AEIOU May Help Make Merkel Cell Diagnosis

PORTLAND, ORE. — Skin lesions are a hallmark of Merkel cell carcinoma, yet dermatologists often find themselves out of the loop in diagnosing patients with the disease, said Dr. Paul Nghiem.

"These [lesions] are typically biopsied as a cyst and the patient usually has to argue for one, two, or three doctor's visits to have the lesion biopsied," Dr. Nghiem said at the annual meeting of the Pacific Dermatologic Association. "They're usually biopsied by a reluctant primary care physician who thinks they're taking off a cyst. Then they may be referred to medical oncology or to surgical oncology, but rarely to dermatology."

About 1,500 new cases of Merkel cell carcinoma (MCC) are diagnosed in the United States each year (J. Invest. Dermatol. 2007;127:2100-3), which is about the same incidence as cutaneous T-cell lymphoma or dermatofibrosarcoma protuberans, said Dr. Nghiem, an expert on the disease who is associate professor of dermatology, medicine, and pathology at the University of Washington, Seattle.

MCC is significantly more lethal than melanoma (40% vs. 15%, respectively), and its reported incidence has increased threefold since 1986 (J. Surg. Oncol. 2005;89:1-4).

"A big reason for that is that it's not missed as much," Dr. Nghiem said. "There are better tools for pathologists to use to make the diagnosis."

The three main risk factors for MCC are prolonged sun exposure, immune suppression, and age over 50 years. "Ninety-four percent of all MCC cases are in people aged 50 or older," he said. "There is a very strong synergy with age" (J. Am. Acad. Dermatol. 2008;58:375-81).

Dr. Nghiem said that HIV-positive patients had about a 13-fold increase of MCC in one study (Lancet 2002;359:497-8), while another study showed that solid organ transplant recipients have about a 10-fold increase (Transplantation 1999;68:1717-21).

He and his associates devised the acronym AEIOU to describe the clinical features of Merkel cell carcinoma based on an analysis of 195 patients given the diagnosis between 1980 and 2007 (J. Am. Acad. Dermatol. 2008; 58:375-81). The acronym stands for Asymptomatic, Expanding rapidly, Immune compromised, Older than 50, and UV-exposed, fair skin.

"Under no circumstances do I think that this is a highly specific test," said Dr. Nghiem, whose clinic is based at the Fred Hutchinson Cancer Research Center in Seattle. "It's not going to be up there with the ABCDs of melanoma, but if you see these characteristics together, you may want to think about doing a biopsy."

More than half of the lesions in the 195 patients evaluated (56%) were presumed to be benign at biopsy, and 32% presented on the head and neck, followed by the lower limb (30%), upper limb (20%), trunk (10%), and buttock (8%).

The majority of lesions (81%) presented on sun-exposed skin, but one in six was in a sun-protected site.

Nearly all of the lesions (88%) were asymptomatic ("neither tender nor itchy," he said), 63% doubled in size in the past 3 months, and 8% of the patients were profoundly immune suppressed. "That is a 16-fold increase over the normal population, but still a minority of all Merkel cell cases," he said, noting that 90% of the patients studied were at least 50 years of age and that 98% were fair skinned.

"Taken together, 89% of all Merkel cell carcinomas had three or more of these clinical AEIOU features," he said.

Optimal therapy for MCC is unique among skin cancers, he said, in that sentinel lymph node biopsy (SLNB) is usually indicated and the disease is "exquisitely sensitive" to radiation.

"If I had one modality to treat MCC, it would be radiation," he said.

SLNB is important for prognosis, he added, because it "results in more accurate staging and has therapeutic implications. If it's microscopically positive [the cancer] will very likely develop in that node bed within a few months if you don't do anything."

In Dr. Nghiem's opinion, the best local therapy for MCC is pathologically clear margins when the primary tumor is less than 1 cm, there is no lymphovascular invasion, there is no profound immune suppression, and the SLNB is negative.

"If all of those things are kosher, you are pretty much okay with a negative margin incision," he said. "Otherwise, adjuvant radiation is very helpful."

He described the current staging system for MCC as "a mess." Five staging systems are currently being used, he said, yet all of them are based on studies of fewer than 300 patients and none has been validated.

MCC staging by the American Joint Committee on Cancer is currently performed using the same staging system as for 82 other nonmelanoma skin cancers, including basal cell carcinoma, squamous cell carcinoma, and adnexal neoplasms.

The key histologic feature of MCC is a perinuclear dot pattern of cytokeratin-20, "which is the rule, not the exception," he said.

Dr. Nghiem finds MCC treatment guidelines from the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology to be especially useful. The guidelines are updated annually and are available at www.nccn.org

MCC typically is coded as ICD-9 code 173 (other malignant neoplasm of skin). "Unfortunately, this means that MCC costs can't be tracked at all and, more importantly, patients are denied care," he said. Things should improve on that front shortly, however. Dr. Nghiem said that the CDC is expected to release eight new diagnostic codes specific for MCC this month.

Little is known about MCC biology, but a study from 2008 found that a new polyomavirus is present in the vast majority of cases (Science 2008;319:1096-100). "This is only the sixth example of a virus clearly linked to human cancer," Dr. Nghiem said.

He disclosed that he has received funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the American Cancer Society.

The majority of Merkel cell carcinoma lesions appear on sun-exposed skin, but one in six has been found to appear on sun-protected areas.

Merkel cell carcinoma has a significantly higher mortality rate, compared with melanoma, and reported incidence has increased threefold since 1986.

Source Photos courtesy Dr. Paul Nghiem

PORTLAND, ORE. — Skin lesions are a hallmark of Merkel cell carcinoma, yet dermatologists often find themselves out of the loop in diagnosing patients with the disease, said Dr. Paul Nghiem.

"These [lesions] are typically biopsied as a cyst and the patient usually has to argue for one, two, or three doctor's visits to have the lesion biopsied," Dr. Nghiem said at the annual meeting of the Pacific Dermatologic Association. "They're usually biopsied by a reluctant primary care physician who thinks they're taking off a cyst. Then they may be referred to medical oncology or to surgical oncology, but rarely to dermatology."

About 1,500 new cases of Merkel cell carcinoma (MCC) are diagnosed in the United States each year (J. Invest. Dermatol. 2007;127:2100-3), which is about the same incidence as cutaneous T-cell lymphoma or dermatofibrosarcoma protuberans, said Dr. Nghiem, an expert on the disease who is associate professor of dermatology, medicine, and pathology at the University of Washington, Seattle.

MCC is significantly more lethal than melanoma (40% vs. 15%, respectively), and its reported incidence has increased threefold since 1986 (J. Surg. Oncol. 2005;89:1-4).

"A big reason for that is that it's not missed as much," Dr. Nghiem said. "There are better tools for pathologists to use to make the diagnosis."

The three main risk factors for MCC are prolonged sun exposure, immune suppression, and age over 50 years. "Ninety-four percent of all MCC cases are in people aged 50 or older," he said. "There is a very strong synergy with age" (J. Am. Acad. Dermatol. 2008;58:375-81).

Dr. Nghiem said that HIV-positive patients had about a 13-fold increase of MCC in one study (Lancet 2002;359:497-8), while another study showed that solid organ transplant recipients have about a 10-fold increase (Transplantation 1999;68:1717-21).

He and his associates devised the acronym AEIOU to describe the clinical features of Merkel cell carcinoma based on an analysis of 195 patients given the diagnosis between 1980 and 2007 (J. Am. Acad. Dermatol. 2008; 58:375-81). The acronym stands for Asymptomatic, Expanding rapidly, Immune compromised, Older than 50, and UV-exposed, fair skin.

"Under no circumstances do I think that this is a highly specific test," said Dr. Nghiem, whose clinic is based at the Fred Hutchinson Cancer Research Center in Seattle. "It's not going to be up there with the ABCDs of melanoma, but if you see these characteristics together, you may want to think about doing a biopsy."

More than half of the lesions in the 195 patients evaluated (56%) were presumed to be benign at biopsy, and 32% presented on the head and neck, followed by the lower limb (30%), upper limb (20%), trunk (10%), and buttock (8%).

The majority of lesions (81%) presented on sun-exposed skin, but one in six was in a sun-protected site.

Nearly all of the lesions (88%) were asymptomatic ("neither tender nor itchy," he said), 63% doubled in size in the past 3 months, and 8% of the patients were profoundly immune suppressed. "That is a 16-fold increase over the normal population, but still a minority of all Merkel cell cases," he said, noting that 90% of the patients studied were at least 50 years of age and that 98% were fair skinned.

"Taken together, 89% of all Merkel cell carcinomas had three or more of these clinical AEIOU features," he said.

Optimal therapy for MCC is unique among skin cancers, he said, in that sentinel lymph node biopsy (SLNB) is usually indicated and the disease is "exquisitely sensitive" to radiation.

"If I had one modality to treat MCC, it would be radiation," he said.

SLNB is important for prognosis, he added, because it "results in more accurate staging and has therapeutic implications. If it's microscopically positive [the cancer] will very likely develop in that node bed within a few months if you don't do anything."

In Dr. Nghiem's opinion, the best local therapy for MCC is pathologically clear margins when the primary tumor is less than 1 cm, there is no lymphovascular invasion, there is no profound immune suppression, and the SLNB is negative.

"If all of those things are kosher, you are pretty much okay with a negative margin incision," he said. "Otherwise, adjuvant radiation is very helpful."

He described the current staging system for MCC as "a mess." Five staging systems are currently being used, he said, yet all of them are based on studies of fewer than 300 patients and none has been validated.

MCC staging by the American Joint Committee on Cancer is currently performed using the same staging system as for 82 other nonmelanoma skin cancers, including basal cell carcinoma, squamous cell carcinoma, and adnexal neoplasms.

The key histologic feature of MCC is a perinuclear dot pattern of cytokeratin-20, "which is the rule, not the exception," he said.

Dr. Nghiem finds MCC treatment guidelines from the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology to be especially useful. The guidelines are updated annually and are available at www.nccn.org

MCC typically is coded as ICD-9 code 173 (other malignant neoplasm of skin). "Unfortunately, this means that MCC costs can't be tracked at all and, more importantly, patients are denied care," he said. Things should improve on that front shortly, however. Dr. Nghiem said that the CDC is expected to release eight new diagnostic codes specific for MCC this month.

Little is known about MCC biology, but a study from 2008 found that a new polyomavirus is present in the vast majority of cases (Science 2008;319:1096-100). "This is only the sixth example of a virus clearly linked to human cancer," Dr. Nghiem said.

He disclosed that he has received funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the American Cancer Society.

The majority of Merkel cell carcinoma lesions appear on sun-exposed skin, but one in six has been found to appear on sun-protected areas.

Merkel cell carcinoma has a significantly higher mortality rate, compared with melanoma, and reported incidence has increased threefold since 1986.

Source Photos courtesy Dr. Paul Nghiem

PORTLAND, ORE. — Skin lesions are a hallmark of Merkel cell carcinoma, yet dermatologists often find themselves out of the loop in diagnosing patients with the disease, said Dr. Paul Nghiem.

"These [lesions] are typically biopsied as a cyst and the patient usually has to argue for one, two, or three doctor's visits to have the lesion biopsied," Dr. Nghiem said at the annual meeting of the Pacific Dermatologic Association. "They're usually biopsied by a reluctant primary care physician who thinks they're taking off a cyst. Then they may be referred to medical oncology or to surgical oncology, but rarely to dermatology."

About 1,500 new cases of Merkel cell carcinoma (MCC) are diagnosed in the United States each year (J. Invest. Dermatol. 2007;127:2100-3), which is about the same incidence as cutaneous T-cell lymphoma or dermatofibrosarcoma protuberans, said Dr. Nghiem, an expert on the disease who is associate professor of dermatology, medicine, and pathology at the University of Washington, Seattle.

MCC is significantly more lethal than melanoma (40% vs. 15%, respectively), and its reported incidence has increased threefold since 1986 (J. Surg. Oncol. 2005;89:1-4).

"A big reason for that is that it's not missed as much," Dr. Nghiem said. "There are better tools for pathologists to use to make the diagnosis."

The three main risk factors for MCC are prolonged sun exposure, immune suppression, and age over 50 years. "Ninety-four percent of all MCC cases are in people aged 50 or older," he said. "There is a very strong synergy with age" (J. Am. Acad. Dermatol. 2008;58:375-81).

Dr. Nghiem said that HIV-positive patients had about a 13-fold increase of MCC in one study (Lancet 2002;359:497-8), while another study showed that solid organ transplant recipients have about a 10-fold increase (Transplantation 1999;68:1717-21).

He and his associates devised the acronym AEIOU to describe the clinical features of Merkel cell carcinoma based on an analysis of 195 patients given the diagnosis between 1980 and 2007 (J. Am. Acad. Dermatol. 2008; 58:375-81). The acronym stands for Asymptomatic, Expanding rapidly, Immune compromised, Older than 50, and UV-exposed, fair skin.

"Under no circumstances do I think that this is a highly specific test," said Dr. Nghiem, whose clinic is based at the Fred Hutchinson Cancer Research Center in Seattle. "It's not going to be up there with the ABCDs of melanoma, but if you see these characteristics together, you may want to think about doing a biopsy."

More than half of the lesions in the 195 patients evaluated (56%) were presumed to be benign at biopsy, and 32% presented on the head and neck, followed by the lower limb (30%), upper limb (20%), trunk (10%), and buttock (8%).

The majority of lesions (81%) presented on sun-exposed skin, but one in six was in a sun-protected site.

Nearly all of the lesions (88%) were asymptomatic ("neither tender nor itchy," he said), 63% doubled in size in the past 3 months, and 8% of the patients were profoundly immune suppressed. "That is a 16-fold increase over the normal population, but still a minority of all Merkel cell cases," he said, noting that 90% of the patients studied were at least 50 years of age and that 98% were fair skinned.

"Taken together, 89% of all Merkel cell carcinomas had three or more of these clinical AEIOU features," he said.

Optimal therapy for MCC is unique among skin cancers, he said, in that sentinel lymph node biopsy (SLNB) is usually indicated and the disease is "exquisitely sensitive" to radiation.

"If I had one modality to treat MCC, it would be radiation," he said.

SLNB is important for prognosis, he added, because it "results in more accurate staging and has therapeutic implications. If it's microscopically positive [the cancer] will very likely develop in that node bed within a few months if you don't do anything."

In Dr. Nghiem's opinion, the best local therapy for MCC is pathologically clear margins when the primary tumor is less than 1 cm, there is no lymphovascular invasion, there is no profound immune suppression, and the SLNB is negative.

"If all of those things are kosher, you are pretty much okay with a negative margin incision," he said. "Otherwise, adjuvant radiation is very helpful."

He described the current staging system for MCC as "a mess." Five staging systems are currently being used, he said, yet all of them are based on studies of fewer than 300 patients and none has been validated.

MCC staging by the American Joint Committee on Cancer is currently performed using the same staging system as for 82 other nonmelanoma skin cancers, including basal cell carcinoma, squamous cell carcinoma, and adnexal neoplasms.

The key histologic feature of MCC is a perinuclear dot pattern of cytokeratin-20, "which is the rule, not the exception," he said.

Dr. Nghiem finds MCC treatment guidelines from the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology to be especially useful. The guidelines are updated annually and are available at www.nccn.org

MCC typically is coded as ICD-9 code 173 (other malignant neoplasm of skin). "Unfortunately, this means that MCC costs can't be tracked at all and, more importantly, patients are denied care," he said. Things should improve on that front shortly, however. Dr. Nghiem said that the CDC is expected to release eight new diagnostic codes specific for MCC this month.

Little is known about MCC biology, but a study from 2008 found that a new polyomavirus is present in the vast majority of cases (Science 2008;319:1096-100). "This is only the sixth example of a virus clearly linked to human cancer," Dr. Nghiem said.

He disclosed that he has received funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the American Cancer Society.

The majority of Merkel cell carcinoma lesions appear on sun-exposed skin, but one in six has been found to appear on sun-protected areas.

Merkel cell carcinoma has a significantly higher mortality rate, compared with melanoma, and reported incidence has increased threefold since 1986.

Source Photos courtesy Dr. Paul Nghiem