Role of perineural invasion as a prognostic factor in laryngeal cancer

Abstract

Abstract. The diffusion of laryngeal cancer cells in the perineural space is a parameter associated with a negative prognosis, high loco-regional recurrence and low disease-free survival rates. The spread of tumor cells on the perineural sheath highlights the histopathological and clinically aggressive behavior of this type of tumor, which may extend proximally or distally in the nerve for >10 cm. Therefore, the surgical resection margin is generally insufficient to treat patients with laryngeal cancer presenting with perineural invasion (PNI) with surgery alone. In PNI, the minor laryngeal nerves are frequently involved, rather than the superior and inferior laryngeal nerves. The aim of the present study was: i) To evaluate the prognostic importance of PNI; ii) to correlate the rate of infiltration with factors associated with the tumor, including histotype, site and tumor-node-metastasis stage, and with the type of surgery (total or partial laryngectomy); and iii) to evaluate the rate of disease-free survival according to the outcome of combined surgery and radiotherapy (RT) treatment, by means of retrospective analysis. The results of the present study highlighted the importance of performing a closer clinical and instrumental follow-up in patients with laryngeal cancer whose histopathological examination is positive for PNI. In such cases, it is important to complement the surgical therapeutic treatment with adjuvant RT. IntroductionPerineural invasion (PNI), also known as neurotropic carcinomatous spread, is a process predominantly characterized by neoplastic invasion of the nerves. PNI may also occur in the absence of lymphatic or vascular invasion (1-5).In PNI, the propagation of neoplastic cells to the primitive site of the tumor does not occur via lymphatic dissemination, but through molecular mediators that guide these cells during the invasion of the nerve sheath (6). The definition of PNI was first proposed in a study by Batsakis (3), according to which, PNI was 'a tumor cell invasion in, around and through the nerve'. Following multiple modifications, PNI is currently defined as 'the presence of tumor cells in the 3 layers of the nerve sheath' or 'in close proximity to nerve, involving at least 33% of its entire circumference'; below this cut-off, focal abutment rather than PNI should be considered (1,6).The incidence of PNI has been reported to vary from 6 to 50% for head and neck cancer, and <80% for squamocellular carcinoma. PNI is an independent negative prognostic factor associated with a lesser loco-regional control of the disease and poor survival in patients with laryngeal cancer (1,2,(6)(7)(8)(9)(10)(11)(12)(13)(14). The aim of the present study was: i) To evaluate the prognostic importance and incidence of PNI; ii) to correlate the infiltration rate with factors associated to the tumor, including histotype, site and tumor-node-metastasis stage (TNM), and with the type of surgery (total or partial laryngectomy); iii) to evaluate the disease-free survival rate according to the outcome of com...

Open Partial Horizontal Laryngectomies for T3–T4 Laryngeal Cancer: Prognostic Impact of Anterior vs. Posterior Laryngeal Compartmentalization

“…The presence of PNI was confirmed to have a significant negative impact in both uni- and multivariate analyses. This finding was previously reported by other authors [34,35,36,37]. In particular, Chirila et al analyzed a cohort of 256 patients treated for laryngeal and hypopharyngeal cancers and reported the presence of PNI in 35.6% of cases—which corresponds well with the rate observed herein—with a significant impact of minor nerve PNI on DSS and RFS [34].…”

Overexpression of chromatin assembly factor-1/p60 predicts biological behaviour of laryngeal carcinomas

“…), for LC there are no specific and sensitive markers that can be used for early diagnosis and follow-up, beyond the available prognostic parameters 4 5 . Cell proliferative activity has been extensively investigated in head and neck tumours, including LC, as useful diagnostic and prognostic marker; however, its specific role has yet to be definitively established.…”

Defining the Prevalence and Prognostic Value of Perineural Invasion and Angiolymphatic Invasion in Human Papillomavirus–Positive Oropharyngeal Carcinoma

“…[9][10][11][12] Perineural invasion influences recurrence, distant metastases, and survival in several head and neck sites, including the oropharynx, oral cavity, hypopharynx, and larynx. [13][14][15][16][17] Angiolymphatic invasion has received less attention than PNI, likely because it is difficult to recognize and has subsequently been omitted from some histologic grading systems. 9,18 Studies [18][19][20][21] have found an association between ALI and worse treatment outcomes; however, overall the literature is mixed, and additional studies to elucidate the significance of this association are indicated.…”