Sebaceous carcinoma

Pathophysiology

Even though the origin of ocular sebaceous carcinomas is well known (meibomian [tarsal], Zeis [eyelash], or sebaceous glands of the eyelid and caruncle), the origin of extraocular sebaceous carcinoma is less clear. The reports of sebaceous carcinoma arising within a nevus sebaceous and even in association with actinic keratosis or Bowen disease suggests that extraocular sebaceous carcinoma may originate from a pre-existing intraepidermal neoplasia, or that ultraviolet radiation plays a role in the pathogenesis of some of these tumors in sun-exposed areas. Studies have suggested a role for the Wnt/beta-catenin (a 92-kDa molecule involved in cell-cell adhesion in adherens junctions) pathway and the downstream target lymphoid enhancer binding factor-1 (LEF-1) in the pathogenesis of sebaceous carcinoma. Hypermethylation of the CDKN2A promoter region has also been found with high frequency in periocular sebaceous carcinoma occurring at a younger age.

Epidemiology

Sebaceous carcinoma is a rare tumor, with an estimated incidence rate of approximately 1 to 2 per 1 million per year. However, on the eyelid is the most common malignancy after basal cell and squamous cell carcinoma.

Although most sebaceous carcinomas occur sporadically -- in a small subgroup of patients, typically younger than 60 years -- may be a marker of MTS, an autosomal dominant disorder considered a variant of hereditary nonpolyposis colorectal cancer syndrome (Lynch syndrome), so called Lynch II. Patients with MTS can also have benign sebaceous neoplasms, as sebaceous adenoma (like the patient of the case), or sebaceous differentiation of other malignancies as basal cell or squamous cell carcinomas.

Clinical presentation

Typically sebaceous carcinoma presents as a firm, gradually enlarging subcutaneous pink to tan or yellow nodule that can be ulcerated. It occurs 80% of the time in the skin of the head or neck, involving the eyelids 40% of the time. Less frequently it can occur on the trunk or extremities, or even in extracutaneous sites, such as the parotid gland, nasal cavity, breast, large bowel, ovary, and prostate.

Regional lymph nodes are the most common site of metastasis, even though distant metastasis may involve the lung, liver, parotid gland, and bone.

Microscopic features

Hematoxylin and eosin shows neoplastic basaloid, basosquamous, or epidermoid cells with various degrees of differentiation, disposed in lobules or sheets of cells separated by a fibrovascular stroma. Well-differentiated tumors may contain sebocyte like cells with vacuolated, foamy cytoplasm. Sebaceous carcinoma usually stains negative for carcinoembryonic antigen, S100, HMB45, SOX10, CD5, GCDFP-15, D2-40, and Ber-EP4 (occasionally positive).

Prognostic and molecular features

Based on recommendations in published expert guidelines, genetic testing for MTS is recommended in patients with extraocular sebaceous carcinoma and a Mayo MTS overall risk score greater than or equal to 2. For patients with sebaceous carcinoma and suspected MTS who do not fulfill the Mayo MTS clinical criteria, immunohistochemical tumor testing for loss of mismatch repair proteins (MSH2 and MLH1) may be appropriate to identify patients who are candidates for genetic testing. Mutations of MSH2 (93% of cases) result in deficient immunostaining patterns of MSH2 and MSH6, while mutations of MLH1 (7% of cases) yield deficient staining patterns of MLH1 and PMS2.

References

6. Tripathi R, Bordeaux JS. Impact of muir–torre syndrome on survival in patients with sebaceous carcinoma: A seer population-based study. Dermatol Surg. 2019;45(1):148-149. doi: 10.1097/DSS.0000000000001503.