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Twists and turns from “tumor in tumor” profiling: surveillance of chronic lymphocytic leukemia (CLL) leads to detection of a lung adenocarcinoma, whose genomic characterization alters the original hematologic diagnosis
Comprehensive characterization of somatic genomic alterations has led to fundamental shifts in our understanding of tumor biology. In clinical practice, these studies can lead to modifications of diagnosis and/or specific treatment implications, fulfilling the promise of personalized medicine. Herei...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8327883/ https://www.ncbi.nlm.nih.gov/pubmed/34074652 http://dx.doi.org/10.1101/mcs.a006089 |
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author | Terraf, Panieh Sholl, Lynette M. Davids, Matthew S. Awad, Mark M. Garcia, Elizabeth P. MacConaill, Laura E. Dal Cin, Paola Kim, Annette Lindeman, Neal I. Stachler, Matthew Hwang, David H. Dubuc, Adrian M. |
author_facet | Terraf, Panieh Sholl, Lynette M. Davids, Matthew S. Awad, Mark M. Garcia, Elizabeth P. MacConaill, Laura E. Dal Cin, Paola Kim, Annette Lindeman, Neal I. Stachler, Matthew Hwang, David H. Dubuc, Adrian M. |
author_sort | Terraf, Panieh |
collection | PubMed |
description | Comprehensive characterization of somatic genomic alterations has led to fundamental shifts in our understanding of tumor biology. In clinical practice, these studies can lead to modifications of diagnosis and/or specific treatment implications, fulfilling the promise of personalized medicine. Herein, we describe a 78-yr-old woman under surveillance for long-standing untreated chronic lymphocytic leukemia (CLL). Molecular studies from a peripheral blood specimen revealed a TP53 p.V157F mutation, whereas karyotype and fluorescence in situ hybridization (FISH) identified a 17p deletion, trisomy 12, and no evidence of IGH-CCND1 rearrangement. Positron emission tomography-computed tomography scan identified multistation intra-abdominal lymphadenopathy and a pulmonary nodule, and subsequent pulmonary wedge resection confirmed the presence of a concurrent lung adenocarcinoma. Targeted next-generation sequencing of the lung tumor identified an EGFR in-frame exon 19 deletion, two TP53 mutations (p.P152Q, p.V157F), and, unexpectedly, a IGH-CCND1 rearrangement. Follow-up immunohistochemistry (IHC) studies demonstrated a cyclin D1–positive lymphoid aggregate within the lung adenocarcinoma. The presence of the TP53 p.V157F mutation in the lung resection, detection of an IGH-CCND1 rearrangement, and cyclin D1 positivity by IHC led to revision of the patient's hematologic diagnosis and confirmed the extranodal presence of mantle cell lymphoma within the lung mass, thus representing a “tumor in tumor.” Manual review of the sequencing data suggested the IGH-CCND1 rearrangement occurred via an insertional event, whose size precluded detection by original FISH studies. Thus, routine imaging for this patient's known hematologic malignancy led to detection of an unexpected solid tumor, whose subsequent precision medicine studies in the solid tumor redefined the original hematological diagnosis. |
format | Online Article Text |
id | pubmed-8327883 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-83278832021-08-19 Twists and turns from “tumor in tumor” profiling: surveillance of chronic lymphocytic leukemia (CLL) leads to detection of a lung adenocarcinoma, whose genomic characterization alters the original hematologic diagnosis Terraf, Panieh Sholl, Lynette M. Davids, Matthew S. Awad, Mark M. Garcia, Elizabeth P. MacConaill, Laura E. Dal Cin, Paola Kim, Annette Lindeman, Neal I. Stachler, Matthew Hwang, David H. Dubuc, Adrian M. Cold Spring Harb Mol Case Stud Research Report Comprehensive characterization of somatic genomic alterations has led to fundamental shifts in our understanding of tumor biology. In clinical practice, these studies can lead to modifications of diagnosis and/or specific treatment implications, fulfilling the promise of personalized medicine. Herein, we describe a 78-yr-old woman under surveillance for long-standing untreated chronic lymphocytic leukemia (CLL). Molecular studies from a peripheral blood specimen revealed a TP53 p.V157F mutation, whereas karyotype and fluorescence in situ hybridization (FISH) identified a 17p deletion, trisomy 12, and no evidence of IGH-CCND1 rearrangement. Positron emission tomography-computed tomography scan identified multistation intra-abdominal lymphadenopathy and a pulmonary nodule, and subsequent pulmonary wedge resection confirmed the presence of a concurrent lung adenocarcinoma. Targeted next-generation sequencing of the lung tumor identified an EGFR in-frame exon 19 deletion, two TP53 mutations (p.P152Q, p.V157F), and, unexpectedly, a IGH-CCND1 rearrangement. Follow-up immunohistochemistry (IHC) studies demonstrated a cyclin D1–positive lymphoid aggregate within the lung adenocarcinoma. The presence of the TP53 p.V157F mutation in the lung resection, detection of an IGH-CCND1 rearrangement, and cyclin D1 positivity by IHC led to revision of the patient's hematologic diagnosis and confirmed the extranodal presence of mantle cell lymphoma within the lung mass, thus representing a “tumor in tumor.” Manual review of the sequencing data suggested the IGH-CCND1 rearrangement occurred via an insertional event, whose size precluded detection by original FISH studies. Thus, routine imaging for this patient's known hematologic malignancy led to detection of an unexpected solid tumor, whose subsequent precision medicine studies in the solid tumor redefined the original hematological diagnosis. Cold Spring Harbor Laboratory Press 2021-08 /pmc/articles/PMC8327883/ /pubmed/34074652 http://dx.doi.org/10.1101/mcs.a006089 Text en © 2021 Terraf et al.; Published by Cold Spring Harbor Laboratory Press https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/) , which permits reuse and redistribution, except for commercial purposes, provided that the original author and source are credited. |
spellingShingle | Research Report Terraf, Panieh Sholl, Lynette M. Davids, Matthew S. Awad, Mark M. Garcia, Elizabeth P. MacConaill, Laura E. Dal Cin, Paola Kim, Annette Lindeman, Neal I. Stachler, Matthew Hwang, David H. Dubuc, Adrian M. Twists and turns from “tumor in tumor” profiling: surveillance of chronic lymphocytic leukemia (CLL) leads to detection of a lung adenocarcinoma, whose genomic characterization alters the original hematologic diagnosis |
title | Twists and turns from “tumor in tumor” profiling: surveillance of chronic lymphocytic leukemia (CLL) leads to detection of a lung adenocarcinoma, whose genomic characterization alters the original hematologic diagnosis |
title_full | Twists and turns from “tumor in tumor” profiling: surveillance of chronic lymphocytic leukemia (CLL) leads to detection of a lung adenocarcinoma, whose genomic characterization alters the original hematologic diagnosis |
title_fullStr | Twists and turns from “tumor in tumor” profiling: surveillance of chronic lymphocytic leukemia (CLL) leads to detection of a lung adenocarcinoma, whose genomic characterization alters the original hematologic diagnosis |
title_full_unstemmed | Twists and turns from “tumor in tumor” profiling: surveillance of chronic lymphocytic leukemia (CLL) leads to detection of a lung adenocarcinoma, whose genomic characterization alters the original hematologic diagnosis |
title_short | Twists and turns from “tumor in tumor” profiling: surveillance of chronic lymphocytic leukemia (CLL) leads to detection of a lung adenocarcinoma, whose genomic characterization alters the original hematologic diagnosis |
title_sort | twists and turns from “tumor in tumor” profiling: surveillance of chronic lymphocytic leukemia (cll) leads to detection of a lung adenocarcinoma, whose genomic characterization alters the original hematologic diagnosis |
topic | Research Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8327883/ https://www.ncbi.nlm.nih.gov/pubmed/34074652 http://dx.doi.org/10.1101/mcs.a006089 |
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