HEMATOLOGY WBC PATHOLOGY MBBS NOTE

• Infectious mononucleosis is an acute, self-limited disease of adolescents and young adults that is caused by the Epstein Barr virus
• Clinically, fever, sore throat, generalized lymphadenitis, and a lymphocytosis of activated, CD8+ T cells.

 

PATHOGENESIS

• virus initially infects oropharyngeal epithelial cells and then spreads to underlying lymphoid tissue
• mature B cells are infected-B cells that are latently infected with EBV become “activated” and proliferate releasing specific antibodies
• It exists in two forms: it either causes lysis and formation of virions, or it remains in the dormant state as an extrachromosomal episome (independent division).
• The host T cell response controls the proliferation of EBV-infected B cells and the spread of the virus. These are CD8+ T lymphocytes which are called atypical lymphocytes and are characteristic of IMN.

Peripheral blood leukocytosis; the white cell count is usually between 12,000 and 18,000 cells/µL.

Large atypical lymphocytes, 12 to 16 µm in diameter, with an oval, indented, or folded nucleus and abundant cytoplasm with a few azurophilic granules.

Atypical lymphocytes are seen accumulated in the spleen and liver thus showing HEPATOSPLENOMEGALY.

 

DIAGNOSIS

• the presence of atypical lymphocytes in the peripheral blood.
• a positive heterophile agglutination reaction (Monospot test).
• a rising titer of antibodies specific for EBV antigens.

 

COMPLICATIONS

• hepatic dysfunction, leading to liver failure
• Other complications involve the nervous system, kidneys, bone marrow, lungs, eyes, heart, and spleen
• B cell lymphoma.

 

MULTIPLE MYELOMA

B CELL MALIGNANCIES

PATHOGENESIS

• chromosomal translocations that fuse the IgH locus on chromosome 14 to oncogenes such as the cyclin D1 and cyclin D3 genes
• Factors namely NF-κB ligand (RANKL)-activate osteoclast: hypercalcemia and pathologic fractures
• production of functional antibodies often is profoundly depressed: susceptible to infections
• Renal dysfunction due to obstructive proteinaceous casts mainly consisting of BENCE JONES proteins-κ or λ light chains. This results in myeloma nephrosis.

 

HODGKIN’S LYMPHOMA

HODGKIN LYMPHOMA IS A NEOPLASM THAT ARISES FROM GERMINAL CENTER B CELLS

But the CD markers of B cells are negative

 

CLASSIFICATION BASED ON CD MARKER(IMMUNOHISTOCHEMISTRY)

 

• CLASSICAL HL{CD15(+), CD30(+), PAX5(+)}

1.Mixed cellular

2.Nodular sclerosis

3.Lymphocyte rich

4.Lymphocyte depleted

• NON CLASSICAL HL{CD15(-), CD30(-), CD20(+), Bcl6(+)}

           Nodular lymphocyte predominant

 

REED STERNBERG CELLS

Reed-Sternberg (RS) cell

• a very large cell (15 to 45 µm in diameter )
• an enormous multilobate nucleus, exceptionally prominent nucleoli
• abundant, usually slightly eosinophilic, cytoplasm.
• Particularly characteristic are cells with owl-eye appearance of two nuclei
• CD15(+), CD30(+)

CLASSICAL HODGKIN LYMPHOMA SUBTYPE	MORPHOLOGY OF RS CELL	OTHER FEATURES
NODULAR SCLEROSIS	LACUNAR CELL	Most common variety Mostly seen in young Excellent prognosis M=F
MIXED CELLULAR	MONONUCLEAR RS CELL/ CLASSICAL RS CELLS	Most common in adults >50 years Good prognosis M>F
LYMPHOCYTE RICH	MONONUCLEAR RS CELL/ CLASSICAL RS CELLS	“
LYMPHOCYTE DEPLETED	PLEOMORPHIC/ RETICULAR	Old age EBV association 90% cases Poor prognosis

 

ANN ARBOR STAGING

Each stage is further divided into A or B depending on whether they have the B symptoms, ie.

Fever

Night sweats

Weight loss.

NHL                              Multiple peripheral nodes involved usually usually	HL Usually single node involvement
Non contiguous spread spread spread	Spread via contiguity
Mesenteric nodes and Waldeyer ring are commonly involved	Both rarely involved
Extranodal involve common	Not commonly seen

 

ALL- ACUTE LYMPHOBLASTIC LEUKEMIA/LYMPHOMA

LYMPHOBLAST= Immature B or T cells

ALL can B-ALL or T-ALL, but have the same clinical picture.

 

MORPHOLOGY

• The white cell count may be greater than 100,000 cells/µL
• A few patients have no circulating blasts (aleukemic leukemia).
• Anemia almost always is present, and the platelet count usually is below 100,000/µL. Neutropenia is another common finding.
• The marrow is hypercellular and packed with lymphoblasts, which replace normal marrow elements.

 

AML-ACUTE MYELOID LEUKEMIA

• AML affects adults >50years
• Mutations causing accumulation of myeloid precursors (blasts) in the marrow.

MORPHOLOGY

• The white cell count may be greater than 100,000 cells/µL
• A few patients have no circulating blasts (aleukemic leukemia).
• Anemia almost always is present, and the platelet count usually is below 100,000/µL. Neutropenia is another common finding.
• The marrow is hypercellular and packed with lymphoblasts, which replace normal marrow elements.

 

FAB CLASSIFICATION OF ALL

FEATURES	L1	L2	L3
BLAST MORPHOLOGY	Small and equal cells Scanty cytoplasm Regular homogenous nucleus	Heterogenous cells Variable/ abundant cytoplasm Variable, heterogenous nucleus with clefts	Large homogenous cells Vacuoles in abundant cytoplasm Stippled, homogenous regular nucleus
AGE	children	adult	Adult
PROGNOSIS	Good	Intermediate	Poor
STAIN	PAS+(Per-iodic Acid Schiff)	PAS+	PAS-, SBB+(Sudan Black B)

 

AML-ACUTE MYELOID LEUKEMIA

• AML affects adults >50years
• Mutations causing accumulation of myeloid precursors (blasts) in the marrow.

MORPHOLOGY

• AML myeloid blasts or promyelocytes make up more than 20% of the bone marrow cellularity.
• Myeloblasts having three to five nucleoli, and fine azurophilic cytoplasmic granules.
• Auer rods, distinctive red-staining rodlike structures are seen in myeloblasts. They are particularly numerous in acute promyelocytic leukemia.

 

FAB CLASSIFICATION OF AML

 

SUBTYPE	NAME
	DIFFERENTIATION BASED
M0	AML with minimal differentiation
M1	AML with differentiation
M2	AML with maturation
M3	Acute promyelocytic leukemia
	LINEAGE BASED
M4	Acute myelomonocytic leukemia
M5	Acute monocytic leukemia
M6	Acute erythroblastic leukemia
M7	Acute megakaryoblastic leukemia

 

What is the diagnosis?

A 60 year old male presented with fatigue, petechiae to the Medicine OPD. The patient had a prior history of smoking and has had history of radiation exposure during work. You sent for a CBC and peripheral smear for the patient and the results are given below. What is the diagnosis?

TEST	VALUE
Hb	10g/dl
TC	52000/mm3
DC	N20L20E2M0
PLT	33000/mm3

 

ACUTE PROMYELOCYTIC LEUKEMIA/AML M3

(15;17) translocation

The chimeric gene produces a PML/RARA (retinoic acid receptor α) fusion protein that blocks myeloid differentiation at the promyelocytic stage.

This AML shows maximum occurrence of Auer rods

TREATMENT:

ATRA- All trans retinoic acid is used which causes induction of myeloid differentiation into neutrophils.

Also combination treatment with arsenic trioxide has also shown increased cure rates by 80%.

 

CML- CHRONIC MYELOID LEUKEMIA

MYELOPROLIFERATIVE NEOPLASMS-(Activated tyrosine kinases)

• CML
• POLYCYTHEMIA VERA
• ESSENTIAL THROMBOCYTHEMIA
• PRIMARY MYELOFIBROSIS

BCR-ABL fusion protein - Activates TYROSINE KINASE ENZYME -

Proliferation of myeloid cells - CML

 

CELL MORPHOLOGY AND BLOOD PICTURE

• The leukocyte count is elevated, often exceeding 100,000 cells/µL.
• The circulating cells are predominantly neutrophils, metamyelocytes, and myelocytes, and platelets are usually increased.
• The bone marrow is hypercellular
• The red pulp of the enlarged spleen resembles bone marrow because of the presence of extensive extramedullary hematopoiesis, which often leads to splenic infarct.

 

PHASES OF CML

CML initially has a slow progression such that, even without treatment, median survival is 3 years.

FEATURES	CHRONIC PHASE	ACCELERATED PHASE	BLAST CRISIS
BLAST% (MYELOBLASTS)	<10%	10-19%	>/= 20%
BASOPHIL%	0-19%	>/= 20%	___

 

LAB DIAGNOSIS

INITIAL INVESTIGATIONS

• CBC
• PERIPHERAL SMEAR
•  

CONFIRMATORY INVESTIGATIONS

• BONE MARROW BIOPSY
• CONFIRM PHILADELPHIA CHROMOSOME

1.FISH(fluorescence in situ hybridisation)

2.RT-PCR

3.KARYOTYPING

 

TREATMENT

Tyrosine kinase inhibitors

IMATINIB

BOSUTINIB

DASATINIB

NILOTINIB

Absolute treatment- Bone marrow transplant.

 

IMPORTANT PORTIONS

There are a few 2 mark topics from this region including

• BURKITT LYMPHOMA
• FOLLICULAR LYMPHOMA
• HAIRY CELL LEUKEMIA
• MYCOSIS FUNGOIDES & SEZARY SYNDROME
• WALDENSTORM’S MACROGLOBULINEMIA.

 

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