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.

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.

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.

Intraoral sebaceous carcinoma: A rare presentation on the tongue and review of the literature.

Intraoral sebaceous carcinoma (SC) is exceedingly rare, especially in the tongue. We reported the clinicopathological and immunohistochemical features of a rare SC case in a 59-year-old male who presented a painful ulcer on the tongue's posterior region. Microscopically, the tumor was composed of atypical basaloid cells with round to oval nuclei and prominent nucleoli arranged in lobes showing prominent sebaceous differentiation and areas of holocrine secretion. Immunohistochemistry showed positivity for pan-cytokeratin AE1/AE3 and epithelial membrane antigen (EMA) and negativity for cytokeratin 7 (CK7). The sebaceous cells were positive for adipophilin and perforin. Wide surgical excision followed by adjuvant chemotherapy and radiotherapy was performed. Careful histopathological analysis of these lesions is crucial to ensure a correct diagnosis. Due to the aggressive behavior of SCs, early diagnosis and treatment are essential to increase the patient's survival time. To the best of our knowledge, this is the second case of SC in the tongue.

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.

Sebaceous carcinoma: an updated review of pathogenesis, diagnosis, and treatment options.

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.

Clinical Outcomes in Sebaceous Carcinoma: A Retrospective Two-Center Cohort Study.

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.

Base-Excision Repair Mutational Signature in Two Sebaceous Carcinomas of the Eyelid.

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.

Intraepithelial growth pattern for eyelid sebaceous carcinoma: a cohort of 214 patients from a single institution.

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.

Malignant lesions of the caruncle.

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.

HPV-associated Vulvar Intraepithelial Carcinoma With Sebaceous Differentiation: Report of 2 Cases.

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.

Sebaceous Carcinoma of the Face Treated With Mohs Micrographic Surgery.

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.

Clinical Features and Prognosis of Young and Middle-Aged Adults With Skin Sebaceous Adenocarcinoma.

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.

Sebaceous Adenocarcinoma in Parotid Gland of a 65-Year-Old.

Sebaceous adenocarcinoma of the parotid gland is a rare, malignant epithelial neoplasm with focal areas of sebaceous differentiation. A literature search revealed only 34 cases as of December 2020. Our case brings this total to 35. It is characterized as a partially encapsulated neoplasm with predominant areas of basaloid or squamous cells, and variable degrees of sebaceous differentiation. The sebocytes display an immunohistochemical staining pattern of EMA (cytoplasmic vesicles), CD15, lactoferrin, GCDFP-2, and androgen receptor positivity in the sebocytes. Bimodal peaks occur in the third and seventh decades of life. We present a case of sebaceous adenocarcinoma in a 65-year-old male who initially presented in the emergency department with hypertensive urgency and vertigo. MRI and CT scans showed a heterogeneous mass with a solid component and cystic areas, including calcifications that measured approximately 2.7 x 2.1 x 4.1 cm, predominantly in the deep part of the left parotid gland and extending upward to the adjacent sternocleidomastoid muscle and possibly infiltrating or abutting the muscle. Further questioning of the patient revealed a seven month history of a painless, slow-growing mass and increased sensation of fullness on the left side of his neck. Patient underwent a left total parotidectomy with flap reconstruction and left neck dissection, revealing a 6.0 x 4.4 x 2.2 cm left parotid gland with a 2.4 x 2.2 x 1.6 cm, well-circumscribed, multiloculated cystic mass that released red-brown serous fluid and thick yellow material and appeared to abut multiple resection margins. Microscopic examination showed nests of basaloid cells at the periphery and areas of distinct sebaceous differentiation, separated by bands of extensive hyalinization. The tumor also displayed an average of 2 mitotic figures per 10 high power fields, and less nuclear atypia and less invasiveness into the surrounding glandular tissue than what has been described in sebaceous adenocarcinomas. This is an unusual case because of the rarity of the tumor as well as the lack of nuclear atypia and invasiveness compared to what is described of sebaceous adenocarcinoma in the literature.

Sebaceous adenoma occurring within an intracranial dermoid cyst.

Among intracranial cystic lesions, dermoid cysts and epidermoid cysts are relatively common benign tumors. In a small number of these tumors, it is known that squamous cell carcinomas arise in the lining epithelium of the cysts. Among tumors derived from the appendage, only one case of hidradenoma within a dermoid cyst and no cases of sebaceous tumor have been reported previously. In the present case, a protruding lesion was present in the cystic wall, and it was composed of two cell types: sebaceous cells (sebocytes) and basaloid/germinated cells, being characteristic of this tumor. It is essential to distinguish it from other sebaceous lesions such as hyperplasia, sebaceoma, sebaceous carcinoma, and basal cell carcinoma with sebaceous differentiation derived from the epidermis. The critical distinguishing points in making a differential diagnosis among these lesions are the ratio of the two cell types and the presence or absence of other components such as hair sacs, invasion or cellular atypia. Immunohistochemical examination revealed that the tumor cells were positive for the epithelial markers, such as cytokeratin (CK)14, p63, p40, high-molecular CK, and adipophilin; these findings are peculiar to sebaceous adenoma. Although there have been several similar case reports of sebaceous tumors associated with dermmoid cysts in the ovaries, most of the intracranial lesions were squamous cell carcinomas that developed within the cysts, and there has been no precedent showing an association with a sebaceous tumor. The present report describes the first case of sebaceous adenoma that occurred in an intracranial dermoid cyst.

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 73.5 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.