Extraocular Sebaceous Carcinoma Research Articles

S1‐Leitlinie Talgdrüsenkarzinom

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 system therapies such as chemotherapy or immunotherapy can be considered. The procedure should be determined individually in an interdisciplinary tumor board. Close follow-up care is recommended for these potentially aggressive carcinomas.

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.

Extra-Ocular Sebaceous Carcinoma in Situ of the Arm of an Elder Male: An Unusual Presentation in an Atypical Location.

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.

Extra-Ocular Sebaceous Carcinoma Unveiled: A Case Study of Dermal Challenges in an Elderly African American Patient

Extra-Ocular Sebaceous Carcinoma Unveiled: A Case Study of Dermal Challenges in an Elderly African American Patient

DP18 Extraocular sebaceous carcinoma in situ

Abstract Extraocular sebaceous carcinoma in situ (SCIS) is exceedingly rare with < 10 cases reported in the literature (Jeong KM, Seo JY, Kim A et al. Extraocular sebaceous carcinoma in situ concurrent with actinic keratosis: a case report and review of the literature. Korean J Dermatol 2021; 59:307–9). An 80-year-old man reported a 3-month history of a right forehead lesion that had been bleeding. This was a subtle 5 × 5 mm papule on clinical examination, and dermoscopy showed arborizing telangiectasia. Past medical history was significant for 20 basal cell carcinomas, one squamous cell carcinoma, Bowen disease and actinic keratoses. Histology showed sun-damaged skin with a partially eroded neoplasm of lobular architecture, with surface and infundibular epithelium containing atypical sebocytes and squamous cells with no infiltrative growth pattern, which was consistent with SCIS and was fully excised. Immunohistochemistry revealed patchy adipophilin and androgen receptor staining and stronger epithelial membrane antigen staining. Furthermore, there was preserved expression of MSH2, MSH6, MLH1 and PMS2. Sebaceous carcinoma in situ is a debated entity not formally recognized in the classification of sebaceous neoplasms. Kazakov et al. reported five cases of dermal sebaceous tumours with ‘benign’ architectural features (well-circumscribed and no evidence of invasion) but with cytological atypia (abnormal mitoses and pleomorphism) (Kazakov D, Kutzner H, Spagnolo DV et al. What is extraocular cutaneous sebaceous carcinoma in situ? Am J Dermatopathol 2010; 32:857–8). The authors questioned whether these cases represented sebaceous adenomas with atypia or sebaceous carcinomas (Kazakov et al.). In response, it has been argued that such architectural–cytological discordant tumours can be regarded as SCIS owing to the fact that, by definition, carcinoma in situ is a cancer that remains wholly at the site of origin. However, it is argued that these lesions have an unclear origin and may not arise from sebaceous glands in the skin, unlike the more common aggressive periorbital sebaceous carcinomas that arise from meibomian glands and glands of Zeis (Kazakov et al.). It has been postulated that a SCIS diagnosis should be reserved for intraepidermal tumours not extending beyond the epidermal basement membrane, which is a vanishing minority of sebaceous neoplasms (Kazakov et al.). Similar to our case, a 2021 case report identified SCIS without any connection to an adnexal component but concurrent with actinic keratosis. These authors proposed that the tumour cells of intraepidermal squamous neoplasia can differentiate towards malignant sebocytes (Jeong et al.). Although controversial, SCIS appears to have reasonable, clear histological criteria for diagnosis and an excellent prognosis, with no reports of recurrence following surgical excision. We feel it is important to increase identification to avoid the overtreatment of such lesions.

Ocular and extraocular sebaceous carcinomas: A retrospective study with emphasis on the presence of insitu lesion and discussion and review of the histogenesis of extraocular sebaceous carcinoma.

Sebaceous carcinoma (SC) is a rare carcinoma classified as ocular or extraocular. Ocular SC is believed to arise from the meibomian glands or the glands of Zeis. However, the origin of extraocular SC is controversial because there is no evidence of carcinoma arising from pre-existing sebaceous glands. Several hypotheses about the origin of extraocular SC have been proposed, including one suggesting an origin from intraepidermal neoplastic cells. Although extraocular SCs have been shown to occasionally comprise intraepidermal neoplastic cells, no study has investigated whether intraepidermal neoplastic cells possess sebaceous differentiation. The present study analyzed the clinicopathological features of ocular and extraocular SC, with an emphasis on the presence of in situ (intraepithelial) lesions. It retrospectively reviewed the clinicopathological features of eight patients with ocular and three patients with extraocular SC (eight women and three men; median age, 72 years), respectively. In situ (intraepithelial) lesions were observed in four of the eight ocular SC cases and one of the three extraocular SC cases and an apocrine component was noted in one patient with ocular SC (seboapocrine carcinoma). In addition, immunohistochemical analyses showed that the androgen receptor (AR) was expressed in all ocular SCs and two of the three extraocular SC cases. Adipophilin expression was observed in all ocular and extraocular SC. In situ lesions of extraocular SC showed positive immunoreactivity for both AR and adipophilin. The present study is the first to demonstrate sebaceous differentiation in in situ lesions of extraocular SC. The possible origin of extraocular SC is speculated to be the progenitor cells present in the sebaceous duct or interfollicular epidermis. The results of the present study and reported cases of SC in situ indicate that extraocular SC also arises from intraepidermal neoplastic cells.

Orbital Adnexal Malignant Tumours: A Report of Two Cases

Sebaceous carcinoma of the eyelid is a very rare malignant tumour, accounting for 1-1.5% of total eyelid malignancies. It typically arises from the meibomian glands, making it more common in the upper eyelids. It predominantly affects individuals in their sixth to eighth decade, with a higher incidence in females. Histologically, the tumour cells are arranged in well-defined lobules with circumscribed borders. These cells exhibit pleomorphism, eccentric hyperchromatic nuclei, inconspicuous nucleoli, and multivacuolated cytoplasm. The clinical course of sebaceous carcinoma is aggressive, often characterised by recurrences and metastasis to regional lymph nodes. Unfortunately, it is not commonly considered in the differential diagnosis of eyelid tumours, leading to delayed treatment. Thus, it is crucial to raise awareness about this uncommon neoplasm occurring at unusual sites in order to improve patient survival. In the present case report, the authors present two cases: a 54-year-old male patient with intraocular sebaceous carcinoma, which recurred, and an 83-year-old male patient with extraocular sebaceous carcinoma. In both the cases, imaging and other investigations were performed, followed by excision of the mass and confirmation of the diagnosis through histopathological reporting. Subsequent follow-up was conducted for both cases and the postoperative recovery was uneventful.

Radiotherapy With Hydrogen Peroxide-Soaked Gauze for Preauricular Sebaceous Carcinoma

Sebaceous carcinoma is a rare and aggressive malignant tumor deriving from the adnexal epithelium of the sebaceous glands. The case of inoperable preauricular sebaceous carcinoma treated with definitive radiotherapy is first reported herein. Radiotherapy of 60 Gy in 30 fractions was combined with a hydrogen peroxide-soaked gauze bolus aiming at potential radiosensitization. Macroscopic complete remission was achieved eight months after radiotherapy with tolerable adverse effects. Although further clinical studies are needed, radiotherapy with a hydrogen peroxide-soaked gauze bolus can be an effective and tolerable treatment for inoperable patients with extraocular sebaceous carcinoma.

Yield of sentinel lymph node biopsy in sebaceous carcinoma and predictors of advanced disease: A retrospective analysis of the National Cancer Database

To the Editor: Sebaceous carcinoma (SC) is a rare cutaneous malignancy with potential for lymph node or distant metastasis. Most SC presents as localized disease, but periocular SC manifests distinct tumor behavior from extraocular SC with a greater propensity for metastasis. Present guidelines suggest that American Joint Committee on Cancer, Eighth Edition stage T2c periocular or greater tumors can be considered for sentinel lymph node biopsy (SLNB), although SLNB is not recommended for extraocular SC because subclinical nodal metastasis is thought to be uncommon in this setting.

SEBACEOUS CARCINOMA OF AXILLA: A RARE CASE REPORT

Sebaceous carcinoma (SC) is a rare cutaneous malignant neoplasm. It is derived from the epithelium of sebaceous glands and thus, can occur anywhere in the body where these glands are found. SC are of two types: ocular and extraocular, with extraocular SC being rare and SC of axilla being very rare. The paper reports a case of 55-year-old male patient, with complain of swelling in the right axilla. The patient underwent wide local excision of the mass and the excised specimen was sent for histopathological (HPE) analysis, which showed features consistent with sebaceous carcinoma. The patient was planned for treatment with adjuvant chemotherapy, and is currently under treatment.

Impaired Wnt/beta-catenin and protein patched homolog 1 signaling in extraocular sebaceous carcinoma: A clinical and histopathological study.

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 73.5years (range, 43-88). Seven patients out of 10 were diagnosed after 60years. 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.

Extraocular sebaceous carcinoma: tumor presentation of rapid evolution

Extraocular sebaceous carcinoma: tumor presentation of rapid evolution

EP.WE.741Management of a giant extraocular sebaceous carcinoma during the COVID-19 Pandemic: a case report

IntroductionSebaceous carcinoma is a rare malignant skin tumour of the sebaceous glands which is most frequently located in the ocular region (75% of cases). Prompt recognition and treatment is vital, as it bears a high mortality rate ranging from 9 – 50%. We present a rare case of a giant sebaceous carcinoma of the upper back, managed as a day-surgery case because of resource and safety restrictions due to the COVID-19 pandemic.Case reportWe present a case of a 58-year-old male patient with a giant lesion on his upper back measuring 13 x 13cm in size. Due to the COVID-19 pandemic, this was resected under local anaesthetic. The histology and immunohistochemistry confirmed the diagnosis of a giant sebaceous carcinoma. Resection margins were clear and subsequent investigations confirmed there were no metastases. The defect was reconstructed with Matriderm © and a split-thickness skin graft, achieving a satisfactory cosmetic outcome at 3 months follow-up.ConclusionThis is the first report which demonstrates the wide local excision under local anaesthetic for a rare presentation of a giant sebaceous carcinoma. This approach may be more widely utilised in the extraocular manifestation of this tumour, reducing the morbidity and length of hospital stay for such patients.

Targeted Sequencing Revealed Distinct Mutational Profiles of Ocular and Extraocular Sebaceous Carcinomas.

Simple SummaryThe molecular pathogenesis of sebaceous carcinoma is largely unknown so far. The main aim of our study was to investigate genetic alterations in ocular and extraocular sebaceous carcinoma in Korean patients. By applying targeted next-generation sequencing, we demonstrated a distinct mutational profile in ocular and extraocular sebaceous carcinoma. In addition, clinically actionable variants involving tyrosine kinase genes and homologous recombination deficiency-associated genes were detected, suggesting the possibility of targeted therapeutic trials in intractable sebaceous carcinoma cases.The biological behavior of sebaceous carcinoma (SeC) is relatively indolent; however, local invasion or distant metastasis is sometimes reported. Nevertheless, a lack of understanding of the genetic background of SeC makes it difficult to apply effective systemic therapy. This study was designed to investigate major genetic alterations in SeCs in Korean patients. A total of 29 samples, including 20 ocular SeCs (SeC-Os) and 9 extraocular SeCs (SeC-EOs), were examined. Targeted next-generation sequencing tests including 171 cancer-related genes were performed. TP53 and PIK3CA genes were frequently mutated in both SeC-Os and SeC-EOs with slight predominance in SeC-Os, whereas the NOTCH1 gene was more commonly mutated in SeC-EOs. In clinical correlation, mutations in RUNX1 and ATM were associated with development of distant metastases, and alterations in MSH6 and BRCA1 were associated with inferior progression-free survival (all p < 0.05). In conclusion, our study revealed distinct genetic alterations between SeC-Os and SeC-EOs and some important prognostic molecular markers. Mutations in potentially actionable genes, including EGFR, ERBB2, and mismatch repair genes, were noted, suggesting consideration of a clinical trial in intractable cases.

Extraocular Sebaceous Carcinoma Treated With Mohs Micrographic Surgery-A 24-Year Retrospective Review of Tumor Characteristics and Treatment Outcomes.

Extraocular sebaceous carcinoma (SC) is rare, with distinct features from its ocular counterpart. These neoplasms have been associated with Muir-Torre syndrome (MTS). Associated internal malignancies include gastrointestinal and genitourinary. Assess for local recurrence, metastasis, disease-specific death, and additional malignancies in patients with extraocular SC treated with Mohs micrographic surgery (MMS) at a single referral center. Review of patients with extraocular SC treated with MMS between 1995 and 2019. Follow-up was obtained by chart review. Thirty-eight patients with 41 tumors were identified (25, 66% male). During a mean follow-up of 5.9 ± 5 years, one case of metastasis was identified in an incompletely treated case. No recurrence was identified in the remaining 40 tumors. Five of 41 (12%) tumors had aggressive histologic features. Seven of 38 (18%) patients had a diagnosis of MTS or associated risk factors. There was no association between MTS or its risk factors and high-risk tumors. There were no incidences of local recurrence, metastasis, or disease-specific death in cases treated completely with MMS. Metastasis and disease-specific death occurred in an incompletely treated case, highlighting the risk associated with aggressive tumors.

A Case Report: A Rare Case of Extraocular Sebaceous Carcinoma on the Chin in 22-Year-old Asian Young Man

A Case Report: A Rare Case of Extraocular Sebaceous Carcinoma on the Chin in 22-Year-old Asian Young Man

PD-L1 expression in sebaceous carcinomas.

Traditional systemic treatments for unresectable, recurrent, and/or advanced sebaceous carcinoma (SC) are ineffective. Tumoral immune microenvironment characterization is essential for considering immune checkpoint inhibitors as a treatment option. A total of 173 resected SCs were reviewed. Clinical information, lesion size, and location were collected. Microscopic examination documented histopathologic features and expression of immunohistochemical markers PD-L1 and CD8. PD-L1 percentage was assessed amongst tumor (PD-L1 + Tu) and immune infiltrating cells (PD-L1 + Inf). Each case was attributed a combined positive score (CPS) following Head and Neck squamous cell carcinoma recommendations. PD-L1 expression was evaluated according to clinicopathologic parameters. Human Papilloma Virus presence (HPV) was analyzed using PCR microarray scanning. A therapeutically relevant CPS was seen in 51.4% of cases. Higher PD-L1 + Tu, PD-L1 + Inf, and CPSs were positively associated with greater lesion size and an extraocular location. No association was seen with patient age or gender. 9.2% of SCs showed PD-L1 + Tu ≥ 1, while 52.0% showed PD-L1 + Inf ≥ 1. A higher CD8 + T-lymphocyte density was significantly associated with a higher CPS, PD-L1 + Tu, and PD-L1 + Inf. Tumor-associated T-cell infiltrate's density was higher along tumor periphery. HPV-16, HPV-43, HPV-52, and HPV-66 were detected in 8.4% of SCs. There was no significant association between HPV status, PD-L1 expression, and CPS. A significant number of SCs express PD-L1 at therapeutic levels. Nevertheless, PD-L1 expression shows a higher intertumoral heterogeneity, in extraocular than in biologically distinct periocular cases. Our data support the need for large-scale prospective studies evaluating anti-PD-L1 immunotherapy mainly in extraocular SC treatment.

Sebaceous carcinoma of the axilla

Sebaceous carcinoma is a rare cutaneous malignant neoplasm with an estimated incidence rate of approximately 1–2 per 1 000 000 per year. It rarely presents as an extra-ocular type and it affects patients in between the sixth and eighth decades of life. This is a case of a 31-year-old male with a 10-year history of a right axillary mass with an incisional biopsy of a sebaceous carcinoma. The mass was 10 × 6 cm in largest diameter, erythematous, non-tender and irregularly shaped. The patient underwent wide excision of the right axillary mass with negative margins confirmed by frozen section under general anesthesia. A parascapular fasciocutaneous flap was done in order to provide coverage for the defect. The patient was then discharged improved on the fourth postoperative day. Although there has been no established clinical protocol for the staging, medical and surgical management for extra-ocular sebaceous carcinoma, early diagnosis accompanied with the proper surgical intervention, such as oncologic wide excision with negative margins, were both adequate and paramount to the diagnosis, course and treatment of this patient, given its rarity.

Sebaceous Tumors of the Skin: A Study of 145 Lesions From 136 Patients Correlating Pathologic Features and DNA Mismatch Repair Staining Pattern.

Sebaceous neoplasms occur sporadically or in the setting of Muir-Torre syndrome. The data regarding the correlation of pathologic features and DNA mismatch repair (MMR) staining pattern in sebaceous tumors of the skin are very scanty and based on relatively small series of patients. The goal of this study was to correlate MMR staining pattern with selected morphological features in a series of 145 sebaceous neoplasms (sebaceous adenoma, sebaceoma, and extraocular sebaceous carcinoma) from 136 patients. Cystic change, intratumoral mucin deposits, squamous metaplasia in the absence of keratoacanthoma-like changes, ulceration, intratumoral and peritumoral lymphocytes (in cases without epidermal ulceration), and intertumoral heterogeneity proved to be significantly associated with MMR deficiency. Identification of any of these changes, alone or in combination, should prompt further investigation of the patient to exclude Muir-Torre Syndrome. Our study also confirms the previously published observation that the diagnosis and tumor location are significantly associated with MMR deficiency.

Twenty-Eight Cases of Extraocular Sebaceous Carcinoma: A Correlative Clinicopathological and Immunohistochemical Analysis of Extraocular Sebaceous Carcinomas and Benign Sebaceous Gland Tumors.

Extraocular sebaceous carcinoma (ESC) is a rare appendiceal skin tumor. In contrast to ocular sebaceous carcinoma, information about the exact cellular architecture of these lesions is scarce and the histogenesis of ESC is unknown. Here, we extend our previous study and investigate 28 extraocular carcinomas in comparison to 54 benign sebaceous tumors and 8 cases of normal sebaceous glands using a broad spectrum of antibodies against p63, several keratins, adipophilin, EMA, Ki67, androgen receptor, and mismatch repair proteins. This observational study demonstrates that p63- and K5/14-positive basaloid cells are key cells in normal sebaceous gland and in all sebaceous tumors and that these basaloid cells give rise to EMA+, adipophilin+ sebocytes, and K5/14+, K7±, K10± ductal structures. Finally, about half of ESC is associated with superficial in situ neoplasia, which provides evidence that at least part of these carcinomas arises from flat superficial in situ carcinoma. In contrast to the normal sebaceous gland, about half of all sebaceous tumors lack keratin K7. MMR protein IHC-profiles role will be discussed.