|Ahead of print publication
Mandibular metastasis as a presenting feature of a clival chordoma
Department of Surgical Oncology, Cancer Institute (WIA), Chennai, Tamil Nadu, India
Cancer Institute (WIA), 38, Sardar Patel Road, Adyar, Chennai - 600 036, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Chordomas are rare tumors which arise from the embryological remnants of the notochord. These tumors can potentially arise from any region within the craniospinal axis and often clinically present as a diagnostic challenge. Chordomas are rare in patients younger than 40 years of age. The most common primary cancers that metastasize to the jaw bones are the ones originating from the breast, lung, kidney adrenal, colo-rectum, or prostate. Mandibular metastasis from a primary chordoma is an extremely rare occurrence with only five prior reports, three originating from primaries in the sacrococcygeal region, one from a lumbar spine primary and the other from a primary arising from the spheno-occipital region. A literature review did not reveal any prior reports of mandibular metastasis at presentation from a clival chordoma. We possibly report the first case of such an unusual clinical scenario in a 7-year-old male child and further discuss the evaluation and management of these rare tumors.
Keywords: Chordoma, Clivus tumors mandibular metastasis, prognosis, skull base tumors
| > Introduction|| |
Chordomas are rare tumors of notochordal origin that account for about 1% of intracranial tumors and about 4% of all primary malignant bone neoplasms. About 32% of chordomas occur intra-cranially, 32.8% are spinal and 29.2% sacral. The most common primary cancers that metastasize to the jaw bones are carcinomas primarily arising from the breast, lung, kidney adrenal, colo-rectum, or prostate. Mandibular metastasis as the first sign of distant metastasis from a primary chordoma is an extremely rare occurrence.,,,, We possibly report the first case of a mandibular metastasis as a presenting feature of a clival chordomain a 7-year-old male child and further review the sparse published literature with regards to the evaluation and management of these rare tumors.
| > Case Report|| |
A 7-year-old male child was referred to our center for further evaluation of insidious onset, swelling in the left hemiface for 3 months. There was a history of a recent increase in size of the swelling for a biopsy elsewhere and also associated with occasional bleeding episodes. The past, childhood developmental, immunization, and family histories were unremarkable. The clinical evaluation revealed a restricted mouth opening due to the presence of a large ulceroproliferative lesion arising from the left lower alveolus, extending from up to the midline anteriorly and reaching up to the left retromolar trigone posteriorly. The well-circumscribed lesion measured about 7 cm × 6 cm and had a large soft-tissue component and was seen to be eroding the underlying mandible. The clinical examination of the neck revealed no significant lymph nodes. A computed tomography (CT) scan of the head and neck region revealed a lytic lesion in the left hemimandible with a large exophytic soft tissue component. In addition, there was a 4 cm × 3 cm × 1.6 cm lobulated soft-tissue lesion in the sellar, suprasellar regions with erosion of the clivus [Figure 1]a and [Figure 1]b. A review of the biopsy report after a clinico-radiological correlation was suggestive of a metastatic chondroma. Microscopic examination revealed areas of stratified squamous epithelium with ulceration. The subepithelium shows the presence of tumor with cells arranged in a lobular pattern with thin fibrous septae. The cells are large, polygonal with abundant bubbly eosnophilic cytoplasm due to vacuolation. The nucleus is vesicular with prominent nucleoli and exhibit moderate polymorphism. Mitotic figures are scanty. Areas of hemorrhage and necrosis are present. Myxoid mucinous material separating the tumor cells is seen in many areas. A patchy lymphocytic infiltration is also present. Immunohistochemical examination showed tumor cells to be positive for cytokeratin, CK 19, epithelial membrane antigen (EMA), vimentin, and S-100. The cells were negative for glial fibrillary acidic protein. About 40%–50% of the cells showed strong immunopositivity for Ki-67. Clinicopathological correlation suggested a diagnosis of a metastatic chondroma. His bone marrow aspiration and biopsies did not reveal any atypical cells.
|Figure 1: (a) Computed tomography scan of the head and neck region revealed a lytic lesion in the left hemimandible with a large exophytic soft-tissue component. (b) Additionally, there was a 4 cm × 3 cm × 1.6 cm lobulated soft-tissue lesion in the sellar, suprasellar regions with erosion of the clivus|
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After a multidisciplinary board consultation, it was decided to consider palliative surgery for the metastatic lesion in the mandible as it was symptomatic and precluded access to the clival lesion. The child underwent a wide excision of the tumor which entailed a left hemimandibulectomy. A primary closure was performed with a decision to consider for a definitive reconstruction subsequently [Figure 2]a, [Figure 2]b, [Figure 2]c, [Figure 2]d. The final histopathology [Figure 3]a and [Figure 3]b after immunohistochemistry correlation [Figure 4] corroborated with the initial biopsy of metastatic chordoma excised with clear margins. The patient subsequently underwent excision of the clival chordoma by an endoscopic transsphenoidal approach and was planned for further radiotherapy. However, within a month of surgery for the clival chordoma, the patient progressively developed widespread metastatic disease (right mandible and lungs). The caregivers opted for best supportive care after extensive counseling; the patient finally succumbed to disease after 3 months.
|Figure 2: (a) Clinical presentation showing the tumor at presentation. (b) Clinical presentation showing the tumor at presentation following the elevation of a cheek flap. (c) Intraoperative picture of the tumor bed following left hemimandibulectomy. (d) Specimen photograph of the left hemimandibulectomy|
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|Figure 3: (a and b) A poorly differentiated malignant tumor. Microscopy shows areas of stratified squamous epithelium with ulceration. The subepithelium shows presence of tumor with cells arranged in a lobular pattern with thin fibrous septae. The cells are large, polygonal with abundant bubbly eosinophilic cytoplasm due to vacuolation. The nucleus is vesicular with prominent nucleoli and exhibits moderate polymorphism. Mitotic figures are scanty. Areas of hemorrhage and necrosis are present. Myxoid mucinous material separating the tumor cells is seen in many areas. A patchy lymphocytic infiltration is also present. The features are suggestive of a metastatic chondroma (H and E X20)|
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|Figure 4: Tumor cells showing immunopositivity to epithelial membrane antigen(EMA), Keratin, S-100 and Ki-67 as labelled in the picture (IHC, ×40)|
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| > Discussion|| |
Chordomas are rare malignant bone tumors that can arise anywhere along the central neural axis. During the normal development, the notochord regresses, nucleus pulposus of the intervertebral disc being the only remnant in adults. Occasionally, the notochord does not completely regress, and additional notochord remnants may persist within the skull base or the spine that can occasionally progress to develop as chordomas.
Chordomas are usually characterized by slow growth and a tendency to be locally aggressive with adjacent bone destruction as was seen in our patient. The clinical presentation of chordomas can vary depending on the location of the tumor. A cranial chordoma may present with symptoms of chronic intractable headaches and cranial neuropathies whereas spinal chordoma may present with symptoms of back pain, sphincter dysfunction, lower extremity weakness, and paresthesias.
Various imaging modalities have been used in the evaluation of chordomas. Plain radiographs may occasionally reveal bony destruction and at times scattered calcifications. On CT imaging, chordomas show hyperdense areas with areas of decreased attenuation and occasionally exhibit an inner calcified matrix. Bony expansion is a characteristic feature in MRI imaging of chordomas. These tumors are hypointense on T1-weighted images and hyperintense on T2-weighted images. In addition, their tumors may demonstrate heterogeneous enhancement on gadolinium-enhanced T1-weighted images. The role of molecular imaging in the diagnosis or treatment of chordoma is scarcely explored and is evolving.
The final diagnosis of chordomas can only be made based on a histopathology/preoperative biopsy aided by immunohistochemistry. Pathologists need to be additionally aware of the various distinct histologic subtypes of chordoma which include chondroid chordomas, cellular chordomas, poorly differentiated chordomas and dedifferentiated chordomas. All chordomas, express cytokeratins and the vast majority of them express EMA and the S100 protein as was seen in our case. The most specific marker of chordoma is brachyury, a nuclear protein associated with notochord differentiation, which has been documented in more than 90% chordomas with a specificity of up to 100%, with regards to differential diagnoses of a chordoma. However, it is noteworthy to mention that poorly differentiated tumors and dedifferentiated areas may demonstrate loss of brachyury immunoreactivity. Brachyury immunohistochemistry was not performed in our patient. However, the classical clinico-radiological presentation of a central neural axis presentation of a clival primary along with the pathology correlation substantiated the diagnosis of a metastatic chordoma.
Chordomas must be differentiated from a variety of other lesions including chondrosarcomas, meningiomas, gliomas, myoepithelial carcinomas, and other metastatic carcinomas.
Chordomas can be divided into three different histological types. Conventional chordomas are slow-growing tumors, while the chondroid variants additionally show areas of chondroid differentiation within an otherwise histologically indistinct conventional chordomas. Dedifferentiated chordomas exhibit features of a high-grade sarcoma alongside features of conventional or chondroid chordomas.
The primary treatment modality for chordomas typically consists of surgical resection followed by adjuvant radiotherapy. An endoscopic approach is the preferred mode of surgery for suspected chordomas of the clivus. Chordomas of the skull base are generally resected in a piecemeal fashion, which often precludes the pathologic assessment of completeness of the margins. Further, complete resection is only achieved in less than one-third of the cases, and most of the tumors invariably have local recurrences despite aggressive multimodality treatment.
Distant metastases from primary chordomas are rare, accounting for about 7%–43% of all the failures, interestingly about three-fourth of the chordomas that metastasize are from sacrococcygeal primaries. The lungs are the most common site of distal metastasis (58%) followed by the lymph nodes (3%), liver (22%), bone (17%), and the skeletal muscle (9%). Distant metastasis as a presenting feature of a chordoma is unusual, and we possibly report the first case of a mandibular metastasis as a presenting feature of a clival chordoma.
Surgery, in the form of a metastasectomy, is occasionally considered for palliation in selected cases of metastatic chordomas as deemed appropriate. In a majority of the reported cases, the jaw metastasis was managed nonsurgically.,, A palliative resection was done in only two of the prior reported patients., Hemimandibulectomy as a part of metastasectomy was considered in our patient in view of the progressive recent increase in the tumor along with associated bleeding.
Chordomas, in general, tend to have a poor prognosis. The 5- and 10-year relative survival rates are 67.6% and 39.9%, respectively, with a median survival of 6.29 years. There are some reports to suggest that younger children are diagnosed with a disproportionately high frequency of poorly differentiated chordomas, which is associated with an overall worse prognosis. The clinical course of our patient was very aggressive; he barely managed to live for 6 months following his initial diagnosis of metastatic disease.
Chordomas have been traditionally considered to be chemoresistant. Earlier studies assessing the efficacy of EGFR inhibitors and imatinib had shown promising results, especially in locally advanced and metastatic chordomas. Despite optimal medical management, most chordomas recur and chordomas, in general, tend to have a poor prognosis. Future strategies will need to focus on alternate strategies including targeted molecular therapies that can potentially better the clinical outcomes of these rare tumors.
All procedures performed in this case report were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Appropriate informed consents have been obtained.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the legal guardian has given his consent for images and other clinical information to be reported in the journal. The guardian understands that names and initials will not be published and due efforts will be made to conceal patient identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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