DNA Methylation Signature of Synchronous Endometrioid Endometrial and Ovarian Carcinomas.

Next-generation sequencing (NGS) studies have demonstrated that co-occurring sporadic endometrioid endometrial carcinoma (EEC) and endometrioid ovarian carcinoma (EOC) are clonally related, suggesting that they originate from a single primary tumor. Despite clonality, synchronous EEC and EOC when diagnosed at early stage behave indolently, similar to isolated primary EEC or isolated primary EOC. In the present study, we compared the DNA methylation signatures of co-occurring EEC and EOC with those of isolated primary EEC and isolated primary EOC. We also performed targeted NGS to assess the clonal relatedness of 7 co-occurring EEC and EOC (4 synchronous EEC and EOC and 3 metastatic EEC based on pathologic criteria). NGS confirmed a clonal relationship in all co-occurring EEC and EOC. DNA methylation profiling showed distinct epigenetic signatures of isolated primary EEC and isolated primary EOC. Endometrial tumors from co-occurring EEC and EOC clustered with isolated primary EEC while their ovarian counterparts clustered with isolated primary EOC. Three co-occurring EEC and EOC cases with peritoneal lesions showed a closer epigenetic signature and copy number variation profile between the peritoneal lesion and EOC than EEC. In conclusion, synchronous sporadic EEC and EOC are clonally related but demonstrate a shift in DNA methylation signatures between ovarian and endometrial tumors as well as epigenetic overlap between ovarian and peritoneal tumors. Our results suggest that tumor microenvironment in the ovary may play a role in epigenetic modulation of metastatic EEC.

The association of cemiplimab plus sonidegib for synchronous cutaneous squamous cell carcinoma and basal cell carcinoma of the head and neck: Two case reports.

Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) are the most frequent cancers in humans, with cumulative ultraviolet radiation exposure, aging, and immunodepression as the main risk factors. In most cases, these malignancies arise in the head and neck area, and they can be treated with locoregional therapies. A minority of cases require systemic therapy. Currently, Sonic Hedgehog inhibitors (i.e., vismodegib and sonidegib) have been approved for advanced BCC, while the PD-1 checkpoint inhibitor cemiplimab has been approved as a first-line treatment for cSCC and as a second-line treatment for BCC. Nevertheless, there is a clinical need for an effective and safe systemic therapies for advanced synchronous (syn) BCC/cSCC not amenable to local treatments. International guidelines do not provide specific recommendations for patients affected by this condition, and no case reports on the full-dose association of these medications have been previously reported. Here, we present the cases of two elderly patients affected by synBCC/cSCC of the head and neck, who received combined therapy with cemiplimab and sonidegib at full dose and standard schedule, achieving remarkable clinical benefit and long-term responses, without major adverse events. The instance of a feasible treatment for patients with advanced synBCC/cSCC will become increasingly frequent with the advancement of life expectancy in the global population, and the synergistic activity of targeted therapies and immunotherapy-administered either in association or sequentially-deserves to be further explored.

The prognosis of stage IA synchronous endometrial endometrioid and ovarian carcinomas.

INTRODUCTION: Little is known about the prevalence and prognosis of synchronous endometrial and ovarian carcinomas. This report explores the survival outcomes of synchronous stage IA endometrioid endometrial and stage IA ovarian carcinomas in a retrospective cohort study. METHODS: All cases of pathological confirmed synchronous stage IA endometrial endometrioid and ovarian carcinomas from June 1, 2010, to June 1, 2017, in a teaching hospital were reviewed. Patients were followed up to February 1, 2019. Survival outcomes were compared between patients with and without synchronous carcinomas. RESULTS: In total, 841 cases with confirmed FIGO stage IA endometrioid endometrial carcinomas were included in the study; 33 patients (3.9%) had synchronous stage IA ovarian carcinomas, including 27 (81.8%) and 6 (18.2%) cases of endometrioid and mixed endometrioid/clear cell subtypes, respectively. After a median follow-up time of 56.8 months, 829 patients (97.9%) had definitive survival outcomes. Synchronous ovarian carcinomas had no impact on disease-free, overall or cancer-specific overall survival in univariate and multivariate analyses. CONCLUSION: In these patients with stage IA endometrioid endometrial carcinoma, the genuine incidence of synchronous stage IA ovarian carcinoma was very low, and synchronous carcinoma had no significant effects on survival outcomes.

Risk-based stratification of carcinomas concurrently involving the endometrium and ovary.

OBJECTIVE: Determining whether carcinomas concurrently involving endometrium and ovary are independent primary tumors (IPTs) or endometrial carcinomas with ovarian metastases (at least stage IIIA endometrial cancers, IIIA-EC) using clinicopathologic criteria is often challenging. Recent genomic studies showed that most such tumors are clonally related. We sought to identify clinicopathologic features associated with clinical outcomes, and to separate women with these tumors into clinically low-risk and high-risk groups. METHODS: We reviewed clinical and pathologic data from 74 women who, between 1993 and 2014, underwent primary surgery for endometrial cancer and had concurrent ovarian involvement. RESULTS: The endometrial carcinomas were endometrioid (EECs, n = 41) or non-endometrioid (ENECs, n = 33). Nineteen (26%) cases were originally classified as IPTs using clinicopathologic criteria. Multivariate analysis revealed that lymph node involvement (hazard ratio (HR) = 2.38, 95% CI 1.13-5.02, p = 0.023) and non-endometrioid endometrial tumor histology (HR = 6.27, 95% CI 2.6-15.13, p < 0.001) were associated with poorer progression-free survival (PFS). Multivariate analysis of 65 women with known lymph node status revealed two prognostically distinct groups: a high-risk group comprising ENECs with ≥50% myometrial invasion irrespective of lymph node status (n = 21; median PFS 12.7 months, 95% CI, 9.24-19.8); and a low-risk group consisting of all EECs, as well as lymph node-negative ENECs with <50% myometrial invasion (n = 44, median PFS not reached). The risk-based classification was superior to the original classification of endometrial cancers as IPTs vs. IIIA-EC for predicting PFS (log-rank test, p < 0.001 vs. p = 0.07). CONCLUSION: Our proposed risk-based stratification enables categorization of women with concurrent endometrial and ovarian tumors according to their likely clinical outcomes.

Synchronous Pancreatic Ductal Adenocarcinoma and Hepatocellular Carcinoma: Report of a Case and Review of the Literature.

Two or more histologically distinct malignancies diagnosed during the same hospital admission are uncommon, but they do exist. Cases with synchronous primary pancreatic ductal adenocarcinoma and hepatocellular carcinoma are rarely seen. This is a case report of a 56 years old Caucasian female with the chief complaint of jaundice over a duration of 10 days. CT imaging findings revealed a 3.5 cm ill-defined pancreatic head mass and a 1.5 cm liver mass in the segment 5. EUS-FNA cytology showed pancreatic head ductal adenocarcinoma (PDAC). Liver biopsy revealed a well differentiated hepatocellular carcinoma (HCC). The patient underwent a pancreaticoduodenectomy and the pathology revealed a pancreatic ductal adenocarcinoma extending into peripancreatic soft tissue, portal vein and vascular groove with perineural invasion. This is a unique and challenging case with the coexistence of a primary PDAC and a primary HCC. To the best of our knowledge, this is the first documented case of synchronous PDAC and HCC in the English literature. The diagnosis and treatment of the two entities are discussed.

Minimally invasive resection of synchronous thoracic esophageal and gastric carcinomas followed by reconstruction: a case report.

We report on a case of synchronous carcinomas of the esophagus and stomach. A 68-year-old man was referred to our hospital for an abnormality found during his medical examination. Further evaluation revealed squamous cell carcinoma in the thoracic lower esophagus and gastric adenocarcinoma located in the middle third of the stomach. Thoracoscopic esophagectomy in the prone position (TSEP), laparoscopic total gastrectomy (LTG) with three-field lymph node dissection, and laparoscopically assisted colon reconstruction (LACR) were performed. The patient did not have any major postoperative complications. His pathological examination revealed no metastases in 56 harvested lymph nodes and no residual tumor. He was followed up for 30 months without recurrence. To our knowledge, this is the first report of esophageal and gastric synchronous carcinomas that were successfully treated with a combination of TSEP, LTG, and LACR. These operations may be a feasible and appropriate treatment for this disease.

Coexisting primary central nervous system non-Hodgkin's lymphoma and colorectal adenocarcinoma: A case report.

A 61-year-old female presented with night sweats following a resection for non-Hodgkin's lymphoma of splenium corporis callosi. A positron emission tomography-computed tomography scan demonstrated that original lymphoma activity remained. A new ascending colon mass was identified simultaneously, which was diagnosed as an adenocarcinoma following the surgery. To the best of our knowledge, this is the first case to report a coexistence of primary central nervous system non-Hodgkin's lymphoma and colorectal adenocarcinoma. The case poses a difficult clinical challenge.

Synchronous oral squamous cell carcinomas with unusual histopathological feature.

Patients with head and neck carcinomas have high incidence (2-3% per year) of second primary lesions. Although "field cancerization" was first described in oral squamous cell carcinomas (OSCCs), only few studies have been concentrated on multifocal primary squamous cell carcinomas in the oral cavity. Synchronous carcinomas are defined as second neoplasms at the same time or within 6 months period of primary lesions. After this period, they are considered as metachronous neoplasms. Tumors composed exclusively or in large part of clear cells are rare in salivary glands, jaws and oral mucosa. OSCCs composed of clear cells or clear cell variant are not documented in the English literature. We present an unusual case of synchronous OSCCs composed predominantly of clear cells.

Endometrial Cancer: Comparison of Patients with Synchronous Primary Carcinoma of the Endometrium and Ovary vs. Endometrial Carcinoma with Ovarian Metastases.

Purpose: The aim of our study was to investigate the rate of secondary carcinomas in patients with endometrial carcinoma (EC). In particular, we wanted to describe the subset of patients with endometrial and simultaneous ovarian carcinoma (OC), including outcomes. The study also compared patients with EC and ovarian metastasis with patients with EC and simultaneous OC. Patients and Methods: Data from 251 patients with primary endometrial carcinoma who underwent surgery in the years 2005-2009 at the Department of Obstetrics and Gynaecology, University of Tübingen, were analysed retrospectively. Results: A total of 28 patients (11.1 %) had a secondary carcinoma: 18 patients (7.1 %) had OC; 9 (3.5 %) patients had a history of breast cancer, and one patient (0.4 %) respectively had simultaneous carcinoma of the vulva or bladder. 14 patients (5.5 %) had advanced stage EC with ovarian metastasis or, in one case, metastasis to the ovarian tube. Patients with ovarian metastasis had a mean age of 71.2 ± 9.2 years at primary diagnosis, making them significantly older compared to patients with EC and simultaneous OC (55.3 ± 11.8 years, p < 0.001). Moreover, patients with ovarian metastasis significantly more often had EC with a higher tumour grade (grade 1: 0, grade 2: 21.4 %, grade 3: 78.6 %) compared to patients with simultaneous EC and OC (grade 1: 11.1 %, grade 2: 77.8 %, grade 3: 11.1 %; p < 0.001). Conclusion: Almost one in 10 patients with EC had a secondary carcinoma. The most common secondary carcinoma was OC followed by breast cancer. This should be taken into account in the diagnosis and therapy of patients with EC. Patients with simultaneous EC and OC were significantly younger than patients with EC and ovarian metastasis. In addition, their tumour had better prognostic features: thus, the tumour grade of the EC was significantly lower. Overall, the prognosis for patients with synchronous EC and OC is better than that for patients with EC and ovarian metastasis.

Synchronous and metachronous adenocarcinomas of the large intestine.

BACKGROUND AND AIM: The synchronous and consecutive (metachronous) development of two or more primary adenocarcinomas accounts for 3 to 5% of cases of colorectal cancer. Aim of this study is to review our experience in the management of patients with synchronous and metachronous lesions, and reach conclusions regarding their optimal diagnosis, treatment and follow-up. PATIENTS AND METHODS: Between 1987 and 2004, 12 patients (seven men and five women, mean age 67.5 years, range 47-83 years) with synchronous (three patients) and metachronous (nine patients) lesions were treated, comprising 4.3% of all patients submitted to surgery for colorectal cancer. The diagnosis lag for metachronous lesions ranged from 1.5 to 14 years. All three patients with synchronous cancers had two lesions. RESULTS: Staging colonoscopy and abdominal CT was conducted in 10 patients while the remaining two underwent only abdominal CT due to their critical condition at presentation. Surgery had curative intent in 10 patients and palliative in two. The mean postoperative hospital stay was 21 days (10-49 days). The postoperative mortality was zero. Patients survival after curative procedures was 80% for the first year, 60% for the third and 50% for the fifth year. After palliative surgery, survival was 50% for the first year, and zero for the third. CONCLUSIONS: Patients with colorectal cancer must be followed up regularly after surgery. Follow up aims at early diagnosis and treatment of metachronous lesions that can appear many years after diagnosis of the primary lesion. Preoperative colonoscopy is an invaluable diagnostic (biopsy) and staging (exclusion of synchronous lesions, localization of the primary) modality, dictating the surgical approach. Additionally, it contributes to cancer prevention allowing the discovery and removal of small polyps before their transformation.