Salivary Gland Pleomorphic Adenomas Presenting With Extremely Varied Clinical Courses. A Single Institution Case-Control Study†

Abstract

ObjectivePleomorphic adenomas (PAs) with divergent clinical behavior, differing from the vast majority of PAs, were distinguished. “Fast” PAs are characterized by an unexpectedly short medical history and relatively rapid growth. The reference group consisted of “slow” PAs with very stable biology and long-term progression. We divide the PA group as a whole into three subsets: “fast,” “normal,” and “slow” tumors. Our goal is a multifactorial analysis of the “fast” and “slow” PA subgroups.MethodsConsecutive surgeries in a tertiary referral center, the Department of Otolaryngology and Laryngological Surgery, Poznan University of Medical Sciences, Poland, were carried out between 2002 and 2011. Out of 1,154 parotid tumors, 636 (55.1%) were PAs. The data were collected prospectively in collaboration with the Polish National Registry of Benign Salivary Gland Tumors. The main outcome measure was the recurrence rate in “fast” and “slow” PA subgroups. All surgical qualifications and surgeries were performed by two experienced surgeons.ResultsSlow PAs, compared to fast PAs, presented in older patients (53.25 ± 15.29 versus 47.92 ± 13.44 years). Multifactor logistic regression analysis with recurrence (yes/no) as the outcome variable, fast/slow as the predictor variable and age, gender, margin, FN status as covariates showed that fast PAs were significantly predicting recurrence vs. slow PAs (p = 0.035). Fast PAs were increasing the risk of PAs 10-fold vs. slow PAs, exp β = 10.20, CI95 [1.66; 197.87]. The variables impacting relapse were recent accelerated growth of the tumor OR = 3.35 (SE = 0.56), p = 0.030, positive margins OR = 7.18 (SE = 0.57), p < 0.001, incomplete or bare capsule OR = 9.91 (SE = 0.53), p = 0.001 and location III OR = 3.12 (SE = 0.53), p = 0.033. In the multivariate model only positive margin was selected as the best predictor of relapse, OR = 5.01 (SE = 0.60), p = 0.007.ConclusionsThe simple clinical aspect of slow or fast PA progression is of great practical importance and can constitute a surrogate of the final histopathological information that is derived from the surgical specimen. The slow or fast nature of the PA to some extent indicates prognostic features such as recurrence risk. This finding requires correlation with histological and molecular features in further stages of research.

Global DNA Methylation Profiling Reveals Differentially Methylated CpGs between Salivary Gland Pleomorphic Adenomas with Distinct Clinical Course

“…Recent decades have brought a marked increase in the incidence of salivary gland tumors [ 5 , 12 , 20 ]. Among them, pleomorphic adenomas are the most frequent, and as previously observed, their development may vary in the context of tumor growth rate and malignant transformation [ 12 , 21 ].…”

“…Recent decades have brought a marked increase in the incidence of salivary gland tumors [ 5 , 12 , 20 ]. Among them, pleomorphic adenomas are the most frequent, and as previously observed, their development may vary in the context of tumor growth rate and malignant transformation [ 12 , 21 ]. On one hand, at the stage of initial diagnosis, both pathologists as well as clinicians are not able to assign the tumor to the fast-growing or slow-growing cohort.…”

“…Such tumors grow faster, and patients may observe the enlarging thickening in the neck/lower jaw area even within a few months. The observed differences were recently described by Piwowarczyk et al, who distinguished three groups of PAs: (I) fast-growing, (II) normal/stable, and (III) slow-growing based on the clinical and radiological data of 636 PAs patients [ 12 ]. The reason for such diversity in the clinical behavior is so far unknown.…”

“…At the stage of PA diagnosis, neither the pathologist (based on fine needle aspiration biopsy (FNA)), nor the clinician (based on patients’ history, clinical examination, and imaging) is able to categorize the tumor, i.e., to predict its fast- or slow-growing nature. Although the level of malignant transformation rate of PAs is not high, they may recur, predominantly within the fast-growing group, which results in the necessity of additional surgery and inconvenience for the patient [ 12 ]. The relapse occurrence depends mainly on the surgeon’s skills; however, adverse PA findings, such as high tumor growth rate, multifocal character, and lack of encapsulation, and its ability for malignant transformation depend on the tumor biology.…”

Expression of p16Ink4aprotein in pleomorphic adenoma and carcinoma ex pleomorphic adenoma proves diversity of tumour biology and predicts clinical course

“…7 In this paper, we present a new insight into a single histological unit: PA. Our 20-year experience of 1500 PAs and extensive observation of their individually variable disease courses has prompted us to distinguish two clinically divergent subsets: 'fast' and 'slow' tumours. 8 While 'fast' PAs are characterised by a short medical history and rapid growth, 'slow' PAs demonstrate very stable biology and long-term growth. Progression, recurrence and malignant transformation are well-established PA behaviours, but the extremely fast growth of this benign tumour has always been a cause of concern for clinicians.…”