Gastric T-cell lymphoma associated with hemophagocytic syndrome
© Fukui et al; licensee BioMed Central Ltd. 2004
Received: 01 June 2004
Accepted: 19 October 2004
Published: 19 October 2004
Lymphoma-associated hemophagocytic syndrome (LAHS) occurs in mostly extra nodal non-Hodgkin's lymphoma. LAHS arising from gastrointestinal lymphoma has never been reported. Here we report a case of gastric T-cell lymphoma-associated hemophagocytic syndrome.
A 51-year-old woman presented with pain, redness of breasts, fever and hematemesis. Hematological examination revealed anemia. Gastroscopy revealed small bleeding ulcers in the stomach and the computed tomography scan showed liver tumor. She underwent total gastrectomy for gastrointestinal bleeding and the histopathology revealed gastric T-cell lymphoma. She continued to bleed from the anastomosis and died on the 8th postoperative day. Autopsy revealed it to be a LAHS.
If Hemophagocytic syndrome (HPS) occurs in lymphoma of the gastrointestinal tract, bleeding from the primary lesion might be uncontrollable. Early diagnosis and appropriate treatment are needed for long-term survival.
Hemophagocytic syndrome (HPS) in adults is characterized by reactive and systemic proliferation of benign histiocytes that phagocytose blood cells . It is often associated with infections, malignant neoplasms, autoimmune diseases and various immunodeficiencies. Lymphoma-associated hemophagocytic syndrome (LAHS) mostly occurs from extra nodal lymphoma and is known to have a poor prognosis. Here we report a case of LAHS arising from gastric lymphoma with a fulminant clinical course and difficult diagnosis until the time of autopsy.
Diagnostic criteria for adult lymphoma associates hemophagocytic syndrome (LAHS)
1 High fever for more than a week (peak 38.5°C)
2 Anemia (Hb < 9 g/dl) or thrombocytopenia (platelet < 100,000 μ/l)
3 a) LDH ≥ 2 × upper limit
b) Hyperferritinemia (≥ 1,000 ng/dl)
c) Hepatosplenomegaly on CT, US or MRI
d) FDP ≥ 10 μg/ml
4 Hemophagocytosis in bone marrow, spleen or liver
5 No evidence of infection
6 Histopathologically confirmed malignant lymphoma
A diagnosis of LAHS requires that all of the above conditions are fulfilled.
Of the item 3, at least two of the four sub-items (a~d) should be fulfilled.
When item 1 to item 5 are present for 2 weeks and glucocorticoid or γ-globulin therapy is not effective, a diagnosis of probable LAHS can be made and chemotherapy against malignant lymphoma can be started.
In Japan, T-cell LAHS accounts for 48.5% of all adult LAHS . T-cell LAHS mostly occurs in extra nodal, especially nasal, cutaneous, or malignant lymphoma involving liver and spleen. There have been no reports on LAHS from gastric lymphoma. As the diagnosis in the present case was made at autopsy it is not clear as to when the HPS occurred initially. One possibility is the setting of disseminated T-cell lymphoma. This is supported by the patient's fever, which continued for one month, liver dysfunction, and coagulopathy, which existed from the initial stage of the disease, however the bone marrow did not show any lymphoma infiltration. It could also be considered that the hemophagocytic syndrome occurred as a result of the surgery as pancytopenia and hepatosplenomegaly were not observed before the operation and hemophagocytosis was not recognized on histopathological examination in the resected stomach. In T-cell lymphoma, the hemophagocytic syndrome is assumed to be caused by cytokines, especially, tumor necrosis factor-α, and interferon-γ released from neoplastic T-cells [4, 6]. Uncontrolled secretion of cytokines may stimulate the proliferation and phagocytic activity of macrophages. It seems likely that hypercytokinemia due to surgical resection might have contribute to the development of HPS in the present case. In our opinion the former is more likely however based on the findings of this case the second hypothesis too cannot be rejected.
The poor prognosis of LAHS, especially T-LAHS, is well known. The median survival time from the diagnosis is reported to be 143 and 69 days respectively in Japan . For LAHS prompt initiation of treatment with multi agent chemotherapy is required to improve the symptoms and survival . Bone marrow transplantation is considered to be a treatment for chemotherapy-resistant LAHS . The median survival time of LAHS patients without chemotherapy is only 11 days .
In this case, the initial presentation was mastalgia and hence it took a considerable amount of time to reach a diagnosis. Furthermore, bleeding from the anastomosis continued leading to a rapidly progressive fatal clinical course.
In HPS occurring in lymphoma of the gastrointestinal tract uncontrollable bleeding from the primary lesion might occur. Therefore, an earlier diagnosis of HPS should be made by bone marrow aspirates, and appropriate treatments should be started as soon as possible. Surgery if performed, must be performed with utmost caution.
LAHS could also occur from lymphoma of the gastrointestinal tract. For long-term survival; early diagnosis and appropriate treatment are needed. Surgery if performed without a proper diagnosis could prove fatal.
Permission of patient's relatives was obtained for publication of her case records
- Wong KF, Chan JKC: Reactive hemophagocytic syndrome-A clinicopathologic study of 40 patients in an Oriental population. Am J Med. 1992, 93: 177-180. 10.1016/0002-9343(92)90048-G.View ArticlePubMedGoogle Scholar
- Henter JI, Elinder G, Ost A, and the FHL study group of the histiocyte society: Diagnostic guidelines for hemophagocytic lymphohistiocytosis. Semin Oncol. 1991, 18: 29-33.PubMedGoogle Scholar
- Yao M, Cheng AL, Su IJ, Lin MT, Uen WC, Tien HF, Wang CH, Chen YC: Clinicopathological spectrum of haemophagocytic syndrome in Epstein-Barr virus-associated peripheral T-cell lymphoma. Br J Haematol. 1994, 87: 535-543.View ArticlePubMedGoogle Scholar
- Tsuda H: Hemophagocytic syndrome in children and adults. Int J Hematol. 1997, 65: 215-226. 10.1016/S0925-5710(96)00560-9.View ArticlePubMedGoogle Scholar
- Takahashi N, Chubachi A, Miura I, Nakamura S, Miura BA: Lymphoma associated hemophagocytic syndrome in Japan [Japanese]. Jpn J Clin Hematol. 1999, 40: 542-549.Google Scholar
- Lay JD, Tsao CJ, Chen JY, Kadin ME, Su IJ: Upregulation of tumor necrosis factor-α gene by Epstein-Barr Virus and activation of macrophages in Epstein-Barr Virus-infected T cells in the pathogenesis of hemophagocytic syndrome. J Clin Invest. 1997, 100: 1969-1979.PubMed CentralView ArticlePubMedGoogle Scholar
- Imasyuku S: Differential diagnosis of hemophagocytic syndrome: underlying disorders and selection of the most effective treatment. Int J Hematol. 1997, 66: 135-151. 10.1016/S0925-5710(97)00584-7.View ArticleGoogle Scholar
- Hasegawa D, Sano K, Kosaka Y, Hayakawa A, Nakamura H: A case of hemophagocytic lymphohistiocytosis with prolonged remission after syngeneic bone marrow transplantation. Bone Marrow Transplant. 1999, 24: 425-427. 10.1038/sj.bmt.1701917.View ArticlePubMedGoogle Scholar
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