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General Pathology

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.

Keloids
1. Characterized by a progressively enlarging scar.
2. Caused by an abnormal accumulation of collagen at the site of injury.
3. More common in African-Americans.

Keratoses (Horny Growth)
1. Seborrheic keratosis
is a common benign epidermal tumor composed of basaloid (basal cell-like) cells with increased pigmentation that produce a raised, pigmented, "stuck-on" appearance on the skin of middle-aged individuals.
 - they can easily be scraped from the skin's surface.
 - frequently enlarge of multiply following hormonal therapy.
 - sudden appearance of large numbers of Seborrheic keratosis is a possible indication of a malignancy of the gastrointestinal tract (Leser-Trelat sign).

 2. An actinic keratosis is a pre-malignant skin lesion induced by ultraviolet light damage.
 - sun exposed areas.
 - parakeratosis and atypia (dysplasia) of the keratinocytes.
 - solar damage to underlying elastic and collagen tissue (solar elastosis).
 - may progress to squamous carcinoma in situ (Bowen's disease) or invasive cancer.

 3. A keratoacanthoma is characterized by the rapid growth of a crateriform lesion in 3 to 6
weeks usually on the face or upper extremity.
 - it eventually regresses and involutes with scarring.
 - commonly confused with a well-differentiated squamous cell carcinoma. 

Pheochromocytoma

Pheochromocytomas are neoplasms composed of chromaffin cells, which as their normal counterparts synthesize and release catecholamines. 

1. Arise in association with one of several familial syndromes such as MEN syndromes, type 1 neurofibromatosis, von Hippel-Lindau disease, and Sturge-Weber syndrome. 
2. Are extra-adrenal, occurring in sites such as the organ of Zuckerkandl and the carotid body, where they are usually called paragangliomas rather than pheochromocytomas. 
3. Are bilateral; but in association with familial syndromes, this figure may rise to 50%. 
4. Are malignant; frank malignancy, however, is more common in extra-adrenal tumors.  

Gross features

- The size of these tumors is quite variable ranging from small to huge masses. 
- Sectioning shows yellow-tan, well-defined tumor that compress the adjacent adrenal. Large lesions display areas of hemorrhage, necrosis, and cystic degeneration.  
- Incubation of the fresh tissue with potassium dichromate solutions converts the tumor a dark brown color.

Microscopic features
- These tumors are composed of polygonal to spindle-shaped chromaffin cells and their supporting sustentacular cells, arranged in well-defined small nests (Zellballen)," rimmed by a rich vascular network.
- The cytoplasm is often finely granular (catecholamine-containing granules) 
- The nuclei are often quite pleomorphic. 
- Both capsular and vascular invasion may be encountered in benign lesions, and the presence of mitotic figures per se does not imply malignancy. Therefore, the definitive diagnosis of malignancy in pheochromocytomas is based exclusively on the presence of metastases. These may involve regional lymph nodes as well as more distant sites, including liver, lung, and bone. 

The laboratory diagnosis of pheochromocytoma is based on demonstration of increased urinary excretion of free catecholamines and their metabolites, such as vanillylmandelic acid (VMA)&  metanephrines.

Seborrheic dermatitis is a scaly dermatitis on the scalp (dandruff) and face.
 - due to Pitysporium species
 - can be seen in AIDS as an opportunistic infection

Actinic keratosis
1. Dry, scaly plaques with an erythematous base.
2. Similar to actinic cheilosis, which occurs along the vermilion border of the lower lip.
3. Caused by sun damage to the skin.
4. Dysplastic lesion, may be premalignant.

Mycobacterium leprae 

- tuberculoid type has intact cellular immunity
 - forms granulomas and kill the organisms (very few present).
 - evokes a positive lepromin skin test
 - localized skin lesions that lack symmetry
 - nerve involvement (organisms invade Schwann cells) that dominates the clinical picture and leads to skin anesthesia, muscle atrophy and autoamputation.
 - lepromatous leprosy patients lack cellular immunity
 - no granulomas
 - organisms readily identified
 - negative lepromin skin test
 - Bacteremia disseminates to cooler areas like the digits.
 - symmetrical, skin lesions that produce the classic leonine facies; biopsy reveals grentz zone in superficial dermis and then organisms in macrophages.
 - neural involvement is a late feature of the disease.
 - lepromin skin test is to determine host immunity; not a diagnostic test.
 - treatment: dapsone + rifampin

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