Neuroendocrine Carcinoma Of Esophagus Research Articles

Long-term survival after conversion surgery for an esophageal neuroendocrine carcinoma: a case report

BackgroundEsophageal neuroendocrine carcinomas (NECs) are extremely rare. Published information on their clinical features, pathological findings, and prognosis is lacking. The optimal treatment for esophageal NECs has not yet been determined because they appear extremely malignant histologically and have a poor prognosis. We here report on a patient with an esophageal NEC who was successfully treated with multidisciplinary therapies.Case presentationThe patient, a 47-year-old man, was admitted to our hospital with dysphagia and weight loss and an ECOG performance status of 3–4. Upper endoscopy showed a large circumferential neoplasm at the esophagogastric junction. Computed tomography showed lymph node metastases around the left gastric artery. Echocardiography raised a suspicion of invasion of the left atrium. Histopathological examination of biopsy tissue revealed diffuse proliferation of small atypical cells resembling naked nuclei with extensive necrosis and degeneration. The cells showed positive staining for CD56, chromogranin A, and synaptophysin on immunohistochemical analysis. Ki67 was positive in over 90% of cells. He was diagnosed with an esophageal NEC that had infiltrated the left atrium; his cancer was therefore inoperable. Because of his poor overall condition, palliative radiotherapy (30 Gy in 15 fractions) was administered, accompanied by nutritional management. This was followed by four courses of chemotherapy with carboplatin plus etoposide, after which the primary tumor and locoregional lymph node metastases were found to have shrunk. Thoracoscopic- and laparoscopic-assisted McKeown esophagectomy were performed. The postoperative pathological diagnosis was NEC pT3pN0M0 Stage II. The patient had a good postoperative course and received two courses of postoperative adjuvant chemotherapy (carboplatin plus etoposide). Currently, 3 years after commencing treatment, there is no evidence of recurrence.ConclusionsAs mentioned above, there is no established treatment regime for esophageal NEC, and the benefits of conversion surgery are unknown. Our patient achieved long-term recurrence-free survival after radiation therapy, chemotherapy, and surgery for an esophageal NEC with left atrial invasion and multiple lymph node metastases. Conversion surgery for esophageal NECs that respond to chemotherapy may contribute to long-term survival.

Neuroendocrine carcinomas of the esophagus: clinicopathological and immunohistochemical features of 43 cases

BackgroundNeuroendocrine carcinomas (NECs) of the esophagus are extremely rare and poorly understood. This study aimed to delineate the clinicopathological and immunohistochemical features of esophageal NECs using a retrospective survey.MethodsPatients with histologically proven esophageal neuroendocrine carcinomas (NECs) were recruited from Zhongshan Hospital, Fudan University, China, between 2006 and 2016. Clinical, endoscopic, pathological, and immunohistochemical data were collected retrospectively.ResultsOf 43 patients with NEC, older male patients were predominant. In total, 93.0% of the tumor masses were located in the middle or lower esophagus. Twenty-nine (67.4%) and 22 (51.2%) cases showed ulceration and esophageal stenosis, respectively. The average index of Ki-67 staining was 67.1% ± 21.4% with positive immunostaining for CD56 (88.4%), chromogranin A (51.2%), and synaptophysin (72.1%). Small cell carcinomas accounted for 95.3% of cases, and 16.3% of patients had mixed components with adenocarcinoma or squamous cell carcinoma.ConclusionEsophageal NECs are rare and mainly affect men in their sixties or seventies. They show a similar endoscopic appearance to squamous cell carcinoma or adenocarcinoma and present with a proliferative mass with stenosis or ulcers. Therefore, esophageal NECs are difficult to diagnose by endoscopy. Esophageal NECs can be mixed with other subtypes of neoplasms, such as adenocarcinoma and squamous cell carcinoma. In addition to chromogranin A, synaptophysin, and CD56, NSE, S100, and CKpan might be candidate biomarkers to diagnose esophageal NECs. Overall, we provide new insights into the biology of esophageal NECs.

Analysis of the Clinicopathological Characteristics, Prognosis, and Lymphocyte Infiltration of Esophageal Neuroendocrine Neoplasms: A Surgery-Based Cohort and Propensity-Score Matching Study.

Esophageal neuroendocrine neoplasms (E-NENs) are a rare and poorly reported subtype of esophageal carcinoma. We analyzed the differences in clinicopathological features, prognosis, and tumor-infiltrating lymphocytes (TILs) between E-NENs and esophageal squamous cell carcinoma (ESCC). A total of 3620 patients who underwent esophagectomy were enrolled retrospectively. The study cohort was divided into two groups (E-NENs and ESCC) through propensity-score matching, and the prognosis and TILs were compared between the two groups. The TILs were assessed using tumor specimens (including six cases of ESCC, six cases of neuroendocrine carcinomas [NECs], and six cases of mixed neuroendocrine-non-neuroendocrine neoplasms [MiNENs]). E-NENs accounted for 3.0% (107/3620) of cases, among which there were just 3 neuroendocrine tumor cases, 51 NEC cases, and 53 MiNENs cases. After matching, esophageal neuroendocrine carcinomas (E-NECs) showed both poorer 5-year overall survival (OS; 35.4% vs. 54.8%, p = 0.0019) and recurrence-free survival (RFS; 29.3% vs. 48.9%, p < 0.001) compared with ESCC. However, the differences were not prominent in the subgroup with stage I. No significant survival benefit was observed for E-NECs with multimodal therapy. Multivariate analysis demonstrated that E-NECs are an independent risk factor for OS and RFS. In the exploratory analysis, E-NECs were associated with less infiltration of immune cells compared with ESCC. E-NECs are significantly associated with a poorer prognosis than ESCC except for early-stage disease. The fewer TILs within the tumor microenvironment of E-NECs compared with ESCC results in weaker anti-tumor immunity and may lead to a poorer prognosis.

Analysis of Clinicopathological Characteristics of 88 Cases with Secondary Neoplasms of the Thyroid Gland

To analyze the clinicopathological characteristics of secondary neoplasms of the thyroid gland (SNTGs). SNTG Patients who had pathology diagnosis of SNTGs between January 2010 and December 2019 at West China Hospital, Sichuan University were retrospectively enrolled. The SNTG cases were divided into two groups, a local invasion group and a distant metastasis group, and their clinical features were reviewed. The study involved 88 patients, with a female-to-male (F/M) ratio of 1/3 and an average age of 56 years. The local invasion group consisted of 72 patients (F/M, 1/8) who had the following types of tumors: 65 had squamous cell carcinomas (45 originated from larynx and 10 from laryngopharynx), 4 had adenoid cystic carcinomas, 1 had neuroendocrine carcinoma of esophagus, 1 had giant cell tumor, and 1 had type B3 thymoma. The distant metastasis group consisted of 16 patients (F/M, 7/1), all with previously confirmed history of malignancies of sites distant from the thyroid. Their primary tumor types were as follows, 6 had breast carcinomas, 5 had lung adenocarcinomas, 2 had nasopharyngeal non-keratinizing carcinomas, 1 had clear cell renal carcinoma, 1 had colon adenocarcinoma, and 1 had cervical squamous cell carcinoma. Given that SNTGs are generally rare, the local invasion cases were predominantly squamous cell carcinomas that mainly originated from the larynx and the patients usually had no previous history of malignancy, while the distant metastasis cases often had a corresponding history of malignancies, consisting mainly of breast carcinoma and lung carcinoma.

Clinical characteristics, prognostic factors, and survival trends in esophageal neuroendocrine carcinomas: Apopulation-based study.

Esophageal neuroendocrine carcinoma (ENEC) is an extremely rare type of malignancy. Clinical data of ENEC are limited to case reports and case series. More information is needed on its clinical feature, management, and prognosis. This study collected information of ENEC patients diagnosed pathologically from 2010 to 2018. Data including demographic information, clinical features, and survival trends were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Statistical analyses were performed with STATA/SE 15.1, SPSS 25.0, and GraphPad Prism 8. A total of 283 ENEC patients were included in this study. The small-cell and large-cell subtypes of ENEC possess similar clinical features. The lower third of the esophagus (58%) was the most common location of ENEC. At the time of diagnosis, most ENEC patients were AJCC 7th stage IV (48.1%). Metastasis occurred in more than half of the ENEC patients (53.4%), and the most common metastatic site was the liver (37.1%). Compared with poorly differentiated esophageal squamous cell carcinoma (ESCC), another aggressive malignancy of the esophagus sometimes confused with ENEC because of similar histological features, our study showed differences in tumor location and metastatic rate, but similar poor survival rates. Multivariate survival analysis showed that ENEC located at the middle third of esophagus (p= 0.013), "Brain metastasis" (p= 0.019), and "Liver metastasis" (p< 0.001) were independent predictors of worse outcomes. "Surgery" (p= 0.003), and "Chemotherapy" (p< 0.001) were associated with better survival. A significant proportion of patients with newly diagnosed ENEC presented with metastatic disease. Predictors of poor survival included tumor location, brain metastasis, and liver metastasis. ENEC and poorly differentiated ESCC share certain histological features, but differ in tumor location and metastatic rate. Yet, no standard treatment strategy has been established, but surgery and chemotherapy were related to better outcomes.

The clinicopathologic features and prognosis of esophageal neuroendocrine carcinomas: a single-center study of 53 resection cases

BackgroundEsophageal neuroendocrine carcinomas (NECs) are exceedingly rare and poorly understood. The aims of the retrospective study were to delineate the clinicopathologic features and prognosis of patients with the disease.MethodsWe performed a retrospective study containing 53 patients of esophageal NECs in our center from 2002 through 2018. Patients were assigned to the pure esophageal NECs group and the esophageal NECs mixed with squamous carcinoma and/or esophageal adenocarcinoma (MiNECs) group. Demographic, clinical, pathologic and prognostic factors were recorded and analyzed.ResultsOf the 53 patients, elderly male patients were predominant. Dysphagia was the most common symptom (45/53, 84.9%). Most tumors were centered in the middle esophagus (36/53,67.9%).Ulcerated appearance was frequently seen in the pure NECs (56.8%), and the tumors in the MiNECs group mostly represented elevated types (57.9%). Synaptophysin (38/45, 84.4%), chromogranin A (21/38, 55.3%) and CD56(23/27, 85.2%) have been proven to be positive markers for NECs. Most patients (46/53, 86.8%) received surgery combined with chemotherapy. Though the pathologic stages were alike (P = 0.129), the median survival time was 3.53 years for the pure NECs group and 7 years for the MiNECs group. In multivariate analysis, pathologic stage (RR = 1.938, P = 0.045) and age (RR = 2.410, P = 0.028) were independent prognostic factors for patients with MiNECs. The prognosis of patients with pure NECs was independent from any factors.ConclusionsCareful endoscopic examination could help distinguish pure NECs from MiNECs. NECs were aggressive, but a relative better prognosis for patients with MiNECs. Surgery should be performed if applicable, and chemotherapy might be helpful.

1714 A Case of a Primary Large Cell Neuroendocrine Carcinoma of the Esophagus Disguised as a Food Impaction

INTRODUCTION: Neuroendocrine carcinomas (NECs) are defined epithelial neoplasms with predominant neuroendocrine differentiation. They primarily arise from the gut and bronchopulmonary systems with the possibility of distant metastasis. We present a case of an esophageal neuroendocrine neoplasm with unique endoscopic/radiographic features on presentation disguised as a food impaction. CASE DESCRIPTION/METHODS: A 50-year-old Caucasian male with past medical history of tobacco dependence; presented to the ED with complaints of solid food dysphagia for 1.5 months with unintentional weight loss of 15 lbs and intractable hiccups. On arrival, he was hemodynamically stable. Physical exam was unremarkable. Laboratory testing revealed mild normocytic anemia of 12.3, otherwise unremarkable. An upper endoscopy was performed revealing a large amount of meat in the mid-esophagus; however, after further manipulation there appeared to be bleeding from the mucosa (Figure 1). Upon closer inspection, a mass originating from the lateral esophageal wall was caked with food debris giving it the appearance of meat. CT Chest was performed showing a large heterogenous esophageal mass (8.1 cm v 5.7 cm) extending from the mid-esophagus to the GE junction with no evidence of direct invasion (Figure 2). Biopsies returned positive for large cell neuro-endocrine carcinoma with diffuse synaptophysin and Ki67 positivity. PET-CT performed as outpatient showed prominent peri-gastric lymphadenopathy. EUS was attempted but failed due to inability to pass the ultrasound scope. CT surgery subsequently performed a McKeown transthoracic esophagectomy for definitive therapy as outpatient. He recovered well from the procedure with positive radial margins and lymph nodes on pathology and is now undergoing adjuvant radiation and chemotherapy. DISCUSSION: Esophageal NEC is a rare entity with a generally dismal prognosis when high-grade. A study out of a large volume, tertiary center reported approximately 40 cases over a 20-year period. Given the sparsity of esophageal NECs, most studies are retrospective case series and are from outside the USA. It is reported that esophageal NECs represent only 0.4-1.4% of the gastrointestinal NECs a majority of which arise from the mid-esophagus. To our knowledge, there is no reports of a single case with similar endoscopic and radiographic findings which makes it unique. There is also limited data reported on the endoscopic/phenotypic appearance of large cell neuroendocrine carcinomas of the esophagus.

Frequent and Specific Involvement of Changes of the p16-RB Pathway in Esophageal Neuroendocrine Carcinoma.

This study investigated the immunohistochemical expression of retinoblastoma (RB) protein and p16 protein in 10 neuroendocrine carcinomas (NECs), in comparison to two mixed-type NECs; 28 squamous cell carcinomas (SCCs), and 12 carcinosarcomas (CSs) from patients with esophageal cancer. Immunohistochemical staining was performed using the avidin-biotin complex detection method. The staining was evaluated as diffusely positive, heterogeneous (in 5-95% of tumor cells), or diffusely negative. The combination of a diffuse loss of RB and the diffuse overexpression of p16, which is found in highly aggressive malignant tumors and is considered to convincingly suggest changes in the p16-RB pathway, was found in all NECs (10/10). In contrast no mixed-type NECs, one SCC and one CS showed this finding. Coexisting intraepithelial carcinoma was detected in seven NECs and only one lesion showed the combination of diffuse RB loss and p16 overexpression. These data suggest that changes in the p16-RB pathway were universally and specifically involved in the development and invasion of esophageal NECs and that it may be a useful diagnostic marker and a potential therapeutic target.

Neuroendocrine carcinoma of the esophagus: Clinicopathological and immunohistochemical features of 14 cases

BackgroundNeuroendocrine carcinoma (NEC) of the esophagus is a rare and highly aggressive disease but the biological features are poorly understood. The objective of this study was to analyze the clinicopathological and immunohistochemical features of NEC of the esophagus.MethodsFourteen patients diagnosed with NEC of the esophagus from 1998 to 2013 were included in this study. Clinicopathologic features, therapeutic outcomes and immunohistochemical results were analyzed.ResultsEleven out of 14 cases showed protruding or localized type with or without ulceration. Only three patients were negative for both lymph node and organ metastasis and seven cases were positive for metastases to distant organs and/or distant lymph nodes. Of the six patients with limited disease (LD), three patients were treated by surgery. Three patients with LD and seven patients with extensive disease (ED) were initially treated with chemotherapy, except for one who underwent concurrent chemo-radiotherapy due to passage disturbance. The median survival of patients with LD was 8.5 months, whereas that of patients with LD was 17 months. Among the 14 cases, 12 cases (83.3%), 13 cases (91.7%) and 12 cases (83.3%) showed positive immunostaining for choromogranin A, synaptophysin and CD56, respectively. Nine of 14 cases (64.2%) presented positive staining for c-kit and most (8/9, 88%) simultaneously showed p53 protein abnormality. Two cases were negative for c-kit and p53, and positive for CK20.ConclusionConsistent with previous reports, the prognosis of NEC of esophagus is dismal. From the results of immunohistochemical study, NEC of esophagus might be divided into two categories due to the staining positivity of c-kit and p53. This study provides new insight into the biology of NEC of the esophagus.

Neuroendocrine carcinoma of the esophagus: Report of a case and review of the literature

Esophageal neuroendocrine carcinomas are rare, aggressive and have a poor prognosis. Combined therapy using chemotherapy, radiotherapy and/or surgery appear effective for them. Upper gastrointestinal endoscope of a 65-year-old male revealed a localized ulcerative lesion in the middle esophagus. Histology of biopsy specimens indicated a neuroendocrine carcinoma. A computed tomography showed an esophageal tumor with enlarged mediastinal lymph nodes. The patient was administered neoadjuvant chemo-therapy consisting of 5-fluorouracil and cisplatin, which led to partial response. Subtotal esophagectomy with three-field lymphadenectomy was performed. Pathologically, the tumor was 25 mm and infiltrated the proper muscle layer. The tumor cells were arranged in microtubular structures, with small and round cells containing scanty cytoplasm, and exhibited intense mitosis 51/10 HPF. They were positive for synaptophysin and chromogranin A, and Ki-67 labeling index was 70% - 80%. These findings led to the diagnosis of neuroendocrine carcinoma of small cell type. The patient was administered adjuvant chemotherapy using cisplatin and CPT-11, and he is now alive disease-free at the time of this writing.

術後早期に肝転移を来した食道神経内分泌癌の１例

症例は52歳の男性で, 主訴は嚥下困難. 上部消化管内視鏡検査で切歯列より32～36cmに境界明瞭, 表面結節状の隆起性病変を認め, 生検により神経内分泌癌と診断された. 胃小彎リンパ節腫大を認めたが, 遠隔転移, 縦郭リンパ節腫大はなく, 開胸下食道切除術を施行した. 病理組織学的検査所見で深達度はpSM, ie (+), ly1, v0, pIM0, pN2 (#7)であった. 免疫組織学的に腫瘍は, 神経内分泌マーカーCD56, NSE, S-100蛋白, chromogranin A, Synapto-physinが陽性であった. 術後は約1か月半で多発肝転移, 腹腔内リンパ節再発を認め, 手術から約2か月後に死亡し, 高悪性度の腫瘍と考えられた. 腫瘍形態の詳細な観察では, 高分化・上皮様部位と, 低分化・肉腫様の部位が混在し, ATBF1は前者では核主体, 後者では細胞質主体の染色性を示した.