eMedicine Specialties > Dermatology > Malignant Neoplasms

Sebaceous Carcinoma

James M Spencer, MD, Professor of Clinical Dermatology, Mount Sinai School of Medicine, New York; Private Practice, Spencer Dermatology, St Petersburg, Florida
Amy Lynn Basile, DO, MPH, Sun Coast Hospital/Largo Medical Center, Largo, Florida

Updated: Feb 19, 2009

Introduction

Background

Sebaceous gland carcinoma is an aggressive, uncommon, cutaneous tumor first well-described by Allaire in 1891.¹ This tumor is thought to arise from sebaceous glands in the skin and, thus, may arise anywhere on the body where these glands exist, including the genitalia.^2,3,4 Approximately 75% of these tumors arise in the periocular region, an area rich in a variety of types of sebaceous glands.^5,6 This tumor exhibits an aggressive clinical course, with a significant tendency for both local recurrence and distant metastasis.

Diagnosis and therapy tend to be delayed because sebaceous carcinoma is frequently mistaken for more common benign entities, further complicating treatment of this aggressive malignancy.^7,8,9,10 In addition to its varied clinical appearance, a varied histologic appearance may occur, and delayed diagnosis or misdiagnosis following a biopsy is not uncommon.^7,8,9

When arising in the periocular region, the clinical presentation is often variable, and sebaceous gland carcinoma is often not initially suspected. Instead, patients may receive multiple courses of incision and drainage for chalazion before a definitive biopsy is performed.^7,11

Most sebaceous gland carcinomas have no obvious etiology. Only a few are associated with Muir-Torre syndrome. Although sebaceous adenoma and epithelioma are more specific markers for Muir-Torre syndrome, an evaluation for this syndrome is advisable once sebaceous gland carcinoma is diagnosed.¹² In approximately 40% of cases, patients with Muir-Torre syndrome develop some type of sebaceous tumor before or concurrent with visceral malignancy.¹³

Pathophysiology

Modern tumor classification schemes name tumors for the type of normal adult tissue toward which the tumor appears to be differentiating. The cell of origin is often not known. Sebaceous gland carcinoma clearly resembles normal sebaceous glands.¹⁴ One may reasonably speculate that sebaceous gland carcinoma arises from mature sebaceous glands. Histologic studies have suggested that periocular sebaceous gland carcinomas arise from the sebaceous glands in this region. The following 5 types of sebaceous glands are seen in the periocular region^5,6 :

• Meibomian glands of the tarsal plate
• Glands of Zeis of the cilia
• Sebaceous glands of the eyebrows
• Glands of the caruncle
• Glands of the fine hair follicles of the eyelid surface

Frequency

United States

Sebaceous gland carcinoma is a rare tumor. Approximately 75% of sebaceous gland carcinomas occur in the periocular region.⁵ In this region, sebaceous gland carcinoma represents 1-5.5% of eyelid malignancies, fourth after basal cell carcinoma, squamous cell carcinoma, and melanoma.^15,23,24

International

Sebaceous gland carcinoma seems to occur with greater frequency relative to other skin cancers in Asian populations. In a large retrospective series from China, sebaceous gland carcinoma was the second most common periocular tumor after basal cell carcinoma, reported to represent 33% of eyelid malignancies.²⁴

Mortality/Morbidity

Sebaceous gland carcinoma is an aggressive tumor, with a tendency for both local recurrence and distant metastasis.

• Reported local recurrence rates range from 9-36%, with larger series reporting recurrence rates in the 30% range. Local recurrence tends to occur within 5 years.^5,9
• The rate of metastasis in extraocular and ocular sebaceous carcinoma is thought to be similar, occurring in 14-25% of cases, first to the draining lymph nodes and then to distant sites.^7,15,25 Sites of distant metastasis include the liver, lungs, bones, and brain.^7,15,26 Metastasis has been reported to occur as late as 5 years after the initial diagnosis, lending support to the continual surveillance of patients with sebaceous carcinoma.²⁶

Sex

Women tend to be affected somewhat more often than men, with 57-77% of patients being women in several large series.^{7,14,15,27,28,29}

Age

Most patients present in their sixth or seventh decade of life, although the range is from early childhood through the nineties.^14,30 The youngest reported case arose in a 3-year-old child.³¹

Clinical

History

• The presentation of sebaceous gland carcinoma is often nonspecific, and a noncancerous condition of the periocular area may be mistakenly assumed. A biopsy-confirmed diagnosis is typically delayed for months, and even years, after the patient becomes aware of the condition.^9,28
• Most often, a painless nodule develops on the eyelid, and the patient receives treatment for the far more common benign chalazion.^5,7,11

Physical

Sebaceous gland carcinoma has a varied clinical presentation that often results in delayed diagnosis.

• Tumors of the upper lid are 2-3 times more common than lesions of the lower lid.^5,15,27,29
• The most common presentation is a firm, slowly enlarging nodule of the upper eyelid, often mistaken for a chalazion.^5,7,11 Patients are not uncommonly treated for many months for recurrent chalazia before a biopsy is performed.

In a variety of series, the delay in diagnosis following presentation ranges from 1-5 years.^9,28

• Loss of cilia is a clinical clue that the lesion is malignant.²⁹
• One study reported 7 of 31 patients presented with a characteristic “tigroid” pattern of the conjunctiva, described as yellow streaks (lipid material from the meibomian glands) within an area of papillary hypertrophy.⁹
• Clinical presentation can mimic keratoconjunctivitis, aroconjunctivitis,^7,11 squamous cell carcinoma, basal cell carcinoma, cutaneous horn,³² sarcoidosis, ocular pemphigoid, and a variety of benign and malignant ocular tumors.^5,9
• Extraocular sebaceous gland carcinoma represents 25% of reported tumors.³³
• The head and the neck are where most extraocular sebaceous gland carcinomas occur, with the parotid gland alone representing 30% of cases.³³
• Rare reports describe tumors arising in virtually every area of the body. Unusual anatomical locations reported in association with sebaceous carcinoma include the genitalia,^3,5 the parotid gland,³⁴ the ear canal,³⁵ the breast,^36,37 and the intraoral cavity²
• The clinical presentation is nonspecific and is usually described as a nodule that is pink to yellow-red.⁵

Causes

The cause of sebaceous gland carcinoma remains unclear. No association with ultraviolet radiation has been documented, but a history of ionizing radiation has been reported. Reports of prior radiation therapy for a variety of benign and malignant conditions include radiation for cavernous hemangioma, barber's itch, and retinoblastoma.^30,38,39

• In one series of 20 patients with sebaceous gland carcinoma, 8 patients had a history of diuretic use, and a possible association was suggested.⁸
• Sebaceous gland carcinoma seems to be more common in Asian populations than in other populations, and involvement of human papillomavirus (HPV) has been suggested as a possible etiologic factor in these populations.
  • One paper from Japan reported the presence of HPV DNA in some sebaceous gland carcinomas, as well as an overexpression of TP53.⁴⁰  
  • A study from the United States failed to detect HPV, but it did find overexpression of TP53.⁴¹
• Experimental evidence in animals has implicated chalazia as a possible factor in the development of sebaceous gland carcinoma.
  • Chalazia are caused by inflammation of the meibomian glands or glands of Zeis that results in the formation of a hard, usually painless, nodule in the eyelid.
  • Histologically, chalazia contain granulomatous inflammation, areas of caseation necrosis, and an unsaturated 8-carbon fatty acid called oleic acid. Animal studies have suggested possible carcinogenicity with exposure to oleic acid, and prolonged exposure to this molecule within chalazia may induce dysplastic growth in glandular structures.
• Genetic factors clearly play a role, because sebaceous gland carcinomas are part of the genodermatosis Muir-Torre syndrome.
  • Muir-Torre syndrome is a rare autosomal dominant condition with variable penetrance characterized by skin manifestations, including benign and malignant sebaceous neoplasms, keratoacanthomas, and internal manifestations (eg, colonic polyps, low-grade visceral malignancies).¹²
  • A diagnosis of Muir-Torre syndrome requires the presence of both an internal malignancy and a sebaceous neoplasm.¹² The sebaceous neoplasms encompass a spectrum from well-differentiated sebaceous hyperplasia through undifferentiated sebaceous gland carcinoma.¹²
  • In one literature review of 120 patients with Muir-Torre syndrome, 29 had sebaceous gland carcinoma, 50% of which were ocular.¹³
  • Sebaceous neoplasms developed before or concurrent with visceral malignancies in 41% of patients in one series.¹³
  • Colorectal carcinoma is the most common internal malignancy in Muir-Torre syndrome, followed by genitourinary malignancy.¹³
  • A variety of internal malignancies, including head and neck, small bowel, and hematologic, occur less frequently in Muir-Torre syndrome.
  • Sebaceous gland carcinoma is clearly part of Muir-Torre syndrome. However, the percentage of patients with sebaceous gland carcinoma who will develop Muir-Torre syndrome is not clear.¹²
  • All patients with sebaceous gland carcinoma should be evaluated for Muir-Torre syndrome.

Differential Diagnoses

Other Problems to Be Considered

Chalazion
Keratoconjunctivitis
Blepharoconjunctivitis
Conjunctival carcinoma in situ
Leukoplakia
Ocular pemphigoid
Granulomatous inflammation from syphilis or tuberculosis
Central retinal artery occlusion and proptosis
Lacrimal gland tumors
Exophthalmos
Benign adnexal tumors

Workup

Laboratory Studies

• Baseline studies include liver function tests, electrolyte levels, and a complete blood cell count to rule out metastatic disease and to establish a baseline for future care. Normal results of these tests also help to rule out any tumors associated with Muir-Torre syndrome.
• More detailed studies can be directed by these findings.

Imaging Studies

• Chest radiography may be performed to rule out metastatic disease and to establish a baseline for future care.

Other Tests

• A systemic evaluation includes a complete medical and family history and a physical examination, including a detailed ophthalmologic examination, palpation of the lymph nodes, a thorough skin examination, and a review of systems.
• Evaluation for Muir-Torre syndrome includes a preliminary rectal examination, colonoscopy or barium enema, and a first-morning urine for cytologic analysis.
  • Colorectal carcinoma is the most common visceral malignancy in Muir-Torre syndrome.¹³ Most of these malignancies occur proximal to the splenic flexure, and, thus, digital examination and flexible sigmoidoscopy would be inadequate to aid in the diagnosis.
  • The urine cytologic analysis is used to screen for genitourinary malignancy.

Procedures

• Successful diagnosis results from suspecting this rare tumor in the first place and performing an adequate biopsy.
• A full-thickness eyelid biopsy is generally recommended in cases in which a papular or nodular primary tumor is evident.^10,42
• Some authors have recommended fine-needle aspiration for primary and metastatic sebaceous gland carcinoma,^43,44 but a full-thickness surgical biopsy is mandatory if the results are negative or equivocal.
• Approximately 50% of patients have clinically inapparent extension of tumor cells in the surrounding epidermis, termed pagetoid spread. This may extend considerable distances beyond the main body of the tumor. Conjunctival map biopsies are recommended to delineate the presence and extent of pagetoid spread.⁴⁵
• Parotidectomy has also been reported in cases of sebaceous carcinoma with regional lymphadenopathy or metastasis.⁹ Given the potential for metastasis to the parotid gland, further evaluation is warranted, particularly with an upper eyelid sebaceous carcinoma.^6,27,33

Histologic Findings

Sebaceous gland carcinoma demonstrates disordered invasion of the dermis by lobules of poorly defined sebaceous cells or basaloid/squamoid cells.⁴⁶ Sebocytes tend to have multivacuolated clear cytoplasm, causing the nucleus to be scalloped from the lipid invasion.¹⁴ In many cases, moderate-to-severe atypia can be found, as well as a high nuclear/cytoplasm ratio and a perinuclear halo, identified in all 30 cases presented by Izumi et al.¹⁴ In some cases, well-developed sebocytes can be identified; in a smaller number of cases, sebaceous duct differentiation can be seen.¹⁴ Sebaceous carcinoma can be stained positively with oil red-O or Sudan black, which are specific for cytoplasmic fat, but epithelial membrane antigen (EMA) immunoperoxidase staining may be a better supplemental stain for confirming sebaceous differentiation.⁴⁷

Sebaceous gland carcinoma may also exhibit clinically inapparent extension beyond the obvious tumor within the adjacent epithelia. Cells seen in the adjacent epithelia, often appearing to be separate from the main tumor, are known as pagetoid spread. This typically occurs within the conjunctivae, but it can also occur in the adjacent skin or the cornea. This phenomenon is seen in approximately 40-80% of reported series.¹⁰ The significance of these intraepithelial cells is unclear, with some authors reporting a worse prognosis when present¹⁵ and others reporting no significant difference in outcome when present. Given the possibility that these cells represent tumor infiltration rather than premalignant or reactive cells, a conjunctival map biopsy to delineate the presence and the extent of pagetoid spread seems warranted.⁴⁵

Treatment

Medical Care

Sebaceous gland carcinoma is an aggressive tumor with a tendency for both local recurrence and metastasis. Delay in diagnosis may contribute to the poor outcome in this tumor; therefore, a high degree of suspicion when eyelid lesions occur and a willingness to perform a biopsy will most likely contribute to a better prognosis for patients with this tumor. Radiation therapy has traditionally been considered palliative but not curative.

• In a small series of 6 patients, all 6 experienced a relapse 2 months to 2 years following radiation therapy, but they remained tumor-free following subsequent surgery.⁴⁸
• Rao et al reported a mortality rate of 78% in patients treated primarily with radiation therapy, in contrast to a rate of 7% for those treated with wide excision¹⁵ ; however, one case report describes 2 patients who refused surgery who were successfully treated with radiation therapy⁴⁹ and another case series describes 2 patients who underwent radiation therapy as well, with no recurrence after 27 and 36 months, respectively.²⁷
• Drawing conclusions from only a few cases is premature, but the possibility exists that advancements in radiation technology and technique may make this a viable therapeutic option in the future.
• While the significance of pagetoid spread is debated, most authors agree treatment of this epithelioid spread is warranted. It has been suggested, but not studied, that topical chemotherapy to the involved conjunctivae following surgical excision of the invasive tumor may be beneficial.^27,29

Surgical Care

Sebaceous gland carcinoma remains a dangerous tumor and produces significant morbidity and mortality. Heightened awareness by the clinician and early biopsy may impact management of this rare tumor. Therapeutically, cryosurgery and surgical excision have been used for sebaceous carcinoma.²⁹

• Cryosurgery has been useful for a variety of cutaneous tumors and holds the theoretic advantage of treating large areas of conjunctivae if pagetoid spread is present. Long-term studies evaluating the use of cryosurgery for sebaceous gland carcinoma with pagetoid spread need to be performed.
• Surgery has been and remains the primary treatment modality for sebaceous gland carcinoma. When orbital involvement is documented, therapy has traditionally been orbital exenteration.⁴² Without orbital involvement, surgical therapy typically involves excision of the visible tumor plus 5-6 mm of healthy-appearing tissue in all directions, followed by either frozen section or permanent section for histologic analysis.⁵⁰ This approach has not been completely satisfying, because local recurrence occurs in approximately one third of patients.
• The use of the fresh tissue Mohs technique has been successful in a number of case reports; however, many of these reports are limited to 1-3 cases each for a total of approximately 75 cases in the literature, and the findings cannot be considered definitive. Nonetheless, a retrospective review of 49 cases of sebaceous carcinoma reveals a local recurrence rate of 12% (6/49) and a metastatic rate of 8%.⁵¹
• This author has treated 18 patients with periocular sebaceous gland carcinoma using the fresh tissue Mohs technique, with an average follow-up period of 37 months. Two of these 18 patients had lesions recur, for a recurrence rate of 11.1%, and one of these patients also developed metastatic disease to the parotid lymph nodes, for a metastatic rate of 5.6%.⁵⁰ This is a significant improvement over the local recurrence rate of 32% reported following conventional surgery.⁵ Given our current understanding of the treatment of sebaceous gland carcinoma, excision using the Mohs technique may become the treatment of choice.
• The treatment of tumors with pagetoid spread remains controversial. Some authorities have suggested that complete excision of involved epithelia is necessary, while others have suggested only frank invasive tumor needs to be treated, after which only careful clinical observation of the involved epithelia is warranted. Given the aggressive nature of this tumor, treating pagetoid spread as direct tumor extension and continuing surgical excision until all margins are clear, including clear of pagetoid spread, is wise.⁵² In this author's series of 18 patients, 9 had pagetoid spread, and surgery was continued until the conjunctivae was clear because pagetoid spread can be seen on frozen sections.⁵⁰ Future larger series are needed to better delineate the true significance of pagetoid spread.

Consultations

Referral to an internist and gastroenterologist is warranted in patients diagnosed with sebaceous carcinoma in order to evaluate for the presence of internal (internist) and bowel (gastroenterologist) lesions associated with Muir-Torre syndrome.

Follow-up

Prognosis

• Sebaceous gland carcinoma is an aggressive tumor, with a tendency for both local recurrence and distant metastasis.
• Reported clinicopathological features associated with a poor prognosis include orbital invasion, upper and lower eyelid involvement, poor differentiation,⁵³ lacrimal gland involvement,⁵³ tumor diameter greater than 10 mm,⁵⁴ pagetoid spread, and symptom duration greater than 6 months.¹⁵
• Reported local recurrence rates range from 9-36%, with larger series reporting recurrence rates in the range of 30%.⁵ Local recurrence tends to occur within 5 years.
• Metastasis occurs in 14-25% of patients.¹⁵ It first spreads to the draining lymph nodes and then to distant sites. Sites of distant metastasis include the liver, lungs, bones, and brain.²⁶
• The 5-year mortality rate for patients with metastatic disease is reportedly 50-67%.⁵⁵

Miscellaneous

Medicolegal Pitfalls

• Misdiagnosis as a more common benign entity may cause delay in appropriate treatment. However, delayed diagnosis or misdiagnosis is not uncommon with this clinically subtle tumor.
• Failure to evaluate patients with a diagnosis of sebaceous carcinoma for Muir-Torre syndrome is a pitfall.

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Keywords

sebaceous carcinoma, sebaceous gland carcinoma, meibomian gland carcinoma, sebaceous cell carcinoma

Contributor Information and Disclosures

Author

James M Spencer, MD, Professor of Clinical Dermatology, Mount Sinai School of Medicine, New York; Private Practice, Spencer Dermatology, St Petersburg, Florida
James M Spencer, MD is a member of the following medical societies: American Academy of Cosmetic Surgery, American Academy of Dermatology, American College of Mohs Micrographic Surgery and Cutaneous Oncology, American Dermatological Association, American Medical Association, American Society for Dermatologic Surgery, American Society for Laser Medicine and Surgery, and International Society for Dermatologic Surgery
Disclosure: Graceway Pharmaceutical Honoraria Speaking and teaching; Sanofi Aventis Honoraria Consulting; Medicis Grant/research funds Other

Coauthor(s)

Amy Lynn Basile, DO, MPH, Sun Coast Hospital/Largo Medical Center, Largo, Florida
Amy Lynn Basile, DO, MPH is a member of the following medical societies: American Medical Association, American Osteopathic Association, and American Osteopathic College of Dermatology
Disclosure: Nothing to disclose.

Medical Editor

Kelly M Cordoro, MD, Fellow and Clinical Instructor, Department of Pediatric Dermatology, University of California at San Francisco; Assistant Professor (On Educational Leave), Assistant Program Director for Resident Medical Education, Department of Dermatology, University of Virginia School of Medicine
Kelly M Cordoro, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Association of Professors of Dermatology, Dermatology Foundation, Medical Society of Virginia, National Psoriasis Foundation, Society for Pediatric Dermatology, and Women's Dermatologic Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University School of Medicine; Consulting Staff, Mountain View Dermatology, PA
Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

John G Albertini, MD, Consulting Staff, Dermatologic Surgery, The Skin Surgery Center
John G Albertini, MD is a member of the following medical societies: American Academy of Dermatology and American College of Mohs Micrographic Surgery and Cutaneous Oncology
Disclosure: Nothing to disclose.

CME Editor

Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University
Catherine Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

The authors and editors of eMedicine gratefully acknowledge the contributions of previous Chief Editor, William D. James, MD, to the development and writing of this article.

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