9a- Lymphadenopathy Flashcards
Describe the transit of B cells into and out of the lymph node
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
Describe the transit of T cells into and out of the lymph node
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
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?
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
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?
Indicative of neoplasm (cellular atypia and no secondary follicles)
- extensive, marked lymphadenopathy
- drenching night sweats
- monoclonal B/T cells
Describe the duration, size, location, tenderness, mobility and consistency of a benign lymphadenopathy
- duration= < 2 weeks
- size= < 2 cm (1 cm= normal)
- location= cervical, inguinal
- tenderness= tender
- mobility= mobile
- consistency= soft
Describe the duration, size, location, tenderness, mobility and consistency of a malignant lymphadenopathy
- duration= > 2 weeks
- size= > 2 cm (1 cm= normal)
- location= supraclavicular
- tenderness= non-tender
- mobility= fixed
- consistency= firm, hard
Describe the architecture, dominant cell type, atypia, and ancillary study (flow cytometry) findings of benign lymphadenopathy
- architecture= intact
- dominant cell type= small lymphs
- atypia= none
- ancillary study findings= polyclonal
Describe the architecture, dominant cell type, atypia, and ancillary study (flow cytometry) findings of malignant lymphadenopathy
- architecture= effaced
- dominant cell type= large lymphs/epithelial cells
- atypia= present
- ancillary study findings= monoclonal
What are B symptoms? What do they usually represent and how are they used?
- 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)
What are some causes of reactive lymphadenopathy?
- infectious
- autoimmune
- drugs
- foreign body (e.g. orthopedic surgery)
- Castleman’s disease
- Sarcoidosis
- Kikushi-Fujimoto
- Kimura’s disease
- Rosai disease
What are some causes of neoplastic lymphadenopathy?
- lymphoma
- leukemic involvement
- lymphoblastic lymphoma
- myeloid sarcoma
- metastatic tumor (most common!)
What are 6 histologic patterns of reactive lymphadenopathy (and what disease processes cause them)?
- 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
What does this image show?
Follicular hyperplasia
What does this image show?
Paracortical hyperplasia
What does this image show?
Sinus histiocytosis
What does this image show?
Granulomatous inflammation
What are two major differentials to consider if you saw this biopsy image?
- follicular lymphoma (more likely due to crowding)
- follicular hyperplasia (benign; less likely)
What is a common treatment plan for follicular lymphoma?
- 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
Describe follicular lymphoma; what is its prevalence?
- 60 yo median age, slight male predominance
- nodal > extranodal
- extensive, generalized adenopathy
- 20% of all lymphomas; 1/3 of B cell lymphomas
What is the genetic variation that common causes follicular lymphoma?
Most characterized by t(14;18)
What is the disease progression of follicular lymphoma?
- generally indolent
- 40% transform to aggressive lymphomas
- diffuse large B cell lymphoma
- Burkitt lymphoma
What does this image show?
- “starry sky” appearance of Burkitt lymphoma
- increased cellularity= “sky”
- lighter macrophages= “stars”
What are the B cell non-hodgkin lymphomas (NHLs) we need to know (6)?
- follicular lymphoma
- diffuse large B cell lymphoma
- mantle cell lymphoma
- marginal zone lymphoma
- lymphoplasmacytic lymphoma
- Burkitt lymphoma
What are the morphologies that help differentiate the B cell NHLs?
- nodular, follicular
- follicular lymphoma
- mantle cell lymphoma
- marginal zone lymphoma
- CLL/SLL
- diffuse
- diffuse large B cell lymphoma
- Burkitt lymphoma
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
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)
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
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
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
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
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
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
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
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
Describe Burkitt lymphoma
- aggressive B cell lymphoma
- driven by c-myc translocation
- histology= “starry sky”
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
Describe Hodgkin lymphoma
- ~30% of all lymphomas
- more commonly observed in young adults
- characterized by:
- reed sternberg cells
- contiguous spread
- lymph node involvement
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)
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”
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)
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!!
Contrast Hodgkin and non-hodgkin lymphoma
