Pathoma Ch 6, 10, 14, 18 (WBC, GI, Male GU, MSK) Flashcards
6. WBC D/o 10. GI path 14. Male GU 18. MSK
1
Q
ALL vs. AML
(a) Cell marker
(b) Age on onset
A
ALL vs. AML- both acute leukemias (so blasts over 20% of bone marrow), but of the two different hematopoietic lineages
ALL = acute lymphoblastic leukemia
(a) tdt positive = DNA polymerase found only in lymphoblasts (not in myeloid blasts or mature lymphocytes)
(b) Children
AML = acute myeloid leukemia
(a) MPO (enzyme used in O2 dependent killing to catalyze H2O2 –> HOCl, so makes sense it would be seen in neutrophils and macrophage lineage)
- cystal aggregates of MPO = Auer rods
(b) Adults, like over 65
2
Q
Gastroschisis vs. omphalocele
A
Gastrochisis = failure for anterior abdominal wall to properly fuse fully => abdominal contents herniate out, not surrounded by peritoneum
Omphalocele = persistent herniation of bowel into umbilical cord => failure of bowel to return during 90 degree rotation
-associated w/ cardiac complications
3
Q
How to differentiate follicular lymphoma from follicular hyplerplasia (as a result of RA or early HIV)
(a) Tingible body macrophages
(b) Architecture of LN
A
Follicular lymphoma (neoplastic prolif) vs. follicular hyperplasia (hyperplastic prolif)
(a) Tingible body macrophages are eating up dead cells- won’t be seen in Follicular lymphoma b/c apoptosis is inhibited
(b) LN architecture in maintained in follicular hyplerplasia (follicles all on the periphery, just more of them and they’re bigger), while in follicular lymphoma the follicles take over the entire lymph node (into the cortex) and normal architecture of LN is not maintained
4
Q
(a) Triad of Behcet syndrome
(b) Mechanism of disease
A
(b) Behcet syndrome = autoimmune vasculitis (immune complex inflammation of small vessels)
(a) Oculo-oro-genital syndrome
- recurrent apthous ulcers (canker sores), genital ulcers, and uveitis
5
Q
CLL vs. Hairy Cell Leukemia
(a) Cell of origin
(b) Classic molecular marker or stain
A
Both are neoplastic proliferation of B cells
CLL
(a) Neoplastic proliferation of naive B cells
(b) CD5 and CD10 posiitve
Hairy Cell Leukemia
(a) Neoplastic proliferation of mature B cells
(b) TRAP stain positive
6
Q
Differentiate acute and chronic leukemia
A
Acute leukemia = neoplastic proliferation of immature cells of the myeloid or lymphoid lineage
Chronic leukemia = neoplastic proliferation of mature circulating lymphocytes
7
Q
MC form of Non Hodgkin Lymphoma
(a) Growth pattern
(b) Differentiation
A
DLBCL = diffuse large B cell lymphoma
(a) Grows diffusely in sheets
(b) Aggressive cancer b/c it’s poorly differentiated, larger the cell the less they are like the normal cell (so more poorly differentiated they are)
8
Q
Name 3 complications of myeloproliferative disorders
A
Myeloproliferative disorders = neoplastic accumulation of mature cells of the myeloid lineage
3 complications
- transformation to AML
- bone marrow fibrosis
- increased risk of hyperuricemia and gout
- 2/2 increased DNA turnover
9
Q
Differentiate leukoplakia and hairy leukoplakia
A
Leukoplakia = white plaque that can’t be scared off (so not candida), pre-malignant lesion to squamous cell carcinoma of the mouth
Hairy leukoplakia = rough white patch on LATERAL tongue (lateral is key) in immunocompromised pts, 2/2 EBV infection
-EBV-induced squamous cell hyperplasia, NOT pre-malignant
10
Q
2 tests to confirm H. pylori eradication
A
- Negative urea breath test
- b/c H. pylori produced urease (and proteases), so urea will be present in breath - lack of stool antigen
11
Q
CML
(a) Protein responsible
(b) Tx
(c) Transformation to which acute leukemia?
(d) Key CBC finding
A
CML = chronic myeloid leukemia
(a) t(9,22) makes BCl-ABL fusion protein that is a constitutively active tyrosine kinase
(b) Tx = Imatinib to block tyrosine kinase activity
(c) If CML transforms to acute leukemia: 2/3 AML and 1/3 ALL
- key here that it’s not only AML!!!! b/c the mutation is in the hematopoietic stem cell, not the myeloid stem cell
(d) Leukocytosis specifically w/ basophilia
12
Q
MC location for carcinoid tumor
A
Small bowel
13
Q
MC subtype of Hodgkin Lymphoma
A
Nodular sclersois Hodgkin lymphoma (NSHL): LN divided by broad bands of fibrosis w/ Reed Sternberg cells in open spaces = Lacunar cells
14
Q
Presentation of mumps infection
(a) Feared complication in teenagers
A
Mumps p/w b/l inflammed parotid glands
(a) Teenagers w/ mumps can develop orchitis that carries risk of sterility
15
Q
Which myeloproliferative d/o has the lowest risk of hyperuricemia/gout?
A
Essential thrombocytopenia has the lowest risk of hyperuricemia/gout b/c the high turnover is of plts (no nuclear material), not of RBCs or granulocytes as seen in P. Vera and CML
16
Q
When do carcinoid tumors cause carcinoid syndrome?
A
Only can cause carcinoid syndrome (bronchospasm, diarrhea, flushing from excess 5-HT) when the tumor’s drainage bypass the portal vein
So once the tumor mets to the liver and is drained by the hepatic vein, then 5-HT won’t be degraded into 5-HIAA by MAO in the liver (then 5-HIAA excreted in urine)
17
Q
Pt w/ long standing celiac disease and very tight/adherent diet control presents w/ recurrent disease
Concern?
A
Late complications of celiac disease:
- small bowel carcinoma
- T-cell lymphoma
Key here is that Celiac disease is T-cell mediated, so causes rare lymphoma that is T-cell (almost all lymphomas are B cell!!)
These two late complications present as refractory disease despite good dietary control
18
Q
Chronic autoimmune gastritis vs. H. pylori gastritis
(a) Risk of which malignancies?
(b) Location
A
(a) Both cause incrase risk of gastric adenocarcinoma (intestinal type) b/c chronic inflammation causes metaplasia to intestinal cells
- then H. pylori also increases risk of MALT lymphoma
(b) AI gastritis damages parietal cells which are concentrated in the body and fundus of the stomach. While H. pylori manifests MC w/ inflammation of the antrum
19
Q
Quick way to differentiate Mallory-Weiss syndrome from esophageal varices
A
Both will cause hematemesis, but Mallory-Weiss hematemesis is painful (b/c it’s a tear in the mucosa), while esophageal varices are painless bc/ veins have already ruptured
20
Q
MC genetic translocation seen in leukemias
(a) B-ALL
(b) Acute promyelocytic leukemia
(c) CML
A
MC genetic translocation seen in
(a) B-ALL = t(12,21)
- 21: hence association w/ Down syndrome
(b) APL: t(15,17) that disrupts retinoic acid receptor needed for promyelocytic maturation
(c) CML: t(9,22) = Philadelphia chromosome
21
Q
What two areas need prophylactic chemotherapy in tx of B-ALL?
A
B-ALL has a very good prognosis, w/ an excellent response to chemo
-but the chemo can’t cross the BBB or the blood-testes barrier => CSF and scrotum need prophylactic chemo
22
Q
Pathology behind achalasia
(a) Secondary infectious cause of achalasia
A
Achalasia is 2/2 damage to ganglion cells in the myenteric plexus, myenteric plexus located btwn the inner circular and outer longitudinal layers of the muscularis propria
(a) Mostly idiopathic, but achalasia can be 2/2 chagas disease (trypanosoma cruzi infxn)
23
Q
How to differentiate the two types of ALL
A
ALL split into B-ALL and T-ALL, differentiate by cell markers
-but both tdt + (DNA polymerase in lymphoblasts)
B-ALL: CD10, CD19, CD30
T-ALL: CD2 to CD8 (no CD10)
24
Q
What is Whipple disease?
(a) Cause
(b) Clinical presentation
(c) Systemic features
A
(a) Whipple disease = infection w/ Tropheryma whippelli organism- organism can’t be fully destroyed by macrophages => macrophages accumulate partially-destroyed organisms inside lysosomes and build up in the lamina propria (CT) of the gut
(b) Small bowel lamina propria (positive on PAS stain for organism) is inundated w/ macrophages, which block lacteals => chylomicrons can’t be absorbed => pts p/w fat malabsorption and steatorrhea
(c) Can also cause systemic tissue damage: arthritis, cardiac valves, LN, CNS
25
Differentiate the two subsets of lymphoma: NHL vs. HL
(a) MC?
(b) Creation of mass
Non Hodgkin Lymphoma vs. Hodgkin Lymphoma
(a) NHL 60%, HL only 40%
(b) NHL- the mass is all proliferated cells
While in HL rare neoplastic cells (Reed Sternberg cells) produce cytokines to draw in other cells, so the mass is almost all composed of the reactive inflammatory cells
26
Differentiate intestinal and diffuse type of gastric carcinoma
Intestinal type = large irregular ulcers on lesser curvature of the antrum
-RF: intestinal metaplasia (seen in chronic gastritis from H. pylori or autoimmune)
Diffuse type = signet ring cells, desmoplasia thickens stomach wall
27
Celiac disease
(a) Associated immunodeficiency
(b) Antibodies present
Celiac disease
(a) Associated w/ IgA deficiency => if high suspicion remember to also check for IgG antibodies against tissue transglutaminase
(b) Anti-tissue transglutaminase, anti-endomysium (lining of individual nerve fibers), or anti-gliaden
28
Where does the virus that causes oral herpes lay dormant?
HSV-1 (causes majority of oral herpes cases) lays dormant in the ganglia of the trigeminal nerve
29
Acute promyelocytic leukemia- go to treatment
APL is due to t(15,17) that disrupts retinoic acid receptor needed for promyelocytes to mature => for tx give ATRA (retinoic acid derivative) to decrease blast burden b/c cells can now mature
30
Differentiate the two causes of chronic gastritis
(a) Location
(b) MC
(c) Mechanism
Chronic gastritis:
(b) H. pylori MC (90% of cases)
(a) H. pylori inflammation MC involves the antrum (distal portion, closest to duodenum)
(c) H. pylori sits on top of epithelium (doesn't invade) and releases ureases and proteases to weaken mucosal defenses
Autoimmune chronic gastritis: due to Ai destruction of gastric parietal cells
(a) Parietal cells concentrated in the fundus and body of the stomach
(c) Chronic inflammation causes intestinal metaplasia (intestinal mucosa w/ Peyer's patches are more able to handle stress of inflammation). No more parietal cells => achlorhydria and megaloblastic (pernicious) anemia
31
Cancers associated with
(a) Eosinophilia
(b) Basophilia
Blood cancers seen w/
(a) Eosinophilia = Hodgin lymphoma
- 2/2 IL-5 production
(b) Basophilia = CML
- recall: overproduction of mature granulocytes, especially basophils
32
When does pyloric stenosis present?
Pyloric stenosis is NOT PRESENT AT BIRTH!! the pyloric muscle hypertorphy (for unknown reason) starts after birth) so pts present w/ non-bilious vomiting around 2 wks of life
33
2 factors that determine risk of carcinoma in pts w/ Ulcerative Colitis
1. extend of colon disease
- of course the more colon that is inflammed, higher the risk
2. duration of disease
- generally don't get cancer w/o at least 10 yrs of disease
34
Name a cancer that can cause ectopic production of EPO
Renal cell carcinoma can produce EPO
=> can cause a hyperplastic (not neoplastic) proliferation of RBCs that may be hard to distinguish from polycythemia vera
35
Subclasses of AML
(a) Acute Promyelocytic Leukemia- MC cytogenetic abnormality
(b) Acute monocytic leukemia- how does this present?
(c) One seen in Downs syndrome pts before age 5
AML subsets
(a) APL: t(15,17) that disrupts retinoid acid receptor needed for promyelocyte maturation
(b) Acute monocytic leukemia presents w/ gum swelling b/c hte monoblasts infiltrate the gums
(c) Acute megakaryoblastic leukemia
36
Multiple myeloma
(a) Explain why you get bony lytic lesions
(b) Finding on serum protein electrophoresis
Multiple myeloma
(a) Plasma cells secrete osteoclast-activating factor => bony lytic lesions of vertebrae and skull and hypercalcemia
(b) M-spike due to monoclonal antibody production
37
Differentiate what would cause transmural vs. only mucosal infarction in the bowel
Transmural infarction due to arterial thrombosis/embolism (ex: AFib, vasculitis) or venous thrombosis (polycythemia vera)
While mucosal infarction (mucosa is farthest from blood supply) arises from low blood flow states like hypovolemia/shock
38
Explain a group of syndromes that can progress to AML
Myelodysplastic syndrome = neoplastic accumulation of mature cells in the myeloid lineage, so this can prgoress to neoplastic accumulation of immature cells w/ just a different mutation
-so neoplastic process of myeloid lineage but blasts are under 20%
= CML, P. vera, Essential thrombocytopenia
39
MC site of volvulus in
(a) Elderly
(b) Young adults
Volvulus most likely to develop in place w/ extra mesentery where it can twist on itself
(a) Elderly = sigmoid colon
(b) Cecum in young adults
40
Explain why H. pylori infection causes chronic gastritis
H. pylori sits on top of the gastric mucosa (doesn't invade the mucosa itself) and releases proteases and urases that weaken mucosal defenses and cause inflammation
41
Explain why Meckel's diverticulum may bleed (aka 2 yo p/w melena)
Meckel's diverticulum often has heterotopic gastric tissue in it that produces H+ that breaks down intestinal wall => bleeds
42
LN spread of esophageal malignancy
(a) Upper 1/3
(b) Middle 1/3
(c) Lower 1/3
LN spread depends on where in the esophagus
(a) Upper 1/3 to cervical LN
- squamous cell carcinoma 2/2 irritation
(b) Middle 1/3 to mediastinal or tracheobronchial nodes
(c) Lower 1/3 to celiac and gastric nodes
- adenocarcinoma from Barret's/GERD, b/c needs Barret's or else there wouldn't be glands in the esophagus to become cancerous
43
Differentiate leukemia and lymphoma
Both are neoplastic proliferation of cells from hematopoietic stem cell lines
Leukemia = when these cells stay in the blood
Lymphoma = when these cells form a mass (can be in LN or extranodal)
44
Describe the cardiac complication seen in carcinoid heart disease
(a) What kind of carcinoid tumors cause this?
(b) How to tell if pt will get R or L sided cardiac lesion?
Excess serotonin causes fibrosis of heart valves => right sided lesions such as TR
(a) Mets to liver, b/c venous drainage needs to bypass liver or else excess 5-HT is metabolized by MAO into 5-HIAA and excreted in urine and you don't get the clinical syndrome
(b) Carcinoid syndrome CANNOT cause left sided heart lesion b/c lung contains MAO that will convert 5-HT into 5-HIAA so the fibrosis-stimulating 5-HT doesn't reach the left heart
45
Differentiate Marginal Zone Lymphoma from Burkitt Lymphoma
(a) Cells
(b) Associated condition
Marginal Zone Lymphoma
(a) Neoplasia of small B cells
(b) Chronic inflammatory states: Hashimoto's, H. pylori gastritis, Sjogrens
Burkitt Lymphoma
(a) Neoplasia of intermediate sized B cells
(b) EBV infection
46
Name two places where Burkitt Lymphoma typically present
(a) Molecular cause
Burkitt Lymphoma = neoplastic proliferation of intermediate sized B cells
Clasically presents with:
- mass in jaw in African Americans
- mass in abdomen in sporadic form
(a) C-myc translocation
47
Celiac disease vs. tropical sprue- name 2 ways to differentiate
Tropical sprue is when small bowel villi are damaged due to an unknown organism- but key differentiation is that it's infectious
So topical sprue arises after infectious diarrhea and responds to abx
-also often occurs in tropical regions
Another big distinction = location
- Celiac disease involves duodenum
- Tropical sprue most prominent in jejunum and ileum
48
Which type of AML can be a medical emergency?
Acute promyelocytic leukemia can become a medical emergency
-promyelocytes have tons of Auer rods (crystal aggregates of MPO) which can activate the coagulation cascade and potentially cause DIC
49
Differentiate pleomorphic adenoma and mucoepidermoid carcinoma of the salivary glands
Pleomorphic adenoma = benign, both stromal and epithelial tissue, painless (b/c hasn't invaded facial nerve b/c benign)
Mucoepidermoid carcinoma = malignant, both mucinous and squamous cells, usually of parotid, commonly involves facial nerve (so facial palsy/pain)
50
Name the 3 features of carcinoid syndrome
2/2 excess 5-HT (serotonin) release
1. bronchospasm
2. diarrhea
3. flushing of skin
51
Classic cause of dysphagia to BOTH liquid and solid
When you can't swallow liquids too (and not progressive as in it started w/ solids and now it's both) think achalasia = esophageal dysmotility and inability of LES to relax
B/c need esophageal peristalsis and relaxed LES to let liquids into stomach too
52
Differentiate erosion from ulceration
First recall layers of the GI tract: mucosa --> submucosa --> muscularis propria --> serosa
Erosion = involves only mucosa (heals w/ full resolution)
Ulceration = extends into submucosa (heals w/ fibrosis/scaring)
53
Bacteria that causes lymphocytic (instead of neutrophilic) leukocytosis
Bordetella pertusis- bacteria that causes lymphocytic leukocytosis (usually seen in viral infections)
54
Which blood cancer do you think first when a teenager presents w/ a mediastinal/thymic mass?
T-ALL = acute lymphoblastic lymphoma
| lymphoma and not leukemia b/c the T cells aren't in the blood, they're making a mass in the thymus
55
Celiac disease
(a) Type of hypersensitivity
(b) Pathogenic antigen
(c) Associated derm finding
Celiac disease
(a) Type IV hypersensitivity b/c delayed T-cell response
(b) Gliaden is the part of gluten that is pathogenic
(c) Dermatitis herpetiform- IgA deposition at tip of dermal papillae cause small grouped vesicles that looks like (but has nothing to do with) herpes
56
Which region of the lymph node would be enlarged due to
(a) RA
(b) Early HIV
(c) Viral infection
(d) Reactive LN = LN draining cancerous tissue
(a, b) RA and early HIV cause hyperplasia in the follicular region
- chronic inflammatory cells (for RA), and follicular cells are CD4+ (early HIV)
(c) Viral infection causes expansion of paracortex (where the T cells are)
(d) LN draining cancerous tissue undergo hyperplasia of the sinus histiocytes (deep in the medulla)
57
Differentiate Sister Mary Joseph nodule and Krukenberg tumor
Sister Mary Joseph nodule = periumbilical nodule indicative of underlying malignancy
- usually gastric adenocarcinoma metastasized to the liver
- seen in intestinal type gastric adenocarcinoma
Krukenberg tumor = b/l ovarian metastasis from gastric carcinoma
-seen in diffuse type gastric adenocarcinoma
58
Differentiate the toxin in acute vs. chronic gastritis
Acute gastritis = breakdown of stomach wall from either too much acid or breakdown of mucosal barrier
Chronic gastritis from chronic inflammation- MC from H. pylori, also from autoimmune destruction
59
MC primary malignancy of bone
(a) Involved IL
Multiple myeloma = MC primary malignancy of bone
(a) IL-6
60
Adult onset asthma- buzzword for what dx?
Adult onset asthma- first r/o GERD
61
Esophageal web- buzzword for what dx?
Esophageal web = thin protrusion of esophageal mucosa that can cause partial obstruction
Buzzword for Plummer-Vinson syndrome
62
Myeloproliferative d/o of
(a) granulocytes
(b) Erythroblasts
(c) Megakaryoblast
(d) Plts
Myeloproliferative d/o = neoplastic proliferation of mature cells of the myeloid lineage
(a) Granulocytes, especially basophils = CML
(b) Erythroblasts = Polycythemia vera
(c) Megakaryoblasts = Myelofibrosis
2/2 oversecretion of PDGF
(d) Plts = Essential thrombocytopenia
63
What are Auer rods?
(a) Seen in what?
Auer rods = crystal aggregates of MPO
(a) Seen in AML = acute myeloblastic leukemias
64
Differentiate the two precursor lesions to squamous cell carcinoma of the mouth
Precursor lesions = leukoplakia (white plaque, not scraped away like candida) and erythroplakia (red plaque b/c vascularized)
-don't confuse this w/ hairy leukoplakia, which is NOT pre-malignant
65
Which chronic leukemia presents similarly to multiple myeloma
ATLL (Adult T cell Leukemia Lymphoma) = neoplastic proliferation of mature CD4+ T cells
-associated w/ HTLV-1 (Japan and Caribbean)
presents w/ lytic bone lesions and hypercalcemia (similar as MM)
But ATLL will have a rash (b/c CD4+ T cell proliferation => rash), while MM has no rash
66
Definition of acute leukemia
(a) How does this clinically present
Acute leukemia = neoplastic proliferation of immature blood cells (blasts) making up 20% or more of bone marrow
(a) Blasts crowd out bone marrow, so pt presents due to decrease in the other cell lines
- anemia
- leukopenia
- thrombocytopenia
67
What is Marginal Zone Lymphoma?
(a) Seen in what conditions?
(b) Tx for this in the gut
Marginal Zone is created from B cells from the germinal centers => need to be creating lots of inflam. response for this zone to proliferate
(a) Seen in chronic inflammatory states: Hashimotos, Sjogrens, H. pylori gastritis
(b) In the gut this can cause MALT, which can regress w/ H. Pylori eradication
68
Explain the clinical presentation of pts w/ lactose intolerance
Lactose enzyme not available to break down lactose into galactose and glucose => lactose remains in intestinal lumen and acts as osmotic diuretic => watery diarrhea
69
Infectious Mononucleosis
(a) Less common cause
(b) Part of spleen that enlarges
(c) Definitive test
Infectious Mono
(a) Usually by EBV, less commonly caused by CMV
- suspect CMV if monospot test is still negative after first week
(b) Periarterial lymphatic sheath of the white pul expands
(c) After positive monospot screening test, dx definitively w/ EBV viral capsid antigen
70
Blood cancer increased risk in Downs syndrome pts
(a) before age 5
(b) after age 5
Downs syndrome pts have an icnreased risk of malignancy
(a) Before age 5- Acute Megakaryoblastic leukemia = neoplastic proliferation of megakaryoblasts
- lack MPO
(b) After age 5- ALL (acute lymphoblastic leukemia)
- so acute leukemia (blasts over 20%) due to accumulation of lymphoblasts (lymphoblastic lineage- so split into T-ALL and B-ALL
71
Explain the following consequences of multiple myeloma
(a) Increased infection risk
(b) Rouleux formation
(c) Risk of which type of amyloidosis?
(d) Bence-Jones proteins
Multiple myeloma
(a) Decreased variability in cell immunity => increased risk of infection
(b) Rouleux formation of RBCs (stacks formed) b/c the increase in serum protein decreases the charges btwn RBCs
(c) Increased risk of AL amyloidosis 2/2 massive increase in IgL (immunoglobulin light chain)
(d) Bence-Jones = Ig light chain found in urine
72
Super random but what blood type is a risk factor for a certain GI cancer?
Blood type A is a risk factor for intestinal-type gastric carcinoma
73
Triple therapy for H. pylori eradication
PPI, amoxicillin, clarithromycin
74
Mutation implicated in most myeloproliferative d/o
JAK2-kinase mutation
| -associated w/ polycythemia vera, essential thrombocytopenia, and myelofibrosis
75
Leser-Trelat sign
Leser-Trelat sign = acute onset of tons of seborrheic keratoses ('stuck-on' dark lesions) = indicative of underlying cancer
-usually underlying gastric adenocarcinoma
76
Biopsy finding in duodenal ulcers
Duodenal ulcers- see hypertrophy of Brunner's glands (mucus-secreting glands)
77
Differentiate Curling and Cushing ulcers
Curling ulcer = ulcer due to severe burns causing hypovolemia. Hypovolemia => reduced blood flow to Gi tract so reduced removal of acid and reduced nutrients to barrier
Cushing ulcer = elevated ICP causes direct stimulation of vagus nerve, vagal stimulation secretes ACh that directly stimulates parietal cells into fundus and body of stomach to release more acid
78
Translocations seen in the small cell Non Hodgkins Lymphoma
(a) Follicular lymphoma
(b) Mantle cell lymphoma
Translocations
(a) Follicular lymphoma: t(14,18)
- Bcl2 w/ IgH, Bcl2 is needed to stabilize mitochondrial membrane and prevent apoptosis, but in these B cells undergoing somatic hypermutation apoptosis is needed => this translocation prevents B cells in the follicles from undergoing apoptosis as Bcl2 keeps c-myc in the mitochondria (and therefore unable to activate capsases)
(b) Mantle cell lymphoma: t(11,14)
- Cyclin D1 (cell cycle regulator, G1 --> S) w/ IgH (immunoglobulin heavy chain)
79
Which artery causes bleeding 2/2
(a) Rupture of posterior duodenal ulcer
(b) Rupture of gastric ulcer
(a) Posterior duodenal ulcer ruptures and causes bleeding from gastroduodenal artery (runs on the posterior border of the duodenum)
(b) While gastric ulcers are MC located on the lesser curvature of the antrum, where the left gastric artery runs
80
MC cause of appendicitis in children vs. adults
Children- lymphoid hyperplasia
Adults- fecolith (just a piece of fecal material) obstruction
81
Classic clinical presentation (including demographics) of IBD vs. IBS
IBD = young women (30s) w/ recurrent bouts of bloody diarrhea and abdominal pain
- diagnosis of exclusion
- subclassified into Crohns and UC
IBS = relapsing abdominal pain and change in bowel habits that improves w/ defecation, classically middle aged females
-biopsy normal
82
Explain what type of biopsy is needed to dx Hirschsprung disease
Need to do suction biopsy, can't just do regular biopsy
Regular biopsy will only give mucosa, while you need to get into the muscularis propria to see if the nerve plexi are missing to dx Hirschsprung
83
UC vs Crohn
(a) Full thickness
(b) Knife-like fissures vs. ulcers
(c) LLQ pain
(d) RLQ pain
(a) Crohns has full thickness lesions
- ulcers are defined as only mucosa and a bit of submucosa
(b) Knife-like fissures in Crohns b/c full thickness
(c) LLQ pain in UC b/c rectum then ascends (on left side)
(c) RLQ pain in Crohns b/c MC involves terminal ileum
84
UC vs Crohn
(a) Associated w/ PSC
(b) Effect of smoking
(a) UC associated w/ PSC
(b) Smoking is ironically protective against UC, but is a rsk factor for Crohns
- stupid, obv don't smoke anyway, but know that ironically smoking is protective against UC
85
Describe what specific points in the colonic wall are weakest => most susceptible to diverticula
Diverticula develop right where vasa recta (veins) transverse the muscularis propria
-b/c diverticula are outpouches of mucosa and submucosa thru the muscularis, so makes sense that they'd go where something else (the veins) are already making a hole)
86
2 main manifestations of Hereditary Hemorrhagic Telangiectasias
HHT: autosomal dominant d/o causing thin-walled blood vessels, especially in the
1. mouth (get telangiectasias on lips)
2. GI tract => presents w/ GI bleed
87
MC cause of ischemic colitis
(a) MC location involved
MC cause of ischemic colitis = atherosclerosis of the SMA
(a) Splenic flexure = SMA watershed region
88
Clinical presentation of ischemic colitis
Post-prandial abdominal pain
-b/c w/ meals you increase O2 demand, which can't be met by atherosclerotically narrowed vessel
89
Explain how aspirin is thought to be protective from adenoma-carcinoma sequence
In the 3rd step of the vogelgram (APC --> kRAS --> p53) you also see increase in COX expression to allow polyp to progress to carcinoma
-aspirin is a COX inhibitor => aspirin works on third step to impede progression of adenoma to carcinoma
90
Name the 3 steps of the vogelgram and how they fit into adenoma-carcinoma sequence seen in CRC
1. APC mutation- creates the risk for polyp formation
2. kRAS mutation- actual polyp formation
3. p53 mutation- transformation of adenomatous polyp into carcinoma
- also have increased COX expression here
91
Polyps w/ greater risk of progression to carcinoma
(a) Size cutoff
(b) Sessile vs. pedunculated
(c) Tubular vs. villous
CRC adenoma to carcinoma sequence
(a) Greater than 2 cm
(b) Sessile has higher risk of progression
- think it's easier to grow off a little stalk then horizontally on tissue (more contact w/ tissue)
(c) "villous is villain"- greater risk of progression from villous than tubular histology
92
Differentiate Gardner and Turcot syndrome
Both Gardner and Turcot syndrome are FAP (familial adenomatous polyposis- APC mutation on chromosome 5) variants w/ additional tumors
Gardner = FAP w/ fibromatosis (soft tissue tumors) and osteomas
Turcot = FAP w/ CNS tumors
93
What is Peutz-Jeghers syndrome?
Aut dominant d/o of hamartomatous (benign) polyps of the skin and GI tract
-huge increased risk of CRC
94
2 other cancers (besides CRC) that pts w/ HNPCC are at increased risk of
HNPCC = cancer syndrome 2/2 mutation in mismatch repair enzyme, leading to microsatellite instability
Increased risk of CRC, ovarian, and endometrial cancer
95
Differentiate the colonic carcinomas seen in HNPCC vs. FAP
FAP = APC mutation, so these cancers start as polyps and undergo adenoma-carcinoma sequence (APC, kRAS, then p53 mutation)
While HNPCC tumors arrive denovo (b/c mismatch repair enzyme mutated), not from polyps
-more commonly right sided
96
Currant jelly stools
Buzzword for intussusception
97
Differentiation clinical presentation of achondroplasia and osteogenesis imperfecta
Achondroplasia (impaired cartilage growth) => dwarfism
-short b/c long bones grow via endochondrial formation (on cartilage matrix) while skull and rib cage (unaffected) grow by intramembranous formation (w/o preexisting cartilage formation)
Osteogenesis imperfecta (defect in collagen I) => impaired bone formation => multiple fractures, blue sclera, hearing loss
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Mutation causing achondroplasia
Activating mutation in fibroblast growth factor that inhibits growth => impaired cartilage growth
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Explain blue sclera finding in osteogenesis imperfecta
OI => blue sclera b/c defect in collagen I exposes the choroidal veins that lie behind the thinned sclera
100
Explain the pathogenesis that causes osteopetrosis
Osteopetrosis = defect of bone resorption causing thick, heavy bone that easily fractures
MC caused by mutation in carbonic anhydrase II => can't make the acidic environment needed to remove Ca2+ from bone
Recall: need acid (carbonic anhydrase) to remove Ca2+ from bone, need alkaline environment to build bone (hence why alk phos released when osteoblasts are activated)
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Explain these findings of osteopetrosis
(a) Hearing impairment
(b) Renal tubular acidosis
(c) Anemia
Osteopetrosis = defect in bone resorption 2/2 mutation in carbonic anhydrase impairing acidic environment needed for bone breakdown
Bone can't be broken down => bone gets super thick and heavy
(a) Hearing and visual impairments are bone thickens and impinges cranial nerves
(b) RTA b/c w/o carbonic anhydrase, can't break down H2CO3 --> H+ (out in urine) for HCO3- to be taken back into body
(c) Anemia b/c bone marrow replaced by expanding bone/cortex
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Tx for
(a) Achondroplasia
(b) Osteopetrosis
(a) Achondroplasia = dwarfism but mental fxn life span and fertility are unaffected => no tx
(b) Osteopetrosis = can't break down bone due to carbonic anhydrase mutation (can't make acidic environment for osteclasts to work in)
- tx w/ bone marrow transplant: new osteoclasts (w/ functioning carbonic anhydrase) prodcued from new monocytes
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Effect of vitamin D deficiency in children vs. adults
Vit D deficiency in children => Rickets
-pigeon breast deformity, frontal bossing, rachitic rosary, bowing of legs
Vit D deficiency in adults => osteomalacia
-increased risk of fracture
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70 yo F fractures a bone- easy way to distinguish osteomalacia from osteoporosis
Osteomalacia (weak bones 2/2 vitamin D deficiency) vs. osteoporosis (reduction in trebecular bone mass) differentiated by simple lab test
Osteomalacia: low serum calcium and phosphate, elevated PTH and alk phos
Osteoporosis: normal labs!
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Paget disease
(a) Buzzword clinical presentation
(b) Unique lab finding
Paget disease = imbalance btwn osteoclast and osteoblast activity => abnormal deposition of bone
(a) Increasing hat size 2/2 skull enlargement
(b) Isolated elevation in alk phos
- no mineral abnormalities (normal Ca Phos)
- but osteoblasts are active => alk phos elevated
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2 complications of Paget disease of bone
Paget disease of bone = imbalance btwn osteoclast and osteoblasts leading to abnormal irregular bone deposition
2 complications
1. osteosarcoma = malignant tumor of osteoblast
2. high output heart failure: b/c AV shunts form in bone that heart has to push thru
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Tx for Paget disease of bone
Paget disease of bone = imbalance of osteoclast vs. osteoblast activity causing deposition of abnormal irregular bone
Tx = calcitonin (inhibits osteoclast fxn so stop chewing down bone)
Bisphosphonates: induces apoptosis of osteoclasts
108
Differentiate location of osteomyelitis in children vs. adults
Osteomyelitis: infection of marrow and bone via hematogenous spread
- transient bacteremia in children seeds metaphysis (growth plate)
- open wound bacteremia in adults seeds epiphysis (above metaphysis)
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Expected cause of osteomyelitis in
(a) Diabetics
(b) Sickle cell disease
(c) Sexually active young adult
(d) Cat/dog bite
(e) Overall MC cause
(a) Diabetes and IVDU- pseudomonas
(b) SCD- salmonella
(c) Sexually active young adult- Neisseria gonorrhea
(d) Cat/dog bite- pasteurella
(e) Overall, 90% cases caused by S. aureus
110
Differentiate osteoid osteoma and osteoblastoma
Both are benign tumors of bone
Osteoid osteoma: smaller (under 2cm), arises in cortex, bone pain that is relieved by aspirin
Osteoblastoma: larger (over 2cm), arises in vertebrae, pain NOT relieved by aspirin
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Bone tumor that arises from the
(a) Metaphysis
(b) Epiphysis
(a) Osteosarcoma = malignant tumor of osteoblasts that arises in the metaphysis of long bones
(b) Giant cell tumor = in young adults, arises in the epiphysis of long bones
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Ewing sarcoma
(a) Derived from what tissue?
(b) Xray appearance
(c) Where does it arise?
Ewing sarcoma = bone tumor in child 2/2 t(11;22)
(a) Derived from neuroectoderm
(b) Onion skin appearance on Xray
(c) Arises at diaphysis (shaft) of long bone, usually in males under 15
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Ewing sarcoma- how to differentiate from lymphoma
Both Ewing sarcoma and lymphoma may present as acutely inflammed joint w/ fever
Ewing sarcoma cells: small, round blue cells that resemble lymphocytes, will have t(11;12)
Translocation of 11;22 = characteristic for Ewing Sarcoma
114
Differentiate location of chondroma and chondrosarcoma
-cartilage tumors arise from the medulla
Chondroma = benign tumor of cartilage, arises in medulla of small bones of hands and feet (ex: fingers)
Chondrosarcoma = malignant tumor of cartilage, again arises in medulla but this time in pelvis or central skeleton
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Appearance of mets to bone
Metastatic tumors to bone are primarily osteolytic (punched out) lesions
One exception = prostate carcinoma- forms osteoblastic lesion
116
Explain the different clinical picture of osteoarthritis and RA
OA: stiffness in morning that worsens throughout the day (b/c worsens w/ use!)
RA: morning stiffness improves w/ activity b/c diffusing/moving around the inflammatory cells
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Hallmark tissue found in rheumatoid arthritis
Pannus = inflamed granulation tissue in the synovium = hallmark of RA
118
Differentiate joints involved in OA vs. RA
OA: both DIP (Heberden nodes) and PIP (Bouchard nodes)
RA: PIP, but DIP usually spared!!!
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2 complications of the chronic inflammation seen in RA
1. Anemia of chronic disease from increase in hepcidin (acute phasereactant)
2. Upregulate acute phase reactant SAA, SAA converted into AA that deposits in tissues => secondary amyloidosis
120
Name the triad seen in Reiter syndrome (seronegative spondyloarthropathies)
Reiter syndrome = arthritis, urethritis, and conjunctivitis
"can't see, can't pee, and can't climb a tree"
Seronegative b/c negative rheumatoid factor
121
Explain increased risk of gout in Lesch-Nyhan syndrome
Lesch-Nyhan syndrome = X-linked deficiency in HGPRT which is used to recycle hypoxanthine and guanine so they don't get shunted to uric acid.
W/o HGPRT hypoxanthine and guanine (therefore AMP and GMP, their precursors respectively) are all made into uric acid => excess uric acid precipitates in joints = gout
122
Positive ANA w/ malar rash
(a) w/ anti-dsDNA Ab
(b) W/ anti-Jo1 ab
(a) Lupus
| (b) Dermatomyositis
123
How to differentiate dermatomyositis and polymyositis
Besides absence of skin findings in polymyositis, can do muscle biopsy:
Dematomyositis: perimysial (periphery of muscle fiber) infalmmation
Polymyositis: enodmysial inflammation
124
One surgery that can improve symptoms of myasthenia gravis
Thymectomy b/c associated w/ thymic hyperplasia or thymoma
125
Grape-like mass protruding from vagina of 5 yo that stains desmin positive
Desmin positive stain characteristic of muscle, mass in vagina is classic site of rhabdomyosarcoma (malignant tumor of skeletal muscle)
-MC site overall is head and neck
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HPV serotypes
(a) Condyloma acuminatum
(b) Squamous cell carcinoma
(a) Condyloma acuminatum associated w/ HPV type 6 and 11 (low risk)
(b) SCC associated w/ high risk HPV types 16, 18, 31, 33
- explains how lack of circumcision may pose increased risk of penile cancer b/c foreskin acts as nidus for inflammation and irritation
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(a) MC congenital male reproductive abnormality
(b) MC testicular tumor
(c) MC testicular tumor in children
(a) Cryptorchidism = failure of testicle to descend into scrotal sac
(b) MC testicular tumor = germ cell tumor (95%)
- most are mixed germ cell tumors
(c) MC testicular tumor in children = yolk sac (endodermal sinus) tumor
- subtype of non-seminoma germ cell tumor
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Indication for orchiopexy
Orchiopexy = surgically move down undescended testes (to treat cryptorchidism)
- most will spontaneously regress, so only do the surgery if male is almost 2 and it hasn't descended
- do before age 2 b/c can be associated w/ testicular atrophy/infertility b/c testicles need colder temp of outside than body temp
129
Ddx for granulomas in the seminiferous tubules
Ddx = Tb and autoimmune orchitis (orchitis = testicular inflammation)
Differentiate by AFB
130
MC cause of prostatitis and orchitis
Separated by age group
Young sexually active males = N. gonorrhea and chlamydia trachomatis
Older adults see spread of UTI infxns to reproductive tract = E. Coli and Pseudomonas
131
Type of infarction seen in testicular torsion
Hemorrhagic infarction (not ischemic) b/c the torsion first obstructs the vein (collapsible structure) => arterial blood flow enters dead tissue causing hemorrhage
132
Differentiate varicocele and hydrocele
Varicocele = dilation of spermatic vein due to impaired lymphatic drainage (obstruction!)
Hydrocele = fluid collection in the tunica vaginalis (scrotal sac)
133
Malignancy associated w/ varicocele
Varicocele = dilation of spermatic vein (palpate 'bag of worms' on physical exam)
L. varicocele can be due to obstruction of left renal vein (which indirectly then drains blood into IVC), renal cell carcinoma classically spreads to left renal vein
=> L. varicocele associated w/ L. RCC
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Varicocele more commonly left or right sided?
Left sided b/c left scrotal vein drains indirectly into IVC via the left renal vein, while right scrotal vein drains directly into IVC
135
How to differentiate hydrocele from malignant process?
Hydrocele = fluid in the scrotum => can be transilluminated
While testicular tumor
136
How to diagnose testicular tumors
DONT BIOPSY! Risk of seeding to the scrotum, and 95% are germ cell tumors anyway which are malignant => just do radical orchiectomy w/o biopsy
137
Germ cell tumors: seminoma vs. non-seminoma
(a) Gross appearance
(b) Prognosis
Seminoma (resemble spermatogonia)
(a) Homogenous non-hemorrhagic non-necrotic mass
(b) Highly responsive to radiotherapy, metastasize late, excellent prognosis
Non-seminoma (not spermatogonia like) = embronal carcinoma, yolk sac tumor, choriocarcinoma, teratoma
(a) Hemorrhagic mass w/ necrosis
(b) Variable response to tx and often met early => worse prognosis
138
Teratoma: M vs. F
Teratomas in females are benign, while they are malignant in males
Recall: teratoma = tumor composed of mature fetal tissue from 2-3 embryonic layers (at least 2 embryonic layers)
139
Cause of hydrocele in adults vs. children
Hydrocele = fluid collection in the tunica vaginalis (scrotal sac)
In children 2/2 incomplete closure of the processes vaginalis, leading to communication w/ the peritoneal cavity
Caused by blockage of lymphatic drainage in adults
140
DRE findings seen in
(a) Acute prostatitis
(b) BPH
(c) Potential prostatic adenocarcinoma
Digital rectal exam
(a) Acute prostatitis- feel tender and boggy prostate
(b) BPH- diffusely enlarged
(c) Irregular mass on posterior peripheral surface
141
Dx acute and chronic prostatitis
Can dx by WBC in prostatic secretions
Can culture prostatic secretions- will see bacteria in acute, probs wont grow any bacteria in chronic
142
Briefly describe the Gleason grading system for staging prostate cancer
Gleason grading system- graded on architecture alone, NOT nuclear atypia
So grading is unique in that multiple regions are assessed for architecture, while nuclear atypia is not included in the grading
143
MC location of prostatic cancer mets
(a) Type of lesion seen
MC location of prostate mets = lumbar spine (p/w lower back pain) and pelvis
(a) Osteoblastic lesion
- key here b/c most mets present as osteolytic (punched out) lesions, but not prostate!!
144
Clinical presentation of metastatic prostate cancer
(a) Lab findings
MC spreads to lumbar spine or pelvis => presents w/ lower back pain
(a) Elevated alk phos, PSA, and prostatic acid phosphate
145
Medical vs. surgical tx for prostate cancer
If prostate cancer is localized do prostatectomy
Advanced disease: tx w/ hormone suppression to reduce DHT
- Leuprolide = continuous GnRH analogue
- Flutamide = competitive inhibitor of androgen receptor
146
Compare the two medical tx for BPH
Treating BPH
1. Alpha1 antagonist (terazosin) to relax smooth muslce
- can also help lower BP
- more immediate result but need to take everyday
2. 5alpha reductase inhibitor: reduces conversion of T --> DHT => reduced stimulation on stromal epithelium
- but takes months to have effect b/c actually works to shrink the prostate
- also can be used for male pattern baldness
- side effects may be gynecomastia and sexual dysfunction
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PSA levels
(a) Normal
(b) BPH
(c) Concerning for cancer
PSA = prostate-specific antigen, produced by prostate glands to liquefy semen
(a) Normal is under 4 ng/mL
(b) BPH shows slight elevation of 4-10, b/c more glands = more PSA produced
(c) Normal PSA increases w/ age, normal can be up to 7.5 for males in their 70s, but anything over 10 is worrisome for cancer at any age
