DREXEL UNIVERSITY

Merkel Cell Carcinoma

BMES 502

Medical Sciences – II

Ankita Mishra am592@drexel.edu 11466208

Uday Kiran T udaykrian@drexel.edu 11486932

Date of Submission

14th

March 2008

Department of Biomedical Engineering, Science and Health Systems

Drexel University Winter 2008

2

Abstract

Merkel cell carcinoma or more commonly known as MCC is a type of skin cancer.

Though it is rare type of cancer, it is highly malignant, aggressive in nature and

holds a high mortality rate. Moreover over decades there has been a fair increase in

the number of people suffering from this cancer. Its affect on whites, elderly

people and immunosuppressant is more comparatively. Also exposure to sun can

be another factor for its occurrence. Biopsy, surgery, and radiation etc are different

modalities that can be used for its diagnosis in most cases. Imaging modalities like

computed tomography, magnetic resonance, positron emission tomography can be

used for its detection. Management of the disease is very challenging. For the

means of treatment over-`aggressive surgery should be avoided. Adjuvant radiation

therapy often turns out to be highly effective in case of MCC. Also adjuvant

chemotherapy can be used but it holds high morbidity and there are not much

proven benefits with the application. The most optimum approach suggests a

multidisciplinary coordination between dermatologists, surgeons, radiation, and

medical oncologists for its treatment.

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TABLE OF CO�TE�TS

S �o. Title Page �o.

Title Page 1

Abstract 2

Table of Contents 3

List of Illustrations 4

I. Introduction – What is MCC? 5

II. Epidemiology 6

III. Etiology and Pathogenesis 7

IV. Different Stages of MCC 9

V. Causes 9

VI. Diagnosis 11

VII. Treatment 12

VIII. State-of-art 14

IX. Discussion 15

References 17

4

List of Illustrations

FIGURES Figure �o. Title Page �o.

Figure. 1(a) Merkel cells are located in the basal layer of the epidermis 5

Figure. 1(b) Immunostain by CK20 shows characteristic paranuclear dot stain

pattern in Merkel cell carcinoma

5

Figure. 2 (a) MCC frequently has a "cyst-like" appearance. 5

Figure. 2 (b) MCC on the knee of a 70-year-old woman with chronic

lymphocytic leukemia.

8

Figure. 2 (c) MCC on the ear of an 87-year-old woman. The lesion grew rapidly

and was non-tender.

8

TABLES

Figure �o. Title Page �o.

Table 1 Clinical Features of MCC 7

Table 2 Scope of different stages of MCC 9

Table 3 Treatment of different stages 14

Table 4 Summary of roles of Treatment 16

Table 5 Suggestion of management for MCC 16

5

Introduction

Merkel-cell carcinoma (MCC) is a form of skin cancer which is rare to be found and is of

neuroendocrine nature. It is aggressive type of cutaneous malignancy and has high mortality rate.

The cell of origin is thought to be the Merkel cell or skin-pressure receptor. MCC has been

described not lately compared to merkel cell which was described more than 100 years ago. It

was in 1875 that Friedrich S. Merkel (1845–1919) first described human merkel cells. Since

these cells were associated with nerves he named these cells Tastzellen (touch cells) assuming

that they had a sensory touch function within the skin. These cells are believed to be slow-acting

mechanoreceptors in the basal layer of the epidermis that provide information about touch and

hair movement.[1][2]

The cells are of neuroendocrine origin and migrate from the neural crest to

the skin, where they differentiate into mature Merkel cells and express several neuronal and

epithelial markers.[3]

Figure 1: (a) Merkel cells are located in the basal layer of the epidermis. © Medical Art Service,

Munich/Wellcome Medical Library (on the left) (b) Immunostain by CK20 shows characteristic

paranuclear dot stain pattern in Merkel cell carcinoma (on the right)

It was in 1972 that five cases of "trabecular cell carcinoma of the skin" were described by Toker.

Later in 1980 the tumor was given the name MCC. Prior to 1992 electron microscopy was

essentially used for the diagnosis of the cancer. Since then antibodies to cytokeratin-20 are more

readily used for the diagnosis purpose as they are more specific and relatively easier way of

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diagnosing. More recently in 2004 an elegant transgenic mouse model was used to isolate normal

merkel cells from mouse skin and it was found that they possessed excitable calcium channels

and were capable of neurotransmitter release, suggesting that they do indeed play a role in touch

sensation within the skin.[2]

Epidemiology

MCC is an uncommon form of cutaneous malignant disease. Recent studies have indicated that

the number of MCC cases within the United States is between 600 and 1000 cases per year

depending on the particular tumor registry analyzed.[4][5]

This cancer is far more common in

whites than in blacks, consistent with a known role for ultraviolet radiation in the pathogenesis.

Specifically, the rates in whites have been reported as 0.23 per 100,000 as compared to 0.01 per

100,000 for blacks. [6] Although not specifically reported, rates in Hispanics and Asians are likely

intermediate between those in blacks and whites. MCC tends to be more common in men than in

women (2:1 in ratio). [4]

The elderly people are more prone to the disease. Incidences of the disease are increasing with

each passing year. There are two factors most likely which can explain this increase. One being

the accurate diagnosis of this malignancy through the routine use of cytokeratin-20

immunohistochemistry and the improved recognition of this malignancy by

dermatopathologists.[1]

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Clinical Features of Merkel Cell Carcinoma

� Firm; red, purple, or skin-colored, nontender papule or nodule

� Most lesions are < 20 mm in diameter at diagnosis

� Rapid growth within 1–3 mo

� Usually on a sun-exposed location (but not always)

� Ulceration is rare

� Locally aggressive, with local discontinuous and distant lymphatic spread

Table 1 Clinical features of MCC. Copyright © The McGraw-Hill Companies. All rights reserved.

Etiology and Pathogenesis

Age Greater Than 65 Years

The median age for diagnosis of MCC is 70 years. It is rarely found in children. For age less than

50 years the chances for MCC are about 5 percent. Increase in the incidence of disease is more

after age of 70 as compared with age less than 60 years. [7]

Sun Exposure

MCC can be caused due to exposure to sunlight, prolonged ultraviolet exposure, and

photochemotherapy. Though sun is not required for MCC development, the vast majority of

MCC are present on skin exposed to sun. It further depends on the body regions which are

exposed to sun and also on the geographical distribution and conditions. However presence of

tumors in area not exposed to sunlight suggest other factors as well responsible for the cause.

The tumour has also been documented in patients with congenital ectodermal dysplasia,

Cowden's disease, and Hodgkin's disease.[1][3]

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Immune Suppression

Another factor associated with MCC is immunosuppression. Several of the drugs used to

suppress the immune system in transplant recipients have previously been shown to act directly

on certain tumor cells to augment their growth and aggressive behavior.[1] MCC has also been

reported in patients with HIV infection and with chronic lymphatic leukaemia, suggesting that

these diseases have a role in the pathogenesis of MCC. The relative risk of developing MCC in

individuals with acquired immunodeficiency has been calculated to be 13·4 [1] [3]

Molecular Genetics

Nothing much is known about MCC at the molecular level. It shares histologic features with

another neuroendocrine carcinoma, small cell lung cancer, but if these similarities at the

histologic level extend to the genetic level is still not clear. So far there is no clear tumor

suppressor gene or oncogene that has been conclusively implicated in MCC. [1]

Figure 2.Clinical appearance of Merkel cell carcinoma (MCC). A. MCC frequently has a "cyst-

like" appearance. This is reflected in the differential diagnoses given by clinicians at the time of

the biopsy, with cyst/acneiform lesion being the most common clinical impression. B. MCC on

the knee of a 70-year-old woman with chronic lymphocytic leukemia. For 6 months this lesion

was thought to be a "cyst"; consequently, diagnosis and treatment were delayed. Pen marks

indicate palpable satellite metastases that developed several months after the primary lesion,

presumably tracking via lymphatics. C. MCC on the ear of an 87-year-old woman. The lesion

grew rapidly and was non-tender. After approximately 3 months, it was biopsied by a clinician

who listed squamous cell carcinoma as the presumptive diagnosis. [1]

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Different Stages of Merkel Cell Carcinoma:

Based on the clinical presentations and data available different therapeutic regimes can be

defined for MCC. This gives a classification for different stages into which the patients can be

categorized. [8]

The different stages are:

Stage Scope

Stage I The primary tumor does not spread to lymph node or any other part of

the body. Lymph nodes hold the protective functionality and help in

fighting infections and diseases. These have cells which fight infection.

Stage II The cancer spreads to nearby lymph nodes but other parts of the body

remain unaffected.

Stage III The cancer spreads not only to the nearby lymph nodes but also other

parts of the body

Recurrent

Stage

This is another stage where the cancer recurs after being treated once. It

might affect the same part or some other part than the previous

occurrence.

Table 1. Scope of different stages of MCC

Causes:

• MCC is most likely to occur in the regions of body exposed to sun, head, neck and face.

This made scientists to observe the exposure to sunlight, UV-B rays, has an effect on the

Merkel cells. UV Index provides a forecast of the expected risk of overexposure to the

sun. When UV index is over 9, UV-B radiations are extremely strong, stated by WHO.

Of all the UV rays, UVB rays have the strength to penetrate through the epidermis. UVB

rays simulate the melanocytes to produce melanin, which appears as a 'sun-tan' on the

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skin and these rays can also alter DNA causing cancers. This is one of the causes for

MCC, as well as Basal cell carcinoma (BCC). The UVB rays promote tumor progression

by the destruction of tumor suppressor genes including p53 and also disturb the gene

expressions of chemokines, pro-inflammatory mediators, and DNA repair enzymes. [12]

PUVA (Psolaren UVA) treatment of psoriasis, eczema, uses UV radiation exposure for

curing. However, overexposure of UV radiation has adverse effects causing skin cancers.

• The risk of MCC in renal transplantation has been estimated at 0·13 per 1000 person-

years at risk, which is substantially lower than the risk of small-cell carcinoma in this

patient population. [9] HIV is very known disease which is associated with malfunctioning

of the human immune system.[13]

It gives chances for many cancers and neoplastic

disorders to proliferate. Studies have evaluated increasing risk for cell carcinomas in skin

due to weakened cellular immune system. In the past prior to immunohistochemistry, due

to lack of knowledge about the disease MCC has been wrongly diagnosed as lymphoma,

melanoma, or undifferentiated carcinoma.

• To prevent the body from rejecting the organ transplant, bone marrow transplant or

treating auto-immune diseases (rheumatoid arthritis, Crohn's disease),

immunosuppressive drugs, like cyclosporine, are used. This makes the body vulnerable to

infections, diseases and also cancers.[30]

• Polyomavirus, a virus which causes neuroectodermal skin disease in immunosuppressed

people, has an indirect path causing merkel cell carcinoma. 'Polyoma' refers to virus's

ability to multiple (poly-) tumors (-oma-). JC (John Cunningham), BK, KI (Karolinska

Institute), WU (Washington University) viruses are four types of polyomaviruses found

in humans. Polyomaviruses[14]

in human, with genomes BKPyV, JCPyV, KIPyV,

WUPyV etc., infects the urinary tract, nephropathy, leukoencephalopathy in

immunosuppressed patients. Experiments conducted by Feng et al. (transcriptome

subtraction) found that there is correlation between the gene expressions of the tumor and

polyomavirus T- antigen like sequence and tyrosine phosphotase (human receptor). This

polyomavirus is named as Merkel cell polyomavirus (MCV).

• Embryonic lethal abnormal vision (ELAV) like-binding proteins, a shuttling protein

between nucleus and cytoplasm, are responsible for mRNA stability of eukaryotic gene

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expression in all neurons after birth which neutralizes mRNA containing adenine and

uridine rich elements. HuR[15]

, a member of the Eval/Hu family of the m-RNA binding-

protiens, staining patterns were observed in MCC tumors samples. A subset of MCC

tumors and many lymph node metastases were found to have cytoplasmic HuR gene

expression. The HuR characteristic of carcinogenesis caused the MCC tumor progression.

• Inorganic Arsenic (As) can cause various cutaneous problems like Bowen's disease.

People suffering from Bowen's disease, a neoplastic skin disease considered as a

squamous cell carcinoma (SCC) was found to have signs of MCC when the tumor was

examined histopathologically. The carcinogenic characteristic of inorganic arsenic arises

from its property of sister chromatid exchange and oxygen radicals, and stimulates cell

proliferation and DNA damage[16]

. Dermatopathalogical examinations reported existence

of a basal membrane which seperates epidural to dural membranes and there was no

apparent relationship between Bowen's disease and MCC. Atypical tumor cells formed a

trabecular pattern in dermal layer which correspond to same patterns of MCC. Images

from electron microscope have showed presence of dense core granules which is a sign

for MCC.

Diagnosis:

Octreotide scan: Octreotide is an octreotide whose structure is similar to natural somatostatin. It

inhibits secretion of many hormones like gastrin, glucagon, growth hormone, insulin, secretin,

TSH and other neuroendrocrine derived cancers. This scan is often used for detection of

carcinoid and other tumor types. For this a drug, radioactive octreotide is injected in the vein

which travels through the bloodstream. The radioactive octreotide attached to the tumor cells

which can then be detected using a device and pictures can be taken of the region where the

tumor lies. This method can be used for the detection of metastatic tumor localization. [10]

Immunohistochemistry: It is a process by which the antigens and proteins are localized in tissue

cells by the antigen-antibody interaction where labeled antibodies are used as specific reagents.

The diagnosis of MCC can be challenging the immunohistochemical profile is important in

confirming the microscopic diagnosis. [11]

MCC can be diagnosed by observing the cytokeratin

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(CK) 20, CK7, epithelial membrane antigen, and neuron-specific enolase via

immunohistochemical profile besides microscopic images.[17]

Sentinel lymph node biopsy: Removal of tumor tissues from body for diagnosis and staging of

the cancer is called as biopsy. The sentinel lymph node, which the primary site for the spreading

of the cancer, is examined for the staging of the cancer. Upon the injection of the radioactive

substance, the lymph nodes are stained and can be removed for microscopic examinations.

Computed Tomography: Contrast-enhanced CT images can distinguish skin lesions and lymph

nodes from other tissues based on density. Nodal and subcutaneous fat metastases are slightly

hyperdense than the liver, mediastenum, periostenum, lung and adrenal gland detected. [18]

Positron Emission Tomography: The uptake of FDG is high in the regions of brain, kidney and

cancer cells, where the release of glucose is prevented by phosphorylation. Fluorine-18-

fluorodeoxyglucose positron emission tomography (FDG PET) imaging has been beneficial in

directing management and predicting clinical course of MCC. FDG PET imaging is a very

sensitive modality in staging, assessment of treatment response, and surveillance of MCC. [26]

Treatment of Different Stages:

Stage I Disease

The main aim of the treatment of disease is to control its growth in the site of origin or the

primary site and the lymph nodes as any uncontrolled growth of the disease can increase the risk

of its spread to distant area, complicating the situation and affecting the quality of life for the

patient.[31]

Treatment for disease that remains localized to the primary site, surgery and radiation can be

used. Surgical excision of the primary tumor with a margin of 2 to 3 cm is the treatment choice.

[9] This range is based on the tumor's propensity to spread via the dermal lymphatics. For the use

of radiation as a mode of treatment, having an adequate margin for surgery becomes less

important. Moreover if surgery is only to be used, for smaller margins the relapse rates will be

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high. [3]

Postoperative radiotherapy has been recommended by authors based on comparison of

treatment with surgery alone and that being followed by postoperative radiotherapy. Due to the

addition of postoperative radiotherapy there is a decrease in the local failure from 39% to 26%

and the regional failure from 46% to 22%. [3]

Because of the tendency of tumor for rapid

repopulation after surgery, radiation should be started as soon as the wounds have healed

adequately. Radiation volumes have included the primary site with generous margins of 3–5 cm

to ensure that the dermal lymphatics surrounding the primary are treated to full dose. With the

use of radiation alone durable results of local control can be achieved. This shows that the

tumour has inherent radiosensitive. Higher doses are used in treating MCC with areas of bulky

disease. Mohs micrographic surgery can be recommended for tumors located in the face. Also in

case the primary tumor is inoperable or the patient is poor surgical candidate radiotherapy can be

used alone. The place of chemotherapy (a process where the disease is treated chemically killing

the cancerous cells) for stage I disease remains unknown. More data has to be acquired before it

can be recommended as standard treatment. [3]

Stage II disease

Management principles for the primary site are the same as for stage I disease. Probability of

developing distant disease is high for patients which have extensive nodal disease. Nodal masses

are commonly bulky and multiple. Along with the resection of the primary disease nodal

dissections can be done. However operation on nodes requires a careful consideration and

following factors need to be considered before proceeding: the operability of the nodal mass, the

patient's general condition, and the site of the involved nodes. Radiation can be used as definitive

treatment for the nodal mass and large masses can be sterilized with radiation doses. The use of

adjuvant chemotherapy can also be considered especially for patients with high-risk disease.

Chemotherapy can be given as a radiation sensitizer to improve locoregional control.[29]

Stage III disease

In general, disseminated diseases carry very poor prognosis and the median survival of patients

having distant metastases is only 9 months. Distant sites of metastatic disease are common and

occur in 28–70% of cases. The organs most commonly affected are the liver, bone, lung, brain,

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and skin. Responses to chemotherapy are usually short-lived, and most patients ultimately die

from the disease. Radiation can be used to palliate bony and brain secondary tumors, and to offer

palliation with advanced cutaneous deposits that are bleeding or fungating. Because the tumour

is sensitive, radiation can usually be given in about five fractions, although bone pain is relieved

well in a single fraction. No prospective chemotherapy trials have been done in MCC, nor have

any randomized trials to compare different chemotherapeutic regimens. Hence, the effect of

chemotherapy on survival and quality of life has not been determined.

Stage Treatment

Stage I Wide local excision, radiotherapy, and/or lymphadenectomy

Stage II Surgery, radiotherapy, chemotherapy

Stage III Chemotherapy, cytokines

Table 2. Treatment of different stages

State-of-Art

� MCC usually occurs in elderly patients (age 70+ years) and very unlikely to be found in

young people (<5% in 0-50 years). Recently, some cases of MCC have shown

reactivity for chromogranin, synaptophysin, vasoactive intestinal peptide, pancreatic

polypeptide, calcitonin, substance P, somatostatin, ACTH, other peptide hormones

and CD117.[19]

� Platelet-derived growth factor receptor alpha (PDGFRA), a gene similar to a subset of

gastrointestinal stromal cell tumors, was also responsible for MCC in few cases. The base

change in the exons of PDGFRA was observed in three of nine MCC cases, using

immunohistochemistry. Imatinib therapy (inhibition of tyrosine kinase enzymes using

drugs, mesylate salt) can be used for this type of MCC as the mutation may be

oncogenic.[20]

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� A report from Naval Medical center, CA stated that multiple cutaneous lesions developed

either in the local region or at distant sites during the course of the MCC disease, along

with micrometastatses to the sentinel lymph node. Synchronous onset of multiple

cutaneous neuroendocrine (Merkel cell) carcinomas is localized to the scalp.[21]

� Carcinoids are neuroendocrine tumors commonly found in the gastrointestinal and

bronchopulmonary tracts, which can also cause skin cancer through metastasizing lymph

nodes.[22]

� Several new antigens and proteins are used to differentiate various carcinomas. A recent

study discovered that SOX9 transcription factor is expressed in the outer layer of the

epithelial sheath, and the hair stem cells (hair follicles). It is one of the factors responsible

for skin cancers activating Sonic hedgehog (Shh) pathway. SOX9 feature is used to

distinguish MCC from BCC. [23]

S100A6, a calcium binding protein in the S100 family,

is present in neural tumors, fibrohistiocytic tumors and melanomas. BCC and MCC gave

a negative result whereas several SCC samples expressed S100A6 (staining). [24]

Mast

cells are used for prognosis of MCC with respect to lymphovascular invasion and tumor

size. [25]

Immunohistochemical assays were used to count the number of mast cells which

are significantly more.

Discussion

Based on the knowledge so far, it can be concluded that MCC is a very rare and aggressive

neuroendocrine tumor of the skin. It is a highly malignant tumor which shows tendency for local

recurrence, nodal spread and distant spread. [28]

As stated, it can be seen that natural history of

MCC is variable and depends on the stage of disease at the time when it is present. The best way

to manage MCC would be through multidisciplinary management. Patients with MCC can be

optimally managed, through surgery of primary tumor, with adequate margins and post-operative

radiotherapy to control local and regional disease. All the patients suffering from primary tumor

should be treated with conservative surgery followed by radiotherapy. [1][7]

The role of adjuvant

chemotherapy at this stage is still under the process of being defined. For patients who are

suffering with respectable nodal disease should be treated with regional node dissection which

16

should then be followed by post-operative radiotherapy. For the patients suffering with fixed and

unrespectable nodal form should get treated with pre-operative chemotherapy and radiotherapy

and that should be followed by a nodal dissection. Since MCC has the proclivity for

hematogenous metastases and its responses to chemotherapy are high, adjuvant chemotherapy

should be considered as a part of the initial treatment. Inspite of the fact that the size of these

tumors is relatively small there is a need for insistent therapy. Half way treatment does not find

any scope for MCC treatment. [7]

Definite Role Possible Role �o Role

Surgery 1. Excisional Biopsy 1. Nodal dissection for

positive nodes

1. Node dissection

for nodes > 6cm

2. Biopsy of nodes in patients

with unknown primary

2. Sentinel node biopsy,

especially for midline

lesions

2. Prophylactic

node dissection

Radiotherapy 1. Postoperatively for clear

margins and positive

margins.

1. Alone for small lesions

2. Alone for the areas difficult

to operate on

2. Alone for involved nodes

3. Alone for medically unfit or

inoperable disease.

Chemotherapy 1. Palliation of metastatic

disease

1. As a radiation sensitizer 1. As sole

Adjuvant

therapy

2. Limb perfusion

Table 3. Summary of the roles of treatment. Source: Penn I, First MR: Merkel's cell carcinoma in organ

recipients: report of 41 cases. Transplantation

Summary of suggested management for Merkel cell carcinoma

History and Physical examination

• Careful Examination for satellite lesions, nodes and distant disease

Investigations

• Computed Tomography scan of the chest and abdomen: bone scan if there is bone pain or elevated serum

alkaline phosphatase.

Local disease

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• Excision biopsy of the primary

• Postoperative radiotherapy to the primary site and draining nodes to a dose of 45-50 Gy in 25 fractions.

Loco-regional disease

• Excision biopsy of the primary.

• Involved nodes < 6cm can be dissected or can be treated with radiation alone (60 GY).

• Postoperative radiotherapy (50 GY) to the primary.

• �odes > 6 cm should be treated with radiotherapy with or without chemotherapy.

Metastatic Disease

• Patients with metastatic disease should be considered for palliative chemotherapy.

Table 4 Summary of suggested management. Source: Penn I, First MR: Merkel's cell carcinoma in organ

recipients: report of 41 cases. Transplantation

References:

[1] Merkel Cell Carcinoma; Paul Nghiem, Natalia Jaimes.

[2] Haeberle H et al: Molecular profiling reveals synaptic release machinery in Merkel cells.

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[3] Merkel-cell carcinoma of the skin The Lancet Oncology - Volume 5, Issue 10 (October

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[4] Agelli M, Clegg LX: Epidemiology of primary Merkel cell carcinoma in the United States. J

Am Acad Dermatol 49:832, 2003.

[5] Pan D, Narayan D, Ariyan S: Merkel cell carcinoma: five case reports using sentinel lymph

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[6] Miller RW, Rabkin CS: Merkel cell carcinoma and melanoma: etiological similarities and

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[7] Penn I, First MR: Merkel's cell carcinoma in organ recipients: report of 41 cases.

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[8] P J Allen, Z F Zhang, and D G Coit Surgical management of Merkel cell carcinoma; Ann

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[9] Atlas of Cancer of the Skin Edited by Gunter Burg, MD

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[10] Kwekkeboom DJ, Hoff AM, Lamberts SW, Oei HY, Krenning EP. Somatostatin

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[11] Calder KB, Coplowitz S, Schlauder S, Morgan MB. A case series and immunophenotypic

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[15] Expression of HuR in Merkel cell carcinoma and in normal skin; Virve Koljonen1, Tom

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[16] Merkel cell carcinoma, Bowen’s disease and chronic occupational arsenic poisoning;

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[21] Synchronous onset of multiple cutaneous neuroendocrine (Merkel cell) carcinomas

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[22] Raffaella Santi, Daniela Massi, Francesca Mazzoni, Lorenzo Antonuzzo, Camilla E.

Comin (2008) Skin metastasis from typical carcinoid tumor of the lung

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[23] Valérie P.I. Vidal, Nicolas Ortonne, Andreas Schedl (2008); SOX9 expression is a

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[24] Douglas R. Fullen, Angela J. Garrisi, Donita Sanders, Dafydd Thomas (2008)

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[25] Mast cells have prognostic value in Merkel cell carcinoma. - Beer TW - Am J

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[26] Merkel Cell Carcinoma: Is there a Role for 2-Deoxy-2-[F-18]fluoro-D-glucose–Positron

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S. Gambhir; Mol Imaging Biol (2006) 8:212Y217.

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[28] Poulson M. Merkel-cell carcinoma of the skin. Lancet Oncol 2004; 5:593–9

[29] Al-Ghazal SK, Arora DS, Simpson RH, et al. Merkel cell carcinoma of the skin. Br J

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combined surgery and radiation therapy. Am Surg 1986; 52:159–64.

[30] Buell JF, Trofe J, Hanaway MJ, et al. Immunosuppression and Merkel cell cancer.

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[31] Haag M, Glass LF, Fenske NA. Merkel cell carcinoma: diagnosis and treatment.

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