WBC disorders 3

Question 1

reactive lymphadenitis

Answer 1

Infections and inflammatory stimuli may cause activation of immune cells and resultant lymph node enlargements

Question 2

Follicular hyperplasia

Answer 2

activated B
cells in the germinal centers. In rheumatoid arthritis,toxoplasmosis and HIV infection.

Question 3

Paracortical hyperplasia

Answer 3

activation of the T cells. Seen with viral infections like EBV

Question 4

Sinus histiocytosis

Answer 4

distension of the lymphatic
sinusoids due to hypertrophy of the endothelial cells and macrophage infiltration. Cancer deposits causing an immune response in the lymph node

Question 5

Medullary hyperplasia

Answer 5

plasma cells being activated

Question 6

Approach to Lymphadenopathy- in children

Answer 6

Reactive lymphadenopathy is common (cervical, axillary, inguinal). Nodes are usually tender, otherwise asymptomatic. May present with a history of infection or rash. No rush to biopsy, as a rule.
oFollow-up, look for decrease in size over 2-3 months

Question 7

Approach to Lymphadenopathy - in adults

Answer 7

(Over 40 years): Reactive lymphadenopathy is less likely, and there is increased concern for malignancy (lymphoma, metastatic carcinoma).
-oFine needle aspiration cytology (FNAC) or tissue biopsy is warranted, if no obvious cause for reactive enlargement is identified.

Question 8

Leukemia tumors

Answer 8

• ‘Liquid’ tumors arising from the bone marrow. • Myeloid/ lymphoid.
• Mature/Immature
• Diagnosedonperipheralbloodsmear,bone marrow aspirate, flow cytometry.

Question 9

Lymphoma tumors

Answer 9

• ‘Solid’ tumors arising from the organ involved or lymph nodes.
• Onlylymphoid.
• Mature/ Immature
• Diagnosedonbiopsyfromtissueinvolved, immunohistochemistry

Question 10

Clinical presentation of leukemias

Answer 10

• Symptoms and signs related to bone marrow (BM) replacement→cytopenias

Question 11

Clinical presentation: lymphomas

Answer 11

• In 60% of Non-Hodgkin’s lymphomas (NHL) and almost all of Hodgkin’s
Lymphomas (HL)→nontender lymph node enlargement - NODAL.
• Other 40% of NHL are extra-nodal (GI tract, skin, brain, breast, lung…) → site-
related symptoms - EXTRANODAL.

Question 12

Plasma cell neoplasms: clinical presentation

Answer 12

Bone destruction→bone pain due to pathological fractures.

Question 13

HODGKIN LYMPHOMA

Answer 13

-These involve the nodal areas more frequently; extra-nodal involvement is rare.
-Greater involvement of single axial node groups e.g., cervical, mediastinal, para- aortic.
-Mesenteric lymph nodes and Waldeyer ring are not involved.
-Orderly and contiguous pattern of spread: node group to node group→spleen→ liver→bone marrow
-Neoplastic cells are few and interspersed between non-neoplastic cells
-Seen in young adults and elderly

Question 14

Non -Hodgkins lymphoma

Answer 14

-Extra-nodal presentation
-Multiple peripheral nodes are often involved.
-Mesenteric lymph nodes and Waldeyer ring are usually involved.
-No predictable pattern of spread, usually non-contiguous
- Entire tissue is overtaken by the neoplastic cells.
-all ages
-B Cell lymphomas

Question 15

CD Markers : all leukocytes

Answer 15

CD45

Question 16

CD Markers : Tcells

Answer 16

-CD1,CD2,CD3,CD48

Question 17

CD markers : B cells

Answer 17

CD 10, CD 19, CD 20, CD 23

Question 18

CD markers : myeloid cells

Answer 18

CD 13, CD 33, Myeloperoxidase

Question 19

CD markers : Plasma cells

Answer 19

CD 38, CD 138

Question 20

CD markers : stem cells

Answer 20

CD34

Question 21

Acute Lymphoblastic Leukemia (ALL)

Answer 21

• Neoplasms arising from the immature/ precursor B or T cells (lymphoblasts).
• Most common cancer in children.

Question 22

ALL clinical presentation

Answer 22

-abrupt onset
-bone marrow suppression : Cytopenias
-o Bone marrow hypercellularity – bone pain.
o Generalized enlargement of lymph nodes (painless).
o Extramedullary hematopoiesis - liver, spleen.
o Testicular enlargement, usually unilateral.
o CNS involvement presents as headaches, blurred vision, vomiting, nerve palsies.
o Thymic enlargement in T-ALL – compression of superior vena cava and airway

Question 23

Investigations of ALL

Answer 23

-Raised total leukocyte count, abundant lymphoblasts – scant agranular cytoplasm, nuclei are large with condensed chromatin
-PAS positive
- hyper cellular bone marrow
-Cytogenetics/ PCR: 90% of ALL are abnormal – translocations, hyperploidy, deletions, hyperdiplody and/or hypoploidy.
-Tdt marker

Question 24

ALL VS AML

Answer 24

In AML we see a proliferation of myeloblasts that have a granular cytoplasm and positive for myeloperoxidase and Sudan black; CD 13 and 33.

Question 25

The prognostic factors

Answer 25

-Age (good prognosis if 2-10 ) -WBC count (adverse prognosis if more than 100000 cells) -immunophenotype ( good prognosis: pre B cell ; adverse prognosis : Pre T cell )

Question 26

Cytogenetic good prognosis

Answer 26

-Hyperploidy, t(12;21)

Question 27

Cytogenetics adverse prognosis

Answer 27

Hypoploidy, t(9;22)

Question 28

Follicular Lymphoma (FL)

Answer 28

-Neoplasms of the mature B cells that resemble follicular cells in the germinal center of lymph nodes -middle aged individuals -Strongly associated with chromosomal translocations involving BCL2 gene. -Characteristic translocation, t(14;18)

Question 29

Clinical features of FL

Answer 29

o Painless lymphadenopathy, often generalized. o At presentation, often Stage IV disease, with BM involvement (in 85%) and frequent liver and spleen involvement. -

Question 30

Morphology of FL

Answer 30

- may show two patterns of growth - nodular, or mixed nodular & diffuse enlargement of the lymph node. -It is composed of two types of cells - small and large neoplastic lymphoid cells.

Question 31

Lab investigations of FL

Answer 31

CD19, CD20, CD10 positive

Question 32

Course and complications of FL

Answer 32

-transform to DLBCL -Most of the follicular lymphomas are indolent and incurable. -Diffuse pattern and greater numbers of large cells indicate more aggressive behavior (high grade tumors).

Question 33

Diffuse Large B Cell Lymphoma (DLBCL)

Answer 33

-Neoplasms of large mature B cells that grow as diffuse masses -Can be primary (‘de novo’), or secondary to transformation of a previous low-grade lymphoma (follicular lymphoma or CLL, but most other small B-cell lymphomas can progress to DLBCL). -Associated with chromosomal translocations involving BCL6, BCL2 and other genes.

Question 34

Clinical features of DLBCL

Answer 34

o 60% present in lymph nodes, often a single rapidly enlarging mass. About 40% present as extra- nodal mass (e.g., GI tract, skin, brain, Waldeyer ring in the oropharynx). o Liver and spleen are frequently involved with large destructive masses. o B-symptoms are common (fever, weight loss, night sweats). o Often stage I or II at diagnosis, with no findings in the bone marrow.

Question 35

Morphology of DLBCL

Answer 35

oDiffuse (non-nodular) pattern, the mass is composed of large cells (4-5 times the size of a normal small lymphocyte)

Question 36

Chronic Lymphocytic Leukemia (CLL/SLL)

Answer 36

-Neoplasms arising from small, immature B cells. Its two times more common in males. • Chronic lymphocytic leukemia (CLL) and Small lymphocytic lymphoma (SLL) differ only by the extent of involvement of peripheral blood. If the lymphocyte count is more than 5000 cells/μL, we diagnose it as CLL.

Question 37

Clinical presentation of CLL

Answer 37

• Early – incidental finding of “lymphocytosis”, in a CBC done for an unrelated reason. • Later – symptoms related to cytopenias (progressive BM replacement, +/- autoimmune hemolytic anemia or thrombocytopenia). • Enlarged lymph nodes, liver or spleen (in 50-60% cases).

Question 38

Investigations for CLL/SLL

Answer 38

-abundant mature lymphocytes -Small mature-looking lymphocytes, with characteristic “smudge” cells (due to fragility). Spherocytes may appear as immune hemolytic anemia develops. - few larger cells that are often concentrated in pale “proliferation centers”. -Flow cytometry or IHC is positive for CD 19, CD 20, CD 5, CD 23, CD 45 -Chromosomal deletion at 13q; also show overexpression of BCL2.

Question 39

Cause of death in CLL/SLL

Answer 39

• Progressive pancytopenia→infections, bleeding. • Transformation to a more aggressive neoplasm, with larger cells – mostly to a diffuse large B-cell lymphoma.

Question 40

Marginal Zone Lymphoma (MZL)

Answer 40

• Indolent lymphomas arising from small mature B lymphocytes. • Arise in either nodal tissue or most commonly in extra-nodal - mucosal sites, when they are named as MALToma (Mucosa-associated lymphoid tumor). • Extra-nodal tumors arise in chronically inflamed/ infected tissues or autoimmune diseases.