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Highlights • Cervical lymph node SmCC as a primary tumor’s location, was never described in the literature according to what we know. • AC neuroendocrine carcinoma of the tonsil has never been described in the literature up to our knowledge. • A review of the literature was performed, indicating treatment and disease’s prognosis. • In 2012, the 2005 WHO classification of neuroendocrine tumors of the head and neck region was modified by adding the ranges of the Ki-67 and suggested that LCNEC should be considered a distinct disease entity and be separated from AC., Introduction Primary neuroendocrine carcinomas are uncommon head and neck malignancies. Their classification is still debated. We report four cases of unusual primary locations of neuroendocrine carcinomas of head and neck region emphasizing two entities and rare sites that were never described in the literature to the best of our knowledge. Presentation of cases We reported four different cases of neuroendocrine carcinomas (nasal cavity, larynx, lymph nodes and tonsil) treated in our institution. The diagnosis was made by biopsy and confirmed by Immunohistochemical study. We underscored 2 atypical and rare entities in their location and anatomo histopathological type. Chemotherapy and radiotherapy were proposed for patients with nasal’s and laryngeal locations. This latter had also undergone surgery. For lymph node location, the patient received decompressive radiotherapy alone. The patient diagnosed with neuroendocrine carcinoma of the tonsil didn’t get any treatment except initial tonsillectomy for diagnosis purposes. Regarding the evolution in our case series, 2 patients had a relapse with local and regional metastasis. Among the 4 patients, 50 % passed away, one is still alive with deterioration of his general status and one is lost to follow-up and refused undergoing further investigations. Discussion There is confusion in the literature regarding the classification of neuroendocrine carcinomas. According to the 2005 WHO, these lesions, can be subdivided into TC, AC (including LCNEC), SmCC, combined SmCC with nonsmall cell carcinoma, and paraganglioma. Their treatment is still debated. Through an overview of the literature, we have gathered the main studies and 2 meta-analysis summarizing the mainstay treatment and disease’s outcome. Conclusion Neuroendocrine carcinomas of head and neck region are aggressive tumors with poor prognosis, low incidence and their diagnosis is not obvious. The treatment protocol depends on the type, the site of the lesions, and metastasis status. It’s still not well codified.

Various types of circulating tumor cell (CTC) detection systems have recently been developed that show a high CTC detection rate. However, it is a big challenge to find a system that can provide better prognostic value than CellSearch in head-to-head comparison. We have developed a novel semi-automated CTC enumeration system (fluidic cell microarray chip system, FCMC) that captures CTC independently of tumor-specific markers or physical properties. Here, we compared the CTC detection sensitivity and the prognostic value of FCMC with CellSearch in breast cancer patients. FCMC was validated in preclinical studies using spike-in samples and in blood samples from 20 healthy donors and 22 breast cancer patients in this study. Using spike-in samples, a statistically higher detection rate (p = 0.010) of MDA-MB-231 cells and an equivalent detection rate (p = 0.497) of MCF-7 cells were obtained with FCMC in comparison with CellSearch. The number of CTC detected in samples from patients that was above a threshold value as determined from healthy donors was evaluated. The CTC number detected using FCMC was significantly higher than that using CellSearch (p = 0.00037). CTC numbers obtained using either FCMC or CellSearch had prognostic value, as assessed by progression free survival. The hazard ratio between CTC + and CTC − was 4.229 in CellSearch (95% CI, 1.31 to 13.66; p = 0.01591); in contrast, it was 11.31 in FCMC (95% CI, 2.245 to 57.0; p = 0.000244). CTC detected using FCMC, like the CTC detected using CellSearch, have the potential to be a strong prognostic factor for cancer patients.