Discussion
Rare cases of primary γδ cutaneous T-cell lymphoma (CTCL) have been reported in children,5 which creates major diagnostic and treatment challenges for pathologists and primary clinicians. Here we describe three unusual pediatric patients with this rare condition and its mimics.
PCGDTCL, a definitive entity in the WHO classification of lymphomas, expresses a mature cytotoxic phenotype with frequent necrosis and/or apoptosis and exhibits diverse histological patterns and clinical symptoms.15 Because of the poor clinical outcome, early diagnosis and aggressive therapy are indicated in these patients. Most PCGDTCL have pathogenic mutations in the JAK-STAT, MAPK, and MYC signaling pathways.16 In contrast, subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a clonal expansion of αβ cytotoxic T-cells involving subcutaneous adipose tissue. Patients typically present with subcutaneous nodules, systemic symptoms, and as many as 20% of cases are associated with an autoimmune condition.17 SPTCL patients often respond to immunomodulatory therapy. Only 10-20% SPTCL contain somatic mutations in epigenetic genes and rarely in JAK-STAT signaling pathways. Primary cutaneous γδ T-cell lymphoma is extremely rare in children. Such a diagnosis should always be based on the integration of clinical presentation, morphology, immunophenotype, and genetics. Our first patient demonstrated an indolent clinical course, with negative germline and somatic pathogenic mutations, which argues against an aggressive PCGDTCL, and favor a SPTCL with increased γδ T-cells. It is therefore critical to avoid aggressive chemotherapy in these patients, and instead, commence initial therapy with an immunomodulator.
Mycosis fungoides (MF), a non-Hodgkin T-cell lymphoma of the skin, is the most common primary cutaneous lymphoma. Rare MF contains an increase in γ/δ T-cells, which may represent a subset of the malignant clone or a background reactive population.4 These patients may show a variety of types of MF, ranging from folliculotropic to granulomatous, hypopigmented, pigmented purpuric dermatosis-like, large-cell transformation, and classic patch/plaque. Due to the scarce data in the literature, there is no solid evidence that demonstrates a significant difference in prognosis for patients with γδ type MF versus αβ type MF.16,18 A relatively aggressive disease course for γδ type MF has been reported in one study,19 but not all. Our second patient of γδ type MF shows an indolent clinical course, similar to the αβ type of MF.
As observed in our third patient, γδ T cells can be increased in non-malignant skin lesions, such as pityriasis lichenoides (PL), an inflammatory condition of the skin characterized by waxing and waning eroded and crusted papules.12 PL chronica (PLC) or et variolaformis acuta (PLEVA) mostly arise from αβ T cells, while extremely rare lymphomas derive from γδ T cells.12 The histopathology of γδ type PL appears to be not appreciably different from αβ type PLs. Finally, it is important to note that all three patients show an indolent course.
In summary, our three cases demonstrated increase in γδ T-cells in malignant and non-malignant skin conditions of children, and all of them showed an indolent clinical course. In borderline case like our first patient, NGS studies may be helpful to establish the diagnosis and avoid aggressive therapies. However, biological and collaborative studies of these unusual and rare disorders are needed in future.