Poor differentiation, MTS spark concerns with sebaceous carcinoma

Denver - In diagnosing and treating sebaceous carcinoma, poorly differentiated tumors carry a poor prognosis, and the presence of Muir Torre syndrome (MTS) brings additional cancer risk, according to an expert.

Because sebaceous carcinoma most commonly presents on the eyelids, says Allison Hanlon, M.D., Ph.D., “There often is a delay in diagnosis. This can have a negative outcome for patients.” She is assistant professor of dermatology at Yale University School of Medicine, New Haven, Conn. Dr. Hanlon spoke recently at the annual meeting of the American Academy of Dermatology.

Typically, sebaceous carcinoma presents in Caucasian patients, who in a large Surveillance, Epidemiology and End Results (SEER) review accounted for 86.2 percent of cases (Dasgupta T, Wilson LD, Yu JB. Cancer. 2009;115(1):158-165), Dr. Hanlon says. Additional risk factors include previous radiation therapy and perhaps immunosuppression, she adds.

“MTS is associated with sebaceous carcinoma. When you diagnose a patient with sebaceous carcinoma, first perform the evaluation for MTS, an autosomal dominant genetic syndrome that stems from a defect in the mismatch repair proteins involved in DNA repair,” Dr. Hanlon says.

Patients with MTS not only develop sebaceous carcinomas, keratoacanthomas and seboacanthomas, but visceral malignancies as well.

“The visceral malignancies can present either before or after the cutaneous findings,” she says. “And the age at presentation of the first malignancy can range. So your index of suspicion should be high, especially in a young patient who may already have developed a visceral cancer.”

Next: How to evaluate for Muir Torre syndrome

MTS evaluation

Immunohistochemistry (IHC) of sebaceous tumors, with antibodies to detect the MutS homolog (MSH) 6, MSH2 and MutL homolog (MLH) 1, can provide an efficient way of initially evaluating patients for MTS.

“As always with IHC, positive predictive value varies, ranging anywhere from 33 percent to 88 percent,” Dr. Hanlon says. “So even if IHC suggests a patient does not have MTS, you still must do additional studies. But it allows you initially to have an idea - especially if the patient had a defect in the mismatch repair proteins picked up by IHC.”

Checking for microsatellite instability (through IHC of the biopsied skin specimen or through fluorescence-based polymerase chain reaction/PCR and mutational analysis) also helps establish a diagnosis of MTS, Dr. Hanlon says.

“Microsatellites are normally and commonly repeated sequences in DNA. Mutations in DNA repair genes result in the accumulation of errors in these microsatellites. The instability refers to the appearance of either abnormally long or abnormally short sequences,” she says.

If the patient has microsatellite instability, as well as a positive family history of MTS, “Talk to the patient and the patient’s primary care provider about cancer surveillance. Ensure that patients are aware that they need to be monitored on a regular basis for the malignancies associated with MTS.”

In patients with microsatellite instability, she adds, one also can use exome sequencing to determine whether the patient has a genetic mutation.

“Unfortunately, that won’t give you the answer for all patients because the mutations can vary in any one of those proteins (MLH1, MSH6 and MSH2) that binds to the DNA,” Dr. Hanlon says. “Therefore, looking for positive family history is important, because of MTS’s autosomal dominant nature.”

Next: Best option for treating sebaceous carcinoma

Sebaceous carcinoma treatment

To treat sebaceous carcinoma, Dr. Hanlon says, “The treatment of choice is surgical - whether it be excision or Mohs micrographic surgery, depending on the tumor location and patient’s overall health.”

The SEER review showed that whether patients underwent local excision, wide local excision (with greater than one cm margins) or Mohs surgery made no difference in disease-specific survival. However, notes Dr. Hanlon, only 9 percent of patients in this series underwent Mohs surgery.

In a more recent study, half of the 52 patients with sebaceous carcinoma underwent Mohs surgery, and of this group, only one experienced a recurrence, versus two recurrences among the remaining patients, who underwent wide local excision and biopsy (Hou JL, Killian JM, Baum CL, et al. Dermatol Surg. 2014;40(3):241-246).

Additionally, the SEER study showed that histology plays an important role in determining which tumors likely will behave more aggressively, Dr. Hanlon says. As in other cutaneous malignancies such as squamous cell carcinoma (SCC), “There was a significant difference in disease-specific survival in patients with poorly differentiated tumors versus well-differentiated tumors.”

In the SEER sample, however, researchers observed distal metastases in only nine of 74 patients, and only around 50 patients had either sentinel lymph node or cervical lymph node dissection.

Related: Surgery still standard of care for sebaceous carcinoma

“Those patients who did have either distal metastases or lymph node involvement had a very poor prognosis. Even with one node involved, overall DSS was much lower.” Other factors associated with a poor prognosis include tumor size and depth of invasion and older patient age at diagnosis, Dr. Hanlon says.

Sentinel lymph node biopsy (SLNB) remains controversial in sebaceous carcinoma, mostly because it’s very difficult to determine which is the draining lymph node, especially in the head and neck, according to Dr. Hanlon. In considering whether to use SLNB, “Think about the overall anatomical location, as well as the pathology. Poorly differentiated tumors or eyelid tumors may drive one to perform SLNB. But again, evidence for that is very thin.”

Adjuvant radiation also may play a role in treating sebaceous carcinomas, she says. To monitor for recurrences, “Ultimately, close clinical follow-up is important,” Dr. Hanlon says.

Disclosures: Dr. Hanlon reports no relevant financial interests.

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