The pathogenesis of Parkinson’s disease (PD) involves the accumulation of aggregated α-synuclein, which has been suggested to begin in the gastrointestinal tract.
Here, we determined the capacity of the appendix to modify PD risk and influence pathogenesis. In two independent epidemiological datasets, involving more than 1.6 million individuals and over 91 million person-years, we observed that removal of the appendix decades before PD onset was associated with a lower risk for PD, particularly for individuals living in rural areas, and delayed the age of PD onset.
We also found that the healthy human appendix contained intraneuronal α-synuclein aggregates and an abundance of PD pathology-associated α-synuclein truncation products that are known to accumulate in Lewy bodies, the pathological hallmark of PD.
Lysates of human appendix tissue induced the rapid cleavage and oligomerization of full-length recombinant α-synuclein. Together, we propose that the normal human appendix contains pathogenic forms of α-synuclein that affect the risk of developing PD.
Significance of acquired diverticular disease of the vermiform appendix: a marker of regional neoplasms?
To assess the prevalence of acquired diverticulum of the appendix (DA), including incipient forms and its possible significance as a marker of local/regional neoplasms.
The pathology database at Hvidovre Hospital was searched for appendix specimens, received between 2001 and 2010, coded for DA or for a space-occupying lesion. Slides were reviewed to determine DA status and the nature of lesions possibly causing DA.
Among 4413 appendix specimens, DA were identified in 39 (0.9%, CI 0.6% to 1.2%) cases, 17 (43.6%, 28.0% to 59.2%) of which additionally harboured an appendiceal neoplasm/neoplastic precursor, whereas this figure was 1.2% (CI 0.9% to 1.6%) for non-DA specimens (p<0.0001).
Six of the 39 DA specimens comprised incipient DA, three of which coexisted with appendiceal neoplasms. In addition, local/regional non-neoplastic lesions (six cases) and colorectal carcinomas (four cases) coexisted with DA.
DA has significance as a putative marker of local/regional neoplasms. Therefore, a DA specimen proved significantly more likely to harbour a neoplastic growth than a non-DA counterpart.
Submission for microscopy of the entire DA specimen, whether transmural or only incipient, and a comment in the pathology report on the occasional concurrence of local/regional neoplasms in this setting seem appropriate. The observation of DA may thus provide a valuable contribution in the diagnostic process.
Diverticular disease of the vermiform appendix: a diagnostic clue to underlying appendiceal neoplasm.
Acquired diverticula of the vermiform appendix are rare and arise as a result of different pathogenetic mechanisms. One of the etiologies includes proximally located, often unsuspected small neoplasms. Although the association of appendiceal diverticulosis and neoplasia is known, it remains underemphasized in the teaching and practice of surgical pathology.
To investigate the frequency of appendiceal neoplasms with acquired diverticulosis, we conducted a retrospective analysis of all appendectomy specimens received in our institution for a 55-month period (January 2002-July 2006). A total of 1361 appendectomy specimens were identified.
Diverticulosis was diagnosed in 23 (1.7%) of all cases. Eleven (48%) appendectomy specimens with diverticulosis also harbored an appendiceal neoplasm. The association of appendiceal neoplasms with diverticulosis was statistically significant (P < .0001, 2-sided Fisher exact test).
Neoplastic processes included 5 well-differentiated neuroendocrine tumors (carcinoids), 3 mucinous adenomas, 1 tubular adenoma, and 2 adenocarcinomas.
In one case, routine representative sections sampled only a small focus of carcinoma, which originally went undiagnosed.
We stress the need for meticulous gross assessment with histologic examination of the entire appendectomy specimen in cases of appendiceal diverticulosis. A thorough examination is required to rule out an underlying neoplasm as a cause of diverticulosis.
As acquired diverticula represent a rare finding, examination of the entire appendix in this setting does not create a significant impact on the workload within the pathologic laboratory.
Crohn’s disease limited to the vermiform appendix.
Thirteen cases of Crohn’s disease confined to the vermiform appendix were seen during a 12-year period. They constituted 16.9% of patients with primary resection of the bowel for Crohn’s disease in the same period, but only 0.4% of the cases of acute appendicitis.
In 10 of the 13 cases there was marked fibrous thickening of the appendiceal wall, and in 11 there were epithelioid cell granulomas. Appendectomy was performed in all cases.
None had postoperative fistula or later manifestations of the disease within the observation time averaging 6.3 years. The recurrence rate was previously believed to approach that of recurrence after resection in other parts of the intestines.
Collective review of this and three other relatively large case series gave an estimated recurrence rate of 3.5%. We conclude that in Crohn’s disease initially confined to the appendix the course appears to be indolent.
Granulomatous disease in the vermiform appendix.
In a twenty-year period 19 appendicectomy specimens were diagnosed as primary Crohn’s disease. This represents 4.9% of the total number of both resection specimens and mucosal biopsies diagnosed as Crohn’s disease during that time.
This is a review of the main histopathological features found in these appendices and their subsequent clinical outcome. The predominant feature is transmural inflammation characterised by fibrosis and giant cell epithelioid granulomata.
An accompanying spectrum of acute inflammatory changes is also seen. One patient progressed to more widespread ileal and caecal disease 17 months later.
One patient developed perianal fistulae and chronic non-specific proctitis 24 months later. This represents a proven recurrence of one case in a study population of 19.
The conclusion is that primary Crohn’s disease of the appendix is usually an isolated phenomenon but rarely it may forewarn of more widespread bowel disease in the future. A discussion regarding the differential diagnosis of granulomatous appendiceal lesions is included.
Primary adenocarcinoma of the vermiformappendix masquerading as Crohn’s disease. Case report.
A case of primary appendiceal adenocarcinoma is reported in a 30-year-old man presenting with clinical and radiological features of Crohn’s disease. Conditions simulating Crohn’s disease radiologically are discussed and the need for histological confirmation of Crohn’s disease managed conservatively is stressed.
Expanding the geographic distribution of the freshwater parasite Ceratomyxa (Cnidaria: Myxozoa) with vermiform-type plasmodia
Although species of the genus Ceratomyxa Thélohan, 1892 mostly parasitize marine fish around the world, a surprising diversity of the genus has recently been reported from Amazonian freshwater fish.
In this study, we report a freshwater Ceratomyxa species parasitizing Hemiodus orthonops (Hemiodontidae) from the Paraná River (La Plata Basin) in a watershed flowing into the southern part of South America, which expands the geographic distribution of this fish parasite in the freshwater resources of the continent.
We applied a combination of morphological, small subunit ribosomal DNA (SSU rDNA), and phylogenetic analyses, and vermiform-shaped plasmodia endowed with motility were found swimming in the bile of the fish. The characteristics of the plasmodia and myxospores of the Ceratomyxa species found in the Paraná River resembled those of Ceratomyxa fonsecai, a parasite of the congeneric host Hemiodus unimaculatus from the Tocantins River basin in northern Brazil.
Due to the close morphological and morphometric resemblances and the impossibility of genetic comparison, the parasite found in H. orthonops from the Paraná River was designated as Ceratomyxa cf. fonsecai, and the definition of its taxonomic status was left for further study.
|Vermiform appendix disease spectrum (vermiform appendix tumor progression) tissue array from TissueArray|
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Maximum likelihood and Bayesian analyses showed Ceratomyxa cf. fonsecai clustering within a well-supported clade, together with other Amazonian freshwater ceratomyxids. The present study suggests that shifts of the complex host/parasite between marine and freshwater environments were facilitated by marine incursions into South America in the Early Miocene.