Unicentric castleman's disease located in the lower extremity: a case report
© Schaefer et al; licensee BioMed Central Ltd. 2011
Received: 19 May 2011
Accepted: 12 August 2011
Published: 12 August 2011
Castleman's disease is a rare form of localized lymph node hyperplasia of uncertain etiology. Although the mediastinum is the most common site of involvement, rare cases occurring in lymph node bearing tissue of other localization have been reported, including only a few intramuscular cases. Unicentric and multicentric Castleman's disease are being distinguished, the latter harboring an unfavorable prognosis.
Here, we present a case of unicentric Castleman's disease in a 37-year-old woman without associated neoplastic, autoimmune or infectious diseases. The lesion was located in the femoral region of the right lower extremity and surgically resected after radiographic workup and excisional biopsy examinations. The tumor comprised lymphoid tissue with numerous germinal centers with central fibrosis, onion-skinning and rich interfollicular vascularization. CD23-positive follicular dendritic cells were detected in the germinal centers and numerous CD138-positive plasma cells in interfollicular areas. The diagnosis of mixed cellularity type Castleman's disease was established and the patient recovered well.
In conclusion, the differential diagnosis of Castleman's disease should be considered when evaluating a sharply demarcated, hypervascularized lymphatic tumor located in the extremities. However, the developmental etiology of Castleman's disease remains to be further examined.
KeywordsCastleman's disease unicentric mixed cellularity type follicular dendritic cells
Castleman's disease is regarded as a polyclonal lymphoid proliferation of unknown etiology, also designated as angiofollicular lymph node hyperplasia . It was first described by Benjamin Castleman in 1954 as "localized mediastinal lymph node hyperplasia resembling thymoma" . The etiology of this uncommon entity is still unclear and only few studies on the molecular and cytogenetic characteristics of this disorder exist [3, 4]. The most common site of involvement is lymph node-bearing tissue with a predilection for the mediastinum (70%), but also occurring in the neck, axilla, pelvis and retroperitoeum . However, a few extranodal cases have been reported in the literature, comprising 9 intramuscular cases . Unicentric Castleman's disease behaves rather benign and can be cured by surgical removal, whereas the multicentric variant harbors the risk of an unfavorable course, and therefore requires an aggressive multimodal chemotherapy [1, 5, 6]. Here, we describe a case of unicentric mixed cellularity type Castleman's disease of the lower extremity. We present the clinico-pathological characteristics with a review of the literature.
Written informed consent was obtained from the patient for publication of this case report and any accompanying images.
Castleman's disease is a rare disorder arising predominantly in young adult patients without a gender predominance . Based on clinical and radiological findings Castleman's disease is classified as unicentric vs. multicentric disorder . Only 9 cases of intramuscular Castleman's disease have been reported with a female predominance (7 women vs. 2 men), occurring between the age of 14 and 48 years . Most of these cases developed in the shoulder girdle with only one case arising in the lower extremity (peroneal muscle) . Here, we present a case of Castleman's disease of the lower extremity with inter-compartmental localization but probable origin in lymph nodes along the femoral artery since the tumor encased the femoral artery and vein. Whether previously described intramuscular cases developed actually from skeletal muscle or from ectopic lymphatic tissue remains to be discussed. In the present case a primary soft tissue tumor was suspected clinically. The establishment of the correct preoperative diagnosis of Castleman's disease by histopathological examination of excisional biopsies is challenging due to the rarity of this entity, especially when the tumor arises in the extremities . Deep biopsy and careful tissue sampling are necessary to render the hyaline vascular parts with lymph follicles with aberrant and shrunken germinal centers with concentric onion skin-like arrangement of lymphocytes and "lollipop" formations suggestive of Castleman's disease . Additionally, the characteristic hypervascularization causes homogeneous contrast enhancement in MRI and CT imaging . Radiological differential diagnoses include vascular tumors, extrapleural solitary fibrous tumors, malignant lymphoma, soft tissue sarcoma and metastases .
Clinico-pathological characteristics of different subtypes of Castleman's disease as described in previous studies1-10 and the present case
F = M, young adults
Abnormal follicles with shrunken germinal centers consisting of FDC, "onion skinning", vascular ingrowth: "lollipop" formations, interfollicular hypervasculariza-tion
FDC: CD21, CD35, EGFR
Nephrotic syndrome, mixed connective tissue disorder, Hodgkin disease
F = M, young adults
Hyperplastic germical centers, intact mantle zone infiltrated by mature plasma cells, interfollicular plasmacytosis
Plasma cells: CD138
Elevated IgG4, elevated IL-6; infections: HHV-8, HIV; autoimmune, paraneoplastic and connective tissue diseases
Multimodal approach: radiation, chemo-therapy, and/or surgery
Mixed cellularity (present case)
F, 37 years
A combination of hyaline vascular and plasma cell type
FDC: CD23, KiM4P; Plasma cells: CD138
The developmental etiology of Castleman's disease is still being discussed. In the hyaline vascular type CD5-positive lymphocyte proliferations, possibly stimulated by certain cytokines, have been suggested to play a role in the development of the disease . Some authors even designate this subtype as an "atypical CD5-positive B-cell disorder" whereas others propose a disease of follicular dendritic cells [8, 9]. In our case, CD5-positive B-cells were detected in the periphery of the germinal centers surrounding the follicular dendritic cells. Cytogenetic anomalies detected in stromal cells in hyaline vascular Castleman's disease include t(1;22)(qter;q13) and t(7;8)(q37.3;q12) . Furthermore, rearrangement and partial deletion of the HMGIC gene in follicular dendritic cells due to an unbalanced 6;12 translocation has been reported, suggesting a clonal proliferation of follicular dendritic cells the hyaline vascular subtype . Some reports describe a possible association with the development of angiomyoid proliferative lesions and vascular tumors and a possible mesenchymal tumorigenesis being implicated in hyaline vascular Castleman's disease . An association of the multicentric type with an human herpes virus (HHV)-8 infection in HIV-positive patients has recently been discovered . HIV, other conditions of immune deregulation and primary auto-immune diseases (systemic lupus erythematosus, POEMS syndrome, nephrotic syndrome) may even exhibit histologic findings similar to Castleman's disease, including regressive lymph nodes [5, 8]. Furthermore, excessive production of interleukin-6 in germinal centers of multicentric Castleman's disease has been observed to be associated with an HHV-8 infection and it has been suspected to play an important role in the pathophysiology [5, 7, 10]. However, in the present case no constitutional symptoms or related disorders could be observed as yet.
Although infrequent, it is important to bear the differential diagnosis of Castleman's disease in mind when evaluating a sharply demarcated, hypervascularized lymphatic hyperplasia located in the extremities. The etiology of Castleman's disease remains to be further examined in future studies.
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