Dermatopathology

Melanoma subtyping plays a vital role in histopathological diagnosis, informing prognosis and, in some cases, guiding targeted therapy. However, conventional histologic classification is constrained by inter-rater reliability, morphologic overlap, and the underrepresentation of rare subtypes. Deep learning (DL)—particularly convolutional neural networks (CNNs)—presents a compelling opportunity to enhance diagnostic precision and reproducibility through automated analysis of histopathologic slides. This review examines the clinical importance and diagnostic challenges of melanoma subtyping, outlines core DL methodologies in dermatopathology, and synthesizes current advances in applying DL to subtype classification. Pertinent limitations including dataset imbalance, a lack of interpretability, and domain generalizability are discussed. Additionally, emerging directions such as multimodal integration, synthetic data generation, federated learning, and explainable AI are highlighted as potential solutions. As these technologies mature, DL holds considerable promise in advancing melanoma diagnostics and supporting more personalized, accurate, and equitable patient care. Full article

A 56-year-old patient presented to our dermatology clinic with asymmetric hyperpigmentation on her lower lip, which had developed over the previous six to twelve months. Her medical history included kidney and pancreas transplants, requiring chronic immunosuppression, and two lip filler injections with hyaluronic acid (HA). Clinical examination revealed irregular pigmented macules limited strictly to the lower lip. Histological analysis showed epidermal melanosis, pigmentary incontinence, solar elastosis, and amorphous dermal HA deposits, without evidence of melanocytic hyperplasia or granulomatous inflammation. Full article

We report the case of a 16-year-old girl presenting with a painless, clinically stable subcutaneous swelling of the nasal dorsum with a three-year history. Despite an extensive multidisciplinary diagnostic work-up—including dermatological, otorhinolaryngological, and radiological evaluations (ultrasound, CT, and MRI)—the nature of the lesion remained indeterminate. In order to achieve a definitive diagnosis while preserving the nasal profile aesthetics, the mass was entirely excised via an endoscope-assisted closed rhinoseptoplasty approach. Histopathological analysis revealed a spindle cell lipoma characterized by CD34 positivity and a Ki-67 proliferation index of less than 1%. This finding is extremely rare in terms of both anatomical location and patient age. The present case highlights the crucial role of histopathological examination in establishing the correct diagnosis, supported by a multidisciplinary assessment. Full article

Encephalocraniocutaneous lipomatosis (ECCL) is a rare congenital neurocutaneous disorder characterized by ocular, skin, and central nervous system manifestations. Despite its recognizable clinical features, such as nevus psiloliparus, histopathologic characterization of ECCL remains limited in the dermatopathology literature, and diagnosis is often clinical. This scarcity of published histopathological descriptions makes diagnostic confirmation challenging and underscores the value of synthesizing the available evidence. This comprehensive review synthesizes reported histopathological findings across cutaneous manifestations highlighting key tissue-level features that may aid diagnostic confirmation. Additionally, we review the emerging role of molecular diagnostics, particularly the identification of mosaic activating mutations in FGFR-1 and KRAS, which have been implicated in ECCL pathogenesis. By integrating clinicopathologic correlations with molecular insights, this review aims to enhance our dermatopathological understanding of ECCL, bolstering diagnostic reasoning and clinical decision making for this rare neurocutaneous condition. Full article

Background/Objectives: Oral focal mucinosis (OFM) and solitary cutaneous focal mucinosis (SCFM) are rare, benign lesions characterized by localized mucin deposition in the stromal connective tissue. While both share similar histological features, they occur in distinct anatomical sites and clinical contexts and have not been directly compared in the literature. Method: This study presents a case series of 39 OFM cases diagnosed over 25 years, supplemented by a literature review of previously reported OFM cases, and compares the combined data with published cases of SCFM. The literature-based analysis included 116 OFM cases published in four articles and 138 cases of SCFM published in five articles. Demographic and clinical data were extracted and analyzed, including age, sex, lesion location, size, duration, symptoms, clinical impression, treatment, and recurrence. Results: The mean age of OFM patients was 41 years, with a slight female predominance, most commonly affecting the gingiva. SCFM cases were more common in males, with a higher mean age of 52 years and frequent occurrence on the extremities and trunk. Both lesions were predominantly asymptomatic and managed by conservative excision. Due to its rare occurrence and nonspecific clinical presentation, both entities were frequently clinically misdiagnosed. Conclusions: In conclusion, this is the first study to directly compare OFM with SCFM and represents the largest series of OFM reported to date. The study provides new comparative insights into SCFM and OFM, highlighting differences in age, gender, lesion site, size, and symptomatology. SCFM predominantly affects older males on the extremities, whereas OFM occurs in younger females, mainly in the gingiva, with larger, sometimes symptomatic lesions, and with a very low recurrence rate. Full article

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

A 27-year-old female with no significant medical or dermatologic history presented with a persistent acneiform eruption on the face. The patient had been treated with multiple topical and systemic anti-acne treatments with no significant improvement over a period of two years. A punch biopsy was performed on the right cheek lesion showing dense lymphocytic infiltrates of the reticular dermis with peri- and intra-follicular distribution. Full article

Despite therapeutic advancements, malignant melanoma remains a leading cause of skin cancer-related mortality, with incidence continuing to rise globally. Traditional prognostic tools offer important clinical guidance but fail to capture the biological heterogeneity of melanoma or reliably predict responses to emerging therapies. In this review, we summarize recent advances in prognostic and predictive molecular biomarkers reported over the past five years. We discuss immunohistochemical and tissue-based markers, circulating biomarkers, microRNAs, and gene expression profiles that enhance risk stratification and inform surveillance strategies. We also review immune-related markers that may predict response to immune-checkpoint inhibitor therapy. Lastly, we highlight investigational biomarkers—including gene signatures, epigenomic alterations, and microbiome influences—that are shaping the future landscape. Together, these advances reflect a shift toward precision oncology in melanoma, with the integration of biomarker-driven strategies offering the potential to personalize treatment and improve patient outcomes. Full article

Stratum Corneum (SC) formation in the human epidermis requires lipid processing. Lipoxygenases (LOXs) such as 12R-Lipoxygenase (12R-LOX) and Epidermis-type lipoxygenase 3 (eLOX-3) contribute to this process. Mutations in their genes cause Autosomal Recessive Congenital Ichthyosis (ARCI) in patients. On the other hand, 12S-lipoxygenase (12S-LOX) is expressed in the human epidermis, but its role still remains to be clarified. The involvement of eLOX-3, 12R, and 12S-LOX in conditions or processes such as skin photodamage, wound healing, psoriasis, and atopic dermatitis is suggested but still remains unclear. In order to eventually gain a better understanding of the role of these LOXs in such processes, models of Tissue-Engineered Skins (TESs) with an impaired expression for the native form of either eLOX-3, 12R-LOX, or 12S-LOX were produced using CRISPR-Cas9(D10A) technology. All three models showed impaired keratinocyte differentiation and changes in the prevalence or the size of lipid droplets within the most superficial layers, thus reproducing features observed in ARCI and supporting a role for 12S-LOX in SC formation. Since eLOX-3 and 12R-LOX depleted TES’s reproduced features observed in ARCI, such models can be considered as reliable tools for the functional studies of these LOXs in the human epidermis. Full article

Introduction: Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma, often exhibiting loss of pan-T-cell markers such as CD2, CD3, CD5, and CD7. While these immunophenotypic alterations assist in diagnosis, their prognostic relevance in early-stage MF remains uncertain. This study aimed to determine whether immunohistochemical loss of T-cell markers CD2, CD3, CD5, and CD7 in patients with early-stage mycosis fungoides is associated with overall survival and progression-free survival. Methods: This retrospective included 83 patients with stage IA–IIA MF diagnosed between 2003 and 2012 at a single institution. Immunohistochemical staining of archived biopsy specimens was performed for CD2, CD3, CD5, and CD7. Loss of marker expression was defined as absence in ≥30% of lymphocytes. Clinical and histopathological data were correlated with survival and progression outcomes using Kaplan–Meier curves and log-rank tests. Results: Loss of at least one T-cell marker was identified in 66% of patients, most commonly CD7 (72%), followed by CD5 (11%) and CD2 (11%). No cases showed loss of CD3 expression. CD7 loss was significantly associated with shorter progression-free survival (p < 0.05), but not with overall survival. No significant associations were found between CD2 or CD5 loss and either survival or disease progression. Conclusions: CD7 loss was the only immunohistochemical abnormality significantly associated with earlier disease progression in early-stage MF, suggesting a potential prognostic role. In contrast, loss of CD2 and CD5 did not affect survival or progression, and CD3 was preserved in all cases. These findings highlight the value of incorporating CD7 status into prognostic assessment, although larger studies are needed to confirm its utility. Full article

Dermatofibroma is a common mesenchymal skin lesion that typically presents as a firm, slow-growing nodule. Generally, such lesions are asymptomatic; however, they can also cause discomfort in some cases. Ulceration is an uncommon feature of dermatofibroma, and diagnosis in such cases is often difficult. We report a case of a 67-year-old female with multiple comorbidities, including pancreatic cancer undergoing neoadjuvant chemotherapy, who was admitted for acute pulmonary embolism. The patient presented with an incidental medial thigh lesion. The lesion was asymptomatic, ulcerated, and oozing pus one month before presentation. Clinical examination revealed a 3 × 2 cm deep ulcer with a punched-out edge, a dry yellow-white base, and a firm violaceous border. Histopathology confirmed dermatofibroma with epidermal hyperplasia, dermal spindle cell proliferation, histiocytes, and collagen trapping. Immunohistochemistry was positive for CD68, CD10, and Factor XIII. Due to the deteriorating condition of the patient, no intervention was provided to her, and she succumbed to her primary illness. This case is unique due to its atypical ulcerative presentation in a patient with complex systemic illness and emphasizes distinguishing between benign lesions and malignant mimics, especially in cases which have ambiguous clinical presentation. Full article

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory disease with a complex immune response. Given the considerable heterogeneity of the clinical phenotype of HS, this study aimed to analyse the immunohistochemical pattern of interstitial inflammation. Methods: Immunohistochemical analysis was performed on skin samples from 49 patients with HS. The immunohistochemical markers CD3, CD4 and CD8 for T-cells, CD20 for B-cells, CD138 for plasma cells and CD30, CD56, Bcl-2 and Bcl-6 were stained on lesional skin. Results: The analysis of immune cell dominance in patients with HS revealed that 33.3% of the cohort exhibited B-cell dominance, defined as a ratio of the sum of CD20+ and CD138+ cells to CD3+ cells greater than 1, while the majority (66.7%) demonstrated T-cell dominance, defined as a ratio of CD3+ cells to the sum of CD20+ and CD138+ cells greater than 1. B-cell-dominant HS is associated with a significantly elevated probability of mammary involvement (13.3% vs. 0%; p = 0.041). T-cell-dominant HS patients tended to demonstrate a higher mean tobacco consumption, but not significantly (20 vs. 5 tobacco pack-years; p = 0.06). CD4-dominant HS patients exhibited a significantly greater involvement of the mons pubis (62.5% vs. 28.6%, p = 0.023) compared to CD8-dominant patients, who demonstrated a significantly higher number of abscesses (p = 0.027). Conclusions: For the first time, we describe the clinical and immunohistochemical characteristics of T-cell- and B-cell-dominant HS. Although HS seems to be more dominated by T-cells, a B-cell dominance was found in 33% of cases. Full article

Pilomatricomas are benign tumors originating from hair follicle matrix cells and represent the most common skin tumors in pediatric patients. Pilomatricomas may be associated with genetic syndromes such as myotonic dystrophy, familial adenomatous polyposis (FAP), Turner syndrome, Rubinstein–Taybi syndrome, Kabuki syndrome, and Sotos syndrome. This study reviews the literature on pilomatricomas occurring in syndromic contexts and presents a novel case linked to Apert syndrome. A systematic review was conducted using PubMed and Cochrane databases, focusing on case reports, case series, and reviews describing pilomatricomas associated with syndromes. A total of 1272 articles were initially screened; after removing duplicates and excluding articles without syndromic diagnoses or lacking sufficient data, 81 full-text articles were reviewed. Overall, 96 cases of pilomatricomas associated with genetic syndromes were identified. Reports of patients with Apert syndrome who do not develop pilomatricomas are absent in the literature. Pilomatricomas predominantly affect pediatric patients, with a slight female predominance, and are often the first manifestation of underlying genetic syndromes. Our study highlights previously unreported associations of pilomatricoma with Apert syndrome, providing molecular insights. This study contributes to understanding the clinical and molecular features of pilomatricomas in syndromic contexts and underscores the importance of genetic analysis for accurate diagnosis and management. Full article