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

JC49 (Medicine) - Lymphadenopathy and Lymphoma Flashcards

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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

19
Q

Describe the B-cell maturation process and lymphoid tissue involved

20
Q

List Precursor B-cell neoplasms

Study These Flashcards
A

B-lymphoblastic leukaemia

B-lymphoblastic lymphoma

21
Q

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

22
Q

Describe the T-cell maturation process and lymphoid tissues involved

23
Q

List T cell neoplasms

Study These Flashcards
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)

Study These Flashcards
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
7 aims of investigations for lymphomas
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
Basic investigations and rationale for DIAGNOSIS of LYMPHOMA
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
Ddx precursor lymphoid cell neoplasm
Precursor B lymphoblastic leukaemia/lymphoma Precursor T lymphoblastic leukaemia/lymphoma
28
Ddx mature B cell neoplasms
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
Ddx mature T-cell lymphoma
``` 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
Ddx mature NK cell lymphomas
NK cell large granular lymphocyte leukaemia (LGL) | Aggressive NK cell leukaemia
31
Outline in detail: Staging system for lymphomas
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
Investigation and rationale for PRE-TREATMENT ASSESSMENT OF LYMPHOMA
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
Hodgkin's lymphoma - Demographics - S/S - Subtypes - Which subtype has young age of presentation?
- 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
Hodgkin lymphoma Treatment
ABVD = doxorubicin (Adriamycin), bleomycin, vinblastine, dacarbazine ± Radiotherapy Salvage combination chemo (eg. ICE, GVD) followed by autologous HSCT
35
Diffuse Large B-cell lymphoma - Define classification - Most associated disease - Gene mutation - S/S - Treatment
- 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
Burkitt lymphoma Genetic cause S/S Treatment
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
Follicular lymphoma Genetic cause S/S Treatment
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
Marginal zone B-cell lymphoma - Cause - Classification - Associated infections/ condition - Treatment
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
Lymphoplasmacytic lymphoma - Cell origin - Types - S/S - Defining feature - Treatment
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
Mantle cell lymphoma Demographic Cell of origin Genetic Cause S/S
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
CLL/SLL Chronic lymphocytic leukaemia/ Small lymphocytic lymphoma - Demographics - S/S - Staging system
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
Extra-nodal NK/ T-cell lymphoma - Demographic - Risk factors - Cells of origin - S/S - Treatment
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
Spectrum of treatments for lymphomas (list general classes of drugs/ treatment)
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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