Ann Hematol DOI 10.1007/s00277-013-1935-6
LETTER TO THE EDITOR
Pulmonary lymphocyte-rich classical Hodgkin lymphoma with early response to ABVD therapy Akira Honda & Fumihiko Nakamura & Yasuhito Nannya & Yukako Shintani & Masashi Fukayama & Motoshi Ichikawa & Mineo Kurokawa
Received: 6 June 2013 / Accepted: 8 October 2013 # Springer-Verlag Berlin Heidelberg 2013
Dear Editor, Pulmonary Hodgkin lymphoma is a rare subgroup of Hodgkin lymphoma which primarily affects the lung with minimal extrapulmonary lesions [1]. The disease manifests as multiple nodules or, less frequently, as a solitary mass in the pulmonary parenchyma [2]. The histological spectrum of pulmonary Hodgkin lymphoma resembles that of nodular Hodgkin lymphoma; nodular sclerosis and mixed cellularity account for common subtypes, while lymphocyte-rich classical Hodgkin lymphoma (LRCHL) is much less frequent. A meta-analysis of 61 cases with pulmonary Hodgkin lymphoma identified only one case (2%) of LRCHL [1]. Therefore, LRCHL with primary pulmonary lesions is extremely rare. We herein describe another case of pulmonary LRCHL and discuss the optimal treatment strategy which has not yet been determined. A 35-year-old female presented with a 2-month history of progressive nonproductive cough and intermittent fever. Physical examination detected mild enlargement of a left supraclavicular node. Laboratory test results included hemoglobin level of 110 g/L and leukocyte count of 10.4× 10 9 /L. Chest radiograph was remarkable for multiple A. Honda : F. Nakamura : Y. Nannya : M. Ichikawa : M. Kurokawa (*) Department of Hematology and Oncology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan e-mail: [email protected] Y. Shintani : M. Fukayama Department of Pathology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan M. Kurokawa Department of Cell Therapy and Transplantation Medicine, The University of Tokyo Hospital, Tokyo, Japan
parenchymal nodules in both lungs (Fig. 1a). Transbronchial biopsy of a nodule did not reach a diagnosis although microscopic examination showed dominant infiltration of lymphocytes. Open biopsy of a supraclavicular node was also performed, and histopathology was notable for a vague nodular lesion with scattered binuclear large cells in the background of small- to medium-sized lymphocytes without neutrophils or eosinophils (Fig. 1b). Immunophenotype of the large cells was CD30+, CD15+ (partial), and CD20−, consistent with Reed–Sternberg (RS) cells. She was then referred to us for further scrutiny and treatment. F-18 fluorodeoxyglucose positron emission tomography (FDGPET) combined with computed tomography (CT) scan revealed uptakes in multiple pulmonary nodules, mediastinum, supraclavicular lymph nodes, hepatic hilar lymph nodes, and splenic nodules (Fig. 1c, d). There was no evidence of granulomatosis, sarcoidosis, carcinoma, or infection. Taken together, the patient was diagnosed as pulmonary LRCHL with nodal and splenic involvement. Treatment was initiated with six cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) regimen. Interim F-18 FDG-PET/CT scan after two cycles disclosed salient regression of parenchymal nodules and complete resolution of the extrapulmonary lesions (Fig. 1e, f). The patient has so far been relapse-free for 14 months. In the pre-ABVD era, pulmonary Hodgkin lymphoma was associated with relatively dismal outcomes. In one study, mechlorethamine, vincristine, procarbazine, and prednisolone (MOPP) therapy resulted in a relapse rate of 56 % (five of nine cases) [2]. This series included one case of relapsed pulmonary LRCHL. These results are partly explained by the inability to use radiotherapy for pulmonary parenchymal lesions. Our case was featured by early response of pulmonary lesions to ABVD therapy. This regimen was superior to MOPP therapy as first-line treatment
Ann Hematol Fig. 1 Pulmonary lymphocyterich classical Hodgkin lymphoma. a Chest radiograph at presentation showed multiple nodular lesions in both lungs. b Histopathology of a biopsied supraclavicular lymph node was characterized by proliferation of small- to medium-sized lymphocytes with scattered binuclear Reed–Sternberg cells (H&E stain). c F-18 FDG-PET before treatment indicated uptakes in pulmonary nodules (maximal standardized uptake values (SUVmax), 6.6), supraclavicular lymph nodes (SUVmax, 4.6), mediastinum (SUVmax, 6.3), hepatic hilar lymph nodes (SUVmax, 7.0), and splenic nodules (SUVmax, 4.1). d F-18 FDG-PET combined with CT scan before treatment revealed uptakes in multiple pulmonary nodules. e No uptakes were detected by F-18 FDG-PET after two cycles of ABVD therapy. f Marked regression of pulmonary nodules was simultaneously noted
of nodal Hodgkin lymphoma [3]. Furthermore, ABVD therapy alone yielded a better overall survival than ABVD plus radiotherapy in the treatment of limitedstage Hodgkin lymphoma [4]. It is therefore likely that ABVD or comparable regimens also improve the outcomes of pulmonary Hodgkin lymphoma even in the absence of subsequent radiotherapy. A large study is required to confirm this notion.
Conflict of interest The authors declare that they have no conflict of interest. Informed consent Informed consent was obtained from the patient.
References 1. Radin AI (1990) Primary pulmonary Hodgkin’s disease. Cancer 65(3): 550–563 2. Yousem SA, Weiss LM, Colby TV (1986) Primary pulmonary Hodgkin’s disease. A clinicopathologic study of 15 cases. Cancer 57(6):1217–1224 3. Canellos GP, Anderson JR, Propert KJ, Nissen N, Cooper MR, Henderson ES, Green MR, Gottlieb A, Peterson BA (1992) Chemotherapy of advanced Hodgkin’s disease with MOPP, ABVD, or MOPP alternating with ABVD. N Engl J Med 327(21):1478–1484 4. Meyer RM, Gospodarowicz MK, Connors JM, Pearcey RG, Wells WA, Winter JN, Horning SJ, Dar AR, Shustik C, Stewart DA, Crump M, Djurfeldt MS, Chen BE, Shepherd LE, Group NCT, Group ECO (2012) ABVD alone versus radiation-based therapy in limited-stage Hodgkin’s lymphoma. N Engl J Med 366(5):399–408
LETTER TO THE EDITOR
Pulmonary lymphocyte-rich classical Hodgkin lymphoma with early response to ABVD therapy Akira Honda & Fumihiko Nakamura & Yasuhito Nannya & Yukako Shintani & Masashi Fukayama & Motoshi Ichikawa & Mineo Kurokawa
Received: 6 June 2013 / Accepted: 8 October 2013 # Springer-Verlag Berlin Heidelberg 2013
Dear Editor, Pulmonary Hodgkin lymphoma is a rare subgroup of Hodgkin lymphoma which primarily affects the lung with minimal extrapulmonary lesions [1]. The disease manifests as multiple nodules or, less frequently, as a solitary mass in the pulmonary parenchyma [2]. The histological spectrum of pulmonary Hodgkin lymphoma resembles that of nodular Hodgkin lymphoma; nodular sclerosis and mixed cellularity account for common subtypes, while lymphocyte-rich classical Hodgkin lymphoma (LRCHL) is much less frequent. A meta-analysis of 61 cases with pulmonary Hodgkin lymphoma identified only one case (2%) of LRCHL [1]. Therefore, LRCHL with primary pulmonary lesions is extremely rare. We herein describe another case of pulmonary LRCHL and discuss the optimal treatment strategy which has not yet been determined. A 35-year-old female presented with a 2-month history of progressive nonproductive cough and intermittent fever. Physical examination detected mild enlargement of a left supraclavicular node. Laboratory test results included hemoglobin level of 110 g/L and leukocyte count of 10.4× 10 9 /L. Chest radiograph was remarkable for multiple A. Honda : F. Nakamura : Y. Nannya : M. Ichikawa : M. Kurokawa (*) Department of Hematology and Oncology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan e-mail: [email protected] Y. Shintani : M. Fukayama Department of Pathology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan M. Kurokawa Department of Cell Therapy and Transplantation Medicine, The University of Tokyo Hospital, Tokyo, Japan
parenchymal nodules in both lungs (Fig. 1a). Transbronchial biopsy of a nodule did not reach a diagnosis although microscopic examination showed dominant infiltration of lymphocytes. Open biopsy of a supraclavicular node was also performed, and histopathology was notable for a vague nodular lesion with scattered binuclear large cells in the background of small- to medium-sized lymphocytes without neutrophils or eosinophils (Fig. 1b). Immunophenotype of the large cells was CD30+, CD15+ (partial), and CD20−, consistent with Reed–Sternberg (RS) cells. She was then referred to us for further scrutiny and treatment. F-18 fluorodeoxyglucose positron emission tomography (FDGPET) combined with computed tomography (CT) scan revealed uptakes in multiple pulmonary nodules, mediastinum, supraclavicular lymph nodes, hepatic hilar lymph nodes, and splenic nodules (Fig. 1c, d). There was no evidence of granulomatosis, sarcoidosis, carcinoma, or infection. Taken together, the patient was diagnosed as pulmonary LRCHL with nodal and splenic involvement. Treatment was initiated with six cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) regimen. Interim F-18 FDG-PET/CT scan after two cycles disclosed salient regression of parenchymal nodules and complete resolution of the extrapulmonary lesions (Fig. 1e, f). The patient has so far been relapse-free for 14 months. In the pre-ABVD era, pulmonary Hodgkin lymphoma was associated with relatively dismal outcomes. In one study, mechlorethamine, vincristine, procarbazine, and prednisolone (MOPP) therapy resulted in a relapse rate of 56 % (five of nine cases) [2]. This series included one case of relapsed pulmonary LRCHL. These results are partly explained by the inability to use radiotherapy for pulmonary parenchymal lesions. Our case was featured by early response of pulmonary lesions to ABVD therapy. This regimen was superior to MOPP therapy as first-line treatment
Ann Hematol Fig. 1 Pulmonary lymphocyterich classical Hodgkin lymphoma. a Chest radiograph at presentation showed multiple nodular lesions in both lungs. b Histopathology of a biopsied supraclavicular lymph node was characterized by proliferation of small- to medium-sized lymphocytes with scattered binuclear Reed–Sternberg cells (H&E stain). c F-18 FDG-PET before treatment indicated uptakes in pulmonary nodules (maximal standardized uptake values (SUVmax), 6.6), supraclavicular lymph nodes (SUVmax, 4.6), mediastinum (SUVmax, 6.3), hepatic hilar lymph nodes (SUVmax, 7.0), and splenic nodules (SUVmax, 4.1). d F-18 FDG-PET combined with CT scan before treatment revealed uptakes in multiple pulmonary nodules. e No uptakes were detected by F-18 FDG-PET after two cycles of ABVD therapy. f Marked regression of pulmonary nodules was simultaneously noted
of nodal Hodgkin lymphoma [3]. Furthermore, ABVD therapy alone yielded a better overall survival than ABVD plus radiotherapy in the treatment of limitedstage Hodgkin lymphoma [4]. It is therefore likely that ABVD or comparable regimens also improve the outcomes of pulmonary Hodgkin lymphoma even in the absence of subsequent radiotherapy. A large study is required to confirm this notion.
Conflict of interest The authors declare that they have no conflict of interest. Informed consent Informed consent was obtained from the patient.
References 1. Radin AI (1990) Primary pulmonary Hodgkin’s disease. Cancer 65(3): 550–563 2. Yousem SA, Weiss LM, Colby TV (1986) Primary pulmonary Hodgkin’s disease. A clinicopathologic study of 15 cases. Cancer 57(6):1217–1224 3. Canellos GP, Anderson JR, Propert KJ, Nissen N, Cooper MR, Henderson ES, Green MR, Gottlieb A, Peterson BA (1992) Chemotherapy of advanced Hodgkin’s disease with MOPP, ABVD, or MOPP alternating with ABVD. N Engl J Med 327(21):1478–1484 4. Meyer RM, Gospodarowicz MK, Connors JM, Pearcey RG, Wells WA, Winter JN, Horning SJ, Dar AR, Shustik C, Stewart DA, Crump M, Djurfeldt MS, Chen BE, Shepherd LE, Group NCT, Group ECO (2012) ABVD alone versus radiation-based therapy in limited-stage Hodgkin’s lymphoma. N Engl J Med 366(5):399–408
