Neoplasia/Hematology - Mechanisms of Disease - Acute Leukemias; Myelodysplastic Syndromes; CML; Myeloproliferative Diseases

Question 1

Acute leukemias can be thought of as disorders characterized by a block in leukocyte _____________.

Answer 1

Acute leukemias can be thought of as disorders characterized by a block in leukocyte differentiation.

Question 2

Chronic leukemias can be thought of as disordered/increased leukocyte ____________.

Answer 2

Chronic leukemias can be thought of as disordered/increased leukocyte proliferation.

Question 3

How could you easily differentiate between an acute and a chronic leukemia via a review of the peripheral blood smear?

Answer 3

Presence of >20% blasts = acute leukemia

Question 4

AML is mostly a disease of what median age group?

Answer 4

Median: 67 years of age

Question 5

True/False.

AML is typically characterized by concurrent leukocytosis, thrombocytosis, and variable erythrocyte levels.

Answer 5

False.

AML is typically characterized by pancytopenia with elevated blasts.

Question 6

Is splenomegaly typically seen in AML or CML or both?

Answer 6

CML

Question 7

True/False.

Splenomegaly and lymphadenopathy are somewhat unusual in most types of AML.

Answer 7

True.

Question 8

The pancytopenia seen in AML means that patients may present with what sort of S/Sy?

Answer 8

Pallor/fatigue/SoB (anemia);

infection (leukopenia);

bleeding (thrombocytopenia)

Question 9

Why is AML characterized by pancytopenia?

Answer 9

Bone marrow infiltration by immature (clonal) malignant cells.

Question 10

The peripheral blood in AML usually shows a high number of what?

Answer 10

Blasts (>20%)

Question 11

The bone marrow in AML is almost always ______cellular.

Answer 11

The bone marrow in AML is almost always hypercellular (filled with blasts).

Question 12

True/False.

If you do not see Auer rods on peripheral smear, it is not AML.

Answer 12

False.

Auer rods are pathognomonic for AML; however, their absence does not rule out AML.

Question 13

In most instances, blasts need to comprise at least ___% of white blood cells in the peripheral blood or at least ___% of bone marrow aspirate cellularity to make a diagnosis of AML.

Answer 13

In most instances, blasts need to comprise at least 20% of white blood cells in the peripheral blood or at least 20% of bone marrow aspirate cellularity to make a diagnosis of AML.

Question 14

Patients with AML typically require what in addition to their chemotherapy?

Answer 14

Antibiotics + transfusions

(for leukopenia and thrombocytopenia)

Question 15

Chemotherapy for AML, the mainstay of therapy, is divided into what two phases?

Answer 15

1. An early induction phase (to establish remission)
2. A later consolidation phase (to maintain remission)

Question 16

What can be used in AML treatment either as consolidation or if the disease relapses?

Answer 16

Bone marrow transplantation (autologous or allogeneic)

Question 17

AMLs with t(8;21), t(16;16), or t(15;17) have a(n) _________ prognosis.

AMLs with t(9:11) have a(n) _________ prognosis.

AMLs with no translocations have a(n) _________ prognosis.

Answer 17

AMLs with t(8;21), t(16;16), or t(15;17) have a good prognosis.

AMLs with t(9:11) have an intermediate prognosis.

AMLs with no translocations have a poor prognosis.

Question 18

True/False.

The overall long-term survival of patients diagnosed with AML is only ~25-30%.

Answer 18

True.

Question 19

What medication makes up an especially major portion of AML treatment?

Answer 19

Cytarabine

Question 20

Describe the WHO classification of AML:

1. AML with recurrent ________ abnormalities
2. AML with ________-related changes
3. Therapy-related myeloid neoplasms
4. AML, not otherwise specified.

Answer 20

Describe the WHO classification of AML:

1. AML with recurrent genetic abnormalities
2. AML with myelodysplasia-related changes
3. Therapy-related myeloid neoplasms
4. AML, not otherwise specified.

Question 21

Describe the WHO classification of AML:

1. AML with recurrent genetic abnormalities
2. AML with myelodysplasia-related changes
3. ________-related myeloid neoplasms
4. AML, not otherwise ________.

Answer 21

Describe the WHO classification of AML:

1. AML with recurrent genetic abnormalities
2. AML with myelodysplasia-related changes
3. Therapy-related myeloid neoplasms
4. AML, not otherwise specified.

Question 22

Which form of AML is susceptible to treatment with all-trans retinoic acid (tretinoin)?

Answer 22

Acute promyelocytic leukemia

(AML subtype M3 in FAB classification)

Question 23

Acute promyelocytic leukemia is almost always characterized by a t(15;17) translocation, resulting in fusion of what genes?

Answer 23

RARA-PML fusion protein from RARA and PML genes

(Retinoic acid receptor-alpha; promyelocytic leukemia)

Question 24

Acute promyelocytic leukemia is almost always characterized by production of the RARA-PML fusion protein. This results from translocation of what chromosomes?

Answer 24

t(15;17)

Question 25

What is commonly seen within the blasts seen in a peripheral smear of a patient with AML? What is overly expressed in these cells to produce this finding?

Answer 25

**Auer** rods; **myeloperoxidase**

Question 26

What does the RARA-PML fusion protein of acute promyelocytic leukemia do?

Answer 26

**Inhibits** **differentiation** | (acts as a DNA regulator)

Question 27

What is the most common leukemia seen in children?

Answer 27

ALL

Question 28

ALL is most commonly seen in what populations?

Answer 28

Children; the elderly (peaks at **\<6 years** and **\>60 years**)

Question 29

What are the two main subtypes of ALL?

Answer 29

1. B-cell ALL 2. T-cell ALL

Question 30

Clinically, patients with ALL present identically to patients with ____ except that splenomegaly and lymphadenopathy are more common.

Answer 30

Clinically, patients with ALL present identically to patients with **_AML_** except that splenomegaly and lymphadenopathy are more common.

Question 31

Patients with ALL present clinically identical to patients with AML except that ___________ and ___________ are more common.

Answer 31

Patients with ALL present clinically identical to patients with _AML_ except that **_splenomegaly_** and **_lymphadenopathy_** are more common.

Question 32

Which form of ALL is _much_ more likely to present with anterior mediastinal masses?

Answer 32

T-cell ALL

Question 33

**True/False**. B-ALL is typically a disease of the peripheral blood +/- bone marrow blood +/- extramedullary sites: CNS, lymph nodes, spleen, liver, and testis.

Answer 33

**False**. Typically a disease of the ***bone*** ***marrow*** +/- ***peripheral*** ***blood*** +/- extramedullary sites: CNS, lymph nodes, spleen, liver, and testis.

Question 34

What are the two main WHO categories of ALL? Which is associated with a worse prognosis (answer bolded)?

Answer 34

1. Non-specified 2. Recurrent genetic abnormalities (t(**9**;**22**))

Question 35

You note that a patient has an elevated number of blasts in their bone marrow and on peripheral smear. How do you differentiate whether these are myeloblasts or lymphoblasts?

Answer 35

**Immunohistochemistry** and/or **flow cytometry**

Question 36

**True/False**. Pediatric cases of either ALL or AML tend to be very treatable.

Answer 36

**True**.

Question 37

**True/False**. Adult cases of either ALL or AML tend to be very treatable.

Answer 37

**False**. Much worse prognosis than pediatric cases.

Question 38

ALL has a predilection for sanctuary sites such as the \_\_\_\_, making intra\_\_\_\_\_\_\_\_ treatment necessary.

Answer 38

ALL has a predilection for sanctuary sites such as the **_CNS_**, making intra**_thecal_** treatment necessary.

Question 39

ALL with a t(9;22) is associated with a ________ outcome. ALL with a t(12;21) is associated with a ________ outcome.

Answer 39

ALL with a t(9;22) is associated with a **_poor_** outcome. ALL with a t(12;21) is associated with a **_good_** outcome.

Question 40

Identify which of the following are mutations relevant to evaluation/prognosis/treatment of AML: ## Footnote ***NPM1*** ***FLT3 ITD*** ***FLT3 TKD*** ***IDH1*** ***IDH2*** ***P53*** ***C-Kit***

Answer 40

_All_ of them ## Footnote ***NPM1*** ***FLT3 ITD*** ***FLT3 TKD*** ***IDH1*** ***IDH2*** ***P53*** ***C-Kit***

Question 41

\_\_\_\_\_\_\_\_\_\_ syndrome is a disorder of bone marrow stem cells in which the cells do not normally differentiate into mature cells.

Answer 41

**_Myelodysplastic_** syndrome is a disorder of bone marrow stem cells in which the cells do not normally differentiate into mature cells.

Question 42

What syndrome is characterized by defective stem cell maturation in the bone marrow and an increased risk of AML development?

Answer 42

Myelodysplastic syndrome

Question 43

\_\_\_\_\_\_\_\_\_\_\_ myelodysplastic syndrome follows such things as chemotherapy (especially alkylating agents), radiation exposure, benzene exposure, or Fanconi anemia.

Answer 43

**_Secondary_** myelodysplastic syndrome follows such things as chemotherapy (especially alkylating agents), radiation exposure, benzene exposure, or Fanconi anemia.

Question 44

What is the median age for diagnosis with myelodysplastic syndrome?

Answer 44

**70** years

Question 45

Most cases of myelodysplastic syndrome are __________ but shorten the affected patient's life in the long-run via an increase in risk of infection, bleeding, and AML.

Answer 45

Most cases of myelodysplastic syndrome are **_asymptomatic_** but shorten the affected patient's life in the long-run via an increase in risk of infection, bleeding, and AML.

Question 46

The bone marrow in myelodysplastic syndrome is usually \_\_\_\_\_\_cellular; but, due to changes in hematopoiesis, the cell counts are __________ in the peripheral blood.

Answer 46

The bone marrow in myelodysplastic syndrome is usually **_hyper_**cellular; but, due to changes in hematopoiesis, the cell counts are **_decreased_** in the peripheral blood.

Question 47

A 73 year old male presents with a megaloblastic anemia refractory to B12 and/or folate administration. Orotic acid levels are normal. Analysis of the bone marrow shows ringed sideroblasts and no increase in blasts. What is the likely diagnosis?

Answer 47

**Myelodysplastic** **syndrome** (specifically, refractory anemia with ringed sideroblasts (**RARS**))

Question 48

A 73 year old male presents with a megaloblastic anemia refractory to B12 and/or folate administration. Orotic acid levels are normal. Analysis of the bone marrow shows ringed sideroblasts and an increase in blasts. You diagnose the patient with myelodysplastic syndrome (specifically, refractory anemia with elevated blasts (RAEB)). **Does this patient have an increased risk of AML development?**

Answer 48

**Yes** (high-risk group).

Question 49

What is the most common chromosomal abnormality seen in myelodsyplastic syndrome?

Answer 49

**Trisomy 8** | (also, monosomies of 5 or 7)

Question 50

How is myelodysplastic syndrome typically treated?

Answer 50

Supportive care | (antibiotics and blood transfusions)

Question 51

**Myelodysplastic syndrome** is characterized by \_\_\_\_\_\_cellular bone marrow that produce _______ cells. **Aplastic anemia** is characterized by \_\_\_\_\_\_cellular bone marrow that produce _______ cells.

Answer 51

**Myelodysplastic syndrome** is characterized by **_hyper_**cellular bone marrow that produce **_defective_** cells. **Aplastic anemia** is characterized by **_hypo_**cellular bone marrow that produce **_normal_** (*albeit very few*) cells.

Question 52

\_\_\_\_\_\_\_\_ **syndrome** is characterized by **hyper**cellular bone marrow that produce **defective** cells. \_\_\_\_\_\_\_\_ **anemia** is characterized by **hypo**cellular bone marrow that produce **normal** (*albeit very few*) cells.

Answer 52

**_Myelodysplastic_ syndrome** is characterized by **hyper**cellular bone marrow that produce **defective** cells. **_Aplastic_ anemia** is characterized by **hypo**cellular bone marrow that produce **normal** (*albeit very few*) cells.

Question 53

What **myeloproliferative** disorder mainly leads to an increase in **erythrocytes**?

Answer 53

Polycythemia vera

Question 54

What **myeloproliferative** disorder mainly leads to an increase in **platelets**?

Answer 54

Essential thrombocytosis

Question 55

What **myeloproliferative** disorder mainly leads to an increase in **granulocytes**?

Answer 55

CML

Question 56

What myeloproliferative disorder mainly leads to an increase in fibrous tissue?

Answer 56

Myeloid metaplasia

Question 57

# The following myeloproliferative disorder typically leads to an increase in what cell type in particular? **Polycythemia vera**

Answer 57

Erythrocytes

Question 58

# The following myeloproliferative disorder typically leads to an increase in what cell type in particular? **Essential thrombocytosis**

Answer 58

Platelets

Question 59

# The following myeloproliferative disorder typically leads to an increase in what cell type in particular? **Chronic myelogenous leukemia**

Answer 59

Granulocytes

Question 60

# The following myeloproliferative disorder typically leads to an increase in what substance/cell/tissue/product in particular? **Myeloid metaplasia**

Answer 60

Fibrous tissue

Question 61

About \_\_\_\_% of patients with polycythemia vera are asymptomatic and the disorder is diagnosed by routine blood counts.

Answer 61

About **_70_**% of patients with polycythemia vera are asymptomatic and the disorder is diagnosed by routine blood counts.

Question 62

Secondary polycythemia vera results from what example causes?

Answer 62

Tumors, hypoxia, hemoglobinopathies, etc.

Question 63

**True/False**. Most patients with polycythemia vera have a shortened life expectancy, with bleeding being the most common cause of death.

Answer 63

**False**. Most patients with polycythemia vera have a ***normal*** life expectancy, with ***thrombosis*** being the most common cause of death.

Question 64

A 65 year old man presents with headache, bleeding, and thrombosis. Upon examination, you note splenomegaly and pruritis. The man's hemoglobin, hematocrit, and RBC size are all highly elevated, with some elevation in neutrophil and platelet counts. **What gene is likely mutated** **in this man?**

Answer 64

***JAK2*** | (polycythemia vera)

Question 65

How is polycythemia vera treated?

Answer 65

**RBC reduction** (e.g. via phlebotomy, chemotherapy, etc.)

Question 66

Essential thrombocytosis is characterized by excessive proliferation of ___________ and increased numbers of circulating platelets.

Answer 66

Essential thrombocytosis is characterized by excessive proliferation of **_megakaryocytes_** and increased numbers of circulating platelets.

Question 67

**True/False**. Platelet counts in essential thrombocytosis can get as high as **1 million** / mm³!

Answer 67

True.

Question 68

The major complications of essential thrombocytosis are those related to either ________ or \_\_\_\_\_\_\_\_.

Answer 68

The major complications of essential thrombocytosis are those related to either **_thrombosis_** (*due to hugely increased platelet count*) or **_bleeding_** (*due to defective nature of produced platelets*).

Question 69

How is essential thrombocytosis treated?

Answer 69

**Platelet count reduction** (e.g. cytoreductive therapy, platelet pheresis, etc.)

Question 70

CML is characterized by extreme blood \_\_\_\_\_\_\_cytosis, \_\_\_\_philia, and \_\_\_\_\_\_\_megaly.

Answer 70

CML is characterized by extreme blood **_granulo_**cytosis, **_baso_**philia, and **_spleno_**megaly.

Question 71

CML usually results due to what mutation?

Answer 71

t(**9**;**22**) | (the Philadelphia chromosome)

Question 72

The t(9;22) seen in CML results in synthesis of what fusion product?

Answer 72

BCR-ABL

Question 73

Patients with CML may be asymptomatic or may present with symptoms due to ________________ (high WBC count impedes intravascular flow in the brain, lungs, or heart --- include dizziness, delirium, shortness of breath, or blurred vision or slurred speech).

Answer 73

Patients with CML may be asymptomatic or may present with symptoms due to **_hyperleukocytosis_** (high WBC count impedes intravascular flow in the brain, lungs, or heart --- include dizziness, delirium, shortness of breath, or blurred vision or slurred speech).

Question 74

**Hyperleukocytosis** (high WBC count impeding intravascular flow in the brain, lungs, or heart --- leads to dizziness, delirium, shortness of breath, or blurred vision or slurred speech) is associated with what **malignancy**?

Answer 74

CML (typically occurs when counts are ~**300,000 - 800,000**)

Question 75

**True/False**. CML typically occurs after the 4th decade of life.

Answer 75

True.

Question 76

Arrange the following phases of CML in typical order of occurrence: **Accelerated** phase **Blast** **crisis** **Chronic** phase

Answer 76

1. **Chronic** phase 2. **Accelerated** phase 3. **Blast crisis** (culminates in acute leukemia)

Question 77

**True/False**. AML often results in a culminating CML.

Answer 77

**False**. ***CML*** often results in a culminating **blast** **crisis** **/** ***acute leukemia***.

Question 78

**True/False**. Once CML patients enter the blast crisis phase, they usually die from acute leukemia.

Answer 78

True.

Question 79

The CML progression occurs over ___ - ___ years. Treatment of CML is directed at initial **symptoms** and reduction of the **WBC** count. CML is potentially curable with ______________ performed before the blast crisis.

Answer 79

The CML progression occurs over **_3_** - **_5_** years. Treatment of CML is directed at initial **symptoms** and reduction of the **WBC** count. CML is potentially curable with **_bone marrow transplantation_** performed before the blast crisis.

Question 80

Myeloid metaplasia is characterized by ________ of the bone marrow and a resulting increase in _________ hematopoeisis.

Answer 80

Myeloid metaplasia is characterized by **_fibrosis_** of the bone marrow and a resulting increase in **_extramedullary_** hematopoeisis.

Question 81

**True/False**. Myeloid metaplasia is a disorder of progressively fibrotic bone marrow associated with hepatomegaly, a lack of immature cells in the peripheral blood, and echinocytes due to increased intramedullary hematopoeisis.

Answer 81

**False**. Myeloid metaplasia is a disorder of progressively fibrotic bone marrow associated with ***spleno***megaly, an ***increase*** in immature cells in the peripheral blood, and ***dacro***cytes due to increased ***extra***medullary hematopoeisis.

Question 82

**True/False**. Treatment options for myeloid metaplasia include _chemotherapy, interferon therapy and splenectomy_. The major causes of death are _infection, hemorrhage_ and (rarely) the development of _acute leukemia_.

Answer 82

True.

Question 83

What are the main symptoms of splenomegaly?

Answer 83

Early satiety, left side abdominal pain

Question 84

Mastocytosis is associated with what mutation?

Answer 84

*KIT*

Question 85

What feature is most important in differentiating a malignant from a benign tumor? A. Size B. Mitotic rate C. Metastasis D. Necrosis

Answer 85

C. Metastasis

Question 86

Cancers that commonly occur in tissues that have gone through the sequence of metaplasia - dysplasia - malignancy include all except: A. Squamous cell carcinoma of cervix B. Squamous cell carcinoma of bladder C. Squamous cell carcinoma of lung D. Squamous cell carcinoma of esophagus

Answer 86

D. Squamous cell carcinoma of esophagus

Question 87

A 65-year-old hypertensive man presented complaining of right costovertebral angle pain and gross hematuria. On physical examination a mass was palpated in the right flank. During the work-up for these problems, a solitary lesion was found in his right lung. Subsequently he had a trivial accident and fractured his right femur. Can you tie together the seemingly disparate findings in this case? A. Metastatic cancer B. Adenomas C. Neuroendocrine tumor D. Hamartomas

Answer 87

A. Metastatic cancer

Question 88

A 79-year-old man was admitted to the hospital with complaint of suprapubic pain associated with hematuria. Workup for hematuria was pursued. Urine analysis showed numerous red blood cells, many neutrophils, and bacteria. Urine cytology showed hyperchromatic neoplastic cells consistent with transitional cell carcinoma. Subsequent bladder biopsy showed a high-grade transitional cell carcinoma. All of the following statements about the above neoplasm are correct except: A. It has been associated with p53 gene mutation. B. It arises only in the bladder. C. It is regarded as clonal in nature D. It has been etiologically associated with cigarette smoking.

Answer 88

B. It arises only in the bladder.

Question 89

The process of grading and staging of cancer is an attempt to estimate the aggressiveness or degree of malignancy of a cancer. Which one of the following statements is correct? A. Grading of cancer has greater clinical value. B. Staging is based on the cytologic differentiation of tumor cells and the number of mitoses within the tumor. C. Staging is based on the size of the primary lesion, its extent of spread to regional lymph nodes, and the presence or absence of metastases. D. Grading is based on the degree of local invasion of the primary tumor.

Answer 89

C. Staging is based on the size of the primary lesion, its extent of spread to regional lymph nodes, and the presence or absence of metastases.

Question 90

All of the following oncogenic viruses are correctly paired with associated tumors except: A. HTLV-1 -- Adult T cell leukemia/lymphoma B. Hepatitis C virus (HCV) -- hepatocellular carcinoma C. Human papilloma virus -- laryngeal papillomas D. Epstein-Barr virus -- carcinoma of cervix.

Answer 90

D. Epstein-Barr virus -- carcinoma of cervix.

Question 91

A 22-year-old woman went for a routine visit to her gynecologist, who identified a well delimited mass in her right ovary. The left ovary felt enlarged, but did not show signs of a discrete mass. X-ray and cat scan were done to confirm the abnormality in the right ovary. The tumor was excised and grossly it was cystic and filled with greasy tan, viscous jelly-like material containing hair. This tumor is best classified as: A. Teratoma (dermoid) B. Mixed tumor C. Carcinoma D. Sarcoma

Answer 91

A. Teratoma (dermoid)

Question 92

A 62-year-old man complained of headaches for the past 5-6 months. Lately, the pain had become intolerable. He was vomiting frequently and complained of decreased visual acuity. Physical exam revealed the presence of papilledema. Following an MRI scan, which revealed a "butterfly" cerebral mass, craniotomy was preformed. The tissue was represented by irregularly arranged atypical glial cells, which had markedly pleomorphic, hyperchromatic nuclei. Multi-lobulated nuclei with coarse irregular chromatin were also present along with prominent mitotic activity. There was palisading necrosis with angioplasia present. Based on the location, history, radiographic features and histology, this tumor is best represented as: A. Malignant brain tumor (glioblastoma multiforme) B. Benign C. Metastatic carcinoma D. Infarction E. Low-grade glioma

Answer 92

A. Malignant brain tumor (glioblastoma multiforme)

Question 93

This 75-year-old man went for a routine medical check-up. On digital rectal examination (DRE), an unusually hard nodule was palpated in the prostate gland. Blood was drawn in a red top tube, and serum sent for prostatic-specific antigen (PSA) showed a value of 80 ng/ml (expected, 0.1-4.0 ng/ml). A biopsy was performed, followed by suprapubic prostatectomy. Which one of the following statements is not true? A. Prostate specific antigen is a tumor marker commonly used to screen for prostate cancer. B. The three most common cancers in men are prostate, lung and colorectum C. There is 20% greater prevalence of cancer in African Americans. D. Cancers that are decreasing in incidence are lung, breast, and prostate. E. Risk factor for cancer include smoking, high fat, low fiber diet, and obesity.

Answer 93

D. Cancers that are decreasing in incidence are lung, breast, and prostate.

Question 94

A 41-year-old woman has a peripheral blood WBC count of 182,800/µL, with mature and immature myeloid cells predominating. Cytogenetic analysis of cells obtained through bone marrow aspiration reveals a t(9;22) translocation. This has resulted in formation of a hybrid gene, resulting in increased tyrosine kinase activity. Which one of the following genes was translocated from chromosome 9? A. p53 B. Rb C. c-abl D. K-ras E. NF-1

Answer 94

C. c-abl

Question 95

A rectal polyp is found by colonoscopy of a 58-year-old woman. The excised polyp histologically reveals well-differentiated glands with no stalk invasion. Which one of the following investigational research procedures best distinguishes whether the polyp represents hyperplasia of the colonic mucosa or a tubular adenoma (adenomatous polyp)? A. Determination of clonality by pattern of X chromosome inactivation B. Immunoperoxidase staining for cytokeratin (AE1/AE3) C. Histochemical staining for neutral mucin D. Flow cytometry to determine the percentage of cells in the S phase (growth fraction) E. Immunoperoxidase staining for factor VIII and CD31

Answer 95

A. Determination of clonality by pattern of X chromosome inactivation

Question 96

At birth, a child has a single functional copy of a tumor suppressor gene. At the age of 8 years, the remaining normal allele is lost through a mutation. As a result, the ability to control the transition from G1 to the S phase of cell cycle is lost. Which one of the following neoplasms is most likely to arise by this mechanism? A. Adenocarcinoma of colon B. Ductal carcinoma of breast C. Retinoblastoma D. Cerebral glioblastoma multiforme E. Chronic myeloid leukemia

Answer 96

C. Retinoblastoma

Question 97

An immunoperoxidase stain for the protease cathepsin D is performed on tissue from a ductal breast carcinoma in a 69-year-old woman. There is pronounced cytoplasmic expression in the tumor cells by prominent staining. The presence of this marker is most likely to predict tumor: A. Differentiation B. Aneuploidy C. Angiogenesis D. Heterogeneity E. Invasiveness

Answer 97

E. Invasiveness

Question 98

A 62-year-old woman has a granulosa-theca cell tumor of her right ovary that produces estrogen. She subsequently develops endometrial carcinoma. The coexistence of these two tumors is an example of which one of the following? A. Genetic susceptibility to tumorigenesis B. A paraneoplastic syndrome C. Tumor de-differentiation D. Promotion of carcinogenesis E. Mutation of a tumor suppressor gene F. Tumor heterogeneity

Answer 98

D. Promotion of carcinogenesis

Question 99

A 29-year-old woman presents for her yearly gynecologic examination. A cervical Pap smear is obtained revealing “koilocytic atypia” characterized by perinuclear halos hyperchromasia and wrinkled nuclei. A cervical biopsy reveals invasive moderately differential squamous cell carcinoma. Molecular tests for human papillomavirus (HPV) reveals positive tumor cells. Which one of the following mechanisms of disease best explains the role of HPV in the pathogenesis of this patient’s neoplastic condition? A. Episomal viral replication B. Insertional mutagenesis C. Activation of cellular oncogenes D. Inactivation of tumor suppressor proteins E. Enhanced transcription of telomerase gene

Answer 99

D. Inactivation of tumor suppressor proteins

Question 100

A 65-year-old woman presents with a 4-month history of increasing weight loss, and shortness of breath. She has smoked three packs of cigarettes a day for 40 years. Her past medical history is significant for emphysema and chronic bronchitis. A chest x-ray shows a 6-cm mass in her right lung. Bronchoscopy discloses obstruction of the right main stem bronchus. A biopsy reveals squamous cell carcinoma. Immunohistochemical studies of this biopsy specimen would most likely show strong expression of which one of the following tumor markers? A. Cytokeratins B. Synaptophysin C. CDX-2 D. Alpha-fetoprotein E. Calretinin

Answer 100

A. Cytokeratins

Question 101

A patient with cervical carcinoma undergoes a hysterectomy. In addition to a focus of deeply invasive carcinoma, the pathologist identifies dysplastic squamous cells occupying the entire thickness of the cervical epithelium, with no evidence of maturation. The basement membrane in these areas appears intact. Which one of the following terms best describes this cervical lesion? A. Carcinomatosis B. Carcinoma in situ C. Atypical hyperplasia D. Complex hyperplasia E. Microinvasive carcinoma

Answer 101

B. Carcinoma in situ

Question 102

A 38-year-old man presents with a 6-month history of multiple reddish nodules on his foot. Biopsy of the nodule discloses a poorly demarcated lesion composed of fibroblasts and atypical endothelial-like cells lining vascular spaces. Further work-up identifies similar lesions in the lymph nodes and liver. The neoplastic cells contain sequences of human herpesvirus-8 (HHV-8). This patient most likely has which one of the following diseases? A. Neurofibromatosis type I B. Xeroderma pigmentosum C. Li-Fraumeni syndrome D. Acquired immunodeficiency E. Ataxia telangiectasia

Answer 102

D. Acquired immunodeficiency

Question 103

A 62-year-old woman presents with increasing pigmentation of the skin. Physical examination shows hyperkeratosis and hyperpigmentation of the axilla, neck, flexures, and anogenital region. Endocrinologic studies reveal normal serum levels of adrenal corticosteroids, glucocorticoids, TSH, and PTH levels. If this patient's skin pigmentation represents a paraneoplastic syndrome, the primary tumor would most likely be found in which of the following anatomic locations? A. Pleura B. Cervix C. Stomach D. Bladder E. Esophagus

Answer 103

C. Stomach

Question 104

A 59-year-old woman presents with a 2-year history of upper truncal obesity and moderate depression. Physical examination shows hirsutism and moon facies. A CT scan of the thorax displays a hilar mass bilateral adrenal masses and multiple enlarged peri-aortic lymph nodes. A transbronchial lung biopsy reveals small-cell carcinoma. Electron microscopy of this tumor will most likely reveal which one of the following morphologic features? A. Hyperplasia of rough endoplasmic reticulum B. Hyperplasia of smooth endoplasmic reticulum C. Mitochondrial calcification D. Neuroendocrine granules E. Myelin figures in lysosomes

Answer 104

D. Neuroendocrine granules

Question 105

A 59-year-old woman presents with a 2-year history of upper truncal obesity and moderate depression. Physical examination shows hirsutism and moon facies. A CT scan of the thorax displays a hilar mass bilateral adrenal masses and multiple enlarged peri-aortic lymph nodes. A transbronchial lung biopsy reveals **small-cell carcinoma**. What antigens would the tumor cells most likely express immunohistochemically? A. S-100, HMB-45, Melan-A B. Cytokeratin, neuron specific enolase, chromograin, synaptophysin C. Calretinin, cytokeratin D. Cytokeratin, CA-125, EMA E. EMA, CA 19.9, CEA F. LCA, CD-20, CD79a G. CD-31, CD-34, Factor VIII associated Antigen H. Vimentin, Desmin, Muscle specific actin I. LCA, CD-3

Answer 105

B. Cytokeratin, neuron specific enolase, chromograin, synaptophysin

Question 106

A 45-year-old man presents with increase urinary frequency and dribbling. He is found to have a bladder mass. At biopsy, a tumor containing high-grade cytologically malignant epithelioid cells and spindle cells is found. Both epithelioid and spindle cells express cytokeratin (AE1/AE3, and CAM 5.2) by immunoperoxidase stains. Tumor cells do not express vimentin, calretinin, desmin, muscle specific actin, CEA, prostate specific antigen, TTF-1 or myoglobin by immunoperoxidase stains. Which one of the following is the most likely diagnosis? A. Metastatic pulmonary carcinosarcoma B. Primary spindle cell carcinoma of bladder C. Malignant mesothelioma involving bladder D. Metastatic prostatic carcinoma E. Primary leiomyosarcoma of bladder F. Primary rhabdomyosarcoma of bladder G. Sarcoma, not further classified

Answer 106

B. Primary spindle cell carcinoma of bladder

Question 107

A 61-year-old woman presents with hypochromic microcytic anemia and jaundice. A CT scan reveals a large (8.5 cm) hepatic mass. A liver biopsy reveals high-grade cytologically malignant epithelioid cells forming nests separated by desmoplastic stroma. The tumor cells express cytokeratin (AE1/AE3), CEA and CDX-2 by immunohistochemical stains. Tumor cells do not express TTF-1, alpha-fetoprotein, CA19.9, CD117, CA125, muscle actin, desmin, or vimentin with immunoperoxidase stains. **Which of the following is the most likely diagnosis?** A. Metastatic lung carcinoma B. Metastatic leiomyosarcoma C. Primary hepatocellular carcinoma D. Metastatic pancreatic carcinoma E. Metastatic colon carcinoma F. Primary cholangiocarcinoma G. Metastatic gastrointestinal stromal tumor (GIST) H. Metastatic ovarian carcinoma

Answer 107

E. Metastatic colon carcinoma

Question 108

A 48-year-old alcoholic man with a 40 pack-year history of cigarette smoking presents with a 30 lb weight loss over the past 3 months and hemoptysis. Physical exam reveals leukoplakia of oral cavity with a 0.3 cm ulcer of the tongue. A CXR reveals a single right pulmonary-hilar mass. The lung mass is biopsied and reveals a high-grade “small blue cell neoplasm” with marked mitotic activity. Tumor cells express cytokeratin (AE1/AE3, and CAM5.2), TTF-1, neuron specific enolase (NSE), chromogranin, and synaptophysin by immunohistochemical stain. Tumor cells do not express S-100, HMB-45, LCA, muscle actin, myogenin and myoglobin with immunoperoxidase stains. **Which one of the following is the most likely diagnosis of this patient?** A. Pulmonary carcinoid tumor B. Pulmonary small cell carcinoma (neuroendocrine differentiation) C. Lymphoma D. Metastatic melanoma E. Embryonal rhabdomyosarcoma F. Squamous cell carcinoma G. Metastic follicular carcinoma of thyroid

Answer 108

B. Pulmonary small cell carcinoma (neuroendocrine differentiation)

Question 109

A 33-year-old woman presents with a large soft tissue mass of her right thigh. The mass is biopsied producing a bloody field. The biopsy reveals cytologically malignant spindle cells creating cavernous spaces filled with erythrocytes. Some spindle cells bridge across the spaces. The spindle cells express vimentin, CD31, CD34, and Factor VIII associated antigen by immunoperoxidase stains. Tumor cells do not express cytokeratin, desmin, muscle specific actin, S-100, melan-A, HMB-45, or LCA (leukocyte common antigen) by immunohistochemical stain. **Which one of the following is the most likely diagnosis?** A. Spindle cell carcinoma B. Malignant melanoma C. Malignant nerve sheath tumor (malignant Schwannoma) D. B-cell lymphoma E. Leiomyosarcoma F. Rhabdomyosarcoma G. Angiosarcoma H. T-cell lymphoma

Answer 109

G. Angiosarcoma

Question 110

A 42-year-old woman presents with fatigue, 15 lb. weight loss over the previous 4 months, and a soft tissue mass of her left lower back. Physical exam reveals multiple small non-tender pea-size firm cervical and axillary lymph nodes. Present in the left lower back is a 4.5 cm firm non-tender soft tissue mass. A CBC reveals a Hgb of 9 gms and hematocrit of 27% with normal indices. Tear-drop shaped erythrocytes and a single nucleated RBC and single myelocyte are found in the peripheral smear. Platelets are present in adequate numbers with increased large forms. A biopsy of the left lower back mass reveals a malignant “small blue cell neoplasm”. Tumor cells express vimentin, LCA, CD20, and CD79a. Tumor cells do not express CD3, UCHL-1, synaptophysin, chromogranin, NSE, cytokeratin, epithelial membrane antigen (EMA), muscle actin, myoglobin, myogenin, S-100, CD31, or HMB-45. **Which one of the following is the most likely diagnosis?** A. B-cell lymphoma B. Small cell carcinoma C. Malignant melanoma D. Rhabdomyosarcoma E. Angiosarcoma F. Clear cell carcinoma G. T-cell lymphoma H. Large cell undifferentiated carcinoma I. Sarcoma, not further classified

Answer 110

A. B-cell lymphoma

Question 111

Which of the following is the most likely diagnosis? 1. Hairy cell leukemia 2. CLL/SLL 3. CML 4. Acute leukemia 5. Infectious mononucleosis

Answer 111

Which of the following is the most likely diagnosis? 1. **Hairy cell leukemia** 2. CLL/SLL 3. CML 4. Acute leukemia 5. Infectious mononucleosis

Question 112

What do you expect to see on bone marrow aspirate?

Answer 112

**Dry tap**

Question 113

What is the most likely diagnosis?

Answer 113

**CML** (granulocytosis, basophilia, splenomegaly)

Question 114

What is the molecular/cytogenetic abnormality in these cells?

Answer 114

**t(9;22)**(q34;q11) **BCR-ABL**1

Question 115

Which of the following is the most likely diagnosis? 1. CML 2. Acute leukemia 3. Hairy cell leukemia 4. CLL/SLL 5. Infectious mononucleosis

Answer 115

Which of the following is the most likely diagnosis? 1. CML 2. Acute leukemia 3. Hairy cell leukemia 4. **CLL/SLL (smudge cells shown above)** 5. Infectious mononucleosis

Question 116

Which of the following is a possible complication of this disorder? 1. Serum hyperviscosity 2. Blast crisis 3. Bone marrow fibrosis 4. Tumor lysis syndrome 5. Development of autoimmune hemolytic anemia

Answer 116

Which of the following is a possible complication of this disorder? 1. Serum hyperviscosity 2. Blast crisis 3. Bone marrow fibrosis 4. Tumor lysis syndrome 5. **Development of autoimmune hemolytic anemia**

Question 117

Which of the following is the most likely diagnosis? 1. CLL 2. Acute leukemia 3. Hairy cell leukemia 4. CLL/SLL 5. Infectious mononucleosis

Answer 117

Which of the following is the most likely diagnosis? 1. CLL 2. **Acute leukemia** 3. Hairy cell leukemia 4. CLL/SLL 5. Infectious mononucleosis

Question 118

This patient later presents with DIC and is found to have a balanced translocation involving chromosomes 15 and 17. Which of the following is an effective therapy for this disorder? 1. 5-fluorouracil 2. Prednisone 3. All-trans retinoic acid 4. Fludarabine 5. Imatinib

Answer 118

This patient later presents with DIC and is found to have a balanced translocation involving chromosomes 15 and 17. Which of the following is an effective therapy for this disorder? 1. 5-fluorouracil 2. Prednisone 3. **All-trans retinoic acid** 4. Fludarabine 5. Imatinib

Question 119

Which of the following is the most likely diagnosis? 1. Myelodysplastic syndrome 2. CLL/SLL 3. CML 4. Acute leukemia 5. Hairy cell leukemia

Answer 119

Which of the following is the most likely diagnosis? 1. **Myelodysplastic syndrome (Pseudo Pelger Huet cells --- ‘dumbbell’ neutrophils)** 2. CLL/SLL 3. CML 4. Acute leukemia 5. Hairy cell leukemia

Question 120

What is the LEAST likely finding in this patient’s peripheral blood and/or bone marrow? 1. Pancytopenia 2. Leukocytosis 3. Hypercellular bone marrow 4. 7% blasts in the bone marrow 5. Complex cytogenetic abnormalities

Answer 120

What is the LEAST likely finding in this patient’s peripheral blood and/or bone marrow? 1. Pancytopenia 2. **Leukocytosis (not common in myelodysplastic syndrome)** 3. Hypercellular bone marrow 4. 7% blasts in the bone marrow 5. Complex cytogenetic abnormalities

Question 121

1. Follicular lymphoma 2. CLL/SLL 3. AML 4. ALL 5. Infectious mononucleosis

Answer 121

1. Follicular lymphoma 2. CLL/SLL 3. AML 4. **ALL** 5. Infectious mononucleosis

Question 122

Answer 122

B. (check for infectious mononucleosis FIRST --- bone marrow biopsy is invasive/painful/expensive)

Question 123

A. Bernard-Soulier syndrome B. Acute promyelocytic leukemia C. von Willebrand disease D. Hemophilia B E. ITP

Answer 123

1. Bernard-Soulier syndrome (the image shows giant platelets)

Question 124

Answer 124

D.

Question 125

Answer 125

D.

Question 126

Answer 126

B. (Auer rod in myeloblast)

Question 127

Answer 127

A. (follicular pattern)

Question 128

For a follicular lymphoma....

Answer 128

A.

Question 129

The CEA marker is most strongly associated with tumors from what location?

Answer 129

The GI tract

Question 130

**True/False**. Iron deficiency is associated with adenocarcinoma.

Answer 130

True.

Question 131

While both are easily larger than a RBC, which is _much_ larger? Hairy cells in HCL Blasts

Answer 131

Blasts

Question 132

**True/False**. Alpha-fetoprotein is associated with certain pancreatic malignancies.

Answer 132

True.

Question 133

TTF-1 is a sensitive marker for what malignancies?

Answer 133

Pulmonary and thyroid adenocarcinomas