USMLE CLASSIC CLUES

Leydig cell tumor

A combination that should alert us to the possibility of Leydig cell tumor where the interesting testicular tumor may also produce estrogen. Another clue is the description of rod shaped crystals in the tumor cells cytoplasm (what's called the Reinke crystals).

This tumor comes under different questions in the exams. Besides what was said: This is a testicular non -germ tumor. It is benign It is producing androgen It is the couse of precocious puberty in boys.

Psychotic patient with polydipsia A psychotic patient on phenothiazines therapy presents with polyuria, polydipsia and water deprivation test results in correction of urine osmolality. Answer: Phenothiazine cause severe dry mouth to the point that the patient develops primary polydispia

Hypertension and Adrenogenital syndromes If the case describes hypertension + increased adrenal androgen production such as hairsuitism and acne then think 11 Beta Hydorxylase deficiency If the case describes hypertension + decreased adrenal androgen production such as loss of hair then think 17 Alfa Hydroxylase deficiency Check your references and you will know why

Enzyme Deficiency Blood Pressure Virilization 11 B Hydroxylase 1(up) 1(up) 21 B hydroxylase 2(down) 1(up) 17 alpha hydroxylase 1(up) 7(down)

always 1(up) means (hypertension or hirsutism)

Eczema + Petichiae + Immunodeficieny The triad should unmistakeably makes us think of Wiskott-Aldrich syndrome. The USMLE may present for you a male child (because it's X linked recessive) with a very characteristic combination of eczema and petichiae (because of thromobocytopenia). Platelets are characterisitcally small with low mean platelet volume and there's immunodeficiency characterized by low IgM and high IgA and IgE levels. Propensity to develop autoimmune disorders and lymphoma/leukemia is there. keep this syndrome in your mind for the USMLE Step 1 and also for CK. JOB'S syndrome has a similar presentation too Eczema + Petichiae + Immunodeficieny but it has COLD ABCESSES.... USMLE may confuse u with it... It is characterized by recurrent "cold" staphylococcal infections, unusual eczema-like skin rashes, severe lung infections that result in pneumatoceles (balloon-like lesions that may be filled with air or pus or scar tissue) and very high concentrations of the serum antibody IgE. Inheritance can be autosomal dominant, or recessive, and autosomal dominant form of the disease; these patients have problems with their bones including recurrent fractures and scoliosis. Many patients with autosomal dominant hyper IgE syndrome fail to lose their primary teeth and have two sets of teeth simultaneously.

Animal Exposure and CNS radiograhic lesions! Pig farm neurocysticercosis characterized by multiple cysts with surprisingly less CNS symptoms Sheep farm Echinococcus granulosus, usually causing a single large cyst. Cats and dogs Toxoplasmosis, should show typical ring enhancement.

Mosquito bite cerebral malaria has but no radiologic findings. pica (dirt eating) visceral larva migrans (toxocara canis) may cause cerebral granulomas. Adolescent with fatigue An adolescent with fatigue, fever and his girlfriend has similar symptoms few weeks ago Think Infectious Mononucleosis "Kissing Disease" n women the most common location for ulcers is the outer lips of the vagina (labia majora). "Kissing ulcers" may develop. These are ulcers that occur on opposite surfaces of the labia

55 Yr Old Smoker If you ever face a question telling you about an over 55 yr old male or female smoker and alcoholic living in a poorly maintained and air condition environment and developed pneumonia then you have to start thinking of Legionnaire's Disease Other clues might be Positive Silver stain Use of Charcoal Yeast Extract growth medium Immunocompramised patient And atypical X ray findings Exclusively Breast Fed Exclusively Breast Fed Baby + Born overseas or born at home Think Vitamin K deficiency as no injection was given and the breast milk is deficient in Vitamin K Alzheimer disease sudden death If the question stem describes an elderly patient with history of Alzheimer disease who suddenly dies or suffered stroke then think Cerebral Amyloid Angiopathy This is the same amyloid deposited in neurones in Alzheimer patients gets deposited in the blood

vessels media and render them friable. So there will be a risk of sudden severe hemorrhagic stroke that may kill the patient on the spot. The other name for cerebral amyloid angiopathy is cerebral congophilic angiopathy, the latter name stems from the fact that amyloid stained with congo red stain.

Hypercalcemia + Hilar lymphadenopathy Although in clinical practice we tend to put sarcoidosis on the bottom of the list, in USMLE you should highly suspicious of this diagnosis. Classically, they'll say Middle aged person presented with chronic dry cough, plus some abnormal central CXR finding (hilar lymphadenopathy) and perhaps they give you an elevated level of Calcium in the blood. Such a scenario should immediately makes you think of sarcoidosis and then the question can about the following:

Non caseating granuloma Use of steroids in the treatment Mikulicz syndrome Elevated ACE levels Schaumann bodies and Asteroid bodies

Fever + Parotitis + Uveitis + Bell's Palsy! The combination of low grade fever with parotid enlargment and eye uveitis and facial nerve palsy should alert us to the possibility of Heerfordt-Waldenstrom syndrome which is one of the presentations of Sarcoidois. The biggest confusing differential diagnosis would be Sjgrens syndrome as these may be patients frequently fave fever, parotid enlargment, joint, and eye disease. However, the presence of hilar lymphadenopathy and the Bell's palsy are clear distinguishing features of this special sarcoid presentation.

Hypotonia + Jaundice + Seizures + MR If the case indicates an infant who shortly after birth develops jaundice, hepatomegaly, intractable seizures, facial abnormalities, hypotonia, developmental delay and later mental retardation, vision and hearing abnormalities, and deterioration of renal function then we have to

think of Zellweger syndrome. Zellweger syndrome is an autosomal recessive disorder in which there's abnormal development of peroxisomes which are the cellular organelles responsible for beta oxidation of very long chain fatty acids.

Vaginal discharge + RUQ pain One of the classic case scenarios seen in USMLE is the description of the a premenopausal female with h/o multiple sexual partners, vaginal discharge, fever, and suprisingly an right upper abdominal pain. This is a classic presentation of Fitz Hugh Curtis Syndrome in which the infection ascends from a PID (typically salpingitis) to involve the capsule of the liver and therefore pain may sometimes refer to the right scapula and tip of shoulder. Hypogonadism + Anosmia Kallman syndrome which is due to hypothalamic defect in producing GnRH and thereby causing hypogonadotrophic hypogondism and a congenital loss of smell (Anosmia) is a characterisitc syndrome that is commonly asked about in the USMLE. Low LH, Low FSH, Low Testosterone, Males and females, & Normal stature (as opposed to Klinefilter) are other features of Kallman.

Child + Ataxia + Mural Nodule = ? Classic case scenario in USMLE where a child or a young adult presents with cerebellar ataxia and other cerebellar signs + headache + CT scan or MRI showing a cystic lesion with "mural nodule" then your diagnosis should be Pilocytic Astrocytoma which is a grade I astrocytoma with favorable prognosis. It's the most common primary CNS in children followed by craniopharyngioma and ependymoma.
Astorcytoma is the most common tumor in Children.

Delayed Umbilical Sloughing The title of this message could well constitute a buzzword. It's a very classical description of the autosomal recessive disorder Leukocyte Adhesion Deficiency. Newborns presents with omphalitis and delayed sloughing with frequent bacterial infections. However, abscesses do not occur as the neutrophils lack the ability to adhere to the endothelium because of a defective integrin molecule also called CD18.

More specifically the defective gene (on chromosome 21) encodes for beta2 integrin subunit that is found in all three integrin molecules namely LFA1, MAC1, and VLA4. Once the diagnosis is suspected a series of immune tests carried until finally the CD18 is found missing. One of the characteristics of the disease is the extreme leukocytosis seen in this patient as the neurtrophils are unable to leave the blood vessels. It's important not confuse CD18 with CD34, CD34 is present on the endothelial surface of venules and it binds the L-selectin on T lymphocytes calling them to home in (circulating Naive lymphocytes either find their target antigen or go HOME via the process of homing into secondary lymphoid). organs).

Southwest Desert Infections USMLE Step 1 typically plays with you by throwing a case in which the patient is living in the southwest desert states such as California, Colorado, New Mexico, Arizona, Nevada, and Utah. Your Differential Diagnosis should include the following:

Yersinia pestis (Plague) Coccidioides immitis (San Joaquin Valley Fever) Hanta virus

To add more difficulty they typically give a pneumonia-like or flu-like syndrome and inhalational mode of transmission both can be seen in all of these infections! What is even more confusing is that both plague and Hanta virus may be transmitted from rodent feces and urine such as mice! Distinguishing between these are the following points:

Plague: bipolar staining yersinia, coagulase positive, V, W, and F-1 antigens, very high fever, conjunctivits, and hemorrhagic lymph nodes (buboes) with high mortality. Coccidioides: is unlike the two others is usually self limited unless in immune compramised patients. Other clues may include the desert bumps which are erythema nodosum and calcific pulmonary lesions and dimorphic fundus with unique spherules in the tissue form. Hanta virus: Progression to adult respiratory distress syndrome, then respiratory failure, then death.

Teen with Liver Problem + Personality Changes

If the question stem describes a child with signs of chronic liver disease such as bleeding tendency, signs of liver cirrhosis, jaundice, elevated LFTs, ...etc. Plus a noticeable change in behavior such as clumsiness or even some Parkinsonian symptoms. Think Wilson's Disease immediately. They may also show you this picture (click the thumbnail to enlarge)

This picture is copied from Wikimedia page

In addition to the Kayser Fleischer ring shown above, The question may ask about the mode of inheritance (autosomal recessive) or treatment (Pencillamine or liver transplantation) or lab abnormalities (decreased ceruloplasmin and increased urinary copper) and the gold standard for the diagnosis is Liver Biopsy.

Sickle Cell Trait Often tested in USMLE and perhaps more than the disease! Classic clues in the case are:

African American Developed dyspnea in Denver (high altitude) Sudden death after sustained prolonged exercise Rhabdomyolyis and red urine Renal papillary necrosis and sloughing Heterozygote Hemoglobin electrophoresis blot

Dementia + Gait Apraxia + Incontinence The combination of urinary incontinence, dementia (memory loss, confusion, etc) with gait apraxia (difficulty walking, ataxia, etc) is the classic triad seen in patients with Normal Pressure Hydrocephalus. This triad has been classically dubbed "Wet, Wacky, and Wobbly" ! Other clues could be No cortical atrophy, intermittent raised CSF pressure, no CSF block

Tinkly bowel sounds + distension Whenever you see a case of tinkly bowel sounds (exaggerated and sounds like a bell under water) + abdominal distension then think jejunal or ileal obstruction (not dudenal or large bowel). Common causes in adults include:

Hernias Adhesions Tumor Foreign body Meckle's diverticulum Crohn's disease Ascaris infection Midgut volvulus Intussusception

Postmenopausal Bleeding If the case tells you bleeding after menopause then it's Endometrial Carcinoma until proven otherwise . In menopause, you still have some estrogen although it's reduced compared to its premenopausal levels. The source of postmenopausal estrogen is the adrenal zona reticularis where DHEA is produced and then aromatized in ovarian stroma and fatty tissues to Estrone. It's the effect of unopposed estrone (as no more progesterone from corpus letuem) that causes endometrial hyperplasia which is a precursor of endometrial carcinoma, the most common female genital cancer in the aging US population and the second killer after ovarian cancer.

Sudden Severe Headache A patient that developed a sudden severe headache described as the most severe headache of his life This is sub-arachnoid hemorrhage in most USMLE questions

Female with breast lump Although of course there are many differentiating points among the causes but Age is often a big player in USMLE Questions less than 35, think Fibroadenoma more than 35, think either cancer or fibrocystic disease of the breast

Old man with lower back pain Old man with lower back pain and osteoblastic lesions in the lumbar spine is metastatic prostatic carcinoma until proven otherwise

Leukemia + Spherocytes A leukemic patient with spherocytes in blood smear Think CLL as it's associated with Autoimmune hemolytic anemia in some patients

Great improvement after splenectomy Whenever you see a case describing a child that has seen tremendous improvement of his anemia after splenectomy think Spherocytosis don't think other hemolytic anemias or hemoglobinopathies, true they improve with spleen removal but not as classical as in the case of congenital spherocytosis Diarrhea Transmural inflammation diarrhea transmural inflammation = Crohn's Disease

Jaundice Cataract after birth Small infant Jaundice Cataract

Vomiting Hepatomegaly Reducing sugars in urine Dx Galactosemia Enzyme: Galactose 1-P Uridyltransferase Treatment: Stop Galactose and Lactose

Dexamethasone Suppression Test -Whenever you see a case with positive DST to high dose then pick the option of doing brain CT [because it's most likely cushing disease ie pituitary adenoma] -Whenver you see a case with negative DST to high dose then pick the option of doing lungs or abdomen CT or U/S because it's most likely ectopic ACTH source such as lung CA or Adrenal adenoma