Kenneth Jaaback

Positron emission tomography and granulosa cell tumor recurrence: a report of 2 cases.

Two case reports of women with recurrent granulosa cell tumors identified initially by increasing levels of inhibin. As part of their investigation to assess the extent of the recurrence, an abdominopelvic computed tomography and a positron emission tomography scans were performed. Interestingly, the recurrent tumors were identified on the abdominopelvic computed tomography but not on the positron emission tomography scan. These recurrences were confirmed at surgery, and the histopathologic findings were identical to the original lesion.

Risk Malignancy Index (RMI) in patients with abnormal pelvic mass: comparing RMI 1, 2 and 3 in an Australian population

Gynaecology oncology is one of the sub-specialities within the discipline of obstetrics and gynaecology and is now available in most major hospitals. With the availability of this service, it has become possible for the general obstetricians and gynaecologists to request assistance when performing difficult surgical procedures. These requests are usually from colleagues within the hospital but they can also be from gynaecologists in affiliated district hospitals. Patients presenting with a complex pelvic mass diagnosed by ultrasound imaging is a common cause of referral from gynaecologists in district hospitals. The main fear among gynaecologists in the peripheral hospitals is to inadvertently operate on a patient with a malignant tumour. There is now good evidence that patients with ovarian cancer have better outcomes if the primary surgery is performed by a qualified gynaecological oncologist. In the John Hunter Hospital, Hunter New England Centre for Gynaecological Cancer (a tertiary referral hospital), we accept referrals from gynaecologists in the peripheral hospitals and at times this can be a daunting task. While accommodating these referrals, it is important to have a system in place so as not to delay surgical intervention in patients with established gynaecological cancers. The use of a risk of malignancy index can identify patients at high risk of malignancy pre-operatively and thus allow appropriate triage. Appropriate use of the Risk Malignancy Index (RMI) has been shown to reduce the number of benign cases operated on in busy gynaecological oncology units. In 1990, Jacobs first described the Malignancy Risk Index, where he detailed the value of clinical features, realtime ultrasonography and serum CA 125 measurement in the diagnosis of patients admitted with a complex pelvic

Bilateral dysgerminoma associated with gonadoblastoma and sex-cord stromal tumour with annular tubules in a 28-year-old fertile woman with normal karyotype

8. Sahin AA, Ro JY, Chen J, Ayala AG. Spindle cell nodule and peptic ulcer arising in a fully developed gastric wall in a mature cystic teratoma. Arch Pathol Lab Med 1990; 114: 529–31. 9. Jung YC, Chen CJ, Tzeng CC. Melanosis peritonei associated with enteric duplication cyst. A case report. Am J Surg Pathol 1996; 20: 181–6. 10. Eide J. Pathogenesis of generalized melanosis with melanuria and melanoptysis secondary to malignant melanoma. Histopathology 1981; 5: 285–94. 11. Perez A, Turajlic S, Szyszko T, et al. Generalized melanosis and melanuria in a patient with metastatic melanoma.Clin Exp Dermatol 2010; 35: e37–9. 12. Busam KJ, Wolchok J, Jungbluth AA, Chapman P. Diffuse melanosis after chemotherapy-induced tumor lysis syndrome in a patient with metastatic melanoma. J Cutan Pathol 2004; 31: 274–80. 13. Murray C, D’Intino Y, MacCormick R, et al. Melanosis in association with metastatic malignant melanoma: report of a case and a unifying concept of pathogenesis. Am J Dermatopathol 1999; 21: 28–30.

Adipose-Derived VEGF–mTOR Signaling Promotes Endometrial Hyperplasia and Cancer: Implications for Obese Women

Obesity is responsible for increased morbidity and mortality in endometrial cancer. Despite the positive correlation of body mass index (BMI) or obesity in endometrial carcinogenesis, the contribution of adipose tissue to the pathogenesis of endometrial hyperplasia and cancer is unclear. This study clarifies the role of adipocytes in the pathogenesis of endometrial cancer by demonstrating that adipocyte-conditioned medium (ACM) increases proliferation, migration, and survival of endometrial cancer cells compared with preadipocyte-conditioned medium (PACM). Comparative cytokine array analysis of ACM and PACM reveal upregulation of a group of cytokines belonging to the VEGF signaling pathway in ACM. VEGF protein expression is upregulated in visceral adipose tissue (VAT) in obese patients, which is correlated with increased tumor growth in an in vivo xenograft model. The increased tumor size is mechanistically associated with the activation of the PI3K/AKT/mTOR pathway, a downstream target of VEGF signaling, and its suppression decreased the growth-promoting effects of VAT on endometrial cancer cells. Similar to the human model systems, pathologic changes in endometrial cells in a hyperphagic obese mouse model are associated with increased body weight and hyperactive mTOR signaling. Analysis of human tissue specimens depicts increased in tumor vasculature and VEGF-mTOR activity in obese endometrial cancer patients compared with nonobese patients. Collectively, these results provide evidence that VEGF-mTOR signaling drives endometrial cell growth leading to hyperplasia and cancer. Implications: Adipocyte-derived VEGF–mTOR signaling may be an attractive therapeutic target against endometrial cancer in obese women. Mol Cancer Res; 16(2); 309–21. ©2017 AACR.

Genetic changes correlate with histopathology in a benign, borderline and malignant mucinous ovarian tumour.

1 The Centre for Information-Based Medicine, Hunter Medical Research Institute, New Lambton Heights, and The Discipline of Medical Genetics, School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle, Callaghan, 2 School of Medicine and Public Health, University of Newcastle, Callaghan, 3 Hunter Centre for Gynaecological Cancer, John Hunter Hospital, New Lambton Heights, and 4 Division of Anatomical Pathology, Hunter Area Pathology Service, John Hunter Hospital, New Lambton Heights, NSW, Australia

Nucleotide excision repair protein ERCC1 and tumour-infiltrating lymphocytes are potential biomarkers of neoadjuvant platinum resistance in high grade serous ovarian cancer

OBJECTIVE ERCC1 is a nucleotide excision repair protein that may have a role in drug resistance in high grade serous ovarian cancer (HGSOC). We hypothesized that ERCC1 expression and tumour infiltrating lymphocytes (TILS) are induced by chemotherapy in HGSOC, which may be prognostically useful. METHODS 115 HGSOC patients were used for this study. 92 (80%) of the tissue analysed had not been exposed to platinum chemotherapy. The remaining 20% (n = 23) of cases received combination or monotherapy with carboplatin before tissue was collected. Immunohistochemistry was used to score for ERCC1 expression and morphology to score for TILs. Correlation analysis of all clinical parameters, TILs and ERCC1 and Kaplan-Meier survival analysis was performed using the ERCC1 and TILs scoring parameters (0, 1, 2 or 3). RESULTS ERCC1 expression was 2-fold higher in the neoadjuvant chemotherapy group compared to the primary cytoreductive surgery group (p < 0.0001). The mean overall survival for the neoadjuvant group with high ERCC1 was 141.6 ± 20.2 months which was significantly longer than absent ERCC1 survival of 61 + 22.6 months (p = 0.028). ERCC1 score strongly correlated with TILs score across the whole cohort (0.349, p = 1.3 × 10-4) suggesting there is a relationship between ERCC1 expression and TILs, but this requires further investigation. CONCLUSION In conclusion, ERCC1 was identified as a potential biomarker of platinum response overall survival in HGSOC undergoing neoadjuvant HGSOC treatment.