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Hu X, Wang W, Zhong YW, An PG, Zhang J, Wu WJ. Magnetic resonance neurography: Preoperative assessment of facial nerve invasion in malignant parotid gland tumors. JOURNAL OF STOMATOLOGY, ORAL AND MAXILLOFACIAL SURGERY 2025:102329. [PMID: 40220868 DOI: 10.1016/j.jormas.2025.102329] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/04/2025] [Revised: 03/31/2025] [Accepted: 04/09/2025] [Indexed: 04/14/2025]
Abstract
BACKGROUNDS Facial nerve invasion (FNI) in parotid gland malignancies significantly impacts treatment outcomes and prognosis. Accurate preoperative assessment of FNI is crucial for surgical planning and tumor staging. Conventional imaging modalities often fail to visualize the facial nerve and assess FNI. OBJECTS This study aims to evaluate the predictive efficacy of magnetic resonance neurography (MRN) in detecting FNI in parotid gland malignancies, with the goal of aiding tumor staging and treatment decision-making. METHODS 28 patients with parotid gland malignancies were included. MRN was utilized to visualize the intraparotid facial nerve and determine its relationship with the tumor. MRN results were then used to predict FNI and re-evaluate the clinical T stage. Surgical records were used for validation. Statistical analysis was performed using chi-square tests and net reclassification improvement (NRI). RESULTS The display rates of the main trunk and other divisions (temporofacial and cervicofacial) of the intraparotid facial nerve were 100 %, 96.4 %, and 96.4 %, respectively. Twenty-three patients (82.1 %) matched the surgical findings (P < 0.01). MRN-indicated infiltration performed better than facial paralysis in predicting FNI. Tumors of stage T4a were underestimated in 22.7 % of cases (n = 5), and evaluation of clinical T stage with MRN was superior to that without MRN (NRI > 0, Z = 2.17, P = 0.03). CONCLUSIONS MRN can provide valuable information for predicting FNI in parotid gland malignancies, thereby improving tumor staging and aiding treatment decision-making.
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Affiliation(s)
- Xiao Hu
- Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, PR China; National Center for Stomatology & National Clinical Research Center for Oral Diseases, Beijing, PR China; Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, PR China
| | - Wei Wang
- Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, PR China; National Center for Stomatology & National Clinical Research Center for Oral Diseases, Beijing, PR China; Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, PR China
| | - Yi-Wei Zhong
- Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, PR China; National Center for Stomatology & National Clinical Research Center for Oral Diseases, Beijing, PR China; Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, PR China
| | - Pu-Gen An
- Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, PR China; National Center for Stomatology & National Clinical Research Center for Oral Diseases, Beijing, PR China; Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, PR China
| | - Jie Zhang
- Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, PR China; National Center for Stomatology & National Clinical Research Center for Oral Diseases, Beijing, PR China; Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, PR China
| | - Wen-Jie Wu
- Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, PR China; National Center for Stomatology & National Clinical Research Center for Oral Diseases, Beijing, PR China; Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, PR China.
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Li KY, Kwok HM, Pan NY, Cheng LF, Ma KFJ. Pre-treatment and post-treatment nasopharyngeal carcinoma imaging: imaging updates, pearls and pitfalls. Neuroradiology 2025; 67:1023-1047. [PMID: 40214770 PMCID: PMC12041163 DOI: 10.1007/s00234-025-03596-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2024] [Accepted: 03/18/2025] [Indexed: 04/30/2025]
Abstract
PURPOSE Nasopharyngeal carcinoma (NPC) is endemic in Southeast Asia, requiring precise imaging for personalized treatment. This review highlights key imaging challenges and updates from recent literature, emphasizing findings that impact oncological management. METHODS We discuss common and uncommon clinical entities, detailing salient imaging features and diagnostic distinctions to aid accurate interpretation. RESULTS In the pre-treatment setting, leveraging the characteristic MR signals and spread patterns of NPC aids in defining the tumor volume for accurate staging and radiotherapy contouring. Key diagnostic challenges include differentiating tumor from benign hyperplasia, skull base osteomyelitis, and other skull base tumors. Perineural tumor spread, radiological extranodal extension and nodal necrosis further refine primary tumor and nodal assessment. In the post-treatment setting, the key question is whether tumor recurrence exists. Diagnostic challenges involve distinguishing tumor recurrence from scar tissue, post-radiation nasopharyngeal necrosis, or hypertrophied cervical ganglia. For recurrences, endoscopic nasopharyngectomy has emerged as the preferred approach over open surgery or re-irradiation. The text highlights characteristic post-treatment appearances and emphasizes recognizing these patterns to avoid misinterpretation and guide appropriate management. CONCLUSION Imaging plays a pivotal role in NPC precision oncology. Mastering imaging pearls and pitfalls empowers radiologists to provide clinicians with reliable, actionable guidance.
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Affiliation(s)
- Kwok Yan Li
- Department of Diagnostic and Interventional Radiology, Princess Margaret Hospital, Hong Kong SAR, China
| | - Hoi Ming Kwok
- Department of Diagnostic and Interventional Radiology, Princess Margaret Hospital, Hong Kong SAR, China.
- Department of Imaging and Interventional Radiology, Chinese University of Hong Kong, Hong Kong SAR, China.
| | - Nin Yuan Pan
- Department of Diagnostic and Interventional Radiology, Princess Margaret Hospital, Hong Kong SAR, China
| | - Lik Fai Cheng
- Department of Diagnostic and Interventional Radiology, Princess Margaret Hospital, Hong Kong SAR, China
| | - Ka Fai Johnny Ma
- Department of Diagnostic and Interventional Radiology, Princess Margaret Hospital, Hong Kong SAR, China
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Rutkowski K, Gola M, Godlewski J, Starzyńska A, Marvaso G, Mastroleo F, Giulia Vincini M, Porazzi A, Zaffaroni M, Jereczek-Fossa BA. Understanding the role of nerves in head and neck cancers - a review. Oncol Rev 2025; 18:1514004. [PMID: 39906323 PMCID: PMC11791411 DOI: 10.3389/or.2024.1514004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2024] [Accepted: 12/03/2024] [Indexed: 02/06/2025] Open
Abstract
Worldwide, head and neck cancers (HNCs) account for approximately 900,000 cases and 500,000 deaths annually, with their incidence continuing to rise. Carcinogenesis is a complex, multidimensional molecular process leading to cancer development, and in recent years, the role of nerves in the pathogenesis of various malignancies has been increasingly recognized. Thanks to the abundant innervation of the head and neck region, peripheral nervous system has gained considerable interest for its possible role in the development and progression of HNCs. Intratumoral parasympathetic, sympathetic, and sensory nerve fibers are emerging as key players and potential targets for novel anti-cancer and pain-relieving medications in different tumors, including HNCs. This review explores nerve-cancer interactions, including perineural invasion (PNI), cancer-related axonogenesis, neurogenesis, and nerve reprogramming, with an emphasis on their molecular mechanisms, mediators and clinical implications. PNI, an adverse histopathologic feature, has been widely investigated in HNCs. However, its prognostic value remains debated due to inconsistent results when classified dichotomously (present/absent). Emerging evidence suggests that quantitative and qualitative descriptions of PNI may better reflect its clinical usefulness. The review also examines therapies targeting nerve-cancer crosstalk and highlights the influence of HPV status on tumor innervation. By synthesizing current knowledge, challenges, and future perspectives, this review offers insights into the molecular basis of nerve involvement in HNCs and the potential for novel therapeutic approaches.
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Affiliation(s)
- Krzysztof Rutkowski
- Department of Hematology, Transplantology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland
| | - Michał Gola
- Department of Human Histology and Embryology, Collegium Medicum, School of Medicine, University of Warmia and Mazury, Olsztyn, Poland
- Department of Oncology and Immuno-Oncology, Clinical Hospital of the Ministry of Internal Affairs and Administration with the Warmia-Mazury Oncology Centre, Olsztyn, Poland
| | - Janusz Godlewski
- Department of Human Histology and Embryology, Collegium Medicum, School of Medicine, University of Warmia and Mazury, Olsztyn, Poland
- Department of Surgical Oncology, Clinical Hospital of the Ministry of Internal Affairs and Administration with the Warmia-Mazury Oncology Centre, Olsztyn, Poland
| | - Anna Starzyńska
- Department of Oral Surgery, Medical University of Gdańsk, Gdańsk, Poland
- Department of Otolaryngology, Phoniatrics and Audiology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland
| | - Giulia Marvaso
- Division of Radiation Oncology, European Institute of Oncology (IEO), Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
| | - Federico Mastroleo
- Division of Radiation Oncology, European Institute of Oncology (IEO), Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
| | - Maria Giulia Vincini
- Division of Radiation Oncology, European Institute of Oncology (IEO), Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
| | - Alice Porazzi
- Division of Radiation Oncology, European Institute of Oncology (IEO), Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, Italy
| | - Mattia Zaffaroni
- Division of Radiation Oncology, European Institute of Oncology (IEO), Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, Italy
| | - Barbara Alicja Jereczek-Fossa
- Division of Radiation Oncology, European Institute of Oncology (IEO), Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
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Warner KA, Herzog AE, Sahara S, Nör F, Castilho RM, Demirci H, Chepeha DB, Polverini PJ, Nör JE. Establishment and characterization of cMYB-expressing human salivary adenoid cystic carcinoma cell lines (UM-HACC-14, UM-HACC-6) and matching patient-derived xenograft model (UM-PDX-HACC-14). Oral Surg Oral Med Oral Pathol Oral Radiol 2024; 138:516-531. [PMID: 38971694 PMCID: PMC11827064 DOI: 10.1016/j.oooo.2024.06.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Revised: 05/31/2024] [Accepted: 06/06/2024] [Indexed: 07/08/2024]
Abstract
OBJECTIVE Limited availability of authentic human adenoid cystic carcinoma (ACC) cell lines has hindered progress in understanding mechanisms underpinning the biology of this disease and the development of safe and effective therapies. STUDY DESIGN Surgical human ACC specimens (UM-HACC-6, UM-HACC-14) were dissociated into single cell suspensions and cultured in fibronectin-coated flasks. Alternatively, tumor fragments were transplanted subcutaneously into female immunodeficient (SCID) mice to establish patient-derived xenograft tumors (PDX; UM-PDX-HACC-14). RESULTS Both ACC cell lines showed continuous growth in monolayers for over 100 passages. Total RNA-Seq, RT-PCR, and FISH analysis revealed that both are MYB-NFIB fusion negative. Western blots revealed passage-dependent expression of E-Cadherin, PCNA, p63, phospho-c-MYB, and NFIB. Both, UM-HACC-14 and UM-HACC-6 cells exhibited tumorigenic potential when injected orthotopically into mouse submandibular glands. CONCLUSION UM-HACC-14, patient-matching UM-PDX-HACC-14, and the UM-HACC-6 cell line are new, authenticated preclinical models of ACC that are well suited for mechanistic and developmental therapeutics studies.
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Affiliation(s)
- Kristy A Warner
- Department of Cariology, Restorative Sciences, Endodontics, University of Michigan School of Dentistry, Ann Arbor, MI, USA
| | - Alexandra E Herzog
- Department of Cariology, Restorative Sciences, Endodontics, University of Michigan School of Dentistry, Ann Arbor, MI, USA
| | - Sosuke Sahara
- Department of Cariology, Restorative Sciences, Endodontics, University of Michigan School of Dentistry, Ann Arbor, MI, USA
| | - Felipe Nör
- Department of Periodontics and Oral Medicine, School of Dentistry, Ann Arbor, MI, USA
| | - Rogerio M Castilho
- Department of Periodontics and Oral Medicine, School of Dentistry, Ann Arbor, MI, USA
| | - Hakan Demirci
- Department of Opthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan, Ann Arbor, MI, USA
| | - Douglas B Chepeha
- Department of Otolaryngology, University of Toronto, Toronto, ON, Canada
| | - Peter J Polverini
- Department of Otolaryngology, University of Michigan School of Medicine, Ann Arbor, MI, USA; Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA; Department of Periodontics and Oral Medicine, School of Dentistry, Ann Arbor, MI, USA; Department of Pathology, University of Michigan, Ann Arbor, MI, USA
| | - Jacques E Nör
- Department of Cariology, Restorative Sciences, Endodontics, University of Michigan School of Dentistry, Ann Arbor, MI, USA; Department of Biomedical Engineering, University of Michigan College of Engineering, Ann Arbor, MI, USA; Department of Otolaryngology, University of Michigan School of Medicine, Ann Arbor, MI, USA; Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA.
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Hsieh KCJ, Addae-Mensah K, Alrohaibani Y, Goad A, Learned K. Perineural Spread of Tumor in the Skull Base and Head and Neck. Oral Maxillofac Surg Clin North Am 2023:S1042-3699(23)00006-7. [PMID: 37005170 DOI: 10.1016/j.coms.2023.02.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/03/2023]
Abstract
Perineural tumor spread (PNS) is a well-recognized entity in head and neck cancers and represents a mode of metastasis along nerves. The trigeminal and facial nerves are most affected by PNS, and their connections are reviewed. MRI is the most sensitive modality for detecting PNS, and their anatomy and interconnections are reviewed. MRI is the most sensitive modality for detecting PNS, and imaging features of PNS and important imaging checkpoints are reviewed. Optimal imaging protocol and techniques are summarized as well as other entities that can mimic PNS.
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Wang J, Yang Z, Liu Y, Li H, Yang X, Gao W, Zhao Q, Yang X, Wei J. The GAL/GALR2 axis promotes the perineural invasion of salivary adenoid cystic carcinoma via epithelial-to-mesenchymal transition. Cancer Med 2023; 12:4496-4509. [PMID: 36039037 PMCID: PMC9972115 DOI: 10.1002/cam4.5181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Revised: 08/11/2022] [Accepted: 08/12/2022] [Indexed: 11/05/2022] Open
Abstract
BACKGROUND Perineural invasion (PNI) is a typical pathological characteristic of salivary adenoid cystic carcinoma (SACC) and other neurotrophic cancers. The mechanism of the neural microenvironment controlling tumor progression during the PNI process is unclear. In the present study, we investigated the role and molecular mechanisms of nerve-derived neuropeptide galanin (GAL) and its receptor (GALR2) in the regulation of PNI in SACC. METHODS Immunohistochemistry staining and clinical association studies were performed to analyze the expression of GAL and GALR2 in SACC tissues and their clinical value. Dorsal root ganglion or SH-SY5Y cells were co-cultured with SACC cells in vitro to simulate the interactions between the neural microenvironment and tumor cells, and a series of assays including transcriptome sequencing, Western blot, and Transwell were performed to investigate the role and molecular mechanism of GAL and GALR2 in the regulation of SACC cells. Moreover, both the in vitro and in vivo PNI models were established to assess the potential PNI-specific therapeutic effects by blocking the GAL/GALR2 axis. RESULTS GAL and GALR2 were highly expressed in SACC tissues, and were associated with PNI and poor prognosis in SACC patients (p < 0.05). Nerve-derived GAL activated GALR2 expression in SACC cells and induced epithelial-to-mesenchymal transition (EMT) in SACC cells. Adding human recombinant GAL to the co-culture system promoted the proliferation, migration, and invasion of SACC cells significantly, but inhibited the apoptosis of SACC cells. Adding M871, a specific antagonist of GALR2, significantly blocked the above effects (p < 0.05) and inhibited the PNI of SACC cells in vitro and in vivo (p < 0.05). CONCLUSIONS This study demonstrated that nerve-derived GAL activated GALR2 expression, and promoted EMT in SACC cells, thereby enhancing the PNI process. Interruption of the GAL/GALR2 axis might be a novel strategy for anti-PNI therapy for SACC.
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Affiliation(s)
- Jun Wang
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases, and Shaanxi Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Zihui Yang
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases, and Shaanxi Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Yuanyang Liu
- Senior Department of Neurosurgery, First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Huan Li
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases, and Shaanxi Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Xiangming Yang
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases, and Shaanxi Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Wanpeng Gao
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases, and Shaanxi Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Qi Zhao
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases, and Shaanxi Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Xinjie Yang
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases, and Shaanxi Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Jianhua Wei
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases, and Shaanxi Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi'an, China
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Riju J, Tirkey AJ, Babu M, Anto R, Baitule AM, Vidya K, Agarwal M. Difference in clinical presentation and their significance in oral squamous cell carcinoma: A retrospective analysis. J Cancer Res Ther 2023; 19:S685-S690. [PMID: 38384040 DOI: 10.4103/jcrt.jcrt_767_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 07/31/2022] [Indexed: 02/23/2024]
Abstract
BACKGROUND Oral squamous cell carcinoma (OSCC) remains the most common cancer among Indian men. OSCC involving the tongue and bucco alveolar complex (BAC) behaves differently. Nevertheless, the differences in clinical features and symptoms between the two subsites and their relation to pathology remain largely unexplored. STUDY DESIGN The study compared various clinical parameters and pathological factors between tongue cancer patients and patients with BAC cancer. RESULTS Among 474 patients, 232 had tongue cancer and 242 had BAC cancer. Except for the ulcer, 30% of patients with OSCC were asymptomatic at presentation. Compared to tongue cancers, lesions confined to BAC present at an advanced stage (P = 0.006). Multivariate analysis showed that dysphagia in tongue cancer (P = 0.020) and external swelling or lesion in BAC cancers (P = 0.002) were significant predictors of an advanced stage of the disease. On histopathology, perineural invasion (PNI) was significantly associated with tongue (P = 0.008) compared to BAC cancers (P = 0.015). Cancers of the tongue with pain and referred otalgia had a significantly higher depth of invasion (DOI), compared to those without pain (DOI - no pain 6.9 mm, pain 9.9 mm, and referred otalgia 11.4 mm). CONCLUSIONS Patients with OSCC present late and in an advanced stage of the disease. Among tongue cancers, clinical history of pain was significantly associated with DOI and PNI, the significance of which needs to be prospectively analyzed. Clinical history in OSCC can be used as predicting factor for an advanced pathological stage of the disease. It also had an influence on various pathological characters, which is subsite specific.
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Affiliation(s)
- Jeyashanth Riju
- Department of Head and Neck Surgery, Christian Medical College, Vellore, Tamil Nadu, India
| | - Amit Jiwan Tirkey
- Department of Head and Neck Surgery, Christian Medical College, Vellore, Tamil Nadu, India
| | - Malavika Babu
- Department of Biostatistics, Christian Medical College, Vellore, Tamil Nadu, India
| | - Ronald Anto
- Department of Head and Neck Surgery, Christian Medical College, Vellore, Tamil Nadu, India
| | - Amey Madhav Baitule
- Department of Pathology, Christian Medical College, Vellore, Tamil Nadu, India
| | - Konduru Vidya
- Department of Head and Neck Surgery, Christian Medical College, Vellore, Tamil Nadu, India
| | - Mansi Agarwal
- Department of Head and Neck Surgery, Christian Medical College, Vellore, Tamil Nadu, India
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Fang C, Zhong Y, Chen T, Li D, Li C, Qi X, Zhu J, Wang R, Zhu J, Wang S, Ruan Y, Zhou M. Impairment mechanism of nasal mucosa after radiotherapy for nasopharyngeal carcinoma. Front Oncol 2022; 12:1010131. [PMID: 36591522 PMCID: PMC9797686 DOI: 10.3389/fonc.2022.1010131] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Accepted: 11/28/2022] [Indexed: 12/23/2022] Open
Abstract
The nasal mucosa, which performs the crucial functions of filtering, humidifying and temperature regulation, is one of the most vulnerable areas of nasopharyngeal carcinoma (NPC) patients after radiotherapy (RT). Following RT, NPC patients experience a series of pathological changes in the nasal mucosa, ultimately leading to physiological dysfunction of the nasal epithelium. This article systematically reviews the clinical and pathological manifestations of RT-related nasal damage in NPC patients and summarizes the potential mechanism of damage to the human nasal epithelium by RT. Finally, we outline the current mechanistic models of nasal epithelial alterations after RT in NPC patients and provide additional information to extend the in-depth study on the impairment mechanisms of the nasal mucosa resulting from RT. We also describe the relationship between structural and functional alterations in the nasal mucosa after RT to help mitigate and treat this damage and provide insights informing future clinical and fundamental investigations.
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Affiliation(s)
- Caishan Fang
- The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yu Zhong
- Department of Radiotherapy, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Tengyu Chen
- Department of Otolaryngology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
| | - Dan Li
- The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Chunqiao Li
- Department of Otolaryngology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Xiangjun Qi
- The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Junxia Zhu
- The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Ruizhi Wang
- The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Jinxiang Zhu
- The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Shunlan Wang
- Department of Otolaryngology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yan Ruan
- Department of Otolaryngology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China,*Correspondence: Min Zhou, ; Yan Ruan,
| | - Min Zhou
- Department of Otolaryngology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China,*Correspondence: Min Zhou, ; Yan Ruan,
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Dhillon M, Mackie G, Singh D. 18F-FDG PET, contrast CT and MRI to comprehensively diagnose and assess rare perineural spread of squamous cell carcinoma to the greater auricular nerve. Radiol Case Rep 2022; 17:2106-2110. [PMID: 35464802 PMCID: PMC9024344 DOI: 10.1016/j.radcr.2022.03.080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Revised: 03/14/2022] [Accepted: 03/20/2022] [Indexed: 12/04/2022] Open
Abstract
We present a case of a 78-year-old male with a primary parotid squamous cell carcinoma which spread via the left facial, trigeminal and greater auricular nerves. The patient presented with left facial droop and paraesthesia. Initial MRI scans demonstrated involvement of the trigeminal and facial nerves with no sign of a primary lesion. Abnormal enhancement within the left parotid substance on FDG PET-CT demonstrated the primary malignancy which was confirmed on histology by core biopsy. There was also focal avidity along the course of the left greater auricular nerve consistent with perineural infiltration, extending from the posterior aspect of the parotid to the left cervical plexus at C2/C3. To our knowledge, this is the second case of squamous cell carcinoma perineural spread to the greater auricular nerve imaged on FDG PET-CT scanning. This case highlights the importance of multimodality imaging correlation in the workup of primary head and neck malignancies and associated perineural spread, which is essential in adjuvant radiation therapy planning to reduce local recurrence, improve prognosis and overall survival.
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Abdelaziz TT, Abdel Razek AAK. Magnetic Resonance Imaging of Perineural Spread of Head and Neck Cancer. Magn Reson Imaging Clin N Am 2021; 30:95-108. [PMID: 34802584 DOI: 10.1016/j.mric.2021.06.017] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Perineural tumor spread (PNTS) is one of the important methods of tumoral spread in head and neck cancers. It consists of a complex process that entails the production of certain chemicals or the production of certain cell receptors. Histologic type and primary tumor site play an important role in PNTS. Any nerve could be affected; however, the trigeminal and facial nerves are the most involved nerves. Magnetic resonance imaging and computed tomography detect the primary and secondary signs of PNTS. Functional imaging such as diffusion-weighted imaging and hybrid imaging act as problem-solving techniques.
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Affiliation(s)
- Tougan Taha Abdelaziz
- Department of Diagnostic Radiology, Ain Shams Faculty of Medicine, 56 Ramses St, Abbasia, Cairo 1158, Egypt.
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Peripheral nerve injury and sensitization underlie pain associated with oral cancer perineural invasion. Pain 2021; 161:2592-2602. [PMID: 32658150 DOI: 10.1097/j.pain.0000000000001986] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Cancer invading into nerves, termed perineural invasion (PNI), is associated with pain. Here, we show that oral cancer patients with PNI report greater spontaneous pain and mechanical allodynia compared with patients without PNI, suggesting that unique mechanisms drive PNI-induced pain. We studied the impact of PNI on peripheral nerve physiology and anatomy using a murine sciatic nerve PNI model. Mice with PNI exhibited spontaneous nociception and mechanical allodynia. Perineural invasion induced afterdischarge in A high-threshold mechanoreceptors (HTMRs), mechanical sensitization (ie, decreased mechanical thresholds) in both A and C HTMRs, and mechanical desensitization in low-threshold mechanoreceptors. Perineural invasion resulted in nerve damage, including axon loss, myelin damage, and axon degeneration. Electrophysiological evidence of nerve injury included decreased conduction velocity, and increased percentage of both mechanically insensitive and electrically unexcitable neurons. We conclude that PNI-induced pain is driven by nerve injury and peripheral sensitization in HTMRs.
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Ungar OJ, Nadol JB, Faquin WC, Carey JP, Handzel O, Santos F. Histological characteristics of intra-temporal facial nerve paralysis in temporal bone malignancies. Laryngoscope 2020; 130:E358-E367. [PMID: 31369154 PMCID: PMC7425210 DOI: 10.1002/lary.28212] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Revised: 06/06/2019] [Accepted: 07/10/2019] [Indexed: 01/28/2023]
Abstract
OBJECTIVE To describe the histopathologic findings and clinical presentation of intra-temporal facial nerve invasion in primary and metastatic malignancies of the human temporal bone (TB). MATERIALS AND METHODS Retrospective analysis of all medical records of patients diagnosed with peripheral facial nerve palsy (PFnP) of a malignant origin was performed. Temporal bones underwent standard processing for histologic examination. Hematoxylin and eosin (H&E)-stained slides were examined by light microscopy. The histologic findings were compared to premortem clinical data. RESULTS Eighteen TBs were identified in 16 patients. The male to female ratio was 9:7. The median (range) age of death was 56.5 years (27 months to 75 years). The median time interval from facial nerve injury to death was 5.5 months. There were 11 carcinomas and seven sarcomas identified. Primary TB malignancies were identified in seven TBs (39%), and the rest (11 TBs, 61%) were of metastatic origin. Complete facial nerve paralysis (House-Brackmann [HB] grade VI), was the most common clinical presentation affecting nine patients (10 TBs, 56%). Neural involvement was multifocal in nature (16 of 18 TBs, 89%). The most commonly involved cranial nerve (CN) VII segment was the meatal segment (13 TBs, 72%), followed by the labyrinthine, tympanic, and vertical segments (nine, eight, and six TBs, respectively). CONCLUSION PFnP can be the result of local, regional, or distant malignancy, and is associated with poor survival. The facial nerve can serve as a route of tumor progression intracranially. Whereas every segment of CNV II can be violated by tumors, not all PFnP are related to direct tumor invasion. LEVEL OF EVIDENCE 4 Laryngoscope, 130:E358-E367, 2020.
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Affiliation(s)
- Omer J Ungar
- Department of Otolaryngology Head and Neck Surgery, Tel-Aviv Sourasky Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
- Department of Maxillofacial Surgery, Tel-Aviv Sourasky Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Joseph B Nadol
- Department of Otolaryngology, Massachusetts Eye and Ear, Boston, Massachusetts, U.S.A
- Department of Otolaryngology, Harvard Medical School, Boston, Massachusetts, U.S.A
| | - William C Faquin
- Department of Pathology, Massachusetts Eye and Ear, Boston, Massachusetts, U.S.A
- Massachusetts General Hospital, Boston, Massachusetts
- Harvard Medical School, Boston, Massachusetts, U.S.A
| | - John P Carey
- Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland, U.S.A
| | - Ophir Handzel
- Department of Otolaryngology Head and Neck Surgery, Tel-Aviv Sourasky Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
- Department of Maxillofacial Surgery, Tel-Aviv Sourasky Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Felipe Santos
- Department of Otolaryngology, Massachusetts Eye and Ear, Boston, Massachusetts, U.S.A
- Department of Otolaryngology, Harvard Medical School, Boston, Massachusetts, U.S.A
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13
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Israel Y, Rachmiel A, Gourevich K, Nagler R. Kaplan-Meier analysis of salivary gland tumors: prognosis and long-term survival. J Cancer Res Clin Oncol 2019; 145:2123-2130. [PMID: 31187201 DOI: 10.1007/s00432-019-02953-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2019] [Accepted: 06/07/2019] [Indexed: 02/07/2023]
Abstract
PURPOSE We evaluated the impact of various tumor related parameters on survival probability in a cohort of patients with malignant salivary tumors, using the Kaplan-Meier analysis. METHODS We measured patients up to 15 years following therapy, looking at T N M stage, grade perineural invasion and extra-parenchymal spread. RESULTS Of 101 patients diagnosed with various salivary malignant tumors in our medical center, 79 patients survived while 22 died with disease (DWD). The impact of distant metastasis (M+) was devastating (survival probability at 60 months and at 180 months dropped from 0.93 (M-) to 0.40 (M+) and from 0.67 to 0.40, respectively, p = 0.0001), the impact of perineural invasion was severe (at 180 months the probability of survival dropped from 0.75 to 0.21, p = 0.002). Higher stage tumor also decreased survival (from 0.82 to 0.53 at 180 months, p = 0.002) as did poor histological grade (from 0.85 to 0.48 at 180 months, p = 0.019). Neck metastasis (N+) impact was quite moderate (at 180 months the probability of survival dropped from 0.69 to 0.58, p = 0.044) while neither tumor size (T) nor extra-parenchymal spread significantly affected survival. CONCLUSIONS Salivary tumor location and its potential to infiltrate nerves and blood vessels and to metastasize is the most telling parameter. Systemic therapy aimed at halting distant metastatic spread is the most effective therapeutic goal. Dissection of N0 neck metastasis is not necessarily a valuable treatment.
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Affiliation(s)
- Yair Israel
- Department of Oral and Maxillofacial Surgery, Rambam Medical Center, Faculty of Medicine, Rappaport Family Institute for Research in the Medical Sciences, Technion-Israel Institute of Technology, 31096, Haifa, Israel
| | - Adi Rachmiel
- Department of Oral and Maxillofacial Surgery, Rambam Medical Center, Faculty of Medicine, Rappaport Family Institute for Research in the Medical Sciences, Technion-Israel Institute of Technology, 31096, Haifa, Israel
| | - Konstantin Gourevich
- Department of Nuclear Medicine, Rambam Medical Center, Faculty of Medicine, Rappaport Family Institute for Research in the Medical Sciences, Technion-Israel Institute of Technology, 31096, Haifa, Israel
| | - Rafael Nagler
- Department of Oral and Maxillofacial Surgery, Rambam Medical Center, Faculty of Medicine, Rappaport Family Institute for Research in the Medical Sciences, Technion-Israel Institute of Technology, 31096, Haifa, Israel.
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14
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Invasión perineural en el carcinoma epidermoide cutáneo. ACTAS DERMO-SIFILIOGRAFICAS 2019; 110:426-433. [DOI: 10.1016/j.ad.2018.10.006] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2018] [Revised: 09/29/2018] [Accepted: 10/01/2018] [Indexed: 02/06/2023] Open
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15
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Pérez García M, Mateu Puchades A, Sanmartín Jiménez O. Perineural Invasion in Cutaneous Squamous Cell Carcinoma. ACTAS DERMO-SIFILIOGRAFICAS 2019. [DOI: 10.1016/j.adengl.2019.05.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
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16
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Warner KA, Oklejas AE, Pearson AT, Zhang Z, Wu W, Divi V, Rodriguez-Ramirez C, Castilho RM, Polverini PJ, Nör JE. UM-HACC-2A: MYB-NFIB fusion-positive human adenoid cystic carcinoma cell line. Oral Oncol 2018; 87:21-28. [PMID: 30527239 DOI: 10.1016/j.oraloncology.2018.10.012] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2018] [Revised: 10/09/2018] [Accepted: 10/10/2018] [Indexed: 01/29/2023]
Abstract
OBJECTIVES Limited availability of validated human adenoid cystic carcinoma (ACC) cell lines has hindered the mechanistic understanding of the pathobiology of this malignancy and the development of effective therapies. The purpose of this work was to generate and characterize a human ACC cell line. MATERIAL AND METHODS Immediately after surgery, a tumor fragment from a minor salivary gland from the tongue of a female Caucasian was minced, dissociated, and a single cell suspension was plated in fibronectin-coated flasks. A culture medium containing bovine brain extract and rhEGF was optimized for these cells. Whole exome sequencing was used to evaluate the presence of MYB-NFIB translocation. RESULTS The University of Michigan-Human Adenoid Cystic Carcinoma (UM-HACC)-2A cells showed continuous growth in monolayers for at least 180 in vitro passages while maintaining epithelial morphology. Short-tandem repeat (STR) profiling confirmed a 100% match to patient DNA. Whole exome sequencing revealed the presence of the MYB-NFIB fusion in UM-HACC-2A cells, which was confirmed by PCR analysis. Western blots revealed high expression of epithelial markers (e.g. E-cadherin, EGFR, pan-cytokeratin) and proteins associated with ACC (e.g. c-Myb, p63). Developmental therapeutic studies showed that UM-HACC-2A cells were resistant to cisplatin (IC50 = 44.7 µM) while more responsive to paclitaxel (IC50 = 0.0006 µM). In a pilot study, we observed that UM-HACC-2A cells survived orthotopic transplantation into the submandibular gland. Notably, one of the mice injected with UM-HACC-2A cells exhibited lung metastasis after 6 months. CONCLUSION UM-HACC-2A is a MYB-NFIB fusion-positive ACC cell line that is suitable for mechanistic and developmental therapeutics studies.
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Affiliation(s)
- Kristy A Warner
- Department of Cariology, Restorative Sciences, Endodontics, University of Michigan School of Dentistry, Ann Arbor, MI 48109, USA
| | - Alexandra E Oklejas
- Department of Cariology, Restorative Sciences, Endodontics, University of Michigan School of Dentistry, Ann Arbor, MI 48109, USA
| | | | - Zhaocheng Zhang
- Department of Cariology, Restorative Sciences, Endodontics, University of Michigan School of Dentistry, Ann Arbor, MI 48109, USA
| | - Weishing Wu
- Biomedical Research Core Facility, University of Michigan, Ann Arbor, MI, USA
| | - Vasu Divi
- Department of Otolaryngology, Stanford University, Stanford, CA, USA
| | - Christie Rodriguez-Ramirez
- Department of Cariology, Restorative Sciences, Endodontics, University of Michigan School of Dentistry, Ann Arbor, MI 48109, USA
| | - Rogerio M Castilho
- Department of Periodontics and Oral Medicine, School of Dentistry, Ann Arbor, MI 48109, USA
| | - Peter J Polverini
- Department of Periodontics and Oral Medicine, School of Dentistry, Ann Arbor, MI 48109, USA
| | - Jacques E Nör
- Department of Cariology, Restorative Sciences, Endodontics, University of Michigan School of Dentistry, Ann Arbor, MI 48109, USA; Department of Biomedical Engineering, University of Michigan College of Engineering, Ann Arbor, MI, USA; Department of Otolaryngology, University of Michigan School of Medicine, Ann Arbor, MI, USA; Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA.
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Diagnostic accuracy of 18-F FDG-PET/CT in evaluation of malignant neuronal involvement in neurologically manifested cancer patients. THE EGYPTIAN JOURNAL OF RADIOLOGY AND NUCLEAR MEDICINE 2018. [DOI: 10.1016/j.ejrnm.2018.03.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
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18
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Schmitd LB, Beesley LJ, Russo N, Bellile EL, Inglehart RC, Liu M, Romanowicz G, Wolf GT, Taylor JMG, D'Silva NJ. Redefining Perineural Invasion: Integration of Biology With Clinical Outcome. Neoplasia 2018; 20:657-667. [PMID: 29800815 PMCID: PMC6030236 DOI: 10.1016/j.neo.2018.04.005] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2018] [Revised: 04/18/2018] [Accepted: 04/18/2018] [Indexed: 12/03/2022] Open
Abstract
A diagnosis of perineural invasion (PNI), defined as cancer within or surrounding at least 33% of the nerve, leads to selection of aggressive treatment in squamous cell carcinoma (SCC). Recent mechanistic studies show that cancer and nerves interact prior to physical contact. The purpose of this study was to explore cancer-nerve interactions relative to clinical outcome. Biopsy specimens from 71 patients with oral cavity SCC were stained with hematoxylin and eosin and immunohistochemical (IHC; cytokeratin, S100, GAP43, Tuj1) stains. Using current criteria, PNI detection was increased with IHC. Overall survival (OS) tended to be poor for patients with PNI (P = .098). OS was significantly lower for patients with minimum tumor-nerve distance smaller than 5 μm (P = .011). The estimated relative death rate decreased as the nerve-tumor distance increased; there was a gradual drop off in death rate from distance equal to zero that stabilized around 500 μm. In PNI-negative patients, nerve diameter was significantly related to OS (HR 2.88, 95%CI[1.11,7.49]). Among PNI-negative nerves, larger nerve-tumor distance and smaller nerve diameter were significantly related to better OS, even when adjusting for T-stage and age (HR 0.82, 95% CI[0.72,0.92]; HR 1.27, 95% CI[1.00,1.62], respectively). GAP43, a marker for neuronal outgrowth, stained less than Tuj1 in nerves at greater distances from tumor (OR 0.76, 95% CI[0.73,0.79]); more GAP43 staining was associated with PNI. Findings from a small group of patients suggest that nerve parameters other than presence of PNI can influence outcome and that current criteria of PNI need to be re-evaluated to integrate recent biological discoveries.
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Affiliation(s)
- Ligia B Schmitd
- Periodontics and Oral Medicine, University of Michigan School of Dentistry, 1011 N. University Ave, Ann Arbor, MI, USA
| | - Lauren J Beesley
- Biostatistics, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI, USA
| | - Nickole Russo
- Periodontics and Oral Medicine, University of Michigan School of Dentistry, 1011 N. University Ave, Ann Arbor, MI, USA
| | - Emily L Bellile
- Biostatistics, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI, USA
| | - Ronald C Inglehart
- Periodontics and Oral Medicine, University of Michigan School of Dentistry, 1011 N. University Ave, Ann Arbor, MI, USA
| | - Min Liu
- Periodontics and Oral Medicine, University of Michigan School of Dentistry, 1011 N. University Ave, Ann Arbor, MI, USA
| | - Genevieve Romanowicz
- Periodontics and Oral Medicine, University of Michigan School of Dentistry, 1011 N. University Ave, Ann Arbor, MI, USA
| | - Gregory T Wolf
- Otolaryngology, University of Michigan Medical School, 1500 E Medical Center Dr, Ann Arbor, MI, USA
| | - Jeremy M G Taylor
- Biostatistics, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI, USA
| | - Nisha J D'Silva
- Periodontics and Oral Medicine, University of Michigan School of Dentistry, 1011 N. University Ave, Ann Arbor, MI, USA;; Pathology, University of Michigan Medical School, 1500 E Medical Center Dr, Ann Arbor, MI, USA.
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19
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Solomon I, Voiculescu VM, Caruntu C, Lupu M, Popa A, Ilie MA, Albulescu R, Caruntu A, Tanase C, Constantin C, Neagu M, Boda D. Neuroendocrine Factors and Head and Neck Squamous Cell Carcinoma: An Affair to Remember. DISEASE MARKERS 2018; 2018:9787831. [PMID: 29854027 PMCID: PMC5966665 DOI: 10.1155/2018/9787831] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/27/2017] [Revised: 03/21/2018] [Accepted: 04/15/2018] [Indexed: 02/07/2023]
Abstract
Head and neck squamous cell carcinoma (HNSCC) is one of the most aggressive malignancies. Therefore, the major goal of cancer treatment is inhibition of tumor cell growth and of metastasis development. In order to choose the best management option for HNSCC patients, we need to identify reliable prognostic factors and to develop new molecular techniques in order to obtain a better understanding of therapy resistance. By acting as neurohormones, neurotransmitters, or neuromodulators, the neuroendocrine factors are able to signal the maintenance of physiological homeostasis or progression to malignant disease. Certain neuropeptides possess strong antitumor properties acting as tumor suppressors and immunomodulators, providing additional benefits for future potential therapeutic strategies. In light of the current understanding, cancer starts as a localized disease that can be effectively treated if discovered on proper time. Unfortunately, more than often cancer cells migrate to the surrounding tissues generating distant metastases, thus making the prognosis and survival in this stage much worse. As cellular migration is mandatory for tumor invasion and metastasis development, searching for alternate controllers of these processes, such as the neuroendocrine factors, it is an active tremendous task.
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Affiliation(s)
- Iulia Solomon
- Department of Dermatology and Allergology, Elias Emergency University Hospital, Bucharest, Romania
| | - Vlad Mihai Voiculescu
- Department of Dermatology and Allergology, Elias Emergency University Hospital, Bucharest, Romania
- Department of Dermatology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Constantin Caruntu
- Department of Physiology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- Department of Dermatology, “Prof. N. C. Paulescu” National Institute of Diabetes, Nutrition and Metabolic Diseases, Bucharest, Romania
| | - Mihai Lupu
- Department of Dermatology, MEDAS Titan Medical Center, Bucharest, Romania
| | - Alexandra Popa
- Department of Dermatology and Allergology, Elias Emergency University Hospital, Bucharest, Romania
| | - Mihaela Adriana Ilie
- Dermatology Research Laboratory, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- Department of Biochemistry, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Radu Albulescu
- Chemical and Pharmaceutical National Institute, Bucharest, Romania
| | - Ana Caruntu
- Department of Oral and Maxillofacial Surgery, Carol Davila Central Military Emergency Hospital, Bucharest, Romania
- Faculty of Medicine, Titu Maiorescu University, Bucharest, Romania
| | - Cristiana Tanase
- Faculty of Medicine, Titu Maiorescu University, Bucharest, Romania
- Victor Babes National Institute of Pathology, Bucharest, Romania
| | - Carolina Constantin
- Victor Babes National Institute of Pathology, Bucharest, Romania
- Colentina Clinical Hospital, Bucharest, Romania
| | - Monica Neagu
- Victor Babes National Institute of Pathology, Bucharest, Romania
- Colentina Clinical Hospital, Bucharest, Romania
- Faculty of Biology, University of Bucharest, Bucharest, Romania
| | - Daniel Boda
- Dermatology Research Laboratory, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
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20
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Rouchy RC, Attyé A, Medici M, Renard F, Kastler A, Grand S, Tropres I, Righini CA, Krainik A. Facial nerve tractography: A new tool for the detection of perineural spread in parotid cancers. Eur Radiol 2018; 28:3861-3871. [PMID: 29633003 DOI: 10.1007/s00330-018-5318-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2017] [Revised: 12/29/2017] [Accepted: 01/09/2018] [Indexed: 02/08/2023]
Abstract
OBJECTIVES To determine whether facial nerve MR tractography is useful in detecting PeriNeural Spread in parotid cancers. METHODS Forty-five participants were enrolled. Thirty patients with surgically managed parotid tumors (15 malignant, 15 benign) were compared with 15 healthy volunteers. All of them had undergone 3T-MRI with diffusion acquisition and post-processing constrained spherical deconvolution-based tractography. Parameters of diffusion-weighted sequences were b-value 1,000 s/mm2, 32 directions. Two radiologists performed a blinded visual reading of tractographic maps and graded the facial nerve average pathlength and fractional anisotropy (FA). We also compared diagnostic accuracy of tractography with morphological MRI sequences to detect PeriNeural Spread. Non-parametric methods were used. RESULTS Average pathlength was significantly higher in cases with PeriNeural Spread (39.86 mm [Quartile1: 36.27; Quartile3: 51.19]) versus cases without (16.23 mm [12.90; 24.90]), p<0.001. The threshold above which there was a significant association with PeriNeural Spread was set at 27.36 mm (Se: 100%; Sp: 84%; AUC: 0.96, 95% CI 0.904-1). There were no significant differences in FA between groups. Tractography map visual analyses directly displayed PeriNeural Spread in distal neural ramifications with sensitivity of 75%, versus 50% using morphological sequences. CONCLUSIONS Tractography could be used to identify facial nerve PeriNeural Spread by parotid cancers. KEY POINTS • Tractography could detect facial nerve PeriNeural Spread in parotid cancers. • The average pathlength parameter is increased in case of PeriNeural Spread. • Tractography could map PeriNeural Spread more precisely than conventional imaging.
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Affiliation(s)
- René-Charles Rouchy
- Department of Neuroradiology and MRI, Grenoble Alpes University Hospital - SFR RMN Neurosciences, F-38043, Grenoble, Cedex 9, France. .,University of Grenoble Alpes, IRMaGe, F-38000, Grenoble, France.
| | - Arnaud Attyé
- Department of Neuroradiology and MRI, Grenoble Alpes University Hospital - SFR RMN Neurosciences, F-38043, Grenoble, Cedex 9, France.,University of Grenoble Alpes, IRMaGe, F-38000, Grenoble, France
| | - Maud Medici
- Clinical Investigation Centre 1406 - Innovative Technology, National Institute of Health and Medical Research, Grenoble, France.,Public Health Department, Grenoble Alpes University Hospital, Grenoble, France
| | - Félix Renard
- University of Grenoble Alpes, IRMaGe, F-38000, Grenoble, France
| | - Adrian Kastler
- Department of Neuroradiology and MRI, Grenoble Alpes University Hospital - SFR RMN Neurosciences, F-38043, Grenoble, Cedex 9, France.,University of Grenoble Alpes, IRMaGe, F-38000, Grenoble, France
| | - Sylvie Grand
- Department of Neuroradiology and MRI, Grenoble Alpes University Hospital - SFR RMN Neurosciences, F-38043, Grenoble, Cedex 9, France.,University of Grenoble Alpes, IRMaGe, F-38000, Grenoble, France
| | - Irène Tropres
- University of Grenoble Alpes, IRMaGe, F-38000, Grenoble, France.,IRMaGe, Inserm US 17, CNRS UMS 3552, Grenoble, France
| | | | - Alexandre Krainik
- Department of Neuroradiology and MRI, Grenoble Alpes University Hospital - SFR RMN Neurosciences, F-38043, Grenoble, Cedex 9, France.,University of Grenoble Alpes, IRMaGe, F-38000, Grenoble, France
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21
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Yang X, Tian X, Wu K, Liu W, Li S, Zhang Z, Zhang C. Prognostic impact of perineural invasion in early stage oral tongue squamous cell carcinoma: Results from a prospective randomized trial. Surg Oncol 2018; 27:123-128. [PMID: 29937161 DOI: 10.1016/j.suronc.2018.02.005] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2017] [Revised: 01/23/2018] [Accepted: 02/12/2018] [Indexed: 12/25/2022]
Abstract
BACKGROUND Although perineural invasion (PNI) has been recognized as a poor prognostic factor for oral cancer, few studies have focused on tongue squamous cell carcinoma (TSCC). Using a prospective randomized trial, this study investigated the role of PNI in the regional control and survival of the patients with cT1-2N0 TSCC, and clarified the benefit of neck management based on PNI status. METHODS PNI status was reviewed under H&E staining in tumors of 221 patients with cT1-2N0 TSCC, who were randomly assigned into elective neck dissection (END) group (n = 111) and observation group (n = 110). Oncologic and survival outcomes were analyzed by multivariate regression and Kaplan-Meier analyses. RESULTS PNI was identified in 34 patients and multivariate analyses revealed that PNI remained an independent predictor for cervical lymph node metastasis (CLNM), local relapse, neck relapse and disease-specific survival (DSS) after controlling for T stage and pathologic differentiation. END could not improve the benefit for patients. Stratified analysis revealed that END also could not improve neck control or DSS among patients with PNI. CONCLUSIONS This study demonstrated that PNI was an invaluable pathological parameter to independently predict cervical metastasis, local relapse, neck relapse and poor survival outcomes, but END could not improve benefits compared to observation for the PNI-positive patients.
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Affiliation(s)
- Xi Yang
- Department of Oral & Maxillofacial-Head & Neck Oncology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, China; Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, China
| | - Xuerui Tian
- Department of Oral & Maxillofacial-Head & Neck Oncology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, China; Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, China
| | - Kailiu Wu
- Department of Oral & Maxillofacial-Head & Neck Oncology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, China; Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, China
| | - Wei Liu
- Department of Oral & Maxillofacial-Head & Neck Oncology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, China; Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, China
| | - Siyi Li
- Department of Oral & Maxillofacial-Head & Neck Oncology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, China; Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, China.
| | - Zhiyuan Zhang
- Department of Oral & Maxillofacial-Head & Neck Oncology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, China; Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, China.
| | - Chenping Zhang
- Department of Oral & Maxillofacial-Head & Neck Oncology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, China; Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, China.
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22
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Kirsch CF, Schmalfuss IM. Practical Tips for MR Imaging of Perineural Tumor Spread. Magn Reson Imaging Clin N Am 2018; 26:85-100. [DOI: 10.1016/j.mric.2017.08.006] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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23
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Huyett P, Duvvuri U, Ferris RL, Johnson JT, Schaitkin BM, Kim S. Perineural Invasion in Parotid Gland Malignancies. Otolaryngol Head Neck Surg 2018; 158:1035-1041. [PMID: 29337642 DOI: 10.1177/0194599817751888] [Citation(s) in RCA: 50] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Objectives To investigate the clinical predictors and survival implications of perineural invasion (PNI) in parotid gland malignancies. Study Design Case series with chart review. Setting Tertiary care medical center. Subjects and Methods Patients with parotid gland malignancies treated surgically from 2000 to 2015 were retrospectively identified in the Head and Neck Cancer Registry at a single institution. Data points were extracted from the medical record and original pathology reports. Results In total, 186 patients with parotid gland malignancies were identified with a mean follow-up of 5.2 years. Salivary duct carcinoma (45), mucoepidermoid carcinoma (44), and acinic cell carcinoma (26) were the most common histologic types. A total of 46.2% of tumors were found to have PNI. At the time of presentation, facial nerve paresis (odds ratio [OR], 64.7; P < .001) and facial pain (OR, 3.7; P = .002) but not facial paresthesia or anesthesia (OR, 2.8, P = .085) were predictive of PNI. Malignancies with PNI were significantly more likely to be of advanced T and N classification, be high-risk pathologic types, and have positive margins and angiolymphatic invasion. PNI positivity was associated with worse overall (hazard ratio, 2.62; P = .001) and disease-free survival (4.18; P < .001) on univariate Cox regression analysis. However, when controlling for other negative prognosticators, age, and adjuvant therapy, PNI did not have a statistically significant effect on disease-free or overall survival. Conclusions PNI is strongly correlated with more aggressive parotid gland malignancies but is not an independent predictor of worse survival. Facial paresis and pain were predictive of PNI positivity, and facial paresis correlated with worse overall and disease-free survival.
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Affiliation(s)
- Phillip Huyett
- 1 Department of Otolaryngology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Umamaheswar Duvvuri
- 1 Department of Otolaryngology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Robert L Ferris
- 1 Department of Otolaryngology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Jonas T Johnson
- 1 Department of Otolaryngology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Barry M Schaitkin
- 1 Department of Otolaryngology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Seungwon Kim
- 1 Department of Otolaryngology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
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Dercle L, Hartl D, Rozenblum-Beddok L, Mokrane FZ, Seban RD, Yeh R, Bidault F, Ammari S. Diagnostic and prognostic value of 18F-FDG PET, CT, and MRI in perineural spread of head and neck malignancies. Eur Radiol 2017; 28:1761-1770. [PMID: 29086023 DOI: 10.1007/s00330-017-5063-x] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2017] [Revised: 08/15/2017] [Accepted: 09/06/2017] [Indexed: 12/16/2022]
Abstract
OBJECTIVES We assessed whether quantitative imaging biomarkers derived from fluorodeoxyglucose-positron emission tomography (18F-FDG PET) could be extracted from perineural spread (PNS) in head and neck malignancies (HNM) to improve patient risk stratification. METHODS A case-control exploratory study (1:2 ratio) enrolled 81 patients with FDG-avid HNM. The case-group comprised 28 patients with documented PNS (reference: expert consensus), including 14 squamous cell carcinomas (SCC). Imaging biomarkers were extracted from the PNS on 18F-FDG PET, CT-scan, and MRI. The control-group enrolled 53 SCCs. The Cox proportional-hazards regression model explored the association with overall survival by univariate and multivariate analyses. RESULTS The rate of PNS detection by 18F-FDG PET was 100% in the case-group. Quantitative imaging biomarkers were not associated with the presence of sensory (p>0.20) or motor (p>0.10) symptoms. In SCC patients (case: 14; control: 53), PNS was associated with a hazard ratio of death of 5.5 (95%CI: 1.4:20.9) by multivariate analysis. Increased cranial nerve SUVmax was significantly associated with poorer overall survival by univariate analysis (p=0.001). CONCLUSIONS Our pilot study showed the feasibility of extracting 18F-FDG PET biomarkers from PNS in FDG-avid HNM. Our results encourage the development of new PET/CT- or PET/MRI-guided management strategies in further prospective studies. KEY POINTS • 18F-FDG PET/CT detects PNS in FDG-avid HNM. • PNS metabolism is more heterogeneous than healthy tissue. • PNS diagnosis is crucial: most patients were asymptomatic, N0 and M0. • PNS diagnosis is associated with poorer overall survival in SCC. • PET/CT- or PET/MRI-guided management strategies should be evaluated.
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Affiliation(s)
- Laurent Dercle
- Département d'imagerie médicale, Institut Gustave-Roussy, 94805, Villejuif, France. .,UMR1015, Institut Gustave Roussy, 94800, Villejuif, France. .,Department of Radiology, New York Presbyterian Hospital, Columbia University Medical Center, New York, NY, 10039, USA.
| | - Dana Hartl
- Département d'oto-rhino-laryngologie, Institut Gustave-Roussy, 94805, Villejuif, France
| | | | - Fatima-Zohra Mokrane
- Radiology department, Rangueil University Hospital, 1 avenue du Professeur Jean Poulhes. 31059 CEDEX, Toulouse, France.,French National Center for Scientific Research, AMIS Laboratory: University of Toulouse, UMR 5288, 37 allées Jules Guesde, 31073, Toulouse, France
| | - Romain-David Seban
- Département d'imagerie médicale, Institut Gustave-Roussy, 94805, Villejuif, France
| | - Randy Yeh
- Department of Radiology, New York Presbyterian Hospital, Columbia University Medical Center, New York, NY, 10039, USA
| | - François Bidault
- Département d'imagerie médicale, Institut Gustave-Roussy, 94805, Villejuif, France
| | - Samy Ammari
- Département d'imagerie médicale, Institut Gustave-Roussy, 94805, Villejuif, France
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Barbiero FJ, Huttner AJ, Judson BL, Baehring JM. Leiomyosarcoma of the infratemporal fossa with perineurial spread along the right mandibular nerve: a case report. CNS Oncol 2017; 6:281-285. [PMID: 28990793 DOI: 10.2217/cns-2017-0004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Leiomyosarcomas are malignant tumors displaying strong smooth muscle differentiation. They can often develop within the GI tract and myometrium, but are particularly rare in the head and neck. Perineurial spread of head and neck cancer is observed in patients with neoplasms of the skin (squamous cell carcinoma, melanoma) or skin appendages (adenoid cystic carcinoma). We report the case of a woman who presented with diplopia and headaches. MRI showed an infratemporal mass lesion and faint enhancement tracking along the mandibular nerve into the wall of the right cavernous sinus. A nerve biopsy revealed leiomyosarcoma. We review the medical literature to provide further insight into the diagnosis and management of this tumor and its peculiar pattern of spread. A similar case was unidentifiable in the literature.
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Affiliation(s)
- Frank J Barbiero
- Department of Neurology, Yale School of Medicine, New Haven, CT 06510, USA
| | - Anita J Huttner
- Department of Pathology, Yale School of Medicine, New Haven, CT 06520, USA
| | - Benjamin L Judson
- Department of Surgery, Otolaryngology, Yale School of Medicine, New Haven, CT 06520, USA
| | - Joachim M Baehring
- Department of Neurology, Yale School of Medicine, New Haven, CT 06510, USA.,Department of Neurosurgery, Yale School of Medicine, New Haven, CT 06520, USA
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Tianyi L, Zhiyuan S. [Role of CCL5/CCR5 in the perineural invasion of salivary adenoid cystic carcinoma cells]. HUA XI KOU QIANG YI XUE ZA ZHI = HUAXI KOUQIANG YIXUE ZAZHI = WEST CHINA JOURNAL OF STOMATOLOGY 2017; 35:479-483. [PMID: 29188641 DOI: 10.7518/hxkq.2017.05.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
OBJECTIVE This study aimed the role of the CCL5/CCR5 axis in the perineural invasion of salivary adenoid cystic carcinoma (SACC) cells. METHODS Immunohistochemical analysis and flow cytometric analysis were conducted to detect the expression of the chemokine receptor CCR5 in SACC cells. Enzyme linked immunosorbent assay (ELISA) was performed to determine the expression of CCL5 in the supernate of human nerve cells. The flow cytometric analysis was applied to observe the changes in F-actin in SACC-LM cells, which were pretreated with CCL5. To assess the effects of the CCL5/CCR5 axis on the migration and invasion of SACC-LM cells, we performed a scratch test and invasion assay under CCL5 stimulation. RESULTS CCR5 was highly expressed in SACC cells. The concentration of CCL5 in the supernatant of human nerve cells was (359.2±15.8), (696.4±22.6) pg·mL⁻¹. The CCL5/CCR5 axis promoted the migration and invasion of SACC-LM cells. CONCLUSIONS The CCL5/CCR5 axis may be involved in the perineural invasion of SACC cells.
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Affiliation(s)
- Li Tianyi
- Dept. of Pediatric Dentistry, Stomatological Hospital of Shandong University, Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan 250012, China
| | - Shen Zhiyuan
- Dept. of Oral and Maxillofacial Surgery, Stomatological Hospital of Shandong University, Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan 250012, China
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Ban K, Feng S, Shao L, Ittmann M. RET Signaling in Prostate Cancer. Clin Cancer Res 2017; 23:4885-4896. [PMID: 28490466 DOI: 10.1158/1078-0432.ccr-17-0528] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2017] [Revised: 04/24/2017] [Accepted: 05/04/2017] [Indexed: 12/14/2022]
Abstract
Purpose: Large diameter perineural prostate cancer is associated with poor outcomes. GDNF, with its coreceptor GFRα1, binds RET and activates downstream pro-oncogenic signaling. Because both GDNF and GFRα1 are secreted by nerves, we examined the role of RET signaling in prostate cancer.Experimental Design: Expression of RET, GDNF, and/or GFRα1 was assessed. The impact of RET signaling on proliferation, invasion and soft agar colony formation, perineural invasion, and growth in vivo was determined. Cellular signaling downstream of RET was examined by Western blotting.Results: RET is expressed in all prostate cancer cell lines. GFRα1 is only expressed in 22Rv1 cells, which is the only line that responds to exogenous GDNF. In contrast, all cell lines respond to GDNF plus GFRα1. Conditioned medium from dorsal root ganglia contains secreted GFRα1 and promotes transformation-related phenotypes, which can be blocked by anti-GFRα1 antibody. Perineural invasion in the dorsal root ganglion assay is inhibited by anti-GFRα antibody and RET knockdown. In vivo, knockdown of RET inhibits tumor growth. RET signaling activates ERK or AKT signaling depending on context, but phosphorylation of p70S6 kinase is markedly increased in all cases. Knockdown of p70S6 kinase markedly decreases RET induced transformed phenotypes. Finally, RET is expressed in 18% of adenocarcinomas and all three small-cell carcinomas examined.Conclusions: RET promotes transformation associated phenotypes, including perineural invasion in prostate cancer via activation of p70S6 kinase. GFRα1, which is secreted by nerves, is a limiting factor for RET signaling, creating a perineural niche where RET signaling can occur. Clin Cancer Res; 23(16); 4885-96. ©2017 AACR.
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Affiliation(s)
- Kechen Ban
- Department of Pathology & Immunology, Baylor College of Medicine and Michael E. DeBakey Dept. of Veterans Affairs Medical Center, Houston, Texas
| | - Shu Feng
- Department of Pathology & Immunology, Baylor College of Medicine and Michael E. DeBakey Dept. of Veterans Affairs Medical Center, Houston, Texas
| | - Longjiang Shao
- Department of Pathology & Immunology, Baylor College of Medicine and Michael E. DeBakey Dept. of Veterans Affairs Medical Center, Houston, Texas
| | - Michael Ittmann
- Department of Pathology & Immunology, Baylor College of Medicine and Michael E. DeBakey Dept. of Veterans Affairs Medical Center, Houston, Texas.
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Keller G, Steinmann D, Quaas A, Grünwald V, Janssen S, Hussein K. New concepts of personalized therapy in salivary gland carcinomas. Oral Oncol 2017; 68:103-113. [PMID: 28325631 DOI: 10.1016/j.oraloncology.2017.02.018] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2016] [Revised: 01/18/2017] [Accepted: 02/20/2017] [Indexed: 12/13/2022]
Abstract
Salivary gland carcinomas are rare tumours and therapy strategies are less standardized than in lung, gastric or breast cancer. Therapy is based on surgery, but not all carcinomas are completely resectable, e.g. because carcinomas often show infiltration of nerves. For further therapy decision pathology is recommended, but evaluation of potential targets for personalized therapy is not part of the routine panel. Many salivary gland carcinomas can be resistant to radio- and/or chemotherapy, which limits therapeutic options. This review summarizes new concepts for personalized therapy in salivary gland carcinoma patients. Targeting growth receptors HER2, EGFR, AR and ER is possible but, in some studies, potential target molecules were not adequately tested before therapy. In addition, approximately 20-25% of carcinomas have RAS mutation (mainly H-RAS), which could explain resistance to therapy. Possible therapy options in the future could be immunomodulation (inhibition of PDL1/PD1 signalling), nanoparticles (gold nanoparticles conjugated to cetuximab can increase radiosensitivity) and drug delivery systems (trastuzumab emtansine/T-DM1).
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Affiliation(s)
- Gunter Keller
- Institute of Pathology, Hannover Medical School (MHH), Hannover, Germany; Department of Cranio-Maxillo-Facial Surgery, Henriettenstift, Hannover, Germany
| | - Diana Steinmann
- Institute for Radiation Therapy and Special Oncology, Hannover Medical School (MHH), Hannover, Germany
| | - Alexander Quaas
- Institute of Pathology, University Hospital Cologne, Cologne, Germany
| | - Viktor Grünwald
- Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School (MHH), Hannover, Germany
| | | | - Kais Hussein
- Institute of Pathology, Hannover Medical School (MHH), Hannover, Germany.
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Romero-Reyes M, Salvemini D. Cancer and orofacial pain. Med Oral Patol Oral Cir Bucal 2016; 21:e665-e671. [PMID: 27694791 PMCID: PMC5116107 DOI: 10.4317/medoral.21515] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2016] [Accepted: 08/05/2016] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Cancer pain is a devastating condition. Pain in the orofacial region, may be present as the single symptom of cancer or as a symptom of cancer in its later stages. This manuscript revises in a comprehensive manner the content of the conference entitled "Orofacial Pain and Cancer" (Dolor Orofacial y Cancer) given at the VI Simposio International "Advances in Oral Cancer" on the 22 July, 2016 in San Sebastioan-Donostia, Spain. MATERIAL AND METHODS We have reviewed (pubmed-medline) from the most relevant literature including reviews, systematic reviews and clinical cases, the significant and evidence-based mechanisms and mediators of cancer-associated facial pain, the diverse types of cancers that can be present in the craniofacial region locally or from distant sites that can refer to the orofacial region, cancer therapy that may induce pain in the orofacial region as well as discussed some of the new advancements in cancer pain therapy. RESULTS There is still a lack of understanding of cancer pain pathophysiology since depends of the intrinsic heterogeneity, type and anatomic location that the cancer may present, making more challenging the creation of better therapeutic options. Orofacial pain can arise from regional or distant tumor effects or as a consequence of cancer therapy. CONCLUSIONS The clinician needs to be aware that the pain may present the characteristics of any other orofacial pain disorder so a careful differential diagnosis needs to be given. Cancer pain diagnosis is made by exclusion and only can be reached after a thorough medical history, and all the common etiologies have been carefully investigated and ruled out. The current management tools are not optimal but there is hope for new, safer and effective therapies coming in the next years.
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Affiliation(s)
- M Romero-Reyes
- Department of Oral & Maxillofacial, Pathology, Radiology & Medicine, New York University College of Dentistry, 345 East 24th Street, New York, NY 10010,
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Markowski MC, Wobker SE, Strowd RE, Antonarakis ES. Lumbosacral Plexus Involvement as the First Site of Metastatic Recurrence in a Patient With CTNNB1-Mutant Prostate Cancer. Clin Genitourin Cancer 2016; 14:e417-22. [PMID: 26992487 PMCID: PMC9774045 DOI: 10.1016/j.clgc.2016.02.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2016] [Revised: 02/05/2016] [Accepted: 02/14/2016] [Indexed: 12/24/2022]
Affiliation(s)
| | - Sara E. Wobker
- Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD
| | - Roy E. Strowd
- Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD
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Wei YS, Yao DS, Long Y. Evaluation of the association between perineural invasion and clinical and histopathological features of cervical cancer. Mol Clin Oncol 2016; 5:307-311. [PMID: 27588197 DOI: 10.3892/mco.2016.941] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2016] [Accepted: 05/24/2016] [Indexed: 01/06/2023] Open
Abstract
Perineural invasion (PNI) has been investigated as a new prognostic factor in a number of carcinomas. However, studies on PNI in cervical cancer are limited, and inconsistent conclusions have been reported by different groups. The aim of the present study was to analyze the relationship between perineural invasion (PNI) and clinical and histopathological features of cervical cancer, and to evaluate the clinical significance of PNI of cervical cancer. Retrospective review identified 206 patients with cervical cancer who underwent radical hysterectomy plus pelvic lymphadenectomy between December 2012 and August 2014. The association between PNI and clinical and histopathological features of cervical cancer and post-operative radiotherapy was evaluated based on univariate and multivariate analyses. PNI of cervical cancer was identified in 33 of 206 (16%) cervical cancer patients. Univariate analysis demonstrated that PNI was associated with clinical stage, tumor grade, tumor size, depth of invasion, lymphovascular space invasion (LVSI), and lymph node metastasis (P<0.05), but not associated with age and histopathological types (P>0.05). Multivariate analysis suggests that LVSI and lymph node metastasis were associated with PNI of cervical cancer (P<0.05). In addition, post-operative radiotherapy was significantly more recommended for patients with PNI than those without PNI (P<0.001). In conclusion, PNI of cervical cancer is associated with LVSI and lymph node metastasis and can be used as an index for the determination of post-operative radiotherapy for cervical cancer patients.
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Affiliation(s)
- You-Sheng Wei
- Department of Gynecologic Oncology, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - De-Sheng Yao
- Department of Gynecologic Oncology, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Ying Long
- Department of Gynecologic Oncology, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
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Interobserver Variation Among Pathologists in Evaluating Perineural Invasion for Oral Squamous Cell Carcinoma. Head Neck Pathol 2016; 10:451-464. [PMID: 27140176 PMCID: PMC5082046 DOI: 10.1007/s12105-016-0722-9] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2016] [Accepted: 04/27/2016] [Indexed: 01/28/2023]
Abstract
The aims of this study are as follows: (1) to assess variations among pathologists in evaluating perineural invasion (PNI) in oral squamous cell carcinoma (OSCC), (2) to survey PNI criteria used by pathologists and how they came to adopt those criteria. An electronic survey was sent to 363 oral and/or surgical pathologists. Eligibility criteria included pathology board certification. The survey participants were asked to rate whether PNI was present, absent, or uncertain for 15 provided photomicrographs, which depicted various types of tumor-nerve relationships without excessive desmoplasia or lymphocytic host response. The survey obtained information regarding demographics, whether PNI criteria were taught during residency, criteria used by participants to evaluate PNI, how the participants developed their criteria, and agreement with six proposed PNI definitions. 88 pathologists completed the survey. The participants included 47 males and 41 females, with average age = 49 years and average practice experience = 17 years. Practice settings included dental school (40 %), medical school (36 %), private pathology lab (13 %), and other (11 %). Agreement between participants in rating PNI status for the provided images was fair (κ = .38, 95 % CI .37-.39). 56 % of respondents indicated that they were taught PNI criteria during residency training. The basis for criteria currently used by participants included residency training (n = 42), published literature (n = 29), and own experience/views (n = 32). Agreement regarding six proposed PNI definitions was slight (κ = .10, 95 % CI .08-.11). In conclusion, interobserver agreement in assessing PNI status was fair. Our results suggest that more widely accepted, objective, and reproducible criteria are needed for evaluating PNI in OSCC.
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Abstract
Orofacial pain may be a symptom of diverse types of cancers as a result of local or distant tumor effects. The pain can be presented with the same characteristics as any other orofacial pain disorder, and this should be recognized by the clinician. Orofacial pain also can arise as a consequence of cancer therapy. In the present article, we review the mechanisms of cancer-associated facial pain, its clinical presentation, and cancer therapy associated with orofacial pain.
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Affiliation(s)
- Marcela Romero-Reyes
- Orofacial and Head Pain Service, Department of Oral and Maxillofacial Pathology Radiology and Medicine, New York University College of Dentistry, 345 East 24th Street, New York, NY, 10010, USA,
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Erkan S, Acharya AN, Savundra J, Lewis SB, Rajan GP. En Bloc Resection of Desmoplastic Neurotropic Melanoma with Perineural Invasion of the Intracranial Trigeminal and Intraparotid Facial Nerve: Case Report and Review of the Literature. J Neurol Surg Rep 2016; 77:e008-12. [PMID: 26929895 PMCID: PMC4726377 DOI: 10.1055/s-0035-1566254] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2015] [Accepted: 09/14/2015] [Indexed: 12/31/2022] Open
Abstract
Background Desmoplastic neurotropic melanoma (DNM) is a rare, highly malignant, and locally invasive form of cutaneous melanoma with a tendency for perineural invasion (PNI). Methods We report a case of a 61-year-old man presenting with right-sided trigeminal neuralgia and progressive facial paresis due to the PNI of the intracranial trigeminal nerve and the intraparotid facial nerve from DNM. We also present a review of the literature with six cases of DNM with PNI of the intracranial trigeminal nerve identified. Results The combined transtemporal-infratemporal fossa approach was performed to achieve total en bloc resection of the tumor mass followed by postoperative radiotherapy (PORT). After 24 months of follow-up, the patient remains disease free with no signs of recurrence on magnetic resonance imaging. Conclusion We recommend the en bloc resection of the tumor mass followed by PORT for the management of DNM with PNI. A high index of suspicion for PNI as a cause of cranial neuropathies is essential for the early detection and treatment of patients with known melanoma.
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Affiliation(s)
- Serkan Erkan
- Department of Otolaryngology, Head and Surgery, Fiona Stanley Hospital, Murdoch, Western Australia, Australia
| | - Aanand N Acharya
- Department of Otolaryngology, Head and Surgery, Fiona Stanley Hospital, Murdoch, Western Australia, Australia
| | - James Savundra
- Department of Plastics Surgery, Royal Perth Hospital, Perth, Western Australia, Australia
| | - Stephen B Lewis
- Perth Neurosurgery, Hollywood Medical Centre, Nedlands, Western Australia, Australia
| | - Gunesh P Rajan
- Department of Otolaryngology, Head and Surgery, Fiona Stanley Hospital, Murdoch, Western Australia, Australia; Skull Base Division, Otolaryngology, Head and Neck Surgery, University of Western Australia, Murdoch, Western Australia, Australia
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Abstract
The perineural space is a compartment located between the nerve axons, supporting cells and tissues, and the epineural fibrous sheath. Tumor cells invade this space in response to a complex interplay of trophic factors in the local microenviroment. This attraction of tumor cells to nerves is referred to as neurotropism. The perineural space provides a conduit for tumor spread beyond the primary site of tumor occurrence. Perineural tumor growth is of two types: perineural invasion, affecting small unnamed nerves; and perineural spread, affecting larger, named nerves and presenting with clinical symptoms related to the involved nerve. Both forms of perineural tumor growth represent an adverse prognostic feature and are an essential element of the histopathologic reporting of malignancies of the head and neck region. Perineural spread is associated with decreased overall survival. Endoneurial invasion frequently accompanies perineural spread. The epineurium is more resistant to invasion and represents an important barrier to tumor spread. Immunohistochemical stains such as broad-spectrum keratin can aid in defining the proximal extent of perineural tumor spread.
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Affiliation(s)
- Ian S Brown
- Department of Anatomical Pathology, Envoi specialist Pathologists, Brisbane, Queensland, Australia; Department of Anatomical Pathology, Anatomical Pathology, Pathology Queensland, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia
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Johnston ML, Huang SH, Waldron JN, Atenafu EG, Chan K, Cummings BJ, Gilbert RW, Goldstein D, Gullane PJ, Irish JC, Perez-Ordonez B, Weinreb I, Bayley A, Cho J, Dawson LA, Hope A, Ringash J, Witterick IJ, O'Sullivan B, Kim J. Salivary duct carcinoma: Treatment, outcomes, and patterns of failure. Head Neck 2015; 38 Suppl 1:E820-6. [PMID: 25916947 DOI: 10.1002/hed.24107] [Citation(s) in RCA: 71] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/16/2015] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND Salivary duct carcinoma is rare, with distinct morphology and behavior. We reviewed our institutional experience with salivary duct carcinoma, aiming to characterize clinical behavior and treatment outcomes. METHODS All salivary duct carcinomas treated curatively between 1999 and 2010 were reviewed. Overall survival (OS), locoregional control, distant control, and patterns of failure were analyzed. Multivariate analysis identified predictors of OS. RESULTS Fifty-four patients with salivary duct carcinoma (parotid gland = 49; submandibular gland = 5) were included in the analysis. Fifty-three patients underwent primary surgery, and 48 (89%) received postoperative radiotherapy (RT; median dose = 60 Gy). Median follow-up was 5.7 years. The 5-year OS, locoregional control, and distant control were 43%, 70%, and 48%, respectively. Nine local (6 involving facial nerve), 10 regional, and 28 distant failures were identified. Multiple pathologic involved lymph nodes (pN2b/N2c) predicted reduced OS (hazard ratio [HR] = 3.6; p = .02). CONCLUSION Distant recurrence is common. Presence of pN2b/N2c disease is associated with reduced OS. Local recurrence frequently involves the facial nerves. © 2015 Wiley Periodicals, Inc. Head Neck 38: E820-E826, 2016.
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Affiliation(s)
- Meredith L Johnston
- Radiation Medicine Program, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - Shao Hui Huang
- Radiation Medicine Program, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - John N Waldron
- Radiation Medicine Program, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - Eshetu G Atenafu
- Department of Biostatistics, University Health Network, Princess Margaret Cancer Centre, Toronto, Ontario, Canada
| | - Kelvin Chan
- Department of Medical Oncology Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - Bernard J Cummings
- Radiation Medicine Program, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - Ralph W Gilbert
- Department of Otolaryngology - Head and Neck Surgery/Surgical Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - David Goldstein
- Department of Otolaryngology - Head and Neck Surgery/Surgical Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - Patrick J Gullane
- Department of Otolaryngology - Head and Neck Surgery/Surgical Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - Jonathan C Irish
- Department of Otolaryngology - Head and Neck Surgery/Surgical Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | | | - Ilan Weinreb
- Department of Pathology, University Health Network, Toronto, Ontario, Canada
| | - Andrew Bayley
- Radiation Medicine Program, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - John Cho
- Radiation Medicine Program, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - Laura A Dawson
- Radiation Medicine Program, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - Andrew Hope
- Radiation Medicine Program, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - Jolie Ringash
- Radiation Medicine Program, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - Ian J Witterick
- Department of Otolaryngology - Head and Neck Surgery/Surgical Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - Brian O'Sullivan
- Radiation Medicine Program, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - John Kim
- Radiation Medicine Program, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
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Scanlon CS, Banerjee R, Inglehart RC, Liu M, Russo N, Hariharan A, van Tubergen EA, Corson SL, Asangani IA, Mistretta CM, Chinnaiyan AM, D'Silva NJ. Galanin modulates the neural niche to favour perineural invasion in head and neck cancer. Nat Commun 2015; 6:6885. [PMID: 25917569 PMCID: PMC4476386 DOI: 10.1038/ncomms7885] [Citation(s) in RCA: 77] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2014] [Accepted: 03/09/2015] [Indexed: 02/07/2023] Open
Abstract
Perineural invasion (PNI) is an indicator of poor survival in multiple cancers. Unfortunately, there is no targeted treatment for PNI since the molecular mechanisms are largely unknown. PNI is an active process, suggesting that cancer cells communicate with nerves. However, nerve-tumour crosstalk is understudied due to the lack of in vivo models to investigate the mechanisms. Here, we developed an in vivo model of PNI to characterise this interaction. We show that the neuropeptide galanin (GAL) initiates nerve-tumour crosstalk via activation of its G-protein-coupled receptor, GALR2. Our data reveal a novel mechanism by which GAL from nerves stimulates GALR2 on cancer cells to induce NFATC2-mediated transcription of cyclooxygenase-2 and GAL. Prostaglandin E2 promotes cancer invasion, and in a feedback mechanism, GAL released by cancer induces neuritogenesis, facilitating PNI. This study describes a novel in vivo model for PNI and reveals the dynamic interaction between nerve and cancer.
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Affiliation(s)
- Christina Springstead Scanlon
- Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, Michigan 48109, USA
| | - Rajat Banerjee
- Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, Michigan 48109, USA
| | - Ronald C Inglehart
- Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, Michigan 48109, USA
| | - Min Liu
- Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, Michigan 48109, USA
| | - Nickole Russo
- Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, Michigan 48109, USA
| | - Amirtha Hariharan
- Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, Michigan 48109, USA
| | - Elizabeth A van Tubergen
- Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, Michigan 48109, USA
| | - Sara L Corson
- Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, Michigan 48109, USA
| | - Irfan A Asangani
- 1] Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [2] Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [3] Department of Urology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
| | - Charlotte M Mistretta
- Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, Michigan 48109, USA
| | - Arul M Chinnaiyan
- 1] Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [2] Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [3] Department of Urology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
| | - Nisha J D'Silva
- 1] Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, Michigan 48109, USA [2] Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [3] Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
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Gupta A, Veness M, De'Ambrosis B, Selva D, Huilgol SC. Management of squamous cell and basal cell carcinomas of the head and neck with perineural invasion. Australas J Dermatol 2015; 57:3-13. [PMID: 25759949 DOI: 10.1111/ajd.12314] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2014] [Accepted: 12/16/2014] [Indexed: 01/01/2023]
Abstract
Perineural invasion (PNI) occurring in non-melanoma skin cancers (NMSC) is associated with an increased risk of locoregional recurrence and reduced disease-free survival. This necessitates early and accurate diagnosis, appropriate risk-stratification and a clear management strategy. The diagnosis of PNI is based on careful clinical assessment, imaging and histopathology. Surgery, preferably with margin control, and definitive or adjuvant radiotherapy (ART) are established treatment strategies for PNI. Clinical uncertainty remains over the role of ART in incidental PNI. This review synthesises current literature to ascertain which clinicopathological features impart a higher risk to individuals with PNI in NMSC, in order to provide treatment algorithms, including the identification of patient subsets that are most likely to benefit from ART. This includes those with extratumoural PNI, involvement of larger-calibre nerves, tumour invasion beyond dermis, recurrent tumour or diffuse intratumoural spread. Patients with clinical PNI may be optimally managed by a multidisciplinary head and neck cancer service that is best placed to offer skull base surgery and intensity-modulated radiation therapy (IMRT). The management options presented are stratified by histological subtype and a new classification of PNI into low-risk, medium-risk and high-risk groups.
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Affiliation(s)
- Aakriti Gupta
- Department of Dermatology, University of Adelaide, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Michael Veness
- Westmead Cancer Care Centre, University of Sydney, Sydney, New South Wales, Australia
| | - Brian De'Ambrosis
- University of Queensland and South East Dermatology, Brisbane, Queensland, Australia
| | - Dinesh Selva
- Department of Ophthalmology & Visual Sciences, University of Adelaide and South Australian Institute of Ophthalmology, Adelaide, South Australia, Australia.,Adelaide Skin and Eye Centre, Adelaide, South Australia, Australia
| | - Shyamala C Huilgol
- Department of Dermatology, University of Adelaide, Royal Adelaide Hospital, Adelaide, South Australia, Australia.,Adelaide Skin and Eye Centre, Adelaide, South Australia, Australia
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He S, He S, Chen CH, Deborde S, Bakst RL, Chernichenko N, McNamara WF, Lee SY, Barajas F, Yu Z, Al-Ahmadie HA, Wong RJ. The chemokine (CCL2-CCR2) signaling axis mediates perineural invasion. Mol Cancer Res 2014; 13:380-90. [PMID: 25312961 DOI: 10.1158/1541-7786.mcr-14-0303] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
UNLABELLED Perineural invasion is a form of cancer progression where cancer cells invade along nerves. This behavior is associated with poor clinical outcomes; therefore, it is critical to identify novel ligand-receptor interactions between nerves and cancer cells that support the process of perineural invasion. A proteomic profiler chemokine array was used to screen for nerve-derived factors secreted from tissue explants of dorsal root ganglion (DRG), and CCL2 was identified as a lead candidate. Prostate cancer cell line expression of CCR2, the receptor to CCL2, correlated closely with MAPK and Akt pathway activity and cell migration towards CCL2 and DRG. In vitro nerve and cancer coculture invasion assays of perineural invasion demonstrated that cancer cell CCR2 expression facilitates perineural invasion. Perineural invasion is significantly diminished in coculture assays when using DRG harvested from CCL2(-/-) knockout mice as compared with control CCL2(+/+) mice, indicating that CCR2 is required for perineural invasion in this murine model of perineural invasion. Furthermore, 20 of 21 (95%) patient specimens of prostate adenocarcinoma with perineural invasion exhibited CCR2 expression by immunohistochemistry, while just 3 of 13 (23%) lacking perineural invasion expressed CCR2. In summary, nerve-released CCL2 supports prostate cancer migration and perineural invasion though CCR2-mediated signaling. IMPLICATIONS These results reveal CCL2-CCR2 signaling as a key ligand-receptor mechanism that mediates cancer cell communication with nerves during perineural invasion and highlight a potential future therapeutic target.
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Affiliation(s)
- Shizhi He
- Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York. Department of Otolaryngology-Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, PR China
| | - Shuangba He
- Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York. Department of Otolaryngology-Head and Neck Surgery, Anhui Provincial Hospital, Anhui Medical University, Anhui, China
| | - Chun-Hao Chen
- Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York
| | - Sylvie Deborde
- Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York
| | - Richard L Bakst
- Department of Radiation Oncology, Mount Sinai Hospital, New York, New York
| | - Natalya Chernichenko
- Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York
| | - William F McNamara
- Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York
| | - Sei Young Lee
- Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York
| | - Fernando Barajas
- Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York
| | - Zhenkun Yu
- Department of Otolaryngology-Head and Neck Surgery, Nanjing Tongren Hospital, Nanjing, PR China
| | - Hikmat A Al-Ahmadie
- Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York
| | - Richard J Wong
- Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York.
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Brea Álvarez B, Tuñón Gómez M. Diseminación perineural en tumores de cabeza y cuello. RADIOLOGIA 2014; 56:400-12. [DOI: 10.1016/j.rx.2014.04.006] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2013] [Revised: 03/20/2014] [Accepted: 04/13/2014] [Indexed: 01/08/2023]
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Müller-Schwefe G, Ahlbeck K, Aldington D, Alon E, Coaccioli S, Coluzzi F, Huygen F, Jaksch W, Kalso E, Kocot-Kępska M, Kress HG, Mangas AC, Ferri CM, Morlion B, Nicolaou A, Hernández CP, Pergolizzi J, Schäfer M, Sichère P. Pain in the cancer patient: different pain characteristics CHANGE pharmacological treatment requirements. Curr Med Res Opin 2014; 30:1895-908. [PMID: 24841174 DOI: 10.1185/03007995.2014.925439] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Twenty years ago, the main barriers to successful cancer pain management were poor assessment by physicians, and patients' reluctance to report pain and take opioids. Those barriers are almost exactly the same today. Cancer pain remains under-treated; in Europe, almost three-quarters of cancer patients experience pain, and almost a quarter of those with moderate to severe pain do not receive any analgesic medication. Yet it has been suggested that pain management could be improved simply by ensuring that every consultation includes the patient's rating of pain, that the physician pays attention to this rating, and a plan is agreed to increase analgesia when it is inadequate. After outlining current concepts of carcinogenesis in some detail, this paper describes different methods of classifying and diagnosing cancer pain and the extent of current under-treatment. Key points are made regarding cancer pain management. Firstly, the pain may be caused by multiple different mechanisms and therapy should reflect those underlying mechanisms - rather than being simply based on pain intensity as recommended by the WHO three-step ladder. Secondly, a multidisciplinary approach is required which combines both pharmacological and non-pharmacological treatment, such as psychotherapy, exercise therapy and electrostimulation. The choice of analgesic agent and its route of administration are considered, along with various interventional procedures and the requirements of palliative care. Special attention is paid to the treatment of breakthrough pain (particularly with fast-acting fentanyl formulations, which have pharmacokinetic profiles that closely match those of breakthrough pain episodes) and chemotherapy-induced neuropathic pain, which affects around one third of patients who receive chemotherapy. Finally, the point is made that medical education should place a greater emphasis on pain therapy, both at undergraduate and postgraduate level.
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Paes FM, Singer AD, Checkver AN, Palmquist RA, De La Vega G, Sidani C. Perineural spread in head and neck malignancies: clinical significance and evaluation with 18F-FDG PET/CT. Radiographics 2014; 33:1717-36. [PMID: 24108559 DOI: 10.1148/rg.336135501] [Citation(s) in RCA: 79] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Certain tumors of the head and neck use peripheral nerves as a direct conduit for tumor growth away from the primary site by a process known as perineural spread. Perineural spread is associated with decreased survival and a higher risk of local recurrence and metastasis. Radiologists play an important role in the assessment and management of head and neck cancer, and positron emission tomography/computed tomography (PET/CT) with 2-[fluorine 18]fluoro-2-deoxy-d-glucose (FDG) is part of the work-up and follow-up of many affected patients. Awareness of abnormal FDG uptake patterns within the head and neck is fundamental for diagnosing perineural spread. The cranial nerves most commonly affected by perineural spread are the trigeminal and facial nerves. Risk of perineural spread increases with a midface location of the tumor, male gender, increasing tumor size, recurrence after treatment, and poor histologic differentiation. Focal or linear increased FDG uptake along the V2 division of the trigeminal nerve or along the medial surface of the mandible, or asymmetric activity in the masticator space, foramen ovale, or Meckel cave should raise suspicion for perineural spread. If FDG PET/CT findings suggest perineural spread, the radiologist should look at available results of other imaging studies, especially magnetic resonance imaging, to confirm the diagnosis. Knowledge of common FDG PET/CT patterns of neoplastic involvement along the cranial nerves and potential diagnostic pitfalls is of the utmost importance for adequate staging and treatment planning.
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Affiliation(s)
- Fabio M Paes
- Department of Radiology, Miller School of Medicine, University of Miami, Jackson Memorial Hospital, West Wing-279, 1611 NW 12th Ave, Miami, FL 33136
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Lv CY, Zhou T, Chen W, Yin XD, Yao JH, Zhang YF. Preliminary study correlating CX3CL1/CX3CR1 expression with gastric carcinoma and gastric carcinoma perineural invasion. World J Gastroenterol 2014; 20:4428-4432. [PMID: 24764683 PMCID: PMC3989981 DOI: 10.3748/wjg.v20.i15.4428] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2013] [Accepted: 03/05/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To study the relationship between the CX3CL1 chemokine, its receptor CX3CR1, and gastric carcinoma/gastric carcinoma perineural invasion (PNI).
METHODS: Thirty cases of gastric carcinoma were surgically resected (radical resection or palliative resection) between February 2012 and July 2012. Tumour and tumour-adjacent tissues were evaluated for the presence of CX3CL1 (ELISA) and CX3CR1 (immunohistochemistry and Western blotting) in an effort to analyse the relationship between CX3CL1/CX3CR1 and gastric carcinoma/gastric carcinoma PNI.
RESULTS: Of these 30 cases, 14 were PNI-positive (46.7%). No significant differences in CX3CL and CX3CR1 expression in tumour-adjacent tissues were found between the PNI positive and negative groups. Expression levels of CX3CL and CX3CR1 in tumour tissues were significantly higher than those in adjacent tissues (P < 0.01), and were significantly higher in tumour tissues from the PNI-positive group compared to the PNI-negative group (P < 0.01).
CONCLUSION: CX3CL1/CX3CR1 expression may be associated with the occurrence and development of gastric carcinoma as well as gastric carcinoma PNI.
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Gorin MA, Chalfin HJ, Epstein JI, Feng Z, Partin AW, Trock BJ. Predicting the risk of non-organ-confined prostate cancer when perineural invasion is found on biopsy. Urology 2014; 83:1117-21. [PMID: 24655556 DOI: 10.1016/j.urology.2013.12.042] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2013] [Revised: 12/10/2013] [Accepted: 12/24/2013] [Indexed: 10/25/2022]
Abstract
OBJECTIVE To more precisely define the risk of non-organ-confined (non-OC) prostate cancer among men with perineural invasion (PNI) identified on prostate biopsy. MATERIALS AND METHODS The Johns Hopkins radical prostatectomy database was queried for men with PNI reported on prostate biopsy. Patients with and without non-OC disease were compared for differences in preoperative clinical and pathologic characteristics, including three biopsy-based measures of tumor volume (number of cores with cancer, percentage of cores with cancer, and maximum percent core involvement with cancer). After evaluating the different preoperative variables in univariate analyses, a multivariable logistic regression model was generated, and bootstrap estimates of the risk of non-OC disease were calculated. RESULTS In total, 556 patients with PNI were analyzed, 279 (50.2%) of whom were found to have non-OC prostate cancer. In univariate analyses, preoperative prostate-specific antigen, clinical T stage, biopsy Gleason sum, and the three biopsy-based measures of tumor volume were significantly associated with non-OC disease. Of the three measures of tumor volume, the best fit to the data and highest degree of model discrimination were obtained using maximum percent core involvement with cancer. Incorporating this variable, preoperative prostate-specific antigen, clinical T stage, and biopsy Gleason sum into a multivariable model, the estimated risk of non-OC disease was found to range from 13.8% to 94.4% (bootstrap corrected c-index = 0.735). CONCLUSION Men with PNI on prostate biopsy are at a wide range of risk for non-OC disease. Preoperative estimation of this risk is improved by considering readily available biopsy estimates of tumor volume.
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Affiliation(s)
- Michael A Gorin
- The James Buchanan Brady Urological Institute, and Department of Urology, The Johns Hopkins School of Medicine, Baltimore, MD.
| | - Heather J Chalfin
- The James Buchanan Brady Urological Institute, and Department of Urology, The Johns Hopkins School of Medicine, Baltimore, MD
| | - Jonathan I Epstein
- Department of Pathology, The Johns Hopkins School of Medicine, Baltimore, MD
| | - Zhaoyong Feng
- The James Buchanan Brady Urological Institute, and Department of Urology, The Johns Hopkins School of Medicine, Baltimore, MD
| | - Alan W Partin
- The James Buchanan Brady Urological Institute, and Department of Urology, The Johns Hopkins School of Medicine, Baltimore, MD
| | - Bruce J Trock
- The James Buchanan Brady Urological Institute, and Department of Urology, The Johns Hopkins School of Medicine, Baltimore, MD
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SHEN ZHIYUAN, LI TIANYI, CHEN DA, JIA SEN, YANG XIANGMING, LIANG LIANG, CHAI JUAN, CHENG XIAOBING, YANG XINJIE, SUN MOYI. The CCL5/CCR5 axis contributes to the perineural invasion of human salivary adenoid cystic carcinoma. Oncol Rep 2013; 31:800-6. [DOI: 10.3892/or.2013.2920] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2013] [Accepted: 10/14/2013] [Indexed: 11/05/2022] Open
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Zhu J, Zhang Y, Xu N, Wang L, Xiang X, Zhu X. The preparation of PLL–GRGDS modified PTSG copolymer scaffolds and their effects on manufacturing artificial salivary gland. JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION 2013; 24:1721-39. [DOI: 10.1080/09205063.2013.797726] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Affiliation(s)
- Jie Zhu
- a School of Pharmaceutical Engineering & Life Science , Changzhou University , Changzhou , 213164 , China
| | - Yueming Zhang
- a School of Pharmaceutical Engineering & Life Science , Changzhou University , Changzhou , 213164 , China
| | - Nanwei Xu
- c Department of Orthopaedics , Changzhou No. 2 People’s Hospital , Changzhou , 213003 , China
| | - Liqun Wang
- a School of Pharmaceutical Engineering & Life Science , Changzhou University , Changzhou , 213164 , China
| | - Xu Xiang
- b State Key Lab of Chemical Resource Engineering , Beijing University of Chemical Technology , Beijing , 100029 , China
| | - Xiaolin Zhu
- a School of Pharmaceutical Engineering & Life Science , Changzhou University , Changzhou , 213164 , China
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Singh N, Eskander A, Huang SH, Curtin H, Bartlett E, Vescan A, Kraus D, O'Sullivan B, Gentili F, Gullane P, Yu E. Imaging and resectability issues of sinonasal tumors. Expert Rev Anticancer Ther 2013; 13:297-312. [PMID: 23477517 DOI: 10.1586/era.13.5] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Sinonasal tumors can invade into the critical structures of the anterior and central skull base. Although the determination of precise tumor histology is difficult with imaging, radiology is important in helping differentiate malignant from benign disease. Imaging helps to map the anatomical extent of intracranial and intraorbital tumor, which has important implications for staging, treatment and prognosis. Imaging also helps to facilitate and plan for craniofacial or endoscopic surgical approaches and radiation planning. This paper will review the locoregional invasion patterns for sinonasal tumors, with emphasis on their imaging features. The authors will discuss the implications for staging, resection potential, choice and details of radiotherapy with or without chemotherapy and prognosis. The imaging assessment of structures and compartments that are critical to the skull base team are highlighted: orbit, cavernous sinus, anterior cranial fossa dura/intracranial tumor, lateral frontal sinus, vascular tumor encasement, perineural tumor spread and tumor effect on the surrounding bony structures.
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Affiliation(s)
- Navneet Singh
- Department of Medical Imaging, Faculty of Medicine, University of Toronto, Toronto, ON, Canada
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