**4. Clinical features and management**

associated with elevated levels of IL-6 [15,16]. Increased VEGF expression is also noted in CD and is likely to be responsible for the increased angiogenesis component of the disease [19].

**Figure 3.** Human Herpesvirus-8 immunohistochemical stain showing mantle zone concentricity and distinct HHV-8

positive nuclear staining of lymphoid cells in the mantle zone (100× magnification)

**Figure 2.** Haematoxylin and Eosin stained section of lymph node (200× magnification) showing the radially penetrat‐

ing blood vessels transfixing the germinal centre – 'lollipop' appearance

250 Immunopathology and Immunomodulation

Two distinct clinical variants of Castleman's disease are recognised: MCD and UCD. Unicen‐ tric Castleman's disease (UCD) refers to localized disease, presenting at a single site, such as the chest (most commonly the mediastinum), neck, abdomen, or other sites. Typically patients are asymptomatic and come to clinical attention when an enlarged lymph node is noted on physical examination or at imaging studies [1,2, 23].

Figure 4. Bar graph which depicts the number of patients seen with Castleman's disease at Chris Hani Baragwanath Academic Hospital from 1990 to 2014 **Figure 4.** Bar graph which depicts the number of patients seen with Castleman's disease at Chris Hani Baragwanath Academic Hospital from 1990 to 2014

At Chris Hani Baragwanath Academic Hospital (CHBAH), Soweto, Johannesburg, a total of 38 patients were seen with CD over a 25-year period. Three of the patients (7.9%) were diagnosed with UCD and 35 (92.1%) with MCD. Of all the patients with CD, 22/38 (57.9%) were seen in the last 5 years compared to 42.1% in the first 20 years. The increase in the number of patients with CD in the last 5 years is primarily as the result of the ongoing HIV pandemic in South Africa and the contribution from HIV. Ninety five percent (21/22) of the patients seen in the last five years and 100%

Anaemia (A) or

thrombocytopenia (T) Treatment HIV Response Outcome

resection Negative Complete

resection Negative Complete

resection Negative Complete

response Alive

response Alive

response Alive

of those with MCD were HIV seropositive.

adenopathy

Age Gender Site of lymph-

Table 1. Clinical characteristics of Unicentric Castleman's disease

Localised or systemic disease

1 18 M Mediastinum Localised No A or T Surgical

2 64 F Inguino-femoral Localised No A or T Surgical

3 59 F Axilla Localised No A or T Surgical

7

Multicentric Castleman's disease (MCD) refers to a systemic disease with constitutional symptoms (fever, night sweats, weight loss), generalized lymphadenopathy and hepatosple‐ nomegaly. It is usually associated pathologically with the plasma cell or mixed variant. Unlike UCD, MCD is strongly associated with HIV, immunosuppression and HHV-8 [11,23,24]. Laboratory studies usually reveal the presence of anaemia, a raised ESR, elevated CRP, thrombocytopenia, hypoalbuminemia and polyclonal hypergammaglobulinemia [3, 4,11,15].

At Chris Hani Baragwanath Academic Hospital (CHBAH), Soweto, Johannesburg, a total of 38 patients were seen with CD over a 25-year period. Three of the patients (7.9%) were diagnosed with UCD and 35 (92.1%) with MCD. Of all the patients with CD, 22/38 (57.9%) were seen in the last 5 years compared to 42.1% in the first 20 years. The increase in the number of patients with CD in the last 5 years is primarily as the result of the ongoing HIV pandemic in South Africa and the contribution from HIV. Ninety five percent (21/22) of the patients seen in the last five years and 100% of those with MCD were HIV seropositive.


**Table 1.** Clinical characteristics of Unicentric Castleman's disease

With regard to UCD, there were 2 females and 1 male, with a female to male ratio of 2:1. The mean age at presentation was 47 years. All the patients were diagnosed post biopsy/resection of localised nodal disease. None of the patients were HIV seropositive. No further treatment was required in these patients after the initial surgical resection. All the patients are alive and are well on observation (see Table 1).

A summary of the clinical characteristics of the patients with MCD is depicted in Table 2.



**Table 2.** Summary of the clinical characteristics of Multicentric Castleman's disease

## **5. Associations**

Multicentric Castleman's disease (MCD) refers to a systemic disease with constitutional symptoms (fever, night sweats, weight loss), generalized lymphadenopathy and hepatosple‐ nomegaly. It is usually associated pathologically with the plasma cell or mixed variant. Unlike UCD, MCD is strongly associated with HIV, immunosuppression and HHV-8 [11,23,24]. Laboratory studies usually reveal the presence of anaemia, a raised ESR, elevated CRP, thrombocytopenia, hypoalbuminemia and polyclonal hypergammaglobulinemia [3, 4,11,15].

At Chris Hani Baragwanath Academic Hospital (CHBAH), Soweto, Johannesburg, a total of 38 patients were seen with CD over a 25-year period. Three of the patients (7.9%) were diagnosed with UCD and 35 (92.1%) with MCD. Of all the patients with CD, 22/38 (57.9%) were seen in the last 5 years compared to 42.1% in the first 20 years. The increase in the number of patients with CD in the last 5 years is primarily as the result of the ongoing HIV pandemic in South Africa and the contribution from HIV. Ninety five percent (21/22) of the patients seen

> **Anaemia (A) or thrombocytopenia**

Localised No A or T Surgical

With regard to UCD, there were 2 females and 1 male, with a female to male ratio of 2:1. The mean age at presentation was 47 years. All the patients were diagnosed post biopsy/resection of localised nodal disease. None of the patients were HIV seropositive. No further treatment was required in these patients after the initial surgical resection. All the patients are alive and

A summary of the clinical characteristics of the patients with MCD is depicted in Table 2.

Median age; Mean age; Range Median = 36 years; Mean = 37years; Range = 18–64 years

Gender; ratio Males = 19, Females = 16; M:F ratio – 1.2:1

**Treatment HIV Response Outcome**

response

response

response

Alive

Alive

Alive

resection Negative Complete

resection Negative Complete

resection Negative Complete

in the last five years and 100% of those with MCD were HIV seropositive.

**(T)**

**Localised or systemic disease**

<sup>1</sup> <sup>18</sup> <sup>M</sup> Mediastinum Localised No A or T Surgical

<sup>3</sup> <sup>59</sup> <sup>F</sup> Axilla Localised No A or T Surgical

**Table 1.** Clinical characteristics of Unicentric Castleman's disease

**Characteristic Result/Finding**

Multicentric disease 35/35 = 100%

Number of patients 35

**Age Gender Site of lymph-**

252 Immunopathology and Immunomodulation

<sup>2</sup> <sup>64</sup> <sup>F</sup> Inguino-

**adenopathy**

femoral

are well on observation (see Table 1).

Castleman's disease may be seen in association with other diseases including POEMS syn‐ drome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein/gammopathy, and skin changes/sclerotic bone lesions), paraneoplastic pemphigus, Kaposi's sarcoma, Hodgkin lymphoma, Non Hodgkin lymphoma (in particular, primary effusion lymphoma (PEL), and diffuse large B-cell lymphoma -DLBCL) [2,11, 22, 25,26,27].
