Advanced prostate cancer with brain metastasis presenting with isolated severe headache without urinary symptoms.

Abstract

Introduction and clinical importance

Brain metastases from prostate cancer are uncommon, occurring in fewer than 1 % of cases of metastatic prostate cancer. Brain metastasis can cause cerebral edema, neurologic symptoms, and may be misdiagnosed as primary brain tumors on imaging if thorough investigations are not done. It is difficult to identify and diagnose brain metastasis from prostate cancer since the intracranial metastatic process and presentation are poorly understood and limited to case studies. Most patients with brain metastases from prostate cancer exhibit a variety of metastatic symptoms; however, this patient's presentation was defined by only isolated intense headache. Our goal is to draw attention to the uncommon instance of brain metastases from prostate cancer in addition to reviewing the literature on the advances in treatment for prostatic cancer with metastasis to the brain.

Case presentation

We report the case of a 67-year-old male with metastatic prostate adenocarcinoma into the brain, presenting with isolated severe headache with no prostate cancer symptoms. Following extensive radiologic examination, metastatic deposits were detected in the left side of the brain with multiple intracerebral and cerebellar vermis lesions. Multiplanar T2 weighted abdominal pelvic MRI visualized the primary lesion in the prostate which was confirmed by histology. After a month following surgical castration, the patient reported resolved headache and resumed his daily activities. The patient's serum PSA decreased from 7.8 ng/ml to 0.3 ng/ml during a 12-months follow-up with no neurological symptoms.

Clinical discussion

Prostate cancer rarely causes brain metastases, and the percentage of all brain metastases that originate from prostate cancer is seldom updated. It can be difficult to distinguish between primary brain lesions and metastatic brain prostate cancer, particularly when there is just one lesion present. Despite the recently developed diagnostic approaches, symptomatic patients exhibit a variety of clinical manifestations that vary depending on the location of the metastatic focus. These manifestations include headache, seizures, and focal neurological deficits, in addition to some common non-focal manifestations like confusion and memory deficits. Our patient had a PSA of 7.8 ng/ml at the beginning and the DRE results were normal, clinically prostate cancer was not thought to be the main cause of brain metastasis. Abdominal pelvic MRI was performed to investigate the primary lesion and confirmed the presence of prostate cancer with extra prostatic extensions. Adenocarcinoma prostate cancer was found to be the main cause when histopathology was done.

Conclusion

This report reviews the literature on brain metastases from prostate cancer and points out that while very rare, brain metastases from prostatic cancer do occur and should not be overlooked, particularly in light of the recent advancements in prostatic cancer therapies that may extend the patient's survival. Gadolinium-enhanced MRI is necessary to confirm or rule out brain metastases if it is suspected, as well as to monitor prostate cancer patients.

Highlights

• •Brain metastases from prostate cancer are uncommon.
• •It is difficult to identify and diagnose brain metastasis from prostate cancer.
• •Most patients with brain metastases from prostate cancer exhibit a variety of metastatic symptoms.
• •Gadolinium-enhanced MRI is necessary to confirm or rule out brain metastases if it is suspected.
• •Treatment of prostate brain metastasis depends on the patient clinical presentations.

1. Introduction and clinical importance

One of the most prevalent cancers in males worldwide is prostate cancer, which typically spreads to the liver, lungs, and bones [1]. Prostate cancer brain metastases are uncommon and are typically found in post-mortem examination. Usually, these metastases are limited to individuals with extensive metastatic diseases. It is much less common for metastatic prostate cancer to solely spread to the brain [2]. Most of the time the clinical presentation of prostate cancer brain metastasis is asymptomatic or coupled with headache, dizziness, behavioral changes, and memory loss [3]. However, brain metastasis from prostatic cancer (PC), especially prostate adenocarcinomas is very rare, in contrast to lung, breast, melanoma, colon, and kidney malignancies, which are more commonly associated with brain metastasis [4]. It only occurs in 0.04 % to 2 % of cases of prostate adenocarcinoma [5,6]. Previously, it was long believed that the brain parenchyma could resist the growth of metastatic tumor from prostate cancer cells [5].

Considering that the majority of patients with prostate cancer who develop brain metastases may or may not exhibit urinary tract symptoms at first, these lesions are often ignored in clinical practice or may be mistakenly identified on a routine CT head scan for meningiomas, abscesses, or subdural hematomas [4]. As a result, brain metastases in Prostate Cancer patients are typically discovered as postmortem findings, and the only information available in the literature about their clinical presentation is limited to case reports. In these situations, the prognosis is dismal and the median overall survival varies from one to two years contingent upon the treatment plan used [3].

Surgery, radiation, or chemotherapy may be treatment options, depending on the patient's performance status, involvement of systemic disease, and presentation. Here, we describe one specific case of a patient with prostate adenocarcinoma who did not exhibit any typical urinary tract symptoms of prostate cancer but instead solely experienced an intense headache. The initial brain MRI revealed secondary lesions, and several investigations were carried out to determine the underlying cause.

2. Case presentation

We report the case of a 67-year-old man who had a severe headache for three months. The headache started suddenly it was generalized throbbing in nature associated with intermittent dizziness with no signs of increased intracranial pressure; however, it was slightly eased by anti-pain medication. The patient stated that before the headache, he had been experiencing eye pain which led him to visit multiple eye clinics, but his condition did not get improved. After that, he was referred to a neurosurgeon, who discovered a secondary metastatic lesion in his brain by using MRI (Fig. 1A & B). Many investigations were made in an attempt to find what was the primary lesion.

Fig. 1.

T1-weighted pre- and post‑gadolinium contrast MRI of the brain. A & C are weighted pre‑gadolinium and B&D are post‑gadolinium contrast MRI of the brain showing multiple enhancing lesions seen in the left basal ganglia, left occipital (short arrows on image 1B) and cerebellar vermis (short arrow on image D). The largest is in the left basal ganglia and cerebellar vermis measuring 1.7 × 1.5 cm and 1.8 × 1.52 cm in size respectively.

Patient had no history of Lower urinary tracts symptoms, hematuria, lower limbs edema, or history of lower back or bone pain symptoms, he also denied history of palpitations or diaphoresis, neither history of cough, difficulty in breathing or chest pain. On general examination he was conscious, not pale, not jaundiced. The abdominal examination revealed normal findings. The digital rectal examination revealed a soft prostate grade II, a median sulcus that was not obliterated, and free rectal wall mucosa.

The alpha fetal proteins, C-125, Ca19-9, and carcinoembryonic antigen (CEA) were all normal. The results of the complete blood counts, liver enzyme tests, electrolytes, lipid profile, renal function tests, and HBA1C were all within normal limits. Metastatic workup such as Chest X-ray and chest CT were unremarkable. Sputum for culture and sensitivity revealed normal flora isolation. Gene X-pert sputum tests revealed no mycobacterial TB. The results of the bronchoscopy were normal, the cytology of the bronchial fluid revealed persistent non-specific inflammation, and the 48-hour analysis of the pulmonary fluid showed no growth or lung lesions. The Lung didn't seem to be the primary source of the brain tumor (Fig. 2).

Fig. 2.

Normal CT of the chest performed with intravenous contrast during arterial phase with no evidence of primary tumor lesions.

An MRI of the brain revealed multiple intracerebral and cerebellar vermis lesions with surrounding oedema. The greatest lesions, measuring 1.7 × 1.5 cm and 1.8 × 1.52 cm respectively were seen in the cerebellar vermis and left basal ganglia (Fig. 1 A & B). KUB ultrasound revealed no signs of bladder outlet obstruction and an enlarged prostate measuring 40.2 cm. PSA results was 7.8 ng/dl.

MRI of the abdominal pelvic revealed Prostate Cancer with extracapsular extension invading the bilateral seminal vesicles with Multiple metastatic regional and inguinal lymph nodes recommending doing histology for primary cause confirmation (Fig. 3A/B/C). TNM staging showed extra-prostatic extension bilaterally, metastatic inguinal lymph nodes brain mets with stage T3aN1M1 and diagnosis of advanced prostate cancer with metastases to the brain was made. Thus, the patient was planned for core prostate biopsy which revealed adenocarcinoma of the prostate with Gleason score 4 + 4 = 8, ISUP grade 4 (Fig. 4A & B).

Fig. 3.

A. T2 weighted abdominal pelvic MRI. Green arrow shows prostate gland appears abnormal in size displaying abnormal signal intensity non-circumscribed, homogeneous, significantly hypointense, and >1.5 cm in greatest dimension on the right peripheral zone. It has definite extra-prostatic extension and bilateral seminal vesicles invasion which is seen in white arrow.

B. DWI MRI. Arrows shows restrictions of the bilateral seminal vesicles in keeping with invasions.

C. Prostate MRI on Diffuse Weighted Image (DWI). Two white arrows show metastatic regional and inguinal lymph nodes. Green Arrows shows restricted diffusion with high cellular Lesions. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 4.

A. H&E Photomicrograph (×100). Tissue core biopsy shows micro glands and tumor invading the fibromuscular stroma in a solid growth pattern, individual cells and poorly formed glands.

B. H&E Photomicrograph (×400). Tissue core biopsy shows micro glands that are back-to-back forming cribriform pattern and loss of myoepithelial layers with nodular proliferation of atypical glands which were small single layered without myoepithelial cells and were closely packed.

MRI of the total spine showed marginal osteophytes of the thoracis vertebral bodies and cervical disc osteophytes which was seen at C3 to C6 with indentation of anterior thecal sac and spondylodiscopathy (Fig. 5A & B). The patient was informed about the possible therapies based on his performance status, and he ultimately chose androgen deprivation therapy (ADT). Following bilateral orchidectomy, his serum PSA decreased to 0.3 ng/ml from 7.8 ng/dl. A month later, the patient's headache had completely disappeared. The patient was planned for chemotherapy and craniotomy with tumor resection If his symptoms had not been improved. During a 12-months follow-up, he reported no headache, or neurological symptoms and PSA was undetectable. He resumed his normal daily activities.

Fig. 5.

A & B: Lumbosacral MRI. The total MRI spine revealed (cervical and thoracic not in the image) degenerative changes in keeping with Spondylodiscopathy with no evidence of metastasis to the spine.

3. Clinical discussion

Prostate cancer seldom causes brain metastases, and the percentage of all brain metastases that originate from prostate cancer is rarely updated. Prostate and neuroendocrine cancer patients are more likely to have brain metastases than lung or melanoma cancer individuals [7]. Similar to other solid tumors, prostate cancer (PC) is a heterogeneous mass of cells with various molecular patterns and changes in genetic mutations [1]. The diverse behaviors that PC exhibits in relation to brain metastases may be explained by this heterogeneity. Since PC metastasis usually spreads via lymphatic or blood vessels, primary tumor cells of PC could directly apply to the brain microenvironment via several mechanisms [4]. A tumor embolism may avoid the lung by passing through a patent foramen ovale. Otherwise, the tumor's primary cells possibly could gain the lung capillaries, pass through the left heart, and consequently spread via arterial blood [4].

Additionally, some research has suggested that secondary spreading of PC cells from a preceding metastatic niche, like the liver or the lung, could spread into the brain [4]. Brain metastasis may also occur as a late occurrence as a result of weakened immune system or a breakdown in the blood-brain barrier [8]. It can be difficult to distinguish between primary brain lesions and metastatic prostate cancer, particularly when there is just one lesion. Although specific MRI features associated with metastatic prostate cancer have not been thoroughly documented in the literature, several studies include mixed cystic, solid, or ring-like MRI appearances as well as hemorrhagic brain metastases [9]. It may be difficult to diagnose brain metastases in PC patients unless they have neurological symptoms [4]. In spite of recently developed diagnostic techniques, such as integrated positron emission tomography (PET)/magnetic resonance imaging (MRI) scanners using the prostate-specific membrane antigen (PSMA) with 18F- and 68Ga-labeled PET agents, symptomatic patients exhibit clinical manifestations that vary depending on the site of the metastatic focus, including headache, seizures, and focal neurological deficits, in addition to some frequent non-focal manifestations like confusion and memory deficits [4].

Initial PSA value for our patient was 7.8 ng/ml, which did not support the diagnosis of prostate cancer as the primary cause. However, a Multiplanar abdominal pelvic MRI suggested that the underlying lesion may have been prostate cancer, and histology confirmed this hypothesis (Fig. 4). Prostate cancer in this patient was diagnosed at a late stage when it had spread far and was not generating neurological symptoms or symptoms related to the lower urinary tract which are common in cases of metastatic prostate cancer. When a patient has metastatic brain prostatic disease, brain biopsy is not advised. Histopathology of the primary is the preferred confirming test; however, in patients with poor prognosis, it is not necessary.

According to historical reports, radiation therapy possibly including whole brain radiation therapy (WBRT)—followed by craniotomy with resection has been used to treat solitary brain metastases [2]. Androgen deprivation therapy was initiated for our patient with close monitoring for any neurological symptoms, apparently no neurological symptoms appeared in a follow up of 12 months. Control MRI of the brain was planned after 6 months but due to financial constraints the patient couldn't accomplish.

4. Conclusion

Metastatic prostate cancer presenting with isolated intense headaches due to metastasis to the brain is a rare finding that can occur at relatively low PSA levels. Diagnosis of prostate cancer must be considered even in cases where imaging or histopathology do not indicate metastatic disease in men who meet the right demographics and have abnormal digital rectal exams. Gadolinium-enhanced magnetic resonance imaging is necessary to confirm or rule out brain metastases if it is suspected, as well as to monitor PC patients. The recommended treatment for brain metastatic prostate cancer is Tumor resection in combination with ADT and chemotherapy, however our patient symptoms resolved only by ADT with no neurological symptoms afterwards. In addition, there should be more research and publications on PC brain metastasis because it offers a critical chance to comprehend the metastatic brain process better.

Disclosure

This report has been published in accord with SCARE criteria [10].

Informed consent and consent for publication

Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Ethical approval

This case report study was exempt from ethical approval at our institution, as this paper reports a single case that emerged during normal surgical practice.

Funding

There was no funding concerning this article.

Author contribution

Dr. Charles Nhungo: Pathological and radiological images search, literature review, writing the paper, final manuscript arrangement and patient follow up.

Dr. Daniel Kitua: General manuscript corrections.

Dr. Boniface Nzowa: Case report concept.

Dr. Mukama Kasori: Case report concept.

Dr. Victor Sensa: Supervisor.

Prof Charles Mkony: Correction and elaboration of the final manuscript.

Conflict of interest statement

The authors declare that they have no competing interests.

Data availability

This is not applicable to this article because this is a case report.