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Cooper C.L.,Royal Prince Alfred Hospital | Murali R.,Royal Prince Alfred Hospital | Murali R.,Melanoma Institute | Murali R.,University of Sydney | And 9 more authors.
Melanoma Research | Year: 2010

Fine-needle biopsy (FNB) is commonly used in the investigation of patients with a history of melanoma who present with possible metastatic disease. Non-melanoma malignancies (NMM) are common in the general population and not infrequent in patients with melanoma. Such tumors may be difficult to distinguish from metastatic melanoma on FNB. We sought to determine the types of NMMs that occur in melanoma patients, to document the frequency with which they were diagnosed by FNB, and to highlight potential pitfalls in cytologic diagnosis. NMMs occurring in 1416 consecutive melanoma patients who underwent FNB of 2204 clinically suspicious lesions between 1992 and 2002 at a single center were reviewed and analyzed. The sites of FNB included lymph nodes (36.9%), skin and subcutis (25.1%), visceral locations (17.9%), and other sites (20.0%). Of the 1416 melanoma patients investigated by FNB, 116 (8.2%) had a metachronous or synchronous NMM; the NMM was diagnosed by the FNB in 17 (14.7%) patients. The most common NMMs were epithelial tumors (69.4%, most commonly carcinomas of large bowel, breast and prostate) and hematologic malignancies (21.8%). As NMMs are not infrequent in patients with melanoma, they should always be considered in the differential diagnosis of clinically suspicious masses in patients with a history of melanoma, as well as in patients at high risk of melanoma. Careful assessment of the FNB cytologic features and directed use of ancillary studies should enable accurate diagnosis in most cases and facilitate appropriate patient management. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Rizos H.,University of Sydney | Menzies A.M.,Melanoma Institute | Pupo G.M.,University of Sydney | Carlino M.S.,University of Sydney | And 26 more authors.
Clinical Cancer Research | Year: 2014

Purpose: Multiple BRAF inhibitor resistance mechanisms have been described, however, their relative frequency, clinical correlates, and effect on subsequent therapy have not been assessed in patients with metastatic melanoma. Experimental Design: Fifty-nine BRAFV600-mutant melanoma metastases from patients treated with dabrafenib or vemurafenib were analyzed. The genetic profile of resistance mechanisms and tumor signaling pathway activity was correlated with clinicopathologic features and therapeutic outcomes. Results: Resistance mechanisms were identified in 58% progressing tumors and BRAF alterations were common. Gene expression analysis revealed that mitogen-activated protein kinase (MAPK) activity remained inhibited in 21% of resistant tumors, and the outcomes of patients with these tumors were poor. Resistance mechanisms also occurred in pretreatment biopsies and heterogeneity of resistance mechanisms occurred within patients and within tumors. There were no responses to subsequent targeted therapy, even when a progressing tumor had a resistance mechanism predicted to be responsive. Conclusions: Selecting sequential drugs based on the molecular characteristics of a single progressing biopsy is unlikely to provide improved responses, and first-line therapies targeting multiple pathways will be required. ©2014 AACR.

Melstrom L.G.,Sloan Kettering Cancer Center | Taylor E.,Melanoma Institute | Taylor E.,University of Sydney | Kuk D.,Sloan Kettering Cancer Center | And 10 more authors.
Annals of Surgical Oncology | Year: 2014

Background: Melanoma patients with palpable nodal disease in more than one basin have a worse prognosis than those with single-basin disease. Little is known about the outcome of patients with microscopically positive nodal disease in more than one basin, or how they are currently managed at tertiary referral centers.Methods: We identified 97 patients with positive sentinel lymph nodes (SLNs) in more than one lymph node basin from 1994 to 2010 from three tertiary care centers. Clinical and pathologic outcome variables were analyzed.Results: Ninety-seven patients (72 men, 25 women) were identified with at least one positive SLN in at least two node basins. Most primary tumors were truncal (68, 70 %) followed by extremity (16, 17 %) and head/neck (13, 13 %). The median Breslow depth was 3.2 mm (range 0.8–12 mm), and 49 (51 %) were ulcerated. The most frequently involved nodal basins were the axilla (112, 57 %), neck (40, 20 %), and groin (24, 12 %). Seventy-seven percent (153 of 198) of all positive SLN basins underwent completion lymph node dissection (CLND). Most patients (54, 56 %) developed recurrent disease, with a median time to recurrence of 20 months. The majority of first recurrences were distant (42, 43 %), followed by regional nonnodal metastases (17, 18 %) and regional nodal metastases (16, 16 %). There was no significant difference in median overall survival between CLND versus no-CLND groups (45 vs. 30 months, respectively).Conclusions: Most melanoma patients with more than one SLN-positive basin are currently managed with CLND. Outcomes after CLND and no CLND are similarly poor; therefore, consideration of close nodal observation may be more appropriate. © 2014, Society of Surgical Oncology.

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