Uncommon tumors require multifactorial analysis

Miami Beach, Fla. – Treating uncommon tumors that present in a Mohs surgical unit requires matching the tumor’s clinical history and histopathology with available therapies, says an expert who spoke at the 71^st annual American Academy of Dermatology meeting.

Desmoplastic trichoepitheliomas (DTE) present as firm erythematous to white papules and grow slowly, usually on the cheek of young women, before stabilizing, says J. Suzanne Mosher, M.D., director, Mohs microsurgery, Harvard Vanguard Medical Associates, Watertown, Mass.

Differentiating between DTEs and microcystic adnexal carcinomas (MAC), as well as desmoplastic basal cell carcinomas (BCCs), can present a challenge, particularly in superficial biopsies, she says. DTE’s histologic characteristics include narrow strands of basaloid tumor cells, as well as keratinous cysts and desmoplastic stroma. The tumors include follicular or sebaceous differentiation, and typically occur in the upper two-thirds of the dermis. MACs, on the other hand, have predominantly ductal differentiation, perineural invasion, and cells that penetrate deeply into the reticular dermis and subcutaneous fat, Dr. Mosher says.

DTE debate

MACs tend to present on the lips or chin (predominantly on the left side), typically in older white females. Both MAC and morpheaform/desmoplastic BCC can include perineural invasion, she adds, but the former has fibrous stroma and progressively smaller basaloid strands with depth, while the latter has sclerotic stroma.

MACs typically grow slowly, she says, though they can be locally aggressive, invading underlying soft tissue, muscle and bone. Immunohistologically, MAC and desmoplastic BCC stain negative for the Merkel cell marker CK20, while DTE stains positive.

“There is debate among Mohs surgeons over the approach to DTE,” Dr. Mosher says, in large part due to the concern that superficial biopsies may miss a deeper component that later proves to be consistent with MAC. Given that DTE is an indolent tumor, she says, many argue for narrow excision of DTE (Merritt BG, Snow SN, Longley BJ. Cutis. 2010;85(5):254-258).

Other experts recommend Mohs surgery, partly due to DTE's predilection toward cosmetically sensitive areas, its potential display of neurotropism, or the number of cases that have been originally diagnosed as DTE, and subsequently found to be MAC (Jedrych J, Leffell D, McNiff JM. J Cutan Pathol. 2012;39(3):317-323; McCalmont TH, Humberson C. J Cutan Pathol. 2012;39(3):312-314).

In comparison, Dr. Mosher says, the literature strongly supports the use of Mohs for MAC and morpheaform BCC, because Mohs surgery offers considerably lower recurrence rates than standard excision.

“Deep diagnostic biopsy may be helpful in showing the architectural pattern and perineural invasion (PNI) of suspected adnexal tumors,” Dr. Mosher says. Mohs surgery appears reliable for treating primary, treatment-naïve MAC, she adds. “The literature suggests that previous surgery or PNI may increase the risk of persistent tumor. In such cases, some have advocated performing slow Mohs, or alternatively, standard Mohs with frozen sections to clearance of tumor, followed by a final layer for paraffin-embedded sections (Palamaras I, McKenna JD, Robson A, Barlow RJ. Dermatol Surg. 2010;36(4):446-452). Periocular MAC associated with PNI is particularly likely to persist, including after Mohs surgery.”

Diagnostic difficulties

Dr. Mosher also says that difficulties can arise in the diagnosis and treatment of atypical fibroxanthomas (AFX) and pleomorphic undifferentiated sarcomas, (previously classified as malignant fibrous histiocytomas/MFH).

AFX is a cutaneous sarcoma of mesenchymal origin that typically affects men in their 70s and usually appears on the ears, nose or cheeks. Wide local excision has traditionally been the treatment of choice for AFX, Dr. Mosher says. However, the large margins sometimes required also make AFX well-suited to Mohs surgery, which offers a 3 percent recurrence rate at 30 months (versus 10 percent recurrence rates with wide local excision). Performing sentinel lymph node biopsy (SLNB) has been advocated for recurrent tumors or those that extend deeply, she says.

“Radiation is not a viable treatment option, because you can induce aggressive changes,” Dr. Mosher says.

Pleiomorphic undifferentiated sarcoma/MFH typically affects males age 50 to 70, with tumors appearing most frequently on the head and neck. “Pleomorphic undifferentiated sarcoma/MFH also occurs more frequently on upper extremities than on lower. Distal tumors have better prognosis than proximal ones, which tend to be bigger,” she says.

The origin of pleomorphic undifferentiated sarcoma/MFH remains a mystery, according to Dr. Mosher. Experts believe it derives from mesenchymal progenitor cells, making it a true sarcoma, she adds. Moreover, “There are many reports of these arising from surgical sites or burns, so it may be an aberrant reaction to trauma. Ionizing radiation also is believed to play a role.”

Pleomorphic undifferentiated sarcomas collectively have a 71 percent recurrence rate and a metastatic rate of 44 percent.

“Of the five current subtypes, the storiform-pleomorphic subtype, with its whorled pattern, pleomorphic cells, and bizarre-looking nuclei may be cellularly indistinguishable from AFX,” she says. “This can create difficulty in management after superficial biopsies, given the rather indolent course of AFX and the potentially devastating outcomes that can be associated with MFH.

“Immunohistochemistry and gene rearrangement studies may help distinguish between AFX and

pleomorphic undifferentiated sarcoma/MFH. In AFX, mutations tend to occur more often in the p53 gene. Similarly, people with xeroderma pigmentosum (XP) have defective DNA repair genes and frequently have p53 mutations in tumors. Interestingly, four pediatric XP patients have been reported to develop AFX (Marcet S. Dermatol Ther. 2008;21(6):424-427).”

In MFH, mutations tend to occur in the KRAS and HRAS oncogenes, she adds. Dr. Mosher recommends Mohs surgery with SLNB for all MFH cases. “Overall, five-year survival is around 50 percent. Adjuvant chemotherapies are being explored to improve long-term survival.”

Disclosures: Dr. Mosher reports no relevant financial interests.