or uncommon. All 13 PDSCCs were TTF-1–/p63+ with intense staining of 50% to 100% of tumor cells. One case originally diagnosed as PDSCC was TTF-1+/p63–, suggestive of SCLC; after morphologic reexamination and immunostaining for neuroendocrine markers, it was reclassified as intermediate-type SCLC. TTF-1 immunostaining showed equal or increased sensitivity in alcohol-fixed cytologic cell block samples compared with formalin-fixed biopsy material; in 1 SCLC case, the biopsy specimen was TTF-1–; however, the FNA cell block stained positively. p63 and TTF-1 appear to be useful for differentiating SCLC from lung PDSCC in formalin-fixed and alcohol-fixed, formalin-postfixed material.

We studied the usefulness of p63 and thyroid transcription factor-1 (TTF-1) immunostains for differentiating poorly differentiated squamous cell carcinoma (PDSCC) from small cell lung carcinoma (SCLC). We used monoclonal antibodies reactive to p63 or TTF-1 to stain 4-microns-thick sections from 30 formalin-fixed, paraffin-embedded lung biopsy and resection specimens and 7 alcohol-fixed, formalin-postfixed, paraffin-embedded cell blocks from lung fine-needle aspirations (FNAs). For p63, we used a streptavidin-biotin kit, diaminobenzidine as the chromogen, and a hematoxylin counterstain. We used automated immunostaining for TTF-1. The 37 cases included 23 SCLCs, 13 PDSCCs, and 1 carcinoma initially diagnosed as PDSCC. All 23 SCLCs were negative or, rarely, equivocal for p63; 20 (87%) of 23 were TTF-1+; nuclear staining ranged from strong and/or frequent to weak and/or uncommon. All 13 PDSCCs were TTF-1-/p63+ with intense staining of 50% to 100% of tumor cells. One case originally diagnosed as PDSCC was TTF-1+/p63-, suggestive of SCLC; after morphologic reexamination and immunostaining for neuroendocrine markers, it was reclassified as intermediate-type SCLC. TTF-1 immunostaining showed equal or increased sensitivity in alcohol-fixed cytologic cell block samples compared with formalin-fixed biopsy material; in 1 SCLC case, the biopsy specimen was TTF-1-; however, the FNA cell block stained positively. p63 and TTF-1 appear to be useful for differentiating SCLC from lung PDSCC in formalin-fixed and alcohol-fixed, formalin-postfixed material.

Diagnosis of two distinct malignancies in a single sample is rare. Here we report a case of lung adenocarcinoma metastasized to a supraclavicular lymph node which was concomitantly diagnosed with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) using ultrasound-guided fine needle aspiration biopsy (US-FNA) sample.A 62-year-old Caucasian male presented with cough and bloody sputum. US-FNA of a supraclavicular lymph node showed two distinct cell populations and, based on morphological examination and immunohistochemical staining of the FNA cell block slides, diagnosed with CLL/SLL and metastatic lung adenocarcinoma. Flow cytometric analysis of peripheral blood supported the diagnosis of CLL/SLL. To our knowledge, this is a rarely reported cytology case in which metastatic lung adenocarcinoma is concurrently diagnosed with CLL/SLL in a single lymph node and can be diagnosed based an FNA sample.

Early molecular characterization with Kirsten rat sarcoma factor, epidermal growth factor, and anaplastic lymphoma kinase are critical to manage pulmonary adenocarcinoma. Fine-needle aspiration (FNA) of lesions2 cm are routine in our institution and are used in molecular analysis. We report our experience.We searched our databank for primary pulmonary adenocarcinomas diagnosed by FNA between January 2009 and April 2013. Size of the lesion aspirated, molecular results, and sample source (FNA versus surgical specimen) were recorded. We compared the frequency of mutations identified by FNA versus surgical specimens and the frequency of mutations in lesions by size (1 cm, 1-2 cm,2 cm).We identified 397 primary pulmonary adenocarcinomas. Molecular studies were requested by the clinician in 89 (22%) of primary adenocarcinomas. FNAs were used in 55 cases; 51 (93%) yielded sufficient material for molecular studies; surgical tissue were used in 34 cases; 33 (97%) yielded sufficient material for molecular studies. The insufficient specimens came from 2 FNAs of 0.6 cm nodules, an FNA of a 2 cm nodule, and a core biopsy.FNA was adequate for molecular analysis of small nodules. In nodules greater than 0.6 cm, the adequacy is comparable to surgical tissue. There was no statistically significant change in mutation rate by size (53%-58%). Importantly, FNA of small lesions for cytological diagnosis and molecular analysis is encouraged by our data and experience in order to provide early treatment.

Lymphocytic Response and Inducible Nitric Oxide Synthase in WTC-Exposed Chronic Rhinosinusitis Background: A significant number of people exposed to the World Trade Center (WTC) site following the terrorist attacks suffer from sinonasal symptoms. We hypothesize that patients who were acutely exposed but developed chronic symptoms may have a unique lymphocytic profile to sinonasal inflammation. Population: Retrospective review of pathology specimens from WTC-exposed subjects that underwent endoscopic sinus surgery at the Mount Sinai Medical Monitoring and Treatment Programs. Methods: Following approval from the WTC Population Protection Committee and the Mount Sinai Human Subjects Committee, pathology specimen blocks were obtained from 26 WTC-exposed and 26 non-WTC-exposed (control) subjects who underwent sinus surgery. Hematoxilyn & Eosin (H&E) stains were obtained, along with immunohistochemistry (IHC) for inducible nitric oxide synthase (iNOS), CD3, CD4, CD8 and CD20 lymphocytes. Slides were graded by 3 blinded trained raters on a scale of 0 to 3. Results: H&E staining was consistent among all specimens for acute and chronic inflammation. A Mann-Whitney U test was conducted, and the average rank of lymphocyte subpopulations (Controls vs. WTC-exposed) were: CD3 27.23 vs. 23.63 (z = -0.97, p = 0.33), CD4 27.54 vs. 23.29 (z = -1.27, p = 0.20), CD8 25.37 vs. 25.65 (z = -0.07, p = 0.94), CD20 27.15 vs. 23.71 (z = -0.98, p = 0.33), and iNOS 25.20 vs. 24.80 (z = 0.07, p = 0.94). There was no statistically significant difference in grading between the raters (linear-by-linear association, p = 0.18). Discussion: WTC-exposed patients with chronic rhinosinusitis (CRS) have demonstrable disease. Immune response by identification of lymphocytic subpopulation and inflammatory contributions from reactive oxygen species appear comparable to the standard patient with CRS. Clinical Significance: Chronic rhinosinusitis is present in the WTC-exposed population. Although anecdotal experience suggests a unique pattern of disease, the lymphocyte response in this population confirms the need for standardized care.

Syphilis is coming back in the recent a few decades especially in the gay and HIV populations. Since syphilis can be "the great mimic" clinically and pathologically, a case report with updated review can be helpful to the medical community. We report, a case of syphilitic lymphadenitis diagnosed via fine needle aspiration biopsy (FNAB). The pitfalls associated with the diagnosis of syphilitic lymphadenitis will be discussed. The patient's medical records were reviewed. The pertinent history, clinical course, and ancillary studies including FNAB cytology with special stains are presented. In addition to the case report, we discuss the diagnosis of syphilitic lymphadenitis and the role of FNAB cytology. This was a 37-year-old man presenting with a two-month history of a growing neck mass, night sweats, and a ten pound weight loss. The patient had been treated one month earlier for primary syphilis. Examination of the head and neck revealed a 3 cm right level II mass. FNAB cytology showed heterogeneous population of lymphocytes and plasma cells suggesting reactive changes. Modified silver staining of the cell block slide was performed and revealed spirochetes, consistent with syphilis. The patient's lymphadenitis resolved with a course of antibiotic treatment. Although lymphadenopathy is a rare presentation of syphilis, it should be included in the differential diagnosis for patients who offer a suspect history. FNAB with silver staining is an effective, minimally invasive way to confirm the diagnosis.

We report the case of a rare cardiac lesion, mesothelial/monocytic incidental cardiac excrescences, and also provide a review of the literature. Diagnosis of this entity was based on both its unique morphologic features and imunohistochemical stains. Cytokeratin positivity confirmed the epithelial component, mesothelial cells, in the lesion. Positive staining of CD68 in the monocytic-appearing cells revealed the histiocytic nature of the second component of this lesion. Differential diagnoses are discussed. This report emphasizes the diagnostic dilemma encountered with this unusual entity and the possibility of misdiagnosing the epithelial portion as a metastatic lesion or visa versa.

Chronic diseases develop in susceptible individuals following exposure to environmental conditions including high fat diets. Inbred strains of mice differing in susceptibility to atherosclerosis, diabetes, obesity and certain cancers are models for understanding the genetic basis and molecular mechanisms whereby diet influences these polygenic and multifactorial disorders. Expression sequence tags (EST) and disease quantitative trait loci (QTL) are also being identified with these strains. Reported here are comparisons of food intake, growth, nonfasting serum lipids and expression of mRNA for hepatic apolipoprotein E (ApoE), hepatic stearoyl CoA desaturase (Scd1) and heart lipoprotein lipase (Lpl) in a 2 x 2 x 2 design with C57BL/6J and BALB/cByJ mice fed semipurified diets with 4 or 20% saturated (coconut) or unsaturated (corn) oils for 4 mo. Histological studies of aortas and coronary arteries are also reported for these animals. After 4 mo, BALB/cByJ mice were significantly heavier and had significantly higher total serum cholesterol, HDL cholesterol and triglyceride concentrations in the fed state than C57BL/6J mice. Efficiency of utilizing dietary energy did not differ consistently between strains. Oil level affected serum total cholesterol, triglycerides and HDL cholesterol, which were significantly greater in mice fed high fat diets. Lpl and ApoE mRNA expression levels were not significantly affected by mouse strain, oil source or oil level. Scd1 mRNA expression, however, was significantly higher in C57BL/6J than in BALB/cByJ mice and was lower in all mice fed 20% compared with those fed 4% fat diets. Genes regulated differently by diet among strains with distinct susceptibility to diet-influenced disease may be associated with molecular pathways contributing to incidence or severity.

Plasmablastic lymphoma (PBL) is a rare subtype of diffuse large B cell lymphoma and commonly presents as an oral mass in HIV patients. Extraoral PBL has been reported, including one case of primary central nervous system PBL (PCNSPBL). The cytological features of PBL have been described, including cerebrospinal fluid (CSF) cytology findings for secondary CNS involvement by PBL. The etiology of PCNSPBL is still unknown. We report here the CSF cytology of a PCNSPBL, which shows a hypercellular specimen composed of markedly atypical, singly dispersed plasmacytoid cells with frequent abnormal mitoses and binucleation. The neoplastic cells are positive for CD138. Flow cytometry of the CSF specimen demonstrates a monoclonal neoplastic cell population, which is CD138 positive, kappa light chain positive, lambda light chain negative, and CD19 negative. Molecular analysis and immunohistochemical stains on a tissue biopsy confirmed the diagnosis and reveal concurrent infections with Epstein-Barr virus and human polyomavirus JC virus. Clinical and radiological correlations are reported, and the literature is reviewed. To the best of our knowledge, this is the first case report for CSF cytology of a PCNSPBL, demonstrating the utility of the cytological examination in the triage and diagnosis of this disease. Because of its dismal prognosis, it is critical for cytopathologists to be aware of the entity and recognize the neoplastic cells in CSF specimen. This report also emphasizes the importance of clinical and radiological correlation in the diagnosis of this lethal disease.

Fine-needle aspiration (FNA) is a useful tool for immediate assessment of palpable lesions, especially in the head and neck region. The objective of this study is to evaluate the degree of correlation between Diff–Quik-based onsite diagnosis (OD) and final diagnosis (FD) and further improve the efficiency of FNA practice. Two hundred and eighty-seven cytopathologist-performed FNAs from the head and neck region were evaluated. Number of passes, number and type of slides and correlation (agreement, modified final diagnosis and disagreement) between OD and FD were evaluated. Among 287 FNAs, the average number of passes per FNA case was 2 (range, 1–5&.rpar;). The mean number of slides reviewed per case was 5 including 2 Diff–Quik (D–Q)-stained slides, 2 Papanicolaou (Pap)-stained slides, and 1 cell block (CB)/1 cytospin (Cy). 247 of 287 (86%) cases showed agreement between OD and FD. FD on 36 out of 287 cases (12.5%) was slightly modified or refined after reviewing additional slides. A major diagnostic discrepancy was noted in four cases (1.5%), three of which were classified as squamous cell carcinoma on final diagnosis, and confirmed on surgical follow-up. Accurate diagnosis can be achieved in the majority (86%) of head and neck FNAs based on immediate examination of D–Q stained slides alone. In a small number of cases (12.5%), reviewing additional slides may refine the final diagnosis. In rare cases, especially cystic squamous lesions, Pap-stained slides appeared to be helpful. It is plausible to use D–Q-stained slides alone with most head and neck FNAs in order to provide more cost effective and efficient triaging and patient management. Diagn. Cytopathol. 2010;38:846–853. © 2010 Wiley-Liss, Inc..