Citations

Neuroendocrine carcinomas of the breast are a rare subtype of invasive breast carcinomas, and those with morphologic and immunophenotypic features supporting Merkel cell carcinoma (MCC) are even more rare. Accurate diagnosis of these entities is important for clinical decision-making regarding the selection of optimal treatments. We report a patient withMCC in the deep breast parenchyma of a 52-year-old woman, without evidence of a cutaneous component. This tumor exhibited characteristic morphologic and immunophenotypic features of MCC, including sheets of high grade, hyperchromatic tumor cells, with perinuclear dot-like staining of keratin 20. To our knowledge, this is the sixth report of parenchymal breast MCC, and due to its rarity and aggressive course, we reviewed the literature, including prior experience on its diagnosis and management.

Abstract: Papillary eccrine adenoma/tubular apocrine adenoma (PEA/TAA) is a rare sweat gland neoplasm. Because PEA/TAA shares morphologic features with other sweat gland tumors, including digital papillary adenocarcinoma, histologic diagnosis may be challenging. We report a case of PEA/TAA presenting as a nodule on the left foot of a 43-year-old man. Histopathologic examination revealed a well-circumscribed dermal proliferation of variably sized glands composed of ductal cells with an outer layer of myoepithelial cells. By immunohistochemistry, the ductal tumor cells showed strong, diffuse expression of BRAF V600E, and the myoepithelial cells were positive for p63. This case illustrates the utility of immunohistochemistry in the diagnosis of this rare neoplasm. Particularly when PEA/TAA is located on an acral site, distinction from digital papillary adenocarcinoma is critical, because these tumors show significant differences in clinical behavior.

ABSTRACTVarious cutaneous adnexal neoplasms have been associated with gene fusions as the main driver of their histogenesis, most of which showed poroid or hidradenomatous differentiation or represented other tumors of sweat glands. Recently, we encountered two cases of primitive basaloid neoplasms of predominantly folliculogenic/pilosebaceous origin, both surprisingly harboring recurrent EWSR1 rearrangements. Both tumors presented in young patients of either sex (1 F; 17 years; 1 M; 37 years) and involved the dermis and subcutaneous tissue of the abdominal wall (case 1) and the buttock (case 2). Histologically, the tumors were composed of primitive, basaloid cells with areas of keratinization (case 1) or foci of sebaceous differentiation (case 2) and stained strongly with keratins, p40 (case 1) or p63 (case 2), while lacking significant CD99 expression in both cases. Case 1 harbored an EWSR1::FLI1 fusion while case 2 harbored an EWSR1::PBX3 fusion. Clinical follow‐up was available for case 2 and showed no evidence of disease at 15 months of follow‐up. Methylation profiling showed case 1 to cluster with cutaneous squamous cell carcinoma, while case 2 was independent but positioned close to salivary gland epithelial‐myoepithelial carcinoma. These findings expand on the histopathologic and molecular genetic features of basaloid tumors with apparent adnexal differentiation and raise awareness to carefully interpret and correlate molecular findings with morphology and immunophenotype to avoid misinterpretation as a mesenchymal neoplasm.

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 Multiplexed Immunofluorescence (MxIF) enables detailed immune cell phenotyping, providing critical insights into cell behavior within the tumor immune microenvironment (TIME). However, signal integrity can be compromised due to the complex cyclic staining processes inherent to MxIF. Hematoxylin and Eosin (H&E) staining, on the other hand, offers complementary information through its depiction of cell morphology and texture patterns and is often visually cross-referenced with MxIF in clinical settings. In this study, we proposed a novel framework to align H&E and MxIF images for precise cross-modal cell feature validation. Using cell detection outputs from each modality as anchors, we formulated the multimodal image registration problem as point set alignment. Coherent Point Drift (CPD) is employed for initial alignment, followed by Graph Matching (GM) for refinement. Evaluations on ovarian cancer tissue microarrays (TMAs) demonstrate that our method achieves high alignment accuracy, enabling reliable validation of cell-level features across modalities for both restained and serial sections. Our results indicate that restained H&E enhances confidence in findings derived from MxIF. Additionally, we demonstrated the feasibility of generating high-quality virtual H&E images from MxIF data when restained H&E is unavailable, offering a viable alternative for integrated multimodal analysis.

A subset of desmoplastic melanomas (DMs) can show extensive morphologic and immunohistochemical overlap with cutaneous diffuse-type neurofibroma. Neurofibroma-like desmoplastic melanoma (NFLDM) thus poses a significant diagnostic pitfall because the clinical implications of these 2 entities differ dramatically. A series of 17 DMs, including 5 cases of NFLDM, were compared with a cohort of 53 cutaneous diffuse-type neurofibromas to explore the utility of molecular testing in the differential diagnosis between NFLDM and neurofibroma and to determine potentially useful morphologic features in this differential diagnosis. Unlike NFLDM, cutaneous diffuse-type neurofibromas: (1) rarely feature intratumoral or peritumoral lymphoid aggregates, (2) consistently harbor an intrinsic stromal support vasculature composed of evenly spaced capillary-sized vessels, and (3) infiltrate adjacent adipose tissue in a dermatofibrosarcoma protuberans–like manner with a complete lack of chronic inflammation or fat necrosis at the leading edge of the tumor. Conversely, DMs, including NFLDM: (1) do not contain Wagner-Meissner bodies, (2) often induce fat necrosis and/or chronic inflammation at the interface with adjacent fibroadipose tissue, (3) lack the intrinsic capillary-sized stromal vasculature observed in most neurofibromas, and (4) may harbor foci of perineuriomatous differentiation, mimicking a hybrid nerve sheath tumor. Any deviation from the expected clinical or morphologic features of cutaneous diffuse-type neurofibroma should raise suspicion for NFLDM. Although not entirely sensitive or specific, molecular testing can help to support the diagnosis of NFLDM by demonstrating genetic abnormalities associated with melanoma, including a UV-light–induced mutational signature, high tumor mutational burden, and/or chromosomal copy number alterations typical of melanoma.