Merkel cell carcinoma (MCC) or trabecular cancer is a rare, malignant neuroendocrine skin tumor. Sun-exposed skin such as the head and neck area are most frequently affected, which develops as rapid, asymptomatic, solid, red-violaceous nodules.
UV exposure, immunosuppression, advancing age, and the development of Merkel cell polyomavirus (MCPyV) infection are specific risk factors.
Epidemiology
Over the past decades, the reported incidences have continuously increased, with an estimated 2000 newly diagnosed cases each year due to improved diagnostic procedures and an increase in the prevalence of known risk factors. Most patients are older males, and about 90% are Caucasian.
Anatomy
Pathophysiology
The cause of carcinogenesis is unknown. Infection of MCPyV is common in patients with malignancies, advanced age, chemotherapy, immunosuppressive drugs, and immuno-comprised conditions that lead to MCPyV tumorigenesis.
Specific mutations are required to integrate the virus in the host DNA and are hypothesized to be driven by environmental mutagens like UV radiation. These occurrences promote an asymptomatic viral infection to tumorigenic.
The remaining virus-negative tumors develop UV-signature mutations and have a significantly higher mutation burden than tumors that are MCPyV-positive. The residual tumors acquire UV signature mutations.
Etiology
The origin of Merkel cell carcinoma is either due to an epidermal or dermal stem cell rather than a developed Merkel cell. MCPyV is a polyomavirus that is a double-stranded unenveloped DNA virus. MCPyV infection has been found in almost 80% of the cases, implying its significance as an etiologic cause of carcinogenesis.
Infection in humans with the virus is widespread, usually asymptomatic, except in cases of Merkel cell carcinoma in which the viral DNA is clonally integrated into the host genome. UV exposure, aging, and immunosuppression are also considered risk factors.
Genetics
Prognostic Factors
Merkel cell carcinoma is a rare skin cancer with localized or regional metastatic development at diagnosis. The prognosis is poor and depends on the metastasis stage, with a five-year survival rate of 51% in local disease.
In patients with stage 1 and stage, 2 of the disease, a negative sentinel lymph node biopsy significantly predicts disease-free duration and survival rate. Factors associated with increased survival rate are tumors less than 2 cm in size, female gender, and located in the upper extremities.
Clinical History
Clinical History
Merkel cell carcinoma typically presents as a rapidly growing, solitary, cutaneous, or subcutaneous tumor. This cancer is usually located in sun-exposed areas, such as the head and neck, although it can also occur less frequently on the extremities and buttocks. The tumor usually arises in the skin; however, it has also been described in several extracutaneous sites such as the salivary glands and nasal cavity.
However, whether MCC caused by Merkel cell polyomavirus (MCPyV+) and MCC associated with ultraviolet (UV) exposure and not caused by MCPyV tend to occur at the same sites is not yet fully understood. Merkel cell carcinoma is often diagnosed in advanced stages due to its aggressive nature.
Only 65% of patients present with local disease, meaning that many cases are already in an advanced stage when diagnosed. One factor that further complicates the diagnosis and treatment of MCC is that it can arise in conjunction with other skin cancers, such as squamous cell carcinoma, basal cell carcinoma, or sebaceous carcinoma.
Physical Examination
Physical Examination
MCC is a rapidly growing and solitary cutaneous or subcutaneous tumor that is usually found on sun-exposed areas of the head, neck, extremities, and buttocks. It is usually asymptomatic, presenting as a red-to-violet nodule which can be misconstrued as a benign lesion or another type of malignancy. The lesions associated with MCC are often asymptomatic and appear as red-to-violet nodules, which can sometimes be mistaken for benign cysts or other malignant lesions, such as cutaneous squamous cell carcinoma, lymphoma, or metastasis.
Ulceration of the lesions is rare; in some cases, multiple lesions may arise at different body sites. Due to the nonspecific nature of the presentation, clinical diagnosis of MCC is often delayed. Therefore, the acronym AEIOU has been used to help recall relevant clinical features of MCC and the patient: asymptomatic, expanding rapidly, immunosuppressed, >50 years of age, and UV-exposed.
The most recent AJCC staging system, adopted in 2018, groups MCC into four categories based on the features at presentation: stage 0 (in situ), stage I with primary lesion, stage II with primary lesion >2 cm, stage III as nodal spread and stage IV in a metastatic disease beyond the local nodes. Most initial diagnoses are stage I or stage II MCC, with recurrences usually occurring within the first 2-3 years. Metastases are commonly found in the skin, distant lymph nodes, adrenal glands, lungs, liver, brain, and bones.
Age group
Associated comorbidity
Associated activity
Acuity of presentation
Differential Diagnoses
Differential Diagnosis
Basal Cell Carcinoma
Dermatofibroma
Cutaneous melanoma
Cutaneous squamous cell carcinoma
Keratocanthoma
Laboratory Studies
Imaging Studies
Procedures
Histologic Findings
Staging
Treatment Paradigm
When viable, Merkel cell carcinoma is treated with comprehensive local excision of the original tumor with margins of 1-2 cm to the advancing fascia of muscle or pericranium. If sentinel lymph node biopsy does not show any effect, Mohs micrographic surgical procedure may be an alternative (SLNB). Adjuvant radiation treatment to the main tumor site may be explored in low-risk individuals with a small primary tumor and no additional risk factors.
The value of adjuvant radiation in the SLNB-negative basin is debatable. However, it may be appropriate in circumstances where a false-negative SLNB is possible or in individuals with acute immunosuppression. In head and neck disorders, the chance of a false-negative SLNB is greater. Complete lymph node irradiation or nodal basin dissection is the preferred treatment for locoregional lymph node-limited Merkel cell cancer.
If particular NCCN criteria are met lymph node dissection is the initial treatment observed following postoperative irradiation in patients with clinically differentiated adenopathy. Patients with microscopic nodal illness on SLNB but no clinically palpable nodes or imaging evidence of nodal involvement should be evaluated for radiation alone. Adjuvant radiation is advised for individuals with more extensive illness encompassing multiple nodes and extracapsular extension as shown by lymph node dissection.
Delaying adjuvant radiation therapy should be avoided since it is related with poor outcomes. Immunotherapy and cytotoxic chemotherapy are the only systemic agents available, with immune-based treatments showing promising outcomes in clinical studies. In patients with MCC, avelumab, nivolumab, pembrolizumab, and anti-PD-1 and PD-L1 antibodies revealed a significant progression-free survival of nine months with pembrolizumab treatment.
Merkel cell carcinoma (MCC) or trabecular cancer is a rare, malignant neuroendocrine skin tumor. Sun-exposed skin such as the head and neck area are most frequently affected, which develops as rapid, asymptomatic, solid, red-violaceous nodules.
UV exposure, immunosuppression, advancing age, and the development of Merkel cell polyomavirus (MCPyV) infection are specific risk factors.
Over the past decades, the reported incidences have continuously increased, with an estimated 2000 newly diagnosed cases each year due to improved diagnostic procedures and an increase in the prevalence of known risk factors. Most patients are older males, and about 90% are Caucasian.
The cause of carcinogenesis is unknown. Infection of MCPyV is common in patients with malignancies, advanced age, chemotherapy, immunosuppressive drugs, and immuno-comprised conditions that lead to MCPyV tumorigenesis.
Specific mutations are required to integrate the virus in the host DNA and are hypothesized to be driven by environmental mutagens like UV radiation. These occurrences promote an asymptomatic viral infection to tumorigenic.
The remaining virus-negative tumors develop UV-signature mutations and have a significantly higher mutation burden than tumors that are MCPyV-positive. The residual tumors acquire UV signature mutations.
The origin of Merkel cell carcinoma is either due to an epidermal or dermal stem cell rather than a developed Merkel cell. MCPyV is a polyomavirus that is a double-stranded unenveloped DNA virus. MCPyV infection has been found in almost 80% of the cases, implying its significance as an etiologic cause of carcinogenesis.
Infection in humans with the virus is widespread, usually asymptomatic, except in cases of Merkel cell carcinoma in which the viral DNA is clonally integrated into the host genome. UV exposure, aging, and immunosuppression are also considered risk factors.
Merkel cell carcinoma is a rare skin cancer with localized or regional metastatic development at diagnosis. The prognosis is poor and depends on the metastasis stage, with a five-year survival rate of 51% in local disease.
In patients with stage 1 and stage, 2 of the disease, a negative sentinel lymph node biopsy significantly predicts disease-free duration and survival rate. Factors associated with increased survival rate are tumors less than 2 cm in size, female gender, and located in the upper extremities.
Clinical History
Merkel cell carcinoma typically presents as a rapidly growing, solitary, cutaneous, or subcutaneous tumor. This cancer is usually located in sun-exposed areas, such as the head and neck, although it can also occur less frequently on the extremities and buttocks. The tumor usually arises in the skin; however, it has also been described in several extracutaneous sites such as the salivary glands and nasal cavity.
However, whether MCC caused by Merkel cell polyomavirus (MCPyV+) and MCC associated with ultraviolet (UV) exposure and not caused by MCPyV tend to occur at the same sites is not yet fully understood. Merkel cell carcinoma is often diagnosed in advanced stages due to its aggressive nature.
Only 65% of patients present with local disease, meaning that many cases are already in an advanced stage when diagnosed. One factor that further complicates the diagnosis and treatment of MCC is that it can arise in conjunction with other skin cancers, such as squamous cell carcinoma, basal cell carcinoma, or sebaceous carcinoma.
Physical Examination
MCC is a rapidly growing and solitary cutaneous or subcutaneous tumor that is usually found on sun-exposed areas of the head, neck, extremities, and buttocks. It is usually asymptomatic, presenting as a red-to-violet nodule which can be misconstrued as a benign lesion or another type of malignancy. The lesions associated with MCC are often asymptomatic and appear as red-to-violet nodules, which can sometimes be mistaken for benign cysts or other malignant lesions, such as cutaneous squamous cell carcinoma, lymphoma, or metastasis.
Ulceration of the lesions is rare; in some cases, multiple lesions may arise at different body sites. Due to the nonspecific nature of the presentation, clinical diagnosis of MCC is often delayed. Therefore, the acronym AEIOU has been used to help recall relevant clinical features of MCC and the patient: asymptomatic, expanding rapidly, immunosuppressed, >50 years of age, and UV-exposed.
The most recent AJCC staging system, adopted in 2018, groups MCC into four categories based on the features at presentation: stage 0 (in situ), stage I with primary lesion, stage II with primary lesion >2 cm, stage III as nodal spread and stage IV in a metastatic disease beyond the local nodes. Most initial diagnoses are stage I or stage II MCC, with recurrences usually occurring within the first 2-3 years. Metastases are commonly found in the skin, distant lymph nodes, adrenal glands, lungs, liver, brain, and bones.
Differential Diagnosis
Basal Cell Carcinoma
Dermatofibroma
Cutaneous melanoma
Cutaneous squamous cell carcinoma
Keratocanthoma
When viable, Merkel cell carcinoma is treated with comprehensive local excision of the original tumor with margins of 1-2 cm to the advancing fascia of muscle or pericranium. If sentinel lymph node biopsy does not show any effect, Mohs micrographic surgical procedure may be an alternative (SLNB). Adjuvant radiation treatment to the main tumor site may be explored in low-risk individuals with a small primary tumor and no additional risk factors.
The value of adjuvant radiation in the SLNB-negative basin is debatable. However, it may be appropriate in circumstances where a false-negative SLNB is possible or in individuals with acute immunosuppression. In head and neck disorders, the chance of a false-negative SLNB is greater. Complete lymph node irradiation or nodal basin dissection is the preferred treatment for locoregional lymph node-limited Merkel cell cancer.
If particular NCCN criteria are met lymph node dissection is the initial treatment observed following postoperative irradiation in patients with clinically differentiated adenopathy. Patients with microscopic nodal illness on SLNB but no clinically palpable nodes or imaging evidence of nodal involvement should be evaluated for radiation alone. Adjuvant radiation is advised for individuals with more extensive illness encompassing multiple nodes and extracapsular extension as shown by lymph node dissection.
Delaying adjuvant radiation therapy should be avoided since it is related with poor outcomes. Immunotherapy and cytotoxic chemotherapy are the only systemic agents available, with immune-based treatments showing promising outcomes in clinical studies. In patients with MCC, avelumab, nivolumab, pembrolizumab, and anti-PD-1 and PD-L1 antibodies revealed a significant progression-free survival of nine months with pembrolizumab treatment.
For >12 years
800 mg given IV over 1hr every 2-weeks
the duration of the therapy continues until disease progression, or unacceptable toxicity occurs
https://www.ncbi.nlm.nih.gov/books/NBK482329/
medtigo
Merkel Cell Carcinoma
Updated :
August 17, 2023
Merkel cell carcinoma (MCC) or trabecular cancer is a rare, malignant neuroendocrine skin tumor. Sun-exposed skin such as the head and neck area are most frequently affected, which develops as rapid, asymptomatic, solid, red-violaceous nodules.
UV exposure, immunosuppression, advancing age, and the development of Merkel cell polyomavirus (MCPyV) infection are specific risk factors.
Over the past decades, the reported incidences have continuously increased, with an estimated 2000 newly diagnosed cases each year due to improved diagnostic procedures and an increase in the prevalence of known risk factors. Most patients are older males, and about 90% are Caucasian.
The cause of carcinogenesis is unknown. Infection of MCPyV is common in patients with malignancies, advanced age, chemotherapy, immunosuppressive drugs, and immuno-comprised conditions that lead to MCPyV tumorigenesis.
Specific mutations are required to integrate the virus in the host DNA and are hypothesized to be driven by environmental mutagens like UV radiation. These occurrences promote an asymptomatic viral infection to tumorigenic.
The remaining virus-negative tumors develop UV-signature mutations and have a significantly higher mutation burden than tumors that are MCPyV-positive. The residual tumors acquire UV signature mutations.
The origin of Merkel cell carcinoma is either due to an epidermal or dermal stem cell rather than a developed Merkel cell. MCPyV is a polyomavirus that is a double-stranded unenveloped DNA virus. MCPyV infection has been found in almost 80% of the cases, implying its significance as an etiologic cause of carcinogenesis.
Infection in humans with the virus is widespread, usually asymptomatic, except in cases of Merkel cell carcinoma in which the viral DNA is clonally integrated into the host genome. UV exposure, aging, and immunosuppression are also considered risk factors.
Merkel cell carcinoma is a rare skin cancer with localized or regional metastatic development at diagnosis. The prognosis is poor and depends on the metastasis stage, with a five-year survival rate of 51% in local disease.
In patients with stage 1 and stage, 2 of the disease, a negative sentinel lymph node biopsy significantly predicts disease-free duration and survival rate. Factors associated with increased survival rate are tumors less than 2 cm in size, female gender, and located in the upper extremities.
Clinical History
Merkel cell carcinoma typically presents as a rapidly growing, solitary, cutaneous, or subcutaneous tumor. This cancer is usually located in sun-exposed areas, such as the head and neck, although it can also occur less frequently on the extremities and buttocks. The tumor usually arises in the skin; however, it has also been described in several extracutaneous sites such as the salivary glands and nasal cavity.
However, whether MCC caused by Merkel cell polyomavirus (MCPyV+) and MCC associated with ultraviolet (UV) exposure and not caused by MCPyV tend to occur at the same sites is not yet fully understood. Merkel cell carcinoma is often diagnosed in advanced stages due to its aggressive nature.
Only 65% of patients present with local disease, meaning that many cases are already in an advanced stage when diagnosed. One factor that further complicates the diagnosis and treatment of MCC is that it can arise in conjunction with other skin cancers, such as squamous cell carcinoma, basal cell carcinoma, or sebaceous carcinoma.
Physical Examination
MCC is a rapidly growing and solitary cutaneous or subcutaneous tumor that is usually found on sun-exposed areas of the head, neck, extremities, and buttocks. It is usually asymptomatic, presenting as a red-to-violet nodule which can be misconstrued as a benign lesion or another type of malignancy. The lesions associated with MCC are often asymptomatic and appear as red-to-violet nodules, which can sometimes be mistaken for benign cysts or other malignant lesions, such as cutaneous squamous cell carcinoma, lymphoma, or metastasis.
Ulceration of the lesions is rare; in some cases, multiple lesions may arise at different body sites. Due to the nonspecific nature of the presentation, clinical diagnosis of MCC is often delayed. Therefore, the acronym AEIOU has been used to help recall relevant clinical features of MCC and the patient: asymptomatic, expanding rapidly, immunosuppressed, >50 years of age, and UV-exposed.
The most recent AJCC staging system, adopted in 2018, groups MCC into four categories based on the features at presentation: stage 0 (in situ), stage I with primary lesion, stage II with primary lesion >2 cm, stage III as nodal spread and stage IV in a metastatic disease beyond the local nodes. Most initial diagnoses are stage I or stage II MCC, with recurrences usually occurring within the first 2-3 years. Metastases are commonly found in the skin, distant lymph nodes, adrenal glands, lungs, liver, brain, and bones.
Differential Diagnosis
Basal Cell Carcinoma
Dermatofibroma
Cutaneous melanoma
Cutaneous squamous cell carcinoma
Keratocanthoma
When viable, Merkel cell carcinoma is treated with comprehensive local excision of the original tumor with margins of 1-2 cm to the advancing fascia of muscle or pericranium. If sentinel lymph node biopsy does not show any effect, Mohs micrographic surgical procedure may be an alternative (SLNB). Adjuvant radiation treatment to the main tumor site may be explored in low-risk individuals with a small primary tumor and no additional risk factors.
The value of adjuvant radiation in the SLNB-negative basin is debatable. However, it may be appropriate in circumstances where a false-negative SLNB is possible or in individuals with acute immunosuppression. In head and neck disorders, the chance of a false-negative SLNB is greater. Complete lymph node irradiation or nodal basin dissection is the preferred treatment for locoregional lymph node-limited Merkel cell cancer.
If particular NCCN criteria are met lymph node dissection is the initial treatment observed following postoperative irradiation in patients with clinically differentiated adenopathy. Patients with microscopic nodal illness on SLNB but no clinically palpable nodes or imaging evidence of nodal involvement should be evaluated for radiation alone. Adjuvant radiation is advised for individuals with more extensive illness encompassing multiple nodes and extracapsular extension as shown by lymph node dissection.
Delaying adjuvant radiation therapy should be avoided since it is related with poor outcomes. Immunotherapy and cytotoxic chemotherapy are the only systemic agents available, with immune-based treatments showing promising outcomes in clinical studies. In patients with MCC, avelumab, nivolumab, pembrolizumab, and anti-PD-1 and PD-L1 antibodies revealed a significant progression-free survival of nine months with pembrolizumab treatment.
https://www.ncbi.nlm.nih.gov/books/NBK482329/
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