Poorly-differentiated Adenocarcinoma Research Articles

Verrucous gastritis-like lesion in intramucosal Helicobacter pylori-uninfected signet ring cell carcinoma with poorly differentiated adenocarcinoma

In Japan, accessible Helicobacter pylori (Hp) eradication therapy is associated with an increase in the prevalence of gastric cancers (GCs) in Hp uninfected stomachs. Signet ring cell carcinoma (SRCC) is the most common of these GCs. Intramucosal SRCC with poorly differentiated adenocarcinoma (PDA) occurring in Hp uninfected gastric mucosa is rare; furthermore, many Hp uninfected pure SRCCs exhibit discoloration and flat or slightly depressed lesions, and morphological elevation is relatively rare. We report a case of intramucosal SRCC with PDA with an elevated, verrucous gastritis-like lesion in a 57-year-old male patient. In the present case, the PDA area showed dense tumor cell growth and coexisting desmoplastic and fibrotic reactions. Histopathology and immunohistochemical staining identified extensive fibromuscular obliteration with smooth muscle bundles extending from the muscularis mucosa into the lamina propria. The patient underwent curative endoscopic submucosal dissection. The reporting and analysis of such rare cases may lead to a better understanding of the characteristics of advanced Hp uninfected GCs.

Clinicopathological significance of microsatellite instability and immune escape mechanism in patients with gastric solid-type poorly differentiated adenocarcinoma.

In gastric solid-type poorly differentiated adenocarcinoma (PDA), the role of microsatellite instability and immune escape mechanism remains unclear. The current study aimed to elucidate the clinical significance of mismatch repair (MMR) status, genome profile, C-X-C motif chemokine receptor 2 (CXCR2) expression, and myeloid-derived suppressor cell (MDSC) infiltration in solid-type PDA. In total, 102 primary solid-type PDA cases were retrieved, and classified into 46 deficient-MMR (dMMR) and 56 proficient-MMR (pMMR) cases based on immunohistochemistry (IHC) and polymerase chain reaction-based molecular testing results. The mRNA expression profiles (NanoString nCounter Assay) of stage-matched dMMR (n = 6) and pMMR (n = 6) cases were examined. The CXCR2 expression and MDSC infiltration (CD11b- and CD33-positive cells) were investigated via IHC in all solid-type PDA cases. mRNA analysis revealed several differentially expressed genes and differences in biological behavior between the dMMR (n = 46) and pMMR (n = 56) groups. In the multivariate analysis, the dMMR status was significantly associated with a longer disease-free survival (hazard ratio = 5.152, p = 0.002) and overall survival (OS) (hazard ratio = 5.050, p = 0.005). CXCR2-high expression was significantly correlated with a shorter OS in the dMMR group (p = 0.018). A high infiltration of CD11b- and CD33-positive cells was significantly correlated with a shorter OS in the pMMR group (p = 0.022, 0.016, respectively). dMMR status can be a useful prognostic predictor, and CXCR2 and MDSCs can be novel therapeutic targets in patients with solid-type PDA.

Primary Endometrial Carcinoma with Signet Ring Cells: A Rare and Unusual Entity

Abstract Introduction/Objective The presence of signet ring cells in an endometrial tumor is suggestive of metastasis, as primary tumors with this morphology are extremely rare. As a result, primary tumors are a diagnosis of exclusion, defined by the presence of signet-ring cells usually associated with mucinous endometrioid carcinoma without clinical or radiographic evidence of metastases from breast, stomach, or colon. Methods/Case Report A 64-year-old woman presented with vaginal bleeding. Ultrasound showed a large, heterogenous uterine mass that was diagnosed as poorly differentiated carcinoma on biopsy. Serum CEA was elevated, and CA-125 was normal. Hysterectomy with salpingo-oophorectomy showed a minor endometrial component of grade 3 endometrioid carcinoma and a predominant component of poorly differentiated carcinoma with signet ring cells. The myoinvasive component consisted of the signet ring cells with pools of acellular mucin. Extensive lymphovascular invasion was noted. Cervix, adnexa, and lymph nodes were free of disease. The signet ring cells were positive for CK7, CK20, and CDX2, and negative for ER and Pax-8. The endometrioid component was positive for ER, Pax-8, and CK7, and negative for CK20 and CDX2. E-cadherin staining was lost in the myoinvasive component of the tumor. Loss of MLH1 and PMS2 nuclear expression was seen, and MLH1 promoter methylation was detected in both components of the tumor. Subsequent colonoscopy and imaging did not reveal any other disease sites. Based on histology, pattern of uterine involvement, and lack of extrauterine disease, a diagnosis of primary poorly-differentiated endometrial adenocarcinoma with signet ring cell features was made. The patient was treated with adjuvant chemotherapy and is currently being followed. Results (if a Case Study enter NA) NA Conclusion We present a rare case of primary signet ring carcinoma of the uterus, a challenging diagnosis made after extensive work-up to rule out metastases. Of the previous 9 reported cases, only one was similar to our tumor with distinct endometrioid and signet ring components. Although these primary endometrial tumors are unified by the presence of signet ring cells, there is considerable immunohistochemical heterogeneity. Some reports suggest the signet ring cells have a Mullerian phenotype, while others, including our case, suggest a gastrointestinal phenotype. In presenting this case, we hope to contribute to this entity’s characterization and bring further awareness that the presence of signet ring cells does not exclude a uterine primary.

Tumor Differentiation as a Prognostic Marker in Clinically Staged T1bN0 Esophageal Adenocarcinoma

Current guidelines recommend that clinically staged T1N0 esophageal cancers are to be referred to surgery or endoscopic resection. Using the National Cancer Database, we identified 733 individuals with clinically staged T1N0 esophageal carcinoma, who underwent upfront surgery and did not receive any prior treatment. We assessed upstaging, which was defined as ≥ T2 disease or positive lymph nodes. Poorly differentiated adenocarcinomas were associated with upstaging, whereas squamous cell carcinomas were not. Specifically, the percentage of upstaging among individuals with clinically staged T1b and poorly differentiated tumor was 33.8%. Therefore, clinically staged T1bN0 poorly differentiated esophageal adenocarcinomas are at high risk for upstaging following surgery.

Skip metastasis at the esophageal resection margin in radical gastrectomy: clinical characteristics of 30 cases

Objective: To summarize the clinical characteristics of patients with skip metastasis at esophageal resection margin during radical gastrectomy. Methods: This is a descriptive study of case series. Relevant data from 2006 to 2022 were collected from two major gastric cancer consultation and treatment centers: Nanjing Drum Tower Hospital and Jinling Hospital.Characteristics, surgical approach, number of dissected lymph nodes, immunohistochemical staining, and pathological staging were summarized and analyzed. The distribution of residual tumor cells at the esophageal margins was further analyzed at the cellular and tissue levels. Skip metastasis at the esophageal resection margin was defined as a negative esophageal margin with a positive margin in the cephalad donut. Results: Thirty (0.33%, 30/8972) eligible patients, 24 (80.0%) of whom were male, were identified in the two centers. The mean age was 63.9±11.0 years. Seventeen (56.7%) of these patients had papillary or tubular adenocarcinomas, including 13 (43.3%) poorly- and four (13.3%) moderately-differentiated tumors; four (13.3%) had signet-ring cell carcinomas; four (13.3%) mucinous adenocarcinomas; three (10.0%) mixed adenocarcinomas, including two with poorly-differentiated tubular adenocarcinomas mixed with signet-ring cell carcinoma and mucinous adenocarcinoma; and one had a poorly differentiated tubular adenocarcinoma mixed with signet-ring cell carcinoma. Two patients (6.7%) had other types of cancer, namely adenosquamous carcinoma in one patient and undifferentiated carcinoma in the other one. The predominant tumor sites were the lesser curvature (n=26, 86.7%) and the cardia (n=24, 80.0%). The mean tumor diameter was 6.6 cm, mean distance between tumor and esophageal resection margin was 1.5 cm, and proportions of tumor invasion into the dentate line, nerves, and vessels were 80.0% (24/30), 86.7%(26/30), and 93.3% (28/30), respectively. The mean number of lymph nodes resected was 20.4±8.9. The pathological stage was mainly T4 (n=18, 60.0%) and N3 (n=21, 70.0%), the median Ki67 was 52.7%, and the rates of positivity for HER2, EGFR, VEGFR, E-cadherin and PD-L1 were 40.0% (12/30), 46.7% (14/30), 80.0% (24/30), 86.7% (26/30) and 16.7% (5/30), respectively. At the cellular level, cancer cells were mainly distributed in small focal areas, as cell masses, or as tumor thrombi; large numbers of widely distributed atypic cells were seldom observed. At the tissue level, cancer cells were located in the mucosal layer in seven patients (23.3%), in the submucosal layer in 18 (60.0%), and in the muscular layer in five (16.7%); no cancer cells were identified in the outer membrane. Five of the seven tumors were located in the lamina propria, two in the muscularis mucosae, and none in the mucosal epithelium. Conclusion: Patients with skip metastasis at the esophageal resection margin at radical gastrectomy have unfavorable tumor biology and a high proliferation index, are at a late pathological stage, and the residual cancer is mostly located in the submucosa.

Combined Metronomic Chemo-Immunotherapy in Metastatic Carcinoma of Esophagus in Second Line and Beyond

Background and Aims: Approximately 570,000 new cases are diagnosed with esophageal cancer worldwide annually and approximately 510,000 deaths from this disease per year. There are currently no effective second-line treatments for patients who progress on cisplatin and 5-fluorouracil. Esophageal squamous cell carcinomas and adenocarcinomas have proven to be inherently resistant to systemic treatments as a result of histological, molecular and etiological heterogeneity, with limited responses seen after first line therapy. Methods: We are presenting 3 case reports of 57 year old man, 53 year old man & 47 year old woman who, presented with dysphasia for solid foods, weight loss and dyspepsia since 1 month, 3 months & 1.5 months respectively. Upper gastro oesophageal endoscopy shows ulcerated friable lesion with minimal luminal compromise with biopsy showing poorly differentiated adenocarcinoma (PDAC) and PECT-CT showed FDG avid lesions in gastroesophageal junction, gastric cardia, multiple retroperitoneal lymph nodes and bilateral liver lesions. All 3 were having stage IV disease, with PDAC, squamous cell carcinoma & PDAC respectively. We have started 1st patient on DOX regimen containing Docetaxel, Oxaliplatin and Capecitabine at an interval of 2 weeks and after 4 cycles he was having stable disease in GE junction, liver and slightly increased size of retroperitoneal lymph nodes. Second & 3rd patient was put on Pclitaxel-carboplatil protocol, after 6 cycles both were having partial response & was managed with 6 cycles CAPOX as second line che otherapy. After 5th & 6th months of second line chemotherapy both patients were having progressive disease. Results: In view of radiological progression we started him on Injection, Nivolumab 240mg intravenously every 2 weekly along with low dose capecitabine 500mg twice a day. After 4 cycles of treatment his PET-CT showing complete metabolic response in GE junction, liver and retroperitoneal lesions. Now we are continuing Nivolumab and low dose capecitabine planned to complete for 2 years. Conclusion: So to conclude nivolumab along with metronomic chemotherapy with low dose capecitabine was very well tolerated and exhibited antitumor activity in extensively pretreated patient with metastatic esophageal poorly differentiated adenocarcinoma. Additional studies of Nivolumab and metronomic chemotherapy and immuno-immuno combination therapy in these diseases are ongoin.

S2040 Hiding in Plain Sight: The Challenge of Diagnosing Medullary Carcinoma of the Colon

Introduction: Medullary carcinoma of the colon (MCC) represents < 3% of colon cancers and is characterized by microsatellite instability (MSI) leading to poor cellular differentiation. With its relative rarity and ambiguous histology, MCC remains a challenging, frequently-missed diagnosis. Case Description/Methods: A 56-year-old post-menopausal female with asymptomatic iron-deficiency anemia was referred to gastroenterology for bidirectional endoscopy. Colonoscopy identified multiple colonic polyps and a mass nearly obstructing the ascending colon. Abdominopelvic CT showed an 8.1 cm mass with associated mesenteric lymph nodes but no extracolonic involvement. CEA levels were normal. Initial biopsy demonstrated poor tumor differentiation. Immunohistochemical staining was positive for CD45, a marker of lymphocytic infiltration, but negative for cytokeratin (CK) 20, caudal-related homeobox gene 2 (CDX-2), and synaptophysin, interpreted as an undifferentiated carcinoma. The patient was referred to colorectal surgery and underwent laparoscopic right hemicolectomy without complication. Biopsy of the resected tumor redemonstrated the initial biopsy results without lymph node involvement. Additional stains showed high MSI and negativity for extracolonic tumor markers. These findings confirmed the tumor as a non-adenocarcinoma primary colonic lesion suggestive of MCC. Discussion: The differential diagnosis for poorly-differentiated colonic tumors includes poorly-differentiated adenocarcinoma (PDA), neuroendocrine tumor (NET), MCC, and metastasis. This ambiguity has led to tumor misidentification in up to 66% of MCC cases; however, several key features can distinguish among these carcinomas. MCC displays negative chromogranin and synaptophysin staining, unlike NET. MCC almost invariably has high MSI and is infrequently CK20 and CDX-2 positive, unlike PDA. Clinically, MCC is more likely to present in the eighth decade, in females, and in the right colon than NET or PDA. MCC frequently follows an indolent course with good prognosis, while PDA often grows and spreads aggressively. While this case had a uniquely young age of presentation, it otherwise exhibits known clinical and histological features of MCC. As familiarity with these features rises and the use of MSI testing expands, accurate diagnosis of MCC will likely improve. With the expansion of colon cancer screening, the incidence of MCC is likely to rise, highlighting the importance of timely, accurate diagnosis when facing poorly-differentiated colonic tumors.

S3704 A Case of Back Pain as the Presenting Symptom of Metastatic Gastric Adenocarcinoma in a Young Male

Introduction: Gastric adenocarcinoma typically occurs in the fifth to seventh decades of life, with only 5% of patients diagnosed before age forty. Most common presenting symptoms include weight loss, abdominal pain, and bleeding. There are limited publications describing gastric cancer (GC) in younger patient populations, especially those with atypical presentations. Case Description/Methods: A 29-year-old male with no significant medical history presented to his general practitioner with back pain for 2 months. Outpatient magnetic resonance imaging (MRI) of his lumbar spine was concerning for metastatic cancer, so he was sent to the emergency department for evaluation. Lab testing showed normocytic anemia of 10.3 g/dL, elevated alkaline phosphatase level of 744, and uric acid level of 10.7. Complete MRI views of his spine demonstrated extensive osseous metastatic disease in his cervical, thoracic, lumbar, and sacral regions (Figure 1A). The patient underwent computed tomography-guided biopsy of the metastatic lesions in his right sacrum. Immunohistochemical staining was suggestive of upper gastrointestinal or pancreaticobiliary malignancy. Therefore, he underwent endoscopic evaluation. Upper endoscopy revealed congestive gastropathy in the cardia and fundus, suspicious for infiltrative pathology, which was biopsied (Figure 1B). Endoscopic ultrasound revealed subtle wall thickening at the gastroesophageal junction and few small lymph nodes in the peri-pancreatic and celiac region. Pathology confirmed poorly-differentiated gastric adenocarcinoma (Figure 1C). H Pylori staining was negative. The patient has since been started on palliative chemotherapy and radiation. Discussion: We report here a unique presentation of GC in a young patient. To our knowledge this is the only case described thus far that reviews a young male presenting with chronic back pain as the first symptom of metastatic GC. Apart from typically being found in older populations, GC usually presents with symptoms of weight loss or gastrointestinal complaints. This patient’s presenting symptom was back pain from his bony metastases. As GC remains a leading cause of death from cancer worldwide, this case demonstrates that it is an important consideration in patients presenting with signs and symptoms concerning for malignancy of unclear origin, including patients of a younger demographic. Additionally, chronic back pain should be thoroughly investigated including in younger individuals to avoid missing clinically significant conditions.Figure 1.: [A] Magnetic resonance imaging of spine showing extensive osseous metastatic disease. [B] Upper endoscopy with congestive gastropathy. [C] Pathology demonstrating poorly-differentiated gastric adenocarcinoma.

Expression of M3 muscarinic acetylcholine receptors in gastric cancer.

Introduction: Gastric cancer represents a real public health problem as far as incidence, aggressiveness and unfavorable prognosis are concerned. The autonomous nervous system might be one of the major factors involved in the onset, progression, and metastasis, both sympathetically and parasympathetically. The increased activation of the M3 muscarinic acetylcholine receptors (mAChRs) triggers pro-oncogenic mechanisms, especially at a gastric level, through the activation of the Hippo signaling pathway and the increase of the nerve growth factor. Patients, Materials and Methods: In this study, biopsy or postoperative gastric resection pieces have been evaluated by histopathological (HP) and immunohistochemical (IHC) examination in a group of 77 gastric patients and 23 patients without an oncological diagnosis. To quantify the IHC signal, also considering the HP aspect, light microscopy images were obtained. Results: The M3 mAChR expression analysis has been correlated with the different gastric adenocarcinoma differentiation degrees (G1–G3). M3 mAChR presence has been observed also in the non-malignant gastric tissue, but it was significantly increased in the tumor tissue. The highest receptor expression was recorded in patients with a poorly-differentiated (G3) adenocarcinoma, these expressions decreasing with the increase of the differentiation degree towards moderately-differentiated (G2) and well-differentiated (G1). Conclusions: Surgical or pharmacological parasympathetic activity inhibition could decrease the development and progression of gastric tumors and could improve the gastric cancer patient’s prognosis.

Interpretable tumor differentiation grade and microsatellite instability recognition in gastric cancer using deep learning

AbstractGastric cancer possesses great histological and molecular diversity, which creates obstacles for rapid and efficient diagnoses. Classic diagnoses either depend on the pathologist's judgment, which relies heavily on subjective experience, or time-consuming molecular assays for subtype diagnosis. Here, we present a deep learning (DL) system to achieve interpretable tumor differentiation grade and microsatellite instability (MSI) recognition in gastric cancer directly using hematoxylin-eosin (HE) staining whole-slide images (WSIs). WSIs from 467 patients were divided into three cohorts: the training cohort with 348 annotated WSIs, the testing cohort with 88 annotated WSIs, and the integration testing cohort with 31 original WSIs without tumor contour annotation. First, the DL models comprehensibly achieved tumor differentiation recognition with an F1 values of 0.8615 and 0.8977 for poorly differentiated adenocarcinoma (PDA) and well-differentiated adenocarcinoma (WDA) classes. Its ability to extract pathological features about the glandular structure formation, which is the key to distinguishing between PDA and WDA, increased the interpretability of the DL models. Second, the DL models achieved MSI status recognition with a patient-level accuracy of 86.36% directly from HE-stained WSIs in the testing cohort. Finally, the integrated end-to-end system achieved patient-level MSI recognition from original HE staining WSIs with an accuracy of 83.87% in the integration testing cohort with no tumor contour annotation. The proposed system, therefore, demonstrated high accuracy and interpretability, which can potentially promote the implementation of artificial intelligence healthcare.

Correlation of LGR5 expression and clinicopathological features in intrahepatic cholangiocarcinoma

Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) is a known cancer stem cell marker. However, there are no reported analyses of LGR5 mRNA expression in normal liver and liver cancer tissues. Here, we evaluated LGR5 expression by RNAscope, a newly developed RNA in situ hybridization technique, using a tissue microarray consisting of 25 samples of intrahepatic cholangiocarcinoma (ICC) selected from the medical archives at our hospital. LGR5 expression levels were divided into high and low expression groups by the five-grade scoring system, and clinicopathological features were analyzed. Low LGR5 expression was identified in some normal hepatocytes and bile duct cells. In addition, LGR5 expression was identified in all bile duct cancer samples except one case. Well-differentiated to moderately-differentiated adenocarcinoma tended to show higher LGR5 expression than poorly-differentiated adenocarcinoma (P = 0.0561), and the large duct type showed significantly higher LGR5 expression levels than the small duct type (P = 0.0225). Patients in the high LGR5 expression group tended to have good overall survival (OS) (P = 0.0623). The Cox proportional hazard regression model revealed that the high LGR5 expression group showed independently better OS for ICC (P = 0.0285). High LGR5 expression is possibly a good prognosis factor in ICC. However, the detailed mechanism of LGR5 in this disease remains unclear, and further analysis is warranted.

Risk stratification for predicting postoperative recurrence/metastasis of colorectal cancer by grade of venous invasion coupled with histological subtype

BackgroundColorectal cancer (CRC) consists of several histological subtypes that greatly affect prognosis. Venous invasion (VI) has been implicated in the postoperative recurrence of CRC, but the relationship between the VI grade and postoperative recurrence in each histological subtype has not been clarified thus far.MethodsA total of 323 CRCs without distant metastasis at surgery (pathologic stage III or lower), including 152 well-to-moderately differentiated adenocarcinomas (WMDAs), 98 poorly differentiated adenocarcinomas (PDAs), and 64 mucinous adenocarcinomas (MUAs), were analyzed. They were routinely processed pathologically, and VI was graded as follows irrespective of location by elastica van Gieson staining: v0 (none), no venous invasion; v1 (mild), 1–3 invasions per glass slide; v2 (moderate), 4–6 invasions per glass slide; and v3 (severe), ≥ 7 invasions per glass slide. Filling-type invasion in veins with a minor axis of ≥ 1 mm increased the grade by 1. The association of VI grade with prognosis was statistically analyzed.ResultsAll recurrences occurred as distant metastases. Recurrence increased with VI grade in WMDA (v0 11.8%, v1 15.8%, v2 73.9%, v3 75.0%) and MUA (v0 15.2%, v1 30.8%, v2 40.0%). The recurrence rate was relatively high in PDA even with v0 and increased with VI grade (v0 27.8%, v1 32.7%, v2 33.3%, v3 60.0%). VI grade was a significant predictor of recurrence in WMDA but not in PDA and MUA by multivariate analysis. In node-negative (stage II or lower) CRC, the recurrence-free survival (RFS) rate exceeded 90% in v0 and v1 WMDA until postoperative day (POD) 2100 and v0 MUA until POD 1600 but fell below 80% in the other settings by POD 1000. In node-positive (stage III) CRC, the RFS rate fell below 80% in all histological subtypes by POD 1000.ConclusionsVI grade v1 had a similar recurrence rate and RFS as grade v0 and may not warrant adjuvant chemotherapy in node-negative (stage II or lower) WMDA. In addition to node-positive (stage III) CRC, adjuvant chemotherapy may be indicated for node-negative (stage II or lower) CRC when it is WMDA with VI grade v2 or v3, MUA with VI, or PDA.

Induction of Premalignant and Malignant Changes in Nude Mice by Human Tumors-Derived Cell-Free Filtrates

Carcinogenesis is a vast and heterogeneous, multi-step process driven by genetic and epigenetic operators leading to superimposed “tumor organs”. Based on our previous experiences of reproducing human donor’s histopathological hallmarks in healthy animals exposed to pathologic tissues homogenates, we examined the consequences of administering crude homogenates elaborated from invasive human tumors to nude mice. Subcutaneous administrations of increasing protein concentrations of breast carcinoma homogenates for 6 and 12 weeks, induced lungs atypical adenomatous hyperplasia, foci of lepidic and solid growth poorly-differentiated adenocarcinomas at the two time points. Non-atypical mucosal hyperplasia and adenomas were detected along the gastrointestinal tract. Another experiment addressed the impact of daily administrations (100 μg protein/mouse) of anaplastic sarcoma tissue homogenate for a month. This scheme triggered proliferative changes including: lung adenocarcinomas; a subcutaneous, poorly-differentiated mesenchymal cells tumor, a lymphoadenoma, and multiple gastrointestinal adenomas. When 50% of the month-treated animals were left to evolve treatment-free for other 35 days, a larger and broader incidence of neoplastic changes was found, suggesting autonomous growth: lung adenocarcinomas, a poorly differentiated thyroid tumor, an epithelial tumor within the periaortic brown adipose tissue, and multiple adenomas. These findings indicate that tumor crude homogenates contains soluble “transforming” messengers, that in a short period of time disrupt tissues’ proliferative and differentiation programs drifting to progressive neoplasms. This study expands previous evidences on the ability of human pathologic tissues-derived homogenates, to induce the reproduction of diseased donor’s histopathologic hallmarks.

Tumor progression by epithelial-mesenchymal transition in ARID1A- and SMARCA4-aberrant solid-type poorly differentiated gastric adenocarcinoma.

Solid-type poorly differentiated adenocarcinoma (PDA) of the stomach is frequently associated with microsatellite instability (MSI) and aberrations of the SWI/SNF chromatin remodeling complex. Previous studies showed that aberrant ARID1A and SMARCA4 expression induces mesenchymal transition. We analyzed 51 primary-site cases and 209 metastatic lymph nodes among solid-type PDA for the expression of SWI/SNF complex subunits (ARID1A, SMARCA4, SMARCB1, SMARCC2) and epithelial-mesenchymal transition (EMT) markers (E-cadherin, β-catenin, Snail). We also analyzed 40 cases of non-solid-type PDA as a stage-matched control group. Aberrant expression of ARID1A (39%) and SMARCA4 (49%) was more common in solid-type PDA than in non-solid-type PDA (ARID1A, P = 0.0049; SMARCA4, P < 0.0001). The group of solid-type PDA with aberrant ARID1A showed significantly longer overall and progression-free survival than the corresponding ARID1A-retained group (P = 0.0405 and P = 0.0296, respectively). Aberrant expression of EMT factors inducing mesenchymal transition in the groups with solid-type PDA at the primary site or metastatic lymph nodes with aberrant ARID1A was less common than in the corresponding groups with retained ARID1A (E-cadherin, primary site P = 0.0341, lymph node P < 0.0001; β-catenin, primary site P = 0.0293, lymph node P = 0.0010; Snail, primary site P = 0.0169, lymph node P = 0.0828). Furthermore, N3 of the TNM classification was more frequently observed in the group with solid-type PDA with retained ARID1A than in the corresponding ARID1A-aberrant group (P = 0.0288). Mesenchymal transition was not induced in the ARID1A-aberrant group, in which patients had favorable prognosis, and preserved epithelial characteristics in EMT may play an important role in low tumor aggressiveness of solid-type PDA.

Diagnosis of Advanced Disease in Cases of Colorectal Cancer in a Developing Country

Abstract Objectives Colorectal cancer (CRC) is the second leading cause of cancer death in the world, with survival correlated with the extension of the disease at diagnosis. In many low-/middle-income countries, the incidence of CRC is increasing rapidly, while decreasing rates are observed in high-income countries. We evaluated the anatomopathological profile of 390 patients diagnosed with CRC who underwent surgical resection, over a six-year period, in the state of Paraíba, northeastern Brazil. Results Adenocarcinomas accounted for 98% of the cases of primary colorectal tumors, and 53.8% occurred in female patients. The average age of the sample was 63.5 years, with 81.8% of individuals older than 50 years of age and 6.4% under 40 years of age. The most frequent location was the distal colon; pT3 status was found in 71% of patients, and pT4 status, in 14.4%. Angiolymphatic and lymph-node involvements were found in 48.7% and 46.9% of the cases respectively. Distant metastasis was observed in 9.2% of the patients. Advanced disease was diagnosed in almost half of the patients (48.1%). The women in the sample had poorly-differentiated adenocarcinomas (p = 0.043). Patients under 60 years of age had a higher rate of lymph-node metastasis (p = 0.044). Tumor budding was present in 27.2% of the cases, and it was associated with the female gender, the mucinous histological type, and the depth of invasion (pT3 and pT4). Conclusions We conclude that the diagnosis of advanced disease in CRC is still a reality, with a high occurrence of aggressive prognostic factors, which results in a worse prognosis.

Clinicopathological characteristics of SMARCB1(INI1)-deficient sinonasal carcinoma

Objective: To investigate the clinicopathological characteristics, diagnosis, differential diagnosis and prognostic factors of SMARCB1 (INI1)-deficient sinonasal carcinoma (SDSC). Methods: Sixteen cases of SDSC diagnosed in the Department of Pathology, Beijing Tongren Hospital from January 2016 to September 2020 were enrolled. Ninety-nine cases of small round cell malignant tumors of the head and neck were selected as the control, including poorly-differentiated squamous cell carcinoma (n=10), poorly-differentiated adenocarcinoma (n=5), undifferentiated carcinoma (SNUC, n=4), NUT carcinoma (n=5), neuroendocrine carcinoma (n=10), and other non-epithelial tumors [olfactory neuroblastoma (n=10), rhabdomyosarcoma (n=10), NK/T-cell lymphoma (n=10), malignant melanoma (n=10), Ewing's sarcoma/primitive neuroectodermal tumor (EWS/PNET, n=5)] and non-keratinizing undifferentiated nasopharyngeal carcinoma (n=20). The clinical and pathologic characteristics of SDSC, and immunohistochemical (IHC) expression of broad-spectrum CKpan, CK7, CK8/18, CK5/6, p63, p40, p16, INI1, NUT and neuroendocrine markers (Syn, CgA, CD56) were evaluated. In situ hybridization (ISH) was used to detect EBER and fluorescence in situ hybridization (FISH) to detect INI1 gene deletion. Results: The 16 cases of SDSC accounted for 1.3% (16/1 218) of all malignant sinonasal tumors in the author's unit during this time period, and 2.4% (16/657) of all malignant epithelial tumors. Microscopically, there was no clear squamous and adenomatous differentiation, but "rhabdoid-like" cells, are often seen. All SDSC cases were positive for CKpan and CK8/18, negative for INI1; Epstein-Barr virus was not detected by ISH; and INI1 gene deletion was observed in all 11 SDSC patients with FISH. Twelve cases were followed up for 3-47 months. One died of tumor-related diseases half a year after diagnosis, and the remaining patients were alive with tumor, the longest survival time was 47 months. Conclusion: SDSC should be differentiated from a variety of poorly-differentiated tumors in the sinonasal area. Histologically, SDSC has no clear differentiation, but the tumor cells are characteristically basal-like or rhabdoid-like, with non-specific vacuoles, translucent or vacuolar nuclei, prominent nucleoli and necrotic foci. They are negative for INI1 IHC staining, and FISH demonstrates INI1 gene deletion. The clinical prognosis is still unclear, further studies on its biologic behavior and treatment methods are warranted.

S2891 Mistletoe Extract-Induced Liver Injury

Introduction: Herein we present an unusual case of a patient who presented with liver injury induced by herbal extract containing mistletoe. Case Description/Methods: A 33 year old woman with history of Crohn’s disease and adenocarcinoma of colon with metastasis to right ovary, fallopian tube, and bladder presented with two week history of right upper quadrant abdominal pain, jaundice, and scleral icterus. Labs were significant for total bilirubin 9.9 mg/dL, direct bilirubin 7.3 mg/dL, ALT 183 U/L, AST 136 U/L, and alkaline phosphatase 315 U/L. CT abdomen pelvis with IV contrast demonstrated large amount of retained stool throughout large bowel, sigmoid wall thickening, stable hepatic metastatic disease, and stable splenic lesions. Patient reported using a seven-day course of mistletoe extract in injection form several weeks prior to presentation to assist with boosting her immune system in setting of malignancy. Chronic liver work-up was largely unremarkable. Liver biopsy revealed poorly-differentiated adenocarcinoma but patient was known to have hepatic metastatic disease. There was a plan to repeat biopsy of normal appearing liver if bilirubin and transaminases remained elevated. However, at time of discharge, her total bilirubin improved to 7.6 mg/dL and transaminases normalized to ALT 18 U/L and AST 19 U/L. Patient was scheduled to be seen in clinic and is awaiting follow up. Discussion: Mistletoe extract has been thought to improve quality of life and boost the immune system in cancer patients. However, there has not been enough scientific research to substantiate these claims. In this patient, work up for the underlying etiology of her elevated transaminases and hyperbilirubinemia was largely unremarkable. As such, liver injury induced by herbal extract containing mistletoe was suspected. Patients taking herbal extracts should be advised of the risk of liver injury.

Retraction Note: Urachal tumour: case report of a poorly understood carcinoma

Urachal carcinoma is an uncommon neoplasm associated with poor prognosis. A 45-year-old man was admitted with complaints of abdominal pain and pollakisuria. A soft mass was palpable under his navel. TC-scan revealed a 11 × 6 cm tumor, which was composed of a cystic lesion arising from the urachus and a solid mass component at the urinary bladder dome. The tumor was removed surgically. Histological examination detected poor-differentiated adenocarcinoma, which had invaded the urinary bladder. The patient has been followed up without recurrence for 6 months. The urachus is the embryological remnant of urogenital sinus and allantois. Involution usually happens before birth and urachus is present as a median umbilical ligament. The pathogenesis of urachal tumours is not fully understood. Surgery is the treatment of choice and role of adjuvant treatment is not clearly understood.

Long-term outcomes of endoscopic resection followed by additional surgery after non-curative resection in undifferentiated-type early gastric cancer: a nationwide multi-center study.

Undifferentiated-type early gastric cancer (UD EGC) shows lower curative resection rates after endoscopic submucosal dissection (ESD). Additional surgery is recommended after non-curative resection. We evaluated the long-term outcomes of ESD followed by additional surgery after non-curative resection in UD EGC compared to those for surgery as initial treatment. We reviewed 1139 UD EGC patients who underwent ESD at 18 hospitals and 1956 patients who underwent surgery at two hospitals between February 2005 and May 2015. We enrolled 636 patients with non-curative ESD and 1429 surgery subjects beyond the curative ESD criteria. Among them, 133 patients with additional surgery after ESD (ESD + OP group) and 252 patients without additional surgery (ESD-only group) were matched 1:1 using propensity scores to patients with surgery as initial treatment (surgery group). Overall survival (OS) and recurrence-free survival (RFS) were compared. Signet ring cell carcinoma and poorly differentiated adenocarcinoma (PDA) were observed in 939 and 1126 cases, respectively. OS was significantly longer in the surgery group than in the ESD + OP group, especially for PDA. However, RFS was shorter in the ESD-only group than those in the ESD + OP and surgery groups. RFS did not differ significantly between the ESD + OP and surgery groups. Compared to the surgery group, the ESD-only and ESD + OP groups had an overall hazard ratio for RFS of 3.58 (95% confidence interval 1.44-8.88) and 0.46 (0.10-2.20), respectively. ESD followed by additional surgery after non-curative resection showed comparable cancer-specific outcomes to initial surgery in UD EGC.

Tumour Versus Germline BRCA Testing in Ovarian Cancer: A Single-Site Institution Experience in the United Kingdom.

The aim of this audit was to evaluate the usefulness and serviceability of testing for pathogenic mutations in BRCA1 or BRCA2 (BRCA1/2) genes in ovarian cancer (OC) patients. One hundred and thirty-five patients with more common histological sub-types of OC were retrospectively identified between 2011 and 2019. The fail rate of the molecular analysis was 7.4% (10/135). One hundred and twenty-five records were evaluated: 99 (79.2%) patients had wild-type BRCA (both somatic and germline); tumour BRCA1/2 (tBRCA1/2) pathogenic mutations were found in 20 (16%) patients with distribution between BRCA1 and BRCA2 being 40% and 60%, respectively; 13 (10.4%) patients with pathogenic variants had germline mutations; and tBRCA1/2 with variant of unknown significance (VUS), in the absence of pathogenic BRCA1 or BRCA2 variants, was detected in 6 (4.8%) patients. Our data show that expanding the molecular service to the routine first-tumour testing for patients with OC will potentially increase the detection rate of BRCA mutations, thereby providing early benefits of PARP inhibitors therapy. The tumour testing service should continue to be offered to newly diagnosed patients with high-grade epithelial cancers, including high-grade serous carcinoma, but also with carcinosarcomas and poorly-differentiated metastatic adenocarcinomas of unknown origin.