Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Cold Spring Harb Mol Case Stud. 2021 Aug 2;7(4). doi: 10.1101/mcs.a006089. Print 2021 Aug.
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 p.V157F mutation, whereas karyotype and fluorescence in situ hybridization (FISH) identified a 17p deletion, trisomy 12, and no evidence of 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 in-frame exon 19 deletion, two mutations (p.P152Q, p.V157F), and, unexpectedly, a rearrangement. Follow-up immunohistochemistry (IHC) studies demonstrated a cyclin D1-positive lymphoid aggregate within the lung adenocarcinoma. The presence of the p.V157F mutation in the lung resection, detection of an 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 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.
全面的体细胞基因组改变特征分析使我们对肿瘤生物学的认识发生了根本性的转变。在临床实践中，这些研究可以导致诊断的改变和/或特定治疗的影响，从而实现个体化医学的承诺。在此，我们描述了一位 78 岁的女性，她因长期未治疗的慢性淋巴细胞白血病（CLL）而接受监测。外周血标本的分子研究显示 p.V157F 突变，而核型和荧光原位杂交（FISH）确定 17p 缺失、12 三体，并且没有重排的证据。正电子发射断层扫描-计算机断层扫描（PET-CT）显示多部位腹内淋巴结病和肺结节，随后的肺楔形切除术证实同时存在肺腺癌。对肺肿瘤的靶向下一代测序确定了一个 19 号外显子缺失、两个 突变（p.P152Q、p.V157F），以及意外的 重排。随后的免疫组织化学（IHC）研究显示肺腺癌内存在 cyclin D1 阳性的淋巴细胞聚集。肺切除标本中存在 p.V157F 突变、检测到 重排以及 IHC 中 cyclin D1 阳性，导致对患者血液学诊断的修正，并确认肺肿块内存在结外套细胞淋巴瘤，因此代表了“肿瘤内肿瘤”。对测序数据的人工审查表明 重排是通过插入事件发生的，其大小使得最初的 FISH 研究无法检测到。因此，对该患者已知血液恶性肿瘤的常规成像导致了意外的实体肿瘤的检测，随后对实体肿瘤进行的精准医学研究重新定义了原始的血液学诊断。
