Lymphoplasmacytic lymphoma (LPL) is a rare, indolent B-cell malignancy, with the IgG subtype being particularly uncommon. We present a case of IgG-type LPL complicated by kidney dysfunction due to lig Show more
Lymphoplasmacytic lymphoma (LPL) is a rare, indolent B-cell malignancy, with the IgG subtype being particularly uncommon. We present a case of IgG-type LPL complicated by kidney dysfunction due to light chain deposition disease (LCDD), representing the first documented instance of LCDD-related kidney impairment in this lymphoma subtype. A 65-year-old man presented with lower extremity edema and was found to have significant kidney dysfunction. Laboratory tests revealed elevated serum creatinine, heavy proteinuria, and a markedly skewed free light chain κ/λ ratio. Immunofixation electrophoresis identified an IgG-κ monoclonal protein and Bence Jones protein (κ light chain). Bone marrow biopsy confirmed LPL with a MYD88 L265P mutation, while kidney biopsy demonstrated mesangial proliferation, interstitial fibrosis, and granular κ light chain deposits consistent with LCDD. Given the rarity of IgG-type LPL with kidney involvement, this case underscores the importance of a thorough diagnostic workup in patients presenting with both hematologic malignancy and kidney dysfunction. Early recognition and appropriate management are critical for improving patient outcomes. As non-IgM LPL cases have historically been associated with poorer prognoses compared to Waldenström macroglobulinemia, the identification of underlying kidney complications such as LCDD is essential. Further accumulation of similar cases is needed to establish optimal treatment strategies. Show less
The WW domain containing E3 ubiquitin protein ligase 2 (WWP2) encodes a member of the Nedd4 family of E3 ligases, which catalyzes the final step of the ubiquitination cascade. WWP2 is involved in tumo Show more
The WW domain containing E3 ubiquitin protein ligase 2 (WWP2) encodes a member of the Nedd4 family of E3 ligases, which catalyzes the final step of the ubiquitination cascade. WWP2 is involved in tumoral growth with degradation of the tumor suppressor phosphatase and tensin homologue deleted on chromosome TEN (PTEN). However, little is known about the mechanisms and roles of WWP2 in human malignancies including oral squamous cell carcinomas (OSCCs). We found frequent WWP2 overexpression in all OSCC-derived cell lines examined that was associated with cellular growth by accelerating the cell cycle in the G1 phase via degradation of PTEN and activation of the PI3K/AKT signaling pathway. Our in vivo data of WWP2 silencing showed dramatic inhibition of tumoral growth with increased expression of PTEN. Our 104 primary OSCCs had significantly higher expression of WWP2 than their normal counterparts. Moreover, among the clinical variables analyzed, enhanced WWP2 expression was correlated with primary tumoral size and poor prognosis. These data suggested that WWP2 overexpression contributes to neoplastic promotion via the PTEN/PI3K/AKT pathway in OSCCs. WWP2 is likely to be a biomarker of tumoral progression and prognosis and a potential therapeutic target for development of anticancer drugs in OSCCs. Show less