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.