3.5a WBC Pathology I Flashcards by Carmela Bucoy

Lymphoid tissue consists of? (3)

Thymus
Spleen
LNs

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What are the (2) divisions of the Hematopoietic System?

Myeloid Tissue

2. Lymphoid Tissue

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Myeloid tissue includes? (2)

BM and the cells derived from it (red cells, platelets, granulocytes, monocytes)

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Myelogenous series (6)

Myeloblast
Promyelocyte
Myelocyte
Metamyelocyte
Intermediate cell
Mature cell

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How is Promyelocyte differentiated from Myeloblast?

Presence of primary granules in promyelocyte

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Of the myelogenous series:

Youngest
Scanty cytoplasm
Nucleolus

Myeloblast

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Of the myelogenous series:

First in series
Specific granules: basophil, eosinophil, neutrophil
Nucleus occupies 60% of total cell size

Myelocyte

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Of the myelogenous series:

Sunset-like
Indented nucleus

Metamyelocyte

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It is a stab/band cell

2. First to appear in PBS (counterpart of reticulocyte)

Intermediate cell

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Of the myelogenous series: has filaments separating nuclei?

Mature cell

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Refers to the decrease of WBC usually resulting from reduced numbers of NEUTROPHILS

Leukopenia

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How is leukopenia similar to anemia?

Same cause: ineffective granulopoiesis (abnormal BM cannot produce WBC)

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It refers to a clinically significant reduction in neutrophils

Agranulocytosis

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What causes ineffective/inadequate granulocytosis? (4)

Suppression of hematopietic stem cells
Suppression of committed granulocyte precursors
Ineffective maturion
Congenital conditions

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The ff describes which Ineffective/inadequate granulocytosis?

Aplastic anemia (decrease in RBC, WBC, platelets)
Granulocytopenia (accompanied by anemia, thrombocytopenia)

Suppression of hematopoietic stem cells

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What types of drugs suppress committed granulocytic precursors? (4)

Alkylating agents
Antimetabolites
Chloramphenicol
Sulfonamides

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What causes infective maturation?

Vitamin B12 deficiency –> decreased WBC

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What diseases exemplify infective maturation wherein defective precursors die in the marrow? (2)

Hint: Vit. B12 deficiency

Megaloblastic anemia

2. Myelodysplastic syndrome

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An example of an inherited defect in specific genes that impair granulocytic deifferentiation

Kostmann Syndrome - severe chronic neutropenia (manifests as infection with bacteria)

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Pathogenesis of Leukopenia (2)

Suppression of hematopoietic stem cells

2. Increased destruction/accelerated removal of neutrophils

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What causes increased destruction/accelerated removal of neutrophils? (3)

Ig-mediated injury
- Autoantibodies against WBC
- Exposure to drugs
Increased peripheral utiliation
- Massive infection (anergy)
Splenic sequestration (splenomegaly)
- Excessive destruction secondary to enlargement of the spleen

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What are the (2) main sources of WBC?

Bone Marrow

2. Lymph Nodes

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What are the (2) proliferative states?

Reactive: benign proliferation
- BM: Leukocytosis
- LN: Lymphadenitis
Neoplastic: malignant
- BM: Leukemia
- LN: Lymphoma

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(2) Reactive proliferation of WBC in BM

Leukocytosis

2. Leukemoid Reaction

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What happens in REACTIVE proliferation of WBC in BM?

Blood proliferates as a result of infection --> spills into peripheral blood

Which reactive process is being described? 1. (+) increase in number of white cells in blood 2. A common reaction to a variety of INFLAMMATORY states 3. It's focused on the infecting organism 4. It could be any of the ff: - neutrophilia - lymphocytosis - eosinophilia - monocytosis

Leukocytosis

Which leukocytosis is 1. seen in bacterial infections (pyogenic bacteria) 2. tissue necrosis --> sterile inflammation

Neutrophilia

1. Which leukocytosis is seen in chronic, viral, immunologic infections? 2. Bordatella pertusis infection

Lymphocytosis

Which leukocytosis is seen in asthma, allergy, parasitic infections?

Eosinophilia

Which leukocytosis is seen in chronic infection, collagen disorder (SLE)?

Monocytosis

Which reactive process is being described? 1. (+) high levels of WBC --> stimulation of myelogenous leukemia (reactive only, not leukemic) 2. Benign proliferation of WBC in reaction to an overwhelming infection but DOES NOT constitute leukemia 3. You do NOT see BLASTS in PBS

Leukemoid reaction

What PBS changes are seen in reactive proliferation? (2)

1. Aggravation in the primary granules found in neutrophils | 2. Reactive/Atypical lymphocytes

What morphologic changes can be seen in neutrophils during reactive proliferation in the BM? (4)

1. Toxic granules - elaboration/enlargement of ribosomes or endoplastic reticulum - coarser and darker than the normal neutrophilic granules - represent abnormal primary/azurophilic granules 2. Dohle bodies - patches of dilated ER 3. Cytoplasmic vacuoles 4. Shift to the left - younger forms of WBC (stabs, myelocytes) are seen (NEVER BLASTS! they indicate neoplastic proliferation)

Which PBS change in reactive proliferation is being described? 1. Large lymphocytes without granules (normal N:C ratio) 2. (-) Dohle bodies and toxic granules 3. Abundant and amoeboid cytoplasm --> RBCs tend to press on its borders (reaction to a virus)

Atypical lymhpocyte

What feature do atypical lymphocytes possess that distinguishes them from blasts?

N:C ratio. Blasts have scanty cytoplasm

Reactive proliferation of WBC in LNs (2)

1. Acute lymphadenitis | 2. Chronic lymphadenitis

Which process of reactive proliferation in LNs is being described? 1. A reactive change secondary to MICROBIOLOGIC AGENTS and their toxins 2. Drain foreign bodies, cell debris, bacterial products 3. Affects cervical regions (d/t microbial drainage of teeth, tonsils), and axillary and inguinal regions (d/t infection of extremities) 4. Nodes involved are PAINFUL and ENLARGED

Acute lymphadenitis

Which process of reactive proliferation in LNs is being described? 1. LNs: NOT usually painful, NON-TENDER (nodal enlargement occurs over time) 2. Related to VIRAL conditions 3. Has three patterns

Chronic lymphadenitis

What are the (3) patterns of chronic lymphadenitits?

1. Follicular hyperplasia 2. Parafollicular/Paracortical Hyperplasia 3. Sinus Histiocytosis

Which pattern of chronic lymphadenitis is being described? 1. Refers to B-cell stimulation (humoral immune response) 2. Defined by the presence of large oblong GERMINAL CENTERS (secondary follicles), surrounded by a collar of small resting naive B cells (mantle zone)

Follicular hyperplasia

What are the (2) regions of germinal centers?

1. Centroblasts: dark zone | 2. Centrocytes: light zone

The ff are examples of which patterns of chronic lymphadenitis? 1. Toxoplasmosis 2. HIV 3. RA

Follicular hyperplasia

The ff are examples of which patterns of chronic lymphadenitis? 1. Drugs 2. IM 3. Vaccines

Parafollicular hyperplasia

Which pattern of chronic lymphadenitis is being described? | 1. Refers to T-cell stimulation

Parafollicular hyperplasia

In parafollicular hyperplasia, T-cells contain activated t-cells which are 3-4 times the size of resting lymphocytes that have round nuclei, open chromatin, several prominent nucleoli, and moderate amounts of pale cytoplasm. What do you call these cells?

Immunoblasts

Which pattern of chornic lymphadenitis is being described? 1. Increase in the number and size of cells that line lymphatic sinusoids 2. Lining lymphatic endothelial cells are hypertrophied 3. Macrophages are increased in number -->expansion and distention of sinuses

Sinus histiocytosis

What cells stimulate histiocytes and macrophages?

TH1 cells

Macrophages eat upB-cells that fail to produce Ab. These are seen in germinal centers as?

Tingle bodies - they kill bacteria

What are the broad categories of neoplastic proliferative states acc to cell origin? (4)

1. Lymphoid neoplasm 2. Plasma cell dyscrasias 3. Myeloid neoplasms 4. Histiocytoses

1. All that come from myeloid stem cells | 2. Only in BM

Myelogenous leukemia

Tumors of B-cell, T-cell, NK cell origin

Lymphoid neoplasm

Sources lymphoid neoplasm (2).

1. BM: leukemia | 2. LN: lymphoma

Which category of neoplastic proliferative states is being described? 1. Predominantly in BM 2. Leukemic type of manifestations ONLY 3. Arise from hematopoietic progenitors

Myeloid neoplasm

(3) categories of Myeloid neoplasms

1. Acute Myelogenous Leukemia (AML) 2. Myelodysplastic Syndrome 3. Chronic Myeloproliferative Disorder

Which category of myeloid neoplasm is being described? | 1. immature proliferative cells accumulate in the BM

AML

Which category of myeloid neoplasm is being described? | 1. Associated with infective hematopoiesis --> peripheral blood cytopenias

Myelodysplastic syndrome

Which category of myeloid neoplasm is being described? | 1. Increased production of one or more terminally differentiated myeloid elements --> elevated peripheral blood count

Chronic myeloproliferative disorder

Which neoplastic proliferative state is being described? | 1. Uncommon proliferative lesion of macrophages and dendritic cells

Histiocytoses

A special type of immature dendritic cell that gives rise to a spectrum of neoplastic disorders referred to as the Langerhans cell histiocytoses

Langerhans cell

What are the general classifications of lymphoid neoplasms? (2)

1. Lymphoma (arises from nodal tissue) | 2. Lymphocytic Leukemia (arises from BM)

Classification of Lymphoid Tumors (5)

1. Precursor B-cell (pre-B cell): B-ALL (Acute Lymphoblastic) 2. Precursor T-cell (pre-T cell): T-ALL 3. Peripheral B cell 4. Peripheral T cell or NK cell 5. Hodgkins Lymphoma

Leukocyte Common Antigen (LCA)

CD45

Cell antigen in WBC: T-cell (4) | hint: lower numbers

CD1 CD5 CD4/8 CD3

Cell antigen in WBC: B-cell (5) | hint: higher numbers

CD10 (germinal center B) CD19, CD20 (pre B, mature B) CD23 (mature B) IgM (plasma cell)

Cell antigens in WBC: Monocyte/macrophage (2)

CD14 | CD64

Cell antigen in WBC: Stem cell (1)

CD34

Cell antigen in WBC: Hodgkin (2)

CD15 | CD30

The diagnosis of lymphoma depends on which markers? (5)

1. CD45 - LCA; differentiates carcinomas from lymphomas 2. CD15, CD30 - Hodgkin 3. CD19 - Pan-B marker, all B cells 4. CD3 - peripheral T cell marker 5. CD1,2,5,7 - precursor T cell markers

General characteristics of Lymphoid tumors (5)

1. Monoclonal population 2. Mostly B cells 3. Each type has its own clinical presentation 4. Associated with immune abnormalities 5. Recapitulation of behavior normal counterparts

Symptoms of lymphoid tumors (3)

1. Lymphadenopathy: multiple, painless, large, coalescent (otherwise, it's lymphadenitis) 2. Nonspecific symptoms: fever, malaise, weight loss 3. Extranodal involvement

Main symptom of lymphoma

Lymphadenopathy

1. The main ideologic identification of PRECURSOR tumors | 2. Tells you that the tumor is very young

(+) TdT (Terminal Deoxynucleotidyl Transferase)

The ff describes which lymphoma/leukemia? 1. Originates from thymus 2. Adolescent males 3. Rapidly enlarging symptomatic mass: mediastinal (thymic) mass 4. (+) lymphadenopathy, (+) splenomegaly 5. Aggressive

Acute Lymphoblastic Lymphoma/Leukemia (pre-T)

Peripheral B-cell Neoplasms (7)

1. Small lymphocytic lymphoma (SLL) 2. Chronic lymphocytic lymphoma (CLL) 3. Follicular lymphoma 4. Diffuse large B-cell lymphoma (DLBCL) 5. Burkitt lymphoma 6. Mantle cell lymphoma 7. Marginal Cell Lymphoma/Maltoma

Which peripheral B-cell Neoplasm: 1. Elderly, >60, male 2. Asymptomatic/nonspecific/mild 3. BM involvement 4. Can spill into blood: LN --> BM --> blood (CLL-like picture) 5. Indolent 6. Transformation to large B-cell lymphoma --> Richter syndrom 7. Transformation to prolymphocyte

Small Lymphocytic Lymphoma (SLL)

Chromosomal abnormality in SLL

Trisomy 12

Immunophenotype of B and T markers of SLL

1. B markers: CD19, 20, 23 | 2. T markers: CD5

Which (2) B-cell tumors have a T-cell marker (CD5)?

SLL | Mantle Cell Lymphoma

The ff microscopic features describe which Peripheral B-cell Neoplasm? 1. Diffuse effacement of nodal architecture 2. No more follicles 3. (+) uniform round cells with prominent nucleoli 4. (+) prolymphocytes

SLL

The ff describe which peripheral B-cell neoplasm? 1. Abnormal B cell in blood 2. Increased WBC count (decreased WBC in SLL) 3. Its chromosomal abnormality, age, sex, distribution, clinical picture is the same as SLL

Chronic Lymphocytic Lymphoma (CLL)

Diagnosis of CLL

Absolute Lymphocyte count: >4000/cumm

The most common leukemia of adults

CLL

The ff are PBS features of which peripheral B-cell neoplasm? 1. >4-5 lymphocytes/OIO (normal: 1-3) 2. 100% lymphocytes (normal: 20-40%) 3. Smudge cell

CLL

What characteristic feature is seen in the PBS of CLL?

Smudge Cell

Lab used for diagnosis of SLL

Biopsy of LN

Lab used for diagnosis of CLL

PBS

Which peripheral B-cell neoplasm is being described? 1. M=F, middle age 2. Symptoms: generalized, painless lymphadenopathy with BM involvement 3. Genetic abnormality: t(14:18) BCL-2 protooncogene 4. Characteristically devoid of apoptotic cells (because of BLC2, which antagonizes apoptosis) 5. Indolent, incurable 6. Progress to Diffuse DLBL if with c-MYC

Follicular lymphoma

Hallmark of follicular lymphoma

t(14:18)

The ff are immunophenotypes of? CD10, 19, 20 BCL-2 protein

Follicular lymphoma

Morphological characteristics describe? 1. Well-defined germinal center 2. Follicles confined to the cortex 3. Presence of inactive B collar

Normal LN

The ff are microscopic characteristics of? 1. (+) nodular aggregates throughout LN 2. Mixture of centroblasts and centrocytes

Follicular lymphoma

The ff gross features seen in the spleen describe? | 1. Pulp follicles expanded by follicular lymphoma cells (prominent nodules)

Follicular lymphoma

What is present in follicular lymphoma that is absent in a reactive follicle?

BCL-2

Rapidly enlarging symptomatic mass at a single nodal or extranodal site - symptom of? Nodal: Waldeyer Ring Extranodal: GIT, skin, bones, brain

Diffuse Large B-cell Lymphoma (DLBCL)

Cytogenetics of DLBCL (2)

1. BCL-6 Dysregulation --> undifferentiated proliferative state Has anti-p53 activity to prevent activation of DNA repair mechanism 2. t(14:18) Leads to overexpresion of BCL-2, which is anti-apoptotic

Immunophenotype of? | CD19, 20, +/- CD10

DLBCL

Microscopic features of? 1. Large cells (compared with endothelium of the blood vessel) 2. Diffuse 3. No follicles 4. Invades adipose tissue 5. Large nuclei, diffuse chromatin, prominent nucleoli

DLBCL

Grossly, what usually produces multifocal expansion of white pulp? indolent or aggressive B-cell lymphoma?

indolent

What is the histology of Burkitt's lymphoma?

Starry sky appearance: monotonous sea of round cells interspersed with macrophages

The ff are characteristics of? 1. Children and young adults 2. Prognosis: very agressive 3. Symptoms: (african/endemic) facial, pelvic. (sporadic/nonendemic) abdominal (ileocecal, peritoneum) 4. Pathogenesis: t(8,14) of c-MYC gene, EBV 5. Immunophenotype: CD10, 19, 20; BCL-6; IgM

Burkitt Lymphoma

(2) types of Burkitt Lymphoma

1. Endemic | 2. Sporadic

Which type of Burkitt lymphoma: 1. Presents as a mass involving the mandible 2. Predilection to abdominal viscera: kindeys, ovaries, adrenals

Endemic Burkitt Lymphoma

Which type of Burkitt Lymphoma? | 1. Presents as a mass involving ileocecum and peritoneum

Sporadic Burkitt Lymphoma

Which peripheral B-cell neoplasm? 1. 50-60 years old, male 2. Presents as generalized painless lymphadenopathy + extranodal spread (BM, spleen, liver, GIT [lymphomatoid polyps]) 3. Immunophenotye: -CD23 4. Genetic abnormality: t(11:14) increased expression of cyclin D1 5. Prognosis: very poor, not curable

Mantle Cell Lymphoma

Microscopic features of? 1. (LPO) lymphoid cells surround a small, atrophic germinal center --> mantle zone pattern of growth 2. (HPO) homogenous population of small lymphoid cells with irregular nuclear outlines, condensed chromatin, scant cytoplasm

Mantle Cell Lymphoma

1. Tumors of Mucosa Associated Lymphoid Tissue (thus it's aka MALToma) 2. Erogenous group of Bcell that arise within LN, spleen, extranodal tissues 3. Evidence of somatic hypermutation of memory Bcell origin 4. Good prognosis 5. Chromosomal Abnormality: t(11:18) or t(14:18)

Marginal Cell Lymphoma/Maltomas

Characteristics of? 1. Arise from chronic inflammatory disorders 2. Remain localized for prolonged periods 3. Regress if inciting agent is eradicated

Marginal Cell Lymphoma/Maltoma

Peripheral T-cell Neoplasms (5)

1. Mycosis Fungoides/Sezary Syndrome 2. Extranodal NK/T-cell lymphoma 3. Adult T-cell lymphoma/Leukemia (CD4) 4. Anaplastic Large Cell Lymphoma (CD8) 5. Large Granular T-cell Lymphocytic Leukemia

T-cell Lymphoma of the skin (2)

1. Mycosis Fungoides | 2. Sezary Syndrome

Infiltration of the skin by neoplastic CD4 T-cells

Mycosis Fungoides

Clinical stages in Mycosis Fungoides (3)

1. Inflammatory/Premycotic Phase: Flat lesion 2. Plaque Phase: Elevation of lesion 3. Tumor Phase: Mass formation (absent in Sezary Syndrome)

Histologic characteristics of? 1. Epidermis and upper dermis are infiltrated by neoplastic T-cells 2. Cerebriform appearance (d/t infolding of nuclear membrane) 3. Extracutaneous spread (most commonly to LN, BM) - characterizes late disease progression

Mycosis Fungoides

Generalized exfoliative erythroderma

Sezary Syndrome

How does Sezary Syndrome differ from Mycosis Fungoides? (2)

1. (-) Tumor | 2. (+) Associated leukemia of sezary cells with characteristic cerebriform nuclei

1. Lethal midline granuloma | 2. Midline malignant reticulosis

Extranodal NK/T-cell Lymphoma

The ff are symptoms of? 1. Destructive masses of sinuses 2. Nasopharynx 3. Involves CENTRAL portion of FACE (destructive nasopharyngeal mass)

Extranodal NK/T-cell Lymphoma

Morphology of Extranodal NK/T-cell Lymphoma

Small and large lymphocytes invading small BV --> necrosis

Extranodal NK/T-cell Lymphoma is associated with which virus?

EBV

Characteristics of? 1. Biopsy: (-) malignancy due to extensive ischemic necrosis 2. Highly aggressive: responds to radiation therapy, not chemotherapy 3. Poor prognosis with advanced disease

Extranodal NK/T-cell Lymphoma

1. CD4 Tcell proliferation 2. DIRECTLY caused by Human T-cell Leukemia Retrovirus type 1 (HTLV-1) 3. Highly aggressive, poor prognosis

Adult T-cell Lymphoma

It is the ONLY lymphoma associated with a virus. Name the virus.

Adult T-cell Lymphoma: HTLV-1

Symptoms of? 1. Skin lesions: flat, thick areas 2. Hypercalcemia 3. General Lymphadenopathy 4. Enlarged liver, spleen 5. BM with peripheral blood lymphocytosis

Adult T-cell Lymphoma

Morphology of? | 1. CLOVER LEAF/FLOWER CELLS: multilobed nuclei

Adult T-cell Lymphoma

Complications of Adult T-cell Lymphoma (1)

Demyelinating disorder of brain and spinal cord

Virus that encodes Tax protein, which enhances lymphocyte growth and survival

HTLV-1

Characteristics of Hodgkins Lymphoma (opposite is true of Non-Hodgkins Lympoma) (4)

1. Localized to a single axial group of nodes: cervical, mediastinal, para-aortic 2. Contiguous spread 3. Rarely involves Waldeyer's Ring and mesenteric nodes 4. Rare extranodal presentation

Lymphoid neoplasms derived from B-cells forming neoplastic giant cells (RS cells) that induce accumulation of other inflammatory cells

Hodgkin Lymphoma

The first human cancer to be successfully treated with radiation therapy and chemotherapy

Hodgkin Lymphoma

Characteristics of? 1. (+) RS cells 2. Polymorphic cell 3. Involves a single axial LN chain 4. Spread is contiguous and stereotyped: cannot jump from site to site, LN -> spleen -> liver -> BM -> other tissues 5. Rare extranodal presentation

Hodgkin Lymphoma

Molecular pathogenesis of Hodgkin Lymphoma

Activation of NF-KB (transcription factor) by EBV

In Hodgkin Lymphoma, this determines the course, choice of therapy, and prognosis of the disease

Ann Arbor Classification

WHO classification of Hodgkin Lymphoma (5)

1. Nodular sclerosis 2. Mixed cellularity 3. Lymphocyte-rich 4. Lymphocyte depletion 5. Lymphocyte predominance

Which WHO classification of Hodgkin Lymphoma? HISTO -Bands of collagen -Lacunar cells CLINICAL FEATURE - M=F, young adults - Common in mediastinal and cervical regions - EBV-

Nodular sclerosis

Which WHO classification of Hodgkin Lymphoma? HISTO -Many different cells, many RS CLINICAL FEATURE - M>F - EBV+ - Lymphadenopathy - Biphasic age incidence

Mixed cellularity

Which WHO classification of Hodgkin Lymphoma? HISTO -Few lymphocyte -Many RS and variants CLINICAL FEATURES - Elderly, males - HIV+ - Most EBV+

Lymphocyte depletion

Which WHO classification of Hodgkin Lymphoma? HISTO -Many lymphocytes and RS CLINICAL FEATURES - Middle age, males - Enlarged LNs - EBV+

Lymphocyte-rich

Which WHO classification of Hodgkin Lymphoma? HISTO -Few RS/LH variant (popcorn cell) -(-) CD15 and 30 CLINICAL FEATURES - Young males - EBV- - Cervical/axillary lymphadenopathy

Lymphocyte predominance

Cells that release factors that induce accumulation of reactive lymphocytes, macrophages, granulocytes

RS cells

All classifications of Hodgkin Lymphoma are affected by EBV except? (2)

1. Nodular sclerosis | 2. Lymphocytic predominance

In nodular sclerosis and lymphocytic predominance, what cells are seen instead of RS cells?

NS: Lacunar cells LP: Popcorn cells

All WHO classifications of Hodgkin Lymphoma will be CD15+ and CD30+ except?

Lymphocytic predominance

Which type of Hodgkin Lymphoma? 1. Most common form of HL 2. Characterized by the presence of LACUNAR CELLS and the DEPOSITION of COLLAGEN in bands that divide LNs into circumscribed nodules

Nodular Sclerosis

RS cells (3)

PAX5+ CD15+ CD30+

Which type of Hodgkin Lymphoma? 1. Involved LNs are diffusely effaced by a heterogenous cellular infiltrate (eosinophils, T-cells) 2. Plasma cells + benign macrophages + RS cells

Mixed cellularity

Which type of Hodgkin Lymphoma? 1. Uncommon form of classical HL: reactive lymphocytes make up the majority of the infiltrate 2. Involved LNs: diffusely effaced, vague nodularity

Lymphocyte-rich

Which type of Hodgkin Lymphoma? 1. Least common form of HL 2. Characterized by a paucity of lymphocytes and a relative abundance or RS cells or their pleomorphic variants

Lymphocyte depletion

Which type of Hodgkin Lymphoma? 1. Uncommon, non-classical variant of HL 2. Involved nodes: effaced by a nodular infiltrate of small lymphocytes + macrophages 3. Contains LH (lymphocytic and histiocytic) RS variants (popcorn cell)

Lymphocyte predominance

3.5a WBC Pathology I Flashcards

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