A solitary clonal T-cell infiltrate on the thigh
A 44-year-old woman has a solitary 3-cm violaceous, indurated plaque on the left thigh that has persisted for 8 months. She has no other skin lesions, no lymphadenopathy, and no B symptoms; blood counts and LDH are normal. A 4-mm punch biopsy shows a dense band-like lymphocytic infiltrate in the upper dermis with marked epidermotropism, scattered cells with hyperchromatic, cerebriform nuclei, and small collections of atypical cells within the epidermis; there is no spongiosis and only focal interface change. Immunohistochemistry shows CD3-positive, CD4-predominant cells with partial loss of CD7, scattered CD8 cells, CD30 negativity, CD56 negativity, and EBER negativity. TCR beta gene rearrangement studies show a clonal peak. The patient has well-controlled hypothyroidism and takes levothyroxine only.
1. How much weight should the clonal TCR result carry, and what clinical or laboratory information would make it more or less meaningful?
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A clonal TCR result is supportive but not diagnostic. Identical clones can be found in benign inflammatory dermatoses, particularly pityriasis lichenoides, lichen planus, and some drug eruptions, and occasionally in T-cell pseudolymphomas. Specificity rises when:
- The same clone is present in multiple lesions or in blood.
- The clone is dominant and reproducible on repeat testing.
- It is accompanied by a matching immunophenotype (CD4 predominance, loss of pan-T markers) and convincing epidermotropism.
Specificity falls when:
- The infiltrate is mixed with B cells, plasma cells, and eosinophils, or shows germinal centers.
- The clinical lesion is solitary and resolves.
- The clone is small and lost on repeat testing.
The BIOMED-2 protocol improves sensitivity, but a polyclonal result does not exclude mycosis fungoides, especially early or treated disease. The result must be interpreted alongside the H&E and the clinical picture, not as a standalone test.
2. Which histologic and immunophenotypic features in this biopsy support mycosis fungoides, and which features argue against it?
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Supports mycosis fungoides:
- Epidermotropism without spongiosis, with lymphocytes aligned along the junction and small intraepidermal collections.
- Cerebriform nuclei and a CD4-predominant T-cell infiltrate with partial loss of CD7.
- A band-like upper dermal infiltrate with wiry collagen.
Argues against mycosis fungoides or favors an inflammatory mimic:
- A solitary lesion; mycosis fungoides is usually multifocal, although solitary lesions occur.
- Prominent plasma cells or eosinophils, which are unusual in mycosis fungoides.
- Preservation of CD7 and a mixed CD4/CD8 population.
- A clear trigger or drug history.
Partial loss of CD7 is supportive but not specific; CD7 can be lost in benign inflammation. CD26 loss and an altered CD4 to CD8 ratio add support. Overall, the morphologic and immunophenotypic findings are compatible with mycosis fungoides but not conclusive on one biopsy.
3. What is your next step, and what would you avoid doing?
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Next steps:
- Full skin examination, photography, and documentation of any other lesions.
- Staging with blood TCR gene rearrangement and LDH; imaging only if there is lymphadenopathy or advanced disease, since a solitary plaque does not automatically require PET-CT.
- Repeat biopsy of the same lesion or a new lesion after a period of observation, with review by a hematopathologist.
- Consider skin-directed therapy with close follow-up rather than systemic therapy.
What I would avoid:
- Diagnosing T-cell lymphoma on the basis of clonality alone and starting systemic chemotherapy.
- Empirical systemic corticosteroids before the diagnosis is settled, because they can mask progression.
- Reassuring the patient that the lesion is definitely benign without follow-up.
If the lesion persists or new lesions appear, the diagnosis of mycosis fungoides becomes much more likely, and skin-directed therapy such as topical corticosteroids, nitrogen mustard, or phototherapy would be appropriate.