Lymph Nodes 1 Flashcards
Bcl-6
Follicular centers - nuclear
CD10
Follicular centers - cytopasmic
CD21
Follicular dendritic cell network
IgD
follicular mantle zone
Patterns of benign lymphadopathy - Follicular
– Follicular Hyperplasia
– Giant lymph node hyperplasia-hyaline vascular (Castleman disease)
– Progressively transformed germinal centers
– HIV-related lymphadenopathy
– Rheumatoid lymphadenopathy
– Syphilitic lymphadenopathy
Patterns of benign lymphadopathy - Paracortical
– Viral infections, NOS – Post-vaccinial lymphadenitis – Infectious mononucleosis (Epstein-Barr virus) – Drug induced hypersensitivity – Angioimmunoblastic lymphadenopathy – Dermatopathic lymphadenitis – Histiocytic necrotizing lymphadenitis (K-F disease) – Systemic lupus erythematosus
Patterns of benign lymphadopathy - Sinus Pattern
– Sinus histiocytosis – Langerhans cell histiocytosis (EG, H-X)? – Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) – Monocytoid B cell hyperplasia – Hemophagocytic syndromes – Whipple disease – Vascularization of sinuses – Lymphangiogram effect
Follicular hyperplasia VS Follicular lymphoma
Hyperplasia:
- -Polymorphic cells
- -↑ mitosis
- -Macrophages
- -Bcl-2 (-) and t(14;18)(-)
- -Architecture preserved
- -Variation in G.C.
- -No back to back follicles
Lymphoma:
- -Monotonous cells
- ↓ mitosis
- ↓ Macrophages absent
- -Bcl-2 (+) and t(14;18)(+)
- -Architecture effaced
- -Little variation in G.C.
- -Back to back follicles
Castleman lymphadenopathy
– Mediastinal lesions – Regressed germinal centers – broad mantle zone, onion skin – dendritic reticulum cells – Interfollicular vascularity—lollipop – HHV8 – Mulitcentric Castleman disease worse prognosis – Multicentric Castleman disease assoc w POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin abnormalities)
HIV related lymphadenopathy
Three stages are seen:
Follicular hyperplasia
Follicular involution
Lymphocyte depletion
TOXOPLASMA LYMPHADENOPATHY
Follicular Pattern
• CLINICAL – Asymptomatic or fever, cervical lymph nodes – Organism: Toxoplasma gondii ARCHITECTURE/CYTOLOGY - Follicular hyperplasia - Epithelioid histiocytes near GC - Monocytoid B-cells in sinuses - Serology confirms diagnosis
INFECTIOUS MONONUCLEOSIS
Paracortical pattern
• CLINICAL FEATURES
– Usually self limited, usually cervical lymph nodes, teens presenting with infections
ARCHITECTURE /CYTOLOGY
- Paracortical proliferation of immunoblasts
- Sinuses distended by monocytoid B cells or immunoblasts
- Focal necrosis/apoptosis
- Hodgkin’s-like cells sometimes
- LMP(+) or EBER(+)
- Diff dx: DLBCL
Acute: IgM + IgG VCA Heterophile Ab (monospot) react w sheep or horse RBC
Remote: IgG EBNA, IgG VCA
CD8+ T cells stop EBV infected B cells from circulating
CD30+
DERMATOPATHIC LYMPHADENOPATHY
Paracortical pattern:
CLINICAL
– Chronic dermatoses may be present but the most florid reactions are seen with exfoliative dermatitis
ARCHITECTURE/CYTOLOGY
- Paracortex expansion
- Many pale histiocytes, some with with melanin
- Langerhans cells and interdigitating reticular cells
- Atypical T cell should be absent
- Mycosis Fungoides must be considered if confluence is present
HISTIOCYTIC NECROTIZING LYMPHADENITIS
• CLINICAL
– Kikuchi-Fujimoto disease—Asian, women, mean age 30 years
– Usually cervical lymph nodes
– Serologic tests for organisms negative (CMV, EBV, Toxo.)
– Self limiting disease
– Forme fruste of SLE
ARCHITECTURE/CYTOLOGY
- Necrosis with karyorrhectic dust
- Acute inflammation is absent (polys and eos)
- Plasmacytoid monocytes, cresentic histiocytes
- No plasma cells, unlike SLE
CAT SCRATCH LYMPHADENITIS
• CLINICAL
– Contact with cat
– The offending organism is Bartonella henselae
ARCHITECTURE/CYTOLOGY
Suppurative granulomas (stellate abscesses)
Neutrophils & monocytoid B-cell hyperplasia
Granulomas can be seen outside the L.N.
Warthin-Starry and Brown-Hopps stains
Rosai-Dorfman -
sinus histiocytosis with massive lymphadenopathy
• CLINICAL
– Bilateral cervical lymph nodes in a teen with fever
ARCHITECTURE/CYTOLOGY
Distended sinuses with foamy histiocytes
Emperipoiesis (inflam cells in histiocytes)
No erythroid phagocytosis (hemophagocytic
syndrome)
S-100(+), CD68(+), lysozyme (+)
Rosai-Dorfm
Hemophagocytic syndrome
Viruses, T-cell lymphoma, X-linked syndrome,
Erythrophagocytosis, viral inclusions
BACILLARY ANGIOMATOSIS
• CLINICAL
– Immunodeficient patients, lymph nodes draining skin lesion
– Organism Bartonella henselae
ARCHITECTURE/CYTOLOGY
- Vascular nodular parenchymal proliferation
- Amphophilic and eosinophilic material
- Vascular spaces are lined by plump endothelium
- Warthin-Starry stain shows organisms
Bacilary angiomatosis VS Kaposi sarcoma
Bacilary angiomatosis -
- Plump endothelial cells
- Little atypia
- Pos for organisms
- HHV8 -
Kaposi sarcoma-
- Spindle shaped cells;
- Slit shaped vessels
- More atypic, mitosis (+)
- Neg for organism
- HHV8 +
CLL/SLL DEFINITION
A neoplasm of monomorphic small, round
B-lymphocytes admixed with
prolymphocytes and paraimmunoblasts
forming pseudofollicles.
CLL/SLL makes up 6.7% of all lymphomas
CLL/SLL - Pseudofollicles
• Low magnification
- Spherical structures
- Pale staining
- Poorly defined
- Never surrounded by mantle cell zone
• High magnification --Cells loosely packed together with clear spaces often separating cells --Prolymphocytes (cells with one centrally placed prominent nucleolus)
CLL/SLL - Peripheral Blood
• absolute lymphocytosis
• prolymphocytes less than 10%
- smudge cells
CLL/SLL Phenotyping
Positive:
CD20--weak CD79a CD5 (85%) CD23 (85%) CD43 (98%) CD11c IgM IgM and IgD cIg (5%)
Negative:
CD3
CD10
Cyclin D1 (90)%
CLL is really two diseases
Favorable
CD38, Zap70 negative
Post germinal center cell
Adverse
CD38, Zap70 positive
Naïve B-cell
CLL/SLL Immunoglobulin Gene Mutations
IgH variable chain mutations normally occur
during germinal center stage of B cell
maturation
CD38 and ZAP70 are surrogate markers for
IgH variable chain gene mutation status
B- CLL GENETICS
Normal karyotype 50%
Del(13q) 25% good px
Tri 12 30% atyp histology/poor px
Del(11q) 2% poor prognosis
Del(17p) 10% poor prognosis
Hairy Cell Leukemia
• Medium B cells w pale cytoplasm,
oval/reniform/beanshaped nuclei
• Pancytopenia, monocytopenia
• Spleen morphology
– Localized to red pulp w red pulp lakes
– Inconspicuous white pulp
• Bone marrow
– Often subtle infiltrate, dispersed B cells wi pale cytoplasm, “fried egg appearance”
– ↑ reticulin fibrosis with dry tap
• Lymph node
– Paracortical infiltrate with sparing of follicles.
Hairy Cell Leukemia
• Phenotype
– Bright CD11c, CD25, CD103,
– Annexin A1, TRAP, DBA.44 positive
• Treatment
– High response rates to purine analogues, 2CDA
NO CHOP
Hairy cell leukemia variant
- Leukocytosis,
- Presence of monocytes,
- Prominent nucleoli like PLL
- Missing CD25 or CD103
- Resistant to HCL therapy
- Poor prognosis
- WHO 2008, these cases are not thought to be biologically related to HCL
Follicular lymphoma
•BCL-2+ ↓with grade with nearly
100% positive in grade 1 and 75%
grade 3
•BCL-2 often - in cutaneous follicular
lymphoma
•t (14;18)(q32;q21) present in 90% of
FL leads to overexpress BCL2 protein
•t (14;18) not sufficient to diagnose FCL detectable by PCR in some normal subjects
also found in 15-20% DLCBCL
- PCR is limited based on variation in the breakpoint involving BCL2.
- MBC and mcr breakpoints account for 70% of cases
- FISH detects nearly all breakpoints
Mantle Cell lymphoma
• Clinical
–Lymphomatous polyposis is mantle cell which studs the GI tract
• Phenotype
– CD20+, CD5+ (90%), CD43+, BCL-2+,
and nuclear BCL-1+ (80% cases)
• Genotype
– t (11;14) with rearrangement and
over-expression of BCL-1 (cyclin D1, PRAD1)
– 13q14 deletion and trisomy 12 frequent (yes, similar to CLL)
Marginal zone lymphoma
1. Malignant – Monocytoid cells – Plasmacytoid cells – Dutcher bodies – Expanded\confluent marginal zones – Lymphoepithelial lesions 2. Reactive – Reactive germinal centers may be colonized by marginal zone cells
Marginal zone lyphoma - genetics
– t (11;18) in 25-50% MALT
– t(11;18) not in primary nodal MZL
– t(11;18) not in MALT with DLBCL
– t (11;18) resistant to antibiotic therapy
Marginal zone lymphoma - precursor legions
- In gastric MZL H. pylori infection is 90%
- Sjogren syndrome—44 fold increase
- Hashimoto thyroiditis
- Hepatitis C
- Borrelia burgdorferi (Lyme dz), skin
- Campylobacter jejuni, eye
WHO 2008 Waldenstrom macroglobulinemia
• WM is defined as LPL with bone marrow involvement + IgM monoclonal gammopathy of any concentration • IgM paraprotein without LPL is not WM • Level of IgM paraprotein is irrelevant
Lymphoplasmacytic lymphoma
• Morphology–small B lymphocytes, plasmacytoid lymphocytes and plasma cells, Dutcher bodies
• Clinical—Hyperviscosity (30%), Neuropathy (10%), Cryoglobulinemia
• Immuno–CD5-, CD10-, CD23-
• Molecular–No recurrent abnormality
PAX5 translocation (t(9;14)) not seen
