Lymph nodes & spleen, nonlymphoid
Lymph nodes-inflammatory disorders
Castleman disease
Author: Jayalakshmi Balakrishna, M.D.
Topic Completed: 27 September 2017
Minor changes: 6 August 2020
Revised: 30 January 2019, last major update September 2017
Copyright: 2002-2020, PathologyOutlines.com, Inc.
PubMed Search: Castleman disease[title] lymph nodes
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology / etiology | Clinical features | Diagnosis | Laboratory | Radiology description | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Molecular / cytogenetics description | Differential diagnosis | Additional references | Board review style question #1 | Board review answer #1Cite this page: Balakrishna, J. Castleman disease. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lymphnodescastleman.html. Accessed August 8th, 2020.
Definition / general
- Unusual nonmalignant lymphoproliferative disorder
- Can be unicentric or multicentric
- Most often involves lymph nodes but extranodal sites can also be affected
- Three histological subtypes: hyaline vascular type, plasma cell type and mixed hyaline vascular plasma cell
Essential features
- Polyclonal proliferation of B lymphocytes
- Unicentric or multicentric types
- Hyaline vascular or plasma cell morphology types
Terminology
- Angiofollicular hyperplasia
- Giant lymph node hyperplasia
ICD coding
Epidemiology
- Unicentric Castleman disease can affect all age groups and shows no predilection for either gender
- Multicentric Castleman disease affects mainly HIV positive individuals; however, HIV negative individuals can also be affected
- Most cases are KSHV / HHV8 associated
Sites
- Unicentric Castleman disease most commonly affects mediastinum; extrathoracic sites are also involved
- Presents as a solitary lymph node mass
- Multicentric disease affects multiple lymph node sites, predominantly in the cervical region
Pathophysiology / etiology
- Etiology remains unclear
- Current concept is that it is an inflammatory response to an antigenic stimulus; increased production of IL6 is associated with Castleman disease
- Multicentric Castleman disease in HIV infected individuals is caused by HHV8 infection
Clinical features
- Hyaline vascular unicentric Castleman disease presents as a solitary mass
- Plasma cell unicentric Castleman disease presents with a solitary mass and systemic symptoms, including fever, night sweats, fatigue, weight loss, splenomegaly, anemia and hypergammaglobulinemia
- Multicentric Castleman disease is multifocal and is associated with systemic symptoms, such as fever, night sweats, fatigue, cachexia, lymphadenopathy, splenomegaly, cytopenia and hypoalbuminemia, which are often severe
Diagnosis
- Biopsy and histopathological examination is the diagnostic modality of choice
Laboratory
- Plastma cell unicentric Castleman disease may show laboratory abnormalities, such as anemia and hypergammaglobulinemia
- Multicentric Castleman disease is associated with cytopenias and hypoalbuminemia
Radiology description
- Varies by site
- Enlarged lymph nodes or organomegaly are identified by imaging techniques
Case reports
- 12 year old girl with slowly growing mass in the right submandibular salivary gland area (J Oral Maxillofac Surg 2017;75:763)
- 15 year old boy with glycogen storage disease type IA and Castleman disease (Pediatr Blood Cancer 2017;64:e26431)
- 19 year old man with hematuria and a retroperitoneal mass (N Engl J Med 2017;376:684)
- 22 year old woman with isolated mesenteric Castleman disease (J Gastrointestin Liver Dis 2006;15:171)
- 33 year old woman with laparoscopic treatment of abdominal unicentric Castleman disease (BMC Surg 2017;17:38)
- 36 year old woman with generalized body swelling and foamy urine (J Med Case Rep 2017;11:135)
- 55 year old woman with a 1 year history of mass in the posterior hard palate region (J Craniofac Surg 2017;28:e218)
- 58 year old man with fatigue, oliguria, decreased platelets, increased creatinine level, hepatosplenomegaly, ascites, pitting edema and lymph node enlargement (Oxf Med Case Reports 2017;2017:omx021)
- 59 year old man with overlap of IgG4 related disease and multicentric Castleman disease (Intern Med 2017;56:1095)
- 66 year old man with abdominal pain and mass (ACG Case Rep J 2017;4:e71)
Treatment
- Surgical excision is curative for unicentric Castleman disease
- Multicentric Castleman disease needs a more aggressive approach, including systemic chemotherapy or targeted therapies, such as rituximab
Gross description
- Enlarged lymph node
Gross images
Images hosted on other servers:
Tan pink tissue with calcifications
Microscopic (histologic) description
- Hyaline vascular Castleman disease is characterized by prominent vascular proliferation and hyalinization of the vessel walls
- Atretic germinal centers traversed by penetrating vessels are a common finding - lollipop follicles
- Mantle zones are thickened with lymphocytes arranged in layers - onion skin appearance
- Mantle zones may fuse and contain more than one germinal center - twinning
- In the interfollicular areas, there is usually extensive vascular proliferation with perivascular hyalinization
- Follicular dendritic cells may show proliferation and dysplastic features
- Follicular dendritic cell sarcoma has been reported to originate from preexisting hyaline vascular Castleman disease
- Plasma cell unicentric Castleman disease shows aggregates of lymph nodes with sheets of mature plasma cells in the interfollicular areas
- Follicles show hyperplastic germinal centers
- Plasma cells are generally polytypic although rare cases may exhibit monotypic immunoglobulins, predominantly of λ light chain
- Multicentric Castleman disease usually shows a mix of histological features of both plasma cell and hyaline vascular Castleman disease
- KSHV / HHV8 infected cells may show plasmablastic morphology with large nuclei, vesicular chromatin and prominent nucleoli
Microscopic (histologic) images
Scroll to see all images:
Contributed by Jaya Balakrishna, M.D.
HVCD: atrophic follicle
with penetrating vessels
and onion skinning
of mantle zone
HVCD: hyalinized
vessels in
atrophic
follicle center
HVCD: atypical proliferation of follicular dendritic cells
AFIP images
Plasma cell type
Hyaline vascular type
Vascular neoplasm
complicating
hyaline vascular
Castleman disease
Hyaline vascular
Castleman disease
with vascular
hyperplasia
Angiolipomatous
hamartoma in
association with
Castleman disease
Contributed by Jackie D. Sublett II, M.D.
Onion skin pattern
Case #93, low / medium power
Figure 1
Figure 2
Figure 3
Low power targetoid pattern
Lollipop appearance
Onion skin pattern of lymphocytes
High power:
Figure 4
Figure 5
Images hosted on other servers:
Hyaline vascular variant:
Probable early lesion: lymphocyte cuff surrounds a pale central area of concentric hyalinized cells and a small vessel penetrates the cuff and enters the central area
Cuff of lymphocytes surrounds thick walled vessel
Various images
Follicle has two
pale centers, one
irregular; vessel
enters from below
Almost total obliteration of subcapsular sinus
Center of follicle has prominent vessel
Onion skin pattern of
lymphocytes with abnormal
vasculature and multinucleated
follicular dendritic cells
Reticulin stain shows profusion of small vessels
Extensive proliferation of
small, thick walled
vessels with prominent
endothelial cells
With Kaposi sarcoma in
HIV negative patient
receiving cyclosporine A for
minimal change nephropathy
Fig 1: follicular hyperplasia with concentric mantle zones
2: interfollicular zones have prominent vascular proliferation
3: targetoid lymphocytes in mantle zone of hyalinized follicles with an occasional capillary penetrating radially into the germinal centers
Fig 1: CT scan; 2: 7 cm tumor with rib and vertebrae; 3: scrape shows cellular material with discohesive cells containing high N/C ratios; 4: H&E shows expanded mantle zone with small lymphocytes arranged in concentric layers
Plasma cell and plasmablastic variants:
Interfollicular
space shows
numerous mature
plasma cells
Plasmablastic and plasma cell variant
Positive stains
- Immunohistochemcial stains highlight the overall architecture of the lymph nodes
- Viral IL6 highlights the HHV8 positive cells
- KSHV / HHV8 positive cells are positive for OCT2, BLIMP1 and IRF4 / MUM1 and are negative for PAX5, BCL6 and CD138
- They contain cytoplasmic IgM with monotypic λ light chain
Molecular / cytogenetics description
- Polyclonal B cells, even in cases with monotypic light chain expression
Differential diagnosis
- In HHV8 positive cases, HHV8 associated lymphoproliferative disorders should be ruled out
- Other reactive causes of lymph node enlargement and lymphoproliferative disorders should be ruled out
Additional references
Board review style question #1
All the following are features of hyaline vascular type of Castleman disease, except:
- Follicular atrophy
- Onion skinning of mantle zones
- Penetrating vessels in the germinal centers
- Plasma cell infiltrates
Board review answer #1
D. Plasma cell infiltrates. All are features of hyaline vascular Castleman disease, including atrophic follicles, penetrating vessels, onion skinning of mantle zones and hyalinized vessels. Plasma cell accumulation in the interfollicular areas is a feature of plasma cell variant.
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Reference: Castleman disease
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Reference: Castleman disease
