Eyelid Eccrine Poroma: A Case Report and Literature Review.

Eccrine poroma is a rare benign adnexal tumor arising from intradermal cells of eccrine sweat ducts. At least two-thirds of eccrine poromas present on the extremities, most commonly on the palms and soles. They are scarcely found on the face; to date, only 11 cases of eyelid poromas have been reported in PubMed. Biopsy excision with a free margin is necessary to distinguish it from malignant lesions and avoid recurrence with possible transformation to porocarcinoma. We present the case of a 23-year-old male with a histopathological confirmation of poroma using staining with hematoxylin-eosin on the eyelid, previously clinically diagnosed with molluscum contagiosum. After four years, he has not experienced a recurrence.

A Misdiagnosed Familiar Brooke-Spiegler Syndrome: Case Report and Review of the Literature.

Aim of the report: Brooke-Spiegler syndrome (BSS) is a rare autosomal dominant disease characterized by the growth of cylindromas, spiradenomas, trichoepitheliomas, or their combination. These neoplasms usually begin in the second decade and progressively increase in number and size over the years. Diagnosis necessitates consideration of family history, clinical examination, histological findings, and genetic analysis. The aim of this paper is to explore the clinical overlap between Brooke-Spiegler syndrome (BSS) and neurofibromatosis type 1 (NF1). We aim to highlight the challenges associated with their differential diagnosis and emphasize the lack of standardized diagnostic criteria and treatment approaches. Case presentation: Hereby, we introduce the case of a 28-year-old male referred for suspicion of neurofibromatosis type 1 (NF1) who initially declined the recommended surgical excision for a scalp mass. After four years, he returned with larger masses of the scalp, and underwent excision of multiple masses, revealing cylindromas, spiradenomas, and spiradenocylindromas. Family history reported similar tumors in his father, who was also diagnosed with NF1 for the presence of multiple subcutaneous lesions on the scalp. Clinical overlap led to a genetic consultation, but testing for CYLD mutations yielded no significant variations. Despite this, the strong family history and consistent findings led to a revised diagnosis of Brooke-Spiegler syndrome, correcting the initial misdiagnosis of NF1 syndrome. Conclusions: Thanks to the evolving landscape of BSS research over the past two decades, its molecular underpinnings, clinical presentation, and histopathological features are now clearer. However, a thorough family history assessment is mandatory when BSS is suspected. It is our belief that a multidisciplinary approach and cooperation between specialists are essential when dealing with BSS. By sharing this case, we hope to underscore the importance of considering BSS as a differential diagnosis, especially in cases with atypical presentations or overlapping features with other syndromes like NF1.

Fusion-driven cutaneous and superficial mesenchymal and adnexal tumors-A clinicopathologic and molecular study of 15 cases, including a novel case of ACTB::ZMIZ2-rearranged adnexal carcinoma.

BACKGROUND: While the list of fusion-driven soft tissue neoplasms is expanding rapidly, their importance among cutaneous and superficial mesenchymal and adnexal neoplasms remains poorly understood. This challenge is especially evident in cases with ambiguous histopathology that are difficult to classify based on morphology. AIMS: Our goal was to investigate the benefits of next-generation sequencing in diagnosing complex cutaneous neoplasms. MATERIALS & METHODS: Departmental archives were searched for fusion-driven cutaneous neoplasms. Slides were retrieved and clinical information including follow-up was obtained. RESULTS: Fifteen cases occurred in eight female and seven male patients, with a median age of 26 years (range: 1-83) at diagnosis. Tumors involved the extremities (9), scalp (5), and head and neck (1). Predominant features included myoepithelial (5), nested spindled with clear cytoplasm (2), atypical adnexal/squamoid (2), small round blue cell (2), cellular spindled (3), and fibrohistiocytic morphology (1). Most frequently encountered fusions involved EWSR1 (6) fused to ERG (1), FLI1 (1), CREB1 (2), CREM (1), PBX3 (1), followed by PLAG1 (4) with LIFR (2), TRPS1 (1) and CHCHD7. Additional fusions encountered were YAP1::NUTM1, EML4::ALK, SS18::SSX1 (2), and a novel fusion: ACTB::ZMIZ2. Integration of histologic features and molecular findings led to final diagnoses of primary cutaneous Ewing sarcoma (2), soft tissue myoepithelioma (4), cutaneous syncytial myoepithelioma (1), cutaneous adnexal carcinoma (1), porocarcinoma (1), inflammatory myofibroblastic tumor (1), synovial sarcoma (2), clear cell sarcoma (2), and angiomatoid fibrous histiocytoma (1). DISCUSSION AND CONCLUSION: Our results show that fusion testing can be a helpful diagnostic tool, especially in cases with unusual or uncommon morphology in superficial sites. Furthermore, it can allow for the identification of potential therapeutic targets in some instances.

Primary cutaneous apocrine carcinoma: A challenging case report.

INTRODUCTION: Primary cutaneous apocrine carcinomas of the axilla represents an extremely rare entity, with <200 cases reported in the literature. It can be challenging, even almost impossible, to distinguish histologically from metastases of breast origin. We herein present the first case of an axillary cutaneous apocrine adenocarcinoma followed and treated in our institute. CASE PRESENTATION: A 58-year-old man with a history of myopathy, presented for a right axillary swelling. Physical examination revealed the presence of a 10 cm right axillary mass, no palpable adenopathy, and bilateral gynecomastia. A biopsy of the mass was performed, showing a pattern consistent with a secondary localization of mammary neoplasia. Breast and distant radiological examinations were negative. The tumor markers' levels were not raised. Therefore, the patient underwent surgery with a large excision, a right axillary lymph node dissection, covered with a pedicled pectoralis major flap. Histological and immunohistochemical examinations showed a high expression of CK7 with a negative expression of TTF1, RH, PSA, and CK20. The diagnosis of an apocrine adenocarcinoma from cutaneous origin was confirmed. CLINICAL DISCUSSION: Primary cutaneous apocrine carcinomas are a group of uncommon malignant adnexal tumors, whose diagnosis is almost impossible to confirm preoperatively. Wide, local excision with clear margins, with or without lymph node dissection is the standard treatment. CONCLUSION: This case illustrates the importance of clinico-pathological correlation of skin cancers, especially apocrine ones. Clinical particularity and careful histological analysis are used to guide the diagnostic approach.

Primary cutaneous apocrine carcinoma with RARA::NPEPPS fusion.

Gene fusions have emerged as crucial molecular drivers of oncogenesis in a subset of cutaneous adnexal neoplasms, including poroid neoplasms and hidradenomas. We present a unique case of primary cutaneous apocrine carcinoma harboring RARA::NPEPPS fusion, broadening the spectrum of fusion-associated cutaneous adnexal neoplasms. A 77-year-old African American male presented with an ulcerated thigh nodule. Histopathologically, the predominantly dermal-based adenocarcinoma exhibited papillary, micropapillary, cribriform, and solid growth patterns with central comedonecrosis, set in a fibrotic/desmoplastic stroma. Immunophenotypically, the neoplastic cells were positive for CK7, CK19, GATA3, TRPS1, HER2, CK5/6, calretinin, p63, and DPC4 (no loss), while lacking immunoreactivity for CK20, CDX2, TTF1, napsin-A, PAX8, arginase-1, adipophilin, NKX3.1, uroplakin II, and D2-40. The immunoprofile and clinical and radiographic absence of any internal malignancy, including breast carcinoma, except for multiple lymphadenopathy, supported the diagnosis of primary cutaneous apocrine carcinoma. Next-generation sequencing unveiled the novel RARA::NPEPPS fusion, concurrent ERBB2 amplification, and multiple somatic mutations involving TP53, CDKN2A, BRCA2, PIK3CA, PIK3R1, and others. The patient developed widespread metastases within a year after the initial diagnosis, indicating the tumor's aggressive behavior. This novel fusion, unprecedented in any human malignancies including primary cutaneous adnexal carcinomas, may suggest a potential new subtype within primary cutaneous adnexal carcinoma.

TRPS1 expression in non-melanocytic cutaneous neoplasms: an immunohistochemical analysis of 200 cases.

BACKGROUND: Although trichorhinophalangeal syndrome type 1 (TRPS1) was initially thought to be highly sensitive and specific for carcinomas and mesenchymal tumors of mammary origin, more recent data suggest its expression is not limited to breast neoplasms but also can be seen in other cutaneous neoplasms, such as extramammary Paget disease and squamous cell carcinoma (SCC) in situ. METHODS: Two-hundred cases of non-melanocytic cutaneous neoplasm, including basal cell carcinomas (BCCs) (n = 41), SCCs (n = 35), Merkel cell carcinomas (MCCs) (n = 25), and adnexal neoplasms (n = 99), were tested for TRPS1 expression using a monoclonal anti- TRPS1 rabbit anti-human antibody. RESULTS: TRPS1 expression was present in almost all cases of SCC (94%), with a median H-score of 200, while it was either absent or only focally present in most BCCs (90%), with a median H-score of 5. The difference between BCCs and SCCs in H-score was significant (p < .001). All MCCs (100%) lacked TRPS1 expression. TRPS1 expression was frequently seen in most adnexal neoplasms, benign and malignant, in variable intensity and proportion but was consistently absent in apocrine carcinomas. All endocrine mucin-producing sweat gland carcinomas (EMPSGCs) (100%, 6/6) showed diffuse and strong TRPS1 immunoreactivity, with a median H-score of 300, which was significantly different (p < .001) than that of BCCs. CONCLUSIONS: Our study shows that TRPS1 may be an effective discriminatory marker for BCCs and SCCs. It also has a role in distinguishing BCCs from EMPSGCs.

Poroid Hidradenoma: Case Report and Comprehensive Review of the Literature.

Poroid hidradenoma (PH) is a rare benign adnexal tumor of eccrine differentiation. It is the rarest of the four described variants of poroid neoplasms. PHs characteristically share a hybrid of the architectural features of the hidradenoma, namely, tumor cells are entirely intradermal with both solid and cystic components, and the cytologic characteristics of the poroid neoplasms, containing predominantly poroid and cuticular cells. Many published reports of PH since its original discovery in 1990 state that "very few" cases of PH can be found in the literature. Here, we have identified a total of 75 published accounts of PH, including the case presented here, as well as the associated patient demographics, lesion characteristics, treatment, and outcomes. We suggest that while uncommon, PH is likely not exceptionally rare and could be an underreported diagnosis.

Bleomycin Electrochemotherapy of Dermal Cylindroma as an Alternative Treatment in a Rare Adnexal Neoplasm: A Case Report and Literature Review.

BACKGROUND: Brooke-Spiegler syndrome is a rare autosomal dominant disorder characterized by the continuous development of multiple benign skin appendage tumors. It is treated usually by repeated standard surgery. Here, we present a case study where electrochemotherapy (ECT) with bleomycin was used as an effective alternative approach in treating advanced dermal cylindromatosis of the head and neck in a patient with Brooke-Spiegler syndrome. PATIENTS AND METHODS: A 45-year-old woman presented with multiple recurrent dermal cylindroma lesions on her scalp. Previous treatment consisted of several surgical excisions that resulted in psychological deterioration due to the formation of numerous scars and extensive alopecic areas. ECT was offered to provide tumor removal and disease control and to improve the patient's quality of life. RESULTS: The treatment was well tolerated, and a significant reduction in neoplastic tissue was achieved. Importantly, scalp skin condition significantly improved, regaining a fair follicular density on the margins. CONCLUSION: This report suggests the feasibility of bleomycin ECT as a less invasive alternative option for controlling multiple scalp cylindroma lesions with cosmetically acceptable results, and improving quality of life.

Genetic and Immunohistochemical Profiling of Mammary Hidradenoma and Comparison to Mucoepidermoid Carcinoma.

Mucoepidermoid carcinoma (MEC) is exceedingly rare in the breast, with <45 cases reported in the literature. Although estrogen receptor/progesterone receptor/human epidermal growth factor 2 triple-negative, MEC is characterized as a special subtype of breast carcinoma with significantly better prognosis than conventional basal-type tumors. Cutaneous hidradenoma (HA) is considered a benign adnexal neoplasm showing histomorphologic overlap with MEC. Rare cases of HA have also been reported in the breast, but these are relatively uncharacterized. In this study, we examined the clinicopathologic, immunohistochemical (IHC), and genetic features of 8 breast HAs, in comparison to 3 mammary MECs. All cases were positive for MAML2 break-apart fluorescence in situ hybridization. Eight cases demonstrated a CRTC1::MAML2 fusion, and one MEC harbored a CRTC3::MAML2 fusion; the latter is a novel finding in the breast. Mutational burden was very low, with only one HA exhibiting a MAP3K1 pathogenic alteration. By IHC, both MEC and HA demonstrated cell type-dependent expression of high- and low-molecular-weight keratins and p63, as well as negative to low-positive estrogen receptor and androgen receptor. Smooth muscle myosin and calponin highlighted an in situ component in the 3 cases of MEC; expression of these myoepithelial markers was negative in HAs. Additional distinguishing characteristics included the growth pattern and tumor architecture, the presence of glandular/luminal cells in HA, and overall higher IHC expression of SOX10, S100 protein, MUC4, and mammaglobin in MEC. Morphologic findings were also compared to a series of 27 cutaneous nonmammary HAs. Mucinous and glandular/luminal cells were identified in significantly more mammary HAs than nonmammary lesions. The findings provide insight into the pathogenesis of MAML2-rearranged neoplasms of the breast, underscore the overlapping genetic features of MEC and HA, and highlight similarities to their extramammary counterparts.

A rare case of cutaneous myxoma with trichofolliculoma-like features.

Carney complex is a rare genetic disorder associated with a number of cutaneous lesions, especially cutaneous myxomas. We present a rare case of cutaneous myxoma (superficial angiomyxoma) with trichofolliculoma-like features in a patient with Carney complex, and explore how the associated histopathology provides critical context for elucidating the etiology of this benign neoplasm.

Childhood pilomatrixoma mimicking malignant small round blue cell tumor with positivity for CD99: Potential pitfall in cytology.

Pilomatrixoma is a relatively rare benign skin appendageal tumor, often presenting in the pediatric age group as a nodular lesion and most commonly involving the head and neck, making it amenable to primary fine needle aspiration (FNA) diagnosis. We report the clinical and histopathological findings of two cases of pilomatrixoma in children, both of which were initially misdiagnosed as small round blue cell tumors due to high cellularity and misinterpretation of the proliferating basaloid cells. Histopathology revealed basal cell proliferation and mitoses indicating that they were progressive, early lesions. The first case showed membranous positivity for CD99 which prompted a diagnosis of Ewing sarcoma. Awareness of the morphological spectrum including positivity for CD99 and careful evaluation of cell block histology could have averted the misdiagnosis. Pilomatrixoma should be included as an important differential diagnosis when faced with primitive-appearing cells on FNA, especially in children with mass lesions in the head and neck region.

Poroid Hidradenoma: Dermoscopic and In Vivo Reflectance Confocal Microscopic Description.

Poroid hidradenoma (PH) is a rare, benign adnexal neoplasm usually presenting as a solitary, well circumscribed, asymptomatic papule or nodule that appears reddish and is occasionally tender. Since 1990, only a few cases of PH have been reported. We present a case of PH on the medial surface of the thigh and describe, for the first time, the dermoscopic and reflectance confocal microscopic (RCM) features in correlation with histology. A 67-year-old woman with unremarkable family or past medical history presented with a nodular lesion on the medial surface of the right thigh. The lesion had appeared 4 months earlier and rapidly enlarged. Physical examination revealed a 7 × 5 mm, non-tender, reddish nodule with clinically distinct margins. Dermoscopy showed central blue-grey pigmented areas, a polymorphous vascular pattern with arborizing, glomerular and hairpin vessels surrounded by white halos. RCM revealed an ovoid, well-outlined tumor, with a central area containing cells with distinctive morphologies, two types of tumor cells, tubular hypo-reflective structures, and rectilinear vessels in the stroma. These findings correlated with histological features, which established the diagnosis of PH. Even though the diagnosis of PH remains histopathological, non-invasive tools, such as RCM, can help rule out several malignancies, therefore reducing surgical-associated comorbidity.

Genital syringocystadenocarcinoma papilliferum: An unusual location and review of the literature.

Syringocystadenocarcinoma papilliferum (SCACP) is an extremely rare adnexal neoplasm of the sweat glands. It is believed to arise from the malignant transformation of syringocystadenoma papilliferum (SCAP). The majority of cases present on the head and neck and up to 17% of cases show metastatic progression. These tumors seldom occur in the anogenital area and, to date, only one case has been reported on the penis. Here, we report a rare case of SCACP in a 65-year-old man who presented with an erythematous, non-healing, ulcerated lesion on the penis.

Surgical management and lymph-node biopsy of rare malignant cutaneous adnexal carcinomas: a population-based analysis of 7591 patients.

OBJECTIVE: To analyze the prognosis of cutaneous adnexal malignancies, survival relative to surgical management, and utility of lymph-node biopsy. DESIGN: Population-based study of the SEER-18 database from 1975 to 2016. PARTICIPANTS: 7591 patients with sweat gland carcinoma, hidradenocarcinoma, spiradenocarcinoma, sclerosing sweat duct tumor/microcystic adnexal tumor (SSDT/MAC), porocarcinoma, eccrine adenocarcinoma, and sebaceous carcinoma RESULTS: Five-year OS ranged from 68.0 to 82.6%, while 5-year DSS ranged from 94.6 to 99.0%. The majority of patients were treated with narrow (42.4%) or wide local excision (16.9%). DSS at 5 years showed that patients with stage IV had significantly poorer survival (50.3%) than I, II, or III (99.3%, 97.8%, and 89.0% respectively). 5-year OS was significantly higher for narrow excision (excision with < 1 cm margin, 78.5%) than observation (65.0%), excisional biopsy (66.8%), or wide local excision (WLE, 73.2%). Lymph-node biopsy was performed in a minority of cases (8.1%) and patients showed no significant difference in survival based on nodal status. The sensitivity and specificity of lymph-node biopsy for all malignancies were 46% and 80%, respectively. The PPV and NPV for that group were 0.46 and 0.80, respectively. Invasion of deep extradermal structures was a poor predictor of nodal positivity. CONCLUSIONS: These malignancies have excellent DSS. Narrow excisions demonstrate better 5-year DSS and OS compared with WLE. Lymph-node biopsy is a poor predictor of survival in advanced stage disease and utility is limited.