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HIV-associated oral pleomorphic B-cell malignant lymphoma
VoL 84 No. 2 August 1997
ORAL MEDICINE
Editors: Jed Jacobson and Margot Van Dis
HIV-Associated oral pleomorphic B-cell malignant lymphoma Teresa V~izquez-Pifieiro, PhD, MD, a Lourdes Viana de Frfas, MD, b Eva Crist6bal, PhD, c Jaime Cosfn, PhD, MD, d and Javier MenArguez, MD, PhD, e Madrid, Spain HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAIq0N
A 48-year-old HIV-seropositive homosexual patient presented with an ulcerative lesion in the left side of the soft palate, extensively involving local soft tissue structures. On histologic evaluation the lesion appeared to be a large-cell high-grade B-cell pleomorphic lymphoma with anaplastic and plasmacytoid features harboring Epstein-Barr virus genome in the tumor cells. Although known to be associated With HIV infection, this is a rare subtype of a malignant lymphoma arising in a patient positive for HIV. lfs meaning is yet unknown in biologic and prognostic terms. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod
1997;84:142-5)
Non-Hodgkin's lymphoma (NHL) is the second most c o m m o n malignancy associated with HIV infection. Its incidence is rapidly increasing, 1-3 with reports of occurrence in from 3% to 10% of patients with AIDS. 4-6 HIV-associated N H L s d e v e l o p most frequently in intravenous drug abusers. 3, 7, 8 Although approximately 70% of these are B-cell lesions, 20% are derived from T cells. In most cases, they are high-grade (HG) tumors and belong to a reduced number of histologic subtypes.5, 6 In approximately 5% of the cases, the presenting lesion is in the oral cavity, often resembling a less morbid process, z, 9-24 We report an unusual type of B-cell HG N H L arising in the oral cavity and discuss its clinical and histologic features.
CASE REPORT A 48-year-old homosexual man was admitted to the Department of Infectious Diseases of the Gregorio Marafi6n Hospital in May 1994 because of odyn0phagia occurring in the past 5 months. He also reported left pharyngeal pain radiating to the face and ear and homolateral nasal obstruction. HIV seropositivity had been discovered in 1987. Since then relapsing genital herpes and oral aphthae, gonococcal nreaDepartment of Oral Medicine. bDepartment of Oral Medicine. CDepartment of Pathology. aDepartment of Clinical Microbiology. eDepartment of Pathology. Partially supported by a grant from the Fondo de Investigaciones Sanitarias FIS 93/0016-05. Received for publication July 24, 1996; revised Sept. 27, 1996; accepted Feb. 6, 1997. Copyright © 1997 by Mosby-Year Book, Inc. 1079-2104/97/$5.00 + 0 7/13/81171
142
thritis, oral candidiasis, and cytomegalovirus retinitis had been diagnosed. He had been under treatment with AZT (500 mg/day) since 1989 and with dideoxiinosina (400 rag/day) since 1993. He was considered to be at C3 stage according to the Revised Centers for Disease Control HIV Classification System. 25 Peripheral CD4+ blood counts were less than 25 cells/mm3. Oral examination disclosed a deep nonbleeding 3 cm ulcer in the left soft palate. The ulcer showed coarse margins and necrotic areas and was covered by a yellowish fibrinous exudate. The lesion partially destroyed the left soft palate and pharyngeal pillars, sparing the uvulae and posterior soft palatine edge (Fig. 1). Radiographs did not disclose dental or osseous involvement. A craniofacial computed tomography scan confirmed the presence of an extensive lesion involving the oropharynx and infiltrating the contralateral structures through the palate including the parapharyngeal space, internal pterygoid muscle, and local adipose tissues. The nasal fossae were occupied by polypoid lesions. The left maxillary sinus was obliterated, and erosion of the superior and posterior wall could be observed (Fig. 2). After two incisional biopsies were performed, a diagnosis of diffuse HG anaplastic large-cell B-cell lymphoma (ALCL) with plasmacytoid differentiation was established. Angiocentric areas and a striking zonal pattern were seen. Although plasmacytoid differentiation was easily observed in areas, in others the tumor showed predominantly anaplastic cytologic characteristics, lmmunohistochemical techniques disclosed CD20 positivity and cytoplasmic l¢-immunoglobulin light chain restriction in the areas with plasmacytic differentiation. The predominantly anaplastic areas were positive for CD30 (Ki-1) and negative for the other two markers (Fig. 3). The presence of Epstein-Barr virus (EBV) genome could be demonstrated in the biopsy specimens with the aid of
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY Volume 84, Number 2
Vdsquez-Piheiro et al. 143
Fig. 1. Uvulae and posterior soft palatine edge are intact.
Fig. 2. Craniofacial computed tomography scan. A, Coronal computed tomography disclosed soft tissue mass occupying left nasal fossae and left maxillary sinus. B, Axial computed tomography reveals tumoral mass in palatine tonsil occupying oropharyngeal space.
polymerase chain reaction and three different sets of primers targeting different regions of the EBV genome.26 This finding was confirmed by in situ hybridization for Epstein-Ban" encoded RNA. 26 By this last technique we were able to specifically pinpoint the signal within the neoplastic ele-
ments. Attempts to isolate any microorganisms from biopsy were unsuccessful. After the staging of the tumor was completed, no additional neoplastic locations could be demonstrated. In May 1994 a first round of polychemotherapy (cyclophosphamide, adri-
144 Vdzquez-Piffeiro et al.
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY August 1997
Fig. 3. In situ hybridization for Epstein-Barr encoded RNA. Lymphomatous infiltrates involving minor salivary glands. Although positiv e signals (dark brown nuclei, big arrowhead) are frequently present in neoplastic cells, epithelial cells are constantly negative (small arrowhead). (Hematoxylin-eosin counterstaining; original magnification x40.)
amycin, vincristine, and prednisone) was started. The patient had neutropenia and septicemia with Staphylococcus aureus shortly after the second cycle was started; the patient died.
DISCUSSION It has been repeatedly shown that HIV infection and the subsequent immunosuppression results in an increased risk of malignant d i s e a s e s Although 40% of patients with AIDS have a malignant tumor at the time of the initial diagnosis, in one series the percentage increased up to 70% over the course of the disease. 4 Head and neck NHLs originate mainly in cervical lymph nodes and Waldeyer's Ring structures, including palatine tonsils and nasopharynx, z4,zs Primary oral NHLs were rare before the AIDS era, constituting only 4% to 5% of extranodal NHLs. 11-15,28 Of these tumors, approximately 20% to 32% originated in the palate, ~2,13 and only 35% of the cases showed osseous involvement.~ 1,12These tumors were almost exclusively B-cell lesions corresponding to centroblastic, diffuse histiocytic, and immunoblastic histologic subtypes) 4A5 Taken as a whole, AIDS-associated NHLs tend to be aggressive, extranodal, HG tumors frequently involving the central nervous system, bone marrow, and the gastrointestinal tract. 8,16,17 The vast majority of them (97%) are HG B-cell tumors and can be classified as Burkitt-like, immunoblastic, and centroblastic subtypes. 2°,29 HG tumors follow a very aggressive course
with a poor prognosis and a high mortality rate. Currently, the median survival of patients with AIDS-related lymphomas following treatment is 5 to 11 months. 9-11,3°32 Intraoral HIV-associated lymphomas have been reported to arise in the palate, retromolar area, gingiva, tongue, tonsils, mandible, maxillary sinus, and alveolar ridges. 19 In this patient, the tumor was located in the palatine tonsil with involvement of the maxillary sinus, nasal fossae, and oropharynx, without extension into adjacent bone. ALCLs are infrequently associated with HIV infection. 33 Although known to arise in extranodal locations, only recently HIV-related ALCL has been described to originate in the oral cavity. 16 Compared with other ALCLs, this case showed a striking morphologic and immunohistochemical variability in immunoglobulin light chain and CD30 antigen expression. These features are unusual in conventional anaplastic large-cell lymphomas. We have not been able to find previous reports of other related tumors disclosing these features in the oral cavity. In our experience this peculiar morphology and immunohistochemistry appears to be a common finding in several AIDS-associated HG B-cell NHLs arising in other anatomic locations (data not published). In this case, we have conclusively demonstrated the presence of EBV genome by two highly sensitive meth-
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY
Vdsquez-Piheiro et al. 145
Volume 84, Number 2
ods. Currently, the actual role of EBV in the histogenesis of AIDS-associated NHL is uncertain, although it could be relevant because of its frequent clonal presence in all the histologic reported subtypes. 5 In summary, we present a primary oral HG large-cell HIV-associated lymphoma with unusual morphologic and immunohistochemical features. Insofar as these features appear to be novel findings, cases such as this one deserve to be closely investigated in the future. REFERENCES 1. Epstein JB, Silvermau S Jr. Head and neck malignancies associated with HIV infection. Oral Surg Oral Med Oral Pathol 1992;73:193-200. 2. Scully C, Laskaris G, Pindborg I, Porter SR, Reichart R Oral manifestations of HIV infection and their management. I. More common lesions. Oral Surg Oral Med Oral Pathol 1991;71:158-66. 3. Ahmed T, Wonnser GR Stahl RE, et al. Malignant lymphomas in a population at risk for acquired immune deficiency syndrome. Cancer 1987;60:719-23. 4. Kristal AR, Nasca PC, Burnett WS, Miki J. Changes in the epidemiology of non-Hodgkin's lymphoma associated with epidemic Human Immunodeficiency Virus (HIV) infection. Am J Epidemiol 1988;128:711-8. 5. Raphael MM, Audouin J, Lamine M, Delecluse HI, Vuillaume M, Lenoir GM, et al. Immunophenotypic and genotypic analysis of acquired immunodeficiency syndrome-related nonHodgkin's lymphomas. Correlation with histologic features in 36 cases. French Study Group of Pathology for HIV-Associated Tumors. Am J Clin Pathol 1994;101:773-82. 6. Beral V, Peterman T, Berkelman R, Jaffe H. AIDS-associated non-Hodgkin lymphoma. Lancet 1991;337:805-9. 7. Lowenthal DA, Strauss DJ, Campbell SW, et al. AIDS-related lymphoid neoplasia. The Memorial Hospital experience. Cancer 1988;61:2325-37. 8. Hamilton-Dutoit SJ, Pallesen G, Franzmann MB, et al. AIDSrelated lymphoma. Histopathology, immunophenotype, and association with Epstein-Barr virus as demonstrated by in situ nucleic acid hybridization. Am J Pathol 1991; 138:149-63. 9. Green TL, Eversole LR. Oral lymphomas in HIV-infected patients: association with Epstein-Barr virus DNA. Oral Surg 1989;67:437-42. 10. Kaugars GE, Burns JC. Non-Hodgkin's lymphoma of the oral cavity associated with AIDS. Oral Surg Oral Med Oral Pathol 1989;67:433-6. 11. Rubin MM, Gatta CA, Cozzi GM. Non Hodgkin's lymphoma of the buccal gingiva as the initial manifestation of AIDS. J Oral Maxillofae Surg 1989;47:1311-3. 12. Howell RE, et al. Extranodal oral lymphoma. Part 2. Relationship between clinical features and the Lukes-Collins classification of 34 cases. Oral Surg Oral Med Oral Pathol 1987;64:597-602. 13. Eisenbud L, et al. Oral presentations in non-Hodgkin's lymphoma: a review of 31 cases. Oral Surg Oral Med Oral Pathol 1983;56:151-6. 14. Hashimoto N, Kurihara K. Pathological characteristics of oral lymphomas. J Oral Pathol 1982;11:214-9. 15. Slootweg PJ, Wittkampf ARM, Kluin PM, Wilde PCM, Van Unnik JAM. Extranodal non Hodgkin's Iymphoma of the oral tissues. J Maxillofac Surg 1985;13:85-92. 16. Hicks MJ, Flaitz C, Nichols CM, Luna MA, Gresik V. Intraoral presentation of anaplastic large-cell Ki-1 lymphoma in associa-
tion with HIV infection. Oral Surg Oral Med Oral Pathol 1993;76:73-81. 17. Ramirez-Amador V, Gonzalez M, De la Rosa E, et al. Oral findings in Mexican AIDS patients with cancer. J Oral Pathol Med 1993;22:87-91. 18. S6derholm AL, Lindqvist C, Heikinheimo K, et al. NonHodgkin's lymphomas presenting through oral symptoms. Int J Oral Maxillofac Surg 1990;19:131-4. 19. Langford A, Dienemann D, Schurman D, Pohle HD, Pauli G, Stein H, et al. Oral manifestations of AIDS-associated non-Hodgkin's lymphomas. Int J Oral Maxillofac Surg 1991;20:136-41. 20. Colmenero C, Gamallo G, Pintado V, et al. AIDS-related lymphoma of the oral cavity. Int J Oral Maxillofacial Surg 1991;20:2-6. 21. Molinari JA. Oral manifestations of HIV infection. J Mich Dent Assoc 1992;74:38-43. 22. Dodd CL, Greenspan D, Schiodt M, Daniels TE, Beckstead JH, MacPhall LA, et al. Unusual oral presentation of non-Hodgkin's lymphoma in association with HIV infection. Oral Surg Oral Med Oral Pathol 1992;73:603-8. 23. Shiboski CH, Hilton IF, Greenspan D, Westenhouse JL, Derish R Vranizan K, et al. HIV-related oral manifestations in two cohorts of women in San Francisco. J Acquir Immune Defic Syndr Hum Retrovirol 1994;7:964-71. 24. Men~rguez J, Mollejo M, Carri6n R, et al. Waldeyer ring lymphomas. A clinicopathologic study of 79 cases. Histopathology 1994;24:13-22. 25. 1993 Revised CDC HIV Classification System and Expanded AIDS Surveillance Definition for Adolescents and Adults. MMWR 1992;41:RR-17. 26. Preciado MV, De Matteo E, Diez B, MenN'guez J, Grinstein S. Presence of Epstein-Ban virus (EBV) and strain assignment in Argentine childhood Hodgkin's Disease. Blood 1995;86:39229. 27. Harnly ME, Swan SH, Holly EA, et al. Temporal trends in the incidence of Non-Hodgkin's lymphoma and selected malignancies in a population with a high incidence of acquired immunodeficiency syndrome (AIDS). Am J Epidemiol 1988;128:261-7. 28. Nash JR, Rothery GA, Willat DJ, Rugman F, Stell P. NonHodgkin's lymphoma of the head and neck: prognosis factors. Clin Otolaryngol 1987;12:203-10. 29. Ziegler JL, Drew WL, Miner RL, et al. Outbreak of Burkitt's lymphoma in homosexual men. Lancet 1982;2:631-3. 30. Lozada-Nur E de Sanz S, Silverman S, Miranda C, Regezi JA. Intraoral non-Hodgkin's lymphoma in seven patients with acquired immunodeficiency syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1996;82:173-8. 31. Ficarra G, Eversole LE. HI¥-related tumors of the oral cavity. Crit Rev Oral Biol Med 1994;5:159-85. 32. Carbone A, Vaccher E, Barzan L, Gloghini A, Volpe R, DeRe V. Head and neck lymphomas associated with human immunodeficiency virus infection. Arch Otolaryngol Head Neck Surg 1995;121:210-8. 33. Chadburn A, Cesarman E, Jagirdar J, Subar M, Mir R, Knowles DM. CD30 (ki-1) positive anaplastic large cell lymphoma in individuals infected with the human immunodeficiency virus. Cancer 1993;72:3078-90.
Reprint requests: Teresa V~izquez-Pifieiro,MD Servicio de Estomatologfa Hospital General Universitario Gregorio Marafi6n Dr. Esquerdo 46 28807 Madrid Spain
ORAL MEDICINE
Editors: Jed Jacobson and Margot Van Dis
HIV-Associated oral pleomorphic B-cell malignant lymphoma Teresa V~izquez-Pifieiro, PhD, MD, a Lourdes Viana de Frfas, MD, b Eva Crist6bal, PhD, c Jaime Cosfn, PhD, MD, d and Javier MenArguez, MD, PhD, e Madrid, Spain HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAIq0N
A 48-year-old HIV-seropositive homosexual patient presented with an ulcerative lesion in the left side of the soft palate, extensively involving local soft tissue structures. On histologic evaluation the lesion appeared to be a large-cell high-grade B-cell pleomorphic lymphoma with anaplastic and plasmacytoid features harboring Epstein-Barr virus genome in the tumor cells. Although known to be associated With HIV infection, this is a rare subtype of a malignant lymphoma arising in a patient positive for HIV. lfs meaning is yet unknown in biologic and prognostic terms. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod
1997;84:142-5)
Non-Hodgkin's lymphoma (NHL) is the second most c o m m o n malignancy associated with HIV infection. Its incidence is rapidly increasing, 1-3 with reports of occurrence in from 3% to 10% of patients with AIDS. 4-6 HIV-associated N H L s d e v e l o p most frequently in intravenous drug abusers. 3, 7, 8 Although approximately 70% of these are B-cell lesions, 20% are derived from T cells. In most cases, they are high-grade (HG) tumors and belong to a reduced number of histologic subtypes.5, 6 In approximately 5% of the cases, the presenting lesion is in the oral cavity, often resembling a less morbid process, z, 9-24 We report an unusual type of B-cell HG N H L arising in the oral cavity and discuss its clinical and histologic features.
CASE REPORT A 48-year-old homosexual man was admitted to the Department of Infectious Diseases of the Gregorio Marafi6n Hospital in May 1994 because of odyn0phagia occurring in the past 5 months. He also reported left pharyngeal pain radiating to the face and ear and homolateral nasal obstruction. HIV seropositivity had been discovered in 1987. Since then relapsing genital herpes and oral aphthae, gonococcal nreaDepartment of Oral Medicine. bDepartment of Oral Medicine. CDepartment of Pathology. aDepartment of Clinical Microbiology. eDepartment of Pathology. Partially supported by a grant from the Fondo de Investigaciones Sanitarias FIS 93/0016-05. Received for publication July 24, 1996; revised Sept. 27, 1996; accepted Feb. 6, 1997. Copyright © 1997 by Mosby-Year Book, Inc. 1079-2104/97/$5.00 + 0 7/13/81171
142
thritis, oral candidiasis, and cytomegalovirus retinitis had been diagnosed. He had been under treatment with AZT (500 mg/day) since 1989 and with dideoxiinosina (400 rag/day) since 1993. He was considered to be at C3 stage according to the Revised Centers for Disease Control HIV Classification System. 25 Peripheral CD4+ blood counts were less than 25 cells/mm3. Oral examination disclosed a deep nonbleeding 3 cm ulcer in the left soft palate. The ulcer showed coarse margins and necrotic areas and was covered by a yellowish fibrinous exudate. The lesion partially destroyed the left soft palate and pharyngeal pillars, sparing the uvulae and posterior soft palatine edge (Fig. 1). Radiographs did not disclose dental or osseous involvement. A craniofacial computed tomography scan confirmed the presence of an extensive lesion involving the oropharynx and infiltrating the contralateral structures through the palate including the parapharyngeal space, internal pterygoid muscle, and local adipose tissues. The nasal fossae were occupied by polypoid lesions. The left maxillary sinus was obliterated, and erosion of the superior and posterior wall could be observed (Fig. 2). After two incisional biopsies were performed, a diagnosis of diffuse HG anaplastic large-cell B-cell lymphoma (ALCL) with plasmacytoid differentiation was established. Angiocentric areas and a striking zonal pattern were seen. Although plasmacytoid differentiation was easily observed in areas, in others the tumor showed predominantly anaplastic cytologic characteristics, lmmunohistochemical techniques disclosed CD20 positivity and cytoplasmic l¢-immunoglobulin light chain restriction in the areas with plasmacytic differentiation. The predominantly anaplastic areas were positive for CD30 (Ki-1) and negative for the other two markers (Fig. 3). The presence of Epstein-Barr virus (EBV) genome could be demonstrated in the biopsy specimens with the aid of
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY Volume 84, Number 2
Vdsquez-Piheiro et al. 143
Fig. 1. Uvulae and posterior soft palatine edge are intact.
Fig. 2. Craniofacial computed tomography scan. A, Coronal computed tomography disclosed soft tissue mass occupying left nasal fossae and left maxillary sinus. B, Axial computed tomography reveals tumoral mass in palatine tonsil occupying oropharyngeal space.
polymerase chain reaction and three different sets of primers targeting different regions of the EBV genome.26 This finding was confirmed by in situ hybridization for Epstein-Ban" encoded RNA. 26 By this last technique we were able to specifically pinpoint the signal within the neoplastic ele-
ments. Attempts to isolate any microorganisms from biopsy were unsuccessful. After the staging of the tumor was completed, no additional neoplastic locations could be demonstrated. In May 1994 a first round of polychemotherapy (cyclophosphamide, adri-
144 Vdzquez-Piffeiro et al.
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY August 1997
Fig. 3. In situ hybridization for Epstein-Barr encoded RNA. Lymphomatous infiltrates involving minor salivary glands. Although positiv e signals (dark brown nuclei, big arrowhead) are frequently present in neoplastic cells, epithelial cells are constantly negative (small arrowhead). (Hematoxylin-eosin counterstaining; original magnification x40.)
amycin, vincristine, and prednisone) was started. The patient had neutropenia and septicemia with Staphylococcus aureus shortly after the second cycle was started; the patient died.
DISCUSSION It has been repeatedly shown that HIV infection and the subsequent immunosuppression results in an increased risk of malignant d i s e a s e s Although 40% of patients with AIDS have a malignant tumor at the time of the initial diagnosis, in one series the percentage increased up to 70% over the course of the disease. 4 Head and neck NHLs originate mainly in cervical lymph nodes and Waldeyer's Ring structures, including palatine tonsils and nasopharynx, z4,zs Primary oral NHLs were rare before the AIDS era, constituting only 4% to 5% of extranodal NHLs. 11-15,28 Of these tumors, approximately 20% to 32% originated in the palate, ~2,13 and only 35% of the cases showed osseous involvement.~ 1,12These tumors were almost exclusively B-cell lesions corresponding to centroblastic, diffuse histiocytic, and immunoblastic histologic subtypes) 4A5 Taken as a whole, AIDS-associated NHLs tend to be aggressive, extranodal, HG tumors frequently involving the central nervous system, bone marrow, and the gastrointestinal tract. 8,16,17 The vast majority of them (97%) are HG B-cell tumors and can be classified as Burkitt-like, immunoblastic, and centroblastic subtypes. 2°,29 HG tumors follow a very aggressive course
with a poor prognosis and a high mortality rate. Currently, the median survival of patients with AIDS-related lymphomas following treatment is 5 to 11 months. 9-11,3°32 Intraoral HIV-associated lymphomas have been reported to arise in the palate, retromolar area, gingiva, tongue, tonsils, mandible, maxillary sinus, and alveolar ridges. 19 In this patient, the tumor was located in the palatine tonsil with involvement of the maxillary sinus, nasal fossae, and oropharynx, without extension into adjacent bone. ALCLs are infrequently associated with HIV infection. 33 Although known to arise in extranodal locations, only recently HIV-related ALCL has been described to originate in the oral cavity. 16 Compared with other ALCLs, this case showed a striking morphologic and immunohistochemical variability in immunoglobulin light chain and CD30 antigen expression. These features are unusual in conventional anaplastic large-cell lymphomas. We have not been able to find previous reports of other related tumors disclosing these features in the oral cavity. In our experience this peculiar morphology and immunohistochemistry appears to be a common finding in several AIDS-associated HG B-cell NHLs arising in other anatomic locations (data not published). In this case, we have conclusively demonstrated the presence of EBV genome by two highly sensitive meth-
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY
Vdsquez-Piheiro et al. 145
Volume 84, Number 2
ods. Currently, the actual role of EBV in the histogenesis of AIDS-associated NHL is uncertain, although it could be relevant because of its frequent clonal presence in all the histologic reported subtypes. 5 In summary, we present a primary oral HG large-cell HIV-associated lymphoma with unusual morphologic and immunohistochemical features. Insofar as these features appear to be novel findings, cases such as this one deserve to be closely investigated in the future. REFERENCES 1. Epstein JB, Silvermau S Jr. Head and neck malignancies associated with HIV infection. Oral Surg Oral Med Oral Pathol 1992;73:193-200. 2. Scully C, Laskaris G, Pindborg I, Porter SR, Reichart R Oral manifestations of HIV infection and their management. I. More common lesions. Oral Surg Oral Med Oral Pathol 1991;71:158-66. 3. Ahmed T, Wonnser GR Stahl RE, et al. Malignant lymphomas in a population at risk for acquired immune deficiency syndrome. Cancer 1987;60:719-23. 4. Kristal AR, Nasca PC, Burnett WS, Miki J. Changes in the epidemiology of non-Hodgkin's lymphoma associated with epidemic Human Immunodeficiency Virus (HIV) infection. Am J Epidemiol 1988;128:711-8. 5. Raphael MM, Audouin J, Lamine M, Delecluse HI, Vuillaume M, Lenoir GM, et al. Immunophenotypic and genotypic analysis of acquired immunodeficiency syndrome-related nonHodgkin's lymphomas. Correlation with histologic features in 36 cases. French Study Group of Pathology for HIV-Associated Tumors. Am J Clin Pathol 1994;101:773-82. 6. Beral V, Peterman T, Berkelman R, Jaffe H. AIDS-associated non-Hodgkin lymphoma. Lancet 1991;337:805-9. 7. Lowenthal DA, Strauss DJ, Campbell SW, et al. AIDS-related lymphoid neoplasia. The Memorial Hospital experience. Cancer 1988;61:2325-37. 8. Hamilton-Dutoit SJ, Pallesen G, Franzmann MB, et al. AIDSrelated lymphoma. Histopathology, immunophenotype, and association with Epstein-Barr virus as demonstrated by in situ nucleic acid hybridization. Am J Pathol 1991; 138:149-63. 9. Green TL, Eversole LR. Oral lymphomas in HIV-infected patients: association with Epstein-Barr virus DNA. Oral Surg 1989;67:437-42. 10. Kaugars GE, Burns JC. Non-Hodgkin's lymphoma of the oral cavity associated with AIDS. Oral Surg Oral Med Oral Pathol 1989;67:433-6. 11. Rubin MM, Gatta CA, Cozzi GM. Non Hodgkin's lymphoma of the buccal gingiva as the initial manifestation of AIDS. J Oral Maxillofae Surg 1989;47:1311-3. 12. Howell RE, et al. Extranodal oral lymphoma. Part 2. Relationship between clinical features and the Lukes-Collins classification of 34 cases. Oral Surg Oral Med Oral Pathol 1987;64:597-602. 13. Eisenbud L, et al. Oral presentations in non-Hodgkin's lymphoma: a review of 31 cases. Oral Surg Oral Med Oral Pathol 1983;56:151-6. 14. Hashimoto N, Kurihara K. Pathological characteristics of oral lymphomas. J Oral Pathol 1982;11:214-9. 15. Slootweg PJ, Wittkampf ARM, Kluin PM, Wilde PCM, Van Unnik JAM. Extranodal non Hodgkin's Iymphoma of the oral tissues. J Maxillofac Surg 1985;13:85-92. 16. Hicks MJ, Flaitz C, Nichols CM, Luna MA, Gresik V. Intraoral presentation of anaplastic large-cell Ki-1 lymphoma in associa-
tion with HIV infection. Oral Surg Oral Med Oral Pathol 1993;76:73-81. 17. Ramirez-Amador V, Gonzalez M, De la Rosa E, et al. Oral findings in Mexican AIDS patients with cancer. J Oral Pathol Med 1993;22:87-91. 18. S6derholm AL, Lindqvist C, Heikinheimo K, et al. NonHodgkin's lymphomas presenting through oral symptoms. Int J Oral Maxillofac Surg 1990;19:131-4. 19. Langford A, Dienemann D, Schurman D, Pohle HD, Pauli G, Stein H, et al. Oral manifestations of AIDS-associated non-Hodgkin's lymphomas. Int J Oral Maxillofac Surg 1991;20:136-41. 20. Colmenero C, Gamallo G, Pintado V, et al. AIDS-related lymphoma of the oral cavity. Int J Oral Maxillofacial Surg 1991;20:2-6. 21. Molinari JA. Oral manifestations of HIV infection. J Mich Dent Assoc 1992;74:38-43. 22. Dodd CL, Greenspan D, Schiodt M, Daniels TE, Beckstead JH, MacPhall LA, et al. Unusual oral presentation of non-Hodgkin's lymphoma in association with HIV infection. Oral Surg Oral Med Oral Pathol 1992;73:603-8. 23. Shiboski CH, Hilton IF, Greenspan D, Westenhouse JL, Derish R Vranizan K, et al. HIV-related oral manifestations in two cohorts of women in San Francisco. J Acquir Immune Defic Syndr Hum Retrovirol 1994;7:964-71. 24. Men~rguez J, Mollejo M, Carri6n R, et al. Waldeyer ring lymphomas. A clinicopathologic study of 79 cases. Histopathology 1994;24:13-22. 25. 1993 Revised CDC HIV Classification System and Expanded AIDS Surveillance Definition for Adolescents and Adults. MMWR 1992;41:RR-17. 26. Preciado MV, De Matteo E, Diez B, MenN'guez J, Grinstein S. Presence of Epstein-Ban virus (EBV) and strain assignment in Argentine childhood Hodgkin's Disease. Blood 1995;86:39229. 27. Harnly ME, Swan SH, Holly EA, et al. Temporal trends in the incidence of Non-Hodgkin's lymphoma and selected malignancies in a population with a high incidence of acquired immunodeficiency syndrome (AIDS). Am J Epidemiol 1988;128:261-7. 28. Nash JR, Rothery GA, Willat DJ, Rugman F, Stell P. NonHodgkin's lymphoma of the head and neck: prognosis factors. Clin Otolaryngol 1987;12:203-10. 29. Ziegler JL, Drew WL, Miner RL, et al. Outbreak of Burkitt's lymphoma in homosexual men. Lancet 1982;2:631-3. 30. Lozada-Nur E de Sanz S, Silverman S, Miranda C, Regezi JA. Intraoral non-Hodgkin's lymphoma in seven patients with acquired immunodeficiency syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1996;82:173-8. 31. Ficarra G, Eversole LE. HI¥-related tumors of the oral cavity. Crit Rev Oral Biol Med 1994;5:159-85. 32. Carbone A, Vaccher E, Barzan L, Gloghini A, Volpe R, DeRe V. Head and neck lymphomas associated with human immunodeficiency virus infection. Arch Otolaryngol Head Neck Surg 1995;121:210-8. 33. Chadburn A, Cesarman E, Jagirdar J, Subar M, Mir R, Knowles DM. CD30 (ki-1) positive anaplastic large cell lymphoma in individuals infected with the human immunodeficiency virus. Cancer 1993;72:3078-90.
Reprint requests: Teresa V~izquez-Pifieiro,MD Servicio de Estomatologfa Hospital General Universitario Gregorio Marafi6n Dr. Esquerdo 46 28807 Madrid Spain