Case report
Lymphocyte Rich Hodgkin's Lymphoma Presenting with Immune
Pancytopenia: A Case Report and Literature Review.
Dr. I. A. Adam1, Dr. O. H.Musa1, Dr. A. Kordofani2, Dr. L. Gafaar2
We report a case of LRHL presenting with autoimmune pancytopenia that resolves after
steroid and four cycles of ABVD chemotherapy. Review of the literature revealed 3 previous cases
of same histological type with AIHA; however immune pancytopenia has not been reported so far.
Clinicians should consider cHL as possible differential in patients affected by what is thought to be
idiopathic AIHA. More data recruitment and analysis are very crucial to exactly define the
pathophysiology of this rare entity.
1- Introduction:
Hodgkin's disease is an uncommon, but, currently highly curable disorder
accounting for ten percent of all diagnosed lymphoma, and only approximately one
percent of cancer registered in developed countries each year. Fatigue is almost
constantly seen at the time of diagnosis mostly secondary to anaemia. The pathogenesis
of anaemia varies; it could be secondary to chronic disease reflecting the underlying
malignancy. In advanced disease, anaemia occurs from marrow suppression by the
infiltrating malignant cells. It can be iatrogenic due to bone marrow suppression by
chemotherapeutic agents. Rarely does it result from autoimmunehaemlolytic process.
Autoimmune haemolytic anaemia (AIHA) is rarely seen in Hodgkin's lymphoma with
reported incidence of 0.2- 4.2%. reported cases and literature reviews have shown that
when AIHA occurs in HL, it happens mostly at stages III and IV of nodular sclerosis HL
(NSHL) or mixed cellularity HL (MCHL). Here, we discuss a case of lymphocyte rich
HL (LRHL) with immune pancytopenia [1-8].
2- Case Report:
A thirty six year old Sudanese male presented complaining of generalized fatigue,
fever, palpitations and mild loss of weight for three months. He also mentioned a
history of similar condition few months ago which was diagnosed as malaria
complicated by anaemia and was treated accordingly. No past medical history or family
history of note. Examination revealed severe pallor, jaundice, and generalized
lymphadenopathy including cervical, axillary, and inguinal groups, but, no
hepatosplenomegally. Examination of the chest, cardiovascular system, abdomen, and
central nervous system was unremarkable. The CBC revealed WBC 2500 x 109 /L,
neutrophils 800 x 109 /L, Hb 6.8 g/dl, MCV 112.8 fl, platelets 22000x109/L, and
reticulocytes 16%. Lactate dehydrogenase (LDH) was high at 348 U/L, total bilirubin
was 1.47 mg/dl mainly direct. Direct Coomb's Test (DAT) was strongly positive (+++).
Other biochemical profiles were normal. Bone marrow aspiration and biopsy showed
no evidence of malignant infiltration, but, revealed marked trilineage hyperplasia,
especially of erythropoiesis consistent with a haemolytic process. In the interim a
biopsy from axillary lymph node was taken for histopathological assessment.
1
Abdominal sonography and chest X-ray were normal. The patient was admitted,
transfused two units of PRBC, 6 units of platelets, and started intravenous methyl
prednisolone. A prompt increase of platelets to 66000x 109 /dl and then to 202000x109
/dl within one week was appreciated, by that time, the histopathological report was
obtained and demonstrated an effaced architecture with numerous small cells, large
Reed- Sternberg cells, few eosinophils and neutrophils. Immunohistochemical stains
indicated RS cells being positive for CD30 and CD15 and negative for CD45 (LCA) and
CD20. Biopsy results were interpreted as classical lymphocyte rich Hodgkin's
lymphoma.
Table 1-1: Laboratory data of our patient.
Variables
Haemoglobin (g/dl)
Reticulocyte %
WBC ( x 109/L)
Neutrophils (x109/L)
Platelets (x109/L)
T. bilirubin(mg/dl)
D.bilirubin (mg/dl)
LDH (IU/L)
Direct Coomb's test
0n
admission
6.8
16
2.5
0.8
22
1.47
0.51
348
+++
1 week of
steroid
9.6
Following
End of 3th
st
the 1
cycle of cycle of ABVD
ABVD
7.8
7
4.9
3.2
202
4.1
2.9
66
10.5
2.7
1.3
224
243
3- Results:
The patient was started on ABVD (Adriamycin, bleomycine, , vinblastine, and
dacarbazine) chemotherapy, and has so far completed four cycles and showed both
clinical improvement in terms of symptoms and signs, and laboratory improvement i.e.
resolution of immune cytopenia.
4- Discussion:
Lymphocyte rich HL represents about 1% of cases, typically found in older
individual with early stages (I or II). Bulky disease, B symptoms and extra-nodal
involvement are not typical for this class, so our patient displayed a unique clinical
presentation by exhibiting both B symptoms and advanced disease stage (stage III) [2,911]. Fifty four percent of AIHA in adults are secondary to underlying diseases such as
autoimmune diseases and malignancy. The relationship of AIHA with classical HL
(cHL) has been recognized for more than forty years; however there is no extensive
primary literature that has characterize this association , except for sporadic reported
cases. Q. Feng and colleague recently reviewed 40 published cases including 8
paediatric, of HL with AIHA and summarized the general, clinical and pathological
characteristics. Our patient differs from all of their reported cases, in the fact that he
presented with immune pancytopenia rather than isolated AIHA or ITP. DCT was
positive in 93% of their patients, mostly specified as IgG and/or C3. Our patient had
appositive DCT, but antibody specificity was not tested. Regarding the pathological
2
subtypes MCHL and NSHL were the most common encountered classes in their series
48% and 34% respectively, while only 10% of cases were similar to our case i. e. LRHL (3
cases). The higher incidence of AIHA in MCHL and NSHL is reasoned out by their
higher incidence compared with other subtypes. AIHA is the onset symptom in 40% of
cases,; according to the same series, but it may precede the disease. Its development in
patient previously treated for HD indicate relapse of the disease. Some authors claimed
that steroid treatment may masks HL clinical courses making it difficult to diagnose,
lack of regular follow-up may also delay diagnosis [3,12,13]
It was not clear how autoantibody production is induced in AIHA. Normally low
titer of autoimmunogenic IgM are found in healthy individual. It is postulated that Bcell clone that produce these antibodies lose their regulation mechanisms and switch to
produce high titer. Other studies suggested a role of T-cell deregulation in
pathogenesis. This theory arises from observations in paediatric patients with
autoimmune lymphoprliferative syndrome, these individuals have a defective Fasreceptor-mediated lymphocyte apoptosis making them susceptible for repeated
episodes of AIHA and other autoimmune cytopenias. In other patients AIHA seems to
be triggered or exacerbated by viral infection. Less common causes includes posttransplant, post-transfusion and drugs such as cephalosporins [14,15]
The pathophysiology of AIHA that arises during the course of malignancies, most
commonly CLL, remains mysterious. Some researchers have suggested that it is a
paraneoplastic syndrome that develops secondary to the aberrant production of
hormones, cytokines, or autoantibodies by neoplastic cells. It has been also
hypothesized that these antibodies cross react with the red blood cells leading to their
destruction. These assumptions are based on the clinical observation that AIHA
responds well to chemotherapy and steroids, readily resolving shortly after treatmentis
started. In addition, sporadic population based studies have demonstrated the presence
of AIHA in patients later diagnosed with HD. Clonal lymphocytes have been identified
in individual with apparently idiopathic AIHA as well. They may or may not develop
lymphoma in the future. These findings support the theory that AIHA could result from
a syndrome of a clinically silent Hodgkin's or non-Hodgkin's lymphoma. It is not clear
why sometimes AIHA manifest after successful treatment and when the patient is in
complete remission. Further studies are needed to explain these observations[3, 10, 13, 17,
18].
Among 40 reported cases the predominant treatment was combination of steroid,
chemotherapy, and radiation, albeit few cases showed spontaneous recovery or respond
to steroid treatment alone[13]. Our patient showed excellent initial response to steroid
which is followed by chemotherapy.
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