Subcutaneous panniculitis-like T-cell lymphoma

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare type of lymphoma with an atypical T-lymphocyte infiltrate in subcutaneous fat. This typically presents clinically as tender nodules or plaques, mimicking inflammatory panniculitis.

Some cases are associated with homozygous constitutional (germline) pathogenic variants in HAVCR2, which have higher risk of developing hemophagocytic lymphohistiocytosis (HLH).

Patients with SPTCL typically present with:

• skin lesions: multiple, tender and sometimes erythematous nodules or plaques, predominantly over the extremities or trunk (on resolution, lipoatrophy can be present); and
• systemic features: fevers, weight loss and fatigue can co-present with skin findings (HLH presents in a minority of cases, with a worse prognosis associated).

SPTCL can follow an initially indolent course, mimicking inflammatory panniculitis before manifesting as SPTCL.

Constitutional (germline) homozygous or compound heterozygous pathogenic variants in HAVCR2 have been found in over half of cases of SPTCL. These patients carry a higher risk of developing HLH.

SPTCL can be difficult to diagnose, with histopathological features similar to lobular panniculitides.

• Deep incisional biopsy: A full-thickness skin biopsy that includes subcutaneous fat is key for evaluation.
• Immunohistochemistry: The neoplastic cells are usually:
• • CD3 positive;
• • CD8 positive; and/or
• • negative for CD4 and, often, other markers that help to rule out alternative diagnoses.
• Molecular analysis: This takes the form of monoclonal T-cell receptor rearrangement.
• Genomic testing: Confirming a constitutional (germline) homozygous or compound heterozygous HAVCR2 pathogenic variant can increase diagnostic likelihood of SPTCL.

The majority of constitutional (germline) pathogenic variants in HAVCR2 are homozygous loss-of-function missense variants. The penetrance of such variants is not currently well defined. Parental analysis may be informative in determining other at-risk members in the family. Onset can often be in childhood, supporting testing of children who may be at risk.

Treatment of SPTCL is tailored to the disease subtype and the clinical severity. Options include immunosuppressive therapy and chemotherapy. Ruxolitinib has been used in cases of HAVCR2-related HLH. Treatment plans should be individualised, taking into account the patient’s overall health, disease extent and immunophenotypic characteristics.

For clinicians

• NHS England: National Genomic Test Directory

References:

• Gayden T, Sepulveda FE, Dong-Anh K-Q and others. ‘Germline HAVCR2 mutations altering TIM-3 characterize subcutaneous panniculitis-like T cell lymphomas with hemophagocytic lymphohistiocytic syndrome‘. Nature Genetics 2018: volume 50, pages 1,650–1,657. DOI: 10.1038/s41588-018-0251-4

For patients

• My Lymphoma Team: Subcutaneous panniculitis-like T-cell lymphoma