Mesenchymal chondrosarcoma of maxilla in paediatric patient

Abstract

Chondrosarcoma (CS) is a malignant tumour of long and flat bone characterised by the formation of cartilage. Mesenchymal chondrosarcoma (MCS) is a rare subtype of CS that is more aggressive and may lead to erroneous diagnosis in a limited biopsy. The diagnosis is mainly based on the histopathological appearance of biphasic pattern of undifferentiated small round cells separated by islands of well-differentiated hyaline cartilage. We report a case of 13-year-old boy who initially presented with gum swelling and the biopsy result suggested a benign fibrous lesion. Following an extensive lesion shown in radiologic findings, the tumour excision was done and finally was diagnosed as an MCS of the maxilla. The patient was given postoperative chemotherapy (EURO-EWING 99 regimen), and now on regular follow-up for monitoring of local recurrence or tumour metastasis.

Background

Chondrosarcoma (CS) is a malignant tumour composed of cartilage-producing cells, mostly found in flat and peripheral long bones.^{1 2} They are rarely found in the head and neck region which account for 0.1% of head and neck neoplasia.³ There are many histological variants of CS being reported which include clear cell, dedifferentiated, myxoid and mesenchymal subtypes.^3–5 Mesenchymal chondrosarcoma (MCS) is a rare histological variant that accounts 2%–10% of all CS^{4 6} and has a high propensity for head and neck region.⁷ Unlike conventional CS which is more frequently seen in old age groups, MCS is mostly seen in young adults.⁷

In children and adolescents, MCS accounts for up to 25% of all CS.^{8 9} This rare tumour has been well known for its aggressive nature with an inclination for late recurrence and metastasis.^{3 6} The peak age incidence is in the second or third decades of life and the most common locations are craniofacial and lower extremity bones, followed by ribs and chest wall.¹⁰ The maxilla and mandible are among the common sites of involvement of MCS, followed by the vertebrae, the ribs, the pelvis and the humerus.¹¹ The tumours show a less aggressive course when found in the long bones as compared with the head and neck bones, which the latter had a greater rate of growth, recurrence and metastasis. Therefore, morphological distinction of this variant is important to ensure the complete removal and a proper management. The aim of this report is to present a rare case of MCS of maxilla and review the literature on the morphological identification, clinical course and prognosis.

Case presentation

A 13-year-old boy visited a dental clinic due to a 2-day history of a toothache associated with gum swelling over the right upper molar region. He was treated with a course of antibiotic. However, the swelling progressively increased in size and eventually caused dysphagia and trismus. He also had a bilateral persistent nasal blockage with recurrent episodes of minimal epistaxis.

On examination, the child was pale but not in respiratory distress, and his hydration status was normal. There was asymmetry of the face with prominent bulging over the right maxillary region with normal overlying skin appearance (figure 1B). Anterior nasoendoscopic examination showed both nostrils were fully obstructed with soft tissue mass, but no contact bleeding from the mass. Intraorally, a bluish lobulated smooth mass was seen extruding from the right upper alveolar region (figure 1A). The mass was about 3x4 cm in size, and it prevented the patient to fully close his mouth. Otherwise, the tongue was mobile and not swollen. No palpable cervical lymphadenopathy noted.

Figure 1.

Clinical presentation of the patient. (A) A lobulated bluish mass was seen extruding from the right upper alveolar region. (B) Afacial asymmetry of the right maxillary region. The patient also had difficulty in closing the mouth due to the protruding mass from the oral cavity.

Investigations

A small tissue biopsy was taken from the oral mass under local anaesthesia. The histopathological examination from the biopsy reported a vascularised fibrocollagenous tissue, with juvenile nasal angiofibroma as one of the possible differential diagnosis.

CT from head to upper thorax revealed a heterogeneously enhancing soft tissue mass occupying the right maxillary sinus with ring calcification and hypodensities within (figure 2A,B). The mass extended laterally to occupy infratemporal fossa and buccal space, medially into nasal cavity with the erosion of maxillary wall and widening of osteomeatal complex. Superiorly, thinning of the right inferior orbital wall was seen and inferiorly, erosion of inferior wall of maxillary sinus was noted with the extension of the lesion into the oropharynx. Anteriorly, there was thinning and erosion of the anterior right maxillary wall. Obliteration of the bilateral fossa of Rosenmuller and torus tubarius were also seen (figure 2A). CT angiogram further confirmed the arterial supply of a tumour which arises from the maxillary branch of the right external carotid artery.

Figure 2.

CT imaging of paranasal sinuses. (A) Axial view. (B) Coronal view showing a heterogeneously enhancing soft tissue mass occupying the right maxillary sinus with thin ring calcifications and hypodensities within. The mass is extending laterally to occupy infratemporal fossa and buccal space, and medially into nasal cavity with the erosion of maxillary wall and widening of ostiomeatal complex.

Histopathological examination revealed a biphasic pattern of a tumour characterised by multiple islands of well-differentiated hyaline cartilage (figure 3A) that blend gradually with primitive or undifferentiated small round blue cells (figure 3B). The transition of the two patterns was abrupt in some regions and gradual in most other areas. The hyaline cartilage component was benign appearing, resemble mature cartilage with minimal atypia (figure 3C). The small cells exhibited oval to spindle hyperchromatic nuclei with myopericytomatous pattern and scattered abnormal mitotic figures (figure 3D). Immunohistochemically, the small cells of the cartilaginous component demonstrated positive immunostaining for vimentin and CD99, but negative for S100 protein, CD34 and CD117. The histological features are consistent with MCS.

Figure 3.

Histopathological examination of mesenchymal chondrosarcoma. (A) Multiple islands of well-differentiated hyaline cartilage (H&E stain, x100). (B) The hyaline cartilage blend gradually with primitive or undifferentiated small round blue cells at the periphery, showing abrupt transition only in some foci (H&E stain, x200). (C) The hyaline cartilage component is benign appearing, resemble mature cartilage with minimal atypia, whereas the small blue cells exhibit oval to spindle hyperchromatic nuclei with some degree of pleomorphism (H&E stain, x400). (D) Areas of hypercellular hyperchromatic spindle cells display myopericytomatous pattern with scattered abnormal mitosis (H&E stain, x400).

Differential diagnosis

The patient had been diagnosed as benign lesion that suggestive of juvenile nasal angiofibroma from the first biopsy because the microscopic findings only revealed a vascularised fibrocollagenous tissue with areas of scattered pleomorphic spindle cells. No chondroid matrix found. Further microscopic sections from the subsequent biopsy showed predominantly a mature-looking cartilagenous island within a myxoid stroma mixed with mesenchymal spindle cells. Lacking of malignant features in this tissue sample gave an impression of chondromesenchymal hamartoma. However, the third sample received from a deeper tumour extension revealed a highly cellular mesenchymal tumour of poorly differentiated spindle cells with some degree of pleomorphism and abnormal mitosis. Combining the histomorphological features of all biopsies and excised tissue, supported by extensive tumour growth on radiological findings gave a final diagnosis of MCS.

Treatment

A combined endoscopic and open excision of a tumour was done by otorhinolaryngology and oromaxillofacial team. Intraoperatively, there was a large encapsulated tumour occupying the whole right maxillary sinus, right nasal cavity and nasopharynx. The tumour also extends into the left posterior choana and right infratemporal fossa. The tumour had eroded through the right maxillary tuberosity and alveolus into the oral cavity. The tumour was successfully removed en bloc. A temporary surgical plate was anchored with the right transzygomatic wiring to cover the postexcision defect in hard palate.

The patient presented with epistaxis a month postoperative. The endoscopic examination and repeated CT scan of head and neck revealed residual tumours within the right maxillary sinus, extending into the right sphenopalatine foramen, pterygopalatine fossa, pterygomaxillary fissure and infratemporal fossa. He underwent a second operation 6 weeks after the previous surgery where the excision of the tumour was done via Caldwell-luc approach. The orbital floor was reconstructed by fixing the orbital floor mesh with two screws via the right blepharoplasty approach.

The patient was referred to paediatric oncologist for further management. He was given chemotherapy of EURO-EWING 99 regimen protocol that is composed of vincristine, ifosfamide, doxorubicin and etoposide. He had uneventfully undergone five cycles of chemotherapy up to date. The patient will be subjected to local radiotherapy after completing the six cycles of chemotherapy.

Outcome and follow-up

Follow-up visits every 1–2 monthly revealed no new lesion. Patient was well and responded to chemotherapy.

Discussion

A review on literatures shows that CS of the maxillofacial region is extremely rare. MCS is a rare type of CS which was described as a biphasic tumour comprising of spindle cell mesenchyme interspread with areas of chondroid differentiation.^{3 5–12} The jaw bones are among the favourite site for MCS.^7–13 This tumour is malignant in nature and is histogenetically originated from mature cartilaginous tissue.¹⁴ Despite the maxillary bone is predominantly membranous ossification, MCS has been best ascribed to the vestigial nests of cartilage that originated either from cartilage tissue in incisive papilla, or foci cartilaginous nasal capsule or could be from paraseptal cartilage.¹⁵

MCS of head and neck area is mostly found in the maxilla with the most common site is at the anterior alveolus where the existing nasal cartilage is present.^{16 17} In our case, the mass initially arises from the right maxilla as a protruding mass from the right upper alveolar region. The early sign of the right upper gum discomfort had misled the medical practitioner on making a diagnosis of a tooth infection. Based on a study of 36 MCS of maxilla conducted by Tien et al, the most common clinical presentation was a mass or growth in 68% of cases, followed by nasal obstruction (32%), epistaxis (32%) and tooth mobility (24%).¹² Our reported case complaint of a protruding mass in the right upper alveolar region and followed with bilateral nasal obstruction and recurrent epistaxis. The later symptoms were due to tumour eroding the surrounding bone and mucosa. This study revealed the period of signs and symptoms before diagnosis ranged from 2 weeks to 4 years.⁷ Our patient was diagnosed of MCS after a period of 8 weeks from the first symptoms' presentation.

There is no classical radiographic features of MCS. Radiographically, these lesions appear as osteolytic, radiolucent shadows with ill-defined or ragged borders. The radiolucent part mostly contains scattered foci, which are formed by ossification of the cartilage matrix. It usually presents with profound infiltration within the osseous trabeculae without significant resorption.¹⁷ Our case presented with a heterogeneously enhancing soft tissue mass, occupying the right maxillary sinus with thin ring calcifications and hypodensities within. The mass erodes the anterior, inferior and medial maxillary walls.

Diagnosis can only be established by histopathological examination. Microscopically, the tumour shows a proliferation of hyaline cartilage formed by a sarcomatous stroma containing stellate, spindle-shaped and round cells. The cells have a greater degree of pleomorphism and atypia.¹⁸ The cartilaginous element in MCS is relatively well differentiated and may resemble mature hyaline cartilage.¹⁹ The transition between the two patterns may be quite abrupt and may lead to erroneous diagnosis if only a limited region is sampled. Immunohistochemical staining is indistinctive. The small round cells stain positive for CD99, vimentin and leu7. However, no characteristic molecular marker reliably differentiates it from other round blue cell tumours. Therefore, the pathological identification primarily relies on the morphological characteristic of the biphasic pattern.

The differential diagnoses include small round blue cell neoplasms such as Ewing sarcoma or primitive neuroectodermal tumours (PNETs), dedifferentiated CS, small cell osteosarcoma and monophasic synovial sarcoma.^{6 19 20} The identification of chondroid matrix and undifferentiated mesenchymal cells is crucial for an accurate diagnosis. The cells in Ewing sarcoma contain cytoplasmic glycogen but lack cartilaginous component, and haemangiopericytoma-like pattern of MCS.^{6 20} PNET contains more pleomorphic small cells than in MCS with the presence of rosettes. Dedifferentiated CS shows large and markedly pleomorphic spindle cells with atypical nuclei, whereas MCS shows uniform nuclei of small cells. There is a sharp margin between both components of spindle and cartilaginous cells in dedifferentiated CS but in MCS, both are blended gradually. Small cell osteosarcoma can be differentiated from MCS by the presence of osteoid in lace-like pattern Monophasic synovial sarcoma of poorly differentiated type can be separated from MCS by the absence of hyaline cartilage. Absences of keratins, especially CK7, and epithelial membrane antigen (EMA) can also differentiate MCS from synovial sarcoma.²¹

Management of MCS is less explored because of the rare and variable nature of the disease, but treatment patterns have evolved and are identified throughout the literature. Surgery is the mainstay of local treatment with studies showing better survival in patients who underwent wide surgical resection.⁶ In view of the overall lesser incidence of metastasis, neck dissection is not mandatory.¹⁷ The effectiveness of adjuvant chemotherapy and/or radiotherapy in addition to surgical resection is not well defined.²² Chemotherapy should be considered as adjuvant therapy in those cases with aggressive behaviour and having a propensity for metastasis, rapid local recurrence and high-grade lesions.^{5 17} This patient was treated surgically via combined endoscopic and open approach tumour resection. Considering the aggressive nature of MCS, the paediatric oncology team had decided for chemotherapy (EURO-EWING 99 regimen) and will be subjected to local radiotherapy postoperatively.

The prognosis appears to be related to the location of a tumour, the adequacy of the primary surgical resection and the histological grade of the neoplasm. Generally, the prognosis is poor because of the tumour’s tendency for local recurrences and metastasis. Recurrence is frequent because of the complicated location that does not allow complete surgical excision of the lesion. The longest disease-free interval recorded was of around 20 years. The primary areas for metastasis are the lungs and bone. The reported 5-year and the 10-year survival rate is 48% and 28%, respectively.⁵ In our case, the patient does not have any evidence of lung metastasis at the time of diagnosis. A close and long-term follow-up is mandatory knowing the high percentage of metastasis and its local recurrence potential.

Learning points.

• Mesenchymal chondrosarcoma (MCS) is a rare subtype of chondrosarcoma that is more aggressive and pose a diagnostic dilemma especially in a limited tissue biopsy

• The diagnosis of MCS depends on the presence of biphasic pattern of a tumour, characterised by multiple islands of well-differentiated hyaline cartilage that blend gradually with primitive small round blue cells. Therefore, the identification of chondroid matrix and undifferentiated mesenchymal cells is crucial for an accurate diagnosis.

• The best treatment for MCS is surgical resection with wider margins. Chemotherapy and radiotherapy are optional but worth added in aggressive lesion.

• Effective teamwork and communication between multidisciplinary team members, including pathologists, radiologists, head and neck surgeons, oromaxillofacial surgeons, paediatrician and oncologists, are essential in order to achieve an accurate diagnosis and timely patient care.