Lymph nodes I_Clinical Pathology Boards Review
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Patient is a Japanese 25F who presented with fever, HA, cervical LAD x 3 wks. Biopsy section shown above. Dx?
Kikuchi dz - paracortex & cortex infiltrated by abundant histiocytes, necrosis without neutrophils
LN: What markers are these?
- Left: BCL-6 (nuclear)
- Right: CD10
LN: What markers are these?
- Left: CD21 (follicular dendritic cells)
- Right: BCL-2 (if rx, GC negative, positive in mantle zone B-cells & paracortex T-cells)
LN: What marker is this?
IgD mantle zones
Mediastinal LAD in otherwise asx pt. Sections show follicular hyperplasia with small, regressed GCs. Many follicles each have multiple GCs, broad onion-skinning of mantle zone, hyalinized vessels. HHV-8 is negative. Dx? Which variant is associated with POEMS syndrome and what stain is typically positive? Which has worse prognosis?
Hyaline vascular type castleman's dz; plasma cell variant with systemic manifestations and HHV-8/LANA+; multicentric variant
All of the following produce follicular patterns of benign LN disease except:
A) Kimura disease
C) Sjogren's or rheumatoid arthritis
A - Kimura is an interfollicular pattern
What benign LN diseases cause an interfollicular pattern?
- 1) Viral infections - mono, CMV, post-vaccine, not HIV
- 2) Hypersensitivity rxns
- 3) Kimura dz
This LN is missing lymphocytes and mantle zones. In a 28M w/h/o IV drug use. Dx?
HIV related LAD - get huge confluent GCs, weird shapes, progress to follicular involution, then lymphocyte depletion (small, fibrotic nodes, absence of follicles, increased dendritic cells)
What type of LAD is produced by Sjogren's, syphilis and rheumatoid arthritis?
Follicular hyperplasia with interfollicular and capsular infiltration by plasma cells, capsular & trabecular thickening
Cervical LN in an HIV+ male. Sections show FH, aggregates of epitheloid histiocytes/ill-formed granulomas near or encroaching GCs (top picture) and lots of monocytoid B-cells in sinuses (bottom picture). Serology is confirmatory. Dx?
All of the following benign LN conditions show a sinus pattern except:
B) Infectious mono
C) Hemophagocytic syndrome
D) Whipple dz
E) Dermatopathic lymphadenitis
F) Lymphangiogram effect
B - this is a paracortical/interfollicular pattern
What is dermatopathic lymphadenitis? In what setting is this found? What hematolymphoid malignancy can mimic this?
Paracortical expansion by histiocytes, many pigmented, Langerhans & interdigitating reticular cells also present; in benign & malig skin d/o; mycosis fungoides looks like this but is confluent
Tender cervical LAD and fever in a 20yo Japanese female. Dx? Prognosis? What is also in the DDx?
Kikuchi-Fujimoto dz - paracortex with necrosis (karyorrhectic debris - blue arrow), sheets of histiocytes, some with crescentic C-shaped nuclei (red arrow), plasmacytoid monos, lymphocytes including CD8+ immunoblasts, absent neuts or PCs; good, self-limiting; lupus (numerous PCs), necrotic lymphoma, herpes LAD, Kawasaki
What mycobacteria causes caseating granulomatous cervical LAD?
All of the following cause suppurative granulomata (stellate abscesses-see above) in LNs except
A) Cat scratch/bartonella henselae
C) Lymphogranuloma venereum
D) M. scrofulaceum
D - causes caseating necrotizing, non-suppurative infection
B/l cervical LAD in 16F. Dx? IHC in larger cells?
Rosai-Dorfman with sinus histiocytosis and emperipolesis; S100, CD68, CD14, lysozyme, HLA-DR, and CD31 (weird!)
What diseases can have this finding?
(Hemophagocytic syndrome with RBC internalization & digestion) - *associated with viruses (EBV), X-linked syndrome, erythrophagocytosis, T-cell lymphomas
Vascular, nodular proliferation in a immunodeficient pt. What is your DDx?
Kaposi's sarcoma vs. Bacillary Angiomatosis/Bartonella henselae vs. angiosarcoma vs. pyogenic granuloma (if was in skin) - KS will have atypical spindle cells, slit-like vascular spaces while BA has plump endothelial cells, little atypia
Associated mutations? Which one has a good prognosis?
- (CLL/SLL - pale nodules of prolif centers (pseudofollicles) composed of small Ls, prolymphs, and paraimmunoblasts)
- 1) 13q14- (50%), 2) trisomy 12 (15-20%), 3) 11q-, 4) 14q-, 5) 17p-
- 13q14- has a good prognosis
What is the IHC profile of CLL? What CLL immunophenotypes are unfavorable?
CD19+, dim CD20+, CD23+, CD5+, CD11c+, CD43+; ZAP-70 and CD38 expression = no Ig variable region (IgVH) somatic hypermutation = pre-GC population = unfavorable
What % prolymphs defines CLL/PLL? PLL? What IHC profile is seen in PLL that differs from CLL?
11-55%; >55%; decreased CD5 and CD23, increased CD22, CD20, sIg
All of the following have a worse prognosis in CLL except:
A) Initial lymphocyte count >30k
B) Interstitial marrow infiltration
C) atypical morphology
D) Peripheral lymph doubling time of ≤1/yr
E) Bright CD20, sIg, or CD38 expression
B - diffuse infiltration is a worse prognosis
55M p/w splenomegaly and pancytopenia. Peripheral blood shows medium-sized cells, pale cytoplasm with projections, reniform/oval or bean-shaped nuclei. Pt p/w pancytopenia, particularly neutropenia and monocytopenia. Dx? How do they present in the BM and spleen? Where do they not tend to invade?
Hairy cell - nucleus is 2x size of regular lymph, cytoplasm; BM subtle interstitial infiltrate with reticulin fibrosis → dry tap, blood lakes, some mast cells; spleen shows hairy cells with cleared cytoplasm that look like "fried eggs" localized to red pulp (see above) with red pulp blood lakes (see above), inconspicuous white pulp; LNs
All of the following can mimic HCL except:
A) aplastic anemia
B) Splenic lymphoma with villous lymphocytes (leukemic phase of marginal zone)
C) Prolymphocytic leukemia
D - AML (M3 & M5) can mimic HCL
What is the IHC profile of HCL?
- "The bright one":
- Positive: CD19, CD20, [bright CD11c, CD25, and CD103], Annexin A1, TRAP, DBA.44, BCL-1(dim to mod), sometimes CD2
- Negative: CD43, CD23, CD5, CD10
In addition to HCL, what conditions are TRAP+? DBA.44+?
- TRAP: HCL, PLL, Waldenstrom, mast cell dz, Gaucher dz
- DBA.44: splenic lymphoma w/villous lymphs, mantle cell, DLBCL, minority of FL
HCL can be confused with splenic lymphoma with villous lymphocytes (SLVL). What marker is negative in SLVL but positive in HCL?
Both are CD11c and CD103 positive, but SLVL is CD25-
In flow, where do HCL cells fall on a CD45 v. SS plot?
monocyte gate - can mask monocytopenia
What is the typical WBC in PLL? BM findings? What is the IHC profile and how does it compare to CLL?
>100k/IL; diffuse marrow effacement (rarely involves LN!); CD5-, strong CD11c, bright sIg, bright CD20, CD22, and FMC-7 while CLL is CD5+, dim sIg, dim CD20, FMC-7 neg.
What do the HCL cells show ultrastructurally?
What are features of HCL variant? What is the prognosis?
Leukocytosis, monos present, CD25 or CD103 neg; poor, resistant to tx
Nodular, effaced LN: BCL2+, BCL6+, CD10+. Dx? How do they appear on peripheral smears? What markers are associated with favorable prognosis?
FL - no tingible body macs, attenuated mantle, decreased mitoses; cleaved cells/"butt cells"; GC markers: CD10 and BCL-6
How is follicular lymphoma graded?
- By # large, non-cleaved centroblasts:
- Grade 1: 0-5 per 40x or <25% of neoplastic cells
- Grade 2: 5-15 per 40x or 25-50%
- Grade 3: >15 per 40x or >50%
When is BCL-2 expressed decreased in FL? What genes are involved in the t(14;18)
Grade 3 and Cutaneous FL; BCL2 on chrom 18 with J region of HC on chrom 14
What lymphomas show focal paratrabecular aggregates in the BM?
FL & TCRBCL (type of DLBCL)
When FL is in the LN and BM, how do they present? What method of detection can cover all types of breakpoints in FL?
Discordant, often with high-grade LN and low-grade BM; FISH
All of the following are factors that go into CLL staging based on the Rai and Binet stages except:
A) Lymphomatosis >10k
D) Anemia (<11g/dL)
E) Thrombocytopenia (<100,000/mL)
A - lymphocytosis of >5k, which is a Rai low risk or Binet stage A if <3 lymphoid areas (LAD and HSM Rai intermed risk or Binet stage B if >3 lymphoid areas), anemia & ↓Plts Rai high risk/Binet stage C)
In MCL, what is the disease when it studs the GI? What is the IHC profile? How does it appear in peripheral blood? Mutations involved other than t(11;14)?
Lymphomatous polyposis; CD19+, CD20+, CD5+, CD23-, CD43+, BCL-1+(nuclear), FMC-7+, bright sIg+, CD11c-(CLL positive), more often λ-restricted; irregular nuclear contour with small delicate nucleolus; chromosomes 17, 21, and 8
What method of detection is best for MCL?
FISH - PCR and Southern blot only pick up 50% of rearrangements b/c the breakpoint area (major translocation cluster/MTC region) is far away from the BCL1 gene
What genes are involved in the MCL translocation?
CCND1 (11q13) with JH region of IgH (14q32) with CCND1 stimulating entrance into G1 phase
LN shows proliferation of plasmacytoid & monocytoid (see above) cells with colonization of the follicles. Plasma cells with Dutcher bodies are noted. IHC: CD19+, CD20+, FMC7+, sIg+, CD5-, CD23-, CD10-. Dx? How does it appear in the splenic variant? What additional lab finding is common? What location sometimes shows CD43+?
MZL; HCL-like cells but w/distinct nucleolus; monoclonal gammopathy; MALT
What is a dutcher body? What malignancies have this?
Intranuclear inclusions, which are accumul of Ig within the nucleus; Waldenstrom's/LPL, MZL
What genes are involved in the MZL t(11;18) translocation? Other translocation involved in MZL? What % of MALT has t(11;18)? What MZL types do not have t(11;18)? What type of tx is t(11;18) resistant to?
MALT1-IgH fusion; t(14;18) with IgH-API2 fusion; 25-50%; primary nodal, MALT w/ progression to DLBCL; resistant to Abx so not good to have this translocation in the gut
All of the following are precursor lesions of MZL except:
B) Reidel's thyroiditis
C) Gastric H. pylori
D) Lyme dz in skin
E) C. jejuni in eye
F) Hep C
B - Hashimoto's, not Reidel's, is associated with MZL
T/F: Level of IgM paraprotein isn't important in Waldenstrom's.
Define Waldenstrom's. What are clinical sxs?
Monoclonal gammopathy + LPL BM involvement + IgM paraprotein; cryoglobulinemia, peripheral neuropathy, hyperviscosity
Which of the following lymphomas are associated with EBV (more than 1 may apply):
A) Lymphomatoid granulomatosis
B) Primary Effusion
C) Post-transplant LPD
D) Hepatosplenic lymphoma
E) Burkitt's lymphoma
F) Extranodal NK/T-cell lymphoma
G) Angioimmunoblastic TCL
H) Classical Hodgkin Disease
All except D
"Starry sky appearance." Dx? What are the three types of this lymphoma? Translocation?
Burkitt - med to large cells with 2 to 5 nucleoli, cells have cobblestone appearance, tingible body macs imparting starry sky appearance from tingible body macs, lipid-containing vacuoles; 1) African endemic - jaw mass, EBV, 4-7yo males, malaria, 2) western sporadic - adults, intra-abd esp ICV or breast of lactating women, 30% EBV, 3) Immunodef, nodal
What are the transolcations involved in Burkitt? IHC profile? What protein does C-myc partner with to drive the tumor cells into the cell cycle?
t(8;14) with C-MYC to IgH or t(2;8) with Igκ(2p12) to C-MYC or t(8;22) with Igλ to C-MYC; (GC phenotype) CD19+, CD20+, CD22+, CD10+, BCL6+, c-myc+, BCL2-, TdT-, CD34-, Ki-67 >99%; Max protein
What molecular markers are present in DLBCL?
BCL2 or BCL6 (chrom 3q27) represent 20-30% of DLBCLs, ex. t(3;14 (q27;q32) associated with higher grade subtype
Most common extranodal site for DLBCL?
In primary cutaneous DLBCL, leg type, what population is affected? Histologic features? IHC profile? Prognosis?
Elderly females; immunoblastic or round cell; MUM1+, strong BCL2+, strong BCL6+, FOXP1+, CD10-; poor, aggressive (unlike other types cutaneous DLBCLs)
What type of lymphoma is usually seen in primary CNS lymphoma? Peak age group? Where does it arise?
DLBCL; 60yo (but 35yo for HIV+); supratentorial frontal, temporal, or parietal lobes as solitary lesion
Mediastinal mass in 30F. IHC showed CD20+ B-cells that were CD30+(weak), CD5-, CD10-, MAL protein+, sIg-, molecular studies showed IgH rearrangement. Dx?
Mediastinal (sclerosing) large cell lymphoma - centroblast-like B-cells with clear cytoplasm (fried eggs) obscured by bands of sclerosis
What is lymphomatoid granulomatosis and where does it present? What virus is associated? What other lymphoma is in the DDx?
Angiocentric & angiodestructive B-cell process resembling vasculitis, granulomas uncommon; in extranodal sites like lung as one or multiple tumors but can be found in upper aerodigestive, brain, kidneys, liver; EBV; T/NK-cell angiocentric lymphoma
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