Bilateral conjunctival extranodal marginal zone B-cell lymphoma

Extranodal marginal zone B-cell lymphomas (EMZLs), while relatively common in adults, are rare entities in the pediatric population. A subclass of the typically aggressive non-Hodgkin lymphomas, the few reported pediatric cases indicate that, as in adults, these tumors tend to be indolent. We present a case of EMZL arising in the conjunctivae in a 9-year-old male with bilateral disease. The patient was treated with surgical excision alone and has remained disease-free 6 years after the operation.     

Rare non‐Hodgkin lymphoma of childhood and adolescence: A consensus diagnostic and therapeutic approach to pediatric‐type follicular lymphoma,marginal zone lymphoma,and nonanaplastic peripheral T‐cell lymphoma

Pediatric‐type follicular (PTFL), marginal zone (MZL), and peripheral T‐cell lymphoma (PTCL) account each for <2% of childhood non‐Hodgkin lymphoma. We present clinical and histopathological features of PTFL, MZL, and few subtypes of PTCL and provide treatment recommendations. For localized PTFL and MZL, watchful waiting after complete resection is the therapy of choice. For PTCL, therapy is subtype‐dependent and ranges from a block‐like anaplastic large cell lymphoma (ALCL)‐derived and, alternatively, leukemia‐derived therapy in PTCL not otherwise specified and subcutaneous panniculitis‐like T‐cell lymphoma to a block‐like mature B‐NHL‐derived or, preferentially, ALCL‐derived treatment followed by hematopoietic stem cell transplantation in first remission in hepatosplenic and angioimmunoblastic T‐cell lymphoma.     

Children and adolescents with marginal zone lymphoma have an excellent prognosis with limited chemotherapy or a watch‐and‐wait strategy after complete resection

Data on management of pediatric marginal zone lymphoma (MZL) are scarce. This retrospective study assessed characteristics and outcome in 66 patients who were <18 years old. Forty‐four (67%) had an extranodal MZL (EMZL), 21 (32%) a nodal MZL (NMZL), and one patient a splenic MZL. Thirty‐three patients (50%) received a variable combination of adjuvant chemotherapy/immunotherapy/radiotherapy, while the remainder, including 20 of 21 with NMZL, entered an active observation period. Overall survival was excellent (98 ± 2%), although 11 patients relapsed (17%; NMZL, n = 1; EMZL, n = 10), seven after any therapy and four after complete resection only. In conclusion, outcome of NZML, in particular, seems to be excellent after (in)complete resection and observation only.     

Anti-CD20 monoclonal antibody (rituximab) for therapy of CD20-positive nodular lymphocyte-predominant Hodgkin lymphoma in an 10-year-old girl

Biologic treatments including antibody-based therapies are still in early-phase development in Hodgkin lymphoma. The authors present the case of a 10-year-old girl with massive, solid, unilateral cervical, nodular lymphocyte-predominant Hodgkin lymphoma. Chemotherapy (doxorubicin, bleomycin, vinblastine, and dacarbazine [ABVD]) and radiotherapy were given, according to the Italian Association of Pediatric Hematology and Oncology (AIEOP) MH-96 study protocol, but the patient failed to enter complete remission. Soon after, 6 intravenous infusions of the chimeric anti-CD20 monoclonal antibody rituximab 375 mg/m² were administered, resulting in complete remission. The patients is still in continuous complete remission for 2 years. Novel therapies, such as rituximab, may be useful for children with CD20⁺ nodular lymphocyte-predominant Hodgkin lymphoma. To the authors' knowledge, this is the first report of CD20⁺ nodular lymphocyte-predominant Hodgkin lymphoma treated with rituximab in children. Further controlled trials and long-term outcome studies are warranted to define its clinical application and to improve the care of patients.     

Bone marrow minimal disseminated disease (MDD) and minimal residual disease (MRD) in childhood T‐cell lymphoblastic lymphoma stage III,detected by flow cytometry (FC) and real‐time quantitative polymerase chain reaction (RQ‐PCR)

Background

Despite overlapping features of T‐cell lymphoblastic lymphoma (T‐LLy) and T‐cell acute lymphoblastic leukemia (T‐ALL), which respond favorably to T‐ALL treatment, clinical and biological differences exist. We retrospectively assessed the prevalence of submicroscopic bone marrow (BM) minimal disseminated disease (MDD) at diagnosis and the early response to treatment (minimal residual disease—MRD) and their prognostic significance in 17 children with stage III T‐LLy treated according to Berlin‐Frankfurt‐Munster (BFM) non‐Hodgkin lymphoma protocols.

Procedure

Four‐color flow cytometry (FC) was used for lymphoma associated immunophenotype and real‐time quantitative polymerase chain reaction (RQ‐PCR) for T‐cell receptor (TCR β/δ/γ) gene rearrangements with at least 0.01% sensitivity.

Results

Two markers per patient were identified in all cases using FC and in 80% using RQ‐PCR. BM MDD at diagnosis of ≥0.01% was detected by FC and RQ‐PCR in 88% and 80% of patients, respectively, and by at least one of the methods in all patients. A significant correlation was achieved between the methods by Pearson correlation analysis (P = 0.004). MRD levels significantly decreased to very low levels on day 33 in 9 out of 10 patients studied. The only patient that remained positive relapsed.

Conclusions

MDD was prevalent in stage III T‐LLy, for which we could not prove a prognostic significance in the context of ALL‐like treatment. This study shows that both FC and RQ‐PCR methods are efficient for MDD and MRD analyses in T‐LLy. Pediatr Blood Cancer 2009;52:20–25. © 2008 Wiley‐Liss, Inc.     

Increase in T cells bearing the gamma/delta receptor associated with lymphoproliferative disease of granular lymphocytes in an infant with intractable diarrhea

A two-year-old infant with intractable diarrhea and lymphoproliferative disease of granular lymphocytes attributed to a persistent cytomegalovirus infection showed an increase in cells bearing the gamma/delta T-cell receptor (TCR), which accounted for approximately 20% of total peripheral blood lymphocytes and 40% of CD3+ T cells. Of the gamma/delta TCR+ cells, two-thirds were double negative (CD4–/CD8–) and the other one-third CD8 positive. The majority of gamma/ delta + cells were delta TCS 1 positive. The predominance of delta TCS 1 positive cells was also confirmed on biopsy of lymphoid tissues from the colon. After improvement of watery diarrhea and malnutrition following three-month hyperalimentation, the number of gamma/delta TCR+ cells decreased. The patient subsequently died of pneumonia at the age of 2 years and 11 months. A possible site-specific role for the gamma/delta TCR + cells, particularly delta TCS 1 + cells, in the human intestine is discussed.     

A newly recognized point mutation in the cytochrome b558 heavy chain gene replacing alanine57 by glutamic acid,in a patient with cytochrome b positive X-linked chronic granulomatous disease

Molecular genetic analysis was performed in a patient with cytochrome b positive X-linked chronic granulomatous disease. A previous Southern blot study, using a cytochrome b heavy chain cDNA as probe, revealed a Pst I restriction fragment pattern for the cytochrome b heavy chain gene (CYBB) different to that of normal individuals. Since restriction length polymorphism with Pst I has never been observed in control individuals and no abnormal restriction fragment patterns in the patient's CYBB was detected with seven other enzymes used, we focussed on the single Pst I site in the CYBB cDNA as being the only mutation site responsible for his disease. A fragment of the patient's cDNA which included the Pst I site was amplified by reverse polymerase chain reaction, and loss of the Pst I site in the fragment was confirmed by incubation with Pst I. Subsequent sequence analysis of the fragment revealed a point mutation in the Pst I site (cytosine to adenine), substituting glutamic acid for alanine at position 57.     

Systemic mastocytosis associated with t(8;21) acute myeloid leukemia in a child: Detection of the D816A mutation of KIT

Systemic mastocytosis (SM) associated with t(8;21) acute myeloid leukemia (AML) is very rare, and the D816 mutation of the KIT gene has previously been detected only in adult patients. We herein report the case of a 5‐year‐old female presenting with AML harboring t(8;21)(q22;q22). Her AML was refractory to chemotherapy, and bone marrow mastocytosis developed simultaneously at the initial diagnosis and during chemotherapy. The D816A mutation of KIT was detected. SM associated with t(8;21) AML, accompanied by a KIT mutation in children may result in a poor prognosis, despite the fact that t(8;21) AML are generally considered to have a favorable risk. Pediatr Blood Cancer 2012; 59: 1313–1316. © 2012 Wiley Periodicals, Inc.