Abstract
The research paper deals with the problem of Merkel cell carcinoma, chief peculiarities, and the possibility of medical treatment. Disease signs and symptoms are highlighted in the opening and subsequent paragraphs of the paper. The pathophysiology, etiology, manifestations, possible complications, and disease treatment are the focal point of the research paper. The research is based on the opinions of the finest subject-field experts, such as professors, doctors, and scientists.
Keywords: Merkel cell carcinoma, medical treatment, disease, complication, cure
Merkel cell carcinoma is an aggressive skin cancer usually caused by polyomavirus. Scientists and doctors have not managed to research this medical phenomenon properly, which accounts for the high incidence of mortality. As any rare type of disease, MCC has its target patients, as it affects people of certain ages, race, and health conditions. If left untreated, this illness may assume heavier shape and produce long-term complications. Even so, Merkel cell carcinoma is subject to different types of medical treatment. Plenty of human organism pathologies generate the disease that is supposed to cause inflammatory response, with regeneration process being a required procedure. Sondak, Messina, Zager, and DeConti (2011) noted that Merkel cell carcinoma was an infrequent invasive skin cancer characterized by regional distant and nodal metastases, the high scope of local recurrences, and the high incidence of mortality. Disease-induced disordered physiological processes studies by pathophysiology develop in Merkel cells that are allowedly of neuroendocrine origin. Identified as “touch cells” by Sigmund Merkel back 1875, Merkel cells are located in the basal layer of epidermis in immediate contact with the so-called nerve terminals as well as performing the functions of mechanoreceptors, or sense cells responsive to such mechanical incentives, as sounds or touch.
With age-adjusted rate of 3.2 per 1 million individuals in the USA, Merkel carcinoma is difficult to research. Not only that, but the puzzling differential diagnosis with other metastatic and primary skin cancers along with origin obscurity obstructs researches on disease etiology, risk factors, and therapeutic approaches. The etiological factors of MCC remain poorly identified. As per the recent compilation and scrutiny of multiple subject-field studies, the exposure to ionizing radiation, ultraviolet A and B radiation, and infrared radiation is believed to be one of the principal causes of the disease. Recognized as a risk factor for malignant melanoma and non-melanoma skin cancers, sun exposure is an essential factor in MCC etiology. Chronic thermal radiation exposure may produce erythema, or the patch-like skin reddening that causes the dilatation of blood capillaries. Merkel cell carcinoma stems from old burns as well as the regions of erythema alone or accompanied by squamous cell carcinoma.
In 1960s, scientists have established a connection between skin cancer and the exposure to arsenic-contaminated water. In underdeveloped countries, arsenic is a widespread carcinogen that affects human health by causing mitochondrial detriment since it is a chromosome mutagen and a potent gene. Apart from enhancing the possibility of the cancers of the lympho-hemopoietic system and organ cancers, inorganic arsenicals enhance the risk of skin cancer. Viral infection is another cause of the disease, with polyomavirus identified in MCC tissue and labeled as Merkel cell polyomavirus. Researchers have found iatrogenic immunosuppression and Merkel cell carcinoma to be associated. Patients diagnosed with any of autoimmune diseases, as systemic lupus erythematosus, rheumatoid arthritis, Wegener’s granulomatosis, Behcet’s syndrome, chronic sarcoidosis, and autoimmune hepatitis.
Lymphocytes or antibodies generated against substances that are naturally present in a human body usually cause such autoimmune illnesses. Patients who undergo the transplantation of organs, as bone marrow, heart, and liver, to name a few, may develop Merkel cell carcinoma, with transplantation directly related to immunosuppression. Individuals diagnosed with the AIDS face the relative possibility of developing MCC, as opposed to the general population. The enhanced risk among AIDS patients accounts for immune system detriment produced by human immunodeficiency virus that makes such people vulnerable to viral and bacterial infections, and cancer development. A number of scientists have linked MCC to other cancers, most notably lympho-hemopoietic or skin cancers. Finally, squamous cell carcinomas are assumed to predispose to the development of MCC.
As far as MCC manifestations are concerned, nondescript painless lesions may emerge on the sun-exposed white skin of elderly individuals who seek medical aid due to the rapid growth of such skin formations. Such disease transpires in the shape of a symptom-free, solitary, small-sized red-purple hypodermic indurated blood-plate or nodule, and often defies diagnosis until histopathologically examined. Its signs and symptoms make themselves felt on sun-exposed regions of neck or head skin in 48% of cases registered. Mere 5% of overall cases MCC is to be observed at mucosal anatomic sites while in as many as 54% of observations larynx is the affected area. Men have head and neck affected by the disease while women usually get their trunk infected.
According to a National Cancer Institute (2014), MCC emerges as painless, firm, and shiny lumps of skin. Such lumps, aka tumors, may differ in size from less than a quarter of an inch to almost more than several inches. They can be pink, red, or blue in color. Arms, legs, head, and neck exposed to thermal radiation are the target regions of human body. Patients of all races between the ages of 60 and 80 may be prone to developing Merkel cell carcinoma irrespective of skin color (National Cancer Institute, 2014). Ho, Tsai, Lee, and Guo (2005) suggested that MCC affected mostly male patients who outnumber females by 2 or even 3 to 1. The average age threshold was lowered to 70 years while the starting point of disease development was recorded at 60 years (Ho, et al., 2005). Overall, such cutaneous formation evokes no pain, grows fast, ranges from violet to red in color, has a dome shape, and may occur among all races.
Merkel cell carcinoma has its own complications that may ensue if no adequate medical treatment is provided. According to Eggers, Salomao, Dinapoli, and Vernino (2001), such skin neuroendocrine tumor is believed to be locally aggressive and often accompanied by distant metastases. As such, it rarely causes complications. However, when it does, patients with autoimmune diseases, such as, for example, Lambert-Eaton myasthenic syndrome characterized by muscle weakness of limbs may develop MCC that may evolve into a solitary brain metastasis and eventual biological demise. Scientists opine that there is always the possibility of patients’ acquiring metastatic and paraneoplastic neurologic complications from this unusual skin neuroendocrine tumor. Experts conducting observations have found patients to develop MCC-induced leptomeningeal and parenchymal metastases, which is indicative of cell carcinoma affecting internal organs and brain when secondary malignant growths evolve (Eggers, et al., 2001).
According to the National Cancer Institute (2013), there are different stages of disease development that demonstrate the scope of possible complications. In stage zero, or carcinoma in situ, pathological cells remains within the nidus of the illness, without spreading to the distant body parts or lymph nodes. During stage IA, such tumor may reach 2 centimeters in size while stage IB produces swollen lymph nodes besides a similar two-centimeter growth. During IIA and IIB stages, no cancer and swollen lymph are to be observed, with a patch of inflamed skin excels two centimeters. When it comes to stage IIC, tumor may already reach any size spreading to nearby muscles, bones, cartilage, or connective tissues, though not affecting distant body parts or lymph nodes. In the course of IIA and IIB stages, the scope of detriment is similar with the difference that cancer damages lymph nodes. Stage V sees tumor assume any size, which usually reaches up to 5 centimeters, and spread to distant body parts, such as bone, liver, lung, or brain. Experts use pea, peanut, walnut, and lime as benchmarks to evaluate the scope of damage done (The National Cancer Institute, 2013). As may be deduced from the above, the original red patch of 1 centimeter may quintuple, gradually affecting lymph nodes, distant body parts, and vital internal organs.
According to National Cancer Institute (n.d.), the lack of cohesive and systematic compilation of treatment methodology due to incomplete clinical trials and treatment protocols baffles the analysis of possible techniques. One of viable options is surgery for the primary lesion. Some experts speak in favor of applying such tissue-sparing method as Mohs micrographic surgery. The National Cancer Institute (2013) suggested that doctors might perform wide regional excision, by which they cut tumor from the skin together with cutis around it, with specialists performing a sentinel lymph node biopsy during such procedures. A lymph node dissection becomes a necessity when cancer has affected lymph nodes. Cancer clinical treatment also implies radiation therapy that applies high-energy x-rays as well as other kinds of radiation to exterminate tumor cells. External therapy utilizes a machine outside human body in order to direct radiation to the nidus of cancer. Internal analogue applies radioactive substances hermetically sealed in seeds, needles, catheters, or wires placed into the cancer or in close proximity to such. Chemotherapy implies the application of drugs that hamper the growth of tumor cells by exterminating such or preventing from dividing. When injected into a muscle or vein or taken by mouth, drugs reach cancer cells after entering the bloodstream. Unlike such systematic chemotherapy, its regional analogue is placed into an organ, the cerebrospinal fluid, or a body cavity, as the abdomen. In such case, drugs target tumor cells regionally (The National Cancer Institute, 2013).
Pathological processes are abnormalities or dysfunctions of organs and tissues. Such processes are the deviations from physiologically acceptable norms. While the exposure of skin to radiation does not produce direct pathological processes, the regions of endemic arsenicism, according to Sondak, Messina, Zager, and DeConti (2011), are prone to MCC. Ho, Tsai, Lee, and Guo (2005) claimed that long-dated exposure to such carcinogen as inorganic arsenic could result in people’s developing visceral malignant swelling in cutis. Hence, such pathological process as the poisoning with arsenic is the direct stimulus of Merkel cell carcinoma. Sondak, Messina, Zager, and DeConti (2011) suggested that such pathological processes as viral infections, immunosuppression induced by organ transplantation, and acquired immunodeficiency virus produced Merkel cell carcinoma affecting skin cells and tissues.
Immunosuppression is the neutralization of immune system, which is the system of organs composed of organs and tissues protecting the body from infections by identifying tumor cells and pathogens, or disease causing viruses and bacteria. Thus, normal physiological processes that protect a human organism are suppressed, which creates a deviation from normal functioning, or pathology that, in turn, produces favorable conditions for the development of Merkel cell carcinoma. Such pathology as the absence of immune system may leave organism exposed to Merkel cell polyomavirus that is, according to Wheat, Roberts, Waterboer, Steele, Marsden, Steven, and Blackbourn (2014), integrated within malignant cells. Human immunodeficiency virus also gradually erodes human immune system, posing a serious pathology that increases organism vulnerability to opportunistic infections and tumors, as Merkel cell carcinoma. Sondak, Messina, Zager, and DeConti (2011) noted that such pathologies as squamous cell carcinomas, lympho-hemopoietic, and skin cancers predisposed to the development of MCC.
Wheat, Roberts, Waterboer, Steele, Marsden, Steven, and Blackbourn (2014) noted that almost all the tissue specimens handpicked for research except for two had inflammatory cells. Such cells were proved to follow identical patchy distribution concentrated at the edge of nodules, sheets, and more intense in trabecular regions in separate cases. In short, various inflammatory cells were arranged around the margin of malignant deposits, which suggested response to aberrant signaling, but proved unable to permeate through the microenvironment of tumor to cause an immune response against malignant cells or their polyomavirus (Wheat, 2014). In other words, inflammatory process is the defensive reaction of an organism and its immune system composed of tissues among others. Cells are the building material of tissues that protect the whole organism as a part of the complex immune system. Since such inflammatory cells were unable to penetrate into tumor cells to cause an immune response against the malignant skin formation, there might have been no reddening and inflammation observed among patients as a reaction to an infection and a visually represented attempt to counteract it.
Thus, in penetrating into malignant deposits and tumor microenvironment induced by the above-mentioned pathologies, as, for instance, immunodeficiency, inflammatory cells are supposed to produce an appropriate response, or immune reaction visible through skin reddening. With immune system capacities neutralized or critically diminished, inflammatory cells, its integral parts are slow to produce appropriate reaction, if at all. Cells produce a regional reaction in the areas where pathological processes are under way. Inflammatory cells are to isolate the affected or tumor cells from healthy ones. Inflammation is allowedly the initial response to a body infection manifested through pain, swelling, heat, and redness due to the intensification of blood stream into the tissue affected. Since heat and pain are not the case among MCC patients while redness is not to be observed in the majority of cases recorded, the immune system might not respond to inflammatory cells signals the way it should owing to the adverse impact of pathologies. Following a conventional inflammatory process, there comes a complete convalescence. Seeing that the only way to cure Merkel cell carcinoma is by clinical treatment, the inflammatory response does not produce a needed reaction from the immune system that would otherwise cause pain, heat, and redness. MCC patients report neither pain, nor heat in the region of infection.
Compton, Regauer, Seiler, and Landry (1990) studied the regeneration of human Merkel cells in epidermis that stemmed from cultured keratinocyte autografts, or the grafts of tissue. Regenerated MCs were never innervated, or supplied with nerves, while their emergence was not related either temporally or spatially to epidermal re-innervation. In the so-called skin bridges of meshed split-thickness grafts, such Merkel cells managed to survive following the degeneration of associated neuritis. Still, zero MCs emerged within re-epithelialized interstices (Compton, et al., 1990). Autographs injected contained keratinocyte, a specific epidermal cell that generates keratin, which is a special protein tasked with forming the external layer of human skin. In performing excision, doctors cut out the region of infected skin; hence, such grafts may regenerate the missing skin with epidermis, thus filling in the void. Such approach seems viable; however, scientists and doctors seem to have faced the issue, as regenerated Merkel cells do not become innervated, which means they do not acquire nerve endings and other essential constituents. That being said, scientists have yet to research the process of Merkel cell regeneration to restore the excised human skin.
Conclusions
Merkel Cell carcinoma is an aggressive skin cancer that has a high incidence of mortality. As such, it targets the elderly people between the ages of 60 and 80, producing no pain, zero symptoms, and blood-plate skin patch that varies from red or purple to blue. It affects neck, head, face, body, and limbs, with trunk being affected among female patients and neck and head areas among males. Patients may sometimes develop metastatic and paraneoplastic neurologic complications while the lack of adequate clinical treatment is likely to cause damage to lymph nodes, bones, livers, lungs, or even brain, which depends on the stage of the disease. By curing Merkel cell carcinoma, doctors may apply the excision of affected skin parts, lymph nodes dissection, chemotherapy, and radiation therapy. MCC may be created by such pathological processes as arsenic exposure, thermal radiation, and immunodeficiency induced by suppression following organ transplantation, or the acquisition of the human immunodeficiency virus.
Such pathological processes are the ones that lead to tissue and cell damage. Study observations suggest that inflammatory cells cannot penetrate through the tissue to cause the response from the immune system. If they did, there would possibly be peculiar swelling, heat, and pain that re not the case among MCC patients. Of course, there is a relative swelling and occasional redness. Due to the immune system with diminished efficiency, such inflammatory cells may be unable to evoke its adequate response, which would otherwise result in complete convalescence. The absence thereof necessitates clinical treatment. Scientists have come up with the idea of performing regeneration graft injections following excisions; however, the process of tissue re-innervation leaves much to be studied here.
References
A National Cancer Institute. (2014). Symptoms of Merkel Cell Carcinoma. Stanford Medicine. Retrieved from: http://cancer.stanford.edu/skincancer/merkel_cell_carcinoma/symptoms.html
Compton, C.C., Regauer, S., Seiler, G.R., and Landry, D.B. (1990). Human Merkel cell regeneration in skin derived from cultured keratinocyte grafts. Lab Invest, 63(2), 233-241. Retrieved from: http://www.ncbi.nlm.nih.gov/pubmed/1696332
Eggers, S.D.Z., Salomao, D.R., Dinapoli, R.P., and Vernino, S. (2001). Paraneoplastic and metastatic neurologic complications of Merkel cell carcinoma. Mayo Clinic Proceedings, 76, 327-330. Retrieved from: http://www.mayoclinicproceedings.org/article/S0025-6196(11)62897-8/pdf
Ho, S-Y., Tsai, Y-C., Lee, M-C., Guo, H-R. (2005). Merkel cell carcinoma in patients with long-term ingestion of arsenic. Journal of Occupational Heath, 47, 199-192. Retrieved from: https://www.jstage.jst.go.jp/article/joh/47/2/47_2_188/_pdf
National Cancer Institute at the National Institutes of Health. (n.d.). Merkel cell carcinoma Treatment. Cancer.gov. Retrieved from: http://www.cancer.gov/cancertopics/pdq/treatment/merkelcell/healthprofessional/page1/AllPages
Sondak, V.K., Messina, J.L., Zager, J.S., and DeConti, R.C. (2011). Merkel cell carcinoma. A multidisciplinary approach. Imperial College Press. Retrieved from: http://books.google.com.ua/books?id=uI6I85V3Ro8C&printsec=frontcover&dq=Merkel+Cell+Carcinoma&hl=uk&sa=X&ei=N0qAU4aTJIefyQP3loGYAQ&redir_esc=y#v=onepage&q=Merkel%20Cell%20Carcinoma&f=false
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Wheat, R., Roberts, C. Waterboer, T., Steele, J., Marsden, J., Steven, N.M., and Blackbourn, D.J. (2014). Inflammatory cell distribution in primary Merkel cell carcinoma. Cancers, 6, 1047-1064. doi: 10.3390/cancers6021047
