Malignant Transformation of Primary Spinal Teratoma with Intracranial Metastasis: A Case Report and review of the literature

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Case Report

Malignant Transformation of Primary Spinal Teratoma with Intracranial Metastasis: A Case Report and review of the literature

https://doi.org/10.21203/rs.3.rs-3780400/v1

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Primary spinal teratoma is a rare disease, and there have been no reported cases of malignant transformation in the literature. We present a case of a 66-year-old female patient who had been experiencing numbness in her right lower limb. The patient underwent surgical resection. The pathological report confirmed a mature teratoma. However, at the 7th month after the surgery, the patient's tumor has recurred, leading to a second surgery. Postoperative pathology revealed malignant transformation of the teratoma into squamous carcinoma. Four months after the second surgery, the patient developed symptoms such as dizziness and vomiting. Head magnetic resonance imaging indicated multiple intracranial metastases. By summarizing the reports on this case and relevant literature, the aim is to provide corresponding guidance for clinical physicians.

Spinal teratoma Malignant transformation Intracranial metastasis

Primary spinal teratomas are an exceedingly rare form of central nervous system tumors, constituting approximately 0.5% of all spinal cord tumors. Mature teratomas are characterized by the presence of tissues derived from three germ layers¹As mature teratomas are a benign condition, the prognosis is generally favorable, with very few instances of recurrence, and even fewer cases demonstrating malignant transformation². In this report, we present a case of a middle-aged female patient was diagnosed with a mature teratoma following her initial surgery, However, she experienced a recurrence seven months later, with pathological confirmation of malignant transformation into squamous carcinoma. Furthermore, the patient developed intracranial metastases. Through this literature, our aim is to enhance the clinicians' understanding of spinal teratomas, provide valuable insights into the clinical presentation, diagnostic approaches, and treatment choices following malignant transformation, and ultimately offer more precise guidance for the postoperative follow-up and management of spinal teratoma patients.

The patient is a 66-year-old female who initially complained of right lower limb weakness accompanied by urinary retention issues. Following a lumbar spine MRI scan, an abnormal signal was detected within the spinal canal at the level of L5 to S3 vertebral bodies, suggestive of a space-occupying lesion. Subsequently, surgical resection was performed, during which the tumor was successfully excised with intact preservation of the cauda equina nerves. After the surgery, the patient's lower limb muscle strength recovered, and urinary and fecal dysfunction improved. The pathological report indicated the presence of predominantly keratinoid material, as well as partial epithelial and adipose tissue, consistent with changes indicative of mature cystic teratoma (Fig. 1a).

However, seven months postoperatively, the patient experienced a recurrence of symptoms, including bilateral lower limb weakness and urinary retention. The lumbar spine MRI scan revealed spinal cord thickening from the T12 to L1 vertebral levels with an internal abnormal signal appearing isointense on T1WI and slightly hypointense on T2WI, with poorly-defined borders (Fig. 2). In order to determine the nature of the tumor, the patient consented to undergo a second intraspinal lesion excision surgery. Intraoperatively, the tumor was observed located dorsally to the spinal cord, appearing pale yellow, with indistinct boundaries from the spinal cord. Under the microscope, meticulous dissection of the tumor periphery, spinal nerve roots, and nerve fibers within the tumor was performed, followed by tumor removal. The tumor was noted to be hard and tough in texture. Following the tumor excision, no signs of spinal cord pulsation recovery were observed. (Fig. 3). After the surgery, physical examination revealed Grade I muscle strength in both lower limbs of the patient, along with decreased superficial sensation bilaterally, accompanied by urinary and fecal dysfunction. Subsequent pathological examination revealed infiltrating squamous cell carcinoma within the tissues, with immunohistochemistry showing CK-pan(+), CK7(-), CK5/6(+), P63(+), P40(+), P53(-), and Ki-67(+ 60%), indicative of malignant transformation of teratoma cells within the spinal canal (Figure 1b).

The patient was discharged, but four months later, she developed symptoms of headache, nausea, and vomiting. A head MRI scan revealed multiple nodular mixed abnormal signals in the right cerebellar hemisphere and bilateral temporal lobes, measuring approximately 1.2x1.4cm, 2.2x2.5cm, and 2.3x2.9cm, respectively. These nodules appeared slightly hypointense to low signal on T1WI, high signal to isointense on T2WI,strongly suggestive of brain metastases from cancer (Figs. 4). Subsequently, the patient received further treatment for intracranial metastatic tumors in the radiation oncology department, with a PGTV (Planning Gross Tumor Volume) single dose of 600cGy administered in 5 fractions, totaling 3000 cGy. The patient was discharged after improvement in clinical symptoms following treatment.

Epidemiology

Teratoma is an exceedingly rare type of tumor within the entire central nervous system. Central nervous system teratomas account for only 2% of all teratomas. It primarily affects young children, with a higher incidence in intracranial locations than in the spinal cord. Intracranial teratomas typically develop along the midline, including regions such as the pineal area, saddle area, fourth ventricle, and basal ganglia. Spinal cord teratomas are mainly prone to occur in the sacrococcygeal region in neonates, and in adults, they tend to occur more frequently in the thoracolumbar region^1–3.Teratomas in the spinal cord can be located either intradurally (within the dura mater) or extradurally (outside the dura mater). Tumors occurring within the dura mater can be situated within the spinal cord (intradural-intramedullary) or outside the spinal cord (intradural-extramedullary) ⁴.

Clinical feature

The clinical presentation of spinal teratomas primarily depends on the location of the tumor along the spine. Patients with teratomas affecting the lumbar spine may experience symptoms such as difficulty urinating, lower limb numbness, weakness, loss of deep sensation, and loss of superficial sensation. In cases where teratomas affect the cervical spine, patients may present with quadriplegia and sensory disturbances in all four limbs. During a physical examination, some patients may exhibit hyperactive deep tendon reflexes and ankle clonus ⁴.

Auxiliary examination

Preoperative evaluation of teratomas primarily relies on spinal MRI (Magnetic Resonance Imaging). Teratomas consist of a combination of fatty, calcified, and cystic components, resulting in a heterogeneous signal on MRI scans. Wang et al. summarized the radiological features of teratomas, which include:

1.Well-defined borders, presenting as thick-walled, round, or lobulated cystic masses.2.Presence of fatty tissue, appearing as high signal on both T1WI and T2WI, and low signal on fat-suppressed sequences.3.Calcified tissue displaying low signal on both T1WI and T2WI.4.Mild enhancement on contrast-enhanced scans.5.Sometimes associated with congenital spinal abnormalities.These MRI characteristics help in identifying and characterizing teratomas within the spinal cord⁵.

In this case, the patient experienced malignant transformation of the teratoma. On MRI, compared to benign mature teratomas, malignant teratomas exhibit indistinct borders and uneven enhancement on contrast-enhanced scans. Therefore, in patients undergoing teratoma resection and follow-up, the presence of these characteristics should raise suspicion of malignant transformation. However, a definitive diagnosis primarily relies on postoperative pathological biopsy.

Origin

There is a certain controversy regarding the origin of spinal teratomas, and currently, there are two main theories.

Dysembryogenic Theory: This theory suggests that spinal teratomas originate from the disordered differentiation of pluripotent stem cells within the primitive streak or caudal cell mass. Some observations support this viewpoint. Spinal deformities are often associated with spinal teratomas, which are considered evidence for the Dysembryogenic Theory. Furthermore, the incidence of teratomas at different locations along the spine gradually decreases as the distance from the lumbar or conus regions adjacent to the tail cell clusters increases ⁶.

The misplaced germ cell theory posits that teratomas originate from pluripotent primordial

germ cells. Under normal circumstances, primordial germ cells migrate from the yolk sac to the genital ridge. However, when this migration occurs abnormally and the primordial germ cells reach the dorsal midline instead of the intended destination, it leads to the development of spinal teratomas⁷. While teratomas can be associated with spinal deformities, it is more common for patients with spinal teratomas to have no spinal developmental abnormalities. Therefore, it is believed that teratomas without spinal deformities may originate from germ cells⁶.

Pathology

According to the latest WHO CNS5 classification, teratomas are categorized into three main groups: mature teratomas, immature teratomas and teratoma with somatic-type malignancy (previously teratoma with malignant transformation) ⁸.Mature teratomas are typically benign, comprised of well-differentiated tissues derived from all three germ layers, including mature bone, cartilage, epithelial, and smooth muscle tissues. In contrast, immature teratomas are regarded as malignant due to the presence of primitive, undifferentiated cells ,such as immature neural tissue, cartilage, and nerve tissue ⁹. Teratoma with somatic-type malignancy, also known as malignant transformation in teratoma, encompasses malignant components such as rhabdomyosarcoma, immature teratoma, and squamous cell carcinoma.

Mature teratomas generally present as benign tumors and rarely undergo malignant transformation. Existing literature reports that approximately 1.5–2% of cases of ovarian teratomas undergo malignant transformation ¹⁰.There are currently no reported probabilities of malignant transformation in central nervous system teratomas. The prognosis of patients is closely associated with their pathological subtypes. It has been reported that mature teratomas have a 10-year survival rate exceeding 90%. In contrast, immature teratomas exhibit a 5-year survival rate of 70%. Teratoma with somatic-type malignancy, on the other hand, carries a poorer prognosis ⁹.

Treatment

At present, the treatment strategy for spinal teratomas recommends early tumor resection. During surgery, the foremost objective is to maximize tumor removal while preserving function. This approach is motivated by several key considerations:

Tumor volume tends to increase over time, it has been reported that the average annual growth rate is approximately 1.8 mm per year ¹¹. As the tumor volume increases, it can exert pressure on the nerves, leading to impaired neurological function and, in severe cases, irreversible damage. Additionally, the potential risk of malignant transformation in teratomas can directly lead to an adverse prognosis for the patient. Hence, early surgical intervention is strongly recommended.

For the extent of intraoperative tumor resection, the ideal scenario involves achieving complete tumor removal. It offers several advantages, including maximal decompression, minimized risk of tumor recurrence, metastasis, deterioration, and facilitates postoperative pathological assessment. However, it is essential to acknowledge that in the majority of cases, tumors exhibit significant adherence to the spinal cord, with reported adherence rates of approximately 50% ¹². This inherent challenge often makes the achievement of complete tumor resection difficult. Post-resection, there are potential risks of complications, such as paraplegia and urinary and bowel dysfunction. Additionally, owing to the slow growth pattern of mature teratomas, reported recurrence rates for complete and subtotal resection are relatively similar at 11% and 9%, respectively¹². Therefore, the primary goal during surgery should be to maximize tumor removal while preserving neurological function

Regarding postoperative adjuvant therapy, due to the slow growth and low recurrence rate of mature teratomas, routine postoperative radiation or chemotherapy is generally not recommended in most reported cases ^4,12.For immature teratomas, radiation therapy (radiotherapy) can be considered as a part of the treatment2. In the report by Kawai et al., it was noted that postoperative patients who experienced recurrence were managed with a combination of radiotherapy and chemotherapy, leading to symptom relief and a reduction in tumor volume ¹³.In this case, surgical resection was undertaken for the recurrent teratoma. The primary advantage of this approach was obtaining a definitive pathological diagnosis, which would help guide further treatment. However, postoperatively, the patient's issues, including muscle weakness, did not show significant improvement.

Postoperative follow-up.

Given the extremely low incidence rate of this condition, there is currently no clear expert consensus to guide further follow-up at this stage. In light of the specific case, the patient experienced a recurrence of spinal cord compression symptoms, brain metastasis, and malignant transformation of the tumor only four months after the second resection. Similarly, Kawai et al. reported a case where tumor recurrence occurred again three months postoperatively, along with intracranial metastasis¹³.This patient did not undergo surgery to confirm its pathological nature. Considering these two cases, for mature teratomas, long-term radiological follow-up is recommended postoperatively, particularly for patients who underwent subtotal tumor resection. If there is a recurrence of spinal cord compression symptoms shortly after surgery, it suggests the possibility of tumor recurrence. Radiologically, the presence of abnormal enhancement may indicate malignant transformation. A repeat surgery for pathological diagnosis may be warranted. Additionally, since there is a risk of intracranial spread in this condition, it is advisable to include comprehensive head MRI as part of the evaluation.

Ethics approval and consent to participate

The patients reported in this article have obtained verbal informed consent. Therefore, it does not require approval from an ethics committee.

Consent for publication

Informed consent to publish the identity revealing information / images were obtained from the participant.

Availability of data and materials

Data sharing is not applicable to this article as no new data were created or analyzed in this study.

Funding

This study did not receive any specific grant from funding agencies in the public, commercial or non-profit sectors.

Authors' contributions

Songbai Xu: Conceptualization, literature review, and manuscript writing.

Liu Yang: Review of clinical case studies, data analysis, and manuscript editing.

contributed equally to manuscript writing, editing, and formatting.

Bo Liu and Xuanyu Tan provided expertise in specific field, contributed to the interpretation of results, and critically revised the manuscript for important intellectual content.

Peilin Shan,Junjie Fengand BoYu contributed to the literature review, ensuring comprehensive coverage of previous cases relevant to the patient's condition.

All authors have reviewed and approved the final version of the manuscript.

Competing interests

The authors declare that there is no conflict of interest.

Acknowledgements

I would like to express my sincere gratitude to Dr. Yuxiong Wang for his invaluable assistance in reviewing and editing this manuscript. His expert insights and guidance were instrumental in improving this research work.

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No competing interests reported.

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Malignant Transformation of Primary Spinal Teratoma with Intracranial Metastasis: A Case Report and review of the literature

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