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Background The relationship between sarcopenia and the prognoses of patients with gastric neuroendocrine neoplasms (g-NENs) is unclear. This study was designed to explore the effects of sarcopenia on short-term and long-term outcomes of patients with g-NENs after radical gastrectomy. Methods This study retrospectively collected data from 138 patients with g-NENs after radical gastrectomy. The skeletal muscle index (SMI) diagnostic threshold for sarcopenia was determined using X-tile software. Cox regression analyses were performed to determine the independent risk factors for 3-year overall survival (OS) and 3-year recurrence-free survival (RFS). Results In this study, 59 patients (42.8%) were diagnosed with sarcopenia. Among patients in the sarcopenia group and nonsarcopenia group, the incidences of total postoperative complications were 33.9 and 30.4%, incidences of serious postoperative complications were 0 and 3.7%, incidences of postoperative surgical complications were 13.6 and 15.2%, and incidences of postoperative systemic complications were 20.3 and 15.2%, respectively (all p > 0.05). The 3-year OS and RFS rates were significantly worse in the sarcopenia group than in the nonsarcopenia group (OS: 42.37% vs 65.82%, p = 0.004; RFS: 52.54% vs 68.35%, p = 0.036). The multivariate analysis revealed a relation between sarcopenia and the long-term prognoses of patients with g-NENs. A stratified analysis based on the pathological type revealed that the Kaplan-Meier curve was only significantly different in patients with gastric mixed adenoneuroendocrine carcinoma (gMANEC) (OS: 40.00% vs 71.79%, p = 0.007; RFS: 51.43% vs 74.36%, p = 0.026); furthermore, the multivariate analysis identified sarcopenia as an independent risk factor for patients with gMANEC (p Conclusions Sarcopenia is not related to the short-term prognoses of patients with g-NENs. Sarcopenia is an independent risk factor for patients with gMANEC after radical surgery.

Key Points Question Are there any differences in prognoses or recurrence patterns associated with gastric neuroendocrine carcinoma, mixed adenoneuroendocrine carcinoma, or adenocarcinoma? Findings This cohort study included 3689 patients with resectable gastric adenocarcinoma, gastric neuroendocrine carcinoma, or gastric mixed adenoneuroendocrine carcinoma. Propensity score matching analysis found that, compared with gastric adenocarcinoma, gastric neuroendocrine carcinoma and gastric mixed adenoneuroendocrine carcinoma were independent risk factors associated with worse disease-free survival, postrecurrence survival, and distant recurrence outcomes. Meaning These findings suggest that different follow-up and treatment strategies should be developed to improve the long-term survival of patients with gastric neuroendocrine carcinoma or gastric mixed adenoneuroendocrine carcinoma, especially for patients with tumors penetrating into the subserosa or deeper layers and with lymph node metastasis., This cohort study examines differences in long-term survival and patterns of recurrence among patients with gastric neuroendocrine carcinoma, gastric mixed adenoneuroendocrine carcinoma, and gastric adenocarcinoma., Importance Gastric neuroendocrine carcinoma and mixed adenoneuroendocrine carcinoma are rare pathological types of gastric cancer, and there is a lack of multicenter studies comparing the prognosis and recurrence patterns of gastric neuroendocrine carcinoma, gastric mixed adenoneuroendocrine carcinoma, and gastric adenocarcinoma. Objective To compare the differences in long-term survival and patterns of recurrence among gastric neuroendocrine carcinoma, gastric mixed adenoneuroendocrine carcinoma, and gastric adenocarcinoma. Design, Setting, and Participants This cohort study included patients with resectable gastric neuroendocrine carcinoma and gastric mixed adenoneuroendocrine carcinoma at 23 hospitals in China from January 2006 to December 2016. In addition, patients with gastric adenocarcinoma were selected as controls. Propensity score–matched analysis was used to match pathological stage among the different pathological types, and disease-free survival (DFS), postrecurrence survival (PRS), and patterns of recurrence were examined. Data analysis was conducted from July 15, 2020, to October 21, 2020. Exposures Curative resection for gastric neuroendocrine carcinoma, gastric mixed adenoneuroendocrine carcinoma, and gastric adenocarcinoma. Main Outcomes and Measures The main outcomes were DFS and patterns of recurrence. Results A total of 3689 patients were analyzed (median [interquartile range] age, 62 [55-69] years; 2748 [74.5%] men), including 503 patients (13.6%) with gastric neuroendocrine carcinoma, 401 patients (10.9%) with gastric mixed adenoneuroendocrine carcinoma, and 2785 patients (75.5%) with gastric adenocarcinoma. After propensity score matching, 5-year DFS was 47.6% (95% CI, 42.7%-52.5%) for patients with gastric neuroendocrine carcinoma, compared with 57.6% (95% CI, 55.1%-60.1%) with gastric adenocarcinoma (P

Rationale: Gastric mixed adenoneuroendocrine carcinoma (gMANEC) is a rare malignant tumor. Most gMANECs are diagnosed at an advanced stage and have a worse prognosis than gastric adenocarcinoma. In order to improve the prognosis, it is necessary to diagnose gMANEC at an early stage. However, the endoscopic features of early gMANECs are unclear. We, herein, report a case of early gMANEC that showed characteristic magnifying endoscopic findings. Patient concerns: A 78-year-old man was referred to our institution for endoscopic resection of a gastric lesion. He had a medical history of distal gastrectomy due to early gastric cancer with negative surgical margins 9 years previously. Diagnosis: Esophagogastroduodenoscopy showed a reddish depressed lesion on the suture line of the gastric remnant, which was classified as type 0-IIc according to the Paris classification. ME-NBI at the oral side of the lesion revealed the absence of the microsurface pattern (MSP) and scattered microvessels with dilation and caliber variation, while ME-NBI at the anal side showed an irregularly tubular MSP. An endoscopic forceps biopsy showed a well- to moderately differentiated adenocarcinoma. Interventions: We performed endoscopic submucosal dissection, and en bloc resection of the tumor was successfully achieved. Outcomes: The histological findings showed two distinct components: neuroendocrine carcinoma (NEC) and well-differentiated adenocarcinoma, which comprised ∼60% and 40% of the tumor, respectively. The NEC component corresponded to the site with the absence of an MSP and scattered microvessels on ME-NBI, while the well-differentiated adenocarcinoma component corresponded to the site with an irregularly tubular MSP. The pathological diagnosis was mixed adenoneuroendocrine carcinoma, infiltrating into the deep submucosal layer. Lessons: We propose that the absence of an MSP plus an irregular MSP is characteristics of gMANEC, which was useful for the diagnosis of gMANEC before treatment.

We aimed to determine the pathogenesis of gastric mixed adenoneuroendocrine carcinoma (MANEC) and pure neuroendocrine carcinoma (NEC), which is largely unknown. Targeted DNA sequencing was performed on 34 tumor samples from 21 patients - 13 adenocarcinoma (ADC)/NEC components from MANECs and eight pure NECs - and 21 matched non-neoplastic gastric tissues. Mutational profiles of MANECs/NECs were compared with those of other tumors using public databases. The majority (64.1%; 59/92) of mutations in MANEC were shared by both ADC and NEC components. TP53 was the most commonly mutated gene in MANEC (69.2%, 9/13) and pure NEC (87.5%, 8/9). All TP53 mutations in MANEC were pathogenic mutations and were shared by both ADC and NEC components. A subset of TP53WT MANECs had a microsatellite-unstable phenotype or amplifications in various oncogenes including ERBB2 and NMYC, and the only TP53WT pure NEC harbored MYC amplification. Compared to NEC in other organs, NECs arising from the stomach had unique features including less frequent RB1 mutations. Differentially altered genes of MANEC ADC components were significantly associated with receptor tyrosine kinase signaling pathways, while differentially altered genes of MANEC NEC components were significantly associated with the NOTCH signaling pathway. Our data provide evidence suggesting a possible clonal origin of ADC and NEC components of MANEC, and we found that gastric MANECs and pure NECs are distinct entities with unique mutational profiles and underlying protein networks. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Gastroenteropancreatic neuroendocrine carcinomas (GEP-NENs) represent a heterogeneous group of rare tumors. The incidence of GEP-NENs has increased worldwide over the past decades, with the small intestine, rectum, and pancreas as the most common tumor locations. The epidemiological characteristics, pathogenesis and treatment have raised many questions, and some of them are still being debated. Here, we report a case of gastric collision tumor with large-cell neuroendocrine carcinoma and adenocarcinoma. A 73-year-old male patient with a history of gastric resection performed 30 years ago, with no medical records revealing the type of resection or the reconstructive way, presented with epigastric pain. The endoscopy revealed a solid, ulcerated mass at the gastrojejunal anastomosis site from which a tissue biopsy was taken, which was reported as adenocarcinoma. For staging, the patient underwent an abdominal CT scan, which showed the thickening of the gastric wall adjacent to anastomosis and perilesional adenopathy. The patient underwent a subtotal gastrectomy and regional lymphadenectomy. A diagnosis of large-cell neuroendocrine carcinoma developed on the gastric stump associated with isolated foci of moderately differentiated tubular adenocarcinoma pT3N1G3 was made. Immunohistochemical analysis is essential for the diagnosis and classification of the lesion. To confirm the diagnosis, Chromogranin A and Synaptophysin are needed, and for prognostic evaluation the identification of Ki-67 and mitotic figure count are required.

Gastric mixed adenoneuroendocrine carcinoma (MANEC) is a clinically aggressive subtype of mixed neuroendocrine–nonneuroendocrine neoplasm (MiNEN) with unclear clonal origin. In this study, we analyzed high-resolution copy number (CN) profiling data using the OncoScan CNV Assay in the neuroendocrine carcinoma (NEC) and adenocarcinoma components of eight MANECs. Some common CNVs, including the gain of CCNE1 (19q12) and the loss of FAT1 (4q35.2), were frequently detected in both components; these CNVs were verified by FISH, qPCR and immunohistochemistry staining assays in samples with sufficient material. The identification of common CNVs in both components supports the likelihood of single clonal origin of morphologically heterogeneous tumor cells and suggests several novel genetic events potentially involved in the development of gastric MANEC. We also detected and validated some CNVs and alterations specific for the NEC component, such as MAPK1 loss and MAPK signaling pathway alterations, which could contribute to the neuroendocrine differentiation of gastric MANEC. In addition, we found that the NEC component presented more CNVs and greater CN loss than the adenocarcinoma component (P = 0.007 and P = 0.004, respectively); the NEC components from different cases were not clustered in the hierarchical clustering analysis, indicating the marked genetic heterogenicity of the NEC component in gastric MANEC. In summary, this study describes the cytogenetic characteristics of each component of gastric MANEC, providing some clues for further studies on the development and progression of gastric MANEC as well as providing some potential therapeutic targets.

Gastric mixed adenoneuroendocrine carcinomas (G-MANEC) are rare malignancies with about 40 cases reported to date in English literature. Clinically, G-MANEC is characterized by aggressive behavior with rapid progression including a high incidence of regional and distant metastasis, leading to tumor-related death without any chance of surgical resection. Moreover, there is no uniform standard adjuvant chemotherapy for G-MANEC. Here, we report a case of G-MANEC with extensive liver metastases that gained survival benefits from neoadjuvant chemotherapy. A brief discussion of the biological behavior and treatment of G-MANEC is presented.

Cancers exhibiting a combination of epithelial and neuroendocrine features can occur in various organs. In the WHO classification of neoplasms of the gastrointestinal tract, such tumors are called “mixed adenoneuroendocrine carcinomas”. They may be composite, combined or amphicrine type. We present here a rare case of composite adenocarcinoma and neuroendocrine carcinoma of stomach. Keywords: MANEC, Composite tumour, Stomach.

Mixed adenoneuroendocrine carcinomas are rare tumors that contain both an exocrine and an endocrine component. Since the latest classification by the World Health Organization and with the aid of immunostaining, more mixed adenoneuroendocrine carcinomas are now identified and diagnosed. Nonetheless, our knowledge of these tumors is still limited, notably concerning gastric variants, as the cases reported in the literature are very limited. The clinical and surgical treatment, including the chemotherapy schemes, the prognosis, and recurrence still represent challenges for the medical teams. We present the case of a 62-year-old woman. After an upper endoscopy revealed multiple polyps and a low-grade neuroendocrine tumor, a D2 radical gastrectomy was performed. A low output esophageal anastomotic leak was discovered in the postoperative period and successfully managed. Pathology revealed a gastric mixed adenoneuroendocrine carcinoma, the first case of this kind reported in Ecuador. Patient is doing well and under constant surveillance up until her 13th postoperative month.

The endoscopic and pathological features of early gastric mixed adenoneuroendocrine carcinoma (MANEC), as well as its carcinogenesis, remain largely unclear. Screening esophagogastroduodenoscopy was performed on an 80-year-old man, revealing 3 superficial elevated lesions. Endoscopic submucosal dissection (ESD) was performed, and the patient was diagnosed with intramucosal gastric cancer comprising mixed adenocarcinoma and neuroendocrine tumor, well-differentiated adenocarcinoma and well-differentiated adenocarcinoma, with negative margins. To our knowledge, this is the first report describing the endoscopic and pathological findings of synchronous triple gastric cancer incorporating mixed adenocarcinoma and neuroendocrine tumor completely resected with ESD.

Background To assess the prognostic factors and investigate the optimal treatment of gastric mixed adenoneuroendocrine tumors. Methods We retrospectively analyzed clinical data from 80 patients with gastric mixed adenoneuroendocrine carcinoma that received radical resection in our department from January 2007 to December 2016. Risk factors for relapse and survival were analyzed using a multivariate Cox proportional hazards regression model. Gastric mixed adenoneuroendocrine carcinoma was divided into neuroendocrine carcinoma and adenocarcinoma based on the predominant type in the tumor. Results The 3-year overall survival was 40% in the neuroendocrine carcinoma group and 75% in the adenocarcinoma group (P = 0.006). The neuroendocrine carcinoma (NEC)-dominant tumors and a Ki-67-positive index ≥60% were independent risk factors for worse overall survival. The 3-year recurrence-free survival was 33% in the neuroendocrine carcinoma group and 68% in the adenocarcinoma group. NEC-dominant tumors and a Ki-67-positive index ≥60% were independent risk factors for gastric mixed adenoneuroendocrine carcinoma recurrence. Patients in the adenocarcinoma group that received adjuvant chemotherapy exhibited significantly better overall survival than patients that did not receive chemotherapy (median survival time 43 months vs. 13 months, P = 0.026). Conclusion The NEC-dominant tumors and a Ki-67-positive index ≥60% were significantly associated with worse survival and a higher recurrence rate for gastric mixed adenoneuroendocrine carcinoma patients. Patients in the adenocarcinoma group may benefit from gastric adenocarcinoma treatments. Electronic supplementary material The online version of this article (10.1186/s12885-018-4943-z) contains supplementary material, which is available to authorized users.

Gastric mixed adenoneuroendocrine carcinoma, a rare malignant type of stomach tumor, is composed of components of adenocarcinoma and neuroendocrine tumor. This type of neoplasm usually has a poor prognosis since both components are malignant. A 65-year-old male presented with norexia, epigastric distention, abdominal and lumbar pain. Contrast computed tomography scan of the abdomen verified multiple lesions merged into a large mass. Histolopathological examination of the specimen from digestive endoscopy was verified to be gastric mixed adenoneuroendocrine carcinoma. The patient received a multimodality treatment of chemotherapy, surgical resection with radiotherapy and still remains alive with no evidence of metastasis or recurrence for over 5 years. The authors suggest that multimodality therapy may be beneficial and necessary to effictively treat mixed adenoneuroendocrine carcinoma.

The occurrence of gastric mixed adenoneuroendocrine carcinoma (MANEC) is relatively rare, although a few cells of gastric adenocarcinoma frequently show neuroendocrine differentiation [1]. We herein present one of only a few reported cases of gastric MANEC with trilineage histologic differentiation, composed of adenocarcinoma, large cell neuroendocrine carcinoma (NEC), and squamous cell carcinoma (SqCC).

Rationale: This article is aimed to retrospect the clinicopathological data of 2 cases of gastric MANENCs. MANEC is a rare biphasic tumor type that is coexistence of dual neuroendocrine and adenocarcinoma differentiation with each composing exceeding 30% volume. Gastric MANEC have just been reported anecdotally in the literature due to their rarity and heterogeneity. According to our study, these neoplasms have 3 different metastasis patterns: only adenocarcinomatous or neuroendocrine carcinoma and both of the 2 components. We first focus on the correlation of metastasis characteristics with prognosis in gastric MANEC, which may be potential implications for the choice of chemotherapy. Patient concerns: The 2 cases of patient shared several symptoms: epigastric discomfort, weight loss, hematemesis, or melena. Diagnosis: The 2 patients were diagnosis as MANEC based on the identification of histopathological analysis. In case 1, the poor differentiated adenocarcinoma accounted for 30%, the neuroendocrine part account for 70% and both of the 2 components metastasized to the lymph nodes, whereas in case 2, poorly differentiated adenocarcinoma accounted for 70%, the neuroendocrine part for 30% and only the glandular component invaded regional lymph nodes. Interventions: The first patient underwent laparoscopic radical gastrectomy and underwent adjuvant chemotherapy, combination of cisplatin, and etoposide successfully. The second patient received radical gastronomy, and did not receive any chemotherapy due to general weakness. Outcomes: The first patient is alive with no evidence of recurrence, and the second patient died 6 months after the operation. Lessons: The assessment of metastatic sites should be a routine pathological practice, which is crucial for clinical decision-making and the selection of management.

A 75-year-old man was diagnosed with gastric cancer. Fifty years previously, he had undergone gastroenterostomy with a Braun enteroenterostomy. At present, a distal gastrectomy and small intestinal partial resection were performed. Intraoperatively, the tumor was localized to the previous stomal site. HE staining showed that the tumor comprised two elements: a tubular adenocarcinoma on the gastric side and a neuroendocrine carcinoma (NEC) on the jejunal side. The final pathologic diagnosis was mixed adenoneuroendocrine carcinoma based on an immunohistochemical analysis of endocrine markers and an elevated Ki-67 labeling index. The risk of later cancer development cancer recurrence near the gastrojejunostomy site is well known. Potentially, chronic enterogastric bile reflux may irritate the gastric mucosa and act as a promoter. Gastric NEC has a strong malignant potential. We suspect that, in the present case, the constant exposure to secondary bile may have induced a gastric mucosal adenocarcinoma, which finally differentiated into a NEC.

Rationale: Mixed adenoneuroendocrine carcinoma (MANEC) is a rare neoplasm, and consensus on the treatment is unavailable. Patient concern: A 60-year-old Chinese man presented with obstructive symptoms while eating and paroxysmal stomach pain for more than a month. Diagnosis: MANEC was diagnosed based on clinical manifestations, imaging findings, and pathological examinations. Interventions: The patient underwent radical gastrectomy and received XELOX adjuvant chemotherapy (oxaliplatin 200 mg day 1 + capecitabine 1.5 g twice a day) after surgery. Outcomes: After 4 cycles of XELOX adjuvant chemotherapy were administered, abdominal computerized tomography and liver magnetic resonance showed liver metastasis. Lessons: The therapy of gastric MANEC is based on surgical operation, and adjuvant chemotherapy program has an important influence on its prognosis. Therefore, further studying the effectiveness of XELOX adjuvant chemotherapy for gastric MANEC is necessary.

A flat, elevated lesion measuring 5 mm in diameter was found in the gastric body of an 80-year-old man. A biopsy showed moderately differentiated adenocarcinoma, and endoscopic ultrasonography revealed a hypoechoic mass located in the submucosa. Endoscopic submucosal dissection was subsequently performed, and a pathological examination revealed a tumor composed of adenocarcinoma and neuroendocrine carcinoma with submucosal infiltration. The pathological diagnosis was gastric mixed adenoneuroendocrine carcinoma (MANEC). An additional gastrectomy procedure was performed, and no recurrence was noted for at least three years. This case is interesting with respect to the carcinogenesis of endocrine cell carcinoma and MANEC.

Gastric mixed adenoneuroendocrine carcinomas (MANECs) are rare, with both the exocrine and neuroendocrine components exceeding 30% volume. Several classifications for MANECs have been proposed, yet they have not been clinically evaluated. The aim of this study was to evaluate the correlation between tumor grade, histologic characteristics, and prognosis of gastric MANECs. We collected eligible 14 cases in our series and 31 cases in the literature and compared the prognostic difference among gastric MANECs with different histologic characteristics. Gastric MANECs could be divided into subgroups according to tumor grade of the neuroendocrine component and adenocarcinoma types. The high grade and large proportion of neuroendocrine component correlated with aggressive behavior and a tendency of poor clinical outcome. Gastric MANECs with a poorly differentiated adenocarcinoma showed a significant lower survival rate than did MANECs with a differentiated adenocarcinoma or mucin-producing carcinoma (P = .0008). Gastric MANECs were a heterogeneous group with different tumor grades, histologic subtypes, combination patterns, and patient outcomes. Previous classifications were evaluated. This study proves that histologic characteristics correlate with clinical outcomes. Our findings are complements to the latest prognostic classification.

Most gastric neuroendocrine tumours are well differentiated and considered as neuroendocrine neoplasms, whilst poorly differentiated lesions are considered as neuroendocrine carcinomas and account for only 6–16% of gastric neuroendocrine tumours. Gastric mixed adenoneuroendocrine carcinomas are rare malignancies usually composed of a neuroendocrine carcinoma and an adenocarcinoma with a variable grade of differentiation. Here, we report an unusual and rare gastric mixed adenoneuroendocrine carcinoma with a trilineage cell differentiation including a neuroendocrine carcinoma, an adenocarcinoma and a squamous cell carcinoma. A brief discussion of the histopathological features, biological behaviour and treatment of this rare tumour type is presented.

[Excerpt] Gastrointestinal mixed adenoneuroendocrine carcinomas (MANECs) are rare tumors and, as the name implies, are characterized by the presence of both components, exocrine and neuroendocrine, each one representing at least 30% of the lesion.1 It is unclear if they originate from proliferation of different cell lineages or from stem cells capable of differentiating along multiple cell lineages. They may present as polypoid lesions, with variable size. Treatment and prognosis is determined by the more aggressive component. […], (undefined)

Composite tumors in the stomach composed of adenocarcinoma and neuroendocrine carcinoma are rare. We herein report a case of intramucosal gastric mixed adenoneuroendocrine carcinoma (MANEC) that was treated with endoscopic submucosal dissection (ESD). A 77-year-old man who had previously received ESD for early gastric adenocarcinoma underwent esophagogastroduodenoscopy for screening, which showed a depressed lesion on the lesser curvature of the antrum. The tumor was removed en bloc via ESD and pathologically diagnosed as MANEC. The tumor was located within the mucosal layer, and no lymphovascular invasion was evident. Seven months after the ESD procedure, the patient is currently feeling well without recurrence or metastasis.

Small cell carcinoma of the stomach, which is considered synonymous with neuroendocrine carcinoma, is rare. We encountered a case of mixed adenoneuroendocrine carcinoma. Gastrointestinal endoscopy revealed a type 0 IIa + IIc lesion in the stomach. Biopsy suggested well-differentiated adenocarcinoma. Endoscopic submucosal dissection was performed and gastric cancer comprising both well to moderately differentiated adenocarcinoma within the mucous membrane and small cell carcinoma invading to the submucosa with accompanying vessel invasion was found. Mixed adenoneuroendocrine carcinoma was diagnosed and the small cell carcinoma was thyroid transcription factor-1 positive. No tumor lesions were apparent in other organs, so distal gastrectomy and lymph node dissection were performed. Lymph node metastases were not observed. The patient is currently alive without recurrence. Thyroid transcription factor-1-positive gastric neuroendocrine carcinoma is very rare, and the thyroid transcription factor-1-positive rate may contribute to the prediction of prognosis and treatment selection. Accumulation of cases is thus very important.

A 47-year-old African-American man presented to the emergency department with upper abdominal pain, nausea and vomiting. His symptoms were aggravated by eating. He reported 32 kg unintentional weight loss over 2 months’ period. Abdominal examination revealed tenderness in the epigastric region. Abdominal CT scan showed mural wall thickening involving the gastric antrum and pylorus (figure 1). Subsequent oesophagogastroduodenoscopy (EGD) revealed a large mass occupying the gastric antrum (figure 2). Initial biopsy from the gastric mass showed poorly differentiated adenocarcinoma. Figure 1 (A) Coronal section of the CT abdomen with intravenous and oral contrast showing wall thickening at the level of the gastric antrum. (B) Axial section of the CT abdomen with intravenous and oral contrast showing wall thickening at the level of the gastric antrum and pylorus. Figure 2 Upper gastrointestinal endoscopy showing a mass in the gastric antrum (A. B. C: different views). The patient underwent partial gastrectomy with gastrojejunostomy and the gastric specimen was examined. There was a transmurally invasive adenocarcinoma that has a remarkable variety of cell types and growth patterns, including tubular, mucinous, …