Subcutaneous panniculitis-like t-cell lymphoma C84.5

Gonzales 1991

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare form of "T-cell non-Hodgkin's lymphoma" in which CD8+ cytotoxic T cells infiltrate adipose tissue and form inflammatory subcutaneous plaques or nodules.

In the familial forms of subcutaneous panniculitis-like T-cell lymphoma reported by Gayden et al (2018), autosomal recessive mutations in the HAVCR2 gene were causative.

Both children and adults can be affected, with an average age at diagnosis of 36 years and a predominance of the female gender.

especially the lower extremity.

Onset with a clinical picture "reminiscent of an infection" with a pronounced general feeling of illness, fever, weight loss.

The skin findings are atypical for cutaneous T-cell lymphoma. There are usually asymptomatic or slightly painful, subcutaneous, red (inflammatory), plate-like or nodular indurations measuring 5.0-20.0 cm in diameter, so that the first clinical impression is more reminiscent of erythema nodosum or atypically localized erythema induratum. Long-term relapsing courses with spontaneous remissions are the rule. Ulcerations are the exception (in about 6% of patients).

If a hemophagocytosis syndrome is detected (in about 17% of patients), the prognostically unfavorable subcutaneous form of systemic gamma/delta T-cell lymphoma must be considered. In this case, sepsis-like clinical pictures may develop.

Dense, nodular infiltrate in the subcutis, with very pleomorphic lymphoid cells of different sizes, which often accumulate in a ring around lipocytes (so-called rimming). General view as in lobular panniculitis. Angiocentric growth pattern with fat tissue necroses. Granulomatous secondary reaction, erythrophagocytosis in 30% of cases.

Immunohistology: Tumor cells express T-cell markers: CD3, CD8, CD43, CD45RO, CD4 is not expressed! Tumor cells express cytotoxic proteins such as Perforin, TIA-1 and Granzym.

Clonal rearragenment of TZR genes can be detected in most cases.

Immunocytogenetic. Expression of the alpha/beta T cell receptor (TZR). Expression of the beta/gamma chain of the T cell receptor indicates subcutaneous infiltration of the systemic form of gamma/delta T cell lymphoma (GD-TZL) with poor prognosis.

Clinical:

• Panniculitis: Mostly subacute, mostly painful nodular subcutaneous infiltrates.
• Profound circumscribed scleroderma: Slow, non painful, firm indurations. Histology is diagnostic.

Histological:

• Subcutaneous form of gamma/delta T-cell lymphoma: expression of the gamma/delta chain of TZR. Important DD(!) because systemic gamma/delta T-cell lymphoma has a significantly worse prognosis.
• Lupus panniculitis: infiltration by small lymphocytes, no cell atypia.
• Extranodal NK/T-cell lymphoma: expression of CD56; association with EBV.

In 16 patients with SPTCL, Gayden et al (2018) found that immunosuppressive and chemotherapeutic treatment was effective, but some patients achieved complete remission only after hematopoietic stem cell transplantation. One patient treated with anakinra, an IL1 inhibitor, experienced disappearance of symptoms and sustained improvement in general condition.

In individual foci, radiation therapy with fast elecrodes should be considered.

Mostly slow progressive course. 5-year survival rate of 80%.

The 48-year-old patient reported a changeable clinical picture on both legs for 4-5 years with little painful, plate-like indurations, which regressed leaving deeply retracted, also extensive "scarring" of skin and subcutis. For 1 year analogous changes also occurred in the lower abdomen.

The patient's general condition was unremarkable.

Laboratory: blood and differential blood counts were unremarkable. Liver enzymes, lipase, amylase, alpha-1-antitrypsin, kidney values o.B. No pathological immune parameters. Borrelia serology unremarkable.

Imaging procedures: o.B.

Histopathological and molecular biological findings: Dense nodular infiltrate in the subcutis, with very pleomorphic lymphoid cells of different sizes, often accumulating in a ring around lipocytes (so-called rimming). Overview picture as in lobular panniculitis. Immunohistology: Tumor cells express T cell markers: CD3, CD8, CD43, CD45RO, not expressed is CD4! Clonal rearragenment of TZR genes was detectable.

Ther: Initiation of steroidal monotherapy (prednisolone 1mg/kg/KG i.v.). Complete regression of indurations after 8 weeks. Maintenance dose 5mg/p.o. After 6 months local recurrence. Now radiotherapy (GD 36 Gy, fractionation 5 x /week 2,0Gy). Under this complete regression and 2 years free of recurrence.

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Gayden et al (2018) reported 16 patients, including 2 sibling pairs, with SPTCL. Twelve patients were of East Asian origin, including Polynesian, three were of Caucasian and European origin, and one was of North African descent. Most patients presented in the first or second decade of life (usually late childhood) with various symptoms of inflammatory disease, including fever, facial swelling, fatigue, painful flanks, pancytopenia or anemia, and subcutaneous nodules suggestive of panniculitis. However, several patients presented as adults. Skin biopsies confirmed panniculitis with cytotoxic CD8+ T-cell infiltrations with adipocyte rims and necrosis, consistent with a diagnosis of SPTCL. Molecular studies of the skin lesions, when performed, showed T-cell receptor-beta chain rearrangements that were monoclonal in most cases.

Bone marrow examination revealed hemophagocytic lymphohistiocytosis (HLH) in 14 of 16 patients and often showed adipocyte infiltration by CD8+ T cells.

Laboratory findings in 1 patient (P4) showed signs of inflammation with elevated serum levels of inflammatory cytokines during active disease. Patient-derived T cells and macrophages produced elevated levels of inflammatory cytokines in vitro, including TNFA, IL2, and IL1B. Other variable laboratory findings included abnormal liver enzymes, autoantibodies, and features associated with hemophagocytic lymphohistiocytosis, such as elevated triglycerides, hyperferritinemia, and hypofibrinogenemia.

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Polprasert et al (2019) reported 11 unrelated patients of East Asian descent with SPTCL. The median age at diagnosis was 32 years (range, 5 to 59). Multiple SPTCL lesions were commonly observed on the trunk, eyelids, extremities, and buccal mucosa. Pathologic analysis revealed atypical CD8+ cytotoxic T cells infiltrating the subcutaneous adipose tissue and lining the adipocytes. 2 of the 11 patients developed hemophagocytic lymphohistiocytosis. Most patients had a monoclonal T-cell receptor (TCR) gene rearrangement. All patients responded to immunosuppressive therapy.

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