Skull base chordoma presenting as nasopharyngeal mass with lymph node metastasis.

Spheno-occipital chordomas can rarely present as nasopharyngeal mass. Metastases occur only in advanced disease. They can pose a diagnostic dilemma when information about diagnosis of the primary tumor is not available. We present cytological findings in upper cervical lymph node of a case of nasopharyngeal chordoma and discuss possible differential in such a location.

Introduction

Chordoma is a low-grade malignant tumor that arises from the remnants of notochord. They account for 1-4% of malignant bone tumors and most commonly present after the age of 30 years. Male to female ratio is 1.8:1. Majority occur in sacrum or in the clivus (a bony surface in the posterior cranial fossa sloping upward from foramen magnum to dorsum sella). Those located in the clivus are often associated with a chronic headache and symptoms due to compression of a cranial nerve. Lateral extension can lead to a cerebellopontine angle tumor symptomatology. In case of inferior spread, nasal obstruction, bleeding, and even nasal mass appear.[1] The cytological diagnosis is possible in representative location when physaliferous cells are present and radiological findings are available. But in metastatic sites they are confused with a variety of epithelial mesenchymal tumors, especially when information about the diagnosis of primary tumor is not available. We present cytological findings of a case of metastatic nasopharyngeal chordoma in upper cervical lymph node.

Case Report

A 30-year-old female presented with mild headache, sore throat, gradual onset of difficulty in swallowing and speech for the last 2 years. On examination, a growth was seen behind the uvula obstructing the view of oropharynx with normal overlying mucosa. A level two right cervical lymph node (in the parotid region) was also present.

Routine hematological investigations and chest radiograph was within normal limits.

Computed tomography scan of the neck revealed a well-defined oval-shaped mass 67 × 22 mm in superior nasopharynx slightly to the right side causing pressure erosion of body and lesser wing of sphenoid bone. The mass showed marginal contrast enhancement but no breakdown within. The radiological differentials were nasopharyngeal carcinoma, lymphoma, chordoma, and chondrosarcoma.

Magnetic resonance imaging scan of the upper cervical region revealed a well-defined lobulated space occupying lesion at the skull base near foramen magnum having extension anteriorly along the prevertebral soft tissue having hypointensity in T1 and hyperintensity in T2 and Short T1 Inversion Recovery (STIR) sequence. The lesion also extended intracranially along the anterior aspect of the brain stem and to extra-axial space at C1 and C2 levels involving right lateral recess.

Fine-needle aspiration cytology of the cervical lymph node was done. Aspirated material was clear jelly like. Smears were stained with hematoxylin-eosin and May-Grünwald-Giemsa. Microscopic examination of the smears showed a cellular tumor composed of aggregates and dispersed single cells embedded in abundant chondromyxoid ground substance. The cells were round to oval with bland nuclear chromatin, smooth nuclear membrane, and inconspicuous nucleoli. Mild anisocytosis was apparent. Cytoplasm was clear to eosinophilic. Sparse number of multivacuolated cells was also seen [Figure 1]. Based on these findings a diagnosis of a chondromyxoid tumor was suggested. The possible differential includes salivary gland tumor or metastatic chordoma/chondrosarcoma.

Figure 1

Cytological picture of chordoma showing aggregates and dispersed single cells embedded in abundant chondromyxoid ground substance which appears deep magenta. Multivacuolated cells are well appreciated (MGG, ×100)

A biopsy from the nasopharyngeal mass showed a lobular growth separated by connective tissue septa. The cells were round to oval with vacuolated to eosinophilic cytoplasm and embedded in abundant myxoid matrix. Typical multivacuolated physaliferous cells were appreciable [Figure 2]. Hence, a provisional diagnosis of chordoma was suggested. Mucinous carcinoma, myxoid liposarcoma, and chondrosarcoma were considered among the differentials. Immunohistochemistry was performed that showed positivity with cytokeratin (CK) [Figure 2 inset], vimentin and S-100, thus confirming the diagnosis of chordoma. As surgery was not possible owing to the location of the tumor, the patient underwent radiation therapy.

Figure 2

Histological picture of chordoma (H and E, ×400). Inset shows cytokeratin positivity (IHC, ×400)

Discussion

Chordomas arise from embryonic remnants of notochord and show a dual epithelial-mesenchymal differentiation. In the embryo at 11 mm, the notochord obliterates and is displaced to the cranial and caudal positions. Microscopic foci remain in the vertebral bodies at the cranial and caudal ends of the embryo. Malignant transformation typically occurs in the third to fourth decades of life for spheno-occipital lesions and in the fifth to sixth decades for the sacrococcygeal type.[2] They arise from the sacrum in approximately 50-60% of cases and from the skull base region (spheno-occipital/nasal) in approximately 25-35% of cases.[1]

Chordomas are slow-growing tumors, can invade locally, but rarely metastasize.[3] In advanced disease, metastases to lung, bone, soft tissue, lymph node, and skin occur.[1]

Cytological differential diagnosis includes conventional and myxoid condrosarcoma. The location, which usually is off the midline, and the immunohistochemical features can help distinguish between the two lesions. Characteristic physaliferous cells are not observed. Immunohistochemically, the cells are positive for S-100 and negative for CK and epithelial membrane antigen (EMA). Clinically, these lesions arise in the extremities (mostly in soft tissue) and rarely involve the axial skeleton.[4]

Cells with cytoplasmic vacuoles may be confused with metastatic adenocarcinoma. However, metastatic adenocarcinoma usually lacks typical physaliferous cells, and the extracellular mucin is of the neutral epithelial type, compared with the hyaluronidase-resistant sulfated mucopolysaccharide stroma of chordoma.[5] The cells are negative for S-100.

Vacuolated lipoblasts in myxoid liposarcoma may be mistaken for physaliphorous cells. They lack lobular architecture and evenly distributed physaliferous cells of chordoma. Both tumors are S-100 positive, but myxoid liposarcoma lacks epithelial markers EMA and CK.

Chordoma can also be misdiagnosed as pleomorphic adenoma of salivary gland, as it shows bland epithelial cells and intense fibrillary metachromatic stroma. Presence of multivacuolated physaliferous cells combined with radiological findings can be helpful in this regard. In a review of the fine-needle aspiration cytological features of a case of chordoma and of 17 consecutive cases of pleomorphic adenoma, it was found that the presence of a more abundant, focally vacuolated cytoplasm favors chordoma over pleomorphic adenoma.[6]

Careful staging is a prerequisite for appropriate management. Tumor extent and soft tissue involvement are gauged by radiological modalities. Biopsies are obtained to confirm the diagnosis. The American Joint Committee for Cancer Staging system is generally used.

Treatment options include radiation therapy or combined radiation and surgery, and surgical excision alone. Due to local invasion, many tumors (especially skull base chordoma) often are not amenable to complete surgical excision, and the local recurrence rate is high.[7]

Five-year and 10-year survival rates are approximately 50% and 25-30%, respectively.[8] Some data suggest that female sex, tumor necrosis, and tumor volume of more than 70 mL are independent poor prognostic variables in skull base chordomas.[9]