CA LÂM SÀNG 14

Paclitaxel has not been found to be effective in neurological tumours. It is used as chemotherapy for lung and breast cancer, among others. It is a taxane that stabilizes the microtubules and prevents their disassembly.

Temozolomide is typically indicated for second-line chemotherapy of oligodendrogliomas and gliomas. It is an alkylating agent with the main side effect of bone marrow suppression.

Radiotherapy is not typically used in the treatment of meningioma. Brachytherapy is used in the treatment of breast, prostate, skin, and cervical cancer.

Major takeaway
Suspect meningioma in a young or middle-aged patient who presents with focal frontal lobesymptoms, headache, and a finding of a distinct contrast-enhancing mass on imaging.
Main explanation
This patient is presenting with symptoms typical of a left frontal lobe lesion, such as weakness of the contralateral lower extremity and personality changes. Furthermore, she has headaches, though without worrying signs of increased intracranial pressure. In a younger-middle-aged woman, the most likely diagnosis that correlates with the mass seen on her CT imaging is a meningioma. This a tumour arising from the cells of the meninges, the layers of tissue covering the brain. The vast majority of meningiomas are benign in nature. Thus, treatment for meningiomas relies heavily upon complete surgical resection. Without complete surgical resection, the tumour may recur. While active surveillance is an option in asymptomatic or minimally symptomatic patients with meningioma, in this scenario, the symptoms are significant enough that surgical resection is warranted.

Radiotherapy is not typically used in the treatment of meningiomas. External beam radiotherapy is used to treat other primary or metastatic brain tumors.

Follicular carcinoma is a type of thyroid cancer that accounts for 15% of thyroid cancer. Thyroglobulin is often used as a tumor marker. Follicular cells are the thyroid cells responsible for the production and secretion of thyroid hormones.Here, however, the histological findings are not characteristic of follicular carcinoma.

Anaplastic thyroid carcinoma is a type of thyroid cancer which has a very poor prognosis due to its aggressive behavior and resistance to cancer treatments. Its anaplastic cells have poor differentiation. Here, however, the cells have a good differentiation, in fact, they have optically clear nuclei.

Medullary thyroid carcinoma is a type of thyroid cancer which originates from the parafollicular cells, that produce the hormone calcitonin. Medullary tumors are the third most common of all thyroid cancers. Because of calcitonin dysregulation, calcium metabolism is also altered, and so, patients often have abnormal levels of calcitonin, which is not seen in this patient.

Lymphoma is a blood cell tumor that develops from lymphocytes. Patients often present with enlarged lymph nodes, fever, drenching sweats, unintended weight loss, itching, and constantly feeling tired. Although this patient has risk factors to develop lymphoma, the histological findings are characteristic of papillary thyroid cancer.

Major takeaway
Papillary thyroid cancer is the most common type of thyroid cancer. Tissue biopsy is characterized by “Orphan Annie” eyes, psammoma bodies, and nuclear grooves. Patients are typically asymptomatic and this particular type of cancer is usually discovered on routine examination as a painless neck mass.
Main explanation
The patient in the vignette is experiencing papillary thyroid cancer. Papillary thyroid cancer is the most common type of thyroid cancer. Tissue biopsy usually shows empty-appearing nuclei with central clearing, known as “Orphan Annie” eyes. Another classic histological findings is psammoma bodies (dystrophic calcifications in cancer cells) and nuclear grooves.

Patients are typically asymptomatic and this particular type of cancer is usually discovered on routine examination as a painless neck mass. Sometimes, the mass may produce local symptoms (i.e., voice hoarseness, damage to recurrent laryngeal nerve.). High-risk individuals are those with RET and BRAF mutations and those who suffered irradiation during childhood. The mainstay of treatment for papillary thyroid cancer is surgery, the initial procedure is usually a total thyroidectomy.

Aspergers syndrome would have dissimilar hand movements than those described in this patient. They would be more simple, bilateral, intermittent and more often involving objects.

Autism disorder would have dissimilar hand movements. They would be more simple, bilateral, intermittent and more often involving objects. Hand stereotypes in Rett Syndrome are predominantly complex, continuous, localized to the body mid-line, and involve mouthing. However, in Autism spectrum disorder, hand stereotypes are simple, bilateral, intermittent and often involving objects.

Chorea, bruxism and dystonia are shared between cerebral palsy and Rett syndrome, however, developmental milestone regression as seen in Rett syndrome would be unusual in cerebral palsy.

Major takeaway
Hand stereotypes in Rett syndrome are predominantly complex, continuous, localized to the mid-line and involve mouthing or wringing motions. Children with Rett syndrome typically have normal early growth and development, and it almost exclusively affects girls.

Main explanation
This patient has Rett syndrome. The types of hand movements displayed by the patient help to make this diagnosis. Decelerated head growth is also a common feature.
A child with autism or Asperger syndrome would have different hand movements. They are generally simple, bilateral, intermittent and more often involve objects.
Hand stereotypes in Rett syndrome are predominantly complex, continuous, localized to the mid-line and involve mouthing or wringing motions.
Dyskeratosis congenita is a rare progressive congenital disorder, that resembles premature aging and affects the integumentary system.
Incontinence, screaming fits, loss ofspeech, sensory problems, breath holding, hyperventilationand air swallowingare shared signs of both autism and Rett syndrome.Chorea, bruxism and dystonia are notpresent in autism disorder, only in Rett syndrome. However, these signs couldalso be present in a patient with cerebral palsy.

Dyskeratosis congenita is a rare progressive congenital disorder, that resembles premature aging and affects the integumentary system. Dyskeratosis congenita is characterized by the triad of reticulated skin hyperpigmentation, nail dystrophy, and oral leukoplakia.

Candida albicans is an opportunistic fungi that can cause candidiasis in infants and immunodeficient individuals. Candiasis is characterized by a cottony feeling in the mouth, loss of taste, dysphagia, and white oral plaques. A potassium hydroxide preparation of the scrapings can be used to diagnose candidiasis.

Group B Streptococcus (GBS), or Streptococcus agalactiae, can cause meningitis, pneumonia, and sepsis in neonates or young infants. Transmission occurs at birth, as GBS can colonize the genital tract of pregnant women. GBS is beta-hemolytic and bacitracin-resistant.

Major takeaway
Streptococcal pharyngitis is caused by group A Streptococcus, which is gram-positive, beta-hemolytic, and bacitracin-sensitive. It is characterized by an exudative pharyngitis.
Main explanation
Streptococcal pharyngitis is the most common form of pharyngitis and caused by group A Streptococcus (GAS), or Streptococcus pyogenes. GAS is a gram-positive cocci with a hyaluronic acid capsule. It is beta-hemolytic, meaning that growth on sheep blood agar plates will show a golden clearning around each colony due to complete breakdown of heme. Alpha-hemolysis manifests as a green clearing due to incomplete hemolysis yielding biliverdin. Gamma-hemolysis refers to the absence of hemolysis. GAS is additionally bacitracin-sensitive, a feature that distinguishes it from Group B Streptococcus. GAS pharyngitis is characterized by an exudative pharyngitis accompanied by fever, vomiting, tender cervical lymph nodes, palatal petechiae, and scarlatiniform rash. It can be diagnosed with throat culture. Penicillin is the first-line treatment.

Epstein-Barr virus (EBV) is the cause of infectious mononucleosis, which is characterized by headache, malaise, low-grade fever, pharyngitis, and cervical lymphadenopathy. Viruses like EBV do not grow on blood agar.

Rhinovirus is a single-stranded RNA virus that is a common cause of upper respiratory infections (URIs). It is a member of the picornavirus family. Rhinovirus URI is characterized by rhinorrhea, cough, nasal obstruction, and sore throat. Rhinovirus does not grow on blood agar.

This drug is a selective estrogen receptor modulator (SERM) used to treat osteoporosis and breast cancer.

A weak synthetic androgen used to treat endometriosis and hereditary angioedema.

This is used alone to treat hypogonadism or ovarian failure, androgen-dependent prostate cancer in men, or for hormone replacement therapy in postmenopausal women. It is also the estrogen component used in combination with progestinsin many oral contraceptive preparations. Since this patient has low levels of GnRH, LH, FSH, and estrogen, rather than just estrogen, we can assume that her ovaries are not the source of her infertility.

This is an aromatase (conversion of testosterone to estrogen) inhibitor used to treat breast cancer in postmenopausal women.

Major takeaway
Clomiphene is used for the treatment of ovulatory function in women desiring pregnancy. It works at the level of the hypothalamus binding to estrogen receptors inhibiting the normal negative feedback loop of estrogen. This results in increased pulsatile GnRH secretion and subsequent FH and LH release causing growth of the ovarian follicle.
Main explanation
If the hypothalamus is overly sensitive to estrogen, there will be excessive feedback inhibition causing decreased GnRH release, which will lead to low FSH and LH release by the anterior pituitary and ultimately decreased estrogen levels. This may be corrected by administering clomiphene, which blocks estrogen-mediated feedback inhibition of GnRHrelease in the hypothalamus. This allows for increased release of FSH, LH, and estrogen, increasing the likelihood of ovulation.

Major takeaway
Fetal alcohol syndrome (FAS) is characterized by microcephaly, smooth philtrum, cardiac septal defect, small palpebral fissure, midfacial hypoplasia, and microphthalmia.

Main explanation
Fetal alcohol syndrome is a very common cause of mental and growth retardation. Characteristic findings are microcephaly, smooth philtrum, cardiac septal defect, small palpebral fissure, midfacial hypoplasia, and microphthalmia.

Fetal alcohol spectrum disorders (FASD) are a group of conditions that can occur in a person whose mother drank alcohol during pregnancy. Those affected are more likely to have trouble in school, legal problems, participate in high-risk behaviors, and have trouble with alcohol or other drugs. The most severe form of the condition is known as fetal alcohol syndrome (FAS).

There is no cure for FASD, but treatment is possible. Because CNS damage, symptoms, secondary disabilities, and needs vary widely by individual, there is no one treatment type that works for everyone. Psychoactive drugs are frequently tried on those with FASD as many FASD symptoms are mistaken for or overlap with other disorders, most notably ADHD. Behavioral interventions are based on the learning theory, which is the basis for many parenting and professional interventions.

Diazepam is a benzodiazepine medication that is used in the treatment of seizures and occasionally anxiety. Prenatal exposure may cause a cleft lip/palate.

Lithium causes Ebstein’s anomaly. Ebstein’s anomaly is a congenital heart defect in which the septal and posterior leaflets of the tricuspid valve are displaced towards the apex of the right ventricle of the heart.

Thalidomide causes flipper-like appearance of hands known as phocomelia. Thalidomide is no longer used for the treatment of morning sickness as a result of this teratogenic activity.

Valproic acid is a common treatment for epilepsy. Patients on this medication should have it changed prior to pregnancy because it causes spinal defects.

Exogenous surfactant (e.g. Survanta), or perfluorocarbon aerosol, are used for the treatment of infant respiratory distress syndrome (IRDS), which appears in premature infants and is caused by developmental insufficiency of surfactant production and structural lung immaturity.

Hepatitis B vaccine prevents hepatitis B and the first dose is recommended within 24 hours of birth, with either two or three more doses given after that. This includes those with poor immune function such as from HIV/AIDS and those born prematurely.

Phototherapy consists of exposure to daylight or to specific wave lengths of light using polychromatic polarised light, lasers, light-emitting diodes, fluorescent lamps, dichroic lamps or very bright, full-spectrum light. One common use is for the treatment of skin disorders, chiefly psoriasis, acne vulgaris, eczema, and neonatal jaundice.

Major takeaway
Place infant in supine position for sleeping is one of the most effective methods for preventing sudden infant death syndrome (SIDS), which is the sudden unexplained death of a child less than one year of age. Other measures include a firm mattress separated from but close to caregivers, among others.

Main explanation
Sudden infant death syndrome (SIDS) is the sudden unexplained death of a child less than one year of age. Diagnosis requires that the death remains unexplained even after an autopsy, exploration of the medical history of the infant and family, and detailed death scene investigation. SIDS occurs during sleep most of the times. The exact cause of SIDS is unknown. The combination of factors including sleeping on the stomach or side, overheating, exposure totobacco smoke, accidental suffocation, being born before 39 weeks’ gestation, infections, genetic disorders, heart problems, or child abuse, is proposed as a possible cause of SIDS. The most effective method of preventing SIDS is putting a child less than one year of age on their back to sleep. Other measures include a firm mattress separated from but close to caregivers, no loose bedding, a cool sleeping environment, using a pacifier, and avoiding exposure to tobacco smoke. Breastfeeding and immunization are also preventive. Measures not shown to be useful include positioning devices and baby monitors.

As a result of the occurrences of vitamin K deficiency bleeding, the Committee on Nutrition of the American Academy of Pediatrics, has recommended the administration of 0.5 to 1.0 mg of vitamin K1 to all newborns shortly after birth.

Regardless of the findings on pelvic examination in this patient a pregnancy test will still be required to assess the risk of ectopic pregnancy.

A transvaginal pelvic ultrasound is part of the work up for ectopic pregnancy however a pregnancy test should be done first to confirm that this is a possible diagnosis.

A urinalysis and culture is unlikely to provide useful information in a patient presenting with vaginal bleeding and abdominal pain. The most useful urinary result would be a urinary pregnancy test.

Major takeaway
The classic triad for ectopic pregnancy is abdominal pain, vaginal bleeding, and a missed menstrual cycle. Remember the clinical pearl: “all female patients of reproductive agepresenting with abdominal pain are pregnant until proven otherwise” and an objective pregnancy test is required in all patients.

Main explanation
This girl is presenting with the classic triad for ectopic pregnancy: abdominal pain, vaginal bleeding, and a missed menstrual cycle. 50% of patients with ectopic pregnancypresent with all 3 symptoms. Regardless of how patients present, or their age, any female of reproductive age presenting with abdominal pain or unusual vaginal bleeding should be suspected of having an ectopic pregnancy until proven otherwise.

Other symptoms of ectopic pregnancy may be related to early pregnancy (nausea, breast fullness, constipation) or ectopic rupture (hemodynamic instability, dizziness or weakness, fever, vomiting) which warrants urgent surgical treatment.

Other possibilities on the differential diagnosis for this patient include appendicitis, ovarian cyst, ovarian torsion, normal pregnancy, threatened miscarriage, irritable bowel syndrome, Crohn’sileitis, UTI, and pelvic inflammatory disease. A careful history can be crucial to help with diagnosis. A pregnancy test would be the most important initial step to help guide management and rule in or out one of the most serious differentials: ectopic pregnancy.

A CT scan is contraindicated during pregnancy. This patient could have a viable pregnancy and be having a threatened miscarriage. US is the best imaging modality to investigate further but a pregnancy test is required first.

Colorectal cancer is the second most commonly diagnosed cancer in women and third most common in men. Cancer is infrequent before age 40, with 90 percent of cases occurring after 50 years. The AAFP recommends colorectal cancer screening with fecal occult testing, sigmoidoscopy, or colonoscopy between 50 and 75 years.

Major takeaway
Osteoporosis screening in women should begin at age 65. Dual-energy X-ray absorptiometry (DEXA) testing is the most widely used method for screening. Routine screening for men with no known risk factors has not been recommended.

Main explanation
Osteoporosis is a disease characterized by low bone density, resulting in increased risk of fracture. The American Academy of Family Physicians (AAFP) and the United States Preventive Services Task Force (USPSTF), recommend screening through bone mineral densitytesting in women greater than 65 years or in postmenopausal women younger than 65 year with clinical risk factors for fractures. Clinical risk factors for osteoporosis include advanced age, previous fracture, steroid therapy, low body weight, and current tobacco or excessive alcohol use.

Certain medications increase the rate of bone loss including some antiseizure medications, chemotherapy, proton pump inhibitors, selective serotonin reuptake inhibitors, and steroids. Not enough exercise and smoking are also risk factors. Osteoporosis is defined as a bone density of 2.5 standard deviations below that of a young adult. This is typically measured by dual-energy X-ray absorptiometry at the hip.

Breast cancer is the most common cancer in women, and the second deadliest cancer. The AAFP recommends routine screening every two years for women between ages 50 and74. Screening mammograms before 50 years may be indicated based on individual risk factors.

The Papanicolaou (Pap) smear screening test was the first widespread effort to detect cancer. The AAFP recommends screening for cervical cancer every 3 years by Pap smear in women between the ages of 21 to 65.

Colorectal cancer is the second most commonly diagnosed cancer in women and third most common in men. Cancer is infrequent before age 40, with 90 percent of cases occurring after 50 years. The AAFP recommends colorectal cancer screening with fecal occult testing, sigmoidoscopy, or colonoscopy between 50 and 75 years.

Major takeaway
Lambert-Eaton myasthenic syndrome is caused by antibodies to voltage-gated calcium channels. This decreases acetylcholine release from presynaptic neurons and causes muscle weakness.

Main explanation
Lambert-Eaton myasthenic syndrome (LEMS) is characterized by proximal muscle weaknessthat improves with use of the muscles. It is caused by antibodies to pre-synaptic voltage-gated calcium channels. This inhibits the release of acetylcholine from pre-synaptic neurons, thus decreasing muscle contraction. The more that specific muscle is used, the more acetylcholine builds up in the synapse and the less weakness the patient experiences. This is consistent with this patient’s presentation. LEMS is a paraneoplastic syndrome; about 50% of cases are associated with malignancy, the most common being small cell lung cancer.

LEMS can be difficult to distinguish from myasthenia gravis, which is caused by antibodies to acetylcholine receptors on postsynaptic neurons. However, one key difference is that in myasthenia gravis, weakness does not improve with use of the muscle.

This patient does have COPD; the characteristic findings of COPD on chest radiograph is flattening of the diaphragm and elongation of the mediastinum. However, an exacerbation does not cause proximal muscle weakness, and is not associated with lung nodules.

Myasthenia gravis is characterized by muscle weakness that worsens with use. In contrast to Lambert-Eaton syndrome, it often involves the eyelids. The edrophonium test is used for diagnosis. A myasthenic crisis may develop if the diaphragm and muscles of respiration are involved.

Although asthma may develop at any age, new-onset asthma is less frequent in older adults. Neither muscle weakness nor a radiographic nodule are characteristic.

Muscular dystrophy is another cause of muscle weakness, but it does not get better with use and is not associated with the lung findings.