Sebaceous gland carcinoma: Can we do better?

Sebaceous gland carcinoma (SGCa) is the most common eyelid malignancy in India.[1] Yet, it is widely misdiagnosed and mismanaged. Delayed diagnosis and inappropriate treatment, coupled with the inherent aggressive behavior of the tumor, result in an unacceptably high incidence of local recurrence, regional lymph node metastasis, systemic metastasis, and death.[23] In an era of advanced imaging, precise microsurgery, powerful chemotherapeutic protocols, and stereotactic radiotherapy, steered by well-trained ocular oncologists and ophthalmic oncopathologists, we can certainly do better.

Diagnosis Is the Key

Over 50% of patients with nodular SGCa simulate a chalazion and those with intraepithelial (pagetoid) SGCa masquerade as unilateral blepharoconjunctivitis.[4] General ophthalmologists, being the primary point of contact, must be well aware of the clinical signs of SGCa and the red flags that tip the diagnosis. Apart from an obvious eyelid nodule extending beyond the upper edge of the tarsus (unlike a chalazion, which is limited to the tarsus), the nodular type of SGCa typically manifests with loss of eyelashes in the involved area, loss or obliteration of meibomian gland orifices, widening of the eyelid margin, abnormal vascularity of the eyelid margin, and alteration in the sharp anatomy of the posterior eyelid margin (rounding) as shown in Fig. 1.[2] Intraepithelial SGCa may or may not have an evident nodular lesion. In addition to the eyelid margin and tarsal features seen in nodular SGCa, intraepithelial SGCa is characterized by diffuse congestion and thickening of the palpebral and bulbar conjunctiva, conjunctivalization of the cornea, and thick ropy discharge [Fig. 2].[2] Meticulous attention to details and elaborate examination with a slit lamp are important to elicit some of these features. Atypical age (>40 years) for a chalazion and quick recurrence following curettage, along with any of the accompanying features listed above, warrants a high index of suspicion and referral to an expert for a protocol-based management. Any elderly patient with unilateral chronic blepharoconjunctivitis for which there is no evident cause and that does not respond to conventional treatment in a finite period also qualifies for an expert evaluation for possible map biopsy (biopsy from 17 predetermined conjunctival locations to diagnose and to meticulously determine the extent) and further management as appropriate.

Figure 1

Nodular sebaceous gland carcinoma simulating a chalazion. Picture of the everted eyelid with a nodular sebaceous gland carcinoma shows sparse eyelashes in the involved area, loss of meibomian gland orifices, widening of the eyelid margin, abnormal vascularity of the eyelid margin, and alteration in the sharp anatomy of the posterior eyelid margin (rounding)

Figure 2

Intraepithelial sebaceous gland carcinoma presenting with unilateral blepharoconjunctivitis. In addition to the eyelid margin and tarsal features typically seen in sebaceous gland carcinoma, the intraepithelial variant is characterized by diffuse congestion and thickening of the palpebral and bulbar conjunctiva, conjunctivalization of the cornea, and thick ropy discharge

Mechanical Thinking versus Customized Approach Based on Tumor Biology

”Oculoplastic surgeons think mechanical” – so said Goldberg[5] and I concur. Excellent surgical skills and the esthetic foresight that the oculoplastic surgeons are eminently endowed with must be tempered by the clinical application of standard oncological principles to optimize care and outcome in SGCa. Ten pearls that may help optimal management of SGCa are as follows:

Tumor extends beyond what is clinically evident. SGCa indeed extends beyond what is obvious on gross examination under diffuse light.[2] A careful slit-lamp examination is mandatory to determine the tumor margins preoperatively. Not just the evident tumor but also the attendant features (loss of eyelashes, thickening of the eyelid margin, loss or obliteration of meibomian gland orifices, etc.) beyond the extent of the visible tumor help determine the tumor margin for excision

Assess the posterior extent of the tumor. Simplistic assumption of the tumor extent based on what is evident from the skin results in an incomplete excision. SGCa being a tumor that arises from the tarsus, tarsal and palpebral conjunctival involvement is generally more extensive than the skin.[6] When excision is planned, each lamina must be marked separately based on the extent of involvement. Differential excision is possible, with the anterior lamina being relatively conserved (posterior laminar resection).[6] In larger SGCa, it may be difficult to evert the eyelid and preoperatively determine the posterior extent of the tumor. In such situations, the posterior extent is assessed intraoperatively. If the tumor extends into the medial canthus, then exact localization of the medial extent of the tumor may be difficult. If the tumor extends up to the lateral canthus, contiguous extension into the lacrimal grand needs to be ruled out. If the extent of the tumor cannot be clinically judged, then a preoperative high-resolution magnetic resonance imaging may help. Canthal extension is one of the major risk factors for local tumor recurrence and metastasis in SGCa[7]

Get a good view. Intraoperative hemostasis at every step of surgery and using an operating microscope provides the best visualization

No-touch technique. The surgeon should consciously avoid holding the tumor with surgical instruments and manipulation should be gentle to minimize the risk of tumor seeding

Intraoperative frozen section margin control is the key to success. Apart from the mandated 4-mm clinically clear excision margin, intraoperative confirmation of complete tumor excision by frozen section is the standard of care.[2] If frozen section is inconclusive or is not available, then confirmation of the margins by expedited fixed sections (possible within 48 h) should be followed by secondary reconstruction. The implications of unmonitored and incomplete excision include local tumor recurrence and possible metastasis, need for a second surgery, and tumor seeding if a flap is used for reconstruction

Neoadjuvant chemotherapy is an option. If the tumor is too large for safe and complete excision, then substantial reduction in the tumor size can be achieved by neoadjuvant chemotherapy before primary surgery[8]

Beware of intraepithelial extension. Patients with clinically suspected intraepithelial SGCa should be subjected to map biopsy.[2] If the extent of intraepithelial invasion is limited, complete primary excision of the suspicious conjunctiva and cryotherapy are the options[2]

Adjuvant therapy should not be guided by guess but by histopathology. Some of the indications for adjuvant therapy are intraepithelial invasion, incomplete tumor excision, tumor size >20 mm, canthal and anterior orbital extension, and histopathological evidence of perineuritic, lymphatic, or vascular invasion.[23478910] If map biopsy is positive for intraepithelial invasion up to one quadrant, adjuvant cryotherapy is an option, while for diffuse and multifocal involvement, topical mitomycin-C, plaque brachytherapy, surgical excision, and orbital exenteration may be considered. Incomplete tumor excision would necessitate re-excision if feasible or adjuvant radiotherapy. Adjuvant radiotherapy can also be considered for tumor size >20 mm, canthal and anterior orbital extension, histopathological evidence of perineuritic invasion, and for patients who undergo orbital exenteration with histopathological evidence of periosteal or bone invasion. The role of adjuvant chemotherapy is not established but could be considered in consultation with the oncologist for patients with orbital extension and those with histopathological evidence of lymphovascular invasion

Evaluation and management of regional lymph nodes improves success. Sentinel lymph node biopsy[9] or positron emission tomography scan for tumor size >10 mm, canthal and anterior orbital extension, and histopathological evidence of lymphatic invasion helps in early diagnosis of regional lymph node metastasis. Such patients are managed by neck dissection, radiotherapy, and adjuvant chemotherapy

Close follow-up. Local tumor recurrence can be a delayed manifestation and can be even in a new location (SGCa being multicentric) or in the form of intraepithelial disease. The role of strict follow-up with a keen eye for local tumor recurrence and regional lymph node metastasis cannot be overemphasized. The patient should be seen every 3 months for a year, every 6 months for 3 years, and every year thereafter.

Let the Experts Manage

SGCa is clearly not a tumor that a general ophthalmologist or an occasional oculoplastic surgeon may be able to comprehensively manage. A general ophthalmologist should be aware of the clinical manifestations of SGCa and be able to triage a suspected case quickly to an appropriate specialist. SGCa is ideally managed strictly by the protocol by a trained oculoplasty surgeon with special interest in and understanding of ocular oncology or by an ocular oncologist. Optimal combination of clinical and surgical skills, guided by sound oncological principles, could provide the best chance for local and regional tumor control and minimize metastasis and death in SGCa.