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
What are the tumor sizes that help differentiate the B cell NHLs?
* 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
What are the immunophenotypes that help differentiate the B cell NHLs?
* 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
What are the cytogenetics that help differentiate the B cell NHLs?
* 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
Describe the cellular result of the t(14;18) translocation
* 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
Describe the cellular result of the t(11;14) translocation
* cyclin D1 - IgH fusion * cyclin D1 overexpressed, allowing increased cell growth \*\*diagnosis for mantle cell lymphoma
30
Describe the cellular result of the t(8;14) translocation
* c-MYC - IgH fusion * c-MYC= oncogene * results in agressive proliferation when translocated next to IgH \*\*diagnosis for Burkitt lymphoma
31
How would you grade the B cell NHLs? (low, medium, high)
* low * CLL/SLL * follicular lymphoma * marginal zone lymphoma * lymphoplasmacytic lymphoma * medium * mantle cell lymphoma * high * diffuse large B cell lymphoma * Burkitt lymphoma
32
Contrast extranodal marginal zone lymphoma and diffuse large B cell lymphoma
* 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
Describe T/NK cell lymphomas
* relatively uncommon in the US * aggressive tumors (generally) * types * peripheral T cell lymphoma * anaplastic T cell lymphoma, ALK + * extranodal NK/T cell lymphoma
34
Contrast anaplastic T cell lymphoma and extranodal NK/T cell lymphoma
* 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
Describe Burkitt lymphoma
* aggressive B cell lymphoma * driven by c-myc translocation * histology= "starry sky"
36
What are the 4 clinical variants of Burkitt lymphoma?
* 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
Describe Hodgkin lymphoma
* ~30% of all lymphomas * more commonly observed in young adults * characterized by: * reed sternberg cells * contiguous spread * lymph node involvement
38
What are reed sternberg cells?
* 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
What are the 2 major classifications of hodgkin lymphoma we need to know? How can you differentiate between them?
* classical HL * nodular sclerosis HL most common * observe reed sternberg cells * nodular lymphocyte predominant HL ("nonclassical") * observe "popcorn cells"
40
Contrast nodular sclerosis HL and nodular lymphocyte predominant HL
* 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
What do you see in this lymph node biopsy?
Metastatic carcinoma (looks glandular) \*\*remember! even though we talk a lot about lymphoma, metastasis is the most common!!
42
Contrast Hodgkin and non-hodgkin lymphoma