Analysis of patients with endometrial carcinoma using the ProMise classifier: a pilot study from India.

BACKGROUND: Molecular subtyping of endometrial carcinomas (EC) has been shown to classify tumors into prognostically relevant groups. Characterizing EC with a limited number of markers viz., POLE mutations, p53 mutations, and MMR status, can provide valuable information. DESIGN: Paraffin sections of a cohort of 48 EC from a tertiary care center were characterized for the above-mentioned molecular markers and analyzed in the context of survival. METHODS: Formalin fixed paraffin embedded tissues from 48 EC were characterized for POLE mutations by Sanger sequencing (exons 9-14), for MMR (MLH1, MH2, MSH6) using immunohistochemistry (IHC) and copy number (high/low) using p53 IHC. Mutational status was integrated along with the clinicopathological details and survival analysis performed. RESULTS: Eleven (22.9%) patients were MMR deficient, 3 (6.3%) had POLE mutation, while 2 (4.1%) had both POLE and P53 mutations (regarded as multiple classifiers). Twelve (25%) patients were found to have P53 mutations, while the remaining 20 (41.7%) had no specific molecular profile (NSMP). Median follow-up duration was 43.5 (2-62) months with 8 recurrences and 9 deaths. Tumors with POLE mutation had the most favorable prognosis followed by the NSMP and the MMR mutated group while the P53 and multiple classifier groups had the worst prognosis in terms of OS (Log-rank p: 0.006) and PFS (Log-rank p: 0.001). CONCLUSION: The integration of molecular-clinicopathologic data for endometrial cancer classification, through cost-effective, clinically applicable assays appears to be a highly objective tool that can be adopted even in resource-limited settings. It has the potential to cause a shift in the paradigm of EC pathology and management practice.

The clinico pathological features and survival in serous endometrial cancers.

Background & Introduction: Serous cancers are a biologically aggressive variety of endometrial cancer (EC) with a high rate of recurrence and mortality among all the subtypes. Herein we describe our experience with serous endometrial cancer. Objective: This study was conducted to identify the clinicopathological characteristics, treatment modalities and survival outcomes in women diagnosed with serous endometrial malignancies. Methods: This was a retrospective descriptive analysis of data on patients diagnosed with serous endometrial tumours between January 2010 to September 2019 in our institute collected from electronic medical records. Descriptive statistics such as proportions, means and standard deviations and Cox regression hazards model on risk factors were performed. Survival was plotted by Kaplan-Meier curves. Results: During the study period, 32 (5.7%) patients out of 564 diagnosed cases of endometrial cancer had serous histology. The mean age at diagnosis was 62.5 years (SD 7.6) while mean BMI was 26.4 kg/m2 (SD 4.6). Staging laparotomy was done in 27(84%) of the patients. Advanced stages (III and IV) were detected in 16 patients (50%) at primary surgery.Adjuvant chemo therapy and radiation was received by 21(65.6%) patients therapy. Out of 32 patients, 13 (40%) developed recurrence while another 13 expired. Stage at diagnosis and type of adjuvant therapy were important factors in determining the outcome. Median recurrence free and overall survival was 22(95% CI 1.4-42) and 36 months (95% CI 10.1-61.8) respectively. Conclusion: Serous endometrial cancers are an intrusive subtype of EC. Comprehensive surgical staging with optimal cytoreduction should be aimed at. Adequate upfront molecular categorization of these tumors is mandated. Adjuvant therapy with chemotherapy and radiation is given in postoperative setting. Targeted therapies and immunotherapy could be considered in recurrences.

Malignant metastatic steroid cell tumor NOS: A rare presentation of a subtype of sex cord stromal tumor.

Steroid cell tumors - not otherwise specified (NOS) - are rare sex cord stromal tumors that lack characteristic histology, are benign, and usually present with androgenic manifestations. Metastatic malignant steroid cell tumors pose treatment challenges due to their chemoresistance nature. This is a case report of a metastatic steroid cell tumor - NOS with extensive peritoneal disease.

Comprehensive genomic profiling: Does timing matter?

Purpose: There is variability in utilization of Comprehensive Genomic Profiling (CGP) in most of the metastatic solid tumors (MST). We evaluated the CGP utilization patterns and its impact on outcomes at an academic tertiary center. Patients and Methods: Institutional database was reviewed for CGP data in adult patients with MST between 01/2012 - 04/2020. Patients were categorized based on interval between CGP and metastatic diagnosis; 3 tertiles of distribution (T1-earliest to the diagnosis, T3-furthest), and pre-mets (CGP performed prior to diagnosis of metastasis). Overall survival (OS) was estimated from the time of metastatic diagnosis with left truncation at the time of CGP. Cox regression model was used to estimate the impact of timing of CGP on survival. Results: Among 1,358 patients, 710 were female, 1,109 Caucasian, 186 Afro-Americans, and 36 Hispanic. The common histologies were lung cancer (254; 19%), colorectal cancer (203; 15%), gynecologic cancers (121; 8.9%), and pancreatic cancer (106; 7.8%). Time interval between diagnosis of metastatic disease and CGP was not statistically significantly different based on sex, race and ethnicity after adjusting for histologic diagnoses with 2 exceptions - Hispanics with lung cancer had delayed CGP compared to non-Hispanics (p =0.019) and females with pancreas cancer had delayed CGP compared to males (p =0.025). Lung cancer, gastro-esophageal cancer and gynecologic malignancies had better survival if they had CGP performed during the first tertile after metastatic diagnosis. Conclusion: CGP utilization across cancer types was equitable irrespective of sex, race and ethnicity. Early CGP after metastatic diagnosis might have effect on treatment delivery and clinical outcomes in cancer type with more actionable targets.

Platinum-Pemetrexed Chemotherapy for Recurrent Ovarian Cancer (ROC): A Single Center Experience.

In this retrospective analysis of 36 patients with recurrent ovarian cancer (ROC) treated with platinum pemetrexed doublet ± bevacizumab, the median age was 54.5 years (47-60) and 33 (91.7%) had serous histology. The overall response rate [ORR = complete (CR)+partial (PR) response] was 83.3%. At a median follow-up of 16 months, the median PFS was 13.8 months (95% CI: 10.849-20.580) and median OS 30.6 months, (95% CI: 21.46 months-NR). The incidence of Grade 3/4 anemia, thrombocytopenia, neutropenia and non-hematological toxicity was 19.4%, 3.9%, 16.6%, and 8.3%. Platinum pemetrexed chemotherapy in ROC is safe and effective treatment option.

Successful management of small cell neuroendocrine carcinoma of the ureter with neoadjuvant chemotherapy and adjuvant chemoradiation: case report and literature review.

Neuroendocrine tumours (NETs) of the urinary tract are rare, and the urinary bladder is the the most common primary site. Primary ureteric NET is rarer with under 80 cases reported in the literature thus far. Most of these tumours are of the high-grade small cell neuroendocrine carcinoma subtype, which has a worse prognosis. Neoadjuvant chemotherapy has a proven role in the management of NET of the bladder as it downstages the tumour, which may add to significant recurrence-free survival and overall survival. We report the successful management of a patient with locally advanced small cell neuroendocrine carcinoma of the ureter, who had a pathological complete response after neoadjuvant chemotherapy with etoposide and cisplatin. He subsequently received adjuvant chemotherapy followed by radiation and is recurrence-free at a follow-up of 1 year.

Metastatic Tumors to the Ovary-a Surgeon's Dilemma.

The ovary is a common site of metastasis. Differential diagnosis of ovarian carcinomas, including secondary tumors, remains a challenging task. Clinical decision-making depends on an accurate diagnosis of the type of ovarian cancer. This study was done to evaluate the pattern of metastatic tumors to the ovary and clinical details and to analyze the survival outcomes over a period of 5 years. Patients who had metastatic tumors to the ovary are identified from the electronic database from 1 January 2015 to 30 September 2019. Clinical details are collected from the electronic charts. Survival data is collected over the phone. The total number of ovarian cancers treated during the time period was 720, of which primary high-grade mucinous tumors contributed 9 (1.2%), and metastatic tumors to ovary 70 (10%). The highest levels of CEA were seen in carcinoma rectum, colon, and cholangiocarcinoma. CA 19-9 was very high in carcinoma gall bladder, pancreas, and cholangiocarcinoma. Common primaries were stomach (23%), gall bladder (13%), and colon (13%). Adenocarcinoma with signet ring cells was found in 29% of the patients. The median follow-up was 7 months (range 1 to 40 months). The median overall survival was 10 months after diagnosis (95% CI,7.9-12.0). There was no statistically significant difference in survival between patients who had peritoneal carcinomatosis with enlarged ovaries and those who had metastasis confined to ovaries (p value 0.360). A diagnosis of metastatic tumors to the ovary is associated with a very poor prognosis and the focus of treatment should be to improve the quality of life. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13193-020-01267-4.

Primary mediastinal germ cell tumours: real world experience in the low middle income (LMIC) setting.

PURPOSE: Primary mediastinal germ cell tumours (PMGCTs) are rare; with limited data available about their outcomes and optimal treatment in the low middle income countries setting. We studied the clinical profile of patients with PMGCT treated at our centre in order to estimate their survival outcomes and to identify prognostic factors affecting the same. PATIENTS AND METHODS: Fifty-seven patients with PMGCTs treated between April 2001 and June 2019 were included. Baseline characteristics, details of first line chemotherapy, response rates, toxicity and surgical outcomes were noted. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. RESULTS: Among 57 male patients (seminoma = 20 and nonseminomatous = 37), the median follow-up was 10 months (range: 1-120 months). For mediastinal seminoma, 9 (45%) and 11 (55%) patients had good and intermediate risk disease, respectively. Nineteen patients (95%) received BEP (Bleomycin, etoposide and cisplatin) chemotherapy. 94.7% had partial responses and median event-free survival was not reached. All patients were alive and disease free at 2 years. For primary mediastinal nonseminomatous germ cell tumours (PMNSGCTs), all patients were poor risk. Thirty-four (91.8%) received BEP/EP chemotherapy as first line. Responses were PRM+ (partial response with elevated markers) in 7 (20.5%) and PRM- in 12 (35.2%). The incidence of febrile neutropenia was 50% and 55.8% in seminole and PMNSGCT, respectively. The median OS was 9.06 months and median PFS was 4.63 months for PMNSGCT. The proportion of patients alive at 1 year and 2 years were 35% and 24.3%, respectively. CONCLUSION: Primary mediastinal seminomas are rarer and have better survival outcomes. Treatment of PMNSGCT is still a challenge and is associated with poorer survival outcomes.

Laparoscopic resection of a large mixed epithelial-stromal tumour of the seminal vesicle: a rare entity and review of the current literature.

Mixed epithelial-stromal tumours (MESTs) of the seminal vesicle (SV) are a rare neoplasm, with biological behaviour ranging from benign to malignant. Due to their rarity, there are no established guidelines for their treatment. We report a 37-year-old man with a large MEST of the SV which was successfully resected by laparoscopic transperitoneal approach. Amidst the controversy regarding the nomenclature and grading of MESTs in literature, we reclassified the previous reports of MESTs incorporating both the WHO and Reikie et al grading.

Numb Chin Syndrome as the Initial Manifestation of Breast Carcinoma.

Numb chin syndrome may be the manifestation of a local dental pathology or secondary to a systemic disease. A systematic physical examination with diagnostic workup is of utmost importance in patients presenting with numb chin syndrome. We report the case of a 58-year-old woman who presented with numb chin syndrome. An orthopantogram and computed tomography of the head revealed osteolytic lesion in the left molar region. Histopathological and immunohistochemical examination confirmed the lesion to be metastatic breast carcinoma. Breast ultrasound scan demonstrated a 1.5 × 1.5-cm lesion in the left breast and fine needle aspiration cytology from the lesion confirmed the diagnosis of breast carcinoma. Bone scan showed multiple bone metastases. She was diagnosed to have numb chin syndrome secondary to bone metastases from breast carcinoma. In view of her disseminated disease status, she was started on palliative hormone therapy (Letrozole) with zoledronic acid. We present this case to highlight the importance of careful evaluation of patients presenting with numb chin syndrome because this may be the only manifestation of a systemic malignancy.

Case of hepatic portal venous gas in an infant with hypertrophic pyloric stenosis.

Hepatic portal venous gas is the presence of gas within the portal vein and its branches. A 4-week-old male infant presented with 1-week history of non-bloody, non-bilious projectile emesis. Examination was significant for an olive-shaped mass in the abdomen. Bloodwork showed hypokalaemic metabolic alkalosis. Abdominal ultrasound and radiograph was significant for portal venous gas and did not meet radiographic criteria for pyloric stenosis. He underwent upper endoscopy, which showed a narrowed, hypertrophic pylorus. The child underwent pyloromyotomy with resolution of his emesis. Hepatic portal venous gas (HPVG) is very rare and can be seen in the setting of hypertrophic pyloric stenosis. It is believed that an increase in intraluminal dilation and pressure subsequently moves gas from the intestinal mucosa venous system and lymphatics into the portal veins. The presence of HPVG in a well-appearing patient can be benign and should not prompt further testing nor delay treatment.

Pericecal hernia: a rare form of internal hernias.

We report a rare and interesting case of a pericecal hernia. A 34-year-old male presented to the emergency department with severe periumbilical pain, emesis and a prior syncopal episode. He noted a 3-month history of intermittent, colicky periumbilical pain. His abdominal examination demonstrated a palpable mass in the right lower quadrant, involuntary guarding and rebound tenderness. CT demonstrated dilated small-bowel loops and findings suggestive of ischemia. The patient was immediately taken to the operating room where a diagnosis of pericecal hernia was made. The patient underwent a reduction of the hernia and a repair of the mesenteric defect.