They demonstrated LC restriction is better by immunohistochemistry on paraffin-embedded sections than by immunofluorescence of frozen sections. and unfavorable staining results for immunoglobulins, match, and both LCs on immunofluorescence (= 5). Focal interstitial selections of foamy histiocytes were noted [Physique 2d]. Thus, LCPT with CN having LC restriction was diagnosed. Open in a separate window Physique 1 Light microscopy shows vacuolations in the proximal tubular epithelial cytoplasm. (a) H and E stain, 400, which reveal fuchsinophilic droplets. (b) Masson’s trichrome stain, 1000. Direct immunofluorescence microscopic examination shows staining for light chain within the proximal tubular cytoplasm, while light chain are undetectable. (c) light chain, (d) light chain; 200 Open in a separate window Physique 2 Distal tubules showing fractured periodic acid-Schiff (PAS)-unfavorable casts (star), which on direct immunofluorescence microscopic examination demonstrated light chain restriction. (a) PAS stain, 400. (b) DIF of and light chains, 200. Podocytes exposing cytoplasmic vacuolations (arrow) and focal selections of foamy histiocytes (arrow head) can also be noted. (c and d) Masson’s trichrome stain, 1000 and 200, respectively In view of the diagnosis, patient was investigated for clonal hematopoietic disorder. MZP-54 Skeletal survey showed multiple lytic lesions in vertebrae. Serum protein electrophoresis did not show MZP-54 monoclonal proteins. Urine electrophoresis showed monoclonal protein in MZP-54 – region. Free LC assay showed serum and of 2.61 mg/dl and 2940 mg/dl, respectively (ratio of / – 0.01). Bone marrow examination revealed 43% plasma cells with expression of CD138 and thus confirming multiple myeloma. There was no glucosuria, aminoaciduria, bicarbonaturia, phosphaturia, or hyperuricosuria to suggest FS. With a diagnosis of multiple myeloma manifesting with LCPT and CN, treatment was started with combination chemotherapy of bortezomib, thalidomide and dexamethasone along with plasmapheresis. At completion of therapy at the end of 6 months, patient experienced normalization of / ratio with serum creatinine of 0.9 mg/dl and normal urine examination. Conversation First description of LCPT causing FS with paperwork of needle-shaped crystals in proximal tubular epithelial cell cytoplasm by electron microscopy was in 1957.[5] Subsequently 100 cases of LCPT have been documented in English literature.[1,2,3,4,6] The largest series of 17 cases was reported by Maldonado em et al /em . in 1975.[7] LCPT is Rabbit Polyclonal to eIF4B (phospho-Ser422) not restricted to cases with plasma cell dyscrasias and has been demonstrated in non-Hodgkin lymphomas like diffuse large B-cell lymphoma,[6] Burkitt lymphoma[8] and Waldenstrm macroglobulinemia.[9] Patients may have varied clinical presentations such as FS, kidney failure, proteinuria or osteomalacia. A vast majority of reported cases are associated with full-blown or incomplete FS. Very few cases of LCPT without FS (nine including present case) have been reported.[3,10,11] It is interesting to note that all cases of LCPT without FS show restriction. Among cases of LCPT, only 26 (including present case) with restriction have been documented.[1,2,3,8] Unlike LCPT cases with restriction, majority of which show intracytoplasmic crystals in proximal tubules, those with restriction have diverse morphology. Morphology on light microscopy varies from presence of crystals,[12] cytoplasmic vacuolations to just changes of acute tubular injury. This morphologic heterogeneity has been well-documented by Larsen em et al /em .[2] who believe that cases of -restricted LCPT are much more common than previously reported, possibly due to absence of crystals and difficulty in identifying LC restriction in tubules on immunofluorescence. They exhibited LC restriction is better by immunohistochemistry on paraffin-embedded sections than by immunofluorescence of frozen sections. They reasoned this was due to better convenience of antigens after the antigen extraction actions in immunohistochemistry. Although electron microscopy was not carried out in the index case, crystals were not noted on light microscopy, direct immunofluorescence or semi-thin sections. LCPT can occasionally be accompanied by CN[3,4] with six such cases [Table 1] being documented till date (including present case). Only three of these cases presented with FS and showed restriction. Development of proximal tubular dysfunction in cases of paraproteinemia depends on multiple factors. Normally free LCs are filtered by glomerulus and reabsorbed by proximal tubule, where they are degraded by cathepsin B and pepsin, lysosomal enzymes. Abnormal LCs secreted by neoplasms differ in V domain name, making them resistant to proteolysis MZP-54 by lysosomal enzymes.[13] LCs from patients with LCPT characteristically exhibit this property..