Eur Arch Otorhinolaryngol DOI 10.1007/s00405-013-2807-3
REVIEW ARTICLE
Chondrosarcomas of the head and neck Andre´s Coca-Pelaz • Juan P. Rodrigo • Asterios Triantafyllou • Jennifer L. Hunt • Juan C. Ferna´ndez-Miranda • Primozˇ Strojan • Remco de Bree • Alessandra Rinaldo Robert P. Takes • Alfio Ferlito
•
Received: 8 September 2013 / Accepted: 30 October 2013 Ó Springer-Verlag Berlin Heidelberg 2013
Abstract Chondrosarcoma represents approximately 11 % of all primary malignant bone tumors. It is the second most common sarcoma arising in bone after osteosarcoma. Chondrosarcomas of the head and neck are rare and may involve the sinonasal tract, jaws, larynx or skull base. Depending on the anatomical location, the tumor can produce a variety of symptoms. Computed tomography and magnetic resonance imaging are the preferred imaging modalities. The histology of conventional chondrosarcoma is relatively straightforward; major challenges are the distinction between grade I chondrosarcomas and chondromas, and the differential diagnosis with chondroblastic osteosarcoma and chondroid chordoma. Surgery alone or followed by adjuvant radiotherapy is the treatment of choice. Radiotherapy alone has also been reported to be
This paper was written by members and invitees of the International Head and Neck Scientific Group (www.IHNSG.com).
effective and can be considered if mutilating radical surgery is the only curative alternative. The 5-year survival for chondrosarcoma reaches 80 %; distant metastases and/or local recurrences significantly worsen prognosis. The present review aims to summarize the current state of information about the biology, diagnosis and management of these rare tumors. Keywords Chondrosarcoma Cartilaginous tumor Head and neck Prognosis Therapy
Introduction Chondrosarcoma is a malignant cartilaginous tumor that most commonly occurs in the pelvis, extremities and ribs. This tumor accounts for 11 % of all primary malignant bone tumors. It is the second most common primary bone
A. Coca-Pelaz J. P. Rodrigo Department of Otolaryngology, Hospital Universitario Central de Asturias, Oviedo, Spain
P. Strojan Department of Radiation Oncology, Institute of Oncology, Ljubljana, Slovenia
J. P. Rodrigo Instituto Universitario de Oncologı´a del Principado de Asturias, Oviedo, Spain
R. de Bree Department of Otolaryngology-Head and Neck Surgery, VU University Medical Center, Amsterdam, The Netherlands
A. Triantafyllou Oral Pathology, School of Dentistry, University of Liverpool, Liverpool, UK
A. Rinaldo A. Ferlito (&) ENT Clinic, University of Udine, Piazzale S. Maria della Misericordia, 33100 Udine, Italy e-mail: [email protected]
J. L. Hunt Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA J. C. Ferna´ndez-Miranda Department of Neurosurgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
R. P. Takes Department of Otolaryngology-Head and Neck Surgery, Radboud University Medical Center, Nijmegen, The Netherlands
123
Eur Arch Otorhinolaryngol
neoplasm. 1–12 % of all cases of chondrosarcoma occur in head and neck region [1]. This malignancy represents approximately 0.1 % of all head and neck neoplasms [2]. According to the definition endorsed by the World Health Organization (WHO), head and neck chondrosarcoma (HNCS) is a malignant tumor characterized by the formation of cartilage, but not of bone, by tumor cells [3]. Since the tumor is rare and relatively understudied, the present review aims to summarize the literature and increase awareness of the biology and management of HNCS.
Finally, it is known that chondrosarcomas can develop in non-hereditary skeletal disorders characterized by multiple enchondromas (Ollier disease and Maffucci syndrome), and these conditions are associated with IDH1 and IDH2 mutations [6, 7]. Because of this association, it has been suggested that chondrosarcoma arises from solitary enchondromas. The major issue in proving this theory has been the difficulty in histologically distinguishing between chondroma and grade I chondrosarcoma (see below). Other syndromes and disorders in which chondrosarcoma may arise, including Paget’s disease, are reviewed by Helliwell [8].
Histogenesis The histogenesis of chondrosarcoma is controversial. Suggested theories are summarized in Table 1 and are critically examined below. One theory of origin argues that remnants of cartilage from failures of the ossification of chondrocranium may persist at the skull base (for example, at the temporooccipital junction, middle cranial fossa, sphenoethmoid complex, anterior cranial fossa, and clivus), and give rise to chondrosarcomas [4]. Histologically, it is well known that islands of hyaline cartilage are often present in the area of the nasopalatine duct in adults, and these may account for chondrosarcomas in anterior maxilla. It is, however, difficult to envisage the origin of mandibular chondrosarcomas from remnants of Meckel’s cartilage, an embryonic structure that does not persist after birth. Laryngeal chondrosarcomas usually arise in the cricoid and thyroid cartilages, but are very rare in epiglottis. This distribution corresponds with a second theory endorsing the development of chondrosarcoma from ossified cartilage. On the other hand, the significant under-representation of chondrosarcomas in the mandibular condyle, a site where calcified cartilage is common in adults, argues against this being the only mechanism for development [5]. Another widely propagated theory is that mesenchymal pluripotential cells undergo malignant transformation and differentiate towards a chondrocytic phenotype [4]. This notion is used to ascribe the origin of periosteal chondrosarcoma (see below) to periosteum [3]. Despite the popularity of this theory, there is a paucity of good ‘‘markers’’ to establish the existence and confident morphological recognition of such cells.
Histopathology, immunophenotype and differential diagnosis Table 2 summarizes the histopathological classification of malignant chondrogenic tumors of bone endorsed by the WHO [3]. Processing multiple blocks of representative tissue, including margins in case of resection specimens, and obtaining high-quality routine histological sections stained with hematoxylin and eosin are critical for the interpretation of HNCS. In addition, correlation with clinical and radiological findings is critical in assessing these tumors. The classical appearance of high-grade conventional central chondrosarcoma is relatively straightforward. In a typical case, confluent and cellular nodules of ‘‘malignant cartilage’’ permeate trabecular bone and obliterate marrow. The nodules consist of atypical pleomorphic and mitotically active chondrocytes (chondroblasts) set in typical hematoxyphilic ‘‘cartilaginous’’ matrix, surrounded by layers of spindled cells. The atypical chondrocytes may contain one, two or multiple nuclei and are variably sized. The degrees of cellularity, atypia, mitotic activity and decrease of matrix are used to distinguish between grade II and III tumors, although it should be recognized that this may manifest as a continuum, rather than distinct grade II and III tumors. Formation of metaplastic bone on the cartilaginous nodules can be seen. Distinction between metaplastic bone and definitive malignant osteoid, which is Table 2 Classification of locally aggressive and malignant chondrogenic tumors of bone Conventional central chondrosarcoma (Grade I, II, III) Primary (arising the novo)
Table 1 Histogenesis of chondrosarcoma
Secondary (arising in pre-existing enchondroma)
Cartilage remnants
Periosteal chondrosarcoma
Ossified cartilage
Dedifferentiated chondrosarcoma
Pluripotential mesenchymal/stem cells
Mesenchymal chondrosarcoma Clear cell chondrosarcoma
Precursor syndromes and disorders
123
Eur Arch Otorhinolaryngol
surrounded by and/or contains cuboidal or spindled atypical cells, is a key feature in differentiating chondrosarcoma from chondroblastic osteosarcoma. Major and important challenges in the diagnosis of HNCS are the recognition of the so-called atypical (grade I) tumors that are only locally invasive, and distinction of HNCS and enchondroma. It has been established that many previously reported chondromas in head and neck would now be interpreted as low-grade chondrosarcomas. In fact, these grade I lesions have emerged as the most common subtype of central chondrosarcoma [3]. The criteria for the distinction have been reported [3, 8] and include assessment of nuclear size and hyperchromasia, cellularity and mitoses. Importantly, the number of nuclei and clustering of cells are not considered reliable. While the criteria seem straightforward (for example, nuclei in chondromas are small in relation to the size of the chondrocytes; mitoses are absent from grade I chondrosarcomas), the application of these criteria in clinical practice has proved to be challenging [8]. Nuances in interpretation and experience appear to be of significance and probably account for the reported high interobserver variation regarding the histological grading of HNCS [9]. Despite these challenges, grading should be attempted as it is an important prognosticator [10, 11]. There are a number of histological subtypes of chondrosarcoma, including periosteal, mesenchymal, and clear cell chondrosarcoma, each of which can occur in the head and neck. The rare periosteal chondrosarcoma is a grade I or II tumor, ‘‘stuck’’ on the surface of bone. These tumors are reputedly arising from periosteum and invade adjacent soft tissues, underlying bone cortex and, exceedingly rarely, the marrow [3]. However, the centre of the growth is always extraosseous. Invasion of the soft tissues and cortex together with a large size help in distinguishing periosteal chondrosarcoma from periosteal chondroma [3]. Mesenchymal chondrosarcoma is rather easily recognized for its typical appearance of a ‘‘biphasic’’ tumor, composed of nodules/islands of differentiated cartilage against a background of packed small round cells resembling those seen in Ewing sarcoma and arranged in a characteristic hemangiopericytomatous pattern. The interface between the two components is variously distinct. Immunohistochemistry emphasizes the biphasic appearance with expression of S-100 protein in the islands of cartilage and CD99 being preferentially associated with the round cells [3, 8]. Interestingly, IDH1 and IDH2 mutations are characteristically absent from mesenchymal chondrosarcoma. Sheets of glycogenated, S-100 protein (?) cells with distinct plasmalemma, pale cytoplasm, central small nuclei with little atypia or mitotic activity, limited matrix, and absence of IDH1 and IDH2 mutations characterize the clear cell chondrosarcoma [3].
With the possible exception of the clear cell subtype, immunohistochemistry for S-100 protein seems to be of little value in the histological diagnosis of chondrosarcoma. Differential expression of osteonectin and various matrix metalloproteinases as assessed by immunohistochemistry have been suggested as potential markers for distinguishing chondrosarcoma from chondroblastic osteosarcoma and benign chondrogenic tumors, respectively [8]. Attention has been recently drawn to the immunohistochemical assessment of isocitrate dehydrogenase encoded by a mutant IDH1 gene [3]. Results are of academic merit and in situ hybridization could be the way forward. Specialized antibodies and techniques may not be, however, available to all laboratories and high-quality routine histology, as noted above, currently remains the gold standard in the pathological assessment of HNCS. It has been suggested that more than 13 % of recurrent HNCS show a higher grade of malignancy when they recur [12]. This raises the interesting possibility of progression in conventional chondrosarcoma and could be of significance in the pathogenesis of dedifferentiated subtype. Dedifferentiated chondrosarcoma is characterized by nodules of low-grade conventional chondrosarcoma, which are sharply demarcated from areas of a high-grade sarcoma usually showing spindled, pleomorphic or osteosarcomatous phenotypes [3]. As both low- and high-grade components share IDH1 and other mutations, they probably have a common origin [3]. This contrasts with the absence of IDH1 and IDH2 mutations from mesenchymal chondrosarcoma (see above). Problems in the differential diagnosis have already been discussed. It is noted that distinction between chondrosarcoma and chondroblastic osteosarcoma is of particular significance in jaws because of differences in prognosis and biological behavior of the two tumors therein [5, 8]. With regard to the skull base, distinguishing chondrosarcoma from chondroid chordoma, especially on small biopsies, is another traditional diagnostic challenge. Radiographic similarities between the two tumors increase the difficulties, but immunohistochemistry has made useful contributions. Standard selective ‘‘markers’’ for chordoma include cytokeratins and epithelial membrane antigen [13]; the nuclear immunolocalization of brachyury, a transcription factor encoded by the T gene and influencing notochordal differentiation, is particularly helpful and highly specific [14]. Podoplanin seems to be selectively expressed in chondrosarcoma [15].
Symptomatology and presentation HNCS are locally aggressive growths that rarely metastasize. These tumors usually cause symptoms by
123
Eur Arch Otorhinolaryngol
compression or invasion of important structures within the skull, such as the carotid artery or cranial nerves [16]. Nodal and distant metastases are rarely observed in HNCS. When distant metastases develop, they are most likely to first occur in the lungs [2, 17]. Chondrosarcomas of the skull base can produce diplopia, proptosis, facial pain, headache, cranial nerve deficits (most commonly VI nerve palsy), visual loss and otalgia [4, 7]. HNCS located in the sinonasal tract can cause nasal obstruction, epistaxis, mass effect and pain [18]. In the larynx, the most common initial symptom is dysphonia; when the subglottic area is affected, the main complaint is dyspnea [19–21]. Tumors involving the hyoid bone are unusual [22]. Swelling may be the presenting symptom for the very rare examples of extraskeletal HNCS, such as those occurring at the base of tongue [23]. When the tumor affects pediatric patients, the most frequent sites are the sinonasal tract, mandible and neck, where they produce a mass effect [24].
Diagnosis The clinical appearances of HNCS are usually nonspecific. The principal diagnostic imaging modalities are computed tomography (CT) and magnetic resonance imaging (MRI). CT is a good test to detect the characteristic stippled to coarse calcifications in the tumor. HNCS will appear as expansion of affected cartilage with low attenuation on CT images (Fig. 1). MRI is optimal for delineating the soft tissue involvement, and because of high water content in the matrix, these tumors show very high signal intensity on T2-weighted images (Fig. 2) [25]. Positron emission tomography (PET) scanning with 18-fluorodeoxyglucose (FDG) is unreliable in distinguishing benign from Fig. 1 CT scans of chondrosarcoma located in the larynx (a) and left petrous apex (b)
123
malignant chondrogenic lesions, identifying metastatic disease or distinguishing recurrent tumor from postoperative changes, due to low metabolic activity in low-grade tumors. It can be, however, useful in identifying high-grade HNCS that shows increased standardized uptake value (SUV) due to higher glucose metabolism [26]. Definite diagnosis can be established by incisional biopsy and histopathological examination (see above). Fine needle aspiration (FNA) biopsy is a safe and cost-effective procedure if the lesion is accessible; if used in conjunction with radiographic and clinical findings, a high diagnostic accuracy may be achieved [27]. For staging purposes, the staging system endorsed by the American Joint Committee on Cancer (AJCC) can be used [28].
Treatment Surgical resection is standard for initial therapy of HNCS. The type of surgery depends on histologic grade, tumor extension and location [2, 19, 29]. The key point for local control is to achieve adequate surgical margins [2]. As the skull base is a particularly complex location and primary HNCS is an infiltrative lesion, complete surgical resection will often be difficult to achieve therein. The intricate relationship among these lesions, cranial nerves and the internal carotid artery (ICA) possesses additional difficulties and increases the possibility of potentially severe and disabling complications, such as lower cranial nerve palsies and ICA injury. Balloon test occlusion of the ICA is performed in cases of vascular encasement, and intraoperative cranial nerve monitoring is recommended [30]. In cases where tumor-free margins are impossible to
Eur Arch Otorhinolaryngol Fig. 2 T1-weighted (a) and T2weighted (b) MRI images of a skull-base (left petrous apex) chondrosarcoma
Fig. 3 Preoperative (a, c) and postoperative (b, d) MRI and CT scans. Endoscopic endonasal surgery for subtotal resection of complex chondrosarcoma in a 27-yearold male with severe brainstem compression that resolved after surgery
123
Eur Arch Otorhinolaryngol Fig. 4 Preoperative (a, c) and postoperative (b, d) MRI scans. Endoscopic endonasal surgery for total resection of a petroclival chondrosarcoma in a 47-year-old female with preoperative abducens nerve palsy that resolved after surgery
obtain, surgery aims at decompressing neural or vascular structures and effecting maximal debulking [31] followed by adjuvant radiotherapy or close observation [32]. Multiple cranial base approaches have been used to access skull-base chondrosarcomas, but the recent introduction of endonasal endoscopic surgery (EES) has provided an additional option that is ideal for many cases (Figs. 3, 4). EES uses a ventral and extradural route into the skull base that facilitates direct access to the petroclival region and foramen lacerum by exposing the paraclival and lacerum segments of the ICA [33, 34]. In fact, the ICA is frequently displaced antero-laterally by the tumor, which increases the working corridor into the lesion. Similarly, cranial nerves are usually displaced laterally at the periphery of the tumor,
123
making the medial to lateral working corridor provided by the endonasal route ideal to deal with these tumors [35]. Endonasal surgical access to the jugular foramen, where some of these tumors may extend, is achieved by manipulation and/or transection of the Eustachian tube [36]. Progressive experience with EES has reduced cerebrospinal fluid leak rates to levels comparable to open skull-base approaches, but the complexity of skull-base chondrosarcomas mandates significant surgical experience with EES before attempting resection [37]. When tumors extend beyond the limits of EES, traditional open approaches are best suited. These include subfrontal, transbasal and orbitozygomatic approaches for tumors extending laterally to the optic nerves; transpetrosal approaches for tumors
Eur Arch Otorhinolaryngol
invading the jugular foramen and petrous bone; retrosigmoid and far lateral approaches for tumors extending postero-laterally along the posterior fossa; and transoral or transcervical approaches for tumors extending below the axis (C2). In the larynx, a conservative surgical approach (open or endoscopic) is often chosen in case of low-grade chondrosarcoma, with the objective of organ preservation. Two types of open conservational approaches are possible: the thyrotomy (laryngofissure) approach and the external approach. The objective in both approaches is to maintain a functional larynx, which requires the preservation of the cricoarytenoid joint, posterior cricothyroid muscle and recurrent laryngeal nerve. The external approach carries a higher risk of injuring these structures. Tiwari et al. [38] reported a series of five patients with low-grade chondrosarcoma of the cricoid, which had been initially treated by thyrotomy and were followed for a period of 5–18 years. Three of the patients were further treated by thyrotomy for recurrence and only one patient eventually underwent total laryngectomy; none died from the disease. Piazza et al. [39] recently reported their retrospective series of 16 low (n = 11) and intermediate (n = 5) grade laryngeal chondrosarcomas treated by endoscopic (n = 4) and open (n = 12) conservative (organ preservation) surgery, i.e. open partial laryngectomy and cricotracheal resection and anastomoses. One patient underwent total laryngectomy 11 years after conservative surgery for recurrent symptomatic disease. Two patients died of unrelated causes. At last follow-up, seven patients were alive with asymptomatic stable disease and seven patients were alive without any evidence of persistent disease. The authors reported that all patients regained regular oral feeding and voice ranging from normal to moderate dysphonic after conservative surgery [39]. In high-grade chondrosarcomas, the surgical option is total laryngectomy. Given the low incidence of lymph node metastasis, (elective) neck dissection is not necessary [20, 40]. Tracheal chondrosarcomas can be managed with resection and end-to-end anastomosis [41]. Several reconstructions after partial laryngectomy for chondrosarcoma have been described: local flaps, autogenic rib implants and tracheal autotransplantation. Briefly, the two-stage procedure is as follows: During the first operation, extended hemilaryngectomy is performed, and a radial forearm flap is transferred to the neck, the fascial paddle being wrapped around the upper segment of cervical trachea and the skin paddle temporarily closing the surgical defect. Definitive reconstruction is undertaken after 2–3 months and consists of removal of the skin paddle and transplantation of a patch of re-vascularized cervical trachea to reconstruct the laryngeal defect. Delaere et al. [42] reported promising results in seven patients with chondrosarcoma of the cricoid cartilage with this technique.
In case of an asymptomatic low-grade lesion in a surgically difficult to access location, the optimal management is controversial. A conservative wait-and-see policy implementing CT scanning at regular time intervals can be considered, with surgery performed when the lesion grows and produces symptoms [7]. There are various views regarding the radiosensitivity of HNCS [43]. As this is a slowly growing tumor with a low fraction of dividing cells, it is considered as ‘‘relatively’’ radioresistant. It is generally accepted that the role of radiotherapy is for adjuvant treatment in cases of highly probable, residual disease after surgery, and for palliation in patients with unresectable lesions or unsuitable for major surgery [32, 44–46]. In low-grade chondrosarcomas with negative surgical margins, adjuvant radiotherapy is not indicated. In contrast, it is recommended in cases of highgrade chondrosarcoma due to the more aggressive behavior [47]. Prognosis is also improved in patients receiving adjuvant radiotherapy for histopathologically involved margins [32, 47, 48]. There are only case reports suggesting that radiotherapy alone can be successful, particularly in patients with laryngeal chondrosarcoma for whom total laryngectomy was the only surgical alternative [49, 50]. With the emergence of new types of radiotherapy such as intensity-modulated radiotherapy (IMRT), proton beam radiation or stereotactic fractionated radiotherapy, higher doses of radiation can be delivered and result in improved control rates for these tumors. Implementation of these new procedures in head and neck is of importance given the close proximity of vital structures [4, 51]. So far there is no convincing evidence that a particular procedure is clearly superior [32]. In skull-base chondrosarcomas, chargedparticle radiotherapy, specifically proton beam therapy, has gained favor over other radiotherapy modalities because of improved physical dose characteristics resulting in superior conformality and lower dose to adjacent structures. In series reporting the results of proton beam adjuvant therapy, substantially higher median irradiation doses were administered when compared to photon therapy, which ranged from 60 to 79 cobalt gray equivalent (CGE) [52]. In addition to proton beams, carbon-ion particle therapy has been successfully used for the treatment of skull-base chondrosarcomas. Carbon ions, having comparable physical characteristics to proton beams, also result in dosedistribution advantages in comparison with conventional photons and electrons. As high linear energy transfer (LET) beams, carbon ions also have a higher biological effectiveness than either protons or photons. In a series of 54 patients with skull-base chondrosarcomas treated with carbon ions, a tumor control rate of 89 % and an overall survival of 98 % at 5 years were reported [53]. The benefit of chemotherapy is negligible. Low-grade HNCSs seem to be chemoresistant, which possibly reflects
123
Eur Arch Otorhinolaryngol
their slow rate of growth with small fraction of proliferating cells, variable matrix and poor vascularization. Chemotherapy can be, however, used in high-grade chondrosarcomas, clinically aggressive tumors with rapid local recurrence and cases with a high probability of metastasis [54].
Prognosis Similar to other tumors, complete resection of HNCS significantly affects prognosis. Local recurrence is the main cause of death. Other factors influencing prognosis are stage at diagnosis, histopathological grade of the lesion (poor prognosis for high-grade tumors) and location. Particular histological subtypes, e.g. mesenchymal (see above), are more aggressive and show a poor prognosis [1, 47, 55]. In general, lymph node metastases are unusual (5 %) and distant metastases occur only in 7–18 %. However, high-grade chondrosarcomas may present with distant metastases in up to 71 % of cases [1, 54, 56]. Survival rates for HNCS range between 44 and 88 % [2, 19, 56–61]. Long-term follow-up is recommended because the tumors can give rise to local recurrence or even metastases many years after initial diagnosis.
Conclusion HNCS is a rare tumor––hence, it is difficult to establish an optimal treatment protocol. Surgery followed by adjuvant radiotherapy in cases with an increased risk of local recurrence is the treatment of choice. Conservative types of surgery should be considered for preservation of organs and function, depending on the site and grade of the tumor. Survival is generally good, but varying figures have been reported due to occurrence of aggressive histological types. Given the low incidence of HNCS and the complexity of the head and neck region, management should be ideally centralized in specialized centers with dedicated multidisciplinary teams.
References 1. Koch BB, Karnell LH, Hoffman HT et al (2000) National cancer database report on chondrosarcoma of the head and neck. Head Neck 22:408–425 2. Lee SY, Lim YC, Song MH et al (2005) Chondrosarcoma of the head and neck. Yonsei Med J 46:228–232 3. Fletcher CDM, Bridge JA, Hogendoorn PCW et al (2013) WHO classification of tumors of soft tissue and bone. IARC, Lyon 4. Neff B, Sataloff RT, Storey L et al (2002) Chondrosarcoma of the skull base. Laryngoscope 112:134–139
123
5. Sciubba JJ, Fantasia JE, Kahn LB (2001) Tumors and cysts of the jaws. Atlas of tumor pathology, fascicle 29, 3rd series. Armed Forces Institute of Pathology, Washington DC 6. Rosenberg A, Nielsen P, Keel SB et al (1999) Chondrosarcomas of the base of skull. Am J Surg Pathol 23:1370–1378 7. Lustig LR, Sciubba J, Holliday MJ (2007) Chondrosarcomas of the skull base and temporal bone. J Laryngol Otol 121:725–735 8. Helliwell TR (1999) Central cartilaginous neoplasms of bone. In: Helliwell TR (ed) Pathology of bone and joint neoplasms. Major problems in pathology, vol 37. Saunders, Philadelphia, pp 193–214 9. Eefting D, Schrage YM, Geirnaerdt MJ et al (2009) Assessment of interobserver variability and histologic parameters to improve reliability in classification and grading of central cartilaginous tumors. Am J Surg Pathol 33:50–57 10. Evans HL, Ayala AG, Romsdahl MM (1977) Prognostic factors in chondrosarcoma of bone: a clinicopathologic analysis with emphasis on histologic grading. Cancer 40:818–831 11. Giuffrida AY, Burgueno JE, Koniaris LG et al (2009) Chondrosarcoma in the United States (1973 to 2003): an analysis of 2890 cases from the SEER database. J Bone Joint Surg Am 91:1063–1072 12. Grimer RJ, Gosheger G, Taminiau A et al (2007) Dedifferentiated chondrosarcoma: prognostic factors and outcome from a European group. Eur J Cancer 43:2060–2065 13. Mitchell A, Scheithauer BW, Unni KK et al (1993) Chordoma and chondroid neoplasms of the spheno-occiput. An immunohistochemical study of 41 cases with prognostic and nosologic implications. Cancer 72:2943–2949 14. Vujovic S, Henderson S, Presneau N et al (2006) Brachyury, a crucial regulator of notochordal development, is a novel biomarker for chordomas. J Pathol 209:157–165 15. Huse JT, Pasha TL, Zhang PJ (2007) D2-40 functions as an effective chondroid marker distinguishing true chondroid tumors from chordoma. Acta Neuropathol 113:87–94 16. Weber A, Brown E, Hug E et al (1995) Cartilaginous tumors and chordomas of the cranial base. Otolaryngol Clin North Am 28:453–471 17. Hong P, Taylor MS, Trites JR et al (2009) Chondrosarcoma of the head and neck: report of 11 cases and literature review. J Otolaryngol Head Neck Surg 38:279–285 18. Knott PD, Gannon FH, Thompson LD (2003) Mesenchymal chondrosarcoma of the sinonasal tract: a clinicopathological study of 13 cases with a review of the literature. Laryngoscope 113:783–790 19. Obeso S, Llorente JL, Dı´az-Molina JP et al (2010) Surgical treatment of head and neck chondrosarcomas. Acta Otorrinolaryngol Esp 61:262–271 20. Buda I, Hod R, Feinmesser R et al (2012) Chondrosarcoma of the larynx. Isr Med Assoc J 14:681–684 21. Rinaldo A, Howard DJ, Ferlito A (2000) Laryngeal chondrosarcoma: a 24-year experience at the Royal National Throat, Nose and Ear Hospital. Acta Otolaryngol 120:680–688 22. Zhang I, Zaorsky N, Abraham J et al (2013) Chondrosarcoma of the hyoid bone: case report and a review of current management options. Head Neck. doi:10.1002/hed.23373 23. Al-Rawi M, Harper T, Bafakih F (2013) Chondrosarcoma of the tongue: a case report and a review of the literature. Laryngoscope 123:418–421 24. Gadwal SR, Fanburg-Smith JC, Gannon FH et al (2000) Primary chondrosarcoma of the head and neck in pediatric patients: a clinicopathologic study of 14 cases with a review of the literature. Cancer 88:2181–2188 25. Murphey MD, Walker EA, Wilson AJ et al (2003) From the archives of the AFIP: imaging of primary chondrosarcoma: radiologic-pathologic correlation. Radiographics 23:1245–1278
Eur Arch Otorhinolaryngol 26. Lee FY, Yu J, Chang SS et al (2004) Diagnostic value and limitations of fluorine-18 fluorodeoxyglucose positron emission tomography for cartilaginous tumors of bone. J Bone Joint Surg Am 86-A:2677–2685 27. Trembath DG, Dash R, Major NM et al (2003) Cytopathology of mesenchymal chondrosarcomas: a report and comparison of four patients. Cancer 99:211–216 28. Edge SB, Byrd DR, Compton CC et al (2010) American Joint Committee on Cancer Staging Manual, 7th edn. Springer, New York, p 281 29. Prado FO, Nishimoto IN, Perez DE et al (2009) Head and neck chondrosarcoma: analysis of 16 cases. Br J Oral Maxillofac Surg 47:555–557 30. Gardner P, Tormenti M, Pant H et al (2013) Carotid artery injury during endoscopic endonasal skull base surgery: incidence and outcomes. Neurosurgery [Epub ahead of print] 31. Wanebo JE, Bristol RE, Porter RR et al (2006) Management of cranial base chondrosarcomas. Neurosurgery 58:249–255 32. Bloch O, Parsa AT (2013) Skull base chondrosarcoma: evidencebased treatment paradigms. Neurosurg Clin North Am 24:89–96 33. Fernandez-Miranda JC, Gardner PA, Snyderman C et al (2013) Clival chordomas: a pathological, surgical and radiotherapeutic review. Head Neck. doi:10.1002/hed.23415 34. Fernandez-Miranda JC, Morera VA, Snyderman CH et al (2012) Endoscopic endonasal transclival approach to the jugular tubercle. Neurosurgery 71(1 Suppl Operative):146–159 35. Barges-Coll J, Fernandez-Miranda JC, Prevedello DM et al (2010) Avoiding injury to the abducens nerve during expanded endonasal endoscopic surgery: anatomic and clinical case studies. Neurosurgery 67:144–154 36. Morera VA, Fernandez-Miranda JC, Prevedello DM et al (2010) ‘‘Far-medial’’ expanded endonasal approach to the inferior third of the clivus: the transcondylar and transjugular tubercle approaches. Neurosurgery 66(6 Suppl Operative):211–219 37. Koutourousiou M, Gardner PA, Tormenti MJ et al (2012) Endoscopic endonasal approach for resection of skull base chordomas: outcomes and learning curve. Neurosurgery 71:614–625 38. Tiwari R, Mahieu H, Snow G (1999) Long-term results of organ preservation in chondrosarcoma of the cricoid. Eur Arch Otorhinolaryngol 256:271–276 39. Piazza C, Del Bon F, Grazioli P et al (2013) Organ preservation surgery for low- and intermediate-grade laryngeal chondrosarcomas: analysis of 16 cases. Laryngoscope. doi:10.1002/lary.24416 40. Jackson RS, Leon ME, McCaffrey TV (2013) Chondrosarcoma of the subglottic larynx: submucosal microdissection with the operating microscope. Laryngoscope 123:1216–1219 41. Umezu H, Tamura M, Kobayashi S et al (2008) Tracheal chondrosarcoma. Gen Thorac Cardiovasc Surg 56:199–202 42. Delaere PR, Vertriest R, Hermans R (2003) Functional treatment of a large laryngeal chondrosarcoma by tracheal autotransplantation. Ann Otol Rhinol Laryngol 112:678–682
43. Harwood AR, Cummings BJ, Fitzpatrick PJ (1984) Radiotherapy for unusual tumors of the head and neck. J Otolaryngol 13:391–394 44. Harwood AR, Krajbich JI, Fornasier VL (1980) Radiotherapy of chondrosarcoma of bone. Cancer 45:2769–2777 45. McNaney D, Lindberg RD, Ayala AG et al (1982) Fifteen year radiotherapy experience with chondrosarcoma of bone. Int J Radiat Oncol Biol Phys 8:187–190 46. Le A, Ball D, Pitman A et al (2003) Chondrosarcoma of bone complicating Ollier’s disease: report of a favourable response to radiotherapy. Australas Radiol 47:322–324 47. Bloch OG, Jian BJ, Yang I et al (2010) Cranial chondrosarcoma and recurrence: a systematic review. Skull Base 20:149–156 48. Fayda M, Aksu G, Yaman Agaoglu F et al (2009) The role of surgery and radiotherapy in treatment of soft tissue sarcomas of the head and neck region: review of 30 cases. J Craniomaxillofac Surg 37:42–48 49. Gripp S, Pape H, Schmitt G (1998) Chondrosarcoma of the larynx: the role of radiotherapy revisited––a case report and review of the literature. Cancer 82:108–115 50. Dailiana T, Nomikos P, Kapranos N et al (2002) Chondrosarcoma of the larynx: treatment with radiotherapy. Skeletal Radiol 31:547–549 51. Rutz HP, Weber DC, Goitein G et al (2008) Postoperative spotscanning proton radiation therapy for chordoma and chondrosarcoma in children and adolescents: initial experience at Paul Scherrer Institute. Int J Radiat Oncol Biol Phys 71:220–225 52. Fuji H, Nakasu Y, Ishida Y et al (2011) Feasibility of proton beam therapy for chordoma and chondrosarcoma of the skull base. Skull Base 21:201–206 53. Schulz-Ertner D, Nikoghosyan A, Hof H et al (2007) Carbon ion radiotherapy of skull base chondrosarcomas. Int J Radiat Oncol Biol Phys 67:171–177 54. Ruark DS, Schlehaider UK, Shah JP (1992) Chondrosarcomas of the head and neck. World J Surg 16:1010–1016 55. Pellitteri PK, Ferlito A, Fagan JJ et al (2007) Mesenchymal chondrosarcoma of the head and neck. Oral Oncol 43:970–975 56. Finn DG, Goepfert H, Batsakis JG (1984) Chondrosarcoma of the head and neck. Laryngoscope 94:1539–1544 57. Fo¨rander P, Ra¨hn T, Kihlstro¨m L et al (2006) Combination of microsurgery and gamma knife surgery for the treatment of intracranial chondrosarcomas. J Neurosurg 105:18–25 58. Arlen M, Toleefsen HF, Huvos AG et al (1970) Chondrosarcoma of head and neck. Am J Surg 120:456–460 59. Fu YS, Perzin KH (1974) Non-epithelial tumors of the nasal cavity, paranasal sinuses, and nasopharynx: a clinicopathologic study III. Cartilaginous tumors. Cancer 34:453–463 60. Khan MN, Husain Q, Kanumuri VV et al (2013) Management of sinonasal chondrosarcoma: a systematic review of 161 patients. Int Forum Allergy Rhinol 3:670–677 61. Damiani V, Crosetti E, Rizzotto G et al (2013) Well and intermediate differentiated laryngeal chondrosarcoma: toward conservative surgery? Eur Arch Otorhinolaryngol [Epub ahead of print]
123
REVIEW ARTICLE
Chondrosarcomas of the head and neck Andre´s Coca-Pelaz • Juan P. Rodrigo • Asterios Triantafyllou • Jennifer L. Hunt • Juan C. Ferna´ndez-Miranda • Primozˇ Strojan • Remco de Bree • Alessandra Rinaldo Robert P. Takes • Alfio Ferlito
•
Received: 8 September 2013 / Accepted: 30 October 2013 Ó Springer-Verlag Berlin Heidelberg 2013
Abstract Chondrosarcoma represents approximately 11 % of all primary malignant bone tumors. It is the second most common sarcoma arising in bone after osteosarcoma. Chondrosarcomas of the head and neck are rare and may involve the sinonasal tract, jaws, larynx or skull base. Depending on the anatomical location, the tumor can produce a variety of symptoms. Computed tomography and magnetic resonance imaging are the preferred imaging modalities. The histology of conventional chondrosarcoma is relatively straightforward; major challenges are the distinction between grade I chondrosarcomas and chondromas, and the differential diagnosis with chondroblastic osteosarcoma and chondroid chordoma. Surgery alone or followed by adjuvant radiotherapy is the treatment of choice. Radiotherapy alone has also been reported to be
This paper was written by members and invitees of the International Head and Neck Scientific Group (www.IHNSG.com).
effective and can be considered if mutilating radical surgery is the only curative alternative. The 5-year survival for chondrosarcoma reaches 80 %; distant metastases and/or local recurrences significantly worsen prognosis. The present review aims to summarize the current state of information about the biology, diagnosis and management of these rare tumors. Keywords Chondrosarcoma Cartilaginous tumor Head and neck Prognosis Therapy
Introduction Chondrosarcoma is a malignant cartilaginous tumor that most commonly occurs in the pelvis, extremities and ribs. This tumor accounts for 11 % of all primary malignant bone tumors. It is the second most common primary bone
A. Coca-Pelaz J. P. Rodrigo Department of Otolaryngology, Hospital Universitario Central de Asturias, Oviedo, Spain
P. Strojan Department of Radiation Oncology, Institute of Oncology, Ljubljana, Slovenia
J. P. Rodrigo Instituto Universitario de Oncologı´a del Principado de Asturias, Oviedo, Spain
R. de Bree Department of Otolaryngology-Head and Neck Surgery, VU University Medical Center, Amsterdam, The Netherlands
A. Triantafyllou Oral Pathology, School of Dentistry, University of Liverpool, Liverpool, UK
A. Rinaldo A. Ferlito (&) ENT Clinic, University of Udine, Piazzale S. Maria della Misericordia, 33100 Udine, Italy e-mail: [email protected]
J. L. Hunt Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA J. C. Ferna´ndez-Miranda Department of Neurosurgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
R. P. Takes Department of Otolaryngology-Head and Neck Surgery, Radboud University Medical Center, Nijmegen, The Netherlands
123
Eur Arch Otorhinolaryngol
neoplasm. 1–12 % of all cases of chondrosarcoma occur in head and neck region [1]. This malignancy represents approximately 0.1 % of all head and neck neoplasms [2]. According to the definition endorsed by the World Health Organization (WHO), head and neck chondrosarcoma (HNCS) is a malignant tumor characterized by the formation of cartilage, but not of bone, by tumor cells [3]. Since the tumor is rare and relatively understudied, the present review aims to summarize the literature and increase awareness of the biology and management of HNCS.
Finally, it is known that chondrosarcomas can develop in non-hereditary skeletal disorders characterized by multiple enchondromas (Ollier disease and Maffucci syndrome), and these conditions are associated with IDH1 and IDH2 mutations [6, 7]. Because of this association, it has been suggested that chondrosarcoma arises from solitary enchondromas. The major issue in proving this theory has been the difficulty in histologically distinguishing between chondroma and grade I chondrosarcoma (see below). Other syndromes and disorders in which chondrosarcoma may arise, including Paget’s disease, are reviewed by Helliwell [8].
Histogenesis The histogenesis of chondrosarcoma is controversial. Suggested theories are summarized in Table 1 and are critically examined below. One theory of origin argues that remnants of cartilage from failures of the ossification of chondrocranium may persist at the skull base (for example, at the temporooccipital junction, middle cranial fossa, sphenoethmoid complex, anterior cranial fossa, and clivus), and give rise to chondrosarcomas [4]. Histologically, it is well known that islands of hyaline cartilage are often present in the area of the nasopalatine duct in adults, and these may account for chondrosarcomas in anterior maxilla. It is, however, difficult to envisage the origin of mandibular chondrosarcomas from remnants of Meckel’s cartilage, an embryonic structure that does not persist after birth. Laryngeal chondrosarcomas usually arise in the cricoid and thyroid cartilages, but are very rare in epiglottis. This distribution corresponds with a second theory endorsing the development of chondrosarcoma from ossified cartilage. On the other hand, the significant under-representation of chondrosarcomas in the mandibular condyle, a site where calcified cartilage is common in adults, argues against this being the only mechanism for development [5]. Another widely propagated theory is that mesenchymal pluripotential cells undergo malignant transformation and differentiate towards a chondrocytic phenotype [4]. This notion is used to ascribe the origin of periosteal chondrosarcoma (see below) to periosteum [3]. Despite the popularity of this theory, there is a paucity of good ‘‘markers’’ to establish the existence and confident morphological recognition of such cells.
Histopathology, immunophenotype and differential diagnosis Table 2 summarizes the histopathological classification of malignant chondrogenic tumors of bone endorsed by the WHO [3]. Processing multiple blocks of representative tissue, including margins in case of resection specimens, and obtaining high-quality routine histological sections stained with hematoxylin and eosin are critical for the interpretation of HNCS. In addition, correlation with clinical and radiological findings is critical in assessing these tumors. The classical appearance of high-grade conventional central chondrosarcoma is relatively straightforward. In a typical case, confluent and cellular nodules of ‘‘malignant cartilage’’ permeate trabecular bone and obliterate marrow. The nodules consist of atypical pleomorphic and mitotically active chondrocytes (chondroblasts) set in typical hematoxyphilic ‘‘cartilaginous’’ matrix, surrounded by layers of spindled cells. The atypical chondrocytes may contain one, two or multiple nuclei and are variably sized. The degrees of cellularity, atypia, mitotic activity and decrease of matrix are used to distinguish between grade II and III tumors, although it should be recognized that this may manifest as a continuum, rather than distinct grade II and III tumors. Formation of metaplastic bone on the cartilaginous nodules can be seen. Distinction between metaplastic bone and definitive malignant osteoid, which is Table 2 Classification of locally aggressive and malignant chondrogenic tumors of bone Conventional central chondrosarcoma (Grade I, II, III) Primary (arising the novo)
Table 1 Histogenesis of chondrosarcoma
Secondary (arising in pre-existing enchondroma)
Cartilage remnants
Periosteal chondrosarcoma
Ossified cartilage
Dedifferentiated chondrosarcoma
Pluripotential mesenchymal/stem cells
Mesenchymal chondrosarcoma Clear cell chondrosarcoma
Precursor syndromes and disorders
123
Eur Arch Otorhinolaryngol
surrounded by and/or contains cuboidal or spindled atypical cells, is a key feature in differentiating chondrosarcoma from chondroblastic osteosarcoma. Major and important challenges in the diagnosis of HNCS are the recognition of the so-called atypical (grade I) tumors that are only locally invasive, and distinction of HNCS and enchondroma. It has been established that many previously reported chondromas in head and neck would now be interpreted as low-grade chondrosarcomas. In fact, these grade I lesions have emerged as the most common subtype of central chondrosarcoma [3]. The criteria for the distinction have been reported [3, 8] and include assessment of nuclear size and hyperchromasia, cellularity and mitoses. Importantly, the number of nuclei and clustering of cells are not considered reliable. While the criteria seem straightforward (for example, nuclei in chondromas are small in relation to the size of the chondrocytes; mitoses are absent from grade I chondrosarcomas), the application of these criteria in clinical practice has proved to be challenging [8]. Nuances in interpretation and experience appear to be of significance and probably account for the reported high interobserver variation regarding the histological grading of HNCS [9]. Despite these challenges, grading should be attempted as it is an important prognosticator [10, 11]. There are a number of histological subtypes of chondrosarcoma, including periosteal, mesenchymal, and clear cell chondrosarcoma, each of which can occur in the head and neck. The rare periosteal chondrosarcoma is a grade I or II tumor, ‘‘stuck’’ on the surface of bone. These tumors are reputedly arising from periosteum and invade adjacent soft tissues, underlying bone cortex and, exceedingly rarely, the marrow [3]. However, the centre of the growth is always extraosseous. Invasion of the soft tissues and cortex together with a large size help in distinguishing periosteal chondrosarcoma from periosteal chondroma [3]. Mesenchymal chondrosarcoma is rather easily recognized for its typical appearance of a ‘‘biphasic’’ tumor, composed of nodules/islands of differentiated cartilage against a background of packed small round cells resembling those seen in Ewing sarcoma and arranged in a characteristic hemangiopericytomatous pattern. The interface between the two components is variously distinct. Immunohistochemistry emphasizes the biphasic appearance with expression of S-100 protein in the islands of cartilage and CD99 being preferentially associated with the round cells [3, 8]. Interestingly, IDH1 and IDH2 mutations are characteristically absent from mesenchymal chondrosarcoma. Sheets of glycogenated, S-100 protein (?) cells with distinct plasmalemma, pale cytoplasm, central small nuclei with little atypia or mitotic activity, limited matrix, and absence of IDH1 and IDH2 mutations characterize the clear cell chondrosarcoma [3].
With the possible exception of the clear cell subtype, immunohistochemistry for S-100 protein seems to be of little value in the histological diagnosis of chondrosarcoma. Differential expression of osteonectin and various matrix metalloproteinases as assessed by immunohistochemistry have been suggested as potential markers for distinguishing chondrosarcoma from chondroblastic osteosarcoma and benign chondrogenic tumors, respectively [8]. Attention has been recently drawn to the immunohistochemical assessment of isocitrate dehydrogenase encoded by a mutant IDH1 gene [3]. Results are of academic merit and in situ hybridization could be the way forward. Specialized antibodies and techniques may not be, however, available to all laboratories and high-quality routine histology, as noted above, currently remains the gold standard in the pathological assessment of HNCS. It has been suggested that more than 13 % of recurrent HNCS show a higher grade of malignancy when they recur [12]. This raises the interesting possibility of progression in conventional chondrosarcoma and could be of significance in the pathogenesis of dedifferentiated subtype. Dedifferentiated chondrosarcoma is characterized by nodules of low-grade conventional chondrosarcoma, which are sharply demarcated from areas of a high-grade sarcoma usually showing spindled, pleomorphic or osteosarcomatous phenotypes [3]. As both low- and high-grade components share IDH1 and other mutations, they probably have a common origin [3]. This contrasts with the absence of IDH1 and IDH2 mutations from mesenchymal chondrosarcoma (see above). Problems in the differential diagnosis have already been discussed. It is noted that distinction between chondrosarcoma and chondroblastic osteosarcoma is of particular significance in jaws because of differences in prognosis and biological behavior of the two tumors therein [5, 8]. With regard to the skull base, distinguishing chondrosarcoma from chondroid chordoma, especially on small biopsies, is another traditional diagnostic challenge. Radiographic similarities between the two tumors increase the difficulties, but immunohistochemistry has made useful contributions. Standard selective ‘‘markers’’ for chordoma include cytokeratins and epithelial membrane antigen [13]; the nuclear immunolocalization of brachyury, a transcription factor encoded by the T gene and influencing notochordal differentiation, is particularly helpful and highly specific [14]. Podoplanin seems to be selectively expressed in chondrosarcoma [15].
Symptomatology and presentation HNCS are locally aggressive growths that rarely metastasize. These tumors usually cause symptoms by
123
Eur Arch Otorhinolaryngol
compression or invasion of important structures within the skull, such as the carotid artery or cranial nerves [16]. Nodal and distant metastases are rarely observed in HNCS. When distant metastases develop, they are most likely to first occur in the lungs [2, 17]. Chondrosarcomas of the skull base can produce diplopia, proptosis, facial pain, headache, cranial nerve deficits (most commonly VI nerve palsy), visual loss and otalgia [4, 7]. HNCS located in the sinonasal tract can cause nasal obstruction, epistaxis, mass effect and pain [18]. In the larynx, the most common initial symptom is dysphonia; when the subglottic area is affected, the main complaint is dyspnea [19–21]. Tumors involving the hyoid bone are unusual [22]. Swelling may be the presenting symptom for the very rare examples of extraskeletal HNCS, such as those occurring at the base of tongue [23]. When the tumor affects pediatric patients, the most frequent sites are the sinonasal tract, mandible and neck, where they produce a mass effect [24].
Diagnosis The clinical appearances of HNCS are usually nonspecific. The principal diagnostic imaging modalities are computed tomography (CT) and magnetic resonance imaging (MRI). CT is a good test to detect the characteristic stippled to coarse calcifications in the tumor. HNCS will appear as expansion of affected cartilage with low attenuation on CT images (Fig. 1). MRI is optimal for delineating the soft tissue involvement, and because of high water content in the matrix, these tumors show very high signal intensity on T2-weighted images (Fig. 2) [25]. Positron emission tomography (PET) scanning with 18-fluorodeoxyglucose (FDG) is unreliable in distinguishing benign from Fig. 1 CT scans of chondrosarcoma located in the larynx (a) and left petrous apex (b)
123
malignant chondrogenic lesions, identifying metastatic disease or distinguishing recurrent tumor from postoperative changes, due to low metabolic activity in low-grade tumors. It can be, however, useful in identifying high-grade HNCS that shows increased standardized uptake value (SUV) due to higher glucose metabolism [26]. Definite diagnosis can be established by incisional biopsy and histopathological examination (see above). Fine needle aspiration (FNA) biopsy is a safe and cost-effective procedure if the lesion is accessible; if used in conjunction with radiographic and clinical findings, a high diagnostic accuracy may be achieved [27]. For staging purposes, the staging system endorsed by the American Joint Committee on Cancer (AJCC) can be used [28].
Treatment Surgical resection is standard for initial therapy of HNCS. The type of surgery depends on histologic grade, tumor extension and location [2, 19, 29]. The key point for local control is to achieve adequate surgical margins [2]. As the skull base is a particularly complex location and primary HNCS is an infiltrative lesion, complete surgical resection will often be difficult to achieve therein. The intricate relationship among these lesions, cranial nerves and the internal carotid artery (ICA) possesses additional difficulties and increases the possibility of potentially severe and disabling complications, such as lower cranial nerve palsies and ICA injury. Balloon test occlusion of the ICA is performed in cases of vascular encasement, and intraoperative cranial nerve monitoring is recommended [30]. In cases where tumor-free margins are impossible to
Eur Arch Otorhinolaryngol Fig. 2 T1-weighted (a) and T2weighted (b) MRI images of a skull-base (left petrous apex) chondrosarcoma
Fig. 3 Preoperative (a, c) and postoperative (b, d) MRI and CT scans. Endoscopic endonasal surgery for subtotal resection of complex chondrosarcoma in a 27-yearold male with severe brainstem compression that resolved after surgery
123
Eur Arch Otorhinolaryngol Fig. 4 Preoperative (a, c) and postoperative (b, d) MRI scans. Endoscopic endonasal surgery for total resection of a petroclival chondrosarcoma in a 47-year-old female with preoperative abducens nerve palsy that resolved after surgery
obtain, surgery aims at decompressing neural or vascular structures and effecting maximal debulking [31] followed by adjuvant radiotherapy or close observation [32]. Multiple cranial base approaches have been used to access skull-base chondrosarcomas, but the recent introduction of endonasal endoscopic surgery (EES) has provided an additional option that is ideal for many cases (Figs. 3, 4). EES uses a ventral and extradural route into the skull base that facilitates direct access to the petroclival region and foramen lacerum by exposing the paraclival and lacerum segments of the ICA [33, 34]. In fact, the ICA is frequently displaced antero-laterally by the tumor, which increases the working corridor into the lesion. Similarly, cranial nerves are usually displaced laterally at the periphery of the tumor,
123
making the medial to lateral working corridor provided by the endonasal route ideal to deal with these tumors [35]. Endonasal surgical access to the jugular foramen, where some of these tumors may extend, is achieved by manipulation and/or transection of the Eustachian tube [36]. Progressive experience with EES has reduced cerebrospinal fluid leak rates to levels comparable to open skull-base approaches, but the complexity of skull-base chondrosarcomas mandates significant surgical experience with EES before attempting resection [37]. When tumors extend beyond the limits of EES, traditional open approaches are best suited. These include subfrontal, transbasal and orbitozygomatic approaches for tumors extending laterally to the optic nerves; transpetrosal approaches for tumors
Eur Arch Otorhinolaryngol
invading the jugular foramen and petrous bone; retrosigmoid and far lateral approaches for tumors extending postero-laterally along the posterior fossa; and transoral or transcervical approaches for tumors extending below the axis (C2). In the larynx, a conservative surgical approach (open or endoscopic) is often chosen in case of low-grade chondrosarcoma, with the objective of organ preservation. Two types of open conservational approaches are possible: the thyrotomy (laryngofissure) approach and the external approach. The objective in both approaches is to maintain a functional larynx, which requires the preservation of the cricoarytenoid joint, posterior cricothyroid muscle and recurrent laryngeal nerve. The external approach carries a higher risk of injuring these structures. Tiwari et al. [38] reported a series of five patients with low-grade chondrosarcoma of the cricoid, which had been initially treated by thyrotomy and were followed for a period of 5–18 years. Three of the patients were further treated by thyrotomy for recurrence and only one patient eventually underwent total laryngectomy; none died from the disease. Piazza et al. [39] recently reported their retrospective series of 16 low (n = 11) and intermediate (n = 5) grade laryngeal chondrosarcomas treated by endoscopic (n = 4) and open (n = 12) conservative (organ preservation) surgery, i.e. open partial laryngectomy and cricotracheal resection and anastomoses. One patient underwent total laryngectomy 11 years after conservative surgery for recurrent symptomatic disease. Two patients died of unrelated causes. At last follow-up, seven patients were alive with asymptomatic stable disease and seven patients were alive without any evidence of persistent disease. The authors reported that all patients regained regular oral feeding and voice ranging from normal to moderate dysphonic after conservative surgery [39]. In high-grade chondrosarcomas, the surgical option is total laryngectomy. Given the low incidence of lymph node metastasis, (elective) neck dissection is not necessary [20, 40]. Tracheal chondrosarcomas can be managed with resection and end-to-end anastomosis [41]. Several reconstructions after partial laryngectomy for chondrosarcoma have been described: local flaps, autogenic rib implants and tracheal autotransplantation. Briefly, the two-stage procedure is as follows: During the first operation, extended hemilaryngectomy is performed, and a radial forearm flap is transferred to the neck, the fascial paddle being wrapped around the upper segment of cervical trachea and the skin paddle temporarily closing the surgical defect. Definitive reconstruction is undertaken after 2–3 months and consists of removal of the skin paddle and transplantation of a patch of re-vascularized cervical trachea to reconstruct the laryngeal defect. Delaere et al. [42] reported promising results in seven patients with chondrosarcoma of the cricoid cartilage with this technique.
In case of an asymptomatic low-grade lesion in a surgically difficult to access location, the optimal management is controversial. A conservative wait-and-see policy implementing CT scanning at regular time intervals can be considered, with surgery performed when the lesion grows and produces symptoms [7]. There are various views regarding the radiosensitivity of HNCS [43]. As this is a slowly growing tumor with a low fraction of dividing cells, it is considered as ‘‘relatively’’ radioresistant. It is generally accepted that the role of radiotherapy is for adjuvant treatment in cases of highly probable, residual disease after surgery, and for palliation in patients with unresectable lesions or unsuitable for major surgery [32, 44–46]. In low-grade chondrosarcomas with negative surgical margins, adjuvant radiotherapy is not indicated. In contrast, it is recommended in cases of highgrade chondrosarcoma due to the more aggressive behavior [47]. Prognosis is also improved in patients receiving adjuvant radiotherapy for histopathologically involved margins [32, 47, 48]. There are only case reports suggesting that radiotherapy alone can be successful, particularly in patients with laryngeal chondrosarcoma for whom total laryngectomy was the only surgical alternative [49, 50]. With the emergence of new types of radiotherapy such as intensity-modulated radiotherapy (IMRT), proton beam radiation or stereotactic fractionated radiotherapy, higher doses of radiation can be delivered and result in improved control rates for these tumors. Implementation of these new procedures in head and neck is of importance given the close proximity of vital structures [4, 51]. So far there is no convincing evidence that a particular procedure is clearly superior [32]. In skull-base chondrosarcomas, chargedparticle radiotherapy, specifically proton beam therapy, has gained favor over other radiotherapy modalities because of improved physical dose characteristics resulting in superior conformality and lower dose to adjacent structures. In series reporting the results of proton beam adjuvant therapy, substantially higher median irradiation doses were administered when compared to photon therapy, which ranged from 60 to 79 cobalt gray equivalent (CGE) [52]. In addition to proton beams, carbon-ion particle therapy has been successfully used for the treatment of skull-base chondrosarcomas. Carbon ions, having comparable physical characteristics to proton beams, also result in dosedistribution advantages in comparison with conventional photons and electrons. As high linear energy transfer (LET) beams, carbon ions also have a higher biological effectiveness than either protons or photons. In a series of 54 patients with skull-base chondrosarcomas treated with carbon ions, a tumor control rate of 89 % and an overall survival of 98 % at 5 years were reported [53]. The benefit of chemotherapy is negligible. Low-grade HNCSs seem to be chemoresistant, which possibly reflects
123
Eur Arch Otorhinolaryngol
their slow rate of growth with small fraction of proliferating cells, variable matrix and poor vascularization. Chemotherapy can be, however, used in high-grade chondrosarcomas, clinically aggressive tumors with rapid local recurrence and cases with a high probability of metastasis [54].
Prognosis Similar to other tumors, complete resection of HNCS significantly affects prognosis. Local recurrence is the main cause of death. Other factors influencing prognosis are stage at diagnosis, histopathological grade of the lesion (poor prognosis for high-grade tumors) and location. Particular histological subtypes, e.g. mesenchymal (see above), are more aggressive and show a poor prognosis [1, 47, 55]. In general, lymph node metastases are unusual (5 %) and distant metastases occur only in 7–18 %. However, high-grade chondrosarcomas may present with distant metastases in up to 71 % of cases [1, 54, 56]. Survival rates for HNCS range between 44 and 88 % [2, 19, 56–61]. Long-term follow-up is recommended because the tumors can give rise to local recurrence or even metastases many years after initial diagnosis.
Conclusion HNCS is a rare tumor––hence, it is difficult to establish an optimal treatment protocol. Surgery followed by adjuvant radiotherapy in cases with an increased risk of local recurrence is the treatment of choice. Conservative types of surgery should be considered for preservation of organs and function, depending on the site and grade of the tumor. Survival is generally good, but varying figures have been reported due to occurrence of aggressive histological types. Given the low incidence of HNCS and the complexity of the head and neck region, management should be ideally centralized in specialized centers with dedicated multidisciplinary teams.
References 1. Koch BB, Karnell LH, Hoffman HT et al (2000) National cancer database report on chondrosarcoma of the head and neck. Head Neck 22:408–425 2. Lee SY, Lim YC, Song MH et al (2005) Chondrosarcoma of the head and neck. Yonsei Med J 46:228–232 3. Fletcher CDM, Bridge JA, Hogendoorn PCW et al (2013) WHO classification of tumors of soft tissue and bone. IARC, Lyon 4. Neff B, Sataloff RT, Storey L et al (2002) Chondrosarcoma of the skull base. Laryngoscope 112:134–139
123
5. Sciubba JJ, Fantasia JE, Kahn LB (2001) Tumors and cysts of the jaws. Atlas of tumor pathology, fascicle 29, 3rd series. Armed Forces Institute of Pathology, Washington DC 6. Rosenberg A, Nielsen P, Keel SB et al (1999) Chondrosarcomas of the base of skull. Am J Surg Pathol 23:1370–1378 7. Lustig LR, Sciubba J, Holliday MJ (2007) Chondrosarcomas of the skull base and temporal bone. J Laryngol Otol 121:725–735 8. Helliwell TR (1999) Central cartilaginous neoplasms of bone. In: Helliwell TR (ed) Pathology of bone and joint neoplasms. Major problems in pathology, vol 37. Saunders, Philadelphia, pp 193–214 9. Eefting D, Schrage YM, Geirnaerdt MJ et al (2009) Assessment of interobserver variability and histologic parameters to improve reliability in classification and grading of central cartilaginous tumors. Am J Surg Pathol 33:50–57 10. Evans HL, Ayala AG, Romsdahl MM (1977) Prognostic factors in chondrosarcoma of bone: a clinicopathologic analysis with emphasis on histologic grading. Cancer 40:818–831 11. Giuffrida AY, Burgueno JE, Koniaris LG et al (2009) Chondrosarcoma in the United States (1973 to 2003): an analysis of 2890 cases from the SEER database. J Bone Joint Surg Am 91:1063–1072 12. Grimer RJ, Gosheger G, Taminiau A et al (2007) Dedifferentiated chondrosarcoma: prognostic factors and outcome from a European group. Eur J Cancer 43:2060–2065 13. Mitchell A, Scheithauer BW, Unni KK et al (1993) Chordoma and chondroid neoplasms of the spheno-occiput. An immunohistochemical study of 41 cases with prognostic and nosologic implications. Cancer 72:2943–2949 14. Vujovic S, Henderson S, Presneau N et al (2006) Brachyury, a crucial regulator of notochordal development, is a novel biomarker for chordomas. J Pathol 209:157–165 15. Huse JT, Pasha TL, Zhang PJ (2007) D2-40 functions as an effective chondroid marker distinguishing true chondroid tumors from chordoma. Acta Neuropathol 113:87–94 16. Weber A, Brown E, Hug E et al (1995) Cartilaginous tumors and chordomas of the cranial base. Otolaryngol Clin North Am 28:453–471 17. Hong P, Taylor MS, Trites JR et al (2009) Chondrosarcoma of the head and neck: report of 11 cases and literature review. J Otolaryngol Head Neck Surg 38:279–285 18. Knott PD, Gannon FH, Thompson LD (2003) Mesenchymal chondrosarcoma of the sinonasal tract: a clinicopathological study of 13 cases with a review of the literature. Laryngoscope 113:783–790 19. Obeso S, Llorente JL, Dı´az-Molina JP et al (2010) Surgical treatment of head and neck chondrosarcomas. Acta Otorrinolaryngol Esp 61:262–271 20. Buda I, Hod R, Feinmesser R et al (2012) Chondrosarcoma of the larynx. Isr Med Assoc J 14:681–684 21. Rinaldo A, Howard DJ, Ferlito A (2000) Laryngeal chondrosarcoma: a 24-year experience at the Royal National Throat, Nose and Ear Hospital. Acta Otolaryngol 120:680–688 22. Zhang I, Zaorsky N, Abraham J et al (2013) Chondrosarcoma of the hyoid bone: case report and a review of current management options. Head Neck. doi:10.1002/hed.23373 23. Al-Rawi M, Harper T, Bafakih F (2013) Chondrosarcoma of the tongue: a case report and a review of the literature. Laryngoscope 123:418–421 24. Gadwal SR, Fanburg-Smith JC, Gannon FH et al (2000) Primary chondrosarcoma of the head and neck in pediatric patients: a clinicopathologic study of 14 cases with a review of the literature. Cancer 88:2181–2188 25. Murphey MD, Walker EA, Wilson AJ et al (2003) From the archives of the AFIP: imaging of primary chondrosarcoma: radiologic-pathologic correlation. Radiographics 23:1245–1278
Eur Arch Otorhinolaryngol 26. Lee FY, Yu J, Chang SS et al (2004) Diagnostic value and limitations of fluorine-18 fluorodeoxyglucose positron emission tomography for cartilaginous tumors of bone. J Bone Joint Surg Am 86-A:2677–2685 27. Trembath DG, Dash R, Major NM et al (2003) Cytopathology of mesenchymal chondrosarcomas: a report and comparison of four patients. Cancer 99:211–216 28. Edge SB, Byrd DR, Compton CC et al (2010) American Joint Committee on Cancer Staging Manual, 7th edn. Springer, New York, p 281 29. Prado FO, Nishimoto IN, Perez DE et al (2009) Head and neck chondrosarcoma: analysis of 16 cases. Br J Oral Maxillofac Surg 47:555–557 30. Gardner P, Tormenti M, Pant H et al (2013) Carotid artery injury during endoscopic endonasal skull base surgery: incidence and outcomes. Neurosurgery [Epub ahead of print] 31. Wanebo JE, Bristol RE, Porter RR et al (2006) Management of cranial base chondrosarcomas. Neurosurgery 58:249–255 32. Bloch O, Parsa AT (2013) Skull base chondrosarcoma: evidencebased treatment paradigms. Neurosurg Clin North Am 24:89–96 33. Fernandez-Miranda JC, Gardner PA, Snyderman C et al (2013) Clival chordomas: a pathological, surgical and radiotherapeutic review. Head Neck. doi:10.1002/hed.23415 34. Fernandez-Miranda JC, Morera VA, Snyderman CH et al (2012) Endoscopic endonasal transclival approach to the jugular tubercle. Neurosurgery 71(1 Suppl Operative):146–159 35. Barges-Coll J, Fernandez-Miranda JC, Prevedello DM et al (2010) Avoiding injury to the abducens nerve during expanded endonasal endoscopic surgery: anatomic and clinical case studies. Neurosurgery 67:144–154 36. Morera VA, Fernandez-Miranda JC, Prevedello DM et al (2010) ‘‘Far-medial’’ expanded endonasal approach to the inferior third of the clivus: the transcondylar and transjugular tubercle approaches. Neurosurgery 66(6 Suppl Operative):211–219 37. Koutourousiou M, Gardner PA, Tormenti MJ et al (2012) Endoscopic endonasal approach for resection of skull base chordomas: outcomes and learning curve. Neurosurgery 71:614–625 38. Tiwari R, Mahieu H, Snow G (1999) Long-term results of organ preservation in chondrosarcoma of the cricoid. Eur Arch Otorhinolaryngol 256:271–276 39. Piazza C, Del Bon F, Grazioli P et al (2013) Organ preservation surgery for low- and intermediate-grade laryngeal chondrosarcomas: analysis of 16 cases. Laryngoscope. doi:10.1002/lary.24416 40. Jackson RS, Leon ME, McCaffrey TV (2013) Chondrosarcoma of the subglottic larynx: submucosal microdissection with the operating microscope. Laryngoscope 123:1216–1219 41. Umezu H, Tamura M, Kobayashi S et al (2008) Tracheal chondrosarcoma. Gen Thorac Cardiovasc Surg 56:199–202 42. Delaere PR, Vertriest R, Hermans R (2003) Functional treatment of a large laryngeal chondrosarcoma by tracheal autotransplantation. Ann Otol Rhinol Laryngol 112:678–682
43. Harwood AR, Cummings BJ, Fitzpatrick PJ (1984) Radiotherapy for unusual tumors of the head and neck. J Otolaryngol 13:391–394 44. Harwood AR, Krajbich JI, Fornasier VL (1980) Radiotherapy of chondrosarcoma of bone. Cancer 45:2769–2777 45. McNaney D, Lindberg RD, Ayala AG et al (1982) Fifteen year radiotherapy experience with chondrosarcoma of bone. Int J Radiat Oncol Biol Phys 8:187–190 46. Le A, Ball D, Pitman A et al (2003) Chondrosarcoma of bone complicating Ollier’s disease: report of a favourable response to radiotherapy. Australas Radiol 47:322–324 47. Bloch OG, Jian BJ, Yang I et al (2010) Cranial chondrosarcoma and recurrence: a systematic review. Skull Base 20:149–156 48. Fayda M, Aksu G, Yaman Agaoglu F et al (2009) The role of surgery and radiotherapy in treatment of soft tissue sarcomas of the head and neck region: review of 30 cases. J Craniomaxillofac Surg 37:42–48 49. Gripp S, Pape H, Schmitt G (1998) Chondrosarcoma of the larynx: the role of radiotherapy revisited––a case report and review of the literature. Cancer 82:108–115 50. Dailiana T, Nomikos P, Kapranos N et al (2002) Chondrosarcoma of the larynx: treatment with radiotherapy. Skeletal Radiol 31:547–549 51. Rutz HP, Weber DC, Goitein G et al (2008) Postoperative spotscanning proton radiation therapy for chordoma and chondrosarcoma in children and adolescents: initial experience at Paul Scherrer Institute. Int J Radiat Oncol Biol Phys 71:220–225 52. Fuji H, Nakasu Y, Ishida Y et al (2011) Feasibility of proton beam therapy for chordoma and chondrosarcoma of the skull base. Skull Base 21:201–206 53. Schulz-Ertner D, Nikoghosyan A, Hof H et al (2007) Carbon ion radiotherapy of skull base chondrosarcomas. Int J Radiat Oncol Biol Phys 67:171–177 54. Ruark DS, Schlehaider UK, Shah JP (1992) Chondrosarcomas of the head and neck. World J Surg 16:1010–1016 55. Pellitteri PK, Ferlito A, Fagan JJ et al (2007) Mesenchymal chondrosarcoma of the head and neck. Oral Oncol 43:970–975 56. Finn DG, Goepfert H, Batsakis JG (1984) Chondrosarcoma of the head and neck. Laryngoscope 94:1539–1544 57. Fo¨rander P, Ra¨hn T, Kihlstro¨m L et al (2006) Combination of microsurgery and gamma knife surgery for the treatment of intracranial chondrosarcomas. J Neurosurg 105:18–25 58. Arlen M, Toleefsen HF, Huvos AG et al (1970) Chondrosarcoma of head and neck. Am J Surg 120:456–460 59. Fu YS, Perzin KH (1974) Non-epithelial tumors of the nasal cavity, paranasal sinuses, and nasopharynx: a clinicopathologic study III. Cartilaginous tumors. Cancer 34:453–463 60. Khan MN, Husain Q, Kanumuri VV et al (2013) Management of sinonasal chondrosarcoma: a systematic review of 161 patients. Int Forum Allergy Rhinol 3:670–677 61. Damiani V, Crosetti E, Rizzotto G et al (2013) Well and intermediate differentiated laryngeal chondrosarcoma: toward conservative surgery? Eur Arch Otorhinolaryngol [Epub ahead of print]
123
