Pathology Infectious Disease Intro: Lecture 15

Front 1

Tumor Marker: PSA

Back 1

Prostate cancer

Front 2

Tumor Marker: Prostate cancer

Back 2

PSA

Front 3

Tumor Marker: CEA

Back 3

Colorectal/Pancreatic

Front 4

Tumor Marker: Colorectal/Pancreatic

Back 4

CEA

Front 5

Tumor Marker: CA 19-9

Back 5

Pancreatic

Front 6

Tumor Marker: Pancreatic

Back 6

CA 19-9

Front 7

Tumor Marker: Alpha-fetoprotein

Back 7

Hepatic/Yolk sac

Front 8

Tumor Marker: Hepatic/Yolk sac

Back 8

Alpha-fetoprotein

Front 9

Tumor Marker: Beta-HCG

Back 9

Choriocarcinoma/Molar pregnancy

Front 10

Tumor Marker: Choriocarcinoma/Molar pregnancy

Back 10

Beta-HCG

Front 11

Tumor Marker: CA 125

Back 11

Ovarian cancer

Front 12

Tumor Marker: Ovarian cancer

Back 12

CA 125

Front 13

Tumor Marker: S-100

Back 13

Melanoma/Astrocytoma

Front 14

Tumor Marker: Melanoma/Astrocytoma

Back 14

S-100

Front 15

Tumor marker: Thyroglobulin

Back 15

Thyroid cancer

Front 16

Tumor marker: Thyroid cancer

Back 16

Thyroglobulin

Front 17

Tumor marker: Calcitonin

Back 17

Medullary carcinoma of Thyroid

Front 18

Tumor marker: Medullary carcinoma of Thyroid

Back 18

Calcitonin

Front 19

Tumor marker: Catecholamines

Back 19

Pheochromocytoma/Neuroblastoma

Front 20

Tumor marker: Pheochromocytoma/Neuroblastoma

Back 20

Catecholamines

Front 21

Tumor marker: TRAP stain (tartrate resistant acid phosphatase

Back 21

Hairy cell leukemia

Front 22

Tumor marker: Hairy cell leukemia

Back 22

TRAP stain (tartrate resistant acid phosphatase

Front 23

Tumor marker: Alkaline phosphatase

Back 23

Mets to bones, Paget’s disease of bone

Front 24

Tumor marker: Mets to bones, Paget’s disease of bone

Back 24

Alkaline phosphatase

Front 25

Translocations: t (9;22)

Back 25

CML (bcr-abl)

Front 26

Translocations: CML (bcr-abl)

Back 26

t (9;22)

Front 27

Translocations: t (8;14)

Back 27

Burkitt’s lymphoma (c-myc)

Front 28

Translocations: Burkitt’s lymphoma (c-myc)

Back 28

t (8;14)

Front 29

Translocations: t (14;18)

Back 29

Follicular lymphoma (bcl-2)

Front 30

Translocations: Follicular lymphoma (bcl-2)

Back 30

t (14;18)

Front 31

Translocations: t (15;17)

Back 31

AML M3

Front 32

Translocations: AML M3

Back 32

t (15;17)

Front 33

Translocations: t (1;14)

Back 33

T-cell Lymphoblastic lymphoma

Front 34

Translocations: T-cell Lymphoblastic lymphoma

Back 34

t (1;14)

Front 35

Translocations: t (11; 22)

Back 35

Ewing’s sarcoma

Front 36

Translocations: Ewing’s sarcoma

Back 36

t (11; 22)

Front 37

Translocations: t (11; 14)

Back 37

Mantle cell lymphoma (bcl-1)

Front 38

Translocations: Mantle cell lymphoma (bcl-1)

Back 38

t (11; 14)

Front 39

Translocations: t (11; 18)

Back 39

MALT lymphoma (API-2)

Front 40

Translocations: MALT lymphoma (API-2)

Back 40

t (11; 18)

Front 41

Translocations: t (1; 14)

Back 41

MALT lymphoma (bcl-10)

Front 42

Translocations: MALT lymphoma (bcl-10)

Back 42

t (1; 14)

Front 43

Case 1. 70 y.o. female with fatigue. No hemoptosis or vaginal bleeding. Normal physical exam except for pallor.

CBC:
Hgb 5.9
MCV 56.2
RDW 20.2
WBC 5,900
Plt 383,000

1a. The RBCs show?
A. Macrocytosis
B. Hyperchromasia
C. Spherocytosis
D. Schistocytosis
E. Anisopoikilocytosis

1b. What lab result would you expect?

A. Elevated serum ferritin
B. Elevated serum iron
C. High serum iron and low TIBC
D. Low serum iron and high TIBC
E. Low serum iron and low TIBC

1c. Before the patient leaves your office you should?

A. Order TSH and T3
B. Order TSH and T4
C. Prescribe multivitamins with iron
D. Perform stool exam for occult blood
E. Perform stool exam for hookworms and other parasites

Back 43

1a. The RBCs show? E

Why are the platelets increased? Platelets are often increased in iron deficiency anemia. Why? Because Erythropoietin is increased in iron deficiency anemia, and Erythropoietin stimulates the RBC series and the megakaryocytes, so it's not unusual to see A LOT of platelets. ( Normal platelets = 100,000-200,000)

1b. What lab result would you expect? D

TIBC = iron binding capacity

Ferritin will be low.

1c. Before the patient leaves your office you should? D - In an older person with iron deficiency anemia will most likely have occult blood in their stool because of colon cancer.

Front 44

Case 2. 34 y.o. female with 2-day history of fever, petichiae and hematuria; also headaches and mental confusion.

CBC:
Hgb 7.0
MCV 77
RDW 23
WBC 17,000
Plt 14,000

2a. Describe the RBCs
A. Normochromic
B. Microcytic
C. Spherocytes and schistocytes
D. Drepanocytes and schistocytes
E. Howell-Jolly bodies

2b. Diagnosis?
A. Sickle cell anemia
B. Hereditary spherocytosis
C. Thrombotic thrombocytopenic purpura (TTP)
D. Anemia of chronic disease secondary to hypothyroidism
E. Folate deficiency

2c. What test result would you expect?

A. D dimer elevated
B. Haptoglobin elevated
C. Plasma free hemoglobin decreased
D. BUN normal
E. Urine protein negative

Back 44

There's fever, thrombocyopenia probably, renal problems, CNS problems, and the CBC shows schistocytes. What's missing in the CBC? Platelets

These findings are consistent with micro-angiopathic hemolytic anemia.

2a. Describe the RBCs: C
(Drepanocyte = the name for sickled red cells)

2b. Diagnosis? C

(If it were HUS, you'd see a child with renal but NO CNS disease. Cause = E. Coli)

2c. What test result would you expect? A - D-Dimer = the marker that picks up the crosslinks of fiber that are seen in DIC and MAHA

B - Haptoglobin should be low because this is a hemolytic anemia
C. Plasma Free Hemoglobin should be increased becasue of hemolytic anemia
D. BUN shouldn't be normal because there's renal disease.
E. Urine protein should be positive because of the renal disease

Front 45

Case 3. 34 y.o. male in for routine physical has pallor and icterus; splenomegaly on PE

CBC:
Hgb 11
MCV 84
WBC 6,000
Plt 350,000

3a. Describe the RBCs
A. Normochromic
B. Schistocytosis
C. Microcytic
D. Spherocytosis
E. Hypochromic

3b. What test should you order to confirm your diagnosis?
A. Serum iron
B. Osmotic fragility
C. Reticulocyte count
D. Malaria screen
E. D dimer

Back 45

3a. Describe the RBCs: D - The blood smear shows several small hyper-chromic cells.

3b. What test should you order to confirm your diagnosis? B - this patient has hereditary spherocytosis, and their RBC hemolyze easier than normal RBCs

Front 46

Case 4. 37 y.o. female treated lifelong for a seizure disorder complains of fatigue and lightheadedness

CBC:
Hgb 6
MCV 130
WBC 6,000
Plt 220,000

4a. All of the following correctly describe the RBCs EXCEPT:
A. Normochromic
B. Macrocytic
C. Anisocytosis
D. Ovalocytosis
E. Spherocytosis


4b. What findings on the bone marrow aspirate suggest folate deficiency?
A. Hyposegmented neutrophils
B. Hypocellularity
C. Giant bands and hypersegmented neutrophils
D. Miniature bands and hypersegmented neutrophils
E. Hypersegmented blasts and promyelocytes

Back 46

This patient is on long term Dilantin. (A side effect of Dilantin is hyperplasia of the gums) - they prob. have a nutritional deficiency. Dilantin interferes with the absorption of folate.

Blood smear: PMNs are hyper-lobulated

CBC: Macrocytic RBCs

4a. All of the following correctly describe the RBCs EXCEPT: E (Since they're big, this is anisocytosis)

4b. What findings on the bone marrow aspirate suggest folate deficiency? C

Front 47

LEUKEMIA: Acute

Back 47

LEUKEMIA: Acute

- ALL and AML
- Hi/Low WBC
- Rapidly fatal if untreated; anemic and thrombocytopenic
- Curable

Front 48

LEUKEMIA: Chronic

Back 48

LEUKEMIA: Chronic

- CLL and CML
- Always high WBC
- Slowly prgressive- patient lives many years
- Difficult to cure

Front 49

Back 49

Micro-angiopathic hemolytic anemia: (MAHA)

Seen in:
1. DIC
2. TTP
3. HUS

You can see fragmented RBCs because the fibrin strands that occur in the microvasculature, chop up the RBCs. These are called schistocytes and the spherocytes are little round ones.

Front 50

Back 50

Reticulocytes:

If you want to be sure of what the reticulocyte count is, you can do a reticulocyte stain and see what percentage of the cells are reticulocytes.

When do you do this?
In a patient with iron deficiency anemia. In iron deficiency anemia, the reticulocyte count is very low.

If the normal is 1%, this patient may have .1%, but with iron replacement therapy, they may go up to 3%.

Front 51

Back 51

Iron deficiency anemia

The lymphocyte is used to see if the RBC are the normal size. the size of the nucleus of the lymphocyte should be the same size as a RBC.

The RBC are small = microcytic, and a lot of them look like donuts = hypochromic, and there are funny shaped RBC = Poikilocytosis.

A combo of abnormal size and shape = anisocytosis

Front 52

Back 52

Due to B-12 or folate deficiency, you see enlarged RBCs that are often oval in shape. Also, the neutrophils have extra lobes. Instead of 3, you see 5-7

Front 53

What do you see histologically in iron deficiency anemia?

Back 53

Iron deficiency anemia

The lymphocyte is used to see if the RBC are the normal size. the size of the nucleus of the lymphocyte should be the same size as a RBC.

The RBC are small = microcytic, and a lot of them look like donuts = hypochromic, and there are funny shaped RBC = Poikilocytosis.

A combo of abnormal size and shape = anisocytosis

Front 54

What do you see histologically in a blood smear from a person with B-12 or folate deficiency?

Back 54

Due to B-12 or folate deficiency, you see enlarged RBCs that are often oval in shape. Also, the neutrophils have extra lobes. Instead of 3, you see 5-7

Front 55

What are the types of acute leukemia?

Back 55

1. Lymphoblastic leukemia
2. Myeloblastic leukemia
3. Monoblastic leukemia - associated with infiltration of the oral cavity. Therefore a patient with Acute leukemia and big gums or ulcers in their mouth, then think monoblastic leukemia
4. Pro-myelocytic leukemia aka hyper-granular leukemia is the one that a rapid diagnosis is critical because these patients develop DIC. All of these granules trigger DIC, and they can die rapidly. But, if you treat these patients with retinoic acid, you can get a good remission. In addition to the DIC, these patients get MAHA.

Front 56

5a. In Acute Leukemias you will almost always find:
A. Normal hct, normal platelets
B. Normal hct, decreased platelets
C. Decreased hct, increased paltelets
D. Anemia, thrombocytopenia
E. WBC count >100,000

Back 56

5a. In Acute Leukemias you will almost always find: D

Front 57

5b. In Chronic Leukemias you will almost always find:A. Anemia, thrombocytopenia
B. WBC count >50,000
C. Normal hct, increased platelets
D. Anemia, thrombocytosis
E. Circulating blasts

Back 57

5b. In Chronic Leukemias you will almost always find: B

Front 58

Back 58

Lymphoblastic leukemia with open chromatin.

These cells:
1. are 2x the size of a RBC
2. nucleoli

Front 59

Back 59

Of you think it's ALL you can do a PAS stain.

Lymphoblasts are PAS +
Myeloblasts are PAS -

Front 60

Back 60

Myeloid Precursors: The Myeloid series can also become malignant.

Front 61

Back 61

Immature granulocytes LEFT SHIFT): This is a proliferation of all of the cells to the left. There are neutrophil, bands and immature myeloid cells. This could be a leukemoid reaction, OR it could also be CML because there are some cells that may be blasts

Front 62

Back 62

CML: These can be a little confusing so you do a LAP score.

Front 63

Back 63

Sometimes it's hard to distinguish CML from a leukemoid rxn. Therefore a LAP score is needed.

Left: LAP (leukemoid) - if it is a leukemoid rxn, most of the cells will stain with the LAP so the LAP is high
Right: LAP (CML) - in CML these are abnormal cells, and none of them stain so LAP is LOW

LAP Normal - Normal Person
LAP High - Leukemoid Rxn
LAP Low - CML

Front 64

Back 64

CML vs AML

Both are myeloid leukemias, but in AML, you see nothing but blasts. In CML, you see a mix of blast-like cells, and also some later, more differentiated forms.

Front 65

Back 65

Left: AML
Why? There are many nucleoli, big cells (blasts), but NO granules or auer rods. (But, this could be ALL, unless... you find an auer rod)

Right: This has an auer rod in the cytoplasm therefore that is AML.

AUER RODS ONLY OCCUR IN AML!!!

Front 66

Back 66

AML M1 vs AML M2

M1 and M2 usually don't have auer rods. M2 may or may not have an auer rod.

Front 67

Back 67

AML M3 vs AML M4

M3: Has a lot of granules and auer rods

M4: a myelo-monocytic leukemia, and shares features of both types of leukemia

Front 68

Back 68

M5a vs M5b

Front 69

Back 69

M6 vs M7

Front 70

Back 70

M6 vs M7

Front 71

Case 6. 25 y.o. male with fever, recurrent URIs and submandibular swelling; also poor wound healing

CBC:
Hgb 9.9
MCV 106.3
WBC 7.9 (70% “abnormal cells”)
Plt 50,000

6a. Diagnosis?
A. ALL
B. AML
C. CLL
D. CML
E. Hereditary spherocytosis

6b. Which test on a bone marrow aspirate confirms your diagnosis?
A. MPO (-)
B. MPO (+)
C. PAS (+)
D. Iron stain (Prussian blue)
E. Leukocyte alkaline phosphatase = 20

Back 71

The blood smear shows auer rods, Therefore...AML

6a. Diagnosis? B

6b. Which test on a bone marrow aspirate confirms your diagnosis? B

Front 72

Case 7. 6 y.o. male with URIs, headache, bone pain and easy bruising; axillary and cervical lymphadenopathy; hepatosplenomegaly.

CBC:
Hgb 9
MCV 82
WBC 92,000 (86% abnormal)
Plt 18,000

7a. Diagnosis?
A. ALL
B. AML
C. CLL
D. CML

7b. What test results are expected on a bone marrow aspirate?
A. MPO (+), PAS (+)
B. MPO (-), PAS (-)
C. TdT (+), Precursor B cell (+)
D. TdT (-), Precursor T cell (+)
E. Sudan black B (+); CD 10 (-)

Back 72

Young boy. Peripheral blood smear shows blasts - butt cells. Platelets are gone. Based on this alone it may be ALL or AML. But, because the boy is 6 years old, it's probably ALL. WBC is very high.

7a. Diagnosis? A

7b. What test results are expected on a bone marrow aspirate? C

Front 73

Case 8. 15 y.o. male with flulike symptoms; axillary and cervical lymphadenopathy; gums are thick and bleeding

CBC:
HGB 9
MCV 90
WBC 42,000 (88% abnormal)
Plt 22,000

BM Bx results
MPO (-)
PAS (-)
Sudan Black B (-)
Non-specific esterase (++)
Serum lysozyme 162 (4-15 normal)

8. Diagnosis
A. AML (FAB M1)
B. AML (FAB M3)
C. AML (FAB M5)
D. ALL (L1)
E. Infectious mononucleosis

Back 73

8. Diagnosis: C

Non-specific esterase (++) and
Serum lysozyme 162 (4-15 normal) point to monoblasts. Also, M5 caused mouth ulceration and the person had bleeding gums.

Front 74

Case 9. 39-year-old female has routine workup for fibrocystic disease of breast; splenomegaly present

CBC:
Hgb 13
MCV 96
WBC 133,000 (seg 56, band 15, meta 13, myelo 4, pro 3); baso 1, eo 1
Plt 130,000

9. What test should you order on a bone marrow aspirate?
A. MPO
B. PAS
C. Sudan black B
D. LAP
E. TRAP

Back 74

Blood Smear shows a high WBC count, platelets are present.

Could this be a leukemoid rxn (a normal rxn to infection)? NO, why? because leukomoid rxns only get WBC counts up to 60,000-70,000, never over 100,000. So, with this many myeloid forms, it's CML.

9. What test should you order on a bone marrow aspirate? D

High LAP: Leukemoid
Low LAP = CML

All of the rest are tests for acute leukemia.

Front 75

10. 30-y.-o. female; anemia, thrombocytopenia; CBC- blasts w. Auer rods, schistocytes. Diagnosis?

A. ALL
B. AML, M1
C. AML, M3
D. AML, M5
E. TTP

Back 75

C

Front 76

Lymphomas: Hodgkin

Back 76

Lymphomas: Hodgkin

Hodgkin

Reed-Sternburg Cells
Often curable

Front 77

Lymphomas: Non-Hodgkin Lymphoma

Back 77

Lymphomas: Non-Hodgkin Lymphoma

Non-Hodgkin Lymphoma

Low grade- slowly progressive, rare cure. Why? Because when found, they're usually high stage and they're spread throughout the body.
High grade- rapidly progressive; a minority are curable. Why? Because some present at a lower stage and tend to be localized

Front 78

HD vs NHL

Back 78

Hodgkin

Stage important
Few malignant cells
< cell-mediated
Localized- and can be treated with radiation

Non-Hodgkin

Grade important
Mostly lymphoma
< humoral
Systemic- and can be treated with chemotherapy

Front 79

Back 79

Myeloperoxidase (MPO): This stain is positive in AML (M1-M4), and PAS negative.

(Lymphoblasts are PAS positive and MPO negative.)

Front 80

Back 80

Sudan black B: This stain is positive in M5

(Non-specific esterase is also positive in M5)

Front 81

Back 81

Non-specific esterase: This stain is positive in M5

(Sudan Black stain is also positive in M5)