Janet M. Yoon

Modifying the soil to affect the seed: role of stromal-derived matrix metalloproteinases in cancer progression

In the 1980s, as the importance of matrix metalloproteinases (MMPs) in cancer progression was discovered, it was recognized that in most tumors these proteases were abundantly and sometimes exclusively expressed not by tumor cells, but by normal host-derived cells like fibroblasts, vascular endothelial cells, myofibroblasts, pericytes or inflammatory cells that contribute to the tumor microenvironment. Later experiments in mice deficient in specific MMPs revealed that host-derived MMPs play a critical role not only in tumor cell invasion, but also in carcinogenesis, angiogenesis, vasculogenesis and metastasis. Tumor cells secrete many factors, cytokines and chemokines that directly or indirectly increase the expression of these MMPs in the tumor microenvironment where they exert extracellular matrix (ECM) degrading and sheddase activities. The knowledge of the complex role that stromal-derived MMPs play in the interaction between tumor cells and stromal cells should allow us to consider specific windows in cancer treatment when MMP inhibition could have a valuable therapeutic effect.

Treatment of infantile choriocarcinoma of the liver.

Primary choriocarcinoma of the liver is an extremely rare childhood malignancy frequently associated with clinical instability at initial presentation. It often mimics other benign and malignant childhood liver tumors. Prompt diagnosis and initiation of treatment are necessary to attain a successful outcome. We describe a critically ill infant with metastatic choriocarcinoma whose diagnosis was based on radiographic and tumor marker findings, without an initial biopsy, and her successful management with neo‐adjuvant chemotherapy and delayed surgery. She is currently in continuous remission 24 months from diagnosis. Pediatr Blood Cancer 2007;49:99–102.

Anti‐tumor activity of the HSP90 inhibitor SNX‐2112 in pediatric cancer cell lines

HSP90 plays a central role in stabilizing client proteins involved in malignant processes. SNX‐2112 is an orally administered potent HSP90 inhibitor that has demonstrated pre‐clinical anti‐tumor activity in adult malignancies. As many childhood tumors depend upon HSP90 client proteins, we sought to test the pre‐clinical efficacy of SNX‐2112 in a panel of pediatric cancer cell lines both as a single‐agent and in combination with cisplatin (CP).

Glioblastoma multiforme arising from dysembryoplastic neuroepithelial tumor in a child in the absence of therapy.

Dysembryoplastic neuroepithelial tumors (DNETs) are considered as low-grade tumors commonly associated with intractable seizures. We report a case of an unusual hemispheric DNET in a young child presenting with new-onset focal seizures. The tumor was notable for its atypical neuroimaging features and very rapid malignant transformation into a glioblastoma multiforme in the absence of radiation or chemotherapy, 1-year postdiagnosis. Our case highlights the malignant potential of atypical DNETs in the absence of therapy.

Severe vincristine-induced polyneuropathy in a teenager with anaplastic medulloblastoma and undiagnosed Charcot-Marie-Tooth disease.

Severe neuropathy is a known adverse effect of vincristine in patients with Charcot-Marie-Tooth disease (CMT). We present the case of a 16-year-old girl with anaplastic medulloblastoma treated with gross total resection and high-dose craniospinal radiation with adjuvant vincristine chemotherapy who developed acute-onset severe quadriplegia and vocal cord paralysis. Vincristine and radiation therapy were discontinued. Although her neuropathy slowly improved over several weeks, she developed metastatic extraneural medulloblastoma and died 5 months after diagnosis. Subsequent genetic testing revealed previously asymptomatic and undiagnosed CMT1A. Our case highlights the importance of early recognition of acute vincristine neurotoxicity that should raise suspicion of an underlying hereditary neuropathy.

A diffuse intrinsic pontine glioma in a neonate diagnosed by MRI

A 4-day-old full-term girl with a maternal history of polyhydramnios during the third trimester was transferred from an outside nursery for hypotonia, poor feeding and abnormal respirations. Barium swallow evaluation prior to transfer revealed laryngeal penetration with silent aspiration and absent cough reflex. On physical examination the infant had stridor, increased oral secretions, axial hypotonia, right esotropia and facial weakness. MRI of the brain (figure 1) demonstrated a large tumour centred in the …

Diagnostic challenges of bHCG interpretation following gonadectomy in a patient with Swyer syndrome

Pediatric germ cell tumors (GCTs) are rare tumors with a favorable prognosis. Tumor markers are utilized for screening, confirming diagnosis, predictingprognosis and response to therapy, andmonitoring for recurrence. A failure of tumor markers to normalize after treatment can be a predictor of poor response to therapy and poor prognosis.1 Many factors should be considered when interpreting tumor markers including current treatment, the effects of age and menopause, tumor marker metabolism, co-existing disease, and the overall health of the patient.2 We present a case where beta-human chorionic gonadotropin (bHCG) failed to normalize in a patient with Swyer syndrome following gonadectomy. Our previously healthy, prepubertal 13-year-old patient presented with abdominal pain. Ultrasound revealed a left adnexal mass without Doppler blood flow concerning for ovarian torsion. Surgical exploration revealed torsion of the left gonad, which was large and viable; the right gonad was small and yellow with a streaked mullerian structure, and the uterus was small. Follow-up laboratories revealed elevated follicle-stimulating hormone (FSH) of 74.81 mIU/ml (reference range for age: 0.87–9.16mIU/ml), elevated bHCGof 25 IU/l (reference range: <1.0 IU/ml), elevated luteinizing hormone (LH) of 34.5 mIU/ml (reference range for age: 0.04–10.80 mIU/ml) and a 46XY karyotype consistent with pure gonadal dysgenesis or Swyer syndrome. Swyer syndrome affects normal sexual development. Patients are phenotypically female, with normally developed vagina and uterus; however, they have amale karyotype. There is gonadal dysgenesiswith

Novel PTCH1 Mutation in a Young Child With Gorlin Syndrome and Medulloblastoma.

Gorlin syndrome (also known as nevoid basal cell carcinoma syndrome) is a rare autosomal dominant disorder with a high degree of penetration caused by a germline mutation in the PTCH1 gene.[1] About 70–80% of patients with Gorlin syndrome will have an affected parent, and about 20–30% will have new spontaneous mutations.[1] Gorlin syndrome has a prevalence of 1/57,000 to 1/256,000 with diagnosis based upon clinical findings as well as the presence of a mutation in the PTCH1 gene.[1–3] We report the case of a pediatric patient with Gorlin syndrome and nodular desmoplastic medulloblastoma harboring a novel PTCH1 gene mutation who had diffuse leptomeningeal spread in the absence of adjuvant therapy. A 4-year old previously healthy male presented to the emergency room after a several month history of abnormal eyemovements. Evaluation showed bilateral papilledema, esotropia, and mild abducens nerve palsy. A computed tomography (CT) scan

Atypical Teratoid Rhabdoid Tumor in a Teenager with Unusual Infiltration Into the Jugular Foramen

BACKGROUND Atypical teratoid rhabdoid tumor is a rare malignant neoplasm that represents 1%-2% of all pediatric central nervous system tumors. Immunohistochemistry plays an important role in establishing the diagnosis with a loss of INI-1 staining in tumor cells. In this case report, we describe a teenager with an unusual presentation and pattern of infiltration of the tumor. CASE DESCRIPTION A 13-year-old boy presented with a history over several months of progressive nausea, weight loss, and hoarseness of voice associated with multiple lower cranial nerve palsies on neurologic examination. Magnetic resonance imaging revealed a large heterogeneously enhancing extra-axial neoplasm with extension and bony expansion of the jugular foramen. After near total resection, neuropathology demonstrated the absence of INI-1 expression consistent with a diagnosis of atypical teratoid rhabdoid tumor. CONCLUSIONS This case highlights the diverse clinical presentation and infiltrative potential of atypical teratoid rhabdoid tumors, thus expanding the differential diagnosis of extra-axial tumors invading the jugular foramen.

Secondary Hemophagocytic Lymphohistiocytosis in a Patient With Favorable Histology Wilms Tumor.

Secondary hemophagocytic lymphohistiocytosis (HLH) is most commonly associated with malignancy, infection, or an underlying autoimmune disorder. Malignancy-associated hemophagocytic syndrome is responsible for most secondary HLH cases, but it has not been well described in children. We present a case of a 4-year-old female with favorable histology of Wilms tumor who developed secondary HLH after unsuccessful resection of the tumor and initiation of chemotherapy.