Appendiceal Specimens Research Articles

Appendicopathy—a clinical and diagnostic dilemma

The term "neurogenic appendicopathy" has been used for patients operated on for acute appendicitis with their appendices lacking signs of acute inflammation. The aim of this retrospective study was to clarify the presence of potential neurogenic appendicopathies, analyzing patients' clinical symptoms and their corresponding appendiceal specimens. One hundred twenty-one patients were identified showing a histological diagnosis of chronic appendicitis. Eventually, 40 patients qualified for the potential diagnosis "neurogenic appendicopathy." Appendix specimens were immunohistochemically examined for the expression of S-100, vasoactive intestinal polypeptide (VIP), and substance P. Controls consisted of 110 patients with acute appendicitis and 120 patients following appendectomies operated on for other reasons. Eventually, 40 of 120 patients qualified for the potential diagnosis "neurogenic appendicopathy." Compared to patients with acute appendicitis, there was only little difference in clinical symptoms. Histologically, neuromas, thought of being characteristic of neurogenic appendicopathy, were demonstrated significantly more often in the control group (p = 0.01). S-100 was significantly more expressed in the appendicopathy group (p = 0.0024), but nearly 50% of control specimens showed an intense staining, too. S-100(+) neurofibers were significantly (p = 0.00122) more often found in the mucosa of appendicopathy specimens, but this was true for only 25% of specimens. VIP was more strongly expressed in control specimens (p = 0.0211). Substance P was of no diagnostic value. Our study could not confirm the neurogenic origin of appendicopathies. Yet, clinical data strongly suggest the existence of the entity "appendicopathy." Therefore, we suggest removing a macroscopically unaffected appendix in patients with appendicitis-like symptoms if, on laparoscopy, no other cause can be found.

Neurogenic Appendicopathy: Clinical, Macroscopic, and Histopathological Presentation in Pediatric Patients

The proliferation of nerve fibers in the appendix, in association with an increase of the neuropeptides such as vasoactive intestinal peptide and substance P characterizes neurogenic appendicopathy (NA), which may mimic the symptoms of acute appendicitis (AA). It may be difficult to differentiate this little known distinct pathological entity clinically from AA. The aim of this study is to describe the epidemiology, clinical signs, and histological description of NA in pediatric patients. After institutional review board approval, all appendiceal specimens from children who underwent appendectomy between February 2006 and December 2008 were analyzed. Analysis included age, gender, clinical symptoms, blood tests, intraoperative macroscopic assessment of the appendix, and the histopathological type of NA. NA was diagnosed by hematoxylin-eosin staining and /or S-100 immunochemistry and then classified into different histopathological groups. Of the 385 appendix specimens examined, 29 (7.5%) met the histopathological criteria of NA. The median duration of abdominal pain was 2 days (range, 1 to 7). The surgeon characterized the appendix as follows: not inflamed in 5 (17.2%), acute in 17 (58.6%), phlegmonous in 4 (13.8%), and perforated in 3 patients (10.4%). Histopathological diagnosis of NA classified the specimen as axial neuroma in 2 (7%), mucosal in 12 (41%), and submucosal in 15 cases (52%). NA is a relatively common diagnosis in children. NA must be considered in patients with recurrent right lower quadrant pain or signs of AA, even if intraoperative findings are normal. For these patients, we recommend appendectomy and consideration of a subsequent histopathological workup.

Acute Appendicitis from Metastatic Small Cell Lung Cancer

A 62-year-old female presented to the emergency department (ED) with right lower quadrant pain for 3 days. Past medical history was notable for small cell lung cancer (SCLC) with brain metastases. A staging positron emission tomography (PET) performed 10 days prior to presentation showed fludeoxyglucose uptake in the proximal appendix without surrounding inflammation (Figure 1). Figure 1 Positron emission tomography performed 10 days prior to presentation showing fludeoxyglucose uptake in the proximal appendix without surrounding inflammation consistent with appendiceal metastasis (arrow). In the ED, her physical exam was notable only for right lower quadrant tenderness to palpation, without rebound or guarding. Vital signs were within normal limits. Laboratory results were notable for a white blood count of 22 K/uL with 94% neutrophils (<5% bands). Contrast-enhanced abdominal computed tomography (CT) was performed in the ED showing a dilated appendix with enhancing wall and surrounding fat stranding suggestive of acute appendicitis (Figure 2). She was taken to the operating room emergently for a laproscopic appendectomy, which revealed a perforated appendix. The patient did well and 1 week postoperatively resumed treatment for her SCLC. Figure 2 Contrast-enhanced abdominal computed tomography of the abdomen performed in the emergency department showing a dilated appendix with enhancing wall and surrounding fat stranding (arrow) suggestive of acute appendicitis. Pathology of the appendiceal specimen demonstrated oval cells and nuclear molding consistent with small cell carcinoma involving the musclaris propria. Malignancies are a rare but known cause of appendiceal obstruction and inflammation, most commonly primary tumors, such as carcinoid or adenocarcinoma. This case of appendicitis from metastatic SCLC is exceedingly more rare, with only 7 prior case reports documented.1,2 Interestingly, this patient also had a staging PET CT that detected the metastasis prior to appendiceal obstruction and symptom onset. Other case reports have described screening PET CT incidentally diagnosing acute appendicitis.3,4 While metastases are an uncommon cause of appendiceal obstruction and inflammation, they should be considered as part of the differential diagnosis when a patient with known malignancy presents with symptoms consistent with appendicitis.

Parasitosis in Appendectomy Cases

Aim: Obstruction of lumen of appendix vermiformis causes inflammation and requires surgery. The study aimed to detect any parasitosis in appendiceal specimens brought to pathology laboratory. Method: A total 916 appendectomy specimens from Faculty of Medicine at Inonu University between 2002 and 2005 were examined for inflammation and luminal parasitosis. Result: Adult worms and eggs of Enterobius vermicularis were detected in 23 (2.5%) of all cases, while Taenia spp. were found in only 2 (0.2%) cases. Also parasites were found in 8 of (2.0%) of 391 construction appendicitis, and in 5 (1.3%) of 384 acute appendicitis cases. Moreover, plasma cells and polymorphonuclear leukocytes were observed, respectively, in 18, and 2 of Appendix vermiformis cases with parasite. Eosinophils in lamina propria were detected in all cases. Conclusion: Therefore, the intestinal parasitosis should be considered in the differential diagnoses of appendicitis. Education on how to prevent parasitosis should be included in training programs to avoid any unnecessary surgery.

Intravascular lymphocytosis in acute appendicitis: potential mimicry of chronic lymphocytic leukaemia

Intravascular lymphocytosis (IVL) in appendectomy specimens is a fairly common phenomenon but has not been described and studied in detail. The aim was to describe the IVL phenomenon in appendiceal specimens removed for appendicitis that can mimic chronic lymphocytic leukaemia and to investigate factors that could contribute to the development of IVL. The clinicopathology of 100 appendectomy cases and the appendices from 20 right hemicolectomy cases were reviewed. The IVL phenomenon was more commonly seen in laparoscopic appendectomy specimens [Fisher's exact 0.011, odds ratio (OR) 3.14] and in patients <38 years old (Fisher's exact 0.012, OR 3.01). Surgical manipulation and the patient's innate immunity are contributary factors to the development of the IVL phenomenon. Pathologists should be aware of this histological artefact in order to prevent overdiagnosis of intravascular lymphoid neoplasia.

A Yo-Yo Appendiceal Tubular Adenomatous Polyp - Now What Do We Do?

Purpose: 52 year old homeless African American male with no known GI history presents with acute on chronic anemia. He was admitted for dizziness and found to have a drop in his baseline hemoglobin from 10 gm/dl to 3 gm/dl. He did not describe overt bleeding. On physical examination he had conjunctival pallor and a flow murmur. An EGD and colonoscopy was performed. On colonoscopy, upon intubation of the cecum, the appendiceal orifice initially appeared normal (Figure 1). However, just prior to withdrawal from the cecum, a polyp with honeycombed capillary appearance protruding from the appendiceal orifice was discovered (Figure 2). The cecum was reintubated and the appendiceal orifice again appeared normal. The cecum was desufflated and the appendiceal orifice was manipulated and suctioned. A long pedunculated appearing polyp was seen protruding in and out of the appendiceal orifice like a yo-yo. It was extracted with biopsy forceps (Figure 3). The polyp was not resected as we were unable to gauge the extent of the polyp within the appendiceal orifice. Biopsies were taken and were consistent with a tubular adenoma. The patient is being evaluated for surgical resection. Tubular adenomatous polyps of the appendix are exceedingly rare, found in 0.02% of appendiceal specimens on post surgical resection and in 0.01% postmortem in one autopsy study. (1,2,3) The identification of appendiceal polyps endoscopically is even more uncommon. Appendiceal polyps are usually asymptomatic, however, if they become significantly enlarged they can cause intussusception. (4) Radiographic studies may aide in detection of appendiceal polyps if colonoscopy is at first negative. However, colonoscopy is the preferred first choice as it also provides the opportunity to acquire tissue for diagnosis. There is concern that appendiceal tubular adenomas may progress to adenocarcinoma as in the colon. There is an association between appendiceal tubular adenomatous polyps and colon cancer, up to 20% in two different studies. (5,6) Management has varied from endoscopic resection to surgical resection. Endoscopic resection must be taken carefully as some appendiceal polyps may masquerade as a prolapsed appendix. A few case reports suggest that surgical resection might be a better approach. (1) Previous endoscopic treatment was later found to have residual tubular adenoma still present in the appendix after appendectomy. (1) In conclusion, appendiceal polyps must be examined carefully with emphasis on surgical resection. Care must be taken to examine the colon thoroughly, as up to 20% of patients with appendiceal tubular adenomas also have colon cancer.

1236: High-Resolution Ultrasonography(US) of Appendiceal Specimens: Differentiation of Acute Non-Perforated Appendicitis from Perforated Appendicitis

To analyze surgical specimens from patients with acute non-perforated and perforated appendicitis using high-resolution ultrasonography (US), and to correlate the US features with the pathologic findings. One hundred and six surgical appendix specimens obtained from patients with suspected acute appendicitis were evaluated. The following US features were evaluated for differentiating acute non-perforated appendicitis from perforated appendicitis: circumferential loss of the echogenic submucosal layer, disruption of the serosal layer, asymmetrical wall thickening, the sum of opposing walls ≥ 9 mm and the presence of appendicoliths. The sensitivity and specificity of the US findings for diagnosing perforated appendicitis were determined. All US features were detected significantly more often in the perforated appendicitis group of specimens. The disruption of the serosal layer was the most significant independent predictor of perforation (p < .001). The sensitivity for circumferential loss of the echogenic submucosal layer, disruption of the serosal layer, asymmetrical wall thickening, wall thickness ≥ 9 mm, and the presence of appendicoliths individually was 84.6%, 69.2%, 61.5%, 73.1% and 46.2%, respectively. The specificity for all of these findings was 86.3%, 98.7%, 95.0%, 85.0% and 85.0%, respectively. High-resolution US of appendiceal specimens was very useful for differentiating acute non-perforated from perforated appendicitis.

Rare Cystic Mucinous Cystadenoma Presenting as a Scrotal Mass

Recently, our institution reported on a rare primary retroperitoneal mucinous cystadenocarcinoma which was only the second type of this kind of tumor ever reported in a male patient. To our knowledge, we report the first male case of a primary mucinous cystadenoma presenting as an enlarging scrotal mass. These lesions are extremely rare and represent only 0.3% of all appendiceal specimens. Because the number of these tumors remains limited, proven treatment regimens and the necessary follow-up have yet to be elucidated. We hope to provide further insight in the monitoring and treatment of these tumors.

Appendiceal neoplasms and pseudomyxoma peritonei: A population based study

Background Pseudomyxoma peritonei (PMP) is a rare disease with an estimated incidence of 1 per million per year, and is thought to originate usually from an appendiceal mucinous epithelial neoplasm. However it is not known exactly how often these neoplasms lead to PMP. The aim of this study is to investigate the incidence of both lesions and their relation. Methods The nationwide pathology database of the Netherlands (PALGA) was searched for the incidence of all appendectomies, the incidence of primary epithelial appendiceal lesions and the incidence and pathology history of patients with PMP. All regarded the 10-year period of 1995–2005. Results In the 10-year period 167,744 appendectomies were performed in the Netherlands. An appendiceal lesion was found in 1482 appendiceal specimens (0.9%). Nine percent of these patients developed PMP. Coincidentally, an additional epithelial colonic neoplasm was found in 13% of patients with an appendiceal epithelial lesion. A mucinous epithelial neoplasm was identified in 0.3% (73% benign, 27% malignant) of appendiceal specimens and 20% of these patients developed PMP. For mucocele and non-mucinous neoplasm the association with PMP was only 2% and 3%, respectively. From the nationwide database 267 patients (62 men and 205 women) with PMP were identified, which demonstrates an incidence of PMP in the Netherlands approaching 2 per million per year. The primary site was identified in 68% and dominated by the appendix (82%). Conclusions Primary epithelial lesions of the appendix are rare. One third of these lesions are mucinous epithelial neoplasms and especially these tumours may progress into PMP. The incidence of PMP seems to be higher than thought before. Furthermore there is a considerable risk of an additional colonic epithelial neoplasm in patients with an epithelial neoplasm at appendectomy.

Primary Carcinoma of the Appendix – Hull Series

Background: Appendiceal carcinoma (AC) is a rare entity that does not have a well-defined treatment strategy. At presentation, most patients are clinically thought to have appendicitis and the diagnosis is made only by formal histology. Once the diagnosis of AC is made, patients are treated by various strategies including surgery, chemotherapy depending on nodal status of the disease. Aim: To review the Hull hospitals’ experience with AC. Methods: Between 1982 and 2002, 10 patients with primary AC were seen. The histopathology reports of all appendiceal specimens removed were traced. Follow-up was by chart review or patient follow-up as appropriate. We did not include patients with primary carcinoid tumours or secondary adenocarcinoma. Results: There was an equal sex distribution. All patients underwent surgery, 3 had post-operative chemotherapy. Complete follow-up information was available with a median follow-up time of 56 months, with a range of 12–168 months. Five patients survived at least 4 years from the time of diagnosis. Conclusion: Long-term survival in patients with AC is possible.

Clinical manifestations of appendiceal pinworms in children: an institutional experience and a review of the literature.

The association of Enterobius vermicularis infestation with acute appendicitis varies from 0.2-41.8% worldwide. Our purpose was to determine the significance of Enterobius-associated appendicitis by retrospective review of appendectomies performed during a 5-year period at a major children's hospital. The Surgical Pathology database at Children's Hospital, Columbus, Ohio, was reviewed for appendiceal specimens found to have Enterobius infestation. Corresponding patient charts were evaluated for age, gender, presenting symptoms, laboratory data, operative findings, and clinical course. Of the 1,549 appendectomies performed from January 1998 through January 2003, 21 specimens (1.4%) were found to contain Enterobius vermicularis. Fifteen of the appendectomies were performed for symptoms of acute appendicitis; the remaining six were incidental appendectomies in conjunction with other operations. The mean age was 8.9 years. Ten patients were male; 11 were female. Of the 15 symptomatic children, nine presented with fever >99.0 degrees F, and 11 had a WBC count >10,000. Intra-operative appearance of the appendix ranged from normal to perforation. Pathologic evaluation showed neutrophil or eosinophil infiltration in 15 of the 21 specimens. Enterobius infestation is an uncommon cause of acute appendicitis in children in the United States. It may be associated with acute appendicitis, "chronic appendicitis," ruptured appendicitis, or with no significant clinical symptoms.

Mucinous cystadenoma of the appendix: diagnosis, surgical management, and follow-up

Purpose To review the diagnostic examination and clinical presentation of mucinous cystadenoma of the appendix. Methods Case report from experience at an Air Force tertiary care hospital in a 66-year-old woman with chronic right lower quadrant pain. Results After extensive preoperative evaluation and subsequent diagnostic laparoscopy, a right hemicolectomy was performed for a mucinous cystadenoma of the appendix. Conclusions Appendiceal mucinous cystadenoma is a rare entity found in only 0.3% of appendiceal specimens. Preoperative evaluation with radiologic and endoscopic methods is helpful but not always diagnostic. Although a benign disease process, complications from rupture, invasion into adjacent organs, or recurrence warrant adherence to strict oncologic principles for resection.

Immunocytochemical Analysis of Cellular Infiltrates in Human Appendicitis

This study was conducted to determine the immunologic cellular composition in human appendicitis and its association with the development of perforated appendicitis. Appendiceal specimens from 27 patients with acute appendicitis were immunostained to detect lymphocyte surface markers. Moreover, the lymphocyte surface markers of peripheral blood were analyzed by laser flow cytometry in 12 patients. Helper T lymphocytes (CD4) were present in all the patients, while B lymphocytes (CD19), natural killer (NK) cells (CD56), and cytotoxic T lymphocytes (CD8) were present in 7 (70%), 10 (100%), and 9 patients (90%) with perforated appendicitis, and in 12 (63.2%), 10 (58.8%), and 6 (54.5%) patients without perforation, respectively. There were significant differences between the patients with a perforated appendix and those without perforation, in the positivity rate for CD8 and CD56 cells (P < 0.05). The number of cells positive for CD56, being NK cells, in the blood from the patients with perforation was significantly lower than that in the blood from those without perforation (P < 0.05). The infiltration of a greater number of cytotoxic T lymphocytes and NK cells was observed in the appendices from patients with perforated appendicitis than in those from patients with nonperforated appendicitis.

Isolation of Yersinia enterocolitica from cases of acute appendicitis and ice-cream

Seventy (70) appendiceal specimens and 80 ice-cream samples were analysed to detect Yersinia enterocolitica using three different media. Both Y. enterocolitica and Citrobacter freundii were recovered in appendiceal specimens (17.1% and 8.6%) and ice-cream (26.25% and 18.75%) respectively. Thioglycollate medium was more selective and productive in isolating Yersinia. Y. enterocolitica was the major causative agent of acute appendicitis (11/25, 44%). It was sensitive to chloramphenicol, gentamicin, tetracycline and trimethoprim- sulfamethoxazole.

Helicobacter pylori does not play a role in the aetiology of acute appendicitis.

The aetiology of acute appendicitis remains uncertain. H. pylori is viable outside the gastroduodenum, however its pathological role outside this area has not been fully investigated. Ten consecutive patients with a histological diagnosis of acute appendicitis were investigated for H. pylori status by serology, and by culture, histology, and polymerase chain reaction (PCR) analysis of the appendiceal specimens. One patient had positive serology for H. pylori, however PCR analysis was negative. Culture failed to reveal H. pylori colonies. Histology in 5 cases did reveal organisms with a morphological appearance of H. pylori, but PCR analysis confirmed that H. pylori was not present. Using a variety of methods, with PCR acting as the 'gold standard', we have shown that H. pylori is not associated with acute appendicitis.

Characterisation of the Local Inflammatory Response in Appendicitis

SummaryIn this study we have characterised the local inflammatory response in acute suppurative appendicitis (S), focal appendicitis (F), and normal appendices (C). Enumeration of lymphocyte subpopulations, cells expressing IL‐2 receptor, natural killer (NK) cells, monocytes and plasma cell isotypes and subclasses infiltrating the lamina propria was carried out on all specimens using immunoperoxidase staining procedures. Total T cells were significantly increased in both acute suppurative appendicitis and focal appendicitis compared with controls (p &lt; 0.001). Cells infiltrating the lamina propria expressed IL‐2 receptor in all appendiceal specimens but were significantly increased in both acute and focal appendicitis (p &lt; 0.01). IgG and IgA plasma cell isotypes were significantly increased in all S and F appendiceal specimens (p &lt; 0.001). Monocyte and NK cell numbers, however, were only increased in acute suppurative appendiceal specimens. The increased lymphocyte and plasma cell isotypes seen in focal appendicitis occurred throughout the entire organ even though the inflammatory focus was confined to only three to seven serial sections. These results clearly show a differential pattern of cellular infiltration in focal appendicitis from that seen in acute suppurative appendicitis. The selective lymphocyte and plasma cell nature of the cellular infiltrate in the lamina propria of focal appendicitis may reflect the presence of a specific immune response to an as yet unidentified luminal antigen as a possible cause of appendicitis.

A microbiological comparison between acute and complicated appendicitis.

Bacteria recovered from appendiceal specimens from 20 patients with acute appendicitis were compared with those recovered from 19 patients with complicated (gangrenous or perforative) appendicitis. Specimens of both peritoneal fluid and appendiceal tissue from patients with acute appendicitis yielded smaller numbers and fewer species of bacteria in culture than did specimens from patients with more complicated disease (2.3 strains per specimen for the former; 9.9 strains per specimen for the latter). Bacteria were recovered from all 13 cultures of specimens of appendiceal tissue and from 13 of 18 cultures of specimens of peritoneal fluid obtained from patients with gangrenous and perforative appendicitis; however, only eight of 17 cultures of appendiceal specimens and seven of 18 cultures of peritoneal fluid specimens from patients with acute appendicitis yielded bacteria. These findings suggest that some bacteria traverse the intact appendiceal wall prior to perforation and that progressive infection and subsequent tissue damage and necrosis allow larger numbers and varieties of bacteria to move through appendiceal wall tissue and into the peritoneal cavity.

NEW INSICHTS INTO THE PATHOGENESIS OF APPENDICITIS BASED I.MUNOCYTOCHEMICAL ANALYSIS OF EARLY IMMUNE RESPONSE

Although appendicitis is the most common condition requiring surgery, the pathogenesis of this disease is poorly understood. In this study we investigated in an animal model and in humans, the possibility that an effector imnune response to local antigen stimulation could be a significant mechanism in the development of appendicitis.Polymorphonuclear leukocytes (PMN), plasma cells and T-cell infiltration was measured in 24 New Zealand bred white rabbits following experimental obstruction of the appendiceal lumen for periods ranging frcm 30 minutes to 24 hours. T-cell infiltration was the most dominant earliest infiltrating cell type of the lamina propria occurring at 30 minutes after obstruction. Significant infiltration (p<0.01) of the remaining cell types occurred as follows: IgM and IgG plasma cells at 30 minutes after obstruction and IgA and PMN at 2 hours.Lymphocyte infiltration was also seen as the earliest immunopathological event in a study of 15 acute suppurative appendiceal specimens and 5 specimens with only focal appendicitis compared to 5 histologically normal appendices. Equally significantly increased levels (p < 0.01) of TH cells, IL-2 positive cells as well as plasma cell isotypes IgG and IgA infiltration of the lamina propria was seen throughout the entire resected organ of patients with focal and acute suppurative appendicitis compared to histologically normal appendices.Significant PMN, monocyte and NK cell infiltration was only present in acute suppurative appendicitis. These fiiidings suggest the probability of a specific immune response to lumen derived antigens as a triggering factor in acute appendicitis.

Intussusception of the appendix.

Intussusception of the appendix is an uncommon occurrence. In 1967 Paul and Ferraro reviewed the literature and added three cases to the existing 119. In a recent review of 71,000 appendiceal specimens, Collins (1963) found seven instances (0·01 per cent) of intussusception of the appendix. Radiologic documentation has been only rarely illustrated (Skarby, 1941; Braun, 1962; Gorske, 1968). Two main types of appendiceal intussusception are described (Zeiter, 1951). The first is a limited intussusception of the more distal appendix into itself or a partial intussusception of the proximal appendix into the caput caecum. The second is complete invagination of the appendix into the caecum; occasionally, this may progress to result in a colo-colic and/or ileo-colic intussusception.