BACKGROUND:Blastomycosis, caused by Blastomyces dermatitidis and the closely related Blastomyces gilchristii, is a systemic mycosis endemic to the Great Lakes region and the Mississippi and Ohio River valleys. Primary cutaneous blastomycosis from direct inoculation-without pulmonary or systemic involvement-is rare, with fewer than 50 cases reported in the literature. Diagnosis is particularly challenging when histochemical stains are negative and the tissue reaction pattern mimics squamous cell carcinoma. CASE PRESENTATION:A 39-year-old immunocompetent African American man presented with a progressive verrucous nasal mass after facial trauma sustained from a tree branch. Skin biopsy revealed prominent pseudoepitheliomatous hyperplasia with epidermal breakdown and granulomatous inflammation. The degree of epithelial hyperplasia with surface disruption raised initial concern for well-differentiated squamous cell carcinoma. Both Periodic Acid-Schiff (PAS) and Grocott-Gomori methenamine silver stains were initially reported as negative for fungal organisms. RESULTS:Fungal polymerase chain reaction with reflex next-generation sequencing performed on formalin-fixed paraffin-embedded tissue identified Blastomyces dermatitidis/gilchristii DNA, establishing a definitive diagnosis. Directed by this molecular result, retrospective review of the PAS stain identified a single yeast form morphologically consistent with Blastomyces, confirming that the initial organism burden was at the threshold of histochemical detection. Chest imaging and immunologic evaluation excluded pulmonary and systemic disease, supporting primary cutaneous inoculation blastomycosis. Treatment with itraconazole 200 mg twice daily resulted in significant reduction of the nasal lesion at 4-month follow-up. CONCLUSION:This case illustrates 3 diagnostic pitfalls in cutaneous blastomycosis. First, prominent pseudoepitheliomatous hyperplasia with epidermal breakdown can closely mimic well-differentiated squamous cell carcinoma, a well-recognized but underappreciated histologic confounder. Second, PAS and Grocott-Gomori methenamine silver stains may be falsely negative when organism burden is extremely low, as demonstrated by the identification of only a single yeast form on directed retrospective review. Third, fungal polymerase chain reaction with next-generation sequencing reflex from formalin-fixed paraffin-embedded tissue is a critical diagnostic tool when conventional histochemical methods and morphologic assessment are inconclusive. Primary cutaneous lastomycosis should remain in the differential diagnosis of verrucous facial lesions after penetrating trauma, even in immunocompetent patients.
ABSTRACT:Nevus sebaceous of Jadassohn (NSJ) is a congenital organoid hamartoma composed of epidermal, follicular, sebaceous, and apocrine elements that may give rise to secondary neoplasms later in life. Although most tumors arising in NSJ are benign adnexal proliferations, malignant neoplasms may occasionally develop. We report a case of a 56-year-old female patient with a long-standing lesion on the parietal scalp. Histopathologic examination revealed NSJ associated with 2 distinct malignant neoplasms: primary cutaneous apocrine carcinoma and superficial basal cell carcinoma. The diagnosis of apocrine carcinoma was established based on the morphologic findings and clinicoradiologic evaluation to exclude an internal primary malignancy. This case highlights the pluripotential nature of nevus sebaceous and underscores the importance of careful histopathologic evaluation of long-standing lesions that develop a new nodular component. This is particularly important as multiple and even malignant neoplasms may arise within a single lesion.
ABSTRACT:Melanotrichoblastoma is an exceptionally rare benign follicular neoplasm recognized by the fifth edition of the WHO classification as a heavily pigmented variant of trichoblastoma. It is characterized by a prominent proliferation of basaloid follicular germinative cells intimately colonized by active dendritic melanocytes, alongside significant stromal and intratumoral melanin deposition. Owing to its dense pigmentation and basaloid morphology, it is frequently mistaken for pigmented basal cell carcinoma, melanoma, or other pigmented adnexal tumors. We report 2 cases occurring in women aged 43 and 79 years involving the scalp and cheek, respectively. Both lesions were well-demarcated dermal neoplasms composed of basaloid nests and cords lacking epidermal connection. Architectural patterns included solid, reticulated, cribriform, and cystic areas with focal follicular keratin cyst formation. Numerous dendritic melanocytes colonized the epithelial nests, successfully verified via red chromogen SOX10 and Melan-A staining. Both tumors showed diffuse AE1/AE3 and BER-EP4 positivity, wildtype p53 expression, and highly variable CK7/CD10 staining. These cases expand the limited literature and reinforce that diagnosis depends primarily on recognition of the characteristic epithelial-melanocytic architecture, rather than a rigid reliance on single ancillary immunohistochemical markers. Awareness of this rare variant is essential to avoid diagnostic pitfalls and patient overtreatment.
Abstract: Dupilumab, an interleukin (IL)-4 and IL-13 antagonist, is a biological agent approved in 2017 for the treatment of moderate-to-severe atopic dermatitis (AD). While dupilumab has proven revolutionary in managing AD, recent reports have emerged linking its use with the subsequent development of cutaneous T-cell lymphomas (CTCLs), including mycosis fungoides (MF) and Sézary syndrome. Between 2017 and 2023, a total of 178 cases of CTCLs were reportedly associated with dupilumab therapy for AD. The most common theory for this association is “unmasking,” where patients were initially misdiagnosed with AD, failed first-line treatments and dupilumab, and later were correctly diagnosed with CTCLs. Another possibility is dupilumab might exacerbate or cause progression of preexisting CTCLs in a patient with concomitant AD. However, conversely, there is also the confounder of a false-positive diagnosis of MF after dupilumab that may overinflate the association data. It has also been reported that dupilumab can cause a reversible benign cutaneous lymphoid reaction that mimics early-stage MF both clinically and histologically, though data are sparse. As CTCL has been exclusively diagnosed in patients who received dupilumab for AD and not in patients who received dupilumab for other conditions such as asthma and since no increased incidence of noncutaneous lymphoma has been reported with dupilumab therapy, it appears unlikely that dupilumab causes or has an actual oncopathogenic effect in developing CTCL or transforming AD into lymphoma. However, this alarming observation emphasizes the need for further biological investigation in determining the mechanism by which dupilumab is associated with CTCL.
Abstract: Penile intraepithelial neoplasia is an uncommon precancerous genital lesion that may progress to invasive penile squamous cell carcinoma in the absence of proper therapeutic management. The recent trend of increasing incidence because of a heightened burden of genital human papillomavirus (HPV) infection emphasizes a need for effective diagnostic and management strategies. This article provides a clinicopathologic overview focusing on updates in tumor classification and prognostication not previously summarized. We examine changes in classification and nomenclature based on the 2022 World Health Organization guidelines and explore differences in pathogenesis and prognosis between HPV-associated and HPV-independent tumors. This article emphasizes the need for more robust molecular genetic studies to further elucidate prognostic biomarkers and explores the increasingly distinct role of immunohistochemistry in stratifying subtypes. Also, we present an illustrative case to highlight the significance of accurate diagnosis and prompt management.
ABSTRACT:Hereditary leiomyomatosis and renal cell carcinoma is a rare autosomal-dominant tumor predisposition syndrome that is caused by a germline defect in fumarate hydratase. We report a case of a 40-year-old woman who presented with multiple bilateral facial nodules arranged in a zosteriform pattern that increased in distribution over 15 years. The patient reported slight pain with eating spicy food and similar lesions in her younger sister. Biopsy was performed, and histopathological examination confirmed the diagnosis of pilar leiomyoma. An immunohistochemical study showed loss of fumarate hydratase in tumoral cells with a positive internal control, confirming the diagnosis of hereditary leiomyomatosis and renal cell carcinoma. An abdominal ultrasound was performed, revealing masses in the right and left ovaries and uterus, whereas the kidneys were free from masses. This case highlights the importance of clinical suspicion and histological evaluation for any bilateral facial nodules arranged in a zosteriform pattern, which can be part of a syndrome.
ABSTRACT:Mycosis fungoides (MF) is a cutaneous T-cell lymphoma that typically progresses slowly and has a favorable initial prognosis; however, the clinical course worsens in advanced stages. The aim of this study was to investigate the levels of programmed death-1 (PD-1), PD-L1, and PD-L2 immunoexpression in the biopsies of patients with MF. Paraffin blocks from biopsies of 82 patients diagnosed with MF between 2019 and 2025 were selected for this study. Early-phase (initial) and later-phase lesion groups, as well as CD4-positive and CD8-positive disease groups were formed based on histological findings. Immunohistochemical staining was performed for PD-1, PD-L1, and PD-L2. Positivity scores were generated for tumor cells, cells in the tumor microenvironment, and combined positivity scores. Immune scores were statistically compared across the lesion phase, CD4‑CD8 positivity status, age, and sex. Of the patients, 56 (68%) had later-phase lesions, 26 (32%) had early-phase lesions, 64 (78%) were CD4-positive, and 18 (22%) were CD8-positive. PD-1, PD-L1, and PD-L2 expression levels are higher in later-phase lesions than in early-phase lesions. The effect size was found to be small to moderate. CD4 or CD8 positivity, age, and sex did not affect PD-1, PD-L1, or PD-L2 levels. Immune checkpoint inhibitors could be beneficial in the management of MF, a disease that is difficult to treat in the advanced stages. Studies with larger patient series, in which evaluation can be performed alongside clinical staging, are needed.
ABSTRACT:Li-Fraumeni syndrome (LFS) is an inherited cancer predisposition syndrome caused by germline TP53 mutations and is associated with an increased risk of several malignancies. Although breast implant-associated anaplastic large cell lymphoma has been reported in patients with LFS, primary cutaneous anaplastic large cell lymphoma has not previously been described. We report a case of primary cutaneous anaplastic large cell lymphoma in a 64-year-old man with LFS harboring a germline TP53 p.R196* mutation who presented with a solitary ulcerated nodule on the left anterior thigh. Histopathologic examination demonstrated an ulcerated dermal infiltrate of large atypical CD30-positive T lymphocytes admixed with small lymphocytes and eosinophils. Immunophenotyping showed expression of CD3, CD2, CD4, CD30, CD43, and CD45, with weak CD5 expression and loss of CD7 and EMA. Targeted exome sequencing identified the patient's known germline TP53 mutation together with additional somatic mutations and copy number alterations, whereas whole-body positron emission tomography/computed tomography demonstrated no evidence of systemic disease. The lesion was completely excised, and radiotherapy was deferred because of the patient's underlying LFS and associated risk of radiation-induced malignancy. The patient remains disease-free 36 months after diagnosis. This case expands the spectrum of lymphoid malignancies reported in patients with LFS and highlights the importance of recognizing hereditary cancer predisposition syndromes when selecting treatment strategies for primary cutaneous lymphomas.
ABSTRACT:Facial papules (FPs) are asymptomatic, white-to-yellowish monomorphic papules that have been recently described as a clinical manifestation of frontal fibrosing alopecia. We present 9 cases of facial papules, emphasizing their subtle clinical and histopathological presentation which may be often overlooked.
ABSTRACT:Nevus sebaceous (NS) is a congenital hamartoma that may give rise to a wide spectrum of benign and malignant adnexal neoplasms, although malignant transformation is uncommon. We report a case of low- and intermediate-grade apocrine intraductal carcinoma arising in a NS of Jadassohn in a 93-year-old woman. Histopathologic examination demonstrated an intraductal apocrine neoplasm with solid and cribriform architecture, focal comedonecrosis, and an intact surrounding myoepithelial cell layer highlighted by p63 and CK5/6 immunostaining. The neoplastic cells expressed CK7, epithelial membrane antigen (EMA), and androgen receptor, whereas estrogen receptor, progesterone receptor, and HER2 were negative. The lesion was associated with basal cell carcinoma, trichoblastoma, and apocrine hidrocystoma within the same NS. The morphologic and immunophenotypic findings closely parallel those of mammary apocrine ductal carcinoma in situ, supporting the concept that analogous neoplastic transformation may occur in cutaneous apocrine ducts. This case expands the spectrum of malignant neoplasms arising in NS and contributes to the limited literature on this exceptionally rare entity. Gemini ha dicho.
Abstract: BAP1 inactivated melanocytomas are considered intermediate grade melanocytic tumors. They may have overlapping morphologic features with melanoma. Nuclear atypia, expansile growth, and mitotic activity often raise concern for the possibility of melanoma. However, there is limited information in the literature on outcomes-based diagnostic criteria that may be useful for the distinction of BAP1 inactivated melanocytomas from BAP1 inactivated melanomas. Herein, we present a series of 20 BAP1 inactivated melanomas with clinical follow-up (n = 17) and compare the genomic and morphologic features with 23 BAP1 inactivated melanocytomas. In this series, only BAP1 inactivated melanomas had ulceration, tumor necrosis, invasion of the subcutis, and mitotic activity ≥4/mm 2 . BAP1 inactivated melanomas had more pathogenic variants on average than BAP1 inactivated melanocytomas (6.6 vs. 2.4, P = 0.0001) and a higher TMB (31.2 m/Mb vs. 7.8 m/Mb, P = 0.0071). Pathogenic variants in TERT -promoter, CDKN2A , CDK4 , MYC , the SWI/SNF complex, and the PI3K-AKT pathway were only seen in BAP1 inactivated melanomas. Because BAP1 inactivated melanomas are uncommon compared with BAP1 inactivated melanocytomas, useful diagnostic criteria must have very high specificity and be rare to absent in BAP1 inactivated melanocytomas. In this study, we identified morphologic and molecular features that were strongly associated with BAP1 inactivated melanomas but not seen in BAP1 inactivated melanocytomas. Our findings may be helpful for the diagnostic assessment of challenging melanocytic tumors with BAP1 inactivation.
Abstract: Cutaneous spindle cell squamous cell carcinoma (SpSCC) is a rare variant of cutaneous squamous cell carcinoma that can clinically mimic scar change and histologically overlap with other cutaneous spindle cell neoplasms. We report a 60-year-old woman with a nonhealing ulcerated lesion arising within a longstanding childhood abdominal burn scar. Histopathology demonstrated a mitotically active dermal spindle cell tumor with pancytokeratin positivity and patchy cytokeratin 5/6 expression. This rare case highlights that spindle cell squamous cell carcinoma can arise as a late malignant transformation within longstanding burn scars decades after the initial injury. We also review key histopathologic/immunohistochemical diagnostic pitfalls and summarize practical oncologic and surgical management considerations for treating cutaneous spindle cell squamous cell carcinoma in burn scars as a high-risk cutaneous squamous cell carcinoma.
Abstract: Pilomatricoma is a benign adnexal neoplasm of matrical follicular differentiation, typically arising in the dermis or subcutis. CTNNB1 gene mutations are well recognized in pilomatricomas. Herein, we describe a rare epidermal-based pilomatricomal lesion that clinically presented with a cutaneous horn, previously reported in the literature as pilomatricomal horn. We have also identified a CTNNB1 mutation by next-generation sequencing in our case, supporting its relationship with pilomatricoma.
