Epidemiological, Clinical, Diagnostical and Histopathological Aspects of Medular Compressions of Metastatic Origin

Background: according to the World Health Organization (WHO) in 2019, cancer metastasis constitutes a fast proliferation of abnormal cells which spread to other organs. Bone is the third most targeted organ behind the lungs and the liver, and the most frequent bone’s localizations are; the spine, pelvic bone and the ribs. Metastatic spinal compressions constitutes, a well-defined clinical entity of which the prevalence and incidence depends on the primitive tumor, Objective: To study the epidemiological, clinical, diagnosis and the histopathologic aspect of spinal cord metastatic compressions. Patients and method: It was a retrospective descriptive study over a period 10 years in the Douala General and Laquintinie Hospitals. We included in our study patients with slow spinal compression since January 1st 2010 to December 31st 2019. We included in our study, filled patients medical reports suffering of a primitive tumor which spread to the spine, with pathological and radiological evidence. Results: we recruited a total of 125 patients of which 68% where male and 32% female with a sex-ratio of 2.12, the mean age was 55.8 ± 15.397. The most frequent spine localization of metastasis was the lumbar region 57.1%. The spine pain was the main symptom seen in 98.4% associated to radicular nerf pain in 33.6%, sensibility and motor dysfunctions represented 94% and 92% respectively, and urinary dysfunction represented 44.8%. The diagnosis was essentially based on spine X-rays and was being realized in 64.8% of cases. Lytic lesions and bone condensation were the main abnormalities viewed with 22.4%. The second group of imaging was the CT-Scan and MRI done in 62.4%. The most represented primitive tumor was the prostate cancer 59 cases (47.25%) with adenocarcinoma as the main histological type 56 cases. Breast cancer came next with 32 cases (25.6%), invasive ductal carcinoma as the most represented histological type 26 cases (20.6%). The lung cancer came at the third position with 7 cases (10.4%) with the small cell carcinoma been the most represented histological type with 4.8%. Conclusion: spinal cord compression of metastatic origin is a frequent pathology in patients with osteophilic tumor, despite adequate measures, the prognosis remains unresolved. Emphasis should be placed on raising awareness of different early diagnostic measures.


Introduction
According to the World Health Organization (WHO) 2019, metastases are the detachment of cancer cells from a primary tumor that will swarm to another part of the body using lymphatic vessels or blood vessels [1]. Its locations are multiple and can occur on several organs. Bone is the third most affected organ after the lung and liver [2]. The most frequent bony locations are: the spine, pelvis and ribs [2]. Spinal cord compression is any injury starting from the spinal or intraspinal cord compressing the spinal cord and gradually leading to loss of function [3].
Metastatic lesions of the spine are a very disabling entity, on the one hand because of the pain they induce and on the other hand because of the neurological deficit [4]. Worldwide, the incidence of metastases varies depending on the location of the primary cancer [5]. A study conducted in the United States by Domchek et al showed a rate of metastasis in the spine of 19.6% of the various primary cancers distributed as follows: breast cancer 8.4% myeloma 3.6% cancer of the prostate 2.4% and other 5.2% (lung cancer, kidney cancer, cervical cancer, etc.) [6].]. The work done in Morocco by R. Karim et al showed that the average age of onset of spinal metastases was 46 years with a predominance of men; the primary tumor was bronchogenic cancer in men and breast carcinoma in women [7]. Clinically radicular pain is found at 94%, lumbar instability at 10%, numbness at 79%, retention problems and urinary incontinence at 61% [8]. Paraclinical diagnosis is currently facilitated by standard radiography and CT scan of the spine which could objectify bone lysis. Medullary MRI shows the impact on the marrow [9]. The definitive diagnosis is obtained by surgical biopsy after laminectomy or a fine needle aspiration [10]. According to the French Neurosurgery Society, the main treatment for spinal metastases is surgery. Radiotherapy and postoperative chemotherapy are used respectively if the primary tumor is radioactive and chemosensitive [11]. Spinal cord compression of metastatic origin is an oncological and neurosurgical emergency and is a common complication of cancer. Survival after the onset of malignant spinal metastases is reduced with the onset of motor and sensory neurological deficits, spinal cord ischemia with edema [4]. The scarcity of studies in Africa in general and in Cameroon in particular aroused our interest in this study with the aim of contributing to the management of spinal cord compression of metastatic origin in Cameroon.

Material and Methods
It was a descriptive study with retrospective data collection, carried out in the departments of surgery, oncology, neurology, anatomo-pathology, radiology, radiotherapy of the General and Laquintinie hospitals in Douala, over a period of 10 years (January 2010 -December 2019). We went to the archives of the centers where the patient files were stored. We selected the files of patients with slow spinal cord compression, from which we selected the charts of patients with metastatic spinal cord compression with pathological and radiological evidence. The variables collected were: age, sex, history (diabetes, hypertension, cancer and other chronic pathologies), characteristics of pain, motor deficits, sensory deficits, sphincter disorders, results of laboratory tests and radiological, histological types of primary tumors. The data collected were recorded and analyzed by the computer statistical software Epi Info version 3.5.4.

Age
As shown in figure 1, the age of the population varied between 12 and 84 years with an average of 55.8 ± 15.397 years. The most represented age group in our series was between 62-72 years 36 cases (28.8%).

Sex
A total of 85 (68.0%) were male and 40 (32.0%) were female, for an M / F sex ratio of 2.12.

History (Known Tumor Pathology)
The most represented cancer was that of the prostate 24 cases (19.2%) with adenocarcinoma as histological type, followed by breast cancer 12 cases (9.6%) with ductal carcinoma as histological type. (Table1).

Evolution Period
In our study, 12 cases had an evolution period of less than one month (time between the discovery of cancer and the appearance of spinal metastasis), 23 cases (57.5%) 1 to 6 months, 20 cases between 6 and 12 months and 10 patients an evolution period beyond 12 months.

Data from Standard Radiography, CT Scan and MRI
of the Spine As shown in table 4, radiography was performed in 81 cases (64.8%); the images showed that lytic lesions were represented in 28 cases (22.4%) located mainly on the lumbar vertebrae in 15 cases (12%), followed by osteocondensation lesions 28 cases (22.4%) predominant on the lumbar vertebrae 18 cases (14.4%).
CT and MRI were performed in 115 cases (92%) and the radiological image the most found was bone lysis in 44 cases (32%) with localization in the lumbar spine 26 cases (20.8%)

Bone Scintigraphy
In our series, bone scintigraphy was found in 18 files (14.4%); the lesion found was localized hyperfixation in the lumbar spine in 13 cases (10.4%) followed by the dorsal spine in 4 cases (3.2%).

Certainty Diagnosis
We found 125 files (100%) in which the patients had performed a post-laminectomy biopsy.

Histological Types (Primary Cancers)
The most common primary cancer was prostate cancer in 54 cases (43.2%) with adenocarcinoma as the most common histological type in 52 cases (41.6%), which had the lumbar spine as the site of preferential metastasis in 41 cases of metastases (26.65%). Breast cancer was the second most common primary tumor in 29 cases (23.2%); ductal carcinoma was its main histological type in 24 cases (19.2%) and lumbar spine in 18 cases (17.6%) its preferred site of metastasis (table 8).

Discussion
The mean age of the population was 55.  [12][13][14]. This can be explained by the fact that cancers grow in an insidious way.  [12,14,15]. This may be partly explained by the prevalence of prostate and lung cancer in men.
Spinal pain reflects the suffering of the osteo-discoligamentous elements of the spinal canal, segmental stiffness of the spine easier to demonstrate in the cervical and lumbar areas which are normally more mobile than the dorsal region and pain caused by the pressure of the processes in spinous and paravertebral muscles. These signs constitute the spinal syndrome which is more frequent in lesions of the spine but which may accompany a juxta or even intramedullary tumor. In our series spinal pain was presented in 123 cases (98.4%) with lumbar pain in 89 cases (66.4%) chest pain in 38 cases  [15][16][17]. This can be explained by the fact that back pain is one of the telltale signs of spinal cord compressions.
Radicular pain is fixed, tenacious and unilateral at the beginning of metameric radicular topography, of variable intensity, often nocturnal or with nocturnal recrudescence. The radicular syndrome will be clearer in the cervical region where the radicular territory is well individualized and better explored, whereas in the thoracic region it can be reduced clinically to intercostal pain in the hemi-girdle [18]. Radicular pain was represented in 42 cases (33.6%) with sciatica in 30 cases (73%) cervico-brachial neuralgia in 5 cases (12%) cruralgia in 5 cases (12%) and intercostal neuralgia in 2 cases (1.6%). These results are similar to those of Younes et al in Morocco in 2016 and Alkadi et al in Algeria in 2017 who found respectively that radicular pain was represented in 32% and 30% broken down respectively as follows: sciatica in 66.7% and 66.6% cervicobrachial neuralgia in 18.3% and 16.66 cruralgia in 8.3% and 16.66% intercostal neuralgia in 6.7% and 0% [17,19]. This pain is often poorly described and reflects the suffering of the directly compressed metamer and is therefore capital because it readily allows locate the level to be explored radiologically.
Often delayed in relation to motor signs, are of great importance for the diagnosis of spinal cord compressions. In our series, sensory disorders were represented in 117 cases (93.6%), more marked by paresthesia in 61 cases (53.0%), numbness in 38 cases (33.0%) and anesthesia in 18 cases (15.7%). These results are not similar to those of Djiencheu in Yaounde (Cameroon) in 2007 and Kone et al in Mali, who found sensory disorders respectively in 59.7% and 56.6% of cases [14,15]; this can be explained by the fact that the patients recruited had already undergone slow spinal compressions. Moreover, Diomande et al in Côte d'Ivoire in 2015 on slow spinal cord compressions found similar results with sensory disorders reported in 78.5% of cases [20]. These disorders are essentially subjective; data from the literature show that these signs are reported in 20.5 to 50%.
Motor disorders were represented in 92% of cases marked by paraparesis 61 cases (48.8%), paraplegia 48 cases (38.4%) and quadriplegia 6 cases (4.8%). Several studies had found similar results, in particular Djiencheu et al in Cameroon in 2007 who found motor disorders in 89.6%, marked by paraparesis in 60% of cases, paraplegia in 31.7% of cases, tetraparesis in 6.7% of cases and quadriplegia in 1.7% of cases. Diomandé et al at the CHU de Cocody in Abidjan in 2015 on slow spinal cord compressions found motor disorders at 98.3% [14,20]. Younes et al in Morocco in 2016 on the management of spinal cord compressions of tumor origin found that motor disorders were present at 92% [17]. They determine the urgency of the treatment because they mark the degree of compression of the spinal cord and they represent one of the first causes of consultation in neurosurgery in the event of spinal cord compression.
Sphincter disorders were represented in 56 cases (44.8%), more marked by urinary incontinence in 51 cases (40.8%) and retention disorders in 5 cases (4.0%). Studies carried out by Djiencheu et al in Cameroon in 2007 and Diomande in Côte d'Ivoire in 2015 found similar results with respective sphincter disorders of 53% and 40.5% [14,20]. In 2013, a study conducted by Kassegne et al in Togo on slow spinal cord compressions found sphincter disorders in 67% [21]; this difference can be explained by the fact that the patients presented to the hospital in advanced stages of their pathologies. Relatively late sphincter disorders are limited for a long time to delayed urination, urgent and frequent urges to urinate and later retention with incontinence [22].
While plain front and lateral radiographs of the spine are still performed as a clearing up examination for spinal pain syndrome, this examination very often remains negative at the onset of a bone tumor, benign or malignant. It is in fact known that a reduction of at least 50% of the calcium load within a bone tissue is necessary for there to be a translation on conventional radiography. In our series, radiology was performed in 64.8% of cases, the images showed that lytic lesions were represented in 28 cases (22.4%), osteocondensation lesions in 28 cases (22.4%), vertebral compression in 20 cases (16.0%) and mixed lesions in 5 cases (4.0%). These results are similar to those of Younes et al in Morocco in 2016 on the management of tumor spinal cord compressions in which the radiology was performed at 87% with osteolytic images at 22%, vertebral compression at 15.8% and osteocondensation at 6% [17]. A study conducted by Alkadi et al in Algeria in 2017 on vertebral metastases found discordant results with a completion rate of 40%; the most prominent pathological aspect was 50% vertebral compression followed by 40% bone lysis [19]. This can be explained by the fact that the x-ray, not being a standard examination for the diagnosis of spinal compressions, was less performed.
CT and MRI of the spine were performed in 115 cases (92%), with bone lysis in 44 cases (32%), compression in 39 cases (31.2%) and vertebral compression in radiological images. 29 cases (23.2%); the site of the lesion was found in 100% of cases. These results are in disagreement with those of Djiencheu et al in 2007 in Yaounde (Cameroon) on slow spinal cord compressions of tumor and pseudotumoral origin in which the diagnostic exploration of choice was the myeloscanner 47.8% [14]. This could be explained by the unavailability of MRI. These results are similar to those of Younes et al in Morocco who found the site of compression in 100% of patients with osteolysis followed by an intracanal process as the main radiological image [17]. This can be explained by the fact that these examinations are standard for the diagnosis of spinal cord compression and always confirm the lesion topography In our series, the most represented vertebral metastasis location was lumbar with 88 cases (57.1%), followed by thoracic location in 58 cases (37.7%) and cervical location in 8 cases (5.2%). On the other hand, studies carried out in Cameroon (Yaounde) in 2007 by Djiencheu et al and in Morocco in 2016 by Younes et al found a rate of dorsal metastases at 55% and 52%, lumbar 30%, cervical 15% [14,17]; this can be explained by the fact that their samples were smaller than ours. These results are similar with a study conducted by Alkadi et al in Algeria in 2017 on vertebral metastases, finding a rate of lumbar metastases of 50% and a rate of thoracic metastases of 40% [19]. This can be explained by the fact that the spine is a highly vascularized region rich in growth factor.
The chest x-ray has an important place in tumor pathology because it is necessary as part of an extension workup which is often for diagnostic purposes since the lung is the first target organ for metastasis. This examination is also performed in the pre-radiotherapy assessment. The chest xray was normal in 7 cases (5.6%) and abnormal in 21 cases (16.8%) and opacities were found in 6 cases (4.8%), pleural effusions in 6 cases (4, 8%), micronodules in 5 cases (4.0%), balloon release (0.8%), non-quantifiable enlargement (0.8%), atelectasis band (0.8%), posterior arch lysis (0.8%). These results are similar to those of Younes et al in Morocco in 2016 and Alkadi et al in Algeria in 2017 who found respectively similar results with abnormal radiological image in 29 cases (15.4%) and 18 cases (20%) [17,19]. This can be explained by the fact that the chest x-ray is often replaced by the thoraco-abdomino-pelvic scanner.
Abdominal ultrasound has a key place in cancer disease with several advantages because it is inexpensive and accessible; it makes it possible to make the diagnosis of digestive metastases in occurrence hepatic metastases and peritoneal carcinomas. This examination is also used in the pre-radiotherapy assessment. In our series we had a completion rate of 94.4% with 11.2% of images which were pathological, namely 7 cases (5.6%) of homogeneous hepatomegalies, 3 cases (2.4%) of secondary hepatic locations, 2 cases (1.6%) of splenomegaly, 2 cases (1.6%) of lymph node involvement and 104 cases (83.2%) of normal ultrasound. These results are similar to those of Younes et al in Morocco in 2016 on the management of spinal cord compressions of tumor origin who found 18% pathological image with secondary hepatic localizations and lymph node involvement [17]. On the other hand, these results are not similar to those of Alkadi et al in Algeria in 2017 on vertebral metastases which found that pathological images represented 30% of their number consisting only of liver metastases; this can be explained by the fact that their sample was lower than ours [19].
The thoraco-abdomino-pelvic scanner makes it possible to optimize the thoraco-abdomino-pelvic exploration in the search for secondary and lymph node lesions. The thoracoabdominal-pelvic scanner is essential in the study of cancerous disease. In our series 86 cases (68.8%) of thoracoabdomino-pelvic CT scans are normal against 39 cases (31.2%) abnormal among which pulmonary lesions 14 cases (11.2%), bone metastases 9 cases (7.2%), pelvic metastases 6 cases (4.8%), liver metastases 5 cases (4.0%), lymph node metastases 3 cases (2.4%), peritoneal metastases 2 cases (1, 6%). These results are similar to those of Alkadi et al in Algeria in 2017 on vertebral metastases in which we had a 100% achievement rate with 30% pathological images (pulmonary metastases, hepatic metastases, tumor processes of the prostate, supra and sub diaphragmatic lymphadenopathy with multiple bone lesions) [19]. This can be explained by the fact that this examination is essential for an extension assessment.
The most common primary cancer was prostate cancer in 54 cases (43.2%), with adenocarcinoma as the most common histological type in 52 cases (41.6%), followed by breast cancer in 29 cases (23, 2%) with ductal carcinoma as the most frequent histological type in 24 cases (19.2%). These results are similar to several studies including Sidarnet et al in the United States, Younes et al in Morocco, Djiencheu et al in Cameroon which had found that prostate cancer and metastasized the highest level of the spine [14,17,23]. This can be explained by the fact that breast cancer is the most common cancer in women and prostate cancer the most common in men.

Conclusion
Spinal cord compressions of metastatic origin are frequent affections in oncology developing in elderly subjects with a predominance of men. The most common clinical signs are spinal pain, radicular pain, sensory disturbances, motor disturbances and sphincter disturbances. The most common metastatic location was lumbar followed by thoracic location. MRI and CT scans of the spine are the standard examinations because they allow the lesion topography to be determined. The most frequently found primary cancers are prostate cancer with adenocarcinoma as the main histological type, followed by breast cancer with ductal carcinoma as the main histological type.