Melanoma

MAUI, HAWAII — Look for tumor mitotic rate to supplant Clark level in the forthcoming 7th edition of the American Joint Committee on Cancer melanoma staging system.

“Clark level will now only be considered for staging in the rare instances when mitotic rate is not known; otherwise it will no longer be part of the staging system,” Dr. Jeffrey E. Gershenwald said at the annual Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation.

This represents a break with the past. Within melanoma staging, Clark level enjoyed near-equal billing with tumor thickness before being downgraded in clinical relevance in the still-current 6th edition of the AJCC staging system, issued in 2002.

The 6th edition relegated Clark level to a limited role, with Clark level IV and V resulting in upstaging of thin melanomas from T1 to T1b, explained Dr. Gershenwald, vice chair of the AJCC task force charged with developing the new edition of the staging system.

The 7th edition of the AJCC melanoma staging system will be published this spring and will take effect early next year. The same changes will be made in the European staging system in coordinated fashion.

Mitotic rate will be introduced into the staging system on the basis of recent evidence suggesting that it is an independent prognostic factor. The presence of at least one mitosis per square centimeter will be sufficient to upgrade a thin melanoma from T1 to T1b.

As the AJCC staging system is rolled out, reports will be issued detailing how pathologists should determine mitotic rate, according to Dr. Gershenwald, professor of surgery at the University of Texas M.D. Anderson Cancer Center, Houston.

Clark level, he added, has caused a great deal of confusion among patients, who often confuse Clark level IV with stage IV melanoma.

“I can't tell you how many patients have come into the clinic thinking they have a stage IV melanoma and are reading their death sentence on the Internet when in fact they might very well have had a thin melanoma that happens to be Clark level IV,” he commented.

“In dialoging with your patients, please make sure they understand the difference,” Dr. Gershenwald urged.

The 7th edition of the staging system will make no major changes in the core TNM (tumor, node, metastasis) and stage grouping criteria for stages I-III melanoma. A thin melanoma will remain one that's up to 1.0 mm in thickness, and a thick one will still have to be greater than 4.0 mm. This was an evidence-based decision in response to analysis of an international database of more than 50,000 melanoma patients which validated the models utilized in the 6th edition.

There will be a few minor changes in the 6th edition having clinical relevance, however. For one, there will no longer be a lower limit as to what constitutes node-positive disease.

Also, immunohistochemical detection of nodal metastases—already in wide use in clinical practice—will for the first time become acceptable for staging purposes in the upcoming edition, Dr. Gershenwald said.

In the 7th edition, the essential elements of a pathology report for primary melanoma will be Breslow thickness, the presence or absence of ulceration, mitotic rate, and margin status.

SDEF and this newspaper are owned by Elsevier.

The 7th edition will make no major changes in the core TNM and stage grouping criteria for stages I-III melanoma. DR. GERSHENWALD

Staging, Lymph Node Assessment Are Key to Surgical Melanoma Management

The surgical management of primary melanoma varies by patient and depends in large part on key elements of the pathology report and the assessment of lymph node involvement, according to Dr. Gershenwald.

In terms of staging the disease, Breslow thickness, ulceration, mitotic rate, Clark level, and margin assessment should be considered prior to wide local excision of the tumor, he noted.

And because nodal involvement is the best predictor of recurrence and survival in melanoma, determining which patients have lymph node involvement and which patients do not is critical to the optimal management of the disease.

Lymphatic mapping together with sentinel lymph node biopsy is a relatively noninvasive way to accurately stage the regional nodal basin and enables a selective approach to regional node dissection, whereby lymphadectomy is reserved only for patients found to have pathologically documented disease, Dr. Gershenwald explained.

This combined diagnostic approach—in which a radioactive tracer is injected around the primary tumor site and a blue dye is used to identify sentinel lymph nodes to be removed for analysis—identifies regional lymph node disease that might not be seen with complete lymph node dissection and identifies patients in whom adjuvant therapy is warranted, he said.

Studies have suggested that early detection by sentinel node biopsy of sentinel lymph node metastasis is associated with a survival benefit when compared with a watch-and-wait approach in patients who develop clinical lymph node recurrence, Dr. Gershenwald noted.

With respect to the use of fluorodeoxyglucose positron-emission tomography (FDG-PET), which has been shown in several reports to be a more sensitive indicator of metastatic melanoma than conventional imaging, limitations in the study designs may overestimate the utility of this imaging modality for this indication, he said.

The literature supports the use of adjunctive PET imaging in properly selected patients with metastatic or recurrent melanoma, but it does not provide evidence suggesting that FDG-PET should be obtained in all melanoma patients, he reported.

Specifically, FDG-PET rarely identifies the presence of occult distant metastases in early stage melanoma patients who have been staged using sentinel node biopsy, whch means the likelihood is low that these patients will be upstaged based on the FDG-PET results.

MAUI, HAWAII — Look for tumor mitotic rate to supplant Clark level in the forthcoming 7th edition of the American Joint Committee on Cancer melanoma staging system.

“Clark level will now only be considered for staging in the rare instances when mitotic rate is not known; otherwise it will no longer be part of the staging system,” Dr. Jeffrey E. Gershenwald said at the annual Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation.

This represents a break with the past. Within melanoma staging, Clark level enjoyed near-equal billing with tumor thickness before being downgraded in clinical relevance in the still-current 6th edition of the AJCC staging system, issued in 2002.

The 6th edition relegated Clark level to a limited role, with Clark level IV and V resulting in upstaging of thin melanomas from T1 to T1b, explained Dr. Gershenwald, vice chair of the AJCC task force charged with developing the new edition of the staging system.

The 7th edition of the AJCC melanoma staging system will be published this spring and will take effect early next year. The same changes will be made in the European staging system in coordinated fashion.

Mitotic rate will be introduced into the staging system on the basis of recent evidence suggesting that it is an independent prognostic factor. The presence of at least one mitosis per square centimeter will be sufficient to upgrade a thin melanoma from T1 to T1b.

As the AJCC staging system is rolled out, reports will be issued detailing how pathologists should determine mitotic rate, according to Dr. Gershenwald, professor of surgery at the University of Texas M.D. Anderson Cancer Center, Houston.

Clark level, he added, has caused a great deal of confusion among patients, who often confuse Clark level IV with stage IV melanoma.

“I can't tell you how many patients have come into the clinic thinking they have a stage IV melanoma and are reading their death sentence on the Internet when in fact they might very well have had a thin melanoma that happens to be Clark level IV,” he commented.

“In dialoging with your patients, please make sure they understand the difference,” Dr. Gershenwald urged.

The 7th edition of the staging system will make no major changes in the core TNM (tumor, node, metastasis) and stage grouping criteria for stages I-III melanoma. A thin melanoma will remain one that's up to 1.0 mm in thickness, and a thick one will still have to be greater than 4.0 mm. This was an evidence-based decision in response to analysis of an international database of more than 50,000 melanoma patients which validated the models utilized in the 6th edition.

There will be a few minor changes in the 6th edition having clinical relevance, however. For one, there will no longer be a lower limit as to what constitutes node-positive disease.

Also, immunohistochemical detection of nodal metastases—already in wide use in clinical practice—will for the first time become acceptable for staging purposes in the upcoming edition, Dr. Gershenwald said.

In the 7th edition, the essential elements of a pathology report for primary melanoma will be Breslow thickness, the presence or absence of ulceration, mitotic rate, and margin status.

SDEF and this newspaper are owned by Elsevier.

The 7th edition will make no major changes in the core TNM and stage grouping criteria for stages I-III melanoma. DR. GERSHENWALD

Staging, Lymph Node Assessment Are Key to Surgical Melanoma Management

The surgical management of primary melanoma varies by patient and depends in large part on key elements of the pathology report and the assessment of lymph node involvement, according to Dr. Gershenwald.

In terms of staging the disease, Breslow thickness, ulceration, mitotic rate, Clark level, and margin assessment should be considered prior to wide local excision of the tumor, he noted.

And because nodal involvement is the best predictor of recurrence and survival in melanoma, determining which patients have lymph node involvement and which patients do not is critical to the optimal management of the disease.

Lymphatic mapping together with sentinel lymph node biopsy is a relatively noninvasive way to accurately stage the regional nodal basin and enables a selective approach to regional node dissection, whereby lymphadectomy is reserved only for patients found to have pathologically documented disease, Dr. Gershenwald explained.

This combined diagnostic approach—in which a radioactive tracer is injected around the primary tumor site and a blue dye is used to identify sentinel lymph nodes to be removed for analysis—identifies regional lymph node disease that might not be seen with complete lymph node dissection and identifies patients in whom adjuvant therapy is warranted, he said.

Studies have suggested that early detection by sentinel node biopsy of sentinel lymph node metastasis is associated with a survival benefit when compared with a watch-and-wait approach in patients who develop clinical lymph node recurrence, Dr. Gershenwald noted.

With respect to the use of fluorodeoxyglucose positron-emission tomography (FDG-PET), which has been shown in several reports to be a more sensitive indicator of metastatic melanoma than conventional imaging, limitations in the study designs may overestimate the utility of this imaging modality for this indication, he said.

The literature supports the use of adjunctive PET imaging in properly selected patients with metastatic or recurrent melanoma, but it does not provide evidence suggesting that FDG-PET should be obtained in all melanoma patients, he reported.

Specifically, FDG-PET rarely identifies the presence of occult distant metastases in early stage melanoma patients who have been staged using sentinel node biopsy, whch means the likelihood is low that these patients will be upstaged based on the FDG-PET results.

MAUI, HAWAII — Look for tumor mitotic rate to supplant Clark level in the forthcoming 7th edition of the American Joint Committee on Cancer melanoma staging system.

“Clark level will now only be considered for staging in the rare instances when mitotic rate is not known; otherwise it will no longer be part of the staging system,” Dr. Jeffrey E. Gershenwald said at the annual Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation.

This represents a break with the past. Within melanoma staging, Clark level enjoyed near-equal billing with tumor thickness before being downgraded in clinical relevance in the still-current 6th edition of the AJCC staging system, issued in 2002.

The 6th edition relegated Clark level to a limited role, with Clark level IV and V resulting in upstaging of thin melanomas from T1 to T1b, explained Dr. Gershenwald, vice chair of the AJCC task force charged with developing the new edition of the staging system.

The 7th edition of the AJCC melanoma staging system will be published this spring and will take effect early next year. The same changes will be made in the European staging system in coordinated fashion.

Mitotic rate will be introduced into the staging system on the basis of recent evidence suggesting that it is an independent prognostic factor. The presence of at least one mitosis per square centimeter will be sufficient to upgrade a thin melanoma from T1 to T1b.

As the AJCC staging system is rolled out, reports will be issued detailing how pathologists should determine mitotic rate, according to Dr. Gershenwald, professor of surgery at the University of Texas M.D. Anderson Cancer Center, Houston.

Clark level, he added, has caused a great deal of confusion among patients, who often confuse Clark level IV with stage IV melanoma.

“I can't tell you how many patients have come into the clinic thinking they have a stage IV melanoma and are reading their death sentence on the Internet when in fact they might very well have had a thin melanoma that happens to be Clark level IV,” he commented.

“In dialoging with your patients, please make sure they understand the difference,” Dr. Gershenwald urged.

The 7th edition of the staging system will make no major changes in the core TNM (tumor, node, metastasis) and stage grouping criteria for stages I-III melanoma. A thin melanoma will remain one that's up to 1.0 mm in thickness, and a thick one will still have to be greater than 4.0 mm. This was an evidence-based decision in response to analysis of an international database of more than 50,000 melanoma patients which validated the models utilized in the 6th edition.

There will be a few minor changes in the 6th edition having clinical relevance, however. For one, there will no longer be a lower limit as to what constitutes node-positive disease.

Also, immunohistochemical detection of nodal metastases—already in wide use in clinical practice—will for the first time become acceptable for staging purposes in the upcoming edition, Dr. Gershenwald said.

In the 7th edition, the essential elements of a pathology report for primary melanoma will be Breslow thickness, the presence or absence of ulceration, mitotic rate, and margin status.

SDEF and this newspaper are owned by Elsevier.

The 7th edition will make no major changes in the core TNM and stage grouping criteria for stages I-III melanoma. DR. GERSHENWALD

Staging, Lymph Node Assessment Are Key to Surgical Melanoma Management

The surgical management of primary melanoma varies by patient and depends in large part on key elements of the pathology report and the assessment of lymph node involvement, according to Dr. Gershenwald.

In terms of staging the disease, Breslow thickness, ulceration, mitotic rate, Clark level, and margin assessment should be considered prior to wide local excision of the tumor, he noted.

And because nodal involvement is the best predictor of recurrence and survival in melanoma, determining which patients have lymph node involvement and which patients do not is critical to the optimal management of the disease.

Lymphatic mapping together with sentinel lymph node biopsy is a relatively noninvasive way to accurately stage the regional nodal basin and enables a selective approach to regional node dissection, whereby lymphadectomy is reserved only for patients found to have pathologically documented disease, Dr. Gershenwald explained.

This combined diagnostic approach—in which a radioactive tracer is injected around the primary tumor site and a blue dye is used to identify sentinel lymph nodes to be removed for analysis—identifies regional lymph node disease that might not be seen with complete lymph node dissection and identifies patients in whom adjuvant therapy is warranted, he said.

Studies have suggested that early detection by sentinel node biopsy of sentinel lymph node metastasis is associated with a survival benefit when compared with a watch-and-wait approach in patients who develop clinical lymph node recurrence, Dr. Gershenwald noted.

With respect to the use of fluorodeoxyglucose positron-emission tomography (FDG-PET), which has been shown in several reports to be a more sensitive indicator of metastatic melanoma than conventional imaging, limitations in the study designs may overestimate the utility of this imaging modality for this indication, he said.

The literature supports the use of adjunctive PET imaging in properly selected patients with metastatic or recurrent melanoma, but it does not provide evidence suggesting that FDG-PET should be obtained in all melanoma patients, he reported.

Specifically, FDG-PET rarely identifies the presence of occult distant metastases in early stage melanoma patients who have been staged using sentinel node biopsy, whch means the likelihood is low that these patients will be upstaged based on the FDG-PET results.

SAN FRANCISCO — When a dermatopathologist butts heads with a pathologist over a diagnosis, it helps to keep the patient in mind.

"What do you do when your opinion differs radically from that of the contributing pathologist?" asked Dr. Dirk M. Elston, director of dermatology at Geisinger Medical Center, Danville, Pa. "You're getting cases … from all over the country. What you get to look at is sometimes not what the contributor thought. Sometimes it's a sticky situation."

Persistence in the face of diagnostic conflicts—especially when a malignancy is at issue—may be needed to achieve the appropriate treatment. "As long as we keep the patient in mind, we're doing the right thing," said Dr. Elston, who moderated a session at the annual meeting of the American Society of Dermatopathology in which speakers gave examples of cases in which their diagnostic opinions differed from others.

Dr. Ronald P. Rapini described an elderly male patient who had a spindle cell neoplasm on his face in the background of solar elastosis. The biopsy showed relatively bland spindle cells going through the fibrotic sun-damaged dermis. Some areas showed cells that were a little bit atypical, but not strikingly so.

When he looked around the sample more, however, he saw progressively more atypical cells and eventually diagnosed an atypical fibroxanthoma, using the appropriate diagnostic stains, recalled Dr. Rapini, professor and chair of dermatology at the University of Texas M.D. Anderson Cancer Center, Houston.

The patient decided to see a head and neck surgeon at another institution, which requested the biopsy slides for review by their own pathologist. "I'll call him Dr. B, because he diagnosed it as benign," Dr. Rapini said. Dr. B told the head and neck surgeon that the patient had a benign lesion that didn't need excision.

"What would you do?" Dr. Rapini asked. He called a dermatopathologist at the other institution—"I'll call him Dr. C"—and asked him to talk with Dr. B, the pathologist, to request that he at least put an addendum on his report to acknowledge that there was an alternative opinion saying this might be an atypical fibroxanthoma and that it was not a clear-cut case. "So maybe the head and neck surgeon might actually remove the lesion," Dr. Rapini said.

Dr. C reviewed the case and agreed that the lesion looked like an atypical fibroxanthoma. He did speak with Dr. B, but Dr. B refused to modify his pathology report in any way, insisting that this was a benign lesion. Although both Dr. B and Dr. C worked at the same institution, Dr. C felt it would be inappropriate for Dr. C to make an addendum himself on a colleague's case.

"Now what would you do?" Dr. Rapini asked. He asked Dr. C to talk to the head of his institution's pathology department to see what the chair would say. "The actions of the head of the department are not known to me," Dr. Rapini said. The pathology report basically stayed the same.

"Now what would you do?" he repeated. Dr. Rapini called the head and neck surgeon directly to inform him of the alternative opinion, and that Dr. Rapini had diagnosed the lesion as an atypical fibroxanthoma that should be removed.

The surgeon reexcised the area and sent the surgical specimen to the institution's dermatopathologist, who declared it an atypical fibroxanthoma with clear surgical margins. "So it had a happy ending," Dr. Rapini said.

Dr. Elston praised him for sticking with the case: "You were willing to persist, and kept in mind that there was a patient at the other end who had a malignancy that was not being treated appropriately."

Persistence in the face of diagnostic conflicts may be needed to achieve the appropriate treatment. DR. ELSTON

SAN FRANCISCO — When a dermatopathologist butts heads with a pathologist over a diagnosis, it helps to keep the patient in mind.

"What do you do when your opinion differs radically from that of the contributing pathologist?" asked Dr. Dirk M. Elston, director of dermatology at Geisinger Medical Center, Danville, Pa. "You're getting cases … from all over the country. What you get to look at is sometimes not what the contributor thought. Sometimes it's a sticky situation."

Persistence in the face of diagnostic conflicts—especially when a malignancy is at issue—may be needed to achieve the appropriate treatment. "As long as we keep the patient in mind, we're doing the right thing," said Dr. Elston, who moderated a session at the annual meeting of the American Society of Dermatopathology in which speakers gave examples of cases in which their diagnostic opinions differed from others.

Dr. Ronald P. Rapini described an elderly male patient who had a spindle cell neoplasm on his face in the background of solar elastosis. The biopsy showed relatively bland spindle cells going through the fibrotic sun-damaged dermis. Some areas showed cells that were a little bit atypical, but not strikingly so.

When he looked around the sample more, however, he saw progressively more atypical cells and eventually diagnosed an atypical fibroxanthoma, using the appropriate diagnostic stains, recalled Dr. Rapini, professor and chair of dermatology at the University of Texas M.D. Anderson Cancer Center, Houston.

The patient decided to see a head and neck surgeon at another institution, which requested the biopsy slides for review by their own pathologist. "I'll call him Dr. B, because he diagnosed it as benign," Dr. Rapini said. Dr. B told the head and neck surgeon that the patient had a benign lesion that didn't need excision.

"What would you do?" Dr. Rapini asked. He called a dermatopathologist at the other institution—"I'll call him Dr. C"—and asked him to talk with Dr. B, the pathologist, to request that he at least put an addendum on his report to acknowledge that there was an alternative opinion saying this might be an atypical fibroxanthoma and that it was not a clear-cut case. "So maybe the head and neck surgeon might actually remove the lesion," Dr. Rapini said.

Dr. C reviewed the case and agreed that the lesion looked like an atypical fibroxanthoma. He did speak with Dr. B, but Dr. B refused to modify his pathology report in any way, insisting that this was a benign lesion. Although both Dr. B and Dr. C worked at the same institution, Dr. C felt it would be inappropriate for Dr. C to make an addendum himself on a colleague's case.

"Now what would you do?" Dr. Rapini asked. He asked Dr. C to talk to the head of his institution's pathology department to see what the chair would say. "The actions of the head of the department are not known to me," Dr. Rapini said. The pathology report basically stayed the same.

"Now what would you do?" he repeated. Dr. Rapini called the head and neck surgeon directly to inform him of the alternative opinion, and that Dr. Rapini had diagnosed the lesion as an atypical fibroxanthoma that should be removed.

The surgeon reexcised the area and sent the surgical specimen to the institution's dermatopathologist, who declared it an atypical fibroxanthoma with clear surgical margins. "So it had a happy ending," Dr. Rapini said.

Dr. Elston praised him for sticking with the case: "You were willing to persist, and kept in mind that there was a patient at the other end who had a malignancy that was not being treated appropriately."

Persistence in the face of diagnostic conflicts may be needed to achieve the appropriate treatment. DR. ELSTON

SAN FRANCISCO — When a dermatopathologist butts heads with a pathologist over a diagnosis, it helps to keep the patient in mind.

"What do you do when your opinion differs radically from that of the contributing pathologist?" asked Dr. Dirk M. Elston, director of dermatology at Geisinger Medical Center, Danville, Pa. "You're getting cases … from all over the country. What you get to look at is sometimes not what the contributor thought. Sometimes it's a sticky situation."

Persistence in the face of diagnostic conflicts—especially when a malignancy is at issue—may be needed to achieve the appropriate treatment. "As long as we keep the patient in mind, we're doing the right thing," said Dr. Elston, who moderated a session at the annual meeting of the American Society of Dermatopathology in which speakers gave examples of cases in which their diagnostic opinions differed from others.

Dr. Ronald P. Rapini described an elderly male patient who had a spindle cell neoplasm on his face in the background of solar elastosis. The biopsy showed relatively bland spindle cells going through the fibrotic sun-damaged dermis. Some areas showed cells that were a little bit atypical, but not strikingly so.

When he looked around the sample more, however, he saw progressively more atypical cells and eventually diagnosed an atypical fibroxanthoma, using the appropriate diagnostic stains, recalled Dr. Rapini, professor and chair of dermatology at the University of Texas M.D. Anderson Cancer Center, Houston.

The patient decided to see a head and neck surgeon at another institution, which requested the biopsy slides for review by their own pathologist. "I'll call him Dr. B, because he diagnosed it as benign," Dr. Rapini said. Dr. B told the head and neck surgeon that the patient had a benign lesion that didn't need excision.

"What would you do?" Dr. Rapini asked. He called a dermatopathologist at the other institution—"I'll call him Dr. C"—and asked him to talk with Dr. B, the pathologist, to request that he at least put an addendum on his report to acknowledge that there was an alternative opinion saying this might be an atypical fibroxanthoma and that it was not a clear-cut case. "So maybe the head and neck surgeon might actually remove the lesion," Dr. Rapini said.

Dr. C reviewed the case and agreed that the lesion looked like an atypical fibroxanthoma. He did speak with Dr. B, but Dr. B refused to modify his pathology report in any way, insisting that this was a benign lesion. Although both Dr. B and Dr. C worked at the same institution, Dr. C felt it would be inappropriate for Dr. C to make an addendum himself on a colleague's case.

"Now what would you do?" Dr. Rapini asked. He asked Dr. C to talk to the head of his institution's pathology department to see what the chair would say. "The actions of the head of the department are not known to me," Dr. Rapini said. The pathology report basically stayed the same.

"Now what would you do?" he repeated. Dr. Rapini called the head and neck surgeon directly to inform him of the alternative opinion, and that Dr. Rapini had diagnosed the lesion as an atypical fibroxanthoma that should be removed.

The surgeon reexcised the area and sent the surgical specimen to the institution's dermatopathologist, who declared it an atypical fibroxanthoma with clear surgical margins. "So it had a happy ending," Dr. Rapini said.

Dr. Elston praised him for sticking with the case: "You were willing to persist, and kept in mind that there was a patient at the other end who had a malignancy that was not being treated appropriately."

Persistence in the face of diagnostic conflicts may be needed to achieve the appropriate treatment. DR. ELSTON

SAN FRANCISCO — The diagnosis of blastic natural killer-cell lymphoma requires a dermatopathologist who knows the typical immunohistochemical patterns of the disease and is aware of exceptions to rules.

Also called CD4-positive, CD56-positive (CD4+/CD56+) hematodermic neoplasm, the disease is a rare, aggressive malignancy that frequently presents with skin lesions. Immunohistochemical staining typically produces immunopositivity for CD4, CD56, and CD123, but rare cases have been reported of patients who tested negative in one or more of these immunohistochemical studies.

At the annual meeting of the American Society of Dermatopathology, Dr. Rajwant Malhotra and Dr. Alison L. Uzieblo reported on two cases of CD4+/CD56+ hematodermic neoplasm presenting as skin nodules and plaques. One of the cases in their poster was CD123-negative.

"Loss of CD123 expression is a distinctly unusual event" in CD4+/CD56+ hematodermic neoplasm, wrote the authors, both from the anatomic pathology department at Beaumont Hospital, Royal Oak, Mich. Given the poor prognosis associated with this disease, "it is important to be aware of this potential phenomenon when evaluating cutaneous hematolymphoid malignancies."

One patient was a 77-year-old man who presented with skin lesions on his back and trunk. Flow cytometric analysis subsequently showed bone marrow involvement. The second patient, a 70-year-old man, had a 3-cm nodular plaque on his scalp. Further clinical evaluation found no evidence of bone marrow involvement.

Histological examination of biopsies from both patients revealed dense dermal infiltrates composed of sheets of medium-sized cells with angulated to round nuclear contours in the dermis. The lesional cells were positive for CD4, CD43, and CD56, but only one patient's biopsy demonstrated CD123 positivity. Both showed a high proliferation rate with Ki-67 staining noted in approximately 50% of cells in one patient and 70% of cells in the other.

SAN FRANCISCO — The diagnosis of blastic natural killer-cell lymphoma requires a dermatopathologist who knows the typical immunohistochemical patterns of the disease and is aware of exceptions to rules.

Also called CD4-positive, CD56-positive (CD4+/CD56+) hematodermic neoplasm, the disease is a rare, aggressive malignancy that frequently presents with skin lesions. Immunohistochemical staining typically produces immunopositivity for CD4, CD56, and CD123, but rare cases have been reported of patients who tested negative in one or more of these immunohistochemical studies.

At the annual meeting of the American Society of Dermatopathology, Dr. Rajwant Malhotra and Dr. Alison L. Uzieblo reported on two cases of CD4+/CD56+ hematodermic neoplasm presenting as skin nodules and plaques. One of the cases in their poster was CD123-negative.

"Loss of CD123 expression is a distinctly unusual event" in CD4+/CD56+ hematodermic neoplasm, wrote the authors, both from the anatomic pathology department at Beaumont Hospital, Royal Oak, Mich. Given the poor prognosis associated with this disease, "it is important to be aware of this potential phenomenon when evaluating cutaneous hematolymphoid malignancies."

One patient was a 77-year-old man who presented with skin lesions on his back and trunk. Flow cytometric analysis subsequently showed bone marrow involvement. The second patient, a 70-year-old man, had a 3-cm nodular plaque on his scalp. Further clinical evaluation found no evidence of bone marrow involvement.

Histological examination of biopsies from both patients revealed dense dermal infiltrates composed of sheets of medium-sized cells with angulated to round nuclear contours in the dermis. The lesional cells were positive for CD4, CD43, and CD56, but only one patient's biopsy demonstrated CD123 positivity. Both showed a high proliferation rate with Ki-67 staining noted in approximately 50% of cells in one patient and 70% of cells in the other.

SAN FRANCISCO — The diagnosis of blastic natural killer-cell lymphoma requires a dermatopathologist who knows the typical immunohistochemical patterns of the disease and is aware of exceptions to rules.

Also called CD4-positive, CD56-positive (CD4+/CD56+) hematodermic neoplasm, the disease is a rare, aggressive malignancy that frequently presents with skin lesions. Immunohistochemical staining typically produces immunopositivity for CD4, CD56, and CD123, but rare cases have been reported of patients who tested negative in one or more of these immunohistochemical studies.

At the annual meeting of the American Society of Dermatopathology, Dr. Rajwant Malhotra and Dr. Alison L. Uzieblo reported on two cases of CD4+/CD56+ hematodermic neoplasm presenting as skin nodules and plaques. One of the cases in their poster was CD123-negative.

"Loss of CD123 expression is a distinctly unusual event" in CD4+/CD56+ hematodermic neoplasm, wrote the authors, both from the anatomic pathology department at Beaumont Hospital, Royal Oak, Mich. Given the poor prognosis associated with this disease, "it is important to be aware of this potential phenomenon when evaluating cutaneous hematolymphoid malignancies."

One patient was a 77-year-old man who presented with skin lesions on his back and trunk. Flow cytometric analysis subsequently showed bone marrow involvement. The second patient, a 70-year-old man, had a 3-cm nodular plaque on his scalp. Further clinical evaluation found no evidence of bone marrow involvement.

Histological examination of biopsies from both patients revealed dense dermal infiltrates composed of sheets of medium-sized cells with angulated to round nuclear contours in the dermis. The lesional cells were positive for CD4, CD43, and CD56, but only one patient's biopsy demonstrated CD123 positivity. Both showed a high proliferation rate with Ki-67 staining noted in approximately 50% of cells in one patient and 70% of cells in the other.

ORLANDO — It is possible that the presence of micrometastases on sentinel lymph node biopsy may have little clinical prognostic value when predicting the survival of patients with malignant melanoma, according to a review of 415 patients.

The overall survival of those who had micrometastases less than 1 cm was similar to the overall survival achieved by patients with no metastases, Dr. Arun P. Venkat reported at the annual meeting of the American Society for Dermatologic Surgery.

In contrast, overall survival was significantly worse in patients who had macrometastases greater than 1 cm, said Dr. Venkat.

Micrometastases are most often detected with sentinel lymph node biopsy (SLNB), whereas macrometastases can be detected clinically or with positron emission tomography/computed tomography (PET/CT).

"Improved immunohistologic techniques are making it easier to find micrometastases in malignant melanoma, so the real question is whether micrometastases are an accurate predictor of recurrences and prognosis or are we unnecessarily upstaging patients by finding more micrometastases?" said Dr. Venkat, who is a dermatology resident at the University of Iowa Hospitals and Clinics in Iowa City.

The prognostic relevance of micrometastases versus macrometastases "has not been clearly differentiated," he noted.

The 415 patients had been followed for at least 3 months: 73 were deemed to have micrometastases, as evidenced by SLNB, and 81 had macrometastases as evidenced by PET/CT. Patients with macrometastases had a significantly lower probability of survival. Their hazard ratio for all causes of death was 3.73, compared with 2.03 in patients with micrometastastes.

The survival difference between macrometastases versus micrometastases and macrometastases versus no metastases was significant, but the difference between micrometastases and no metastases was not significant, he noted.

"The statistically significant difference in survival using the log-rank test had the following P values: P equal to .029 for macrometastases versus micrometastases, and P less than .0001 for macrometastases versus micrometastases," he said. Adding that "The difference in survival between micrometastases and no metastases was not statistically significant, with a P value of .148."

He offered some explanations as to why micro- and macrometastases would differ prognostically.

"Micrometastases may actually be false positives, as benign nevi can have nevus rests in lymph nodes. Additionally, they might also act as an antigen to activate the immune system to fight against the cutaneous malignant melanoma," he said.

"A few malignant cells in the sentinel lymph nodes may not mean that the prognosis is poor," he added. "The melanoma cells in the lymph nodes may activate the immune system and actually cause an immune response."

Dr. Venkat said he had no conflicts of interest to declare relevant to his presentation.

He noted that the study was funded by an American Society of Dermatologic Surgery Cutting Edge Research Grant.

'Micrometastases may actually be false positives, as benign nevi can have nevus rests in lymph nodes.' DR. VENKAT

ORLANDO — It is possible that the presence of micrometastases on sentinel lymph node biopsy may have little clinical prognostic value when predicting the survival of patients with malignant melanoma, according to a review of 415 patients.

The overall survival of those who had micrometastases less than 1 cm was similar to the overall survival achieved by patients with no metastases, Dr. Arun P. Venkat reported at the annual meeting of the American Society for Dermatologic Surgery.

In contrast, overall survival was significantly worse in patients who had macrometastases greater than 1 cm, said Dr. Venkat.

Micrometastases are most often detected with sentinel lymph node biopsy (SLNB), whereas macrometastases can be detected clinically or with positron emission tomography/computed tomography (PET/CT).

"Improved immunohistologic techniques are making it easier to find micrometastases in malignant melanoma, so the real question is whether micrometastases are an accurate predictor of recurrences and prognosis or are we unnecessarily upstaging patients by finding more micrometastases?" said Dr. Venkat, who is a dermatology resident at the University of Iowa Hospitals and Clinics in Iowa City.

The prognostic relevance of micrometastases versus macrometastases "has not been clearly differentiated," he noted.

The 415 patients had been followed for at least 3 months: 73 were deemed to have micrometastases, as evidenced by SLNB, and 81 had macrometastases as evidenced by PET/CT. Patients with macrometastases had a significantly lower probability of survival. Their hazard ratio for all causes of death was 3.73, compared with 2.03 in patients with micrometastastes.

The survival difference between macrometastases versus micrometastases and macrometastases versus no metastases was significant, but the difference between micrometastases and no metastases was not significant, he noted.

"The statistically significant difference in survival using the log-rank test had the following P values: P equal to .029 for macrometastases versus micrometastases, and P less than .0001 for macrometastases versus micrometastases," he said. Adding that "The difference in survival between micrometastases and no metastases was not statistically significant, with a P value of .148."

He offered some explanations as to why micro- and macrometastases would differ prognostically.

"Micrometastases may actually be false positives, as benign nevi can have nevus rests in lymph nodes. Additionally, they might also act as an antigen to activate the immune system to fight against the cutaneous malignant melanoma," he said.

"A few malignant cells in the sentinel lymph nodes may not mean that the prognosis is poor," he added. "The melanoma cells in the lymph nodes may activate the immune system and actually cause an immune response."

Dr. Venkat said he had no conflicts of interest to declare relevant to his presentation.

He noted that the study was funded by an American Society of Dermatologic Surgery Cutting Edge Research Grant.

'Micrometastases may actually be false positives, as benign nevi can have nevus rests in lymph nodes.' DR. VENKAT

ORLANDO — It is possible that the presence of micrometastases on sentinel lymph node biopsy may have little clinical prognostic value when predicting the survival of patients with malignant melanoma, according to a review of 415 patients.

The overall survival of those who had micrometastases less than 1 cm was similar to the overall survival achieved by patients with no metastases, Dr. Arun P. Venkat reported at the annual meeting of the American Society for Dermatologic Surgery.

In contrast, overall survival was significantly worse in patients who had macrometastases greater than 1 cm, said Dr. Venkat.

Micrometastases are most often detected with sentinel lymph node biopsy (SLNB), whereas macrometastases can be detected clinically or with positron emission tomography/computed tomography (PET/CT).

"Improved immunohistologic techniques are making it easier to find micrometastases in malignant melanoma, so the real question is whether micrometastases are an accurate predictor of recurrences and prognosis or are we unnecessarily upstaging patients by finding more micrometastases?" said Dr. Venkat, who is a dermatology resident at the University of Iowa Hospitals and Clinics in Iowa City.

The prognostic relevance of micrometastases versus macrometastases "has not been clearly differentiated," he noted.

The 415 patients had been followed for at least 3 months: 73 were deemed to have micrometastases, as evidenced by SLNB, and 81 had macrometastases as evidenced by PET/CT. Patients with macrometastases had a significantly lower probability of survival. Their hazard ratio for all causes of death was 3.73, compared with 2.03 in patients with micrometastastes.

The survival difference between macrometastases versus micrometastases and macrometastases versus no metastases was significant, but the difference between micrometastases and no metastases was not significant, he noted.

"The statistically significant difference in survival using the log-rank test had the following P values: P equal to .029 for macrometastases versus micrometastases, and P less than .0001 for macrometastases versus micrometastases," he said. Adding that "The difference in survival between micrometastases and no metastases was not statistically significant, with a P value of .148."

He offered some explanations as to why micro- and macrometastases would differ prognostically.

"Micrometastases may actually be false positives, as benign nevi can have nevus rests in lymph nodes. Additionally, they might also act as an antigen to activate the immune system to fight against the cutaneous malignant melanoma," he said.

"A few malignant cells in the sentinel lymph nodes may not mean that the prognosis is poor," he added. "The melanoma cells in the lymph nodes may activate the immune system and actually cause an immune response."

Dr. Venkat said he had no conflicts of interest to declare relevant to his presentation.

He noted that the study was funded by an American Society of Dermatologic Surgery Cutting Edge Research Grant.

'Micrometastases may actually be false positives, as benign nevi can have nevus rests in lymph nodes.' DR. VENKAT

ORLANDO — Patients who receive multiple solid organ transplants appear to be at significantly higher risk of developing cutaneous malignancy—specifically melanoma and nonmelanoma skin cancer—after their transplants, compared with patients who have had only one transplant.

A total of 6 (26%) of 23 patients who received two or more transplants reported having at least one posttransplant skin cancer, compared with 23 (8%) of 297 patients who had only one transplant. This difference between multiple and single organ transplant recipients was statistically significant, Dr. Murad Alam said at the annual meeting of the American Society for Dermatologic Surgery.

Using a database that was jointly developed by the departments of organ transplantation and dermatology at Northwestern University, Chicago, Dr. Alam and colleagues contacted 320 patients (mean age, 54 years) who received transplanted organs more than 4 years previously. Their transplants included kidney, liver, heart, lung, and pancreas.

The patients were interviewed for 30 minutes by telephone, and asked about their medical and surgical history, including whether they had diabetes. "We postulated that the patients with diabetes who may have had prolonged immunosuppression prior to their transplant might also have a greater incidence of skin cancers after their transplants," explained Dr. Alam of Northwestern.

The patients also provided dates and type of skin cancer, if any, that had developed since their transplants.

Diabetes was not a factor in developing a subsequent skin cancer. Of 91 patients with diabetes, 10 (11%) developed skin cancer, compared with 19 (8%) of 229 patients without diabetes, Dr. Alam said.

The finding that multiple organ transplant is associated with a higher rate of subsequent skin cancer than single organ transplant raises other questions that cannot be answered by a study cohort of this size, he added.

A study with a larger cohort might be able to answer these questions:

▸ Is there a causal link between multiple organ transplants and skin cancer?

▸ Are the risks different for different types of cancer?

▸ Do other comorbidities or medications have an impact on the likelihood of skin cancer in multiple organ transplant recipients?

▸ Which is more likely to increase the risk of skin cancer, concurrent transplants or sequential transplants?

▸ Are there specific types of transplants or specific pairs of transplants that produce greater risk for skin cancer?

"If we can find answers to these questions, we will then be able to tell which patients need to undergo the closest scrutiny for early management of their cancers," Dr. Alam concluded. He disclosed having no conflicts of interest.

The study also found that diabetes was not a factor in developing a subsequent skin cancer. DR. ALAM

ELSEVIER GLOBAL MEDICAL NEWS

ORLANDO — Patients who receive multiple solid organ transplants appear to be at significantly higher risk of developing cutaneous malignancy—specifically melanoma and nonmelanoma skin cancer—after their transplants, compared with patients who have had only one transplant.

A total of 6 (26%) of 23 patients who received two or more transplants reported having at least one posttransplant skin cancer, compared with 23 (8%) of 297 patients who had only one transplant. This difference between multiple and single organ transplant recipients was statistically significant, Dr. Murad Alam said at the annual meeting of the American Society for Dermatologic Surgery.

Using a database that was jointly developed by the departments of organ transplantation and dermatology at Northwestern University, Chicago, Dr. Alam and colleagues contacted 320 patients (mean age, 54 years) who received transplanted organs more than 4 years previously. Their transplants included kidney, liver, heart, lung, and pancreas.

The patients were interviewed for 30 minutes by telephone, and asked about their medical and surgical history, including whether they had diabetes. "We postulated that the patients with diabetes who may have had prolonged immunosuppression prior to their transplant might also have a greater incidence of skin cancers after their transplants," explained Dr. Alam of Northwestern.

The patients also provided dates and type of skin cancer, if any, that had developed since their transplants.

Diabetes was not a factor in developing a subsequent skin cancer. Of 91 patients with diabetes, 10 (11%) developed skin cancer, compared with 19 (8%) of 229 patients without diabetes, Dr. Alam said.

The finding that multiple organ transplant is associated with a higher rate of subsequent skin cancer than single organ transplant raises other questions that cannot be answered by a study cohort of this size, he added.

A study with a larger cohort might be able to answer these questions:

▸ Is there a causal link between multiple organ transplants and skin cancer?

▸ Are the risks different for different types of cancer?

▸ Do other comorbidities or medications have an impact on the likelihood of skin cancer in multiple organ transplant recipients?

▸ Which is more likely to increase the risk of skin cancer, concurrent transplants or sequential transplants?

▸ Are there specific types of transplants or specific pairs of transplants that produce greater risk for skin cancer?

"If we can find answers to these questions, we will then be able to tell which patients need to undergo the closest scrutiny for early management of their cancers," Dr. Alam concluded. He disclosed having no conflicts of interest.

The study also found that diabetes was not a factor in developing a subsequent skin cancer. DR. ALAM

ELSEVIER GLOBAL MEDICAL NEWS

ORLANDO — Patients who receive multiple solid organ transplants appear to be at significantly higher risk of developing cutaneous malignancy—specifically melanoma and nonmelanoma skin cancer—after their transplants, compared with patients who have had only one transplant.

A total of 6 (26%) of 23 patients who received two or more transplants reported having at least one posttransplant skin cancer, compared with 23 (8%) of 297 patients who had only one transplant. This difference between multiple and single organ transplant recipients was statistically significant, Dr. Murad Alam said at the annual meeting of the American Society for Dermatologic Surgery.

Using a database that was jointly developed by the departments of organ transplantation and dermatology at Northwestern University, Chicago, Dr. Alam and colleagues contacted 320 patients (mean age, 54 years) who received transplanted organs more than 4 years previously. Their transplants included kidney, liver, heart, lung, and pancreas.

The patients were interviewed for 30 minutes by telephone, and asked about their medical and surgical history, including whether they had diabetes. "We postulated that the patients with diabetes who may have had prolonged immunosuppression prior to their transplant might also have a greater incidence of skin cancers after their transplants," explained Dr. Alam of Northwestern.

The patients also provided dates and type of skin cancer, if any, that had developed since their transplants.

Diabetes was not a factor in developing a subsequent skin cancer. Of 91 patients with diabetes, 10 (11%) developed skin cancer, compared with 19 (8%) of 229 patients without diabetes, Dr. Alam said.

The finding that multiple organ transplant is associated with a higher rate of subsequent skin cancer than single organ transplant raises other questions that cannot be answered by a study cohort of this size, he added.

A study with a larger cohort might be able to answer these questions:

▸ Is there a causal link between multiple organ transplants and skin cancer?

▸ Are the risks different for different types of cancer?

▸ Do other comorbidities or medications have an impact on the likelihood of skin cancer in multiple organ transplant recipients?

▸ Which is more likely to increase the risk of skin cancer, concurrent transplants or sequential transplants?

▸ Are there specific types of transplants or specific pairs of transplants that produce greater risk for skin cancer?

"If we can find answers to these questions, we will then be able to tell which patients need to undergo the closest scrutiny for early management of their cancers," Dr. Alam concluded. He disclosed having no conflicts of interest.

The study also found that diabetes was not a factor in developing a subsequent skin cancer. DR. ALAM

ELSEVIER GLOBAL MEDICAL NEWS

SAN FRANCISCO — Vulvar granular cell tumors are biologically indolent lesions that may progress clinically over a decade or longer and most often occur in black patients, according to a recent review.

Of 16 granular cell tumors of the vulva that were surgically removed, 7 had positive margins, and only 1 progressed to a size requiring reexcision after 14 years, Dr. John A. Papalas and his associates reported at the annual meeting of the American Society of Dermatopathology. None of the tumors at the time of initial excision met histological criteria for malignancy.

The 16 lesions occurred on 12 patients (including 10 black patients) who were seen at Duke University, Durham, N.C. The patients' average age was 46 years.

The question of whether to reexcise a vulvar granular cell tumor with positive margins should be considered carefully because of the greater morbidity, compared with excisions in other areas of the body, noted Dr. Papalas of Duke University.

In a previous report on 20 patients with vulvar granular cell tumors, investigators suggested obtaining wide negative surgical margins (up to 2 cm), but the study provided follow-up data on only 1 patient and did not report the surgical margin resection status, he pointed out (Am. J. Obstet. Gynecol. 1995;173:1710-3).

Given the findings of the current study, which show that these tumors rarely recurred regardless of surgical margin status, "a 2-cm margin of a benign tumor on the vulva seems a bit excessive," one physician in the audience commented.

Patients with multiple vulvar granular cell tumors rarely have been reported in the literature. Three patients in the current series had multiple vulvar granular cell tumors and additional granular cell tumors in another body area. Another patient had a single vulvar tumor and an isolated lesion in another body area. Eight patients had a single granular cell tumor on the vulva alone. Extravulvar sites included the groin, perirectal area, buttock, esophagus, neck, buccal mucosa, and scalp.

Of the three patients with multiple vulvar granular cell tumors, only one presented with multiple vulvar lesions—a 50-year-old woman (just 2 years older than the average age), Dr. Papalas noted. Two other patients with an average age of 30 years presented with a single vulvar granular cell tumor and later progressed to multiple vulvar lesions over a 14-year period after the initial excision.

The surgical note or pathology report should precisely document the tumor location in order to accurately track recurrence or progression, he advised. Simply saying the tumor is on the "vulva" is not good enough, because the vulva is an anatomically complex region. The most common location of lesions in the current series was the labia majora, for 7 of 16 tumors.

Grossly, the tumors in this series either were well-circumscribed tan/white nodules or infiltrative masses, with an average tumor size of 2 cm.

A granular cell tumor is a Schwann cell-derived neoplasm that can occur throughout the body. Most involve the skin and soft tissue. Biopsies classically show tumor cells with abundant, pink granular cytoplasm and monomorphic, bland nuclei, though they can be mistaken for other lesions. "They're not always a slam-dunk diagnosis," Dr. Papalas said.

Granular cell tumors appear to be the most common peripheral nerve sheath-derived neoplasm in the vulva, he added.

SAN FRANCISCO — Vulvar granular cell tumors are biologically indolent lesions that may progress clinically over a decade or longer and most often occur in black patients, according to a recent review.

Of 16 granular cell tumors of the vulva that were surgically removed, 7 had positive margins, and only 1 progressed to a size requiring reexcision after 14 years, Dr. John A. Papalas and his associates reported at the annual meeting of the American Society of Dermatopathology. None of the tumors at the time of initial excision met histological criteria for malignancy.

The 16 lesions occurred on 12 patients (including 10 black patients) who were seen at Duke University, Durham, N.C. The patients' average age was 46 years.

The question of whether to reexcise a vulvar granular cell tumor with positive margins should be considered carefully because of the greater morbidity, compared with excisions in other areas of the body, noted Dr. Papalas of Duke University.

In a previous report on 20 patients with vulvar granular cell tumors, investigators suggested obtaining wide negative surgical margins (up to 2 cm), but the study provided follow-up data on only 1 patient and did not report the surgical margin resection status, he pointed out (Am. J. Obstet. Gynecol. 1995;173:1710-3).

Given the findings of the current study, which show that these tumors rarely recurred regardless of surgical margin status, "a 2-cm margin of a benign tumor on the vulva seems a bit excessive," one physician in the audience commented.

Patients with multiple vulvar granular cell tumors rarely have been reported in the literature. Three patients in the current series had multiple vulvar granular cell tumors and additional granular cell tumors in another body area. Another patient had a single vulvar tumor and an isolated lesion in another body area. Eight patients had a single granular cell tumor on the vulva alone. Extravulvar sites included the groin, perirectal area, buttock, esophagus, neck, buccal mucosa, and scalp.

Of the three patients with multiple vulvar granular cell tumors, only one presented with multiple vulvar lesions—a 50-year-old woman (just 2 years older than the average age), Dr. Papalas noted. Two other patients with an average age of 30 years presented with a single vulvar granular cell tumor and later progressed to multiple vulvar lesions over a 14-year period after the initial excision.

The surgical note or pathology report should precisely document the tumor location in order to accurately track recurrence or progression, he advised. Simply saying the tumor is on the "vulva" is not good enough, because the vulva is an anatomically complex region. The most common location of lesions in the current series was the labia majora, for 7 of 16 tumors.

Grossly, the tumors in this series either were well-circumscribed tan/white nodules or infiltrative masses, with an average tumor size of 2 cm.

A granular cell tumor is a Schwann cell-derived neoplasm that can occur throughout the body. Most involve the skin and soft tissue. Biopsies classically show tumor cells with abundant, pink granular cytoplasm and monomorphic, bland nuclei, though they can be mistaken for other lesions. "They're not always a slam-dunk diagnosis," Dr. Papalas said.

Granular cell tumors appear to be the most common peripheral nerve sheath-derived neoplasm in the vulva, he added.

SAN FRANCISCO — Vulvar granular cell tumors are biologically indolent lesions that may progress clinically over a decade or longer and most often occur in black patients, according to a recent review.

Of 16 granular cell tumors of the vulva that were surgically removed, 7 had positive margins, and only 1 progressed to a size requiring reexcision after 14 years, Dr. John A. Papalas and his associates reported at the annual meeting of the American Society of Dermatopathology. None of the tumors at the time of initial excision met histological criteria for malignancy.

The 16 lesions occurred on 12 patients (including 10 black patients) who were seen at Duke University, Durham, N.C. The patients' average age was 46 years.

The question of whether to reexcise a vulvar granular cell tumor with positive margins should be considered carefully because of the greater morbidity, compared with excisions in other areas of the body, noted Dr. Papalas of Duke University.

In a previous report on 20 patients with vulvar granular cell tumors, investigators suggested obtaining wide negative surgical margins (up to 2 cm), but the study provided follow-up data on only 1 patient and did not report the surgical margin resection status, he pointed out (Am. J. Obstet. Gynecol. 1995;173:1710-3).

Given the findings of the current study, which show that these tumors rarely recurred regardless of surgical margin status, "a 2-cm margin of a benign tumor on the vulva seems a bit excessive," one physician in the audience commented.

Patients with multiple vulvar granular cell tumors rarely have been reported in the literature. Three patients in the current series had multiple vulvar granular cell tumors and additional granular cell tumors in another body area. Another patient had a single vulvar tumor and an isolated lesion in another body area. Eight patients had a single granular cell tumor on the vulva alone. Extravulvar sites included the groin, perirectal area, buttock, esophagus, neck, buccal mucosa, and scalp.

Of the three patients with multiple vulvar granular cell tumors, only one presented with multiple vulvar lesions—a 50-year-old woman (just 2 years older than the average age), Dr. Papalas noted. Two other patients with an average age of 30 years presented with a single vulvar granular cell tumor and later progressed to multiple vulvar lesions over a 14-year period after the initial excision.

The surgical note or pathology report should precisely document the tumor location in order to accurately track recurrence or progression, he advised. Simply saying the tumor is on the "vulva" is not good enough, because the vulva is an anatomically complex region. The most common location of lesions in the current series was the labia majora, for 7 of 16 tumors.

Grossly, the tumors in this series either were well-circumscribed tan/white nodules or infiltrative masses, with an average tumor size of 2 cm.

A granular cell tumor is a Schwann cell-derived neoplasm that can occur throughout the body. Most involve the skin and soft tissue. Biopsies classically show tumor cells with abundant, pink granular cytoplasm and monomorphic, bland nuclei, though they can be mistaken for other lesions. "They're not always a slam-dunk diagnosis," Dr. Papalas said.

Granular cell tumors appear to be the most common peripheral nerve sheath-derived neoplasm in the vulva, he added.

Case Report
A 69-year-old man with a medical history of psoriasis and hypertension presented with an incidental finding of multiple asymptomatic, noncompressible, blue lesions over his arms, chest, and back. The lesions were present since childhood and had never been subject to a workup. He had no history of gastrointestinal bleeding and no known family history of similar lesions. His medications included amlodipine besylate, efalizumab, and valsartan. Physical examination revealed multiple nontender, blue, subcutaneous nodules that were 1 to 2 cm in diameter and located on the bilateral arms, chest, and back (Figure 1). A punch biopsy was performed from the chest lesions. Histopathologic examination revealed dilated vascular channels (Figure 2) that were positive for endothelial factor VIII and CD34 and surrounded by glomus cells positive for smooth muscle actin (Figure 3). The diagnosis of glomangioma was made and no further treatment was indicated.

Comment
Glomangiomas are benign localized tumors of the skin characterized by abnormal, smooth muscle–like glomus cells.1 In 1924, Masson2 described the neuromyoarterial glomus, which he later renamed the neurovascular glomus, and its tumors. The term glomangioma was coined by Bailey3 in 1935 and is currently applied to lesions with a wide vascular lumen, which are most commonly found in patients with multiple tumors.4 Glomus tumors arise from modified smooth muscle cells normally found in specialized arteriovenous shunts present in acral sites, especially the fingertips. This location reflects their function, as the arteriovenous anastomoses of these areas, also known as the Sucquet-Hoyer canals, are involved in temperature regulation. Sucquet-Hoyer canals are lined with endothelial cells, contain several layers of glomus cells in their walls, and connect afferent arterioles to efferent venules.5 Glomus tumors are thought to be hamartomas6 and account for 1% to 2% of all soft tissue tumors.5 There are 2 forms of glomus tumors, with the more common solitary variant accounting for 90% of cases and a more rare multiple variant, termed glomangioma, accounting for 10% of cases.7 The tumors of the solitary variant are small, painful, purple nodules with predilection for acral areas of the extremities, especially the nail beds of the fingers and toes.8 Aching pain, well-localized tenderness, and temperature sensitivity are the characteristic triad of signs and symptoms.5 They typically are less than 1 cm in diameter.8 In contrast, multiple glomus tumors are characterized as glomangiomas because of the angiomatous appearance of the lesions. Glomangiomas often appear during childhood as small bluish nodules situated deep in the dermis, widely scattered over the skin surface. They are rarely subungual and are less likely to be painful.8 Glomangiomas have a predilection for the upper extremities and occasionally are found on the lower extremities, head, and back. They may be slightly larger and less well-circumscribed than solitary glomus tumors.5 An autosomal dominant inheritance pattern has been described for glomus tumors, with some types being mapped to band 11q23.6 Familial cases have been reported with incomplete penetrance and variable expression.7 Glomangiomas have a male predominance, while females more frequently (in 70% of cases) are found to have solitary glomus tumors.5 Histopathologically, glomus tumors contain dilated vascular channels surrounded by glomus cells. The glomus cells are monomorphic round or polygonal cells with plump nuclei and scant eosinophilic cytoplasm. They are positive for smooth muscle actin, while vascular endothelium is positive for factor VIII and CD34.9 Choosing the appropriate treatment regimen for glomus tumors and glomangiomas should be individualized to the patient and guided by the clinical presentation. Treatment is not always indicated, particularly in asymptomatic cases of glomangioma. Surgical intervention, when needed, typically is excision with primary closure. Laser treatment, electromagnetic radiation, and sclerotherapy also have been used.5 Blue Rubber Bleb Nevus Syndrome—It is important to distinguish glomangioma from blue rubber bleb nevus syndrome (BRBNS), which is associated with venous malformations on both the skin and gastrointestinal tract. The BRBNS venous malformations of the gastrointestinal tract can be associated with clinically significant gastrointestinal bleeding.10 Lesions of BRBNS can be macular, papular, or nodular, and usually are multiple, varying in diameter from a few millimeters to several centimeters. The cutaneous lesions usually are asymptomatic and the overlying skin may show increased sweating. These lesions may appear at birth or in early childhood, and they tend to increase in size and frequency with age. Although they may occur anywhere, they are principally located on the upper limbs, trunk, and perineum. Acral lesions are unusual and the lesions have no evidence of malignant change.11 Cutaneous lesions of BRBNS are blue, soft, and nipplelike, easily compressing and refilling slowly.12 On the other hand, glomangiomas are noted for a distinct raised, often hyperkeratotic, cobblestonelike appearance, and could not be completely emptied by compression.13 Glomangiomas generally do not extend into deep structures.14 Histologically, glomangiomas contain clusters of dilated vascular channels lined by a thin layer of endothelial cells in the dermis or subcutaneous fat. The walls are a fibrous stroma, occasionally containing smooth muscle.12 Dilated vascular channels lined by endothelial cells are characteristic of both diseases. Therefore, biopsy results confirming the presence of glomus cells lining the dilated vascular channels characterize glomangiomas.10 back to top

Case Report
A 69-year-old man with a medical history of psoriasis and hypertension presented with an incidental finding of multiple asymptomatic, noncompressible, blue lesions over his arms, chest, and back. The lesions were present since childhood and had never been subject to a workup. He had no history of gastrointestinal bleeding and no known family history of similar lesions. His medications included amlodipine besylate, efalizumab, and valsartan. Physical examination revealed multiple nontender, blue, subcutaneous nodules that were 1 to 2 cm in diameter and located on the bilateral arms, chest, and back (Figure 1). A punch biopsy was performed from the chest lesions. Histopathologic examination revealed dilated vascular channels (Figure 2) that were positive for endothelial factor VIII and CD34 and surrounded by glomus cells positive for smooth muscle actin (Figure 3). The diagnosis of glomangioma was made and no further treatment was indicated.

Comment
Glomangiomas are benign localized tumors of the skin characterized by abnormal, smooth muscle–like glomus cells.1 In 1924, Masson2 described the neuromyoarterial glomus, which he later renamed the neurovascular glomus, and its tumors. The term glomangioma was coined by Bailey3 in 1935 and is currently applied to lesions with a wide vascular lumen, which are most commonly found in patients with multiple tumors.4 Glomus tumors arise from modified smooth muscle cells normally found in specialized arteriovenous shunts present in acral sites, especially the fingertips. This location reflects their function, as the arteriovenous anastomoses of these areas, also known as the Sucquet-Hoyer canals, are involved in temperature regulation. Sucquet-Hoyer canals are lined with endothelial cells, contain several layers of glomus cells in their walls, and connect afferent arterioles to efferent venules.5 Glomus tumors are thought to be hamartomas6 and account for 1% to 2% of all soft tissue tumors.5 There are 2 forms of glomus tumors, with the more common solitary variant accounting for 90% of cases and a more rare multiple variant, termed glomangioma, accounting for 10% of cases.7 The tumors of the solitary variant are small, painful, purple nodules with predilection for acral areas of the extremities, especially the nail beds of the fingers and toes.8 Aching pain, well-localized tenderness, and temperature sensitivity are the characteristic triad of signs and symptoms.5 They typically are less than 1 cm in diameter.8 In contrast, multiple glomus tumors are characterized as glomangiomas because of the angiomatous appearance of the lesions. Glomangiomas often appear during childhood as small bluish nodules situated deep in the dermis, widely scattered over the skin surface. They are rarely subungual and are less likely to be painful.8 Glomangiomas have a predilection for the upper extremities and occasionally are found on the lower extremities, head, and back. They may be slightly larger and less well-circumscribed than solitary glomus tumors.5 An autosomal dominant inheritance pattern has been described for glomus tumors, with some types being mapped to band 11q23.6 Familial cases have been reported with incomplete penetrance and variable expression.7 Glomangiomas have a male predominance, while females more frequently (in 70% of cases) are found to have solitary glomus tumors.5 Histopathologically, glomus tumors contain dilated vascular channels surrounded by glomus cells. The glomus cells are monomorphic round or polygonal cells with plump nuclei and scant eosinophilic cytoplasm. They are positive for smooth muscle actin, while vascular endothelium is positive for factor VIII and CD34.9 Choosing the appropriate treatment regimen for glomus tumors and glomangiomas should be individualized to the patient and guided by the clinical presentation. Treatment is not always indicated, particularly in asymptomatic cases of glomangioma. Surgical intervention, when needed, typically is excision with primary closure. Laser treatment, electromagnetic radiation, and sclerotherapy also have been used.5 Blue Rubber Bleb Nevus Syndrome—It is important to distinguish glomangioma from blue rubber bleb nevus syndrome (BRBNS), which is associated with venous malformations on both the skin and gastrointestinal tract. The BRBNS venous malformations of the gastrointestinal tract can be associated with clinically significant gastrointestinal bleeding.10 Lesions of BRBNS can be macular, papular, or nodular, and usually are multiple, varying in diameter from a few millimeters to several centimeters. The cutaneous lesions usually are asymptomatic and the overlying skin may show increased sweating. These lesions may appear at birth or in early childhood, and they tend to increase in size and frequency with age. Although they may occur anywhere, they are principally located on the upper limbs, trunk, and perineum. Acral lesions are unusual and the lesions have no evidence of malignant change.11 Cutaneous lesions of BRBNS are blue, soft, and nipplelike, easily compressing and refilling slowly.12 On the other hand, glomangiomas are noted for a distinct raised, often hyperkeratotic, cobblestonelike appearance, and could not be completely emptied by compression.13 Glomangiomas generally do not extend into deep structures.14 Histologically, glomangiomas contain clusters of dilated vascular channels lined by a thin layer of endothelial cells in the dermis or subcutaneous fat. The walls are a fibrous stroma, occasionally containing smooth muscle.12 Dilated vascular channels lined by endothelial cells are characteristic of both diseases. Therefore, biopsy results confirming the presence of glomus cells lining the dilated vascular channels characterize glomangiomas.10 back to top

Case Report
A 69-year-old man with a medical history of psoriasis and hypertension presented with an incidental finding of multiple asymptomatic, noncompressible, blue lesions over his arms, chest, and back. The lesions were present since childhood and had never been subject to a workup. He had no history of gastrointestinal bleeding and no known family history of similar lesions. His medications included amlodipine besylate, efalizumab, and valsartan. Physical examination revealed multiple nontender, blue, subcutaneous nodules that were 1 to 2 cm in diameter and located on the bilateral arms, chest, and back (Figure 1). A punch biopsy was performed from the chest lesions. Histopathologic examination revealed dilated vascular channels (Figure 2) that were positive for endothelial factor VIII and CD34 and surrounded by glomus cells positive for smooth muscle actin (Figure 3). The diagnosis of glomangioma was made and no further treatment was indicated.

Comment
Glomangiomas are benign localized tumors of the skin characterized by abnormal, smooth muscle–like glomus cells.1 In 1924, Masson2 described the neuromyoarterial glomus, which he later renamed the neurovascular glomus, and its tumors. The term glomangioma was coined by Bailey3 in 1935 and is currently applied to lesions with a wide vascular lumen, which are most commonly found in patients with multiple tumors.4 Glomus tumors arise from modified smooth muscle cells normally found in specialized arteriovenous shunts present in acral sites, especially the fingertips. This location reflects their function, as the arteriovenous anastomoses of these areas, also known as the Sucquet-Hoyer canals, are involved in temperature regulation. Sucquet-Hoyer canals are lined with endothelial cells, contain several layers of glomus cells in their walls, and connect afferent arterioles to efferent venules.5 Glomus tumors are thought to be hamartomas6 and account for 1% to 2% of all soft tissue tumors.5 There are 2 forms of glomus tumors, with the more common solitary variant accounting for 90% of cases and a more rare multiple variant, termed glomangioma, accounting for 10% of cases.7 The tumors of the solitary variant are small, painful, purple nodules with predilection for acral areas of the extremities, especially the nail beds of the fingers and toes.8 Aching pain, well-localized tenderness, and temperature sensitivity are the characteristic triad of signs and symptoms.5 They typically are less than 1 cm in diameter.8 In contrast, multiple glomus tumors are characterized as glomangiomas because of the angiomatous appearance of the lesions. Glomangiomas often appear during childhood as small bluish nodules situated deep in the dermis, widely scattered over the skin surface. They are rarely subungual and are less likely to be painful.8 Glomangiomas have a predilection for the upper extremities and occasionally are found on the lower extremities, head, and back. They may be slightly larger and less well-circumscribed than solitary glomus tumors.5 An autosomal dominant inheritance pattern has been described for glomus tumors, with some types being mapped to band 11q23.6 Familial cases have been reported with incomplete penetrance and variable expression.7 Glomangiomas have a male predominance, while females more frequently (in 70% of cases) are found to have solitary glomus tumors.5 Histopathologically, glomus tumors contain dilated vascular channels surrounded by glomus cells. The glomus cells are monomorphic round or polygonal cells with plump nuclei and scant eosinophilic cytoplasm. They are positive for smooth muscle actin, while vascular endothelium is positive for factor VIII and CD34.9 Choosing the appropriate treatment regimen for glomus tumors and glomangiomas should be individualized to the patient and guided by the clinical presentation. Treatment is not always indicated, particularly in asymptomatic cases of glomangioma. Surgical intervention, when needed, typically is excision with primary closure. Laser treatment, electromagnetic radiation, and sclerotherapy also have been used.5 Blue Rubber Bleb Nevus Syndrome—It is important to distinguish glomangioma from blue rubber bleb nevus syndrome (BRBNS), which is associated with venous malformations on both the skin and gastrointestinal tract. The BRBNS venous malformations of the gastrointestinal tract can be associated with clinically significant gastrointestinal bleeding.10 Lesions of BRBNS can be macular, papular, or nodular, and usually are multiple, varying in diameter from a few millimeters to several centimeters. The cutaneous lesions usually are asymptomatic and the overlying skin may show increased sweating. These lesions may appear at birth or in early childhood, and they tend to increase in size and frequency with age. Although they may occur anywhere, they are principally located on the upper limbs, trunk, and perineum. Acral lesions are unusual and the lesions have no evidence of malignant change.11 Cutaneous lesions of BRBNS are blue, soft, and nipplelike, easily compressing and refilling slowly.12 On the other hand, glomangiomas are noted for a distinct raised, often hyperkeratotic, cobblestonelike appearance, and could not be completely emptied by compression.13 Glomangiomas generally do not extend into deep structures.14 Histologically, glomangiomas contain clusters of dilated vascular channels lined by a thin layer of endothelial cells in the dermis or subcutaneous fat. The walls are a fibrous stroma, occasionally containing smooth muscle.12 Dilated vascular channels lined by endothelial cells are characteristic of both diseases. Therefore, biopsy results confirming the presence of glomus cells lining the dilated vascular channels characterize glomangiomas.10 back to top

ORLANDO — Reviewing the original biopsy slides of patients before they undergo Mohs surgery could result in a change of diagnosis, which in some cases could avert unnecessary surgery, according to Dr. Suzy T. Butler.

In a retrospective study of 3,345 patients, a second review of the original biopsy slide resulted in 74 changed diagnoses. Of these, 45 patients had a change in their management and 25 avoided an unnecessary surgery, Dr. Butler said at the annual meeting of the American Society for Dermatologic Surgery. The study reviewed all patients referred to the cutaneous oncology unit for Mohs surgery at St. Louis University from January 2003 to March 2007.

In one case, a 76-year-old white female presented to her dermatologist with a pink papule on her right cheek that had been previously treated with liquid nitrogen. A shaved biopsy showed an atypical spindle cell proliferation that was read as a desmoplastic malignant melanoma.

A review of the biopsy slides, however, diagnosed the patient as having dermal scar, said Dr. Butler of St. Louis University. Because of this discrepancy, additional biopsies were performed. These confirmed the diagnosis of scar. An s100 stain showed a few spindle cells in the dermis. Surgery was cancelled, and close observation was planned.

In another case, a 74-year-old white male presented with a 1-year history of pink scaly plaques at the suprapubic area. A punch biopsy was originally read as superficial spreading melanoma in situ.

A review of the biopsy before surgery, however, suggested extramammary Paget disease, which was confirmed with additional biopsies. The patient underwent "slow Mohs" surgery with permanent section histology, as well as a thorough malignancy work-up that was negative.

"These cases illustrate how second-opinion review of histopathology before treatment can either avoid potentially disfiguring, unnecessary surgery or direct a different surgical approach and guide the need for other testing," said Dr. Butler.

In addition to recording the number of cases in which the diagnosis changed, the investigators noted how the diagnosis changed and then reviewed the patient's chart to see how that change affected the patient's management. They also recorded the board certification of the original pathologist. Nearly half (48%) of the slides that were rediagnosed had been read by certified dermatopathologists, Dr. Butler said.

The most common change in diagnosis was from one malignant tumor to another in 43% of the patients. Most commonly, a basal cell carcinoma (BCC) diagnosis changed to squamous cell carcinoma (SCC), or a melanoma went from in situ to invasive or vice versa, Dr. Butler said.

The next most common change in diagnosis was from malignant to benign in 36% of the patients. This was often a seborrheic keratosis or a verruca vulgaris being misdiagnosed as SCC.

BCC was most likely to be misdiagnosed, followed by SCC, and then by melanoma and melanoma in situ, Dr. Butler noted. Seventeen percent of discordant diagnoses involved melanoma and melanoma in situ.

"Misdiagnoses involving basal cells are likely related to their high representation in our population, as opposed to any diagnostic challenge," she said. "On the flip side, considering the small proportion of total tumors that melanoma and melanomas in situ represent in our population, they comprise a surprisingly substantial proportion of the misdiagnosed tumors."

She suggested that the diagnoses of melanoma or melanoma in situ might be the most cost-effective diseases to target with second-opinion review.

The most common change in patient management was cancellation of surgery in 25 patients. The planned surgical approach was changed in another 10 patients, and 1 patient had to be scheduled for surgery as a result of the second biopsy reading, Dr. Butler said.

The cost of taking a second look at biopsy slides is considerable, however. "We did a cost analysis and found that the estimated cost of reviewing the biopsy slides would be approximately $93,000 a year at our university based on the number of slides we look at per year. That is significant, but it has to be weighed against the other benefits," she said.

Surgeons gain much useful information regarding the nature of the tumor, particularly useful when there are deeply infiltrating, aggressive tumors or in cases of perineural involvement, said Dr. Butler, who disclosed having no conflicts of interest relevant to her presentation.

Melanoma and melanoma in situ might be the most cost-effective diseases to target with second-opinion review. DR. BUTLER

ORLANDO — Reviewing the original biopsy slides of patients before they undergo Mohs surgery could result in a change of diagnosis, which in some cases could avert unnecessary surgery, according to Dr. Suzy T. Butler.

In a retrospective study of 3,345 patients, a second review of the original biopsy slide resulted in 74 changed diagnoses. Of these, 45 patients had a change in their management and 25 avoided an unnecessary surgery, Dr. Butler said at the annual meeting of the American Society for Dermatologic Surgery. The study reviewed all patients referred to the cutaneous oncology unit for Mohs surgery at St. Louis University from January 2003 to March 2007.

In one case, a 76-year-old white female presented to her dermatologist with a pink papule on her right cheek that had been previously treated with liquid nitrogen. A shaved biopsy showed an atypical spindle cell proliferation that was read as a desmoplastic malignant melanoma.

A review of the biopsy slides, however, diagnosed the patient as having dermal scar, said Dr. Butler of St. Louis University. Because of this discrepancy, additional biopsies were performed. These confirmed the diagnosis of scar. An s100 stain showed a few spindle cells in the dermis. Surgery was cancelled, and close observation was planned.

In another case, a 74-year-old white male presented with a 1-year history of pink scaly plaques at the suprapubic area. A punch biopsy was originally read as superficial spreading melanoma in situ.

A review of the biopsy before surgery, however, suggested extramammary Paget disease, which was confirmed with additional biopsies. The patient underwent "slow Mohs" surgery with permanent section histology, as well as a thorough malignancy work-up that was negative.

"These cases illustrate how second-opinion review of histopathology before treatment can either avoid potentially disfiguring, unnecessary surgery or direct a different surgical approach and guide the need for other testing," said Dr. Butler.

In addition to recording the number of cases in which the diagnosis changed, the investigators noted how the diagnosis changed and then reviewed the patient's chart to see how that change affected the patient's management. They also recorded the board certification of the original pathologist. Nearly half (48%) of the slides that were rediagnosed had been read by certified dermatopathologists, Dr. Butler said.

The most common change in diagnosis was from one malignant tumor to another in 43% of the patients. Most commonly, a basal cell carcinoma (BCC) diagnosis changed to squamous cell carcinoma (SCC), or a melanoma went from in situ to invasive or vice versa, Dr. Butler said.

The next most common change in diagnosis was from malignant to benign in 36% of the patients. This was often a seborrheic keratosis or a verruca vulgaris being misdiagnosed as SCC.

BCC was most likely to be misdiagnosed, followed by SCC, and then by melanoma and melanoma in situ, Dr. Butler noted. Seventeen percent of discordant diagnoses involved melanoma and melanoma in situ.

"Misdiagnoses involving basal cells are likely related to their high representation in our population, as opposed to any diagnostic challenge," she said. "On the flip side, considering the small proportion of total tumors that melanoma and melanomas in situ represent in our population, they comprise a surprisingly substantial proportion of the misdiagnosed tumors."

She suggested that the diagnoses of melanoma or melanoma in situ might be the most cost-effective diseases to target with second-opinion review.

The most common change in patient management was cancellation of surgery in 25 patients. The planned surgical approach was changed in another 10 patients, and 1 patient had to be scheduled for surgery as a result of the second biopsy reading, Dr. Butler said.

The cost of taking a second look at biopsy slides is considerable, however. "We did a cost analysis and found that the estimated cost of reviewing the biopsy slides would be approximately $93,000 a year at our university based on the number of slides we look at per year. That is significant, but it has to be weighed against the other benefits," she said.

Surgeons gain much useful information regarding the nature of the tumor, particularly useful when there are deeply infiltrating, aggressive tumors or in cases of perineural involvement, said Dr. Butler, who disclosed having no conflicts of interest relevant to her presentation.

Melanoma and melanoma in situ might be the most cost-effective diseases to target with second-opinion review. DR. BUTLER

ORLANDO — Reviewing the original biopsy slides of patients before they undergo Mohs surgery could result in a change of diagnosis, which in some cases could avert unnecessary surgery, according to Dr. Suzy T. Butler.

In a retrospective study of 3,345 patients, a second review of the original biopsy slide resulted in 74 changed diagnoses. Of these, 45 patients had a change in their management and 25 avoided an unnecessary surgery, Dr. Butler said at the annual meeting of the American Society for Dermatologic Surgery. The study reviewed all patients referred to the cutaneous oncology unit for Mohs surgery at St. Louis University from January 2003 to March 2007.

In one case, a 76-year-old white female presented to her dermatologist with a pink papule on her right cheek that had been previously treated with liquid nitrogen. A shaved biopsy showed an atypical spindle cell proliferation that was read as a desmoplastic malignant melanoma.

A review of the biopsy slides, however, diagnosed the patient as having dermal scar, said Dr. Butler of St. Louis University. Because of this discrepancy, additional biopsies were performed. These confirmed the diagnosis of scar. An s100 stain showed a few spindle cells in the dermis. Surgery was cancelled, and close observation was planned.

In another case, a 74-year-old white male presented with a 1-year history of pink scaly plaques at the suprapubic area. A punch biopsy was originally read as superficial spreading melanoma in situ.

A review of the biopsy before surgery, however, suggested extramammary Paget disease, which was confirmed with additional biopsies. The patient underwent "slow Mohs" surgery with permanent section histology, as well as a thorough malignancy work-up that was negative.

"These cases illustrate how second-opinion review of histopathology before treatment can either avoid potentially disfiguring, unnecessary surgery or direct a different surgical approach and guide the need for other testing," said Dr. Butler.

In addition to recording the number of cases in which the diagnosis changed, the investigators noted how the diagnosis changed and then reviewed the patient's chart to see how that change affected the patient's management. They also recorded the board certification of the original pathologist. Nearly half (48%) of the slides that were rediagnosed had been read by certified dermatopathologists, Dr. Butler said.

The most common change in diagnosis was from one malignant tumor to another in 43% of the patients. Most commonly, a basal cell carcinoma (BCC) diagnosis changed to squamous cell carcinoma (SCC), or a melanoma went from in situ to invasive or vice versa, Dr. Butler said.

The next most common change in diagnosis was from malignant to benign in 36% of the patients. This was often a seborrheic keratosis or a verruca vulgaris being misdiagnosed as SCC.

BCC was most likely to be misdiagnosed, followed by SCC, and then by melanoma and melanoma in situ, Dr. Butler noted. Seventeen percent of discordant diagnoses involved melanoma and melanoma in situ.

"Misdiagnoses involving basal cells are likely related to their high representation in our population, as opposed to any diagnostic challenge," she said. "On the flip side, considering the small proportion of total tumors that melanoma and melanomas in situ represent in our population, they comprise a surprisingly substantial proportion of the misdiagnosed tumors."

She suggested that the diagnoses of melanoma or melanoma in situ might be the most cost-effective diseases to target with second-opinion review.

The most common change in patient management was cancellation of surgery in 25 patients. The planned surgical approach was changed in another 10 patients, and 1 patient had to be scheduled for surgery as a result of the second biopsy reading, Dr. Butler said.

The cost of taking a second look at biopsy slides is considerable, however. "We did a cost analysis and found that the estimated cost of reviewing the biopsy slides would be approximately $93,000 a year at our university based on the number of slides we look at per year. That is significant, but it has to be weighed against the other benefits," she said.

Surgeons gain much useful information regarding the nature of the tumor, particularly useful when there are deeply infiltrating, aggressive tumors or in cases of perineural involvement, said Dr. Butler, who disclosed having no conflicts of interest relevant to her presentation.

Melanoma and melanoma in situ might be the most cost-effective diseases to target with second-opinion review. DR. BUTLER