Discussion
After Ide
et al. reported the first suspected case of the regression of a primary intracranial germinoma [
3], several reports about the regression of primary intracranial germinomas were added to the literature [
1‐
5]. The patients in these cases received diagnostic radiation treatments, such as a cranial CT scan and/or angiography, without any known exceptions [
2‐
5]. As is evident from the literature, germinomas have high radiosensitivity [
6]. It is possible to shrink a germinoma with a single craniogram. In fact, shrunken germinomas demonstrate regrowth if carefully monitored [
3,
5]. Based on our experience of diagnostic irradiation and/or radiotherapy for the treatment of germinomas, and through our review of the literature about the regression of germinomas [
2‐
5], we have speculated that the shrinkage of the lesions in our case report was not a "spontaneous" regression but rather a diagnostic radiation-induced regression.
A second MRI, at 12 and eight days after the CT scan and DSA, respectively, confirmed the synchronous regression of the disseminated germinoma. Prior to confirmation of the synchronous regression, it was estimated that the patient had received a dose of diagnostic radiation of 27.0-41.4mGy (0.3-0.4Gy rounded). This figure was obtained as the sum of 23.4-37.8mGy (2.34-3.78cGy in the original text [
7]) of a single cranial CT scan [
7] and 3.6mGy of a single DSA (3.6mSv in the original text; Sv = Gy in X-ray) [
8].
Germinomas are so radiosensitive that they occasionally show regression after exposure to the radiation for diagnostic angiography [
9]. This shrinkage by diagnostic angiography enhances the radiosensitive nature of germinomas and supports the suggestion that the synchronous regression observed in our case report was not spontaneous but rather diagnostic radiation-induced.
Moreover, a correlative pathologic and imaging (CT and MRI) study reports the case of a 35-year-old man with a pineal germinoma who died unexpectedly of a massive pulmonary embolism on the eighth day of a course of radiation therapy after receiving a total dose of only 16Gy ( = 2Gy/day × 8 times). A histological study of the entire lesion in the serial sections of pathological specimen revealed no viable tumor cells [
6]. This report suggests that the highly radiosensitive nature of germinomas can result in a synchronous multiple regression of disseminated germinomas as a result of low-dose radiation.
Germinomas tend to be treated with a lower dose of radiation applied to a smaller volume of exposure field than those used with conventional radiotherapy of 40-55Gy [
10], using fractionated radiation therapy with a fraction size of <2.5Gy. The estimated dose of diagnostic radiation received by our patient before the regression of the germinoma was 0.3-0.4Gy, which is smaller than the fraction size of radiation therapy for germinomas ( = 2Gy).
This leads us to question whether previously-reported spontaneous regressions of germinomas really are "spontaneous". Significant percentages of previously-reported cases of the "spontaneous" regression of germinomas probably include radiation-induced regression, because the patients in all of these cases were exposed to diagnostic radiation; for example, plain X-ray films [
2], CT scan(s) [
3‐
5], and angiography [
2].
The periods from diagnostic irradiation to the detection of a regression in these cases from the literature are summarized in Table
1. The diagnostic radiation-induced regression of germinomas was observed between six and 56 days after diagnostic radiation (Table
1). This interval between diagnostic radiation and the regression of the tumors is a key point. To the best of our knowledge, no germinoma regressions have been reported in patients who had not previously undergone diagnostic irradiation.
Table 1
Summary of cases demonstrating regression of intracranial germinomas
| 21/M | Neurophypophysis | Larger than 20 mm | VP shunt | + | CT | 6 days | 2 months |
| 39/M | Pineal, IV ventricle | Larger than 20 mm | Tumor removal | + | X-ray film, cerebral angiography | 15 days from X-ray film, 6 days from angiography | N/A |
| 17/M | Pineal | 30 mm | VP shunt | none | 7 CTs | 56 days from 7th CT | N/A |
| 13/M | Neurophypophysis, Pineal | 13 mm, 20 mm | none | none | CT | 13 days | 3 weeks |
Our case report | 43/F | Neurophypophysis, Pineal, Llateral ventricle, IV ventricle | 32 mm, 10 mm, 6 mm, 9 mm | none | none | CT, cerebral angiography | 12 days from CT, 8 days from angiography | N/A |
Si
et al. reported the case of a patient with a central nervous system germinoma that showed a significant regression in size following surgery and the administration of dexamethasone, prior to the initiation of chemotherapy or irradiation [
11]. However, the patient underwent multiple cranial CT scans so, even in this case, we cannot be certain that the regression is not also diagnostic radiation-induced.
Conclusions
Clinicians should keep in mind that diagnostic radiation can induce the regression of intracranial germinomas and they should monitor germinoma lesions with minimal exposure to diagnostic radiation before diagnostic confirmation, and also before radiation treatment with/without chemotherapy begins. Regressions induced by diagnostic radiation may also indicate the high radiosensitivity of the lesion, which is key to an accurate diagnosis of germinoma. This provides a diagnostic and/or therapeutic clue and can help avoid radical resection.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
YY and IT collected the clinical data and drafted the manuscript. YY analyzed and interpreted the patient data regarding the germinoma and its radiosensitivity. SJ reviewed the literature. MN reported on the histopathological specimen. YF critically revised the manuscript. All authors read and approved the final manuscript.