Wan-Yee Teo

Implications of Tumor Location on Subtypes of Medulloblastoma

Medulloblastoma (MB) comprises of four molecular subtypes, Sonic hedgehog (SHH), Wingless (WNT), Groups 3 and 4. WNT‐subtype MBs were found to arise from midline of the brainstem occupying the fourth ventricle while SHH‐subtype occupied the cerebellar hemisphere in a small subset of patients.

Neurological presentations of conversion disorders in a group of Singapore children

Background: Neurological presentations of conversion disorders in children are not uncommon. Conversion disorders mimicking neurological conditions constitute a group of underdiagnosed conditions.

Bony presentations of childhood haematological malignancy to the emergency room.

Aim:  Bony complaints are well‐recognised symptoms of childhood haematological malignancy. However, this elusive symptom complex of haematological malignancy is not easily recognised in the emergency room (ER) where musculoskeletal problems are frequent. This study reviews bony complaints of childhood haematological malignancy in the ER.

Preservation of KIT genotype in a novel pair of patient-derived orthotopic xenograft mouse models of metastatic pediatric CNS germinoma

Metastatic intracranial germinoma is difficult to treat. Although the proto-oncogene KIT is recognized as one of the most frequent genetic abnormalities in CNS germinoma, the development of new target therapeutic agents for CNS germinoma is hampered by the lack of clinically-relevant animal models that replicate the mutated or over-expressed KIT. CNS germinoma tumor cells from five pediatric patients were directly implanted into the brains of Rag2/severe combined immune deficiency mice. Once established, the xenograft tumors were sub-transplanted in vivo in mouse brains. Characterization of xenograft tumors were performed through histologic and immunohistochemical staining, and KIT mutation analysed with quantitative pyro-sequencing. Expression of putative cancer stem cell markers (CD133, CD15, CD24, CD44, CD49f) was analyzed through flow cytometry. Two patient-derived orthotopic xenograft (PDOX) models (IC-6999GCT and IC-9302GCT) were established from metastatic germinoma and serially sub-transplanted five times in mouse brains. Similar to the original patient tumors, they both exhibited faint expression (+) of PLAP, no expression (−) of β-HCG and strong (+++) expression of KIT. KIT mutation (D816H), however, was only found in IC-9320GCT. This mutation was maintained during the five in vivo tumor passages with an increased mutant allele frequency compared to the patient tumor. Expression of putative cancer stem cell markers CD49f and CD15 was also detected in a small population of tumor cells in both models. This new pair of PDOX models replicated the key biological features of pediatric intracranial germinoma and should facilitate the biological and pre-clinical studies for metastatic intracranial germinomas.

Langerhans cell histiocytosis - a mimicker of tuberculosis of the spine.

with paracetamol, while the treatment with carbamazepine improved her neurological impairment, which when associated to a dental conservative approach (use of a flat nipple to avoid the impact of the teeth against the tongue associated to the topical application of a chlorhexidine 0.5% and hyluronic acid-based gels), led to a clinical amelioration of the ulcer (Fig. 1d) with an improvement of feeding and a gradual gain of weight. RFD is a rare, oral, ulcerative condition described by Antonio Riga, an Italian physician in 1881. The oral ulcer is characterized by continuous traumatic injuries produced by natal or neonatal teeth, usually lower incisors, resulting in tongue ulceration. This form is called ‘precocious or early RFD’, and appears before 6 months of age, a period in which the child is edentulous. However, a ‘late RFD’ appearing in 6 months of age or in older children is also described. It is not due to a precocious teeth eruption, but, as in our case, to neurological or developmental disorders in a child with normal chronology of dental eruption. Hence, this latter disorder may be the initial presentation of some serious underlying medical problems, as Lesch–Nyhan syndrome, familial dysautonomia and/or other neurological disorders as parasomnia, hereditary chin trembling and facio-mandibular myoclonus that may cause nocturnal tongue biting. From a point of view of its clinical manifestation, the differential diagnosis of RFD includes granular cell tumour, myofibroma, eosinophilic granuloma and other traumatic ulcers. Malignancies (sarcoma and lymphoma) and infectious diseases (acquired/congenital syphilis, tuberculosis and ulcerative fungal infections) must also be ruled out. Because the precocious extractions may have a negative impact on the dentoalveolar growth of the children, the treatment of choice of RFD should be conservative (as in our case), reserving the surgical approach, with the extraction of the teeth and subsequent application of a space maintainer, only in case of non-healing in conservative treatment.

The curious case of ileocolic intussusception

A 6-year-old girl presented with intermittent generalised abdominal pain for 2 days, associated with recurrent episodes of vomiting, without evidence of bloody, redcurrant stools or diarrhoea. An abdominal ultrasound revealed with a target-like mass in the right lower quadrant (Fig. 1a) consistent with an ileocolic intussusception. She underwent a successful air reduction, but developed a fever of 38.9°C and was admitted for observation. Initially, she was well appearing; however, she developed right upper and lower quadrant pain. An upright abdominal radiography was performed to rule out perforation or recurrence of intussusception. There was no evidence of perforation, but the abdominal X-ray demonstrated opacity in the right lower quadrant (Fig. 1b). A repeat abdominal ultrasound revealed a dilated appendix, with significant inflammation and surrounding fluid suggestive of a ruptured appendix. She underwent a laparoscopic appendectomy during which she was confirmed to have a perforated retrocecal appendicitis. Postoperative course was notable for a paralytic ileus, which eventually resolved. Intussusception is the most common cause of intestinal obstruction in infants 6–36 months of age. Approximately 90% are younger than 2 years. Intussusception is less common before 3 months and after 6 years of age. Most childhood cases are idiopathic while adult cases are frequently associated with a pathologic lead point. This case highlights the rare occurrence of acute appendicitis as a possible lead point in ileocolic intussusception, in an atypical age group for childhood intussusception (>2 years old). Few rare cases of ileocolic intussusception complicating appendicitis have been described, where the collection of appendiceal pus served as a lead point. In this patient, the appendix may have developed an ischaemic perforation as a result of entrapment within the intussusceptum. An alternative explanation could be that the patient had appendicitis all along, with ultrasound imaging picking up a transient intussusception. In a broader perspective, this unusual case perhaps illustrates the potential dangers of the Occam’s razor in medical problemsolving, where a single diagnosis with the least competing hypotheses is assumed to be the most possible explanation for the patient’s signs and symptoms. As in this case, maintaining a suspicious mind for convoluted hypotheses when the patient deviated from an expected clinical course led to an early diagnosis and good patient outcome.