Repro USMLE step 1 9-6 (9)

Question 1

This patient is young and has no symptoms. She presents for a routine gynecologic examination, and a discrepancy is found in the size of the ovaries. Ultrasound reveals an incidental ovarian mass. This is the general presentation of a Brenner tumor, which is?

Answer 1

a benign ovarian tumor composed of cells that resemble bladder transitional epithelium.

The classic biopsy specimen of a Brenner tumor, as shown in the image, reveals nests of transitional cells (identified by the circles) with coffee bean–shaped nuclei among a fibrous stroma. Epithelial tumors comprise 85% of ovarian tumors, with serous epithelial tumors being the most common epithelial tumor and Brenner tumors being the least common. Other types of epithelial tumors include mucinous, endometrioid, clear cell/mesonephric, and mixed subtypes.

Question 2

This patient has no symptoms, so some of the other answer options would be incorrect because they are associated with specific symptoms. Meigs syndrome, which is characterized by the classic triad of fibroma, ascites, and hydrothorax, is seen with ovarian fibromas. Ovarian mucinous cystadenomas are associated with a unilateral, multilocular ovarian mass. They can cause bloating, increase in waist size, weight gain, and abdominal pain. Tumors associated with arrhythmias refer to struma ovarii, which can cause symptoms of hyperthyroidism including heat intolerance, tachycardia, diarrhea, and tremor. Tumors that secrete estrogen refer to granulosa cell tumors, which can cause?

Answer 2

endometrial hyperplasia and endometrial carcinomas. Ultrasound examination of this patient did not reveal any endometrial abnormalities.

Question 3

Brenner tumors are benign ovarian tumors composed of cells that resemble bladder transitional epithelium. They are not as common (or as commonly tested) as?

Answer 3

serous epithelial tumors.

Question 4

This patient presents with severe abdominal cramping, menorrhagia, and lower back pain correlating with her menstrual cycle. Her symptoms, which have not responded to treatment with oral contraceptives, are classic for endometriosis. Diagnosis would be confirmed by biopsy of the ovarian lesions showing ectopic endometrium.

Ectopic endometrium is estrogen-dependent. Sex hormones are generally produced in response to follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which are controlled by physiologic pulsatile secretion of gonadotropin-releasing hormone (GnRH). Treatment with GnRH agonists like leuprolide or goserelin removes this physiologic pulsation and actually decreases LH/FSH secretion after a short stimulatory period, thereby inhibiting growth of endometrial tissue.
Major adverse effects of GnRH-induced sex hormone depletion include?

Answer 4

osteoporosis and pseudo-menopause (night sweats, hot flashes, etc). Although GnRH agonists are more commonly used, danazol, a synthetic androgen, can also be used to treat endometriosis, Of note, when the ovaries are involved in endometriosis, disease is seen bilaterally in approximately one third of cases.

Question 5

Heart failure can be an adverse effect of trastuzumab, a monoclonal antibody used to treat HER2-positive breast cancer. Hyperkalemic metabolic acidosis may occur in patients taking spironolactone, a diuretic that is used to treat high blood pressure, heart failure, and edema. (This drug may also be used off-label to treat hirsutism in women with polycystic ovarian syndrome.) Increased uterine cancer risk is seen with estrogen-only supplementation, which may be taken to alleviate?

Answer 5

menopause-related symptoms. Stevens-Johnson syndrome is one adverse effect of aromatase inhibitors, used in the treatment of breast cancer in postmenopausal women.

Question 6

GnRH agonists such as leuprolide or goserelin can be used for treatment of endometriosis-related pelvic pain. They act by decreasing LH/FSH secretion after a short stimulatory period. Adverse effects of sex hormone depletion include?

Answer 6

osteoporosis and pseudo-menopause. Danazol can also be used to treat endometriosis, but GnRH agonists are more commonly used.

Question 7

A woman presents to the physician’s office with red, ring-like lesions on her body that appeared after using the yoga mats at her local gym.
Given these findings, the most likely diagnosis is tinea corporis, commonly known as “ringworm.” Tinea corporis is a fungal skin infection that is seen in athletes who play close-contact sports or use improperly cleaned sports equipment (in this case, yoga mats). Lesions are pruritic, erythematous, scaly, and demonstrate central clearing.
Mild tinea corporis can be treated with topical antifungals, but systemic therapy, such as ?

Answer 7

ketoconazole, is preferred for more extensive skin involvement. Ketoconazole acts by blocking the formation of fungal membrane steroids.

In addition, the drug inhibits the enzymes desmolase/CYP450scc and 17-a-hydroxylase. Inhibition of 17-a-hydroxylase contributes to ketoconazole’s antiandrogenic effects, which include decreased libido, impotence, and gynecomastia in men. This patient’s darkening skin is a result of the desmolase inhibition. Desmolase is necessary for adrenal production of testosterone and cortisol. Free cortisol is responsible for feedback inhibition of the POMC gene, which codes for synthesis of ACTH, lipotropin, melanocyte-stimulating hormone, and some endogenous endorphins. With decreased cortisol levels, this feedback inhibition is removed and the POMC gene products are freely transcribed. This, in turn, leads to excessive melanocyte-stimulating hormone which can cause increased integumentary pigmentation, similar to the hyperpigmentation seen in Addison disease and which is seen in the darkened patches on this patient’s skin.

Question 8

Amphotericin B and flucytosine are not used in the treatment of tinea corporis. Both fluconazole and itraconazole are not associated with?

Answer 8

endocrine side effects and would not cause the skin darkening seen with ketoconazole.

Question 9

Desmolase inhibition by ketoconazole results in reduced levels of circulating adrenal steroid hormones. Without free cortisol to feedback-inhibit ACTH, POMC gene products including melanocyte-stimulating hormone are freely transcribed; this leads to the skin darkening sometimes seen with?

Answer 9

ketoconazole use.

Question 10

This young child has significant hepatosplenomegaly and progressive widespread neurodegeneration (as evidenced by his failure to hit developmental milestones). Fundoscopic examination shows a cherry-red spot on the macula (first image). The combination of these symptoms and findings suggest a diagnosis of Niemann-Pick disease.

Niemann-Pick disease is caused by the absence of the enzyme sphingomyelinase which converts ?

Answer 10

sphingomyelin to ceramide. The deficiency of sphingomyelinase in patients with Niemann-Pick disease causes accumulation of sphingomyelin and cholesterol in parenchymal and reticuloendothelial cells. Under a light microscopy, these lipid-laden macrophages have a foamy appearance, which is consistent with the findings on the bone marrow biopsy examination. The foamy appearance is caused by the presence of innumerable small vacuoles of relatively uniform size.

Question 11

Fabry disease is caused by a mutation of a-galactosidase A which converts ceramide trihexoside to lactosyl cerebroside. It manifests in early childhood with peripheral neuropathy, angiokeratomas (tiny painless papules), renal insufficiency and cardiovascular disease (not seen in our patient).

Krabbe disease is caused by a mutation in galactocerebrosidase which converts ?

Answer 11

galactocerebroside to ceramide. Patients with this disease develop optic atrophy (not a cherry-red macula spot), peripheral neuropathy, and developmental delay.

Question 12

Tay-Sachs disease and Niemann-Pick have a similar clinical presentation of progressive neurological decay with a cherry-red spot on the macula. Tay-Sachs is caused by a lack of ß-hexosaminidase A which converts ganglioside M2 to ganglioside M3. The key distinguishing feature is the lack of hepatosplenomegaly in Tay-Sachs disease.

Lastly, Gaucher disease is caused by?

Answer 12

a lack of ß-glucocerebrosidase which converts glucocerebroside to ceramide. While patients with Gaucher disease may have hepatosplenomegaly, the other symptoms of skeletal weakness, pathologic fractures and bruising (because of thrombocytopenia) are absent in this patient.

Question 13

Niemann-Pick disease is caused by a lack of the enzyme sphingomyelinase which converts ?

Answer 13

sphingomyelin to ceramide. It is characterized by neurodegeneration, a cherry-red spot on the macula, foam cells, and notably, hepatosplenomegaly (which distinguishes this disease from Tay-Sachs disease).

Question 14

This sexually active patient with a painless ulcerative lesion on his penis most likely has primary syphilis caused by Treponema pallidum. Venereal Disease Research Laboratory (VDRL) titers and fluorescent treponemal antibody absorption (FTA-ABS) testing may be used to confirm the diagnosis.
Syphilis is categorized by the following stages:

Primary syphilis: In men, this stage is characterized by?

Answer 14

a painless chancre, usually on the penis, which develops about 3 weeks after exposure. Women with primary syphilis may appear to be free of symptoms because the chancre may develop in the vagina or rectum.

Question 15

Secondary syphilis: This disseminated stage of the disease develops within 4 to 10 weeks after primary infection and may manifest with a maculopapular rash, condyloma lata, lymphadenopathy, hair loss, muscle aches, fever, sore throat, and swollen lymph nodes. A latent, asymptomatic stage may follow and last for years.

Tertiary syphilis develops late in about 40% of patients who have gone untreated. It is characterized by ?

Answer 15

subcutaneous granulomas (gummas). Although neurosyphilis can occur at any time after initial infection, it is more likely to present with tertiary syphilis and manifest with dementia, personality changes, and posterior spinal cord degeneration (tabes dorsalis).
Note that symptoms are generally associated with a single stage but may also overlap.
Syphilis is treated with penicillin G.

Question 16

Herpes simplex, which can disseminate to cause encephalitis, keratitis, and esophagitis, presents with painful, shallow ulcers. Gonorrheal infections, which can cause septic arthritis—characterized by fever with joint pain and synovial inflammation—do not present with penile ulcers or lesions and are usually asymptomatic in men. Likewise, chlamydia is usually an asymptomatic infection but can present with?

Answer 16

purulent urethral discharge and fever or inguinal lymphadenopathy and swelling, depending on the serovar. (D-K serovars cause urethritis; L1-L3 serovars cause lymphogranulosa venereum.)

Question 17

Syphilis is caused by T. pallidum, which can be diagnosed with VDRL titers and FTA-ABS testing. Symptoms of syphilis include an initial painless genital ulcer. Left untreated, this infection can cause ?

Answer 17

subcutaneous granulomas, dementia, and personality changes.

Question 18

This patient, who is sexually active and reports inconsistent use of birth control, presents with amenorrhea for two months; her home pregnancy test yielded a positive result. Her physician has likely ordering a pregnancy test that measures the amount of β human chorionic gonadotropin (β-hCG). Structurally, β-hCG shares the identical α subunit as thyroid-stimulating hormone (TSH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH). LH promotes?

Answer 18

rupture of the ovarian follicle during ovulation.

Given the identical α subunit, the β subunit confers specificity to LH, FSH, TSH, and β-hCG. These hormones (except β-hCG) are secreted from the anterior pituitary gland. β-hCG is secreted by the syncytiotrophoblasts after fertilization.

Question 19

None of the distractors list hormones that contain an α subunit identical to β-hCG. The hormone that promotes the release of cortisol and thyroid-stimulating hormone (TSH) are adrenocorticotropic hormone (ACTH) and thyroid-releasing hormone (TRH), respectively. The hormone that stimulates milk production is?

Answer 19

prolactin, and the hormone that stimulates uterine contractions during labor is oxytocin.

Question 20

β-hCG is a hormone synthesized from the syncytiotrophoblast after fertilization. It is a marker used in pregnancy tests. It is structurally similar to FSH, LH, and TSH. All four hormones share?

Answer 20

the same α subunit; it is their β subunit that confers functional specificity.

Question 21

This patient is experiencing dyschezia (painful defecation), dyspareunia (pain during sexual intercourse), and dysmenorrhea (painful menstruation). As the physician has noted, the physical exam findings of nodularity along the uterosacral ligament, in association with her symptoms, point to a diagnosis of ?

Answer 21

endometriosis. This condition is characterized by the presence of endometrium-like glands and stroma outside the uterus. Endometriosis is most commonly found in the ovaries, followed by the anterior and posterior cul-de-sac (also known as the rectouterine pouch), broad ligaments, uterosacral ligaments, uterus, fallopian tubes, sigmoid colon, appendix, and round ligaments. These sites are highlighted in the illustration. This patient’s difficulty on defecation suggests that the ectopic tissue is present in the posterior cul-de-sac, as this site is closest to the colon.

Question 22

Complications of endometriosis consist of bowel and ureteral obstruction resulting from pelvic adhesions. Ectopic endometrial glandular tissue is influenced by ovarian hormones and undergoes cyclic bleeding. The earliest visible manifestations of endometriosis are whitish peritoneal plaques. Endometriosis can be observed laparoscopically as small subserosal nodules with a brown appearance. Over time the repeated hemorrhaging can produce extensive fibrosis surrounding the endometrial tissue, which can result in?

Answer 22

adhesions to adnexal structures or to bowel and can obliterate the posterior pelvic cul-de-sac (pouch of Douglas).

Question 23

The cervix is not commonly involved in endometriosis and is seen in fewer than 1% of cases. Ectopic tissue in the fallopian tubes would not cause dyschezia, as this is not the closest site to the colon. The ovaries are the most common sites for ectopic tissue in endometriosis, but this patient’s presentation points more towards the posterior cul-de-sac. The uterus is the normal location of the endometrium and is not considered to have?

Answer 23

ectopic endometrial tissue.

Although the ovaries are the most common site of ectopic tissue in endometriosis, ectopic tissue can be found in other sites such as the posterior cul-de-sac, where it may cause dyschezia, along with dysmenorrhea and dyspareunia.

Question 24

The patient presents with anosmia, subfertility, a history of upper respiratory tract infections, and situs inversus (as indicated by the location of her heart sounds). These symptoms point to a diagnosis of Kartagener syndrome.

In Kartagener syndrome, there is a defect in dynein, leading to poor mucus clearance. Dynein arms are ?

Answer 24

heavy chains with coils and stems that attach from a microtubule pair within the axoneme of cilia or flagella toward an adjacent pair. During a power stroke, the motor domain of the dynein arm undergoes a conformational change that causes the microtubule-binding stalk to pivot, resulting in one microtubule sliding relative to another. This produces the bending movement needed for cilia or flagella to beat and propel the cell. In men, the syndrome can lead infertility due to azoospermia, motile spermatozoa but immotile cilia, or immotile spermatozoa. In women, it can cause subfertility due to decreased fallopian tube function, leading to delay in the transit of the ovum from the ovary to the ampulla, the most common site of fertilization. Also, in rare cases, the decreased function of the fallopian tube may lead to ectopic pregnancy. Situs inversus is also associated with this disorder.

Question 25

Collagen α chains in triplets describes the structure of collagen fibrils. A defect in collagen structure results in connective tissue diseases such as scurvy, Ehlers-Danlos syndrome, or osteogenesis imperfecta. Numerous adjoining E-cadherin molecules with actin filaments describes the zona adherens junction. Modifications in the expression and function of adherens junction components can result in pathologic conditions such as cerebral cavernous malformation and alterations of vascular morphology seen in tumors. Multilobular nucleus with?

Answer 25

enzyme-filled granules describes neutrophils. A defect in neutrophils can result in conditions such as chronic granulomatous disease and Chédiak-Higashi syndrome, both of which affect immunity but would not cause infertility. Two longer heavy chains and two shorter light chains linked by disulfide bonds describes antibodies. A defect in antibody structure may affect immunity, but not fertility.

Question 26

Kartagener syndrome, or primary ciliary dyskinesia, is due to a dynein arm defect that results in impaired ciliary function that can lead to subfertility in women and infertility in men, recurrent upper respiratory tract infections, and situs inversus (dextrocardia, more specifically). Dynein arms are?

Answer 26

heavy chains with coils and stems that attach from a microtubule pair within the axoneme of cilia or flagella toward an adjacent pair.

Question 27

This woman, who presents with severe lower abdominal pain, fever, and tachycardia during labor, has been diagnosed with endometritis, an inflammation due to infection of the uterine lining. Endometritis infection is usually polymicrobial and anaerobic. Although endometritis can be associated with sexually transmitted infections, in this case, the condition is the result of prolonged rupture of the membranes. The patient’s acutely increased creatinine level after antibiotic treatment suggests that a nephrotoxic drug was used. The antimicrobial management of endometritis includes?

Answer 27

gentamicin and clindamycin with or without ampicillin.

Gentamicin is an aminoglycoside that is used to treat severe gram-negative rod infections. Toxicities include nephrotoxicity, ototoxicity, and teratogenicity. Aminoglycosides are bactericidal and act by inhibiting the formation of the initiation complex by binding to the 30S ribosomal unit and causing misreading of messenger RNA. Because they require oxygen for uptake, aminoglycosides are ineffective against anaerobes.

Question 28

Vancomycin is associated with nephrotoxicity; however, it is not commonly used in the management of endometritis.
Aztreonam is usually not associated with serious adverse effects, although it can cause rash, phlebitis, and gastrointestinal upset.
Fluconazole is an?

Answer 28

antifungal agent that causes headache, nausea, and abdominal pain.
Tetracycline binds calcium and other metallic ions, causing discoloration of teeth and inhibition of bone growth, as well as photosensitivity.

Question 29

Gentamicin, an aminoglycoside, is known to be potentially nephrotoxic, ototoxic, and teratogenic. In the treatment of endometritis, gentamicin may be used?

Answer 29

in combination with clindamycin with or without ampicillin.

Question 30

This asymptomatic patient with a history of sexual activity at an early age, infrequent use of protection, and multiple partners is found to have high-grade dysplasia on a Pap smear and laboratory findings. The causative agent of cervical dysplasia and cancer is the human papillomavirus (HPV). The black square in the histology image shows a high-grade intraepithelial lesion.

The E6 and E7 HPV gene products downregulate p53 and pRb, respectively, allowing the cell to?

Answer 30

cycle out of control, despite any damage to cellular DNA. Tumor suppressors, such as p53 and hypophosphorylated RB, normally inhibit G1-to-S progression; mutations in these genes result in unrestrained cell division. Cervical intraepithelial neoplasia (CIN) can progress in three stages:
CIN 1 occurs when dysplasia involves lower third of epithelium or less,
CIN 2 occurs when dysplasia involves lower third to lower two-thirds of the epithelium
CIN 3 occurs when dysplasia extends above lower two-thirds of epithelium, if full thickess involvement then can be called carcinoma in situ. If dysplasia is present in the full epithelium, the patient has carcinoma in situ.

Question 31

Blood vessel growth factors are not targeted by the HPV virus and the oncogenes from the HPV virus do not directly activate DNA replication. Oncoproteins such as the HPV gene products are unlikely to inhibit the mitogenic signal transduction, and the HPV virus does not affect?

Answer 31

the activation of the RNA-dependent DNA polymerization.

The human papillomavirus causes cervical dysplasia and and in some cases, cancer by allowing the cell to cycle out of control, despite any damage to cellular DNA.