Am J Dermatopathol
· 2026 Jun · PMID 42331601
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Melanoma in situ on chronically sun-damaged skin may extend significantly beyond clinically visible borders. Immunohistochemistry, particularly PRAME (PReferentially expressed Antigen in MElanoma), has emerged as a usefu...Melanoma in situ on chronically sun-damaged skin may extend significantly beyond clinically visible borders. Immunohistochemistry, particularly PRAME (PReferentially expressed Antigen in MElanoma), has emerged as a useful adjunct in delineating subclinical spread of lentigo maligna-type melanoma in situ. We report a case illustrating the diagnostic challenge of determining margins for melanoma in situ of lentigo maligna type even with the benefit of PRAME immunohistochemistry.
Am J Dermatopathol
· 2026 Jun · PMID 42331555
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The spectrum defining T-cell-mediated alopecias is an expression of autoimmune, innate, regenerative, and effete pathophysiological pathways. Four main folliculotropic T-cell patterns can be integrated into clinicopathol...The spectrum defining T-cell-mediated alopecias is an expression of autoimmune, innate, regenerative, and effete pathophysiological pathways. Four main folliculotropic T-cell patterns can be integrated into clinicopathologic aspects and define the majority of these alopecias. Lymphocytic inflammation targeting bulbs defines alopecia areata, and pan follicular lymphocytes sparing the hair bulbs and perifollicular concentric fibrosis define lichen planopilaris. Non-destructive lymphocytic folliculitis localized to the bulge modulating stem cell function is introduced as an unrecognized spectrum without defined alopecia. Pan follicular lymphocytic alopecia targets all levels of the follicle, including the bulb and sebaceous glands, and occurs in lupus erythematosus, follicular mucinosis, folliculotropic T-cell dyscrasia, and lymphoma. These form an evidence-based platform due to their inherent programmed pathways. Major advances have occurred in defining inducible mesenchymal skin associated with lymphoid tissue incorporating the pleiotropic functions of regulatory T cells integrated into the JAK/STAT activating transducer pathway. Beyond immunology, the integrated Tregs have non-immunologic functions that modulate stem cell pathways, regulate follicular cycles and follicular inflammation, and repair. In all T-cell alopecias, the central role of both CD8+ and Treg memory cells is pivotal in creating local, multifocal, and diffuse patterns of hair loss. The relationship between the stem cell niche localized to the bulge and supported by the stem cell niche forming progenitor bulbs that induce rapid transit amplifying basaloid cells and trichogenesis are explored in reference to both physiologic and pathogenic pathways. The expanding evidence-based studies defining the pleiotropic functions of the iSALT incorporated Treg/JAK/STAT pathways have led to the development of a conceptual framework to address T-cell alopecias.
Nodular granulomatous phlebitis is an exceptionally rare and probably underdiagnosed form of tuberculid. It is characterized by granulomatous inflammation centered on the walls of subcutaneous veins and may clinically mi...Nodular granulomatous phlebitis is an exceptionally rare and probably underdiagnosed form of tuberculid. It is characterized by granulomatous inflammation centered on the walls of subcutaneous veins and may clinically mimic panniculitis or superficial thrombophlebitis. We report a new case of this entity together with a comprehensive review of the literature to better delineate its clinical and histopathologic spectrum. This is a poorly recognized tuberculid in which histopathologic findings are essential for establishing the diagnosis. Awareness of this pattern is particularly important for both dermatologists and pathologists, because failure to recognize it may lead to inappropriate immunosuppressive treatment and the consequent risk of reactivation of latent tuberculosis.
Interestingly, ossification is a rare histopathologic feature in chondroid syringoma, a benign cutaneous adnexal tumor consisting of mixed ductal and chondromyxoid differentiation. We report two cases of chondroid syring...Interestingly, ossification is a rare histopathologic feature in chondroid syringoma, a benign cutaneous adnexal tumor consisting of mixed ductal and chondromyxoid differentiation. We report two cases of chondroid syringoma with pronounced ossification. A 46-year-old Hispanic woman presented with a slowly enlarging, asymptomatic, erythematous nodule on the left upper cutaneous lip abutting the nasal sill. Excisional biopsy revealed a well circumscribed, subcutaneous, biphasic proliferation of ductal epithelial strands and chondromyxoid stroma with prominent trabecular ossification enclosing fatty marrow. The second case was a 76-year-old Native American woman with a progressively growing, erythematous nodule on the posterior neck. Histopathology of the excision demonstrated an encapsulated, subcutaneous, ossified tumor with peripheral eccrine ductal epithelium situated in chondroid matrix with sparse hematopoiesis. The patients exhibited no evidence of recurrence after 2 and 23 months, respectively. To date, nine cases of ossified chondroid syringoma have been published, without evidence of recurrence or malignant transformation. The etiology of osseous metaplasia in chondroid syringomas might occur due to differentiation of pluripotent stem cells. Elevated bone morphogenic protein in modified myoepithelial and stromal cells may be responsible for endochondral osteogenesis in chondroid syringoma. Osseous metaplasia with internal hematopoiesis is also a rare, yet benign finding. Our cases featuring exuberant osseous metaplasia add to the limited reports of this phenomenon co-occurring in patients identifying as Hispanic and Native American. Careful evaluation of cytology and architecture is essential to rule out aggressive mimicking tumors such as atypical or malignant chondroid syringoma, mucinous carcinoma, or metastatic adenocarcinoma with bone invasion.
Scleromyxedema is a rare, chronic cutaneous mucinosis defined histopathologically by a triad of dermal mucin deposition, fibroblast proliferation, and dermal fibrosis. However, additional underrecognized histopathologic...Scleromyxedema is a rare, chronic cutaneous mucinosis defined histopathologically by a triad of dermal mucin deposition, fibroblast proliferation, and dermal fibrosis. However, additional underrecognized histopathologic patterns or findings may complicate diagnosis and lead to misclassification. A retrospective review of 22 biopsy-confirmed cases of scleromyxedema was performed to characterize both classic and uncommon histopathologic variants of scleromyxedema, with emphasis on patterns that may obscure or mimic other dermatologic entities. All cases were evaluated for mucin, fibrosis, fibroblast proliferation, inflammatory infiltrates, granulomas, eosinophilic infiltration, and eccrine gland hyperplasia using hematoxylin and eosin and special stains, with immunohistochemistry as it was needed. Sixteen cases (72.7%) demonstrated the classic histologic triad. In contrast, 6 cases (27.3%) showed a granulomatous pattern characterized by interstitial collections of CD68+ histiocytes, multinucleated giant cells, sparse lymphocytes, and mucin, but lacked the full classical triad-posing a risk of misdiagnosis as granuloma annulare or other granulomatous dermatoses. Eosinophilic infiltrates were identified in 4 cases (18.2%), and eccrine gland hyperplasia in 2 cases (9.1%). Both findings coexisted with the classical triad and may mimic inflammatory or adnexal conditions. Scleromyxedema presents with broader histopathologic variability than classically recognized. The granulomatous pattern, which may lack the defining triad, can obscure diagnosis without clinical correlation. In contrast, eosinophilic infiltration and eccrine gland hyperplasia, though infrequent, typically coexist with classic features and should be recognized as part of the histologic spectrum. Awareness of these variants is essential to avoid misdiagnosis and ensure accurate clinicopathologic interpretation.
Stegura C, Steevens N, Neimy H
… +11 more, Saravanan S, Andrade M, Morgan H, Broughton L, Keller K, Almutairi Y, Huang Y, Al Nasseri T, Gregoski MJ, Valdebran M, Elston D
Am J Dermatopathol
· 2026 Jun · PMID 42307489
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Distinguishing malignant melanoma (MM) from benign melanocytic nevi presents a diagnostic challenge that can result in suboptimal management. We sought to assess whether quantifying nuclear and nucleolar areas in histolo...Distinguishing malignant melanoma (MM) from benign melanocytic nevi presents a diagnostic challenge that can result in suboptimal management. We sought to assess whether quantifying nuclear and nucleolar areas in histological samples provided utility in differentiation. Our study used deidentified hematoxylin and eosin (H&E)-stained teaching slides, 77 MM cases and 73 benign nevi cases (N = 150). Using ImageJ software, 20 nuclei and their corresponding nucleoli were measured per slide in square pixels and converted to square microns. Nuclei selection was contingent on visualization of the nuclear envelope and a singular nucleolus. Mann-Whitney U tests were applied to compare average nuclear and nucleolar areas between groups. Significant differences were observed in both nuclear and nucleolar areas. The mean nuclear area was significantly larger in MM compared with benign nevi (702.04 ± 236.55 μm2 vs. 481.18 ± 153.89 μm2; P < 0.001). Similarly, the mean nucleolar area was markedly larger in MM compared with benign nevi (90.88 ± 52.25 μm2 vs. 58.03 ± 25.35 μm2; P < 0.001).
Am J Dermatopathol
· 2026 Jun · PMID 42299752
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Hidradenomas are benign adnexal neoplasms with eccrine or apocrine differentiation. They typically present as slow-growing, nodular, well-circumscribed lesions that may be solid, cystic, or mixed in composition. These tu...Hidradenomas are benign adnexal neoplasms with eccrine or apocrine differentiation. They typically present as slow-growing, nodular, well-circumscribed lesions that may be solid, cystic, or mixed in composition. These tumors most commonly arise on the head, neck, or extremities, although they may occur at virtually any anatomical site. Hidradenomas are generally small, usually measuring up to 3 cm in diameter, and occurrence in the periarticular region is not uncommon, with reports of hidradenomas arising near joints such as the ankle, elbow, and knee documented in the literature. In this study, we report a case of a giant nodular hidradenoma with extensive cystic degeneration presenting as a progressively enlarging, painless knee mass after a traumatic injury. At 17.6 cm, this represents 1 of the largest hidradenomas reported in the literature, and highlights the diagnostic challenges posed by large cystic adnexal tumors arising in atypical periarticular locations.
Kalmykova A, Harnisch K, Chepets O
… +3 more, Stovbyr A, Artymko I, McKee P
Am J Dermatopathol
· 2026 Jun · PMID 42299730
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Langerhans cell histiocytosis (LCH) is a rare myeloid neoplastic disorder driven by somatic MAPK pathway mutations, most commonly BRAFV600E, characterized by clonal proliferation of CD1a+/CD207+ dendritic cells forming g...Langerhans cell histiocytosis (LCH) is a rare myeloid neoplastic disorder driven by somatic MAPK pathway mutations, most commonly BRAFV600E, characterized by clonal proliferation of CD1a+/CD207+ dendritic cells forming granulomatous lesions in various tissues. Nail involvement is an uncommon but clinically significant manifestation, often associated with multisystem disease and a potentially poorer prognosis. We report 2 pediatric cases of LCH presenting with nail changes as the initial clinical feature. Case 1, a 2-year-old boy, was presented with longitudinal grooving, onycholysis, subungual hyperkeratosis, and purpuric striae of nearly all fingernails. Staging investigations revealed only mild lymphadenopathy, and BRAF mutation testing was negative. He was treated with methylprednisolone and vinblastine, achieving metabolic inactivity at 9 months. Case 2, a 19-month-old boy, was presented with diffuse fingernail and toenail dystrophy followed by cutaneous papules and was found to have multisystem disease involving bone and lungs. Nail bed, skin, and bone biopsies confirmed LCH. Systemic chemotherapy with vinblastine and prednisone led to marked improvement in nail, skin, pulmonary, and osseous lesions. These cases illustrate that nail changes may be the earliest manifestation of LCH and should prompt thorough systemic evaluation. Early recognition of nail involvement can facilitate timely diagnosis and risk-adapted treatment, potentially improving outcomes in affected patients.
Triyangkulsri K, Wittayabusarakam N, Smitthisakda S
… +4 more, Sakpuwadol N, Thadanipon K, Phruttinarakorn B, Rutnin S
Am J Dermatopathol
· 2026 May · PMID 42200754
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BACKGROUND: PReferentially Expressed Antigen in MElanoma (PRAME) was introduced as an ancillary tool for confirming the diagnosis of cutaneous melanoma, including the acral lentiginous melanoma (ALM). However, its standa...BACKGROUND: PReferentially Expressed Antigen in MElanoma (PRAME) was introduced as an ancillary tool for confirming the diagnosis of cutaneous melanoma, including the acral lentiginous melanoma (ALM). However, its standardized cut-off values and prognostic performance remain inconclusive. This study assessed the diagnostic performance of PRAME immunohistochemistry (IHC) in ALM across different thresholds and explored its prognostic associations. METHODS: This retrospective cohort study reviewed 90 acral melanocytic lesions, including 60 cases of acral benign nevi and 30 cases of primary ALM. PRAME immunohistochemistry was performed on the biopsy specimens. Sensitivity and specificity were calculated at varying cut-offs. The optimal threshold was applied to link PRAME expression with the outcome and features of ALM. RESULTS: A PRAME staining threshold of 50% (score ≥3) provided the optimum cut-off for differentiating ALM, with a high specificity of 98.3% and sensitivity of 53.3%. Positive PRAME was significantly associated with higher TNM stages (ordinal odds ratio [95% confidence interval], 13.11 [2.55-67.27]) and higher rates of recurrence (hazard ratio, 6.62 [1.42-30.94]) but not with any unfavorable histopathological features or mortality. CONCLUSION: PRAME can be used as an adjunctive diagnostic tool to differentiate malignant from benign acral melanocytic lesions. It may serve as a prognostic marker for poor ALM outcomes.
Kamyab Hesari K, Saber M, Montazeri S
… +1 more, Tavakolian H
Am J Dermatopathol
· 2026 May · PMID 42173808
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Tractional alopecia is a form of hair loss caused by prolonged tension on hair follicles, typically resulting from tight hairstyles. Although histopathological features of TA have been described, differentiation from oth...Tractional alopecia is a form of hair loss caused by prolonged tension on hair follicles, typically resulting from tight hairstyles. Although histopathological features of TA have been described, differentiation from other alopecias remains challenging. In this case series, we report a novel histopathological finding (Kamyab sign) characterized by the extrusion of sebaceous glands through the follicular infundibulum onto the skin surface.
Hatton LA, Rumancik BE, Fritz M
… +4 more, Honaker EC, Green AR, Umphress BA, Newton EM
Am J Dermatopathol
· 2026 May · PMID 42167909
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We present a case of graft-versus-host disease (GVHD)-like erythroderma related to thymoma-associated multiorgan autoimmunity (TAMA), a rare paraneoplastic syndrome. A 45-year-old woman with a history of a recent thymoma...We present a case of graft-versus-host disease (GVHD)-like erythroderma related to thymoma-associated multiorgan autoimmunity (TAMA), a rare paraneoplastic syndrome. A 45-year-old woman with a history of a recent thymoma resection was admitted to the intensive care unit for erythroderma. The erythroderma had progressed over 6 months from a scaling, pruritic rash on bilateral forearms despite treatment with topical corticosteroids. Dermatologic evaluation showed scaly, hyperkeratotic plaques covering greater than 90% of total body surface area. Biopsy taken during admission showed epidermal verrucous acanthosis with parakeratosis and interface vacuolar change, and necrotic keratinocytes within the epidermis accompanied by superficial dermal lymphocytes with foci of exocytosis and dermal pigment incontinence with few eosinophils. Pathological findings and clinical correlation led to the diagnosis of GVHD-like erythroderma related to TAMA. She responded well to cyclosporine and was switched to tacrolimus before discharge. Punch biopsy after several months of treatment with tacrolimus showed improvement with milder interface dermatitis and reduction in necrotic keratinocytes. There is no standard treatment regimen for cutaneous manifestations of TAMA, and prognosis is poor in the reported cases. There are shared histopathologic findings with classic cutaneous GVHD unrelated to thymoma as well as other erythrodermic entities including drug eruptions and connective tissue diseases. The nonspecific histopathologic findings of GVHD-like erythroderma related to TAMA and the lack of established diagnostic criteria illustrate the necessity of clinicopathologic correlation for correct diagnosis when evaluating erythroderma of undifferentiated etiology.