Advanced Small-Cell Colon Carcinoma
According to the 2010 WHO classification of neuroendocrine neoplasia (NET), NET was categorized into grade 1 and grade 2 based on the malignant potential of metastasis, and tumors with high malignancy were divided into NEC or mixed adenoendocrine carcinoma, which includes an element of adenocarcinoma of more than 30%. The present case was pathologically diagnosed as a small-cell carcinoma mixed with poor to moderate adenocarcinoma elements of less than 30%, and was categorized as NEC based on WHO classifications. When applying the present WHO classification, special attention should be paid because previously well or poorly differentiated endocrine carcinomas are redefined separately as NET grade 2 and NEC.
A definitive diagnosis was made histopathologically, and immunohistochemical staining greatly helps in diagnosis. Saclarides et al. reported that more than a few cases initially diagnosed as carcinoid were changed to NEC after histopathological analysis. In the present case, diagnosis was made preoperatively based on the immunohistochemical staining of chromogranin A, synaptophysin, and CD56. An endoscopic biopsy diagnosis is occasionally changed from well to moderately differentiated colon adenocarcinoma to NEC by pathological evaluations after surgery. When any specific structures of NEC are histologically found, routine immunohistochemical staining contributes to appropriate diagnosis and continuous early treatment.
Chemotherapy for NEC is often performed based on the regimen for small-cell lung carcinoma. The latest guidelines for small-cell lung carcinoma from the National Comprehensive Cancer Network (NCCN) recommend etoposide plus platinum agents such as cisplatin or carboplatin for limited stage, and adding irinotecan instead of etoposide for extensive stage. The present case initially received cisplatin plus irinotecan therapy, and secondly carboplatin plus etoposide therapy was selected because the tumor acquired resistance to cisplatin plus irinotecan therapy. In the present case, which was considered to have a high recurrence risk, UFT and UZEL were selected for maintenance and carboplatin plus etoposide therapy after the first cisplatin plus irinotecan therapy was administered based on a colon cancer regimen. Although the disease-free interval from the first cisplatin plus irinotecan therapy to recurrence was approximately four months, cisplatin plus irinotecan therapy was selected again. In the NCCN guidelines for small-cell lung cancer, when a recurrence is observed less than six months after finishing chemotherapy, a different treatment regimen is recommended. It might have been better to change from cisplatin plus irinotecan therapy to carboplatin plus etoposide therapy at the time of recurrence because the tumor had already shown resistance to cisplatin plus irinotecan therapy.
It is very rare for patients with small-cell colon carcinoma to survive for approximately 30 months after being diagnosed with stage IV disease and peritoneal disseminations. Some reports have shown long-term survival despite an advanced stage by combination of operation and effective chemotherapy. Unfortunately, patient characteristics associated with positive results from chemotherapy and favorable outcomes are still unknown because so few cases achieve long-term survival. A recent clinical trial showed the efficacy of amrubicin, an anthracycline agent with potent topoisomerase II inhibition activity, in improving survival time as second-line treatment for patients with small-cell lung cancer. Although the number of cases was limited, Asayama et al. also reported the efficacy of amrubicin as first-line treatment for five cases of gastrointestinal endocrine carcinoma. Earlier reports suggested that a certain percentage of patients with small-cell colon carcinoma had sensitivity for chemotherapy and achieved a better prognosis.
In general, small-cell colon carcinoma has a high risk for recurrence and the follow-up method is important. Because recurrence sites are found in various organs, such as lymph nodes, liver, lung, and brain, less invasive whole body screening is needed. A recent study showed the effectiveness of somatostatin receptor scintigraphy on diagnosis and follow up by using an indium pentetreotide that specifically associated with the somatostatin receptor in NEC. However, the superiority of CT, magnetic resonance imaging, and somatostatin receptor scintigraphy is still controversial, and regular whole body screening and reassessment of chemotherapeutic effect is essential.
Discussion
According to the 2010 WHO classification of neuroendocrine neoplasia (NET), NET was categorized into grade 1 and grade 2 based on the malignant potential of metastasis, and tumors with high malignancy were divided into NEC or mixed adenoendocrine carcinoma, which includes an element of adenocarcinoma of more than 30%. The present case was pathologically diagnosed as a small-cell carcinoma mixed with poor to moderate adenocarcinoma elements of less than 30%, and was categorized as NEC based on WHO classifications. When applying the present WHO classification, special attention should be paid because previously well or poorly differentiated endocrine carcinomas are redefined separately as NET grade 2 and NEC.
A definitive diagnosis was made histopathologically, and immunohistochemical staining greatly helps in diagnosis. Saclarides et al. reported that more than a few cases initially diagnosed as carcinoid were changed to NEC after histopathological analysis. In the present case, diagnosis was made preoperatively based on the immunohistochemical staining of chromogranin A, synaptophysin, and CD56. An endoscopic biopsy diagnosis is occasionally changed from well to moderately differentiated colon adenocarcinoma to NEC by pathological evaluations after surgery. When any specific structures of NEC are histologically found, routine immunohistochemical staining contributes to appropriate diagnosis and continuous early treatment.
Chemotherapy for NEC is often performed based on the regimen for small-cell lung carcinoma. The latest guidelines for small-cell lung carcinoma from the National Comprehensive Cancer Network (NCCN) recommend etoposide plus platinum agents such as cisplatin or carboplatin for limited stage, and adding irinotecan instead of etoposide for extensive stage. The present case initially received cisplatin plus irinotecan therapy, and secondly carboplatin plus etoposide therapy was selected because the tumor acquired resistance to cisplatin plus irinotecan therapy. In the present case, which was considered to have a high recurrence risk, UFT and UZEL were selected for maintenance and carboplatin plus etoposide therapy after the first cisplatin plus irinotecan therapy was administered based on a colon cancer regimen. Although the disease-free interval from the first cisplatin plus irinotecan therapy to recurrence was approximately four months, cisplatin plus irinotecan therapy was selected again. In the NCCN guidelines for small-cell lung cancer, when a recurrence is observed less than six months after finishing chemotherapy, a different treatment regimen is recommended. It might have been better to change from cisplatin plus irinotecan therapy to carboplatin plus etoposide therapy at the time of recurrence because the tumor had already shown resistance to cisplatin plus irinotecan therapy.
It is very rare for patients with small-cell colon carcinoma to survive for approximately 30 months after being diagnosed with stage IV disease and peritoneal disseminations. Some reports have shown long-term survival despite an advanced stage by combination of operation and effective chemotherapy. Unfortunately, patient characteristics associated with positive results from chemotherapy and favorable outcomes are still unknown because so few cases achieve long-term survival. A recent clinical trial showed the efficacy of amrubicin, an anthracycline agent with potent topoisomerase II inhibition activity, in improving survival time as second-line treatment for patients with small-cell lung cancer. Although the number of cases was limited, Asayama et al. also reported the efficacy of amrubicin as first-line treatment for five cases of gastrointestinal endocrine carcinoma. Earlier reports suggested that a certain percentage of patients with small-cell colon carcinoma had sensitivity for chemotherapy and achieved a better prognosis.
In general, small-cell colon carcinoma has a high risk for recurrence and the follow-up method is important. Because recurrence sites are found in various organs, such as lymph nodes, liver, lung, and brain, less invasive whole body screening is needed. A recent study showed the effectiveness of somatostatin receptor scintigraphy on diagnosis and follow up by using an indium pentetreotide that specifically associated with the somatostatin receptor in NEC. However, the superiority of CT, magnetic resonance imaging, and somatostatin receptor scintigraphy is still controversial, and regular whole body screening and reassessment of chemotherapeutic effect is essential.
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