What Every Pathologist Wants the GI Nurse to Know (and how you can help us help you)

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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

Introduction OUTLINE 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

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

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

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

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

Review received paperwork Verify that specimens received match paperwork Verify patient info Correlate with preaccessioned cases Log into information system Accessioning

Gross Description and Tissue Submission Trained Pathology Assistant Review of paperwork, submitted clinical information Dictation Tissue sectioning (if necessary) Placement in cassettes

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!

Slide preparation and staining Taken through deparaffinization, rehydration, and drying steps Once rehydrated, slides are stained

Tissue Sectioning

Tissue Sectioning

Tissue Sectioning

Tissue Sectioning

Integration of all supplied information Formulation of diagnosis Microscopic examination

Quality Control Patient identification errors Accurate clinical information Specimen loss Specimen mix-up

Specimen labeling Please label clearly! Printed labels are even better!

What should a good GI biopsy pathology report do?

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

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?

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!

The more information, the better!

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

Colonic polyps Hyperplastic polyp Robbins & Cotran, 2005 Adenoma

Polyp mimics Polyp vs. flat mucosal biopsy Mucosal folds Submucosal lesions Lymphoid aggregates Deeper levels for small lesions

Polyp - additional levels Small polyp identified endoscopically Tubular adenoma only on deeper levels Altered surveillance interval Original Deeper

50 year-old woman with a 1.2 cm polyp in the right colon

Compared to hyperplastic polyps: Larger Sessile Right sided Endoscopically subtle: thickened fold Molecular abnormalities in DNA mismatch repair: microsatellite instability Sessile serrated adenoma

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

Polyp Margins Cold (forceps) Hot (snare) Pedunculated Sessile

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.

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

Barrett s esophagus no dysplasia

Barrett s esophagus Low grade dysplasia Barrett s esophagus High grade dysplasia

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!

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

Eosinophilic esophagitis

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.

Crohn s disease vs. UC Organ involvement Distribution Layers involved Microscopic

Subclassification of IBD Attempt to subclassify IBD whenever possible Clinical and endoscopic information always helpful Communication with gastroenterologist Sigmoid colon: chronic colitis

Recognition of histologic mimics; clinical history can distinguish 74 year-old woman presented with rectal bleeding Colonoscopy revealed rectal erythema and mucosal granularity

H Ulcerative colitis Patient G

Ulcerative colitis- key histologic features Architectural distortion Branching Irregularity Crypt atrophy Lymphoplasmacytic infiltrate Neutrophilic activity Normal

Diagnosis Benign Anorectal Mucosa with Evidence of Trauma/Prolapse

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

Diverticular disease associated colitis

Missed diagnoses 18 year-old woman with a clinical history of ulcerative colitis Patient presents with diarrhea

Our diagnosis Lymphocytic Colitis Patient avoids potent immunosuppressive therapy, and does not require lifetime endoscopic surveillance

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!

THANK YOU