Eur Arch Otorhinolaryngol (2015) 272:765–772 DOI 10.1007/s00405-014-3419-2
CASE REPORT
Chondrosarcoma of the nasal septum Mauro Magnano • Paolo Boffano • Giacomo Machetta Elisabetta Garibaldi • Elena Delmastro • Pietro Gabriele
•
Received: 4 November 2014 / Accepted: 27 November 2014 / Published online: 2 December 2014 Ó Springer-Verlag Berlin Heidelberg 2014
Abstract Chondrosarcomas are non-epithelial malignant, slow growing tumors that usually involve pelvis, ribs, and long bones of extremities, scapula and sternum. Median age at diagnosis for head and neck chondrosarcomas is in the fourth decade. The etiopathogenesis of chondrosarcomas remains unknown. Treatment of choice is surgical, with adjuvant therapy having a limited role. In fact, radiation therapy and chemotherapy are reserved for residual or recurrent disease and palliation. As for surgery, several surgical procedures have been described. Recently, endoscopic surgery has allowed for the successful and less invasive treatment of inverting papillomas and even nasopharyngeal angiofibromas, lesions previously requiring extended external approaches. The aim of this paper was to present a case of nasal septal chondrosarcoma that was successfully treated with endoscopic surgery and radiation adjuvant therapy. Keywords Chondrosarcoma Nose Septum Tumor Treatment Cancer
M. Magnano G. Machetta Division of Otolaryngology, Pinerolo and Rivoli Hospitals, ASL TO3, Pinerolo, Italy P. Boffano (&) Private Practice, Turin, Italy e-mail: [email protected] E. Garibaldi E. Delmastro P. Gabriele Department of Radiotherapy, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - FPO, Candiolo, Turin, Italy
Introduction Chondrosarcomas are non-epithelial malignant, slow growing tumors that usually involve pelvis, ribs, and long bones of extremities, scapula and sternum [1–3]. Approximately only 5–10 % are located in the head and neck, arising rarely in the nasal septum [1–3]. Median age at diagnosis for head and neck chondrosarcomas is in the fourth decade [3]. The etiopathogenesis of chondrosarcomas remains unknown [4]. However, in the head and neck region, chondrosarcomas are thought to arise from the cartilaginous remnants of the petroclival, spheno-occipital, and frontonasal synchondroses, although they also have been known to arise from tissues that do not normally harbor cartilage [5]. Therefore, chondrosarcomas seem to arise from primitive mesenchymal stem cells or may also arise from tissue not ordinarily containing cartilage (dura, falx, maxilla) because of multidirectional differentiation of mesenchymal cell [1]. In particular, chondrosarcomas have been classified into three main types: primary chondrosarcomas (arising from undifferentiated perichondrial cells), secondary chondrosarcomas (arising from altered cells either in a central chondroma or cartilaginous exostosis), and mesenchymal chondrosarcomas (arising from primitive mesenchymal cells) [3]. Associated conditions such as multiple hereditary exostosis, Ollier’s disease, Maffucci’s syndrome, previous intravenous thorium dioxide contrast use, Paget’s disease of bone, chondromyxoid fibroma, and previous irradiation have been reported [3, 4]. Treatment of choice is surgical, with adjuvant therapy having a limited role. In fact, radiation therapy and chemotherapy are reserved for residual or recurrent disease and palliation [2, 3]. As for surgery, several surgical procedures have been described, including a Weber–Ferguson
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approach, sublabial transnasal approach, lateral rhinotomy approach, anterior craniofacial resection, and Le Fort I downfracture. Recently, endoscopic surgery has allowed for the successful and less invasive treatment of inverting papillomas and even nasopharyngeal angiofibromas, lesions previously requiring extended external approaches [2]. The aim of this paper was to present a case of nasal septal chondrosarcoma that was successfully treated with endoscopic surgery and radiation adjuvant therapy.
Case report A 41-year-old female patient presented to our hospital complaining pain, lachrymation, and conjuntival hyperemia in correspondence of the right eye of 2 weeks duration. There was no history of epistaxis or visual disturbance. On clinical examination, the exophthalmos of
Fig. 1 Nasal endoscopy revealing firm smooth surfaced mass arising from the septum, extending into the nasal cavities bilaterally. a Right nasal fossa, b left nasal fossa
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Eur Arch Otorhinolaryngol (2015) 272:765–772 Fig. 2 Preoperative magnetic resonance imaging (MRI) revealing ac nasal mass with obstruction of the right and left nasal fossae, with extension across the midline and erosion of the nasal septum. The mass presents low intensity on T1 images, high intensity on T2 images, and heterogeneous enhancement after gadolinium infusion with higher enhancement in the peripheral areas of the mass with lower enhancement in the central area. a T1-weighted Fast Field Echo axial scan, b T2-weighted Fast Field Echo axial scan, c T1-weighted Fast Field Echo axial scan after gadolinium infusion, d T1-weighted Turbo Spin Echo axial scan, e T1-weighted Turbo Spin Echo coronal scan, f T2-weighted Turbo Spin Echo axial scan
the right eye could be observed. Nasal endoscopy revealed firm smooth surfaced mass arising from the septum, extending into the nasal cavities bilaterally (Fig. 1a, b). There was no palpable neck node and the rest of head and neck examinations were unremarkable. Magnetic resonance imaging (MRI) revealed a nasal mass with obstruction of the right and left nasal cavities, with extension across the midline and erosion of the nasal septum (Fig. 2). The lesion showed low intensity on T1 images, high intensity on T2 images, and inhomogeneous enhancement after gadolinium infusion with higher enhancement in the peripheral areas of the mass with lower enhancement in the central area. There was no evidence of intracranial extension. Multiple biopsies by endoscopy were performed with the subsequent histological findings consistent with the diagnosis of grade I–II chondrosarcoma. Therefore, the patient underwent the surgical removal of the mass by endoscopy under general anesthesia. A large mass was found arising from the septum occupying the entire nasal cavity bilaterally. The resection was macroscopically radical. The mucosa of the maxillary sinuses was normal. Postoperative course was uneventful. Definitive histopathological examination of the excised specimen confirmed the preoperative diagnosis of grade I– II chondrosarcoma of the nasal septum. In particular, lobules of neoplastic chondrocytes set in a cartilaginous matrix were identified, together with hyperchromatism, occasional mitotic figures and multinucleation. Furthermore, a small foci of well-differentiated chondrosarcoma was identified in proximity of the posterosuperior margin of resection, although a free-of-disease margin could still be appreciated. Following a multidisciplinary oncologic meeting, a radiation treatment was suggested. Patient was referred to a Proton Therapy Italian Centre for evaluation, but no indication for this kind of radiotherapy was given. Also an Intensity Modulated Radiation Therapy (IMRT) technique by LINAC Varian 600 was evaluated without success. Therefore, the patient was referred to IRCCS Centre, in Candiolo (Turin) to evaluate an helical IMRT technique with daily Image Guidance (IGRT), by Tomotherapy @Hi
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Art. Before the treatment planning, MRI was performed to evaluate possible local persistence/recurrence. The MRI revealed an uncertain area at the level of the roof of the nasal septum and at the level of the base of the surgical cavity. Then a CT-virtual simulation scan for treatment planning was acquired with slices of 3 mm from the vertex until jugular notch. On the CT images, the target volumes (PTV) were contoured as follows: the PTV nasal cavity where a total dose of 54 Gy in 30 fractions was prescribed, in fractions of 1.8 Gy; the PTV risk area, as shown by MRI, where a total dose of 63.5 Gy in 30 fraction at 2.1 Gy per fraction (including two fractions of 2.35 Gy). On CT-
Fig. 3 Helical IMRT treatment planning by Tomotherapy, showing isodoses: in red the 63.5 Gy isodose on the roof of the nasal cavity indicated by MRI as suspected area, in green the 54 Gy isodose. In figure a and c axial images, in b coronal image and in c sagittal image
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virtual simulation also all organs at risk were countered, including eyes, optical nerves, optic chiasm, lens, brain, brainstem, spinal cord, parotid glands, inner ear. The prescription doses and doses to organ at risk were evaluated according to QUANTEC document. Treatment planning with Tomotherapy was satisfactory due to very high conformation of helical IMRT technique allowing to spare critical organ at risk in close proximity of the target volume (Fig. 3), as shown by dose-volume histograms (Fig. 4). The treatment was well tolerated with a mucosal and skin acute toxicity of G 1 grade according to RTOG-EORTC scale.
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Fig. 4 Dose-volume histogram of the dose to the target volume and organs at risk
Two years follow-up after surgery and radiation therapy, endoscopy clinical examinations (Fig. 5) and RM scans (Fig. 6) did not reveal any evidence recurrent disease.
Discussion
Fig. 5 a, b Endoscopic images confirming the clinical absence of recurrences at follow-up
The history and clinical features of this entity are variable and non-specific, making it difficult to assign a clinical diagnosis [5]. The presenting symptoms of chondrosarcomas are related to their size and site, keeping in mind that they are often large at the initial presentation [3]. In fact, chondrosarcomas of the nasal septum may present with a variety of symptoms, such as nasal obstruction, epistaxis, chronic nasal discharge, headache, or even proptosis or lachrymation. Our patient referred pain, lachrymation, and conjuntival hyperemia, and she also presented exophthalmos of the right eye, thus confirming the importance of eye symptoms to suspect this disease. Imaging is essential to evaluate the bone and soft-tissue characteristics of the tumor, as well as to perform an appropriate preoperative planning [5]. Chondrosarcomas demonstrate characteristic findings on both CT and MRI [2]. On CT scan, chondrosarcomas of the nasal septum typically show a hypoattenuating matrix with scattered small calcifications, occasional large or ring-like calcifications, and associated erosion of the septum and surrounding bony structures [3]. However, in some cases CT may not accurately reveal the full extent of disease present. For this reason, MR imaging may be preferred in the
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Fig. 6 Postoperative MRI performed after 2 years of follow-up revealing the absence of recurrence in the nasal cavity. a T1-weighted Turbo Spin Echo axial scan, b T1-weighted Turbo Spin Echo coronal
scan, c T2-weighted Turbo Spin Echo axial scan, d T2-weighted Turbo Spin Echo coronal scan
staging of disease as it may allow a better definition of the neoplastic mass. On MR imaging, chondrosarcomas typically appear as low signal intensity mass on T1-weighted imaging, and as a high signal intensity lesion on T2weighted imaging, with heterogeneous enhancement after the administration of intravenous gadolinium [4, 6]. Furthermore, chondrosarcomas of the nasal septum commonly present symmetrical growth into both sides of the nasal cavity, although confirming the nasal septum as the epicenter of the chondrosarcoma may be difficult with imaging. To this aim, correlation with intraoperative findings is crucial to determine the site of origin [3]. Preoperative MR imaging of our patient confirmed the typical features of nasal septum chondrosarcomas as reported in the literature, thus facilitating us with the diagnosis and operative planning.
Histologically, the criteria for the proper diagnosis of this neoplasm are the presence of many cells with hyperchromatic nuclei, two or more such chondrocytes within a lacuna and giant cartilage cells with large single or multiple nuclei with clumps of chromatin and mitotic activity [1]. Chondrosarcomas may be classified into three grades on the basis of the degree of cellularity, nuclear size and atypia, and mitotic activity [2, 3]. Grade 1 chondrosarcomas present abundant chondroid matrix, clusters of chondrocytes with normal or slightly irregular nuclei, rare nucleoli, absence of mitoses, and occasional binucleation. Grade 2 chondrosarcomas exhibit less chondroid matrix and more chondrocytes than grade I tumors, presence of rare mitoses, slightly enlarged vesicular hyperchromatic nuclei, and multinucleation. Finally, grade 3 tumors display high cellularity, a myxoid matrix with irregularly shaped
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chondrocytes, prominent nuclear pleomorphism, and increased mitoses compared with the low-grade chondrosarcomas [2, 3]. The clinical and radiological differential diagnosis of nasal septum chondrosarcomas includes chondroma, meningioma, osteomas, osteoblastomas, osteosarcomas, fibro-osseous lesions and chordoma [3]. On CT scan, bony erosion is absent in chondromas, osteoblastomas, and osteochondromas. Meningiomas produce hyperostosis rather than scattered calcifications and are isointense on MRI T2 images. Osteosarcomas produce linear calcifications in the classic ‘‘sunray’’ pattern instead of the spotty calcifications of chondrosarcomas seen on CT scanning [3]. Histologically, chondrosarcomas have to be differentiated from chondroma, chondroid chordoma, osteogenic sarcoma and salivary gland neoplasm. In particular, chondromas may be difficult to be differentiated from chondrosarcomas [3]. Chondromas are made up of islands of hyaline cartilage enclosed within a vascularized fibrous stroma with irregularly displaced chondrocytes throughout the matrix, whereas multinucleated cells or marked cellular dysplasia are unusual. Instead, chondroid chordomas display sheets and cords of epithelial cells surrounded by a mucinous matrix [3]. The performance of a biopsy is crucial to obtain a confirmed diagnosis before surgery. Surgery is the treatment of choice for head and neck chondrosarcomas with radiation therapy or chemotherapy used for adjuvant treatment, residual or recurrent disease, and palliation [3]. In addition to the recently reported endoscopy, the following surgical approaches have been mentioned in the literature: Weber–Ferguson, lateral rhinotomy, sublabial transnasal, Le Fort I downfracture, anterior craniofacial approach, and transnasal excision [3]. The goal of all types of surgery is histologically clear margins. In our case, endoscopic excision allowed clear margins although small foci of well-differentiated chondrosarcoma were identified in proximity of the three margins of resection. However, after radiation therapy, excellent local control was obtained with no recurrence after 2 years follow-up. In fact, radiation therapy studies have shown excellent local control and actuarial survival rates with skull base chondrosarcomas after surgical debulking. In a recently published study about head and neck chondrosarcomas, the authors conclude that surgery alone or followed by adjuvant radiotherapy is the treatment of choice. Radiotherapy alone has also been reported to be 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 [7].
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A recent review evaluated a total of 63 journal articles, comprising a total of 161 cases of sinonasal chondrosarcoma. Surgical resection was the most common treatment modality used in 72.0 % of cases. A combination of surgery and radiation therapy was the second most commonly used treatment modality used in 21.7 % of cases. This review contains the largest pool of sinonasal chondrosarcoma patients to date and suggests that aggressive surgical resection is the most common treatment modality for this condition. The use of adjuvant radiotherapy for prevention of local recurrence after subtotal or total resection has not been proven effective. However, the use of radiotherapy in addition to surgical resection has shown benefit in some studies in terms of survival [8]. Since an aggressive local radiotherapy in the proximity of critical normal structures in the head and neck area is very difficult and may produce debilitating early and late toxicity, special techniques have to be used to improve results. Specifically the proton therapy showed improvements in local control outcomes for patients with chordoma, chondrosarcoma, and tumors in the sinonasal regions have been reported in published series [9]. In the Heidelberg ion therapy center, a total of 118 patients, including skull base chordomas and chondrosarcomas, salivary gland tumors, and gliomas were treated with proton and carbon ion radiotherapy (RT). Early toxicity and the initial clinical and radiologic response were evaluated. No severe acute toxicity was observed in all patients. For skull base tumors, imaging showed a stable tumor outline in most patients. Thirteen patients showed improvement of pre-existing clinical symptoms. The authors conclude that side effects related to particle treatment were rare and the initial response was promising [10]. Therefore, radiotherapy or chemotherapy may be used for adjuvant treatment in case of residual disease, those extending to vital structure that impeded wide resection, recurrent disease and for palliation [3]. In our opinion, lesions limited to the nasal cavity, without evidence of intracranial or skull base extension, may be treated by endoscopic surgery, that allow to spare the potential morbidity of more aggressive open procedures. Furthermore, by not disrupting the anterior facial skeleton, normal anatomic relationships are maintained and normal sinonasal functioning can be expected after the initial period of healing, with obvious cosmetic and esthetic benefits. Anyway, a more aggressive surgical approach may still be considered either for a primary presentation or for cases of recurrence [2]. The prognosis of nasal septum chondrosarcomas mainly depends on the location and size of the tumor, and the degree of differentiation [1]. Overall survival at 5 year for all grades combined is approximately 44–81 % [3]. About
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7–20 % of the patients develop distant metastasis, mainly in lungs and bones [3, 4]. However, uncontrollable local disease is the most frequent cause of death [4]. In conclusion, though rare, nasal septal chondrosarcomas have to be considered in the differential diagnosis of midline nasal masses. MRI is crucial in establishing a correct diagnosis before biopsy and removal of endoscopic resection of nasal septal chondrosarcoma is a viable approach to treating this lesion when significant skull base invasion or intracranial extension is absent, thus avoiding the morbidity of the more commonly used open approaches. Conflict of interest
Nothing to disclose.
References 1. Ali A, Gosavi M, Michael R, Mathew J, Kurien M, Korula A (2004) Chondrosarcoma of the nasal septum. Indian J Otolaryngol Head Neck Surg 56(4):314–316 2. Coppit GL, Eusterman VD, Bartels J, Downey TJ (2002) Endoscopic resection of chondrosarcomas of the nasal septum: a report of two cases. Otolaryngol Head Neck Surg 127(6):569–571
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3. Downey TJ, Clark SK, Moore DW (2001) Chondrosarcoma of the nasal septum. Otolaryngol Head Neck Surg 125(1):98–100 4. Kainuma K, Netsu K, Asamura K, Hayashi K, Takumi Y, Ota H, Usami S (2009) Chondrosarcoma of the nasal septum: a case report. Auris Nasus Larynx 36(5):601–605 5. Dass AN, Peh WC, Shek TW, Ho WK (2008) Case 139: nasal septum low-grade chondrosarcoma. Radiology 249(2):714–717 6. Yamamoto S, Motoori K, Takano H, Nagata H, Ueda T, Osaka I (2002) Chondrosarcoma of the nasal septum. Skeletal Radiol 31(9):543–546 7. Coca-Pelaz A, Rodrigo JP, Triantafyllou A, Hunt JL, Ferna´ndezMiranda JC, Strojan P, de Bree R, Rinaldo A, Takes RP, Ferlito A (2014) Chondrosarcomas of the head and neck. Eur Arch Otorhinolaryngol 271(10):2601–2609 8. Khan MN, Husain Q, Kanumuri VV, Boghani Z, Patel CR, Liu JK, Eloy JA (2013) Management of sinonasal chondrosarcoma: a systematic review of 161 patients. Int Forum Allergy Rhinol 3(8):670–677 9. Holliday EB, Frank SJ (2014) Proton radiation therapy for head and neck cancer: a review of the clinical experience to date. Int J Radiat Oncol Biol Phys 89(2):292–302 10. Rieken S, Habermehl D, Nikoghosyan A, Jensen A, Haberer T, Ja¨kel O, Mu¨nter MW, Welzel T, Debus J, Combs SE (2011) Assessment of early toxicity and response in patients treated with proton and carbon ion therapy at the Heidelberg ion therapy center using the raster scanning technique. Int J Radiat Oncol Biol Phys 81(5):e793–e801
CASE REPORT
Chondrosarcoma of the nasal septum Mauro Magnano • Paolo Boffano • Giacomo Machetta Elisabetta Garibaldi • Elena Delmastro • Pietro Gabriele
•
Received: 4 November 2014 / Accepted: 27 November 2014 / Published online: 2 December 2014 Ó Springer-Verlag Berlin Heidelberg 2014
Abstract Chondrosarcomas are non-epithelial malignant, slow growing tumors that usually involve pelvis, ribs, and long bones of extremities, scapula and sternum. Median age at diagnosis for head and neck chondrosarcomas is in the fourth decade. The etiopathogenesis of chondrosarcomas remains unknown. Treatment of choice is surgical, with adjuvant therapy having a limited role. In fact, radiation therapy and chemotherapy are reserved for residual or recurrent disease and palliation. As for surgery, several surgical procedures have been described. Recently, endoscopic surgery has allowed for the successful and less invasive treatment of inverting papillomas and even nasopharyngeal angiofibromas, lesions previously requiring extended external approaches. The aim of this paper was to present a case of nasal septal chondrosarcoma that was successfully treated with endoscopic surgery and radiation adjuvant therapy. Keywords Chondrosarcoma Nose Septum Tumor Treatment Cancer
M. Magnano G. Machetta Division of Otolaryngology, Pinerolo and Rivoli Hospitals, ASL TO3, Pinerolo, Italy P. Boffano (&) Private Practice, Turin, Italy e-mail: [email protected] E. Garibaldi E. Delmastro P. Gabriele Department of Radiotherapy, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - FPO, Candiolo, Turin, Italy
Introduction Chondrosarcomas are non-epithelial malignant, slow growing tumors that usually involve pelvis, ribs, and long bones of extremities, scapula and sternum [1–3]. Approximately only 5–10 % are located in the head and neck, arising rarely in the nasal septum [1–3]. Median age at diagnosis for head and neck chondrosarcomas is in the fourth decade [3]. The etiopathogenesis of chondrosarcomas remains unknown [4]. However, in the head and neck region, chondrosarcomas are thought to arise from the cartilaginous remnants of the petroclival, spheno-occipital, and frontonasal synchondroses, although they also have been known to arise from tissues that do not normally harbor cartilage [5]. Therefore, chondrosarcomas seem to arise from primitive mesenchymal stem cells or may also arise from tissue not ordinarily containing cartilage (dura, falx, maxilla) because of multidirectional differentiation of mesenchymal cell [1]. In particular, chondrosarcomas have been classified into three main types: primary chondrosarcomas (arising from undifferentiated perichondrial cells), secondary chondrosarcomas (arising from altered cells either in a central chondroma or cartilaginous exostosis), and mesenchymal chondrosarcomas (arising from primitive mesenchymal cells) [3]. Associated conditions such as multiple hereditary exostosis, Ollier’s disease, Maffucci’s syndrome, previous intravenous thorium dioxide contrast use, Paget’s disease of bone, chondromyxoid fibroma, and previous irradiation have been reported [3, 4]. Treatment of choice is surgical, with adjuvant therapy having a limited role. In fact, radiation therapy and chemotherapy are reserved for residual or recurrent disease and palliation [2, 3]. As for surgery, several surgical procedures have been described, including a Weber–Ferguson
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approach, sublabial transnasal approach, lateral rhinotomy approach, anterior craniofacial resection, and Le Fort I downfracture. Recently, endoscopic surgery has allowed for the successful and less invasive treatment of inverting papillomas and even nasopharyngeal angiofibromas, lesions previously requiring extended external approaches [2]. The aim of this paper was to present a case of nasal septal chondrosarcoma that was successfully treated with endoscopic surgery and radiation adjuvant therapy.
Case report A 41-year-old female patient presented to our hospital complaining pain, lachrymation, and conjuntival hyperemia in correspondence of the right eye of 2 weeks duration. There was no history of epistaxis or visual disturbance. On clinical examination, the exophthalmos of
Fig. 1 Nasal endoscopy revealing firm smooth surfaced mass arising from the septum, extending into the nasal cavities bilaterally. a Right nasal fossa, b left nasal fossa
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Eur Arch Otorhinolaryngol (2015) 272:765–772 Fig. 2 Preoperative magnetic resonance imaging (MRI) revealing ac nasal mass with obstruction of the right and left nasal fossae, with extension across the midline and erosion of the nasal septum. The mass presents low intensity on T1 images, high intensity on T2 images, and heterogeneous enhancement after gadolinium infusion with higher enhancement in the peripheral areas of the mass with lower enhancement in the central area. a T1-weighted Fast Field Echo axial scan, b T2-weighted Fast Field Echo axial scan, c T1-weighted Fast Field Echo axial scan after gadolinium infusion, d T1-weighted Turbo Spin Echo axial scan, e T1-weighted Turbo Spin Echo coronal scan, f T2-weighted Turbo Spin Echo axial scan
the right eye could be observed. Nasal endoscopy revealed firm smooth surfaced mass arising from the septum, extending into the nasal cavities bilaterally (Fig. 1a, b). There was no palpable neck node and the rest of head and neck examinations were unremarkable. Magnetic resonance imaging (MRI) revealed a nasal mass with obstruction of the right and left nasal cavities, with extension across the midline and erosion of the nasal septum (Fig. 2). The lesion showed low intensity on T1 images, high intensity on T2 images, and inhomogeneous enhancement after gadolinium infusion with higher enhancement in the peripheral areas of the mass with lower enhancement in the central area. There was no evidence of intracranial extension. Multiple biopsies by endoscopy were performed with the subsequent histological findings consistent with the diagnosis of grade I–II chondrosarcoma. Therefore, the patient underwent the surgical removal of the mass by endoscopy under general anesthesia. A large mass was found arising from the septum occupying the entire nasal cavity bilaterally. The resection was macroscopically radical. The mucosa of the maxillary sinuses was normal. Postoperative course was uneventful. Definitive histopathological examination of the excised specimen confirmed the preoperative diagnosis of grade I– II chondrosarcoma of the nasal septum. In particular, lobules of neoplastic chondrocytes set in a cartilaginous matrix were identified, together with hyperchromatism, occasional mitotic figures and multinucleation. Furthermore, a small foci of well-differentiated chondrosarcoma was identified in proximity of the posterosuperior margin of resection, although a free-of-disease margin could still be appreciated. Following a multidisciplinary oncologic meeting, a radiation treatment was suggested. Patient was referred to a Proton Therapy Italian Centre for evaluation, but no indication for this kind of radiotherapy was given. Also an Intensity Modulated Radiation Therapy (IMRT) technique by LINAC Varian 600 was evaluated without success. Therefore, the patient was referred to IRCCS Centre, in Candiolo (Turin) to evaluate an helical IMRT technique with daily Image Guidance (IGRT), by Tomotherapy @Hi
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Art. Before the treatment planning, MRI was performed to evaluate possible local persistence/recurrence. The MRI revealed an uncertain area at the level of the roof of the nasal septum and at the level of the base of the surgical cavity. Then a CT-virtual simulation scan for treatment planning was acquired with slices of 3 mm from the vertex until jugular notch. On the CT images, the target volumes (PTV) were contoured as follows: the PTV nasal cavity where a total dose of 54 Gy in 30 fractions was prescribed, in fractions of 1.8 Gy; the PTV risk area, as shown by MRI, where a total dose of 63.5 Gy in 30 fraction at 2.1 Gy per fraction (including two fractions of 2.35 Gy). On CT-
Fig. 3 Helical IMRT treatment planning by Tomotherapy, showing isodoses: in red the 63.5 Gy isodose on the roof of the nasal cavity indicated by MRI as suspected area, in green the 54 Gy isodose. In figure a and c axial images, in b coronal image and in c sagittal image
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virtual simulation also all organs at risk were countered, including eyes, optical nerves, optic chiasm, lens, brain, brainstem, spinal cord, parotid glands, inner ear. The prescription doses and doses to organ at risk were evaluated according to QUANTEC document. Treatment planning with Tomotherapy was satisfactory due to very high conformation of helical IMRT technique allowing to spare critical organ at risk in close proximity of the target volume (Fig. 3), as shown by dose-volume histograms (Fig. 4). The treatment was well tolerated with a mucosal and skin acute toxicity of G 1 grade according to RTOG-EORTC scale.
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Fig. 4 Dose-volume histogram of the dose to the target volume and organs at risk
Two years follow-up after surgery and radiation therapy, endoscopy clinical examinations (Fig. 5) and RM scans (Fig. 6) did not reveal any evidence recurrent disease.
Discussion
Fig. 5 a, b Endoscopic images confirming the clinical absence of recurrences at follow-up
The history and clinical features of this entity are variable and non-specific, making it difficult to assign a clinical diagnosis [5]. The presenting symptoms of chondrosarcomas are related to their size and site, keeping in mind that they are often large at the initial presentation [3]. In fact, chondrosarcomas of the nasal septum may present with a variety of symptoms, such as nasal obstruction, epistaxis, chronic nasal discharge, headache, or even proptosis or lachrymation. Our patient referred pain, lachrymation, and conjuntival hyperemia, and she also presented exophthalmos of the right eye, thus confirming the importance of eye symptoms to suspect this disease. Imaging is essential to evaluate the bone and soft-tissue characteristics of the tumor, as well as to perform an appropriate preoperative planning [5]. Chondrosarcomas demonstrate characteristic findings on both CT and MRI [2]. On CT scan, chondrosarcomas of the nasal septum typically show a hypoattenuating matrix with scattered small calcifications, occasional large or ring-like calcifications, and associated erosion of the septum and surrounding bony structures [3]. However, in some cases CT may not accurately reveal the full extent of disease present. For this reason, MR imaging may be preferred in the
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Fig. 6 Postoperative MRI performed after 2 years of follow-up revealing the absence of recurrence in the nasal cavity. a T1-weighted Turbo Spin Echo axial scan, b T1-weighted Turbo Spin Echo coronal
scan, c T2-weighted Turbo Spin Echo axial scan, d T2-weighted Turbo Spin Echo coronal scan
staging of disease as it may allow a better definition of the neoplastic mass. On MR imaging, chondrosarcomas typically appear as low signal intensity mass on T1-weighted imaging, and as a high signal intensity lesion on T2weighted imaging, with heterogeneous enhancement after the administration of intravenous gadolinium [4, 6]. Furthermore, chondrosarcomas of the nasal septum commonly present symmetrical growth into both sides of the nasal cavity, although confirming the nasal septum as the epicenter of the chondrosarcoma may be difficult with imaging. To this aim, correlation with intraoperative findings is crucial to determine the site of origin [3]. Preoperative MR imaging of our patient confirmed the typical features of nasal septum chondrosarcomas as reported in the literature, thus facilitating us with the diagnosis and operative planning.
Histologically, the criteria for the proper diagnosis of this neoplasm are the presence of many cells with hyperchromatic nuclei, two or more such chondrocytes within a lacuna and giant cartilage cells with large single or multiple nuclei with clumps of chromatin and mitotic activity [1]. Chondrosarcomas may be classified into three grades on the basis of the degree of cellularity, nuclear size and atypia, and mitotic activity [2, 3]. Grade 1 chondrosarcomas present abundant chondroid matrix, clusters of chondrocytes with normal or slightly irregular nuclei, rare nucleoli, absence of mitoses, and occasional binucleation. Grade 2 chondrosarcomas exhibit less chondroid matrix and more chondrocytes than grade I tumors, presence of rare mitoses, slightly enlarged vesicular hyperchromatic nuclei, and multinucleation. Finally, grade 3 tumors display high cellularity, a myxoid matrix with irregularly shaped
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chondrocytes, prominent nuclear pleomorphism, and increased mitoses compared with the low-grade chondrosarcomas [2, 3]. The clinical and radiological differential diagnosis of nasal septum chondrosarcomas includes chondroma, meningioma, osteomas, osteoblastomas, osteosarcomas, fibro-osseous lesions and chordoma [3]. On CT scan, bony erosion is absent in chondromas, osteoblastomas, and osteochondromas. Meningiomas produce hyperostosis rather than scattered calcifications and are isointense on MRI T2 images. Osteosarcomas produce linear calcifications in the classic ‘‘sunray’’ pattern instead of the spotty calcifications of chondrosarcomas seen on CT scanning [3]. Histologically, chondrosarcomas have to be differentiated from chondroma, chondroid chordoma, osteogenic sarcoma and salivary gland neoplasm. In particular, chondromas may be difficult to be differentiated from chondrosarcomas [3]. Chondromas are made up of islands of hyaline cartilage enclosed within a vascularized fibrous stroma with irregularly displaced chondrocytes throughout the matrix, whereas multinucleated cells or marked cellular dysplasia are unusual. Instead, chondroid chordomas display sheets and cords of epithelial cells surrounded by a mucinous matrix [3]. The performance of a biopsy is crucial to obtain a confirmed diagnosis before surgery. Surgery is the treatment of choice for head and neck chondrosarcomas with radiation therapy or chemotherapy used for adjuvant treatment, residual or recurrent disease, and palliation [3]. In addition to the recently reported endoscopy, the following surgical approaches have been mentioned in the literature: Weber–Ferguson, lateral rhinotomy, sublabial transnasal, Le Fort I downfracture, anterior craniofacial approach, and transnasal excision [3]. The goal of all types of surgery is histologically clear margins. In our case, endoscopic excision allowed clear margins although small foci of well-differentiated chondrosarcoma were identified in proximity of the three margins of resection. However, after radiation therapy, excellent local control was obtained with no recurrence after 2 years follow-up. In fact, radiation therapy studies have shown excellent local control and actuarial survival rates with skull base chondrosarcomas after surgical debulking. In a recently published study about head and neck chondrosarcomas, the authors conclude that surgery alone or followed by adjuvant radiotherapy is the treatment of choice. Radiotherapy alone has also been reported to be 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 [7].
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A recent review evaluated a total of 63 journal articles, comprising a total of 161 cases of sinonasal chondrosarcoma. Surgical resection was the most common treatment modality used in 72.0 % of cases. A combination of surgery and radiation therapy was the second most commonly used treatment modality used in 21.7 % of cases. This review contains the largest pool of sinonasal chondrosarcoma patients to date and suggests that aggressive surgical resection is the most common treatment modality for this condition. The use of adjuvant radiotherapy for prevention of local recurrence after subtotal or total resection has not been proven effective. However, the use of radiotherapy in addition to surgical resection has shown benefit in some studies in terms of survival [8]. Since an aggressive local radiotherapy in the proximity of critical normal structures in the head and neck area is very difficult and may produce debilitating early and late toxicity, special techniques have to be used to improve results. Specifically the proton therapy showed improvements in local control outcomes for patients with chordoma, chondrosarcoma, and tumors in the sinonasal regions have been reported in published series [9]. In the Heidelberg ion therapy center, a total of 118 patients, including skull base chordomas and chondrosarcomas, salivary gland tumors, and gliomas were treated with proton and carbon ion radiotherapy (RT). Early toxicity and the initial clinical and radiologic response were evaluated. No severe acute toxicity was observed in all patients. For skull base tumors, imaging showed a stable tumor outline in most patients. Thirteen patients showed improvement of pre-existing clinical symptoms. The authors conclude that side effects related to particle treatment were rare and the initial response was promising [10]. Therefore, radiotherapy or chemotherapy may be used for adjuvant treatment in case of residual disease, those extending to vital structure that impeded wide resection, recurrent disease and for palliation [3]. In our opinion, lesions limited to the nasal cavity, without evidence of intracranial or skull base extension, may be treated by endoscopic surgery, that allow to spare the potential morbidity of more aggressive open procedures. Furthermore, by not disrupting the anterior facial skeleton, normal anatomic relationships are maintained and normal sinonasal functioning can be expected after the initial period of healing, with obvious cosmetic and esthetic benefits. Anyway, a more aggressive surgical approach may still be considered either for a primary presentation or for cases of recurrence [2]. The prognosis of nasal septum chondrosarcomas mainly depends on the location and size of the tumor, and the degree of differentiation [1]. Overall survival at 5 year for all grades combined is approximately 44–81 % [3]. About
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7–20 % of the patients develop distant metastasis, mainly in lungs and bones [3, 4]. However, uncontrollable local disease is the most frequent cause of death [4]. In conclusion, though rare, nasal septal chondrosarcomas have to be considered in the differential diagnosis of midline nasal masses. MRI is crucial in establishing a correct diagnosis before biopsy and removal of endoscopic resection of nasal septal chondrosarcoma is a viable approach to treating this lesion when significant skull base invasion or intracranial extension is absent, thus avoiding the morbidity of the more commonly used open approaches. Conflict of interest
Nothing to disclose.
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3. Downey TJ, Clark SK, Moore DW (2001) Chondrosarcoma of the nasal septum. Otolaryngol Head Neck Surg 125(1):98–100 4. Kainuma K, Netsu K, Asamura K, Hayashi K, Takumi Y, Ota H, Usami S (2009) Chondrosarcoma of the nasal septum: a case report. Auris Nasus Larynx 36(5):601–605 5. Dass AN, Peh WC, Shek TW, Ho WK (2008) Case 139: nasal septum low-grade chondrosarcoma. Radiology 249(2):714–717 6. Yamamoto S, Motoori K, Takano H, Nagata H, Ueda T, Osaka I (2002) Chondrosarcoma of the nasal septum. Skeletal Radiol 31(9):543–546 7. Coca-Pelaz A, Rodrigo JP, Triantafyllou A, Hunt JL, Ferna´ndezMiranda JC, Strojan P, de Bree R, Rinaldo A, Takes RP, Ferlito A (2014) Chondrosarcomas of the head and neck. Eur Arch Otorhinolaryngol 271(10):2601–2609 8. Khan MN, Husain Q, Kanumuri VV, Boghani Z, Patel CR, Liu JK, Eloy JA (2013) Management of sinonasal chondrosarcoma: a systematic review of 161 patients. Int Forum Allergy Rhinol 3(8):670–677 9. Holliday EB, Frank SJ (2014) Proton radiation therapy for head and neck cancer: a review of the clinical experience to date. Int J Radiat Oncol Biol Phys 89(2):292–302 10. Rieken S, Habermehl D, Nikoghosyan A, Jensen A, Haberer T, Ja¨kel O, Mu¨nter MW, Welzel T, Debus J, Combs SE (2011) Assessment of early toxicity and response in patients treated with proton and carbon ion therapy at the Heidelberg ion therapy center using the raster scanning technique. Int J Radiat Oncol Biol Phys 81(5):e793–e801
