Basal cell carcinoma pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Maneesha Nandimandalam, M.B.B.S.[2]

Overview

Basal cell carcinoma is one of the most common skin cancers. It is commonly known as rodent ulcer due to its distinct morphology characterized by pearly pink nodules with telangiectasias, rolled borders, and central crusting with or without an ulcerating lesion. The majority common cause for the development of the basal cell carcinoma involves radiation exposure and mutations that involve many genes including sonic hedgehog gene, PTCH1 gene, and other gain-of-function mutations which further depend on the subtypes such as nodular, superficial, Infundibulocystic, fibroepithelial, morpheaform, infiltrative, micronodular, and basosquamous basal cell carcinomas.

Pathophysiology

Genetics

The development of basal cell carcinoma is the result of multiple genetic mutations such as sonic hedgehog pathway mutations, and PTCH1 gene mutations

 
 
 
Loss of PTCH1
 
 
 
Gain of function SMO
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lack of SMO inhibition
 
 
 
Activation of
SMO-GLI signaling
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
↑GLI1 levels
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Changes in transcription
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Tumorigenesis
 
 
 
Sonic hedgehog signaling pathway. SHH ligand binds to and inhibits the PTCH transmembrane protein. The inhibition of PTCH relieves suppression of / (Smoothened), which then activates the GLI transcription factors. The GLI proteins translocate from the cytoplasm to the nucleus, where they drive gene transcription. (Courtesy of Alexander G. Marzuka, MD),https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4445438/

Other Genetic Changes:

  • Point mutations in the TP53 gene, the tumor supressor gene are the second most common genetic alteration noticed in BCCs
  • Some mutations in the CDKN2A locus and in ras gene family (H-ras, K-ras, and N-ras) are also identified in a smaller proportion of sporadic BCCs

Enviromental Exposure

Gross and microscopic pathology

  • On gross and microscopic histopathological analysis the characteristic findings of basal cell carcinoma are described as below:
  • Basal cell carcinoma pathological features mainly depend upon the subtype. The following table summarizes them:[6][7]
Subtypes of BCC Gross features Microscopic features
Findings Images Findings Images
Nodular
M. Sand, D. Sand, C. Thrandorf, V. Paech, P. Altmeyer, F. G. Bechara [CC BY 2.0 (https://creativecommons.org/licenses/by/2.0)], via Wikimedia Commons
No machine-readable author provided. KGH assumed (based on copyright claims). [CC BY-SA 3.0 (http://creativecommons.org/licenses/by-sa/3.0/)], via Wikimedia Commons,https://upload.wikimedia.org/wikipedia/commons/b/b6/Basal_cell_carcinoma_histopathology_%283%29.jpg
Superficial
Kelly Nelson (Photographer) [Public domain], via Wikimedia Commons,https://upload.wikimedia.org/wikipedia/commons/3/32/Basal_cell_carcinoma%2C_superficial.jpg
machine-readable author provided. KGH assumed (based on copyright claims). [CC BY-SA 3.0 (http://creativecommons.org/licenses/by-sa/3.0/)], via Wikimedia Commons
Infundibulocystic
  • Well-circumscribed pearly papule
  • Most common on the head and neck region
Fibroepithelial
Morpheaform
Dermatology Centre, Salford Royal Hospital, NHS Foundation Trust, Stott Lane, Salford M6 8HD, UK.
Department of Pathology, Columbia University Medical Center, New York, USA
Infiltrative
Kelly Nelson (Photographer) [Public domain], via Wikimedia Commons,https://upload.wikimedia.org/wikipedia/commons/9/9b/Basal_cell_carcinoma_%281%29.jpg,
Micronodular
  • Multiple small aggregates of basaloid cells within the dermis, with subtle peripheral palisading and retraction artifact
Basosquamous

Video

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References

  1. Mohan SV, Chang AL (2014). "Advanced Basal Cell Carcinoma: Epidemiology and Therapeutic Innovations". Curr Dermatol Rep. 3: 40–45. doi:10.1007/s13671-014-0069-y. PMC 3931971. PMID 24587976.
  2. Pellegrini C, Maturo MG, Di Nardo L, Ciciarelli V, Gutiérrez García-Rodrigo C, Fargnoli MC (November 2017). "Understanding the Molecular Genetics of Basal Cell Carcinoma". Int J Mol Sci. 18 (11). doi:10.3390/ijms18112485. PMC 5713451. PMID 29165358.
  3. Yunoki T, Tabuchi Y, Hirano T, Miwa S, Imura J, Hayashi A (November 2018). "Gene networks in basal cell carcinoma of the eyelid, analyzed using gene expression profiling". Oncol Lett. 16 (5): 6729–6734. doi:10.3892/ol.2018.9484. PMC 6202553. PMID 30405815.
  4. Marzuka AG, Book SE (June 2015). "Basal cell carcinoma: pathogenesis, epidemiology, clinical features, diagnosis, histopathology, and management". Yale J Biol Med. 88 (2): 167–79. PMC 4445438. PMID 26029015.
  5. Montagna E, Lopes OS (2017). "Molecular basis of basal cell carcinoma". An Bras Dermatol. 92 (4): 517–520. doi:10.1590/abd1806-4841.20176544. PMC 5595599. PMID 28954101.
  6. Cameron, Michael C.; Lee, Erica; Hibler, Brian P.; Barker, Christopher A.; Mori, Shoko; Cordova, Miguel; Nehal, Kishwer S.; Rossi, Anthony M. (2019). "Basal cell carcinoma". Journal of the American Academy of Dermatology. 80 (2): 303–317. doi:10.1016/j.jaad.2018.03.060. ISSN 0190-9622.
  7. Sehgal VN, Chatterjee K, Pandhi D, Khurana A (2014). "Basal cell carcinoma: pathophysiology". Skinmed. 12 (3): 176–81. PMID 25134314.


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