Diagnose This (August 2, 2021)

This biopsy is from a 61yo male with DM, CHF, CKD4, and an abnormal SPEP. UMOD IHC was negative. What is your diagnosis?

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This is a case of amyloid proximal tubulopathy. The tubular inclusions were Congophilic (Figure 3, Congo Red viewed under Texas Red filter) and showed apple green birefringence under polarized light (Figure 4). They were lambda restricted with no kappa (Figure 5 and Figure 6).

This patient also had PAS-pale atypical casts (Figure 7) that were lambda restricted (Figure 8 and Figure 9), but no congophilia and were consistent with lambda light chain cast nephropathy.

Amyloid proximal tubulopathy is a very rare form of paraprotein-related kidney disease, with only very few cases reported in the literature (Reference 1 and 2). It is uncertain whether it confers an increased risk of systemic amyloidosis as is the case with congophilic casts (Reference 3). In at least one autopsy case, systemic amyloid deposition was also seen in association with amyloid proximal tubulopathy (Reference 4).

References:

Larsen, Christopher P., G. Scott Borrelli, and Patrick D. Walker. “Amyloid proximal tubulopathy: a novel form of light chain proximal tubulopathy.” Clinical kidney journal 5.2 (2012): 130-132. https://academic.oup.com/ckj/article-abstract/5/2/130/342392#.YQf-cCtsibM.twitter

Amyloid Proximal Tubulopathy and Amyloid Casts: An Unusual Finding in Multiple Myeloma https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5952456/

Gibier, JB., Gnemmi, V., Glowacki, F. et al. Intratubular amyloid in light chain cast nephropathy is a risk factor for systemic light chain amyloidosis. Mod Pathol 31, 452–462 (2018). https://doi.org/10.1038/modpathol.2017.124
https://doi.org/10.1038/modpathol.2017.124 or

Ichimata S, Hata Y, Abe R, Yoshinaga T, Katoh N, Kametani F, Yazaki M, Sekijima Y, Ehara T, Nishida N. An autopsy case of amyloid tubulopathy exhibiting characteristic spheroid-type deposition. Virchows Arch. 2020 Jul;477(1):157-163. doi: 10.1007/s00428-019-02740-4. Epub 2020 Jan 13. PMID: 31932919. https://pubmed.ncbi.nlm.nih.gov/31932919/