CinciHirsch - Pathology of Hirschprung Disease
With Dr. Margaret Collins & Dr. Alberto Pena & Dr. Raj Kapoor & Dr. Miguel Reyes-Mujica · hosted by Dr. Andrea Bischoff & Dr. Todd Ponsky · StayCurrentMD
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Educational content from recorded physician discussions — not medical advice. Talk to your (or your child's) care team about your situation.
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What the experts said
Ganglion cells are present in the rectal submucosa at 28 weeks gestation normally, though they may appear immature.
An experienced pediatric pathologist can recognize immature ganglion cells at 28 weeks gestation.
Suction rectal biopsies to rule out Hirschsprung disease on 28-week gestation newborns are extremely rare.
The failure rate for suction rectal biopsy increases after one year of age.
After infancy, there is increased separation of ganglia as a result of growth, making suction biopsy more difficult.
Beyond infancy, there is increased toughness of the stroma, making it more difficult to obtain a good suction rectal biopsy.
The anal canal becomes longer and thicker with age, contributing to increased suction biopsy failure rates.
If suction biopsy fails in children over one year, a deeper or full-thickness rectal biopsy should be considered as the first option.
Dr. Frykman was trained to stop attempting suction rectal biopsies at about 6 months of age and take patients to the operating room instead.
After 6 months of age, the clinical picture of Hirschsprung disease is often so obvious that suction biopsy becomes less relevant.
The suction rectal biopsy is not the main element for diagnosis but one extra piece of information, particularly useful in newborn babies.
Having hypertrophic nerves is helpful in the setting of no ganglion cells in an otherwise adequate suction rectal biopsy.
Communication between surgeon and pathologist is essential when deciding whether to proceed with surgery based on biopsy findings.
It is not a good idea to base an entire surgical procedure on the frozen section of a biopsy obtained intraoperatively.
A better approach is to obtain a full-thickness rectal biopsy without frozen section, allow permanent sections and adjunctive studies, then plan surgical resection at a future date.
When diagnosing Hirschsprung disease on suction rectal biopsy, the pathologist is committing that child to losing at least some rectum.
If a pathologist diagnoses Hirschsprung disease on suction biopsy and the surgeon finds ganglion cells at the peritoneal reflection, the patient still has short segment disease.
A pathologist must be very confident when diagnosing Hirschsprung disease on biopsy, recognizing the medicolegal implications if the diagnosis is wrong.
If there is any equivocation about the biopsy, clear communication with the surgeon is critical to discuss whether material is suboptimal or methods are inadequate.
An experienced pathologist can recognize immature ganglion cells, probably even at 28 weeks, though this is rarely requested in suction biopsies.
An experienced pathologist knows how to apply and interpret ancillary studies and, most importantly, knows when material is suboptimal.
Large nerves are not present in the submucosa of all cases of Hirschsprung disease; total colonic aganglionosis is a classic example.
It is possible to have a suction rectal biopsy showing absent ganglion cells without demonstrating large nerves in the submucosa.
When absent ganglion cells are found without hypertrophic nerves, the strength of clinical findings, biopsy adequacy, patient age, gender, contrast enema results, family history, and ancillary stains must all be considered.
Nerve hypertrophy may be less apparent in very young infants as well as in older children.
Ancillary studies are extremely helpful when there are conflicting or ambiguous results or suboptimal specimen adequacy.
If a patient has no ganglion cells and adequate submucosa but no hypertrophic nerves, a convincing abnormality in calretinin immunoreactivity or acetylcholinesterase staining can be enough to make the diagnosis of Hirschsprung disease.
Experienced pathologists develop a gestalt for recognizing too many, too big nerves rather than relying solely on measurements.
The 40-micron rule (nerves should not exceed 40 microns in diameter in distal rectum of infants under 6 months) is generally true but has rare exceptions, and does not hold in older children.
The pattern of nerve hypertrophy involves a shift in caliber of all nerves, with more intermediate, moderately enlarged, and markedly enlarged nerves in greater concentration than normal.
Pathologists should be brought more into the decision-making equation, considering not only histology but also clinical picture and radiological studies.
Complete communication between surgeons and pathologists will significantly reduce difficulties and possible errors.
Hirschsprung operations are too big to be made on a flimsy basis or with intraoperative improvisation like ordering frozen sections without a protocol.
In most hospitals, rectal biopsies are seen by more than one pathologist before a diagnosis is rendered.
At Cincinnati Children's, pathologists use a multi-headed microscope with a calibrated arrow to quickly measure nerve diameter during frozen sections without taking out calipers.
Transition zone characteristics include partial circumferential aganglionosis, which requires examining the whole circumference of bowel.
Transition zone contains ganglion cells that are not in their normal distribution completely around the circumference of the bowel.
Transition zone has hypoganglionosis by definition.
Transition zone has hypertrophic nerves that can be evaluated with calretinin stain, more in the submucosa than in the myenteric plexus, with or without associated ganglion cells.
Submucosal hyperganglionosis (many ganglion cells in one ganglion, at least 10) is a more controversial feature of transition zone, where submucosa can look like IND type B.
Ectopic ganglion cells can occur in normal biopsies and normally innervated bowel, making them a controversial transition zone feature.
A positive calretinin stain (showing nerve twigs in lamina propria) proximal to an aganglionic segment indicates ganglion cells are present even if not visible in that particular section.
The methodology used for IND diagnosis in Europe (15-micron thick sections, specific histochemical stains) has not been adopted in the United States.
IND has had inconsistent diagnostic criteria, with definitions changing several times over decades.
IND lacks adequate control data—studies have not compared constipated children to age-matched non-constipated controls to determine if features are causative.
IND should not be diagnosed in infants, is outgrown by age 4, does not require surgical therapy, and is self-correcting, making its clinical significance unclear.
Multiple authors have challenged whether IND diagnostic criteria represent one end of a normal spectrum.
The histopathological phenotype of IND may be a consequence or adaptation to downstream dysmotility rather than the cause.
In the United States, many features attributed to IND are considered transition zone in Hirschsprung disease.
There is not a single topographic study of intestinal neuronal dysplasia describing the anatomical extent of the histological abnormality.
Without topographic studies, there is no basis for resecting histologically abnormal portions of colon in IND, unlike in Hirschsprung disease where pathology determines resection extent.
The concept of IND is currently not clinically relevant, though there may be secrets in histological characterization of motility disorders to be studied in the future.
IND arose from the need to explain the subset of Hirschsprung patients with persistent symptoms after surgery.
IND was championed by a surgeon doing pathology rather than a pathologist, which is inappropriate.
IND should be considered a probably transitional developmental period in a subset of patients, not a condition requiring surgery.
Dr. Kapoor remains open-minded about whether there is an age-related change in the density of giant ganglia in the submucosa that is shifted in Hirschsprung patients.
Studying IND properly requires many patients, patience in counting ganglion cells, and huge effort to correlate findings with outcome while controlling for other variables.
The best way to diagnose hypoganglionosis is to consider only myenteric ganglion cell density, which requires resected bowel, not just suction biopsy.
Pathologists currently only confidently diagnose severe hypoganglionosis, based on long stretches of myenteric plexus containing small ganglia (one or two ganglion cells per ganglion) with minimal neuropil.
Less severe forms of hypoganglionosis can only be resolved for research purposes with dedicated ganglion cell counts using specific antibody markers.