Immunohistochemistry and immunofluorescence utilization audit by subspecialty in an academic setting: A step toward stewardship.

There are immunohistochemistry (IHC) and immunofluorescence (IF) panels described in the literature and established by personal and institutional experiences that are in common use by pathologists in their daily practice. Stewardship is a difficult discussion because IHC utilization is influenced by many factors including the pathologist's experience, background, practice setting, personal bias, and medicolegal culture. We developed the methodology to audit the IHC/IF utilization in our academic subspecialty practice. We aim to share this methodology and to provide our data that can be used for consideration by other subspecialized academic practices. This analysis included a total of 63,157 specimens that were accessioned during 2022, representing 38,612 cases. The likelihood of ordering IHC/IF ranged from 1 % (in genitourinary pathology) to 59 % (in renal pathology). The average percentage of specimens with IHC/IF was 21 % for the entire practice. In cases where IHC/IF was ordered, the number of stained slides averaged 4.9 per specimen for the entire practice. The number of IHC/IF slides per specimen ranged from 1.9 (in gastrointestinal pathology) to 12.2 (in renal pathology). The highest number of antibodies ordered for a single specimen by subspecialty ranged from 11 (in cardiac pathology) to 63 (in dermatopathology). Renal pathology was the only subspecialty that had an average number of IHC/IF slides that was statistically significantly different from all other subspecialties. We described the various patterns of utilization by subspecialty and rationalized their subtle differences. We also analyzed the types of cases that exceeded the reimbursement limits set by the Centers for Medicare and Medicaid Services (CMS).

Effects of COVID-19 pandemic on cytology: specimen adequacy in fine-needle aspiration of palpable head and neck masses.

INTRODUCTION: At our institution, palpation-guided fine-needle aspiration (FNA) is performed by the cytopathology service on an outpatient basis at the request of otolaryngologist surgeons. The aim of this study is to assess the effect of COVID lockdown measures on our FNA service with specific focus on adequacy rates. MATERIALS AND METHODS: All palpation-guided FNA performed in 2019 to 2020 were identified in our pathology database. Adequacy rates were compared for 3 time periods in 2020: pre-COVID, lockdown, and post-lockdown. RESULTS: In 2019, 121 FNAs were performed with 98% (119 of 121) obtained by pathology and only 2% (2 of 121) obtained by surgeons. In 2020, 89 FNAs were performed with 45% (40 of 89) collected by pathologists and 55% (49 of 89) by surgeons. During the pre-COVID period of 2020, 27 FNAs were collected, 85% (23 of 27) by pathologists, 8.7% of these (2 of 23) were nondiagnostic. Of the 4 FNAs performed by surgeons, all were positive for malignancy. During COVID lockdown all 24 FNAs were performed by surgeons with a 50% (12 of 24) nondiagnostic rate. Post-lockdown, with FNA referrals still below pre-COVID levels, surgeons performed 55.3% (21 of 38) of FNAs with 28.6% (6 of 21) non-diagnostic, while pathology performed 44.7% (17 of 38) with an 11.8% (2 of 17) nondiagnostic rate. CONCLUSIONS: Our FNA service noted significant changes in 2020 as a result of the COVID pandemic. Nondiagnostic rates were significantly increased in 2020 compared with 2019, primarily due to a shift to majority surgeon-performed palpation-guided FNA in the absence of cytopathology service during the lockdown period.

Exploration of INSM1 and hASH1 as additional markers in lung cytology samples of high-grade neuroendocrine carcinoma with indeterminate neuroendocrine differentiation.

BACKGROUND: Traditional neuroendocrine (NE) markers synaptophysin, chromogranin, and CD56 play an integral role in affirming the diagnosis of high-grade lung NE carcinoma, however promising markers, INSM1, and hASH1, have been identified. We investigated the utility of these markers in pulmonary cytology specimens, particularly in cases where results of traditional NE markers were equivocal. METHODS: A retrospective search of cytology cases obtained via endobronchial ultrasound (EBUS)-guided FNA revealed 26 cases of high-grade lung carcinoma where an indeterminate diagnosis of small-cell lung carcinoma (SCLC) was based on equivocal IHC staining with traditional NE markers. A separate cohort of 23 cases positive for all traditional markers with a definitive diagnosis of SCLC was also selected. Cytology cellblock sections were immunostained with INSM1 and hASH1 and analyzed using H-score methodology (score range 0-300). A score of ≥95 was considered "positive." RESULTS: INSM1 was positive in 19/24 (79.2%) of cases of high-grade lung carcinoma with indeterminate NE differentiation, while hASH1 was positive in 6/24 (25.0%). Chromogranin was seen only focally positive (<10% of cells) in 4/24 (16.7%), synaptophysin positive in 16/24 (66.7%), and CD56 positive in 14/21 (66.7%). Among unambiguous cases, INSM1 was positive in all cases with an average score of 233.9, while hASH1 was positive in 21/23 (91.3%) with an average score of 196.3. CONCLUSION: Compared with traditional NE stains and to hASH1, INSM1 was expressed in a higher number of cases of high-grade lung NE carcinomas in cytology cellblock specimens, making it a superior, more sensitive NE marker.

A rare sporadic pancreatic desmoid fibromatosis diagnosed by endoscopic ultrasound-guided fine-needle aspiration: Case report and literature review.

Intra-abdominal desmoid fibromatosis (also known as desmoid tumor) is a rare benign but often locally aggressive infiltrative fibrous proliferation. Pancreatic desmoid fibromatosis is even rarer, with only 31 cases previously reported in the English-language literature. These tumors present a distinct diagnostic challenge due to their rarity and non-specific image findings and presentation, with most cases diagnosed as desmoid fibromatosis only after surgical resection. This report presents a rare case of pancreatic desmoid fibromatosis in a 72 year old man, who on a follow-up CT for a previously diagnosed angiomyolipoma of the kidney was found to have a 4.0 cm pancreatic tail mass. This was sampled pre-operatively by endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA). Examination of the cytology material showed a low-grade spindle cell lesion. Immunohistochemistry (IHC) performed on FNA cell block showed the lesional cells to be positive for beta-catenin, consistent with fibromatosis. Additional mutational analysis on cell block material revealed the characteristic CTNNB1 gene mutation (T41A), confirming the diagnosis. The mass was then surgically resected and again confirmed to be desmoid fibromatosis on histopathologic examination. On review of previously published cases of pancreatic desmoid fibromatosis, most were initially suspected to be some type of pancreatic neoplasm and were not biopsied prior to surgical resection. This case suggests a potential key role for fine-needle aspiration cytology in the preoperative diagnosis of pancreatic and other intra-abdominal desmoid tumors, particularly as evidence emerges that non-surgical treatment may be a viable first option for some cases.

Evaluation and Comparison of Performance Parameters and Impact of Telepathology and Operator Experience on Endobronchial and Endoscopic Ultrasound-Guided Fine-Needle Aspiration.

OBJECTIVES: Endobronchial ultrasound- and endoscopic ultrasound-guided fine-needle aspiration (EBUS-/EUS-FNA) are minimally invasive techniques of diagnosing and staging malignancies. The procedures are difficult to master, requiring specific feedback for optimizing yield. METHODS: Over 2 years, EBUS-/EUS-FNA cases were gathered using the institutional pathology database. Patient and specimen characteristics were collected from the pathology database and electronic medical record. RESULTS: In 2 years, 789 unique FNA specimens were collected (356 EBUS and 433 EUS specimens). The cohort and each subgroup had excellent performance, which was enhanced by telepathology. The discrepancy rate was satisfactorily low. Hematolymphoid neoplasms are overrepresented in discrepant EBUS cases. The malignancy rates of cytology diagnostic categories were comparable to the literature. CONCLUSIONS: Using diagnostic yield and concordance results allow for comprehensive evaluation of the entire process of EBUS-/EUS-FNAs. This study's findings can influence patient management, training methods, and interpretation of results, while also acting as a model for others to investigate their own sources of inadequacy, discrepancy, and training gaps.

Performance of Ventana SP263 PD-L1 assay in endobronchial ultrasound guided-fine-needle aspiration derived non-small-cell lung carcinoma samples.

BACKGROUND: Introduction of programmed death-ligand 1 (PD-L1) inhibitors has significantly changed the treatment landscape of non-small-cell lung carcinomas (NSCLC). Since endobronchial ultrasound guided fine-needle aspiration (EBUS FNA) has become the primary diagnostic and staging modality for NSCLC, this study was pursued to determine the adequacy of Ventana SP263 PD-L1 assay in cytology cell blocks. DESIGN: Fifty NSCLC cases with cytology and corresponding histology specimens obtained between 2014 and 2018 were identified. After assessing for adequacy (100 or more tumor cells), forty cases were selected for Ventana SP263 PD-L1 immunohistochemistry (IHC) assay and assessed for tumor proportion scores (TPS) and staining intensity scores (SIS) and analyzed for concordance. RESULTS: Of the 40 matched pairs 33 (82.5%) showed concordant PD-L1 expression. On cytology, 32 cases were positive (8 high-expressors and 24 low-expressors) of which 27 were concordant and 5 discordant with matched histology specimens. On histology, 29 cases were positive (7 high-expressor and 22 low-expressors) while 11 cases were negative for PD-L1 expression of which 6 had concordant negative cytology. The intraclass correlation coefficients (ICC) for TPS was 0.81 with 95% confidence interval (0.68, 0.9) and for the SIS, it was 0.78 with 95% CI (0.62, 0.88), both considered as having excellent agreement. CONCLUSION: With an overall concordance rate of 82.5% between cytology and histology specimen, this study demonstrates the feasibility of PD-L1 IHC with SP263 clone on cytology samples of NSCLC and adds to a growing body of evidence validating the use of cytology cell blocks for PD-L1 expression testing.

Oncocytic features in salivary duct carcinoma, a potential pitfall for misdiagnosis as Warthin tumor in fine needle aspiration specimens: A cytomorphologic analysis of 14 cases.

BACKGROUND: Salivary duct carcinoma (SDC) is an uncommon and highly aggressive primary salivary gland neoplasm. Cytomorphologic features of SDC include cellular smears, nuclear atypia, prominent nucleoli, cribriform and papillary architecture, and background necrosis. The presence of oncocytic features has been described but not adequately characterized in the current literature. METHOD: This study cohort consisted of 14 cases of histologically proven SDC with previous salivary gland fine needle aspiration (FNA). The cytologic material of each case was semi-quantitatively analyzed and evaluated for various cytomorphologic, architectural, and background features. RESULTS: Twelve SDCs were located in the parotid gland and two in the submandibular gland. In two cases the initial cytologic diagnoses was Warthin tumor or favor Warthin tumor. Moderate to marked degree of oncocytic changes were noted in all cases except one case. Nuclear atypia was variable with most cases exhibiting moderate to high-grade nuclear features, while four cases demonstrated low-grade nuclear cytomorphology. Cytoplasmic vacuolation was seen in nine cases and variable amount of background necrosis was observed in eight cases. Cribriform and papillary architecture was recognized in only six cases. Background lymphocytes were absent in all but one case. CONCLUSIONS: Precise diagnosis of SDC based on cytomorphologic features alone can be challenging. Oncocytic change is one of the most consistent features observed in this case series and when associated with less pronounced cytologic atypia, can potentially lead to misdiagnosis as Warthin tumor. SDC should be considered in the differential diagnosis of oncocytic salivary gland neoplasms where precise diagnosis is not possible.

Cytomorphologic features of malignant solitary fibrous tumor with mediastinal involvement sampled by endoscopic and endobronchial ultrasound-guided fine-needle aspiration: A comparison of two cases.

Solitary fibrous tumor (SFT) is an uncommon fibroblastic neoplasm with considerable risk of local recurrence. SFT is histologically characterized by bland spindled-to-epithelioid cells in alternating hyper- and hypocellular zones, a "patternless pattern," ectatic "staghorn" vessels with variable edematous perivascular stroma, and thick ropey collagen. Cytologically, smears are variably cellular with spindled-to-epithelioid cells with oval nuclei, wispy cytoplasm, multiple inconspicuous nucleoli, and occasional nuclear pseudoinclusions. Small vessels and bare/stripped nuclei are generally present while mild atypia is not uncommon. STAT6 nuclear expression is the most useful immunohistochemical stain and is the product of a NAB2-STAT6 gene fusion. SFTs with mediastinal involvement may be diagnostically challenging due to proximity to vital structures and anticipated patient risks. Endobronchial and endoscopic ultrasound-guided fine-needle aspiration (EBUS/EUS-FNA) are minimally-invasive tissue sampling methods that provide diagnostic material while minimizing patient risk, and the mediastinum is accessible by both procedures. Small aspirate samples and SFT nonspecific features can compound the diagnostic difficulty, although familiarity with the cytologic, morphologic, immunophenotypic, and genetic features of SFTs assist the pathologist in confirming the diagnosis. Pathologists must also be aware of high-risk SFT features to ensure appropriate therapy and management. Case #1 describes a recurrent mediastinal SFT with high-risk features sampled by EUS-FNA. Case #2 describes a primary diagnosis of mediastinal SFT with malignant behavior made on an EBUS-FNA specimen.

Efficacy of endoscopic-guided fine-needle aspiration in the diagnosis of gastrointestinal spindle cell tumors.

BACKGROUND: Spindle cell neoplasms of the gastrointestinal (GI) tract constitute a wide group of lesions that may raise diagnostic difficulties on hematoxylin-eosin-stained slides. Appropriate endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) technique with sufficient cell block material for immunohistochemistry (IHC) can lead to accurate diagnosis. METHODS: This is a retrospective study of 29 cases obtained from our institution's records over a five-year period (2011-2015). Cytomorphology, histology (when available), IHC, FNA procedure details, imaging characteristics, and clinical history were reviewed. Rapid onsite evaluation (ROSE) was used in all cases. Cytologic samples were correlated with surgical pathology resection specimens when available. RESULTS: Eighteen GI stromal tumors, six leiomyomas, two schwannomas, and one granular cell tumor were analyzed; two cases were not amenable for a definitive diagnosis: one showed fragments of smooth muscle not otherwise specified (smooth muscle vs. leiomyoma) and the other one was insufficient for diagnosis. Locations included stomach, esophagus, duodenum, and colon. EUS-FNA was performed with different gauge needles. Total number of passes ranged between two and nine. We found no evidence that larger-sized needles are superior in procuring adequate lesional tissue. Cell block material was stained with various antibodies. Fourteen surgical resection specimens available showed 100% correlation between cytology and histology. None of the neoplasms recurred until now; one patient succumbed to known esophageal squamous cell carcinoma. CONCLUSION: FNA is a pivotal and inexpensive method for rapid evaluation of GI spindle cell tumors and should be used widely in the attempt to avoid unnecessary surgery. Size of needle used for EUS-FNA does not seem to influence the yield of lesional tissue; rather, ROSE can guide the number of passes and subsequently lead to an adequate cell block.

Metastatic medullary thyroid carcinoma or calcitonin-secreting carcinoid tumor of lung? A diagnostic dilemma in a patient with lung mass and thyroid nodule.

Calcitonin-secreting neuroendocrine tumors are rare and have been reported in literature as case reports or case series in various organs including lung, pancreas, larynx, bladder, and ovary. These tumors have similar cytologic features and immunohistochemical profile to medullary thyroid carcinoma and thus it is difficult to distinguish them, especially when calcitonin-secreting neuroendocrine tumors are intermediate or higher grade and there is a mass lesion in the thyroid gland. Here, we report a rare case of calcitonin secreting atypical carcinoid tumor of the lung in a patient with thyroid nodule. However, after extensive ancillary studies on the thyroid gland, no tumor was detected and subsequent resection specimen revealed a pulmonary atypical carcinoid tumor with metastasis to level 11 lymph node. Being aware of this entity has significant clinical, diagnostic, and therapeutic implications and can prevent unnecessary thyroidectomies with subsequent possible morbidities.

Laryngeal chondrosarcoma mimicking medullary thyroid carcinoma on fine-needle aspiration cytology: A case report of a diagnostic pitfall.

Chondrosarcoma (CS) of larynx is a rare laryngeal tumor accounting about 1% of laryngeal malignancies. When CS arises from thyroid cartilage, it may clinically present as a thyroid nodule. Here we report a rare case of CS of thyroid cartilage misinterpreted as medullary thyroid carcinoma. The main aim of this case report is to emphasize the important role of accurate clinical history, appropriate physical examination, and proper localization of the tumor and clear definitive imaging in conjunction with interpretation of cytologic smears. When any of these roles are unclear, it may result in misinterpretation of the cytologic smears. In these unusual circumstances, when cytomorphologic features does not completely fit an entity, communication with the physician and the consideration of a broad differential diagnoses in the head and neck pathology may lead to correct diagnosis and avoid diagnostic pitfalls. Also in certain conditions, ancillary studies including laboratory tests are necessary for definitive classification.

Pancreatic involvement by metastasizing neoplasms as determined by endoscopic ultrasound-guided fine needle aspiration: A clinicopathologic characterization.

BACKGROUND: Pancreatic tumors often represent primary neoplasms, however organ involvement with metastatic disease can occur. The use of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) to determine the underlying pathology provides guidance of clinical management. METHODS: 25 cases were identified in a retrospective review of our institution's records from 2006 to 2016. Clinical parameters and prognosis are described. RESULTS: Metastatic lesions to the pancreas diagnosed by EUS-FNA accounted for 4.2% of all pancreatic neoplastic diagnoses, each lesion had a median greatest dimension of 1.5 cm, were most often located in the head of the pancreas, and by EUS were typically hypoechoic masses with variably defined borders. Patients were of a median age of 64 years old at diagnosis of the metastatic lesion(s) and the mean interval from primary diagnosis to the diagnosis of metastasis to the pancreas was 58.7 months (95% confidence interval, CI, 35.4 to 82.0 months). The rates of 24-month overall survival after diagnoses of metastatic renal cell carcinoma or all other neoplasms to the pancreas were 90% and 7% respectively. The origin of the neoplasms included the kidney (n = 10), colon (n = 4), ovary (n = 3), lung (n = 2), et al. Smear-based cytomorphology, and a combination of histomorphology and immunohistochemical studies from cell block preparations showed features consistent with the neoplasm of derivation. CONCLUSION: Metastases to the pancreas can be diagnosed via EUS-FNA, with enough specimen to conduct immunohistochemical studies if necessary to delineate origin. The determination of metastatic disease to the pancreas alters management and prognosis of the patient. Diagn. Cytopathol. 2017;45:418-425. © 2017 Wiley Periodicals, Inc.

Undifferentiated (anaplastic) carcinoma with osteoclast-like giant cells of the pancreas: a series of 5 cases with clinicopathologic correlation and cytomorphologic characterization.

INTRODUCTION: Undifferentiated carcinoma with osteoclast-like giant cells of the pancreas (UCOGCP) is a rare neoplasm involving the pancreas. Although typically diagnosed initially via endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), cytomorphologic characterization of the neoplasm has been limited to individual cases in the literature. MATERIALS AND METHODS: Five cases were identified in a retrospective review of our institution's records from 2006 to 2015. Cytomorphologic, immunophenotypic, and corresponding clinical features of the neoplasm are examined and described. RESULTS: UCOGCP accounted for 0.9% of all new pancreatic neoplastic diagnoses, had a median greatest dimension of 4.3 cm, were variably located within the pancreas, and had variable features by radiologic imaging. Patients were of a median age of 78 years old at diagnosis, and had a median length of survival of 10 months. Smear-based cytomorphology and histomorphology from cell block preparations show atypical/pleomorphic mononuclear carcinomatous and bland osteoclast-like giant cellular populations. The immunophenotype of the mononuclear carcinomatous component was CD68, CD99, CK7 (variably), CKAE1/AE3 (variably), and, rarely, p40-positive. The osteoclast-like giant cells positively expressed CD68 and CD99. CONCLUSIONS: Initial diagnosis of UCOGCP is frequently made via EUS-FNA of pancreas tumors, with cytomorphologic features on smears and hematoxylin and eosin stained slides prepared from cell block material being characteristic for the diagnosis. Although the cellular constituents have a consistent immunophenotype, the diagnosis can be based on the morphologic features alone. UCOGCP is an important diagnosis as it may have a distinct clinical course from undifferentiated carcinomas of the pancreas lacking osteoclast-like giant cells.

Internal validation testing for new technologies: bringing telecytopathology into the mainstream.

Implementing new technology in the laboratory can improve processes and patient care, but compliance with regulatory requirements can be a significant hurdle to clear. This study provides a detailed procedure to address user training, competency assessment, and internal validation of telecytopathology simultaneously, while fulfilling regulatory requirements set forth by the College of American Pathologists and CLIA '88. Six pathologists participated in this study. Methods and materials used included a blind correlation study between diagnoses rendered via telecytopathology and via direct microscopy on 10 finalized fine needle aspiration (FNA) cases. The first step of this procedure involved each pathologist to render a diagnosis for each specimen using telecytopathology. The second step was to allow each pathologist to diagnose each specimen via direct microscopic review after a wait period of at least 6 weeks. The diagnoses rendered via telecytopathology were then compared to both the established final diagnoses and the secondary direct microscopic review diagnoses to examine interpathologist and intrapathologist reproducibility with a passing rate of 90% or better. Results of the study yielded an average concordance rate of 96.67% for interpathologist reproducibility and 95% for intrapathologist reproducibility across all participating pathologists. All participants passed the assessment with a rate of 90% or better, proving evidence of competency. This study confirmed user competency and validated telecytopathology as an effective tool for examining and diagnosing cytology FNA specimens remotely. It also satisfied regulatory compliance requirements to ensure high quality of diagnostic testing and patient care.

Focus on technology: How important is resolution in telecytopathology?

BACKGROUND: The authors conducted an analysis of 2 telepathology systems with different resolutions to determine how resolution affects the pathologists' ability to provide preliminary diagnoses for fine-needle aspirations (FNA). METHODS: FNA cases evaluated by telepathology between February 1, 2011 and January 18, 2012 were reviewed. Concordance indices between preliminary and final diagnoses were calculated for cases assessed with two proprietary systems (the Remote Meeting Technologies iMedHD system and the Olympus NetCam system) using 3 diagnostic classifications (negative, atypical, and suspicious/positive). A Wilcoxon rank-sum test was used to compare the number of passes necessary to determine adequacy. RESULTS: In total, 298 NetCam cases and 26 iMedHD cases were evaluated. The concordance index, which was calculated using the 3 classifications, was 0.943 (95% confidence interval, 0.922-0.963) for NetCam compared with 0.951 (95% confidence interval, 0.898-1.000) for iMedHD. The mean value for the number of passes required to determine adequacy was 2.2 for NetCam and 2.1 for iMedHD (P = .838). CONCLUSIONS: The results from statistical analyses demonstrated no difference in the concordance indices between preliminary and final diagnoses or in the number of passes necessary to render adequacy between the 2 telepathology systems. However, because it had higher resolution along with other features, the iMedHD system achieved greater user satisfaction.

Significance of atypical category in voided urine specimens prepared by liquid-based technology: Experience of a single institution.

INTRODUCTION: The goal of this study was to evaluate the clinical significance of atypical cytology in voided urine samples. We also studied any differences in outcome that may exist between the patients being surveyed versus high risk for urothelial carcinoma (UC). MATERIALS AND METHODS: This was a retrospective study of all voided urine specimens with "atypical" cytology over a 10-year period. The patients were categorized into those with and without a prior diagnosis of UC as the "surveillance" and "de novo" (DG) groups. Follow-up was obtained. Clinical impact and outcomes of the 2 groups were compared. RESULTS: In this study, 5.7% of voided urine specimens were atypical. Mean age of patients in years, male/female ratio, and time to diagnosis in days was 59 versus 71, 23:15 versus 22:1, and 95 versus 43 in the DG and surveillance group, respectively. Rate of progression to UC was similar in both groups. High-grade UC was significantly higher in the DG. CONCLUSIONS: Approximately 20% of patients in the DG were subsequently diagnosed with UC. The common causes for the atypical diagnosis that did not progress to UC were stones and benign prostatic hyperplasia. In the absence of an etiology for the atypia, further investigations are warranted.

Cytopathologic diagnosis of esophageal glomus tumor presenting as an incidental posterior mediastinal mass in an 80-year-old male.

Endoscopic ultrasound guided fine-needle aspiration (FNA) of the upper gastrointestinal tract presents a diagnostic challenge to cytopathologists due to the broad differential diagnosis and morphologic overlap between various entities in this location. We report here an incidentally discovered case of esophageal glomus tumor presenting as a posterior mediastinal mass in an 80-year old male. Glomus tumor is a rare soft tissue neoplasm with bland epithelioid morphology and cytoplasmic granularity. Literature review reveals only 6 published cases of esophageal glomus tumor in the general pathology literature. To our knowledge, this is the first report in the English literature to describe FNA cytology of an esophageal glomus tumor. This rare case presentation provides the opportunity to review the differential diagnosis for lesions of the upper gastrointestinal tract and their appearance on FNA in order to clarify an entity that is uncommon in everyday cytology practice.

Kaposi sarcoma herpesvirus/human herpesvirus-8-negative effusion-based lymphoma: report of 3 cases and review of the literature.

BACKGROUND: Primary effusion lymphoma (PEL) is a rare subtype of large B-cell lymphoma that arises in body cavities without detectable tumor masses. PEL is universally associated with Kaposi sarcoma herpesvirus (KSHV)/human herpesvirus-8 (HHV8). Despite overlapping features, KSHV/HHV8-negative effusion-based lymphoma is a distinct entity from PEL. To date, 52 cases have been reported. The authors report 3 additional cases received in their laboratory from 2007 to 2012. METHODS: Clinical data, cytomorphologic features, and immunophenotypic features of the 3 cases were described and compared with those reported in the literature. RESULTS: The cells in HHV8-negative effusion lymphoma commonly revealed large cell, immunoblastic morphology and B-cell immunophenotype. The 3 cases demonstrated cytomorphologic and immunophenotypic variability. Cytomorphologically, 1 case contained large, highly atypical cells with a moderate amount of cytoplasm, round nucleus, coarsely granular chromatin, and a single macronucleolus. The other 2 cases had medium to large atypical cells with high nuclear-to-cytoplasmic ratios, slightly irregular to cleaved nuclei, and multiple conspicuous nucleoli. One case had a null phenotype with aberrant cytokeratin expression. B-cell phenotype was established by clonal immunoglobulin heavy-chain rearrangement using polymerase chain reaction, whereas the other 2 cases demonstrated a B-cell phenotype by flow cytometry and immunohistochemical staining. All 3 cases were negative for both HHV8 and Epstein-Barr virus. CONCLUSIONS: HHV8-negative effusion lymphoma exhibits clinical, cytomorphologic, and immunophenotypic variability. Cases with a null-phenotype can be particularly challenging. When effusion lymphoma is suspected, ancillary tests are helpful. Moreover, HHV8 detection is critical in differentiating PEL and HHV8-negative effusion lymphoma, because they have overlapping features yet different prognoses.

Swine models of cystic fibrosis reveal male reproductive tract phenotype at birth.

Nearly all male cystic fibrosis (CF) patients exhibit tissue abnormalities in the reproductive tract, a condition that renders them azoospermic and infertile. Two swine CF models have been reported recently that include respiratory and digestive manifestations that are comparable to human CF. The goal of this study was to determine the phenotypic changes that may be present in the vas deferens of these swine CF models. Tracts from CFTR(-/-) and CFTR(ΔF508/ΔF508) neonates revealed partial or total vas deferens and/or epididymis atresia at birth, while wild-type littermates were normal. Histopathological analysis revealed a range of tissue abnormalities and disruptions in tubular organization. Vas deferens epithelial cells were isolated and electrophysiological results support that CFTR(-/-) monolayers can exhibit Na(+) reabsorption but reveal no anion secretion following exposure to cAMP-generating compounds, suggesting that CFTR-dependent Cl(-) and/or HCO(3)(-) transport is completely impaired. SLC26A3 and SLC26A6 immunoreactivities were detected in all experimental groups, indicating that these two chloride-bicarbonate exchangers were present, but were either unable to function or their activity is electroneutral. In addition, no signs of increased mucus synthesis and/or secretion were present in the male excurrent ducts of these CF models. Results demonstrate a causal link between CFTR mutations and duct abnormalities that are manifested at birth.