Detection and Outcome of Endocervical Atypia in Cytology in Primary HPV Screening Programme

Most endocervical adenocarcinomas (EAC) are associated with high-risk HPV (hrHPV) infection, with HPV genotypes 16, 18 and 45 accounting for >90% of the cases. Among endocervical glandular lesions, screening with hrHPV test has previously shown to predict the outcome better than cytology, although around one-fifth of the EAC remain negative both in hrHPV testing and cytology. The study consists of two consecutive HPV-primary screening rounds, conducted in 2012–2015 and 2017–2020. Of the 87 women aged 35 to 60 years of age diagnosed with Atypical endocervical cells, NOS or Atypical endocervical cells, favor neoplastic cytology during the first screening round, 63 (72.4%) were hrHPV positive and 24 (27.6%) were hrHPV negative. Among hrHPV positive patients, three EAC, two adenocarcinomas in situ (AIS), one AIS + high-grade intraepithelial lesion (HSIL) and 13 HSIL were found. Of the histologically verified lesions, 68.4% (13/19) were purely of squamous origin. All the EAC and AIS were HPV16 or HPV 18 positive. No high-grade histological lesions were found among the hrHPV negative patients with cytological glandular atypia. A later database search revealed one HPV-negative, gastric-type mucinous EAC that was missed by the HPV primary screening.

Prognostic Factors and Clinical Characteristics of Duodenal Adenocarcinoma With Survival: A Retrospective Study

BackgroundTo evaluate the clinical risk factors that influence the overall survival in patients with duodenal adenocarcinoma (DA) after tumor resection.MethodsThis study retrospectively analyzed 188 patients who underwent tumor resection for DA between January 2005 and June 2020 at Xiangyang Central Hospital.ResultsThe median survival of the patients who underwent resectional operation was 54 months, longer than of those who underwent palliative surgery (20.8 months) (2,916.17; 95% CI, 916.3−9,280.5; p < 0.001). Survival of non-ampullary duodenal carcinoma patients (50.3 months; 95% CI, 39.7−61.8) was similar to that of ampullary duodenal carcinoma patients (59.3 months; 95% CI, 38.6−66.7) but was significantly better than that of papillary adenocarcinoma patients (38.9 months; 95% CI, 29.8−54.8; p = 0.386). Those with intestinal-type ductal adenocarcinomas had a longer median overall survival than those with the gastric type (61.8 vs. 46.7 months; p < 0.01) or pancreatic type (32.2 months; p < 0.001). Clinical DA samples had significantly diverse expressions of ATG12, IRS2, and IGF2. Higher expressions of the ATG12 and IRS2 proteins were significantly correlated with worse survival. Multivariate Cox regression analysis revealed that lymph node metastasis (hazard ratio (HR), 6.44; 95% CI, 3.68−11.27; p < 0.0001), margin status (HR, 4.94; 95% CI, 2.85−8.54; p < 0.0001), and high expression of ATG12 (HR, 1.89; 95% CI, 1.17−3.06; p = 0.0099) were independent prognostic factors negatively associated with survival in patients undergoing curative resection. There was no survival difference between the groups with ampullary, non-ampullary, and papillary adenocarcinomas treated with adjuvant chemotherapy (p = 0.973).ConclusionGastric/pancreatic type, high expression of ATG12, lymph node metastases, and margin status were negative prognosticators of survival in patients with DAs than in those with tumor anatomical location. Curative resection is the best treatment option for appropriate patients.

Gastric-type adenocarcinoma of the cervix in patients with Peutz-Jeghers syndrome: a systematic review of the literature with proposed screening guidelines

ObjectivesTo perform a systematic review of gastric-type adenocarcinoma of the cervix and lobular endocervical glandular hyperplasia (a possible precursor lesion) in Peutz-Jeghers syndrome, and to analyze data from the literature, along with our institutional experience, to determine recommendations for screening and detection.MethodsA comprehensive literature searc and retrospective search of pathology records at our institutio were conducted. Articles were screened by two independent reviewers. Case reports/series on lobular endocervical glandular hyperplasia/gastric-type adenocarcinoma of the cervix in Peutz-Jeghers syndrome were included. Demographic, clinical, and radiologic information was collected.ResultsA total of 1564 publications were reviewed; 38 met the inclusion criteria. Forty-nine were included in the analysis (43 from the literature, 6 from our institution). Forty-three reported on gastric-type adenocarcinoma alone, 4 on lobular endocervical glandular hyperplasia alone, and 2 on concurrent lobular endocervical glandular hyperplasia/gastric-type adenocarcinoma. Median age at diagnosis was 17 (range, 4–52) for patients with lobular endocervical glandular hyperplasia alone and 35 (range, 15–72) for those with gastric-type adenocarcinoma. The most common presenting symptoms were abdominal/pelvic pain and vaginal bleeding/discharge. Imaging was reported for 27 patients; 24 (89%) had abnormal cervical features. Papanicolaou (Pap) smear prior to diagnosis was reported for 12 patients; 6 (50%) had normal cytology, 4 (33%) atypical glandular cells, and 2 (17%) atypical cells not otherwise specified. Patients with gastric-type adenocarcinoma (n=45) were treated with surgery alone (n=16), surgery/chemotherapy/radiation (n=11), surgery/chemotherapy (n=9), surgery/radiation (n=5), or radiation/chemotherapy (n=4). Twelve (27%) of 45 patients recurred; median progression-free survival was 10 months (range, 1–148). Twenty patients (44%) died; median overall survival was 26 months (range, 2–156). Thirteen patients (27%) were alive with no evidence of disease.ConclusionsGastric-type adenocarcinoma in Peutz-Jeghers syndrome is associated with poor outcomes and short progression-free and overall survival. Screening recommendations, including pathognomonic symptom review and physical examination, with a low threshold for imaging and biopsy, may detect precursor lesions and early-stage gastric-type adenocarcinoma, leading to better outcomes in this high-risk population.PROSPERO registration numberCRD42019118151

Pancreatic medullary carcinoma developed on a pancreatic intraductal papillary mucinous neoplasm with loss of MSH2 and MSH6 expression: a case report

Background Pancreatic medullary carcinoma (PMC) is a rare pancreatic tumor, usually showing the presence of microsatellite instability, mostly MLH1 silencing, and a wild-type KRAS mutation status. We report here a PMC arising from a Pancreatic Intraductal Papillary Mucinous Neoplasm (IPMN), both having KRAS and TP53 mutations. Case presentation We report the case of a 73-year-old woman presenting with right iliac fossa pain. MRI revealed a 16 mm diameter mass in the pancreas, leading to a pancreatic duct stricture and upstream a dilatation of the distal pancreatic duct of Wirsung. A fine needle aspiration was performed, and pathology analysis revealed malignant glandular cells. The patient underwent distal pancreatectomy. Gross examination revealed an12 mm indurated white lesion, adjacent to a cystic lesion extending into the rest of the pancreatic body. Microscopically, the cystic area represented a mixed (gastric-type and pancreatobiliary-type) IPMN, involving the main and secondary pancreatic ducts with low-grade and high-grade dysplasia. In the periphery of this IPMN, a 14mm associated invasive carcinoma was observed, characterized by focal gland formation and by poorly differentiated cells with a syncytial appearance, associated with a dense lymphoplasmocytic and neutrophilic infiltrate. Immunohistochemical analyses showed loss of MSH2 and MSH6 expression. Microsatellite instability was confirmed by molecular test. Molecular analysis was performed both on the invasive carcinoma and on the high-grade dysplasia IPMN, revealing the same mutation profile with KRAS and TP53 mutations. The proposed diagnosis was mixed IPMN with associated invasive medullary carcinoma that presented loss of MSH2 and MSH6 expression. Conclusions The present case reports for the first time, at the best of our knowledge, the coexistence of IPMN lesions and PMC, both having the same molecular alterations. It also describes the second case of PMC with microsatellite instability, MSH2 and MSH6 silenced.

Recurrent intraductal papillary neoplasm of the bile duct due to intraductal dissemination: a case report and literature review

Background Intraductal papillary neoplasm of the bile duct (IPNB) is a subtype of biliary tumor. The 5-year survival rate of patients with IPNB who underwent curative resection is 81%. However, IPNB is known to often recur in other parts of the bile duct. Nevertheless, its mechanism remains poorly understood. Herein, we report the case of a patient with recurrent IPNB, which was considered to be attributed to intraductal dissemination in the common bile duct at 12 months after curative resection. We also made a review of the existing literature. Case presentation A 69-year-old man was referred to our hospital for the evaluation and dilation of an intrahepatic bile duct (IHBD) mass. Computed tomography (CT) findings confirmed a mass in the left hepatic duct. Left trisectionectomy, extrahepatic bile duct resection with biliary reconstruction, and regional lymph node dissection were performed. Intraoperative examination of the resection margin at the common bile duct and posterior segmental branch of the hepatic duct was negative for the presence of malignant cells. Histologically, the tumor showed intraductal papillary growth of the mucinous epithelium and was diagnosed as non-invasive IPNB. It had a papillary structure with atypical epithelial cells lined up along the neoplastic fibrovascular stalks. Immunohistochemically, this was as a gastric-type lesion. At 12 postoperative months, CT revealed a 1.5-cm mass in the lower remnant common bile duct. We performed subtotal stomach-preserving pancreaticoduodenectomy. The tumor exhibited papillary growth and was microscopically and immunohistochemically similar to the first tumor. At approximately 16 months after the patient’s second discharge, CT showed an abdominal mass at the superior mesenteric plexus, which was diagnosed as recurrent IPNB. Chemotherapy is ongoing, and the patient is still alive. In this case, as described in many previous reports, IPNB recurred below the primary lesion in the bile duct. Conclusion Based on our review of previous reports on IPNB recurrence, intraductal dissemination was considered one of the mechanisms underlying recurrence after multicentric development. Considering the high frequency and oncological conversion of recurrence in IPNB, regular follow-up examination is essential to achieve better prognosis in patients with recurrent IPNB.

Clinicopathological features and outcomes in gastric-type of HPV-independent endocervical adenocarcinomas

Background We aimed to analyze the clinicopathological features and outcomes of patients with gastric-type of HPV-independent endocervical adenocarcinoma (GAS HPVI ECA), and compare them with non-GAS HPVI ECA cases. Methods Thirty-eight GASs [including 17 minimal deviation adenocarcinoma (MDA), 21 non-MDA GAS] and 17 non-GAS HPVI ECAs were studied. Data of clinical features, pathological characteristics, treatment, and outcomes were evaluated. Results The median age of patients with GAS and non-GAS HPVI ECA was 46 and 48 years, respectively (p = 0.93). Compared with non-GAS HPVI ECAs, GAS had more common complains of vaginal watery discharge (p = 0.04). GAS cases were also associated with higher clinical stage (p = 0.036), more common in deeper cervical stromal invasion (p = 0.002) and lymphoavascular invasion (p = 0.044). GAS was associated with worse median progression-free survival (PFS) (p = 0.02) and median overall survival (OS) (p = 0.03) over patients with non-GAS HPVI ECAs. MDA had similar clinical and pathological features and prognosis compared with non-MDA GAS. Of note, serum CA19–9 levels were significantly higher in GAS than that in non-GAS HPVI ECA cases. Conclusions GAS cases were more likely to have high risk pathological factors and poorer PFS and OS compared with non-GAS HPVI ECAs. Serum CA19–9 may be helpful for diagnosis and screening in patients with GAS.