Undifferentiated Adenocarcinoma Research Articles

Accuracy of the preoperative estimation of esophageal invasion length of adenocarcinoma of the esophagogastric junction and its discrepancy with the pathological measurement.

The incidence of esophagogastric junction (EGJ) adenocarcinoma has increased worldwide. As the EGJ is located at the boundary between the thoracic and abdominal cavities, the optimal surgical approach is a subject of debate and estimation of the esophageal invasion length (EIL) is an important factor in its selection. Data from our in-house database were extracted for consecutive patients with Siewert type I, II and III EGJ adenocarcinoma (EIL ≤ 4cm), who underwent transhiatal or transthoracic surgical resection between 2010 and 2016. The clinical records of these patients were reviewed and the accuracy of EIL estimation and its discrepancy with the pathological measurement were analyzed. A total of 82 patients were included in the final analysis. We established that EIL was underestimated in 49 of these patients (59.8%). The mean-distance discrepancy between the preoperative and pathological diagnosis of EIL in the underestimation group was 7.0mm. Multivariate analysis revealed that submucosal cancer spread was an independent risk factor for underestimation (P < 0.01). The mean length of submucosal cancer spread was longer for undifferentiated histologic type EGJ adenocarcinomas. (P < 0.01). The EIL was underestimated in approximately 60% of EGJ adenocarcinomas requiring surgical treatment. Thus, careful management is necessary, especially for EGJ adenocarcinoma of the undifferentiated histologic type.

Sarcomatoid carcinoma of the pancreas (Review).

Sarcomatoid carcinoma of the pancreas (SCP) is a rare and aggressive subtype of undifferentiated pancreatic ductal adenocarcinoma, with a generally poor prognosis and only sporadic cases reported worldwide. Histologically, the most notable feature of SCP is the presence of abundant of mesenchymatoid spindle tumor cells in the tumor, which lack glandular differentiation. Immunohistochemically, SCP is characterized by the expression of both mesenchymal and epithelial markers. With only a few reported cases, there is limited knowledge about its molecular and clinicopathological characteristics. Therefore, the present study performed a literature search to identify all relevant published studies. The present review provides an overview of the histogenesis, diagnosis, genetic features, prognosis and treatment of SCP, specifically focusing on the molecular alterations. Furthermore, a single-center experience is reported, which adds to the limited evidence available in the literature.

Pathological findings and differential diagnoses of lymph node diseases in slaughtered cattle in Brazil: A study of 2000 samples.

Slaughterhouse inspections play a crucial role in the sanitary control of zoonoses and foodborne diseases. This study aimed to identify and analyze the frequencies of lymph node diseases in cattle slaughtered for human consumption, using the samples sent to the anatomic pathology service of the Federal Laboratory for Agricultural Defense (Laboratório Federal de Defesa Agropecuária), Minas Gerais, Brazil, from January 2015 to September 2022. In total, 2000 lymph node samples were analyzed, and additional information was individually retrieved. Lesions were most frequently identified in thoracic lymph nodes. Bacterial isolation and quantitative polymerase chain reaction (qPCR) were performed using samples suspected of tuberculosis. Tuberculosis cases accounted for 89.3% of the samples. Histopathology was more sensitive than other ancillary tests for diagnosing tuberculosis. Paraffin-embedded tissues from lymphoma cases were subjected to immunophenotyping using anti-CD3 and anti-CD79a immunohistochemistry. Frozen and/or paraffin-embedded tissues from lymphoma cases were used to identify the enzootic bovine leukosis (EBL) retrovirus through qPCR. Other diagnoses included primary (T- and B-cell lymphoma) and metastatic neoplasms (squamous cell carcinoma, pulmonary adenocarcinoma, undifferentiated carcinoma, undifferentiated adenocarcinoma, undifferentiated sarcoma, undifferentiated round cell tumor, mesothelioma, hepatic carcinoid, meningioma, and seminoma), actinogranulomas (pyogranulomatous lymphadenitis [actinobacillosis and actinomycosis]), idiopathic lymphadenitis (neutrophilic and/or histiocytic, granulomatous, and suppurative), and miscellaneous nonspecific lymphadenopathies (depletion/lymphoid atrophy, lymphangiectasia, erythrocyte drainage, parasitic eosinophilic lymphadenitis, follicular hyperplasia, and toxic granulomatous lymphadenitis). The combination of histopathology with complementary techniques is important for successful diagnosis, especially in complex cases of high epidemiological, economic, and zoosanitary importance, such as tuberculosis and EBL.

Non-improvement of atrophic gastritis in cases of gastric cancer after successful Helicobacter pylori eradication therapy.

Helicobacter pylori (H. pylori) infection is closely related to the development of gastric cancer (GC). However, GC can develop even after H. pylori eradication. Therefore, it would be extremely useful if GC could be predicted after eradication. The Kyoto classification score for gastritis (GA) is closely related to cancer risk. However, how the score for GC changes after eradication before onset is not well understood. To investigate the characteristics of the progression of Kyoto classification scores for GC after H. pylori eradication. Eradication of H. pylori was confirmed in all patients using either the urea breath test or the stool antigen test. The Kyoto classification score of GC patients was evaluated by endoscopy at the time of event onset and three years earlier. In addition, the modified atrophy score was evaluated and compared between the GC group and the control GA group. In total, 30 cases of early GC and 30 cases of chronic GA were evaluated. The pathology of the cancer cases was differentiated adenocarcinoma, except for one case of undifferentiated adenocarcinoma. The total score of the Kyoto classification was significantly higher in the GC group both at the time of cancer onset and three years earlier (4.97 vs 3.73, P = 0.0034; 4.2 vs 3.1, P = 0.0035, respectively). The modified atrophy score was significantly higher in the GC group both at the time of cancer onset and three years earlier and was significantly improved only in the GA group (5.3 vs 5.3, P = 0.5; 3.73 vs 3.1, P = 0.0475, respectively). The course of the modified atrophy score is useful for predicting the onset of GC after eradication. Patients with severe atrophy after H. pylori eradication require careful monitoring.

Dysbiosis in gastric mucosal microbiota associated with gastric carcinogenesis.

381 Background: Gastric microbiota, including H. pylori, may play a role in the development of gastric cancer. This study aimed to investigate the gastric microbiota throughout the stages of gastric carcinogenesis, encompassing atrophic gastritis, gastric dysplasia, and gastric adenocarcinoma. Methods: From December 2021 to August 2023, we collected gastric mucosal tissue samples from patients with atrophic gastritis, gastric dysplasia, and early gastric cancer. Subsequently, we conducted 16S rRNA gene profiling through next-generation sequencing. We compared alpha-diversity and beta-diversity within each group and analyzed the taxonomic composition. Results: This study included a total of 98 patients, comprising 16 with atrophic gastritis, 23 with low-grade dysplasia, 15 with high-grade dysplasia, and 44 with early gastric cancer. The H. pylori infection status was comparable across all groups. While there was a difference in alpha diversity between tumor lesions and normal stomach lesions, it did not reach statistical significance. Notably, Phyllobacterium was dominant in early gastric cancer, Prevotella in high-grade dysplasia, and Kocura in low-grade dysplasia. Furthermore, within the early gastric cancer group, Bacillus was widely distributed in cases of undifferentiated type adenocarcinoma. Conclusions: The analysis of microbiota collected from Korean stomach tissue revealed distinct microbial distributions across the various stages of gastric carcinogenesis.

Comprehensive analysis of cancer of unknown primary and recommendation of a histological and immunohistochemical diagnostic strategy from China

BackgroundPrevious studies on cancer of unknown primary (CUP) mainly focus on treatment and prognosis in western populations and lacked clinical evaluation of different IHC markers, so this study aimed to evaluate characteristics of CUP and recommend a diagnostic strategy from a single center in China.Methods and resultsData of 625 patients with CUP were retrospectively collected and reviewed. The patients ranged in age from 20 to 91 years, with a female-to-male ratio of 1.3:1. The predominant histological type was poor or undifferentiated adenocarcinomas (308; 49.3%). The results of Canhelp-Origin molecular testing for the identification of the tissue of origin in 262 of 369 patients (71.0%) were considered predictable (similarity score > 45), with the most common predicted primary tumor site being the breast (57, 21.8%). Unpredictable molecular results correlated with more aggressive clinical parameters and poor survival. Thee positivity rates of several targeted antibodies (GATA3, GCDFP15, TTF1, Napsin A, and PAX8), based on the clinically predicted site, were lower than those reported for the corresponding primary tumors. Nonetheless, TRPS1 and INSM1 were reliable markers of predicted breast carcinoma (75.0%) and neuroendocrine tumors (83.3%), respectively. P16 expression, as well as HPV and EBER testing contributed significantly to the diagnosis of squamous cell carcinomas. Survival analysis revealed that older ages (> 57), ≥ 3 metastatic sites, non-squamous cell carcinomas, bone/liver/lung metastases, unpredictable molecular results, and palliative treatment correlated with poor overall survival.ConclusionsWe recommend a CUP diagnostic strategy involving the use of targeted antibody panels as per histological findings that is potentially applicable in clinical practice. The markers TRPS1, INSM1, and P16 expression, as well as HPV and EBER testing are particularly valuable in this aspect. Molecular testing is also predictive of survival rates.

Early onset, development and histological features of gastric signet-ring cell carcinoma.

To explore the early onset, development and histological features of gastric signet-ring cell carcinoma (SRCC). Three hundred and sixty-two patients with differentiated adenocarcinoma with signet-ring cells were enrolled. Histomorphological and immunohistochemical features and patterns of the specimens were observed in detail. Infection of the gastric mucosa, especially by Helicobacter pylori, can cause massive cell proliferation and transformation in the deep gastric foveola, the isthmus of the gastric gland, and the proliferative zone of the upper neck of the gland. Signet-ring-like heterocysts monoclonally proliferated after the redifferentiation and reproliferation, extending horizontally along the gastric foveola. Gastric foveolar-type SRCC grew infiltratively into the lamina propria of the mucosa and the submucosa, signet-ring cells could differentiate into undifferentiated adenocarcinoma with signet-ring cell differentiation, mucinous adenocarcinoma with signet-ring cell differentiation, gastric adenocarcinoma with signet-ring cell differentiation, and fundus gland adenocarcinoma with signet-ring cell differentiation. Early SRCC developed from the proliferative zones of the fundus of the gastric foveola and the neck of the gastric gland, growing horizontally along the gastric foveola. It developed into gastric adenocarcinoma with signet-ring cell differentiation after reproliferation and retransformation in the mucosa.

A Retrospective Multicenter Study of the Clinicopathological Characteristics and Prognosis of Young Adult Patients with Colorectal Cancer: Effects of Chemotherapy on Prognosis.

The objective of this study was to evaluate clinicopathologic features of young patients with colorectal cancer (CRC) and to compare their prognosis with those of older patients Methods: We retrospectively reviewed the medical records of patients who underwent surgery for stage 0-III CRC at four university-affiliated hospitals between January 2011 and December 2020. The patients were divided into two groups, the young adult group (≤45 years) and the older group (>45 years). Of 1992 patients, 93 (4.6%) were young adults and 1899 (95.3%) were older patients. Young patients showed more symptoms (p = 0.014) and more poorly or undifferentiated adenocarcinoma (p = 0.047) than older patients. The young adult patients were more likely to receive adjuvant chemotherapy (p < 0.001) and multidrug agents (p = 0.029), and less likely to cease chemotherapy (p = 0.037). The five-year RFS (recurrence-free survival) rate was better in the young adults than in the older patients (p = 0.009). In the multivariable analysis, young age was a significant prognostic factor for better RFS (p = 0.015). Young patients with CRC had more symptoms, aggressive histological features than older patients. They received more multidrug agents and discontinued chemotherapy less often, resulting in better prognosis.

Local Recurrence after Endoscopic Submucosal Dissection of Early Gastric Cancer

Endoscopic submucosal dissection (ESD) is considered the treatment of choice for early gastric cancer (EGC) with a negligible risk of lymph node metastasis. Locally recurrent lesions on artificial ulcer scars are difficult to manage. Predicting the risk of local recurrence after ESD is important to manage and prevent the event. We aimed to elucidate the risk factors associated with local recurrence after ESD of EGC. Between November 2008 and February 2016, consecutive patients (n = 641; mean age, 69.3 ± 9.5 years; men, 77.2%) with EGC who underwent ESD at a single tertiary referral hospital were retrospectively analyzed to evaluate the incidence and factors associated with local recurrence. Local recurrence was defined as the development of neoplastic lesions at or adjacent to the site of the post-ESD scar. En bloc and complete resection rates were 97.8% and 93.6%, respectively. The local recurrence rate after ESD was 3.1%. The mean follow-up period after ESD was 50.7 ± 32.5 months. One case of gastric cancer-related death (0.15%) was noted, wherein the patient had refused additive surgical resection after ESD for EGC with lymphatic and deep submucosal invasion. Lesion size ≥15 mm, incomplete histologic resection, undifferentiated adenocarcinoma, scar, and the absence of erythema of the surface were associated with a higher risk of local recurrence. Predicting local recurrence during regular endoscopic surveillance after ESD is important, especially in patients with a larger lesion size (≥15 mm), incomplete histologic resection, surface changes of scars, and no erythema of the surface.

P-166 Local recurrence after endoscopic submucosal dissection of early gastric cancer

Endoscopic submucosal dissection (ESD) is considered the treatment of choice for early gastric cancer (EGC) with a negligible risk of lymph node metastasis. However, locally recurrent lesions on artificial ulcer scars are difficult to manage. Therefore, predicting the risk of local recurrence after ESD is important to manage and prevent the event. This study aimed to elucidate risk factors associated with local recurrence after ESD of EGC. Between November 2008 and February 2016, consecutive patients (n=641; mean age, 69.3±9.5 years; men, 77.2%) with EGC who underwent ESD at a single tertiary referral hospital were retrospectively analyzed to evaluate the incidence and factors associated with local recurrence. Local recurrence was defined as the development of neoplastic lesions at or adjacent to the site of the post-ESD scar. En bloc and complete resection rates were 97.8% and 93.6%, respectively. The local recurrence rate after ESD was 3.1%. The mean follow-up period after ESD was 50.7±32.5 months. One case of gastric cancer-related death (0.15%) was noted, wherein the patient had refused additive surgical resection after ESD for EGC with lymphatic and deep submucosal invasion. Lesion size ≥15 mm, incomplete histologic resection, undifferentiated adenocarcinoma, scar, and absence of erythema of the surface were associated with a higher risk of local recurrence. Predicting local recurrence during regular endoscopic surveillance after ESD is important, especially in patients with a larger lesion size (≥15 mm), incomplete histologic resection, surface changes of scars, and no erythema of the surface.

A RARE CASE STUDY OF MEDULLARY CARCINOMA OF DESCENDING COLON REPORTED ON HISTOPATHOLOGY

Medullary carcinoma (MC) of the colon is a rare and unique histologic subtype of colorectal cancer whichcharacterized by poor glandular differentiation and intraepithelial lymphocytic infiltrate. This has now been incorporated as a separate entity in the World Health Organization (WHO) classification of colorectal cancers.It is commonly associated with deficient mismatch repair proteins and has a strong association with Lynch syndrome. Diagnosis is challenging as it does not have the usual immunohistochemical stains on pathology seen in colorectal adenocarcinoma. Here, we discuss an interesting case of MC of the colon that was metastatic on presentation and constituted a diagnostic challenge1.&#x0D; Keywords: medullary carcinoma, colorectal carcinomas (CRC), medullary carcinoma of colon,poorly differentiated adenocarcinoma, undifferentiated adenocarcinoma.

Role of Ultrasound-Guided Tru-cut Biopsy in the Diagnosis of Peripheral Lung and Pleural Lesions

Abstract Background Transthoracic needle biopsy is a well-established technique for diagnosing pulmonary lesions. Computed tomography (CT) is usually used as guidance. Ultrasound (US)-guided biopsy is a relatively affordable modality for diagnosis of peripheral lung lesions (PLLs; also known as peripheral pulmonary lesions [PPLs]) and peripheral pleural lesions. Objectives The purpose of this study was to study the diagnostic yield of US guidance sampling a consecutive series of peripheral lung and pleural lesions and potential factors influencing the diagnostic yield with recording the occurrence of any complications. Patients and Methods This was a prospective study that was conducted at Ain Shams University Hospitals upon a population of 60 patients, during the period from September 2018 to August 2019. A special puncture transducer is used to perform US-guided biopsy with visualization of the biopsy needle and the lesion; facilitating the sampling procedure. Results The use of US-guided transthoracic needle biopsies across 60 patients was shown to have a yield of 75% which found the occurrence of 45 conclusive and 15 non-conclusive results From this study population, 70% (n = 42/45) were found to have malignant manifestations, of which 26 were undifferentiated high grade adenocarcinoma, and 9 were moderately differentiated adenocarcinoma. As for complications arising from the biopsy procedure, twenty percent 20% (n = 12) of patients suffered from complications in the form of hemoptysis in 8 which was controlled by hemostatic measures and 4 patients acquired pneumothorax, three (¾) of them received high flow oxygen and conservative treatment and only one (1/4) patient had intercostal tube placement. Diagnostic yield was significantly increased with the presence of Wedge shaped hypoechoic lesions(p &amp;lt; 0.001), hard Mass consistency was significantly highly associated with conclusive results (p &amp;lt; 0.001), as well as a significant link between the longitudinal diameter of masses that had a mean length of 45.05mm ±12.93mm (#x0003D; 0.029).It also showed that more biopsies taken were highly significant correlation with conclusive outcomes (p &amp;lt; 0.001). Conclusion US-guided biopsy is a robust and accurate procedure to effectively diagnose peripheral lung lesions, with a low incidence of complications and gradually improving results with the mastery of the procedure.

Neoadjuvant PD-1 Inhibitors and Chemotherapy for Locally Advanced NSCLC: A Retrospective Study

BackgroundStage III non-small cell lung cancer (NSCLC) encompasses a variety of local invasion and nodal involvement and its management is still under debate. Immune checkpoint inhibitors (ICIs) have been shown to improve the survival in metastatic NSCLC, but are far from being accepted as an induction therapy. MethodsWe retrospectively collected data of all patients who received induction ICIs (nivolumab or pembrolizumab) and chemotherapy (carboplatin with paclitaxel) for stage IIIA-B NSCLC followed by surgery in our unit between January 2019 and March 2020. ResultsOf the 12 patients (9 men, 3 women) 6 had a squamous cell carcinoma, 4 had adenocarcinoma, 1 had an undifferentiated adenocarcinoma, and 1 had adeno-squamous carcinoma. Seven patients had stage IIIA disease and 5 had stage IIIB. After induction therapy, 6 patients had stable disease and 6 had a partial response. The median tumor reduction was 3.05 cm (range, 2.30-8.70 cm). All patients, but 1 due to the COVID-19 outbreak, had no delay in surgery. Two patients experienced myelosuppression after induction therapy, 2 had minor adverse effects. Three patients had postoperative complications not related to the induction therapy. All patients had a pathologic response: 5 complete, 4 major, and 3 partial. Eleven patients are alive (mean follow-up, 18.17 ± 4.97 months) and free of disease. ConclusionsInduction ICI chemotherapy may be a valid treatment in patients with locally advanced NSCLC, providing important tumor downstaging and rendering patients operable. In our experience patients had few side effects and a good pathologic response.

Neutrophil-to-Lymphocyte Ratio Is a Useful Marker for Predicting Histological Types of Early Gastric Cancer.

Background: The indications for endoscopic submucosal dissection (ESD) for gastric cancer are based on preoperative histological assessment; however, examination of tissue biopsy is not always reliable as only a limited portion of the lesion can be obtained. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are markers of inflammatory response and are potentially associated with the grade of malignancy in gastric cancer. We aimed to investigate the association between NLR and PLR and the histology of gastric cancer. Methods: This study included 218 patients who underwent ESD for gastric cancer. The relationship between NLR/PLR and histological diagnosis was investigated. Results: Patients with adenocarcinomas showed significantly higher NLR and PLR than those with adenomas (p < 0.001 and p < 0.05, respectively). Further, patients with undifferentiated adenocarcinoma showed a significantly higher NLR (p < 0.05) than those with differentiated adenocarcinoma. Conclusion: This study suggests that NLR could be a useful marker for assessing early gastric cancer.

Sarcomatoid Carcinoma of the Transverse Colon With Extremely Aggressive Brain Metastases

Introduction Sarcomatoid carcinoma (SC) is a rare subtype of malignant neoplasm with a poor prognosis that involves both carcinomatous and sarcomatous components. Although it may develop in various organs, SC in the large intestine has rarely been reported. It is not rare for patients with SC to have distant metastasis, reflecting its highly aggressive oncologic features, but cases with brain metastasis on initial visit are rare. In this report, we described a case of SC in the transverse colon with brain metastases whose initial symptom was neurological disorder, and reviewed 31 reported cases of SC. Case presentation A 70-year-old man was admitted to our hospital with the chief complaints of gait disorder and severe dizziness. Head magnetic resonance imaging revealed tumor masses in the anterior lobe and cerebellum. A large tumor in the transverse colon was detected by colonoscopy and abdominal enhanced computed tomography (CT), and was diagnosed as undifferentiated adenocarcinoma by histology. Laparoscopic extended right hemicolectomy was performed to remove the obstruction, and the resected specimens revealed an invasive tumor consisting of a mixture of carcinomatous and sarcomatous components. According to the immunopathological study, the patient was diagnosed with SC. The clinical course was extremely aggressive, and the patient died on the 28th postoperative day because of disease progression. Conclusion To the best of our knowledge, this is the first case of SC in the transverse colon with a neurological disorder derived from brain metastases. This experience may contribute to the guidance regarding proper therapeutic options for SC.

Linking Epigenetics, Metabolism and Cancer: Lessons From SIRT6

In recent years, chromatin regulators have emerged as key modulators in cancer. We discovered that the mammalian histone deacetylase SIRT6 is a key chromatin factor, modulating expression of metabolic, developmental, and ribosomal protein genes. In recent studies, we identified a loss of function mutation in SIRT6 behind a human syndrome of perinatal lethality. In the context of cancer, we found SIRT6 to act as a robust tumor suppressor, by modulating glucose metabolism. As Otto Warburg described decades ago, cancer cells exhibit glycolytic metabolism, where pyruvate, instead of contributing to ATP production in the mitochondria, is converted to lactate even under normoxia conditions. We found SIRT6 as the first chromatin factor in charge of suppressing the Warburg effect in colon and skin cancer. At the cellular level, SIRT6 inactivation leads to increased cellular glucose uptake, higher lactate production and decreased mitochondrial activity. Our results indicate that SIRT6 directly regulates expression of several key glycolytic and ribosomal genes, co-repressing Hif1a and Myc, respectively, and acting as a histone H3 lysine9 (H3K9) and lysine 56 (H3K56) deacetylase. Notably, we recently identified SIRT6 as the first deacetylase to specifically inhibit transcriptional elongation, rather than initiation, in its targets. Strikingly, we determined in new studies that such glycolytic switch provides an advantage even at the early initiating cancer stem cells stage, in what we identified as the cell-of-origin for the Warburg effect. In addition, we found SIRT6 to act as a robust tumor suppressor in the context of pancreatic cancer. However, in this case, SIRT6 did not influence metabolism, but rather silenced expression of the developmental gene Lin28b, in this way protecting against aggressive undifferentiated pancreatic adenocarcinoma. Our studies highlight the important role epigenetic factors, such as SIRT6, play in protecting against tumor progression by providing “epigenetic plasticity”, inhibiting adaptive responses in transformed cells.

S1656 Not Your Standard Adenocarcinoma, a Case of Medullary Carcinoma of the Colon

INTRODUCTION: Adenocarcinoma of the colon is the most common type of colon cancer. Medullary carcinoma (MC) of the colon is a rare histological subtype of adenocarcinoma. MC has been described to have specific histopathological features but can still be difficult to distinguish from poorly differentiated adenocarcinoma. We aim in this case report to shed light on this rare subtype of colon cancer and describe its histopathological features. CASE DESCRIPTION/METHODS: 76-year-old male presented to our hospital reporting 3 months of back pain, fatigue, and 10lb weight loss. Past medical history significant for atrial fibrillation and history of renal cell carcinoma. CT abdomen/pelvis showed a necrotic mass within the ascending colon suggestive of colon cancer. Metastatic lymph nodes were also suspected on the scan. Subsequent colonoscopy showed a large mass at the hepatic flexure. Multiple biopsies were taken from mass. Histopathologic sections showed sheets of malignant epithelial cells extending from the submucosa into the lamina propria. Immunohistochemical staining demonstrated that the malignant cells were positive for pan-cytokeratin, but negative for CK20, CDX2, S-100, CD45, synaptophysin, chromogranin, and PSA. These initial findings were consistent with invasive poorly differentiated carcinoma. Further immunohistochemical testing was done and showed mismatch repair deficiency with loss of MLH1 and PMS2 consistent with medullary carcinoma of the colon, which typically shows aberrant loss of CK20 and CDX2 (typical markers of colorectal adenocarcinoma). Due to patients advanced disease (stage IV), decision made to start palliative chemotherapy with Xeloda + Oxaliplatin + Avastin. Patient passed away approximately three months after initial diagnosis. DISCUSSION: MC of the colon is extremely rare with limited clinical and epidemiologic data. Based on population-based analysis, medullary carcinoma makes up 5-8 cases for every 10,000 colon cancers diagnosed. Most patients are diagnosed earlier in the disease course and metastatic disease is seen in 10% of patients at time of diagnosis. Immunohistochemical analysis is essential to differentiate from poorly-differentiated and undifferentiated colon adenocarcinomas. Classic findings include loss of staining for MLH-1 and CDX-2. In the current published data, overall prognosis of MC is favorable when compared to poorly differentiated or undifferentiated adenocarcinomas. However, data is limited regarding available treatment strategies and response.Figure 1

Osteolysis of the Carpus as a Presentation of Pancoast's Tumor

Lung cancer is most often located in the right upper lobe and is called a Pancoast tumor. On many occasions, the Pancoast tumor begins with osteomyoarticular manifestations. A 72-year-old white male patient of peasant origin is presented who attends the Guard Corps because for a few weeks an increase in volume has been noted on the back of the right hand accompanied by pain in the absence of trauma. An X-ray of the hand was performed, observing osteolysis of the carpal bones, in the preoperative preparation a chest X-ray was performed where an image of condensation of the upper lobe of the right lung was observed. An excisional biopsy of the carpal lesion was performed, the result of which was metastasis of highly undifferentiated lung adenocarcinoma.

Diagnostic limitations of magnifying endoscopy with narrow-band imaging in early gastric cancer

Background and study aims Magnifying endoscopy with narrow band imaging (M-NBI) has made a huge contribution to endoscopic diagnosis of early gastric cancer (EGC). However, we sometimes encountered false-negative cases with M-NBI diagnosis (i. e., M-NBI diagnostic limitation lesion: M-NBI-DLL). However, clinicopathological features of M-NBI-DLLs have not been well elucidated. We aimed to clarify the clinicopathological features and histological reasons of M-NBI-DLLs. Patients and methods In this single-center retrospective study, M-NBI-DLLs were extracted from 456 EGCs resected endoscopically at our hospital. We defined histological types of M-NBI-DLLs and analyzed clinicopathologically to clarify histological reasons of M-NBI-DLLs. Results Of 456 EGCs, 48 lesions (10.5 %) of M-NBI-DLLs were enrolled. M-NBI-DLLs was classified into four histological types as follows: gastric adenocarcinoma of fundic-gland type (GA-FG, n = 25), gastric adenocarcinoma of fundic-gland mucosal type (GA-FGM, n = 1), differentiated adenocarcinoma (n = 14), and undifferentiated adenocarcinoma (n = 8). Thirty-nine lesions of M-NBI-DLLs were H. pylori -negative gastric cancers (39/47, 82.9 %). Histological reasons for M-NBI-DLLs were as follows: 1) completely covered with non-neoplastic mucosa (25/25 GA-FG, 8/8 undifferentiated adenocarcinoma); 2) well-differentiated adenocarcinoma with low-grade atypia (1/1 GA-FGM, 14/14 differentiated adenocarcinoma); 3) similarity of surface structure (10/14 differentiated adenocarcinoma); and 4) partially covered and/or mixed with a non-neoplastic mucosa (1/1 GA-FGM, 6/14 differentiated adenocarcinoma). Conclusions Diagnostic limitations of M-NBI depend on four distinct histological characteristics. For accurate diagnosis of M-NBI-DLLs, it may be necessary to fully understand endoscopic features of these lesions using white light imaging and M-NBI based on these histological characteristics and to take a precise biopsy.

Abstract 2337: Pan-cancer analysis of sex differences and their associations with ancestry and genomic biomarkers in a large comprehensive genomic profiling dataset

Abstract Background: Sex differences in the prevalence of cancer subtypes can inform patient screening, diagnosis, and treatment, but for many disease ontologies (DO), sex disparities have not been fully explored, especially with regards to ancestral and genomic subsets. Furthermore, existing data and reports may lack centralized expert pathology review or comprehensive genomic profiling (CGP) that can enable better characterization of biological and environmental etiologies. Design: The cohort consisted of 276,696 de-identified patient cancers, 45.7% male and 54.3% female, submitted to Foundation Medicine for CGP. Each patient was assigned an ancestry of either African, admixed American, East Asian, European, or South Asian, using a SNP-based machine learning methodology (J. Newberg et al., AACR 2019). Within the dataset 321 DOs originate at a known tissue site of origin common to both sexes. Binomial testing for significance of expected (50%) versus observed ratio of the sexes was performed for each DO, with correction for multiple hypothesis testing. For each DO, Fisher's exact tests were used to identify associations between ancestry and sex and associations between sex and gene-level genomic biomarkers (including the detection of a viral-derived gene) with ≥ 1% prevalence within the DO. Results: Of the 321 DOs, significant sex differences (corrected p-value ≤ 0.05) were seen in 106 DOs, of which 84 were significantly skewed towards males and 22 towards females. Among all DO and ancestry combinations, 14 DO-ancestry pairings showed a statistically significant (corrected p-value ≤ 0.05) skew towards one sex when compared to all other patients in the disease group. Notably, there was an enrichment of lung small cell undifferentiated carcinoma in East Asian men (OR = 2.75, corrected p-value = 0.027) and esophagus squamous cell carcinoma in East Asian men (OR = 2.55, corrected p-value = 0.028). 33 DOs exhibited sex biases in gene alterations (OR ≥ 2 and corrected p ≤ 0.05). Of particular note are a few genes that were highly enriched in a single sex across multiple distinct disease groups: CDKN2A/CDKN2B (bladder, anus, CNS non-glioma, and kidney diseases), TERT (hepato-biliary, kidney, and anus diseases), and ASXL1 (myelomas and plasma neoplasms) for males; ATRX in both lung small cell undifferentiated carcinoma and colon adenocarcinoma for females. Conclusions: Using FMI's large cancer cohort, significant differences in the occurrences of the sexes were observed in various DOs and have the potential to inform our understanding of different disease etiologies and possible courses of therapy. Further analyses incorporating covariates may help to explain the source of these imbalances. Citation Format: Benjamin G. Kaplan, Peter Halmos, Justin Y. Newberg, Ethan S. Sokol, Meagan Montesion, Lee A. Albacker, Vincent Miller, Jeff S. Ross, Garrett M. Frampton, Jonathon K. Killian. Pan-cancer analysis of sex differences and their associations with ancestry and genomic biomarkers in a large comprehensive genomic profiling dataset [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2337.