Merkel Cell Carcinoma - Submitted on: Thursday February, 07, 2002

Contributed by:Artur Zembowicz, M.D., Ph.D., N/A

Merkel Cell Carcinoma has not been recognized as a separate entity until 1972, when Toker described a series of “trabecular carcinoma of the skin”. Further studies established neuroendocrine differentiation of this tumor. It is still a matter of controversy whether this tumor arises from Merkel cells or from pluripotent stem cells. Once believed to be a rare tumor, current epidemiological data indicates a significant increase in prevalence of Merkel Cell Carcinoma, which is related to aging of the population and outdoor lifestyles leading to carcinogenic effects of sun exposure

Definition: Merkel Cell Carcinoma (Neuroendocrine Carcinoma of the Skin) is an aggressive primary cutaneous neoplasms with neuroendocrine/Merkel Cell differentiation.

Clinical Features: Merkel Cell Carcinoma has predilection to individuals with fair skin. Both sexes are equally affected. It is most common in individuals in the seventh decade and older. It is most common in the head and neck region (50 %) and extremities (40%). Incidence of Merkel Cell Carcinoma is increased in immunocompromised individuals in the setting of organ transplantation. Clinical appearance is indistinguishable from other primary skin tumors. Most cases present as a single painless firm dermal nodule. Sometimes, clinical impression is that of a dermal cyst. Merkel Cell Carcinoma is one of the most aggressive cutaneous neoplasms. The local recurrence rate in Merkel Cell Carcinoma is up to 30 %. Regional lymph node metastases occur in up to 75 % of cases. Long term prognosis is poor with approximately 30 % five-year mortality rate. Distant metastases can involve lungs, internal organs, breast and brain and mucous membranes. Spontaneous regression of local and metastatic tumors has been reported. Advanced tumor stage, truncal location, age > 65 years, male sex, size of primary tumor greater then 2 cm, and long standing disease before presentation (more then 3 months) were all identified as poor prognostic factors. Prognosis in Merkel Cell Carcinoma is worse in organ transplant recipients.

Histology: Figures (Click on an image for a larger view) Figure 1. Low-magnification view of Merkel Cell Carcinoma. It shows a small blue cell tumor with pale gray low power appearance. Figure 2. High-magnification view of Merkel Cell Carcinoma. Tumor has characteristic high mitotic activity and frequent apoptotic cells Figure 3. Low-molecular keratin immunohistochemical staining in Merkel Cell Carcinoma showing characteristic paranuclear staining pattern. Examination of hematoxylin and eosin-stained sections and a panel of immunohistochemical stains establish definitive diagnosis of Merkel Cell Carcinoma. On routinely stained sections Merkel Cell Carcinoma is a dermal small blue cell tumor composed of uniform oval cells with uniform nuclei with pale vesicular of finely granular (salt and pepper-like) nuclei and scant amphophilic cytoplasm (Figure 1). Slate gray low power appearance of the tumor is characteristic. The cells form dermal nests, trabeculae or sheets. Mitotic activity is usually brisk and single cell necrosis is frequent (Figure 2). Rarely, intraepidermal component is present. It may simulate nested pattern of in situ superficial spreading melanoma with prominent pagetoid spread. Merkel Cell Carcinoma can have areas of squamous, glandular (eccrine) or even melanocytic differentiation.

Treatment: Merkel Cell Carcinoma requires a multidisciplinary approach. Local treatment is accomplished by wide local excision, best with at least 1-2 cm margin. Good success of local treatment can be achieved by Moh’s micrographic surgery. Recent data suggests better local control after adjuvant radiation therapy of the excision site. Sentinel lymph node mapping in a biopsy proven Merkel Cell Carcinoma showed 50-80% positive lymph nodes. Metastatic Merkel Cell Carcinoma has been treated successfully by high dose polychemotherapy followed by autologous blood stem cell transplantation.

Bibliography: Toker C. Trabecular carcinoma of the skin. Arch.Dermatol. 1972;105(1):107-10. Skidmore RAJ, Flowers FP. Nonmelanoma skin cancer. [Review] [55 refs]. Med.Clin.North Am. 1998;82(6):1309-23. Sibley RK, Dehner LP, Rosai J. Primary neuroendocrine (Merkel cell?) carcinoma of the skin. I. A clinicopathologic and ultrastructural study of 43 cases. Am.J.Surg.Pathol. 1985;9(2):95-108. Tai PT, Yu E, Tonita J, Gilchrist J. Merkel cell carcinoma of the skin. [Review] [190 refs]. J.Cutan.Med.Surg. 2000;4(4):186-95. Gooptu C, Woollons A, Ross J, Price M, Wojnarowska F, Morris PJ, Wall S, Bunker CB. Merkel cell carcinoma arising after therapeutic immunosuppression. Br.J.Dermatol. 1997;137(4):637-41. Haag ML, Glass LF, Fenske NA. Merkel cell carcinoma. Diagnosis and treatment. [Review] [175 refs]. Dermatol.Surg. 1995;21(8):669-83. Connelly TJ, Cribier B, Brown TJ, Yanguas I. Complete spontaneous regression of Merkel cell carcinoma: a review of the 10 reported cases. [Review] [18 refs]. Dermatol.Surg. 2000;26(9):853-6. Ott MJ, Tanabe KK, Gadd MA, Stark P, Smith BL, Finkelstein DM, Souba WW. Multimodality management of Merkel cell carcinoma. Arch.Surg. 1999;134(4):388-92. LeBoit PE, Crutcher WA, Shapiro PE. Pagetoid intraepidermal spread in Merkel cell (primary neuroendocrine) carcinoma of the skin. Am.J.Surg.Pathol. 1992;16(6):584-92 Tang CK, Toker C. Trabecular carcinoma of the skin: further clinicopathologic and ultrastructural study. Mt.Sinai J.Med. 1979;46(5):516-23. Nicholson SA, McDermott MB, Swanson PE, Wick MR. CD99 and cytokeratin-20 in small-cell and basaloid tumors of the skin. Appl.Immunohistochem.Molecul.Morphol. 2000;8(1):37-41. Chan JK, Suster S, Wenig BM, Tsang WY, Chan JB, Lau 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(2):226-34. Cheuk W, Kwan MY, Suster S, Chan JK. Immunostaining for thyroid transcription factor 1 and cytokeratin 20 aids the distinction of small cell carcinoma from Merkel cell carcinoma, but not pulmonary from extrapulmonary small cell carcinomas. Arch.Pathol.Lab.Med. 2001;125(2):228-31. 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(9):1217-23.

 

Back To Cases