Rectal adenocarcinoma resection specimen with an incidental carcinoid in the resection margin

  • Authors:
    • Jie Zhou
    • Xiaodong Teng
  • View Affiliations

  • Published online on: March 4, 2014     https://doi.org/10.3892/ol.2014.1933
  • Pages: 1661-1664
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Three cases of incidental carcinoid tumors have been identified in the surgical margin of rectal adenocarcinoma resection specimens. In all cases the rectal carcinoids exhibited low‑risk features, such as a tumor size <10 mm, no muscularis propria invasion and no lymph node involvement. No further excision was conducted and the three cases were followed up for 38, 26 and 14 months, respectively. No regional or distant rectal carcinoid recurrence was identified. Occasionally this is inevitable in order to achieve a positive resection margin for the microcarcinoid during the surgical treatment of another malignancy. However, such carcinoids are usually low‑risk and behave less aggressively than same‑site adenocarcinomas. Thus, it appears reasonable to avoid further excision in patients who are undergoing a rectal adenocarcinoma resection that exhibits a positive margin for low‑risk carcinoid tumor.

Introduction

The term carcinoid is synonymous with the term well differentiated neuroendocrine tumor. Recently, carcinoids of the colon and the rectum have been grouped together. However, rectal carcinoids tend to behave less aggressively than colon carcinoids. Rectal carcinoids are often only diagnosed incidentally during routine lower endoscopy procedures due to the fact that such tumors are small, submucosal in location and rarely metastatize (13). In addition, rectal carcinoids are uncommon tumors. The age-standardized incidence of such carcinoids was ~0.3–1.2 cases per 100,000 individuals annually between 1992 and 1999, which has increased in recent decades due to improvements in diagnostic technology (such as endoscopy) and as a result of increased medical awareness (4). Rectal carcinoids tend to grow more slowly than same-site adenocarcinomas and harbor a favorable five-year survival rate. Gastrointestinal carcinoids are associated with a high incidence of second primary malignancy, found to occur in ~13.1% of all rectal carcinoids (4). The identification of an incidental gastrointestinal carcinoid during surgical treatment of another malignancy will usually only require resection without additional treatment, having little effect on prognosis (5). However, the treatment of unexpected carcinoids identified in the surgical margin of rectectomy specimens has not been previously described in any reported literature. In the present study three such cases have been presented and the current literature has been reviewed.

Materials and methods

In total, three pathology reports, which revealed incidental carcinoids in the surgical margin of radical rectectomy specimens were retrieved from the pathology database of The First Affiliated Hospital (Hangzhou, China), from January, 2007 to April, 2013. Clinical details were acquired from medical records retrospectively, such details included patient gender, age, medical history, symptoms at presentation, modality of diagnosis and treatment. The pathological features were identified from the pathology reports and the carcinoid tumor size was reported as the largest diameter that was recorded microscopically. The follow-up was conducted via telephone interview and through examination of laboratory, endoscopy and imaging results that were obtained during clinical visits. The examination results were documented in the laboratory and imaging databases, which were also reviewed. This study was approved by the institutional ethics committee of The First Affiliated Hospital, College of Medicine, Zhejiang University (Hangzhou, China). Informed consent was obtained from the patients families.

Results

Patient and primary adenocarcinoma features

All three patients were male and were aged 62, 66 and 54 years at presentation. They all experienced hematochezia, leading to endoscopic evaluation and biopsy. This resulted in the identification of adenocarcinoma and subsequently a radical rectectomy (Dixon’s operation) was performed. Features of the primary adenocarcinomas are displayed in Table I.

Table I

Features of primary adenocarcinoma.

Table I

Features of primary adenocarcinoma.

CaseHistological typeDifferentiationTumor size (cm)Depth of invasionTNM stage
1AdenocarcinomaIntermediate3.5×3.0Within submucosaT1N0M0
2AdenocarcinomaIntermediate4.0×3.5Within serosaaT3N0M0
3AdenocarcinomaIntermediate4.5×3.5Within adventitiabT3N0M0

a Tumor above peritoneal reflection.

b Tumor under peritoneal reflection.

{ label (or @symbol) needed for fn[@id='tfn3-ol-07-05-1661'] } TNM, tumor node metastasis.

Incidental carcinoid features

The distal margins of the resection specimens were 2–3 cm from the respective adenocarcinoma and were removed during surgical procedures. Sections of each distal margin revealed an unexpected microcarcinoid tumor within it. Their sizes were all <0.5 mm in diameter (0.2, 0.2 and 0.3 mm, respectively). All tumors invaded the submucosa only, without lymphovascular invasion, lymph node involvement or distant metastasis. Immunohistochemical staining was performed on all carcinoid tumors. The tumor cells were identified to be positive for synaptophysin, chromogranin A and cluster of differentiation 56, but were negative for Ki-67 (Fig. 1).

Treatment and follow-up

Following diagnosis, patients were treated without further surgical or endoscopic resection. This decision was made by the patient and was based on the consideration that benign-like carcinoids have little effect on patient prognosis compared with adenocarcinoma. None of the patients underwent chemotherapy or radiation following the radical rectectomy. Patients were followed up for 38, 26 and 14 months, respectively. Case three suffered hepatic metastasis of the adenocarcinoma in the 13th month following the rectectomy and underwent partial resection of the liver. However, none of the three patients demonstrated carcinoid recurrence or metastasis.

Discussion

In 2008, Landry et al (6) proposed a novel staging system for adenocarcinoma based on the assessment of 4,701 rectal carcinoid tumors, considering variables, such as tumor size, depth of invasion, lymph node involvement and distant metastasis. In the study, the five-year survival rates for patients with stage I, II, III or IV disease were 97, 84, 27 and 20%, respectively. Overall, patients with rectal carcinoids exhibit a favorable five-year survival rate (88.3%), as reflected by a large percentage of localized tumors (82%) (4). However, cancer-specific survival rates are comparable between rectal carcinoid and adenocarcinoma if tumors exhibit lymph node or distant metastasis (7). Furthermore, the metastatic rate of early-stage rectal carcinoids may be higher than those of rectal carcinomas if tumors are >10 mm in diameter (7,8).

Certain studies have identified various risk factors hypothesized to be involved in rectal carcinoid metastasis, such as a tumor size >10 mm, muscularis propria infiltration, the presence of lymphovascular invasion, the mitotic rate increased and the Ki-67 index increased (7, 912). Mani et al (3) evaluated >200 studies of rectal carcinoids and noted that tumor size and muscularis propria invasion were the two most important predictors of neoplastic malignancy. The majority of rectal carcinoids are <10 mm at the time of diagnosis with a median size of 6 mm (6). These lesions metastasized in <2% of patients (3). However, when a tumor reaches a size >10 mm, the metastatic rate increases notably. For example, in tumors measuring between 10 and 20 mm, the metastatic rate increases to 10–15%, whereas tumors measuring >20 mm have a metastatic rate of 60–80% (3). Another study showed that metastases were present in only 2% of tumors, which were <20 mm and did not exhibit muscularis propria invasion, compared with 48% in tumors that had invaded the muscularis layer (13). In addition, a large study in Asia revealed that a tumor size of >10 mm and the presence of lymphatic invasion were independently predictive of lymph node metastasis, whereas a tumor size >20 mm and the presence of venous invasion were independently predictive of distant metastasis (7).

Synchronous or metachronous secondary primary malignancies (SPM) are a common observation in carcinoid tumor patients (4,5,1417). In addition, delayed metachronous SPM is common and incidence is eight times higher in carcinoid tumor patients compared with in the normal population (16). Of the gastrointestinal tract carcinoids, it was noted that a high percentage of associated tumors occurred with small intestinal carcinoids (29.0%), whereas a lower percentage was identified with rectal carcinoids (13.1%) (4). The majority of associated secondary malignancies were found to be located in the gastrointestinal tract (4,5,1417), which occurred in 32–62% of tumors, followed by the genitourinary tract and the lung/bronchial system.

The etiology of this associated high risk of SPM remains unclear. It may be hypothesized that neuroendocrine factors secreted by carcinoids enhance the development or growth of other neoplastic tissue (18). In support of this hypothesis, higher levels of neuroendocrine factors are observed in small intestinal carcinoids (midgut) when compared with colorectal carcinoids (hindgut), in which SPMs are less common. However, it is difficult to explain the high incidence of delayed SPM following excision of carcinoid tumors. It is also speculated that carcinoid patients may exhibit an increased susceptibility to all forms of malignancy (16).

It is generally accepted that rectal carcinoids >20 mm in size require radical resection (1922) due to the high rate of metastases (in ~3/4 cases) as described in the literature (13,14). However, controversy remains with regards to the management of tumors measuring <20 mm. For small rectal tumors (<10 mm), local removal is considered to be sufficient (20,22). However, certain tumors, including those measuring <5 mm, metastasize regionally and distally (7,8,23,24). In general, small rectal carcinoids are known as tumors with little metastatic risk, rendering local treatment desirable and reserving radical surgery for patients that display risk factors that are associated with metastasis. However, the aforementioned risk factors are difficult to identify during preoperative evaluation. In addition, the clinical role of preoperative imaging remains uncertain. Currently, treatment of small rectal carcinoids remains controversial as tumors measuring between 10 and 20 mm demonstrate unpredictable behavior and metastatic risk (20). However, it is reasonable to perform radical rectal resection for tumors, which are 10–20 mm in size and exhibit high-risk features, such as muscular and lymphovascular invasion (7,24).

The necessity for achieving a microscopically negative margin has been questioned in the past (25). Currently it is recommended that a negative margin is to be achieved if possible (2426). Reasons for this are as follows: i) Malignancy criteria for rectal carcinoid are not well established and numerous benign-like tumors may evolve over a prolonged period of time resulting in late recurrences (24,27); ii) once a tumor has spread, chemotherapy and radiotherapy are not effective (19); whereas complete resection of the local disease offers the only chance of a cure; and iii) residual tumors may continue to release factors that enhance the development or growth of other neoplastic tissue.

The identification of an incidental gastrointestinal carcinoid during the operative treatment of another malignancy does not worsen the prognosis of the individual; complete resection is sufficient for therapy (5). However, occasionally it is difficult to identify minute rectal carcinoids during operative treatment of another malignancy, rendering a positive resection margin possible for the microcarcinoid. In the present study, no recurrence of carcinoids were observed in any of the three cases; however, during the follow-up period one patient suffered hepatic metastasis of adenocarcinoma in the 13th month following rectectomy. This indicated that it is reasonable to conduct a follow-up without further excision as such incidental microcarcinoids are usually absent of risk factors and are unlikely to recur prior to another malignancy.

Examination following resection of small rectal carcinoids is controversial. The latest consensus with regards to treatment guidelines for small rectal carcinoids is that tumors without lymph node involvement require no long-term follow up (21,22); however, exceptions do exist. Kwaan et al (24) reported that two patients with small rectal carcinoid tumors presented distant metastasis in the 5th and 13th year after resection. Conversely, small rectal carcinoids are usually treated by local excision at first, which renders it difficult to determine whether there is any lymph node involvement. In addition, synchronous or delayed SPM is a common finding in patients with carcinoid tumors. Thus, certain individuals may argue that long-term follow-up is recommended for delayed metastasis and secondary malignancies with a central point of focus on the gastrointestinal tract (17).

In conclusion, patients with rectal carcinoids, in particular those that are low-risk, have a favorable five-year survival rate. Such carcinoids behave less aggressively than same-site adenocarcinomas. Furthermore, the identification of an incidental rectal carcinoid during operative treatment of another malignancy is possible. However, it is possible to forgo further excision as incidental carcinoids are usually absent of risk factors and are unlikely to recur prior to another malignancy.

References

1 

Shields CJ, Tiret E and Winter DC; International Rectal Carcinoid Study Group. Carcinoid tumors of the rectum: a multi-institutional international collaboration. Ann Surg. 252:750–755. 2010. View Article : Google Scholar

2 

Yoon SN, Yu CS, Shin US, et al: Clinicopathological characteristics of rectal carcinoids. Int J Colorectal Dis. 25:1087–1092. 2010. View Article : Google Scholar

3 

Mani S, Modlin IM, Ballantyne G, Ahlman H and West B: Carcinoids of the rectum. J Am Coll Surg. 179:231–248. 1994.

4 

Modlin IM, Lye KD and Kidd M: A 5-decade analysis of 13,715 carcinoid tumors. Cancer. 97:934–959. 2003. View Article : Google Scholar

5 

Gerstle JT, Kauffman GL Jr and Koltun WA: The incidence, management, and outcome of patients with gastrointestinal carcinoids and second primary malignancies. J Am Coll Surg. 180:427–432. 1995.

6 

Landry CS, Brock G, Scoggins CR, et al: A proposed staging system for rectal carcinoid tumors based on an analysis of 4701 patients. Surgery. 144:460–466. 2008. View Article : Google Scholar

7 

Konishi T, Watanabe T, Kishimoto J, Kotake K, Muto T and Nagawa H; Japanese Society for Cancer of the Colon and Rectum. Prognosis and risk factors of metastasis in colorectal carcinoids: results of a nationwide registry over 15 years. Gut. 56:863–868. 2007.

8 

Soga J: Early-stage carcinoids of the gastrointestinal tract: an analysis of 1914 reported cases. Cancer. 103:1587–1595. 2005. View Article : Google Scholar

9 

Fujimoto Y, Oya M, Kuroyanagi H, Ueno M, Akiyoshi T, Yamaguchi T and Muto T: Lymph-node metastases in rectal carcinoids. Langenbecks Arch Surg. 395:139–142. 2010. View Article : Google Scholar

10 

Fahy BN, Tang LH, Klimstra D, Wong WD, Guillem JG, Paty PB, Temple LK, Shia J and Weiser MR: Carcinoid of the rectum risk stratification (CaRRs): a strategy for preoperative outcome assessment. Ann Surg Oncol. 14:1735–1743. 2007. View Article : Google Scholar

11 

Hassan MM, Phan A, Li D, Dagohoy CG, Leary C and Yao JC: Risk factors associated with neuroendocrine tumors: A U.S.-based case-control study. Int J Cancer. 123:867–873. 2008. View Article : Google Scholar

12 

Hemminki K and Li X: Incidence trends and risk factors of carcinoid tumors: a nationwide epidemiologic study from Sweden. Cancer. 92:2204–2210. 2001. View Article : Google Scholar : PubMed/NCBI

13 

Naunheim KS, Zeitels J, Kaplan EL, et al: Rectal carcinoid tumors - treatment and prognosis. Surgery. 94:670–676. 1983.PubMed/NCBI

14 

Soga J: Carcinoids of the rectum: an evaluation of 1271 reported cases. Surg Today. 27:112–119. 1997. View Article : Google Scholar

15 

Tichansky DS, Cagir B, Borrazzo E, et al: Risk of second cancers in patients with colorectal carcinoids. Dis Colon Rectum. 45:91–97. 2002. View Article : Google Scholar

16 

Schneider C, Wittekind C and Köckerling F: An unusual incidence of carcinoid tumors and secondary malignancies. Chirurg. 66:607–611. 1995.(In German).

17 

Li AF, Hsu CY, Li A, Tai LC, Liang WY, Li WY, Tsay SH and Chen JY: A 35-year retrospective study of carcinoid tumors in Taiwan: differences in distribution with a high probability of associated second primary malignancies. Cancer. 112:274–283. 2008.

18 

Oberg K: Expression of growth factors and their receptors in neuroendocrine gut and pancreatic tumors, and prognostic factors for survival. Ann NY Acad Sci. 733:46–55. 1994. View Article : Google Scholar

19 

Modlin IM, Kidd M, Latich I, et al: Current status of gastrointestinal carcinoids. Gastroenterology. 128:1717–1751. 2005. View Article : Google Scholar : PubMed/NCBI

20 

Ramage JK, Ahmed A, Ardill J, et al; UK and Ireland Neuroendocrine Tumour Society. Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours (NETs). Gut. 61:6–32. 2012. View Article : Google Scholar

21 

Anthony LB, Strosberg JR, Klimstra DS, et al; North American Neuroendocrine Tumor Society (NANETS). The NANETS consensus guidelines for the diagnosis and management of gastrointestinal neuroendocrine tumors (nets): well-differentiated NETS of the distal colon and rectum. Pancreas. 39:767–774. 2010. View Article : Google Scholar

22 

Ramage JK, Goretzki PE, Manfredi R, et al; Frascati Consensus Conference participants. Consensus guidelines for the management of patients with digestive neuroendocrine tumours: well-differentiated colon and rectum tumour/carcinoma. Neuroendocrinology. 87:31–39. 2008. View Article : Google Scholar

23 

Seow-Cheoen F and Ho J: Tiny carcinoids may be malignant. Dis Colon Rectum. 36:309–310. 1993. View Article : Google Scholar

24 

Kwaan MR, Goldberg JE and Bleday R: Rectal carcinoid tumors: review of results after endoscopic and surgical therapy. Arch Surg. 143:471–475. 2008. View Article : Google Scholar

25 

Moore JR, Greenwell B, Nuckolls K, et al: Neuroendocrine tumors of the rectum: a 10-year review of management. Am Surg. 77:198–200. 2011.PubMed/NCBI

26 

Koura AN, Giacco GG, Curley SA, et al: Carcinoid tumors of the rectum: effect of size, histopathology, and surgical treatment on metastasis free survival. Cancer. 79:1294–1298. 1997. View Article : Google Scholar

27 

Sippel RS and Chen H: Carcinoid tumors. Surg Oncol Clin N Am. 15:463–478. 2006. View Article : Google Scholar

Related Articles

Journal Cover

May-2014
Volume 7 Issue 5

Print ISSN: 1792-1074
Online ISSN:1792-1082

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Zhou J and Zhou J: Rectal adenocarcinoma resection specimen with an incidental carcinoid in the resection margin. Oncol Lett 7: 1661-1664, 2014
APA
Zhou, J., & Zhou, J. (2014). Rectal adenocarcinoma resection specimen with an incidental carcinoid in the resection margin. Oncology Letters, 7, 1661-1664. https://doi.org/10.3892/ol.2014.1933
MLA
Zhou, J., Teng, X."Rectal adenocarcinoma resection specimen with an incidental carcinoid in the resection margin". Oncology Letters 7.5 (2014): 1661-1664.
Chicago
Zhou, J., Teng, X."Rectal adenocarcinoma resection specimen with an incidental carcinoid in the resection margin". Oncology Letters 7, no. 5 (2014): 1661-1664. https://doi.org/10.3892/ol.2014.1933