Blood, Vol. 92 No. 6 (September 15), 1998:
pp. 2182-2183
CORRESPONDENCE
Detection of Antibodies to Fasciola and
Anisakis in Japanese Patients With Intravascular
Lymphomatosis
 |
LETTER |
To the Editor:
Recently, we reported five Japanese patients with large B-cell lymphoma
associated with hemophagocytic syndrome, ie, malignant histiocytosis-like B-cell lymphoma, and suggested that they might be
regarded as an aggressive variant of intravascular lymphomatosis (IVL)
based on the localization of tumor cells within the sinus and vessels
of the involved organs.1 Phenotypically, these lymphomas
were CD5
, CD10, CD19+,
CD20+, and HLA-DR+, with monoclonal
rearrangement of the Ig heavy chain gene in two cases. They were also
clinically characterized by onset in middle age or old age, fever,
anemia, thrombocytopenia, hepatosplenomegaly, initial involvement of
the bone marrow, hemophagocytosis, and a rapidly aggressive clinical
course. Lymphadenopathy, skin lesions, neurological abnormalities, or
peripheral blood lymphocytosis were rarely observed during the entire
clinical course. Laboratory examinations showed elevated levels of D-D
dimer, lactate dehydrogenase, C-reactive protein, interleukin-6 (IL-6),
and the soluble IL-2 receptor isoforms, but not IL-1
, IL-2, or tumor
necrosis factor-
, with serologic evidence of abnormal immune
function such as circulating antinuclear antibody. Interestingly, more
than 30 cases of malignant histiocytosis-like B-cell lymphoma or IVL
with hemophagocytic syndrome have been reported exclusively in Asian
patients, with only a few cases in Western patients, and their clinical
features appeared to differ considerably from those of typical IVL in
Western countries. We therefore proposed that this group should be
called an Asian variant of IVL (AIVL). In our series, antibodies
against human T-cell lymphotropic virus type-I were negative, and
Epstein-Barr virus was not detected by in situ hybridization. Notably,
in one of the autopsied cases (case no. 5 in our previous report),
circumscribed egg granulomas of Schistosoma japonicum were
observed to be distributed among the lymphoma cells in the liver (Fig
1). This unusual finding prompted us to perform a
seroimmunological survey for helminthous infections associated with
AIVL, because some parasites, as well as viruses, most likely play an
important role in the etiology of several endemic lymphoproliferative
diseases.2-4
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| Fig 1.
A circumscribed egg granuloma of Schistosoma
japonicum among the lymphoma cells in a portal area of the liver.
Sinusoidal involvement of the lymphoma cells is also evident.
Hematoxylin and eosin stain; original magnification ×200.
|
|
In the present study, all five patients with AIVL had lived for at
least 20 years in suburban areas of Toyota, which is located in the
central part of Japan. No patient showed eosinophilia or a high titer
of total IgE. Informed consent was obtained from all patients or their
families. Enzyme immunoassays for the detection of antibodies to
Echinococcus (IgG and M), Trichinella (IgG, M, and A), Filaria (IgG and M), Toxocara (IgG, M,
and A), Strongyloides (IgG), Schistosoma (IgG and
M), and Fasciola (IgG and M) and radioallergosorbent tests
(IgE) for Fasciola, Schistosoma, and Anisakis
were performed at Specialty Laboratories (Santa Monica, CA). The titers
of anti-Fasciola IgG and anti-Anisakis IgE were
judged as positive in four (3.2 to 5.3 SD) and three (1.03 to 11.2 kU/L) of five patients with AIVL, respectively. Among these,
anti-Fasciola IgM was also positive in the case with the
highest titer of anti-Fasciola IgG. Anti-Toxocara IgG and M, together with anti-Fasciola IgG and
anti-Anisakis IgE, was detected in another patient. All
other antibodies were negative in the AIVL patients. As a control, the
sera of 19 age- and habitat-matched patients with conventional large
B-cell lymphoma were tested for anti-Fasciola IgG and
anti-Anisakis IgE (Table 1). The
percentage of anti-Fasciola IgG in the patients with AIVL
(4/5 [80%]) was significantly higher than that in the control
patients (1/19 [5%]). The presence of anti-Anisakis IgE
in patients with AIVL (3/5 [60%]) tends to be more frequent than
that in the control group (7/19 [37%]), but not at a significant
level.
The present seroimmunological study indicates a positive relationship
between Fasciola infection and AIVL. Although we could not
find studies regarding carcinogenecity of Fasciola, the
tumor promoting activity of the flukes in related genera, such as the genus Schistosoma, has been well reported.1 In
addition, S mansoni was reported recently to be a possible
pathogenic cofactor of Burkitt's lymphoma in Brazil.5
Anisakis, known as the sushi worm, is a tissue-penetrating
nematode that causes acute zoonoses6 and may be a cofactor
of gastric cancer.7 It is noted that the geographical
distribution of these helminthous infections covers Asia. Further
investigation of the association of AIVL with the infections of
Fasciola, Schistosoma, or Anisakis may contribute
to elucidation of the pathogenesis of AIVL.
Takuhei Murase
Department of
Hematology
Kazuhiro Tashiro
Department of
Pathology
Takashi Suzuki
Department
of Gastroenterology
Toyota Memorial Hospital
Toyota,
Japan
Hidehiko Saito
1st Department of Internal
Medicine
Nagoya University
Nagoya, Japan
Shigeo Nakamura
Department of Clinical Laboratories and
Pathology
Aichi Cancer Center
Nagoya, Japan
| |
ACKNOWLEDGMENT |
We thank Prof Moriyasu Tsuji (Kyorin University, Tokyo, Japan) for
helpful comments.
| |
REFERENCES |
1.
Murase T,
Nakamura S,
Tashiro K,
Suchi T,
Hiraga J,
Hayasaki N,
Kimura M,
Murakami M,
Mizoguchi Y,
Suzuki T,
Saito H:
Malignant histiocytosis-like B-cell lymphoma, a distinct pathologic variant of intravascular lymphomatosis: A report of five cases and review of the literature.
Br J Haematol
99:656,
1997[Medline]
[Order article via Infotrieve]
2.
Cheever AW:
Schistosomiasis and neoplasia.
J Natl Cancer Inst
61:13,
1978
3.
Tajima K,
Fujita K,
Tsukidate S,
Oda T,
Tominaga S,
Suchi T,
Hinuma Y:
Seroepidemiological studies on the effects of filarial parasites on infestation of adult T-cell leukemia virus in the Goto islands, Japan.
Jpn J Cancer Res (Gann)
74:188,
1983
4.
Facer CA,
Playfair JHL:
Malaria, Epstein-Barr virus, and the genesis of lymphomas.
Adv Cancer Res
53:33,
1989[Medline]
[Order article via Infotrieve]
5.
Araujo I,
Foss HD,
Bittencourt A,
Hummel M,
Demel G,
Mendonca N,
Herbst H,
Stein H:
Expression of Epstein-Barr virus gene products in Burkitt's lymphoma in northeast Brazil.
Blood
87:5279,
1996[Abstract/Free Full Text]
6.
Gutiérrez Ramos R,
Tsuji M:
Detection of antibodies to Anisakis simplex larvae by enzyme-linked immunosorbent assay and immunoelectrophoresis using crude or purified antigens.
J Helminthol
68:305,
1994[Medline]
[Order article via Infotrieve]
7. (letter)
Petithory JC,
Paugam B,
Buyet-Rousset P,
Paugam A:
Anisakis simplex, a co-factor of gastric cancer?
Lancet
2:1002,
1990
