Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
______________________
Abstract
The anterior skull base is a complex anatomic site which may be involved by a large number of biologically heterogenous neoplasms. They arise from the epithelium, both surface mucosa and glands, as well as soft tissues, bone, and cartilage. Many benign and malignant tumours in the anterior skull base are similar to their counterparts in other anatomic sites. Interestingly, unique tumours including teratocarcinosarcoma, olfactory neuroblastoma, and angiofibroma can also be found. Recognition of overlapping morphologic features of entities encountered in this anatomic site and the corresponding differential diagnosis is critical. The integration of both morphologic features and immunohistochemical evaluation is essential for correct diagnostic interpretation. This is particularly notable in small round blue cell tumours for which morphologic lineage differentiation is lacking, thus requiring immunohistochemical characterisation. Moreover, challenges in accessing tissue for diagnosis leads to limited biopsies that require proper handling for adequate assessment. Histologic evaluation combined with communication between surgeons and pathologists are necessary components in the work-up and evaluation of these rare tumours.
© 2020 S. Karger AG, Basel
The skull base region comprises diverse structures and tissue lineages that give rise to phenotypically and biologically heterogeneous neoplasms. Histologic classification of tumours arising at these sites may lead to diagnostic challenges especially on presurgical materials [1]. In general, diagnosis of skull base tumours is made by tissue biopsy in the office, operating room, or, in selected cases, by core biopsy under CT guidance. In view of the risk of misdiagnosis, intraoperative diagnosis based on frozen sections should be limited to deep-located lesions, which are difficult to access under local anaesthesia, after an in-depth discussion between the surgeon and pathologist. Tissue biopsies provide limited materials and efforts to ensure proper handling and processing are critical. Accurate diagnosis mandates knowledge, experience, judicial use of lineage and genetic markers, and close interactions between surgeons and pathologists. This pathology paper presents a concise review of the tumours more commonly encountered in the anterior skull base region and their differential diagnosis for practitioners.
Epithelial-Derived Tumours
The majority of epithelium-derived tumours affecting different anatomic sites of the skull base region are malignant. In general, sinonasal carcinomas encompass different types and commonly affect the maxillary sinus (60%), nasal cavity (22%), ethmoid sinus (15%) and, less frequently, the frontal and sphenoid sinuses (3%). Carcinomas arise either de novo from squamous epithelium, squamous metaplasia of respiratory epithelium, or rarely preexisting squamous papillomas, especially the inverted form. The majority of these malignancies are squamous carcinomas and, less commonly, adenocarcinomas and neuroendocrine carcinomas.
Malignant Tumours
Conventional Squamous Carcinoma
Squamous carcinoma typically occurs in elderly individuals in their 6th and 7th decades with a tendency for male gender (M:F 2:1) [1–3]. The most common sites are the maxillary sinus, nasal cavity, and ethmoid, frontal, and sphenoid sinus. Grossly, squamous carcinomas are typical ulcerated and indurate with exophytic features; sinus tumours are bulky and composed of friable light tan tumour tissues [4]. Histologically, tumours typically display squamous differentiation and are graded as well, moderately, or poorly differentiated. Tumours originating from the nasal cavity are generally well differentiated. Tumours of the paranasal sinuses and skull base are commonly non-keratinising carcinomas of intermediate to poor differentiation. Poorly differentiated carcinomas are also called Schneiderian carcinoma and may originate from preexisting inverted papillomas [5, 6]. Rarely, tumours may exhibit spindle cell features and mimic sarcoma or spindle cell melanoma.
Differential Diagnosis
Squamous carcinoma may occasionally pose a diagnostic challenge on small biopsy specimens with sialometaplasia, pseudoepitheliomatous hyperplasia, and Schneiderian papilloma with squamous metaplasia. The common primary lesion to be differentiated in early assessment is inverted papilloma, where a transitional-like squamous proliferation in an inward growth is the typical feature of a lesion frequently observed in the sinonasal tract.
Nasopharyngeal Carcinoma
The histopathologic characteristics of these tumours vary according to the World Health Organisation (WHO) classification [1]. Nasopharyngeal carcinoma is classified into keratinising and non-keratinising phenotypes and corresponds to WHO type I and II/III grades [1]. Pathogenesis is strongly linked to Epstein-Barr virus (EBV) infection and has an ethnic and geographic distribution [7, 8]. Keratinising type (WHO I) is characterised by squamous differentiation showing keratinisation. Non-keratinising types (WHO II and III) are composed of sheets of undifferentiated malignant epithelial cells intimately intermingled with a chronic inflammatory infiltrate which is commonly EBV positive in endemic regions. In situ hybridisation for EBV-encoded RNA is routinely used to identify EBV uniformly in all tumour cells. Serology for EBV-encoded RNA is currently used for follow-up [9, 10].
Sinonasal Undifferentiated Carcinoma
The diagnosis of sinonasal undifferentiated carcinoma is made after the exclusion of morphologically recognised squamous- and glandular-derived carcinomas [11, 12]. Tumours are characterised by primitive malignant epithelial cells with high mitotic figures and cellular necrosis and no squamous or glandular differentiation [13, 14]. Patients are typically elderly males who present with an advanced stage disease. Tumours most commonly originate from the nasal cavity and ethmoid [15, 16]. Grossly, tumours are typically light tan and soft, infiltrative and ill-defined. Histologically, the lesion is composed of sheets of undifferentiated cells with a low nuclear-cytoplasmic ratio, prominent nucleoli, and reticular and clear nuclei with a high mitotic rate and necrosis [15]. Lymphocytic infiltrate may be present associated with epithelial tumour cells, similar to what is observed in nasopharyngeal and human papillomavirus (HPV)-associated oropharyngeal carcinoma [16].
