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Sebaceous Carcinoma Treatment Outcomes: A Multicenter Study

Sebaceous Carcinoma Treatment Outcomes

Sebaceous carcinoma (SC) is a rare tumor found in the sebaceous glands. The sebaceous gland is the gland that lubricates our skin. Although it can develop anywhere on the body, sebaceous carcinomas are often found on eyelids. It’s responsible for 0.7% of all cutaneous malignancies. From 2000 through 2016, the overall incidence for sebaceous carcinoma was 2.4 cases per million persons. It can also spread to other parts of your body if left untreated. The primary treatment of SC is radiotherapy.  Since SC is found in the periocular region, its lesions are often divided into periocular and extraocular SC. There’s also little evidence and literature reviews analyzing the outcome of this disease at all anatomical locations. Extraocular SC is also associated with lower metastatic potential and lower mortality in comparison to ocular SC.

Methods

A study of patients diagnosed with SC from the years 1990 and 2017 in four referral centers was performed. The study was approved by the institution’s board of review. The four referral centers included in the study were the Royal Marsden Hospital, London, United Kingdom; Netherlands Cancer Institute, Amsterdam, The Netherlands; Erasmus MC, Rotterdam, The Netherlands; and the Rotterdam Eye Hospital, Rotterdam, The Netherlands. 

Out of all the patients included, only the patients with confirmed SC were included. Clinical characteristics and patient demographics were obtained from patient files. Radical resections were defined as clear pathological margins of >1 mm. The last clinical visit or telephone call was noted as the last follow‐up date. Age was calculated from the date of diagnosis. Time to recurrence, metastasis and follow‐up were calculated after the date of first treatment. The primary treatment was noted as the first treatment after pathological confirmation of SC.

IBM SPSS statistics 25 and R (R CoreTeam, 2019) were used for the statistical analyses. Recurrence rates were calculated using the cumulative incidence curves (CICs) accounting for competing risks.  Using Gray’s test, differences between CICs were calculated. But because the sample was small in size, multivariate analyses were not conducted.  

Treatment 

Patients underwent surgical resection of their SC. Four of which with ocular SCs were treated with mitomycin eye drops. Eight of the group had immediate orbital exenteration of the eye. None of the extraocular SCs were preoperatively treated. total of 19.4% of the excisional specimens had positive microscopic margins (R1 resections)(n= 20). Four patients with incompletely excised SCs received postoperative  radiotherapy ,and eight patients  were  post-operatively treated with mitomycin C eye drops to treat the remaining conjunctival in situ growth. Five patients had pathological margins less than 1 mm and were defined as R1 resections but did not receive postoperative treatment.

Recurrence 

Of all the patients with SCs in the study, 16% had local recurrence. Half of them had previous R1 resections. The median time to recurrence was 1 year and 6 months. The cumulative incidence probability for recurrence was significantly higher for (peri)ocular tumors compared to extraocular tumors (p= 0.005), and for positive resection margins compared to clear resection margins (p= 0.001). The cumulative incidence probability for recurrence was not influenced by the size of the primary tumor (p= 0.57). Interestingly, none of the immunosuppressed patients or patients with Muir–Torre developed a recurrence.

Fifteen patients were treated surgically of which seven patients with (peri)ocular SC underwent an orbital exenteration. Local chemotherapy for the recurrent disease was used in three patients for ocular SC: mitomycin C eye drops (n= 2) and interferon eye drops(n= 1). Postoperative radiotherapy for recurrence was used in two patients. Two patients did not want any further treatment for their recurrent disease, due to age and comorbidities. The 5‐and 10‐year cumulative incidence for recurrence was 15.3% and 21.3%, respectively.

Results 

The study used 100 patients with 103 SCs. Most patients were treated in the Rotterdam Eye Hospital (N= 39), followed by the Erasmus MC (n= 30), the Netherlands Cancer Institute (n= 18), and the Royal Marsden Hospital (N= 16). The median age was 72 years(range, 15–95) with a median follow‐up of 52 months (interquartile range [IQR], 24–93). A total of 57 patients were male (57%) and most were located in the periocular region (50.5%) followed by head and neck locations (32.0%). Seven patients had SCs located on the trunk (6.8%), seven on the extremities (6.8%), and two SCs were located in the genital region (1.9%). 

Seven patients were proven to have Muir–Torre syndrome (7%), with a total of 9 SCs, almost all extraocular SCs (n= 8). One patient aged 15 had a concurrent diagnosis of xeroderma pigment-to sum. Two patients required long‐term immunosuppressive drugs for kidney and heart transplantation. Three patients had a history of the hematological disease, and 17 patients had a history of other skin cancers (16%), of which three patients had a history of melanoma and one patient had a Merkel cell carcinoma.

Data concerning the differentiation grease and thickness were only available for a limited number of patients. Fourteen (of 38) patients had a well‐differentiated SC(36.8%), 8/38 a moderately differentiated (21.1%), and 16/38 patients had a poorly differentiated SC (42.1%). The median thickness was 5 mm (range, 1.2–11). The extraocular tumors were significantly larger than the ocular tumors (p< 0.001) and showed a trend towards more male prevalence (p= 0.07). 

Discussion

The outcome is based on the multicenter study of 103 SC. Periocular tumor location and positive resection margins were described as risk factors for local recurrence. The study used a total of nine patients who developed metastases with tumors less than one centimeter. 

All primary SCs were treated with excision which is in line with the published literature defining surgery as the golden standard wherein a surgical margin of at least 5 mm is advised for the ocular SCs. SC is thought to occasionally display skip areas histologically, and because the Mohs technique relies on contiguous growth, theoretically, wide excision with 5‐to 6‐mm margins in all cases might provide a higher cure rate. However, wide surgical margins conflict with the aim to preserve a functional eye. At present, no guidelines or recommendations for the width of the surgical margin for extraocular SC are available. 

The results support higher local recurrence rates after positive resection margins for periocular SCs. All published literature on risk factors for recurrences is based on ocular SCs found a recurrence rate of 16. 6% for extraocular SC without analyzing risk factors for recurrence. 

Conclusion 

SC is a rare and aggressive tumor affecting the elderly patient population. The study also found that patients with positive resection margins and periocular tumor location were more frequently associated with local recurrence. Patients with SC also are infrequently present with locoregional or distant metastases resulting in good overall survival. 

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