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Pathology International 2014; 64: 588–590
doi:10.1111/pin.12212
Letter to the Editor Plasmablastic lymphoma of the maxillary sinus with intraoral manifestation caused by direct alveolar bone infiltration in an HIV-negative patient To the Editor: Plasmablastic lymphoma (PBL) of the oral cavity was first described by Delecluse et al. in 1997 as a new entity of a form of non-Hodgkin lymphoma (NHL) associated with human immunodeficiency virus (HIV) infection.1 They reported a series of sixteen highly malignant diffuse large B-cell lymphomas of the oral cavity with unique immunohistologic features. All their cases displayed morphologic features of diffuse large-cell lymphomas, but strikingly differed from them in that they showed minimal or absent expression of the leukocyte common antigen (CD45) as well as B-cell antigen CD20.1 Alternatively, the tumor cells showed constant expression of the characteristic plasma cell antigens (VS38c and CD38), frequent expression of CD79a, variable expression of cytoplasmic immunoglobulins and monoclonal rearrangement of the immunoglobulin heavy chain gene.1 PBL has been listed in the 2008 World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues as a non-Hodgkin B-cell lymphoma occurring predominantly in HIV-positive patients.2 PBLs account for approximately 2.6% of all HIV-related NHL.3 Here, we present a case of PBL of the maxillary sinus with intraoral manifestation caused by direct alveolar bone infiltration in an HIV-negative patient. A 50-year-old female had been treated with endodontologic management for spontaneous pain and increase of mobility of the left second molar of the maxilla for two months prior to tooth extraction, and thereafter, wound healing failed to occur. The patient was admitted to the Dental Hospital of Showa University for referral to oral surgery. On examination, a gingival ulcer, 15 × 12 mm in size, was found in the extraction site of the left second molar of the maxilla. Laboratory findings showed increases in lactate dehydrogenase (262 U/L), creatinine kinase (380 U/L) and γ-glutamic transferase (97 U/L), and revealed high thymol turbidity test (7.2 U). Complete blood count and differential peripheral white blood cell count were normal. All other laboratory data examined were within normal ranges. Computed tomography (CT) detected a lesion, 40 × 35 × 50 mm in size, occupying the left maxillary sinus, which partially destroyed the medial and posterior walls of the maxillary sinus, and *Correspondence: Tarou Irié, e-mail: [email protected] Disclosure: No conflict of interest declared. †Contributed equally to this work.
extended into the nasal cavity with permeated pattern without definite central necrosis (Fig. 1a). Further, this lesion pressed against the left orbital floor, directly infiltrated into the alveolar bone of the left maxillary molar region, and caused intraoral manifestation (Fig. 1b). Nodal involvements were suggested in the left submandibular and cervical lymph nodes from diagnostic imaging. The patient had no history of autoimmune and lymphomatous diseases. There was no evidence of immunosuppression. Biopsy was performed from the gingival ulcer which showed that the lesion was composed of diffuse and cohesive monotonous proliferation of large atypical lymphoid cells with immunoblastic or plasmablastic features (Fig. 1c,d). The nuclei were usually oval with prominent nucleoli. Only a few plasmacytic-like differentiations were identified. Apoptotic cells and mitotic figures were frequently observed. A few tingible body macrophages were sporadically present. Immunohistochemically, the atypical lymphoid cells were positive for CD45 and partially positive for CD79a, but negative for CD20 (L26) (Fig. 2b) and PAX5. Regarding the expression of plasma cell-associated antigens in the atypical lymphoid cells, CD138 was sporadically positive and VS38c (Fig. 2a) was diffusely positive. These cells were also positive for MUM-1, and focally positive for EMA and CD30. Proliferation rate as assessed by Ki-67 staining was more than 90% (Fig. 2c). Definite immunoglobulin light chain restriction was not detected by assessment for immunoglobulin kappa and lambda light chain antibodies. In situ hybridization showed positivity for Epstein-Barr virusencoded RNA (EBER) (Fig. 2d). The atypical lymphoid cells were negative for Bcl2, Bcl6, Cyclin D1, CD3, CD5, UCHL-1, CD8, CD56, TIA-1, Granzyme B and HHV8 LNA. The diagnosis of PBL was made. The patient was referred to the Department of Hematology at another hospital for further examination and treatment. No other organ and bone marrow involvement was identified, and the patient was evaluated as Stage II (Ann Arbor staging system). Serological screening was negative for hepatitis B virus, hepatitis C virus and HIV. The patient was treated with four cycles of chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) and has been in complete remission. Recent examination of this patient at 9 months after chemotherapy showed no evidence of recurrence. To date, there have been four cases reported of PBL primarily arising in the maxillary sinus with HIV negativity, including the present case.4–6 Their ages ranged from 24 to 86 years, with a mean age of 51 years, and male-to-female ratio of 1:1. One patient died of disease at 4 months after diagnosis, while the other patients were all alive for more
© 2014 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd
Letter to the Editor
589
Figure 1 CT images sliced at the level of the maxillary sinus. (a) Axial and (b) coronal views. (c,d) Photomicrographs of the biopsy. (a) The left maxillary sinus was occupied by the lesion, which partially destroyed the medial and posterior walls (arrow) of the maxillary sinus, and extended into the nasal cavity (arrowhead). (b) The lesion showed direct infiltration into the alveolar bone (arrow) of the left maxillary molar region and caused intraoral manifestation. (c) HE section shows diffuse proliferation of atypical lymphoid cells with bone resorption. (d) The large atypical lymphoid cells with immunoblastic or plasmablastic features showed cohesive monotonous proliferation.
Figure 2 (a–c) Immunohistochemical features and (d) EBER in situ hybridization of the biopsy. (a) VS38c (b) CD20 (c) Ki-67 and (d) strong EBER expression are shown in the nuclei of the atypical lymphoid cells.
than 6 months, and in one case of favorable outcome, the patient was alive more than 4 years. All four cases of PBL were EBV-positive. In a review by Dorwal et al. on extraoral PBL, they reported 31 HIV-negative patients, among whom 11 (35%) were EBVpositive.7 It was reported that EBV positivity in both oral and extraoral PBL patients who were HIV-negative was 54%, whereas that in HIV-positive patients was 74%.8 Thus, it is
noteworthy that all four cases of PBL primarily arising in the maxillary sinus with HIV negativity including our present case were EBV-positive.4–6 In this context, Waldeyer’s ring is a common EBV reservoir, and EBV-positive extranodal lymphoma of head and neck occurs at preferential sites, which in order of frequency are tonsil (36%), nose and paranasal sinus (24%), nasopharynx (20%), oropharynx (12%) and oral cavity (8%).9 Accordingly, it seems likely that high infection
© 2014 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd
590
Letter to the Editor
rate of EBV in PBL primarily arising from the maxillary sinus in HIV-negative patients is caused by regional predisposition. Therefore, EBV infection might be directly responsible for the development of maxillary sinus PBL in these patients. Additionally, persistent chronic inflammation, such as maxillary empyema, may be involved in its pathogenesis as well as that of other body cavity lymphomas, like pyothoraxassociated lymphoma.10 In conclusion, we present here, a case of PBL of the maxillary sinus with intraoral manifestation caused by direct alveolar bone infiltration in an HIV-negative patient. Further, evidence shows that EBV infection may be a major risk factor for PBL of the maxillary sinus in HIV-negative patients. Rika Yasuhara,1† Tarou Irié,1†* Eisuke Shiozawa,2 Toshiko Yamochi,2 Junichi Tanaka,1 Yohko Kohno,1 Mamiko Fujikura,3 Yukinori Kimura,3 Tomomi Hanazawa,3 Kenji Seki,3 Tsukasa Sano,3 Tatsuo Shirota,4 Miki Kushima,5 Masafumi Takimoto2 and Kenji Mishima1 1
Division of Pathology and 3Division of Radiology, Department of Oral Diagnostic Sciences, 4Department of Oral and Maxillofacial Surgery, School of Dentistry, 2 Department of Pathology, School of Medicine, Showa University and 5Department of Pathology, Showa University Koto Toyosu Hospital, Tokyo, Japan
2 Swerdlow SH, Campo E, Harris NL et al. WHO Classification of Tumours of Haematopoetic and Lymphoid Tissues, 4th edn. Lyon: International Agency for Research on Cancer (IARC), 2008. 3 Carbone A. AIDS-related non-Hodgkin’s lymphomas: From pathology and molecular pathogenesis to treatment. Hum Pathol 2002; 33: 392–404. 4 Nguyen DD, Loo BW Jr, Tillman G et al. Plasmablastic lymphoma presenting in a human immunodeficiency virus-negative patient: A case report. Ann Hematol 2003; 82: 521–5. 5 Colomo L, Loong F, Rives S et al. Diffuse large B-cell lymphomas with plasmablastic differentiation represent a heterogeneous group of disease entities. Am J Surg Pathol 2004; 28: 736–47. 6 Saraceni C, Agostino N, Cornfield DB, Gupta R. Plasmablastic lymphoma of the maxillary sinus in an HIV-negative patient: A case report and literature review. Springerplus 2013; 2: 142. 7 Dorwal P, Sachdev R, Mishra P et al. Extraoral plasmablastic lymphoma detected using ascitic fluid cytology and flow cytometry: A case report with a review of the literature. Acta Cytol 2014; 58: 309–17. 8 Castillo J, Pantanowitz L, Dezube BJ. HIV-associated plasmablastic lymphoma: Lessons learned from 112 published cases. Am J Hematol 2008; 83: 804–9. 9 Bahnassy AA, Zekri AR, Asaad N et al. Epstein-Barr viral infection in extranodal lymphoma of the head and neck: Correlation with prognosis and response to treatment. Histopathology 2006; 48: 516–28. 10 Aozasa K. Pyothorax-associated lymphoma. J Clin Exp Hematop 2006; 46: 5–10.
REFERENCES 1 Delecluse HJ, Anagnostopoulos I, Dallenbach F et al. Plasmablastic lymphomas of the oral cavity: A new entity associated with the human immunodeficiency virus infection. Blood 1997; 89: 1413–20.
© 2014 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd
Pathology International 2014; 64: 588–590
doi:10.1111/pin.12212
Letter to the Editor Plasmablastic lymphoma of the maxillary sinus with intraoral manifestation caused by direct alveolar bone infiltration in an HIV-negative patient To the Editor: Plasmablastic lymphoma (PBL) of the oral cavity was first described by Delecluse et al. in 1997 as a new entity of a form of non-Hodgkin lymphoma (NHL) associated with human immunodeficiency virus (HIV) infection.1 They reported a series of sixteen highly malignant diffuse large B-cell lymphomas of the oral cavity with unique immunohistologic features. All their cases displayed morphologic features of diffuse large-cell lymphomas, but strikingly differed from them in that they showed minimal or absent expression of the leukocyte common antigen (CD45) as well as B-cell antigen CD20.1 Alternatively, the tumor cells showed constant expression of the characteristic plasma cell antigens (VS38c and CD38), frequent expression of CD79a, variable expression of cytoplasmic immunoglobulins and monoclonal rearrangement of the immunoglobulin heavy chain gene.1 PBL has been listed in the 2008 World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues as a non-Hodgkin B-cell lymphoma occurring predominantly in HIV-positive patients.2 PBLs account for approximately 2.6% of all HIV-related NHL.3 Here, we present a case of PBL of the maxillary sinus with intraoral manifestation caused by direct alveolar bone infiltration in an HIV-negative patient. A 50-year-old female had been treated with endodontologic management for spontaneous pain and increase of mobility of the left second molar of the maxilla for two months prior to tooth extraction, and thereafter, wound healing failed to occur. The patient was admitted to the Dental Hospital of Showa University for referral to oral surgery. On examination, a gingival ulcer, 15 × 12 mm in size, was found in the extraction site of the left second molar of the maxilla. Laboratory findings showed increases in lactate dehydrogenase (262 U/L), creatinine kinase (380 U/L) and γ-glutamic transferase (97 U/L), and revealed high thymol turbidity test (7.2 U). Complete blood count and differential peripheral white blood cell count were normal. All other laboratory data examined were within normal ranges. Computed tomography (CT) detected a lesion, 40 × 35 × 50 mm in size, occupying the left maxillary sinus, which partially destroyed the medial and posterior walls of the maxillary sinus, and *Correspondence: Tarou Irié, e-mail: [email protected] Disclosure: No conflict of interest declared. †Contributed equally to this work.
extended into the nasal cavity with permeated pattern without definite central necrosis (Fig. 1a). Further, this lesion pressed against the left orbital floor, directly infiltrated into the alveolar bone of the left maxillary molar region, and caused intraoral manifestation (Fig. 1b). Nodal involvements were suggested in the left submandibular and cervical lymph nodes from diagnostic imaging. The patient had no history of autoimmune and lymphomatous diseases. There was no evidence of immunosuppression. Biopsy was performed from the gingival ulcer which showed that the lesion was composed of diffuse and cohesive monotonous proliferation of large atypical lymphoid cells with immunoblastic or plasmablastic features (Fig. 1c,d). The nuclei were usually oval with prominent nucleoli. Only a few plasmacytic-like differentiations were identified. Apoptotic cells and mitotic figures were frequently observed. A few tingible body macrophages were sporadically present. Immunohistochemically, the atypical lymphoid cells were positive for CD45 and partially positive for CD79a, but negative for CD20 (L26) (Fig. 2b) and PAX5. Regarding the expression of plasma cell-associated antigens in the atypical lymphoid cells, CD138 was sporadically positive and VS38c (Fig. 2a) was diffusely positive. These cells were also positive for MUM-1, and focally positive for EMA and CD30. Proliferation rate as assessed by Ki-67 staining was more than 90% (Fig. 2c). Definite immunoglobulin light chain restriction was not detected by assessment for immunoglobulin kappa and lambda light chain antibodies. In situ hybridization showed positivity for Epstein-Barr virusencoded RNA (EBER) (Fig. 2d). The atypical lymphoid cells were negative for Bcl2, Bcl6, Cyclin D1, CD3, CD5, UCHL-1, CD8, CD56, TIA-1, Granzyme B and HHV8 LNA. The diagnosis of PBL was made. The patient was referred to the Department of Hematology at another hospital for further examination and treatment. No other organ and bone marrow involvement was identified, and the patient was evaluated as Stage II (Ann Arbor staging system). Serological screening was negative for hepatitis B virus, hepatitis C virus and HIV. The patient was treated with four cycles of chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) and has been in complete remission. Recent examination of this patient at 9 months after chemotherapy showed no evidence of recurrence. To date, there have been four cases reported of PBL primarily arising in the maxillary sinus with HIV negativity, including the present case.4–6 Their ages ranged from 24 to 86 years, with a mean age of 51 years, and male-to-female ratio of 1:1. One patient died of disease at 4 months after diagnosis, while the other patients were all alive for more
© 2014 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd
Letter to the Editor
589
Figure 1 CT images sliced at the level of the maxillary sinus. (a) Axial and (b) coronal views. (c,d) Photomicrographs of the biopsy. (a) The left maxillary sinus was occupied by the lesion, which partially destroyed the medial and posterior walls (arrow) of the maxillary sinus, and extended into the nasal cavity (arrowhead). (b) The lesion showed direct infiltration into the alveolar bone (arrow) of the left maxillary molar region and caused intraoral manifestation. (c) HE section shows diffuse proliferation of atypical lymphoid cells with bone resorption. (d) The large atypical lymphoid cells with immunoblastic or plasmablastic features showed cohesive monotonous proliferation.
Figure 2 (a–c) Immunohistochemical features and (d) EBER in situ hybridization of the biopsy. (a) VS38c (b) CD20 (c) Ki-67 and (d) strong EBER expression are shown in the nuclei of the atypical lymphoid cells.
than 6 months, and in one case of favorable outcome, the patient was alive more than 4 years. All four cases of PBL were EBV-positive. In a review by Dorwal et al. on extraoral PBL, they reported 31 HIV-negative patients, among whom 11 (35%) were EBVpositive.7 It was reported that EBV positivity in both oral and extraoral PBL patients who were HIV-negative was 54%, whereas that in HIV-positive patients was 74%.8 Thus, it is
noteworthy that all four cases of PBL primarily arising in the maxillary sinus with HIV negativity including our present case were EBV-positive.4–6 In this context, Waldeyer’s ring is a common EBV reservoir, and EBV-positive extranodal lymphoma of head and neck occurs at preferential sites, which in order of frequency are tonsil (36%), nose and paranasal sinus (24%), nasopharynx (20%), oropharynx (12%) and oral cavity (8%).9 Accordingly, it seems likely that high infection
© 2014 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd
590
Letter to the Editor
rate of EBV in PBL primarily arising from the maxillary sinus in HIV-negative patients is caused by regional predisposition. Therefore, EBV infection might be directly responsible for the development of maxillary sinus PBL in these patients. Additionally, persistent chronic inflammation, such as maxillary empyema, may be involved in its pathogenesis as well as that of other body cavity lymphomas, like pyothoraxassociated lymphoma.10 In conclusion, we present here, a case of PBL of the maxillary sinus with intraoral manifestation caused by direct alveolar bone infiltration in an HIV-negative patient. Further, evidence shows that EBV infection may be a major risk factor for PBL of the maxillary sinus in HIV-negative patients. Rika Yasuhara,1† Tarou Irié,1†* Eisuke Shiozawa,2 Toshiko Yamochi,2 Junichi Tanaka,1 Yohko Kohno,1 Mamiko Fujikura,3 Yukinori Kimura,3 Tomomi Hanazawa,3 Kenji Seki,3 Tsukasa Sano,3 Tatsuo Shirota,4 Miki Kushima,5 Masafumi Takimoto2 and Kenji Mishima1 1
Division of Pathology and 3Division of Radiology, Department of Oral Diagnostic Sciences, 4Department of Oral and Maxillofacial Surgery, School of Dentistry, 2 Department of Pathology, School of Medicine, Showa University and 5Department of Pathology, Showa University Koto Toyosu Hospital, Tokyo, Japan
2 Swerdlow SH, Campo E, Harris NL et al. WHO Classification of Tumours of Haematopoetic and Lymphoid Tissues, 4th edn. Lyon: International Agency for Research on Cancer (IARC), 2008. 3 Carbone A. AIDS-related non-Hodgkin’s lymphomas: From pathology and molecular pathogenesis to treatment. Hum Pathol 2002; 33: 392–404. 4 Nguyen DD, Loo BW Jr, Tillman G et al. Plasmablastic lymphoma presenting in a human immunodeficiency virus-negative patient: A case report. Ann Hematol 2003; 82: 521–5. 5 Colomo L, Loong F, Rives S et al. Diffuse large B-cell lymphomas with plasmablastic differentiation represent a heterogeneous group of disease entities. Am J Surg Pathol 2004; 28: 736–47. 6 Saraceni C, Agostino N, Cornfield DB, Gupta R. Plasmablastic lymphoma of the maxillary sinus in an HIV-negative patient: A case report and literature review. Springerplus 2013; 2: 142. 7 Dorwal P, Sachdev R, Mishra P et al. Extraoral plasmablastic lymphoma detected using ascitic fluid cytology and flow cytometry: A case report with a review of the literature. Acta Cytol 2014; 58: 309–17. 8 Castillo J, Pantanowitz L, Dezube BJ. HIV-associated plasmablastic lymphoma: Lessons learned from 112 published cases. Am J Hematol 2008; 83: 804–9. 9 Bahnassy AA, Zekri AR, Asaad N et al. Epstein-Barr viral infection in extranodal lymphoma of the head and neck: Correlation with prognosis and response to treatment. Histopathology 2006; 48: 516–28. 10 Aozasa K. Pyothorax-associated lymphoma. J Clin Exp Hematop 2006; 46: 5–10.
REFERENCES 1 Delecluse HJ, Anagnostopoulos I, Dallenbach F et al. Plasmablastic lymphomas of the oral cavity: A new entity associated with the human immunodeficiency virus infection. Blood 1997; 89: 1413–20.
© 2014 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd
