Indurated Plaques in an Otherwise Healthy Child

An 11-year-old male presented with a 1-month history of a painful right thigh lesion. He had no fever, fatigue, or weight loss. He did not improve with oral cefuroxime (500 mg, twice daily, for 10 days). Examination revealed an indurated erythematous plaque over the right inner thigh (Figure 1). His right cheek was swollen, erythematous, and indurated. There was no lymphadenopathy. Complete blood count, biochemistry, and immunological investigations (ANA, C3, C4, immunoglobulin levels) were unremarkable. Magnetic resonance imaging (MRI) demonstrated subcutaneous edema over his right thigh. Positron emission tomography-computed tomography (PET-CT) revealed high metabolic activity in the right cheek and the right thigh. An incisional biopsy was taken from the thigh lesion (Figures 2-4). Diagnosis: Subcutaneous panniculitis-like T-cell lymphoma. The epidermis had focal, minimal vacuolar change (Figure 2, H&E, ×10; Figure 3, H&E, ×20). In the dermis and subcutaneous tissue, there was a dense infiltrate involving fat lobules, with histiocytes and lymphocytes, and rimming of adipocytes (Figure 4, H&E, ×100). Some lymphocytes were atypical with nuclear hyperchromasia. Immunohistochemical staining highlighted CD3, CD8, T-cell receptor (TCR) α/β, and T-cell intracytoplasmic antigen (TIA). Alcian blue stain did not show mucin deposition. Ki-67/MIB-1 labeling index was found to be 30%. TCR gene-rearrangement studies showed clonality. Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare cutaneous lymphoma, sometimes associated with a germline mutation in HAVCR2, encoding TIM3 protein, an inhibitory receptor on T cells. SPTCL presents with progressive, subcutaneous nodules on the extremities, sometimes with ulceration. Fever, fatigue, and weight loss are common, and about 20% of patients present with hemophagocytic lymphohistiocytosis syndrome (HLH) [1]. Those with a HAVCR2 mutation have an increased risk of HLH and severe disease [2]. Histopathologically, there are subcutaneous infiltrates simulating lobular panniculitis composed of small, medium-sized, or sometimes large pleomorphic T cells with hyperchromatic nuclei. Rimming of individual fat cells by neoplastic T cells is a diagnostic feature [3]. Necrosis may be seen. SPTCL has a TCRα/β+, CD3+, CD4−, CD8 + T-cell phenotype, with expression of cytotoxic proteins (TIA, perforin). TCR gene rearrangement studies can be monoclonal or polyclonal. Based on the few published cases, the clinical and pathological features in pediatric SPTCL are very similar to SPTCL in adults with a lack of therapeutic guidelines [4]. As in adults, germline mutations of HAVCR2 are associated with an increased risk of HLH in SPTCL, and these patients may require more intensive therapy. However, owing to a scarcity of reports, a conclusion about the incidence of HLH in affected children cannot be drawn. Treatment focuses on halting atypical T-cell proliferation and restoring immune balance. Indolent cases respond well to prednisone or immunosuppressant therapy such as methotrexate or cyclosporine A. Severe cases or cases with concurrent HLH may require combination chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP] or CHOP-like regimen) [5]. An excellent response to cyclosporine A has been shown in relapsed and refractory SPTCL [5]. Other options include pralatrexate, histone deacetylase inhibitors, or stem cell transplantation. SPTCL generally has a good prognosis and outcome with a 5-year overall survival rate of 85%–91% [5]. SPTLC must be distinguished from lupus panniculitis (LP) and may present similarly to deep morphea and eosinophilic cellulitis. LP is a rare subtype of lupus erythematosus, which simulates SPCLT clinically, but histopathologically is characterized by lobular panniculitis with prominent lymphoid germinal centers and dermal mucin deposition, hyaline fat necrosis, an interface dermatitis, and a positive lupus band on direct immunofluorescence [6]. SPTCL may arise secondarily in long-standing LP [7], as approximately 20% of SPTCL cases are associated with a prior autoimmune disorder, most commonly lupus erythematosus [3]. SPTCL and LP may represent a spectrum of cutaneous T-cell lymphoid dyscrasias, in which atypical lymphocyte lobular panniculitis (ALLP) is a concomitant presentation or overlap between the two disorders, lacking definitive diagnostic features of LP but excluding a clear diagnosis of SPTCL [3, 7]. Both are rare in children. Histopathologically, deep morphea shows inflammation and sclerosis of the deep dermis and subcutaneous fat [8]. Eosinophilic cellulitis shows a dermal infiltrate of eosinophils and histiocytes with “flame figures,” and may have peripheral eosinophilia [9]. Our patient received prednisone (1 mg/kg) and cyclosporine A 150 mg twice daily (3 mg/kg) with good response after 2 weeks and resolution of findings over a 7-month period during which the prednisone dose was tapered. When the prednisone dose was 5 mg daily, a small painful subcutaneous mass appeared on the right thigh and the dose was increased (20 mg/day), and cyclosporine was replaced by methotrexate 15 mg, once weekly with regression of the lesion. Notably, sequencing of the HAVCR2 gene was negative. The authors declare no conflicts of interest.