Intracranial calcified masses are usually associated with slowly progressive benign tumors (e.g., oligodendroglioma and meningioma), infectious diseases (e.g., tuberculosis, fungal infection, cysticercosis), and metabolic disorders (e.g., hyperparathyroidism).

Calcified metastases to the brain have been described in patients with squamous cell carcinoma of the lung,⁷⁾ adenocarcinoma of the lung,³⁾ sarcoma of the mediastinum,¹³⁾ squamous cell carcinoma of the cervix,⁴⁾ adenocarcinoma of the pancreas,¹⁾ and non-Hodgkin's lymphoma.¹⁶⁾ Only four cases of calcified metastases to the brain arising from a primary ovarian carcinoma have been described.^2,6,11)

Generally, calcified brain tumors in those cases remained stable and did not progress. In fact, these patients had relatively benign clinical courses and prolonged survival. All four cases were multiple lesions and the interval between diagnosis of ovarian cancer and brain metastases was 3–12 months.

The present report describes a case of a patient with a single large cerebellar calcified metastatic tumor mimicking meningioma that arose from a primary ovarian cancer. This patient also had a relatively benign clinical courses and favorable survival, and the latent period was 10 years, which was longer than that in previous reported cases.

A 33-year-old woman had a notable history of ovarian cancer diagnosed 10 years prior that was treated by surgical resection and adjuvant systemic chemotherapy. During a screening examination, a calcified cystic lesion was incidentally noted in the right cerebellar hemisphere on computed tomography (CT) (Fig. 1A). The patient declined any treatment for the presumed cerebellar tumor and instead elected for serial follow-up. The size of the tumor gradually increased, while she was asymptomatic (Fig. 1B). Two years after the initial CT, she presented with headache and positional vertigo, and CT showed enlargement of the calcified tumor and hydrocephalus (Fig. 1C). Magnetic resonance imaging (MRI) showed a lesion that was isointense on T₁-weighted images and heterogeneously hyperintense on the T₂-weighted image with slight heterogeneous enhancement with gadolinium (Fig. 2A–C). Tonsillar herniation with obstructive hydrocephalus was also recognized (Fig. 2D).

Informed consent was obtained, and right lateral suboccipital craniotomy was performed. The tumor was located subpially and appeared as a well-demarcated elastic hard mass that could be easily distinguished from the surrounding parenchyma. The tumor was gross totally removed. Histological findings revealed that the tumor cells were arranged in an acinar formation with psammomatous calcification in the stroma with atypical and mitotic tumor cells. The lesion was compatible with a diagnosis of serous mucinous adenocarcinoma (Fig. 3). MIB-1 index was 3% (data not shown) (MIB-1: Mindbomb E3 ubiquitin protein ligase 1). Postoperatively, the patient experienced improvement in her symptoms of headache and vertigo, and her postoperative course was uneventful. Postoperative CT and MRI revealed that the tumor was gross totally removed and demonstrated marked improvement in the tonsillar herniation and obstructive hydrocephalus (Figs. 4, 5). She got discharged two days after surgery. Subsequently, she received whole brain irradiation.

Calcification of metastatic brain tumors is very rare and tends to occur in the basal ganglia and cerebellum, which are rich in endogenous iron and calcium.⁹⁾ At least two different mechanisms have been postulated to explain marked calcification of metastatic brain tumors.^6,10,12) First, reduced metabolism of degenerative or necrotic tissue can interrupt CO₂ production, making the lesions more alkaline than the surrounding tissues, thereby promoting calcification. Alternatively, calcification might be mediated by an increase in local alkaline phosphatase levels in degenerative tissues. In the presence of hypoxia, the equilibrium of extracellular calcium fails, resulting in an influx of calcium into the cell and subsequent calcium phosphate deposition. In a stable microenvironment, calcium phosphate may eventually be converted into calcium hydroxyapatite, and crystal proliferation can follow, with the extension of calcification into the extracellular space. Calcification, therefore, may follow cell death and may be promoted by the presence of alkaline phosphate.

Generally, the differential diagnosis between metastatic brain tumors and benign intracranial tumors, including meningioma and oligodendroglioma, is exceedingly important, especially for treatment planning.¹⁴⁾ Calcified brain tumors are occasionally misdiagnosed in the absence of edema and contrast enhancement, resulting in a delay in diagnosis and/or treatment.^5,8,11)

In the present case, a patient with stage IIIc ovarian cancer treated with surgery and chemotherapy developed cerebellar metastasis 10 years after the initial diagnosis of her cancer. The cerebellar tumor was incidentally discovered by CT and, at the patient's preference, was followed conservatively. Initially, the tumor was considered to be a benign tumor, possibly a meningioma. However, slow growth of the tumor ultimately resulted in headache and vertigo due to tonsillar herniation and obstructive hydrocephalus at 2 years after detection of the brain lesion. On this basis, emergent surgical management was elected.

A previous study¹⁷⁾ using serial brain CT scans reported that size of the calcified metastatic brain tumors tended to increase at a rate slower than ordinary brain metastasis and can thereby be misinterpreted as meningioma.

Calcified brain tumors tend to remain quiescent without progression.^7,10) Considering the long periods of time required to develop calcium deposits, calcification appears more frequently in benign cysts or slow-growing tumors. On the other hand, loss of calcification indicates accelerated growth of malignant tumors.⁵⁾ Calcified meta-static brain tumors are very rare, but are also clinically important, as a delay in diagnosis and treatment can adversely impact survival.

Cancers arising in the lungs, colon, and breast are the most frequently reported primary cancer types that result in calcified intracranial metastases, while brain metastasis from ovarian cancer is comparatively rare. In the review of metastatic brain tumors arising from a primary ovarian cancer in the Department of Obstetrics and Gynecology at our institution, this phenomenon was noted in only 10 cases (0.24%) of 4,158 patients with ovarian cancer seen at our center over a period of 8 years (Table 1). In addition, only four cases of calcified brain metastasis arising from ovarian cancer have been reported thus far^2,6,11) (Table 2). The interval between treatment of the primary ovarian cancer and onset of the metastatic brain lesion in these cases ranged from several months to 10 years.¹⁵⁾ In our institution, the mean interval between diagnosis of the primary ovarian cancer and diagnosis of meta-static brain tumors was 1,271 days (3.5 years) (Table 1). As shown in Table 1, 6 (75%) of 8 cases of metastatic brain tumors arising from ovarian cancer in our institution had a single intracranial lesion. In contrast, all cases of calcified metastatic brain tumors arising from ovarian cancer in the literature had multiple lesions (Table 2), which favored the use of whole brain radiation therapy as the preferred therapeutic modality in those cases. Thus, the present case of a patient with a single calcified metastatic cerebellar tumor arising from ovarian cancer is extremely rare.

Due to simple statistics, increase in survival in response to advances in chemotherapy may actually result in an increase in the incidence at which subsequent brain metastases (due to cancer relapse) are diagnosed. Interestingly in the present case, the interval between the initial diagnosis of the brain lesion and treatment of the cerebellar tumor was 2 years, which suggests a relatively indolent tumor phenotype that is similar to that seen for meningioma. Therefore, calcification might be an indicator of a relatively long survival in the case of metastatic tumor, provided the primary cancer is controlled.

In conclusion, complete tumor resection may be an acceptable approach for patients with calcified metastatic tumors both for therapeutic considerations and to obtain tissue for confirmation of histopathological diagnosis. Metastatic brain tumors can be calcified, and not only ovarian cancer but also other cancers should be considered within the differential diagnosis of calcified intracranial lesions to avoid any delay in diagnosis or treatment.