Merkel cell carcinoma of the skin  (primary neuroendocrine cell carcinoma of the skin)

Clinical features

Typically a rapidly growing lesion on sun-damaged skin of the head and neck or extremities of the elderly10. Clinical diagnoses are commonly erroneous. Merkel cell carcinoma may occasionally occur in the vulva or at extra-cutaneous sites such as the oesophagus or vagina9.  

Immunosuppression-associated accounts for nearly 8% of patients with Merkel cell carcinoma .  The risk for Merkel cell carcinoma  is increased 13-fold among HIV patients, 12 and 10-fold after solid organ transplantation.  It is also found to be more common among patients with lymphoma and those receiving immunosuppressive therapy13.  A novel polyoma virus (Merkel cell polyomavirus) that is clonally integrated at various sites in the genome of the majority of Merkel cell carcinomas13.

Histopathology

Most cases show the morphology of small cell carcinoma, comprising cells with scant cytoplasm, finely stippled nuclear chromatin and high mitotic and apoptotic rates. Some have larger cells with vesicular nuclei and may show a starry sky appearance, resembling haematological malignancies.

Merkel cell tumours are commonly associated with other skin lesions, including actinic keratoses, Bowen's disease, squamous cell carcinomas and basal cell carcinomas.

Immunohistochemistry

Differential diagnosis

• metastatic small cell carcinoma from a primary in the lung or other site: positive for TTF-1 and CK7 but negative for CK20

• acute lymphoblastic lymphoma

• granulocytic sarcoma

• NT/T-cell lymphoma

Note that both Merkel cell carcinoma and haematological malignancies may be positive for CD56, bcl-2, CD117, CD99, TdT and CD10. CK20, neuroendocrine markers (chromogranin, synaptophysin) and other lymphoid markers (CD45, CD3, CD20 and CD34) will distinguish.

• small cell malignant melanoma

Prognosis

Poor: in one series, 60% of patients had local recurrences or metastases at follow up5. Regional metastases occur in up to 75% of patients. Five year survival is between 30% and 64%. Male patients have a worse prognosis10. Size greater than 30 mm, stage II disease, absence of an inflammatory infiltrate and more than 50% of tumour cells being positive for Ki67 are markers of poor prognosis12.

References

1 Chan JKC et al. Cytokeratin 20 immunoreactivity distinguishes Merkel cell (primary cutaneous neuroendocrine) carcinomas and salivary gland small cell carcinomas from small cell carcinomas of various sites. Am J Surg Pathol 1997;21:226-234.

2 Byrd-Gloster AL, Khoor A, Glass LF, et al. Differential expression of thyroid transcription factor 1 in small cell lung carcinoma and Merkel cell tumor. Hum Pathol 2000; 31:58-62

3 Ordonez NG. Value of thyroid transcription factor-1 immunostaining in distinguishing small cell lung carcinomas from other small cell carcinomas. Am J Surg Pathol 2000;24:1217-1223.

4 Cheuk W et al. Immunostaining for thyroid transcription factor-1 and cytokeratin 20 aids in the distinction of small cell carcinoma from Merkel cell carcinoma, but not pulmonary from extrapulmonary small cell carcinoma. Arch Pathol Lab Med 2001;125:228-231.

5 Walsh, N. M. Primary neuroendocrine (Merkel cell) carcinoma of the skin: morphologic diversity and implications thereof. Hum Pathol 2001;32:680-689.

6 Leech, S. N., Kolar, A. J., Barrett, P. D., Sinclair, S. A., Leonard, N. Merkel cell carcinoma can be distinguished from metastatic small cell carcinoma using antibodies to cytokeratin 20 and thyroid transcription factor 1. J Clin Pathol 2001;54:727-729

7 Erickson, L. A. and R. V. Lloyd (2004). "Practical markers used in the diagnosis of endocrine tumors." Adv Anat Pathol 11(4): 175-89.

8 Dong HY, Liu W, Cohen P, et al. B-cell specific activation protein encoded by the PAX-5 gene is commonly expressed in merkel cell carcinoma and small cell carcinomas. Am J Surg Pathol 2005; 29:687-92

9 Coleman NM, Smith-Zagone MJ, Tanyi J, et al. Primary neuroendocrine carcinoma of the vagina with Merkel cell carcinoma phenotype. Am J Surg Pathol 2006; 30:405-10

10 Sur M, Alardati H, Ross C, et al. TdT expression in Merkel cell carcinoma: potential diagnostic pitfall with blastic hematological malignancies and expanded immunohistochemical analysis. Mod Pathol 2007; 20:1113-20

11 Battifora H,Silva EG The use of antikeratin antibodies in the immunohistochemical distinction between neuroendocrine (Merkel cell) carcinoma of the skin, lymphoma, and oat cell carcinoma. Cancer 1986; 58:1040-6

12 Llombart B, Monteagudo C, Lopez-Guerrero JA, et al. Clinicopathological and immunohistochemical analysis of 20 cases of Merkel cell carcinoma in search of prognostic markers. Histopathology 2005; 46:622-34

 13 Busam KJ, Jungbluth AA, Rekthman N, Coit D, Pulitzer M, Bini J, et al. Merkel cell polyomavirus expression in merkel cell carcinomas and its absence in combined tumors and pulmonary neuroendocrine carcinomas. Am J Surg Pathol. 2009 Sep;33(9):1378-85.

14 Ralston J, Chiriboga L, Nonaka D. MASH1: a useful marker in differentiating pulmonary small cell carcinoma from Merkel cell carcinoma. Mod Pathol. 2008 Nov;21(11):1357-62.

15 Sierakowski A, Al-Janabi K, Dam H, Sood M. Metastatic Merkel cell carcinoma with positive expression of thyroid transcription factor-1--a case report. Am J Dermatopathol. 2009 Jun;31(4):384-6.

This page last revised 31.1.2010.