CASO CLÍNICO

 

Cutaneous Merkel cell carcinoma. Case report and literature review

Carcinoma cutáneo de células de Merkel. Presentación de un caso y revisión de la literatura

 

 

J.M. López-Arcas¹, J.L. Cebrián Carretero², E. Palacios¹, J. Macarrón³, L. Pingarrón¹, G. Demaría¹, M. Burgueño⁴

1 Médicos Residentes. Servicio de Cirugía Oral y Maxilofacial.
2 FEA. Servicio de Cirugía Oral y Maxilofacial.
3 Médico Residente. Servicio de Dermatología.
4 Jefe de Servicio. Servicio de Cirugía Oral y Maxilofacial.
Hospital Universitario La Paz. Madrid, España

Correspondence

 

 

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ABSTRACT

Merkel-cell carcinoma is a rare skin cancer of neuroendocrine origin, which has been described as the most aggressive skin malignancy. The tumor arises from the Merkel cells, or skin pressure receptors. It has an infiltrative growth pattern and spreads by the lymphatic vessels and blood. It is similar to small cell lung carcinoma, with an intrinsic sensitivity to chemo-radiotherapy and a remarkable tendency to metastasize. The best treatment outcomes are obtained with early diagnosis and a combination of surgery, chemotherapy, and radiotherapy. A clinical case of Merkel cell carcinoma of the face treated with surgery and radiotherapy is reported and the literature is reviewed.

Key words: Merkel cells; Merkel cancer; Skin cancer.

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RESUMEN

El carcinoma de células de Merkel, constituye una variedad infrecuente de cáncer cutáneo, de origen neuroendocrino, que clásicamente se describe, como la malignidad cutánea de peor pronóstico. Se origina a partir de las células de Merkel o receptores cutáneos de presión. Presenta un patrón infiltrativo dermo-linfático así como extensión linfática nodal y diseminación hematógena. Presenta numerosas similitudes con el carcinoma pulmonar de células pequeñas, con una sensibilidad intrínseca a la quimio-radioterapia y un gran potencial metastático. Los mejores resultados se obtienen cuando se combina un diagnóstico precoz y el tratamiento combinado con cirugía- radio y quimioterapia. La principal dificultad que presentan estos tumores es la avanzada edad de la población en que se presentan y la localización de los mismos, que en ocasiones limitan las opciones terapéuticas disponibles. Presentamos un caso de carcinoma de células de Merkel facial, tratado con cirugía y radioterapia. Se realiza una revisión de la literatura.

Palabras clave: Células Merkel; Cáncer de piel.

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Introduction

Merkel cell carcinoma is an infrequent variety of skin cancers of neuroendocrine origin, which traditionally is described as the skin malignancy with the worst prognosis. It originates from Merkel cells, or cutaneous pressure receptors. These cells were described for the first time in 1875. They are located in the epidermal basement layer and are said to be slow action mechanoreceptors.

Merkel cell carcinoma was first described in 1975 by Toker,¹ who defined it as a trabecular cell carcinoma. Immunofluorescence studies and electronic microscopy allowed the cell of origin of this pathology to be identified in 1978.² It is, fortunately, an uncommon variety of skin cancer. Barely 2,000 cases have been reported since the initial description. It occurs in older people, the mean age of diagnosis being about 69 years;³ it is 2-3 times more frequent in men.

The etiological factors include, above all, sun exposure, as demonstrated by the fact that most lesions occur in exposed areas, especially the periorbital region. Other associated factors include: immunodeficiency, arsenic exposure, ectodermal dysplasia, and Hodgkin’s disease.⁴

Clinically it usually presents as an erythematous-purplish nodule with a shiny surface and, typically, telangiectasia. Confusion with other pathologies, like basocellular carcinoma, amelanotic melanoma or cutaneous lymphomas, is common.

It has a pattern of lymphatic dissemination that favors the appearance of numerous satellite lesions. Lymph node involvement is present in one-third of cases. Hematogenous dissemination occurs in 50% of cases in the course of the disease.

Regression of the main lesion has been documented. In 10-20% of cases, the primary tumor is not demonstrated, which is a sign of good prognosis in this case.⁵

It is generally located in the dermis and can extend to the epidermis or subcutaneous tissue. The typical cytological features include the triad: vesicular nucleus with small nucleoli, abundant mitoses, and apoptosis. Three histological variants have been described (intermediate, small cell, and trabecular), but they do not seem to have clinical relevance. ⁶

No specific staging system for Merkel cell carcinoma exists,⁷ but the tumor is generally classified as:

• Stage IA: local disease <2 cm.

• Stage IB: local disease >2 cm.

• Stage II: lymph node involvement.

• Stage III: metastatic disease.

Treatment depends on the disease stage. The treatment most generally accepted is surgical excision of the primary lesion with margins of about 2.5 cm and postoperative irradiation of the primary location and local and regional lymph node chains.

 

Case description

A 72 year-old woman was seen in our clinic for a rapidly growing, nodular, erythematous skin lesion with a shiny surface (Figs. 1 and 2) in the right cheek, that had appeared 5 months earlier and had not improved with topical treatment with low-strength corticoids prescribed progressively by her family physician. Biopsy of the lesion confirmed the diagnosis of Merkel’s tumor (Fig. 3).

No cervical lymph nodes were palpated. The preoperative blood tests, including tumor markers, was normal except for blood glucose 177. Cervical CT did not disclose cervical lymph node involvement. A skin lesion in the right malar region, coinciding with the external location of the lesion, was the only finding. Bone involvement was not observed. A whole-body scan with thoraco-abdominal CT did not reveal systemic invasion (Fig. 4).

The lesion was excised under general anesthesia with oncological margins and the skin was reconstructed with a cervicofacial rotation-sliding skin flap (Fig. 5-7).^5-7 External irradiation followed with a cumulative total dose of 60 Gy. Twelve months after surgery, a submandibular tumor was found during a scheduled follow- up visit; the FNAB revealed cervical metastasis of cutaneous Merkel cell carcinoma. Radical cervical dissection disclosed disease in two lymph nodes, neither of which presented extracapsular involvement (Fig. 8).

 

Discussion

Most patients have localized disease at the time of diagnosis, 70-80% in stage I. Lymph node involvement (Stage II) is present in 10-30% and metastatic disease in less than 5%. The case of our patient was classified initially as stage I. Given the short evolution between the date of intervention with radiation therapy and the appearance of cervical metastasis, the disease probably was initially stage II with microscopic lymph node involvement.

The most unfavorable prognostic factor with respect to the clinical evolution is the existence of lymph node involvement. For that reason, some authors recommend initial surgical treatment of cervical lymph nodes due to the risk of cervical metastasis and the poor prognosis. We chose postoperative irradiation for our patient because of the absence of clinical lymph node involvement. The authors believe that the proper approach to this type of cases should include a study by the sentinel lymph node technique to detect micrometastases.

Other factors of poor prognosis are: lower limb involvement, lesion size >2 cm, age over 60 years, and not including irradiation in the treatment.

It is important to study the extension of the disease when the diagnosis is made. The existence of satellite lesions and cutaneous spread should be investigated and lymphatic drainage chains should be palpated. Complementary studies include: CT, PET-CT and scintigraphy with marked octreotide.⁷ The thorax and liver, especially, are studied to exclude metastatic dissemination and a probable primary origin from small-cell carcinoma. Systemic involvement was not demonstrated before the first intervention or at the time of cervical metastatic recurrence in our patient.

 

Treatment

The primary objective of treatment must be the local and regional control of the primary lesion and associated lymph nodes, which improves the quality of life and reduces the risk of disease dissemination. Secondary objectives include preservation of the aesthetic appearance and function.

In our patient, because of the absence of skeletal involvement, a broad excision was made with 3-cm margins (except for the edge of the eyelid, where the margin was 2 cm), including underlying periostium to rule out the presence of bone involvement.

Stage I: Surgery and irradiation are recommended. Safety margins of 2.5 to 3 cm are recommended.^6,8,9 The mean 5-year survival is estimated to be 64%. Many authors recommend postoperative irradiation based on retrospective studies that compare patients treated with surgery alone versus patients treated with surgery and irradiation.^10-12 Irradiation should begin as soon as the surgical wound heals due to the propensity of this tumor to recur.

Our patient underwent surgery followed by radiation therapy approximately one month after the intervention.

Radiotherapy at a dose of 45- 60 Gy also has been used alone, obtaining adequate levels of local control, which supports the characterization of this tumor as radiosensitive. ^13,14 We believe that the initial surgical excision of the lesion is obligatory in any case.

Stage II: Management of the primary site is similar to stage I. If lymph node involvement exists, the 5-year survival rate falls to 47%. It is not certain whether surgical excision of the affected lymph nodes is better than radiation treatment alone. Lymph node involvement frequently appears as large lymph node clumps that may be inoperable. Lately it has become increasingly evident that chemotherapy should be added to the treatment of high risk patients, either as a radiosensitizer or as coadjuvant treatment.⁵

Stage III: The existence of disseminated disease reduces mean survival to less than 9 months. In consequence, if metastasis is diagnosed, treatment is merely palliative. Metastasis occurs in 28 to 70% in the course of the disease . The most frequent locations include: liver, bone, lung, and brain. The response to chemotherapy generally is of short duration and patients ultimately die from the disease.¹⁵

 

 

Correspondence:
Dr. José María López-Arcas Calleja
Servicio de Cirugía Oral y Maxilofacial.
Hospital Universitario La Paz.
Paseo de la Castellana 286
28046 Madrid, España
Email: drlopezarcas@tiscali.es

Recibido: 31.01.07
Aceptado: 17.09.07

 

 

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