Co-Existence of Multicentric Castleman's Disease and Kaposi's Sarcoma.

Castleman's disease (CD) or giant lymph node hyperplasia is a rare disorder that can be unicentric or multicentric. Multicentric Castleman's disease (MCD) is manifested by generalized lymphadenopathy, hepatosplenomegaly, polyclonal hypergammaglobulinemia, hematological abnormality, and constitutional symptoms. Human herpesvirus 8 (HHV-8) infection is present in nearly 100% MCD associated with HIV-1 infection, but in about 50% of cases of HIV negative. Herein, we report a 77-year-old man with systemic involvement and skin lesions on the anterior aspect of both legs in the previous site of saphenous vein angioplasty. Co-existence of MCD with Kaposi's sarcoma (KS) led us to present this rare case.

What was known?

Multicentric Castleman's disease (MCD) is an uncommon disease and approximately 50% of patients are human herpesvirus 8 positive. Co-existence of multicentric Castleman's disease and Kaposi's Sarcoma has been rarely reported in medical literature.

Introduction

Castleman's disease (CD) or giant lymph node hyperplasia is a rare disorder first explained by Castleman et al., in 1954. It can be unicentric or multicentric and mostly involves mediastinum (60%), retroperitoneum (11%), and axilla (4%).[123] Multicentric Castleman's disease (MCD) is manifested by generalized lymphadenopathy, hepatosplenomegaly, and polyclonal hypergammaglobulinemia, high erythrocyte sedimentation rate (ESR), anemia, thrombocytopenia, and constitutional symptoms.[4] Human herpes virus 8 (HHV-8) infection has been identified in nearly 100% of HIV-positive and 50% of HIV-negative MCD patients.[56] This virus predisposes patients to much higher risk of other malignancies, including Kaposi's sarcoma (KS) (13%) and non-Hodgkin's lymphoma (18%).[37] Kaposi's sarcoma is a vascular neoplasm with a compound and unknown histogenesis in which most of the spindle cell lesions express CD31 and CD34.[6] Both cutaneous and nodal forms of KS have been documented in MCD.[8] Castleman's disease is histologically divided into three types: Hyaline vascular type or angiofollicular type, plasma cell (PC) type, and mixed type.[9]

Co-incidence of MCD with KS and some common features of them led us to report this case. It is unknown whether KS is a consequence of immunosuppression caused by MCD or KS is a clinical feature of MCD.

Case Report

A 77-year-old man was admitted to our dermatology clinic with fever, anorexia, weight loss, generalized pruritus, and multiple cutaneous lesions on the legs. The patient's complaints started 1 year ago; however, the legs’ edema was developed during the recent 6 months. A physical examination revealed cachexia, pallor, xerosis with excoriation marks, skin lesions, and generalized lymphadenopathy. The lymph nodes were discrete, mobile, firm, and non-tender ranging in size from 0.5 to 6 cm. Cutaneous lesions were violaceous indurated papules and plaques on the anterior aspects of both legs in the previous site of saphenous vein angioplasty from 3 years ago. These lesions clinically resembled KS [Figures 1 and 2]. Additionally, laboratory findings showed anemia (Hb: 9.6 mg/dl), increased ESR (98 mm/h), elevated WBC count (11100 mm3) with 12% eosinophilia, and also negative viral markers (HHV-8, HIV, HCV, HBV). Notably, chest CT scan demonstrated extensive bilateral axillary adenopathy, pretracheal and antrosuperior mediastinal adenopathy, subpleural wedge-shaped consolidation on the base of the left lung, and subpleural nodules on the right lung recommended to rule out of lymphoma. Abdominopelvic ultrasound revealed mild hepatosplenomegaly with a hyperechoic solid mass in the mid portion of spleen suggesting hemangioma whereas retroperitoneal lymphadenophathy was not detected. Also, bone marrow aspiration was normal.

Figure 1

Brown-bluish papules and nodules of Kaposi's sarcoma

Figure 2

Violaceous indurated lesions on the legs in the previous location of saphenous angioplasty

A skin biopsy of the lesions showed hypercellular neoplasm composed of proliferated spindle-shape cells arranged in a whorled and fascicular pattern with slit-like spaces containing red blood cell with extravasation [Figure 3]. An immunohistochemical (IHC) staining for CD34 and CD99 was positive. An axillary lymph node biopsy demonstrated follicular hyperplasia with marked vascular proliferation, hyalinization, and few tight concentric layers of lymphocytes, arranged in onion skin appearance [Figure 4]. The patient was treated with granulocyte colony-stimulating factor (G-CSF) for four sessions, alpha interferon 2b (IFN-α2b) subcutaneously for 5 months and Vinblastin weekly. Eventually, patient's pruritus relieved after 2 months, lymphadenopathy regressed, general condition became good, and also, the patient went into the clinical remission. Moreover, radiotherapy within 5 months and KS lesions regressed. The patient received 30 sessions of irradiation on the skin lesions resulting in complete regression.

Figure 3

Proliferation of spindle cells arranged in a whorled and fascicular pattern with slit-like spaces containing red blood cell extravasation (hematoxylin and eosin×40)

Figure 4

Follicular hyperplasia with prominent vascular proliferation, hyalinization and few tight concentric layers of lymphocytes, arranged in onion skin appearance (hematoxylin and eosin×100)

Discussion

Castleman's disease is divided into localized and multicentric type and histologically, almost the entire multicentric variants are PC type.[2] The standard curative treatment of localized CD is surgical excision with a 5-year survival rate of 100% and excellent prognosis.[3] Additionally, corticosteroids, chemotherapic agents and radiation therapy are the other modalities for the treatment of MCD.[10]

In 2003, Boller et al., reported simultaneous of MCD and KS in a 17-year-old patient after treatment with cyclosporine for nephropathy.[1] In addition, De Rosa et al. described a woman affected by MCD and complicated by KS. They discussed that MCD and KS might be presented in a same immunologically patient or KS was a consequence of immunosuppression.[8]

Our patient shared many similarities to the previous literature reports and demonstrated MCD findings such as fever, anorexia, weight loss, peripheral and mediastinal lymphadenopathy, and also hepatosplenomegaly. He had simultaneously violaceous papules and plaques over both legs and the histopathology findings were consistent with co-existence of MCD and KS. Notably, MCD has been reported in adults usually before age 30[3] and shows an association with HHV-8 and HIV infections.[11] In contrast, our patient was a 77-year-old man and compared with the prior literature findings, he had HHV-8 and HIV-negative serology. Co-incidence of MCD with KS in our case report can be interpreted that MCD may be complicated by KS or the latter is a manifestation of MCD.

Finally, MCD should be kept in mind as a differential diagnosis in a patient with KS.

What is new?

MCD should be kept in mind as a differential diagnosis in a patient with KS.