Faculty Bibliography

OBJECTIVES/OBJECTIVE:Our study assesses whether the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) offers any benefit over the original cytology classification, and measures interobserver agreement. METHODS:Four cytopathologists retrospectively blindly classified preoperative cytology by MSRSGC from 101 resected salivary tumors. Consensus MSRSGC diagnoses were correlated with surgical pathology diagnoses and compared with the original cytology classification. Diagnostic parameters were calculated for both systems. Interobserver variability was assessed. RESULTS:The original cytology classification vs MSRSGC had sensitivity, specificity, positive predictive value, and negative predictive value of 75.0% vs 78.3%, 97.1% vs 98.0%, 91.2% vs 94.7%, and 90.1% vs 90.0%, respectively. The original cytology classification risk of neoplasm (RON) was 91.7% for "negative for malignancy" and 100.0% for other categories. The MSRSGC RON was 71.4% in category II (nonneoplastic) and 100.0% in all other categories. The original cytology classification risk of malignancy (ROM) ranged from 0.0% for "atypical" to 100.0% for "positive for malignancy." The MSRSGC ROM ranged from 0.0% in categories I (nondiagnostic) and III (nonneoplastic) to 100.0% in category VI (malignant). Weighted agreement using the MSRSGC was 92% (Gwet AC1, 0.84); unweighted agreement was 69% (Gwet AC1, 0.64). MSRSGC category IVA (benign neoplasm) was most likely to show interobserver agreement, with complete agreement in 67% of cases. CONCLUSIONS:The MSRSGC performs similarly to the original cytology classification and shows relatively high interobserver agreement.

Myoepithelial carcinoma (MEC) of soft tissue, also known as malignant myoepithelial tumor, is an uncommon malignancy. Cytologic diagnosis of this entity is challenging due to its rarity and heterogeneous morphology. We report a case of MEC in a 22-year-old man, who presented with a 6.5 cm soft tissue mass on his right distal forearm that has been enlarging over the past 3 months. Ultrasound-guided fine-needle aspiration (FNA) revealed abundant isolated neoplastic cells ranging from spindled cells to epithelioid and plasmacytoid morphology in a myxoid background. These cells showed moderate cytologic atypia characterized by high-nuclear/cytoplasmic ratio, irregular nuclear contours, and prominent nucleoli. The cytoplasm varied from dense to vacuolated and occasionally rhabdoid with intracytoplasmic inclusions. Scattered bi- and multinucleated cells were identified. A diagnosis of high-grade malignancy was made with the differential diagnosis including rhabdomyosarcoma and melanoma. A subsequent core biopsy of the tumor showed immunoreactivity for pan-cytokeratins, calponin, p63, and smooth muscle actin. INI-1 was lost. SOX-10 and Melan-A were negative. Molecular studies showed loss of SMARCB1 (INI-1) and CDKN2A. Gene fusion studies did not detect any fusion. A diagnosis of soft tissue MEC was made which is a challenge on FNA due to several cytologic mimickers including rhabdomyosarcoma, epithelioid sarcoma, extrarenal rhabdoid tumor, extra-axial chordoma and melanoma. Recognition of the biphasic cell population in a myxoid background and a battery of immunohistochemical stains are crucial for accurate diagnosis.

We report two cases of an uncommon benign lesion, retroperitoneal ganglioneuroma, first diagnosed on fine needle aspiration (FNA) cytology. Our first case presented with nausea, constipation, vomiting, and neutropenia after three cycles of chemotherapy for breast cancer treatment, while our second patient presented with seemingly unprovoked abdominal pain and progressive neuropathy. Both underwent computed tomography (CT) scans, in which a soft tissue mass was found in the retroperitoneal space in each patient. An endoscopic ultrasound guided (EUS) FNA was performed on both patients, and as a result, the masses were diagnosed as retroperitoneal ganglioneuromas. As retroperitoneal ganglioneuromas have low incidence of proliferation, invasive surgery was avoided in favor of routine follow-up imaging. Cytologically, both masses showed large, scattered ganglion cells with abundant cytoplasm and large nuclei against a background of wavy spindle cells with elongated nuclei. Histologically, both were positive for S-100. When an EUSFNA is performed and quality material is collected, a diagnosis of retroperitoneal ganglioneuroma may be established, preventing invasive surgery and its accompanying risks in favor of routine follow-up imaging.

INTRODUCTION/BACKGROUND:The American College of Radiology (ACR) Thyroid Imaging Reporting and Data Systems (TI-RADS) was developed to standardize thyroid ultrasound reports and predict the likelihood of malignancy. In our study, we aimed to correlate indeterminate thyroid fine needle aspiration cytology cases with preceding ultrasound (US) ACR TI-RADS scores and concurrent molecular testing results to examine how well the use of the ACR TI-RADS in our institution predicted which patients with indeterminate cytology might harbor molecular alterations. MATERIALS AND METHODS/METHODS:We performed a retrospective review of thyroid nodules. Patients with US reports that included TI-RADS scores, fine needle aspiration specimens with indeterminate cytology (Bethesda class III-V), and molecular testing results were included. RESULTS:A total of 46 indeterminate cytology cases had had preceding US reports with TI-RADS scores and molecular testing (Bethesda class III, n = 37; Bethesda class IV, n = 6; Bethesda class V, n = 3). Most of the indeterminate cases had had a TI-RADS score of TR4 (31 of 46; 67.39%) or TR5 (9 of 46; 19.57%). RAS mutations were the most common alteration (n = 12). Of the 46 cases, 22 (47.85%) showed no alterations. Ten cases proceeded to surgery, of which seven displayed malignancies. CONCLUSIONS:Molecular testing in cytologically indeterminate thyroid nodules provided valuable information for TR4 and TR5 lesions; however, the TR2 and TR3 lesions often had no molecular alterations. These findings highlight the potential value of including US imaging features when assessing the significance of indeterminate cytology findings.

BACKGROUND:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for coronavirus disease 2019 (COVID-19), is known to cause severe respiratory infections with occasional accompanying pleural effusion (PE), pericardial effusion (PCE), or peritoneal effusion (PTE). The effect of COVID-19 on effusion cytology is not yet known. This study aimed to examine the cytomorphologic features and workup of effusion fluids in patients with active COVID-19 infection versus those in recovery. METHODS:PE (n = 15), PCE (n = 1), and PTE samples (n = 20) from hospitalized patients with a SARS-CoV-2 infection (from June 1, 2020, to December 30, 2020) were reviewed. Effusion fluids with metastatic carcinoma were excluded. Differential cell counts, cytomorphology, and relevant immunostains for effusion fluids were retrospectively evaluated and compared between patients with active infection (positive on a SARS-CoV-2 nucleic acid amplification test [NAAT] within 2 months; n = 23) and those in the recovery phase from COVID-19 (negative on a SARS-CoV-2 NAAT for >2 months; n = 13). RESULTS:The cytology diagnoses were negative for malignancy (n = 31), atypical (n = 4), and suspicious for malignancy (n = 1). Active infection cases showed more atypical mesothelial cells than recovery cases (P < .05); some had enlarged nuclei, prominent nucleoli, occasional multinucleation, and bizarre nuclei. Immunostains were performed more often in active infection cases than recovery cases (47.8% vs 7.7%; P < .05). Differential cell counts (available for 28 cases) showed no significant differences between the active infection and recovery groups. CONCLUSIONS:This study found atypical and bizarre mesothelial cells more often in effusions of cases with active COVID-19 infection in comparison with patients in recovery. It is important for cytopathologists to become familiar with the cytomorphologic effects of SARS-CoV-2 on effusion cytology so that these cases can be properly triaged.

Glomus tumors make up 1% of stromal tumors of the stomach. Radiologic diagnosis of glomus tumors can be challenging as they share imaging characteristics with other neuroendocrine tumors and gastrointestinal stromal tumors. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has been reported as a useful method for the evaluation of gastrointestinal lesions. We report two cases of gastric glomus tumors in which EUS-FNA diagnosis was challenging. Cytologically, neoplastic cells were round to oval, uniform, bland appearing epithelioid cells with delicate chromatin and inconspicuous to vague nucleoli. Both samples lacked worrisome features such as high nuclear grade, high mitotic rate, and necrosis. Neoplastic cells were negative for Cam5.2 and AE1/AE3 with focal expression of synaptophysin in one of the cases. A definitive diagnosis was not made based on FNA. Familiarity with glomus tumors in the GI system and procurement of adequate material for cell block allowing the use of immunohistochemistry may allow an accurate preoperative diagnosis.

Importance/UNASSIGNED:Genomic classifiers were developed to better guide clinicians in the treatment of indeterminate thyroid nodules (ITNs). To our knowledge, whether there is variation in the diagnostic accuracy of these tests depending on ITN size has not been previously studied. Objective/UNASSIGNED:To analyze the diagnostic performance of a genomic classifier in relation to ITN size. Design, Setting, and Participants/UNASSIGNED:A case series study with medical records review was conducted including all patients with a cytologic diagnosis of ITN managed with genomic classifier testing and surgery from January 2015 to December 2018 at NYU Langone Health. Demographics, ITN characteristics, genomic profiles, treatment, and final pathologic findings were recorded. Data analysis was conducted from March to April 2021. Main Outcomes and Measures/UNASSIGNED:The primary aim was to assess the positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity of a genomic classifier test (ThyroSeq) in relation to ITN size (<2, 2-4, and >4 cm). The secondary aim was to investigate the risk of cancer associated with genetic signatures. Results/UNASSIGNED:Of the 212 patients with 218 ITNs, 158 (74.5%) were women; median (SD) age was 49 (15.6) years. Genomic classifier results were positive in 173 ITNs (79.4%) treated with surgery. In this group of 173 positive ITNs, 46 (26.6%) were malignant on final pathologic testing. Overall, the observed cancer prevalence in the population was 23.9% (52 ITNs). In 45 ITNs that underwent surgery despite a negative genomic classifier interpretation, 6 (13.3%) were malignant. The PPV of a positive test was 27% and the NPV was 87%. The PPV and NPV findings improved as the ITN size increased (<2 cm [n = 98]: PPV, 25%; NPV, 79% vs >4 cm [n = 33]: PPV, 50%; NPV, 89%). Test specificity was higher in larger ITNs (<2 cm: 15% vs >4 cm: 40%; P = .01). Isolated RAS sequence variations were the most common variant identified in malignant nodules (11 [21.1%] of all ITNs), followed by BRAF variants (7 [13.5%] of all ITNs). Conclusions and Relevance/UNASSIGNED:In this case series, the performance of the ThyroSeq test improved for larger ITNs. The risk of cancer in large ITNs with negative test results was low. These data suggest that, in genomic classifier-negative ITNs larger than 4 cm, initial management of thyroid lobectomy may be sufficient.