|Ahead of print
Appendiceal neoplasms: Suspected findings and reports of 14 cases
Serhan Yilmaz, Hakan Bolukbasi
University of Health Sciences, Kanuni Sultan Süleyman Training and Research Hospital, General Surgery, Istanbul, Turkey
|Date of Submission||29-Sep-2020|
|Date of Decision||08-Oct-2020|
|Date of Acceptance||24-Jan-2021|
|Date of Web Publication||29-Jun-2022|
University of Health Sciences, Kanuni Sultan Süleyman Training and Research Hospital, General Surgery, Istanbul
Source of Support: None, Conflict of Interest: None
Background: Neoplastic lesions of the vermiform appendix are still considered to be rare, some studies suggest that appendix cancer may be on the rise, with an estimated incidence of 0.08–0.1% of all appendiceal specimens. The lifetime incidence of malignant appendiceal tumors ranges from 0.2 to 0.5%.
Patients and Methods: Our study is applied at the Department of General Surgery at tertiary training and research hospital; 14 patients who had appendectomy or right hemicolectomy between December 2015 and April 2020 were evaluated.
Results: The mean age of the patients was 52.3 ± 15.1 (range, 26–79) years. Gender of the patients were: five (35.7%) men and nine (64.3%) women. The clinical diagnosis was appendicitis without suspected findings in 11 (78.6%), appendicitis with suspected findings (appendiceal mass, etc.) in three (21.4%) of the patients, and there is no patient with asymptomatic or other rare findings. Surgeries applied for the patients were: nine (64.3%) underwent open appendectomy, four (28.6%) underwent laparoscopic appendectomy, and one (7.1%) underwent open right hemicolectomy. Histopathologic results were as follows: five (35.7%) neuroendocrine neoplasm, eight (57.1%), noninvasive mucinous neoplasm, and one (7.1%) adenocarcinoma.
Conclusion: While diagnosis and management of appendiceal pathology, surgeons should be familiar with suspected findings of appendiceal tumors and discuss them with patients to the possibility of histopathologic results.
Keywords: Appendectomy, appendix cancer, right hemicolectomy
Appendix tumor should be kept in mind in the differential diagnosis of patients operated on for acute appendicitis.
| » Introduction|| |
Although the appendix usually presents with inflammatory diseases, it rarely becomes cancerous. The incidence of appendicitis requiring emergency surgical treatment is common, with appendectomy being used as the standard treatment since 1889. Neoplastic lesions of the vermiform appendix are still considered rare, and some studies suggest that malignant tumors may be on the rise, with an estimated incidence of 0.08–1.4% of all appendectomies performed to treat acute appendicitis. However, recent studies have demonstrated an elevated incidence of malignancies, ranging from 5.9 to 12%, in patients with complicated appendicitis (appendiceal mass, etc.). The lifetime incidence of malignant appendiceal tumors ranges from 0.2 to 0.5%. Graham et al. reviewed 6,824 surgical specimens of vermiform appendices and found 42 primary epithelial tumors, yielding a prevalence rate of approximately 0.62%, with subjects having a mean age of 45.9 ± 19.3 years and a men-to-women ratio of 1:1. Usually, neuroendocrine neoplasms, noninvasive tumors, and carcinomas comprise the majority of these tumors, with reported incidences of 47.6, 45.2, and 7.14%, respectively. Less commonly, lymphomas and sarcomas can also affect the appendix, with respective incidences of 1.7 and <1%.
| » Patients and Methods|| |
By reviewing the pathological database, between December 2015 and April 2020 in tertiary training and research hospital, 14 patients had primary appendiceal neoplasm. Patient demographics and clinical and pathological characteristics are presented in [Table 1]. Frequency and percentage for categorical variables and mean and standard deviation values for continuous variables are given. All analyses were performed using the Social Sciences Statistics Package (version 22.0) for Windows (SPSS Inc., Chicago, Illinois, USA).
|Table 1: Patient demographics, clinical, and pathological characteristics|
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| » Results|| |
Among 2498 patients who underwent appendectomy between 2015 and 2020, appendiceal neoplasms were detected in 14 (0.56%) patients. The main cause of referral to the hospital was right lower abdominal pain, anorexia, nausea, and vomiting. Leukocytosis and high C-reactive protein levels were observed in all the patients. Noncomplicated appendicitis (without suspected signs) was diagnosed in 11 (78.6%) patients, and complicated appendicitis (with suspected signs) was diagnosed in 3 (21.4%) patients according to radiologic studies (ultrasonography, computerized tomography). The mean age at diagnosis was 52.3 ± 15.1 years (range, 26–79 years), and the mean tumor size was 0.6 ± 0.3 cm (range, 0.1–1.2 cm). Of the patients, nine (64.2%) were women and five (35.8%) were men. An appendectomy was performed in 13 (92.9%) patients, and right hemicolectomy was performed in 1 (7.1%) patient because of suspected mesoappendix invasion. Tumor size, localization, and invasion depth are shown in [Table 2].
| » Discussion|| |
Primary malignant tumors of the appendix are rare, occurring in 0.5% (0.09–1.4%) of all appendectomies. Appendiceal neoplasms (mostly benign) maybe asymptomatic and discovered incidentally on physical examination or imaging studies. These types of patients have increased in frequency due to the increased use of abdominal ultrasonography, computed tomography, positron emission tomography, and serum tumor markers for patient follow-up and screening. Appendiceal neoplasms (mostly malignant) cause symptoms related to local inflammation and invasion, perforation, bleeding, mass effect, lymph node involvement, peritoneal spread, or metastatic disease. The most frequent initial manifestation of appendiceal neoplasm is acute appendicitis, seen in 30% to more than 50% of patients. On the other hand, the incidence of appendiceal tumors in appendectomy specimens from patients who underwent surgery due to acute appendicitis ranges from 0.9 to 1.7%, and regardless of the pathologic etiology, the most common presentation of appendiceal neoplasm is acute appendicitis. The patient's history and physical examination that should raise the suspicion of an appendiceal tumor in appendicitis presentation include advanced age (older than 50 years), a family history of colon cancer or inflammatory bowel disease, outpatient steroid or immunosuppressant use, unexplained anemia, the absence of migratory or chronic right lower quadrant pain, and a palpable right quadrant mass. In imaging studies, appendix diameter >15 mm (or 20 mm) or characteristics of cystic dilatation with homogeneous low-attenuation material or a soft tissue mass in the absence of appendiceal wall thickening (i.e., <6 mm), or ovoid or pear-shaped cystic mass with echogenic layers (“onion skin”) and acoustic shadowing from mural calcifications, irregular and nodular appendiceal wall thickening, adjacent fat stranding or complicated appendicitis appearance (phlegmon, abscess, mass, free fluid, etc.), lymphadenopathy, invasion findings of adjacent structures, metastatic imaging findings (liver, etc.), submucosal mass in the distal appendix, which enhances significantly with or without calcifications should also raise suspicion for a neoplastic process [Table 3]. In our study, there was irregular and nodular appendiceal wall thickening according to BT in three patients. The mean age of the patients was 52.3 ± 15.1 years.
Appendiceal neoplasms can be broadly described as epithelial (e.g., adenomas or adenocarcinomas) and nonepithelial (e.g., neuroendocrine or lymphoma). The epithelial group is often further subdivided based on mucin production, because mucinous neoplasms have distinctly different biological behavior and oncologic outcomes from nonmucinous neoplasms. Retrospective reviews of appendectomy specimens have reported the prevalence of all cases of neuroendocrine neoplasms to be between 57 and 80% of appendiceal tumors, and malignant neuroendocrine tumors represent 11% of malignant tumors. Within the adenocarcinoma malignancies, there are three subtypes: mucinous (37–55%), colonic type (27–34%), and adenocarcinoid (11–19%) also called Goblet cell carcinoid, which has features of both carcinoid tumor and mucinous adenocarcinoma. Patients with appendiceal carcinoma have a notable risk of developing a synchronous colorectal neoplasm, which was highest in patients with mucinous adenocarcinoma and should be followed because a second malignancy will develop in 15–20% of cases. Common benign tumors include villous adenomas and mucinous cystadenomas., Once encountered, the management of appendiceal tumors changes patient management from that of traditional causes of appendicitis, while in multiple types of modern imaging studies, the majority of cases of appendiceal neoplasms are not diagnosed preoperatively, but rather intraoperatively, or usually on pathologic review of the specimen postoperatively, as our study has shown.
General surgeons should be familiar with acute appendicitis with suspicious findings of appendiceal neoplasm and prepared for proper treatment both intraoperatively and retrospectively when diagnosis is made based on the pathologic specimen. Exploration of the abdomen and inspection of the surgical specimen by the surgeon during appendectomy may reveal atypical findings. A frozen section should be performed whenever appendiceal findings are atypical. A diagnosis of malignancy can be made during surgery, and appropriate surgery can be performed. Treatment then varies depending on the tumor type and location.
Surgery for neuroendocrine tumors is the only curative treatment for appendiceal neuroendocrine tumors (aNETs) and is incurable when there is unresectable metastatic disease. aNETs smaller than 1 cm do not recur or metastasize, whereas those between 1 and 2 cm rarely do but above 2 cm may recur or metastasize. The most common metastatic sites are the regional and distant lymph nodes (15.8%), liver (0.6%), lung (0.2%), and bone (0.3%).
Extent surgical resection for nonmetastatic aNETs confined to the appendix is determined by tumor size and histological features. Lesions <1 cm in diameter (80%) and without unfavorable features are adequately treated with appendectomy, taking care to remove the entire mesoappendix and with negative margins that are considered curative and no further staging or postoperative surveillance is necessary. Tumor size >2 cm and mesoappendiceal invasion have been correlated with nodal metastasis, but not with poor outcome. Tumors >2 cm (6%) are best treated with formal right hemicolectomy, because the reported risk of nodal metastases ranges from 20 to 85%. aNETs between 1 and 2 cm in size (14%) have an intermediate risk of nodal metastases in most series., However, the largest clinical series found no nodal disease in primary tumors <2 cm, and some authors recommend appendectomy alone for all lesions under this threshold. In addition to size, histologic features also influence surgical decision-making. Unfavorable findings include tumor invasion beyond the muscularis propria, mesoappendiceal invasion >3 mm, tumor at the base of the appendix with positive margins or involvement of the cecum, lymph node involvement, advanced grade consisting of a raised tumor prognostic index as measured by mitotic index (>2 mitoses per high-power field) or Ki-67 index (>3%), cellular pleomorphism with a high mitotic index, and lymphatic or vascular invasion. Decision making for right hemicolectomy in small-and intermediate-sized aNETs should be made on a case-by-case basis, with consideration given to unfavorable findings and patient comorbidities and preferences. At presentation, consideration for surgical treatment is reasonable if the metastatic lesion or lesions are limited and resectable., Some surgeons suggest that appendectomy is sufficient and recommended hemicolectomy in those patients where it is necessary to clear the tumor or perform complete cytoreduction; demonstrated lymph node involvement; or a nonmucinous subtype. However, it has been generally accepted that right hemicolectomy is the preferred surgical intervention for all subtypes of adenocarcinoma. Many studies have shown that there is a clear survival benefit with the addition of hemicolectomy. The prognosis of adenocarcinoma depends on the subtype and extent of the disease. While mucinous adenocarcinoma is considered to have a more favorable prognosis, Goblet cell subtype is considered to have a worse prognosis with a 55–80% 5-year survival rate., In our study, there were five patients in the aNETs group. In these cases, the tumor size was less than 1 cm, and there was no mesoappendix or lymph node involvement in the pathology reports. These patients were not given any other treatment in addition to appendectomy.
In patients with mucinous adenocarcinoma, regardless of size, it is important to remove the appendix or cyst en bloc with a negative margin and without mucin spillage into the peritoneal cavity. Appropriate initial surgical management is critical because iatrogenic rupture of the appendix can convert the situation from localized to disseminated; therefore, if an unruptured cannot be safely resected laparoscopically, conversion to an open operation is recommended. For localized, non ruptured, low-grade mucinous adenocarcinoma, appendectomy with en bloc resection of the cystic lesion (including the entire mesoappendix with negative margins and no evidence of perforation or peritoneal involvement) is likely curative. If pathology demonstrates high-grade disease that is T2 or greater, right hemicolectomy is typically recommended because of the higher risk of lymph node involvement., In cases where peritoneal dissemination has occurred, whether gross or microscopic, regional metastasis is present and regional therapy is indicated. The optimal therapy is complete surgical cytoreduction (defined as removal of all gross disease or reduction of tumor deposits to≤2.5mm in thickness) in combination with intraperitoneal chemotherapy. Cytoreduction routinely involves complete omentectomy and right lower quadrant peritonectomy. Bilateral oophorectomy is also recommended, especially in postmenopausal women, as the ovaries are a frequent site of metastasis and recurrence if not removed. Women of childbearing age, in the absence of gross disease, may elect to preserve their ovaries.
For patients whose diagnosis was made at appendectomy with pathology showing evidence of rupture or tumor cells outside of the appendix, cross-sectional imaging may not demonstrate any residual disease. In these cases, the assessment of disease burden is best performed by laparoscopy. If there is no gross tumor or mucin identified and pathology shows low-grade mucinous adenocarcinoma, surveillance with examination and cross-sectional imaging is recommended.,
For high-grade tumors with perforation and tumor cells outside the appendix, laparoscopy or laparotomy with assessment for residual disease is warranted, regardless of imaging findings. Complete cytoreduction of any gross residual tumor or mucin should be performed. This typically includes omentectomy and right lower quadrant peritonectomy and may also include bowel resection, splenectomy, cholecystectomy, and salpingo-oophorectomy. Most specialists recommend intraperitoneal chemotherapy. At the time of cytoreduction, right hemicolectomy is used sparingly for low-grade mucinous adenocarcinoma, as lymph node metastasis is rare (6% of cases). In high-grade disease, nodal metastases are present in up to 20% of cases, so right hemicolectomy is a consideration; however, therapeutic benefits have not been demonstrated. Even after complete cytoreduction and intraperitoneal chemotherapy, recurrence of mucinous adenocarcinoma is common in both low- and high-grade diseases. In a recently published large series of patients, the median disease-free survival was 38.1 months for patients with low-grade mucinous adenocarcinoma and 21.6 months for high-grade disease., In our study, there were eight patients who had noninvasive mucinous adenocarcinoma. We performed an appendectomy in these cases. No perforation or peritoneal spread was observed. There was no mesoapendiceal involvement or lymph node invasion in the pathology reports. No additional treatment was required.
In colonic-type adenocarcinoma, if there is no evidence of distant metastasis, right hemicolectomy is recommended, with 12 or more lymph nodes typically considered adequate for accurate staging. The rate of distant metastasis at presentation for colonic-type adenocarcinoma of the appendix is not well known, given the rarity of the disease, but has been reported to be 23–37%. The peritoneum (including ovaries) is the most common site, and liver and lung metastases are less common. Systemic chemotherapy is the recommended treatment for asymptomatic patients who present with distant metastasis. For patients with peritoneal-only metastatic disease, complete cytoreductive surgery and intraperitoneal chemotherapy should be considered if complete tumor debulking can be achieved. In our study, there was a colonic type adenocarcinoma in one patient. We performed right hemicolectomy in this case because mesoappendix and lymph node involvement were present in the pathology report after appendectomy.
| » Conclusion|| |
Diagnosis of appendiceal neoplasm in pathological examination of uncomplicated acute appendicitis is a rare event. However, its incidence in complicated acute appendicitis (mass, etc.) is not negligible (1% versus 12%). Surgeons keep in mind that neoplasm is a rare but serious cause of appendiceal disease and should be prepared for all scenarios.
Ethical policy and institutional review board statement
All procedures performed in this original article were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]