Lymphadenopathy and Lymphocytosis (Small Group Session 26) Flashcards

1
Q

What 5 features of lymph nodes do you assess during physical exam? And what might some of these features be associated with?

A
  1. Location: consider drainage area
  2. Size: abnormal is generaly >1cm
  3. Consistency: hard may be carcinoma, rubbery may be lymphoma, fluctuant (push on them and they give) may be infectious
  4. Fixation: normal nodes are freely mobile
  5. Tenderness: often inflammatory, but may be mailgnant
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2
Q

What are the approximate proportions (%) of T cells, B cells and NK cells in the blood?

A

T cells (CD3+ cells) 75%

B cells (CD20+ cells) 15%

NK cells (CD56+ cells) 5%

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3
Q

Which tests are required for the diagnosis of Chronic Lymphocytic Leukemia (CLL)?

A) bone marrow aspirate +/- biopsy

B) physical examination demonstrating lymphadenopathy

C) flow cytometry of the peripheral blood

D) cytogenic analysis (of peripheral blood or bone marrow)

E) physical exam or radiological imaging showing splenomegaly

A

C) flow cytometry of the peripheral blood (CD5, CD20, CD23 etc)

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4
Q

What are the common clinical features in patients with CLL?

A

Clinical Features

  • 25% are asymptomatic
  • Incidental lymphocytosis
  • +/- B symptoms
  • Lymphadenopathy
  • Splenomegaly
  • Anemia (fatigue, SOB)
  • Infection (particularly encapsulated organisms)
  • Bleeding (ITP, AIHA)
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5
Q

What are the reasons for thrombocytopenia and anemia secondary to CLL?

A
  • Splenic sequestration of platelets
  • Bone marrow infiltration
  • Autoimmune process related to abnormal B cell function
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6
Q

Which of the following patients requires chemotherapy to treat his/her CLL?

A) Mr. S with a WBC of 300 (4-11) noted on routine blood work - Hgb 138 (137-180), platelets 155 (150-400) - asymptomatic

B) Mrs. S with a WBC of 30 and multiple palpable lymph nodes (Hgb/platelets normal) - anxious about lymph nodes

C) Mr. X with a WBC of 14, Hgb 120, platelets 120, noted on routine bloodwork, asymptomatic

D) Mrs. X WBC 30, Hgb 100, platelets 100, with progressive lymph nodes and generalized malaise, weight loss

A

D) Mrs. X WBC 30, Hgb 100, platelets 100, with progressive lymph nodes and generalized malaise, weight loss

Indications for Treatment

  • Lymphocyte doubling time of less than 6 months
  • Systemic symptoms
  • Symptomatic lymphadenopathy or splenomegaly
  • Significant anemia (Hgb <110) or thrombocytopenia (platelets <100)
    • From bone marrow involvement
    • Autoimmune
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7
Q

Which of the following are features of chronic lymphocytic leukemia?

A) a chronic proliferation of mature T cells

B) an indolent disease that most people “die with and not of”

C) CLL has a prognosis of only 4-5 years in someone who presents with significant thrombocytopenia

D) CLL has a typical immunophenotype which can be identified with flow cytometry of the peripheral blood

A

D) CLL has a typical immunophenotype which can be identified with flow cytometry of the peripheral blood

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8
Q

A 58 yr M visits your office with fevers, nigh sweats, and a complaint of an enlarging mass on the R side of his neck. He has noticed that the lump has increased in size steadily over the past week. He is otherwise healthy and is on no medications. The remainder of the review of systems is unremarkable. Physical examination reveals a 5 x 8cm mass in the right anterior cervical chain. The mass is non-tender. Examination also reveals enlarged lymph nodes in the left anterior cervical chain, left axilla and bilateral inguinal regions. His spleen is palpable 8 cm below the left costal margin. CBC is normal.

What are the important clinica findings in this case and what do they suggest? How do you proceed to make the diagnosis?

A

Clinical Features

  • B symptoms: fevers, night sweats
  • Large mass in R anterior cervical chain
  • Diffuse lymphadenopathy, non-tender
  • Splenomegaly

These findings suggest malignancy. The next step is to biopsy the lymph node to look for Reed-Sternberg cells to differentiate Non-Hodgkin’s and Hodgkin’s lymphoma. X-rays and CT scan are completed to determine the stage of cancer.

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9
Q

A 58 yr M visits your office with fevers, nigh sweats, and a complaint of an enlarging mass on the R side of his neck. He has noticed that the lump has increased in size steadily over the past week. He is otherwise healthy and is on no medications. The remainder of the review of systems is unremarkable. Physical examination reveals a 5 x 8cm mass in the right anterior cervical chain. The mass is non-tender. Examination also reveals enlarged lymph nodes in the left anterior cervical chain, left axilla and bilateral inguinal regions. His spleen is palpable 8 cm below the left costal margin. CBC is normal. A lymph node biopsy does not reveal Reed-Sternberg cells.

What is your diagnosis?

A

Non-Hodgkin’s Lymphoma is non-Reed-Sternberg lymphoma.

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10
Q

What is the name of this cell? What is its presence associated with?

A

Reed-Sternberg cells are found in smears from Hodgkin’s Lymphoma patients.

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11
Q

What is the clinical presentation of Hodgkin Lymphoma? At what age(s) does it it typically present?

A

Hodgkin Lymphoma

  • Bimodal distribution of presentation with peaks at <20 yrs and >50 yrs
  • Associated with Epstein-Barr virus in up to 50% of cases, causal role not determined

Clinical Features

  • Asymptomatic lymphadenopathy (70%)
    • Non-tender, rubbery consistency
    • Cervical/supraclavicular (60-80%), axillary (10-20%), inguinal (6-12%)
    • Lymph node pain with alcohol
  • Splenomegaly +/- hepatomegaly
  • Mediastinal mass
    • Found on routine CXR, may be symptomatic (cough)
  • B symptoms
  • Spreads in orderly fashion
    • Starts at a single site in lymphatic system (node) , spreads first to adjacent nodes
  • +/- Pruritus
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12
Q

What is the clinical presentation of Non-Hodgkin Lymphoma?

A

Non-Hodgkin Lymphoma (NHL)

  • Older people
  • Strongly associated with infections (EBV) and immunosuppresion (HIV)

Clinical Presentation

  • Painless lymphadenopathy, usually >1 LN region
  • B symptoms less common
  • Abdominal signs
    • Hepatosplenomegaly
  • Oropharyngeal involvement: sore throat and obstructive apnea, raspy voice
  • Pruritis
  • Cytopenia: anemia +/- neutropenia +/- thrombocytopenia can occur when bone marrow is involved
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13
Q

An 18 yr F presents with fevers, sore throat and general malaise. Clinical examination reveals bilateral enlarged upper cervical lymph nodes which are tender to palpate. Pharynx is red. The rest of the examination is unremarkable. CBC: Hemoglobin 145 g/L, WBC 18 x 109/L with 70% lymphocytes, 22% neutrophils, 6% monocytes, 2% eosinophils. Platelets 180 x 109/L.

What testing would you complete and what would you be looking for?

A
  • Query EBV (Mononucleosis)
  • Investigations: PBS (atypical lymphocytes), monospot, EBV, CMV, HIV serology (IgG and IgM), flow cytometry
  • Polyclonal
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14
Q

A 68 yr F presents for a routine health examination after several years without seeing a doctor. She is feeling well and her review of systems is negative. Physical examination reveals some small lymph nodes in the right axilla, left groin and splenomegaly 2 cm below the costal margin. CBC: Hemoglobin 125 g/L, MCV 89 fL, WBC 75 x 109/L and platelets 110 x 109/L. On the differential 85% of white cells are lymphocytes.

What is the most probable diagnosis and how would you confirm it?

A

Chronic Lymphocytic Leukemia

Diagnosis

  • Blood count and smear (looking for smudge cells)
  • Immunophenotype and flow cytometry ( CD5, CD19, CD23, Dim CD20, CD200+)
  • >5 x 109/L lymphocytes in peropheral blood for >3 months
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15
Q

What is the clinical presentation of CLL and what age group is it most likely to present in?

A

Chronic Lymphocytic Leukemia

  • Most common adult leukemia in the Western world
    • Accounts for 40% of all leukemias in patients >65 yrs
  • Incidence increases with age

Clinical presentation

  • 25% asymptomatic (incidental lymphocytosis finding)
  • 5-10% present with B symptoms
  • Anemia
  • Lymphadenopathy
  • Splenomegaly
  • Infection
  • Immune disregulation: autoimmune hemolytic anemia (Coombs positive), ITP, hypogammaglobulinemia +/- neutropenia
  • +/- bleeding and bruising
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16
Q

A 68 yr F presents for a routine health examination after several years without seeing a doctor. She is feeling well and her review of systems is negative. Physical examination reveals some small lymph nodes in the right axilla, left groin and splenomegaly 2 cm below the costal margin. CBC: Hemoglobin 125 g/L, MCV 89 fL, WBC 75 x 109/L and platelets 110 x 109/L. On the differential 85% of white cells are lymphocytes.

Why is this patient thrombocytopenic?

A

Thrombocytopenia in CLL

  • Spleen sequestration
  • Bone marrow involvement (infiltration)
  • Autoimmune process related to abnormal B cell function
17
Q

A 68 yr F presents for a routine health examination after several years without seeing a doctor. She is feeling well and her review of systems is negative. Physical examination reveals some small lymph nodes in the right axilla, left groin and splenomegaly 2 cm below the costal margin. CBC: Hemoglobin 125 g/L, MCV 89 fL, WBC 75 x 109/L and platelets 110 x 109/L. On the differential 85% of white cells are lymphocytes.

What would your approach to treatment be with this patient?

A

The patient is asymptomatic and does not have any red flags for indication for treatment. Therefore, this patient simply requires monitoring for the time being.

Indications for Treatment in CLL

  • Lymphocytic doulbing time in <6 mths
  • Systemic symptoms
  • Symptomatic lymphadenopathy or splenomegaly
  • Significant anemia (Hemoglobin <110) or thrombocytopenia (platelets <100)
18
Q

What is the significance of these cells?

A

Smudge Cells

  • Classic in CLL but NOT diagnostic
  • Smudge cells are abnormally fragile and are therefore damaged during the slide creation process
19
Q

What diagnosis is this smear consistent with?

A

Chronic Lymphocytic Leukemia

  • Lymphocytosis
  • Lymphocytes look very similar to normal lymphocytes but there are too many of them
20
Q

What therapies are available for CLL patients?

A

CLL Therapy

Traditional cytotoxic chemotherapy

  • Chlorambucil (alkylator)
  • Fludarabine (purine analog)

Monoclonal antibody

  • Rituximab (anti CD20)
  • Alemtuzumab (anti CD52)

Novel agents

  • Bruton’s tyrosine kinase inhibitor
  • P13kinase delata inhibitor
  • BCL2 inhibitor