CA LÂM SÀNG 23

Major takeaway
Cystadenocarcinoma is a malignant ovarian neoplasm that is derived from glandular epithelium and typically occurs in postmenopausal women. It has two types, serous cystadenocarcinoma, which is the most common malignant ovarian cancer and often occurs bilaterally, and mucinous cystadenocarcinoma, which is typically unilateral and presents with pseudomyxoma peritonei.
Main explanation
Cystadenocarcinoma is a type of malignant ovarian neoplasm that is derived from glandular epithelium and typically occurs in postmenopausal women. It has two types, serous cystadenocarcinoma, which is the most common malignant ovarian cancer and often occurs bilaterally, and mucinous cystadenocarcinoma, which is typically unilateral and presents with pseudomyxoma peritonei (an intraperitoneal accumulation of mucinous substance from the cancer). When it metastasizes throughout the peritoneal cavity, individuals may present with ascites. The tumors appear to consist of complex cysts with a shaggy lining. Risk factors include positive family history and genetic predisposition in addition to conditions that increase lifetime estrogen exposure, such as advanced age, early menarche, late menopause, and nulliparity.

Dysgerminomas are malignant ovarian neoplasms that most commonly present in adolescents and appear as sheets of “fried-egg” cells on histology. Laboratory studies show elevated human chorionic gonadotropin and lactose dehydrogenase. They are rare (1% of ovarian cancers).

Granulosa cell tumors are the most common malignant stromal ovarian neoplasms. They often are functional and produce estrogenand/or progesterone, which may result in breast tenderness and postmenopausal bleeding. Histology shows Call-Exner bodies.

Immature teratomas are aggressive malignant ovarian neoplasms that are often diagnosed before the age of 20. They contain fetal tissue such as embryonic neural tissue.

Yolk sac tumors are aggressive malignant ovarian neoplasms that are solid, yellow, friable masses. Histology shows Schiller-Duval bodies which resemble glomeruli. Laboratory studies show elevated alpha-fetoprotein.

Major takeaway
5-α reductase inhibitors block the conversion of testosterone into dihydrotestosterone (DHT) and are first line therapy for hematuria secondary to benign prostatic enlargement.
Main explanation
5-α reductase inhibitors block the conversion of testosterone into dihydrotestosterone (DHT), which has stronger stimulatory effects in the prostate. They are the first line therapy for hematuria secondary to benign prostatic enlargement, leading to resolution or improvement in up to 90% of cases. These drugs also have a role in the management of patients with lower urinary tract symptoms who have prostate volume >40 g and/or PSA >1.6 ng/ml. In these patients, they not only lead to a greater symptomatic improvement, but also reduce the chances of disease progression (defined as the development of acute urinary retention or requiring surgical intervention). Transurethral resection of the prostate is a second-line therapyfor patients whose symptoms fail to improve with a 5-α reductase inhibitor.

While a suprapubic catheter would resolve this patient’s symptoms, there are other less invasive and less permanent options which can be trialled first.

Radical prostatectomy has no role in the management of hematuria due to benign prostatic enlargement. Radical prostatectomy is occasionally indicated in prostate cancer.

Transurethral resection of the prostate is a second-line therapy for patients whose symptoms fail to improve with a 5-αreductaseinhibitor.

Antibiotics have no role in the treatment of benign prostatic hyperplasia in the absence of infection. Signs and symptoms of infection include fever, and dysuria.

In older patients with sudden vision loss in one eye associated with a headache, you must consider giant-cell arteritis (GCA). Patients with GCA should be treated with steroids to decrease inflammation and prevent both vision loss in the other eye, and other ischemic events in the CNS.

Suspect a cerebrovascular accident (a stroke) when sudden onset neurologic symptoms can be localized to a single area of brain or brainstem tissue, especially when that region is fed by a single blood supply (e.g. the middle cerebral artery).

Major takeaway
Multiple sclerosis (MS) is characterized by a series of central nervous system lesions disseminated in time and space. MS is an autoimmune disease of inflammation, demyelination(loss of oligodendrocytes), and axonal loss.

Main explanation
A series of CNS lesions disseminated in time and space is classic for multiple sclerosis (MS). MS is a disease of inflammation, demyelination, and axonal loss. Because MS involves the CNS, demyelination occurs via the destruction of oligodendrocytes. It is the most common autoimmune disease of the CNS, and typically manifests in women in the late twenties to early thirties. It can be exacerbated by warm temperatures (Uhthoff’s phenomenon) and is associated with a myriad of neurological symptoms.
This patient’s main presenting symptoms constitute a classic description of optic neuritis. Optic neuritis typically manifests as the acute onset of decreased visual acuity associated with a relative afferent pupillary defect (RAPD). It may also be preceded by pain around the soon to be affected eye. An RAPD is a telltale sign of optic nerve disease and is diagnosed by checking pupillary light reactions. The pupil of the affected eye has no direct response– does not constrict to light shined directly upon it – but does have a consensual response – constricts when light is shined in the contralateral eye. This finding is sometimes characterized using the “swinging flashlight test.” See the attached video.

Guillain-Barré Syndrome (GBS) is an autoimmune attack on the myelin sheath of the peripheral nervous system (Schwann cells). Classical GBS affects the lower extremities first with flaccid weakness and progressive loss of reflexes. These symptoms progress cranially and eventually involve the arms and facial nerves.

Optic disc swelling has a number of etiologies, including optic nerve inflammation (as in this patient). When it is bilateral and associated increased intracranial pressure, it is called papiledema.

Nephrolithiasis, or renal calculi, is characterized by acute onset of severe, colicky flank pain, sometimes with nausea and vomiting. Urinalysis shows gross or microscopic hematuria.

Acute tubular necrosis (ATN) is associated with renal ischemia caused by shock, sepsis, or crush injuries causing myoglobinuria, and medications that decrease renal blood flow. ATN is most commonly associated with granular (muddy brown) casts.

Allergic interstitial nephritis (AIN) affects the interstitium of the kidneys. Causes of AIN include infections, reaction to medications such as nafcillin or methicillin, NSAIDs, rifampin, sulfa drugs, quinolones, diuretics, and allopurinol. It is characterized by dysuria, nausea, vomiting, fatigue, malaise, weight loss, hyperkalemia, metabolic acidosis, eosinophilia, rash, and urinary leukocytes.

Major takeaway
Alport syndrome is asymptomatic hematuria associated with deafness and eye disorders. Renal biopsy results may show glomerular basement membrane splitting due to a defect in collagen type IV production leading to problems in the kidneys, inner ear, and eyes.

Main explanation
Alport syndrome is a hereditary form of glomerulonephritis that usually presents in boys between the age of 5-20. The classic presentation of Alport syndrome is asymptomatic hematuria associated with deafness and eye disorders. Alport syndrome is a genetic cause of nephritic syndrome, which is a disorder of glomerular inflammation, also called glomerulonephritis. Nephritic syndrome is characterized by hematuria and red blood cell castsin the urine. Proteinuria may be present, but is usually <3.5 g/day. Other findings for nephritic syndrome include oliguria, macroscopic/microscopic hematuria, hypertension, and edema.

The classic presentation of Alport syndrome is asymptomatic hematuria associated with deafness and eye disorders. Renal biopsy results may show glomerular basement membranesplitting. It leads to progressive renal failure requiring renal transplant surgery. This disorder is due to a defect in collagen type IV production leading to problems in the kidneys, inner ear, and eyes.

Focal segmental glomerulosclerosis (FSGS) is a cause of nephrotic syndrome. FSGS may be idiopathic or associated with IV drug use, obesity, and HIV. Urinalysis shows microscopic hematuria and biopsy shows sclerosis in the renal capillary tufts.

Sheehan syndrome is a hypopituitarism caused by ischemic necrosis due to blood loss and hypovolemic shock during and after childbirth.

Major takeaway
Asherman syndrome is characterized by adhesions of the endometrium, and is most often associated with repeated dilation and curettage of the intrauterine cavity. It can result in hypomenorrhea, amenorrhea, and occasionally, infertility.

Main explanation
Asherman syndrome is the name given to the scarring of the uterine cavity. Women who undergo dilatation and curettage procedures are at risk of developing it. It is due to a severe pelvic infection unrelated to surgery. Intrauterine adhesions are often the result of this infection.

Remember that the uterine cavity is lined by endometrium, which is composed of 2 layers. Of these 2 layers, the basal layer is the one necessary for regeneration of the endometrium. In Asherman syndrome, this layer is damaged (from the D&C procedures – though it is not a common complication).

This results in adhesions of the uterine cavity and may cause hypomenorrhea, amenorrhea, and occasionally, infertility.

Premature menopause is a cause of secondary amenorrhoea. Infertility is the result of this condition, and the patient would most likely not have been able to conceive.

At this point a prolactinoma does not answer the findings presented by the vignette. There is no relationship between a dilation and curettage procedure and a prolactinoma. Laboratory examinations could be ordered to rule out any other possible diagnoses including prolactinoma.

Mayer-Rokitansky-Kuster-Hauser syndrome is also known as Mullerian agenesis. Patients with Mullerian agenesis will lack the presence of a uterus. The lack of a uterus would not allow a pregnancy to have occurred.

Major takeaway
Patients with carpal tunnel syndrome can suffer problems such as impingement, displacement, or inflammation that may affect the median nerve, resulting in altered sensations such as numbness and “pins and needles” on the lateral side of their hand.

Main explanation
Carpal tunnel syndrome is a result of the compression of the median nerve as it passes through the carpal tunnel. It is a clinical diagnosis that is based on signs and symptoms that are consistent with median nerve injury of the hand.
The median nerve supplies the sensory innervation of the lateral half of the palm and the first 3.5 digits. Thus patients with carpal tunnel syndrome have altered sensations such as numbness and “pins and needles” on the lateral side of their hand. The median nerve also innervates the thenar muscles, which includes the abductor pollicis brevis, flexor pollicis brevis, and opponens pollicis. This explains why this patient presented with wasting of the thenar muscles and weakness in the movement of the thumb, although they do not always have this presentation. Tinel sign and Phalen maneuver are both physical examination techniques done to confirm the diagnosis of carpal tunnel syndrome. Both tests are ways to detect irritated nerves and should be positive in patients with carpal tunnel syndrome. As can be seen in the image below, the ulnar nerve is not affected in carpal tunnel syndrome as it runs superficial to the tunnel.

While the median nerve is injured in carpal tunnel syndrome due to increased pressure and a degree of ischemia, a laceration of the nerve would cause more severe symptoms than numbness and pain.

The paresthesia on the lateral hand and wasting of thenar muscles are both consistent with median nerve injury. Radial nerve palsy, also known as wrist drop, occurs when a person cannot extend their wrist and it hangs flaccidly.

The paresthesia on the lateral hand and wasting of thenar muscles are both consistent with median nerve injury. The ulnar nerveprovides sensory innervation to the medial side of the hand and innervates the hypothenar muscles, as well as the majority of muscles of the hand.

The paresthesia on the lateral hand and wasting of thenar muscles are both consistent with median nerve injury. The ulnar nerveprovides sensory innervation to the medial side of the hand and innervates the hypothenar muscles, as well as the majority of muscles of the hand.

Appendicitis is caused by obstruction of the appendiceal lumen, most commonly due to inflammatory bowel disease, infections, fecal stasis, parasites, or foreign bodies.

Although pregnancy is a risk factor for developing cholesterol cholelithiases, asymptomatic bacteriuria is not associated with an increase of their development.

Inflammation of the colon can be caused by a variety of factors, including infection, hypersensitivity to various allergens, ischemia, vasculitis, or some drugs.

Pancreatitis can be acute or chronic. Acute pancreatitis is most commonly caused by long-term alcohol use and biliary stonedisease, while chronic pancreatitis is usually due to metabolic changes.

Major takeaway
Asymptomatic bacteriuria occurs in 2-7% of pregnancies. Pyelonephritis is the most common complication and occurs in 20-40% of untreated cases, therefore it must be treatedimmediately.
Main explanation
The patient’s presentation and laboratory findings are consistent with asymptomatic bacteriuria (ABU), which occurs in 2-7% of pregnancies. ABU is diagnosed in a patient who has a positive urine culture but lacks symptoms of a urinary tract infection (UTI), such as dysuria, urgency, frequency, or hesitancy. Criteria for asymptomatic bacteriuria include urine culture showing a single bacterial species with >100,000 colonies from a voided urine specimen, or >100 colonies from a catheter specimen, or Group B Streptococcus bacteria at any count. Pyelonephritis is the most common complication and occurs in 20-40% of cases of untreated bacteriuria.

It is important to remember that ABU is always treated during pregnancy because it is more likely to lead to cystitis and pyelonephritis in pregnant women. This phenomenon is due to physiological changes that occur in the renal and urinary collecting system during pregnancy that promote urinary stasis (progesterone-induced decrease in urethral tone and motility). This patient should be treated with a 10-day course of antibiotics. Urine culture should be repeated one month after treatment. Common first line antibiotics in pregnancy include nitrofurantoin, cephalexin, and cefuroxime.

Major takeaway
Lordosis refers to the inward curvature of the lumbar spine, which is normal. Pathologic increases in lordosis can occur with repetitive hyperextension, as is associated with dancing and gymnastics.
Main explanation
The patient presents with a history of chronically worsening low back pain and posture changes characterized by exaggeration of the stomach. Collectively, these symptoms suggest marked lumbar lordosis. While some degree of lordosis, or the inward curve of the lumbar spine above the buttocks, is normal, pathologic lumbar lordosis can cause pain and altered posture. In particular, the repetitive hyperextension motions of dancing and gymnastics may be associated with increased lumbar lordosis. In severe cases, patients will appear to be puffing out the stomach and buttocks. This patient should undergo further studies to measure the lumbar curvature and rule out fractures or other possible causes.

Osteoarthritis is a common cause of low back pain but is typically seen in patients over the age of 40. In addition, osteoarthritisdoes not explain the posture changes the patient describes.

Osteoporosis can lead to vertebral compression fractures, which can cause the acute onset of severe back pain; however, osteoporosis is unlikely in an otherwise healthy young adult.

Radiculopathy, which results from damage to a spinal nerve root, typically causes pain, sensory loss, weakness, and/or reflex changes. Most cases involve L5 or S1.

Spinal stenosis classically presents with pain that is localized to the calf and distal lower extremity, exacerbated by walking and alleviated by sitting or leaning forward.

Childbirth-related post-traumatic stress disorder is a well-described subset of posttraumatic stress disorder (PTSD). Patients may experience intrusive symptoms such as flashbacks and nightmares, as well as symptoms of avoidance, problems in developing a mother-child attachment, not having sex in order to prevent another pregnancy, and avoidance of birth and pregnancy-related issues.

40-80% of postpartum women develop mild mood changes. However, this patient has symptoms of postpartum depression(PPD), which affects approximately 10% of women. A history of depression either prior to or during pregnancy is the primary risk factor.

Postpartum blues is a transient condition characterized by mood swings ranging from elation to sadness, irritability, anxiety, decreased concentration, insomnia, tearfulness, and crying spells. These symptoms typically begin within two to three days of delivery and resolve within two weeks.

Major takeaway
Postpartum depression affects approximately 10% of postpartum women. It is characterized by severe depressive symptoms that last and worsen for more than two weeks after delivery.

Main explanation
Postpartum depression (PPD) affects approximately 10% of women. A history of depressioneither prior to, or during pregnancy is the primary risk factor. PPD is characterized by changes in sleep, energy level, appetite, weight, and concentration. Additionally, mothers with PPD may feel overwhelmed and unable to care for the baby or feel that they are not bonding with their baby. Recommended treatment for PPD includes psychotherapy and pharmacotherapy with selective serotonin reuptake inhibitors.

Actress Brooke Shields spoke out about her battle with postpartum depression after the birth of her first child. She also wrote a book, Down from the Rain, which chronicled her experiences and raised public awareness for postpartum depression.

Postpartum psychosis is characterized by onset within two weeks of childbirth with a combination of psychotic symptoms (e.g. hallucinations and delusions) and symptoms of a mood disorder. Women with postpartum psychosis are at increased risk of harming their baby. Hospitalization may be appropriate and be considered on a case-by-case basis.

The reaction to a bee sting would be an example of an anaphylactic reaction, which is a type I hypersensitivity. Type I hypersensitivity is mediated by IgE.

Henoch-Schonlein purpura is an immune complex type III hypersensitivity with IgA deposits in blood vessels. In the skin, the disease causes palpable purpura (small hemorrhages), often with joint and abdominal pain.

Contact dermatitis due to poison ivy is an example of a type IV delayed hypersensitivity. Type IV delayed hypersensitivity is a cell mediated process.

A positive purified protein derivative (PPD) test is an example of a type IV delayed hypersensitivity. Type IV delayed hypersensitivity is a cell mediated process.

Major takeaway
Graves’ disease is caused by a type II hypersensitivity reaction. The disease results from an antibody, called thyroid stimulating immunoglobulin (TSI), that has a similar effect to thyroid stimulating hormone (TSH). These antibodies cause the thyroid gland to produce excess thyroid hormone.
Main explanation
Hemoptysis and hematuria are two of the presenting symptoms of Goodpasture’s syndrome, which is this patients diagnosis. This condition develops via a type II hypersensitivity reactionwith antibodies to the glomerular basement membrane. The finding of linear deposits on immunofluorescence helps to confirm the diagnosis. Of the choices listed, only Graves’ diseaseis a type II hypersensitivity reaction.

Graves’ disease results from an antibody, called thyroid stimulating immunoglobulin (TSI), that has a similar effect to thyroid stimulating hormone (TSH). These antibodies cause the thyroid gland to produce excess thyroid hormone. The diagnosis may be suspected based on symptoms with blood tests and radioiodine uptake used to confirm the disease. Typically blood tests show a raised T3 and T4, and low TSH. Increased radioiodine uptake is seen in all areas of the thyroid, and TSI antibodies are also found on serum testing.