11.28.07 castleman's doutova

7/28/2019 11.28.07 Castleman's Doutova

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CASTLEMANS

DISEASE.

DR. GULZAR ALI

MCPS RESIDENTNATIONAL MEDICAL CENTRE


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Also referred to as angiofollicular lymph node

hyperplasia (also known as angiofollicular lymph

node hyperplasia orgiant lymph node

hyperplasia ) is an uncommon

benign lymphoproliferative condition. It can affectseveral regions of the body although commonly

described as a solitary mediastinal mass.
http://radiopaedia.org/articles/missing?article%5Btitle%5D=lymphoproliferative+conditionhttp://radiopaedia.org/articles/missing?article%5Btitle%5D=lymphoproliferative+condition


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Background

Etymology

First described by Benjamin Castleman in

1956

follicular hyperplasia of lymph nodes withabnormally increased interfollicular

vascularity

Can be associated with Kaposi's sarcoma(KS), non-Hodgkin's lymphoma, Hodgkin's

lymphoma, and POEMS syndrome.


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Differential diagnosis

For thoracic lesions consider

If antero-superior : consider : differential for

an antero-superior medistinal mass

If posterior : consider : differential for a

posterior medistinal mas
http://radiopaedia.org/articles/differential-for-an-anterosuperior-mediastinal-masshttp://radiopaedia.org/articles/differential-for-an-anterosuperior-mediastinal-masshttp://radiopaedia.org/articles/differential-for-a-posterior-mediastinal-masshttp://radiopaedia.org/articles/differential-for-a-posterior-mediastinal-masshttp://radiopaedia.org/articles/differential-for-a-posterior-mediastinal-masshttp://radiopaedia.org/articles/differential-for-a-posterior-mediastinal-masshttp://radiopaedia.org/articles/differential-for-an-anterosuperior-mediastinal-masshttp://radiopaedia.org/articles/differential-for-an-anterosuperior-mediastinal-masshttp://radiopaedia.org/articles/differential-for-an-anterosuperior-mediastinal-masshttp://radiopaedia.org/articles/differential-for-an-anterosuperior-mediastinal-mass


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The differential diagnosis for a posterior mediastinal mass includes

neurogenic tumours

schwannoma

neurofibroma

malignant peripheral nerve sheath tumour

neuroblastic tumours

neuroblastoma

ganglioneuroma

non-neurogenic tumours

chordoma2

phaeochromocytoma3

paraspinal abscess

descending aortic aneurysm oesophageal neoplasm

hernias

hiatus hernia

Bochdalek hernia

lymphadenopathy orlymphoma 1

extramedullary haematopoiesis

foregut duplication cysts neurenteric cyst

oesophageal duplication cyst

thoracic meningocoele
http://radiopaedia.org/articles/neurogenic-tumourshttp://radiopaedia.org/articles/schwannomahttp://radiopaedia.org/articles/neurofibromahttp://radiopaedia.org/articles/malignant-peripheral-nerve-sheath-tumourhttp://radiopaedia.org/articles/neuroblastic-tumourshttp://radiopaedia.org/articles/neuroblastomahttp://radiopaedia.org/articles/ganglioneuromahttp://radiopaedia.org/articles/chordomahttp://radiopaedia.org/articles/phaeochromocytomahttp://radiopaedia.org/articles/missing?article%5Btitle%5D=paraspinal+abscesshttp://radiopaedia.org/articles/missing?article%5Btitle%5D=descending+aortic+aneurysmhttp://radiopaedia.org/articles/missing?article%5Btitle%5D=oesophageal+neoplasmhttp://radiopaedia.org/articles/hiatus-herniahttp://radiopaedia.org/articles/bochdalek_herniahttp://radiopaedia.org/articles/lymph-node-enlargementhttp://radiopaedia.org/articles/lymphomahttp://radiopaedia.org/articles/extramedullary-haematopoiesishttp://radiopaedia.org/articles/missing?article%5Btitle%5D=foregut+duplication+cystshttp://radiopaedia.org/articles/neurenteric-cysthttp://radiopaedia.org/articles/oesophageal-duplication-cysthttp://radiopaedia.org/articles/missing?article%5Btitle%5D=thoracic+meningocoelehttp://radiopaedia.org/articles/missing?article%5Btitle%5D=thoracic+meningocoelehttp://radiopaedia.org/articles/oesophageal-duplication-cysthttp://radiopaedia.org/articles/neurenteric-cysthttp://radiopaedia.org/articles/missing?article%5Btitle%5D=foregut+duplication+cystshttp://radiopaedia.org/articles/extramedullary-haematopoiesishttp://radiopaedia.org/articles/lymphomahttp://radiopaedia.org/articles/lymph-node-enlargementhttp://radiopaedia.org/articles/bochdalek_herniahttp://radiopaedia.org/articles/hiatus-herniahttp://radiopaedia.org/articles/missing?article%5Btitle%5D=oesophageal+neoplasmhttp://radiopaedia.org/articles/missing?article%5Btitle%5D=descending+aortic+aneurysmhttp://radiopaedia.org/articles/missing?article%5Btitle%5D=paraspinal+abscesshttp://radiopaedia.org/articles/phaeochromocytomahttp://radiopaedia.org/articles/chordomahttp://radiopaedia.org/articles/ganglioneuromahttp://radiopaedia.org/articles/neuroblastomahttp://radiopaedia.org/articles/neuroblastic-tumourshttp://radiopaedia.org/articles/malignant-peripheral-nerve-sheath-tumourhttp://radiopaedia.org/articles/neurofibromahttp://radiopaedia.org/articles/schwannomahttp://radiopaedia.org/articles/neurogenic-tumours


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The differential diagnosis for an anterior mediastinal mass includes:

thymus

thymoma : most common primary neoplasm of the anterosuperior mediastinum

invasive thymoma

thymic carcinoma

thymolipoma / thymoliposarcoma

thymic cyst

benign thymic hyperplasia

thymic carcinoid

thyroid and parathyroid

thyroid neoplasms

thyroid goitre

parathyroid neoplasms

lymphoma Hodgkin lymphoma

non-Hodgkin lymphoma (NHL)

germ cell tumours

mediastinal teratoma

mature : 75% of mediastinal germ cell tumours

immature

teratocarcinoma (malignant teratoma) mediastinal seminoma

mediastinal embryonal cell carcinoma

mediastinal yolk sac tumour

mediastinal choriocarcinoma

mediastinal mixed cell type germ cell tumour

thoracic aortic aneurysm
http://radiopaedia.org/articles/thymushttp://radiopaedia.org/articles/thymic-epithelial-tumourshttp://radiopaedia.org/articles/invasive-thymomahttp://radiopaedia.org/articles/thymic-carcinomahttp://radiopaedia.org/articles/thymolipomahttp://radiopaedia.org/articles/missing?article%5Btitle%5D=thymoliposarcomahttp://radiopaedia.org/articles/thymic-cysthttp://radiopaedia.org/articles/missing?article%5Btitle%5D=benign+thymic+hyperplasiahttp://radiopaedia.org/articles/thymic-carcinoidhttp://radiopaedia.org/articles/thyroid-glandhttp://radiopaedia.org/articles/missing?article%5Btitle%5D=parathyroid+glandshttp://radiopaedia.org/articles/assessment-of-thyroid-lesionshttp://radiopaedia.org/articles/missing?article%5Btitle%5D=thyroid+goitrehttp://radiopaedia.org/articles/missing?article%5Btitle%5D=parathyroid+neoplasmshttp://radiopaedia.org/articles/lymphomahttp://radiopaedia.org/articles/hodgkin-lymphomahttp://radiopaedia.org/articles/missing?article%5Btitle%5D=NHLhttp://radiopaedia.org/articles/mediastinal-germ-cell-tumourshttp://radiopaedia.org/articles/mediastinal-teratomahttp://radiopaedia.org/articles/missing?article%5Btitle%5D=teratocarcinomahttp://radiopaedia.org/articles/seminomahttp://radiopaedia.org/articles/missing?article%5Btitle%5D=Embryonal+cell+carcinomahttp://radiopaedia.org/articles/missing?article%5Btitle%5D=Yolk+sac+tumourhttp://radiopaedia.org/articles/choriocarcinomahttp://radiopaedia.org/articles/thoracic-aortic-aneurysmhttp://radiopaedia.org/articles/thoracic-aortic-aneurysmhttp://radiopaedia.org/articles/choriocarcinomahttp://radiopaedia.org/articles/missing?article%5Btitle%5D=Yolk+sac+tumourhttp://radiopaedia.org/articles/missing?article%5Btitle%5D=Embryonal+cell+carcinomahttp://radiopaedia.org/articles/seminomahttp://radiopaedia.org/articles/missing?article%5Btitle%5D=teratocarcinomahttp://radiopaedia.org/articles/mediastinal-teratomahttp://radiopaedia.org/articles/mediastinal-germ-cell-tumourshttp://radiopaedia.org/articles/missing?article%5Btitle%5D=NHLhttp://radiopaedia.org/articles/missing?article%5Btitle%5D=NHLhttp://radiopaedia.org/articles/missing?article%5Btitle%5D=NHLhttp://radiopaedia.org/articles/hodgkin-lymphomahttp://radiopaedia.org/articles/lymphomahttp://radiopaedia.org/articles/missing?article%5Btitle%5D=parathyroid+neoplasmshttp://radiopaedia.org/articles/missing?article%5Btitle%5D=thyroid+goitrehttp://radiopaedia.org/articles/assessment-of-thyroid-lesionshttp://radiopaedia.org/articles/missing?article%5Btitle%5D=parathyroid+glandshttp://radiopaedia.org/articles/thyroid-glandhttp://radiopaedia.org/articles/thymic-carcinoidhttp://radiopaedia.org/articles/missing?article%5Btitle%5D=benign+thymic+hyperplasiahttp://radiopaedia.org/articles/thymic-cysthttp://radiopaedia.org/articles/missing?article%5Btitle%5D=thymoliposarcomahttp://radiopaedia.org/articles/thymolipomahttp://radiopaedia.org/articles/thymic-carcinomahttp://radiopaedia.org/articles/invasive-thymomahttp://radiopaedia.org/articles/thymic-epithelial-tumourshttp://radiopaedia.org/articles/thymus


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Epidemiology

The condition can potentially present at any

age but typically presents in the 3rd to 4th

decades.


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Pathology

The disease is of unknown etiology but the

most widely accepted theory is that

Castleman's disease is a chronic low-grade

inflammatory process. The disease is characterised by

hypervascular lymphoid hyperplasia. There

are two distinct sub-types of Castleman

disease : uni-centric (UCD) and multi-centric(MCD). Uni-centric disease is more common


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There are also two recognised sub types

based on histology 1,2

hyaline vascular:

commoner ~ 90%

more uni-centric

plasma cell :

often multi-centric less enhancing

may be more symptomatic 5


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Location

The distribution is as follows :

thorax : ~ 70 %

abdomen / pelvis and retroperitoneum : ~ 10 -

15 %

neck : 10 - 15 %


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Types of CD

Unicentric vs. Multicentric

Hyaline vascular vs. Plasmacytic vs.

Mixed cellularity variety based on

histopathology HIV associated vs not


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Multi-centric disease may involve all of the

above, and is associated with a more

complex clinical course and poorer prognosis.


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Associations

POEMS syndrome

osteosclerotic myeloma

Kaposi sarcoma

AIDS - espacially multicentric 9

amyloidosis10
http://radiopaedia.org/articles/poems-syndromehttp://radiopaedia.org/articles/missing?article%5Btitle%5D=osteosclerotic+myelomahttp://radiopaedia.org/articles/kaposi-sarcomahttp://radiopaedia.org/articles/hiv-aids-1http://radiopaedia.org/articles/amyloidosishttp://radiopaedia.org/articles/amyloidosishttp://radiopaedia.org/articles/hiv-aids-1http://radiopaedia.org/articles/kaposi-sarcomahttp://radiopaedia.org/articles/missing?article%5Btitle%5D=osteosclerotic+myelomahttp://radiopaedia.org/articles/poems-syndrome


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A number of tests can help your doctor determine if

you have Castleman disease, although unicentric

Castleman disease may be found incidentally. People

with unicentric Castleman disease often notice no

symptoms, and the diseased lymph node is foundduring screening or treatment for another illness,

such as during a CT scan or during abdominal or

chest surgery.

Tests your doctor may conduct to diagnose eitherunicentric or multicentric Castleman disease include:

.


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Physical examination

. Your doctor may examine not only your

swollen lymph nodes but also your other

lymph nodes to determine their size and

consistency.


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Radiographic features

CT


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Blood and urine tests

. Blood and urine tests may help your doctor

rule out other infections or diseases. They

can also reveal anemia and abnormalities in

blood proteins that are sometimescharacteristic of Castleman disease.


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Imaging techniques

. An X-ray, computerized tomography (CT)

scan or magnetic resonance imaging (MRI)

scan of your chest, neck, abdomen and pelvis

may detect the presence and number ofenlarged lymph nodes. These tests can also

determine whether organs, such as your liver

or spleen, are enlarged. Positron emission

tomography (PET) scans also may be used indiagnosing Castleman disease and later, to

assess whether a treatment is working


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Lymph node biopsy.

To differentiate Castleman disease from other

types of lymphatic tissue disorders, such as

lymphoma.

For mediastinal lesions : CT


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For mediastinal lesions : CTchest

commonly seen as a mediastinal mass and

rarely as matted lymphadenopathy (with or

without a dominant mass) in a single

mediastinal compartment typical arborising calcification may be seen

within the mass

typically shows intense homogeneous

enhancement following contrast

dynamic CT demonstrates early rapid

enhancement with washout in the delayed

phase

For abdominal lesions : CT
http://radiopaedia.org/articles/castleman-diseasehttp://radiopaedia.org/articles/castleman-disease


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For abdominal lesions : CTabdomen

most commonly, a single well defined

abdominal mass

location is variable, and includes

retroperitoneum, mesentery and porta hepatis3

enhancement is homogeneous, or in larger

lesions ( > 5cm) may demonstrate central

hypo-attenuation consistent with necrosis.

variable pattern of calcification, including

arborising calcification.

For multi centric disease :


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For multi-centric disease :multi-region CT

bilateral hilar and mediastinal

lymphadenopathy

centrilobular nodules

diffuse abdominal lymphadenopathy

hepatosplenomegaly

ascites


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MRI

General signal characteristics include

T1 : iso to hyper intense relative to skeletal

muscle

T1 C+ (Gd) : shows enhancement

T2 : arborsing calcification may be seen as

low signal


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FDG - PET

There is some evidence that Castleman

disease is FDG avid, and therefore 18F-FDG

PET may be useful in identifying the extent of

multi-centric disease and for monitoringdisease progression 7.


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Unicentric CD

More common

Presents as slow growing solitary masstypically located in the mediastinium or

mesenteries. No constitutional sm-s

Not associated with progression tomalignancy

Treated by surgical resection with excellentresults


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Unicentric CD

Histologicaly Unicentric CD is of hyaline

vascular variety


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Multicentric CD

Median age 50-60s ( younger if HIV+)

Widespread lymphadenopathy

Hepatosplenomegaly

Can present with systemic sm-s: fatigue,

fever, wt loss, night sweats (overproduction of

IL-6).

Severe peripheral edema, anemia,hypoalbumenia, peripheral neuropathy


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Multicentric CD

Also can be associated with

autoimmune hemolytic anemia

multiple myeloma

amyloidoisis

Pemphigus

POEMS


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Multicentric CD

Diagnosis by biopsy: Histologicaly usually of

the plasmacytic type or mixed cellularity

variety


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Prognosis of Multicentric CD

rapidly progressive form can lead to death

within weeks (commonly in HIV+)

Chronic persistent form with relapses is more

common


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HIV association

More likely to be associated with Multicentric

Castlemans Disease

More likely to be caused by HHV8

Associated with poor prognosis andprogression to malignancy

Initiation of HAART may lead to fulminant

multicentric CD


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HHV-8 Role

Kaposi's sarcoma-associated herpesvirus also knownas HHV-8

HHV-8 is universally found in HIV+ MCD (but only in40-50% of HIV- MCD)

HHV-8 viral load corresponds to the presence ofsymptoms in CD

HHV-8-infected immunoblasts are highly proliferativeand may coalesce to form "microlymphomas," ordevelop into frank lymphoma


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IL-6 Role

Possible link between overexpression of IL-6

to the systemic manifestations of CD

HHV-8 expresses a viral IL-6 gene (vIL-6)

that activates IL-6 receptor This can induce proliferation of human

myeloma cell lines


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Associated Malignancies

Kaposi's sarcoma (up to 70% in

HIV+/HHV+)

Non-Hodgkin's lymphoma (15-20% of pt)

Hodgkin's lymphoma (both MCD & UCD)

POEMS syndrome (polyneuropathy,

organomegaly, endocrinopathy, monoclonal

gammopathy, and skin changes)


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Treatment and prognosis

For unicentric Castleman disease treatment

is surgical, with good prognosis (can be

curative).

Multicentric Castleman disease may betreated with any combination of surgery,

chemotherapy and prednisolone 6. Prognosis

is relatively poorer.
http://radiopaedia.org/articles/castleman-diseasehttp://radiopaedia.org/articles/castleman-disease


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25-year-old asymptomatic man with right posterior

mediastinal hyaline-vascular Castleman's disease.


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60-year-old woman with thoracic plasma cell

Castleman's disease who presented with chest

tightness.


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32-year-old man with anterior mediastinal hyaline-

vascular Castleman's disease who presented with

anterior chest pain.

26-year-old asymptomatic woman with hyaline-vascular Castleman's


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26-year-old asymptomatic woman with hyaline-vascular Castleman s

disease in right major fissure incidentally found on chest

radiographs; interlobar pleural mass with prominent vessels on

lesion surface and marked adhesion to adjacent lung tissues were

noted during surgery.


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32-year-old asymptomatic woman with pericardial


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y y p phyaline-vascular Castleman's disease incidentally

found on chest radiographs; ovoid mass embedded

within proliferated pericardial fat adjacent to right

atrium was confirmed during surgery.


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Therapy for Multicentric CD

Steroids (15-20% eff, not in HIV+)

IV Ig

Antivirals (acylovir/gancyclovir/foscarnet) in HIVand

HHV8 + population

Rituximab (complete remission in few cases)

CHOP or CVAD (90% eff)

Anti-IL6 or anti-IL6 receptor antibody.

Thalidomide (anecdotal)

11.28.07 castleman's doutova

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