The prognostic significance of microsatellites in cutaneous melanoma.

Microscopic satellite metastases are an adverse prognostic feature in primary cutaneous melanoma patients. The prognostic significance of microsatellites, including their number, size and distance from the primary melanoma, using the 8th edition American Joint Committee on Cancer definition, has not previously been evaluated. This study sought to determine the prognostic significance of microsatellites in histopathologically reviewed cases. Eighty-seven cases of primary cutaneous melanoma with the presence of microsatellites documented in the original pathology report and all histopathology slides available were reviewed and the findings were correlated with clinical outcome. Matched control cases were selected for all confirmed microsatellites cases. The presence of microsatellites was confirmed in 69 cases. The microsatellite group had significantly worse prognosis, with 21% 5-year disease-free survival compared with 56% in the control group (p < 0.001). The 5-year melanoma-specific survival was 53% in the microsatellites group and 73% in the control group (p = 0.004). Increasing distance (mm) of the microsatellite from the primary melanoma was found to adversely influence disease-free survival (HR = 1.24, 95% CI: 1.13-1.36, p < 0.001), overall survival (HR = 1.26 95%CI: 1.13-1.40, p < 0.001), and melanoma-specific survival (HR = 1.27 95% CI: 1.11-1.45, p < 0.001). Number and size of microsatellites were not significant prognostic factors. The presence of microsatellites was the only factor that proved to be an independent predictor of sentinel node positivity in multivariate analysis (OR 4.64; 95% CI 1.66-12.95; p = 0.003). Microsatellites were significantly associated with more loco-regional recurrences (p < 0.001) but not distant metastases (p = 0.821). Melanomas with microsatellites as defined by the 8th edition American Joint Committee on Cancer staging system are thus aggressive tumors, associated with significantly worse disease-free survival, overall survival and melanoma-specific survival. The presence of microsatellites is also associated with sentinel node-positivity and local and in-transit recurrence. Increasing distance of the microsatellite from the primary tumor is an independent adverse prognostic factor that warrants further evaluation.

Factors influencing the use of sentinel lymph node biopsy in the Netherlands.

BACKGROUND: In the US, whether a sentinel lymph node biopsy (SLNB) is performed depends on tumor and patient factors, including socioeconomic status (SES) and type of health care insurance. We analyzed which patient and tumor characteristics influenced the use of SLNB in a country where every patient has equal access to healthcare. METHODS: Patients diagnosed with a cutaneous invasive melanoma of ≥1 mm between 2004 and 2011 and living in the northeastern part of the Netherlands were selected from the Netherlands Cancer Registry. Regression analysis was performed to assess the association of patient and tumor characteristics and SLNB use. RESULTS: SLNB was performed in 42 % of the 2,413 included patients. The frequency of performing SLNB increased between 2004 and 2011 from 24 to 55 % (p < 0.001). Patients were less likely to undergo SLNB if they had a melanoma located in the head and neck area (p < 0.001), when they were over 55 years (p = 0.001), and if they had a low SES (p = 0.03). SLNB use was more likely when the diagnosis of melanoma was made in the university hospital (p = 0.045) or when the Breslow thickness was 2.01-4.0 mm (p = 0.03). CONCLUSIONS: The use of SLNB has increased significantly between 2004 and 2011. However, in 2011 it was still performed in only 55 % of the Dutch patients with a melanoma ≥1 mm. In patients with head and neck melanoma, older patients, and patients with low SES, SLNB was less frequently performed. Patients with T3 melanomas and a diagnosis made in the university hospital more often had an SLNB performed.

Pathology review significantly affects diagnosis and treatment of melanoma patients: an analysis of 5011 patients treated at a melanoma treatment center.

BACKGROUND: Pathologists sometimes disagree on the diagnosis of melanoma or its histopathologic staging, which may have implications for treatment and follow-up. For this reason, melanoma patients referred to Melanoma Institute Australia (MIA) for further treatment routinely have their pathology slides reviewed by MIA pathologists. This study sought to determine whether diagnosis, staging, and treatment of melanoma patients changed significantly after central pathology review. METHODS: A total of 5,011 pairs of non-MIA and MIA pathology reports on the same primary melanoma specimen were reviewed. Differences in diagnosis, American Joint Committee on Cancer (AJCC) T classification, and treatment recommendations based on the non-MIA and MIA pathology reports were determined. RESULTS: A melanoma diagnosis changed in 5.1 % of cases after review. Where both pathologists agreed on a diagnosis of melanoma, AJCC T classification changed in 22.1 % after review. After MIA review, planned surgical excision margins changed in 11.2 % of cases, and a recommendation for sentinel lymph node biopsy (SLNB) changed in 8.6 %. Non-MIA reports less frequently contained criteria to define AJCC T classification (86.6 vs. 97.6 %), select appropriate surgical excision margins (95.2 vs. 99.6 %) and make a recommendation for SLNB (94.5 vs. 99.4 %), (each p < 0.001). On multivariate analysis, partial biopsies were independently associated with more frequent changes in AJCC T classification (p < 0.001), planned surgical excision margins (p < 0.001), and SLNB recommendations (p < 0.001) on the basis of MIA pathology review. CONCLUSIONS: Diagnosis, AJCC T classification, and treatment recommendations often change after pathology review by specialist melanoma pathologists. We recommend pathology review be considered for all patients attending specialist melanoma treatment centers.

Reproducibility of AJCC staging parameters in primary cutaneous melanoma: an analysis of 4,924 cases.

BACKGROUND: Pathology reports are of critical importance for conveying information to clinicians who must make important management decisions for their patients. This study sought to assess and compare the precision, reproducibility, and completeness of external pathology reports and pathology reports generated by central review of each case in a large cohort of primary cutaneous melanoma patients. METHODS: Details of matched external pathology reports and corresponding review reports for 4,924 primary cutaneous invasive melanomas diagnosed and treated at Melanoma Institute Australia (MIA) between 2001 and 2011 were analyzed. RESULTS: Interobserver agreement was excellent for American Joint Committee on Cancer (AJCC) T staging parameters: Breslow thickness (intraclass correlation coefficient [ICC] 0.984), mitotic rate (ICC 0.833), and ulceration (kappa statistic [κ] 0.823). All three of these important pathologic variables were included in 92.4 and 66.9% of review (MIA) and external (non-MIA) pathology reports, respectively. Completeness of MIA and non-MIA pathology reports for the three essential T-staging criteria increased significantly from 87.9 to 94.6% (χ(2) = 9.1, df = 1, P = 0.003) and from 53.2 to 74.3% (χ(2) = 35.0, df = 1, P < 0.001) over the 10-year study period. The AJCC N staging parameter of microsatellites was recorded in only 43% of non-MIA reports and demonstrated moderate concordance (κ = 0.560). CONCLUSIONS: Reproducibility and completeness of pathology reports for many important histopathologic features have improved in recent years. Nevertheless, the documentation of microsatellites remained poor in external pathology reports. To enhance the usefulness of the pathology report for the provision of optimal melanoma patient care, continued efforts to encourage pathologists to document its key features appear warranted.

Four different treatment strategies in aggressive fibromatosis: A systematic review.

BACKGROUND: The treatment approach for aggressive fibromatosis is changing. Although surgery is the mainstay in common practice, recent literature is reporting a more conservative approach. We compared the local control rate for surgery, surgery with radiotherapy, radiotherapy alone and a wait and see policy in a systematic review. METHODS: A comprehensive search of the databases PubMed/Medline, Embase and Cochrane, of the medical literature published in 1999 till March 2017 was performed by two reviewers, including articles about extra abdominal aggressive fibromatosis without the genetical variants. A total of 671 studies were assessed for eligibility, and 37 studies were included for analysis, representing 2780 patients. RESULTS: The local control rates for surgery alone, surgery and radiotherapy, radiotherapy alone and observation were 75%, 78%, 85% and 78%, respectively. For patients with recurrent disease observation had a better local control rate than surgery alone (p = 0.001). In the observation group, stabilization of the tumor was seen in median 14 (range 12-35) months. The time to local recurrence in the treatment group was median 17 (range, 11-52) months. CONCLUSION: A watchful conservative first line approach with just observation and closely monitoring, by means of physical examination and MRI, appears to be justified in a subgroup of patients without clinical symptoms and no possible health hazards if the tumor would progress.

[A patient with a possible Mirizzi's syndrome]. / Een patiënt met een mogelijk mirizzi-syndroom.

BACKGROUND: Mirizzi's syndrome is a rare cause of jaundice. The syndrome refers to common hepatic duct obstruction or choledoch duct obstruction caused by extrinsic compression of an impacted stone in the gallbladder neck or cystic duct. CASE DESCRIPTION: A 42-year-old woman was referred to the emergency department with symptoms indicative of obstructive icterus. Endoscopic retrograde cholangiopancreatography (ERCP) and a CT scan revealed signs of Mirizzi's syndrome but no indications of malignancy. Laparoscopic cholecystectomy was decided upon. This procedure revealed that the obstruction was caused by a gallbladder carcinoma. CONCLUSION: Of those patients suspected of having Mirizzi's syndrome, retrospectively 5-28% prove to have carcinoma of the gallbladder. Therefore in Mirizzi's syndrome before carrying out laparoscopic cholecystectomy a careful diagnostic approach is essential. This includes ERCP or MRI cholangiopancreaticography (MRCP) and a CT scan. Even after these investigations the surgeon should only perform laparoscopic surgery with caution, as it is often converted to an open procedure and because of the risk of presence of a malignancy.