Hem n Onc 8-5 (2)

Question 1

This patient is 69 years old and presents with diplopia, weakness in his lower extremities that improves with exertion, and diminished deep tendon reflexes. He has a history of smoking, and a cancer work-up reveals metastasis throughout the patient’s body.
His X-ray shows a central lung cancer, which is likely the primary malignancy. His proximal muscle weakness, decreased deep tendon reflexes, and diplopia point toward a?

Answer 1

Paraneoplastic syndrome.

Question 2

Small cell lung carcinoma is a neoplasm of neuroendocrine Kulchitsky cells that frequently produces paraneoplastic syndromes, including ectopic production of ACTH, ADH, and Lambert-Eaton syndrome.

Lambert-Eaton syndrome involves the production of?

Answer 2

Antibodies against presynaptic calcium channels at the neuromuscular junction. This produces proximal muscle weakness, decreased deep tendon reflexes, and rarely, diplopia. Ocular and cranial nerve involvement can also occur in Lambert-Eaton, but are much more common in myasthenia gravis. Myasthenia gravis (MG) involves the production of autoantibodies to acetylcholine receptors at the neuromuscular junction. Symptoms often include muscle weakness and diplopia, though, with MG, weakness can worsen with use. MG is not associated with small cell lung carcinoma; however, it is occasionally seen with thymoma.

Question 3

Autoimmune disease with anti-double-stranded DNA, anti-DNA, and anti-Smith antibodies describes systemic lupus erythematosus. The condition is associated with multiple symptoms, including skin rash, hair loss, fever, and anorexia. It is usually seen in females 14–45 years old.

Symmetric morning stiffness, joint inflammation, fever, and fatigue are symptoms of?

Answer 3

rheumatoid arthritis, which is an inflammatory disorder of synovial joints with pannus formation. This condition is seen mostly in females.

Reactivation of a peripheral subpleural parenchymal lesion and hilar lymph nodes, describes secondary tuberculosis, which is uncommon except in immunocompromised patients.

Question 4

Ocular and cranial nerve involvement can also occur in Lambert-Eaton, but are much more common in myasthenia gravis. Myasthenia gravis (MG) involves the production of autoantibodies to acetylcholine receptors at the neuromuscular junction. Symptoms often include?

Answer 4

muscle weakness and diplopia, though, with MG, weakness can worsen with use. MG is not associated with small cell lung carcinoma; however, it is occasionally seen with thymoma.

Question 5

The patient is presenting with mucosal bleeding, epistaxis, and symptoms of anemia. Laboratory values also reveal increased bleeding time and increased partial thromboplastin time. This, along with the finding that his mother has a history of anemia, makes it likely that the patient has?

Answer 5

von Willebrand disease (vWD), the most common inherited bleeding disorder. This disorder is a result of functional problems with von Willebrand factor (vWF). vonWillebrand factor serves as the ligand for platelet adhesion to a damaged vessel wall. It is also the plasma carrier for factor VIII.

Question 6

Bernard-Soulier syndrome is an inherited defect in platelet adhesion caused by decreased surface expression of glycoprotein Ib. Bleeding time would be increased, but partial thromboplastin time would be normal.
Glanzmann disease is a disorder in which platelets do not have the glycoprotein IIb/IIIa receptor, which normally binds fibrinogen. Bleeding time would be increased, but partial thromboplastin time would be normal.
Hemophilia A is an X-linked recessive disorder that causes?

Answer 6

factor VIII deficiency. Bleeding frequently occurs in joints and the retroperitoneal space. Laboratory tests would typically reveal a normal prothrombin time and normal bleeding time (since there is no inherent platelet disorder).

Vitamin K deficiency impairs coagulation factors II, VII, IX, and X, which depends on vitamin K–mediated γ-carboxylation. Patients with vitamin K deficiency tend to have an elevated prothrombin time.

Question 7

The patient is presenting with signs and symptoms of anemia (eg, fatigue, pale conjunctivae, decreased hemoglobin and hematocrit), thrombocytopenia (eg, petechiae and decreased platelets), and leukocytosis with a predominance of lymphocytes. The X-ray depicts a large mediastinal mass, and a biopsy reveals cells with light blue, scanty, and nongranular cytoplasm, which represents myoblasts. This clinical picture is strongly suggestive of ?

Answer 7

lymphoblastic lymphoma.

Question 8

Chronic lymphocytic leukemia, unlike lymphoblastic lymphoma, typically manifests in older individuals with the insidious onset of lymphadenopathy, splenomegaly, and smudge cells on peripheral smear.

Follicular lymphoma is a non-Hodgkin lymphoma that occurs in middle-aged patients with painless, generalized lymphadenopathy.

Although patients with Hodgkin disease typically present with mediastinal lymphadenopathy, profound bone marrow suppression with the presence of blasts favors a diagnosis of ?

Answer 8

lymphoblastic lymphoma over Hodgkin disease.
B-cell acute lymphoblastic lymphoma (ALL) predominantly occurs in children, and commonly spreads to the CNS and testes in males.

Question 9

This asymptomatic patient presents for a routine physical exam and has a mildly decreased hemoglobin. Because the MCV is decreased, it is considered a microcytic anemia. The two most common causes of microcytic anemia are?

Answer 9

iron deficiency anemia and thalassemia. Definitive diagnosis of either disease requires iron studies and a hemoglobin electrophoresis. However, a presumptive diagnosis can be made by reviewing the remaining CBC indices.

Question 10

This patient’s Tunisian ethnicity is also consistent with ß-thalassemia, which is more common in individuals from countries around the Mediterranean, North Africa, the Indian subcontinent, and Eastern Europe.

A common morphologic finding in thalassemia is ?

Answer 10

target cells (red cells with a condensation of hemoglobin in the center, giving them a target appearance). Several target cells can be seen in the image above.

Question 11

Helmet-shaped red cells are seen in disseminated intravascular coagulation (DIC). The blood in DIC shows a microangiopathic hemolytic anemia, characterized by schistocytes (fragmented red cells, such as helmet cells).
Neutrophils with an increased number of nuclear lobes (or hypersegmented neutrophils) are indicative of megaloblastic anemia, a macrocytic anemia due to decreased B12 and/or folate.
Crescent-shaped red cells are seen in?

Answer 11

sickle cell anemia, a genetic disorder in which a point mutation in the beta globin chain causes hemoglobin polymerization (and sickle cell formation) at low oxygen tension. Sickle cell anemia is typically normocytic (the MCV is usually within the normal range), and the RBC is normal to decreased. The RDW is increased during sickle cell crises due to the variation in cell size.
RBCs lacking central pallor (spherocytes) are seen in hemolytic anemias and in hereditary spherocytosis, which are normocytic anemias.

Question 12

This 69-year-old woman presents to her physician with increasing fatigue, weakness, and anorexia. The blood smear shows a microcytic, hypochromic anemia with numerous RBCs that have central pallor. In a female patient at this age, the most likely cause of ?

Answer 12

a microcytic, hypochromic anemia is iron deficiency. Common causes of iron deficiency are chronic bleeding, malnutrition/malabsorption disorders, or increased demand (eg, in pregnancy). Older patients with a colorectal malignancy will often present with signs and symptoms of iron deficiency anemia because of occult blood loss in the stool.

Question 13

Cold agglutinin disease is an autoimmune hemolytic anemia often associated with a previous infection with Mycoplasma pneumoniae or the Epstein-Barr virus. The blood smear often shows clumps of RBCs.
Lead poisoning also causes a microcytic, hypochromic anemia, but a blood smear would show basophilic stippling, due to the fact that lead also inhibits RNA degradation.
Mutations in the β-globin chain are characteristic of?

Answer 13

sickle cell anemia and β-thalassemia. These diseases tend to manifest early in life with target cells on the peripheral blood smear.
A nutritional deficiency of folic acid produces megaloblastic anemia, with characteristic hypersegmented neutrophils and macrocytic RBCs.

Question 14

This patient presents with flank tenderness, a palpable abdominal mass and a 50 pack-year smoking history. The CT scan show a mass in the kidney. Flank tenderness, a palpable mass in the abdominal area, and hematuria are the classic triad of symptoms for?

Answer 14

renal cell carcinoma. This carcinoma is most common in men aged 50–70 years.

Question 15

Angiomyolipoma is a benign tumor composed of fat, smooth muscle cells, and blood vessels, and is often asymptomatic. Autosomal dominant polycystic kidney disease is a disorder leading to bilaterally enlarged kidneys, hypertension, hematuria, and renal failure. Neuroblastoma is one of the most common pediatric cancers caused by?

Answer 15

a tumor of the adrenal medulla. Wilms tumor, another pediatric tumor, is an asymptomatic unilateral abdominal mass.

Question 16

This patient presents with night sweats, weight loss, and supraclavicular and mediastinal lymphadenopathy. These symptoms are all classic signs of Hodgkin lymphoma. Mediastinal lymphadenopathy is a classic finding of ?

Answer 16

Hodgkin lymphoma, particularly the nodular-sclerosing subtype

Question 17

Nodular-sclerosing Hodgkin lymphoma usually presents in young women. It is characterized by lacunar cells, a variant of malignant Reed-Sternberg (RS) cells; cytoplasmic retraction occurs during tissue fixation, causing them to appear?

Answer 17

separated from other cells by a clear space.

Question 18

Burkitt lymphoma occurs more commonly in children.
Follicular lymphoma involves a t(14;18) translocation, which leads to overactivation of BCL-2.
Diffuse large B-cell lymphoma is the most common lymphoma occurring in adults, but in some cases, it does affect children.
T-cell lymphoblastic lymphoma typically occurs in ?

Answer 18

children, and associated mediastinal masses are common.

Question 19

This patient presents with galactorrhea, recurrent abdominal pain, a history of kidney stones and depression. She has a family history of a brother with a pancreas tumor of an unknown type. In this patient, the galactorrhea is highly suggestive of a pituitary prolactinoma. Her duodenal ulcer—signaled by her abdominal pain that is relieved by eating— may be seen in the setting of ?

Answer 19

Zollinger-Ellison syndrome, caused by a gastrinoma.

gastrin-secreting tumor of the pancreas or duodenum).

The patient’s diagnosis is most likely multiple endocrine neoplasia type I (MEN 1). This syndrome, caused by a mutation in the MEN1 gene, is associated with tumors or hyperplasia of the pancreas, pituitary, and parathyroid. The most common manifestation of the syndrome is hyperparathyroidism, which causes hypercalcemia and hypophosphatemia.

Question 20

Although glucagonoma of the pancreas can lead to hyperglycemia, the patient does not exhibit any of the classic signs of hyperglycemia. Hyperphosphatemia is a condition marked by abnormally high levels of serum phosphate. Hyperuricemia is indicative of?

Answer 20

underlying renal insufficiency, diuretic use, or alcohol consumption. The syndrome of inappropriate ADH secretion (SIADH), a paraneoplastic syndrome from underlying small cell lung cancer, can cause hyponatremia.

Question 21

This patient presents with symptoms of unintentional weight loss, increased perspiration, and increased appetite. The micrograph of the specimen obtained from the pelvic mass shows a tumor with a number of mature thyroid follicles. Thus she most likely has?

Answer 21

struma ovarii, a monodermal teratoma that contains thyroid tissue. Like this patient, between 5% and 15% of patients with struma ovarii present with symptoms of overt hyperthyroidism, including unintentional weight loss, increased perspiration, and increased appetite. These patients are at risk for a malignant thyroid carcinoma arising from the tumor.

Question 22

Krukenberg tumors are ovarian metastases from primary gastrointestinal tumors, which would appear the same as the primary tumor under a microscope. Immature teratomas are a rare form of ovarian cancer more commonly seen in younger women, and they contain both mature and embryonal tissue. An ovarian choriocarcinoma would include?

Answer 22

Proliferating trophoblast tissue, which would be seen in a biopsy specimen. Thecoma-fibromas are composed of lipid-containing cells. None of these tumors would demonstrate thyroid follicles on pathologic examination.

Question 23

This young patient presents with lymphadenopathy. If no other historical or physical examination findings were present, the first thing to think about would be infection. However, his clinical signs are described as “B” symptoms and point to something more serious (2 months of profuse sweating, fevers, and significant weight loss). Also, the fact that there are affected nodes in two different body regions is concerning. At this point, our top two diagnoses are related to?

Answer 23

malignancy: lymphoma and leukemia. His CBC is normal, which makes leukemia unlikely, because leukemias typically present with a high white blood cell count and depressed red blood cell and platelet counts.

Question 24

Acute lymphoblastic leukemia (ALL) is unlikely in this case, given the normal blood counts and the lymph node biopsy specimen that does not reveal lymphoblasts.
Chronic lymphocytic leukemia is very unlikely to occur in a 20-year-old patient; it typically occurs in older patients.
Burkitt lymphoma is not high on the differential diagnosis list for this patient. It does occur in younger patients, but it typically presents with a fast-growing mass in the mandible or abdomen.
Hairy cell leukemia typically presents in men in their fifties and sixties. Clinical signs and symptoms include?

Answer 24

massive splenomegaly (which this patient does not have), but lymph nodes are not typically affected. The CBC, which shows normal blood counts, argues against hairy cell leukemia, which is typically associated with one or more cytopenias.

Question 25

“B” symptoms (fever, night sweats, fatigue, weight loss) and the bump around lymph nodes is concerning for malignancy. This patient’s biopsy histology shows a binucleated cell with prominent nucleoli in the center of the image, surrounded by lymphocytes. This is a classic picture of a Reed-Sternberg (RS) cell, indicating the patient has?

Answer 25

Hodgkin lymphoma. Hodgkin lymphoma is a lymphoproliferative neoplasm that typically affects young adults, especially men, and presents with fever, night sweats, and weight loss. The presence of RS cells is essential in the diagnosis of any of the Hodgkin lymphoma variants. Vincristine, a microtubule inhibitor, is especially effective in the treatment of Hodgkin lymphoma. Other drugs that could be used include vinblastine, bleomycin, and doxorubicin.

Question 26

Imatinib is a tyrosine kinase inhibitor used in chronic myeloid leukemia (CML) as well as other tumors.
Raloxifene is an estrogen receptor antagonist used in estrogen-receptor positive breast cancer.
Trastuzumab is an antibody that blocks the HER-2 receptor, which is present in some cases of breast cancer.
Valacyclovir is an antiviral agent used in?

Answer 26

the treatment of herpes infection.

Question 27

A previously healthy male presents with increasing fatigue, weakness, shortness of breath, headache and lightheadedness, all symptoms that suggest the possibility of anemia. He has a family history of relatives having similar symptoms, which points in the direction of a hereditary disorder.
The CBC shows a normocytic anemia with normal WBC and platelet counts. Without even looking at the blood smear, this rules out microcytic anemias (such as iron-deficiency anemia and thalassemia) and macrocytic anemias (such as megaloblastic anemia).

This leaves the rather large category of ?

Answer 27

normocytic anemias, many of which are hemolytic anemias. The blood smear in this case is helpful, as it shows numerous spherocytes. These are smaller than normal RBCs that show no central pallor (see arrows in image). Spherocytes have an increased mean cell hemoglobin concentration (MCHC), which makes this answer choice correct.

Question 28

A β-globin chain mutation (which can happen in either ß-thalassemia or sickle cell anemia) is unlikely in this patient. β-thalassemia is a microcytic anemia, unlike the patient in the vignette, who has a normal MCV. It typically shows target cells on the blood smear. Sickle cell anemia is normocytic, but the blood smear shows sickle cells, and patients usually present with painful infarctions, neither of which are present in this patient.

Vitamin B12 deficiency causes megaloblastic anemia, which is a macrocytic anemia with hypersegmented neutrophils. This patient has a normocytic anemia, and the neutrophils in his blood smear are normally segmented.

A decreased ferritin level is diagnostic of iron-deficiency anemia, which is a?

Answer 28

microcytic anemia (vs the normocytic anemia in this patient). The blood smear in iron-deficiency anemia shows hypochromic, microcytic RBCs.

Heinz bodies are present in G6PD deficiency, a hereditary condition that manifests as an anemia with Heinz bodies (little balls of denatured globin chains) on supravital staining, and bite cells on regular Wright-Giemsa stain. This patient seems to have a familial component to his anemia. However, his blood smear does not show bite cells, which rules .out the possibility of G6PD deficiency.

Question 29

This girl recently emigrated from Africa, presents with a mass on her mandible, and has a recent history of fevers, night sweats, and fatigue. These symptoms and the patient’s country of origin raise the suspicion for ?

Answer 29

Burkitt lymphoma. Endemic African Burkitt lymphoma frequently manifests as masses involving the mandible and orbit (and less often the kidneys, ovaries, and adrenals)

Question 30

Endemic African Burkitt lymphoma is associated with the Epstein-Barr virus(EBV). EBV is also associated with heterophile-positive mononucleosis, oral hairy leukoplakia in patients infected with HIV, lymphoproliferative disorders in?

Answer 30

immunocompromised hosts (including Hodgkin and non-Hodgkin lymphomas), and nasopharyngeal carcinoma.

Two other types of Burkitt lymphoma, sporadic Burkitt and HIV-associated Burkitt, are associated with EBV in 15%–25% of cases. Infection with EBV types 16 and 18 poses the most risk for poor prognosis.

Although the other answer choices can be associated with a viral infection, none of them are associated with EBV. Cervical cancer is usually due to human papillomavirus, adult T-cell lymphomais caused by HTLV-1, Kaposi sarcoma is caused by HHV-8, and hepatocellular carcinoma is associated with hepatitis B and C viruses.

Question 31

Affected lymph nodes show a classic “starry sky” pattern of diffuse sheets of lymphoblasts with interspaced clear zones containing macrophages, as seen in the vignette image. The neoplastic cells typically show a?

Answer 31

translocation of the c-myc gene on chromosome 8 onto the immunoglobulin heavy-chain gene on chromosome 14.