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- Presentation
Diagnostic Tools and Pitfalls in Cutaneous T-Cell Lymphoma
Description
The talk reviewed diagnostic tools for cutaneous T-cell lymphoma (CTCL), especially mycosis fungoides, and emphasized how easily early or subtle disease can be mistaken for inflammatory or reactive dermatoses. Histopathology remains central, but biopsy findings can be minimal or variable even within the same patient. Immunohistochemistry can help, with MF often showing CD3+/CD4+/CD8- cells and sometimes loss of CD2, CD5, or CD7, but normal ratios or atypical phenotypes do not exclude disease. T-cell receptor (TCR) clonality testing is useful but imperfect: a clone supports a neoplastic process only when it is reproducible across sites and correlates with clinical and microscopic findings, since clones can also appear in benign inflammation. Next-generation sequencing is more sensitive than older methods and can estimate clone burden, but low-level clonality is a major pitfall. The speaker also discussed gamma-delta versus alpha-beta phenotypes, and TRBC1 as an adjunct marker for clonality that can be helpful but does not replace TCR studies. Case examples highlighted misleading scenarios, including dupilumab-associated spongiotic/lymphoid reactions that mimicked CTCL, lymphomatoid papulosis with an incidental blood clone, and a lesion initially suspected to be lymphoma that was ultimately leishmaniasis. The key take-home points were to correlate pathology with clinical context, be cautious with low-level clonality and blood clones, and avoid diagnosing CTCL based on lymphocytes alone.
View moreConclusions
- Cutaneous T-cell lymphoma, especially early mycosis fungoides, can be subtle histologically and often requires correlation with the clinical picture rather than relying on a single biopsy or stain.
- Immunohistochemistry is useful but imperfect because CD4 predominance and loss of markers such as CD7 support MF only when interpreted in context, and normal or atypical patterns do not exclude disease.
- T-cell receptor clonality testing is supportive rather than diagnostic, because clonal populations can occur in inflammatory dermatoses and other non-CTCL conditions.
- Next-generation sequencing is more informative than older PCR-based methods for TCR analysis, but low-level clones and technical issues can still mislead interpretation.
- Repeated or reproducible clonality across multiple sites is more convincing for a true neoplastic process than an isolated low-level clone.
- TRBC1 immunohistochemistry can help identify alpha-beta T-cell clonality, but it is an adjunct rather than a replacement for TCR studies and is not useful for gamma-delta T cells.
- Peripheral blood flow cytometry and blood clonality are only meaningful for CTCL when they match the skin clone; otherwise they may represent incidental or reactive T-cell clones.
- T-cell clones of uncertain significance are common in healthy people and can resemble malignant findings, so blood clones alone should not trigger a CTCL diagnosis.
- Low-level blood or skin clonality, especially at or below about 5%, should be interpreted cautiously because it may be misleading or incidental.
- Several CTCL mimickers, including spongiotic dermatitis, dupilumab-associated lymphoid reactions, lymphomatoid papulosis, and infection such as leishmaniasis, can look suspicious for lymphoma but follow a different course.
- The overall message is that CTCL diagnosis should be made by integrating histology, immunophenotype, molecular data, blood studies, and clinical evolution rather than by any single laboratory result.
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