Mixed Neuroendocrine-non-neuroendocrine Neoplasms Research Articles

A case report of MiNEN: concomitant primary small-cell neuroendocrine carcinoma and high-grade papillary urothelial carcinoma of the urinary badder. Composite or Collision Tumor?

Bladder cancer is the tenth most diagnosed cancer worldwide, and urothelial carcinoma is the most common histologic type. On the contrary, small primary cell neuroendocrine carcinoma of the bladder is sporadic and accounts for less than 1% of all bladder tumors. These malignancies can be observed in mixed neuroendocrine/non-neuroendocrine neoplasms (MiNENs), which have been studied more in the gastrointestinal tract and lungs but scarcely in this organ due to their low incidence. There are concerns about the pathogenic connection between these two tumors, and the limited evidence accounts for the lack of consensus regarding prognosis and treatment for these patients; therefore, they may need a multimodal approach. Here, we describe the case of a 63-year-old woman who presented with gross hematuria, weight loss, and hypogastric discomfort for the past five months. An intravesical mass was found, and transurethral resection was performed. The Histopathology revealed a high-grade papillary urothelial carcinoma with an invasive component through muscularis propria of the bladder, so she was taken to radical cystectomy with extended pelvic lymphadenectomy. The final pathology report revealed an accompanying primary small cell neuroendocrine carcinoma intermingled with the urothelial one. She received postoperative adjuvant chemotherapy and finally died six months after surgery.

Efficacy and Toxicity Analysis of mFOLFIRINOX in High-Grade Gastroenteropancreatic Neuroendocrine Neoplasms.

High-grade neuroendocrine neoplasms (NENs) comprise both well-differentiated grade 3 neuroendocrine tumors (G3 NETs) and poorly differentiated neuroendocrine carcinomas (NECs). Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) nearly always include poorly differentiated NEC as the neuroendocrine component. The efficacy and safety of frontline mFOLFIRINOX chemotherapy has never been investigated in patients with high-grade NENs. We conducted a multi-institutional retrospective analysis of patients with advanced high-grade NEN of the gastroenteropancreatic tract or of unknown origin seen between February 2016 and April 2023 who received treatment with frontline mFOLFIRINOX. A total of 35 patients were included (G3 NETs: n=2; NECs: n=25; MiNENs: n=8; stage III: n=5; stage IV: n=30). The objective response rate was 77% (complete response: 3%; partial response: 74%). Median progression-free survival was 12 months (95% CI, 9.2-16.2 months) and median overall survival was 20.6 months (95% CI, 17.2-30.6 months). No significant differences in efficacy were seen according to primary site, histopathology, and Ki-67 proliferative index. All 5 patients with stage III disease who received mFOLFIRINOX obtained an objective response and underwent radical surgery or definitive radiotherapy with curative intent, with a recurrence rate of 40%. Grade 3 or 4 adverse events were observed in 43% of patients (mainly neutropenia and diarrhea). Females were at significantly increased risk of developing severe toxicities. mFOLFIRINOX shows antitumor activity against high-grade NENs. Well-designed, prospective clinical trials are needed to assess the efficacy of mFOLFIRINOX in both the neoadjuvant and metastatic settings.

Efficacy analysis of 7 cases of mixed neuroendocrine-nonneuroendocrine neoplasm of the duodenal papilla

The clinical data of 7 patients diagnosed with mixed neuroendocrine-nonneuroendocrine neoplasm were analyzed in the Department of Hepatobiliary Surgery of Hunan Provincial People's Hospital from January 2016 to December 2022. Among the 7 patients, 5 were male and 2 were female, with an average age of 59.3 years. Its clinical characteristics are similar to malignant ampulla tumors, and it is difficult to differentiate them. The preoperative puncture biopsy positivity rate is low, making it difficult to diagnose preoperatively, and the prognosis is worse.Comprehensive treatment including surgery, chemotherapy, and radiotherapy can be the preferred treatment option for this disease.

Mixed neuroendocrine non-neuroendocrine neoplasms in gastroenteropancreatic tract.

Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) are a heterogeneous group of malignant neoplasms that can settle in the gastroenteropancreatic tract. They are composed of a neuroendocrine (NE) and a non-NE component in at least 30% of each tumour. The non-NE component can include different histological combinations of glandular, squamous, mucinous and sarcomatoid phenotypes, and one or both of the components can be low-or high grade malignant. Recent changes in the nomenclature of these neoplasms might lead to great deal of confusion, and the lack of specific clinical trials is the main reason why their management is difficult. The review aims to clarify the definition of MiNEN and analyze available evidence about their diagnosis and treatment options according to their location and extension through careful analysis of the available data. It would be important to reach a general consensus on their diagnosis in order to construct a classification that remains stable over time and facilitates the design of clinical trials that, due to their low incidence, will require long recruitment periods.

Gastric Carcinoma in Autoimmune Gastritis: A Histopathologic and Molecular Study

Patients with autoimmune gastritis (AIG) have a 13-fold risk of developing type-1 neuroendocrine tumors, whereas the risk for gastric adenocarcinoma is still uncertain. Here we describe the clinicopathologic and molecular features of a series of gastric carcinomas (GC) arising in the context of AIG. A total of 26 AIG-associated GC specimens were collected from 4 Italian Institutions. Immunohistochemistry for MUC1, MUC2, MUC5AC, MUC6, CDX2, HER2, PD-L1, CLDN18, mismatch repair (MMR) proteins, and p53 and EBV-encoded RNA (EBER) in situ hybridization were performed. Histologic and immunohistochemical features were jointly reviewed by 5 expert gastrointestinal pathologists. Next-generation sequencing analysis (TrueSight Oncology 500, Illumina) of 523 cancer-related genes was performed on 19 cases. Most tumors were diagnosed as pT1 (52%) and they were located in the corpus/fundus (58%) and associated with operative link for gastritis assessment stage II gastritis (80.8%), absence of parietal cells, complete intestinal metaplasia, and enterochromaffin-like-cell micronodular hyperplasia. Only 4 (15.4%) GCs were diagnosed during follow-up for AIG. The following histotypes were identified: 20 (77%) adenocarcinomas; 3 (11%) mixed neuroendocrine–non-neuroendocrine neoplasms, and 2 (8%) high-grade solid adenocarcinomas with focal neuroendocrine component, 1 (4%) adenocarcinoma with an amphicrine component. Overall, 7 cases (27%) showed MMR deficiency, 3 (12%) were positive (score 3+) for HER2, 6 (23%) were CLDN18 positive, and 11 (42%) had PD-L1 combined positive score ≥ 10. EBER was negative in all cases. Molecular analysis revealed 5/19 (26%) microsatellite instability (MSI) cases and 7 (37%) tumor mutational burden (TMB) high. The most frequently altered genes were TP53 (8/19, 42%), RNF43 (7/19, 37%), ERBB2 (7/19, 37% [2 amplified and 5 mutated cases]), ARID1A (6/19, 32%), and PIK3CA (4/19, 21%). In summary, AIG-associated GCs are often diagnosed at low stage in patients with longstanding misrecognized severe AIG; they often display a neuroendocrine component or differentiation, have relatively higher rates of MMR deficiency, and TMB high.

Colorectal neuroendocrine carcinoma and mixed neuroendocrine-non-neuroendocrine neoplasm: Prognostic factors and PD-L1 expression

Colorectal neuroendocrine carcinoma (NEC) and mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) are rare malignancies with unclear boundaries and poor prognoses. Our study aimed to conduct a comparative analysis of these diseases, identify prognostic factors, and explore potential therapeutic targets. We collected and analyzed clinicopathological data of NEC and MiNEN in our hospital from 2011 to 2020. Immunohistochemical staining for PD-L1, BRAF V600E, and mismatch repair proteins was performed. We identified 14 NEC and 7 MiNEN cases. Demographic data, including median overall survival (17.1 months for NEC and 18.5 months for MiNEN), did not significantly differ. NEC showed a higher tendency to occur in the rectum and sigmoid colon (p = 0.025) and had fewer cases with metastatic adenocarcinoma components in lymph nodes (p = 0.009) compared to MiNEN. Adverse prognostic factors were age ≥70 years (p = 0.012), N2 nodal status (p = 0.032), and stage IV disease (p = 0.013) based on multivariate Cox regression analysis. We identified five PD-L1 positive cases, two BRAF V600E mutated cases, and one Lynch syndrome case with MSH2 and MSH6 loss. Patients with colorectal NEC or MiNEN exhibited poor survival rates. Adverse prognostic factors included older age, N2 nodal status, and distant metastasis. Potential therapeutic avenues such as immune checkpoint and BRAF inhibitors were suggested for patients with these carcinomas.

An Italian real-world multicenter study of patients with advanced mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) of the gastro-entero-pancreatic system treated with chemotherapy.

The aim of this study is to describe the clinical management of an Italian series of patients with advanced gastro-entero-pancreatic (GEP) MiNENs treated in clinical practice. Clinical records of patients from four Italian referral Centers were retrospectively analyzed to correlate clinical/biological data with clinical outcomes. All the surgical specimens were centrally reviewed. Clinical data and surgical samples of 51 patients during 1995-2015 were analyzed. Sites of origin were: 32 colorectal, 14 gastro-esophageal, and 5 pancreatobiliary. Twenty-one out of fifty-one (42.2%) developed metachronous distant metastases. Only 5/51 (9.8%) patients received peri-operative therapy, and 23/51 (45.1%) first-line chemotherapy, mostly fluoropyrimidines/oxaliplatin. The NEN component was poorly differentiated in the whole population. Patients with Ki67 index < 55% in the NEC component had a significantly longer median overall survival (OS) (35.3months; 95% CI 27.1-41.0) than those with Ki67 ≥ 55% (11.9months; 95% CI 9.1-14.0) P = 0.0005. The median OS was 14months (95% CI 10.1-19.1) in the whole cohort, with 11.4months (95% CI 6.2-20.2) in patients who received a first-line therapy. This study confirms that GEP-MiNENs represent a complex disease and that over the past years the clinical management has been predominantly guided by the subjective judgment of the clinicians. Although, in this series, the NEC component appeared mostly responsible for the systemic spread and prognosis on the whole neoplasm, the lack of strong prognostic and predictive factors universally recognized seems to condition their management so far. Future prospective clinical and biomolecular studies could help clinicians to improve clinical management of GEP-MiNENs.

Primary Oral Mixed Neuroendocrine-Non-neuroendocrine Neoplasm (MiNEN): A Rare Case Report and Review of the Literature.

Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) are rare tumors recently characterized by the presence of both neuroendocrine and non-neuroendocrine components within the same tumor tissue. Although MiNEN found their place in the WHO classification for various organs, this composite tumor in the head and neck region remains exceptionally rare. We present a case of primary oral MiNEN in a 64-year-old male located on the left side of lower gingiva. Biopsy raised suspicion of neuroendocrine carcinoma (NEC) and the patient underwent partial mandibulectomy. The resected specimen showed two distinct components of NEC and squamous cell carcinoma (SCC) with the confirmation of immunohistochemical markers. There has been no sign of recurrence nor metastasis 6years after the surgery. In addition, we have conducted a review of published cases with potential relevance to this entity, resulting in five cases. The diverse terminology reinforces the need for a standardized classification system of oral/head and neck MiNENs.

Rectal MiNEN: A rare case report

Rectal mixed neuroendocrine non-neuroendocrine neoplasms (MiNEN) are rare tumors with two components, neuroendocrine and non-neuroendocrine, each comprising 30% of all tumors. There have been limited studies on the epidemiology, clinical and prognostic characteristics of these tumors. Here, we report a case series of two cases of rectal MiNEN from a tertiary care center in North East India. These tumors are known to be aggressive and often with poor prognosis.

Clinical characteristics of mixed neuroendocrine non-neuroendocrine neoplasm (MiNEN): a single institution case series

Clinical characteristics of mixed neuroendocrine non-neuroendocrine neoplasm (MiNEN): a single institution case series

A Case of Gastric Mixed Neuroendocrine-Nonneuroendocrine Neoplasm Composed With Adenoma and Neuroendocrine Tumor

Mixed neuroendocrine-nonneuroendocrine neoplasms (MiNENs) of the gastrointestinal tract, particularly gastric MiNENs are rare, and a gastric adenoma that occurs concomitant with a neuroendocrine carcinoma (and not gastric adenocarcinoma) is extremely rare. The clinicopathologic and pathogenetic features of MiNENs remain unclear, and treatment guidelines are currently unavailable. A 75-year-old man patient was referred to our hospital for management of a gastric adenoma. Endoscopy revealed an elevated mucosal lesion (10 mm×10 mm) at the greater curvature of the lower gastric body. The patient underwent endoscopic submucosal dissection for removal of the gastric neoplasm. Histopathological evaluation revealed mixed epithelial dysplasia, low and partly high grade and a neuroendocrine tumor (grade 1). Immunohistochemical analysis showed neoplastic cells with immunopositivity for CD56, synaptophysin, and INSM1, and Ki-67 showed 2.2%. Therefore, the patient was diagnosed with a low-grade gastric MiNEN. We present a rare case of gastric MiNENs (adenoma-neuroendocrine tumor) together with a literature review.

Claudin 18.2 expression in digestive neuroendocrine neoplasms: a clinicopathological study.

Claudin 18.2-targeted therapy has shown significant efficacy in treating claudin 18.2-positive cancers. However, limited systematic studies have investigated characteristics of claudin 18.2 expression in neuroendocrine neoplasms (NENs). Data and specimens from 403 cases of digestive NENs were retrospectively collected, and claudin 18.2 expression was detected using immunochemical staining. Claudin 18.2 was positive in 19.6% (79/403) of the digestive NENs. The highest positive rate of claudin 18.2 was observed in gastric NENs (72/259, 27.8%), accounting for 91.1% (72/79) of all positive cases. The positivity rate was significantly higher in gastric NENs compared to pancreatic (2/78, 2.6%) or colorectal NENs (2/38, 5.3%; p < 0.05). For digestive NENs, claudin 18.2 positivity was significantly higher in neuroendocrine carcinomas (NECs) (37/144, 25.7%) than in neuroendocrine tumours (NETs; 14/160, 8.8%; p < 0.001), but no significant difference was found between gastric NECs (59/213, 27.7%) and gastric NETs (13/46, 28.3%; p > 0.05). The positivity was significantly higher in large-cell NECs (LCNECs; 28/79, 35.4%) and MiNEN (mixed neuroendocrine-non- neuroendocrine neoplasms)-LCNECs (23/66, 34.8%) compared to small-cell NECs (SCNECs; 9/65, 13.8%) and MiNEN-SCNECs (5/33, 15.2%; p < 0.05). Claudin 18.2 expression was more prevalent in gastric NENs than in pancreatic (12.5 ×; p = 0.001) and colorectal NENs (5.9 ×; p = 0.021). Claudin 18.2 staining was a useful method for identify the gastric origins of NETs, with a sensitivity of 28.3% and a specificity of 99.1%. The expression characteristics of claudin 18.2 in NENs were characterized, which may provide a clinicopathological reference for targeted therapies in patients with NENs.

Epidemiology and survival outcomes of colorectal mixed neuroendocrine–non-neuroendocrine neoplasms and neuroendocrine carcinoma

BackgroundMixed neuroendocrine–non-neuroendocrine neoplasms are a rare subtype of neuroendocrine neoplasm consisting of ≥30% each of neuroendocrine and non-neuroendocrine differentiation. Neuroendocrine carcinomas are poorly differentiated neuroendocrine tumors. The epidemiology and prognosis of colorectal mixed neuroendocrine–non-neuroendocrine neoplasms and neuroendocrine carcinomas are not clearly defined in the literature. We sought to examine the presentation, patterns of care, and outcomes of patients with mixed neuroendocrine–non-neuroendocrine neoplasms and neuroendocrine carcinomas. MethodsWe identified patients diagnosed with stage I–III colorectal (excluding appendix) mixed neuroendocrine–non-neuroendocrine neoplasms or neuroendocrine carcinomas with only one-lifetime cancer diagnosis who underwent surgical resection between 2010 and 2018 from the National Cancer Database. We performed bidirectional selection to identify variables to include in a multivariable Cox proportional hazards model. ResultsWe identified 189 patients with a diagnosis of stage I to III colorectal mixed neuroendocrine–non-neuroendocrine neoplasms, 66% of whom had poorly differentiated tumors and 482 with neuroendocrine carcinomas. Among patients with stage III disease, 68% of patients with mixed neuroendocrine–non-neuroendocrine neoplasms and 54% of patients with neuroendocrine carcinomas received adjuvant chemotherapy. The median survival for the overall patients with mixed neuroendocrine–non-neuroendocrine neoplasms and neuroendocrine carcinomas cohorts were 38 and 42 months, respectively (P = .22), and the median survival for patients with mixed neuroendocrine–non-neuroendocrine neoplasms and neuroendocrine carcinomas with stage III disease were 30 and 25 months, respectively (P = .27). In multivariable analysis, fewer number of positive nodes and receipt of adjuvant chemotherapy were independently associated with decreased risk of mortality for patients with mixed neuroendocrine–non-neuroendocrine neoplasms and neuroendocrine carcinomas. ConclusionAdjuvant chemotherapy is associated with improved survival in stage III mixed neuroendocrine–non-neuroendocrine neoplasms and neuroendocrine carcinomas. Future studies are warranted to identify subsets of patients benefiting most from adjuvant therapy.

Gene expression profiling of pancreatic neuroendocrine carcinoma and mixed neuroendocrine-non-neuroendocrine neoplasm

Pancreatic neuroendocrine carcinoma (NEC) and mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) are rare pancreatic malignant tumors, and comprehensive gene analyses are scarce. In this study, six NECs and six MiNENs were collected, immunohistochemistry for synaptophysin, chromogranin A, INSM1, Ki-67, and Rb was conducted, and KRAS mutational status was examined. Among these cases, comprehensive gene expression analysis of oncogene pathways using nCounter® were performed with six NECs and four MiNENs, and those data were compared with that of three pancreatic ductal adenocarcinomas (PDACs), with that of three normal pancreatic ducts, and with each other. By dividing NEC and MiNEN cases into KRAS-mutated group and KRAS-wild group, the difference of clinicopathological data and gene expression profiling data were examined between the two groups. Compared to the data of normal pancreatic epithelium, all 13 cancer-related pathways were upregulated in PDAC, MiNEN, and NEC group with more upregulation in this order. Compared to the data of PDAC, genes of DNA Damage repair pathway was most upregulated both in NECs and MiNENs. Regarding the difference between KRAS-mutated and KRAS-wild groups, several genes were differentially expressed between the two, where MMP7 was the upregulated gene with highest p-value and NKD1 was the downregulated gene with highest p-value in KRAS-mutated group. From the extent of upregulation of 13 pathways, MiNEN was considered more progressed stage than PDAC, and NEC was considered more progressed than MiNEN. From the comparison of KRAS-mutated and KRAS-wild NECs and MiNENs, several differentially expressed genes were identified in this study.

Mixed neuroendocrine-non-neuroendocrine neoplasm (minen) of the duodenum: a rare clinical case

The study presents a rare case of mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) of the duodenum in a somatically aggravated patient. Endoscopic, ultrasound, and CT diagnostic studies, which were performed during hospitalization for examination, could not unequivocally detect the exact organ location of the tumor. Due to the prevalence of liver metastasis processes, surgical methods of treatment were not indicated. The final diagnosis of a rare type of malignant neoplasm was made only by the results of a postmortem examination.

Incidence, survival, and prognostic factors for patients with gastrointestinal mixed neuroendocrine non-neuroendocrine neoplasms: a SEER population-based study.

Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) are a group of rare tumors with limited research currently available. This study aimed to analyze the incidence, survival, and prognostic factors of gastrointestinal MiNENs. We included data from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2019. We compared the clinicopathologic characteristics and survival rates between MiNENs and neuroendocrine tumors (NETs), and calculated the incidence of MiNENs. We utilized univariate and multivariate Cox analysis to assess independent factors of prognosis and established a nomogram to predict 1-, 2-, and 3-year cancer-specific survival (CSS). Calibration and receiver operating characteristic (ROC) curves were drawn to validate the accuracy and reliability of the model. Decision curve analysis (DCA) was used to assess the clinical utility of the model. Patients with gastrointestinal MiNENs had a poorer prognosis than those with NETs. The overall incidence of gastrointestinal MiNENs has been increasing annually. Multivariate Cox regression analysis revealed that tumor size, lymph node metastasis, distant metastasis, and surgery were independent risk factors for CSS in MiNENs patients. Based on these risk factors, the 1-, 2-, and 3-year CSS nomogram model for MiNENs patients was established. Calibration, ROC, and DCA curves of the training and validation sets demonstrated that this model had good accuracy and clinical utility. Gastrointestinal MiNENs are rare tumors with an increasing incidence rate. The nomogram model is expected to be an effective tool for personalized prognosis prediction in MiNENs patients, which may benefit clinical decision-making.

Clinicopathological characteristics and oncological outcomes of three subtypes of neuroendocrine carcinoma of the cervix: A multicenter retrospective study of 288 patients in China.

87 Background: Neuroendocrine carcinoma of the cervix (NECC) is a rare pathological classification of cervical cancer, and is divided into small cell neuroendocrine carcinoma (SCNEC), large cell neuroendocrine carcinoma (LCNEC) and mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN). Present literature on NECC mainly focus on SCNEC, and the clinical features of LCNEC, especially MiNEN, are not well understood. Methods: A multicenter, retrospective study enrolled 288 patients. The primary outcomes were progression-free survival (PFS) and overall survival (OS). The Kaplan-Meier method and Cox proportional hazard analysis were performed to determine risk factors of PFS and OS. Results: With a median follow up of 25 months, the 5-year PFS of NECC, SCNEC, LCNEC and MiNEN was 40.2%, 40.4%, 30.3%, and 41.6%, respectively; and the 5-year OS was 45.4%, 44.0%, 32.3%, and 50.3%. In the whole cohort, it showed that LVSI (HR=1.996, 95%CI:1.275~3.126, p=0.003) and &gt;2/3 stromal invasion (HR=2.009, 95%CI:1.222~3.303, p=0.006) were independent risk factors of PFS; age&gt;45 (HR=1.956, 95%CI: 1.170~3.272, p=0.011), LVSI (HR=1.722, 95%CI: 1.016~2.918, p=0.043) and &gt;2/3 stromal invasion (HR=1.778, 95%CI: 1.024~3.087, p=0.041) were independent risk factors for OS. In patients undertaking surgery, it revealed that LVSI (HR=1.996, 95%CI:1.275~3.126, p=0.003) and NACT (HR=1.691, 95%CI: 1.040~2.748, p=0.034) were independent risk factors, and that adjuvant chemoradiotherapy was an independent protective factor of PFS (HR=0.201, 95%CI: 0.103~0.428, p&lt;0.001); age&gt;42 (HR=2.377, 95%CI: 1.417~3.986, p=0.001) and LVSI (HR=2.450, 95%CI: 1.388~4.324, p=0.002) were independent risk factors of OS, and that adjuvant chemoradiotherapy was an independent protective factor of OS (HR=0.175, 95%CI: 0.079~0.388, p&lt;0.001). Conclusions: This multicenter retrospective study first focused on three pathological subtypes of NECC including SCNEC, LCNEC and MiNEN. Patients with MiNEN did not have better prognosis, compared to patients with SCNEC and LCNEC at the same stage. LVSI and &gt;2/3 stromal invasion and adjuvant chemoradiotherapy are prognostic factors for PFS; age, LVSI, and &gt;2/3 stromal invasion and adjuvant chemoradiotherapy are prognostic factors for OS in patients with NECC. [Table: see text]

NET G3 vs NEC: p53 and Rb1 Immunolabeling in High-grade Gastrointestinal Neuroendocrine Neoplasms - Is It Enough for the Differential Diagnosis?

High-grade gastrointestinal neuroendocrine neoplasms (GI-NENs) are divided into well-differentiated G3 neuroendocrine tumors (NETs G3) and neuroendocrine carcinomas (NECs), having identical cut-offs of proliferation, but different biomolecular origins. This translates in distinct treatment choices. Our aim was to establish if p53/Rb1 immunohistochemical status in GI-NENs with Ki67 index >20% can predict the histopathological diagnosis. p53/Rb1 immunolabelling was performed on 42 cases of high-grade GI-NENs, diagnosed as NET G3, NEC and mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) with NEC component. Immunolabeled slides were digitally scanned, with automatic quantification of p53 and Rb1, blind to the diagnosis. The p53 positive percentage was stratified; two cut-offs were selected, naming the intervals as N (null, <1%), T (tumor, 1%-20%) and C (carcinoma, >20%). The Rb1 expression loss in >90% of neoplastic cells was considered mutational. NETs G3 mainly showed the T status (14/16, 87.5%), followed by N (1/16, 6.25%) and C (1/16, 6.25%); NECs and NEC components in MiNENs predominantly expressed the C status (19/26, 73.08%), followed by N (5/26, 19.23%) and T (2/26, 7.69%) (p<0.001, χ 2 =27.017). NET G3s showed positive expression for Rb1; 73.08% of NECs expressed negative Rb1 (p<0.001, χ 2 =21.351). NECs and NEC components in MiNENs showed Rb1 mutational status in 13 C cases (13/19, 68.42%), 4 N cases (4/5, 80%) and in both the T cases (p=0.002, χ 2 =11.187). Our results highlight the correlations between the p53/Rb1 immunostainings and the histopathological diagnosis of high-grade GI-NENs. NECs and NEC components in MiNENs showed a p53 mutational status (0% or 21-100%) and predominantly negative Rb1 expression. NETs G3 showed a p53 wild-type status (1-20%) and retained Rb1 expression. These findings suggest that the differential diagnosis of high-grade GI-NENs may benefit from p53/Rb1 immunohistochemical tests in everyday practice.

Mixed Neuroendocrine - Non-Neuroendocrine Neoplasm (MiNEN) - A Rare Heterogenous Malignancy of the Pancreas

Introduction: Pancreatic mixed neuroendocrine non-neuroendocrine neoplasms are extremely rare tumours accounting for 0.5% of all the pancreatic malignancies and 5% of all pancreatic neuroendocrine neoplasms. These tumors are rarely diagnosed preoperatively and they have a poor prognosis. Pancreatic MiNEN is characterized by 2 malignant lesions adenocarcinoma and Neuroendocrine tumour with each constituent involving more than 30% of the tumour. We report a case of 57yr old male with dullaching abdominal pain radiating to back. CA 19-9 was mildly elevated. Other laboratory tests are within normal limits. CECT abdomen revealed bulky pancreas with specks of calcification in the head of the pancreas and few tiny non enhancing hypodense areas and a well defined isodense lesion measuring 1.2x1.4cm in the second part of duodenum with enhancement in post contrast images associated with thickness of duodenal wall. The patient underwent Whipple’s pancreaticoduodenectomy with regional lymphadenectomy. Histopathological examination of specimen revealed an infiltrating acinar adenocarcinoma of the pancreas interspersed with a well differentiated neuroendocrine tumour component which made up of more than 45% of the tumour. The features were consistent with Mixed Neuroendocrine Non Neuroendocrine Neoplasm of the pancreas. Keywords: MiNEN, Pancreas, Neuroendocrine, Non neuroendocrine, Adenocarcinoma

Gastric amphicrine carcinoma: A histopathological diagnostic conundrum

Amphicrine carcinoma is rarely reported in literature. It is characterised by dual positivity of neuroendocrine markers and mucin stain in the same cells depicting divergent differentiation. Recently published WorldHealth Organisation (WHO) classification of neuroendocrine neoplasm of 2022 differentiates it from adenocarcinoma and mixed neuroendocrine-nonneuroendocrine neoplasms (MiNEN) it shows varied histomorphology and on rare occasions neuroendocrine features may not be evident in poorly differentiated carcinoma. Hence, diagnosis based solely on histomorphology can be misleading. This is a case of amphicrine carcinoma in an elderly female which showed poorly differentiated morphology along with signet ring cells. Same cells demonstrated immunopositivity for synaptophysin, chromogranin A and were also positive for mucin stains (PAS, PAS-D and Alcian blue). This case report, thus, emphasises the importance of neuroendocrine markers as a part of routine immunohistochemistry in poorly differentiated gastric carcinomas to aid diagnosis of amphicrine carcinoma.