Hem n Onc 8-5 (3)

Question 1

This patient is presenting with hypertension, a palpable purpuric rash, numbness, tingling, and a history of allergies. A blood test reveals perinuclear antinuclear cytoplasmic antibodies (p-ANCA). All of these clues indicate that this patient has Churg-Strauss syndrome.
Churg-Strauss is a rare granulomatous vasculitis affecting small vessels that is known to be associated with?

Answer 1

eosinophilia and p-ANCA.

Question 2

c-ANCA (not p-ANCA) is associated with granulomatosis with polyangiitis (previously known as Wegener granulomatosis). Coronary aneurysms are seen in Kawasaki disease, a vasculitis of childhood. Hepatitis B seropositivity is seen in polyarteritis nodosa, and Raynaud phenomenon is associated with?

Answer 2

Buerger disease, a small- and medium-vessel vasculitis.

Question 3

Suspect Churg-Strauss syndrome in a patient with a history of asthma, eczema, rash, and numbness and tingling in the extremities. It is associated with an?

Answer 3

eosinophilia and positive p-ANCA.

Question 4

This patient presents with left-sided ataxia and a hemangioblastoma in his right retina. Together, these findings are suggestive of von Hippel-Lindau (VHL) disease.
Patients with von Hippel-Lindau (VHL) disease, which is autosomal dominant, have hemangioblastomas, or cavernous hemangiomas of the retina, cerebellum, and medulla. In addition to a retinal hemangioblastoma, this patient likely has a cerebellar hemangioblastoma, suggested by his ataxia.

Patients with VHL disease are at increased risk of developing?

Answer 4

bilateral renal cell carcinoma ; 10% develop the so-called classic triad of flank pain, palpable flank mass, and hematuria. The deletion of the tumor-suppressing VHL gene on chromosome 3p causes VHL disease.

Question 5

This gene deletion does not affect the appearance of colon cancer. Colon cancer is more often a sequela of familial adenomatous polyposis (FAP), which is caused by the deletion of the APC gene on chromosome 5.

Astrocytomas are central nervous system tumors that arise in the cranial vault and may be associated with tuberous sclerosis. Tuberous sclerosis is an autosomal dominant genetic disorder caused by a mutation in either the TSC1 or TSC2 gene. The penetrance of tuberous sclerosis is not complete and symptoms can vary. Clinical features of tuberous sclerosis may include ash leaf spots, angiofibromas, and hamartomas (including glioneural hamartomas and subependymal nodules).

Retinal hemangioblastomas, however, are not associated with?

Answer 5

tuberous sclerosis. Although the patient’s fundoscopic image could be interpreted as showing a retinal hamartoma, other symptoms of tuberous sclerosis, such as facial lesions, hypopigmented spots on the skin, and seizures are not present.

Depression is a comorbidity of many diseases, but in a patient with VHL disease there is a higher risk of developing renal cell carcinoma.

Question 6

This patient presents with a painless neck mass and a trio of constitutional “B” symptoms: fever, night sweats, and weight loss. Although the most common cause of an enlarged cervical node in a young patient is infection, there are a several things that make infection an unlikely diagnosis in this patient:
The patient’s lymph node is painless (lymphadenopathy due to infection is typically tender).
Although the patient has a fever, which is consistent with infection, the patient’s other symptoms (massive weight loss and night sweats) are more consistent with “B” symptoms in?

Answer 6

lymphoma.
The biopsy specimen does not show morphologic evidence of an infectious process (such as follicular hyperplasia or interfollicular expansion).
The patient’s painless lymphadenopathy and “B” symptoms are suggestive of lymphoma. Hodgkin lymphoma has a bimodal distribution, with one peak in young patients and another peak in older patients; overall, the disease is more common in males. The biopsy specimen shown in the stem, which indicates a classic Reed-Sternberg cell amidst a background of lymphocytes, is diagnostic of lymphocyte-rich Hodgkin lymphoma.

Question 7

In some subtypes of Hodgkin lymphoma, including the lymphocyte depletion, mixed cellularity, and lymphocyte-rich subtypes, the Reed-Sternberg cells are infected with ?

Answer 7

Epstein-Barr virus (EBV). EBV is a herpesvirus; members of this family have a double-stranded, linear DNA genome. The exception is the nodular sclerosing subtype,which is 90% EBV negative.

Question 8

Viruses with a double-stranded, circular DNA genome include the papillomaviruses and the polyomaviruses. None of these viruses are associated with this patient’s condition.

Viruses with a single-stranded (–), linear RNA genome include the orthomyxoviruses, paramyxoviruses, rhabdoviruses, and filoviruses. None of these viruses are associated with this patient’s condition.

Viruses with a single-stranded (+), linear RNA genome include?

Answer 8

the picornaviruses, caliciviruses, flaviviruses, togaviruses, coronaviruses, and retroviruses. None of these viruses are associated with this patient’s condition.

Viruses with a single-stranded, circular RNA genome include the arenaviruses, bunyaviruses, and delta viruses. None of these viruses are associated with this patient’s condition.

Question 9

This patient’s tender swollen right calf in the setting of a previous history of calf pain and family history of hypercoagulability is suggestive of a new deep venous thrombosis (DVT). Given that the patient has no history of stasis (recent surgery, long drive or flight) or endothelial damage and considering that his brother had an infarction of the mesenteric vein at a young age, this patient most likely has an inherited thrombophilia. The most common inherited thrombophilia in white individuals is?

Answer 9

factor V Leiden mutation.

Question 10

Although other hereditary disorders of hypercoaguability, such as protein S deficiency, prothrombin gene mutation, and antiphospholipid antibody syndrome, could explain recurrent thrombotic events, they are not the most prevalent thrombophilias in white individuals and are therefore not the most likely cause of this patient’s thrombosis. Von Willebrand factor deficiency leads to?

Answer 10

Prolonged bleeding and thus does not cause recurrent thrombotic events.

Question 11

This patient presents with a hard, nontender, movable lump and a history of menopause at age 56. Late menopause (>55 years old) is a known risk factor for breast cancer. Because this patient went through menopause 2 years ago, at age 56, she has had an increased lifetime exposure to estrogen, which increases her risk for breast cancer. Other risk factors include ?

Answer 11

female gender, older age, early menarche (<12 years old), delayed first pregnancy (>30 years old), and family history of a first-degree relative with breast cancer at a young age.

Question 12

Caffeine intake, history of a nonbloody cyst, St. John’s Wort use, and multiparity do not increase lifetime exposure to estrogen and therefore do not increase?

Answer 12

the risk for breast cancer. A fibroadenoma only slightly increases the risk for breast cancer.

Question 13

This patient presents with the classic signs and symptoms (night sweats, fever, and weight loss) of Hodgkin lymphoma. The diagnosis is confirmed by the presence of a Reed-Sternberg cell, which are large cells with lobed nuclei that look like owl’s eyes, indicated by the circle in the image.
Vinblastine is part of the ABVD regimen (Adriamycin [doxorubicin], Bleomycin, Vinblastine, and Dacarbazine) used to treat Hodgkin lymphoma. It inhibits microtubular formation of the mitotic spindle, so that affected cells cannot pass through metaphase. Vinblastine is used to treat?

Answer 13

both Hodgkin and non-Hodgkin lymphomas, as well as many solid tumors. Adverse effects include alopecia, constipation, myelosuppression, and, rarely, neurotoxicity.

Question 14

The other drugs listed do not play a role in treating Hodgkin lymphoma. Cyclosporine is an immunosuppressant used to treat autoimmune disease. Isoniazid is an antibiotic that is part of the multidrug regimen for treating tuberculosis. All-trans retinoic acid is used to treat ?

Answer 14

the APL form of acute myelogenous leukemia. The monoclonal antibody imatinib is used to treat CML.

Question 15

Firm prostate nodules and unintentional weight loss suggest prostate cancer. The fact that the patient is having back and pelvic pain suggests that his cancer has progressed to metastatic disease. Metastases, from the prostate to the bone, disrupt the normal resorption process of bone formation, leading to a decreased serum calcium level. The prostate-specific antigen (PSA) level is typically elevated in?

Answer 15

prostate cancer. The alkaline phosphatase level should be increased as it is a marker of bone formation.

Question 16

PSA levels should always be expected to be high in the setting of prostate cancer. When prostate cancer metastasizes to bone it characteristically leads to “osteoblastic lesions,”i.e., new bone growth. Because of the new bone growth, alkaline phosphatase is elevated, not lowered, as would be expected with osteolytic lesions. Similarly, the serum calcium level would decrease?

Answer 16

in the setting of metastatic prostate cancer for two reasons: normal bone resorption is disrupted, and calcium is used in the formation of new bone.

The other sets of lab values are not associated with this patient’s condition. The other sets show markers for a healthy patient (A), for a patient with Paget disease of bone (B), for vitamin D deficiency (C), and for chronic renal failure (E).

Question 17

The woman presents with signs of fever, hypotension, tachypnea, leukocytosis, and urine nitrites. As a result, it is highly likely that this patient is presenting with sepsis. In sepsis (which may be secondary to bacterial, viral, fungal, or parasitic infection), systemic inflammation leads to cytokine activation and subsequent activation of the coagulation cascade. With this patient’s additional signs of petechiae, purpura, and intractable epistaxis, as well as the lab findings of prolonged INR and thrombocytopenia, she is most likely suffering from ?

Answer 17

Disseminated intravascular coagulation (DIC) secondary to gram-negative sepsis.
Although DIC is not a hallmark of sepsis, it is most commonly associated with sepsis. Other causes of DIC include malignancy, acute pancreatitis, trauma (particularly neuro-trauma), transfusion reactions, and obstetric complications.

The underlying mechanism of DIC is activation of the coagulation cascade, which leads to microthrombi and global consumption of platelets, fibrin, and coagulation factors.

Question 18

Toxin-producing bacterial infection from hemolytic-uremic syndrome (HUS) typically results in hemolytic anemia, acute kidney failure (uremia, elevated creatinine), and thrombocytopenia with PT/INR and PTT unaffected.
Absence of protease responsible for cleaving von Willebrand factor represents thrombotic thrombocytopenic purpura (TTP). Although schisocytes may be present on peripheral smear, lab findings include?

Answer 18

a decreased platelet count with normal prothrombin time and partial thromboplastin time.
Autoimmune hemolytic anemia results from autoantibodies directed at the RBC membrane. In autoimmune hemolytic anemias, one would not expect thrombocytopenia or schistocytes on the blood smear.
Antibodies directed at platelet membrane antigens are seen in immune thrombocytopenic purpura.

Question 19

Since BRCA1 is a tumor-suppressor gene, and this woman carries only one functional copy of the gene, there is a high probability that a spontaneous mutation will disrupt that functioning copy. This predisposes the patient to ovarian or breast carcinomas. This process is called ?

Answer 19

loss of heterozygosity and is necessary for heterozygous tumor-suppressor mutations to cause cancer.

Familial adenomatous polyposis (FAP) is a similar disease, in which the APC tumor-suppressor gene on chromosome 5 is deleted. Over time, there is a 100% chance that a second hit will occur, leading to a loss of heterozygosity that strongly predisposes colorectal cells to dysplasia, and eventually to malignant transformation. This is known as the “two-hit” hypothesis: a person will develop cancer if he or she inherits one mutated gene and incurs a second mutation after conception, or if he or she incurs two mutations or “hits” after conception.

Question 20

The other answer options are incorrect because Burkitt lymphoma, chronic myelogenous leukemia, follicular lymphoma, and multiple endocrine neoplasia types 2A and 2B are caused by?

Answer 20

dominant gain-of-function mutations. Thus, they are not inherited in the same pattern as in our patient.

Question 21

The patient’s long smoking history, symptoms of night sweats, fever, and weight loss indicate a malignancy. The presence of Reed-Sternberg cells in the image indicate Hodgkin lymphoma, which describes a group of lymphoid neoplasms that generally arise in a single node or a contiguous group of nodes, before spreading to anatomically adjoining nodes. There are four main types of classical Hodgkin lymphoma:?

Answer 21

(1) nodular sclerosing (2) mixed cellularity (3) lymphocyte rich, and (4) lymphocyte depleted.
There is one additional type called nodular lymphocyte-predominant Hodgkin lymphoma. Hodgkin lymphoma constitutes only 0.7% of neoplasms in the United States. Hodgkin lymphoma has a bimodal incidence curve, diagnosed in young adults (age 15–35 years) or in older adults (age >55 years).

Although the cause of Hodgkin lymphoma is unknown, genetic susceptibility and environmental associations play a role. There is increasing evidence that the Epstein-Barr virus (EBV) may be involved in the pathogenesis of Hodgkin lymphoma in some cases. EBV is a double-stranded herpesvirus that causes infectious mononucleosis, and patients with a history of this infection are at an approximately three-fold increased risk for Hodgkin lymphoma.

Question 22

Bartonella henselae causes cat-scratch disease, which is a granulomatous reaction to a bacterium. This disease does not show Reed-Sternberg cells but, as described, a granulomatous reaction.
Sarcoidosis shows a noncaseating granulomatous reaction.
Human T-cell lymphotropic virus, type 1 (HTLV-1) is not associated with lymphomas, but rather is associated with?

Answer 22

skin lesions and hepatosplenomegaly.
Though this patient has strong risk factors for developing lung cancer—the number-one cause of cancer death in the United States—the biopsy histology points to Hodgkin lymphoma as a diagnosis.

Question 23

This neonate, who has an older sibling, was born 6 hours ago. Based on information provided by the mother, she turned down medical interventions during her pregnancy, which may have included prophylactic Rho immune globulin (RhoGAM) injections. We can infer that not only is the mother Rh-negative, but she has previously been exposed to Rh-positive fetal blood with the birth of her first child. This information, along with the CBC showing anemia and the physical exam findings of swollen face and enlarged liver, support a diagnosis of?

Answer 23

erythroblastosis fetalis, or hemolytic disease of the newborn.

Question 24

An infant with biliary atresia, biliary cirrhosis, or hepatic atresia would present with jaundice but would not have anemia due to hemolysis. Nonpathologic neonatal jaundice is caused by normal neonatal changes in bilirubin metabolism, resulting in?

Answer 24

increased bilirubin production, decreased bilirubin clearance, and increased enterohepatic circulation. It usually manifests after the first day of life.

Question 25

Recent-onset intractable back pain and unexplained weight loss in an elderly patient must make you suspect cancer. The bone scan suggests lesions on the axial skeleton (accounting for his back pain), and bone metastases are much more common than primary bone tumors.
So next, look at the tissue biopsy (from the prostate), which shows a single layer of cuboidal epithelium with enlarged nuclei and visible nucleoli and an absence of the outer basal layer normally seen in normal glands. This architecture is classic for?

Answer 25

adenocarcinoma, and your conclusion is supported by the fact that prostate adenocarcinoma frequently metastasizes to bone.

The cancers that most commonly metastasize to bone can be remembered with the mnemonic BLT with a Kosher Pickle, with B standing for Breast, L for Lung, T for Thyroid, K for Kidney and P for Prostate.

Question 26

The other answer choices are characterized by features that are not found in this histologic image. Papillomas are benign, finger-like processes that arise from surface epithelium. Sarcoma of the bone is characterized by malignant cells producing osteoid or bone with calcifications. A teratoma is a neoplasm derived from?

Answer 26

all three germ cell layers and demonstrates proliferation of multiple tissue types. Transitional cell carcinoma involves proliferation of multiple layers of epithelium.

Question 27

This patient’s presenting symptoms of weight loss, night sweats, and painless lymphadenopathy are indicative of Hodgkin lymphoma. This diagnosis is confirmed by the presence of Reed-Sternberg cells(frequently referred to as “owl’s eye” cells) on a biopsy specimen. The next step after diagnosis is staging of lymphoma to determine potential treatment and prognosis. Staging is completed by means of a thorough history, physical examination, and positron emission tomography/computed tomography imaging of the chest, pelvis, and abdomen. The involvement of multiple lymph node regions and extranodal involvement indicate?

Answer 27

a higher Ann Arbor stage for Hodgkin lymphoma, and therefore, a poorer prognosis.