Flashcards in Hem n Onc 8-8 (10) Deck (29):
This patient presents with a polypoid exophytic mass on the wall of the cecum during a colonoscopy. The growth is positive for mucinous adenocarcinoma. This patient’s neoplasm was found in the cecum, which is located before the ascending colon and after the ileocecal valve.
Superior mesenteric lymph nodes receive lymph drainage from the jejunum, ileum, cecum, the cecal appendix, and the ascending and transverse parts of the colon. Thus, this patient’s neoplasm is most likely?
to spread to the superior mesenteric lymph nodes. To facilitate memorization of this anatomy, the lymph drainage follows the vascular supply of these regions. Embryologically, all foregut derivatives are supplied by the celiac trunk, midgut derivatives by superior mesenteric artery (SMA), and hindgut derivatives by inferior mesenteric artery (IMA). Because the cecum is a midgut derivative, it is supplied by the SMA; therefore, it is drained by the superior mesenteric group of lymph nodes.
It would be unlikely for this patient’s adenocarcinoma to spread first to the following groups of lymph nodes:
Celiac lymph nodes drain lymph fluid from the liver, spleen, pancreas and upper duodenum.
Inferior mesenteric lymph nodes drain lymph fluid from the descending colon, starting at the splenic flexure to the upper rectum and including the sigmoid colon.
Internal iliac lymph nodes drain lymph fluid from the lower rectum to the anal canal (above the pectinate line), bladder, vagina (middle third), cervix, and prostate.
Superficial inguinal lymph nodes drain lymph fluid from ?
the anal canal (below the pectinate line), skin below the umbilicus (except the popliteal area), scrotum, and vulva.
Recent-onset headache and bitemporal hemianopia, in combination with imaging showing a calcified cyst in the suprasellar region, are classic for craniopharyngioma. Craniopharyngioma is the most common supratentorial tumor in children and is derived from remnants of Rathke’s pouch. Rathke’s pouch gives rise to the anterior pituitary gland, and deficiencies of the anterior pituitary hormones, such as growth hormone, are responsible for the symptoms of growth failure, hypothyroidism, and diabetes insipidus often seen in these patients.
As the tumor grows, it compresses the optic chiasm (resulting in bilateral hemianopia) and causes ?
headache. Bilateral hemianopia and headache are also presenting signs of a pituitary adenoma, such as a prolactinoma. In contrast to craniopharyngioma, prolactinomas are associated with increased levels of hormones such as prolactin, leading to hypogonadism and galactorrhea. The table compares the characteristics of craniopharyngiomas versus pituitary adenomas. Be careful not to confuse them!
Patients with craniopharyngioma may also have decreased levels of other anterior pituitary hormones, including thyroid-stimulating hormone and luteinizing hormone; consequently, testosterone and thyroid hormone levels may be decreased, not increased.
Although dopamine inhibits prolactin secretion, the craniopharyngioma impedes delivery of dopamine to the anterior pituitary; therefore, the prolactin level is more likely to be increased in this patient, not decreased.
The release of aldosterone is regulated by ?
the renal-angiotensin-aldosterone system, not the anterior pituitary. Thus, aldosterone is not likely to be affected by the presence of a craniopharyngioma.
The patient is a 65-year-old immigrant from Africa who has been experiencing episodes of hematuria over the past several months. He presented at the emergency department following an episode of gross hematuria.
A physical examination finds mild hepatosplenomegaly, and urinalysis is positive for blood. A CT urogram shows a large filling defect in the bladder, and a beside cystoscopy reveals a large fungating mass is seen adherent to the superior part of the bladder. A biopsy of the mass shows?
keratin pearl formation (indicated by the arrows in this image), a common finding in squamous cell cancers. Squamous cell carcinoma can be distinguished from transitional cell carcinoma pathologically by its appearance.
This patient is suffering from squamous cell carcinoma (SCC) of the bladder. Although this condition is rare in the United States, it is the most common type of bladder cancer in the world, accounting for 95% of cases. The most common cause is chronic irritation by the eggs of the helminth Schistosoma haematobium, which lodge in the bladder wall.
Countries in which Schistosoma haematobium is endemic have much higher rates of SCC of the bladder, and the organism is prevalent in many countries in sub-Saharan Africa.
Cigarette smoking is the most common risk factor for transitional cell carcinoma of the bladder, which is more common the United States than SCC of the bladder. Although cigarette smoking has also been linked to an increased risk of SCC of the bladder, the fact that this patient is originally from Kenya suggests helminth infection is the more likely risk factor.
Aniline dye exposure is also associated with?
transitional cell bladder carcinoma, but is not associated with SCC of the bladder. The association with human papillomavirus infection and bladder cancer remains unclear; this infection is mostly implicated in cervical carcinoma.
Although long-term catheterization can cause irritation that predisposes to squamous cell carcinoma, there is no indication that this patient had an indwelling catheter at any time.
To answer this question, you must understand that microtubule assembly/disassembly is a critical process that occurs during mitosis (M phase of the cell cycle); if this process is blocked, cell division will stop. The vinca alkaloids (vincristine and vinblastine) exert their effect specifically through the inhibition of microtubule function and spindle formation, which are critical to mitosis. In contrast,?
taxanes (paclitaxel and docetaxel) reversibly bind to tubulin and hyperstabilizes microtubules that have already polymerized, preventing spindle breakdown.
The other pairs of drugs listed are not both specific M-phase inhibitors. 5-Flourouracil, 6-mercaptopurine, and methotrexate are specific S-phase inhibitors, whereas bleomycin is a G2-phase inhibitor. Both cyclophosphamide and busulfan are cell cycle nonspecific.
This patient presents with a nodule in the left lobe of her thyroid but has no tremor, restlessness, heat intolerance or increased anxiety. The histologic image provided with the vignette shows a psammoma body, a concentrically calcified lamellated inclusion. The image here shows cells with cleared-out nuclei with no chromatin in the center, known as "Orphan Annie" eyes. These histologic findings are characteristic of papillary carcinoma of the thyroid.
Papillary carcinoma is the most common form of ?
thyroid cancer. A major risk factor for the development of these cancers is a history of ionizing radiation to the neck. These cancers typically appear as cold lesions on a scintiscan.
Follicular and medullary carcinomas of the thyroid, goiter, and thyroglossal duct cysts are not associated with the finding of psammoma bodies on histologic examination. Nontoxic goiter does not result from a neoplastic process. A thyroglossal duct cyst would present as a ?
midline lesion and would not be localized to one lobe.
A 72-year-old Caucasian man undergoes hip surgery. On his third hospital day, he develops chest pain, tachycardia, dyspnea, and a low-grade fever. The man goes into cardiac arrest and efforts to resuscitate him are unsuccessful. On autopsy a massive pulmonary embolus is discovered.
Which of the following would most likely predispose the patient to this event?
Mutation in the factor V gene
A mutation in the factor V gene, also known as factor V Leiden, causes resistance to deactivation of factor V by protein C. Uninhibited factor V activity leads to a hypercoagulable state, which predisposes to deep vein thrombosis (DVT) and subsequent pulmonary embolism (PE). Factor V Leiden mutation is the most common cause of inherited thrombophilia and is most commonly found in Caucasian individuals. However, having a non-Caucasian patient should not exclude factor V Leiden when all other signs point to the disease, as it has been found in people of varying ethnicities. Clinical signs of PE include tachycardia, tachypnea, and low-grade fever, though many patients with PE are asymptomatic.
Factor VIII deficiency (hemophilia A) would predispose an individual to bleeding. Factor VIII is an integral part of the intrinsic coagulation cascade.
High, rather than low, homocysteine levels are associated with a hypercoagulable state. Though the mechanism remains unclear, promotion of thrombotic factors, adhesion molecules, platelet reactivity, and inhibition of fibrinolysis have been implicated.
[ D ] [ 10% ]
Proteins C and S act as negative regulators of the coagulation cascade. Therefore a deficiency, rather than overproduction, will lead to?
a hypercoagulable state.
[ E ] [ 4% ]
von Willebrand factor allows platelets to adhere to a defect where collagen is exposed and binds inactive factor VIII in circulation. A deficiency (von Willebrand disease) leads to bleeding complications such as epistaxis, menorrhagia, and gastrointestinal bleeds.
This patient presented with right foot pain and was found to have a thrombus in her popliteal vein. A positive Homan sign (pain on dorsiflexion on the foot) on physical exam is a classic finding for deep venous thrombosis (DVT). In conjunction with the other findings of malar rash (seen in the vignette image), joint pain, oral ulcers, anemia (decreased hemoglobin), and renal disease (elevated creatinine), this patient likely has undiagnosed systemic lupus erythematosus.
Patients with lupus are at risk of developing acquired antiphospholipid antibody syndrome caused by the lupus anticoagulant. Lupus anticoagulant is an IgM or IgG antibody that binds platelet phospholipids. Platelet phospholipids are required for both the intrinsic and extrinsic clotting pathways. Antiphospholipid antibodies bind to platelet phospholipids, thereby making them accessible to clotting factors and leading to recurrent venous and arterial thrombosis. Because the partial thromboplastin time (PTT) assays use exogenous phospholipids, the antibodies inhibit?
their function and paradoxically show an increase in coagulation time (hence the name lupus anticoagulant). Although antiphospholipid syndrome often manifests with a normal platelet count, this patient has systemic lupus erythematosus, which is often associated with thrombocytopenia. Lupus anticoagulant is also associated with recurrent miscarriage as well as false positive syphilis tests.
Factor VIII antibodies result in increased bleeding (similar to hemophilia A), not increased clotting as seen in this patient, and would cause a prolonged PT and PTT.
Heparin antibodies target heparin but can also cross-react with and destroy platelets; the inactivated heparin results in a hypercoagulable state, with no PT/PTT prolongation.
GpIIb/IIIa antibodies target platelets and lead to?
idiopathic thrombocytopenic purpura (ITP), which is associated with normal a PT/PTT.
RBC antibodies lead to hemolytic anemia, in which signs of increased RBC breakdown such as jaundice and elevated bilirubin may be seen.
This patient presents with microangiopathic hemolytic anemia (MAHA), thrombocytopenia, neurologic and renal abnormalities, and fever, which represent the classic pentad of thrombotic thrombocytopenic purpura (TTP). Patients with TTP have large multimers of von Willebrand factor (vWF) because there is a deficiency of the metalloprotease that breaks down the ultralarge vWF multimers. This metalloprotease is ADAMTS13, and autoantibodies against it can usually be isolated from the plasma of a patient with the acquired form of TTP.
The hallmark findings of TTP are MAHA and thrombocytopenia. The presence of ultralarge vWF multimers leads to?
intravascular platelet aggregation, creating partially thrombosed vessels. As RBCs are forced through this narrowed lumen they are exposed to high shear forces, which leads to intravascular hemolysis and the formation of schistocytes (fragmented RBCs seen in the patient's blood smear). Thrombocytopenia results from deposition of platelets in microthrombi. Neurologic findings may be seen with TTP, with subtle manifestations such as headaches and confusion being common. Transient focal neurologic findings may be seen, and some patients may have seizures or be comatose. Renal insufficiency is usually mild, and renal failure is rare. TTP should be suspected if MAHA and thrombocytopenia are present.
Levels of other proteins in the answers choices would not be used to diagnose TTP:
Clotting factor levels would be used to diagnose hemophilia A and B, which are deficiencies in factors VIII and IX, respectively.
Cytoskeletal protein deficiencies (ankyrin, spectrin) lead to hereditary spherocytosis (HS).
Pyruvate kinase deficiency is an example of inherited kinase deficiency, leading to?
ATP deficiency in RBCs and, as a consequence, hemolytic anemia.
Shiga toxin hemolytic-uremic syndrome (ST-HUS) stems from a bacterial toxin and is more commonly seen in children. ST-HUS is associated with a prominent gastrointestinal prodrome of abdominal pain, nausea, vomiting, and diarrhea (often bloody). HUS and TTP are both caused by insults that lead to excessive activation of platelets which deposit as thrombi in the microcirculatory beds.
This is a hard question, and it’s going to test how well you understand the math and the formulas that underlie epidemiology.
First, realize that hereditary spherocytosis is an autosomal dominant disorder. Based on Hardy-Weinberg assumptions regarding the distribution of the disease-causing allele in this population, the prevalence of this disease can be calculated using the formula:
p2 + 2pq + q2 = 1
p is the frequency of A (dominant allele), or in other words, the frequency of the disease-causing allele, which in this case is 0.2.
q is the frequency of a (recessive allele), calculated as: 1 – 0.2 = 0.8.
2pq is the frequency of heterozygosity (Aa), or the carrier frequency; in this case, 2 × 0.2 × 0.8 = 0.32.
Let’s construct a 2 × 2 table using this information and the stated false-positive (FP) and false-negative (FN) rates. We know the FN rate is 0, and the FP rate is 10 (red numbers in the table).
So how do we get the values for the rest of the table entries?
We know that hereditary spherocytosis is autosomal dominant, meaning that anyone with AA or Aa will be affected. We can calculate the number of true positives (TP) as:
AA + Aa = p2 + 2pq = 0.04 + 0.32 = 0.36
This means that 36% of 250 individuals, or 90 people, will have the disease.
And since 90 people have the disease, 250 – 90, or 160, do not have the disease (which includes FP and true negative [TN] results). Now our table is complete and the math cross-checks.
So now we can calculate the positive predictive value (PPV) and answer this question:
PPV = TP / (TP + FP)
PPV = 90 / (90 + 10)
= 90 / 100
= 0.9, or 90%
The PPV is 80% if the prevalence of the disease is 0.2. However, in this scenario, it is the frequency of the disease-causing allele that is 0.2, not the prevalence. For an allele frequency of 0.2, the prevalence of an autosomal disorder is 36%.
If the disorder were recessive, 40% would be the expected answer. However, we know that hereditary spherocytosis is autosomal dominant. Only if the disease prevalence were 4% would the PPV be 40%.
PrevalenceHereditary spherocytosisAutosomal dominant
[ D ] [ 13% ]
It is the specificity of the test that is 94%, rather than the PPV. You can calculate this number by using the formula: specificity = 1 – FP rate.
Sensitivity and specificity
[ E ] [ 9% ]
The sensitivity of the test is 100%, not the PPV. The sensitivity is 100% because?
there are zero FN results. The formula for calculating the sensitivity is: sensitivity = 1 – FN.
Cyclophosphamide is a chemotherapeutic DNA alkylating agent. Adverse effects include myelosuppression and hemorrhagic cystitis. The excessive number of RBCs in this patient’s urine indicates that she has hemorrhagic cystitis (a normal result is =2 RBCs/hpf). It is also not uncommon to find protein in the urine with this condition. A urinary tract infection may be ruled out in this patient because of the few WBCs and negative leukocyte esterase and nitrite tests.
Hemorrhagic cystitis in patients taking cyclophosphamide can be prevented with?
mesna. Mesna binds to cyclophosphamide metabolites in the urine and neutralizes them.
Trimethoprim-sulfamethoxazole is an antibiotic used to treat urinary tract infections. Protamine sulfate treats acute overheparinization. And the other drugs listed are used to mitigate the side effects of other anticancer drugs:
the myelosuppression associated with methotrexate
Dexrazoxane prevents the cardiotoxic effects of anthracyclines
Amifostine prevents cisplatin-induced nephrotoxicity
A 32-year-old man who is HIV-positive develops multiple Kaposi's sarcoma lesions on his skin. The patient wants to know how he acquired these lesions, and the physician explains that exposure to viruses is sometimes linked with the development of specific cancer types. The patient asks if there is a vaccination available to protect him from contracting other viruses that are linked with cancer.
Which of the following virus-cancer associations is the correct pairing and can be effectively prevented by the administration of a vaccination?
Hepatitis B/hepatocellular carcinoma
Recombinant hepatitis B (HBV) vaccine protects against HBV infection and prevents the future development of primary hepatocellular carcinoma associated with HBV infection. HBV can cause both acute and chronic disease. Acute phase HBV infection can be asymptomatic or fulminant. Chronic phase HBV infection is usually asymptomatic and may progress to cirrhosis or hepatocellular carcinoma. Notably, human papillomavirus (HPV) has been identified as the causative agent in cervical cancer and other anogenital cancers. The recent development of a vaccine against four of the major types of HPV will, it is hoped, decrease the rate of cervical cancer in the future.
Epstein-Barr virus (EBV), the primary cause of infectious mononucleosis, is a herpesvirus that has been detected in nasopharyngeal carcinoma cells and in Burkitt's lymphoma. There is no vaccine for EBV.
EBVVaccineEpstein-Barr virusInfectious mononucleosisHerpesviridaeNasopharyngeal carcinomaBurkitt's lymphoma
[ C ] [ 11% ]
Hepatitis C infections are also implicated in hepatocellular carcinoma. There is currently no vaccine for the hepatitis C virus, although many research studies are under way to develop such a vaccine.
VaccineH2B.1BHepatocellular carcinomaHepatitis C virus
[ D ] [ 6% ]
Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus that has been associated?
with adult T-cell leukemia/lymphoma and HTLV-1-associated myelopathy. There is no vaccine for HTLV-1.
VirusType 1RetrovirusAdultLymphomaMyelopathyVaccineT-cell leukemia
[ E ] [ 7% ]
Human papilloma virus (HPV) has been associated with cervical cancer, not Kaposi's sarcoma, which is caused by human herpesvirus-8 infection (HHV-8) There is a vaccine against the major cancer-causing strains of HPV , but there is no vaccine for HHV-8.
HPVVaccineStrainHuman papilloma virusCervical cancerKaposi's sarcomaHuman Herpesvirus 8 infection
This patient is diagnosed with an acute upper respiratory viral infection. Interleukin-6 is a proinflammatory cytokine and is known to induce acute-phase protein synthesis. It is produced predominantly by T-cells (Th2), but also by macrophages. Acute-phase proteins are produced by?
the liver in response to inflammation. In addition to interleukin-6, other common positive acute-phase proteins that increase in plasma concentration are interleukin-1, interleukin-8, and TNF-α.
Interleukin-10 (IL-10) is an anti-inflammatory cytokine that is often produced by monocytes and regulatory T cells.
Interleukin-2 (IL-2) is a T-lymphocyte growth factor produced by Th cells and stimulates the growth of helper and cytotoxic T cells.
Interleukin-5 (IL-5) stimulates ?
B-lymphocyte growth, immunoglobulin secretion growth, and differentiation of eosinophils.
Interleukin-9 (IL-9) is produced by T lymphocytes and plays a role in mast cell activation.
This patient presents with a dozen small, bumpy prominences on his upper back and shoulders, an unusual freckling pattern in his axilla and groin area and areas of hyperpigmentation on his upper arms and lower back. These features describe neurofibromatosis type 1 (NF-1), characterized by neurofibromas, café-au-lait spots (seen in the stem image), and Lisch nodules, which are yellow-brown pigmented nodules on the iris (seen here).
Neurofibromatosis type 1 is caused by?
the loss of both copies of the NF-1 tumor suppressor gene on chromosome 17q. In these cases, mutations in one NF-1 gene is inherited, and the second mutation in the NF gene is acquired in some cells.The loss of function in the NF-1 gene results in this patient’s neurofibromatosis.
Neurofibromatosis type 2, which is less likely to present with cutaneous signs compared to type 1, may manifest in cranial nerve VIII schwannomas. Furthermore, NF-2 is associated with misproduction of the gene product merlin. NF-1 is due to mutations of the NF-1 tumor suppressor gene on chromosome 17q, and it is?
not related to p53 mutations or increased proto-oncogene production.
Neurofibromatosis type 1 is characterized by neurofibromas, café-au-lait spots, and Lisch nodules, which are?
pigmented nodules on the iris.
The patient is being treated for her triple-negative ductal breast cancer with a chemotherapeutic regimen including paclitaxel, which puts her at risk of drug-induced myelosuppression. The development of a persistent fever in this patient strongly indicates that she has an ?
Infection secondary to neutropenia. To address this, her physician added granulocyte colony-stimulating factor (G-CSF) to her existing drug regimen.
G-CSF receptor is present on the surface of granulocyte precursors in bone marrow, and its activation stimulates granulocyte (white blood cell) proliferation. CD34 is a marker found on pluripotent stem cells.
G-CSF is used to stimulate granulocyte production in patients with neutropenia, and acts by binding and activating pluripotent hematopoietic stem cells. Pluripotent hematopoietic stem cells are?
CD34+ and CD38-, and have the capacity to differentiate into erythroblasts and myeloblasts in response to biochemical stimuli.