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Melanoma Diagnosis and Work-up of Malignant Melanoma in the Age of Fine Needle Aspiration and Molecular Testing Lester J Layfield, MD Professor and Chair, Department of Pathology & Anatomical Sciences, University of Missouri, Columbia, US Abstract Melanoma is one of the most aggressive skin cancers and is prone to both local recurrence and distant metastases. Primary treatment usually includes wide excision and sentinel lymph node biopsy. Clinical and pathologic staging is important for estimating the potential for metastasis and influences post-resection follow-up protocols. Because stage I and II melanomas metastasize infrequently, asymptomatic patients with these low-stage malignancies do not require routine imaging studies. Patients with positive sentinel lymph nodes often undergo routine examination (for staging) using computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET) despite evidence showing a very low yield for such testing. Patients with stage III disease and local recurrence should undergo further testing including serum lactate dehydrogenase (LDH), chest radiograph, CT, and PET due to increased risk for systemic metastases. Imaging abnormalities may undergo fine needle aspiration, core biopsy, or open biopsy for confirmation of diagnosis and to obtain tissue for ancillary studies. Depending on the availability of treatment protocols ancillary testing may include mutational analysis for BRAF V600-E, CKIT, and NRAS. Keywords Melanoma, metastases, biopsy, imaging, FNA Disclosure: The author has no conflicts of interests to declare. Received: December 23, 2013 Accepted: March 12, 2014 Citation: Oncology & Hematology Review, 2014;10(1):21–4 Correspondence: Lester J Layfield, MD, Professor and Chair, Department of Pathology & Anatomical Sciences, University of Missouri, One Hospital Drive, M263 Medical Sciences Building, Columbia, MO 65212, US. E: Malignant melanoma is an aggressive form of skin cancer and has demonstrated an increasing mortality among men in the last quarter century. 1 The 5-year survival rate is approximately 15–20  % for stage IV melanoma. 2 Surgical management of primary melanoma remains wide excision with or without the addition of sentinel lymph node biopsy. While 5-year survival for stage I and II melanomas is good, outcome for stage IV melanoma remains bleak. Recently, a number of directed therapies have been developed for treatment of metastatic malignant melanoma. Many of these are predicated on the presence of specific mutations sensitizing the malignant cells to specific chemotherapeutic agents. Molecular techniques are required to document the specific mutations, thus tissue from metastatic sites is needed to guide selection of specific therapies. Given that specific therapies with efficacy against metastatic disease now exist, the early recognition of distant metastases by imaging modalities and their biopsy have become important in the management of stage III and IV melanoma patients. Herein, we review blood marker testing, imaging methods and indications, biopsy techniques, and ancillary testing for directed therapies in patients with metastatic malignant melanoma. The current review is limited to cutaneous melanoma and its metastases. the presence of any family history of melanoma or other skin cancer as well as whether or not there is a family history of multiple, irregular, or prominent moles. The history should also include documentation of the presence or absence of pancreatic ductal carcinoma or astrocytoma within the family. The patient should be specifically questioned about a history of prior personal melanomas. A history of significant prior sun exposure should be documented. The patient should be asked about changes they have noted in other moles specifically regarding alterations in size, color, shape, or the presence of bleeding or ulceration. A personal history or family history of multiple nevus syndrome should be queried. Clinical History and Initial Physical Examination The index atypical pigmented lesion should be excised in total if possible. Shave biopsies are suboptimal specimens as they may preclude accurate evaluation of depth of invasion and assessment of architectural features Following the identification of a clinically suspicious pigmented lesion, the patient should have a focused medical history taken documenting © To u ch MEd ica l MEdia 201 4 Physical examination should include a total body skin examination with photography of nevi and other suspicious cutaneous lesions. This total body skin examination is performed to assess the number of nevi present and to distinguish between typical and atypical lesions. Biopsy of Primary Lesion and Histologic Examination 21