Female Adnexal Tumor of Probable Wolffian Origin (Wolffian Tumor): A Potential Mimic of Peritoneal Mesothelioma.

Wolffian tumor and its nosologic relative, the recently defined STK11 adnexal tumor are rare neoplasms thought to arise from mesonephric remnants. These tumors typically arise in the broad ligament, fallopian tube, and ovarian hilum and although most are associated with a good prognosis, up to 50% of STK11 adnexal tumors demonstrate aggressive clinical behavior. The chief differential diagnoses include endometrioid adenocarcinoma and sex cord stromal tumors. However, the morphologic and immunohistochemical features of these tumors exhibit considerable overlap with peritoneal mesothelioma. To fully characterize their immunophenotypic signature, we examined a total of 21 cases (18 Wolffian and 3 STK11 adnexal tumors) with standard markers used in the diagnosis of mesothelioma. Morphologic and immunohistochemical (IHC) features were reviewed and additional IHC performed for cases with available material. Patient age ranged from 25 to 73 (mean: 51) years. Sites included adnexa/broad ligament (6, 28%), paratubal (5, 24%), ovary/paraovarian (5, 24%), tubal (intraluminal) (2, 9.5%), pelvis (2, 9.5%), and liver (1, 5%). The mean tumor size was 9.3 cm (range: 0.2 to 22 cm). The histomorphology in most cases (14/21, 66%) consisted of tubular to solid sheets of neoplastic cells lined by columnar to cuboidal cells containing uniform round to oval nuclei. Compressed tubules with slit-like lumens and sieve-like pattern were also seen in at least 7 (33%) cases. Three cases demonstrated interanastomosing cords and trabeculae of epithelioid cells with cribriform and microacinar patterns growing within prominent myxoid stroma as described in STK11 adnexal tumors. In the cases with available IHC for 3 mesothelial markers (calretinin, WT1, D2-40), 55.5% (5 of 9) showed reactivity with all 3 markers. In cases with at least 2 available mesothelial markers, 69% (11/16) were positive for 2 markers (mostly calretinin and WT1). Claudin-4, MOC31, and BER-EP4 were negative in most cases tested (78% [7/9], 71.4% [5/7], and 100% [6/6], respectively). Given the resemblance to mesothelioma, there was initial strong consideration and/or actual misdiagnosis of mesothelioma in 3 cases (14%). In summary, the morphologic and immunohistochemical features of Wolffian tumor and its recently defined relative, STK11 adnexal tumor, can lead to misdiagnosis of mesothelioma, particularly when encountered in the disseminated or metastatic setting. Wolffian tumor and STK11 adnexal tumor should be considered in the differential diagnosis of all pelvic and peritoneal mesotheliomas.

Establishing vitreous glucose and beta-hydroxybutyrate thresholds to assist in the diagnosis of hypothermia.

The post-mortem diagnosis of hypothermia is challenging to establish due to the lack of pathognomonic findings and the confounding problem that any comorbidity may account for death. A 4-year retrospective case-control study was performed to compare the vitreous glucose and beta-hydroxybutyrate (BHB) concentrations between hypothermia deaths and controls. Over the study period 34 cases of hypothermia and 39 controls were analyzed. Hypothermia deaths versus controls had higher mean vitreous glucose (2.93 mmol/L vs. 1.14 mmol/L; p < 0.0001), BHB (1.89 mmol/L vs. 1.35 mmol/L; p = 0.01), and combined glucose+BHB (4.83 mmol/L vs. 2.46 mmol/L; p < 0.0001). Receiver operating characteristic (ROC) curves showed that the best model for predicting hypothermia in all cases was a combined vitreous glucose+BHB threshold of 2.03 mmol/L (sensitivity 88.2 %; specificity 56.4 %). A sub-group analysis broken down by detectable levels of blood ethanol showed that cases of hypothermia with and without ethanol maintained higher median vitreous glucose relative to the controls (2.05 vs. 0.35 mmol/L and 2.70 vs. 0.65 mmol/L; p = 0.02), however median BHB was only significantly elevated when ethanol was absent (1.88 vs. 1.42 mmol/L; p < 0.0001). Subsequent ROC curve analysis demonstrated that a better model for predicting hypothermia was in cases when blood ethanol was absent. In those deaths vitreous BHB alone had the best area under the curve, with an optimum threshold of 1.83 mmol/L (sensitivity 83.3 %; specificity 96.3 %). This study shows that post-mortem vitreous glucose and BHB are useful ancillary studies to assist in the diagnosis of hypothermia. Ethanol however is a confounder and can alter the utility of vitreous BHB when diagnosing hypothermia in those who have consumed alcohol prior to death.

Updates in Pathology for Retroperitoneal Soft Tissue Sarcoma.

Retroperitoneal tumors are extremely rare. More than 70% of primary retroperitoneal soft tissue tumors are malignant. The most common sarcomas in the retroperitoneum include liposarcomas and leiomyosarcoma, however other sarcomas, along with benign mesenchymal tumors, can occur. Sarcomas are a heterogenous group of tumors with overlapping microscopic features, posing a diagnostic challenge for the pathologist. Correct tumor classification has become important for prognostication and the evolving targeted therapies for sarcoma subtypes. In this review, the pathology of retroperitoneal soft tissue sarcomas is discussed, which is important to the surgical oncologist. In addition, less common sarcomas and benign mesenchymal tumors of the retroperitoneum, which may mimic sarcoma clinically and pathologically, are also discussed.

Single-Cell Analysis and Next-Generation Immuno-Sequencing Show That Multiple Clones Persist in Patients with Chronic Lymphocytic Leukemia.

The immunoglobulin heavy chain (IGH) gene rearrangement in chronic lymphocytic leukemia (CLL) provides a unique molecular signature; however, we demonstrate that 26/198 CLL patients (13%) had more than one IGH rearrangement, indicating the power of molecular technology over phenotypic analysis. Single-cell PCR analysis and next-generation immuno-sequencing identified IGH-defined clones. In 23% (18/79) of cases whose clones carried unmutated immunoglobulin heavy chain variable (IGHV) genes (U-CLL), IGH rearrangements were bialleic with one productive (P) and one non-productive (NP) allele. Two U-CLL were biclonal, each clone being monoallelic (P). In 119 IGHV-mutated (M-CLL) cases, one had biallelic rearrangements in their CLL (P/NP) and five had 2-4 distinct clones. Allelic exclusion was maintained in all B-clones analyzed. Based on single-cell PCR analysis, 5/11 partner clones (45%) reached levels of >5x10(9) cells/L, suggesting second CLL clones. Partner clones persisted over years. Conventional IGH characterization and next-generation sequencing of 13 CLL, 3 multiple myeloma, 2 Waldenstrom's macroglobulinemia and 3 age-matched healthy donors consistently identified the same rearranged IGH sequences. Most multiple clones occurred in M-CLL, perhaps indicative of weak clonal dominance, thereby associating with a good prognosis. In contrast, biallelic CLL occurred primarily in U-CLL thus being associated with poor prognosis. Extending beyond intra-clonal diversity, molecular analysis of clonal evolution and apparent subclones in CLL may also reflect inter-clonal diversity.