Editorial: Optimizing Schools of Cytology: Discussions from the 2022 ASC/IAC Cytology Education Symposium, North American Strategies, and European Symbiosis.

This report highlights information and outcomes from the November 2022 ASC/IAC joint Cytology Education Symposium, an annual conference organized by the Cytology Programs Review Committee. The manuscript provides information on shared educational opportunities and practices for cytology students and other learners in anatomic pathology, discusses recruitment strategies for schools of cytology, conveys teaching resources, introduces perspectives on virtual microscopy and online learning, and transmits information about wellness of students in schools of cytology.

Optimizing schools of cytology: Discussions from the 2022 ASC/IAC Cytology Education Symposium, North American Strategies, and European Symbiosis.

This report highlights information and outcomes from the November 2022 ASC/IAC joint Cytology Education Symposium, an annual conference organized by the Cytology Programs Review Committee. The manuscript provides information on shared educational opportunities and practices for cytology students and other learners in anatomic pathology, discusses recruitment strategies for schools of cytology, conveys teaching resources, introduces perspectives on virtual microscopy and online learning, and transmits information about wellness of students in schools of cytology.

The spectrum of malignant diagnoses in cerebrospinal fluid cytology from an adult population: a multi-institutional retrospective review.

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.

Liver Mass as First-Time Diagnosis of Sarcomatoid Anaplastic Thyroid Carcinoma: A Rare Malignancy Presenting at an Unexpected Body Site.

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.

Ductal Carcinoma Arising in a Squamous Epithelial Inclusion Cyst within an Axillary Lymph Node: A Challenging Nodal Metastasis.

Introduction. Assessment of axillary lymph nodes in breast carcinoma is an important part of staging to guide appropriate clinical management. Lymph node inclusions of different types, including nevoid, squamous, and glandular, are rare but have been reported in multiple different anatomic locations including the axilla. These can result in diagnostic challenges and pose risks of misdiagnoses. Rarely, malignancies may arise intrinsic to otherwise incidental benign nodal inclusions. Case Presentation. We report a case of ductal carcinoma diagnosed within a squamous epithelial inclusion cyst within an axillary lymph node in a patient with pure ductal carcinoma in situ (DCIS) of the ipsilateral right breast. To our knowledge, this is the fifth report in the literature of breast carcinoma confirmed within an axillary inclusion in a patient with pure DCIS. Evaluation of the primary DCIS and lymph node inclusions, by routine and immunohistochemical stains, was performed for assessment. Discussion. The presence of lymph node inclusions can pose a challenge in assessment of benignity and malignancy, on frozen and permanent histologic sections. Pathologists should carefully evaluate lymph node inclusions to ensure that intrinsic malignancies are not missed within rare otherwise benign appearing incidental epithelial rests.

Evaluation of automated sample preparation system for lymph node sampling.

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.

Remotely operated robotic microscopy for rapid diagnosis of bronchoscopic cytology specimens.

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.

TRPS1 outperforms GATA3 in pleural effusions with metastatic breast carcinoma versus mesothelioma.

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.

Low-grade adenosquamous carcinoma of the breast: a clinical, morphological and immunohistochemical analysis of 25 patients.

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.

Lymphangioleiomyomatosis in lymph node cytology: Another "Floating Island" to visit.

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.

Malignant rhabdoid tumor: Cyto-histologic correlation and immunohistochemical characterization of a rare pediatric malignancy and its differential diagnoses.

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.

Multiple Consecutive Cervicovaginal Cytology Specimens Confirm Persistent Colonization by Cokeromyces recurvatus: Case Report and Literature Review.

The published literature on cervicovaginal cytology includes fewer than ten reported cases of Cokeromyces recurvatus identified in Pap test samples. We report a unique case of an asymptomatic 27-year-old female with persistent gynecologic tract colonization by C. recurvatus in which distinctive fungal microorganisms were identified in three samples collected over three consecutive years.

Cyto-histologic correlation of crystal-storing histiocytosis: Rare presentation in breast, predating diagnosis of B-cell lymphoma by two years.

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.

Biphasic squamoid alveolar renal cell carcinoma: Cytologic features of a rare entity.

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).

Mammary analogue secretory carcinoma: A challenging case arising in a young man with radiation exposure.

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.

Malignant gastrointestinal neuroectodermal tumor: Cytologic, histologic, immunohistochemical, and molecular pitfalls.

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.

Laboratory Medicine and Pathology Education During the COVID-19 Pandemic-Lessons Learned.

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.

Eccrine angiomatous hamartoma: First case in the cytology literature.

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.