Atypical Clinical and Radiologic Findings in a Patient with Brain Metastatic Lesions

Atypical clinical and radiologic findings in a patient with brain metastatic lesions


INTRODUCTION
The most common neoplasms in the adult brain are brain metastases, which can be up to 10 times more frequent than primary brain tumors. [1]It is estimated that 20% of cancer patients develop brain metastases in the course of their disease.According to the guidelines for diagnosis, follow-up, and treatment of most solid tumors, routine magnetic resonance imaging (MRI) of the brain is not recommended, except for the emergence of new-onset neurologic symptoms.Supposedly, this implies even more incidence of occult brain neoplastic involvement, which is confirmed by autopsy reports of deaths due to neoplastic disorders.4] Brain metastases could frequently be the cause of the first presenting symptoms in patients with still undiagnosed, but already advanced primary tumor [5] , as is the example with our patient.

CASE REPORT
A 47-year-old male presented to our clinic with a 1-month history of constant headaches, primarily in his left temporal area, accompanied by nausea and occasional vomiting.
On this background, he reported episodes of intense, sharp, 'shooting' pain with the same localization radiating to the face.The patient claimed his voice had changed, he had developed vertigo, and he had had an unsteady gait for the last month.For 2-3 weeks, he noticed a swelling under his lower jaw on the right.After seeing a private practice neurologist, the patient was given several nutraceuticals in addition to pregabalin 75 mg daily.He claimed to have had no prior medical history or contact with animals.He has been employed by a peat processing plant in Sweden.Admits to smoking cigarettes.

Physical and neurologic examinations
A palpable, painless, and mobile formation with a soft-elastic consistency was found in the right submandibular region, which we assumed to be packed enlarged lymph nodes.
The neurologic examination confirmed: 1. Syndrome of intracranial hypertension -headache, nausea, and vomiting, without visual disturbances.2. Discoordination syndrome -static ataxia (positive Romberg sign with instability to either side), locomotor and dynamic ataxia with an intentional tremor in finger to nose and heel to shin tests bilaterally, with no asymmetry, as well as horizontal nystagmus in lateral gaze, especially when looking to the right.3. Bulbar syndrome -dysphonia.4. Cephalgic syndrome -paroxysmal 'shooting' pain in the region of innervation of V1 and V2 branches of the trigeminal nerve.

Laboratory investigations
Hematologic tests and biochemical analyses of the patient did not reveal any notable deviations.Following a lumbar puncture, CSF samples were taken for cytology, biochemistry, and microbiology examination.The microbiological samples remained sterile, while the biochemical results were unspecific -a double increase of IgG and a slight hyperproteinorachia.Additionally, serologic tests for toxoplasmosis, echinococcosis, toxocariasis, and cysticercosis via the ELISA method were negative, as were the stool cultures for amebiasis, VDRL for syphilis, and HIV-ELISA.

Neuroradiology
An MRI of the brain registered numerous (over 20) supraand infratentorial lesions, heterogeneous in their shape and size -primarily oval, some of them grape-like, with a solid capsule and a non-homogenous intralesional structure, presenting isointense as the brain parenchyma in T2 sequence and hypointense in T1, as well as discreet perifocal vasogenic edema (Figs 1, 2).After contrast agent administration, a peripheral, 'ring enhancement' (Fig. 2) of lesions was documented, while new punctiform and lacunar lesions were visualized.The vermis, the left cerebellar hemisphere, the frontoparietal subcortical white matter bilaterally, the right thalamus, and the occipital cortex bilaterally were all particularly marked.The imaging department concluded that those findings correlated mostly with 1. neurocysticercosis in predominantly colloidal phase, 2. tuberculomas, and 3. hematogenous spread of an occult neoplasm.

Further diagnostic evaluation of the etiology of lesions
A chest X-ray was performed and was described as lacking significant signs of pulmonary disease.An abdominal ultrasound showed evidence of hepatic steatosis without focal lesions.An ultrasound of the cervical region confirmed submandibular lymphadenopathy on the right.Electroencephalography registered non-specific slow-wave abnormalities in the left parietal area.An ear, nose, and throat specialist documented paresis of the left true vocal cord via indirect laryngoscopy.A CT scan of the cervical region documented degenerative changes and intervertebral disc protrusions at levels C3/C4 and C4/C5, which did not correlate clinically with our patient's history and physical examination.
The patient was then referred for surgical exploration of submandibular lymphadenopathy.The excised material was sent for histological analysis, which documented that all lymph nodes in the sent material had been engaged by a poorly-differentiated adenocarcinoma.According to the conclusion of the pathologist, the immunohistochemical constellation of СК7 (+/−), CK20 (−) neg., p63 (−) neg., TTF-1 (−) neg., PSA (−) neg., and CD56 (−) neg.excluded the possibility of the primary tumor being located in the lungs or the prostate, and assumed the possibility of it being in the breast.
Due to the unresolved diagnostic queries, a decision was made to perform a whole-body PET/CT scan, which visualized a spiculated lesion in the 10th left lung segment, engaging the pleura, extending to the left hilum, and converging with a pack of mediastinal lymph nodes.The whole formation had the dimensions of 5.3×5.3cm and demonstrated increased metabolic activity with a SUVmax -12.38 (Fig. 3).Single paratracheal and hilar lymph nodes also showed evidence of a higher metabolic rate with a SUVmax -12.84.Another metabolically active lesion, 0.7 cm in diameter, was found in the mesentery next to the descending colon, and one more, 1.7 cm in diameter, on the midline of the pelvic inlet.

Therapy
Treatment with mannitol and dexamethasone was administered as anti-edema measures, combined with analgesic therapy with pregabalin and tramadol, which alleviated the patient's subjective symptoms.
Following multiple consultations with a pulmonologist, thoracic surgeon, and neurosurgeon, the patient was deemed inoperable and was referred for chemotherapy and palliative CNS irradiation.

DISCUSSION
The present case report provokes interest because of the clinical and radiological heterogeneity of the brain metastatic lesions that have become a diagnostic challenge for a great number of medical specialists.The first clinical symptoms of the advanced malignant process are associated with brain metastases, coupled with the conflicting evidence provided by the laboratory and radiological investigations, which could direct the clinician's thinking in the wrong direction.
The relevant scientific literature contains cases of similar diagnostic conundrums.A case report published in the British Medical Journal by Barbone et al. [6] described a 50-year-old female patient with numerous supra-and infratentorial circular cystic lesions found on CT and MRI of the brain due to symptoms of vertigo and upper extremity weakness.The CT lesions were hypodense, partially calcified, while the T2-sequence of MRI demonstrated a characteristic for neurocysticercosis, the 'hole in the dot' feature, which after contrast agent administration acquired a peripheral, 'ring-enhancing' contrast pattern.The final diagnosis is reached after a whole-body CT scan registered a proliferative process in the upper right pulmonary lobe.
A clinical case from the International Journal of Clinical Oncology describes a 47-year-old male with bilateral neurosensory hearing loss, tinnitus, and a discoordination syndrome.The CT and MRI of the brain demonstrated multiple supra-and infratentorial well-defined oval cystic lesions, without evidence of vasogenic edema and no contrast enhancement.At first, the lesions are assumed to represent the vesicular phase of neurocysticercosis, but later, a CT of the thorax, as well as bronchoalveolar lavage cytology, and a transbronchial biopsy confirm a pulmonary adenocarcinoma with brain metastases. [7]nother case from the British Medical Journal presents a 41-year-old female with focal motor seizures with secondary generalization.CT and MRI of the brain reveal over 10 cystic formations with discreet peripheral contrast enhancement, with a solid and liquid component found in some of them, without evidence of vasogenic edema and mass effect.The engagement of the subependymal space of the lateral ventricle, the presence of multiple cystic lesions with calcifications, coupled with the absence of brain edema lead the medical team to neurocysticercosis as the most probable diagnosis.However, subsequent CT of the thorax and video-assisted thoracoscopic surgery found multiple pulmonary nodules, histologically verified as squamous-cell metastases from primary cervical cancer. [8]ess than 10% of patients manage to survive 2 years after diagnosis, indicating that the lethality of brain metastases remains high despite advancements in neoplastic disease therapy. [9]Despite this, the average survival time for patients with brain metastases from breast cancer and pulmonary adenocarcinoma has increased recently and is now 15 to 16 months. [10]ith the present case report, we would like to highlight the challenges that face the clinicians in the process of diagnosing malignant neoplasms despite the access to contemporary laboratory and imaging facilities and even in cases of already advanced disease.The timely diagnosis remains of utmost importance for successful treatment and improved prognosis of cancer patients.

Figure 1 .
Figure 1.A solid lesion in the cerebellar vermis leading to the fourth ventricle compression.

Figure 2 .
Figure 2. A circular lesion in close proximity to the right lateral ventricle with peripheral ring-enhancing characteristic after contrast agent administration.

Figure 3 .
Figure 3.A spiculated lesion in the left lung, engaging the pleura, extending to the left hilum and converging with a pack of mediastinal lymph nodes.