Castleman Disease (CD) (Oksenhendle BJH 2017)

 

HHV8 Infection

IL-6 pathway

Data used in these notes based on Oskenhendle case series >200 patients

 

Pathophysiology

 

Multicentric CD characterized by episodic inflammatory symptoms & reactive lymphadenopathy

Chaotic in behavior & life-threatening with MOF 2o to excess IL-6 & other cytokines

HHV8 infection appears to drive majority of cases. HIV also significant.

The excess IL-6 is viral in origin in HHV8 MCD, and human in iMCD

 

Classification

 

castlemans.png

 

TAFRO = Thrombocytopenia, Anasarca, BM fibrosis, Renal dysfunction & Organomegaly

IPL-type iMCD = Idiopathic Lymphadenopathy w/ Polyclonal Hyperimmunoglobulinaemia

 

Aggressiveness of disease

 

HIV neg HHV8 MCD > HIV pos HHV8 MCD > iMCD

 

Histology

 

UCD                – hyaline vascular morphology

HHV8 MCD     – large plasmablastic HHV8+ cells

iMCD               – plasmacytic morphology with polyclonal proliferation

 

Diagnostic Pathway

 

1.     Exclude diagnosis that present CD-like histopathology

a.     E.g. HL, NHL, POEMS, Plasmacytoma, AI (SLE, Sjogrens, IgG4 disease)

2.     Stage the disease – UCD includes multiple LN within a single station

3.     Immunohistochemistry for HHV8

4.     Context of HIV infection

 

UCD

 

Median age 35, M = F

Asymptomatic or mildly symptomatic

Severe complications rare but included:

-       paraneoplastic pemphigus, polyneuropathy, failure to thrive, BOOP, AIHA

 

Normal FBC

2 yr OS 98%

 

Mx: Surgical resection (<10% relapse), Radiothwerapy, W&W, Steroids, Tocilizumab, Rituximab

iMCD

 

Median age 47, M > F

Fever, splenomegaly, oedema, effusions, resp symptoms, renal impairment

Associations: Consanguinous parents, Hep C, IBD

 

Anaemia, Thrombocytosis/penia, Raised CRP, Low Albumin, Raised Ig’s

2 yr OS 100%

 

Mx: Steroids (50% response), Tociliz (100% response), Ritux (60% response), Etoposide, W&W

HIV negative HHV8 MCD

 

Fever, splenomegaly, oedema, effusions, resp symptoms, renal impairment

Haemophagocytic syndrome, Kaposi sarcoma

Associations: Consanguinous parents, Hep B/C, thymoma, MSM, immunosuppressant usage

 

Anaemia, Thrombocytosis/penia, Raised CRP, Low Albumin, Raised Ig’s

75% DAT +, 40% MGUS

2 yr OS 89%

 

Mx: Etoposide, Rituximab, Steroids, Tocilizumab

 

HIV positive HHV8 MCD

 

Median age 41

Fever, splenomegaly, oedema, effusions, resp symptoms, renal impairment

Haemophagocytic syndrome, Kaposi sarcoma

 

Anaemia, Thrombocytosis/penia, Raised CRP, Low Albumin, Raised Ig’s

75% DAT +, 40% MGUS

2 yr OS 77% (not statistically different to HIV- patients)

 

Mx: Etoposide, Combination Chemo, Steroids, Rituximab, Tocilizumab