Dermal appendages of the eyelid include sebaceous glands, sweat glands, and hair follicles (see the section Topography, earlier in the chapter). They are also referred to as adnexal appendages, which, in this context, refers to skin appendages that are located within the dermis but communicate through the epidermis to the surface. Although meibomian glands technically are not dermal appendages, they are modified sebaceous glands embedded in the tarsus and may give rise to some of the neoplasms discussed in the following subsections, particularly sebaceous carcinoma.
Syringoma
Syringoma, a common benign lesion derived from sweat glands, can occur in the eyelid, usually the lower eyelid, typically manifesting clinically as multiple tiny flesh-colored papules. Syringomas result from a malformation of the eccrine sweat gland ducts. Histologically, syringomas consist of multiple comma-shaped and/or round ductules lined with a double layer of epithelium and containing a central lumen, often with secretory material (Fig 13-21).
Sebaceous hyperplasia
Sebaceous hyperplasia is an uncommon benign lesion of the eyelid and face. Clinically, it appears as a small, yellow papule. Histologically, it is typically a single, enlarged sebaceous gland with an increased number of glandular lobules attached to a single central duct (Fig 13-22).
Sebaceous adenoma
Sebaceous adenoma is a benign lesion of the skin that can occur on the eyelid, though rarely. Sebaceous adenoma typically manifests as a circumscribed yellowish nodule. Histologically, it is composed of multiple sebaceous lobules that are irregularly shaped and incompletely differentiated (Fig 13-23). The possibility of Muir-Torre syndrome (a subtype of Lynch syndrome, a hereditary cancer syndrome) should be considered when sebaceous adenoma is diagnosed, as it is the most common sebaceous neoplasm in this syndrome (see Table 13-2). Immunohistochemistry for DNA mismatch repair proteins may be useful in screening for cancer syndromes.
Sebaceous carcinoma
Sebaceous carcinoma is a malignancy with a propensity to occur on the eyelids. It most commonly involves the upper eyelid of individuals older than 65 years. It may originate in the meibomian glands of the tarsus, the glands of Zeis at the eyelid margin, or the sebaceous glands of the caruncle. Sebaceous carcinoma may be more common than SCC on the eyelid; however, the diagnosis is often missed or delayed because of this lesion’s tendency to mimic other conditions, such as a chalazion or chronic unilateral blepharoconjunctivitis (Fig 13-24).
Histologically, well-differentiated sebaceous carcinomas are readily identified by the microvesicular foamy nature of the tumor cell cytoplasm, which resembles mature sebocytes. Moderately differentiated tumors may show some sebaceous features (Fig 13-25). Poorly differentiated tumors, however, may be difficult to distinguish from other, more common malignant epithelial tumors such as SCC or BCC. Special stains, such as oil red O or Sudan black B, may be used to diagnose sebaceous carcinomas because they reveal lipid within the cytoplasm of tumor cells. Tissue staining for lipids is performed on frozen tissue sections because the lipid constituents are often removed during paraffin processing. When sebaceous carcinoma is suspected clinically, the pathologist should be alerted so that tissue handling allows for any special stains needed. However, these stains are rarely used in clinical practice because of the technically difficult staining procedure. Although a variety of immunohistochemical stains have been investigated for their specificity in identifying sebaceous carcinoma, there is no single antibody or combination of antibodies that can consistently identify these tumors. An expert evaluation by an experienced pathologist may be required for an accurate diagnosis.
A primary characteristic of sebaceous carcinoma is pagetoid spread, the dissemination of both individual tumor cells and small clusters of tumor cells within the epidermis or conjunctival epithelium (see Fig 13-25B). The pagetoid areas do not have a direct connection to the main portion of the tumor. Another characteristic is the complete replacement of conjunctival epithelium by tumor cells, or sebaceous carcinoma in situ (see Fig 13-25C). This particular characteristic may make complete excision of sebaceous carcinoma challenging.
Treatment of sebaceous carcinoma typically involves wide local excision of the tumor. Widespread conjunctival epithelial involvement or deeply invasive tumors may require exenteration. Because it can be difficult to identify pagetoid spread or sebaceous carcinoma in situ on frozen sections, permanent sections are generally considered more reliable for evaluation of surgical resection margins than frozen sections of margins or Mohs technique. Before definitive excision, staging of tumor extent via routine processing of multiple small “map” biopsies, typically of the conjunctiva, may afford a more accurate assessment of the extent of spread of the carcinoma and, therefore, of the type of excision that is most appropriate for the patient. Adjunctive therapies for sebaceous carcinoma include the use of topical chemotherapy, cryotherapy, and radiotherapy.
Survival rates for patients with sebaceous carcinoma are worse than those for patients with SCC, but they have improved in recent years as a result of increased awareness, earlier detection, more accurate diagnosis, and more appropriate treatment. Typically, survival correlates with size and extent of the primary tumor. Spread of tumor may be local with direct invasion into the orbit and other adjacent structures. As metastases first involve regional lymph nodes, sentinel lymph node biopsy can be useful in tumor staging. Distant metastasis of tumor, usually to the liver and lung, may occur in rare cases.
Excerpted from BCSC 2020-2021 series: Section 4 - Ophthalmic Pathology and Intraocular Tumors. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.