A total of 41 sentinel lymph nodes (24 with melanoma and 17 with nevus deposits) were analyzed by FISH (). The corresponding primary melanomas of the melanoma metastases were available for FISH analysis in 18 of the cases. Of these, 14 (78%) showed aberrations by FISH, consistent with the sensitivity of 85% found in previous studies.8
No aberrations were detected in four primaries, one of which was diagnostically challenging and could not unequivocally be diagnosed by histomorphology. The nodal deposits of these cases, two interpreted as nodal nevi and two as melanoma metastasis also did not show any aberrations detectable by FISH (cases 4, 6, 25, and 37)
Comparison of FISH results for the 24 lymph node metastases of melanoma, available corresponding primary tumors and 17 cases of nodal nevus
Of the 24 cases diagnosed as metastatic melanoma by histopathology, 20 (83%) showed aberrations by FISH (), while the remaining four did not. In two of the four negative cases, the nuclear size and nucleoli size of the melanocytes in the lymph node was increased and mitoses and pleomorphism were present, so that there was no doubt that they represented metastatic melanomas that tested falsely negative by FISH (cases 3 and 4); one patient (case 4) developed brain metastases. However, of the two remaining cases upon re-review, case 8 showed more bland appearing melanocytes in the node, raising the possibility that it represented a nodal nevus ().
Case 1, 64 year-old white male with lymph node involvement (a,b) originating from a primary melanoma, 1.0 mm in thickness on the right upper arm (c,d)
Case 8, need to put in description as in 1 and 4
Unfortunately, the primary melanoma of this case could not be obtained for comparison. The presence of clear aberrations in the primary, but none in the lymph node deposit would have supported the notion that the nodal deposit was in fact benign. Case 6, the other lymph node deposit that was FISH negative, also had no aberrations in the primary tumor (). The primary lesion was a nevoid melanoma with a monomorphic population of melanocytes with large sheet-like nests in the superficial dermis with some dispersion and slight maturation with descent (). Deep dermal mitoses within melanocytes were also identified. Neither the primary nor lymph node metastasis showed aberrations, precluding any assessment of clonal relationship between the two lesions that would have helped establish whether the lymph node deposit was in fact benign.
Only one of 17 cases (6%) diagnosed as nodal nevus by histology showed aberrations by FISH (case 30, ). In the positive case, all four parameters were significantly above the threshold, making a false positive FISH result highly unlikely (). The corresponding primary melanoma also showed multiple aberrations, two of which were identical as in the lymph node deposit (11q and 6p gain). This indicates that during the metastatic progression the number of aberrations increased from two to four and that obviously the nodal deposit had been misclassified on morphological grounds (). Interestingly, one case with a primary melanoma had lymph nodes that contained two morphologically different populations of melanocytes; one diagnosed as melanoma and the other as nodal nevus. The primary melanoma and area representing apparent lymph node metastasis morphologically showed a gain in 11q and 6p and a gain in 6p relative to centromere 6. No aberrations were found in the separate focus of nodal nevus (case 23), confirming the histopathological interpretation.
Case 6 need to put in description as in 1 and 4
The histomorphologic analyses of the cases studied is summarized in . Only nodal nevi, not metastases, were found exclusively in the lymph node capsule. The majority of lymph node metastases and all of the nevi demonstrated an epithelioid cellular morphology. By contrast nuclear pleomorphism was more commonly observed in the metastases (63% vs 12%). In contrast to the nodal nevi which had nuclei that were small (less than two times a lymphocyte nucleus) or medium sized (two to three times the size of a lymphocyte), 42% of the metastases demonstrated melanocytes with large nuclear size (at least four times the size of a lymphocyte) and mitoses (50% of cases). Metastases also more frequently showed larger nucleoli (50% vs 18%). Almost half of the 24 metastases showed melanocytic deposits confined to the lymph node parenchyma. The diameter of the lymph nodes deposits was also larger in the metastases ().
Histopathologic features of lymph nodes with metastatic melanoma or nodal nevus
Strong HMB-45 positivity has been repeatedly reported as a helpful criterion in distinguishing melanoma metastasis from nodal nevus.3,5,9–10
HMB-45 immunohistochemistry had been performed on eight of the 24 melanoma metastases at the time of diagnosis, five of which showed strong HMB-45 immunoreactivity, and three were weakly positive. Twelve of the 17 nodal nevi had HMB-45 stain available for review, nine of which were negative and three that were weakly positive.