Tumor behaviors may flag high-risk BCC

Chicago - One day, dermatologists might be able to recognize high-risk basal cell carcinoma (BCC) not only by its clinical and histologic characteristics, but also by its expression of molecular biomarkers.

Presently, dermatologists recognize features including tumor recurrence, location (eyelid, lip, nose, ears), size (>2 cm) and appearance (ill-defined borders, multicentricity, radiation) as characteristics of particularly high-risk BCCs.

"Ultimately," Desiree Ratner, M.D., says, "molecular biomarkers may help us to determine which BCCs have the potential to behave aggressively. We can recognize certain high-risk features clinically and histologically, but in the future there may be other ways to identify biologically aggressive tumors early on in their clinical course." Dr. Ratner is director of dermatologic surgery and George Henry Fox associate clinical professor of dermatology at Columbia University Medical Center of the New York Presbyterian Hospital.

Dr. Ratner elaborates, "The reason that this is important is that aggressive or high-risk BCCs are associated with greater subclinical extension. They have a greater risk of locally invasive and destructive behavior as well as of recurrence, and may, if untreated or incompletely treated, carry an increased risk of metastasis. Even though metastasis is unusual for BCC, large, ulcerated or recurrent tumors tend to be the ones that ultimately metastasize."

Aggressive histologic subtypes of BCC include morpheaform, infiltrative, micro-nodular, desmoplastic and basosquamous lesions.

"Histologically aggressive BCC subtypes are associated with greater local extension and invasion, and higher recurrence rates," Dr. Ratner tells Dermatology Times. "The histologic growth pattern is just one element that reflects the biologic behavior. Although one day we may have molecular markers to help us with this, aggressive histology is in some instances as close as we can get now to identifying potential for aggressive biological behavior. We see the aggressive growth pattern microscopically, and we know that histologic subtype correlates with greater subclinical extension - these tumors invade deeply, they can track along nerves, blood vessels and fascial planes, and tend to extend much further than tumors without an aggressive histologic growth pattern."

Perineural BCC, she adds, occurs in about one percent of all BCCs and up to 10 percent of histologically aggressive BCCs. It appears most commonly in cheek and preauricular tumors and is frequently asymptomatic. Even in patients with known clinical or histologic evidence of perineural disease, no perineural invasion is detected on imaging studies in 48 percent of cases (Williams LS et al. Int J Radiat Oncol Biol Phys 2001;49:1061-1069).

Dr. Ratner says, "Perineural BCC is particularly tricky to manage because skip areas along nerves are common. Even if one is tracking the tumor out histologically, there may be an area of perineural involvement that isn't visualizable on the slide. So one may think it's all out when in reality, there's tumor just beyond where you were looking along that nerve. The question then arises, does one have to treat perineural BCC with something beyond surgery?"

Presently, Mohs micrographic surgery represents the treatment of choice for aggressive growth pattern and other high-risk BCCs, in part because this technique allows surgeons to trace out peripheral and deep tumor extensions with 100 percent margin control.