TYPICAL HISTOPATHOLOGICAL CONSTELLATIONS SEEN IN iMCD
One group of cases (n = 29) showed regressed germinal centres (GCs), follicular dendritic
cell (FDC) prominence,
hypervascularisation with proliferation of high endothelial venules, and patent sinuses. Mantle zones were also
expanded in some cases with “onion skinning,” displayed by concentric rings of small lymphocytes around regressed GCs.
We sometimes observed the “lollipop sign” of prominent blood vessels radially penetrating GCs and “budding” or
“twinning” of follicles, which involves ≥2 GCs located within a single follicle. Historically, many features of this
group would be described as consistent with the “hyaline vascular” (HV) histopathologic subtype of multicentric
Castleman Disease (MCD). However, many hematopathologists consider HV to only occur in Unicentric Castleman Disease
(UCD) based on the classic descriptions by Benjamin Castleman, and a few HV-UCD features, such as FDC dysplasia and
sclerotic vessels, are not often observed in MCD.
Recently, many HV features have been described in iMCD patients with TAFRO syndrome. To avoid confusion, we voted to
consider iMCD patients
with this constellation of HV-like histopathologic features, including regressed GCs and hypervascularisation without
plasmacytosis,
as having the “hypervascular” (HyperV) histopathologic subtype.
Of note, most iMCD cases with TAFRO clinical features from our study and the literature demonstrated HyperV or mixed
histopathology,
but some cases did not. Also, we observed iMCD patients with HyperV or mixed histopathology that did not have the
TAFRO clinical syndrome.
On the other end of the spectrum were patients (n = 23) with sheetlike plasmacytosis and
increased numbers of
follicles with large hyperplastic GCs. These cases, which represent the “plasmacytic” (PC) subtype of iMCD, also have
occasional regressed GCs and mild vascularity. A subset of cases (n = 19) demonstrated
histologic features that were
intermediate between the HyperV and PC subtypes with regressed lymphoid follicles and plasmacytosis, which were
considered “mixed”.
Abbreviations
FDC, follicular dendritic cell; GCs, germinal centres; HV, hyaline vascular; HyperV, hypervascular; iMCD,
idiopathic Multicentric Castleman Disease; MCD, Multicentric Castleman Disease; PC, plasmacytic; TAFRO,
thrombocytopenia, anasarca, fever, reticulin myelofibrosis, organomegaly; UCD, Unicentric Castleman Disease.
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Case studies