Fluorescent in-situ hybridization test performed on cell blocks is useful for establishing germ cell origin of metastatic tumors with unusual clinical presentation.

The majority of germ cell tumors (GCTs) are characterized by iso-chromosome 12p (i12p) abnormality. The aim of this study is to review the cytomorphologic features and analyze the utility of i12p fluorescent in-situ hybridization (FISH) test in diagnosing metastatic GCTs primarily evaluated by cytologic techniques in patients without prior history of GCTs. The laboratory information system was queried over a period of 10 years to search for cases where i12p FISH test was requested on cytology material. FISH test was performed using TelVysion 12p telomeric probe and CEP 12 centromere probe on cell-blocks. A ratio of 12ptel/CEP12 signal of 1.4 or greater was considered as positive. Patient demographics, clinical presentation, cytopathologic findings, and follow-up surgical resection data were reviewed and correlated. A total of three cases were identified, all men (age range 31-60 years). Cytologic diagnoses were favor metastatic embryonal carcinoma (Case 1, retroperitoneal fluid FNA), metastatic yolk sac tumor/YST (Case 2, lung mass FNA) and adenocarcinoma, likely representing a somatic-type malignancy (SM) arising from a preexisting GCT (Case 3, retroperitoneal mass FNA). This limited study demonstrated high sensitivity for detecting i12p abnormality by FISH test performed on cell blocks. The cytomorphology of extra-gonadal GCTs varies according to the histologic subtype. Sarcomatoid morphology of YST, SM or mixed GCTs further complicates cytology evaluation. FISH test for detection of i12p performed on cell-blocks is extremely useful in establishing germ cell origin of these metastatic GTCs with unusual cytomorphology and guides management in patients without prior history of GCTs.

Is Milan for kids?: The Milan System for Reporting Salivary Gland Cytology in pediatric patients at an academic children's hospital with cytologic-histologic correlation.

BACKGROUND: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) provides a useful framework for the diagnosis of salivary gland fine-needle aspiration (FNA) biopsies. In this study, the MSRSGC was applied to salivary gland FNAs in pediatric patients to assess its usefulness and look at pitfalls. METHODS: The laboratory information system was queried over a 15-year period for all salivary gland FNAs in patients 18 years old or younger. Patient demographics, FNA diagnosis categorized according to the MSRSGC, and follow-up surgical pathology diagnoses were examined and correlated. RESULTS: Thirty-two cases were identified, with an average age of 12 years (range, 0.6-18 years). A majority of the cases (84.4%) were from the parotid region. Twenty of 32 cases (62.5%) had follow-up resection. MSRSGC recategorization diagnoses of the 32 FNA cases were 34% benign neoplasm, 31% nonneoplastic, 16% nondiagnostic, 9% atypia of undetermined significance, 3% salivary neoplasm of uncertain malignant potential, 3% suspicious for malignancy, and 3% malignant. Overall, the sensitivity and specificity were 100% and 80%, respectively. On follow-up resection, 55% were neoplastic: pleomorphic adenomas (n = 6; 55%), pilomatricoma (n = 3; 28%), mucoepidermoid carcinoma (n = 1; 9%), schwannoma (n = 1; 9%), and myofibroma (n = 1; 9%). CONCLUSIONS: The MSRSGC performed fairly well in the pediatric population with a low overall risk of malignancy (6%) and high sensitivity. Although the majority of pediatric salivary gland FNAs were benign, 55% of resected cases were positive for a neoplasm, with benign neoplasms outnumbering malignancy. Challenging entities included inflammatory conditions, like immunoglobulin G4-related sialadenitis, and skin and soft tissue lesions near the salivary gland.

Thyroid paraganglioma: A diagnostic pitfall in thyroid FNA.

BACKGROUND: Thyroid paragangliomas are extremely rare and often are misdiagnosed by preoperative fine-needle aspiration (FNA) because their cytologic features overlap with those of other thyroid neoplasms. The objective of this study was to review the cytomorphology in a series of thyroid paragangliomas and correlate the findings with histopathology. METHODS: Five thyroid paraganglioma cases that underwent FNA were reviewed. Their clinical presentation, radiology features, cytomorphology, ancillary tests, and histopathology were analyzed. RESULTS: All patients were women with an average age of 49 years (age range, 35-61 years) and presented with an asymptomatic, solitary thyroid nodule. Radiologically, these nodules (size range, 1.8-3.0 cm) were well circumscribed, hypoechoic, and hypervascular. FNA smears showed clusters of loosely cohesive, medium-to-large epithelioid cells with clear-to-eosinophilic and occasionally foamy cytoplasm that had indistinct cytoplasmic borders. The nuclei were round to oval with focal nuclear membrane irregularities, inconspicuous nucleoli, focal marked anisonucleosis, and occasional intranuclear pseudoinclusions. Naked nuclei, variable numbers of plasmacytoid cells, multinucleated giant cells, and sustentacular cells were present in the background along with blood vessels and lymphocytes. Cytology diagnoses were incorrect and included follicular neoplasm (n = 4) and follicular lesion of undetermined significance (n = 1). Final histopathology with immunohistochemistry revealed conventional paraganglioma (n = 3) or sclerosing paraganglioma with invasive features (n = 2). CONCLUSIONS: All thyroid paragangliomas were misdiagnosed on FNA as follicular neoplasms, in part because of the rarity of these tumors in this location and cytomorphology mimicking follicles. The absence of colloid, the presence of naked nuclei, focal marked anisonucleosis, and the presence of sustentacular cells are important cytology clues.

Ki-67 proliferation index in neuroendocrine tumors: Can augmented reality microscopy with image analysis improve scoring?

BACKGROUND: The Ki-67 index is important for grading neuroendocrine tumors (NETs) in cytology. However, different counting methods exist. Recently, augmented reality microscopy (ARM) has enabled real-time image analysis using glass slides. The objective of the current study was to compare different traditional Ki-67 scoring methods in cell block material with newer methods such as ARM. METHODS: Ki-67 immunostained slides from 50 NETs of varying grades were retrieved (39 from the pancreas and 11 metastases). Methods with which to quantify the Ki-67 index in up to 3 hot spots included: 1) "eyeball" estimation (EE); 2) printed image manual counting (PIMC); 3) ARM with live image analysis; and 4) image analysis using whole-slide images (WSI) (field of view [FOV] and the entire slide). RESULTS: The Ki-67 index obtained using the different methods varied. The pairwise kappa results varied from no agreement for image analysis using digital image analysis WSI (FOV) and histology to near-perfect agreement for ARM and PIMC. Using surgical pathology as the gold standard, the EE method was found to have the highest concordance rate (84.2%), followed by WSI analysis of the entire slide (73.7%) and then both the ARM and PIMC methods (63.2% for both). The PIMC method was the most time-consuming whereas image analysis using WSI (FOV) was the fastest method followed by ARM. CONCLUSIONS: The Ki-67 index for NETs in cell block material varied by the method used for scoring, which may affect grade. PIMC was the most time-consuming method, and EE had the highest concordance rate. Although real-time automated counting using image analysis demonstrated inaccuracies, ARM streamlined and hastened the task of Ki-67 quantification in NETs.