PMID- 34074652
OWN - NLM
STAT- MEDLINE
DCOM- 20220104
LR  - 20220301
IS  - 2373-2873 (Electronic)
IS  - 2373-2873 (Linking)
VI  - 7
IP  - 4
DP  - 2021 Aug
TI  - 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.
LID - 10.1101/mcs.a006089 [doi]
LID - a006089
AB  - 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.
CI  - (c) 2021 Terraf et al.; Published by Cold Spring Harbor Laboratory Press.
FAU - Terraf, Panieh
AU  - Terraf P
AD  - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New 
      York 10065, USA.
FAU - Sholl, Lynette M
AU  - Sholl LM
AD  - Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 
      Boston, Massachusetts 02115, USA.
FAU - Davids, Matthew S
AU  - Davids MS
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, 
      Massachusetts 02215, USA.
FAU - Awad, Mark M
AU  - Awad MM
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, 
      Massachusetts 02215, USA.
FAU - Garcia, Elizabeth P
AU  - Garcia EP
AD  - Center for Advanced Molecular Diagnostics, Brigham and Women's Hospital, Harvard 
      Medical School, Boston, Massachusetts 02115, USA.
FAU - MacConaill, Laura E
AU  - MacConaill LE
AD  - Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 
      Boston, Massachusetts 02115, USA.
FAU - Dal Cin, Paola
AU  - Dal Cin P
AD  - Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 
      Boston, Massachusetts 02115, USA.
FAU - Kim, Annette
AU  - Kim A
AD  - Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 
      Boston, Massachusetts 02115, USA.
FAU - Lindeman, Neal I
AU  - Lindeman NI
AD  - Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 
      Boston, Massachusetts 02115, USA.
FAU - Stachler, Matthew
AU  - Stachler M
AD  - Department of Pathology, University of California San Francisco, San Francisco, 
      California 94143, USA.
FAU - Hwang, David H
AU  - Hwang DH
AD  - Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 
      Boston, Massachusetts 02115, USA.
FAU - Dubuc, Adrian M
AU  - Dubuc AM
AD  - Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 
      Boston, Massachusetts 02115, USA.
LA  - eng
GR  - P30 CA008748/CA/NCI NIH HHS/United States
PT  - Case Reports
PT  - Journal Article
DEP - 20210802
PL  - United States
TA  - Cold Spring Harb Mol Case Stud
JT  - Cold Spring Harbor molecular case studies
JID - 101660017
RN  - 0 (Biomarkers, Tumor)
SB  - IM
MH  - Adenocarcinoma of Lung/*diagnosis/genetics
MH  - Aged
MH  - Biomarkers, Tumor/genetics
MH  - Diagnostic Errors
MH  - Female
MH  - Gene Expression Profiling
MH  - Gene Rearrangement
MH  - High-Throughput Nucleotide Sequencing
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/*diagnosis/genetics
MH  - Lung Neoplasms/*diagnosis/genetics
MH  - Lymphoma, Mantle-Cell/*diagnosis/genetics
MH  - Neoplasms, Multiple Primary/*diagnosis/genetics
MH  - Positron Emission Tomography Computed Tomography
PMC - PMC8327883
OTO - NOTNLM
OT  - chronic lymphatic leukemia
OT  - hematological neoplasm
OT  - lung adenocarcinoma
EDAT- 2021/06/03 06:00
MHDA- 2022/01/05 06:00
PMCR- 2021/08/01
CRDT- 2021/06/02 05:56
PHST- 2021/02/22 00:00 [received]
PHST- 2021/05/03 00:00 [accepted]
PHST- 2021/06/03 06:00 [pubmed]
PHST- 2022/01/05 06:00 [medline]
PHST- 2021/06/02 05:56 [entrez]
PHST- 2021/08/01 00:00 [pmc-release]
AID - mcs.a006089 [pii]
AID - 10.1101/mcs.a006089 [doi]
PST - epublish
SO  - Cold Spring Harb Mol Case Stud. 2021 Aug 2;7(4):a006089. doi: 
      10.1101/mcs.a006089. Print 2021 Aug.