Ghost cell odontogenic carcinoma: A rare case report and review of literature.

RATIONALE: Ghost cell odontogenic carcinoma is a rare malignant odontogenic carcinoma characterized by the presence of ghost cells. It has a nonspecific clinical and radiographic presentation and can be locally destructive and invasive, sometimes with distant metastases. However, no effective systemic therapy is currently recommended for such patients. PATIENT CONCERNS: The patient has been unable to undergo surgery or radiotherapy again. Therefore, he was referred to our department for a more aggressive, multimodal systematic treatment program. DIAGNOSES: The histopathological examination was morphologically suggestive of ghost cell odontogenic carcinomas. INTERVENTIONS: We report a case of locally invasive primary inoperable odontogenic shadow cell carcinoma in a 31-year-old Chinese man who achieved treatment with Toripalimab and chemotherapy, followed by Toripalimab maintenance therapy after 6 cycles. OUTCOMES: He achieved partial remission after treatment. The quality of life significantly improved after treatment. There were no grade 3/4 treatment-related adverse events during treatment. LESSONS: This case presented that Toripalimab and chemotherapy may be a safe and effective systemic therapy for ghost cell odontogenic carcinoma.

Molecular selection and functional divergence of HIF-α proteins in vertebrates.

HIF-α transcription factors, as key master regulators of oxygen homeostasis, constitute a subgroup of the large bHLH-PAS transcription factor family and have been identified in many vertebrates. Although the amino acid sequences of bHLH-PAS domain are conserved, the physiological and pathological roles of this family are variable. They also have different patterns of expression. It is possible that the HIF-α copies have been retained as a consequence of adaptive amino acid replacements or relaxed selective constraint which have conferred subtle changes in function after duplications. Phylogenetic analysis indicated that at least two major duplications had occurred early in the vertebrate lineages. Analyses of the ratios of nonsynonymous/synonymous substitution rates revealed that relaxation of selective constraints might play important roles over evolutionary time and shape variation in some members of the family. The coefficients of functional divergence (θ) estimated between pairwise comparisons of gene groups from HIF-1α, HIF-2α, and HIF-3α indicated statistically significant site-specific shift of evolutionary rates between them, suggesting that altered functional constraints may have taken place at some amino acid residues after their duplications. Moreover, we also mapped sites identified to have been relaxed from purifying selection onto the three-dimensional structure of human HIF-2α. Overall, our study demonstrated that the functional diversity of HIF-αs members may be caused by relaxed negative selection on the N-terminal transactivation domains after HIF-αs duplications, which recruited new partners leading to functional specificity.