Hem n Onc 8-8 (9) Flashcards
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.
