Hem n Onc 8-7 (8)

Question 1

This patient presents with excessive bleeding from the nose and gums along with small, pinpoint areas of bleeding within the skin (petechiae). He is tired and has lost a significant amount of weight. His lab tests show elevated prothrombin time (PT), bleeding time (BT), and partial thromboplastin time (PPT) and decreased fibrinogen. Taken together, these clues suggest that the patient is experiencing?

Answer 1

disseminated intravascular coagulation (DIC). DIC is characterized by significant abnormalities in coagulation and can clinically manifest with both excess bleeding and thrombosis.

Question 2

The findings of leukemia plus DIC are most commonly associated with APL, a variant of AML. The characteristic chromosomal translocation of?

Answer 2

AML is t(15;17).

Question 3

The t(8;14) translocation is characteristic of Burkitt lymphoma, which manifests most commonly as an isolated enlarging mass.
The t(9;22) translocation, also known as the Philadelphia chromosome, is associated with chronic myelogenous leukemia.
The t(11;14) translocation is characteristic of ?

Answer 3

mantle cell lymphoma.
The t(12;21) translocation is commonly seen in acute lymphoblastic leukemia.

Question 4

This patient’s combination of “B”-symptoms (fever, weight loss, fatigue) and a hard neck mass with a t([14;18]) translocation is diagnostic for follicular lymphoma. The chromosomal translocation (t[14;18]) results in upregulation of the antiapoptotic factor Bcl-2. Bcl-2, along with Bcl-xL, prevents the release of cytochrome c and stops it from binding to APAF-1 and activating the caspase cascade, which results in apoptosis. In B-lymphocyte malignancies, particularly follicular lymphoma, upregulation of bcl-2 resulting from a?

Answer 4

chromosomal translocation (t[14;18]) then acts to confer a survival benefit to otherwise dying cells and promotes malignant transformation.

Question 5

he translocation t(14;18) causes increased activity of Bcl-2, an?

Answer 5

antagonist of apoptotic cell death, making a patient more susceptible to follicular lymphoma and other B-lymphocyte malignancies.

Question 6

Upregulation of the cell cycle results from inappropriate activation of the protein coded by c-Myc, a transcription factor that drives cell proliferation.
TP53 is a cell cycle inhibitor in response to the detection of a DNA error. If repair is not possible, the gene p53 then initiates apoptosis. A mutation in p53 is found in numerous cancers, including colon cancer and B-lymphocyte lymphoma.
Agonism of apoptosis is carried out by BAX, BAK, and other proapoptotic proteins. When repair of DNA is not possible, these proteins allow the release of caspase-activating proteins from the mitochondria to trigger cell death.
Constitutive activation of G proteins, such as the RAS protein, is seen in many cancers. Activation of RAS is seen in?

Answer 6

neurofibromatosis.
Inactivation of p53 occurs in a number of cancers. p53 functions as a tumor suppressor gene, so loss of p53 confers a cellular state that supports progression to malignancy.

Question 7

This patient’s history of painful episodes requiring hospitalization should raise suspicion for sickle cell disease. Patients with sickle cell disease tend to present at a young age with painful vaso-occlusive crises, which occur when sickled RBCs occlude capillaries and restrict blood flow. Autosplenectomy typically occurs in sickle cell patients by this patient’s age as a result of repeated splenic infarcts. Patients with impaired splenic function are susceptible to infection by encapsulated organisms such as Salmonella typhi. This is because the spleen is rich in macrophages that can recognize and clear complement- or IgG-coated sugar-rich capsules. The symptoms suggest that the boy has?

Answer 7

osteomyelitis of the tibia, and the most important determinant of virulence in sickle cell patients with osteomyelitis is the presence of a bacterial capsule. Staphylococcus aureus is the most common cause of osteomyelitis in all groups, but Salmonella osteomyelitis has a particular association with sickle cell disease, and it is this association that is often tested on the Step 1 USMLE.

Question 8

While bacterial pili do allow cells to adhere to surfaces in hosts, they are not a virulence factor allowing Salmonella to cause osteomyelitis.
Mycolic acids are components of the outer mycobacterial membrane and are not found in Salmonella capsules.
Flagella allows for motility but does not explain?

Answer 8

the enhanced virulence of Salmonella in sickle cell disease.

Mycoplasma species do not have a cell wall, but this does not contribute to enhanced virulence in sickle cell patients.

Question 9

The patient presents with weight loss, signs of anemia, generalized lymphadenopathy, and hepatosplenomegaly, which strongly suggests a non-Hodgkin lymphoma. Systemic symptoms of Hodgkin lymphoma may include “B” symptoms, such as fever, weight loss, and drenching night sweats. These symptoms—which can be seen in both Hodgkin and non-Hodgkin lymphoma—are observed in approximately 40% of patients with non-Hodgkin lymphoma and are a poor prognostic indicator. Non-Hodgkin lymphoma often involves ?

Answer 9

multiple lymph nodes, while extranodal involvement is also common. One risk factor for non-Hodgkin lymphoma is immunosuppression.
Neoplastic B lymphocytes are the cells of origin in most non-Hodgkin lymphomas (90% of cases). The subtypes of non-Hodgkin lymphomas include Burkitt lymphoma, mantle cell lymphoma, follicular lymphoma, diffuse large B-cell lymphoma, and marginal zone lymphoma. Approximately 10% of lymphomas are Hodgkin lymphomas.

Question 10

Acute myelogenous and promyelocytic leukemia feature increases in myeloblasts. Acute promyelocytic leukemia is caused by a t(15;17) mutation and features symptoms of marrow failure, such as anemia and thrombocytopenia, along with splenomegaly and bleeding from the gums.
Plasma cells are mutated and overactive in multiple myeloma, which can present with hypercalcemia, generalized weakness, and renal failure.

Reed-Sternberg cells are CD15 and CD30 positive neoplastic cells in Hodgkin lymphoma, which can present with?

Answer 10

fever, night sweats, and localized lymphadenopathy, unlike the generalized lymphadenopathy of non-Hodgkin lymphoma.

T-cell lymphomas such as Sézary syndrome and T-cell lymphoblastic leukemia can present with a mediastinal mass.

Question 11

The prevalence is the number of individuals with a disease in a given population at risk for that particular disease at a given time. Prevalence can be estimated in cross-sectional studies, in which the disease (breast mass) is compared with an exposure (history of estrogen therapy). In the chart, the prevalence can be determined by calculating the number of patients with a breast mass (W + Y) divided by ?

Answer 11

the total number of people in the population (W + X + Y + Z), or (W + Y)/(W + X + Y + Z).

Question 12

(W + X) / (W + X + Y + Z) is the proportion of the population who are exposed to hormone therapy.
W/(W +Y) is a proportion of breast cancer patients who are exposed to hormone therapy.
Z/(Z + X) s the proportion of patients with no breast mass that also had not been exposed to hormone therapy.
W/(W + X) is the?

Answer 12

proportion of those exposed to hormone therapy who have a breast mass.

Question 13

Among both sexes, lung cancer is by far the leading cause of cancer mortality (33% of cancer deaths for men and 23% for women). Adenocarcinoma, characterized by glandular differentiation and frequently stains mucin positive (shown in the image), is ?

Answer 13

a common type of lung cancer. It is the most common type of lung cancer in women.

Question 14

Adenomatous lesions invading the submucosa and muscularis propria describe colorectal cancer, the third leading cause of cancer-related deaths in the United States among both men and women.
In women, breast cancer is the leading cause of cancer and the second most common cause of cancer deaths. Breast cancer includes ductal carcinoma in situ, which presents as?

Answer 14

malignant cells limited to ducts and lobules. Cyst with microscopic papillae and psammoma bodies describe serous ovarian carcinoma, and ovarian cancers represent the fifth leading cause of cancer deaths in women.

Lastly, HPV infection of the cervix can lead to koilocytotic atypia, which would predispose to cervical cancer, which is not a leading cause of cancer mortality in women. Deaths from cervical cancer have dramatically fallen since screening by Papanicolaou smear was introduced.

Question 15

This patient presents with a scaling, indurated, ulcerated nodule below the lower lip. A biopsy of the lesion is sent to pathology. Squamous cell carcinoma (SCC) commonly appears on the face, especially around the lips. It more commonly occurs around the lower lip, whereas basal cell carcinoma is more frequently seen on and around the upper lip. Even with these clinical clues, biopsy is still required for a definitive diagnosis.
On biopsy of SCC, keratinization is often evident (as shown in this image). This type of cancer is locally invasive, but rarely metastatic. Sun exposure is?

Answer 15

the primary cause of SCC, but industrial carcinogens such as tars and oils, old burn scars, arsenic, and exposure to ionizing radiation are also risk factors. Grossly, SCC appears as a scaly, erythematous, ulcerated lesion with irregular borders, as seen in the image below.

Question 16

Acral lentiginous melanoma differs grossly and microscopically from SCC. Actinic keratoses are premalignant lesions that can lead to SCC. Basal cell carcinoma (BCC) often appear on face and lips, but have a predilection for the upper lip. Melanoma is a ?

Answer 16

melanocyte-derived neoplasm that is malignant.

Question 17

This patient, who presents with fever, malaise, pharyngitis, hepatosplenomegaly, and lymphadenopathy, is suffering from infectious mononucleosis, which is most commonly caused by Epstein-Barr virus (EBV). The lab findings further support this diagnosis. The peripheral smear shown in the image demonstrates large atypical lymphocytes with prominent nucleoli (abnormal circulating cytotoxic T lymphocytes). Mononucleosis is diagnosed by the monospot test, wherein heterophil antibodies are detected by agglutination of sheep or horse RBCs. The infection is transmitted by personal contact, typically through saliva, which is why it is sometimes called?

Answer 17

“the kissing disease.” EBV infection can be complicated by splenic rupture, and patients should be counseled to avoid contact sports until splenomegaly resolves.
EBV infection is associated with nasopharyngeal carcinoma, as well as CNS lymphoma and Hodgkin lymphoma

Question 18

Rheumatic heart disease is associated with recurrent untreated group A streptococcal infections (most commonly pharyngitis).
Cervical carcinoma is associated with certain subtypes of HPV.
MALT lymphoma is associated with ?

Answer 18

H. pylori infection, which presents with signs such as gastritis or ulcers (gastric or duodenal).
Acute glomerulonephritis can sometimes occur after group A streptococcal skin infections.

Question 19

This patient presents with lethargy and bone pain. Additionally, he has proteinuria indicated by the frothy urine, and his X-ray demonstrates several hypodense, lytic bone lesions. He also has an increase in γ-globulins on his serum protein electrophoresis that is commonly referred to as an M-spike. This clinical picture is strongly indicative of multiple myeloma.
One of the complications of multiple myeloma is ?

Answer 19

systemic primary amyloidosis, in which amyloid is deposited in mesangium and subendothelial space. This eventually results in glomerular obliteration and end-stage renal disease. Staining of amyloid with Congo red yields apple-green birefringence, as shown in the image.

Question 20

Rapidly progressive glomerulonephritis (RPGN) is unlikely because this patient does not have hematuria. Focal segmental glomerulosclerosis, minimal change disease, and diabetic glomerulosclerosis do cause?

Answer 20

proteinuria, yet these diseases do not account for this patient’s bone lesions or the protein spike on serum protein electrophoresis.

Question 21

This woman likely has a deep vein thrombosis (DVT) and has probably developed a pulmonary embolus (PE). Prolonged immobility (as during an airplane flight) is a risk factor, but patients who develop DVT/PE at a young age also often have an underlying hypercoagulable state. Factor V Leiden is the most common inherited cause of?

Answer 21

hypercoagulability. It occurs in 2%–15% of Caucasians and can predispose carriers to an increased risk of DVT, especially in the setting of venous stasis. The mutation results in an arginine-to-glutamine substitution at position 506 in factor V and makes the protein resistant to cleavage by protein C.

Question 22

he other options listed (prothrombin gene mutation, antithrombin III deficiency, Protein C, and Protein S deficiency) can also lead to?

Answer 22

venous thrombosis, but these are rare in the general population when compared to factor V Leiden.

Question 23

There is a notable inflammation of the hepatic portal (indicated by black arrows in the image) and the trabeculae are composed of multiple layers of malignant hepatocytes (yellow arrows point to gray Mallory bodies). The malignant hepatocyctes demonstrate hypercellularity, a high nuclear-to-cytoplasm ratio, and marked pleomorphism (variety of size and shape).
The location of the patient’s pain and his weight loss also are indicative of?

Answer 23

possible hepatic pathology. Hepatic bruit is found in some patients with HCC if the tumor is partially obstructing arterial flow in the liver. HCC is also associated with elevated alpha-fetoprotein levels.

The patient’s tatoo, which he obtained overseas, offers a possible etiologic clue, since nonsterile equipment can transmit infections. By now, you should be thinking Hepatitis C, which is transmitted by blood-to-blood contact and is a known risk factor for cirrhosis, which in turn predisposes the affected individual to HCC

Question 24

Cholangiocarcinoma is a malignancy in the biliary ducts that can be caused by chronic inflammation due to primary sclerosing cholangitis (PC) or parasites. In both cholangiocarcinoma and PSC, a condition in which inflammation causes stenosis of the bile ducts, a liver biopsy would appear normal. Hemangioma is a benign tumor and the biopsy would not show malignant changes. Hepatitis A is usually acquired via?

Answer 24

the oral-fecal route, does not cause a persistent disease state, and does not increase the risk of liver cancer. (Blood tests are often sufficient to make this diagnosis.)

Question 25

The newborn in the vignette has jaundice, hepatosplenomegaly, and difficulty breathing—all of which are common signs and symptoms of erythroblastosis fetalis. When the mother—who was likely Rh negative—first gave birth to an Rh-positive fetus, the fetal RBCs entered the mother’s circulation. The mother’s body then recognized the Rh antigen as foreign and produced antibodies against it. The initial anti-Rh antibodies made by the mother were IgM in nature and thus could not cross the placenta and harm the fetus. This resulted in?

Answer 25

her uncomplicated first pregnancy, during which the fetus did not develop erythroblastosis fetalis.

Question 26

Anti-Rh antibodies are found in Rh-negative women who have carried Rh-positive fetuses. If the woman becomes pregnant with a second Rh-positive fetus, the anti-Rh antibodies can lead to development of?

Answer 26

erythroblastosis fetalis of the newborn. RhoGAM is given to Rh-negative mothers to prevent erythroblastosis fetalis of the newborn.

Question 27

Mixing the mother’s serum with her own RBCs would provide no further information, because the mother is Rh negative and has not had any episodes of spontaneous hemolytic anemia.
If the mother’s child from her previous pregnancy were Rh negative, then the mother would not have formed anti-Rh antibodies.
If this pregnancy were with an Rh-negative child, there would be no erythroblastosis fetalis, because?

Answer 27

the mother herself is also Rh negative.
If the mother were already Rh positive, the fetus would also be Rh positive from maternal contribution, and no reaction would be seen.

Question 28

This is a question for which remembering the First Aid mnemonics will really help!
This patient has a history of kidney stones. Calcium stones are by far the most common type of stone. The most common cause of hypercalcemia is excess parathyroid hormone (PTH) release by the Parathyroid glands, caused by either enlargement of the glands or a tumor such as an adenoma.

She also has epigastric pain, diarrhea, and elevated gastrin levels. Causes of elevated gastrin levels include tumors of the pancreas or small intestine. The epigastric pain, elevated gastrin levels, and diarrhea are classic signs of?

Answer 28

Zollinger-Ellison syndrome, most likely caused by a Pancreatic gastrinoma.

So the patient has Parathyroid dysfunction and a Pancreatic tumor. That’s two “P’s.” What’s the third?

Pituitary tumors. This patient most likely has the hereditary condition multiple endocrine neoplasia type 1 (MEN1). MEN1 typically presents with benign tumors at multiple sites:

A parathyroid adenoma
A pancreatic endocrine tumor as found in Zollinger-Ellison syndrome, an insulinoma, or a VIPoma
A pituitary tumor
The most common tumor of the pituitary gland is a prolactinoma, which causes elevated serum prolactin levels. Patients with prolactinoma present with bilateral nipple discharge and enlarged breasts; when the tumor is large enough, they have other hormonal abnormalities.

Question 29

Elevated catecholamine levels are associated with pheochromocytoma found in MEN2A/MEN2B. Thyroid hormone levels are not affected in MEN1 but are elevated in Graves disease. Parathyroid adenomas in MEN1 and the resultant hypercalcemia cause?

Answer 29

decreased (not increased) serum phosphate levels.