Caution in assessing histopathological opinions.

30 April 2010

As one of the pathologists in question, I wish to respond to some of the issues raised in the recent article by Brian Deer(1), and accompanying editorial by Nick Wright(2), on the histopathological aspects of autistic enterocolitis. There is some misrepresentation of my involvement and lack of understanding of the process in studies involving histopathology.

Firstly, at the time in question I was working solely for the NHS and acted as the key pathologist for the clinical gastroenterology paediatric team. I was not the lead pathologist for this, or any other Wakefield project.

Secondly, I was not responsible for reporting the majority of the biopsy specimens from the twelve children, initially written up in the Lancet paper(3). This period predated the advent of subspecialty reporting and a number of consultants, each with varying levels of expertise and gastroenterology interest, were responsible for reporting these cases. It is erroneous to consider these reports to be more accurate than any subsequent review. Nick Wright writes that there is nothing intrinsically wrong with such a review of the histopathology. I would state more strongly that ANY study of histopathology has more credence, with reduced inter- and intra-observer variation, when a systematic review, using defined structured criteria over a short time-frame, is performed.

As to the severity of any pathology, there was a gradual awareness by those attending the regular clinicopathological conferences that we were identifying subtle changes in some of the mucosal biopsies from autistic children. Subtle does not always indicate insignificant: the focal features of cow’s milk protein enteropathy may be misinterpreted as normal; the hidden pathogen in immunodeficient syndromes is identified only by close scrutiny; the presence of Helicobacter pylori in gastric biopsies was previously not recorded, as they were considered insignificant.

The significance of any minor changes cannot be determined at the outset; the natural history evolves and/or may be altered by any therapy, but the changes must first be recognised. It may not be widely appreciated that the separation of the upper limit of normal from the lower spectrum of abnormal in histopathology is not always clear cut (and not only in the gastrointestinal tract).

Without going into extensive detailed histopathological description, there does appear to be some confusion within the discussion of these cases. It should be appreciated that the term ‘colitis’ covers a range of changes from minimal, self-limiting and non-specific, to extensive, severe and characteristic; as such it is difficult to select a point from within a spectrum for a single definition. Reference was made to focal active colitis(4), although later it is stated that minor changes are not to be called colitis. In personal practice, as evidenced at the GMC hearing, I had a different threshold from the other co-authors who performed the review and translated those findings into words.

While a clinical gastroenterologist might consider caecal active inflammation with incipient crypt abscess formation to be normal in children(1), this is a significant finding to be recorded by pathologists. The dismissal of ‘a bit of architectural distortion’ as insignificant underscores the problem of histopathological complexity as this, in fact, is a key feature in the assessment of colonic biopsies(5).

Time may indeed bring greater clarity to our understanding of what, if any histopathological changes may be associated with autism.

References

1. Deer B. Wakefield’s ‘autistic colitis’ under the microscope. BMJ 2010; 340: 838-41.

2. Wright N. Does autistic enterocolitis exist? BMJ 2010; 340: 819-821.

3. Wakefield AJ, Murch SH, Anthony A, Linnell J, Casson DM, Malik M, et al. Ileal-lymphoid-nodular hyperplasia, nonspecific colitis, and pervasive developmental disorders in children. Lancet 1998; 351: 637-41.

4. Greenson JK, Stern RA, Carpenter SL, Barnett JL. The clinical significance of focal active colitis. Hum Pathol 1997;28:729-33.[

5. Jenkins D, Balsitis M, Gallivan S et al. Guidelines for the initial biopsy diagnosis of suspected chronic idiopathic inflammatory bowel disease. The British Society of Gastroenterology Initiative. J. Clin. Pathol. 1997; 50; 93–105.

Susan E Davies

Competing interests: None declared

Competing interests: None declared

Susan E Davies, Consultant Histopathologist

Addenbrooke's Hospital, Cambridge CB2 0QQ

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