in nature. Complete excision with negative margins is often difficult to achieve [94–97].
Epithelioid Haemangioendothelioma
This entity is very rare but may lead to challenges in differential diagnosis. The epithelial-like cellular features may erroneously orient towards an epithelial malignancy. The finding of intracytoplasmic vascular features aided by immunohistochemistry is critical to a timely diagnosis. These tumours display a low-grade malignant behaviour and should be completely excised [98–102].
Meningioma
The majority of meningiomas of the skull base sites are typically an extension from an intracranial primary. Primary meningiomas are rare and most likely arise from ectopic meninges and arachnoid cell rests of cranial nerve sheaths. An origin at the transition between endoneurium of the olfactory nerve and cribriform plate has also been suggested.
At histology, skull base extracranial meningiomas are morphologically identical to their intracranial counterpart, but tend to be locally invasive, frequently showing characteristic whirling. They are typically meningothelial or fibroblastic, but other types may also be found [103–106].
Angiofibroma
Angiofibroma is a benign vascular lesion that typically affects young males within the age range from 9 to 18 years. The epicentre of the lesion is located at the level of the pterygopalatine fossa, but extension to the skull base is observed in 20–25% of patients. Angiofibroma commonly appears at nasal endoscopy as a hypervascularised polypoid lesion with well-defined margins and no presence of necrotic areas. Hormonal aetiology may play a role in its development. Histologically, angiofibroma is made by numerous thin-walled vessels of varying shapes and sizes embedded in a collagenous tissue.
Neuroectodermal Neoplasms
These tumours are of neuroglial origin and manifest as a primitive small cell growth. This morphologic similarity may lead to misclassification. The most frequently encountered entities at the skull base are olfactory neuroblastoma and the primitive neuroectodermal group of tumours.
Olfactory Neuroblastoma
This entity arises from neuroepithelium in the upper aspect of the nasal cavity and roof of the nose and the cribriform plate of the ethmoid sinus. Olfactory neuroblastomas comprise approximately 5% of sinonasal tract malignancies [107–109], and equally affect both genders with bimodal age clustering in the 1st and 2nd and the 4th and 5th decades of life. The tumour presents as a unilateral nasal mass with obstruction and bleeding symptoms [110–112]. Grossly, olfactory neuroblastomas are light tan and soft tissue masses. Histologically, the lesion is composed of small uniform sheets and nests of primitive basal cells with minimal cytoplasm with a neurofibrillary background and occasionally with neuroepithelial pseudo-resetting features (Homer-Wright structure). True rosette formation with duct-like spaces (Flexner-Wintersteiner rosette) are rare. High-grade tumours are characterised by large pleomorphic cells and necrosis [113, 114].
Ancillary markers for diagnosis include keratin, synaptophysin, and other neuroendocrine and muscle markers (Table 2). Amplification of c-Myc oncogene and loss of chromosome 1p have been considered poor prognostic markers.
Differential Diagnosis
Tumours to be differentiated from olfactory neuroblastoma include lymphoma, melanoma, small round cell (Ewing’s sarcoma/PNET) tumour, rhabdomyosarcoma, and adenoid cystic carcinoma (solid form). Immunohistochemical profiles including a spectrum of different cell lineages are crucial for diagnosis. The comparative characteristics of these tumours with other primitive sinonasal tumours are presented in Table 5.
Ewing Sarcoma/PNET
Ewing sarcoma and PNET are interrelated primitive round cell malignancies of neuron-ectodermal derivation [115–117]. They represent a spectrum of morphologic entities that share common molecular genetic features. These tumours rarely involve the skull base, mainly as a secondary extension from sinonasal localisations, and typically occur in childhood and young adults. The maxillary sinus and the nasal fossa are the most commonly affected sites. Grossly, tumours present as light-tan, soft, and fleshy tissues with haemorrhage and mucosal ulceration.
Table 5. Immunomarkers in the differentiation of small round cell tumours
Histologically, the tumour presents in sheet and nests of densely uniform small cell proliferation. CD99 (MIC2) is commonly used and generally positive. PCR-based methods to detect the EWS/FLI gene fusion transcript and in situ hybridisation of chromosomes t(11;22) or t(21;22) is helpful in confirming the diagnosis (Table 5).
Differential Diagnosis
The differential diagnosis includes all small round cell tumours, lymphoma, melanoma, rhabdomyosarcoma, small cell carcinoma, and pituitary adenoma. A combined panel of cytomorphologic and immunohistochemical markers is sufficient to establish the diagnosis.
Paraganglioma
Sinonasal and skull base paragangliomas are extremely rare. They are likely to be derived from dispersed neuroendocrine cells within the sinonasal mucosal covering. Tumours at this location may behave in an aggressive fashion. All paragangliomas are considered malignant in the new WHO classification.
The histologic characteristics of these lesions are typical of those in traditional sites with classical Zellballen organisation and granular cytoplasm [118–120]. Immunohistochemically, cells comprising these tumours are positive for neuroendocrine markers and negative for keratin. A helpful feature is the positivity for S-100 protein in sustentacular cells bordering the Zellballen.
Mucosal Melanoma
Primary melanoma in the sinonasal tract accounts for less than 1% of all melanomas [
