Subtype Of Mucinous Adenocarcinoma Research Articles

Propensity-Score Matched Analysis of Survival Outcomes of Adjuvant Therapy in Stage II-III Signet-Ring Cell Carcinoma of the Colon

BackgroundColonic signet ring cell carcinoma (SRCC) is a mucinous adenocarcinoma subtype often associated with poor prognosis. This study assessed the survival benefits of adjuvant therapy after curative resection of stage II-III colonic SRCC. MethodsThis was a retrospective analysis of outcomes of adjuvant therapy in colonic SRCC using National Cancer Database (2010-2019) data. Patients who received adjuvant therapy were matched to those who did not use the nearest neighbor propensity-score matching. The primary outcome was 5-year overall survival (OS). ResultsThe unmatched cohort included 3530 patients. Patients who received adjuvant therapy were significantly younger, more often male, and more often had Charlson scores 0-1, left-sided cancers, stage III disease, lymphovascular invasion, and perineural invasion. The matched cohort included 958 patients (53.6% female); 479 received adjuvant therapy and 479 did not. Adjuvant therapy was associated with longer mean OS (39.9 vs. 29.2 months; P < .001). Survival benefit of adjuvant therapy was evident in stage III disease (37.5 vs. 24.7 months; P < .001), right-sided colon cancer (40.2 vs. 27.7 months; P < .001), and transverse colon cancer (40.6 vs. 31.1 months; P = .002), but not stage II disease (52.1 vs. 53.1 months; P = .694) or left-sided colon cancer (35.8 vs. 32.6 months; P = .417). Independent predictors of improved OS were adjuvant therapy (HR: 0.539; P < .001), laparoscopic surgery (HR: 0.829; P = .001), robotic-assisted surgery (HR: 0.63; P = .007), and number of harvested lymph nodes (HR: 0.976; P < .001). ConclusionsAdjuvant therapy was associated with improved OS in stage III, right-sided, and transverse colon SRCC. The survival benefit of adjuvant therapy in stage II and left-sided colon SRCC was limited.

Molecular detection of mononucleotide biomarkers of microsatellite instability in sporadic colorectal carcinoma patients with clinicopathological correlation

Objectives: To identify the frequency and types of microsatellite instability among a group of sporadic CRC patients and to correlate the findings with clinicopathological characteristics.&#x0D; Methods: During an 8-month period, all patients with sporadic CRC who attended to two teaching hospitals in Baghdad, Iraq were recruited to this cross-sectional study regardless of age, sex, ethnicity, or tumor characteristics. Demographic, clinical, and histopathological features were recorded. DNA was extracted from FFPE-blocks of the resected tumors and normal tissues. PCR amplification of five microsatellite mononucleotide repeat loci (BAT25, BAT26, NR-21, NR-24, and MONO-27) and 2 pentanucleotide repeat control markers (Penta C and Penta D) was performed to determine the MSI status. Capillary electrophoresis and Genetic Analyzer 3500 (Applied Biosystem, Japan) were used to separate and examine the products. Data were analyzed by Genescan software (Promega, USA). Instability of two or more loci is considered MSI-H.&#x0D; Result: In this study, ages of the 45 recruited patients ranged between 20-80 years, with a mean±SD of 55±12.3 years; of them, 31(68.9%) were ≥50 years; 25 (55.6%) were males. Rectal bleeding was the most frequent presenting feature [22 (48.9%)] patients; 23 (51.1%) of CRCs were located at recto-sigmoid region, 29 (64.4%) were T3 tumors, 34(75.5%) were non-mucinous adenocarcinoma, 39(86.7%) were moderately differentiated, 17 (37.8%) patients had stage III tumors; and 25 (55.5%) had lymphovascular invasion. MSI-H was seen in 5/45 (11.1%) patients; 3(60%) of them were ≥50 years, 4(80%) were males, 3(60%) were smokers, 2 (40%) presented with intestinal obstruction and altered bowel habits each; 4(80%) had T3 tumors, 3(60%) had mucinous adenocarcinomas [p=0.004], 2(40%) had stage II tumor and stage III each.&#x0D; Conclusion: The frequency of MSI-H among the recruited patients with CRC was 5/45 (11.1%) and it was significantly associated with mucinous adenocarcinoma subtype. NR-24 and NR-21 were the most prevalent instable markers.

NKX3.1 Expression in Salivary Gland "Intraductal" Papillary Mucinous Neoplasm: A Low-Grade Subtype of Salivary Gland Mucinous Adenocarcinoma.

Salivary gland intraductal papillary mucinous neoplasm (SG IPMN) is a recently proposed entity characterized by a papillary-cystic proliferation of mucin-producing cells. Because of overlapping histologic features and a clonal AKT1 p.E17K variant, SG IPMN has been presumed to be a precursor or a low-grade subtype of mucinous adenocarcinoma. NKX3.1 is a tumor suppressor gene located on chromosome 8p and is a known immunohistochemical marker of prostate epithelium and mucinous acinar cells of the intraoral salivary glands. We retrieved 12 SG IPMN cases, and performed histologic and genetic analysis. Given the association of SG IPMN with mucinous acinar cells, we also investigated the performance of NKX3.1 as a marker of this tumor entity. Diffuse and strong NKX3.1 expression was observed in all SG IPMN cases (12/12, 100%) as well as in normal mucinous acinar cells. In contrast, mucoepidermoid carcinoma and pancreatic IPMN cases as well as normal serous acinar cells were negative for NKX3.1. Genetically, 11 of 12 cases (92%) harbored an AKT1 p.E17K variant. A novel PTEN frameshift deletion (p.G36Dfs*18) was detected in the other single case. At least one of the histologic features implying malignant tumors, such as severe cellular atypia, brisk mitotic activity, high Ki-67 proliferating index, lymphovascular invasion, and lymph node metastasis, was detected in 6 SG IPMN cases (50%). The findings suggest that SG IPMN is a low-grade subtype of mucinous adenocarcinoma which may be derived from mucinous acinar cells of the minor salivary gland.

Comparative analysis of clinical, treatment, and survival characteristics of signet ring cell and adenocarcinoma of esophagus.

Signet ring cell carcinoma (SRC) is a rare pathological subtype of mucinous adenocarcinoma (AC). Clinical features, prognosis, and especially treatment methods between SRC and AC of the esophagus remain controversial. Thus, we conducted this study to explore the differences in clinicopathological characteristics and treatment modalities between SRC and AC of the esophagus. A retrospective cohort study based on the Surveillance, Epidemiology, and End Results (SEER) program database was conducted. Patients diagnosed with SRC or AC not otherwise specified (NOS) were selected between 2004 and 2018. We investigated the prognosis of SRC and AC in terms of overall survival (OS). A subgroup analysis was performed according to the stage and different treatment methods. A total of 24,987 patients were enrolled, including 1,147 with SRC and 23,840 with AC. In the multivariate Cox analysis of the whole cohort, SRC, tumor site, differentiation, metastases, American Joint Committee on Cancer (AJCC) 6th edition staging, treatment, tumor size, lymph nodes examined, and positive lymph nodes were independent risk factors. The results of the subgroup analysis showed that surgery alone was associated with better OS for AC at the early stage, but was not significantly different for SRC (P=0.896). Surgery plus adjuvant therapy was the best treatment for SRC and AC at the late stage. In the multivariate Cox analysis, the treatment of surgery plus adjuvant therapy had a tendency towards better OS at the early stage [hazard ratio (HR): 0.64, 95% confidence interval (CI): 0.39-1.1, P=0.08]. SRC is an independent risk factor, with a higher grade of differentiation, later stage, larger tumor size, more positive lymph nodes, and poorer prognosis compared with AC. Surgery plus adjuvant therapy seems to be useful for SRC at the early stage, but further research is needed.

Caractéristiques épidémiologiques et histopathologiques de 1280 cancers du col utérin à Kinshasa

ObjectiveDue to the lack of both cancer registry and large scale cervical screening in most african countries, only theoretical studies are available. The objective of our work was to provide epidemiological and histopathological characteristics of cervical cancer based on concrete observations. MethodsThis study was carried out on all cancers (n=5801) collected in the last 10 years from 5 pathology laboratories of Kinshasa; the histologic slides of the cervical cancers (n=1280) were reviewed by at least two pathologists and classified according to the 2014 OMS classification. ResultsThe cervical cancers accounted for 22% of all cancers and 40,4% of breast and gynecological cancers. The cervical cancer was the most common among women aged 49-58. Squamous cell carcinomas were the most observed type (73,2%) followed by adenocarcinomas (18,4%) and adenosquamous carcinomas (8,4%). Keratinized (47,2%) and non keratinized squamous carcinoma (20,8%) were the most frequent subtypes among squamous carcinomas and the usual adenocarcinoma among adenocarcinomas (9,6%). In the mucinous adenocarcinoma subtype, only the signet ring cells (1,3%) variant was found. Among cervical cancers, 69% were grade I, 20% grade II and 11% grade III. ConclusionOur study provides a concrete database of epidemiological and histopathological cervical cancer particularities in Kinshasa, useful to initiate a cancer register, as well as cervical screening and HPV vaccine campaigns.

Identification of Potential Biomarkers and Biological Pathways for Poor Clinical Outcome in Mucinous Colorectal Adenocarcinoma.

Simple SummaryPatients with mucinous adenocarcinoma (MAC) have been considered to have a faster disease progression than patients with traditional adenocarcinoma (TAC) in colorectal cancer (CRC). However, to date, the roles of MAC in long-term survival remain controversial due to a small sample size and the nature of its relatively rare occurrence, although it potentially represents entities with different aggressiveness and prognoses. Here, using large-scale population data, we found that the patients with the MAC subtype had a significantly worse overall survival rate and a tendency of worse disease-specific survival rate in stage II compared with the patients with the TAC subtype. Furthermore, key gene signatures were identified using the established predictive models for the disease-specific survival of stage II mucinous CRC.Colorectal cancer (CRC) comprises several histological subtypes, but the influences of the histological subtypes on prognosis remains unclear. We sought to evaluate the prognosis of mucinous adenocarcinoma (MAC), compared to that of traditional adenocarcinoma (TAC). This study used the data of patients diagnosed with CRC between 2004 and 2016, as obtained from the Surveillance, Epidemiology, and End Results database. We established a predictive model for disease-specific survival using conditional survival forest, model, non-linear Cox proportional hazards, and neural multi-task logistic regression model and identified the gene signatures for predicting poor prognosis based on the arrayexpress datasets. In total, 9096 (42.1%) patients with MAC and 12,490 (58.9%) patients with TAC were included. Those with the MAC subtype were more likely to have a poorer overall survival rate compared to those with the TAC subtype in stage II CRC (p = 0.002). The eight major genes including RPS18, RPL30, NME2, USP33, GAB2, RPS3A, RPS25, and CEP57 were found in the interacting network pathway. MAC was found to have a poorer prognosis compared to TAC, especially in Stage II CRC. In addition, our findings suggest that identifying potential biomarkers and biological pathways can be useful in CRC prognosis.

Cervical Adenoma Malignum in Third Trimester Pregnancy

Teaching Point: Adenoma malignum is a rare, non-HPV associated subtype of mucinous adenocarcinoma of the cervix, of which we present an exceptional case that was discovered during the third trimester of pregnancy.

RAS/RAF mutations and their associations with epigenetic alterations for distinct pathways in Vietnamese colorectal cancer

KRAS, NRAS, and BRAF are potential tumor-driven genes that are involved in the RAS/RAF/MAPK signaling pathway. RAS/RAF mutations importantly contribute to colorectal tumorigenesis since they remain the activated status of downstream pathways without regulation of the upstream EGFR signal. However, it has not been unclear how epigenetic alterations involved in colorectal tumorigenesis mediated by KRAS, NRAS, or BRAF mutations. Therefore, in this study, we investigated the frequency and distribution of KRAS/NRAS/BRAF mutations in Vietnamese colorectal cancer (CRC) and explored the relationship between genetic and epigenetic abnormalities in 156 tumors of CRC. Somatic mutations of KRAS (exon 2, codon 12/13; exon 3, codon 61), NRAS (exon 2, codon 12/13; exon 3, codon 61), and BRAF (exon 15, codon 600) was determined by Cobas® KRAS Mutation Test, Therascreen NRAS Pyro Kit and Cobas® 4800 BRAF V600 Mutation Test, respectively. Methylation status of BRCA1, MLH1, MGMT, p16, RASSF1A, and APC was detected by methylation-specific PCR. Distribution of each abnormality in clinicopathological features was also analyzed. Results showed the mutation rates of KRAS, NRAS, and BRAF were 41.0 %, 9.6 %, 8.3 % respectively, while the methylation rates of BRCA1, MLH1, MGMT, p16, RASSF1A, and APC were 16.7 %, 16.7 %, 32.7 %, 30.1 %, 30.1 %, and 37.2 % respectively. The distribution of KRAS mutation was mutually exclusive against that of NRAS (p < 0.001) and BRAF (p < 0.001) mutations in CRC. RAS/RAF mutations were more common in adenocarcinoma subtype (p = 0.020), whereas RASSF1A methylation was more frequent in mucinous adenocarcinoma subtype (p = 0.007). In addition, the frequency of having KRAS mutations was significantly higher in MGMT (p = 0.035) or RASSF1A (p = 0.043) methylated cases than in those without methylation. BRAF mutations were positively associated with MLH1 hypermethylation (p = 0.028) but were inversely associated with APC hypermethylation (p = 0.032). Overall, our results show specific interactions of genetic and epigenetic alterations and suggest the presence of independent oncogenic pathways in tumorigenesis of CRC.

SYSTEMIC CHEMOTHERAPY IN APPENDICEAL ADENOCARCINOMAS WITH PERITONEAL METASTASES. IS IT WORTH IT?

Introduction: The role of systemic chemotherapy (SC) in the management of metastatic appendiceal adenocarcinomas is not defined.Methods: We perform an observational study of patients treated of peritoneal metastases from appendiceal neoplasm between June 2004 and December 2017. They were referred to our hospital for CRS HIPEC. Systemic Chemotherapy regimens were decided by the referring oncologist. We analyze PCI, CC, and use of SC. Overall survival and progression free survival were compared attending to histologic subtype (high- and low-grade adenocarcinomas) and the use of SC.Results: 60 patients were included, 26 were male, median age 63 years (26-81). Median follow-up of 38 months [2-155]. The predominant histologic subtype was mucinous adenocarcinoma (58/60), 1 was colonic type, and 1 adenocarcinoid with signet ring cells. Four patients had extraperitoneal metastases, 2 hepatic metastases (1 with high-grade mucinous adenocarcinoma and 1 with colonic adenocarcinoma), and 2 in the low-grade group developed parenchymal lung disease. Three patients died in the postoperative period. Systemic chemotherapy was administered in 26 patients/57. No difference were observed in the OS and PFS regardless the use of SC in the high- and in the lo-grade groups. Conclusions: The use of SC in low-grade mucinous adenocarcinoma subtype is not supported by our results, and there is no literature date supporting it neither. Palliative SC in high-grade patients deserves of clinical trials for been accepted as standard of care, when benefits are not clearly established by evidence and toxicities are not negligible.

QUIMIOTERAPIA SISTÉMICA EN ADENOCARCINOMAS APENDICULARES CON METÁSTASIS PERITONEALES. ¿VALE LA PENA?

Introduction The role of systemic chemotherapy (SC) in the management of metastatic appendiceal adenocarcinomas is not defined. Methods We perform an observational study of patients treated of peritoneal metastases from appendiceal neoplasm between June 2004 and December 2017. They were referred to our hospital for CRS HIPEC. Systemic Chemotherapy regimens were decided by the referring oncologist. We analyze PCI, CC, and use of SC. Overall survival and progression free survival were compared attending to histologic subtype (high- and low-grade adenocarcinomas) and the use of SC. Results 60 patients were included, 26 were male, median age 63 years (26-81). Median follow-up of 38 months [2-155]. The predominant histologic subtype was mucinous adenocarcinoma (58/60), 1 was colonic type, and 1 adenocarcinoid with signet ring cells. Four patients had extraperitoneal metastases, 2 hepatic metastases (1 with high-grade mucinous adenocarcinoma and 1 with colonic adenocarcinoma), and 2 in the low-grade group developed parenchymal lung disease. Three patients died in the postoperative period. Systemic chemotherapy was administered in 26 patients/57. No difference were observed in the OS and PFS regardless the use of SC in the high- and in the lo-grade groups. Conclusions The use of SC in low-grade mucinous adenocarcinoma subtype is not supported by our results, and there is no literature date supporting it neither. Palliative SC in high-grade patients deserves of clinical trials for been accepted as standard of care, when benefits are not clearly established by evidence and toxicities are not negligible.

Glycomic Profiling Highlights Increased Fucosylation in Pseudomyxoma Peritonei

Pseudomyxoma peritonei (PMP) is a subtype of mucinous adenocarcinoma that most often originates from the appendix, and grows in the peritoneal cavity filling it with mucinous ascites. KRAS and GNAS mutations are frequently found in PMP, but other common driver mutations are infrequent. As altered glycosylation can promote carcinogenesis, we compared N-linked glycan profiles of PMP tissues to those of normal appendix. Glycan profiles of eight normal appendix samples and eight low-grade and eight high-grade PMP specimens were analyzed by mass spectrometry. Our results show differences in glycan profiles between PMP and the controls, especially in those of neutral glycans, and the most prominent alteration was increased fucosylation. We further demonstrate up-regulated mRNA expression of four fucosylation-related enzymes, the core fucosylation performing fucosyltransferase 8 and three GDP-fucose biosynthetic enzymes in PMP tissues when compared with the controls. Up-regulated protein expression of the latter three enzymes was further observed in PMP cells by immunohistochemistry. We also demonstrate that restoration of fucosylation either by salvage pathway or by introduction of an expression of intact GDP-mannose 4,6-dehydratase enhance expression of MUC2, which is the predominant mucin molecule secreted by the PMP cells, in an intestinal-derived adenocarcinoma cell line with defective fucosylation because of deletion in the GDP-mannose 4,6-dehydratase gene. Thus, altered glycosylation especially in the form of fucosylation is linked to the characteristic mucin production of PMP. Glycomic data are available via ProteomeXchange with identifier PXD010086.

GATA6-positive lung adenocarcinomas are associated with invasive mucinous adenocarcinoma morphology, hepatocyte nuclear factor 4α expression, and KRAS mutations.

GATA6 is known to play a role in lung development. However, its role in the carcinogenesis of lung cancer is not well studied. The aim of this study was to analyse GATA6 expression in lung adenocarcinomas (LAs) by immunohistochemistry (IHC) in order to define its association with clinicopathological characteristics. IHC analysis of GATA6 was performed with tissue microarray slides containing 348 LAs. The association between GATA6 expression and clinicopathological parameters was evaluated. GATA6 expression in epithelial tumours other than lung cancer was also evaluated. GATA6 expression was found in 47 LAs (13.5%). This occurred more frequently in younger patients (P = 0.005), and was associated with the absence of lymph node metastasis (P =0.024), well-differentiated to moderately differentiated tumours (P < 0.001), the absence of lymphatic invasion (P = 0.020), and the absence of vascular invasion (P = 0.011). GATA6 expression was associated with mucin production (P < 0.001), the invasive mucinous adenocarcinoma subtype (P < 0.001), KRAS mutations (P = 0.026), expression of MUC2 (P < 0.001), CDX2 (P = 0.049), and MUC5AC (P < 0.001), and absence of expression of TTF-1 (P = 0.002). GATA6 expression was also associated with hepatocyte nuclear factor 4α (HNF4α) expression (P < 0.001). GATA6 expression tended to indicate better prognoses, whereas patients with HNF4α expression had significantly worse prognoses (P = 0.033). Of 270 tumours other than lung cancer, 110 expressed GATA6. These findings suggest that GATA6 might interact with HNF4α and contribute to the development of mucinous-type LAs.

Villoglandulary papillary adenocarcinoma co-existing with high-grade squamous intraepitelial lesion; arising from an endocervical polyp

Adenocarcinomas account for 10–20% of invasive cervical carcinomas. The villoglandular papillary adenocarcinoma has been recognized as a subtype of mucinous adenocarcinoma and identified as a distinctive histological entity from the usual invasive adenocarcinomas of the uterine cervix. We report a new case of villoglandulary papillary adenocarcinoma, which was peculiar because of its association with a co-existing high grade squamous intraepithelial lesion and arising from an endocervical polyp. Excellent prognosis of isolated villoglandulary papillary adenocarcinoma is important in terms of making differential diagnosis from other adenocarcinomas and eliminating unnecessary aggressive treatments. It is also important to keep in mind for pathologists since it allows them to examine endocervical polyps that we often encounter in daily life and shows that malignant tumoral lesions can develop from polyps.

Multiple components of PKA and TGF-β pathways are mutated in pseudomyxoma peritonei.

Pseudomyxoma peritonei (PMP) is a subtype of mucinous adenocarcinoma mainly restricted to the peritoneal cavity and most commonly originating from the appendix. The genetic background of PMP is poorly understood and no targeted treatments are currently available for this fatal disease. While RAS signaling pathway is affected in most if not all PMP cases and over half of them also have a mutation in the GNAS gene, other genetic alterations and affected pathways are, to a large degree, poorly known. In this study, we sequenced whole coding genome of nine PMP tumors and paired normal tissues in order to identify additional, commonly mutated genes and signaling pathways affected in PMP. These exome sequencing results were validated with an ultra-deep amplicon sequencing method, leading to 14 validated variants. The validated results contain seven genes that contribute to the protein kinase A (PKA) pathway. PKA pathway, which also contains GNAS, is a major player of overproduction of mucin, which is the characteristic feature of PMP. In addition to PKA pathway, we identified mutations in six genes that belong to the transforming growth factor beta (TGF-β) pathway, which is a key regulator of cell proliferation. Since either GNAS mutation or an alternative mutation in the PKA pathway was identified in 8/9 patients, inhibition of the PKA pathway might reduce mucin production in most of the PMP patients and potentially suppress disease progression.

Mucinous Colorectal Adenocarcinoma: Influence of EGFR and E-Cadherin Expression on Clinicopathologic Features and Prognosis.

Previous studies have shown conflicting results on epidermal growth factor receptor (EGFR) and E-cadherin expression in colorectal carcinoma and their prognostic significance. To the best of our knowledge, this study is the first to investigate EGFR and E-cadherin expression, interrelation and relation to clinicopathologic, histologic parameters, and survival in rare colorectal mucinous adenocarcinoma (MA). In this study, we studied tumor tissue specimens from 150 patients with colorectal MA and nonmucinous adenocarcinoma (NMA). High-density manual tissue microarrays were constructed using modified mechanical pencil tips technique, and immunohistochemistry for EGFR and E-cadherin was performed. All relations were analyzed using established statistical methodologies. NMA expressed EGFR and E-cadherin in significantly higher rates with significant heterogenous pattern than MA. EGFR and E-cadherin positivity rates were significantly interrelated in both NMA and MA groups. In the NMA group, high EGFR expression was associated with old age, male sex, multiplicity of tumors, lack of mucinous component, and association with schistosomiasis. However, in the MA group, high EGFR expression was associated only with old age and MA subtype rather than signet ring carcinoma subtype. Conversely, high E-cadherin expression in MA cases was associated with old age, fungating tumor configuration, MA subtype, and negative intratumoral lymphocytic response. However, in the NMA cases, none of these factors was statistically significant. In a univariate analysis, neither EGFR nor E-cadherin expression showed a significant impact on disease-free or overall survival. Targeted therapy against EGFR and E-cadherin may not be useful in patients with MA. Neither EGFR nor E-cadherin is an independent prognostic factor in NMA or MA.

A case of gastric-type adenocarcinoma of the uterine cervix associated with lobular endocervical glandular hyperplasia: radiologic–pathologic correlation

Gastric-type adenocarcinoma (GAS) of the uterine cervix is a recently defined subtype of mucinous adenocarcinoma. GAS is proposed to include minimal deviation adenocarcinoma (MDA) as a very well-differentiated form and has been suggested to arise from lobular endocervical glandular hyperplasia (LEGH). We report the magnetic resonance imaging (MRI) findings of a GAS associated with LEGH. On MRI, the LEGH component was detected as multiple cystic lesions arranged in a "cosmos pattern", while the GAS was depicted as a predominantly solid lesion containing obvious adenocarcinoma and MDA components, which appeared as mass-like and infiltrative components, respectively. The GAS exhibited tiny cysts on three-dimensional T2-weighted images, high intensity on diffusion-weighted images mostly due to T2 shine-through effect according to apparent diffusion coefficient (ADC) map, and reticular enhancement on dynamic contrast-enhanced MRI, which reflected numerous dilated glandular structures of the tumor. Low ADC was only observed at the deepest invasion front of the obvious adenocarcinoma component. Our case suggests that the MRI features of GAS vary depending on the tumor's histological components, and it is important to be aware of these imaging features when evaluating LEGH on MRI.

924P - Recurrence Patterns of Gastric-Type Adenocarcinoma (Gas) of the Uterine Cervix: a Subset Analysis of the Gynecologic Cancer Study Group of the Japan Clinical Oncology Group (Jcog) Gas Multicenter Study

ABSTRACT Aim: We previously reported that gastric-type adenocarcinoma (GAS), a subtype of mucinous adenocarcinoma of the cervix, is more significantly associated with histopathological predictors of poor outcomes as well as with poorer survival outcomes than is usual-type endocervical adenocarcinoma (UEA). It is therefore clinically important to distinguish GAS from UEA (ASCO 2014). However, the cause of its aggressive nature remains unknown. We therefore studied the aggressive nature of GAS in patients with disease recurrence. Methods: Patients were enrolled at the Gynecologic Cancer Study Group of the JCOG after receiving approval from an internal review board. Among 393 women with adenocarcinoma of the cervix who were enrolled, 328 with mucinous adenocarcinoma of the cervix who met the central pathological review (CPR) and eligibility criteria were included in analysis. GAS was diagnosed in 95 (28.9%) of the 328 patients. Sites of recurrence of GAS and UEA and the response to treatment (chemotherapy, radiotherapy) given after recurrence were analyzed using statistical techniques. Treatment response was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST). Results: Overall, recurrence occurred in 72 of the 328 patients: 38 (40%) of 95 patients with GAS and 34 (14.6%) of 233 patients with UEA. Recurrence was clearly more common among patients with GAS (p = 0.0023). In the GAS group, the sites of recurrence were local in 15 patients, distant in 15, and local plus distant in 8. In the UEA group, the sites of recurrence were local in 19 patients, distant in 11, and local plus distant in 4, with no significant difference between the groups. After recurrence, chemotherapy was given to 19 patients with GAS, with a response rate of 36.8% (7/19), and 25 patients with UEA, with a response rate of 32.0% (8/25). The difference in response rates was not significant. Radiotherapy was given to 12 patients with GAS, with a response rate of 50.0% (6/12), and 11 patients with UEA, with a response rate of 81.8% (9/11, p Conclusions: Sites of recurrence sites and the response to chemotherapy did not differ significantly between patients with GAS and those with UEA who had recurrence. Resistance to radiotherapy may reflect the aggressive nature of GAS. Disclosure: All authors have declared no conflicts of interest.

Mucinous neoplasms of the appendix: A single-center experience.

368 Background: Appendiceal neoplasms are poorly understood and represent less than 0.5% of all gastrointestinal cancers. We describe the presentation, pathologic characteristics, and treatment interventions that may have affected patient (pt) outcome. Methods: This is a retrospective review of pts with appendiceal neoplasms treated at NYU Medical Center and/or NYU Cancer Center between 2002-2011. Pt demographics and medical history were collected, including pathology reports, operative findings, imaging studies, treatment and outcomes. Results: 41 consecutive pts with varying stages of appendiceal cancer were identified (70.7% female, median age 57). Most common presentations included: 15 (36.6%) gynecologic complaints, 12 (29.2%) acute appendicitis, and 11 (26.8%) abdominal symptoms. Histologic subtypes were 27 (65.9%) mucinous cystadenomas and 14 (34.1%) adenocarcinomas of which 12 (29.3%) were mucinous adenocarcinoma and 2 (4.9%) were signet cell mucinous adenocarcinoma. Distribution of stages was: 27 (65.9%) stage 0, 2 (4.9%) stage I, 2 (4.9%) stage IIA/B, 6 (14.6%) stage IVA, and 4 (9.8%) stage IVB. All pts underwent one or more of the following procedures: appendectomy (n=39), colectomy (n=9), bilateral salpingo-oophorectomy (n=4), other (n=1). 9 of 10 stage IV pts underwent debulking, of those 2 had suboptimal debulking. 1 stage II pt and 4 stage IV pts (all mucinous adenocarcinoma subtype) received hyperthermic intraperitoneal chemotherapy (HIPEC) with mitomycin-C (all female, median age 39). In contrast, 6 stage IV pts (2 signet cell adenocarcinoma, 4 mucinous adenocarcinoma subtypes) did not receive HIPEC (67% female, median age 80). 1 pt received systemic 5FU based chemotherapy in addition to HIPEC (female, age 39). Median overall survival (mOS) for all pts ≥ stage II is 32 months. mOS in pts ≥ stage II who did not receive HIPEC is 8 mo whereas mOS in pts ≥ stage II who received HIPEC has not been reached. Conclusions: Appendiceal cancer is frequently detected as an incidental finding for gynecologic and abdominal complaints or presents as acute appendicitis. Surgery is the mainstay of treatment for this disease. Additional therapy including HIPEC may be of benefit in select advanced stage patients.

Adenoma malignum of the uterine cervix: Imaging features with clinicopathologic correlation

Adenoma malignum, also known as minimal deviation adenocarcinoma, is a subtype of mucinous adenocarcinoma of the cervix. To evaluate the clinical, pathologic, and imaging features of the adenoma malignum of the uterine cervix. We retrospectively analyzed the CT and MRI findings in 13 patients: size, endoluminal fluid, appearance of the solid and cystic component, margin, enhancement, characteristics of locules of the cystic lesion, tumor spread, and associated ovarian lesion. Clinical and pathologic features were determined in 24 patients. The mean of the major tumor diameter was 4.1 cm (range, 2.2-6.5 cm). In the imaging features, 77% of 13 tumors demonstrated endoluminal fluid. All tumors showed enhancing solid components; 62% were multicystic and 38% had solid lesions. Most solid lesions exhibited an irregular margin (80%). The locules of the multicystic lesions tended to have smooth margins (75%), to have an average major diameter of ≤1 cm (88%), and to be 11-20 in number (75%). The solid lesions were associated with invasion and metastases (60%). Clinically, 38% of 24 patients had watery discharge and 13% had Peutz-Jeghers syndrome, while pathologically, most patients were low stage (I or II) (83%). Over the 2-year follow-up of 17 patients, 82% was free from disease. The patients with more aggressive tumors or an unfavorable prognosis that manifested as tumor recurrence or metastasis tended to have invasion, watery discharges, high stages (III or IV) (100%) and solid lesions, metastases, and associated ovarian lesions (67%). Awareness of imaging features as well as clinicopathologic manifestations of adenoma malignum can aid in accurate diagnosis, treatment, and prediction of prognosis.

Primary Vaginal Mucinous Adenocarcinoma of Gastric Type Arising in Adenosis

We report 2 cases of primary vaginal mucinous adenocarcinoma arising in adenosis in nondiethylstilbestrol-exposed women, 1 with uterus didelphys. Both tumors exhibited morphologic and immunohistochemical features (MUC6 and/or HIK 1083 positivity) identical to the recently described cervical gastric-type adenocarcinoma, a subtype of mucinous adenocarcinoma that is non-human papillomavirus related and possibly related to adenoma malignum. Both neoplasms were intensely p53 positive, suggesting that TP53 mutation may be implicated in their development. We believe that the vaginal tumors arose from adenosis through atypical adenosis, as benign and atypical glands were present at the periphery of the neoplasms. In reporting these cases, we discuss atypical adenosis and other types of non-diethylstilbestrol-associated vaginal adenocarcinomas. At least 9 other examples of primary vaginal, or more uncommonly cervical, adenocarcinomas arising in non-diethylstilbestrol-exposed women with congenital genitourinary malformations have been reported, suggesting a probable causal association between congenital malformation, vaginal adenosis, and vaginal adenocarcinoma.