The critical role of pathology in the multidisciplinary care of melanoma patients is becoming apparent in the rapidly changing modern era of personalised and precisely targeted medicine. Recent insights into the molecular pathogenesis of melanoma have allowed traditional pathological assessment to be supplemented and enhanced by molecular pathology testing to improve classification, prognostication and selection of patients for targeted therapies. The pathology report remains pivotal as it establishes the definitive diagnosis of melanoma in most instances, while the assessment and documentation of key pathological parameters allow the most accurate determination of prognosis to be made and are utilised to guide the next stages of patient management. Molecular tests (including fluorescent in situ hybridisation) are now routinely utilised to enhance the accuracy of classification and prognostication of selected melanocytic tumours in many institutions. Recent studies have also highlighted important melanoma prognosticators such as mitotic rate, the presence and extent of ulceration, tumour-infiltrating lymphocyte grade and sentinel lymph node biopsy. Pathologists also play a key role in the triage and selection of appropriate tumour tissue and tumour cells to test for various molecular markers which are used to select patients who may benefit from targeted therapies. It is important that clinicians understand important aspects of molecular testing in melanoma, such as when and how to arrange testing, which specimen to test, and the advantages and disadvantages of the various testing methodologies. These issues are addressed in this review. Pathology is a key component of the multidisciplinary care of melanoma patients. While melanoma may be suspected clinically, the initial definitive diagnosis is usually established by pathological examination of a tissue biopsy. In clinically localised primary cutaneous melanoma, pathological assessment of various tumour parameters enables accurate estimation of prognosis and determines the most appropriate next step(s) in clinical management. Pathological evaluation of any potential or likely metastasis is also critical. Recent discoveries of the molecular pathogenesis of melanoma are now being harnessed clinically to improve patient management. Molecular pathology is now utilised to enhance melanoma diagnosis, classification, prognostication and to predict responsiveness to selective targeted therapies in melanoma, and will undoubtedly play an ever-increasing role in the management of melanoma patients. In this article we review selected important issues in melanocytic
A 38-year-old Indonesian man presented with a single anaesthetic plaque on his right forearm and no other sensory changes. His clinical presentation was consistent with tuberculoid leprosy, but histopathology of a skin biopsy from the lesion showed borderline lepromatous disease. The patient was treated with multidrug therapy for multibacillary disease. Seven months after initiation of treatment his solitary skin anaesthetic plaque became tumid, and he developed multiple small plaques on his arms, legs and face, without evident neuritis. He was clearly in a reversal reaction (type 1), which slowly resolved with treatment of prednisone.
Read moreAlthough vascular neoplasms of the spleen are rare, they are the most common nonhemopoietic proliferation of the organ, and include hemangiomas, lymphangiomas, hamartomas, littoral cell angiomas, hemangioendotheliomas, and angiosarcomas, as well as the recently described myoid angioendothelioma (MA). MA is an uncommon, benign tumor of the spleen, which is morphologically characterized by a composite of vascular spaces and stromal cells with myoid features. In 1999, in the only report of this unusual neoplasm, Kraus and Dehner described the features of 3 cases. We present another case of MA of the spleen occurring in a 51-year-old man that demonstrated the characteristic morphologic and immunohistochemical features of this neoplasm. In addition to the features described by Kraus and Dehner, our case also displayed the previously unreported findings of focal spindling of the stromal cells and scattered S100-positive cells in the stroma. The case was further unique in having a central stellate scar. Careful attention to histology, possibly with the aid of immunohistochemistry, should distinguish other splenic neoplasms from MA. Although MA is a morphologically distinct lesion, its histologic spectrum, biological behavior, and relationship to other vascular tumors are yet to be fully discovered. It is hoped that the recognition of further cases, and the use of newer molecular technologies, will help better define the nosological position and implications of the diagnosis of this unusual tumor.
Read moreSuccess with molecular-based targeted drugs in the treatment of cancer has ignited extensive research efforts within the field of personalized therapeutics. However, successful application of such therapies is dependent on the presence or absence of mutations within the patient's tumor that can confer clinical efficacy or drug resistance. Building on these findings, we developed a high-throughput mutation panel for the identification of frequently occurring and clinically relevant mutations in melanoma. An extensive literature search and interrogation of the Catalogue of Somatic Mutations in Cancer database identified more than 1,000 melanoma mutations. Applying a filtering strategy to focus on mutations amenable to the development of targeted drugs, we initially screened 120 known mutations in 271 samples using the Sequenom MassARRAY system. A total of 252 mutations were detected in 17 genes, the highest frequency occurred in BRAF (n = 154, 57%), NRAS (n = 55, 20%), CDK4 (n = 8, 3%), PTK2B (n = 7, 2.5%), and ERBB4 (n = 5, 2%). Based on this initial discovery screen, a total of 46 assays interrogating 39 mutations in 20 genes were designed to develop a melanoma-specific panel. These assays were distributed in multiplexes over 8 wells using strict assay design parameters optimized for sensitive mutation detection. The final melanoma-specific mutation panel is a cost effective, sensitive, high-throughput approach for identifying mutations of clinical relevance to molecular-based therapeutics for the treatment of melanoma. When used in a clinical research setting, the panel may rapidly and accurately identify potentially effective treatment strategies using novel or existing molecularly targeted drugs.
Read moreThe authors wish to apologise for writing the name of the final author of this paper incorrectly. The correct way to write his name is C. Soon Lee.
Read moreZhuang, L.1; Lee, C.1; Scolyer, R.1 2; McCarthy, S.1 2; Zhang, X.3; Thompson, J.2; Hersey, P.2 3 Author Information
Read moreIf melanoma is suspected, initial excision biopsy is recommended. Wide excision margins are then based on reported tumour thickness. Sentinel lymph node biopsy provides important prognostic information and a probable survival benefit for patients with intermediate thickness melanomas. Other staging tests are not indicated in patients with clinically localised primary melanomas. Complete lymph node dissection is required if microscopic or macroscopic disease is present in regional nodes. Intransit metastases are best managed at specialist melanoma treatment centres. For patients with widespread systemic metastases, new drug treatments including BRAF inhibitors and anti-CTLA4 antibodies are prolonging survival, but unfortunately most patients ultimately relapse.
Read moreIn vivo RCM can provide valuable information facilitating optimal patient care management.
Read morePathological assessment of a tissue biopsy is a critical aspect in the multidisciplinary management of melanoma patients because it not only establishes a definite diagnosis in most cases but also provides information that to a major extent influences patient prognosis and directs initial further management. For the pathological report to be as accurate as possible, it is important that the clinician provides the pathologist with an adequate tissue sample and appropriate clinical details. If circumstances permit, an excision biopsy with narrow clearance margins is the most appropriate biopsy of a melanocytic tumour. This will enable an accurate assessment and allow definitive treatment to be planned appropriately if a diagnosis of melanoma is confirmed. Incomplete biopsies (such as shave, punch or curetting biopsies) may impair the accuracy of pathological diagnosis and the assessment of some important parameters and should be avoided if possible. Clinical factors that influence pathological assessment of melanocytic tumours include patient age and sex, the site of the lesion and others factors (such as prior biopsy, other trauma, surface irritation, pregnancy, topical treatment and recent strong sunlight exposure) should be communicated to the pathologist. The latter features may induce atypical pathological features and lead to a misdiagnosis of melanoma. The prognosis for patients with localised primary cutaneous melanoma depends principally on tumour thickness, but other factors such as the presence or absence of ulceration, mitotic rate, Clark level, anatomical site, age and sex are also important. The distance of the tumour from the excision margins and the presence of desmoplasia, neurotropism, regression, satellites or vessel involvement are other features that may affect prognosis and management. It is therefore important that the pathology report details all these factors. The use of a synoptic format pathology report can facilitate this. (author abstract)
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