Lymphocytic Infiltration in Melanoma: Limited Clinical Significance
The presence of tumor-infiltrating lymphocytes (TILs) in melanoma has unclear prognostic value and is no longer recommended for routine pathology reporting due to concerns about reproducibility and lack of independent prognostic significance. 1
Current Guideline Recommendations
NCCN Guidelines Position (2021)
The NCCN panel explicitly removed tumor-infiltrating lymphocytes from the list of features encouraged for reporting in version 1.2021, despite TILs remaining a core element in some pathology protocols. 1 This decision was based on:
- Concerns about reproducibility between pathologists 1
- Lack of independent prognostic value for recurrence-free survival or overall survival 1
- Most studies finding TILs are not an independent prognostic factor 1
UK Guidelines Position (2010)
The British Association of Dermatologists states that it remains unclear whether tumor-infiltrating lymphocytes have prognostic value. 1 The traditional classification system (absent, non-brisk, brisk) is subject to wide observer variation, making it unreliable for clinical decision-making. 1
Classification System Issues
When TILs are reported, the categories are defined as: 1
- Absent: No lymphocytes infiltrating among tumor cells (but does not exclude lymphocytes in surrounding dermis)
- Non-brisk: Patchy or discontinuous infiltrate either among peripheral cells or in tumor center
- Brisk: Continuous infiltrate, may be confined to peripheral cells
These categories are further qualified by intensity (mild, moderate, severe), but this adds another layer of subjective interpretation. 1
Research Evidence Context
While some research suggests potential prognostic significance: 2, 3, 4
- One study in thick (T4) melanomas showed TIL presence correlated with improved survival in multivariate analysis 4
- TILs may reflect ongoing host-tumor immunologic interaction 3
However, these research findings have not translated into guideline recommendations because the evidence is inconsistent and the assessment methodology lacks standardization. 1
Therapeutic Context: TIL Cell Therapy
The therapeutic use of TILs is entirely separate from their prognostic assessment in primary tumors: 1
- TIL cell therapy involves surgical resection, ex vivo expansion, and reinfusion of tumor-infiltrating lymphocytes
- FDA-approved lifileucel showed 31.4% objective response rate in heavily pretreated metastatic melanoma 1
- This therapeutic application does not validate TILs as a prognostic marker in primary tumor pathology
Clinical Bottom Line
Do not rely on TIL assessment for prognostic stratification or treatment decisions. 1 Instead, focus on established prognostic factors: 1, 5, 6
- Breslow thickness (most important for localized disease) 5, 6
- Ulceration status 5, 6
- Mitotic count 1
- Sentinel lymph node status (most important prognostic factor when performed) 5
- Number of involved lymph nodes (for regional disease) 5, 6
What Should Be Reported Instead
Pathology reports should prioritize: 1
- Breslow thickness
- Ulceration presence/absence
- Mitotic count
- Margins of excision
- Lymphovascular invasion (when present)
- Microsatellites (upstages to N1c-N3c) 1