Nischala Ammannagari

Anaplastic Multiple Myeloma: An Aggressive Variant With a Poor Response to Novel Therapies

Introduction Anaplastic multiple myeloma (AMM) is a very rare and aggressive morphologic variant of multiple myeloma with a historically poor prognosis. The term “anaplastic myeloma” is used to describe a plasma cell malignancy involving immature plasma cells of pleomorphic morphology with high-grade transformation and extramedullary involvement with large, poorly differentiated cells. Anaplastic morphology can be present at the initial diagnosis or can appear later in the disease course. Historically, this disease has been very resistant to chemotherapy. We have described 2 cases of anaplastic myeloma and the poor response to novel myeloma therapies.

Clinicopathological characteristics and outcomes of rare histologic subtypes of gallbladder cancer over two decades: A population-based study

Background There is limited literature about the clinicopathological characteristics and outcomes of rare histologic variants of gallbladder cancer (GBC). Methods Using SEER database, surgically managed GBC patients with microscopically confirmed adenocarcinoma, adenosquamous/squamous cell carcinoma and papillary carcinoma were identified from 1988 to 2009. Patients with second primary cancer and distant metastasis at presentation were excluded. The effect of clinicopathological variables on overall survival (OS) and disease specific survival (DSS) were analyzed using univariate and multivariate proportional hazards modeling. All associations were considered statistically significant at an alpha error of 0.01. Results Out of 4738 cases, 217 adenosquamous/squamous (4.6%), 367 papillary (7.7%), and 4154 adenocarcinomas (87.7%) were identified. Median age was 72 years. Higher tumor grade (grade 2, 3, 4 versus grade 1), higher T stage (T2, T3, T4 versus T1), lymph node positivity (N1 versus N0) and adenosquamous/squamous histology (versus adenocarcinoma) had worse OS and DSS (p < .001). Papillary GBC had better OS and DSS than adenocarcinoma (HR = 0.7; p < .001). Radical surgery (versus simple cholecystectomy) had better OS (HR = 0.83, p = 0.002) in multivariate analysis. OS rates at 3 and 5 years were 0.56 and 0.44 for papillary, 0.3 and 0.22 for adenocarcinoma, and 0.14 and 0.12 for adenosquamous/squamous histology, while DSS rates at 3 and 5 years were 0.67 and 0.61 for papillary, 0.38 and 0.31 for adenocarcinoma, and 0.17 and 0.16 for adenosquamous/squamous subtypes respectively. Conclusion Papillary GBC had better survival outcomes while adenosquamous/squamous GBC had worse survival outcomes compared to gallbladder adenocarcinoma.

Abstract 620: Tumor microenvironment heterogeneity is not identified across multiple histologically similar tumors from the same patient

Introduction: Tumor heterogeneity has been well documented for mutational analysis in virtually all types of tumors and is accepted as a true finding. Heterogeneity of the tumor microenvironment (TME) in the context of response to checkpoint inhibitors has not been well studied; the belief is that variation will be identified across multiple tumors from the same patient. The expectation is that multiple tumors from a single patient would demonstrate extensive TME heterogeneity driven by the neoplasm. Methods: We validated and utilized a targeted RNA-seq immune panel of >350 genes to interrogate the TME of 49 different tumors from 17 unique patients. These samples for one patient represented primary and metastatic tumors that were separated by multiple years. Prior to this study we built a reference database of RNA-seq immune results for this panel of 167 samples. An in-depth analysis of genes associated with checkpoint inhibition (CPI) and tumor infiltrating lymphocytes (TILs) were the focus of the comparative analysis. Unsupervised analysis and gene rank by RNA-seq were the primary modes of comparison. Results: For more than one-half of these patients the different tumors for a single patient separated by multiple years more closely resembled the other tumors from that patient than the reference population by unsupervised clustering. When ranked by LOW, MODERATE, or HIGH expression of genes associated with TILs or CPI the results for the majority of patients were highly concordant: LOW TILs / LOW CPI associated gene expression. Conclusion: Our results support a paradigm shift in the influence of the host on TME heterogeneity with evidence that the host and not the neoplastic cells are the primary determining factor. TME heterogeneity is not identified across multiple tumors of the same histology collected from different sites across time points from the same patient. This study does not evaluate multiple primary tumors from the same patient, but is an additional study we have planned. Citation Format: Carl D. Morrison, Jeffrey Conroy, Sean Glenn, Blake Burgher, Sarabjot Pabla, Maochun Qin, Antonios Papanicolau-Sengos, Jon Andreas, Vincent Giamo, Mary Nesline, Shipra Gandhi, Manu Pandey, Nischala Ammannagari, Kunle Odunsi, Marc Ernstoff, Mark Gardner. Tumor microenvironment heterogeneity is not identified across multiple histologically similar tumors from the same patient [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 620. doi:10.1158/1538-7445.AM2017-620