Journal List > J Korean Assoc Oral Maxillofac Surg > v.36(3) > 1032383

Kim, Kim, Han, Cha, Seo, Park, Yook, and Kim: Epithelial-mesenchymal transition in osteogenic sarcoma of the neck following oral squamous cell carcinoma


Postirradiation extraosseous osteogenic sarcomas are uncommon in the head and neck, despite the extensive use of high-dose radiation. It has been described as de novo radiation-induced neoplasm. We present a 73-year-old male who had been treated by radiotherapy for gingival cancer 7 years earlier and later developed extraosseous osteogenic sarcomas (EOSs) of the neck. Microscopically, the neck mass was composed with mesenchymal malignant cells with cartilaginous and osteogenic differentiation. Immunohistochemical stain demonstrated strong positivity of tumor cells for Snail, the one of major epithelial-mesenchymal transition (EMT) inducer. The E-cadherin expression was scarce, showing inverse relationship to Snail expression. Compared with previous squamous cell carcinoma (SCC) of the gingiva, the present EOS sample revealed the remained epithelial cells on cytokeratin immunohistochemistry, suggesting the tumor arise from the cells of epithelial origin. We have also reviewed the previous 6 cases of head and neck EOSs carefully. The clinicopathologic features of the unusual lesion suggest that it is an incomplete EMT of precedent epithelial malignancy rather than de novo pathology.


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Fig. 1.
A. Microscopically, primary gingiva lesion showed cords and nests of epithelial cells exhibiting aberrant accumulation of keratin.(arrow) B. Second primary tumor of buccal mucosa showed severe cellular abnormalities of hyperchromatism and pleomorphism. Scant production of keratin is notified. C-D. Microscopic feature revealed that lesion of the neck was composed of sarcomatous spindle cells with hypercellular cartilage and irregular osteoid.(D, aster-isk)(H&E staining, original magnification A, B, and D: x200, C: x100) (SCC: squamous cell carcinoma, EOS: extraosseous osteogenic sarcoma)
Fig. 2.
Axial CT scan reveals a neck mass (asterisk) of approximately 3.0×3.0 cm in left level III. (CT: computed tomography)
Fig. 3.
A. Immunohistochemical stain for previous SCC showed intense cytoplasmic staining for cytokeratin AE1/3, whole epithelial cell marker. B. Snail was detected in the nucleus of peripheral carcinoma cells. C. The cytoplasmic membranous expression of E-cadherin was occasional. D. The expression of N-cadherin could not be identified. E. The present EOS revealed the minimum positivity for cytokeratin Immunohistochemical staining. F. Sarcoma cells surrounding and whinin abnormal cartilage (asterisk) showed definitely strong Snail expression. G. E-cadherin disappeared through whole tumor samples. H. The scarce cytoplasmic membranous expression of N-cadherin was detected among the mesenchymal tumor cells. (Immunohistochemical stain, A and E: cytokeratin AE1/3, B and F: Snail, C and G: E-cadherin, D and H: N-cadherin, original magnification x200) (SCC: squamous cell carcinoma, EOS: extraosseous osteogenic sarcoma)
Table 1.
Clinicopathologic data of EOS in the head and neck
Case Author, year Gender, age Location History of RTx Treatment Recur/Mets Status Follow-up
1 Parsons, 1944 M, 53 Lip No Excision Local recur, Mandible mets1 Die 24 hrs after operation No
2 Juassawalla, 1964 M, 48 Submental No Excision Probable cerebral mets Dead 9 mos
3 Shanoff, 1967 M, 48 Chin Yes Excision Skull mets Dead 2 1/2 yr
4 Das Gupta, 1968 M, 41 Rt. Zygoma No Excision No Alive 12 1/2 y
5 Sordillo, ?2 No info Face No 2 2 2 2
6 Manning, 1986 M, 73 Rt. Parotid gland No Parotidectomy Unknown Alive 2
7 Present case M, 66 Neck Yes Excision No Alive 5 mos

1 The first lip lesion was SCC, but the recurred tongue was osteogenic sarcoma.(more than 3 years) The metastatic mandibular lesion (within months) was diagnosed radiologically, and necropsy was not permitted.

2 There is no related information. (SCC: Squamous cell carcinoma, EOS: extraosseous osteogenic sarcoma)

Table 2.
EOS associated with radiotherapy in the head and neck
Case Site and reason for RTx Previous treatment Amount of radiation Interval to development of EOS Site of EOS Remarks
3 Head and neck, chest and arm for multiple skin cancer (SCC) and precancer Excision, electrodesiccation, and irradiation unkown 14 yrs Chin History of benign lesion1
7 Gingiva and neck for SCC of gingiva Segmental mandibulectomy and cervical neck node dissection 9,900 cGy 7 yrs and 9 mos Neck Present case

1 The previous three biopsies showed myositis ossificans. (SCC: Squamous cell carcinoma, EOS: extraosseous osteogenic sarcoma)

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