Journal of Cancer Research and Therapeutics Medknow Publications on behalf of the Association of Radiation Oncologists of India (AROI) ISSN: 0973-1482 EISSN: 1998-4138 Vol. 6, Num. 3, 2010, pp. 382-384

Journal of Cancer Research and Therapeutics, Vol. 6, No. 3, July-September, 2010, pp. 382-384

Case Report

Remission of Merkel cell tumor after somatostatin analog treatment

M Fakiha, P Letertre, JP Vuillez, J Lebeau

Department of Plastic and Maxillofacial Surgery, CHU-Grenoble Hospital, Grenoble, France

Correspondence Address:M Fakiha, 7 rue de l'oisans, 38240 Meylan, France, dr_fakiha@yahoo.com

Code Number: cr10095

PMID: 21119285

DOI: 10.4103/0973-1482.73352

Abstract

Keywords: Merkel cell carcinoma, somatostatin analogues, octreoscan, Lanreotide

Introduction

Merkel cell carcinoma is a highly aggressive cancer with 30% mortality. To date, there is no standard protocol for the management of MCC. Surgical treatment of large tumor especially in the head and neck region can be disfiguring. We present a medical treatment for a non- operable case with complete remission without side effects.

Case Report

An 87-years-old female patient was referred to the plastic and maxillo-facial surgery unit after the third recurrence of MCC of the forehead [Figure - 1]. The disease was discovered five months earlier and had recurred very rapidly after each of three surgical excisions with 1 cm margin. The histopathological aspects and immunohistochemical markers confirmed the diagnosis. Clinical examination revealed one enlarged right upper lateral cervical lymph nodes that were hard, painless and mobile.

The octreoscan showed a highly significant uptake in the frontal and cervical regions as well as a focus at the right pulmonary apex [Figure - 2].

The case was submitted to the local cancer research and treatment commission. A treatment by lanreotide (BIM 23014, Ipsen International) was elected at the dose of 15 mg. I.M. injection every two weeks.

A primary appraisal of the treatment was done after two months. Clinically all perceptible frontal and cervical lesions had completely disappeared [Figure - 3]. A small zone of superficial frontal ulceration persisted, a biopsy revealed a common lymphoplasmocytic inflammatory granuloma. A control octreoscan was done 15 days after the last lanreotide injection. The frontal and cervical uptake had completely disappeared [Figure - 4] However, the right pulmonary apex focus had persisted, a CT-scan of this area failed to show any anatomical lesion. The nature of this uptake zone remained uncertain. The tolerance of the treatment was apparently excellent, no side effects had been observed. At this stage, we decided to continue the lanreotide injections at the same rate with monthly follow up.

Seven months after the first injection, a new, hard, painless, upper lateral cervical lymph node was discovered. Again the octreoscan was positive and the diagnosis of Merkel cell tumor recurrence was confirmed by an excision-biopsy under local anesthesia. Another immediate postoperative octreoscan showed complete resolution of the preoperative cervical uptake. After this recurrence under lanreotide therapy, we decided to stop the treatment. The follow-up after 17 months of the first lanreotide injection (10 months after excision of the recurrent cervical metastasis) is negative for local relapse and metastases. The octreoscan control is also negative except for the unchanged right pulmonary uptake.

Discussion

Merkel cell carcinoma is a highly aggressive cancer with 30% mortality. The incidence in the united state has increased three- fold and become the second most common cause of non-melanoma skin cancer death. ^[1],[2]

The most common clinical features were used to create an acronym: AEIOU: asymptomatic/lack of tenderness, expanding rapidly (< 3 months), i mmunosuppression, older than 50, and location on an ultraviolet-exposed site. These criteria may be serving as a clue in the diagnosis of MCC. In a clinical series of 195 patients, 89% met three or more criteria. ^[3]

MCC is presented as primary disease only (stage 1) in 75%, with regional nodal disease (stage 2) in 21 %, and with distant disease (stage 3) in 4%. ^[4]

The diagnosis is confirmed by histopathological examination using an immunohistochemical study. The use of scintigraphy (octreoscan) helps in the determination of local extend and tumor metastasis (see later).

The treatment options of this specific type of skin cancer are: surgical excision with negative margins with or without sentinel lymph node biopsy. The role of adjuvant therapy is controversial with more evident support of the use of adjuvant radiotherapy but not chemotherapy. ^[5] To date, there is no standard protocol for the management of MCC.

The Therapeutic role of Somatostatin

Somatostatine has been discovered in 1968 in the course of research on the distribution of GHRH in rat′s hypothalamus. This hormone has multiple actions:

Endocrine action: Its principal role is to inhibit the synthesis and the release of hypophyseal GH. It also inhibits endocrine secretions of the gastro-intestinal tract and the pancreas.

Paracrine action: It suppresses the synthesis of local growth factors. ^[6],[7]

The direct antiproliferative action is mediated by high affinity somatostatin specific receptors. Five sub-types of these receptors have been discovered. ^[8] Somatostatin analogs have been used for the past few years as a palliative treatment of secretary neuro-endocrine tumors with a remarkable symptomatic efficiency

Moreover, the amplitude of the anti-proliferative action correlates with the number of receptors present on the tumor surface. ^[9] Each type of tumor shows different sub-types of somatostatin receptors.

As for Merkel cell tumors, being non-secretory, only the anti-proliferative effect is of interest.

There are some cases of tumor melting in another neuroendocrine tumor. REUBI explain these phenomena by the strong presence of receptors sensitive to somatostatin in the per-tumoral veins which cause a local vasoconstriction which leads to tumor necrosis.

We think this is a possible mechanism in our patients due to the rapidity of tumor size reduction (necrosis).

Spontaneous regression of MCC has been reported in the literatures. Eighteen cases of complete or partial regression were found. The mechanism is unknown, though this spontaneous regression was attributed most likely to apoptosis and cell-mediated immunity. ^[10] Cirillo reported a complete remission of a metastatic MCC in a male patient after treatment with octreotide for 10 months. ^[11]

With somatostatin analog (lanreotide) treatment in our patient, we had an excellent initial response (though another lesion discovered under treatment). We have a follow up period of 17 months since the start of the treatment and the patient has a normal quality of life without recurrence.

References

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