Lymph node I and II

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Lymph node I and II

• Aaron Auerbach M.D M.P.H

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A copy of this lecture can be found at

• http//www.afip.org/consultation/hemepath/

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Lecture outline

• Reactive lymph node
• Small B cell lymphoma
• Large B cell lymphoma
• Hodgkin lymphoma
• T cell lymphoma

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Tingible body macrophages
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CD20
CD3
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Bcl-6
CD10
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CD21
Bcl-2
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IgD mantle zones
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PATTERNS OF BENIGN LYMPHADENOPATHY

• FOLLICULAR
• Follicular Hyperplasia
• Giant lymph node hyperplasia-hyaline vascular
  (Castleman disease)
• Progressively transformed germinal centers
• HIV-related lymphadenopathy
• Rheumatoid lymphadenopathy
• Syphilitic lymphadenopathy
• 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
• SINUS PATTERN
• Sinus histiocytosis
• Langerhans cell histiocytosis (EG, H-X)?

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FOLLICULAR PATTERN
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Follicular hyperplasia VS Follicular lymphoma

• --Polymorphic cells
• --? mitosis
• --Macrophages
• --Bcl-2 (-) and t(1418)(-)
• --Architecture preserved
• --Variation in G.C.
• --No back to back follicles

• --Monotonous cells
• -- ? mitosis
• -- ? Macrophages absent
• --Bcl-2 () and t(1418)()
• --Architecture effaced
• --Little variation in G.C.
• --Back to back follicles

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FL
FH
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FH
FL
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NEXT 5 SLIDESWHAT IS YOUR DIAGNOSIS?
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Follicular hyperplasia
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Multiple germinal centers in one follicle
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Castleman lymphadenopathy

• Mediastinal lesions
• Regressed germinal centers
• broad mantle zone, onion skin
• dendritic reticulum cells
• Interfollicular vascularitylollipop
• HHV8
• Mulitcentric Castleman disease worse prognosis
• Multicentric Castleman disease assoc w POEMS
  (polyneuropathy, organomegaly, endocrinopathy,
  monoclonal gammopathy, and skin abnormalities)

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HIV related lymphadenopathy
Three stages are seen Follicular hyperplasia
Follicular involution Lymphocyte depletion
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HIV related lymphadenopathy, follicular
hyperplasia
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HIV related lymphadenopathy, follicular involution
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LYMPHOCYTE DEPLETION
Small lymph nodes with fibrosis,? Follicles, ?
FDC, Histiocytes with phagocytized RBC
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Next 3 slides
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Epithelioid histiocytes near GC
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Monocytoid B-cell hyperplasia
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WHAT IS YOUR DIFFERENTIAL DIAGNOSIS?
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Follicular patternTOXOPLASMA LYMPHADENOPATHY

• 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
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Paracortical patternINFECTIOUS MONONUCLEOSIS

• 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 - Hodgkins-like
cells sometimes
- LMP() or EBER() - Diff dx DLBCL
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CD30
LMP1
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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
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Paracortical patternDERMATOPATHIC
LYMPHADENOPATHY

• 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
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CD1a
S-100
Both IRCs and LCs stain for CD1a and S100
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HISTIOCYTIC NECROTIZING LYMPHADENITIS

• CLINICAL
• Kikuchi-Fujimoto diseaseAsian, 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
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Crescentic histiocytes
karyorrhexis
CD68
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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
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Warthin-Starry
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WHAT IS YOUR DIAGNOSIS?
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S-100
CD68
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Rosai-Dorfmansinus 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 ()
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Hemophagocytic syndrome
Viruses, T-cell lymphoma, X-linked
syndrome, Erythrophagocytosis, viral inclusions
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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
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Vascular nodular parenchymal proliferation
Vascular spaces are lined by plump endothelium
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Warthin-Starry
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BA VS KS

• - Plump endothelial cells
• - Little atypia
• - Pos for organisms
• - HHV8 -

• - Spindle shaped cells
• - Slit shaped vessels
• - More atypic, mitosis ()
• - Neg for organism
• - HHV8

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Lecture outline

• Reactive lymph node
• Small B cell lymphoma
• Large B cell lymphoma
• Hodgkin lymphoma
• T cell lymphoma

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Morphology only, what is your diagnosis?
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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
Derived from data from the International Lymphoma
Study Group. Blood, Vol. 89 No. 11 (June 1),
1997 pp. 3909-3918
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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)

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Peripheral Blood

• absolute lymphocytosis
• prolymphocytes less than 10

Basket cells/smudge cells
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Phenotyping

• Positive Negative
• CD20 --weak CD3
• CD79a CD10
• CD5 (85) Cyclin D1 (90)
• CD23 (85)
• CD43 (98)
• CD11c
• IgM
• IgM and IgD
• cIg (5)

Cant use just immuno. If you are wrong 15 of
the time you will be fired!!!
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CLL is really two diseases!
Favorable CD38, Zap70 negative
Adverse CD38, Zap70 positive
Naïve B-cell
Post germinal center cell
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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

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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

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What is your diagnosis?
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Hairy Cell Leukemia (HCL)

• 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.

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HCL
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Hairy cell leukemiathe bright one!
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HCL

• Phenotype
• Bright CD11c, CD25, CD103,
• Annexin A1, TRAP, DBA.44 positive
• Treatment
• High response rates to purine analogues, 2CDA NO
  CHOP

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CLL
HCL
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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

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FL
CD10
BCL-2
BCL-6
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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 (1418)(q32q21) present in 90 of FL leads to
  overexpress BCL2 protein
• t (1418) 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

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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 (1114) with rearrangement and
• over-expression of BCL-1 (cyclin D1, PRAD1)
• 13q14 deletion and trisomy 12 frequent (yes,
  similar to CLL)

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MCL
BCL-2
BCL-1
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PCR T(1114)(q13q32)
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FISH
BCL1 and IgH loci detected via FISH. Probe
signals are co-localized at translocation
breakpoints (arrows).
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CD20
MCL
CD3
CD5
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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

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Marginal zones reactive and neoplastic
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Follicular colonization
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Intranuclear inclusion
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Lymphoepithelial lesions
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T(1118) MLT and API2 genes

• t (1118) in 25-50 MALT
• t(1118) not in primary nodal MZL
• -- t(1118) not in MALT with DLBCL
• t (1118) resistant to antibiotic therapy

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PRECURSOR LESIONS

• In gastric MZL H. pylori infection is 90
• Sjogren syndrome44 fold increase
• Hashimoto thyroiditis
• Hepatitis C
• Borrelia burgdorferi (Lyme dz), skin
• Campylobacter jejuni, eye

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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

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Lymphoplasmacytic lymphoma

• Morphology--small B lymphocytes, plasmacytoid
  lymphocytes and plasma cells, Dutcher bodies
• ClinicalHyperviscosity (30), Neuropathy (10),
  Cryoglobulinemia
• Immuno--CD5-, CD10-, CD23-
• Molecular--No recurrent abnormality
• PAX5 translocation (t(914)) not seen

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LPL
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Lecture outline

• Reactive lymph node
• Small B cell lymphoma
• Large B cell lymphoma
• Hodgkin lymphoma
• T cell lymphoma

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What is your diagnosis?
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Burkitt Lymphoma
3 CLINICAL VARIANTS
ENDEMIC
SPORADIC
IMMUNO SUPPRESSED
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ENDEMIC BURKITT LYMPHOMA
Africa Children 4-7 y/o Male Malaria Jaw/faci
al bones 95 EBV
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Sporadic Burkitt lymphoma

• adult median 30 y.o.
• 30-50 of childhood lymphomas
• EBV positive cells in 30 of cases

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Immunophenotype, molecular

• Immuno
• -Positive for CD20, CD10 bcl-6
• -Ki-67 100 of cells
• -Neg for bcl-2, or weakly in 20
• Molecular
• -T(814) IgH/myc
• -T(28) myc/kappa
• -T(822) myc/lambda

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Factoids

• Translocation involving MYC is highly
  characteristic but not specific for Burkitt
  lymphoma
• No single parameter alone (ie morphology,
  genetics, IHC) can be used as the gold standard
  for the diagnosis of Burkitt lymphoma
• A combination of several techniques is required
  for dx.
• The 2008 WHO does not recognize atypical Burkitt
  lymphoma as a distinct entity.
• Instead, it acknowledges that there are cases of
  Burkitt lymphoma with ?nuclear pleomorphism,
  which previously would have been called atypical
  Burkitt

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This used to be a simplified topic

• You have a nasty looking tumor that you think is
  lymphoma with dispersed cells and no gland
  formation, then
• 1. You look at the size of the cellslarge
  lymphoid cells
• 2. You get immuno (CD20) to prove there are B
  cells
• 3. You can make a diagnosis of diffuse large B
  cell lymphoma

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DLBCL

• Other lymphomas of large B cells
• -Primary mediastinal (thymic)
• large B cell lymphoma
• -Intravascular large B cell
• lymphoma
• -DLBCL associated w chronic
• inflammation
• -Lymphomatoid granulomatosis
• -ALK-positive LBCL
• -Plasmablastic lymphoma
• -LBCL arising in HHV8
• multicentric Castlemans
• -Primary effusion lymphoma
• Borderline cases
• Discussed later

• Common morphologic variant
• -Centroblastic
• -Immunoblastic
• -Anaplastic
• Molecular subgroups
• -Germinal centre B cell like
• -Activated B cell like
• IHC subgroups
• -CD5 DLBCL
• -Germinal centre B cell like
• -Non germinal centre B cell
• like
• Subtypes
• -T cell/histiocyte-rich large B
• cell lymphoma
• -Primary DLBCL of the CNS
• -Primary cutaneous DLBCL, leg
• type
• -EBV DLBCL of the elderly

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Gene expression profiling identified 2 subgroups
of DLBCL
Alizadeh et al, Nature 2000 403 503-510

• Germinal center like
• Activated B cell

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Subtypes of DLBCL

• T cell/histiocyte-rich large B cell lymphoma
• Primary DLBCL of the CNS
• Primary cutaneous DLBCL, leg type
• EBV DLBCL of the elderly

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T cell/histiocyte-rich large B cell lymphoma
CD20
CD3
Large cells lt10 of total cellularity Can look
like centroblasts, immunoblasts, LH cells, RS
cells CD20, LCA, CD30/-, rare CD15, bcl-6,
bcl2/-
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Primary cutaneous DLBCL, leg type
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DLBCL, leg type

• Old diagnosis for E.O.R.T.C.
• New diagnosis from WHO
• elderly females
• Aggressive
• Tx, combination chemotherapy
• 5 year survival 55 (Blood, 2005)
• Histology
• Immunoblastic
• Round cell morphology

Bcl-2
Bcl-6
Immunos -Strong bcl-2, unlike cutaneous
follicular lymphoma - MUM1/IRF, FOXP1, CD10
usually -, BCL-6,
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Other lymphomas of large B cells

• Primary mediastinal (thymic) LBC lymphoma
• Intravascular large B cell lymphoma
• DLBCL associated w chronic inflammation
• Lymphomatoid granulomatosis
• ALK-positive LBCL
• Plasmablastic lymphoma
• LBCL arising in HHV8 multicentric Castlemans
• Primary effusion lymphoma

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Mediastinal (thymic) Large B-cell Lymphoma

• Clinical
• B cell lymphoma in mediastinum
• May have superior vena cava syndrome
• 20-40 year old women

compartmentalizing fibrosis
Immunos/molecular Lack of surface immunoglobulin
by flow But IgH rearrangement by PCR B-cell
markers Bcl-2 and bcl-6 can be CD30 (80),
but weak CD15 only rarely MAL protein
B cells w ?clear cytoplasm
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Lymphomatoid granulomatosis

• Angiocentric and angiodiestructive
  lymphoproliferative dz of extranodal sites,
  composed of EBV B cells and reactive T cells.
• Used to be thought of as a T cell lymphoma
• Lung, brain, liver, kidney skin

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LYG
EBER
CD79
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Lecture outline

• Reactive lymph node
• Small B cell lymphoma
• Large B cell lymphoma
• Hodgkin lymphoma
• T cell lymphoma

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Hodgkin lymphoma

• WHO classification
• Nodular lymphocyte predominant
• Classical
• Nodular sclerosis
• Mixed cellularity
• Lymphocyte-rich
• Lymphocyte-depleted

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Nodular Lymphocyte Predominant Hodgkin lymphoma
L H cells with 1 large folded nucleus, and
scant cytoplasm (popcorn cells) Absence of PMNs
and eosinophils Progressive transformation of
germinal centers (PTGC) is associated
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Immunophenotype

• CD45, CD20, J-chain and EMA
• CD3 and CD57 T-cells in background ring
  malignant cells
• Nearly all cases are CD15 CD30 neg
• Oct2 and BOB.1 consistently present whereas in
  classic HL one or both will be absent

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PROGRESSIVE TRANSFORMATION OF GERMINAL CENTERS
- Large follicles (3-4 times normal) -
inward migration of perifollicular small B cells
and activated T cells into the germinal
centers - Absent L and H cells - May
proceed, follow or accompany NLPHD
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Classic Hodgkin lymphoma

• -- 95 of HL with bimodal age with
• 15-35 year peak and 2nd peak late life
• -- Mediastinal

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Nodular Sclerosis Hodgkin lymphoma

• CD30, CD15 (75-85) CD45 neg, LMP-1 and EBER
  variable, BSAP(PAX5)
• RS cells in up to 40 of cases

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Mixed cellularity Hodgkin lymphoma (MCHL)
Interfollicular growth pattern may be seen May
have interstitial fibrosis but no capsular
thickening or broad bands of collagen
fibrosis EBV-LMP- highest frequently-75 Mediastin
al involvement uncommon
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Lymphocyte rich Hodgkin lymphoma
nodular growth pattern Regressed germinal
centers RS cells in mantle zone No eos PMNs in
background
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Lecture outline

• Reactive lymph node
• Small B cell lymphoma
• Large B cell lymphoma
• Hodgkin lymphoma
• T cell lymphoma

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T CELL LYMPHOMA BY LOCATION
Peripheral T-cell lymphoma, NOS Angioimmunoblastic
T-cell lymphoma Anaplastic large cell lymphoma
Lymph node
Adult T-cell leukemia/lymphoma T-cell
prolymphocytic leukemia T-cell large granular
lymphocytic leukemia Aggressive NK-cell
leukemia T cell lymphoblastic lymphoma
Leukemia/bone marrow
Enteropathy-type T cell lymphoma Hepatosplenic
T-cell lymphoma Extranodal NK/T-cell lymphoma,
Nasal type Subcutaneous panniculitis-like T cell
lymphoma Gd cutaneous T cell lymphoma Mycosis
fungoides Primary cutaneous CD30 T cell LPD
Extranodal
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PERIPHERAL T-CELL LYMPHOMA, NOS

• T cell lymphoma in which cases do not better fit
  into a different category
• HE
• clear cytoplasm
• Inflammatory background of eosinophils and
  epithelioid histiocytes
• Lymphoepithelioid variant (Lennert lymphoma)

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They typically show increased clear cytoplasm and
have eosinophils or plasma cells
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AILT
Tubinal 1988, Siegert 1992, Paulier 1999
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AILT
Arborizing blood vessels w PAS material
Follicular dendritic cells CD23 surround vessels
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CD10 positive in T cells
CD3
CD10
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EBER
CD20
CD3
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CXCL 13

• Found in T cells in germinal centers
• Expressed in follicular dendritic cells
• PD1 also .

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Step1 Distribution of tumor
Peripheral T-cell lymphoma, NOS Angioimmunoblastic
T-cell lymphoma Anaplastic large cell lymphoma
Lymph node
Adult T-cell leukemia/lymphoma T-cell
prolymphocytic leukemia T-cell large granular
lymphocytic leukemia Aggressive NK-cell
leukemia T cell lymphoblastic lymphoma
Leukemia/bone marrow
Enteropathy-type T cell lymphoma Hepatosplenic
T-cell lymphoma Extranodal NK/T-cell lymphoma,
Nasal type Subcutaneous panniculitis-like T cell
lymphoma Gd cutaneous T cell lymphoma Mycosis
fungoides Primary cutaneous CD30 T cell LPD
Extranodal
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Anaplastic large cell lymphoma

• Large cells with marked atypia
• Hallmark cells are large kidney shaped nucleus
  with eosinophilic paranuclear area
• Reed-Sternberg like cells, wreath-like
• Multinucleate
• Sinusoidal growth pattern
• Show perivascular rosetting, but does not destroy
  blood vessels.

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Anaplastic large cell lymphoma
Sinusoidal growth pattern
perivascular rosetting
Hallmark cells are large kidney shaped,
wreathlike nucleus
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CD45
CD43
EMA
CD30
ALK-1
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Translocations and fusion proteins involving ALK
Figure 7.
Stein, H. et al. Blood 2000963681-3695
NPM shuttles continuously between the cytoplasm
and nucleolus Cases with variant translocations
usually show ALK staining in the cytoplasm only
and are negative by PCR for NPM/ALK Therefore,
ALK immuno is a more sensitive diagnostic marker
than PCR
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ALCL

• ALCL is one of the T cell lymphomas that has the
  best responses to therapy. Alk has better px.

• Except with the small cell variant. In small
  cell variant,
• ALK positivity does not lead to a better
  prognosis.

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ATLL Clinical syndrome

• Caused by HTLV1
• Japan, Caribbean, central Africa,
• Lymphocytosis (62), lymphadenopathy (61), lytic
  bone lesions (36) HSM (61), skin lesions (61)
  hypercalcemia (73),
• Large polylobated flower cells
• Skin, epidermotropism w Pautrier-like
  microabscesses
• Bone marrow, tumor cells ?osteoclasts
• Dilated lymph node sinuses with tumor cells.
• Variants
• 1. Acute--leukemic
• 2. Lymphomatous variantlymphadenopathy
• 3. Chronic variantskin lesions
• 4. Smoldering variant--WBC normal

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Peripheral blood polylobated flower cell
Peripheral blood
Polylobated flower cell
skin
Lytic bone lesion
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Bone tumor and osteoclasts
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Phenotype

• T cell markers, CD4, CD5,
• HTLV1, FoxP3, CD25
• EBV-
• Cytotoxic markers -

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Immunos
FoxP3
CD25
FoxP3
Pics from internet
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Step1 Distribution of tumor
Peripheral T-cell lymphoma, NOS Angioimmunoblastic
T-cell lymphoma Anaplastic large cell lymphoma
Lymph node
Adult T-cell leukemia/lymphoma T-cell
prolymphocytic leukemia T-cell large granular
lymphocytic leukemia Aggressive NK-cell
leukemia T cell lymphoblastic lymphoma
Leukemia/bone marrow
Enteropathy-type T cell lymphoma Hepatosplenic
T-cell lymphoma Extranodal NK/T-cell lymphoma,
Nasal type Subcutaneous panniculitis-like T cell
lymphoma Gd cutaneous T cell lymphoma Mycosis
fungoides Primary cutaneous CD30 T cell LPD
Extranodal
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Step1 Distribution of tumor
Peripheral T-cell lymphoma, NOS Angioimmunoblastic
T-cell lymphoma Anaplastic large cell lymphoma
Lymph node
Adult T-cell leukemia/lymphoma T-cell
prolymphocytic leukemia T-cell large granular
lymphocytic leukemia Aggressive NK-cell
leukemia T cell lymphoblastic lymphoma
Leukemia/bone marrow
Enteropathy-type T cell lymphoma Hepatosplenic
T-cell lymphoma Extranodal NK/T-cell lymphoma,
Nasal type Subcutaneous panniculitis-like T cell
lymphoma Gd cutaneous T cell lymphoma Mycosis
fungoides Primary cutaneous CD30 T cell LPD
Extranodal
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Enteropathy - type T- cell lymphoma

• Associated with gluten-sensitive enteropathy
  (celiac disease) but occurs less commonly
  without gluten-sensitive enteropathy
• Jejunal involvement perforation common
• Stomach and colon not commonly affected
• Aggressive, death from multiple perforations

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ETTCL-Morphology

• 1. T cell lymphoma part
• Mixture of small and large lymphocytes
• A mass of lymphocytes
• 2. Gluten sensitive enteropathy part
• Intraepithelial T-cells in adjacent mucosa
• Villous atrophy

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Phenotype

• T cell markers
• CD8, but can also be negative
• CD103
• CD5-
• CD30/-, CD56/-
• Cytotoxic markers

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T cell lymphoma part
Small cell variant
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Gluten sensitive enteropathy part
CD3
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Gluten sensitive enteropathy part, glands
CD3
CD2
CD8
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CD7
CD56
Gluten sensitive enteropathy part glands
CD20
CD5
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Step1 Distribution of tumor
Peripheral T-cell lymphoma, NOS Angioimmunoblastic
T-cell lymphoma Anaplastic large cell lymphoma
Lymph node
Adult T-cell leukemia/lymphoma T-cell
prolymphocytic leukemia T-cell large granular
lymphocytic leukemia Aggressive NK-cell
leukemia T cell lymphoblastic lymphoma
Leukemia/bone marrow
Enteropathy-type T cell lymphoma Hepatosplenic
T-cell lymphoma Extranodal NK/T-cell lymphoma,
Nasal type Subcutaneous panniculitis-like T cell
lymphoma Gd cutaneous T cell lymphoma Mycosis
fungoides Primary cutaneous CD30 T cell LPD
Extranodal
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Hepatosplenic T cell lymphoma

• Young men
• Hepatosplenomegaly
• Often no lymphadenopathy
• Aggressive
• T cells in sinusoids of liver and spleen.
• Spares portal triads white pulp
• Most commonly Gd cells-- TCRd1, ßF1-, Usually
  CD4-/CD8-, but can be CD4-/CD8, CD5-, Tia, but
  perforin
• Iso 7q, trisomy 8

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Hepato part sinusoidal infiltrates
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Splenic part sinusoidal infiltrate
CD3
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Bone marrow sinusoids
CD3
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Step1 Distribution of tumor
Peripheral T-cell lymphoma, NOS Angioimmunoblastic
T-cell lymphoma Anaplastic large cell lymphoma
Lymph node
Adult T-cell leukemia/lymphoma T-cell
prolymphocytic leukemia T-cell large granular
lymphocytic leukemia Aggressive NK-cell
leukemia T cell lymphoblastic lymphoma
Leukemia/bone marrow
Enteropathy-type T cell lymphoma Hepatosplenic
T-cell lymphoma Extranodal NK/T-cell lymphoma,
Nasal type Subcutaneous panniculitis-like T cell
lymphoma Gd cutaneous T cell lymphoma Mycosis
fungoides Primary cutaneous CD30 T cell LPD
Extranodal
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Extranodal NK/T-cell lymphoma, Nasal type

• AKA polymorphic reticulosis, lethal midline
  granuloma, angiocentric lymphoma.
• Young/Asian
• Big midline facial tumor, but can be seen in
  other locations
• Angiocentric with necrosis
• Plasma cells, eos, macs
• Hemophagocytosis
• T cell markers, Surface CD3-, cytoplasmic CD3?
• CD56, CD57, cytotoxic markers, EBV

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Angiocentric
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Tumor cells and necrosis
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CD45
CD3?
CD43
CD56
TIA-1
EBER
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Step1 Distribution of tumor
Peripheral T-cell lymphoma, NOS Angioimmunoblastic
T-cell lymphoma Anaplastic large cell lymphoma
Lymph node
Adult T-cell leukemia/lymphoma T-cell
prolymphocytic leukemia T-cell large granular
lymphocytic leukemia Aggressive NK-cell
leukemia T cell lymphoblastic lymphoma
Leukemia/bone marrow
Enteropathy-type T cell lymphoma Hepatosplenic
T-cell lymphoma Extranodal NK/T-cell lymphoma,
Nasal type Subcutaneous panniculitis-like T cell
lymphoma Gd cutaneous T cell lymphoma Mycosis
fungoides Primary cutaneous CD30 T cell LPD
Extranodal
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Subcutaneous panniculitis-like T cell lymphoma

• Aggressive T cell lymphoma
• WHO distinguishes between aß and ?d
• ?ß are included in SPLTCL
• Gd are called cutaneous ?d T cell lymphoma
• Lesions are confined to subcutis
• Lymphocytes encircle fat lobules
• Septum involvement is mild
• Karyorrhexis and fat necrosis almost always
  present

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SPLTCL
From internet
Low power
High power
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Mycosis Fungoides

• Clinical-Scaly erythematous rash that progresses
  from patches/plaques and may form a solid skin
  tumor
• Disease has a long natural history, so patients
  may have non-specific infiltrates in the skin and
  rashes for years before diagnostic histology
  develops.
• Morphology-lymphocytes w cerebriform nuclei in
  dermis with extension to epidermis
  (epidermotropism)
• Pautrier abscesses are collections of malignant T
  cells in the epidermis
• Halos
• Dermal infiltratenon specific
• Usually CD4, rarely CD8
• USUALLY NO CYTOTOXIC FEATURES

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Epidermotropism
Beware cases of spongiosis can also have
epidermotropism
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Cerebriform nuclei
Cerebriform nucleiserpentine, folding
Lutzner et al, Blood
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Sezary Sydrome

• Exfoliative erythroderma, generalized
  lymphadeopathy and malignant (Sezary cells in the
  peripheral blood
• Spares bm

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Questions?
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The following are some extra charts for your
board studies
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T cell lymphoma molecular abnormalities
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LYMPHOBLASTIC LYMPHOMA VS. MANTLE CELL LYMPHOMA
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LBL VS BURKITT
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TCRLB vs. Nodular LP Hodgkins
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TCRLB vs. Classical Hodgkin
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