© 2008 Caris Diagnostics, Inc. All rights reserved.
What Every Pathologist Wants the GI
Nurse to Know
(and how you can help us help you)
Jonathan N. Glickman MD PhD
Director, GI Pathology, Caris Diagnostics, Newton, MA
Associate Professor of Pathology, Harvard Medical School
© 2008 Caris Diagnostics, Inc. All rights reserved.
OUTLINE
• Introduction
• Overview of Anatomic Pathology Workflow
Procedures (i.e., what do pathologists do anyway?)
• Pathologist- Clinical Group Interactions
• Clinical and Endoscopic Information- the More the
Better!
• Sample Pathology Cases
© 2008 Caris Diagnostics, Inc. All rights reserved.
A little about myself…..• Washington University Medical
School, MD PhD 1995
• Brigham and Women’s Hospital
(BWH)
– Pathology residency
– GI pathology fellowship
• Staff pathologist, BWH and
Children’s Hospital
• Associate Professor of Pathology,
Harvard Medical School
• Director of GI Pathology, Caris
Diagnostics, Newton, MA
© 2008 Caris Diagnostics, Inc. All rights reserved.
Caris Pathology – Who are we?
• Three closely collaborating full-service laboratories (Irving, TX;
Newton, MA; Phoenix, AZ)
• 16 GI pathology fellowship-trained physicians
• 13 additional pathologists with GI expertise and fellowship
training in surgical pathology, cytopathology, or
hematopathology.
• Over 20 institutions represented:University of Washington, Baylor College of Medicine, Beth Israel Deaconess Medical Center, Brigham and
Women’s Hospital, Cleveland Clinic, Dallas VA Medical School, Duke University, Georgetown University, Harvard
Medical School, Indiana University, Johns Hopkins University, Mayo Clinic, M.D. Anderson Cancer Center,
Memorial Sloan-Kettering Cancer Center, University of Cincinnati, University of Iowa, University of Kansas,
University of Kentucky, University of Michigan, University of Nebraska Medical Center, University of Pittsburgh,
University of Southern California, University of Texas
© 2008 Caris Diagnostics, Inc. All rights reserved.
Pathology Practice
• Two basic venues for anatomic pathology practices
– Hospital based
– Non-hospital based (private lab/outpatient)
• Key differences
– Pathologist activities
– Types of specimens
– Nature of pathologist-clinician interactions
– Access to clinical and endoscopic information
© 2008 Caris Diagnostics, Inc. All rights reserved.
Anatomic Pathology Laboratory- Workflow
1. Receipt and Accessioning
- Patient identification
- Documentation of clinical history and endoscopic
findings
2. Gross examination and description of tissue
3. Tissue processing and embedding in paraffin
4. Sectioning/slide preparation and staining
5. Microscopic examination of slides
6. Preparation and release of pathology report
© 2008 Caris Diagnostics, Inc. All rights reserved.
Accessioning• Review received
paperwork
• Verify that
specimens received
match paperwork
• Verify patient info
• Correlate with pre-
accessioned cases
• Log into
information system
© 2008 Caris Diagnostics, Inc. All rights reserved.
Gross Description and Tissue Submission
• Trained Pathology
Assistant
• Review of paperwork,
submitted clinical
information
• Dictation
• Tissue sectioning (if
necessary)
• Placement in cassettes
© 2008 Caris Diagnostics, Inc. All rights reserved.
Tissue Processing/Embedding/Sectioning• Good tissue processing and
sectioning is paramount to a good consultation report
• Proper processing
– Additional fixation in formalin
– Progressive dehydration to allow paraffin permeation
• Tissue is embedded in paraffin blocks
• Paraffin saturation enables thin sections
– Acts a support medium
• Sectioned at 4-6 microns onto glass slides
• Technique matters!
© 2008 Caris Diagnostics, Inc. All rights reserved.
Slide preparation and staining• Taken through
deparaffinization,
rehydration, and drying
steps
• Once rehydrated, slides are
stained
© 2008 Caris Diagnostics, Inc. All rights reserved.
Tissue Sectioning
© 2008 Caris Diagnostics, Inc. All rights reserved.
Tissue Sectioning
© 2008 Caris Diagnostics, Inc. All rights reserved.
Tissue Sectioning
© 2008 Caris Diagnostics, Inc. All rights reserved.
Tissue Sectioning
© 2008 Caris Diagnostics, Inc. All rights reserved.
Microscopic examination• Integration of all
supplied information
• Formulation of
diagnosis
© 2008 Caris Diagnostics, Inc. All rights reserved.
Quality Control
• Patient identification errors
• Accurate clinical information
• Specimen loss
• Specimen mix-up
© 2008 Caris Diagnostics, Inc. All rights reserved.
Specimen labeling
• Please label clearly!
• Printed labels are
even better!
© 2008 Caris Diagnostics, Inc. All rights reserved.
What should a good GI biopsy pathology report
do?
© 2008 Caris Diagnostics, Inc. All rights reserved.
Final Diagnosis
• A summary medical interpretation based on the gross
and microscopic findings
• Incorporates supplied clinical history and endoscopic
information, results of prior pathology, etc.
• Standard terminology
– Classification systems
– Necessary for clear communication
• Must state all pertinent positive and negative findings
relevant to diagnosis
© 2008 Caris Diagnostics, Inc. All rights reserved.
Comment
• A narrative prominently placed in the pathology consultation
report that addresses clinical/pathologic correlations, pertinent
supportive evidence, prognostic information, references
• Answer the clinical question posed to the best of our ability
– Place histologic findings in clinical and endoscopic context
• Differential diagnosis, with preference if appropriate.
• Sufficient information to make meaningful treatment decisions
– Polyps- margins, high grade dysplasia
– Need for more tissue?
© 2008 Caris Diagnostics, Inc. All rights reserved.
An Informative Pathology Report
• Differentiates normal from abnormal
– Willing to call a biopsy normal!
• Provides all pertinent positives/negatives
– H. pylori, granulomas, dysplasia
• Makes as specific a diagnosis as possible (etiologic/with attention to current disease classifications and terminology)
• Establishes a correlation between clinical and pathologic findings
• Doesn’t leave the clinician hanging!
© 2008 Caris Diagnostics, Inc. All rights reserved.
The more information, the better!
© 2008 Caris Diagnostics, Inc. All rights reserved.
Endoscopic findings may (and often do)
influence pathologic evaluation
• Availability of endoscopy report (even better, with images)
• Examples
– Polyp vs. flat mucosa
– Barrett's mucosa in esophagus
– Appearance of duodenum (normal vs. abnormal, for celiac
disease)
– Severity and distribution of colitis
© 2008 Caris Diagnostics, Inc. All rights reserved.
Colonic polyps
Robbins & Cotran, 2005
Hyperplastic polyp
Adenoma
© 2008 Caris Diagnostics, Inc. All rights reserved.
Polyp vs. flat mucosal biopsy• Polyp mimics
– Mucosal folds
– Submucosal
lesions
– Lymphoid
aggregates
• Deeper levels for
small lesions
© 2008 Caris Diagnostics, Inc. All rights reserved.
“Polyp”- additional levels
• Small polyp identified endoscopically
• Tubular adenoma only on deeper levels
• Altered surveillance interval
Original
Deeper
© 2008 Caris Diagnostics, Inc. All rights reserved.
50 year-old woman with a 1.2 cm polyp
in the right colon
© 2008 Caris Diagnostics, Inc. All rights reserved.
Sessile serrated adenoma• Compared to hyperplastic
polyps:
– Larger
– Sessile
– Right sided
• Endoscopically subtle:
“thickened fold”
• Molecular abnormalities in
DNA mismatch repair:
“microsatellite instability”
© 2008 Caris Diagnostics, Inc. All rights reserved.
Newer polyp entities• Many bland polyps previously thought to be hyperplastic
polyps are actually pre-malignant lesions.
• Histologic difference between:
• large hyperplastic polyps
• traumatized hyperplastic polyps
• mixed hyperplastic-adenomatous polyps
• “traditional” serrated adenomas
• sessile serrated adenomas
• sessile serrated adenomas with dysplasia or carcinoma
© 2008 Caris Diagnostics, Inc. All rights reserved.
Polyp Margins
__Cold (forceps)__ ________Hot (snare)__________
Pedunculated Sessile
© 2008 Caris Diagnostics, Inc. All rights reserved.
“Distal esophagus” biopsy• “Barrett’s mucosa”?
• “Squamocolumnar
mucosa with intestinal
metaplasia”?
• Comment: “If this biopsy is
derived from endoscopically
abnormal mucosa in the
tubular esophagus, then the
presence of intestinal
metaplasia fulfills the
American College of
Gastroenterology diagnostic
criteria of Barrett’s
esophagus.”
© 2008 Caris Diagnostics, Inc. All rights reserved.
Barrett’s esophagus- additional levels
• Patient history of
heartburn
• “Tongues of
columnar mucosa”
• Intestinal metaplasia
only on deeper levels
• Patient now gets
appropriate
surveillance for
Barrett’s esophagus
© 2008 Caris Diagnostics, Inc. All rights reserved.
Barrett’s esophagus – no dysplasia
© 2008 Caris Diagnostics, Inc. All rights reserved.
Barrett’s esophagus – Low grade dysplasia Barrett’s esophagus – High grade dysplasia
© 2008 Caris Diagnostics, Inc. All rights reserved.
Location of Biopsies
• GI tract disorders in which distribution of disease is key to
recognition
– IBD
– Esophagitis (reflux vs. eosinophilic)
– Barrett’s esophagus
– Atrophic gastritis
• Knowing the location of biopsy is a key part of pathologic
evaluation
• Avoid pooling biopsies in one jar!
© 2008 Caris Diagnostics, Inc. All rights reserved.
Optimal/preferred endoscopic sampling
• IBD surveillance: Every 10 cm of involved colon, plus gross
lesions.
• Duodenum (for celiac): Multiple (at least 2-3 fragments)
• Stomach: Antrum and corpus
• Esophagus: Distal third and middle third (to exclude
eosinophilic esophagitis)
• Barrett’s esophagus: every 2 cm
© 2008 Caris Diagnostics, Inc. All rights reserved.
Eosinophilic esophagitis
© 2008 Caris Diagnostics, Inc. All rights reserved.
Diagnosis and classification of IBD
• Often not possible based on histologic examination alone.
• Clinical context is critical
• Distinction from mimics.
• Confounding effects of prior medical therapy, surgery.
• Prior of prior biopsies and/or resections may be helpful.
© 2008 Caris Diagnostics, Inc. All rights reserved.
Crohn’s disease vs. UC
•Organ involvement
•Distribution
•Layers involved
•Microscopic
© 2008 Caris Diagnostics, Inc. All rights reserved.
Subclassification of IBD
• Attempt to subclassify IBD
whenever possible
• Clinical and endoscopic
information always helpful
• Communication with
gastroenterologist
•
Sigmoid colon: “chronic colitis”
© 2008 Caris Diagnostics, Inc. All rights reserved.
Recognition of histologic mimics; clinical
history can distinguish
• 74 year-old woman presented with rectal bleeding
• Colonoscopy revealed rectal erythema and mucosal granularity
© 2008 Caris Diagnostics, Inc. All rights reserved.
H Ulcerative colitis
Patient G
© 2008 Caris Diagnostics, Inc. All rights reserved.
Ulcerative colitis- key histologic features• Architectural distortion
– Branching
– Irregularity
– Crypt atrophy
• Lymphoplasmacytic
infiltrate
• Neutrophilic activity
Normal
© 2008 Caris Diagnostics, Inc. All rights reserved.
Diagnosis
– Benign Anorectal Mucosa with Evidence of
Trauma/Prolapse
© 2008 Caris Diagnostics, Inc. All rights reserved.
Some innocuous processes that can mimic
IBD
• Mimics:
• Prolapse changes
• Healing ulcers
• Anastomotic site changes
• Chronic medication effect (e.g. NSAIDs)
• Chronic ischemia
• Patient was not labeled with a chronic colitis/proctitis or
neoplasm
• Inappropriate treatment with immunosuppressive agents was
avoided
© 2008 Caris Diagnostics, Inc. All rights reserved.
Diverticular disease associated colitis
© 2008 Caris Diagnostics, Inc. All rights reserved.
Missed diagnoses• 18 year-old woman with a clinical history of “ulcerative
colitis”
• Patient presents with diarrhea
© 2008 Caris Diagnostics, Inc. All rights reserved.
© 2008 Caris Diagnostics, Inc. All rights reserved.
Our diagnosis
– Lymphocytic Colitis
– Patient avoids potent immunosuppressive therapy, and
does not require lifetime endoscopic surveillance
© 2008 Caris Diagnostics, Inc. All rights reserved.
Conclusions
• Pathologic diagnosis does not occur in a vacuum
• High quality diagnosis (accurate and beneficial to patient care)
results from a team-oriented approach.
• The more we know, the better!
© 2008 Caris Diagnostics, Inc. All rights reserved.
THANK YOU