Controversies and considerations in the diagnosis of primary cutaneous CD4⁺ small/medium T-cell lymphoma

Primary cutaneous CD4⁺ small/medium T-cell lymphoma is a provisional and controversial entity with a broad differential diagnosis. Despite being an uncommon lymphoma, it is a frequent diagnostic consideration in cutaneous biopsies with a dense lymphoid infiltrate because it shows overlapping features with reactive lymphoid hyperplasia (pseudolymphoma) and a variety of other primary cutaneous and systemic lymphomas. However, proper classification of this process is important for determining patient prognosis and treatment options.

To review the clinical, morphologic, immunophenotypic, and genetic features of primary cutaneous CD4⁺ small/medium T-cell lymphoma and contrast those features with entities in the differential diagnosis.

Applicable literature will be reviewed with emphasis on current controversies and distinguishing characteristics.

Although many consider primary cutaneous CD4⁺ small/medium T-cell lymphoma to be indistinguishable from reactive lymphoid hyperplasia/pseudolymphoma, it can be differentiated from other primary cutaneous and systemic lymphomas. Patients with solitary lesions of primary cutaneous CD4⁺ small/medium T-cell lymphoma generally have an excellent prognosis. Nevertheless, a subset of patients who have been reported to meet criteria for this lymphoma have followed a more-aggressive course; however, those patients show some differing clinical, morphologic, and immunophenotypic features.