Cell Cannibalism in Oral Precancerous Lesions and Squamous Cell Carcinoma

Document Type : Original

Authors

1 Biomaterial Research Center, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran.

2 Oral and Dental Disease Research Center, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran.

3 Department of Oral & Maxillofacial Pathology, School of Dentistry, Iran University of Medical Sciences, Tehran, Iran.

4 Otolaryngology Research Center, Department of Otolaryngology, Shiraz University of Medical sciences, Shiraz, Iran.

Abstract

Introduction:
Cellular cannibalism is defined as a process of non-apoptotic cell death. This phenomenon has been indicated to be associated with aggressiveness, anaplasia, invasiveness, and metastatic potential of various malignancies. The Aim of this study is the evaluation of cell cannibalism in oral dysplastic lesions and oral cancer.
 
Materials and Methods:
A total of 31 cases of squamous cell carcinoma (SCC), 30 epithelial dysplasia, and 36 hyperkeratosis (HK) were enrolled in this Cross-sectional study. All hematoxylin and eosin tissue sections were examined in 10 high-power fields for tumor cell cannibalism. Data were analyzed using the Kruskal-Wallis and Fisher's exact test.
 
Results:
Cell cannibalism was found in all cases of SCC, 58.3% of dysplastic lesions, and 3.7% of HK cases. The mean number of cells with cannibalism was 19.48± 4.94 in SCC patients, 1.03± 1.25 in dysplastic lesions, and 0.03± 0.18in HK with a significant difference (P<0.001). High grades dysplastic and cancerous lesions exhibited more cannibalistic cells (P=0.01, P= 0.27, respectively).
 
Conclusions:
In addition to oral SCC, cell cannibalism was found in oral epithelial dysplasia; which was significantly more in SCC. This phenomenon was in association with grades of differentiation and might be considered a potential criterion for malignant transformation and high-grade lesions.

Keywords

Main Subjects


  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians. 2018;68(6):394-424.
  2. Chinn SB, Myers JN. Oral Cavity Carcinoma: Current Management, Controversies, and Future Directions. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2015;33(29):3269-76.
  3. Silverman S, Kerr AR, Epstein JB. Oral and Pharyngeal Cancer Control and Early Detection. Journal of Cancer Education. 2010;25(3):279-81.
  4. Warnakulasuriya S. Global epidemiology of oral and oropharyngeal cancer. Oral oncology. 2009 ;45 (4-5):309-16.
  5. Javadi S, Khademi B, Mohamadianpanah M, Shishegar M, Babaei A. Elective Submandibular Gland Resection in Patients with Squamous Cell Carcinomas of the Tongue. Iranian journal of otorhinolaryngology. 2021;33(114):23-9.
  6. Reibel J, Gale N, Hille J, Hunt J, Lingen M, Muller S, et al. Oral potentially malignant disorders and oral epithelial dysplasia. WHO classification of head and neck tumours. 2017;4:112-5.
  7. Tilakaratne WM, Jayasooriya PR, Jayasuriya NS, De Silva RK. Oral epithelial dysplasia: Causes, quantification, prognosis, and management challenges.Periodontology 2019;80(1):126-47.
  8. Ranganathan K, Kavitha L. Oral epithelial dysplasia: Classifications and clinical relevance in risk assessment of oral potentially malignant disorders. Journal of oral and maxillofacial pathology : JOMFP. 2019;23(1):19-27.
  9. Mehanna HM, Rattay T, Smith J, McConkey CC. Treatment and follow-up of oral dysplasia — A systematic review and meta-analysis. Head & Neck. 2009; 31(12):1600-9.
  10. Overholtzer M, Mailleux AA, Mouneimne G, Normand G, Schnitt SJ, King RW, et al. A nonapoptotic cell death process, entosis, that occurs by cell-in-cell invasion. Cell. 2007;131(5):966-79.
  11. Steinhaus J. Ueber Carcinom-Einschlüsse. Archiv für pathologische Anatomie und Physiologie und für klinische Medicin. 1891;126(3):533-41.
  12. Domingo-Claros A, Alonso E, Aventin A, Petit J, Crespo N, Ponce C, et al. Oligoblastic leukaemia with (8;21) translocation and haemophagocytic syndrome and granulocytic cannibalism. Leukemia research. 1996;20(6):517-21.
  13. Sharma N, Dey P. Cell cannibalism and cancer. Diagnostic cytopathology. 2011;39(3):229-33.
  14. Lugini L, Matarrese P, Tinari A, Lozupone F, Federici C, Iessi E, et al. Cannibalism of live lymphocytes by human metastatic but not primary melanoma cells. Cancer research. 2006;66(7):3629-38.
  15. Jain M. An overview on "cellular cannibalism" with special reference to oral squamous cell carcinoma.Experimental oncology.2015;37(4):242-5.
  16. Siddiqui S, Singh A, Faizi N, Khalid A. Cell cannibalism in oral cancer: A sign of aggressiveness, de-evolution, and retroversion of multicellularity. Journal of cancer research and therapeutics. 2019; 15(3):631-7.
  17. Jain M, Saawarn S, Gupta A, Ashok S, Mhaske S, Khan S, et al. Assessment of Tumor Cell Cannibalism as a Predictor of Oral Squamous Cell Carcinoma - A Histopathologic Correlation. The Gulf journal of oncology. 2017;1(23):52-6.
  18. Kinoshita M, Matsuda Y, Arai T, Soejima Y, Sawabe M, Honma N. Cytological diagnostic clues in poorly differentiated squamous cell carcinomas of the breast: Streaming arrangement, necrotic background, nucleolar enlargement and cannibalism of cancer cells. Cytopathology : official journal of the British Society for Clinical Cytology. 2018; 29(1):22-7.
  19. Jose D, Mane DR, Datar U, Muttagi S, Hallikerimath S, Kale AD. Evaluation of cannibalistic cells: a novel entity in prediction of aggressive nature of oral squamous cell carcinoma. Acta odontologica Scandinavica. 2014;72(6): 418-23.
  20. Sarode SC, Sarode GS. Neutrophil-tumor cell cannibalism in oral squamous cell carcinoma. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 2014;43(6):454-8.
  21. Sarode GS, Sarode SC, Karmarkar S. Complex cannibalism: an unusual finding in oral squamous cell carcinoma. Oral oncology. 2012;48(2):e4-6.
  22. Jose D, Mane DR, Datar U, Muttagi S, Hallikerimath S, Kale AD. Evaluation of cannibalistic cells: a novel entity in prediction of aggressive nature of oral squamous cell carcinoma. Acta odontologica 2014;72(6):418-23.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

  1. Fais S, Overholtzer M. Cell-in-cell phenomena in cancer. Nature reviews Cancer. 2018;18(12):758-66.
  2. Arya P, Khalbuss WE, Monaco SE, Pantanowitz L. Salivary duct carcinoma with striking neutrophil-tumor cell cannibalism. CytoJournal. 2011;8:15.
  3. Demir MA, Ryd W, Aldenborg F, Holmang S. Cytopathological expression of different types of urothelial carcinoma in situ in urinary bladder washings. BJU international. 2003;92(9):906-10.
  4. Kim Y, Choi JW, Lee JH, Kim YS. Spindle assembly checkpoint MAD2 and CDC20 overexpressions and cell-in-cell formation in gastric cancer and its precursor lesions. Human pathology. 2019; 85:174-83.
  5. Beham A, Regauer S, Friedrich G, Beham-Schmid C. Value of exfoliative cytology in differential diagnosis of epithelial hyperplastic lesions of the larynx. Acta oto-laryngologica Supplementum. 1997;527:92-4.
  6. Zargaran M. Cellular cannibalism and lichen planus malignancy: A suggestive hypothesis. Journal of investigative and clinical dentistry. 2018; 9(2):e12321-e.
  7. Sarode SC, Sarode GS, Chuodhari S, Patil S. Non-cannibalistic tumor cells of oral squamous cell carcinoma can express phagocytic markers. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 2017;46(5):327-31.
  8. Thakur M, Hazare V. Scanning electron microscopic study of surface epithelial cells in erosive and nonerosive oral lichen planus. J Contemp Dent Prac. 2011;12:463-8.