Anni Grove

Ovarian carcinoma histotype determination is highly reproducible, and is improved through the use of immunohistochemistry

To assess the variation in ovarian carcinoma type diagnosis among gynaecological pathologists from Nordic countries, and whether a rationally designed panel of immunohistochemical markers could improve diagnostic reproducibility.

Immunohistochemical Expression of Wilms Tumor Gene Protein in Different Histologic Subtypes of Ovarian Carcinomas

CONTEXT Immunohistochemical expression of Wilms tumor gene protein (WT1) has previously been described in primary ovarian carcinomas. OBJECTIVE To evaluate differences in WT1 expression among different histologic subtypes of ovarian carcinomas and the correlation to the histologic grade. DESIGN Ninety-one primary ovarian carcinomas were reviewed, and 1 representative formalin-fixed and paraffin-embedded tissue block was selected. One slide from each case included in the study was immunostained using the WT1 clone 6F-D2. The immunoreactivity was graded according to the percentage of stained tumor cells. Only nuclear staining was considered a positive reaction. A tumor was regarded as negative if less than 1% of the tumor cells was stained. RESULTS All serous carcinomas (28/28) showed WT1 expression, whereas all mucinous (14/14) and all clear cell carcinomas (14/14) were negative. The lone malignant Brenner tumor and 3 (60%) of 5 undifferentiated carcinomas included in the study were also negative. The endometrioid carcinomas showed either no reaction for WT1 or were diffusely positive with more than 50% of the tumor cells stained. All the grade 1 tumors (10/10) were negative, whereas 5 (45%) of the 11 grade 2 tumors and 5 (63%) of the 8 grade 3 tumors showed a positive reaction. CONCLUSION The present study demonstrates differences in immunohistochemical expression of WT1 among different histologic subtypes of primary ovarian carcinomas. Regarding the endometrioid subtype, the expression seems to be correlated to the histologic grade.

Mesotheliomas of the tunica vaginalis testis and hernial sacs

Three histologically and immunohistochemically well-documented cases of mesothelioma of the tunica vaginalis testis and hernial sac are presented. Analysis and follow-up data on our three patients and a review of 30 previously reported cases have revealed a varied and often unpredictable clinical course. A classification into high- and lowgrade malignant tumours is suggested, based on clinical and pathological findings.

Improved classification of epithelial ovarian cancer: results of 3 danish cohorts

Objective An increasing body of evidence has suggested that epithelial ovarian cancer (EOC) patients can broadly be divided into 2 groups on the basis of histopathologic parameters and molecular profiles. Type 1 tumors are slow-growing tumors with inherent mutations such as KRAS or BRAF mutations, whereas type 2 tumors are more rapidly growing tumors of which many contain TP53 mutations. In the present study, we performed a comprehensive study in a large Danish material to evaluate the clinical importance. Materials and Methods A total of 512 tissue samples were included (430 EOCs, 34 borderline, 28 benign tumors, and 20 normal ovaries). KRAS mutations (codon 12/13) and BRAF codon 600 mutations were analyzed from formalin-fixed paraffin-embedded tissue by ARMS qPCR. p53 expression was examined by immunohistochemistry. Results Of the EOC patients, 25% had histopathologically classified type 1 tumors, and of these, 44% were either KRAS or BRAF mutated. Of patients with histopathologic type 2 tumors, 66% showed p53 protein overexpression, whereas 4 (1.5%) patients contained a KRAS mutation. In a univariate survival analysis, a large difference in survival was seen between patients with type 1 and type 2 tumors. Patients with type histologic 2 tumors had significantly worse survival compared with patients with type 1 tumors (P < 10−5). International Federation of Gynecology and Obstetrics (FIGO) stage, tumor grade, residual tumor, and KRAS/BRAF mutation were independent predictors of overall survival in the multivariate analysis. Patients with KRAS/BRAF mutated carcinomas showed independent decreased overall survival with a hazard ratio of 2.01 (95% confidence interval, 1.13–3.57; P = 0.018). Conclusions KRAS/BRAF mutations are with very few exceptions constrained to patients with histopathologic type 1 tumors, whereas p53 overexpression is very frequent in type 2 tumors. KRAS/BRAF mutations had independent prognostic importance. The classification presented here should have a major therapeutic implication and serve as a hallmark of future clinical trials.

Focal fatty change of the liver. A review and a case associated with continuous ambulatory peritoneal dialysis

Focal fatty change (FFC) of a liver with unequivocal normal architecture is rare. A review of the literature revealed 39 histologically well-documented cases. Well-known steatogenic conditions were present in most of these cases. Focal ischaemia or a varying rate of mobilization of fat in the liver have been suggested as a cause of the focality of the lesions. FFC occurring in a diabetic patient on continuous ambulatory peritoneal dialysis (CAPD) is presented. The FFC in this and in ten previously reported cases associated with CAPD and intraperitoneal insulin therapy had a unique subcapsular distribution, which may suggest a specific pathogenetic mechanism involving insulin. The clinical significance of FFC in the differential diagnosis from other fatty lesions of the liver is summarized.

Estrogen and progesterone receptors in epithelial ovarian tumours

A study of the estrogen receptor (ER) and progesterone receptor (PR) status and content in 43 patients with histologically proven primary epithelial ovarian tumours was undertaken. The results of ER and PR status in 604 primary epithelial ovarian carcinomas of different histological types were analyzed in a combined material collected from the literature (576 cases) and 28 cases from our own study. Statistical analysis showed significant difference in ER status, but not in PR status, between the different histological types. The highest proportion of ER positive tumours was found among the serous and endometrioid types. Thus when analysing the correlation of ER status with other parameters in ovarian cancer, histological type should be taken into account. In 3 benign, 4 borderline and 14 malignant serous ovarian tumours no statistically significant difference was found in steroid receptor content and status. In 11 patients with multiple tumour locations, only two patients with mixed serous/endometrioid malignant tumours had different receptor status in different tumour locations.

Benign multicystic peritoneal mesothelioma.

A 40-year-old woman (para 5) was referred to hospital because of intermittent lower abdominal pain and an increasing pelvic mass. She had a clinical history of two stillbirths, a cesarean section and sterilization. Ultrasonography (US) of the abdomen revealed a small quantity of ascitic fluid and a unilocular cystic process in the right abdomen measuring 10cm. It was characterized as an ovarian cyst. At laparoscopy the uterus and adnexa were normal. The pouch of Douglas was filled with a free-floating, loose, folded and thin-walled cyst which was excised. Recovery from surgery was uneventful.

Superficial perineal leiomyosarcoma in an adolescent female and a review of the literature including vulvar leiomyosarcomas.

Superficial perineal leiomyosarcomas are rare, with only three previously reported examples. We encountered a superficial (deep subcutaneous) perineal leiomyosarcoma in a 17‐year‐old female. At follow‐up two years after a wide excision, there were no signs of recurrence. The tumour was well differentiated and showed immunoreactivity for alpha‐smooth muscle actin and desmin. A review of the literature on superficial leiomyosarcomas indicates that superficial perineal leiomyosarcomas may be more aggressive than superficial leiomyosarcomas in general. As the presented tumour occurred in a female, it was compared with vulvar leiomyosarcomas.

Amylase in lung carcinomas

The ultrastructure of two lung adenocarcinomas with immunohistochemical and biochemical expression of amylase is reported. Isoenzyme determination performed on tumour tissue showed a salivary‐type amylase. None of the carcinomas was associated with hyperamylasaemia. Ultrastruc‐turally, the adenocarcinomas contained a varying number of heterogeneous granules resembling lysosomes. None of the tumours contained mature zymogen granules. The findings are discussed in relation to previous cases of amylase‐containing lung carcinomas subjected to electron microscopy. The vast majority of these carcinomas were associated with a significant elevation of serum amylase. Various theories which might explain the absence of hyperamylasaemia in the presented cases are proposed. The biological and diagnostic significance of amylase production is discussed.

Lymphadenectomy in surgical stage I epithelial ovarian cancer

To identify the extent of lymphadenectomy performed in women presenting with epithelial ovarian cancer macroscopically confined to the ovary. Furthermore, the effect of lymphadenectomy on overall survival is evaluated.