Search

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.)

BACKGROUND Anaplastic thyroid carcinomas are aggressive malignancies associated with poor clinical outcomes and challenges in diagnosis. While local/regional disease in the neck is the most usual site of biopsy, in some cases, distant metastases may be the site of initial investigation. CASE REPORT A 66-year-old woman with a clinical concern for diffuse metastatic malignancy of unknown primary presented to the Emergency Department (ED) with jaundice and shortness of breath. Recent laboratory test results revealed an elevated CA 19-9. Urinalysis revealed hematuria, proteinuria, and hyperbilirubinemia. She had a computed tomography (CT) scan of the chest, abdomen, and pelvis revealing diffuse involvement of the liver, lungs, adrenals, kidneys, thyroid, pancreas, gallbladder, and brain, but had not yet had a biopsy for definitive diagnosis. An ultrasound-guided liver biopsy was evaluated for cytological features, histological features, and pattern of immunostaining. The cytomorphological histological features were concerning for a high-grade malignancy. Immunohistochemical evaluation revealed that the lesion was positive for CK-AE1/AE3, BRAF, CK7, GATA3, SATB2, PAX8, and TTF-1, but the lesion was not reactive to the following stains: napsin, CK20, CDX2, PCEA, calcitonin, ER and thyroglobulin. The patient was diagnosed with a sarcomatoid anaplastic thyroid carcinoma and died within a few days after diagnosis. CONCLUSIONS This case illustrates that unanticipated specific diagnoses of widely metastatic anaplastic thyroid carcinoma are feasible when integration of patient history, clinical setting, imaging findings, clinical laboratory results, cytomorphology, histomorphology, and results of ancillary immunohistochemical testing are thoughtfully pursued and synthesized.

Background: Obtaining a diagnosis and treating pulmonary malignancies during the same anesthesia requires either an on-site pathologist or a system for remotely evaluating microscopic images. Cytology specimens are challenging to remotely assess given the need to navigate through dispersed and three-dimensional cell clusters. Remote navigation is possible using robotic telepathology, but data are limited on the ease of use of current systems, particularly for pulmonary cytology., Methods: Air dried modified Wright-Giemsa stained slides from 26 touch preparations of transbronchial biopsies and 27 smears of endobronchial ultrasound guided fine needle aspirations were scored for ease of adequacy assessment and ease of diagnosis on robotic (rmtConnect Microscope) and non-robotic telecytology platforms. Diagnostic classifications were compared between glass slides and the robotic and non-robotic telecytology assessments., Results: Compared to non-robotic telecytology, robotic telecytology had a greater ease of adequacy assessment and non-inferior ease of diagnosis. The median time to diagnosis using robotic telecytology was 85 s (range 28-190 s). Diagnostic categories were concordant for 76% of cases in robotic versus non-robotic telecytology and 78% of cases in robotic telecytology versus glass slide diagnosis. Weighted Cohen's kappa scores for agreement in these comparisons were 0.84 and 0.72, respectively., Conclusions: Use of a remote-controlled robotic microscope improved the ease of adequacy assessment compared to non-robotic telecytology and enabled strongly concordant diagnoses to be expediently rendered. This study provides evidence that modern robotic telecytology is a feasible and user-friendly method of remotely and potentially intraoperatively rendering adequacy assessments and diagnoses on bronchoscopic cytology specimens., (© 2023 Wiley Periodicals LLC.)

Background: Endobronchial ultrasound-guided transbronchial fine needle aspiration (EBUS-FNA) has revolutionized the diagnostic and staging approach to non-small cell carcinoma and thoracic lymphadenopathy. However, obstacles to efficacy of rapid on-site evaluation (ROSE) of the samples include variability in sample quality and slow and cumbersome process in the procedure room leading to extended procedure time. The purpose of this pilot study was to evaluate the feasibility and specimen quality of lymph node biopsies prepared through a novel automated system for automated fixation, drying and staining compared to standard slide preparation method., Methods: We performed a prospective, single-center pilot feasibility study of patients undergoing EBUS. Samples were split into conventional standard of care (SOC) slide preparation and preparation using the device ("instrument"). Pathologists compared the SOC slides to the slides prepared by the automated system and assessed the following metrics: nuclear and cytoplasmic quality, presence of debris/artifact, staining quality, creation of a monolayer, and ease of adequacy/diagnosis assessment. A score between 1 (lowest quality) and 3 (highest quality) was assigned to the above metrics., Results: Sixty patients were recruited. One to three lymph nodes were sampled for each patient for a total of 72 samples collected. The mean scores of each assessment category showed no statistical difference between the two preparation techniques except for improved monolayer creation in the instrument samples. Thirty of thirty-one (96.8%) paired samples in the final analysis showed diagnostic equivalency between the automated slides and conventional slides; the discordant pairing was reported to be suspicious on the instrument sample and atypical on the SOC., Conclusions: Study results suggest that slides prepared by the automated system are of adequate quality for adequacy assessment with diagnostic concordance when compared to SOC slides., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-81/coif). AB is an employee of ASP Health. HS is the co-founder and shareholder of ASP Health. JR received an internal grant and equipment loan for this study from ASP Health. The grant was an intramural career development award given to JR to further her research in bronchoscopy. The grant covers internal costs associated with publication fees, statistical costs, and IRB-related costs to facilitate career development for physician scientist investigators. The other authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Aims: Due to its rarity and non-specific clinical and pathological features, low-grade adenosquamous carcinoma (LGASC) of the breast continues to pose diagnostic challenges. Unlike other triple-negative breast carcinomas, LGASC tends to have an indolent clinical behaviour. It is essential to recognise this lesion for accurate diagnosis and appropriate management., Methods and Results: Twenty-five cases of LGASC were identified in our archives and collaborating institutes. Cases of LGASC with dominant coexisting other type carcinomas were excluded. We studied the clinical presentation, morphological features, patterns of the commonly used immunohistochemical stains and follow-up. In our cohort, LGASC was commonly located at the outer aspect of the breast and associated with intraductal papilloma. The morphology of LGASC is characterised by infiltrating small glands and nests with variable squamous differentiation. We also found cuffing desmoplastic (fibrolamellar) stromal change in 75% of patients and peripheral lymphocytic aggregates in 87.5% of patients. P63 and smooth muscle myosin (SMM) were the most common myoepithelial markers used to assist in diagnosis. P63 often stained peripheral tumour cells surrounding invasive glands (circumferential staining in 80% of the cases), mimicking myoepithelial cells. It also stained the small nests with squamous differentiation. However, SMM was negative in 63% of the cases. The vast majority of our cases were triple-negative; only a few had focal and weak expressions of ER and PR. One patient who did not have excision developed lymph node metastasis. Most patients underwent excision or mastectomy with negative margins as surgical treatment; there were no recurrences or metastases in these patients with clinical follow-ups up to 108 months., Conclusions: LGASC has some unique, although not entirely specific, morphological features and immunohistochemical staining patterns. Fibrolamellar stromal change, peripheral lymphocytic aggregates and variable staining of p63 and SMM are valuable features to facilitate the diagnosis., (© 2023 The Authors. Histopathology published by John Wiley & Sons Ltd.)

Introduction: In evaluating malignant pleural fluid cytology, metastatic adenocarcinomas and mesotheliomas are often differential diagnoses. GATA binding protein 3 (GATA3) has historically been used to confirm metastatic breast carcinomas; however, GATA3 has low specificity if mesothelioma is included in differential diagnoses. Trichorhinophalangeal syndrome type 1 (TRPS1) protein is expressed in all types of breast carcinomas, with reported high specificity and sensitivity. We investigated the performance of TRPS1 immunohistochemistry (IHC) and compared it to GATA3 in pleural fluids diagnosed with metastatic breast carcinoma and mesothelioma., Methods: Thirty-six consecutive ThinPrep pleural fluids and 4 pleural fine needle aspirations (FNAs) with diagnoses of metastatic breast carcinoma (21) and mesothelioma (19) were retrieved, and IHC with TRPS1 and GATA3 was performed on all. Immunoreactivity scores for TRPS1 were calculated by multiplying percentage of immunoreactive cells by staining intensity. Immunoreactivity scores were negative if 0 or 1, low positive if 2, intermediate positive if 3 or 4, or high positive if 6 or 9. Nuclear immunoreactivity of ≥10% with at least moderate intensity was judged GATA3 positive., Results: GATA3 showed immunoreactivity in all metastatic breast carcinomas and 84% of mesotheliomas. TRPS1 was immunoreactive in all breast carcinoma cases (18 with a score of 9 and 3 with a score of 6). TRPS1 showed low positivity in 5% of mesothelioma cases with all other cases being negative., Conclusion: When cytomorphologic differential diagnoses of mesothelioma exist, TRPS1 is a more specific marker than GATA3 for confirmation of metastatic breast carcinoma in pleural fluid cytology., (© 2023 Wiley Periodicals LLC.)

Lymphangioleiomyomatosis (LAM) is a rare disease with variable presentations. The neoplastic cells in LAM demonstrate a unique and diagnostically important "myomelanocytic" phenotype. Cytologic reports of LAM are infrequent and have not in the past emphasized the floating island pattern in which circumscribed aggregates of lesional cells are rimmed by appliques of flattened endothelium. This case illustrates the cytology of LAM and emphasizes that the floating island cytoarchitectural pattern more classically associated with entities such as hepatocellular carcinomas may be seen in cytological preparations of LAM at unanticipated body sites., (© 2023 Wiley Periodicals LLC.)

Malignant rhabdoid tumor of the kidney (MRTK) is a rare aggressive pediatric renal tumor which can be diagnosed via fine-needle aspiration (FNA) cytology and core biopsy. The diagnosis of MRTK is challenging, and requires morphologic, immunohistochemical and clinical correlation to distinguish it from other entities. The differential diagnosis includes Wilms tumor, desmoplastic small round cell tumor, rhabdomyosarcoma, synovial sarcoma, renal medullary carcinoma, and epithelioid sarcoma. Here we describe a case of MRTK diagnosed on renal cytology and core biopsy with immunohistochemistry and follow by nephrectomy with gross and morphologic findings., Competing Interests: Declaration of competing interest None. No grants or external sources of funding are pertinent to this report., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Crystal-storing histiocytosis (CSH) is a rare disorder characterized by the accumulation of crystalized immunoglobulins within the cytoplasm of histiocytes. It is often associated with an underlying lymphoproliferative or plasma cell disorder. Most patients with CSH are asymptomatic in regard to the disease and are incidentally discovered. Herein we present cyto-histologic correlation of a rare example of CSH presenting with a two-year interval between original diagnosis of CSH and confirmation of a low-grade B-cell lymphoma., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Biphasic squamoid alveolar renal cell carcinoma is a newly described rare morphologic variant of papillary renal cell carcinoma. Its characteristic histomorphology and immunophenotype have been well described in the literature. Namely, BSARCC is composed of a dual-cell population with nests of larger squamoid cells surrounded by a single layer of cuboidal cells in alveolar arrangements. Invariably, the squamoid component expresses cyclin D1. More recently, MET alterations have been identified within a subset of BSARCC, raising the possibility for targeted MET inhibitor therapy. To the best of our knowledge the cytomorphologic features of BSARCC have yet to be described. Herein we correlate the cytologic features (percutaneous image-guided fine needle aspiration) of BSARCC to its corresponding histomorphology and immunophenotype (core needle biopsy)., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Mammary Analogue Secretory Carcinoma (MASC) is a recently described salivary gland tumor frequently sampled via fine-needle aspiration. The cytologic features of MASC are not entirely distinctive and can simulate acinic cell carcinoma, but the tumor harbors an ETV6 gene rearrangement resulting in an ETV6-NTRK3 fusion gene. We present a case of MASC arising in a 31 year old man with a history of multiple radio-embolization procedures., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Malignant gastrointestinal neuroectodermal tumor (GNET) is a rare malignant primary gastrointestinal mesenchymal tumor which can be diagnosed via fine-needle aspiration (FNA) cytology. In the context of FNA, the diagnosis requires a cell block and the use of significant resources including immunohistochemical stains and molecular testing. The differential diagnosis of GNET includes clear cell sarcoma (CCS), gastrointestinal stromal tumor (GIST), gastric schwannoma, metastatic melanoma, malignant perivascular epithelioid cell tumor (PEComa) and granular cell tumor, among others. Here we describe a case which was initially diagnosed as malignant granular cell tumor by FNA which was later revised to GNET following the finding of an EWSR1-ATF1 fusion gene rearrangement., (Copyright © 2021. Published by Elsevier Inc.)

A 34-year-old male presented with a swelling on the volar surface of the third digit of his right hand. This swelling was associated with pain and erythema. Ultrasound-guided needle biopsy was performed. Cytologic and histologic preparations together confirmed the diagnosis of a rarely encountered mixed epithelial and mesenchymal proliferation, an eccrine angiomatous hamartoma. To our knowledge, this case is the first to illustrate the cytomorphologic features of this rare lesion., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The rapidly spreading COVID-19 pandemic demanded immediate organizational pivots in departments of laboratory medicine and pathology, including development and implementation of severe acute respiratory syndrome coronavirus 2 diagnostics in the face of unprecedented supply chain shortages. Laboratory medicine and pathology educational programs were affected in numerous ways. Here, we overview the effects of COVID-19 on the large, academic Department of Laboratory Medicine and Pathology educational practice at Mayo Clinic, highlighting lessons learned for the post-pandemic era and planning for the possibility of a future pandemic., Competing Interests: Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Patel reports grants from Merck, ContraFect, TenNor Therapeutics Limited and Shionogi. Dr Patel is a consultant to Curetis, Specific Technologies, Next Gen Diagnostics, PathoQuest, Selux Diagnostics, 1928 Diagnostics, PhAST, and Qvella; monies are paid to Mayo Clinic. Dr Patel is also a consultant to Netflix. In addition, Dr Patel has a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an anti-biofilm substance issued. Dr Patel receives an editor’s stipend from IDSA and honoraria from the NBME, Up-to-Date and the Infectious Diseases Board Review Course., (© The Author(s) 2021.)

Rosai-Dorfman disease is a rare proliferative histiocytic disorder of lymph nodes that is descriptively known as sinus histiocytosis with massive lymphadenopathy. Extranodal involvement of the parenchyma of the breast is uncommonly reported, with fewer than 50 cases of mammary extranodal disease detailed in the English-language literature. We characterize a retrospective series of adult female patients from a single institution with Rosai-Dorfman disease of the breast and axillary lymph nodes. Because Rosai-Dorfman disease of the breast and axillary lymph nodes may clinically, radiographically, and histologically mimic breast carcinoma and other conditions, we present an illustrated review of the disease and its relevant differential diagnoses in hopes of raising awareness and allowing for accurate management of affected patients.

Context.—: The Paris System for Reporting Urinary Cytology has been disseminated since its inception in 2013; however, the daily practice patterns of urinary tract cytopathology are not well known., Objective.—: To assess urinary tract cytopathology practice patterns across a variety of pathology laboratories to aid in the implementation and future update of the Paris System for Reporting Urinary Cytology., Design.—: A questionnaire was designed to gather information about urinary tract cytopathology practices and mailed in July 2014 to 2116 laboratories participating in the College of American Pathologists interlaboratory comparison program. The participating laboratories' answers were summarized., Results.—: Of the 879 of 2116 laboratories (41%) that participated, 745 (84.8%) reported processing urinary tract specimens in house. The laboratories reported processing various specimen types: voided urine, 735 of 738 (99.6%); bladder washing/barbotage, 639 of 738 (86.6%); and catheterized urine specimens, 653 of 738 (88.5%). Some laboratories used multiple preparation methods, but the most commonly used preparation techniques for urinary tract specimens were ThinPrep (57.4%) and Cytospin (45.5%). Eighty-eight of 197 laboratories (44.7%) reported preparing a cell block, but with a low frequency. Adequacy criteria were used by 295 of 707 laboratories (41.7%) for voided urine, and 244 of 707 (34.5%) assessed adequacy for bladder washing/barbotage. More than 95% of the laboratories reported the use of general categories: negative, atypical, suspicious, and positive. Polyomavirus was classified as negative in 408 of 642 laboratories (63.6%) and atypical in 189 of 642 (29.4%). One hundred twenty-eight of 708 laboratories (18.1%) performed ancillary testing, and of these, 102 of 122 (83.6%) reported performing UroVysion., Conclusions.—: Most laboratories use the ThinPrep method followed by the Cytospin technique; therefore, the criteria published in The Paris System for Reporting Urinary Cytology , based mostly on ThinPrep and SurePath, should be validated for Cytospin, and relevant information should be included in the revised edition of The Paris System for Reporting Urinary Cytology .

The Uniform Approach to Breast Fine Needle Aspiration Biopsy was put forward by a learned group of breast physicians in 1997. This landmark manuscript focused predominantly on diagnosis and reporting of mammary epithelial lesions. Today, most American practitioners turn initially to core biopsy rather than aspiration biopsy for the first line diagnosis of solid breast lesions; however, recent efforts from the International Academy of Cytology have produced a system called the Standardized Reporting of Breast Fine Needle Aspiration Biopsy Cytology (colloquially labeled in 2017 as the "Yokohama System"), suggesting a new interest in breast fine needle aspiration (FNA), especially in resource limited settings or clinical practice settings with experienced breast cytopathologists. Fibroepithelial lesions of the breast comprise a heterogeneous group of biphasic tumors with epithelial and stromal elements. Mesenchymal lesions of the breast include a variety of neoplasms of fibroblastic, myofibroblastic, endothelial, neural, adipocytic, muscular, and osteo-cartilaginous derivations. The cytology of mesenchymal breast lesions is infrequently described in the literature and is mainly limited to case reports and small series. This illustrated review highlights the cytologic features of fibroepithelial and mesenchymal mammary proliferations and discusses differential diagnoses and histomorphologic correlates., (© 2019 Wiley Periodicals, Inc.)

Although classical neurofibromas are commonly encountered skin lesions, histologic variants are infrequent. We report a greater than 15-year retrospective review of a single institution's experience with the histopathologic diagnosis of neurofibroma of the female breast with a focus on the hyalinized variant. An electronic histopathology record review (CoPathPlus; Cerner Corp, North Kansas City, MO) was conducted from January 1, 2000, to October 16, 2015, for all "neurofibroma" diagnoses rendered in "females" at the anatomical site "breast". All cases were microscopically revisited and subclassified into 1 of 10 histopathologic categories. Immunohistochemistry (IHC) for S100, tryptase, and CD117 were performed on 19 hyalinized and 19 age-matched classical neurofibromas. During the study period, 62,021 breast specimens were reviewed at our institution. Of these, 86 (0.14%) were diagnosed as neurofibromas. Subclassification was as follows: 50 classical (58%), 19 hyalinized (22%), 6 diffuse (7%), 5 cellular (6%), 3 myxoid (4%), 2 epithelioid (2%), and 1 plexiform (1%). All hyalinized and age-matched classical neurofibromas were S100 positive. The mean number of IHC-positive mast cells per high-power field (hpf) was 34.5 by tryptase and 26.8 by CD117 for the hyalinized subset and 22.5 by tryptase and 19.3 by CD117 for the classical cohort. Published literature reports a 2.6% incidence of hyalinized neurofibromas at nonspecial cutaneous sites. Our series details a 22% incidence in the breast. Regarding pathophysiology, there is a statistically significant increase in the average number of IHC-positive mast cells per hpf in hyalinized variants when compared with classical neurofibromas of the breast both by tryptase (P = 0.00157) and CD117 (P = 0.00901).

Background: Historically, sampling of adrenal lesions has been performed by percutaneous image-guided fine-needle aspiration (FNA) biopsy. Endoscopic ultrasound guided (EUS)-FNA of the adrenals was first employed at Cleveland Clinic ~10 years ago. We report a two-decade experience of adrenal FNA in our institution., Methods: An electronic retrieval identified adrenal FNAs from 1997 to 2017. Data points from each case (diagnosis, method of FNA, age, sex, laterality, needle gauge, size of lesion, adequacy of sample, and histologic follow up) were analyzed., Results: Our retrieval confirmed 198 adrenal FNAs performed over 20 years. Of these, 90% (179/198) were percutaneous, and the remaining 10% (19/198) were collected by EUS. Of the 179 CT guided FNAs, 93% (162/179) yielded an adequate specimen as compared with an adequacy rate of 89% (17/19) for EUS-FNAs, with no significant difference in adequacy rates by collection method, P = .64 (Fisher's exact). Of all adrenal FNAs, 53% (105/198) confirmed metastases, 33% (65/198) showed adrenal cells or primary adrenal neoplasms (85% cortical cells, 14% cortical neoplasia, 1% pheochromocytoma), 8% were inadequate (15/198), 3% were atypical (7/198), and 2% were suspicious for malignancy (5/198)., Conclusion: FNA of the adrenal glands can be useful in the diagnosis and staging of metastatic neoplasms, as well as in distinguishing primary adrenal cortical from medullary neoplasms and characterizing hematolymphoid and mesenchymal neoplasms. Overall adequacy rates for adrenal cytology are high (92%) with no statistically significant difference between CT-guided (93%) and EUS-FNA adequacy (89%). The majority of our procedures confirmed metastases, sparing patients unnecessary surgery., (© 2019 Wiley Periodicals, Inc.)

Background: The eighth edition of the American Joint Committee on Cancer staging manual (AJCC8) added depth of invasion to the definition of pathologic T stage (pT). In the current study, the authors assess pT stage migration and the prognostic performance of the updated pT stage and compare it with other clinicopathologic variables in patients with early squamous cell carcinoma of the oral tongue (OTSCC; tumors measuring ≤4 cm) with histologically benign lymph nodes (pN0)., Methods: A multi-institutional cohort of patients with early OTSCC was restaged as per AJCC8. Primary endpoints were local recurrence (LR) and locoregional recurrence (LRR). Influential variables were identified and an LR/LRR prediction model was developed., Results: There were a total of 494 patients, with 49 LR and 73 LRR. AJCC8 pT criteria resulted in upstaging of 37.9% of patients (187 of 494 patients), including 34.5% (64 of 185 patients) from pT2 to pT3, without improving the prognostication for LR or LRR. Both LR and LRR were found to be similar for patients with AJCC8 pT2 and pT3 disease. On multivariate analysis, LR was only found to be associated with distance to the closest margin (hazard ratio, 0.36; 95% CI, 0.20-0.64 [P = .0007]) and perineural invasion (hazard ratio, 1.92; 95% CI, 1.10-0.64 [P = .046]). Based on these 2 predictors, a final proportional hazards regression model (which may be used similar to a nomogram) was developed. The proposed model appeared to be superior to AJCC pT stage for estimating the probability of LR and LRR for individual patients with early OTSCC., Conclusions: AJCC8 pT criteria resulted in pT upstaging of patients with pN0 disease without improved LR or LRR prognostication. The proposed model based on distance to the closest margin and perineural invasion, status outperformed pT as a predictor of LR and LRR in patients with early OTSCC., (© 2019 American Cancer Society.)

Introduction: There are many merits to fine needle aspiration cytology (FNAC) in evaluation of palpable breast lesions. We set out to determine the concordance of breast FNAC interpretation with subsequent surgical pathology in the resource-limited healthcare setting of rural Kenya., Methods: African Inland Church Kijabe Hospital electronic pathology files were retrospectively reviewed from 1/1999-9/2017. All breast FNAC cases and subsequent surgical pathology specimens were identified. FNAC interpretations were categorised according to the International Academy of Cytology Yokohama codes: insufficient; benign; atypical favour benign; suspicious favour malignant; and malignant. Surgical pathology results were categorised as benign or malignant., Results: In total, 695 breast FNACs were identified. A total of 219 (31.5%) had subsequent surgical pathology. Average patient age was 39 years (range 13-88); 95% were female. Nearly all (98%) lesions were palpable. FNAC interpretive categorisation was as follows: 20 (9%) insufficient, 103 (47%) benign, 16 (7%) atypical, 24 (11%) suspicious and 56 (26%) malignant. On histopathology, there were 141 (64%) benign cases and 78 (36%) malignancies (Table 1). The sensitivity of FNAC for detecting malignancy was 85%; specificity was 75%. Positive and negative predictive values were 69% and 88%. Diagnostic concordance between FNAC and histopathology was 79%. For definitively diagnostic FNAC categories, diagnostic concordance was 89%. On histopathology, malignant diagnoses were given in 0 insufficient, 12 (12%) benign, 4 (25%) atypical, 11 (46%) suspicious and 51 (91%) malignant cases. There were five false-positive cytopathology interpretations and 12 false-negatives., Conclusions: FNAC remains a valuable tool in evaluation of palpable breast lesions in resource-limited healthcare settings., (© 2019 John Wiley & Sons Ltd.)

The 8th edition of American Joint Committee on Cancer (AJCC 8th) staging manual incorporated depth of invasion (DOI) into pT stage of oral cavity cancer. The aim of this study was to characterize several histological findings that may complicate measurement of DOI in early conventional squamous cell carcinomas (SCC) of the oral tongue: (1) lack of or minimal residual carcinoma following biopsy; (2) positive deep margin; (3) extratumoral perineural invasion (PNI); and (4) lymphatic or vascular invasion. Conventional SCC of the oral tongue (n = 407) with the largest dimension of ≤ 4 cm and with a negative elective cervical lymph node dissection (pN0) were reviewed. A clear plastic ruler was used to measure DOI by dropping a "plumb line" to the deepest point of the invasive tumor from the level of the basement membrane of the normal mucosa closest to the invasive tumor. Examples of identifying  reference point on the mucosal surface of oral tongue from which to measure the DOI are illustrated. In the experience of one contributing institution, the residual carcinoma was absent in 14.2% of glossectomies (34/239), while in 4.8% of cases (10/205) there was only minimal residual carcinoma. In 11.5% (21/183) of pT2 cases the deep margin was positive and thus DOI and pT may be underestimated. Of all cases with PNI, extratumoral PNI was identified in 23.1% (31/134) of cases, but represented the deepest point of invasion in only two cases. In one case, lymphatic invasion represented the deepest point of invasion and could have led to upstaging from pT1 to pT2. In conclusion, DOI measurement for SCC of the oral tongue may require re-examination of the diagnostic biopsy in up to 20% of cases due to the absence or only minimal residual carcinoma in glossectomy specimens. In 11.5% of apparently pT2 cases, DOI may be underestimated due to the positive deep margin. Rarely, extratumoral PNI or lymphatic invasion may be the deepest point of invasion. Overall, two issues (absent or minimal residual disease and positive deep margin) may confound DOI measurement in early SCCs of oral tongue.

Mammary ductal carcinoma in situ (DCIS) is classically treated by combinations of excision, radiation, and endocrine therapy, based upon the specific needs of individual patients. Estrogen receptor (ER) status is generally assessed by immunohistochemistry (IHC) in newly diagnosed cases of DCIS, and endocrine therapy in this setting is thought to be chemopreventive. The potential impact of androgens on mammary carcinogenesis has been studied in recent years, and several authors have proposed androgen receptor (AR) IHC testing and targeted antiandrogenic therapy in patients with locally advanced or metastatic triple-negative invasive breast cancer (ie, negative for ER and progesterone receptor and HER-2). Very little has been published on AR in DCIS. We report results of AR IHC on archival tissue blocks from 221 adult female patients, each of whom underwent definitive breast resection of DCIS. Of the 221 cases, 72 (33%) were shown to express AR in their DCIS at or above the 10% threshold often used for invasive carcinoma. AR expression was seen in all grades of DCIS. Of the 72 positive AR cases, 21 (29%) were ER negative, corresponding to 10% (21/221) of all patients. The majority of the AR-positive cases were high grade, and the most common histologic subtype in this subset was a solid growth pattern with apocrine features. Early data from clinical trials evaluating AR antagonists in invasive/metastatic triple-negative breast cancer suggest that some patients may benefit from androgen blockade. IHC testing and potential clinical trials of AR antagonists for chemoprevention in patients with AR-positive and ER-negative DCIS could be considered.

Objectives: Cryptococcal meningoencephalitis is the most common fungal infection of the central nervous system diagnosed by cerebrospinal fluid cytology (CSF) studies. Existing literature suggests that routine CSF cytomorphologic evaluations are exquisitely specific; however, less is known about their sensitivity., Methods: An electronic record review of the cytopathology and microbiology files was conducted for the 21-year interval from January 1, 1995, through December 31, 2015., Results: In 21 years, 12,584 CSF samples were processed in the laboratory. Of these, 24 (0.2%) were reported positive for cryptococcal organisms by light microscopy, and 129 CSF fungal cultures were positive for Cryptococcus species. All cotested specimens with positive cytology results were positive on culture (15 specimens, 100% specificity). Twenty-four samples with positive culture results were negative by CSF cytology (sensitivity 39%)., Conclusions: When culture is used as a gold standard, CSF cytology is 100% specific and 39% sensitive, with a positive predictive value of 100% and a negative predictive value of 99.8%.

Granulomatous mastitis is an uncommon inflammatory disease that typically presents with painful breast lesions. Recent publications have brought to light a specific subset of granulomatous mastitis patients with a distinct histological pattern of disease termed, "cystic neutrophilic granulomatous mastitis" (CNGM). Although many cases of granulomatous lobular mastitis have been thought to be idiopathic, this rare subset of an uncommon disease has been linked to infections with Corynebacterium species. Herein, a cohort of CNGM patients from a large, tertiary care, North-American, academic medical center is presented. Correlative demographic, clinical, radiographic, pathologic, microbiologic, management, and outcomes data are provided. Collaborative communication between specialists to accurately diagnose and manage these patients is essential to decreasing potential morbidity., (© 2018 Wiley Periodicals, Inc.)

Background: The long-term risk for patients with benign intraductal papillomas (IDPs) on core needle biopsy (CNB) who are not upgraded on excision is not well-defined. The goal of this study was to determine the cumulative breast cancer (BC) incidence for patients with benign IDP on CNB., Materials and Methods: There were 152 benign IDPs diagnosed on CNB between 2003 and 2008. Radiology and pathology data were reviewed by breast radiologists and pathologists. Clinical follow-up was obtained from the electronic medical record (Epic)., Results: Excision results were: 96 (63%) not upgraded, 9 (6%) with BC on excision (6 ductal carcinoma in situ, 3 invasive carcinoma), and 5 (3%) lacked correlation with the CNB site. Excision reports were unavailable for 42 (28%). Excluding cases with Breast Imaging Reporting and Data System (BI-RADS) 5 or discordant imaging, there were 6 (4%) true upgrades (all ductal carcinoma in situ). After the exclusion of patients with other major risk factors, follow-up was available for 55 of 58 patients with benign IDPs, and 8 (14%) developed BC after a median of 112 months (range, 11-159 months). None of the benign IDP patients without an excision report developed BC after a median of 97 months (range, 5-164 months)., Conclusions: The upgrade rate for benign IDP diagnosed on CNB was 4%, similar to recent studies. The cumulative BC incidence for those who were not upgraded and who had no history of BC was 14% at a median of 9 years. When combined with patients without an excision pathology report, the overall BC incidence was 9%. The findings support continued breast cancer surveillance in this patient population., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The Revised fourth Edition World Health Organization (WHO) Classification of Tumors of Hematopoietic and Lymphoid Tissues suggests novel categories, including "high grade B-cell lymphoma with MYC and BCL2 and BCL6 gene rearrangements." These diseases are known colloquially as "double hit" and "triple hit" lymphomas. The "first-hit" in these cases is the harboring of a MYC rearrangement. Concurrent derangements of BCL2 and BCL6 can be the "second-hit" or "third-hit." To our knowledge, this is the first report of "triple-hit" lymphomas in cytology specimens. The files of the Cleveland Clinic (January 2007 through December 2017) were searched for all "triple hit" lymphomas. Four cases met inclusion criteria (cytology slides in files and histologically confirmed "triple hit" lymphoma). All slides were reviewed. The mean age was 65 years, with a male predominance. All patients presented at advanced stage and showed progressive disease despite therapy. FISH studies (histologic sections) confirmed translocations of MYC (8q24), BCL2 (18q21) and BCL6 (3q27) in all patients. All cases were characterized by high cellularity, dispersed cells, presence of stripped nuclei, lymphoglandular bodies, apoptotic bodies, cytomegaly, nucleomegaly, nuclear envelope irregularities, macronucleoli (most often single), recognizable mitoses and presence of cytoplasmic vacuoles (variable). The WHO recommends that all large B-cell lymphomas be investigated using cytogenetic or molecular techniques. Concurrent inhibition of MYC and BCL2 is a potentially effective treatment strategy for triple hit lymphomas, and an expanding literature exists regarding predictive biomarkers and therapeutic regimens. It is our intention to raise awareness of this uncommon mature B-cell neoplasm within the cytodiagnostic community., (© 2018 Wiley Periodicals, Inc.)

Plexiform fibromyxoma (PF) is a recently-described and rare mesenchymal neoplasm of the gastric wall. A few small case series reports of this spindle cell entity exist in the surgical pathology literature, but to our knowledge no prior endoscopic ultrasound guided fine needle aspiration cytology examples have been reported. In clinical practice, mural gastrointestinal (GI) lesions are often initially evaluated by endoscopic ultrasound guided (EUS) fine needle aspiration (FNA). In addition, newer EUS fine needle biopsy techniques also allow for reliable retrieval of core tissue samples with intact cellular architecture, making EUS histopathologic analyses possible. We report a combined EUS FNA and core biopsy case of PF and correlate the findings with imaging results. The cytomorphology of PF is described and illustrated, and important entities in the differential diagnosis of upper GI spindle cell lesions (including GI stromal tumor, leiomyoma, schwannoma, carcinoid tumor, desmoid-type fibromatosis, and inflammatory fibroid polyp) are reviewed. Illustrated examples of relevant cytomorphologic, cell block histomorphologic and immunohistochemical characteristics are emphasized., (© 2018 Wiley Periodicals, Inc.)

Background: Breast cancer risk estimates for atypical lesions are based primarily on case-control studies of patients with open biopsies. The authors report the cumulative breast cancer incidence after a core biopsy diagnosis of atypical hyperplasia (ductal or lobular) or lobular carcinoma in situ., Methods: A cohort study with central pathology review was conducted on 393 patients who had core biopsy diagnoses of atypical hyperplasia and lobular carcinoma in situ from 1995 through 2010. Follow-up was available for 255 of 264 patients (97%) at a median of 87 months (range, 3-236 months)., Results: There were 212 patients (54%) who were not upgraded on excision and had no personal history of breast cancer. Of these, 21 of 212 (9.9%) developed breast cancer, including 15 invasive carcinomas, 4 ductal carcinomas in situ, 1 pleomorphic lobular carcinoma in situ, and 1 unknown type. The prior core biopsy diagnoses were atypical ductal hyperplasia for 11 patients (52%) and atypical lobular hyperplasia/lobular carcinoma in situ in the remaining 10 patients (48%). The number of atypical foci in the core biopsy was not significantly associated with the subsequent development of breast cancer (P = .42). Of the 15 invasive carcinomas, 11 (73%) were ipsilateral, 11 (73%) were pathologic T1 tumors, 5 (33%) were pathologic N1 tumors, 13 (87%) were estrogen receptor-positive, and 1 (7%) was amplified for human epidermal growth factor receptor 2., Conclusions: In patients who had an initial diagnosis of atypical hyperplasia or lobular carcinoma in situ on core biopsy, the 7-year cumulative breast cancer incidence was 9.9%. Most tumors were ipsilateral, stage I, estrogen receptor-positive, invasive carcinomas. The current data support close clinical and radiologic follow-up for more than 5 years in this patient population. Cancer 2018;124:459-65. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Background: The incidence of anal carcinoma has risen in recent decades. Exfoliative cytology screening of selected high risk patients is performed in many centers. Unsatisfactory cytology results are frustrating to patients, clinicians, and laboratorians. The aim of this study is to ascertain outcomes of patients with non-diagnostic anal cytology., Methods: A retrospective review of anal cytology testing performed at the Cleveland Clinic between 01/01/2001 and 12/31/2015 was performed. All cases were received as liquid-based samples and processed as ThinPreps (Hologic, Marlborough, MA). Co-testing for HR-HPV DNA was performed using Hybrid Capture 2® (Qiagen, Germantown, MD) in the majority of patients., Results: Of 1,276 ThinPrep anal cytology samples, 130 (10%) were deemed unsatisfactory. 77% of patients were HIV positive. 85% were males. Of the unsatisfactory cases, 116 (89%) were co-tested for HR-HPV DNA. Of those, 40 patients (34%) had a simultaneous positive HR-HPV DNA. Adequate follow up cytology within a one year and a two year period revealed that 18/130 (14%) and 26/130 (20%) of patients had ASC or SIL respectively. Histologic follow-up within one and two years showed 3 patients (2%) and 8 patients (6%) with HSIL or worse., Conclusions: High risk patients with unsatisfactory anal cytology are not "negative". At least one-third proved to be concomitantly HR-HPV DNA positive with one-fifth showing subsequent cytologic squamous abnormalities and with more than 5% being diagnosed with a high grade intraepithelial lesion within two years. Prompt repeat cytology and/or HR-HPV DNA is recommended for high risk patients with non-diagnostic cytology., (© 2017 Wiley Periodicals, Inc.)