REVIEW ARTICLE INCENTIVE PROGRAM WINNER

Sebaceous Carcinoma: Review of the Literature Rachel L. Kyllo, MD,* Kimberly L. Brady, MD,† and Eva A. Hurst, MD†

BACKGROUND Sebaceous carcinoma is an uncommon adnexal neoplasm with a documented capability for regional and distant metastasis. Traditionally, sebaceous carcinoma has been associated with high rates of recurrence after excision. OBJECTIVE To review the current literature on sebaceous carcinoma and detail its epidemiology, pathogenesis, clinical presentation, histopathology, diagnostic workup, treatment, and prognosis. MATERIALS AND METHODS

Literature review using PubMed search for articles related to sebaceous carcinoma.

RESULTS Sebaceous carcinoma typically presents as a painless pink or yellow nodule. Diagnosis requires histopathologic examination, and immunohistochemical analysis often assists in the differentiation of sebaceous carcinoma from other benign and malignant skin neoplasms. Sebaceous carcinoma should prompt a workup for Muir–Torre syndrome. Periorbital sebaceous carcinoma has an increased tendency for regional metastasis, although cancer-specific mortality rates are similar among all anatomic locations. CONCLUSION Surgery is the preferred treatment for local disease. Limited data suggest that Mohs micrographic surgery may provide superior clinical outcomes, but more research is needed regarding the long-term outcomes. Radiation and systemic chemotherapy are reserved for recurrent or metastatic disease. The authors have indicated no significant interest with commercial supporters.

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ebaceous carcinoma is a rare and potentially aggressive adnexal neoplasm. Although the first reported cases date to the late 19th century,1,2 controversy existed regarding classification until Straatsma1 published his detailed report that outlined histologic and clinical features in 1956. A variety of terms have been used in the literature to refer to sebaceous carcinoma, including sebaceous gland carcinoma,3–5 sebaceous cell carcinoma,6,7 and meibomian gland carcinoma.2,8–10 The recent literature has trended toward the use of the unified term sebaceous carcinoma.11–14 Because of its relative rarity and variable clinical presentation, sebaceous carcinoma is often misdiagnosed clinically, leading to delays in appropriate treatment. Complete surgical excision is the preferred treatment. This review presents the epidemiology, pathogenesis, clinical features,

histology, management, and prognosis of sebaceous carcinoma. We also provide a comprehensive literature review of the issues surrounding surgical management of this uncommon neoplasm.

Epidemiology Sebaceous carcinoma is an uncommon neoplasm. In 1 series reporting 4,000 cutaneous malignancies in a US population, sebaceous carcinoma represented only 0.7% of skin cancers.15 Another study that cataloged more than 42,000 skin cancers in Texas found the prevalence of sebaceous carcinoma relative to other cutaneous malignancies to be 0.05%.16 Sebaceous carcinoma of the eyelid represents approximately 1% of periorbital malignancies in the United States.17,18

*Washington University School of Medicine, St Louis, Missouri; †Department of Internal Medicine, Division of Dermatology, Washington University, St Louis, Missouri

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© 2014 by the American Society for Dermatologic Surgery, Inc. Published by Lippincott Williams & Wilkins ISSN: 1076-0512 Dermatol Surg 2015;41:1–15 DOI: 10.1097/DSS.0000000000000152

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SEBACEOUS CARCINOMA: REVIEW OF THE LITERATURE

Risk factors for sebaceous carcinoma reported in the historical literature include advanced age,3,19–21 female sex,19–22 and Asian race.20 Sebaceous carcinoma primarily affects elderly individuals, with most historical studies reporting an average age of onset in the 60s.3,19,21,22 More recent studies have demonstrated an increasing mean age of onset into the early 70s, possibly reflecting increases in overall life expectancy.23,24 Multiple case series have identified a female predominance among patients diagnosed with sebaceous carcinoma19–22,24; a review published in 1989 reported that women represented 63.2% of the 424 published cases to date.25 Recent literature has called into question this association,23,26,27 as a recent review of 1,349 US cases from the Surveillance, Epidemiology, and End Results (SEER) database found a slight predominance of men (54%).23 The often-quoted Asian predilection for sebaceous carcinoma has also been recently disputed. In 1982, Ni and colleagues published a retrospective review of malignant eye neoplasms in Shanghai and Boston. A larger proportion of eyelid neoplasms were found to be sebaceous carcinoma in Shanghai (32.7%) than in Boston (1.5%).20 Similar reports detailing higher relative proportions of sebaceous carcinoma in Indian and Nepalese populations have been published.28,29 Multiple review articles have since reported a higher “presumed incidence” of sebaceous carcinoma in Asian patients, although these studies reported relative proportions rather than actual incidences.11,12,14 The 2009 review of the SEER database by Dasgupta and colleagues23 found a significantly higher incidence of sebaceous carcinoma among whites (2.03 per million) versus Asian/Pacific Islanders (1.07 per million) in the United States (p = .0001). The most likely explanation for the divergent conclusions is the relatively low incidence of basal cell or squamous cell carcinomas in the Asian population, which leads to a larger relative proportion of sebaceous carcinomas in Asians without affecting absolute risk. Of note, sebaceous carcinoma occurs even less frequently in blacks than in Asians or whites (0.48 per million, p < .001).23

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Pathogenesis The pathogenesis of sebaceous carcinoma is poorly understood, and the cause of the majority of cases remains unknown.11,18 Notable associations with sebaceous carcinoma include Muir–Torre syndrome (MTS),30–37 a history of irradiation,4,38–40 immunosuppression,12,41–43 and familial retinoblastoma.24,44–48 Sebaceous carcinoma has rarely been reported to develop from nevus sebaceous.49–51 Muir–Torre syndrome is an autosomal dominant genodermatosis characterized by a sebaceous neoplasm (including sebaceous carcinoma) or keratoacanthoma associated with visceral malignancy.31 Muir–Torre syndrome is a variant of Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer. The affected genes include MLH1, MSH2, and MSH6; the protein products of these genes play important roles in DNA mismatch repair. Ineffective DNA mismatch repair results in microsatellite instability (MSI), which leads to the propagation of genetic defects within replicating cells and predisposition to tumor formation.52,53 Genotyping a sample of patient blood or saliva for MSI is often used to confirm the diagnosis of MTS.33 Interestingly, recent evidence has implicated a role for mutational inactivation of p53, a common tumor suppressor, in the pathogenesis of MTS-associated sebaceous neoplasms with intact mismatch repair54 and sporadic sebaceous carcinoma.55,56 Immunohistochemical analysis has also implicated a possible role of epidermal growth factor receptor and vascular endothelial growth factor receptor up-regulation in sebaceous carcinoma.57,58 It is likely that multiple molecular pathways contribute to the formation of sebaceous carcinoma; additional research is needed to determine whether molecularly targeted therapies have any use in treatment. Clinical Presentation Sebaceous carcinoma can occur in any skin containing sebaceous glands. Areas with a particularly high density of sebaceous glands (eyelids, face, scalp, and neck) expectedly have a higher incidence of sebaceous carcinoma. Within periorbital sebaceous carcinoma, the most common location is the upper eyelid.25 Wick and colleagues40 reported in 1985 that sebaceous

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KYLLO ET AL

carcinoma of the periorbital region represented 75% of all reported cases in the literature to date; this 3:1 ratio of periorbital to extraorbital tumors has subsequently been reported in numerous reviews on the subject.11–13 However, a recent epidemiologic study found the following distribution: 38.7% periorbital; 40.8% extraorbital skin of the head and neck; 19.9% other (trunk, extremities, or genitals); 0.6% unspecified or overlapping sites.23 This suggests that the relative proportion of extraorbital sebaceous carcinoma is much higher than previously estimated (approximately 60.7% of cases in the United States). The clinical differential diagnosis for sebaceous carcinoma includes a number of neoplastic and inflammatory conditions, which are summarized in Table 1. The typical presentation for sebaceous carcinoma is a painless pink or yellow nodule (Figure 1).11 However, clinical features can be quite varied (Figures 2 and 3), ranging from skin-colored to red papules, plaques, or nodules indistinguishable from other more common forms of skin cancer on clinical examination. Histologic analysis is ultimately required for diagnosis. Periorbital sebaceous carcinoma in particular is easily mistaken for benign conditions including chalazion, TABLE 1. Clinical Differential Diagnosis for Sebaceous Carcinoma Extraorbital Sebaceous Carcinoma

Periorbital Sebaceous Carcinoma

Benign sebaceous neoplasm

Chalazion

Basal cell carcinoma

Blepharitis

Figure 1. Sebaceous carcinoma presenting as a pink papule on the lower eyelid. Image reproduced with permission from Jeffrey Callan, MD, and VisualDx; Logical Images, Inc. Adaptations are themselves works protected by copyright. So in order to publish this adaptation, authorization must be obtained both from the owner of the copyright in the original work and from the owner of copyright in the translation or adaptation.

keratoconjunctivitis, and blepharoconjunctivitis, leading to delays in diagnosis and appropriate treatment.12,14,18,59–62 The most common presentation of periorbital sebaceous carcinoma is a painless subcutaneous nodule of the eyelid easily mistaken for a chalazion. However, a diffuse pseudoinflammatory pattern presenting with eyelid thickening mimicking keratoconjunctivitis or blepharoconjunctivitis (Figure 4) is also common. Rarely, periorbital sebaceous carcinoma may present as a pedunculated eyelid mass reminiscent of a cutaneous horn. These benign conditions are orders of magnitude more common than sebaceous carcinoma, and therefore a high index

Squamous cell carcinoma Conjunctivitis amelanotic melanoma Merkel cell carcinoma

Keratoconjunctivitis Basal cell carcinoma

Cutaneous lymphoma

Squamous cell carcinoma

Metastases

Benign sebaceous neoplasm

Nevus sebaceus

Amelanotic melanoma

Xanthoma

Merkel cell carcinoma

Sarcoidosis

Cutaneous lymphoma Metastases Nevus sebaceus Xanthelasma Ocular cicatricial pemphigoid

Figure 2. Sebaceous carcinoma presenting as a crusted pink and yellow nodular plaque. Photograph courtesy of Eva Hurst, MD.

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SEBACEOUS CARCINOMA: REVIEW OF THE LITERATURE

TABLE 2. Histologic Differential Diagnosis for Sebaceous Carcinoma Histologic Differential Diagnosis Sebaceous adenoma Sebaceoma Basal cell carcinoma 6 sebaceous differentiation Squamous cell carcinoma Clear cell eccrine hidradenocarcinoma Clear cell sarcoma Metastatic prostate carcinoma Metastatic renal cell carcinoma Melanoma Squamous cell carcinoma in situ Figure 3. Sebaceous carcinoma presenting as a well-circumscribed yellow and red nodule with central ulceration. Photograph courtesy of Sarah Arron, MD, PhD.

of suspicion is often required to make an early diagnosis of periorbital sebaceous carcinoma. Recurrent chalazion, eyelid thickening, lash loss, lid eversion, and ulceration of the eyelid should prompt eyelid biopsy for histologic diagnosis to rule out sebaceous carcinoma.18,60

Histopathology The histologic differential diagnosis for sebaceous carcinoma is summarized in Table 2. The classic histologic appearance of sebaceous carcinoma consists of unencapsulated, lobular, dermally based collections of sebaceous and undifferentiated cells (Figure 5).1,11,19,24 Lipid granules present in the cytoplasm of the cells result in their characteristic “frothy”

Figure 4. Periorbital sebaceous carcinoma presenting as chronic blepharitis with inflammation and thickening of the eyelid margin and diffuse eyelash loss. Photograph courtesy of Philip Custer, MD.

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Paget disease

appearance and stain positive with oil red O and Sudan black.14 Tumor cells display typical features consistent with malignancy including nuclear pleomorphism, mitotic figures, and nuclear hyperchromatism.1 Periorbital sebaceous carcinoma has a well-documented tendency to spread in a pagetoid fashion,10,11,21 with reported rates of pagetoid spread between 47% and 80%.3,19,24,59,63,64 This has obvious implications for surgical management and may explain the high rate of recurrence associated with sebaceous carcinoma relative to other skin cancers. Although extraorbital sebaceous carcinoma is not typically associated with pagetoid spread, cases of intraepithelial invasion have been reported.40,65,66 Multicentricity is another aggressive feature that has been reported in periorbital sebaceous carcinoma; lower and upper eyelid lesions occur synchronously in between 1% and 6% of patients.25,67 Tumors with a multicentric origin are at high risk for local recurrence.12,21,67 Four histologic patterns of sebaceous carcinoma are commonly recognized: lobular, comedocarcinoma, papillary, and mixed.11,12,21 Tumors may also be classified as well differentiated, moderately differentiated, or poorly differentiated; less-differentiated tumors are associated with increased mortality.21 Other histologic markers of poor prognosis include pagetoid spread, multicentric origin, tumor size >10 mm, and invasion of vascular, lymphatic, and perineural structures.11,21,68,69

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Figure 5. Histopathologic appearance of sebaceous carcinoma. (A) Hematoxylin and eosin (H&E), original magnification ·2. Irregular aggregates of basaloid epithelial cells with scant cytoplasms extend from an ulcerated epidermis into the reticular dermis. (B) H&E, original magnification ·20. The basaloid cells have vacuolated cytoplasms. There are scattered necrotic cells and mitotic figures. Photographs courtesy of Ilana Rosman, MD.

Sebaceous carcinoma may at times be difficult to differentiate from benign sebaceous neoplasms such as sebaceous adenoma, seboacanthoma, and sebaceoma, as well as other malignant neoplasms including basal cell carcinoma with sebaceous differentiation. The substantial controversy regarding the nomenclature of benign sebaceous neoplasms can add to this confusion.35,70–72 In most cases, sebaceous carcinoma can be differentiated from benign neoplasms by the malignant features detailed above; however, a recent report by Harvey and colleagues73 highlighted the high rate of interobserver variability among pathologists’ diagnoses of sebaceous neoplasms. Differentiation of sebaceous carcinoma from other malignant neoplasms may require immunohistochemistry (IHC). Immunohistochemistry has largely replaced fat stains such as oil red O, of which the sensitivity decreases after formalin fixation, in the diagnosis of sebaceous carcinoma. Historical stains that have been used in the identification of sebaceous carcinoma include EMA, BRST-1, Cam 5.2, HMFG-1 and -2, and BCA-225, all of which stain positive in sebaceous carcinoma.74–76 More recently, adipophilin and perilipin have been found to stain sebaceous neoplasms with remarkably high sensitivity and specificity.34,77,78 One study found 100% sensitivity for both stains in cases of sebaceous carcinoma78; another found adipophilin alone to have 97.1% sensitivity and 97.1% specificity for the diagnosis of sebaceous neoplasms.34 Differentiation between sebaceous carcinoma and benign sebaceous neoplasms can be assisted using IHC, with sebaceous carcinomas showing overexpression of p53 and Ki-67

much more frequently than sebaceous adenomas.55 Another recent study has suggested the use of the lipid processing proteins alpha/beta hydrolase domaincontaining protein 5 (ABDH-5), progesterone receptor membrane component-1 (PGRMC-1), and squalene synthase IHC to differentiate between benign sebaceomas and malignant sebaceous carcinomas.79 Diagnostic Workup Staging Sebaceous carcinoma is staged according to the American Joint Committee on Cancer Tumor, Node, Metastasis (TNM) classification guidelines for nonmelanoma skin cancers.80 According to these guidelines, staging of nonmelanoma skin cancers is dependent on tumor location, such that periorbital and extraorbital carcinomas are staged differently. The TNM criteria for staging of periorbital sebaceous carcinoma are summarized in Table 3. For comparison, staging of extraorbital sebaceous carcinoma is detailed in Table 4. T staging for cutaneous carcinomas surrounding the eye is adjusted to account for high-risk features unique to the periorbital region; in particular, tumors involving the tarsal plate or eyelid have a higher potential for recurrence and metastasis, and this is reflected in the staging system. N staging for periorbital cutaneous carcinomas is simplified to reflect either the presence or absence of lymph node involvement. T staging for extraorbital cutaneous carcinomas is dependent on a set of histopathologic “high-risk” features that have been associated with a worse prognosis. These features include thickness >2 mm, Clark level $ IV, perineural invasion, poorly

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SEBACEOUS CARCINOMA: REVIEW OF THE LITERATURE

TABLE 3. TNM Staging for Periorbital Sebaceous Carcinoma

TABLE 4. TNM Staging for Extraorbital Sebaceous Carcinoma

Primary tumor (T)

Primary tumor (T)

TX

Cannot be assessed

TX

To

No primary tumor

To

No primary tumor

Tis

Carcinoma in situ

Tis

Carcinoma in situ

T1

Tumor dimension 20 mm (T3 stage or higher in periorbital sebaceous carcinoma, T2 or higher in extraorbital sebaceous carcinoma). Although the rates of regional and distant metastasis seem to be declining with earlier detection and appropriate treatment,24,50,63,85,86 sebaceous carcinoma remains a potentially aggressive neoplasm with the capability to metastasize to distant sites and therefore requires vigilant follow-up. One proposed follow-up schematic includes a chest X-ray, liver function tests, ultrasound of the regional lymph nodes, and a bone scan every 3 months after diagnosis for 1 year, followed by every 6 months for another year, and then once a year.88 This approach may be burdensome for many clinicians and patients, and is likely only necessary for high-risk disease (e.g., tumor Stage T3 or higher). Development of symptoms concerning for metastasis (cough, bone pain, fatigue, weight loss) should prompt advanced imaging regardless of the follow-up timeline.

Treatment Excision Wide local excision (WLE) has been the historical standard of care for sebaceous carcinoma since

its initial description in the 1950s.1,2,20–22,35 For periorbital sebaceous carcinoma, exenteration is reserved for cases with evidence of unresectable orbital soft tissue invasion on imaging.12,24,84 Local recurrence rates for sebaceous carcinoma treated with WLE are detailed in Table 5. Overall local recurrence rates for WLE in the 1960s to 1980s were quite high (19%– 37%). It is unclear why sebaceous carcinoma has such high rates of local recurrence even after resection with adequate margins. The high rate of pagetoid spread in periorbital sebaceous carcinoma, combined with the possible multicentric nature of some tumors, may provide some explanation. Within the past 15 years, the local recurrence rate after WLE has declined (4%–28%) for both periorbital and extraorbital sebaceous carcinoma (Table 5). This may be due to increased clinician awareness of sebaceous carcinoma, leading to an overall earlier stage at diagnosis.12,27,86 In general, recurrent disease is treated with surgical reexcision. In periorbital sebaceous carcinoma, orbital invasion may have occurred, necessitating exenteration.3,21,84 Adjuvant radiotherapy can be used in patients with recurrent disease to reduce the risk of another subsequent recurrence.86 Mohs Micrographic Surgery The advent of Mohs micrographic surgery (MMS) has provided dermatologists with a reliable method for intraoperative assessment of surgical margins, resulting in superior tumor margin control while allowing for maximum preservation of healthy tissue.108 Mohs micrographic surgery is particularly advantageous for the treatment of sebaceous carcinoma given the high frequency of tumors in cosmetically sensitive areas such as the eyelids and face. Studies reporting the outcomes of MMS for sebaceous carcinoma are summarized in Table 6. Overall, MMS has been associated with lower local recurrence rates than WLE for periorbital sebaceous carcinoma.64,114,120 Although fewer studies detailing outcomes of MMS for extraorbital sebaceous carcinoma have been published, the 2012 American Academy of Dermatology Appropriate Use Criteria for MMS rated MMS as “appropriate” in all locations regardless of

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SEBACEOUS CARCINOMA: REVIEW OF THE LITERATURE

TABLE 6. Local Recurrences After MMS for Sebaceous Carcinoma

Study Harvey and Anderson8 109

No. Patients

Location

Local Recurrences

Follow-up Duration, months

3

Periorbital

0

18 30

1

Periorbital

0

Dzubow87

2

Periorbital

0

3

Ratz and colleagues110 Folberg and colleagues111

3 3

Periorbital Periorbital

0 2

29 6

Yount and colleagues112

8

Periorbital

1

57

Coldiron and Smoller113

1

Periorbital

0

48

Zurcher and colleagues83

1

Periorbital

0

2

Spencer and colleagues114

18

Periorbital

2

37

Dixon and colleagues

Snow and colleagues64

9

Periorbital

1

38

Arora and colleagues115 (slow MMS)

1

Periorbital

0

36

Callahan and colleagues84 Reina and Parry116

2 1

Periorbital Extraorbital

1 0

103 7

Thomas and colleagues117

3

Both

0

11

Berlin and colleagues118

1

Extraorbital

0

24

Both

0

44

Brady and Hurst119

37

patient type.121 It is likely that the outcomes of MMS for sebaceous carcinoma (particularly extraorbital sebaceous carcinoma) are vastly under-reported in the literature, and additional data are needed to allow for true comparison of the long-term outcomes of MMS versus WLE. The tendency for intraepithelial spread of sebaceous carcinoma presents obvious challenges for complete surgical excision. Some studies have recommended excision of an extra 4 to 5 mm Mohs layer in cases with pagetoid spread to help assure adequate excision64; others have advocated for formal assessment of the final peripheral margin with paraffin sections.111 Overall, MMS has been associated with very good outcomes for tumor control and should be considered for all patients with sebaceous carcinoma, especially those with lesions in cosmetically sensitive areas. Radiation Radiation therapy as a primary treatment modality for sebaceous carcinoma has been associated with higher rates of recurrence and mortality when compared with surgical excision.21,83,122–124 However, numerous case series and case reports have demonstrated response to radiation therapy in patients who were either poor

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surgical candidates secondary to medical comorbidities or who refused surgical treatment.9,125–129 Complications from radiotherapy performed near the eye can be quite extensive and include radiation conjunctivitis or keratitis, dermatitis, lash loss, permanent loss of visual acuity, cataracts, retinopathy, and chronic dry eye.124,127 The risk of these complications should be minimized with appropriate shielding and balanced against the obvious morbidity of orbital exenteration. Regional metastasis discovered at the time of diagnosis is typically treated with adjuvant radiation after regional lymph node dissection.3,12,27,86,88 In the case of periorbital sebaceous carcinoma, regional lymphadenectomy necessarily includes parotidectomy given the routes of lymphatic drainage of periorbital structures.94,130 A handful of case reports have been published to support the use of adjuvant radiotherapy in cases of locally advanced (Stage T3a or higher) or high-risk (pagetoid spread) periorbital sebaceous carcinoma that has not yet metastasized to regional lymph nodes.68,130,131 In general, the use of radiation therapy for sebaceous carcinoma should be restricted to recurrent lesions, metastatic disease, or palliative treatment in patients who are not candidates for surgical excision.

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Chemotherapy Reports detailing the use of chemotherapy in sebaceous carcinoma are limited to a small number of case reports.88,132–134 The most common chemotherapeutic regimens resulting in treatment response have been fluoropyrimidine based. A recent article summarizing these reports suggested that 5-fluorouracil, in conjunction with platinum-based agents such as cisplatin, is particularly effective.132 More studies are required to delineate the optimum treatment regimen for metastatic sebaceous carcinoma. Of note, the use of topical adjuvant chemotherapy for high-risk periorbital sebaceous carcinoma has been reported. A pilot study reported by Shields and colleagues5 in 2002 demonstrated complete clearing of intraepithelial pagetoid invasion after topical application of mitomycin C; 2 case reports have detailed similar results.135,136 The use of conjunctival cryotherapy at the time of surgical excision for cases with pagetoid spread has also been reported137; however, side effects including permanent loss of visual acuity, corneal ulceration, and chronic dry eye may occur.138 The use of cryotherapy is somewhat controversial and at this point is largely surgeon-dependent.12,37,136 Overall treatment recommendations are presented in Table 7.

Prognosis Historically, periorbital sebaceous carcinoma has been associated with a poor overall prognosis with reported metastasis rates between 14% and 28% and cancer-specific mortality between 18% and 30%.3,20,22 Recent studies have demonstrated much lower rates of cancer-specific mortality (between 3% and 6.7%).24,27,63,64,85 In addition to the histologic predictors noted above, poor prognostic indicators include delayed diagnosis (>6 months), increasing size (>10 mm), and involvement of both eyelids in the case of periorbital sebaceous carcinoma.21,81 The most significant predictor of reduced survival is the presence of metastatic disease at the time of diagnosis.69 Extraorbital sebaceous carcinoma has traditionally been considered as a less aggressive neoplasm when

TABLE 7. Overall Treatment Recommendations for Sebaceous Carcinoma 1. Mohs micrographic surgery is the best initial treatment modality for sebaceous carcinoma 2. Evidence of orbital invasion on imaging necessitates exenteration 3. Immunohistochemistry should be performed on all sebaceous carcinoma specimens to screen for MTS a. Patients with loss of mismatch repair on IHC require genotyping for MSI and referral to a geneticist b. Patients with personal or family history of malignancy require germ-line mutation analysis regardless of IHC or MSI results 4. Sentinel lymph node biopsy should be performed only for periorbital sebaceous carcinoma >10 mm in diameter 5. Regional metastasis is treated with regional lymphadenectomy (including parotidectomy for periorbital sebaceous carcinoma) and adjuvant radiation therapy 6. Radiation therapy is not an accepted primary treatment modality 7. Radiation therapy and systemic chemotherapy are only used for patients who are poor surgical candidates or those with recurrent or metastatic disease

compared with its periorbital counterpart.11,12,35 Recent epidemiologic data showing that extraorbital sebaceous carcinoma has a reduced tendency for regional metastasis (1.4% for extraorbital vs 4.4% for periorbital) supports this theory.69 Importantly, this difference does not seem to translate into a difference in cancer-specific mortality.69 Highly aggressive extraorbital sebaceous carcinoma has been reported in the literature,40,82,116,139–142 and regular follow-up after complete excision is still required to monitor for regional or distant metastasis. Although sebaceous carcinoma is a potentially aggressive neoplasm that requires vigilant follow-up for metastatic disease, the overall prognosis for localized disease after complete excision is good. The majority of patients with sebaceous carcinoma will die form causes unrelated to their skin cancer.24,27,63,64,69,85 Surgical excision methods that allow for maximum tissue preservation, such as MMS, provide clinicians with an opportunity to limit the morbidity associated with excision of cosmetically sensitive lesions with comparable cancer-specific mortality outcomes.

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SEBACEOUS CARCINOMA: REVIEW OF THE LITERATURE

Conclusion

15. Warren S, Warvi WN. Tumors of sebaceous glands. Am J Pathol 1943; 19:441–59.

Sebaceous carcinoma is a rare and aggressive adnexal neoplasm whose underlying pathophysiology remains largely unclear. Diagnosis requires histopathologic analysis. Although the incidence of metastasis seems to be declining, the most common site for metastasis is the regional lymph node basin. Distant metastasis to the lung, liver, bone, or brain is possible. Diagnosis of sebaceous carcinoma necessitates a workup for MTS. Personal and family medical histories, as well as IHC, are helpful in identifying patients at risk for the syndrome. Surgical excision is the primary treatment modality, with MMS likely providing superior outcomes and allowing for maximum tissue preservation. Therapies for advanced stage disease include radiation and systemic chemotherapy.

16. Anderson HL, Joseph AK. A pilot feasibility study of a rare skin tumor database. Dermatol Surg 2007;33:693–6. 17. Kwitko ML, Boniuk M, Zimmerman LE. Eyelid tumors with reference to lesions confused with squamous cell carcinoma. I. Incidence and errors in diagnosis. Arch Ophthalmol 1963;69:693–7. 18. Slutsky JB, Jones EC. Periocular cutaneous malignancies: a review of the literature. Dermatol Surg 2012;38:552–69. 19. Wolfe JT III, Yeatts RP, Wick MR, Campbell RJ, et al. Sebaceous carcinoma of the eyelid. Errors in clinical and pathologic diagnosis. Am J Surg Pathol 1984;8:597–606. 20. Ni C, Searl SS, Kuo PK, Chu FR, et al. Sebaceous cell carcinomas of the ocular adnexa. Int Ophthalmol Clin 1982;22:23–61. 21. Rao NA, Hidayat AA, McLean IW, Zimmerman LE. Sebaceous carcinomas of the ocular adnexa: a clinicopathologic study of 104 cases, with five-year follow-up data. Hum Pathol 1982;13:113–22. 22. Boniuk M, Zimmerman LE. Sebaceous carcinoma of the eyelid, eyebrow, caruncle, and orbit. Trans Am Acad Ophthalmol Otolaryngol 1968;72:619–42. 23. Dasgupta T, Wilson LD, Yu JB. A retrospective review of 1349 cases of sebaceous carcinoma. Cancer 2009;115:158–65.

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Address correspondence and reprint requests to: Eva A. Hurst, MD, Division of Dermatology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8123, St Louis, MO 63110, or e-mail: [email protected]

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