Clinical Outcomes of Extracranial Germ Cell Tumors: A Single Institute’s Experience

Objective: To determine the clinical features and treatment outcomes of pediatric extracranial germ cell tumor (EGCT) in Thailand. Materials and methods: A retrospective chart review of children under 15 years old with newly diagnosed EGCT who were treated at Faculty of Medicine Siriraj Hospital from January, 2004 to December, 2013 was conducted. Results: Forty-four patients were included in the study. The median age at diagnosis was 1.74 years (1 day-14.7 years) with the median follow up time of 6.9 years (14 days-15.2 years). Twenty-eight patients (64%) had extragonadal tumor. The most common primary tumor location was the sacrococcygeal area. Majority of the patients (61%) had malignant EGCT; yolk sac tumor was the most common diagnosis. Six patients (14%) had stage IV disease. Forty patients (91%) underwent surgery; 27 patients (61%) received chemotherapy. Thirty-eight patients (86%) achieved remission; 3 patients (7%) subsequently relapsed at a median time of 1 year. Eight patients (18%) died, mostly from tumor progression. The 5-year event-free survival (EFS) and overall survival (OS) rate were 78.3% and 81.1%, respectively. Patients achieving total tumor removal had significantly better 5-year EFS and OS. Cox regression analysis revealed that the adequacy of surgery was the only prognostic factor for survival. Conclusion: The survival rate of pediatric EGCT in our study was relatively favorable, but still inferior to that of developed countries. Novel therapy may be warranted for those patients who are unresponsive to the current treatment

OUTCOMES OF OVERT AND NON-OVERT DISSEMINATED INTRAVASCULAR COAGULATION USING THE ISTH DIC SCORING SYSTEM IN CHILDREN: A SINGLE-CENTER STUDY

Background: Several disseminated intravascular coagulation (DIC) scoring systems are used for prognosticating the clinical outcomes of patients with DIC. However, research on children is scarce. This study compared the clinical outcomes of overt and non-overt DIC using the International Society on Thrombosis and Hemostasis (ISTH) DIC scoring system. Methods: This retrospective study reviewed data on children aged 1 month to 15 years diagnosed with DIC between 2003 and 2014. Results: Of 244 patients, 179 (73.4%) had overt DIC, and 65 (26.6%) had non-overt DIC. The most common causes were infection (84.8%), tissue injury (7%), and malignancies (2.9%). The 28-day case fatality rate was significantly higher for overt than non-overt DIC (76% vs 15.6%; P < 0.001). DIC scores were significantly associated with mortality (R2 = 0.89). Each clinical parameter (platelet count, prothrombin time, and fibrin degradation products) was associated with mortality (P = 0.01). On multivariable analysis, the factors associated with death were platelet counts ≤ 50 000 cells/mm3 (OR, 2.42; 95% CI, 1.08–5.42; P = 0.031); overt DIC score (OR, 7.62; 95% CI, 2.94–19.75; P < 0.001); renal dysfunction (OR, 2.92; 95% CI, 1.34–6.37; P = 0.007); shock (OR, 39.62; 95% CI, 4.99–314.84; P = 0.001); and acute respiratory distress syndrome (OR, 25.90; 95% CI, 3.12–214.80; P = 0.003). Conclusions: The 28-day case-fatality rate was significantly higher for patients with overt than non-overt DIC and concordant with ISTH scores. ISTH DIC scores can be used as a clinical predictor for DIC in children

Germline <i>HAVCR2</i> mutations and their relation to the clinical spectrum of subcutaneous panniculitis-like T-cell lymphoma and hemophagocytic lymphohistiocytosis: results from a multicenter study and meta-analysis

Germline HAVCR2 mutations are frequently detected in subcutaneous panniculitis-like T-cell lymphoma (SPTCL) patients with/without hemophagocytic lymphohistiocytosis (HLH) but factors associated with variable manifestations remain undetermined. To evaluate clinical variations and associated factors in SPTCL and/or HLH with/without HAVCR2 mutations, we performed direct sequencing of HAVCR2 exon 2 using DNA from patients with SPTCL or idiopathic HLH/HLH-like systemic illnesses, defined by HLH alone without secondary causes. The systematic review and individual patient data (IPD) level meta-analysis which included the present and previously published studies reporting HAVCR2 mutations in SPTCL with/without HLH populations was subsequently conducted using random-effects meta-analysis and multivariate logistic regression. Among 34 patients enrolled, ten of 28 SPTCL patients developed HLH/HLH-like systemic illnesses. Six cases with HAVCR2Y82C mutation manifested with HLH without panniculitis. Male sex (P=0.03) and age <18 years (P=0.04) were associated with HLH, corresponding to the inverse correlation between age and HLH-2004 score (r=-0.40; P=0.02). Homozygous HAVCR2Y82C mutation was more common in the presence of HLH compared with the absence (75.0% vs. 44.4%; P=0.02). Using IPD from the present and the other three eligible cohorts (N=127), male sex, heterozygous and homozygous/compound heterozygous HAVCR2 mutations were associated with HLH by the adjusted odds ratio of 2.93 (95% confidence interval [CI]: 1.22-7.06), 4.77 (95% CI: 1.05-21.63) and 8.48 (95% CI: 2.98-24.10), respectively. Patients with male sex and/or germline HAVCR2 mutations showed an increased risk of developing HLH. Younger patients tended to manifest with HLH, while older patients typically presented with SPTCL with less frequent HLH/HLH-like systemic illnesses

Isolated Thrombocytopenia in Thai Children: Etiology and Result of Bone Marrow Aspiration Study

Background: Isolated thrombocytopenia (IT) refers to an entity of low platelet count without abnormalities of other lineages. Previous studies revealed that the main cause of IT in children without atypical features i.e. hepa- tosplenomegaly or adenopathy was immune thrombocytopenia (ITP), while acute leukemia and aplastic anemia (AA) were other possible causes. However, there was no previous study in Thailand to identify the cause of IT. Objective: To study the bone marrow aspiration (BMA) result in Thai children with IT and to identify the cause of IT in Thai children. Methods: This was a retrospective chart review of children younger than 15 years old with IT who were diag- nosed at Siriraj Hospital during January 1996 to December 2010. All patients had BMA to identify the cause of thrombocytopenia. Demographic data, clinical manifestation, laboratory results including BMA finding, diagnosis and initial treatment were collected and analyzed. Results: One hundred and twenty-nine patients were enrolled to the study. All patients had normal or increased megakaryocytes in their bone marrow, and none of them had more than 5% of blast cells. Most patients (97.7%) were diagnosed as acute ITP while 2.3% were diagnosed with neonatal alloimmune thrombocytopenia. None of the patients had acute leukemia or AA. Conclusion: The BMA result of most patients in this study was compatible to that of ITP, that is none of the patients had acute leukemia or AA. The most common cause of IT in Thai children is acute ITP. This result sug- gested that BMA in children with IT before starting treatment is not necessary

Mediastinal Germinoma Associated with Hemophagocytic Lymphohistiocytosis: A Case Report

Background: Malignancy-associated hemophagocytic syndrome (MAHS), a secondary form of hemophagocytic lymphohistiocytosis (HLH), can be found with several types of malignancy. It can be manifested either before or after the diagnosis of the underlying malignancy. However, mediastinal germinoma associated HLH has never been reported in previous literatures. Case report: A 13-year-old boy presented with prolonged fever for 10 days with marked hepatosplenomegaly and progressive bicytopenia. Additional investigations demonstrated hyperferritinemia and increased hemophagocytic activity in the bone marrow without evidence of malignancy, compatible with the diagnosis of HLH. He responded well to the HLH-treatment with intravenous immunoglobulins and dexamethasone, but the HLH recrudesced 5 days later. Further investigation revealed anterior mediastinal mass. He quickly deteriorated afterwards and developed pulmonary hemorrhage leading to respiratory failure and died on the following day. Result of the post-mortem tumor biopsy was consistent with mediastinal germinoma. Conclusion: MAHS should be considered in HLH patients who do not respond well or develop recurrence after the appropriate HLH-immunochemotherapy. HLH associated with mediastinal germinoma is rare and fatal. Making diagnosis of the underlying mediastinal germinoma is complicated and challenging. Early diagnosis and prompt treatment of HLH along with the appropriate treatment of germinoma might be the important key for the treatment success