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Colonic involvement by adult T-cell leukemia/lymphoma mimicking ulcerative colitis

2003; Elsevier BV; Volume: 58; Issue: 5 Linguagem: Inglês

10.1016/s0016-5107(03)02111-4

1097-6779

Hajime Isomoto, Hisashi Furusu, Yasunori Onizuka, Yasuhisa Kawaguchi, Yohei Mizuta, Takahiro Maeda, Shigeru Kohno,

Cutaneous lymphoproliferative disorders research

The GI tract is the most common site of extranodal lymphoma, and colorectal lymphoma comprises between 10% and 20% of primary gut lymphomas.1.Loehr W.J. Mujahed Z. Zahn F.D. Gray G.F. Thombiarson B. Primary lymphoma of the gastrointestinal tract: a review of 100 cases.Ann Surg. 1969; 170: 232-238Crossref PubMed Scopus (226) Google Scholar Of the latter, diffuse lymphomatosis of the colorectum accounts for only a small proportion, but it can have a unique appearance, mimicking inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn's disease.2.Friedman H.B. Silver G.M. Brown C.H. Lymphoma of the colon simulating ulcerative colitis. Report of four cases.Am J Dig Dis. 1968; 13: 910-917Crossref PubMed Scopus (39) Google Scholar, 3.Parnes I.H. Warner R.R. Berman R. Sanders M. Diffuse lymphosarcoma of the colon simulating ulcerative colitis.Mt Sinai J Med. 1974; 41: 802-806PubMed Google Scholar, 4.Wagonfeld J.B. Baker A.L. Reed J.S. Platz C.E. Kirsner J.B. Acute dilatation of the colon in malignant lymphoma.Gastroenterology. 1976; 70: 264-267PubMed Scopus (8) Google Scholar, 5.Weir A.B. Poon M.C. Groarke J.F. Wilkerson J.A. Lymphoma simulating Crohn's colitis.Dig Dis Sci. 1980; 25: 69-72Crossref PubMed Scopus (23) Google Scholar, 6.Sagar S. Selby P. Sloane J. McElwain T.J. Colorectal lymphoma simulating inflammatory colitis and diagnosed by immunohistochemistry.Postgrad Med J. 1986; 62: 51-53Crossref PubMed Scopus (12) Google Scholar, 7.Berkelhammer C. Hakim B. Chilis T. Hopkins W. Stein R. Port J. Spontaneous multiperforation in lymphomatous colitis masquerading as Crohn's disease.J Clin Gastroenterol. 1994; 19: 135-138Crossref PubMed Scopus (4) Google Scholar, 8.Hirakawa K. Fuchigami T. Nakamura S. Daimaru Y. Ohshima K. Sakai Y. et al.Primary gastrointestinal T-cell lymphoma resembling multiple lymphomatous polyposis.Gastroenterology. 1996; 111: 778-782Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar, 9.Son H.J. Rhee P.L. Kim J.J. Koh K.C. Paik S.W. Rhee J.C. et al.Primary T-cell lymphoma of the colon.Korean J Intern Med. 1997; 12: 238-241PubMed Google Scholar It has, thus, been termed lymphomatous colitis.8.Hirakawa K. Fuchigami T. Nakamura S. Daimaru Y. Ohshima K. Sakai Y. et al.Primary gastrointestinal T-cell lymphoma resembling multiple lymphomatous polyposis.Gastroenterology. 1996; 111: 778-782Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar Only a few cases of lymphomatous colitis mimicking IBD have been reported.2.Friedman H.B. Silver G.M. Brown C.H. Lymphoma of the colon simulating ulcerative colitis. Report of four cases.Am J Dig Dis. 1968; 13: 910-917Crossref PubMed Scopus (39) Google Scholar, 3.Parnes I.H. Warner R.R. Berman R. Sanders M. Diffuse lymphosarcoma of the colon simulating ulcerative colitis.Mt Sinai J Med. 1974; 41: 802-806PubMed Google Scholar, 4.Wagonfeld J.B. Baker A.L. Reed J.S. Platz C.E. Kirsner J.B. Acute dilatation of the colon in malignant lymphoma.Gastroenterology. 1976; 70: 264-267PubMed Scopus (8) Google Scholar, 5.Weir A.B. Poon M.C. Groarke J.F. Wilkerson J.A. Lymphoma simulating Crohn's colitis.Dig Dis Sci. 1980; 25: 69-72Crossref PubMed Scopus (23) Google Scholar, 6.Sagar S. Selby P. Sloane J. McElwain T.J. Colorectal lymphoma simulating inflammatory colitis and diagnosed by immunohistochemistry.Postgrad Med J. 1986; 62: 51-53Crossref PubMed Scopus (12) Google Scholar, 7.Berkelhammer C. Hakim B. Chilis T. Hopkins W. Stein R. Port J. Spontaneous multiperforation in lymphomatous colitis masquerading as Crohn's disease.J Clin Gastroenterol. 1994; 19: 135-138Crossref PubMed Scopus (4) Google Scholar, 8.Hirakawa K. Fuchigami T. Nakamura S. Daimaru Y. Ohshima K. Sakai Y. et al.Primary gastrointestinal T-cell lymphoma resembling multiple lymphomatous polyposis.Gastroenterology. 1996; 111: 778-782Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar, 9.Son H.J. Rhee P.L. Kim J.J. Koh K.C. Paik S.W. Rhee J.C. et al.Primary T-cell lymphoma of the colon.Korean J Intern Med. 1997; 12: 238-241PubMed Google Scholar Adult T-cell leukemia/lymphoma (ATLL) is an aggressive and usually fatal T-cell malignancy caused by human T-lymphotropic virus type 1 (HTLV-1).10.Uchiyama T. Yodoi J. Sagawa K. Takatsuki K. Uchino H. Adult T cell leukemia: clinical and hematological features of 16 cases.Blood. 1977; 50: 481-492Crossref PubMed Google Scholar Adult T-cell leukemia/lymphoma is characterized by a marked tendency for neoplastic cell invasion into various organs, including the liver, the spleen, and the skin.11.Utsunomiya A. Hanada S. Clinical and pathological features of gastrointestinal lesions in patients with adult T-cell leukemia.Nihon Monaikei Gakkai Kaishi. 1990; 30 ([in Japanese]): 408-418Google Scholar, 12.Sato E. Hasui K. Tokunaga M. Autopsy findings of adult T-cell leukemia/lymphoma.Gann Monogr Cancer Res. 1982; 28: 51-64Google Scholar GI involvement in patients with ATLL also is frequent; the percentage of patients with ATLL cell infiltration into the large intestine is no less than 17.9%.11.Utsunomiya A. Hanada S. Clinical and pathological features of gastrointestinal lesions in patients with adult T-cell leukemia.Nihon Monaikei Gakkai Kaishi. 1990; 30 ([in Japanese]): 408-418Google Scholar To our knowledge, however, there has been no documentation of lymphomatous colitis in patients with ATLL. This is the first report of a case of ATLL with colonic involvement mimicking UC. A 47-year-old man was hospitalized because of a 2-week history of frequent diarrhea, bloody stool, and upper and lower abdominal pain. The family history included pancreatic cancer (father). The patient had been treated with an antihypertensive medication. Examination revealed bilateral cervical, axillary, and inguinal lymph node enlargement; hepatosplenomegaly was not present. Multiple eruptions were present on the skin of the anterior chest wall and back. The white blood cell count was 5200/mm3 (normal: 3000-9000/mm3) with 5% abnormal lymphocytes. Serum concentrations of lactate dehydrogenase and calcium were, respectively, 535 mU/mL (202-435 mU/mL) and 8.5 mg/dL (8.5-11.5 mg/dL). Serum anti–HTLV-1 antibody was positive. CT demonstrated enlargement of retroperitoneal, paragastric, and splenic hilar lymph nodes. An inguinal lymph node biopsy specimen revealed diffuse infiltration by abnormal lymphocytes, and monoclonal integration of HTLV-1 provirus in chromosomal DNA was demonstrated.13.Isomoto H. Ohnita K. Haraguchi M. Mizuta Y. Momita S. Ikeda S. et al.Jejunal perforation in a patient with adult T-cell leukemia.Leuk Lymphoma. 2001; 42: 1423-1427Crossref PubMed Scopus (5) Google Scholar The abnormal lymphocytes were larger than red blood cells (diameter 15-20 μm) and contained highly indented, multilobulated nuclei with condensed chromatin and scant, agranular, and basophilic cytoplasm, consistent with the morphologic characteristics of ATLL cells.10.Uchiyama T. Yodoi J. Sagawa K. Takatsuki K. Uchino H. Adult T cell leukemia: clinical and hematological features of 16 cases.Blood. 1977; 50: 481-492Crossref PubMed Google Scholar, 14.Shimamoto Y. Suga K. Shibata K. Matsunaga M. Yano H. Yamaguchi M. Clinical importance of extraordinary integration patterns of human T-cell lymphotropic virus type 1 proviral DNA in adult T-cell leukemia/lymphoma.Blood. 1994; 84: 853-858PubMed Google Scholar Flow cytometry showed the following surface phenotypes for these cells: CD3, 86.0%; CD4, 89.7%; CD8, 10.7%; and HLA-DR, 73.4%. A skin biopsy specimen also revealed a similar neoplastic cell infiltration into the dermal layer. A bone marrow biopsy specimen was unremarkable. Stool cultures, ova and parasites, and Clostridium difficile toxin were negative. Serum enzyme-linked immunosorbent assay for Entamoeba histolytica and cytomegalovirus pp65 antigenemia test were negative. At upper endoscopy, multiple protruding masses covered by a normal-appearing mucosa or with ulceration were present in the proximal body of the stomach (Fig. 1A). Colonoscopy demonstrated changes closely resembling those of UC throughout the colorectum, including a granular, friable, and hyperemic mucosa that bled on contact (Fig. 1B) and multiple superficial ulcers. In biopsy specimens from the gastric and colonic lesions, there was a diffuse proliferation of abnormal cells resembling those found in the lymph nodes (Fig. 2A). Immunohistochemical analysis revealed that these abnormal cells were negative for B-cell (CD20 and CD79a) but positive for T-cell markers (CD3 and UCHL-1; Fig. 2B). No areas of crypt abscess, granuloma, or other lesions suggestive of IBD could be found microscopically. Neither infectious agents themselves nor their characteristic pathologic findings were identified in the histopathologic sections. There were no abnormal findings on a double-contrast radiograph of the small intestine.Figure 1A, Endoscopic view showing multiple protruding masses with ulceration in proximal body of stomach. B, Colonoscopic view showing granular, friable, and hyperemic mucosa with superficial ulcers.View Large Image Figure ViewerDownload (PPT)Figure 2A, Photomicrograph of biopsy specimen from colonic lesion showing proliferation of abnormal lymphocytes with hyperchromatic and highly convoluted nuclei (H&E, orig. mag.×400). B, Photomicrograph showing that the abnormal cells stain positive for anti–UCHL-1 antibody (a universal T-cell marker) (H&E, orig. mag.×400).View Large Image Figure ViewerDownload (PPT)Figure 2A, Photomicrograph of biopsy specimen from colonic lesion showing proliferation of abnormal lymphocytes with hyperchromatic and highly convoluted nuclei (H&E, orig. mag.×400). B, Photomicrograph showing that the abnormal cells stain positive for anti–UCHL-1 antibody (a universal T-cell marker) (H&E, orig. mag.×400).View Large Image Figure ViewerDownload (PPT) Based on the diagnostic criteria and classification of clinical subtypes of ATLL of the Lymphoma Study Group in Japan,15.Shimoyama M. Diagnostic criteria and classification of clinical subtypes of adult T-cell leukemia-lymphoma, a report from the Lymphoma Study Group (1984-1987).Br J Haematol. 1991; 79: 428-437Crossref PubMed Scopus (1270) Google Scholar a final diagnosis was made of lymphoma, subtype ATLL with gastric invasion and colonic involvement simulating UC. The patient was treated with combination chemotherapy (vincristine, cyclophosphamide, adriamycin, prednisolone). Three courses led to the disappearance of the superficial and intra-abdominal lymph node enlargement and the skin eruptions. Endoscopy 4 months later demonstrated resolution of the gastric and colorectal lesions. However, 8 months after initiation of chemotherapy, extensive skin eruptions and generalized bulky lymphadenopathy recurred, and the condition of the patient worsened gradually despite chemotherapy. The patient died 12 months after commencement of treatment. Autopsy was refused. Colonic involvement by ATLL presents as thickened mucosal folds with erosions, polypoid masses, nodules with ulceration, diffuse petechiae, and mucosal edema and granularity.16.Utsunomiya A. Hanada S. Terada A. Kodama M. Uematsu T. Tsukasa S. et al.Adult T-cell leukemia with leukemia cell infiltration into the gastrointestinal tract.Cancer. 1988; 61: 824-828Crossref PubMed Scopus (52) Google Scholar Extensive ATLL involvement of the colorectum occasionally appears as myriad polypoid lesions similar to multiple lymphomatous polyposis.17.Itsuno M. Makiyama K. Muta K. Furukawa K. Hara K. Tabata S. et al.Adult T-cell leukemia with multiple lymphomatous polyposis of the gastrointestinal tract.Endoscopy. 1995; 27: 700-703Crossref PubMed Scopus (15) Google Scholar However, a careful search of the MEDLINE database from 1966 to 2001 did not retrieve any report of ATLL with lymphomatous colitis that simulated IBD. Thus, the present case seems to be the first reported of ATLL with UC-like involvement of the colorectum. The reason for such variability in the gross appearance remains unclear, but the manner of neoplastic cell infiltration and growth, as well as the degree of infiltration, might explain these differences.18.Isomoto H. Ohnita K. Mizuta Y. Maeda T. Onizuka Y. Miyazaki M. et al.Clinical and endoscopic features of adult T-cell leukemia/lymphoma with duodenal involvement.J Clin Gastroenterol. 2001; 33: 241-246Crossref PubMed Scopus (15) Google Scholar When malignant lymphoma of the colon appears as multiple tumors or diffuse involvement, i.e., lymphomatous colitis, it may be difficult to distinguish from IBD, especially UC, because both disorders can have similar symptomatology and gross findings.2.Friedman H.B. Silver G.M. Brown C.H. Lymphoma of the colon simulating ulcerative colitis. Report of four cases.Am J Dig Dis. 1968; 13: 910-917Crossref PubMed Scopus (39) Google Scholar, 3.Parnes I.H. Warner R.R. Berman R. Sanders M. Diffuse lymphosarcoma of the colon simulating ulcerative colitis.Mt Sinai J Med. 1974; 41: 802-806PubMed Google Scholar, 4.Wagonfeld J.B. Baker A.L. Reed J.S. Platz C.E. Kirsner J.B. Acute dilatation of the colon in malignant lymphoma.Gastroenterology. 1976; 70: 264-267PubMed Scopus (8) Google Scholar, 5.Weir A.B. Poon M.C. Groarke J.F. Wilkerson J.A. Lymphoma simulating Crohn's colitis.Dig Dis Sci. 1980; 25: 69-72Crossref PubMed Scopus (23) Google Scholar Friedman et al.2.Friedman H.B. Silver G.M. Brown C.H. Lymphoma of the colon simulating ulcerative colitis. Report of four cases.Am J Dig Dis. 1968; 13: 910-917Crossref PubMed Scopus (39) Google Scholar reported 4 cases and reviewed 11 others in which they felt lymphoma of the colon was misdiagnosed as UC, in one case for as long as 15 years. Colonic lymphoma simulating Crohn's disease has been described, albeit less frequently. One such patient was treated for 6 months with corticosteroid enemas until lymphadenopathy revealed the true nature of the disease; the patient developed toxic megacolon secondary to poorly differentiated lymphocytic lymphoma and died.4.Wagonfeld J.B. Baker A.L. Reed J.S. Platz C.E. Kirsner J.B. Acute dilatation of the colon in malignant lymphoma.Gastroenterology. 1976; 70: 264-267PubMed Scopus (8) Google Scholar Although it is possible that our patient developed ATLL coincidentally, there was no histopathologic evidence of crypt abscess, granuloma, or other lesions suggestive of IBD. The short time lapse between initial symptoms and definite ATLL, and the relatively rapid response to chemotherapy make the possibility of IBD unlikely. In addition, associated lesions were present in the lymph nodes, the stomach, and the skin. Such diffuse lymphadenopathy is never seen in idiopathic UC, although there are a few cases reported of angiofollicular lymph node hyperplasia concomitant with UC.19.Shimamoto C. Takao Y. Hirata I. Ohshiba S. Kimura's disease (angiolymphoid hyperplasia with eosinophilia) associated with ulcerative colitis.Gastroenterol Jpn. 1993; 28: 298-303PubMed Google Scholar, 20.Browne D. Barton E.N. Barrow K.O. Williams N.P. Hanchard B. Multicentric angiofollicular lymph node hyperplasia in ulcerative colitis. A case report.West Indian Med J. 1996; 45: 34-36PubMed Google Scholar The histopathologic differentiation of ATLL from UC also may be problematic, especially if available biopsy specimens are small. As UC becomes chronic, the leukocytic infiltration becomes a nonspecific mononuclear infiltration because of the predominance of lymphocytes.2.Friedman H.B. Silver G.M. Brown C.H. Lymphoma of the colon simulating ulcerative colitis. Report of four cases.Am J Dig Dis. 1968; 13: 910-917Crossref PubMed Scopus (39) Google Scholar, 5.Weir A.B. Poon M.C. Groarke J.F. Wilkerson J.A. Lymphoma simulating Crohn's colitis.Dig Dis Sci. 1980; 25: 69-72Crossref PubMed Scopus (23) Google Scholar The histopathologic pattern in malignant lymphoma often consists of infiltration of round cells, usually of the same degree of maturity, that morphologically closely resemble the mononuclear cell pattern seen in UC.2.Friedman H.B. Silver G.M. Brown C.H. Lymphoma of the colon simulating ulcerative colitis. Report of four cases.Am J Dig Dis. 1968; 13: 910-917Crossref PubMed Scopus (39) Google Scholar, 5.Weir A.B. Poon M.C. Groarke J.F. Wilkerson J.A. Lymphoma simulating Crohn's colitis.Dig Dis Sci. 1980; 25: 69-72Crossref PubMed Scopus (23) Google Scholar In such cases, immunohistologic studies demonstrating monoclonal proliferation of lymphocytes are helpful in discriminating between lymphoma and IBD,6.Sagar S. Selby P. Sloane J. McElwain T.J. Colorectal lymphoma simulating inflammatory colitis and diagnosed by immunohistochemistry.Postgrad Med J. 1986; 62: 51-53Crossref PubMed Scopus (12) Google Scholar, 9.Son H.J. Rhee P.L. Kim J.J. Koh K.C. Paik S.W. Rhee J.C. et al.Primary T-cell lymphoma of the colon.Korean J Intern Med. 1997; 12: 238-241PubMed Google Scholar and also elucidate cellular origin.21.Ruskone-Fourmestraux A. Delmer A. Lavergne A. Molina T. Brousse N. Audouin J. et al.Multiple lymphomatous polyposis of the gastrointestinal tract: prospective clinicopathologic study of 31 cases. Groupe D'etude des Lymphomes Digestifs.Gastroenterology. 1997; 112: 7-16Abstract Full Text PDF PubMed Scopus (140) Google Scholar Most often, tumor cells in colonic lymphoma are derived from B-cells, as shown by monocytoid expression of B-cell markers, including CD20 and CD79a.8.Hirakawa K. Fuchigami T. Nakamura S. Daimaru Y. Ohshima K. Sakai Y. et al.Primary gastrointestinal T-cell lymphoma resembling multiple lymphomatous polyposis.Gastroenterology. 1996; 111: 778-782Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar, 21.Ruskone-Fourmestraux A. Delmer A. Lavergne A. Molina T. Brousse N. Audouin J. et al.Multiple lymphomatous polyposis of the gastrointestinal tract: prospective clinicopathologic study of 31 cases. Groupe D'etude des Lymphomes Digestifs.Gastroenterology. 1997; 112: 7-16Abstract Full Text PDF PubMed Scopus (140) Google Scholar However, there are several documented cases of T-cell–derived primary colonic lymphoma simulating IBD.8.Hirakawa K. Fuchigami T. Nakamura S. Daimaru Y. Ohshima K. Sakai Y. et al.Primary gastrointestinal T-cell lymphoma resembling multiple lymphomatous polyposis.Gastroenterology. 1996; 111: 778-782Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar, 9.Son H.J. Rhee P.L. Kim J.J. Koh K.C. Paik S.W. Rhee J.C. et al.Primary T-cell lymphoma of the colon.Korean J Intern Med. 1997; 12: 238-241PubMed Google Scholar In our patient, abnormal lymphocytes proliferating in the colonic mucosa, with the morphologic characteristics of the ATLL cells in the lymph node biopsy specimen, were immunohistochemically positive for T-cell markers (CD3 and UCHL-1) but not B-cell markers, indicating that the affected lesions were of T-cell lineage. It is well known that HTLV-1 infection is endemic in Japan.13.Isomoto H. Ohnita K. Haraguchi M. Mizuta Y. Momita S. Ikeda S. et al.Jejunal perforation in a patient with adult T-cell leukemia.Leuk Lymphoma. 2001; 42: 1423-1427Crossref PubMed Scopus (5) Google Scholar Thus, clinicians and pathologists must be aware that lymphomatous colitis masquerading as IBD also can originate from T-cells, without HTLV-1 infection, albeit the condition is exceptional. The increased risk of colorectal cancer among patients with IBD is well established.22.Lewis J.D. Deren J.J. Lichtenstein G.R. Cancer risk in patients with inflammatory bowel disease.Gastroenterol Clin North Am. 1999; 28: 459-477Abstract Full Text Full Text PDF PubMed Scopus (130) Google Scholar However, studies of a possible link between lymphoma and IBD have provided conflicting results.23.Greenstein A.J. Gennuso R. Sachar D.B. Helmann T. Smith H. Janowitz H.D. et al.Extraintestinal cancers in inflammatory bowel disease.Cancer. 1985; 56: 1914-1921Crossref Scopus (193) Google Scholar, 24.Palli D.P. Trallori G. Bagnori S. Saieva C. Tarantino O. Ceroti M. et al.Hodgkin's disease risk in increased in patients with ulcerative colitis.Gastroenterology. 2000; 119: 647-653Abstract Full Text Full Text PDF PubMed Scopus (118) Google Scholar, 25.Lewis J.D. Bilker W.B. Brensinger C. Deren J.J. Vaughn D.J. Strom B.L. Inflammatory bowel disease is not associated with an increased risk of lymphoma.Gastroenterology. 2001; 121: 1080-1087Abstract Full Text Full Text PDF PubMed Scopus (280) Google Scholar Some investigators have suggested that patients with IBD may be at increased risk for lymphoma.22.Lewis J.D. Deren J.J. Lichtenstein G.R. Cancer risk in patients with inflammatory bowel disease.Gastroenterol Clin North Am. 1999; 28: 459-477Abstract Full Text Full Text PDF PubMed Scopus (130) Google Scholar, 23.Greenstein A.J. Gennuso R. Sachar D.B. Helmann T. Smith H. Janowitz H.D. et al.Extraintestinal cancers in inflammatory bowel disease.Cancer. 1985; 56: 1914-1921Crossref Scopus (193) Google Scholar In contrast, a population-based study failed to identify an increase in the risk of lymphoma among patients with IBD.25.Lewis J.D. Bilker W.B. Brensinger C. Deren J.J. Vaughn D.J. Strom B.L. Inflammatory bowel disease is not associated with an increased risk of lymphoma.Gastroenterology. 2001; 121: 1080-1087Abstract Full Text Full Text PDF PubMed Scopus (280) Google Scholar To definitively answer this question, larger studies of newly identified cases are needed.25.Lewis J.D. Bilker W.B. Brensinger C. Deren J.J. Vaughn D.J. Strom B.L. Inflammatory bowel disease is not associated with an increased risk of lymphoma.Gastroenterology. 2001; 121: 1080-1087Abstract Full Text Full Text PDF PubMed Scopus (280) Google Scholar In conclusion, a case of ATLL with lymphomatous colitis simulating UC is presented. This condition appears to be extremely rare, but its recognition may be of importance for clinicians and pathologists, especially in Japan. We thank Kunihiko Murase, PhD, MD, for his contribution in the preparation of histopathologic slides.