myeloproliferative neoplasms

Question 1

Myeloproliferative Neoplasms (MPN)

Definition

Answer 1

MPN: clonal myeloid conditions in which blood production is deregulated and independent of growth factors
* Caused by acquired genetic defects in myeloid stem cells
* May present with unusual thromboses, splenomegaly, constitutional symptoms
* Each has a chronic phase that may progress to an acute leukemia

Question 2

Polycythemia Vera (PCV)

general

Answer 2

Acquired MPN
60% males
Median age: 60
Median survival 15 years from dx
Arterial thrombosis major cause of mortality
Risk of transformation to myelofibrosis or CML. Rarely to AML

essentially too many RBCs

Question 3

PCV

Clinical manifestations

Answer 3

Engorged Retinal Veins
Thrombosis
Gouty arthritis
Headache
Fatigue
Blurred vision
Facial plethora- constant facial redness
Palpable splenomegaly in 75% of pts

Erythromelalgia. This is a burning pain in the hands or feet, usually accompanied by a reddish or bluish coloration of the skin. Caused by an ↑ platelet count or ↑ platelet aggregation, resulting in formation of tiny blood clots in the vessels of the extremity; responds rapidly to aspirin.

pts are often itchy after a hot shower

erythromelalgia

Question 4

PCV

Laboratory findings
Genetic testing

Answer 4

↑RBCs
↑ Hct
might be increased slightly Basophilia or eosinophilia
↓EPO low
JAK2 mutation- 95% of cases
Bone marrow biopsy- Hypercellular

Question 5

PCV

major and minor criteria

Answer 5

Question 6

PCV

Primary Tx

Answer 6

Avoid iron supplements
Phlebotomy
Decrease thrombosis risk
ASA 81mg PO daily
Hydrea (Hydroxyurea)- also for sickle cell
500-1500mg PO daily
Jakafi (Ruxolitinib)
Oral Jak 2 inhibitor for those who fail or are intolerant of Hydrea

pts with JAK2

Question 7

PCV

secondary Tx

Answer 7

Likely hypoxemia related
Fix underlying etiology
Phlebotomy for Hct >55%

pts with hypoxia, COPD, smokers, sleep apnea

Question 8

Essential Thrombocytosis or -themia (ET)

general

Answer 8

Unknown etiology
Jak2, CALR, MPL mutation common
Median age: 50-60
Female > Male

Risk of thrombosis:
Age > 60yr
WBC ≥ 11,000/mcL
History of thrombosis

Bleeding risk from platelet defects

Question 9

ET

Clin man

Answer 9

Paresthesia
Erythromelalgia -Painful burning of hands with erythema
Splenomegaly
May have concurrent leukocytosis
No erythrocytosis!
Peripheral smear with large platelets

Question 10

ET

Tx

Answer 10

ASA 81mg daily
Hydrea (Hydroxyurea) 500-1,000mg PO daily
Keep platelet < 500,00/mcL

Question 11

Lymphoma

definition

Answer 11

Aberrant proliferations of white cells in lymphatic tissue such as
Lymph nodes, spleen
Some also invade extra-nodal sites

Wide spectrum of disease ranging from indolent to very aggressive

WHO classification identifies 3 major categories of lymphoid malignancies:
Non-Hodgkin lymphoma
B-cell neoplasms
T and natural killer (NK) cell neoplasms
Hodgkin lymphoma

Question 12

lymphomas

Answer 12

Question 13

Lymphoma

Pathophysiology

Answer 13

Recurring genetic abnormalities at a variety of levels
Gross chromosomal changes
Rearrangement of specific genes
Changes in oncogenes leading to overexpression
Altered expressions/mutation of proteins

Environmental factors implicated
Infectious agents
Chemical exposures
Medical treatments

Question 14

Lymphoma

severity of disease determinants

Answer 14

The differentiation stage of a malignant lymphoma does not predict its natural history
Cell surface phenotyping aids in differential diagnosis (benign versus malignant)

Question 15

Hodgkin Lymphoma

general

Answer 15

B-cell in origin
Reed-Sternberg cells
Beware: can be seen in other conditions

Types
Classical Hodgkin Lymphoma (cHL)
Nodular sclerosis
Mixed cellularity
Lymphocyte rich/depleted
Nodular lymphocyte predominant

Question 16

Hodgkin lymphoma:

Epidemiology/Etiology

Answer 16

Bimodal incidence
20s and > 50
A 3x ↑ risk in young adults with prior history of serologically confirmed infectious **mononucleosis **

Increased incidence of HL associated with
Immunodeficiency
Personal or family history of autoimmune diseases

Question 17

Hodgkin lymphoma

clin man

Answer 17

“B” symptoms present in approx. 30% of cases:
Fever > 38°C (100.4°F)
Drenching night sweats
Weight loss (>10% of body weight)

Generalized pruritus
Single LN group and spreads to contiguous areas- Late disseminated
Pain in involved lymph nodes immediately after the ingestion of alcohol - occurs in fewer than 10% of patients but specific to cHL

Question 18

Hodgkin lymphoma

PE findings

Answer 18

Diffuse/puffy swelling rather than a discrete mass may be apparent in the supraclavicular, infraclavicular, or anterior chest wall regions
~70% cervical node involvement
12% axillary nodes
9% in the inguinal nodes

Involvement of the spleen strongly dependent on histologic subtype
Rare paraneoplastic syndromes have been described in cHL at the time of diagnosis.

Question 19

Hodgkin lymphoma:

Workup/Diagnosis

Answer 19

Diagnosis of HL is made by the evaluation of involved tissue, usually an excisional lymph node biopsy
Identification of immune markers of Hodgkin lymphoma
Reed-Sternberg cells
Laboratory testing: CBCD, CMP, LDH, uric acid
CT scans and FDG-PET imaging
Bone marrow biopsy

Question 20

Hodgkin lymphoma

Tx for early, avdanced, and relapse

Answer 20

Early stage (I-II)
Chemotherapy +/- radiation

Advanced stage (III-IV)
Chemotherapy

Relapsed disease (HL returns after prior treatment)
Conventional chemo + radiation therapy
High dose chemo and autologous hematopoietic cell transplantation (HCT) +/- radiation therapy

Question 21

hodgkin lymphoma stages

Question 23

follicular lymphoma

general

Answer 23

Indolent lymphoma derived from mutated germinal center B cells
Median age: 59 years
Histologic transformation to aggressive lymphoma occurs in 30 to 40% of patients
Usually leads to death within a few years of transformation

Question 24

follicular lymphoma

S/Sx

Answer 24

Patients are often asymptomatic
Presentation
Painless, diffuse lymphadenopathy
Marrow infiltration (40-70%)
Hepatosplenomegaly
Peripherally circulating lymphoma cells

May live for many years in good health without therapy
Most patients eventually develop progressive lymphadenopathy causing symptoms

Question 25

follicular lymphoma

Tx

Answer 25

“Watch-and-wait” approach is the standard for asymptomatic disease
Treatment does not change overall survival

Treat once symptomatic
Many regimens effective at inducing remissions
Rituximab (CD-20 directed)
Localized radiation

Question 26

Mantle cell lymphoma

general

Answer 26

Most commonly involves lymph nodes
May involve extranodal sites, including the GI tract (lymphomatous polyposis)
Male patients age >60
Widespread disease
10-15% present with a more indolent, chronic course
Splenomegaly in 40%
Bone marrow involved in majority of patients
50% present with blood involvement, sometimes overt leukemic phase

Despite high initial response rates, early relapses frequent
Median survival 3-5 years

Question 27

Burkitt Lymphoma

general

common on pance

Answer 27

Highly aggressive lymphoma with characteristic chromosomal translocations of MYC gene

Presents in three clinically distinct forms:
* Endemic
Jaw or facial bone tumor
May spread to extranodal sites, especially to the marrow and meninges
Almost all cases are EBV-positive
* Nonendemic forms (Sporadic and Immunodeficiency- associated- HIV involvement)
Abdominal mass in approximately 65% of cases, often with ascites.
Extranodal sites, such as the kidneys, gonads, breast, marrow, and CNS, may be involved.

Patients with more than 25% marrow involvement with malignant cells often are referred to as having Burkitt cell leukemia

Question 28

Burkitt lymphoma

In the absence of CNS prophylaxis

Answer 28

up to 30 percent of patients with Burkitt lymphoma/leukemia will develop leptomeningeal involvement/recurrence regardless of HIV status
Most receive intrathecal chemotherapy prophylaxis

Question 29

Burkitt Lymphoma

Tx

Answer 29

For patients with relapsed or refractory disease – possibly stem cell transplant

There is no agreed upon standard treatment for Burkitt lymphoma/leukemia in the HIV seronegative population, and limited data for HIV positive patients.