WBC DISORDERS

Myelodysplastic Syndromes (MDSs)

Characterized by progressive blood cytopenias despite BM hyperplasia

Defects in the erythroid, myeloid, and/or megakaryocytic maturation

Can be triggered by chemotherapy, radiation, and chemicals or viral infection

May transform to acute myeloid leukemia

Found in older adults, rarely in children and young adults

Dyserythropoiesis

• Oval macrocytes

• Hypochromic microcytes

• Dimorphic red blood cell (RBC) population

• RBC precursors with more than one nucleus

• RBC precursors with abnormal nuclear shapes

• RBC precursors with uneven cytoplasmic staining

• Fling sideroblasts

Dysmegakaryopoiesis

• Giant platelets

• Platelets with abnormal granulation

• Circulating micromegakaryocytes

• Large mononuclear megakaryocytes

• Micromegakaryoctes or micromegakaryoblasts or both

• Abnormal nuclear shapes in the megakaryocytes/megakaryoblasts

Dysmyelopoiesis

• Persistent basophilic cytoplasm

• Abnormal granulation

• Abnormal nuclear shapes

• Uneven cytoplasmic staining

RBC

WBC

Platelets

Abnormal Cellular Function (3)

RBC

• Shortened survival

• Decreased EPO response

WBC

• Decreased adhesion

• Deficient phagocytosis

• Decreased chemotaxis

• Impaired microbicidal capacity

Platelets

Bleeding

French-American-British Classification (FAB)

WHO

Classification of MDS (2)

1. Refractory anemia

2. Refractory anemia with ring sideroblasts (RARS)

3. Refractory anemia with excess blasts (RAEB)

4. Chronic myelomonocytic leukemia

5. Refractory anemia with excess blasts in transformation (RAEB-t)

MDS French-American-British Classification (FAB) (5)

International Consensus Classification

Addressed issue on authorship and deliberative process

Stemmed from the 2016/2022 WHO classification

MDS with low blasts and isolated 5q deletion (MDS-5q)

MDS with low blasts and SF3B1 mutation (MDS-SF3B1)

MDS with biallelic TP53 inactivation (MDS-biTP53)

Myelodysplastic Neoplasms with Defining Genetic Abnormalities (3)

MDS with low blasts and isolated 5q deletion (MDS-5q)

Myelodysplastic Neoplasms with Defining Genetic Abnormalities

Anemia (RBC) with dysplastic megakaryocytes

MDS with low blasts and SF3B1 mutation (MDS-SF3B1)

Myelodysplastic Neoplasms with Defining Genetic Abnormalities

Presence of >5% ring sideroblasts in the bone marrow

MDS with biallelic TP53 inactivation (MDS-biTP53)

Myelodysplastic Neoplasms with Defining Genetic Abnormalities

Deletion/mutation of both (2) copies of TP53 tumor repressor protein

Leads to poor prognosis

Myelodysplastic Neoplasm with Low Blasts

Myelodysplastic Neoplasm, Hypoplastic

Myelodysplastic Neoplasm with Increased Blasts

Myelodysplastic Neoplasms Morphologically Defined (3)

Myelodysplastic Neoplasm with Low Blasts

Myelodysplastic Neoplasms Morphologically Defined

Affects at least 1 lineage

<5% blasts in bone marrow, 2% blasts in peripheral blood

Myelodysplastic Neoplasm, Hypoplastic

Myelodysplastic Neoplasms Morphologically Defined

Characterized by hypocellular bone marrow with cytopenia and dysplasia

Myelodysplastic Neoplasm with Increased Blasts

Myelodysplastic Neoplasms Morphologically Defined

Characterized by having 5% to 19% blasts in the bone marrow and/or 2% to 19% blasts in the peripheral blood

Childhood Myelodysplastic Neoplasm with Low Blasts

Childhood Myelodysplastic Neoplasm with Increased Blasts

Childhood Myelodysplastic Neoplasms (2)

Childhood Myelodysplastic Neoplasm with Low Blasts

Childhood Myelodysplastic Neoplasms

Characterized by cytopenia, dysplasia

<5% bone marrow blasts and <2% blasts in the peripheral blood

Childhood Myelodysplastic Neoplasm with Increased Blasts

Childhood Myelodysplastic Neoplasms

5% to 19% blasts in the bone marrow and/or 2%-19% blasts in the peripheral blood

Myelodysplastic/Myeloproliferative Neoplasms

Includes myeloid neoplasms with clinical, laboratory, and morphologic features that are characteristic of both MDS and MPN, namely the presence of cytopenias and cytoses

Chronic Myelomonocytic Leukemia

MDS/MPN with Neutrophilia

MDS/MPN with SF3B1 Mutation and Thrombocytosis

MDS/MPN, Not Otherwise Specified

Myelodysplastic/Myeloproliferative Neoplasms (4)

Chronic Myelomonocytic Leukemia

Myelodysplastic/Myeloproliferative Neoplasms

High monocyte count but low blasts and promonocytes

MDS/MPN with Neutrophilia

Myelodysplastic/Myeloproliferative Neoplasms

May be confused with CML

Leukocytosis with morphologically dysplastic neutrophils and their precursors

MDS/MPN with SF3B1 Mutation and Thrombocytosis

Myelodysplastic/Myeloproliferative Neoplasms

Previously called MDS/MPN with ring sideroblasts and thrombocytosis

leukemia

When neoplastic cells involve mainly the bone marrow and blood, the disorder is known as a

lymphoma

When the disease is limited mainly to lymph nodes or organs, the disease is known as a

Lymphatic System

Consists of lymphatic vessels, lymph nodes, and other lymphatic organs

Function: Storage of lymphocytes, involved in the immune system, metabolism, absorption of fats, etc

1. Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)

2. Monoclonal B-cell Lymphocytosis (MBL)

3. T-Prolymphocytic Leukemia (T-PLL)

4. Hairy Cell Leukemia (HCL)

5. Large Granular Lymphocytic (LGL) Leukemia

Leukemias (5)

Hairy Cell Leukemia

B cell neoplasm

Commonly affect middle age population

Characterized by splenomegaly and cytopenia

Lymphadenopathy

Symptom for lymphoma

CD surface markers

Cytogenetics

DNA analysis/PCR

Diagnosis for lymphoma (3)

Revised European-American Lymphoma Classification (REAL Classification)

World Health Organization (WHO) Classification of Mature Lymphoid Neoplasms

Lymphoma Classification (2)

Precursor B-cell neoplasm

Mature B-cell neoplasm

Precursor T-cell neoplasm

Mature T cell and NK cell neoplasms

Hodgkin’s lymphoma

REAL Classification (5)

Hodgkin’s Lymphoma

30% of cases

Persistent defect in the cellular immunity with abnormalities in T lymphocytes and IL-2 production

Contains Reed-Sternberg cells with giant lymphocytes with more than 1 nucleus

Non-Hodgkin’s Lymphoma

Group of neoplastic disorders and include all lymphomas except Hodgkin’s disease

Reed-Sternberg Cells

Large, multinucleated cells with prominent large nucleoli (usually of B cell lineage)

Identifying characteristic of HL

Popcorn cells

A variant of RS cells

Owl-eyed appearance

RS cell appearance

Non-Hodgkin’s Lymphoma

Involve mostly B lymphocytes

Malignant proliferation of lymphoid cells without Reed-Sternberg cells

WHO/REAL Classification System

Classification of NHL

Indolent

Aggressive

Highly aggressive

WHO/REAL Classification System (3)

Indolent

(35-40% of NHL) – causing little or no pain; e.g. follicular lymphoma, small lymphocytic lymphoma

Aggressive

(50% of NHL) – poor prognosis; e.g. diffuse large B-cell lymphoma

Highly aggressive

(5% of NHL) – poorer prognosis; e.g. Burkitt and cutaneous T cell lymphoma

Adult T-cell Leukemia/Lymphoma

Associated with retroviral infection by the human T-lymphotropic virus type I (HTLV-1)

Acquired through transplacental transmission, breastfeeding, blood transfusion, or sex

Adult T-cell Leukemia/Lymphoma

Leads to osteolytic lesions, hypercalcemia, and profound immunosuppression

Characterized by presence of “flower cells”

Burkitt’s Lymphoma

Highly aggressive lymphoma of mature B cells

Strongly related to Epstein-Barr virus (EBV) infection

Occurs in children and usually affects the jaw bones

Burkitt’s Lymphoma

Characterized by neoplastic cells that are medium sized with strongly basophilic vacuolated cytoplasm

The vacuoles contain lipid and stain positively with Oil Red O

Follicular Lymphoma

Lymphoma that affects germinal B cells

Spleen is enlarged

Causes fever, weight loss, and night sweats

Follicular Lymphoma

Higher incidence in women

With a cutaneous form

Nucleus with cleft

Mantle Cell Lymphoma

Approximately 6% of NHL cases

Characterized by varied cells in the peripheral blood

Causes extensive lymphadenopathy with common extranodal disease, especially in the GI tract

Diffuse Large B-cell Lymphoma

Characterized by diffuse tissue infiltration by large B-lineage cells

Causes rapidly expanding painless lymphadenopathy in one or more sites with extranodal involvement in the GI tract, testis, or bone

Marginal Zone Lymphoma

Indolent B-cell lymphoma

Causes chronic antigen stimulation in the setting of either infection or autoimmunity

Extranodal marginal zone lymphoma of mucosa associated lymphoid tissue (MALT)

Splenic marginal zone lymphoma (SMZL)

Nodal marginal zone lymphoma (NMZL)

Marginal Zone Lymphoma (3 types)

Cutaneous T Cell Lymphoma

Most common type: Mycosis Fungoides/Sezary Syndrome

Associated with lymphocytosis of Sezary cells

Sezary Cells

T cells with a cerebriform nucleus with a distinctive folded, groove-like chromatin pattern

Sezary syndrome

Variant of mycosis fungoides seen in the leukemic stage of MF

Presents as a disseminated disease with widespread skin involvement and circulating lymphoma cells

Mycosis Fungoides/Sezary Syndrome

Caused by chronic antigenic stimulation as a result of different exposures to:

Bacterial infections

Smoking

Medications

Chronic sun exposure

Viral infections

Chemical exposition

Anaplastic Large Cell Lymphoma

T-cell disorder associated with large pleomorphic cells

Subclassified based on the presence of anaplastic lymphoma kinase protein

POS (+)

Anaplastic Large Cell Lymphoma

10-30% of childhood lymphomas

NEG (-)

Anaplastic Large Cell Lymphoma

More common in older patients

Peripheral T-Cell Lymphoma, Not Otherwise Specified (PTCL-NOS)

For disorders that do not fit any criteriaor subtype of anaplastic large cell lymphoma.

Monoclonal Gammopathy of Undetermined Significance (MGUS)

Multiple Myeloma

Plasmacytoma

Waldenstrom Macroglobulinemia

Plasma Cell Neoplasms (4)

Monoclonal Gammopathy of Undetermined Significance (MGUS)

Benign monoclonal proliferation of plasma cells in the bone marrow

Precursor multiple myeloma

Multiple Myeloma

Excessive secretion of IgG or IgAwithout significant symptoms.

Plasmacytoma

Localized form of PCN in bone without monoclonal protein in serum or urine

Waldenstrom Macroglobulinemia

Excessive secretion of IgM