Pathology ABP Exam Question Bank

60 CME / SAM Credits


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Pathology Sample Questions:

Question 1

A 76­ year­ old man with a past medical history of AML presented with profound weakness, cough, and abnormal CBC. Bone marrow biopsy revealed 50% blasts and was consistent with acute monocytic leukemia. G­banding revealed normal karyotype, and molecular studies using next generation sequencing showed that he had FLT3­ITD, DNM­T3A, and NPM­1 mutations. Which of the following statements regarding the molecular studies are most accurate?

A) DNM­T3A is associated with higher disease burden, worse outcomes and by itself warrants more aggressive treatment.
B) ​FLT3­ITD encodes a DNA methyltransferase which catalyzes the addition of a methyl group to CpG islands resulting in reduced expression of downstream genes.
C) ​FLT3­ITD mutations alone are generally associated with a better outcome in cytogenetically normal cases.
D) Mutations resulting in NPM­1 activation result in possible internal tandem duplications or tyrosine kinase domain point mutations
E) ​A portion of the risk of having DNM­T3A and FLT2 mutations is mitigated by having a concurrent NPM­1 mutation

Answer
A) DNM­T3A is associated with higher disease burden, worse outcomes and by itself warrants more aggressive treatment.


Explanation
Correct: (A) DNM­T3A is associated with higher disease burden, worse outcomes and by itself warrants more aggressive treatment. Explanation: DNM­T3A is associated with higher disease burden, worse outcomes and by itself warrants more aggressive treatment. Explanation: In the classification of risk for AML through molecular testing, importance has been placed on NPM1 and FLT3, yet not much emphasis is given to DNMT3A mutations. DNMT3A has a known "domino effect" when it is combined with FLT­3 and NPM­1 mutations, particularly in the absence of those recurrent cytogenetic abnormalities seen in AML. DNM­T3A (not FLT3­ITD, choice B​) encodes a DNA methyltransferase which catalyzes the addition of a methyl group to CpG islands resulting in reduced expression of downstream genes. NPM­1 (not FLT3­ITD, choice C​) mutations alone are generally associated with a better outcome in cytogenetically normal cases. FLT3­ITD is a known bad prognostic indicator in AML patients. FLT3­ITD and FLT3­TKD mutations (choice D)​result in possible internal tandem duplications or tyrosine kinase domain point mutations. The negative effect on outcome by DNM­T3A and FLT3 mutations is not improved by having a concurrent NPM­1 mutation. An NPM­1 mutation alone is a good prognostic indicator (choice E​).

Reference
http://www.jhoonline.org/content/7/1/74


Question 2

A 12­ year­ old child who recently immigrated from Malaysia with a diagnosis of germ cell tumor and five blood transfusions presents to your emergency room in New York with fevers. Upon questioning the child's mother states that the fevers have been occurring every two days. A CBC with peripheral blood smear (depicted below) is ordered by the physician. Which of the following organisms is most consistent with this presentation?

A) P. Falciparum
B) P. Ovales
C) P. Malariae
D) P. Vivax
E) ​P. Knowlesi

Answer
D) P. Vivax


Explanation
Correct: (D) P. Vivax. Explanation: There are several clues as to the identity of this organism. Clinically, the patient is presenting with two day fevers (ternary) typical for P. Vivax as opposed to the three day fevers (quartnary) as seen in P. Malariae (Choice C). However, more importantly, the two images highlight key differences between the two organisms. This image shows an "amoeboid" amorphous trophozoite which occupies a large portion of the cytoplasm of the red blood cell. This is typically seen in P. Vivax. Other distinguishing characteristics for P. Vivax in the trophozoite stage are the tiny dots known as Schuffner's dots seen in the image. P. Falciparum shows multiple young "ring" forms of young trophozoites without evidence of mature trophozoites or schizonts. These ring forms tend to be smaller than other species and are more numerous. The key distinction for P. falciparum is the enlarged gametocyte which is often found in the peripheral blood. B: P. Ovale also exhibits Schuffner's dots, making it somewhat more difficult to distinguish from P. Vivax. However it is a more compact parasite than P. Vivax and tend to have a more round, compacter trophozoite stage. At the Schizont stage, it is fairly easy to distinguish the organisms as well. Both. P. Vivax and P. Falciparum have a stage with formation of 12­24 Schizonts, however P. Falciparum schizonts sequester in the microvasculature and capillaries and are not see in peripheral blood smear. P. Ovale tends to have much fewer schizonts, that is has at most 8­10.C: P. Malariae is a compact parasite at all stages. Its distinguishing characteristic is that the merozoites often are arranged in a rosette pattern with a clump of pigment in the center.E: P. Knowlesi is a type of malaria found in Macque monkeys found in Southeast Asia. There have been rare reports of human infection, however, little is known about this malarial species.

Reference
Wiser, Mark. Plasmodium species infecting humans. Tulane University Protozoology. 2000. Accessed on 02/24/2015. http://www.tulane.edu/~wiser/protozoology/notes/pl_sp.html

Questions taken from the Pathology ABP Exam Question Bank.

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