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Mantle cell lymphoma of the colon with massive splenomegaly: A case report
Arab Journal of Gastroenterology 12 (2011) 162–165
Contents lists available at SciVerse ScienceDirect
Arab Journal of Gastroenterology journal homepage: www.elsevier.com/locate/ajg
Case Report
Mantle cell lymphoma of the colon with massive splenomegaly: A case report Ahmed Alomair a, Ibrahim Masoodi a,⇑, Mussa A Faggeeh b a b
Department of Gastroenterology, King Fahad Medical City, Riyadh, Saudi Arabia Department of Pathology, King Fahad Medical City, Riyadh, Saudi Arabia
a r t i c l e
i n f o
Article history: Received 23 May 2010 Accepted 8 January 2011
Keywords: Mantle cell lymphoma Colonic tumour
a b s t r a c t We describe colonoscopic features in a 77-year-old female with relapse of mantle cell lymphoma, who presented with a history of rectal bleeding of 2 months’ duration. Her initial colonoscopy 3 years prior to the current presentation had revealed no gross lesions of mantle cell lymphoma; however, there was evidence of microscopic disease at that time as well. The patient had now developed classical lesions following relapse of the disease. The present case report gives the natural history of this rare tumour. The comparative colonoscopic features with a brief review of mantle cell lymphoma are presented. Ó 2011 Arab Journal of Gastroenterology. Published by Elsevier B.V. All rights reserved.
Introduction Primary gastrointestinal (GI) involvement of mantle cell lymphoma (MCL) is rare with a frequency reported between 4% and 9% of all GI B-cell non-Hodgkin’s lymphomas [1]. MCL, earlier addressed as ‘multiple lymphomatous polyposis’ (MLP), often presents with multiple lymphomatous polyps involving several digestive tract segments and a marked tendency towards extraintestinal spread. During the past decade, MCL has been established as a new disease entity. The normal counterparts of the cells forming this malignant lymphoma are found in the mantle zone of the lymph node, a thin layer surrounding the germinal follicles. These cells have small- to medium-sized nuclei, are commonly indented or cleaved and stain positively with CD5, CD20, cyclin D1 and FMC7 antibodies; this lymphoma was initially thought to be an indolent tumour, but its natural course was not thoroughly investigated until the 1990s, when the B-cell lymphoma 1 (BCL1) oncogene was identified as a marker for this disease. MCL belongs to the so-called peripheral (differentiated) B-cell non-Hodgkin’s lymphomas. It runs an aggressive course; there is quick progression and most cases are diagnosed in the advanced stages. The most frequent endoscopic finding of MCL is lymphomatous polyposis. Usually, long segments of the GI tract are involved as in the index case. Case report A 77-year-old female initially presented to a local hospital in November 2005 with a history of left hypochondriac dragging sensation of 4 months’ duration associated with low-grade fever. Examination at that time revealed moderate splenomegaly. Bone⇑ Corresponding author. Tel.: +966 545481266. E-mail address: [email protected] (I. Masoodi).
marrow biopsy revealed poorly demarcated aggregates of atypical lymphocytes varying in size, and immunohistochemical studies showed positive CD20 and BCL-2. She received six cycles of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP)based chemotherapy. She however relapsed after a few months and again developed progressive splenomegaly. Computed tomography (CT) scan of the abdomen revealed huge splenomegaly, measuring at least 30 cm craniocaudal showing multiple wedgeshaped low-attenuation areas suggestive of a differential of multiple splenic infarcts versus lymphomatous infiltration. The huge spleen had displaced the small- and large-bowel loops to the contralateral side. It had also displaced the left kidney posteriorly. The liver and other viscera were normal. She underwent an oesophagogastroduodenoscopy (OGD) and a colonoscopic examination, which revealed some nodularity at the pylorus (Fig. 1), and colonoscopy showed oedematous mucosa at the transverse colon, the descending colon and the caecum. No other abnormality was seen (Figs. 2 and 3). Biopsy revealed MCL. The patient underwent splenectomy in January 2008 because of the features of hypersplenism and fear of bleeding even with minor trauma. Haematoxylin and eosin (H&E) sections showed extensive involvement of white pulp and red pulp by monomorphic small atypical lymphocytes with an area of infarction. In addition, the sections also revealed lymph node involved by the same neoplastic process. Flow cytometry performed on the spleen demonstrated lymphoma cells positive for CD45, CD19,CD20, CD5, human leucocyte antigen- DR-1 (HLADR) and lambda restricted and negative for CD23. The patient received rituximab 375 mg m 2 for four cycles. Bortezomib 1.3 mg m 2 on days 1, 4, 8 and 11 and rituximab were used as maintenance. After a few months, she relapsed at the right side of the neck and presented with a right neck mass 4 5 cm and a right tonsillar mass. She was given external beam radiotherapy; she received 50 Gy in 25 fractions. She tolerated the treatment well
1687-1979/$ - see front matter Ó 2011 Arab Journal of Gastroenterology. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.ajg.2011.01.008
A. Alomair et al. / Arab Journal of Gastroenterology 12 (2011) 162–165
163
without any unacceptable side effects. In December 2009, she presented with recurrent rectal bleeding of 2 months’ duration. On examination, she was haemodynamically stable with mild hepatomegaly. On evaluation, she had a haemoglobin level of 11 gm dl 1
and normal liver and renal function tests. Colonoscopy revealed multiple mass lesions at various sites in the rectum, sigmoid colon, descending colon and caecum as shown in Figs. 4–7. There were no synchronous lesions seen on upper GI endoscopy. The colonic
Fig. 1. OGD in 2006 showing the gastric antrum.
Fig. 4. Colonoscopy in 2009: Polypoidal lesions in rectum.
Fig. 2. Colonoscopy in 2006: No gross lesions in the descending colon.
Fig. 5. Colonoscopy in 2009: Polypoidal lesions in descending colon.
Fig. 3. Colonoscopy in 2006: No gross lesions in the transverse colon.
Fig. 6. Colonoscopy in 2009: Polypoidal lesions in sigmoid colon.
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A. Alomair et al. / Arab Journal of Gastroenterology 12 (2011) 162–165
Fig. 10. MCL: The lymphocytes are strongly positive for CD2 (10). Fig. 7. Colonoscopy in 2009: Polypoidal lesions in caecum.
Fig. 8. Monotonous population of lymphocytes arranged in sheet (Haematoxylin and Eosin, 10).
Fig. 9. MCL: The lymphocytes are positive for Cyclin D (immunochemistry, 20).
biopsy (Figs. 8–10) was suggestive of non-Hodgkin’s B-cell lymphoma consistent with MCL.
Discussion Extranodal lymphomas commonly occur in the GI tract. They account for 2% of primary GI tract lymphomas [2]. Non-Hodgkin’s
lymphoma of the colon is rare and, consequently, is a poorly studied extranodal lymphoma [3]. MCL is a discrete entity, unrelated to small lymphocytic or small-cleaved-cell lymphomas [4]. Abdominal pain is the most common symptom and obstruction is unusual; however, reports of intussusception [5] are known. Invariably, patients have diffuse involvement of the GI tract; the index case had microscopic involvement initially and 3 years later developed diffuse large classical polypoidal lesions. Bleeding per rectum mimicking ulcerative colitis is known. Robert et al. [6] described colonic lymphoma masquerading as ulcerative colitis in a 71year-old female who had superficial biopsy typical of ulcerative colitis. The authors postulated that an indolent lymphoid proliferation must have been the underlying disease. Chung et al. [7] described a series of seven cases of MCL over a period of 6 years. The majority of patients in their series were elderly as in the index case and six out of seven cases had multiple polypoidal lesions ranging from 0.1 to 4 cm with central ulcerations. Diffuse polyposis was seen uniformly in their series and polyposis was predominant in the rectum, ascending colon, rather than other sections in the colon. We could not intubate the ileum due to a large polypoid lesion in the ileocaecal area (Fig. 7), but, in their series, the ileum was usually involved by polyposis. Bowel-wall thickening or mass formation developed exclusively in the ascending colon, rectum or ileum. Splenomegaly has been frequently observed in these patients. Our patient had massive splenomegaly reaching up to pelvis with infarcts and underwent elective splenectomy for fear of bleeding and spontaneous rupture. To the best of our knowledge, this is the first report where MCL was associated with huge splenomegaly. There are reports where MCL has been simultaneously seen with adenocarcinoma colon; [8] in rare cases, it can even present with skin lesions [9]. The differential diagnosis of MCL includes small B-cell lymphoma, lymphoplasmacytic lymphoma, nodal, extranodal and splenic marginal zone lymphomas and follicular small cleaved cell lymphoma. In most instances, these disorders can be distinguished from one another by morphology, distinctive immunophenotypic profiles and genetic features [10]. MCL exhibits considerable molecular heterogeneity and complexity and is regarded as one of the most challenging lymphomas to treat. There is no accepted standard therapy; however, one controlled clinical trial demonstrated that intensive induction immunochemotherapy followed by high-dose radio chemotherapy and autologous stem cell transplantation was superior to conventional treatment [11]. The clinical evolution is relatively aggressive with poor response to conventional therapeutic regimens and a median survival duration of 3–4 years. Further studies are needed to define better new therapeutic strategies for the management of these
A. Alomair et al. / Arab Journal of Gastroenterology 12 (2011) 162–165
patients [11]. Earlier diagnosis with further studies integrating novel agents are still required to determine the optimal treatment with less toxicity. Many new agents (i.e., the Food and Drug Administration (FDA)-approved MCL indication of bortezomib, temsirolimus, thalidomide, etc.) are or should be available for refractory or relapsed patients. In conclusion, our case of MCL represents GI involvement with massive splenomegaly necessitating elective splenectomy and an uneven path in the management of this not-so-common disease. This case also reflects the natural history of development of polyposis. The patient initially had no gross lesions on endoscopy but later developed classical lesions, emphasising the need for a high index of suspicion in a particular case. Conflicts of interest The authors declared that there was no conflict of interest. References [1] Bairey O, Ruchlemer R, Shpilberg O. Non-Hodgkin’s lymphomas of the colon. Isr Med Assoc J 2006;8(12):832–5.
165
[2] Meral M, Demirpençe M, Gönen C, et al. Diffuse gastrointestinal involvement of mantle cell lymphoma. Turk J Gastroenterol 2008;19(2):117–20. [3] Salar A, Juanpere N, Bellosillo B, et al. Gastrointestinal involvement in mantle cell lymphoma: a prospective clinic, endoscopic, and pathologic study. Am J Surg Pathol 2006;30(10):1274–80. [4] Barista I, Romaguera JE, Cabanillas F. Mantle-cell lymphoma. Lancet Oncol 2001;2(3):141–8. [5] Kella VKN, Constantine R, Parikh NS, et al. Mantle cell lymphoma of the gastrointestinal tract presenting with multiple intussusceptions – case report and review of literature. World J Surg Oncol 2009;7:Art. No. 60. [6] Robert ME, Kuo FC, Longtine JA, et al. Diffuse colonic mantle cell lymphoma in a patient with presumed ulcerative colitis: detection of a precursor monoclonal lymphoid population using polymerase chain reaction and immunohistochemistry. Am J Surg Pathol 1996;20(8):1024–31. [7] Chung HH, Kim YH, Kim JH, et al. Imaging findings of mantle cell lymphoma involving gastrointestinal tract. Yonsei Med J 2003;44(1):49–57. [8] Padmanabhan V, Trainer TD. Synchronous adenocarcinoma and mantle cell lymphoma of the colon. Arch Pathol Lab Med 2003;127(2):E64–66. [9] Motegi SI, Okada E, Nagai Y, et al. Skin manifestation of mantle cell lymphoma. Eur J Dermatol 2006;16(4):435–8. [10] Kurtin PJ. Mantle cell lymphoma. Adv Anat Pathol 1998;5(6):376–98. [11] Campo E, Raffeld M, Jaffe ES. Mantle-cell lymphoma. Semin Hematol 1999;36(2):115–27.
Contents lists available at SciVerse ScienceDirect
Arab Journal of Gastroenterology journal homepage: www.elsevier.com/locate/ajg
Case Report
Mantle cell lymphoma of the colon with massive splenomegaly: A case report Ahmed Alomair a, Ibrahim Masoodi a,⇑, Mussa A Faggeeh b a b
Department of Gastroenterology, King Fahad Medical City, Riyadh, Saudi Arabia Department of Pathology, King Fahad Medical City, Riyadh, Saudi Arabia
a r t i c l e
i n f o
Article history: Received 23 May 2010 Accepted 8 January 2011
Keywords: Mantle cell lymphoma Colonic tumour
a b s t r a c t We describe colonoscopic features in a 77-year-old female with relapse of mantle cell lymphoma, who presented with a history of rectal bleeding of 2 months’ duration. Her initial colonoscopy 3 years prior to the current presentation had revealed no gross lesions of mantle cell lymphoma; however, there was evidence of microscopic disease at that time as well. The patient had now developed classical lesions following relapse of the disease. The present case report gives the natural history of this rare tumour. The comparative colonoscopic features with a brief review of mantle cell lymphoma are presented. Ó 2011 Arab Journal of Gastroenterology. Published by Elsevier B.V. All rights reserved.
Introduction Primary gastrointestinal (GI) involvement of mantle cell lymphoma (MCL) is rare with a frequency reported between 4% and 9% of all GI B-cell non-Hodgkin’s lymphomas [1]. MCL, earlier addressed as ‘multiple lymphomatous polyposis’ (MLP), often presents with multiple lymphomatous polyps involving several digestive tract segments and a marked tendency towards extraintestinal spread. During the past decade, MCL has been established as a new disease entity. The normal counterparts of the cells forming this malignant lymphoma are found in the mantle zone of the lymph node, a thin layer surrounding the germinal follicles. These cells have small- to medium-sized nuclei, are commonly indented or cleaved and stain positively with CD5, CD20, cyclin D1 and FMC7 antibodies; this lymphoma was initially thought to be an indolent tumour, but its natural course was not thoroughly investigated until the 1990s, when the B-cell lymphoma 1 (BCL1) oncogene was identified as a marker for this disease. MCL belongs to the so-called peripheral (differentiated) B-cell non-Hodgkin’s lymphomas. It runs an aggressive course; there is quick progression and most cases are diagnosed in the advanced stages. The most frequent endoscopic finding of MCL is lymphomatous polyposis. Usually, long segments of the GI tract are involved as in the index case. Case report A 77-year-old female initially presented to a local hospital in November 2005 with a history of left hypochondriac dragging sensation of 4 months’ duration associated with low-grade fever. Examination at that time revealed moderate splenomegaly. Bone⇑ Corresponding author. Tel.: +966 545481266. E-mail address: [email protected] (I. Masoodi).
marrow biopsy revealed poorly demarcated aggregates of atypical lymphocytes varying in size, and immunohistochemical studies showed positive CD20 and BCL-2. She received six cycles of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP)based chemotherapy. She however relapsed after a few months and again developed progressive splenomegaly. Computed tomography (CT) scan of the abdomen revealed huge splenomegaly, measuring at least 30 cm craniocaudal showing multiple wedgeshaped low-attenuation areas suggestive of a differential of multiple splenic infarcts versus lymphomatous infiltration. The huge spleen had displaced the small- and large-bowel loops to the contralateral side. It had also displaced the left kidney posteriorly. The liver and other viscera were normal. She underwent an oesophagogastroduodenoscopy (OGD) and a colonoscopic examination, which revealed some nodularity at the pylorus (Fig. 1), and colonoscopy showed oedematous mucosa at the transverse colon, the descending colon and the caecum. No other abnormality was seen (Figs. 2 and 3). Biopsy revealed MCL. The patient underwent splenectomy in January 2008 because of the features of hypersplenism and fear of bleeding even with minor trauma. Haematoxylin and eosin (H&E) sections showed extensive involvement of white pulp and red pulp by monomorphic small atypical lymphocytes with an area of infarction. In addition, the sections also revealed lymph node involved by the same neoplastic process. Flow cytometry performed on the spleen demonstrated lymphoma cells positive for CD45, CD19,CD20, CD5, human leucocyte antigen- DR-1 (HLADR) and lambda restricted and negative for CD23. The patient received rituximab 375 mg m 2 for four cycles. Bortezomib 1.3 mg m 2 on days 1, 4, 8 and 11 and rituximab were used as maintenance. After a few months, she relapsed at the right side of the neck and presented with a right neck mass 4 5 cm and a right tonsillar mass. She was given external beam radiotherapy; she received 50 Gy in 25 fractions. She tolerated the treatment well
1687-1979/$ - see front matter Ó 2011 Arab Journal of Gastroenterology. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.ajg.2011.01.008
A. Alomair et al. / Arab Journal of Gastroenterology 12 (2011) 162–165
163
without any unacceptable side effects. In December 2009, she presented with recurrent rectal bleeding of 2 months’ duration. On examination, she was haemodynamically stable with mild hepatomegaly. On evaluation, she had a haemoglobin level of 11 gm dl 1
and normal liver and renal function tests. Colonoscopy revealed multiple mass lesions at various sites in the rectum, sigmoid colon, descending colon and caecum as shown in Figs. 4–7. There were no synchronous lesions seen on upper GI endoscopy. The colonic
Fig. 1. OGD in 2006 showing the gastric antrum.
Fig. 4. Colonoscopy in 2009: Polypoidal lesions in rectum.
Fig. 2. Colonoscopy in 2006: No gross lesions in the descending colon.
Fig. 5. Colonoscopy in 2009: Polypoidal lesions in descending colon.
Fig. 3. Colonoscopy in 2006: No gross lesions in the transverse colon.
Fig. 6. Colonoscopy in 2009: Polypoidal lesions in sigmoid colon.
164
A. Alomair et al. / Arab Journal of Gastroenterology 12 (2011) 162–165
Fig. 10. MCL: The lymphocytes are strongly positive for CD2 (10). Fig. 7. Colonoscopy in 2009: Polypoidal lesions in caecum.
Fig. 8. Monotonous population of lymphocytes arranged in sheet (Haematoxylin and Eosin, 10).
Fig. 9. MCL: The lymphocytes are positive for Cyclin D (immunochemistry, 20).
biopsy (Figs. 8–10) was suggestive of non-Hodgkin’s B-cell lymphoma consistent with MCL.
Discussion Extranodal lymphomas commonly occur in the GI tract. They account for 2% of primary GI tract lymphomas [2]. Non-Hodgkin’s
lymphoma of the colon is rare and, consequently, is a poorly studied extranodal lymphoma [3]. MCL is a discrete entity, unrelated to small lymphocytic or small-cleaved-cell lymphomas [4]. Abdominal pain is the most common symptom and obstruction is unusual; however, reports of intussusception [5] are known. Invariably, patients have diffuse involvement of the GI tract; the index case had microscopic involvement initially and 3 years later developed diffuse large classical polypoidal lesions. Bleeding per rectum mimicking ulcerative colitis is known. Robert et al. [6] described colonic lymphoma masquerading as ulcerative colitis in a 71year-old female who had superficial biopsy typical of ulcerative colitis. The authors postulated that an indolent lymphoid proliferation must have been the underlying disease. Chung et al. [7] described a series of seven cases of MCL over a period of 6 years. The majority of patients in their series were elderly as in the index case and six out of seven cases had multiple polypoidal lesions ranging from 0.1 to 4 cm with central ulcerations. Diffuse polyposis was seen uniformly in their series and polyposis was predominant in the rectum, ascending colon, rather than other sections in the colon. We could not intubate the ileum due to a large polypoid lesion in the ileocaecal area (Fig. 7), but, in their series, the ileum was usually involved by polyposis. Bowel-wall thickening or mass formation developed exclusively in the ascending colon, rectum or ileum. Splenomegaly has been frequently observed in these patients. Our patient had massive splenomegaly reaching up to pelvis with infarcts and underwent elective splenectomy for fear of bleeding and spontaneous rupture. To the best of our knowledge, this is the first report where MCL was associated with huge splenomegaly. There are reports where MCL has been simultaneously seen with adenocarcinoma colon; [8] in rare cases, it can even present with skin lesions [9]. The differential diagnosis of MCL includes small B-cell lymphoma, lymphoplasmacytic lymphoma, nodal, extranodal and splenic marginal zone lymphomas and follicular small cleaved cell lymphoma. In most instances, these disorders can be distinguished from one another by morphology, distinctive immunophenotypic profiles and genetic features [10]. MCL exhibits considerable molecular heterogeneity and complexity and is regarded as one of the most challenging lymphomas to treat. There is no accepted standard therapy; however, one controlled clinical trial demonstrated that intensive induction immunochemotherapy followed by high-dose radio chemotherapy and autologous stem cell transplantation was superior to conventional treatment [11]. The clinical evolution is relatively aggressive with poor response to conventional therapeutic regimens and a median survival duration of 3–4 years. Further studies are needed to define better new therapeutic strategies for the management of these
A. Alomair et al. / Arab Journal of Gastroenterology 12 (2011) 162–165
patients [11]. Earlier diagnosis with further studies integrating novel agents are still required to determine the optimal treatment with less toxicity. Many new agents (i.e., the Food and Drug Administration (FDA)-approved MCL indication of bortezomib, temsirolimus, thalidomide, etc.) are or should be available for refractory or relapsed patients. In conclusion, our case of MCL represents GI involvement with massive splenomegaly necessitating elective splenectomy and an uneven path in the management of this not-so-common disease. This case also reflects the natural history of development of polyposis. The patient initially had no gross lesions on endoscopy but later developed classical lesions, emphasising the need for a high index of suspicion in a particular case. Conflicts of interest The authors declared that there was no conflict of interest. References [1] Bairey O, Ruchlemer R, Shpilberg O. Non-Hodgkin’s lymphomas of the colon. Isr Med Assoc J 2006;8(12):832–5.
165
[2] Meral M, Demirpençe M, Gönen C, et al. Diffuse gastrointestinal involvement of mantle cell lymphoma. Turk J Gastroenterol 2008;19(2):117–20. [3] Salar A, Juanpere N, Bellosillo B, et al. Gastrointestinal involvement in mantle cell lymphoma: a prospective clinic, endoscopic, and pathologic study. Am J Surg Pathol 2006;30(10):1274–80. [4] Barista I, Romaguera JE, Cabanillas F. Mantle-cell lymphoma. Lancet Oncol 2001;2(3):141–8. [5] Kella VKN, Constantine R, Parikh NS, et al. Mantle cell lymphoma of the gastrointestinal tract presenting with multiple intussusceptions – case report and review of literature. World J Surg Oncol 2009;7:Art. No. 60. [6] Robert ME, Kuo FC, Longtine JA, et al. Diffuse colonic mantle cell lymphoma in a patient with presumed ulcerative colitis: detection of a precursor monoclonal lymphoid population using polymerase chain reaction and immunohistochemistry. Am J Surg Pathol 1996;20(8):1024–31. [7] Chung HH, Kim YH, Kim JH, et al. Imaging findings of mantle cell lymphoma involving gastrointestinal tract. Yonsei Med J 2003;44(1):49–57. [8] Padmanabhan V, Trainer TD. Synchronous adenocarcinoma and mantle cell lymphoma of the colon. Arch Pathol Lab Med 2003;127(2):E64–66. [9] Motegi SI, Okada E, Nagai Y, et al. Skin manifestation of mantle cell lymphoma. Eur J Dermatol 2006;16(4):435–8. [10] Kurtin PJ. Mantle cell lymphoma. Adv Anat Pathol 1998;5(6):376–98. [11] Campo E, Raffeld M, Jaffe ES. Mantle-cell lymphoma. Semin Hematol 1999;36(2):115–27.