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Purpose: Intraepithelial sebaceous gland carcinoma is a rare form of sebaceous gland carcinoma, with 10 published case reports to date. The authors report the clinical, histological, and prognostic features of this rare carcinoma., Methods: This is a multicenter retrospective case series of patients from 3 Australian sites. Information collected included patient demographics, clinical risk factors, initial and subsequent presentations, histology results, management, and outcomes., Results: Twelve cases were identified. The average age of presentation was 72 years (range 52-92 years), with more females (n = 8) affected than males. The most common symptoms and signs were ocular irritation (n = 9) and eyelid mass (n = 8), with a predilection toward upper lid involvement. Five cases of sebaceous gland carcinoma were confirmed on initial histology. Initial management included wide local excision with margin control (n = 11), and primary topical mitomycin C (n = 1). Adjunctive conjunctival mapping biopsy was performed in 5 cases. Recurrence occurred in 7 cases, at an average of 31 months (range 7-83 months) after initial treatment. There were no cases of distant metastasis, however, 2 cases developed local invasion. Management of recurrences included exenteration (n = 2), further excisions alone (n = 3), and excision with adjuvant mitomycin C (n = 2)., Conclusions: Clinicians and pathologists should have a high index of suspicion for primary intraepithelial sebaceous gland carcinoma on the upper eyelid. Close follow-up is recommended, given the high risk of local recurrence., Competing Interests: The authors have no financial or conflicts of interest to disclose., (Copyright © 2024 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Purpose: Sebaceous carcinoma is the third most common nonkeratinocyte skin cancer in the United States with 1,000 cases per year. The clinicopathologic features of sebaceous carcinoma and benign sebaceous neoplasms (adenomas, sebaceomas) can overlap, highlighting the need for molecular biomarkers to improve classification. This study describes the genomic and transcriptomic landscape of sebaceous neoplasms in order to understand tumor etiology and biomarkers relevant for diagnosis and treatment., Experimental Design: We performed whole-genome sequencing (WGS) and whole-transcriptome sequencing (WTS) of sebaceous neoplasms from six academic and two federal healthcare facilities in the United States diagnosed between January 1, 1999, and December 31, 2021., Results: We evaluated 98 sebaceous neoplasms: 64 tumors (32 adenomas, 2 sebaceomas, 5 atypical sebaceous neoplasms, 25 carcinomas) had sufficient material for WGS, 96 tumors (42 adenomas, 11 sebaceomas, 8 atypical sebaceous neoplasms, 35 carcinomas) had sufficient material for WTS, and 62 tumors (31 adenomas, 2 sebaceomas, 5 atypical sebaceous neoplasms, 24 carcinomas) had sufficient material for combined WGS and WTS. Overall, we found decreased cholesterol biosynthesis and increased TP53 mutations, copy number gains (chromosome 6, 8q, and/or 18), and tumor mutation burden-high (>10 mutations/MB) in carcinomas compared to adenomas. Although diminished compared to adenomas, most carcinomas still had higher cholesterol biosynthesis than nonmalignant skin. Multiomics profiling also supported a precancerous model of tumor evolution with sebaceomas and atypical sebaceous neoplasms being likely intermediate lesions., Conclusions: The study findings highlight key diagnostic biomarkers for sebaceous carcinoma and suggest that immunotherapy and modulation of cholesterol biosynthesis could be effective treatment strategies., (©2024 American Association for Cancer Research.)

Eyelid sebaceous gland carcinoma (SGC) is an aggressive skin cancer characterized by a heightened risk of recurrence and metastasis. While surgical excision is the primary treatment, unraveling the molecular intricacies of SGC is imperative for advancing targeted therapeutic interventions and enhancing patient outcomes. This comprehensive review delves into the molecular landscape of eyelid SGC, emphasizing key genetic alterations, signaling pathways, epigenetic modifications, and potential therapeutic targets. Significant findings include aberrations in critical signaling pathways (β-catenin, lymphoid enhancer binding factor, hedgehog, epidermal growth factor receptor, P53, and P21WAF1) associated with SGC progression and poor prognosis. Notably, eyelid SGC manifests a distinctive mutational profile, lacking ultraviolet signature mutations in tumor protein 53 (TP53), indicating alternative mutagenic mechanisms. Next-generation sequencing identifies actionable mutations in genes such as phosphatase and tensin homolog (PTEN) and Erb-B2 receptor tyrosine kinase 2 (ERBB2), facilitating the emergence of personalized medicine approaches. Molecular chaperones, specifically X-linked inhibitor of apoptosis protein (XIAP) and BAG3, emerge as pivotal players in promoting tumor survival and proliferation. The review underscores the role of epithelial-mesenchymal transition, where regulators like E-cadherin, vimentin, and ZEB2 contribute to SGC aggressiveness. Epigenetic modifications, encompassing DNA methylation and microRNA dysregulation, further elucidate the molecular landscape. This review consolidates a comprehensive understanding of the molecular drivers of eyelid SGC, shedding light on potential therapeutic targets and providing a foundation for future investigations in diagnostic, prognostic, and personalized treatment strategies for this formidable malignancy., (Copyright © 2024 Copyright: © 2024 Indian Journal of Ophthalmology.)

Sebaceous carcinoma (SC) is a rare neoplasm affecting periocular and extraocular sites. If inadequately treated, it can recur and cause morbidity. Specific management guidelines have not been established. Wide local excision (WLE) has been traditionally used; however, Mohs micrographic surgery (MMS) can be advantageous because of complete margin assessment and tissue-sparing nature. This analysis aims to systematically review the surgical modalities used for the management of SC. Articles meeting eligibility criteria were identified using MEDLINE (via PubMed), Embase, Cochrane, and Scopus databases. All studies investigating surgical management of SC with WLE or MMS were considered. Seventy studies met inclusion criteria, including retrospective cohort studies, case series, and case reports. WLE was used in 32 studies, MMS in 29, and MMS and WLE in 9. Subgroup analysis showed that MMS has lower recurrence rates. For WLE, local, regional, and distant recurrence rates were 23.4%, 13.3%, and 11.0%, respectively, and for MMS, 6.8%, 4.3%, and 4.6%, respectively. Patients treated with WLE were more likely to have local recurrence than patients treated with MMS (P = 0.001). WLE cases were more likely to have a regional (P = 0.05) and distant recurrence (P = 0.001). Limitations of the study include heterogeneity of case reports, case series, and retrospective studies, variable follow-up times between the two groups, and large tumors included in the WLE category. In addition, disease-specific survival was not evaluated. MMS cases showed a superior outcome for local, regional, and distant recurrence, making it a good option for the management of SC., (© 2024 the International Society of Dermatology.)

Background. Sebaceous carcinoma in situ outside the ocular region is an exceedingly uncommon. It is an intraepidermal neoplasm originating from sebaceous glands limited to the epidermis with no invasion into the underlying dermis or beyond. Although sebaceous carcinoma in situ is predominantly observed in ocular regions, particularly the eyelids, instances of its occurrence in extraocular locations are infrequent, with only a limited number of examples reported in the literature. Case Presentation. A 63-year-old man presented with a left posterior arm lesion. Microscopic examination revealed a proliferation of poorly differentiated atypical neoplastic sebocytes confined to the epidermis with pleomorphic nuclei, prominent nucleoli, and clear cell changes. The neoplastic cells demonstrated positive staining for adipophilin, androgen receptor, epithelial membrane antigen, P63, BerEP4, and keratin 7. Microsatellite instability markers showed preserved nuclear staining for MLH1, PMS2, MSH2, and MSH6. A definitive diagnosis of sebaceous carcinoma in situ was rendered. Discussion. The distinctive histopathologic characteristics typically involve the presence of atypical sebaceous cells confined within the epidermis. Atypical cells often exhibit enlarged nuclei, increased mitotic activity, and prominent nucleoli. A panel of epithelial membrane antigen, adipophilin, and androgen receptors is essential for ensuring an accurate diagnosis. Conclusion. This report underscores the importance of considering sebaceous carcinoma in situ in diagnosis in atypical locations, emphasizing the need for a comprehensive histopathologic examination and immunohistochemical staining panel. This article aims to demonstrate the rarity of sebaceous carcinoma in situ in extraocular sites to broaden our understanding of its diverse clinical presentations., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Ocular adnexal sebaceous carcinoma (SebCA) represents one of the most clinically problematic periocular tumors, often requiring aggressive surgical resection. The pathobiology of this tumor remains poorly understood, and few models exist that are suitable for preclinical testing. The aim of this study was to establish new cell lines to serve as models for pathobiological and drug testing. With patient consent, freshly resected tumor tissue was cultured using conditional reprogramming cell conditions. Standard techniques were used to characterize the cell lines in terms of overall growth, clonogenicity, apoptosis, and differentiation in vitro. Additional analyses including Western blotting, short tandem repeat (STR) profiling, and next-generation sequencing (NGS) were performed. Drug screening using mitomycin-C (MMC), 5-fluorouricil (5-FU), and 6-Diazo-5-oxo-L-norleucine (DON) were performed. JHH-SebCA01, JHH-SebCA02, and JHH-SebCA03 cell lines were established from two women and one man undergoing surgical resection of eyelid tumors. At passage 15, they each showed a doubling time of two to three days, and all could form colonies in anchorage-dependent conditions, but not in soft agar. The cells contained cytoplasmic vacuoles consistent with sebaceous differentiation, and adipophilin protein was present in all three lines. STR profiling confirmed that all lines were derived from their respective patients. NGS of the primary tumors and their matched cell lines identified numerous shared mutations, including alterations similar to those previously described in SebCA. Treatment with MMC or 5-FU resulted in dose-dependent growth inhibition and the induction of both apoptosis and differentiation. MYC protein was abundant in all three lines, and the glutamine metabolism inhibitor DON, previously shown to target high MYC tumors, slowed the growth of all our SebCA models. Ocular adnexal SebCA cell lines can be established using conditional reprogramming cell conditions, and our three new models are useful for testing therapies and interrogating the functional role of MYC and other possible molecular drivers. Current topical chemotherapies promote both apoptosis and differentiation in SebCA cells, and these tumors appear sensitive to inhibition or MYC-associated metabolic changes.

Competing Interests: Conflicts of interest None disclosed.

Purpose: To report the outcomes of platinum-based neoadjuvant chemotherapy (NACT) for eyelid and periocular sebaceous gland carcinoma (eSGC)., Methods: Retrospective study of 25 patients., Results: The mean age at presentation of eSGC was 59 years. The mean tumor basal diameter was 46 mm. By the 8th edition of AJCC classification, tumors belonged T2 (n = 2, 8%), T3 (n = 6, 24%), and T4 (n = 17, 68%); N1 (n = 12,48%); and M1 (n = 1, 4%). NACT with 5-fluorouracil (5-FU) and cisplatin/carboplatin was administered in 21 (84%)/4 (16%) patients, respectively. The mean number of cycles of neoadjuvant systemic chemotherapy per patient was 2 (median, 3). The mean percentage reduction of tumor basal volume after neoadjuvant chemotherapy was 65% (median, 60%). After NACT, 12 (48%) patients underwent surgical treatment, 6 (12%) patients underwent EBRT, and 4 (8%) underwent adjuvant chemotherapy. A total of 11 (44%) patients were lost to follow-up during the course of treatment, of whom 3 died from metastatic disease. In 16 patients followed up for ≥ 3 months, complete tumor control was achieved in 11 (69%) patients, local tumor control in 14 (88%), and globe salvage in 7 (44%) at a mean follow-up of 25 months (median, 7 months; range, 3 to 110 months). No tumor recurrence was seen in any case. One (4%) serious adverse event of cardiotoxicity was noted., Conclusion: Platinum-based NACT is a suitable option for eSGC with advanced tumors and locoregional metastasis. Adverse events are rare and in patients compliant with treatment, NACT-based combination therapy offers globe salvage and systemic tumor control., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Here we present the first case of sebaceous carcinoma of the middle ear. We discuss the treatment course and post treatment results after 11 years of follow up. We further summarize the available literature of sebaceous carcinoma of the temporal bone, which prior to this case was exclusively limited to the external auditory canal. Laryngoscope, 134:3769-3772, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Purpose: Local recurrence predicts dismal prognosis in eyelid sebaceous carcinoma (SC). Recurrence predictors vary across studies. Accurate recurrence estimation is essential for individualized therapy in eyelid SC. This study aims to identify recurrence predictors and develop a nomogram for personalized prediction in eyelid SC., Methods: We conducted a multicenter retrospective cohort study. Chart reviews were performed in 418 consecutive patients with eyelid SC. All patients were followed up after their initial surgery. Multivariate Cox regression was used to explore the independent predictors of recurrence. A nomogram for recurrence prediction was developed and validated with bootstrap resampling. The predictive accuracy and discriminative ability were compared with the Tumor, Node, Metastasis (TNM) staging system., Results: Over a median of 60-month follow-up, 167 patients (40%) had local recurrence. The median time from diagnosis to recurrence was 14 months. The 1-year cumulative recurrence rate was 18%. Diagnostic delay (hazard ratio [HR] = 1.01, 95% confidence interval [CI] = 1.00-1.01, P = 0.001), orbital involvement (HR = 4.47, 95% CI = 3.04-6.58, P < 0.001), Ki67 (HR = 1.01, 95% CI = 1.00-1.02, P = 0.008) and initial surgery of Mohs micrographic surgery with intraoperative frozen section control (HR = 0.53, 95% CI = 0.35-0.80, P = 0.003) were independent influencing factors of recurrence. A nomogram integrating these four factors combined with pagetoid spread displayed satisfactory discriminative ability (C-index = 0.80-0.83; area under the curve [AUC] = 0.82-0.84), which compared favorably than TNM staging (all P < 0.05)., Conclusions: The recurrence rate is high in eyelid SC. Early detection and primary resection with Mohs micrographic surgery are recommended in controlling recurrence. Patients with orbital involvement, high Ki67 expression, and pagetoid spread may require adjuvant measures. This nomogram offers more accurate recurrence estimates, aiding in therapeutic decision making.

Sebaceous carcinoma is a known mimicker of benign conditions, leading to frequent delays in diagnosis and proper treatment. We present two patients with chronic cicatrizing conjunctivitis initially diagnosed as ocular mucous membrane pemphigoid (MMP) and later found to have sebaceous carcinoma. Both patients presented with unilateral conjunctivitis that failed to improve with topical and systemic therapy, eventually developing fornix foreshortening and extensive symblepharon. Case 1 was diagnosed with ocular MMP based on clinical features alone, while Case 2 was diagnosed with biopsy-negative disease. Months to years later, both patients developed lid lesions found to be sebaceous carcinoma and underwent exenteration. As diagnosis and treatment of ocular MMP without positive direct immunofluorescence testing becomes increasingly accepted, clinicians should consider sebaceous carcinoma as the initial diagnosis or as a developing phenomenon during immunosuppression in the setting of chronic inflammation. A low threshold for repeat biopsy should be maintained.

Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Introduction: Sebaceous gland carcinoma (SGC) of the eyelid is an aggressive tumour with the ability to metastasise and an increased morbidity. Controversies regarding the epidemiology of this malignant eyelid tumour is widespread in the scientific literature. Western reports repeatedly describes eyelid SGC as a rare occurring tumour in general, accounting for 1%-3% of all eyelid tumours, however studies from Asia have uncovered a higher frequency of eyelid SGC including 54% of all eyelid tumours in Japan, and 43%-56% in India. We wish to retrieve observational data of eyelid SGC prevalence in proportion to total eyelid tumours, from pathological studies published worldwide to resolve this controversy., Methods and Analysis: We will search Ovid Medline, EMBASE, Cochrane Central Register of Controlled Trials, Scopus and Google Scholar to identify published reports on eyelid SGC prevalence proportions, aiming to clarify the incidence of the tumour. We will include observational clinicopathological studies reporting prevalence with confirmed histopathology. No limitations on publication date or language will be applied. Data from the individual studies and study quality will be extracted by two individual reviewers. Study quality will be assessed using the JBI Critical Appraisal Instrument for Studies Reporting Prevalence Data. Raw proportions will be transformed and pooled using a random effects model for meta-analysis. And subgroup analysis according to geography will be performed. If data are deemed unsuitable for a meta-analysis, a narrative synthesis will be presented. We will judge the certainty of evidence and present whether this has an overall effect on the results. The results may shed light on a long-standing academic disparity of the scientific literature., Ethics and Dissemination: This systematic review does not require ethical approval. The results of this proposed review will be the subject to a publication in an international peer-reviewed journal within the ophthalmic or pathological specialty., Prospero Registration Number: CRD42023487141., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Ovarian mature teratomas (OMTs) originate from post-meiotic germ cells. Malignant transformation occurs in approximately 1-2% of OMTs; however, sebaceous carcinoma arising from OMTs is rare. This is the first report of a detailed genomic analysis of sebaceous carcinoma arising from an OMT. A 36-year-old woman underwent evaluation for abdominal tumors and subsequent hysterectomy and salpingo-oophorectomy. Pathologically, a diagnosis of stage IA sebaceous carcinoma arising from an OMT was established. Eight months post-surgery, the patient was alive without recurrence. Immunohistochemically, the tumor was negative for mismatch repair proteins. A nonsense mutation in TP53 (p.R306*) and a deletion in PIK3R1 were identified. Single nucleotide polymorphisms across all chromosomes displayed a high degree of homozygosity, suggestive of uniparental disomy. Herein, the OMT resulting from the endoreduplication of oocytes underwent a malignant transformation to sebaceous carcinoma via TP53 as an early event and PIK3R1 as a late event.

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., (© 2024 Wiley Periodicals LLC.)

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., (© 2024 the International Society of Dermatology.)

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., (© 2024 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by Wiley‐VCH GmbH on behalf of Deutsche Dermatologische Gesellschaft.)

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., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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., (© 2024. The Author(s).)

A 60-year-old female presented with a large, left upper eyelid mass that had rapidly expanded in the 3 months prior to presentation. She had a presumed chalazion excised from the same area 1.5 years ago, but no pathology was investigated. On examination, she had a palpebral mass measuring 4.5 cm x 3.5 cm that abutted the globe with extensive conjunctival involvement. Neuroimaging demonstrated lesions concerning for parotid gland metastases. An incisional biopsy demonstrated synaptophysin-positive small blue cells concerning for neuroendocrine carcinoma. The patient underwent orbital exenteration with parotidectomy and radical neck dissection. The excised mass was found to have distinct neuroendocrine carcinoma cells intermingled with sebaceous carcinoma cells, a combination not previously reported.

Primary sebaceous and lipid-rich carcinomas are extremely rare. Sebaceous carcinoma cells are large and oval with light, partially vacuolated cytoplasm. The second population consists of cells located mainly on the peripheral parts of tumour beaches. Those cells are of smaller calibre and are fusiform in appearance. Lipid- rich carcinoma is made up of multiple cell populations. The predominant cell type is with a distinctly light, vacuolated, and partially optically clear cytoplasm. Pathohistological analysis may be overlapping. On one side there is a tumour with a relatively excellent prognosis, and on the other, a highly aggressive carcinoma with a tendency for early metastases.

Sebaceous carcinoma (SC) is a very rare and aggressive form of skin cancer that arises from the sebaceous glands. SC can occur anywhere on the body, but most commonly affects the head and neck, especially the upper eyelid. SC is the third most common malignancy of the eyelid and has the potential to metastasize and be fatal; therefore, it is vital for dermatologists to remain acquainted with this malignancy and its most current treatment options. Most commonly presenting as a painless lump or thickening of skin on the eyelid, SC has an insidious progression that may not prompt the patient to seek medical attention immediately. To avoid the potential of metastasis, early diagnosis and treatment is paramount. To assess if the cancer has spread, ophthalmology, imaging, and sentinel lymph node biopsy are recommended. This article provides a comprehensive review of SC's pathogenesis, current diagnostic methods, and treatments, including wide local excision, Mohs micrographic surgery, orbital exenteration, radiation, and other topicals. The prognosis of SC depends on several factors, including size, location, stage, and treatment method. After treatment of the neoplasm, diligent post-treatment surveillance remains the cornerstone of patient care. Continued dermatologic follow-ups are essential for early detection of reoccurrence, ensuring timely intervention and optimal long-term outcomes. In conclusion, this comprehensive review aims to equip dermatologists and other physicians with a nuanced understanding of SC, enabling them to provide effective care to support patients encountering this malignancy., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Sebaceous carcinoma (SC) is a rare, potentially recurrent, and life-threatening cutaneous malignancy that can be associated with Muir-Torre syndrome (MTS), a DNA mismatch repair-driven genodermatosis. Earlier studies examining factors associated with recurrence have focused on periocular tumors only., Objective: Examine outcomes of SC and identify factors associated with recurrence., Materials and Methods: Retrospective study from 2 tertiary care centers., Results: Sixty-seven cases from 63 patients were identified, including 7 cases of MTS and 13 arising in the context of immunosuppression. Fifty-five cases (82.1%) were treated with complete circumferential peripheral and deep margin assessment (CCPDMA) methods. Five recurrences developed during the postoperative period. On univariate analysis, periocular location (odds ratio [OR] 7.6, p = .0410), and lesion size ≥2 cm (OR 9.6, p = .005) were associated with recurrence, whereas CCPDMA (OR 0.052, p = .0006) was inversely associated with recurrence. On multivariate analysis, only lesion size ≥2 cm (OR 9.6, p = .0233) and CCPDMA approaches (OR 0.052, p = .007) were significant., Conclusion: Non-complete circumferential peripheral and deep margin assessment methods and large lesion size were independent risk factors predicting recurrence, whereas anatomic subtype and MTS status were not. These findings can assist in identifying SC cases that may benefit from more aggressive treatment and closer surveillance., (Copyright © 2023 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Personalized medicine aims to develop tailored treatments for individual patients based on specific mutations present in the affected organ. This approach has proven paramount in cancer treatment, as each tumor carries distinct driver mutations that respond to targeted drugs and, in some cases, may confer resistance to other therapies. Particularly for rare conditions, personalized medicine has the potential to revolutionize treatment strategies. Rare cancers often lack extensive datasets of molecular and pathological information, large-scale trials for novel therapies, and established treatment guidelines. Consequently, surgery is frequently the only viable option for many rare tumors, when feasible, as traditional multimodal approaches employed for more common cancers often play a limited role. Sebaceous carcinoma of the eyelid is an exceptionally rare cancer affecting the eye's adnexal tissues, most frequently reported in Asia, but whose prevalence is significantly increasing even in Europe and the US. The sole established curative treatment is surgical excision, which can lead to significant disfigurement. In cases of metastatic sebaceous carcinoma, validated drug options are currently lacking. In this project, we set out to characterize the mutational landscape of two sebaceous carcinomas of the eyelid following surgical excision. Utilizing available bioinformatics tools, we demonstrated our ability to identify common features promptly and accurately in both tumors. These features included a Base-Excision Repair mutational signature, a notably high tumor mutational burden, and key driver mutations in somatic tissues. These findings had not been previously reported in similar studies. This report underscores how, in the case of rare tumors, it is possible to comprehensively characterize the mutational landscape of each individual case, potentially opening doors to targeted therapeutic options.

Sebaceous carcinoma (SC) is a malignant neoplasm demonstrating sebocytic differentiation, commonly in the periocular area. Sebocytic differentiation is recognized by multivesicular cytoplasmic clearing with frequent nuclear scalloping. The vesicles can be highlighted by immunohistochemical stains against the perilipin family proteins including adipophilin. Extraocular SC is uncommon but well reported, often in the setting of Muir-Torre syndrome; however, vulvar SC is exceptionally rare. The literature review yielded only 12 prior cases of vulvar SC, all of which showed invasion. Here we report 2 additional similar cases from 2 different institutions of an intraepithelial carcinoma with sebaceous differentiation. Histologic examination of multiple specimens from both patients showed similar features: a multifocal intraepithelial basaloid nodular neoplasm sparing the basal layer with occasional pagetoid spread. The tumor cells demonstrated a high nuclear to cytoplasmic ratio, mitoses, variably foamy vacuolated cytoplasm, and nuclear indentation. Multiple specimens from both patients showed evidence of sebaceous differentiation (substantiated by adipophilin positivity in a membranous vesicular pattern in case 1 and by androgen receptor and epithelial membrane antigen positivity in case 2), and squamous differentiation (substantiated by p63/p40 and weak CK 5/6 expression), as well as human papillomavirus (HPV) association (substantiated by p16 block positivity and detection of high-risk HPV by in situ hybridization). One case was a true in situ lesion without evidence of invasion, and the other case was predominantly an in situ carcinoma with prominent adnexal extension and focal superficial invasion of <1 mm seen in one of multiple specimens. To our knowledge, these 2 cases are the first to show a vulvar SC/carcinoma with sebaceous differentiation that is predominantly limited to the epidermis, and the first documentation of HPV infection in vulvar sebaceous neoplasms. Vulvar intraepithelial carcinoma with sebaceous differentiation is the umbrella term we chose for this entity. Whether this is a true SC in situ that is HPV positive/driven, or a vulvar intraepithelial neoplasia with sebaceous differentiation, is not entirely clear. We emphasize the importance of looking for this morphology to avoid misclassification. Due to the rarity of cases, optimal treatment at this site has not been established., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 by the International Society of Gynecological Pathologists.)

Caruncle malignancy is rare, but signs of disease can be easily missed by both patients and clinicians. There is significant potential for significant morbidity and even mortality from delayed diagnosis and treatment. Clinical features of primary malignant cancer include rapid growth, pigment deposition, ulcerated surface and bleeding. Malignant diagnoses include lymphoproliferative disease, basal cell carcinoma, squamous cell carcinoma, sebaceous carcinoma and malignant melanoma. Increased pigmentation is associated with melanoma, yellow coloured deposition with sebaceous carcinoma and a salmon-pink hue with lymphoproliferative disease. Treatment involves excision with margin control which may necessitate exenteration. Metastases to cervical and preauricular lymph nodes has been reported., (© 2022. Crown.)

Aims: To determine the distribution of three different intraepithelial growth patterns (pagetoid, bowenoid and papillary) in eyelid sebaceous carcinoma (SC) and correlate them with the clinical characteristics and prognosis., Methods: A retrospective cohort study. The medical charts and pathological sections were retrospectively reviewed. All eligible patients were followed up for recurrence, metastasis and tumour-related mortality. The clinical significance of each intraepithelial growth pattern was determined by Cox regression., Results: Of the 214 patients, 67 (31%) presented with intraepithelial invasion, among them, 34 (16%) were pagetoid, 27 (13%) were bowenoid and 6 (2.8%) were papillary. Patients of pagetoid intraepithelial spread showed significantly longer diagnostic delay (p=0.001) and more initial misdiagnoses of blepharitis (p=0.035). After a median follow-up period of 34.0 months, 67 (46%) patients in the non-intraepithelial group, 17 (50%) in the pagetoid group, 8 (30%) in the bowenoid group and 2 (33%) in the papillary group recurred. And 30 (20%) patients in the non-intraepithelial group, 9 (27%) in the pagetoid group and 4 (15%) in the bowenoid group developed metastasis. Moreover, 15 (10%) patients in the non-intraepithelial group, 6 (18%) in the pagetoid group and 1 (3.7%) in the bowenoid group died of SC. Cox regression indicated that pagetoid intraepithelial growth pattern was remarkably associated with increased chances of tumour-related mortality (HR=2.95, 95% CI 1.14 to 7.64, p=0.026)., Conclusions: Intraepithelial tumour invasion was presented in nearly one third of patients with eyelid SC. Pagetoid intraepithelial neoplasia, the predominant growth pattern, significantly increased the risk of tumour-related mortality. Meticulous histopathological intraepithelial examination is recommended for every patient of eyelid SC. Special attention should be paid to those with pagetoid invasion, who may require more intensive managements., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Mohs micrographic surgery (MMS) for sebaceous carcinoma (SC) may reduce local recurrence rates, but published case series have small cohorts and limited follow-up. Mohs micrographic surgery is particularly suitable for sensitive functional and cosmetic locations, such as the face, because it facilitates tissue conservation using complete peripheral and deep margin assessment before reconstruction. Coordinated care between Mohs and oculoplastic surgeons has not been described., Objective: To assess rates of local recurrence and metastasis after MMS of facial SC and to describe coordinated care between Mohs and oculoplastic surgeons., Materials and Methods: Retrospective review identified facial SC cases treated with MMS at a single institution from January 2005 to August 2020. Tumor characteristics and outcomes were recorded. Descriptive and predictive analyses were performed., Results: Forty-nine cases were reviewed with a mean follow-up of 51 months. The most common sites were periorbital, infraorbital cheek, and nasal ala. No patients experienced regional recurrence after MMS. One patient with Muir-Torre syndrome developed metastatic recurrence (at 82.9 months). All patients underwent 2-stage reconstruction with dermatology-performed MMS and oculoplastic reconstruction., Conclusion: Collaboration between Mohs and oculoplastic surgeons with a tissue-sparing approach of MMS can reduce recurrence and optimize cosmesis and function for central facial SC., (Copyright © 2022 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Aims: Clear cells formed due to depositions of glycogen or lipids in the cytoplasm commonly occur in various tissues. Adipophilin (ADP), a lipid regulatory protein, is closely related to lipid droplets. This study aims to examine adipophilin expression in clear cells of various skin lesions., Methods: ADP expression was examined using immunohistochemistry in 108 sections from 15 skin lesion types with clear cell histology, namely, sebaceoma (n=16), sebaceous adenoma (n=3), sebaceous carcinoma (n=12), xanthomata cutis (n=10), xanthogranuloma (n=8), Paget's disease (n=10), Bowen disease (n=10), hidradenoma (n=9), atypical lipoma (n=5), superficial lipomatous nevus (n=5), metastatic renal cell carcinoma (n=5), squamous cell carcinoma (n=4), seborrheic keratosis (n=4), dermatofibroma (n=4) and clear cell sarcoma (n=3)., Results: ADP was not expressed in Bowen disease, hidradenoma or seborrheic keratosis. Four expression patterns, foamy, reticular, granular and punctate, were summarised based on their expression in clear cells. Different expression patterns were related to tissue origin and differentiation degree. Foamy expression was commonly observed in lesions with mature sebaceous glands and xanthomas; reticular expression in adipocytes; granular expression in xanthoma, xanthogranuloma and metastatic renal carcinoma and punctate expression in sebaceoma, sebaceous carcinoma, Paget's disease, squamous cell carcinoma and clear cell sarcoma. Furthermore, stronger staining with focal vesicular labelling was noted in sebaceoma than in sebaceous carcinoma. Characteristic labelling was noted, including the circular distribution in Touton giant cells of xanthogranulomas and focal distribution in the clear cells along the edge of necrotic tissue in clear cell sarcoma., Conclusions: ADP is useful in identifying intracytoplasmic lipids and can be used to diagnose skin lesions with clear cell histology, especially in some lesions with characteristic labelling., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Collision tumors are rare clinical entities that two heterogeneous neoplasms are concurrently adjacent to each other at the same location. The association of a squamous cell carcinoma and a malignant adnexal tumor is even infrequent., Case Presentation: The case of a 79-year-old woman having a slow-growing and painless tumor on the left lower eyelid was presented. The lesion, about 15 mm in diameter, was nodular, irregular, and yellow-discolored. Histopathologic and immunohistochemical findings disclosed concurrence of sebaceous carcinoma as well as squamous cell carcinoma in one specimen. Wide excision of the tumor with frozen section control and eyelid reconstruction were performed. Oncologic survey revealed no other lesion. At 6-month follow-up, no evidence of recurrence or metastasis was presented., Conclusion: Collision tumor composed of sebaceous carcinoma and squamous cell carcinoma in eyelid may be the first case described in the literature. For increasing accuracy of diagnosis and management, a thorough clinical examination and detailed histopathologic analysis, along with multidisciplinary discussion, are prerequisites.

Background: Sebaceous adenocarcinoma (SAC) mostly occurs in the elderly, and SAC in young and middle-aged population is inadequately investigated., Objective: To explore the clinical features and prognosis of young and middle-aged adults with SAC., Materials and Methods: Patients with skin SAC between ages 18 and 59 years from the Surveillance, Epidemiology, and End Results database (1975-2016) were eligible for this study., Results: Seven hundred thirty-nine cases were identified. The proportion of extraocular SAC in the nonelderly increased from 1975-2005 to 2006-2016 ( p = .001), male predominance was observed in overall patients whereas female predominance in Asian population, and young patients had more head and neck SAC than middle-aged patients ( p = .014). The prognosis of young patients was better than middle-aged patients ( p = .004). Other independent prognostic factors included sex, marital status, tumor size, surgery, chemotherapy, and multiple primary cancer history., Conclusion: An increasing proportion of extraocular SAC was observed in young and middle-aged patients, and the young developed more head and neck SAC than the middle-aged. Female predominance was found in Asian population, and female patients had better prognosis. Younger age and married status indicated better prognosis, and around 20% of young and middle-aged patients might have poorer survival because of Muir-Torre syndrome., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society for Dermatologic Surgery, Inc.)

Sebaceous carcinoma (SC) is a rare malignant neoplasm with sebaceous differentiation. SC is classified into eyelid and extraocular SC clinically. Most studies have focused on the eyelid SC in terms of pathogenesis, treatment, and prognosis. In skin, Wnt/beta-catenin and hedgehog signaling are two major pathways in sebaceous differentiation. We aimed to characterize the clinical and histopathological features of extraocular SC and to measure the expression of beta-catenin, lymphoid enhancer-binding factor 1 (LEF1), sonic hedgehog (Shh), and protein patched homolog 1 (PTCH) in extraocular SC. Ten cases of extraocular SC were identified from 2007 to 2020. The clinical features, microscopic findings, and prognosis were analyzed. Immunohistochemical stain for beta-catenin, LEF1, Shh, and PTCH were performed in extraocular SC and other benign sebaceous tumors including sebaceous hyperplasia, sebaceous adenoma, and sebaceoma. The male:female ratio was 4:6. The median onset age was 73.5 years (range, 43-88). Seven patients out of 10 were diagnosed after 60 years. Most extraocular SC were located on the head and neck with indurated plaque. Two patients had concurrent internal cancers and three patients showed lymph node metastasis at time of presentation. Five-year overall-survival was 40%. Beta-catenin was expressed membranously in all sebaceous hyperplasia, but was expressed variably in extraocular SC (1/5). While LEF1 was unequivocally expressed in normal hair follicles, LEF1 expression was absent in all extraocular SC and benign sebaceous tumors. Regarding the sonic hedgehog signaling, Shh and PTCH were all expressed in the cytoplasm of sebaceous hyperplasia, sebaceous adenoma, and sebaceoma. In contrast, PTCH was absent in all cases of extraocular SC and only 50% of the extraocular SC expressed cytoplasmic Shh. To conclude, extraocular SC commonly affects facial skin in the elderly. Inactivated Wnt/beta-catenin and aberrant hedgehog pathway may contribute to the carcinogenesis of extraocular SC. Further studies may be required to elucidate the causative mechanism of these pathways in extraocular SC., (© 2022 Japanese Dermatological Association.)

Background: Sebaceous carcinoma is an aggressive malignant tumour. To prevent mutilating surgery and improve patient outcomes, early diagnosis and prompt treatment are necessary. When the tumour invades surrounding tissues, treatment may become complex., Methods: We present a case report illustrating complex resection and reconstruction of a sebaceous carcinoma after initial misdiagnosis., Results: A 74-year-old man with a sebaceous carcinoma to his right upper eyelid had a delay in treatment due to initial misdiagnosis. Upon the correct diagnosis, computed tomography scan showed tumour invasion of the medial rectus muscle and tumour spread to the right parotid gland. An orbital exenteration, partial parotidectomy and selective cervical lymphadenectomy were performed. Frozen section examination showed false-free margins, as additional paraffin embedded sections showed uncomplete tumour resection. Adjuvant radiotherapy was offered to the patient. The treatment was complicated by radio necrosis, necessitating surgical reconstruction by a paramedian forehead flap. Final reconstruction of the right orbit was accomplished by a personalised epithesis., Conclusions: Sebaceous carcinoma is a tumour that is often misdiagnosed. The aim of this case report is to emphasize the possible consequences of its misdiagnosis. An overview of characteristic clinical findings is provided to help reduce the number of misdiagnoses.

Introduction: Sebaceous carcinoma is a rare malignant tumor of the sebaceous glands. Sebaceous carcinoma occurs mainly in the head and neck region, rarely in trunk.  Case report: We present a case report of 63-year-old patient, operated on for sebaceous carcinoma in the right breast area. The patient underwent radical surgery, removal of the tumor with the skin, subcutaneous tissue, and the large pectoral muscle. The patient is in good clinical condition eight months after the surgery. She is being constantly monitored and so far, there are neither signs of local recurrence nor tumor progression.  Conclusion: Patients with rare tumors should be treated comprehensively with subsequent lifelong dispensarisation in specialized centers. Multidisciplinary medical teams are able to eruditely diagnose, recognize, treat and dispense patients.

Background: Immunohistochemistry for preferentially expressed antigen in melanoma (PRAME) has been studied in melanocytic lesions but not nonmelanoma skin cancers (NMSCs). This study evaluated PRAME expression in NMSCs and dermoepidermal junction (DEJ) melanocytes in the surrounding skin., Methods: Ninety-nine NMSCs were studied: 23 Merkel cell carcinomas (MCCs), 25 well to poorly differentiated squamous cell carcinomas (SCCs), 14 basal cell carcinomas (BCCs), five basosquamous carcinomas, four sebaceous carcinomas, ten atypical fibroxanthomas, 11 dermatofibrosarcoma protuberans, and seven leiomyosarcomas. Staining quality was considered low or high intensity. Staining quantity was reported as negative 0%, 1% to 24%, 25% to 50%, and >50%. DEJ melanocyte PRAME expression was recorded., Results: Forty-eight percent of NMSCs showed PRAME expression, mostly low intensity in fewer than 25% of cells. High-intensity expression was noted in one poorly differentiated SCC, six BCCs, and seven MCCs. Only MCCs showed expression in greater than 25% of tumor cells. Focal DEJ melanocytes expressed high-intensity PRAME in 18% of cases, most commonly SCCs (11/23)., Conclusions: PRAME is negative or expressed with low intensity in a small percentage of NMSCs, with the exception of some MCC showing high-intensity and diffuse staining. Focal DEJ melanocytes showed high-intensity PRAME reactivity in the skin surrounding some NMSCs., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Epithelial-myoepithelial carcinoma (EMCA) is a rare low-grade carcinoma of the salivary glands with multiple morphological variants. One such variant, sebaceous EMCA (SEMCA), has been reported in the literature. Distinguishing it from other tumors such as sebaceous carcinoma is crucial, as SEMCA typically behaves more indolently. We present a case of a SEMCA in the right parotid of a 71-year-old man that shows features of aggressive behavior such as facial nerve invasion and extraparenchymal extension. Also, we report evidence of preexisting pleomorphic adenoma within this tumor.