Primary Esophageal Small Cell Carcinoma Research Articles

The Survival and Prognosis Characteristics of Primary Esophageal Small-Cell Carcinoma.

Objective To comprehensively explore the survival characteristics of primary esophageal small-cell carcinoma (PSCCE) and identify the main factors affecting the prognosis. Methods The clinical and follow-up data of PSCCE patients admitted to the Fourth Hospital of Hebei Medical University from 2006 to 2010 were retrospectively analyzed. The primary endpoint was five-year survival. Survival curves were drawn using the Kaplan-Meier method, and log-rank test was used to compare the differences in survival rates among the groups. Cox regression models were used to analyze prognostic factors. Results A total of 119 eligible patients were retrieved. Median survival was 27 months (3-100 months). Changes in overall survival (OS) in PSCCE patients were associated with TNM stage (P = 0.007), T stage (P = 0.049), and lymph node metastasis (P = 0.004). When TNM was in stage I-IIb, lymph node metastasis (P = 0.003) or combined adjuvant therapy (P = 0.004) was an independent factor affecting OS. Survival analysis showed that TNM staging had no predictive value for 5-year survival time or disease-free survival (DFS) of PSCCE (P > 0.05). Conclusion TNM stage, T stage, and lymph node metastasis were related to the survival of patients. Negative lymph node metastasis and treatment are independent prognostic factors in PSCCE TNM stage I-IIb patients.

Novel nomogram predicting cancer-specific survival and overall survival in patients with primary esophageal small-cell carcinoma: A surveillance, epidemiology, and end results-based study.

Small-cell carcinoma is a relatively infrequent pathological variety of esophageal cancer. In this study, a novel nomogram model was developed to evaluate the cancer-specific survival (CSS) and overall survival (OS) of patients with primary esophageal small-cell carcinoma (ESmCC). In total, 502 patients with primary ESmCC were identified based on data from 1973 to 2015 retrieved from the surveillance, epidemiology, and end results database. Clinical characteristics such as age at diagnosis, gender, race, site, tumor stage, surgery, radiotherapy, and chemotherapy were included for multivariate logistic analyses to predict CSS and OS. Nomogram models for the prediction of CSS and OS in ESmCC patients were tested with the concordance index (C-index) method and calibration curves. From our multivariate analyses, race, stage, chemotherapy, and radiotherapy, but not surgery, were significantly associated with the CSS of ESmCC patients, while age at diagnosis, stage, chemotherapy, and radiotherapy were significantly associated with their OS. Nomograms were developed using age at diagnosis, race, gender, stage, surgery, radiotherapy, and chemotherapy to predict the two survival measures; these nomograms were verified as accurate in predicting OS and CSS in ESmCC patients, with C-index values of 0.736 and 0.731, respectively. By utilizing easily accessible clinicopathological information, we established a simple but useful tool for predicting the CSS and OS of ESmCC patients that could help to make personalized clinical decisions for patients with this rare malignancy. Cancer-specific survival, esophageal small-cell carcinoma, nomogram, overall survival, surveillance, epidemiology, and end results.

Tumor-Infiltrating Immune Cells and PD-L1 as Prognostic Biomarkers in Primary Esophageal Small Cell Carcinoma.

Primary esophageal small cell carcinoma (PESCC) is a weakly prevalent but lethal malignancy with early metastasis and a poor prognosis. Currently, neither effective prognostic indicators nor curative therapies are available for PESCC. Immunotherapy has now evolved into one of the most promising therapies for cancer patients. Tumor-infiltrating immune cells which are integral to the tumor immune microenvironment (TIME) are recognized as highly important for prognosis prediction, while the responsiveness to immune checkpoint blockade may be subject to the features of TIME. In this study, we aim to identify the TIME and provide indication for the applicability of immune checkpoint therapy in PESCC. We found that PD-L1 expression was detected in 33.33% (27/81) of all the patients, mostly exhibiting a stroma-only pattern and that it was positively associated with tumor-infiltrating immune cells (CD4+, CD8+, and CD163+). In 74.07% of PD-L1-positive specimens, PD-L1+CD163+ cells were colocalized more with CD4+ than CD8+ T cells. 83.95% (68/81) of all the specimens were infiltrated with more CD4+ than CD8+ T cells. Further analysis showed FoxP3+ Tregs constituted 13-27% of the total CD4+ T cell population. The Kaplan-–Meier analysis indicated several factors that contribute to poor survival, including negative PD-L1 expression, rich CD4 expression, rich FoxP3 expression, a low CD8/CD4 ratio, and a high FoxP3/CD8 ratio. A nomogram model was constructed and showed good performance for survival prediction. These results highlight that a suppressive TIME contributes to poor survival of patients with PESCC. TIME analyses might be a promising approach to evaluate the possibility and effect of immune checkpoint-based immunotherapeutics in PESCC patients.

Treatment and prognostic analysis of patients with primary esophageal small-cell carcinoma

Objective: The study aimed to analyze the clinicopathological features, treatment, and prognosis factors of primary esophageal small-cell carcinoma (PESC). Methods: The clinical records and follow-up data of 100 patients with PESC were collected, and the clinicopathological features and treatments were examined. Log-rank test and Cox regression model were performed to identify the independent prognostic factors. Results: Progressive dysphagia, weight loss, and abdominal pain were the most common initial symptoms in the 100 patients with PESC. The primary tumor site mainly occurred in the middle of the chest (51%, 51/100), and the ulcer type was the most common under gastroscope (31%, 31/100). One or more positive markers of epithelial origin were present in all of the enrolled patients. At the time of diagnosis, 80 cases had limited disease (LD) and 20 cases had extensive disease (ED). The 1-, 3-, and 5-year survival rates of PESC patients were 57.0%, 18.0%, and 11.0%, respectively, with a median survival time (MST) of 13.8 months. In all PESC patients, multivariate Cox regression analysis indicated that the significant prognostic factors included the lesion length (OR=2.661, P<0.001), TNM staging (OR=1.464, P=0.016), and treatment methods (OR=0.333, P<0.001). Besides, in patients with LD, the lesion length (OR=2.638, P=0.001) and treatment methods (OR=0.285, P<0.001) were independent prognostic factors. The MST of patients in surgery + chemotherapy group (21.6 months) was longer than that of the surgery only group (8.3 months, P=0.021), while patients in surgery+ chemotherapy+ radiotherapy group were also associated with a longer MST than the chemotherapy + radiotherapy group (31.0 months, 9.8 months, respectively; P<0.001). Conclusions: PESC is a rare esophageal malignant tumor with poor prognosis. Our findings reveal that the lesion length, TNM staging, and treatment method are independent prognostic factors for PESC patients. Moreover, surgery-based comprehensive treatments may prolong the survival of patients with LD.

Curative effect analysis of different clinical characteristics and treatment modalities for primary esophageal small cell carcinoma

Objective To analyze the efficacy of different clinical characteristics and treatment modalities for patients with primary esophageal small cell carcinoma (PESC), and to find out the prognostic factors, and provide reference for clinical treatment decision. Methods Patients with PESC who were treated at Shandong Cancer Hospital Affiliated to Shandong University from January 2008 to May 2017 were retrospectively enrolled. The clinical features were collected. Their disease progression time and survival status were determined by follow-up, and the follow-up ended in October 2017. Data analysis was performed using SPSS 25.0 software, and GraphPad Prism 7.0 was used for mapping. Survival analysis was performed by Kaplan-Meier me-thod, and log-rank test was used to compare the differences in survival curves of each group. Factors with significant differences in univariate analysis were included in the Cox multivariate survival analysis. ROC curve was used to verify the sensitivity and specificity of the model. Results A total of 83 PESC patients with a complete follow-up were included in the study, including 68 males and 15 females. The average age was 61.93 years old (41-82 years old). The median progression-free survival (PFS) was 9.1 months (1.0-60.0 months) and the median overall survival (OS) was 26.1 months (1.8-60.0 months). Cox multivariate survival analysis showed radiotherapy or not (HR=0.321, 95%CI: 0.184-0.559, P<0.001) and chemotherapy cycles (HR=0.841, 95%CI: 0.737-0.960, P=0.010) were independent prognostic factors for PFS. The Veterans Administration Lung Study Group (VALSG) staging (HR=3.050, 95%CI: 1.606-5.794, P=0.001), radiotherapy or not (HR=0.312, 95%CI: 0.174-0.560, P<0.001), and chemotherapy cycle (HR=0.711, 95%CI: 0.601-0.842, P<0.001) were independent predictors of OS. The ROC curve showed that the sensitivity and specificity of the PFS prediction model were 78.26% and 73.33%, and the sensitivity and the specificity of the OS prediction model were 80.00% and 58.49%. Conclusion VALSG staging is an independent predictor of PESC survival. Comprehensive therapy based on radiotherapy and chemotherapy can improve disease control, reduce metastasis, and improve survival. Key words: Treatment effectiveness; Prognosis; Comprehensive treatment; Primary esophageal small cell carcinoma

Abstract 5126: Establishment of an esophageal small cell carcinoma cell line (TYUC-1)

Abstract Background: Small cell carcinoma of the esophagus is rare and its prognosis is extremely poor. However, there is currently no in vitro model of this disease. Methods: After obtaining written informed consent, we obtained a tumor from a 56-year-old female patient with esophageal small cell carcinoma in 2009 and transplanted it into a Severe Combined Immuno Deficiency (SCID) mouse. After successful transplantation, a tumor from the back of this mouse was minced with a sharp scissors without enzymes and was cultured in Ham F12/DMDM supplemented with 5% fetal bovine serum. Results: Culture cells grew as adherent cells during the initial culture phase and gradually grew as floating aggregated cells. We carefully maintained these floating cells and transferred them without enzymes. These cells could passage to another flask with a split ratio of 1/10. We named these cells “TYUC-1”, and passaged them more than 85 times. The population doubling-time of TYUC-1 was approximately 30 hours. The G-band karyotype confirmed that these cells had a human origin. These cells could be transplanted to SCID mice with the same histological features of primary esophageal small cell carcinoma, and were shown to express TrkA, NGF, NSE, FGFRL1, p53, CD56, ALDH1A1, and CD44, but not CD133. A cDNA array also revealed that 9 genes were overexpressed while the expression of 33 genes was significantly lower than that in 28 esophageal squamous cell carcinoma (ESCC) cell lines. Whole exome sequencing revealed that TYUC-1 had TP53, PIK3CA, KMT2D, CACNA1H, NCOR1 and HRAS mutations. Furthermore, TYUC-1 had mutations in 128 genes, whereas 28 ESCC cell lines had no mutations in these genes. Conclusions: We newly established TYUC-1 cells that exhibited neuroendocrine characteristics and expressed several stem cell-related molecules. These cells may be useful for understanding the characteristics of esophageal small cell carcinoma. Citation Format: Yutaka Shimada, Tomoyuki Okumura, Yoshinori Takei, Kazuaki Watanabe, Akira Hirasawa, Arito Yamane, Masahiko Nishiyama, Takuya Nagata, Kazuhiro Tsukada, Kazuharu Shimizu. Establishment of an esophageal small cell carcinoma cell line (TYUC-1). [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5126. doi:10.1158/1538-7445.AM2015-5126

Dysregulation of PAK1 Is Associated with DNA Damage and Is of Prognostic Importance in Primary Esophageal Small Cell Carcinoma.

Primary esophageal small cell carcinoma (PESCC) is a rare, but fatal subtype of esophageal carcinoma. No effective therapeutic regimen for it. P21-activated kinase 1 (PAK1) is known to function as an integrator and an indispensable node of major growth factor signaling and the molecular therapy targeting PAK1 has been clinical in pipeline. We thus set to examine the expression and clinical impact of PAK1 in PESCC. The expression of PAK1 was detected in a semi-quantitative manner by performing immunohistochemistry. PAK1 was overexpressed in 22 of 34 PESCC tumors, but in only 2 of 18 adjacent non-cancerous tissues. Overexpression of PAK1 was significantly associated with tumor location (p = 0.011), lymph node metastasis (p = 0.026) and patient survival (p = 0.032). We also investigated the association of PAK1 with DNA damage, a driven cause for malignancy progression. γH2AX, a DNA damage marker, was detectable in 18 of 24 (75.0%) cases, and PAK1 expression was associated with γH2AX (p = 0.027). Together, PAK1 is important in metastasis and progression of PESCC. The contribution of PAK1 to clinical outcomes may be involved in its regulating DNA damage pathway. Further studies are worth determining the potentials of PAK1 as prognostic indicator and therapeutic target for PESCC.

Treatment and Prognosis of 73 Cases With Limited-Stage Primary Esophageal Small Cell Carcinoma: Mesothelioma, Thymic Malignancies, and Other Thoracic Malignancies

Treatment and Prognosis of 73 Cases With Limited-Stage Primary Esophageal Small Cell Carcinoma: Mesothelioma, Thymic Malignancies, and Other Thoracic Malignancies

Metachronous Primary Distal Esophageal Small Cell Carcinoma and Adenocarcinoma Arising From the Same Site Inside a Barrett’s Segment

Introduction: Small cell carcinoma of the esophagus is rare and represents around 1% of esophageal cancer cases. Synchronous primary small cell carcinoma and adenocarcinoma of the esophagus in the same lesion are extremely rare, with metachronous presentations of these tumors within a Barrett’s segment not previously reported. We herein describe a case of a metachronous presentation of an adenocarcinoma arising 14 months later from the same site of a distal esophageal primary small cell carcinoma in remission within a Barrett’s segment. Case Report: A 55-year-old white male presented with dysphagia and unintentional weight loss. Esophagogastroduodenoscopy (EGD) showed an ulcerated friable mass in the distal esophagus at 35 cm from the incisors and extended to the level of the gastroesophageal (GE) junction at 40 cm within a C11M14 Barrett’s segment that extended from 26-40 cm from the incisors. Biopsies from the mass showed highgrade neuroendocrine carcinoma, small cell type. There were no lung masses or any distant metastases on PET/CT. On endoscopic ultrasound (EUS), the lesion measured 3.08 x 3.12 cm in maximum width and depth with breakthrough to the adventitia. Four malignant-appearing para-esophageal lymph nodes were identified. TNM staging was T3N2M0. The patient received radiotherapy and chemotherapy with VP16 and cisplatin. He improved clinically and repeat PET/CT showed a drop in SUV values with no distal metastasis. Repeat EGD with EUS at 6 and 9 months after diagnosis were showing the same Barrett’s segment in addition to thickening of the mucosa from 36 to 39 cm from the incisors within the area of the previously identified tumor, with significant improvement in the appearance of the lesion. Biopsies from the Barrett’s segment including the site of the previously described lesion were showing intestinal metaplasia without dysplasia. However,14 months after diagnosis, biopsies came back positive for adenocarcinoma within the ulcerating lesion at 38-39 cm in addition to high-grade dysplasia at multiple locations within the Barrett’s segment. The patient subsequently underwent Ivor Lewis esophagectomy. The surgical specimen had negative margins with focal residual adenocarcinoma at the GE junction, invading only the muscularis mucosa, with greatest dimension of 0.1 cm. Pathologic staging was pT1aN0. Twenty months after diagnosis with small cell carcinoma, and then with adenocarcinoma at the same site, the patient is alive and recovering from post-operative complications. Conclusion: This case provides important additional evidence to the presence of totipotent cells within Barrett’s metaplasia that are capable of multidirectional differentiation causing multiple types of carcinoma.

Treatment and Prognosis of 73 Cases With Limited-Stage Primary Esophageal Small Cell Carcinoma

Treatment and Prognosis of 73 Cases With Limited-Stage Primary Esophageal Small Cell Carcinoma

Detailed Analysis of Prognostic Factors in Primary Esophageal Small Cell Carcinoma

Primary small cell carcinoma of the esophagus (SCCE) is characterized as highly aggressive with a poor prognosis. To identify potential prognostic factors and to assess the role of surgical procedures, chemotherapy, and radiotherapy for SCCE, we retrospectively analyzed patients with SCCE from three large institutions in China. All of the SCCE patients between 1998 and 2012 were identified from three clinical databases of the Sun Yat-Sen University Cancer Center, Peking Union Cancer Hospital and Shantou Cancer Hospital. Potential prognostic factors were analyzed with univariate analysis and a Cox regression model. Subgroup analysis based on the 2002 American Joint Committee on Cancer staging system for esophageal cancer was applied to examine the effect of treatment on survival. In patients with stage I/II SCCE, 85% underwent operations and showed improved survival (median survival time [MST] 29 vs 17.4 months, p= 0.082). However, chemotherapy did not further improve survival. In patients with stage IIB/III SCCE, chemotherapy, instead of operation, improved survival (MST 13.0 vs 6.1 months, p= 0.003), and radiotherapy resulted in improved survival. In stage IV patients, chemotherapy improved survival (MST 12.5 vs 4.0 months, p < 0.001), and chemotherapy combined with radiotherapy was superior to chemotherapy alone (MST 13.2 vs 8.9 months, p= 0.014). Surgical procedures alone can be recommended for stage I/IIA patients. In patients with stage IIB disease or above, chemotherapy should be the main treatment approach, and chemotherapy combined with radiotherapy tended to improve survival.

Pattern of lymph node metastasis in limited-stage primary esophageal small-cell carcinoma and its clinical significance: a preliminary study

Objective To study the pattern of lymph node metastasis (LNM) in limited-stage primary esophageal small-cell carcinoma (PESC) and its guiding significance for clinical target volume delineation in radiotherapy.Methods A retrospective analysis was performed on the clinical data of 21 patients with limited-stage PESC who underwent esophagectomy in our hospital from January 2006 to July 2012 to analyze the rate and degree of LNM and distribution of metastatic lymph nodes.Results The mean number of dissected lymph nodes per patient was 27.9.There were 15 patients who had LNM ;8 patients had dispersed distribution of metastatic lymph nodes,and 7 patients had aggregated distribution of metastatic lymph nodes.The LNM rate was 71.4％,and the LNM degree was 17.2％.The Logistic univariate analysis showed that advanced T stage and long PESC lesion were the risk factors for LNM (P =0.004,P =0.044) and that advanced T stage and angiolymphatic invasion were the risk factors for dispersed distribution of metastatic lymph nodes (P =0.007,P =0.005).Conclusions The rate and degree of LNM are higher in PESC than in esophageal squamous cell carcinoma.Among the patients with limited-stage PESC,38％ have dispersed LNM.More research is recommended to evaluate the distribution of metastatic lymph nodes according to T stage and angiolymphatic invasion and investigate the value of prophylactic irradiation to the lymphatic drainage area of PESC. Key words: Esophageal neoplasms; Lymph node metastases; Clinical target volume; Radiotherapy

Surgical treatment and prognostic analysis of 109 patients with primary esophageal small cell carcinoma

Since the principles of treatment of primary esophageal small cell carcinoma (PESCC) remain still in controversy, the aim of this study was to investigate the clinical characteristics, treatment modalities and prognostic factors of this malignancy. The clinical data of 109 patients treated by surgery in our hospital between October 1989 and April 2009 were retrospectively reviewed and analyzed. According to the most recently published TNM staging system for esophageal cancer (AJCC 2009), there were 17 patients in stage Ib, 31 patients in stage II, 59 patients in stage III, and 2 patients in stage IV. All the data were analyzed using SPSS 15.0 software. The median survival time (MST) and overall survival rate (OS) were calculated and compared by the Kaplan-Meier method and log-rank test. The prognostic factors were calculated by Cox hazard regression model. Among all the 109 patients included, 93 patients were treated by radical esophagectomy, and 11 patients by palliative resection, while 5 patients by exploration. The median survival time (MST) of the whole group was 14.4 months and the 1-, 3- and 5-year overall survival rates (OS) were 56.9%, 17.6%, and 12.0%, respectively. The median survival time (MST) and 5-year overall survival rates (OS) were 18.5 months and 21.4% for pathological N0 cases, 23.5 months and 24.0% for N1 cases, 8.5 months and 0% for N2 cases, and 10.5 months and 0% for N3 cases, respectively (P < 0.001). The MST and 1-, 3- and 5-year OS of patients treated with postoperative chemotherapy were 17.0 months, 60.7%, 19.8%, and 13.0%, respectively, statistically significantly longer than the 7.0 months, 28.5%, 8.9% and 8.9%, respectively, of the patients without chemotherapy (P = 0.005). The pathological N stage and postoperative chemotherapy were independent prognostic factors by Cox multivariate analysis. Primary esophageal small cell carcinoma is an aggressive systemic disease, characterized by early and wide dissemination of lymph nodes and poor prognosis while treated with surgery or chemotherapy alone. Multimodality treatment based on radical esophagectomy should be recommended for patients in pathological stage I and II.

Primary esophageal small cell carcinoma

Primary esophageal small cell carcinoma ( PESC ) is a rare form of esophageal carcinoma which is with high degree of malignancy and early metastasis.Although the histological origin and etiology of PESC remains to largely unknown,one attractive viewpoint is that it derives from original pluripotent stem cells of esophageal mucosa.PESC have both epithelium and neuroendocrine cellular features.Neuroendocrine biomarkers including NES and Syn have been used for identification of PESC. Key words: Esophageal neoplasms ; Carcinoma, small cell; Tumor markers, biological

A Rare Cause of the Cough: Primary Small Cell Carcinoma of Esophagus—Case Report

Primary small cell carcinoma of the esophagus is a relatively rare malignancy. It is highly progressive and poorly prognostic in untreated conditions. In the western populations, the rate of primary small cell carcinoma in all esophageal cancer types is between 0.05% and 2.4%, while it is endemically increasing up to 7.6% in the eastern populations. Most of the cases are in extensive stage at the time of diagnosis. Surgery is the treatment of choice in limited stages, but treatment must be multimodal in primary small cell carcinoma of the esophagus. A 47-year-old woman was referred to our clinic with gradually increasing severe dry cough and slight difficulty in swallowing for 20 days. Chest X-ray graphy was normal, and computed tomography of the chest showed multiple mediastinal lymph nodes and hepatic metastases. Her endoscopic examination revealed an endoluminal vegetative mass between 20 cm and 23 cm of her esophagus. The case was reported as small cell carcinoma of the esophagus on histopathological examination. The case was assumed inoperable, and chemotherapy and radiotherapy were planned. We presented a rare cause of the cough and primary esophageal small cell carcinoma in this paper.

Clinical analysis of 42 cases with limited stage primary esophageal small cell carcinoma

Objective To investigate the clinical characteristics,diagnosis,treatment and prognosis of limited stage primary esophageal small cell carcinoma (PESC).Methods Clinical data was retrospectively analyzed for 42 patients with pathologically confirmed PESCs who underwent transthoracic esophagectomy with lymphadenectomy from Nov.1990 to Dec.2010 at the Cancer Hospital of Shantou University Medical College.The survival analysis was performed using Kaplan-Meier method.Results The clinical symptoms,imaging and endoscopic features of PESC were similar to those of esophageal squamous cell carcinoma (ESCC).Of the 26 cases that received pre-operative endoscopic biopsy,only five cases were diagnosed as PESC,while the other 21 cases were misdiagnosed as ESCC.The mean follow-up time of this series was 25.3 months (0-123 months).34 patients died of the disease during the follow-up; 7 were still alive and 1 was lost.The median survival time (MST) of the 41 patients was 13.0 months (95 ％ confidence interval 6.3-19.7),and the 6-,12-,24-,36-,and 60-month overall survival rates (OS) were 78.6 ％,57.5 ％,30.8 ％,23.7 ％,10.5 ％,respectively.Conclusion PESC is a rare disease with poor prognosis,and is prone to be misdiagnosed by endoscopic biopsy.Currently no standard treatment has been established. Key words: Esophageal neoplasms; Carcinoma, small cell; Treatment; Prognosis

Primary Esophageal Small Cell Carcinoma with Brain Metastasis and with CD56, KIT, and PDGFRA Expressions

Primary Esophageal Small Cell Carcinoma with Brain Metastasis and with CD56, KIT, and PDGFRA Expressions

Superficial primary small cell carcinoma of the esophagus: clinicopathological and immunohistochemical analysis of 15 cases

Primary esophageal small cell carcinoma (PESCC) is a relatively rare and aggressive tumor with poor prognosis. Systemic spreading and metastasis often occur at diagnosis. Although 5-year survival rate of superficial squamous cell carcinoma of the esophagus can be 86.1%, 5-year survival rate of superficial PESCC is still relatively low. This study mainly retrospectively analyzed clinicopathological and immunohistochemical features of 15 cases of superficial PESCC in our hospital from 1990 to 2004, in order to find suitable diagnostic markers and applicable therapies for this disease. The records mainly included presenting symptoms, demographics, diagnostic method, histopathology, follow-up, and therapy. Immunohistochemical staining of chromogranin A (CgA), neuron-specific enolase (NSE), synaptophysin (Syn), neuronal cell adhesion molecules (CD56), thyroid transcription factor-1 (TTF-1), cytokeration 34betaE12 (CK34betaE12), cytokeratin (AE1/AE3), and cytokeratin 10/13 was performed. Incidence of superficial PESCC accounted for 4.8% of that of superficial carcinoma of the esophagus during the same period. Initial symptoms of all patients were dysphagia or accompanied with retrosternal pain and upper abdominal pain, and duration of these symptoms was 75 days averagely. Mean age of patients was 58.8 years old, and the male-to-female ratio was 2.75 : 1. Lesions were mainly located at middle thoracic esophagus. One, 2, and 5-year survival rates were 66.7, 33.3, and 6.7%, respectively. The median survival time was 19 months and mean survival time was 23.7 months after diagnosis. The percentages of PESCC samples with positive immunoreactivity were NSE 100%, Syn 100%, AE1/AE3 100%, CD56 93.3%, TTF-1 60%, CgA 53.3%, CK34betaE12 6.7%, and cytokeratin 10/13 0%, respectively. Our study suggested that PESCC was a rare and aggressive tumor with high malignancy. Superficial PESCC had rapid progression and poor prognosis compared with superficial squamous cell carcinoma of the esophagus at the same stage. The systemic therapy based on combination of postoperative chemotherapy and radiotherapy might be an effective approach for the treatment of superficial PESCC as a systemic disease. Higher proportion of positive labeling of NSE, Syn, AE1/AE3, CD56, TTF-1, and CgA in PESCC was valuably applied in diagnosis and differential diagnosis.

Primary small cell carcinoma of esophagus: Report of 9 cases and review of literature

To analyze the clinical manifestations, pathological features and treatment of primary small cell carcinoma (SCC) of the esophagus and to review the literature on this entity. The records of 9 patients with primary esophageal small cell carcinoma were examined and the demographic data, presenting symptoms, methods of tumor diagnosis, and types of treatment given, response to treatment, pathologic findings, and clinical outcome were reviewed. Features of mixed patterns of histological differentiation and lymph node metastases were specifically sought. All the patients reported dysphagia, weight loss and chest pain as the initial symptoms. In 5 cases the tumors were located in the mid-esophagus, 3 cases in the lower third of the esophagus and 1 case in the upper third. The average length of esophageal involvement was 5 cm. They underwent radical resection, regional lymph node clearance and esophageal-stomach anastomosis in thorax or at neck. Two patients had a stage IIa disease, five had a stage IIb disease, and the other two had a stage III disease of International Union Contrele Cancer (UICC). All of them were histologically and immunohistochemically confirmed SCC of esophagus. Immunohistochemical staining for neuron-specific enolase (NSE), synaptophsin (Syn) and chromogranin A exhibited strong immunoreactivity in all specimens. Three of the nine resected specimens showed foci of squamous cell carcinoma in situ. Metastasis was present in 7 of 9 adjacent lymph nodes. All the patients survived the operations and made an uneventful postoperative recovery. They received adjuvant systemic chemotherapy and local radiation therapy after discharge. During follow-up, three patients developed multiple liver, brain, lung and bone metastases and died between 5 and 18 mo after the diagnosis. Three patients developed widespread metastasis disease and died between 18 and 37 mo after the diagnosis. There was no local tumor recurrence in these 6 patients. The other three patients were lost during follow-up. Primary small cell carcinoma of the esophagus is a rare but very malignant tumor. Radical resection combined with chemotherapy and radiotherapy is helpful in limited stage cases.

Primary esophageal small cell carcinoma with concomitant invasive squamous cell carcinoma or carcinoma in situ

Esophageal small cell carcinoma (SmCC) is a rarer, more highly aggressive, and more rapidly growing neoplasm than esophageal squamous cell carcinoma (SqCC). SmCC and SqCC also differ in terms of chemotherapy of choice, response to therapy, and prognosis. Accordingly, it is important to differentiate the 2 carcinomas. We studied the histology and immunohistochemical profiles of 6 cases of esophageal SmCC to elucidate the correct diagnosis of this tumor. We performed immunohistochemical analysis antibodies against cytokeratins (CKAE1/AE3, CKCAM5.2, CK34βE12, CK7, CK8, CK10/13, and CK19), epithelial membrane antigen (EMA), neural cell adhesion molecule (NCAM; CD56), neuron-specific enolase (NSE), chromogranin-A, S-100 protein, carcinoembryonic antigen (CEA), E-cadherin, thyroid transcription factor-1 (TTF-1), and p53. In 3 of the 6 SmCCs, heterogeneous components of in situ or invasive SqCC were observed. SqCC was found in the mucosa adjacent to the main SmCC, and the boundary between SmCC and SqCC was distinct, with no transitional features. Staining for NCAM, NSE, and chromogranin-A was positive in SmCCs, but negative in SqCCs. Both SmCCs and SqCCs were positive for CKAE1/AE3, CKCAM5.2, CK8, and EMA, but only SqCCs were positive for CK34βE12 and CK19. Moreover, SmCCs containing SqCC components were positive for CEA and E-cadherin, whereas SmCCs without SqCC were negative. Our study suggests that NCAM and NSE are useful markers in diagnosing esophageal SmCC, and CK34βE12 and CK19 are useful for differentiating SqCC components from SmCC.