International consensus on mitotane treatment in pediatric patients with adrenal cortical tumors: indications, therapy, and management of adverse effects.

OBJECTIVE: Mitotane is an important cornerstone in the treatment of pediatric adrenal cortical tumors (pACC), but experience with the drug in the pediatric age group is still limited and current practice is not guided by robust evidence. Therefore, we have compiled international consensus statements from pACC experts on mitotane indications, therapy, and management of adverse effects. METHODS: A Delphi method with 3 rounds of questionnaires within the pACC expert consortium of the international network groups European Network for the Study of Adrenal Tumors pediatric working group (ENSAT-PACT) and International Consortium of pediatric adrenocortical tumors (ICPACT) was used to create 21 final consensus statements. RESULTS: We divided the statements into 4 groups: environment, indications, therapy, and adverse effects. We reached a clear consensus for mitotane treatment for advanced pACC with stages III and IV and with incomplete resection/tumor spillage. For stage II patients, mitotane is not generally indicated. The timing of initiating mitotane therapy depends on the clinical condition of the patient and the setting of the planned therapy. We recommend a starting dose of 50 mg/kg/d (1500 mg/m²/d) which can be increased up to 4000 mg/m2/d. Blood levels should range between 14 and 20 mg/L. Duration of mitotane treatment depends on the clinical risk profile and tolerability. Mitotane treatment causes adrenal insufficiency in virtually all patients requiring glucocorticoid replacement shortly after beginning. As the spectrum of adverse effects of mitotane is wide-ranging and can be life-threatening, frequent clinical and neurological examinations (every 2-4 weeks), along with evaluation and assessment of laboratory values, are required. CONCLUSIONS: The Delphi method enabled us to propose an expert consensus statement, which may guide clinicians, further adapted by local norms and the individual patient setting. In order to generate evidence, well-constructed studies should be the focus of future efforts.

Ganglioneuromas in Childhood: Hacettepe Experience With 70 Cases.

BACKGROUND: Ganglioneuromas (GNs) are rare benign peripheral neuroblastic tumors (PNTs). We shared our institutional experience with childhood GNs. METHODS: Records of the children with PNTs between January 1995 and December 2021 were reviewed, and cases with histopathological diagnoses of GN were identified. Clinical, laboratory, radiological, and histopathological findings, image-defined risk factors (IDRFs), procedures, and overall outcomes were recorded. RESULTS: Of 668 cases with PNTs, 70 (10.4%) had GNs. The median age was 7.4 years (range, 2.6-15.7 years) (girls/boys, 41/29). Common presenting complaints were abdominal pain and cough; 33/70 cases (47.1%) were diagnosed incidentally. Primary tumors were in the abdomen in 41/70, the thorax in 25/70, the neck in 3 cases, and the pelvis in one. The median tumor size was 6.5 cm (range, 1.4-17). Fifty cases (71.4%) were staged as INRG-L1; 20 cases with IDRFs (15 single, five >1) were staged as INRG-L2. Complete and partial tumor resections were performed in 58/70 and 6/70 cases, while 6 had no resection. The overall complication rate was 17.1% (11/64). At a median follow-up of 9 years, five were lost to follow-up; 65 were alive. One patient with gross residue underwent total resection due to progression 13 years after the surgery, and one in the unresected group was lost to follow-up. Ten other cases without a complete resection experienced no tumor progression. CONCLUSIONS: Ganglioneuromas are benign PNTs, and most are free of IDRFs. Even without complete resection, long-term outcomes are excellent. Guidelines should be devised considering the high surgical complication rates and benign course of GNs. LEVEL OF EVIDENCE: Case series, IV.

Primary ovarian tumors in children: a single center experience of 124 patients.

BACKGROUND: Primary ovarian tumors are rare in the pediatric age group. We reviewed our 40-year experience with ovarian tumors to evalute the clinical features and treatment results in a single institution. METHODS: Between January 1975 and October 2015, 124 girls with primary ovarian tumor were diagnosed and treated in our center. Tumors were identified with biopsy or total resection and/or serum markers. Seventy four children were included in the treatment analysis. RESULTS: Median age for 124 children was 11.0 years (0.73-17.63). The main complaint was abdominal pain in 85 patients (68.5%). One hundred and five patients (84.6%) had total one-sided salpingo-oophorectomy and five patients had bilateral salpingo-oophorectomy. Amongst 124 cases, 29 patients had mature teratoma, which was the most common tumor in this study. Dysgerminoma (n=21) was the most common malignant histopathologic type. Stage I disease was diagnosed in 57.2% and stage IV in 6.6% of the patients. Five year overall survival (OS) and event-free survival (EFS) for 124 children were 82.5% and 76.3% respectively. For 74 children who received treatment, 5-year OS and EFS were 75.2% and 67.1%, respectively. Age (p < 0.017), histopathological subgroup (p < 0.001), stage (p =0.003) and chemotherapy protocols (p =0.049) were significant prognostic factors for OS. CONCLUSIONS: The survival rates in children with ovarian tumors were comparable with studies in the literature. Although patients treated with platin based regimens had better survival rates, prognosis was still poor for the patients in advanced stages. This should be the focus for further studies and improvements.

Precursor B-cell Lymphoblastic Lymphoma in Children: Hacettepe Experience.

The purpose of the study was to review the clinical and pathologic characteristics and treatment results of children with precursor B-cell lymphoblastic lymphoma. Of 530 children diagnosed with non-Hodgkin lymphomas between 2000 and 2021, 39 (7.4%) were identified as having precursor B-cell lymphoblastic lymphoma. Clinical characteristics, pathologic, radiologic, laboratory data, treatments, responses, and overall outcomes were recorded from hospital files and analyzed. The median age of 39 patients (males/females, 23/16) was 8.3 years (range 1.3 to 16.1). The most common sites of involvement were the lymph nodes. At a median follow-up of 55.8 months, 14 patients (35%) had a recurrence of disease (11 stage IV, 3 stage III); 4 were in complete remission with salvage therapies, 9 died of progressive disease and one died due to febrile neutropenia. Five-year event-free survival and overall survival rates were 65.4% and 78.3% for all cases, respectively. Survival rates were higher in patients with a complete remission at the end of induction therapies. The survival rates were lower in our study compared with other studies, which could be explained by the high relapse rate and higher incidence of advanced-stage disease due to bone marrow involvement. We demonstrated a prognostic impact of treatment response at the end of the induction phase. Cases with a disease relapse have poor prognosis.

An unexpected intracardiac location of yolk sac tumor.

PURPOSE: In the pediatric population, intracardiac tumors are rare, usually benign, and mostly diagnosed as rhabdomyoma. Yolk sac tumors (YSTs) are a rare malignant type of germ celltumor that typically occurs in gonads. It can also be seen in midline locations but the intracardiac location is extremely rare. METHODS: The case herein comprises an asymptomatic 2.5-year-old girl with a murmur detected under general examination. RESULTS: Echocardiography showed a 3 × 3-cm mass in the right ventricle. Cardiac magnetic resonance imaging revealed a smooth contoured mass in the right ventricle lumen, which was compatible with rhabdomyoma. After surgical resection, the histopathological results showed a YST. This diagnosis was supported by high values of subsequent serum alpha feto-protein. There was no evidence for any other primary location. CONCLUSION: When an intracardiac mass is observed, a YST should be considered. The increase in the alpha feto-protein level can help in the differential diagnosis.

Clinical results of polidocanol sclerotherapy in venous malformation treatment: Patient-perceived improvement and satisfaction.

PURPOSE: This study evaluated the results of polidocanol sclerotherapy in the treatment of venous malformations (VM) including patient satisfaction, perceived improvement, and predictors of satisfaction. MATERIAL AND METHOD: Patients with VM that underwent polidocanol foam sclerotherapy between June 2013 and July 2021 in a single center were retrospectively evaluated. Patient demographics, VM, and treatment characteristics were analyzed. Patient-reported outcomes and satisfaction were analyzed with a questionnaire. RESULTS: This study included 232 (136, 58.6%, female) patients. The mean age was 24.49 ± 12.45 years (range 3-72). The clinical response rate was 82.3%. The rate of satisfaction was 82.3%, and 116 (50%) patients were significantly satisfied. There were no major complications. Clinical response and VM margin were related to satisfaction (p < 0.01, p = 0.012, respectively). Clinical response to pretreatment swelling was related to significant satisfaction (p = 0.02). CONCLUSION: Polidocanol sclerotherapy was safe and effective in VM treatment with high satisfaction and low complication rates.

Radiotherapy for pediatric adrenocortical carcinoma - Review of the literature.

Background and purpose: Pediatric adrenocortical carcinoma (pACC) is a rare disease with poor prognosis. Publications on radiotherapy (RT) are scarce. This review summarizes the current data on RT for pACC and possibly provides first evidence to justify its use in this setting. Materials and methods: We searched the PubMed and Embase database for manuscripts regarding RT for pACC. Results: We included 17 manuscripts reporting on 76 patients treated with RT, after screening 2961 references and 269 full articles. In addition, we added data of 4 unreported pACC patients treated by co-authors. All reports based on retrospective data. Median age at first diagnosis was 11.1 years (70% female); 78% of patients presented with hormonal activity. RT was mostly performed for curative intent (78%). 88% of RT were administered during primary therapy. The site of RT was predominantly the local tumor bed (76%). Doses of RT ranged from 15 to 62 Gy (median 50 Gy). Information on target volumes or fractionation were lacking. Median follow-up was 6,9 years and 64% of the patients died of disease, with 33% alive without disease. In 16 of 48 patients with available follow-up data after adjuvant RT (33%) no recurrence was reported and in 3 of 9 patients palliative RT seemed to induce some benefit for the patient. Conclusions: Our first systematic review on RT for pACC provides too few data for any general recommendation, but adjuvant RT in patients with high risk might be considered. International collaborative studies are urgently needed to establish better evidence on the role of RT in this rare malignancy.

Paediatric appendiceal neuroendocrine tumours: a review of 33 cases from a single center.

BACKGROUND: Appendiceal neurendocrine tumours (NETs) are rare neoplasms and diagnosis is commonly incidental following appendectomy. We aimed to review our experience with appendiceal NETs. METHODS: Records of children with appendiceal NETs were reviewed and data concerning demographic characteristics, clinical findings, surgical procedures, histopathological findings, management and outcomes were recorded. RESULTS: Between 1985 and 2021, 33 cases with appendiceal NETs (median age 11.8 years, range 7.8-16; male/female = 10/23) were identified. All but one patients presented with abdominal pain, six had vomiting, four had fever and they underwent appendectomies with presumed diagnosis of acute appendicitis. Abscess drainage and appendectomy was performed in a 16-year-old girl for suspected right ovarian mass, and tumour was positive in the omentum. Histopathological diagnosis was classical carcinoid tumour (NET) in all cases. Median tumour size was 0.9 cm (n = 26, range, 0.1-3.5 cm); tumours were ≤1 cm in 19 cases, 2 cm in one, 3.5 cm in another case. Tumours were located in the tip (n = 11), body (n = 6) and base of appendix (n = 1) (in others data unavailable). In 28 patients with data, tumour extended to submucosa in five, to tunica muscularis in seven, to subserosa in six, to serosa in six, to mesoappendix in three, to periappendiceal fat in one. Three cases were lost to follow-up, 31 cases were alive (median follow-up 53 months). CONCLUSIONS: Paediatric appendiceal NETs do not behave aggressively and appendectomy alone is sufficient for tumours ≤2 cm regardless of local invasion. The need for further extensive surgery in tumours >2 cm also remains controversial.

Nimotuzumab therapy in the treatment of pediatric central nervous system tumors: single-center experience.

Relapsed or refractory central nervous system (CNS) tumors still have poor prognosis, and, therefore, new treatment options are required. We retrospectively researched treatment results of patients with CNS tumors treated with nimotuzumab from 2010 to 2015. The study included nine patients with the diffuse intrinsic pontine glioma; eight with medulloblastoma; three each with anaplastic ependymoma, glioblastoma multiforme, and central nervous system primitive neuroectodermal tumor (CNS PNET); two patients with gliomatosis cerebri; and one patient each with other tumor types, including atypical teratoid rhabdoid tumor, thalamic astrocytoma, low-grade glial tumor, high-grade glial tumor, and cribriform neuroepithelial tumor. An objective response was observed in 10 of 33 patients with four patients showing a complete response, three a partial response, and three patients had stable disease. The 2-year overall survival (OS) and progression-free survival (PFS) rates were 35 ±9% and 19 ±8%, respectively. Due to the objective response in medulloblastoma, CNS PNET, and anaplastic ependymoma (MED group), survival rates of this group were analyzed. The 2-year OS and PFS for the MED group were 71 ±12% and 30 ±13%, respectively. The treatment was well tolerated. The treatment responses for medulloblastoma, CNS PNET, and anaplastic ependymoma have been promising. Likewise, some patients with relapsed or progressive CNS tumors may benefit through nimotuzumab-containing regimen.

Extraovarian juvenile granulosa cell tumor in a prepubertal child: novel location of a rare tumor.

Juvenile granulosa cell tumor (JGCT) is the most common type of sex cord stromal tumor arising from gonadal structures of children and young adults. We present a 3.5-year-old girl with JGCT located in retroperitoneum without ovarian involvement. Extragonadal occurrences of other sex cord stromal tumors have been rarely reported, but this is the first case of JGCT in an extragonadal location. We speculate the possible underlying mechanism of sex cord stromal tumor formation in extragonadal locations. Furthermore, clinical presentation, differential diagnosis and management of this tumor in childhood are discussed.

Hemangioma fusocelular en las fosas nasales y los senos etmoidales en un lactante de 4 meses de edad / Spindle cell hemangioma of nasal passage and ethmoidal sinus in a 4-month old infant

El hemangioma fusocelular es una neoplasia vascular benigna infrecuente. Afecta la dermis y la hipodermis de la parte distal de las extremidades; la afectación de la cabeza y el cuello es muy poco frecuente y nunca se informó compromiso de los senos paranasales. Este es el caso de un lactante de 4 meses con obstrucción nasal desde las 2 semanas debido a un tumor en los senos etmoidales que obstruía las fosas nasales. Se diagnosticó hemangioma fusocelular y se extirpó parcialmente el tumor. A los seis meses de seguimiento, se observó una regresión mínima con lesiones residuales. A los 30 meses, se observó que el tumor residual había desaparecido. El hemangioma fusocelular es infrecuente en cabeza y cuello y, a veces, la presentación no es indicativa del diagnóstico. El examen histopatológico ayuda con el diagnóstico diferencial y el tratamiento. La sensibilización sobre el hemangioma fusocelular podría aumentar los casos informados.

Spindle cell hemangioma (SCH) is a benign unusual vascular neoplasm. It does not have gender predilection and can occur at all ages. The disease affects dermis and subcutis of distal extremities predominantly; head and neck involvement is very rare, paranasal sinus involvement has not been reported before. Herein we present a 4-month-old infant with nasal obstruction since two weeks of age due to a mass in ethmoid sinus obliterating the nasal passage. After the histopathological diagnosis of SCH, the tumor was partially resected. In the sixth month follow-up, there was minimal regression of residual lesions. In the imaging studies performed 30 months after the surgery, the residual mass was found to be disappeared. SCH is not frequent in the head and neck, and presentation of some patients may not suggest the diagnosis. Histopathology is important for differential diagnosis and to orientate treatment. Awareness of SCH may increase the reported cases

Spindle cell hemangioma of nasal passage and ethmoidal sinus in a 4-month old infant. / Hemangioma fusocelular en las fosas nasales y los senos etmoidales en un lactante de 4 meses de edad.

Spindle cell hemangioma (SCH) is a benign unusual vascular neoplasm. It does not have gender predilection and can occur at all ages. The disease affects dermis and subcutis of distal extremities predominantly; head and neck involvement is very rare, paranasal sinus involvement has not been reported before. Herein we present a 4-month-old infant with nasal obstruction since two weeks of age due to a mass in ethmoid sinus obliterating the nasal passage. After the histopathological diagnosis of SCH, the tumor was partially resected. In the sixth month follow-up, there was minimal regression of residual lesions. In the imaging studies performed 30 months after the surgery, the residual mass was found to be disappeared. SCH is not frequent in the head and neck, and presentation of some patients may not suggest the diagnosis. Histopathology is important for differential diagnosis and to orientate treatment. Awareness of SCH may increase the reported cases.

El hemangioma fusocelular es una neoplasia vascular benigna infrecuente. Afecta la dermis y la hipodermis de la parte distal de las extremidades; la afectación de la cabeza y el cuello es muy poco frecuente y nunca se informó compromiso de los senos paranasales. Este es el caso de un lactante de 4 meses con obstrucción nasal desde las 2 semanas debido a un tumor en los senos etmoidales que obstruía las fosas nasales. Se diagnosticó hemangioma fusocelular y se extirpó parcialmente el tumor. A los seis meses de seguimiento, se observó una regresión mínima con lesiones residuales. A los 30 meses, se observó que el tumor residual había desaparecido. El hemangioma fusocelular es infrecuente en cabeza y cuello y, a veces, la presentación no es indicativa del diagnóstico. El examen histopatológico ayuda con el diagnóstico diferencial y el tratamiento. La sensibilización sobre el hemangioma fusocelular podría aumentar los casos informados.

Adrenocortical tumours in children: a review of surgical management at a tertiary care centre.

BACKGROUND: Adrenocortical tumours (ACT) are rare tumours of childhood usually presenting with endocrine dysfunction. This retrospective study is designed to review our institutional experience in surgical management. METHODS: Records of children treated for ACT between 1999 and 2019 were reviewed retrospectively. RESULTS: The median age of 24 children was 78 months. Fourteen patients had adrenocortical carcinoma, nine had adrenocortical adenoma and one had neuroendocrine differentiation of ACT. Endocrine dysfunction was noted in 79% of the patients. Five patients had preoperative chemotherapy but none had a decrease in tumour size. Transabdominal approach was used in all but two patients who had thoracoabdominal incision for excision of giant tumours and ipsilateral lung metastases. Two patients had visceral excision to achieve R0 resection. Five patients, four of whom had spillage and one with partial resection died of widespread disease. Two patients with stage 4 adrenocortical carcinoma are still on chemotherapy. All patients with stage I-III disease who had total excision without spillage (n = 17) are disease-free for 2-170 months. CONCLUSIONS: Our results show the importance of excision in ACT without spillage for survival. However, multicentre prospective studies should enhance the knowledge of children about ACT and develop alternative therapies for stage III and IV cases.

Primary spinal multifocal intradural-extramedullary Ewing sarcoma in children: presentation of a case and review of the literature.

BACKGROUND: Primary spinal, intradural, extramedullary Ewing sarcoma (PSIEES) is exceptionally uncommon. Here, we present an interesting pediatric case with a PSIEES diagnosis confirmed by the presence of a specific fusion protein in the tumor tissue and who then developed a cerebellar recurrence. We also reviewed the PSIEES cases in childhood reported in the literature. CASE: An 8.5-year-old boy was admitted to a local hospital with a one-month history of severe back and limb pain, and inability to move his lower limbs. Physical examination revealed paraparesis in the lower extremities. Spinal MRI revealed multiple intradural extramedullary masses at the L2-L3, L4-5 and L5-S1 levels. He underwent surgery and near total excision of all three masses were performed. Histopathological diagnosis of Ewing Sarcoma was confirmed with EWS-ERG gene rearrangement. The patient was treated according to EuroEwing chemotherapy protocol. A total dose of 4500 cGy radiotherapy was applied to the tumor location at L2-S1 paravertebral region. Eighteen months after the end of treatment, a mass in the left cerebellar hemisphere was determined. Gross total excision was performed. Histopathological examination of the tumor showed Ewing sarcoma. Radiological screening revealed isolated central nervous system recurrence. A total of 4500 cGy radiotherapy was applied. He is on a second-line treatment consisting of gemcitabine and docetaxel without any evidence of disease. CONCLUSIONS: Ewing Sarcoma with spinal intradural region in childhood is very rare. We could only find 17 pediatric cases reported in the literature. Neurological findings occur earlier in tumors of this region. The prognosis is worse than other extraosseous Ewing sarcoma.

Assessment of nutritional status in children with cancer: Significance of arm anthropometry and serum visceral proteins.

BACKGROUND: Arm anthropometry is a better indicator of nutritional status in children with cancer. The value of serum albumin and prealbumin in nutritional assesment is debatable. We investigated the nutritional status of children with cancer and their serum albumin and prealbumin levels. PATIENTS AND METHODS: At diagnosis and following induction therapies, weight, height, body mass index (BMI), mid-upper arm circumference (MUAC), and triceps skin-fold thickness (TSFT) were measured; serum albumin and prealbumin levels were determined. Prevalences of malnutrition defined by anthropometric indices were calculated. Correlations of anthropometric indices with each other, with serum albumin/prealbumin levels, and clinicopathological parameters were analyzed. RESULTS: In 81 patients, median age was 7.5 years (males/females = 50/31), tumors were located mostly in the abdomen, and abdominal tumors were more common under 5 years. Prevalence of malnutrition according to weight for age, BMI, MUAC, TSFT z scores were 14.8%, 23.5%, 27.2%, 21%, respectively. Defined by combined BMI/MUAC/TSFT measurements, 33/81 cases (40.7%) had malnutrition (z scores < -1, 23 mild; z scores < -2, 10 moderate). Malnutrition was more prevalent under 5 years (P = .03), also in abdominal tumors (P = .03) and advanced disease (P < .001). Younger age and advanced disease were risk factors for malnutrition. At diagnosis, prevalences of low serum albumin and prealbumin levels were 7.4% and 54%, respectively. Cases with malnutrition had significantly lower survival rates. CONCLUSIONS: Nutritional status is assessed best by MUAC and TSFT measurements. Serum prealbumin levels can be used to identify patients at risk of undernutrition. Presence of malnutrition is a significant poor prognostic factor. All children with cancer should undergo nutritional evaluation and active nutritional support.

Primary Paraspinal and Spinal Epidural Non-Hodgkin Lymphoma in Childhood.

Primary paraspinal/spinal epidural lymphoma (PPSEL) is rare in childhood. Here, we retrospectively evaluated patients with PPSEL treated in our department. We also reviewed the cases reported in the literature. Fifteen of 1354 non-Hodgkin lymphoma cases diagnosed over a 38-year period were PPSEPL. There were 11 male individuals and 4 female individuals with a median age of 13 years. Most common symptoms were pain and limb weakness. Physical examination revealed spinal cord compression in 80% of patients. The most common tumor location was the lumbar region. Histopathologic subtypes were lymphoblastic lymphoma in 6 and Burkitt lymphom in 5 patients. Subtotal or near-total excision of the tumor with laminectomy was performed in 6 patients. Thirteen and 9 patients received chemotherapy and radiotherapy, respectively. Neurologic recovery was observed in 70% of patients. Seven patients were alive without disease at a median of 88 months. Overall and event-free survival rates were 61.7% and 50.1%, respectively. We reviewed clinical features, treatment, and outcome of 69 PPSEL cases reported in the literature. Neurologic recovery and long-term survival was achieved in 66.7% of them. Heterogeneity in diagnostic methods and treatment have made it difficult to establish the prognostic indicators for neurologic outcome and survival. Multicenter prospective studies with more cases are necessary to determine the prognostic factors.

Serum levels of VEGF and bFGF in infantile hemangiomas treated with propranolol.

BACKGROUND: Infantile hemangiomas (IH) represent the most common type of benign tumors of infancy. Vascular endothelial growth factor (VEGF) and basic fibroblastic growth factor (bFGF) have a central role in the pathogenesis of infantile hemangiomas. METHODS: In this prospective study, we aimed to investigate the relationship between serum VEGF and bFGF levels and clinical characteristics and the serological changes in VEGF and bFGF levels associated with propranolol treatment in infants diagnosed with IH. Blood samples were taken from 34 patients with IH and 10 controls. Serum VEGF and bFGF levels were studied by ELISA. RESULTS: At initial diagnosis, median serum bFGF levels were 11.1 ng/ml (4.8-16.6) in patients with IH (n=34) and 2.6 ng/ml (1.7-4.7) in controls (p < 0.001), and, median serum VEGF levels for same groups were 58.5 ng/ml (25.3-190.2) and 11.4 ng/ml (8.2-19.8) (p < 0.001), respectively. Serum VEGF and bFGF levels were not correlated. In 18 infants who were treated with propranolol with serial measurements, median serum bFGF levels were 10.7 ng/ml, 9.8 ng/ml and 10.5 ng/ml (p= 0.8), and median serum VEGF levels were 68.6 ng/ml, 63.5 ng/ml and 45.1 ng/ml (p < 0.001) at initial diagnosis, at first and third months, respectively. Median regression rates of the hemangiomas at the first and third months were -%47.3 and -%58.3 (p < 0.001), respectively. CONCLUSIONS: Serum bFGF levels didn`t change in time. Serum VEGF levels seemed to follow the natural course of IH and might be a marker for follow-up. The contribution of propranolol treatment should also be considered.

Primary intracranial germ cell tumors in children 36-year experience of a single center.

PURPOSE: Intracranial germ cell tumors (ICGCTs) comprise approximately 0.4%-3% of all brain tumors. In this study, we aim to evaluate clinical characteristics, treatment and outcomes of patients with ICGCT. PATIENTS AND METHODS: All patients with ICGCT diagnosed in Hacettepe University's Pediatric Oncology Department between January 1980 and January 2016 were evaluated, retrospectively. RESULTS: We identified 52 patients (male/female: 2.46) diagnosed with ICGT. Median age was 140 months. The median duration of symptoms was 3 months. Patients with endocrine symptoms were diagnosed later than others (P = 0.028). The primary site was pineal region in 20 patients, nonpineal region in 32 which included six bifocal involvements. Pineal location was more common in boys than girls (P = 0.02). Histopathological diagnosis was germinoma in 28 patients, nongerminomatous malignant germ cell tumors in 14 and immature teratoma in 4. The mean age for germinoma was higher than that of nongerminomatous tumors (P = 0.032). Patients treated with surgery and radiotherapy and chemotherapy. Median follow-up time was 52.5 months. Thirty-six patients were alive for 12-228 months. Relapsed/progressive disease was observed in 11 patients. Nongerminomatous tumors more frequently showed relapse/progression than germinoma (P = 0.06). Five-year overall and event-free survival rates for the whole group were 72.6% and 57.2%, respectively. Overall and event-free survival rates for germinoma were better than malignant nongerminomatous tumors. CONCLUSION: Although the ratio of ICGCTs to central nervous system tumors in our series was similar to western countries, some clinical features such as tumor location were similar to cases from East Asian countries. Although similar protocols were used survival rates lower than developed western and eastern developed countries.

Circulating Epstein-Barr virus DNA and cell-free DNA in pediatric lymphomas.

BACKGROUND AND OBJECTIVES: Quantification of serum Epstein-Barr virus (EBV) DNA and/or cell-free total DNA (cf-DNA) may become valuable sources for prognosis evaluation and monitoring treatment response in lymphomas. We aimed to investigate their roles as potential markers in pediatric Hodgkin (HL) and non- Hodgkin lymphomas (NHL). METHOD: Between the years 2005-2008, 34 patients with HL and 45 with NHL were prospectively included. Serum samples were collected upon diagnosis, after 1-3 and 4-6 months and at the end of treatment, or at disease recurrence. RT-PCR determination of cf-DNA and EBV DNA were performed using amplification of BAMH1W region of EBV genome and of human ß-globin gene. Results were analyzed for correlation with clinical and pathological characteristics. RESULTS: Median ages were 8.9 years for HL and 8.8 years for NHL cases. Twenty-three healthy children cured from various childhood cancers served as the control group. In the controls, median serum EBV DNA copy number was `0` and median serum cf-DNA level was 50 ng/ml. At initial diagnosis, serum EBV DNA copy numbers were elevated in 20/34 HL and 8/45 NHL cases (p < 0.001). Median serum EBV DNA copy numbers were 15987/mL (125-6032075) and 25162 (1475-1214550) for HL and NHL cases, respectively (p= 0.9). Median serum cf-DNA levels were 435 ng/ml (2.3-17306) in HL and 700 ng/ml (4.9-14009) in NHLs (p= 0.12). Serum EBV DNA copy numbers and cf-DNA levels decreased significantly after induction treatment and in the follow-up. In 10/13 NHL cases with a relapse, marked elevations were detected in serum cf-DNA levels at recurrences. No significant differences were detected between median cf-DNA levels according to disease stages, response status to treatment or presence of recurrent disease. CONCLUSION: Serum EBV DNA copy numbers and cf-DNA levels were elevated at initial diagnosis in both HLs and NHLs and decreased parallel to treatment response. In NHL cases, remarkable elevation of cf-DNA levels at recurrences indicated that cf-DNA levels might be useful in the follow-up of pediatric NHLs.

Primary gastric lymphoma: A report of 16 pediatric cases treated at a single institute and review of the literature.

Gastrointestinal tract is the most common extranodal site for childhood non-Hodgkin lymphomas (NHLs). However, primary gastric lymphoma (PGL) is very rare. We report our experience with PGL. Between 1972 and 2019, patients with PGL among 1696 NHL cases were evaluated retrospectively. Patient characteristics, treatments, and survival rates were recorded. We also reviewed the cases reported in literature. There were 16 PGL (11 males, five females) cases with a median age of 10 years. Most frequent complaints, similarly to the literature, were pain and vomiting. Hematemesis/melena and anemia were present in 20% of patients. Most common tumor location was antrum. Histopathological subtypes were Burkitt and non-Burkitt B-cell lymphoma in 43.75% and marginal zone lymphoma (MZL) in 6.25% of cases while mucosa-associated lymphoid tissue (MALT) and low-grade lymphomas constitute 15.3% of cases reported in the literature. In our series, Helicobacter pylori (H. pylori) was analyzed in only the case with MZL and found to be positive. However, H. pylori positivity was reported in 75% of the cases in the literature. H. pylori eradication, chemotherapy, and radiotherapy were applied in one, 14, and five patients. Subtotal gastrectomy with gastroduodenostomy/jejunostomy was performed in three patients. Gastrojejunostomy was done without tumor resection in two patients. Nine patients lived without disease for a median of 59 (12-252) months. Five-year EFS and OS were 69.6% and 64.3%, respectively. PGL constitutes 0.94% of our NHL cases. Interestingly, most of the cases in the literature were from Turkey. While adult PGL is mostly MALT lymphoma, most pediatric cases had high-grade histopathology. Although surgery and radiotherapy were applied earlier, chemotherapy alone is sufficient.