Dermatopathology, Volume 13, Issue 2 (June 2026) – 8 articles

Inflammatory skin diseases are characterized by complex interactions between immune pathways, epidermal barrier function, and environmental triggers, leading to distinct clinical and histopathological features. This narrative review aims to integrate current knowledge on the cutaneous immune microenvironment across major inflammatory skin diseases, including atopic dermatitis, psoriasis, hidradenitis suppurativa, and vitiligo. A comprehensive literature search was conducted using PubMed, Web of Science, and Scopus, focusing on studies published between 2021 and early 2026. The findings highlight disease-specific immune signatures, such as Th2-driven inflammation in atopic dermatitis, IL-23/Th17 axis activation in psoriasis, neutrophil-dominated responses in hidradenitis suppurativa, and cytotoxic T-cell-mediated melanocyte destruction in vitiligo. These molecular pathways are closely reflected in histopathological patterns, emphasizing the link between morphology and immunopathogenesis. Advances in targeted therapies, including biologics and Janus kinase inhibitors, demonstrate the clinical relevance of these pathways and support a transition toward mechanism-based treatment strategies. Dermatopathology is increasingly contributing to precision medicine approaches by supporting correlations between tissue features, immune pathways, and potential therapeutic targets. This review provides a framework for improved disease stratification and for the development of personalized treatment strategies in inflammatory skin diseases. Full article

Background and Objectives: Sentinel lymph node biopsy (SLNB) is increasingly used for high-risk, clinically node-negative cutaneous squamous cell carcinoma (cSCC), yet pathological reporting remains binary, lacking morphological stratification. The prognostic relevance of nodal tumor burden subtypes—isolated tumor cells (ITC), micrometastases, and macrometastases—is well established in melanoma and breast cancer but remains uncharacterized in cSCC. We aimed to describe the morphological spectrum of sentinel lymph node involvement in a consecutive institutional cohort and determine whether primary tumor characteristics predict the extent of nodal colonization. Materials and Methods: We conducted a retrospective-observational study at Clinical Center Niš (Serbia) including 35 consecutive clinically N0 high-risk cSCC patients who underwent SLNB using a dual-tracer protocol (⁹⁹mTc-labeled albumin and methylene blue). Sentinel nodes were processed by serial sectioning with hematoxylin-eosin and pancytokeratin (AE1/AE3) immunohistochemistry. Deposits were classified as ITC (≤0.2 mm), micrometastases (>0.2–2.0 mm), or macrometastases (>2.0 mm). Clinicopathologic predictors were evaluated using the Mann–Whitney U test, Fisher’s exact test, the Kruskal–Wallis test, and the Spearman rank correlation test. Results: SLN involvement was identified in 12 of 35 patients (34.3%). Among positive cases, ITC accounted for 6 patients (50.0%), micrometastases for 5 (41.7%), and macrometastasis for 1 (8.3%)—minimal nodal disease constituting 91.7% of positive findings. No primary tumor feature—including diameter, thickness, grade, perineural invasion, or lesion multiplicity—significantly distinguished ITC from overt metastatic deposits. Patients with ITC showed numerically higher median tumor thickness (8.0 mm) than those with micrometastases (4.0 mm), though this did not reach significance (Kruskal–Wallis p = 0.065). Conclusions: SLN positivity in high-risk cSCC is morphologically heterogeneous, with minimal nodal disease predominating. Primary tumor features do not reliably stratify the extent of nodal colonization. Structured tumor-burden reporting—distinguishing ITC, micrometastases, and macrometastases—should be adopted as standard practice to enable meaningful prognostic comparisons and inform individualized management. Full article

Granuloma annulare is a non-infectious granulomatous dermatosis with a probable pathogenic mechanism of delayed-type hypersensitivity, in which the dermal histiocytic granulomatous infiltrate is usually accompanied by a lesser component of lymphocytes. Although there are more common clinical and histopathological patterns of presentation, there are less well-known variants that may pose significant diagnostic challenges by mimicking other inflammatory cutaneous processes or even neoplastic conditions. One of the rarest forms of granuloma annulare is the pseudolymphomatous variant, in which the lymphocytic component is not only highly prominent but may, in some cases, partially or completely obscure the histiocytic component itself. This feature, together with the fact that the clinical presentation of this variant is often atypical—frequently lacking the characteristic annular morphology of conventional granuloma annulare—renders the diagnosis particularly challenging. From an immunohistochemical standpoint, the infiltrates described are predominantly composed of T cells, with only a sparse and scattered B-cell component. In this article, we present a case of granuloma annulare with a pseudolymphomatous B-cell component (PAX5⁺, CD79⁺) and minimal T-cell involvement, observed in a 4 mm skin nodule located on the shoulder of a 48-year-old male. This case therefore broadens the concept of pseudolymphomatous granuloma annulare to include infiltrates predominantly composed of B lymphocytes. Full article

An 86-year-old man presented with a slowly enlarging, subject to chronic mechanical irritation, pedunculated keratotic papule on the plantar tip of the right hallux in the setting of severe peripheral arterial disease. Excision was deferred until after endovascular revascularization to reduce the risk of nonhealing and limb complications, after which the lesion was removed without wound sequelae. Histopathology demonstrated a conical papule with a central collagenous core and an overlying cap of compact hyperkeratosis. This case highlights key clinicopathologic features that distinguish acral keratotic tumors and underscores the importance of perfusion optimization when planning elective excision on an ischemic limb. Full article

Desmosomes are specialized cell–cell junctions that play a crucial role in maintaining the structural integrity of both cornifying and non-cornifying epithelium. Disruption of desmosomal cohesion in autoimmune, infectious, and other diseases is typically associated with acantholysis, often leading to intraepidermal blisters and erosions. In recent decades, genetic mutations have been identified that impair desmosomal integrity to varying degrees, giving rise to a spectrum of genodermatoses. These conditions, which include palmoplantar keratoderma, epidermolysis bullosa, and ichthyoses, can range from mild to severe, with some forms being syndromic and life-threatening. We investigated dermatopathologic changes in patients with mutations in genes encoding desmosomal proteins seen in consultations at our genodermatoses unit. A series of cases, including keratosis palmoplantaris areata et striata (striated palmoplantar keratoderma type 1), Carvajal–Huerta syndrome, severe dermatitis–multiple allergies–metabolic wasting (SAM) syndrome, ectodermal dysplasia–skin fragility syndrome, and inflammatory peeling skin disease, was examined histologically and, when necessary, immunohistochemically. Findings from our cohort were compared with histopathological consultation cases from our dermatopathology laboratory and previously published cases in the literature. Through these observations, we defined a distinct form of acantholysis associated with desmosomal protein mutations, which we term “desmosomal-type acantholysis.” We outline the spectrum of this newly characterized pattern and highlight its differences from conventional forms of acantholysis. Furthermore, for the first time, we describe incidental cases where “desmosomal-type acantholysis” appears sporadically in solitary acanthoma and in association with a melanocytic nevus. Full article

Blastomycosis-like pyoderma (BLP) is a rare chronic inflammatory dermatosis characterized by exuberant vegetative and verrucous plaques, most frequently associated with bacterial colonization, particularly Staphylococcus aureus. Owing to its striking clinical and histopathological resemblance to squamous cell carcinoma (SCC) and other granulomatous or hyperplastic dermatoses, BLP represents a well-recognized diagnostic pitfall, often leading to delayed diagnosis or unnecessary surgical management. We report an unusual case of bilateral auricular BLP in a 58-year-old apparently immunocompetent woman, initially misdiagnosed as SCC. Comprehensive clinicopathological reassessment revealed pseudoepitheliomatous hyperplasia, intraepidermal neutrophilic microabscesses, and a dense mixed inflammatory infiltrate, findings consistent with a reactive rather than neoplastic process. Microbiological cultures confirmed Staphylococcus aureus, supporting the final diagnosis of BLP and guiding effective antimicrobial therapy. To better contextualize this rare presentation, we reviewed all previously reported cases of BLP, summarizing available clinical, histopathological, microbiological, and therapeutic data. This case further raises the possibility of an association between BLP and systemic inflammatory conditions, as the patient subsequently developed severe colitis, highlighting the potential role of immune dysregulation and the gut–skin axis in disease pathogenesis or a possible temporal association, without allowing causal inference. Beyond inflammatory bowel disease, blastomycosis-like pyoderma has been reported in association with a variety of systemic and immune-mediated conditions, including diabetes mellitus, hematologic malignancies, HIV infection, chronic renal failure, autoimmune disorders, and prolonged immunosuppressive therapies. These associations support the concept that BLP represents a hyperinflammatory reaction pattern occurring in the setting of altered immune surveillance rather than a purely infectious disease. Accurate recognition and management of BLP require careful integration of clinical features, histological findings, and microbiological results. Increased awareness of its diverse presentations is essential to avoid misdiagnosis and to ensure appropriate, conservative treatment. Full article

Cutaneous adnexal carcinomas (CACs) comprise a diverse group of malignant tumors that show morphological differentiation toward one of the four main adnexal structures in normal skin: hair follicles, sebaceous glands, sweat-apocrine glands, and sweat-eccrine glands. These tumors can arise sporadically or may be associated with rare genetic syndromes. A total of 276 CACs cases underwent hybrid capture-based comprehensive genomic profiling (CGP) to assess all classes of genomic alterations (GA). Sequencing data were used to determine microsatellite instability (MSI) status, tumor mutational burden (TMB), genomic loss of heterozygosity (gLOH), genomic ancestry, and COSMIC mutational signatures. PD-L1 expression was evaluated by immunohistochemistry (TPS; Dako 22C3). Statistical analyses were performed using Fisher’s exact test, with false discovery rate correction via the Benjamini–Hochberg method. Sequencing was performed on primary cutaneous tumors in 131 cases (47.4%) and on local recurrence or metastatic site biopsies in 145 cases (52.5%). Across all groups, there was a male predominance (64–81%) and similar mean ages (59–63 years), with apocrine (APO) tumors occurring in older patients than eccrine (ECC) tumors (72 vs. 62 years; p = 0.001). Histologically, 173 tumors (62.7%) were sweat gland-derived (SWT), 55 (19.9%) sebaceous gland-derived (SEB), 14 (5.1%) hair follicle-derived (HRF), and 34 (12.3%) unclassified (UNK). Among SWT tumors, 150 (86.7%) were eccrine and 23 (13.3%) apocrine. SWT tumors included digital papillary adenocarcinomas (DPA, 6.9%), mucinous carcinomas (MC, 6.3%), porocarcinomas (POR, 11.0%), spiradenocarcinomas (SPR, 8.1%), syringoadenocarcinomas (SRNG, 5.8%), and 77 (44.5%) unclassified cases. The number of GA per tumor was highest in SEB compared with SWT tumors (7.9 vs. 4.9; p = 0.005) and lowest in DPA (2.1 vs. 5.0 in non-DPA; p = 0.03). No differences in ancestry distribution were observed. Compared with SWT tumors, SEB tumors exhibited higher frequencies of RB1 (38.2% vs. 8.1%; p < 0.0001) and TP53 alterations (76.4% vs. 43.4%; p = 0.0002), suggesting potential neuroendocrine differentiation. MC tumors showed significantly higher PTCH1 alterations than non-MC tumors (36.4% vs. 1.8%; p = 0.044). MSI-high status was most frequent in SEB tumors compared with all other groups (15.7% vs. 1.2%; p = 0.005), and gLOH > 16% was also more common in SEB than SWT tumors (19.6% vs. 7.2%; p = 0.081). The MMR signature occurred more frequently in SEB than SWT tumors (32.0% vs. 2.1%; p = 0.005). Mean TMB was elevated across most CACs types, ranging from 10.4 mutations/Mb in HRF to 38.8 mutations/Mb in MC, with the exceptions of APO (2.7 mut/Mb; p = 0.001) and DPA (1.4 mut/Mb; p = 0.003). PD-L1 expression was generally low and did not differ significantly between SWT and SEB tumors (37.0% vs. 33.3%; NS). Given the limited data on CAC treatment, this study provides a catalog of commonly observed GA. SEB tumors exhibited the highest frequency of genomic alterations. Prospective clinical trials are needed to determine the prognostic and predictive value of CAC-specific biomarkers for immune checkpoint inhibitor (ICI) response, which is essential for integrating novel therapies into the evolving treatment landscape. Full article