Andre Meier

Prognostic significance of isolated HMB45 or melan a positive cells in melanoma sentinel lymph nodes

The detection of micrometastases (defined as groups of malignant cells) in the sentinel lymph node (SLN) is an important prognostic tool in melanoma. The use of immunohistochemistry with melanocytic markers such as HMB45 and Melan A increases the detection rate of micrometastases but there are also cases with isolated immunohistochemically positive cells (IPC). To determine the prognostic significance of isolated HMB45 and/or Melan A positive cells in melanoma SLN, we compared the clinical course of 47 patients with IPC to 308 patients with negative SLN and to 122 patients with micrometastases. The mean follow-up was 38.1 months. By Kaplan-Meier analyses, relapse free survival and overall survival of patients with IPC were similar to SLN negative patients, whereas patients with micrometastases had a significantly worse relapse free survival and overall survival. In the 47 patients with IPC, 6 relapses (12.8%) and 3 melanoma-related death (6.4%) occurred, in the SLN negative patients 36 relapses (11.7%) and 17 melanoma-related deaths (5.5%), in the patients with micrometastases 46 relapses (37.7%) and 29 melanoma-related deaths (23.8%). Prognosis of patients with IPC in SLN did not correlate with type of positive staining (HMB45, Melan A, or both), capsular involvement, number of cells, presence of cytologic atypias of IPC, or tumor penetrative depth. In conclusion, with short-term follow-up IPC in melanoma SLN are without prognostic significance.

Autoimmunity as a prognostic factor in melanoma patients treated with adjuvant low-dose interferon alpha.

Interferon alpha is used for the adjuvant treatment of malignant melanoma at different dosages (high‐, intermediate‐, low‐dose therapy). Only a minority of patients might benefit from this therapy, and markers to identify such patients are missing. A recent study suggested that melanoma patients developing autoantibodies or clinical manifestations of autoimmunity during adjuvant high‐dose interferon alpha treatment had a significant survival benefit. We retrospectively reviewed 134 melanoma patients from our institution treated with adjuvant low‐dose interferon alpha therapy and correlated the development of autoimmune diseases with prognosis. Interferon (IFN) therapy was routinely monitored by history, physical examination and laboratory tests before, after the first month and then after every 3 months of therapy. During a median follow up of 46.0 months (8.5–79.0 months) 28 patients (20.9%) suffered from recurrences and melanoma related deaths occurred in 16 patients (11.9%). In 20 patients (14.9%) autoimmune thyroiditis (AIT) was diagnosed during IFN therapy, one of these 20 patients developed rheumatoid arthritis later while continuing IFN therapy. Other autoimmune diseases were not observed. In 2 patients (one with AIT and one with arthritis) the autoimmune disease led to discontinuation of IFN therapy, in the other patients AIT remained subclinical or responded well to treatment while IFN therapy was continued. Kaplan–Meier analyses revealed a significant better recurrence free survival and a trend for a better overall survival for patients with AIT. Thus, autoimmunity triggered by low‐dose IFN therapy appears to indicate an improved prognosis and should encourage continuation of IFN therapy.

Comparison of classification systems in melanoma sentinel lymph nodes--an analysis of 697 patients from a single center.

In melanoma, different classification systems have been proposed that predict overall survival (OS) and recurrence‐free survival (RFS) based on findings in the sentinel lymph node (SLN). The authors of this report compared the RFS and OS of 697 melanoma patients as predicted by various classification systems.

Is there a therapeutic benefit of complete lymph node dissection in melanoma patients with low tumor burden in the sentinel node

In the case of a positive sentinel lymph node (SLN), melanoma patients are recommended to proceed to complete lymph node dissection (CLND). However, CLND for SLN-positive patients – especially with minimal tumor burden in SLN – is becoming more controversial. We analyzed the clinical course of 305 SLN-positive patients with a mean follow-up of 51.1 months by Kaplan–Meier analyses. Overall, 58/305 (17%) patients did not undergo CLND. These were compared with a matched selection of 58 comparable patients who underwent CLND. Moreover, 106/305 patients with minimal tumor burden in SLN (<0.1 mm diameter of the largest tumor deposit) were analyzed separately. Of these 106 patients, 34 did not undergo CLND, whereas 72/106 patients were treated by CLND. In the matched groups, the CLND group and the non-CLND group did not differ significantly with respect to clinical characteristics, characteristics of the primary melanoma, and histopathological parameters of SLN. There were no differences in recurrence-free survival (P=0.765) and overall survival (P=0.844). The total number of regional lymph node metastases and time to regional lymph node metastases were not significantly higher for non-CLND patients. The subgroup of patients with minimal tumor burden in SLN also did not benefit significantly from CLND. In our analyses from a single German center, we could not find any evidence for a therapeutic survival benefit for CLND after positive SLN. However, future prospective randomized trials should confirm these data.

Reply to assessment of capsular melanoma cell deposits in sentinel lymph nodes

With great interest we read the article by Meier et al., who reported on a scoring system used for risk assessment based on tumor load within the sentinel lymph node (SLN) of patients with cutaneous melanoma. The authors take into consideration 3 prognostic parameters: 1) the tumor penetrative depth (TPD) according to Starz, 2) the greatest dimension of the largest tumor cell deposit, and 3) capsular involvement, ie, the presence of tumor cells within the capsule of the SLN. In our opinion, the term ‘‘capsular involvement’’ needs clarification because it includes separate forms: 1) pericapsular or intracapsular lymphangiosis, ie, tumor cells in the lumen of lymph vessels penetrating the nodal capsule; 2) very infrequently, the presence of small groups of tumor cells situated in the vicinity of capsular lymph vessels, which can hardly be distinguished from nevus cells or from lymphangiosis; 3) capsular invasion, ie, partial or complete capsular destruction as a result of the expansion of intranodal melanoma metastasis, finally resulting in 4) capsular breakthrough, ie, further spread in the perinodal tissue. With respect to the assessment of capsular deposits of melanoma cells, only a fair reproducibility even between experienced pathologists was reported. We applied the Kaplan-Meier estimate to our collective of 190 SLN-positive patients. Capsular invasion was observed in 19 patients. Of those, 7 had capsular breakthrough. Capsular invasion was confirmed to be a significant prognostic factor (P 1⁄4 .02). Of our SLN-positive patients, 71 (37%) had lymphangiosis; 7 of them had no further lymphatic metastasis. The presence of lymphangiosis did not significantly influence recurrence-free or overall survival. Based on our observation, we have concluded that further studies are needed to clarify the prognostic impact of intracapsular lymphangiosis melanomatosa.

Evaluation of criteria in sentinel nodes of melanoma patients that predict involvement of non-sentinel nodes

Purpose of the Study Previous studies described various criteria in sentinel lymph nodes (SLNs) of melanoma patients that predict the involvement of further, nonsentinel lymph nodes (NSLNs). Such criteria should facilitate the selection of patients who might benefit from a completion lymphadenectomy. These preceding studies found different criteria using individual groups of patients, and it is currently unclear which parameters are most important.