Pathology of the Gastro Intestinal Tract part I
ObjectivesUpon successful completion of this lectures, students should be able to: Identify and describe the major disease processes including, inflammation, neoplasm and malabsorption conditions affecting different organs of GIT (oral cavity, esophagus, stomach, small and large intestine) in terms of, etiology pathogenesis, gross and microscopic changes, manifestations, and complications. Identify various bacterial, viral, fungal, and parasitic infections affecting GIT, and describe the principle manifestations, diagnosis, treatment, and prevention of each individual microorganism and parasitic agent affecting GIT.
PROLIFERATIVE LESIONS OF THE ORAL CAVITY The most common proliferative lesions of the oral cavity are 1. Irritation Fibroma 2. Ossifying fibroma 3. Pyogenic granuloma 4. Peripheral giant cell granuloma
Irritation” fibroma A nodular mass of fibrous tissue that occurs mainly in the buccal mucosa along the bite line & gingivo-dental margin.
A highly vascular lesion that is usually seen in the gingiva of children, young adults, and pregnant women (pregnancy tumor). It is typically ulcerated & bright red in color (due to rich vascularity)
Pyogenic granuloma
PYOGENIC GRANULOMAThere’s vascular proliferation (granulation tissue- like) covered by stratified squamous epithelium (oral mucosa). The lesion either regresses (esp. after pregnancy), or undergoes fibrous maturation and may develop into ossifying fibroma.
A relatively common lesion that Protrudes from the gingiva as a reddish mass at sites of chronic inflammation.
Peripheral giant cell granuloma (giant cell epulis)
Peripheral Giant Cell Granuloma
Aggregates of multinucleated giant cells separated by a fibro-vascular stroma
INFLAMMATORY CONDITIONS OF THE ORAL CAVITY Inflammatory ulcerations The most common inflammatory ulcerations of the oral cavity are 1. Traumatic 2. Aphthous 3. Herpetic Traumatic ulcers: usually the result of trauma (e.g. fist fighting) or licking a jagged tooth.
Aphthous ulcers Very common, single or multiple, painful, recurrent, superficial ulcerations of the oral mucosa covered by a thin yellow exudate rimmed by a narrow zone of erythema
Glossitis (with ulcerations) may be seen with Nutritional deficiency states Jagged carious teeth Ill-fitting dentures Exposure to hot fluids or corrosive chemicals Inhalation of burn fumes including excessive smoking Syphilis Plummer-Vinson syndrome is a combination of Iron-deficiency anemia Glossitis Esophageal dysphagia (due to esophageal webs)
Herpes simplex infectionsMost of these are caused by (HSV) type 1 >>> 2Primary HSV infection typically occurs in children aged 2 to 4 years; is often asymptomatic, but sometime it presents as acute herpetic gingivostomatitis, characterized by vesicles and ulcerations throughout the oral cavity. The great majority of affected adults harbor latent HSV-1 (the virus migrates along the regional nerves and eventually becomes dormant in the local ganglia e.g., the trigeminal. In some individuals, usually young adults, the virus becomes reactivated to produce the common but usually mild cold soreلطمة حمى .
Gingivostomatitis Herpetica
characterized by vesicles & ulcerations throughout the oral cavity and lips.Vesicle in epidermis due to Intracellular & intercellular edema squamous cell ncrosis & acantholysis
Characteristic nuclear changes multinucleation, molding, Chromatin margination
Herpes simplex infection of the lip
The viral infection is associated with intracellular and intercellular edema, yielding clefts that may become transformed into vesicles. The vesicles range from a few millimeters to large ones that eventually rupture to yield extremely painful, red-rimmed, shallow ulcerations. 2. Other Viral Infections - Herpes zoster - EBV (infectious mononucleosis) - CMV - Enterovirus - Measles
3. Oral Candidiasis (thrush) This is the most common fungal infection of the oral cavity. The thrush is a grayish white, superficial, inflammatory psudomembrane composed of the fungus enmeshed in a fibrino-suppurative exudates. This can be readily scraped off to reveal an underlying red inflammatory base. The fungus is a normal oral flora but causes troubles only 1. In the setting of immunosuppression (e.g. diabetes mellitus, organ or bone marrow transplant recipients, neutropenia, cancer chemotherapy, or AIDS) or 2. When broad-spectrum antibiotics are taken; these eliminate or alter the normal bacterial flora of the mouth. 3. In infants, where the condition is relatively common, presumably due to immaturity of the immune system in them.
Oral candidiasis
thrush in a child Oral thrush in an adultTHRUSH is formed of dense clumps of hyphae (approx. 1 mm thick), present on the surface of the stratified squamous epithelium that are stained purplish-red, are invading the epithelium almost to the basal layer (right). Desquamating cells (left) mingle with the hyphae. The epithelium is tending to separate from the basal layers (right). Inflammatory cells are present throughout the epithelium and in the submucosa (right).
ORAL CANDIDIASIS PAS STAIN
4. Deep Fungal Infections Some fungal infections may extends deeply to involve the muscles & bones in relation to oral cavity. These include, among others, histoplasmosis, blastomycosis, and aspergillosis. The incidence of such infections has been increasing due to increasing number of patients with AIDS, therapies for cancer, & organ transplantation 5. Diphtheria: characterized grossly by dirty white, fibrino-suppurative, tough, inflammatory pseudomembrane over tonsils & posterior pharynx.
DIPHTHERIA
Dirty white, fibrinosuppurative, tough, inflammatory pseudomembrane over tonsils & posterior pharynxORAL MANIFESTATIONS OF SYSTEMIC DISEASE Many systemic diseases are associated with oral lesions & it is not uncommon for oral lesions to be the first manifestation of some underlying systemic condition. 1. Scarlet fever: strawberry tongue: white coated tongue with hyperemic papillae projecting 2. Measles: Koplik spots: small whitish ulcerations (spots) on a reddened base, about Stensen duct 3. Diphtheria: dirty white, fibrinosuppurative, tough pseudomembrane over the tonsils and retropharynx 4. AIDS a. opportunistic oral infections: herpesvirus, Candida, other fungi b. Kaposi sarcoma c. hairy leukoplakia 5. AML (especially monocytic leukemia): enlargement of the gingivae + periodontitis 6. Melanotic pigmentation Addison disease hemochromatosis fibrous dysplasia of bone Peutz-Jegher syndrome 7. Pregnancy: pyogenic granuloma ("pregnancy tumor")
Strawberry tongue of scarlet fever
White coated tongue with hyperemic papillae projectingSmall, white ulcers (spots) on a reddened background that occur on the inside of the cheeks early in the course of measles.
Koplik spots of measles
This HIV-positive patient presented with an intraoral Kaposi’s sarcoma lesion with an overlying candidiasis infection. Initially, the KS lesions are flattened and red, but as they age they become raised, and darker, tending to a purple coloration. Kaposi sarcoma of AIDS
Gum in AML
Acute myeloid leukemia may present as gum infiltrates, especially in cases of acute myelomonocytic leukemia (FAB M4) and monoblastic leukemia (FAB M5).Mouth pigmentation in various diseases
Addison diseasePeutz Jegher syndrome
PRECANCEROUS LESIONS OF THE ORAL CAVITY Leukoplakia and Erythroplakia are considered premalignant lesions of squamous cell carcinoma. Leukoplakia is a white patch that cannot be scraped off and cannot be attributed clinically or microscopically to any other disease i.e. if a white lesion in the oral cavity can be given a specific diagnosis it is not a leukoplakia. As such, white patches caused by entities such as candidiasis are not leukoplakias. All leukoplakias must be considered precancerous (have the potential to progress to squamous cell carcinoma) until proved otherwise through histologic evaluation.
Leukoplakia is highly variable and can range from A, smooth and thin with well-demarcated borders. B, diffuse and thick. C, irregular with a granular surface. D, diffuse & corrugated.
Erythroplakias Are red velvety patches Much less common, yet much more serious than leukoplakias. The incidence of dysplasia and thus the risk of complicating squamous cell carcinoma is much more frequent in erythroplakia compared to leukoplakias. Both leukoplakia and erythroplakia are usually found between ages of 40 and 70 years Much commoner in males than females. The use of tobacco (cigarettes, pipes, cigars, and chewing tobacco) is the most common incriminated factor.
Erythroplakia A, Lesion on maxillary gingiva. B, Red lesion on mandibular alveolar ridge.
Severe dysplasia amounting to CIS
80% of patients have HIV; 20% associate other immunodeficiency states. Caused by EBV When hairy leukoplakia precedes HIV infection, manifestations of AIDS generally appear within 2 - 3 years.
HAIRY LEUKOPLAKIA White, confluent patches of fluffy ("hairy"), hyperkeratotic thickenings, almost always situated on the lateral border of the tongue
Squamous cell carcinoma 95% of cancers of the head and neck are squamous cell carcinomas; these arise most commonly in the oral cavity. The 5-year survival rate of: Early-stage oral cancer is approximately 80%, Late-stage disease is about 20%. This highlight the importance of early diagnosis & treatment, optimally of the precancerous lesions. SCC may arise anywhere in the oral cavity, but the favored locations are The tongue 2. Floor of mouth 3. Lower lip 4. Soft palate 5. Gingiva As a group, these tumors tend to infiltrate and extend locally before they eventually metastasize to cervical lymph nodes and more remotely. The most common sites of distant metastasis are mediastinal lymph nodes, lung, liver and bones
The pathogenesis of squamous cell carcinoma is multifactorial: 1. Chronic smoking & alcohol consumption 2. Oncogenic variants of (HPV). 50% of oropharyngeal cancers, particularly those of the tonsils & the base of tongue, harbor oncogenic variants of HPV. 3. Inheritance of genomic instability; a family history of head and neck cancer is a risk factor. 4. Exposure to actinic radiation (sunlight) & pipe smoking are known predisposing factors for cancer of the lower lip.
SQUAMOUS CELL CARCINOMA LATERAL BORDER OF TONGUE
Leukoplakia-likeulcerative
Fungating
Erythroplakia-like
A squamous cell carcinoma presenting as a verroucous keratotic lesion of the marginal gingiva, in a 54 year old male patient.
Squamous cell carcinoma of the lower gingiva. Presenting as a deeply ulcerative lesion, in a 65 year old female patient.
Floor of Mouth Squamous Cell Carcinoma
Indurated, slowly growing lesion of the lower lip.Squamous cell carcinoma of lower lip
Well differentiated SCC
Sheets of well-differentiated SCC showing keratin nestsRound cells without obvious squamous differentiation
Poorly-differentiated SCCSALIVARY GLANDS There are three major salivary glands—parotid, submandibular, and sublingual. Additionally, there are numerous minor salivary glands distributed throughout the mucosa of the oral cavity. Xerostomia refers to dry mouth due to a lack of salivary secretion; the causes include1. Sjцgren syndrome: an autoimmune disorder, that is usually also accompanied by involvement of the lacrimal glands that produces dry eyes (keratoconjunctivitis sicca).2. Radiation therapyInflammation (Sialadenitis) Sialadenitis refers to inflammation of a salivary gland; it may beTraumatic 2. Infectious: viral, bacterial3. AutoimmuneThe most common form of viral sialadenitis is mumps, which usually affects the parotids. The pancreas and testes may also be involved.
Bacterial sialadenitis is seen as a complication of Stones obstructing ducts of a major salivary gland (Sialolithiasis), particularly the submandibular. 2. Dehydration with decreased secretory function as is sometimes occurs in a. patients on long-term phenothiazines that suppress salivary secretion. b. elderly patients with a recent major surgery. Unilateral involvement of a single gland is the rule and the inflammation may be suppurative. The inflammatory involvement causes painful enlargement and sometimes a purulent ductal discharge.
Mucocele This is common salivary lesion results from interruption of salivary outflow due to blockage or rupture of a salivary gland duct. This leads to seepage of saliva into the surrounding tissues. The lower lip is the most common location due to exposure of this site to trauma (fist fighting, falling etc.). It presents as fluctuant swelling. Microscopically, there is accumulation of mucin with inflammatory cells. Ranula is a mucocele of the sublingual gland; it may become extremely large.
chronic inflammatory cell infiltrates along with fibrosis and acinar atrophy
Chronic sialadenitisSalivary gland neoplasms
Benign and malignant salivary tumors Uncommon, < 2% of all tumors Salivary gland tumors Relative frequency (%)Parotid gland up to 80%Submandibular gland about 10%, Minor salivary & sublingual glands about 10% Usually occur in adults- Benign tumors occur around age of 50- 60 yr- malignant tend to appear in older age groups Slight female predominance (EXCEPT Warthin’s T.)The incidence of malignant tumors within salivary glands: Salivary gland affected Relative frequency of malignant tumors Sublingual tumors 80% Minor salivary glands 50% Submandibular glands 40% Parotid glands 25% Parotid tumors produce swellings in front/below the ear Clinically, no reliable criteria to differentiate benign from malignant; pathological evaluation is necessary
CLINICAL APPEARANCE OF PAROTID TUMORS
PLEOMORPHIC ADENOMAS (MIXED SALIVARY GLAND TUMOR)constitute about 60% of tumors in the parotid less common in submandibular/rare in minor salivary Derived from ductal epithelial/myoepithelial reserve cells Exposure to radiation is a predisposing factor
Pleomorphic Adenomas (Mixed Salivary Gland Tumors) These benign tumors commonly occur within the parotid gland (constitute 60% of all parotid tumors). Gross features Most tumors are rounded, encapsulated masses. The cut surface is gray-white with myxoid and light blue translucent areas of chondroid. Microscopic features The main constituents are a mixture of ductal epithelial and myoepithelial cells, and it is believed that all the other elements, including mesenchymal, are derived from the above cells (hence the name adenoma). The epithelial/myoepithelial components of the neoplasm are arranged as glands, strands, or sheets. These various epithelial/myoepithelial elements are dispersed within a background of loose myxoid tissue that may contain islands of cartilage-like islands and, rarely bone. Sometimes, squamous differentiation is present. In some instances, the tumor capsule is focally deficient allowing the tumor to extend as tongue-like protrusions into the surrounding normal tissue. Enucleation of the tumor is, therefore, not advisable because residual foci (the protrusions) may be left behind and act as a potential source of multifocal recurrences. The incidence of malignant transformation increases with the duration of the tumor.
PLEOMORPHIC ADENOMA Present as rounded encapsulated mass, rarely exceed 6 cm in diameter.
Cut surface gray-white with myxoid and blue translucent areas of Chondroid differentiation.Tumor capsule may be focally deficient extension as tongue-like protrusions into the surrounding normal tissue
Pleomorphic adenoma (mixed tumor) of salivary gland is shown extending into surrounding normal parotid gland
Epithelial duct-like structures are seen in loose and dense connective tissue stroma
The neoplastic ducts are surrounded by a myxomatoid stroma. Also note the eosinophilic secretory product in the epithelial duct.The glandular epithelium dominates this section.
Sheets of epithelial cells with some keratin "pearls" are evident in this section.The stroma has a "cartilagenous" appearance; blood vessels are also prominent in this section.
Epithelial ducts in a dense c.t. stroma that resemble ostoid material, an observation supported by the nearby calcified bone.
Recurrence of mixed tumor Although this is a bizarre example, it demonstrates well the multinodularity so typical of recurrent tumor. The reason for this is that during the first surgical procedure many small pieces of tumor were distributed throughout the operative site and each formed the nidus for a recurrent mass.
Recurrent mixed salivary gland tumor
Enucleation of tumor is not advisable residual foci & multifocal recurrences Surgical technique Recurrence rate Adequate parotidectomy 4% Enucleation 25%Malignant transformation occur in 5-10% of patients Adenocarcinoma/undifferentiated carcinoma Incidence of malignant transformation is proportional to duration- 2% for tumors < 5 yr- 10% for tumors > 15 yr
Warthin Tumor Is the second most common salivary gland neoplasm. It is benign, arises usually in the parotid gland and occurs more commonly in males than in females. About 10% are multifocal and 10% bilateral. Smokers have a higher risk than nonsmokers for developing these tumors. Grossly, it is round to oval, encapsulated mass & on section display gray tissue with narrow cystic or cleft-like spaces filled with secretion. Microscopically, these spaces are lined by a double layer of neoplastic epithelial cells resting on a dense lymphoid stroma, sometimes with germinal centers. This lympho-epithelial lining frequently project into the spaces. The epithelial cells are oncoytes as evidenced by their eosinophilic granular cytoplasm (stuffed with mitochondria).
WARTHIN’S TUMOR Second most common neoplasm. Almost always in parotid/superficial lobe > males . 10% multifocal , 10% bilateralSmoking ↑ risk (X8) Round to oval, encapsulated masses, up to 5 cm in diameter; pale gray surface punctuated by cleft-like spaces; filled with mucoid secretions.
Warthin tumor
These tumours are multicystic. The cysts are filled with mucus, as indicated. They are benign tumours and are the second most frequent tumour of the parotid gland, following pleomorphic adenoma.lymphoid stroma with a covering of large double-layered oncocytic epithelial cells.
WARTHIN’S TUMOROvoid tumor with a smooth surface, multicystic lesion.Covering the surface of this lymphoid tissue are large double-layered oncocytic epithelial cells (have eosinophilic cytoplasm stuffed with mitochondria).
Mucoepidermoid Carcinoma As the name indicates, these neoplasms are composed of variable mixtures of mucus-secreting cells (muco), and squamous cells (epidermoid). They are the most common form of primary malignant tumor of the salivary glands. They occur mainly in the parotids. Low-grade tumors may invade locally but do not metastasize. By contrast, high-grade neoplasms metastasize to distant sites in 30% of cases. Grossly, mucoepidermoid carcinomas are gray-white, infiltrative tumors that frequently show small, mucin-containing cysts. Microscopically, there are cords, sheets, and cysts of squamous and mucous-secreting cells.
MUCOEPIDERMOID CARCINOMA
Saheets of squamous and mucus-secreting cellsOther Salivary Gland Tumors Two less common neoplasms worth brief description: Adenoid cystic carcinoma: half of the cases are found in the minor salivary glands (in particular the palate). Although slow growing, they have a tendency to invade perineural spaces and to recur. Eventually, 50% or more disseminate widely to distant sites such as bone, liver, and brain. Microscopically, they are composed of small cells having dark, compact nuclei and scant cytoplasm. These cells tend to be disposed in sieve-like (cribriform) patterns. The spaces between the tumor cells are often filled with a hyaline material thought to represent excess basement membrane. Acinic cell tumor is composed of cells resembling the normal acinar cells (hence the name). Most arise in the parotids; the small remainder arises in the submandibular glands. On histologic examination, they reveal a variable architecture and cell morphology. Most characteristically, the cells have clear cytoplasm & are disposed in sheets, microcysts, glands, or papillae. About 10% to 15% of these neoplasms metastasize to lymph nodes.
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Adenoid cystic carcinoma palate
Adenoid cystic carcinoma
Small cells with dark nuclei & scant cytoplasm Disposed in cribriform pattern Spaces filled with mucin & excess BM materialAdenoid cystic carcinoma with prominent perineurial invasion.
Adenoid cystic carcinomaNerve
ESOPHAGUS The main functions of the esophagus are to: 1. Conduct food and fluids from the pharynx to the stomach 2. Prevent reflux of gastric contents into the esophagus. These functions require motor activity coordinated with swallowing, i.e. wave of peristalsis, associated with relaxation of the LES in anticipation of the peristaltic wave. This is followed by closure of the LES after the swallowing reflex. Maintenance of sphincter tone (positive pressure relative to the rest of esophagus) is necessary to prevent reflux of gastric contents.
CONGENITAL ANOMALIES OF THE ESOPHAGUS Several congenital anomalies affect the esophagus including Ectopic gastric mucosa & Ectopic pancreatic tissues within the esophageal wall, congenital cysts & congenital herniation of the esophageal wall into the thorax. The latter is due to impaired formation of the diaphragm. Esophageal atresia & fistulas
LESIONS ASSOCIATED WITH MOTOR DYSFUNCTION Coordinated motor activity is important for proper function of the esophagus. The major entities that are caused by motor dysfunction of the esophagus are 1. Achalasia 2. Hiatal hernia 3. Diverticula 4. Mallory-Weiss tear Achalasia Achalasia means "failure to relax." It is characterized by three major abnormalities: 1. Aperistalsis (failure of peristalsis) 2. Increased resting tone of the LES 3. Incomplete relaxation of the LES in response to swallowing In most instances, achalasia is an idiopathic disorder. In this condition there is progressive dilation of the esophagus above the persistently contracted LES. The wall of the esophagus may be of normal thickness, thicker than normal owing to hypertrophy of the muscular wall, or markedly thinned by dilation (when dilatation overruns hypertrophy). The mucosa just above the LES may show inflammation and ulceration. Young adults are usually affected and present with progressive dysphagia.
Achalasia means "failure to relax." It is characterized by: 1. Aperistalsis (failure of peristalsis) 2. Increased resting tone of the LES 3. Icomplete relaxation of the LES in response to swallowing
Achalasia: Inability to relax lower esophageal sphincter leads to massive esophageal dilation above level of persistently contracted LES.
Complications of achalasia are 1. Aspiration pneumonitis of undigested food 2. Monilial esophagitis 3. Esophageal squamous cell carcinoma ( about 5% of patients) 4. Lower esophageal diverticula
Achalasia Dorsal view with the massively dilated esophagus opened longitudinally.
Achalasia esophagus
Hiatal Hernia Hiatal hernia is characterized by separation of the diaphragmatic crura leading to widening of the space around the esophageal wall. Two types of hiatal hernia are recognized: 1. The sliding type (95%) 2. The paraesophageal type In the sliding hernia the stomach skates up through the patent hiatus above the diaphragm creating a bell-shaped dilation. In paraesophageal hernias, a separate portion of the stomach, usually along the greater curvature, enters the thorax through the widened foramen. The cause of hiatal hernia is unknown. It is not clear whether it is a congenital malformation or is acquired during life. Only about 10% of adults with a sliding hernia suffer from heartburn or regurgitation of gastric juices into the mouth. These are due to incompetence of the LES and are accentuated by positions favoring reflux (bending forward, lying supine) and obesity. Complications of hiatal hernias include 1. Ulceration, bleeding and perforation (both types) 2. Reflux esophagitis (frequent with sliding hernias) 3. Strangulation of paraesophageal hernias
Sliding hiatal hernia
In a sliding hiatal hernia, part of the stomach moves through the diaphragm so that it is positioned outside of the abdomen and in the chest. The lower esophageal sphincter (LES) often moves up above its normal location in the opening of the diaphragm.Hiatal hernia paraeosphgeal & mixed
In a paraesophageal hernia, the stomach bulges up through the opening in the diaphragm (hiatus) alongside the esophagus (upside-down stomach). The LES remains in its normal location inside the opening of the diaphragm. This type of hernia most commonly occurs when there is a large opening in the diaphragm next to the esophagus. The stomach and, rarely, other abdominal organs (such as the intestine, spleen, and colon) may also bulge into the chest in a paraesophageal hernia. MIXED HERNIA in a mixed hiatal hernia, the LES is above the diaphragm as in a sliding hiatal hernia, and the stomach is alongside the esophagus as in a paraesophageal hiatal hernia.Diverticula By definition a diverticulum is a "focal out pouching of the alimentary tract wall that contains all or some of its constituents"; they are divided into 1. False diverticulum is an out pouching of the mucosa and submucosa through weak points in the muscular wall. 2. True diverticulum consists of all the layers of the wall and is thought to be due to motor dysfunction of the esophagus. They may develop in three regions of the esophagus a. Zenker diverticulum, located immediately above the UES b. Traction diverticulum near the midpoint of the esophagus c. Epiphrenic diverticulum immediately above the LES
Lacerations (Mallory-Weiss Syndrome)These are longitudinal tears at the GEJ or gastric cardia as a consequence of severe retching or vomiting. They are encountered most commonly in alcoholics, (susceptible to episodes of excessive vomiting). Prolonged vomiting Failure of reflex relaxation of LES The refluxing gastric contents suddenly overcome the contracted musculature leading to forced, massive dilation of the lower esophagus with tearing of the stretched wall. The tears may involve only the mucosa or may penetrate deeply. Esophageal rupture is rare. Infection of the mucosal defect may lead to inflammatory ulcer or to mediastinitis. Usually the bleeding is not profuse and stops without surgical intervention. Healing is the usual outcome.
Mallory-Weiss tear
This is a tear in the mucosal layer at the junction of the esophagus and stomachImage demonstrates a thin, linear tear (arrow) beginning just above the squamocolumnar junction and extending proximally.
Esophageal lacerations (Mallory-Weiss syndrome)
Photograph demonstrating longitudinal lacerations oriented in the axis of the esophageal lumen (arrow), extending from the esophageal mucosa to the stomach mucosa.Esophageal mucosa
Gastric mucosa
Longitudinal tear
Esophageal Varices Portal hypertension when sufficiently prolonged or severe induces the formation of collateral bypass veins wherever the portal and caval venous systems communicate. Esophageal varices refer to the dilatation of deep mucosal and submucosal venous collaterals of the lower esophagus subsequent to the diversion of portal blood through them through the coronary veins of the stomach. From the varices the blood is diverted into the azygos veins, and eventually into the systemic veins. Varices develop in 90% of cirrhotic patients. Worldwide, after alcoholic cirrhosis, hepatic schistosomiasis is the second most common cause of variceal bleeding.
Tortuous dilated veins of the distal esophagus pushing the mucosa causing irregular protrusions into the lumen. Variceal rupture produces massive hemorrhage into the lumen.
ESOPHAGEAL VARICES
Esophagitis may be caused by a variety of physical, chemical, or biologic agents. 1- GERD (which is, in fact, a chemical injury), 2- Ingestion of mucosal irritants (such as alcohol, corrosive acids or alkalis as in suicide attempts), 3- Cytotoxic anticancer therapy, 4- Bacteremia or Viremia (in immunosuppressed patients). 5- Fungal infection (in immunosuppressed or debilitated patients or during broad-spectrum antimicrobial therapy; candidiasis by far the most common), 6- Uremia.
Reflux Esophagitis (Gastroesophageal Reflux Disease or GERD) is the most important cause of esophagitis. Characterized by reflux of gastric contents into the lower esophagus Caused by decreased efficacy of esophageal antireflux mechanisms, particularly LES tone. Contributing factors include: 1- CNS depressants including alcohol 2- Smoking 5- Sliding hiatal hernia 3- Pregnancy 6- hypothyroidism 4- Nasogastric tube 7- Systemic sclerosis Often more than one factor contributes in individual cases.
Reflux esophagitis- endoscopy
There is marked hyperemia (focal or diffuse) affecting the lower esophagus. Arrows point to erosions.Reflux esophagitis
Gross appearance of a severe case of reflux esophagitis. Marked hyperemia with focal hemorrhage is present in the area of reflux.Three histologic features are characteristic: Inflammatory cells esp. eosinophils within the squamous mucosa. Basal cells hyperplasia Extension of lamina propria papillae into the upper third of the mucosa.
GERD
The disease mostly affects those over the age of 40 years. The clinical manifestations consist of dysphagia, heartburn, regurgitation of a sour fluid into the mouth, hematemesis, or melena. Rarely, there are episodes of severe chest pain that may be mistaken for a "heart attack." The potential consequences of severe reflux esophagitis are 1. Bleeding 2. Ulceration 3. Stricture formation 4. Tendency to develop Barrett esophagus
Barrett esophagus is recognized as a red, velvety mucosa located in the middle and distal esophagus contrasting with the smooth, pale pink esophageal squamous mucosa and the light brown gastric mucosa. It is displayed as tongues, patches or broad circumferential bands replacing the squamo- columnar junction for several centimeters.
In Barett’s Esophagus the esophageal squamous epithelium is replaced by metaplastic columnar epithelium, including interspersed goblet cells, & may show a villous pattern (as that of the small intestine ( intestinal metaplasia).
Barrett's esophagus with complete intestinal metaplasia
Barret Esophagus : The most frequent metaplastic change is the presence of columnar cells admixed with goblet cells, thus the term "intestinal metaplasia" is used to describe the histological alteration.Barrett Esophagus (BE) 10% of patients with long-standing GERD develop this complication. Most patients with the first diagnosis of Barrett esophagus are between 40 and 60 years Barrett esophagus is clinically significant due to: 1. The secondary complications of local peptic ulceration with bleeding and stricture. 2. The development of adenocarcinoma, which in patients with long segment disease (over 3 cm of Barrett mucosa), occurs at a frequency that is 30-40 times >>> the general population. The pathogenesis of Barrett esophagus appears to be due to a change in the differentiation program of stem cells of the esophageal mucosa.
Criteria for the diagnosis of Barrett esophagus include: 1. Endoscopic evidence of columnar lining above the GEJ 2. Histologic confirmation of the above in biopsy specimens. Critical to the pathologic evaluation of patients with Barrett mucosa is the search for dysplasia within the metaplastic epithelium, which is the presumed precursor of malignancy. Dysplasia is recognized by the presence of cytologic and architectural abnormalities in the columnar epithelium, consisting of enlarged, crowded, and stratified hyperchromatic nuclei with loss of intervening stroma between adjacent glandular structures. Depending on the severity of the changes, dysplasia is classified as low-grade or high-grade. Approximately 50% of patients with high-grade dysplasia may already have adjacent adenocarcinoma. .
GERD BE
ComplicationsPeptic ulceration
bleeding strictureadenocarcinoma30 – 40 fold ↑rate over general population.
ESOPHAGEAL TUMORS Leiomyomas are the most common benign tumors of the esophagus. Carcinomas of the esophagus constitute (5% of all cancers of the GIT). They generally have a poor prognosis because they are often discovered too late. Worldwide, squamous cell carcinomas constitute 90% of esophageal cancers, followed by adenocarcinoma. Other tumors are rare. Squamous Cell Carcinoma (SCC) Usually affect adults over the age of 50. Commoner in males than females. The regions with high incidence include Iran & China. Commoner in Kurds of North Iraq. Blacks throughout the world are at higher risk than are whites.Etiology and Pathogenesis 1. Dietary Deficiency of vitamins (A, C, riboflavin, thiamine, and pyridoxine) & trace elements (zinc) Fungal contamination of foodstuffs High content of nitrites/nitrosamines Betel chewing (betel: leaf of a climbing evergreen shrub, of the pepper family, which is chewed in the East with a little ime.) 2. Lifestyle Burning-hot food Alcohol consumption Tobacco abuse 3. Genetic Predisposition Long-standing celiac disease Racial disposition
4. Esophageal Disorders Long-standing esophagitis Achalasia Plummer-Vinson syndrome
The marked geographical variations in the incidence of the disease strongly implicate dietary and environmental factors, with a contribution from genetic predisposition. The majority of cancers in Europe and the United States are attributable to alcohol and tobacco. Some alcoholic drinks contain significant amounts of such carcinogens as polycyclic hydrocarbons, nitrosamines, and other mutagenic compounds. Nutritional deficiencies associated with alcoholism may contribute to the process of carcinogenesis. Human papillomavirus DNA is found frequently in esophageal squamous cell carcinomas from high-incidence regions.
Squamous cell ca esophagus Exophytic (60%)
Cake-like exophytic mass.Elevated round nodule with central ulceration.
20% in the upper third, 50% in the middle third 30% in the lower third
Circumferential infiltrative constricting lesion (15%)
Ulcerative (25%).The majority of esophageal squamous cell carcinomas are well to moderately differentiated
squamous cell carcinoma esophagusLocal extension into adjacent mediastinal structures occurs early, possibly due to the absence of serosa for most of the esophagus.Lymphatic spread: The rich lymphatic network in the submucosa promotes extensive circumferential and longitudinal spread. upper third tumors cervical lymph nodes; middle third tumors mediastinal, paratracheal & tracheo-bronchial lymph nodes; Lower third most gastric & celiac groups of LNThe presence of lymph node metastases at the time of resection significantly reduces survivalCommonest clinical presentation is “progressive dysphagia”The five-year survival rate in patients in patients who undergo "curative" surgery is about 75% in superficial esophageal carcinoma 25% for more advanced disease.
Adenocarcinoma of Esophagus Etiology and Pathogenesis Most adenocarcinomas arise in the lower third of esophagus from the Barrett mucosa. The lifetime risk for cancer development from Barrett esophagus is approximately 10%. Tobacco exposure and obesity are risk factors. Helicobacter pylori infection may be a contributing factor.
Ulcerated, exophytic mass at GE junction, arising from the grnular mucosa of BE. The gray-white esophageal mucosa is on the top, and the folds of gastric mucosa are below.
Adenocarcinoma of esophagus presenting as a polypoid growth.
Foci of dysplastic mucosa are frequently present adjacent to the tumor
Adenocarcinoma esophagus
Adenocarcinomas arising in Barrett esophagus - occur in patients over the age of 40 years - it is more common in men than in women, - Commoner in whites more than blacks (in contrast to squamous cell carcinomas). Patients usually present because of dysphagia, progressive weight loss, bleeding and chest pain. The prognosis is as poor as that for other forms of esophageal cancer, with under 20% overall five-year survival. Identification and resection of early cancers with invasion limited to the mucosa or submucosa improves five-year survival to over 80%. Regression or surgical removal of Barrett esophagus has not yet been shown to eliminate the risk for adenocarcinoma.