Infectious Disease Pathology p76-89

SPECIAL SILVER STAINS: • Warthin Starry, Dieterle • Treponema pallidum • Legionella • Bartonella

DIRECT FLUORESCENT ANTIBODY STAIN • Sputum or respiratory washings • Legionella, Bordetella persussis, Herpes virus and others • High specificity/Low sensitivity

For very very small organisms – to see, must coat w/silver.

The one we do most often is for influenza and parainfluenza

Dieterle/Warthin-Starry Stain:

Fluorescent antibody stain: Herpes-infected cells Highly specific but lack sensitivity. If you do DFA test and it’s positive, that’s really good. Example: B. pertussis (whooping cough) DFA on sputum – specificity is 99%, sensitivity is only 30%

Shows Treponema pallidum (syphilis)

Bronchopneumonia: • Patchy or “hit and miss” • Staphylococcus, GNRs, anaerobes • Aspiration with spread through the airways Bronchopneumonia:

Patchy bronchopneumonia:

* = Pneumonia. Bronchopneumonia – hit-and-miss – spreading through the airways. ANY ORGANISM can cause bronchopneumonia, anything can spread through the airways – usually think of staphylococci, streptococci, GNRs. Lobar pneumonia: • Involvement of the entire lobe (most of it) • The difference is that only a limited # of organisms cause it – Streptococcus pneumoniae, Klebsiella pneumoniae, Haemophilus influenzae • Encapsulated bacteria • Aspiration then spread through alveolar walls (pores of Kohn)

Spread through pores of Kohn – get complete involvement of a lobe.

Paragonimus westermani: • Human lung fluke • Granulomatous reaction to the eggs • If you see eggs in lung w/flat operculum = paragonimus

Aspergillus fumigatus (A. flavus): • Opportunistic infection in transplant and hematology/oncology patients • More often, patients w/severe neutropenia • Narrow, septate hyphae that branch at acute angles (45 degrees or less) Invasion of arterial wall by Aspergillus (PAS):

Narrow hyphae, crosswalls, dichotomous branching.

Aspergillus and Mucor both involve vascular invasion, but we usually associate it more w/Aspergillus.

Mucormycosis (Rhizipomycosis):: • Mucor and Rhizopus • Diabetic ketoacidosis (DKA), transplant/heme-onc • Nasal sinuses, lung, GI tract, brain • Rhinocerebral mucormycosis – (spread from nasal  brain) • Morphologic identification or culture • Broad irregular ribbon-like hyphae, no septae (aseptate/coenocytic), right-angle branching • Aseptate fungal hyphae (no crosswalls) • Branch at 90 degrees (right angles) • Diabetics (poorly controlled) and transplantation patients

Rhinocerebral mucormycosis:

Mucor species in a lung biopsy (aseptate hyphae):

Above (left): Cloudy nasal sinus, filled w/organisms and inflammatory cells. Treatment is ALWAYS SURGERY debridement. Above (right): H&E stain – very broad, very irregular, no crosswalls. Can see right angle branches in some spots.

Above (left): Mucormycosis in a blood vessel – very irregular fragments of the organism. Above (right): Filamentous fungi – cut like a pipe (cross-section). Don’t confuse w/yeast!

Actinomycosis: • Sulfur granules (yellow on gross) • Sulfur granules (pink/blue on H&E) • Filamentous anaerobic bacteria • Gram-positive, acid-fast- negative filamentous bacteria (Actinomyces) • Aspiration • Draining fistulas are common • People w/poor oral hygiene • Non acid-fast anaerobe. Nocardia is AEROBE, WEAKLY ACID-FAST. Both filamentous, both G+ Gram-positive, filamentous Actinomyces  2000x – sulfur granules – can see blue filatmentous organisms.

Colonies of Actinomyces:

Yellow sulfur granules Fistula extending out of neck of patient

Colony of Actinomyces in a bronchiole: Actinomyces colonies on H&E Stain:

H&E Stain

Have orange-pinkish rim around them. Background cells are neutrophils.

Salpingitis: Inflammation/infection of the fallopian tube. • Chlamydia trachomatis • Neisseria gonorrhoeae • Sterility, ectopic pregnancy Cervicitis, urethritis, PID (w/inflammation of fallopian tube). More common w/G (because more virulent) – can also give you other things (sepsis, skin rashes, joint infections) bc it can survive outside cells. C is an obligate intracellular pathogen.  Pus in the finger-like projections (fimbriae).

Above: Salpingitis. Pus in the lumen.

Abscess w/segmented neutrophils:

Above (left): Staph is known for causing abscesses in the body – look for half-full circles (solid on bottom, black on top) = air-fluid level. Above (middle): Brain abscess – if it lasts a long time, can get fibrosed around the edges. Anaerobic organisms are most common in brain abscesses. Above (right): Abscess with mostly segmented neutrophils

Appendicitis: • Neutrophils are easiest to see in the muscle and fat • Leukemoid reaction (left shift) is common – high granulocyte count. • Pyuria due to involvement of the ureter Neutrophils:

Pyelonephritis: • Most are ascending (post bladder infection) • E. coli is most common cause • High fever, chills , pain • “Thyroidization of the kidney” seen on H&E-stained sections – lots of lymphocytes, protein in the tubules. Two kinds: most common is ascending (bladder infection  travel up ureter to kidney) Descending – comes through blood, usually in someone w/endocarditis. If bacteria growing on heart valves, can flip off and make their way down to the glomeruli, where they cause pyelonephritis (usually staph or strep). Thyroidization:

Lymphocytes that look like C cells (parafollicular cells) Tubules filled w/protein that look like follicles

Can look around, find a glomeruli

Diphtheria: • Corynebacterium diphtheriae – infection in upper airway. Often in pharynx but sometimes deeper down. • C. diphtheriae can be normal flora- do toxin assay for diagnosis of diphtheria • Exotoxin destroys myocytes  myocarditis  can cause a fatal arrythmia  heart failure • Abscesses in the myocardium Pseudomembrane:

Pseudomembrane:

Pseudomembrane rarely does any damage to the patient except producing the toxin  distant sites. Above (right): Two-part toxin-exotoxin that causes the damage

Syphilis: • Obliterative endarteritis seen in primary, secondary and tertiary syphilis – inflammation and destruction of the arteries • Plasma cells surround vasa vasorum • Tertiary- ascending or thoracic aorta is most commonly involved (80%) • Treponema pallidum Chancre on Chest 

Primary – chancre Secondary – rash + condyloma lata Tertiary – organism can go to any site in the body. Most often – thoracic aorta (ascending) – aneurysm (bubbling) Aneurysm in ascending aorta:

Inflammation in aorta wall:

Plasma cells in the wall.

Silver stain:

Destruction of elastic tissue.

Tuberculosis: • Mycobacterium tuberculosis • Communicable – person-to-person • Necrotizing granulomas (microscopic) is usual but non-necrotizing granulomas are possible • Caseous necrosis (gross) • Ghon complex in lung (primary TB) – peripheral lesion and central lymph node lesion • Apical disease (secondary/reactivation TB) Necrotizing granuloma:

Granulomas w/necrosis, histiocytes, giant cells, lymphocytes at the periphery.

* Large granulomas (hilar lymph nodes) ** Small granulomas (miliary TB) Lymphadenopathy – esp. in hilar/central part of lung

Hilar lymphadenopathy (hilus – central part of lung where major vessels/airways enter). Can see this in histo or in TB. Small granulomas everywhere – miliary TB (organism erodes into pulmonary artery  shower entire lung). Ghon Complex or Primary Complex: TB in the upper lobecaseous granulomas Apical involvement = reactivation TB. More oxygen there. Secondary TB is more aggressive – aggression is immune system reacting to organism: more necrosis, cavitation, lymph node proliferation. Ghon Complex: LN and peripheral lesion. Peripheral lesion in mid-lung fields, some of the organisms travel through lymphatics to hilar lymph nodes.

Histoplasma capsulatum: • Not communicable • Necrotizing granulomas • Small (2-3 microns), budding yeast • Intracellular H&E Stain with yeasts of H. capsulatum:

Hard to see yeast.

Giemsa stain:

Sample from blood.

GMS (Silver) stain:

Yeasts inside macrophages – pneumocystis is NEVER intracellular

Coccidioides immitis– sometimes referred to as “Valley Fever” • California and Arizona • Necrotizing granulomas • Spherules contain endospores C. immitis Spherules – H&E:

GMS (silver) Stain of C. immitis:

PAS Stain of Coccidioides immitis:

Spherules are BIG. Compare to surrounding inflammatory cells. Endospores are as big as neutrophils.

Blastomyces dermatitidis: • Large yeast with Broad-Based Buds • Pseudoepitheliomatous hyperplasia mimics (clinically and microscopically) squamous carcinoma in skin and in the larynx – epithelium proliferates, piles up, looks like cancer • Inflammation is mixed: histiocytes with giant cells and abscesses with neutrophils • ALWAYS starts out as pulmonary infection – then is more likely to spread to skin and larynx (lesions look like cancer) Pseudoepitheliomatous hyperplasia H&E shows broad-based-budding:

GMS (silver) Stain:

Middle figure: Lung. See budding yeast. Not crypto because it has a double ring around it. Cytoplasm shrinks away from cell wall – is not encapsulated.

Pneumocystis pneumonia: • (Pneumocystis carinii pneumonia) or PCP • Pneumocystis jiroveci • Two forms: cysts and trophozoites • Cysts on GMS stain • Trophozoites on Giemsa stain Pneumocystis pneumonia on H&E Stain  Alveolar space filled w/bubbly stuff (organisms) .

Giemsa Stain of BAL:

Cysts Silver stain – see tea cups.

Trophozoites

Pneumocystis cyst w/ 8 trophozoites.

GMS stain:

Cysts (“cups, targets, grooves”) No budding, not inside cells – just inside alveolar space.

Cryptococcus neoformans: • Variably-sized budding yeast with thick capsule of mucopolysaccharides • India Ink stain (poor sensitivity and specificity) • Latex agglutination on CSF or serum has high sensitivity and specificity • Cryptococcal meningitis 100% fatal if untreated Similar size to blastomyces, but has very thick capsule. C. Neoformans in glomeruli (H&E):

C. neoformans (GMS):

Mucin stain:

Above (middle): Big capsule, huge size variation. Can be as small as histo, as big as blasto. Narrow-based bud. Above (right): Mucin stain – can see capsule of Cryptococcus neoformans. Assume if encapsulated yeast, mucin+ = cryptococcus.

GMS Stain- C. neoformans

India Ink: C. neoformans (latex agglutination +):

Chest wall biopsy. Capsule lots of space.

C. Neoformans in CSF

Lots of space surrounding – do not see a second ring (like blasto, which did not have a true capsule) Polio: • Anterior/motor horns have receptors • Paralytic polio occurs in non-vaccinated adults if infected by the virus Polio: Anterior horns are destroyed. Best seen on low power  Young children/babies usually don’t have receptors on their motor horns for the virus – so if exposed when very young  get an enteritis, get immune, do not get paralytic polio. If you exposed for the first time when you’re older and not immune  paralysis.

Entameba histolytica: • Flask-shaped ulcers in the colon • Erythrophagocytosis- amoebae ingest RBCs; if so, it is E. histolytica H&E- Flask-shaped ulcer of E. histolytica:

Erythrophagocytosis:  Can find ameobae containing RBCs – erythrophagocytosis.

E. histolytica – see erythrophagocytosis

Causes of diarrhea: INVASIVE: Salmonella and Shigella Campylobacter Many E. coli Entamoeba C. difficile

NON-INVASIVE: Vibrio Cryptosporiudium Giardia

If you see RBCs and WBCs in stool, means that the organism is invasive and destroying mucosa. Vibrio – makes toxin (that’s what does the damage) but doesn’t invade. Cryptosporidium and Giardia – coat the intestine but don’t invade, so don’t see RBCs and WBCs.

INVASIVE = SEE RBCs, WBCs IN STOOL.

Strongyloidiasis: • Autoinfection- the entire life cycle can occur in humans if they are immune compromised • Association with HTLV-1 infections Worm that goes through entire life cycle in the body, resulting in huge numbers of organisms. Will invade lung and cause pneumonia because, as it travels through the lung and poops, it poops out bacteria that cause pneumonia. H&E Stain of Strongyloides (calcified worm) 

Adenovirus: • Nucleus only inclusions • Cowdry B type in Adenovirus • Cowdry A type in Herpes H&E Stain with Adenovirus inclusions in hepatocyte nuclei 

CMV: • •

Enlarged cells Intranuclear (Cowdry B) and cytoplasmic inclusions are present in some cells

Below: Arrows = CMV-infected cells

CMV infection in lung:

Owl’s eyes in intestines.

Toxoplasmosis: • Brain abscess • “Ring-enhancing” lesions • Cysts

Toxoplasmosis: Cysts in brain (abscesses) 

H&E Stain of brain biopsy with Toxoplasma:

Cysts of T. gondii in brain- H&E Stain:

Encysted forms w/bradyzoites. If causing active infection in the lung/other sites, will see tachyzoites that look like bananas.

Hepatitis: • Lymphocytes in the portal zones • Loss of hepatocytes • Cirrhosis Chronic Hepatitis: Hepatocytes w/inflammatory cells.

Chronic Hepatitis: Plasma cells, lymphocytes.

Get lots of lymphocytes (viral infection) – inflammation around the bile ducts/artery/vein.

Leftover Infectious Disease Test Q’s: Couldn’t find a good place for these in the notes – some are review from Micro. Test q: Petechiae of skin, progressing to necrosis of finger tips, nose and ear lobes, suggests infection by: Meningococci. Test q: Which of the following poses the lowest risk for person-to-person spread to physicians, nurses, or laboratorians? Anthrax (Other choices: Smallpox, Plague, Viral hemorrhagic fever) Test q: A 22F suffers a tick bite on a hike in southern Indiana. She develops fever w/a total-body rash that includes palms of her hands. Biopsy of the rash shows thrombosed blood vessels. Swollen endothelial cells contain tiny “dots” on Giemsa stains. Diagnosis? Rickettsia rickettsii. Test q: A 32M professional football player (not a quarterback) presents with a history of spider bite on his back. The site is now ulcerated, painful, and erythematous. The patient has fever of 102F. You would expect a Gram stain of the tissue to show: Gram-positive cocci in clusters. Test q: A 56M presents w/ulcers and mucocutaneous lesions around his nose and mouth after a trip to South America. A skin biopsy shows ameboid microorganisms and mixed inflammation. Erythrophagocytosis is not present. Gram stain and GMS (silver) stains show no microorganisms. Diagnosis? Balamuthia mandrillaris.

All Other Test Q’s: Review questions from years past: Test q: On a routine visit to the physician, an otherwise healthy 51y/o man has a BP of 150/95mmHg. If the patient’s hypertension remains untreated for years, which of the following cellular alterations will most likely be seen in the myocardium? Hypertrophy. REPEATED x3 Test q: As the human female ages and gives birth to children, the endocervical epithelium changes from columnar to squamous. This change is called: Metaplasia. Test q: A long-time male cigarette smoker exhibits replacement of bronchial glandular mucosa by benign squamous cells. This change is called: Metaplasia. Test q: Mature squamous epithelium in bronchial lining is an example of: Metaplasia Test q: The “apple core” appearance of colon cancer on x-rays and inversion of the nipple in breast cancer are both due to: Desmoplasia. Test q: A 72y/o woman is admitted to the hospital in an obtunded condition. Her temp is 37*C, pulse is 95/min, respirations are 22/min, and BP is 90/60mmHg. She seems to be dehydrated and has poor skin turgor. Her serum glucose level is 872 mg/dl. Urinalysis shows 4+ glucosuria, but no ketones, protein, or blood. Which of the following factors is most important in the pathogenesis of this patient’s condition? Insulin resistance (Other choices were: HLA- DR3/HLA-DR4 genotype, Autoimmune insulitis, Severe depletion of β cells in islets, Virus-induced injury to β cells in islets.) Test q: A child is born w/a single functional copy of a tumor suppressor gene. At the age of 5, the remaining normal allele is lost through mutation. As a result, the ability to control the transition from G1 to S phase in the cell cycle is lost. Which of the following neoplasms is most likely to occur? Retinoblastoma Test q: The following tumors are known for being invasive but generally NOT metastatic: Glioblastoma multiforme and basal cell carcinoma. Test q: The nuclear proteins Rb and p53 are gene products for: Tumor suppressor genes. Test q: A 40y/o woman who was recently in an automobile accident noticed a firm mass in the upper-outer quadrant of her right breast. A mammogram 2mo ago was normal. Which microscopic description is most consistent w/the clinical history? Giant cells and foamy macrophages. Test q: The most important property of a tumor that determines malignant potential is: Metastasis. Test q: A 69y/o man has had difficulty w/urination for the past 5 years. A digital rectal exam reveals that the prostate gland is palpably enlarged to about twice normal size. A transurethral resection of the prostate is performed, and the microscopic appearance of the prostate “chips” obtained is that of large glands lined by 2 cell layers and with intervening stroma. Which of the following pathologic processes has most likely occurred in the prostate? Hyperplasia. Test q: Angiogenesis in tumor cells is stimulated by: VEGF. Test q: Degradation of ECM Type IV collagen in metastasis is due to the action of: Metalloproteinases. Test q: A 26F has a lump in the left breast. On phys exam by the physician, there is an irregular, firm, 2cm mass in the upper inner quadrant of the breast. No axillary adenopathy is noted. A fine-needle aspirate of the mass shows carcinoma. The patient’s 30y/o sister was recently diagnosed w/ovarian cancer, and 3 years ago, her maternal aunt was diagnosed w/ductal carcinoma of the breast and had a mastectomy. Which of the following genes is most likely to have undergone mutation to produce these findings? BRCA1 (DNA repair gene). Test q: A 40M has been taking daily insulin injections for the past 25 years. When he does not arrive at work, a friend visits his house and finds him on the floor in an obtunded state. He is taken to the hospital by ambulance. On admission to the hospital, he cannot be aroused. He is afebrile, with a pulse of 90/min, resp 17/min, and BP 90/60 mmHg. Lab studies show a Hbg A1c concentration of 8.9%, serum glucose level of 11 mg/dL, and serum osmolality of 295 mOsm/kg. Urinalysis shows 4+ ketonuria w/a specific gravity of 1.010. Which of the following statements best characterizes these findings? He is in poor glycemic control and has had an insulin overdose. (Other choices: He is in good glycemic control but has developed ketoacidosis; He is in poor glycemic control and is not taking his insulin; He is in good glycemic control but has not eaten food recently; He is in poor glycemic control and has developed a hyperosmolar coma.) Test q: A 23F receiving corticosteroid therapy for an autoimmune disease has an abscess on her upper outer right arm. She undergoes minor surgery to incise and drain the abscess, but the wound heals poorly over the next month. Which of the following aspects of wound healing is most likely to be deficient in this patient? Collagen deposition. (Other choices: Re-epithelization; Fibroblast growth factor elaboration; Serine proteinase production; Neutrophil infiltration) Test q: Which of the following are labile cells? Gastric columnar epithelial cells. (Other choices: Cardiac muscle fibers, Hepatocytes, Fibroblasts, Smooth muscle cells) Test q: The most common paraneoplastic syndrome is: Hypercalcemia. Test q: Which best characterizes a post-mortem clot? Chicken fat appearance. Test q: In an experiment, peripheral blood T lymphocytes are collected and placed in a medium that preserves their function. The lymphocytes are activated by contact w/antigen and incubated for several hours. The supernatant fluid is collected and is found to contain a substance that is a major stimulator of monocytes and macrophages. Which of the following substances is most likely to stimulate these cells? Interferon-γ. Test q: At autopsy, a patient’s liver shows marked stasis of blood in the central veins. Lung shows congestion of capillaries and pink, acellular material in the alveoli. What is the most likely cause of these findings? Left heart failure. Test q: A 50y/o woman saw her physician after noticing a mass in the right breast. Physical exam showed a 2cm mass fixed to the underlying tissues

and three firm, nontender, lymph nodes palpable in the right axilla. There was no family history of cancer. An excisional breast biopsy was performed, and microscopic exam showed a well-differentiated ductal carcinoma. Over the next 6mo, additional lymph nodes became enlarged, and CT scans showed nodules in the lung, liver and brain. The patient died 9mo after diagnosis. Which of the following molecular abnormalities is most likely to be found in this setting? Amplification of the ERBB2 (HER2) gene in breast cancer cells Test q: A 68F suddenly lost consciousness and, on awakening 1 hour later, she could not speak or move her right arm and leg. Two months later, a head CT scan showed a large cystic area in the left parietal lobe. Which of the following pathologic processes has most likely occurred in the brain? Liquefactive necrosis. REPEATED x2 Test q: A 30y/o woman sustained a traumatic blow to her right breast. Initially, there was a 3cm contusion that resolved within 3wk, but she then felt a firm lump that persisted below the site of the bruise 1mo later. What is the most likely diagnosis for this lump? Fat necrosis Test q: A 61y/o woman has felt a lump in her breast for the past 2mo. On phys exam, there is a firm 2cm mass in the right breast. An excisional biopsy specimen of the mass shows carcinoma. Immunoperoxidase stains for matrix metalloproteinase-9 are performed on the microscopic tissue section and show pronounced cytoplasmic staining in the tumor cells. Which of the following characteristics is most likely to be predicted by this marker? Invasiveness. Test q: A property of the initiator family of carcinogens is: Chemicals that damage genes. Test q: Direct acting carcinogens are: Weak carcinogens. Test q: A 44F has a right breast mass. Grossly, multiple blue-dome cysts are present. These gross changes suggest: Fibrocystic disease. Test q: Which of the following histologic features seen in breast biopsies place the patient at increased risk for ductal carcinoma? Ductal papillomatosis. Test q: A 45F receives 4wk treatment for mastitis of the right breast. Biopsy shows invasive carcinoma w/lymphatic invasion. Initial therapy in this case is: Chemotherapy. Test q: Which of the following breast carcinomas has the poorest prognosis? Metaplastic carcinoma. (Other choices: Tubular carcinoma, Mucinous carcinoma, Medullary carcinoma, Adenoid cystic carcinoma) Test q: A breast biopsy shows Indian-file growth pattern of the tumor cells. In other areas, a targetoid growth pattern is seen. Diagnosis: Lobular carcinoma. Test q: A 50M long-time smoker has a biopsy of a right central lung mass. The right mainstem bronchus is not obstructed. The tumor shows high nucleus-to-cytoplasm ratio and nuclear molding. Neither squamous nor glandular differentiation are present. Treatment of the patient would include: Chemotherapy. Test q: The left breast of a 39y/o female is slightly enlarged compared w/the right. The skin overlying this breast is thickened, reddish-orange, and pitted. Mammography reveals a 3cm underlying density. A fine-needle aspirate of this mass reveals carcinoma. How is the gross appearance of the left breast best explained? Lymphatic obstruction. Test q: A 50M experienced an episode of chest pain 6hr before his death. A histologic section of left ventricular myocardium taken at autopsy showed a deeply eosinophilic-staining area w/loss of nuclei and cross-striations in myocardial fibers. There was no hemorrhage or inflammation. Which of the following conditions most likely produced these myocardial changes? Coronary artery thrombosis. Test q: Which of the following is associated w/hereditary nonpolyposis colon cancer (HNPCC)? Inability of DNA mismatch repair genes (mutation) to correctly repair damaged DNA. Test q: A 48y/o woman notices a lump in her left breast. On phys exam, the physician palpates a firm, non-movable, 2cm mass in the upper outer quadrant of the left breast. There are enlarged, firm, nontender lymph nodes in the left axilla. A fine-needle aspiration biopsy is performed, and the cells present are consistent w/carcinoma. A mastectomy w/axillary lymph node dissection is performed, and carcinoma is present in two of eight axillary nodes. Which of the following factors is most likely responsible for the lymph node metastases? Increased laminin receptors on tumor cells Test q: An epidemiologic study investigates the potential cellular molecular alterations that may contribute to the development of cancer in a population. Data analyzed from resected colonic lesions show that changes are occurring that demonstrate the evolution of a sporadic colonic adenoma into an invasive carcinoma. Which of the following best describes the mechanism producing these changes? Malignant transformation involves accumulation of mutations in protooncogenes and tumor suppressor genes in a step-wise fashion. Test q: A 70y/o woman reported a 4mo history of a 4kg weight loss and increasing generalized icterus. On phys exam, she is afebrile, and her blood pressure is 130/80mmHg. An abdominal CT shows a 5cm mass in the head of the pancreas. Fine-needle aspiration of the mass is performed. On molecular analysis, the neoplastic cells from the mass show continued activation of cytoplasmic kinases. Which of the following oncogenes is most likely to be involved in this process? RAS Test q: Prevention of lethal squamous cell carcinoma in patients suffering from xeroderma pigmentosa requires: Avoiding sunlight, Test q: A 67M developed increasing shortness of breath over a three day period. His neighbor drove him to the ED where a CXR revealed fluffy pulmonary infiltrates, a partially calcified, rounded density in the right upper lobe, and bilateral pleural effusions. Aspiration of some of the pleural fluid showed a specific gravity of 1.006. Of the following the effusion is most likely due to: Congestive heart failure. (Other choices: Lung cancer, Pneumonia w/pleural involvement, Rupture of the thoracic duct into the pleural cavity, and Tuberculosis w/pleural involvement) Test q: Spontaneous venous thrombosis and migratory thrombophlebitis are most characteristic of: Adenocarcinoma of the pancreas. (Other choices: Chronic cholecystitis; Acute hemorrhagic pancreatitis; Islet cell tumor; Parathyroid hyperplasia) Test q: A 79F, previously healthy, feels a lump in her right breast. The physician palpates a 2cm firm mass in the upper outer quadrant. Nontender

right axillary lymphadenopathy is present. A lumpectomy w/axillary lymph node dissection is performed. Microscopic exam shows that the mass is an infiltrating ductal carcinoma. Two of 10 axillary nodes contain metastases. Flow cytometry on the carcinoma cells shows a small aneuploid peak and high S-phase. Immunohistochemical tests show that the tumor cells are positive for estrogen receptor, negative for ERBB2 (HER2/neu) expression, and positive for cathepsin D expression. Which of the following is the most important prognostic factor for this patient? Presence of lymph node metastases. Test q: A patient presents to the ER w/jaundice. Routine lab studies show that both the total and direct bilirubin are elevated, the alk phosphatase is 6x the upper limit of normal, and both the ALT and AST are within the reference ranges for these enzymes. These results would be most consistent with: Obstructive jaundice. Test q: Which of the following malignant tumors most commonly metastasizes to the liver? Adenocarcinoma of the colon (Other choices: Renal cell carcinoma, Prostate adenocarcinoma, Glioblastoma multiforme [Astrocytoma grade IV], Osteosarcoma) Test q: The best initial lab test to order if you are evaluating a patient for autoimmune disease is: Antinuclear antibody (ANA). Test q: A 45F presents w/a painful, swollen left breast. Peau d’orange is present, the nipple is retracted, and the skin is dimpled. These changes are consistent with: Inflammatory carcinoma. Test q: All of the following increase risk for breast cancer in women EXCEPT: Oral contraceptives (Other choices: Obesity, Atypical hyperplasia, BRCA1, BRCA2) Test q: All of the following are seen in fibrocystic disease of the breast EXCEPT: Cribriforming. (Other choices: Microcalcification, Cystic change, Apocrine change, Epithelial hyperplasia)

Nutrition section from years past: An epidemiologic study observes increased numbers of respiratory tract infections among children living in a community in which most families are at the poverty level. The infectious agents include Streptococcus pneumoniae, Haemophilus influenzae, and Klebsiella pneumoniae. Most of the children have had pneumonitis and rubeola infection. The study documents increased rates of keratomalacia, urinary tract calculi, and generalized papular dermatosis in these children. A deficiency of which of the following vitamins is most likely to be present in these children? Vitamin A. REPEATED x2 A 3y/o child has had a succession of respiratory infections during the past 6 months. On phys exam, the child appears chronically ill, listless, and underdeveloped. He is 50% of ideal body weight and has marked muscle wasting. Lab findings include Hgb of 9.4 g/dL, hematocrit 27.9%, MCV 3 3 3 75µm , platelet count 182,000/mm , WBC count 6730/mm , serum albumin 4.1 g/dL, total protein 6.8g/dL, glucose 52 mg/dL, and creatinine 0.3 mg/dL. Which of the following conditions is most likely to explain these findings? Marasmus. Children suffering from Kwashiorkor often fail to recover when proper nutrition is returned to their diet due to: intestinal atrophy. The malnutrition seen in severe burn patients is similar to that seen in: Kwashiorkor. Which vitamin supplement can be used to lower LDL and Triglycerides and increase HDL? Niacin. Over the past year, a 55F has had worsening problems w/memory and the ability to carry out tasks of daily living. She has had watery diarrhea for the past 3mo. Phys exam shows red, scaling skin in sun-exposed areas. The deep tendon reflexes are normal, and sensation is intact. Which of the following is the most likely diagnosis? Pellagra.