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Clinical Pathological Analysis of Appendiceal Neoplasms From 4800 Appendectomy Specimens

1 Colorectal Research Center, Shiraz University of Medical Sciences, Shiraz, IR Iran
2 Department of Pathology, Shiraz University of Medical Sciences, Shiraz, IR Iran
3 Department of Pathology, Urmia University of Medical Sciences, Urmia, IR Iran
*Corresponding author: Behrooz Ilkhanizadeh, Associate Professor of Pathology, Urmia University of Medical Sciences, Urmia, IR Iran. Tel: +98-9143419194, Fax: +98-7112330724, E-mail:
Annals of Colorectal Research. 2015 September; 2(3): e24927 , DOI: 10.17795/acr-24927
Article Type: Research Article; Received: Oct 28, 2014; Accepted: Oct 30, 2014; epub: Sep 10, 2014; ppub: Sep 1, 2015


Background: Appendiceal Neoplasms are relatively uncommon. Although Carcinoid tumor is the most prevalent tumor of appendix, mucinous tumors and metastatic tumors can also be identified in appendectomy specimens after careful pathologic examination.

Objectives: The main goal of this study is the evaluation of appendectomy specimens for appendiceal neoplasms and subsequent subtyping of those tumors.

Materials and Methods: Retrospective assessment of 4800 appendectomy specimens, performed from 2010 to 2014, was done. The specimens were collected from Namazee and Faghihi hospitals, affiliated to Shiraz University of Medical Sciences. The clinical and histopathologic data were collected and analyzed by satisfactory statistical methods.

Results: The age of patients was 32 years with a male to female ratio of 3:1. The overall incidence of appendiceal neoplasms was 86 in 4800 specimens (1.8%). The most common neoplasm was carcinoid tumor. Others reported tumors were mucinous cyst adenoma, mucocele, mucinous adenocarcinoma, leukemic infiltration, and a case of appendiceal involvement by bladder transitional cell carcinoma.

Conclusions: Although appendiceal tumors are not as prevalent as colon cancer, careful examination of appendectomy specimens can identify neoplastic processes. Beyond carcinoid tumors and mucinous neoplasms, leukemia lymphoma and other metastatic tumors can involve the appendix.

Keywords: Appendix; Appendiceal Neoplasm; Classification

1. Background

The appendix is the most frequent site for developing carcinoid tumors, i.e., tumors with endocrine differentiation that span a wide range of morphologic variety (1). Adenocarcinomas of the appendix also show interesting morphologic variations from those resembling the usual colorectal carcinoma to those arising from a carcinoid or mucinous tumors, which might appear well differentiated and indistinguishable from adenoma and spread widely through the peritoneal cavity (1, 2). The term mucocele is unspecific and its better no to use this term because it tells nothing about the original cause of mucin accumulation while its causes range from a hyperplasia to malignant neoplastic processes. Therefore, mucocele is not an entity and few authors use it at present (3). The majority of mucinous tumors of appendix are benign, i.e., mucinous cystadenomas. These types of tumors are lined by tall columnar mucin containing epithelial cells with atypical changes. Some of these tumors might arise from previous hyperplastic polyps (4). The malignant counterpart, namely, mucinous cystadenocarcinoma, might have similar or even the same microscopic features. There are two criteria for malignancy:

invasion of the wall of appendix by atypical glands and

identification of neoplastic epithelial cells in the peritoneal cavity (5).

Two recent nomenclature proposals for mucinous neoplasms of appendix might simplify the classification of these tumors. One classification, suggested by Misdraji et al. is as follows:

Low grade mucinous neoplasms when the cells are well-differentiated and noninvasive and

mucinous adenocarcinoma, when cells are highly atypical and/or invasive (5).

Another classification by Pai et al. suggests the following:

mucinous adenoma when tumor is confined to appendix;

low grade mucinous neoplasm with low risk of recurrence when a cellular peritoneal deposits are present;

low grade mucinous neoplasm with high risk of recurrence have low grade cytological atypia but are accompanied by extra-appendiceal neoplastic epithelium; and

mucinous adenocarcinoma when invasion or high grade cytology present. Other common neoplasms of appendix are neuroendocrine tumors, which are sub classified into classic carcinoid tumors and goblet cell carcinoids.

They are found in about one of every 300 routine appendectomies correct. About 70% of these tumors are located at the tip of appendix. Other neoplasms of appendix include GIST, lymphomatous involvement, Kaposi sarcoma, and metastatic tumors (6, 7).

2. Objectives

The study is designed to survey 4800 appendectomy specimens from Namazee and Faghihi hospitals affeliated to Shiraz University of Medical Sciences. Appendiceal tumor prevalence will be identified and then subtyping of these neoplasms will be done.

3. Materials and Methods

A retrospective histopathologic review of appendectomy specimens, which were performed from 2010 to 2014 in Namazee and Faghihi hospitals affiliated to Shiraz University of Medical Sciences, Shiraz, Iran, was conducted. Clinical as well as histopathologic data including macroscopic findings and microscopic examination from hematoxylin and eosin (H and E) staining were collected. The sections were prepared according to a standard procedure and included one longitudinal section from the tip and two circular sections from the center and proximal part of appendix. In the cases with additional gross histopathological abnormalities, especially when a tumoral mass was presented, at least three sections from mass were added to previous sections and surgical resected margins were embedded. The slide were stained with H and Emethod and reviewed by one expert pathologist. Any histopathologic findings include inflammatory or neoplastic changes were recorded. In the patients with appendiceal neoplasms, important data including the type of tumor, depth of invasion, lymph vascular invasion, presence of necrosis, degree of cytological atypia, and histopathologic changes of nontumoral parts of appendix were collected. Patients with confirmed appendiceal neoplasms were included. All primary or secondary as well as benign or malignant neoplasms were included. Histopathological reports of neoplasm without available HandE staining were excluded.

Patients were distributed into following subgroups:

carcinoid tumor;

benign mucinous tumor;

mucinous adenocarcinoma;

leukemic or lymphomatous involvement; and

metastatic tumor.

3.1. Statistical Analysis

All data were collected and analyzed by SPSS version 17 (SPSS Inc., Chicago, IL, USA). The differences between the subgroups was evaluated by one-way ANOVA with subsequent multiple comparison by Pearson's test. Differences between the groups were considered significant if P value was < 0.05 in a two-sided test.

4. Results

All consecutive appendectomy specimens between January 2010 and July 2014 were studied. The total appendectomies were 4800 of which 86 patients had appendiceal tumor (1.8%). The mean age at presentation was 32 + 8.64 years with a male to female ratio of 3:1. The most common appendiceal tumor was classic carcinoid, detected in 37 specimens (43%), following by benign mucinous tumors in 30 (34.8%) and adenocarcinoma in 12specimens (14%). There were sixcases of leukemia lymphoma (7%) and onemetastasis from bladder transitional cell carcinoma (1.2%). The most common clinical presentation was acute abdomen followed by nonspecific abdominal pain and incidental finding during radiologic investigation for other reasons. The primary and metastatic malignant tumors presented at older age than benign tumor did (P > 0.05). Most of patients with appendiceal adenocarcinoma were male. Acute surgical abdomen was more frequently seen with benign tumors than with malignant ones. The latter presented with nonspecific clinical presentation or showed tumor-related symptoms such as weight loss or anemia. The histopathologic findings in various types of appendix tumors were studied and recorded. The most common neoplasms of appendix in this study were classic carcinoid tumors, which showed neoplastic endocrine cells with nesting or trabecular pattern. They were composed of uniform cells with fine chromatin without necrosis or mitosis (Figure 1). Benign mucinous tumors showed both mucinous cyst adenoma and in some cases only acellular mucin lakes (Figure 2). Burkitt's lymphoma was been the most common type of lymphomatous involvement of appendix (Figure 3). The Figure 4 shows a case of adenocarcinoma of appendix.

Figure 1.
Nests of Endocrine Cells With Uniform Benign Looking Nuclei, HandE staining, magnification × 400

Figure 2.
Benign Mucinous Tumors Showing Acellular Mucin Lakes or Presented as Mucinous Cyst adenomas (a, b)

Figure 3.
Burkett's Lymphoma was the Most Common Type of Lymphomatous Involvement of Appendix (a, b)

Figure 4.
The Appendiceal Adenocarcinoma Presented as Invasion of Neoplastic Glands through the Wall of Appendix into the Muscular is Propria

5. Discussion

Tumors of appendix are uncommon and most often diagnosed unexpectedly in emergency conditions. The most common tumor is classic carcinoid tumor. They are found in one of every 300 appendectomies (8-10). Moertel et al. studied 144 cases of classic carcinoid tumors and showed that 70% were located at the tip of appendix, 23% in the body, and 7% at the base. The size of tumor were less than 1cm in 70% of the cases (11). The appendiceal carcinoid is most often benign and in contrast to gastric endocrine tumors, metastasis is rare. The tumor size is proportional to the risk for metastatic disease (12, 13). The calculated risk of metastasis from tumors < 1 cm is zero, while a definite increase occurs with a tumor size is > 2 cm, with a metastasis rate of 20% (14, 15). Most of the mucinous tumors of appendix are benign. The classification of these tumors has been revised recently by two proposals suggested by Misdraji et al. and Pai et al. (16, 17). The term mucocele stands for a wastebasket and should not be used anymore because there are wide varieties of benign and malignant lesions that can produce mucocele. Primary adenocarcinoma of appendix is a rare entity. It can be located in any part of the appendix. The microscopic appearance often resembles colon adenocarcinoma and refers to as colonic type. Some of adenocarcinomas are mixed with carcinoid tumor (carcinoma with neuroendocrine differentiation) (18). Malignant lymphoma leukemia, especially Burkett's lymphoma, usually involves the appendix. In the present study, we studied all appendectomy specimens from two large centers for appendiceal tumors. The interesting finding was the high incidence of lymphomatous involvement of appendix. Overall, these neoplasms composed 5% of appendiceal tumors. The Burkett's lymphoma, which is a high-grade B-cell tumor, was the most common appendiceal lymphomatous involvement. They usually presented with nonspecific symptoms or might present at emergency department with acute abdomen. Most of the cases were children under age of 15 years and the tumors were accompanied by mesentric and para-aortic lymphadenopathy. Most of the carcinoid tumors had small size of < 2cm in diameter and none of them showed metastasis. Carcinoid syndrome was not seen in the present study and the detected tumors were non-secretory. Adenocarcinomas were colonic type and treated with right hemicolectomy. The mucocele and benign mucinous tumors were classified according to Pai et al. (17) proposal. They were benign tumors treated with appendectomy. The most important limitation of this study was lack of long-term follow-up of the patient to determine their survival. Table 1 shows the charactristics and clinical findings of various subtypes of appendiceal neoplasms. The most common appendix neoplasm was been carcinoid followed by benign mucinous tumors. The interesting finding was appendiceal lymphomatous involvement which most commonly seen among children

Table 1.
Characteristics and Clinical Presentation of Histopathologic Subgroups a


Authors’ Contributions: Massood Hosseinzadeh: data collecting, writing and final editing; Mohammad Hossein Anbardar: Data collecting; Mahammad. Mohammadianpanah: primary idea and consulting; and Behrooz Ilkhani: corresponding author.
Funding/Support: The study was financially supported by Shiraz University of Medical Sciences.


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Table 1.

Characteristics and Clinical Presentation of Histopathologic Subgroups a

Carcinoids BMT AC LL MET
No. (%) 37 (43) 30 (34.8) 12 (14) 6 (7) 1 (1.2)
Age, y 25 35 51 12 60
Male toFemale Ratio 2:1 2:1 2:1 1:1 -
Clinical Presentation, %
Acute Abdomen 62 50 32 20 -
Nonspecific 22 15 10 45 -
Incidentaloma 10 25 35 12 -
Tumor-Related 6 10 23 23 100
a Abbreviations: BMT, benign mucinous tumor; AC, adenocarcinoma; LL, lymphoma leukemia; and MET, metastasis

Figure 1.

Nests of Endocrine Cells With Uniform Benign Looking Nuclei, HandE staining, magnification × 400

Figure 2.

Benign Mucinous Tumors Showing Acellular Mucin Lakes or Presented as Mucinous Cyst adenomas (a, b)

Figure 3.

Burkett's Lymphoma was the Most Common Type of Lymphomatous Involvement of Appendix (a, b)

Figure 4.

The Appendiceal Adenocarcinoma Presented as Invasion of Neoplastic Glands through the Wall of Appendix into the Muscular is Propria