Male Repro- 2 Flashcards
A 16-year-old boy is brought to the emergency department due to severe right groin pain that has worsened over the past 12 hours. During the last month, the patient has had several episodes of mild scrotal pain while walking between classes at school. He has no history of traumatic injury and is sexually active. Medical history is unremarkable except for an inguinal hernia repaired a year ago. Temperature is 36.9 C (98.4 F), blood pressure is 116/78 mm Hg, and pulse is 86/min. On examination, the right hemiscrotum is swollen and tender. The bisected gross specimen from an orchiectomy is shown in the image below.
Which of the following is the most likely mechanism of this patient’s acute testicular pain?
A. Abnormal collection of fluid within the scrotum
B. Anatomic defect causing increased mobility of the testis
C. Clonal proliferation of testicular germ cells
D. Migration of bacteria from the urinary tract
E. Postsurgical clotting of the pampiniform plexus
Answer B
This patient with severe groin pain and unilateral scrotal swelling has evidence of hemorrhagic infarction (ie, venous congestion with extravasation of blood) of the testicle, consistent with testicular torsion.
Testicular torsion is caused by spermatic cord twisting, which most commonly occurs in patients with inadequate fixation of the lower pole of the testis to the tunica vaginalis. This anatomic defect (ie, bell clapper deformity) allows for increased mobility of the testis, which can turn freely within the scrotum. As the testis and cord rotate, the pampiniform plexus becomes compressed, leading to reduced venous outflow and hemorrhagic infarction of the testicle. Diminished testicular perfusion can rapidly progress to ischemia and necrosis.
The classic presentation is an acute onset of severe scrotal pain and swelling with an elevated, high-riding testis and an absent cremasteric reflex. Groin or lower abdominal pain may be the initial presentation in some, and there may be a history of milder, self-resolving episodes caused by intermittent torsion, as seen in this patient. Emergency surgical detorsion (ideally within 4-6 hr of symptom onset) is required to salvage the testis, but orchiectomy may be necessary if the testicle is necrotic or blood flow cannot be restored.
(Choice A) An abnormal fluid collection between the parietal and viscera tunica vaginalis describes a hydrocele, which causes scrotal swelling but not acute pain.
(Choice C) Clonal proliferation of testicular germ cells is seen with a germ cell tumor (eg, seminoma), which most often presents as a nontender testicular mass.
(Choice D) Infection (eg, epididymitis, epididymoorchitis) due to bacterial migration from the urinary tract can cause scrotal pain and swelling, but additional symptoms (eg, fever, dysuria) are often present, and a history of sporadic painful episodes is not typical. Moreover, testicular edema occurs due to inflammation, not hemorrhagic infarction.
(Choice E) Postoperative clotting of the pampiniform plexus (ie, thrombotic varicocele) is a rare surgical complication that causes acute scrotal pain and swelling. However, this patient’s inguinal hernia repair was a year ago, making postsurgical complication unlikely.
Educational objective:
Testicular torsion is characterized by spermatic cord twisting due to an anatomic defect that allows increased testicular mobility. The presentation includes severe scrotal pain and swelling due to venous compression and hemorrhagic infarction of the testis.
Answer D
Prostate cancer is an androgen-dependent tumor early in the disease course. Because androgens in men are primarily made in the testes, patients with recurrent (eg, rising prostate-specific antigen level after prostatectomy) or disseminated (eg, regional lymphadenopathy) prostate cancer are generally treated with surgical or medical orchiectomy to reduce systemic androgen levels, thereby reducing the primary growth factor for the tumor.
Androgen production in men is controlled by the hypothalamic-pituitary-testicular axis. GnRH is secreted by the hypothalamus in a pulsatile fashion, which stimulates pituitary gonadotrophs to release luteinizing hormone (LH); LH then stimulates the Leydig cells of the testes to generate and secrete androgens. Patients who undergo medical orchiectomy are often treated with a GnRH analogue (eg, buserelin), which stimulates the pituitary gland in a continuous fashion, leading to a down-regulation of the GnRH receptor. This subsequently drops LH secretion, which lowers androgen production by the testes.
However, because GnRH analogues temporarily activate the GnRH receptor prior to downregulation, patients often develop a surge in androgens during the first few weeks of therapy. Therefore, androgen-receptor inhibitors (eg, bicalutamide) are usually concurrently administered during the first weeks of GnRH analogue therapy to block the activity of androgens on the tumor cells.
(Choice A) Although adrenal synthesis of androgens is not an initial target in prostate cancer, patients who have progressive disease despite medical or surgical orchiectomy are often treated with abiraterone, which limits androgen production in the tumor, adrenal gland, and testes by inhibiting the enzyme 17alpha-hydroxylase.
(Choice B) Chemotherapy is often administered with GnRH analogues in patients with metastatic prostate cancer to induce cancer cell death. However, bicalutamide is an androgen-receptor inhibitor, not a chemotherapy agent.
(Choice C) Sexual dysfunction occurs in the majority of men given GnRH analogues due to reduced libido and erectile dysfunction. This can be managed with phosphodiesterase inhibitors.
(Choice E) GnRH analogues often cause vasomotor symptoms (hot flashes) due to estrogen withdrawal. Treatment is similar to menopausal hot flashes in women; progesterone, cyproterone, and selective serotonin reuptake inhibitors are somewhat effective.
Educational objective:
Because prostate cancer is an androgen-dependent tumor, patients with advanced disease are generally treated with surgical or medical orchiectomy. Medical orchiectomy uses GnRH analogues to reduce LH production, which subsequently reduces androgen production in the testes. Because there is an initial surge in androgens at the start of therapy (due to stimulation of the GnRH receptor), patients prescribed GnRH therapy are usually treated with a few weeks of androgen-receptor inhibitors (eg, bicalutamide).
Answer B
The prostatic plexus lies within the fascia of the prostate and originates from the inferior hypogastric plexus (which itself is a continuation of the hypogastric nerve with additional input from the pelvic and sacral splanchnic nerves). The lesser and greater cavernous nerves arise from the prostatic plexus and pass beneath the pubic arch to innervate the corpora cavernosa of the penis and urethra. The cavernous nerves carry post-ganglionic parasympathetic fibers that facilitate penile erection. Prostatectomy or injury to the prostatic plexus can cause erectile dysfunction; as a result, surgeons attempt to preserve the integrity of the prostatic fascial shell during surgery.
(Choice A) Detrusor muscle overactivity leads to urge incontinence, which is more common in women. The detrusor muscle is controlled by parasympathetic fibers from the pelvic splanchnic nerves and inferior hypogastric plexus, which are not usually injured during prostatectomy.
(Choices C, D, and F) Branches of the pudendal nerve innervate the external urethral and anal sphincters. They also provide sensory innervation of the external genitalia. Pudendal nerve injury can lead to fecal incontinence, decreased penile sensation, or external urethral sphincter paralysis. Although urethral muscle injury can occur during prostate surgery, injury to the main pudendal nerve is less common with prostatectomy.
(Choice E) The cremasteric reflex is elicited by lightly stroking the medial thigh, which causes contraction of the cremaster muscle to pull up the ipsilateral testis. This reflex is mediated by the genitofemoral nerve, which originates from the L1-L2 spinal nerves. Loss of the cremasteric reflex is most commonly seen with testicular torsion or L1-L2 spinal injury.
Educational objective:
The prostatic plexus (inferior hypogastric nerves plus pelvic and sacral splanchnic nerves) lies within the fascia of the prostate and innervates the corpus cavernosa of the penis, which facilitates penile erection. As a result, prostatectomy or injury to the prostatic plexus can cause erectile dysfunction.
Answer A
This patient’s obstructive urinary symptoms and mildly enlarged prostate are consistent with benign prostatic hyperplasia (BPH). In addition, he has hypertension that has not been well controlled. When possible, it is desirable to choose drugs that can address multiple issues to minimize adverse effects and drug interactions.
In this patient, an alpha-1 blocker (eg, doxazosin, prazosin, terazosin) can be used to treat both the BPH symptoms and the hypertension. Although alpha-1 blockers are not first-line medications for hypertension, they can be useful second-line drugs in hypertensive patients with concomitant BPH.
Alpha-1 blockers work by relaxing smooth muscle in the bladder neck and prostate, opening up the bladder outlet and decreasing the resistance to the flow of urine. They also relax smooth muscle tone in arterial walls, thus decreasing blood pressure. Uroselective alpha-1 blockers (specific for alpha-1A subtype), such as alfuzosin, silodosin, and tamsulosin, affect only the urinary tract smooth muscles; therefore, they would not be helpful in decreasing blood pressure (Choice F).
(Choice B) Finasteride is a 5-alpha-reductase inhibitor that is effective for the treatment of BPH but has no effect on blood pressure. It works by inhibiting the conversion of testosterone to dihydrotestosterone, the hormone that causes progressive glandular enlargement in BPH. After being administered for several months, finasteride decreases the size of the prostate.
(Choice C) Hydralazine is a powerful, typically third-line antihypertensive that works by relaxing smooth muscles in the arterial walls. It would not be useful in the treatment of BPH.
(Choice D) Hydrochlorothiazide is a thiazide diuretic that functions at the distal convoluted tubule of the nephron to prevent the reabsorption of sodium, chloride and water by blocking a Na/Cl co-transporter. It is one of the first-line medications for the treatment of primary hypertension. Diuretics have no role in the treatment of BPH.
(Choice E) Metoprolol is a selective beta-1-receptor blocker used to treat hypertension and coronary artery disease. It works by blocking adrenergic stimulation of the heart, causing the heart to contract less forcefully and less frequently. Beta-1-receptor blockers would not help with BPH symptoms.
Educational objective:
Alpha-1 blockers such as doxazosin, prazosin, and terazosin are useful for the treatment of both benign prostatic hyperplasia and hypertension. To minimize adverse effects and drug interactions, it is desirable to prescribe a medication that can address multiple issues at once.
Answer A
The corpora cavernosa of the penis receive sympathetic innervation (T11-L2) via the superior hypogastric plexus and cavernosal nerves.
In the flaccid state, tonic alpha-adrenergic (norepinephrine) sympathetic activity maintains high vascular and trabecular smooth muscle tone, preventing the corpora from engorging with blood.
In an erection, activation of parasympathetic nerve fibers (S2-S4) induces relaxation of smooth muscle in cavernous arteries and trabeculae. The increased blood flow fills the relaxed corpora, which subsequently causes compression of the emissary veins against the tunica albuginea, blocking the outflow of blood and further increasing pressure within the corpora cavernosa.
This patient has priapism, a painful, firm erection in the absence of sexual stimulus or beyond the normal duration of sexual activity. Priapism is usually idiopathic but can be caused by medications or drugs (eg, trazodone, cocaine) or disease states (eg, sickle cell disease) that disrupt the normal outflow of blood from the corpora cavernosa. Treatment usually includes penile injection of an alpha-adrenergic agonist (eg, phenylephrine), which induces contraction of cavernous smooth muscle; this reduces venous obstruction by the engorged corpora, increasing venous outflow and promoting detumescence.
(Choice B) Alpha-1 antagonists (eg, tamsulosin, doxazosin) inhibit tonic sympathetic activity and can trigger priapism.
(Choice C) Beta-1 agonists (eg, dobutamine) are positive inotropic agents that increase stroke volume and cardiac output. This will increase blood flow to the penis and worsen priapism.
(Choice D) Beta-2 agonists induce trabecular smooth muscle relaxation and increase blood flow to the penis, potentially worsening priapism.
Educational objective:
The penile flaccid state is maintained by tonic alpha-adrenergic (norepinephrine) sympathetic activity, causing high vascular and trabecular smooth muscle tone, preventing corporal engorgement with blood. Priapism can be treated with penile injections of an alpha-adrenergic agonist (eg, phenylephrine), which induce smooth muscle contraction, leading to detumescence.
Answer E
The vas deferens (ductus deferens) is a long muscular duct that runs from the epididymis, via the spermatic cord, to the ejaculatory duct. In addition to transporting sperm, it functions as a reservoir to store and protect sperm following spermatogenesis.
Vasectomy is a male sterilization procedure that involves transection of the vas deferens bilaterally to block the transport of new sperm. However, vasectomy has no effect on existing sperm distal to the transection; a patient can still have viable sperm in the distal vas for up to 3 months and at least 20 ejaculations following vasectomy. Sexual intercourse can typically be resumed within a week following the procedure, but pregnancy is still possible due to residual sperm in the ejaculate. Therefore, another method of birth control must be used after vasectomy until semen analysis confirms azoospermia.
(Choice A) Interest in sexual activity is generally unchanged following vasectomy. Some patients report increased interest due to the reduced possibility of unplanned pregnancy; decreased interest is only occasionally reported.
(Choice B) Vasectomy transects the vas deferens where it runs within the spermatic cord in the scrotum. Arterial and neuronal supplies to the erectile corpora are not at risk, and erectile impairment is not a common complication.
(Choice C) Semen is composed primarily of fluid secreted from the seminal vesicles and prostate; spermatozoa make up only 2%-5% of semen by volume. Therefore, vasectomy has little effect on the volume of ejaculate.
(Choice D) The endocrine function of the testes is unaffected by vasectomy, and testicular Leydig cells continue to produce testosterone at prevasectomy levels.
Educational objective:
Following vasectomy, viable sperm remain in the portion of the vas deferens distal to the transection. Patients can still have viable sperm in the ejaculate for up to 3 months and at least 20 ejaculations after the procedure.
Answer D
Breast enlargement in adolescent boys, or gynecomastia, is often physiologic during puberty. However, a pathologic cause should be suspected when the onset is outside of midpuberty (eg, Tanner 1 or 5), the tissue is rapidly enlarging, or other abnormalities on physical examination suggest a systemic disorder. In this case, the patient is age 17 but has small/firm testes, a sign of hypogonadism. His learning disability and tall height make Klinefelter syndrome, the most common cause of primary hypogonadism, the most likely diagnosis.
Patients with Klinefelter syndrome (47,XXY karyotype) typically have atrophied, hyalinized seminiferous tubules, resulting in low inhibin levels, and damaged Leydig cells, resulting in low testosterone levels. The lack of feedback inhibition results in excess gonadotropin production (ie, increased FSH and LH). Elevated FSH upregulates aromatase, the enzyme that converts androgens into estrogens, and therefore causes increased estradiol levels (Choice A). The increase in the estrogen/testosterone ratio is responsible for breast tissue growth.
Other phenotypic findings in patients with Klinefelter syndrome include tall stature and absent secondary sex characteristics (eg, deep voice, facial/pubic hair). Cognitive impairment is typical and characterized by learning disabilities and impaired social skills.
(Choice B) Increased androstenedione levels due to anabolic steroid use can cause irreversible gynecomastia and testicular atrophy. However, exogenous steroids would also cause acne, male pattern baldness, and aggressive behavior, none of which are seen in this patient. In addition, hastened epiphyseal closure (ie, reduced height potential) is characteristic with adolescent steroid use.
(Choice C) Testicular germ cell tumors produce excessive β-hCG, which can result in gynecomastia. However, a rapidly growing testicular mass, not small, firm testes, would be present on examination.
(Choice E) Hyperprolactinemia due to a prolactinoma can result in gynecomastia; high prolactin suppresses GnRH, which leads to reduced LH and testosterone secretion. However, this diagnosis is uncommon and often delayed in male patients, usually resulting in associated neurologic findings (eg, headache, vision changes) due to local tumor growth. In addition, hyperprolactinemia is not associated with learning disabilities or tall stature.
Educational objective:
Pathologic gynecomastia should be suspected in patients who also have signs of hypogonadism (eg, small/firm testes, absent pubic hair). Klinefelter syndrome (47,XXY) is the most common cause of primary hypogonadism, and patients have low testosterone, elevated gonadotropin (FSH, LH), and relatively increased estradiol levels.
Answer A
The gonadal arteries arise from the abdominal aorta slightly below the renal arteries. Each gonadal artery courses obliquely downward and laterally within the retroperitoneal space near the psoas major muscle. After crossing anteriorly over the ureter, the gonadal arteries run parallel to the external iliac vessels and eventually traverse the inguinal canal to supply the testes via the spermatic cord in males.
This patient most likely has testicular torsion, which is usually due to inadequate fixation of the lower pole of the testis to the tunica vaginalis. Testicular torsion is caused by twisting of the spermatic cord, resulting in compression of the pampiniform plexus of the testicular vein and reduced venous outflow. Arterial blood flow in the testicular arteries is initially preserved or slightly decreased, leading to engorgement and eventual hemorrhagic infarction. Torsion is characterized by acute, severe pain with nausea/vomiting, an asymmetrically high-riding testis, and absent cremasteric reflex (elevation of testis while pinching the skin in upper thigh).
(Choices B and C) The external and internal iliac arteries arise from the common iliac artery. The external iliac artery travels underneath the inguinal ligament and becomes the femoral artery, which supplies the lower extremity. The internal iliac artery provides blood supply to the pelvic wall/viscera, buttock, female reproductive organs, bladder, and medial thigh.
(Choice D) The internal pudendal artery is a branch of the internal iliac artery and provides blood supply to the anal canal, scrotum, and penis. However, it does not provide blood supply to the testis.
(Choice E) The obturator artery arises from the internal iliac artery and provides blood supply to the pelvis, bladder, and parts of the femoral head and medial thigh muscles.
(Choice F) The renal artery provides blood supply to the kidney. Branches of the renal artery supply the ureter but do not travel to the testis. Unlike the gonadal arteries, the gonadal veins arise from different structures. The right gonadal vein drains directly into the inferior vena cava while the left gonadal vein drains into the left renal vein.
Educational objective:
Testicular torsion is due to twisting of the testis around the spermatic cord (containing the gonadal artery), which can eventually lead to ischemia. The gonadal arteries arise from the abdominal aorta. The right gonadal vein drains directly into the inferior vena cava while the left gonadal vein drains into the left renal vein.
Answer C
Sertoli and Leydig cells are the hormone-producing cells of the testis. Leydig cells, which are analogous to female theca cells, produce testosterone in response to stimulation by luteinizing hormone. LH is released from the anterior pituitary in response to gonadotropin-releasing hormone (GnRH) from the hypothalamus. Testosterone causes feedback inhibition of both LH and GnRH release.
Sertoli cells, which are analogous to female granulosa cells, produce the hormone inhibin in response to FSH from the anterior pituitary. Inhibin suppresses FSH production by the anterior pituitary, although it does not feed back on the hypothalamus. Sertoli cells also facilitate spermatogenesis within the seminiferous tubules.
Steroidogenic factor-1 (SF-1) is a nuclear receptor that regulates the transcription of several genes involved in steroidogenesis, sexual development, and reproduction. Mutations of SF-1/NR5A1 cause a wide variety of phenotypic features in males and females, including genital malformations and Sertoli cell failure. Selective impairment in Sertoli cell function would cause decreased production of inhibin and lead to increased FSH levels (Choice D), as well as infertility due to impaired sperm production. However, the Leydig cells are unaffected, so no changes in testosterone or LH levels would be expected.
(Choice A) Decreased release of all of these hormones is a sign of anterior pituitary failure, which can occur with Kallmann syndrome, sellar mass lesions, pituitary apoplexy, or radiation injury.
(Choice B) This pattern would be observed if the Leydig cells were selectively impaired. Isolated Leydig cell failure has been reported in patients with LH/hCG receptor defects on Leydig cells.
(Choice E) Most pituitary adenomas arising from gonadotrophs produce only the biologically inactive alpha subunit (nonfunctioning adenomas), although adenomas producing intact FSH are occasionally seen. Inhibin levels may be either normal or elevated. Males with FSH-secreting adenomas are usually asymptomatic, but some will have enlargement of the testes.
Educational objective:
Sertoli cells produce inhibin in response to FSH from the anterior pituitary. Inhibin suppresses FSH production in the pituitary. Sertoli cells also facilitate spermatogenesis within the seminiferous tubules. Impaired Sertoli cell function would lead to decreased production of inhibin, increased FSH levels, and impaired fertility.
Answer A
Prostate cancer is typically diagnosed by transrectal ultrasound–guided biopsy, which uses ultrasound guidance to take multiple core biopsy samples from random locations within the peripheral zone of the prostate. Subsequent histopathologic examination confirms the presence of cancer and determines the degree of glandular architecture abnormality, which is summarized by the Gleason grade.
The lowest Gleason grade of 1 is assigned to well-differentiated tumors; these tumors resemble normal prostatic tissue and are generally arranged into small, well-formed, closely packed glands. In contrast, the highest Gleason grade of 5 is assigned to poorly differentiated tumors; these tumors do not resemble normal prostatic tissue and are generally arranged into sheets of invasive cells with no glandular elements. The 2 predominant Gleason grades in the core biopsies are added together to generate the Gleason score (eg, a tumor that is mostly Gleason grade 3 and 4 would have a Gleason score of 7). The higher the Gleason score, the higher the risk of spread outside of the prostate.
Staging is a marker of degree of spread from the site of cancer origin. Low stage is seen in those with disease confined to the prostate; a higher stage is seen in those with regional (eg, lymph node) or metastatic (eg, bone) lesions. In this case, the presence of enlarged iliac nodes likely indicates metastases to the regional lymph nodes; therefore, he would have a higher stage of disease.
Educational objective:
Prostate cancer is graded by Gleason grade, which is a measure of glandular architecture disruption and risk of extra-organ spread; poorly differentiated prostate cancer (eg, no glandular structure) is assigned a high Gleason grade, whereas well-differentiated prostate cancer (eg, well-formed glandular structure) is assigned a low Gleason grade. Staging is a marker of the extent of spread from the primary cancer site; regional lymph node involvement or distant metastases indicate a higher stage of disease.
Answer C
The human glycoprotein hormone family includes 4 hormones: hCG, TSH, FSH, and LH. Each is a heterodimeric structure consisting of an identical alpha subunit noncovalently associated with a unique but homologous beta subunit, which confers its specific biologic properties. The beta subunits of hCG and TSH share significant sequence homology; this structural similarity allows hCG to bind and activate the TSH receptor, albeit with much lower affinity than TSH.
hCG is normally produced in the placenta but can also be released by a number of malignancies, especially choriocarcinoma and nonseminomatous germ cell tumors. This patient likely has a testicular germ cell tumor producing large quantities of hCG. Activation of TSH receptors on the thyroid gland by high levels of hCG can cause paraneoplastic hyperthyroidism, presenting with weight loss, sweating, and heat intolerance.
(Choice A) Alpha-fetoprotein can be used as a tumor marker for a number of malignancies, including hepatocellular carcinoma and nonseminomatous germ cell tumors of the testes. However, elevated levels would not result in symptoms of hyperthyroidism.
(Choice B) FSH is produced by gonadotrophs in the anterior pituitary cells. It is not a marker for testicular tumors and has no affinity for thyroid receptors.
(Choice D) Lactate dehydrogenase is an enzyme involved in anaerobic glycolysis. Although increased levels can occur with both seminomatous and nonseminomatous tumors of the testes, this enzyme does not interact with TSH receptors.
(Choice E) The majority of circulating alkaline phosphatase comes from bone, liver, gastrointestinal tract, and placenta. Placenta-like alkaline phosphatase is a nonspecific tumor marker that can be increased in testicular seminoma and other malignancies but has no homology with TSH.
Educational objective:
Human chorionic gonadotropin (hCG) has a structure similar to TSH. Patients with testicular germ cell tumors or gestational trophoblastic disease may develop very high serum hCG concentrations, which can stimulate TSH receptors and cause paraneoplastic hyperthyroidism.
Answer B
Testicles develop in the fetal abdomen during organogenesis. Between 8 weeks and full term, each testis descends from the abdomen into the inguinal canal through the deep inguinal ring, which is an opening in the transversalis fascia bounded laterally by the transversus abdominis muscle and medially by the inferior epigastric vessels. Each testis then passes anteromedially through the canal and enters the scrotum via the superficial inguinal ring, which is a physiologic opening in the external oblique muscle aponeurosis above the pubic tubercle.
Cryptorchidism is the failure of one or both testes to descend to the scrotum before birth, which occurs more commonly in preterm neonates. It is associated with a significantly increased risk of testicular cancer and infertility. A testis that is palpable in the inguinal canal typically descends spontaneously by age 6 months. Testes that have not descended by this point are unlikely to do so and require surgical intervention (ie, orchiopexy).
In this case, the patient’s undescended testicle is lodged within the inguinal canal and must be mobilized through the superficial inguinal ring and stitched into place in the scrotum.
(Choice A) The conjoint tendon is the common tendon of the transversus abdominis and internal oblique muscles. It forms part of the posterior wall of the inguinal canal.
(Choice C) The femoral ring is a physiologic opening between the abdominal cavity and the femoral canal. It transmits lymphatic vessels but not the spermatic cord.
(Choice D) The internal oblique muscle aponeurosis contributes to the formation of the conjoint tendon and rectus muscle sheath. In addition, the cremaster muscle originates from the internal oblique muscle itself.
(Choice E) The rectus muscle sheath is formed by the confluence of the aponeuroses of the external and internal oblique muscles and the transversus abdominis muscle.
Educational objective:
The superficial and deep inguinal rings are physiologic openings in the external abdominal oblique aponeurosis and the transversalis fascia, respectively. Surgical repair of an undescended testicle lodged in the inguinal canal involves moving the testis through the superficial inguinal ring and fixing it in the scrotum (ie, orchiopexy).
Answer B
This patient’s vertebral body bony lesions raise strong suspicion for osteoblastic metastases due to prostate adenocarcinoma; his massive pulmonary embolism was likely precipitated by an underlying hypercoagulable state of malignancy. Prostate cancer is the most common non-skin cancer in men, and risk is strongly linked to advancing age. Because most cases develop in the periphery of the prostate gland, urinary symptoms are uncommon until late in the disease course; therefore, the diagnosis is usually prompted by elevated prostate-specific antigen level, abnormal digital rectal examination, or symptoms related to advanced disease (eg, bone pain).
Prostate cancer preferentially metastasizes to bone due to specific adhesion molecules (eg, CXCR4) and receptor ligands (eg, RANK) on the cancer cell surface that adhere to pericytes and bone marrow stromal cells. After it establishes a nidus, the tumor secretes osteoblast differentiation factors (eg, endothelin 1, insulin-like growth factors, platelet-derived growth factors, bone morphogenic proteins) that promote new bone growth. Biopsy of a bone lesion would most likely show disordered trabecular growth and evidence of prostate cancer cells such as irregular glands with enlarged nuclei and prominent nucleoli.
(Choices A, C, D, and E) Osteolytic bone metastases appear on radiology and gross pathology as moth-eaten bone, not areas of bony growth. These bone lesions are typically seen with metastatic melanoma (pleomorphic cells with coarse, brown melanin pigment), multiple myeloma (effacement of marrow with plasmablasts and plasma cells), renal cell carcinoma (sheets of neoplastic cells with abundant clear cytoplasm), and thyroid papillary carcinoma (complex papillary pattern and psammoma bodies).
Educational objective:
Prostate cancer is common in older men and metastasizes primarily to bone due to bone-specific tumor adhesion molecules and receptor ligands on the cellular surface. Prostate cancer causes osteoblastic lesions that result in new bone growth. Biopsy would show disordered trabeculae and signs of prostate cancer such as irregular glands with enlarged nuclei and prominent nucleoli.
Answer D
The presence of a painless, solid testicular mass should always be considered testicular cancer until proven otherwise. Most cases present with a nodule or solid swelling in one testicle, which is often initially noticed by a partner or after a minor trauma. Bimanual examination of scrotal contents generally reveals a firm, hard, or fixed nodule within the tunica albuginea (fibrous covering of testes) that is ovoid in shape and painless to palpation. Because light does not penetrate solid tumors, testicular cancer does not transilluminate (unlike fluid-filled hydroceles) (Choice B). Bilateral scrotal ultrasound and serum tumor markers (eg, alpha-fetoprotein, beta human chorionic growth hormone) are usually obtained next to aid diagnosis.
Most testicular tumors arise in young men (age 15-35) and are derived from a pluripotent testicular germ cell; these testicular germ cell tumors are generally curable with surgery and (when needed) chemotherapy.
(Choice A) Epididymitis is common in young, sexually active men and is usually due to a sexually transmitted infection (eg, Chlamydia trachomatis, Neisseria gonorrhoeae). However, most cases are quite painful, and careful examination usually shows swelling adjacent to, rather than within, the testis.
(Choice C) Syphilitic gummas are a manifestation of tertiary syphilis that can develop many years after initial infection in untreated patients. They generally present with painless, white-gray lesions on the skin that may ulcerate; testicular gummas (syphilitic orchitis) are rare and usually associated with pain and fever.
(Choice E) Testicular hematoma usually occurs after scrotal trauma and generally presents with significant testicular pain and tenderness to palpation.
(Choice F) Varicoceles are due to venous dilation in the pampiniform plexus. They can present with painless testicular swelling but characteristically feel like a “bag of worms” on physical examination. Most decompress with recumbency and grow in size with standing.
Educational objective:
A painless, solid scrotal mass should be considered testicular cancer until proven otherwise. Examination generally reveals a solid, firm, or fixed nodule in the tunica albuginea that is ovoid in shape and painless to palpation. Testicular tumors do not transilluminate.
Answer G
Trazodone is a sedating antidepressant used off-label most often as a hypnotic to treat insomnia associated with depression or antidepressant treatment. It has been associated with the rare but serious side effect of priapism (ie, persistent erection of the penis for >4 hours that is not associated with sexual excitement). Priapism is a medical emergency that, if left untreated, can result in permanent damage to penile tissue and erectile dysfunction. Priapism occurs most often in young adult men.
Trazodone is a serotonin modulator (it antagonizes postsynaptic serotonin receptors and inhibits serotonin reuptake) that has minimal effects on norepinephrine and dopamine. Additional properties include alpha-adrenergic blockade—which may account for the side effects of orthostatic hypotension and priapism—and histamine H1 receptor antagonism, which contributes to its sedating effect. Trazodone should be used with caution in patients with conditions that predispose to priapism (eg, sickle cell disease).
(Choices A, B, and E) These antidepressants have not been associated with priapism. Bupropion is a dopamine-norepinephrine reuptake inhibitor that is not associated with sexual side effects and may reduce sexual side effects induced by selective serotonin reuptake inhibitors (SSRIs) when used as an adjunctive treatment. Citalopram and paroxetine, in contrast, are SSRIs that have been associated with high rates of sexual side effects (eg, decreased libido, anorgasmia, delayed ejaculation).
(Choices C, D, and F) Clomipramine and imipramine are tricyclic antidepressants used as second-line therapy due to their higher side effect burden and risk for cardiotoxicity in overdose. Phenelzine is a monoamine oxidase inhibitor used in the treatment of resistant depression; it requires dietary restrictions due to the risk of hypertensive crisis. These agents do not typically cause priapism.
(Choice H) Zolpidem is a nonbenzodiazepine hypnotic used in the treatment of insomnia; it does not carry a risk of priapism.
Educational objective:
Trazodone is a highly sedating antidepressant commonly used to treat insomnia. Priapism is a rare but serious adverse effect.
Answer D
This patient’s acute testicular pain, posterior testicle tenderness, and pyuria raises suspicion for acute epididymitis. Most cases occur when genitourinary pathogens travel in a retrograde fashion from the urethra via the ejaculatory duct to the vas deferens. The most likely underlying organism can often be inferred based upon the age of the patient:
Young men (age <35) usually develop acute epididymitis due to Chlamydia trachomatis or Neisseria gonorrhoeae, sexually transmitted pathogens acquired during unprotected sexual intercourse. Although these organisms often cause asymptomatic urethritis (no dysuria), pyuria is typically seen on urinalysis. Nucleic acid amplification testing is required for diagnosis because urine culture is generally negative.
Older men (age >35) are less likely to have sexually transmitted infections due to fewer sexual partners and increased rates of monogamy. Acute epididymitis in these patients is generally due to gram-negative colonic flora (eg, Escherichia coli), which contaminate the urethra, ascend into the urinary system, and subsequently invade the ejaculatory duct and vas deferens. Most cases arise in the setting of urethral obstruction (eg, benign prostatic hypertrophy) and are characterized by urinary tract symptoms (eg, dysuria, urinary frequency), bacteruria on urinalysis, and positive urine culture (Choice E).
(Choice A) Mumps can occur in those who did not receive appropriate childhood vaccinations and usually presents with a nonspecific prodrome (fever, malaise, myalgias) followed by parotitis. Complications include orchitis, with high fever and severe diffuse testicular pain, which are not seen in this patient.
(Choice B) Varicocele is characterized by distension of the pampiniform plexus due to elevated gonadal venous pressure. It presents as a soft scrotal mass that feels like a “bag of worms” on palpation. Pain is mild or absent.
(Choice C) Testicular torsion is the result of inadequate fixation of the lower pole of the testis to the tunica vaginalis. It is usually characterized by sudden-onset, severe, unilateral testicular pain; nausea; a high-riding testis; and loss of the cremasteric reflex (elevation of testis on pinching of the skin at the upper thigh).
Educational objective:
Epididymitis presents with acute testicular pain, tenderness, and pyuria. It is caused by retrograde passage of organisms from the urethra into the ejaculatory duct and vas deferens. The microbiology is largely influenced by patient age: epididymitis in young men is usually due to sexually acquired infections (eg, Chlamydia trachomatis, Neisseria gonorrhoeae), whereas in older men (age >35) it is usually due to gram-negative colonic flora.
Answer F
The finding of impaired sperm motility raises concern for primary ciliary dyskinesia (PCD), an autosomal recessive condition caused by a variety of mutations in genes responsible for normal flagellar and ciliary function. The clinical manifestations of PCD include:
Predisposition to upper and lower respiratory tract infections due to impaired mucociliary clearance. Patients develop chronic cough, chronic sinusitis, recurrent otitis media, and bronchiectasis (permanent abnormal airway enlargement).
Randomization of left-right body asymmetry; half of all patients have situs inversus (reversed right/left positioning of internal organs)
Infertility due to impaired function of sperm flagella (men) and immobility of fallopian tube cilia (women).
Patients with the triad of situs inversus, chronic sinusitis, and bronchiectasis are said to have Kartagener syndrome.
(Choice A) A cleft lip results from failure of the maxillary and medial nasal processes to fuse during development. It is not associated with defects in ciliary structure or function.
(Choice B) Coarctation of the aorta may be seen in Turner (XO) syndrome.
(Choice C) Fat malabsorption can occur in cystic fibrosis due to pancreatic insufficiency. Although male patients with cystic fibrosis are typically infertile, this results from bilateral absence of the vas deferens (azoospermia) as opposed to the impaired sperm motility seen in Kartagener syndrome.
(Choice D) Most cases of hypertrophic cardiomyopathy are due to mutations in the genes encoding cardiac sarcomere proteins.
(Choice E) Cirrhosis of the liver is not associated with PCD.
Educational objective:
Primary ciliary dyskinesia results from an autosomal recessive mutation in the proteins responsible for normal flagellar and ciliary structure and function (eg, dynein, assembly proteins). Clinical manifestations include situs inversus, chronic sinusitis, bronchiectasis, and infertility.
