Medulloepithelioma with heterologous osteoid component: a case report and review of literature.

PURPOSE: Medulloepithelioma is a rare brain tumor that has been classified as embryonal tumor with multilayered rosettes (ETMR) if it harbors C19MC amplification. In rare instances, it shows evidence of heterologous differentiation. METHODS: We report a case of a 10-year-old female who presented with headache, squint, and minimal left sided weakness of 1 week duration. RESULTS: Microscopy revealed a small round blue cell tumor with focal glandular and tubular differentiation. In one focus, well-developed osteoid was identified. The tumor labeled with LIN28A immunostain. CONCLUSIONS: Unusual features can be encountered in medulloepithelioma which should be in the differential diagnosis of CNS embryonal tumors. Full description of the case with review of the literature and comparison between cases with and without heterologous elements is presented.

Sustained Response to Targeted Therapy in a Patient With Disseminated Anaplastic Pleomorphic Xanthoastrocytoma.

Pleomorphic xanthoastrocytoma is a rare brain tumor with unique high frequency of BRAF V600E mutation which is plausible for targeted therapy. The anaplastic variant has generally worse prognosis. We present an adolescent patient with a disseminated relapse of anaplastic pleomorphic xanthoastrocytoma following surgery, radiotherapy, and chemotherapy. She had a dramatic and prolonged response to a BRAF inhibitor (Dabrafinib) and later to addition of a MEK inhibitor (Trametinib) on tumor progression. With minimal side effects and a good quality of life, the patient is alive more than 2 years after initiation of targeted therapy. This experience confirms the potential role of targeted treatments in high-grade BRAF-mutated brain tumors.

Review of management and morbidity of pediatric craniopharyngioma patients in a low-middle-income country: a 12-year experience.

BACKGROUND: Management of craniopharyngioma in children is challenging, and their quality of life can be significantly affected. Series describing this from low-middle income countries (LMIC) are few. PATIENTS AND METHODS: The study provides a retrospective chart review of pediatric patients <18 years old, diagnosed with craniopharyngioma between 2003 and 2014, and treated at King Hussein Cancer Center, Jordan. RESULTS: Twenty-four patients (12 males) were identified. Median age at diagnosis was 7.4 years (0.9-16.4 years). Commonest symptoms were visual impairment and headache (71%). Review of seventeen preoperative MRIs showed hypothalamic involvement in 88% and hydrocephalus in 76%. Thirteen patients (54%) had multiple surgical interventions. Five patients (21%) had initial gross total resection. Eleven patients (46%) received radiotherapy and six (25%) intra-cystic interferon. Five years' survival was 87 ± 7% with a median follow-up of 4.5 years (0.3-12.3 years). Four patients (17%) died; one after post-operative cerebral infarction and three secondary to hypothalamic damage. At their last evaluation, all but one patient required multiple hormonal supplements. Ten patients (42%) had best eye visual acuity (VA) >20/40, and four (16%) were legally blind. Eleven patients (46%) were overweight/obese; one had gastric bypass surgery. Seven patients had hyperlipidemia, and eight developed fatty liver infiltration. Eleven patients (65%) were attending schools and one at college. Nine of the living patients (53%) expressed difficulty to engage in the community. CONCLUSIONS: Management of pediatric craniopharyngioma is particularly complex and demanding in LMIC. Multidisciplinary care is integral to optimize the care and minimize the morbidities. A management outline for LMIC is proposed.

High frequency of mismatch repair deficiency among pediatric high grade gliomas in Jordan.

Biallelic mismatch repair deficiency (bMMRD) is a cancer predisposition syndrome affecting primarily individuals from consanguinous families resulting in multiple childhood cancers including high grade gliomas (HGG). This is the first study to assess the prevalence of bMMRD among patients with HGG in countries where consanguinity is high. We collected molecular and clinical information on all children diagnosed with HGG and supratentorial primitive neuroectodermal tumors (sPNET) between 2003 and 2013 at King Hussein Cancer Center, Jordan. Comparison was made to a similar cohort from Toronto. Clinical data regarding presence of café au lait macules(CAL), family history of cancer, consanguinity, pathology and treatment were collected. Tumors were centrally reviewed and tested for MMRD by immunohistochemistry of the corresponding proteins. Forty-two patients fulfilled the inclusion criteria, including 36 with HGG. MMRD was observed in 39% of HGG of whom 79% also lost MMR staining in the corresponding normal cells suggestive of bMMRD. P53 dysfunction was highly enriched in MMR deficient tumors (p = 0.0003).The frequency of MMRD was significantly lower in Toronto cohort (23%, p = 0.03). Both evidence of CAL and consanguinity correlated with bMMRD (p = 0.005 and 0.05,respectively) but family history of cancer didn't. HGG with all three bMMRD risk factors had evidence of MMRD and all children affected by multiple bMMRD related cancers had identical gene loss by immunohistochemical staining. In Jordan, the frequency of clinical and immunohistochemical alterations suggestive of bMMRD in pediatric HGG is high. Genetic testing will enable appropriate counseling and cancer screening to improve survival of these patients.

Synchronous glioblastoma and medulloblastoma in a child with mismatch repair mutation.

Synchronous primary malignant brain tumors are rare. We present a 5-year-old boy with synchronous glioblastoma and medulloblastoma. Both tumor samples had positive p53 stain and loss of PMS2 and MLH1 stains. The child had multiple café au lait spots and a significant family history of cancer. After subtotal resection of both tumors, he received craniospinal radiation with concomitant temozolomide followed by chemotherapy, alternating cycles of cisplatin/lomustine/vincristine with temozolomide. Then, he started maintenance treatment with cis-retinoic acid (100 mg/m(2)/day for 21 days). He remained asymptomatic for 34 months despite a follow-up brain MRI consistent with glioblastoma relapse 9 months before his death. Cis-retinoic acid may have contributed to prolong survival in this child with a probable biallelic mismatch repair syndrome.

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.

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.

Molecular Subgroup Is the Strongest Predictor of Medulloblastoma Outcome in a Resource-Limited Country.

PURPOSE: Medulloblastoma is composed of four clinically and prognostically distinct molecular subgroups (WNT, SHH, group 3, and group 4). However, the clinical implications of these subgroups in the context of the unique challenges of low- to middle-income countries are rarely reported. METHODS: We assembled an institutional cohort of children (3-18 years) diagnosed with medulloblastoma and treated in Jordan between 2003 and 2016. Tumors were subgrouped by NanoString and correlated with clinical and radiologic characteristics. RESULTS: Eighty-eight patients were identified (63% male); median age was 6.9 years (interquartile range 4.8-9.2) and median symptom duration was 6 weeks (interquartile range 4-11). Radiotherapy was implemented as standard-risk in 41 patients (47%) and high-risk in 47 patients (53%). Subgrouping revealed 17 WNT (19%), 22 SHH (25%), 21 group 3 (24%), and 28 group 4 tumors (32%). Median time between craniotomy and radiotherapy was 45 days (17-155); 44% of them > 49 days. Median duration of radiotherapy was 44 days (36-74). Seventy-two patients (82%) received chemotherapy afterward. With a median follow-up of 4.6 years (0.2-14.9), 5-year progression-free survival (PFS) and overall survival were 73.5% and 69.4%, respectively, with no statistically significant survival difference between standard-risk and high-risk patients. Metastasis was significant for overall survival (P = .011). Patients with SHH and group 4 tumors had very good PFS (83.4% and 87.0%, respectively) and those with group 3 tumors had dismal outcomes (PFS 44.9%), whereas WNT tumors had less-than expected PFS (70.5%). PFS was statistically significant in patients with nonmetastatic tumors receiving radiotherapy ≤ 49 days (P = .011), particularly group 3 tumors. CONCLUSION: Patients with SHH and group 4 medulloblastoma had excellent survival comparable with high-income countries. Compliance with treatment protocols and avoiding radiotherapy delays are important in achieving adequate survival in low- to middle-income country settings. Subgroup-driven treatment protocols should be considered in countries with limited resources.

Molecular correlates of cerebellar mutism syndrome in medulloblastoma.

BACKGROUND: Cerebellar mutism syndrome (CMS) is a common complication following resection of posterior fossa tumors, most commonly after surgery for medulloblastoma. Medulloblastoma subgroups have historically been treated as a single entity when assessing CMS risk; however, recent studies highlighting their clinical heterogeneity suggest the need for subgroup-specific analysis. Here, we examine a large international multicenter cohort of molecularly characterized medulloblastoma patients to assess predictors of CMS. METHODS: We assembled a cohort of 370 molecularly characterized medulloblastoma subjects with available neuroimaging from 5 sites globally, including Great Ormond Street Hospital, Christian Medical College and Hospital, the Hospital for Sick Children, King Hussein Cancer Center, and Lucile Packard Children's Hospital. Age at diagnosis, sex, tumor volume, and CMS development were assessed in addition to molecular subgroup. RESULTS: Overall, 23.8% of patients developed CMS. CMS patients were younger (mean difference -2.05 years ± 0.50, P = 0.0218) and had larger tumors (mean difference 10.25 cm3 ± 4.60, P = 0.0010) that were more often midline (odds ratio [OR] = 5.72, P < 0.0001). In a multivariable analysis adjusting for age, sex, midline location, and tumor volume, Wingless (adjusted OR = 4.91, P = 0.0063), Group 3 (adjusted OR = 5.56, P = 0.0022), and Group 4 (adjusted OR = 8.57 P = 9.1 × 10-5) tumors were found to be independently associated with higher risk of CMS compared with sonic hedgehog tumors. CONCLUSIONS: Medulloblastoma subgroup is a very strong predictor of CMS development, independent of tumor volume and midline location. These findings have significant implications for management of both the tumor and CMS.

Closing the survival gap: implementation of medulloblastoma protocols in a low-income country through a twinning program.

Successful twinning initiatives have been reported in childhood leukemia. Pediatric neuro-oncology requires a complex multidisciplinary approach and the feasibility of similar twinning programs is unknown. Twinning between King Hussein Cancer Center in Amman and the Hospital for Sick Children in Toronto started with e-mail communications, and subsequently included monthly videoconferences and exchanges between institutions. The outcome of 35 newly diagnosed medulloblastoma patients (22 high-risk and 13 average-risk) treated during this period is reported. The 3-year overall survival for average risk and high-risk patients was 100 and 81%, respectively. This experience suggests that twinning may facilitate the implementation of multidisciplinary neuro-oncology programs in low-income countries. Videoconferencing allows interactive exchanges with a significant learning impact.

Video-Teleconferencing in Pediatric Neuro-Oncology: Ten Years of Experience.

PURPOSE: The management of central nervous system tumors is challenging in low- and middle-income countries. Little is known about applicability of twinning initiatives with high-income countries in neuro-oncology. In 2004, a monthly neuro-oncology video-teleconference program was started between King Hussein Cancer Center (Amman, Jordan) and the Hospital for Sick Children (Toronto, Ontario, Canada). More than 100 conferences were held and > 400 cases were discussed. The aim of this work was to assess the sustainability of such an initiative and the evolution of the impact over time. METHODS: We divided the duration in to three eras according to the initial 2 to 3 years of work of three consecutive oncologists in charge of the neuro-oncology program at King Hussein Cancer Center. We retrospectively reviewed the written minutes and compared the preconference suggested plans with the postconference recommendations. Impact of changes on the patient care was recorded. RESULTS: Thirty-three sets of written minutes (covering 161 cases) in the middle era and 32 sets of written minutes (covering 122 cases) in the last era were compared with the initial experience (20 meetings, 72 cases). Running costs of these conferences has dropped from $360/h to < $40/h. Important concepts were introduced, such as multidisciplinary teamwork, second-look surgery, and early referral. Suggestions for plan changes have decreased from 44% to 30% and 24% in the respective consecutive eras. Most recommendations involved alternative intervention modalities or pathology review. Most of these recommendations were followed. CONCLUSION: Video-teleconferencing in neuro-oncology is feasible and sustainable. With time, team experience is built while the percentage and the type of treatment modifications change. Commitment and motivation helped maintain this initiative rather than availability of financial resources. Improvement in patients' care was achieved, in particular, with the implementation of a multidisciplinary team and the continuous effort to implement recommendations.

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.

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.

Cystic tumor in a 4 month old male.

Cystic choroid plexus tumor is a rare variant of choroid plexus papilloma (CPP), reported mostly in infants. It is associated with the development of acute hydrocephalus in many cases. The presence of atypical CPP has recently been recognized by the WHO as a grade II tumor with increased mitotic activity. We are reporting a case of a 3.5 month infant who presented with seizures and features of increased intracranial pressure. He was found to have cystic atypical choroid plexus papilloma.

Diffuse pontine glioma in Jordan and impact of up-front prognosis disclosure with parents and families.

For patients with diffuse pontine glioma, our institution offers local radiotherapy and supportive care only. The prognosis and do-not-resuscitate orders are discussed upfront with patients' parents. To investigate the effectiveness of this policy, we retrospectively reviewed records of patients with diffuse pontine glioma treated at the institution over a 49-month period. This study included 19 children (16 girls and 3 boys). The median age at diagnosis was 7 years. One patient remained alive at the end of the study, 2 were lost to follow-up, and 16 were confirmed dead. The median survival was 8.2 months. Do-not-resuscitate discussion was documented for 14 patients and successfully initiated for 11. None of those confirmed dead had been offered life support. Contrary to the common belief, our study showed that do not resuscitate should be addressed in Muslim patients with high-risk malignancies. We also found that diffuse pontine glioma warrants further study in developing countries.

Impact of telemedicine on pediatric neuro-oncology in a developing country: the Jordanian-Canadian experience.

BACKGROUND: Telemedicine is widely used in industrialized countries for educational purposes. Twinning experiences using telemedicine between institutions in industrialized and developing countries (DC) have been limited. Pediatric neuro-oncology is a complex multidisciplinary discipline that is underserved in most of DC and provides a model to test the feasibility of such tool for twinning purposes. METHODS: A computer, an EMLO visual presenter HV-7600SX document camera, and a TANDBERG 6000 model videoconference unit were used to present data. For connectivity, we used a six-channel ISDN telephone line. Each channel is 64 megabytes/sec. RESULTS: Between December 2004 and May 2006, 20 sessions of videoconference were held between King Hussein Cancer Center and the Hospital for Sick Children to discuss 72 cases of 64 patients with various brain tumors (5 patients were discussed twice and 1 patient four times). In 23 patients (36%), major changes from original plan were recommended on different aspects of the care. In 21 patients (91%), those recommendations were followed, with potentially significant positive impact on patients' care. CONCLUSIONS: Videoconferencing is a feasible and practical twinning tool in pediatric neuro-oncology with a potentially major impact on patient care.

Pediatric Burkitt's lymphoma: CT findings.

PURPOSE: To review and analyze all CT scans of the cases of Burkitt's lymphoma (BL) in children diagnosed in our institution. MATERIALS AND METHODS: A retrospective analysis of 33 children with BL between the years 2003 and 2005 seen in our institution was undertaken. Twenty-nine male and four female patients from age 3 to 16 years (with a mean age 5.9 years) were reviewed. RESULTS: The gastrointestinal tract was involved in 19 patients (57.5%), kidneys in 9 (27.2%), peritoneum in 8 (24.2%), liver in 4 (12.1%), spleen in 3 (9%), adrenals in 3 (9%), and pancreas in 1 patient (3%). Extra-nodal head and neck involvement was seen in eight patients (24.2%). Bone involvement in four (12.1%), lung in three (9%), heart in two (6%), skin in two (6%), and testis in one (3%) of these patients. Abdominal lymph nodes were enlarged in 21 children (63.6%), while cervical lymph nodes were enlarged in 8 (24.2%). CONCLUSION: CT proved to be an invaluable tool in the characterization of the disease processes in these children. In addition, it provided us with useful information about the anatomical distribution, patterns of involvement, as well as complications of BL.

Acute coronary artery air embolism following CT-guided lung biopsy.

CT-guided needle biopsy is a common procedure for obtaining a tissue diagnosis and consequently correctly managing patients. This procedure has many potential complications, ranging from simple pneumothorax or self-limiting hemoptysis to life-threatening pulmonary hemorrhage and air embolism. Though the latter is a rare complication of CT-guided needle biopsy, it has attracted a lot of interest. We report a case of right coronary air embolism resulting in myocardial infarction after a CT-guided percutaneous needle biopsy of the lung.