1
Q
Name some clinical, morphological, immunohistochemial features, cytogenetics of anaplastic large cell lymphoma?
A
- 2 subgroups; ALK+ and ALK-
- ALK+ usually presents in young adults, skin/soft tissue, good prognosis
- ALK- usually presents in older individuals, more aggressive, worse prognosis
- Cohesive proliferation of neoplastic T/null cell phenotype, subcapsular in nodal
- Hallmark cells: polylobated wreath like nuclei within large cells with multiple nucleoli
- background of prominent mixed inflammatory cells
- multiple morphologic variants incudling classic/small cell/sarcomatoid etc.
- IHC CD30+, EMA+, CD25+ with variable CD2/3/4/TIA1/granzyme B/perforin
- ALK-1 positive in subset with t (2;5) ALK-NPMN1 but other translocation partners
2
Q
T-cell lymphoblastic leukemia/lymphoma presents as a mediastinal mass. What is the ddx?
A
- Thymic lesions: hyperplastic thymus, thymoma, thymic carcinoma
- hodgkin lymphoma
- germ cell tumor
- metastasis
3
Q
What is the cell of origin of T-cell angioimmunoblatic Tcell lymphoma. What are the clinical and morphologic features of this neoplasm?
A
- Putative cell of origin: follicular T-cell
- Clinical: fever, weight loss, skin rash, polyclonal hypergammaglobulinemia (can have clonal B-cell changes too)
- autoimmune hemolytic anemia
- increased susceptibility to infections/immunosuppression
- diffuse lymphadenopathy
- morphology: effaced nodal architecture, pleomorphic background of lymphocytes, plasma cells, eos, immunobasts
- sparing of subcapsular sinuses
- prominent vascularity with arborizing vessels
- extrafollicular proliferation of CD21/23 positive follicular dendritic cells
- scattered neoplastic T cells with clear cytoplasm, expressing C3/CD4/BCL6/CXCL13
- 2nd population of CD20+immunoblasts
- Usually EBER+
- cytogenetics: trisomy 3,5,X
*** possible monoclonal rearrangement of both TCR and IGH receptor genes
4
Q
List 4 types of primary extranodal T/NK neoplasms
A
- Extranodal NK/T-cell lymphoma, T-cell type
- Enteropathy associated T-cell lymphoma
- Hepatosplenic T-cell lymphoma
- Subcutaneous panniculitis-like T-cell lymphoma
- Primary cutaneous T-cell neoplasms:
Mycosis fungoideds/Sezary syndrome
- Primary cutaneous CD30+ lymphoproliferative disorders
- ALCL (primary cutaneous)
5
Q
Compare and contrast Classic hodgkins and NLPHL
A
CHL
morphology: macronodules, fibrou bands, pleomorphic background of lymphos,eos, histiocytes. Mononucleate/binucleate Reed-Sternbergs with conspicuous nuclei.
IHC: CD30/CD15/PAX5/MUM1 POSITIVE. EBER more likely to be positive.
CD20/OCT2/BOB1/CD45 NEGATIVE
IGH/TCR neg
NLPHL:
Morphology: macronodules without fibrosis, more monotonous background of small lymphs. Polylobated LPs with inconspicuous nuclei and wreats of CD57+ lymphs.
IHC: CD45/CD20/PAX5/MUM1, EMA, OCT2, BOB1
CD15/CD30/CD3/EBER NEGATIVE
IGH: may be rearranged
6
Q
Classify Hodgkins lymphoma
A
Nodular lymphocyte predominant
Classic
- nodular sclerosing
- lymphocyte rich
- lymphocyte depleted
- mixed cellularity
7
Q
List 5 factors contributing to renal insufficiency in plasma cell myeloma
A
- Hypercalcemia
- Hyperuricemia
- Hyperviscosity
- Recurrent bacterial infections/pyelonephritis
- Proteinuria (Bence-Jones light chain nephrotoxicity)
- AL amyloidosis
- Extramedullary plasma cell infiltrates
- Contrast/radiographic studies
8
Q
What are the diagnostic criteria for symptomatic plasma cell myeloma?
A
- M protein in serum/urine
- BM clonal plasmacytosis/plasmacytoma
- Organ or tissue impairment (eg. renal function, fever, weight loss etc.)
9
Q
List 5 distinct clinicopathologic plasma cell disorders
A
- Plasma cell myeloma (multiple myeloma) including asymptomatic myeloma, non-secretory myeloma, plasma cell leukemia
- Plasmacytoma including solitary plasmacytoma, extraosseus plasmacytoma
- Osteosclerotic myeloma (POEMS-polyneuropathy, organomegally, endocrine disturbance, M protein, skin changes)
- Monoclonal gammopathy of uncertain significance
- Immunoglobulin deposition disease (primary amyloidosis, systmeic light/heavy chain deposition disease)
- Heavy chain diseases: Gamma-HCD, alpha-HCD, Mu0HCD, Waldenstroms macroglobulinemia
10
Q
B-cell lymphomas: list some translocations/cytogenetic alterations that can be detected by FISH
A
- Follicular lymphoma t (14;18) BCL2-IGH
- 17p deletions/mutations-p53 gene
- Additional BCL6, MYC gene abberations
- MALT t(11;18) API2/MALT associated with resistance to H.pylori eradication therapy
- Splenic marginal zone (loss of 7q, dysregulation of CDK6 gene)
- Diffuse large B cell (t 14:18, BCL6 or CMYC)
- Burkitt t (8;14), (2;8) or (8:22) fusion genes of C-MYC with IGH etc.
- Mantle cell lymphoma (11;14) Cyclin D1/IGH
11
Q
How does BCL6 figure into the pathogenesis of DLBCL?
A
- Acquired aberrations of BCL-6 gene may be compounded by additional cytogenetic abberations (including BCL2, C-MYC)
- Overexpression of BCL-6 protein results in anti-p53 actiity and disruption of DNA repair mcehanisms
- Overexpression of BCL-6 represses factors promoting germinal centre differentiation
- BCL6 locus is on chromosome 3 (DNA binding zinc-finger transcription repressor)
12
Q
List some subtypes of DLBCL
A
- Primary mediastinal DLBCL
- Primary effusion lymphoma
- Primary cutaenous DLBCL
- Intravascular DLBCL
- T-cell rich B-cell lymphoma
- Primary CNS DLBCL
- Primary cutaneous DLBCL, leg type
- EBV positive DLBCL of the elderly
- DLBCL from chronic inflammation
- ALK+ DLBCL
- Plasmablastic lymphoma
HHV-8 associated large B-cell lymphoma from multicentric Castleman’s
13
Q
What are negative prognostic factors in follicular lymphoma?
A
- presence of diffuse areas of centroblasts (grade 3b)
- Blastic cytomorphology with high ki67
- Additional cytogenetic abnormalities (in addition to t 14;18) including p53 inactivation, activation of C-MYC/BCL-6 genes
- loss of BCL-6 protein and acquisition of MUM-1 expression
14
Q
List architectural patterns of chronic non-specific lymphadenopathy & clinicopathological associations
A
- Follicular pattern: RA, SLE, toxoplasmosis, early HIV, also in LN draining any infection
- Sinus pattern: sinus histiocytosis w/massive lymphadenopathy (Rosai-Dorfman), local drainage from malignancies
- Paracortical hyperplasia: dermatopathic lymphadenopathy, infectious mononucleosis, other viral
- Mixed: chronic/late HIV infection
15
Q
What are important diagnostic features of syphilis lymphadenitis?
A
Extensive follicular hyperplasia
Lymphoplasmacytic periarteritis
Epithelioid granulomas and rare giant cells
thickened capsule
prominent vessel in interfollicular areas
extensive plasmacytosis in interfollicular areas
Spirochetes (treponema pallidum) can be seen with Warthin Starry Stain
PCR+ for t. pallidum
16
Q
Compare and contrast reactive follicles with follicular lymphoma
A
Reactive: variable shapes, located in cortex, preserved interfollicular area, variably sized germinal centers with tingible body macrophages and mitoses, mantle zones sharply demarcated, polarized (dark and light zone). They are BCL2 neg, but positive for CD10, BCL6, CD21/23 highlight intact meshwork and ki67 is elevated. B-cell IGH receptor is polyclonal and BCL2 gene is intact.
FL: fused/crowded germinal centers in all compartments effacing interfollicular area, monomorphic germinal centers lacking tingible body macrophages with only rare mitoses and absent mantle zone. No polarity. IHC: BCL2+, CD10+, BCL6+, distorted meshwork by CD21/23, low ki67. Monoclonal IGH receptor and BCL2 gene rearragnements.
17
Q
What are the clinicopathologic variants of Castleman’s and what are the salient features?
A
Both are forms of lymphoid hyperplasia
Hyaline vascular variant (unicentric)
**- **atrophic appearing and lymphocyte depleted germinal centers with hyaline deposits at centre
- mantle cell hyperplasia with concentric layers forming onion-skin lesions
- prominent interfollicular vascularity, with vessels penetrating germinal centers forming lollipop lesions
- lymphocytes mainly CD21/CD23/CD35 folliciular dendritic cells
Plasma cell variant (unicentric, multicentric)
Follicular hyperplasia with large germinal centers
Diffuse plasma cells between follicles, often with Russell bodies
No hyaline-vascular changes present
Center of follicle has amorphic eosinophilic material (fibrin, immune complexes)
HHV8 related, plasmablastic variant
18
Q
What are the morphologic features diagnostic of progressive transformation of germinal centers?
A
- Retained nodal architecture with follicular hyperplasia
- Well-demarcated macronodular structures
- Intact interfollicular areas
- Poorly defined mantle zones with progressive fusion and infiltration of germinal centres by IGM/IGD positive mantle zone B cells
- Collectoins of epithelioid histiocytes surrounding PTC macronodules
- Lack of LP cells of NLPHL
19
Q
What’s emperiopolesis and what are the morphologic features of Rosai-Dorfman?
A
Emperiopolesis: process of engulfment of viable/intact cells into intracytoplasmic vacuoles by macrophage cells;
Rosai Dorfman: nodla enlargement/extranodal mass
exbuerant expansion of sinuses
Sinuses filled with S100/CD68/CD4 positive histiocytes lacking Cd1a or langerin
Emperiopolesis
Polyclonal plasmacytosis in the medulla
Some association with IgG4
20
Q
Name 3 clinical conditions that may result in impaired immunodeficiency
A
- Congenital immunodeficiency disorders (severe combined immunodeficiency, x-linked agammaglobulinemia…)
- Chronic viral infections, HIV/HTLV/HHV8
- Iatrogenic/immunosuppressive therapy: post-BMT/solid organ/malignancy; chemotherapy, steroids, cyclosporine, azathioprine, radiation
- Autoimmune disorders: Sjogren, Hashimoto, UC, Crohns
21
Q
What 3 patterns of HIV lymphadenitis are there? What does the typical acute pattern show?
A
Acute, chronic, burned out
acute phase: florid follicular hyperplasia, expanded large and irregularly (dumbbell) shaped germinal centers, attenduated mantle zones giving appearance of naked germinal centeres and follculolysis, aggregates of plasma cells, macrophages, monocytoid B cells, immunoblasts in interfollicular areas with Warthen-Finkeldey multinucleate igiant cells, possible neutrophil infiltration in sinuses
22
Q
What does acute lymphadentis with EB look like?
A
Paracortex expapnded by heterogenous population of immunoblasts, centroblasts, plasmablasts
Immunoblastic rxn that can be florid, giving moth-eaten look
Numerous CD30+ immunoblasts
Backround of CD3/CD8+ cytotoxic Ts
EBV+ by EBER (ish) or IHC for EBV LMP1
Positive monospot test
germline configuration of IgG/TCR
23
Q
What human viruses of the Herpesviridae family, other than EBV, can cause distintive lymph node patterns?
A
Human herpes virus (HSV1, HSV2) can give herpes lymphadenitis
Varicella herpes zoster (HHV3)
CMV (HHV5) giving CMV lymphadenitis
HHV8, giivng Castleman lymphadenopathy, plasma cell variant
24
Q
Toxoplasmosis: give 2 clinical and 3 histologic featurs
A
- Usually solitary cervical lymphadenopathy, often young women
- Protozoan Toxoplasma gondii (from cat shit)
- HISTO: background of follicular hyperplasia, collections of epithelioid histiocytes encroaching on reactive germinal centres, monocytoid B-cell hyperplasia in subcapsular/trabecular sinuses
25
Dermatopathic lymphadenitis. What are morphological and IHC features of this specific lymph node reaction pattern?
Common in lymph nodes draining areas of cutaenous inflammation/underlying skin disease
Macronodules in paracortical T-zone
Mottled appearance, with pleomorphic infiltrate of:
- S100 dendritic cells CD1a+ Langerhans cels, C68+ hemosiderophages/ or melanophages
26
What are some common symptoms affecting pts with Kikuchi lymphadenitis?
Cervical lymphadenopathy, fever, leukopenia, skin rash
27
What is the morphologic ddx of syphilis related lymphadenitis?
Tuberculous lymphadenitis
Rheumatoid arthritic lymphadenitis
Polyarteritis nodosa
Sarcoidosis
Follicular lymphoma
IgG4
28
List some clinical features associated with multicentric plasma cell variant of Castlemans
B symptoms (fever, weight loss, night sweats), hepatosplenomegally, cytopenias, polyclonal hypergammaglobulinemia, increased LDH, ESR, CRP, IL-6, increased susceptibility to infections, association with POEMS, association with HIV, HHV8
29
Rheumatoid arthritis may be associated with which clinical findings?
- cytopenias, monoclonal paraprotein, amyloid, increased risk of B-cell neoplasm (de novo or therapy induced), splenomegally, clonal proliferation of T-NK cells, lymphadenoapthy
30
What are some morphologic features of rheumatoid arthritis related lymphadenopathy?
- extensive follicular hyperplasia of cortex/medulla
Prominent germinal centers
intense interfollicular plasmacytosis, some russell bodies
Distended sinuses filled with neutorphils
small areas of necrosis
31
What are some pathogenic factors associated with Castleman's?
- HHV8, HIV
- IL-6/VEGF overexpression
32
List the types of Castlemans
Hyaline vascular variant
Plasma cell variant (unicentric, multicentric)
Mixed
33
What conditions are associated with progressive transformation of germinal centers?
- Follicular hyperplasia
Congenital immunodeficiency disorders, such as autoimmune lymphoproliferative syndrome
Hodgkin lymphoma (NLPHL)
34
What should be kept in the ddx of dermatopathic lymphadenitis?
- Nodal involvement by mycosis fungoides
- Interfollicular classic hodgkins
- peripheral T-cell lymphoma
- Malignant histiocytosis
-
35
List some HIV associated lymphoproliferative disorders. What is the overall risk compared to immunocompetant individuals?
- 60-100x general risk
- HHV8+ Castlemans
- DLBCL
- PEL
- Primary CNS lymphoma
- Oral palsmablastic ALK+ B cell lymphoma
36
Name some agents that can present with suppurative granulomas in lymph nodes
- Mycobacterium tuberculosis
- Chlamydia trachomatis (lymphogranuloma venereum)
- Francisella tularensis (tularemia)
- Yersinia pseudotuberculosis (mesenteric lymphadenitis)
- Listeria monocytogenes (listeriosis)
37
List 3 conditions where you may see emperiopolesis
- Sinus histiocytosis with massive lymphadenopathy (rosai dorfman)
- Hemophagocytic syndrome
- Macrophage activation syndrome
38
Name 5 markers present on imamture stem cells/progenitor lymphoid blasts
- CD45
- TDT
- CD34
- CD1a
- CD10
- cytoplasmic mu heavy chain
39
B-ALL is most common type of acute leukemia in kids. What clinical/cytogenetic factors adversely affect prognosis in children?
- Age \<2 and \>10 years
- WBC \>100 000 at presentation
- MLL gene aberrations
- BCR-ABL translocation (9;22)
- minimal residual disease detection following induction chemotherapy
40
What are predictors of unfavourable outcome in CLL?
- Pre-germinal center B-cell phenotype (unmutated IgHV genes)
- Expression of ZAP70
- Expression of CD38
- Atypical convoluated cell morphology
- Presence of cytogenetic aberrations, such as deletion of 11q22 (ATM) or 17p13 (p53)
- diffuse pattern of bone marrow involvement
- marked expansion of proliferation centers and high proliferation index
- increase in circulating prolymphocytes
41
CLL can undergo Richter's transformations to what types?
- Prolymphocytic transformation with increased circulating prolymphocytes or tissue paraimmunoblasts
- DLBCL
- Blastic transformation
- Classic Hodgkins
42
What is the morphologic hallmark/tumor pathogenesis of mantle cell lymphoma?
- Presence of 11;14 translocation, moving cyclin D1 to IGH
- overexpression of cyclin D1 with upregulation of Cyclin D1 coounteracting effects of tumor suppressor genes such as RB and p27
- CYclin D1 dysregulation promoting G1--\>S phase progression and disruption of normal cell cycle
43
What morphologic/IHC features define mantle cell lymphoma?
- Vaguely nodular, monotonous proliferation of centrocyte-like cells
- perivascular sclerosis, scattered pink histiocytes
- frequent mitoses
- Coexpression of CD5/BCL2/Cyclin D1
44
List 5 reactive/inflammatory/autoimmune conditions associated with MALT
- Hashimoto thyroiditis
- Sjogren syndrome
- Lymphoepithelial/myoepithelial sialedenitis
- Follicular gastritis
- Follicular bronchiolitis
45
Other than centroblastic DLBCL morphology, what are some other morphologies?
Plasmablastic, anaplastic, immunoblastic
46
What is the IHC profile of a renegade malignant plasma cell
CD138/CD38/EMA/MUM1 positive
MAY show cyclin D1 positive (poor prognostic)
Monotypic Ig light chain restriction
absence of CD45/CD20/CD3 expression
usually CD56 positive but is variable
47
CD30 is a non-specific activation marker. Where is it expressed?
- Anaplastic large cell lymphoma (both ALK+ and ALK-)
- Classic Hodgkins
- Primary mediastinal B-cell lymphoma
- EBV positive DLBCL of elderly
- EBV+ lymphoproliferative disorders of childhood
- Postransplant lymphoproliferative disorders
- primary cutaenous CD30+ lymphoproliferative disorders
- Large cell transformation in mycosis fungoides
48
Describe Kikuchi lymphadenitis
- Self-limited and spontaneously regressing granulomatous/histiocytic necrotizing lymphadenitis affecting young women
49
What are the morphologic features of Kikuchis?
- Morphologic changes similar to SLE
- Patchy areas of paracortical necrosis with karryorectic debris, but no neutrophils
- Aggregates of MPO+/CD68+/lysosyme+ histiocytes with crescentic nuclei
- paracortical expansion by CD8+ t lymphocytes/immunoblasts
- rare CD20+ lymphocytes
increased # of CD68/CD4/CD123/CD4/CD3 plasmacytoid dendritic cells
50
What are the morphologic features of cat scratch disease and what is the causative organism?
- Bartonella henselae
- Follicular hyperplasia with monocytoid B cell rxn
- Stellate microabcesses/granulomas surrounded by palisading macrophages, forming suppurative/caseating granulomaous lesions
- areas of necrosis with neutrophils
Use warthin-starry to see b. henselae in vessel walls/areas of necrosis
51
What are the genetic abnormalities and pathogenesis of autoimmune lymphoproliferative syndrome?
- Genetics: Autosomal dominant, immune regulation immunodeficiency disorder
- variable genotype/penetrance, resulting in variable onset from birth to late teens with variable severity
- three mutations: FAS gene (CD95), FASLigand (CD178), caspases 8/10
- pathogenesis: impairment of FAS/FASligand mediated cell death/apoptosis
52
What are the clinical and morphologic features of ALPS?
- CLinical: generalized lymphadenopathy, splenomegally, hypergammaglobulinemia, autoimmune cytopenias, bacterial infections, increased risk of lymphoma development
- Morphology: paracortical hyperplasia, florid follicular hyperplasia, prsence of progressive transformation of germinal centers, polyclonal plasmacytosis, massive sinus histiocytosis, increased fraction of polymorphous CD5+ B cells
- Expansion of cirulcating CD45/HLA-DR+ CD3/TCR a/b T cells lacking CD4/8 expression (double negative cells) but with cytotoxic antigens (perforin/TIA/CD57)
53
List B cell markers/plasma cell markers
- Pax 5, CD79a, CD20, kappa, lambda
- CD138, MUM1, EMA, cyclin D1
54
List most common T cell markers
- CD3, CD1a, CD2, CD5, CD4, CD8, CD7, CD43
55
List markers that can be used to subclassify mature T/NK cell neoplasms
- CD1a, CD2, CD3, CD4, CD5, CD7, CD8
- CD10, CD30
- TCR a/b, TCR g/d
- granzyme B, perforin, TIA1
- ALK1
- EBER
56
Give a short description of how flow cytometry is performed
For immunophenotyping, viable and unfixed cell suspensions are stained against various CD cellular antigens with fluorescent markers; these are conjugated to fluorochromes then washed
- the cell bearing the antigen binds the fluorochromej conjugated antibody
- the cell suspension is passed through a flow cytometer one cell at a time; a laser excites the fluorochromes and a light with a particular wavelength is emitted; this is captured by cytometer detectors
- the light is converted to electrical signals, which are depicted as cell plots/histograms in varous colours
- the histograms are evaluated by pathologists to construct cell phenotype by pattern analysis
- gating refers to subset extraction (i.e. limiting the plot to certain signals)
57
flow cytometry plot of normal; forward scatter and side scatter. Granulocytes have more side scatter. Erythrocytes have less forward scatter. Blasts are near the middle. Lymphocytes are at the front. Monos are between the grans and lymphs.
see quesitons
58
Describe in brief the IHC procedure
- Uses fixed (neutral ph 7 buffered formalin) paraffin embedded tissue sections
- Heat induced antigen retrieval to enhance detection
- Cellular antigen of interest, primary antibody targeting antigen, detection system to visualize antigen-antibody complex
- resulting section is interpreted visually, although image analysis software can be used
59
Name 3 tests, other than IHC, used in lymphomas.
Molecular cytogenetics: FISH: C-myc, BCR-ABL, FLT-3
PCR: IgH/TCR/BCL2/JAK2
ISH: EBER
60
What are the cytology features suggestive of lymphoma on FNA?
- Abundant discohesive diagnostic cells
- Scant cytoplasm, conspicuous nucleoli
- Coarsely clumped chromatin with distinct nulear membrane
- Note: High-grade/large cell lymphoid neoplasms can be suggested on FNA but not reliable for small cell neoplasms
61
Give the basic classification of lymphoid neoplasms
- Precursor B- cell neoplasms
- Precursor T-cell neoplasms
- Mature B cell lymphomas/plasma cell neoplasms
- Mature NK and T cell
- Hodgkin (B-cell of altered germinal center B cells), in classic form incapable of Ig transcription
62
What are some cytogenetic criteria in B-ALL indicating good, intermeiate, poor prognosis
Good:
* hyperdiploidy (53-59 chromosomes), trisomies (4, 10, 17), t (12;21)
Intermediate:
* hyperdiploidy, but closer to diploidy
* t (1;19)
Poor:
* near triploidy/tetraploidy
* prensence of MLL gene aberrations (ch11)
* deletion 9p
* postremission additional clonal aberrations
63
What clinical features in a low-grade B cell neoplasm may indicate transformation to a higher grade?
- Marked increase in LDH
- Sudden increase in lymphadenopathy/splenomegally
- Markedly worsening cytopenias or transfusion requirmnets
- new/rapidly enlarging lymph nodes
64
Compare the CD5+ B cell neoplasms (CLL, MCL, HCL)
CLL: indolent, increased incidence with age, associated with persistent lymphocytosis/splenomegally/lymphadenopathy, bone marrow involvement common. monomorphous infiltrate of small lymphocytes. C20/CD5/BCL2+. CD23/43 variable. BCL6/TRAP negative. Cyclin D1 neg. Del 13q, Trisomy 12.
MCL: aggressive, has lymphadenopathy/splenomegally/lymphadenopathy +/- BM involvement. Centrocyte like infiltrates of peripheral blood/bone marrow. CD20+/CD5+/BCL2+ negative for 23/43. BCL6/MUM1/TRAP neg. CYCLIN D1+. t (11;14).
HCL: indolent/curable. Spleno/lymphocytosis/BM INVOLVMENT ALWAYS. SMall lymphocytes, bean shaped nuclei, abundant cytoplasm with hairy projections. CD20/CD11c/CD103/CD25/DBA44/TRAP
CD5 negative, cyclin D1 negative
65
MCL: give some clinical features and poor morphologic prognosticators
- Clinically aggressive B-cel neoplasms
- Commonly involves gut (lymphomatous polyposis), spleen, Waldeyer ring, lymph nodes, bone marrow
- intermediate sized cells, monomorphic
- poor prog: blastic/pleomorphic variants, enhanced ki67
66
What other malignancies can have cyclin-D1 expression?
- Plasma cell neoplasms
- Splenic marginal zone lymphoma
- B-cell prolymphocytic leukemia
67
Name some site specific MALT formations and their role
- specialized mucosa associated lymphoid tissue protects permeable mucosal surfaces from external pathogens
- Gut associated peyer's patches, weldeyer ring, vermiform appendix
68
Name some organisms associated with MALTomas
Skin; Borrelia burgdorferi
Gastric: h. pylori
Ocular adnexal malt: Chlamydia psittaci
immunoproliferative small intestinal disease: campylobacter jejuni
69
What is immunoproliferative small intestinal disease?
- occurs in middle east/south africa
- young adults
- severe malabsorption
- responds to abx, since campylobacter jejuni is implicated
- for of MALT with prominent plasmacytoid differentiation
- associated with truncated alpha heavy chains
70
Name some hematolymphoid neoplasms involving the spleen
- Splenic marginal zone lymphoma
- Hairy cell leukemia
- Mantle cell lymphoma
- Splenic diffuse red pulp small B lymphoma
- CML
- also follicular lymphoma
71
Splenic marginal zone lymphoma: differentiate from MALT
- exclusively involves spleen, BM, peripheral blood
- intrasinusoidal infiltrates in BM
- associated with HepC
- serum monoclonal paraprotein
- chromosome 7q21 deletion in 40% (NO 14;18)
- greater frequency of transformation to HG lymphoma
- can be cured by splenectomy
72
Describe some MALT features
- Monocytoid/lymphoplasmacytoid features
- Residual reactive follicles with mantle zones distorted by colonization and distorted meshwork of CD21/23 follicular dendritic
- CD5/CD10/Cyclin D1 NEGATIVE
- CD20/CD43 positive
- trisomy 3, 7, 12, 18 common
73
Follicular lyphoma: molecular hallmarks
- most common indolent B cell lymphoma in NA/Europe
- t (14;18) is present in 90%
- puts IgH gene nexto BCL2, leads to overexpression of BCL2
- BCL2 disrupts apoptosis pathway;leads to neoplastic transformation but mostly just cells refusing to die
- Ongoing mutations (MYC, BCL6) lead to more aggressive grade/DLBCL
-
74
Describe the morphologic features of centroblast/centrocyte and describe grading of FL
Centrocyte: small cleaved lymphoid cell, indiscernable nucleloi, scant cytoplasm
Centroblast: large, nucleus 2x normal endothelial cell, large non cleaved with vesicular chromatin, few inconspicuous nucleoli, basophilic cytoplasm
grading: Either 3-tier or 2
Gr1: 0-5 centroblasts/HPF, Gr2: 6-15, Gr3: \>15
3a=mix of centrocytes/blasts, 3b=diffuse sheets of centroblasts, treated like DLBCL
75
Burkitt: what are clinical subtypes, give features of endemic
-Endemic, Sporadic, HIV associated
Endemic: kids, subsaharan Africa, rapidly enlarging mass in mandible/kidneys/ovaries/adrenals/HandN
8;14, 8;22 or 2;8
C-MYC on 8 next to IG promoter on chromosome 14, leading to c-myc overexpresssion alternatively next to heavy chain or light chain
C-MYC autonomously dividing/always in cell cycle, not differentiating
Nearly all endemic Burkitts have EBV DNA
76
DLBCL - clinical, morphology, IHC, molecular
- usually older, nodal mass, de novo/or from follicular, usually not EBV unless elderly, multiple clinical variants
- diffuse proliferation of centroblasts
- CD20+ with variable CD10/BCL2/BCL6/ki67
- BCL6 rearrangement in 70%, BCL2 in 30%, CMYC in 8%
77
What are the features of B cell lymphoma, intermediate between DLBCL and BL?
Any age, nodal/extranodal/aggressive
Intermediate sized blasts with irregular nuclear contours, inconspicuous nuclei but starry sky and freqent mitoses
IHC: CD20+, CD10+, BCL6+ +/- BCL2 with high ki67
have CMYC in 50%, BCL2 in 15%, BCL6 in 10%
78
BL: what are the IHC
- CD20/CD10/BCL6/Ki67 (almost 100%)
- BCL2 neg.
79
Hemepath & spleen
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