NEET MDS Lessons
General Pathology
Bone-Forming Tumors
1. Osteoma is a benign lesion of bone that in many cases represent a developmental abnormaly or reactive growth rather than true neoplasms. They are most common in the head, including the paranasal sinuses.
Microscopically, there is a mixture of woven and lamellar bone. They may cause local mechanical problems (e.g., obstruction of a sinus cavity) and cosmetic deformities.
2. Osteoid Osteoma and Osteoblastoma
are benign neoplasms with very similar histologic features. Both lesions typically arise during the 2nd & 3rd decades. They are well-circumscribed lesions, usually involving the cortex. The central area of the tumor, termed the nidus, is characteristically radiolucent. Osteoid osteomas arise most often in the proximal femur and tibia, and are by definition less than 2 cm, whereas osteoblastomas are larger. Localized pain is an almost universal complaint with osteoid osteomas, and is usually relieved by aspirin. Osteoblastomas arise most often in the vertebral column; they also cause pain, which is not responsive to aspirin. Malignant transformation is rare unless the lesion is treated with radiation.
Gross features
• Both lesions are round-to-oval masses of hemorrhagic gritty tan tissue.
• A rim of sclerotic bone is present at the edge of both types of tumors.
Microscopic features
• There are interlacing trabeculae of woven bone surrounded by osteoblasts.
• The intervening connective tissue is loose, vascular & contains variable numbers of giant cells.
3. Osteosarcoma
This is “a bone-producing malignant mesenchymal tumor.” Excluding myeloma and lymphoma, osteosarcoma is the most common primary malignant tumor of bone (20%). The peak age of incidence is 10-25 years with 75% of the affected patients are younger than age 20 years; there is a second peak that occurrs in the elderly, usually secondary to other conditions, e.g. Paget disease, bone infarcts, and prior irradiation. Most tumors arise in the metaphysis of the long bones of the extremities, with 60% occurring about the knee, 15% around the hip, & 10% at the shoulder. The most common type of osteosarcoma is primary, solitary, intramedullary, and poorly differentiated, producing a predominantly bony matrix.
Gross features
• The tumor is gritty, gray-white, often with foci of hemorrhage and cystic degeneration.
• It frequently destroys the surrounding cortex to extend into the soft tissue.
• There is extensive spread within the medullary canal, with replacement of the marrow. However, penetration
of the epiphyseal plate or the joint space is infrequent.
Microscopic features
• Tumor cells are pleomorphic with large hyperchromatic nuclei; bizarre tumor giant cells are common, as are mitoses.
• The direct production of mineralized or unmineralized bone (osteoid) by malignant cells is essential for diagnosis of osteosarcoma. The neoplastic bone is typically fine, lace-like but can also be deposited in broad sheets.
• Cartilage can be present in varying amounts. When malignant cartilage is abundant, the tumor is called a chondroblastic osteosarcoma.
Pathogenesis
• Several genetic mutations are closely associated with the development of osteosarcoma. In particular, RB gene mutations that occur in both sporadic tumors, and in individuals with hereditary retinoblastomas. In the latter there are germ-line mutations in the RB gene (inherited).
• Spontaneous osteosarcomas also frequently exhibit mutations in genes that regulate the cell cycle including p53, cyclins, etc.
Osteosarcomas typically present as painful enlarging masses.
Radiographs usually show a large, destructive, mixed lytic and blastic mass with infiltrating margins. The tumor frequently breaks the cortex and lifts the periosteum. The latter results in a reactive periosteal bone formation; a triangular shadow on x-ray between the cortex and raised periosteum (Codman triangle) is characteristic but not specific of osteosarcomas.
Osteosarcomas typically spread hematogenously; 10% to 20% of patients have demonstrable pulmonary metastases at the time of diagnosis.
Glomerulonephritis
Characterized by inflammation of the glomerulus.
Clinical manifestations:
Nephrotic syndrome (nephrosis) → Most often caused by glomerulonephritis.
Laboratory findings:
(i) Proteinuria (albuminuria) and lipiduria—proteins and lipids are present in urine.
(ii) Hypoalbuminemia—decreased serum albumin due to albuminuria.
(iii) Hyperlipidemia—especially an increase in plasma levels of low-density lipoproteins and cholesterol.
Symptoms
severe edema, resulting from a decrease in colloid osmotic pressure due to a decrease in serum albumin.
Lysosomal (lipid) storage diseases
- Genetic transmission: autosomal recessive.
- This group of diseases is characterized by a deficiency of a particular lysosomal enzyme. This results in an accumulation of the metabolite, which would have otherwise been degraded by the presence of normal levels of this specific enzyme.
Diseases include:
Gaucher’s disease
(1) Deficient enzyme: glucocerebrosidase.
(2) Metabolite that accumulates: glucocerebroside.
(3) Important cells affected: macrophages.
Tay-Sachs disease
(1) Deficient enzyme: hexosaminidase A.
(2) Metabolite that accumulates: GM2 ganglioside.
(3) Important cells affected: neurons.
(4) Symptoms include motor and mental deterioration, blindness, and dementia.
(5) Common in the Ashkenazi Jews.
Niemann-Pick disease
(1) Deficient enzyme: sphingomyelinase.
(2) Metabolite that accumulates: sphingomyelin.
(3) Important cells affected: neurons.
Hepatitis B virus (“serum hepatitis”)
- Hepatitis B (HBV) may cause acute hepatitis, a carrier state, chronic active disease, chronic persistent disease, fulminant hepatitis, or hepatocellular carcinoma
- It is caused by a DNA virus, the virions are called Dane particles.
b. Incubation period: ranges from 4 to 26 weeks, but averages 6 to 8 weeks.
a. Symptoms last 2 to 4 weeks, but may be asymptomatic.
c. The hepatitis B viral structure has also been named the Dane particle.
Transmission is through contact with infected blood or other body fluids. It can be transmitted by sexual intercourse and is frequently transmitted to newborns of infected mothers by exposure to maternal blood during the birth process
- Associated antigens include core antigen (HBcAg) and surface antigen (HBsAg).
The latter is usually identified in the blood for diagnosis. HbsAg is the earliest marker of acute infection.
HBeAg is also associated with the core. Its presence indicates active acute infection; when anti-HBeAg appears, the patient is no longer infective
- HBV is associated with hepatocellular carcinoma; HBsAg patients have a 200-fold greater risk of hepatocellular carcinoma than subjects who have not been exposed.
Antibodies
- Antibodies to surface antigen (anti-HBs) are considered protective and usually appear after the disappearance of the virus.
-Antibodies to HBcAg are not protective. They are , detected just after the appearance of HBsAg and are used to confirm infection when both HBsAg and anti HBs are absent (window).
- Antibodies to HBeAg are associated with a low risk of infectivity.
d. Infection increases the risk for hepatocellular carcinoma.
e. Laboratory assay of hepatitis B antigens and antibodies:
(1) HBsAg—present only in acute infection or chronic carriers.
(2) HBsAb—detectable only after 6 months post-initial infection. HBsAb is present in chronic infections or vaccinated individuals. Note: HBsAb is also being produced during acute infections and in chronic carriers; however, it is not detectable via current laboratory methods.
(3) HBcAg—present in either acute or chronic infection.
(4) HBeAg—present when there is active viral replication. It signifies that the carrier is highly infectious.
(5) HBeAb—appears after HBeAg. It signifies that the individual is not as contagious.
f. Vaccine: contains HBsAg.
g. Prevention: immunoglobulins (HBsAb) are available.
THE PITUITARY GLAND
This is a small, bean-shaped structure that lies at the base of the brain within the confines of the sella turcica. It is connected to the hypothalamus by a "stalk," composed of axons extending from the hypothalamus. The pituitary is composed of two morphologically and functionally distinct components: the anterior lobe (adenohypophysis) and the posterior lobe (neurohypophysis). The adenohypophysis, in H&E stained sections, shows a colorful collection of cells with basophilic, eosinophilic or poorly staining ("chromophobic") cytoplasm.
Seborrheic keratosis
1. A round, brown-colored, flat wart.
2. Most often seen in middle-aged to older adults.
3. A benign lesion.
Hepatic failure
Etiology. Chronic hepatic disease (e.g., chronic active hepatitis or alcoholic cirrhosis) is the most common cause of hepatic failure although acute liver disease may also be responsible.
- Widespread liver necrosis may be seen with carbon tetrachloride and acetaminophen toxicity. Widespread steatosis is seen in Reye's syndrome, a cause of acute liver failure most often seen in children with a recent history of aspirin ingestion for an unrelated viral illness.
- Massive necrosis may also be seen in acute viral hepatitis, after certain anesthetic agents, and in shock from any cause.
Clinical features. Hepatic failure causes jaundice, musty odor of breath and urine, encephalopathy, renal failure (either by simultaneous toxicity to the liver and kidneys or the hepatorerial syndrome), palmar erythema, spider angiomas, gynecomastia , testicular atrophy