Sinonasal Teratocarcinosarcoma of the Head and Neck: A Report of 10 Patients Treated at a Single Institution and Comparison With Reported Series

Objectives  To present the clinicopathologic features of 10 sinonasal teratocarcinosarcomas managed at a single center. Teratocarcinosarcoma is a rare morphologically heterogeneous and highly malignant neoplasm. Previous reports of these tumors have focused on their differential diagnosis and histogenesis and consisted of individual case reports and consultation based series.

Design  Review of patient medical records and microscopic slides of all tumor tissues. The histopathologic features for each tumor and the demographic, clinical, treatment, and follow-up information were recorded for each patient. Also, a comparison with previously reported series was performed.

Setting  The University of Texas M. D. Anderson Cancer Center.

Patients  Ten men ranging in age from 35 to 69 years (mean age, 53 years) were included in the study. They all experienced a short course of symptoms, with an average duration of 3.5 months, and 9 presented with nasal obstruction and epistaxis. Nine patients were treated with both surgery and irradiation.

Results  Histologically, the tumors showed primitive neuroepithelial elements and various malignant epithelial and mesenchymal components. Six patients had no evidence of disease by the end of follow-up, which ranged from 72 to 372 months. Three patients died of disease, and 1 patient was lost to follow-up.

Conclusion  Sinonasal teratocarcinosarcoma of the head and neck is a histologically and biologically heterogeneous malignant neoplasm that is best managed with surgery and postoperative radiotherapy.

Sinonasal teratocarcinosarcoma is an extremely rare malignant neoplasm of uncertain histogenesis.^1,2 Because of the infrequency and the complex phenotypic composition, these lesions are often misdiagnosed, leading to management difficulties.^3-10 The origin of these tumors remains undetermined, although a stem or pluripotential progenitor cell with multidirectional differentiation is a likely candidate.¹¹ Phenotypically, these tumors are composed of benign neural elements and various malignant epithelial and mesenchymal components.¹² The carcinoma may be either squamous or adenocarcinoma, and the mesenchymal component may manifest spindle, smooth, skeletal muscle, cartilage, and bone features.

Reports of the clinical findings of these tumors differ widely in patient presentations, management techniques, and biological outcomes.^5-14 This wide variation is largely related to the nature of the publications: single case reports and consultative series. Furthermore, the objectives of the vast majority of these studies centered on the pathomorphology, differential diagnosis, and histogenesis, with less emphasis on the clinical behavior and treatment outcome.^15-23 The clinical features and treatment of patients with these tumors, therefore, remained to be addressed.²⁴ In the present study, to our knowledge the largest from a single institution, we present our experience with 10 sinonasal teratocarcinosarcoma cases and a review of the literature.

Ten sinonasal teratocarcinosarcomas were identified through an extensive review of sinonasal tumors at The University of Texas M. D. Anderson Cancer Center, Department of Pathology, between 1965 and 2000. The clinicopathologic, treatment, and follow-up information is summarized in the Table. All 10 patients were men who ranged in age from 35 to 69 years (average age, 53 years). Nine of the 10 presented with nasal obstruction and epistaxis, and 1 with only epistaxis. The course of their symptoms was fairly short, with durations ranging from 1 to 8 months (average duration, 3.5 months). The initial diagnoses of these cases included poorly differentiated malignant neoplasm, poorly differentiated squamous carcinoma, malignant mixed mesodermal tumor, spindle cell squamous carcinoma, teratocarcinosarcoma, and neuroendocrine tumors, among others.

Histologically, all 10 tumors manifested variable phenotypic features representing the main histogenetic components of this entity. All tumors contained malignant neuroepithelial elements and various epithelial and mesenchymal malignant components (Figure). The dominant malignant phenotypes were adenocarcinoma and squamous carcinoma in 8 cases, rhabdomyosarcoma in 6, and tumor contained within chondrosarcoma areas in 2. In all tumors, however, differing components of neuroepithelial, epithelial, and mesenchymal malignant areas were present.

Computed tomography images were reviewed and established that 9 of the tumors were localized to the nasal cavity. The location was left sided in 6 and right sided in 4 of the patients. Five patients had tumor extending into the maxillary sinus; 6 patients had extension into the ethmoid sinus; and 2 had extension into the sphenoid sinus. One patient had a mass located only in the paranasal sinuses with no mass in the nasal cavity.

All patients but 1 underwent surgery as the initial treatment, and this included 4 maxillectomies, 2 sphenoidectomies, 3 ethmoidectomies, and 1 orbital exenteration. Of the 9 patients who underwent postoperative radiotherapy, information on the dose and the rate of radiation administered was available for 7 patients. Five of these were given 60 Gy in 30 fractions; 1 received 54 Gy in 27 fractions; and 1 received 25 Gy in 5 fractions. Radiation therapy was directed to the primary site only, and no patient received elective nodal irradiation. A variety of megavoltage beam types, energies, and techniques were used over the long interval of this review. Only 1 patient was preoperatively treated with chemotherapy and died 1 day postoperatively of myocardial infarction. Eight patients had adequate follow-up, and 1 patient was lost to follow-up. Of the 8 patients with follow-up information, 3 died of locoregional failure at an average of 15 months after treatment, and 5 had no evidence of disease after long follow-up (average follow-up, 200 months).

This study, to our knowledge the largest series performed at a single institution, presents the salient pathologic and clinical characteristics and the treatment outcomes of patients with these rare tumors. All patients were men, with an average age of 53 years. They most frequently presented with a brief history of epistaxis and nasal obstruction. Rare symptoms included eye and/or facial pain, expectoration of tissue, epiphora, headache, vision loss, exophthalmos, and anosmia. One of our patients presented with syndrome of inappropriate antidiuretic hormone secretion and a headache, while another presented with headache, somnolence, and apathy. In previously reported series, most of the patients were also male; only 11% were female with similar symptoms.^2-15 The duration of symptoms in our patients averaged 3.5 months and was comparable to that reported in most of the reported studies.^5-21 The short onset in these cases is most likely due to the rapid growth and the extensive local destruction by this entity compared with other tumors of the sinonasal tract.^3,14,25

Most of the tumors in our series, as in previous reports, showed extension to adjacent structures at the time of presentation, with the nasal cavity and/or the paranasal sinuses being the most frequently affected. In some cases, the site origin could not be determined, most likely owing to the rapid growth and the involvement of adjacent structures. Restricted involvement of the paranasal sinuses was observed in a small number of cases. In decreasing order of frequency, tumors were found in the orbit, skull base, cribriform plate, nasopharynx, and anterior cranial fossa.^16-20

Histopathologically, most of our patients presented with different diagnoses of diverse histogenesis that included different epithelial, germ cell, and mesenchymal malignant neoplasms. This diversity of diagnoses is mainly related to unfamiliarity and the marked phenotypic heterogeneity of these tumors.¹⁰ Accurate diagnosis requires adequate diagnostic specimens and experience with this entity.^{11,12,20,21,25-30} Features that may aid in the recognition of these tumors are the presence of immature neural tissue and fetal epithelial structure admixed with various malignant and mesenchymal elements.^11,12,21-24 Although the histogenesis of these tumors remains a subject of debate, an origin from a primitive neural crest or stem or progenitor cell with multidirectional differentiation is currently favored.^9,11

The management of all of our cases was generally similar: 9 of our patients underwent surgery and postoperative radiotherapy. Of these, 5 survived with no evidence of recurrence; 1 was lost to follow-up; and 3 died of their disease due to locoregional failure. These findings, along with those of previously reported studies, show a recurrence rate of approximately 37% and a mortality rate of 30%.^16,24 In previous series, however, patients who were treated with surgery alone had a high recurrence rate and moderate mortality rate in contrast to those receiving radiation treatment.^16,24 Only 1 of our patients, who received chemotherapy and radiotherapy, developed cervical metastasis and died of disease.

In summary, sinonasal teratocarcinosarcoma is a rare tumor characterized by the presence of benign and malignant epithelial, mesenchymal, and neural components. Owing to its heterogeneous histologic appearance, adequate sampling and recognition of all the components of this type of tumor are needed for its correct diagnosis. Sinonasal teratocarcinosarcoma has been reported to be a highly aggressive tumor. However, the long survival seen in some patients underscores the importance of tumor staging and assessing resectability in patients with sinonasal teratocarcinosarcoma. Surgical removal, as complete as possible, and postoperative adjuvant therapy seem to be the treatments of choice for patients with sinonasal teratocarcinosarcoma. Future individualized therapy may also hold promise.³¹

Correspondence: Adel K. El-Naggar, MD, PhD, Department of Pathology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Unit 085, Houston, TX 77030 (anaggar@mdanderson.org).

Submitted for Publication: June 15, 2007; final revision received September 7, 2007; accepted September 11, 2007.

Author Contributions: Dr El-Naggar had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Smith, Luna, Malpica, Rosenthal, and El-Naggar. Acquisition of data: Smith, Malpica, and Rosenthal. Analysis and interpretation of data: Smith, Hessel, and Rosenthal. Drafting of the manuscript: Smith. Critical revision of the manuscript for important intellectual content: Smith, Hessel, Luna, Malpica, Rosenthal, and El-Naggar. Administrative, technical, and material support: Smith, Rosenthal, and El-Naggar. Study supervision: Hessel, Luna, Malpica, Rosenthal, and El-Naggar.

Financial Disclosure: None reported.

Funding/Support: This work was supported in part by the Kenneth D. Müller Professorship (Dr El-Naggar).