Simon Haefliger. Pathologie. Fallvorstellung
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1 Simon Haefliger Pathologie Fallvorstellung
2 Castleman s disease Historical perspective Classification Epidemiology and clinical aspects Microscopic caracteristics Pathogenesis
3 Historical perspective First description in 1956 by Dr. Benjamin Castleman, a pathologist at Massachusetts General Hospital.
4 Historical perspective «A series of thirteen cases of mediastinal masses ressembling thymoma grossly and microscipically are shown to be a peculiar form of lymph node hyperplasia characterized by marked capillary proliferation»
5 Historical perspective Angiofollicular lymph node hyperplasia Giant lymph node hyperplasia Angiomatous lymphoid hamartoma Benign giant lymphoma Follicular lympho-reticuloma
6 Historical perspective Castleman s description Multicentric presentation Gaba AIDS association Lachant HHV-8 Association Soulier
7 Castleman s disease Historical perspective Classification Epidemiology and clinical aspects Microscopic caracteristics Pathogenesis
8 Classification CLINICAL HISTOLOGICAL
9 Unicentric vs Multicentric UNICENTRIC VARIANT: Single lymph node or silitary lymph node chain Rarely associated with constitutional symptoms MULTICENTRIC VARIANT: > 1 lymph node chains involved Frequently associated with epidsodic systemic symptoms
10 Classification CLINICAL HISTOLOGICAL HISTOLOGICAL
11 Hyalinized vessels Plasma cell +++ in the interfollicular zone
12 Classification CLINICAL HISTOLOGICAL HHV8+ vs HHV8- HISTOLOGICAL
13 HHV8+ versus HHV8- Multicentric angiofollicular lymph node hyperplasia (Castleman's disease) in patients with the AIDS. Lachant and colleagues, Kaposi's sarcoma-associated herpesvirus-like (HHV8) DNA sequences in multicentric Castleman's disease. Soulier and colleagues, 1995.
14 Classification Unicentric variant HHV8+ associated multicentric variant Idiopathic (HHV8-) multicentric variant = imcd
15 Historical perspective Angiofollicular lymph node hyperplasia Giant lymph node hyperplasia Angiomatous lymphoid hamartoma Benign giant lymphoma Follicular lympho-reticuloma
16 Castleman s disease Historical perspective Classification Epidemiology Microscopic caracteristics Pathogenesis
17 Epidemiology Rare disease, heterogenous data UCD: good prognosis, mean age (34 years) MCD: agressive disease, mean age ( +/- 60 years) The exact incidence is unknown
18 MCD, a agressive disease. 5 years mortality rates!!!! NHL HL BC
19 Historical perspective Angiofollicular lymph Node hyperplasia Giant lymph node hyperplasia Angiomatous lymphoid hamartoma Benign giant lymphoma Follicular lympho-reticuloma
20 Epidemiology, MCD Idiopathic multicentric Castleman's disease: a systematic literature review, Fajgenbaum DC. Lancet Haematol. 2016
21 Castleman s disease Historical perspective Classification Epidemiology Microscopic caracteristics Pathogenesis
22
23 Hyaline vascular variant Hyalinized vessels Expanded mantle zone Atrophic germinal center «onion skin» and lollipop sign Dysplastic FDC
24 Atrophic Hyaline germinal vascular center variant Hyalinized vessels Expanded mantle zone
25 Atrophic Hyaline germinal vascular center variant Hyalinized vessels Expanded mantle zone «onion skin»
26 lollipop sign m_saeed/publication/ /figure/fig2/ eman-disease-hyaline-vascular-type-b-cellfollicle-with-typical-expanded-mantle.png
27 Plasma cell variant Hyperplastic germinal center Diffuse plasma cells between follicles
28 Hyaline vascular variant Hyperplastic follicle center Plasma cell infiltration
29 Plasma cell variant Hyperplastic germinal center Diffuse plasma cells between follicles Plasmablastic subtyp specific for HHV8 + Plasma cell variant can exhibit hyaline vascular change!!!! Mixed variant?
30 Difficulties Castleman-like changes can be seen in other disease Castleman disease = group of 3 disease with common morphological features In fact the term Castleman disease should be avoided!!!!
31 Clinico-pathology diagnosis Lymph node with Castleman like features 1 st Step: Exclusion of other diagnosis (EBV, SLE, HL ) 2 nd Step UCD: 1. Histology 2. HHV8 Status 3. Clinic 3 rd Step MCD: 1. Histology 2. HHV8 Status 3. Clinic
32 Castleman s disease Historical perspective Classification Epidemiology Microscopic caracteristics Pathogenesis
33 Pathogenesis, MCD Old model = benign plasma cell proliferation IL-6 Polyclonality!!! INFLAMMATORY DISEASE
34 Pathogenesis, MCD HHV8 1. Paraneoplasic hypothesis 2. Inflammatory disease 3. Viral hypothesis virus IL-6 like IL-6 Brandt et al Screpanti et al T-reg Il-6 Il-1 TNF-alpha VEGF Constitutional Symptoms Fajgenbaum DC, van Rhee F, Nabel CS. Blood Review.
35 Pathogenesis, UCD No association with HHV8 Role of IL-6? Possible precursor of dendritic cell sarcoma? 10-20% of FDC sarcoma have been shown to be associated with Castleman s disease
36 Pathogenesis, UCD
37 Paraneoplastic associated MCD P O E M S Polyneuropathy Organomegaly Endocrinopathy Monoclonal protein Skin changes
38 Associated syndromes P Polyneuropathy T Thrombocytopenia O Organomegaly A Ascites E Endocrinopathy F Myelofibrosis M Monoclonal protein R Renal dysfonction S Skin changes 0 Organomegaly
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