Adult T-cell Leukemia/Lymphoma with a Giant Gastric Tumor: A Case Report

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1 Adult T-cell Leukemia/Lymphoma with a Giant Gastric Tumor: A Case Report Shungo Hiroyasu, Masayuki Shiraishi, Masamori Shimabukuro, Toshiomi Kusano and Yoshihiro Muto First Department of Surgery, School of Medicine, University of the Ryukyus, Okinawa A rare case of adult T-cell leukemia/lymphoma with a giant exophytic gastric tumor invading the anterior abdominal wall is presented. The patient was a 52-year-old woman, who had a history of strongyloidiasis. Although the patient was serologically positive for HTLV-I antibody, there were no lymphoma cells in the peripheral blood or systemic lymphadenopathy. After two cycles of combination chemotherapy, the tumor was surgically resected. The pathological diagnosis of the resected specimen was T-cell lymphoma of the diffuse mixed cell type. Flow-cytometric analysis of the lymphoma showed a CD4*and CD8* phenotype. One month after surgery, the patient developed hypercalcemia, resulting in acute renal and respiratory failure, and died. The prognosis of lymphoma-type ATL is known to be extremely poor, and thus we should bear in mind that ATL can take the form of a primary gastric mass without leukemic manifestations. (Jpn J Clin Oncol 26: , 1996) Key words: Adult T-cell leukemia/lymphoma Stomach neoplasm Strongyloidiasis Introduction Since the disease concept of adult T-cell leukemia/lymphoma (ATL) was first introduced by Takatsuki et al. n and Uchiyama et al., 2) a large percentage of peripheral T-cell lymphoma cases have been attributed to this disease entity, particularly in ATL-endemic areas of Japan. 3 ' ATL (acute and lymphoma types) should be treated as an independent category among malignant lymphomas, because its prognosis is extremely poor. 4-5 ' Compared with other types of peripheral T-cell lymphomas, ATL is known to have less gastrointestinal involvement. 6 ' In addition, most gastric lesions of ATL tend to be either invasive or ulcerative." This article reports a rare case of ATL manifested as a primary giant gastric tumor but without evidence of leukemia, which demonstrated an aggressive clinical course. Case Report The patient, a 52-year-old woman, who had lived Received: January 8, 1996 Accepted: April 12, 1996 For reprints and all correspondence: Masayuki Shiraishi, First Department of Surgery, School of Medicine, University of the Ryukyus, Nishihara, Okinawa on Okinawa Island since birth, presented to her family physician with a 2-week history of flu-like symptoms on May 2, Upon examination, a large abdominal mass was observed, and therefore she was referred to our University Hospital three days later. She had a history of strongyloidiasis that had been treated successfully three years-earlier. On physical examination, a hard mass was palpable in the upper abdomen, but no systemic lymphadenopathy was observed. Laboratory examination revealed an elevated LDH level of 1664 IU/1, and positivity for human T-cell lymphotrophic virus type 1 (HTLV-1) antibody. A peripheral blood examination showed a normal WBC count and a normal lymphocyte ratio with no atypical cells. No lymphoma cells were detected by bone marrow aspiration. Upper gastrointestinal endoscopy disclosed a protuberant lesion with a central ulcer on the greater curvature of the (Fig. 1). A biopsy sample was diagnosed pathohistologically as non- Hodgkin's lymphoma, diffuse, medium and large cell type. Computed tomography demonstrated a large mass measuring 12x9x10 cm with irregular inner contents. It had an indistinct border with the gastric wall showing an invasion into the anterior abdominal wall (Fig. 2). The patient was given combination (CHOP) chemotherapy from May 16, This included 374 Jpn J Clin Oncol 26(5) 1996

2 ATL WITH A GIANT GASTRIC TUMOR On the 30th postoperative day, additional chemotherapy (CHOP) was administered. Three days later, on August 28, the patient suddenly deteriorated and fell into a coma due to hypercalcemia with a serum calcium level of 16.1 mg/dl. Thereafter she developed acute renal failure and died due to respiratory failure on September 8, Neither abnormal lymphocytes nor leukocytosis were detected in the peripheral blood throughout the course. At autopsy, a swollen lymph node was found at the root of the superior mesenteric artery, but no other tumor growth was detected. Fig. 1. An endoscopic photograph showing a protuberant lesion with a large ulcer at the greater curvature of the. A biopsy sample was diagnosed histopathologically as non-hodgkin's lymphoma consisting of diffuse, medium and large cells. Fig. 2. Computed tomography demonstrated a large mass measuring 12 x 9 x 10 cm with irregular inner contents and an indistinct border with the gastric wall. The tumor also invades the anterior abdominal wall. Fig. 3. The resected specimen measured 14xl2x 13.5 cm. A cut section of the tumor shows a heterogeneous appearance with partial necrosis, forming a large ulcer inside the (arrow) mg of adriamycin, 800 mg of cyclophosphamide, 1.75 mg of vincristine, and 500 mg of prednisolone. Since the size of the tumor calculated by computed tomography showed a reduction of up to 40% after the first cycle of CHOP, a second cycle was administered from June 12. Though a temporary reduction was also seen on day 20 of the second cycle of chemotherapy, the tumor thereafter regrew, and had reached its former size by the time the patient underwent surgery six weeks later. After recovery from myelosuppression, surgery was performed on July 25. At laparotomy, the tumor was found to occupy the upper half of the abdomen, growing out of the, and had invaded the omentum, mesenterium, transverse colon, small intestine and anterior abdominal wall, forming a bulky mass. However, the liver, spleen, and distant nodes were not involved. A distal partial gastrectomy, with partial resection of the transverse colon, small intestine, and abdominal wall, was performed, but a curative operation could not be achieved. The resected specimen measured 14x12x13.5 cm (Fig. 3). Although extragastric invasion to the small intestine and transverse colon was apparent, the mucosa appeared to be macroscopically intact. A cross-section of the tumor revealed a heterogeneous appearance with partial necrosis, forming a large ulcer inside the. The border with the gastric wall was indistinct, suggesting a gastric wall origin. Histological examination of the resected specimen showed that the tumor was composed of medium-sized to large lymphoma cells massively infiltrating the submucosal layer of the (Fig. 4a). The shapes of the nuclei were irregular, some demonstrating notch formation (Fig. 4b). The tumor was diagnosed histologically as diffuse lymphoma, medium and large cell type. A phenotypic analysis of the lymphoma cells by flow cytometry showed a CD1", C D 2 +, CD3 +, C D 4 +, CD5 +, CD7 +, CD8 +, CD10", CD13", CD14", CD19", CD20", CD33" and HLA-DR + phenotype.

3 HIROYASU ET AL. (b) Fig. 4. Histological examination of the resected specimen showed that the lymphoma cells infiltrated massively into the submucosal layer of the (a). The tumor was composed of medium-sized to large lymphoma cells with irregularly shaped nuclei (b). Discussion Evidence of monoclonal integration of HTLV-I provirus into tumor cells by southern blotting is an important aid for diagnosis of ATL.8) Although we were unable to perform this test in the present case because frozen sections were not available, the histological appearance, the surface markers of the lymphoma cells, and the results of serological examination were all compatible with ATL.9) These findings were further confirmed by an elevated LDH level and hypercalcemia, which are more common in ATL than in other lymphomas.6' Based on the diagnostic criteria for ATL established by Shimoyama, this tumor was classified as lymphoma-type ATL (no lymphocytosis, 1% or fewer abnormal T-lymphocytes, and histologically proven lymphadenopathy with or without extranodal lesions).9) In comparison with other types of peripheral Tcell lymphoma, ATL is known to have less gastrointestinal involvement.6' In a study by Tsuzuki, a total of only 42 cases of ATL with gastric lesions were reported between 1980 and 1991 in Japan, most of them being ulcerative, erosive, or invasive, but not mass-forming.7* With regard to exophytic tumor formation in the, only two such cases have been reported to date, including this case and a case reported by Tsuzuki.7' However, Tsuzuki's patient had been initially treated for stage IV ATL one year prior to detection of the gastric tumor, and therefore this was not a primary gastric lymphoma. In another study, Dawson et al. indicated five major symptoms as criteria for primary malignant lymphoma of the intestinal tract: no su- perficial lymphadenopathy palpable, no enlarged mediastinal lymph nodes evident in chest radiographs, normal total and differential WBC counts, bowel lesions predominant at laparotomy, and no tumor in the liver or spleen.10' Consequently, the present case met all these criteria. The incidence of primary extranodal lymphoma in ATL is known to be as low as 4.6%.'" To our knowledge, only three cases of ATL originating primarily in the abdominal cavity have been reported to date. One case, reported by Nishimura et al., formed a large mass originating in the mesentery.12' The remaining two cases described by Kubonishi et al.li) and Shimamoto et o/.14) were of gastric origin, but not mass-forming. The present case is thus considered to be the first reported case of primary gastric ATL showing exophytic mass formation but no leukemic manifestation. The four previous cases of ATL originating primarily in the abdominal cavity are summarized in Table I. All three cases of gastric origin were in women. Interestingly, the two cases involving large mass-forming tumors did not respond to chemotherapy and also had a poor prognosis. The present case was also associated with other unique features. For instance, the patient had a past history of strongyloidiasis. Nakada et al. demonstrated that Strongyloides carriers have a 3-fold higher risk of HTLV antibody positivity than healthy controls.15' This is an important issue in the Okinawa islands, the southernmost subtropical islands of Japan, where both ATL and strongyloidiasis are endemic. Nakada stated that host immunosuppression in pre-atl or smoldering ATL permits the proliferation of parasites, thus leading Jpn J Clin Oncol 26(5) 1996 (a)

4 ATL WITH A GIANT GASTRIC TUMOR Table I. Primary Abdominal ATL Tumors Author Kubonishi et al. Shimamoto et al. Nishimura et al. Hiroyasu et al. Patient age, sex 41, Female 69, Female 64, Male 52, Female Origin mesentery to a high incidence of HTLV antibody positivity in parasite carriers. 1 * He also mentioned that parasite infection might also promote the growth of HTLV, but this hypothesis has yet to be proved. The phenotype of this tumor was also found to be unique. Most lymphoma cells in ATL have been reported to show a CD4 + CD8" phenotype. 17 ' The present case showed a CD4 + CD8 + phenotype, which has only been reported in 14% of all ATL cases. 18 ' Tamura et al. reported that co-expression of the surface antigens CD4 and CD8 may be a sign of disease aggressiveness and thus of poor prognosis, although the mechanisms for this remain unclear. 19 ' This case had other associated factors which could also have resulted in the poor prognosis, namely hypercalcemia and a high LDH level. 20) Hypercalcemia in ATL is reported to be caused by increased production of parathyroid hormone-related protein (PTHrP) in lymphoma cells. 2 " In this case, the additional chemotherapy may have caused sudden destruction of the tumor cells which had regrown within one month after surgery, resulting in excessive release of PTHrP. Among peripheral T-cell lymphomas, the prognosis of ATL is known to be extremely poor. 22 ' Furthermore, among the four subtypes of ATL, the prognosis of the lymphoma type is only slightly better than that of the acute type." Likewise in this case, chemotherapy was ineffective, probably because the tumor was too large, resulting in rapid tumor growth between the chemotherapy cycles. In addition, curative surgical resection could not be performed. In conclusion, we have experienced a rare case of lymphoma-type ATL forming a large abdominal tumor and showing no leukemic manifestations. Since the prognosis of lymphoma-type ATL is extremely poor in comparison with other lymphomas, we should bear in mind that ATL can form a protruding primary gastric tumor without leukemic manifestations. Mass Abnormal cells in formation peripheral blood (-) 4% of WBC counts (- ) none (at the time of surgery) ( + ) none (at the time of surgery) (+ ) none (throughout the course) References Survival >9 mo >7 mo 3 mo 4 mo 1) Takatsuki K, Uchiyama T, Sagawa K, Yodoi J: Adult T-cell leukaemia in Japan. In Seno S, Takaku F, Irino S, eds, Topics in Haematology, Exerpta MedicalO), Amsterdam-Oxford. p73-77, ) Uchiyama T, Yodoi J, Sagawa K, Takatsuki K, Uchino H: Adult T-cell leukemia: clinical and hematologic features of 16 cases. Blood 50: , ) The T- and B-cell malignancy study group: Statistical analysis of clinicopathological, virological and epidemiological data on lymphoid malignancies with special reference to Adult T-cell leukemia/lymphoma: a report of the second nationwide study of Japan. Jpn J Clin Oncol 15: , ) Shimoyama M: Recent progress in non-hodgkin's lymphoma study in Japan. Gan To Kagaku Ryoho 15: , 1988 (in Japanese) 5) Tobinai K: Recent progress in the chemotherapy of malignant lymphoma. Gan To Kagaku Ryoho 22: 437_443, 1995 (in Japanese) 6) Shimoyama M: Treatment of patients with adult T- cell leukemia-lymphoma: an overview. Gann Monograph on Cancer Res 39: 43-56, ) Tsuzuki H, Ohashi D, Iritani I, Kishimoto H, Ogawa H, Nakamura Y, Oda M: A resected case of Adult T-cell leukemia/lymphoma with a mass lesion in the. Nippon Rinshogekaigakkai Zasshi 53: , 1992 (in Japanese) 8) Yamaguchi K, Seiki M, Yoshida M, Nishimura H, Kawano F, Takatsuki K: The detection of human T- cell leukemia virus proviral DNA and its application for classification and diagnosis of T cell malignancy. Blood 63: , ) Shimoyama M: Diagnostic criteria and classification of clinical subtypes of adult T-cell leukaemialymphoma: a report from the Lymphoma Study Group ( ). Br J Haematol 79: , ) Dawson IM, Cornes JS, Morson BC: Primary malignant lymphoid tumors of the intestinal tract: report of 37 cases with a study of factors influencing prognosis. Br J Surg 49: 80-89, ) Shimamoto Y, Yamaguchi M: HTLV-I induced extranodal lymphomas. Leuk Lymphoma 7: 37-45,

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