Benign Lymphocyte Disorders

Question 1

How do you identify a NK cell?

Answer 1

Large granular lymphocyte

-> only lymphocyte which will have granules to kill target cell

Question 2

How is lymphocytosis (not leukocytosis) defined in adults and infants / young children?

Answer 2

Adults - >4,000 / microliter

Infants and young children - >9,000 / microliter

Question 3

How is lymphopenia defined and what is relative lymphocytosis?

Answer 3

Lymphopenia - <1,500 / microliter

Relative lymphocytosis - absolute lymphocyte count is normal / near normal despite low WBC count -> makes up a relatively larger percentage

Question 4

How is leukocytosis vs leukopenia defined?

Answer 4

Leukopenia - <5k / ul

Leukocytosis - >10k / ul

Question 5

A patient has lymphadenopathy AND lymphocytosis. What findings suggest the cause is more likely malignant than benign?

Answer 5

> 5 cm lymph node. (very large, anything over 1 cm is abnormal)

SEVERE anemia or thrombocytopenia (viral may be mild)

Older patient or constitutional symptoms

Question 6

What are the benign acute causes of lymphocytosis / lymphadenopathy (L/L)?

Answer 6

Bordetella Pertussis (think of the popcorn spilling in sketchy)

Infectious mononucleosis (reactive lymphocytosis in infectious process)

Infectious Hepatitis

Question 7

What are the benign chronic causes of lymphocytosis / lymphadenopathy (L/L)?

Answer 7

Brucellosis
Tuberculosis
Toxoplasmosis
Secondary and congenital syphilis

Question 8

What are the malignant disorders which are associated with L/L?

Answer 8

1. Chronic Lymphoid Leukemias
2. ALL
3. Leukemic phase of lymphomas

Question 9

What are the peripheral blood smear features of infectious mononucleosis?

Answer 9

Reactive lymphocytes with atypical macrophage-like morphology (can look like blasts)

Red cell hugging - cytoplasm of CD8 reactive T cells will hug RBCs

Question 10

What establishes diagnosis of IM in a patient? How can you generally tell if an increase in antibodies is benign or malignant?

Answer 10

Heterophile IgM antibody

Can tell by running flow cytometry for B cell light chain. If both light chain types are present equally, it’s benign (polyclonal). If one is greatly favored, it’s malignant (monoclonal).

Question 11

What usually causes IM, who gets it, and what are the clinical symptoms?

Answer 11

IM usually caused by EBV, less commonly CMV. Virus infects B cells, and T cells react

Affects young people (kissing disease)

Constitutional symptoms + stiff neck

• Splenomegaly - T cell hyperplasia in PALS
• Lymphadenopathy - often generalized, usually in neck (where infection started)

Question 12

What are the atypical lymphocytes of IM called?

Answer 12

Downey cells

Question 13

What is the risk of treating IM as a bacterial infection and what is the general care we advise?

Answer 13

If patient is given ampicillin, they will develop a rash

Only give steroids in very severe symptoms, otherwise just supportive

Question 14

What are the complications of IM?

Answer 14

Splenic rupture

AIHA - due to cold agglutinins

Question 15

What is definition of localized vs generalized lymphadenopathy?

Answer 15

Localized - <3 contiguous lymph node affected

Generalized - >=3 noncontiguous lymph nodes affected

Question 16

What are the general causes of local lymphadenopathy?

Answer 16

Local infection - i.e. pyogenic infection, cat scratch, TB

Lymphomas - HL and NHL

Metastatic carcinomas

Question 17

What are the general causes of generalized lymphadenopathy?

Answer 17

Infections

Non-infectious inflammatory processes (sarcoidosis, SLE, RA)

Malignant processes which have spread more

Miscellanous (drug reactions, hyperthyroidism, sinus histiocytosis with massive lymphadenopathy)

Question 18

What are the superficial vs axial lymph nodes?

Answer 18

Superficial - accessible by physical exam

Axial - located in chest, abdomen, and pelvis, better seen by imaging. I.e. hilar nodes, para-aortic nodes.

Question 19

How do you know something is abdominal lymphadeopathy on CT and not just a blood vessel or a loop of bowel?

Answer 19

You give them both oral and IV contrast with their CT

Question 20

What features of lymphadenopathy lead you to believe its more likely a benign than a malignant process?

Answer 20

Rapid onset (days) - except for very aggressive lymphomas

Associated with pain / tenderness (lymphadenitis draining an area of infection)

Soft consistency

Question 21

What would a firm vs a woody / hard lymph node give you suspicion for?

Answer 21

Firm - Non-Hodgkin’s lymphoma

Woody hard - metastatic carcinoma

Question 22

What diagnostic workup should be done with isolated lymphadenopathy?

Answer 22

CBC with differential
Serology and cultures (for viruses and bacteria)
Flow cytometry if lymphocytes are increased

Lymph node biopsy as a last resort

Question 23

What are the four types of lymph node hyperplasia which can be detected by biopsy?

Answer 23

Follicular - stimulation of B cells

Paracortical - T cell hyperplasia

Sinus - expansion of sinus histiocytes

Angiofollicular hyperplasia - “onion skinning appearance”

Question 24

What are the causes of follicular and paracortical hyperplasia of LN?

Answer 24

Follicular - bacterial and viral infections, autoimmune diseases like RA (which overproduce Abs)

Paracortical - T cell processes, i.e. drug reaction and infectious mononucleosis

Question 25

What are the causes of sinus and angiofollicular hyperplasia?

Answer 25

Sinus: Sinus histiocytosis with massive lymphadenopathy - Rosai-Dorfman disease Angiofollicular hyperplasia - Castleman's disease

Question 26

What are the two types of Castleman's disease? What is usually associated with second type, and their overall clinical course?

Answer 26

1. Unicentric - localized angiofollicular hyperplasia - indolent, benign course 2. Multicentric - multicenter angiofollicular hyperplasia -HHV-8-associated, aggressive, lymphoma-like course

Question 27

What pathological subtype of Castleman's disease is most associated with unifocal castleman's disease (UCD)? What are its features

Answer 27

Hyaline vascular type - > onion peel mantle zone - > Lollipop appearance - radially penetrating sclerotic vessels - > lots of pink, acellular material

Question 28

What pathological subtype of Castleman's disease is most associated with multifocal castleman's disease (MCD)? What are its features, and how is it treated?

Answer 28

Plasma cell / plasmablastic type - IL-6 driven (cytokine) - > Sheets of plasma cells - > more aggressive course, treated like myeloma

Question 29

What are the events in the pathogenesis of Castleman's disease?

Answer 29

Viral homologue of IL-6 drives B cell proliferation Infected B cells localize to mantle zone of LN follicles, and cytokine release contributes to constitutional symptoms

Question 30

What are the treatments for UCD and MCD?

Answer 30

UCD - surgical resection | MCD - Rituximab, corticosteroids, antiviral agents

Question 31

What is the definition of splenomegaly?

Answer 31

>14cm span in the mid-clavicular line

Question 32

What are the criteria for hypersplenism and its underlying pathophysiology?

Answer 32

1. Splenomegaly 2. Reduction of at least one cell line in the blood 3. Normal bone marrow function -> spleen is enlarging due to sequestering more WBCs/RBCs

Question 33

What are the indications for splenectomy?

Answer 33

Splenic rupture Chronic immune thrombocytopenia Hemolytic anemias - hereditary spherocytosis, AIHA, thalassemia major or intermedia Hypersplenism (in symptomatic patients)

Question 34

What must be done prior to splenectomy?

Answer 34

Pneumococcal vaccination at least two weeks before, annual flu shots, and meningococcal vaccine