Internal Medicine Board Review - DiscWrite CD Promotions

Internal Medicine Board 

Review 

Hematological 

Malignancy 

Samir Rizk, , 

MD

Myelodysplastic syndromes 

(MDS) Look for: 

• AAn older ld patient ti t with ith progressive i anemia i 

(low reticulocyte count), or cytopenia in 2 

or more cell ll li lines 

• Blast > 5% in the bone marrow 

• Cytogenic abnormality (chromosomes 

3,5,7,8 and 17) 

What is the chromosomal Deletion at 5q abnormality with the best 

prognosis? 

Treatment blood transfusion, transfusion erythropoietin and 

MBT if < 60 years

MDS-Diagnosis 

Peripheral smear 

• Pse Pseudo-Pelger-Huët 

do Pelger H ët 

– bilobed nuclei 

– excessively coarse 

clumping of chromatin 

Myelodysplasia 

Know that Pelger-Huët anomaly is an autosomal dominant disorder 

Heterozygous kids are asymptomatic 

Homozygous have skeletal abnormalities

Myelodysplasia 

• The most common cause of death is 

infection then AML and bleeding 

• Lenalidomide 

– Most effective in patients with deletion at 5q in 

reducing red cell transfusion requirement 

– Up to 65% will become transfusion 

independent 

The retail price of lenalidomide is estimated at $7 $7,000 000 per month

Myeloproliferative syndromes 

• Four types: 

– Chronic myelogenous leukemia (CML) 

– Polycythemia vera (PCV) 

– Idiopathic myelofibrosis 

– Essential thrombocythemia

Chronic Myelogenous Leukemia 

CML 

• Philadelphia chromosome,t(9;22) producing 

b brc/Abl, /Abl protein t i th that t hhas ttyrosine i kinase ki 

activity 

• PPatients ti t have h llow lleukocyte k t alkaline lk li 

phosphatase and splenomegaly* 

• LLeukostasis k t i (leucocyte counts > 300,000 mm3): • Headache 

• Focal neurologic deficits 

• Treatment leukophoresis*

A Board Question 

• A45-year-old A 45 year old man presents with one month- month 

history of low energy and fatigue. On 

examination his vitals are stable afebrile. You 

noticed enlarged spleen about 3 cm below the 

left costal margin. The rest of the exam is 

unremarkable k bl 

• Labs showed Hb 13.4; WBCs 34,400/L; platelet 

count of 510 510,000/L 000/ L and fluorescence study of 

bone marrow biopsy is significant for 

Philadelphia chromosome

Which of the following is the most 

appropriate i treatment? ? 

• A) Radiation therapy 

• B) Interferon alfa 

• C) OOral l hhydroxyurea d 

• D) Bone marrow transplant 

• E) Imatinib mesylate 

• Imatinib mesylate (Gleevec) an oral drug inhibits brc/Abl 

tyrosine kinase and eliminates the CML clones (95%)

CML – treatment 

For the Boards 

• Allogeneic bone marrow transplant within two 

years of diagnosis or – interferon is not used 

after the introduction of Gleevec 

• Busulfan and hydroxyurea play a role in 

reducing blood counts but are palliative and not 

curative 

• BMT during remission is the only proven 

curative i therapy h ffor patients i not responding di to 

Gleevec or became resistant

65-year-old male patient with known CML was 

treated with Imatinib mesylate presents with a 

mild fever and non painful or pruritic rash on his 

hands and trunk

Imatinib mesylate side effect 

• Imatinib mesylate induced maculopapular 

rash 

– Prominent over the extremities and trunk 

– Not painful or pruritic 

– Resolves with medication withdrawal 

• Imatinib mesylate may be restarted after 

resolution of the symptoms y without 

recurrence – TRUE or FALSE 

• TRUE

Polycythemia vera (PCV) 

A62 A 62-year-old ld male l with ith no medical di l hi history t 

complaining of pruritus after bathing- Has 

splenomegaly and his Hg 19 19.5 5 g/dL g/dL, O2 sat 

92% and normal erythropoietin level 

↑leukocyte alkaline phosphatase, Fe deficiency, and ↑ B12 level 

(due to increased binding protein transcobalamin I) 

Treat with ASA to all the patients –phlebotomy (HCT 70 year, h/o thrombosis, platelet > 400,000/µL) 

JAK 2 gene g 

occurs in almost 80% of PCV patients

Polycythemia vera (PCV) 

• Do not be tricked 

• On the Boards they will provide labs showing 

low serum iron saturation and serum ferritin 

concentration – what is the cause? 

• Rapid p use of endogenous g iron stores due to 

increased bone marrow erythroid activity 

– Not caused by blood loss or decreased dietary iron


• A 50-year-old woman presents with RUQ dull 

aching pain and ffullness llness and ccytopenias. topenias The 

spleen is palpable 5 cm below the left costal 

margin margin. Labs: HB 88.6 6 g/dL g/dL, leukocytes 44.2,000/L, 2 000/L 

and platelets 150,000 /L. A peripheral blood smear 

shows 4.5% myelocytes, y y and 1% blasts. A red 

blood cells appear as “teardrop”

The most likely diagnosis is: 

aa. Chronic myelogenous leukemia 

b. Agnogenic myeloid metaplasia 

c. AAcute t nonlymphocytic l h ti lleukemia k i 

d. Sideroblastic anemia 

b. Agnogenic myeloid metaplasia

Agnogenic myeloid metaplasia 

Myelofibrosis with Myeloid Metaplasia 

• Neoplastic stem cells migrate and make marrow in 

areas outside of the bone marrow 

• Huge splenomegaly (50% with hepatomegaly) 

• Teardrop RBCs* due to fibrosis of the bone 

marrow 

• JAK 2 gene occurs in 50% of myeloid metaplasia, 

with or without myelofibrosis 

– JAK2 mutation is not part of the diagnostic criteria but it 

is supportive

Agnogenic myeloid metaplasia 

Myelofibrosis with Myeloid Metaplasia 

• Transfusion therapy as needed 

• Low-dose oral thalidomide with or without 

prednisone may decrease the frequency of 

transfusion in some patients 

• NNo ttreatment t t for f asymptomatic t ti patient* ti t* 

• Splenectomy does not improve survival*

Essential Thrombocythemia 

• ET is the most common myeloproliferative 

disorder characterized by thrombosis 

[arterial and venous] and hemorrhage 

– RRemember b th that t th the platelet l t l t count t ddoes not t 

correlate with bleeding or clotting* 

• Micro Microvascular asc lar thrombi can present with: ith 

– Headache, and episodic TIA, dizziness 

– Erythromelalgia - pain and dusky extremities 

Avoid splenectomy (↑bleeding) 

HHydroxyurea d ffor both b th bl bleeding di and d clotting l tti conditions diti 

JAK 2 gene occurs in 50% of the patients

Know how to differentiate 

• Reactive 

• Essential 

thrombocytosis Thrombocythemia 

• Caused by acute 

bleeding, iron deficiency, 

chronic inflammatory 

diseases diseases, and cancer 

• No ↑ incidence of 

thrombosis, hemorrhage, 

or splenomegaly 

• Negative JAK 2 gene 

• Myeloproliferative 

disorder → increase in 

megakaryocytes and 

platelet 

• ↑ incidence of 

thrombosis, hemorrhage, 

or splenomegaly 

• Positive JAK 2 gene

• Acute: 

Types yp of leukemia 

– Acute myelogenous leukemia (AML) 

– Acute lymphocytic leukemia (ALL) 

• Chronic: 

– C Chronic myelogenous leukemia (C (CML) ) 

– Chronic lymphocytic leukemia (CLL)

AML - PPancytopenia t i 

• AAnemia- i pallor, ll and d ffatigue ti 

• Thrombocytopenia- bleeding and 

petechiae 

• Neutropenia- p sepsis p 

• Splenomegaly is uncommon * in AML

AML - staging system 

Stage Signs 

M1 Acute myeloblastic leukemia 

without maturation 

M2 Acute myeloblastic leukemia with 

maturation 

M3 Acute premyeloblastic leukemia t(15;17) DIC, Auer rods 

trans retinoic 

M4 Acute myelomonocytic leukemia t(8,21) • CNS disease 

M5 Acute monocytic leukemia Inv 16 

• Gingival 

hyperplasia 

• Leukemia cutis 

M6 Acute erythroleukemia 11 q 

M7 Acute megakaryoblastic 

leukemia

3 things You need to AML 

remember in M3 

Auer rods 

• Acute promyelocytic leukemia (M3) is 

associated with: 

1) DIC due to release of procoagulant from 

cytoplasmic y p ggranules. 

2) Auer rods are specific for AML and are 

especially prominent in the M3 

3) Treat with all-trans retinoic acid - It has 

retinoic acid receptor alfa gene

75-year-old male patient with known AML 

presents with painful plaques on both hands and 

a mild fever

Sweet Syndrome 

• Acute febrile neutrophilic dermatosis 

• Exam: 

– PPainful i f l erythematous th t plaques l 

– Granulocytic infiltration on histology 

• Seen with: 

– Leukemia (AML, AMML) 

– Lymphoproliferative diseases

Know how to differentiate 

• Sweet Syndrome • Imatinib mesylate 

• Acute febrile 

rash 

neutrophilic p 

• Prominent over the 

dermatosis 

extremities and trunk 

• Painful erythematous 

y 

• Not painful p or ppruritic 

plaques 

• CML 

• AML treated with 

trans-retinoic acid 

• Resolves eso es with t 

medication withdrawal

Treatment of AML treatment 

– Cytarabine (ara-C) and Rasburicase IM or IV 

( (recombinant bi t urate t oxidase) id ) 

– Daunorubicin (DNR) 

Look for tumor lysis syndrome (↑K+, Uric 

acid) give allopurinol before the treatment* 

• Treatment for acute promyelocytic leukemia (M3) 

iincludes l d all-trans ll t retinoic ti i acid id 

– 70% cure rate* 

Look for retinoic acid syndrome (pulmonary 

infiltrates, hypoxemia) treatment 

dexamethasone* 

The Dalmatian (Croatian) dog

Acute lymphoblastic 

y p 

leukemia (ALL)

Anterior mediastinal mass* 

iin young adult- d l for the Boards 

• Hodgkin’s disease 

• Non Hodgkin’s Hodgkin s lymphoma 

• Acute lymphoblastic leukemia 

The 5 "T's" 

• Terrible lymphadenopathy 

• Thymic tumors 

• Teratoma 

• Thyroid mass 

• Tortuous aortic aneurysm

ALL 

• ALL is the most common type of leukemia 

in children* 

• CNS involvement is common 

• The most responsive to therapy* 

• CD10 + indicates favorable prognosis

The FAB classification for ALL 

• L1 L1, L2 L2, and L3 

• L1 is the most common form of leukemia in 

children children. Small lymphoblasts 

• L2 two-thirds of adult ALL.The blasts are 

large 

In ALL Philadelphia chromosome is a poor 

prognostic p g 

factor – Unlike CML*

The FAB classification for ALL 

L3 

• Leukemic form of Burkitt lymphoma 

• MMature t BB-cell ll 

• Epstein-Barr virus associated 

• Bad prognosis

ALL- ALL treatment 

• Prednisone Prednisone, vincristine vincristine, and doxorubicin 

• Complete response rate in > 80% 

CNS chemoprophylaxis h h l i with ith methotrexate th t t 

and radiation to prevent CNS relapse


A 65-year-old man his routine labs: Hb 12.0 

g/dL g/dL, leukocytes leukocytes, 66 66,000/dL 000/dL , and platelets platelets, 

120,000 /dL. The differential cell count showed 

96% small lymphocytes. On physical 

examination examination, no palpable lymphadenopathy 

and no splenomegaly was detected. The 

treatment of choice is: 

• a. Observation 

• b. 

• cc. • d. 

Prednisone 

ABVD 

CHOP 

CLL- Observation- early y stage g 

and asymptomatic

Chronic lymphocytic leukemia 

The patients are often asymptomatic when diagnosed 

after lymphocytosis is picked up incidentally* 

CLL may present with widespread lymph node enlargement

CLL -Rai Rai Staging 

• 0 lymphocytosis only >10 10 yr 

• I adenopathy 6-7 yr 

• II splenomegaly 6-7 yr 

• III HB < 11 2-3 yr 

• IV platelets < 100 22-3 3yr yr 

The most common type of leukemia in USA 

No known association with radiation or alkylating 

agents

Treatment of CLL 

• Stage 0 – No treatment 

• Stage I and stage II- Treat if symptomatic: 

– WWeight i ht loss, l or night i ht sweating ti 

– Fever without overt infection 

• Stage III and stage IV- Treat all the 

patients 

• Chlorambucil or fludarabine + prednisone 

• If relapse give the same therapy* therapy

CLL – on the Boards 

• Look for a stable CLL patient with HB of 12 g/dL 

who developed significant drop of HB to 8 g/dL 

with increased bilirubin and LDH within few 

weeks 

• Think of Evans’ syndrome - immune reaction 

rather than progressive CLL – Do not start 

chemotherapy* 

• Ri Richter’s h ’ transformation f i - 3 -10% 10% of f patients i 

with CLL may transform into a large cell 

lymphoma → a very poor prognosis

Hairy cell leukemia 

A58-year-old male presents with 

A 58 year old male presents with 

pancytopenia and prominent splenomegaly*

Hairy cell leukemia 

A sub-type of CLL 

• Tartrate-resistant Tartrate resistant acid phosphatase 

positive-TRAP(+) 

• Immunophenotyping Immunophenotyping-CD11c CD11c is specific* 

•Dry tap* despite hypercellularity* in the 

bbone marrow bi biopsy 

2-chlorodeoxyadenosine (2-CdA) 

a complete remission in 85-90% 

a single 7 day course

Match these 

• A. Chronic lymphocytic leukemia (CLL) 

• BB. Hairy cell leukemia leukemia 

• C. Chronic myelogenous leukemia 

• D. 5q deletion AML 

• 

• 

EE. AAcute t promyelocytic l ti lleukemia k i 

• 1.Tartrate resistant acid phosphatase test 

• 2. Philadelphia chromosome 

• 3. Low leukocyte alkaline phosphatase 

• 44. BM aspirate often produces a dry tap 

• 5. Treat with Lenalidomide 

• 6. Massive splenomegaly and granulocytosis 

• 77. Massive splenomegaly and pancytopenia 

• 8. all-trans retinoic acid is the drug of choice

• Hodgkin disease 

LYMPHOMA 

• Non-Hodgkin lymphomas

Hodgkin Disease 

Di Diagnosis i 

• It is a B-cell malignancy 

•lymph y p node biopsy* p y look for Reed- 

Sternberg giant cell (“owl eye cell”) 

– 2% to 3% of the cells in an affected lymph node 

• Do not order needle biopsy* 

• Exploratory laparotomy is now not 

performed as a staging modality 

– Due to the use of systemic chemotherapy

Hodgkin Disease 

Ann Arbor Staging system- Important for management 

• Stage I One lymph-node region 

• Stage II Two or more lymph-node regions on 

the same side of the diaphragm 

• Stage III Lymph-node regions on both sides of 

the diaphragm 

• Stage IV Extranodal sites 

*A No B symptoms 

*BB B symptoms

Hodgkin Disease Disease- treatment 

• Staging based treatment 

– Stage I and II ABVD followed by radiation therapy 

• Radiation therapy only is indicated for older 

patients with stage I to II 

– Stage g III and IV ABVD alone 

• Do not forget - sperm cryopreservation 

Do not forget sperm cryopreservation 

before therapy in young males*

Non-Hodgkin Lymphomas 

Ri Risk k ffactors t 

• Immunodeficiency: 

– AIDS*, organ transplant 

• Viruses: 

– HTLV 1* (human T-cell lymphotropic virus type I) 

– Epstein – Barr virus 

• Chemotherapy and radiation* (after the 

treatment of Hodgkin’s disease)

Non-Hodgkin Non Hodgkin Lymphomas 

PROGNOSIS IN NON NON-HODGKIN HODGKIN LYMPHOMA 

Look at at: Better WORSE 

prognosis If prognosis if 

Size of cell is... small LARGE 

Histology is... nodular or 

follicular 

DIFFUSE 

EFFACEMENT

Non-Hodgkin Lymphomas 

Unexpected response 

• Low Low-grade grade NHL are not curable curable, but 

patients live for a long time even after 

relapse 

• In contrast, the intermediate and high- 

grade d llymphomas h are potentially t ti ll curable, bl 

but the length of survival is short if the 

patient ti td does not th have remission 

i i

This how it will be on the Boards 

• A 68-year-old woman presents with asymptomatic 

cervical i l llymphadenopathy. h d th Th The complete l t blood bl d 

count and lactate dehydrogenase values are 

normal. CT of the abdomen demonstrates mild 

lymphadenopathy. A lymph node biopsy 

demonstrates B-cell follicular (grade 1) small 

cleaved cell non-Hodgkin g lymphoma. y p The therapy py 

of choice is: 

• a. Observation 

• bb. Oral chlorambucil 

• d. Anti-CD20 antibody therapy 

• ee. CHOP

Treatment of follic follicular lar small 

cleaved cell non-Hodgkin lymphoma 

• The patient has stage III low-grade (small 

ffollicular) lli l ) non-Hodgkin H d ki llymphoma h with ith no 

evidence of bulky disease or symptoms 

• The treatment of choice is observation* 

•Early y chemotherapy py has not been shown 

to be beneficial


• A 62-year-old man is seen for 1.8-cm non-tender 

left anterior cervical lymph node. The biopsy 

specimen i showed h d diff diffuse llarge cell ll non-Hodgkin H d ki 

lymphoma. CT of the thorax, abdomen and pelvis 

and his labs including BMP, LFTs and LDH were 

normal. The patient was seen by oncologist and 

underwent bilateral bone biopsy which was 

normal normal. The treatment of choice of this patient is is: 

• a. Observation because there is no evidence of 

metastases 

• b. Prophylactic radiotherapy R- CHOP for high grade 

• c. ABVD 

• e. R- CHOP 

non-Hodgkin’s non Hodgkin s lymphoma

High grade large diffuse cell 

• High grade 

Treatment 

– Treated with aggressive combination 

chemotherapy 

– Have significantly higher cure rate than low 

grade but the median survival is 0.7 years 

– R - CHOP is the chemo for non-Hodgkin’s 

– R (rituximab) monoclonal antibody an anti- anti 

CD20 antibody that targets B-cell lymphoma 

cells – improves p 

cure rate 10-15%


On 06 certification and May 07 Recertification 

• Your patient underwent an upper 

endoscopy for the evaluation of dyspepsia 

unresponsive p to pproton ppump p inhibitors. 

• The biopsy done during the procedure for 

a 2.5 cm gastric g mucosal mass shows 

mucosa-associated lymphoid tissue 

lymphoma 

• Which of the following is the most 

appropriate management for this patient?


appropriate i t management t for f this thi patient? ti t? 

• A) Add H2 blocker bl k to t the th PPI and d repeat t 

the endoscopy in 6 months 

• B) Start radiation therapy 

• C) ) Treat with CHOP as in Non-Hodgkin’s g 

lymphomas 

• D) antibiotics and proton pump inhibitors 

Gastric mucosa-associated lymphoid tissue (MALT) 

lymphoma is associated with Helicobacter pylori. pylori 

These lymphomas respond well to antibiotics and PPI

Important subtypes of NHL 

• Lymphoblastic lymphomas are treated 

like ALL 

– Prednisone, , vincristine, , and doxorubicin 

– CNS chemoprophylaxis with methotrexate 

and radiation 

• Burkitt’s lymphoma is associated with 

EBV in Africa 

• Tumor lysis syndrome is a significant risk 

during the treatment of high-grade 

llymphomas h

On Nov 06 Recertification Exam 

• 34-year-old y woman with HIV and a CD4 count of 

60/mm³ presents with fever, diplopia, and 

difficulty speaking for the past 4 days 

A brain CT shows 3 low-density lesions in the left 

and right parietal cortex and in the posterior 

fossa. They are ring-enhancing with contrast 

infusion 

• The patient was treated for toxoplasmic 

encephalitis p with py pyrimethamine plus p 

sulfadiazine for 7 days. However, there was no 

significant improvement in her symptoms and no 

changes in the repeated CT


appropriate explanation to the patient patient’ss 

unresponsiveness to the treatment? 

A) The duration of treatment was not 

adequate 

B) Toxoplasma gondii is resistant to this 

regimen 

C) The signs on the CT scan needs at least a 

month th tto resolve l 

D) The patient most probably has CNS non- 

Hodgkin lymphoma

Lymphomas in HIV patients 

• HIV is associated with an increased 

incidence of NHL, Kaposi’s sarcoma, and 

Hodgkin’s Hodgkin s disease 

– Increased risk for CNS NHL in HIV patients 

• The optimal treatment of NHL in HIV is not 

clear 

• 1 15% % of f AIDS-related S deaths are due to 

NHL

Every Year Question 

• A62-year-old A 62 year old man is seen in a routine F/U 

Labs: normal CBC, ch7 and has M protein 

spike p of 1.8 b/dL and BM showed 4% 

plasma cells 

• What is your y diagnosis? g 

• Monoclonal gammopathy of undetermined 

significance g ( (MGUS) ) 

• What is the treatment? 

• No treatment for asymptomatic patient

Multiple Myeloma 

• Look for a patient with anemia, hypercalcemia 

and renal insufficiency 

• Lytic bone lesions, vertebral fracture, or back 

pain increased at night g 

• Low anion gap* 

• How high is the level of serum alkaline 

phosphatase? 

• Normal 

• Diagnosis: 

– Serum M protein > 3 g/dL 

– X ray of the skeleton* (which is better bone scan or X ray) 

– Plasma cells > 10% in the bone marrow

Multiple Myeloma 

Treatment 

• Melphalan can be used in patients planed 

to have stem-cell transplant 

TRUE or FALSE 

Melphalan and corticosteroids for nontransplant 

patients* 

• Chemotherapy py with thalidomide and 

autologous stem-cell transplant for 

patients < 65

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