Maximizing margin's meaning for melanoma

November 1, 2005

Atlanta — Recent developments in melanocyte-specific immunohistochemical stains are again proving that this technology, along with the proper technique, can enhance sensitivity in differentiating malignant melanoma from nevi in diagnostic specimens as well as in the interpretation of Mohs margins, according to Dirk M. Elston, M.D., here at the American Society for Dermatologic Surgery — American College of Mohs Micrographic Surgery and Cutaneous Oncology combined annual meeting.

"Without immunostains, frozen sections of melanoma margins can sometimes be difficult to interpret," says Dr. Elston, a staff dermatologist and dermatopathologist at Geisinger Medical Systems in Danville, Pa.

"Alternatively, the slow Mohs technique offers better tissue preservation, but does not show the true surgical margin."

A true peripheral margin can be evaluated when a diagnosed melanoma is excised in a conventional Mohs fashion. In this setting, immunostains can be helpful in facilitating the interpretation of the margin.

While the stain S-100 is still sometimes used, it has been largely replaced by Mart-1 and Melan-A antibodies. The relative sensitivity of the immunostain S-100 is useful in some settings, but the stain is nonspecific and identifies dendritic stains such as Langerhans cells, Dr. Elston says. This background staining can make interpretation difficult, although the newer stains are more specific, he explains.

"In terms of the diagnosis of melanocytic lesions, the new stain S-100 A6 is helpful in some settings. It stains Spitz nevi diffusely, melanoma in a patchy fashion and benign ordinary nevi often not at all," Dr. Elston says. "Together with MIB-1 and HMB-45 staining, they can be helpful in diagnosing difficult Spitzoid lesions. MIB-1 is a proliferation marker and loss of HMB-45 staining in the deeper portions of the lesion is a sign of maturation.

"When using HMB-45, we now know that it's not the presence or absence of staining in the lesion, but the pattern of staining that holds important details," Dr. Elston says. "For instance, a top-heavy pattern is typical for a nevus, while a top-to-bottom pattern is typical for melanoma. The stain MIB 1 indicates cells synthesizing DNA in the cell cycle. The interpretation is similar to the interpretation of mitoses, and MIB-1 can be regarded as a surrogate marker for mitoses.

"Any area where mitoses are worrisome, MIB-1 positivity is worrisome. At the junction, this is not a great concern, but at the deep component of the lesion, these readings are significant," Dr. Elston says.

Technical details

Although it is clear that each new development among existing and novel immunostains is invaluable to the future of deciphering tumor sections, their effectiveness may be insignificant without proper excision technique.

"A recurring problem is the patient speckled with nevi and lentigines. While it would be best never to cut through a benign pigmented lesion in the margin, this is not always possible," Dr. Elston says. "If you do, indicate to the pathologist that you have done so by marking the benign area, such as a distinct dark freckle, within the margin by using green Mohs ink to dot the surface of the site - this will survive processing and make interpretation easier for the pathologist."

Fine-tuning one's understanding of a patient's sun damage background can also aid the Mohs surgeon in proper excision, as well as prevent them from over-reading the slide's message, Dr. Elston explains. Heavily sun-damaged skin has a high melanocytic density, with every other basal nucleus possibly being melanocytic.

"When used properly, immunostains offer better sensitivity and specificity for diagnoses of melanoma," Dr. Elston says.