Neoplastic Proliferations of WBC

Lymphoid Neoplasms
Precursor B and T cell Neoplasms
Acute Immatue B or T T-ALLS: Gain of function in Marrow is hypercellular and Immunostaining for TdT Factors with worse prognosis:
Lymphoblastic cells NOTCH1 packed with lymphoblasts (deoxynucleotidyl - Age<2 y/o, with translocations
Leukemia / (lymphoblasts) transferase) involving MLL gene
Lymphoma B-ALLS: loss of function in PAX5, Scant basophilic cytoplasma, - Adolescence/adult
B-ALLS E2A, EBF and nuclear larger than those B-ALLS – CD19, PAX5, CD10 - Peripheral blood blast count
- Most childhood acute - Balanced t(12;21) small lymphocytes >100,000
common leukemia involving ETV6 and T-ALLS – CD1, 2, 5, 7
cancer in T-ALLS  thymic RUNX1 Favorable prognosis:
children lymphomas (male) - 2-10 y/o
- low WBC count
- hyperdiploidy
- trisomy of chromosomes 4,7,10
- presence of t(12:21)
Peripheral B cell Neoplams (mature B cell)
Chronic CLL >5000 per Chromosal translocations are Proliferation centers with Pan B cell markers: CD19, Asymptomatic at diagnosis
Lymphocytic mm3 rare mitotically active cells CD20, CD23 and CD5 Nonspecific symptoms
Leukemia - pathognomonic
- most Median age = 60 Deletions of 13q14.3, 11q, 17p, Low levels expression of Small monoclonal Ig spike
common years old trisomy 12q smudge cells surface Ig
leukemia of 2:1 male Hypogammaglobulinemia  susceptibility to
adults in predominance miR-15a & miR 16-1 infections
the
Western gain of function in NOTCH1 Hemolytic anemia or thrombocytopenia 
Small Lymphocytic d/t autoantibodies made by non-neoplastic B
Lymphoma from postgerminal center cells
memory B cell or naïve B cell
(more aggressive) Overall survival: 4-6 years

Worse prognosis:
- deletions of 11q, 17p
- lack of somatic hypermutation
- ZAP-70 (augments signals produced
by Ig receptors)
- NOTCH1 mutation
- Can transform to diffuse large B
cells lymphoma, Richter syndrome
Follicular Lymphoma - from germinal B Chromosomal translocation 2 principal cells: CD19, CD20, CD10, surface - painless, generalized lymphadenopathy
cells involving BCL2 1. Centrocytes Ig, BCL6 indolent waxing and waning course
– Small cleaved cells median survival < 1 year
-most common form - (14;18) translocation – majority *CD5 is not expressed
of indolent NHL in o hallmark 2. Centroblast
US o IGH locus on Ch 14 – Large cells
o BCL2 locus on Ch 18
o Overexpression of BCL2
o Antagonizes apoptosis

- MLL2 gene mutations – encodes

for methyltransferases 
regulates gene expressions 
epigenetic abnormalities

Diffuse Large B Cell -60 y/o Dysregulation of BCL6  DNA Large cell size, 4-5x diameter of CD19 and CD20 Rapidly enlarging mass at nodal or
Lymphoma -male binding zinc finger transcriptional small lymphocyte CD10, BCL6 extranodal
repressor Diffuse pattern of growth Surface Igs
-most common form - Molecularly Waldeyer’s ring (oropharyngeal lymphoid
of NHL heterogenous T(14;18) mutation  Subtypes: tissue)
disease overexpression of BCL2 1. Immunodeficiency
associated large B cell
lymphoma
- in setting of severe T cell
deficiency (HIV)
2. Primary effusion lymphoma
- Malignant pleural or ascetic
effusion
Burkitt Lymphoma Fastest growing Translocations of MYC gene on High mitotic index IgM, CD19, CD20, CD10, Endemic: mass involving mandible,
human tumor Ch 8 Starry sky appearance BCL6 involvement of abdominal viscera
Categories: Increased MYC protein levels Royal blue cytoplasm with Very aggressive but responds to intensive
1. African Burkitt All endemic Burkitt Increase aerobic glycolysis clear vacuoles chemotherapy
Lymphoma lymphoma are Warburg effect
(endemic) latently infected
2. Sporadic (Non- with EBV
endemic)
3. Aggressive
lymphomas on
HIV infected
individuals

Plasma Cell Neoplasma and Related Disorders

- Neoplastic plasma cells that secrete monoclonal Ig (M component) or Ig fragment
- Called dyscrasias – accounts for 15% of deaths caused by lymphoid neoplasm
 - Excess light chains
- Free light chains concentrated in urine  Bence Jones proteins
Multiple Myeloma / Tumorous masses MIP1𝛼 upregulates RANKL Plasmablast : bizarre, Ig heavy chain on 14q2 Lytic bone lesions, hypercalcemia, renal
Plasma Cell scattered expression  activates multinucleated cell: Cyclin D1 on ch 11q13 failure, and acquired immune abnormalities
Myeloma throughout osteoclast 1. Flame cells Cyclin D3 on ch 6p21
skeletal system – Fiery red cytoplasm Proliferation dependent on IL-6
WNT pathway  potent 2. Mott Cells Poor prognosis: high serum levels of IL-6
inhibitors of osteoblast function – Multiple grape like CD 138, syndecan 1
cytoplasmic droplets CD56 Bones affected in descending frequency:
Net effect : bone resorption  – Russell bodies - Vertebral column, ribs, skull, pelvis, femur,
hypercalcemia (cytoplasm) clavicle, scapula
– Dutcher Bodies (nuclear) - Begins in medullary cavity  cancellous
bone  bony cortex
High levels of M proteins  - Punched out defects
rouleaux
Amyloidosis of AL type
Normochromic, normocytic anemia
Solitary myeloma Single mass in Extraosseus lessions – lungs,
(plasmacytoma) bone or soft tissue oronasopharynx, nasal sinuses
Inevitably progress to multiple myeloma (10-
20 years)
Smoledring Lack of symptoms Serum M protein > 3 g/dL Asymptomatic
myeloma and high plasma M 75% progress to multiple myeloma over 15
component year period
Monoclonal
Gammopathy of
Uncertain
Significance (MGUS)

-most common
plasma cell
dyscrasia
Lymphoplasmacytic Presents in 6th or MYD88  activates NF-kB Mast cell hyperplasia CD20, surface Ig Superficially resembles CLL/SLL
Lmphoma 7th decade of life At diagnosis: dissemination to
lymph node, spleen and liver Usually IgM, but can be IgG Hyperviscosity syndrome (Waldenstrom
has occurred or IgA macgroglobulinemia)
1. Visual impairment d/t venous
congestion
2. Neuro probs d/t sluggish blood flow
3. Bleeding d/t complexes
4. Cryoglobulinemia d/t precipitation
of Ig
 Complications from light chain Igs are rare,
no bone destruction

Lymphadenopathy, hepatomegaly and

splenomegaly
Mantle Cell (11;14) translocation Polyp like lesion High levels of cyclin D1 Painless lymphadenopathy (most common)
lymphoma - IgH locus on Ch 14 (lymphomatoid polyposis) CD19, CD20 Involvement of spleen and gut
- Cyclin D1 on ch 11 - Mucosal involvement of High surface Ig Poor prognosis, survival : 3-4 years
small bowel CD5+ and CD23-
Overexpression of cyclin D1 IgH lacks somatic
Upregulation of D1 Nodular appearance hypermutation, from naïve
Promote G1-S phase progression B cell
Centroblast/proliferative
center absent (unlike CLL/SLL)
Marginal Zone Extranodal 3 exceptional characteristics
Lymphoma marginal 1. Arise in tissues involved in chronic
lymphomas arising inflammatory diseases
Heterogenous group in chronically - Salivary gland in Sjogren
of B cell tumors that inflamed tissues - Thyroid in Hashimotos
arise within LN, - Stomach in H. pylori
spleens or Between reactive 2. Remain localized for prolonged period
extranodular tissues lymphoid 3. May regress if inciting agent is eradicated
hyperplasia and
full blown
lymphomaa

Hairy Cell Leukemia Moddle aged Point mutation in Fine hair like projections, best CD19 and CD20 Bone marrow, liver and spleen
white males serine/threonine kinase BRAF in phase contrast microscope CD11c, CD25, CD103, Splenomegaly, more common
Rare distinctive B 55 years old - Downstream of RAS Thread like or bleb like annexin A1 Hepatomegaly, less common
cell neoplasm 5:1 (M:F) extensions Lymphadenopathy, rare
Specific mutation in Valine to Cannot be aspirated (dry tap) pancytopenia
Glutamate substitution at 600th Splenic red pulp heavily
residue infiltrated
- Also in melanomas and Obliteration of white pulp
histiocytosis Hepatic portal triads affected
Peripheral T cell and NK cell Neoplasm
Peripheral T cell No pathognomonic Generalized lymphadenopathy, eosinophilia,
Lymphoma, pruritus, fever, and weight loss
Unspecified
Wastebasket
diagnosis
Anaplastic Large Cell ALK gene on Ch 2p23 Large anaplastic cells CD30
Lymphoma (ALK Horse-shoe shaped nuclei and
positive) voluminous cytoplasm
(hallmark cells)

Adult T cell Tax that activates NF-kB Multilobated nuclei (cloverleaf Skin lesions, generalized lymphadenopathy,
leukemia/lymphoma or flower cell) hepatosplenomegaly, peripheral blood
lymphocytosis, hypercalcemia
In adults infected by
HTLV-1
Mycosis Cerebriform appearance d/t Cutaneous leukocyte Cutaneous lesion progress through:
Fungoides/Sezary marked infolding of nuclear antigen (CLA) o Inflammatory premycotic phase
Syndrome membrane CCR$ and CCR10 o Plaque phase
o Tumor phase
Tumor of CD4+ T
cells that home to Sezary syndrome – manifest as generalized
the skin exfoliative erythroderma
Large Granular T cell variants: CD3+ Mild to moderate lymphocytosis and
Lymphocytic splenomegaly
Leukemia NK cell variants: CD3- and
CD56+ Lymphadenopathy and hepatomegaly are
absent

Neutropenia and anemia predominates

Felty syndrome: RA, splenomegaly,

neutropenia
Extranodal NK/ T Destructive nasopharyngeal mass
cell lymphoma Less common site: testis and skin
Hodgkin lymphoma
- Single axial group of nodes
- Orderly spread
- Mesenteric nodes and Waldeyer ring rarely involved
- Extranodal presentation rare
- Reed-Sternberg cells:
o Induce accumulation of reactive lymphocytes, macrophages and granulocytes
- 32 y/o
- 1st CA to be successfully treated with radiation and chemotherapy, curable in most
Nodular sclerosis Classical HL Lacunar variant RS cells Uncommonly associated with EBV
Deposition of collagen Excellent prognosis
Most common form Equal in male and
female
Mixed Cellularity Classical HL mononuclear 70% with EBV
Males, older age systemic symptoms: night sweats, weight
loss
prognosis good
Lymphocyte Rich Classical HL Reactive lymphocyte Classic immunophenotype 40% EBV
Mononuclear variants good prognosis
Lymphocyte Classical HL Paucity of lymphocytes 90% infected with EBV
Depletion Reactive abundance of RS cells
Adults, HIV or their pleomorphic variants less favorable
Least common patients, non
industrialized
countries
Lymphocyte RS with distinctive Multilobed nucleus (popcorn
Predominance B-cell cell)
immunophenotype
Uncommon, non-
classical variant
Myeloid Neoplasms

Histiocytes