Genetic alterations of 9p24 in lymphomas and their impact for cancer (immuno-)therapy

Abstract

Chromosome 9 harbors several relevant oncogenes related to hematolymphoid malignancies and one specific region, 9p24, has come into the focus of attention in the last years as it contains recurrently mutant genes of therapeutic interest. The most prominent genes of this locus are programmed death ligands 1 and 2 (PDL1/PDL2), with the amplification of PDL1 being a hallmark of both classical Hodgkin and primary mediastinal B cell lymphoma, and Janus kinase 2 (JAK2), which is point-mutated in myeloproliferative neoplasms and other myeloid malignancies, and rearranged in PCM1-JAK2-positive myeloid/lymphoid neoplasms with eosinophila. Finally, this locus contains the lysine (K)-specific demethylase 4C (KDM4C/JMJD2C), which is also relevant for oncogenesis. Activation of these genes is effectuated, as exemplified, by multiple mechanisms, which is rather unique to oncogenes, since they are usually affected by just one type of mutation, and points towards the central role of these genes in tumor initiation and growth. Amplifications and, less frequently, translocations are the most common findings for PDL1/PDL2 and JAK2 in lymphomas. In this review, we describe the role of genes located on chromosome 9p24 and their derived proteins in diverse subtypes of lymphomas, with a special focus on PDL1 and PDL2, which are becoming a central target of immunotherapy, not only in classical Hodgkin lymphoma but also in various types of solid cancers. We also elucidate the role of the surgical pathologists in this setting — concerning what they can contribute — both diagnostically and predictively.

https://ift.tt/2PnMLYK

Patterns of failure in high-metastatic node number human papillomavirus-positive oropharyngeal carcinoma

Publication date: October 2018

Source: Oral Oncology, Volume 85

Author(s): Nicholas C.J. Lee, Jacqueline R. Kelly, Henry S. Park, Yi An, Benjamin L. Judson, Barbara A. Burtness, Zain A. Husain

Abstract

Background

The 8th edition American Joint Committee on Cancer staging system for resected HPV-positive oropharynx carcinoma (HPV+ OPC) highlights high node number as a critical determinant of survival. We sought to characterize outcomes and patterns of failure in patients with high pathologically involved node number oropharynx cancer.

Methods

We retrospectively identified 116 HPV+ OPC patients sequentially treated with neck dissection and either resection or intraoperative brachytherapy of the primary tumor between 2010 and 2016. External beam radiation was given based on the pathologic findings. Cox proportional hazards regression was used for multivariate analysis.

Results

With a median follow-up of 27 months, the 3-year overall survival and progression free survival (PFS) were 89% and 81%, respectively. On multivariate analysis, ≥5 involved lymph nodes was significantly associated with worse PFS (hazard ratio 4.3, 95% confidence interval (CI) 1.5–12.0, P = 0.001). Rates of 3-year locoregional recurrence (LRR) in patients with ≤4 vs ≥5 were 6% and 22% (log-rank P = 0.12). Rates of 3-year distant metastases (DM) were 12% and 53% between ≤4 and ≥5 (log-rank P < 0.001).

Conclusion

Our findings confirm that patients with 5 or more involved lymph nodes appear to have substantially worsened rates of disease recurrence. While these patients appear to be at high risk of both LRR and DM, the predominant mechanism of failure is distant, and the rate of DM in this group was over 50%. Dedicated clinical trials in this patient population are warranted with a focus on mitigating the high DM rate.

https://ift.tt/2LcAnHV

Management of otitis media with effusion in children. Société française d’ORL et de chirurgie cervico-faciale clinical practice guidelines

Publication date: August 2018

Source: European Annals of Otorhinolaryngology, Head and Neck Diseases, Volume 135, Issue 4

Author(s): F. Blanc, D. Ayache, M.N. Calmels, O. Deguine, M. François, N. Leboulanger, E. Lescanne, R. Marianowski, J. Nevoux, R. Nicollas, S. Tringali, N. Tessier, V. Franco-Vidal, P. Bordure, M. Mondain

Abstract

The Société française d'ORL et de chirurgie cervico-faciale clinical practice guidelines concern the management of otitis media with effusion (OME) in children under the age of 12 years. They are based on extensive review of MEDLINE and Cochrane Library publications in English or French from 1996 to 2016 concerning the methods of diagnosis and assessment of otitis media with effusion, as well as the efficacy of tympanostomy tubes and medical and surgical treatments of OME.

https://ift.tt/2nS40Fb

Editorial Board

Publication date: August 2018

Source: European Annals of Otorhinolaryngology, Head and Neck Diseases, Volume 135, Issue 4

Author(s):

https://ift.tt/2LdIofw

Contents

Publication date: August 2018

Source: European Annals of Otorhinolaryngology, Head and Neck Diseases, Volume 135, Issue 4

Author(s):

https://ift.tt/2nThxMI

Hypermucoviscous Klebsiella pneumoniae liver abscess requiring liver resection

Description 

A 41-year-old healthy woman from China presented to her local hospital with a 4-day history of fevers, malaise and epigastric pain. On examination, she had localised right upper quadrant abdominal pain on palpation. Laboratory investigations showed leukocytosis (13.8x10⁹/L), thrombocytopaenia (82x10⁹/L) and elevated alanine transaminase (184 U/L). An abdominal CT scan revealed a 10x8x9 cm multiloculated collection within the right liver lobe, with a second nodular septated collection under the left subcapsular region (figure 1). Her blood cultures returned positive for Klebsiella pneumoniae, resistant to ampicillin and susceptible to cefazolin, ciprofloxacin and meropenem. She was admitted to hospital and started on ceftriaxone.

Figure 1

Abdominal CT showing large multiloculated liver abscesses in segments 2/3 of the left liver lobe (white arrow) and segments 6/7 of the right liver lobe (black arrow).

Diagnostic and therapeutic ultrasound-guided 10F drains were inserted into both abscesses...

https://ift.tt/2LcHnnZ

Paediatric parapharyngeal ganglioneuroma

A 17-year-old man initially presented to his primary care physician with throat pain for 1 week and was started on amoxicillin. After four additional days of ongoing pain and difficulty swallowing with decreased oral intake, he presented to the emergency department. Exam showed fullness to the right posterior oropharynx and palpable mass in the right neck without stridor. Initial imaging was soft tissue neck CT with contrast, which showed cystic 8 cm mass in the parapharyngeal space. Patient additionally underwent MRI, which showed an 8.6 cm mass in the right posterior oropharynx with obliteration of the vallecula. Differential diagnosis included abscess; therefore, ear, nose, and throat (ENT) specialist was consulted for possible drainage. Intraoperatively, there was no abscess; alternatively a biopsy was obtained, which was identified by pathology as a ganglioneuroma. Patient was referred to paediatric ENT specialist, underwent extensive resection confirming diagnosis of ganglioneuroma and did well postoperatively.

https://ift.tt/2Plm0Em