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Background

This is a rare carcinoma. It's importance lies in the treatment considerations as well as its association with conditions such as pseudomyxoma peritonei.

OUTLINE

Epidemiology  
Disease Associations  
Pathogenesis  
Laboratory/Radiologic/Other Diagnostic Testing  
Gross Appearance and Clinical Variants  
Histopathological Features and Variants  
Special Stains/
Immunohistochemistry/
Electron Microscopy
 
Differential Diagnosis  
Prognosis  
Treatment  
Commonly Used Terms  
Internet Links  

EPIDEMIOLOGY CHARACTERIZATION
SYNONYMS  


Appendiceal tumors: retrospective clinicopathologic analysis of appendiceal tumors from 7,970 appendectomies.

Connor SJ, Hanna GB, Frizelle FA.

Department of Surgery, Christchurch Hospital, New Zealand.

Dis Colon Rectum 1998 Jan;41(1):75-80 Abstract quote

BACKGROUND: Appendiceal tumors are rare and often unexpectedly discovered in an acute situation, in which decision-making is difficult. To help define the most appropriate management, a retrospective analysis was undertaken to describe the clinicopathologic behavior of appendiceal tumors, and the literature was reviewed of the management of the different types of appendiceal tumors.

METHOD: From a single center, a histopathologic database of 7,970 appendectomies, all appendiceal tumors, were identified and case notes reviewed. Analysis of clinical presentation, histopathology, operation, and outcome is presented.

RESULTS: During a 16-year period (7,970 appendectomies), 74 patients (0.9 percent) with appendiceal tumors were identified: 42 carcinoid, 12 benign, and 20 malignant. Acute appendicitis was the most common presentation (49 percent), and 9.5 percent were incidental findings. Primary malignant tumors of the appendix were found in 0.1 percent of all appendectomies. Secondary malignant disease was identified in the appendix of 11 patients, most commonly (55 percent) from patients with primary colorectal disease. There was a high incidence of synchronous and metachronous colorectal cancer in all appendiceal tumors: carcinoids, 10 percent; benign tumors, 33 percent; secondary malignancies, 55 percent; primary malignancies, 89 percent.

CONCLUSION: Appendiceal tumors are uncommon and most often present as appendicitis. Most are benign and can be managed by appendectomy, except adenocarcinomas and carcinoids larger than 2 cm, which are most appropriately managed by right hemicolectomy. A suggested management algorithm is provided. Controversy exists over the management of carcinoids 1 to 2 cm in size and adenocarcinoids. All types of appendiceal tumors have a high incidence of synchronous and metachronous colorectal cancer.


Adenocarcinoma of the vermiform appendix. A population study.

Nielsen GP, Isaksson HJ, Finnbogason H, Gunnlaugsson GH.

Department of Pathology, University of Iceland, Reykjavik.

APMIS 1991 Jul;99(7):653-6 Abstract quote

We report seven cases of adenocarcinoma of the vermiform appendix occurring in Iceland during 1974-1989.

The patients ranged in age from 25-83 years, mean age 55.1 years. There were five males and two females. Five had mucinous adenocarcinoma, two had adenocarcinoma. Four patients presented with symptoms and signs of acute appendicitis and all had surgically resectable disease. Three of these patients were alive with no evidence of disease four months, two years and 15 years after presentation; one death of disease occurred seven years after ileocecal resection. In three cases, the clinical presentation was that of metastatic adenocarcinoma of unknown origin. Of these patients two were diagnosed at autopsy and one after appendectomy for perforated appendicitis. Survival in this group was six weeks, three months and twelve months, respectively. In none of our patients was the diagnosis made preoperatively and no tumors were found in appendices removed incidental to other intra-abdominal operations.

The incidence of adenocarcinoma of the vermiform appendix in Iceland during 1974-1989 was approximately 0.2 cases/100.000/year.

 

DISEASE ASSOCIATIONS CHARACTERIZATION
PSEUDOMYXOMA PERITONEI  

 

PATHOGENESIS CHARACTERIZATION
GENERAL  


Epithelial Neoplasms of the Appendix and Colorectum.

Carr NJ, Emory TS, Sobin LH.

Department of Cellular Pathology, Southampton University Hospitals National Health Service Trust, Southampton, Hampshire, England (Dr Carr), and Department of Hepatic and Gastrointestinal Pathology, Armed Forces Institute of Pathology, Washington, DC (Drs Emory and Sobin).

Arch Pathol Lab Med 2002 Jul;126(7):837-841 Abstract quote

Context.-Carcinomas of the appendix are usually well-differentiated mucinous adenocarcinomas that tend to produce pseudomyxoma peritonei and do not show metastatic spread until late in the disease process. In contrast, adenocarcinomas of the colon and rectum rarely result in pseudomyxoma peritonei and frequently metastasize, even if mucinous and well differentiated. These differences in behavior may be reflected by differences at the molecular level.

Objectives.-To examine adenocarcinomas and their precursor lesions (adenomas) of the appendix and colorectum and to determine whether differences exist in the numbers of proliferating and apoptotic cells or in expression of p53, bcl-2, and the standard form of CD44 (CD44s).

Design.-Retrospective analysis of surgical specimens.

Setting.-Multicenter study.

Patients.-Individuals treated surgically for tumors of the appendix or colorectum.

Interventions.-Sections were cut from formalin-fixed surgical specimens and immunohistochemical tests were performed for Ki-67 (as a marker of proliferating cells), M30 (as a marker of apoptotic cells), p53, CD44s, and bcl-2. Main Outcome Measures.-Expression of Ki-67, M30, p53, CD44s, and bcl-2 in tumor cells. Results.-The appendiceal adenomas showed significantly lower Ki-67 counts, p53 expression, and bcl-2 expression. When compared with adenocarcinomas of the colorectum in general (mucinous and nonmucinous), the appendiceal adenocarcinomas showed significantly lower Ki-67 counts, M30 counts, and CD44s expression. However, when the analysis was confined to well-differentiated mucinous adenocarcinomas, only the M30 count was significantly different.

Conclusions.-The lower proliferative and apoptotic activity of appendiceal carcinomas and the lower CD44s expression are in keeping with their more indolent behavior compared with adenocarcinomas of the colorectum. However, when only the subset of well-differentiated mucinous adenocarcinomas was compared, only the apoptotic activity was different, suggesting that the other differences were related to the morphologic structure of the lesions.

CHROMOSOMAL ABNORMALITIES  


Mucinous and nonmucinous appendiceal adenocarcinomas: different clinicopathological features but similar genetic alterations.

Kabbani W, Houlihan PS, Luthra R, Hamilton SR, Rashid A.

Department of Pathology, University of Texas M. D. Anderson Cancer Center, Houston, Texas.

 

Mod Pathol 2002 Jun;15(6):599-605 Abstract quote

The genetic alterations of appendiceal carcinomas have not been reported in detail.

We studied the clinicopathological factors and genetic alterations including microsatellite instability, p53 overexpression, and mutations of the K-ras proto-oncogene of 30 appendiceal adenocarcinomas, consisting of 23 mucinous and 7 nonmucinous carcinomas. Sixteen (70%) mucinous carcinomas presented with pseudomyxoma peritonei, but 6 of 7 (86%) nonmucinous carcinomas presented with appendicitis (P =.002). All carcinomas were microsatellite stable, and p53 overexpression was present in only 1 of 30 (3%) carcinomas. K-ras mutation was present in 11 of 20 (55%) carcinomas, including 8 of 16 (50%) mucinous and 3 of 4 (75%) nonmucinous carcinomas. The mean survival of patients with mucinous carcinomas was 26 +/- 19 months compared with 13 +/- 9 months for patients with nonmucinous carcinomas (P =.0002).

Our findings suggest that mucinous and nonmucinous carcinomas of appendix have similar genetic alterations, but different clinical presentation and prognosis.

MISMATCH REPAIR GENE MUTATIONS  
Defective mismatch repair in the pathogenesis of low-grade appendiceal mucinous neoplasms and adenocarcinomas.

Misdraji J, Burgart LJ, Lauwers GY.

1James Homer Wright Pathology Laboratories at the Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Mod Pathol. 2004 Dec;17(12):1447-54. Abstract quote  

Defective DNA mismatch repair has been proposed as a second pathway for colonic carcinogenesis, particularly in tumors arising in the right colon.

We investigated whether tumors arising in the appendix are associated with defective DNA mismatch repair using immunohistochemistry for mismatch repair enzymes hMLH-1, hMSH-2, hMSH-6, and hPMS-2. These immunoassays have been shown to be highly sensitive and specific for defective DNA mismatch repair in sporadic and familial adenocarcinomas. Sporadic adenocarcinomas with defective DNA mismatch repair essentially always show loss of hMLH-1, while loss of hMSH-2, hMSH-6, or hPMS-2 is almost always due to germline mutation. In all, 35 cases of appendiceal epithelial neoplasms were evaluated, comprising 18 low-grade appendiceal mucinous neoplasms confined to the appendix; eight low-grade appendiceal mucinous neoplasms with extra-appendiceal spread (five peritoneum and ovaries, two peritoneum, one ovaries only); and nine invasive adenocarcinomas (three with metastatic disease).

All immunohistochemical slides were reviewed by two pathologists. One (11%) invasive adenocarcinoma showed absent expression of hMSH-2 and hMSH-6, but preserved hMLH-1 and hPMS-2 expression. This case was a 26-year-old female with a history of synovial sarcoma who presented with acute appendicitis and appendiceal perforation (median age for other invasive carcinomas, 62 years; range 38-76 years). The appendiceal tumor was a moderately differentiated, colonic-type adenocarcinoma without significant extracellular mucin or tumor-infiltrating lymphocytes. The remaining invasive carcinomas and low-grade appendiceal mucinous neoplasms demonstrated preserved expression of all mismatch repair enzymes, including the seven cases in which extra-appendiceal tumor was also evaluated.

We conclude that defective DNA mismatch repair does not play a role in the pathogenesis of low-grade appendiceal mucinous neoplasms. Defective DNA mismatch was found in 11% of invasive carcinomas, likely due to a germline mutation. These findings suggest that sporadic appendiceal neoplasia rarely arises through the defective DNA mismatch repair (mutator) pathway.

GROSS APPEARANCE/
CLINICAL VARIANTS
CHARACTERIZATION
GENERAL  


Primary epithelial tumors of the appendix and a reappraisal of the appendiceal "mucocele".

Aranha GV, Reyes CV.

Dis Colon Rectum 1979 Oct;22(7):472-6 Abstract quote

A 28-year review of the records at Hines V.A. Medical Center revealed 17 primary epithelial tumors of the appendix. Five of these tumors were benign and 12 malignant. It is suggested that the term mucocele be abandoned, because it represents the end result rather than a definite pathologic entity.

The majority of benign tumors and carcinoid tumors of the appendix are discovered incidentally to other procedures. The majority of adenocarcinomas cause symptoms and signs of appendicitis. Simple appendectomy is sufficient treatment of all benign tumors of the appendix, and for all carcinoids that show no gross local metastases and are less than 2 cm in diameter. Simple appendectomy followed by right hemicolectomy or initial right hemicolectomy is the treatment of choice for all carcinoids of the appendix that show gross local metastases and are 2 cm or more in diameter and for all adenocarcinomas of the appendix, whether mucinous or colonic, in the absence of distant metastasis.

A new classification for primary epithelial tumors of the appendix is suggested.


Primary appendiceal adenocarcinoma.

Ozakyol AH, Saricam T, Kabukcuoglu S, Caga T, Erenoglu E.

Division of Gastroenterology, School of Medicine, Osmangazi University, Eskisehir, Turkey.

Am J Clin Oncol 1999 Oct;22(5):458-9 Abstract quote

Adenocarcinoma of the appendix is rarely encountered and is usually discovered at the pathology examination of the surgical specimen. Adenocarcinoma of the vermiform appendix is a rare neoplasm and constitutes <0.5% of all gastrointestinal neoplasms.

There is no symptom of appendiceal cancer, and it is very difficult to diagnose preoperatively. Most female patients are diagnosed as having a gynecologic disease. Second primary synchronous and metachronous neoplasms, especially in the gastrointestinal tract, are found in up to 35% of patients with appendix adenocarcinoma.

We report a case of adenocarcinoma in a 56-year-old woman misdiagnosed as having right ovarian carcinoma, and we review the literature.

VARIANTS  
OVARIAN METASTASIS  


The morphologic spectrum of ovarian metastases of appendiceal adenocarcinomas: a clinicopathologic and immunohistochemical analysis of tumors often misinterpreted as primary ovarian tumors or metastatic tumors from other gastrointestinal sites.

Ronnett BM, Kurman RJ, Shmookler BM, Sugarbaker PH, Young RH.

Department of Pathology, The Johns Hopkins School of Medicine, Baltimore, Maryland, USA

Am J Surg Pathol 1997 Oct;21(10):1144-55 Abstract quote

Twenty cases of ovarian metastases derived from appendiceal adenocarcinomas were analyzed.

The most common presentation was a pelvic mass. The appendiceal and ovarian tumors were diagnosed concurrently in 15 cases; in the remaining five, the ovarian tumors were diagnosed before the appendiceal tumor. The appendiceal adenocarcinomas demonstrated four morphologic patterns: 1) signet ring cell type, with or without glandular or goblet cell differentiation (14 cases); 2) mixed signet ring cell and intestinal type (two cases); 3) intestinal type (two cases); and 4) typical colorectal type (two cases).

The ovarian tumors were bilateral in 16 cases and were histologically similar to the associated appendiceal tumor in each case. Ovarian metastases that demonstrate signet ring cell, glandular, and goblet cell differentiation mimic metastases from gastric adenocarcinoma. Those that are derived from well-differentiated mucinous appendiceal adenocarcinomas mimic primary ovarian mucinous tumors and metastases from the pancreas and biliary tract. Metastases of appendiceal adenocarcinomas of colorectal type simulate both metastatic colorectal carcinoma and primary ovarian endometrioid carcinomas. The appendiceal and ovarian tumors were immunophenotypically identical in each case.

Approximately 50% of the appendiceal and ovarian tumors were positive for cytokeratin 7 (CK 7), and all were positive for cytokeratin 20 (CK 20). CK 20 positivity of the ovarian tumors is consistent with gastrointestinal origin; CK 7 positivity does not confirm ovarian origin, because appendiceal carcinomas are positive in 50% of cases. Metastatic appendiceal adenocarcinoma should be considered in the differential diagnosis of mucinous ovarian tumors with signet ring cell, goblet cell, or intestinal type differentiation, especially when these tumors are associated with extraovarian disease and are bilateral.

PEDIATRIC  

Adenocarcinoma of the appendix in a child.

Driver CP, Bowen J, Bruce J.

Department of Paediatric Surgery, Royal Manchester Children's Hospital, Pendlebury, England.

J Pediatr Surg 1998 Sep;33(9):1437-8 Abstract quote

Adenocarcinoma of the appendix is unusual at any age but occurs mostly in an elderly population.

The authors report a unique case presenting in a 10-year-old child and emphasize the importance of subjecting all resected specimens to histological examination.

 

HISTOLOGICAL TYPES CHARACTERIZATION
GENERAL  
ADENOCARCINOMA-SMALL CELL  
Primary Mixed Adenocarcinoma and Small Cell Carcinoma of the Appendix: A Clinicopathologic, Immunohistochemical, and Molecular Study of a Hitherto Unreported Tumor.

Rossi G, Bertolini F, Sartori G, Bigiani N, Cavazza A, Foroni M, Valli R, Rindi G, De Gaetani C, Luppi G.

*Department of Pathologic Anatomy and Legal Medicine, Section of Pathology and daggerDepartment of Oncology and Hematology, Section of Oncology, University of Modena and Reggio Emilia; double daggerOperative Unit of Pathology, Hospital S. Maria Nuova, Reggio Emilia; and section signDepartment of Pathology and Laboratory Medicine, University of Parma, Parma, Italy.

Am J Surg Pathol. 2004 Sep;28(9):1233-1239. Abstract quote  

Appendiceal carcinoids range from well-differentiated endocrine tumor to well-differentiated endocrine carcinoma, while poorly differentiated (small cell) carcinoma has not been described in this site.

We report herein a case of mixed intestinal-type adenocarcinoma associated with a small cell carcinoma arisen in a 35-year-old woman and clinically presenting as an appendiceal abscess. The resected tumor histologically appeared as a biphasic lesion composed of a nonmucinous adenocarcinoma closely juxtaposed with a poorly differentiated (small cell) endocrine carcinoma.

The subsequent right hemicolectomy was unremarkable, but one pericolic lymph node showed a metastatic deposit consisting of the adenocarcinoma only. The patient thus underwent a chemotherapeutic protocol for colorectal cancer, and she is alive and well at the 65-month follow-up. Immunohistochemically, the adenocarcinoma strongly stained for cytokeratin 20 and carcinoembryonic antigen, while the endocrine component displayed a dot-like positivity for pan-cytokeratins and chromogranin. Of note, both components did not stain with CDX2 and p53. At genotypic analysis by microsatellite instability, both components shared many microsatellite alterations as well as a normal p53 gene setup, although small cell carcinoma harbored additional alterations.

Clinical and molecular findings led us to consider this lesion as a clonal tumor in which the endocrine component seems to derive from a progressive differentiation of the adenocarcinoma following a glandular-to-endocrine sequence.
MUCINOUS  
Appendiceal mucinous tumors and pseudomyxoma peritonei: histologic features, diagnostic problems, and proposed classification.

Pai RK, Longacre TA.

From the Department of Pathology, Stanford University School of Medicine, Stanford, CA
Adv Anat Pathol. 2005 Nov;12(6):291-311. Abstract quote  

Pseudomyxoma peritonei is an overused and underspecified condition that has garnered much attention in the historic literature. In recent years, this condition has been convincingly linked to appendiceal mucinous neoplasms, yet there has been insufficient attention to the histologic characteristics, classification, and differential diagnostic considerations of these neoplasms when encountered by the surgical pathologist.

This review provides a coherent approach to the diagnosis and classification of appendiceal mucinous tumors and the peritoneal implants associated with the pseudomyxoma peritonei syndrome with emphasis on differential diagnostic considerations and recommendations for the final pathology report.


Appendiceal mucinous neoplasms: a clinicopathologic analysis of 107 cases.

Misdraji J, Yantiss RK, Graeme-Cook FM, Balis UJ, Young RH.

 

Am J Surg Pathol. 2003 Aug;27(8):1089-103. Abstract quote

The classification of appendiceal mucinous tumors is controversial and terminology used for them inconsistent, particularly when they lack overtly malignant features but are associated with extra-appendiceal spread.

We reviewed 107 appendiceal mucinous neoplasms and classified them as low-grade appendiceal mucinous neoplasm (LAMN) (n = 88), mucinous adenocarcinomas (MACAs) (n = 16), or discordant (n = 3) based on architectural and cytologic features. LAMNs were characterized by a villous or flat proliferation of mucinous epithelium with low-grade atypia.

Thirty-nine tumors were confined to the appendix, but 49 had extra-appendiceal tumor spread, including 39 with peritoneal tumor characterized by mucin pools harboring low-grade mucinous epithelium, usually dissecting in a hyalinized stroma. Eight of the 16 MACAs lacked destructive invasion of the appendiceal wall and eight showed an infiltrative pattern of invasion. Extra-appendiceal tumor spread was present in 12 MACAs (four peritoneum, seven peritoneum and ovaries; one ovaries only). In MACAs with an infiltrative pattern, peritoneal tumor consisted of glands and single cells in a desmoplastic stroma. The peritoneal tumor in the remaining cases consisted of mucin pools that contained mucinous epithelium with high-grade atypia and, in some cases, increased cellularity compared with that seen in peritoneal spread in cases of LAMN. Three cases were classified as discordant because the appendiceal tumors were LAMNs but the peritoneal tumors were high-grade.

Follow-up was available for 49 LAMNs, 15 MACAs, and 2 discordant cases. None of the patients with LAMNs confined to the appendix experienced recurrence (median follow-up 6 years). LAMNs with extra-appendiceal spread were associated with 3-, 5-, and 10-year survival rates of 100%, 86%, and 45%, respectively. Patients with MACA had 3- and 5-year survival rates of 90% and 44%, respectively (p = 0.04). The bulk of peritoneal disease correlated with prognosis among patients with MACA (p = 0.04) and, to a lesser degree, among patients with LAMNs (p = 0.07).

We conclude that: 1) appendiceal mucinous neoplasms can be classified as either low-grade mucinous neoplasms or mucinous adenocarcinoma based on architectural and cytologic features; 2) tumors that can be confidently placed in the low-grade group (which requires rigorous pathologic evaluation of the appendix) and are confined to the appendix are clinically benign in our experience to date; 3) low-grade tumors confined to the appendix are morphologically identical to those with extra-appendiceal spread (except for the usual identification of breach of the wall in the latter cases) and the same designation is appropriate for the appendiceal neoplasia in each situation; 4) the long-term outlook for patients with low-grade tumors and peritoneal spread is guarded with just over half dying of disease after 10 years; 5) appendiceal mucinous tumors with destructive invasion of the appendiceal wall, complex epithelial proliferations, or high-grade nuclear atypia generally pursue an aggressive clinical course and should be classified as mucinous adenocarcinomas; 6) peritoneal tumor can be classified as involvement by LAMN or MACA, and this distinction is of prognostic significance; 7) bulky peritoneal tumor worsens prognosis; and 8) LAMNs associated with high-grade peritoneal tumor behave as adenocarcinoma.

NON-MUCINOUS  

 

SPECIAL STAINS/
IMMUNOPEROXIDASE
 
Immunohistochemical expressions of cytokeratins, mucin core proteins, p53, and neuroendocrine cell markers in epithelial neoplasm of appendix.

Yajima N, Wada R, Yamagishi S, Mizukami H, Itabashi C, Yagihashi S.

Department of Pathology (I), Hirosaki University School of Medicine, Hirosaki 036-8562, Japan.

Hum Pathol. 2005 Nov;36(11):1217-25. Abstract quote  

Epithelial neoplasms of appendix are infrequent, and their pathological features are not fully characterized. We collected 33 cases of appendiceal tumors and examined immunohistochemically the expression of cytokeratins (CK, CK7, and CK20), mucin core protein (MUC1, MUC2, MUC5AC, and MUC6), E-cadherin, chromogranin A, and p53 protein.

Gene analysis of TP53 was also conducted on exons 5 to 8. Clinically, mucinous tumors were predominant in females. Immunohistochemically, all the tumors expressed CK20, whereas CK7 was positive in one third of the cases. Similarly, MUC2 was expressed in all the tumors, whereas MUC1 and MUC5AC were detected in about a half of the cases. Although chromogranin A-positive cells are generally sparse in normal appendix, they were more common in mucinous tumors than in nonmucinous tumors. Contrary to the previous data reported (Mod Pathol 2002;15:599-605), mucinous carcinoma exhibited a higher frequency of p53-positive cells (mean 29%) compared with mucinous adenoma (2.8%) (P < .001), whereas nonmucinous tumors showed high levels of p53-positive cells to similar extent (51%-67%) in both adenoma and carcinoma. The high expression of p53 protein coincided with the presence of mutations in multiple sites of TP53 gene in mucinous tumors.

This is the first report that characterized the immunophenotypic profile of appendiceal epithelial neoplasms with an emphasis of a higher frequency of p53 positivity in mucinous carcinoma cases compared with mucinous adenoma in the appendix.
Mixed carcinoid and adenocarcinoma of the appendix: report of 4 cases with immunohistochemical studies and a review of the literature.

Lin BT, Gown AM.

Division of Surgical Pathology, Encino Tarzana Regional Medical Center, 18321 Clark Street, Tarzana, CA 91356, USA.
Appl Immunohistochem Mol Morphol. 2004 Sep;12(3):271-6. Abstract quote  

Four cases of mixed carcinoid and adenocarcinoma of the appendix were reported. All cases presented with a dominant cecal-appendiceal tumor mass and local metastasis. Two patients had multiple peritoneal implants mimicking primary peritoneal serous adenocarcinoma or carcinomatosis.

Histopathologic features of the tumors are similar, with infiltrating microglandular and cribriform patterns of tumor nests, and variable numbers of goblet cells. A literature review of "goblet cell carcinoid" that included nonlocalized cases revealed a significant percentage (>14%) of tumor-associated death, in contrast to the classic carcinoid tumor. Immunohistochemical stains were helpful to separate these tumors from carcinoid tumors and primary peritoneal serous adenocarcinoma. Mixed carcinoid and adenocarcinomas were cytokeratin (CK)-20 positive, and negative or weakly positive for chromogranin A and synaptophysin.

Carcinoid tumors were CK20 negative and diffusely positive for chromogranin A and synaptophysin. Peritoneal serous adenocarcinomas were CK20 negative. These cases were clinically aggressive, and 1 patient had multiple recurrences and responded partially to chemotherapy.

 

DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES
ADENOCARCINOID  


Adenocarcinoid (mucinous carcinoid) of the appendix.

Edmonds P, Merino MJ, LiVolsi VA, Duray PH.

Gastroenterology 1984 Feb;86(2):302-9 Abstract quote

Carcinoid tumors of the appendix are common incidental findings, but appendiceal tumors with histologic features of both carcinoids and adenocarcinomas are rare, and their biologic behavior is still unclear.

We studied 10 such cases among 45 appendiceal tumors seen at Yale-New Haven Hospital between 1960 and 1982. The patients, ranging in age from 23 to 65 yr, were all clinically symptomatic [acute appendicitis (5); abdominal mass (5)]. Right colectomy was performed in 5 patients; the other 5 underwent appendectomy only. In 1 case, metastasis to a lymph node was detected; 2 patients had ovarian metastases, and 4 patients had cecal invasion. One of the 10 patients died of widely disseminated tumor, 2 are living with persistent disease, and 5 remained free of disease from 1 to 5 yr after initial surgery. Two cases were lost to follow-up.

We conclude that the histology of these lesions is distinctive, enabling their differentiation from ordinary carcinoids. Because these lesions behave in a clinically more aggressive fashion than the usual appendiceal carcinoids, but are less virulent than adenocarcinoma, we support their classification as adenocarcinoids.

GOBLET CELL CARCINOID  


Goblet cell carcinoid tumor of the appendix. Report of five cases and review of the literature.

Chen V, Qizilbash AH.

Arch Pathol Lab Med 1979 Apr;103(4):180-2 Abstract quote

Five cases of goblet cell carcinoid tumor of the appendix showed characteristic histologic features that justified classification of these lesions as mucinous variants of carcinoid tumor. The tumor has low-grade malignancy, and metastases are uncommon.

Resemblance to mucinous adenocarcinoma of the appendix is striking, and the features that help to differentiate the two lesions are delineated.

METASTATIC ADENOCARCINOMA  

Acute appendicitis secondary to metastatic bronchogenic adenocarcinoma.

Gopez EV, Mourelatos Z, Rosato EF, Livolsi VA.

Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia 19104, USA.

Am Surg 1997 Sep;63(9):778-80 Abstract quote

Metastatic tumors to the appendix are not common. However, these tumors should be one of the differential diagnoses in patients with known primary malignancy, who present with signs and symptoms of acute appendicitis.

We report a case of an elderly male with poorly differentiated bronchogenic adenocarcinoma which metastasized to the appendix.

 

PROGNOSIS AND TREATMENT CHARACTERIZATION
PROGNOSTIC FACTORS  
GENERAL  
Does Mesoappendix Infiltration Predict a Worse Prognosis in Incidental Neuroendocrine Tumors of the Appendix? A Clinicopathologic and Immunohistochemical Study of 15 Cases

Giulio Rossi, MD, Riccardo Valli, MD, Federica Bertolini, MD, Pamela Sighinolfi, MD, Luisa Losi, MD, Alberto Cavazza, MD, Francesco Rivasi, MD, and Gabriele Luppi, MD
Am J Clin Pathol 2003;120:706-711 Abstract quote

We conducted a retrospective clinicopathologic and immunohistochemical study of the biologic significance of mesoappendix infiltration in 15 appendiceal neuroendocrine tumors selected from a series of 42 primary tumors. In all cases, the tumor was found incidentally and measured less than 2 cm (mean, 0.84 cm). In 13 cases, it was located in the tip of the appendix and in the midportion in 2.

Histologically, none showed relationship with overlying mucosa. Necrosis was absent; mitotic figures were rare. The Ki-67 labeling index was low (1%-2%). In all cases, S-100 protein immunostaining disclosed positive elements with cytoplasmic dendritic processes closely intermingled with neuroendocrine neoplastic cells. All patients (8 males; 7 females; mean age, 38.2 years) underwent simple appendectomy. A right-sided hemicolectomy was performed subsequently in 1 case. After a mean follow-up of 52.6 months (range, 8-143 months), none had died of disease or had recurrent or metastatic disease.

Our results confirm that appendiceal neuroendocrine tumors seem to have a different phenotype from those occurring in other gastrointestinal sites. Tumors less than 2 cm, even with mesoappendiceal infiltration, have an excellent prognosis, and simple appendectomy seems to be the appropriate therapeutic approach.


Primary adenocarcinoma of the appendix.

Delgado RR Jr, Mullen JT, Ehrlich FE.

South Med J 1975 Aug;68(8):976-8 Abstract quote

A case of primary adenocarcinoma of the appendix in which the patient had the usual symptoms of acute appendicitis is presented. A review of the literature showed the potential for early extension and nodal metastasis in this lesion and led to the recommendation of right hemicolectomy as the treatment of choice.

The operation should be done either primarily or secondarily after an appendectomy and should lead to a five-year survival of approximately 45%. Every effort should be made to make the diagnosis and provide definitive treatment at the primary operation by examining the appendix grossly and obtaining frozen section microscopic study of any suspicious tumor or ulceration.


Adenocarcinoma of the appendix: a clinicopathologic study.

Didolkar MS, Fanous N.

Dis Colon Rectum 1977 Mar;20(2):130-4 Abstract quote

Clinicopathologic correlation and survival were evaluated in 11 patients with adenocarcinomas of the appendix. This extremely rare tumor was seen most often in patients in the fifth decade of life. Acute appendicitis was the most common mode of presentation (8/11). A few patients (3/11) showed signs of distant metastases from an occult primary tumor in the appendix.


Primary malignant neoplasms of the appendix.

McCusker ME, Cote TR, Clegg LX, Sobin LH.

Department of Epidemiology and Preventive Medicine, University of Maryland, Baltimore, Maryland.

Cancer 2002 Jun 15;94(12):3307-12 Abstract quote

BACKGROUND
Cancer of the appendix is an uncommon disease that is rarely suspected rarely before surgery. Although several case series of these tumors have been published, little research has been anchored in population-based data on cancer of the appendix.

METHODS
This analysis included all actively followed cases of appendiceal neoplasms reported to the National Cancer Institute's Surveillance, Epidemiology and End-Results (SEER) program between 1973 and 1998. Tumors were classified as "colonic type" adenocarcinoma, mucinous adenocarcinoma, signet ring cell carcinoma, goblet cell carcinoid, and "malignant carcinoid" (SEER only collects data on carcinoids specifically classified as malignant). We compared incidence, overall survival and survival rates by extent of disease at diagnosis.

RESULTS
Between 1973 and 1998, 2117 appendiceal malignancies were reported to the SEER program, of which 1645 cases were included in the analysis. Age-adjusted incidence of cancer of the appendix was 0.12 cases per 1,000,000 people per year. Demographic characteristics of patients with goblet cell carcinoid tumors were midway between those of patients with malignant carcinoid and all types of adenocarcinomas. After controlling for age and extent of disease at diagnosis, the overall survival rate for patients diagnosed between 1983 and 1997 (n = 1061) was significantly worse for those with signet ring cell carcinoma than for those with any other tumor type (P < 0.01). In addition, overall survival rates were better for patients with malignant carcinoid (P = 0.01).

CONCLUSIONS
Demographic characteristics of patients with cancer of the appendix vary by histology. Except for signet ring cell carcinoma and malignant carcinoid, the extent of disease at time of diagnosis is a more important predictor of survival than histology.

TREATMENT  
SURGERY  
Appendiceal neoplasms with peritoneal dissemination: outcomes after cytoreductive surgery and intraperitoneal hyperthermic chemotherapy.

Stewart JH 4th, Shen P, Russell GB, Bradley RF, Hundley JC, Loggie BL, Geisinger KR, Levine EA.

Department of General Surgery, Surgical Oncology Service, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina, 27157,
Ann Surg Oncol. 2006 May;13(5):624-34. Epub 2006 Mar 14. Abstract quote  

BACKGROUND: Appendiceal neoplasms frequently present with peritoneal dissemination (PD) and have a clinical course marked by bowel obstruction and subsequent death. Few data have correlated outcome with appendiceal histology after cytoreductive surgery and intraperitoneal hyperthermic chemotherapy (IPHC). We have reviewed our experience with cytoreductive surgery and IPHC for PD from the appendix.

METHODS: A total of 110 cases of PD from proven appendiceal neoplasms treated with IPHC were identified from a prospectively managed database. Tumor samples were classified on pathologic review as disseminated peritoneal adenomucinosis (n = 55), peritoneal mucinous carcinomatosis (PMCA) with intermediate features (n = 18), PMCA (n = 29), or high-grade nonmucinous lesions (n = 8). A retrospective review was performed with long-term survival as the primary outcome measure.

RESULTS: A total of 116 IPHCs were performed on 110 patients for appendiceal PD between 1993 and 2004. The 1-, 3-, and 5-year survival rates for all cases were 79.9% +/- 4.1%, 59.0% +/- 5.7%, and 53.4% +/- 6.5%, respectively. When stratified by histology, disseminated peritoneal adenomucinosis and intermediate tumors had better 3-year survival rates (77% +/- 7% and 81% +/- 10%) than PMCA and high-grade nonmucinous lesions (35% +/- 10% and 15% +/- 14%; P = .0032 for test of differences between groups). Age at presentation (P = .0134), performance status (P < .0001), time between diagnosis and IPHC (P = .0011), resection status (P = .0044), and length of hyperthermic chemoperfusion (P = .0193) were independently associated with survival.

CONCLUSIONS: The data show that long-term survival is anticipated in most patients who are treated with cytoreduction and IPHC for appendiceal PD. The findings presented herein underscore the important prognostic characteristics that predict outcome after IPHC in patients with PD. In all, this work establishes a framework for the consideration of IPHC in future trials for appendiceal PD.


Adenocarcinoma of the vermiform appendix: retrospective study and literature review.

Panton ON, Bell GA, Owen DA.

Can J Surg 1983 May;26(3):276-9 Abstract quote

Adenocarcinoma of the vermiform appendix is a rare clinical entity, fewer than 200 cases having been reported.

The authors carried out a retrospective review over a 25-year period and found five patients admitted to the Vancouver General Hospital with primary appendiceal adenocarcinoma. Four other patients, initially reported as having appendiceal adenocarcinoma, were found after critical microscopic review to have had either benign disease or mucinous carcinoid. Primary epithelial neoplasms of the appendix demonstrate a wide variety of histologic types and because of the different clinical behaviour, an accurate diagnosis must be made.

For the benign tumours, appendectomy alone will suffice but for adenocarcinoma of the appendix, right hemicolectomy is recommended.


Adenocarcinoma of the appendix.

Ferro M, Anthony PP.

Dis Colon Rectum 1985 Jun;28(6):457-9 Abstract quote

Three cases of adenocarcinoma of the appendix are reported. All three patients presented with acute appendicitis and the tumors were diagnosed only on histologic examination of the excised appendix.

The first patient subsequently had a right hemicolectomy and was proven to have a Dukes' B tumor. The second patient probably had a Dukes' B also, but no further surgery was performed because of advanced presenile dementia. Advanced disease was found in the third patient. Analysis of 145 cases reported over the last ten years suggests that, unless the tumor is in Dukes' A stage, right hemicolectomy should be carried out if the patient is fit for radical surgery.

The overall prognosis appears to be the same as that for carcinoma of the colon.


Adenocarcinoma of the vermiform appendix.

Harris GJ, Urdaneta LF, Mitros FA.

Department of Surgery, University of Iowa, College of Medicine, Iowa City.

J Surg Oncol 1990 Aug;44(4):218-24 Abstract quote

Primary adenocarcinoma of the appendix is rare. Eleven patients with this rare neoplasm have been evaluated at our institution over a 50-year period.

We have reviewed the presentation and clinical course of these patients, and have compared them with those described in the literature. The presenting signs and symptoms, physical findings, and treatment were similar to those described in the literature. However, the 5-year survival of 20% is lower than most series, and reflects the advanced stage of disease at the time of diagnosis in this group of patients.

Despite the low 5-year survival, we feel that aggressive therapy (right hemicolectomy) is necessary to obtain long-term survival.

 

The natural history of surgically treated primary adenocarcinoma of the appendix.

Nitecki SS, Wolff BG, Schlinkert R, Sarr MG.

Department of Surgery, Mayo Clinic, Rochester, Minnesota.

Ann Surg 1994 Jan;219(1):51-7 Abstract quote

OBJECTIVE: The aim of this investigation was to determine the prognostic variables and optimal surgical procedure for patients with adenocarcinoma of the appendix.

SUMMARY BACKGROUND DATA: Primary adenocarcinoma of the appendix is a rare malignancy that constitutes less than 0.5% of all gastrointestinal neoplasms. However, the prognostic factors and the preferred surgical procedure and outcome are poorly understood.

METHODS: The authors reviewed their institutional experience from 1976 to 1992 in treating 94 consecutive patients with primary adenocarcinoma of the appendix. Patients with carcinoid tumors or those in whom the diagnosis of primary cecal cancer could not be ruled out were excluded from the study.

RESULTS: Fifty-two (55%) patients had the mucinous variety, of which 22 had pseudomyxoma peritonei; the other 45% had the colonic and adenocarcinoid types of tumor. The most common presentation was that of acute appendicitis. Interestingly, in no patients was the correct diagnosis made before surgery, and it was entertained intraoperatively in only 30 patients (32%). The cure 5-year survival rate was 55%, but it varied with stage (A, 100%; B, 67%; C, 50%; and D, 6%; p < 0.01) and with grade (I, 68%, and III, 7%; p < 0.01). Patients with the mucinous type had a better prognosis than those with the colonic type (p < 0.01). The survival rate was superior after right hemicolectomy versus appendectomy alone (68% vs. 20%, p < 0.001). Right hemicolectomy performed as a secondary procedure resulted in the upstaging of 38% of the patients' tumors. A second primary malignancy occurred in 33 patients (35%), of which 17 were located in the gastrointestinal tract.

CONCLUSIONS: Primary adenocarcinoma of the appendix should be treated by right hemicolectomy, even if it is a secondary procedure. Surveillance for synchronous or metachronous tumors, especially in the gastrointestinal tract, is warranted.

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