소아에서발생한 Blastic Plasmacytoid Dendritic Cell Neoplasm 1 예
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1 Clinical Pediatric Hematology-Oncology Volume 22 ㆍ Number 2 ㆍ October 2015 CASE REPORT 소아에서발생한 Blastic Plasmacytoid Dendritic Cell Neoplasm 1 예 박경미 1 ㆍ양유진 1 ㆍ서정호 1 ㆍ신동훈 2 ㆍ임영탁 1 부산대학교의과대학 1 소아과학교실, 2 병리학교실 A Case of Blastic Plasmacytoid Dendritic Cell Neoplasm in a Child Kyung Mi Park, M.D. 1, Eu Jeen Yang, M.D. 1, Jung Ho Seo, M.D. 1, Dong Hoon Shin, M.D. 2 and Young Tak Lim, M.D., Ph.D. 1 Departments of 1 Pediatrics and 2 Pathology, Pusan National University Children s Hospital, Yangsan, Korea Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a very rare hematological malignancy in children that is characterized by bruise-like skin lesions, with or without bone marrow involvement. Because the clinical course of BPDCN is highly aggressive and fatal in adults, allogeneic hematopoietic stem cell transplantation (HSCT) is recommended as the optimal treatment. Due to its rarity, the pediatric experience with BPDCN is limited and standard treatment has so far not been defined. We report a case of a 14-year-old boy with BPDCN involving the skin, bone marrow and lymph nodes. The patient was treated with high-risk group acute lymphoblastic leukemia protocol. He achieved a complete remission after induction chemotherapy and still maintains clinical remission without HSCT for 17 months after initial diagnosis. Key Words: Blastic plasmacytoid dendritic cell neoplasm, Children pissn / eissn Clin Pediatr Hematol Oncol 2015;22: Received on September 15, 2015 Revised on October 3, 2015 Accepted on October 6, 2015 Corresponding Author: Young Tak Lim Department of Pediatrics, Pusan National University Children s Hospital, 20 Geumo-ro, Meulgeum-eup, Yangsan 05612, Korea Tel: Fax: limyt@pusan.ac.kr Introduction Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, highly aggressive hematopoietic malignancy characterized by cutaneous and bone marrow involvement [1,2]. It was formerly known as blastic natural killer (NK) cell lymphoma and CD4+/CD56+ hematodermic neoplasm. [3,4]. BPDCN was chosen in the 2008 World Health Organization (WHO) classification, because it was derived from the plasmacytoid dendritic cell [3]. BPDCN usually occurs in elderly patients with an average age between 60 and 70 years; however it can occur at any age, even in children [2,5]. The experience in children with this disease is very limited. Single or multiple skin lesions characteristically appear, such as nodules, patches, and bruise-like lesion [6-10]. Systemic involvement often accompanies BPDCN at the bone marrow and lymph nodes [1,5,11,12]. Here, we report a case of BPDCN in an adolescent boy, who was present with the characteristic skin lesions. Case Report A 14-year-old male presented purple nodules on the 181
2 Kyung Mi Park, et al right thigh and a generalized brownish patch on the face swelling. The laboratory findings including complete blood for about one month (Fig. 1). The size of the lesion had count (CBC) showed a white blood cell count of 5,350/uL, been slowly growing, but with no tenderness. He had nei- with 38.9% of lymphocytes on differential counts, hemoglo- ther hepatosplenomegaly nor generalized lymph node bin of 14.0 g/dl, and a platelet count of 175,000/uL. There Fig. 1. (A) Brownish hyperpigmented patches on both cheek. (B) Bruise-like nodular lesion on right thigh. Fig. 2. Histopathological and immunohistochemical findings of the skin tissue. (A; H&E stain) Extensive lymphoid infiltration of the entire dermis. No epidermal involvement is demonstrated. Immunohistochemical stainings of LCA (B), CD56 (C) and TdT (D) are positive (brown staining). 182 Vol. 22, No. 2, October 2015
3 BPDCN in a Child were no blast cells on a peripheral blood smear. Blood chemistry was normal except for a slightly elevated LDH level (474 IU/L). Skin biopsy of the facial patch showed medium sized tumor cells mainly infiltrating periadnexal areas sparing the epidermis (Fig. 2). These cells had finely dispersed chromatin with inconspicuous nucleoli and were positive for common leukocyte antigen (LCA), TdT and CD56, and negative for pancytokeratin, vimentin, MPO, CD68, CD7, CD5, CD3, CD45RO, and CD20 (Fig. 2). Additional immunohistochemical stains for CD4, CD8 and CD123 were performed. Tumor cells were faintly positive for CD4, CD123 and negative for CD8. In situ hybridization for Epstein-Barr (EB) virus-encoded early RNAs were negative. The bone marrow aspiration and biopsy showed normocellular marrow, but a single abnormal aggregate with relatively large immature lymphoid cells was noted. Immunohistochemical stains revealed that the cells were positive for CD56 and CD4, whereas negative for CD3 and CD8 (Fig. 3). A positron emission tomography scan showed increased uptake in the right axillary lymph node, both inguinal lymph nodes and the right external iliac lymph node (Fig. 4). With these findings, he was diagnosed with BPDCN involving skin, bone marrow, and lymph nodes. After diagnosis, treatment with Children s Cancer Group (CCG)-1961 acute lymphoblastic leukemia (ALL) protocol was initiated. Induction chemotherapy consisted of vincristine, prednisone, doxorubicin and L-asparaginase. The cutaneous lesions and palpable nodule on the thigh rapidly decreased in size after one week of chemotherapy. Complete remission (CR) of bone marrow was achieved after 1-month of induction chemotherapy. He received consolidation chemotherapy with cyclophosphamide, 6-mercaptopurine, cytosine arabinoside, and methotrexate for 5 weeks, and was further administered maintenance chemotherapy of 6-mercaptopurine, methotrexate, vincrisitine, and prednisolone. To this date, he remains in complete remission without evidence of relapse for 17 months on maintenance chemotherapy. Discussion BPDCN is a rare and clinically aggressive hematopoietic precursor cell malignancy that represented by characteristic skin lesions, with or without bone marrow involvement [1-3,5,12]. It was formerly described as blastic NK cell lymphoma or agranular CD4+ CD56+ hematodermic neoplasm/ tumor [3,4]. The current nomenclature, BPDCN, was classi- Fig. 4. A positron emission tomography scan shows involvement of right axillary lymph nodes (white arrowhead) and both inguinal lymph nodes (white arrow). Fig. 3. Histopathological and immunohistochemical findings of the bone marrow. (A; H&E stain) Abnormal proliferation of lymphoblastoid cells are show. The results of immunochemical staining in bone marrow tissue showed for CD4 (B) and CD56 (C) are positive (brown staining). Clin Pediatr Hematol Oncol 183
4 Kyung Mi Park, et al fied under acute myeloid leukemia (AML) and related precursor neoplasms in the 2008 WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues [1-3]. The immunophenotype and gene expression of BPDCN show that this neoplasm is derived from the precursor of plamacytoid dendritic cells [5]. BPDCN usually occurs in older adults with a median age of 65 years and more often in males [1]. It can present itself at any age, even in children, but this disease is very rare in children [2,5]. BPDCN is often presented with characteristic skin lesions, such as nodules, plaques, or bruise-like lesions that can be associated with erythema, hyperpigmentation, purpura, or ulceration [3-8,12,13]. Approximately 85% of patients with BPDCN show signs of cutaneous lesions, and there is a favorable outcome in treatment of patients without cutaneous lesions [5,11,13]. Extracutaneous involvement of bone marrow, lymph nodes or blood appears often in 60 percent of cases [5,14]. Our patient in this case presented multiple skin lesions with bone marrow and lymph nodes involvement. Biopsy of skin lesions typically shows diffuse infiltration of medium-sized blast cells in the dermis sparing the epidermis, and blast cells have irregular nuclei, fine chromatin, and at least 1 small nucleolus [1,2,5]. The diagnosis of BPDCN relies on the Immunophenotypic features of the malignant cells. The tumor cells commonly express CD4, CD56, CD123, and TCL1. However, B cell antigens (CD19, CD20), T cell antigens (CD3, CD5), and CD34 are not expressed [1]. CD123 is most commonly thought of as the specific marker of BPDCN; however, 4.4% negative rate was reported by Cota et al [15]. In situ hybridization for EB virus-encoded early RNAs is not detected in BPDCN associated with nasal type extranodal NK/T cell lymphoma. Genetic abnormalities in BPDCN also have been identified by cytogenetic studies, array-based comparative genomic hybridization, gene expression profiling, next-generation sequencing, and whole-exome sequencing [1,2]. Due to its rarity and only recent recognition as a distinct clinicopathological entity, the experience on pediatric BPDCN is especially limited and standard treatment has not been defined yet. A variety of regimens have been employed in the treatment of BPDCN; ALL-type or lymphoma-type chemotherapies have been most commonly utilized and ALLtype chemotherapies are associated with the best reported results [1,5]. Because relapse occurs within a year after leukemia-type chemotherapy of BPDCN in adults, adult patients usually receive high-dose chemotherapy followed by hematopoietic stem cell transplantation (HSCT) at the first CR [4,12]. In contrast to the rapidly fatal outcome typically observed in adults with BPDCN, pediatric patients of BPDCN may have a better prognosis than adult patients. HSCT did not increase the overall survival in children [5]. Therefore, in pediatric patients with BPDCN, HSCT can be reserved as a secondary treatment in patients who failed to CR or relapsed after induction chemotherapy. [1,5,6]. In our case, the patient had CR after ALL-type induction chemotherapy and still remained in CR without HSCT for 17 months after initial diagnosis. In BPDCN, cutaneous involvement was commonly considered as an unfavorable prognostic factor and a slightly higher percentage in pediatric cases reported the lack of cutaneous involvement at presentation compared in adults [5,11,13]. The basis for the apparent disparity in clinical behavior between adult and pediatric cases is not certain. Although the immunophenotype profiles are quite similar between pediatric and adult cases, S-100 expression was detected in 75% of pediatric cases but in only 25% of adult cases. Despite this, the functional significance of S-100 positivity in BPDCN is uncertain [5]. For pediatric BPDCN, further study on larger number of cases is needed to better define prognostic factors, optimal treatment strategies, and especially the role of HSCT in pediatric patients on first complete remission after chemotherapy. Acknowledgements This study was supported by a 2014 research grant from Pusan National University Yangsan Hospital. References 1. Riaz W, Zhang L, Horna P, Sokol L. Blastic plasmacytoid dendritic cell neoplasm: update on molecular biology, diagnosis, 184 Vol. 22, No. 2, October 2015
5 BPDCN in a Child and therapy. Cancer Control 2014;21: Shi Y, Wang E. Blastic plasmacytoid dendritic cell neoplasm: a clinicopathologic review. Arch Pathol Lab Med 2014;138: Lim MS, de Leval L, Quintanilla-Martinez L. Commentary on the 2008 WHO classification of mature T- and NK-cell neoplasms. J Hematop 2009;2: Petrella T, Bagot M, Willemze R, et al. Blastic NK-cell lymphomas (agranular CD4+CD56+ hematodermic neoplasms): a review. Am J Clin Pathol 2005;123: Jegalian AG, Buxbaum NP, Facchetti F, et al. Blastic plasmacytoid dendritic cell neoplasm in children: diagnostic features and clinical implications. Haematologica 2010;95: Nomura H, Egami S, Kasai H, et al. Blastic plasmacytoid dendritic cell neoplasm in a 7-year-old girl with a solitary skin lesion mimicking traumatic purpura. Acta Derm Venereol 2015;95: Chang SE, Choi HJ, Huh J, et al. A case of primary cutaneous CD56+, TdT+, CD4+, blastic NK-cell lymphoma in a 19- year-old woman. Am J Dermatopathol 2002;24: Eguaras AV, Lo RW, Veloso JD, Tan VG, Enriquez ML, Del Rosario ML. CD4+/CD56+ hematodermic neoplasm: blastic NK cell lymphoma in a 6-year-old child: report of a case and review of literature. J Pediatr Hematol Oncol 2007;29: Dharmani PA, Mittal NM, Subramanian PG, et al. Blastic plasmacytoid dendritic cell neoplasm: report of two pediatric cases. Indian J Pathol Microbiol 2015;58: Park SS, Kim MJ, Kim MB, Lee CH, Lim YT. A case of blastic NK cell lymphoma in children. Clin Pediatr Hematol Oncol 2008;15: Zhong XD, Wang LZ, Wang X, et al. Diffuse lung metastases in a child with blastic plasmacytoid dendritic cell neoplasm and review. Eur J Pediatr 2014;173: Prochaska L, Dakhil C, Mathur S. Blastic plasmacytoid dendritic cell neoplasm: A rapidly progressive and fatal disease without aggressive intervention. Clin Med Insights Case Rep 2013;6: Rauh MJ, Rahman F, Good D, et al. Blastic plasmacytoid dendritic cell neoplasm with leukemic presentation, lacking cutaneous involvement: Case series and literature review. Leuk Res 2012;36: Julia F, Petrella T, Beylot-Barry M, et al. Blastic plasmacytoid dendritic cell neoplasm: clinical features in 90 patients. Br J Dermatol 2013;169: Cota C, Vale E, Viana I, et al. Cutaneous manifestations of blastic plasmacytoid dendritic cell neoplasm-morphologic and phenotypic variability in a series of 33 patients. Am J Surg Pathol 2010;34: Clin Pediatr Hematol Oncol 185
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