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Merkel cell carcinoma (MCC) is an aggressive skin cancer that is causally associated with ultraviolet light exposure and a recently discovered polyomavirus. Before 2010, MCC was staged using any of 5 unique systems in active use. In 2010, a consensus staging system for MCC was adopted worldwide and replaced these systems. This consensus system incl...
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Context 1
... represents a major expansion of ICD-9, and will increase the number of codes by roughly 10- fold across all diseases. With respect to MCC diag- nosis, the increasing number of codes affords greater specificity for anatomic site, including unique codes for laterality (Table 2). Despite a delay in implemen- tation, health care systems in the United States are expected to continue the transition to ICD-10. ...
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Background
Approximately 15% of human cancers are attributed to viruses. Numerous studies have shown that high-risk human polyomaviruses (HR-HPV) and Merkel cell polyomavirus (MCPyV) are two human tumor viruses associated with anogenetal and oropharyngeal cancers, and with Merkel cell carcinoma, respectively. MCPyV has been found in HR-HPV positive...
The pocket protein (PP) family consists of the three members RB1, p107 and p130 all possessing tumor suppressive properties. Indeed, the PPs jointly control the G1/S transition mainly by inhibiting E2F transcription factors. Notably, several viral oncoproteins are capable of binding and inhibiting PPs. Merkel cell polyomavirus (MCPyV) is considered...
Understanding and augmenting cancer-specific immunity is impeded by the fact that most tumors are driven by patient-specific mutations that encode unique antigenic epitopes. The shared antigens in virus-driven tumors can help overcome this limitation. Merkel cell carcinoma (MCC) is a particularly interesting tumor immunity model because (1) 80% of...
Introduction:
Merkel cell carcinoma (MCC) is an aggressive skin cancer, related to the Merkel Cell Polyomavirus (MCPyV) in 80% of cases. Immune checkpoint inhibitors provide sustained benefit in about 50% of MCC patients with advanced disease. Glypican-3 (GPC3) is an oncofetal tumor antigen that is an attractive target for chimeric antigen recepto...
Merkel cell carcinoma (MCC) is a rare and highly aggressive skin cancer with frequent viral etiology. Indeed, in about 80% of cases, there is an association with Merkel cell polyomavirus (MCPyV); the expression of viral T antigens is crucial for growth of virus-positive tumor cells. Since artesunate—a drug used to treat malaria—has been reported to...
Citations
... SLNB is a widely used method for pathologic staging as the guide for possible further radical lymphadenectomy [4]. Although extensive MCC metastases in a lymph node are easily detected in hematoxylin and eosin (HE) stained sections, single cells and small foci of micrometastatic MCC are exceedingly difficult to identify in the background of lymphoid cells. ...
Histopathological evaluation of lymph nodes in Merkel cell carcinoma has become crucial in progression estimation and treatment modification. This study was undertaken to determine the most sensitive immunohistochemical panel for detecting MCC nodal metastases. We included 56 patients with 102 metastatic MCC lymph nodes, which were tested with seven antibodies: cytokeratin (CKAE1/AE3), CK20, chromogranin A, synaptophysin, INSM1, SATB2, and neurofilament (NF). Tissue microarrays (TMA) composed of 2-mm tissue cores from each nodal metastasis were constructed. A semiquantitative 5-tier scoring system (0%, < 25%, 25–74%, 75–99%, 100% positive MCC cells with moderate to strong reactivity) was implemented. In the statistical assessment, we included Merkel cell polyomavirus (MCPyV) status and expression heterogeneity between lymph nodes from one patient. A cumulative percentage of moderate to strong expression ≥ 75% of tumoral cells was observed for single cell markers as follows: 91/102 (89.2%) SATB2, 85/102 (83%) CKAE1/AE3, 80/102 (78.4%) synaptophysin, 75/102 (75.5%) INSM1, 68/102 (66.7%) chromogranin A, 60/102 cases (58.8%) CK20, and 0/102 (0%) NF. Three markers presented a complete lack of immunoreactivity: 8/102 (7.8%) CK20, 7/102 (6.9%) chromogranin A, and 6/102 (5.9%) NF. All markers showed expression heterogeneity in lymph nodes from one patient; however, the most homogenous was INSM1. The probability of detecting nodal MCC metastases was the highest while using SATB2 as a first-line marker (89.2%) with subsequential adding CKAE1/AE3 (99%); these results were independent of MCPyV status. Synaptophysin showed a superior significance in confirming the neuroendocrine origin of metastatic cells. This comprehensive analysis allows us to recommend simultaneous evaluation of SATB2, CKAE1/AE3, and synaptophysin in the routine pathologic MCC lymph node protocol.
... The MCs are found deep in the epidermis of the top layer of the skin as innervated clusters of cells close to the nerve endings receiving touch and pressure sensations (6). The MCC is considered the second deadliest form of skin cancer after malignant melanoma, with a mortality rate of 35% (7). Skin cancer ranks as the 17th most prevalent cancer globally and one of the most diagnosed cancers worldwide. ...
Merkel cell carcinoma (MCC) is a rare neuroendocrine skin malignancy caused by human Merkel cell polyomavirus (MCV), leading to the most aggressive skin cancer in humans. MCV has been identified in approximately 43%–100% of MCC cases, contributing to the highly aggressive nature of primary cutaneous carcinoma and leading to a notable mortality rate. Currently, no existing vaccines or drug candidates have shown efficacy in addressing the ailment caused by this specific pathogen. Therefore, this study aimed to design a novel multiepitope vaccine candidate against the virus using integrated immunoinformatics and vaccinomics approaches. Initially, the highest antigenic, immunogenic, and non-allergenic epitopes of cytotoxic T lymphocytes, helper T lymphocytes, and linear B lymphocytes corresponding to the virus whole protein sequences were identified and retrieved for vaccine construction. Subsequently, the selected epitopes were linked with appropriate linkers and added an adjuvant in front of the construct to enhance the immunogenicity of the vaccine candidates. Additionally, molecular docking and dynamics simulations identified strong and stable binding interactions between vaccine candidates and human Toll-like receptor 4. Furthermore, computer-aided immune simulation found the real-life-like immune response of vaccine candidates upon administration to the human body. Finally, codon optimization was conducted on the vaccine candidates to facilitate the in silico cloning of the vaccine into the pET28+(a) cloning vector. In conclusion, the vaccine candidate developed in this study is anticipated to augment the immune response in humans and effectively combat the virus. Nevertheless, it is imperative to conduct in vitro and in vivo assays to evaluate the efficacy of these vaccine candidates thoroughly. These evaluations will provide critical insights into the vaccine’s effectiveness and potential for further development.
... UVR is therefore considered part of its etiology. The recently described Merkel Cell polyomavirus is believed to be a major cause of MCC [1,2,5,6,18], along with UVR-induced DNA damage [4,14,15,19,20]. MCC also occurs in immunocompromised individuals who are Merkel-Cell-polyomavirus negative [5,20], suggesting that multiple mechanisms are involved in its etiology. ...
... CMM and MCC do not have symptoms like non-skin cancers such as pain. MCC typically presents as a solitary, painless pink nodule on sun-exposed skin [1][2][3]. MCC is an aggressive skin cancer with high mortality [1][2][3][4][5][6]. Mucosal melanomas (MMs) arise in the mucosal epithelium and are very rare [7][8][9]. ...
... MCC typically presents as a solitary, painless pink nodule on sun-exposed skin [1][2][3]. MCC is an aggressive skin cancer with high mortality [1][2][3][4][5][6]. Mucosal melanomas (MMs) arise in the mucosal epithelium and are very rare [7][8][9]. ...
Little is known about the epidemiology of Merkel cell carcinoma (MCC) and mucosal melanoma (MM). Using the United States (US) National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program data, we compared MCC and MM with cutaneous malignant melanoma (CMM) with respect to incidence rates and prognostic factors to better understand disease etiologies. We describe the proportional incidences of the three cancers along with their survival rates based on 20 years of national data. The incidence rates in 2000–2019 were 203.7 per 1,000,000 people for CMM, 5.9 per 1,000,000 people for MCC and 0.1 per 1,000,000 people for MM. The rates of these cancers increased over time, with the rate of MM tripling between 2000–2009 and 2010–2019. The incidences of these cancers increased with age and rates were highest among non-Hispanic Whites. Fewer MCCs and MMS were diagnosed at the local stage compared with CMM. The cases in the 22 SEER registries in California were not proportional to the 2020 population census but instead were higher than expected for CMM and MCC and lower than expected for MM. Conversely, MM rates were higher than expected in Texas and New York. These analyses highlight similarities in the incidence rates of CMM and MCC—and differences between them and MM rates—by state. Understanding more about MCC and MM is important because of their higher potential for late diagnosis and metastasis, which lead to poor survival.
... The most important predictor for survival is lack of involvement of regional lymph nodes. 5 Other factors associated with poor prognosis include lymphovascular invasion (twofold increase of mortality), p63 expression, and immunosuppression. 5 ...
Merkel cell carcinoma (MCC) of the conjunctiva is rare. We report the case of a 73-year-old man who presented with unilateral foreign body sensation and blurred vision. A rapidly enlarging conjunctival lesion was identified and excised. The histopathological diagnosis was poorly differentiated squamous cell carcinoma, later reclassified as neuroendocrine / Merkel cell carcinoma following excision on subsequent recurrence. The patient developed lymph node and widespread metastatic disease. The challenges of diagnosing MCC at this site are discussed and the literature on treatment options for this aggressive disease is reviewed.
... These staging systems are often used for research purposes leading to inconsistency in the significance of parotid involvement in staging. Examples of commonly used staging systems include the Brigham and Women's system [54] , Clark's N1S3 system [55] , O'Brien's parotid and neck node system [56] , and the Immunosuppression, Treatment, Extranodal spread, and Margin status prognostic score [57] . ...
The management of non-melanoma skin cancers metastatic to the neck is challenging due to variability in biological behavior and patterns of regional lymphatic spread. Metastatic non-melanoma skin cancers to the parotid and neck often behave aggressively, with a high incidence of local recurrence after treatment and reduced five-year survival outcomes. Patterns of lymphatic spread are different from those seen in mucosal squamous cell carcinoma, with higher prevalence of disease in the parotid and superficial lymphatics. These factors require that treatment is individualized to achieve optimal outcomes. Traditionally, the management of non-melanoma skin cancers metastatic to lymph nodes has involved surgical excision followed by adjuvant radiation therapy. However, novel systemic therapies are showing promising results and their role in the management of these cancers is evolving
... Recent MCC coding expansion may have driven the increased accuracy of epidemiological studies, incorporating data from population-based registries. 16 Comparison between countries may be unreliable because different studies use different measures What's already known about this topic? � Merkel cell carcinoma (MCC) is a rare neuroendocrine carcinoma. ...
Merkel cell carcinoma (MCC) is a rare neuroendocrine carcinoma. The cellular origin of MCC may include Merkel cell precursors. The incidence of MCC has increased significantly however trends may have been confounded by evolving diagnostic criteria. The two key aetiologies of MCC are ultraviolet radiation and Merkel cell polyoma virus (MCPyV). Both have unique mechanisms of carcinogenesis. MCC presents non‐specifically as a rapidly growing, red‐to‐violet nodule on sun‐exposed areas. Diagnostic accuracy has improved through immunohistochemical markers such as CK‐20. Lymph nodes should be evaluated in MCC through examination and sentinel biopsy. USS, CT, MRI and CT‐PET may be useful in staging. Management depends on tumour location, stage and comorbidities. MCPyV status may guide treatment strategy in the future. Treatment for the primary MCC is commonly wide local excision followed by radiotherapy, guided by anatomical constraints. There is uncertainty about surgical margins. Treatments for nodal disease have not been determined through trials. They include nodal dissection or radiotherapy for clinically or radiologically apparent disease, and adjuvant nodal irradiation for negative nodes, microscopic disease or following nodal dissection for definite disease. Patients with loco‐regional advanced inoperable disease should be considered for combination therapy including chemotherapy, radiotherapy, surgery and immunotherapy. Systemic therapy for advanced disease includes immune checkpoint inhibitors targeting the PD‐1/PD‐L1 pathway. Avelumab can improve survival in metastatic MCC. Immunotherapy may result in longer disease control. Various other immunotherapeutic and molecular agents are undergoing trials. MCC continues to have a high mortality characterized by high recurrence and early metastases.
... In the eighth edition AJCC staging system, patients with stage pIII disease with no identifiable primary or an unknown primary are included in the stage pIIIA subgroup because they have a significantly better prognosis than patients with nodal disease and a known primary (stage pIIIB) (9). This may be because improved antitumor immunity eliminated the primary tumor and also targets residual disease (18). ...
... Thus, imaging is important to establish a diagnosis of this rare manifestation (Fig 11). 18 F-FDG PET is increasingly used for detection of distant metastasis. MCC is a hypermetabolic tumor with a reported SUV max (maximum standardized uptake value) for distant metastasis of 7.2-11.5 (26,27). ...
... A decrease in the extent or intensity of FDG activity in the face of increasing sclerosis at CT usually heralds healing (50). 18 F-FDG PET/CT is a good modality for staging and is increasingly used, as MCC is usually very FDG avid (Figs 11, 13). According to a large meta-analysis of 10 studies comprising 328 MCC patients who underwent 549 18 F-FDG PET/CT scans, 18 F-FDG PET/CT has sensitivity of 90% and specificity of 98%, allowing pathologic and nonpathologic reference standards (ie, use of clinical or radiologic follow-up as a standard) (51). ...
Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous neuroendocrine tumor with a higher mortality rate than melanoma. Approximately 40% of MCC patients have nodal or distant metastasis at initial presentation, and one-third of patients will develop distant metastatic disease over their clinical course. Although MCC is rare, its incidence has been steadily increasing. Furthermore, the immunogenicity of MCC and its diagnostic and therapeutic application have made MCC one of the most rapidly developing topics in dermatology and oncology. Owing to the aggressive and complex nature of MCC, a multidisciplinary approach is necessary for management of this tumor, including dermatologists, surgeons, radiation oncologists, medical oncologists, pathologists, radiologists, and nuclear medicine physicians. Imaging plays a crucial role in diagnosis, planning for surgery or radiation therapy, and assessment of treatment response and surveillance. However, MCC is still not well recognized among radiologists and nuclear medicine physicians, likely owing to its rarity. The purpose of this review is to raise awareness of MCC among imaging experts by describing the epidemiology, pathophysiology, and clinical features of MCC and current clinical management with a focus on the role of imaging. The authors highlight imaging findings characteristic of MCC, as well as the clinical significance of CT, MRI, sentinel lymph node mapping, fluorine 18 fluorodeoxyglucose PET/CT, and other nuclear medicine studies such as bone scintigraphy and somatostatin receptor scintigraphy. ©RSNA, 2019.
... Early recognition of MCC is important since the expected 5 years survival is 79% in the early stage (IA), unfortunately only 18% by the time of metastasis (stage IV). High clinical suspicion and early diagnosis may improve survival rates 10 . Due to its rarity epidemiological data are scarce, and have not been previously analyzed in Turkey to identify the main epidemiological trends. ...
Background:
There is limited data knowledge of Merkel cell carcinoma (MCC) in Turkey aside from a few case reports.
Objective:
The aim of this study was to describe the clinical characteristics, demographic features, therapeutic parameters, and outcome of primary cutaneous MCC cases from Turkey.
Methods:
Digital medical records of the 13 MCC patients who were followed-up at a tertiary referral center were retrospectively analyzed. Clinic, demographic, tumor characteristics, and survival of the patients were retrieved.
Results:
Most of our patients were elderly. Female predominance was noticed. The most common primary site of the tumors was the lower extremities. The overall survival was 42 months, 68% at first year, 68% at third years, and 29% at fifth years.
Conclusion:
This is the first largest report from Turkish population with female predominance, and lower extremity tendency.
... For this reason, treatments that rely on different procedures and/or on agents other than drugs have been investigated, including radiation therapy [133,134]. Immunotherapy using a humanized anti-PD1 antibody (for example, systemic pembrolizumab (MK-3475)) [135] and targeted molecular therapy are two other investigational approaches that have been used to treat metastatic Merkel cell carcinoma [136][137][138][139]. The disease is rare; therapeutic response data often derive from case reports and studies of retrospective series rather than clinical trials, making it challenging to define the role of chemotherapy in the management of advanced Merkel cell carcinoma. ...
Skin cancer has always been and remains the leader among all tumors in terms of occurrence. One of the main factors responsible for skin cancer, natural and artificial UV radiation, causes the mutations that transform healthy cells into cancer cells. These mutations inactivate apoptosis, an event required to avoid the malignant transformation of healthy cells. Among these deadliest of cancers, melanoma and its 'younger sister', Merkel cell carcinoma, are the most lethal. The heavy toll of skin cancers stems from their rapid progression and the fact that they metastasize easily. Added to this is the difficulty in determining reliable margins when excising tumors and the lack of effective chemotherapy. Possibly the biggest problem posed by skin cancer is reliably detecting the extent to which cancer cells have spread throughout the body. The initial tumor is visible and can be removed, whereas metastases are invisible to the naked eye and much harder to eliminate. In our opinion, antisense oligonucleotides, which can be used in the form of targeted ointments, provide real hope as a treatment that will eliminate cancer cells near the tumor focus both before and after surgery.
... Historically, as many as five different staging systems have been utilized to stratify risk and prognosis for patients with MCC [78]. As for most other solid cancers, staging and prognosis of MCC depend largely on the extent of disease burden. ...
Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma. Incidence of MCC continues to rise, and risk factors include advanced age, pale skin, chronic sun exposure, and immune suppression. Diagnosing MCC utilizes a combination of morphology and immunohistochemistry. Merkel cell polyomavirus (MCPyV) is present in approximately 70–80% of MCCs and represents a key pathogenic driver in those MCCs. In contrast, MCPyV-negative MCCs arise through progressive accumulation of ultraviolet-light induced somatic mutations. Staging of MCC proceeds according to the American Joint Commission on Cancer (AJCC) 8th Edition, which utilizes features of the primary tumor together with regional lymph node(s) (clinically and/or pathologically detected) and/or distant metastases. Many potentially useful biomarkers have been studied to refine risk stratification in MCC. In recent years, the host immune infiltrate has been leveraged as immune checkpoint blockade has emerged as an efficacious mode of treatment for patients with advanced MCC.
