Sentinel lymph nodes containing very small (<0.1 mm) deposits of metastatic melanoma cannot be safely regarded as tumor-negative

Abstract

Background: Some authors have suggested that patients with very small (<0.1 mm) deposits of metastatic melanoma in sentinel lymph nodes (SLNs) should be considered SLN-negative, whereas others have reported that such patients can have adverse long-term outcomes. The aims of the present study were to determine whether extensive sectioning of SLNs resulted in more accurate categorization of histologic features of tumor deposits and to assess prognostic associations of histologic parameters obtained using more intensive sectioning protocols.

Methods: From patients with a single primary cutaneous melanoma who underwent SLN biopsy between 1991 and 2008, those in which the maximum size of the largest tumor deposit (MaxSize) in SLNs was <0.1 mm in the original sections were identified. Five batches of additional sections were cut from the SLN tissue blocks at intervals of 250 μm. The 1st batch was cut from the blocks without any trimming; these sections were therefore immediately adjacent to the original sections. Each batch included 5 sequential sections, the 1st and 5th stained with hematoxylin-eosin, and the 2nd, 3rd, and 4th stained immunohistochemically with S-100, HMB-45, and Melan-A, respectively. In each batch of sections, the following histologic features of tumor deposit(s) in the SLNs were evaluated: MaxSize; tumor penetrative depth (TPD) (defined as the maximum depth of tumor deposit(s) from the inner margin of the lymph node capsule), and intranodal location (classified as subcapsular if the tumor deposit(s) were confined to the subcapsular zone or parenchymal if there was any involvement of the nodal parenchyma beyond the subcapsular zone). The measured histologic parameters were compared in each batch of sections. The association of histologic parameters with overall survival was assessed for the parameters measured in each batch of sections.

Results: There were 20 eligible patients (15 females, 5 males, median age 60 years). After a median follow-up duration of 40 months, 4 patients had died from melanoma and 2 patients of unknown causes. Completion lymph node dissection (CLND) was performed in 13 cases (65%) and was negative in all cases. Relative to the measured values on the original sections, all 3 parameters were upstaged in subsequent batches of sections, but no further upstaging of MaxSize, TPD, or location was seen beyond batch 3, batch 4, and batch 2, respectively. Increasing MaxSize was associated with significantly poorer overall survival in batches 1, 2, and 3. Parenchymal involvement was significantly associated with poorer survival in batches 2-5. TPD was not significantly associated with overall survival.

Conclusions: The results of this study indicate that very small (<0.1 mm) deposits of melanoma in SLNs may be associated with adverse clinical outcomes and that this is due, at least in part, to the underestimation of SLN tumor burden in the initial sections. Our evidence does not support clinical decision-making on the assumption that patients with very small melanoma deposits in SLNs have the same outcome as those who are SLN-negative.