Multimodal Management of Grade 1 and 2 Pancreatic Neuroendocrine Tumors

Pancreatic neuroendocrine tumors (p-NETs) are rare tumors with a recent growing incidence. In the 2017 WHO classification, p-NETs are classified into well-differentiated (i.e., p-NETs grade 1 to 3) and poorly differentiated neuroendocrine carcinomas (i.e., p-NECs). P-NETs G1 and G2 are often non-functioning tumors, of which the prognosis depends on the metastatic status. In the localized setting, p-NETs should be surgically managed, as no benefit for adjuvant chemotherapy has been demonstrated. Parenchymal sparing resection, including both duodenum and pancreas, are safe procedures in selected patients with reduced endocrine and exocrine long-term dysfunction. When the p-NET is benign or borderline malignant, this surgical option is associated with low rates of severe postoperative morbidity and in-hospital mortality. This narrative review offers comments, tips, and tricks from reviewing the available literature on these different options in order to clarify their indications. We also sum up the overall current data on p-NETs G1 and G2 management.

SOX11 is a sensitive and specific marker for pulmonary high-grade neuroendocrine tumors

Background Synaptophysin (SYN), chromogranin A (CGA), CD56 and insulinoma-associated protein 1 (INSM1) are proposed neuroendocrine (NE) markers used for diagnosis of pulmonary NE tumors. These NE markers have been identified in subsets of non-NE tumors requiring differential diagnosis, thus we sought to explore new NE markers. Methods We evaluated the immunohistochemical expression of SOX11, a transcription factor involved in neurogenesis, in pulmonary NE tumors and large cell carcinomas (LCCs). Results We found that SOX11 showed a sensitivity similar to INSM1 and CGA, and less than SYN and CD56 in small cell lung carcinomas (SCLCs) and large cell neuroendocrine carcinomas (LCNECs). While SOX11 is more specific than the other four markers for diagnosis of high-grade neuroendocrine carcinomas (HG-NECs) because 1) None of LCCs (0/63), the most challenging non-NE tumor type for differential diagnosis due to overlapped morphology with LCNECs displayed SOX11 positivity. While expression of at least one of SYN, CGA, CD56 or INSM1 was identified in approximately 60% (18/30) of LCCs. 2) SOX11 was only expressed in 1 of 37 carcinoid tumors in contrast to diffuse expression of SYN, CGA, CD56 and INSM1. In HG-NECs, we noticed that SOX11 was a good complementary marker for SCLC diagnosis as it was positive in 7 of 18 SYN−/CGA−/CD56− SCLCs and 3 of 8 SYN−/CGA−/CD56−/INSM1− SCLCs, and SOX11 positivity in 4 of 6 SYN−/CGA−/CD56− cases previously diagnosed as LCCs with NE morphology provides additional evidence of NE differentiation for reclassification into LCNECs, which was further confirmed by electromicroscopical identification of neurosecretory granules. We also found SOX11 expression cannot predict the prognosis in patients with HG-NECs. Conclusions Therefore, SOX11 is a useful complementary transcriptional NE marker for diagnosis and differential diagnosis of SCLC and LCNEC.

Characterisation of TRIM46 autoantibody-associated paraneoplastic neurological syndrome

ObjectivesTo report the expanded neurological presentations and oncological associations of tripartite motif-containing protein 46 (TRIM46)-IgG seropositive patients.MethodsArchived sera/cerebrospinal fluid (CSF) were evaluated by tissue-based immunofluorescence assay to identify patients with identical axon initial segment (AIS)-specific staining pattern. Phage immunoprecipitation sequencing (PhIP-Seq) was used to identify the putative autoantigen.ResultsIgG in serum (17) and/or CSF (16) from 25 patients yielded unique AIS-specific staining on murine central nervous system (CNS) tissue. An autoantibody specific for TRIM46 was identified by PhIP-Seq, and autoantigen specificity was confirmed by transfected COS7 cell-based assay. Clinical information was available for 22 TRIM46-IgG seropositive patients. Fifteen were female (68%). Median age was 67 years (range 25–87). Fifteen (68%) patients presented with subacute cerebellar syndrome (six isolated; nine with CNS accompaniments: encephalopathy (three), brainstem signs (two), myelopathy (two), parkinsonism (one)). Other phenotypes included limbic encephalitis (three), encephalopathy with/without seizures (two), myelopathy (two). Eighteen (82%) had cancer: neuroendocrine carcinomas (9; pancreatic (3), small-cell lung (4), oesophagus (1), endometrium (1)), adenocarcinomas (6; lung (2), ovarian (2), endometrial (1), breast (1)), sarcoma (2) and gastrointestinal tumour (1). Neurological symptoms in three followed immune checkpoint inhibitor (ICI) administration.ConclusionsThis study supports TRIM46-IgG being a biomarker of paraneoplastic CNS disorders and expands the neurological phenotypes, oncological and ICI-related adverse event associations.

Bilateral Neuroendocrine Carcinoma of Breast: A Case Report

Primary neuroendocrine carcinomas of the breast are rare of all breast carcinomas. They may be welldifferentiated, poorly differentiated, or invasive breast cancers with neuroendocrine differentiation. They are staged and treated similarly to conventional breast cancer. Herein, we report a case of invasive ductal carcinoma with neuroendocrine differentiation of the breast in a 73 years female with a history of breast lump initially in the lower inner quadrant of left breast and a month later, similar lump at the same site in right breast. Patient underwent Modified Radical Mastectomy bilaterally followed by adjuvant chemotherapy based on Carboplatin and Etoposide regimen.

Clinical Features And Prognosis of Advanced Intra- And Extra-Pulmonary Neuroendocrine Carcinomas

Objective: We analyzed the clinical features and prognosis of advanced intra- and extra-pulmonary neuroendocrine carcinomas (NECs) in order to provide further guidance for the clinical treatment of small-cell lung cancer, which is a type of advanced intrapulmonary NECs. Methods: The clinical data and survival of 123 patients with advanced intra- and extra-pulmonary NECs in the Fujian Medical University Union Hospital, Fujian Province, China, between January 2013 to November 2019 were collected. We retrospectively analyzed the corresponding clinical diagnosis and treatment, and explored the relevant factors affecting the survival prognosis of patients with intra- and extra-pulmonary NECs. Results: The data of 123 patients were collected. There were 90 cases of intra-pulmonary NECS (including 81 cases of small-cell lung cancer, SCLC), 25 cases of extra-pulmonary NECs involving in the gastrointestinal tract, and 8 cases of extra-pulmonary NECs in other regions. The median overall survival (OS) of intra-pulmonary NECs was 13.53 months, of which the median OS of SCLC was 12.97 months, and the median OS of other intra-pulmonary NECs was 27.07 months. The median OS of extra-pulmonary NECs in the gastrointestinal tract was 9.42 months, and the OS of extra-pulmonary NECs in the other regions was 8.69 months. The median OS of intra-pulmonary NECs was significantly longer than that of the extra-pulmonary NECs in the gastrointestinal tract and in the other regions (P < 0.05). Multivariate analysis showed that age, liver metastasis, number of cycles of first-line chemotherapy, and chest radiotherapy were risk factors affecting OS in patients with NECs (P < 0.05). Conclusions: The survival of intra-pulmonary NECs was significantly longer than that of extra-pulmonary NECs of the gastrointestinal tract and in other regions. However, patients with advanced intra- and extra-pulmonary NECs who were older and had liver metastases had a poorer prognosis. Multi-disciplinary treatments such as multi-cycle chemotherapy and combination of chemotherapy and radiotherapy should play an important role in prolonging the survival of NECs.