Merkel cell cancer pathophysiology

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Overview

Merkel cell carcinoma (MCC) is an unusual cutaneous malignancy of neuroendocrine origin.Merkel nerve endings are mechanoreceptors in the skin.Merkel cells are normal components in the basal layer of the epidermis of the skin.

Pathophysiology

Physiology

The normal physiology of merkel cells can be understood as follows:[1]

Pathogenesis

Merkel cell polyomavirus

UV radiation

Immunosuppression

  • Patients who underwent organ transplant are also very also prone to developing merkel cell carcinoma due to immunosuppression.
  • Patients who are suffering with HIV and malignancies especially B cell origin are also likely prone to develop merkel cell carcinoma due to immunosuppression.
  • The exact pathogenesis of how immunosuppression leads to merkel cell carcinoma is not completely understood.

Genetics

Genes involved in the pathogenesis of merkel cell carcinoma include:

  • TP53 gene mutations
  • Retinoblastoma (RB1) gene mutations
  • NOTCH1
  • PRUNE2
  • HRAS
  • PIK3CA
  • KNSTRN
  • PREX2, and
  • RAC1

Gross Pathology

On gross pathology of merkel cell carcinoma

Merkel cell carcinoma gross pathology
https://commons.wikimedia.org/wiki/File:Merkel_Cell_Carcinoma_buttock_45-year-old_woman.jpg#/media/File:Merkel_Cell_Carcinoma_buttock_45-year-old_woman.jpg

Microscopic Pathology

On microscopic histopathological analysis, trabecular pattern, monotonous round tumor cells, mitotic figures, atypical fibroxanthoma-like areas and dusty chromatin are characteristic findings of merkel cell carcinoma.

Merkel cell carcinoma
https://commons.wikimedia.org/wiki/File:Merkel_cell_carcinoma_-_very_high_mag.jpg#/media/File:Merkel_cell_carcinoma_-_very_high_mag.jpg

References

  1. Halata, Zdenek; Grim, Milos; Bauman, Klaus I. (2003). "Friedrich Sigmund Merkel and his ?Merkel cell?, morphology, development, and physiology: Review and new results". The Anatomical Record. 271A (1): 225–239. doi:10.1002/ar.a.10029. ISSN 0003-276X.
  2. Feng H, Shuda M, Chang Y, Moore PS (February 2008). "Clonal integration of a polyomavirus in human Merkel cell carcinoma". Science. 319 (5866): 1096–100. doi:10.1126/science.1152586. PMC 2740911. PMID 18202256.
  3. Sharp CP, Norja P, Anthony I, Bell JE, Simmonds P (February 2009). "Reactivation and mutation of newly discovered WU, KI, and Merkel cell carcinoma polyomaviruses in immunosuppressed individuals". J. Infect. Dis. 199 (3): 398–404. doi:10.1086/596062. PMID 19090778.
  4. Carter JJ, Paulson KG, Wipf GC, Miranda D, Madeleine MM, Johnson LG, Lemos BD, Lee S, Warcola AH, Iyer JG, Nghiem P, Galloway DA (November 2009). "Association of Merkel cell polyomavirus-specific antibodies with Merkel cell carcinoma". J. Natl. Cancer Inst. 101 (21): 1510–22. doi:10.1093/jnci/djp332. PMC 2773184. PMID 19776382.
  5. Kassem A, Schöpflin A, Diaz C, Weyers W, Stickeler E, Werner M, Zur Hausen A (July 2008). "Frequent detection of Merkel cell polyomavirus in human Merkel cell carcinomas and identification of a unique deletion in the VP1 gene". Cancer Res. 68 (13): 5009–13. doi:10.1158/0008-5472.CAN-08-0949. PMID 18593898.
  6. Schowalter RM, Pastrana DV, Pumphrey KA, Moyer AL, Buck CB (June 2010). "Merkel cell polyomavirus and two previously unknown polyomaviruses are chronically shed from human skin". Cell Host Microbe. 7 (6): 509–15. doi:10.1016/j.chom.2010.05.006. PMC 2919322. PMID 20542254.
  7. Heath M, Jaimes N, Lemos B, Mostaghimi A, Wang LC, Peñas PF, Nghiem P (March 2008). "Clinical characteristics of Merkel cell carcinoma at diagnosis in 195 patients: the AEIOU features". J. Am. Acad. Dermatol. 58 (3): 375–81. doi:10.1016/j.jaad.2007.11.020. PMC 2335370. PMID 18280333.
  8. Miller RW, Rabkin CS (February 1999). "Merkel cell carcinoma and melanoma: etiological similarities and differences". Cancer Epidemiol. Biomarkers Prev. 8 (2): 153–8. PMID 10067813.
  9. Agelli M, Clegg LX (November 2003). "Epidemiology of primary Merkel cell carcinoma in the United States". J. Am. Acad. Dermatol. 49 (5): 832–41. doi:10.1067/S0190. PMID 14576661.
  10. Girschik J, Thorn K, Beer TW, Heenan PJ, Fritschi L (November 2011). "Merkel cell carcinoma in Western Australia: a population-based study of incidence and survival". Br. J. Dermatol. 165 (5): 1051–7. doi:10.1111/j.1365-2133.2011.10493.x. PMID 21711338.