Morpho-immunophenotypic diversity of Castleman's disease, hyaline-vascular type: With emphasis on a stroma-rich variant and a new pathogenetic hypothesis

Abstract

A histologic review of 102 cases of Castleman's disease of the hyaline-vascular type, with a detailed paraffin immunophenotypic study of 23 of them, was undertaken to evaluate the morphologic variability of this disorder and its immuno/cyto-architectural characteristics. All cases had features in common including: abnormal follicles, with increased vascularity, poorly formed germinal centers and predominance of the mantle zone; lack of sinuses; and hypervascular interfollicular tissue containing large numbers of KP1-positive plasmacytoid monocytes. Networks of actin-positive cells [fibroblastic reticulum cells (RCs) or "myoid cells"] and KP1-positive dendritic cells (histiocytic RCs) were seen. There were differences in the proportion of follicles to interfollicular tissue, which covered a continuum from a "follicular", through a "classic", to a "stroma-rich" variant. The last-mentioned was qualitatively different as it showed loss of HECA-452 and MECA-79 reactivity in the blood vessels, decreased plasmacytoid monocytes and increased myoid cells and histiocytic RCs. In 5 cases there was formation of distinct nodular growths which varied from spindle cell foci to angio-histiocytic-RC proliferations, all of which may be confused with vascular or follicular dendritic RC neoplasms. From our findings, data from the literature and the working hypothesis that plasmacytoid monocytes are the precursors of both follicular dendritic RCs and sinus lining cells (Parwaresch et al.), a pathogenetic theory is proposed for this type of Castleman's disease which postulates that a developmental block in plasmacytoid monocytes results in their accumulation with poor formation of germinal centers and sinuses under stimulation. The lack of sinuses would lead to impaired egress of circulating lymphocytes which, however, would continue to enter the node through functional high endothelial venules and to accumulate in the mantle zone. The factors responsible for angiogenesis and for the cellular growths that characterize the stroma-rich variant remain to be determined, as do the relationships between the three variants.

Monoclonality and cytogenetic abnormalities in hyaline vascular Castleman disease

“…The diagnosis was reviewed by three hematopathologists and the hyaline vascular Castleman disease cases were further subclassified as classical, lymphoid, 8 and stromal-rich variant. 9,11 The classical cases of hyaline vascular Castleman disease showed regressed and confluent follicles with radially penetrating sclerotic arterioles ('lollipop lesion'), hyaline deposits in germinal centers, concentric layering of mantle zone lymphocytes ('onion skin appearance'), inapparent sinuses, and interfollicular vascular hyperplasia (Figures 1a and b). The lymphoid variant was characterized by mantle zone expansion around the atrophic, inconspicuous germinal center that may mimic follicular lymphoma or mantle cell lymphoma (Figure 1c).…”

“…The stromal-rich variant was defined as a prominent interfollicular zone occupying 50% or more of the nodal area. 11 The interfollicular zones had increased stromal cells and blood vessels and were associated with residual lymphoid follicles (Figure 1d). The frequent components of stromal cells were actinpositive 'myoid' cells and follicular dendritic cells.…”

“…10 Although stromal overgrowth is usually considered secondary, several authors have stressed the possible pathogenetic role of dysplastic follicular dendritic cells in this disorder. [11][12][13] Furthermore, there are emerging data demonstrating clonal cytogenetic abnormalities in stromal cells of hyaline vascular Castleman disease without overt stromal cell overgrowth. Pauwels et al 14 reported a case of hyaline vascular Castleman disease with dysplastic follicular dendritic cells associated with a clonal t(1;16)(p11; p11).…”

Intrapulmonary Castleman’s Disease Pretending to Be a Lung Cancer—Work Up of an Intrapulmonary Tumour

“…The localized type of the disease presents with a slow growing, progressive and painless lymph node enlargement and is situated cervical (42%), mediastinal (31%), abdominal (18%) and retroperitoneal (5%). 7) Other authors reported that the majority of CD is detected mediastinal (46%-70%), only 3%-39% intraabdominal and 10%-15% is seen in the periphery. 8) These differences are due to different diagnostic algorithms and to the low incidence of the disease.…”

“…The cause of CD is unknown; it is discussed that the localized type is started by an antigen stimulus of an abnormal plasmacytoid monocyte population in a lymph node. 7) The multicentric form is believed to be induced by chronic infection. The treatment of choice for the localized form of CD is complete surgical resection including systematic lymph node dissection, resulting in cure in all reported cases.…”