- Pathologists have traditionally examined lymph nodes obtained from a lymphadenectomy by:
- Examining an H&E-stained section from each paraffin block:
- This conventional approach, however, can miss disease in SLNs:
- Primarily because of sampling error:
- In an MD Anderson study, 8 of 10 patients who underwent SLNB and subsequently developed regional nodal failure in nodal basins that were negative for disease according to conventional histologic examination of SLNs had microscopic disease detected when the SLNs were reassessed using specialized pathologic techniques
- Data from this and other studies suggest that failure to use specialized techniques, rather than failure to correctly identify SLNs, accounts for many cases of false-negative findings on SLNB
- These studies helped to define the current standards of SLN assessment using more enhanced pathologic evaluation than had been previously performed
- Primarily because of sampling error:
- This conventional approach, however, can miss disease in SLNs:
- Examining an H&E-stained section from each paraffin block:
- With the SLNB technique, fewer lymph nodes are submitted for analysis than are submitted with formal lymphadenectomy, and the pathologist can therefore focus on only those nodes that are at the highest risk
- Currently, the combination of H&E assessment of several levels (i.e., serial sectioning) and immunohistochemical analysis is generally considered a standard practice in assessing SLNs
- Several antibodies directed against melanoma-associated antigens:
- S-100, HMB-45, tyrosinase, MAGE3, and MART-1:
- Are routinely used for immunohistochemical evaluation
- Because certain antibodies have low specificity (S-100) and others have low sensitivity (HMB-45, MAGE3, and tyrosinase):
- A panel of antibodies is commonly used
- S-100, HMB-45, tyrosinase, MAGE3, and MART-1:
- At MD Anderson Cancer Center:
- There panel includes an antimelanocytic cocktail:
- HMB45, anti-MART1 and anti-tyrosinase
- There panel includes an antimelanocytic cocktail:
- The use of frozen section for immediate evaluation of SLNs has been controversial in melanoma:
- Frozen sections usually provide suboptimal morphology and may lack the subcapsular region of the lymph node:
- An area likely involved in SLN metastases
- Also, processing of the frozen tissue requires additional sectioning:
- Micrometastases may be lost in the discarded unexamined sections
- I feel strongly that the use of frozen section risks a lower accuracy of detection of SLN metastases
- Historically this approach was employed for the rare clinical scenario if a grossly suspicious SLN was identified and if a formal preoperative discussion of possible concomitant CLND was considered:
- Given the infrequent use of CLND following results of the Multicenter Selective Lymphadenectomy Trial-II (MSLT-II) trial:
- This approach has been further rendered obsolete
- Given the infrequent use of CLND following results of the Multicenter Selective Lymphadenectomy Trial-II (MSLT-II) trial:
- Frozen sections usually provide suboptimal morphology and may lack the subcapsular region of the lymph node:
- Purpose:
- To detect micrometastatic disease in regional lymph nodes
- Guides prognosis, staging (AJCC), and eligibility for adjuvant therapy
- Gross Examination:
- SLNs are bisected or serially sectioned at 1 to 2 mm intervals perpendicular to the long axis:
- All tissue is submitted for histologic evaluation
- Reference:
- College of American Pathologists (CAP) Protocol for Melanoma (2023 Update)
- SLNs are bisected or serially sectioned at 1 to 2 mm intervals perpendicular to the long axis:
- Histologic Evaluation:
- Hematoxylin and eosin (H&E) staining is the standard initial method
- Immunohistochemistry (IHC) is used when H&E is equivocal
- IHC Markers:
- S100: Very sensitive, but not specific
- Melan-A (MART-1) and HMB-45:
- More specific for melanocytic lineage
- Reference:
- Cochran AJ, Wen DR, Morton DL. Cancer. 1999;85(5):1228–1238.
- Reporting Parameters:
- Pathologic reports should include:
- Number of SLNs examined
- Number of SLNs positive for metastasis
- Size of the largest tumor deposit (tumor burden)
- Presence of extracapsular extension
- Location of metastasis:
- Subcapsular, parenchymal, or multifocal
- Mitotic activity, if assessable
- Reference:
- Gershenwald JE, Scolyer RA, Hess KR, et al. CA Cancer J Clin. 2017;67(6):472–492.
CAP Cancer Protocol: Melanoma of Skin (2023)
- Gershenwald JE, Scolyer RA, Hess KR, et al. CA Cancer J Clin. 2017;67(6):472–492.
- Pathologic reports should include:
- Tumor Burden Stratification:
- Micrometastases (< 0.1 mm):
- Often associated with excellent prognosis
- Deposits ≥ 1 mm:
- Significantly higher risk of recurrence and worse melanoma-specific survival
- Reference:
- van der Ploeg AP, van Akkooi AC, et al. Ann Surg Oncol. 2011;18(2):519–528.
- Micrometastases (< 0.1 mm):
- Ultrastaging (Optional / Selective):
- Serial sectioning and multiple IHC stains:
- May increase detection of minimal disease but has limited proven prognostic value beyond standard pathology
- Not uniformly recommended due to low clinical significance of isolated tumor cells (ITCs)
- Serial sectioning and multiple IHC stains:
- Nodal Staging (AJCC 8th Edition):
- SLN involvement determines Stage III subcategorization:
- IIIA:
- Micrometastases, no ulceration
- IIIB to IIIC:
- Larger burden, ulcerated primary, or multiple nodes
- IIIA:
- SLN involvement determines Stage III subcategorization:
- Clinical Implications:
- SLN positivity leads to consideration of adjuvant immunotherapy or targeted therapy
- Completion lymph node dissection (CLND) is no longer routine per MSLT-II
Rodrigo Arrangoiz MS, MD, FACS, FSSO 