Based on Immune Microenvironment and Genomic Status, Exploring Immunotherapy in Advanced Hidradenocarcinoma: A Retrospective Analysis.

There are no standard treatment guidelines for hidradenocarcinoma, and the immune microenvironment and genomic data are very limited. Thus, in this study the immune microenvironment and genomic indicators in hidradenocarcinoma was investigated, and immunotherapy for hidradenocarcinoma was initially explored. Forty-seven hidradenocarcinoma patients were retrospectively collected. Immunohistochemical staining was performed to identify CD3/CD8+ T cells and programmed death ligand-1 expression. In total, 89.4% and 10.6% of samples had Immunoscores of 0-25% and 25-70%. Tumour proportion score distribution was as follows: tumour proportion score < 1% in 72.4%, 1-5% in 17.0%, and > 5% in 10.6%. Combined positive score distribution was as follows: combined positive score < 1 in 63.8%, 1-5 in 14.9%, and > 5 in 21.3%. Next-generation sequencing revealed that TP53 (33%), PI3KCA (22%), and ERBB3 (22%) were the most frequently mutated genes. The PI3K-Akt signalling pathway, growth, and MAPK signalling pathways were significantly enriched. Five patients had a low TMB (< 10 muts/Mb), and 9 patients had MSS. Three patients treated with immune combined with chemotherapy achieved significant tumour regression, and the progression-free survival was 28.8 months. In conclusion, the hidradenocarcinoma immune microenvironment tends to be noninflammatory. Evidence-based targets for targeted therapy are lacking. Immunotherapy combined with chemotherapy may be better for most advanced hidradenocarcinoma patients with a noninflammatory microenvironment.

Case of eccrine chondroid syringoma of the upper lip.

Chondroid syringoma (CS) is a benign, slow-growing mixed tumour that arises from the sweat glands and usually presents in the head and neck area. Histopathological examination is important for proper diagnosis, as CS is often confused with epidermal cysts due to its rare presentation. This article presents a man in his 40s with a right upper lip mass that emerged 6 months prior to presentation. An intraoral surgical excision was performed and the histopathological analysis revealed solid epithelial cells that formed multiple, non-branching ducts lined by cuboidal epithelium. Cystic spaces were filled by heterogeneous eosinophilic material embedded in chondromyxoid stroma. Histopathology identified the lesion as an eccrine-variant CS. The patient recovered well.

Challenging diagnosis of male intraductal papilloma masquerading as eccrine hidradenoma in the breast: Case report.

RATIONALE: This article presents a challenging case involving an elderly male patient with a misdiagnosed intraductal mammary papilloma initially identified as a sweat adenoma through ultrasound imaging. The study aims to explore the histopathology, clinical presentations, and sonographic features of both conditions, emphasizing the contributing factors to the diagnostic misstep. PATIENT CONCERNS: A 61-year-old male reported a persistent left breast mass, along with pain and swelling, spanning a 6-month duration. DIAGNOSES: Ultrasound examination indicated a deep, square, mixed-echo mass in the left nipple, initially suggestive of a sweat adenoma. However, subsequent pathological analysis following resection under general anesthesia confirmed an intraductal papilloma. INTERVENTION: The patient underwent surgical resection of the left breast mass under general anesthesia. OUTCOME: Post-surgery, the patient exhibited satisfactory recovery; however, regrettably, he was lost to follow-up. LESSONS: This study underscores the challenge in differentiating between clear cell sweat adenoma and male intraductal mammary papilloma solely based on ultrasonic characteristics. It emphasizes the susceptibility of ultrasound-based diagnoses to misinterpretation, highlighting the critical need for a comprehensive pathological examination to establish a definitive diagnosis.

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.

Recurrent GATA3 P409Afs*99 Frameshift Extension Mutations in Sweat-gland Carcinoma With Neuroendocrine Differentiation.

Sweat-gland carcinoma with neuroendocrine differentiation (SCAND) was recently proposed as a new cutaneous adnexal neoplasm with neuroendocrine differentiation; however, its genetics are not well known. Herein, we performed clinicopathologic and genetic analyses of 13 SCAND cases and 5 control cases of endocrine mucin-producing sweat gland carcinoma (EMPSGC). The SCAND group included 11 males and 2 females with a median age of 68 years (range, 50 to 80 y). All SCAND lesions occurred in the ventral trunk or genital area. Of the 13 SCAND cases, 9 and 5 exhibited lymph node and distant metastases, respectively. Three (23.1%) patients with SCAND died of the disease. In contrast, neither metastasis nor mortality was confirmed in the EMPSGC cases. Immunoexpression of the androgen receptor, c-Myb, and MUC2 was limited in SCAND, whereas EMPSGC frequently expressed these immunomarkers. GATA3 P409Afs*99 extension mutations were detected in 7 (53.8%) of the 13 SCAND cases, using Sanger or panel sequencing. All 7 SCAND cases with GATA3 mutations were located in the genital, inguinal, or lower abdominal regions, whereas 5 of the other 6 SCAND cases were located in the anterior upper to mid-trunk. No GATA3 mutations were detected in the EMPSGC cases (0/5, 0%). These clinicopathologic and genetic findings support SCAND as a tumor entity distinguishable from EMPSGC. In addition, the characteristic frameshift extension mutations in GATA3 contribute to the establishment of the tumor-type concept of SCAND.

Cutaneous Malignant Mixed Tumor With Pulmonary Metastasis: A Case Report and Literature Review.

BACKGROUND: Cutaneous malignant mixed tumor (MMT) is a rare sweat gland-derived tumor characterized by admixed malignant epithelial cells and chondromyxoid stroma. Approximately 50 cases have been described in the literature. Metastasis, which may occur in more than one-third of cases, is most common in the lung. METHODS: We summarized the clinicopathologic features of a patient with cutaneous MMT metastatic to the lungs. A literature review of similar cases was completed using Web of Science, Scopus, and PubMed databases. RESULTS: A woman in her 70s presented with an enlarging mass on her left eyebrow; histopathologic examination showed large islands of atypical cells with increased mitotic activity, admixed with necrosis on a background of fibrotic and chondromyxoid stroma. Multiple lung nodules were identified during follow-up. Examination of a pulmonary core needle biopsy specimen was consistent with metastatic cutaneous MMT. Literature review identified 10 cases published between 1980 and 2017. Most primary tumors were large (≥4 cm). Local recurrence was uncommon, and the lung was the only metastatic site in 5 cases. Histopathologically, metastatic tumors were described as more cellular, with diminished stromal tissue compared with the primary lesion. CONCLUSION: This is 1 of the 11 reports of cutaneous MMT with metastasis to the lungs found in the English-language literature published after 1980. Of note, most reports were published before 1990, making this case study one of the few contemporary descriptions of cutaneous MMT with pulmonary metastases. We think that the present case report will increase the awareness of this rare tumor.

Five-year pattern of adnexal tumors of the skin in Ethiopia.

BACKGROUND: Adnexal tumors of the skin are rare neoplasms that encompass a wide range of dermatologic entities. Here, we investigated the pattern of adnexal tumors of the skin in the All African Leprosy and Tuberculosis Rehabilitation and Training Center (ALERT) hospital retrospectively. METHODS: A hospital-based retrospective study was conducted at ALERT from histopathology records in the Armauer Hansen Research Institute (AHRI) pathology laboratory of patients diagnosed with any of the skin adnexal tumors during the time period January 2017 to December 2021. A structured data extraction sheet was used. Data entry was done using EpiData 4.6.0.6. Data were analyzed using SPSS version 25. RESULT: A total of 146 skin adnexal tumors were identified making the magnitude 2.8% of total biopsies. The 3rd decade of life was found to be the most common age group. Male-to-female ratio was 1 : 1.05. Majority of the tumors were benign (82.2%) and had sweat gland differentiation at 48.6%. Poroma (10.9%) was the most frequent tumor, whereas porocarcinoma (6.8%) made up the most frequent malignant tumor. The most common site was the head and neck region (48.6%). Only 21.2% of the tumors were correctly identified clinically. CONCLUSION: The magnitude of skin adnexal tumors is found to be slightly higher than other similar studies which could be because it was carried out in the largest dermatologic center in the country. The most common skin adnexal tumors identified, their localizations, and lines of differentiation are all in line with other studies. Histopathologic examination is mandatory for the accurate diagnosis of these tumors.

Molecular Profiling of Syringocystadenocarcinoma Papilliferum Reveals RAS-Activating Mutations.

CONTEXT.­: Syringocystadenocarcinoma papilliferum (SCACP) is a rare adnexal carcinoma and the malignant counterpart of syringocystadenoma papilliferum (SCAP), which is commonly located on the head and neck and may arise in association with a nevus sebaceus. RAS mutations have been identified in both SCAP and nevus sebaceus. OBJECTIVE.­: To evaluate the clinicopathologic and molecular features of SCACPs, which have not been previously explored. DESIGN.­: We obtained 11 SCACPs from 6 institutions and reviewed the clinicopathologic features. We also performed molecular profiling using next-generation sequencing. RESULTS.­: The cohort comprised 6 women and 5 men with ages ranging from 29 to 96 years (mean, 73.6 years). The neoplasms occurred on the head and neck (n = 8; 73%) and extremities (n = 3; 27%). Three tumors possibly arose in a nevus sebaceus. A total of 4 cases showed at least carcinoma in situ (adenocarcinoma, n = 3; squamous cell carcinoma [SCC], n = 1), and 7 cases were invasive (SCC, n = 5; mixed adenocarcinoma + SCC, n = 2). A total of 8 of 11 cases (73%) had hot spot mutations consisting of HRAS (n = 4), KRAS (n = 1), BRAF (n = 1), TP53 (n = 4), ATM (n = 2), FLT3 (n = 1), CDKN2A (n = 1), and PTEN (n = 1). All 4 cases with HRAS mutations occurred on the head and neck, whereas the KRAS mutation occurred on the extremity. CONCLUSIONS.­: RAS-activating mutations were detected in 50% of the cases, of which most (80%) involved HRAS and occurred on the head and neck, which shows overlapping features with SCAP, supporting that a subset may arise as a result of malignant transformation and likely an early oncogenic event.

Spindle cell porocarcinoma with a novel YAP1::MAML3 fusion.

Porocarcinomas are rare sweat gland cancers representing the malignant counterpart to benign poromas. Their diagnosis can be challenging, especially in the absence of an associated poroma or when the tumor is poorly differentiated. Since recurrent YAP1::MAML2 and YAP1::NUTM1 fusions have been identified in poroid tumors, molecular studies provide an opportunity to support the diagnosis in challenging cases. We describe a case of a female patient in her early 90s, with a polypoid mass of the hip. Histopathologically, there was a poorly differentiated malignant spindle cell tumor adjacent to a poroma. Because of the close association with a poroma and immunoreactivity for p40, a diagnosis of spindle cell porocarcinoma was rendered, which was further supported by YAP1 immunohistochemical studies. Antibodies targeting both the N-terminus and C-terminus confirmed YAP1 rearrangement in both the poroma and the spindle cell neoplasm. Subsequent targeted RNA sequencing revealed a YAP1::MAML3 gene fusion. MAML3 has previously not yet been reported as a YAP1 fusion partner in porocarcinoma. With the illustration of a rare spindle cell variant of porocarcinoma and the identification of a novel gene fusion, this case report expands the spectrum of morphologic and genomic aberrations associated with porocarcinoma.

Apocrine cystadenoma: A long-standing apocrine hidrocystoma with an adenomatous proliferation.

BACKGROUND: Apocrine cystadenoma is a rare, benign adenomatous cystic neoplasm, the pathogenesis of which is not fully understood. We sought to characterize the clinical, dermatoscopic, and histopathologic features of apocrine cystadenoma and its relationship to hidrocystoma. METHODS: We retrospectively analyzed cases of apocrine cystadenoma and hidrocystoma retrieved from the dermatopathology laboratory information system. RESULTS: Of the 350 cases apocrine cystic lesions, 13 cases of apocrine cystadenomas met the inclusion criteria. The age ranged from 20 to 84 years with an average of 64 years. They were long-standing (duration 3-15 years), slow-growing, large tumors usually found on the scalp. Dermatoscopy accentuated translucent light to dark blue color and prominent vessels that were present more at the periphery. All lesions were multilocular with columnar to cuboidal lining and decapitation secretion. A large portion of the lesion consisted of a simple nonproliferative epithelial lining, identical to that observed in apocrine hidrocystomas, while the proliferative adenomatous component made up a smaller portion with two patterns: (1) tubular proliferation, which either protruded into the cystic cavity or expanded outward peripherally, or (2) papillary projections, which were multiple layers thick with fibrovascular core, sometimes accompanied by tubular proliferation. Immunohistochemical stains showed strong staining for p40 and a sparse number of cells stained for Ki-67 and p53. CONCLUSIONS: The long duration of the lesion and the large areas of simple apocrine epithelial lining suggest that apocrine cystadenomas arise from long-standing apocrine hidrocystomas. However, the retrospective nature of the study from a single institution is a limitation.

Apocrine carcinoma with marked sebocyte-like cytological features: A report of two cases.

Apocrine carcinoma cases with sebaceous differentiation have not been reported and can be misdiagnosed as sebaceous carcinoma. We present two cases of apocrine carcinoma with marked sebocyte-like cytological features. Tumors were observed in the left axilla of a 68-year-old man (Case 1) and the right axilla of a 72-year-old man (Case 2). Both patients presented with multiple lymph node metastases. Histopathology revealed densely distributed solid nests of tumor cells containing foamy cytoplasm and enlarged round nuclei with prominent nucleoli. The tumor cells diffusely expressed adipophilin, PRAME (cytoplasmic pattern), androgen receptor, BerEP4, and GCDFP15 but did not express p63 in both cases. PIK3CA E726K and H1047R mutations were detected in Cases 1 and 2, respectively. Tumor location in the axilla, the presence of eosinophilic granular cytoplasm, prominent nucleoli, and PIK3CA mutations, immunoreactivity for BerEP4 and GCDFP15, and lack of p63 immunoexpression findings matched apocrine carcinoma characteristics, but not sebaceous carcinoma. Thus, apocrine carcinoma can demonstrate intracytoplasmic lipid accumulation and rarely exhibit sebocyte-like cytological features. Apocrine carcinoma should be distinguished from sebaceous carcinoma due to the former's higher metastatic potential and lack of association with Muir-Torre syndrome.

Clear-Cell Dermal Duct Tumor: Case Report and Literature Review.

ABSTRACT: Clear-cell dermal duct tumor is a benign adnexal neoplasm composed of dermal multiple solid islands of clear cells, displaying ductal differentiation. Histopathologically, lesions can be subdivided into 2 distinct subgroups: (1) "pure" clear-cell dermal duct tumors, entirely composed of clear cells, and (2) "mixed" clear-cell dermal duct tumors, showing an associated conventional poroid component. Such a subclassification may be significant for the differential diagnosis: the less frequent "mixed" variant may be more easily recognized because of the presence of poroid and cuticular cells and the more frequent "pure" variant is to be distinguished from many other benign and malignant dermal clear-cell epithelial tumors.

[Optical coherence tomography for the diagnosis and differentiation of cutaneous cysts: a case series]. / Diagnose und Differenzierung von kutanen Zysten mit optischer Kohärenztomographie: eine Fallserie.

Cutaneous cystic lesions (n = 35) were examined with optical coherence tomography. Cysts were visible as a hyporeflective roundish area with a clear margin; in some cases, the epidermis was thinned. Epidermal cysts, trichilemmal cysts, and hidrocystomas had a linear margin representing the epithelium of the cyst, whereas mucoid pseudocysts showed no linear margin. Trichilemmal and epidermal cysts presented with hyperreflective content that corresponds to keratin. By visualizing the margin and the content of the cyst, it was possible to differentiate between different types of cysts.