Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs.

Atypical teratoid rhabdoid tumor in childhood, 15 cases of a single institute experience.

OBJECTIVE: Atypical teratoid rhabdoid tumor is a rare neoplasm with a distinct cytogenetic profile that predominates in infancy. Many cases show predominance of small cells with scanty rhabdoid cells, making recognition of this tumor difficult. We aim at describing our experience with atypical teratoid rhabdoid tumor cases diagnosed over a 6-year period. MATERIAL AND METHOD: Clinicopathologic features and immunohistochemical staining of atypical teratoid rhabdoid tumor cases diagnosed between 2006 and 2011 are presented. RESULTS: Fifteen cases were identified including 9 males with a median age of 26 months. The most common presenting symptom was recurrent vomiting with a mean duration of 6 weeks. Nine cases (60%) were infratentorial and cerebrospinal fluid was positive in 2 cases (13.3%) at time of diagnosis. The median overall survival of the group was 9.5 months. All cases except one showed admixture of rhabdoid and/or small round blue cells in variable proportions. Only 5 out of fourteen referred cases (35.7%) were correctly diagnosed. Three cases showed unusual growth patterns. In 2 cases, nodular medulloblastoma-like growth pattern predominated, with loss of INI-1/BAF47 staining both within the nodules and the inter-nodular areas. The third case contained scattered individual and small groups of large cells with abundant acidophilic cytoplasm and eccentric nuclei, reminiscent of rhabdomyoblasts that were positive for GFAP and desmin, and retained nuclear staining for INI-1/BAF47, consistent with reactive gemistocytes. CONCLUSION: Pathologists should be aware of the various, and unusual histopathologic patterns of atypical teratoid rhabdoid tumor. INI-1/ BAF47 immunostain should be performed on all central nervous system embryonal tumors, especially in infants and young children.

Central nervous system tumors in the first year of life: a clinical and pathologic experience from a single cancer center.

PURPOSE: This study aims to review our experience with central nervous system (CNS) tumors occurring during the first year of life and to report differing features found in our series. METHODS: This is a retrospective study of infants with CNS tumors diagnosed at our institution from 2006 to 2011. RESULTS: A total of 19 cases were identified, with a median age of 232 days and predominance of male gender. Males were younger than females at the time of diagnosis (p value = 0.039). There were 13 low-grade tumors, glial tumors being the most common (11/13, p value = 0.003) and six high-grade tumors, atypical teratoid rhabdoid tumor being the most common (4/6). Low-grade tumors predominated in the supratentorial region, while high-grade tumors were seen in the infratentorial area (p value = 0.035). Males had a predilection to have more supratentorial tumors (p value = 0.058). Four patients underwent gross total resection, and eight received chemotherapy; none received radiotherapy. Two patients had spinal cord tumors; both were of pilomyxoid astrocytoma histology. Rare tumors included hemangiopericytoma (n = 1) and atypical choroid plexus tumor (n = 1), both occurring in the supratentorial area and affecting the youngest patients in this group; they were diagnosed prenatally and at 107 days, respectively. The median progression-free and overall survivals were 269 and 667 days, respectively. Among all tested parameters, only the grade of the tumor affected the outcome. CONCLUSIONS: Diagnosis and management of infant's CNS tumors remain challenging. Pathologists should be aware of the diversity of histological types. Assigning appropriate tumor grade is fundamental in predicting the outcome.

Improved care of rhabdomyosarcoma in Jordan using less intensive therapy.

BACKGROUND: The care of rhabdomyosarcoma (RMS) is complex due to its multimodal nature. By following standard protocols with acceptable toxicity and building local expertise, better outcome should be achievable. PROCEDURE: A retrospective study was conducted of records of patients (n = 45; 31 males; median age 26 months) with RMS treated at King Hussein Cancer Center in Jordan from January 2004 to December 2008. Patient demographics, tumor characteristics, risk stratification, treatment plan, and outcomes were studied. In June 2006, the cyclophosphamide dose was lowered from 2.2 g/m(2) to 1.2 g/m(2) per cycle because of the significant toxicity with higher dose. Survival rates, hematological toxicities, period of hospitalization due to febrile neutropenia (FN), and response rate at week 12 of treatment were compared between low- and high-dose cyclophosphamide groups. RESULTS: Four-year progression-free survival (PFS) and overall survival (OS) rates were 61% ± 7.5% and 72% ± 6.9%, respectively. There was a significant difference in outcome by risk group in 4-year PFS (low-risk, 88% ± 12%; intermediate-risk 63% ± 9.3%; high-risk, 14% ± 13%; P = 0.0001) and OS (low-risk, 88% ± 12%; intermediate-risk 79% ± 7.5%; high-risk, 17% ± 15%; P = 0.0011). There was significant reduction in hematological toxicities, incidence of FN, and period of hospitalization for FN in patients given low-dose cyclophosphamide but no significant difference in PFS between low- and high-dose cyclophosphamide groups. CONCLUSIONS: Survival rates of patients with RMS in some developing countries can be improved by following or modifying evidence-based approaches successful in developed countries and establishing multidisciplinary strategies. Therapy intensity should be increased in developing countries only when evidence supports its utility.

Brain stem gliomas: a clinicopathological study from a single cancer center.

Brain stem gliomas (BSG) are rare tumors occurring predominantly in childhood. They are mostly of astrocytic origin and are divided into infiltrative versus circumscribed types, with different prognoses. The diagnosis is mainly based on MRI findings, and biopsy is rarely performed. This is a retrospective study of BSG with available biopsies diagnosed at our center over 6-year period. Fifteen cases were identified, with a predominance of females. The median age was 7 years, and the mean duration of symptoms was <6 weeks in 58.3% (n = 7) of cases. MRI was typical of diffuse pontine gliomas in 64.3% (n = 9) of cases. Radiotherapy was the commonest modality of treatment, and the median overall survival was 21.7 months. Twelve cases were consistent with infiltrative astrocytoma of various grades (2 grade II, 7 grade III and 3 grade IV). Entrapped normal neurons and mitosis were the commonest findings indicating infiltrative growth and high grade, respectively, and those correlated significantly with immunostaining for neurofilament protein and Ki-67 of ≥3%. Overall survival correlated only with the duration of symptoms and tumor grade on biopsies. A limited panel of immunostains might be useful in undetermined cases to decide on the growth pattern and grade.

Ovarian germ cell tumors with rhabdomyosarcomatous components and later development of growing teratoma syndrome: a case report.

INTRODUCTION: Development of a sarcomatous component in a germ cell tumor is an uncommon phenomenon. Most cases reported have a grim prognosis. Growing teratoma syndrome is also an uncommon phenomenon and occurs in approximately 2% to 7% of non seminomatous germ cell tumors and should be treated surgically. CASE PRESENTATION: We report the case of a 12-year-old Asian girl with an ovarian mixed germ cell tumor containing a rhabdomyosarcomatous component. She was treated with a germ cell tumor chemotherapy regimen and rhabdomyosarcoma-specific chemotherapy. Towards the end of her treatment, she developed a retroperitoneal mass that was increasing in size. It was completely resected, revealing a mature teratoma, consistent with growing teratoma syndrome. She is still in complete remission approximately three years after presentation. CONCLUSION: The presence of rhabdomyosarcoma in a germ cell tumor should be treated by a combined chemotherapy regimen (for germ cell tumor and rhabdomyosarcoma). In addition, development of a mass during or after therapy with normal serum markers should raise the possibility of growing teratoma syndrome that should be treated surgically.

Embryonal tumor with abundant neuropil and true rosettes: a report of three cases of a rare tumor, with an unusual case showing rhabdomyoblastic and melanocytic differentiation.

Embryonal tumor with abundant neuropil and true rosettes (ETANTR) is an increasingly recognized entity that belongs to the family of embryonal tumors of the CNS. The authors present three cases of this rare tumor that were encountered at King Hussein Cancer Center, Amman, Jordan. Discussion of the clinicopathological findings is presented along with a recent literature review. Sixteen-, 57- and 30-month-old children presented with tumors located in the pineal gland, the right fronto- parieto-temporal region and the cerebellum, respectively. The findings of hypocellular neuropil as well as the characteristic ependymoblastic rosettes were seen. In addition the third case showed an abnormal combination of patterns including melanocytic and rhabdomyoblastic differentiation. The tumors stained positively for synaptophysin in the neuropil and small cell component, while the ependymoblastic rosettes stained for vimentin only. Epithelial membrane antigen and CD99 were negative in all components. One of the cases showed tetraploidy of chromosome 2. All cases exhibited an aggressive course. This is a rare and recently recognized tumor with dismal outcome, and reporting of additional new cases should help in gaining more knowledge about it.

Precocious puberty in an infant with hepatoblastoma: a case report.

INTRODUCTION: The syndrome of isosexual precocious puberty associated with primary malignant hepatic tumors is rare. All previously reported cases in the literature are old and prognosis was grim. CASE PRESENTATION: We present the case of a 15-month-old Asian male baby who presented with precocious puberty associated with hepatoblastoma. Serum concentrations of alpha-fetoprotein and free testosterone were elevated, as was beta human chorionic gonadotropin hormone. He was treated with six courses of chemotherapy and underwent surgery. His surface markers as well as free testosterone level returned to normal during therapy. The child has now been off therapy for 18 months with no evidence of tumor recurrence at follow-up. CONCLUSION: Virilizing hepatoblastoma is rare and reported with poor outcome, but the development of new chemotherapeutic agents and complete surgical resection are promising.

Distinct features of teratoid Wilms tumor.

Teratoid Wilms tumor is an unusual variant of nephroblastoma in which heterologous tissue predominates. Typically, histopathologic examination shows a mixture of mature squamous and mucus-producing columnar epithelium and a prominent component of mature adipose tissue. The treatment of this tumor has not been established because of its rarity with some reports doubting the value of chemotherapy. We report 3 new cases and review the 23 previously reported cases that we were able to identify. The first case was a 2-year-old boy with a huge tumor that occupied most of the abdominal cavity. The second case was a 5-year-old girl with a metastatic tumor in association with horseshoe kidney and is the first case of teratoid Wilms tumor with brain metastasis. The third case was an 11-month-old girl with bilateral involvement. Imaging studies of our patients were similar to those reported in the literature with areas of fat attenuation and calcification. Failure to respond to preoperative chemotherapy was seen in our patients and in most previously reported cases that were treated with preoperative chemotherapy. We recommend treating this entity with protocols designed for Wilms tumor and to conduct further basic research to understand its biologic nature.

Soft tissue sarcomas in the first year of life.

BACKGROUND: Soft tissue sarcomas (STS) occurring in the first year of life represent a rare entity. Challenges in delivering optimal therapy may affect the outcome in this very young population. METHODS: We searched the SEER database for records of infants less than 1 year of age, with a reported diagnosis of STS who were diagnosed from 1973 to 2006. We analysed their clinical features and survival. These patients were also compared to older patients (1-18 years old) in order to understand the differences between the two groups. RESULTS: The incidence rate of STS in the first year of life was 16.0 per million. As an entity, they represented 7.3% of malignancies reported in the first year of life. One fifth of these tumours (20.9%) were reported to be metastatic at diagnosis. The most common histologies were rhabdomyosarcoma (n=99, 32.8%), fibrosarcoma (n=74, 24.5%), malignant rhabdoid tumours (n=43, 14.2%) and haemangiopericytoma (n=12, 4.0%); except for rhabdomyosarcoma, the other 3 entities were very rare in older children. The 5-year survival of STS in children less than 1 year of age (62+/-3.0%) was significantly worse than that of older children (71+/-0.9%, P=0.0002). In a multivariate model, histologic types other than fibrosarcoma and haemangiopericytoma (HR, 5.7; 95% CI, 2.28-14.20) as well as advanced stage (HR, 5.15; 95% CI, 3.28-8.10) were found to be significant adverse prognostic factors. Significantly less use of radiation was reported in infants when compared to older children (P<0.0001). CONCLUSION: As a group, infantile STS are associated with worse survival than STS in older children. Outcome, however, is significantly associated with histologic subtype, with infantile fibrosarcoma and infantile haemangiopericytoma having better outcomes. Avoidance of radiotherapy in this young age may contribute to worse outcomes.

Local control of the primary tumour in metastatic neuroblastoma.

The previous studies have stressed on the importance of loco-regional control in the management of high-risk neuroblastoma. We searched the Surveillance, Epidemiology and End-Results (SEER) database for patients older than 2years with metastatic neuroblastoma who were diagnosed from 1998 to 2005. We identified 291 patients (mean age, 4.35years). The 5-year survival estimate was 53.2%+/-6.4% for patients who had complete resection of their primary tumours (n=116) and 35.7%+/-4.7% for patients who did not have complete resection (p=0.003). External-beam radiotherapy did not affect survival (p=0.79); this finding has to be taken with caution due to the study limitations.