Kutane T-Zelllymphome · 28/01/2019 · Epidermotropes Infiltrat durch maligne T-Zellen . Typische...

Kutane T-Zelllymphome

Alexandar Tzankov

Cutaneous T-cell and NK-cell lymphomas

• Mycosis fungoïdes and variants

• Sézary syndrome

• Adult T-cell leukemia/lymphoma

• CD30+ lymphoproliferative disorders incl. cALCL

• Subcutaneous panniculitis-like (αβ) T-cell lymphoma

• EBV+ cutaneous lymphomas:

– extranodal NK/T-cell lymphoma, nasal type

– EBV+ LPD of childhood

• Other (rare) cutaneous T-cell lymphomas

WHO 2018

Willemze et al. Blood 1997

Prognose der kutanen T-Zelllymphome


• Mycosis fungoïdes and variants, 5,5/1.000.000/J, M 2x>F

• Sézary syndrome








WHO 2018

Epidermotropes Infiltrat

durch maligne T-Zellen

Typische klinische Evolution als

wichtig(st)es Diagnostikum

Erythrodermie

Tumoren

Plaques

Patches

t Diagnose Vorstadien Jahre Dekaden später

Die Biologie hinter der Stadienevolution

Nebozhyn e

t al. B

lood 2

006

Wong e

t al. B

r J H

aem

ato

l 2011


• JAK3 oder zumindest STAT3

• Genexpression

–Skin-homing Chemokine

(CCR4, CCR10)

–Gene des Th1 T-Zellphänotyps

(STAT4, Tbet)

–Gene des Th2 T-Zellphänotyps

(GATA3)

– IL5,IL10


Fallbeispiel

Merke

• Integrative Diagnose

• Pautier Mikrobaszesse spezifisch aber selten

• Meist CD4+, oft CD7-, gelegentlich CD8+ (Kinder)

• Oft PD1+, ICOS+, CD30+ in EZ, GATA3>Tbet

• Zahlreiche Varianten

– Follikulotrope MF, Pagetoide Retikulose, garnulomatöse

schlaffe Haut

• DD

– Ekzem & Co

– CD8+ aggressives epidermotropes TCL (Klinik! Nekrose)


• Mycosis fungoides and variants, 5,5/1.000.000/J, M 2x>F

• Sézary syndrome: erythroderma+lymphadenopathy+Sézary cells








WHO 2018

Fallbeispiel

Merke

• Integrative Diagnose

• Kann das Endstadium einer MF oder aber primär

entstehen

• Typisches Mutationsprofil von TCL

– RHOA, CD28, JAK3, PLCG1, CARD11 etc.











WHO 2018

Lymphomatoide Papulose

CD30

Fallbeispiel

CD3

CD30

CD8

CD2 CD7

CD5

CD30

CD4

Fallbeispiel

Primary cutaneous CD30+ lympho-

proliferative diseases

• DD: transformed MF (clinical history!)

• Lymphomatoid papulosis (LyP)

– Recurrent, selfhealing papulonodular/papulonecrotic disease

– The clinical presentation is part of the disease definition!

– 20% association with syn- or metachronous MF, cALCL, HL

– Mostly CD4+, type D and E CD8+

• Primary cutaneous anaplastic large cell lymphoma

– Papules, nodules, ulcerating tumors, 20% multifocal

– Extracutaneous lesions in 10%, mainly LN

– CD4+, granzyme B/TIA1/perforin+, EMA-, ALK-

– IRF4 and TP63 rearrangements like in sALCL

– NPM1-TYK2 fusions seem specific for cALCL






• Subcutaneous panniculitis-like (αβ) T-cell lymphoma: SLE!





WHO 2018

Blood 2008 111:838-845

Fallbeispiel

Merke

• Patienten leiden of an SLE und die D zu Lupus-

Pannikulitis kann schwer sein:

– HLH, Fehlen von Plasmazellen und CD123+ PDC

suggestiv für TCL

• Definitionsgemäss αβ+

• Nicht epidermotrop







• EBV+ cutaneous lymphomas (PATHOBASIC 1):




WHO 2018

EBV-associated TCL in the skin

• Extranodal NK/T-cell lymphoma, nasal type

• EBV+ T/NK-cell LPD of childhood (adolescents)

https://pathobasic.files.wordpress.com/2018/10/2018-10-16_t-nhl.pdf








NK/T-cell lymphoma, nasal type

• Leukemic counterpart: aggressive NK-cell

leukemia

• Integrative diagnosis (mostly in endemic regions or

in emigrants from these regions) of clinical,

histopathologic and phenotypic findings

– almost always extranodal: nasal, skin, testes

– lymphocytosis, organomegaly, lymphadenopathy

– accompanying hemophagocytic syndrome

– CD2+, cCD3+, CD56+, TIA1+, granzyme B+

– EBER+, LMP1-/dim, EBNA2- (latency type 2)

– STAT3, STAT5B, JAK3, PTPRK … TP53 (!) mutations

CD3 EBER

NK/T-cell lymphoma, nasal type

NK/TCL in the bone marrow

CD3

EBER

Geographic distribution of HLA-A*0201 and nasal NK/TCL

Trogocytosis by NK/T cells

in HLA-A*0201 deficiency

EBV+ T/NK-cell LPD of childhood

• New classification encompassing EBV+ HPS and

systemic CAEBV (of T-cell type)

• Integrative diagnosis in endemic regions or in

emigrants from these regions of clinical, serologic

(VCA IgG titer height, IgE), histopathologic and

phenotypic findings

– children and adolescents

– skin rash, eruptions, uveitis, diarrhea, vasculitis

– high EBV DNA in the blood (million copies/ml)

– accompanying hemophagocytic syndrome

• Shortly after primary infectionCD8 or in CAEBVCD4

– Genetic defects in immune response to EBV

• without acquired immunosuppression

• EBER+, LMP1-/dim, EBNA2- (latency type 2)

• Generalized diseases with various clinical course

– Systemic EBV+ TCL – fulminant

– CAEBV – progressive, median survival in adults <5y

– Hydroa vacciniforme-like LPD – slowly progressive

– Severe mosquito bite allergy – progressive with

increased NK leukemia risk

EBV+ T/NK-cell LPD of childhood

CD8 > CD56 > CD4

CD2

CD5

EBER/CD

3

Generalized spread

EBER/CD

3







• EBV+ cutaneous lymphomas (PATHOBASIC 1):




WHO 2018

• Primary cutaneous CD4+ T-cell LPD

– head and scalp

– non-epidermotropic; CD4, PD1, BCL6+/CD10-

– occasionally with follicles and B-cell abundance

• Primary cutaneous acral CD8+ TCL (of the ear)

– ears, nose, acral sites

– dense, non-epidermotropic; CD8, CD68, TIA1+

• Primary cutaneous γδ+ TCL

– very aggressive (part of the definition!) with HLH

– panniculitic and epidermotropic, CD4 and 8-, cytotoxic marker+

• Primary cutaneous CD8+ aggressive epidermotropic TCL

– very aggressive (part of the definition!) with skin necrosis

– epidermotropic, cytotoxic marker+, CD2, 5 and 30-

Other cutaneous TCL

Kutane T-Zelllymphome · 28/01/2019 · Epidermotropes Infiltrat durch maligne T-Zellen . Typische...

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