CT: THE JOURNAL OF COMPUTED TOMOGRAPHY 1987; 11:291-293 291

MERKEL CELL CARCINOMA

SUSAN MARKS, MD, D. RANDALL RADIN, MD, AND PARAKRAMA CHANDRASOMA, MD

Merkel cell carcinoma is a rare malignant neo- plasm of the skin which is locally invasive and fre- quently metastasizes to lymph nodes, liver, lungs, bone, and brain. Computed tomographic and pathologic findings in an elderly woman with Mer- kel cell carcinoma of the buttock and regional nodal metastasis are reported. The presence of cal- citonin and neuron-specific enolase within the tu- mor supports the theory thal Merkel cell carcinoma is a neuroendocrine tumor derived from the APlJD (amine precursor uptake and decarboxylase) sys- tem.

KEY WORDS:

Skin, neoplasms; Computed tomography

Merkel cell carcinoma is a recently recognized rare malignant neoplasm of the skin. The tumor usually occurs in elderly patients (mean age 68 years) with a 5 : 3 female predominance (1). It is locally invasive and frequently metastasizes to regional lymph nodes as well as distantly to liver, lungs, bone, and brain. In our review of the literature we found no case of Merkel cell tumor in which computed to- mography (CT) was utilized. We present the CT and pathologic findings of a Merkel cell carcinoma aris- ing in the buttock of an elderly woman.

From the Departments of Radiology and Surgical Pathology, Universitv of Southern California School of Medicine, Los An- geles, Caiifornia.

Address reprint requests to: D. Randall Radin, MD, Depart- ment of Radiology, Los Angeles County-USC Medical Center, 1200 North State Street, Los Angeles, California 90033.

Received October 1986. 0 1987 by Elsevim Science Publishing Co., Inc.

.X2 Vanderbilt Avenue, New York, NY 10017 0149-936x1871$3.50

CASE REPORT

A 74-year-old woman was admitted with a 6-month history of a gradually enlarging right buttock mass which had recently become ulcerated. On physical examination a round mass measuring 8 cm in di- ameter covered about one-third of the skin of the right buttock. The entire mass was ulcerated and was raised 2 to 3 cm above the surface of the skin. It seemed to be tethered to the underlying gluteal fas- cia. Admission laboratory values were remarkable only for a hemocrit of 32%. Serum calcium level was normal. CT demonstrated the local extent of the tumor as well as enlarged right inguinal lymph nodes (Figure 1). At surgery the mass was found to be invading down toward, but not into, the gluteal fascia. In addition to wide local excision of the pri- mary tumor, biopsy of the right inguinal nodes was performed.

The excision specimen was an ellipse of skin measuring 17 x 10 x 6 cm. In the center was a 9 x 8 cm fungating mass which infiltrated grossly to a depth of 3 cm. The margins of the excision were grossly free of tumor. The mass was firm with a ho- mogeneous fleshy tan appearance. Histopathologic examination of formalin and B5 fixed tissue showed the mass to be composed of sheets and bands of uniform round cells in the dermis and subcuta- neous tissue (Figure 2). No origin from the epider- mis was present. The cells were small with scant cytoplasm and indistinct cell membranes. The nu- clei were round and vesicular with a coarse chro- matin pattern and pinpoint nucleoli. There was ex- tensive nuclear pyknosis and a high mitotic rate. The cell masses were separated by fibrovascular tra- beculae that coursed through the tumor.

The light microscopic diagnosis of Merkel cell carcinoma was confirmed by immunohistochemical and ultrastructural findings. Studies performed by the immunoperoxidase technique on frozen as well as B5 fixed tissue showed strong positive staining

292 MARKS ET AL. CT: THE JOURNAL OF COMPUTED TOMOGRAPHY VOL. 11 NO. 3

FIGURE 1. CT scan shows a soft tissue mass involving the skin and subcutaneous tissue of the right buttock. Di- lated lymphatics extend from the mass through the sub- cutaneous fat to enlarged right inguinal lymph nodes.

of the tumor cells for neuron-specific enolase and weak positivity for calcitonin. Lymphoid markers were negative. Electron microscopy performed on glutaraldehyde fixed tissue showed the presence of moderate numbers of dense core granules in the 200 nanometer size range. These were found predomi- nantly adjacent to the cell membranes (Figure 3). Occasional primitive or intermediate-type junctions were present between cells. Fine needle aspiration biopsy of the inguinal mass showed an admixture of normal lymphocytes and highly primitive small round cells which resembled those in the primary

FIGURE 2. Histologic appearance of Merkel cell carci- noma showing sheets of uniform round cells with scant cytoplasm, ill-defined cell boundaries, and large round nuclei having a coarse chromatin distribution and small nucleoli. Many pyknotic nuclei and mitotic figures are present. (Hematoxylin and eosin, X160).

FIGURE 3. Electron micrograph showing two adjacent cells, containing membrane-bound dense core neurose- cretory granules in the cytoplasm.

neoplasm. This was interpreted as metastatic Mer- kel cell carcinoma in lymph node.

DISCUSSION

In 1972 Toker (2) reported five patients with a ma- lignant tumor which he named trabecular carci- noma of the skin. It was a primary skin carcinoma which resembled an anaplastic visceral carcinoma, but for which no extracutaneous primary site could be found. Subsequently this tumor was shown to contain neurosecretory granules and it was sug- gested that it arose from the Merkel cell (3). The Merkel cell is a cutaneous cell which is considered part of the APUD (amine precursor uptake and de- carboxylase) system derived from the neural crest (4). Merkel cells contain intracytoplasmic neurose- cretory granules but have no known hormonal ac- tivity. Despite morphologic and histochemical sim- ilarities between Merkel cells and the neoplastic cells of Merkel cell carcinoma, some authors have suggested that the tumor arises from intradermal progenitor cells rather than mature Merkel cells (1, 5). Because of its uncertain histogenesis, several other names have been applied to this neoplasm, including cutaneous APUDoma, (41, primary neu- roendocrine carcinoma of the skin (5), and primary small cell carcinoma of the skin (6).

The presence of calcitonin as well as neuron-spe- cific enolase in our patient’s tumor is supportive evidence that Merkel cell carcinoma is a neuroen- docrine tumor derived from APUD cells. Unfortu- nately, serum level of calcitonin was not measured in our patient. At least one previously reported pa- tient with Merkel cell carcinoma had elevated serum calcitonin; total thyroidectomy revealed nei-

JULY 1987 MERKEL CELL CARCINOMA 293

ther medullary carcinoma nor C cell hyperplasia (7). One other patient with hormonally active Mer- kel cell carcinoma has been described: a high con- tent of ACTH was found both in tumor tissue and in peripheral blood in a woman with elevated plasma cortisol but no clinical evidence of Cush- ing’s syndrome; no additional neoplasm was dis- covered at autopsy (8).

Raaf et al. (1) reviewed 80 patients with Merkel cell carcinoma and found the most common pri- mary tumor sites to be the head and neck (44 per- cent), leg (28 percent), arm (16 percent), and but- tock (9 percent). Because of a very high local recurrence rate of 36 percent, they recommend wide local excision when feasible. They further suggest that healthy patients undergo prophylactic regional lymph node dissection in view of the fact that 53 percent of the 80 patients eventually developed re- gional metastasis. Precise data regarding long-term survival are not available due to limited follow-up of some of the patients reviewed. However, at least 28 percent of the patients developed distant metas- tases to liver, lungs, bone, brain, or remote lymph nodes. Both radiation therapy and chemotherapy have provided palliation for metastatic disease.

The role of CT in both the initial staging and posttreatment follow-up of a wide variety of vis- ceral malignancies is well-established. We predict a similar role for CT in patients with Merkel cell car- cinoma. Findings in our patients suggest that CT can depict the extent of local tumor growth as well as enlargement of regional lymph nodes. Increasing awareness of this interesting tumor on the part of dermatologists and pathologists will result in an in- crease in the number of recognized cases. We ex- pect that CT will be indispensable in both planning and evaluating therapy for this disease.

REFERENCES 1. Raaf JH, Urmacher C, Knapper WK, et al: Trabecular (Merkel

cell) carcinoma of the skin: Treatment of primary, recurrent, and metastatic disease. Cancer 1986;57:178-182.

2. Toker C: Trabecular carcinoma of the skin. Arch Dermatol 1972;105:107-10.

3. Tang C, Toker C: Trabecular carcinoma of the skin: An ultra- structural study. Cancer 1978;42:2311-21.

4.

5.

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8.

De Wolf-Peeters C, Marien K, Mebis J, Desmet V: A cutaneous APUDoma or Merkel cell tumor? Cancer 1980;46:1810-6.

Wick MR, Goellner JR, Scheithauer BW, et al: Primary neu- roendocrine carcinomas of the skin (Merkel cell tumors): A clinical, histologic, and ultrastructural study of thirteen cases. Am J Clin Path01 1983;79:6-13. Taxy JB, Ettinger DS, Wharam MD: Primary small cell carci- noma of the skin. Cancer 1980;46:2308-11. Johannessen JV, Gould VE: Neuroendocrine skin carcinoma associated with calcitonin production: A Merkel cell carci- noma? Hum Path01 1980;11(1):586-9. Iwasaki H, Mitsui T, Kikuchi M, et al: Neuroendocrine carci- noma (trabecular carcinoma] of the skin with ectopic ACTH production. Cancer 1981;48:753-6.

CONTINUING MEDICAL EDUCATION QUESTIONS

1. Which of the following statements concerning Merkel cell carcinoma is false? a. Most patients are over 50 years of age b. Women are affected more frequently than men c. It follows an indolent course and rarely metastas-

izes d. It occurs more commonly on the head and neck or

extremities than on the trunk 2. Merkel cell carcinoma frequently metastasizes to:

a. Liver. b. Bone. c. Brain. d. All the above.

3. Evidence that Merkel cell carcinoma is a neuroendo- crine tumor derived from APUD cells includes a, The presence of neuron-specific enolase in tumor

tissue. b. Ectopic production of ACTH by the tumor. c. Ectopic production of calcitonin by the tumor. d. All the above.

4. Which of the following statements concerning Merkel cell carcinoma is false? a. Its histologic appearance may be mistaken for met-

astatic carcinoma. b. Neurosecretory granules are demonstrated by elec-

tron microscopy. c. Wide local excision and regional lymph node dis-

section are recommended as the treatment of choice.

d. There is no effective palliation for metastatic dis- ease.