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.

Nasolacrimal duct obstruction secondary to lacrimal sac involvement by sebaceous carcinoma.

Sebaceous carcinoma (SC) is the third most common eyelid malignancy in Australia, and is potentially fatal. It usually presents as a nodule or diffuse eyelid thickening, and is commonly misdiagnosed. We describe a case of SC with lacrimal sac involvement, presenting with clinical features of nasolacrimal duct obstruction. At the time of endoscopic dacryocystorhinostomy (DCR), nasal endoscopy revealed a polypoid mass of the opened lacrimal sac. Biopsy of the mass showed poorly differentiated SC. The lacrimal drainage apparatus was later excised via a combined external and endoscopic approach. Conjunctival map biopsies showed extensive intraepithelial disease, which was treated with topical mitomycin C. At three-month follow-up, there was no evidence of residual disease on nasal endoscopy or repeat conjunctival biopsy.

Sebaceous carcinoma in association with actinic keratosis: A report of two cases with an immunohistochemical study.

We report two cases of sebaceous carcinoma associated with actinic keratosis (AK) with an immunohistochemical study, which suggests the possibility that sebaceous carcinoma really does develop within AK. Case 1 had sebaceous carcinoma arising within the atrophic type AK and case 2 had sebaceous carcinoma associated with bowenoid AK in the periphery and some parts of the overlying epidermis of the lesion.

Extraocular sebaceous carcinoma: a report of 2 cases.

Sebaceous carcinoma is a rare, aggressive adnexal tumor of unknown etiology; 75% of these tumors arise in the periocular region while 25% arise at extraocular sites. This cutaneous tumor is a diagnostic sign of Muir-Torre syndrome, a disorder associated with visceral malignancies and gene abnormalities. Patients with sebaceous carcinoma should therefore be carefully evaluated; a detailed personal and family history of cancer, a thorough physical examination, additional tests where appropriate, and close monitoring will all be required. We report 2 cases of extraocular sebaceous carcinoma and review the literature, focusing on the association between sebaceous carcinoma and Muir-Torre syndrome.

Sebaceous adenoma arising within an ovarian mature cystic teratoma in Muir-Torre syndrome.

This is the first reported case of a sebaceous adenoma arising within an ovarian mature cystic teratoma in a patient with Muir-Torre syndrome. The pathologic findings and a literature review are presented, including the importance and possible benefits of an early diagnosis of Muir-Torre syndrome. It is proposed that the presence of a sebaceous adenoma in an ovarian cystic teratoma may serve as a useful trigger to consider further history and investigations, with the goal of identifying an important genetic cancer predisposition syndrome.

Sebaceous neoplasia and the Muir-Torre syndrome: important connections with clinical implications.

Sebaceous neoplasia comprises a spectrum ranging from benign to malignant. Proper histological identification is important for treatment, prognosis and potential association with the Muir-Torre syndrome (MTS). Our increased understanding of the significance and pathogenesis of these tumours has led to improved risk stratification, screening recommendations, and treatment of patients with an initial presentation of a sebaceous tumour. This review focuses on the diagnostic and histological features of sebaceous lesions, the MTS, and recent insights into the molecular pathogenesis of sebaceous tumours.

Epidermal growth factor receptor (EGFR) expression in periocular and extraocular sebaceous carcinoma.

Sebaceous carcinoma has a predominant periocular origin but can also be extraocular. These two groups have distinct clinical courses. Insight into the molecular determinants of tumorigenesis and metastasis is limited. There is no effective treatment for metastatic sebaceous carcinoma. Epidermal growth factor receptor (EGFR) is implicated in tumorigenesis and can be a therapeutic target in certain settings. We evaluated EGFR levels by immunohistochemistry (IHC), comparing its expression between periocular and extraocular tumors and assessed EGFR mutation status. IHC was performed in 36 cases: 19 periocular and 17 extraocular (10 associated with Muir-Torre syndrome-MTS). EGFR IHC was scored for percentage of positive cells (< 5%, 5-25%, 26-50%, > 50%) and intensity (+1 = low , +2 = moderate , +3 = high ). Extraocular carcinomas showed markedly increased levels of EGFR when compared to periocular carcinoma cases, both in terms of distribution (88% were > 25% of tumor cells vs. 16%) and intensity (77% were 2+ or 3+ vs. 21%) (p < 0.001). Among extraocular cases, there was significantly lower EGFR expression in MTS-related cases (p < 0.05). No EGFR mutations were identified. Our results underscore the divergent mechanisms underlying the tumorigenesis of periocular and extraocular sebaceous carcinoma and suggest an association between aggressive behavior and increased EGFR expression in extraocular sebaceous carcinoma.

Sebaceous carcinoma of the breast.

Sebaceous carcinoma (SC) of the breast is a rare malignant tumor and only nine cases, including the present one, have been reported in the English-language literature. The present report describes a case of mammary SC in a 50-year-old Japanese woman. The tumor was gray-white on cut surface and separate from the skin and the nipple. Microscopically, lobules encircled by a fibrous envelope and cords or small cell nests in the stroma were noted. These two types of structures were composed of dark cells and clear foamy cells. The dark cells had large nuclei and amphophilic cytoplasm. The clear foamy cells had numerous lipid vacuoles, confirmed on immunostaining with anti-adipophilin antibody and electron microscopy. In the lobules the gradual transitions from basal dark cells to central clear foamy cells and comedo-like necrosis were observed. The tumor cells were positive on immunohistochemistry for cytokeratins (CAM5.2, AE1/AE3), Her2/neu and androgen receptor but negative for estrogen and progesterone receptors. This is the first case of an androgen receptor-positive mammary SC to be reported, and therefore contributes to the understanding of the clinicopathological features of SC of the breast.

Tumores sebáceos: seguimiento clínico y presencia de neoplasias en una serie de 12 pacientes / Clinical follow-up and presence of visceral tumors in 12 patients with sebaceous gland tumors

Introducción. Los tumores sebáceos son un grupo infrecuente de neoplasias. En algunos casos se han relacionado con neoplasias viscerales en pacientes con el síndrome de Muir-Torre; una variante clínica del síndrome de cáncer de colon hereditario no polipósico. El objetivo de este trabajo es revisar el diagnóstico y el seguimiento de una serie de pacientes con tumores sebáceos para comprobar cuántos de ellos cumplían criterios de síndrome de Muir-Torre. Pacientes y métodos. Se realizó una búsqueda en la base de datos del Servicio de Dermatología del Consorcio Hospital General Universitario de Valencia entre 1990 y 2005, buscando pacientes con tumores sebáceos. Se revisaron las biopsias para confirmar el diagnóstico. También buscamos datos en las historias clínicas que sugiriesen un diagnóstico de síndrome de Muir-Torre, cuando las historias estaban incompletas nos pusimos en contacto por teléfono con los pacientes. Resultados. Encontramos 20 pacientes diagnosticados de tumores sebáceos, pero después de revisar la biopsia sólo confirmamos este diagnóstico en 12 pacientes. Dos pacientes pertenecían a una familia con antecedentes de neoplasias viscerales, que cumplía los criterios clínicos de síndrome de cáncer de colon hereditario no polipósico. No hubo un seguimiento uniforme de los pacientes ni se realizaron las mismas pruebas en todos ellos. Conclusiones. Es fundamental descartar la presencia de un síndrome de Muir-Torre en pacientes con tumores sebáceos. El uso de nuevas técnicas como la detección de la inestabilidad de micro satélites o la inmunohistoquímica pueden ayudar a detectar a las familias que tienen un mayor riesgo de padecer el síndrome de Muir-Torre (AU)

Background. Sebaceous gland tumors are a rare type of neoplasm. In some cases they have been associated with visceral tumors in patients with Muir-Torre syndrome, a hereditary form of non polyposis colorectal cancer. The aim of this study was to review the diagnosis and follow-up of a series of patients with sebaceous gland tumors to assess how many met the criteria for Muir-Torre syndrome. Patients and methods. A search was performed of records from 1990 to 2005 in the database of the Department of Dermatology of the Consorcio Hospital General Universitario de Valencia in Valencia, Spain, to identify patients with sebaceous gland tumors. The biopsy material was reviewed to confirm the diagnosis. We also searched the patient histories for information suggestive of a diagnosis of Muir-Torre syndrome; when the histories were incomplete, we contacted the patients by telephone. Results. We identified 20 patients diagnosed with sebaceous gland tumors, but after reviewing the biopsy material diagnosis was only confirmed in 12. Two patients belonged to a family with a history of visceral tumors that met the clinical criteria for hereditary nonpolyposis colorectal cancer syndrome. Follow-up was not uniform in all patients and not all underwent the same tests. Conclusions. It is essential to rule out the presence of Muir-Torre syndrome in patients with sebaceous gland tumors. The use of new techniques such as immunohistochemistry or detection of microsatellite instability may help to identify families at increased risk of Muir-Torre syndrome (AU)

Morpheaform extra-ocular sebaceous carcinoma.

BACKGROUND: Sebaceous carcinoma is an unusual, aggressive, malignant tumor derived from the epithelium of sebaceous glands. It may arise in ocular or extra-ocular sites and is often evident as an ulcerated or non-ulcerated cystic nodule measuring up to 8 cm in diameter. A significant number of extra-ocular sebaceous carcinomas have been associated with metastases and high mortality rate. METHODS AND RESULTS: We reviewed the literature in the context of our report of a 68-year-old woman who had a morpheaform plaque of the upper lip of 15 years duration, extending into the left naso-genal groove, which histologically also showed marked stromal fibrosis. Three years after excision, there were no signs of recurrence or metastases. CONCLUSIONS: This patient is unusual in clinical and histologic pattern, as a morpheaform appearance has only been described previously in only one sebaceous carcinoma. In addition, no metastatic disease 15 years after tumor onset is a fortunate and remarkable feature.

Sebaceous carcinoma, basal cell carcinoma, trichoadenoma, trichoblastoma, and syringocystadenoma papilliferum arising within a nevus sebaceus.

BACKGROUND: Nevus sebaceus has a well-documented potential to develop a wide variety of neoplasms of both epidermal and adnexal origins. It is highly unusual for more than three tumors to arise simultaneously within a single nevus sebaceus. Sebaceous carcinoma arising within a nevus sebaceus is a rare occurrence. OBJECTIVE: The objective was to report the case of a patient with a nevus sebaceus that simultaneously developed five distinct neoplasms of epidermal and various adnexal origins and to report the fourth case of sebaceous carcinoma arising within a nevus sebaceus. METHODS: A 45-year-old woman presented with a nevus sebaceus that contained five separate neoplasms, including sebaceous carcinoma, basal cell carcinoma, trichoadenoma, trichoblastoma, and syringocystadenoma papilliferum. RESULTS: Complete excision of the nevus sebaceus and the five tumors was performed. Systemic work-up showed no evidence of metastatic disease or association with Muir-Torre syndrome. CONCLUSION: This case report highlights the diverse neoplastic potential of nevus sebaceus and demonstrates the capacity of this hamartoma to develop aggressive tumors, such as sebaceous carcinoma. Prophylactic excision or at least close clinical surveillance for sudden development of new growths is warranted in all cases of nevus sebaceus.

Carcinoma sebáceo nasal. A propósito de un caso / Nasal sebaceus carcinoma. About a case

Se presenta un caso clínico de un carcinoma sebáceo extra-ocular, en un varón de 71 años de edad con una tumoración en ala nasal derecha (AU)

Multiple sebaceous adenomas and extraocular sebaceous carcinoma in a patient with multiple sclerosis: case report and review of literature.

BACKGROUND: Sebaceous carcinomas are relatively rare cutaneous tumors; there are fewer than 600 cases reported. They most commonly arise within the meibomian gland of the eyelid; fewer than 150 of the reported cases were extraocular. These tumors have a high incidence of local recurrence and regional metastasis. The relationship of sebaceous tumors and visceral malignancy is well established in the literature. OBJECTIVE: We describe a 44-year-old white female with chronic progressive multiple sclerosis who developed multiple scalp sebaceous adenomas and a solitary sebaceous carcinoma. CONCLUSION: Extraocular sebaceous carcinomas are rare tumors with high incidence of local recurrence and regional metastasis. Surgery with wide surgical margins is the standard treatment. We report the first case of multiple sebaceous tumors in a patient with multiple sclerosis. The presence of sebaceous tumors warrants a search for an internal malignancy. Literature on sebaceous tumors and their relationship with visceral malignancies and immunologic disorders is discussed. Literature on sebaceous carcinoma with special attention to extraocular sebaceous carcinoma is also discussed.