Extraskeletal Myxoid Chondrosarcoma of Floor of Mouth—A Rare Case Report and Review of Literature

Abstract

Introduction

Chondrosarcomas are rare malignancies of the cartilage and myxoid chondrosarcoma is its variant which commonly occurs in soft tissue of extremities. Extraskeletal chondrosarcoma is a rare malignant neoplasm of bone or soft tissue origin and is characterized by the presence of spindle cells admixed with well differentiated cartilage or chondroid stroma. They are mostly radioresistant tumours and surgical resections with adequate margins is considered as the ideal treatment modality with adjuvant radiotherapy in high grade tumours and add on chemotherapy, in case of presence of poor prognostic factors.

Case Report

A 51-year-old diabetic, hypertensive female patient presented to our outpatient department with difficulty in chewing food for a duration of 6 months. On clinical examination, she had an ulceroproliferative growth involving right lower alveolus and floor of mouth. MRI face and neck with contrast showed a 4.1 × 2.9 × 4.5 cm lesion involving right lower alveolus extending to floor of mouth. Biopsy showed features of extraskeletal myxoid chondrosarcoma. She was planned for upfront surgery (Right composite resection with modified radical neck dissection with free fibula flap). Patient was stable post-surgery and was discharged in stable condition. Final histopathology report was high grade myxoid chondrosarcoma. The case was presented in tumour board and the patient was planned for adjuvant radiotherapy. She has been on regular follow up for the past 2 years and shows no signs of recurrence.

Conclusion

Extraskeletal myxoid chondrosarcoma of oral cavity is a rare entity and very few cases are reported. It is a malignant neoplasm which is diagnosed with the help of immunohistochemistry. Surgery is the ideal modality of treatment accompanied by adjuvant radiotherapy in cases of high-grade tumours.

Introduction

Chondrosarcomas are malignant mesenchymal tumours, commonly seen in long bones and pelvis. It is a rare neoplasm to be found in head and neck region. Majority of chondrosarcomas are diagnosed between 5th to 7th decades [1].

Chordomas of soft parts and non-synovial chondrosarcomas are categorised under extraskeletal cartilaginous tumours. Myxoid and mesenchymal variants of chondrosarcomas are classified under non synovial soft tissue chondrosarcomas [2].

Extraskeletal chondrosarcoma is a malignant tumour with cells that produce cartilage matrix and are commonly seen in peripheral long and flat bones [3]. Stout and Verner first described this entity in 1953 [4] and was classified as a separate clinicopathological entity by Enziger and Shiraki in 1972 [5]. It accounts for 10 to 20% of malignant bone tumours [6] and 2% of soft tissue sarcomas [7]. In 2005 it was classified as soft tissue tumour with uncertain differentiation by the WHO Classification of Soft Tissue Tumours [8].

Myxoid chondrosarcomas are commonly seen involving the limbs and rarely seen in head and neck regions. This histological variant is characterized by abundant chondroid matrix and malignant chondroblastic cells arranged in cords resembling chordoma [9]. Microscopically tumour cells of extraskeletal myxoid chondrosarcoma appear as eosinophilic granular with vacuolated cytoplasm and round to oval nuclei. IHC is positive for vimentin with variable staining for S100 and neuroendocrine markers [10].

Surgical treatment is considered gold standard as these tumours are less sensitive to chemotherapy and radiotherapy. Local and distant metastasis is common especially in high grade aggressive tumours [11].

We report a case of extraskeletal myxoid chondrosarcoma of the oral cavity in a 51-year-old woman.

Case Report

51-year-old diabetic, hypertensive female presented to the outpatient department with complains of difficulty in chewing food for a duration of 6 months. On examination, an ulceroproliferative lesion measuring about 4 × 3 cm was noted over the right lower alveolus extending to the floor of mouth (Fig. 1a).

Fig. 1.

a. Clinical picture of Lobulated lesion involving right side floor of mouth and lower alveolus. b. Incision used for composite resection and neck dissection. c. Intraoperative picture of partially resected lesion. d,e. Specimen photographs after complete resection

MRI face and neck with contrast showed T2 heterogenous 4.1 × 2.9 × 4.1 cm hyperintense lobulated lesion along lingual aspect of right mandible. It was seen infiltrating mandibular alveolus in molar region with cortical thinning and erosions of lingual aspect of mandible. Medially indenting oral tongue with displacement of sublingual gland, hyoglossus and mylohyoid muscle, posteriorly reaching till retromolar trigone. No significant lymphadenopathy was noted. (Fig. 2a-d) PET Scan findings were congruent with MRI findings. PET scan showed an FDG avid lesion measuring 4.5 × 3.8 × 1.5 cm involving floor of mouth and lower alveolus till retromolar trigone. No significant lymphadenopathy noted (Fig. 3a-d). Biopsy showed features of myxoid chondrosarcoma.

Fig. 2.

MRI plain and contrast photographs showing T2 heterogenous 4.1 × 2.9 × 4.1 cm hyperintense lobulated lesion along lingual aspect of right mandible. It was seen infiltrating mandibular alveolus in molar region with cortical thinning and erosions of lingual aspect of mandible. Medially indenting oral tongue with displacement of sublingual gland, hyoglossus and mylohyoid muscle. Posteriorly reaching till retromolar trigone. No significant lymphadenopathy was noted. Green arrow indicating the disease. a. Axial, b. coronal c. sagittal d. axial

Fig. 3.

- PET scan showed an FDG avid lesion measuring 4.5 × 3.8 × 1.5 cm involving floor of moth and lower alveolus till retromolar trigone. Green arrow pointing to disease. a,b. Axial, c,d. Coronal

Patient was planned for upfront surgery. She underwent right composite resection (segmental mandibulectomy with wide local excision of floor of mouth) (Fig. 1b-c) with right modified radical neck dissection type III and reconstruction was done with free fibula flap.

Specimen was sent for histopathological examination (Fig. 1d-e). The final histopathology report was of extraskeletal myxoid chondrosarcoma measuring 4 × 3 × 1.8 cm. All margins were free of tumour. Microscopic examination of tumour showed presence of multinodular tumour with cellular spindle cell proliferation in an abundant myxoid background. Spindle cells showed variable nuclear morphology with nuclear atypia, pleomorphism with a few bizarre nuclei and frequent mitotic figures with focal areas of necrosis. Focal areas show vascular proliferation within tumour cells. In addition, areas of cartilaginous differentiation also noted. Superficial cortical erosion of mandible was also noted. On IHC, tumour cells were positive for S100 (heterogenous), INSM1, CDK4 and SATB2 and negative for CK, P40, DESMIN, SMA, MYOD1, CD117, CD34, STAT6 and Synaptophysin (Fig. 4a-f). 15 lymph nodes were harvested with no signs of malignancy.

Fig. 4.

(a) Unremarkable squamous mucosa with underlying stroma infiltrated by diffuse proliferation of neoplastic spindle to epithelioid cells in a chondromyxoid background H and E 100x. (b) The neoplastic cells exhibit moderate atypia with significant mitosis (arrow). The background is chondromyxoid. H and E 200 x. (c) CK highlights squamous mucosa while tumor cells are immunonegative. DAB 50x. (d) Tumor cells show heterogenous positive immunoexpression for S100. DAB 200x. (e) Tumor cells are positive for INSM1 with nuclear staining. DAB 100x. (f) Tumor cells show positive immunoexpression for SATB2. DAB 100x

Post operatively, patient was stable and discharged on post operative day 5. She was initially kept on ryles tube feeding for a period of 18 days post surgery, following this oral feeding was initiated and patient faired well. The case was presented in tumour board and decision was taken to give adjuvant radiotherapy to the patient. She completed 30 fractions of radiotherapy and has been on regular follow up for the past 2 years with no signs or symptoms of residual or recurrent disease on clinical and radiological examination.

Discussion

Extraskeletal myxoid chondrosarcoma is a high-grade malignancy. It accounts for 2.5% of all soft tissue sarcomas. It shows a slight male predominance with peak incidence in the 50–60-year age group. Only 5 to 10% cases occur in the head and neck region, mostly involving maxilla, nasal cavity and sphenoid [12]. Only 7 cases of extraskeletal myxoid chondrosarcoma of oral cavity have been recorded prior to our case (Table 1). All the previously reported cases underwent surgical treatment. 2 of the cases received adjuvant radiotherapy and 1 patient received adjuvant chemoradiotherapy.

Table 1.

Extraskeletal chondrosarcoma of oral cavity—review of reported cases

SL No:	Age/sex	Clinical features	Diagnosis	Site	Surgical treatment	Adjuvant	Follow up	Article
1.	105/F	Swelling over maxillary area	Extraskeletal chondrosarcoma (treatment naïve)	Maxilla	Surgery	No	1 year—disease free	Francesca et al. [12]
2.	28/M	Pain and swelling over jaw.	Extraskeletal myxoid chondrosarcoma (recurrence)	Mandible	Surgery	CTRT	3 year—disease free	Prabha Verma et al. [15]
3.	22/M	Swelling over gingiva	Extraskeletal myxoid chondrosarcoma	Mandible	Surgery	No	9 months—disease free	Chen et al. [24]
4.	51/M	Swelling over mentum	Extraskeletal myxoid chondrosarcoma	Mentum	Surgery	No	15 months—disease free	Shindo et al.  [25]
5.	61/M	Swelling over cheek	Extraskeletal myxoid chondrosarcoma	Maxilla	Debulking Surgery	RT	1 year—Lung metastasis, brain metastasis(metastectomy) and liver metastasis(Palliative chemotherapy)—death due to disease	Ganguly et al. [2]
6.	13/M	Swelling over cheek	Extraskeletal myxoid chondrosarcoma	Masticator space	Surgery	RT	1 year—death due to locoregional recurrence	Romanach et al. [26]
7.	45/M	Numbness over maxillary area	Extraskeletal myxoid chondrosarcoma	Maxilla	Surgery	No	18 months—disease free	Jawad et al. [27]
8.	51/M	Lesion over floor of mouth	Extraskeletal myxoid chondrosarcoma	Floor of mouth	Surgery	RT	24 months—disease free	Dabas et al. ( current paper)

Myxoid chondrosarcoma is a rare histological variant which is rarely seen in head and neck region [13]. These patients have a characteristic t (9,22) (q22, q12.2) translocation with higher rate of local recurrence and high rate of late death [14]. The other common translocation associated with this disease is t (9;17) (q22; q11.2) [15]. The most frequent sites of metastasis include lymph nodes and lungs. Myxoid chondrosarcomas have high incidence of pulmonary metastasis irrespective of the histologic grade [13].

Radiologically myxoid chondrosarcoma is characterized by permeative pattern of osseous destruction and associated soft tissue mass. CT scan shows matrix mineralisation and myxoid stroma shows exceptionally high-water content with low attenuation by CT and very high signal intensity by T2-weighted MR [16]. Quantitative DWI may be useful for differentiating chondrosarcoma from other poorly contrast-enhanced lesions [17]. They usually appear as single or multiple radiolucencies with ill-defined irregular borders with sun burst or ground glass appearance. FDG PET and MRI scans are done for initial staging of these tumours [18]. Histopathological examination and IHC are needed to make a confirmatory diagnosis.

Wide local excision for chondrosarcomas is ideal to control local recurrence irrespective of the previous excision or recurrence status. Adjuvant radiotherapy is reserved for high-grade, margin-positive, or recurrent lesions. Gao Z et al., suggested that adjuvant RT combined with surgery can improve both overall survival and cancer-specific survival of patients with myxoid chondrosarcomas [19]. Ifosfamide and Adriamycin based chemotherapy can be considered for recurrent, high-grade lesions with a high proliferative index to decrease loco-regional and distant recurrence, although there is no level 1 evidence available for the same [20].

The histological differential diagnosis for extraskeletal chondrosarcoma includes chondrosarcoma with fibrosarcomatous metaplasia, osteosarcoma, chordoma, chondroblastoma, synovial sarcoma, myxoid liposarcoma and Ewing’s sarcoma [21]. Any cartilaginous tumour which rapidly increases in size and is associated with pain should draw a high index of suspicion for malignancy [22].

Low grade chondrosarcoma has good prognosis and is characterized by abundant chondroid matrix with poor cellularity. High grade tumours are characterized with myxoid matrix and high cellularity which easily metastasize and have a bad prognosis [23]. It has skeletal and extraskeletal variants. The skeletal variant, as the name suggests typically arises from bones and extraskeletal variant arises most commonly from soft tissues with high rates (~ 40%) of local recurrence, metastasis, and mortality [14].

Conclusion

Very little literature has been published on extraskeletal chondrosarcoma of head and neck region. Extraskeletal chondrosarcoma is generally a low-grade tumour, but it can have an aggressive course on the basis of location, size of tumour and adverse histological features like high cellularity and anaplasia. Surgery is considered the gold standard of treatment in resectable cases. Adjuvant can be considered in high grade and aggressive tumours. Poor prognostic factors include large tumour size, early recurrence, high grade, high Ki 67 index and the presence of lymphovascular invasion.

Funding

None.

Data Availability (data transparency)

All material submitted in the article are original.

Declarations

Conflict of Interest

No potential conflict of interest relevant to this article exist.

Compliance with ethical standards

Written and informed consent has been taken from the patient for the procedure and all procedures have been done ethically.