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How to Approach Hirschsprung Disease
Raj P. KapurSeattle Children’s &
University of Washington
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Objectives
1. Diagnosis (based on rectal biopsy)
2. Intra-operative consultation
3. Post-operative surgical pathology
RECOMMENDATIONS
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Clinical History• 3 d old male• Failed to pass meconium in the first 48h• Abdominal distension and vomiting
• Barium enema shows dilated sigmoid and narrow rectum (recto-sigmoid ratio <1)
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Suction Rectal Biopsy
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RECTAL BIOPSY-BASED DIAGNOSISOF HIRSCHSPRUNG DISEASE
X
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TOO LOW(False Positive)
X
TOO HIGH(False Negative)
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Suction Biopsies from Multiple LevelsLess likely that all biopsies will lack sufficient submucosa
Fewer inadequate biopsies due to sampling of anal or transitional mucosa
Mapping data- "reposition" low biopsies- very short-segment HSCR
R1: Advise surgeon to get biopsies from multiple levels in separate containers
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IN MOST CASES H&E IS SUFFICIENT
CALRETININ
+
++
Adequate Bx
No Ganglion Cell
Nerve Hypertrophy
ExperiencedPathologist
= DIAGNOSIS
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3 mm
ADEQUACY
R2: Routinely cut lots of sections and have a low threshold for more levels
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Hypertrophic Submucosal NervesMonforte-Munoz et al. (1998) Arch Pathol Lab Med 122:721-5
Experience
R3: Pay careful attention to submucosal nerve calibers
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Ancillary Diagnostic Methods• Experience varies (recognition of ganglion cells,
especially immature cells, requires practice)
• Some biopsies have borderline adequacy
• Not all biopsies of aganglionic rectum contain hypertrophic nerves
• Histological quality varies
• Tissue sampling to exclude ganglion cells and large nerves is cumbersome and costly
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AChE (frozen) ChT (FFPE)
Agan
glio
nic
Gan
glio
nic
Kapur et alPediatr Dev Pathol 2017; 20:308-20
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RECOMMENDED APPROACH
controls
AgangGang
AgangGang
controls
patient patient
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Calretinin“2 cm”YOUR DIAGNOSIS?
A. Hirschsprung disease
B. Not Hirschsprung disease
C. RebiopsyD. Other
No ganglion cells
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Intact Calretinin Innervation Aganglionic Rectal Biopsies
Calretinin-immunoreactive mucosal nerves are present in the proximal 1-to-2 cm of the
aganglionic segment in HD may be present in aganglionic biopsies from
the distal rectum of a patient with vssHD
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Intact Calretinin Innervation Aganglionic Rectal Biopsies
R3: Pay careful attention to
submucosal nerve calibers!
HypertrophicNerves
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Recommendations
• Routinely obtain biopsies from more than one site • Perform calretinin ihc on at least one biopsy from
every patient• Pay close attention to nerve hypertrophy, even if
ganglion cells are present• In some situations (e.g., vssHSCR), AChE
histochemistry or ChT ihc may be particularly helpful• Have low threshold for rebiopsy and/or full-thickness
biopsy, especially in older patients
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Intraoperative Consultation
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L-HSCR(13%)
C-HSCR(7%)
S-HSCR(80%)
INTRAOPERATIVE LEVELLING BIOPSYFinding Ganglionic Bowel
5-10 mmIkeda & Goto (1984) Ann Surg 199:400-5
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HANDLING AND INTERPRETATION OF LEVELLING BIOPSY
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SP08-5984
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Orientation and location are important
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Myenteric Ganglion
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Set a high cytological threshold
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SP08-5984
Diff-Qwik Stain
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What do you advise the surgeon?
A. Do an appendectomy to exclude a skip area
B. Perform ileostomy or resection at this site
C. Obtain seromuscular biopsy of more proximal bowel to confirm ganglion cells are present
D. OtherGanglion cells are present
Levelling Biopsy
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Partial Circumferential Aganglionosis
Myenteric Hypoganglionosis
Submucosal Nerve Hypertrophy
Pelvic Gang
TRANSITION ZONE
In short-segment HSCR, the TZ is typically <5cm
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INTRAOPERATIVE HISTOPATHOLOGYExcluding Transition Zone
Find ganglion cells andmake anastomosis at least 5 cm proximal to that point
Conduct frozen section examination of donut from proximal margin to assess circumferential distribution of ganglion cells and submucosal nerve hypertrophy
≥5 cm
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INTRAOPERATIVE HISTOPATHOLOGYExcluding Transition Zone
Exclude Features of Transition Zone:Partial Circumferential AganglionosisMyenteric HypoganglionosisSubmucosal Nerve Hypertrophy
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MYENTERIC HYPOGANGLIONOSIS
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SUBMUCOSAL NERVE HYPERTROPHY
Coe et al. 2012
≥2 submucosal nerves per high power field with
diameters ≥40 µm
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3-STEP APPROACH
1. Levelling biopsy to find ganglion cells (identify a site oral to the aganglionic segment)
2. Surgeon should perform resection at least 5 cm proximal to levelling biopsy with ganglion cells
3. Frozen section of proximal margin to exclude features of transition zone
(Repeat 2 and 3 as needed)
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HANDLING THE RESECTION SPECIMEN
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SYNOPTIC REPORTING
https://hematogones.com/surg-path/hirsch
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