Sinusoidal CD30+ diffuse large B‐cell lymphoma can masquerade as anaplastic large cell lymphoma in pediatric posttransplant lymphoproliferative disorders

Posttransplant lymphoproliferative disorder (PTLD) is a known complication of solid organ transplantation. Diffuse large B‐cell lymphoma (DLBCL) is frequently seen in this setting. However, CD30+ DLBCL with sinusoidal pattern of involvement has not been reported in pediatric PTLD. We are reporting a 9‐year‐old female child presented with diffuse lymphadenopathy postheart transplantation. The pattern of involvement was suggestive of anaplastic large cell lymphoma, but the malignant cells were positive for B‐cell markers and negative for anaplastic lymphoma kinase. The patient was treated aggressively with multiagent chemotherapy and rituximab. Accurate diagnosis in PTLD is paramount in making management decisions.     

PRIMARY CUTANEOUS ANAPLASTIC LARGE CELL LYMPHOMA

Anaplastic large cell lymphoma (ALCL) is characterized by proliferation of anaplastic large CD 30+ T-cell lymphoid cells with abundant cytoplasm. Primary cutaneous ALCL is a rare form of ALCL, usually seen in elderly patients. In this report, the authors present an unusual case of 15-year-old boy with a solitary left ear lobe mass, previously reported as keratoacanthoma which was later histopathologically and immunohistochemically diagnosed as T-cell phenotype, anaplastic lymphoma kinase (ALK)-negative primary cutaneous anaplastic large cell lymphoma. The patient's response to chemotherapy was good and he is receiving the continuation phases of his chemotherapy.     

Clinical Features and Treatment Results of Children with Diffuse Large B-Cell Lymphoma

The demographic, clinical characteristics, and treatment groups of 33 children with diffuse large B-cell lymphoma (DLBCL) were recorded and analyzed among 1486 non-Hodgkin lymphoma (NHL) cases since 1972. The median age was 9.7 years (range 1.4–16.9) and male/female ratio was 24/9 = 2.6. Kaplan–Meier methods and logrank tests were used in treatment analysis. The frequency of DLBCL among 1486 NHL cases was 2.2%, however, the percentage was 9.3% in cases diagnosed after 2000. The event-free survival (EFS) and overall survival (OS) rates for 33 children were 61% and 65.1% at 5 years, respectively. The EFS and OS rates of low stage (stages I and II) disease decreased to lower level in advanced stage (stages III and IV) disease. Associated conditions and ages older than 14 years were found as poor prognostic factors in multivariate analysis. The survival rates in children with DLBCL need further improvement. This is mainly related with late referral of those children with advanced disease. The proper diagnosis and early referral is essential in these children for a better survival rate. The children with associated conditions and older children must be handled with care since these are found as poor prognostic factors.     

Isolated cutaneous anaplastic large cell lymphoma progressing to severe systemic disease with myocardial involvement and central nervous system infiltration

Anaplastic large cell lymphoma (ALCL) is a rare tumor comprising around 10-15% of childhood lymphomas. We describe the case of a female who initially presented with localized skin disease associated with an insect bite. However, she subsequently relapsed with widespread systemic ALK-positive ALCL that included lymphoma deposits in the myocardium, a very rare manifestation. Her disease responded well to chemotherapy but she later developed a fatal relapse in the CNS. We also present data on an immune response to ALK, demonstrating a fluctuation in the levels of circulating antibodies to ALK corresponding to the different phases of her illness.     

High-Risk ALK Negative Anaplastic Large-Cell Lymphoma Presenting with Hypereosinophilic Syndrome in a 2.5-Year-Old Child

The hypereosinophilic syndromes (HES) are characterized by prolonged nonreactive peripheral blood hypereosinophilia with tissue damage. The lymphocytic HES variant can precede malignant clonal T-cell disease in adults but it is extremely rare to be the presenting feature of lymphomas in children. Here we present a 2.5-year-old boy with HES and mediastinal T-cell anaplastic lymphoma kinase (ALK) negative systemic anaplastic large-cell lymphoma. Mature and immature eosinophils without blasts were shown on bone marrow aspiration while biopsy revealed malignant infiltration. The patient responded well to initial corticosteroid therapy, but high-risk features make a challenge of finding the cure in this extremely rare case.     

Treatment Outcome of Chinese Children with Anaplastic Large Cell Lymphoma by Using a Modified B-NHL-BFM-90 Protocol

Pediatric anaplastic large cell lymphoma (ALCL) has rarely been reported in Chinese pediatric patients. This study evaluated the clinical characteristics and treatment outcome of Chinese pediatric patients with ALCL. Between October 2002 and October 2012, 39 untreated pediatric patients with ALCL were enrolled at a single institution. The patients were stratified into three groups (R1, R2, and R3) based on the stage of the disease, clinical risk factors, and chemotherapeutic response, and received different intensive chemotherapy regimens based on a modified B-NHL-BFM-90 protocol. Of the 39 patients, 22 were boys, and 17 were girls, with a median age at diagnosis of 10 years (range 2–16 years), 91.2% were anaplastic lymphoma kinase (ALK)-positive. The patient groups R1, R2, and R3 accounted for 12.8%, 30.4%, and 56.4% of the total, respectively. 87.2% of patients were stage III/IV. At a median follow-up period of 52 months (range 15–136 months), seven patients relapsed and three patients died of their disease. The 5-year event-free survival for all patients was 81.4% ± 6.4%, with 100%, 83.3% ± 10% and 75.3% ± 9.8% for groups R1, R2, and R3, respectively. The overall survival for all patients was 92.2% ± 4.3%. Our study demonstrates that a risk-stratified treatment with a modified B-NHL-BFM-90 protocol is efficacious for Chinese children with ALCL.     

Lymphoblastic lymphoma: Late relapse in childhood

This report describes two children with lymphoblastic lymphoma who relapsed more than 2^1/2 years from diagnosis. Relapses occurred at seven and 20 months after completion of treatment. Their therapy consisted of an intensive pulse chemotherapy program combined with radiation therapy. Initial relapse after two years' treatment has been extremely rare in patients receiving contemporary chemotherapy programs, and two-year survival without disease has been considered a cure. These cases illustrate that late relapses can occur after intensive chemotherapy and that two-year disease-free survival must not be interpreted as a complete cure.     

儿童晚期非霍奇金淋巴瘤治疗策略探讨

目的探讨儿童晚期(Ⅲ～Ⅳ期)非霍奇金淋巴瘤(NHL)的治疗策略。方法总结1999.1～2003.1年确诊Ⅲ～Ⅳ期NHL10例,其中组织病理分型:淋巴母细胞型5例,小无裂型3例,间变型大细胞性2例。肿瘤免疫分型:B细胞6例,(Ⅲ期2例,Ⅳ期4例);T细胞性NHL4例(Ⅲ期2例,Ⅳ期2例);按不同免疫标记和肿瘤分期组合化疗方案,并观察疗效。结果①临床疗效:9/10获CR及CCR并完成全疗程停药;1/10例NR;②肿瘤分期:Ⅲ期NHL:4/4例CCR,并已经完成全疗程。Ⅳ期NHL:5/6例完成全疗程并均已停药1年以上,1例未能缓解。③免疫分型:除1/10例B细胞性(Ⅳ期)治疗无效外,其余B和T细胞共9/10例,均达理想疗效;结论强烈、联合、规范性化疗,治疗儿童晚期NHL,可以获得满意的效果。     

Anaplastic large cell lymphoma in a child presenting with cutaneous nodules and blisters

A 13-year-old girl was admitted to our hospital with a one-month history of bullous skin lesions. Physical examination revealed ulcerated and nonulcerated cutaneous plaques, bullae, enlarged cervical and supraclavicular lymph nodes and hepatomegaly. In another hospital, histopathological diagnosis of a skin biopsy was reported to be consistent with tuberculosis and she was treated with antimycobacterial drugs. Since no response was obtained, she was referred to our center after a new lymph node biopsy was obtained. At our center, histopathological diagnosis was anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL). We started LMT chemotherapy regimen and initial response was complete. Eight months after initial admisision, she experienced cutaneous recurrence of disease while on maintenance protocol. Chemotherapy was changed to LSA4 regimen. She is still on chemotherapy and has been in complete remission for nine months. Clinicians should be aware of this uncommon presentation of ALCIL, which can be confused with other diseases clinically or histologically.     

IRF4 translocation status in pediatric follicular and diffuse large B‐cell lymphoma patients enrolled in Children's Oncology Group trials

Large B‐cell lymphoma with IRF4 rearrangement is a provisional entity in the 2017 World Health Organization classification. In order to characterize these lymphomas in children from the United States, IRF4 FISH and immunohistochemical stains were performed on 32 follicular lymphoma and diffuse large B‐cell lymphoma (DLBCL) from Children's Oncology Group studies. Two DLBCLs (6%) had IRF4 rearrangements, one involving the ileocecal valve and another involving the tonsil and cerebrospinal fluid. Both cases had strong, diffuse IRF4/MUM1 immunohistochemical staining, which may be a pathologic clue to the diagnosis. Reclassification of these cases may have prognostic and therapeutic implications.     

SH2D1A基因突变的淋巴瘤患儿6例病例系列报告

背景：SH2D1A 基因突变的儿童淋巴瘤临床罕见且有其特殊的临床特征及疾病预后。 目的：总结伴SH2D1A基因突变的儿童淋巴瘤临床表现、病理特点、治疗方案和预后。 设计：病例系列报告。 方法：纳入2017年6月至 2022年7月于首都医科大学附属儿童医院（我院）初诊为淋巴瘤且年龄＜18岁,经高通量全外显子基因测序提示SH2D1A 基因突变的连续住院病例。根据病理诊断确定治疗方案：侵袭性成熟B细胞淋巴瘤基于改良的LMB89方案治疗;成熟T细胞淋巴瘤合并家族性噬血细胞综合征（HLH）患儿先以HLH方案控制病情,确诊后予SMILE方案化疗。化疗2~3个月行中期疗效评估。化疗结束后3个月评估超声和PET/CT,化疗结束第1、2年内每3个月评估瘤灶超声、肝功能、LDH和免疫功能。 主要结局指标：SH2D1A基因突变淋巴瘤患儿的临床特征和预后。 结果6例伴SH2D1A基因突变淋巴瘤患儿,均为男性;中位发病年龄5（4~12）岁。瘤灶累及胃肠道3例,中枢神经系统、头颈部和多脏器浸润各1例;临床分期：Ⅱ期1例,Ⅲ期3例,Ⅳ期2例;病理类型：3例弥漫大B细胞淋巴瘤,1例高级别成熟B细胞淋巴瘤,1例伴11q异常的伯基特样淋巴瘤,1例儿童系统性EB病毒阳性T细胞淋巴瘤。5例患儿体液免疫和/或细胞免疫指标下降。5例病初全血和血浆EBV DNA均阴性,其中2例病程中复测全血EBV DNA上升至≥105拷贝数/mL;1例病初合并HLH,多次全血EBV DNA为106拷贝数/mL。6例均提示SH2D1A基因突变,2例完善SAP蛋白检测未见异常;1例染色体异常。3例完成化疗,2例因HLH死亡,1例予利妥昔单抗免疫治疗。 结论：SH2D1A基因突变的淋巴瘤患儿临床少见,病理形态多表现为非霍奇金淋巴瘤（成熟B细胞淋巴瘤）,预后较差,在合适时机考虑行异基因造血干细胞移植可改善疾病预后。     

儿童纵隔起源非霍奇金淋巴瘤36例回顾分析

目的 总结分析儿童纵隔起源非霍奇金淋巴瘤(NHL)的临床特征和预后.方法 回顾性分析1999年5月1日至2007年8月31日收治的36例原发于纵隔的NHL患儿的临床特点、病理分型、诊断、治疗方法和预后.结果 27例经纵隔肿块或外周淋巴结活检通过病理形态、免疫组化确诊,其中24例为淋巴母细胞型,3例为间变性大细胞型;9例通过骨髓或胸水细胞学、免疫分型确诊.36例免疫表型均为T细胞型.分期诊断中,Ⅲ期24例,Ⅳ期12例;随访时间8～116个月(中位随访时间35个月);24例出现上腔静脉压迫综合征(SVCS)和气道压迫症,其中22例急症处理有效;29例(80%,29/36)达完全缓解(CR);6例复发(20%,6/29);13例死亡(36%,13/36);3年无进展生存率为61.3%(标准误8%).结论 早期诊断对降低NHL死亡率、提高长期生存率尤为重要,诱导化疗处理急症有效,根据病理分型分别采用T-Ⅲ-Ⅳ-CCCG99及T-NHL-2002和B-NHL-2001方案治疗纵隔起源淋巴瘤是可行的.     

Burkitt's lymphoma between African and American types in Turkish children: Clinical,viral (EBV), and molecular studies

Seventy-two Turkish children with Burkitt's lymphoma (BL) observed during a period of 22 years (1968–1990) have been analysed retrospectively. The diagnosis was established histologically according to WHO criteria. BL represented 50% of NHL in this series. The patients were staged according to Ziegler's system. The median age of patients was 5.5 years with a sex (M/F) ratio of 2.1/1. The most common primary site of tumor involvement was the abdomen (69.4%), which was followed by facial tumors, in particular the jaw and orbit (49.9%). There were 21 cases with jaw (29.1%) and 15 cases with orbital involvement (20.8%) at initial presentation. The majority of the patients (84.4%) were in advanced stages (C and D) at initial diagnosis. Facial tumors observed in Turkish children with BL were more similar to African Burkitt's lymphoma than American or European cases. High titers of antibodies against VCA and EA of EBV were also seen in our recent cases of BL. Two main treatment regimens, namely, single agent chemotherapy with cyclophosphamide (CYX) (1968–1974) and three drug (COM) combination chemotherapy, were used consecutively (1974–1988). COM has been shown to produce better results than single agent therapy. The clinical presentation, mean age, and high antibodies (lgG) to EBV and preliminary molecular studies revealed that BL appears to be in between African and non-African types in Turkish children. This will be further elucidated by direct examination of tumor cells for EBV and investigation of the molecular characteristics of Turkish tumors. Such studies are presently under way. © 1993 Wiley-Liss, Inc.     

Pediatric inflammatory myofibroblastic tumor: anaplastic lymphoma kinase (ALK) expression and prognosis

BACKGROUND: Pediatric inflammatory myofibroblastic tumor (IMT) is rare, with unpredictable clinical behavior. Recently, it has been associated with anaplastic lymphoma kinase (ALK) expression. METHODS: Patients under age 16, treated for IMT between 1976 and 2000 were reviewed. Mean follow-up was 8 years (range 1 month-22 years). RESULTS: Eight children had IMT, with a mean age of 6 years (range, 11 months-14 years) and female to male ratio of 3:1. Tumor location was lung (four patients), abdomen (two patients), lung and abdomen (one patient), and abdomen, head, and neck (one patient). Presenting symptoms included anemia (seven patients), fever (six patients), and dyspnea (four patients). Laboratory results included thrombocytosis (six patients), hypergammaglobulinemia (four patients), elevated sedimentation rate (four patients), and leukocytosis (three patients). Immunohistochemistry revealed ALK expression in four of eight tumors. Four children had complete resection and are alive. Two of these children had ALK-positive tumors. Four patients had incomplete resection, and two had recurrences treated successfully with resection and radiotherapy; the other two died of disease. For the incomplete resection patients, those that were ALK-positive lived, and those that were ALK-negative did not. CONCLUSIONS: Eight children were treated for IMT over a 15-year period. ALK expression was found in half the tumors. Prognosis was improved with ALK expression and complete surgical resection.     

State of the Art and Future Needs in Cytogenetic/Molecular Genetics/Arrays in childhood lymphoma: summary report of workshop at the First International Symposium on childhood and adolescent non-Hodgkin lymphoma, April 9, 2003, New York City, NY

BACKGROUND: A significant number of studies describe the cytogenetics and molecular genetics of adult non-Hodgkin lymphoma (NHL); however, similar knowledge is lacking regarding pediatric NHL. METHODS: A workshop to discuss the "State of the Art and Future Needs in Cytogenetic/Molecular Genetics/Arrays" in pediatric NHL was held in conjunction with the First International Symposium on Childhood and Adolescent Non-Hodgkin Lymphoma on April 9, 2003 in New York City. RESULTS: Cytogenetic characteristics of pediatric NHL include 14q11.2 rearrangements in T-cell lymphoblastic leukemia/lymphomas (LBL), ALK rearrangements in anaplastic large cell lymphomas (ALCL), and CMYC translocations in both Burkitt and Burkitt-like lymphomas (BL/BLL). Pediatric diffuse large B-cell lymphoma (DLBCL) is cytogenetically different from DLBCL in adults, suggesting a different disease in children. Microarray studies demonstrate three types of T-cell leukemia, the leukemic counterpart of LBL, that block T-cell differentiation at different stages of T-cell development, corresponding to LYL, TAL1, and HOX-expressing leukemias. ALCL cell lines have a unique expression profile compared to normal T-cells. Germinal centers of BL have CMYC expression signatures, indicating that CMYC expression is ectopic and does not reflect the physiology of the normal cell counterpart. CONCLUSIONS: Additional cytogenetic, molecular and microarray investigations of NHL in children are vital to better understand these diseases, their etiology, and differences from adult NHL. A greater understanding of pediatric NHL will lead to disease-specific and patient-individualized therapies of these diseases.     

PRIMARY TESTICULAR BURKITT LYMPHOMA IN A CHILD

A 13-year-old boy was referred to the authors' hospital following a right inguinal orchiectomy for a right scrotal mass. Histopathological examination revealed Burkitt lymphoma. The left testis was found to be small with heterogeneous parenchyma by scrotal ultrasound (US) and other systemic investigations were negative for lymphoma involvement. Ultrasound-guided fine-needle aspiration biopsy showed no evidence of involvement in the left testis. Considering stage I Burkitt lymphoma, chemotherapy was started. Following the first course, US findings changed: the volume of the left testis decreased and the parenchyma became homogeneous. The left testis was considered to be involved by lymphoma at initial diagnosis and chemotherapy was intensified. At the end of 5 months of chemotherapy the left testis was again heterogeneous in US. A wedge-biopsy was negative for lymphoma. The patient is under regular follow-up and is in complete remission 19 months after the end of chemotherapy. Primary testicular lymphoma is quite rare in children and experience is limited. Changes in testicular size and parenchyma by US should not necessarily indicate involvement by lymphoma in pubertal boys.     

Primary testicular Burkitt lymphoma in a child

A 13-year-old boy was referred to the authors' hospital following a right inguinal orchiectomy for a right scrotal mass. Histopathological examination revealed Burkitt lymphoma. The left testis was found to be small with heterogeneous parenchyma by scrotal ultrasound (US) and other systemic investigations were negative for lymphoma involvement. Ultrasound-guided fine-needle aspiration biopsy showed no evidence of involvement in the left testis. Considering stage I Burkitt lymphoma, chemotherapy was started. Following the first course, US findings changed: the volume of the left testis decreased and the parenchyma became homogeneous. The left testis was considered to be involved by lymphoma at initial diagnosis and chemotherapy was intensified. At the end of 5 months of chemotherapy the left testis was again heterogeneous in US. A wedge-biopsy was negative for lymphoma. The patient is under regular follow-up and is in complete remission 19 months after the end of chemotherapy. Primary testicular lymphoma is quite rare in children and experience is limited. Changes in testicular size and parenchyma by US should not necessarily indicate involvement by lymphoma in pubertal boys.     

Hypothalamic obesity syndrome: Rare presentation of CNS+ B-cell lymphoblastic lymphoma

Hypothalamic obesity syndrome can affect brain tumor patients following surgical intervention and irradiation. This syndrome is rare at diagnosis in childhood cancer, but has been reported with relapse of acute lymphoblastic leukemia. Here we present a case of hypothalamic obesity syndrome as the primary presentation of a toddler found to have CNS+ B‐cell lymphoblastic lymphoma. Cytogenetic studies on diagnostic cerebrospinal fluid revealed MLL gene rearrangement (11q23). Hyperphagia and obesity dramatically improved following induction and consolidation chemotherapy. We describe a novel presentation of hypothalamic obesity syndrome in CNS B‐cell lymphoblastic lymphoma, responsive to chemotherapy. Pediatr Blood Cancer 2012; 59: 930–933. © 2011 Wiley Periodicals, Inc.