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Introduction to the GIT system Pathology lecture: 1 Dr. Dua Abuquteish, MBBS

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Page 1: Introduction to the GIT system

Introduction to the GIT system

Pathology lecture: 1

Dr. Dua Abuquteish, MBBS

Page 2: Introduction to the GIT system

MBBS: J.U.S.T/ Jordan

Pathology Residency: K.A.U.H / Jordan

▪Gastrointestinal / liver pathology clinical fellowship: University of Toronto/ Canada

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Notes about the GIT system

Coordinator: Dr. Dua Abuquteish

Contact email: [email protected]

My room: 1020

The GIT system has 61 lectures

15 are pathology lectures

Pathology labs will include the images from the lectures (TBD).

Two theory exams (40% each) and one practical 20%, all the exams will be at the end of the system

For more details regarding the system, please refer to your syllabus

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Questions

For questions and inquiries:

▪Ask direct in the lecture

▪Or please email me

[email protected]

Please specify in the email subject (Question; lecture # or lecture title)

▪Do NOT chat the question on Microsoft teams

▪Please feel free to come to my office #1020

Page 5: Introduction to the GIT system

From where to study pathology and what’s included in the exam?

Slides

Book (Robbins Basic

Pathology, 10th edition)

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I did NOT give consent for video recording Thus, you will be subject to legal liability

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Let’s start!

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What does the GIT system include?

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How does the digestive system work?

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The most common symptoms of gastrointestinal diseases

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How are the patients with GIT symptoms diagnosed?

History taking

Clinical inspection

Lab test (CBC, LFT, Fecal occult blood in stool; FOBT)

Imaging (abdominal ultrasound, MRCP, ERCP, barium enema)

Non-surgical procedures: upper and lower endoscopy (colonoscopy)

Surgical procedures (laparoscopy or laparotomy)

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The fecal occult blood test (FOBT) is a lab test used to check stool samples for hidden (occult) blood

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Barium enema

A barium enema is a radiographic (X-ray) examination of the lower gastrointestinal (GI) tract.

The large intestine, including the rectum, is made visible on X-ray film by filling the colon with a liquid suspension called barium sulfate (barium).

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Upper endoscopy: Is a nonsurgical procedure used to examine a person's digestive tract. Using an endoscope, a flexible tube with a light and camera attached to it, your doctor can view pictures of your digestive tract on a color TV monitor.

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Upper endoscopy

Tissue samples (biopsies) can be taken during endoscopy.

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Colonoscopy (lower endoscopy): Is a long, flexible tube (colonoscope) that is inserted into the rectum. A tiny video camera at the tip of the tube allows the doctor to view the inside of the entire colon.

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Colonoscopy

Tissue samples (biopsies) can be taken during colonoscopy

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Laparoscopy

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Laparotomy(open surgery)

Is a surgical incision (cut) into the abdominal cavity

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What is the role of pathology in diagnosing patients?

The pathologist receives biopsies and specimensthat are obtained from surgical and non-surgical procedures:

Non-surgical procedures: Upper and lower endoscopy (colonoscopy)

Surgical procedures (laparoscopy or laparotomy)

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Specimens go to pathology lab

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Steps in Biopsy processing

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Grossing

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Processing and Hematoxylin and eosin stainingH&E

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Reporting

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Example of a final pathology report

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Example of a final pathology report

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Immunohistochemistry

Sometimes stains, other than H&E, are used to confirm the

diagnosis.

Immunohistochemistry (IHC) is a technique that uses antibodies conjugated to enzymes that catalyze reactions to form detectable compounds to visualize and localize specific antigens in a tissue sample.

H&E: CMV inclusions

Immunohistochemistry: CMV inclusions

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ORAL CAVITY

Diseases affecting teeth their support structures, oral mucosa, salivary glands, and jaws.

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DISEASES OF TEETH AND SUPPORTING STRUCTURES

Dental Carries

Gingivitis

Periodontitis

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Dental Carries

Most common cause of tooth loss in individuals younger than 35 years of age.

Caries results from focal demineralization of tooth structure (enamel and dentin) caused by acids generated during the fermentation of sugars by bacteria.

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Gingivitis

Gingivitis is inflammation involving the squamous mucosa and associated soft tissues that surrounds the teeth.

It is associated with buildup of dental plaque and calculus

Associated with poor oral hygiene

Chronic gingivitis shows gingival erythema, edema, and bleeding.

Gingivitis is reversible, primarily by regular brushing and flossing of teeth

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Periodontitis

Periodontitis is a chronic inflammatory condition

that can lead to the destruction of the supporting

structures of the teeth.

With progression, periodontitis may result in

destruction of periodontal ligament and alveolar

bone and eventual tooth loss.

It is associated with poor oral hygiene and altered

oral microbiota.

Page 34: Introduction to the GIT system

ORAL INFLAMMATORY

LESIONS

Aphthous Ulcers (Canker Sores)

Herpes Simplex Virus Infections

Oral Candidiasis (Thrush)

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Aphthous Ulcers (Canker Sores)

Up to 40% of population (very common!)

More frequent in the first 2 decades of life

Extremely painful, and often recur

Unknown etiology (?viruses, hypersensitivity)

Triggered by stress, fever, menstruation, pregnancy, certain foods; may be familial

May be associated with inflammatory bowel disease & Behcet syndrome

Self limiting in a few weeks, but can recur

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Aphthous Ulcers (Canker Sores)

Solitary or multiple; typically, they are shallow, with a hyperemic base covered by a thin exudate and rimmed by a narrow zone of erythema, usually <1 cm, may coalesce

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Herpes Simplex Virus

(HSV) Infections

“Herpetic stomatitis”

Most orofacial herpetic infections are HSV-1, with the

remainder being HSV-2 (genital herpes)

Person to person transmission

Patients presents with vesicles (cold sores, fever

blisters) that rupture and heal, without scarring, and

often leave latent virus in nerve ganglia.

Primary infection is self limited. Reactivation occurs

when there is a compromise in host resistance.

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Herpes Simplex Virus (HSV) Infections“Herpetic stomatitis”

Primary infections typically in children (2 to

4 years) and are often asymptomatic.

However, 10% to 20% manifests as acute

herpetic gingivostomatitis (abrupt onset of

vesicles and ulcerations throughout the oral cavity).

Acute herpetic gingivostomatitis

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After primary infection virus will persist in ganglia in dormant state

In adulthood, the virus can be reactivated, resulting in a so-called “cold sore” or “recurrent herpetic stomatitis”.

Reactivation: fever, sun or cold exposure, URTI, ..

Most common locations involved: the lips (herpes labialis), nasal orifices, buccal mucosa, gingiva, and hard palate.

Self limiting in a few weeks, but can recur

They can persist in immunocompromised patients, who may require systemic anti-viral therapy.

Herpes Simplex Virus

(HSV) Infections

“Herpetic stomatitis”

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Herpes Simplex Virus (HSV) Infections

“Herpetic stomatitis”

The infected cells become ballooned and have large eosinophilic intranuclear inclusions.

Adjacent cells commonly fuse to form large multinucleated polykaryons.

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Oral Candidiasis (Thrush)

Candidiasis is the most common fungal infection of the oral cavity.

Candida albicans is a normal component of the oral flora.

However, can produce disease when the oral microbiota is altered

(e.g., after antibiotic use) and in immunosuppression

Invasive disease may occur in severe immunosuppressed

individuals.

Three major clinical forms of oral candidiasis are:

1. Pseudomembranous (most common and is known as thrush)

2. Erythematous

3. Hyperplastic

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Oral Candidiasis (Thrush)

❑ Superficial, curdlike, gray to white inflammatory membrane composed of matted organisms.

❑This layer can be readily scraped off to reveal an underlying erythematous base.

Densely matted pseudohyphae and budding spores

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PROLIFERATIVE AND

NEOPLASTIC LESIONS OF

THEORAL CAVITY

▪Fibrous Proliferative Lesions

(Fibromas and pyogenic granuloma)

▪Leukoplakia and Erythroplakia

▪Squamous Cell Carcinoma

Page 44: Introduction to the GIT system

Fibromas

Submucosal nodular fibrous tissue masses that are formed when chronic irritation results in reactive connective tissue hyperplasia.

They occur most often on the buccal mucosa along the bite line.

Treatment: complete surgical excision and removal of the source of irritation.

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Pyogenic granuloma

An inflammatory lesion typically found on the gingiva of children, young adults, and pregnant women (pregnancy tumor).

Complete surgical excision is definitive treatment.

These lesions are richly vascular and typically ulcerated, which gives them a red to purple color. In some cases, growth can be rapid and raise fear of a malignant neoplasm.

Histologically: Proliferation of immature vessels like that seen in granulation tissue

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Leukoplakia and

Erythroplakia

Leukoplakia: is a white patch or plaque that cannot be

scraped off and cannot be characterized clinically or

pathologically as any other disease.

White patches caused by obvious irritation or entities such

as candidiasis are NOT considered leukoplakia.

5% to 25% are dysplastic and at risk for progression to

squamous cell carcinoma.

Thus, until proved otherwise, all leukoplakias must be

considered precancerous.

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Leukoplakia

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Erythroplakia

Erythroplakia, less common entity, is a red, velvety,

sometimes eroded lesion that is flat or slightly depressed

relative to the surrounding mucosa.

Erythroplakia is associated with a much greater risk for

malignant transformation than leukoplakia (up to 50%).

Leukoplakia and erythroplakia, the usual age (40 - 70 years)

Tobacco use (cigarettes, pipes, cigars, and chewing tobacco)

is the most common risk factor for leukoplakia and

erythroplakia.

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Erythroplakia

Red, velvety, sometimes eroded lesion that is flat or slightly depressed

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Leukoplakia

On histologic examination

leukoplakia and erythroplakia

show a spectrum of epithelial changes ranging from hyperkeratosis, acanthothosis, to markedly dysplasia and sometimes merging into carcinoma in situ

Normal squamous

mucosa

Note the sharp demarcation between normal and leukoplakia. Leukoplakia shows acanthosis and hyperkeratosis. No epithelial atypia.

Leukoplakia

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Example of erythroplakia with squamous epithelial atypia (dysplasia)

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Squamous Cell Carcinoma

SCC

95% of the oral cavity cancers are SCC

Most common locations are: ventral surface of

the tongue, floor of the mouth, lower lip, soft

palate, and gingiva

Survival rate < 50% for the past 50 years

(diagnosed at advanced stage).

Page 54: Introduction to the GIT system

Squamous Cell Carcinoma

SCC

Pathogenesis

SCC of oropharynx arise through two distinct pathogenic pathways:

1. Exposure to carcinogens (chronic alcohol and tobacco, betel quid and paan), mutations frequently involve TP53 and genes that regulate cell proliferation, such as RAS

2. Infection with high-risk variants of human papilloma virus (HPV).

Page 55: Introduction to the GIT system

HPV-related tumors tend to occur in the tonsillar crypts

or the base of the tongue and harbor oncogenic “high-

risk” subtypes, particularly HPV-16.

HPV-related tumors have fewer mutations; often

overexpress p16

The prognosis for patients with HPV-positive tumors is

better than for those with HPV-negative tumors.

Squamous Cell Carcinoma

SCC

Page 56: Introduction to the GIT system

Squamous Cell Carcinoma

SCC

➢Marked atypical tumor cells with invasion and islands that show formation of keratin pearls

➢May be superimposed on a background of leukoplakia or erythroplakia

keratin pearls

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Squamous Cell Carcinoma

SCC

Typically, oral squamous cell carcinoma infiltrates locally before it metastasizes.

The cervical lymph nodes are the most common sites of regional metastasis; frequent sites of distant metastases include the mediastinal lymph nodes, lungs, and liver.

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Diseases of Salivary glands

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Diseases of Salivary glands

Three major salivary glands:

❑Parotid

❑Submandibular

❑Sublingual

—as well as innumerable minor salivary glands distributed throughout the oral mucosa.

Diseases of salivary glands include:

Inflammation

Neoplasms (Benign and Malignant)

Page 61: Introduction to the GIT system

Diseases of Salivary glands

Xerostomia

Xerostomia is defined as a dry mouth resulting from a decrease in the production of saliva.

Causes:

Part of autoimmune disorder Sjögren syndrome; also accompanied by dry eyes.

Complication of radiation therapy.

Medications such as: anti-cholinergic, anti-depressant/ anti-psychotic, diuretic, anti-hypertensive, sedative, muscle relaxant, analgesic, and anti-histaminic agents.

Page 62: Introduction to the GIT system

Diseases of Salivary glands

Sjogren's syndrome An autoimmune disease, in which the immune system attacks the exocrine glands (glands that make tears and saliva). This causes a dry mouth (Xerostomia) and dry eyes (Xerophthalmia)

Xerostomia

The oral cavity may reveal only dry mucosa and/or atrophy of the papillae of the tongue, with fissuring and ulcerations

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Diseases of Salivary glands

Xerostomia

Complications include increased rates of dental caries and candidiasis, as well as difficulty in swallowing and speaking.

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Diseases of Salivary glands

Sialadenitis (inflammation of the salivary glands)

May be induced by trauma, viral or bacterial infection,

or autoimmune disease.

Viral sialadenitis: the most common form is mumps

Mumps predominantly involves the parotids, and

causes enlargement of salivary glands.

Mumps produces interstitial inflammation marked by a

mononuclear inflammatory infiltrate.

Mumps in children is most often a self-limited benign

condition, in adults it can cause pancreatitis or orchitis.

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Diseases of Salivary glands

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Diseases of Salivary glands

Bacterial sialadenitis

The most frequent pathogens are Staphylococcus aureus

and Streptococcus viridans

Bacterial sialadenitis most often involves the

submandibular glands.

Dehydration and decreased secretory function can

predispose to bacterial invasion.

Autoimmune sialadenitis (Sjögren syndrome).

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Diseases of Salivary glands

Mucocele

Most common inflammatory lesion of the salivary glands

Results from blockage/rupture of a salivary gland duct, with consequent leakage of saliva into the surrounding connective tissue stroma.

Presents with fluctuant swelling of the lower lip that may change in size, particularly in association with meals

Rx: complete excision.

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Diseases of Salivary glands

Mucocele

Cyst-like space lined by granulation tissue or fibrous connective tissue that is filled with mucin and inflammatory cells, particularly macrophages

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Diseases of Salivary glands

Salivary gland neoplasms

2% of all human tumors

65% to 80% arise within the parotid gland, 10% in the submandibular gland, and the remainder in the minor salivary glands, including the sublingual glands

Clinically, parotid gland neoplasms produce swelling in front of and below the ear.

Benign tumors are slow growing (months to years)

Malignant more often come to attention promptly, probably because of their more rapid growth.

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Diseases of Salivary glands

The likelihood that a salivary gland tumor is

malignant is inversely proportional, roughly, to the

size of the gland:

15% to 30% of tumors in the parotid glands are

malignant

In contrast, approximately 40% of submandibular,

50% of minor salivary gland,

70% to 90% of sublingual tumors are malignant.

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Diseases of Salivary glands

➢Most common benignsalivary gland tumor is pleomorphic adenoma

➢Most common malignant salivary gland tumor is Mucoepidermoid carcinoma

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Diseases of Salivary glands

Pleomorphic Adenoma (mixed tumor)

Benign tumors

Consist of a mixture of ductal (epithelial) and

myoepithelial cells (mesenchymal)

PA represent 60% of tumors in the parotid, are less

common in the submandibular glands and others

Slow-growing, painless, mobile discrete masses

They recur if incompletely excised

Page 73: Introduction to the GIT system

Diseases of Salivary glands

(Pleomorphic Adenoma)

Pleomorphic adenomas typically manifest as rounded, well-demarcated masses rarely exceeding 6 cm in the greatest dimension

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Diseases of Salivary glands

They are encapsulated,

The cut surface is gray-white and typically contains myxoid and blue translucent chondroid (cartilage-like) areas.

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Diseases of Salivary glands

(Pleomorphic Adenoma)

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Diseases of Salivary glands

(Pleomorphic Adenoma)

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Diseases of Salivary glands

Pleomorphic Adenoma (mixed tumor)

Carcinoma arising in a pleomorphic adenoma is referred

to variously as a “carcinoma ex pleomorphic adenoma”

or “malignant mixed tumor”.

The incidence of malignant transformation increases with

time (2% if less than 5 years) and (10% if present more

than 15 years).

The cancer usually takes the form of an adenocarcinoma.

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Diseases of Salivary glands

Mucoepidermoid Carcinoma (MEC)

Mucoepidermoid Carcinoma (MEC)

Malignant neoplasm of variable biologic aggressiveness

MEC are composed of variable mixtures of squamous cells, mucus-

secreting cells, and intermediate cells.

MEC is the most common form of primary malignant tumor of the

salivary glands (15% of all salivary gland tumors)

They occur mainly (60%–70%) in the parotids

Clinical course and prognosis depend on histologic grade

Recur in 25% to 30% of cases, and about 30% metastasize to distant

sites.

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Diseases of Salivary glands

Mucoepidermoid Carcinoma (MEC)

Gross pathology:

Well-circumscribed to partially encapsulated to unencapsulated

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Mucoepidermoid Carcinoma (MEC)

Solid areas of the tumor are formed by different proportions of epidermoid (squamous) cells (red arrow), mucus cells (green arrow) and intermediate cells (yellow arrow)

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Diseases of Salivary glands

Mucoepidermoid Carcinoma (MEC)

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Diseases of Salivary glands

Mucoepidermoid Carcinoma (MEC)