Long-Term Survival and Biomarker Analysis Evaluating Neoadjuvant Plus Adjuvant Relatlimab (anti-LAG3) and Nivolumab (anti-PD1) in Patients With Resectable Melanoma.

Immune checkpoint blockade (ICB) has revolutionized outcomes for patients with melanoma across multiple disease settings. In patients with advanced, unresectable disease, the ICB combination of nivolumab (anti-PD1) and relatlimab (anti-LAG-3) has demonstrated improved clinical outcomes compared with nivolumab monotherapy. There exists an unmet need to identify biomarkers that predict response to this combination regimen and rational therapeutic strategies to overcome resistance.

Subcutaneous Panniculitis-Like T-Cell Lymphoma With Increased γδ T Cells: A Potential Diagnostic Pitfall.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare primary cutaneous T-cell lymphoma with adipotropism characterized by infiltration of CD8 + T cells exhibiting a cytotoxic and αβ phenotype. Although SPTCL is typically indolent, distinguishing it from more aggressive cutaneous lymphomas such as primary cutaneous γδ T-cell lymphoma is critical for accurate prognosis. We present a case of SPTCL in a 26-year-old Asian woman with a history of hemophagocytic lymphohistiocytosis, who presented with nonulcerated, erythematous patches and hyperpigmented nodules on her extremities and trunk persisting for 5 months.

TROP2 is highly expressed in cutaneous squamous cell carcinomas and a subset of adnexal carcinomas: A potential therapeutic target with TROP2-directed antibody drug conjugates.

Trophoblast cell surface antigen 2 (TROP2) has emerged as a promising therapeutic target in oncology. TROP2-directed antibody-drug conjugates (ADCs) are now approved for treating advanced malignancies such as breast carcinomas by the Food and Drug Administration. However, the expression patterns and potential therapeutic relevance of TROP2 in cutaneous neoplasms remain largely unexplored.

INSM1: A highly sensitive marker for primary and metastatic Merkel cell carcinoma, superior to SOX11, pancytokeratin, and CK20.

Detection of Merkel cell carcinoma (MCC) micrometastases in sentinel lymph nodes (SLNs) often necessitates immunohistochemical studies like pancytokeratin (panCK) or CK20. However, panCK can label non-epithelial cells, particularly dendritic reticulum cells, complicating interpretation, while CK20 is absent in up to 24 % of MCCs, leading to potential false negatives. Recent evidence suggests SOX11 and INSM1 as sensitive nuclear neuroendocrine markers, though their comparative performance in this setting remains unclear.

Primary Cutaneous Anaplastic Large Cell Lymphoma With TCR-γδ Expression: A Case Series of Eleven Patients of a Rare Immunophenotypic Variant.

Background: Primary cutaneous anaplastic large cell lymphoma (pcALCL) and lymphomatoid papulosis (LyP) are indolent CD30-positive lymphoproliferative disorders that rarely express TCR-γδ. However, primary cutaneous gamma-delta T-cell lymphoma (pcGDTCL), characterized by TCR-γδ expression on neoplastic cells, is a rare, aggressive cutaneous T-cell lymphoma with a poor prognosis. Accurate differentiation is essential due to distinct clinical behavior and treatment.

Melanoma With RNF11::BRAF Fusion: A Novel Fusion Previously Undescribed in Melanoma.

B-Raf Proto-Oncogene ( BRAF ) fusions are rare in melanomas. We present a case of cutaneous melanoma with a Ring Finger Protein 11 ( RNF11 ) ::BRAF fusion in a 63-year-old man with a history of stage IB melanoma on the right upper back (pT2apN0cM0; nonulcerated with a Breslow thickness of 1.2 mm).

Genomic and Transcriptomic Profiling of Digital Papillary Adenocarcinomas Reveals Alterations in Matrix Remodeling and Metabolic Genes.

Background: Digital papillary adenocarcinoma (DPAC) is a rare but aggressive cutaneous malignant sweat gland neoplasm that occurs on acral sites. Despite its clinical significance, the cellular and genetic characteristics of DPAC remain incompletely understood.

Methods: We conducted a comprehensive genomic and transcriptomic analysis of DPAC (n = 14) using targeted next-generation DNA and RNA sequencing, along with gene expression profiling employing the Nanostring Technologies nCounter IO 360 Panel.

Complete Response to Immunotherapy Using Pembrolizumab in a Patient With Conjunctival Squamous Cell Carcinoma With Nodal Metastasis.

A 92-year-old woman presented with a large bulbar conjunctival mass in the OD. She also had a palpable parotid mass which on fine needle aspiration biopsy confirmed to be metastatic squamous cell carcinoma. The conjunctival mass was biopsied to confirm the diagnosis of squamous cell carcinoma with positive programmed cell death ligand 1 expression and a high tumor mutation burden.

TRPS1 expression in non-melanocytic cutaneous neoplasms: an immunohistochemical analysis of 200 cases.

Background: Although trichorhinophalangeal syndrome type 1 (TRPS1) was initially thought to be highly sensitive and specific for carcinomas and mesenchymal tumors of mammary origin, more recent data suggest its expression is not limited to breast neoplasms but also can be seen in other cutaneous neoplasms, such as extramammary Paget disease and squamous cell carcinoma (SCC) in situ.

Methods: Two-hundred cases of non-melanocytic cutaneous neoplasm, including basal cell carcinomas (BCCs) (n = 41), SCCs (n = 35), Merkel cell carcinomas (MCCs) (n = 25), and adnexal neoplasms (n = 99), were tested for TRPS1 expression using a monoclonal anti- TRPS1 rabbit anti-human antibody.

Results: TRPS1 expression was present in almost all cases of SCC (94%), with a median H-score of 200, while it was either absent or only focally present in most BCCs (90%), with a median H-score of 5.

TRPS1 expression in primary and secondary extramammary Paget diseases: An immunohistochemical analysis of 93 cases.

Extramammary Paget disease (EMPD) predominantly manifests de novo as primary EMPD, with less than 30 % of cases associated with underlying internal malignancy (secondary EMPD). Differentiating primary from secondary EMPDs based solely on histopathology poses challenges, often necessitating supplementary screening, such as endoscopy or imaging studies, to definitively exclude underlying carcinomas like colonic adenocarcinoma. Recently, TRPS1 immunohistochemistry, initially identified as a sensitive and specific marker for carcinomas and mesenchymal tumors of mammary origin, has been proposed for EMPD.

PRAME and LEF1 in Combined Deep Penetrating Nevus and Combined Blue Nevus: Utility and Pitfalls.

Deep penetrating nevi (DPN), particularly those showing combined features, or combined deep penetrating nevi (CDPN), may show histopathological resemblance to blue nevus (BN) and melanoma. Preferentially Expressed Antigen in MElanoma (PRAME) is a marker that helps distinguish melanoma from benign melanocytic lesions. Lymphoid enhancer-binding factor 1 (LEF1) has been proposed to be used in conjunction with β-catenin for diagnosis of DPN.

Telomerase reverse transcriptase immunohistochemical expression is sensitive but not specific for TERT gene amplification in acral melanoma.

Background: TERT gene amplification (TGA) is a mechanism of telomerase reverse transcriptase (TERT) upregulation frequently utilized by acral melanomas (AMs). Currently, the utility of TERT immunohistochemistry (IHC) to predict TGA status in AMs is poorly documented.

Methods: AMs (26 primary and 3 metastatic) and non-acral cutaneous melanomas (6 primary) were subjected to immunohistochemical analysis using anti-TERT antibody to demonstrate protein expression and fluorescence in situ hybridization (FISH) to assess genomic copy number alteration.

Lymphomatoid papulosis with DUSP22-IRF4 rearrangement: A case report and literature review.

Lymphomatoid papulosis (LyP) with DUSP22-IRF4 rearrangement is a rare, recently described variant of LyP histopathologically characterized by a biphasic growth pattern, with epidermotropic small-to-medium-sized atypical T-cells and dermal large and transformed T-cells diffusely expressing CD30. LyP with DUSP22-IRF4 rearrangement can mimic other cutaneous lymphoproliferative disorders, particularly primary cutaneous anaplastic large cell lymphoma (PCALCL) or transformed mycosis fungoides (MF). Unlike PCALCL or transformed MF, LyP with DUSP22-IRF4 rearrangement shows an indolent clinical behavior, with frequent spontaneous regression of untreated lesions.

Immunohistochemical expression of TRPS1 in mammary Paget disease, extramammary Paget disease, and their close histopathologic mimics.

Background: Trichorhinophalangeal syndrome type 1 (TPRS1) expression has been found to be highly sensitive and specific for breast carcinomas. The frequency of TRPS1 expression in cutaneous neoplasms such as mammary Paget disease (MPD) and extramammary PD (EMPD) is currently unknown. We assessed the utility of TRPS1 immunohistochemistry (IHC) in the evaluation of MPD, EMPD, and their histopathologic mimics, squamous cell carcinoma in situ (SCCIS) and melanoma in situ (MIS).