Merkel cell carcinoma in situ (MCCIS), especially when unaccompanied by invasive Merkel cell carcinoma, is exceptionally rare. Most reported cases of MCCIS without invasion demonstrate the typical immunophenotype of invasive MCC, including cytokeratin 20 (CK20) positivity and thyroid transcription factor-1 (TTF-1) negativity. Here we report a case of MCCIS without invasion exhibiting a phenotype not previously reported in MCCIS: CK20 negativity with diffuse nuclear TTF-1 positivity. Arising within a seborrheic (stucco) keratosis in a 78-year-old woman, the lesion demonstrated an entirely intraepidermal proliferation of atypical cells with neuroendocrine differentiation by histology (high nuclear-to-cytoplasmic ratio, crush artifact, and nuclear molding) and immunohistochemistry (positive synaptophysin, chromogranin, neuron-specific enolase, INSM1, and SATB2). The lesion was negative for squamous markers (cytokeratin 903, cytokeratin 5/6, p40, and p63), Merkel cell polyomavirus (MCPyV/CM2B4), and neurofilament. A review of the literature identified no prior TTF-1-positive MCCIS. To our knowledge, the present case represents the first reported TTF-1-positive MCCIS and only the second reported CK20-negative MCCIS. This unusual phenotype expands the recognized immunophenotypic spectrum of MCCIS and highlights a potential diagnostic pitfall.
Granular parakeratosis (GP) is a rare disorder of keratinization characterized by the retention of keratohyalin granules within the stratum corneum. Originally described as solely involving the axillae (previously known as axillary granular parakeratosis), GP is now recognized to involve other intertriginous areas, including the inframammary folds, abdominal folds, groin, and neck. Follicular granular parakeratosis (FGP) represents an exceedingly rare variant in which the pathologic process involves the follicular infundibulum. We report a case of both follicular and inter follicular GP in a 47-year-old woman presenting with a chronic pruritic eruption on the face, anterior neck, and chest-a distribution distinct from the typical GP distribution. Histopathologic examination revealed prominent keratohyalin granules within the stratum corneum and follicular infundibulum, with multiple mounded areas of granular parakeratosis, establishing the diagnosis of FGP. To our knowledge, only three prior cases of FGP have been reported in the literature, making this a remarkably rare presentation. This case emphasizes the importance of recognizing follicular involvement in GP as a distinct clinicopathologic pattern that differs from classic GP in both location and histology.
BACKGROUND:Patients struggle to comprehend dermatopathology reports. As artificial intelligence (AI) tools become more accessible, patients may use them to interpret reports; however, optimal approaches remain unexplored. OBJECTIVE:Evaluate whether prompt-engineered AI simplification of dermatopathology reports improves factualness, completeness, and reduces potential harm compared to basic AI usage. METHODS:Survey-based study (January-April 2025) of 52 US dermatology and dermatopathology professionals (70.3% response rate). Six fictitious dermatopathology reports were simplified using: (1) Basic ChatGPT-4.0 with simple prompt and (2) Custom "DermDecoder" GPT with structured 489-word prompt. Participants rated reports on 3-point Likert scales for factualness, completeness, and potential harm, with free-text responses analyzed thematically. RESULTS:Mean ratings ranged from 1.27 to 1.63 (factualness/completeness) and 1.31-1.83 (harmfulness), indicating "Agree" to "Mostly Agree" or "Completely Harmless" to "Mostly Harmless." DermDecoder performed significantly worse for completeness in psoriasis (t = -2.79, p = 0.007) and harmfulness in molluscum contagiosum (p = 0.049) and melanoma in situ (p = 0.048). Free-text analysis revealed Basic Prompt preserved details but lacked clinical context, while DermDecoder provided generic education disconnected from pathological findings. LIMITATIONS:Fictitious reports, small sample, evolving AI capabilities, and absence of patient perspectives. CONCLUSION:Prompt engineering offered no advantage over basic AI usage in balancing professional accuracy with patient accessibility, necessitating human-in-the-loop oversight for AI-generated explanations.
We report a case of a 71-year-old female with acute myeloid leukemia (AML), treated with chemotherapy and hematopoietic stem cell transplant (HSCT), who developed a clonally related non-Langerhans cell histiocytosis (NLCH). She presented with pink papules on the mid-upper cutaneous lip and thighs 3 months following HSCT. Skin biopsies revealed a dermal proliferation of cells with eosinophilic cytoplasm. Immunohistochemistry (IHC) studies demonstrated positivity for CD68, CD163, BRAF, cyclin D1, and Factor XIIIa and negativity for CD1a, S100, MPO, and CD20. Next-generation sequencing (NGS) with a comprehensive myeloid panel revealed corresponding pathogenic mutations to her AML, including BCOR Q176fs*40, IDH1 R132C, and TP53 Y163N, and an additional BRAF V600E mutation. Additional mutations in DNMT3A and KMT2A associated with her AML were not identified. These findings supported the diagnosis of NLCH sharing a clonal origin with the patient's AML. Work up demonstrated isolated cutaneous involvement without AML relapse; therefore, the skin lesions were treated with shave excision, topical tacrolimus 0.1% ointment, and topical clobetasol 0.05% cream without further systemic treatment. The acquired BRAF V600E mutation illustrates the potential for divergent myeloid differentiation and likely explains the emergence of a clonal NLCH after successful AML treatment. Genetic analysis in NLCH can establish clonality with associated hematologic malignancies, uncover actionable mutations, and guide treatment.
We present the case of a 64-year-old patient with a previous history of atopic dermatitis and vitiligo, who presented to the dermatology clinic with persistent "bumps" on his face that appeared following treatment with upadacitinib. Examination of the skin revealed multiple skin-colored to erythematous folliculocentric papules located on the temples, lateral canthi, and eyelids. A punch biopsy demonstrated a folliculocentric process; a central follicle exhibited a robust necrotizing granulomatous infiltrate associated with hair follicle destruction. The base of the follicle displayed follicular mucinosis and a lymphocytic infiltrate with an increased CD4:CD8 ratio of 8:1, retention of CD2 and CD5, and diminished CD7 expression. Subsequent PCR analysis showed no evidence of monoclonal T-cell receptor gene rearrangement. Based on the clinical impression, the histopathological features, and ancillary test results, a diagnosis of lupus miliaris disseminatus faciei with follicular mucinosis in the context of Janus kinase (JAK) inhibitor therapy was established. Although acneiform eruptions ("JAK-ne") are known side effects of JAK inhibitor therapy, to the authors' knowledge, this novel case report is the first to describe patterns of lupus miliaris disseminatus faciei and follicular mucinosis within the spectrum of inflammatory papular facial eruptions associated with JAK inhibitor therapy.
Primary cutaneous gamma-delta T-cell lymphoma (PCGD-TCL) is a rare cytotoxic lymphoma with key oncogenic drivers in the JAK/STAT pathway. Also primarily involving the subcutaneous adipose tissue, subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is more frequently encountered in scenarios of autoimmune disorders. SPTCL shares clinicopathologic overlap with lupus panniculitis. However, the link between autoimmunity and PCGD-TCL is much less established, particularly in the setting of long-standing, immunosuppressed dermatomyositis (DM). We report two cases of PCGD-TCL arising in women with chronic anti-TIF1-γ DM following years of immunosuppressive therapy. Case 1 is a 47-year-old woman with a 19-year history of DM on azathioprine/prednisone who developed rapidly progressive, painful subcutaneous nodules. Incisional biopsy confirmed a TCR-delta+, CD8+ cytotoxic T-cell lymphoproliferative disorder (TCLPD) compatible with PCGD-TCL. She achieved complete remission following pralatrexate and subsequent allogeneic hematopoietic stem cell transplant. Case 2 is a 27-year-old woman with DM on mycophenolate/rituximab who developed subcutaneous nodules with an indolent course and some spontaneous regression. A biopsy revealed a similar panniculitic infiltrate with an atypical TCR-delta+, CD8+ phenotype. Notably, both cases were negative for high-risk JAK/STAT pathway mutations. These cases identify PCGD-TCLPD/TCL as a potential complication of chronic, immunosuppressed DM. The shared, atypical CD8+ immunophenotype and absence of canonical driver mutations suggest a distinct pathogenic mechanism possibly linked to long-term immune modulation. Unlike classic PCGD-TCL, which is characterized by an aggressive course and < 2-year median survival, the clinical courses in these two cases were variable, with one requiring transplant and the other showing indolent behavior and responsiveness to therapy.
Plaque-like CD34-positive dermal fibroma (PDF), which historically overlaps with medallion-like dermal dendrocyte hamartoma (MDDH), is a rare benign CD34-positive spindle-cell lesion with highly variable clinicopathologic descriptions. We analyzed two adult-onset cases and reviewed the published literature to determine whether reported PDF/MDDH lesions cluster into reproducible clinicopathologic patterns. Our literature review comprises 25 cases. Comparative analyses revealed marked differences in age at onset, lesion size, anatomic distribution, depth of involvement, papillary dermis sparing, subcutaneous extension, and epidermal response. One pattern was characterized by early-onset, larger plaque-like lesions on the trunk or neck, with deep dermal to subcutaneous spindle-cell proliferation and frequent epidermal atrophy (early-onset deep pattern). The second pattern was characterized by adult-onset, small papules or papuloplaques, predominantly on the extremities, featuring upper reticular dermal spindle-cell proliferation, papillary dermis sparing, elongated rete ridges, and a perpendicular-to-horizontal spindle-cell arrangement (adult-onset superficial pattern). All lesions showed diffuse CD34 positivity. Lesions currently reported under the PDF/MDDH umbrella appear to encompass two reproducible clinicopathologic patterns. Recognizing these patterns may improve diagnostic accuracy and facilitate the distinction of these lesions from dermatofibrosarcoma protuberans and other superficial CD34-positive spindle-cell proliferations.
Dermatofibrosarcoma protuberans (DFSP) is a fibroblastic malignancy characterized in most cases by COL1A1::PDGFB fusion. Rare cases exhibit alternative rearrangements involving PDGFD. Here, we describe a female patient in her third decade of life who presented with a spindle cell proliferation on the shoulder. Expression of pan-TRK and S100, together with absence of PDGFB overexpression, supported an initial impression of NTRK-rearranged spindle cell tumor. However, molecular analysis revealed PDGFD rearrangement, and re-excision demonstrated classic DFSP morphology in the residual tumor. Our findings underscore the importance of continued consideration for DFSP in tumors with focal S100 expression.
Poroid hidradenocarcinoma is a rare malignant sweat gland neoplasm. Although primary nodal hidradenoma has been reported, primary nodal poroid hidradenocarcinoma has not been described. We report a case of a 56-year-old man presenting with a nontender 5.5 cm mass within the axillary lymph node, and no identifiable primary cutaneous lesion on clinical examination or imaging. Histopathologic examination of the axillary lymph node dissection revealed involvement of 1 of 42 lymph nodes by a multinodular, solid and cystic neoplasm composed of poroid and cuticular cells with ductal differentiation, consistent with a background poroid hidradenoma. There was an abrupt transition to malignant areas with marked cytologic atypia, nuclear pleomorphism, increased mitotic activity, elevated Ki-67 proliferation index and necrosis, supporting the diagnosis of poroid hidradenocarcinoma. Tumor cells were positive for CK5 and CK7. Molecular analysis identified a YAP1::NUTM1 fusion and oncogenic mutations in EGFR exon 20 and FBXW7. At 30 months of follow-up after axillary lymph node dissection and chemoradiation, there was no evidence of disease progression. This case represents the first report of primary nodal poroid hidradenocarcinoma, expanding its clinicopathologic spectrum. Awareness of this entity is important to avoid misdiagnosis as metastatic carcinoma and to prevent potential overtreatment.
BACKGROUND:Primary cutaneous follicular helper T-cell lymphoma (pcTFH-L) is a rare, poorly characterized entity. We present six new cases to elucidate its clinicopathological features. METHODS:We retrospectively analyzed the clinical, histomorphological, and immunohistochemical features (TFH markers: PD-1, CXCL13, BCL-6, CD10, ICOS), EBV status, and T-cell receptor clonality of six pcTFH-L cases, comparing findings with 48 previously reported cases. RESULTS:The cohort (five males, one female; median age 66.5 years, range 42-75 years) presented with localized skin lesions without B symptoms or lymphadenopathy. All cases showed dermal/subcutaneous infiltration by atypical lymphocytes without epidermotropism (nodular pattern in 4 cases, diffuse pattern in 2 cases). Prominent high endothelial venules (HEVs) were exhibited in 4/6 cases. Neoplastic cells in all cases expressed CD4 and at least three TFH markers, with PD-1 (6/6), ICOS (6/6), and CXCL13 (6/6) being the most sensitive. CD21-positive follicular dendritic cell (FDC) networks were observed in 4 of 6 cases. Epstein-Barr virus-encoded RNA (EBER) was positive in 4 of 6 cases, and clonal T-cell receptor (TCR) gene rearrangements were detected in all 6 cases tested. Treatments varied from none to combination chemotherapy, with outcomes ranging from stable disease to complete remission; one patient died of heart failure, and another died at 20 months despite treatment. CONCLUSIONS:This case series reinforces pcTFH-L as a distinct cutaneous lymphoma with a characteristic immunophenotype and microenvironment. The consistent expression of multiple TFH markers, particularly PD-1, ICOS, and CXCL13, is essential for accurate diagnosis and differentiation from other cutaneous T-cell lymphoproliferative disorders. The clinical course appears heterogeneous, with some cases showing indolent behavior while others may have more aggressive outcomes.
Miliaria profunda is due to duct obstruction and rupture below the epidermis, with dermal sweat leakage associated and a variable inflammatory reaction. A rare but distinct presentation of miliaria profunda in infants is named giant centrifugal miliaria profunda (GCMP), showing centrifugal expansion of large, annular plaques. On histology, GCMP shows hyperkeratosis with ortho- and parakeratosis, and acanthosis with foci of intercellular edema. Acrosyringia are distended with obstruction by eosinophilic plugs of ortho-parakeratotic material. Dermal ducts appear dilated and show squamous metaplasia. A periductal and peri-eccrine variable inflammatory infiltrate contains neutrophils and often granulomatous inflammation is identified. We report two cases of GCMP, one of them associated with an MAP2K1 germinal RASopathy.
BACKGROUND:To investigate the clinicopathological features, CD34 heterogeneity, diagnostic value of molecular detection, and targeted therapy in recurrent or fibrosarcomatous dermatofibrosarcoma protuberans (DFSP) with sarcomatous transformation showing unusual morphology. METHODS:Three molecularly confirmed cases were analyzed and integrated with seven published cases. RESULTS:The 10 patients (6 females, 4 males; age: 27-62 years) showed a broad morphological spectrum (e.g., undifferentiated pleomorphic sarcoma-like, myxofibrosarcoma-like). CD34 expression was diffusely positive (6 cases), partially positive (1), or completely negative (3). Complete CD34 loss is a well-documented phenomenon in fibrosarcomatous DFSP. All cases harbored COL1A1-PDGFB fusion or PDGFB rearrangement. Treatments included surgery, radiotherapy, and imatinib. Follow-up revealed high risks of local recurrence and distant metastasis. Of the two imatinib-treated patients, one responded, the other was resistant. CONCLUSIONS:Recurrent or fibrosarcomatous DFSP with sarcomatous transformation can exhibit areas of unusual morphology and loss of CD34 expression, which may create significant diagnostic difficulty. Molecular detection of the COL1A1-PDGFB fusion remains the gold standard, as all cases retained the fusion despite morphological or immunophenotypic heterogeneity. Routine molecular testing is recommended for atypical cases to confirm diagnosis and guide targeted therapy.
Part I of our three-part series outlines the essential technical and operational components required for successful digital pathology implementation including hardware, software, and IT infrastructure. It reviews the rationale for digitization, highlighting improvements in workflow efficiency, diagnostic collaboration, and preparedness for computational applications. Key components of Whole Slide Imaging (WSI) systems are discussed, including practical considerations for scanner selection, scanning modalities, and performance trade-offs relevant to dermatopathology. The article also examines image compression strategies and pyramid image representation, with attention to balancing image quality and storage efficiency. Finally, we review DICOM standards and storage infrastructure options, including cloud, on-premises, and hybrid models, and associated network bandwidth requirements.
Lichen sclerosus (LS) and morphea are chronic inflammatory sclerosing dermatoses that occasionally exhibit overlap. While their coexistence within the same lesion is increasingly recognized, nodular presentations remain exceptionally rare. We report a 50-year-old woman with a strikingly distinctive presentation of a solitary, well-circumscribed, exophytic nodule on the left posterior thigh, characterized by an ivory-colored peripheral rim, and an erythematous central zone. Histopathological examination revealed features of both lichen sclerosus (epidermal atrophy, basal vacuolar alteration, and homogenized upper dermal collagen with a subjacent band-like lymphocytic infiltrate) and keloidal morphea (deep dermal sclerosis with keloidal collagen fibers extending into subcutaneous septa, entrapped adnexal structures, and lymphoplasmacytic infiltrate). The exophytic nodular morphology with keloidal features expands the known clinical spectrum of LS-morphea overlap. Recognition of this unusual variant may prevent diagnostic confusion with other nodular dermal proliferations.
The coexistence of nonmelanoma skin cancers and B-cell lymphoproliferative disorders represents a significant diagnostic challenge. Although peritumoral lymphoid infiltrates are frequently interpreted as reactive, they may occasionally correspond to underlying or previously unrecognized lymphoproliferative disorders, with relevant clinical implications. We report three diagnostically challenging cases of epithelial skin cancers associated with unusual B-cell lymphoproliferative disorders, including composite lymphomas and previously unreported associations. These cases highlight the broad spectrum of B-cell lymphoproliferative conditions that may coexist with epithelial skin malignancies and underscore the importance of meticulous morphological assessment, comprehensive immunophenotypic characterization, and careful clinicopathological correlation. Awareness of this potential association is crucial to avoid misclassification of neoplastic lymphoid infiltrates as reactive processes and to ensure appropriate hematological work-up and optimal patient management.
Cutaneous oxalosis is an uncommon manifestation of primary hyperoxalosis, which can often resemble other cutaneous manifestations of end stage renal disease (ESRD), particularly calciphylaxis. We report the case of a 46 year old female with primary hyperoxaluria type one (PH1) believed to be well-controlled on lumasiran, a small interfering ribonucleic acid therapy, which targets the mRNA responsible for producing hydroxyacid oxidase 1 (HAO1) and through reduction of this enzyme, decreases the hepatic overproduction of oxalate. The patient presented for dermatologic evaluation of presumed calciphylaxis. Repeated skin biopsies, however, confirmed cutaneous oxalosis despite perceived stable metabolic control with lumasiran. This case highlights the complexities and challenges in the diagnosis of cutaneous manifestations of chronic kidney disease and emphasizes the importance of histopathologic evaluation, even if the patient's primary hyperoxaluria is believed to be well-controlled.
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive hematopoietic neoplasm of immature plasmacytoid dendritic cells. Before the cell of origin was elucidated, it was previously termed "CD4+/CD56+ hematodermic neoplasm," "agranular CD4+ natural killer (NK) cell leukemia," "blastic NK-cell lymphoma," and "blastic NK leukemia/lymphoma." While there is a high frequency of concurrent cutaneous and bone marrow involvement at presentation, some cases may present with disease localized to the skin. Since the most common site of involvement is the skin, the diagnosis is generally made via skin biopsy. However, limited experience with this rare entity may lead to diagnostic delay. The histopathologic, immunohistochemical, and molecular findings as well as the current diagnostic criteria for BPDCN are reviewed. In addition, the differential diagnosis with acute myeloid leukemia with CD4/CD56/CD123 positivity and reactive plasmacytoid dendritic cell hyperplasia is discussed.
We report a case of atypical Grover disease occurring in association with Merkel cell carcinoma (MCC). A 63-year-old man presented with a four-month history of generalized pruritic papules. Skin biopsy demonstrated focal intraepidermal acantholysis with dyskeratosis and patchy vacuolar interface change, with negative direct immunofluorescence. Given the widespread eruption, systemic symptoms, and histopathologic findings, an atypical paraneoplastic variant of Grover disease was suspected. Four months later, the patient was diagnosed with metastatic MCC. His dermatologic disease improved with dupilumab and remained controlled during oncologic treatment. To our knowledge, this represents a previously unreported association between atypical Grover disease and MCC and raises the possibility of a paraneoplastic presentation.
