Cancers, Vol. 9, Pages 111: Translocation Renal Cell Carcinoma: An Update on Clinicopathological and Molecular Features

Cancers, Vol. 9, Pages 111: Translocation Renal Cell Carcinoma: An Update on Clinicopathological and Molecular Features

Cancers doi: 10.3390/cancers9090111

Authors: Kentaro Inamura

Microphthalmia-associated transcription (MiT) family translocation renal cell carcinoma (tRCC) comprises Xp11 tRCC and t(6;11) RCC. Due to the presence of fusion genes, Xp11 tRCC and t(6;11) RCC are also known as TFE3- and TFEB-rearranged RCC, respectively. TFE3 and TFEB belong to the MiT family, which regulates melanocyte and osteoclast differentiation, and TFE3- and TFEB-rearranged RCC show characteristic clinicopathological and immunohistochemical features. Recent studies identified the fusion partner-dependent clinicopathological and immunohistochemical features in TFE3-rearranged RCC. Furthermore, RCC with chromosome 6p amplification, including TFEB, was identified as a unique subtype of RCC, along with ALK-rearranged RCC. This review summarizes these recent advancements in our tRCC-related knowledge.

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Clonality and mutational profiling of a case of composite hairy cell leukemia and chronic lymphocytic leukemia

Abstract

We report a unique case of composite hairy cell leukemia (HCL) and monoclonal B-cell lymphocytosis with chronic lymphocytic leukemia (CLL) phenotype evaluated comprehensively through cell sorting and deep sequencing. The patient presented with decreased exercise tolerance and complete blood count revealed neutropenia, monocytopenia, and thrombocytopenia. The peripheral blood film was suggestive of HCL. However, a bone marrow evaluation was suspicious for composite HCL and CLL. Flow cytometry not only confirmed monoclonal kappa light chain restricted HCL and CLL populations, but also identified a kappa restricted population with co-expression of bright CD20, bright CD22, and CD11c without CD25 or CD103. Each population was isolated by cell sorting and subsequent B-cell receptor gene rearrangement analysis showed distinct rearrangements in each population. Likewise, next-generation sequencing (NGS) showed distinct mutation patterns in each of the monoclonal B-cell populations. The HCL clone harbored the signature BRAF V600E mutation, the CLL clone harbored an RB1 (L343fs*6) mutation, and the third clone was essentially negative for either mutation. In HCL, the BRAF V600E has been found in hematopoietic stem cells, raising the possibility of a common stem cell origin for composite HCL/CLL. However, our findings suggest a process of independent clonal development of multiple neoplastic B-cell populations in composite lymphoma, likely occurring somewhere after the common lymphoid progenitor stage.

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The 150 most important questions in cancer research and clinical oncology series: questions 50–56

Abstract

Since the beginning of 2017, Chinese Journal of Cancer has published a series of important questions in cancer research and clinical oncology, which sparkle diverse thoughts, interesting communications, and potential collaborations among researchers all over the world. In this article, seven more questions are presented as followed. Question 50. When tumor cells spread from primary site to distant sites, are they required to be "trained" or "armed" in the bone marrow niche prior to colonizing soft tissues? Question 51. Are there tipping points during cancer progression which can be identified for manipulation? Question 52. Can we replace molecular biomarkers by network biomarkers? Question 53. Are conventional inhibitors of key cellular processes such as cell proliferation and differentiation more effective than targeted chemotherapeutics that antagonize the downstream cell signaling network via cell-surface receptors such as epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor (VEGFR) and c-Met, or intracellular receptors such as androgen receptor (AR) and estrogen receptor (ER), by drugs like erlotinib, sunitinib and cabozantinib, or enzalutamide and tomoxifen? Question 54. How can we robustly identify the candidate causal event of somatic genome alteration (SGA) by using computational approach? Question 55. How can we systematically reveal the immune evasion mechanism exploited by each tumor and utilize such information to guide targeted therapy to restore immune sensitivity? Question 56. Can the nasopharyngeal carcinoma (NPC) patients with sarcomatoid carcinoma (SC) subtype benefit from more specific targeted therapy?

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Minimal Residual Disease Eradication in CML: Does It Really Matter?

Abstract

BCR-ABL1 tyrosine kinase inhibitors (TKIs) have improved the prognosis of chronic phase chronic myeloid leukemia (CP-CML) to an extent that survival is largely determined by non-CML mortality. Monitoring for minimal residual disease by measuring BCR-ABL1 messenger RNA is a key component of CML management. CP-CML patients who achieve a stable deep molecular response may discontinue (TKIs) with an ~ 50% chance of entering treatment-free remission (TFR). So far discontinuation of TKIs has largely been limited to clinical trials, but is on the verge of becoming a part of wider clinical practice. Careful patient selection, dense molecular monitoring, and prompt reinstitution of treatment in the event of relapse are all vital to reproduce the same level of success. Much effort has been dedicated to identifying therapeutic strategies to eliminate CML stem cells and enable to TFR in more patients. Unfortunately, despite promising preclinical data, as yet, none of the various approaches have entered clinical practice.

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Ganglioneuroblastoma in a newborn with multiple metastases: a case report

Ganglioneuroblastoma is a tumor of peripheral neuroblastic tissue which occurs predominantly in the pediatric age group; it is a rare occurrence in the newborn period with only one case reported at birth to date.

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Takayasu arteritis presenting as embolic stroke

A 52-year-old Caucasian woman presented to the emergency department with symptoms of acute ischaemic stroke (right-side weakness, confusion and aphasia) that resolved completely after administration of tissue plasminogen activator. During stroke work-up, she was found to have an enhancing infiltrate of the aorta at the level of the take-off of the great vessels, most consistent with early Takayasu arteritis. After being discharged home on steroids and dual antiplatelet therapy, she returned 2 days later with re-presentation of weakness and aphasia. Further work-up revealed two intraluminal clots in the left common carotid and left internal carotid arteries that had not been discovered during previous testing. This case illustrates the need to screen for sources of embolic stroke in patients with Takayasu arteritis, especially those with recurring symptoms.

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Oesophageal mastocytosis: eosinophilic oesophagitis without eosinophils?

A 59-year-old male with a history of lifelong asthma, allergic rhinitis and hypercholesterolaemia presented to the emergency department for management of severe substernal chest pain with radiating pain to his left arm, nausea and diaphoresis. Physical examination was unrevealing and a cardiac workup including cardiac enzymes, ECG, chest radiographs were negative for an underlying ischaemic event. A subsequent gastrointestinal workup including oesophageal manometry and oesophagogastroduodenoscopy revealed elevated lower oesophageal pressures and histopathology suggestive of mast cell proliferation, respectively. These findings were suggestive of oesophageal mastocytosis. Treatment with omeprazole-sodium bicarbonate, cetirizine, montelukast and oral budesonide promptly ameliorated his symptoms which have not recurred.

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