Primary High-grade Neuroendocrine Carcinoma of the Esophagus

Abstract

Primary high-grade neuroendocrine carcinoma of the esophagus (HNCE) is rare and poorly understood. In this study, we aimed at delineating the clinicopathologic and immunohistochemical characteristics of HNCE diagnosed on the basis of the World Health Organization criteria for pulmonary neuroendocrine carcinomas. We identified 42 (3.8%) consecutive resection cases of HNCE among 1105 esophageal cancers over a 7-year period. Patients' mean age was 62 years (range, 47 to 79 y) with a male to female ratio of 3.7. Dysphagia was present in 79% of patients and tobacco abuse in 50%. Most tumors were centered in the middle (52%) or lower (36%) esophagus; 48% were ulcerated and 31% exophytic. All tumors were sharply demarcated with a pushing border in either solid sheet (83%) or nodular (17%) growth patterns. Pure HNCE was found in 57%, and the remainder also exhibited small components of squamous cell carcinoma (SqCC) or glandular, signet ring cell differentiations. SqCC in situ was present in 50%. Most tumors (88%) were the small cell type with pure oat-like cells in 52%, and the larger spindled, anaplastic, and giant cells were common. Tumor crush artifact (98%) and the Azzopardi effect (88%) were widespread. Extensive lymphovascular (50%) and perineural (33%) invasion and metastasis to regional (48%) and abdominal celiac lymph nodes (29%) were observed. Neoplastic cells were immunoreactive to synaptophysin (100%), CD56 (93%), chromogranin A (67%), p63 (55%), TTF-1 (71%), CK8/18 (90%), CD117 (86%), HER2 (16%), and p16 (84%) antibodies. The 5-year survival rate was 25%, similar to that of SqCC. Lymphovascular and perineural invasion was associated with a worse prognosis.

The clinical features and treatment modality of esophageal neuroendocrine tumors: a multicenter study in Korea

“…This is because neuroendocrine cells are mainly distributed in mucosal glands of the distal esophagus [6, 12, 13]. In 1990, Attar et al noted a predominant distribution of neuroendocrine carcinomas in the lower third of the esophagus, similar to our results, and related this to the abundance of endocrine cells in this region [12, 13].…”

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

“…The tumor samples were regarded as positive when more than 10% of nuclei were stained for p53 as previously reported [12]. The positivity of c-kit was evaluated by the immunoreactivity of cytoplasm in the tumor cells as previously reported [1]. Each immunostaining was reviewed and independently scored by two pathologists independently (K. T. and R. K.).…”

“…Neuroendocrine carcinoma (NEC) is a relatively rare disease with a reported incidence between 0.4% and 2% among all malignancies of the esophagus [1–3]. NEC is categorized into two morphological types: small cell type and large cell type.…”

“…Microscopically, the features of neuroendocrine cells are formation of nested and trabecular growth with peripheral palisading and rosette formation in the tumors. High frequency of venous invasion, lymphatic invasion and perineural invasion are also seen [1]. …”

“…However, even for LD, multi-modality treatments such as surgery followed by adjuvant chemo-(radio)-therapy or neo-adjuvant chemotherapy followed by surgery are commonly recommended [6]. Although the role of surgery is controversial, the co-existence of squamous cell carcinoma with NEC makes it difficult for complete response by chemotherapy which is effective for NEC but not for squamous cell carcinoma [1]. From this point of view, multimodal treatment including surgical resection could be considered.…”