Melanoma of unknown primary: Experience at Massachusetts General Hospital and Dana-Farber Cancer Institute
University of Texas MD Anderson Cancer Center, Houston, Texas, United States Melanoma Research
(Impact Factor: 2.28).
02/2005; 15(1):77-82. DOI: 10.1097/00008390-200502000-00013
Melanoma may present metastatically without an identifiable primary lesion. To further characterize the epidemiology of melanoma of unknown primary (MUP), we report our experience with a cohort of MUP patients. We retrospectively reviewed patients seen at the Massachusetts General Hospital (MGH) and the Dana-Farber Cancer Institute (DFCI) between 1986 and 1996 with follow-up to 2002. Data were analysed using log-rank and proportional hazards analyses, with death from any cause as the main outcome measure. Of the 2485 melanoma patients seen, 65 (2.6%) had MUP; 41 patients were male [63.1%; 95% confidence interval (CI), 50.2%, 74.7%]. The median age at diagnosis was 54.1 years (interquartile range, 39.4-67.1 years). Thirty patients had lymph node metastases, 12 cutaneous or subcutaneous metastases and 23 visceral metastases. Of the 62 patients (95.4%) with at least some follow-up, there were 42 deaths from any cause. Patients with lymph node metastases survived significantly longer than patients with other metastases [5-year survival 38.7% (95% CI, 18.1%, 59.1%) vs. 13.9% (95% CI, 4.4%, 28.6%); P<0.01]. After adjusting for stage and age at diagnosis, there was some evidence that men survived longer than women [hazard ratio (HR)=0.55; 95% CI, 0.28, 1.09]. Survival did not differ amongst patients with different types of non-lymph node metastases. The 5-year survival rates in this cohort did not differ from those of historical controls with known primaries. The demographic and survival characteristics of this MUP cohort mirrored those found in previous studies. More studies of MUP patients, as well as a standardized definition of MUP, may shed light on the pathogenesis and prognosis of MUP.
Available from: Lucie Heinzerling
- "While in the literature V600E2, V600D, V600G, V600R, and L597S (Beadling et al, 2011; Dahlman et al, 2012) have been described this is the first study to report more complex mutations such as V600EK601del and V600DK601del in melanoma. Remarkably, 21% of patients with rare mutations analysed in our study presented with melanoma of unknown primary (MUP), which is much higher than the 1–8% in previously documented cases (Katz et al, 2005; Cormier et al, 2006). "
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The detection of V600E BRAF mutation in melanoma is fundamental since here BRAF inhibitors represent an effective treatment. Non-V600E BRAF mutations that may also respond are not detected by certain screening methods. Thus, knowledge about detection of these mutations is needed.
A total of 276 tumour samples from 174 melanoma patients were investigated for BRAF mutations by pyrosequencing. Rare mutations were confirmed by capillary sequencing and compared with findings from COBAS test and immunohistochemistry using a novel BRAF antibody. Melanoma type, localisation, and survival were summarised.
BRAF mutations were found in 43% of patients (124 tumours in 75 patients). Among those, 14 patients (18.7%) exhibited rare mutations. The V600EK601del and V600DK601del mutations have never been described before in melanoma. Furthermore, V600K, V600E2, and V600D, V600G, V600R, and L597S mutations were detected. Mutations were not detected by COBAS test in 7 out of these 14 patients and immunohistochemistry only reliably detected patients with the V600E2 and V600EK601del mutation.
Accurate diagnosis of rare BRAF mutations is crucial. We show that pyrosequencing is accurate, highly sensitive, reliable, and time saving to detect rare BRAF mutations. Missing these rare variant mutations would exclude a subset of patients from available effective BRAF-targeting therapy.
Available from: ncbi.nlm.nih.gov
- "According to the published literature, approximately 5-10% of patients with metastatic melanoma have a primary melanoma of unknown origin [13,14]. Various reasons, such as occult cutaneous or visceral location, complete regression, or primary origin in lymph nodes due to malignant transformation of ectopic nevus cells, have been suggested [15,16]. Multiple nodules of the lung are generally considered intrapulmonary metastases. "
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ABSTRACT: Malignant melanoma involving the respiratory tract is nearly always metastatic in origin, and primary tumors are very rare. To our knowledge, about 30 cases have been reported in the English literature, one of which involved multiple brain metastases. Here, we report two cases of primary pulmonary malignant melanoma. The first case, which occurred in a 52-year-old Chinese female patient who died 4 months after the initial diagnosis, involved rapid intrapulmonary and intracranial metastases. The second patient, a 65-year-old female, underwent surgical excision, and clinical examination, histopathological characteristics, and immunohistochemical features supported the diagnosis of pulmonary malignant melanoma. No evidence for recurrence and/or metastasis has been found more than one year after the initial surgery. To establish the diagnosis of primary pulmonary malignant melanoma, any extrapulmonary origin must be excluded by detailed examination. Moreover, the tumor should be removed surgically whether it occurs as a single lesion or multiple lesions.
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1480477335765055.
Available from: Alexander Christopher Jonathan van Akkooi
- "In 8% to 20% of all therapeutic lymph node dissections (TLND) for regional metastatic melanoma, no primary tumor can be found.4,5 Possible explanations for the absence of a primary tumor are spontaneous regression, unidentified primary melanoma, previous excision of what was considered a benign lesion or a malignant transformation of an ectopic nodal melanocyte.4,6 Whether patients with MUP have better or worse prognosis than patients with melanoma of known primary site (MKP) presented with nodal metastases is uncertain. "
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ABSTRACT: The aim of this study was to evaluate the incidence and outcome of melanoma of unknown primary site (MUP) after therapeutic lymph node dissection (TLND) of palpable nodal melanoma metastases. Disease-free (DFS) and overall survival (OS) time of MUP patients were analyzed and compared to patients undergoing a TLND for known primary melanomas (MKP).
This single institution retrospective study analyzed 342 consecutive patients who were treated with 415 TLNDs for palpable nodal disease from 1982 to 2009. Univariate and multivariate analyses included: MUP versus MKP, gender, Breslow thickness, ulceration of primary tumor, site of primary tumor, site of dissection, extracapsular extension, number of collected nodes, number of positive nodes and the node positive ratio.
A total of 47 MUP were identified in 342 patients (13.7%). In univariate analysis, a trend was seen toward better survival for MUP patients compared to MKP patients having 5-year OS rates of 40% and 27%, respectively (P = 0.06). Multivariate analysis for OS showed two highly significant factors associated with worse prognosis: extracapsular extension and N3 status (both P < 0.001). Two factors were associated with a significant better prognosis: MUP (P = 0.03) and a neck dissection (P = 0.04).
Patients with MUP showed a statistically significant better OS compared to patients with melanoma metastases from known primary tumors. Presence of extracapsular extension and an increased number of positive nodes are statistically significantly negative prognostic factors for OS. The absence of a primary melanoma in stage III melanoma patients does not preclude surgery.
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