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MBBS IV - Junior Clerkship WCS > JC49 (Medicine) - Lymphadenopathy and Lymphoma > Flashcards

JC49 (Medicine) - Lymphadenopathy and Lymphoma Flashcards

1
Q

Ddx generalized lymphadenopathy

A
  • Lymphoma: Low-grade cause wax-and-wane LN, High-grade cause rapidly growing masses
  • Lymphoid Leukaemia, eg. CLL, ALL (less common in AML/CML)
- Infections:
Viral, eg. IM, CMV, HIV, EBV
Bacterial, eg. TB, brucellosis, syphilis, Typhoid fever
Protozoal, eg. toxoplasmosis
Fungal: Cryptococcus
  • Connective tissue disease, eg. RA, SLE
  • Infiltration, eg. sarcoidosis, amyloidosis
  • Drugs, eg. phenytoin**, hydralazine
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2
Q

Ddx Localized lymphadenopathy

A

Localized lymphadenopathy

  • Local infection
  • Metastasis from solid tumors
  • Lymphoma, esp Hodgkin’s lymphoma
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3
Q

Describe lymphadenopathy

  • Sites
  • Size cut-off
  • Consistencies
  • Fixation
  • Overlying skin changes
A

Site:

  • Localized in local infection and early lymphoma
  • Generalized in late lymphoma

Size:
- Large (>1cm) usually abnormal

Consistency:

  • Hard: carcinoma deposits
  • Soft: may be normal
  • Rubbery: may be due to lymphoma

Tenderness: indicates infection or acute inflammation

Fixation:
- Fixed: more likely to be infiltrated by carcinoma

Overlying skin:

  • Inflammation indicates infection
  • Tethering indicates carcinoma
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4
Q

List all lymph node groups and their drainage sites in body

A
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5
Q

Causes of submental and submandibular lymphadenopathy

A
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6
Q

Causes of Jugular, Posterior cervical and suboccipital lymphadenopathy

A
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7
Q

Causes of pre- and post-auricular Lymphadenopathy

A
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8
Q

Causes of supraclavicular and axillary lymphadenopathy

A
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9
Q

Causes of epitrochlear lymphadenopathy

A
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10
Q

Causes of Inguinal lymphadenopathy

A
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11
Q

History taking for lymphadenopathy

A

History:
LN itself: rapidly enlarging, tender (reactive) vs painless, rubbery/hard (malignant)

Localizing symptoms to suggest infection, malignancy

Constitutional symptoms, eg. fever, weight loss, night sweats

Relevant infective exposure, eg. cats, insect bite, travelling, venereal exposure, IVDU

Medications, eg. phenytoin

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12
Q

Physical exam for LN

A 
Nature of LN: 
site, size (>1cm abnormal)
consistency (hard vs rubbery vs soft), 
fixation (mobile vs fixed vs matted), 
tenderness (indicates rapid enlargement with capsule stretching)

Inspect and palpate drainage basin, eg. oral cavity, thyroid, parotid, external auditory meatus…

Other relevant signs, eg. hepatosplenoegaly, tonsils (also part of lymphoid system), abdominal mass, SVCO (if any)

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13
Q

Ddx lymphadenopathy based on consistency

A

Hard: solid malignancy, previous infl’n with fibrosis

Firm, rubbery: lymphoma, chronic leukaemia

Soft: acute leukemia, reactive

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14
Q

First-line investigations for lymphadenopathy

A

CBC/D, viral studies, serology

Imaging (CXR, USG, CT, MRI)

Biopsy:
- Fine-needle aspiration cytology (FNAC): cytological information only, useful in infection and solid organ malignancies (USELESS in lymphoma)

  • Core-needle biopsy or incisional biopsy: provides histological information, useful for lymphoma
  • Excisional biopsy: architectural details required for diagnosis of lymphoma
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15
Q

Ddx atypical lymphocytosis/ infectious mono- like syndrome

A

Viral infections: EBV, CMV, HIV, acute viral hepatitis

Bacterial: atypical organisms e.g. Mycoplasma pneumoniae, Legionella penumophila, Salmonella, Rickettsia

Mycobacterial: Disseminated TB

Dimorphic fungi: Talaromyces marneffei

Parasitic: Toxoplasma gondii

Drug reaction/ hypersensitivity

Acute lymphoblastic leukemia

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16
Q

Investigations for atypical lymphocytosis

A

PBS - atypical lymphocytes

Microbiology workup:
- Blood culture
- Sputum culture and AFB smear

Specific bacterial tests:
- Mycoplasma serology
- Urine for RAT against Legionella Antigen
- Widal’s test (salmonella)

Specific viral tests:
- CMV IgG and IgM and pp65
- Monospot test and EBV serology test (EBV DNA)
- HIV antibody test

Parasite:
- Toxoplasma serology test

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17
Q

Ddx mediastinal mass

A
  1. Lymph node enlargement: Lymphoma, Metastatic LN
  2. Thymoma
  3. Germ cell tumor
  4. Retrosternal goiter
  5. Dilated aortic arch (e.g. syphilis)
  6. Neurofibroma
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18
Q

Categorize Lymphomas

A
19
Q

Describe the B-cell maturation process and lymphoid tissue involved

A
20
Q

List Precursor B-cell neoplasms

A

B-lymphoblastic leukaemia

B-lymphoblastic lymphoma

21
Q

List Pre-GC, GC and post-GC B-cell neoplasms

A
22
Q

Describe the T-cell maturation process and lymphoid tissues involved

A
23
Q

List T cell neoplasms

A

Precursor T cells:
T-lymphoblastic lymphoma/ leukaemia

Mature T cells:
Peripheral T-cell and NK-cell lymphomas/ leukaemia

24
Q

Risk factors for lymphoma development **(Non-Hodgkin HL)

A

Viral infections:

  • EBV: Hodgkin, DLBCL, Burkitt lymphoma
  • HIV: HL, BCL
  • HTLV-1: Adult T cell lymphoma/ leukaemia
  • HCV: marginal zone B cell lymphoma
  • HHV-8: primary effusion lymphoma (large BCL)

Bacterial infections: extra-nodal B cell lymphomas

  • Helicobacter pylori - Gastric lymphoma (MALT)
  • Chlamydia psittaci - Occular Adnexal Lymphoma

Immunocompromised states:

  • Congenital immunodeficiency
  • Acquired immunodeficiencies (e.g. HIV, drugs, organ transplant…etc)
  • Autoimmune diseases: RA, SLE, Sjogren syndrome …etc

Environmental/ occupational:
- pesticides, hair dyes, dioxins

25
Q

7 aims of investigations for lymphomas

A
  1. Accurate diagnosis
  2. Staging
  3. Detect complications of lymphoma
  4. Determine prognosis
  5. Determine suitability/ fitness for treatment
  6. Detect complication of treatment
  7. Assess response to treatment
26
Q

Basic investigations and rationale for DIAGNOSIS of LYMPHOMA

A

CBC with diff.
LFT/ RFT (for AKI secondary to TLS, drug adjustment for CKD)
Serum electrolytes, LDH and urate (Risk of TLS, Proliferative index)

CXR (mediastinal involvement, risk of reactivation of chronic infections)

ESR (prognosis for Hodgkin’s)
B2- microglobulin (prognosis for Follicular lymphoma)

Serum protein electrophoresis (paraproteinaemia)

BM aspiration and trephine Bx (Staging)**
PET-CT with FDG (Staging)

27
Q

Ddx precursor lymphoid cell neoplasm

A

Precursor B lymphoblastic leukaemia/lymphoma

Precursor T lymphoblastic leukaemia/lymphoma

28
Q

Ddx mature B cell neoplasms

A

Pre-GC:
Mantle cell lymphoma (MCL)

GC:
Follicular lymphoma (FL)
Burkitt lymphoma (BL)
Diffuse large B cell lymphoma (DLBCL)
Nodular lymphocyte-predominant HL
Classic Hodgkin lymphoma

Post-GC:
Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)
Marginal zone B cell lymphoma (MZL)
Lymphoplasmacytic lymphoma (Waldestrom macroglobulinaemia, WM, LPL)

Terminally differentiated:
Plasma cell neoplasms

29
Q

Ddx mature T-cell lymphoma

A 
Peripheral T cell lymphoma (PTCL)
Anaplastic large cell lymphoma (ALCL)
Adult T-cell lymphoma/leukaemia (ATL)
T cell large granular lymphocyte leukaemia (LGL)
T cell prolymphocytic leukaemia (T-PLL)
30
Q

Ddx mature NK cell lymphomas

A

NK cell large granular lymphocyte leukaemia (LGL)

Aggressive NK cell leukaemia

31
Q

Outline in detail: Staging system for lymphomas

A

Ann-Arbor Staging:

I:
Involvement of single LN region (eg. cervical, axillary, inguinal, mediastinal) or lymphoid structure (eg. spleen, thymus, Waldeyer’s ring).

II
Involvement of ≥2 LN regions or lymphoid structures on the same side of diaphragm.

III
Involvement of LN regions or lymphoid structures on both sides of diaphragm.
III.1 – involvement of spleen, splenic hilar, coeliac or portal nodes
III.2 – involvement of para-aortic, iliac, inguinal or mesenteric nodes

IV
Diffuse or disseminated involvement of ≥1 extralymphatic organs

32
Q

Investigation and rationale for PRE-TREATMENT ASSESSMENT OF LYMPHOMA

A
  1. ECG and transthoracic echocardiogram: risk of cardiotoxicity with anthracyclines
  2. Lung function studies: risk of pulmonary fibrosis with bleomycin + Immune-mediated pneumonitis with Checkpoint inhibitors
  3. Hep. B and C serology: reactivation with immunosuppression
  4. HIV serology: HIV-AIDS close link with lymphoma
  5. G6PD assay: oxidative hemolysis with co-trimoxazole/ recombinant urate oxidase - Rasburicase
33
Q

Hodgkin’s lymphoma

  • Demographics
  • S/S
  • Subtypes
  • Which subtype has young age of presentation?
A
  • Bi-modal age distribution: Late adolescence/young adulthood + old age, M>F
  • S/S:

Painless lymphadenopathy at neck and chest, fluctuates in size with URTI symptoms
Incidental mediastinal mass or compressive SOB, cough, chest apin
Moderate splenomegaly +/- hepatomegaly
Late skin involvement
Fever, drenching night sweats, general pruritis

Subtypes:
1. Classical HL:
- Nodular sclerosis* - classical Reed-Sternberg cells with Eosinophilia
- Lymphocyte rich
- Lymphocyte depleted
- Mixed cellularity
2. Nodular lymphocyte-predominant type: No Reed-Sternberg cells, tumor B cell predominant

*Nodular Sclerosis Classical HL has young age of presentation (15-35)

34
Q

Hodgkin lymphoma

Treatment

A

ABVD = doxorubicin (Adriamycin), bleomycin, vinblastine, dacarbazine
± Radiotherapy

Salvage combination chemo (eg. ICE, GVD) followed by autologous HSCT

35
Q

Diffuse Large B-cell lymphoma

  • Define classification
  • Most associated disease
  • Gene mutation
  • S/S
  • Treatment
A
  • Most common Non-Hodgkin Lymphoma
  • AIDS-DEFINING MALIGNANCY
  • CREBBP* mutation (chromatin remodeling), EZH2 and MYC

S/S: Defined to organs: e.g. Primary CNS or Primary Mediastinal DLBCL
- Rapidly enlarging mass: most commonly neck/abdominal
- Late extranodal involvement:
GI - anorexia, pain, fullness, GIB;
CNS: headache, focal neurological, seizures…etc
- B sypmtoms: Fever, night sweats, Weight loss
- Bone marrow involvement (rare)
- Compressive symptoms: SVCO, cord compression, airway

Treatment:
R-CHOP, EPOCH-R for double hit DLBCL
Auto-HSCT for chemosensitive relapse,
CAR T-cell therapy for CD19+ DLBCL

36
Q

Burkitt lymphoma

Genetic cause

S/S

Treatment

A

Genetics:
Deregulated expression of cMYV due to reciprocal translocation with Ig heavy chain t(8;14), or variant light chain gene loci t(2;8) or t(8;22)

S/S:

  • Large abdominal mass
  • B-symptoms: fever, night sweats, weight loss
  • Extra-nodal involvement with BM infiltration
  • Leptomeningeal involvement

Treatment:
Rituximab + combination chemotherapy
TLS

37
Q

Follicular lymphoma

Genetic cause
S/S
Treatment

A

Low-growing or indolent form of non- Hodgkin lymphoma (NHL)

Genetics:
t(14;18), CREBBP, MLL2 mutations (chromatin remodeling)

S/S: non-specific, late advanced presentation

  • Lymphadenopathy
  • B symptoms: fever, night sweat, weight loss

Treatment:
Anti-CD20 mAb + Purine analogue/ alkylating agent chemotherapy

38
Q

Marginal zone B-cell lymphoma

  • Cause
  • Classification
  • Associated infections/ condition
  • Treatment
A

Caused by chronic antigenic stimulation by microbial pathogens or autoantigens/ Autoimmune disease

Extranodal MZL or Mucosa-Associated Lymphoid Tissue (MALT)most common

  • Gastric MALT (H.pylori)
  • Cutaneous MALT (B. burgdorferi or B afzeli)
  • Ocular adnexal MALT (C. psittaci)
  • Pulmoanry or parotid MALT (Sjogren syndrome)
  • Thyroid MALT (Hasimoto thyroiditis)

Nodal MZL (Hepatitis C)

Splenic MCL/ SMZL (hepatitis C)

Treatment:
Gastic MALT: triple therapy for H. pylori, Radiation, Anti- CD20 mAb
Non-gastric MALT: Radiation, doxycycline, Anti-CD20 mAb, Bedndamustine +/- R-CHOP
Nodal MZL: Radiation, chemo, immunotherapy
Splenic MZL: Ibrutinib, Lenalidomide, Anti-CD20 mAb

39
Q

Lymphoplasmacytic lymphoma

  • Cell origin
  • Types
  • S/S
  • Defining feature
  • Treatment
A

Lymphoplasmacytic lymphoma

  • Waldestrom macroglobulinaemia or LPL
  • Post-germinal centre IgM memory B cell before isotype class switching, MYD88 mutation***
  • IgM monoclonal gammopathy ***

S/S:

Hyperviscosity syndrome
Peripheral neuropathy
Cryoglobulinaemia
BM infiltration: anaemia and bleeding tendency 
Lymphadenopathy 
Hepatosplenomegaly

Treatment:

  • Emergency plasmapheresis for hyperviscosity syndrome
  • Rituximab + chemotherapy
40
Q

Mantle cell lymphoma

Demographic
Cell of origin
Genetic Cause
S/S

A

Mid-60s, male-predominant

Subtype of NHL
t(11; 14), ATM, TP53 and chromatin modification mutations, alter cyclin D1

naïve, pre-germinal centre B lymphocytes

S/S

  • Special invasion of GIT - Lymphomatous polyposis of large bowel
  • Extra-nodal involvement: BM infiltration
  • Lymphadenopathy
  • B symptoms
41
Q

CLL/SLL
Chronic lymphocytic leukaemia/ Small lymphocytic lymphoma

  • Demographics
  • S/S
  • Staging system
A

Most prevalent lymphoid neoplasm in North America and Europe
Median age 72, M:F = 2:1

S/S:
Largely asymptomatic, incidental find 
Leukocytosis/ lymphocytosis
Lymphadenopathy 
Splenomegaly 
Anemic and thrombocytopenia S/S

Staging:
Binet staging/ Rai staging

42
Q

Extra-nodal NK/ T-cell lymphoma

  • Demographic
  • Risk factors
  • Cells of origin
  • S/S
  • Treatment
A

Demographic:
Asian, with EBV infection
Exposure to pesticides and chemical solvents

NK- or γδ T-cell
CD2, cytoplasmic CD3 (CD3ε), CD45, NK-cell marker CD56

S/S: 
Nasal, Palatal ulcer or perforation 
Nasal obstruction
Bloody rhinorrhea 
swelling of cheek or orbit, sore throat, and hoarseness
Fever and night sweats

Tx:
SMILE: dexamethasone, methotrexate, ifosfamide, L-asparaginase and etoposide

43
Q

Spectrum of treatments for lymphomas (list general classes of drugs/ treatment)

A

Pharmacological options: Multi-agent chemotherapy +/- monoclonal antibodies

  • Targeted therapy: BTK/ BCL-2 inhibitors
  • Immuno-conjugates
  • Checkpoint inhibitors
  • Chimeric antigen receptor T cell therapy

Transplant:
- Autologous HSCT

Supportive:

  • Prevention of TLS (e.g. recombinant urate oxidase)
  • Management of disease/ Tx complications

MBBS IV - Junior Clerkship WCS (131 decks)

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