Malignant Melanoma

Refining Surgery for Malignant Melanoma
Sentinel node biopsy to preserve the lymph nodes

Jesse Green, PhD
Senior Director, Clinical Evaluation

A New Technique

Karin MacCardle was very concerned when a small mole she noticed turned out to be malignant melanoma. Karin was referred to Dr. Daniel Roses at NYU who scheduled surgery immediately. Until recently, Karin's operation would have been a two part procedure: a wide and deep excision of the melanoma site, and removal of clusters of nearby lymph nodes (complete regional lymphadenectomy) as a precaution against the spread of cancer. That's because the thickness of the melanoma (2.8 mm) placed it in a category where 1 out of 4 patients has metastasis to the regional nodes. Traditionally, such patients would often have had all their regional lymph nodes removed.

Thanks to a new technique called sentinel node biopsy, Dr. Roses did not have to perform a complete lymphadenectomy for Karin. Instead of extensive surgery to completely dissect all the regional lymph nodes, Karin had only one node removed.

The Sentinel Node
It was not known until recently that the metastasis of melanoma occurs initially through a single lymph node. Dr. Roses and his colleague Dr. Matthew Harris helped pave the way for this observation while studying patients with head and neck melanomas. They found that lymph node involvement consistently included the nodes immediately adjacent to the melanoma site, rarely skipping over these nodes to more distant ones. This observation led to less extensive dissections of lymph nodes in the head and neck region.

Until recently, most patients with lesions
thicker than 1 mm had a complete
regional lymphadenectomy.

Later research with radioisotopic imaging (lymphoscintigraphy) demonstrated that lymph draining from a melanoma site nearly always flowed first to a single node (the sentinel node) and that cancer cells rarely bypassed this node. If the sentinel node is free of melanoma, a surgeon can safely conclude that the lymph nodes further down the line are melanoma-free as well.

Tagging the Node

Translating the discovery of the sentinel node to clinical practice required a sure way to "tag" the sentinel node, so the surgeon could distinguish it unfailingly from the many lymph nodes surrounding it.

Elissa Kramer, MD, Associate Professor of Clinical Radiology at NYU, outlines the "tagging" process:

Three methods of identification are used at NYU to guarantee accurate detection of the sentinel node. First, several days before sugery, lymphoscintigraphy is used to map the lymph flow into the sentinel node and mark the skin above it. Second, just prior to surgery, a radioisotope is injected into the melanoma site. The radioactive isotope drains into the sentinel node, so that a gamma probe (a hand-held sensor attached to a geiger counter) can detect the node's location. Third, a blue dye is injected into the site of the melanoma which is carried by the lymphatics directly to the sentinel node. The arrival of this dye stains the sentinel node blue — which makes it clearly visible to the surgeon.

Dr. Roses credits Dr. Donald Morton, MD, Director of the John Wayne Cancer Institute, with the development of this technique. Dr. Roses is a principal investigator on a multicenter study of this sentinel node procedure, supported by the National Cancer Institute and directed by Dr. Morton.

Finding the Node

After the melanoma site is injected with both radioisotope and blue dye,

an incision is made in the skin above the sentinel node, identified by lymphoscintigraphy. The surgeon then inserts the gamma probe to detect radioactivity in the draining node, and identifies the "hot" sentinel node, which has the highest level of radioactivity. Next, the surgeon confirms that this is in fact the sentinel node by its blue color and removes it.

Surgeons who developed significant
refinements in lymph node surgery
now work to reserve the surgery for
only those patients who can benefit from it.

Analysis by the Pathologist
With the patient still in surgery, pathologists immediately begin an exacting and sophisticated microscopic examination of the sentinel node to search for any malignant cells. While waiting for the pathologic evaluation, the surgeon performs a wide and deep excision at the melanoma site. If the pathologist finds metastasis in the sentinel node, a complete lymphadenectomy is performed. In 3 out of 4 cases no metastasis is found and the patient goes home without further surgery.

"Analysis of the sentinel node for the presence of melanoma doesn't stop there. The lab processes and analyzes a series of slides for several days following surgery. Specialized immunological staining and other precise techniques enable the pathologist to detect tumor deposits consisting of as few as 5 to 10 malignant cells in the entire node — and achieve remarkable diagnostic accuracy."
— pathologist Johnathan Melamed, MD

If microscopic traces of melanoma are found, the patient must return for a lymphadenectomy.

In Karin's case, there were no signs of metastasis during or after surgery. Karin went home the day after surgery and is being followed with an outpatient evaluation every three months.

Sparing the Lymph Nodes
Dr. Roses, Dr. Harris, and their late colleague Dr. Stephen Gumport developed techniques which are now standard throughout the country for performing lymphadenectomy. According to Dr. Roses,

"We have modified these procedures to diminish morbidity both functionally and cosmetically. Nevertheless, we are glad to use the sentinel node biopsy to limit complete lymphadenectomy to only those patients who stand to benefit from it."

The Thick and Thin of Melanoma

An Interview with Daniel F. Roses, MD

Editor: Dr. Roses, what difference does the thickness of a patient's melanoma make?

Roses: Measuring thickness under a microscope provides insight into the possible progression of the cancer. Thick, late stage melanomas (greater than 4 mm) are far more likely to have spread while thin melanomas (less than 1 mm) usually have not, and therefore rarely require lymph node surgery.

Editor: Doesn't that leave a gap between 1 and 4 mm?

Roses: Yes, in that range, the benefits from lyphadenectomy are unclear. Out of every four patients with mid-range melanomas, one will have lymph node involvement but three will not.

Editor: In other words, three out of four don't need their lymph nodes removed. So, how do you decide what to do?

Roses: Traditionally, surgeons either removed all the regional lymph nodes from these patients or removed none and followed them carefully. The strategy of complete regional lymphadenectomy benefitted some patients who had nodal spread of the cancer, but many others underwent complete lymph node dissection only to find that their nodes had been cancer-free.

Editor: Will sentinel node biopsy change that?

Roses: Yes, because the surgeon learns the state of the lymph nodes before deciding to perform a complete regional lymphadenectomy. By testing just one lymph node we get the crucial data we need with a minimum of trauma to the patient. With the biopsy we are able to precisely target the patients who might benefit from lymphadenectomy and allow others to avoid the procedure.

With Melanoma, Every Step in Diagnosis and Treatment Counts

According to the Experts . . .

"Early recognition of melanoma saves lives. For small lesions, a new non-invasive technique called dermoscopy lets us see below the skin's surface and facilitates early detection." — Alfred Kopf, MD, Clinical Professor of Dermatology

"Exacting microscopic evaluation and measurement are critical since a difference of only a few millimeters in thickness can have significant implications for choice of therapy and the patient's prognosis." — Hideko Kamino, MD, Associate Professor of Dermatology and Surgical Pathology

"For patients with a high risk of recurrence, we use the most sophisticated and aggressive medical and surgical techniques to fight the disease, including high dosage interferon alpha-2b, the first biological therapy proven to increase survival." — Ruth Oratz, MD, Assistant Professor of Clinical Medicine

"Our first generation of anti-melanoma vaccines trigger the patient's own immune response to prevent recurrence. We are now working to improve the vaccine's ability to stimulate anti-melanoma immunity." — Jean-Claude Bystryn, MD, Director of the Melanoma Immunotherapy Clinic

Sentinel Node Biopsy

Benefits:

Reduced surgical risk and trauma
Shortened hospital stay
Preserved immune system function
Accelerated recovery
Increased patient satisfaction

Special Skills Required:

Nuclear Medicine —: lymphoscintigraphy
Surgery —: sentinel node identification and excision
Pathology —: immunostaining to identify micrometastases

For Further Information:

	*Refining Surgery for Malignant Melanoma* *Sentinel node biopsy to preserve the lymph nodes* Jesse Green, PhD Senior Director, Clinical Evaluation A New Technique Karin MacCardle was very concerned when a small mole she noticed turned out to be malignant melanoma. Karin was referred to Dr. Daniel Roses at NYU who scheduled surgery immediately. Until recently, Karin's operation would have been a two part procedure: a wide and deep excision of the melanoma site, and removal of clusters of nearby lymph nodes (complete regional lymphadenectomy) as a precaution against the spread of cancer. That's because the thickness of the melanoma (2.8 mm) placed it in a category where 1 out of 4 patients has metastasis to the regional nodes. Traditionally, such patients would often have had all their regional lymph nodes removed. Thanks to a new technique called sentinel node biopsy, Dr. Roses did not have to perform a complete lymphadenectomy for Karin. Instead of extensive surgery to completely dissect all the regional lymph nodes, Karin had only one node removed. The Sentinel Node It was not known until recently that the metastasis of melanoma occurs initially through a single lymph node. Dr. Roses and his colleague Dr. Matthew Harris helped pave the way for this observation while studying patients with head and neck melanomas. They found that lymph node involvement consistently included the nodes immediately adjacent to the melanoma site, rarely skipping over these nodes to more distant ones. This observation led to less extensive dissections of lymph nodes in the head and neck region.
	Until recently, most patients with lesions thicker than 1 mm had a complete regional lymphadenectomy.
	Later research with radioisotopic imaging (lymphoscintigraphy) demonstrated that lymph draining from a melanoma site nearly always flowed first to a single node (the sentinel node) and that cancer cells rarely bypassed this node. If the sentinel node is free of melanoma, a surgeon can safely conclude that the lymph nodes further down the line are melanoma-free as well. Tagging the Node Translating the discovery of the sentinel node to clinical practice required a sure way to "tag" the sentinel node, so the surgeon could distinguish it unfailingly from the many lymph nodes surrounding it. Elissa Kramer, MD, Associate Professor of Clinical Radiology at NYU, outlines the "tagging" process: Three methods of identification are used at NYU to guarantee accurate detection of the sentinel node. First, several days before sugery, lymphoscintigraphy is used to map the lymph flow into the sentinel node and mark the skin above it. Second, just prior to surgery, a radioisotope is injected into the melanoma site. The radioactive isotope drains into the sentinel node, so that a gamma probe (a hand-held sensor attached to a geiger counter) can detect the node's location. Third, a blue dye is injected into the site of the melanoma which is carried by the lymphatics directly to the sentinel node. The arrival of this dye stains the sentinel node blue — which makes it clearly visible to the surgeon. Dr. Roses credits Dr. Donald Morton, MD, Director of the John Wayne Cancer Institute, with the development of this technique. Dr. Roses is a principal investigator on a multicenter study of this sentinel node procedure, supported by the National Cancer Institute and directed by Dr. Morton. Finding the Node After the melanoma site is injected with both radioisotope and blue dye, an incision is made in the skin above the sentinel node, identified by lymphoscintigraphy. The surgeon then inserts the gamma probe to detect radioactivity in the draining node, and identifies the "hot" sentinel node, which has the highest level of radioactivity. Next, the surgeon confirms that this is in fact the sentinel node by its blue color and removes it.
	Surgeons who developed significant refinements in lymph node surgery now work to reserve the surgery for only those patients who can benefit from it.
	Analysis by the Pathologist With the patient still in surgery, pathologists immediately begin an exacting and sophisticated microscopic examination of the sentinel node to search for any malignant cells. While waiting for the pathologic evaluation, the surgeon performs a wide and deep excision at the melanoma site. If the pathologist finds metastasis in the sentinel node, a complete lymphadenectomy is performed. In 3 out of 4 cases no metastasis is found and the patient goes home without further surgery. "Analysis of the sentinel node for the presence of melanoma doesn't stop there. The lab processes and analyzes a series of slides for several days following surgery. Specialized immunological staining and other precise techniques enable the pathologist to detect tumor deposits consisting of as few as 5 to 10 malignant cells in the entire node — and achieve remarkable diagnostic accuracy." — pathologist Johnathan Melamed, MD If microscopic traces of melanoma are found, the patient must return for a lymphadenectomy. In Karin's case, there were no signs of metastasis during or after surgery. Karin went home the day after surgery and is being followed with an outpatient evaluation every three months. Sparing the Lymph Nodes Dr. Roses, Dr. Harris, and their late colleague Dr. Stephen Gumport developed techniques which are now standard throughout the country for performing lymphadenectomy. According to Dr. Roses, "We have modified these procedures to diminish morbidity both functionally and cosmetically. Nevertheless, we are glad to use the sentinel node biopsy to limit complete lymphadenectomy to only those patients who stand to benefit from it."
	The Thick and Thin of Melanoma An Interview with Daniel F. Roses, MD Editor: Dr. Roses, what difference does the thickness of a patient's melanoma make? Roses: Measuring thickness under a microscope provides insight into the possible progression of the cancer. Thick, late stage melanomas (greater than 4 mm) are far more likely to have spread while thin melanomas (less than 1 mm) usually have not, and therefore rarely require lymph node surgery. Editor: Doesn't that leave a gap between 1 and 4 mm? Roses: Yes, in that range, the benefits from lyphadenectomy are unclear. Out of every four patients with mid-range melanomas, one will have lymph node involvement but three will not. Editor: In other words, three out of four don't need their lymph nodes removed. So, how do you decide what to do? Roses: Traditionally, surgeons either removed all the regional lymph nodes from these patients or removed none and followed them carefully. The strategy of complete regional lymphadenectomy benefitted some patients who had nodal spread of the cancer, but many others underwent complete lymph node dissection only to find that their nodes had been cancer-free. Editor: Will sentinel node biopsy change that? Roses: Yes, because the surgeon learns the state of the lymph nodes before deciding to perform a complete regional lymphadenectomy. By testing just one lymph node we get the crucial data we need with a minimum of trauma to the patient. With the biopsy we are able to precisely target the patients who might benefit from lymphadenectomy and allow others to avoid the procedure. With Melanoma, Every Step in Diagnosis and Treatment Counts According to the Experts . . . "Early recognition of melanoma saves lives. For small lesions, a new non-invasive technique called dermoscopy lets us see below the skin's surface and facilitates early detection." — Alfred Kopf, MD, Clinical Professor of Dermatology "Exacting microscopic evaluation and measurement are critical since a difference of only a few millimeters in thickness can have significant implications for choice of therapy and the patient's prognosis." — Hideko Kamino, MD, Associate Professor of Dermatology and Surgical Pathology "For patients with a high risk of recurrence, we use the most sophisticated and aggressive medical and surgical techniques to fight the disease, including high dosage interferon alpha-2b, the first biological therapy proven to increase survival." — Ruth Oratz, MD, Assistant Professor of Clinical Medicine "Our first generation of anti-melanoma vaccines trigger the patient's own immune response to prevent recurrence. We are now working to improve the vaccine's ability to stimulate anti-melanoma immunity." — Jean-Claude Bystryn, MD, Director of the Melanoma Immunotherapy Clinic Sentinel Node Biopsy Benefits: Reduced surgical risk and trauma Shortened hospital stay Preserved immune system function Accelerated recovery Increased patient satisfaction Special Skills Required: Nuclear Medicine — lymphoscintigraphy Surgery — sentinel node identification and excision Pathology — immunostaining to identify micrometastases
	*For Further Information:* The Melanoma Research Foundation Accurate Nodal Staging of Malignant Melanoma Growth and Development of Primary Skin Melanomas: A Short Atlas The Merk Manual on Malignant Melanomas Webmaster: Neil Wintfeld, PhD © Copyright 1998 Department of Clinical Evaluation and Outcomes Research New York University Medical Center All rights reserved.