A 47-year-old man with a history of lung nodules was found to have an incidental exophytic mass (4.6 cm) arising from the upper pole of the left kidney on a CT scan of the abdomen in 2017; it increased in size to 5.9 cm in 2019 and to 11.6x8.3x5.7 cm in 2020.
What is the diagnosis of this renal neoplasm?
a. Malignant PEComa
b. Clear cell renal cell carcinoma with sarcomatoid transformation
c. Chromophobe renal cell carcinoma
d. Melanoma
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Answer to July/August's Case of the Month.
D. Multicentric Castleman disease
Sections demonstrate overall preserved lymph node architecture with prominent interfollicular vascularity and secondary follicles that show involution and variable hyalinization of germinal centers with prominent mantle zones (image 1). Plasma cells and plasmablastic cells are increased in the interfollicular region and mantle zones (image 2). The plasmablasts show stippled nuclear staining for HHV8 (image 3) and cytoplasmic staining for IgM (image 4).
Multicentric Castleman disease is a systemic lymphoproliferative disease that occurs in patients with immunodeficiency or immunodysregulation. It has multiple sites of involvement and patients typically present with diffuse lymphadenopathy, splenomegaly, and systemic symptoms (such as fever, fatigue, or weight loss). In HIV-positive patients, MCD is almost always associated with human herpesvirus type 8 (HHV8) infection. HHV8 encodes for a homolog of human interleukin 6 (IL-6) that regulates differentiation of B lymphocytes into plasma cells, which explains the abundance of plasma cells and plasmablasts. Plasmablasts in MCD are characteristically positive for IgM and show lambda light chain restriction. HHV8 LANA1 immunostain is strongly positive; EBER in situ hybridization for Epstein Barr virus is negative. A subset of MCD cases are HHV8-negative and can be associated with neuropathy, organomegaly, endocrinopathy, monoclonal M-protein, and skin lesions – POEMS syndrome (1).
The abundance of lymphoid follicles raises differential diagnoses of reactive follicular hyperplasia and follicular lymphoma. Reactive lymphoid hyperplasia demonstrates numerous enlarged follicles with reactive-appearing germinal centers and frequent tingible-body macrophages (2). Follicular lymphoma can present with involuted germinal centers, but usually does not have plasmacytosis. Immunohistochemical stains can help confirm the neoplastic nature of germinal centers, which are usually positive for CD10 and BCL6 with coexpression of BCL2 (3). Morphologic findings in the lymph node raise the differential diagnosis of other types of Castleman disease: hyaline vascular and unicentric plasma cell variants. All variants of Castleman disease show regressed follicles with varying degrees of hyalinization and increased interfollicular vascularity. These changes are very prominent in the hyaline vascular variant. The plasma cell variant typically demonstrates marked interfollicular plasmacytosis and shows morphologic overlap with MCD; however, it is by definition localized (unicentric) and HHV8-negative.
Submitted by Anna Shestakova, Hematopathology fellow, University of Michigan, Ann Arbor, Michigan, USA.
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References
- A Dispenzieri, DC Fajgenbaum, “Overview of Castleman disease,” Blood, 135, 1353 (2020). PMID: 32106302.
- LM Weiss, D O’Malley, “Benign lymphadenopathies,” Mod Pathol, 26, S88 (2013). PMID: 23281438.
- S Swerdlow et al., WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC Press: 2017.
