The histopathological spectrum of kidney biopsies in patients with thymoma and myasthenia gravis: a report of 24 biopsies from a single institution

Abstract

Background Nephropathy in patients with thymic diseases such as thymoma and myasthenia gravis (MG) is rare and has been described mostly as isolated case reports. Here we evaluate a series of kidney biopsies from patients with thymoma and/or MG from a single institution, in order to better define the spectrum and relative frequencies of thymic disease-associated nephropathies. Methods Case series. A retrospective study of 32,462 native kidney biopsies from January 2005 through December 2019 at Cedars-Sinai Medical Center, Los Angeles, CA. Results Twenty-four biopsy specimens (0.07%) from patients with a history of thymoma and/or MG were identified. Two patients had repeat biopsies. The most common pathologic diagnosis which could be immunologically attributed to thymic disease was minimal change disease (MCD; 45%), followed by tubulointerstitial nephritis (TIN; 14%), immune complex (IC)-mediated glomerulonephritis (9%), membranous nephropathy (5%), and IgA nephropathy (5%). Interestingly, 50% of the MCD and 67% of TIN cases concomitantly showed mild IgG-dominant immune complex deposition in mesangial areas and/or in tubular basement membranes. In the two patients with repeat biopsies, mild mesangial IC deposition developed in MCD but disappeared in the TIN patient with the second biopsy. Pathologic diagnoses unlikely related to the underlying thymic disease were diabetic glomerulosclerosis (9%), acute tubular necrosis (9%), and monoclonal immunoglobulin deposition disease (5%). Conclusion Thymic disease is associated with a wide spectrum of kidney diseases affecting the glomerular and tubulointerstitial compartments, often with low-grade IC deposition. These findings suggest a role of immunologic dysregulation in the pathogenesis of thymic disease-associated nephropathy.

Multi-organ single-cell transcriptomics of immune cells uncovered organ-specific gene expression and functions

“…We found that progenitor cells from the kidney were clustered with classical thymocytes, indicating a thymocyte-like phenotype. This relationship is intriguing given the previous association between thymus and kidney diseases, although the underlying mechanism remains unknown 26 – 28 . Additionally, our findings provide compelling evidence indicating that thymic B cells may indeed originate from the bone marrow 29 .…”

Multi-organ single-cell transcriptomics of immune cells uncovered organ-specific gene expression and functions

“…Interestingly, we found that progenitor cells from the kidney were clustered with classical thymocytes, indicating a thymocyte-like phenotype. This relationship is intriguing given the previous association between thymus and kidney diseases, though the underlying mechanism remains unknown 31,32,33 . Additionally, we found evidence to suggest that thymic B cells originate from the bone marrow, as their transcriptome showed the strongest correlation with bone marrow cells compared to blood and spleen cells 34 .…”

Thymoma with hypercalcemia and membranous nephropathy

“…10 Since 1998, eight cases of thymoma/myasthenia gravis combined with MN have been reported, and more than half of the cases did not demonstrate a direct association between thymoma and MN. [10][11][12][13][14] Hypercalcemia often leads to chronic interstitial nephritis, typically accompanied by low-grade proteinuria, and rarely by nephrotic-range proteinuria. 15 Our patient's proteinuria level continued to increase even after achieving control of blood calcium levels.…”