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    Colorectal neuroendocrine carcinoma:A case report and review of the literature

    2019-08-14 07:42:54TomoakiYoshidaKenyaKamimuraKazunoriHosakaKojiDoumoriHiromitsuOkaAkitoSatoYasuoFukuharaShojiWatanabeTomomiSatoAkiraYoshikawaTakashiTomidokoroShujiTerai
    World Journal of Clinical Cases 2019年14期

    Tomoaki Yoshida,Kenya Kamimura,Kazunori Hosaka,Koji Doumori,Hiromitsu Oka,Akito Sato,Yasuo Fukuhara,Shoji Watanabe,Tomomi Sato,Akira Yoshikawa,Takashi Tomidokoro,Shuji Terai

    Abstract

    Key words: Neuroendocrine carcinoma;Colon;Colorectal mixed adenoneuroendocrine carcinoma;Growth;Case report

    INTRODUCTION

    Neuroendocrine carcinoma (NEC) of colon and rectum is a rare neuroendocrine tumor (NET) type that accounts for < 1% of all colorectal malignancies[1].The clinical progression of NECs includes highly aggressive growth and rapid dissemination along with a high tendency for metastasis[2].Moreover,these tumors could be detected at advanced stage[3].The 3-year overall survival (OS) was estimated to be 5%-27%[1,4,5],and response to chemotherapy was reported as the only predictive factor in patients with metastasis[1].Because of its aggressive nature and high recurrence rate of the NEC,adjuvant chemotherapy constitutes a critical part of the treatment and significantly improves survival[4].Although platinum-based regimens are widely used as first-line chemotherapy for the treatment of patients with advanced NEC,no standard regimen has yet been established.A previous study has reported that some cases who received chemotherapy showed the complete response (CR) or partial response (PR) to the advanced NEC;however,more than half of patients showed progressive response[6].

    Additionally,some NEC cases showed aggressive progression and outward growth with the invasion of surrounding tissues.These aggressive tumors lead to serious health issues such as colonic obstruction and internal organ exclusion.The management of such health issues is sometimes challenging;moreover,an appropriate therapeutic strategy has not yet been proposed because of rareness of the aggressive NEC.

    Here,we attempted to present a patient with NEC that showed aggressive tumor progression.Although the patient received various therapeutic options,such as chemotherapy or intestinal self-expandable metallic stent,all those treatments have been unsuccessful yet.

    CASE PRESENTATION

    Chief complaints

    A 55-year-old man was admitted to our hospital with a huge abdominal mass.He complained of palpable abdominal mass,while painless mass two months prior to the presentation.

    History of past illness

    He had no significant history of past illness.

    Physical examination

    Physical examination showed a palpable tumor and a relatively soft mass associating with poor movability in the right upper quadrant.

    Laboratory examinations

    Laboratory findings showed an elevated white blood cell count (9740 /μL),platelet count (37.3 × 104/μL),C-reactive protein (4.99 mg/dL),lactate dehydrogenase (328 IU/L),and hemoglobin level (9.4 g/dL).Carcinoembryonic antigen showed mild elevation of 9.5 ng/mL,while other tumor markers were in normal range (Table 1).

    Further progress,diagnosis,treatment and outcome

    Abdominal contrast-enhanced computed tomography (CT) showed an irregularly shaped,10 cm,as well as an enhanced mass in the transverse colon at the hepatic flexure (Figure 1A) and suspicious of metastatic tumors in the liver (Figure 1B).Colonoscopy showed the mass in the right transverse colon with significant stenosis(Figure 1C) due to submucosal elevation of the tumor (Figure 1D),while the lumen had a necrotic tissue (Figure 1E) evidenced by colonic enema with water-soluble contrast medium showing an irregular shape in the lumen of colon (Figure 1B).Following the mucosal biopsy for the histological analysis,a self-expandable metallic stent was successfully placed.However,the patient re-admitted to our hospital because of the sudden onset and severe abdominal pain at 5 days after the placement.The contrast-enhanced CT of the abdomen showed intraperitoneal free-air associated with the colon tumor (Figure 1F).The hematoxylin and eosin (HE) staining showed that the tumor cells were poorly differentiated (Figure 2A) with hemorrhage in the tumor (Figure 2B) and significantly stained positively for Synaptophysin (Figure 2C).In addition,Ki67 staining showed a highly proliferative pattern with the Ki67 index of 90% (Figure 2D).

    FINAL DIAGNOSIS

    Based on these findings,the tumor was diagnosed with NEC,and the tumor showed perforation to the outside the colon probably due to the expandable growth of the tumor.

    TREATMENT

    The tumor showed severe invasion to the surrounding tissues;therefore,it was considered to be curatively unresectable,and anastomosis between the ileum and left colon was surgically developed that followed by chemotherapy.

    OUTCOME AND FOLLOW-UP

    Although the patient was treated with multiple chemotherapies,such as irinotecan +cisplatin (as the first-line therapy) and etoposide + carboplatin (as the second-line therapy);however,the tumor showed no significant response,and disease was rapidly progressed due to this invasive growth,in which the tumor induced the bile duct and duodenal obstruction by tumor progression.An additional stent for the duodenal stenosis was also placed;however,the appetite and general condition did not recover and he died 4 mo after the diagnosis.

    DISCUSSION

    The World Health Organization classification,published in 2010,divides NETs of the digestive tracts into NET grade (G) 1,NET G2,and NECs,based on mitotic counts and the Ki-67 proliferation index,regardless of tumor size,extent,or location,and also the colorectal NEC is a rare tumor with the incidence rate of 0.1%[1].In addition,NEC and colorectal mixed adenoneuroendocrine carcinoma (MANEC) revealed highgrade cancer cells evidenced by high level of Ki-67 index (> 20%).The advanced NEC typically associates with the expansive growth pattern similar to that associates with the stage II colon cancer,i.e.,yellowish ulcer and raised margin of non-neoplastic mucosa like submucosal tumor[5].Colorectal NEC involves high malignant potential with poor differentiation and high invasiveness,while its prognosis is worse than colorectal adenocarcinoma.The median survival rate and relative survival (%) at 5 years of NEC and adenocarcinoma were 7.1-14.7 and 36.0 mo,and 8.0%-16.3% and50.2%,respectively.In addition,MANEC showed significantly poor OS compared with adenocarcinoma[3].Because of the aggressive progression,NEC was mainly detected at advanced stage in comparison with adenocarcinoma resulted in the fact that 57.9%-67.5% of NEC patients were initially diagnosed with the stage IV compared with the finding that 25.2% of cases with adenocarcinoma were diagnosed with stage IV[1,3,6].These findings suggest that neuroendocrine differentiation is the cause of higher malignant potential and worse prognosis.Table 2 presents the characteristics of 59 cases with advances NEC and MANEC,while the terms “colon”and “neuroendocrine carcinoma” were searched in PubMed,and the available clinical information was summarized.

    Table1 Results of laboratory investigation on the day of admission

    Although a reliable treatment guideline has not presented yet,chemo-therapy plays a key role in treat-ment of patients with advanced NEC.Platinum-based chemotherapy,as a therapeutic strategy,is often used and the response rate is 42% to NEC that is relatively lower than that of 67% for small cell lung cancer[6].A previous study proposed the effectiveness of 5-fluorouracil (5-FU)-based chemotherapy[7];however,as mentioned earlier,a standard regimen for NEC has not been developed yet.It has also been reported that a regimen for the MANEC,comprising neoplasms with both neuroendocrine carcinomatous and adenocarcinomatous components,depends on which component dominantly contributes.In the present research,the number of patients with NEC and MANEC was 44 and 13,and the mean age was 61.5 and 56.2 years old,respectively (other two patients were diagnosed as the combination of NEC with squamous cell carcinoma).Besides,29 patients were died due to these tumors,while 15 patients were saved by treatment with tumor resection and chemotherapy.The OS of 48 patients who received the tumor resection was 19.2 mo,which was significantly higher than 3.4 mo belonged to 7 patients who did not undergo surgical resection.These results highly reveal that surgical resection is essential to prolong prognosis.However,a poor prognosis was observed in the majority of those patients because of the delayed diagnosis similar to our case,and we therefore were unable to perform the surgical treatment.To follow the chemotherapy,an effective stenting for the obstructive tumor is vital for treatment and also for quality of life (QOL) of the patients as significant rapid tumor progression in both inside and outside the colon are clinical features of NEC and may cause intestinal tract obstruction and also stenosis of the surrounding organs,including small intestine.The rapid growth resulted in the huge tumor upon the diagnoses,as our findings showed that the average diameter of NEC was 76.8 mm,and growth toward outside of the colon,outward invasion,which was observed in 42% of the patients,and similar results reported by a previous study[5].Importantly,MANEC,associating with a rapid growth pattern in NEC,showed 60% of outward growth,indicating that the higher growth rate of the tumor cells represents this aggressive and infiltrative growth pattern.In our case,colonic and duodenum self-expandable metallic stent(SEMS) were inserted for direct colonial obstruction and infiltrative growth toward the duodenum.Generally,stenting in the gastrointestinal tract for malignant obstruction due to the adenocarcinoma has been reported as an effective and safe strategy with the clinical success rate of 90.5%-95.5%,as well as an adverse event rate of 3.5%-7.6%[8-10].In addition,it is extremely rare to find out the tumor perforation,following the stent placement with the rate of 2% that might occur at the necrotic tissue of the tumor[11].The main reason of the tumor perforation following SEMS insertion in our case is likely due to the rapid growth of the NEC tumor cells at both inside and outside the colon,evidenced by the tumor necrosis appeared in the endoscopic findings and 90% of positive cells by Ki67 staining that led to the vulnerability of the mass structure.As successful induction of the chemotherapy could lead to the better survival period (Table 2),stenting is of great importance to manage the symptoms and QOL.The summary of the chemotherapy induced in the recent cases are summarized in Table 2[7,12-68].As shown in Table 2,24 NEC patients received platinum-based chemotherapy and 11 NEC patients received 5-FU-based chemotherapy as the first-line regimen.In particular,9 MANEC patients received 5-FU-based chemotherapy,and only 1 patient received platinum-based chemotherapy,probably targeting the component of adenocarcinoma.The responses to the platinumbased and 5-FU-based chemotherapy were (CR,2;PR,7;stable disease (SD),3;and progressive disease (PD),11;and (CR,0;PR,3;SD,2;and PD,6),respectively.Therefore,development of an effective chemotherapy-based regimen is essential as well.

    Figure1 Imaging findings.

    Consequently,exertion is essential to detect NEC in early stage,thereby the correct diagnosis is of great importance,while NEC and MANEC are frequently misdiagnosed as adenocarcinoma or another malignant tumor at the first imaging or histological study[5].Thus,to diagnose accurately,detailed endoscopic observation and histological research are required.A study suggested that fluorodeoxyglucose positron emission tomography (FDG-PET) associates with high-sensitivity to tumor,as well as high-proliferation (e.g.,NEC)[12],therefore FDG-PET is precious to diagnose tumor with clinical feature of NEC.

    Figure2 Histological findings of the tumor.

    At present,early diagnosis followed by the surgical resection is the most favorable clinical course for better prognosis,and if impossible,careful making decision for chemotherapy and stenting for obstruction is significant.Furthermore,NEC with higher cell proliferation not only may cause the intestinal obstruction,but also the invasive growth to the surrounding organs,leading to the tumor rupture after stenting inside the tract,thus careful consideration is essential for making a right clinical decision.In particular,the placement of stent needs to be highly taken into account as it is significantly different from the colorectal adenocarcinoma in terms of the cell growth pattern,and clinical characteristics.

    CONCLUSION

    As a result,as the rapid growth pattern of NEC is difficult to be managed,early diagnosis and careful management with the understanding of the disease are essential.However,accumulated data related to this rare disease may assist physicians to effectively treat patients with the help of development of chemotherapy,stenting method,as well as upgrading medical devices.We hope that the results of the present study can enhance the information related to NEC and also help the scholars to better understand the disease.

    Table2 Summary of the cases reported to date

    F:Female;M:Male;ECC:Endocrine cell carcinoma;MANEC:Mixed adeno-neuroendocrine carcinoma;NEC:Neuroendocrine carcinoma;SCC:Squamous cell carcinoma;A:Ascending colon;R:Rectum;S:Sigmoid colon;C:Cecum;T:Transverse colon;D:Descending colon;P:Platinum-based chemotherapy;F:5-fluorouracil-based regimen;PD:Progressive disease;CR:Complete response;SD:Stable disease;PR:Partial response.

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