MADRID — The size and location of any microscopic metastatic deposits within the sentinel lymph node is an important predictor of prognosis in patients with cutaneous melanoma.
This conclusion is based upon detailed pathologic examination of 2,203 sentinel lymph nodes (SLNs) from 1,417 patients with cutaneous melanoma at MD Anderson Cancer Center in Houston. Sixteen percent of nodes were positive for metastases, Dr. Victor G. Prieto said at the 13th World Congress on Cancers of the Skin, which was sponsored by the Skin Cancer Foundation.
Dr. Victor G. Prieto
"The location of a metastatic deposit--subcapsular versus parenchymal--and the size of the largest focus should be reported in the pathology report, in my opinion, when examining sentinel lymph nodes from patients with cutaneous melanoma. We've been doing this for the last 8 years and we think it should be extended to other centers," declared Dr. Prieto, professor of dermatology and director of dermatopathology at M.D. Anderson.
In breast cancer, SLN tumor deposits less than 0.2 mm aren't considered significant by some pathologists. Melanoma is a different matter. There does not seem to be a definite cutoff below which tumor metastasis size doesn't matter. Dr. Prieto has seen cases in which a single melanoma cell detected in the SLN was followed by multiple distant metastases and death within 4 years of skin cancer diagnosis.
"I don't call histologic examination of the sentinel lymph nodes the standard of care in melanoma because that term has medicolegal ramifications. But even though it's not the standard of care, I think a sentinel lymph node examination is very important for our patients. It permits much more accurate staging," Dr. Prieto said.
Ongoing trials should eventually resolve the longstanding controversy as to whether there is any survival benefit to completion lymphadenectomy in patients with positive SLNs. Regardless of how that issue turns out, however, it's clear that staging SLNs provides very important prognostic information.
"We have to remember that a large number of these patients are … between 40 and 50 and they have children and may need to consider setting up college funds and providing for their families," the said.
It is his firm conviction that the entire SLN should be submitted for pathologic evaluation permanently embedded in paraffin rather than in frozen section.
"Even in the best laboratories, the quality of a frozen section is usually below that seen with permanent paraffin-embedded tissue. There's a loss of tissue when specimens are frozen. The subcapsular region, which is the most commonly affected by metastatic melanoma, may be lost," Dr. Prieto said.
Based upon the outcomes of patients with positive SLNs in the M.D. Anderson series, Dr. Prieto and coworkers stratify patients into three prognostic groups. The lowest-risk group is comprised of patients with involvement of one or two SLNs, a largest metastatic nest not more than 2 mm in size, and no ulceration of the primary lesion. Such patients constituted 39% of the SLN-positive population.
Ulceration was present in 43% of the primary melanomas with SLN involvement in this large series. SLN metastases were confined to the subcapsular region in 65% of affected patients.
The intermediate-risk group consisted of patients with ulceration in the primary tumor or any metastatic nest greater than 2 mm in size. The high-risk group, which included 28% of the total SLN-positive group, was made up of patients with involvement of three or more SLNs or ulceration in the primary lesion and any metastatic nest greater than 2 mm.
Ten-year survival was roughly 80% in the low-risk group, 60% in the intermediate-risk cohort, and 30% in the high-risk population.
It can be difficult to detect small numbers of melanoma cells in a SLN without the use of immunohistochemical stains.
At M.D. Anderson, the node is first "breadloafed," which allows evaluation of a relatively large surface area of the subcapsular region, and then the specimen is examined with routine hematoxylin and eosin staining.
If the results are negative, Dr. Prieto and colleagues utilize a cocktail of immunohistochemical stains comprised of HMB45, which is very specific but less than optimally sensitive, coupled with MART1, which is both very specific and more sensitive for melanoma than in HMB45. The flaw with MART1 is it can give false-positive results with macrophages.
If this cocktail proves negative, then and only then do the dermatopathologists resort to S100 protein staining, which is very sensitive but relatively nonspecific.
The Ki67 proliferation marker is employed to distinguish melanoma cells from benign capsular nevi, which should be Ki67-negative.
Dr. Prieto reported no financial conflicts.