Myeloproliferative Disorders Pathology Study Guide

Myeloproliferative Disorders

Myeloproliferative Disorders Pathology Video

Myeloproliferative disorders are neoplastic proliferation of myeloid cells.

Myeloproliferative disorders typically occur in late adulthood (average age is 55-years-old).

Myeloproliferative disorders are associated with:

Leukocytosis (high white blood cell count)
Hypercellular bone marrow

In myeloproliferative disorders there is an increase in all the cells of myeloid lineage.

Myeloproliferative disorders are categorized based on the dominant myeloid cell that is produced.

Complications include of myeloproliferative disorders include:

High risk of hyperuricemia and gout because of turnover of cells
Transition into acute leukemia or progression to marrow fibrosis

Myeloproliferative Disorders. Myelogram of someone with a myeloproliferative disorder. Elm'hadi C1,2, Khmamouche MR3, Tanz R3, Toreis M3, Mahtat E4, Allaoui M5, Oukabli M5, Messaoudi N6, Errihani H7, Ichou M3. Not altered. CC BY 4.0

Chronic Myeloid Leukemia (CML)

Chronic myeloid leukemia is due to neoplastic proliferation of mature myeloid cells, in particular, granulocytes and granulocyte precursors.

An increase of basophils is characteristic of chronic myeloid leukemia (CML).

Chronic myeloid leukemia is typically driven by the Philadelphia chromosome t(9;22), which results in the production of a BCR-ABL fusion protein with higher tyrosine kinase activity.

Imatinib, which inhibits tyrosine kinase activity, is the first line of treatment of chronic myeloid leukemia.

Splenomegaly is common in chronic myeloid leukemia.

Spleen enlargement indicates an accelerated phase of disease.

Acute leukemia transformation typically occurs shortly after.

Due to a mutation in a pluripotent stem cell, chronic myeloid leukemia can progress:

Acute myeloid leukemia (AML) (2/3 of cases)
Acute lymphoblastic leukemia (ALL) (1/3 of cases)

Leukocyte alkaline phosphatase (LAP) staining distinguishes chronic myeloid leukemia (CML) from a leukemoid reaction.

Leukocyte alkaline phosphatase (LAP) is negative in chronic myeloid leukemia (CML).

Leukocyte alkaline phosphatase (LAP) is positive in leukemoid reactions, such as reactive neutrophilic leukocytosis.

The granulocytes in a leukemoid reactions are what cause the leukocyte alkaline phosphatase (LAP) positivity.

Chronic Myeloid Leukemia. Peripheral blood (MGG stain): marked leukocytosis with granulocyte left shift Paulo Henrique Orlandi Mourao - Not altered. CC BY-SA 3.0
Chronic Myeloid Leukemia. Chronic myeloid leukemia in a 4 years old female. Peripheral blood (MGG stain). - Not altered. CC BY-SA 4.0
Chronic Myelogenous Leukemia. A G-banded karyotype showing 46,XX,t(9;22)(q34;q11.2). Red arrows indicate involved chromosomes 9 and 22. b Fluorescence in situ hybridization using the Vysis Extra Signal probe showing the BCR–ABL fusion signal. Red arrow indicates a red–green fusion (yellow) signal which confirms a BCR (green)/ABL (red) translocation. Acute compartment syndrome as the initial manifestation of chronic-phase chronic myeloid leukemia: a case report and review of the literature. Nagase Y, Ueda S, Matsunaga H, Yoshioka A, Okada Y, Machida T, Nakata K, Mima F, Takeda R, Hayashi D, Iio S, Okita K, Narahara H, Yasunaga Y, Inui Y, Kawata S - Journal of medical case reports (2016). Not altered. CC.
Chronic Myelogenous Leukemia. Bone marrow aspirate (May-Giemsa staining) showing marked myeloid proliferation without any differentiation block. Acute compartment syndrome as the initial manifestation of chronic-phase chronic myeloid leukemia: a case report and review of the literature. Nagase Y, Ueda S, Matsunaga H, Yoshioka A, Okada Y, Machida T, Nakata K, Mima F, Takeda R, Hayashi D, Iio S, Okita K, Narahara H, Yasunaga Y, Inui Y, Kawata S - Journal of medical case reports (2016). Not altered. CC.

Polycythemia Vera (PV)

Polycythemia vera (PV) is due to the neoplastic proliferation of mature myeloid cells, particularly red blood cells.

In polycythemia vera (PV) granulocytes and platelets are typically increased.

Polycythemia vera is related to JAK2 kinase mutation.

Many clinical symptoms of polycythemia vera (PV) are associated with viscous blood.

Symptoms of polycythemia vera (PV) include:

Blurry vision
Headache
High risk of venous thrombosis
Flushed face because of congestion (plethora)
Itching, particularly after a bath or shower (because of histamine release from mast cells)

Treatment of polycythemia vera (PV) includes:

Phlebotomy (first line)
Hydroxyurea (second line)

Without medical intervention, polycythemia vera (PV) typically results in death within two years.

Reactive polycythemia must be distinguished from polycythemia vera (PV).

In polycythemia vera (PV):

SaO₂ is normal
Erythropoietin (EPO) levels are low

In reactive polycythemia (PV):

SaO₂ is low
EPO is elevated

Reactive polycythemia is brought on by:

Lung illness
Sleep apnea
High altitude exposure
Renal disease

Reactive polycythemia with elevated erythropoietin (EPO) and normal SaO₂ levels are typically caused by ectopic renal cell carcinoma production of EPO.

Polycythemia Vera. BONE MARROW: POLYCYTHEMIA VERA: MYELOID METAPLASIA PHASE Blood smear from a 68-year-old woman with a 13-year history of polycythemia vera treated with phlebotomy, 32-P, and hydroxyurea. There was a 6-to 7-month history of decreasing hemoglobin level and platelet count. There are three red blood cell precursors present and slight to moderate anisopoikilocytosis. (Wright-Giemsa stain) The Armed Forces Institute of Pathology (AFIP) - PEIR Digital Library (Pathology image database). Image# 404905.. Not altered. Public Domain
Polycythemia Vera. Erythromelalgia is a rare symptom of PV, here present in a patient with longstanding polycythemia vera. Note reddish limbs and swelling. by Herbert L. Fred, MD and Hendrik A. van Dijk. Not altered. CC BY 2.0
Polycythemia. Histological features of chronic myeloproliferative neoplasmsA & B: Polycythemia Vera - Hypercellular bone marrow with increased numbers of erythroblasts and pleomorphic megakaryocytes (A:hematoxylin and eosin - magnification 200 x). Megakaryocytes show hyperlobated nuclei and are arranged in loose clusters (B: hematoxylin and eosin - magnification 1000 x)C & D: Essential thrombocythemia - No significant alterations of the myeloid and erythroid series. Megakaryocytes are significantly increased in number, show hyperlobated nuclei and are isolated or arranged in loose clusters (C: hematoxylin and eosin - magnification 1000 x). Reticulin fibers are present in a loose network with some intersections (D: Gomori argentic impregnation - 1000 x)Philadelphia-negative chronic myeloproliferative neoplasms. Bittencourt RI, Vassallo J, Chauffaille Mde L, Xavier SG, Pagnano KB, Nascimento AC, De Souza CA, Chiattone CS - Revista brasileira de hematologia e hemoterapia (2012). Not Altered. CC.
Polycythemia Vera. Hyperproliferative bone marrow of the patient diagnosed with JAK2V617F-positive polycythemia vera. Hypercellular bone marrow with grade 1 fibrosis and trilineage hyperplasia (100x). Pharmacobiological Approach for the Clinical Development of Ruxolitinib in Myeloproliferative Neoplasms. Eliaçık E, Işık A, Aksu S, Üner A, Büyükaşık Y, Sayınalp N, Göker H, Özcebe OI, Haznedaroğlu İC - Turkish journal of haematology : official journal of Turkish Society of Haematology (2015). Not ALtered. CC.
Polycythemia Vera. Bone marrow histomorphology of essential thrombocythemia (ET) and masked polycythemia vera (PV). (A) Bone marrow morphology of ET shows normocellular marrow with an increased number of large and mature megakaryocytes. Note the hyperlobulated megakaryocytes without significant pleomorphism (bone marrow biopsy, hematoxylin and eosin [H&E] stain, ×200). (B) Bone marrow morphology of masked PV (patient 1) shows a trilineage proliferation. Note the higher cellularity compared with that in (A) and an increased number of megakaryocytes displaying cytologic pleomorphism with mild atypia (bone marrow biopsy, H&E stain, ×200). Straightforward identification of masked polycythemia vera based on proposed revision of World Health Organization diagnostic criteria for BCR-ABL1-negative myeloproliferative neoplasms. Chu D, Cho YU, Jang S, Seo EJ, Park CJ - Annals of laboratory medicine (2015). Not altered. CC.

Essential Thrombocythemia (ET)

Essential thrombocythemia (ET) is due to the neoplastic proliferation of mature myeloid cells, in particular, platelets.

Red blood cells and granulocytes are also raised in essential thrombocythemia (ET).

Essential thrombocythemia (ET) is typically due to a JAK2 kinase mutation.

Symptoms of essential thrombocythemia (ET) are related excess abnormal platelets.

There is a high risk of bleeding and/or thrombosis in essential thrombocythemia (ET).

In rare cases essential thrombocythemia (ET) may advance to marrow fibrosis or acute leukemia.

Essential Thrombocythemia. Histopathological image representing a bone marrow aspirate in a patient with essential thrombocythemia. Hematoxylin & eosin stain. KGH. Not altered. CC.
Essential Thrombocythemia. Essential Thrombocythaemia Prof. Osaro Erhabor - Not altered. CC BY-SA 4.0

Myelofibrosis

Myelofibrosis is due to the neoplastic proliferation of mature myeloid cells, in particular, megakaryocytes.

Myelofibrosis is related to JAK2 kinase mutation in 50 percent of cases.

Platelet-derived growth factor (PDGF), which megakaryocytes overproduce, causes marrow fibrosis.

In myelofibrosis, splenomegaly occurs due to extra-medullary hematopoiesis.

Histology of myelofibrosis is characterized by:

A leukoerythroblastic smear with tear-drop red blood cells
Nucleated red blood cells
Immature granulocytes

Patients with myelofibrosis have an increased risk of infection, thrombosis, and bleeding.

Primary Myelofibrosis. An image from a peripheral blood smear showing tears, elliptocytes, schistocytes, and a giant platelet seen in primary myelofibrosis. 50x oil immersion. Michelle To, Valentin Villatoro. From MLS Collection, University of Alberta, https://doi.org/10.7939/R3CJ88201. Not altered. CC.