Clinical Pathology Quiz

ENTEROTOXIN produced by Staphylococcus aureus is an exotoxin responsible for the patient's condition. The clinical presentation and the laboratory findings are suggestive of staphylococcal food poisoning. A short incubation period (1-6 hours) with predominant emesis suggests Staphylococcal food poisoning. S. aureus organisms are Gram- positive cocci that occur in grape-like clusters being catalase and coagulase positive and forming golden yellow colonies on agar. Staphylococcal food poisoning results from ingestion of preformed enterotoxins on food contaminated with S. aureus. Enterotoxins produced by S. aureus elicit an emetic response. A total of 14 staphylococcal enterotoxins have been identified, including staphylococcal enterotoxin A (SEA), SEB, SEC, SED, SEE, SEG, SEH, SEI, SE], SEK, SEL, 5E1'4, SEN, and SEQ. Staphylococcal enterotoxins A through E have been implicated in staphylococcus gastroenteritis. These enterotoxins are heat stable and resistant. Bacteria growing in carbohydrates and meat products produce enterotoxins which, upon ingestion, diffuse into the circulation and cause emesis by stimulating the vomiting center in the central nervous system.
Leukocidin is a membrane damaging toxin expressed by S. aureus that acts on polymorphonuclear leukocytes.
ALPHA TOXIN or alpha hemolysin is the most potent membrane-damaging toxin of S. aureus and causes hemolysis.
Exfoliatin toxin (ET) elaborated by S. aureus causes scalded skin syndrome. This is manifested as widespread blistering and loss of the epidermis revealing a red base. ETA and ETB are the 2 antigenically distinct forms of the toxin. ET has esterase and protease activity, which targets a protein involved in maintaining epidermal integrity causing separation of the epidermis.
TOXIC SHOCK SYNDROME TOXIN (TSST-1) has superantigen activity and when expressed systemically it causes life threatening toxic shock syndrome. The clinical presentation includes fever, hypotension and diffuse macular erythema, with involvement of 3 or more of the organ systems (gastrointestinal, renal, hepatic, musculoskeletal, and nervous system).

The isolate from pus is Streptococcus pneumoniae, one of the common agents of community acquired pneumonia in children, and the penicillin resistance is due to alteration in the penicillin binding proteins (PBPs). Pleural empyema can occur as a complication especially in small children and the elderly.
PBPs are membrane-associated serine peptidases required for biosynthesis of peptidoglycan, an important constituent of bacterial cell wall. Penicillin has the ability to bind and inactivate the PEPs so that peptidoglycan synthesis is blocked. Of the 6 PEPs found in S,pneumoniae, PEPs la, 2b, and 2x are the major targets associated with activities of penicillin and some cephalosporirs. Pneumococcal resistance is attributed to alteration in these PBPs. The PEPs are under chromosomal control of the bacterium and low affinity variants may result by mutations in the strain. Altered PBPs can also occur as a result of recombination with foreign DNA sequences that code for low affinity PEPs in other pneurnococcal strains or closely related species. Low level resistance mainly depends or alterations in PEP 2x. High level resistance requires a combination of altered PEPs la, 2b, and 2x.
According to National Committee for Clinical Laboratory Standards (NCCL5), S. pneumoniae strains with MIC of 0.06 mcgiml are considered as susceptible, MIC of 0.1-1.0 mcg/ml as non-susceptible (intermediate resistance), and MIC of >2 mcg/ml as resistant to penicillin. Penicillin susceptible strains of S. pneumoniae are usually found to be susceptible to other antibiotic agents as well. Strains with high level resistance (MIC >8 mcg/ml) are likely to show resistance to cephalosporins, erythromycin, and trimethoprinn-sulfamethoxazole. Varcomycin and linezolid are useful for treating infections caused by multi-drug resistant strains.
Penicillin resistance in pneumococci is a worldwide problem. In the U.S. in the 1990s, incidence of infections due to penicillin resistant and multi drug resistant S. pneumoniae was high. Emergence of S. pneumoniae with very high level resistance (MIC of >8mcgiml) has also been documented. A 7-valent conjugate vaccine containing the 7 most common serotypes causing invasive infections in children (14, 6B, 19F, 18C, 23F, 4, and 9V) was licensed in the year 2000. It has helped in reducing the incidence of penicillin resistant pneumococcal infections. Serotypes 23F, 14, and 6E, to which most of the high-level-penicillin resistant strains belong, have been included in this vaccine. CDC recommends this vaccine for children under 5 years as it reduces colonization (nasopharyngeal carriage which acts as a source of transmission) and, prevents pneumococcal disease. This hepta-valent conjugate vaccine has the advantage of being immunogenic and protective even in children less than 2 years, unlike the 23-valent polysaccharide vaccine introduced earlier.
Recently, polymerase chain reaction (PCR)-based genotyping of PEP genes has been found to be a rapid and useful method to detect the genetic susceptibility of S. pneumoniae to beta-lactams.

PENICILLIN RESISTANCE BY THE PRODUCTION OF PLASMID-MEDIATED BETA LACTAMASE
is the mechanism commonly found in Staphylococcus aureus and gram-negative bacteria like N. gonorrheae and H. influenzae. Beta-lactamases hydrolyze the beta-lactam ring and abolish its activity. This type of resistance can be spread by bacteriophage-mediated transduction as in S. aureus or by conjugation as in some of the Gram-negative bacteria.

PRODUCTION OF CHROMOSOMALLY MEDIATED BETA-LACTAMASES cause development of penicillin resistance in anaerobic bacteria like Bacteroides fragilis and in various other Gram- negative bacilli. Several types of chromosomal beta-lactamases are described, which confer resistance to different beta-lactam antibiotics.

CHANGE IN PORIN CHANNELS leading to alteration in permeability is a mechanism of antibiotic resistance seer in Gram-negative bacteria. The outer membrane present in the cell wall of Gram-negative bacteria has channels containing protein molecules called porins which allow passive diffusion of small hydrophilic molecules across the membrane. Large molecules like antibiotics penetrate the outer membrane slowly. The membrane permeability is an important determinant of the intrinsic resistance of bacteria to antibiotics. In acquired resistance, loss or deficiency of specific porins reduce the outer membrane permeability and prevent the antibiotic from crossing the cell membrane. Deficiency in porin-outer membrane protein F (OmpF) has been shown to mediate beta-lactam resistance in Escherichia coll. Deficiency in OmpK35 and 0mp36 porins mediate beta-lactam resistance in Klebsiella pneumoniae. Loss or deficiency of porirs can augment resistance caused by beta-lactamase production. Antibiotic resistance can develop as a result of low
membrane permeability working synergistically with other mechanisms like active drug reflux or enzymatic degradation of the antibiotic.
EFFLUX PUMP
Bacterial genomes contain genes coding for multidrug efflux pumps. Active efflux is known to play a major role in the intrinsic as well as acquired drug resistance in various bacterial species. The active efflux pump of the bacterium forces the antibiotic, which crosses the cell membrane out of its cytoplasm so that the concentration of the drug is too low to be effective.
Over production of efflux pumps or acquisition of pump genes from extraneous sources often result in increased level of resistance. Efflux pumps have been identified in S. pneumoniae that contribute to the development of fluoroquinolone resistance. The major mechanism of tetracycline resistance in Gram-negative bacteria has been recognized as being due to drug-specific efflux.
This mechanism often contributes to resistance of a bacterium to more than one antibiotic. Different quinoline derivatives have been successfully used as efflux-pump inhibitors. These drugs have been shown to block the efflux pump mechanism and restore drug susceptibility to multi-drug resistant clinical isolates of Gram-negative bacteria.

A commensal or symbiotic relationship has been observed between Prevotella bivia and G.vaginalis. P,bivia and P.disiensis are known to be associated with upper genital tract infections such as tuba-ovarian and pelvic abscesses in women. Together with other bacterial species, P.bivia has been isolated from various lesions like perirectal abscesses, septic arthritis, intracranial abscess, endocarditis, infected wounds, and paronychia. Based on experiments in animal models, it is suggested that P.bi via in conjunction with an aerobic organism can be more pathogenic.
Molecular methods have been found useful for identification of the different bacterial species associated with By including Prevotella.
Other prevotelia species like P.melaninogenicus that occur as oral indigenous flora are found to be associated with endogenous periodontal and pulmonary infections.
Bacterial vaginosis (BV) is a Lower genital tract syndrome that affects women of reproductive age. Though the pathogenesis of BV is not well understood, microbes associated with BV mostly belong to endogenous flora of the vagina. G.vaginalis is considered the predomonant bacterial species associated with BV. By is associated with increased risk of obstetric and gynecological complications and acquisition of HIV and other STDs.
Commensals of the genital tract of healthy females include aerobic and anaerobic bacteria, with predominance of Lactobacillus. In BY, the Lactobacillus that produces H202 is depleted and is replaced by overgrowth of aerobic and anaerobic flora, including Gardnerella vaginal/s. Mobiluncus curtisii, Mycoplasma hominis, and Prevotella bivia.
Lactobacillus and Prop/on/bacterium, though anaerobes, are Gram-positive bacilli, and Prop/on/bacterium is a commensal of skin. Mycoplasma and Gardnerella are not obligate anaerobes. Therefore, the possibility of the isolates belonging to these 4 genera is excluded.
Mobiluncus species are obligate anaerobes and are known to be associated with By. But they are curved motile bacilli and often appear Gram-variable. Prevotella species are obligately anaerobic non-motile Gram-negative bacilli. They are saccharolytic and high percentage of the strains produce beta-lactamase. So the anerobic bacterial species referred to in the question is likely to belong to the genus Prevotella.

The correct answer is spherules with endospores. This patient has pneumonia with a travel history to the Southwest (New Mexico), and erythema nodosum, which is characteristic of Coccidioides. When the soil is disrupted, the arthroconidia can become airborne and, if inhaled by a susceptible host, produce infection. Localized in the pulmonary acinus, the arthrospore sheds its outer coating, swells, and becomes a spherical structure, i.e. the spherule.
Broad based budding is seen in Blastomycosis.
Tuberculate macroconidium is seen in Histoplasmosis. Histoplasmosis is more common in the Ohio River Valley.
This patient does not have a bacterial infection. The patient has a dry cough, with a fever, pleuritic chest pain, as well as a travel history to an endemic area of Coccidioides.

The common bacterial agents associated with NGU are Chlamydia trachomatis, genital Mycoplasmas, and Ureaplasmas. Of these, C.trachomatis is a strict intracellular organism and does not grow on inanimate media.
Ureaplasma and mycoplasma are fastidious organisms. They can be differentiated and identified to genus level by their colony characteristics on AS selective medium. The isolate from the urethral discharge has the colony characteristics typical of Ureaplasma. Ureaplasma was known as 'T-strain mycoplasmal earlier because it produces tiny colonies (T for tiny). THE BACTERIUM PRODUCES UREASE ENZYME, which hydrolyzes urea and liberates ammonia. Urea is provided in A8 agar and the brown color of ureaplasma colonies is due to the activity of urease enzyme in presence of calcium chloride contained in the medium. Urease is considered as a potential virulence factor of ureaplasma. Urea is an essential growth factor and urea hydrolysis is the predominant means by which the organisms generate ATP.
Mycoplasma colonies are larger measuring 200-300 microns in diameter with typical fried egg appearance.
The isolate being Ureaplasma sp, does not possess the other characteristics listed. Like mycoplasma, it lacks a rigid cell wall and is bounded by a triple-layered cell membrane containing sterols. Sterol is not inhibitory, but essential for the growth of ureaplasma.
Beta-lactam antibiotics act by inhibiting cell wall synthesis. Ureaplasma is not susceptible to beta-lactams as it does not possess a cell wall. LPS is an integral part of the cell wall of Gram-negative bacteria and is not found in ureaplasma.
L-forms of bacteria can revert back to their parental bacterial forms under favorable environment, by synthesizing cell wall peptidoglycan. Ureaplasma does not produce cell wall under any circumstances and are not related to L- forms of bacteria.
The 2 species of genital ureaplasmas, Ureaplasma urealyticum and Ureaplasma parvum, colonize on human mucosal surfaces as commensals. Both species, particularly U.urealyicum, are potentially pathogenic. U.urealyticum is recognized as an important causative agent of NGU and could be associated with persistent and recurrent urethritis. Maternal genital colonization with U.urealyticum can lead to chorioamnionitis and promote preterm delivery. Ureaplasmas are associated with neonatal and perinatal infections like pneumonia and meningitis in premature and low birth weight infants. Respiratory colonization of such infants by the organisms has been reported to increase the risk of developing bronchopulmonary dysplasia (BPD). Ureaplasma sp have also been linked to male infertility and to formation of struvite stones in the urinary tract. Stone formation is considered to be mediated by the urease activity of these bacteria.
Polymerase chain reaction assays targeting different genes (16S rRNA gene, urease gene, and MBA gene) have been developed for detecting ureaplasmas in clinical specimens and for distinguishing the 2 species. The tests are reported to have high specificity and sensitivity.

In 1928, an English bacteriologist named Frederick Griffith published the results of the experiment described above. While the results were curious and unusual in 1928, this experiment became a classic example of the genetic event now known as transformation. In transformation, soluble DNA from a donor cell (in this case the dead S strain) is taken up by a recipient cell of the same species but a different genotype (in this case the R strain). The DNA from the donor recombines with the DNA of the recipient resulting in the expression of genetic characteristics of the donor (in this case, the ability to manufacture capsular material).
Conjugation and transduction are also important mechanisms of DNA transfer but soluble DNA is not involved in these processes. Transportation and transposition are unrelated to the genetic events described above.
2 Corinthians 3:18 - ASV
But we all, with unveiled face beholding as in a mirror the glory of the Lord, are TRANSFORMED into the same image from glory to glory, even as from the Lord the Spirit.

Bacterial vaginosis ("nonspecific vaginitis") is a disease that is characterized by a malodorous vaginal discharge. The diagnosis of bacterial vaginosis is based on the presence of at least three of four of the following signs; 1) a characteristic homogeneous gray discharge; 2) the presence of "clue" cells; 3) a vaginal pH greater than 4.5; 4) the release of a fishy amine odor from vaginal secretions mixed with 10% potassium hydroxide (KOH).
GONORRHEA CERVICITIS is caused by Neisseria gonorrhoeae and is a common sexually transmitted disease. Clinical manifestations include vaginal discharge, dysuria, internnenstrual bleeding, purulent or mucopurulent endocervical discharge, and erythema. Many women have mild or symptomatic infections. The organism is a gram-negative cliplococci that is oxidase positive, glucose positive, sucrose negative, ONPG negative, and nitrate negative. When a gram-negative diplococci is detected in the gram stained smear of discharge material, it is not diagnostic for woman of Neisseria gonorrhoeae because there are other normal gram-negative clIplococcl present in the vaginal tract that are part of the normal flora. DNA probes, culture with biochemical identification, and EIA methods are used to detect and identify the organism.
CANDID IASIS/VULVOVAGINITIS is often a chronic disease and is the most common candida infection. Candida
albicans is the most common candida species causing candidiasis. The disease causes an intense vaginal itching and burning sensation that is accompanied by a pruritus. There is usually a discharge that is described as thick and curd -like. The vulva is inflamed and ulcerations can occur. Gram stains of the discharge will typically contain large amounts of yeast cells.
CHLAMYDIAL ENDOCERVICITIS is a mucopurulent infection caused by Chlamydia trachomatis. It is a sexually transmitted disease. The organism cannot be detected by normal gram staining methods and requires fluorescent antibody staining techniques, cell culture, DNA probes, or EIA methods to detect it. It is the most common sexually transmitted pathogen. The organism also causes urethritis, endometritis, salpingitis, tubal factor infertility, and ectopic pregnancy.
TRICHOMONIASIS is caused by Trichomonas vaginalis, a flagellated protozoan. It is characterized by vaginal itch-01g and discomfort with a discharge that is many times copious, frothy, and malodorous. Person to person spread is primarily through sexual contact. There is severe itching of the vulva and inner thighs. Definitive diagnosis is made by demonstrating the motile organisms in fresh secretions, or it can also be demonstrated in spun down urine during a urinalysis.

Krukenberg tumors are metastatic tumors in the ovaries. There are signet-ring cells found in the ovaries. Metastasis from the stomach is most often the cause of Krukenberg tumors.
Brenner tumors are ovarian neoplasms of epithelial cells within a stroma. Brenner tumors are made of transitional cell epithelial nests, similar to bladder epithelium. The majority are benign.
A teratoma is of germ-cell origin.
Arrhenoblastoma is also known as a Sertoli-Leydig cell tumor. A hilus cell tumor is a pure Leydig cell tumor.

Gestational trophoblastIc disease constitutes a spectrum of tumor and tumor like conditions characterized by proliferation of pregnancy associated trophoblastic tissue of progressive malignant potential. The lesions include: Hydatidifornn mole - complete Hydatidiform mole -partial Invasive mole Choriocarcinoma Placental site trophoblastic tumor Hydatidiform mole is characterized by cystic swelling of the chorionic villi, accompanied by variable trophoblastic proliferation. The moles can occur at any age during active reproductive life, but the risk is higher in pregnant females in their teens or between the ages of 40 and 50 years. In most instances, the moles develop within the uterus, but they may occur in any ectopic site of pregnancy. This is further divided into complete type and partial type based on histologic, cytogenetic and flow cytometric studies.
In most instances, the moles develop within the uterus, but they may occur in any ectopic site of pregnancy. When discovered, generally in the 4th or 5th month of pregnancy, the uterus is larger than the expected size for the duration of pregnancy. Most patients present with vaginal bleeding and passage of small grape-like masses. Ultrasound examination shows the typical snowstorm appearance and is diagnostic in most of the cases. The level of human chorionic gonadotrophin greatly exceeds that produced by normal pregnancy of similar period. Many studies have shown that 80-90% remain benign, 10% develop into invasive moles and 2.5% into choriocarcinoma.
INVASIVE MOLE   is defined as a mole that penetrates and even perforates the uterus. There is invasion of the myometrium by hydropic chorionic villi, accompanied by proliferation of both the cytotrophoblasts and syncytiotrophoblasts. The tumor is locally destructive and invades the parametrial tissue and blood vessels. Hydropic villi may ennbolize to distant sites, such as lungs and brain, but do not grow in these organs as true metastases. It manifests clinically as vaginal bleeding and irregular enlargement of the uterus. It is always associated with persistent elevated chorionic gonadotrophin level and varying degrees of the luteinization of the ovaries. The tumor responds well to chemotherapy. Although benign, the rupture of the uterus will lead to hemorrhage.
CHORIOCARCINOMA  is an epithelial malignant neoplasm of trophoblastic cells derived from any form of previously normal or abnormal pregnancy. Although most cases arise in the uterus, ectopic pregnancies provide extrauterine sites of origin. Choriocarcinoma is a rapidly growing, widely metastasizing malignant neoplasm, but once it is identified, it responds well to chemotherapy. It is preceded by several conditions; 50 % arise in hydaticliform moles, 25% in previous abortions, and 22%, in normal pregnancies and the rest in ectopic pregnancies and genital and extragenital teratomas.
The choriocarcinoma is classically a soft, fleshy, yellow white tumor with a marked tendency to form large pale areas of ischennic necrosis, foci of cystic softening, and extensive hemorrhage. Histologically, it is a purely epithelial cellular malignancy that does not produce chorionic villi and that grows by abnormal proliferation of cytotrophoblasts and syncytiotrophoblasts. The tumor invades the underlying myometrium, frequently penetrates blood vessels and lymphatics, and in some cases extends into the uterine serosa and adjacent structures. In fatal cases, the metastases are found in the lungs, brain, bone marrow, liver, and other organs. They generally present with foul smelling bloody brown discharge. The human chorionic gonadotrophin levels are elevated to the levels above those encountered in hydatidiform moles. The results of chemotherapy for gestational choriocarcinoma are spectacular and they have resulted in up to 100% cure or remssion in all patients except some whom had high-risk metastatic trophoblastic disease.
PLACENTAL SITE TROPHOBLASTIC TUMOR  is a rare tumor characterized by proliferation of trophoblastic cells penetrating deep into the nnyometrium by intermediate trophoblastic cells. These cells are mononuclear and larger than cytotrophoblasts and have abundant cytoplasm. In contrast to the syncytiotrophoblasts, which produces human chorionic gonadotrophin, these cells are immune reactive to human placental lactogen. They are characterized by the absence of cytotrophoblasts and low levels of human chorlonic gonadotrophin. They are locally infiltrating but rarely may cause metastasis.

SEROUS CYSTADENOMA of the ovary are benign tumors containing clear, watery serous fluid. They are seen commonly between 20 to 50 years of age. Grossly, they are large and spherical masses. The small masses are generally unilocular but the larger may be multiloculated. The inner surface is smooth and glistening. They are characteristically lined by properly -oriented low columnar epithelium, which is sometimes ciliated and resembles tubal epithelium. Microscopic papillae may be found.
MUCINOUS CYSTADENOMAS are less common compared to the serous tumors and are generally seen in middle adult life. Grossly, they produce larger cystic masses, are multiloculatecl, and contain sticky gelatinous fluid rich in glycoproteins. Microscopically, they are characterized by a lining of tall columnar epithelial cells with apical mucin and the absence of cilia.
CYSTIC CORPUS LUTEA are normally present in the ovary.These cysts are lined by a rim of bright yellow luteal tissue containing luteinizing granulosa cells. They occasionally rupture and cause peritoneal reaction.
POLYCYSTIC OVARIAN DISEASE is characterized by numerous cystic follicles and when this is associated with ollgomenorrhea, the clinical term Stein-Leventhal syndromeis applied. These patients have persistent anovulation, obesity, hirsutism, and rarely virilism. The ovaries are usually twice the normal size, gray white with a smooth outer cortex and are studded with subcortical cysts 0.5 to1.5 cms in diameter. Microscopically, there is thickened superficial cortex beneath which are innumerable follicle cysts with hyperplasia of the theca interna. Corpus lutea are frequently absent.
DERMOID CYST is the clinical term applied to the mature teratoma and it is cystic in nature. These neoplasms are invariably benign and are derived from the ectodermal differentiation of totipotential cells. Cystic teratomas are generally found in young females during active reproductive years. They are bilateral in 15% of the cases. Grossly, they are unilocular cysts filled with hair and cheesy sebaceous material. On section, they reveal a thin wall lined by an opaque gray white wrinkled epidermis and hair shafts protruding from this frequently. Within this wall, there may be tooth like structures and areas of calcification. Microscopically, the cyst wall is composed of stratified squamous epithelium with underlying sebaceous glands, hair shafts, and other skin adnexal structures. All types of tissues derived from other germ layers may be seen, such as cartilage, bone, thyroid tissue and other various types of epithelium. About 1% may undergo malignant transformation of any one of the component elements, most commonly being squannous cell carcinoma.

SEROUS CYSTADENOMA of the ovary are benign tumors containing clear, watery serous fluid. They are seen commonly between 20 to 50 years of age. Grossly, they are large and spherical masses. The small masses are generally unilocular but the larger may be multiloculated. The inner surface is smooth and glistening. They are characteristically lined by properly -oriented low columnar epithelium, which is sometimes ciliated and resembles tubal epithelium. Microscopic papillae may be found.
MUCINOUS CYSTADENOMAS are less common compared to the serous tumors and are generally seen in middle adult life. Grossly, they produce larger cystic masses, are multiloculatecl, and contain sticky gelatinous fluid rich in glycoproteins. Microscopically, they are characterized by a lining of tall columnar epithelial cells with apical mucin and the absence of cilia.
CYSTIC CORPUS LUTEA are normally present in the ovary.These cysts are lined by a rim of bright yellow luteal tissue containing luteinizing granulosa cells. They occasionally rupture and cause peritoneal reaction.
POLYCYSTIC OVARIAN DISEASE is characterized by numerous cystic follicles and when this is associated with ollgomenorrhea, the clinical term Stein-Leventhal syndromeis applied. These patients have persistent anovulation, obesity, hirsutism, and rarely virilism. The ovaries are usually twice the normal size, gray white with a smooth outer cortex and are studded with subcortical cysts 0.5 to1.5 cms in diameter. Microscopically, there is thickened superficial cortex beneath which are innumerable follicle cysts with hyperplasia of the theca interna. Corpus lutea are frequently absent.
DERMOID CYST is the clinical term applied to the mature teratoma and it is cystic in nature. These neoplasms are invariably benign and are derived from the ectodermal differentiation of totipotential cells. Cystic teratomas are generally found in young females during active reproductive years. They are bilateral in 15% of the cases. Grossly, they are unilocular cysts filled with hair and cheesy sebaceous material. On section, they reveal a thin wall lined by an opaque gray white wrinkled epidermis and hair shafts protruding from this frequently. Within this wall, there may be tooth like structures and areas of calcification. Microscopically, the cyst wall is composed of stratified squamous epithelium with underlying sebaceous glands, hair shafts, and other skin adnexal structures. All types of tissues derived from other germ layers may be seen, such as cartilage, bone, thyroid tissue and other various types of epithelium. About 1% may undergo malignant transformation of any one of the component elements, most commonly being squannous cell carcinoma.

SAME EXPLANATION AS ABOVE

There is an association between cigarette smoking and the development of cervical cancer. There is no relationship between the age of menarche and the development of cervical cancer.
Multiparous women have an increased risk of cervical cancer. Thus, a woman who has never had children is not at increased risk of developing cervical cancer.
Picornavirus is a single strand RNA virus. It is not associated with cervical cancer. Cervical cancer is associated with infection with different subtypes of human papillomavirus (HPV).
Multiple sexual partners increase the risk of exposure to human papilloma virus; thus abstinence is not a risk factor. There is a very low occurrence of cervical cancer in virgins and nuns.

Gestational trophoblastIc disease constitutes a spectrum of tumor and tumor like conditions characterized by proliferation of pregnancy associated trophoblastic tissue of progressive malignant potential. The lesions include: Hydatidifornn mole - complete Hydatidiform mole -partial Invasive mole Choriocarcinoma Placental site trophoblastic tumor Hydatidiform mole is characterized by cystic swelling of the chorionic villi, accompanied by variable trophoblastic proliferation. The moles can occur at any age during active reproductive life, but the risk is higher in pregnant females in their teens or between the ages of 40 and 50 years. In most instances, the moles develop within the uterus, but they may occur in any ectopic site of pregnancy. This is further divided into complete type and partial type based on histologic, cytogenetic and flow cytometric studies.
In most instances, the moles develop within the uterus, but they may occur in any ectopic site of pregnancy. When discovered, generally in the 4th or 5th month of pregnancy, the uterus is larger than the expected size for the duration of pregnancy. Most patients present with vaginal bleeding and passage of small grape-like masses. Ultrasound examination shows the typical snowstorm appearance and is diagnostic in most of the cases. The level of human chorionic gonadotrophin greatly exceeds that produced by normal pregnancy of similar period. Many studies have shown that 80-90% remain benign, 10% develop into invasive moles and 2.5% into choriocarcinoma.
INVASIVE MOLE   is defined as a mole that penetrates and even perforates the uterus. There is invasion of the myometrium by hydropic chorionic villi, accompanied by proliferation of both the cytotrophoblasts and syncytiotrophoblasts. The tumor is locally destructive and invades the parametrial tissue and blood vessels. Hydropic villi may ennbolize to distant sites, such as lungs and brain, but do not grow in these organs as true metastases. It manifests clinically as vaginal bleeding and irregular enlargement of the uterus. It is always associated with persistent elevated chorionic gonadotrophin level and varying degrees of the luteinization of the ovaries. The tumor responds well to chemotherapy. Although benign, the rupture of the uterus will lead to hemorrhage.
CHORIOCARCINOMA  is an epithelial malignant neoplasm of trophoblastic cells derived from any form of previously normal or abnormal pregnancy. Although most cases arise in the uterus, ectopic pregnancies provide extrauterine sites of origin. Choriocarcinoma is a rapidly growing, widely metastasizing malignant neoplasm, but once it is identified, it responds well to chemotherapy. It is preceded by several conditions; 50 % arise in hydaticliform moles, 25% in previous abortions, and 22%, in normal pregnancies and the rest in ectopic pregnancies and genital and extragenital teratomas.
The choriocarcinoma is classically a soft, fleshy, yellow white tumor with a marked tendency to form large pale areas of ischennic necrosis, foci of cystic softening, and extensive hemorrhage. Histologically, it is a purely epithelial cellular malignancy that does not produce chorionic villi and that grows by abnormal proliferation of cytotrophoblasts and syncytiotrophoblasts. The tumor invades the underlying myometrium, frequently penetrates blood vessels and lymphatics, and in some cases extends into the uterine serosa and adjacent structures. In fatal cases, the metastases are found in the lungs, brain, bone marrow, liver, and other organs. They generally present with foul smelling bloody brown discharge. The human chorionic gonadotrophin levels are elevated to the levels above those encountered in hydatidiform moles. The results of chemotherapy for gestational choriocarcinoma are spectacular and they have resulted in up to 100% cure or remssion in all patients except some whom had high-risk metastatic trophoblastic disease.
PLACENTAL SITE TROPHOBLASTIC TUMOR  is a rare tumor characterized by proliferation of trophoblastic cells penetrating deep into the nnyometrium by intermediate trophoblastic cells. These cells are mononuclear and larger than cytotrophoblasts and have abundant cytoplasm. In contrast to the syncytiotrophoblasts, which produces human chorionic gonadotrophin, these cells are immune reactive to human placental lactogen. They are characterized by the absence of cytotrophoblasts and low levels of human chorlonic gonadotrophin. They are locally infiltrating but rarely may cause metastasis.