Subcutaneous panniculitis-like T-cell lymphoma (ORPHA:86884)
A rare cytotoxic cutaneous alpha-beta T-cell lymphoma characterized by solitary or multiple erythematous subcutaneous nodules and plaques that can be localized to the lower extremities or generalized. It has been recognized as a distinct subset of peripheral T-cell lymphomas originating and presenting primarily in the subcutaneous fat tissue and often associated with hemophagocytic lymphohistiocytosis.
Epidemiology
The exact incidence is unknown but estimated around 1/10,000,000 individuals per year in Europe. A slight female preponderance has been reported. Median age of diagnosis is around 40 years old, but cases are reported from 1 to 90 years old.
Clinical description
Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is characterized by solitary or multiple erythematous subcutaneous nodules and plaques (proliferation of T lymphocytes and macrophages in the subcutaneous fat lobule), which appear in crops and are localized to the lower extremities or may be more generalized. Systemic manifestations include fever, chills, malaise, weight loss, hepatosplenomegaly, mucosal ulcers, and serosal effusions. SPTCL may be accompanied by hemophagocytic syndrome (characterized by the proliferation of histiocytes and phagocytosis of blood elements, hepatosplenomegaly, and coagulopathy and reported in approximately 30-40% of cases), which may be fatal.
Etiology
The etiology is not completely understood. An infectious trigger events has been described in some pediatric cases. Recently, germline homozygous mutation of HAVCR2 has been associated with SPTCL in 32 to 85% of patients.
Diagnostic methods
Repeated biopsies may be required to establish the diagnosis. Pathology is characterized by CD8+ T cells expressing alpha-beta T cell antigen receptors (TCRs) and infiltrating subcutaneous adipose tissue, rimming adipocytes in a lace-like pattern, and adipocyte necrosis. The immunophenotype of the lymphoma is CD8+, CD56-, CD30-, granzymeB+, TiA-1, betaF1+. Molecular clonality assay should exclude gamma-delta T cell lymphoma which has a more aggressive course and is considered as a distinct entity.
Differential diagnosis
The differential diagnosis includes other lymphomas as well as atypical lobular panniculitis and cytophagic histiocytic panniculitis. Lupus panniculitis can be excluded by the frequent MxA staining on lymphocytes, macrophages and on clusters of CD123+CD303+ PDC, and by the presence of lymphoid follicles and B cells.
Genetic counseling
Transmission of HAVCR2-associated risk is autosomal recessive with incomplete penetrance. Genetic counseling should be offered to at-risk couples (both individuals are carriers of a disease-causing mutation) informing them that there is a 25% risk of having a child with heterozygous HAVCR2 variant at each pregnancy.
Management and treatment
SPTCL may be rapidly fatal or indolent. Most patients respond to immunosuppressive drugs (ciclosporin A, corticosteroids, hydroxychloroquine or methotrexate). Systemic chemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisone) is an available option in severe case or when associated with hemophagocytic lymphohistiocytosis. Allogeneic hematopoietic stem cell transplantation has been proposed in severe cases and is a curative treatment option, especially in HAVCR2-variant cases.
Prognosis
SPTCL is a life-threatening disease with a good prognosis in most cases. 2-years overall survival is estimated around 90% and complete remission around 80% with immunosuppressive drugs.

                            Last update: 
                            April 2024


                            - Expert reviewer(s): 
                            Pr David MICHONNEAU