Evaluation of a nationwide Dutch guideline to detect Lynch syndrome in patients with endometrial cancer.

OBJECTIVE: In the Netherlands a nationwide guideline was introduced in 2016, which recommended routine Lynch syndrome screening (LSS) for all women with endometrial cancer (EC) <70 years of age. LSS consists of immunohistochemical (IHC) staining for loss of mismatch repair (MMR) protein expression, supplemented with MLH1 methylation analysis if indicated. Test results are evaluated by the treating gynaecologist, who refers eligible patients to a clinical geneticist. We evaluated the implementation of this guideline. METHODS: From the nation-wide pathology database we selected all women diagnosed with EC < 70 years of age, treated from 1.6.2016-1.6.2017 in 14 hospitals. We collected data on the results of LSS and follow up of cases with suspected LS. RESULTS: In 183 out of 204 tumours (90%) LSS was performed. In 41 cases (22%) MMR protein expression was lost, in 25 cases due to hypermethylation of the MLH1 promotor. One patient was known with a pathogenic MLH1 variant. The option of genetic counselling was discussed with 12 of the 15 remaining patients, of whom three declined. After counselling by the genetic counsellor nine patients underwent germline testing. In two no pathogenic germline variant was detected, two were diagnosed with a pathogenic PMS2 variant, and five with a pathogenic MSH6 variant, in concordance with the IHC profiles. CONCLUSION: Coverage of LSS was high (90%), though referral for genetic counselling could be improved. Gynaecologists ought to be aware of the benefits and possible drawbacks of knowing mutational status, and require training in discussing this with their patients.

Vulvar mucinous adenocarcinoma with neuroendocrine differentiation: A case report and review of the literature.

BACKGROUND: There are limited cases in literature of patients with mucinous adenocarcinoma of the vulva with neuroendocrine differentiation have. With this new case, we aim to provide an overview of the existing literature and present a tool with relevant markers for the pathologist in the differential diagnosis. CASE DESCRIPTION: A 92-year-old multiparous, Caucasian woman presented with a 8 cm spherical tumor of the left major labium. Since the initial punch biopsy was not conclusive, a local resection was performed. Histopathological examination showed mucus production, large pools of mucin with trabeculae and cribriform glandular structures with strongly atypical columnar epithelium. Additional immunohistochemical analysis demonstrated expression of: CEA, CK7, EMA, and the neuroendocrine markers synaptophysin and chromogranin supporting the diagnosis. CONCLUSION: In this report, we present a new case of a mucinous adenocarcinoma of the vulva with neuroendocrine differentiation based immunohistochemical analysis. Due to the indolent tumor behavior, partial vulvectomy is the therapy of choice.

Lymph node examination among patients with gastric cancer: variation between departments of pathology and prognostic impact of lymph node ratio.

INTRODUCTION: At least 15 lymph nodes should be retrieved for proper TNM-staging in gastric cancer. We evaluated nodal harvest and examined its relation to stage distribution and survival at a population-based level, including the value of N-ratio (metastatic/evaluated) as a staging modality. METHODS: All patients resected for primary M0 gastric cancer diagnosed in 1999-2007 in the Dutch Eindhoven Cancer Registry area were included (N = 880). Determinants of lymph node evaluation and their relationship with stage and survival were assessed in multivariable regression analyses. N-ratio categories were determined (N-ratio 0, 0%; N-ratio 1, 0.1%-19%; N-ratio 2, 20%-29%; N-ratio 3, ≥30%) RESULTS: The median number of lymph nodes examined was 7, dependent on N-category (N0: 7; N+: 8). It varied between departments of pathology from 5 to 9. This variation remained after adjustment for relevant patient- and tumour factors. Stage distribution differed between pathology departments (proportion N0 ranging from 14% to 21%, p = 0.003). Among resected patients with N0M0 disease and <7 nodes examined, 5-year survival was 56%, compared to 69% among patients with ≥7 nodes examined (p = 0.012). Five-year survival for N-ratio 0 was 58%, N-ratio 1 50%, N-ratio 2 18% and N-ratio 3 11% (p < 0.0001), while 5-year survival ranged from 58% for N0, 17% for N1, and 11% for N2/3 (p < 0.0001). CONCLUSION: In this series of patients with a relatively low number of evaluated lymph nodes, a high prognostic accuracy of N-ratio was found. However, improvement in nodal assessment is mandatory.