| Abstract|| |
Occurrence of carcinoid tumors in the esophagus is exceedingly rare. We present a case of an atypical carcinoid in the mid esophagus in a 56-year-old male, presenting with dysphagia. Esophagectomy was performed followed by postoperative chemotherapy. Histopathological and immunohistochemical studies were carried out. The patient succumbed to liver and lung metastasis, 6 months after the initial diagnosis, highlighting the poor prognosis of the condition.
Keywords: Atypical carcinoid, esophagus, immunohistochemistry, poor prognosis, rare
|How to cite this article:|
Shah MJ, Birwa SB, Samanta ST, Patel MA. Atypical carcinoid of the esophagus. Indian J Pathol Microbiol 2015;58:223-5
| Introduction|| |
Most common histological type of esophageal tumor is Squamous cell carcinoma (SCC), followed by Adenocarcinoma. Neuroendocrine tumors (NET) of the esophagus are very rare It was first reported in 1974 that esophageal carcinoids arise from the argyrophil endocrine cells, which are amine precursor uptake and decarboxylation cells of the mucosa.  In 2010, the WHO proposed a new diagnostic criteria for the disease on the basis of mitotic count and Ki67 index and graded these tumors as G1 (NET) <2 mitoses/10 hpf and/or ≤2% Ki67 index, G2 (NET/atypical carcinoid) 2-20 mitoses/10 hpf and/or 3-20% ki67 index, G3 neuroendocrine carcinomas (NEC) >20 mitoses/10 hpf and/or >20% Ki67 index. Most esophageal neuroendocrine neoplasms are NECs (G3).  Here we report a rare case of an atypical carcinoid (NET G2) in the mid esophagus, of which very few cases have been reported so far.
| Case Report|| |
A 56-year-old man, presented with a 1-month history of progressive dysphagia and weight loss. No clinical features of carcinoid syndrome were present.
Computed tomography (CT) scan of the thorax revealed soft tissue density along the lateral wall of mid-lower esophagus causing narrowing of the lumen. Biopsy was performed and reported as malignant epithelial tumor. Immunohistochemistry (IHC) was not done.
The patient underwent transhiatal esophagectomy. The specimen measured 13.8 cm × 2.7 cm × 2.5 cm (esophagus) and 8.1 cm × 3.5 cm × 2.4 cm (stomach). A growth was identified in mid-esophagus measuring 3.9 cm in length, involving half circumference and half thickness of the esophageal wall [Figure 1]. Section from the mass showed pleomorphic polygonal cells in nests and cords with vascular stroma, focal necrosis and mitotic rate of 5-6/10 hpf [Figure 2]a and b. Diagnosis of atypical carcinoid/NET, G2 was made. The tumor infiltrated the inner muscle layer of the esophageal wall. Lymphovascular invasion was not seen. Margins were free from tumor. Sections from nodes showed tumor metastasis in one lymphnode at gastro-esophageal junction (1/4). Hence, our patient was in stage IIB (T 2 N 1 M 0 ). On IHC, the tumor expressed chromogranin and synaptophysin [Figure 3]a. P63 was negative. MIB1 (Ki67) expression was 10-12% [Figure 3]b. Postoperatively, patient was given chemotherapy with carboplatin and etoposide, of which he completed 6 cycles. 2 months after the operation, the patient again presented with dysphagia and underwent endoscopic stricture dilatation. 5 months postoperative, postchemotherapy, thorax CT scan revealed wall thickening at anastomotic site, liver metastasis [Figure 4]a lung metastasis [Figure 4]b, nodal mass in posterior mediastinum, few nodes in superior mediastinal and para-aortic region and loculated fluid collection along right lateral chest wall. 6 months postoperative and post chemotherapy, the patient expired.
|Figure 1: Transhiatal esophagectomy showing atypical carcinoid in the mid esophagus|
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|Figure 2: (a) Atypical carcinoid of esophagus showing typical morphology (H and E, ×10). (b) (H and E, ×40)|
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|Figure 4: Computed tomography scan showing (a) liver metastasis (b) lung metastasis|
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| Discussion|| |
Carcinoid tumors have been reported throughout the gastrointestinal tract, commonly in the appendix, small bowel and rectum. However, carcinoid tumors of the esophagus are exceedingly rare. Carcinoid tumors are NETs thought to arise from amine precursor uptake and decarboxylation cells. 
They usually occur in older men. In most of the reported cases, the patients had dysphagia and only one had carcinoid syndrome. 
Therefore, it is difficult to differentiate esophageal carcinoid tumors clinically from adenocarcinoma and SCC.  Our case was also an elderly man presenting with dysphagia and weightloss.
Review of literature by Lindberg et al. reported ten of the fourteen carcinoid tumors in the lower thoracic esophagus, two lesions occurred in the mid thoracic esophagus and two were in the upper esophagus. The tumors ranged in size from 1.0 to 12.0 cm with an average of 4.0 cm.  Our case had mid esophageal tumor measuring 3.9 cm in length.
Earlier histological appearance of an atypical carcinoid was established according to the criteria proposed by Arrigoni et al. for bronchial carcinoids,  based on:
- Increased mitotic activity.
- Pleomorphism, nuclear irregularity, hyperchromatism, abnormal nuclear:cytoplasmic ratio.
- Hypercellularity with disorganization of architecture.
- Areas of tumor necrosis.
In our case, atypical carcinoid diagnosis was made on the basis of mitotic count, MIB1 (Ki67) expression and necrosis.
In the agreement with Lindberg et al.,  we can state that distinguishing atypical carcinoid from poorly differentiated carcinoma may be difficult sometimes due to their similarity in cellular morphology.
Xiaogang et al. mentions chromogranin and NSE as good markers for tumors with neuroendocrine features, but are not useful for accurately identifying NET subtypes.  In our case too, chromogranin A and synaptophysin expression helped to establish the neuroendocrine nature of the tumor.
Casas et al. described that clinical staging, tumor size and administration of chemotherapy influence patient outcomes. 
In contrast to other gastrointestinal sites, there is no proposal for tumor node metastasis (TNM)/staging classification for neuroendocrine neoplasms of the esophagus. Hence, these tumors may be staged according to the TNM/staging classification for esophageal carcinomas. , In our case, the patient was T 2 N 1 M 0 (stage II b) on presentation.
Due to small number of cases reported so far, optimum management of atypical carcinoid of esophagus is unclear.
Xiaogang et al. suggests first radical esophagectomy with mediastinal lymphnode dissection done for staging, followed by a combination of radiotherapy and chemotherapy. In their case, in spite of receiving adjuvant radiotherapy and chemotherapy, patient died of liver metastasis at 11 months. 
In another case reported by Oz et al., the patient died of recurrence of gastroesophageal atypical carcinoid at 20 months. 
Our patient received chemotherapy post op and died at 6 months from lung and liver metastasis.
In agreement with Xiaogang et al.,  we believe that atypical carcinoid of the esophagus has an unfavorable prognosis and may present with local recurrence and distant metastasis.
To summarize, most neuroendocrine neoplasms of esophagus are NEC located in lower third of the esophagus and are NEC grade 3 tumor, while, in our case, it was NET G2 of the middle third.
This tumor, even though it was NET G2, behaved aggressively like NEC G3.
This may suggest that esophageal NET G2 may be a biologically aggressive tumor.
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Dr. Shah B Birwa
Room No. 412, The Gujarat Cancer and Research Institute, Civil Hospital Campus, Asarwa, Ahmedabad - 380 016, Gujarat
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3], [Figure 4]