Unknown primary Merkel cell carcinoma: 23 new cases and a review

doi:10.1016/j.jaad.2012.07.035

Journal of the American Academy of Dermatology

Volume 68, Issue 3, March 2013, Pages 433-440

Presented in poster format at the Annual Meeting of the American College of Mohs Surgery in New York City, New York, May 2, 2010.

https://doi.org/10.1016/j.jaad.2012.07.035 Get rights and content

Background

Knowledge is limited regarding unknown primary Merkel cell carcinoma (UPMCC).

Objective

We sought to document the characteristics and behavior of UPMCC, and determine the most appropriate treatment.

Methods

A multicenter, retrospective, consecutive study reviewing patients given a diagnosis of UPMCC between 1981 and 2008 was completed. In addition, a literature review of cases of UPMCC was performed.

Results

In all, 23 patients with UPMCC are described and 34 cases from previous reports are compiled. Among the 23 new cases of UPMCC, the average age at diagnosis was 66.0 years; the majority of patients were male (87%) and Caucasian (100% of those reported). One patient was immunosuppressed, and 39% had a history of other cancer. After the initial biopsy, 16 patients had further evaluation of the involved lymph node basin. Half of these had additional positive nodes (8 of 16). The majority of patients had lymph node basin involvement only (78%), whereas 22% had lymph node basin and distant metastasis. The most common lymph node basin involved was inguinal. The median size of the involved lymph node at diagnosis was 5.0 cm. At 2 years, the overall survival of stage IIIB UPMCC was significantly improved versus stage IIIB known primary Merkel cell carcinoma (MCC): 76.9% to 36.4%.

Limitations

Limited number of cases and retrospective review are limitations.

Conclusion

Our data demonstrate improved overall survival in patients with stage IIIB UPMCC versus those with stage IIIB known primary MCC. Because of the unpredictable natural history of UPMCC, we recommend individualization of care based on the details of each patient’s clinical presentation.

Section snippets

Methods

The Institutional Review Board at Mayo Clinic, Rochester, Minn, approved this study. A search was performed of the institution’s diagnostic index database for all consultation cases of MCC at Mayo Clinic in Rochester, Minn; Scottsdale, Ariz; and Jacksonville, Fla, from 1981 to 2008. The most recent patient included was given a diagnosis in October 2008. This resulted in at least 1 potential year of follow-up from the time of treatment. In each case, a Mayo Clinic dermatopathologist or surgical

Results

A total of 23 patients with UPMCC diagnosed between 1981 and October 2008 were analyzed. The first patient included was given a diagnosis in October 1990, and the most recent patient included was given a diagnosis in October 2008. Of interest, 1 UPMCC was encountered per year except for years 2001 through 2004, when there were 3 cases per year.

The average age of diagnosis was 66.0 years (SD 10.4, range 39-84). There was a predominance of male patients at 87% (20), and 100% (15) were Caucasian

Discussion

There are a limited number of case reports and series in the literature detailing UPMCC. These data now represent one of the largest collections in the literature to our knowledge. Similar to other cases, our group tended to be elderly, Caucasian men. Our findings agree with a previous report that concluded patients without an identifiable primary have an improved overall survival and decreased risk of death secondary to disease.⁴¹ We found a statistically significant improvement in overall

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Neuroendocrine neoplasms (NENs) are a heterogeneous group of tumors arising from the transformation of neuroendocrine cells in several organs, most notably the gastro-entero-pancreatic system and respiratory tract. The classification was recently revised in the 5th Edition of the WHO Classification of Endocrine and Neuroendocrine Tumors. NENs can rarely spread to the central or peripheral nervous systems. Neurologic involvement is determined by the rare development of paraneoplastic syndromes, which are remote effects of cancer. Mechanisms depend on immunologic response to a tumor, leading to the immune attack on the nervous system or the production of biologically active (“functioning”) substances, which can determine humoral (endocrine) effects with neurologic manifestations. Paraneoplastic neurologic syndromes (PNS) are immunologically mediated and frequently detected in small cell lung cancer but rarely seen in other forms of NEN. PNS and Merkel cell carcinoma is increasingly reported, especially with Lambert Eaton myasthenic syndrome. Endocrine manifestations are found in a wide spectrum of NENs. They can develop at any stage of the diseases and determine neurologic manifestations. Patient outcomes are influenced by tumor prognosis, neurologic complications, and the severity of endocrine effects.
Merkel cell carcinoma and the eye
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Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine tumor with a poor five-year survival rate. Yearly cases have risen nearly 350% since the early 1980s, and these are predicted to increase as the overall US population ages. MCC of the eyelid is uncommon and can be misdiagnosed as other benign inflammatory and neoplastic eyelid disorders. Although MCC of the head and neck is often more aggressive than it is at other sites, eyelid MCC shows a lower disease-specific mortality rate. A biopsy is essential for accurate diagnosis, including an immunohistochemical panel of CK20 and TTF-1, although other markers may be necessary. Staging can be assessed clinically through physical examination findings and imaging and/or pathologically with sentinel lymph node biopsy or fine-needle aspiration. Pathologic staging more accurately predicts the prognosis. Eyelid MCC treatments include Mohs micrographic surgery to allow for complete clearance and adequate reconstruction of lost tissue, followed by adjuvant radiotherapy. In advanced disease, immunotherapies are preferred over traditional chemotherapy and are a subject of ongoing research.
Abdominal metastases from Merkel cell carcinoma: Prevalence and presentation on CT examination in 111 patients
2022, Diagnostic and Interventional Imaging
The purpose of this study was to report the prevalence and imaging features of abdominal metastases from Merkel cell carcinoma (MCC) on computed tomography (CT) examinations.
A total of 111 patients with MCC from two institutions were initially identified. Of these, 27 patients (27/111; 24.3%) had abdominal metastases from MCC present on CT examination. There were 19 men and 8 women with a mean age of 75 ± 10.8 (SD) years (age range: 46–92 years). CT examinations were retrospectively reviewed by two radiologists and analyzed quantitatively for the number and dimensions of abdominal metastases from MCC and qualitatively in terms of location, margins, contours, homogeneity, patterns of enhancement, vascular involvement and extension of metastases from MCC.
Fifteen patients (15/27; 56%) had abdominal metastatic disease at initial diagnosis and twelve (12/27; 44%) developed abdominal metastases during the course of the disease. The mean number of locations of abdominal metastases was 2.1 ± 1.12 (SD) (range: 1–5). Abdominal metastases involved abdominal lymph nodes (16/27; 59%), adrenal glands/kidneys/retroperitoneum (14/27; 52%), mesentery/peritoneum (13/27; 48%), liver (7/27; 26%) and pancreas (7/27; 26%). Vascular involvement was found in association with peritoneal/mesenteric metastases in 6/13 (46%) patients with intraperitoneal metastases or in association with abdominal lymph nodes in 4/16 (25%) patients. Ureteral encasement and/or dilatation was found in 4/14 (28%) patients with retroperitoneal metastases and 3/16 (19%) patients with abdominal lymph nodes. Metastases to the liver, pancreas, peritoneum, retroperitoneum and adrenal glands displayed internal enhancement during the arterial phase in 1/2 (50%), 4/5 (80%), 4/7 (57%) and 5/8 (62%) patients for whom arterial phase was available, respectively.
: Metastases from MCC have a prevalence of 24.3% on CT examination and may involve a variety of abdominal organs, mainly lymph nodes, peritoneal and retroperitoneal structures, but also the liver and pancreas. CT features of abdominal metastases from MCC include hypervascularity during the arterial phase of enhancement and eventually vascular and ureteral involvement.
Tumor primary site as a prognostic factor for Merkel cell carcinoma disease-specific death
2021, Journal of the American Academy of Dermatology
Merkel cell carcinoma (MCC) primary site has not been fully investigated as a potential prognostic factor.
To determine the incidence by tumor primary site of death due to MCC.
We undertook a retrospective analysis of the Survival, Epidemiology, and End Results database. MCC patients treated between 1973 and 2016 were grouped by tumor primary site and a competing risks analysis was performed to test the impact of primary site on disease-specific death. Cumulative incidence of Merkel cell carcinoma-specific mortality (CMMI) at 5 years was estimated for each primary site.
Of 9407 MCC patients identified, 6305 (67.0%) had localized disease, 2397 (25.5%) had regional metastasis, and 705 (7.5%) had distant metastasis. Tumor primary site was predictive of CMMI and varied by stage at diagnosis. Tumors involving the scalp/neck carried the highest CMMI among localized MCC (26.0%). Tumors involving the lip had the highest CMMI among MCC with regional metastasis (56.7%) and distant metastasis (82.1%).
Tumor size data were missing for a large proportion of patients, precluding stratification by stage according to current American Joint Committee on Cancer guidelines.
Probability of MCC disease-specific death varies by primary site. The primary site of the tumor may be useful as a prognostic indicator for MCC.
Surgical Management of Merkel Cell Carcinoma
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Citation Excerpt :
A full-body dermatologic survey and whole-body PET-CT scan are helpful in staging and work-up (Fig. 3). UP MCC is characterized by infrequent intradermal metastases and portends a more favorable survival than other MCCs with similar nodal disease burden levels.49 UP MCC has a lower association with MCC polyomavirus than with cutaneous MCC.50
Does regional lymph node status have a predictive effect on the prognosis of Merkel cell carcinoma?
2021, Journal of Plastic, Reconstructive and Aesthetic Surgery
There is no article that studies whether the regional lymph node (RLN) status affects the prognosis of Merkel cell carcinoma (MCC).
The survival and disease data of MCC patients were obtained from the Surveillance, Epidemiological, and End Results (SEER) database. The overall survival (OS) and cause-specific survival (CSS) rates were endpoints.
A total of 1822 patients were included, with a mean age of 72.5 years. The number of RLN-positive patients was 862 (47.3%), and the number of RLN-negative patients was 960 (52.7%). The regression analysis showed that primary site, sex, and tumor size were statistically significant and independent predictors of RLN status. The five-year OS and CSS of RLN-negative patients were 71.4% and 92.3%, respectively, which were much higher than those of RLN-positive patients (37.5% and 65.8%, respectively) (P <0.001). In univariate survival analysis, positive RLN significantly predicted deterioration of OS and MSS (P <0.001). In multivariate analysis, RLN status had no statistically significant effect on patient prognosis.
The prognosis of patients with RLN metastasis is worse than that of patients without RLN metastasis, but RLN status is not an independent predictor of the prognosis of patients with MCC.

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: Funding sources: None.

: Conflicts of interest: None declared.

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Original articleUnknown primary Merkel cell carcinoma: 23 new cases and a review

Background

Objective

Methods

Results

Limitations

Conclusion

Section snippets

Methods

Results

Discussion

Int J Radiat Oncol Biol Phys

J Am Acad Dermatol

J Am Acad Dermatol

Pathol Res Pract

Am J Otolaryngol

J Am Acad Dermatol

J Am Acad Dermatol

Trabecular carcinoma of the skin

Arch Dermatol

Clonal integration of a polyomavirus in human Merkel cell carcinoma

Science

Adjuvant local irradiation for Merkel cell carcinoma

Arch Dermatol

Five hundred patients with Merkel cell carcinoma evaluated at a single institution [Erratum in Ann Surg 2012;255:404]

Ann Surg

Chronic lymphocytic leukemia is associated with decreased survival of patients with malignant melanoma and Merkel cell carcinoma in a SEER population-based study

J Clin Oncol

Adjuvant radiation therapy is associated with improved survival in Merkel cell carcinoma of the skin

J Clin Oncol

Merkel cell carcinoma: improved outcome with the addition of adjuvant therapy

J Clin Oncol

Merkel cell carcinoma: prognosis and treatment of patients from a single institution

J Clin Oncol

The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM

Ann Surg Oncol

Merkel cell tumor of the skin

Hum Pathol

Merkel cell tumor-like neuroendocrine carcinoma associated with the submandibular gland: report of a case with cytologic, immunohistochemical, electron microscopic and flow cytometric studies

Acta Cytol

Lymph node metastases of a Merkel-cell tumor of unknown origin: possibilities and limitations of fine-needle aspiration cytology

Pathologica

Merkel cell tumor of the head and neck: five new cases with literature review

Arch Otolaryngol Head Neck Surg

Original article
Unknown primary Merkel cell carcinoma: 23 new cases and a review