Kodaka E, Iino S, Kishimoto C
… +7 more, Matsuda-Okazaki T, Oyama N, Muramoto A, Higuchi S, Imamura Y, Katsuo K, Hasegawa M
Am J Dermatopathol
· 2026 Jun · PMID 42379634
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Basal cell carcinoma rarely coexists with malignant mesenchymal component(s), termed as basal cell carcinosarcoma (BCCS). BCCS often comprises an osteosarcomatous change, which considerably varies in the histological ext...Basal cell carcinoma rarely coexists with malignant mesenchymal component(s), termed as basal cell carcinosarcoma (BCCS). BCCS often comprises an osteosarcomatous change, which considerably varies in the histological extent among reported cases. Owing to its rarity and morphological heterogeneity, the disease may be underrecognized and pose accurate diagnosis and treatment approaches. In this study, we present a case of BCCS with a focal osteosarcomatous component in a 91-year-old woman with a rapidly enlarging solitary tumor on the left cheek. Histopathological examination revealed a biphasic tumor composed of conventional basal cell carcinoma and a high-grade sarcomatous component, both of which were intermingled gradually in the transitional zone. Limited portions of the sarcomatous component contained atypical spindle-to oval-shaped cells and osteoclast-like multinucleated giant cells surrounded by an osteoid matrix. Immunohistochemically, these cells were positive for an osteoblastic marker SATB2 and an osteoclast-associated marker tartrate-resistant acid phosphatase, respectively, but negative for epithelial markers AE1/AE3 and BerEP4. These findings supported a diagnosis of BCCS with an osteosarcomatous component. To the best of our knowledge, literature review identified only 21 similar cases thus far reported, but no previous reports have used a combined use of SATB2 and tartrate-resistant acid phosphatase immunostaining to substantiate the osteosarcomatous focus in cutaneous carcinosarcoma. Our case may highlight the potential diagnostic value of these 2 markers in distinguishing the true osteosarcomatous components from mimicking elements such as dystrophic calcification or hyalinized collagen deposition, but also in detecting a subtle osteosarcomatous component in carcinosarcoma.
Am J Dermatopathol
· 2026 Jun · PMID 42358060
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Histopathological examination using hematoxylin and eosin (H&E)-stained tissue is sufficient for diagnosing most melanocytic neoplasms as benign or malignant; however, diagnostic tools such as PRAME (preferentially expre...Histopathological examination using hematoxylin and eosin (H&E)-stained tissue is sufficient for diagnosing most melanocytic neoplasms as benign or malignant; however, diagnostic tools such as PRAME (preferentially expressed antigen in melanoma) immunohistochemistry (IHC) and the 23-gene expression profile (23-GEP) test can aid in the analysis of histopathologically ambiguous lesions, which can be referred to as diagnostically challenging, equivocal, indeterminate, or uncertain. When compared with the gold standard of H&E diagnosis by a dermatopathologist, PRAME IHC showed 83.2% sensitivity and 99.3% specificity in an initial validation cohort and 23-GEP showed 91.5% sensitivity and 92.7% specificity in an independent validation cohort. In addition, 23-GEP has been evaluated in 3 studies with patients with known outcomes (eg, metastasis) and has reported metrics of 90.4%-96.3% sensitivity and 87.3%-96.2% specificity in distinguishing benign versus malignant melanocytic neoplasms. In this study, we present the utility of the 23-GEP test within 8 equivocal cases with various PRAME IHC staining patterns. Cases underwent histopathological review and received at least 4 and up to 5 diagnoses each. In samples where PRAME IHC is inconclusive, conflicting, or ambiguous regarding a final diagnosis, the 23-GEP can provide additional diagnostic information to upgrade or downgrade the overall malignant potential of the lesion in question.
McFadden JR, Htoo A, Chaudhari AS
… +4 more, Stevanovic M, Tsongalis GJ, Hughes EG, Sriharan A
Am J Dermatopathol
· 2026 Jun · PMID 42358058
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Melanoma progression is generally associated with a stepwise increase in genomic complexity. Although the copy number variations (CNVs) known to occur in melanoma are well characterized, the order in which they accumulat...Melanoma progression is generally associated with a stepwise increase in genomic complexity. Although the copy number variations (CNVs) known to occur in melanoma are well characterized, the order in which they accumulate during melanomagenesis remains incompletely understood. To explore this, we used droplet digital polymerase chain reaction to calculate absolute copy numbers of RREB1 and CDKN2A, the most commonly amplified and deleted genes in melanoma, in 51 formalin-fixed, paraffin-embedded melanomas. Each sample also underwent chromosomal microarray analysis to determine its CNV burden, which we graded according to the number of the following melanoma-associated CNVs present: RREB1 gain, CDKN2A loss, MYC gain, and MYB loss. In this pilot study, increasing CNV burden was associated with a gradual increase in average RREB1 copy number: from 2.00 in CNV-negative melanomas to 2.68 in melanomas with isolated RREB1 gain; 2.75 in melanomas with RREB1 gain and CDKN2A loss; 2.93 in melanomas with RREB1 gain and MYC gain; and 3.23 in melanomas with RREB1 gain, CDKN2A loss, and MYC gain (F = 10.43, P < 0.001). A parallel trend was observed for average CDKN2A copy number, which decreased progressively with increasing CNV burden: from 2.02 in CNV-negative melanomas to 1.33 in melanomas with isolated CDKN2A loss; 1.15 in melanomas with CDKN2A loss and MYC gain; and 0.53 in melanomas with CDKN2A loss and MYB loss (F = 12.01, P < 0.001). These findings support a potential model of stepwise CNV accumulation in melanoma: early RREB1 gain and/or CDKN2A loss, followed by MYC gain, and ultimately MYB loss.
Am J Dermatopathol
· 2026 Jun · PMID 42358055
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There are conflicting statements in the literature about the existence of Montgomery tubercles in the male areola. We wished to determine whether the male breast contains Montgomery tubercles and to determine additional...There are conflicting statements in the literature about the existence of Montgomery tubercles in the male areola. We wished to determine whether the male breast contains Montgomery tubercles and to determine additional pathology, if any, in the male areola. Serial sections from areola of paraffin blocks from six retrospective and five prospective cases of male breast carcinoma were evaluated. Only hematoxylin-stained and eosin-stained sections were studied. There were definite Montgomery tubercles in two cases and putative Montgomery tubercles in two other cases, among the 11 cases (age range, 42-85 years) studied. Demodex mites (n = 8) and dermatophytes (n = 3) were noted in the areola. Toker cells were absent, Paget disease was present (n = 1), and Pagetoid dyskeratosis was present in 5 cases. We conclude that Montgomery tubercles are present in the male areola. Demodex and dermatophytes are common commensals in the male areola. Giovanni Morgagni, Johann Roederer, Johann Meckel the Younger, William Montagna, and A. Bernard Ackerman have made scientific contributions to Montgomery tubercles of females and in other areas of pathology.
Bertlich I, Bertlich R, Arning AC
… +1 more, Bertlich M
Am J Dermatopathol
· 2026 Jun · PMID 42358054
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We report an unusual case of metastatic syringocystadenocarcinoma papilliferum in an 18-year-old man who presented with cervical lymph node metastasis initially diagnosed as dedifferentiated squamous cell carcinoma of un...We report an unusual case of metastatic syringocystadenocarcinoma papilliferum in an 18-year-old man who presented with cervical lymph node metastasis initially diagnosed as dedifferentiated squamous cell carcinoma of unknown primary. Extensive diagnostic workup failed to identify a primary tumor, until reexcision of a childhood scalp lesion revealed a deeply infiltrative adnexal neoplasm with ductal differentiation consistent with syringocystadenocarcinoma papilliferum, and comparison of the lymph node specimens with the scalp specimen showed cytological similarities. This case emphasizes that the working diagnosis should be questioned by the pathologist and the clinician when clinical characteristics do not seem to fit. It furthermore highlights the importance of the inclusion of prior pathology specimens into the pathological workup, and careful evaluation for ductal differentiation in atypical squamous cell carcinoma presentations.
Am J Dermatopathol
· 2026 Jun · PMID 42358046
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BACKGROUND: Collision tumors combining basal cell carcinoma (BCC) and melanoma are exceptionally rare, and their distinction from melanoma colonization remains controversial. CASE PRESENTATION: A 68-year-old man presente...BACKGROUND: Collision tumors combining basal cell carcinoma (BCC) and melanoma are exceptionally rare, and their distinction from melanoma colonization remains controversial. CASE PRESENTATION: A 68-year-old man presented with a persistent ulcer on the lower lip, initially believed to represent BCC. Wedge resection revealed a 2.2 cm ulcerated lesion composed of BCC with malignant melanocyte colonization. Immunohistochemical analysis confirmed the biphasic nature: the melanocytic component was positive for S100, Melan-A, SOX10, and PRAME (with p16 loss), and the epithelial component was positive for p40 and Bcl-2. The melanoma measured 7.5 mm in Breslow thickness (pT4b) with ulceration and perineural invasion, but no lymphovascular involvement. Margins were negative. A sentinel lymph node biopsy was recommended but was declined by the patient. CONCLUSION: This case illustrates the diagnostic complexity and clinical effect of BCC-melanoma collision/colonization tumors. Prognosis is dictated by the melanoma component, underscoring the need for meticulous histopathologic evaluation and immunohistochemistry in guiding patient management.
Am J Dermatopathol
· 2026 Jun · PMID 42358041
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Immunohistochemistry (IHC) is widely used in dermatopathology to support diagnostic classification, yet the reproducibility of IHC interpretation is rarely evaluated in studies of diagnostic performance. Because most IHC...Immunohistochemistry (IHC) is widely used in dermatopathology to support diagnostic classification, yet the reproducibility of IHC interpretation is rarely evaluated in studies of diagnostic performance. Because most IHC tests require visual interpretation by pathologists, variability in reader interpretation may influence reported test accuracy. We conducted a systematic review of diagnostic accuracy studies of dermatopathology IHC diagnostic biomarkers published between 2015 and 2025 to determine how frequently interobserver agreement is reported. Searches of PubMed, Embase, and Web of Science identified 1461 abstracts, of which 84 studies met inclusion criteria. Although most studies reported sensitivity and specificity, 73 of 84 (87%) did not report any measure of interobserver agreement. When reported, agreement was most commonly assessed using Cohen kappa statistic, although qualitative descriptions of concordance were also used. To integrate diagnostic accuracy with reproducibility, we explored a composite metric, the kappa-balanced score, defined as the geometric mean of balanced accuracy and Cohen kappa. Kappa-balanced score was calculable in three studies and ranged from 0.62 to 0.93. These findings indicate that interobserver agreement is substantially underreported in dermatopathology IHC studies, highlighting the need for routine reporting of reproducibility metrics in diagnostic accuracy research.
González Fernández J, García García M, Larrosa Martínez D
… +3 more, Ara Martín M, de la Fuente Meira S, Prieto Torres L
Am J Dermatopathol
· 2026 May · PMID 42358039
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Mutations in KRT5, POFUT1, POGLUT1, and PSENEN define four genetic subtypes of Dowling-Degos disease (DDD), with varied clinical and histologic expression including those previously reported as Galli-Galli disease. We re...Mutations in KRT5, POFUT1, POGLUT1, and PSENEN define four genetic subtypes of Dowling-Degos disease (DDD), with varied clinical and histologic expression including those previously reported as Galli-Galli disease. We report a case of DDD3 associated with a novel early nonsense variant in POGLUT1 (c.12G>A; p.Trp4*), representing, to the best of our knowledge, the first documented case in Spain. A 55-year-old man presented with recurrent pruritic erythematous scaly papules on the trunk and hyperkeratotic brown papules on the cervical and thoracic regions. Direct microscopic examination of scales from erythematous lesions revealed yeast cells and short hyphae compatible with Malassezia sp. Initial histopathologic evaluation of a pigmented papule was interpreted as simple lentigo. Subsequent biopsy demonstrated elongated rete ridges and focal suprabasal acantholysis without dyskeratosis, raising suspicion for DDD. Whole-exome sequencing identified a heterozygous nonsense variant in POGLUT1, confirming the diagnosis of DDD3. Previous studies have shown that diffuse cytokeratin 5 (CK5) expression throughout all epidermal layers may support the diagnosis of DDD3. This case highlights diagnostic pitfalls related to subtle and focal acantholysis, emphasizes the importance of clinicopathologic correlation and serial sectioning.
BACKGROUND: Bowen's disease (BD), or squamous cell carcinoma in situ, is a common cutaneous neoplasm with an incompletely understood etiopathogenesis often linked to human papillomavirus (HPV). While the classic presenta...BACKGROUND: Bowen's disease (BD), or squamous cell carcinoma in situ, is a common cutaneous neoplasm with an incompletely understood etiopathogenesis often linked to human papillomavirus (HPV). While the classic presentation is an erythematous macule, rare variants such as verrucous BD exist and can pose significant diagnostic challenges. CASE REPORT: We present the case of a 91-year-old woman with a long-standing, 25 mm yellowish, verrucous lesion on her left leg. Clinically, the lesion was highly suggestive of verrucous carcinoma, leading to surgical excision. Histopathological examination revealed an exophytic verrucous tumor without dermal invasion. High magnification showed full-thickness architectural disarray, cytological atypia, and pagetoid spread. Immunohistochemical studies demonstrated strong, diffuse positivity for p16 and Ki67 across all epidermal layers, while p53 was negative. These findings confirmed a diagnosis of the verrucous variant of BD. DISCUSSION: Verrucous BD is a rare subtype that is easily misdiagnosed as verrucous carcinoma, an infiltrative neoplasm generally considered unrelated to HPV. Differentiation is critical, as verrucous BD often shows a strong association with high-risk HPV types. Immunohistochemistry serves as a vital tool; intense p16 expression is a highly suggestive marker for HPV-related BD, whereas verrucous carcinoma typically shows low or absent p16 expression. CONCLUSION: This case highlights the importance of considering verrucous BD in the differential diagnosis of exophytic, hyperkeratotic lesions. Accurate identification through histopathology and immunohistochemical markers like p16 is essential to distinguish this in situ variant from more aggressive, invasive entities like verrucous carcinoma.
Am J Dermatopathol
· 2026 May · PMID 42358036
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Eccrine syringofibroadenoma (ESFA) is an uncommon benign adnexal neoplasm characterized by eccrine ductal differentiation and a distinctive reticulated architectural pattern. The nonfamilial unilateral linear subtype is...Eccrine syringofibroadenoma (ESFA) is an uncommon benign adnexal neoplasm characterized by eccrine ductal differentiation and a distinctive reticulated architectural pattern. The nonfamilial unilateral linear subtype is exceedingly rare and may pose diagnostic difficulty, particularly in acral locations. We describe a long-standing unilateral linear plantar lesion in a middle-aged woman. Histopathological examination revealed anastomosing epithelial cords extending from the epidermis into a fibrovascular stroma, with associated eccrine duct-like structures, consistent with ESFA. Recognition of these characteristic features is essential to distinguish ESFA from other reactive, infectious, and neoplastic eccrine proliferations encountered in dermatopathology practice.
Lenskaya V, Liu A, Nagarajan P
… +3 more, Aung PP, Curry JL, Torres-Cabala CA
Am J Dermatopathol
· 2026 Jun · PMID 42358034
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Rothia mucilaginosa has emerged as an important opportunistic pathogen, challenging the traditional view of this organism as a harmless oral commensal. Invasive infections are increasingly recognized in immunocompromised...Rothia mucilaginosa has emerged as an important opportunistic pathogen, challenging the traditional view of this organism as a harmless oral commensal. Invasive infections are increasingly recognized in immunocompromised patients, particularly those with hematolymphoid malignancies, solid organ, and stem cell transplants, and neutropenia. Cutaneous involvement, however, remains underrepresented and remains a diagnostic challenge in view of its ambiguous morphology in tissue sections and nonspecific special stains results. We report 3 cases of suspected or confirmed cutaneous involvement by R. mucilaginosa in immunocompromised patients with hematolymphoid malignancies and profound neutropenia. In all cases, the organisms appeared as small, round eosinophilic coccoid structures predominantly within the vascular spaces and forming aggregates within the papillary dermis. The organisms were positive on periodic acid-Schiff, Grocott methenamine silver, and gram stains, with some variable stain reactivity. One case demonstrated culture-proven R. mucilaginosa bacteremia with a fatal clinical course in the setting of systemic sepsis. In addition, we present a pitfall case in which platelet aggregates closely mimicked morphology of R. mucilaginosa aggregates, creating a potential diagnostic trap. In this context, CD61 immunohistochemistry was helpful in distinguishing platelet aggregates, which showed strong positivity, from R. mucilaginosa organisms, which were negative. Our findings highlight the importance of considering R. mucilaginosa in the differential diagnosis of cutaneous infections in immunocompromised patients and emphasize potential histopathologic pitfall. Awareness of the R. mucilaginosa morphologic features, its nonspecific findings on special stains and the use of adjunct immunohistochemical studies may help avoid misinterpretation and facilitate accurate diagnosis.
Am J Dermatopathol
· 2026 Jun · PMID 42358028
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Lipomatosis of nerve is a rare, nonhereditary congenital overgrowth disorder involving fibroadipose tissue proliferation along nerve territories, most commonly the median and plantar nerves. We report a case of a 35-year...Lipomatosis of nerve is a rare, nonhereditary congenital overgrowth disorder involving fibroadipose tissue proliferation along nerve territories, most commonly the median and plantar nerves. We report a case of a 35-year-old man presenting with slowly progressive enlargement of the thumb and index finger since childhood, associated with increasing discomfort. Imaging demonstrated nonencapsulated fatty overgrowth with digital nerve involvement and associated bony hypertrophy. Surgical management included right thumb debulking and distal phalanx amputation of the index finger. Histopathologic examination confirmed infiltration of epineural and perineurial structures by adipose and fibrous tissue, consistent with lipomatosis of the median nerve. Postoperatively, the patient exhibited diminished thumb sensation with a preserved range of motion. This case highlights the diagnostic role of imaging, along with radiologic-pathologic correlation and the potential for postoperative sensory loss because of unavoidable excision of involved nerve tissue.
Tolentino ES, Dos Santos MC, Moreschi ARC
… +3 more, de Lima HG, de Miranda FV, Cardoso CL
Am J Dermatopathol
· 2026 May · PMID 42358025
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Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is a low-grade B-cell lymphoma, whose primary manifestation in the oral cavity is exceedingly rare. Owing to its nonspecific clinical...Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is a low-grade B-cell lymphoma, whose primary manifestation in the oral cavity is exceedingly rare. Owing to its nonspecific clinical presentation and histopathological overlap with benign inflammatory or reactive lesions, the diagnosis of MALT lymphoma can be challenging. We report the case of a middle-aged patient presenting with a slow-growing, asymptomatic oral lesion initially suspected to be an oral lipoma. Histopathological examination, complemented by immunohistochemical analysis, confirmed the diagnosis of primary oral MALT lymphoma. This report highlights the diagnostic challenges associated with oral lymphoid proliferations and underscores the critical importance of clinicopathological correlation for achieving an accurate diagnosis and ensuring appropriate management.
Aksu A, Altınel D, Arslan S
… +5 more, Aktaran A, Cetinkaya PO, Kurt BÖ, Kaya HE, Altunay İ
Am J Dermatopathol
· 2026 May · PMID 42358024
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Enhancer of Zeste Homolog 2 (EZH2), the catalytic subunit of the Polycomb Repressive Complex 2 (PRC2), mediates histone H3 lysine 27 trimethylation (H3K27me3) and plays an important role in epigenetic transcriptional rep...Enhancer of Zeste Homolog 2 (EZH2), the catalytic subunit of the Polycomb Repressive Complex 2 (PRC2), mediates histone H3 lysine 27 trimethylation (H3K27me3) and plays an important role in epigenetic transcriptional repression and oncogenesis. Although EZH2 mutations are well characterized in B-cell lymphomas, its role in cutaneous T-cell lymphomas, including mycosis fungoides (MF), remains incompletely understood. The aim of this study was to evaluate EZH2 expression in MF using immunohistochemistry and to investigate its association with clinicopathologic parameters and proliferative activity. A total of 46 patients with MF were retrospectively analyzed. The cohort comprised 41 patients with early-stage disease (IA-IB) and 5 patients with more advanced disease manifestations (plaque and tumor lesions, including stage IIB cases). Nuclear EZH2 expression was semiquantitatively scored, and the Ki-67 proliferation index was assessed. Associations between EZH2 expression and clinicopathologic variables were analyzed using nonparametric statistical tests, including the Kruskal-Wallis and Spearman correlation tests. EZH2 expression increased progressively with advancing disease stage and lesion morphology (P < 0.05). A significant positive correlation was observed between EZH2 expression and disease stage (r = 0.342; P = 0.02), and with the Ki-67 proliferation index (r = 0.575; P < 0.001). EZH2 expression showed no significant association with serum lactate dehydrogenase levels, β2-microglobulin levels, age, sex, or disease duration. The relatively small sample size, particularly the limited number of advanced-stage cases, and the retrospective design represent study limitations. These findings demonstrate that EZH2 expression parallels disease progression and proliferative activity in MF and suggest that EZH2 immunohistochemistry may serve as a useful adjunct marker reflecting biological disease activity in routine dermatopathologic evaluation.
Heibel HD, Oprea Y, Zengin HB
… +4 more, Chan CX, Cooper DL, Amin B, McLellan BN
Am J Dermatopathol
· 2026 Jun · PMID 42358022
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BACKGROUND AND PURPOSE: Follicular mucinosis is characterized by deposits of mucin in the sebaceous gland and outer root sheath of hair follicles. The diagnosis may occur without another cutaneous disease ("idiopathic" f...BACKGROUND AND PURPOSE: Follicular mucinosis is characterized by deposits of mucin in the sebaceous gland and outer root sheath of hair follicles. The diagnosis may occur without another cutaneous disease ("idiopathic" follicular mucinosis) or in association with hematologic malignancies, most often cutaneous T-cell lymphoma, and other skin conditions. PATIENT: We present a case of follicular mucinosis occurring in an African male with adult T-cell leukemia-lymphoma. RESULTS AND INTERPRETATION: Four cases of follicular mucinosis in the setting of adult T-cell leukemia-lymphoma have been reported previously in the literature. It is important to consider that not all lymphoma related follicular mucinosis is associated with cutaneous T-cell lymphoma.
Am J Dermatopathol
· 2026 May · PMID 42358021
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Loncastuximab tesirine (LT) is a CD19-directed antibody-drug conjugate approved for the treatment of relapsed or refractory diffuse large B-cell lymphoma. We report a case of a persistent, diffuse telangiectatic eruption...Loncastuximab tesirine (LT) is a CD19-directed antibody-drug conjugate approved for the treatment of relapsed or refractory diffuse large B-cell lymphoma. We report a case of a persistent, diffuse telangiectatic eruption that developed shortly after initiation of LT. Histopathologic examination revealed mild epidermal thinning with superficial ectatic vessels, large conspicuous fibroblasts, solar elastosis, and scattered dermal melanophages. This case highlights a distinctive, minimally inflammatory, vascular-predominant reaction pattern associated with LT. This morphology has been only recently recognized as a potential adverse effect of antibody-drug conjugate medications, with very few published literature on the subject. Because the use of antibody-drug conjugates continues to expand, recognition of this pattern is important, particularly given its persistence even after therapy cessation and limited response to corticosteroid treatment.
Am J Dermatopathol
· 2026 May · PMID 42358019
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Given clear cell acanthoma's overlapping similarities with psoriasis, we compared the presence of psoriasis and its known cardiovascular comorbidities in patients with clear cell acanthoma with patients with a control be...Given clear cell acanthoma's overlapping similarities with psoriasis, we compared the presence of psoriasis and its known cardiovascular comorbidities in patients with clear cell acanthoma with patients with a control benign skin lesion (seborrheic keratosis). We found no significant relationship between clear cell acanthoma and psoriasis.