Bhagat, Govind

Light chain deposition disease, characterized by nonamyloidogenic deposits of immunoglobulin light chains, is rare in the lung and possibly underdiagnosed due to low clinical suspicion and lack of readily accessible tests. We encountered a case of pulmonary light chain deposition disease (PLCDD) in which light chain deposits appeared crimson red with a Masson trichrome (MT) stain and salmon pink with a sulfated Alcian blue (SAB) stain. This prompted us to characterize a series of PLCDD cases and assess the utility of MT and SAB stains to distinguish them from amyloidosis. From the pathology archives of 2 institutions spanning 10 years, we identified 11 cases of PLCDD, including 7 diagnosed as such and 4 determined retrospectively. The deposits in all cases of PLCDD stained crimson red with MT and salmon pink with SAB, while the cases of pulmonary amyloid (n=10) stained blue-gray and blue-green, respectively. The immunoglobulin light chain nature of the deposits was confirmed in 10 of 11 cases by either immunofluorescence microscopy (n=5) or mass spectrometry (n=5). Transmission electron microscopy revealed osmiophilic, electron-dense deposits in all cases analyzed (n=3). An extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue type was diagnosed in 10 cases and 1 represented a plasma cell neoplasm. Our study highlights the importance of considering PLCDD in the differential diagnosis of amyloid-like deposits in the lung and the value of performing MT and SAB stains to distinguish between PLCDD and amyloidosis.

Abstract Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous entity of B-cell lymphoma. Cell-of-origin (COO) classification of DLBCL is required in routine practice by the World Health Organization classification for biological and therapeutic insights. Genetic subtypes uncovered recently are based on distinct genetic alterations in DLBCL, which are different from the COO subtypes defined by gene expression signatures of normal B cells retained in DLBCL. We hypothesize that classifiers incorporating both genome-wide gene-expression and pathogenetic variables can improve the therapeutic significance of DLBCL classification. To develop such refined classifiers, we performed targeted RNA sequencing (RNA-Seq) with a commercially available next-generation sequencing (NGS) platform in a large cohort of 418 DLBCLs. Genetic and transcriptional data obtained by RNA-Seq in a single run were explored by state-of-the-art artificial intelligence (AI) to develop a NGS-COO classifier for COO assignment and NGS survival models for clinical outcome prediction. The NGS-COO model built through applying AI in the training set was robust, showing high concordance with COO classification by either Affymetrix GeneChip microarray or the NanoString Lymph2Cx assay in 2 validation sets. Although the NGS-COO model was not trained for clinical outcome, the activated B-cell–like compared with the germinal-center B-cell–like subtype had significantly poorer survival. The NGS survival models stratified 30% high-risk patients in the validation set with poor survival as in the training set. These results demonstrate that targeted RNA-Seq coupled with AI deep learning techniques provides reproducible, efficient, and affordable assays for clinical application. The clinical grade assays and NGS models integrating both genetic and transcriptional factors developed in this study may eventually support precision medicine in DLBCL.

Breast implant-associated anaplastic large cell lymphoma (BI-ALCL) is a rare T-cell lymphoma that arises around breast implants. Most patients manifest with periprosthetic effusion, whereas a subset of patients develops a tumor mass or lymph node involvement (LNI). The aim of this study is to describe the pathologic features of lymph nodes from patients with BI-ALCL and assess the prognostic impact of LNI. Clinical findings and histopathologic features of lymph nodes were assessed in 70 patients with BI-ALCL. LNI was defined by the histologic demonstration of ALCL in lymph nodes. Fourteen (20%) patients with BI-ALCL had LNI, all lymph nodes involved were regional, the most frequent were axillary (93%). The pattern of involvement was sinusoidal in 13 (92.9%) cases, often associated with perifollicular, interfollicular, and diffuse patterns. Two cases had Hodgkin-like patterns. The 5-year overall survival was 75% for patients with LNI and 97.9% for patients without LNI at presentation (P=0.003). Six of 49 (12.2%) of patients with tumor confined by the capsule had LNI, compared with LNI in 8/21 (38%) patients with tumor beyond the capsule. Most patients with LNI achieved complete remission after various therapeutic approaches. Two of 14 (14.3%) patients with LNI died of disease compared with 0/56 (0%) patients without LNI. Twenty percent of patients with BI-ALCL had LNI by lymphoma, most often in a sinusoidal pattern. We conclude that BI-ALCL beyond capsule is associated with a higher risk of LNI. Involvement of lymph nodes was associated with decreased overall survival. Misdiagnosis as Hodgkin lymphoma is a pitfall.