9a- Lymphadenopathy Flashcards

1
Q

Describe the transit of B cells into and out of the lymph node

A

Travel through:

  • bone marrow (maturation)
  • blood
  • enter lymph node through high endothelial venule (HEV)
  • migrate to cortex
  • begin in the mantle zone (naive)
  • clonal expansion in follicular germinal center in response to antigen
  • migrate to marginal zone and become memory B cells or differentiate into plasma cells
  • exit via efferent lymphatics
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2
Q

Describe the transit of T cells into and out of the lymph node

A

Travel through:

  • Thymus (maturation)
  • blood
  • enter lymph node through HEV
  • migrate to paracortex
  • clonal expansion in the paracortex in response to antigen
  • exit via efferent lymphatics
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3
Q

Describe the lymphadenopathy observed in this specimen. How severe would a patient’s fever be and would they have mono or polyclonal B/T cells?

A

Indicative of an infection (some increase in secondary follicles due to mounting of immune response)

  • localized, mild lymphadenopathy
  • low grade fever
  • polyclonal B/T cells
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4
Q

Describe the lymphadenopathy observed in this specimen. How severe would a patient’s fever be and would they have mono or polyclonal B/T cells?

A

Indicative of neoplasm (cellular atypia and no secondary follicles)

  • extensive, marked lymphadenopathy
  • drenching night sweats
  • monoclonal B/T cells
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5
Q

Describe the duration, size, location, tenderness, mobility and consistency of a benign lymphadenopathy

A
  • duration= < 2 weeks
  • size= < 2 cm (1 cm= normal)
  • location= cervical, inguinal
  • tenderness= tender
  • mobility= mobile
  • consistency= soft
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6
Q

Describe the duration, size, location, tenderness, mobility and consistency of a malignant lymphadenopathy

A
  • duration= > 2 weeks
  • size= > 2 cm (1 cm= normal)
  • location= supraclavicular
  • tenderness= non-tender
  • mobility= fixed
  • consistency= firm, hard
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7
Q

Describe the architecture, dominant cell type, atypia, and ancillary study (flow cytometry) findings of benign lymphadenopathy

A
  • architecture= intact
  • dominant cell type= small lymphs
  • atypia= none
  • ancillary study findings= polyclonal
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8
Q

Describe the architecture, dominant cell type, atypia, and ancillary study (flow cytometry) findings of malignant lymphadenopathy

A
  • architecture= effaced
  • dominant cell type= large lymphs/epithelial cells
  • atypia= present
  • ancillary study findings= monoclonal
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9
Q

What are B symptoms? What do they usually represent and how are they used?

A
  • generalized symptoms found in either reactive or neoplastic lymphadenopathy
    • fever
    • night sweats
    • weight loss (>10% body weight in 6 months)
  • usually seen in neoplasms (incorporated into staging systems for lymphoma)
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10
Q

What are some causes of reactive lymphadenopathy?

A
  • infectious
  • autoimmune
  • drugs
  • foreign body (e.g. orthopedic surgery)
  • Castleman’s disease
  • Sarcoidosis
  • Kikushi-Fujimoto
  • Kimura’s disease
  • Rosai disease
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11
Q

What are some causes of neoplastic lymphadenopathy?

A
  • lymphoma
  • leukemic involvement
    • lymphoblastic lymphoma
    • myeloid sarcoma
  • metastatic tumor (most common!)
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12
Q

What are 6 histologic patterns of reactive lymphadenopathy (and what disease processes cause them)?

A
  • follicular hyperplasia
    • autoimmune, early HIV, toxoplasmosis
  • paracortical hyperplasia
    • EBV, CMV, herpes, drugs
  • sinus histiocytosis
    • draining tumors
  • necrotizing
    • cat scratch, bacterial, fungal, autoimmune, viral
  • granulomatous
    • fungal, TB, sarcoidosis
  • mixed
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13
Q

What does this image show?

A

Follicular hyperplasia

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14
Q

What does this image show?

A

Paracortical hyperplasia

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15
Q

What does this image show?

A

Sinus histiocytosis

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16
Q

What does this image show?

A

Granulomatous inflammation

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17
Q

What are two major differentials to consider if you saw this biopsy image?

A
  • follicular lymphoma (more likely due to crowding)
  • follicular hyperplasia (benign; less likely)
18
Q

What is a common treatment plan for follicular lymphoma?

A
  • Indolent/slow growth common so early treatment may be “watchful waiting”
  • 40% of cases transform to more aggressive lymphoma (may present as increased fatigue or show on CT scan)
  • Once symptoms begin, treat with chemotherapy and anti-CD20 monoclonal antibody therapy
19
Q

Describe follicular lymphoma; what is its prevalence?

A
  • 60 yo median age, slight male predominance
  • nodal > extranodal
  • extensive, generalized adenopathy
  • 20% of all lymphomas; 1/3 of B cell lymphomas
20
Q

What is the genetic variation that common causes follicular lymphoma?

A

Most characterized by t(14;18)

21
Q

What is the disease progression of follicular lymphoma?

A
  • generally indolent
  • 40% transform to aggressive lymphomas
    • diffuse large B cell lymphoma
    • Burkitt lymphoma
22
Q

What does this image show?

A
  • “starry sky” appearance of Burkitt lymphoma
    • increased cellularity= “sky”
    • lighter macrophages= “stars”
23
Q

What are the B cell non-hodgkin lymphomas (NHLs) we need to know (6)?

A
  • follicular lymphoma
  • diffuse large B cell lymphoma
  • mantle cell lymphoma
  • marginal zone lymphoma
  • lymphoplasmacytic lymphoma
  • Burkitt lymphoma
24
Q

What are the morphologies that help differentiate the B cell NHLs?

A
  • nodular, follicular
    • follicular lymphoma
    • mantle cell lymphoma
    • marginal zone lymphoma
    • CLL/SLL
  • diffuse
    • diffuse large B cell lymphoma
    • Burkitt lymphoma
25
Q

What are the tumor sizes that help differentiate the B cell NHLs?

A
  • small
    • follicular lymphoma
    • marginal zone lymphoma
    • CLL/SLL
    • lymphoplasmacytic lymphoma
  • medium to large
    • diffuse large B cell lymphoma
    • Burkitt lymphoma
  • any size
    • mantle cell lymphoma
26
Q

What are the immunophenotypes that help differentiate the B cell NHLs?

A
  • all show B cell lineage (CD19,20)
  • CD5
      • = mantle cell and CLL/SLL
      • = follicular and marginal zone
  • then use CD10/CD23 to differentiate (see flow chart)
27
Q

What are the cytogenetics that help differentiate the B cell NHLs?

A
  • t(14;18) = follicular
  • t(11;14) = mantle cell
  • t(8;14) = Burkitt
    • also t(2;8) and t(8;22)
  • t(11;18) = marginal zone
28
Q

Describe the cellular result of the t(14;18) translocation

A
  • prevents cells from apoptosis
  • IgH - bcl2 fusion in follicular lymphoma leads to overexpression of Bcl2, preventing cells from regulating cell death
    • CELLS DON’T DIE
    • NOT increased growth (so more indolent than other lymphomas)

**diagnosis for follicular lymphoma

29
Q

Describe the cellular result of the t(11;14) translocation

A
  • cyclin D1 - IgH fusion
  • cyclin D1 overexpressed, allowing increased cell growth

**diagnosis for mantle cell lymphoma

30
Q

Describe the cellular result of the t(8;14) translocation

A
  • c-MYC - IgH fusion
  • c-MYC= oncogene
    • results in agressive proliferation when translocated next to IgH

**diagnosis for Burkitt lymphoma

31
Q

How would you grade the B cell NHLs? (low, medium, high)

A
  • low
    • CLL/SLL
    • follicular lymphoma
    • marginal zone lymphoma
    • lymphoplasmacytic lymphoma
  • medium
    • mantle cell lymphoma
  • high
    • diffuse large B cell lymphoma
    • Burkitt lymphoma
32
Q

Contrast extranodal marginal zone lymphoma and diffuse large B cell lymphoma

A
  • extranodal marginal zone lymphoma
    • indolent
    • small cells at extranodal sites (mainly MALT)
    • treatment= antibiotics (against helicobacter), immunotherapy, radiation, chemo
  • diffuse large B cell lymphoma
    • aggressive
    • large cells and extranodal AND nodal sites
    • treatment= aggressive chemo to include immunotherapy
33
Q

Describe T/NK cell lymphomas

A
  • relatively uncommon in the US
  • aggressive tumors (generally)
  • types
    • peripheral T cell lymphoma
    • anaplastic T cell lymphoma, ALK +
    • extranodal NK/T cell lymphoma
34
Q

Contrast anaplastic T cell lymphoma and extranodal NK/T cell lymphoma

A
  • anaplastic T cell lymphoma
    • aggressive pediatric tumor
    • CD4+ T cell neoplasm
    • characterized by ALK rearrangements (tyrosine kinase receptor)… most commonly t(2;5)
  • extranodal NK/T cell lymphoma
    • aggressive adult tumor
    • mostly NK neoplasm (may be T cell)
    • formerly “midline lethal granuloma”
      • nasal mass with necrosis, extensive destruction, and angioinvasion
    • EBV associated, more common in Asia/S America
35
Q

Describe Burkitt lymphoma

A
  • aggressive B cell lymphoma
  • driven by c-myc translocation
  • histology= “starry sky”
36
Q

What are the 4 clinical variants of Burkitt lymphoma?

A
  • sporatic
    • ileocecal mass
    • more common in children
  • endemic (more common in Africa)
    • EBV, breast, jaw, ovary mass
  • immunosuppression-related (after transplant)
    • EBV
  • transformed follicular lymphoma
37
Q

Describe Hodgkin lymphoma

A
  • ~30% of all lymphomas
  • more commonly observed in young adults
  • characterized by:
    • reed sternberg cells
    • contiguous spread
    • lymph node involvement
38
Q

What are reed sternberg cells?

A
  • must be observed to diagnose hodgkin lymphoma
  • B-lineage neoplastic cells
  • morphology
    • large, frequently binucleated
    • large, eosinophilic nucleoli (“owl eyes”)
  • variants possible (e.g. lacunar cells in nodular sclerosis HL)
39
Q

What are the 2 major classifications of hodgkin lymphoma we need to know? How can you differentiate between them?

A
  • classical HL
    • nodular sclerosis HL most common
    • observe reed sternberg cells
  • nodular lymphocyte predominant HL (“nonclassical”)
    • observe “popcorn cells”
40
Q

Contrast nodular sclerosis HL and nodular lymphocyte predominant HL

A
  • nodular sclerosis HL
    • 15-35 yo, M=F
    • mediastinal location
    • CD15/30 +, CD20/45 -
    • lacunar cells, dense sclerosis
    • aggressive
  • nodular lymphocyte predominant HL
    • 30-50 yo, M>F
    • cervical/axillary location
    • CD15/30 -, CD20/45 +
    • popcorn cells, L&H cells
    • more indolent (wait on treatment, relapses common)
41
Q

What do you see in this lymph node biopsy?

A

Metastatic carcinoma (looks glandular)

**remember! even though we talk a lot about lymphoma, metastasis is the most common!!

42
Q

Contrast Hodgkin and non-hodgkin lymphoma

A