Oil Red O, are useful in making this diagnosis and require that surgical specimens be sent for pathological analysis as fresh tissue and not fixed in formalin (Fig. 9.3b, c).

There is a significant risk of metastasis with sebaceous gland carcinoma; therefore, a systemic workup is suggested for most new cases. The estimated risk of nodal metastasis and distant organ metastasis is 10–15%. The most likely sites of metastasis include the lung and the liver. Unlike melanoma, where depth of invasion is correlated with metastatic spread of the cancer, depth of invasion does not appear to correlate with metastatic spread. Rather, tumor size appears to correlate with the metastatic spread of sebaceous gland carcinoma, although to date there are no studies that specifically look at high-risk histologic features that correlate with metastatic behavior.

9.2.5 Other Primary Eyelid Malignancies

There are a number of other cancers that can occur in the eyelids, all of which are very uncommon. Because the periocular region is rich with glandular structures, a number of adenocarcinomas can develop in the eyelid in addition to sebaceous gland carcinoma. These include mucinous sweat gland adenocarcinoma [8, 9], adenocarcinoma of the gland of Moll [10–12], and adenoid cystic carcinoma [13].

Lymphomas can present in the eyelid, but this most frequently occurs in cases where there is already systemic involvement [14]. Both B- and T-cell lymphomas can be seen in the eyelid.

Sarcomas of the eyelid are rare. In a study of non-BCC and non-SCC eyelid tumors, sarcomas accounted for 12% of the cases. Kaposi sarcoma is the most common type seen in the eyelid, usually in patients with HIV/AIDS [15]. Angiosarcoma is the second most common sarcoma affecting the eyelid [16].

Merkel cell carcinoma is a rare skin cancer thought to arise from mechanoreceptors of the same name. Merkel cell carcinomas exhibit neuroendocrine differentiation and are most commonly seen in the head and neck. Typically they present as firm, purple nodules (Fig. 9.4). These tumors have a high rate of nodal metastasis, with between 15 and 66% having nodal disease at presentation [17, 18]. Recently, a polyomavirus has been implicated as a causative agent in this disease [19].

9.3 Management

Although evaluation and management of some eyelid malignancies is relatively straightforward, a significant proportion of the eyelid cancers seen at a referral cancer center require a comprehensive multidisciplinary approach, often involving consultation with the disciplines of medical oncology, radiation oncology, surgical oncology, radiology, and pathology.

Fig. 9.4 Clinical photograph of Merkel cell carcinoma of the eyelid

9.3.1 Evaluation

Evaluating a patient with an eyelid cancer requires taking a thorough history and performing a complete ophthalmic examination. Prior history of skin cancer and sun exposure are important details to note. Attention to the size and location of the tumor is critical in planning the appropriate treatment. Palpation of the lymph nodes in the preauricular, submandibular, and cervical regions is important in assessing for nodal metastases. The use of American Joint Committee on Cancer staging, while not widely practiced, has been recommended for eyelid carcinomas [20]. The presence of an eyelid skin cancer should prompt the search for skin cancers elsewhere. A full-body skin examination by a dermatologist should be recommended. Orbital imaging, usually magnetic resonance imaging, is necessary for tumors with a propensity for orbital invasion. This modality can also help in identifying perineural invasion, a high-risk characteristic seen in certain tumors.

In cases of more aggressive malignancies, radiologic studies to assess for lymphatic spread and metastases are necessary. Ultrasound evaluation of the neck to assess for suspicious nodes should be performed for most cancers other than BCC, including melanoma and sebaceous gland carcinoma. Any concerning nodes should be subjected to fine-needle aspiration biopsy.

Metastatic workup with a chest X-ray and liver function testing should also be performed for most cancers other than BCC to establish a baseline and assess for lung and liver involvement. In the case of sebaceous gland carcinoma, gastrointestinal and gynecologic evaluations should be performed as well because of the rare association with Muir–Torre syndrome.

9.3.2 Tumor Excision and Eyelid Reconstruction

Surgical excision of eyelid cancers is certainly the most common treatment, but other modalities play a role. Ultimately, the treatment plan depends on the type, location, and extent of disease. If there is uncertainty about the diagnosis, an incisional biopsy, shave biopsy, or punch biopsy can be performed.

The standard treatment for most eyelid malignancies is excision with a margin of normal tissue [21]. This can be accomplished by excision with either intraoperative frozen section analysis or permanent section evaluation to confirm negative margins or by Mohs micrographic surgery. In our practice, the majority of tumors are excised with intraoperative frozen section analysis with review of the sections performed together by the surgeon and an experienced dermatopathologist. For BCC and SCC, typically a 2-mm margin of uninvolved tissue is removed. If necessary, additional tissue is removed until the margins are sufficiently clear. Not surprisingly, incomplete excision is associated with a significantly higher rate of recurrence [21]. In the case of melanomas, wider margins—usually 4 mm— are taken. Additionally, frozen section analysis is not reliable for melanomas. Depending on the situation, either reconstruction of the eyelid is performed immediately after removal of a melanoma, with plans to remove more tissue if necessary when permanent pathology results are available, or the reconstruction is performed the following day once permanent section evaluation of margins is complete.

Mohs micrographic surgery is a technique for excision and analysis of skin cancers employed by specially trained dermatologists. During Mohs surgery the dermatologist excises the tumor and then examines frozen sections of the margin in an en face manner. The area is carefully mapped so that additional tissue can be removed from areas with a positive margin. This technique is useful for lesions in certain areas to minimize the amount of tissue removed. It has been shown to be extremely effective in treating periocular BCC, both primary and recurrent lesions [22]. It is not, however, appropriate for excision of melanocytic lesions unless a “slow Mohs” technique with paraffin sections is used. Unlike traditional intraoperative frozen section analysis, in Mohs micrographic surgery the pathologic tissue analysis is performed by the dermatologist.

For advanced eyelid tumors that are invading the orbit or the globe, exenteration may be necessary for local control of disease. In a very large series of 429 orbital exenterations, 40% were performed for eyelid tumors [23]. BCC accounted for 90% of these [24]. Our experience at M.D. Anderson Cancer Center suggests that some invasive eyelid tumors that would typically be treated with an orbital exenteration