Tekin, Burak

Abstract Objectives Sarcomatoid urothelial carcinoma (sUC) is associated with poor clinical outcomes. Herein, we evaluated clinicopathologic features (including PD-L1 expression) for institutional cases. Methods Sixty-five patients with sUC treated by radical cystectomy were matched for age, sex, and pathologic stage to 190 patients with pure urothelial carcinoma (UC). Outcomes were evaluated using the Kaplan-Meier method. Immunohistochemistry (IHC) results for tumor-specific PD-L1 expression in sUC were quantified using H-scores (range, 0-300). Cases with constitutive PD-L1 expression (cPD-L1; H-score ≥240) were evaluated for amplification events using fluorescence in situ hybridization (n = 28), mate-pair sequencing (Mpseq; n = 6), RNA sequencing (n = 5), and targeted next-generation sequencing (n = 8). PD-L1 regulatory pathways were evaluated using gene set enrichment analysis in the Cancer Hallmark dataset. Results Most patients with sUC had advanced disease (≥pT2, 62/65, 95%), without significant differences in overall and cancer-specific survival, when matched to pure UC. Median PD-L1 H-scores using different clones were 100 (SP142), 120 (SP263), and 195 (22C3). cPD-L1 was seen in 43% (28/65) of cases of sUC that were enriched for TP53, TERT, and CDKN2A/B alterations. PD-L1 amplification was identified in 7 (of 28, 25%) of these cases. Bionformatics analysis consistently identified IL6-JAK-STAT3 and interferon α/γ signaling in sUC with cPD-L1 expression. Conclusions Our results suggest that cPD-L1 expression in most sUC occurs secondary to IL6-JAK-STAT3 and interferon α/γ signaling. This provides a biologic rationale for evaluating response to immunotherapy in this patient population.

Abstract: Melanoma exhibits a broad spectrum of histopathologic variations, including rare forms with neural differentiation. Neurotropism in melanoma encompasses both perineural invasion and neural-like transformation, but the prognostic implications of these features remain uncertain. Although (peri)neural invasion is well documented, true neural differentiation in melanomas is exceedingly rare. In this study, we describe an unusual case of primary cutaneous malignant melanoma exhibiting extensive Wagner–Meissner-like bodies, a feature more commonly associated with benign neural tumors and nevi. In this case, histopathology revealed a dual-component lesion with a neurotized and an epithelioid melanocytic component, both showing PRAME expression and p16 loss. Chromosomal microarray identified heterozygous loss of 9p22.1p13.1 (including CDKN2A / CDKN2B ), and loss of 10q22.2q26.3 (including PTEN ), supporting malignancy. These findings suggest that in this case, Wagner–Meissner-like bodies likely represent neurotization rather than a benign or collision lesion, highlighting the need for integrated histopathologic, immunohistochemical, and molecular analysis in challenging melanocytic neoplasms.

We performed a retrospective review of patients with lichen planus pemphigoides (LPP) over almost a 23-year period to gather clinical, histopathological, immunological and treatment-related information and to compare idiopathic LPP with drug-induced LPP. This study represents the largest single-institution case series of LPP to date and includes novel findings related to mucosal involvement, autoantibody profiles and the value of monitoring bullous pemphigoid (BP) autoantibodies in predicting treatment response. This study also includes characteristic histopathological findings that can aid in the diagnosis and differentiation of LPP from BP, in addition to comparisons between idiopathic LPP and drug-induced LPP.

Abstract Objectives We aimed to assess the expression of biomarkers of response to antibody-drug conjugates (TROP2 and nectin-4) and immune microenvironment (NKG7, PD-L1, and B7-H3) in penile squamous cell carcinoma (pSCC). Methods Our archive was queried for patients who had a penectomy for pSCC between 2000 and 2022. Primary tumors were immunostained for B7-H3 and NKG7, while metastatic specimens were immunostained for TROP2 and nectin-4. Expression of PD-L1, TROP2, and nectin-4 in primary tumors was previously characterized. H-scores (0-300) were used to quantify expression. Associations between biomarkers, tumor-infiltrating lymphocytes (TILs), and clinicopathologic and outcome parameters were evaluated. Results For both TROP2 and nectin-4, H-scores within the lymph node metastases were higher compared to those within the primary tumors (mean, 264.5 vs 244.8, P = .0003; mean, 170.6 vs 146.7, P = .05, respectively; 33 paired specimens). For B7-H3 (n = 107), 32.7% of the primary tumors had an H-score of more than 0. In 34.8% of the cases, NKG7 expression was observed in 25% to 50% of the TILs. A significant association was noted between TIL density, B7-H3, NKG7, and PD-L1 expression. Conclusions Therapeutic strategies targeting TROP2 and nectin-4 hold promise for patients with advanced pSCC. The potential of PD-L1, B7-H3, and NKG7 for predicting response to immunomodulatory treatment warrants further research.

Abstract: There is a paucity of data regarding porokeratosis confined to the penis and scrotum. We evaluated our single-institutional experience regarding this entity. We interrogated our pathology archive for all specimens from the penis or scrotum, signed out as porokeratosis between 2000 and 2022. Clinical and histopathological features were reviewed, including the number of cornoid lamella(e) per tissue profile and squamous dysplasia. Nine patients were included in the study. The median age at the time of diagnosis was 51 years. Multiple lesions were present in 3 patients. Six patients had exclusively penile involvement, whereas 2 patients had exclusively scrotal involvement. One patient had multiple lesions consistent with porokeratosis ptychotropica, extending from the scrotum to the buttocks and perineum. Clinically, a collarette of scale was noted in 3 patients and diagnosis of porokeratosis was considered in 1 patient before biopsy. Histopathologically, 2 patients exhibited multiple cornoid lamellae in the same profile and 1 patient had follicular cornoid lamellae. Focal squamous dysplasia was only present in 1 patient. Follow-up was available for 5 patients (median duration: 35 months). In 4 patients, the lesions were removed completely during the shave biopsy procedure. At the past follow-up, there were no signs of recurrence or malignant transformation to squamous cell carcinoma in any patient. Porokeratosis involving the penis and/or scrotum may be elusive to diagnosis based on clinical features alone, emphasizing the role of histopathological examination. Increased awareness of this entity may help better delineate its clinicopathological presentation and appropriate classification.