STEP 1:
Grading

TYPICAL HISTOPATHOLOGICAL CONSTELLATIONS SEEN IN iMCD

One group of cases (n = 29) showed regressed germinal centres (GCs), follicular dendritic cell (FDC) prominence, hypervascularization 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 hypervascularization 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”.