- Email: [email protected]
Classical hodgkin lymphoma arising in the rectum
Annals of Diagnostic Pathology 9 (2005) 38 – 42
Case report
Classical hodgkin lymphoma arising in the rectumB Jose R. Valbuena, MDa, Gabriela Gualco, MDa, Ismael Espejo-Plascencia, MDa, L. Jeffrey Medeiros, MDb,T a
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX b Department of Pathology, Hospital Civil de Guadalajara, Guadalajara, Mexico
Abstract
We report a case of an 81-year-old immunocompetent Mexican man who underwent an abdominalperineal rectal resection for a mass clinically thought to be carcinoma. Histopathologic diagnosis revealed classical Hodgkin lymphoma, nodular sclerosis type, involving the rectum. The diagnosis was confirmed by immunohistochemical studies that showed that the neoplastic cells were positive for CD15 and CD30 and negative for CD45 (LCA). In situ hybridization for Epstein-Barr virus smallencoded RNA was also positive in the neoplastic cells. Hodgkin lymphoma arising in the rectum of immunocompetent patients is rare, with only 12 cases (including this one) reported in the literature . Of these, the diagnosis was confirmed by immunohistochemical studies in only two cases, and this is the first case assessed and shown to be positive for Epstein-Barr virus. D 2005 Elsevier Inc. All rights reserved.
Index words:
Classical Hodgkin lymphoma; Rectum; Epstein Barr virus
1. Introduction Hodgkin Lymphoma (HL) primarily arising in the gastrointestinal tract has been reported in 1% to 3% of all patients with HL [1-3]. However, this frequency is likely to be an overestimation, as many previously reported cases most likely were examples of secondary involvement of the gastrointestinal tract in patients with nodal disease [4]. The stomach and small intestine are reported to be the most common gastrointestinal sites involved by HL, and many affected patients have associated inflammatory bowel disease or immunodeficiency states [5-7]. Epstein-Barr (EBV) virus is a unbiquitous herpes virus that is the causative agent of infectious mononucleosis and is consistently associated with endemic (African) cases of Burkitt lymphoma and nasopharyngeal carcinoma [8]. Epstein-Barr virus is also present in a significant proportion of cases of HL. In the United States and Europe, EBV is
B Dr Gualco performed this work while a visiting pathologist and as a recipient of a fellowship granted by the Fulbright Commission. T Corresponding author. Department of Hematopathology, Box 72, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030. Tel.: +1 713 794 5446; fax: +1 713 745 0736. E-mail address: [email protected] (L.J. Medeiros).
1092-9134/$ – see front matter D 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.anndiagpath.2004.08.011
present in the 60% to 70% of cases of mixed cellularity type and 20% to 40% of cases of nodular sclerosis type [9,10]. By contrast, in less industrialized nations such as Mexico, EBV is much more common in HL, regardless of histologic type [11-13]. There is also a high frequency of EBV in HL arising in Hispanic patients in the United States, regardless of patient age and immune status [14]. Thus, both environmental and genetic factors may explain the high frequency of EBV in Mexican patients. We present an unusual case of classical HL, nodular sclerosis type, arising in the rectum of an immunocompetent 81-year-old Mexican man. 2. Case report An 81-year-old Mexican man presented to his physician, 10 months after onset of symptoms, with mucous bloody diarrhea, irritability, and weight loss (15 kg). Digital rectal examination revealed a friable tumor located in the rectum. The remainder of the physical examination was unremarkable. No superficial lymphadenopathy or hepatomegaly was indentified. Pertinent clinical history included typhoid fever 18 years earlier, which resolved without complications. Computed tomography scan of the abdomen and pelvis showed an ill-defined tumor, 8.0 7.0 cm in greatest
J.R. Valbuena et al. / Annals of Diagnostic Pathology 9 (2005) 38 – 42
dimensions, located in the rectum with extension through the rectal wall into peri-rectal fat. Mild regional lymphadenopathy was also identified. No periaortic lymphadenopathy or lesions in the liver or spleen were detected. The lungs were unremarkable. A complete blood count was normal and serum carcinoembryogenic antigen level was within normal range, 0.6 ng/dL (reference range, 0 to 6 ng/dL). Bone marrow aspiration and biopsy showed cellular bone marrow with no evidence of neoplasm. The clinical diagnosis of localized rectal carcinoma was established, and the patients underwent abdominal-perineal rectal resection. 3. Materials and methods Formalin-fixed, paraffin-embedded tissue blocks and hematoxylin-eosin stained slides of the rectal mass and pertinent clinical and pathology reports were received in
39
consultation from the Hospital Civil de Guadalajara in Guadalajara, Mexico. 3.1. Immunohistochemistry and in situ hybridization Immunohistochemistry stains were performed using formalin-fixed, paraffin-embedded tissue sections, heatinduced epitope retrieval, an avidin-biotin complex method, and an automated immunostainer (Ventana Medical System, Tucson, AZ). The antibodies used were specific for CD15 (Becton-Dickinson, San Jose, CA), CD3, CD20, CD30 and CD45 (DAKO, Carpinteria, CA), as previously described [15]. In situ hybridization analysis for EBV small-encoded RNA (EBER) was performed using formalin-fixed paraffinembedded sections, a fluorescein-labeled peptide nucleic acid probe specific for EBER, and the DAKO hybridization kit according to the manufacturer’s instructions.
Fig. 1. (A) Prominent tumor nodules separated by dense fibrous bands. (Hematoxylin-eosin stain; magnification 200.) (B) Lacunar cell, in a polymorphous background composed of reactive lymphocytes, plasma cells, histiocytes, and scattered eosinophils. (Hematoxylin-eosin stain; magnification 500.) (C) Large neoplastic cells show granular cytoplasmic positivity for CD15 (Magnification 500.) (Inset) Neoplastic cells show membranous and golgi pattern of staining for CD30. (Magnification 500.) (D) In situ hybridization demonstrates Epstein-Barr virus RNA in the large neoplastic cells. (Magnification 1,000.)
40
J.R. Valbuena et al. / Annals of Diagnostic Pathology 9 (2005) 38 – 42
4. Results 4.1. Gross findings, histology, and immunohistochemistry The specimen was a segment of rectum within which an 8 cm, irregular tan-gray ulcerated mass was present. Cross sections of the mass showed that the tumor invaded through the rectal wall and extended into the peri-rectal adipose tissue. Histologic sections of the rectal mass revealed large tumor nodules separated by broad fibrous bands (Fig. 1A). Within these nodules, large neoplastic cells consistent with lacunar cells (Fig. 1B) were identified in a polymorphous inflammatory infiltrate composed a mixture of granulocytes, plasma cells, histiocytes, small lymphocytes, and scattered eosinophils. Some areas of the tumor showed extensive coagulative necrosis. Immunohistochemical studies showed that the neoplastic cells were positive for CD15 and CD30 with a paranuclear and membranous pattern of staining (Fig. 1C). The neoplastic cells were negative for CD3, CD20, and CD45 (LCA). The antibodies specific for CD3 and CD20 highlighted reactive T and B cells. In situ hybridization for EBER was positive in virtually all the neoplastic cells (Fig. 1D). The histologic, immunohistochemical, and in situ hybridization findings supported the diagnosis of classical HL, nodular sclerosis type. Peri-rectal lymph nodes were also examined histologically and showed only reactive changes. There was no evidence of HL in the lymph nodes. 5. Discussion Primary colorectal lymphomas are rare, and most cases are non-Hodgkin lymphomas (NHL) [3]. In an extensive review of the literature, Thomas et al [3] identified 940 cases of
lymphoma involving the gastrointestinal tract, with 242 involving the colon and rectum. In this subgroup, 147 neoplasms (61%) were classified as NHL and 95 (39%) as HL [3]. A major problem that the authors contented with is that many cases reported in the past lack complete staging information. Nevertheless, the authors concluded that most of these 242 neoplasms did not arise in the gastrointestinal tract, and that the frequency of primary rectal lymphoma is very low. Thomas et al [3] did not mention the status of the patient’s immune system, or if there was a history of inflammatory bowel disease, most likely because this information was not available in most case series and case reports. It is known that lymphomas of the gastrointestinal tract are more common in patients with immunodeficiency (eg, human immunodeficiency virus infection) [16 -20], or in patients with both major types of inflammatory bowel disease [5-7]. In their review, Thomas et al [3] concluded that 26 cases of HL most likely arose in the colon (full length), of which six cases involved the rectum. In our review of the literature, we have identified a total of 12 cases of HL arising in the rectum in presumably immunocompetent patients (including the current case and those in the report by Thomas et al). All 12 patients are summarized in Table 1 [21-34]. For the seven immunocompetent patients with demographic data, age ranged from 40 to 81 years and there was a marked male predominance (six men, one woman). Including the case reported herein, only two cases in immunocompetent patients were confirmed using immunohistochemical methods and this case is the only one assessed for EBV. In our review of the literature, we also identified five cases of HL involving the rectum in HIV-infected patients, also summarized in Table 1 [29-31,33,34]. Although the rectum is an uncommon site involvement by HL immunocompetent patients, involvement of this anatomic site by
Table 1 Summary of Cases of Rectal Hodgkin Lymphoma Reported in the Literature Source
No.
Age/Sex
Immunodeficiency
Site
Histologic Type
IHC
EBV
Stage
Warren and Lulenski [21] Portman et al [22] Allen and Donalson [23] Warren and Littlefield [24] Dawson et al [25] Shapiro [26] Kuhlmann [27] Tabuse et al [28] Pagano et al [32] Valbuena (this case) Coonley et al [29] Picard et al [30] Marquez–Moreno et al [31] Sapp et al [33] Simpson et al [34]
1 2 1 1 1 1 1 2 1 1 1 1 1 1 1
NA/NA NA/NA NA/NA NA/NA 53/F 46/M 45/M 40/M 67/M 81/M 33/M 51/M 33/M 33/M 39/M
NA NA NA NA NA NA NA NA – – HIV HIV HIV HIV HIV
rectum rectum rectum rectum rectum rectosigmoid rectosigmoid rectum rectum rectum rectum rectum ano–rectal ano–rectal rectum
NOS NOS NOS NOS NOS NOS NOS NOS NOS NS NOS MC NOS MC NOS
NA NA NA NA NA NA NA NA +/+ +/+ NA NA NA +/+ +/+
NA NA NA NA NA NA NA NA NA + NA +z NA + NA
IE IE IE IE IE IIE IE IE IE IE IIBEy IE IIBEy IIEy IVB§
IHC, Immunohistochemistry; MC, mixed cellularity; NS, nodular sclerosis; HIV, human immunodeficiency virus; EBV, Epstein–Barr virus; NA, not available; NOS, not otherwise specified. y Regional lymphadenopathy. z Detected by serologic studies only. § Focal bone marrow involvement.
J.R. Valbuena et al. / Annals of Diagnostic Pathology 9 (2005) 38 – 42
HL may be more common in HIV-infected patients [20]. Two of these five cases reported were assessed for EBV and both were positive . It is known that an increase in the prevalence EBV infection in classical HL is seen in patients with coexisting HIV infection [20]. The lack of complete clinical and immunohistochemical data for most of the cases listed in Table 1 also calls into question the diagnosis of primary rectal HL. It is possible that some of these cases may be examples of secondary involvement of the rectum nodal HL. It is also possible that some of these cases may have been examples of NHL. Cases of NHL, particularly large B-cell lymphoma and peripheral T-cell lymphoma, can have large pleomorphic cells or ReedSternberg-like cells and be misclassified as HL without immunohistochemical confirmation [2,35]. Thus, it is likely that HL arising in the rectum is even more rare than suggested by our literature review. Symptoms of HL involving in the large bowel include crampy abdominal pain, anorexia, weight loss, melena, change in bowel habits, obstruction, and bleeding [3]. These symptoms are not specific and can be present in other types of gastrointestinal disorders, especially inflammatory bowel disease [5-7]. However, some patients may have obstructive symptoms because of the presence of polypoid masses or annular constricting lesions. This presentation may be more common in the rectum because a number of case reports of rectal HL described the tumors as polypoid, ulcerative, multinodular, and annular constricting lesions [21-34]. It is well known that the frequency of EBV in HL correlates with country of origin, with a lower frequency in industrialized countries and a higher frequency in developing countries [9-13]. Epstein-Barr virus has been shown to be common in HL cases from Mexico, in up to 67% of cases [11-13]. A number of socioeconomic factors are thought to be involved in the frequency of EBV in HL in patients from developing countries, such as poor living conditions, number of siblings, and inadequate nutrition, perhaps increasing the risk of exposure to EBV early in life. In the present case, the patient was native from a rural area in Mexico, but we have no other information related to the patient’s siblings or living conditions. In summary, we report an unusual case of HL arising in the rectum of 81-year-old immunocompetent man. Primary HL of the rectum in immunocompetent patients is uncommon, and including this case, 12 cases of HL arising in the rectum are reported in the literature. References [1] Aozasa K, Tsujimoto M, Inoue A, et al. Primary gastrointestinal lymphoma A clinicopathologic study of 102 patients. Oncology 1985; 42:97 - 103. [2] Devaney K, Jaffe ES. The surgical pathology of gastrointestinal Hodgkin’s disease. Am J Clin Pathol 1991;95:794 - 801. [3] Thomas DB, Huston BM, Lamm KR, et al. Primary Hodgkin’s disease of the sigmoid colon. A case report and review of the literature. Arch Pathol Lab Med 1997;121:528 - 32.
41
[4] Perez MT, Cabella-Inchausti B, Castellano-Sanchez A, et al. Primary gastroesophageal-ileal Hodgkin lymphoma. A case report and review of the literature. Arch Pathol Lab Med 2002;126:1534 - 7. [5] Kelly MD, Stuart M, Tschuchnigg M, et al. Primary intestinal Hodgkin’s disease complicating ileal Crohn’s disease. Aus N Z J Surg 1997;67:485 - 9. [6] Morrison PD, Whittaker M. A case of Hodgkin’s disease complicating Chron’s disease. Clin Oncol 1982;8:271 - 2. [7] Kumar S, Fend F, Quintanilla-Martinez L, et al. Epstein-Barr virus positive primary gastrointestinal Hodgkin’s disease: Association with inflammatory bowel disease and immunosuppression. Am J Surg Pathol 2000;24:66 - 73. [8] Young LS, Murray PG. Epstein-Barr virus and oncogenesis: From latent genes to tumours. Oncogene 2003;22:5108 - 21. [9] Herling M, Rassidakis GZ, Medeiros LJ, et al. Expression of Epstein-Barr virus latent membrane protein-1 in Hodgkin and ReedSternberg cells of classical Hodgkin lymphoma: Association with presenting features, serum interleukin 10 levels, and clinical outcome. Clin Cancer Res 2003;9:2114 - 20. [10] Jarrett RF, Krajewski AS, Angus B, et al. The Scotland and Newcastle epidemiological study of Hodgkin’s disease: Impact of histopathological review and EBV status and incidence estimates. J Clin Pathol 2003;56:811 - 6. [11] Dirnhofer S, Angeles-Angeles A, Ortiz-Hidalgo C, et al. High prevalence of a 30-pair deletion in the Epstein-Barr Virus latent membrane protein 1 gene and of strain type B EBV in Mexican classical Hodgkin’s disease and reactive lymphoid tissue. Hum Pathol 1999;39:781 - 7. [12] Quintanilla-Martinez L, Gamboa A, Gamez I, et al. Association of Epstein Barr virus latent membrane protein and Hodgkin’s disease in Mexico. Mod Pathol 1995;8:675 - 9. [13] Zarate-Osorno A, Roman LN, Kingma DW, et al. Hodgkin’s disease in Mexico. Prevalence of Epstein-Barr virus sequences and correlations with histologic subtype. Cancer 1995;15:1360 - 6. [14] Gulley ML, Eagan PA, Quintanilla-Martinez L, et al. Epstein-Barr virus DNA is abundant and monoclonal in the Reed-Sternberg cells of Hodgkin’s disease: Association with mixed cellularity subtype and Hispanic American ethnicity. Blood 1994;83:1595 - 602. [15] Park CK, Manning JT, Battifora H, et al. Follicle center lymphoma and Warthin tumor involving the same anatomic site. Report of two cases and review of the literature. Am J Clin Pathol 2000;113:113 - 9. [16] Burkes RL, Meyer PR, Gill PS, et al. Rectal lymphoma in homosexual men. Arch Int Med 1986;146:913 - 5. [17] Gelb AB, Medeiros LJ, Chen YY, et al. Hodgkin’s disease of the esophagus. Am J Clin Pathol 1997;108:593 - 8. [18] Imrie KR, Sawka CA, Kutas G, et al. HIV-associated lymphoma of the gastrointestinal tract: The University of Toronto AIDS-lymphoma study group experience. Leuk Lymphoma 1995;16:343 - 9. [19] Young G. Lymphoma at uncommon sites. Hematol Oncol 1999;17:53 - 83. [20] Ioachim HL, Antonescu C, Giancotti F, et al. EBV-associated anorectal lymphomas in patients with acquired immune deficiency syndrome. Am J Surg Pathol 1997;21:997 - 1006. [21] Warren S, Lulenski CR. Primary solitary lymphoid tumors of the gastro-intestinal tract. Ann Surg 1942;115:1 - 12. [22] Portmann UV, Dunne EF, Hazard JB. Manifestations of Hodgkin’s disease of the gastrointestinal tract. Am J Roentgenol Radium Ther Nucl Med 1954;72:772 - 87. [23] Allen AW, Donaldson G, Sniffen RC, et al. Primary malignant lymphoma of the gastrointestinal tract. Ann Surg 1954;140: 428 - 37. [24] Warren KW, Littlefield JB. Malignant lymphomas of the gastrointestinal tract. Surg Clin North Am 1955;35:735 - 46. [25] 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 1961;48:80 - 9.
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[26] Shapiro HA. Primary Hodgkin’s disease of the rectum. Arch Intern Med 1961;107:270 - 3. [27] Kuhlmann HW. Lymphogranulomatosis of the recto-sigmoid region: A rare primary manifestation and localization. Dtsch Med Wochenschr 1975;100:553 - 4. [28] Tabuse K, Katsumi M, Yamaue H, et al. A case of Hodgkin’s disease of the rectum. Nippon Geka Hokan 1983;52:710 - 7. [29] Coonley CJ, Straus DJ, Flippa D, et al. Hodgkin’s disease presenting with rectal symptoms in homosexual male. A case report and review of the literature. Cancer Inv 1984;2:279 - 84. [30] Picard O, De Gramont A, Krulik M, et al. Rectal Hodgkin disease and the acquired immunodeficiency syndrome. Ann Intern Med 1987; 106:775.
[31] Marquez-Moreno AJ, Rubio-Garrido J, Rueda-Dominguez A, et al. Anorectal Hodgkin disease in an HIV-infected patient. Med Clin 1999; 112:598 - 9. [32] Pagano L, Ratto C, Teofili L, et al. Isolated primary Hodgkin’s disease of rectum. Hematologica 2000;85:986 - 7. [33] Sapp M, Perez-Ordonez B, Brenneman F, et al. EBV-associated perianal Hodgkin’s disease in an HIV-positive individual. Am J Hematol 2001;66:42 - 5. [34] Simpson L, Taylor S, Piotrowski A. Case 3. Hodgkin’s disease: Rectal presentation. J Clin Oncol 2004;22:196 - 8. [35] Vadmal MS, LaValle GP, DeYoung BR, et al. Primary localized extranodal Hodgkin disease of the transverse colon. Arch Pathol Lab Med 2000;124:1824 - 7.
Case report
Classical hodgkin lymphoma arising in the rectumB Jose R. Valbuena, MDa, Gabriela Gualco, MDa, Ismael Espejo-Plascencia, MDa, L. Jeffrey Medeiros, MDb,T a
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX b Department of Pathology, Hospital Civil de Guadalajara, Guadalajara, Mexico
Abstract
We report a case of an 81-year-old immunocompetent Mexican man who underwent an abdominalperineal rectal resection for a mass clinically thought to be carcinoma. Histopathologic diagnosis revealed classical Hodgkin lymphoma, nodular sclerosis type, involving the rectum. The diagnosis was confirmed by immunohistochemical studies that showed that the neoplastic cells were positive for CD15 and CD30 and negative for CD45 (LCA). In situ hybridization for Epstein-Barr virus smallencoded RNA was also positive in the neoplastic cells. Hodgkin lymphoma arising in the rectum of immunocompetent patients is rare, with only 12 cases (including this one) reported in the literature . Of these, the diagnosis was confirmed by immunohistochemical studies in only two cases, and this is the first case assessed and shown to be positive for Epstein-Barr virus. D 2005 Elsevier Inc. All rights reserved.
Index words:
Classical Hodgkin lymphoma; Rectum; Epstein Barr virus
1. Introduction Hodgkin Lymphoma (HL) primarily arising in the gastrointestinal tract has been reported in 1% to 3% of all patients with HL [1-3]. However, this frequency is likely to be an overestimation, as many previously reported cases most likely were examples of secondary involvement of the gastrointestinal tract in patients with nodal disease [4]. The stomach and small intestine are reported to be the most common gastrointestinal sites involved by HL, and many affected patients have associated inflammatory bowel disease or immunodeficiency states [5-7]. Epstein-Barr (EBV) virus is a unbiquitous herpes virus that is the causative agent of infectious mononucleosis and is consistently associated with endemic (African) cases of Burkitt lymphoma and nasopharyngeal carcinoma [8]. Epstein-Barr virus is also present in a significant proportion of cases of HL. In the United States and Europe, EBV is
B Dr Gualco performed this work while a visiting pathologist and as a recipient of a fellowship granted by the Fulbright Commission. T Corresponding author. Department of Hematopathology, Box 72, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030. Tel.: +1 713 794 5446; fax: +1 713 745 0736. E-mail address: [email protected] (L.J. Medeiros).
1092-9134/$ – see front matter D 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.anndiagpath.2004.08.011
present in the 60% to 70% of cases of mixed cellularity type and 20% to 40% of cases of nodular sclerosis type [9,10]. By contrast, in less industrialized nations such as Mexico, EBV is much more common in HL, regardless of histologic type [11-13]. There is also a high frequency of EBV in HL arising in Hispanic patients in the United States, regardless of patient age and immune status [14]. Thus, both environmental and genetic factors may explain the high frequency of EBV in Mexican patients. We present an unusual case of classical HL, nodular sclerosis type, arising in the rectum of an immunocompetent 81-year-old Mexican man. 2. Case report An 81-year-old Mexican man presented to his physician, 10 months after onset of symptoms, with mucous bloody diarrhea, irritability, and weight loss (15 kg). Digital rectal examination revealed a friable tumor located in the rectum. The remainder of the physical examination was unremarkable. No superficial lymphadenopathy or hepatomegaly was indentified. Pertinent clinical history included typhoid fever 18 years earlier, which resolved without complications. Computed tomography scan of the abdomen and pelvis showed an ill-defined tumor, 8.0 7.0 cm in greatest
J.R. Valbuena et al. / Annals of Diagnostic Pathology 9 (2005) 38 – 42
dimensions, located in the rectum with extension through the rectal wall into peri-rectal fat. Mild regional lymphadenopathy was also identified. No periaortic lymphadenopathy or lesions in the liver or spleen were detected. The lungs were unremarkable. A complete blood count was normal and serum carcinoembryogenic antigen level was within normal range, 0.6 ng/dL (reference range, 0 to 6 ng/dL). Bone marrow aspiration and biopsy showed cellular bone marrow with no evidence of neoplasm. The clinical diagnosis of localized rectal carcinoma was established, and the patients underwent abdominal-perineal rectal resection. 3. Materials and methods Formalin-fixed, paraffin-embedded tissue blocks and hematoxylin-eosin stained slides of the rectal mass and pertinent clinical and pathology reports were received in
39
consultation from the Hospital Civil de Guadalajara in Guadalajara, Mexico. 3.1. Immunohistochemistry and in situ hybridization Immunohistochemistry stains were performed using formalin-fixed, paraffin-embedded tissue sections, heatinduced epitope retrieval, an avidin-biotin complex method, and an automated immunostainer (Ventana Medical System, Tucson, AZ). The antibodies used were specific for CD15 (Becton-Dickinson, San Jose, CA), CD3, CD20, CD30 and CD45 (DAKO, Carpinteria, CA), as previously described [15]. In situ hybridization analysis for EBV small-encoded RNA (EBER) was performed using formalin-fixed paraffinembedded sections, a fluorescein-labeled peptide nucleic acid probe specific for EBER, and the DAKO hybridization kit according to the manufacturer’s instructions.
Fig. 1. (A) Prominent tumor nodules separated by dense fibrous bands. (Hematoxylin-eosin stain; magnification 200.) (B) Lacunar cell, in a polymorphous background composed of reactive lymphocytes, plasma cells, histiocytes, and scattered eosinophils. (Hematoxylin-eosin stain; magnification 500.) (C) Large neoplastic cells show granular cytoplasmic positivity for CD15 (Magnification 500.) (Inset) Neoplastic cells show membranous and golgi pattern of staining for CD30. (Magnification 500.) (D) In situ hybridization demonstrates Epstein-Barr virus RNA in the large neoplastic cells. (Magnification 1,000.)
40
J.R. Valbuena et al. / Annals of Diagnostic Pathology 9 (2005) 38 – 42
4. Results 4.1. Gross findings, histology, and immunohistochemistry The specimen was a segment of rectum within which an 8 cm, irregular tan-gray ulcerated mass was present. Cross sections of the mass showed that the tumor invaded through the rectal wall and extended into the peri-rectal adipose tissue. Histologic sections of the rectal mass revealed large tumor nodules separated by broad fibrous bands (Fig. 1A). Within these nodules, large neoplastic cells consistent with lacunar cells (Fig. 1B) were identified in a polymorphous inflammatory infiltrate composed a mixture of granulocytes, plasma cells, histiocytes, small lymphocytes, and scattered eosinophils. Some areas of the tumor showed extensive coagulative necrosis. Immunohistochemical studies showed that the neoplastic cells were positive for CD15 and CD30 with a paranuclear and membranous pattern of staining (Fig. 1C). The neoplastic cells were negative for CD3, CD20, and CD45 (LCA). The antibodies specific for CD3 and CD20 highlighted reactive T and B cells. In situ hybridization for EBER was positive in virtually all the neoplastic cells (Fig. 1D). The histologic, immunohistochemical, and in situ hybridization findings supported the diagnosis of classical HL, nodular sclerosis type. Peri-rectal lymph nodes were also examined histologically and showed only reactive changes. There was no evidence of HL in the lymph nodes. 5. Discussion Primary colorectal lymphomas are rare, and most cases are non-Hodgkin lymphomas (NHL) [3]. In an extensive review of the literature, Thomas et al [3] identified 940 cases of
lymphoma involving the gastrointestinal tract, with 242 involving the colon and rectum. In this subgroup, 147 neoplasms (61%) were classified as NHL and 95 (39%) as HL [3]. A major problem that the authors contented with is that many cases reported in the past lack complete staging information. Nevertheless, the authors concluded that most of these 242 neoplasms did not arise in the gastrointestinal tract, and that the frequency of primary rectal lymphoma is very low. Thomas et al [3] did not mention the status of the patient’s immune system, or if there was a history of inflammatory bowel disease, most likely because this information was not available in most case series and case reports. It is known that lymphomas of the gastrointestinal tract are more common in patients with immunodeficiency (eg, human immunodeficiency virus infection) [16 -20], or in patients with both major types of inflammatory bowel disease [5-7]. In their review, Thomas et al [3] concluded that 26 cases of HL most likely arose in the colon (full length), of which six cases involved the rectum. In our review of the literature, we have identified a total of 12 cases of HL arising in the rectum in presumably immunocompetent patients (including the current case and those in the report by Thomas et al). All 12 patients are summarized in Table 1 [21-34]. For the seven immunocompetent patients with demographic data, age ranged from 40 to 81 years and there was a marked male predominance (six men, one woman). Including the case reported herein, only two cases in immunocompetent patients were confirmed using immunohistochemical methods and this case is the only one assessed for EBV. In our review of the literature, we also identified five cases of HL involving the rectum in HIV-infected patients, also summarized in Table 1 [29-31,33,34]. Although the rectum is an uncommon site involvement by HL immunocompetent patients, involvement of this anatomic site by
Table 1 Summary of Cases of Rectal Hodgkin Lymphoma Reported in the Literature Source
No.
Age/Sex
Immunodeficiency
Site
Histologic Type
IHC
EBV
Stage
Warren and Lulenski [21] Portman et al [22] Allen and Donalson [23] Warren and Littlefield [24] Dawson et al [25] Shapiro [26] Kuhlmann [27] Tabuse et al [28] Pagano et al [32] Valbuena (this case) Coonley et al [29] Picard et al [30] Marquez–Moreno et al [31] Sapp et al [33] Simpson et al [34]
1 2 1 1 1 1 1 2 1 1 1 1 1 1 1
NA/NA NA/NA NA/NA NA/NA 53/F 46/M 45/M 40/M 67/M 81/M 33/M 51/M 33/M 33/M 39/M
NA NA NA NA NA NA NA NA – – HIV HIV HIV HIV HIV
rectum rectum rectum rectum rectum rectosigmoid rectosigmoid rectum rectum rectum rectum rectum ano–rectal ano–rectal rectum
NOS NOS NOS NOS NOS NOS NOS NOS NOS NS NOS MC NOS MC NOS
NA NA NA NA NA NA NA NA +/+ +/+ NA NA NA +/+ +/+
NA NA NA NA NA NA NA NA NA + NA +z NA + NA
IE IE IE IE IE IIE IE IE IE IE IIBEy IE IIBEy IIEy IVB§
IHC, Immunohistochemistry; MC, mixed cellularity; NS, nodular sclerosis; HIV, human immunodeficiency virus; EBV, Epstein–Barr virus; NA, not available; NOS, not otherwise specified. y Regional lymphadenopathy. z Detected by serologic studies only. § Focal bone marrow involvement.
J.R. Valbuena et al. / Annals of Diagnostic Pathology 9 (2005) 38 – 42
HL may be more common in HIV-infected patients [20]. Two of these five cases reported were assessed for EBV and both were positive . It is known that an increase in the prevalence EBV infection in classical HL is seen in patients with coexisting HIV infection [20]. The lack of complete clinical and immunohistochemical data for most of the cases listed in Table 1 also calls into question the diagnosis of primary rectal HL. It is possible that some of these cases may be examples of secondary involvement of the rectum nodal HL. It is also possible that some of these cases may have been examples of NHL. Cases of NHL, particularly large B-cell lymphoma and peripheral T-cell lymphoma, can have large pleomorphic cells or ReedSternberg-like cells and be misclassified as HL without immunohistochemical confirmation [2,35]. Thus, it is likely that HL arising in the rectum is even more rare than suggested by our literature review. Symptoms of HL involving in the large bowel include crampy abdominal pain, anorexia, weight loss, melena, change in bowel habits, obstruction, and bleeding [3]. These symptoms are not specific and can be present in other types of gastrointestinal disorders, especially inflammatory bowel disease [5-7]. However, some patients may have obstructive symptoms because of the presence of polypoid masses or annular constricting lesions. This presentation may be more common in the rectum because a number of case reports of rectal HL described the tumors as polypoid, ulcerative, multinodular, and annular constricting lesions [21-34]. It is well known that the frequency of EBV in HL correlates with country of origin, with a lower frequency in industrialized countries and a higher frequency in developing countries [9-13]. Epstein-Barr virus has been shown to be common in HL cases from Mexico, in up to 67% of cases [11-13]. A number of socioeconomic factors are thought to be involved in the frequency of EBV in HL in patients from developing countries, such as poor living conditions, number of siblings, and inadequate nutrition, perhaps increasing the risk of exposure to EBV early in life. In the present case, the patient was native from a rural area in Mexico, but we have no other information related to the patient’s siblings or living conditions. In summary, we report an unusual case of HL arising in the rectum of 81-year-old immunocompetent man. Primary HL of the rectum in immunocompetent patients is uncommon, and including this case, 12 cases of HL arising in the rectum are reported in the literature. References [1] Aozasa K, Tsujimoto M, Inoue A, et al. Primary gastrointestinal lymphoma A clinicopathologic study of 102 patients. Oncology 1985; 42:97 - 103. [2] Devaney K, Jaffe ES. The surgical pathology of gastrointestinal Hodgkin’s disease. Am J Clin Pathol 1991;95:794 - 801. [3] Thomas DB, Huston BM, Lamm KR, et al. Primary Hodgkin’s disease of the sigmoid colon. A case report and review of the literature. Arch Pathol Lab Med 1997;121:528 - 32.
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