Flashcards in Hem n Onc 8-8 (9) Deck (30):
This patient's nonspecific symptoms of fever, rash, and bone swelling, as well as the skin rash are suggestive of the systemic disease Langerhans cell histiocytosis (formerly known as histiocytosis X). It is more common in children from birth to 15 years, and its prevalence appears to be higher among Caucasians. Its frequency is greater in males than in females, with a male-to-female ratio of 2:1.
Diagnosis is confirmed on biopsy of affected tissues, which shows proliferation of histiocytes, which are cells with grainy, eosinophilic cytoplasm, and distinct cell margins (shown in the vignette image). The term “histiocyte” is equivalent to “macrophage,” which is a cell of the innate immune system that ?
phagocytoses cell debris, infected cells, and pathogens.
Specific types of macrophages reside in certain tissues, including Kupffer cells in the liver, alveolar macrophages in the lungs, Langerhans cells in the skin, and dendritic cells in the skin and lymph nodes.
Granulocyte precursors include promyelocytes, myeloblasts, and band cells, seen typically in leukemias such as acute myelogenous leukemia (AML), which manifests with bone marrow failure in older patients.
Malignancies of CD4+ lymphocytes—which costimulate B lymphocytes—are rare. The human T-lymphotropic virus type 1 (HTLV-1) can cause adult T-cell leukemia/lymphoma (ATLL), which is associated with lytic bone lesions and lymphadenopathy.
Mast cells are responsible for?
releasing histamine. Mastocytosis is a rare tumor of mast cells leading to cutaneous symptoms such as itching and hyperpigmentation.
Mature B-cells—plasma cells—secrete antibodies. Multiple myeloma is a B-cell neoplasia leading to CRAB findings: hyperCalcemia, Renal damage, Anemia, and lytic Bone lesion
This patient presents with recent-onset, severe fatigue and breathlessness upon exertion. Physical exam is remarkable for multiple ecchymoses. His blood smear shows a blast with innumerable needle-like cytoplasmic inclusions called Auer rods (see image). This finding is diagnostic of acute promyelocytic leukemia (APL).
The granules in the promyelocytes in APL contain strong procoagulant substances. If these cells are disrupted, the granules pour out into the blood and can initiate coagulation, leading to?
disseminated intravascular coagulation (DIC). This is a common (and often fatal) side effect when traditional chemotherapy drugs are used in APL, as these drugs cause the malignant promyelocytes to burst open in the circulation, releasing their procoagulant substances and initiating widespread clotting.
The other lab findings are characteristic of liver cirrhosis (answer B), von Willebrand disease (answer C), immune thrombocytopenic purpura (answer D), and hemophilia A (answer E). In particular, coagulation tests can be very helpful in distinguishing TTP/HUS from DIC. In both TTP and HUS, platelets are activated without involvement of ?
the coagulation cascade, so the PT, PTT and plasma fibrinogen levels are normal; but in DIC they are all increased.
Acute promyelocytic leukemia is characterized by the presence of promyelocytes with many cytoplasmic Auer rods. Without proper treatment, patients with APL are at high risk for?
bleeding due to DIC, which is characterized by a prolonged PT/INR and PTT and a decreased platelet count.
This patient presents with agitation, personality changes, and chronic headache. After head CT, he is diagnosed with a slow-growing tumor located in the right frontal lobe of his brain. Based on these findings and the histology of the tumor, the diagnosis is oligodendroglioma. Oligodendrogliomas are relatively benign tumors that primarily affect the frontal lobes of adults and have a tendency to calcify. Symptoms include seizures, headache, personality changes, and neurologic deficits.
The classic histologic appearance of oligodendroglioma is?
“fried eggs” with perinuclear halos and “chicken wire” capillary patterning. Oligodendrogliomas are derived from oligodendrocytes, which normally function to myelinate the central nervous system (CNS).
Glioblastoma multiforme is derived from astrocytes, which normally function to provide structural and metabolic support for neurons. The hypothalamus and pituitary gland are responsible for hormone regulation. Microglia cells carry out phagocytosis in the central and peripheral nervous system. Meningeal cells are tightly packed to provide protective layering of the central nervous system. Vascular endothelial cells help form ?
the epithelial lining of the interior surface of small blood vessels, including cerebral vessels.
This patient is encouraged by his wife to seek medical attention for the very dark urine he’s been producing over the past 4 days. The results of the flow cytometry tests, which are used to determine the absence of specific RBC or WBC cell surface proteins (CD59+ and CD55+), indicate that ?
the patient has paroxysmal nocturnal hemoglobinuria (PNH), a rare disease caused by acquired mutations in the PIG-A glycosyl phosphatidylinositol (GPI) anchor.
Paroxysmal nocturnal hemoglobinuria is a rare acquired disorder caused by PIG-A GPI anchor mutation, which leads to?
intravascular hemolysis and hemosiderin in the urine.
Elevated branched-chain ketoacids are seen in maple syrup urine disease, the colloquial name for elevated branched-chain ketoaciduria. It results in sweet-smelling urine that is dark. Infants can have seizures, hypoglycemia, and metabolic acidosis.
Factor V Leiden causes a resistance to protein C, producing an abnormal activated protein C resistance test. This leads to easier thrombus formation, but not a microcytic anemia or thrombocytopenia.
Elevated urine homogentisic acid is associated with?
alkaptonuria, which results in arthritis and darkened urine (after it is left to stand) from a deficiency of homogentisic oxidase.
IgG, IgM, and C3 deposition along glomerular basement membrane would be seen in poststreptococcal glomerulonephritis, which typically occurs 2 weeks after a Streptococcus pyogenes infection. It manifests with dark urine, but no anemia, thrombosis, or thrombocytopenia.
This patient has xeroderma pigmentosum, a disease characterized by extreme sensitivity to sunlight, skin damage, and a predisposition to malignancies such as melanoma. The disease results from a defect in the nucleotide excision repair machinary required for the repair of pyrimidine dimers in response to ultraviolet light exposure. Nucleotide excision repair is a different mechanism from base excision repair. Base excision repair occurs in response to the spontaneous or toxic-dependent deamination. Nucleotide excision repair is?
mediated by specific endonucleases that release the oligonucleotides containing the damaged bases and allow the DNA polymerase and ligase to fill the gap.
A defect in proofreading enzymes would not cause xeroderma pigmentosum. It would affect DNA replication in all body tissues, not just those exposed to UV light.
The mismatch repair mechanism replaces segments of DNA that include mismatched bases. Hereditary nonpolyposis colorectal cancer is caused by defects in mismatch repair.
ReplaceDNABasesMismatch repairHereditary nonpolyposis colorectal cancer
[ D ] [ 3% ]
Ionizing radiation, such as X-rays, removes electrons from atoms and molecules such as DNA. This causes?
chromosome breakage, translocations, and point mutations. Bloom syndrome and ataxia-telangiectasia are rare autosomal recessive genetic disorders that are ? hypersensitive to ionizing radiation. Patients with xeroderma pigmentosum are hypersensitive to UV light.
Xeroderma pigmentosum is an autosomal recessive disorder caused by a defect in nucleotide excision repair, which impairs a cell's ability to repair damage induced by ultraviolet radiation. This condition leads to melanoma and nonmelanoma skin cancers at an early age. It is managed by?
reducing sun exposure and destruction/excision of early skin cancers.
This patient’s presentation of weakness and fever with a rash, along with the findings of the lab tests and blood smear, describe acute lymphoblastic leukemia (ALL). It manifests as a rapid onset of bone marrow suppression, including anemia (eg, weakness), thrombocytopenia (eg, petechiae), and susceptibility to infection. Peripheral blood smear and bone marrow show numerous lymphoblasts.
Patients with Down syndrome (DS) are at elevated risks of both acute myeloid leukemia (AML) and ALL. However, ALL is more common than AML in children. Pediatric patients with DS-ALL have an?
inferior outcome compared with non-DS patients due to higher treatment-related mortality and a higher relapse rate.
Immune thrombocytopenic purpura occurs after an upper respiratory infection presenting with petechiae or purpura with no systemic symptoms, often occurs in young children, and may not require treatment.
Epstein-Barr infection is associated with cancers such as Hodgkin lymphoma and nasopharyngeal carcinoma but not ALL.
HIV is associated with?
non-Hodgkin lymphoma and Kaposi sarcoma.
Turner syndrome is a 45,XO genotype that does not have any association with ALL.
Taxanes (including paclitaxel) are a group of drugs that inhibit mitosis by stabilizing microtubules in the polymerized state, thus inhibiting their breakdown. The main adverse effects of taxanes are?
myelosuppression, alopecia, and hypersensitivity reactions.
The other drugs have mechanisms of action different from taxanes. Bleomycin is a DNA intercalator that produces reactive oxidative species to damage DNA. Cisplatin is an alkylating agent that forms DNA cross-linking and prevents cell cycle progression. Both colchicine and vincristine inhibit microtubule formation.
Many anticancer drugs act by inhibiting microtubule function via stabilization of formed polymers, such as taxanes like paclitaxel; or by inhibition of polymerization, which is?
the mechanism of drugs like vincristine and colchicine.
The patient presents with a progressive course of a disease whose symptoms include lower extremity weakness, back pain, and urinary incontinence. In addition, he has skin lesions affecting his scalp, axillae, and groin. These symptoms indicate an infection with human T-cell lymphotropic virus (HTLV-1).
Human T-cell lymphotropic virus (HTLV-1) is an oncogenic virus that causes both adult T-lymphocyte leukemia and HTLV-1-associated myelopathy, also known as tropical spastic paraparesis, involving demyelination. Common manifestations of adult T-lymphocyte leukemia are?
skin lesions and lytic bone lesions, which can lead to hypercalcemia (as reflected in this patient’s measured calcium level of 13.6). HTLV-1 myelopathy is characterized by myelin destruction within the spinal cord and periventricular regions of the brain. Patients have a progressive course that includes lower extremity weakness, back pain, urinary incontinence, and eventual spastic paraplegia. Cranial nerves and cognitive function often remain intact.
The other viruses are not associated with HTLV-1. Hepatitis B virus (HBV) is associated with hepatocellular carcinoma. Human herpesvirus-8 is associated with Kaposi sarcoma. Human papillomavirus (HPV) is associated with cervical carcinoma. JC virus is associated with?
progressive multifocal leukoencephalopathy (PML).
This patient has pernicious anemia, which is a failure of the body to absorb cobalamin from the diet and usually develops after the age of 40 years. Patients present with symptoms of vitamin B12 deficiency, with an insidious onset of neurologic symptoms, including weakness, ataxia, dementia, and psychosis. A complete blood cell count will show a megaloblastic anemia. Cobalamin can be absorbed only when bound to intrinsic factor (IF), through receptors in the distal ileum. The Schilling test for pernicious anemia will determine whether the problem lies in the combination of IF with cobalamin or in the absorption of this complex in the ileum. In this patient, the repeat dose showing?
high levels of radioactive vitamin B12 indicates that he has no problem with absorption. Thus, this patient has type I, or "blocking," antibody.
In this patient, the repeat dose in his Schilling test shows high levels of radioactive vitamin B12 in his urine 24 hours later. This indicates that he has no problem with absorption, but has a problem with the combination of intrinsic factor (IF) with cobalamin. This is due to an autoimmune antibody against IF-producing cells, which decreases the level of IF, thereby decreasing cobalamin absorption. A direct antibody to cobalamin has not been characterized in these patients.
Schilling testVitaminCombinationIntrinsic factorCobalamin(1+)AutoimmuneAntibody
The Schilling test indicates that this patient has a problem with IF binding to cobalamin, rather than absorption of the complex. If the repeat dose had also resulted in ?
low radioactivity, then he would have the type II, or "binding," antibody.
The cause for this patient's pernicious anemia does not lie in intrinsic factor (IF)-cobalamin absorption, but rather is due to the combination of IF with cobalamin. Additionally, receptors for this complex are found only in the distal ileum, and not in the jejunum.
This patient does not have a problem in IF-cobalamin absorption. Additionally, receptors for this complex are found only in the distal ileum and would not be found in the duodenum.
The patient is presenting with an altered mental status, fever, and jaundice, in conjunction with multiple lab values concerning for anemia, thrombocytopenia, and renal dysfunction. Examination of the blood smear reveals schistocytes (indicated in this image by the arrows). The overall clinical picture strongly suggests the patient is presenting with thrombotic thrombocytopenic purpura (TTP).
She exhibits the classic pentad of TTP: central nervous system manifestations, renal insufficiency, fever, thrombocytopenia, and microangiopathic hemolytic anemia (MAHA). Hemolysis is identified by ?
elevated levels of lactate dehydrogenase and indirect bilirubin, and the blood smear contains schistocytes, which are RBCs that are mechanically cleaved in the microvasculature. The normal von Willebrand factor (vWF) protease ADAMTS13 is absent or decreased in patients with TTP, often as a result of autoantibody-mediated enzyme inhibition or, occasionally, genetic mutations.
Antibodies directed against platelets are found in immune thrombocytopenic purpura (ITP), which results in an isolated thrombocytopenia and large platelets on peripheral smear.
Sickle cell disease is an inherited disorder of hemoglobin, resulting in crescent-shaped cells on the blood smear.
Mutations affecting the erythrocyte membrane are found in hereditary spherocytosis, which results in extravascular hemolysis and spherocytes on peripheral blood smear.
A viral infection of hepatic cells is found in?
several types of infections, including cytomegalovirus and hepatitis A, B, and C. It may result in jaundice and elevated liver enzyme levels.
Based on this patient’s history of HIV without proper medical management and presentation of purple macules and papules, he most likely has Kaposi sarcoma (KS). KS is caused by the double-stranded DNA human herpesvirus (HHV) 8, and is considered an AIDS-defining illness.
Of the answer choices, only ?
roseola infantum is caused by another member of the human herpesvirus family, HHV-6. Other members of the herpesvirus family are: herpes simplex virus-1 and herpes simplex virus-2 (oral and genital lesions), Epstein-Barr virus (mononucleosis and Burkitt lymphoma), cytomegalovirus (mononucleosis), and varicella-zoster virus (chickenpox and shingles).
Hepatitis C belongs to the flavivirus family.
Hepatitis B belongs to the hepadnavirus family.
Molluscum contagiosum is caused by poxvirus which is part of the poxviridae family.
Cervical cancer is most likely caused by?
human papillomavirus (HPV) from the papillomavirus family.
This patient’s week-long flu-like symptoms, combined with his enlarged cervical lymph nodes and spleen, are a classic presentation of infectious mononucleosis, a disease caused by the Epstein-Barr virus (EBV). EBV is a member of the herpesvirus family and is characterized by linear double-stranded enveloped DNA. Herpesviruses are unique in that they are the only viruses that obtain an?
envelope via budding from the nuclear membrane.An example of a linear double-stranded DNA virus without an envelope is adenovirus, which causes conjunctivitis and respiratory tract infections. The only linear double-stranded RNA viruses without an envelope are reoviruses, which include coltivirus (which causes Colorado tick fever) and rotavirus (which causes gastroenteritis). A linear single-stranded RNA virus without an envelope would be a member of the family Picornaviridae, such as the hepatitis A virus. An example of a segmented single-stranded RNA virus with an envelope is orthomyxovirus, which causes influenza.
This patient recently received a bone marrow transplant, and over the course of several weeks developed a rash and diarrhea. This should raise suspicion for graft-versus-host disease GVHD. GVHD is an adverse effect of bone marrow transplantation, in which alloreactive donor T lymphocytes recognize the recipient as foreign and mount an immune response. The organs most often affected are the gut, skin, and liver, as evidenced by the rash, diarrhea, elevated alkaline phosphatase, elevated transaminases, and elevated LDH in this case. Human leukocyte antigen (HLA) matching of the donor and recipient can help reduce?
the severity of GVHD, but the disease may still occur due to a minor histocompatibility mismatch.
Acute graft rejection occurs when the recipient’s cytotoxic T-lymphocytes destroy the graft within weeks to months of the transplant.
Hyperacute graft rejection results in vessel occlusion, ischemia, or fibrinoid necrosis, occurs within minutes to hours after a transplant, and does not typically feature rashes or watery diarrhea.
Chronic organ rejection features donor peptides being displayed by?
recipient antigen-presenting cells, resulting in interstitial fibrosis, atherosclerosis, and vanishing bile duct syndrome, not symptoms seen in this patient.
Epstein-Barr virus, a member of the Herpesviridae family, is a double-stranded linear DNA virus that has been causally linked to a number of malignancies, including nasopharyngeal carcinoma, Burkitt lymphoma, and tumors in HIV-infected patients (non-Hodgkin lymphoma, for example).
Human papillomavirus, a double-stranded circular DNA virus, is associated with?
cervical cancer. Human T-lymphotropic virus 1 (HTLV-1), a single-stranded linear RNA virus, is associated with adult T-lymphocyte leukemia.