When all HNOS, pediatric and adult, are considered together, tumors occur most commonly in the mandible (45–49 %) with the maxilla closely following as the second most common site (47–40 %) [17, 23]. In one of the only reports on pediatric HNOS, of 18 individuals the maxilla and mandible were equally involved (44.5 % each) and other sites were involved 11 % of the time [9]. The majority of patients with HNOS present with a mass lesion or swelling which can be accompanied by pain [12, 15]. Trismus is rarely described as an isolated symptom in HNOS, likely because it is almost always accompanied by pain. It is also important to recognize that symptoms of gnathic osteosarcoma may mimic dental infection. In fact, in one study, 44 % of individuals with these tumors presented to their dentist first for presumed tooth etiology [15]. Other rarer signs and symptoms of HNOS can include cranial nerve palsies, proptosis, or increased intracranial pressure [31].

Like with all osteosarcomas, the etiology for most primary osteosarcoma of the head and neck is unknown. The most significant risk factor for HNOS in children is hereditary retinoblastoma. Other risk factors include prior radiation therapy, and additional cancer predisposition syndromes. Li–Fraumeni and Rothmund–Thomson syndromes predispose individuals to osteosarcoma in general but not specifically HNOS. Paget’s Disease of bone also results in predisposition to osteosarcoma; however, because it causes osteosarcoma in older individuals, Paget’s disease will not be discussed here.

Li–Fraumeni syndrome is an autosomal dominant familial condition involving germline mutations of the TP53 gene that manifests with a very high incidence of malignancies, including osteosarcoma. A study of a large database of TP53 mutation carriers published in 2003 demonstrated that 13.4 % of these individuals with tumors had osteosarcoma [32]. However, the literature does not suggest that anatomic distribution of osteosarcoma in Li–Fraumeni syndrome differs from sporadic osteosarcoma.

Rothmund–Thomson syndrome is an autosomal recessive disorder associated with poikiloderma and other skin abnormalities, as well as bone developmental defects. An increased likelihood of osteosarcoma was first shown in 1990. There are no reported cases of Rothmund–Thomson-syndrome-associated HNOS; rather, these are appendicular skeleton tumors [24].

Hereditary retinoblastoma is caused by a heterozygous germline mutation in the RB1 gene, on the long arm of chromosome 13 [1]. In children who suffer from hereditary retinoblastoma, about 50 % of secondary tumors (after occurrence of retinoblastoma) are osteosarcomas [20]. Originally, the increased risk of osteosarcoma in hereditary retinoblastoma was thought to be strictly secondary to DNA damage inflicted by radiation therapy delivered to the orbit to treat retinoblastoma. However, it is now known that the genetic defect in hereditary retinoblastoma contributes to increased osteosarcoma incidence independent of radiation therapy as demonstrated by an increased prevalence of osteosarcoma in patients with hereditary retinoblastoma at sites distant from radiation fields, such as the extremities. Radiation exposure does further increase HNOS risk in hereditary retinoblastoma. Children who have been irradiated for hereditary retinoblastoma therapy are 2,000 times more likely to get osteosarcoma of the skull than the average person, while they are 500 times more likely to develop osteosarcoma of the extremities [26]. Among children and adults with HNOS, a history of hereditary retinoblastoma is common. Four percent of 173 children and adults with HNOS [23] and 33 % of a group of 18 children with HNOS had a history of hereditary osteosarcoma [9]. While retinoblastoma is almost always diagnosed before the age of five, secondary osteosarcoma may not be diagnosed until adulthood .

Secondary osteosarcoma due to radiation from other pediatric tumors of the head and neck, such as leukemia, brain tumors, and other soft tissue tumors, such as rhabdomyosarcoma, does occur in very small numbers, and the latency period is often a decade or more [34]. It is notable that throughout the literature HNOS secondary to radiation is statistically linked to decreased survival compared to other non-radiation-associated primary HNOS, suggesting that this is a more aggressive tumor type [17, 15].

Complete assessment of a newly identified head and neck bone tumor with imaging is required prior to biopsy in order to allow for appropriate planning of the best biopsy approach. Plain films are a good initial imaging modality to help identify the bone or region of interest for further evaluation and to define the extent of periosteal new bone formation or osteolysis present, but plain films are of limited utility because superimposed bony structures in the head and neck region permit only crude visualization of mass lesions. On cross-section imaging, osteosarcomas typically appear as a tumor arising from bone, causing cortical destruction and resulting in a soft tissue mass containing calcification. Computerized tomography (CT) shows more details of bony involvement and invasion into surrounding structures, and 3D modeling from CT can be helpful for presurgical mapping of the tumor (Fig. 40.2). Magnetic resonance imaging (MRI) provides the most details of soft tissue involvement [9]. Up to 15–20 % of patients with osteosarcoma have metastatic spread at the time of diagnosis; sites of distant metastases in osteosarcoma are, most commonly, the lungs followed by bones. Chest CT and bone scan are performed as part of staging work up to look for distant metastases [42].

Definitive diagnosis of HNOS requires a tissue biopsy. Surgical open biopsy is the traditional approach for obtaining a tissue biopsy. More recently, interventional radiology-guided, percutaneous, core needle biopsy has become a common approach, especially at tertiary care centers with interventional radiology specialists and large volumes of pediatric solid tumor patients. The diagnostic yield of a core needle biopsy is operator dependent and ranges between 78  and 94 % [4, 22, 41]. More recent studies that benefit from updated technology and user familiarity with the technique demonstrate diagnostic percentages on the higher end of this range. Regardless of the biopsy approach, it is important to sample the soft tissue component of the mass if possible, as this usually provides the greatest diagnostic yield. Surgical biopsy is most often incisional rather than excisional given that neo-adjuvant chemotherapy is often given prior to surgical resection. Osteosarcoma has been reported to recur into the tract left by the biopsy apparatus, so it is essential for the physician performing the biopsy, either percutaneously or surgically, to choose an entry point that will be removed en bloc with the tumor when it is surgically excised [8].

Differential diagnosis of HNOS includes other malignant primary bone tumors, other malignancies involving bone, benign bone tumors, and infectious and inflammatory conditions (Table 40.1). On pathologic examination osteosarcoma is a malignant tumor composed of pleomorphic cells associated with osteoid matrix production. Based on the degree of atypia, differentiation, and necrosis, the tumors can be classified as low, intermediate, or high grade. In children, low-grade tumors are very uncommon. In the head and neck, osteosarcomas are usually rich in chondroid matrix (Fig. 40.2) .

One interesting difference between HNOS and osteosarcoma of the long bones is the difference in propensity for metastases, both at time of diagnosis and following initial surgical and/or medical therapy for the primary tumor. The available case series on these tumors, in both adults and children, suggest that metastasis at time of diagnosis is very rare in primary HNOS, as opposed to in osteosarcoma in general, where 25 % of initial diagnoses are made in the presence of distant metastases. In the St. Jude pediatric cohort, none of the 18 patients with HNOS had distant metastases at time of diagnosis [9]. A small case series of five pediatric patients of St. Louis, published in 1973 concluded that none of their cases had metastasized at time of diagnosis [10]. At M.D. Anderson, too, in a cohort of 12 patients between the ages of 12 and 21 years that were retrospectively examined none had evidence of distant metastases at time of diagnosis [21].

In non-head and neck osteosarcoma the standard treatment approach is a combination of systemic chemotherapy and local control, most often accomplished by complete surgical resection with wide margins. The current and historical data show that with surgery alone, more than 80 % of non-head and neck osteosarcoma will recur with distant metastases because of micro-metastatic disease [26]. Chemotherapy when added to surgical resection has been proven to improve overall survival [25]. However, in HNOS some controversy exists regarding whether to administer chemotherapy due to lack of data concerning the utility of chemotherapy in this disease.