267
0 1992
The Japanese Society of
Pathology
Jejunal Perforation Associated with Cytomega lovirus Inf ection in a Patient with Adult T-cell Leukemia-Lymphoma
Kazuki Nabeshima', Ei Sakaguch?, Shohei lnoue2, Yoshito Eizuru3, Yoichi Minamishima3, and Masashi Koono'
A patient with adult T-cell leukemia-lymphoma suffered a jejunal perforation, which we believe was directly attributable to cytomegalovirus (CMV) infection. I n the areas of ulceration and perforation in the small bowel, blood vessels penetrating the muscularis propria showed extensive lining of cytomegalic endothelial cells with CMV inclusions, accompanied by occasional disruption of the walls, partial occlusion of the lumina, fibrin thrombi, and hemorrhage. The CMV-induced vascular damage seemed to be closely related to the occurrence of ulcers and perforation. The recognition of CMV as a cause of lethal gastrointestinal lesions i n immunocompromised hosts has become more important with the advent of anti-CMV therapy. Acta Pathol Jpn 42 : 267 -271, 1992.
Key words : Cytomegalovirus infection, Jejunal perforation, Adult T-cell leukemia-lymphoma
In the immunocompromised host, cytornegalovirus (CMV) infection is a major cause of morbidity and mortality (1). Pneumonia is the most frequently recognized form of overt CMV infection, while the gastrointestinal tract is a less common site of CMV infection(2). So far intestinal perforation associated with CMV infection has been described on rare occasions(3). Most perforations occurred in patients with acquired immune deficiency syndrome (AIDS) (1, 3-8) and only in a few cases in patients with other immunodeficiencies (7, 9, 10). We describe herein a n autopsy case of jejunal perforation in a patient with adult T-cell leukemiaReceived August 21, 1991. Accepted for publication November 25, 1991. '2nd Department of Pathology, ZDepartmentof Dermatology, 3Department of Microbiology, Miyazaki Medical College, Miyazaki. Mailing address : Masashi Koono, 2nd Department of Pathology, Miyazaki Medical College, 5200 Kihara, Kiyotake, Miyazaki-gun, Miyazaki 889-1 6, Japan.
lymphoma (ATLL), and postulate the possible contribution of CMV in the perforation. In light of new medical therapy including ganciclovir (1I), it is important to diagnose C MV-rela ted gastrointestinal lesions early enough to institute effective treatment.
CLINICAL SUMMARY A 34-year-old male was admitted to Miyazaki Medical College Hospital because of generalized papulonecrotic lesions, edema, and generalized lymphadenopathy. Three months earlier, he first noticed papules on his thighs and had anorexia and fatigue; by one week before admission the papules became generalized. On admission hepatosplenomegaly was present. Laboratory studies showed a high LDH level (2,312 lU/l), mild hypercalcemia (10.6 mg/dl), and the presence of flower-like atypical lymphoid cells in peripheral blood (Fig. 1). Antibodies to human T lymphotropic virus type I (HTLV-I) was positive ( ~ 1 0 , 2 4 0 ) . Skin biopsy revealed malignant lymphoma, diffuse pleomorphic type. He was diagnosed as adult T-cell leukemia (ATL) and
Figure 1. Leukemic lymphocytes in peripheral blood. Giem-
sa.
268
CMV-related Jejunal Perforation in ATLL (Nabeshima et a/.)
Figure 2. a : A large, well-defined ulcer with a perforation in the jejunum. b : A well-defined and short-circular ulcer ( U l - I V ) in ileum. c : A low-power photomicrograph from area of jejunal perforation. HE. d : A U 1 I V ulcer with overhanging edges. HE. In c and d, blood vessels lined by cytomegalic endothelial cells are seen in proximity to the ulcers (arrowhead). Small nodular infiltration of ATL cells is present in the submucosa (arrow).
Acta Pathologica Japonica 4 2 (4) : 1 9 9 2
269
Figure 3. a : Penetrating blood vessels within the necrotic muscularis propria a t the ulcer edge show cytomegalic endothelial cells with intranuclear inclusions characteristic of CMV infection. HE. b : lmmunohistochemically, the cytomegalic endothelial cells are positive for CMV antigen. c : The muscularis propria adjacent to the area of ulceration shows inflammatory cell infiltration, destruction of muscle and inclusion bodies in smooth muscle cells. HE. d : lmrnunoperoxidase staining for CMV antigen reveals positive staining of inclusions in smooth muscle cells.
2 70
CMV-related Jejunal Perforation in ATLL (Nabeshima ef a/.)
treated with courses of VEPA and M-FEPA therapy. Skin lesions, hepatomegaly and an elevated LDH level showed partial improvement. Three months after admission, however, he had a loss of appetite followed by a sudden onset of intermittent epigastralgia and soon frank signs of peritonitis developed. Thereafter his circulatory status rapidly deteriorated to shock condition and he died on August 17, 1990. The overall duration of the last gastrointestinal episode was five days.
PATHOLOGICAL FINDINGS A t autopsy, the peritoneal cavity showed fecal peritonitis. There were ten ulcers in the jejunum and ileum. Two of them in the jejunum 1 2 0 c m and 1 5 0 c m distal from Treitz's ligament had perforated (Fig. 2a). They measured 2 and 0.5 cm in diameter, respectively. The other ulcers, ranging from U1-II to IV, were well-defined, short and circular with the long axis parallel to Kerckring's folds of the intestine (Fig. 2b). Mesenteric and para-aortic lymph nodes were enlarged, but there was no tumoral lesion of lymphoma in the gastrointestinal tract. Microscopically, the ulcer bases and edges consisted of granulation tissue with acute and chronic inflammation (Figs. 2c, d). Many intranuclear and intracytoplasmic inclusions typical of CMV were found in the endothelial cells throughout the submucosa, the muscularis propria and the subserosa in the tissue immediately surrounding the area of ulceration and perforation. In particular the penetrating blood vessels within the involved muscularis propria frequently showed lining of cytomegalic endothelial cells with focal disruption of the walls and small areas of associated hemorrhage (Fig. 3a). The cytomegalic endothelial cells frequently protruded into the vascular lumen and the lumen was stenotic with occasional fibrin thrombi, while adjacent vessels without CMV inclusions were patent. The involved blood vessels were mainly venules and small veins with sizes ranging from 10 to 70 p m in diameter. The smooth muscle cells in the ulcer bed also contained CMV inclusions (Fig. 3c), while no epithelial cell of the jejunal and ileal mucosa contained them. lmmunohistochemically, anti-CMV antibody (C23) (12) demonstrated the presence of CMV antigen in cytomegalic endothelial cells and smooth muscle cells (Figs. 3b, d). In the colon there was no ulcerative lesion, but blood vessels in the mucosa and the submucosa frequently showed cytomegalic endothelial cells. CMV infection also involved the lungs, adrenal glands and the skin. The skin showed ulcerative lesions w i t h cytomegalic endothelial cells at the ulcer beds and edges. In the small intestine, ATL cells infiltrated the mucosa in a scattered manner or formed small nodules in the submucosa. Some of the nodules were found in the
vicinity of ulcers, but not at the edges of them. Enlarged lymph nodes showed feature of the diffuse pleomorphic type of non-Hodgkin's lymphoma. There was no islet cell tumor of the pancreas that could cause Zollinger-E lliso n syndrome.
DISCUSSION CMV-related gastrointestinal perforation has never been reported in ATLL and the case reported here seems to be the first. After histopathological examination of this case, vascular damage caused by CMV infection seemed to be the major cause of the jejunal perforation. Furthermore, although both primary and secondary CMV infections seemed to be present in the digestive tract, only the latter was involved in the process of ulceration and perforation. As for the pathogenesis of CMV-induced focal bowel perforation, viral-induced vasculitis (3, 6, 13), viral-inor viral induced destruction of muscularis propria (l), duced enteritis(4) are all thought to be important. In our case, numerous cytomegalic endothelial cells with CMV inclusions were present in association with vascular damage along the penetrating venules and veins in muscularis propria of the areas of ulceration and perforation. As it is suggested that local spread of CMV occurs via endothelial cell infection (14), it is likely that in this case CMV spread via venous blood flow, from the mucosa to the muscularis propria. Thus, the resulting impairment of local circulation, which leads to the destruction of muscle coat, appears to be most important for the development of deep ulcers and perforation. It still remains unclear why the spread of CMV occurred only in the small bowel but not in the colon. Since ATL cell infiltration was seen predominantly in the small bowel, it might have caused endothelial cells to become vulnerable to CMV infection. Concerning the development of CMV infection in the digestive tract, some argue that CMV is merely a secondary invader into previously damaged intestinal tissue (2), while others postulate that a primary CMV infection can occur in intestinal t i s s u e ( l 3 15). In our case, CMV infection in colonic tissue seemed to be primary and latent because cytomegalic endothelial cells with CMV inclusions were present in the normal-appearing colonic mucosa and submucosa. On the other hand, CMV infection in the small bowel seemed to be a secondary superinfection in areas of preexisting inflammation because it was found only in areas of ulceration and perforation. In the present case, ATL cells infiltrated the mucosa and the submucosa of the small bowel. Since ATL cells are known to cause mucosal injury(l6), it is likely that infiltrating ATL cells caused a primary mucosal injury,
Acta Pathologica Japonica 42 (4) : 1992
which was followed by CMV infection t o cause further tissue damage leading t o the development of ulceration and perforation. ATLL is the most common type of leukemialymphoma in the southern part of Kyushu (17, 18). When treating ATLL patients we should be aware of CMV infection as one o f the pathogens causing acute abdominal crises such as massive hemorrhage o r visceral perforation. This recognition has become more important because of the availability of the anti-CMV agent, ganciclovir (1 I), which may prevent fatal intestinal perforation of the type reported here. In the present case, CMV infection was found not only in the small bowel but also in the skin and colonic and rectal mucosa which are known as the most common sites f o r CMV infection in the digestive tract (1). Since the small bowel is a difficult site to examine for CMV infection, if CMV infection is found in the rectal o r colonic mucosa by biopsy, the presence of CMV-related lesions in the small bowel should be considered. Acknowledgements : The authors thank Mr. Shinya Sato for his skillful technical assistance in immunohistochemistry, and Mr. Takashi Miyamoto for photographic assistance.
REFERENCES 1. Fernandes B, Brunton J, and Koven 1. Ileal perforation due to cytomegaloviral enteritis. Can J Surg 2 9 : 453-456, 1986. 2. Rosen P, Armstrong D, and Rice N. Gastrointestinal cytomegalovirus infection. Arch Intern Med 132 : 274-276, 1973. 3. Tatum E l , Sun PCJ, and Cohn DL. Cytomegalovirus vasculitis and colon perforation in a patient with the acquired immunodeficiency syndrome. Pathology 21 : 235-238, 1989. 4. Frank D and Raicht RF. Intestinal perforation associated with cytomegalovirus infection in patients with acquired immune deficiency syndrome. Am J Gastroenterol 79: 201--205, 1984. 5. Tucker RM, Swanson S, and Wenzel RP. Cytomegalovirus and appendiceal perforation in a patient with acquired immunodeficiency syndrome.
2 71
South Med J 8 2 : 1056-1057, 1989.
6. Burke G, Nichols L, Balogh K, et a/. Perforation of the
7. 8.
9. 10.
11.
12.
13. 14.
15.
16.
17.
18.
terminal ileum with cytomegalovirus vasculitis and Kaposi’s sarcoma in a patient with acquired immunodeficiency syndrome. Surgery 102 : 540-545, 1987. lwasaki T. Alimentary tract lesions in cytomegalovirus infection. Acta Pathol Jpn 3 7 : 549-565, 1987. Kram HB, Hino ST, Cohen RE, DeSantis SA, and Shoemaker WC. Spontaneous colonic perforation secondary to cytomegalovirus in a patient with acquired immune deficiency syndrome. Crit Care Med 1 2 : 469-471, 1984. Henson D. Cytomegalovirus inclusion bodies in the gastrointestinal tract. Arch Pathol 9 3 : 477-482, 1972. Goodman ZD, Boitnott JK, and Yardley JH. Perforation of the colon associated with cytomegalovirus infection. Dig Dis Sci 2 4 : 376-380, 1979. Collaborative DHPG Treatment Study Group. Treatment of serous cytomegalovirus infections with 9-( 1, 3-dihydroxy-2-propoxymethyl) guanine in patients with AIDS and other immunodeficiencies. N Engl J Med 314: 801-805, 1986. Masuho Y, Matsumoto Y, Sugano T, Fujinaga S, and Minamishima Y. Human monoclonal antibodies neutralizing human cytomegalovirus. J Gen Virol 6 8 : 1457-1461, 1987. Foucar E, Mukai K, Foucar K, Sutherland DER, and van Buren CT. Colon ulceration in lethal cytomegalovirus infection. Am J Clin Pathol 7 6 : 788-801, 1981. Myerson D, Hackman RC, Nelson JA, Ward DC, and McDougall JK. Widespread presence of histologically occult cytomegalovirus. Hum Pathol 15 : 430-439, 1984. Roche JK, Cheung K-S, Boldogh I, Huang E-S, and Lang DJ. Cytomegalovirus : Detection in human colonic and circulating mononuclear cells in association with gastrointestinal disease. Int J Cancer 27 : 659667, 1981. Utsunomiya A and Hanada S. Characteristics of gastrointestinal lesions in ATL. Nippon Mounaikei Gakkai Kaishi 30: 135, 1990 (in Japanese). Matsumoto M, Nomura K, Matsumoto 1,et a/. Adult T-cell leukemia-lymphoma in Kagoshima district, southwestern Japan : Clinical and hematological characteristics. Jpn J Clin Oncol 9: 325-336, 1979. Suzumiya J, Sumiyoshi A, Tamura K, et a/. Malignant lymphoma in the Miyazaki district : Analysis of 237 biopsy cases. Jpn J Clin Oncol 1 5 : 35-47, 1985.
0 1992
The Japanese Society of
Pathology
Jejunal Perforation Associated with Cytomega lovirus Inf ection in a Patient with Adult T-cell Leukemia-Lymphoma
Kazuki Nabeshima', Ei Sakaguch?, Shohei lnoue2, Yoshito Eizuru3, Yoichi Minamishima3, and Masashi Koono'
A patient with adult T-cell leukemia-lymphoma suffered a jejunal perforation, which we believe was directly attributable to cytomegalovirus (CMV) infection. I n the areas of ulceration and perforation in the small bowel, blood vessels penetrating the muscularis propria showed extensive lining of cytomegalic endothelial cells with CMV inclusions, accompanied by occasional disruption of the walls, partial occlusion of the lumina, fibrin thrombi, and hemorrhage. The CMV-induced vascular damage seemed to be closely related to the occurrence of ulcers and perforation. The recognition of CMV as a cause of lethal gastrointestinal lesions i n immunocompromised hosts has become more important with the advent of anti-CMV therapy. Acta Pathol Jpn 42 : 267 -271, 1992.
Key words : Cytomegalovirus infection, Jejunal perforation, Adult T-cell leukemia-lymphoma
In the immunocompromised host, cytornegalovirus (CMV) infection is a major cause of morbidity and mortality (1). Pneumonia is the most frequently recognized form of overt CMV infection, while the gastrointestinal tract is a less common site of CMV infection(2). So far intestinal perforation associated with CMV infection has been described on rare occasions(3). Most perforations occurred in patients with acquired immune deficiency syndrome (AIDS) (1, 3-8) and only in a few cases in patients with other immunodeficiencies (7, 9, 10). We describe herein a n autopsy case of jejunal perforation in a patient with adult T-cell leukemiaReceived August 21, 1991. Accepted for publication November 25, 1991. '2nd Department of Pathology, ZDepartmentof Dermatology, 3Department of Microbiology, Miyazaki Medical College, Miyazaki. Mailing address : Masashi Koono, 2nd Department of Pathology, Miyazaki Medical College, 5200 Kihara, Kiyotake, Miyazaki-gun, Miyazaki 889-1 6, Japan.
lymphoma (ATLL), and postulate the possible contribution of CMV in the perforation. In light of new medical therapy including ganciclovir (1I), it is important to diagnose C MV-rela ted gastrointestinal lesions early enough to institute effective treatment.
CLINICAL SUMMARY A 34-year-old male was admitted to Miyazaki Medical College Hospital because of generalized papulonecrotic lesions, edema, and generalized lymphadenopathy. Three months earlier, he first noticed papules on his thighs and had anorexia and fatigue; by one week before admission the papules became generalized. On admission hepatosplenomegaly was present. Laboratory studies showed a high LDH level (2,312 lU/l), mild hypercalcemia (10.6 mg/dl), and the presence of flower-like atypical lymphoid cells in peripheral blood (Fig. 1). Antibodies to human T lymphotropic virus type I (HTLV-I) was positive ( ~ 1 0 , 2 4 0 ) . Skin biopsy revealed malignant lymphoma, diffuse pleomorphic type. He was diagnosed as adult T-cell leukemia (ATL) and
Figure 1. Leukemic lymphocytes in peripheral blood. Giem-
sa.
268
CMV-related Jejunal Perforation in ATLL (Nabeshima et a/.)
Figure 2. a : A large, well-defined ulcer with a perforation in the jejunum. b : A well-defined and short-circular ulcer ( U l - I V ) in ileum. c : A low-power photomicrograph from area of jejunal perforation. HE. d : A U 1 I V ulcer with overhanging edges. HE. In c and d, blood vessels lined by cytomegalic endothelial cells are seen in proximity to the ulcers (arrowhead). Small nodular infiltration of ATL cells is present in the submucosa (arrow).
Acta Pathologica Japonica 4 2 (4) : 1 9 9 2
269
Figure 3. a : Penetrating blood vessels within the necrotic muscularis propria a t the ulcer edge show cytomegalic endothelial cells with intranuclear inclusions characteristic of CMV infection. HE. b : lmmunohistochemically, the cytomegalic endothelial cells are positive for CMV antigen. c : The muscularis propria adjacent to the area of ulceration shows inflammatory cell infiltration, destruction of muscle and inclusion bodies in smooth muscle cells. HE. d : lmrnunoperoxidase staining for CMV antigen reveals positive staining of inclusions in smooth muscle cells.
2 70
CMV-related Jejunal Perforation in ATLL (Nabeshima ef a/.)
treated with courses of VEPA and M-FEPA therapy. Skin lesions, hepatomegaly and an elevated LDH level showed partial improvement. Three months after admission, however, he had a loss of appetite followed by a sudden onset of intermittent epigastralgia and soon frank signs of peritonitis developed. Thereafter his circulatory status rapidly deteriorated to shock condition and he died on August 17, 1990. The overall duration of the last gastrointestinal episode was five days.
PATHOLOGICAL FINDINGS A t autopsy, the peritoneal cavity showed fecal peritonitis. There were ten ulcers in the jejunum and ileum. Two of them in the jejunum 1 2 0 c m and 1 5 0 c m distal from Treitz's ligament had perforated (Fig. 2a). They measured 2 and 0.5 cm in diameter, respectively. The other ulcers, ranging from U1-II to IV, were well-defined, short and circular with the long axis parallel to Kerckring's folds of the intestine (Fig. 2b). Mesenteric and para-aortic lymph nodes were enlarged, but there was no tumoral lesion of lymphoma in the gastrointestinal tract. Microscopically, the ulcer bases and edges consisted of granulation tissue with acute and chronic inflammation (Figs. 2c, d). Many intranuclear and intracytoplasmic inclusions typical of CMV were found in the endothelial cells throughout the submucosa, the muscularis propria and the subserosa in the tissue immediately surrounding the area of ulceration and perforation. In particular the penetrating blood vessels within the involved muscularis propria frequently showed lining of cytomegalic endothelial cells with focal disruption of the walls and small areas of associated hemorrhage (Fig. 3a). The cytomegalic endothelial cells frequently protruded into the vascular lumen and the lumen was stenotic with occasional fibrin thrombi, while adjacent vessels without CMV inclusions were patent. The involved blood vessels were mainly venules and small veins with sizes ranging from 10 to 70 p m in diameter. The smooth muscle cells in the ulcer bed also contained CMV inclusions (Fig. 3c), while no epithelial cell of the jejunal and ileal mucosa contained them. lmmunohistochemically, anti-CMV antibody (C23) (12) demonstrated the presence of CMV antigen in cytomegalic endothelial cells and smooth muscle cells (Figs. 3b, d). In the colon there was no ulcerative lesion, but blood vessels in the mucosa and the submucosa frequently showed cytomegalic endothelial cells. CMV infection also involved the lungs, adrenal glands and the skin. The skin showed ulcerative lesions w i t h cytomegalic endothelial cells at the ulcer beds and edges. In the small intestine, ATL cells infiltrated the mucosa in a scattered manner or formed small nodules in the submucosa. Some of the nodules were found in the
vicinity of ulcers, but not at the edges of them. Enlarged lymph nodes showed feature of the diffuse pleomorphic type of non-Hodgkin's lymphoma. There was no islet cell tumor of the pancreas that could cause Zollinger-E lliso n syndrome.
DISCUSSION CMV-related gastrointestinal perforation has never been reported in ATLL and the case reported here seems to be the first. After histopathological examination of this case, vascular damage caused by CMV infection seemed to be the major cause of the jejunal perforation. Furthermore, although both primary and secondary CMV infections seemed to be present in the digestive tract, only the latter was involved in the process of ulceration and perforation. As for the pathogenesis of CMV-induced focal bowel perforation, viral-induced vasculitis (3, 6, 13), viral-inor viral induced destruction of muscularis propria (l), duced enteritis(4) are all thought to be important. In our case, numerous cytomegalic endothelial cells with CMV inclusions were present in association with vascular damage along the penetrating venules and veins in muscularis propria of the areas of ulceration and perforation. As it is suggested that local spread of CMV occurs via endothelial cell infection (14), it is likely that in this case CMV spread via venous blood flow, from the mucosa to the muscularis propria. Thus, the resulting impairment of local circulation, which leads to the destruction of muscle coat, appears to be most important for the development of deep ulcers and perforation. It still remains unclear why the spread of CMV occurred only in the small bowel but not in the colon. Since ATL cell infiltration was seen predominantly in the small bowel, it might have caused endothelial cells to become vulnerable to CMV infection. Concerning the development of CMV infection in the digestive tract, some argue that CMV is merely a secondary invader into previously damaged intestinal tissue (2), while others postulate that a primary CMV infection can occur in intestinal t i s s u e ( l 3 15). In our case, CMV infection in colonic tissue seemed to be primary and latent because cytomegalic endothelial cells with CMV inclusions were present in the normal-appearing colonic mucosa and submucosa. On the other hand, CMV infection in the small bowel seemed to be a secondary superinfection in areas of preexisting inflammation because it was found only in areas of ulceration and perforation. In the present case, ATL cells infiltrated the mucosa and the submucosa of the small bowel. Since ATL cells are known to cause mucosal injury(l6), it is likely that infiltrating ATL cells caused a primary mucosal injury,
Acta Pathologica Japonica 42 (4) : 1992
which was followed by CMV infection t o cause further tissue damage leading t o the development of ulceration and perforation. ATLL is the most common type of leukemialymphoma in the southern part of Kyushu (17, 18). When treating ATLL patients we should be aware of CMV infection as one o f the pathogens causing acute abdominal crises such as massive hemorrhage o r visceral perforation. This recognition has become more important because of the availability of the anti-CMV agent, ganciclovir (1 I), which may prevent fatal intestinal perforation of the type reported here. In the present case, CMV infection was found not only in the small bowel but also in the skin and colonic and rectal mucosa which are known as the most common sites f o r CMV infection in the digestive tract (1). Since the small bowel is a difficult site to examine for CMV infection, if CMV infection is found in the rectal o r colonic mucosa by biopsy, the presence of CMV-related lesions in the small bowel should be considered. Acknowledgements : The authors thank Mr. Shinya Sato for his skillful technical assistance in immunohistochemistry, and Mr. Takashi Miyamoto for photographic assistance.
REFERENCES 1. Fernandes B, Brunton J, and Koven 1. Ileal perforation due to cytomegaloviral enteritis. Can J Surg 2 9 : 453-456, 1986. 2. Rosen P, Armstrong D, and Rice N. Gastrointestinal cytomegalovirus infection. Arch Intern Med 132 : 274-276, 1973. 3. Tatum E l , Sun PCJ, and Cohn DL. Cytomegalovirus vasculitis and colon perforation in a patient with the acquired immunodeficiency syndrome. Pathology 21 : 235-238, 1989. 4. Frank D and Raicht RF. Intestinal perforation associated with cytomegalovirus infection in patients with acquired immune deficiency syndrome. Am J Gastroenterol 79: 201--205, 1984. 5. Tucker RM, Swanson S, and Wenzel RP. Cytomegalovirus and appendiceal perforation in a patient with acquired immunodeficiency syndrome.
2 71
South Med J 8 2 : 1056-1057, 1989.
6. Burke G, Nichols L, Balogh K, et a/. Perforation of the
7. 8.
9. 10.
11.
12.
13. 14.
15.
16.
17.
18.
terminal ileum with cytomegalovirus vasculitis and Kaposi’s sarcoma in a patient with acquired immunodeficiency syndrome. Surgery 102 : 540-545, 1987. lwasaki T. Alimentary tract lesions in cytomegalovirus infection. Acta Pathol Jpn 3 7 : 549-565, 1987. Kram HB, Hino ST, Cohen RE, DeSantis SA, and Shoemaker WC. Spontaneous colonic perforation secondary to cytomegalovirus in a patient with acquired immune deficiency syndrome. Crit Care Med 1 2 : 469-471, 1984. Henson D. Cytomegalovirus inclusion bodies in the gastrointestinal tract. Arch Pathol 9 3 : 477-482, 1972. Goodman ZD, Boitnott JK, and Yardley JH. Perforation of the colon associated with cytomegalovirus infection. Dig Dis Sci 2 4 : 376-380, 1979. Collaborative DHPG Treatment Study Group. Treatment of serous cytomegalovirus infections with 9-( 1, 3-dihydroxy-2-propoxymethyl) guanine in patients with AIDS and other immunodeficiencies. N Engl J Med 314: 801-805, 1986. Masuho Y, Matsumoto Y, Sugano T, Fujinaga S, and Minamishima Y. Human monoclonal antibodies neutralizing human cytomegalovirus. J Gen Virol 6 8 : 1457-1461, 1987. Foucar E, Mukai K, Foucar K, Sutherland DER, and van Buren CT. Colon ulceration in lethal cytomegalovirus infection. Am J Clin Pathol 7 6 : 788-801, 1981. Myerson D, Hackman RC, Nelson JA, Ward DC, and McDougall JK. Widespread presence of histologically occult cytomegalovirus. Hum Pathol 15 : 430-439, 1984. Roche JK, Cheung K-S, Boldogh I, Huang E-S, and Lang DJ. Cytomegalovirus : Detection in human colonic and circulating mononuclear cells in association with gastrointestinal disease. Int J Cancer 27 : 659667, 1981. Utsunomiya A and Hanada S. Characteristics of gastrointestinal lesions in ATL. Nippon Mounaikei Gakkai Kaishi 30: 135, 1990 (in Japanese). Matsumoto M, Nomura K, Matsumoto 1,et a/. Adult T-cell leukemia-lymphoma in Kagoshima district, southwestern Japan : Clinical and hematological characteristics. Jpn J Clin Oncol 9: 325-336, 1979. Suzumiya J, Sumiyoshi A, Tamura K, et a/. Malignant lymphoma in the Miyazaki district : Analysis of 237 biopsy cases. Jpn J Clin Oncol 1 5 : 35-47, 1985.
