Angioimmunoblastic T-cell lymphoma (AITL) is an uncommon subtype of
Peripheral T-cell lymphomas (PTCLs) in children with less than 20 cases
reported in the literature. In this paper, we present a case of AITL in
a three years old male with Ataxia-Telangiectasia which regressed
spontaneously without any therapy. A comprehensive review of the
literature regarding treatment and outcome of pediatric patients with
AITL has been also discussed in this article.
Introduction:
Peripheral T-cell lymphomas (PTCLs) are extremely rare in children and
adolescents. They represent less than 2% of all childhood Non-Hodgkin’s
Lymphoma (NHL)1 and divided into 28 subtypes by the
2016 World Health Organization Classification System2.
Although the outcome of pediatric patients with PTCLs appears to be
inferior to that of adult patients, the survival rates are still poor
compared to other NHL types1. The management of this
type of lymphomas in children remains challenging and no standard
treatment strategy has been defined3.
Here, we present a case of AITL in a 3-year-old pediatric patient with
Ataxia-Telangiectasia who improved spontaneously without any
chemotherapy.
Case Presentation:
In 2018, a 3-year-old male patient sought medical advice because of
unsteady gait and recurrent upper respiratory tract infections. The
diagnosis of Ataxia-Telangiectasia was confirmed at that time by
identifying a novel homozygous mutation in the ATM gene. He presented
again within few months of diagnosis with a one-week history of fever
and cough. On physical examination, he had submandibular, cervical,
axillary, and inguinal enlarged lymph nodes with no detectable
hepatosplenomegaly. His chest X-ray showed bilateral perihilar
peri-bronchial wall thickening without mediastinal widening. The
abdominal ultrasound was unremarkable. Laboratory tests revealed severe
neutropenia (neutrophil count 0.2 × 109/L) with total
white blood cells (WBC) of 3.9 × 109/L, hemoglobin
(HB) of 9 g/L, and platelets count (PLT) of 214 ×
109/L. His lactate dehydrogenase (LDH) was 275 U/L,
and Epstein-Barr Virus (EBV) VCA (Viral Capsid Antigen) antibodies IgM
were negative. Due to the presence of neutropenia and high suspicion of
malignancy in patients with primary immunodeficiency, the patient
underwent a right axillary lymph node excisional biopsy. Microscopic
analysis demonstrated infiltration with atypical lymphoid cells having
small, medium to large nuclei and clear cytoplasm localized around high
endothelial venules. Immunohistochemical stains showed positivity of the
atypical lymphoid cells for CD3, CD4, CD10, BCL6, and PD1 (FIGURE 1).
The morphology and immunophenotype were both suggestive of AITL. The
diagnosis was confirmed by molecular studies, which revealed detection
of clonal T cell receptor gamma chain gene rearrangement as well as
clonal B cell IgH/Kappa chain gene rearrangement. His bone marrow biopsy
did not show any lymphomatous involvement.
The patient was planned for chemotherapy with CHOP protocol:
cyclophosphamide, doxorubicin, vincristine, and prednisone. Surprisingly
before treatment initiation, he showed complete recovery of symptoms
with absence of fever and regression of all previously affected lymph
nodes. Therefore, the decision was taken to manage the patient
conservatively with close observation and follow‑up after extensive
discussion with the parents and additional multidisciplinary team
review. Since then, the patient remains asymptomatic, apart from EBV
reactivation which was detected 1 year ago and was managed by several
doses of Rituximab. The patient was still in remission at the last
follow-up, 4 years from diagnosis.
Discussion:
PTCL is a very rare aggressive type of NHL in
children1. It originates from mature T cells in the
thymus and has rearrangement of T-cell receptor genes. The most common
subtype in children is peripheral T-cell lymphoma–not otherwise
specified, other reported phenotypes include Hepatosplenic T-cell
lymphoma, subcutaneous panniculitis-like T-cell lymphoma, extra-nodal
NK/T-cell peripheral T-cell lymphoma and AITL4.
AITL, formerly known as angioimmunoblastic lymphadenopathy with
dysproteinemia (AILD), was believed to be a benign immune response. It
is now recognized as a subtype of PTCL5. There are
only few cases of pediatric patients with AITL reported in the
literature1. The first case was reported in 1976 by
Howarth and Bird. They described a 7-year-old male who presented
initially with fever and generalized lymphadenopathy and then died due
to disease progression 13 months after diagnosis6. In
1981, Fiorillo et al reported the first case of AILD in childhood with
spontaneous improvement7. Another case of AILD in a
14-month-old baby was reported by de Terlizzi et al. The patient died
due to disease recurrence 100 months after initial
presentation8. Horneff et al described neurological
complications in a 13-year-old girl with AILD9. In a
retrospective analysis of non-anaplastic peripheral T-Cell lymphoma in
pediatric patients in Japan, Kobayashi et al reported one case of AITL
in a 14-year-old male10. In a study of childhood PTCL
in the United Kingdom, there were 3 cases of pediatric patients with
AITL4. In the latest international review of 143 cases
of pediatric PTCL, 4 patients had AITL11. Kraus et al
reported a case of AITL in a pediatric patient post heart transplant
presenting with cranial nerve palsy 12. To our
knowledge, this is the first case report describing AITL in a pediatric
patient with Ataxia-Telangiectasia evolved toward spontaneous remission.
Characteristics, treatment, and outcome of the previously described
patients (including our case) are shown in (TABLE 1).
There is no consensus about the optimal treatment for pediatric PTCL due
to the absence of randomized clinical trials and the rarity of cases in
pediatric patients3. Chemotherapy options include NHL
or Acute Lymphoblastic Leukemia (ALL) regimens11. The
United Kingdom Children’s Cancer Study Group (UKCCSG) reported a
superior outcome of ALL–like therapy compared to NHL
therapy4.
The association between other types of NHL and immune deficiency is well
known. Many cases of AILD/AITL after immunosuppressive therapy have been
reported in adults 13-14. In the retrospective
EICNHL/i-BFM analysis of 143 children, pre-existing conditions such as
primary immune deficiency, immune suppressive therapy and/or previous
transplantation were found in 25 % of the patients. A better outcome
was observed in those patients 11. Our patient was
diagnosed with Ataxia-Telangiectasia 1 year before developing AITL.
Spontaneous regression of malignancies is a fascinating phenomenon. It
is defined as the complete or partial disappearance of cancer in the
absence of anti-neoplastic therapy 15. It was first
described by Sir William Osler in 1906 16 and has been
reported in patients with low grade non-Hodgkin’s lymphoma17. The exact mechanism of this phenomenon remains
unclear and most likely can be explained by immunological factors18. Among pediatric patients with PTCL, only 12 cases
with spontaneous regression have been reported in the literature. They
are summarized in (TABLE 2).
Conclusion:
In summary, this is the first case report of spontaneous improvement of
Angioimmunoblastic T-cell lymphoma in a 3-year-old pediatric patient
with Ataxia-Telangiectasia. Due to paucity of cases of AITL in children,
international collaboration is certainly needed to establish the best
treatment recommendations to guide clinicians and pediatric oncologists
worldwide.
Conflict of interest statement:
Authers declare there is no conflict of interest.
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FIGURE 1: The lymph node biopsy findings and immunophenotypic features:
-Effacement of lymph node architecture Hematoxylin-eosin (H&E) Stain.4X
(A).
-Atypical lymphoid cells with high endothelial venules proliferation.
H&E stain.20X.(B).
-The neoplastic lymphocytes are positive for CD3.10X (C).
-CD21 highlights the expanded follicular dendritic meshwork.4X (D).
-The neoplastic cells are positive for T follicular helper cell markers
including CD10 , BCL6 (E&F respectively, 4x) and PD1 (not shown).
TABLE 1: Characteristics, Treatment and Outcome of Pediatric Patients
with Angioimmunoblastic Lymphoma.