Measuring the depth of invasion in vulvar squamous cell carcinoma: interobserver agreement and pitfalls.

AIMS: The depth of invasion is an important prognostic factor for patients with vulvar squamous cell carcinoma (SCC). The threshold of 1 mm distinguishes between FIGO stages IA and ≥IB disease and guides the need for groin surgery. Therefore, high interobserver agreement is crucial. The conventional and the alternative method are described to measure the depth of invasion. The aims of this study were to assess interobserver agreement for classifying the depth of invasion using both methods and to identify pitfalls. METHODS AND RESULTS: Fifty slides of vulvar SCC with a depth of invasion approximately 1 mm were selected, digitally scanned and independently assessed by 10 pathologists working in a referral or oncology centre and four pathologists in training. The depth of invasion was measured using both the conventional and alternative method in each slide and categorised into ≤1 and >1 mm. The percentage of agreement and Light's kappa for multi-rater agreement were calculated, and 95% confidence intervals were calculated by bootstrapping (1000 runs). The agreement using the conventional method was moderate (κ = 0.57, 95% confidence interval = 0.45-0.68). The percentage of agreement among the participating pathologists using the conventional method was 85.0% versus 89.4% using the alternative method. Six pitfalls were identified: disagreement concerning which invasive nest is deepest, recognition of invasive growth and where it starts, curved surface, carcinoma situated on the edge of the tissue block, ulceration and different measurement methods. CONCLUSIONS: Pathologists reached only moderate agreement in determining the depth of invasion in vulvar SCC, without a notable difference between the two measurement methods.

Biological correlates of FDG uptake in non-small cell lung cancer.

PURPOSE: Each pathological stage of non-small cell lung cancer (NSCLC) consists of a heterogeneous population containing patients at much higher risk than others. Noninvasive functional imaging modalities, such as 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), could play a role in further characterization of NSCLCs. As many factors can influence the extent of FDG uptake, the underlying mechanisms for FDG accumulation in tumors, are still a matter of debate. The aim of the present study was to investigate these possible mechanisms in the primary site of early stage preoperatively untreated NSCLC. METHODS: 19 patients with early stage NSCLC, who had undergone both preoperative FDG-PET imaging and curative surgery, were enrolled in this study. Standardized uptake values (SUVs) were used for evaluation of primary tumor FDG uptake. Final diagnosis, tumor type, tumor cell differentiation and size of the primary tumors were confirmed histopathologically in resected specimens. Histologic sections were analyzed for amount of inflammation and necrosis. Expression of the glucose membrane transporters (GLUT-1 and GLUT-3); the isoforms of the glycolytic enzyme hexokinase (HK-I, HK-II and HK-III); and the cysteine protease caspase-3, was evaluated immunohistochemically. RESULTS: FDG uptake was significantly higher in squamous cell carcinomas (mean SUV 13.4+/-4.9, n=8) compared to adenocarcinomas (7.1+/-3.3, n=8, p=0.007), or large cell carcinomas (5.9+/-1.9, n=3, p=0.02). The degree of FDG accumulation seemed to depend especially on GLUT-1, GLUT-3 and tumor cell differentiation. The summed standardized values of these three parameters correlated significantly with the SUV (r=0.47, p=0.05). CONCLUSION: The present study supports the hypothesis that tumor cell differentiation in combination with overexpression of GLUT-1 and GLUT-3 determine the extent of FDG accumulation and that squamous cell carcinomas accumulate more FDG than adenocarcinomas or large cell carcinomas.

[Cryptococcal meningitis]. / Cryptokokkenmeningitis.

Immunocompromised patients are at increased risk of disseminated cryptococcal infection, often presenting as a primary respiratory infection with yeast cells originating from bird excreta. Because Cryptococcus neoformans has a tropism for cerebrospinal fluid, most patients suffer from meningitis or meningoencephalitis. Symptoms of cryptococcal meningitis are non-specific: headache, fever, nausea, or altered mental state and behaviour. Case descriptions of a renal transplant recipient and an HIV patient illustrate the non-specific presentation of cryptococcal meningitis. Lumbar puncture seemed to be critical in establishing the diagnosis. Cerebrospinal fluid, blood and other tissues were tested for C. neoformans by microscopy, culture and antigen tests. The patients were successfully treated with amphotericin B or liposomal amphotericin B intravenously and flucytosine intravenously or orally, followed by long-term fluconazole. The mortality rate for cryptococcal meningitis is 41% among renal transplant recipients and 20% in HIV patients.

Pulmonary sclerosing hemangioma detected by fluorodeoxyglucose positron emission tomography in familial adenomatous polyposis: report of a case.

We present a 53-year-old female suffering from familial adenomatous polyposis, who was found to have a positive nodus, lateral to the hilus of the left lung, on routine FDG-PET scan. This lesion was found to be a sclerosing hemangioma. We found an aberrant beta-catenin expression on immunohistochemical staining, suggesting that sclerosing hemangioma and familial adenomatous polyposis share the same pathophysiology. It is important to be aware of the association of familial adenomatous polyposis and sclerosing hemangioma.