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MBBS II HIS > L20- Lymphomas – principles of diagnosis and management > Flashcards

L20- Lymphomas – principles of diagnosis and management Flashcards

1
Q

Define lymphoma

A

neoplasm/ Clonal malignancy of the lymphoid system

Typically mature** lymphoid neoplasm

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2
Q

Classify broad types of lymphomas by cell of origin?

A
  1. B cells: B cell lymphoma:
    Rearranged IgH gene in stem cell&raquo_space; clonal rearrangement of IgH
  2. T cells: T cell lymphoma:
    Rearranged TCR gene in stem cell&raquo_space; clonal rearrangement of TCR
  3. Natural killer (NK) cells&raquo_space; NK cell lymphoma
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3
Q

List some precursor B cell neoplasms?

A

B lymphoblastic leukemia/ lymphoma

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4
Q

List some Pre-germinal center B cell neoplasms

A

Mantle cell lymphoma

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5
Q

List some germinal center B cell neoplasms?

A

Follicular lymphoma

Burkitt lymphoma

Diffuse large B cell lymphoma

Hodgkin lymphomas

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6
Q

List some post- germinal center B cell neoplasms?

A 
Marginal zone (MALT) lymphoma 
Lymphoplasmacytic lymphoma 
CLL/SLL
Diffuse large B-cell lymphoma 
Plasmacytoma
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7
Q

Classify lymphoma by neoplastic behavior.

A

1) B cell lymphomas + B - lymphoproliferative diseases
a) High grade or Low-grade B cell lymphomas/ BLPD

2) T-cell lymphomas
3) NK/T cell lymphomas

4) Hodgkin lymphoma
a) Classical HL
b) Nodular lymphocyte predominant HL

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8
Q

List examples of high grade and low grade B cell lymphomas?

A

High grade = DLBCL, Burkitt lymphoma

Low grade = Follicular lymphoma, chronic B-LPD i.e. CLL

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9
Q

Difference between high grade and low grade B cell lymphoma in presentation?

A

High = Rapid proliferation, acute onset with severe symptoms

Low = Indolent, late-stage presentation with moderate symptoms

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10
Q

Which viral infections are asso. with T cell lymphomas?

A

EBV*** = asso. with NK cell lymphomas

HTLV-1
HIV

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11
Q

Age group affected by lymphomas?

A

Typical = adults after 4th decade

Extremely rare in children/ young adults

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12
Q

List some general symptoms of lymphoma?

A

 Unexplained fever > 38oC (because inflammatory)

 Night sweats

 Unintentional loss of > 10% body weight in 6 months

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13
Q

Fine-needle aspiration of affected lymph nodes is adequate for lymphoma investigation. T or F?

A

False

Simple cytological exam not acceptable

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14
Q

Describe the sequence of investigations for lymphoma? (from dx to treatment)

A
  1. Accurate Dx by clinical, morphological, immunophenotypic and genetic features
  2. Staging for prognosis, complications + choose treatment
  3. Determine suitability or fitness for treatment
  4. Detect response and complications to treatment
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15
Q

List the blood metrics that are investigated in lymphoma?

A

General:

  • CBC
  • Serum electrolyte levels (Na, K, Ca, PO4)
  • LDH and urate levels (tumor lysis syndrome)

Specific:

  • ESR (marker for early classical HL)
  • β2-microglobulin (marker for follicular lymphoma)
  • Serum protein electrophoresis used for finding para-proteins
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16
Q

List expected abnormal blood findings in tumour lysis syndrome?

A
  • Very high K+, PO4, Urate, LDH

- Low Ca

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17
Q

Define tumour lysis syndrome?

A

when a large number of cancer cells die within a short period (i.e. by chemotherapy), releasing their contents in to the blood

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18
Q

List some radiological exams for lymphoma investigation?

A
  • CXR (to look for disease-related complications, active or prior infections)
  • PET-CT for staging
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19
Q

List some investigation for staging of lymphoma?

A

PET-CT

Bone marrow aspiration and trephine biopsy

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20
Q

Name the system used to stage lymphomas?

A

Ann Arbor Staging

4 stages

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21
Q

Describe stage 1 lymphoma in Ann Arbor Staging?

A

Involvement of Single lymph node region or single extralymphatic site

22
Q

Describe stage 2 lymphoma in Ann Arbor Staging?

A

Involvement of TWO OR MORE lymph node regions on the SAME SIDE of the diaphragm

May include localized extra-lymphatic region

23
Q

Describe stage 3 lymphoma in Ann Arbor Staging?

A

Involvement of lymph node regions on BOTH SIDES of the diaphragm

May include spleen or localized extralymphatic regions

24
Q

Describe stage 4 lymphoma in Ann Arbor Staging?

A

DIFFUSE EXTRALYMPHATIC disease

e.g. in liver, BM, lung, skin…

25
Q

List the investigations for suitability or fitness for treatment for lymphoma? Explain why these tests are done?

A

Due to chemo drug ADR:

  • ECG, transthoracic echocardiogram (doxorubicin cardiotoxicity)
  • Lung function study (MTX lung, pulmonary fibrosis from bleomycin)
  • Hep. B and C serology (reactivation after immunosuppressant)
  • HIV serology (concurrent feature)
  • G6PD assay (Oxidative hemolysis from Co-trimoxazole)
26
Q

Main treatment modality of lymphoma? ***

A
  • Multi-agent cytotoxic chemotherapy +/- monoclonal antibodies +prevention of tumour lysis syndrome and complications
  • Multi-cycle with interim and end assessments

i. e. R- CHOP
- Rituximab (mAb)
- Cyclophosphamide (alkylating)
- Doxorubicin (anthracycline)
- Vincristine (plant derivative)
- Prednisolone (steroid)

27
Q

Which patients with lymphoma is indicated for HSCT?

A

autologous HSCT

selected relapsed patients who are chemo-sensitive

28
Q

List 2 types of drugs used against less typical types of lymphoma?

A

Immuno-conjugates

Checkpoint inhibitor

29
Q

Diffuse Large B Cell Lymphoma: clinical presentation?

A
  • Unintentional weight loss
  • Rapidly enlarging, firm, non-tender lymph nodes typically in neck, abdomen, mediastinum
  • Extranodal involvement is common in GIT
  • Fever, night sweat possible
30
Q

Histological features of DLBCL lymph nodes?

A
  1. Effaced nodal architecture, loss of follicular structure
  2. Sheets of large abnormal, hypermetabolic lymphoid cells
31
Q

What is the expected immunohistochemistry findings in DLBCL?

A

CD19+, CD20+, CD79a+, PAX5+.

T-cell and NK cell markers negative

32
Q

Treatment modality of DLBCL?

A

Entecavir prophylaxis
+
R-CHOP

Rituxumab + Cyclophosphamide + Doxorubicine + Vincristine + Prednisolone

33
Q

Typical presentation of Classical Hodgkins lymphoma?

A

symptomatic lymphadenopathy +/- mediastinal mass*****on chest radiography

fever, night sweats, unintended weight loss, loss of appetite

34
Q

Possible causes of mediastinal mass on CXR?

A
  • Lymphoma/ metastatic LN
  • Thymoma
  • Germ cell tumour, Neurofibroma
  • Retrosternal Goitre
  • Dilated aortic arch
35
Q

Histological features of LN in classical Hodgkin lymphoma?

A
  1. Distorted nodal architecture
  2. Typical multinucleated Reed-Sternberg cells** were present
  3. Prominent infiltration by inflammatory cells (reactive lymphocytes, eosinophils and plasma cells)
36
Q

Typical immuno-histochemical study for classical Hodgkin lymphoma?

A
  1. CD30 immunostain***** highlight the malignant Hodgkin and ReedSternberg cells
  2. negative for other B- and T cell markers
37
Q

Typical blood investigation results for classical Hodgkin lymphoma?

A
  • elevated LDH and urate
  • Eosinophilia**
  • Normal serum electrolytes
38
Q

Typical blood investigation results for DLBCL?

A
  • Grossly elevated LDH, Urate

- Normal CBC, serum electrolytes

39
Q

Typical treatment modality for classical Hodgkin lymphoma?

A

ABVD +/- Rituximab (+ Febuxostat)

Adriamycin, Bleomycin, Vinblastine, Dacarbazine

40
Q

Why is Febuxostat added to chemotherapy regimens for diff. lymphomas?

A

To manage tumour lysis syndrome

41
Q

Which chemotherapy drug can accumulate if taken with allopurinol or febuxostat?

A

6-Mercaptopurine

42
Q

Treatment modality for relapsed/ unresponsive Classical Hodgkin Lymphoma?

A

1) immuno-conjugate Brentuximab vedotin: anti-CD30 monoclonal ab linked to MMAE
(MMAE is a microtubule disrupting agent)

2) Check-point inhibitor: Pembrolizumab (anti-PD1)

43
Q

MoA of Anti-PDl or Anti-PDL-1 chemo drugs?

A

PD-L1 binds to PD-1 and inhibits T cell killing of the tumour cell

Chemo drug blocks PD-L1 or PD-1&raquo_space; allow T cell killing

44
Q

Typical clinical presentation of NK cell lymphoma?

A
  • Nasal swelling, perforation of hard palate, deviated nasal septum
  • Intermittent epistaxis for 4 weeks
  • Tumour in nasal cavity and nasopharynx with local destruction
  • RARE primary nodal presentation
45
Q

Typical histological finding in biopsy of nasal tumour in NK cell lymphoma?

A
  • neoplastic lymphoid infiltrate exhibiting angiocentricity and angiodestruction
46
Q

Typical immunohistochemical test finding for NK cell lymphoma?

A
  • CD16 and CD56 positive marker for NK

- cytoplasmic CD3ɛ, cytotoxic markers (perforin, granzyme) and Ebstein-Barr virus encoded RNA (EBER) positive

47
Q

List some clinical presentations of aggressive NK cell lymphoma?

A

fever, rash, hepatosplenomegaly, pancytopenia and hemophagocytosis

48
Q

List some non-nasal sites that may be involved in NK cell lymphoma?

A

skin, GI tract and testes

49
Q

Finding primary nodal involvement is very common for NK cell lymphomas. T or F?

A

False

Primary nodal presentation is extremely rare

50
Q

Typical treatment modality for NK cell lymphoma?

A 
Multi-drug chemo: LEMIL
\+ L-asparaginase 
\+ Etoposide (topoisomerase-I inhibitor) 
\+ Methotrexate (anti-metabolite) 
\+ Ifosfamide (alkylating) 
\+ Local irradiation

Steroids

MBBS II HIS (30 decks)

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