WBC Disorders 4

Question 1

Burkitt Lymphoma (BL)

Answer 1

• An aggressive, extra-nodal, mature B-cell neoplasm, which resemble germinal center B-cells.
• These are variably associated with Epstein-Barr virus (EBV) infection.

Question 2

BL etiology

Answer 2

oAssociated with translocations on the C-MYC gene on chromosome 8.
oTranslocations increase transcription of MYC causing overexpression and IgH on Chromosome 14.
o Most commonly t(8;14) is seen.

Question 3

African (endemic) BL

Answer 3

Children and young adults are affected; most common sites are jaws
and facial bones but may spread to kidneys, ovaries and adrenals

Question 4

Sporadic (non-endemic) BL

Answer 4

Children and young adults are affected; most common in gastrointestinal tract and peritoneum. Clinically present as abdominal pain, bowel obstruction or gastrointestinal bleeding. Swellings may be palpable on examination.

Question 5

HIV associated BL

Answer 5

No specific age group is more at risk. Most common sites would be the CNS and the gastrointestinal tract. The present with symptoms of the site involved in addition to that of immunodeficiency.

Question 6

Morphology of BL

Answer 6

Biopsy from the tissue shows diffuse infiltrates of monotonous medium-sized B-cells, with very high mitotic rate and abundant apoptosis. Many macrophages infiltrate the tissue to ingest the debris. This leads to areas of clearing or empty spaces around these macrophages representing the ‘stars’ in a ‘sky’ of the neoplastic cells; also known as “starry sky” pattern

Question 7

Diagnosis of BL

Answer 7

CD 19, CD 20, CD 10, C-MYC, Surface IgM

Question 8

Hairy Cell Leukemia (HCL)

Answer 8

-A rare, indolent mature B-cell neoplasm arising in the bone marrow.
• The neoplastic cells have fine hair-like cytoplasmic projections.
• Median age of presentation is 55 years, it has a high preponderance in males; 5:1 is the ratio of males affected to females.

Question 9

HCL etiology

Answer 9

oStrongly associated with BRAF mutations.
oAffects the stem cells in bone marrow leading to proliferation of tumor cells with hair-like projections with the ability to cause fibrosis in the marrow. The fibrosis leads to lack of space in the marrow.

Question 10

HCL clinical features

Answer 10

-pancytopenia
-splenomegaly

Question 11

Diagnosis of HCL

Answer 11

BMA:dry tap due to reticulin fibers /hairy cells make fibrogenic GFs
BMB:fried egg appearance/small lymphocytes enmeshed in reticulin fibers/bone will be hypo cellular
PBS :small lymphocytes with bleb like cytoplasmic extensions /TRAP stain

Question 12

Flow cytometry of HCL

Answer 12

CD 19,CD 20, CD 25 are positive. Specific markers for HCL are CD 11c, CD 103 and Annexin A1.

Question 13

T/NKC lymphomas

Answer 13

• These are a heterogenous group of neoplasms that originate from mature T- cells or Natural killer-cells.

Question 14

Examples of T/NKC lymphomas

Answer 14

o Mycosis fungoides (Sézary syndrome) – are the cutaneous T cell lymphomas o Anaplastic large cell lymphoma – composed of very large bizarre cells.
o Adult T cell leukemia/lymphoma (HTLV-1 infection related) – Only RNA virus-induced cancer. They have a long latent period from infection to cancer. Present with skin lesions, lymphadenopathy and hepatosplenomegaly.
o Peripheral T cell lymphoma – most common one of this list, have non-specific features

Question 15

Plasma cell neoplasms

Answer 15

• These are a group of neoplasms that originate from B-cells with plasma cell differentiation that secrete monoclonal immunoglobulins (Ig) or fragments of immunoglobulins.
• These tumors secrete monoclonal immunoglobulins in the blood named as M- proteins.

Question 16

Classification of plasma cell neoplasms

Answer 16

Multiple Myeloma (Plasma cell myeloma) – most common and deadliest; symptomatic
patients and have a high M-protein level.
o Monoclonal Gammopathy of Undetermined Significance (MGUS) – asymptomatic patients with a moderately elevated M-protein level.
o Primary or immunocyte-associated amyloidosis – neoplastic plasma cells secreting light chain proteins (λ-type) that get deposited.
o Waldenström macroglobulinemia – high levels of IgM with symptoms of hyper- viscosity of the blood.

Question 17

Multiple Myeloma- general features

Answer 17

-males / 70 years old
-The M-protein produced by myeloma cells is IgG (60%), IgA (20%) and κ or λ light chains .
• The light chains are smaller and hence excreted in urine and are now as Bence Jones proteins.

Question 18

Pathogenesis of multiple myeloma

Answer 18

• There is dysregulation of D-cyclins leading to cellular proliferation.
• Myeloma cells upregulate RANKL (receptor activator of NF-κB ligand) in marrow cells. This activates osteoclasts and causes increased bone resorption (lytic bone lesions) and hypercalcemia.
• Increased production of abnormal cells and immunoglobulins leaves no raw material for production of normal B-cells leading to increased incidence of bacterial infections.
• Interleukin-6 produced by the normal fibroblasts and macrophages in the bone marrow is also upregulated which supports proliferation of myeloma cells. IL-6 also causes elevated fibrinogen and causes rouleaux formation of the red blood cells.
• Excretion of Bence Jones proteins in urine also leads to deposition of these proteins in the glomerulus and formation of proteinaceous casts in the convoluted tubules causing renal damage.
• Renal damage may also cause reduced erythropoietin production leading to anemia.
• Hypercalcemia leads to dehydration, renal stone formation and bacterial pyelonephritis.

Question 19

Clinical presentation of myeloid myeloma

Answer 19

-bone pains and pathological fractures
—hypercalcemia causes confusion ,weakness and lethargy ,dehydration ,renal stone formation and bacterial pyelonephritis
-reccurent bacterial infections
-renal failure

Question 20

Investigations of myeloid myeloma

Answer 20

• Complete blood count: Normocytic normochromic anemia, rouleaux formation and neutropenia.
• Bone marrow: Increased number of plasma cells more than 30% of the cells. The abnormal plasma cells have prominent nucleoli and cytoplasmic inclusions.
• Serum protein electrophoresis: Shows a sharp protein band (M-band) composed mainly of IgG.
• CRAB Criteria: Elevated serum Calcium; Renal insufficiency (elevated creatinine); Anemia and punched-out Bone lesions on imaging.
• Urinalysis: Bence Jones proteinuria and proteinaceous casts.

Question 21

Hodgkin Lymphoma (HL)

Answer 21

• These are a group of neoplasms that arise from the germinal center B- cells and are characterized by the presence of a giant tumor cell known as Reed Sternberg cell.
• Usually arise in a single lymph node or a group.
• RS cells induce accumulation of reactive lymphocytes, macrophages
and granulocytes, which make up 90% of the tumor mass.
-divided into two broad classes Classical or Variant HL

Question 22

Clinical presentation of Hodgkin lymphomas

Answer 22

• Painless and rubbery enlargement of one or more lymph nodes.
• Pain is usually seen in the involved nodes after drinking alcohol.
• Systemic B symptoms (fever, night sweats, weight loss) may be seen in some
cases.
• Cutaneous anergy leading to generalized itching or pruritis.
• Neoplastic cells are large with multiple or single nuclei with multiple lobes, large
nucleoli or an ‘owl-eye’ appearance

Question 23

Nodular Sclerosis-clinical features

Answer 23

o It is the commonest subtype of HL.
o Affects adolescents or young adults, incidence is equal in males and females.
o Mediastinal lymph nodes are more commonly involved.
o These have an excellent prognosis

Question 24

Nodular Sclerosis - morphology

Answer 24

o Large nodules, that are partly surrounded by thick fibrous collagen bands.
o Presence of a type of Reed Sternberg cell called the Lacunar RS cells

Question 25

Mixed cellularity - clinical features

Answer 25

o Most common HL in patients over 50
years of age.
o These show a bimodal distribution in
young adults and elderly.
o They have a male preponderance.
o These are frequently associated with
infection with EBV (70% of cases). o They usually have abdominal
involvement and have advanced
symptoms at the time of diagnosis.
o B symptoms are very frequently seen. o They have a very good prognosis

Question 26

Mixed cellularity - morphology

Answer 26

o Diffuse nodal replacement is seen.
o Classical RS cells seen in a background
of T cells, plasma cells, eosinophils and macrophages

Question 27

Lymphocyte rich clinical features and morphology

Answer 27

Clinical features:
o This subtype affects the elderly.
o They have a male preponderance.
o These are associated with infection with EBV (40% of cases). o They have a good to excellent prognosis.
• Morphology:
o Classical RS cells seen in a background rich in T cells.

Question 28

Lymphocyte depleted - clinical features and morphology

Answer 28

• Clinical features:
o These are mostly associated with infection with EBV (90% of cases).
o Also commonly seen in patients with HIV infection.
o They have an advanced stage at diagnosis and an unfavorable prognosis.
• Morphology:
o Classical RS cells seen in a background with scant T cells and fibrosis.

Question 29

Variant HL : lymphocyte dominant - clinical features

Answer 29

o Seen in young males, less than 35 years of age.
o Usually present with cervical and axillary lymphadenopathy.
o These have an indolent behavior and excellent prognosis.
o No associations with EBV infection.

Question 30

Lymphocyte predominant- morphology

Answer 30

o Large nodules, but do not have fibrous or collagen bands.
o Presence of a Lymphohistiocytic variant RS cell that have a delicate multilobed puffy nucleus also known as a ‘popcorn cell’