Melanomas: Clues to Severity

MELBOURNE, Australia, Dec. 18 -- Primary cutaneous melanomas that grow rapidly appear to correlate with a more dire prognosis, reported investigators here.

On the other hand, clinical features generally thought to signal more advanced lesions -- such as irregular borders, uneven coloring, and asymmetry -- were associated with slower tumor growth, reported Wendy Liu, M.B.Ch.B., Ph.D., of the Alfred Hospital Melbourne, and colleagues.

Faster-growing tumors occur more frequently in men older than 70, and in patients with fewer nevi, and fewer freckles, the investigators wrote in the December issue of the Archives of Dermatology.

"Special attention should be given to the promotion of awareness of the clinical characteristics of rapidly growing melanomas, such as symmetry, elevation, amelanosis, border regularity, and symptoms," they wrote.

"Lack of awareness of the features associated with rapidly growing melanomas among health care practitioners frequently leads them to inappropriately reassure patients about their lesions. The penalty associated with diagnostic delay is particularly severe with a rapidly growing melanoma."

An association between differential growth rates of primary cutaneous melanomas and varying degrees of disease severity was first described by investigators in 1969, who determined that nodular melanomas grow most rapidly, followed by superficial spreading melanomas, and lentigo maligna melanomas.

"Since then, many attempts have been made to assess the rate of tumor proliferation using various biological markers, including mitotic rate, ulceration, Ki67, cyclins, and cyclin-dependent kinase inhibitors such as p16 and p27." Dr. Liu and colleagues wrote, "Despite these attempts, little information is available on the rate of growth of primary cutaneous melanomas."

The investigators conducted a study of growth rates of melanomas to see if they could identify specific clinical associations of rapid growth.

They enrolled 404 consecutive patients with invasive primary cutaneous melanomas. The patients were interviewed in person, or over the telephone by trained interviewers, and were asked about demographics, risk factors, sun exposures, and tumor characteristics at presentation, such as pigmentation, shape, symmetry, border, texture, and symptoms such as bleeding, itching, and, change in sensation. Patients were also asked whether they themselves, a relative or friend, or a physician first detected the lesion, and how visible it was to them.

Melanoma rate of growth was assessed by asking the patients to recall the date they first noticed a lesion on the skin surface from which the melanoma later developed, and the time they first noticed that the lesion had changed or became suspicious. The time of excision was determined from the pathology report.

The main study outcome was a surrogate for rate of growth in primary invasive melanoma, calculated as the ratio of Breslow thickness to time to melanoma development.

They found that about a third of the melanomas (31%) grew 0.5 mm per month or more. The median monthly growth rate was 0.12 mm for superficial spreading melanomas, 0.13 mm per month for lentigo maligna melanomas, and 0.49 mm per month for nodular melanomas.

Rapid tumor growth was associated with tumor thickness, mitotic rate, male gender, age 70 years and older, and fewer melanocytic nevi or freckles.

Rapidly growing tumors were significantly more likely to be symmetrical, elevated, amelanotic, have regular borders, and to be symptomatic, the investigators found.

"When we combined the features of irregular border, irregular color, and asymmetry as features of 'bad-looking' melanomas, the bad-looking melanomas were associated with slower rates of growth compared with those that were not bad looking," the authors noted

The investigators acknowledged that their findings were limited by the use of patient recall to assess tumor growth rate, but pointed out that it would be both unethical to merely observe tumors without therapy in a prospective cohort study, for example.

In an accompanying editorial, Dan Lipsker, M.D., Ph.D., of Strasbourg, France, said that the study made a significant contribution to the understanding of differential growth rates in malignant melanoma.

"Every physician can probably remember patients with thick melanomas (>2 mm) who claimed that at the site of their melanoma there was no lesion two or three months ago," he wrote. "Some physicians will regard these stories with disbelief or skepticism. Other physicians, strongly involved in the care of patients with primary melanomas, will hear such stories often enough to become seriously concerned about their reality. However, until this work by Liu et al, there was no reliable data about the frequency of this event or the clinical appearance of such lesions."

The study by Dr. Liu and colleagues was supported by the Melbourne Research Scholarship from the University of Melbourne and by a research grant from the Australasian College of Dermatologists. Neither the authors nor Dr. Lipsker disclosed any financial conflicts.