“Twins Intramedullary Tumors”: Case Report of a Double Spinal Metastasis from Breast Cancer. Technical Nuances and Review of the Literature Case

cancer, we have operated on for two adjacent cervical ISCMs. To our knowledge, this is the first surgical case reported in literature of a double intramedullary metastatic disease, with the two separate lesions occurring simultaneously. The aim of our paper is to describe the clinical features and radiological findings of metastatic intramedullary breast carcinoma, as well as surgical technique with emphasis on intraoperative neurophysiological monitoring (IONM) and a wide literature review about ISCMs from breast cancer. AbsTRACT Pizzuti V, Ricciardi F, D Elia A, Fabbiano F, Innocenzi G. “Twins Intramed ullary Tumors”: Case Report of a Double Spinal Metastasis from Breast Cancer. Tech nical Nuances and Review of the Literature .

Surgery aims at decompression of functional neural tissue and histological confirmation of the tumor [9]. Metastatic localization of a malignant disease is usually solitary and at clinical onset the patient has systemic widespread with secondary localization to lung, liver, bones and brain [10]. In this report we describe the case of a 49 year-old woman, affected by breast cancer, we have operated on for two adjacent cervical ISCMs. To our knowledge, this is the

Intramedullary spinal cord metastases represent a small
proportion of intramedullary tumors, accounting for 0.9-5% of all spinal metastases [3,6,11]. Development of an ISCM is still a rare event in the course of a malignant disease. Nevertheless, due to both increasing survival of patients with malignant tumors and widespread MRI availability, incidence of ISCM is rising [4,5,11].
Three different routes for the spread of tumor to the spinal cord have been hypothesized, among which the hematogenous dissemination through the arterial route is considered to be the most common one [2,3,[6][7][8][12][13][14][15]. The second mechanism is related to the leptomeningeal dissemination by the cerebrospinal fluid (CSF) [3,6,14]. Thirdly, direct invasion by a metastatic tumor from the spinal extradural space or CSF or nerve roots, through the dura and into the cord, and spread to the subarachnoid space and spinal cord parenchyma, has been suggested [14,16].
ISCMs are often asymptomatic, and clinically affect less than 1% of patients with metastatic cancer [5,6,17]. At time of presentation, weakness is present in 93%, sensory loss in 78% and urogenital dysfunction in 62% of patients [4,7,10,13,18]. Rapid progression of the symptoms distinguishes ISCMs from primary intramedullary neoplasms, which are typically characterized by a slower progression [10,13]. At the time of diagnosis, most of the patients have systemic metastases to lungs, liver and bones, and nearly half of them have brain metastases [7,12,17]. For this reason, imaging modalities should be extended to the entire spinal cord and brain, and the whole body needs to be investigated to detect any further dissemination. Prompt and accurate diagnosis is crucial for  [8,16,20]. It is now widely accepted that early surgical intervention is indicated for all patients who present with rapid progressive neurological impairment [4].
Moreover, the development of intraoperative neurophysiological monitoring (IONM) of sensory and motor functions and the use of ultrasonic aspirators have been crucial to guide and perform surgical resection as the first line treatment for these challenging lesions [21]. Despite this, surgical therapy can be performed in selected cases only, and several factors should be taken into account when considering it, such as age and performance status of the patient, prognosis, as well as location and severity of the primary tumor, anesthesiologic and surgical risks [4,8,15,22,23]. The concept of spinal instability is also critical in the surgical decisionmaking process.
In order to predict spinal instability due to neoplastic lesions, potentially useful for preoperative evaluation of metastatic spine tumors prognosis [25]. In 2005, the authors revised the system [26] by correlating the following parameters with survival period: general medical conditions, number of extraspinal bone metastases, number of metastases in the vertebral body, metastases to the major internal organs such as lungs and brain, primary site of cancer and severity of spinal cord impairment. Each parameter ranged from 0 to 5 points, and the total score was 15 points. Conservative treatment or palliative procedures were indicated with a total score of 8 or less or those with multiple vertebral metastases, while excisional procedures were suggested in patients who scored 12 or more, or in those with a total score of 9 to 11 and with metastases in a single vertebra [26]. Despite most of ISCMs are well encapsulated and can be safely removed, Gasser et al. [9] noted that tumor histology also influenced the extent of resection and radicality. They found that poorly differentiated carcinomas and sarcomas were difficult to dissect due to the lack of a clear border between the tumor and the spinal cord, as well as an increased likelihood of clinical deterioration after lesion resection in these patients [9].
According to the authors, complete surgical removal should be reserved for those cases where a clear plane of cleavage allows a safe microsurgical dissection of the lesion [9], whereas biopsy, decompressive laminectomy and adjuvant therapy may prove as valuable alternatives to radical resection in the remaining cases [9]. Radiation therapy and chemotherapy are considered for adjuvant treatment for ISCMs patients. Post-operative conventional external beam radiation therapy has been the standard of care [27], especially considered for radio-sensible cancers such as small cell lung and breast carcinomas, and lymphomas. However, technical improvements have allowed for the application of the stereotactic body radiotherapy (SBRT) to the spine, which delivers several fold greater biological effective doses [27]. Outcome data show higher rates of local control and pain control for patients treated by SBRT, and suggest better efficacy than with conventional palliative radiotherapy [28,29], with vertebral compression fractures being the most concerning adverse event, usually observed in 10-15% of patients [27]. Adjuvant radiation therapy (total dose 30-40 Gy) may be also useful for residual tumor after surgery and recurrent tumor, but controversy exists regarding this treatment [30]. Boström et al. [31] reported 70 cases of intramedullary spinal cord tumors, among which 8 were represented by carcinoma metastases. Adjuvant therapy in the form of radiotherapy was administered in 5 out of 8 cases, while 2 patients received adjuvant chemotherapy and the remaining one underwent palliative chemotherapy alone [31].
Although standards of treatment have improved in these years, prognosis of ISCMs remains poor, and median survival varies from 9.4 months when patients have undergone surgery to 5 months when conservative treatment only has been adopted [4].So far, few papers have been published about surgical resection of ISCMs.
Hrabalek [12] reported 42 references of 87 ISCM surgically treated up to January 2009, found through a biomedical database search [12]; they only found 13 references of 27 cases with diagnosed and treated ISCMs of breast carcinoma. In 2013, Rostami et al. [32] found a total of 36 papers, among which 19 were single case reports or small case series exclusive of breast cancer metastases [33].
Breast cancer shows a high propensity to spread to the central nervous system (CNS) during its course [32]. Nonetheless, ISCMs  [19] reported solitary metastases in 39 (80%) cases and multiple ISCMs in 10 (20% of patients).
In our literature review, we found only one case report about a surgically treated double intramedullary metastasis in patient suffering from breast cancer, but the repetitive lesions occurred separately, each of which as a solitary lesion [36]. In contrast, we reported the treatment of two different intramedullary metastases occurring at the same time. These lesions were very close, resembling twins, and this is the reason why we called them "twins' tumors". To our knowledge, this is the first case report describing such phenomenon. In addition, the masses were very different in terms of consistency, thus requiring two different surgical strategies to obtain radical resection. The first, superior mass, was soft and

Conclusion
This is the first case described in literature where two different intramedullary metastases from breast cancer occurred simultaneously, in absence of any other systemic repetitive lesion.
We reported two different modalities of surgical resection of ISCMs, with and without ultrasound aspirator, used during the same operation, with side effects of this surgical tool on spinal cord parenchyma, as demonstrated by IONM. Our report highlights the importance of using multimodal IONM in order to improve the safety of the surgical procedure, preserving neuronal structures and achieving an optimal postoperative outcome [37]. The use of ultrasound aspirator should be limited to those tumors whose firm consistency prevents other surgical strategies to be applied.

Conflict of interest
We have no disclosure to make that qualifies as a conflict of interest.