Faculty Bibliography

Surgery plays an important part in the overall management of primary central nervous system (CNS) germ cell tumors. While the general surgical objectives in patients with these neoplasms are similar to those with other types of CNS tumors, to obtain an accurate histopathologic diagnosis and to contribute towards improving patient survival the unique features of germ cell tumors have necessitated novel treatment strategies. Pure germinomas are exquisitely radiosensitive, and prior studies have shown no survival benefit from radical resection of such lesions. However, a significant proportion of CNS GCTs contain admixtures of nongerminomatous GCT (NGGCT) elements and are less responsive to aggressive chemotherapy and irradiation. Biopsy of these malignant GCTs carries the risk of histologic sampling error. Nevertheless, a proportion of NGGCTs produce tumor markers detectable in serum or CSF and may be accurately diagnosed without surgical intervention. Although the role of radical surgical resection has not been definitively demonstrated in the literature, recent data from an international cooperative trial suggest a survival benefit from radical resection of localized NGGCTs. Lastly, increasing experience has supported the role of delayed resective ('second-look') surgery for patients with negative tumor markers but residual radiographic abnormalities after initial chemotherapy. Resection of such lesions has typically yielded necrosis or teratoma, which may be cured by surgical resection, and obviated the need for additional chemotherapy or irradiation

Primary germ cell tumors of the central nervous system are rare neoplasms, accounting for no more than 2% of all malignancies in children and young people under 20 in the Western hemisphere. They have unique features related to age at diagnosis and sites of origin, as well as race and gender predilection. Prognosis has been clearly shown to be strongly related to pathological classification as either pure germinoma or nongerminomatous germ cell tumor, although many of these lesions are comprised of mixed elements. The presence of serum or cerebrospinal fluid tumor marker elevation has been an essential determinant of response to treatment. Because of the deleterious effects of irradiation on the immature nervous system, investigators have used chemotherapeutic strategies that either reduce or eliminate radiation therapy. In this article, we review the most recent advances in therapy for CNS germ cell tumors in the pediatric population and highlight the importance of cooperative trials in this setting.

The regionalization of the neural tube along the anteroposterior axis is established through the action of patterning signals from the endomesoderm including the organizer. These signals set up a pre-pattern which is subsequently refined through local patterning events. The midbrain-hindbrain junction, or isthmus, is endowed with such an organizing activity. It is able to induce graded expression of the Engrailed protein in the adjacent mesencephalon and rhombencephalon, and subsequently elicits the development of tectal and cerebellar structures. Ectopically grafted isthmus was also shown to induce Engrailed expression in diencephalon and otic and pre-otic rhombencephalon. Fgf8 is a signalling protein which is produced by the isthmus and which is able to mimic most isthmic properties. We show here that the isthmus, when transposed to the level of either rhombomere 8 or the spinal cord, loses its ability to induce Engrailed and cerebellar development in adjacent tissues. This is accompanied by the down-regulation of fgf8 expression in the grafted isthmus and by the up-regulation of a marker of the recipient site, Hoxb-4. Moreover, these changes in gene activity in the transplant are followed by a transformation of the fate of the grafted cells which adjust to their novel environment. These results show that the fate of the isthmus is not determined at 10-somite stage and that the molecular loop of isthmic maintenance can be disrupted by exogenous signals

Cephalic molding at birth has been traditionally felt to be benign, resulting in only a transient and self-correcting cranial deformity. However, we report a 6-month-old infant who presented with extensive cephalic molding at birth in combination with persistent brachyturricephaly from unilateral coronal synostosis and occipital deformation. Helmet therapy over a 3-month period failed despite patient compliance and numerous adjustments. Intracranial hypertension developed, as documented by multiple occipital bony erosions on computed tomographic scan and by an elevated direct intracranial pressure reading. The cranial vault asymmetry was corrected in two surgical stages: (1) occipital bar advancement, temporoparietal bone remodeling, and midline sagittal strip compression to reduce vertical height, followed in 3 months by (2) fronto-orbital advancement and remodeling

Growing skull fractures (GSF) are rare in adults. We report the case of an adult who was found to have a GSF 50 years after head trauma. This case highlights the need to consider GSFs in the differential diagnosis of adults with intradiploic skull lesions