T-Cell Rich B-Cell
Lymphoma A diagnostic dilemma in paediatric oncology
Bhattacharya A.1, Latha
M. S.2, Julius X. Scott3
1Dr. Adhiraj Bhattacharya, Intern, 2Dr. Latha M. Sneha, Assistant
Professor, 3Dr. Julius X. Scott, Professor of Paediatrics and Head of
Division of Paediatric Hematology and Oncology, all authors are
affiliated with Division of Pediatric Hemato Oncology, Department of
Paediatrics, Sri Ramachandra Medical College Research
Institute, No.1, Ramachandra Nagar, Porur, Chennai, India.
Address for
Correspondence: Dr. Latha M.S., Assistant Professor,
Division of Pediatric Hematology Oncology, Department of
Pediatrics, Sri Ramachandra Medical Centre, No.1, Ramachandra Nagar,
Porur, Chennai, India, E-mail: drmslatha@yahoo.com
Abstract
T-cell rich B-cell lymphoma, most commonly seen in adults and rarely
reported in children is a type of Diffuse Large B cell Lymphoma.
(DLBCL). It has several clinical, histological and immunohistochemical
similarities to commonly Nodular lymphocyte predominant
Hodgkin’s lymphoma. We report an 8 year-old boy who presented
with a swelling over the right inguinal region for two
months. FNAC of the swelling was inconclusive. MRI abdomen
revealed multiple masses in right iliac fossa. Immunohistochemistry of
the biopsy mass was consistent with T cell rich B
cell lymphoma. T cell rich B cell lymphoma has a very low incidence in
pediatric population and still remains unrecognized in most of the
cases. When compared to adults, children have a better
prognosis and hence stronger emphasis on immunohistochemistry is
essential. Careful attention should be paid to differentiate the
different neoplasms as each have a distinct course of clinical history
and different therapies.
Keywords:
T-cell rich B-cell lymphoma, Child, Hodgkin’s lymphoma,
Immunohistochemistry
Manuscript received:
10th September 2017,
Reviewed: 18th September 2017
Author Corrected: 25th
September 2017, Accepted
for Publication: 30th September 2017
Introduction
T-cell rich B-cell lymphoma (TRBCL) is considered a rare variant of
aggressive B-cell lymphoma described by few neoplastic B-cells in a
background of numerous benign T lymphocytes and
histiocytes [1]. Not widely recognized in pediatric
population, due to its extensive infiltrate of reactive T cells,
causing diagnostic dilemmas, only few cases are reported. Often
misdiagnosed as classical Hodgkin lymphoma or nodular lymphocyte
predominant Hodgkin lymphoma or reactive lymphadenopathies, this entity
should be recognized in pediatric age group, as a less aggressive
treatment results in relapses. When diagnosed accurately, children
respond well to chemotherapy and exhibit good prognosis. We report a
case of an 8 year old boy presenting with an inguinal swelling and
abdominal mass which was initially thought to be Nodular lymphocyte
predominant Hodgkins lymphoma and later confirmed by IHC as T cell rich
B cell lymphoma, treated as per LMB 96 protocol and is in remission now
for 4 years.
Case
Report
An 8 year old boy presented with a swellingover the right inguinal
region for a period of two months. The swelling was slowly
progressive with an increase in the size of the lesion over last two
weeks. There was no history of trauma, fever loss of
appetite, weight loss, or night sweats. There was also no
contact history of tuberculosis. On examination there was no
generalized lymphadenopathy or hepatosplenomegaly. A 1 x 2 cms mass
could be felt over the right inguinal region. It was non tender, not
fixed to skin, and firm in consistency. Genital examination was normal.
Baseline investigations including complete blood counts, renal and
liver function tests, AFP levels, HCG levels and serum uric acid were
normal. Serum LDH was elevated (980 units IU/L). Urine VMA was
normal. FNAC of swelling was suggestive of reactive
lymphocytosis. MRI abdomen showed extensivepara-aortic, pre-caval,
retro-caval and peri-pancreatic lymphadenopathy. Multiple soft tissue
masses wereseen in the right iliac fossa, also extending into the right
side of the pelvis, engulfing the iliac vessels. He underwent
laparotomy and excision biopsy of the iliac mass, whichwas
provisionally reported as Hodgkin’s lymphoma-Nodular
lymphocyte predominant type. By immunohistochemistry the
atypical cells were immune positive for CD20 and PAX-5, negative for
CD30, CD15, ALK-1 and LMP, while the background cells were positive for
CD3 and CD68, making it most consistent with T cell rich B cell
lymphoma. Bone marrow examination and CSF analysis was normal. The
patient was started on chemotherapy as per LMB 96 (Group B) protocol
and PET CT after 4 cycles of chemotherapy showed complete resolution.
He completed6cycles andis diseasefree for 4 years.
Discussion
Originally, T-cell-rich B-cell lymphoma (TCRBCL) was introduced to
describe several variants of B-cell lymphomas with a pronounced T-cell
reaction mimicking T-cell lymphoma [2]. The presence of less than 10%
(sometime as low as 1%) of usually large, neoplastic B cells in a
background of numerous T cells was the unifying feature of the
diagnosis. It was originally described as T-cell-rich B-cell lymphomain
1988 by Ramsay et al who reported five cases that had previously been
misdiagnosed as peripheral T-cell lymphoma because of the presence of
several T-cells surrounding a few large B cells [2]. Later in 1992 the
definition was revised by Delabie et alwho introduced the term
histiocyte-rich B-cell lymphoma in characterizing six cases of large
B-cell lymphoma identified by minimal neoplastic B cells amidst a large
population of histiocytes and small lymphocytes [3]. In 2001, the World
Health Organization formally defined TCRBCL as a morphologic variant of
DLBCL characterized by fewer than 10% large neoplastic B cells amid a
prominent inflammatory infiltrate, the majority of which are small
polyclonal T cells, with or without the presence of histiocytes [4]. In
2000, a Children's Cancer Group study reported that out of a total of 86
studied cases, 30% were diagnosed to have DLBCL. Furthermore, only of 6
cases out of these were found to have TCRBCL. The common age group
affected was between the ages of 12-16 [5]. TCRBCL can be similar to
other peripheral B cell lymphoid neoplasms, most commonly nodular
lymphocyte predominant Hodgkin lymphoma (NLPHL) making its
diagnosis pathologically more challenging and thus may attribute to the
low yield in the above mentioned study. The main histopathological differential diagnoses for TCRBCL
areLymphocyte rich classical HL (cHL) and Nodular lymphocytic
predominant Hodgkin’s lymphoma (NLPHL).Classical
Hodgkin Lymphoma (cHL) can be mistaken for TCRBCL due to
similar features of scanty neoplastic cells and abundant host
inflammatory response that is further complicated by the occasional
presence of HRS (Hodgkin Reed-Sternberg)-like neoplastic
cells [6]. The majority of HRS cells are negative for CD45, CD20, and
CD79a and positive for CD15 and CD30 [7]. The reactive cells in cHL
include a high number of small B cells along with other inflammatory
cells, including eosinophils, neutrophils, and plasma cells. The
absence of this inflammatory milieu differentiates TCRBCL from
classical Hodgkins Lymphoma [8].
NLPHL and TCRBCL can be immunophenotypically similar with tumour cells
that are positive for CD20 and CD79a in both. It is the presence of
reactive CD3+ T cells in the background that differentiates both
entities. In addition, the background in NLPHL has CD57+ rosettes and
CD21+ follicular dendritic cells, while TCRBCL shows CD68+ macrophages
[9]. In our case, the HPE reports showed atypical reactive
lymphoid cells that stained positive for CD20, CD79 and CD68 making
this a diagnosis that leaned more towards TCRBCL.
B symptoms, extra nodal involvement and advanced stage disease are
commonly seen in TLCBCL, unlike in other types of DLBCL. NLPHL usually present with isolated cervical or inguinal
lymphadenopathy and are at lower stage at the time of diagnosis
[10]. The child in our case presented with a inguinal lymphadenopathy
but constitutional and B symptoms were absent.
TCRBCL is treated like DLBCL through R-CHOP chemotherapy and children
had better prognosis when compared to adults. Tiemann et al has
reported an event free survival of 86 % and overall survival of 94 %
ata median follow up of 23 months [11]. Those who were misdiagnosed and
treated less aggressively had poor prognosis as they relapsed and had
poor response to salvage therapies thereby highlighting the importance
of accurate diagnosis at presentation [12].
Conclusion
Careful immunohistochemical analysis of both tumour cells and
inflammatory micro environment is essential for accurate diagnosis of T
cell rich B cell Lymphoma in children and adolescents as Hodgkin
lymphoma is also of higher incidence among these age groups and the
histological similarities of these two entities adds to the diagnostic
dilemma.
This case study highlights the difficulties in defining the specific
subtypes of DLBCL and the importance of immunophenotying in accurate
diagnosis of such cases.
Funding:
Nil, Conflict of
interest: None initiated
Permission from IRB:
Yes
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How to cite this article?
Bhattacharya A, Latha M. S, Julius X. Scott. T-Cell Rich B-Cell
Lymphoma– A diagnostic dilemma in paediatric oncology. J
PediatrRes. 2017;4(09):584-587.doi:10. 17511/ijpr.2017.09.08.