Immunoglobulin light chain transcript detection by ultrasensitive RNA in situ hybridization for B-cell lymphoma diagnosis.

Evaluation of B-cell clonality can be challenging in the interpretation of lymphoid infiltrates on tissue sections. Clonality testing based on IG gene rearrangements analysis by PCR (IG-PCR) is the gold standard. Alternatively, B-cell clonality can be assessed by the recognition of immunoglobulin light chain (IgLC) restriction, by immunohistochemistry (IHC), chromogenic in situ hybridization (ISH) or flow cytometry (FC). IG-PCR requires molecular facilities, and FC requires cell suspensions, both not widely available in routine pathology units. This study evaluates the performance of B-cell clonality detection by IgLC-RNAscope® (RNAsc) in a group of 216 formalin-fixed, paraffin-embedded samples including 185 non-Hodgkin B-cell lymphomas, 11 Hodgkin lymphomas (HL) and 20 reactive samples. IgLC-RNAsc, performed in parallel with FC in 53 cases, demonstrated better performances (93% vs 83%), particularly in diffuse large B-cell lymphoma (98% vs 71%) and follicular lymphoma (93% vs 83%) diagnosis. IgLC-RNAsc was also superior to IHC and ISH especially in samples with limited tumor cell content, where IG-PCR was not informative. Performed for the first time on mediastinal lymphomas, IgLC-RNAsc identified monotypic IgLC transcripts in 69% of primary mediastinal large B-cell lymphoma (PMBCL) and 67% of mediastinal gray zone lymphomas (MGZL). IGK/L double-negative cells were detected in 1 PMBCL, 2 MGZL, and all classical HL, while monotypic IgLC expression appeared to be a hallmark in nodular lymphocyte-predominant HL. IgLC-RNAsc demonstrates to be a powerful tool in B-cell lymphoma diagnosis, above all in challenging cases with limited tumor cell content, ensuring in situ investigations on mechanisms of Ig regulation across lymphoma entities.

Cutaneous Syncytial Myoepithelioma with Positive CD34 Immunohistochemical Staining: An Unusual Tumor and a Challenging Diagnosis.

Cutaneous syncytial myoepithelioma (CSM) is a rare type of cutaneous neoplasm that typically presents as a solitary and well-circumscribed nodule on the skin. It predominantly occurs on the upper and lower extremities of adult patients. Immunohistochemically, CSM is characterized by the co-expression of smooth muscle and epithelial markers. Fluorescence in situ hybridization (FISH) targeting the EWSR1 gene rearrangement is an important diagnostic tool for CSM. In our case report, we found the focal positivity for CD34, which has never been previously observed; this was mostly confined to a central area of the neoplasm.

Integrated Biomarker Analysis Reveals L1CAM as a Potential Stratification Marker for No Specific Molecular Profile High-Risk Endometrial Carcinoma.

Histopathologic assessment of high-risk endometrial cancer (EC) suffers from intersubject variability and poor reproducibility. The pragmatic classification in four molecular subgroups helps to overcome these limits, showing a significant prognostic value. The "no specific molecular profile" (NSMP) is the most heterogeneous EC subgroup, requiring further characterization to better guide its clinical management. DNA sequencing of POLE exonuclease domain and immunohistochemistry for PMS2, MSH6, and p53 were performed in order to stratify a cohort of 94 high-risk EC patients in the four molecular subgroups. Moreover, a panel of seven additional biomarkers was tested. Patients were found to be 16% POLE-mutated, 36% mismatch repair-deficient, 27% p53-abnormal, and 21% NSMP. In the multivariable model, molecular groups confirmed their significant association with disease-specific survival and progression-free survival, with p53-abnormal and NSMP endometrial cancer characterized by poor outcomes. Among the additional evaluated biomarkers, L1CAM was the only one with a significant prognostic value within the NSMP subgroup. NSMP/L1CAM-positive patients experienced the worst outcome and were "early-relapsing" after platinum-based chemotherapy, with a significantly shorter platinum-free interval compared to L1CAM-negative patients. L1CAM appears to be a promising candidate as a prognostic and predictive biomarker in the high-risk NSMP subgroup, which is actually known to lack specific molecular markers.

Risk Assessment in Solitary Fibrous Tumor of the Uterine Corpus: Report of a Case and Systematic Review of the Literature.

Solitary fibrous tumor (SFT) is an uncommon fibroblastic tumor occurring preferentially in the pleura, with a variable clinical course. SFT can arise also in numerous extrathoracic sites and very rarely in the female genital tract, with only scarce reports of uterine SFT. We reported a new uterine SFT arising in a 45-year-old woman, and we performed a systematic review of SFT cases of the uterine corpus interrogating the electronic databases PubMed, Web of Science, and Scopus. We identified only 13 patients diagnosed with SFT of the uterine corpus, including our one. Complete clinical workout at disease presentation showed no evidence of extrauterine spread in all cases, except for 1 patient who presented with metastatic disease. Tumor recurrences/metastases occurred in a minority of the patients and were poorly related to clinicopathological risk factors and patients stratification based on different scoring systems. Since the long-term clinical behavior of uterine SFT is limited and poorly predictable, extended follow-up is recommended also for all cases arising in the uterine corpus.