About splenomegaly

1. APPROACH TO PATIENT WITH MASSIVE
SPLENOMEGALY
SARA ZEHRA
SYEDA FATIMA
NIDA ANEES

2. CASE:
A 50 year old male, known case of DM, resident of
Korangi, radiology technologist by profession
came via OPD with c/o fever (recurrent and
undocumented), night sweats, early satiety,
weight loss, bone pain and abdominal discomfort
for 3 month. No significant past medical hx, family
hx or travel hx.
On examination he’s found to be anemic,
abdominal examination revealed massively
enlarged spleen along with hepatomegaly. There
was no lymphadenopathy. The remainder of his
exam was unremarkable.

3. DIFFERENTIAL DIAGNOSIS:
(on the basis of splenomegaly)
• Chronic Myeloid Leukemia
• Myelofibrosis
• Leishmaniasis
• Malaria

4. MODES OF PRESENTATION OF MPD
CML POLYCYTHEMIA
RUBRA VERA
MYELOFIBROSIS ESSENTIAL
THROMBOCYTHEMIA
AGE: 50-60 YEARS AGE: > 40 YEARS AGE: > 50 YEARS AGE: 60 YEARS
SYMPTOMS:
VAGUE/
ASSYMPTOMATIC
SYMPTOMS:
LASSITUDE, HEADACHE,
BLACKOUT, PRURITIS
(SPECIALLY AFTER HOT
BATH), EPISTAXIS. HX OF
DVT, MI, CVA PRESENT
SYMPTOMS:
NIGHT SWEATS, FEVER, WT
LOSS, ABD DISCOMFORT,
EPISTAXIS/BLEEDING GUMS,
BONE PAIN
SYMPTOMS:
HEADACHE, ATYPICAL CHEST
PAIN, BLEEDING (NOSE,
GUMS ETC),
SIGNS:
ANEMIA, MASSIVE
SPLENOMEGALY,
HEPATOMEGALY
SIGNS:
PLETHORA, PALPABLE
SPLEEN, FEATURES OF
ARTERIAL OR VENOUS
THROMBOSIS
SIGNS:
ANEMIA, MASSIVE
SPLENOMEGALY,
HEPATOMEGALY, PETECHIAE
SIGNS:
MUSCLE WEEKNESS, VISUAL
IMPAIRMENT,
COLD/CYANOSED
PERIPHERY, SPLENOMEGALY

5. DISEASE: MUTATIONS: LABS: BONE
MARROW:
TREATMENT:
PRV JAK 2 >90% of
cases
HB > 160
HCT >48%
RED CELL MASS
>25%
Hypercelluler
Panmyelosis
Pleomorphic
grnaulocytes
Aspirin
Venesection
(~500ml every 4-
5 days)
CML Ph chromosome
BCR-ABL fusion
gene
WBC: >600
RBC: dec
PLT: N or inc
Blast cells
High LDH
Leukemic cells
Hypercellular
Imatinib
2nd gen TKI/
hydroxycarbamid
e (if no response
to imatinib)
ET JAK 2 PLTS: ≥1000
HCT: N
WBC: N or inc
Megakaryocyte
proliferation wd
hyperlobulated
nuclei. Minor inc
in fibrosis
Low dose aspirin
Hydroxycarbami-
de
MYELOFIBROSIS JAK 2 Leucoerythroblas
tic picture
Tear drop RBCs
Giant plts
High urate levels
Folate deficiency
Overt marrow
fibrosis
Excess of
megakaryocytes
Inc. reticulin
Red cell transfuse
Folic acid supl
Splenectomy
Ruxolitinib (JAK 2
inhibitor)

6. ACUTE LEUKEMIA:
ACUTE LYMPHOBLASTIC
LEUKEMIA
• Group of neoplasms composed of
immature, precursor B (85%) or T
(15%) lymphocytes (lymphoblasts).
• Most common leukemia in children.
(Down Syndrome)
• Lymphoblasts are characterized by
positive nuclear staining for
Deoxynucleotidyltransferase (TdT)
• Bone marrow biopsy shows
lymphoblasts having AGRANULAR
CYTOPLASM.
ACUTE MYELOID LEUKEMIA
• Neoplastic accumulation of
immature myeloid cells.
• Most commonly arises in older
adults (50-60 years)
• Myeloblasts are characterized by
positive cytoplasmic staining for
Myeloperoxidase (MPO).
• Bone marrow biopsy shows AUER
RODS (fused azurophilic granules in
cytoplasm of myeloblasts).
Neoplastic proliferation of blasts; define as accumulation of >20% blasts in the
bone marrow.

7. PATHOGENESIS OF MPD:
• Hyperprolifertion of neoplastic myeloid progenitors that retain the capacity for
terminal differentiation, resulting in increase in one or more formed elements of
peripheral blood.
• Neoplastic cells seed in secondary hematopoietic organs leading to
hepatosplenomegaly.
• Associated with activating mutations in tyrosine kinase, leads to overproduction
of myeloid cells.
• Four major diagnostic entities:
• BCR-ABL Fusion gene --> CML
• JAK2 Mutations --> PV (>90%), Essential Thrombocythemia and Myelofibrosis
(50%).

8. Importance of Cytogenetic Aspects of CML:
• Defining Characteristic of CML is the chromosome abnormality, the
Philadelphia (Ph) chromosome.
• Resulting from reciprocal translocation, t(9;22), generating a BCR-ABL
fusion protein with increased tyrosine kinase activity.
• BCR-ABL gene product is detected by chromosome analysis or molecular
techniques.
• The understanding of cytogenetic and molecular physiopathology of
CML has led to the use of tyrosine kinase inhibitors as treatment for this
disease. Those without Ph have a worse prognosis.

9. Investigations:
BASELINE:
• CBC
• ESR
• Peripheral blood smear
• Serum LDH, Uric acid, folate level
• Urinalysis
DIAGNOSTIC:
• Bone Marrow Aspiration and biopsy.
• Chromosome and RNA Analysis.

10. Principles and management of
various phases of CML:
• Chronic phase:
It’s is responsive to treatment.
First line therapy: Imatinib. It inhibit BCR ABL tyrosine
kinase activity and reduced uncontrolled proliferation of
white cells. With 18 months therapy complete
disappearance of ph chromosome in about 76%.
Patients are monitored by repeated BME until complete
cytogenetic response and then 3 months PCR for BCR ABL
mRNA in blood.
2nd line therapy: for those fails to response imitinib, given
second generation of tyrosine kinase inhibitor like dasatinib,
nilotinib, allogenic HSCT or classical cytotoxic drugs like
hydroxycarbamide (hydroxurea) or interferon.

11. Cont..
• Accelerated phase:
Its management is difficult. Imitinib can be given if
not given previously or hydroxycarbamide and low dose
cytarabine.
• Blast crisis: ( myeloblastic/ lymphoblastic)
Lymphoblastic proliferation better response with
treatment rather than myeloblastic proliferation.
Lymphoblastic proliferation :Treat like acute leukemia.
Induction (vincristine) consolidation ( daunorubicin)
maintaince ( prednisolone)
Myeloblastic proliferation : allogenic transplantation
have better outcome
Patient with advance disease respond to second
generation tyrosine kinase inhibitors and allogenic HSCT.

12. Bone marrow
(HSCT)transplantation:
• Indications:
• Neoplastic disorders affecting stem cell
compartments (e.g. leukemias)
• Failure of hematopoiesis e.g. aplastic anemias
• Major inherited defects in blood cell production
e.g. thalassemia, immunodeficiency diseases
• Inborn errors of metabolism with missing
enzymes or cell lines

13. Complications
• Early:
• Anemia
• Infections
• Bleeding
• Acute GVHD
• Mucositis (pain, nausea, diarrhea)
• Liver veno-occlusive disease
• Late:
• Chronic GVHD
• Infertility
• Cataracts
• Secondary malignancy

14. Counselling
• Introduce
• Greet
• Explain disease to the patient
• Answer all questions and fear of Patient and family
• Discuss the treatment plan with patient and family
members, duration, side effects
• Treatment importance and prognosis
• Life style modifications and Encourage patient
towards hope