glands and cords [40–43].
Table 3. Skull base adenocarcinomas
Differential Diagnosis
Sinonasal adenocarcinomas should be differentiated from metastases to the skull base due to salivary and intestinal primaries.
Salivary Gland-Derived Carcinomas
The most frequent phenotype affecting this region is adenoid cystic carcinoma. Adenoid cystic carcinoma typically displays a tubular, cribriform, or solid (or basaloid) pattern. In most adenoid cystic carcinomas, all three patterns can be present, although the distribution greatly varies between different tumours, and even in different areas within the same lesion.
Differential Diagnosis
A diagnostic challenge is mainly encountered with the solid form of adenoid cystic carcinoma, which needs to be differentiated from basaloid squamous carcinoma, malignant melanoma, and neuroendocrine carcinoma. p63 and p40 positivity may direct the diagnosis towards basaloid squamous carcinoma, though this finding can also be present in the myoepithelial component of adenoid cystic carcinomas which has a dual cell population in the tubular and cribriform pattern. Solid adenoid cystic carcinoma is typically derived from the duct-like component and is therefore negative for p63 expression or may show rare positive peripheral cells. Melanoma is positive for melan-A, HMB45, and tyrosinase staining.
Seromucinous Gland-Derived Carcinoma
They are generally low grade and mimic their origin from seromucinous minor glandular structures lining the respiratory mucosa of the ethmoid and maxillary sinuses.
Benign Tumours
Inverted Papilloma
Inverted papilloma is characterised by an inward growth of squamous papilloma with transitional epithelial structures. This lesion is more common in males than females and has a propensity for recurrence and malignant progression. The detection of dysplasia and/or squamous differentiation (keratinisation) is a feature considered to predict malignant transformation. Grossly, inverted papillomas are typically tan to grey polypoid soft tissue masses with a mulberry appearance. These lesions occur in an older age group. Keratinisation may be present in some lesions and this feature may indicate potential progression. A characteristic feature of this lesion is the presence of intraepithelial microcysts with macrophages, cellular debris, and mucin-like materials. Malignant transformation has been reported to occur in 10% of these lesions. Therefore, identification of dysplasia and carcinoma in situ is critical to predict the malignant progression of these lesions. Low HPV subtypes have been identified in inverted papillomas by in situ hybridisations and polymerase chain reactions. No clear association between HPV status and malignant transformation has been established [44–47].
Table 4. Genetic rearrangements of potential clinical significance in skull base malignancies
Pleomorphic Adenoma
Pleomorphic adenoma may develop from minor salivary glands of the sinonasal epithelium, prevalently in the nasal cavity. Involvement of the anterior skull base has been observed, especially in recurrent tumours [48]. The tumour has a similar macroscopic appearance to those of major glands; association with carcinoma should always be excluded by careful analysis of the entire specimen [49, 50].
Soft Tissue Tumours: Malignant Tumours
Malignant soft tissue tumours of the skull base are varied and may not infrequently lead to diagnostic and management challenges. Familiarity and proper use of lineage and molecular testing are critical to their diagnosis (Table 4).
Fibrosarcoma
This is the most frequent mesenchymal malignancy of the sinonasal tract, which more commonly affects the maxillary sinus, nasal cavity, and ethmoid. Grossly, the tumour presents as light-tan and fleshy with a smooth surface with soft-to-firm consistency [51–53]. Histologically, the tumour typically forms sweeping spindle cell interlacing bundles extending to surrounding tissue cells with moderate to low mitotic activity.
Differential Diagnosis
A number of benign and malignant spindle cell tumours which encompass desmoid fibromatosis, sinonasal hemangiopericytoma, solitary fibrous tumours, leiomyosarcoma, and epithelioid haemangioendothelioma must be differentiated from this entity. Distinction between fibrosarcoma and desmoid fibromatosis at this location is based on the sparse cellularity and the fibrotic stroma, while differential diagnosis with leiomyosarcoma is based on the detection of smooth muscle features by immunohistochemistry [54–57].
Rhabdomyosarcoma
Rhabdomyosarcoma is a rare form of sarcoma with skeletal muscle differentiation [58–63]. There are three main histological subtypes that include embryonal, alveolar, and pleomorphic variants. The most commonly encountered subtype in the sinonasal site is the embryonal form, which mainly affects the paediatric age. In adults, the alveolar subtype is more common than the embryonal form. Histopathologically, immunohistochemical markers are crucial to detect primitive skeletal muscle differentiation. Genetically, only the alveolar subtype harbours fusion genes (PAX3-FOXO1 and PAX7-FOXO1) [64–66].
Differential Diagnosis
The embryonal subtype should be differentiated from small cell tumours, olfactory neuroblastoma, small cell neuroendocrine carcinoma, and sinonasal melanoma. As aberrant keratin and neuroendocrine markers (synaptophysin/chromogranin) may occur in the alveolar subtype, immunohistochemical assessment for muscle markers (desmin/myogenin) is critical to this diagnosis.
Synovial Sarcoma
Synovial sarcoma may involve the skull base region as extension
