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Sclerosing odontogenic carcinoma (SOC) is very rare. Moreover, it was only formally adopted in the 4th edition of the World Health Organization (WHO) classification of head and neck tumours in 2017.
SOC is a locally aggressive low grade malignancy primarily diagnosed based on its microscopic appearance (i.e., skeletal muscle invasion or perineural infiltration).
Therefore, this case provides undeniable evidence that SOC metastases are possible.
A 41-year-old woman presented with diffuse swelling of the left mandible. Clinical examinations showed a hard buccal expansion of the body of the mandible. Furthermore, axial post-contrast computed tomography (CT) revealed a heterogeneously enhanced space-occupying mass in the left mandible with the destruction of the buccal and lingual cortices (Fig. 1A). Thus, invasive growth into the masseter and mylohyoid muscles was highly suspected. Additionally, a neighbouring submandibular lymph node was enlarged (Fig. 1B), and a small superficial biopsy was interpreted as ‘features consistent with desmoplastic fibroma’. Therefore, a hemimandibulectomy with excision of an enlarged lymph node was performed. The surgical specimen was solid and hard, with an ill-defined tumour in the mandible measuring 6.0×4.5×3.3 cm (Fig. 1C).
Fig. 1(A) Axial and (B) coronal post-contrast computed tomography images showing enlargement of the submandibular lymph node (arrows) near the tumour (arrowheads) and submandibular gland (∗). (C) Gross appearance of the solid tumour. (D) Thin tumour cords compressed by sclerotic stroma. (E) Clear tumour cells. (F) Immunopositivity for cytokeratin (CK) 5/6. (G) Lymph node metastasis highlighted by CK5/6. Inset: tubular formation.
Histologically, the lesion was composed of scirrhous fibrous tissue in which small strands and islands of tumour cells were often difficult to discern. There were single-file thin cords of inactive looking odontogenic epithelium, and these cells were cuboidal or polygonal shaped with bland nuclear features (Fig. 1D). The mitotic figures were inconspicuous throughout the tumour. In the focal areas, scattered clear cells were observed (Fig. 1E), and they were unreactive with the periodic acid–Schiff staining.
Immunohistochemically, the tumour cells were highlighted by their diffuse and intense positivity for cytokeratin (CK) 5/6 (Fig. 1F), p40, p63, and CK19, but AE1/AE3 expression was variable. The average Ki-67 labelling index was approximately 15.9% in the highest part. Scattered epithelial clusters were observed in an extirpated lymph node; all were strongly positive for CK5/6 (Fig. 1G). Notably, several metastatic tumour nests formed the tubuloductal epithelial structures. Therefore, we diagnosed the patient with SOC with lymph node metastasis based on the overall findings.
One year after the mandibulectomy, reconstructive surgery was performed. Later, the patient was closely followed, and local recurrence was identified 3 years later. A CT examination revealed cortical expansion and destruction of the mandibular symphysis. Furthermore, a recurrent tumour occupied the left infratemporal fossa (Fig. 2A,B), which was confirmed by coronal post-contrast fat-suppressed T1-weighted imaging (Fig. 2C). The recurrent tumour was resected at another institution, and chemo-radiotherapy was administered because of positive margins. Currently, the patient is in clinical remission.
Fig. 2(A) Axial bone algorithm computed tomography (CT) image showing recurrence (arrows). (B) Axial non-contrast-enhanced soft tissue algorithm CT image showing infratemporal fossa involvement (∗). (C) Coronal post-contrast fat-suppressed T1-weighted image with abnormal enhancement in the orifice of the foramen ovale, suggesting perineural invasion (arrow). (D) Recurrent sclerosing odontogenic carcinoma with a densely collagenous stroma. (E) Reticular growth pattern. (F) Larger tumour nests. (G) Tumour cells encircling two peripheral nerves. (H) P63 expression.
In the recurrent tumour, the histopathology essentially matched that of the primary SOC (Fig. 2D). However, some compressed tumour cells exhibited a unique reticular growth pattern (Fig. 2E), and the solid SOC nests were slightly larger. They lacked overt squamous and ameloblastic differentiation (Fig. 2F). As expected, we observed considerable perineural infiltration (Fig. 2G). Unlike the primary lesion, spindle cell proliferation, necrotic tumour nests, and myxoid stroma, although focal, were evident. Immunohistochemical evaluation revealed an identical phenotype to the primary and metastatic SOCs (Fig. 2H). In additional sections, the tumour expanded extensively to involve surrounding tissue (Fig. 3A), and there were multiple infiltrating nests of clear cells in a very dense collagenous stroma (Fig. 3B). To verify the diagnosis, fluorescence in situ hybridisation (FISH) analysis was performed to investigate a rearrangement of the EWSR1 gene. There was no evidence of either a EWSR1 split or EWSR1-ATF1 gene fusion in any of the primary and recurrent tumours, consistent with the diagnosis of SOC.
Fig. 3The recurrent tumour. (A) Unquestionable infiltration into perineural (arrow) and perivascular (arrowhead) tissues. (B) Small clustered and single clear cells embedded in a hyalinised stroma.
Without cytological atypia, focal invasion into surrounding bone and muscle or intra- or peri-neural infiltration is the only criterion for diagnosing SOC as carcinoma.
Given the presence of clear tumour cells in our case, we performed a FISH molecular genetic study for EWSR1 arrangement characteristic of clear cell odontogenic carcinoma.
However, a nasopharyngeal squamous cell carcinoma case report described this unique growth pattern using the diagnostic terminology ‘reticular non-keratinising carcinoma’.
The SOC tumour in our case also expressed CK5/6, p40, and p63; thus, SOC may be a form of primary intraosseous non-keratinising squamous cell carcinoma.
An unusual maxillary tumor with tubuloductal epithelial structures, solid epithelial nests and stromal odontogenic ameloblast-associated protein deposits. Tubuloductal/syringoid variant of central odontogenic fibroma with amyloid?.
observed many duct-like epithelial structures in an amyloid variant of central odontogenic fibroma, suggesting ductal differentiation of neoplastic odontogenic epithelium. Evaluations of the lymph node metastasis in this study identified apparent tubular formation in the tumour nests, which has also been reported in at least three other cases.
A central maxillary tumor with bland cytology, partly sclerotic stroma, and neural involvement. Scleroing odontogenic carcinoma or epithelial neurotropism in an odontogenic fibroma?.
In summary, we report the first case of SOC with recurrence and metastasis. The latter finding emphasises that SOC can be truly malignant. Therefore, awareness of the metastatic potential of SOC is essential in clinical practice. Furthermore, pathologists should be aware that the microscopic features of SOC significantly vary in the literature, from central odontogenic fibroma to clear cell odontogenic carcinoma, ameloblastic carcinoma or primary intraosseous carcinoma, not otherwise specified.
Acknowledgements
We greatly thank Dr Rie Ohtomo and Dr Hirokazu Taniguchi of the Department of Clinical Laboratory, JR Tokyo General Hospital, for providing surgical specimens of a recurrent tumour; we would like to express our sincere gratitude to Dr Yukiko Sato and Dr Kengo Takeuchi of the Department of Pathology, Cancer Institute Hospital, for their significant contribution to molecular analyses. We also thank Editage (www.editage.com) for English language editing.
Conflicts of interest and sources of funding
This work was partially supported by research grants from the Sato Fund of the Nihon University School of Dentistry and by a grant from the Dental Research Center of the Nihon University School of Dentistry. The authors state that there are no conflicts of interest to disclosure.
References
Odell E.W.
Koutlas I.
Sclerosing odontogenic carcinoma.
in: El-Naggar A.K. Chan J.K.C. Grandis J.R. WHO Classification of Head and Neck Tumours. 4th ed. IARC,
Lyon2017: 209-210
An unusual maxillary tumor with tubuloductal epithelial structures, solid epithelial nests and stromal odontogenic ameloblast-associated protein deposits. Tubuloductal/syringoid variant of central odontogenic fibroma with amyloid?.
A central maxillary tumor with bland cytology, partly sclerotic stroma, and neural involvement. Scleroing odontogenic carcinoma or epithelial neurotropism in an odontogenic fibroma?.
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