Journal of Cutaneous Pathology最新文献

Special site pigmented lesions often present a diagnostic challenge for clinicians and for pathologists. Lesions of the genital region present even further challenges due to the sensitivity of the anatomic location and preference to defer physical exam and biopsy. Even after biopsy, the diagnostic challenge persists owing to the frequent presence of atypical features in these sites and the technical difficulties associated with performing complete excisions. Immunohistochemistry plays a crucial role in the classification and categorization of these lesions. PRAME (PReferentially expressed Antigen in MElanoma) is a nuclear receptor and transcriptional regulator that regulates cell differentiation, growth, and apoptosis. Immunohistochemistry for PRAME has proven valuable in assisting pathologists to classify various cutaneous melanocytic proliferations all over the human body. Our study sought to investigate the use of PRAME in determining the biologic nature of pigmented lesions of the genital region. A search of medical records identified 53 cases of genital pigmented lesions for review. Each case received MART1 and PRAME IHC for evaluation and classification by two board certified dermatopathologists. The results found that PRAME was negative (zero nuclear staining) in a total of 32 benign lesions (i.e., melanosis including macules and lentigos as well as nevi). One dysplastic nevus showed focal weak PRAME expression in less than 10% of lesional melanocytes. PRAME was overwhelmingly positive (4+ staining, > 75% of nuclei) in 90% of the malignant lesions (i.e., invasive melanoma and melanoma in situ). Overall, we conclude that PRAME remains a valuable tool in the diagnostic workup of diagnosing pigmented lesions of the genital region.

Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1), programmed cell death ligand 1 (PD-L1), and cytotoxic lymphocyte-associated antigen-4 (CTLA-4) have revolutionized cancer treatment but are associated with immune-related adverse events, particularly cutaneous toxicities. We report a rare case of pembrolizumab-exacerbated pigmented purpuric dermatosis (PPD) in a 77-year-old male with a history of metastatic non-small cell lung cancer. His rash, initially confined to the lower extremities, worsened and became widespread to involve the trunk after pembrolizumab initiation. Histopathology showed perivascular lymphocytic infiltrate with extravasated erythrocytes without vasculitis, compatible with PPD; however, due to some lymphocyte atypia and exocytosis, together with the clinically widespread lesions, there was initial concern for PPD-like mycosis fungoides (MF). Subsequent T-cell receptor gene rearrangement studies revealed no monoclonal lymphoid population, and the later resolution of the rash with treatments typical for PPD did not support MF. This represents only the second reported case of ICI-associated PPD and highlights a potential diagnostic pitfall with histopathology and clinical presentation mimicking PPD-like MF. Our case contributes to the expanding spectrum of ICI-related cutaneous reactions and underscores the importance of recognizing inflammatory dermatoses with atypical histopathologic features for dermatologists and dermatopathologists.

A 74-year-old female presented with a progressively enlarging and intermittently tender hyperpigmented lesion beneath her left rib cage. Physical examination revealed a firm, telangiectatic linear plaque clinically suspected to represent a hypertrophic scar. A shave biopsy was performed. Histologic sections demonstrated a dermal proliferation of plump spindled cells without cytologic atypia, organized in short fascicles interspersed with hyalinized collagen bundles. Immunohistochemical stains revealed CD34, desmin, and smooth muscle actin expression in the lesional cells. SOX10, S100, and Melan-A were negative. Retinoblastoma 1 (Rb) staining demonstrated loss of nuclear expression in the spindle-shaped cells. The findings support a diagnosis of myofibroblastoma, which rarely occurs in the skin. Myofibroblastoma is an uncommon benign mesenchymal neoplasm composed of fibroblasts and myofibroblasts with recurrent monoallelic loss of the 13q14 region, where RB1 resides, with resultant loss of Rb expression. Although the differential diagnosis was vast, this case highlights the utility of Rb immunohistochemistry in the diagnosis of cutaneous myofibroblastoma.

BAP1-inactivated melanocytic tumor is a distinct entity with loss of BAP1 protein and epithelioid morphology. It shares histopathologic features with Spitz nevus and nevoid melanoma, and it can occur sporadically or with germline BAP1 predisposition syndrome. These lesions typically have tumor-infiltrating lymphocytes and infrequent mitoses. They are generally indolent, though melanoma can arise in both germline and sporadic cases. Most show BRAF V600E and BAP1 mutations. We describe four tumors in one patient diagnosed with BAP1-tumor predisposition syndrome (BAP1-TPDS): two invasive melanomas arising in BIMT and two BIMTs with uncertain malignant potential. Molecular analysis and fluorescence in situ hybridization (FISH) revealed BAP1 and NRAS mutations in melanoma and BAP1-inactivated melanocytic tumor components, with a gain of 6p25 (RREB1) in the melanoma component only. The patient completed pembrolizumab adjuvant therapy with no evidence of metastasis. This is a rare presentation of BIMT with BAP1 and NRAS mutations, absence of BRAF V600 mutation, and loss of BAP1 immunoreactivity in all lesional cells. Our case adds to the understanding of the histomorphologic and mutational spectrum in BAP1-inactivated melanocytic tumors.

In dermatopathology, mixed inflammatory patterns, such as mixed spongiotic and interface dermatitis (SID) are not well-characterized and can present a diagnostic challenge. This pattern can be seen in drug eruptions, viral exanthems, and syphilis infection. We present two cases of paraneoplastic erythroderma characterized by a mixed pattern SID. The patients underwent an extensive workup and were found to have positive antinuclear antibodies (ANA) in the absence of symptoms diagnostic of connective tissue disease. Eventually, the patients were both diagnosed with malignancies (systemic marginal zone lymphoma and breast cancer). It is important for dermatopathologists to consider paraneoplastic dermatitis in the differential diagnosis of mixed pattern SID, particularly in the clinical setting of erythroderma, as these findings can be the presenting sign of underlying malignancy. Additionally, if antinuclear antibodies are detected in the absence of classic clinical signs of connective tissue disease, a thorough workup should be conducted to exclude malignancy.

Congenital Spitz nevi have been rarely reported, and the diagnoses were usually based on the histopathological and immunohistochemical findings. We describe a case of a congenital Spitz tumor in which the molecular studies demonstrated a ZKSCAN1::MET fusion. No other somatic mutations and/or copy number variations outside of the MET gene were identified. Activating MET kinase rearrangements were previously reported only in a few cases of atypical Spitz tumors and spitzoid melanomas. Specifically, the ZKSCAN1::MET fusion was previously described in a single case of spitzoid melanoma demonstrating an uneventful course. Altogether, the histopathological, immunohistochemical, and molecular studies in our case supported a diagnosis of a congenital Spitz melanocytoma. This underscores the value of molecular analyses in Spitz tumors.

Proliferative neurocristic hamartoma (PNH), a rare variant of proliferative nodule, is a benign cutaneous proliferation with melanocytic, neurosustentacular, and mesenchymal differentiation that develops within a congenital or acquired melanocytic nevus. We report the case of a 38-year-old female who presented with a brownish-black plaque on the right medial sole that appeared during childhood and showed rapid nodular growth in the center over the past year. Histological examination revealed a well-demarcated dermal nodule characterized by spindle cell proliferation in a haphazard pattern in the center, with a congenital melanocytic nevus in the periphery. Immunohistochemical staining for S-100, SOX-10, HMB45, EMA, Glut-A, and CD34 demonstrated melanocytic, perineural, and fibrous differentiation in the central nodule, consistent with PNH. The mitotic activity was very low for the Ki-67 stain, and the PRAME stain was negative. Accurate pathological diagnosis is essential to reassure the patient of the nature of this changing mole and exclude the possibility of melanoma.