BACKGROUND: ThyroSeq assesses the probability of malignancy (POM) in thyroid fine-needle aspiration cytology specimens diagnosed as atypia of undetermined significance (AUS). The authors investigated whether defined AUS subcategories are associated with specific molecular alterations, the molecular-derived risk of malignancy (MDROM), and the risk of malignancy (ROM). METHODS: Fine-needle aspiration cytology reports of AUS and corresponding results from the ThyroSeq version 3 genomic classifier results were retrieved and subcategorized as follicular cells with either cytologic atypia (FC-C), architectural atypia (FC-A), both cytologic and architectural atypia (FC-CA), or a predominance of Hurthle cells (PHC). The MDROM, ROM, and frequency of molecular alterations by subcategory were computed and analyzed, and p < .05 was considered significant. RESULTS: The final analysis included 541 cases subdivided into 233 with FC-A, 104 with FC-C, 116 with FC-CA, and 88 with PHC. The benign call rate and positive call rate for the AUS category were 72% and 28%, respectively, which varied between AUS subcategories. The MDROM by subcategory was 15.9% FC-A, 20.5% FC-C, 33.8% FC-CA, and 14.4% PHC. Histologic follow-up was available for 155 (28%) AUS cases with a follow-up period ≥12 months. The 95% confidence intervals of the MDROMs overlapped with the ROMs. The highest MDROM and ROM were in the FC-CA subcategory. RAS mutations were present in all subcategories. BRAF V600E mutations and papillary thyroid carcinoma were most frequent in the FC-CA subcategory. Noninvasive follicular thyroid neoplasm with papillary-like nuclear features was significantly more frequent in the FC-C subcategory. CONCLUSIONS: The current results demonstrated that AUS subcategories are associated with specific genetic alterations, the MDROM, and the ROM. Molecular results and an awareness of various cancer probabilities within AUS subcategories can allow for a more tailored management. Cancer Cytopathol 2022;
Follicular lymphoma (FL) is one of the most frequently diagnosed lymphomas in the United States and Europe. The definition of and basic approach to diagnosis and grading of FL is essentially unchanged in the recently updated revision of the World Health Organization (WHO) classification. FL is a biologically and histopathologically heterogeneous disease. Although there is an improved understanding of some FL variants and specific subtypes, there are cases whose recognition is particularly challenging, either because they have unusual features or represent examples of new or rare variants. Herein, we share a series of unusual and difficult to recognize FLs with the goal of increasing awareness of the expanding histopathologic variability in FL. Unusual FL discussed here include: FL with Castleman-like changes, FL with plasmacytic differentiation, and immunoglobulin G4-positive plasma cells in the setting of immunoglobulin G4-related disease, FL with marginal zone differentiation and involving mucosa-associated lymphoid tissue sites, diffuse FL variant expressing CD23 with STAT6 mutation, large B-cell lymphoma with IRF4 rearrangement, CD10-negative and MUM1-positive aggressive FL, and Epstein-Barr virus–positive FL.
Objectives We aimed to determine the interobserver reproducibility in diagnosing low-grade ductal carcinoma in situ (DCIS). We also aimed to compare the interobserver variability using a proposed two-tiered grading system as opposed to the current three-tiered system. Methods Three expert breast pathologists and one junior pathologist identified low-grade DCIS from a set of 300 DCIS slides. Months later, participants were asked to grade the 300 cases using the standard three-tiered system. Results Using the two-tiered system, interobserver agreement among breast pathologists was considered moderate (κ = 0.575). The agreement was similar (κ = 0.532) with the junior pathologist included. Using the three-tiered system, pathologists’ agreement was poor (κ = 0.235). Conclusions Pathologists’ reproducibility on diagnosing low-grade DCIS showed moderate agreement. Experience does not seem to influence reproducibility. Our proposed two-tiered system of low vs nonlow grade, where the intermediate grade is grouped in the nonlow category has shown improved concordance.
Gastric neuroendocrine tumors (gNETs) are a rare entity that is increasing in incidence. Different pathophysiological processes can lead to the development of these tumors, appropriate histological analysis is necessary to differentiate between grade 1 (G1) and grade 2 (G2) tumors as this will impact the management of these patients based on their increased risk of lymph node and distant metastases. To provide a comprehensive clinicopathologic review of multifocal gastric neuroendocrine tumors, with particular emphasis on G1 and G2 tumors and differentiating between types I, II and II and risk stratification based upon immunohistochemical profile. This review is based on peer-reviewed literature and the authors’ experience. gNETs are a heterogenous group of tumors that is rising in incidence. These lesions while arise from the same cell type, they have different etiologies. Identifying the type of gNETs is a collective effort of clinical and pathologic correlation. The correct grading and staging of these lesions are of paramount significance, due its impact on patient management and prognosis.
Prolymphocytic transformation is a concept usually applied in the context of chronic lymphocytic leukemia/small lymphocytic lymphoma to describe the presence of a high percentage of prolymphocytes in peripheral blood (usually more than 55%). Prolymphocytic transformation has also been reported in mantle cell lymphoma (MCL) but only rarely in splenic marginal zone lymphoma (SMZL). We present two splenic B-cell lymphomas presenting in the leukemic phase and with increased prolymphocytes, both classified as SMZL with prolymphocytic transformation. One case clinically simulated B-prolymphocytic leukemia (B-PLL). Both lymphomas were very unusual because the tumor cells diffusely and strongly expressed cyclin D1 despite lacking the t(11; 14)(q13; q32) as detected by several approaches including next-generation sequencing, fluorescence in situ hybridization using CCND1 break apart probe and fusion probes for t(11; 14)(q13; q32), and conventional karyotyping. These cases therefore simulated prolymphocytic variants of MCL. The incidence of this phenomenon is unknown, and awareness of this potential alternate protein expression pattern is important in order to avoid diagnostic errors.
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