Gastrointestinal Pathology E-Book

• Herausgeber: John Wiley & Sons
• Kategorie: Fachliteratur
• Sprache: Englisch

Seitenzahl: 917

Veröffentlichungsjahr: 2021

Beschreibung

An illustrated guide to best practices when performing and assessing biopsies for GI conditions of all kinds

Accurate diagnosis of GI conditions necessarily entails both the careful taking of biopsies and the informed analysis of tissue material. With that being so, gastroenterologists and GI pathologists alike must have a solid understanding of the techniques, handling requirements, and diagnostic characteristics involved if they are to collaborate effectively. Gastrointestinal Pathology has been designed to provide a clinically focussed and richly illustrated guide to real-world scenarios faced by practicing GI specialists, offering step-by-step instruction and professional advice on the correct diagnosis of all major GI conditions. This essential new book includes:

• Full-color illustrations throughout
• Complete details of biopsy samples required to diagnose specific conditions
• Reviews of differential diagnoses
• Clinical management clues based on pathologic findings

Featuring information to improve the practice of all gastroenterologists and GI pathologists, Gastrointestinal Pathology is a practical and every-day resource for the precise diagnosis of a wide range of GI conditions.

Leseprobe

Table of Contents

Cover

Title Page

Copyright Page

List of Contributors

1 General Principles of Biopsy Diagnosis of GI Disorders

Endoscopic Equipment for Tissue Sampling

Pinch Biopsy Forceps

Endoscopic Snare Devices

Endoscopic Brush Cytology

Endoscopic Fine‐Needle Aspiration (FNA) Devices

Tissue Processing in the Endoscopy Laboratory

Non‐oriented Samples

Oriented Samples

Cytology Samples

Culture Samples

Specific Organ Sampling Methods

Summary

Further Reading

2 Esophagus Inflammatory Conditions

Normal Histology, Variations

Infectious Esophagitis

Gastroesophageal Reflux Disease

Eosinophilic Esophagitis

Lymphocytic Esophagitis

Drug‐Induced Esophagitis

Sloughing Esophagitis

Graft Versus Host Disease of the Esophagus

Radiation Esophagitis

Dermatological Diseases Involving the Esophagus

Esophagitis and Inflammatory Bowel Disease

Further Reading

3 Epithelial Metaplastic, Polypoid, and Neoplastic Conditions of the Esophagus

Barrett’s Esophagus

Barrett’s Esophagus–Dysplasia—Esophageal Adenocarcinoma

Squamous Cell Dysplasia and Carcinoma

Epithelial Polyps

Heterotopias

Glycogenic Acanthosis

Mesenchymal Polyps

Leiomyoma and Leiomyosarcoma

Giant Fibrovascular Polyp

Gastrointestinal Stromal Tumor

(

GIST

)

Hemangioma

Kaposi Sarcoma

Miscellaneous Tumors

Esophageal Lymphoma

Further Reading

4 Inflammatory Disorders of the Stomach

Helicobacter‐Associated Gastritis and Peptic Ulcer Disease

Acute (Erosive/Hemorrhagic) Gastritis

Chemical (Reactive) Gastritis/Gastropathy

Granulomatous Gastritis

Gastritides with Prominent Lympho(plasma)cytic Infiltrate

Infectious Gastritis

Eosinophilic Gastritis

Collagenous Gastritis

Iatrogenic Gastritis

Vascular Gastropathy

Hypertrophic Gastropathy

Further Reading

5 Polyps of the Stomach

Fundic Gland Polyps (FGPs)

Hyperplastic Polyps

Gastric Adenoma

Juvenile Polyps

Peutz–Jeghers Syndrome

Cowden's Disease

Cronkhite–Canada Syndrome

Gastric Adenocarcinoma and Proximal Polyposis of the Stomach (GAPPS)

Nonepithelial and Malformative Polypoid Lesions

Lipoma

Xanthoma

Gastric Heterotopic Pancreas

Menetrier's Disease

Further Reading

6 Gastric Neoplastic Conditions

Dysplasia in Gastric Mucosa

Early Gastric Cancer

Adenocarcinoma of the Stomach

Neuroendocrine Tumors

Neuroendocrine Carcinoma

Nonepithelial Tumors

Further Reading

Gastric Neoplastic Conditions

Further Reading

7 Inflammatory and Miscellaneous Conditions of the Small Intestine

Inflammatory Conditions

Microvillus Inclusion Disease

Intestinal Epithelial Dysplasia (Tufting Enteropathy)

Acrodermatitis Enteropathica

Infections

Cryptosporidiosis

Isospora

Microsporidiosis

Strongyloidiasis

Mycobacterial Infection—

Mycobacterium avium

Intracellulare Complex (MAIC) and

Mycobacterium tuberculosis

Whipple's Disease

Yersiniosis

Adenovirus

Cytomegalovirus

Human Immunodeficiency Virus

Celiac Disease

Autoimmune Enteropathy

Tropical Sprue

Small Intestinal Bacterial Overgrowth

Chronic Variable Immunodeficiency (CVID)

Selective IgA Deficiency

Graft Versus Host Disease

Collagenous Sprue

Refractory Celiac Disease (RCD)

Crohn's Disease

Food Protein‐Induced Enteropathy

Eosinophilic Enteritis

Histiocytic/Granulomatous Enteritis

Necrotizing Enterocolitis (NEC)

Intestinal Ischemia (Syn. Ischemic Enteritis)

Radiation Enteritis

Peptic Duodenitis

NSAID Enteropathy

Isolated Ileitis/Erosion

Behcet's Disease

Cryptogenic Multifocal Ulcerating and Stenosing Enteritis

(

CMUSE

)

Miscellaneous Disorders

Deposition Disorders

Amyloidosis

Abetalipoproteinemia

Further Reading

8 Polyps of the Small Intestine

Heterotopia

Hamartoma

Endometriosis

Pseudopolyp (Benign Mucosal Polyp, Inflammatory Pseudopolyp)

Mucosal Prolapse Type Polyps

Brunner's Gland Cyst

Polyposis Syndromes

PTEN Hamartoma Tumor Syndrome (Syn. Cowden Syndrome)

Lymphoid Hyperplasia

Pneumatosis Intestinalis

Nonneoplastic Vascular Lesions

Further Reading

9 Epithelial and Nonepithelial Neoplasms of the Small Intestine

Adenoma

Pyloric Gland Adenoma

Intestinal Type Adenoma

Serrated Polyps

Carcinoma

Adenocarcinoma of Pyloric Gland Type

Neuroendocrine Neoplasms (Well‐Differentiated Neuroendocrine Tumors (NET), Neuroendocrine Carcinoma (NEC), Mixed endocrine‐non‐endocrine neoplasms (MiNEN))

Gangliocytic Paraganglioma

Gastrointestinal Stromal Tumor (GIST)

Inflammatory Fibroid Polyp

Other Mesenchymal Tumors

Lymphoma

B‐Cell Non‐Hodgkin Lymphoma

T‐Cell/NK‐T Cell Non‐Hodgkin Lymphoma

Hodgkin Lymphoma

Hematopoetic Disorders with Plasmacytic Differentiation

Plasmablastic Lymphoma

Lymphoplasmacytic Lymphoma

Other Hematopoetic Disorders

Leukemia

Histiocytic Disorders

Metastases to the Small Intestine Mucosa

Further Reading

10 Inflammatory Conditions of the Colon

Non‐Idiopathic Inflammatory Colitides

Pseudomembranous Colitis and Antibiotic‐Associated Diarrhea and Colitis

Brainerd Diarrhea

Parasites

Helminthic Infections

Sexually Transmitted Infections

Etiology of Colitis with Pattern Recognition

Treatment/Prognosis/Evolution

Radiation Proctocolitis

Treatment/Prognosis/Evolution

Neutropenic Enterocolitis (Typhlitis)

Treatment /Prognosis / Evolution

Variant Patterns of Collagenous Colitis have been Reported

Findings in Other Segments of the Gastrointestinal Tract

Colonic Diverticulosis and Diverticular Colitis

Mucosal Prolapse/Solitary Rectal Ulcer Syndrome (MPSRUS)

Pneumatosis Coli

Treatment/Prognosis/Evolution

Phlegmonous Colitis

Obstructive Colitis

Drug‐Associated and Iatrogenic Colitis

Eosinophilic Conditions Affecting the Colon

Mastocytic Enterocolitis

Graft Versus Host Disease (GVHD)

Further Reading

Inflammatory Bowel Disease

Definition, General Features, Predisposing Factors

Clinical and Endoscopical Features

Microscopic Findings

Morphologic Variants of UC and CD

Crohn's Disease

Differential Diagnosis

Treatment/Prognosis/Evolution

Further Reading

Dysplasia in Inflammatory Bowel Disease

Definition, General Features, Predisposing Factors

Clinical Features/Endoscopic Characteristics

Microscopic Features

Architectural Features

Cytological Features

Variant Patterns

The Classification and Grading of Dysplasia

Differential Diagnosis

Role of Immunohistochemistry

Treatment and Prognosis

Further Reading

11 Polyps of the Large Intestine

Epithelial Polyps

Inflammatory Polyps

Hamartomatous Polyps

Mesenchymal Polyps

Miscellaneous Polyps

Further Reading

12 Epithelial Neoplasms of the Large Bowel

Colorectal Carcinoma

Malignant Colorectal Polyp

Neuroendocrine Neoplasms

Lymphomas of the Large Bowl

Further Reading

13 Inflammatory Conditions of the Anus

Anal Fissure

Hemorrhoids

Anal (Rectal) Tonsil

Hidradenitis Suppurativa

Anal Abscess and Fistula

Inflammatory Bowel Disease

Anorectal Tuberculosis

Syphilis

Clinical Features and Endoscopic Characteristics

Lymphogranuloma Venereum

Granuloma Inguinale

Chancroid

Herpes Simplex Virus

Further Reading

14 Polyps and Neoplastic Lesions of the Anus

Inflammatory Cloacogenic Polyp

Fibroepithelial Polyp

Hidradenoma Papilliferum

Squamous Hyperplasia and “Leukoplakia”

Condyloma Acuminatum

Anal Intraepithelial Neoplasia (AIN)/

Anal Squamous Intraepithelial Lesion

(

ASIL

)

Perianal Intraepithelial Neoplasia (PAIN), Bowen's Disease, and Bowenoid Papulosis

Extramammary Paget's Disease

Squamous Cell Carcinoma

Verrucous Carcinoma (Giant Condyloma of Buschke and Löwenstein)

Adenocarcinoma

Malignant Melanoma

Miscellaneous and Rare Tumors

Further Reading

Index

End User License Agreement

List of Tables

Chapter 2

Table 2.1 Normal esophageal mucosa.

Table 2.2 Histologic features of GERD.

Table 2.3 Definition of eosinophilic esophagitis and diagnostic criteria.

Table 2.4 Endoscopic and histologic features of the major causes of infectiou...

Table 2.5 Conditions associated with esophageal eosinophilia in the different...

Table 2.6 Conditions associated with esophageal lymphocytosis (lymphocytic es...

Table 2.7 Medications implicated in causing esophagitis and histologic featur...

Table 2.8 Dermatologic diseases involving the esophagus.

Table 2.9 Histologic features of bullous diseases involving the esophagus.

Chapter 3

Table 3.1 Histologic features of columnar mucosa suggesting esophageal origin...

Table 3.2 Goblet cell mimics.

Table 3.3 Histological features in the assessment of mucosal biopsies for dys...

Table 3.4 Histologic features of reactive squamous epithelium vs. dysplasia.

Table 3.5 Miscellaneous esophageal polyps and polypoid lesions.

Chapter 4

Table 4.1 Overview of differential diagnoses to be considered in the setting ...

Table 4.2 Overview of different types of amyloidosis and associated condition...

Table 4.3 Showing several nonneoplastic and neoplastic conditions causing gia...

Chapter 5

Table 5.1 Overview of polypoid changes in syndromic settings.

Table 5.2 Immunohistochemical findings in inflammatory fibroid polyps.

Chapter 6

Table 6.1 An overview of familial syndromes associated with an increased risk...

Table 6.2 An overview of rare gastric malignancies with short histological de...

Table 6.3 Recommendations of HER2 immunohistochemical interpretation.

Table 6.4 Immunohistochemical panel for mimickers of poorly cohesive gastric ...

Table 6.5 The grading system of NET according to the WHO.

Table 6.6 Risk stratification of gastric gastrointestinal stromal tumors usin...

Table 6.7 Few examples of soft tissue tumors with possible histomorphological...

Table 6.8 Main histological types of primary gastric lymphomas.

Table 6.9 Wotherspoon scoring system for gastric lymphoid infiltrates.

Table 6.10 Differential diagnosis of small B‐cell lymphomas involving the sto...

Table 6.11 Differential diagnosis of high‐grade mature B‐cell lymphomas invol...

Chapter 7

Table 7.1 Intraepithelial lymphocytosis with normal villous architecture – ca...

Table 7.2 Modified Marsh classification scheme.

Table 7.3 Villanicci–Corazza classification scheme.

Table 7.4 Intraepithelial lymphocytosis with villous blunting/flat mucosa—cau...

Table 7.5 Grading of GVHD.

Table 7.6 Differentiating features of celiac disease and refractory celiac di...

Table 7.7 Causes of eosinophilic infiltration in small bowel.

Table 7.8 Common causes of histiocytic and granulomatous infiltration.

Table 7.9 Etiologies of ischemic disease.

Table 7.10 Major types of amyloid affecting the small intestine.

Chapter 9

Table 9.1 WHO classification of small intestinal and ampullary tumors.

Table 9.2 Conditions associated with an increased risk of small intestinal ca...

Table 9.3 Immunophenotypic classification of small intestinal adenocarcinoma.

Table 9.4 Features differentiating proximal and distal intestinal neuroendocr...

Table 9.5 Diagnostic criteria for NENs (including NET, NEC, MiNEN) adapted to...

Table 9.6 Gene mutational profile of c‐KIT.

Table 9.7 Characteristics of PDGFA mutated GIST.

Table 9.8 Characteristics of BRAF mutated GIST.

Table 9.9 Characteristics of SDH deficient GIST.

Table 9.10 Mesenchymal neoplasms entering the differential diagnosis of GIST.

Table 9.11 Risk of progressive disease in GISTs according to mitotic index, s...

Table 9.12 Histological differential diagnosis of inflammatory fibroid polyp.

Table 9.13 Other mesenchymal tumors entering the differential diagnosis of in...

Table 9.14 Primary small intestinal non‐Hodgkin lymphoma and frequency compar...

Table 9.15 B‐cell lymphoma—immunohistochemical and molecular features.

Table 9.16 Classification of post‐transplant lymphoproliferative disorder (PT...

Table 9.17 Diagnostic criteria for systemic mastocytosis.

Table 9.18 Histiocytic disorders of the small intestine.

Chapter 10

Table 10.1 Selected antibodies and PCR assays useful in the diagnosis of infe...

Table 10.2 Differential diagnosis of acute infectious‐type (self‐limiting) co...

Table 10.3 Range of histologic patterns on endoscopic biopsy of common bacter...

Table 10.4 Distinguishing features between TB,

Yersinia

and Crohn's disease.

Table 10.5 Differential diagnosis of acute ischemic colitis.

Table 10.6 Differential diagnosis of diffuse histiocytic infiltrates of the g...

Table 10.7 Fungal infections with spore formation in tissue sections.

Table 10.8 Causes of granulomatous inflammation in the colon and rectum.

Table 10.9 Predisposing and etiologic factors for ischemic colitis.

Table 10.10 Differential diagnosis of chronic ischemia.

Table 10.11 Risk factors for pseudomembranous colitis.

Table 10.12 Diseases associated with focal active colitis.

Table 10.13 Risk factors for radiation colitis.

Table 10.14 Differential diagnosis of radiation.

Table 10.15 Risk factors for neutropenic colitis.

Table 10.16 Autoimmune disease associated with collagenous and lymphocytic co...

Table 10.17 Drugs that may be associated with microscopic colitis.

Table 10.18 Differential diagnosis of collagenous colitis (CC).

Table 10.19 Differential diagnosis for lymphocytic colitis.

Table 10.20 Pitfalls in the diagnosis of lymphocytic and collagenous colitis.

Table 10.21 Risk factors for diverticular disease.

Table 10.22 Complications of diverticular disease.

Table 10.23 Distinguishing misplaced glands from invasive adenocarcinoma.

Table 10.24 Predisposing conditions for pneumatosis coli.

Table 10.25 Spectrum of reaction patterns in drug‐associated colitis.

Table 10.26 Pattern of drug related injury and examples of associated drugs.

Table 10.27 Important groups of drugs associated with colonic mucosal injury.

Table 10.28 Classification of eosinophilic colitis.

Table 10.29 Differential diagnosis of eosinophilic colitis.

Table 10.30 Predictive factors for GVHD.

Table 10.31 Signs and symptoms of chronic GVHD.

Table 10.32 Recommendations for final diagnosis.

Table 10.33 Features of Ulcerative colitis (UC) vs. Crohn’s disease (CD).

Table 10.34 Differential diagnosis of inflammatory bowel disease.

Table 10.35 Summary of recommendations for management of IBD‐associated dyspl...

Chapter 12

Table 12.1 Environmental factors affecting the risk of colorectal carcinoma.

Table 12.2 Genetic conditions associated with a risk of colorectal carcinoma.

Table 12.3 Histological classification of colorectal carcinoma according to t...

Table 12.4 Classification of colorectal carcinomas according to molecular cha...

Table 12.5 Adverse histologic parameters in malignant colorectal polyps resec...

Table 12.6 Grading of neuroendocrine tumors/carcinomas of the colon according...

Table 12.7 Most common lymphomas of the colon.

Chapter 14

Table 14.1 Comparison of the two‐tiered (squamous intraepithelial lesion) and...

Table 14.2

American Joint Committee on Cancer

(

AJCC

), 8th edition TNM staging for...

List of Illustrations

Chapter 1

Figure 1.1 Endoscope with control handle and tip. The tip contains a light s...

Figure 1.2 Endoscopic processor, which converts the light captured from the ...

Figure 1.3 (a) Tools for performing endoscopic resection including endoscopi...

Figure 1.4 Endoscopic biopsy forceps in the open position. The needle‐like p...

Figure 1.5 Micro biopsy forceps <1 mm in diameter, which can be passed throu...

Figure 1.6 Endoscopic snare for polypectomy. The wire loop is extended in th...

Figure 1.7 Endoscopic cytology brush. Note the abrasive brush extended beyon...

Figure 1.8 Nonendoscopic abrasive cytology brush.

Figure 1.9 (a) and (b) Endoscopic ultrasound endoscope and guided fine‐needl...

Figure 1.10 Pinned and oriented resection tissue from Barrett's esophagus‐as...

Figure 1.11 Barrett's esophagus with flat neoplasia (9 o'clock) for targeted...

Figure 1.12 Multiband mucosectomy device. The black rubber bands are mounted...

Figure 1.13 Area of resection at 6–12 o'clock includes the entire region of ...

Figure 1.14 Endoscopic submucosal dissection (ESD) procedure. A flat neoplas...

Figure 1.15 Endoscopically resected en bloc well‐differentiated adenocarcino...

Figure 1.16 Large mediastinal lymph node sampled with EUS‐FNA. The needle is...

Chapter 2

Figure 2.1 Endoscopic appearance of distal esophagus with normal squamous mu...

Figure 2.2 Normal esophagus squamous mucosa with normal stratified non‐kerat...

Figure 2.3 Endoscopic appearance of white exudate typical of

Candida albican

...

Figure 2.4 Debris of slough off superficial squamous epithelium with fungal ...

Figure 2.5 PAS stain of Figure 2.4 illustrating the fungal elements of

Candi

...

Figure 2.6 Multinucleated basal keratinocytes typical of HSV esophagitis.

Figure 2.7 Erosive esophagitis with prominent granulation and atypical cellu...

Figure 2.8 High‐magnification evaluation of Figure 2.7 demonstrated (a) endo...

Figure 2.9 Endoscopic appearance of erosive esophagitis in a patient with ga...

Figure 2.10 Characteristic appearance of low‐power view of reflux esophagiti...

Figure 2.11 High‐power magnification of reflux esophagitis with basal cell h...

Figure 2.12 Endoscopic appearance of eosinophilic esophagitis (a) with so‐ca...

Figure 2.13 Characteristic histology of eosinophilic esophagitis with basal ...

Figure 2.14 Characteristic histology of lymphocytic esophagitis.

Figure 2.15 Endoscopic appearance of inflammatory stricture of the esophagus...

Figure 2.16 (a) Iron tablet erosive esophagitis with fibrinopurulent debris....

Figure 2.17 Endoscopic appearance of necrotizing esophagitis with appearance...

Figure 2.18 Characteristic appearance of sloughing esophagitis with two‐tone...

Figure 2.19 Endoscopic appearance of acute GVHD of esophagus with diffuse mu...

Figure 2.20 Endoscopic appearance of inflammatory stricture with persistent ...

Figure 2.21 Microscopic appearance of acute GVHD of esophagus with basal apo...

Figure 2.22 Endoscopic appearance of esophageal lichen planus with diffuse m...

Figure 2.23 Esophageal granuloma in a previously diagnosed patient with Croh...

Chapter 3

Figure 3.1 Endoscopic view of Barrett's esophagus. From upper left and clock...

Figure 3.2 (a) Typical appearance of Barrett's esophagus with numerous goble...

Figure 3.3 Barrett's esophagus indefinite for dysplasia. Nuclear hyperchroma...

Figure 3.4 Low‐grade dysplasia. Note the sharp transition between nuclear hy...

Figure 3.5 High‐grade dysplasia. The architectural features with back to bac...

Figure 3.6 Crypt dysplasia. This lesion is characterized by neoplastic featu...

Figure 3.7 (a) Foveolar dysplasia, low grade. This lesion is characterized b...

Figure 3.8 Serrated dysplasia—note the serrated profile of the glands with l...

Figure 3.9 (a) Intramucosal adenocarcionma—the lesion is characterized by di...

Figure 3.10 Duplicated muscularis mucosae—note the inner and outer (duplicat...

Figure 3.11 (a) Barrett's esophagus with high‐grade dysplasia in the 8–12 o'...

Figure 3.12 Buried BE glands with low‐grade dysplasia. This phenomenon can b...

Figure 3.13 Barrett's esophagus with high‐grade dysplasia showing p53 (left)...

Figure 3.14 Squamous low‐grade dysplasia/intraepithelial neoplasia. Note the...

Figure 3.15 (a) Squamous high‐grade dysplasia/intraepithelial neoplasia with...

Figure 3.16 Basal layer dysplasia/intraepithelial neoplasia—note the basal a...

Figure 3.17 (a) Schema of endoscopic and macroscopic classification of super...

Figure 3.18 Schematic presentation of early and superficial esophageal cance...

Figure 3.19 Well‐differentiated squamous cell carcinoma showing nests of aty...

Figure 3.20 Basaloid squamous cell carcinoma characteristically showing pleo...

Figure 3.21 Verrucous squamous cell carcinoma showing hyper‐ and parakeratos...

Figure 3.22 Sarcomatoid squamous cell carcinoma. This picture shows atypical...

Figure 3.23 Lugol's iodine staining in vivo of an early squamous cell carcin...

Figure 3.24 Endoscopic appearance of an esophageal papilloma appearing as a ...

Figure 3.25 Exophytic squamous papilloma showing delicate fibro‐vascular cor...

Figure 3.26 Gastric heterotopia “inlet patch.” The salmon‐colored mucosa is ...

Figure 3.27 Typical endoscopic image of heterotopic sebaceous glands in mid‐...

Figure 3.28 Common histomorphological appearance of “inlet patch.”

Figure 3.29 Heterotopic sebaceous glands. Note the typical vacuolated cytopl...

Figure 3.30 Glycogenic acanthosis characterized by thickening of the epithel...

Figure 3.31 Submucosal granular cell tumor showing a sharp demarcation to th...

Figure 3.32 Granular cell tumors are typically immunohistochemically positiv...

Figure 3.33 Esophageal leiomyoma (arrow) arising from the muscularis propria...

Figure 3.34 Well‐defined submucosal leiomyoma with typical whorled fascicula...

Figure 3.35 Leiomyosarcoma—fascicles of high cellularity with marked nuclear...

Figure 3.36 Kaposi sarcoma with characteristic slit‐like spaces filled with ...

Chapter 4

Figure 4.1 Endoscopic appearance of acute gastritis with superficial erosion...

Figure 4.2 HP. Gastric antral biopsy with a severe population

of Helicobacte

...

Figure 4.3 HP inflammation. H.E. stain of a punch biopsy with typical inflam...

Figure 4.4 Acute erosive changes. Antral biopsy with superficial erosion and...

Figure 4.5 Reactive gastropathy. Antral mucosa showing foveolar hyperplasia ...

Figure 4.6 (a) Focally enhanced gastritis. Gastric antral mucosa with a smal...

Figure 4.7 Autoimmune gastritis. Typical changes of mucosa of the body in th...

Figure 4.8 Lymphocytic gastritis. Superficial high magnification of a gastri...

Figure 4.9 Syphilitic gastritis. Higher magnification of a corpus biopsy sho...

Figure 4.10 High magnification of CMV gastritis with typical cherry red nucl...

Figure 4.11 Eosinophilic gastritis. Superficial biopsy of the antrum with a ...

Figure 4.12 Collagenous gastritis. Antral mucosa showing a prominent submuco...

Figure 4.13 Iron pill induced gastritis. Superficial antral mucosa with appe...

Figure 4.14 Calcifying gastritis. Antral punch biopsy with erosive and react...

Figure 4.15 Doxycycline erosive gastritis. The classic appearance is compose...

Figure 4.16 (a) GvHD. Typical changes in longstanding GvHD showing multiple ...

Figure 4.17 Chemoradiation. High magnification of a gastric mucosal biopsy w...

Figure 4.18 Kayaxylate. Example of a chronic gastric ulcer caused by Kayaxal...

Figure 4.19 GAVE. Antral mucosa with dilation changes of the capillaries and...

Figure 4.20 Amyloidosis. Superficial gastric mucosa showing dense homogenous...

Chapter 5

Figure 5.1 Single (a) or multiple (b) small translucent lesions covered by b...

Figure 5.2 Fundic gland polyposis in familial adenomatous polyposis. There a...

Figure 5.3 Low‐power photomicrograph of fundic gland polyp with multiple cys...

Figure 5.4 Higher magnification of Figure 5.3 showing cystically dilated gla...

Figure 5.5 Low‐grade (foveolar type) dysplasia in a sporadic fundic gland po...

Figure 5.6 Endoscopic appearance of a large hyperplastic polyp covered by er...

Figure 5.7 Low magnification of a hyperplastic polyp (a), showing gastric fo...

Figure 5.8 Small pyloric type glands beneath the proliferating foveolar epit...

Figure 5.9 Markedly proliferative serrated foveolar epithelium mimicking car...

Figure 5.10 Adenomatous low‐grade dysplasia found in hyperplastic polyp show...

Figure 5.11 Gastric biopsy from polypoid mass showing both hyperplastic poly...

Figure 5.12 A small polypoid foveolar hyperplasia composed solely of prolife...

Figure 5.13 Low‐power view of gastritis cystica polyposa.

Figure 5.14 Gastric biopsy specimen with bland glands admixed with edematous...

Figure 5.15 Adenocarcinoma observed in the herniated gastric mucosa in the s...

Figure 5.16 Endoscopic view of a pedunculated gastric juvenile polyp

Figure 5.17 Typical microscopic features of intestinal type adenoma with low...

Figure 5.18 Gastric foveolar type adenoma with low‐grade dysplasia (left) an...

Figure 5.19 Gastric foveolar type adenoma with pale clear cytoplasm and high...

Figure 5.20 Closely packed pyloric type glands lined by cuboidal/columnar ce...

Figure 5.21 Endoscopic appearance of a pedunculated gastric juvenile polyp w...

Figure 5.22 Cystically dilated glandular and foveolar elements in juvenile p...

Figure 5.23 Endoscopically many sessile polyps are found in patients with Pe...

Figure 5.24 Histomorphologically arborizing bundles of smooth muscles emerge...

Figure 5.25 Adenocarcinoma developed in patients with hamartomatous polyposi...

Figure 5.26 Gastric polyp in patient with Cowden's disease with foveolar hyp...

Figure 5.27 Histomorphological appearance of a biopsy from a patient diagnos...

Figure 5.28 A recently described finding in GAPPS are polyps showing hyperpr...

Figure 5.29 Inflammatory fibroid polyp presenting as broad‐based submucosal ...

Figure 5.30 Gastric biopsy specimen with proliferation of loose spindle cell...

Figure 5.31 Immunohistochemical staining of the inflammatory fibroid polyp (...

Figure 5.32 Submucosal aggregates of xanthoma cells with a distinct cell mem...

Figure 5.33 Heterotopic pancreas on the posterior wall of the mid‐body, an s...

Figure 5.34 In gastric pinch biopsies, observation of pancreatic acini in th...

Figure 5.35 Gastric pinch biopsy of a patient with endoscopical appearance o...

Chapter 6

Figure 6.1 Focal gastric neoplasia on lesser curvature of antrum shown in wh...

Figure 6.2 Intestinal/adenomatous type dysplasia. (a) Low‐grade: It shows li...

Figure 6.3 Gastric/foveolar/type 2 dysplasia. (a) Low‐grade: The lesion disp...

Figure 6.4 When a diagnosis of high‐grade dysplasia or T1 carcinoma is made ...

Figure 6.5 Well‐differentiated intramucosal adenocarcinoma. This example is ...

Figure 6.6 Well‐differentiated adenocarcinoma of tubular type. The neoplasm ...

Figure 6.7 Poorly differentiated adenocarcinoma of tubular type. It shows an...

Figure 6.8 Mucinous adenocarcinoma with limited epithelial elements noted at...

Figure 6.9 Signet ring cell gastric adenocarcinoma composed of individual si...

Figure 6.10 EBER‐positive gastric adenocarcinoma. Marked lymphocytic infiltr...

Figure 6.11 AFP‐producing gastric adenocarcinoma. Large polygonal eosinophil...

Figure 6.12 Low‐grade NET (a) showing a mixed trabecular and nested growth p...

Figure 6.13 Large cell neuroendocrine carcinoma composed of solid sheet of r...

Figure 6.14 GIST, spindle cell variant. The lesion consists of interlacing f...

Figure 6.15 GIST, epithelioid variant. The lesion shows distinctly round cel...

Figure 6.16 Microscopic aspect of gastric MALT lymphoma. (a) Low magnificati...

Figure 6.17 Gastric MALT lymphoma with plasma cell differentiation. (a) The ...

Figure 6.18 IRTA1 expression in gastric MALT lymphoma. Positive staining in ...

Figure 6.19 Control gastric biopsies after antibiotic therapy for

H. pylori

‐...

Figure 6.20 Primary gastric diffuse large B‐cell lymphoma presenting as a vo...

Figure 6.21 Diffuse large B‐cell lymphoma of the stomach. (a) Low‐power view...

Figure 6.22 Primary gastric “double‐hit” high‐grade B‐cell lymphoma with

MYC

Figure 6.23 Mantle cell lymphoma diagnosed on gastric biopsies in a 80‐year‐...

Figure 6.24 Primary gastric sporadic Burkitt lymphoma, EBV‐negative, in a 34...

Figure 6.25 Gastric involvement by an extranodal NK/T‐cell lymphoma nasal‐ty...

Chapter 7

Figure 7.1 (a) Duodenal intraepithelial lymphocytosis with normal villous ar...

Figure 7.2 Microvillous inclusion disease with vacuolization of surface epit...

Figure 7.3 Electron microscopic image characteristic of the microvillous inc...

Figure 7.4 Histologic evidence of a tufting enetropathy.

Figure 7.5 Duodenal giardiasis. Note the variable shapes of the organisms in...

Figure 7.6 Cryptosporidiosis with secondary lymphocytosis. Observe the organ...

Figure 7.7 Example of strongyloides in the duodenal crypts.

Figure 7.8 Low‐power view of MAI‐associated enteritis with diffuse histiocyt...

Figure 7.9 (a–c) Example of Whipple's disease, characterized by infiltration...

Figure 7.10 (a) Adenovirus infection with typical eosinophilic intranuclear ...

Figure 7.11 CMV duodenitis with classic CMV inclusions in endothelial cell c...

Figure 7.12 Endoscopic celiac disease with scalloping of the duodenal folds....

Figure 7.13 Example of celiac disease, Marsh grade 1 with the characteristic...

Figure 7.14 Marsh grade 3a of celiac disease with definite villous blunting....

Figure 7.15 Low‐power view of autoimmune enteropathy characterized by blunti...

Figure 7.16 Example of a tropical sprue with intraepithelial lymphocytosis a...

Figure 7.17 Collagenous sprue with obvious expansion of the lamina propria b...

Figure 7.18 Example of Crohn's ileitis with deep serpiginous ulceration, ery...

Figure 7.19 Microscopic evidence of active Crohn's ileitis (a) and granuloma...

Figure 7.20 NSAIDs enteropathy with superficial erosion and multifocal white...

Figure 7.21 Example of the Waldenstrom disease with expansion of the lamina ...

Figure 7.22 Amyloid deposition resulting in the expansion of the lamina prop...

Chapter 8

Figure 8.1 Gastric heterotopia of the proximal duodenal bulb. Note the surfa...

Figure 8.2 Gastric heterotopia. Note the surface foveolar epithelium and oxy...

Figure 8.3 Pancreatic heterotopia. In this example, the heterotopia is uniqu...

Figure 8.4 Ampullary adenomyoma. The lesion is composed of benign ductular e...

Figure 8.5 Hamartomatous polyps in a patient with Peutz–Jeghers syndrome. Th...

Figure 8.6 Intestinal pseudopolyps in a patient with inflammatory bowel dise...

Figure 8.7 Brunner's gland cyst. The lesion is located underneath the mucosa...

Figure 8.8 Juvenile polyp.

Figure 8.9 Examples of Cronkhite–Canada polyps showing a spectrum of changes...

Figure 8.10 Arteriovenous malformations detected in small bowel on capsule e...

Figure 8.11 Lymphangiectasia. Note the dilated lymphatic channels containing...

Chapter 9

Figure 9.1 Endoscopic Brunner gland adenoma in the proximal duodenum.

Figure 9.2 Brunner gland hamartoma.

Figure 9.3 Endoscopic appearance of pyloric gland adenoma.

Figure 9.4 Pyloric gland adenoma of duodenum.

Figure 9.5 Tubular adenoma of duodenum.

Figure 9.6 (a) Hyperplastic polyp of duodenum. (b) Serrated adenoma of duode...

Figure 9.7 Adenocarcinoma of intestinal type arising in neurofibromatosis wi...

Figure 9.8 Pancreatic type adenocarcinoma in ampulla.

Figure 9.9 (a) NET of the duodenum. (b) Chromogranin IHC in duodenal NET.

Figure 9.10 Endoscopic US image of GCPG. The lesion is hypoechoic (dark) ari...

Figure 9.11 (a) Gangliocytic paraganglioma H&E MP. (b) Gangliocytic paragang...

Figure 9.12 Small GIST (1–2 cm) at 1 o'clock. The lesion arises from the fou...

Figure 9.13 GIST composed of short fascicles.

Figure 9.14 Inflammatory fibroid polyp of ileum LP.

Figure 9.15 (a) Follicular lymphoma duodenum H&E. (b) Follicular lymphoma CD...

Figure 9.16 Mantle cell lymphoma ileum HP 2.

Figure 9.17 (a) Mantle cell lymphoma CD20. (b) Mantle cell lymphoma ileum CD...

Figure 9.18 Burkitt lymphoma ileum.

Figure 9.19 (a) IPSID. (b) IPSID CD138.

Figure 9.20 (a) Mastocytosis rich in eosinophils. (b) CD117 mastocytosis. (c...

Chapter 10

Figure 10.1 Biopsies of acute self‐limiting colitis (ASLC) show a preserved ...

Figure 10.2 Colonic biopsy affected by

Mycobacterium tuberculosis

showing mu...

Figure 10.3 Typical appearance of a spirochetosis of the colon showing a pur...

Figure 10.4 H.E. stain of the colon showing typical changes caused by CMV in...

Figure 10.5 Biopsy specimens of pseudomembranous colitis showing the whole s...

Figure 10.6 Example of a severe amebiasis showing a severe ulcerative coliti...

Figure 10.7 High magnification of a colon biopsy with a population of crypto...

Figure 10.8 H.E. stain of a colonic biopsy with manifestation of

Schistosoma

...

Figure 10.9 H.E. stain of Syphilitic colitis (a) with a predominant lymphopl...

Figure 10.10 Typical histological appearance of an early (a) and a late (b) ...

Figure 10.11 H.E. stain of FAC characterized by inflammation driven by neutr...

Figure 10.12 Typical finding in case of collagenous findings showing a thick...

Figure 10.13 High magnification of lymphocytic colitis characterized by an i...

Figure 10.14 Characteristic changes in colonic biopsies caused by mucosal pr...

Figure 10.15 High magnification of a colonic biopsy with changes characteris...

Figure 10.16 Example of mastocytic colitis showing a slightly increased mixe...

Figure 10.17 Mycrophenolate mofetil‐related colitis is a pitfall mimicking c...

Figure 10.18 Endoscopic appearance of severe Crohn's disease. (a) Deep ulcer...

Figure 10.19 Endoscopic appearances of ulcerative colitis: (a) severe ulcera...

Figure 10.20 Colonic mucosa with typical architectural disarray caused by UC...

Figure 10.21 Colonic mucosa of UC showing a dense lymphoplasmacytic infiltra...

Figure 10.22 Typical inflammatory changes of an active UC showing crypt absc...

Figure 10.23 Specimen of a long‐standing UC under therapy showing scattered ...

Figure 10.24 Hisological appearance of a Crohn's patient showing a dense inf...

Figure 10.25 Small epithelioid granuloma found in the lamina propria of a co...

Figure 10.26 Low‐grade IBD‐associated dysplasia. This lesion shows a convent...

Figure 10.27 High‐grade IBD‐associated dysplasia shows crowded, focally back...

Figure 10.28 Hypermucinous dysplasia typically shows a villous/tubulovillous...

Figure 10.29 IBD‐associated TSA‐like dysplasia presents with narrow, slit‐li...

Figure 10.30 Example of goblet cell‐deficient dysplasia (GCD) with tubular c...

Chapter 11

Figure 11.1 Tubulovillous adenoma with high‐grade dysplasia. Features sugges...

Figure 11.2 Paris Classification of polyp shape. 0–1p refers to pedunculated...

Figure 11.3

Narrow‐band imaging International Classification for Endoscopy

...

Figure 11.4 Hematoxylin–Eosin stain of a tubulovillous adenoma with high‐gra...

Figure 11.5 Endoscopic resection of sessile serrated polyp (a) with standard...

Figure 11.6 Hyperplastic polyp as seen in narrow‐band imaging model. Note th...

Figure 11.7 Hyperplastic polyp presenting as a localized projection of the c...

Figure 11.8 Sessile serrated lesion displaying horizontally shaped crypt bas...

Figure 11.9 Sessile serrated lesion with dysplasia. This lesion was atypical...

Figure 11.10 Sessile serrated lesion with dysplasia. There is a clear demarc...

Figure 11.11 Endoscopic appearance of a rectal polyp being diagnosed as a trad...

Figure 11.12 Traditional serrated adenoma with villous projections, ectopic ...

Figure 11.13 Endoscopic examples of (a) inflammatory and (b) filiform pseudo...

Figure 11.14 Typical histomorphology of a juvenile polyp with haphazardly cy...

Figure 11.15 Hamartomatous polyp in a patient with Peutz–Jeghers syndrome ch...

Figure 11.16 Microscopic appearance of a colonic mucosal leiomyoma with its ...

Figure 11.17 Histology of a submucosal lipoma with benign well‐circumscribed...

Figure 11.18 Endoscopic ultrasound (EUS) image of a lipoma arising in the su...

Figure 11.19 Combined fibroblastic polyp and SSL with fibrotic changes of th...

Figure 11.20 Colonic polyp with collagen bundles and thick eosinophilic elas...

Figure 11.21 Colonic polypoid endometriosis with its typical glands being su...

Chapter 12

Figure 12.1 Cecal polyp showing invasion of the lamina propria by small atyp...

Figure 12.2 Various macroscopic appearances of colorectal carcinoma presenti...

Figure 12.3 Medullary carcinoma of the proximal colon consisting of sheets o...

Figure 12.4 Loss of immunohistochemical expression of MLH1 in a medullary ca...

Figure 12.5 Metastatic melanoma in the sigmoid colon: infiltration of the co...

Figure 12.6 Endometriosis presenting as a large mass in the upper rectum, mi...

Figure 12.7 Endometriosis in the rectal mucosa: Endometrial glands surrounde...

Figure 12.8 (a) Endoscopical appearance of malignant sessile colon polyp wit...

Figure 12.9 Pseudoinvasion in the stalk of a large pedunculated tubular aden...

Figure 12.10 NET of the rectum showing an anastomosing ribbon pattern infilt...

Figures 12.11 and 12.12 Large cell neuroendocrine carcinoma of the rectum sh...

Figures 12.13 and 12.14 Endoscopic appearance of mucosal‐associated lymphoid...

Chapter 13

Figure 13.1 Example of anal fissure lined by inflamed granulation tissue and...

Figure 13.2 (a) Large external hemorrhoid seen via anoscopy. A snare device ...

Figure 13.3 Anal involvement by Crohn's disease with granulomatous inflammat...

Figure 13.4 (a) Syphilis proctitis: Cryptitis and expanded lamina propria in...

Figure 13.5 (a) Columnar mucosa with expanded lamina propria inflammatory in...

Chapter 14

Figure 14.1 (a) Inflammatory cloacogenic polyp: The polyp is composed of elo...

Figure 14.2 Fibroepithelial polyp: The polyp has a core containing variably ...

Figure 14.3 (a) Hidradenoma papilliferum: A submucosal proliferation of papi...

Figure 14.4 Squamous hyperplasia: The squamous mucosa has acanthosis (thicke...

Figure 14.5 (a) Condyloma acuminatum: There is acanthosis of the squamous mu...

Figure 14.6 Anal intraepithelial neoplasia grade 1/low‐grade squamous intrae...

Figure 14.7 Anal intraepithelial neoplasia grade 3/high‐grade squamous intra...

Figure 14.8 (a) Perianal Paget's disease: Paget's cells are scattered throug...

Figure 14.9 Endoscopic view of anal squamous cell carcinoma at the 6 o'clock...

Figure 14.10 (a) Invasive squamous cell carcinoma, keratinizing, with infilt...

Figure 14.11 Malignant melanoma: Panel A shows a densely cellular lesion adj...

Guide

Cover Page

Title Page

Copyright Page

List of Contributors

Table of Contents

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Index

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Gastrointestinal Pathology

Correlative Endoscopic and Histologic Assessment

Edited by

Gregory Y. Lauwers, MD, FAGPS

Senior Member and Director, Gastrointestinal Pathology Service

Department of Pathology, Moffitt Cancer Center

Professor, Departments of Pathology and Cell Biology and Oncologic Sciences

University of South Florida

Tampa, FL, USA

Michael B. Wallace, MD, MPH

Consultant – Gastroenterology and Hepatology

Fred C. Andersen Professor of Medicine, Mayo Clinic School of Medicine

Jacksonville, FL, USA

Associate Editor:

Till S. Clauditz, MD

Associate Professor, Head of Gastrointestinal Pathology Service

Department of Pathology with Section Molecular Pathology and Cytology

University Medical Center Hamburg‐Eppendorf,

Hamburg, Germany

This edition first published 2021© 2021 John Wiley & Sons Ltd

All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by law. Advice on how to obtain permission to reuse material from this title is available at http://www.wiley.com/go/permissions.

The right of Gregory Y. Lauwers and Michael B Wallace to be identified as the authors of the editorial material in this work has been asserted in accordance with law.

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Cover Design: WileyCover Images: © Gregory Y. Lauwers and Michael B. Wallace

List of Contributors

Thomas ArnasonQueen Elizabeth II Health Sciences Centre and Dalhousie UniversityHalifaxNova ScotiaCanada

Ian BrownEnvoi Specialist PathologistsBrisbaneAustralia

Till S. ClauditzDepartment of PathologyUniversity‐Medical‐CenterHamburgGermany

Tze Sheng KhorPathWest Laboratory MedicineQueen Elizabeth II Medical CentreNedlandsWestern AustraliaAustralia

K. KimSamsung Medical CenterSungkyunkwan University School of MedicineSeoulSouth Korea

Bence KőváriDepartment of PathologyUniversity of SzegedSzegedHungary

Priyanthi KumarasingheDepartment of Anatomical PathologyPathWest, QE II Medical CentreUniv. of Western AustraliaPerthAustralia

Gregory Y. LauwersMoffitt Cancer CenterTampaFloridaUSA

Jun Haeng LeeSamsung Medical CenterSungkyunkwan University School of MedicineSeoulSouth Korea

Laurence de LevalInstitute of PathologyUniversity of LausanneLausanneSwitzerland

Anthony R. MattiaNewton‐Wellesley HospitalNewton, MAUSA

Christophe RostyEnvoi Specialist PathologistsBrisbaneQueenslandAustralia

Yutaka SaitoNational Cancer CenterTokyo Japan

Mounir TrimecheInstitute of PathologyUniversity of LausanneLausanneSwitzerland

Michael B. WallaceMayo ClinicJacksonvilleFloridaUSA

Herbert C. WolfenMayo Clinic Jacksonville Florida USA

Naohisa YahaghiKeio University Cancer CenterTokyoJapan

1General Principles of Biopsy Diagnosis of GI Disorders

Herbert C. Wolfen1, Michael B. Wallace1, Naohisa Yahaghi2 and Yutaka Saito3

1 Mayo Clinic, Jacksonville, Florida, USA

2 Keio University Cancer Center, Tokyo, Japan

3 National Cancer Center, Tokyo Japan

Tissue sampling of the gastrointestinal tract at the time of endoscopy is the cornerstone of many gastrointestinal diagnoses. The development of a flexible endoscope and the subsequent ability to directly acquire tissue under optical guidance has been one of the most important advancements in the field of gastroenterology throughout its history. Although tissue sampling can be performed through nonendoscopic devices, the ability to directly correlate precise locations and target biopsies to specific areas of disease is critical to our ability to diagnose and further understand gastrointestinal pathology. Many of the advancements in our understanding of the basic pathology and molecular biology of gastrointestinal disease can be directly attributed to our ability to acquire tissue for histological, molecular, and genetic analyses. An excellent example is our deep understanding of the molecular pathology of colorectal cancer development from normal colonic epithelium to adenoma to colorectal cancer, a discovery made possible because of colonoscopic access to precursor lesions such as adenomatous polyps and early cancers.

In this chapter, we will review general principles of tissue acquisition at the time of endoscopy including the following topics:

Endoscopic equipment for obtaining tissue including endoscopic accessory channels, biopsy forceps, snare devices, needle aspiration and cytology brush.

General principles of optimal sampling technique.

Methods of tissue preparation in the endoscopy laboratory to optimize diagnostic accuracy.

The role of endoscopic ultrasound (EUS)‐guided fine‐needle aspiration cytology.

Endoscopic Equipment for Tissue Sampling

Modern endoscopic equipment can be divided in two general categories: the endoscope that allows access to the gastrointestinal tract and accessory devices that are typically passed through the working channel of the endoscope to directly acquire tissue, including biopsy forceps, snares, fine‐needle aspiration devices, and cytology brushes. Recent developments in tissue sampling include devices that are capable of wide‐field, often definitive, endoscopic resection of early neoplasia and invasive carcinoma.

A modern endoscope is a remarkably robust and versatile instrument including a light source, optical lenses with a video capture device, image processing, and display equipment, and importantly for the purposes of tissue acquisition, an accessory channel ranging from 1 to 6 mm (typically 3–4 mm), which allows passage of devices for mechanical collection of tissue (Figures 1.1 and 1.2).

There is a general trade‐off between the diameter of the instrument and the ease and comfort with which it can be passed through the natural orifices of the body such as the mouth and anus. In general the larger the outer diameter, the larger the accessory channel is to accommodate larger instruments for tissue acquisition. A fundamental limitation of most flexible endoscopes, as opposed to surgical instruments, is that all accessories pass through a single access point of the endoscope. As compared to surgical instruments with multiple access points, the endoscopic devices do not typically allow triangulation to acquire a large bulk tissue or resect entire organs. For this reason, most tissue is sampled through pinch forceps, needle aspiration, or wire loop snare devices. More recently, electrosurgical needles and other cutting tools have been developed, which have allowed wide‐field resection of tissues of virtually any diameter (Figure 1.3).

Figure 1.1 Endoscope with control handle and tip. The tip contains a light source, imaging window, and accessory channel through which various tissue acquisition devices can be passed.

Figure 1.2 Endoscopic processor, which converts the light captured from the endoscope tip into a visible image for display.

Source: Olympus America, Inc. With permission.

Figure 1.3 (a) Tools for performing endoscopic resection including endoscopic submucosal dissection (ESD).

Source: Zeon Medical.

(b) Standard and insulated tip electrocautery knives for incision and dissection.

Source: © 2017 Korean Society of Gastrointestinal Endoscopy.

(c) CO2 insufflator for luminal distension, which is preferred to air given rapid reabsorption.

Source: Olympus.

(d) Distal attachment hood to facilitate maintaining view within the submucosal space.

Source: Fujifilm medical.

(e) Injection fluid (hyaluronic acid; Mucoup [Johnson and Johnson]) for submucosal lifting.

Source: Gut and Liver.

Pinch Biopsy Forceps

The flexible pinch biopsy forceps have been one of the most versatile of all instruments for tissue acquisition. These typically involve a flexible steel cable and lever device with two sharp‐edged cups, which can be opened and closed to acquire tissue (Figure 1.4).

Standard endoscopic sampling typically acquires tissue from the mucosa and occasionally a submucosal depth of the intestinal wall; however, large‐capacity forceps as well as multiple sampling including “bite on bite” allow sampling of the deeper layers. Pinch biopsy forceps come in multiple sizes from very small instruments such as a pediatric forceps, which can be passed through very small working channels. Recent development of very tiny forceps makes it possible to pass them through special endoscopes into the bile or pancreas duct and to pinch biopsy outside of the traditional gastrointestinal lumen (Figure 1.5).

Studies comparing jumbo forceps to standard forceps have generally not shown significant advantages of larger capacity forceps. A limitation of most forceps is the inability to sample tissue in the submucosa routinely. This is highlighted in studies looking for Barrett's esophagus after the surface epithelium has been ablated. Biopsy forceps can remove tissue with mechanical closure alone or with electrocautery (“hot biopsy”) although the use of hot biopsy has diminished significantly due to increased risks of complication and tissue damage in the biopsy specimen.

Figure 1.4 Endoscopic biopsy forceps in the open position. The needle‐like pin in the center holds the tissue in place so one to two samples can be obtained per pass.

Figure 1.5 Micro biopsy forceps <1 mm in diameter, which can be passed through specialized endoscopes into the bile duct, pancreas duct, or via 19‐gauge needles for extraluminal tissue sampling.

Source: Boston Scientific Corporation with permission.

Figure 1.6 Endoscopic snare for polypectomy. The wire loop is extended in the open position outside the plastic sheath. When closed, the wire loop is strangulated and resects the polyp tissue.

Figure 1.7 Endoscopic cytology brush. Note the abrasive brush extended beyond the protective plastic sheath.

Endoscopic Snare Devices

Endoscopic snare devices have also been widely used for resection of polypoid as well as flat lesions throughout the gastrointestinal tract. They have been remarkably versatile and effective over the past four decades. Endoscopic snares typically involve a metallic wire, which may braided or monofilament (Figure 1.6).

A wire loop is generally constrained within a small caliber plastic catheter. At the distal end of the catheter, the wire loop can be opened to various sizes to grasp and resect polyps of different sizes. Typical sizes include loops 5–30 mm in diameter. There are numerous different shapes including oval, hexagonal, and asymmetric “duck bill.” Snares also come in various degrees of stiffness, which allow resection of lesions of many shapes and sizes. Tissue can be resected with mechanical closure alone (so‐called “cold snare”) or with mechanical plus electrosurgical cutting (“hot snare”). Recent studies suggest that cold snare is associated with lower risk of bleeding and bowel wall injury.

Endoscopic Brush Cytology

Abrasive brush cytology has been used in many different fields of tissue sampling. Typical endoscopic brush is constrained within a plastic catheter similar to endoscopic snares (Figure 1.7).

After passing through the accessory channel of the endoscope, the abrasive brush is exposed and rubbed against the area of tissue sampling. This is most commonly applied to obtain specimens for microbiology, particularly fungal specimens. These have also been widely applied in the biliary tract for sampling of suspicious biliary strictures. More recent advances include a highly abrasive wide‐area tissue sampling system that has been recently studied and Barrett's esophagus as an alternative to pinch forceps, as well as nonendoscopic abrasive sponge sampling, which has the potential to offer inexpensive population‐based screening for esophageal neoplasia (Figure 1.8).

Figure 1.8 Nonendoscopic abrasive cytology brush.

Source: From Kadri, S.R., Lao‐Sirieix, P., O'Donovan, M. et al. (2010). Acceptability and accuracy of a non‐endoscopic screening test for Barrett's oesophagus in primary care: cohort study. BMJ341: c4372. doi: https://doi.org/10.1136/bmj.c4372. Open access article.

Endoscopic Fine‐Needle Aspiration (FNA) Devices

The most common application of FNA devices in endoscopy is endoscopic ultrasound‐guided tissue sampling (EUS‐FNA). The development of endoscopic ultrasound in the 1970s and 1980s significantly expanded the reach of endoscopic tissue sampling into the pancreas and other extraluminal organs such as lymph nodes and now virtually any organ within reach of the proximal or distal GI tract lumen (Figure 1.9).

Other needle aspiration devices include biliary sampling needles often used in conjunction with forceps and brush sampling, or so‐called “triple sampling.” EUS‐FNA devices come in various sizes from 19‐ to 25‐gauge. These devices are typically attached to a handle, which allows the endoscopist to puncture and make to‐and‐fro movements within the target lesion and also apply negative pressure. With various methods, both cytologic and histologic material can be obtained through these needle devices. Recent efforts to develop Tru‐Cut devices have been met with variable success.

Tissue Processing in the Endoscopy Laboratory

An excellent recent review on the topic of tissue acquisition has been published by the American Society for gastrointestinal endoscopy. For most routine tissue sampling the biopsy material is placed in formalin and subsequently embedded in paraffin for histological analysis. Other specific preparations include sampling for microbiological evaluation, molecular or genetic testing, and electromicroscopy. These special samples should be handled according to local institutional guidelines. In general, samples that are obtained for culture should be obtained prior to placing forceps into formalin as formalin residue can destroy or inactivate live microbial tissue.

Figure 1.9 (a) and (b) Endoscopic ultrasound endoscope and guided fine‐needle aspiration (EUS‐FNA) device.

Non‐oriented Samples

Most pinch biopsy samples are placed directly in formalin without orientation. This is also true for small polyps where the likelihood of invasive cancer is very low. The sample is placed directly into a small formalin jar. The needle or forceps should be rinsed if it comes in direct contact with formalin as subsequent contact with living tissue can cause chemical injury.

Oriented Samples

Increasingly, endoscopic resection is being used for definitive oncologic removal of precancerous and invasive lesions. In these cases it is advantageous to orient the specimen so that precise staging as well as margin assessment can be performed. A typical situation is in endoscopic resection of early neoplasia in the esophagus such as Barrett's esophagus. In this case a sample is frequently obtained through endoscopic mucosal resection. Large pieces of tissue, typically 1–2 cm in diameter, can be obtained to a depth of the submucosa. In this case the sample should be removed from the patient in a way that does not damage or distort the tissue. This is typically performed by suctioning the tissue into a distal attachment cap/hood and then removing the endoscope. Alternative retrieval devices include a modified snare with a protective net. These tissues should then be immediately oriented at the bedside typically by placing them on a paraffin or similar firm block. The tissue should be flattened typically with the mucosal side up and the edges carefully pinned so that the tissue remains flat (Figure 1.10).

Cytology Samples

Cytology samples obtained from either brush or fine‐needle aspiration can be processed in a variety of ways. Most commonly these are prepared as thin smear on glass slides, which can be evaluated either immediately as an air‐dried sample stained with a modified Romanowsky stain, or as an alcohol‐fixed slide evaluated with Papanicolaou staining. It is often helpful to place additional excess material in a cytological preservative or formalin. Special handling is required for samples where lymphoproliferative disease is considered. Typically these include cytological preservatives such as Roswell Park Memorial Institute (RPMI) medium that allow subsequent flow cytometry. As a practical matter, placement in such a preservative should be considered even when likelihood is low since cells preserved in such solution can always be examined with routine cytological methods; however, cells that are placed in formalin or alcohol cannot be evaluated for flow cytometry. The use of rapid on‐site evaluation (ROSE) cytology has been shown in many studies to increase diagnostic yield and reduce the need for repeated procedures.

Figure 1.10 Pinned and oriented resection tissue from Barrett's esophagus‐associated neoplasia. Note the mucosal side facing up and the lateral margins pinned to prevent curling of the edges.

Culture Samples

Samples obtained for culture should be placed in a sterile specimen container. Sterile saline maybe needed to prevent drying of the specimen. Attention should be paid to minimize contamination although it is recognized that the endoscope and the organs throughout which it is passed are not sterile and is not possible to obtain a purely sterile access into the gastrointestinal lumen. Contamination with oropharyngeal organisms or colonic organisms is not uncommon.

Specific Organ Sampling Methods

Esophagus

Diagnostic Sampling

Indications for diagnostic sampling of the esophagus include Barrett's esophagus and other suspected neoplastic disorders, inflammatory disorder such as eosinophilic esophagitis, gastroesophageal reflux disease, and infectious esophagitis.

The most common indication in Western countries for tissue sampling from the esophagus is likely Barrett's esophagus. There are established guidelines for sampling of the esophagus. These have traditionally been based on the notion that early neoplasia is not visible endoscopically and thus random sampling of the mucosa should be performed to ensure adequate detection of early neoplasia. The most widely used standard is the so‐called Seattle protocol. The American Society for Gastrointestinal Endoscopy (ASGE) guideline for tissue sampling calls for surveillance of nondysplastic Barrett's esophagus in four quadrants every 2 cm with a large‐capacity forceps for the entire Barrett's mucosa. Patients with established low‐grade dysplasia sampling should be more intensive with four‐quadrant biopsies every 1–2 cm. For patients who choose to undergo surveillance for high‐grade dysplasia, sampling every 1 cm should be performed; however, more recent evidence suggests that patients with established low‐grade and high‐grade dysplasia should likely undergo therapy to eradicate the Barrett's esophagus. Advances in endoscopic imaging, such as high‐definition narrow‐band imaging, confocal laser endomicroscopy, and chromoendoscopy, have significantly increased the yield of biopsy and allow much more targeted sampling although these have not yet replaced the need for random biopsy. These advances are likely to reduce the need for random biopsies and focus more on targeted sampling.

For eosinophilic esophagitis the ASGE recommends two to four biopsies from the proximal esophagus and two to four biopsies from the distal esophagus. Biopsy should also be obtained from the gastric antrum and duodenum when diffuse eosinophilic gastroenteritis is suspected.

For suspected infectious esophagitis, multiple biopsies from the margin and base of a visualized ulcer should be obtained and the sample should be sent for standard histology as well as immunohistochemical and possibly viral cultures and PCR. For candidal esophagitis, multiple biopsies of the affected area as well as cytology brushings may be complementary to biopsy.

Therapeutic Sampling

Increasingly, endoscopic resection methods are being applied to early neoplasia the esophagus, particularly Barrett's esophagus and early squamous cell carcinoma. These are largely confined to tumors suspected to be T1 or nodular high‐grade dysplasia. Endoscopic mucosal resection (EMR) methods generally involve an EMR device such as a modified band ligator followed by snare resection of the pseudopolyp (Figure 1.11–1.13).

Other methods include endoscopic submucosal dissection (ESD) in which the lateral margins of the suspected area are incised with electrocautery knife followed by dissection along the submucosal plane to obtain an en bloc specimen. EMR devices can typically obtain samples 1–2 cm in diameter into the depth of the mid‐submucosa. Endoscopic submucosal dissection can obtain samples of any lateral diameter and generally to the base of the submucosa.

Figure 1.11 Barrett's esophagus with flat neoplasia (9 o'clock) for targeted endoscopic resection.

Figure 1.12 Multiband mucosectomy device. The black rubber bands are mounted on the outside of a plastic cap. The tissue is suctioned into the cap and a band deployed to create a pseudopolyp, which is then removed by snare.

Figure 1.13 Area of resection at 6–12 o'clock includes the entire region of suspected neoplasia at 9 o'clock. The remaining tissue at the 9 o'clock area represents intact deep submucosa and muscularis propria.

One major advantage of these techniques is the ability to perform wide‐field or en bloc resection and orient the sample. Samples should be retrieved without causing trauma to the tissue, preferably by removal through the endoscopic cap or through a snare‐net as opposed to suctioning via the accessory channel, which can traumatize or fragment the tissue. Once retrieved the tissue should be handled as with other endoscopic resection specimens by orienting the specimen and pinning it on a fixed material such as a paraffin block. En bloc specimens can be oriented in terms of the oral and anal side of the lesion and assessed for lateral and deep margins. For resections that are performed piecemeal such as with multiband mucosectomy, the lateral margins cannot be accurately assessed and so complete resection relies on the endoscopic inspection intraluminally. The specimens should still be oriented and assessed for the deep margin.

Stomach

Diagnostic Sampling

Major indications for diagnostic sampling of the stomach include assessment for Helicobacter pylori infection, diagnosis of gastritis, metaplastic atrophic change, gastric polyps, and suspected neoplasia, particularly in the setting of gastric ulceration or early gastric cancer.

H. pylori Sampling

Biopsy is one of several recommended methods for H. pylori sampling that also includes urease breath testing and stool testing for H. pylori