Repro USMLE step 1 9-5 (8) Flashcards
This patient presents with heavy menstrual bleeding (menorrhagia), bleeding between periods, and an asymmetrically enlarged uterus. The pathology slide shows a monotonous population of spindled cells with blunt-ended, “cigar-shaped” nuclei and abundant eosinophilic cytoplasm. The cells are arranged in intersecting fascicles causing the nuclei to stream like a school of fish—the classic presentation and microscopic description of a fibroid or leiomyoma. Fibroids are common smooth muscle tumors that usually manifest with multiple masses. These tumors are benign and can be associated with?
dysmenorrhea (menstrual pain), menorrhagia, menometorrhagia (frequent menstrual bleeding that is excessive and irregular in amount and duration), infertility, and abnormal findings on pelvic examination including palpable masses extending from the uterus.
Because fibroids are estrogen sensitive, they tend to increase in size during menses or pregnancy and decrease in size after menopause. Treatment of fibroids is dependent on the severity of symptoms and fertility concerns. Hysterectomy is performed for women with severe symptoms who do not wish to preserve fertility. Some women may benefit from uterine fibroid embolization, a fertility-sparing treatment in which embolic agents are introduced to the uterine arteries. The therapeutic goal is to block the fibroid blood vessels, causing the tumors to shrink and die. It is important to note that myomectomy is not used in the treatment of ?
submucosal leiomyomas, since it leads to scarring and subsequent infertility. Medical therapy can be tried with monotherapy or combinations of gonadotropin-releasing hormone analogs (leuprolide), combined oral contraceptives, progestins, and/or gonadotropin-releasing hormone antagonists (cetrorelix).
A mass that enlarges after menopause would be suggestive of uterine or endometrial cancer. Formation of chocolate cysts is associated with endometriosis. Endometriosis usually presents with dyspareunia, dyschezia, and palpable, tender nodularity, which this patient does not have. Malignant transformation of the mass is very rare and would present with areas of necrosis and hemorrhage microscopically. Pelvic inflammatory disease commonly presents with?
odiferous vaginal discharge, pain with sexual intercourse, and urinary symptoms, as well as a history of multiple unprotected sexual encounters.
Multiple masses in a premenopausal woman with dysmenorrhea suggest?
uterine fibroids (also called leiomyomas), which are estrogen-sensitive benign tumors of the smooth muscle. Leiomyomas classically present with an asymmetrically enlarged uterus and tend to enlarge during menses or pregnancy.
This patient presents at age 36 years for her first physical examination since high school, which means she did not have her routine Pap test at age 21 years. Her recent Pap test results, as described in the question stem as severe dysplasia with undifferentiated neoplastic cells that span more than two-thirds of the epithelium, is diagnostic for cervical intraepithelial neoplasia (CIN). CIN is a premalignant transformation of the cells of the cervix, often secondary to exposure to the human papillomavirus (HPV), which may progress to cervical cancer if left untreated.
HPV promotes neoplasia through production of the viral proteins E6 and E7. The E6 protein binds and ubiquinates the p53 (tumor suppressor protein), leading to the degradation of p53 by proteasomes. Decreased presence of p53?
decreases the transcription of p21 protein. The p21 protein is a cyclin-dependent kinase inhibitor that functions as a cell-cycle regulator between the G1-to-S phase of the cell cycle. Therefore, the decreased levels of p21 protein, as a result of the presence of the E6 protein, subsequently cause inappropriate G1–S progression.
In addition, the normal function of the retinoblastoma (Rb) protein is to stop the progression of G1–S phase of the cell cycle. The second viral protein, E7, produced by HPV binds to the Rb protein and prevents it from mediating the G1–S phase inhibition. Thus, loss of both p53 and Rb by HPV viral proteins, E6 and E7, respectively, leads to?
inhibition of cell-cycle regulation and evasion of apoptosis.
Vaccines exist to help protect against HPV infections and the associated cancers. The vaccine is recommended for girls aged 9-26 years and boys aged 9-21 years. Two vaccines exist: a quadrivalent vaccine that immunizes against HPV types 6, 11, 16, and 18 and a 9-valent vaccine that immunizes against HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58. HPV types 16 and 18 are the most common types associated with the development of malignant lesions.
The other answer choices do not address the correct pathogenesis of cervical cancer by HPV viral proteins E6 and E7:
Hyperphosphorylation of Rb is seen in healthy cells, as hypophosphorylation activates Rb and inhibits G1–S progression.
As mentioned previously, E6 increases, not decreases, ubiquitination of Rb.
DNA repair and inhibition of signal transduction are not appreciated in?
the E6 and E7 pathway.
The p21 protein is a cyclin-dependent kinase inhibitor that functions as a cell-cycle regulator between the G1-to-S phase of the cell cycle. Therefore, the decreased levels of p21 protein, as a result of the presence of the E6 protein, subsequently cause inappropriate G1–S progression. Inappropriate progression of the cell cycle can lead to?
the development of malignancy, such as cervical cancer.
The patient is a young boy who presents with delayed developmental milestones, short stature, hypotonia (poor suckling as an infant), obesity, small hands and feet, and hypogonadism. These signs and symptoms are most suggestive of?
Prader-Willi syndrome. The images below illustrate some of the typical facial features (eg, narrow forehead, downward corners of the mouth) associated with this syndrome.
Prader-Willi syndrome has been localized to the 15q12 band. Some genes in the 15q12 region are maternally imprinted (turned off via histone and DNA modifications), whereas some genes in the same region are paternally imprinted. Imprinted genes are epigenetically silenced. In an individual with Prader-Willi syndrome, the genes that would normally only be active on the chromosome inherited from the father (because they are maternally imprinted) have been deleted in the paternal chromosome; thus an individual with Prader-Willi syndrome has no functional copies of these genes.
Deletion of q12 on the maternally derived chromosome 15 causes Angelman syndrome, which presents with severe intellectual and developmental disability, ataxia, inappropriate laughter or smiling, and seizures. Maternal alcohol use during pregnancy leads to distinctive craniofacial abnormalities and intellectual disability. Maternal use of phenytoin during pregnancy leads to fetal hydantoin syndrome, which is associated with growth deficiencies, facial deformities, and hypoplastic nails of the fingers and toes. Trinucleotide CGG repeats lead to?
fragile X syndrome, characterized by intellectual disability, attention deficit/hyperactivity disorder, prominent ears, hyperextensibility of joints, and macroorchidism.
Prader-Willi syndrome (deletion of q12 on paternally derived chromosome 15) is a genetic disease that manifests with?
hypotonia at birth and later with intellectual disability, short stature, and obesity.
This patient, who presents with burning on urination, a history of multiple sexual partners, and positive leukocyte esterase and nitrite tests (the former indicating leukocyte activity, the latter indicating the presence of gram-negative bacteria) most likely has a urinary tract infection (UTI). Though the offending organism cannot be identified with the information provided, it is likely that the patient’s UTI is caused by Escherichia coli, a gram-negative rod that is commonly implicated in this condition.
Ciprofloxacin, which the patient’s physician chose for empirical treatment of the patient’s UTI, is a fluoroquinolone antibiotic that acts by inhibiting DNA gyrase, which counteracts the supercoiling of DNA during replication or transcription. It is bactericidal and is used to treat aerobic gram-negative rod infections, especially UTIs, sexually transmitted disease, and mycobacterial infection. Common adverse effects include?
gastrointestinal upset (eg, diarrhea), skin rashes, headache, and dizziness.
Tendinitis and/or tendon rupture as well as other connective tissue injury may rarely occur, which is why the FDA now recommends that at the first sign of tendon pain, swelling, or inflammation, patients should stop taking the fluoroquinolone, avoid exercise, and promptly contact their physician for tendon evaluation. In children, leg cramps, myalgia and arthropathy with erosions of connective tissue can occur. For this reason, systemic fluoroquinolones are not recommended for routine use in children younger than 18 years of age. Finally, on rare occasion, fluoroquinolones can cause QT prolongation.
Fluoroquinolones act by inhibiting DNA gyrase. Significant adverse effects of this class of antibiotics include gastrointestinal disturbances, such as?
diarrhea; rash; tendinitis; and myalgia (in children). GI symptoms are the most common adverse effect associated with fluoroquinolones.
Myalgia, arrhythmia, and tendinitis are associated with fluoroquinolone use, but these adverse effects are very rare (<1% of patients for each of these AEs). Ototoxicity is associated with?
aminoglycosides and vancomycin, not with fluoroquinolones.
This patient’s absence of erections during periods of rapid eye movement (REM) and morning tumescence, indicates that his symptoms are pathologic, not psychological, and that he requires pharmacologic treatment for erectile dysfunction. Sildenafil is a first-line treatment for this condition. The drug acts by inhibiting cGMP phosphodiesterase, which increases?
cGMP levels via direct release of nitric oxide (NO), thus leading to smooth muscle relaxation in the corpus cavernosum. Smooth muscle relaxation allows increased blood flow to the corpus vascularity.
Some of sildenafil’s adverse effects include headache, flushing, and disturbances in color vision. Sildenafil is contraindicated in patients taking nitroglycerin or other nitrates because it enhances their effect.
