Case Report Korean J Otorhinolaryngol-Head Neck Surg 2018;61(10): / pissn / eissn

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Case Report Korean J Otorhinolaryngol-Head Neck Surg 2018;61(10):536-40 / pissn 2092-5859 / eissn 2092-6529 https://doi.org/10.3342/kjorl-hns.2017.00073 Various Clinical Presentation of Post-Transplant Lymphoproliferative Disorder in Head and Neck: A Case Series of 3 Patients Hee-jung Kim 1, Sang Joon Choi 2, Young Hyeh Ko 2, and Nayeon Choi 1 1 Departments of Otorhinolaryngology-Head and Neck Surgery, 2 Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 다양한임상양상을보이는두경부의이식후림프증식성질환 : 3 예 김희정 1 최상준 2 고영혜 2 최나연 1 성균관대학교의과대학삼성서울병원이비인후과학교실, 1 병리학교실 2 Received January 26, 2017 Revised March 20, 2017 Accepted March 24, 2017 Address for correspondence Nayeon Choi, MD Department of Otorhinolaryngology- Head and Neck Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea Tel +82-2-3410-3579 Fax +82-2-3410-3879 E-mail chlskduschoi@naver.com The outcome of solid organ and bone marrow transplantation has been dramatically improved with the development of immunosuppressive agent. However, the use of immunosuppressive agents could increase the risk of malignancies such as post-transplant lymphoproliferative disorder (PTLD). PTLD is regarded as the lymphoid malignancy of patients using immunosuppressive agents, and it could present diverse and non-specific symptoms. It involves various organs including the tonsil, adenoid, lymph node, and the brain. Because of its poor prognosis, an early suspicion of pathologic diagnosis is crucial for the treatment of PTLD. In this report, we demonstrate the case of three pediatric patients who had been treated for PTLD of various clinical presentations by early suspicion and pathologic diagnosis. Korean J Otorhinolaryngol-Head Korean J Otorhinolaryngol-Head Neck Surg 2018;61(10):536-40 Neck Surg Key WordsZZ Head and neck ㆍ Immunosuppressive agent ㆍ Post-transplant lymphoproliferative disorder. 서 론 - This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 증례 증례 1 536 Copyright 2018 Korean Society of Otorhinolaryngology-Head and Neck Surgery

A B C D Case 3 Case 2 Case 1 E Fig. 1. Case 1. Endoscopic image showed adenoid hypertrophy (A, white arrows) and computed tomography (CT) showed enhanced lymphoid enlargement of adenoid (B, black arrows). Case 2. Nasal endoscopic image demonstrated hypertrophic adenoid with purulent discharge (C, white asterisk) and CT showed adenoid enlargement with abscess formation (D, black asterisk). Case 3. Laryngoscopic evaluation revealed hypertrophy of aryepiglottic fold (E, white arrowheads) and laryngeal soft tissue hypertrophy was suspicious on CT (F, black arrowheads). F www.kjorl.org 537

Korean J Otorhinolaryngol-Head Neck Surg 2018;61(10):536-40 로 증가하였고, 전신 마취하에서의 아데노이드 조직검사는 식을 받고 면역억제제(cyclosporin 50 mg, 1일 2회)를 복용 PTLD(T-lineage, EBV negative)로 진단되었다(Fig. 2A). 이 하였다. 이식 2개월 뒤 반복되는 목 통증 및 비루, 코골이를 에, 면역억제제를 하루 0.25 mg, 2회로 감량하고, rituximab 호소하였고, 검진상 편도 및 아데노이드 비대와 삼출(Fig. 160 mg을 1주일 간격으로 총 4회 정맥 주사하였다. 혈액 EBV 1C and D)이 관찰되었다. 혈액 EBV DNA PCR은 이식 전 음 DNA PCR은 rituximab 4회 치료 후 음전되었으며, 이후 면역 성이었으나, 64 copies/ul로 증가되었다. 림프증식성 질환이 억제제를 다시 0.5 mg으로 증량하여 생후 28개월까지 특이 소 의심되고, 반복되는 편도염과 발열이 있었기 때문에, 전신 마 견 없이 경과 관찰 중이다. 취하 양측 편도 절제술 및 아데노이드 조직검사를 시행하였 다. 조직검사에서 PTLD(B-cell lineage, polymorphic type) 증 례2 로 진단되어(Fig. 2B), rituximab 650 mg을 1주 간격으로 총 은 2 copies/ul이고, 아데노이드 조직검사는 PTLD(mono- 으로 관찰되어, 고용량 항암 치료 및 말초혈 조혈모세포 이 morphic; diffuse large B-cell lymphoma type) 소견이었다 Case 2-1 뒤, 이전과 같은 증상을 보여 시행한 검사상 EBV DNA PCR 사선 치료를 받았다. 하지만, 4개월 뒤, 후복벽 종양이 지속적 A B Case 3 soft part sarcoma)으로 항암치료 후, 종양 절제술 및 추가 방 Case 1 3회 주사하였고, 그 후 EBV DNA PCR은 음전되었다. 2개월 Case 2-2 15세 남자 환자는 후복벽에 발생한 포상 연부 육종(alveolar C D Fig. 2. Case 1 was diagnosed with T-cell lineage EBV negative post-transplant lymphoproliferative disease (PTLD). Effacement of normal tonsillar architecture by lymphoid cell proliferation (H&E stain, 200), negative for EBV-encoded RNA in situ hybridization ( 200), and positive immunohistochemical stain of CD3 and CD4 ( 200) were observed (A). Case 2-1 had pathologic diagnosis as B-cell polymorphic type PTLD. Loss of tonsillar architecture with necrosis (H&E, 40), small and large cell mixture of lymphocytes, immunoblasts and plasma cells (H&E, 200) were showed. EBV-encoded RNA in situ hybridization was positive ( 200) and EBV plus CD79a double staining showed majority of EBV-positive cells are positive for CD79a ( 200) (B). Case 2-2 had relapse PTLD which was diagnosed with PTLD of monomorphic diffuse large B-cell lymphoma. Sheets of monotonous large lymphoid cells (H&E, 200) and positive for EBV-encoded RNA in situ hybridization ( 200) were detected. CD20 ( 200, CD20) was positive and Ki-67 ( 200, Ki-67) was also positive in more than 70% of tumor cells ( 200) (C). Case 3 was diagnosed with early lesion plasmacytic hyperplasia type PTLD. Maintenance of tonsillar architecture with plasmacytic proliferation was showed (H&E, 40, 200), and EBV-encoded RNA in situ hybridization was positive in few tumor cells ( 200, EBV) (D). RNA: ribonucleic acid, EBV: Epstein-Barr virus. 538 www.kjorl.org 3

고찰 - 증례 3 - - - www.kjorl.org 539

Korean J Otorhinolaryngol-Head Neck Surg 2018;61(10):536-40 REFERENCES 1) Boubenider S, Hiesse C, Goupy C, Kriaa F, Marchand S, Charpentier B. Incidence and consequences of post-transplantation lymphoproliferative disorders. J Nephrol 1997;10(3):136-45. 2) Mynarek M, Schober T, Behrends U, Maecker-Kolhoff B. Posttransplant lymphoproliferative disease after pediatric solid organ transplantation. Clin Dev Immunol 2013;2013:814973. 3) Gottschalk S, Rooney CM, Heslop HE. Post-transplant lymphoproliferative disorders. Annu Rev Med 2005;56:29-44. 4) Webber SA, Naftel DC, Fricker FJ, Olesnevich P, Blume ED, Addonizio L, et al. Lymphoproliferative disorders after paediatric heart transplantation: a multi-institutional study. Lancet 2006;367(9506): 233-9. 5) Shroff R, Rees L. The post-transplant lymphoproliferative disorder-a literature review. Pediatr Nephrol 2004;19(4):369-77. 6) Evens AM, David KA, Helenowski I, Nelson B, Kaufman D, Kircher SM, et al. Multicenter analysis of 80 solid organ transplantation recipients with post-transplantation lymphoproliferative disease: outcomes and prognostic factors in the modern era. J Clin Oncol 2010; 28(6):1038-46. 7) Engels EA, Pfeiffer RM, Fraumeni JF Jr, Kasiske BL, Israni AK, Snyder JJ, et al. Spectrum of cancer risk among US solid organ transplant recipients. JAMA 2011;306(17):1891-901. 8) Weinstock DM, Ambrossi GG, Brennan C, Kiehn TE, Jakubowski A. Preemptive diagnosis and treatment of Epstein-Barr virusassociated post transplant lymphoproliferative disorder after hematopoietic stem cell transplant: an approach in development. Bone Marrow Transplant 2006;37(6):539-46. 9) Lim WH, Russ GR, Coates PT. Review of Epstein-Barr virus and post-transplant lymphoproliferative disorder post-solid organ transplantation. Nephrology (Carlton) 2006;11(4):355-66. 10) Starzl TE, Nalesnik MA, Porter KA, Ho M, Iwatsuki S, Griffith BP, et al. Reversibility of lymphomas and lymphoproliferative lesions developing under cyclosporin-steroid therapy. Lancet 1984;1(8377): 583-7. 11) Loren AW, Porter DL, Stadtmauer EA, Tsai DE. Post-transplant lymphoproliferative disorder: a review. Bone Marrow Transplant 2003;31(3):145-55. 12) Mucha K, Foroncewicz B, Niemczyk K, Ziarkiewicz-Wróblewska B, Stanisławek-Sut O, Zieniewicz K, et al. Tonsil enlargement after liver transplantation in adults--reason enough for tonsillectomy? Two cases of tonsillar posttransplantation lymphoproliferative disease. Liver Transpl 2007;13(6):918-23. 13) Elstrom RL, Andreadis C, Aqui NA, Ahya VN, Bloom RD, Brozena SC, et al. Treatment of PTLD with rituximab or chemotherapy. Am J Transplant 2006;6(3):569-76. 14) Nalesnik MA. The diverse pathology of post-transplant lymphoproliferative disorders: the importance of a standardized approach. Transpl Infect Dis 2001;3(2):88-96. 540