INTRODUCTION
Acute appendicitis is one of the most common surgical emergencies in the world, and appendectomy is a routine procedure in general surgery.(1,2) Acute appendicitis occurs frequently in the second and third decades of life. Males have a lifetime probability of 8.6% compared with 6.7% in females.(3) The occlusion of the appendix lumen by a faecolith or lymphoid hyperplasia is the most common pathogenesis. However, surgical literature reports that rare causes have been diagnosed on histopathology. These include viral infections (cytomegalovirus), parasites (schistosomiasis, enterobiasis, ascariasis) and mycobacterium species (tuberculosis). Endometriosis, inflammatory bowel disease (Crohn's) and neoplasms (carcinoid tumours, adenocarcinoma, and mucinous cystic neoplasms) may also lead to appendicitis.(2,4)
The literature on unusual histopathology of the appendix is scanty. Akbulut et al. reviewed 128 articles published between January 2000 and November 2010 and reported unusual histopathology in 1.7% (1366) of the 80,698 cases analysed.(2) The most common of these were Enterobius vermicularis (28.4%), followed by carcinoid tumour (21.9%) and schistosomiasis (12.7%). Very few studies of appendix histopathology have been reported in South Africa. Chamusa et al. analysed 324 histopathology reports from patients who underwent appendectomy at Prince Mshiyeni Memorial Hospital in Durban KwaZulu-Natal.(1) The reported incidence of unusual findings was 8.6%, with the most frequent finding as schistosomiasis (42.8 %).(1) In a recent study conducted by Jolayemi et al. at Grey's Hospital in Durban KwaZulu-Natal, 290 histopathological reports were reviewed, and the incidence of unusual histopathology was 5.9%. The most frequent unusual finding was parasites (5.8%), and the incidence of premalignant conditions was low at 0.7%.(5)
The current study was undertaken to determine the incidence of unusual and unsuspected appendix pathologies in patients who underwent appendectomy at three tertiary hospitals associated with the University of the Witwatersrand in Johannesburg, South Africa. Particular attention has been paid to those conditions involving the appendix that require additional investigation and management.
METHODS
A retrospective review was undertaken of histopathological reports of appendix specimens obtained during appendectomies performed between January 2012 and December 2014, in the three academic hospitals of Johannesburg (Chris Hani Baragwanath Academic Hospital, Charlotte Maxeke Johannesburg Academic Hospital and Helen Joseph Hospital). All specimens were examined by pathologists of the National Health Laboratory Services (NHLS). Parameters analysed included demographics of the patient as well as the histopathology report. Appendix specimens that were part of colonic resection for pathologies unrelated to the appendicitis were excluded from the study. The data was captured using Microsoft Excel, and the data was analysed using Stata 13 (Manufacturer = Statacorp, Stata LLC 4905 Lakeway Drive, College station, Texas 77845-4512. USA:1-800-782-8272, email: service@stata.com). Ethical approval for the study was obtained from the Human Research Ethics Committee (Medical) of the University of the Witwatersrand (M150259).
RESULTS
A total of 2408 histopathology results were obtained from the NHLS, 164 appendix specimen that was part of colonic resection for other pathologies were excluded from the study. Of the 2244 histopathology specimens, 8.8% were found to have a normal appendix, 52.7% were secondary to acute appendicitis, 30.1% were related to complicated appendicitis three per cent (3%) of patients had peritonitis unrelated to the appendix. Perforated, gangrenous or suppurative appendicitis were reported as a complicated case. Overall, the median (range) age was 25.6 years (11 months–88 years), and the gender distribution was 61.9 % male and 38.1% female.
Unusual histopathology reports represented 5.3% (119/2244) of cases and of these, some presented as acute appendicitis and others as complicated appendicitis. From Table 1, the most common causes of unusual pathologies were parasites (37%) led by schistosomiasis (24.3%), followed by neoplasm (20%) and fibrous obliteration (14.2%). The mean age of the patients with schistosomiasis was 27 years, of which 72.4% were male and 27.6% were female. The overall incidence of neoplasms was 1.06% (24/2244), and the most common neoplasm was carcinoid tumour (0.3%) (Table 2).
Aetiology of the unusual histopathology of the appendix
| Aetiology | Number (n = 119) | Percentage (%) | % of the total number (n = 2244) |
|---|---|---|---|
| Parasites: | 45 | 37 | 2.00 |
| Schistosomiasis | 29 | 24.3 | 0.89 |
| Enterobius vermicularis | 10 | 8.40 | 0.44 |
| Amoebiasis | 4 | 3.36 | 0.18 |
| Ascaris lumbricoides | 2 | 1.68 | 0.09 |
| Neoplasms | 24 | 20 | 1.06 |
| Fibrous obliteration/Neuroma | 17 | 14.20 | 0.75 |
| Mycobacterium tuberculosis | 9 | 7.50 | 0.40 |
| Granulomatous inflammation | 12 | 10 | 0.53 |
| Typhoid | 4 | 3.36 | 0.18 |
| Spirochaetosis | 3 | 2.50 | 0.13 |
| Neurogenous hyperplasia | 2 | 1.68 | 0.09 |
| Cryptococcus | 1 | 0.80 | 0.04 |
| Actinomycosis | 1 | 0.80 | 0.04 |
| Melanosis coli | 1 | 0.80 | 0.04 |
Subtype of the appendix neoplasm
| Subtypes | Number | % of the total number (n = 2244) |
|---|---|---|
| Benign neoplasms: | ||
| Mucocele (Mucinous cystadenoma) | 3 | 0.13 |
| Atypical leiomyoma | 3 | 0.13 |
| Malignant neoplasms: | ||
| Adenocarcinoma | 5 | 0.20 |
| Mucinous adenocarcinoma | 3 | 0.13 |
| Malignancy type unspecified | 1 | 0.04 |
| Unspecified neoplasms: | ||
| Lymphoma | 2 | 0.09 |
| Carcinoid tumours (neuroendocrine tumours) | 7 | 0.30 |
The median age of the patients with confirmed appendicitis was 25 years with a male:female ratio of 1.7:1 (64% vs. 36%). Of the patients with complicated appendicitis, 61.9% were male and 38.1% were female. The median age of the patients with normal appendix was 25 years and the gender distribution was 46.4% male and 53.5% female.
DISCUSSION
The literature reports that clinical and macroscopic assessment of the appendix during surgery is unreliable and therefore routine histopathology confirmation is advised.(6) Even those appendices that appear to be normal at operation may be the site of an underlying pathology which can be self-limiting, such as mesenteric lymphadenitis. In addition, the appendix can be involved in an inflammatory process originating from adjacent structures, for example, pelvic inflammatory disease and tuberculous peritonitis.(7) In these cases, the histopathology report is likely to be that of serositis without trans-mural inflammation. The primary pathological process can be overlooked during appendectomy especially when the operation is done through a limited incision.
In most cases, patients who are admitted with appendicitis recover within a few days after surgery and are discharged before histopathology examination of paraffin sections is completed by the NHLS. This suggests that patients with neoplastic or chronic infection may leave the hospital and can be lost to follow-up before further management is instituted. Therefore, it is mandatory to always check the histopathology report and to address any unexpected pathology at follow-up or even to contact the patient earlier to expedite the management.
In this study, which is the largest case series of histopathological assessments of appendix at surgery in South Africa, the rate of unusual histopathology of the appendix is reported as 5.3%. The latter is higher than the reported 1.7% from the retrospective analysis of 80,698 cases by Akbulut et al.(2) Our most common histopathological findings in the unusual pathology group were parasitic infections (37%) topped by schistosomiasis (24.3%), followed by neoplasms (20%), fibrous obliteration (14.2%), granulomatous inflammation (10%) and mycobacterium tuberculosis (7.5%). The other aetiologies (11.3%) included typhoid fever, spirochaetosis, neurogenous hyperplasia, cryptococcus, actinomycosis and melanosis coli. The above findings may be a reflection of increased burden of infectious disease in South Africa that include the human immunodeficiency virus (HIV) and high incidence of tuberculosis, as well as many other opportunistic infections.(8) Parasitic infections are endemic in many informal settlements in Africa and in South Africa, specifically, where 55.5% of inhabitants live below the poverty line and where lack of clean running water and adequate sanitation promote transmission of infections.(9)
Schistosomiasis merits a special mention. It is the third-most devastating tropical disease worldwide after malaria and intestinal helminthiasis and is a major source of morbidity and mortality.(10) Schistosomiasis infects more than 200 million individuals in the world (90% in Africa) and causes up to 200,000 deaths every year.(11,12) In South Africa, schistosomiasis infects an estimated 4 million people.(12) The endemic areas are Mpumalanga, KwaZulu-Natal, Limpopo and Eastern Cape.(12) Schistosomiasis is not endemic in the Gauteng province. The exodus of rural population to major metropolitan areas like Johannesburg may explain the higher incidence of schistosomiasis in our study. Schistosomiasis is important to recognise as it affects the urogenital system, the gastrointestinal tract (GIT) and can have disastrous complications such as portal hypertension. Prompt treatment with Praziquantel can avert this negative outcome.
Neoplasms of the appendix need to be recognised and treated appropriately to prevent a potentially curable disease from metastasis. For most malignant tumours of the appendix, an appendicectomy alone is not adequate and further work-up is required to determine the extent of locoregional invasion and the presence of distant metastasis.(13) Mucinous neoplasms can either be benign (cystadenoma) or malignant (cystadenocarcinoma). For lymphoma of the appendix, a patient will require chemotherapy in addition to the appendectomy.
Appendicitis is mostly an acute event and the development of a complication is related to the time from onset of symptoms to surgery.(1,14) Surgeons should maintain a low threshold for surgery to minimise the complication rate. It is our opinion that since the diagnosis of appendicitis is mainly clinical, time should not be wasted to request additional investigations if they will not significantly alter the management plan. In the female patient, the ultrasound may be of use to exclude gynaecological pathologies in case of diagnostic dilemma. However, it is also important to emphasise that ultrasound is operator dependant and one is not expected to always see the appendix since its most common location is retrocaecal (65%).(7) In our experience, the higher incidence (30.1%) of complicated appendicitis on histopathology in our study is likely caused by a delayed presentation and therefore delayed surgery. Histopathological examination of the appendix specimen is crucial to ascertain the diagnosis of appendicitis and to rule out the differential diagnosis.
CONCLUSION
In this case series of histopathology of the appendix, the largest in South Africa to date, unusual histopathologies represented 5.3% of the appendix specimens. Parasites, of which schistosomiasis was the leading cause, and neoplasms were the leading aetiologies. These unusual findings require specific treatment that can be instituted only if the histopathology reports are routinely checked post operatively. Therefore, it is important to send all appendix specimens for histopathology assessment and to follow up appropriately thereafter.