Case report Calcified brain metastatic adenocarcinoma: A case report and review of the literature The Neuroradiology Journal 0(00) 1–5 ! The Author(s) 2018 Article reuse guidelines: sagepub.com/journals-permissions DOI: 10.1177/1971400918805184 journals.sagepub.com/home/neu Eshagh Bahrami, Morteza Taheri and Mohsen Benam Abstract Introduction: Calcification in brain metastasis occurs rarely so it is reported in approximately 1% of surgical and 6.6% of autopsy specimens. Here we report a new case of brain metastasis with calcification. Case presentation: A 44-year-old woman presented with a generalized tonic–clonic seizure with no neurological deficit on physical examination. Brain imaging demonstrated a hyperdense lesion on computed tomography scan and hyposignal and rim enhancement on T1, T2 and T1 with gadolinium injection sequence images in the right parieto-occipital lobe. Intraoperatively, there was a well-defined solid homogenous calcified mass within brain parenchyma. The lesion that resembled a meningioma was totally resected. The histopathological examination revealed metastatic adenocarcinoma. Conclusion: Metastatic brain lesions should be in the differential diagnosis of a solitary calcified brain mass, although it occurs rarely. It is important to differentiate it radiologically from intralesional haemorrhage. Keywords Calcified brain mass, metastatic adenocarcinoma, colon cancer Introduction Calcification is a physiological process in the brain and also in the choroid plexus and pineal gland. As a pathological process, it occurs in vascular, neoplastic, inflammatory and metabolic diseases.1 Brain tumours such as meningioma and oligodendroglioma, infectious processes such as tuberculosis, fungal and cysticercosis and metabolic diseases such as hyperparathyroidism are the most common clinical situations associated with an intracranial calcified mass.2 Calcification in brain metastasis occurs rarely so it is reported in approximately 1.1% of surgical and 6.6% of autopsy specimens.3 Here we report a new case of brain metastasis with calcification. Case presentation A 44-year-old woman presented with a generalized tonic–clonic seizure 3 days before the admission. Physical examination showed no neurological deficit. Brain computed tomography (CT) scan demonstrated a hyperdense lesion in the right parieto-occipital lobe (Figure 1). Brain magnetic resonance imaging (MRI) demonstrated a well-defined lesion in the right parieto-occipital lobe that was hyposignal on T1 and T2 associated with rim enhancement on T1 with gadolinium injection sequence images (Figure 2). There was moderate vasogenic oedema around the lesion. Laboratory tests and chest X-ray were normal. After right parietooccipital craniotomy, opening the dura by the transcortical approach, there was a welldefined solid homogenous calcified mass within the brain parenchyma. The lesion that resembled a meningioma was totally resected. The histopathological examination revealed metastatic adenocarcinoma, most probably from the colon region. The patient was referred to an oncologist for further work-up and treatment. After scalp wound healing, the patient received adjuvant cranial radiotherapy for local control of the disease. After a thorough work-up, the large intestine tumour (caecal adenocarcinoma) was affirmed, and she underwent systemic chemotherapy for treatment. At the last follow-up 4 months after surgery, she had completed the adjuvant radiotherapy and was receiving systemic chemotherapy, she had no neurological signs and symptoms and no evidence of recurrence on brain imaging. Discussion Metastatic brain lesions can be solitary or multiple. On CT scan, they can be hypo, iso or hyperdense Rasool Akram Hospital, Iran University of medical Sciences, Iran Corresponding author: Morteza Taheri, Department of Neurosurgery, Rasool Akram Hospital, Niyayesh St., Sattarkhan St., Tehran, Iran. Email: drtaheri38@yahoo.com 2 compared to the adjacent brain parenchyma. However, in the setting of metastatic brain melanoma and intralesional haemorrhage, CT scan demonstrated a hyperdense lesion.4 Haemorrhage into the metastasis can make the diagnosis of calcified mass challenging. Some attention helps to differentiate them from each other. First, attenuation values for haemorrhage are usually 35–55 Hounsfield units, but two studies demonstrated Hounsfield units of 50–105 and 86 for calcification within metastasis.5 Second, it is more likely that punctuate and curvilinear hyperdensity is metastasis, but differentiation in the setting of amorphous hyperdensity is difficult. Third, calcification is usually unchanged or progresses very slowly during follow-up, but haemorrhage-induced hyperdensity resolves over time.5 Brain metastasis does not generally calcify. When a metastasis shows calcification other diagnoses should be considered.4 Figure 1. The axial brain computed tomography scan shows a hyperdense mass with surrounding hypodensity. The Neuroradiology Journal 0(00) Intracranial calcification can be physiological as occurs in the basal ganglia and cerebellum due to the rich source of endogenous iron and calcium,2 or can be associated with the pathological process as a slowly progressive glioma; and in infectious diseases such as tuberculosis, fungal infection and cysticercosis; and occasionally, with cystic lesions due to the slowing process of calcium deposition.6 Although the exact mechanism of calcification into metastatic lesions is unknown, there are two theories: first, degenerative and necrotic tissue decreases metabolism, resulting in disruption of carbon dioxide production, ultimately making the lesion alkaline compared to the surrounding parenchyma, consequently facilitating the deposition of calcium in alkaline tissue. Second, necrotic and degenerative tissue has a low level of oxygen that results in the influx of calcium into the intracellular space and a high level of alkaline phosphatase resulting in calcium phosphate deposition.2 Because calcification usually occurs in the necrotic part of the lesion, significant enhancement does not occur in this part so the peripheral non-necrotic part only shows marked enhancement.5 The most common intracranial masses with calcification includes oligodendroglioma, low-grade astrocytoma, craniopharyngioma, meningioma, pineal gland tumours and ependimoma.6 Although lung, breast, colon and ovaries are the most common primary site of cancer resulting in calcified brain metastasis, however, cases have been reported of calcified brain metastasis with an origin of squamous cell carcinoma and adenocarcinoma of the lung, sarcoma of the mediastinum, squamous cell carcinoma of the cervix, adenocarcinoma of the pancreas and non-Hodgkin’s lymphoma.2 In the present case, the brain lesion was a solitary mass, hyperdense on CT scan associated with vasogenic oedema. Intralesional haemorrhage was the most differential diagnosis versus calcification. With the help of Figure 2. (a) Axial T1; (b) axial T2; and (c) T1 with gadolinium demonstrates the intra-axial lesion. 62 68 Inomata et al.15 12 Nakase et al.19 9 Bhatoe and Gill14 11 16 F 33 Kawamura et al.2 10 70 F 46 Stadnik et al.18 F 29 Ohmoto et al.13 9 15 F 58 Yamazaki et al.12 8 60 M 4.5 Tomita and Larsen11 7 30 M 57 Tashiro et al.3 6 Fatehi et al.16 M 55 Yamada and Suzuki10 5 Michail et al.17 F 32 Gaze et al.9 4 13 M 60 Fukuda et al.8 3 14 w 52 Ricke et al.1 2 F F F M F F M 61 Callizo et al.7 1 Sex Age Study Row Small cell carcinoma of lung – Colorectal carcinoma Breast cancer Lung adenocarcinoma Non-Hodgkin’s lymphoma Ovarian cancer Lung cancer – – Undifferentiated sarcoma – Diffuse, large cell non-Hodgkin’s lymphoma Squamous carcinoma of cervix Lung adenocarcinoma Ovarian cancer – Previous malignancy – Peripheral calcification – – Scattered – – Linear – Scattered punctate – Conglomerate Nodular Punctate Nodular Circular/ irregular Punctate/curvilinear comma-like scattered Features of calcification Table 1. Previous studies reporting cases of calcified brain metastasis. Disseminate Post fossa Frontoparietal Disseminate Disseminate Frontal lobe Cerebellar hemisphere Frontal lobe Frontal lobe Disseminate Parietal/ cerebellum Corpus callosum Thalamic region Temporoparietal Disseminate Disseminate Disseminate Location Multiple Multiple Solitary Multiple Multiple Solitary Solitary Solitary Solitary Multiple Two lesiosn Solitary Solitary Solitary Multiple Multiple Multiple Number of lesions – Surgery Surgery – – Biopsy Surgery Surgery Surgery Biopsy Surgery Surgery – Surgery – Biopsy – Procedure Death/1 year – – – Death/1 year Death/12 days Death/3 years & 3 months Survived/2 years & 3 months Death/8 months –/3 Months Death/12 months Survived/12 months Death/10 months – – – Outcome/ follow-up duration Autopsy Histopathology Histopathology – Autopsy Histopathology Histopathology Histopathology Histopathology Histopathology Histopathology Histopathology – Histopathology Autopsy Histopathology Autopsy Confirm after (continued) Small cell carcinoma of lung Papillary cystadenocarcinoma Adenocarcinoma of colorectal Lung adenocarcinoma/ leptomeningeal adenocarcinoma – Non-Hodgkin’s lymphoma Serous mucinous adenocarcinoma Adenocarcinoma Adenocarcinoma of lung Metastatic adenocarcinoma of the lung Metastatic undifferentiated sarcoma Metastatic squamous cell carcinoma/ unknown origin – Squamous carcinoma of cervix Papillary adenocarcinoma lung Papillary carcinoma of the ovaries Acinar cell carcinoma of the pancreas Histopathology Bahrami et al. 3 M 50 21 38 to 72 48 Teksam et al.21 Anand and Potts5 Fernandez et al.22 Our study 19 20 21 22 44 M 62 Hwang et al.20 18 F M 5F/ 2 M M F 50 Eom and Kim6 17 Sex Age Study Row Table 1. Continued Curvilinear Amorphous Punctate Amorphous Lung Colon Breast Colon – Amorphous Round Curvilinear Oesophagus Osteosarcoma of mandible Punctate Punctate – – – – Features of calcification Lung, breast Lung Osteosarcoma Squamous cell carcinoma of the lung – Lung cancer Previous malignancy Parietal lobe Centrum semiovale Frontoparietal Supratentorial Frontal lobe Cerebellum Cerebellum Temporal lobe Supra/infra-tentorial Tepmoroparieto-occipital Temporal lobe Parietal/temporal/ corpus callosum Frontal lobe Location Solitary Two Solitary Multiple Solitary Solitary Solitary Solitary Multiple Solitary Solitary Three lesions solitary Number of lesions Surgery – – – – – – – – Surgery Surgery Surgery Surgery Procedure Under follow-up – – – – – – – – Death/20 days Death/1 year Death/2 years & 9 months – Outcome/ follow-up duration Histopathology Death/few days – – – – – – – Histopathology Histopathology Histopathology Histopathology Confirm after Adenocarcinoma, probably from colon origin – – – – – – – – Calcified metastasis of osteosarcoma Squamous cell carcinoma of the lung Metastatic adenocarcinoma Non-small cell carcinoma of lung Histopathology 4 The Neuroradiology Journal 0(00) Bahrami et al. Hounsfield units on CT scan (60 Hounsfield units) and MRI findings, the first diagnosis was a metastatic calcified mass confirmed intraoperatively. Considering the intraoperative observation, intraparenchymal meningioma was the most important differential diagnosis (due to shape, consistency and calcification of tumour). Ultimately, histopathological examination confirmed the diagnosis of metastatic adenocarcinoma. A thorough follow-up demonstrated that the caecum of the large intestine was the origin site of the tumour without additional dissemination of the primary lesion except for brain involvement. A retrograde history demonstrated that the patient had no gastrointestinal symptoms, and the brain lesion-related symptoms were the presenting symptoms of her cancer. After a 4-month follow-up, the patient was neurologically stable with no brain recurrence, while she was undergoing systemic chemotherapy. 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