Histopathologic review of negative sentinel lymph node biopsies in thin melanomas: an argument for the routine use of immunohistochemistry

Abstract

Sentinel lymph node biopsy (SLNB) is performed for some thin melanomas in the presence of concerning histopathological features. There are no defined standards for how sentinel nodes should be processed to detect microscopic metastases. We compared our method of serially sectioning nodes at 2-3 mm intervals and performing one hematoxylin and eosin (H&E) slide versus multiple H&E levels and utilizing immunohistochemistry (IHC). This was a retrospective review of a prospectively collected database identified patients with thin melanomas treated with wide local excision and SLNB between 1995 and 2010. Two patients had positive nodes. Out of 95 patients with negative SLNBs, 48 (49 nodes) patients were evaluable. Additional sections of each SLNB tissue block were stained with H&E (×2), Melan-A (×2) and HMB45 (×2), and reviewed by two pathologists. Additional histopathological sections showed that 1/49 (2.0%) nodes originally called negative had evidence of metastasis, which was evident both on additional H&E levels and by IHC; 3/49 (6.1%) nodes had benign nodal rests. All other nodes (45/49, 91.8%) were negative by H&E and IHC for metastatic disease. This study supports previous work suggesting the value of IHC in detecting micrometastases in melanoma sentinel nodes. Especially for thin melanomas where metastases are uncommon, but where detection of the metastasis upstages considerably from stage IA to IIIA, evaluation of nodes may be enhanced by combining breadloafing at 2-3 mm intervals with multiple H&E sections and IHC analysis.

PRAME expression in 155 cases of metastatic melanoma

“…Melan-A/Mart-1, and/or HMB-45 IHC on all sentinel nodes to maximize sensitivity as well as specificity for malignant cells. [23][24][25] These additional tissue levels examined by IHC also serve a second purpose of increasing the total amount of tissue of each sentinel node that is evaluated by histopathology. However, immunostains chosen for sentinel lymph node evaluation vary in their utility in this setting.…”

“…Although there is no current consensus on sentinel lymph node evaluation for melanoma, many institutions regularly perform S100, Melan‐A/Mart‐1, and/or HMB‐45 IHC on all sentinel nodes to maximize sensitivity as well as specificity for malignant cells 23‐25 . These additional tissue levels examined by IHC also serve a second purpose of increasing the total amount of tissue of each sentinel node that is evaluated by histopathology.…”

Sentinel lymph node assessment in melanoma: current state and future directions

“…Currently, institutional protocol for histopathological handling of sentinel lymph nodes and pathological reporting varies widely. 68,128,129,130,131,132 Macroscopically, two main methods of slicing sentinel lymph nodes exists: 'breadloafing', allowing for better examination of the subcapsular region, and bivalving, allowing for better examination of lymphatic vessels. 130,131 Both the European Organisation for Research and Treatment of Cancer (EORTC) and Sydney Melanoma Unit recommend the utilisation of the bivalving technique in sentinel lymph node histopathological and handling protocol.…”

“…68 The process of IHC staining, which may augment prognostication, is time-consuming and labourintensive. 128,129 IHC has been shown to mildly increase metastatic tumour detection rates in sentinel lymph nodes, but whether these mild increases justify the time and cost of performing IHC is controversial. 129 One study found that, although extensive IHC work-up may increase detection rates, survival is unaffected.…”

“…128,129 IHC has been shown to mildly increase metastatic tumour detection rates in sentinel lymph nodes, but whether these mild increases justify the time and cost of performing IHC is controversial. 129 One study found that, although extensive IHC work-up may increase detection rates, survival is unaffected. 128 Recent work into assessing BRAF V600E expression by IHC in capsular naevi found that, in patients with primary cutaneous melanoma, positive mutation is associated with increased tumour stage and lymph node metastasis, thus showcasing potential added value of IHC staining in SNLB.…”