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Diagnosis and Work-up of Malignant Melanoma in the
Age of Fine Needle Aspiration and Molecular Testing
Lester J Layfield
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 pathological 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 of 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: Lester J Layfield has no conflicts of interests to declare. No funding was received in the publication of this article.
Received: 23 December 2013 Accepted: 12 March 2014 Citation: European Oncology & Haematology, 2014;10(1):58–61
Correspondence: Lester J Layfield, Professor and Chair, Department of Pathology & Anatomical Sciences, University of Missouri, One Hospital Drive, M263 Medical
Sciences Building, Columbia, MO 65212, US. E: email@example.com
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 sensitising 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. In this article, blood
marker testing, imaging methods and indications, biopsy techniques
and ancillary testing for directed therapies in patients with metastatic
malignant melanoma are reviewed. The current article is limited to
cutaneous melanoma and its metastases.
Clinical History and Initial Physical
Examination Following the identification of a clinically suspicious pigmented
lesion, the patient should have a focused medical history taken
58 documenting 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, colour, shape or the
presence of bleeding or ulceration. A personal history or family
history of multiple nevus syndrome should be queried.
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
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 that are important for diagnosis. Excisional
biopsies are recommended because they allow the evaluation of
junctional activity at the edges of the lesion and the deep margin. Such
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