Dermatopathology, Volume 12, Issue 4 (December 2025) – 5 articles

Neurofibromatosis type 1 (NF1) is a prevalent neurocutaneous illness resulting from mutations in the NF1 gene, usually diagnosed according to clinical criteria set by the National Institutes of Health (NIH). These encompass café-au-lait macules, axillary freckling, Lisch nodules, ocular gliomas, osseous lesions, neurofibromas, and familial history. Atypical instances exhibiting partial or isolated characteristics, such as numerous cutaneous neurofibromas (cNFs) absent other classical manifestations, provide a diagnostic difficulty and may be little acknowledged in clinical environments. We describe a 47-year-old male with several soft, non-tender, pinkish-red papules and nodules dispersed throughout the face, torso, limbs, and back. A solitary café-au-lait macule measuring 3 x 2 cm was seen below the right breast, no axillary or inguinal freckling was observed, Lisch nodules were absent during ophthalmologic examination, and there was no pertinent family history. The histopathological examination of a skin lesion verified the diagnosis of cutaneous neurofibroma. According to the NIH guidelines, the patient did not satisfy the requirements for a conclusive diagnosis of NF1. This instance underscores the clinical intricacy of NF1 spectrum diseases and suggests the potential for mosaic NF1 or a minor phenotypic variation. The existence of several cNFs without systemic involvement undermines the adequacy of existing diagnostic paradigms, particularly in adults who exhibit no early-life signs. The psychosocial challenges linked to widespread cNF distribution highlight the necessity for a comprehensive assessment. Limitations encompass the lack of genetic testing, which would have facilitated the confirmation of the diagnosis and the assessment of probable mosaicism. Isolated cutaneous neurofibromas, devoid of other conventional NF1 characteristics, are an uncommon yet clinically pertinent manifestation. Clinicians must uphold a heightened level of suspicion for aberrant NF1 phenotypes and contemplate further examination, using molecular diagnostics where feasible. Reevaluating diagnostic criteria to include these polymorphisms is essential for prompt identification, effective care, and enhanced patient outcomes. Full article

Dermatofibromas (DFs) are benign neoplasms of the dermis typically found on the extremities of young adults. In approximately 3–5% of cases, basaloid cell hyperplasia (BCH) is observed overlying DFs. BCH is characterized by the proliferation of basaloid cells within the epidermis. BCH and superficial basal cell carcinoma (BCC) share many histological features, making their differentiation challenging. It is therefore unclear if the proliferation of basaloid cells in DFs represents an inductive process or, conversely, a malignant transformation indicative of BCC. The primary objective of our study was to determine whether BCH can be distinguished from superficial BCC using histology and immunhistological techniques. The histological and immunohistochemical characteristics of 43 DF samples with overlying BCH revealed significant similarities in staining patterns with those of superficial BCC described in the literature. These findings point to the need for innovative methods, such as molecular techniques, to refine diagnostic accuracy. Full article

Acroangiodermatitis is an uncommon angioproliferative dermatosis, related to chronic circulatory diseases, such as chronic venous insufficiency and arteriovenous malformations. We describe the case of a 32-year-old healthy male presenting with a pruritic, brownish lesion on the dorsal surface of the left foot, evolving for ten years. Physical examination revealed a brown plaque, with a verrucous surface, on the distal dorsum and medial border of the left foot. Histopathology disclosed a marked neovascularization of the upper dermis, associated with erythrocyte extravasation and hemosiderin deposition. Immunochemistry for HHV-8 was negative. CT angiography revealed multiple serpiginous vessels on the dorsum of the left foot, suggestive of a venous malformation. The diagnosis of acroangiodermatitis was established and the patient started topical corticosteroids and compression stockings, without improvement. Although scarcely described in the literature, treatment with PDL was proposed given the vascular proliferation confined to the papillary dermis. After two sessions, a significant improvement was observed. This case emphasises dermatopathology as the gold standard for the differential diagnosis with Kaposi sarcoma. In addition, it highlights PDL as a promising therapeutic option, based on the superficial histopathological location. Full article

There are many benign skin neoplasms encountered in dermatopathology practice that can be associated with underlying genetic disorders. Although benign themselves, these lesions can offer insight into the potential for development of internal malignancies in patients with these hereditary syndromes. An astute dermatopathologist will recognize clues that suggest a syndromic association of these lesions, such as the presence of multiple lesions, distinct histologic growth patterns, and the results of ancillary immunohistochemical testing. The dermatopathologist can then guide the referring clinician to obtain additional clinical and family history and, if appropriate, pursue further screening and genetic testing. This review article will provide an overview of the clinical and histologic features associated with select common and uncommon benign skin neoplasms with syndromic associations. Full article

Human herpesvirus-8 (HHV-8)-associated multicentric Castleman disease (MCD) is a rare lymphoproliferative disorder with systemic and cutaneous manifestations that can be diagnostically challenging, especially in immunocompromised patients. We report the case of a 68-year-old man with HIV and biopsy-proven Kaposi sarcoma (KS), who developed progressive fevers, night sweats, weight loss, and fatigue, accompanied by diffuse lymphadenopathy, splenomegaly, and new erythematous and hyperpigmented lesions shortly after intravenous immunoglobulin therapy for Guillain–Barré syndrome. A laboratory evaluation revealed that the patient had elevated total protein and polyclonal hypergammaglobulinemia, without monoclonality. Imaging demonstrated widespread lymphadenopathy and splenomegaly. A core lymph node biopsy showed polytypic plasmacytosis, but was non-diagnostic. Given the ongoing symptoms, an excisional biopsy was performed, revealing regressed germinal centers with increased interfollicular vascularity, mantle zone “onion skinning,” and HHV-8 LANA-1 nuclear positivity, establishing the diagnosis of HHV-8-associated MCD. Rituximab monotherapy was initiated, resulting in clinical improvement, resolution of the constitutional symptoms, and stabilization of ascites. This case highlights the importance of maintaining a high index of suspicion for MCD in patients with KS who develop new systemic or cutaneous findings, the limitations of a core biopsy, and the value of a timely excisional biopsy in guiding diagnosis and treatment. Full article