Sentinel lymph node biopsy is commonly applied as staging procedure of regional lymph nodes in patients with cutaneous melanoma. Dynamic lymphoscintigraphy defines the lymphatic pathways from a primary melanoma site and allows to identify the node receiving lymphatic drainage from the primary tumor, which is the sentinel lymph node. In rare cases, lymphoscintigraphy shows sites of lymphatic drainage in nonclassical basins never described in the past when lymphatic drainage was considered only according to the anatomical proximity of the tumor primary site. These peculiar sentinel nodes, so-called “uncommon/interval” nodes, must be surgically removed because they may contain micrometastatic disease and may be the only site of nodal involvement.
Sentinel lymph node biopsy (SLNB) is commonly applied as staging procedure of regional lymph nodes in patients with cutaneous melanoma. Dynamic lymphoscintigraphy defines the lymphatic pathways from a primary melanoma site and allows to identify the node receiving lymphatic drainage from the primary tumor, which is the sentinel lymph node [
At the National Cancer Institute of Naples, patients with a primary tumor thicker than 1 mm or at least Clark level IV-V, ulcerated or with ≥1 mitosis/mm2, without clinical evidence of nodal metastases, undergo SLNB. Prior to surgery, we perform clinical evaluation of all patients with liver ultrasound, chest X-ray, and lactate dehydrogenase to rule out the presence of distant metastases. Patients who had received a wide excision of the primary (more than 3 cm) or had undergone reconstruction with a cutaneous rotation flap are excluded, because the probable disruption of lymphatic drainage. Dynamic lymphoscintigraphy is performed 2–4 hours before surgery. A dose of 18 MBq 99mTechnetium-labelled colloidal albumin (nanocoll) colloid is injected intradermally around the tumor. Dynamic and planar images from different points of view are obtained, and the sentinel node “hot spot” is marked on the skin.
About 20 minutes before the surgical procedure, 1.0 mL of Patent Blue dye is injected intradermally around the primary scar. A hand-held gamma probe guides the identification of sentinel nodes, with correlation of radioactivity in vivo, ex vivo and in the operative field. Blue lymph nodes are excised as well any radioactive nodes that exhibit high level of radioactivity in the operative field. Serial sections of SN are analyzed by standard stain with hematoxylin and eosin (H&E) and immunohystochemical (IHC) staining with S-100 and HMB-45 antibodies. Patients with tumor- positive SN undergo complete lymph node dissection of the involved basin. Stage I-II melanoma patients were followed every three months for the first two years and every six months thereafter, with clinical evaluation, liver and lymph nodes ultrasound, serum biochemistry, and chest X-ray every six months. Computed tomography (CT) and fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) and bone scans are performed only in cases of clinical suspicion of distant extension or recidiva. The follow up for stage III patients is similar to stage I-II patients, but a total body CT or FDG PET scan is performed every year [
The inguinal nodes are considered the classical nodal basin in the lower extremities, the axillary nodes are typical basin for the upper extremities. Drainage is expected to occur to the nearest axillary or inguinal basin in patients with primary tumor sites in the torso. If a melanoma is located within 2.5 cm of the midline, the drainage can occur to either side or both sides and is not considered discordant. Similarly, for melanomas located within 2.5 cm of the Sappey line, drainage can occur to the ipsilateral groin, axilla, or both [
Uncommon SNs | Interval SNs |
---|---|
Epitrochlear | Chest wall |
Popliteal | Deep back |
Lower neck | Flank |
Triangular intermuscular space | Occipital areas |
Internal mammary | |
Paravertebral | |
Intraabdominal |
Lymphoscintigram of a patient with a primary melanoma of the forearm, with intense uptake of radioactive colloid in an epitrochlear node and uptake of the tracer in axillary region.
Lymphoscintigram of a patient with a primary melanoma in the left flank, demonstrating axillary nodal drainage, and an interval sentinel node at level of the chest wall.
The introduction of the sentinel node procedure with dynamic lymphoscintigraphy opened a new era in the management of lymph node staging in oncology. Functional study of the lymphatic pathway has changed the approach to nodal staging at diagnosis. In the last 15 years the Sappey’s rules, that governed lymphatic drainage in the last century, have been changed by dynamic lymphoscintigraphy to identify the node receiving direct lymphatic drainage from a primary tumor site. Out of classical lymph node basins, such as cervical, axillary, and groin, new “nonclassical” node sites appeared and have been reported widely in literature with different terms.
The incidence of uncommon/interval sentinel nodes varies widely in literature from 3.1% to 9.8%. This variability can be related to the different terms and definitions used to refer to an uncommon/interval node, to the different tracers used, and to the different modality of injection of the tracer.
The radiocolloids that best allow the identification of SNs are those that easily penetrate the lymphatic capillaries because of the particle sizes of 5–50 nm [
High quality lymphoscintigraphy requires specific high-resolution collimators for optimal gamma-camera imaging, with the use of detailed imaging protocols, in order to incorporate all anatomic areas to exclude uncommon/interval sentinel nodes sites. The accuracy may reflect a variable identification rate of unpredicted SNs [
Interval nodes were mostly associated with primary melanomas of the trunk. Uren among 3280 patients with cutaneous melanoma found 20% unexpected drainage from primary of the trunk. He described unexpected drainage from melanomas of the torso to the neck, to the TIS, to the subcutaneous fat over the costal margin, and also to the paravertebral, para-aortic, or retroperitoneal areas [
In most cases, drainage from truncal melanomas is associated to axillary or groin drainage. Recent studies have suggested that multiple lymphatic drainage in patients with truncal melanoma, compared with drainage to just one basin, is independently associated with an increased risk of lymph node metastases and with a worse prognosis even when no pathologic lymph node involvement was identified [
Uncommon sentinel nodes were frequently identified for cutaneous melanomas of the extremities. In melanomas of the upper limb, Uren described drainage in the epitrochlear region in 20% of patients, in the TIS in 6%, higher than our series probably due to the different radiotracer used [
de Wilt et al. demonstrated sentinel nodes in discordant fields in 31.5% of patients with head and neck melanomas, but they considered postauricolar nodes, occipital nodes, preauricular nodes, cheek nodes, axillary nodes, or sentinel nodes in the TIS, as unexpected basin demonstrating that such nodes can easily be overlooked without performing high, resolution and multiple, view lymphoscintigraphy [
McMasters et al. in a multicenter study and Tanabe, found the same frequency of tumor-positive sentinel nodes in unexpected and classical basin cases [
Sumner III et al. declared that completion lymph node dissection of both the unexpected site and the regional lymph node basin upstream from it is always mandatory [
The introduction of lymphoscintigraphy and sentinel lymph node biopsy has changed the approach to the staging of lymph node disease in oncology, permitting to identify micrometastatic nodal involvement. In rare cases dynamic lymphoscintigraphy shows sites of lymphatic drainage in nonclassical basins never described in the past when lymphatic drainage was considered only according to the anatomical proximity of the tumor primary site [
For the uncommon sentinel node sites, like popliteal or epitrochlear, an elective dissection may be adopted, to avoid a reoperation in case of a positive sentinel node. Both for uncommon and interval tumor-positive sentinel node, the extension of surgical dissection to the nearest classical basin remains controversial but may be avoided when there is no other parallel basin of drainage identified at lymphoscintigraphy. This may be true especially for interval sites that might be considered completely ripped from the nearest classical basin. For uncommon/interval intraabdominal or intrathoracic sentinel sites, the biopsy may be avoided in favor of careful followup with clinical imaging method.