The American Journal of Surgical Pathology最新文献

Sex cord-stromal tumors (SCSTs) account for the second most common category of testicular neoplasms and include several entities that may show overlapping morphologies and present diagnostic challenges. We analyzed a cohort of 120 testicular SCSTs and investigated the diagnostic utility of SRY-box transcription factor 9 (SOX9), forkhead box protein L2 (FOXL2), and steroidogenic factor 1 (SF-1) immunohistochemical stains. The results were compared with the more commonly used SCST markers, inhibin α, calretinin, and Wilms' tumor 1 (WT1). SF-1 was overall the most sensitive stain (91%), followed by inhibin α (70%), calretinin (52%), FOXL2 (50%), SOX9 (47%), and WT1 (37%), but sensitivities varied by tumor type. SOX9 and calretinin were more commonly positive in sex cord elements versus stromal elements (62% vs. 27% and 47% vs. 9%, respectively), whereas FOXL2 was more commonly positive in stromal elements versus sex cord elements (100% vs. 55%) when excluding Leydig cell tumors from the stromal category. Although no individual stain was diagnostically specific, some immunophenotypic patterns were noted that may help in the subclassification of SCSTs. We conclude that SOX9, FOXL2, and SF-1 are useful immunohistochemical stains for confirming sex cord-stromal differentiation in testicular tumors and provide increased sensitivity as well as additional diagnostic information, especially when combined with the more commonly used inhibin α, calretinin, and WT1 immunostains. Although morphology is paramount for subclassification of SCSTs, knowledge of certain immunohistochemical patterns may be helpful for diagnostically challenging cases.

The Lower Anogenital Squamous Terminology (LAST) Project recommends the use of p16 immunohistochemistry as an adjunct to morphologic assessment of cervical biopsies according to a specific set of criteria. We analyzed the effect of adjunctive p16 according to LAST criteria in a US-based diagnostic utility study involving 70 surgical pathologists providing a total of 38,500 reads on cervical biopsies. Compared with the results obtained using hematoxylin and eosin-stained slides only, including p16-stained slides per LAST criteria increased sensitivity and specificity for diagnosing histologic high-grade squamous intraepithelial lesions across all cases by 8.1% (95% confidence interval [95% CI], 6.5-9.7; P<0.0001) and 3.5% (95% CI, 2.8-4.2; P<0.0001), respectively, using expert consensus diagnoses on hematoxylin and eosin+p16 as reference. Within the subset of cases classified by the pathologists as fulfilling the LAST criteria, adding p16 significantly increased both sensitivity (+11.8%; 95% CI, 9.5-14.0; P<0.0001) and specificity (+9.7%; 95% CI, 7.8-11.5; P<0.0001). However, a comparable improvement in sensitivity (+11.0%; 95% CI, 7.8-14.1; P<0.0001) was found when p16 was used in cases for which p16 staining was not ordered per LAST by the pathologists, whereas specificity decreased by -0.8% (95% CI, -1.1 to -0.5; P<0.0001). The study demonstrates a clinically and statistically significant increase in sensitivity and specificity for high-grade squamous intraepithelial lesion when p16 is used according to LAST criteria. Expanding the use of p16 into non-LAST cases would lead to a comparable improvement in sensitivity within this subgroup of biopsies, at the cost of a minimal, but statistically significant difference in specificity.

The molecular characteristics of lymphoepithelioma-like intrahepatic cholangiocarcinoma (LELCC) remain elusive. We examined 27 LELCC cases through next-generation sequencing using a panel of genes commonly mutated in primary liver cancers. Alterations in BAP1, ARID1A, ARID2, and PBRM1 were detected through immunohistochemistry. Fluorescence in situ hybridization was performed to analyze FGFR2 fusions and CCND1 amplification. LELCC is histologically classified as predominantly undifferentiated or glandular. Epstein-Barr virus-encoded small RNA (EBER) expression was found in 16 LELCCs. Approximately 50% of LELCCs expressed programmed death-ligand 1 strongly. Notably, recurrent pTERT and TP53 mutations were detected in 9 (38%) and 8 (33%) tumors, respectively. Only 2 LELCCs exhibited loss of expression for PBRM1. Alterations in genes typically involved in intrahepatic cholangiocarcinoma, including IDH1, IDH2, ARID1A, ARID2, and BAP1, and FGFR2 fusions, were not identified. The 2-step clustering analysis showed 2 distinct subgroups in LELCC, which were separated by EBER expression. A meta-analysis of all reported cases (n=85) has shown that EBER+ LELCC is strongly associated with the female sex, younger age, and exhibited predominantly glandular differentiation (P=0.001, 0.012, and <0.001, respectively). Patients with EBER- LELCC were more likely to have viral hepatitis and cirrhosis (P=0.003 and 0.005, respectively). Genetic analysis demonstrated that EBER- LELCC was significantly associated with pTERT and TP53 mutations (P=0.033 and 0.008, respectively). In conclusion, LELCC is genetically distinct from intrahepatic cholangiocarcinoma. EBER- LELCC may exhibit a different pathogenesis from EBER+ LELCC. High programmed death-ligand 1 expression in LELCC has implications for potential immunotherapeutic strategies.

Inflammatory pseudotumor is a term used to designate inflammation-rich tumefactive lesions. Following the exclusion of specific entities such as IgG4-related disease and other neoplastic entities previously included in this entity, the majority of hepatic pseudotumors show a prominent fibrohistiocytic inflammatory reaction and have been previously categorized as fibrohistiocytic variant of hepatic pseudotumor (FHVHPT). The goal of this study was to examine the clinical, radiologic, histologic, and etiologic aspects of this entity. After excluding neoplastic diseases, we identified 30 patients with FHVHPT from 3 institutions between 2009 and 2019. We extracted demographic and clinical data, liver function tests as well as culture results and radiologic information. Hematoxylin and eosin-stained slides were reviewed for pattern of inflammation as well as its cellular composition. Immunohistochemistry for IgG4 and IgG was performed in all cases. The mean age of the 30 lesions characterized as FHVHPT was 56 years (range: 23 to 79 y). Nineteen patients showed solitary lesions; 11 were multiple. The mean size of the lesion was 3.8 cm (range: 1 to 7.5 cm). On imaging, a neoplastic process or metastasis was the leading diagnostic consideration (n=15, 50%). The most common symptom was abdominal pain (n=14/30); 8 patients presented with symptoms compatible with an infectious process, including fever. The inflammatory infiltrate was dominated by lymphocytes and plasma cells, and in most cases, a prominent histiocytic infiltrate (22/30). Neutrophils were identified in 12 cases, with microabscess noted in 8. Storiform pattern of fibrosis was seen in 14/30 cases; obliterative phlebitis was not identified. Culture identified a microorganism in 4 of 9 cases evaluated. The mean IgG4 count was 9.3 per HPF (range: 0 to 51) with 9 of the 26 (35%) biopsies showing >10 IgG4 positive plasma cells per HPF. The mean IgG4 to IgG ratio was 8% (range: 8% to 46%). A hepatectomy was performed in 4 cases. On broad spectrum antibiotics (n=14) the lesions either resolved or decreased in size. Eight patients did not receive specific therapy, nevertheless, the lesion(s) resolved spontaneously in 6 cases, remained stable or decreased in size in 2 cases. Notably, none of these patients showed evidence of a hepatic recurrence. FHVHPT, a tumefactive lesion that mimics hepatic neoplasia, is histologically characterized by a fibrohistiocytic infiltrate. In the majority of patients FHVHPT represents the organizing phase of hepatic abscess and can be successfully managed with antibiotic therapy.

Mucin-producing salivary adenocarcinomas were historically divided into separate colloid carcinoma, papillary cystadenocarcinoma, and signet ring cell carcinoma diagnoses based on histologic pattern, but have recently been grouped together in the adenocarcinoma not otherwise specified category. It is currently unclear if these tumors represent 1 or more distinct entities and how they are related to well-circumscribed papillary mucinous lesions with recurrent AKT1 E17K mutations that were recently described as salivary intraductal papillary mucinous neoplasm. Here, we sought to evaluate the clinicopathologic and molecular features of salivary mucinous adenocarcinomas to clarify their classification. We identified 17 invasive mucin-producing salivary adenocarcinomas, 10 with a single histologic pattern, and 7 with mixed patterns. While most tumors demonstrated papillary growth (n=15), it was frequently intermixed with colloid (n=6) and signet ring (n=3) architecture with obvious transitions between patterns. All were cytokeratin 7 positive (100%) and cytokeratin 20 negative (0%). Next-generation sequencing performed on a subset demonstrated recurrent AKT1 E17K mutations in 8 cases (100%) and TP53 alterations in 7 cases (88%). Of 12 cases with clinical follow-up (median: 17 mo), 4 developed cervical lymph node metastases, all of which had colloid or signet ring components. Overall, overlapping histologic and immunohistochemical features coupled with recurrent AKT1 E17K mutations across patterns suggests that mucin-producing salivary adenocarcinomas represent a histologically diverse single entity that is closely related to tumors described as salivary intraductal papillary mucinous neoplasm. We propose a unified mucinous adenocarcinoma category subdivided into papillary, colloid, signet ring, and mixed subtypes to facilitate better recognition and classification of these tumors.