Delayed Diagnosis in Children with Intracranial Germ Cell Tumors

doi:10.1016/j.jpeds.2013.06.024

The Journal of Pediatrics

Volume 163, Issue 5, November 2013, Pages 1448-1453

Portions of this study were presented during an oral presentation at the International Central Nervous System Germ Cell Tumor Symposium, April 17-19, 2013 in Cambridge, United Kingdom.

https://doi.org/10.1016/j.jpeds.2013.06.024 Get rights and content

Objective

To review symptoms and provider history in a large cohort of patients with germ cell tumors (GCTs) to highlight the variety of manifestations and assess the effect of delayed diagnosis on outcomes.

Study design

Patients treated for intracranial pure germinoma and nongerminomatous GCTs at Massachusetts General Hospital between 1998 and 2012 were included (n = 70). The primary outcome was time from onset of symptoms to diagnostic imaging. Delay was defined as an interval of ≥6 months.

Results

The median duration of symptoms before diagnostic magnetic resonance imaging was 6 months (range, 2 days to 72 months). Thirty-eight of the 70 patients (54%) had a delayed diagnosis. Patients with suprasellar tumors presented with symptoms related to endocrinopathies, and patients with pineal region tumors presented with symptoms related to hydrocephalus. Most of the patients were evaluated by a general pediatrician (49%) and/or pediatric subspecialists (66%) before diagnosis. Patients with delayed diagnosis saw a greater number of physicians before diagnosis (P = .006). The majority of patients (63%) with delayed diagnosis were seen by 2 or more physicians, and many (40%) were seen by 2 or more subspecialists. Progression-free survival was similar in the patients with delayed diagnosis and those without delayed diagnosis (P = .90), but the former were more likely to present with disseminated disease at diagnosis (34% vs 6%; P = .007).

Conclusion

A significant proportion of patients with GCT experience a delay in time to diagnosis, in some cases despite evaluation by general pediatricians and specialists. This delay increases the risk of disseminated disease.

Section snippets

Methods

All patients with an intracranial GCT treated with proton radiotherapy at the Massachusetts General Hospital (MGH) between 1998 and 2012 were included in this study. A total of 70 patients were identified. Disseminated disease was defined as the presence of noncontiguous disease in more than 1 anatomic location or tumor cells identified in the cerebrospinal fluid (CSF); patients with bifocal suprasellar or pineal disease were not included in this category. Tumors were classified as PG or NGGCT

Results

Thirty patients (43%) were diagnosed with NGGCT, and 40 (57%) were diagnosed with PG. The majority of primary tumors were located in the suprasellar region (28% of NGGCT and 40% of PG), followed by the pineal region (23% of NGGCT and 33% of PG), and multiple midline regions (18% of NGGCT and 26% of PG). The remaining patient presented with a posterior fossa mass. All isolated pineal region tumors occurred in male patients. A similar pattern was noted in patients with multiple midline tumors (13

Discussion

In our study cohort, patients with symptoms of ≥6 months duration were more likely to have disseminated disease. In addition, most patients, particularly those with delayed diagnosis, had undergone multiple specialist evaluations before diagnosis, likely owing to the subtle and insidious nature of their symptoms.

The median time to diagnosis of GCT in our cohort was 6 months. Other retrospective reviews of GCTs have reported an estimated duration of symptoms ranging from 39 days (median) to 8.4

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: R.S. is supported by the Doris Duke Clinical Research Fellowship. N.T. was on the medical advisory board of ProCure until 2008, and N.T.'s spouse continues to serve on medical advisory board of ProCure. The other authors declare no conflicts of interest.

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Original ArticleDelayed Diagnosis in Children with Intracranial Germ Cell Tumors

Objective

Study design

Results

Conclusion

Section snippets

Methods

Results

Discussion

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Lancet Oncol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Intracranial germ-cell tumors: natural history and pathogenesis

J Neurosurg

Malignant pineal germ-cell tumors: an analysis of cases from three tumor registries

Neuro Oncol

Primary intracranial germ cell tumors: a clinical analysis of 153 histologically verified cases

J Neurosurg

Primary intracranial germ cell tumors: pathology and treatment

Prog Exp Tumor Res

Combined chemotherapy and radiation therapy for central nervous system germ cell tumors: preliminary results of a Phase II study of the Japanese Pediatric Brain Tumor Study Group

Neurosurg Focus

Thiotepa-based high-dose chemotherapy with autologous stem-cell rescue in patients with recurrent or progressive CNS germ cell tumors

J Clin Oncol

Improved prognosis of intracranial non-germinoma germ cell tumors with multimodality therapy

J Neurooncol

Original Article
Delayed Diagnosis in Children with Intracranial Germ Cell Tumors