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Table of Contents
CASE REPORT
Year : 2010  |  Volume : 6  |  Issue : 3  |  Page : 382-384
 

Remission of Merkel cell tumor after somatostatin analog treatment


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

Date of Web Publication29-Nov-2010

Correspondence Address:
M Fakiha
7 rue de l'oisans, 38240 Meylan
France
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DOI: 10.4103/0973-1482.73352

PMID: 21119285

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 > Abstract 

We recently treated one patient presenting with a disseminated non-operable Merkel cell carcinoma (MCC) by lanreotide (somatostatin analog), with a complete remission of the disease and a follow up of 17 months. We present in this paper a case report with a review of the utilization of somatostatin analogues in the treatment of MCC.


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


How to cite this article:
Fakiha M, Letertre P, Vuillez J P, Lebeau J. Remission of Merkel cell tumor after somatostatin analog treatment. J Can Res Ther 2010;6:382-4

How to cite this URL:
Fakiha M, Letertre P, Vuillez J P, Lebeau J. Remission of Merkel cell tumor after somatostatin analog treatment. J Can Res Ther [serial online] 2010 [cited 2014 Apr 24];6:382-4. Available from: http://www.cancerjournal.net/text.asp?2010/6/3/382/73352



 > Introduction Top


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 Top


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.
Figure 1: An 87-years-old female patient with MCC of the forehead

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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].
Figure 2: Octreoscan showing a highly significant uptake in the frontal and cervical regions as well as a focus at the right pulmonary apex

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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.
Figure 3: Clinically all perceptible frontal and cervical lesions had completely disappeared after two months of treatment

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Figure 4: Octreoscan 10 weeks after the treatment showing the complete disappearance of the frontal and cervical uptake

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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 Top


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 Top

1.Gupta S, Wang L, Nghiem P. Merkel cell carcinoma: Information for patients and their physicians.  Back to cited text no. 1
    
2.Hodgson NC. Merkel Cell Carcinoma: changing incidence trends. J Surg Oncol 2005;89:1-4.  Back to cited text no. 2
[PUBMED]  [FULLTEXT]  
3.Heath M, Jaimes N, Lemos B, Mostaghimi A, Wang LC, Peρas PF, Clinical Characteristics of Merkel Cell Carcinoma at Diagnosis in 195 patients: the AEIOU featuers. J Am Acad Dermatol 2008;58:375-81.  Back to cited text no. 3
    
4.Medina-franco H, Urist MM, Fiveash J, Heslin MJ, Bland KI, Beenkeu SW. Multimodality treatment of Merkel Cell Carcinoma: case series and literature review of 1024 cases. Ann Surg Oncol 2001;8:204-8.  Back to cited text no. 4
    
5.Garneski KM, Nghiem P. Merkel Cell Carcinoma Adjuvant therapy: Current data support Radiation but not Chemotherapy. J Am Acad Dermatol 2007;57:166-9.  Back to cited text no. 5
[PUBMED]  [FULLTEXT]  
6.Thomas F, Parmar H, Prevost G, Kuhn JM, Bejot JL, Moreau JP. Somatostatin analogs in oncology. Bull Cancer 1991;78:693-707.  Back to cited text no. 6
    
7.Lamberts SWJ, Reubi JC, Krenning EP. The role of somatostatin analogs in the control of tumor growth. Semin Oncol 1994;21:61-4.  Back to cited text no. 7
    
8.Lamberts SW, Van der Lely AJ, de Herder WW, Hofland LJ. Octreotide. N Engl J Med 1996;334:246-54.   Back to cited text no. 8
[PUBMED]  [FULLTEXT]  
9.Hofland LJ, van Koetsveld PM, Wouters N, Waaijers M, Reubi JC, Lamberts SW. Dissociation of antiproliferative and antihormonal effects of the somatostatin analog octreotide on 7315b pituitary tumor cells. Endocrinology 1992;131:571-7.  Back to cited text no. 9
[PUBMED]  [FULLTEXT]  
10.Inoue T, Yoneda K, Manabe M, Demitsu T. Spontaneous regression of merkel cell carcinoma: a comparative study of TUNEL index and tumor-infiltrating lymphocytes between spontaneous regression and non-regression group. J Dermatol Sci 2000;24:203-11.  Back to cited text no. 10
[PUBMED]  [FULLTEXT]  
11.Cirillo F, Filippini L, Lima GF, Caresana G, Alquati P. Merkel cell tumor. Report of case and treatment with octreotide . Minerva Chir 1997;52:1359-65.  Back to cited text no. 11
[PUBMED]    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

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