A clinicopathological study of granulosa cell tumors of the ovary: Can morphology predict prognosis?

Objective: Granulosa cell tumors (GCT) are low-grade malignant sex cord-stromal tumors (SCST) with late metastasis/recurrences and long disease-free periods. We performed a clinicopathological evaluation of GCT to ascertain features having prognostic impact. Materials and Methods: All cases of GCT of ovary from January 2006 to December 2018 were assessed for architectural patterns, nuclear grooves, and Call-Exner bodies. Each feature was graded on frequency of occurrence: not present (0)–very frequent (3). Anisonucleosis, necrosis, and inflammation were noted. Cases were grouped on mitotic count; <10 mitosis/10 High power field (HPF) or >=11 mitoses/10 HPF and Ki-67 index; <10% Ki-67 and >=11% Ki-67. Results: GCT formed 60.1% of SCST. Sixty cases' ages were in the range of 15–78 years (median 45). Clinical details were available in 37. Commonest presentation was abnormal uterine bleeding. Serum CA125 was raised in 16.1% and Inhibin in 58.8%. Seventy percent were in stage I. Disease recurrence was associated with higher stage (P = 0.007). The most frequent pattern was diffuse sheets (47%). Call-Exner bodies were absent in 22.2%. Grooves with score 1, 2, and 3 were seen in 35.8%, 23.5%, and 13.6%, respectively. Anisonucleosis was present in 26.7%, necrosis in 11.1%, and lympho-plasmacytic infiltrate in 43%. Out of total, 93.3% had <10 mitosis/10 HPF and 43.2% had recurrence, most with high Ki-67 (P = 0.064). Conclusion: Our study outlines histomorphological spectrum of GCT and emphasizes its frequent occurrence in lower stages with late recurrences. The presence of grooves may indicate granulosa-cell origin. Call-Exner bodies are not a necessity. Histomorphological features are not prognostically important. However, prognostic value of Ki-67 cannot be excluded. Limitation of the study was a small number of cases with follow-up.

Oral metronomic chemotherapy for recurrent & refractory epithelial ovarian cancer: A retrospective analysis

Background & objectives: Advanced epithelial ovarian cancer (EOC) is associated with dismal outcome and progression-free survival (PFS) shortens with each subsequent relapse. For patients with recurrent and platinum refractory disease, therapeutic options are limited. Oral metronomic therapy (OMT) is associated with symptomatic relief and stable response in a significant proportion of patients. We retrospectively evaluated the outcome of patients with EOC treated with OMT at a tertiary care hospital in north India. Methods: Between January 2011 to December 2017, 36 EOC patients received OMT. Patients' median age was 50 yr (range, 38-81 yr) and they had received a median of two lines of prior chemotherapy. OMT regimen included a combination of cyclophosphamide, etoposide (VP-16) and celecoxib with or without pazopanib along with supportive care. Response rates and outcomes were ascertained using the Gynecological Cancer Intergroup Guidelines. The toxicity was graded according to the Common Terminology Criteria for Adverse Events v.4.03. Results: The median CA-125 before initiating OMT was 160 U/ml (range, 42.23-5330 U/ml). The median interval between last chemotherapy and starting OMT regimen was 159 days (range, 1-1211 days). The overall response rate was 50 per cent. The median progression-free survival (PFS) was 8.2 months [95% confidence interval (CI): 5.03-10.33], and the median overall survival was 38 months (95% CI: 25.6-NR). Patients who received two lines of chemotherapy before OMT (P=0.052) and those who received pazopanib-based OMT (P=0.0513) had better PFS. Interpretation & conclusions: For patients with relapse and refractory EOC, OMT could be a reasonable option. A combination of oral etoposide (VP-16) and pazopanib needs further evaluation in a large number of patients in a randomized trial.

Evaluation of endometrial changes and p53 expression in tamoxifen treated women: comparison of various methods.

OBJECTIVE: To compare transvaginal sonography (TVS), sonohysterography (SHG), hysteroscopy and endometrial aspiration (EA) and p53 expression in assessing endometrial abnormalities in women on tamoxifen. METHODS: In a cross sectional study of 50 pre- and post-menopausal women receiving tamoxifen for > 2 years, all participants underwent TVS and EA. Those with endometrial thickness > 4 mm on TVS underwent hysteroscopy and SHG. Serum p53 antibody and p53 immunohistochemistry were tested in all women. RESULTS: The sensitivity and specificity when compared with histopathology as the reference standard were as follows: TVS 100% and 33.3%, SHG 85.7% and 50%, hysteroscopy 92.8% and 80.8%, serum p53 50% and 83.3%, and p53 immunohistochemistry 57.1% and 61.1%. Prevalence of endometrial abnormalities was not significantly different in asymptomatic and symptomatic women. CONCLUSION: Tamoxifen-users require routine testing for endometrial evaluation. TVS followed by hysteroscopy and biopsy is an effective option. p53 expression correlates with histological abnormalities.

Visual inspection for cervical cancer screening: evaluation by doctor versus paramedical worker.

BACKGROUND: In the absence of an effective cervical cancer screening programme, efforts are being made to explore the feasibility of using the existing infrastructure to develop effective low-cost screening methods. AIMS: To evaluate and compare test performance of visual inspection of the cervix by a doctor and a paramedical worker. SETTING AND DESIGN: Gynaecology outpatient department (OPD), All India Institute of Medical Sciences, New Delhi; cross-sectional study. MATERIAL AND METHODS: One hundred women with complaints of vaginal discharge, irregular bleeding, post coital bleeding or unhealthy cervix underwent visual inspection with acetic acid (VIA) and Lugol's iodine (VILI) by a doctor and nurse, followed by colposcopy and biopsy. STATISTICAL ANALYSIS USED: Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for each test and compared. Concordance was determined by kappa statistics. RESULTS: VIA by nurse had a higher sensitivity (100% versus 87.5%), but lower specificity (53% versus 63%) when compared with the doctor, but it was not statistically significant. There was moderate agreement between their VIA findings (kappa=0.56). VILI findings were comparable to that of the VIA, both by the doctor and nurse. There was almost perfect agreement (kappa=0.89) between VILI by the doctor and nurse. CONCLUSION: Visual inspection can be performed reliably by trained paramedical workers and doctors and is an effective screening option in low resource settings.

Successful pregnancy outcome in advanced chronic renal failure.

A 24 years female of advanced chronic renal failure due to lupus nephritis presented with pregnancy of eight weeks duration she continued the pregnancy against medical advice. At 29 weeks gestation further deterioration of renal function prompted weekly dialysis and hospitalisation for intensive maternal and fetal monitoring. At 35 weeks she was safely delivered by elective caesarian section. This is the first case of dialysis during pregnancy to be reported from India.

Idiopathic origin of meconium peritonitis.

A 26-year-old, gravida 3 presented at 31 weeks of gestation with polyhydramnios. On ultrasound there was marked foetal ascitis with unilateral hydrocele. Patient delivered a 3.15 kg, large-for-date baby at 33 weeks and 3 days of gestation. On basis of clinical, radiological and sonographic features, diagnosis of meconium peritonitis was made. Ascitic tapping was done. Surgery was withheld, as there were no signs of intestinal obstruction. DNA testing for cystic fibrosis was negative. Baby did not deteriorate so he was discharged. Baby was doing well on 2 months follow up. Hydrocele and ascitis were resolving. Rarely meconium peritonitis may occur without an underlying cause when peritonitis may be innocuous and intervention may not be required.

Correlation of radiological and pathological assessment of tumour volume with lymph node involvement in cancer cervix.

The present study was carried out in 18 patients with carcinoma cervix stage IB through early IIB-Preoperative computerised tomography (C.T.) was done within seven days before surgery. Volume of tumour was determined from the C. T. films. Radical hysterectomy Type-III was performed in all 18 patients and specimens of cervix, parametrium and lymph nodes subjected to histopathological examination. Each specimen of cervix was cut into 4 to 12 equal sections depending on the size of the tumour mass. Cervical tumour volume was measured. Correlation of radiological with pathological tumour volume and of tumour volume with lymph node involvement was done. C. T. Scan was able to detect tumour mass accurately only four patients (Sensitivity 40%, Specificity 28.5%). In the Indian setting the conventional surgical approach appears to be the more appropriate.

Correlation of computed tomography with second-look laparotomy in ovarian carcinoma.

BACKGROUND: Cancer of the ovary is the second commonest gynaecological malignancy after cancer of the cervix. Surgery followed by cisplatin-based chemotherapy is the standard treatment approach. In patients with persistent disease, second-look laparotomy offers an opportunity to debulk the tumour. This is usually followed by an alternative method of chemotherapy. We compared the findings at surgery (second-look laparotomy) with the preoperative computed axial tomography scan assessments. METHODS: Thirty-seven patients with epithelial ovarian carcinoma were assessed with computed axial tomography scans of the abdomen and pelvis prior to undergoing a second-look laparotomy. RESULTS: Tumour was correctly identified on computed axial tomography scan in 11 patients who had macroscopic evidence of cancer at laparotomy. In 6 patients, both computed axial tomography scan and surgery showed no disease recurrence. In the remaining 20 patients, there was a mismatch between the computed axial tomography scan and the surgical findings. In 16 of the 20 (80%) patients, computed axial tomography scans were negative but tumour was present. When the tumour was less than 1.5 cm in diameter it was missed in 8, and when equal to or greater than 1.5 cm, it was missed in 5 patients. These small tumour deposits were located in the retroperitoneal area, under the dome of the diaphragm, omentum or peritoneum, liver surface, and in the pouch of Douglas. In one case each, infiltration of the urinary bladder, sigmoid colon and rectum was also not detected. In 4 patients, computed axial tomography scans showed tumour when none was present. CONCLUSION: Computed axial tomography scan cannot detect small nodules often present in ovarian cancer, and thus even if a computed axial tomography scan is normal it should not exclude a second-look laparotomy.

Tamoxifen increases the proliferation of human endometrial stromal cells in in vitro. A model for evaluation of endometrial hyperplasia.

Tamoxifen given for breast cancer therapy, has a complex and an unclear action on the endometrium. A large number of literatures has attributed the proliferous changes in the endometrium caused by tamoxifen (Tam). No report has appeared on the endometrial cellular changes induced by Tam. The present study shows a significant (P < 0.001) increase in the proliferative activity due to Tam in endometrial stromal cells over control and estradiol (E2). This in vitro model is useful for the study of the hyperplasic effect of Tam at the cellular level.

Pregnancy with idiopathic thrombocytopenic purpura.

The management of ITP in pregnancy remains controversial, particularly with reference to labour management. Thirteen pregnancies in 9 women with ITP are analysed with respect to maternal and neonatal outcome. One pregnancy culminated in spontaneous abortion. Ten infants were born by vaginal delivery and two by Caesarean section. There were no maternal or perinatal deaths. Maternal morbidity was not increased significantly due to ITP and none of the infants had purpuric manifestations even with low platelet counts. It is concluded that the obstetric management of these patients should be individualised and should not be based on platelet count alone.