Small cell carcinomas in gastrointestinal tract: Immunohistochemical and clinicopathological features

School of Medicine, National Yang-Ming University, Taipei, Taiwan.
Journal of clinical pathology (Impact Factor: 2.92). 07/2010; 63(7):620-5. DOI: 10.1136/jcp.2010.077024
Source: PubMed


To test the incidence of the expression of the immunohistochemical markers that aid diagnosis of gastrointestinal tract small cell carcinoma (GI-SmCC) and to evaluate the incidence of mixed endocrine-exocrine carcinomas in GI-SmCC.
Immunohistochemical studies of three antibodies against epithelial markers (CK8, AE1/AE3, EMA), four neuroendocrine differentiation markers (synaptophysin (Syn), neuron specific enolase (NSE), neuronal cell adhesion molecules (CD56), chromogranin A (CgA)), and a transcription factor (thyroid transcription factor 1 (TTF-1)) were performed. The incidence of non-endocrine carcinoma component was evaluated in 42 GI-SmCCs (11 in the oesophagus, 15 in the stomach, 15 in the colon, and 1 in the small intestine).
The percentages of GI-SmCC with positive immunoreactivity were: CK8 92.9%, AE1/AE3 76.2%, EMA 71.4%, Syn 100%, NSE 100%, CD56 90.5%, CgA 61.9%, TTF-1 21.4%. The low molecular weight cytokeratin CK8 is more commonly expressed in GI-SmCC than is the expression of AE1/AE3 or EMA. Synaptophysin and NSE are expressed in all GI-SmCCs studied. Non-endocrine carcinoma components were demonstrated in 8 patients (4 in the oesophagus and 4 in the stomach).
In detecting GI-SmCC, epithelial marker CK8 is more sensitive than AE1/AE3 or EMA, and neuroendocrine differentiation markers synaptophysin and NSE are the most useful markers. TTF-1 positivity is not uncommon in GI-SmCC, but cases with negative TTF-1 staining may indicate an extra-pulmonary primary. Non-endocrine carcinoma components were demonstrated in about 30% of oesophagus and stomach SmCC; the neoplasms should be diagnosed as mixed endocrine-exocrine carcinoma.

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    • "Immunohistochemistry has not proven useful in distinguishing primary peri-ampullary SCC from metastatic SCLC.15 Although a high percentage of lung primaries express thyroid transcription factor 1 (TTF-1), this marker has shown variable positivity in patients with extra-pulmonary small cell carcinoma.16–19 Furthermore, the expression of TTF-1 has not been well explored in pancreatic SCC, with only one reported negative case in the literature to date.20 Recent studies have demonstrated that serum pro-gastrin releasing peptide (ProGRP) and serum neuron specific enolase (NSE) levels can be elevated in patients with pancreatic SCC, similar to the clinical experience with lung primaries.21,22 "
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    ABSTRACT: Primary pancreatic small cell carcinoma (SCC) is rare, with just over 30 cases reported in the literature. Only 7 of these patients underwent surgical resection with a median survival of 6 months. Prognosis of SCC is therefore considered to be poor, and the role of adjuvant therapy is uncertain. Here we report two institutions' experience with resectable pancreatic SCC. Six patients with pancreatic SCC treated at the Johns Hopkins Hospital (4 patients) and the Mayo Clinic (2 patients) were identified from prospectively collected pancreatic cancer databases and re-reviewed by pathology. All six patients underwent a pancreaticoduodenectomy. Clinicopathologic data were analyzed, and the literature on pancreatic SCC was reviewed. Median age at diagnosis was 50 years (range 27–60). All six tumors arose in the head of the pancreas. Median tumor size was 3 cm, and all cases had positive lymph nodes except for one patient who only had five nodes sampled. There were no perioperative deaths and three patients had at least one postoperative complication. All six patients received adjuvant therapy, five of whom were given combined modality treatment with radiation, cisplatin, and etoposide. Median survival was 20 months with a range of 9–173 months. The patient who lived for 9 months received chemotherapy only, while the patient who lived for 173 months was given chemoradiation with cisplatin and etoposide and represents the longest reported survival time from pancreatic SCC to date. Pancreatic SCC is an extremely rare form of cancer with a poor prognosis. Patients in this surgical series showed favorable survival rates when compared to prior reports of both resected and unresectable SCC. Cisplatin and etoposide appears to be the preferred chemotherapy regimen, although its efficacy remains uncertain, as does the role of combined modality treatment with radiation.
    Rare tumors 01/2011; 3(1-3). DOI:10.4081/rt.2011.e5

  • New England Journal of Medicine 01/2011; 364(4):362-70. DOI:10.1056/NEJMcpc1000965 · 55.87 Impact Factor
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    ABSTRACT: Thyroid transcription factor 1 (TTF-1) plays a key role in morphogenesis of the lungs and is expressed in up to 90% of pulmonary small cell carcinomas. This explains why this marker is frequently used in the search for the primary origin of metastatic endocrine tumours. Here we report on a TTF-1 expressing mixed endocrine-exocrine carcinoma of the common bile duct in a patient with pulmonary nodules that did not appear to be neoplastic. TTF-1 positivity in pulmonary and extrapulmonary neuroendocrine tumours is reviewed, and we conclude that TTF-1 expression in neuroendocrine tumours of the small-cell type are not uncommon at extrapulmonary locations. Therefore, immunohistochemistry for TTF-1 in such tumours should be interpreted with caution.
    10/2011; 3(10):144-7. DOI:10.4251/wjgo.v3.i10.144
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