Merkel Cell Cancer

Understanding the Lymph System

2009-10-28T08:21:00.000-07:00

Understanding the Lymph System

I thought it would be helpful for readers to understand the lymph system, the anatomy, what it does, and how it helps with immunity.

Listed below are information pages that should be quite helpful and each page has many additional links for more a more in depth study.

Anatomy of the Lymph System

Lymphatic System Functions

Lymphatic System and Immunity

Pathology of the Lymph Nodes and Lymphoma

Lymph Nodes

Lymph Fluid

Arm and Leg Swelling After Merkel Cell Cancer

2009-10-17T07:14:00.000-07:00

Arm and Leg Swelling After Merkel Cell Cancer

With the advent of better and more effective cancer treatments, the survival rate for all cancers has risen dramatically. With this progress, a new and often misunderstood and misdiagnosed complication has arisen.

Many cancer survivors , having overcome cancer, find themselves with sudden and often unexplained swelling, usually of the arms or of the legs.

This swelling occurs because of one of several factors.

First, the swelling begins after lymph nodes have been removed for cancer biopsies.

Second, the swelling may start as a result of radiation damage to either the lymph nodes and/or the lymph system.

Due to either the removal of lymph nodes or damage to the lymph system, your body is no longer able to rid itself of excess fluids. The fluids collect in the limbs effected and swelling begins.

This swelling is called lymphedema and it can effect either your leg or your arm. The swelling that occurs is permanent, and while it is not curable it is treatable.

Hopefully, in the future with radiological scans becoming more sensitive and with increased use of such techniques such as the small needle biopsy, we can put an end to this epidemic of secondary lymphedema from cancer biopsy.

Permanent Leg or Arm Swelling

In the situation of any permanent leg swelling whether the cause is known or unknown, the diagnoses of lymphedema must be considered

There are several groups of people who experience leg or arm swelling from known causes, but it doesn't go away or unknown causes where the swelling can actually get worse as time goes by.

Group One

This group includes those who have had the injuries, infections, insect bites, trauma to the leg, surgeries or reaction to a medication. When this swelling does not go away, and becomes permanent it is called secondary lymphedema.

Group Two

Another extremely large group that experiences permanent leg or arm swelling are cancer patients, people who are morbidly obese, or those with the condition called lepedema. What causes the swelling to remain permanent is that the lymph system has been so damaged that it can no longer operate normally in removing the body's waste fluid.

In cancer patients this is the result of either removal of the lymph nodes for cancer biopsy, radiation damage to the lymph system, or damage from tumor/cancer surgeries.

This is also referred to as secondary lymphedema.

Group Three

Group three consists of people who have leg or arm swelling from seemingly unknown reasons. There may be no injury, no cancer, no trauma, but for some reason the leg simply is swollen all the time.

The swelling may start at birth, it may begin at puberty, or may begin in the 3rd, 4th or even 5th decade of life or sometimes later.

This type of leg or arm swelling is called primary lymphedema. It can be caused by a genetic defect, malformation or damage to the lymph system while in the womb or at birth or be part of another birth condition that also effects the lymph system.

This is an extremely serious medical condition that must be diagnosed early, and treated quickly so as to avoid painful, debilitating and even life threatening complications. Treatment should NOT include the use of diuretics.

WHAT IS LYMPHEDEMA?

Lymphedema is defined simply as an accumulation of excessive protein rich fluid in the tissues of the leg. The accumulation of fluid causes the permanent swelling caused by a defective lymph system.

A conservative estimate is that there may be 1-2 million people in the United States with some form of primary lymphedema and two to three million with secondary lymphedema.

WHAT ARE THE SYMPTOMS OF LYMPHEDEMA?

If you are an at risk person for arm lymphedema there are early warning signs you should be aware of. If you experience any or several of these symptoms, you should immediately make your physician aware of them.

1.) Unexplained aching, hurting or pain in the arm or leg

2.) Experiencing “fleeting lymphedema.” This is where the limb may swell, even slightly, then return to normal. This may be a precursor to full blown arm lymphedema or leg lymphedema.

3.) Localized swelling of any area. Sometimes lymphedema may start as swelling in one area, for example the hand, or between the elbow and hand. This is an indication of early lymphatic malfunction.

4.) Any arm inflammation, redness or infection.

5.) You may experience a feeling of tightness, heaviness or weakness of the arm.

The symptoms for leg lymphedema are very similar to ones for the arm.

HOW IS LYMPHEDEMA TREATED?

The preferred treatment today is decongestive therapy. The forms of therapy are complete decongestive therapy (CDT) or manual decongestive therapy (MLD), there are variances, but most involve these two type of treatment.

It is a form of massage therapy where the leg is very gently massaged to actually move the fluid out of the leg and into an area where the lymph system still functions normally.

With these massage treatments, swelling is reduced and then the patient is fitted with a pre-measured custom pressure garment to keep the swelling down and/or is taught to use compression wraps to maintain the leg size.

WHAT ARE SOME OF THE COMPLICATIONS OF LYMPHEDEMA?

1. Infections such as cellulitis, lymphangitis, erysipelas. This is due not only to the large accumulation of fluid, but it is well documented that lymphodemous limbs are localized immunocompromised.

2. Draining wounds that leak lymphorrhea which is very caustic to surrounding skin tissue and acts as a port of entry for infections.

3. Increased pain as a result of the compression of nerves usually caused by the development of fibrosis and increased build up of fluids.

4. Loss of Function due to the swelling and limb changes.

5. Depression - Psychological coping as a result of the disfigurement and debilitating effect of lymphedema.

6. Deep venous thrombosis again as a result of the pressure of the swelling and fibrosis against the vascular system. Also, can happen as a result of cellulitis, lymphangitis and infections.

7. Sepsis, Gangrene are possibilities as a result of the infections.

8. Possible amputation of the limb.

9. Pleural effusions may result if the lymphatics in the abdomen or chest are to overwhelmed to clear the lung cavity of fluids.

10. Skin complications such as splitting, plaques, susceptibility to fungus and bacterial infections.

11. Chronic localized inflammations.

CAN LYMPHEDEMA BE CURED?

No, at the present time there is no cure for lymphedema. But it can be treated and managed and most of the complications can be avoided. Life with lymphedema can still be active and full, with proper treatment, patient education, and patient life style adaptation.

For extensive information on lymphedema, please visit our home page:

Lymphedema People

Detection of Merkel cell polyomavirus in Merkel cell carcinoma and Kaposi's sarcoma.

2009-10-11T05:42:00.000-07:00

Detection of Merkel cell polyomavirus in Merkel cell carcinoma and Kaposi's sarcoma

J Med Virol. 2009 Nov

Katano H, Ito H, Suzuki Y, Nakamura T, Sato Y, Tsuji T, Matsuo K, Nakagawa H, Sata T.

Department of Pathology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku, Tokyo 162-8640, Japan.

email: Harutaka Katano (katano@nih.go.jp)

Merkel cell carcinoma is a rare malignancy that sometimes occurs in the skin of elderly people. Recently, a new human polyomavirus, Merkel cell polyomavirus (MCPyV) was identified in Merkel cell carcinoma. In the present study, MCPyV-DNA was detected in 6 of 11 (55%) cases of Merkel cell carcinoma by nested PCR and real-time PCR. Histologically, MCPyV-positive cases showed round and vesicular nuclei with a fine granular chromatin and small nucleoli, whereas MCPyV-negative cases showed polygonal nuclei with diffusely distributed chromatin. Real-time PCR analysis to detect the MCPyV gene revealed that viral copy numbers ranged 0.04-0.43 per cell in cases of Merkel cell carcinoma. MCPyV was also detected in 3 of 49 (6.1%) cases of Kaposi's sarcoma (KS), but not in 192 DNA samples of other diseases including 142 autopsy samples from 20 immunodeficient patients. The MCPyV copy number in KS was lower than that in Merkel cell carcinoma. PCR successfully amplified a full-length MCPyV genome from a case of KS. Sequence analysis revealed that the MCPyV isolated from KS had 98% homology to the previously reported MCPyV genomes. These data suggest that the prevalence of MCPyV is low in Japan, and is at least partly associated with the pathogenesis of Merkel cell carcinoma.

Wiley InterScience

Merkel Cell Originates From Skin, Not The Neural Crest

2009-10-11T05:36:00.000-07:00

Merkel Cell Originates From Skin, Not The Neural Crest

ScienceDaily (Oct. 7, 2009) — Case Western Reserve University School of Medicine assistant professor of pediatrics, neurosciences and otolaryngology, Stephen M. Maricich, M.D., Ph.D., and his team found that Merkel cells originate in the skin, not the neural crest lineage, as previously speculated.

The study, "Mammalian Merkel Cells are Descended from the Epidermal Lineage", was recently published in the online version of Developmental Biology and is slated its future print edition.

"Merkel cells," discovered by Friedrich Sigmund Merkel in 1875, are found in multiple regions of the skin and make contact with specialized never fibers, participating in the perception of touch.

"A real mystery surrounding Merkel cells was their developmental site of origin. Conflicting evidence suggested that these cells arose from either the skin or neural crest lineages, but there was no definitive proof of either origin," said lead author, Dr. Maricich.

Using genetically engineered mouse lines, the researchers were able to delete Atoh1, a gene essential to the formation of Merkel cells, from different areas of developing embryos. This "conditional deletion" of Atoh1 in the neural crest did not affect the Merkel cell population, however using this same technique in the skin lineage resulted in the loss of all Merkel cells.

"Knocking out Atoh1 in the neural crest line caused other problems for developing embryos, but Merkel cells were completely unaffected. However, loss of Atoh1 expression in the skin deleted all the Merkel cells," said Dr. Maricich. "This showed us that we had specifically targeted the Merkel cells and that Atoh1 expression by skin cells is necessary to their development."

The researchers also fate mapped the cells, a technique used to trace developmental fates of embryonic tissues. This analysis further supported their conditional knockout findings.

"The techniques used in this study will help neuroscientists to further explore the function of Merkel cells, including the behavioral consequences when only Merkel cells have been deleted," said Ellen Lumpkin, Ph.D., a study co-author and assistant professor of neuroscience, molecular physiology and biophysics and molecular and human genetics at the Baylor College of Medicine.

"It is thought that Merkel cells give rise to Merkel cell carcinoma, a rare but aggressive form of skin cancer that responds poorly to current treatments," said Dr. Maricich. "In addition to solving a 130 year-old mystery, our data may be relevant to the understanding of Merkel cell carcinoma, and may provide important clues in the search for novel therapeutic targets."

Funding for this study came from the National Institute of Neurological Disorders and Stroke and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Both are of the National Institutes of Health.

Adapted from materials provided by Case Western Reserve University, via EurekAlert!, a service of AAAS.

Science Daily

Merkel Cell Polyomavirus: A Specific Marker for Merkel Cell Carcinoma in Histologically Similar Tumors.

2009-10-11T05:32:00.000-07:00

Merkel Cell Polyomavirus: A Specific Marker for Merkel Cell Carcinoma in Histologically Similar Tumors.

Am J Surg Pathol. 2009 Oct 5

Duncavage EJ, Le BM, Wang D, Pfeifer JD.

Departments of *Pathology and Immunology daggerMolecular Microbiology, Division of Anatomic and Molecular Pathology, Washington University School of Medicine, St Louis, MO.

The recently described Merkel cell polyomavirus (MCPyV) is reportedly present in 50% to 80% of Merkel cell carcinomas (MCC). Although the virus has been shown to be absent from other cutaneous neoplasms, its association with malignancies that are histologically similar to MCC, specifically small cell carcinoma of the lung and other high-grade neuroendocrine tumors, has yet to be thoroughly investigated. To address this issue, we identified a set of 74 cases of visceral high-grade neuroendocrine tumors from a variety of anatomic sites, including 32 cases from the lung, 16 cases from the gastrointestinal tract, 20 cases from the female reproductive system, 3 cases from soft tissue, 2 cases from the head and neck region, and 1 case from the bladder. Using a set of primers optimized to detect MCPyV in formalin-fixed tissue, polymerase chain reaction (PCR)-based testing showed evidence of MCPyV DNA in only 1 of the 74 tumors; however, clinicopathologic review of the positive case (a neuroendocrine tumor of the small intestine) disclosed that the patient had a history of primary MCC of the buttock. PCR-based testing also showed no evidence of the related WU and KI polyomaviruses in the set of 74 cases. We conclude that, when evaluated by PCR-based testing, MCPyV is a specific marker for MCC that can be helpful in distinguishing cases of metastatic MCC from other high-grade neuroendocrine tumors. Our results also suggest that MCPyV does not have a role in the oncogenesis of visceral high-grade neuroendocrine tumors.

Lippincott, Williams & Wilkins

Association of Merkel Cell Polyomavirus-Specific Antibodies With Merkel Cell Carcinoma

2009-09-29T04:55:00.000-07:00

Association of Merkel Cell Polyomavirus-Specific

Antibodies With Merkel Cell Carcinoma

J Natl Cancer Inst. 2009 Sep 23

Carter JJ, Paulson KG, Wipf GC, Miranda D, Madeleine MM, Johnson LG, Lemos BD, Lee S,Warcola AH, Iyer JG, Nghiem P, Galloway DA.

Affiliations of authors: Program in Cancer Biology (JJC, GCW, DM, DAG), Division of Human Biology (JJC, MMM, LGJ, DAG), Division of Public Health Sciences (JJC, MMM, LGJ, DAG), and Division of Clinical Research (PN), Fred Hutchinson Cancer Research Center, Seattle, WA; Department of Microbiology (DAG), Department of Pathology (KGP, SL, PN), Department of Epidemiology (MMM), Department of Dermatology/Medicine (KGP, BDL, SL, AHW, JGI, PN), University of Washington, Seattle, WA.

Correspondence to: Denise A. Galloway, PhD, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, M.S. C1-105, Seattle, WA 98109-1024 (e-mail: dgallowa@fhcrc.org).

Background Merkel cell polyomavirus (MCPyV) has been detected in approximately 75% of patients with the rare skin cancer Merkel cell carcinoma. We investigated the prevalence of antibodies against MCPyV in the general population and the association between these antibodies and Merkel cell carcinoma. Methods Multiplex antibody-binding assays were used to assess levels of antibodies against polyomaviruses in plasma. MCPyV VP1 antibody levels were determined in plasma from 41 patients with Merkel cell carcinoma and 76 matched control subjects. MCPyV DNA was detected in tumor tissue specimens by quantitative polymerase chain reaction. Seroprevalence of polyomavirus-specific antibodies was determined in 451 control subjects. MCPyV strain-specific antibody recognition was investigated by replacing coding sequences from MCPyV strain 350 with those from MCPyV strain w162. Results We found that 36 (88%) of 41 patients with Merkel cell carcinoma carried antibodies against VP1 from MCPyV w162 compared with 40 (53%) of the 76 control subjects (odds ratio adjusted for age and sex = 6.6, 95% confidence interval [CI] = 2.3 to 18.8). MCPyV DNA was detectable in 24 (77%) of the 31 Merkel cell carcinoma tumors available, with 22 (92%) of these 24 patients also carrying antibodies against MCPyV. Among 451 control subjects from the general population, prevalence of antibodies against human polyomaviruses was 92% (95% CI = 89% to 94%) for BK virus, 45% (95% CI = 40% to 50%) for JC virus, 98% (95% CI = 96% to 99%) for WU polyomavirus, 90% (95% CI = 87% to 93%) for KI polyomavirus, and 59% (95% CI = 55% to 64%) for MCPyV. Few case patients had reactivity against MCPyV strain 350; however, indistinguishable reactivities were found with VP1 from strain 350 carrying a double mutation (residues 288 and 316) and VP1 from strain w162. Conclusion Infection with MCPyV is common in the general population. MCPyV, but not other human polyomaviruses, appears to be associated with Merkel cell carcinoma.

Journal National Cancer institute

Merkel cell carcinoma demographics, morphology, and survival based on 3870 cases: a population based study.

2009-09-21T21:57:00.000-07:00

Merkel cell carcinoma demographics, morphology, and survival based on 3870 cases: a population based study.
J Cutan Pathol. 2009 Jul 21

Albores-Saavedra J, Batich K, Chable-Montero F, Sagy N, Schwartz AM, Henson DE.
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City.

Correspondence to Jorge Albores-Saavedra, MD, Department of Pathology, Instituto Nacional de Ciencias Medicas y Nutricion, Vasco de Quiroga 15, Col. Seccion XVI, Salvador Zubiran, Mexico City Tlalpan, CP 14000, MexicoTel: + 52 55 548 70900Fax: + 52 55 548 53489e-mail:alboresjorge@yahoo.com

Background: Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine tumor arising predominantly on sun-exposed skin of older and usually immunosuppressed individuals.

Methods: Using data from NCI's SEER (Surveillance, Epidemiology, and End Results) Program from 1973 to 2006, we analyzed the demographics and survival of MCC.

Results: SEER had recorded 3870 cases of MCC. The incidence was higher in men (2380 cases, 61.5%) than in women (1490 cases, 38.5%). Most patients were White (94.9%) between 60 and 85 years of age. MCC was rare in Blacks. The most common location was the head and neck. The salivary glands, nasal cavity, lip, lymph nodes, vulva, vagina and esophagus were the most common extracutaneous sites. The 10-year relative survival rate was higher in women than men (64.8% vs. 50.5%, p <>

Conclusions: MCC arises predominantly in the skin of head and neck in White men above 70 years of age. Cases also occurred in extracutaneous sites. Age did not predict survival, yet gender, site and tumor size revealed clear differences. The most significant predictor of survival was tumor stage.

Wiley InterScience

Quantitation of human seroresponsiveness to Merkel cell polyomavirus.

2009-09-17T08:02:00.000-07:00

Quantitation of human seroresponsiveness to Merkel cell polyomavirus.
PLoS Pathog. 2009 Sep

Pastrana DV, Tolstov YL, Becker JC, Moore PS, Chang Y, Buck CB.
Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, Maryland, USA.

Merkel cell carcinoma (MCC) is a relatively uncommon but highly lethal form of skin cancer. A majority of MCC tumors carry DNA sequences derived from a newly identified virus called Merkel cell polyomavirus (MCV or MCPyV), a candidate etiologic agent underlying the development of MCC. To further investigate the role of MCV infection in the development of MCC, we developed a reporter vector-based neutralization assay to quantitate MCV-specific serum antibody responses in human subjects. Our results showed that 21 MCC patients whose tumors harbored MCV DNA all displayed vigorous MCV-specific antibody responses. Although 88% (42/48) of adult subjects without MCC were MCV seropositive, the geometric mean titer of the control group was 59-fold lower than the MCC patient group (p less then 0.0001). protein, Only 4% (2/48) of control subjects displayed neutralizing titers greater than the mean titer of the MCV-positive MCC patient population. MCC tumors were found not to express detectable amounts of MCV VP1 capsid protein, suggesting that the strong humoral responses observed in MCC patients were primed by an unusually immunogenic MCV infection, and not by viral antigen expressed by the MCC tumor itself. The occurrence of highly immunogenic MCV infection in MCC patients is unlikely to reflect a failure to control polyomavirus infections in general, as seroreactivity to BK polyomavirus was similar among MCC patients and control subjects. The results support the concept that MCV infection is a causative factor in the development of most cases of MCC. Although MCC tumorigenesis can evidently proceed in the face of effective MCV-specific antibody responses, a small pilot animal immunization study revealed that a candidate vaccine based on MCV virus-like particles (VLPs) elicits antibody responses that robustly neutralize MCV reporter vectors in vitro. This suggests that a VLP-based vaccine could be effective for preventing the initial establishment of MCV infection.

PubMed

The Interdisciplinary Treatment of Merkel Cell Carcinoma: A Retrospective Case Analysis and Review of the Current Literature.

2009-09-17T07:52:00.000-07:00

The Interdisciplinary Treatment of Merkel Cell Carcinoma: A Retrospective Case Analysis and Review of the Current Literature.
Zentralbl Chir. 2009 Sept

Strub B, Weindel S, Witt P, Grünert J.
Klinik für Hand-, Plastische und Wiederherstellungschirurgie Kantonsspital St. Gallen, Schweiz.

BACKGROUND: Merkel cell carcinoma is a rare, -aggressive, neuroendocrine malignancy of the skin. Over the period from June 2005 to January 2007 (18 months) 7 Merkel cell carcinomas in different tumour stages and localisations were -treated in our department for hand, plastic and reconstructive surgery. Given an incidence rate of approximately 0.1-0.4 per 100 000 habitants, this accumulation of cases is considerably higher than would be statistically expected. This led us to analyse our cases retrospectively and provided the opportunity to discuss the treatment modalities on the basis of the current literature.

PATIENTS AND METHODS: All patients were referred to our clinic after incomplete tumour excision and histopathological diagnosis elsewhere, for fur-ther surgical treatment. Two female and 5 male patients, aged 63 to 83 years, were treated. The patients' data were collected and analysed retrospectively.

RESULTS: In all cases an R0 resection could be achieved, with safety resection margins between 1.5 cm and 4.5 cm. The reconstruction of the resulting defects was achieved by skin transplants in six cases and a primary suture in one case. All patients received adjuvant radiotherapy. Furthermore, three patients received adjuvant chemotherapy due to metastases of the progressed Merkel cell carcinoma. Three patients remained free of recurrence and in two patients a progression of the tumour disease could be impeded, whilst two patients succumbed to their disease.

CONCLUSIONS: In the case of an early diagnosis, an R0 resection can usually be achieved. A safety -resection margin of a minimum of 1.5 cm in the face and 3 cm for localisation on the extremities should be obtained. To reduce the local recurrence rate, adjuvant radiotherapy should be conducted. The benefit from chemotherapy still -remains unclear. © Georg Thieme Verlag Stuttgart ˙ New York.

PubMed

Detection of Merkel cell polyomavirus DNA in Merkel cell carcinomas.

2009-06-08T07:34:00.000-07:00

Detection of Merkel cell polyomavirus DNA in Merkel cell carcinomas.

Br J Dermatol. 2009 May

Varga E, Kiss M, Szabó K, Kemény L.
Department of Dermatology and Allergology, University of Szeged, Korányi fasor 6, H-6720 Szeged, Hungary.

Background Merkel cell carcinoma (MCC) is a rare, aggressive tumour for which an increasing incidence has been reported. A new human polyomavirus, Merkel cell polyomavirus (MCV), was recently isolated from these tumours by applying digital transcriptome subtraction methodology. Objectives To detect the presence or absence of MCV in MCCs and other, randomly selected neoplasms. Methods Nine primary or recurrent MCCs from seven patients were examined; 29 other tumours (squamous cell, basal cell and basosquamous carcinomas and malignant melanomas) were examined for comparative purposes. Viral large T protein (LT1 and LT3), and viral capsid protein (VP1) were detected by primer-directed amplification, using a polymerase chain reaction (PCR)-based method, and the amplified PCR products were analysed by agarose gel electrophoresis and subsequent sequence analysis. Results The presence of viral T antigen and/or viral capsid DNA sequences was demonstrated in seven of the eight MCC lesions. None of the comparative samples contained MCV DNA. Conclusions Our findings strongly support the hypothesis that MCV infection may well be specific for MCC, and MCV may play a role in the pathogenesis of MCC.

WileyInterScience

Human Merkel cell polyomavirus infection I. MCV T antigen expression in Merkel cell carcinoma, lymphoid tissues and lymphoid tumors.

2009-06-08T07:31:00.001-07:00

Human Merkel cell polyomavirus infection I. MCV T antigen expression in Merkel cell carcinoma, lymphoid tissues and lymphoid tumors.
Int J Cancer. 2009 Apr

Shuda M, Arora R, Kwun HJ, Feng H, Sarid R, Fernández-Figueras MT, Tolstov Y, Gjoerup O, Mansukhani MM, Swerdlow SH, Chaudhary PM, Kirkwood JM, Nalesnik MA, Kant JA, Weiss LM, Moore PS, Chang Y.
Molecular Virology Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA.

Merkel cell polyomavirus (MCV) is a recently discovered human virus closely related to African green monkey lymphotropic polyomavirus. MCV DNA is integrated in approximately 80% of Merkel cell carcinomas (MCC), a neuroendocrine skin cancer linked to lymphoid malignancies such as chronic lymphocytic leukemia (CLL). To assess MCV infection and its association with human diseases, we developed a monoclonal antibody that specifically recognizes endogenous and transfected MCV large T (LT) antigen. We show expression of MCV LT protein localized to nuclei of tumor cells from MCC having PCR quantified MCV genome at an average of 5.2 (range 0.8-14.3) T antigen DNA copies per cell. Expression of this putative viral oncoprotein in tumor cells provides the mechanistic underpinning supporting the notion that MCV causes a subset of MCC. In contrast, although 2.2% of 325 hematolymphoid malignancies surveyed also showed evidence for MCV infection by DNA PCR, none were positive at high viral copy numbers, and none of 173 lymphoid malignancies examined on tissue microarrays expressed MCV LT protein in tumor cells. As with some of the other human polyomaviruses, lymphocytes may serve as a tissue reservoir for MCV infection, but hematolymphoid malignancies associated with MCC are unlikely to be caused by MCV.

PubMed

Human Merkel cell polyomavirus infection II. MCV is a common human infection that can be detected by conformational capsid epitope immunoassays.

2009-06-08T07:27:00.000-07:00

Human Merkel cell polyomavirus infection II. MCV is a common human infection that can be detected by conformational capsid epitope immunoassays.

Int J Cancer. 2009 Apr

Tolstov YL, Pastrana DV, Feng H, Becker JC, Jenkins FJ, Moschos S, Chang Y, Buck CB, Moore PS.
Molecular Virology Program, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA.

Merkel cell polyomavirus (MCV) is a newly-discovered human tumor virus found in approximately 80% of Merkel cell carcinoma (MCC). The rate of MCV infection among persons without MCC is unknown. We developed a MCV virus-like particle (VLP) enzyme-linked immunoassay (EIA) that does not cross-react with human BK or murine polyomaviruses. Peptide mapping of the MCV VP1 gene and immunoblotting with denatured MCV VLP are less sensitive than the MCV EIA in detecting MCV antibodies suggesting antibody reactivity in this assay primarily targets conformational but not linear epitopes. Among MCC patients, all 21 (100%) patients tested with MCV-positive tumors had high serum MCV IgG but not high MCV IgM levels. Only 3 of 6 (50%) MCC patients with MCV-negative tumors were positive for MCV antibodies. Sera from most adults, including 107 of 166 (64%) blood donors, 63 of 100 (63%) commercial donors and 37 of 50 (74%) systemic lupus erythematosus patients, show evidence for prior MCV exposure. Age-specific MCV prevalence was determined by examining a cross-sectional distribution of 150 Langerhans cell histiocytosis (an unrelated neoplasm) patient sera. MCV prevalence increases from 50% among children age 15 years or younger to 80% among persons older than 50 years. We did not find evidence for vertical transmission among infants. Although past exposure to MCV is common among all adult groups, MCC patients have a markedly elevated MCV IgG response compared with control patients. Our study demonstrates that MCV is a widespread but previously unrecognized human infection.

Wiley InterScience

Molecular pathogenesis of Merkel cell carcinoma

2009-05-19T08:14:00.001-07:00

Molecular pathogenesis of Merkel cell carcinoma

Exp Dermatol. 2009 Mar
Houben R, Schrama D, Becker JC.
Department of Dermatology, Julius Maximilians University, Würzburg, Germany.

Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine skin cancer which is twice as lethal as melanoma as more than one-third of MCC patients will die from this cancer. Although MCC, which primarily affects elderly and immune suppressed individuals, is very rare to date, its incidence is rapidly increasing. In contrast to the immense progress that has been made in the elucidation of the molecular pathogenesis of other cancer entities, until recently there were no clear-cut indications which events drive the carcinogenesis of MCC. Important findings published last year have changed this radically. Hypermethylation of the p14(ARF) promoter and a striking correlation between expression of p63 and the clinical course of MCC have been reported. Most important, however, is the discovery that MCC development in the majority of cases is preceded by the integration of genomic sequences of the hitherto unknown Merkel cell polyomavirus (MCPyV). Now a fundamental improvement in the understanding of MCC pathogenesis as well as the development of new therapeutic approaches based on this knowledge appear to be possible within the near future.

Wiley/InterScience

Merkel cell carcinoma--immunohistochemical study in a group of 11 patients

2009-05-19T08:09:00.000-07:00

Merkel cell carcinoma--immunohistochemical study in a group of 11 patients
Jirásek T, Matej R, Pock L, Knotková I, Mandys V.
Ustav patologie 3, LF UK a FNKV, Praha. tjirasek@fnkv.cz

The aim of our work was to confirm an immunohistochemical profile of routine markers of epithelial and neuroendocrine differentiation in eleven cases of Merkel cell carcinoma, as well as to study the expression of two markers of early phases of neuronal differentiation, namely reelin and class III beta-tubulin, markers which have not yet been studied in Merkel cell carcinomas. In all the investigated tumours the characteristic "dot-like" pattern of cytokeratin 20 immunoexpression, as well as negative immunostaining for cytokeratin 7 and thyroid transcription factor 1 (TTF-1) were disclosed; all the tumours showed neuroendocrine differentiation, expressing either neuron specific enolase (NSE) or chromogranin A(CgA), or both. An interesting finding was observed when the anti-cytokeratin monoclonal antibody MNF 116 was used. The characteristic "dot-like" pattern was detected in high proportion of tumours, including two samples of local recurrence of one of the carcinomas, where neoplastic cells have lost the expression of cytokeratin 20. The majority (91%) of Merkel cell carcinomas included in our group showed positive immunodetection of class III beta-tubulin when TU-20 antibody was used, while TuJ-1 immunostaining was surprisingly negative in all the investigated tumours. Detection of reelin was negative in almost all the studied Merkel cell carcinomas except for cases, where neoplastic cells revealed weak focal immunostaining in a minor portion of neoplastic cells.

PMID: 19402315 [PubMed - in process]

Merkel cell carcinoma: a review of current advances.

2009-05-19T08:05:00.000-07:00

Merkel cell carcinoma: a review of current advances.

Zhan FQ, Packianathan VS, Zeitouni NC.
Department of Dermatology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA. nathalie.zeitouni@roswellpark.org.

Merkel cell carcinoma (MCC) is a rare but aggressive cutaneous malignancy of neuroendocrine origin. Its incidence has tripled over the past 15 years. This article reviews the recent advancement in diagnosis, discoveries in pathogenesis, and updates in management. The acronym, AEIOU, has been proposed to aid in clinical identification. In addition to cytokeratin 20, newer immunohistochemical stains (in particular thyroid transcription factor-1 and neurofilament protein) have proven to be essential in pathologic diagnosis. Although immune suppression and ultraviolet radiation have long been associated with the MCC oncogenesis, recent studies also show involvement of a new polyomavirus and bcl-2. Several tumor classifications have been published in the literature, with the 4-tiered system from Memorial Sloan-Kettering Cancer Center the most widely used. A similar classification with additional distinctions among nodal disease is being constructed. A multidisciplinary treatment algorithm is recommended for MCC. Surgical excision with adjuvant radiotherapy (RT) is indicated for localized tumors. RT is favored over complete lymph node dissection and chemotherapy for regional lymph node involvement. For distant metastasis, management should be individualized with a combination of palliative surgery, RT, and chemotherapy.

PMID: 19401065 [PubMed - in process]

Reactivity with TdT in Merkel cell carcinoma: a potential diagnostic pitfall

2008-12-30T07:51:00.000-08:00

Reactivity with TdT in Merkel cell carcinoma: a potential diagnostic pitfall

Am J Clin Pathol. 2008 Jun

Buresh CJ, Oliai BR, Miller RT.
Immunohistochemistry Division, ProPath Laboratory, Dallas, TX 75247, USA.

Merkel cell carcinoma (MCC) is a high-grade neuroendocrine carcinoma of skin characterized by cells with a "blastic" appearance, scant cytoplasm, and fine, evenly distributed chromatin. Terminal deoxynucleotidyl transferase (TdT) is a DNA polymerase present in thymic T cells, lymphoblastic lymphoma/leukemia, and some cases of acute myeloid leukemia. After observing TdT immunoreactivity in a case of MCC, we analyzed 26 tumors by immunohistochemical analysis to determine their spectrum of reactivity with TdT and identified TdT in 19 (73%) of 26 MCCs. Staining intensity was variable but was often moderate to strong and present in a significant percentage of cells. Because MCC has cytomorphologic features similar to those of lymphoblastic lymphoma and may manifest as metastatic disease, reactivity with TdT in MCC could represent a diagnostic pitfall in the differential diagnosis with lymphoblastic lymphoma, particularly because the latter may lack CD45 and/or CD20, yet both neoplasms may express PAX-5, a B-cell-associated marker.

MetaPress American Journal of Clinical Pathology

Merkel cell carcinoma: molecular pathogenesis, clinical features and therapy.

2008-12-30T07:47:00.000-08:00

Merkel cell carcinoma: molecular pathogenesis, clinical features and therapy.

J Dtsch Dermatol Ges. 2008 Sep

Becker JC, Kauczok CS, Ugurel S, Eib S, Bröcker EB, Houben R.
Department of Dermatology, Venereology and Allergy, University of Würzburg, Germany. becker_jc@klinik.uni-wuerzburg.de

Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine carcinoma of the skin. The incidence of this rare tumor is increasing rapidly; the American Cancer Society estimates for 2008 almost 1500 new cases in the U.S. Thus, the incidence of MCC will exceed the incidence of cutaneous T-cell lymphoma. Moreover, the mortality rate of MCC with 33% is considerably higher than that of cutaneous melanoma. These clinical observations are especially disturbing as we are only recently beginning to understand the pathogenesis of MCC. For the same reason, the therapeutic approach is often unclear; reliable data are only available for the therapy of locoregional disease.

Wiley InterScience

Treatment Option Overview by Stage for Merkel Cell Carcinoma

2008-11-23T09:05:00.000-08:00

Treatment Option Overview by Stage for Merkel Cell Carcinoma

How Merkel cell carcinoma is treated

There are treatments for all patients with Merkel cell carcinoma. Three kinds of treatment are used:

surgery (taking out the cancer)

radiation therapy (using high-dose x-rays or other high-energy rays to kill cancer cells)

chemotherapy (using drugs to kill cancer cells)

There are several different types of surgery that may be used to remove the tumor. These include:

Wide surgical excision takes out the cancer and some of the skin around the tumor.

Cryosurgery freezes the tumor and then removes it.

Micrographic surgery is a tissue-sparing technique that removes only the tumor.

Radiation therapy uses high-energy x-rays to kill cancer cells and shrink tumors.

Radiation may come from a machine outside the body (external radiation therapy) or from putting materials that produce radiation (radioisotopes) through thin plastic tubes in the area where the cancer cells are found (internal radiation therapy).

Chemotherapy uses drugs to kill cancer cells. Chemotherapy may be taken by pill, or it may be put into the body by a needle in a vein or muscle. Chemotherapy is called a systemic treatment because the drugs enter the bloodstream, travel through the body, and can kill cancer cells throughout the body.

If a doctor removes all the cancer that can be seen at the time of the operation, a patient may be given chemotherapy after surgery to kill any cancer cells that are left. Chemotherapy given after an operation to a person who has no cancer cells that can be found is called adjuvant chemotherapy.

STAGE I MERKEL CELL CARCINOMA

Treatment may be one of the following:

1. Surgery alone.

2. Surgery followed by radiation therapy to the tumor site and regional lymph nodes.

STAGE II MERKEL CELL CARCINOMA

Treatment may be one of the following:

1. Surgery alone.

2. Surgery followed by radiation therapy to the tumor site and regional lymph nodes.

3. Surgery with or without radiation therapy followed by adjuvant chemotherapy.

STAGE III MERKEL CELL CARCINOMA

Treatment will probably be chemotherapy.

RECURRENT MERKEL CELL CARCINOMA

Treatment may be one of the following:

1. Surgery alone.

2. Surgery followed by radiation therapy to the tumor site and regional lymph nodes.

3. Surgery with or without radiation therapy followed by adjuvant chemotherapy.

Cancer Web UK

Stages of Merkel cell carcinoma

2008-11-23T09:01:00.000-08:00

Stages of Merkel cell carcinoma
Stage Explanation

After Merkel cell carcinoma has been diagnosed (found), more tests will be done to find out if cancer cells have spread from the place the cancer started to other parts of the body. The process used to find out whether the cancer has spread to other parts of the body is called staging. It is important to know the stage of the disease to plan the best treatment. The following stages are used for Merkel cell carcinoma:

Stage I

The primary tumor has not spread to lymph nodes or other parts of the body. Lymph nodes are small, bean-shaped structures that are found throughout the body. They produce and store infection-fighting cells.

Stage II

The cancer has spread to nearby lymph nodes, but has not spread to other parts of the body.

Stage III

The cancer has spread beyond nearby lymph nodes and to other parts of the body.

Recurrent stage

Recurrent disease means that the cancer has recurred (come back) after it has been treated. It may come back in the same part of the body or in another part of the body.

Cancer Web UK

Merkel cell carcinoma: outcome and role of radiotherapy

2008-11-23T08:51:00.000-08:00

Merkel cell carcinoma: outcome and role of radiotherapy

Cancer Radiother. 2008 Sep

Salvador Alonso R, Lahbabi I, Ben Hassel M, Boisselier P, Chaari N, Lesimple T, Chevrier S, de Crevoisier R.

Département de radiothérapie, centre Eugène-Marquis, avenue Bataille-Flandres-Dunkerque, 35042 Rennes, France.

Merkel cell carcinoma (MCC) are rare neuroendocrine malignant tumor of the skin, occurring in elderly patients. It affects primarily the sun-exposed areas of the skin, with approximately 50% of all tumors occurring in the face and neck and 40% in the extremities. Immunohistochemical markers (CK20+, CK7- and TTF1-) are used to distinguish between MCC and other tumors. MCC have a tendency to rapid local progression, frequent spread to regional lymph nodes and distant metastases. Due to the rarity of the disease, the optimal treatment has not been fully defined. Localized stages (stages I and II) are treated by surgical excision of the primary tumor (with 2 to 3 cm margin) and lymphadenectomy in case of node-positive disease, followed by external beam radiotherapy (EBRT) to a total dose of 50 to 60Gy in the tumor bed. Adjuvant EBRT has been shown to decrease markedly locoregional recurrences and to increase survival in recent studies. Treatment of lymph nodes area is more controversial. Chemotherapy is recommended only for metastatic disease.

Eslevier

Merkel cell carcinoma: histologic features and prognosis.

2008-11-12T05:18:00.000-08:00

Merkel cell carcinoma: histologic features and prognosis.
Cancer. 2008 Nov

Andea AA, Coit DG, Amin B, Busam KJ.
Department of Pathology, Memorial Sloan- Kettering Cancer Center, New York, New York, USA. aandea@uab.edu

BACKGROUND: Currently, little is known regarding the potential prognostic value of histologic features in primary cutaneous neuroendocrine (Merkel cell) carcinomas (MCC).

METHODS: In a retrospective review of the tumor histology and clinical outcome data (median follow-up, 51 months; range, 3-224 months) of 156 patients with a diagnosis of MCC, the following histologic features were evaluated: tumor thickness, tumor size (greatest dimension of the tumor), microanatomic compartment involved by tumor (dermis and/or subcutis and/or deeper), tumor growth pattern (nodular circumscribed vs infiltrative), lymphovascular invasion (LVI), tumor-infiltrating lymphocytes, tumor necrosis, ulceration, and solar elastosis.

RESULTS: The overall 5-year survival rate was 67.5%. On univariate analysis, parameters that were associated significantly with survival were tumor thickness (P= .001), tumor size (P= .0002), deepest anatomic compartment involved by tumor (P= .0003), tumor growth pattern (P= .003), LVI (P< .00001), tumor-infiltrating lymphocytes (P= .05), and solar elastosis (P= .04). On multivariate analysis, the presence of a nodular growth pattern, low tumor depth, and absence of LVI were associated with longer survival.

CONCLUSIONS: In addition to the known prognostic value of tumor stage, 3 histologic features were identified to have prognostic significance: tumor thickness (depth of tumor invasion), the presence of LVI, and tumor growth pattern.

Wiley InterScience

Merkel cell carcinoma within follicular cysts: report of two cases.

2008-11-12T05:10:00.000-08:00

Merkel cell carcinoma within follicular cysts: report of two cases.
Requena L, Jaqueti G, Rütten A, Mentzel T, Kutzner H.

Department of Dermatology, Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain.

Merkel cell carcinoma is a rare cutaneous neoplasm of unknown histogenesis. Several reports have described the association of Merkel cell carcinoma of the skin with other cutaneous neoplasms within the same lesion, and there are also reports describing three examples of Merkel cell carcinoma within follicular cysts. We describe two examples of Merkel cell carcinoma developed within epithelial cysts. Neoplastic cells of Merkel cell tumor expressed immunoreactivity for chromogranin, synaptophysin, neuron-specific enolase, CAM 5.2 and cytokeratin 20, the last two markers showing the characteristic paranuclear dot-like pattern. In contrast, the epithelial wall lining the cyst and surrounding Merkel cell tumor only expressed immunoreactivity for cytokeratin MNF116. The description of five cases of Merkel cell carcinoma within follicular cysts, including the two cases of this report, support some relationship between Merkel cell tumor and the hair follicle.

J Cutan Pathol. 2008 Dec

PMID: 18988316 [PubMed - in process]

Merkel Cell Carcinoma

2008-11-04T06:10:00.000-08:00

Merkel Cell Carcinoma

MD Anderson Cancer Center

Merkel Cell Carcinoma

Merkel Cell Carcinoma (MCC) is a rare skin malignancy which was first described in 1972 by Cyril Toker. However, the name Merkel cell comes from the anatomist who discovered the normal Merkel cell in pig snouts - Friedreich Sigmund Merkel in 1875. Because of the tumor cell characteristics seen under the microscope, the name neuroendocrine carcinoma of the skin is used synonymously with Merkel cell carcinoma.

The true incidence of this cancer is not known, but 400 - 600 cases have been described in the literature. Merkel cell carcinoma is almost exclusively seen in Caucasian people, and most are more than 65 years old. Some of the literature reports that MCC affects men and women equally, but other studies have shown a male predominance. The etiology of this tumor is not clearly defined, but there has been association of MCC to sun exposure. Many of the patients have a history of other basal or squamous cell cancers of the skin, and approximately 10% of the patients will develop a second primary cancer.

Merkel cell carcinoma most commonly occurs in the skin of the head and neck (50%), followed by the extremities and the trunk. The head and neck, cheek, forehead, temple, nose, and upper neck are the most common sites. This tumor is innocuous in appearance - described as a painless, solitary, raised, pink nodule. Most tumors are less than 2 cm when initially discovered. Biopsy is the only way to diagnose MCC. However, the diagnosis is difficult for most pathologists, and requires both the use of the electron microscope and special staining of the cells to differentiate it from other small cell carcinomas.

Merkel cell carcinoma is a very aggressive cancer. Lymph node metastasis occurs early and often. Some studies report palpable lymph nodes at presentation in 45% of patients. However, distant metastasis is rare at presentation. Local and regional recurrence occurs frequently, and is felt to be related to the adequacy of the initial therapy. Distant metastasis occurs in approximately 25% of patients, regardless of therapy.

The current thoughts on treating Merkel cell cancer include both the primary lesion and the regional lymphatics. It is felt that the primary cancer should be surgically removed with negative margins. Studies have shown that surgical treatment alone has a higher rate of local and regional recurrence that those who receive surgical excision and radiation therapy. Thus, after the tumor is removed, 6 weeks of radiation to the surgical site and to the regional lymphatics is recommended. However, despite this aggressive therapy, approximately 40% still develop locoregional recurrence.

It is felt that regardless of therapy, 25 - 35% of patients may ultimately recur. It is felt that the development of locoregional recurrence is a predictor of multiple recurrence and distant metastasis. Thus, it is implied that early locoregional treatment will improve tumor control. However, it is not proven whether locoregional control will affect the rate of distant metastasis and ultimately affect survival.

Merkel cell carcinoma. On one case

2008-11-04T05:51:00.000-08:00

Merkel cell carcinoma. On one case

An Sist Sanit Navar. 2008 May-Aug

Cires Bezanilla M, González C, Jiménez F, Rubio T, Amat I.
Servicio de Cirugía General, Hospital García Orcoyen, Estella, 31200, Spain. mcires@gmail.com.

We present the case of an 86 year old woman who was sent for consultation at General Surgery due to asymptomatic tumouration on the back face of the left thigh whose size had increased during the 2 previous months. Physical exploration revealed tumouration that was painless, excrescent, indurated, mobile and well delimited, with a diameter of 5 cm, a reddish colour and a rough surface. Tumoural extirpation was carried out with broad margins, with a hystopathological result of primary cutaneous neuro-endocrynal carcinoma or Merkel cell carcinoma. Computerised tomography was carried out, observing tumoural adenopathies in the para-aortic spaces, iliac chains and left femorals, as well as edema in the lower left extremity.

The patient was sent to the Oncology service for treatment, without presenting a satisfactory evolution and with a progressive deterioration of her general state, dying within the first year after diagnosis.

Anales

What is Merkel cell carcinoma?

2008-10-26T11:33:00.000-07:00

What is Merkel cell carcinoma?

Merkel cell carcinoma (MCC) is a rare, aggressive type of skin cancer that forms on or just under the skin. It is also called primary small cell carcinoma of the skin, trabecular carcinoma, APUDoma, neuroendocrine carcinoma, endocrine carcinoma, or primary undifferentiated tumor of the skin. MCC is believed to start in neuroendocrine cells called Merkel cells. These cells release hormones into the blood when stimulated by the nervous system. They migrate from part of the nervous system called the neural crest to the skin. Merkel cells are believed to play a role in making the skin sensitive to touch.

How often does Merkel cell carcinoma occur?

Approximately 1,200 new cases of MCC are diagnosed in the United States each year, compared with almost 60,000 new cases of melanoma and more than 1 million new cases of nonmelanoma skin cancer. The incidence of MCC has been rising, with a 3-fold increase between 1986 and 2001. Most patients diagnosed with MCC are over age 50 at diagnosis (the average age is 69), with only 5 percent of cases diagnosed in those under age 50. MCC is more common in white people than in other racial/ethnic groups. Some cases have been reported in Japanese people, but very few have been seen in black people.

What are the possible causes of Merkel cell carcinoma?

The exact cause of MCC is unknown, but it appears to be linked to sun exposure and immunosuppression (suppression of the body's immune system and its ability to fight infections or disease). Sun exposure as a risk factor for MCC is supported by data that show a rise in incidence corresponding with the solar UVB index (scale indicating the intensity of solar ultraviolet-B (UVB) radiation at noon for a particular location). MCC has been linked to conditions such as HIV infection, chronic lymphocytic leukemia, Hodgkin lymphoma (cancer of the lymph system), ectodermal dysplasia (a disease involving abnormal tissue development), and Cowden disease (a disease in which masses of abnormal but benign tissues grow in multiple sites in the body). Other possible causes include exposure to arsenic and treatment for psoriasis that uses psoralens (a medication that causes the skin to become sensitive to light) and ultraviolet-A light (PUVA).

What are the symptoms of Merkel cell carcinoma?

The most common symptom of any skin cancer, including MCC, is a change in the skin, especially a change in an existing mole or a new growth. MCC appears as a firm, painless lump within the skin that may resemble a cyst but is fixed; i.e., cannot be moved. The lump is usually less than 2 cm (about ¾ inch) in size and can be red, pink, or blue-violet. MCC is different from other skin cancers in that it grows rapidly over a few weeks or months.

Where does Merkel cell carcinoma develop?

MCC is usually found on sun-exposed areas of the body. Fifty percent of cases occur on the head and neck, especially around the eye and on the eyelid. Forty percent of cases occur on the arms and legs. MCC has also been found on the trunk and other areas of the skin that are not usually exposed to the sun.

How is Merkel cell carcinoma diagnosed and staged?

The doctor may use the following procedures and tests to diagnose MCC. Some of these tests are also used to help determine the stage of the disease. Stage is a description of the extent of cancer.

A biopsy is the removal of cells or tissue from a tumor for examination by a pathologist. The pathologist may study tissue samples under a microscope or perform other tests on the cells or tissue. Biopsies are used for both diagnosis and staging. The surgeon may also remove lymph nodes (small, round organs that trap cancer cells, bacteria, or other harmful substances) to help determine the stage of the disease.

Sentinel lymph node (SLN) biopsy is a procedure in which the sentinel lymph node is removed and examined under a microscope to determine whether cancer cells are present. The sentinel lymph node is the first lymph node to which cancer is likely to spread from the primary tumor. SLN biopsy is used to help determine the stage of the disease. SLN biopsy may cause fewer side effects than standard lymph node removal because fewer lymph nodes are taken out.
Immunohistochemistry (staining of cells with agents that react with antibodies on the surface of cancer cells) is a laboratory technique used to tell the difference between MCC and other types of cancer.

Computed tomography (CT), a procedure that uses special x-ray equipment to obtain cross-sectional pictures of the body, can distinguish MCC from small cell lung cancer and show whether the disease has metastasized (spread) to other parts of the body.

In an octreotide scan (sometimes called Somatostatin Receptor Scintigraphy or SRS), the doctor injects a small amount of a radioactive drug into a vein. The drug travels through the bloodstream and attaches to tumor cells. A machine called a scanner detects the radioactive material and creates scans (pictures) showing where the tumor cells are located in the body. For MCC, this test can be used for both diagnosis and staging.

A PET scan uses radioactive sugar, which is absorbed by cancer cells and appears as dark areas on the scan. It can be used for both diagnosis and staging of MCC.

How is Merkel cell carcinoma treated?

Surgery is the most common treatment for MCC. Surgery with wide margins (a large border of healthy tissue removed with the tumor) is the recommended treatment for MCC. Mohs micrographic surgery, a technique in which individual layers of tissue are removed and examined under a microscope until all cancerous tissue has been removed, may be used instead of traditional surgery with wide margins. Mohs micrographic surgery may be a good alternative for MCC tumors on highly visible areas such as the face, and in areas where the surgeon would not be able to obtain wide margins.

The surgeon may remove lymph nodes to help stage the disease or to prevent recurrence (cancer coming back). The patient may also receive adjuvant radiation therapy (treatment given after the primary therapy) to decrease the chance of recurrence. Chemotherapy is the usual treatment if the disease has spread beyond the lymph nodes to areas that are not treatable by radiation therapy.

Supportive care is treatment given to improve the quality of life of patients who have a serious or life-threatening disease, such as cancer. It prevents or treats as early as possible the symptoms of the disease, side effects caused by treatment of the disease, and psychological, social, and spiritual problems related to the disease or its treatment. For example, anticancer drugs such as carboplatin and etoposide may be given to relieve symptoms in some patients with MCC. Radiation may be used to relieve pain from MCC that has metastasized to the brain or bones, and to reduce discomfort from skin problems associated with MCC (2). Additionally, meeting with a social worker, counselor, or member of the clergy can be helpful to those who want to talk about their feelings or discuss their concerns. A social worker can often suggest resources for help with recovery, emotional support, financial aid, transportation, or home care.

Are clinical trials (research studies) available? Where can people get more information about clinical trials?

Yes. The National Cancer Institute (NCI), a component of the National Institutes of Health, is sponsoring clinical trials that are designed to find new treatments and better ways to use current treatments. Before any new treatment can be recommended for general use, doctors conduct clinical trials to find out whether the treatment is safe for patients and effective against the disease. Participation in clinical trials may be a treatment option for patients with MCC.

What is the prognosis for patients with Merkel cell carcinoma?

Prognosis describes the likely course and outcome of a disease—that is, the chance that a patient will recover or have a recurrence. The prognosis for MCC patients depends greatly on the stage of the disease at the time of diagnosis. If the tumor is small (less than 2 cm or about ¾ inch) and cancer cells have not spread to the lymph nodes, the 5-year survival rate is more than 90 percent. Patients with MCC that has spread to the lymph nodes have a 5-year survival rate of about 50 percent. Overall 5-year survival for patients diagnosed with MCC is 64 percent, but half of patients with advanced MCC will live only 9 months. The disease recurs in about 50 percent of patients. It is important to keep in mind, however, that these statistics are averages based on large numbers of patients. Statistics cannot be used to predict what will happen to a particular patient because each person's situation is unique.

National Cancer Instsitute