Incidental Absolute Leukocytosis Connie Shen, MS2
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1 Incidental Absolute Leukocytosis Connie Shen, MS2
2 Clinical History An otherwise healthy 73-year-old Caucasian man presents for a rou=ne physical. Review of systems is nega=ve. A CBC was obtained and reveals a leukocytosis with an absolute lymphocytosis. Peripheral blood smear review and flow cytometry were performed.
3 Peripheral Blood Smear 100x 200x
4 630x Peripheral Blood Smear
5 Peripheral Blood Smear Descrip>on At low magnifica=on, we note the presence of leukocytosis comprised of small to medium sized lymphocytes. At higher magnifica=on, the lymphocytes have very round nuclei have condensed soccer ball - like chroma=n, lack nucleoli, and have scanty cytoplasm. Smudge cells are noted.
6 Flow Cytometry
7 Ques>on #1 Which of the following sentences is true concerning the data from the flow cytometry? A. The results show polyclonal B-cell popula=on as seen by the 4:1 kappa:lambda ra=o. B. The cell popula=on of interest is dimly CD20+ C. The cell popula=on of interest are the red blood cells D. Roughly 84% of the cells are CD19 nega=ve
8 Ques>on #1 Answer and Ra>onale Correct Answer: Choice B the cell popula=on of interest is dimly 20+ The purpose of this ques=on is to reinforce how to interpret flow cytometry sca[er plots and remember the an=gens commonly expressed on the different leukocytes. In the CD19 vs CD5 plot, we no=ce that the propor=on of CD19+ B-cells is markedly skewed (85%) with respect to normal (up to 20%). This suggests that there is probably a neoplas=c prolifera=on of B- cells and, thus, choice B is correct. Choice A is incorrect as the lower lea flow cytometry graph shows a kappa:lambda ra=o of 0.07:86.12 (= ). Choice C is incorrect as red blood cells are lysed before rou=ne flow cytometry is performed. Finally for D, ~84% of cells are CD19+, so this statement is false.
9 Ques>on #2 Smudge cells appear in which of the following disease processes? A. Bordetella Pertussis B. Hairy Cell Leukemia C. Atrial Fibrilla=on D. Ehlers-Danlos Syndrome Type III
10 Ques>on #2 Answer and Ra>onale Correct Answer: Choice A Bordetella Pertussis While smudge cells are most famously associated with chronic lymphocy=c leukemia (CLL), they can also appear in other disease states in which there is a lymphocytosis, such as infec=ous mononucleosis, pertussis, and in other lymphomas/leukemias. Hairy cell leukemia characteris=cally shows hairy cell projec=ons, so choice B is incorrect. For C, atrial fibrilla=on is not related to white cells. For D, Ehlers-Danlos syndrome Type III describes a problem producing collagen, with symptoms being hypermobility and pain. Collagen is an extracellular material. One of the elements associated with smudge cell forma=on, however, is vimen=n content. Vimen=n is a intermediate filament and is found inside the cell, and low amounts of it results in more smudge cells.
11 Ques>on #3 Which of the following gene=cs confers a favorable prognosis in this malignant neoplasm? A. Dele=on 17p13.1 B. Dele=on 11q22.33 C. Trisomy 12 D. Dele=on 13q14
12 Ques>on #3 Answer and Ra>onale Correct Answer: Choice D dele=on 13q14 To answer this ques=on correctly, you must be able to correctly iden=fy the characteris=c immunophenotype of CLL in the flow cytometry sca[er plots [CD5+, CD19+, dim CD20+, CD23+, dim surface lambda light chain+]. Choice D is correct, as those with a 13q14 dele=on have a median survival of 133 months. CLL pa=ents with a normal cytogene=c status have a median survival of 111 months. For A and B answer choices, 17p13.1 and 11q22.3 dele=ons have the worst prognosis, with a median survival of 32 months and 79 months, respec=vely. Trisomy 12 is considered an intermediate prognos=c marker, making choice C incorrect.
13 CLL/SLL A chronic lymphoprolifera=ve disorder, chronic lymphocy=c leukemia (CLL) is characterized by an increased popula=on of mature monoclonal B-cells lymphocytes; small lymphocy=c lymphoma (SLL) and CLL are iden=cal diseases, with SLL presen=ng with lymphadenopathy and CLL presen=ng in the peripheral blood. The molecular pathogenesis of CLL is complex, and many steps are s=ll unknown. Most pa=ents are male, over the age of 50, and oaen asymptoma=c, but may present with fa=gue, weight loss, anorexia, generalized lymphadenopathy, and hepatosplenomegaly. CLL/SLL is diagnosed using a combina=on of morphologic and immunophenotypic evalua=on. The morphologic evalua=on can be undertaken in peripheral blood and/or lymph node specimens. Immunophenotypically, CLL/SLL is posi=ve for CD5 and CD23 and shows reduced intensity of CD20, surface light chain, and FMC-7 expression. CLL/SLL has a tendency to transform to more aggressive lymphoid neoplasms, such as diffuse large B-cell lymphoma (Richter s syndrome, ~10% of pa=ents). Pa=ents are grouped by the Rai and Binet staging systems which are based on physical exam and CBC findings. Not all pa=ents diagnosed with CLL require treatment at =me of diagnosis, and which treatment chosen depends on the stage and cytogene=c classifica=on. For localized SLL, involved-field radia=on therapy is preferred over systemic chemotherapy or watchful wai=ng, while symptoma=c or advanced stage SLL treatment is aimed towards symptom improvement and improving survival. As previous discussed, the survival varies substan=ally with a median overall survival of ~10 years.
14 Bibliography Glassy E, ed. Color Atlas of Hematology: An Illustrated Field Guide Based on Proficiency Tes=ng. Northfield, Illinois: College of American Pathologists; Nabhan C, Raca G, Wang YL. Predic=ng Prognosis in Chronic Lymphocy=c Leukemia in the Contemporary Era. JAMA Oncol. 2015;1(7):965. doi: / jamaoncol Nowakowski GS, Hoyer JD, Shanafelt TD, et al. Percentage of Smudge Cells on Rou=ne Blood Smear Predicts Survival in Chronic Lymphocy=c Leukemia. J Clin Oncol. 2009;27(11): doi: /jco Rai K, S=lgenbauer S. Clinical presenta=on, pathologic features, diagnosis, and differen=al diagnosis of chronic lymphocy=c leukemia. UpToDate. h[p:// www-uptodate-com.liboff.ohsu.edu/contents/clinical-presenta=on-pathologic-features-diagnosis-and-differen=al-diagnosis-of-chronic-lymphocy=cleukemia?source=machinelearning&search=cll&selectedtitle=4~150&sec=onrank=5&anchor=h18. Published March Accessed April 13, Rai K, S=lgenbauer S. Overview of the treatment of chronic lymphocy=c leukemia. UpToDate. h[p:// Published March Accessed April 14, Saba=ne M. Pocket Medicine. 5th ed. Philadelphia, PA: Lippinco[ Williams & Wilkins, a Wolters Kluwer; 2014.
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