Head and neck sarcomas

INTRODUCTION — Head and neck sarcomas are rare tumors, and this makes rigorous study of clinical behavior difficult. As a result, treatment algorithms are drawn from retrospective case series and principles are derived from treatment of sarcomas at other sites, rather than from large clinical trials. Their study is also made more difficult by the diversity of histologic subtypes and the variable clinical behavior. Furthermore, the confining anatomy and proximity to vital structures makes even adherence to traditional margin-driven therapy challenging.

The demographics of head and neck sarcomas, the clinical behavior of the common subtypes, and general treatment principles will be reviewed here. An overview of the epidemiology, clinical presentation, histopathology, diagnostic evaluation, and staging of soft tissue and bone sarcomas, and a discussion of treatment for sarcomas arising at other sites are discussed elsewhere.

●(See "Clinical presentation, histopathology, diagnostic evaluation, and staging of soft tissue sarcoma".)

●(See "Osteosarcoma: Epidemiology, pathology, clinical presentation, and diagnosis".)

●(See "Chondrosarcoma".)

●(See "Rhabdomyosarcoma in childhood and adolescence: Epidemiology, pathology, and molecular pathogenesis" and "Rhabdomyosarcoma in childhood and adolescence: Clinical presentation, diagnostic evaluation, and staging".)

●(See "Epidemiology, pathology, and molecular genetics of Ewing sarcoma" and "Clinical presentation, staging, and prognostic factors of Ewing sarcoma".)

●(See "Overview of multimodality treatment for primary soft tissue sarcoma of the extremities and superficial trunk".)

●(See "Clinical presentation and diagnosis of retroperitoneal soft tissue sarcoma".)

●(See "Bone sarcomas: Preoperative evaluation, histologic classification, and principles of surgical management".)

EPIDEMIOLOGY, HISTOLOGIC DISTRIBUTION, AND RISK FACTORS — Sarcomas of the head and neck account for about 2 percent of all head and neck malignancies and 4 to 10 percent of all sarcomas in adults [1-3].

Approximately 1000 cases of head and neck sarcoma are diagnosed each year in the United States and comprise about 10 main histologic subtypes and many minor subtypes. The main histologic subtypes are rhabdomyosarcoma (RMS) in children; osteosarcoma (and chondrosarcoma); vascular sarcomas (especially angiosarcoma and Kaposi sarcoma), and also, the common adult soft tissue sarcomas (undifferentiated/unclassified sarcomas; liposarcoma; leiomyosarcoma [LMS]; synovial sarcoma; and malignant peripheral nerve sheath tumors [MPNST]). In series in which desmoid tumors (aggressive fibromatosis) and dermatofibrosarcoma protuberans (DFSP) are included, these tumors account for a large proportion of cases. Other less commonly occurring sarcomas include solitary fibrous tumor, Ewing sarcoma, and alveolar soft part sarcoma. (See "Clinical presentation, histopathology, diagnostic evaluation, and staging of soft tissue sarcoma", section on 'Histopathology' and "Chordoma and chondrosarcoma of the skull base" and "Osteosarcoma: Epidemiology, pathology, clinical presentation, and diagnosis", section on 'Histologic classification'.)

The clinical and histologic makeup of any of the large series of head and neck sarcomas is highly dependent upon the nature of the reporting institution or the clinical practice of the reporting clinician [4-14]. General oncologic surgeons are likely to see a different array of patients compared to otolaryngologic surgeons, pediatric surgeons, or plastic surgeons. Many series exclude bone sarcomas or benign or low malignant potential tumors (eg, desmoid tumors and DFSP). Some series include pediatric sarcomas and thus have a very large proportion of RMS; others exclude these subtypes. Many of the largest series use older pathologic classification schemes in which so-called "fibrosarcomas" or "malignant fibrous histiocytomas" have not been re-categorized appropriately as either a more specific diagnosis such as leiomyosarcoma, undifferentiated pleomorphic sarcoma, or undifferentiated/unclassified sarcoma. (See "Clinical presentation, histopathology, diagnostic evaluation, and staging of soft tissue sarcoma", section on 'Histopathology'.)

Despite these variations and limitations in reporting, some generalizations can be made about the demographics of head and neck sarcomas and the histologic and anatomic makeup of these tumors:

●Approximately 30 percent of head and neck sarcomas occur in children, with the majority of these being RMS [3].

●The median age at diagnosis for all head and neck sarcomas is 50 to 54 years, when children are included, and 55 to 59 years when they are not [15].

●Different subtypes affect different age groups. As examples, RMS occurs predominantly in children (median age of about five to nine years [15]) while angiosarcomas most often arise in the older adult population [9].

●Most series report a slight male predominance [15].

●Any site within the head or neck can be a primary site for a sarcoma since connective tissue is ubiquitous. Primary site predominance is determined by histologic subtype and is discussed within the following sections.

Risk factors — Secondary radiation-related head and neck sarcomas are well described and account for several percent of head and neck sarcomas [6,7,16-18]. Other pathogenetic factors are similar to those for other soft tissue sarcomas. (See "Pathogenetic factors in soft tissue and bone sarcomas" and 'Angiosarcoma' below.)

CLINICAL PRESENTATION AND DIAGNOSTIC EVALUATION — Patients generally present with a palpable mass (especially in the neck), skin changes (especially on the scalp or face), or subsite-specific symptoms (eg, hoarseness with laryngeal primaries, dysphagia with oropharyngeal tumors, epistaxis, nasal obstruction, or cranial nerve deficits with skull base tumors) [1,10,14,19]. Specific presenting symptoms will be discussed according to histologic subtype below.

Diagnosis and staging — As with all patients with a suspected head and neck neoplasm, a complete examination of the head and neck, with particular attention to the cranial nerves, is essential. For most patients, magnetic resonance imaging (MRI) is the superior neuroimaging study. In many cases, computed tomography (CT) scanning complements MRI, and both are helpful in surgical planning, particularly for bone sarcomas. Models can now be made preoperatively from CT scans for expected bone defects, allowing reconstructive planning and preparation to begin preoperatively, thus increasing the efficiency of the intraoperative repair. (See "Bone sarcomas: Preoperative evaluation, histologic classification, and principles of surgical management", section on 'Preoperative evaluation'.)

Pretreatment evaluation should also include a directed metastatic workup, generally with a CT of the chest. A more extensive diagnostic workup (eg, CT of the brain, radionuclide bone scan, positron emission tomography [PET] scan) should generally be based upon symptoms and/or clinical suspicion [20]. Further details on the pretreatment evaluation of these patients, including those with parameningeal rhabdomyosarcoma (RMS), are discussed separately. (See "Clinical presentation, histopathology, diagnostic evaluation, and staging of soft tissue sarcoma", section on 'Radiographic studies' and "Rhabdomyosarcoma in childhood and adolescence: Clinical presentation, diagnostic evaluation, and staging", section on 'Initial diagnostic and staging evaluation'.)

The role of PET scanning and integrated PET/CT imaging in the staging workup for soft tissue sarcomas (including RMS) and bone sarcomas, including those arising in the head and neck, is not clearly defined. There is no consensus on the appropriate use of this imaging modality. (See "Rhabdomyosarcoma in childhood and adolescence: Clinical presentation, diagnostic evaluation, and staging", section on 'Metastatic workup' and "Clinical presentation, histopathology, diagnostic evaluation, and staging of soft tissue sarcoma", section on 'PET and PET/CT'.)

Guidelines from the National Comprehensive Cancer Network (NCCN) suggest a PET and/or bone scan in the diagnostic workup of a suspected osteosarcoma but not soft tissue sarcoma [20]. Imaging guidelines from the Children's Oncology Group Bone Tumor Committee recommend radionuclide bone scan and/or PET scan for whole body staging for all patients with osteosarcoma [21]. Regardless of the type of scan that is chosen, the same imaging modality should be used throughout treatment and during posttreatment surveillance. Ideally, a PET scan or bone scan should be performed prior to biopsy to avoid a biopsy-related false positive result. (See "Osteosarcoma: Epidemiology, pathology, clinical presentation, and diagnosis", section on 'Postdiagnostic evaluation'.)

Performing a biopsy to obtain representative tissue for histologic evaluation is an important component of the initial evaluation. However, the biopsy method can affect subsequent treatment and thus should be carefully planned in conjunction with the surgeon who will perform the definitive surgery [22]. (See "Bone tumors: Diagnosis and biopsy techniques" and "Clinical presentation, histopathology, diagnostic evaluation, and staging of soft tissue sarcoma", section on 'Biopsy'.)

Staging systems

Soft tissue tumors — A modified version of the tumor, node, metastasis (TNM) staging system for head and neck squamous cell cancers is used in the eighth edition of the joint American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) staging of head and neck sarcomas. (See "Overview of the diagnosis and staging of head and neck cancer", section on 'TNM staging system'.)

In the eighth edition of the joint AJCC/UICC TNM staging system, the T staging for head and neck soft tissue sarcomas differs from that of sarcomas arising at other body sites (table 1) [23], and there are no prognostic stage groups [24].

This staging system is used for all soft tissue sarcomas of the head and neck, with the exception of angiosarcomas, embryonal and alveolar rhabdomyosarcoma, and Kaposi sarcoma (which do not have an AJCC staging system). (See "Clinical presentation, histopathology, diagnostic evaluation, and staging of soft tissue sarcoma", section on 'Introduction' and "Rhabdomyosarcoma in childhood and adolescence: Clinical presentation, diagnostic evaluation, and staging", section on 'Staging and prognostic stratification' and "Classic Kaposi sarcoma: Clinical features, staging, diagnosis, and treatment", section on 'Diagnosis and staging'.)

Bone sarcomas — There is a TNM staging system for bone sarcomas in the AJCC/UICC cancer staging manual; however, it has not been widely adopted in the past. The eighth edition AJCC staging system classifies bone sarcomas arising in the skull and facial bones the same way as it classifies tumors arising in the appendicular skeleton and trunk, and there is a set of prognostic stage groups (table 2) [25]. It remains to be seen whether this version will be widely adopted for clinical use.

NATURAL HISTORY AND PROGNOSTIC FACTORS — In general, the natural history of head and neck sarcomas parallels that of their non-head and neck counterparts, but with a higher rate of local recurrence after treatment. Whether overall survival rates are lower with head and neck primaries is unclear; the available data are conflicting.

Comparative outcomes for head and neck primary sarcomas can be illustrated by a single institution series comparing outcomes among 102 patients with head and neck sarcoma and 1044 patients with extremity or superficial trunk lesions, all of whom were treated between 1960 and 1999 with surgery and radiation therapy (RT) [26]. At five years, local control rates were inferior for patients with head and neck primaries (74 versus 85 percent) as was disease-specific survival (64 versus 76 percent). On the other hand, a separate study that used Surveillance, Epidemiology, and End Results (SEER) data on over 12,000 patients treated between 1973 and 2010 found a five-year cause-specific survival of 66 percent in adults and 73 percent in children with a broad variety of histologic subtypes, and these numbers appear comparable to those of non-head and neck sarcomas [15].

It is not clear that a primary site in the head and neck constitutes an independent risk factor for a worse prognosis per se. Rather, the complex functional anatomy of the head and neck makes it much harder to perform a resection with wide, negative margins. The failure to obtain negative margins is associated with a very poor prognosis. (See 'Surgical margins' below.)

As with soft tissue sarcomas in the extremities, lymph node involvement is uncommon, occurring in only about 10 percent of patients [27]. The most common histologic head and neck subtypes associated with nodal metastases are rhabdomyosarcoma (RMS) and angiosarcoma. (See "Clinical presentation, histopathology, diagnostic evaluation, and staging of soft tissue sarcoma", section on 'Regional nodes'.)

The majority of patients who die of soft tissue sarcomas in non-head and neck sites die of metastatic disease. In comparison, those with head and neck sarcomas frequently have local relapse and succumb to their tumor without distant metastatic disease. As an example, in a report of 103 patients with sarcoma of the head and neck treated from 1944 to 1988, locally recurrent disease was the sole cause of death in 65 percent [6]. The predominance of local recurrence occurs despite a relatively small average size (4 cm) compared with soft tissue sarcomas in other sites [4,7]. A major contributor is the difficulty in achieving clear surgical margins. (See 'Surgical margins' below and 'Surgical principles' below.)

Prognostic factors — Important prognostic factors are sex, tumor grade and size, status of the surgical margins, histologic subtype, and nodal status [6,7,15,28,29]. A large study of over 12,000 patients from the SEER database (which did not uniformly include data on grade, size, or margins) identified male sex, more advanced tumor stage, and treatment prior to year 2000 as adverse prognostic factors in multivariate analysis.

Histologic grade and tumor size — In most series, prognosis is worse in patients with higher grade (table 3) [30] and larger size tumors. In one study of 122 sarcomas of the head or neck, patients with high-grade lesions had significantly worse survival compared with those with low-grade lesions (hazard ratio [HR] for death 5.52, 95% CI 1.51-20.21), and locoregional recurrence rates were much higher for lesions >10 cm in diameter compared with tumors ≤5 cm (HR 6.13, 95%CI 1.84-20.5) [27].

Surgical margins — Negative margins are difficult to achieve in the region of the head and neck because these sarcomas tend to grow in tight anatomic confines and in close proximity to vital neurovascular, bony, or other structures. (See 'Surgical principles' below.)

Positive surgical margins are associated with a poor prognosis [4,6,7,10,19,29]. In a series of 146 patients with a variety of skull base sarcomas (both of soft tissue and bone), five-year disease-specific survival rates were 77, 43, and 36 percent for those with negative, close (often defined as <1 mm), and positive surgical margins, respectively [19]. The presence of positive/close margins was the only independent predictor of poor survival in multivariate analysis.

Histologic subtype — The influence of histologic subtype on prognosis was addressed in a report from the Head and Neck Sarcoma registry of the Society of Head and Neck Surgeons, which reported the results of treatment in 214 patients with sarcoma of the head or neck (194 adults and 20 children) [4]. Overall disease-free survival was 56 percent at five years. Major determinants of survival were adequacy of resection margins and tumor type (tumor grade was not available).

The biology of specific sarcoma histologies from other anatomic sites is recapitulated in the survival outcomes of patients with head and neck sarcomas with those similar histologies. For example, patients with sarcomas of the head and neck that do not metastasize (eg, chondrosarcoma or dermatofibrosarcoma protuberans [DFSP]) often have good outcomes, with survival approaching 100 percent. By contrast, patients with malignant fibrous histiocytoma (MFH) or fibrosarcoma (which usually comprise what is often termed undifferentiated pleomorphic sarcoma) of the head and neck had survival rates of 60 to 70 percent. Patients with diagnoses known to frequently metastasize when arising at other sites also fared poorly when the primary sites were head and neck; osteosarcoma and angiosarcoma had the worst survival, less than 50 percent at five years.

RMS and malignant peripheral nerve sheath tumor (MPNST) are particularly aggressive histologic subtypes [7,9,10,31]. Prior to modern chemotherapy, RMS was rarely cured. However, using modern combined modality treatment approaches, RMS is curable in over 75 percent of children. Those pediatric patients with unresected parameningeal tumors and high-risk features such as intracranial extension can experience a four-year failure-free survival of 68 percent, yet patients with unresected orbital locations have a 97 percent overall survival at three years using a reduced chemotherapy regimen [32,33]. It is worth noting that outcomes in adults with any RMS diagnosis are worse on average than outcomes in their pediatric counterparts. Treatment of RMS is addressed in detail separately. (See "Rhabdomyosarcoma in childhood, adolescence, and adulthood: Treatment".)

Nodal metastases — The presence of nodal metastases worsens prognosis in patients with RMS [34,35]. However, the impact of nodal metastases among patients with other soft tissue sarcomas of the head and neck is unclear; the available data are conflicting [10,36,37].

Radiation-associated sarcomas — Historically, sarcomas arising in tissues that have been previously irradiated have had a poorer prognosis when compared with de novo sarcomas [18,38,39]. (See "Radiation-associated sarcomas", section on 'Prognosis and treatment'.)

There are several potential reasons for these poor outcomes. Examples include delay in diagnosis; limitations on resectability due to prior surgery, radiation and fibrosis, and/or the size and location of the lesion (with an inability to achieve wide surgical margins); the high-grade nature of most radiation-associated sarcomas; inability to give full-dose RT to a site that has been previously irradiated; use of prior chemotherapy for the first cancer that may limit choices for subsequent therapy; and biologic differences that may reflect the different pathogenesis compared with spontaneously arising sarcomas, some of which are characterized by specific mutations. (See "Pathogenetic factors in soft tissue and bone sarcomas".)

Although the majority of prior studies suggest postirradiation sarcomas have a poorer prognosis, at least one small study specific to head and neck sarcoma (mostly post-nasopharyngeal cancer irradiation) supports the view that patients who can be treated with curative intent may have outcomes that are similar to those for de novo head and neck sarcomas, emphasizing the curative intent approach when possible [18].

GENERAL TREATMENT PRINCIPLES

Surgical principles — Because of their proximity to vital structures and the anatomic constraints within the head and neck region, surgical removal of head and neck sarcomas often cannot achieve the ideal "wide" resection margins that are preferred in other anatomic sites such as the extremities. Other important considerations include the functional deficits related to breathing, swallowing, and speaking, as well as the aesthetic outcomes that may follow head and neck resections. The anatomic boundaries forming the margin are considered a more important indicator of the risk for local recurrence than is the physical distance from the tumor to the resection margin [40]. Thus, the generally accepted recommendation for surgical margins of head and neck sarcomas is to obtain a complete tumor resection with as wide a margin as is feasible, with as little morbidity as possible.

The incidence of cervical lymph node metastases is sufficiently low in head and neck sarcomas that elective neck dissections are generally not indicated. However, a limited regional node dissection should be completed if vascular access is needed for free flap reconstruction. (See "Clinical presentation, histopathology, diagnostic evaluation, and staging of soft tissue sarcoma", section on 'Regional nodes'.)

As with head and neck squamous cell carcinomas, reconstruction with microvascular free flaps has greatly decreased the cosmetic deformity and improved functional results following resection of head and neck sarcomas. Large bone and soft tissue deficits that were once devastating can now be reconstructed with excellent results. (See "Mandibular and palatal reconstruction in patients with head and neck cancer" and "Management of acquired maxillary and hard palate defects".)

The benefits of a multidisciplinary approach to surgical and postsurgical treatment cannot be overemphasized. Input from a head and neck oncologic surgeon, radiation oncologist, medical oncologist, reconstructive surgeon, speech pathologist, and dietician are essential for an optimal surgical result. (See "Speech and swallowing rehabilitation of the patient with head and neck cancer".)

Adjuvant RT — When adjuvant radiation therapy (RT) is used for head and neck sarcomas, it is usually administered postoperatively and not prior to an operation, as is commonly done in extremity sarcomas. (See "Overview of multimodality treatment for primary soft tissue sarcoma of the extremities and superficial trunk", section on 'Choosing between preoperative and postoperative RT'.)

The benefit of adjuvant RT for most histologic subtypes is controversial. There are no randomized trials proving benefit for RT in head and neck sarcomas, and results from retrospective reports are mixed. However, extrapolation of experience in extremity sarcomas strongly argues in favor of adjuvant RT for most soft tissue sarcomas of the head and neck that are high grade (especially tumors that are large and high grade) or low grade with positive and/or close (often defined as <1 mm) margins. (See "Overview of multimodality treatment for primary soft tissue sarcoma of the extremities and superficial trunk", section on 'Radiation therapy'.)

In many studies, the addition of adjuvant RT to surgery for head and neck sarcomas does not provide a survival benefit compared with surgery alone. As an example, in a population-based analysis of 11,481 adult and 1244 pediatric head and neck sarcomas reported to the Surveillance, Epidemiology, and End Results (SEER) database between 1973 and 2010, the addition of RT resulted in an 80 percent reduction in survival compared with patients who did not receive adjuvant RT [15]. However, this outcome is at least partly the result of negative selection bias (ie, that use of RT is simply a marker for clinically appreciated, higher risk, poorer prognosis disease). To address this issue, the authors of the SEER analysis performed a propensity score-matched analysis and did not confirm an inferior cause-specific mortality in those who received adjuvant RT in conjunction with surgery. A lack of association of adjuvant RT with inferior cause-specific survival was also seen in a separate single institution series from the University of Washington [41].

On the other hand, retrospective series suggest a benefit for adding adjuvant RT to surgery in patients with soft tissue sarcomas of the head and neck, particularly if they are large and high-grade, or low-grade with positive and/or close margins [42], similar to the approach used with extremity sarcomas. As an example, in an observational analysis from the National Cancer Database of 1142 patients with head and neck sarcoma with positive surgical margins, the addition of adjuvant RT was associated with improved overall survival (57 versus 48 percent). However, this study also noted an underutilization of adjuvant RT in patients who had positive margins [43]. (See "Overview of multimodality treatment for primary soft tissue sarcoma of the extremities and superficial trunk", section on 'Radiation therapy'.)

The role of adjuvant RT for the individual sarcoma subtypes is discussed below.

Adjuvant chemotherapy — The benefits of adjuvant chemotherapy are highly dependent on histologic subtype and discussed in detail below.

CLINICAL FEATURES AND MANAGEMENT BY HISTOLOGIC SUBTYPE — The clinical presentation, prognosis, and management of specific histologic tumor types are discussed below.

Osteosarcoma — Osteosarcomas are primary malignant tumors of bone that are characterized by the production of osteoid or immature bone by the malignant cells. Osteosarcoma is the most common primary tumor of bone and about 10 percent of cases arise in the head and neck [44,45]. Only a little over 100 cases of head and neck osteosarcoma are diagnosed annually in the United States [44,46].

There is a slight male predominance [44,46]. The median age at presentation, 36, is at least 10 years older than patients with non-head and neck osteosarcomas, although for non-head and neck osteosarcomas, there is a second peak in incidence in later adulthood that corresponds to secondary Paget disease-related osteosarcoma [46-48]. (See "Osteosarcoma: Epidemiology, pathology, clinical presentation, and diagnosis", section on 'Epidemiology'.)

Clinical presentation — Osteosarcomas of the head and neck most commonly arise in the upper and lower jaws. The typical patient presents with a mass or swelling in the cheek or jaw, sometimes with pain, and occasionally with dental complaints [44,46-49]. In most series, the majority of tumors are about evenly split between the mandible and the maxilla; about 20 percent develop in the extragnathic bones (eg, skull, orbit) [17,50].

Head and neck osteosarcomas are typically smaller at presentation than are non-head and neck osteosarcomas, and they tend to be of a histologic lower grade than osteosarcomas at other sites (although most are high-grade) [44,51,52]. Plain radiographs demonstrate bony destruction with lytic, sclerotic, or mixed lesions, and indistinct margins [47].

Another difference is the incidence of lung metastases at diagnosis. While patients with extremity osteosarcoma are at very high risk for metastatic involvement of the lungs, lung metastases are less common in patients with jaw osteosarcomas [17,53,54]. (See "Osteosarcoma: Epidemiology, pathology, clinical presentation, and diagnosis", section on 'Clinical presentation'.)

Natural history and prognosis — Surgical accessibility plays a significant role in outcome of head and neck osteosarcomas as patients who are able to undergo complete or wide excision have a better prognosis [52,54-57]. As an example, patients with mandibular and maxillary tumors have better survival than do those with disease in the paranasal sinuses or calvarial bones [55].

Older series of patients with head and neck osteosarcoma reported five-year survival rates of approximately 40 percent [46,48,49,51,58-62]. However, improved outcomes have been seen over time, attributed in part to the introduction of modern multimodality management, which usually includes systemic chemotherapy [14,53,54,63]. As examples:

●One contemporary series of 44 patients, 30 of whom received neoadjuvant chemotherapy, reported three-year overall, disease-specific, and recurrence-free survival rates of 81, 81, and 73 percent, respectively [56]. Local control was achieved in 78 percent, a marked improvement over historical series, in which 50 to 65 percent of patients recurred.

●A retrospective analysis included 541 patients identified from the Surveillance, Epidemiology, and End Results (SEER) database from 1973 to 2011 using site-specific codes and histologic classification [52]. Importantly, the SEER database does not allow assessment of use of chemotherapy or status of margins. Overall survival and disease-free survival at 5 years were 53 percent and 62 percent, respectively, and at 10 years 35 percent and 54 percent, respectively. The magnitude of the difference between disease-free and overall survival in this very young population points to possibly significant late treatment-related mortality.

Local recurrence predominates as a pattern of failure for head and neck osteosarcomas; distant metastases are less common. As an example, in a meta-analysis that included 163 patients with head and neck osteosarcoma from nonrandomized studies, 56 percent recurred; of these, 50 percent recurred locally, 3 percent regionally, and only 20 percent had a component of distant failure [46]. Other series report somewhat higher rates of distant metastasis (35 to 50 percent [47,48]).

Local recurrences are usually, although not uniformly, fatal. These patients can occasionally be salvaged surgically if wide surgical margins can be attained [58,59].

Treatment (resectable disease) — The rarity of head and neck osteosarcoma and the lack of prospective trials make it difficult to reach valid conclusions regarding optimal treatment. Our approach to management is as follows:

●Initial treatment typically consists of en bloc excision of the tumor with a wide margin of normal tissue, if feasible. For patients who undergo initial resection with positive surgical margins, we prefer re-excision, if possible. (See 'Surgery' below.)

●For those with positive margins after re-excision or if re-excision is not feasible, we suggest postoperative (adjuvant) radiation therapy (RT). Some experts alternatively offer chemoradiation, typically with cisplatin as a radiosensitizer, extrapolating from the treatment approach used for squamous cell carcinoma of the head and neck. However, since there are limited prospective data to support the use of chemoradiation in head and neck sarcomas, and the optimal chemosensitizer is not established, the decision to use adjuvant RT alone or concurrently with chemotherapy should be made in a multidisciplinary setting. (See 'Radiation therapy' below and "Locally advanced squamous cell carcinoma of the head and neck: Approaches combining chemotherapy and radiation therapy", section on 'Concurrent chemotherapy'.)

●For patients with negative resection margins, we suggest not pursuing adjuvant RT. However, the decision to pursue RT for patients with margin-negative resections and other high-risk features such as very large tumor size, extensive soft tissue infiltration or lymphovascular invasion must be individualized and made on a case-by-case basis. (See 'Radiation therapy' below.)

●For most patients with high-grade tumors, we suggest adjuvant chemotherapy using an aggressive cisplatin-based regimen as used for osteosarcomas arising at other sites. For most patients with low-grade tumors we generally suggest not pursuing adjuvant chemotherapy. (See 'Chemotherapy' below.)

Surgery — En bloc excision with a margin of normal tissue is the goal of surgical treatment; however, soft tissue margins may be difficult to obtain because of the proximity of critical structures. The soft tissue resection margin can be evaluated intraoperatively by frozen section analysis until either a negative margin is obtained or further resection is not feasible. However, the bony margins cannot be microscopically evaluated in this way, and only a gross estimate of the resection margins can be performed intraoperatively. If the permanent sections show a positive bone margin, this should be addressed surgically, if possible, with reresection of the margin soon after the initial procedure.

As with other head and neck sarcomas, reconstruction is often best accomplished with microvascular free flap reconstruction. Bony defects can be reconstructed with osteocutaneous free flaps. Dental rehabilitation may be possible after healing is complete. Reconstruction of midface and skull base tumors may require either locoregional flaps for smaller defects or microvascular free flaps for larger defects. Maxillofacial prosthetics may also be necessary. (See "Mandibular and palatal reconstruction in patients with head and neck cancer" and "Management of acquired maxillary and hard palate defects".)

Radiation therapy — The importance of achieving clear surgical margins has been consistently demonstrated [54-56]. Following initial en bloc excision of the tumor with a sufficiently wide margin of normal tissue, we do not generally administer adjuvant RT if the surgical margins are clear. If the margin is positive, re-excision should be performed if possible [50].

For patients who are not candidates for re-excision or if the surgical margins remain positive after re-excision, we suggest adjuvant (postoperative) RT. Some experts alternatively offer chemoradiation, typically with concurrent cisplatin as a radiosensitizer [64-66], extrapolating from the treatment approach used for squamous cell carcinoma of the head and neck. However, since there are limited prospective data to support the use of chemoradiation in head and neck sarcomas, and the optimal chemotherapy regimen to use for radiosensitization is not established, this decision to use adjuvant RT alone or concurrently with chemotherapy should be made in a multidisciplinary setting. If both adjuvant chemotherapy and RT are being used, we would generally delay RT until the end of adjuvant chemotherapy. (See "Locally advanced squamous cell carcinoma of the head and neck: Approaches combining chemotherapy and radiation therapy", section on 'Concurrent chemotherapy'.)

Conventional osteosarcoma is relatively resistant to RT, although the small cell variant may be more radiosensitive. Primary RT is usually inadequate to achieve local control, particularly for bulky tumors [52]; surgery is preferred if possible.

For patients treated with effective surgery and chemotherapy, adjuvant RT does not improve survival and increases the risk for secondary tumors. However, local failure is a major cause of morbidity and death in head and neck osteosarcoma, and RT can help provide local control for patients in whom surgical resection with widely negative margins is not possible [50,55,60,67]. For patients with margin-negative resections but other high-risk features (large tumor size, extensive soft tissue infiltration, extensive lymphovascular invasion), the role of RT is not established, and the decision to pursue RT must be individualized and made on a case-by-case basis [52]. Rates of both acute and late RT complications are high (near 50 percent at 10 years), so use of RT should be limited to high-risk groups.

Proton beam RT may be particularly useful to treat osteosarcomas that involve the skull base [68]. (See "Chemotherapy and radiation therapy in the management of osteosarcoma", section on 'Radiation therapy'.)

Chemotherapy — For most patients with resected high-grade head and neck osteosarcomas, we suggest adjuvant chemotherapy using an aggressive cisplatin-based regimen as used for osteosarcomas arising at other sites. For most patients with low-grade tumors, we suggest not pursuing adjuvant chemotherapy. The decision to pursue chemotherapy for very small high-grade tumors and for very large low-grade tumors must be individualized and made on a case-by-case basis.

Modern treatment regimens for osteosarcomas at non-head and neck sites generally include systemic cisplatin-based chemotherapy to eradicate occult micrometastatic disease. While chemotherapy (given postoperatively [adjuvant] or preoperatively [neoadjuvant]) improves the prognosis of extremity osteosarcoma dramatically, its benefit in osteosarcoma of the head and neck is controversial. (See "Chemotherapy and radiation therapy in the management of osteosarcoma", section on 'Neoadjuvant versus adjuvant chemotherapy'.)

Prospective data to support benefit from adjuvant chemotherapy in head and neck osteosarcomas are lacking. In uncontrolled case series, the use of adjuvant or neoadjuvant chemotherapy has been associated with improved survival in patients with head and neck osteosarcomas in some [17,55,69-72] but not all [55,63] series. Two meta-analyses on this subject reported conflicting conclusions [46,73]. Part of the explanation for these disparate results may have been related to incomplete information on the influence of surgical margin status. Nevertheless, in many series, the majority of patients with high-grade osteosarcomas of the head and neck have received modern combination chemotherapy, and the improved outcomes over time have been largely attributed to the use of combined modality therapy. Whether it is optimal to deliver in the preoperative or postoperative setting is unclear. (see 'Natural history and prognosis' above)

Whether patients with low-grade osteosarcomas benefit from chemotherapy is unclear. Most low-grade jaw osteosarcomas may be adequately treated with surgery alone, as long as clear margins can be achieved [53]. Larger low-grade osteosarcomas, with poorer prognosis [69], may also benefit from chemotherapy, but the decision to pursue chemotherapy in these situations must be individualized and made on a case-by-case basis.

Treatment (unresectable or metastatic disease) — The treatment approach to unresectable or metastatic osteosarcoma of the head and neck is similar to that of osteosarcomas arising from other sites and is discussed separately. (See "Chemotherapy and radiation therapy in the management of osteosarcoma", section on 'Patients with metastatic disease at diagnosis'.)

Chondrosarcoma — Chondrosarcomas are a heterogeneous group of malignant bone tumors that share in common the production of chondroid (cartilaginous) matrix. Chondrosarcomas of the head and neck are rarer than osteosarcomas. The head and neck region is reported as the site of origin in 1 to 12 percent of chondrosarcomas [74-76]. Male individuals are affected three times more often than female individuals [77].

Clinical presentation — Chondrosarcomas present more commonly in the extragnathic bones than in the mandible or maxilla, in contrast with osteosarcomas. In a National Cancer Database series of 400 chondrosarcomas of the head and neck diagnosed between 1985 and 1995, 60 percent arose in bone, but only 7 percent of these were in the mandible [78].

Although chondrosarcomas less frequently develop in cartilage, it is the most common sarcoma that develops in the laryngeal cartilage; this site accounted for 19 percent of cases in one SEER series of 682 chondrosarcomas arising in the head and neck [79]. Approximately two-thirds of laryngeal chondrosarcomas originate in the cricoid cartilage [80,81].

Histology — Chondrosarcomas are classified according to microscopic appearance. In the report of the National Cancer Data Base of 400 cases, histologic subtypes included conventional (81 percent), myxoid (11 percent), and mesenchymal (9 percent) [78]. The mesenchymal and myxoid subtypes were rare among White patients (17 percent) and more common among African American patients and Hispanic American patients (32 and 45 percent, respectively). Histologic classification and grading of chondrosarcomas is discussed in detail elsewhere. (See "Chondrosarcoma", section on 'Classification, histology, and clinical features'.)

Treatment — The majority of chondrosarcomas are low grade, and long-term survival or cure is achieved with wide local excision in most patients. Laryngeal chondrosarcomas may be amenable to complete excision with preserved laryngeal function through a voice-sparing partial laryngectomy. For the rare patient with a dedifferentiated chondrosarcoma or possibly mesenchymal chondrosarcoma of the head and neck who is medically fit, the poor prognosis seen with surgery alone provides an argument to discuss the potential benefits of neoadjuvant or adjuvant doxorubicin-based chemotherapy. However, the efficacy of adjuvant chemotherapy in chondrosarcoma is overall limited given the general lack of sensitivity to chemotherapy seen with this histology.

Resectable disease

●Surgery – Treatment usually consists of wide local excision. The specific anatomic location of chondrosarcomas greatly affects resectability. For example, skull base chondrosarcomas are typically removed en bloc using advanced neurosurgical approaches. Such radical procedures may require sacrifice of multiple cranial nerves and necessitate carotid artery occlusion, with its attendant risk of death, stroke, and other significant morbidities. Management of skull base chondrosarcomas is discussed in detail elsewhere. (See "Chordoma and chondrosarcoma of the skull base".)

By contrast, chondrosarcomas of the larynx may be excised completely while preserving laryngeal function through a voice-sparing partial laryngectomy [82]. Local recurrences following organ preserving surgery usually require salvage laryngectomy and postoperative RT.

The majority of head and neck chondrosarcomas (with the exception of the mesenchymal subtype) are low grade and stage I [79], and long-term survival or cure is achieved with aggressive surgery in most patients. By contrast, high-grade tumors such as mesenchymal chondrosarcoma have a poorer prognosis. In the National Cancer Data Base series, in which 60 percent of patients were treated with surgery alone, and 21 percent received surgery plus RT, the overall disease-free survival for all subtypes at 5 and 10 years was 87 and 71 percent, respectively [78]. The myxoid and mesenchymal subtypes had a worse five-year disease-free survival (45 and 53 percent, respectively), as did those with higher grade tumors (67 percent).

Other reports note a low (approximately 20 percent [83-85]) survival for high-grade tumors, largely as a result of distant metastases. In at least one of these series, suboptimal resection may have contributed to the poor outcome; complete resection was only accomplished in one of seven patients with high-grade histology compared with 9 of 10 with low-grade histology [83].

●Chemotherapy – Experience with adjuvant (or neoadjuvant) chemotherapy in patients with mesenchymal chondrosarcoma suggests the potential for benefit. As an example, one retrospective study of 113 patients with mesenchymal chondrosarcomas included a subset of 96 patients with localized disease. Among this subset, chemotherapy was associated with a 57 percent improvement in survival and 52 percent improvement in local control [86]. However, these findings have not been prospectively confirmed, since there are no randomized studies evaluating effective adjuvant chemotherapy in patients with head and neck chondrosarcomas. Nevertheless, the poor prognosis seen with surgery alone provides an argument to discuss the risks and potential benefits of adjuvant doxorubicin-based chemotherapy with patients with mesenchymal chondrosarcoma who have not received neoadjuvant therapy as long as they are medically fit and able to tolerate the therapy. (See "Chondrosarcoma", section on 'Mesenchymal chondrosarcoma'.)

Unresectable disease — Unresectable chondrosarcomas (ie, those arising in the cervical spine or base of skull) can be treated with RT, especially proton beam RT. (See "Chordoma and chondrosarcoma of the skull base", section on 'Radiation therapy'.)

Rhabdomyosarcoma — Rhabdomyosarcoma (RMS) is predominantly a disease of children; 35 to 40 percent of primary sites are in the head and neck. However, cases of RMS are reported in adults at all sites, including the head and neck [87-89]. In a report from the National Cancer Institute (NCI) SEER database, 35 percent of head and neck RMS reported between 1973 and 2005 arose in patients 19 years of age or older [15].

Clinical presentation — The clinical presentation is dependent upon tumor location and may include a facial or neck mass, proptosis, nasal discharge, headache, vomiting, change in hearing, vision, speech, swallowing, or respiratory symptoms. (See "Rhabdomyosarcoma in childhood and adolescence: Clinical presentation, diagnostic evaluation, and staging", section on 'Head and neck'.)

The sites of head and neck RMS can be divided into three main groups: orbit (25 percent), parameningeal area (paranasal sinuses, nasopharynx, nasal cavity, middle ear/mastoid, and infratemporal fossa; 50 percent), and nonorbital nonparameningeal sites (scalp, parotid gland, oral cavity, pharynx, thyroid and parathyroid glands, and neck; 25 percent).

Histology — The two major histologic subtypes of RMS are embryonal and alveolar, although classification and risk stratification rely on the presence or absence or the characteristic PAX/FOXO1 fusion gene (table 4). When head and neck RMS arises in the orbit, it is almost always of the embryonal type. A unique form of embryonal RMS, the botryoid variant (sarcoma botryoides), typically arises within the wall of the bladder or vagina, almost exclusively in infants. However, it can arise within the nasopharynx in older children. (See "Rhabdomyosarcoma in childhood and adolescence: Epidemiology, pathology, and molecular pathogenesis", section on 'Histologic classification'.)

Staging and prognostic stratification — The initial radiologic evaluation should include computed tomography (CT) scan or magnetic resonance imaging (MRI) of the primary site and surrounding structures [90]. MRI is increasingly considered the imaging method of choice for certain primary locations, such as the head and neck, because of its multiplanar capacity, ability to attenuate bone artifact, and superior soft tissue contrast. While CT scan may best identify lung metastases, MRI or integrated positron emission tomography (PET)/CT scans efficiently evaluate bone, soft tissue, and parenchymal organs. Distant brain metastases are uncommon. In general, brain imaging is reserved for patients with clinical suspicion; however, imaging of the brain is often included as part of the imaging of the primary site, especially in parameningeal tumors. Since parameningeal tumors may show earlier spread to the skull base and the intracranial compartment, lumbar puncture should be performed. (See "Rhabdomyosarcoma in childhood and adolescence: Clinical presentation, diagnostic evaluation, and staging", section on 'Lumbar puncture'.)

Two different staging systems are used in conjunction by the Intergroup Rhabdomyosarcoma Study Group (IRSG)/Children's Oncology Group (COG) for the purpose of estimating prognosis and assigning risk-directed treatment. The IRSG Clinical Group (CG) system recognizes four disease categories (Group I through IV) that are based upon the degree of tumor spread at diagnosis and the amount of disease remaining after initial surgery (table 5).

Although the CG system is clinically useful for assigning treatment, it does not take into account other important prognostic factors, such as tumor size and primary site, disease extent, histology, and patient age. A site-based tumor-node-metastasis (TNM) staging system was incorporated for assessing prognosis and assigning therapy in conjunction with the traditional surgicopathologic clinical grouping system (table 6). Although there are clear prognostic differences based upon the site of origin, within the head and neck, prognosis is more specifically dependent upon location than TNM stage and upon other factors such as age and histologic type.

Both the CG and TNM stage as well as several other clinicopathologic variables are included in a prognostic stratification system that is used to select treatment based upon the estimated prognosis (risk-adapted therapy (table 4)). RMS of the orbit and eyelid are considered favorable prognosis sites, while parameningeal tumors are considered unfavorable. (See "Rhabdomyosarcoma in childhood and adolescence: Clinical presentation, diagnostic evaluation, and staging".)

Prognosis — Prior to 1970, the outlook for children with RMS was dismal, with cure rates of 20 percent from surgery, with or without RT. Outcomes have markedly improved with the addition of systemic chemotherapy, including those for individuals with head and neck primary sites. Reported five-year survival rates with contemporary therapy are 50 to 75 percent for patients with nonmetastatic head and neck parameningeal disease, and 70 to 80 percent for patients with nonmetastatic, nonparameningeal head and neck disease sites [91,92]. (See "Rhabdomyosarcoma in childhood, adolescence, and adulthood: Treatment", section on 'Overview of IRSG study results'.)

Prognosis also depends upon the site of presentation and age:

●The influence of disease subsite was addressed in a SEER database review of 558 cases of head and neck RMS reported between 1973 and 2007 [93]. Five-year survival for orbital, nonorbital nonparameningeal, and parameningeal sites was 84, 70, and 49 percent, respectively.

●As a group, adults probably have a worse prognosis than do children with RMS [15,89,94-96]. In a review of the SEER database of 11,481 adult cases and 1244 pediatric cases of head and neck sarcoma diagnosed between 1973 and 2010, five-year disease-specific survival with RMS was 68 percent in the pediatric group compared with 36 percent in the adult cohort [15].

The poorer outcomes in adults may reflect, in part, the inadequacy of primary treatment. However, adults are also more likely to present with advanced disease. As an example, in one series of 26 adults with head and neck RMS, 69 percent were stage III or IV at presentation, and the five-year survival rate for all patients was 8 percent [94]. By contrast, in the IRSG studies, fewer than 15 percent of children had stage IV disease, and the cure rate with multimodality therapy was about 70 percent [91,97,98]. (See "Rhabdomyosarcoma in childhood, adolescence, and adulthood: Treatment", section on 'Treatment of adults'.)

A critical issue for the predominantly young patient with RMS, most of whom will survive the cancer, is late complications from therapy. For head and neck sites, this includes short stature or facial asymmetry in almost one-third of long-term survivors, poor dentition in one-fourth, and impaired vision, hearing, and learning, each in one-sixth of survivors [99]. (See "Rhabdomyosarcoma in childhood, adolescence, and adulthood: Treatment", section on 'Long-term complications'.)

Overview of treatment — The treatment of RMS is complex, and typically involves surgery, RT, and multi-agent chemotherapy. A consultation with a center with expertise in multimodality therapy for this rare diagnosis is appropriate; in many situations, children will be offered treatment on a clinical trial, since the standards of care for this diagnosis continue to evolve.

For most patients with localized disease, complete excision is offered as long as functional and/or cosmetic results are acceptable. Routine cervical lymph node dissection is not routinely recommended as part of the staging workup in patients with head and neck RMS, given the low incidence of locoregional lymph node involvement. However, for some anatomic locations, such as parameningeal sites, chemotherapy and radiation are the standard of care rather than surgical resection. When surgical excision is not possible, or when surgery is incomplete, RT is used for local control. Risk-adapted therapy guidelines assist in treatment decisions for adjuvant RT and adjuvant chemotherapy, including selection of the appropriate chemotherapy regimen. The results of five large IRSG treatment studies (IRS I-V), enrolling the majority of American children with RMS, have established many of the general principles that guide modern management of RMS. These are discussed in detail elsewhere. (See "Rhabdomyosarcoma in childhood, adolescence, and adulthood: Treatment", section on 'Overview of IRSG study results'.)

The following represent general principles of management for RMS of the head and neck:

●Complete excision is offered for localized disease as long as functional and/or cosmetic results are acceptable. However, primary head and neck tumors are rarely amenable to wide local excision because of proximity to vital structures and cosmetic concerns. The availability of highly skilled otolaryngologic and craniofacial reconstructive teams may permit resection of some tumors that would otherwise be considered unresectable. (See "Rhabdomyosarcoma in childhood, adolescence, and adulthood: Treatment", section on 'Head and neck'.)

●In addition, when surgical excision is not possible, or when surgery is incomplete, RT is used for local control, despite the significant risk of facial asymmetry in the growing skeleton.

●For some anatomic locations, such as parameningeal sites, chemotherapy and radiation are the standard of care rather than surgical resection.

●Because of the generally low incidence of locoregional lymph node involvement, routine cervical lymph node dissection is not routinely recommended as part of the staging work up in patients with head and neck RMS, including those in parameningeal sites. Confirmation with lymph node sampling is recommended only when clinical and/or imaging studies suggest lymph node involvement. (See "Rhabdomyosarcoma in childhood, adolescence, and adulthood: Treatment", section on 'Head and neck'.)

There is some concern that lymph node involvement might be underestimated with available guidelines, which suggest radiographic screening for evidence of suspicious lymphadenopathy [100]. In particular, some data suggest that patients with parameningeal primary sites and alveolar histology may be at a higher than expected risk for nodal dissemination, and that thorough staging of the retropharyngeal and cervical lymph nodes is necessary in this setting [101,102]. However, routine nodal dissection, even in these settings, is not widely accepted; this is a controversial area. (See "Rhabdomyosarcoma in childhood and adolescence: Clinical presentation, diagnostic evaluation, and staging", section on 'Regional nodes'.)

●The COG (into which IRSG was merged) has developed risk-adapted therapy guidelines to assist in treatment decisions for adjuvant RT and/or adjuvant chemotherapy, including selection of chemotherapy regimen (table 4).

Although RT for RMS is commonly delivered through external beam RT, for children with small, critically located tumors in the head and neck, intracavitary or interstitial implants (brachytherapy) may be an option [92,103]. Brachytherapy may allow dose intensification by delivering RT to a restricted tissue volume, with preservation of anatomy and organ function, and with decreased late effects by minimizing scatter to adjacent structures. Brachytherapy may also have a role in salvage treatment of recurrent disease.

●Adults with RMS should be treated in a manner analogous to children, with chemotherapy regimens adjusted appropriately. (See "Rhabdomyosarcoma in childhood, adolescence, and adulthood: Treatment", section on 'Treatment of adults'.)

A more detailed overview of the treatment of RMS is presented separately. (See "Rhabdomyosarcoma in childhood, adolescence, and adulthood: Treatment".)

Angiosarcoma — Angiosarcomas are aggressive tumors arising in either blood or lymphatic vessels. Angiosarcomas account for about 15 percent of all head and neck sarcomas and 1 percent of all soft tissue sarcomas [4,7,9]. The scalp and face are the most common sites of origin. In a SEER database series of 434 cases of cutaneous angiosarcomas reported between 1973 and 2007, 270 (72 percent) arose in the region of the head and neck [104].

Head and neck angiosarcomas tend to be a disease of older adults (median age of incidence of 65 to 70) of the male sex (male to female ratio of 2:1) [9,10,104-109].The relative predominance of angiosarcomas among the older, White population, and localization to the face and scalp has led some to propose that sun exposure contributes to the etiology, but this has not been clearly demonstrated. A prior history of RT to the face or scalp is elicited in 5 to 20 percent of patients [105,106,110].

Clinical presentation — Patients typically present with a blue or purple lesion on the scalp or face that has been present for several months [105-107]. These lesions may appear macular, nodular, or plaque-like. Diffuse, clinically undetectable intradermal spread leads to indistinct borders and a high incidence of multicentricity [111]. Advanced lesions can show hemorrhage or ulceration. Cervical lymphadenopathy is found in approximately 10 percent of patients at the time of presentation.

Natural history and prognosis — The outlook for these tumors is poor, with five-year survival generally less than 40 percent [104,105,108,112-115]. As an example, in a series of 133 angiosarcomas of the scalp and neck reported to the SEER database between 1973 and 2007, 5 and 10-year survival rates were 34 and 14 percent, respectively. The multifocal nature of angiosarcomas and local recurrences often complicate therapy, and distant metastases are also frequent [108,113,114].

The most important prognostic factor for survival in patients with head and neck angiosarcoma is size and the ability to completely resect the tumor [105-108,113,116]. Patients with tumors less than 5 cm in diameter have better overall survival and a lower risk of regional recurrence [105-107,116,117]. In addition, cellular epithelioid morphology is emerging as a potentially adverse prognostic factor [113], as is age 70 and older [115].

Treatment — There is limited evidence, other than case series, upon which to base treatment recommendations for angiosarcoma of the head and neck, and the optimal sequence of treatments associated with the best outcomes for this rare diagnosis has yet to be defined.

For patients with resectable disease, complete surgical resection with wide margins is preferred for local and locoregional disease, when technically feasible. For almost all patients who undergo resection, we suggest preoperative or postoperative RT due to the propensity of these tumors for insidious local infiltration, which can lead to locoregional and/or distant metastases. The role of adjuvant or neoadjuvant chemotherapy in patients with resectable disease is unclear, and we do not offer it routinely.

For patients with disease that is initially unresectable, neoadjuvant chemotherapy and/or RT is a reasonable approach that may allow some patients with locally advanced lesions to undergo potentially less mutilating surgery.

Resectable disease

●Surgery – Complete surgical resection with wide margins is preferred for local and locoregional disease. Although the risk of lymph node spread is higher with angiosarcomas than with other head and neck sarcomas, the overall risk remains lower than what is generally considered an indication for elective lymph node dissection. As a result, most surgeons reserve neck treatment for gross nodal disease only.

Reconstruction is performed immediately following resection; even sizable deficits can be reconstructed using contemporary techniques. Microvascular free flaps can cover large surface defects with minimal donor site morbidity. Smaller defects can be reconstructed using skin grafts, or local or regional flaps. Some surgeons perform small mapping biopsies along the proposed margins preoperatively so that disease with subclinical microscopic spread can be identified and appropriate ablative and reconstructive planning undertaken prior to definitive resection.

●Radiation therapy – Due to the propensity for insidious local infiltration, resection should be combined in nearly all cases by preoperative or postoperative RT. Although randomized trials are not available, the benefits of RT are supported by several small reports [105-107,111,115,117]. As examples:

•In one series of 28 patients with angiosarcoma of the head and neck treated at the University of California, Los Angeles (UCLA), only 1 of 12 patients treated with surgery alone remained disease free compared with four of six who received postoperative RT, with or without chemotherapy [106].

•In a subsequent report of 70 patients with nonmetastatic angiosarcoma of the face and scalp, combined therapy with surgery plus RT (versus surgery alone or RT alone) was associated with improved overall survival (68 versus 32 percent), disease-specific survival (76 versus 33 percent), as well as better local control [117].

●Adjuvant or neoadjuvant chemotherapy – The role of adjuvant chemotherapy, either alone or concurrent with RT, is unclear [118-120]. There are also limited data for the use of neoadjuvant chemotherapy in this setting. In a series of 70 patients with nonmetastatic angiosarcoma, the addition of any chemotherapy (either neoadjuvant or adjuvant) to local therapy was not associated with improved five-year overall survival (45 versus 39 percent) [117].

Unresectable disease — For patients with locally advanced, unresectable tumors or those who decline surgery, options include definitive RT, sequential chemotherapy and radiation, or combined chemoradiation, none of which has been proven superior to the others. There is also increasing interest in the use of neoadjuvant chemotherapy and/or RT as a component of combined modality therapy, which may allow some patients to undergo potentially less mutilating surgery, using induction chemotherapy for squamous cell head and neck cancer as a treatment model [113,121]. (See "Locally advanced squamous cell carcinoma of the head and neck: Approaches combining chemotherapy and radiation therapy".)

Metastatic disease — Systemic therapy for metastatic angiosarcoma of the head and neck is discussed separately. (See "Overview of the initial treatment of metastatic soft tissue sarcoma", section on 'Angiosarcoma' and "Second and later lines of therapy for metastatic soft tissue sarcoma", section on 'Angiosarcoma'.)

Desmoids and dermatofibrosarcoma protuberans — Desmoid tumors and dermatofibrosarcoma protuberans (DFSP) are both locally aggressive tumors that can involve the head and neck regions. Desmoid tumors and DFSP involves the head and neck region in between 10 and 25 percent of cases [122-124].

Desmoid tumors (also called aggressive fibromatosis) are benign, slowly growing neoplasms arising from fibroblastic stromal elements [125]. Although desmoid tumors are locally aggressive, with a propensity for local recurrence even after complete resection, they do not have the capacity to establish metastatic lesions. Nevertheless, desmoid tumors can be lethal, particularly in the abdominal cavity, and rarely in the head and neck area, due to their local invasive behavior. Multidisciplinary review of options for treatment is the recognized standard of care. (See "Desmoid tumors: Epidemiology, molecular pathogenesis, clinical presentation, diagnosis, and local therapy".)

DFSP is a low- to intermediate-grade cutaneous sarcoma characterized by a translocation involving chromosomes 17 and 20. It is most common in adults who are 20 to 30 years of age, although it has also been described in children. As with other sites, DFSP of the head and neck has a marked propensity for local recurrence but is typically associated with long-term survival [4,7,9]. Metastatic disease occurs in less than 6 percent of cases and is usually preceded by two or more local recurrences. (See "Dermatofibrosarcoma protuberans: Treatment", section on 'Prognosis'.)

Clinical presentation — DFSP often presents as a firm, solitary, slowly enlarging, cutaneous nodule between 2 and 5 cm in size. The scalp and neck (supraclavicular fossa) are the most common sites in the head and neck.

Histology — The fibrosarcomatous variant represents an uncommon form of DFSP that is associated with a significantly more aggressive clinical course. The Bednar variant of this tumor is even less common and is distinguished histologically by the dispersal of melanin-containing cells in an otherwise typical DFSP. (See "Dermatofibrosarcoma protuberans: Epidemiology, pathogenesis, clinical presentation, diagnosis, and staging", section on 'Diagnosis'.)

The histologic diagnosis of desmoid tumors is discussed separately. (See "Desmoid tumors: Epidemiology, molecular pathogenesis, clinical presentation, diagnosis, and local therapy", section on 'Histologic diagnosis'.)

Treatment

●Desmoid tumors – For patients with asymptomatic, stable desmoid tumors of the head and neck, an initial period of close observation is an acceptable strategy. Treatment may be initiated at the onset of symptomatic and/or progressive disease, if there is imminent risk to adjacent structures or if the tumor creates cosmetic concerns. Initial treatment may include surgery or systemic therapy alone. If observation is chosen, follow-up should be frequent to avoid substantial disease progression that can be associated with high morbidity. (See "Desmoid tumors: Systemic therapy", section on 'Hormonal therapy' and "Desmoid tumors: Systemic therapy", section on 'Cytotoxic chemotherapy' and "Desmoid tumors: Systemic therapy", section on 'Observation versus systemic therapy'.)

Treatment for resectable desmoid tumors of the head and neck involves complete excision with pathologically negative margins, when possible. Radiation (RT) is an option in recurrent, marginally resectable, or unresectable tumors; however, RT should be avoided in young patients due to the risk of late toxicities including radiation-associated cancers. Cryotherapy is used in some centers as an alternative to surgery for accessible lesions, either as initial or salvage therapy [126]. (See "Desmoid tumors: Epidemiology, molecular pathogenesis, clinical presentation, diagnosis, and local therapy", section on 'Treatment'.)

For patients with unresectable or recurrent desmoid tumors, options for initial systemic therapy include chemotherapy, hormonal therapy, or targeted agents. Sorafenib and other systemic therapies may provide significant value for unresectable, progressive, or recurrent desmoid tumors. In one phase III trial, sorafenib improved progression-free survival, with some durable responses [127]. Some studies also support the clinical benefit of imatinib in patients with indolent tumors who have failed or do not tolerate hormonal therapy or sorafenib. Data supporting the efficacy of these treatments are discussed separately. (See "Desmoid tumors: Systemic therapy", section on 'Tyrosine kinase inhibitors'.)

●Dermatofibrosarcoma protuberans – The preferred initial treatment for DFSP of the head and neck is resection with pathologically negative margins. As with DFSP at other sites, approximately 33 to 50 percent of patients experience local recurrence after local excision, often within three years [128]. Wide local excision (WLE) with 3 cm margins of visibly uninvolved tissue, when possible, and inclusion of superficial fascia produces better clearance rates, but with a corresponding loss of normal tissue. As at other sites, Mohs micrographic surgery of DFSPs arising in the head and neck has been shown to provide adequate local control while reducing local recurrence rates compared with WLE (1.11 versus 6.32 percent in one systematic review) [129], with a significant sparing of adjacent normal tissue, thus preserving cosmetically and functionally vital tissue [130-134]. (See "Dermatofibrosarcoma protuberans: Treatment", section on 'Mohs micrographic surgery'.)

Although DFSP is a somewhat radioresponsive tumor, we avoid RT as primary treatment. Although adjuvant RT may be recommended for patients with positive resection margins, especially after an initial recurrence, there is no consensus regarding the role of adjuvant RT for patients with completely resected disease since its benefit is limited to improved local control but not improved overall survival [135]. This may be one type of sarcoma where brachytherapy could be of particular use in avoiding toxicity of external beam radiation. (See "Dermatofibrosarcoma protuberans: Treatment", section on 'RT following surgical resection'.)

Data support the use of imatinib in DFSP for recurrent, unresectable, or metastatic disease. The majority of DFSPs has a translocation involving chromosomes 17 and 22, which places platelet-derived growth factor beta (PDGFB) under the control of the COL1A1 promoter, leading to constitutive activation of the PDGF receptor (PDGFR), a receptor tyrosine kinase. Orally active small molecule tyrosine kinase inhibitors such as imatinib inhibit the PDGFR. Imatinib is approved in the United States and Europe for use in adult patients who have unresectable, recurrent, and/or metastatic DFSP, either alone or in combination with surgery. (See "Dermatofibrosarcoma protuberans: Treatment", section on 'Imatinib'.)

Other adult soft tissue sarcomas — For other adult-type soft tissue sarcomas that do not fit into any of these categories, treatment principles for these tumors should follow those used for tumors outside of the head and neck region. Extirpative surgery with wide margins is preferred, if feasible. We recommend adjuvant RT (either preoperative or postoperative) for most high-grade tumors and any malignant tumor (even low-grade) treated with less than wide margin excisional surgery. The benefit of adjuvant chemotherapy following optimal local therapy remains uncertain. We do not routinely pursue this approach for soft tissue sarcomas arising in the head and neck; however, it may be an option for patients with a good performance status who are at high risk of a distant or possibly local recurrence.

Approximately 40 percent of all head and neck sarcomas do not fit into any of the above histologic categories. These include a variety of histologies (undifferentiated/unclassified sarcoma [previously called malignant fibrous histiocytoma (MFH)], malignant peripheral nerve sheath tumors [MPNST], synovial sarcoma, leiomyosarcoma [LMS], liposarcoma, etc) and they can arise from any site in the head and neck. In an analysis of 11,481 adult head and neck sarcomas using the SEER database, undifferentiated/unclassified sarcomas represented 38 percent of all head and neck sarcomas [15]. Unlike soft tissue sarcomas at other sites, those involving the head or neck more often cause death by local recurrence [6,136]. Synovial sarcomas involving sites in the head and neck are rare overall; they appear to behave more aggressively than those involving the extremities, and prognosis is generally less favorable [137-140].

Treatment principles for these tumors should ideally follow those used for tumors outside of the head and neck region:

●Extirpative surgery with wide margins should be employed when possible. Some suggest that a 2 cm margin is optimal [141], but this is not attainable at all anatomic sites.

●RT should be used to improve local control for most high-grade sarcomas and all with positive or close margins. The addition of RT does not provide significant improvement in disease-specific mortality as demonstrated in a SEER analysis of 11,481 adult sarcomas, but selection bias may account for the negative association [15]. Adjuvant RT provides improved local control in small series in cases of positive margins [42,142-145]. Although experience is limited, preoperative RT appears to be associated with fewer acute postoperative wound complications than in extremity sites and may permit lower doses of RT to be used while providing a high rate of local control [146]. (See "Overview of multimodality treatment for primary soft tissue sarcoma of the extremities and superficial trunk", section on 'Choosing between preoperative and postoperative RT'.)

●Unresectable tumors should be treated with RT [42]. More often, this will result in palliative benefit rather than cure.

●The role of adjuvant chemotherapy for head and neck sarcomas is unknown. For high-grade, large extremity sarcomas, the benefit of chemotherapy is controversial, and data from individual trials and meta-analyses suggest that a survival benefit, if it exists, is small. However, a meta-analysis suggests improved local control with adjuvant chemotherapy [147], which may be relevant for sarcomas that occur in the head and neck, for which local recurrence is the main cause of treatment failure. The discussion and decisions about adjuvant chemotherapy should be individualized but only take place with patients who have a good performance status. (See "Adjuvant and neoadjuvant chemotherapy for soft tissue sarcoma of the extremities" and "Overview of multimodality treatment for primary soft tissue sarcoma of the extremities and superficial trunk".)

●In the absence of demonstrable metastases, local recurrences should be treated aggressively, as they can occasionally be salvaged by further surgery [42,148].

●Systemic therapy for metastatic disease is addressed in detail elsewhere. (See "Overview of the initial treatment of metastatic soft tissue sarcoma".)

A postoperative nomogram for 12-year sarcoma-specific death has been proposed for patients with head and neck soft tissue sarcoma, but it has not yet been independently validated [149].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Soft tissue sarcoma" and "Society guideline links: Bone sarcomas".)

SUMMARY AND RECOMMENDATIONS

●Epidemiology and common histologies of head and neck sarcomas – Head and neck sarcomas are rare tumors, accounting for only about 2 percent of all head and neck malignancies and for 4 to 10 percent of all sarcomas. (See 'Epidemiology, histologic distribution, and risk factors' above.)

The most common head and neck sarcoma histologies include osteosarcoma, chondrosarcoma, rhabdomyosarcoma (RMS), angiosarcoma, desmoid tumors, and dermatofibrosarcoma protuberans (DFSP). (See 'Clinical features and management by histologic subtype' above.)

●Clinical presentation – Patients generally present with a palpable mass (especially in the neck), skin changes (especially on the scalp or face), or subsite-specific symptoms (eg, hoarseness with laryngeal primaries, dysphagia with oropharyngeal tumors, epistaxis, nasal obstruction, or cranial nerve deficits with skull base tumors). (See 'Clinical presentation and diagnostic evaluation' above.)

●Diagnosis and staging – For most patients suspected of having a head or neck sarcoma, magnetic resonance imaging (MRI) is the superior neuroimaging study, although in many cases, computed tomography (CT) scanning complements MRI, and both are helpful in surgical planning. Pretreatment evaluation should also include a directed metastatic workup. The diagnostic biopsy method should be carefully planned in conjunction with the surgeon who will perform the definitive surgery. (See 'Diagnosis and staging' above.)

●Natural history and prognostic factors – In general, the natural history of these tumors parallels that of their non-head and neck counterparts, but with a higher rate of local recurrence after treatment. Whether overall survival rates are lower with head and neck primaries is unclear; the available data are conflicting. The major prognostic factors are histologic grade, tumor size, status of the surgical margins, histologic subtype, and the presence of nodal metastases. (See 'Natural history and prognostic factors' above.)

●Surgical principles – The generally accepted recommendation for surgical margins of head and neck sarcomas is to obtain a complete tumor resection with as wide a cuff of normal tissue as is feasible, with as little morbidity as possible. Because of their proximity to vital structures and the relatively small space of the head and neck region, surgical removal of head and neck sarcomas often cannot achieve the ideal "wide" resection margins that are preferred in other anatomic sites, and there are important considerations for morbidity related to breathing, swallowing, and speaking, and the significant cosmetic deformity that may follow neck and facial resections. The generally accepted recommendation for surgical margins of head and neck sarcomas is to obtain a complete tumor resection with as wide a cuff of normal tissue as is feasible, with as little morbidity as possible. (See 'Surgical principles' above.)

●Adjuvant therapy – The benefit of adjuvant radiation therapy (RT) for most histologic subtypes is controversial. There are no randomized trials proving benefit for head and neck sarcomas. Extrapolation of experience in extremity sarcomas strongly argues in favor of adjuvant RT for most soft tissue sarcomas of the head and neck that are high grade (especially tumors are that are large and high grade), or low grade with positive and/or close margins. (See 'Adjuvant RT' above and "Overview of multimodality treatment for primary soft tissue sarcoma of the extremities and superficial trunk", section on 'Radiation therapy'.)

Adjuvant chemotherapy is an accepted component of standard therapy for large, high-grade or margin-positive osteosarcomas and for RMS. (See 'Chemotherapy' above and 'Overview of treatment' above.)

●Osteosarcoma – Osteosarcomas most commonly arise in the jaw. The typical patient presents with a mass or swelling in the cheek or jaw, sometimes with pain, and occasionally with dental complaints. (See 'Osteosarcoma' above.)

•Initial treatment should consist of en bloc excision of the tumor with a wide margin of normal tissue, if feasible. For patients who undergo initial resection with positive surgical margins, we prefer re-excision, if possible. (See 'Treatment (resectable disease)' above.)

•For patients with positive surgical margins after re-excision, or if re-excision is not feasible, we suggest adjuvant RT (Grade 2C). Some experts alternatively offer chemoradiation, typically with cisplatin as a radiosensitizer, extrapolating from the treatment approach used for squamous cell carcinoma of the head and neck. However, since there are limited prospective data to support the use of chemoradiation in head and neck sarcomas, and the optimal chemosensitizer is not established, the decision to use adjuvant RT alone or concurrently with chemotherapy should be made in a multidisciplinary setting.

•For most patients with negative resection margins, we suggest not pursuing adjuvant RT (Grade 2C). However, the decision to pursue RT for patients with margin-negative resections and other high-risk features such as very large tumor size, extensive soft tissue infiltration or lymphovascular invasion must be individualized and made on a case-by-case basis with multidisciplinary input. (See 'Radiation therapy' above.)

•For most patients with high-grade tumors, we suggest adjuvant chemotherapy using an aggressive cisplatin-based regimen as used for osteosarcomas arising at other sites (Grade 2B). (See "Chemotherapy and radiation therapy in the management of osteosarcoma", section on 'Principles of chemotherapy'.)

•For patients with low-grade osteosarcomas, we suggest not pursuing adjuvant chemotherapy (Grade 2C). The decision to pursue chemotherapy for very small high-grade tumors must be individualized and made on a case-by-case basis.

●Chondrosarcoma – Chondrosarcomas are more common in the extragnathic bones than in the mandible or maxilla, but a significant number develop from laryngeal cartilage. The majority are low grade, and long-term survival or cure is achieved with wide local excision in most patients. Laryngeal chondrosarcomas may be amenable to complete excision with preserved laryngeal function through a voice-sparing partial laryngectomy. (See 'Chondrosarcoma' above.)

•For the rare patient with a dedifferentiated chondrosarcoma or mesenchymal chondrosarcoma of the head and neck who is medically fit, the poor prognosis seen with surgery alone provides a rationale to offer neoadjuvant or adjuvant doxorubicin-based chemotherapy. (See "Chondrosarcoma", section on 'Mesenchymal chondrosarcoma'.)

•Unresectable chondrosarcomas (eg, those arising at the skull base or upper cervical spine) should be treated with RT, with proton beam RT having advantages over photon-based approaches. (See "Chordoma and chondrosarcoma of the skull base", section on 'Radiation therapy'.)

●Rhabdomyosarcoma – RMS is predominantly a disease of children; 35 to 40 percent of primary sites are in the head and neck. The clinical presentation is dependent upon tumor location and may include a facial or neck mass, proptosis, nasal discharge, headache, vomiting, change in hearing, vision, speech, swallowing, or respiratory symptoms. (See 'Rhabdomyosarcoma' above.)

•The treatment of RMS is complex, and typically involves surgery, RT, and multi-agent chemotherapy. Multidisciplinary management is the standard of care. If appropriate, children should be offered treatment on a clinical trial. (See 'Overview of treatment' above.)

•For most patients with localized disease, complete excision with wide margins is offered as long as functional and/or cosmetic results are acceptable; however, for some anatomic locations, such as parameningeal sites, chemotherapy and RT are the standard of care rather than surgical resection. When surgical excision is not possible, or when surgery is incomplete, RT is often used for local control. Risk-adapted therapy guidelines assist in treatment decisions for adjuvant RT and adjuvant chemotherapy, including selection of the appropriate chemotherapy regimen.

●Angiosarcoma – Angiosarcomas are aggressive tumors arising in either blood or lymphatic vessels; the scalp and face are the most common sites of origin. (See 'Angiosarcoma' above.)

•Resectable disease – For patients with local and locoregional disease that is resectable, we prefer complete surgical resection with wide margins. (See 'Resectable disease' above.)

For almost all patients who undergo resection, we suggest preoperative or postoperative RT (Grade 2B) due to the propensity for insidious local infiltration. The role of adjuvant or neoadjuvant chemotherapy is unclear, and we do not offer it routinely.

•Locally advanced, unresectable disease – For patients with locally advanced, unresectable tumors, neoadjuvant chemotherapy and/or RT may allow some patients with locally advanced lesions to undergo potentially less mutilating surgery. (See 'Unresectable disease' above.)

●Desmoid tumors and dermatofibrosarcoma protuberans – Desmoid tumors and DFSP are locally aggressive neoplasms with a propensity for local recurrence despite complete resection. (See 'Desmoids and dermatofibrosarcoma protuberans' above.)

•Desmoid tumors – For patients with stable, asymptomatic desmoid tumors, an initial period of close observation is an acceptable strategy. Treatment may be initiated at the onset of symptomatic and/or progressive disease, if there is imminent risk to adjacent structures or if the tumor creates cosmetic concerns. Initial treatment may include surgery or systemic therapy alone.

•For those with resectable desmoid tumors, options for treatment include complete excision when possible, and/or radiation for recurrent, marginally resectable, or unresectable tumors. Cryotherapy is used in some centers as an alternative to surgery for accessible lesions, either as initial or salvage therapy.

•For those with unresectable or recurrent desmoid tumors, options for initial systemic therapy include chemotherapy, hormonal therapy, or targeted agents (eg, sorafenib). (See "Desmoid tumors: Systemic therapy", section on 'Efficacy and toxicity of different treatments'.)

•Dermatofibrosarcoma protuberans – For patients with DFSP of the head and neck, the preferred initial treatment is resection with pathologically negative margins. Although available data are limited, Mohs micrographic surgery may permit greater local control while minimizing the amount of normal tissue that must be sacrificed as compared with wide local excision.

●Other histologies – For other adult-type soft tissue sarcomas that do not fit into any of these categories, treatment principles for these tumors should follow those used for tumors outside of the head and neck region. (See 'Other adult soft tissue sarcomas' above.)

•Extirpative surgery with wide margins is preferred, if feasible.

•We recommend adjuvant RT (either preoperative or postoperative) for all high-grade tumors and any malignant tumor (even low-grade) treated with less than wide margin excisional surgery (Grade 1B).

•The benefit of adjuvant chemotherapy following optimal local therapy remains uncertain and can be a function of chemotherapy sensitivity. We do not routinely pursue this approach for soft tissue sarcomas arising in the head and neck; however, it may be considered for patients with a good performance status who are at high risk of a local recurrence or metastatic disease.

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Steven J Charous, MD, FACS, who contributed to earlier versions of this topic review.