Patients with a new-onset cutaneous sebaceous neoplasm following immunosuppression should be evaluated for Muir-Torre syndrome with germline mismatch repair gene mutation analysis: case reports.

Patients with Muir-Torre syndrome may have a systemic malignancy and a sebaceous neoplasm such as an adenoma, epithelioma, and/or carcinoma. The syndrome usually results from a germline mutation in one or more mismatch repair genes. Iatrogenic or acquired immunosuppression can promote the appearance of sebaceous tumors, either as an isolated event or as a feature of Muir-Torre syndrome and may unmask individuals genetically predisposed to the syndrome. Two iatrogenically immunosuppressed men with Muir-Torre syndrome features are described. Similar to these immunocompromised men, Muir-Torre syndrome-associated sebaceous neoplasms have occurred in solid organ transplant recipients, human immunodeficiency virus-infected individuals, and patients with chronic diseases who are treated with immunosuppressive agents. Muir-Torre syndrome-associated sebaceous neoplasms occur more frequently and earlier in kidney recipients, who are receiving more post-transplant immunosuppressive agents, than in liver recipients. The development of sebaceous neoplasms is decreased by replacing cyclosporine or tacrolimus with sirolimus or everolimus. Specific anti-cancer vaccines or checkpoint blockade immunotherapy may merit exploration for immune-interception of Muir-Torre syndrome-associated sebaceous neoplasms and syndrome-related visceral cancers. We suggest germline testing for genomic aberrations of mismatch repair genes should routinely be performed in all patients-both immunocompetent and immunosuppressed-who develop a Muir-Torre syndrome-associated sebaceous neoplasm.

S1-Guideline Sebaceous Carcinoma.

Sebaceous gland carcinomas are rare malignant cutaneous adnexal tumors with sebocytic differentiation. The typical predilection area is the head and neck region, where sebaceous gland carcinomas are the most common malignant adnexal tumors of the skin. According to their localization a distinction is made between periocular and extraocular sebaceous gland carcinomas. Muir-Torre syndrome (MTS) should always be ruled out if it is suspected. In terms of prognosis, sebaceous gland carcinomas are potentially aggressive tumors with a clear tendency to recur and metastasize. Only small extraocular sebaceous gland carcinomas that have been completely resected have a very good prognosis. Sebaceous gland carcinomas most frequently metastasize lymphogenously to regional or distant lymph nodes; organ metastasis occurs less frequently. Periocular sebaceous gland carcinomas have a higher metastasis rate (up to 15%) than extraocular sebaceous gland carcinomas (up to 2%). Complete micrographically controlled surgery (MCS) of the primary tumor is the therapy of first choice, regardless of periocular or extraocular localization. Adjuvant or therapeutic radiotherapy may be considered. There is currently no established standard therapy for advanced, inoperable, or metastatic sebaceous gland carcinomas. Local procedures and systemic therapies such as chemotherapy or immunotherapy can be considered. The procedure should be determined individually by an interdisciplinary tumor board. Close follow-up care is recommended for these potentially aggressive carcinomas.

Sebaceous carcinoma in a 54-year-old Black African man after cancer chemotherapy: a case report.

BACKGROUND: Sebaceous carcinoma is a very rare malignant skin adnexal tumor that is occasionally aggressive. We have not seen a case of sebaceous carcinoma in our center in the last 10 years. It is extremely rare in Black Africans. CASE PRESENTATION: We described the case of a 55-year-old man African man who presented to our ophthalmologist with complaints of growth on the right upper eyelid for 8 months. He had surgery and chemotherapy for rectal carcinoma 6 years prior to presentation and received his last dose of chemotherapy 5 years before seeing our ophthalmologist. There was a history of spontaneous unprovoked bleeding from the lesion. He subsequently underwent surgical excision under general anesthesia. Histology of the mass showed an effaced architecture due to proliferating malignant epithelial cells disposed as trabecules, solid nests, and tongues. The microscopic features of widespread multivacuolated cytoplasm of the neoplastic cells led us to conclude that the tumor was a sebaceous carcinoma. The patient is alive and well. CONCLUSION: Sebaceous carcinoma is a rare malignant skin adnexal tumor in Black Africans. It can present as an eyelid mass with spontaneous bleeding. It can follow cancer chemotherapy either because of its association with other tumors in Muir-Torre syndrome or because of mutagenic effects of chemotherapeutic agents.

Androgen Receptor Immunohistochemistry is Superior to PRAME for the Differentiation of Sebaceous Carcinoma From Primary Cutaneous Basaloid Mimics.

ABSTRACT: Cutaneous sebaceous neoplasia comprises a spectrum of disease ranging from benign adenomas to malignant carcinomas. The hallmark of these lesions is sebaceous differentiation. However, poorly-differentiated sebaceous carcinoma (SC), which lacks significant overt sebaceous differentiation, can show morphologic overlap with a variety of other basaloid cutaneous neoplasms. The accurate classification of SC is essential not only for diagnosis, but also because of the potential association with Muir-Torre syndrome. Androgen receptor (AR) is a sensitive, but not entirely specific immunohistochemical marker that has been used for the diagnosis of SC. PReferentially expressed Antigen in MElanoma (PRAME) demonstrates strong cytoplasmic labeling of mature sebocytes and has been reported to be expressed in a variety of sebaceous neoplasms, including in the basaloid cell component. Therefore, we sought to compare the diagnostic use of cytoplasmic PRAME expression with that of AR for the distinction of SC from a cohort of basaloid cutaneous mimics; namely basal cell carcinoma, basaloid squamous cell carcinoma, pilomatricoma, cutaneous lymphadenoma, and extra-mammary Paget disease. We report that cytoplasmic PRAME expression is uncommon in poorly differentiated SC, and although specific, it shows very low sensitivity (22%). In contrast, AR was moderately sensitive (66%) and highly specific (92%) for the distinction of SC from basaloid mimics. These attributes, in addition to the nuclear expression of AR in the sebocytic and basaloid components of SC, suggest that AR is superior to PRAME for the diagnosis of SC.

Cytomorphological features of sebaceous carcinoma of the breast.

Sebaceous carcinoma of the breast is an extremely rare histological subtype of breast cancer, with fewer than 30 cases reported to date. Because of its extremely rare histological presentation, there are few case reports that highlight its cytological findings. In this case report, the cytomorphological features of a sebaceous carcinoma of the breast are described in detail. Cytomorphological analysis revealed atypical cells presenting predominantly as loose clusters. No tubular or papillary structures were evident in the clusters and no mucin production was observed. The diagnosis of sebaceous carcinoma of the breast requires prominent sebaceous differentiation of cells. In Papanicolaou-stained smears, the differentiated tumor cells were found within the yellowish clusters. When these yellowish clusters were observed at high magnification and shifted out of focus, the sebaceous differentiation of tumor cells could be recognized. This finding is an advantage of observing Papanicolaou-stained specimens. Like previous reports, some individual cells showing sebaceous differentiation were also observed. In cases where many yellowish clusters appear, close observation of the interior of the clusters can confirm the presence of sebaceous differentiation of tumor cells and serve as a diagnostic clue for the cytological diagnosis of sebaceous carcinoma of the breast.

Periocular sebaceous carcinoma: updates in the diagnosis, treatment, staging, and management.

Periocular sebaceous carcinoma (PSC) is a rare, aggressive, and potentially metastatic adnexal malignancy. Due to the ability of PSC to resemble several benign and malignant conditions, diagnosis is often delayed or mistaken. In addition, even with a known diagnosis, choosing the right treatment is still an open debate. For this reason, we decided to review the most up-to-date literature on PSC and propose a dedicated procedural protocol to help clinicians when dealing with PSC. A PubMed search was carried out using the terms "Sebaceous Carcinoma", "Adnexal Periocular Cancer", "Sebaceous Carcinoma AND eyelid", "Periocular Sebaceous Carcinoma", and "Ocular Adnexa". Pertinent studies published in English from 1997 up to December 2022 were compared to the selection criteria and if suitable, included in this review. Through the initial search, 84 articles were selected. Of these, 36 were included in the final study. Several papers explored different diagnostic and therapeutic strategies regarding PSC diagnosis and management. In light of the current literature review and the multidisciplinary experience of three clinical centers, a dedicated procedural protocol is proposed. PSC diagnosis may be achieved through accurate clinical evaluation, but it requires histopathologic confirmation, which can be challenging. Dermoscopy, in vivo reflectance confocal microscopy, and optical coherence tomography may facilitate PSC clinical examination, while immunohistochemistry stains may support histological diagnosis. Appropriate disease staging is necessary before choosing the treatment, as local disease requires radically different treatment compared to advanced disease. In addition, recent innovations in nonsurgical treatments, including radio-chemotherapy, immunotherapy, and targeted therapy, may be a viable option in the most challenging cases.

Extra-ocular sebaceous carcinoma - A rare case report.

Sebaceous gland carcinoma is a rare and aggressive skin cancer derived from the sebaceous glands. Sebaceous carcinomas are divided into those occurring in ocular (75%) and extra-ocular locations. A 45-year-old female patient presented with rapidly growing swelling over the upper back region. It was provisionally diagnosed as an infected sebaceous cyst, and an excision biopsy was received in the pathology department. Histopathology was reported as sebaceous carcinoma, Grade II, Stage P T3 Nx. Immunohistochemistry was positive for epithelial membrane antigen. Sebaceous carcinoma accounts for 0.2-4.6% of all malignant cutaneous neoplasms, and the estimated rate of occurrence is only 1-2 per 1 million individuals per year. These tumors frequently present with a painless sub-cutaneous nodule, but they can also present as pedunculated lesions, irregular mass, or diffuse thickening of the skin. Hence, they are misinterpreted as other benign tumors or inflammatory conditions, thereby leading to delay in diagnosis, inappropriate treatment, increased morbidity, and mortality.

Prognostic Significance of Tumor-Infiltrating Lymphocytes and High-Risk Human Papillomavirus in Ocular Sebaceous Carcinoma: A Comprehensive Analysis.

High-risk human papillomavirus (hrHPV) and tumor-infiltrating lymphocytes (TILs) are known to have prognostic significance in oropharyngeal squamous cell carcinoma. However, their significance in ocular sebaceous carcinoma (OSC) remains unverified because of the rarity of the condition. This study aimed to investigate the association between clinicopathologic features, biomarkers, and hrHPV infection and their potential to predict prognosis in OSC patients. We analyzed the clinicopathologic features of 81 OSC patients from Asan Medical Center between 2000 and 2022. Seventeen biomarkers and hrHPV were examined using immunohistochemistry and DNA in situ hybridization on tissue microarray cores. hrHPV was identified in 31 cases (38.3%). Univariate analysis revealed that hrHPV infection was associated with comedonecrosis (P = .032), high Ki-67 labeling index (≥30%, P = .042), lower expression of E-cadherin (P = .033), and loss of expression of zinc finger protein 750 (P = .023). Multivariate analysis revealed that loss of expression of zinc finger protein 750 (P = .026) remained an independently associated factor for hrHPV. Progression-free survival analysis was performed on 28 patients who were continuously observed for more than 5 years. During a median follow-up duration of 86 months, recurrence or metastasis developed in 14 patients (50%) within the survival cohort, occurring at a median time of 48 months after excision. Univariate analysis indicated that recurrence or metastasis was associated with tumor size (P = .010), high TILs (≥10%; P = .025), lymphovascular invasion (P = 0.043), site of origin (P = .025), and high expression of bcl-2-associated athanogene 3 (P = .039). Multivariate analysis demonstrated that high TILs (P = .017) and site of origin (P = .025) were independent prognostic factors. The prognosis of OSC was hrHPV-independent, and a better prognosis was associated with the site of origin in the order of the gland of Zeis, meibomian gland, and multicentric site, as well as with high TILs.

Nectin-4 expression in a subset of cutaneous adnexal carcinomas: A potential target for therapy with enfortumab vedotin.

BACKGROUND: Enfortumab vedotin (EV) is an antibody-drug conjugate directed against Nectin-4 that is used to treat urothelial carcinoma. Nectin-4 is inherently expressed in the skin and adnexal structures. Since therapeutic options for cutaneous adnexal carcinomas are limited, we sought to evaluate Nectin-4 expression in adnexal carcinomas and benign adnexal neoplasms to identify tumors that are potentially targetable with EV. METHODS: Eight sebaceous carcinomas (seven periocular and one lymph node metastasis), eight digital papillary adenocarcinomas, seven squamoid eccrine ductal carcinomas, eight poromas, eight trichilemmomas, and seven sebaceous adenomas were subjected to immunohistochemical staining for anti-Nectin-4 antibody. H-scores for Nectin-4 expression were calculated. RESULTS: Benign adnexal neoplasms had a significantly lower mean (±SD) Nectin-4 H-score (142.6 ± 39.1) than did the adnexal carcinomas (198 ± 90.8; p = 0.006). Nectin-4 was expressed in 91% (21/23) of adnexal carcinomas. Sebaceous carcinomas frequently exhibited high expression of Nectin-4 (88% [7/8]), with a mean (±SD) H-score (258.1 ± 58.4) significantly higher than those for digital papillary adenocarcinomas (197.5 ± 52.5; p = 0.035) and squamoid eccrine ductal carcinomas (131.4 ± 114.1; p = 0.031). Sebaceous carcinomas also had significantly higher H-scores than did sebaceous adenomas (186.4 ± 25.0; p = 0.013). CONCLUSIONS: Increased Nectin-4 expression in a subset of cutaneous adnexal carcinomas, particularly sebaceous carcinomas, reveals that EV is a potential therapeutic option for these tumors.

Mosaic Muir Torre Syndrome: Keratoacanthoma as a Piece of the Puzzle.

ABSTRACT: Lynch syndrome is an inherited condition, which increases the risk of numerous visceral malignancies and cutaneous tumors such as keratoacanthomas and sebaceous tumors. It is typically identified by immunohistochemistry of tissue taken from tumors or through genetic testing with next-generation sequencing. Diagnosing Lynch syndrome becomes more complex when the individual is mosaic for the relevant pathogenic variant. There are very few cases of this reported in the medical literature. It is even more unusual for the diagnosis to be made based on testing of a keratoacanthoma lesion. We report a case where immunohistochemistry of a keratoacanthoma helped make a diagnosis of mosaic Lynch syndrome. We will explore how mosaicism should be considered when a phenotype is strong, even if next-generation sequencing reports no pathogenic or likely pathogenic variant and how lesions such as keratoacanthomas can have a role in the early detection and treatment of future malignancies.

Diagnosis and treatment of malignant eyelid tumors.

BACKGROUND: Malignant tumors of the eyelid are much less frequent than benign eyelid alterations. These are frequently incidental findings without symptoms which are often overlooked or misinterpreted by patients. OBJECTIVE: This article gives an overview of clinical aspects, diagnostics and treatment of the five most common malignant eyelid tumors and exemplarily explains the essential principles of evidence-based treatment of malignant eyelid tumors. METHODS: This narrative review was prepared based on a selective literature search. The depiction of the treatment of eyelid tumors is supported by illustrations of clinical cases. RESULTS: The medical history and inspection provide initial indications of malignancy. Every eyelid change suspected of being malignant should be examined histologically to confirm a diagnosis. By far the most common malignant eyelid tumor in Europe is basal cell carcinoma, which metastasizes only in exceptional cases. Squamous cell carcinomas, sebaceous adenocarcinomas, melanomas and Merkel cell carcinomas occur much less frequently. In these cases, potential metastasis in particular must be considered when making the diagnosis and staging has to be initiated. Surgical excision into healthy tissue with tumor-free margins is the gold standard for malignant eyelid tumors. Non-surgical adjuvant or neoadjuvant forms of evidence-based treatment can be initiated based on the individual case to minimize the risk of recurrence and metastasis. CONCLUSION: It is essential to recognize eyelid changes at an early stage, to classify them correctly and to initiate the appropriate treatment. The interaction between the general condition and the personal needs of a patient as well as state of the art medicine are the keys to a good personalized treatment.

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.

Survival outcomes of rare cutaneous malignancies within an insured cohort of patients, 1988-2018.

BACKGROUND: There are limited survival data on cutaneous angiosarcoma (CAS), dermatofibrosarcoma protuberans (DFSP), Merkel cell carcinoma (MCC), and sebaceous carcinoma (SC). OBJECTIVE: To analyze survival trends in CAS, DFSP, MCC, and SC among a racially diverse, insured cohort of patients. METHODS: Using data from the Kaiser Permanente Southern California Cancer Registry, we identified adults diagnosed with CAS, DFSP, MCC, or SC between January 1, 1988 and December 31 2018, followed through December 31, 2021. RESULTS: Our cohort consisted of 83 diagnoses of CAS, 490 diagnoses of DFSP, 411 diagnoses of MCC, and 249 diagnoses of SC. Our analysis revealed no significant differences in overall or disease-specific 1000 person-years mortality rates among our populations of non-Hispanic Whites, Hispanics, African American/Blacks, and Asian American/Pacific Islanders diagnosed with CAS, DFSP, MCC, or SC. On multivariate analysis, controlling for patient and tumor characteristics, there was similarly no increased risk of overall mortality for minorities diagnosed with CAS, DFSP, MCC, or SC. LIMITATIONS: Retrospective nature of the analysis and small sample size. CONCLUSION: Contrary to existing literature, our results show a notable lack of racially driven survival disparities among insured individuals with CAS, DFSP, MCC, and SC, emphasizing the importance of health care coverage.