Pathologist initiated reflex BRAF mutation testing in metastatic melanoma: experience at a specialist melanoma treatment centre.
Abstract Testing for BRAF mutations in metastatic melanoma is pivotal to identifying patients suitable for targeted therapy and influences treatment decisions regarding single agent versus combination immunotherapy. Knowledge of BRAF V600E immunohistochemistry (IHC) results can streamline decisions during initial oncology consultations, prior to DNA-based test results. In the absence of formal guidelines that require pathologist initiated ('reflex') BRAF mutation testing, our institution developed a local protocol to perform BRAF V600E IHC on specimens from all stage III/IV melanoma patients when the status is otherwise unknown. This study was designed to evaluate the application of this protocol in a tertiary [...]
Representativeness of the Index Lymph Node for Total Nodal Basin in Pathologic Response Assessment After Neoadjuvant Checkpoint Inhibitor Therapy in Patients With Stage III Melanoma
Abstract Importance: Neoadjuvant checkpoint inhibition in patients with high-risk stage III melanoma shows high pathologic response rates associated with a durable relapse-free survival. Whether a therapeutic lymph node dissection (TLND) can be safely omitted when a major pathologic response in the largest lymph node metastasis at baseline (index lymph node; ILN) is obtained is currently being investigated. A previous small pilot study (n = 12) showed that the response in the ILN may be representative of the pathologic response in the entire TLND specimen. Objective: To assess the concordance of response between the ILN and the total lymph node bed in [...]
The progressive relationship between increasing Breslow thickness and decreasing survival is lost in patients with ultrathick melanomas (≥15 mm in thickness)
Abstract Background: Survival tends to decrease as the Breslow thickness of a primary melanoma increases. However, little is known about the prognostic value of Breslow thickness in patients with very thick melanomas. Objective: We sought to assess survival in patients with melanomas ≥4.0 mm in Breslow thickness. Methods: A pooled cohort of 5595 patients (4107 Dutch and 1488 Australian) with melanomas ≥4.0 mm in thickness diagnosed from 2000 to 2014 was analyzed. Standard and spline Cox regressions were generated for overall survival (OS) and recurrence-free survival (RFS). Results: The median follow-up was 3.4 years. The continuous hazard ratios (HRs) for OS and RFS [...]
The progressive relationship between increasing Breslow thickness and decreasing survival is lost in patients with ultrathick melanomas (≥15 mm in thickness).
Abstract Background: Survival tends to decrease as the Breslow thickness of a primary melanoma increases. However, little is known about the prognostic value of Breslow thickness in patients with very thick melanomas. Objective: We sought to assess survival in patients with melanomas ≥4.0 mm in Breslow thickness. Methods: A pooled cohort of 5595 patients (4107 Dutch and 1488 Australian) with melanomas ≥4.0 mm in thickness diagnosed from 2000 to 2014 was analyzed. Standard and spline Cox regressions were generated for overall survival (OS) and recurrence-free survival (RFS). Results: The median follow-up was 3.4 years. The continuous hazard ratios (HRs) for OS and RFS [...]
BRAF mutation testing for patients diagnosed with stage III or stage IV melanoma: practical guidance for the Australian setting
Abstract Targeted therapy (BRAF inhibitor plus MEK inhibitor) is now among the possible treatment options for patients with BRAF mutation-positive stage III or stage IV melanoma. This makes prompt BRAF mutation testing an important step in the management of patients diagnosed with stage III or IV melanoma; one that can help better ensure that the optimal choice of systemic treatment is initiated with minimal delay. This article offers guidance about when and how BRAF mutation testing should be conducted when patients are diagnosed with melanoma in Australia. Notably, it recommends that pathologists reflexively order BRAF mutation testing whenever a [...]
Road to Metastasis: The TWEAK Pathway as a Discriminant between Metastasizing and Non-Metastasizing Thick Melanomas
Abstract Cutaneous melanoma (CM) is the most aggressive form of skin cancer, and its worldwide incidence is rapidly increasing. Early stages can be successfully treated by surgery, but once metastasis has occurred, the prognosis is poor. However, some 5-10% of thick (≥2 mm) melanomas do not follow this scenario and run an unpredictable course. Little is known about the factors that contribute to metastasis in some patient with thick melanomas and the lack thereof in thick melanoma patients who never develop metastatic disease. We were therefore interested to study differential gene expression and pathway analysis and compare non-metastatic and [...]
Melanoma with osseous or chondroid differentiation: a report of eight cases including SATB2 expression and mutation analysis.
Abstract Melanoma can present with osteocartilaginous differentiation, however few reports exist on this rare subtype. We present eight cases of melanoma with osteocartilaginous differentiation to highlight its clinical, pathological and molecular features. The cases showed no association with gender (5 males and 3 females) or age (range 23-84 years). Cases included both primary melanomas and distant metastases (6 and 2, respectively), with the majority arising from cutaneous sites (7/8) and the remaining case from a mucosal site. Tumour-infiltrating lymphocyte (TIL) score ranged from 0 to 3 (median 1), and 2/8 lesions had evidence of inflammatory changes or antecedent trauma. [...]
Lentigo maligna: defining margins and predictors of recurrence utilising clinical, dermoscopic, confocal microscopy and histopathology features
Abstract Background: Lentigo maligna (LM) is a subtype of melanoma in situ with poorly defined margins and a high recurrence rate. The biological behaviour of LM appears to differ widely between cases, from biologically indolent to biologically active variants, with some patients experiencing multiple recurrences. It is not known whether this is secondary to inadequate margins, field cancerization or the innate biology of the lesion itself. Objectives: (a) Describe the margins of LM in detail by analysing LM in three zones, that is centre, edge and surround using reflectance confocal microscopy (RCM) and histopathology; (b) ascertain association of histological distance of [...]
Not all melanomas are created equal: A review and call for more research into nodular melanoma
Abstract Among the histogenic subtypes of melanoma, nodular melanoma (NM) is the major contributor for thicker and fatal melanomas and it has been associated with melanoma-specific death in thin tumours, highlighting an important subgroup of 'aggressive thin' melanomas. This review provides a synthesis of the distinct characteristics of NM, with respect to epidemiology and risk factors, clinical presentation, histopathology, molecular and dermoscopic aspects, and screening practices. The real challenges are to find better biomarkers of aggressiveness and to know whether the control of such aggressive melanomas can be influenced by targeted interventions such as early detection, drug interventions and [...]