This chapter focuses on the imaging of malignant lesions arising in bone or soft tissue structures of the skull and aerodigestive tract. Ninety percent of such malignant lesions are squamous cell carcinomas arising from the oral cavity or pharynx; these are dealt with at the end of the chapter.

Malignant Lesions Affecting the Bones of the Skull Base

MULTIPLE MYELOMA

Multiple myeloma, introduced in Chapter 9, is a malignancy of plasma cells found in bone marrow and lymphatics. It occurs in older people and in North America it is approximately twice as common in African-Americans as in Caucasians (3–10 cases per 100,000). This disease most commonly has a widespread distribution through the bone marrow cavities though occasionally can present as a solitary lesion (solitary plasmacytoma). It is the most common primary bone tumor affecting the cranial vault. Myeloma in the calvarium will cause punched-out lucent lesions. These, in advanced cases, lead to a salt-and-pepper appearance. On CT there will be loss of the trabecular pattern in the marrow space (Figure 18.1).¹

CHORDOMA

Chordomas are rare, slowly expansile malignant neoplasms thought to arise from embryonic notochord remnants. They can occur anywhere in the axial skeleton. Thirty-five percent arise in the skull base, predominantly in the midline and usually involving the clivus and/or dorsum sellae.² The average age at diagnosis is approximately 50 years. Chordomas rarely metastasize and are locally aggressive, producing symptoms from cranial nerve compression and destruction of local skull base structures.³ As such, these patients often present with diplopia due to third and sixth nerve involvement.⁴ On computed tomography (CT) chordomas are seen as lobulated midline mass lesions, often with flecks of internal calcification (Figure 18.2a,b). On magnetic resonance imaging (MRI) they are hyperintense on T2-weighted images (Figure 18.2c) with heterogeneous enhancement on postgadolinium sections⁵ (Figure 18.2d).

OSTEOSARCOMA AND CHONDROSARCOMA

Osteosarcoma and chondrosarcoma (introduced in Chapter 10) are the first and second, respectively, most frequent malignant tumors of bone. Despite this, extragnathic osteosarcoma affecting the skull base or vault is very rare; reported cases are often radiation-induced.^6,7 Imaging findings in the skull are similar to those in the jaws.

Chondrosarcomas of the skull base most often arise at synchondroses between membranous bones; especially in the petroclival fissure (Figure 18.3). In contrast to chordomas that occur in the midline, these tumors arise in a paramedian position. Lower-grade lesions expand locally producing cranial nerve deficits much like those caused by chordomas. The higher-grade lesions rarely metastasize, but if they do, it is usually to the lungs. Chondrosarcomas can also occur in the cavernous sinus, superior midline nasal septum, and laryngeal cartilage (Figure 18.4).^8–10 They are composed of chondroid matrix; hence on CT they often con­tain an irreg­ular lattice of internal calcification. Chondrosarcomas are well-circumscribed lobulated tumors that exhibit low to isointense T1-weighted signals, hyperintense T2-weighted signals, and heterogeneous enhancement on MRI.

OLFACTORY NEUROBLASTOMA

Olfactory neuroblastoma (esthesioneuroblastoma) is a malignant tumor arising from olfactory epithelium in the nasal vault; most commonly at the cribriform plate. It is an uncommon lesion, comprising 3% of all intranasal tumors¹¹ and 5–6% of malignant nasal masses. It most often presents with symptoms of unilateral nasal obstruction with or without epistaxis. Due to initial lack of severe symptomatology these tumors present late and are often large at the time of diagnosis. Radiologically these lesions will traverse the cribriform plate, forming an intracranial component.¹² On CT and MRI they vividly enhance, filling one or both sides of the nasal cavity. They are locally invasive (Figures 18.5, 18.6) and will rarely metastasize to retropharyngeal nodes.¹³

NASAL LYMPHOMA

Primary nasal lymphoma is more frequent in East Asians, being quite rare in Caucasians. The most common subtype is diffuse large B-cell lymphoma (Figure 18.7), followed by T-cell natural killer (T/NK).¹⁴ It is mentioned here to point out that lymphoma can mimic many different types of tumors in different parts of the body, and the nasal cavity is no exception. Note the similarity to both olfactory neuroblastoma (see Figure 18.5, 18.6), and sinonasal undifferentiated carcinoma (Figure 18.8). This tumor can also mimic the far more common squamous cell cancer, which also has a high prevalence in East Asians.

SINONASAL UNDIFFERENTIATED CARCINOMA (SNUC)

Sinonasal undifferentiated carcinoma (SNUC) is a bad actor. This extremely malignant neoplasm grows rapidly and metastasizes early (Figure 18.8). It has a poor prognosis despite aggressive multimodality therapy.^15–17. Histologically it is a neuroendocrine carcinoma, belonging to the same group as olfactory neuroblastoma. SNUC accounts for approximately 3% of upper aerodigestive tumors and most often occurs in the nasal cavity. As such, it often exhibits intracranial and orbital invasion when diagnosed.^15,18 The symptoms it produces at presentation are common to other sinonasal diseases (nasal obstruction, unilateral pain, epistaxis). On CT and MRI, these tumors look similar to squamous cell cancer; an enhancing locally destructive mass.

MALIGNANT SALIVARY GLAND NEOPLASMS

Malignant salivary gland neoplasms can be divided into epithelial and nonepithelial tumors. The epithelial neoplasms can be further subdivided into carcinomas that differentiate toward acinar, ductal, myoepithelial, or mixed cell types; low- or high-grade adenocarcinomas; and carcinomas arising from benign mixed tumors (malignant mixed tumors). In most series, mucoepidermoid carcinoma is the most common epithelial salivary carcinoma^19,20 followed by adenoid cystic carcinoma. Other common types of salivary gland carcinomas include acinic cell carcinoma and polymorphous low-grade adenocarcinoma. There are a host of other rare carcinomas including basal cell, clear cell, cystadenocarcinoma, oncocytic, mucinous, salivary duct, sebaceous, squamous, adenocarcinoma not otherwise specified (NOS), myoepithelial, epimyoepithelial, and small and large cell undifferentiated tumors (see later in this chapter). Malignant mixed tumors include carcinoma ex pleomorphic adenoma and carcinosarcoma. Nonep­ithelial tumors include various types of lymphomas and mesenchymal neoplasms, such as malignant schwannomas, fibrosarcomas, et cetera. This classification scheme follows that put forth by Ellis at the U.S. Armed Forces Institute of Pathology (AFIP).²¹ The reader should be aware that there is some variation in the literature regarding nomenclature and classification of salivary gland tumors. For instance, many adenocarcinomas will also commonly be called carcinomas. Adenocarcinoma NOS is a catchall classification for those salivary malignancies that show ductal or glandular differentiation but cannot be easily placed in a specific category. The most common tumors will be described here. In general, the relative incidence of salivary gland malignancy is inversely proportional to the size of the gland with the highest frequency of malignancy found in the minor glands.

MUCOEPIDERMOID CARCINOMA

Mucoepidermoid carcinomas (MEC) are distrib­uted equally between major and minor salivary glands.²² In the major salivary glands, MEC most commonly occurs in the parotid.²³ In the minor salivary glands this tumor vies with adenoid cystic carcinoma for the most frequent malignant neoplasm.²⁴ The average age at diagnosis is 56 years with an age range between 13 and 85 years. MEC occurs sporadically but is also associated with prior exposure to therapeutic ionizing radiation.²⁵ Histologically, MEC contains multi­ple cellular elements including squamous and mucin-secreting cells. The latter cell type accounts for its inhomogeneous enhancement on CT and MRI. Low-grade tumors present as a well-defined heterogeneous mass with sharp margins, low T1-weighted and low T2-weighted signals. Higher-grade—i.e., more malignant—MECs exhibit less well-defined borders with greater enhancement (Figure 18.9).

ADENOID CYSTIC CARCINOMA

Adenoid cystic carcinoma is a slow-growing, insidious, locally invasive tumor. On CT it presents as an enhancing mass, sometimes with adjacent bone erosion (Figure 18.10). On MRI the tumor is usually seen as a T1-weighted hypointense, mildly T2-weighted hyperintense lesion that moderately enhances (see Figure 18.11). These characteristics are not specific and are also seen in other head and neck neoplasms. Lower grade tumors are often well circumscribed and high grade lesions tend to have a poorly defined border. The mean age at diagnosis is 50 years and like mucoepidermoid carcinoma there is a wide age range (13–89 years).²⁶

One particularly bad behavior of adenoid cystic is perineural spread; this is seen in 69% of cases and is associated with increased treatment failures.^26,27 Perineural spread is diagnosed on CT via widening of associated neural foramina (Figure 18.10) and on MRI as postgadolinium enhancement within foramina (Figures 18.11b, 18.12b).²⁸ These findings are often subtle and due to a high pretest probability, a pathologic diagnosis of adenoid cystic carcinoma should prompt careful radiologic examination of all neural foramina associated with cranial nerves that pass through or nearby the lesion. MRI is currently the best modality for this; reaching a sensitivity of 95%.²⁹ Imaging detection of perineural spread is important because 30–45% of perineural invasion is clinically asymptomatic³⁰ and the presence of perineural spread correlates with a decreased 5-year survival rate.³¹ Radiation oncologists will also try to include visible regions of perineural spread in their treatment plan. Perineural spread is also seen with squamous cell carcinoma and occurs much less frequently with other head and neck neoplasms.

ACINIC CELL CARCINOMA

Acinic cell carcinomas are unusually slow-growing neoplasms containing clusters of cells with serous acinar differentiation. The mean age at diagnosis is 52 years.³² The majority occur in the parotid gland (86%),³³ and acinic cell carcinoma is the most common malignant salivary neoplasm to present bilaterally (3% of cases³⁴). On CT and MRI, the appearance is nonspecific, similar to other small benign (and some malignant) salivary gland tumors (Figure 18.13). Diagnosis is usually obtained by fine needle aspiration biopsy.

OTHER RARE MALIGNANT SALIVARY NEOPLASMS

A sampling of rare salivary gland neoplasms are presented in Figure 18.14. The appearance of these lesions correlates with their degree of biological aggressiveness; for example, the mucinous adenocarcinoma in Figure 18.14c is destroying bone, so it is more likely a high-grade lesion. Otherwise the appearance is generally nonspecific with regard to the histological subtype, and diagnosis is made by biopsy or excision rather than by imaging. Figures 18.14a–d are epithelial neoplasms. Figure 18.14e is a nonepithelial tumor: diffuse large B-cell lymphoma.

Squamous Cell Carcinomas of the Aerodigestive Tract

Squamous cell carcinoma (SCC) arises from the epithelial layer of the nasopharynx, oral cavity, and larynx and is the most frequent primary malignancy observed in dental practice. In Canada, an estimated 3400 new cases of oral cancer occurred in 2008 with a 2 : 1 male to female ratio. In 2005, the age-standardized incidence rates for nasopharyngeal, lip, floor of mouth, oropharyngeal, hypopharyngeal, and laryngeal sites were 0.61, 0.76, 0.56, 0.32, 0.55 and 2.85 cases per 100,000, respectively. Up to 95% of these cancers are SCCs.³⁵ The median age at diagnosis is 60 years with a 5-year combined survival of approximately 60%.³⁶ The most important associated risk factors for oral cancer are tobacco and alcohol. Smokers have a 5–25 times higher risk of oral cancer,³⁷ and 75% of all oral cancers are attributable to smoking. Heavy alcohol consumption (>30 drinks/week) increases the risk by 9 times³⁵; combining alcohol and smoking increases the risk by 15 times or more.³⁸ The presence of dentures is not a risk factor in itself though sores caused by ill-fitting dentures have been associated with increased SCC incidence.^39,40 Viral-induced carcinogenesis plays a role; human papilloma virus infection is strongly associated with oropharyngeal SCC.^36,41 Epstein-Barr virus has also been associated with aerodigestive SCCs, particularly in nasopharyngeal carcinoma (NPC: SCC of the nasopharynx), though it is so ubiquitous that it has been hard to prove a causal role.^42–44 For NPC there is a significantly higher incidence in East Asians. It is thought to be related to eating salted fish with high levels of nitrosamines.⁴⁵ The worldwide age distribution for NPC is bimodal with peaks between 15–24 and 65–79 years.⁴⁶

In the aerodigestive tract SCC will typically present a surface abnormality (e.g., erythroplakia, leukoplakia) or a palpable mass. SCC tends to occur in characteristic locations; in the nasopharynx the fossa of Rosenmuller (FOR) is a common site (Figures 18.15–18.17). Posterior NPCs initially produce mild nonspecific symptoms—i.e., Eusta­chian tube obstruction leading to chronic otitis media, referred pain to the ear, or epistaxis. This makes them challenging to discover at an early stage. As the tumor advances it will characteristically begin to invade adjacent cranial foramina, most commonly traveling superiorly through the foramen ovale into Meckel’s cave (the cave of dura mater which contains the trigeminal ganglion) to produce trigeminal nerve symptoms.⁴⁷ From here the tumor can extend into the cavernous sinus, occasionally affecting the intracavernous portion of the abducens (6th cranial) nerve to produce lateral rectus muscle palsy and hence diplopia.⁴⁸ Once in the cavernous sinus, tumor can travel anteriorly to reach the superior orbital fissure and immediately below this extend through the foramen rotundum (Figure 18.16d) into the pterygopalatine fossa. The fossa of Rosenmuller tumor can also travel anteriorly to wrap around the lateral pterygoid plate into the infratemporal fossa. From here cancer can extend medially to enter the pterygopalatine fossa (Figure 18.16a), sometimes connecting to its fellow that has traveled to the same location through the cavernous sinus and foramen rotundum. Tumor in the pterygopalatine fossa can pass medially through the sphenopalatine foramen into the nasal cavity (Figure 18.16a). There are other locations where NPC can enter the skull; sometimes tumor will travel superiorly through the carotid canal, petroclival fissure (Figure 18.16a,c), and/or hypoglossal canal. The latter course will cause hypoglossal nerve dysfunction leading to unilateral tongue atrophy (Figure 18.17a,b). Once inside the skull tumor can elevate the dura (Figure 18.16a), occasionally forming a mass large enough to compress the brain (Figure 18./>