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Lymphatic Mapping in Melanoma
Alan M. Yahanda, M.D.,
Assistant Professor, Department of Surgery
Division of Surgical Oncology
The presence or absence of regional lymph node metastases
is the single most important prognostic factor in cutaneous
melanoma. This fact, taken together with the findings of the
Eastern Cooperative Oncology Group trial 1684, in which patients
with node-positive melanoma had an improvement of both disease-free
and overall survival if they received high-dose adjuvant Interferon
alpha, has stirred a new interest in identifying those patients
with early stage melanoma who harbor regional lymph node metastases
In the past, the only means of identifying patients with
regional nodal metastases was to perform a complete lymph
node dissection. These operations are associated with significant
morbidity, and in only a minority of patients, will lymph
node metastases be found. Thus, the majority of patients so
treated would be subjected to the morbidity and cost of a
surgery from which they will gain some prognostic information,
but will not derive any therapeutic benefit.
The Concept of Lymphatic Mapping
In the late 1980s, Morton from the John Wayne Cancer
Institute developed and described the technique of lymphatic
mapping in melanoma (3). This was based on the concept that
the dermal lymphatics for a given area of skin will drain
first to a specific lymph node or lymph nodes in a draining
lymphatic basin. This first draining node was termed the sentinel
node. Furthermore, geographically different regions of the
body would drain to distinct sentinel nodes (Figure
1). If one could identify and biopsy these sentinel nodes,
one could accurately assess whether or not metastases to the
lymph basin had occurred.
The sentinel lymph node is identified by a combination
of a blue dye and radiolabeled sulfur colloid. Both of these
agents are injected into the dermis around the melanoma or
melanoma-biopsy site, are taken up by the dermal lymphatic
channels, and flow to the sentinel node. A preoperative lymphoscintigram
is imperative in order to identify all nodal basins to which
the melanoma drains and to find any aberrant or unusual drainage
patterns (4). At the time of surgery, a hand-held gamma probe
is used to interrogate the lymphatic basin and to identify
areas of increased radioactivity. A small biopsy incision
is made over this area, and the sentinel node is found by
either identifying a blue lymph node visually, or a radioactive
node using the gamma probe. Once identified, the node is excised
and subjected to careful pathologic evaluation. Additional
sentinel nodes are found by either surveying the basin with
the gamma probe to identify any other areas with increased
radioactive counts or by finding a blue-stained lymph node.
Lymphatic Mapping Enables Selective Lymphadenectomy
Lymphatic mapping has become an invaluable technique
to identify those patients who harbor lymph node metastases.
By documenting which patients with early stage melanoma have
nodal disease, surgeons are now able to perform a selective
lymphadenectomy, that is, perform formal lymph node dissections
on only those patients who have documented metastatic disease,
while leaving intact the basins of those who do not (5,6).
In most series of lymphatic mapping, occult metastatic disease
is found in 15 to 21% of patients. Consequently, approximately
80% of patients will have their regional lymph nodes accurately
staged without being subjected to the morbidity of a formal
lymphadenectomy. Those patients found to have nodal metastases
undergo a formal lymphadenectomy and are referred for adjuvant
In their initial clinical report, Morton and colleagues
performed lymphatic mapping in 223 patients with early stage
melanoma. In all patients both the sentinel lymph node biopsy
and a formal lymphadenectomy were performed to document that
the sentinel node accurately reflected the status of the remainder
of the lymph nodes in the basin. Of the 40 lymphadenectomies
that contained metastatic disease, 38 contained tumor in the
sentinel node, for a false negative rate of 5% (3). Subsequently,
multiple institutions have reported their experiences with
this technique and have corroborated Morton's conclusions:
lymphatic mapping is a safe, accurate and reliable means of
staging the regional lymph node basins (3, 7-10).
The important question yet to be answered is if lymphatic
mapping and selective lymphadenectomy will have any impact
on patient survival. As of now, there are no reports which
have compared, in a prospective, randomized fashion, the survival
of patients managed with lymphatic mapping versus that of
patients managed with expectant observation of their nodal
basins. Theoretically, one would expect that early attention
to the lymph nodes and early institution of adjuvant therapy
would be advantageous, but we currently have no data to support
this belief. Several multi-institutional studies are being
conducted to address this question, but any meaningful data
will not be available for several more years.
Who is Eligible?
At the University of Michigan, and at most institutions
around the country, lymphatic mapping is offered to any
patient with a primary cutaneous melanoma with a Breslow depth
≥1 cm and with no clinical evidence of regional or distant
metastatic disease (11). Patients who have had a previous
wide local excision are not good candidates for subsequent
mapping. The lymphatic drainage of the skin surrounding the
excision scar may not be the same as the drainage of the excised
patch of skin where the melanoma had been located. Thus, any
sentinel lymph node removed may not be the correct sentinel
node for the melanoma. Accordingly, we emphasize that any
skin lesion suspicious for melanoma should be biopsied with
a narrow margin excision that is oriented parallel to the
direction of the dermal lymphatics. Furthermore, patients
with medical co-morbidities that make them poor candidates
for adjuvant interferon therapy may not be offered mapping,
as the results of the sentinel node biopsy would have no impact
on their subsequent treatment. In these cases, a discussion
of eligibility should be held between the medical oncologists
and surgeons in the setting of a multidisciplinary clinic.
If you would like to learn more about the technique of
lymphatic mapping, the Division of Surgical Oncology and the
Comprehensive Cancer Center offer a monthly preceptorship
that is open to all health care professionals. For more information,
contact Cancer AnswerLine™ 800-865-1125.
1. Morton DL, Ollila DW: Critical review of the sentinel
node hypothesis. Surgery 1999;126:815-819.
2. Kirkwood JM, Strawderman MH, Ernstoff MS, Smith TJ,
Borden EC, Blum RH: Interferon Alfa-2b adjuvant therapy of
high-risk resected cutaneous melanoma: the Eastern Cooperative
Oncology Group Trial EST 1684. J Clin Oncol 1996;14:7-17.
3. Morton DL, Wen D-R, Wond JH, et al: Technical details
of intraoperative lymphatic mapping for early stage melanoma.
Arch Surg 1992;127:392-399.
4. Thompson JF, Uren RF, Shaw HM, et al: Location of sentinel
lymph nodes in patients with cutaneous melanoma: new insights
into lymphatic anatomy. J Am Coll Surg 1999;189:195-206.
5. Ross MI, Reintgen DS, Balch CM: Selective lymphadenectomy:
emerging role for lymphatic mapping and sentinel node biopsy
in the management of early stage melanoma. Sem Surg Oncol
6. Glass LF, Fenske NA, Messina JL, et al: The role of
selective lymphadenectomy in the management of patients with
malignant melanoma. Dermatol Surg 1995;21:979-983.
7. Reintgen D, Cruse CW, Wells K, et al: The orderly progression
of melanoma nodal metastases. Ann Surg 1994;220:759-767.
8. Thompson JF, McCarthy WH, Bosch CM, et al: Sentinel
lymph node status as an indicator of the presence of metastatic
melanoma in regional lymph nodes. Melanoma Res 1995;5:255-260.
9. Haddad FF, Stall A, Messina J, Brobeil A, et al: The
progression of melanoma nodal metastasis is dependent of tumor
thickness of the primary lesion. Ann Surg Oncol 1999;6:144-149.
10. Gershenwald JE, Thompson W, Mansfield PF, et al: Multi-institutional
melanoma lymphatic mapping experience: the prognostic value
of sentinel lymph node status in 612 stage I and II melanoma
patients. J Clin Oncol 1999;17:976-983.
11. NCCN melanoma practice guidelines. Oncology 1998;12:153177.
Figure 1: Concept of lymphatic mapping: the dermal lymphatics
for every region of the skin will drain first to a specific
lymph node, the sentinel lymph node. Geographically distinct
regions of the skin will drain to distinct lymph nodes in
the regional lymphatic basin.
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