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CASE REPORT

Merkel cell carcinoma: A rare, aggressive cancer of the skin

Epidemiologic data indicate that Merkel cell carcinoma is increasing in prevalence.
Part of the reason is thought to be an aging population with lifestyles that have included increased sun exposure.

Sally Becker, MT, PhD, PA-C

CASE

The author worked at the West Cancer Center, Odessa, Texas, when she wrote this article. She has indicated no relationships to disclose relating to the content of this article.

In October 2004, a 72-year-old white man was referred for evaluation of a mass on his right knee thought to be a melanoma. Six months earlier, he had noticed a flat, painless, moveable nodule slightly larger than a quarter in size and under the skin of his knee anterior to the patella. When the overlying skin became erythematous, his primary care physician diagnosed a superficial carbuncle and prescribed levofloxacin, 750 mg daily for 10 days. The discoloration resolved, but the nodule remained unchanged until August, when the patient underwent five-vessel coronary artery bypass graft surgery. In the hospital, the skin overlying the subcutaneous nodule again became erythematous. Levofloxacin, 500 mg for 10 days, again resolved the erythema. However, the mass began to grow after the course of levofloxacin was completed. When we initially saw the patient 59 days later, the nodule had grown into a 6.5-cm circular, fungating mass (see Figure 1). The only symptom it caused was a tingling sensation one evening, which he relieved with a washcloth soaked with hydrogen peroxide.

History The medical history was significant for coronary artery disease, diabetes mellitus, hypertension, and hyperlipidemia. Medications included lisinopril, metoprolol, digoxin, clopidogrel, aspirin, glyburide, metformin, pantoprazole, and atorvastatin. Besides the bypass surgery, the only other surgery this patient had undergone was removal of a benign cyst on the right side of his neck in 1991. Since his bypass surgery, he was feeling slightly weak and had mild ataxia. The patient was married with one grown child. He had no history of tobacco, alcohol, or illegal drug use. His father had had diabetes mellitus. There was no family history of cancer.

Physical examination The patient’s weight was 330 lbs; height, 71 inches; BP, 142/74 mm Hg; pulse, 67 beats per minute; respirations, 20 breaths per minute; temperature, 98.2°F (36.7°C). Except for the knee mass and mild ataxia, the remainder of the physical examination was normal, with no adenopathy or hepatosplenomegaly noted.

Laboratory tests The WBC count was 8,100/mm³ with a normal differential. The hemoglobin was 11.3 g/dL; hematocrit, 33.2%; platelets, 240,000/mm³; and glucose, 206 mg/dL. The results of the comprehensive metabolic profile were normal.

Radiology The results of CT of the chest, abdomen, and pelvis and a bone scan were all normal. Because of the patient’s size, brain MRI could not be done, but his ataxia continued to improve.

Diagnosis Microscopic examination of the knee lesion showed that the dermis was almost completely replaced by neoplastic cells and a reactive lymphoid infiltrate. After further testing, the reported diagnosis was small cell neuroendocrine carcinoma of the skin—more commonly called Merkel cell carcinoma (MCC) (see Table 1).

When the mass was removed, it was found mainly to involve the subcutaneous tissue and deeper portion of the skin, extending to the papillary dermis (see Figure 2). The margins were free of tumor. The maximum tumor diameter was 5.2 cm. The final diagnosis was small cell anaplastic carcinoma with neuroendocrine features, metastatic to the skin and subcutaneous tissue of the right knee.

DISCUSSION

Diagnosis of MCC by light microscopy is difficult because of its histologic similarity to other poorly differentiated small cell neoplasms (see Table 2). Special immunohistochemistry stains are used to distinguish MCC from similar neoplasms since each type of tumor has a unique staining profile.^1,2

MCC has three histologic patterns: trabecular, intermediate, and small cell.¹ Although the trabecular pattern is least common, it is the most differentiated and associated with the most favorable prognosis. The small cell type has the poorest prognosis and can be so undifferentiated that it can lose the ability to express antigens, thus explaining the negative immunohistochemical pattern of this tumor.³

Etiology MCC is an aggressive primary skin cancer in which malignant cells develop on or just beneath the skin and in hair follicles (see Figure 3).² The Merkel cell is named for a German anatomist and pathologist, Friedrich Sigmund Merkel, who discovered a particular round cell in the basal layers of the epidermis in 1875. The clear-staining MCs at the dermoepidermal junction were in close proximity to myelinated nerve fibers. Merkel postulated that these cells acted as mechanoreceptors and thus functioned as touch receptors.¹

Numerous MCs are present on the lip, hard palate, palms, finger pads, proximal nail folds, and the dorsum part of the feet. They have a predilection for perifollicular areas in the skin.⁴ MCs may modulate mechanoreception and are associated with sensory neuritis in the dermal papillae. However, only 10% arise in the epidermis; most are intradermal, extending into the subcutis.

Incidence and prevalence Since the first description of MCC by Cyril Toker in 1972, fewer than 1,300 cases have been reported in the literature; from 1986 to 1994, only 425 cases were registered in the National Cancer Institute’s SEER (Surveillance, Epidemiology, and End Results) program.⁵ MCC accounts for less than 1% of cutaneous malignancies.⁴ Merkel cell carcinoma is the most common of several names for this tumor. There are about 470 new MCC cases in the United States annually.^1,5 The average age at the time of diagnosis is 69 years;¹ only 5% of patients have been younger than 50 years.^1,5 Most studies show a male predominance, with surveillance, epidemiology, and end-results data suggesting a ratio of 2.3:1.¹ Whites have a 20-fold increased relative risk compared to blacks.⁵

Clinical features A patient with MCC typically presents with a solitary, rapidly growing, painless, firm, shiny, flesh-colored or bluish-red intracutaneous nodule. The lesion is most often on the head or neck, although any mucosal or cutaneous site may be affected. At initial diagnosis 70% to 80% of patients have localized disease, and 10% to 30% have regional lymph node involvement.^6,7 Although distant metastases are uncommon at presentation, one third to one half of patients with MCC eventually develop systemic disease.⁸ The most common sites for metastatic disease are the liver, bone, brain, lung, and skin.

MCC affects patients on areas exposed to sun and UV light, although some MCCs develop on non-sun-exposed areas. Immunosuppressed persons have an increased incidence. There are also reports of spontaneous regression.^7,9 No predisposing conditions have been consistently identified. Symptoms are typically local and related to tumor growth or lymph node involvement.

There is no uniformly accepted staging system for MCC. Most patients are staged according to a system first introduced by the Memorial Sloan-Kettering Cancer Center.¹⁰ Overall, the 2-year survival rate is 50% to 70%^8,11 (see Table 3).

Treatment Because MCC is a rare cancer, statistically significant data are not available for conclusively establishing its optimal treatment. Usually, complete, wide local excision of the primary tumor is warranted.

Only primary site and tumor size are predictive of a good outcome following local excision alone. MCC is radiosensitive and chemosensitive. Radiation therapy has been used for postoperative treatment, for primary treatment of unresectable or inoperable lesions, and for salvage treatment for recurrent disease. The choice of chemotherapy is empiric, with most regimens being based on those used for small cell carcinoma of the lung. Metastatic disease will develop in almost 50% of patients followed for 24 months.^8,11 Some locoregional recurrences can be treated with combined radiation and chemotherapy. However, chemotherapy of recurrent and metastatic disease is complicated by the older age of most patients, who can tolerate aggressive treatment poorly at best.

MCC is associated with a high incidence of other skin tumors and hematologic malignancies such as squamous cell carcinoma, basal cell carcinoma, melanoma, Bowen’s disease, and actinic keratoses. Also, MCC is more frequent and aggressive after immunosuppression, organ transplantation and B-cell neoplasia, for example.⁵

Outcome Our patient’s tumor was localized with a maximum diameter of 5.2 cm, and he had stage 1b disease. He chose systemic therapy and completed six cycles of etoposide and carboplatin, which he tolerated well. If he remains disease free for two years, his prognosis will be encouraging. A patient with MCC warrants frequent follow-up since in most cases relapse occurs within one year. A total body skin examination and palpation of lymph nodes, liver, and spleen should be emphasized. Laboratory or radiologic studies are advised to explore unusual symptoms.

REFERENCES

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