Individualized Surgery: Gamma-Probe-Guided Lymphadenectomy in Patients with Clinically Enlarged Lymph Node Metastases from Melanomas

Lutz Kretschmer 2 Carsten-Oliver Sahlmann 1 Pavel Bardzik 1 Christina Mitteldorf 0 Hans-Joachim Helms 3 Johannes Meller 1 Michael Peter Schon 2 Hans Peter Bertsch 2 L. Kretschmer e-mail: 0 Department of Dermatology , Venereology and Allergology, Klinikum Hildesheim GmbH, Hildesheim, Germany 1 Department of Nuclear Medicine, Georg-August-University of Gottingen , Gottingen, Germany 2 Department of Dermatology , Venereology and Allergology, Georg August University , Gottingen, Germany 3 Department of Medical Statistics, Georg August University of Gottingen , Gottingen, Germany Background. The value of a preoperative lymphoscintigraphy in melanoma patients with clinically evident regional lymph node metastases has not been studied. Therapeutic lymph node dissection (TLND) is regarded as the clinical standard, but the appropriate extent of TLND is controversial in all lymphatic basins. Patients and Methods. Of the 115 consecutive patients with surgery on palpable lymph node metastases, 34 received a pre-operative lymphoscintigraphy. Lymphatic drainage to a second nodal basin outside the clinically involved basin was found in 15 cases. In 13 patients, the ectopic tumor-draining lymph nodes were excised as in a sentinel node biopsy. The lymph nodes from the TLND specimens were postoperatively separated and classified as either radioactive or non-radioactive. Results. A total of 493 lymph nodes were examined pathologically. The largest macrometastasis maintained the ability to take up radiotracer in 77% of cases. Radioactively labeled lymph nodes carried a higher risk of being involved with metastasis. The proportions of tumor involvement for radioactive and non-radioactive lymph nodes were 44.5 and 16.9%, respectively (P=0.00002). Of the 13 ectopic nodal basins surgically explored, six harbored clinically occult metastases. - Lymph node metastasis is the most frequent form of first recurrence in patients with cutaneous melanoma if no lymph node surgery was performed at initial diagnosis.1 Regional metastases of melanomas most frequently involve the cervical, axillary or inguinal lymph node basins. Lymphatic mapping with sentinel lymphadenectomy (SLNB) has become the standard approach in treating highrisk melanoma patients with clinically unsuspicious regional lymph nodes. SLNB studies have shown that lymphatic drainage to a second or even third nodal basin is not uncommon; this happens most frequently in patients with melanomas originating on the trunk.24 Although melanomas located on extremities usually drain to the ipsilateral inguinal or axillary basins, additional drainage to interval nodes, iliac, popliteal or epitrochlear SLNs may be found.57 Since occult lymphatic metastases most often occur in the primary tumor-draining lymph nodes, there is consensus that sentinel lymph nodes (SLNs) should be excised regardless of their anatomic location. In patients with palpably enlarged node metastases, the current standard procedure is therapeutic regional lymph node dissection (TLND) of the involved nodal basin. The value of lymphatic mapping has not yet been studied. The experience with SLNB suggests, however, that clinically occult metastasis to a second nodal basin might represent a realistic danger also for patients with enlarged nodes, especially when the primary melanoma site is suggestive for ambiguous lymphatic drainage. Moreover, as with SLNB, the clinically unsuspicious but radioactively labeled lymph nodes within a nodal basin might carry a higher risk of metastasis, even after the formation of macrometastases. If so, the anatomic location of the radioactive nodes within a nodal basin might influence the extent of the lymph node dissection. The high morbidity and significant nodal basin recurrence rates following TLND make it necessary to pursue two aims in testing lymphatic mapping in patients with enlarged node metastases: (1) to detect all lymph nodes at risk for metastasis and (2) to avoid unnecessary extension of the node dissection. In the present analysis, we focus on these questions by reviewing 34 patients treated individually who received lymphoscintigraphy prior to excision of clinically enlarged regional lymph node metastases. PATIENTS AND METHODS Between May 1998 and May 2011, 115 consecutive patients with clinically evident regional lymph node metastases from melanomas were treated at the University Medical Center in Gottingen. Of these, 25 had developed nodal recurrence following negative SLNB. There was no history of primary melanoma and no primary tumor could be located in 14 additional patients. The remaining 76 patients, who are the subject of the present study, had a known primary melanoma but no previous lymphoscintigraphy. In 29 patients, the primary melanoma was diagnosed at the same time as palpable metastases. Nodal recurrences after primary tumor excision were noted in 47 patients. Magnetic resonance imaging of the head and neck were undertaken in patients with cervical metastases. All patients with inguinal nodal metastases received computed tomography scans in order to detect enlarged nodes in the lesser pelvis. The size of the lymphadenopathy was determined by preoperative ultrasound B-scans. In the majority of cases, fine-needle aspiration cytology was performed. In three patients who had undergone diagnostic metastasectomy, the size of the macrometastases was taken from the pathology report. Patients with clinical evidence of systemic metastases were not considered in the present study. Lymphatic Mapping From November 2000, 34 selected patients received preoperative lymphoscintigraphy. In this group, two patients were actually referred for SLNB but macrometastasis [1 cm was diagnosed on preoperative ultrasound B-scans. The remaining 32 patients had clinically palpable disease. Lymphatic mapping was deemed necessary: (1) if ambiguous lymphatic drainage from the primary melanoma site was conceivable or (2) if some kind of less radical lymph node dissection had been planned. In such cases, we aimed to excise all clinically unsuspicious but radioactive lymph nodes, even if they were situated beyond the borders of the previously designated node dissection field. All patients gave informed consent before undergoing gammaprobe-guided lymphadenectomy. Patients with unknown primary melanoma sites as well as the false-negative cases after initially negative SLNB did not receive lymphatic mapping. Lymphatic mapping was also not carried out for patients with clinically evident metastases in two nodal basins, for patients with enlarged pelvic metastases, or for patients with grossly enlarged, fixed or matted nodes. Patients who had a primary tumor excision requiring reconstruction of the defect using skin flaps did not undergo lymphoscintigraphy. Patients with previously excised in-transit metastases were also not considered eligible for lymphatic mapping. We did include, however, patients with synchronous, surgically amenable in-tran (...truncated)