Merkel cell carcinoma (neuroendocrine cancer of skin, trabecular cancer)
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Introduction
Rare aggressive cutaneous neoplasm.
Etiology
- polyomavirus[4] (Merkel cell virus)
- risk factors
- exposure to sunlight
- immunosuppression
- exposure to arsenic
- older age
Epidemiology
- rare, 2000 cases in the U.S. yearly
- occurs mostly in people after age 70
- majority of patients are white
- occurs more often in men than women
- cause of death of Jimmy Buffet September 1, 2023
Pathology
- Merkel cells located in the basal layer of the epidermis & hair follicle or
- immature totipotential stem cells that acquire neuroendocrine features during transformation
- majority of tumors are intradermal as opposed to epidermal
- frequent metastases to regional lymph nodes
- commonly involved metastatic sites include liver, bone, brain & skin
Microscopic pathology
- histologically similar to other poorly differentiated neoplasms
- histologic patterns
- trabecular type
- small cell type
- intermediate type (most common)
Immunophenotype
- cytokeratin: +
- CK20: + 97%
- CK7: -/+ (23% positive[3])
- Ber-EP4: +
- EMA: + 78%
- thyroid transcription factor 1: -
- neuroendocrine markers: +
- S100: -
- high molecular weight cytokeratins: -
- NSE: -
- chromogranin A: + 72%
- chromogranin B: + 100%
- synaptophysin: + 39%
- CD99: +/-
Genetics
- chromosome 1p abnormalities in ~40%
- p53 mutations
- p73 mutations
- loss of heterozygosity 3p21
- genomic integration of Merkel cell polyomavirus (80%)
* Merkel cell polyomavirus does not always lead to Merkel cell carcinoma
Clinical manifestations
- rapidly growing painless firm nontender nodule
- red, pink, or blue nodules
- variable size from < 1/4 inch to > 2 inches
- ~2% present with nodal or metastatic disease without apparent skin primary
- ~1/3 - 1/2 eventually develop systemic disease
- predilection for sun-exposed areas
* image[8]
Laboratory
- tumor biopsy & sentinel lymph node biopsy
- complete blood count
- liver function tests
Radiology
- CT scan to rule out metastases
Management
- surgical resection
- sentinel lymph node biopsy
- for early stage disease with negative sentinel lymph node biopsy Mohs micrographic surgery is associated with significantly improved overall survival compared with wide local excision[11]
- adjunctive radiation therapy may be useful[6]
- chemotherapy NOT curative [4]
- avelumab (Bavencio) FDA-approved for metastatic Merkel cell carcinoma March 2017[7]
- pembrolizumab (Keytruda) for metastatic Merkel cell[1]; FDA-approved[10]
- neoadjuvant nivolumab may reduced extent of surgical resection needed[9]
- prognosis
- 5-year survival is 75% if localized, 61% if regional, 24% if metastatic
More general terms
References
- ↑ 1.0 1.1 UpToDate http://uptodateonline.com/application/topic.asp?file=skin_can/7766&type=A&selectedTitle=24~42
- ↑ Dabbs. Diagnostic Immunohistochemistry. Churchill-Livingstone, 2002. page 233.
- ↑ 3.0 3.1 Jensen et al. Appl Immunohisstochem Mol Morphol 8:310-5, 2000 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11127923
- ↑ 4.0 4.1 4.2 Feng H et al, Clonal integration of a polyoma virus in human Merkel cell carcinoma. Science 2008, Jan 17 ePub PMID: https://www.ncbi.nlm.nih.gov/pubmed/18202256
- ↑ Touze A et al. High levels of antibodies against Merkel cell polyomavirus identify a subset of patients with Merkel cell carcinoma with better clinical outcome. J Clin Oncol 2011 Apr 20; 29:1612. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21422439
Paulson KG et al. Transcriptome-wide studies of Merkel cell carcinoma and validation of intratumoral CD8+ lymphocyte invasion as an independent predictor of survival. J Clin Oncol 2011 Apr 20; 29:1539. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21422430 - ↑ 6.0 6.1 Kim JA and Choi AH. Effect of radiation therapy on survival in patients with resected Merkel cell carcinoma: A propensity score surveillance, epidemiology, and end results database analysis. JAMA Dermatol 2013 Jul; 149:831 PMID: https://www.ncbi.nlm.nih.gov/pubmed/23864085
- ↑ 7.0 7.1 Bankhead C FDA Approves Drug for Rare Skin Cancer.
Avelumab active in Merkel cell carcinoma. MedPage Today. March 23, 2017 https://www.medpagetoday.com/Dermatology/SkinCancer/64096 - ↑ 8.0 8.1 Stokowsk LA Merkel Cell Carcinoma: Not Just Another Skin Cancer. An Interview With Paul Nghiem, MD, PhD Medscape. Oct 27, 2017. https://www.medscape.com/viewarticle/886140
- ↑ 9.0 9.1 Kuznar W with expert critique by Klil-Drori AJ Neoadjuvant Nivolumab Tames Resectable Merkel Cell Carcinoma. May reduce the extent of surgery required. MedPage Today. ASCO Reading Room 11.24.2018 https://www.medpagetoday.com/reading-room/asco/skin-cancer/76465
- ↑ 10.0 10.1 Kuznar W with critique by Hermel D Pembrolizumab Approved in Merkel Cell Carcinoma: Higher Response Rates, Less Toxicity Compared With Chemotherapy. Accelerated approval for both adults and children with recurrent locally advanced or metastatic disease. MedPage Today. ASCO Reading Room 01.26.2019 https://www.medpagetoday.com/reading-room/asco/skin-cancer/77620
- ↑ 11.0 11.1 Cheraghlou S, Doudican NA, Criscito MC et al Overall Survival After Mohs Surgery for Early-Stage Merkel Cell Carcinoma. JAMA Dermatol. Published online August 23, 2023. PMID: https://www.ncbi.nlm.nih.gov/pubmed/37610773 PMCID: PMC10448369 Free PMC article https://jamanetwork.com/journals/jamadermatology/fullarticle/2808884
- ↑ Wikipedia: Jimmy Buffett https://en.wikipedia.org/wiki/Jimmy_Buffett
- ↑ Merkel Cell Cancer http://cis.nci.nih.gov/fact/6_11.htm
- ↑ Merkel Cell Carcinoma (PDQ): Treatment http://www.nci.nih.gov/cancerinfo/pdq/treatment/merkelcell/patient/