Thoracic dumbbell spinal metastasis secondary to neuroendocrine tumor of unknown origin: Case report and literature review.

Background: Dumbbell tumors are typically benign schwannomas, neurofibromas, and meningiomas and only rarely there are malignant variants of these lesions or other malignant histotypes. Here, a 34-year-old male presented with a thoracic spinal dumbbell metastatic neuroendocrine carcinoma of unknown primary origin. Case Description: A 34-year-old male presented with 2 months of thoracic pain and progressive mid thoracic sensory loss. A post contrast thoracic MRI showed a dumbbell tumor localized between the T7 and T9 levels with extension laterally into the T7-T8 and T8-T9 foramina. The patient underwent a laminectomy for tumor resection following which his pain and gait improved. Histopathologically, the tumor demonstrated multiple rounded small cells with a Ki67 level around 30%, suggesting a malignant metastatic neuroendocrine tumor of unknown etiology.
Conclusion: We successfully treated a 34-year-old male with a T7-T9 malignant spinal dumbbell neuroendocrine tumor of unknown etiology utilizing a decompressive laminectomy. Copyright:

INTRODUCTION

Dumbbell tumors are typically benign schwannomas, neurofibromas, and meningiomas, with occasional malignant variants. Few dumbbell tumors are metastatic neuroendocrine lesions of unknown etiology.[1,3,5,9] Neuroendocrine tumors are epithelial neoplasms originating mainly from the gastrointestinal or bronchopulmonary tracts; they frequently metastasize to lymph nodes, liver, lungs, and bone.[2,5] Here, a 34-year-old male presented with a T7-T9 metastatic neuroendocrine spinal dumbbell tumor of unknown primary origin that was successfully decompressed utilizing a laminectomy.

CASE DESCRIPTION

Clinical and radiographic presentation

A 34-year-old male presented 2 months of mid thoracic pain, gait impairment/ataxia, and hypoesthesia from T11 downward. A post contrast thoracic MRI showed a dumbbell tumor between the T7 and T9 (i.e., maximal width T8) levels contributing to severe spinal cord compression [Figures 1a-d]. This lesion was hypointense on T1/T2-weighted images [Figure 1c], hyperintense on STIR sequences [Figure 1d], and intensely enhanced with contrast [Figures 1a and b]. The whole-body PET-CT-scan revealed multiple diffuse osteoblastic lesions, and the high level of a radioactive tracer involving the 8th/9th ribs bilaterally, sternum, pelvis, and C6-C7 and T3 pedicles.

Figure 1:

Preoperative axial (a) and sagittal (b) thoracic spine MRI sequences showed a T7-T9 intradural extramedullary dumbbell-shaped lesion with intense post contrastographic enhancement. Also, this lesion appears hypointense on T2-weighted images (c) and hyperintense on STIR sequences (d).

Tumor markers

Blood tumor markers, that included beta-2-microglobulin, alpha-fetoprotein, carcinoembryonic antigen, and human chorionic gonadotropin-beta, were negative. Alternatively, serum neuron-specific enolase levels were high (48.4 µg/L; normal range: 0–16.3 µg/L) consistent with a neuroendocrine tumor origin.

Surgery

The patient underwent a T8 total/partial T7-T9 laminectomies to decompress the spinal cord. The tumor was hyper vascularized and there were significant adhesions between the tumor and the dura mater. Ultimately, a partial resection of the extradural lesion was accomplished. Postoperatively, the patient’s gait disturbance and dorsal pain were improved. The 1-week postoperative thoracolumbar MRI documented complete removal of the extradural tumor [Figures 2a and b].

Figure 2:

Postoperative sagittal thoracic spine MRI sequences showed a complete endospecal removal of the lesion images on STIR (a) and T2 sequences (b).

Histology

The histopathological examinations showed multiple round-small cells whose Ki67 level was about 30%, compatible with a neuroendocrine tumor of unknown etiology. Immunostaining showed a positive check for chromogranin and synaptophysin [Figures 3a and b] [Table 1]. The combination of studies allowed for documentation of a well-differentiated neuroendocrine neoplasm (i.e., NEN sec WHO 2019) [Figure 4].

Figure 3:

Immunostaining showed the two most specific and sensitive markers capable of defining the neuroendocrine nature of the neoplasm: Synaptophysin: diffuse and intense cytoplasmic positivity in about 90% of neoplastic cells. (a) Chromogranin-A: granular cytoplasmic positivity (dot-like) in about 90% of neoplastic cells (b).

Table 1:

Immunostaining showed a positive check for chromogranin, synaptophysin, CD56, and PanCK. TTF1, Calcitonin, CDX2, and PSA were found negative, excluding a metastatic tumor from a pulmonary, thyroid, colic, or prostatic primary site.

Figure 4:

Hematoxylin and eosin stain image showed nuclear atypia, with diffuse “salt and pepper” chromatin.

Postoperative course

The patient has started a chemotherapy (i.e., etoposide and cisplatin). After 10 months, his gait ataxia and lower limbs hyposthenia improved. At that point, he underwent a 68 Gallium-DOTATOC positron emission tomography/ computed tomography (PET/CT) that demonstrated stable disease.

DISCUSSION

Tumor presentation

According to the Dumbbell Scoring System, the neuroendocrine tumor presented in this case should be classified as a Grade 5 (size >5 cm, boundary indistinguishable, irregularly lobulated shape, and no osteolytic bone destruction) alternatively, it would belong to Grade 6 of the Eden classification (i.e. due to the multidirectional erosion of the bone).[4-6] The young age of our patient, 34, led to the first diagnostic suspicion of a lymphoproliferative lesion (i.e., lymphoma), but this was ruled out when the whole-body PET CT scan documented multiple bone metastatic lesions.[6-8]

Cases of metastatic neuroendocrine dumbbell spine tumors

We found only two cases of comparable metastatic neuroendocrine dumbbell tumors of unknown origin in the literature.[4,8] Mori et al. reported a 51-year-old female with the sudden onset of paraplegia due to a dumbbell-shaped metastatic extradural lesion at the T10 and T11 levels accompanied by multiple vertebral metastases from a rectal NET.[4] After total tumor excision, the patient recovered and remained free from disease up to 18 months postoperatively. Saway et al. had a 75-year-old male with metastatic Stage 4 pNET, who presented with a cervical intradural-extramedullary metastasis at the C1-C2 level; it was effectively treated with a laminectomy and intradural tumor resection [Table 2].[8]

Table 2:

Literature review regarding dumbbell-shaped tumors.

Markers used to identify of the etiology of neuroendocrine tumors

Neuroendocrine tumors of unknown etiology compromise approximately 10% of all NETs. As they are predominantly undifferentiated, their biological behavior is very aggressive.[1] Urinary 5-hidroxy-indolic acetic can represent a valuable marker in establishing the NET diagnosis.[5] Certainly, the histopathological diagnosis is critical to further define and direct the treatment for Unknown Primary Cancer. Nevertheless, NET metastases carry a very poor prognoses, with 5-year survival rates ranging between 19% and 38%. In our case, the prognosis was supposed to be even poorer (about 11 months) due to the unknown primary.[9] In other rare cases, aggressive recurrences may respond to chemotherapy/radiotherapy protocols as well as surgical intervention.

CONCLUSION

Here, we diagnosed a thoracic T7-T9 malignant metastatic spinal dumbbell neuroendocrine metastatic tumor of unknown origin in a 34-year-old male that was successfully treated with a laminectomy followed by chemotherapy.