New Merkel Cell Staging Emphasizes Pathological Node Evaluation

Sentinel lymph node biopsy is an important but greatly underused tool for staging and prognosis of Merkel cell carcinoma, according a recent multicenter analysis of 5,823 cases of the aggressive skin cancer.

This massive study led to the first consensus staging system for Merkel cell carcinoma. The new system replaces five conflicting staging systems published in the last 17 years, none of which were based upon more than 251 cases.

"The situation was a complete mess. If a person said, 'stage III Merkel cell carcinoma,' you didn’t know if they were talking about a deep primary, nodal disease, or distant metastatic disease," recalled Dr. Paul Nghiem, senior author of the analysis and new staging system.

The crucial difference between the new staging system and the prior ones lies in its emphasis on determining the pathological status of the nodes, according to Dr. Nghiem, a dermatologist at the University of Washington, Seattle.

Prior studies had established that roughly one-third of patients with clinically node-negative Merkel cell carcinoma (MCC) have microscopic nodal disease. Yet pathological nodal evaluation hasn’t been the norm; indeed, it wasn’t performed in more than two-thirds of the 5,823 cases of MCC obtained from the prospective National Cancer Data Base, which served as the basis for the new staging system.

Dr. Nghiem and his coworkers demonstrated that pathological nodal evaluation is a clinically important unused resource. For example, 5-year relative survival was 79% in patients with Stage IA disease under the new system, defined as local disease not more than 2 cm in diameter and with negative lymph nodes by pathological exam.

In contrast, survival in stage IB patients – local disease not greater than 2 cm, but with nodes that were negative only by clinical evaluation – was only 60%. The same pattern was seen in stage II and III disease under the new system.

Pathological lymph node evaluation not only results in more accurate staging and determination of prognosis, it also has important therapeutic implications.

"If the biopsy is positive, nodal treatment reduces recurrences in that nodal bed," Dr. Nghiem said.

He and his coworkers have shown that lymph node adjuvant radiation therapy and completion lymphadenectomy are similarly highly effective therapies for both microscopic and palpable lymph node involvement (Cancer 2010;116:1783-90). So treatment of the node bed in sentinel lymph node-positive disease should be either radiotherapy or surgery, but not both. It doesn’t make sense to subject patients to the added side effects of dual therapy when either therapy alone is so effective, he continued.

The only circumstances in which he and his colleagues don’t perform sentinel lymph node biopsy in MCC are when they’re planning to do radiation therapy anyway, if prognostic data simply aren’t important to the patient, or when the tumor is in the parotid region where for technical reasons the false-negative rate is substantial.

The best local therapy for MCC is excision with or without adjuvant radiation therapy. The only conditions in which adjuvant radiotherapy can be dispensed with are when a patient has all of five features signaling a low risk for local recurrence: negative sentinel lymph node biopsy, a primary tumor 1 cm or less in diameter, pathologically negative surgical margins, no lymphovascular invasion in the primary tumor, and no profoundly immunosuppressive comorbid conditions. If all five of those features are met, the risk of recurrence is probably less than 10% and may not justify the down sides of radiation, according to Dr. Nghiem.

The immunosuppressive conditions that are particularly problematic include chronic lymphocytic leukemia, which has been associated with a 30- to 50-fold increased risk of MCC; being a solid organ transplant recipient, which carries a 10-fold risk; and HIV positive status, which has been reported to increase the risk of MCC 13-fold.

It’s typically necessary to ask the pathologist if lymphovascular invasion is present in the primary tumor, as this is information not usually included in the report, the dermatologist explained at the 35th annual Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation.

Development of the new MCC consensus staging system (J. Am. Acad. Dermatol. 2010;63:751-61) was supported by the National Institutes of Health and American Cancer Society. Dr. Nghiem declared having no financial conflicts. Skin Disease Education Foundation and this news organization are owned by Elsevier.

Sentinel lymph node biopsy is an important but greatly underused tool for staging and prognosis of Merkel cell carcinoma, according a recent multicenter analysis of 5,823 cases of the aggressive skin cancer.

This massive study led to the first consensus staging system for Merkel cell carcinoma. The new system replaces five conflicting staging systems published in the last 17 years, none of which were based upon more than 251 cases.

"The situation was a complete mess. If a person said, 'stage III Merkel cell carcinoma,' you didn’t know if they were talking about a deep primary, nodal disease, or distant metastatic disease," recalled Dr. Paul Nghiem, senior author of the analysis and new staging system.

The crucial difference between the new staging system and the prior ones lies in its emphasis on determining the pathological status of the nodes, according to Dr. Nghiem, a dermatologist at the University of Washington, Seattle.

Prior studies had established that roughly one-third of patients with clinically node-negative Merkel cell carcinoma (MCC) have microscopic nodal disease. Yet pathological nodal evaluation hasn’t been the norm; indeed, it wasn’t performed in more than two-thirds of the 5,823 cases of MCC obtained from the prospective National Cancer Data Base, which served as the basis for the new staging system.

Dr. Nghiem and his coworkers demonstrated that pathological nodal evaluation is a clinically important unused resource. For example, 5-year relative survival was 79% in patients with Stage IA disease under the new system, defined as local disease not more than 2 cm in diameter and with negative lymph nodes by pathological exam.

In contrast, survival in stage IB patients – local disease not greater than 2 cm, but with nodes that were negative only by clinical evaluation – was only 60%. The same pattern was seen in stage II and III disease under the new system.

Pathological lymph node evaluation not only results in more accurate staging and determination of prognosis, it also has important therapeutic implications.

"If the biopsy is positive, nodal treatment reduces recurrences in that nodal bed," Dr. Nghiem said.

He and his coworkers have shown that lymph node adjuvant radiation therapy and completion lymphadenectomy are similarly highly effective therapies for both microscopic and palpable lymph node involvement (Cancer 2010;116:1783-90). So treatment of the node bed in sentinel lymph node-positive disease should be either radiotherapy or surgery, but not both. It doesn’t make sense to subject patients to the added side effects of dual therapy when either therapy alone is so effective, he continued.

The only circumstances in which he and his colleagues don’t perform sentinel lymph node biopsy in MCC are when they’re planning to do radiation therapy anyway, if prognostic data simply aren’t important to the patient, or when the tumor is in the parotid region where for technical reasons the false-negative rate is substantial.

The best local therapy for MCC is excision with or without adjuvant radiation therapy. The only conditions in which adjuvant radiotherapy can be dispensed with are when a patient has all of five features signaling a low risk for local recurrence: negative sentinel lymph node biopsy, a primary tumor 1 cm or less in diameter, pathologically negative surgical margins, no lymphovascular invasion in the primary tumor, and no profoundly immunosuppressive comorbid conditions. If all five of those features are met, the risk of recurrence is probably less than 10% and may not justify the down sides of radiation, according to Dr. Nghiem.

The immunosuppressive conditions that are particularly problematic include chronic lymphocytic leukemia, which has been associated with a 30- to 50-fold increased risk of MCC; being a solid organ transplant recipient, which carries a 10-fold risk; and HIV positive status, which has been reported to increase the risk of MCC 13-fold.

It’s typically necessary to ask the pathologist if lymphovascular invasion is present in the primary tumor, as this is information not usually included in the report, the dermatologist explained at the 35th annual Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation.

Development of the new MCC consensus staging system (J. Am. Acad. Dermatol. 2010;63:751-61) was supported by the National Institutes of Health and American Cancer Society. Dr. Nghiem declared having no financial conflicts. Skin Disease Education Foundation and this news organization are owned by Elsevier.

Sentinel lymph node biopsy is an important but greatly underused tool for staging and prognosis of Merkel cell carcinoma, according a recent multicenter analysis of 5,823 cases of the aggressive skin cancer.

This massive study led to the first consensus staging system for Merkel cell carcinoma. The new system replaces five conflicting staging systems published in the last 17 years, none of which were based upon more than 251 cases.

"The situation was a complete mess. If a person said, 'stage III Merkel cell carcinoma,' you didn’t know if they were talking about a deep primary, nodal disease, or distant metastatic disease," recalled Dr. Paul Nghiem, senior author of the analysis and new staging system.

The crucial difference between the new staging system and the prior ones lies in its emphasis on determining the pathological status of the nodes, according to Dr. Nghiem, a dermatologist at the University of Washington, Seattle.

Prior studies had established that roughly one-third of patients with clinically node-negative Merkel cell carcinoma (MCC) have microscopic nodal disease. Yet pathological nodal evaluation hasn’t been the norm; indeed, it wasn’t performed in more than two-thirds of the 5,823 cases of MCC obtained from the prospective National Cancer Data Base, which served as the basis for the new staging system.

Dr. Nghiem and his coworkers demonstrated that pathological nodal evaluation is a clinically important unused resource. For example, 5-year relative survival was 79% in patients with Stage IA disease under the new system, defined as local disease not more than 2 cm in diameter and with negative lymph nodes by pathological exam.

In contrast, survival in stage IB patients – local disease not greater than 2 cm, but with nodes that were negative only by clinical evaluation – was only 60%. The same pattern was seen in stage II and III disease under the new system.

Pathological lymph node evaluation not only results in more accurate staging and determination of prognosis, it also has important therapeutic implications.

"If the biopsy is positive, nodal treatment reduces recurrences in that nodal bed," Dr. Nghiem said.

He and his coworkers have shown that lymph node adjuvant radiation therapy and completion lymphadenectomy are similarly highly effective therapies for both microscopic and palpable lymph node involvement (Cancer 2010;116:1783-90). So treatment of the node bed in sentinel lymph node-positive disease should be either radiotherapy or surgery, but not both. It doesn’t make sense to subject patients to the added side effects of dual therapy when either therapy alone is so effective, he continued.

The only circumstances in which he and his colleagues don’t perform sentinel lymph node biopsy in MCC are when they’re planning to do radiation therapy anyway, if prognostic data simply aren’t important to the patient, or when the tumor is in the parotid region where for technical reasons the false-negative rate is substantial.

The best local therapy for MCC is excision with or without adjuvant radiation therapy. The only conditions in which adjuvant radiotherapy can be dispensed with are when a patient has all of five features signaling a low risk for local recurrence: negative sentinel lymph node biopsy, a primary tumor 1 cm or less in diameter, pathologically negative surgical margins, no lymphovascular invasion in the primary tumor, and no profoundly immunosuppressive comorbid conditions. If all five of those features are met, the risk of recurrence is probably less than 10% and may not justify the down sides of radiation, according to Dr. Nghiem.

The immunosuppressive conditions that are particularly problematic include chronic lymphocytic leukemia, which has been associated with a 30- to 50-fold increased risk of MCC; being a solid organ transplant recipient, which carries a 10-fold risk; and HIV positive status, which has been reported to increase the risk of MCC 13-fold.

It’s typically necessary to ask the pathologist if lymphovascular invasion is present in the primary tumor, as this is information not usually included in the report, the dermatologist explained at the 35th annual Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation.

Development of the new MCC consensus staging system (J. Am. Acad. Dermatol. 2010;63:751-61) was supported by the National Institutes of Health and American Cancer Society. Dr. Nghiem declared having no financial conflicts. Skin Disease Education Foundation and this news organization are owned by Elsevier.