gms | German Medical Science

Sarcomas of the head and neck are rare malignancies constituting about 0.8% of all head and neck tumors. These tumors do not commonly manifest as primary malignancies in the head and neck region, exept in the pediatric population where nearly 35% of all sarcomas affect head and neck sites. The rarity of sarcomas, and the multitude of histologic subtypes, makes definitive diagnosis difficult. Thus, an experienced pathologist is the key to appropriate evaluation and forms the basis for treatment selection and thus prognosis. Additionally, the complexity of head and neck anatomy, especially regarding function and cosmesis, makes optimal treatment difficult to determine in many cases.

Sarcomas can be classified according to various criteria [Ref. 1], [Ref. 2], [Ref. 10], [Ref. 12], [Ref. 13]. In general, these neoplasms are designated by their tissue of origin, histologic grade, and the anatomical subsite of the head and neck region in which they are found. Sarcomas can arise from either bony or soft tissue, depending on the mesenchymal cells from which they derive. Osteosarcoma, malignant fibrous histiocytoma (MFH), rhabdomyosarcoma (RMS), angiosarcoma, synovial sarcoma and Ewing sarcoma are generally considered to be high grade lesions [Ref. 2], [Ref. 7], [Ref. 12]. Dermatofibrosarcoma.protuberans, desmoid tumors, and atypical lipomatous tumors are almost universally low-grade neoplasms [Ref. 13]. Other types of sarcomas, including chondrosarcoma, fibrosarcoma, leiomyosarcoma, liposarcoma, neurogenic sarcoma,and hemangiopericytoma require individualized grading according to pathologic analysis.

Genetic and environmental factors can contribute to the development of sarcomas. Several genetic disorders, often arising from germeline mutations in tumor suppressor genes, are clearly associated with an increased risk of these neoplasms. The Li-Fraumeni syndrome, an autosomal disorder involving a germeline mutation of the p53 tumor suppressor gene leads to an increase in breast cancers, soft tissue sarcomas, central nervous system malignancies, leukemia, and adrenocortical carcinomas [Ref. 14]. Another tumor suppressor gene, Rb 1, is known to cause the hereditary form of retinoblastoma and other types of bony and soft tissue sarcomas [Ref. 3]. Neurofibromatosis type I is associated with elevated rates of childhood RMS, liposarcoma, and fibrosarcoma. Many other genetic disorders, including Gardner syndrome and hereditary hemochromatosis are also liked to sarcomas. In addition to predisposing host factors several environmental conditions have been linked to the development of sarcomas. Head and neck ionizing external beam radiation is believed to contribute to sarcoma risk even though the relative risk of developing a sarcoma after radiation is difficult to determine because of inadequate long term observation of these patients and the relative rarity of these tumors. In an evaluation of patients treated in Taiwan for nasopharyngeal carcinoma using radiotherapy the 15-year cumulative incidence of sarcomas was 2.2% [Ref. 6]. Increased risk has also been reported in people exposed to various radioisotopes [Ref. 8], [Ref. 14] and in electrical workers who work near high electromagnetic fields [Ref. 11]. Certain chemicals, such as phenoxyacetic acid-based herbicides, agent orange, dioxin and inorganic arsenic have been correlated to the formation of soft tissue sarcomas [Ref. 9], [Ref. 14]. Parental drug use, particularly cocaine and marijuana, in the year preceding birth of a child increases the risk of pediatric RMS [Ref. 4]. Despite these known risk factors only a minority of sarcomas can be attributed to a defined genetic disorder or known environmental exposure.

In the following analysis we present the clinical aspects, treatment modalities and outcome of adult head and neck sarcoma patients treated at Munich ENT department between 1988 and 2002. As a consequence we present a multimodal therapeutic plan implemented in EORTC trials and supported by the oncology group of the German head and neck society.

25 adult patients suffering from head and neck sarcomas have been treated between 1988 and 2002. 8 patients (32%) suffered from chondro- and osteosarcomas, 5 (20%) from carcino- and angiosarcomas, and 12 (48%) from myo- and fibrosarcomas. Mean age was 49.8 years (18–81) years, 16 patients were male, 9 female. Chondro- and osteosarcomas predominantly occurred in males (87,5%) while angio- and carcinosarcomas was more frequently found in females (60%).

Myo- and fibrosarcomas were predominatly diagnosed in the oral cavity (8/12) while the remaining were distributed throughout the head and neck area (nose, larynx, oropharynx, and hypopharynx). Chondro- and osteosarcomas were located in the scull base (6/8) and larynx (2/8). Angio- and carcinosarcomas were distributed throughout all sites of the head and neck area without any predisposition.

20/25 (80%) of the patients presented with a painless mass usually found under intact mucosa. Other symptoms were severe weight loss (5/25, 20%) and pain (4/25, 16%). Site specific symptoms, like hoarseness, dyspnea, or nasal bleeding subsequently became evident, but were present at first presentation in only 3/25 (12%) of the patients. The time interval of symptoms was rather short. 21/25 patients (84%) had a history of symptoms of less than 2 month. None of the symptoms could be attributed to a certain histological subtype.

In contrast, tumor extension was T3/T4 in 17/25 (68%) of the patients and T1/T2 in 8/25 (32%) cases. Lymph node involvement (6/12) and distant metastases (2/12) were only found in myo- and fibrosarcomas but not in chondro and osteosarcomas or angio- and carcinosarcomas.

Patients suffering from low grade sarcomas were predominantly treated surgically (8/25). High grade sarcomas were predominantly resected and subsequently treated with external beam radiation (12/25). Chemoradiotherapy was supplied in 3/25 patients while 2/25 patients received palliative treatment.

During a mean follow-up of 42.3 month a tumor recurrence was diagnosed in 13 (52%) of the patients. Recurrences were extremely common in patients suffering from sarcomas at anatomical regions were free margins were difficult to achieve (scull base region, pterygopalatine fossa).

While soft tissue sarcomas predominantly were diagnosed in the oral cavity and nose, chondro- and osteosarcomas were usually found at the scull base and larynx. Symptoms are unspecific and most patients have a very short history of symptoms. A painless mass, commonly found in these patients, may guide the clinician to think of a sarcoma [Ref. 10]. Lymph node metastases rarely occur while distant metastases are not uncommon, particularly in high grade sarcomas, thus diagnostic evaluation particularly for lung metastases should be implemented into high grade sarcoma staging. Up to now, surgery generally has been recommended as the primary method of treatment for achieving local control, except in those high-grade tumors arising in sites not amenable to resection [Ref. 2], [Ref. 10], [Ref. 12], [Ref. 13]. Adjuvant radiotherapy is generally recommended for high-grade sarcomas, large tumors and close or positive surgical margins [Ref. 1], [Ref. 5], [Ref. 10].

In the presented analysis the recurrence rate was 52% in the follow-up period of 42.3 month using this therapeutic regime. This is in line with the literature reporting a 3–5 year survival rate of adult head and neck sarcomas of 35–72%. The 5 year survival after surgical resection with positive margins varies between 0% and 32% [Ref. 2], [Ref. 10], [Ref. 12], [Ref. 13].

We now present a therapeutic concept implementing neoadjuvant chemotherapy (adriamycin / ifosfamid) to determine responsiveness to chemotherapy which can help the clinician select patients who may benefit from systemic postoperative therapy (see Figure 1 [Fig. 1]). All adult patients suffering from high grade soft tissue sarcomas are included in the study. Patients suffering from low grade sarcomas who are not amenable to surgical resection due to EORTC criteria are also included. EORTC criteria demand 1 cm free tissue around the tumor to state free margins. As this is difficult to achieve at many anatomical sites in the head and neck region these patients may also be included into the multimodal treatment. All responders will undergo surgery. As previous studies using the protocol could show no differences in recurrence free survival between patients resected with free margins (R0) and minimal residual disease (R1 resection) in the chemotherapy responders less aggressive resection in the patients is recommended (Figure 1 [Fig. 1]). Subsequent radiotherapy is performed followed by a second chemotherapy treatment. As this therapeutic regime has been performed in sarcoma patients of other anatomical sites in the EORTC trial 62961/ESHO-RHT 95 [Ref. 5] we expect a 5 year recurrence free survival of about 60%. We expect to see about 8–12% of early progressions during the initial chemotherapy treatment. In these patients immediate radical surgical treatment should be performed followed by adjuvant radiotherapy.

The study is implemented into the above mentioned EORTC trial and supported by the oncology group of the German head and neck society (http://www.hno-onkologie.de). It is an interdisciplinary study between the departments of medical oncology, ENT, neurosurgery and maxillofacial surgery at Munich university. We invite all colleagues to transfer adult soft tissue sarcoma patients to our department for whole treatment or just for therapeutic planning and enrolment into the study. Please contact C. Matthias, M.D. or U. Herréus, M.D. for ENT patients (089-7095-0), R. Goldbrunner, M.D. (089-7095-0) for neurosurgical patients and G. Mast, M.D. (089-5160-0) for maxillofacial patients. Up to now, even large cancer centres are faced with only few soft tissue head and neck sarcoma patients. Using the presently established treatment (sugery and adjuvant radiotherapy) survival is poor. Therefore, we see the necessity to evaluate multimodal therapeutic procedures like the proposed in clinical trials.