Hem n Onc 8-5 (4)

Question 1

This child presents with a new viral upper respiratory infection (URI) and has a history of recurrent infections, conotruncal abnormality repair, and cleft lip/palate repair (surgical scar in image). He also has signs of hypocalcemia given the positive Chvostek sign on physical exam. Taken together, these findings suggest a diagnosis of DiGeorge syndrome.
DiGeorge syndrome is caused by a 22q11 chromosomal microdeletion that results in abnormal embryologic development of the 3rd and 4th branchial pouches. Use the mnemonic “CATCH-22” to remember the features of DiGeorge syndrome: Cleft palate, Abnormal facies, Thymic aplasia, Cardiac defects, and Hypocalcemia.

Because the thymus is normally derived from ?

Answer 1

the 3rd branchial pouch, children with DiGeorge syndrome can have a T-lymphocyte deficiency that predisposes them to recurrent viral and fungal infections (as seen in this patient).

Question 2

The first pharyngeal arch has several derivatives, which can be remembered by thinking of the letter “M”:
Maxillary processes (Maxilla, zygoMatic bone)
Mandibular processes (Meckel cartilage, Mandible, Malleus and incus, sphenoMandibular ligament)
Muscles of Mastication (teMporalis, Masseter, lateral and Medial pterygoid)
Mylohyoid
Derivatives of the first branchial arch are innervated by ?

Answer 2

the V2 and V3 branches of cranial nerve V. When the neural crest cells of the first pharyngeal arch fail to migrate, patients may develop Treacher Collins syndrome. Although Treacher Collins syndrome can manifest with facial abnormalities (most commonly mandibular hypoplasia), the findings in this patient are not consistent with this syndrome.

Question 3

The second branchial arch derivatives can be remembered by thinking of the letter “S”:
Stapes, Styloid process, Stylohyoid ligament
Muscles of facial expression (“Smile”)
Stapedius
Stylohyoid
PlatySma
The derivatives of the second arch are innervated by ?

Answer 3

Cranial nerve VII. The facial muscle twitching elicited in this patient by tapping the cheek (over the facial nerve) is called Chvostek sign and is associated with hypocalcemia. The second branchial arch is not involved in this patient’s condition.

Question 4

The second, third, and fourth branchial clefts form temporary cervical sinuses that are obliterated before fetal maturation. Normally they have no derivatives in the adult, but a persistent cervical sinus can result in a branchial cleft cyst within the lateral neck. The third branchial cleft has no association with this patient’s underlying condition.

The fourth branchial pouch gives rise to the dorsal wings, which develop into the superior parathyroid glands. Failure of parathyroid development results in ?

Answer 4

hypocalcemia, which is evidenced in this patient by a positive Chvostek sign on physical exam (tapping the cheek causes contraction of the facial muscles). Although the fourth branchial pouch is involved in this patient’s underlying condition, this embryologic structure does not give rise to any immunologic cells or organs.

Question 5

After an upper respiratory tract infection, this patient is experiencing persistent epistaxis, ecchymoses (including petechial hemorrhages seen in the image), and marked thrombocytopenia. However, his leukocyte count with differential, hematocrit, international normalized ratio (INR), and fibrinogen levels are within normal ranges. Therefore this patient’s history and laboratory test results suggest an isolated acquired thrombocytopenia caused by sequestration, destruction, and/or increased platelet consumption. Most likely the patient’s significant thrombocytopenia is a result of platelet destruction from?

Answer 5

idiopathic thrombocytopenic purpura (ITP), which is also known as immune thrombocytopenic purpura, an autoimmune disease most often triggered by a viral illness.

Question 6

Idiopathic thrombocytopenic purpura (ITP) is immune mediated destruction of platelets, commonly occurring in ?

Answer 6

children weeks after an upper respiratory infection. It manifests as ecchymosis, petechiae, mucosal bleeding, and marked thrombocytopenia.

Question 7

The finding of decreased megakaryocytes on bone marrow biopsy suggests a defect in platelet production, which may be the result of bone marrow malignancy, fibrosis, or aplastic anemia. Conditions such as these would produce abnormalities in the complete blood count (CBC).
Increased fibrin split products are a sign of activation of the coagulation cascade and are associated with thrombocytopenia when disseminated intravascular coagulation (DIC) occurs.
Conditions such as HUS, TTP, or DIC can cause?

Answer 7

schistocytes on peripheral blood smears when RBCs pass through fibrin strands and become sheared. These disorders have abnormalities in fibrinogen levels as well as the INR for DIC.
Vitamin K deficiency leads to decreased levels of clotting factors II, VII, IX, and X. This would result in a prolonged INR (prothrombin time).

Question 8

This patient presents with recurrent diarrhea, flushing, and respiratory wheezes. Her CT scan shows a 6-cm mass near the ileocecal junction. The symptoms and the CT finding suggest a diagnosis of carcinoid syndrome, a rare disorder caused by excessive serotonin secretion by metastatic small bowel and appendiceal tumors.
Carcinoid syndrome is characterized by diarrhea, cutaneous flushing, asthmatic wheezing, and right-sided valvular disease. Symptoms generally do not occur until metastasis to or beyond the?

Answer 8

liver occurs (red circle indicates the ileocecal mass), as serotonin undergoes extensive first-pass metabolism in the liver. When a patient presents with nonbloody diarrhea and abdominal tenderness, a CT scan is ordered to see if a neoplasm may be the cause of such symptoms.

Question 9

The other findings are not associated with this patient’s condition. Metastases of the ileocecal tumor to the lungs could potentially cause wheezing, but would not explain diarrhea and flushing. A VIP-secreting pancreatic mass (VIPoma) would lead to ?

Answer 9

diarrhea, dehydration, and hypokalemia, but would not explain the patient’s ileocecal mass, wheezing, or flushing.

Question 10

Bowel obstruction would likely be apparent on CT scan of the abdomen; however, this patient is not experiencing symptoms consistent with obstruction. Metastasis to the brain (intracranial mass) would likely produce?

Answer 10

neurologic deficits, none of which are present in this patient.

Question 11

A clinician reads a study on the diagnosis of iron deficiency anemia based on the presence of target cells in peripheral blood smears. The study was performed in a homogenous community in northern Europe. However, the clinician’s patient population is largely composed of people of African and Asian descent, populations that have an increased rate of hemoglobinopathies compared with northern Europeans. She is concerned that the predictive value of the test would be different if the study were reproduced using her patient population.

Which measure of quality does the study lack?

Answer 11

External validity

Question 12

In this case the clinician is concerned about the lack of external validity, which is the extent to which study results are applicable to a population other than the study population. External validity may be decreased if the study population varies from other populations by characteristics that might lead to?

Answer 12

significantly different results. Randomization is one way to help ensure appropriate external validity.

Question 13

External validity is a measure of accuracy, and lack of external validity leads to low accuracy. However, accuracy is not the correct answer to this question, because we don’t have enough data in the stem to evaluate its accuracy. Internal validity is a measure of ?

Answer 13

how well the study rules out alternative causes that could explain the results.

Confounding variables are always a concern for researchers; but given that the original study was performed in a homogenous population, the risk of confounding variables isn’t the clinician’s primary concern.

Question 14

Reliability assesses the consistency and reproducibility of a study were it to be repeated in a similar population, but again, this clinician is worried how the study’s findings would apply?

Answer 14

to her patient population and not whether they could be reproduced in the population similar to that in the original study.

Question 15

This 30-year-old woman presents with severe knee pain and a tender effusion on the knee. Based on the patient’s age and gender, as well as the location of the tumor, she most likely has a giant cell tumor. The appearance of the tumor—with a nonsclerotic and sharply defined border—is also a clue that this is a giant cell tumor.

Giant cell tumors are primary bone tumors that most commonly occur at ?

Answer 15

the epiphyseal end of long bones. They are benign, but locally aggressive tumors occurring most frequently at the distal femur or proximal tibia. Giant cell tumors have a peak incidence in people from age 20 to 40 years old. They tend to occur more often in women.

Question 16

Chondrosarcoma more commonly affects the axial skeleton. Ewing sarcoma classically shows onion-skinning on x-ray, and primarily affects younger boys. Osteochondromas affect the metaphysis of long bones. Osteosarcoma is more common in?

Answer 16

younger males and shows periosteal shadowing (Codman triangle) on x-ray.

Question 17

A 45-year-old man who has been HIV positive for the past 5 years presents with nonpitting edema of the feet and ankles and the lesions shown in the image. Since losing his job a few years ago, the patient has been intermittently homeless and has not seen his physician on a regular basis. On evaluation today, patient’s CD4 count is 300 cells/mm3.Which of the following is the most appropriate treatment for this patient’s lesions?

Answer 17

Interferon α2b
This patient’s lesions are consistent with Kaposi sarcoma, a cutaneous malignancy derived from lymphatic and vascular endothelial cells. Kaposi sarcoma is caused by human herpes virus-8 (HHV-8) and is most frequently seen in patients with AIDS. It can present with the skin lesions seen in the image (red to purple macules or plaques), with lymphedema of the extremities, genitalia, or face, or with spread to the oral mucosa, gastrointestinal tract, or respiratory tract.
Interferons are cytotoxic proteins that interfere with viral protein expression and DNA synthesis. α-Interferon (known by its pharmaceutical name Interferon α2b) is used for its leukocytic effects in patients with hepatitis B, hepatitis C, Kaposi sarcoma, leukemias, and malignant melanoma.

Question 18

Ganciclovir is a guanosine analog that is used to treat CMV infections in immunocompromised patients, but there were no indications that this patient had a CMV infection. IFNγ1b is used to treat patients with chronic granulomatous disease, but this patient has no evidence of this disease. Tacrolimus is an immunosuppressant used in organ transplant recipients, but this patient had not evidence of a recent organ transplant. Fosamprenavir is an inhibitor of?

Answer 18

HIV-1 protease, but is usually included in highly active antiretroviral therapy, and would not be appropriate to treat this patient’s lesions.

Question 19

This 5-month-old boy is meeting developmental milestones and has a normal exam except for an absent red reflex, as shown in the image in the vignette. An absent red reflex signifies an opacity blocking visualization of the retina. One possible cause of an absent red reflex is retinoblastoma.
Hereditary retinoblastoma is the most common primary intraocular malignancy of childhood and accounts for 10%–15% of cancers that occur within the first year of life. It frequently manifests with a “white reflex,” which can be accompanied by strabismus and pseudouveitis.

Hereditary retinoblastoma is caused by?

Answer 19

mutation of the RB1 gene, which codes for the retinoblastoma (Rb) protein. Rb protein is responsible for restricting the cell’s ability to progress from the G1 phase to the S phase of the cell cycle. Loss of functional Rb therefore causes cell cycle dysregulation.

Patients with hereditary retinoblastoma are at increased risk for soft tissue sarcomas, osteosarcomas, melanomas, and several types of brain cancer. The RB1 gene mutation is responsible for this increased risk of osteosarcoma. Osteosarcoma is the most common malignant primary bone tumor in childhood. It most frequently originates in the distal femur, proximal tibia, or proximal humerus. Other risk factors for osteosarcoma include Paget disease of the bone, bone infarcts, and radiation.

The RB1 mutation is not associated with the other answer choices.

Question 20

Esophageal adenocarcinoma is associated with Barrett esophagus. Other risk factors include Alcohol/Achalasia, Cigarettes, Diverticuli, Esophageal web (Plummer-Vinson)/ Esophagitis, and Familial and Gastroesophageal reflux disease. Risk factors for esophageal adenocarcinoma can be remembered with the mnemonic ABCDEFG.

Medullary carcinoma of the thyroid forms from parafollicular C cells and is associated with the MEN2A and 2B syndromes. Renal cell carcinoma is associated with von Hippel-Lindau syndrome. Squamous cell carcinoma is associated with?

Answer 20

a history of smoking. Urothelial carcinoma is also associated with tobacco, as well as with exposure to aniline dyes and cyclophosphamide.

Question 21

This patient presents with hypercalcemia, renal insufficiency and lytic bone lesions on x-ray after a recent fracture. These symptoms are consistent with multiple myeloma. Multiple myeloma (MM) is caused by an abnormal proliferation of plasma cells, which are mature antibody-secreting B lymphocytes.
This plasma cell neoplasm has a peak incidence between 50 and 60 years of age, and is characterized by ?

Answer 21

a hyperproliferation of plasma cells on bone marrow biopsy (indicated with arrows in the image). Patients present with lytic lesions in the bones with resulting bone pain and hypercalcemia, and renal insufficiency. They also have immunoglobulin light chains in the urine (Bence Jones proteinuria).

Question 22

The most common serum monoclonal antibody (M protein) is IgG, which is found in 55% of patients with MM. Rarely, cases of MM will be associated with IgM, IgD, and IgE. Other cells produced in the bone marrow may be reduced, resulting in anemia (fatigue) and decreased immune function (infection).

Elevated IgM and plasma cells are more likely associated with?

Answer 22

Waldenström macroglobulinemia, which can lead to hyperviscosity syndrome that may present as blurred vision or Raynaud phenomenon. B lymphoblasts, T lymphoblasts, and myeloblasts are immature precursors cells that do not secrete immunoglobulin. These are also not associated with the manifestations of renal injury, hypercalcemia, and increased fracture risk.

Question 23

This patient presents with near-constant joint pain and a history of multiple “flare-ups” of pain affecting his ankles, toes, and fingers. The recent development of nontender lesions on his ears and Achilles tendon suggests that this patient has a classic case of chronic gout. The intermittent attacks have given rise to disfiguring tophi (like those shown in the images).

Gout (also called gouty arthritis) is a common manifestation of hyperuricemia; tophi form as a result of the accumulation of monosodium urate crystals surrounded by reactive fibroblasts and chronic inflammatory cells in the joints and soft tissues. Unlike swelling in acute gout, tophi are nontender. Common extra-articular sites of tophus formation include?

Answer 23

the Achilles tendon and the helix of the external ear. Aspiration of a tophus usually reveals the presence of negatively birefringent needle-shaped crystals characteristic of gout.

In this patient, who has had multiple attacks of gout, treatment should focus both on pain relief and prevention of future attacks and development of additional extra-articular tophi. Allopurinol and febuxostat are the most effective treatments for chronic gouty arthritis and lower the levels of uric acid by blocking xanthine oxidase.

Question 24

The other answer choices would not be used in the prevention of gout attacks. Colchicine, which binds tubulin, and nonsteroidal anti-inflammatory drugs (NSAIDs), which block formation of prostaglandins and thromboxanes from arachidonic acid, are used in the treatment of acute attacks of gout but have no use in prevention of attacks. Corticosteroids inhibit?

Answer 24

the release of phospholipase A2 and have no use in prevention of gout attacks. COX-2 inhibitors selectively inhibit cyclooxygenase-2 and are not used in the treatment or prevention of gout.

Question 25

This patient presents with fatigue, vomiting, and abdominal distention as well as scleral icterus, jaundice, a palpable liver, and flapping tremor with wrist extension, all indicative of chronic liver disease. Imaging reveals a large lesion in the caudate lobe, which is suspicious for hepatocellular carcinoma. This patient most likely has macronodular liver cirrhosis (also known as stage IV fibrosis), characterized by bridging fibrosis with regenerative nodules, which has led to the development of?

Answer 25

a hepatocellular carcinoma.
In patients with chronic liver disease, vitamin K-dependent γ-carboxylation and synthesis of factors II, VII, IX, and X may be impaired, resulting in prolonged prothrombin time (extrinsic pathway). Because the international normalized ratio (INR) is calculated using the prothrombin time, it would also be elevated. Later, with further damage, partial thromboplastin time (intrinsic pathway) may also be affected.

Question 26

Although liver enzymes (eg, AST and ALT) are often elevated in chronic liver disease, they are not indicative of liver function and therefore not best representative of severity of organ involvement. Liver failure would not cause?

Answer 26

decreased estrogen levels, but rather would result in increased estrogen levels. Likewise, serum albumin levels would decrease, not increase, in chronic liver disease. Levels of von Willebrand factor and β-human chorionic gonadotropin levels are not generally affected by hepatocellular carcinoma or liver disease.

Question 27

This patient presents with recent onset seizures. A CT scan reveals a supratentorial, contrast-enhancing mass. The tumor does not invade the parenchyma, has a smooth demarcation, and originates next to the dura. These characteristics (seen on the CT image) are consistent with ?

Answer 27

meningioma.
Meningiomas arise from the arachnoid layer of the leptomeninges and are relatively benign, resectable tumors. The classic histologic characteristics are psammoma bodies or areas of calcification surrounded by concentric whorls. Other neoplasms that exhibit psammoma bodies are papillary thyroid carcinoma, serous papillary carcinoma of the ovary, and malignant mesothelioma.

Question 28

Undifferentiated tumor growth indicates anaplasia, a sign of aggressive malignancy. Neovascular proliferation is one of the defining characteristics of glioblastoma multiforme. Oligodendrogliomas have round nuclei with clear cytoplasm on histologic examination, and they primarily affect the frontal lobes. Craniopharyngioma, a pituitary tumor, contains?

Answer 28

embryonal cells that are remnants of Rathke’s pouch.

Question 29

The patient’s temporary right-sided hemiparesis is suggestive of a transient ischemic attack (TIA). Her signs and symptoms— bleeding from different parts of her body, throbbing and burning in her hands and feet, and an enlarged spleen—point to?

Answer 29

essential thrombocythemia, which the extraordinarily high platelet count confirms.
Essential thrombocythemia is a myeloproliferative disorder characterized by platelet overproduction by megakaryocytes; its cause is unknown. Patients exhibit epistaxis, thrombosis, bruising, bleeding, and mild splenomegaly. Patients also complain of erythromelalgia, which is burning and redness of the hands and feet caused by platelets obstructing blood flow in capillaries and arterioles. Older patients also may experience TIAs as a result of abnormal clotting.

Question 30

The preferred cytoreductive medication is hydroxyurea, an antineoplastic drug used to treat a wide variety of disorders from leukemia to sickle cell disease. Hydroxyurea interferes with DNA synthesis by inhibiting ribonucleotide reductase, preventing conversion of ribonucleotides to deoxyribonucleotides and thus decreasing the platelet count.

Both immune thrombocytopenia and thrombotic thrombocytopenic purpura are characterized by low platelet counts, in contrast to the extremely high platelet counts in essential thrombocythemia. Polycythemia vera causes?

Answer 30

increased production of WBCs, RBCs, and platelets and thus, massive hepatosplenomegaly. Patients with sickle cell disease are functionally asplenic, and their platelet counts are normal.