NEET MDS Lessons
General Pathology
LARGE INTESTINE (COLON)
Congenital anomalies
1. Hirschsprung's disease produces a markedly distended colon, usually proximal to the rectum. Caused by a section of aganglionic colon, which failed to develop normally due to the absence of ganglion cells).
This results in bowel obstruction and distention of the bowel proximal to the affected area.
2. Imperforate anus is due to a failure of perforation of the membrane that separates the endodermal hindgut from the ectodermal anal dimple.
Benign conditions
1. Diverticular disease refers to multiple outpouchings of the colon.
Incidence. Diverticular disease is present in 30%-50% adult autopsies in the United States. There is a higher dence with increasing age.
Pathogenesis. Herniation of mucosa and submucoq through weak areas of the gut wall where arterial vasa recta perforate the muscularis is a characteristic pathological finding of the disease.
Clinical features
- Diverticulosis is often asymptomatic, but may present with pain and/or rectal bleeding.
- In contrast, diverticulitis presents with pain and fever. It is distinguished from diverticulosis by the presence of inflammation, which may or may not cause symptom.
When symptomatic, the patlent experiences colicky left lower abdominal pain, change in bowel habits, and melena, so-called " left-sided appendicitis."
Pathology
Grossly, diverticula are seen most frequently in the sigmoid colon.
Inflammatory diseases
1. Crohn's disease, or regional enteritis, causes a segmental, recurrent, granulomatous inflammatory disease of the bowel. It most commonly involves the terminal ileum and colon but may involve any part of the gastrointestinal tract. There is a familial disposition.
Etiology.
There is probably a similar etiology for both Crohn's disease and ulcerative colitis, which together are called inflammatory bowel disease. The following possible etiologies have been considered: infectious; immunologic (both antibody-mediated and cell-mediated); deficiencies of suppressor cells; and nutritional, hormonal, vascular, and traumatic factors.
Clinical features.
Crohn's disease usually begins in early adulthood and is common in Ashkenazic Jews. Patients present with colicky pain, diarrhea, weight loss, malaise, malabsorption, low-grade fever, and melena. There is typically a remitting and relapsing course. If the involved bowel is resected, lesions frequently develop in previously uninvolved regions of the bowel.
Pathology. Crohn's disease has a very characteristic pathology.
Grossly, there are segmental areas (skip lesions) of involvement, most commonly in the terminal ileum.
3. Ulcerative colitis is a chronic relapsing disease characterized by ulcerations, predominantly of the rectum and left colon, but which may affect the entire colon and occasionally the terminal ileum.
Incidence is higher in Caucasians than in Blacks, and is also more frequent in women than in men. The typical age of onset ranges from 12-35 years of age. There is a definite familial predisposition.
Etiology. Etiologic theories are similar to those for Crohn's disease. Some inflammatory bowel disease has microscopic features of both ulcerative colitis and Crohn's disease.
Clinical course is characterized by relapsing bloody mucus diarrhea, which may lead to dehydration and electrolyte imbalances, lower abdominal pain, and cramps. There is an increased incidence of carcinoma of the colon, up to 50% after 25 years with the disease.
Pathology
Grossly, the disease almost always involves the rectum. It may extend proximally to involve part of the colon or its entirety. There are superficial mucosal ulcers, shortening of the bowel, narrowing of the lumen, pseudopolyps, and backwash ileitis.
In contrast to Crohn's disease, the inflammation is usually confined to the mucosa and submucosa.
Pseudomembranous colitis is an inflammatory process characterized by a pseudomembranous exudate coating the colonic mucosa
Pathogenesis. The syndrome is associated with antibiotic use (especially clindamycin), allowing proliferation of Clostridium difficile, which produces an exotoxin.
Clinical features include diarrhea that is often bloody, fever, and leukocytosis.
Diagnosis is made by identification of C. difficile and toxin in stool.
Treatment includes stopping the original antibiotic and starting oral vancomycin or metronidazole. This disease is often a terminal complication in immunosuppressed patients.
Vascular lesions
Hemorrhoids are variceal dilatations of the anal and perianal venous plexus. They are caused by elevated intra-abdominal venous pressure, often from constipation and pregnancy and are occasionally due to portal hypertension, where they are associated with esophageal varices. Hemorrhoids may under thrombosis, inflammation, and recanalization. External hemorrhoids are due to dilatation of the inferior hemorrhoidal
plexus, while internal hemorrhoids are due to dilatation of the superior hemorrhoidal plexus.
Polyps are mucosal protrusions.
1. Hyperplastic polyps comprise 90% of all polyps. They are no neoplastic and occur mostly in the rectosigmoid colon.
Grossly, they form smooth, discrete, round elevations.
2. Adenomatous polyps are true neoplasms. There is a higher incidence of cancer in larger polyps and in those containing a greater proportion of villous growth.
a. Tubular adenomas (pedunculated polyps) make up 75% of adenomatous polyps. They may be sporadic or familial
For sporadic polyps, the ratlo of men to women is 2:1. The average age of onset is 60.
Grossly, most occur in the left colon. Cancerous transformation (i.e., invasion of the lamina propria or the stalk) occurs in approximately 4% of patients.
b. Villous adenomas are the largest, least common polyps, and are usually sessile. About one-third are cancerous. Most are within view of the colonoscope.
(1) Grossly, they form "cauliflower-like" sessile growth 1-10 cm in diameter, which are broad-based and have no stalks.
3. Familial polyposis is due to deletion of a gene located on chromosome 5q.
Familial multiple polyposis (adenomatous polyposis coli) shows autosomal dominant inheritance and the appearance of polyps during adolescence; polyps start in the rectosigmoid area and spread to cover the entire colon. The polyps are indistinguishable from sporadic adenomatous polyps. Virtually all patients develop cancers. When diagnosed, total colectomy is recommended.
Gardner's syndrome refers to colonic polyps associated with other neoplasms (e.g., in skin, subcutaneous tissue, bone) and desmoid tumors. The risk of colon cancer is nearly 100%.
Peutz-Jeghers syndrome presents with polyps on the entire gastrointestinal tract (especially the small intestine) associ-
ated with melanin pigmentation of the buccal mucosa, lips, palms, and soles. The polyps are hamartomas and are not premalignant. Peutz-Jeghers syndrome shows autosomal dominant inheritance.
Turcot's syndrome is characterized by colonic polyps associated with brain tumors (i.e., gliomas, medulloblastomas).
Malignant tumors
Adenocarcinoma is the histologic type of 98% of all colonic cancers. Both environmental and genetic factors have been
identified.
Incidence is very high in urban, Western societies. It is the third most common tumor in both women and men. The peak incidence
is in the seventh decade of life.
Pathogenesis is associated with villous adenomas, ulcerative colitis, Crohn's disease, familial polyposis, and Gardner's syndrome. lncidence is possibly related to high meat intake, low-fiber diet, and deficient vitamin intake. A number of chromosomal abnormalities hme been associated with the development of colon cancer.
Clinical features include rectal bleeding, change in bow habits, weakness, malaise, and weight loss in high-stage disease. The tumor spread by direct metastasis to nodes, liver, lung, and bones. carcinoembryonic antigen (CEA) is a tumor marker that helps to monitor tumor recurrence after surgery or tumor progression in some patients.
Pathology
(1) Grossly, 75% of tumors occur in the rectum and sigmoid colon.
(2) Microscopically, these tumors are typical mucin-producing adenocarcinomas.
2. Squamous cell carcinoma forms in the anal region. It is often associated with papilloma viruses and its incidence is rising in homosexual males with AIDS.
N. meningiditis
Major cause of fulminant bacteremia and meningitis. Has a unique polysaccharide capsule. It is spread person to person by the respiratory route. Frequently carried in nasopharynx, and carriage rates increased by close quarters. Special risk in closed populations (college dorms) and in people lacking complement. Sub-saharan Africa has a “meningitis belt.”
Pathogenesis is caused by adherence factors that attach to non-ciliated nasopharyngeal epithelium. These factors include pili which promote the intial epithelial (and erythrocyte) attachment, and Opa/Opc surface binding proteins.
Adherence stimulates engulfment of bacteria by epithelial cells. Transported to basolateral surface.
The polysaccharide capsule is a major virulence factor that prevents phagocytosis and lysis.
A lipo-oligosaccharide endotoxin also contributes to sepsis.
Bacillus anthrax
- large Gram (+) rods that produce heat resistant spores; Clostridia and Bacillus species are the two bacterial spore formers; they do not form spores in tissue; produces a powerful exotoxin.
- contracted by direct contact with animal skins or products
- four forms of anthrax are recognized → cutaneous (MC), pulmonary, oraloropharyngeal, and gastrointestinal.
- cutaneous anthrax (90 to 95% of cases) occurs through direct contact with infected or contaminated animal products.
- lesions resemble insect bites but eventually swell to form a black scab, or eschar, with a central area of necrosis ("malignant pustule").
Cytopathologic techniques
Cytopathology is the study of cells from various body sites to determine the cause or nature of disease.
Applications of cytopathology:
- Screening for the early detection of asymptomatic cancer
2. Diagnosis of symptomatic cancer
3. Surveillance of patients treated for cancer
Cytopathologic methods
There are different cytopathologic methods including:
1. Fine-needle aspiration cytology (FNAC) -In FNAC, cells are obtained by aspirating the diseased organ using a very thin needle under negative pressure.
Superficial organs (e.g. thyroid, breast, lymph nodes, skin and soft tissues) can be easily aspirated.
Deep organs, such as the lung, mediastinum, liver, pancreas, kidney, adrenal gland, and retroperitoneum are aspirated with guidance by fluoroscopy, ultrasound or CT scan.
- Exfoliative cytology
Refers to the examination of cells that are shed spontaneously into body fluids or secretions. Examples include sputum, cerebrospinal fluid, urine, effusions in body cavities (pleura, pericardium, peritoneum), nipple discharge and vaginal discharge.
- Abrasive cytology
Refers to methods by which cells are dislodged by various tools from body surfaces (skin, mucous membranes, and serous membranes). E.g. preparation of cervical smears with a spatula or a small brush to detect cancer of the uterine cervix at early stages.
Pemphigus
1. Ulcerative lesions on the skin and oral mucosa.
2. An autoimmune disease in which patients have autoantibodies against hemidemosomal attachment of epidermis cells.
3. Histologically characterized by acantholysis, in which epidermal cells appear to detach and separate from each other, as seen by Tzanck smears.
4. Can be life-threatening if untreated.
5. A positive Nikolsky sign is observed.
Because of sloughing of the epidermis, a red blister forms after pressure is applied to affected skin.
6. Treatment: corticosteroids.
Growth and spread of tumours
Growth in excess of normal is a feature of all tumours but extension to tissue away from the site of origin is a feature of malignant tumours.
Modes of spread of malignant tumours
- local, invasion. This is a feature of all malignant tumors and takes place along tissue spaces and facial planes
o Lymphatic spread. Most often seen in carcinomas. This can be in the form of
o Lymphatic permeation: Where the cells extend along the lymphatics as a solid core
o Lymphatic embolisation: Where a group of tumour cells break off and get carried to the draining mode
-Vascular spread : This is a common and early mode of spread for sarcomas but certain carcinomas like renal cell carcinoma and chorio carcinoma have a predilection to early vascular spread.
Vascular spread is most often due .to invasion of venous channels and can be by permeation or embolisation.
Lungs, liver, bones and brain are the common sites for vascular metastasis but
different tumours have different organ preference for metastasis, e.g. : Bronchogenic carcinoma often spreads to liver and adrenals.
-Body cavities and natural passages
o Gastrointestinal carcinomas spread to ovaries (Krukenberg’s tomour)
ADRENOCORTICAL TUMORS
Functional adenomas are commonly associated with hyperaldosteronism and with Cushing syndrome, whereas a virilizing neoplasm is more likely to be a carcinoma. Determination of of the functional status of a tumor is based on clinical evaluation and measurement of the hormone or its metabolites. In other words, functional and nonfunctional adrenocortical neoplasms cannot be distinguished on the basis of morphologic features.
Patholgical features
Adrenocortical adenomas
- They are generally small, 1 to 2 cm in diameter.
- On cut surface, adenomas are usually yellow to yellow-brown due to presence of lipid within the neoplastic cells
- Microscopically, adenomas are composed of cells similar to those populating the normal adrenal cortex. The nuclei tend to be small, although some degree of pleomorphism may be encountered even in benign lesions ("endocrine atypia"). The cytoplasm ranges from eosinophilic to vacuolated, depending on their lipid content.
Adrenocortical carcinomas
These are rare and may occur at any age, including in childhood.
- Carcinomas are generally large, invasive lesions.
- The cut surface is typically variegated and poorly demarcated with areas of necrosis, hemorrhage, and cystic change.
- Microscopically, they are composed of well-differentiated cells resembling those of cortical adenomas or bizarre, pleomorphic cells, which may be difficult to distinguish from those of an undifferentiated carcinoma metastatic to the adrenal.