Prognostic factors in head and neck adenoid cystic carcinoma

doi:10.1016/j.oraloncology.2005.06.024

Oral Oncology

Volume 42, Issue 2, February 2006, Pages 139-146

https://doi.org/10.1016/j.oraloncology.2005.06.024 Get rights and content

Summary

The aim of this study was to analyse the clinical, histological and immunohistochemical prognostic factors of a large series of adenoid cystic carcinoma, using univariate and multivariate survival analyses. All cases of head and neck ACC (n = 129) treated in a single institution in Brazil, between 1955 and 1997, were selected for the study. Univariate survival analysis revealed that age older than 45 years (p = 0.04), period of complaints inferior to 18 months (p = 0.007), presence of paresthesia (p = 0.04), T stage (p = 0.01), N stage (p = 0.04), M stage (p < 0.001), clinical stage (p = 0.003), solid histological type (p < 0.001), presence of residual tumor (p < 0.001) and expression of p53 (p = 0.08) correlated with a poor prognosis. In the multivariate survival analyses, clinical stage, solid histological subtype and increased expression of p53 were independent significant prognostic factors. According to our findings, clinical stage, solid growth pattern and expression of p53 were the most important prognostic factors in patients with ACC.

Introduction

Adenoid cystic carcinomas (ACC) are uncommon head and neck tumors, corresponding to 4–10% and 7.5% of all epithelial tumors and malignancies of the salivary glands respectively.1, 2 ACC typically presents an indolent and slow growth associated to frequent late distant metastases, which are together with local recurrences, the reasons for the low long-term survival rate.2, 3, 4

Standard treatment has not yet been established, although many series of ACC have been described. Some authors have reported an increase local control of the disease with combined surgical and radiotherapy treatments.⁵ However, other studies were not able to demonstrate a significant effect for postoperative radiotherapy.4, 6 Several studies showed that advanced clinical stage and solid histological subtype are relevant prognostic factors associated with survival of the patients.4, 6, 7 Some immunohistochemical markers, such as p53, bcl-2 and cell proliferation markers have been associated to survival of patients with ACC.8, 9, 10, 11 Nevertheless few studies have associated survival with the clinical, histological and immunohistochemical features in a large series of head and neck ACC. Therefore, the aim of this study was to analyze the clinical, histological and immunohistochemical prognostic factors of 129 patients with ACC treated in a single institution.

Section snippets

Patients and methods

Between the years of 1955 and 1997, all patients diagnosed as having ACC, from the Department of Head and Neck Surgery and Otorhinolaryngology, Hospital do Cancer A. C. Camargo, Sao Paulo, Brazil, were included in this study. This study was performed with the approval of the Human Research Ethics Committee of this Hospital. Clinical, epidemiological, treatment and follow-up data were obtained from the medical records. TNM restaging was established according to Sobin and Wittekind.¹² All cases

Clinical

Of the 129 patients with ACC included in this study, 71 were male (55%) and 58 female (45%), giving a male-female ratio of 1.22:1. The mean age of the patients was 51.5 years (range 10–96 years), being the women older (mean 53.4 years) than men (mean 50.2 years). The mean time of complaints was 39.4 months (range 1–360 months), and the most common signs and symptoms were the presence of a nodule (92.1%), pain (59.8%), paresthesia (12.6%) and nasal congestion (11.8%). Most tumors involved the

Discussion

Adenoid cystic carcinoma most commonly occurs during the fifth and sixth decades of life,3, 4, 7 as in our series. In children and adolescents, ACC is extremely rare.¹³ We found a slight male predilection, although other studies showed a female or no gender predilection.2, 4, 6, 7 ACC occurs mainly in the intraoral salivary glands, particularly in the palate, and parotid, followed by submandibular, extraoral, and sublingual salivary glands,7, 14 similar to our findings. However, other sites in

Acknowledgements

This work was supported by The State of Sao Paulo Research Foundation (FAPESP) and National Council for Scientific and Technological Development (CNPq), Brazil.

References (27)

H. Kokemueller et al.
Adenoid cystic carcinoma of the head and neck—a 20 years experience
Int J Oral Maxillofac Surg
(2004)
C.M.E. Avery et al.
Combined treatment of adenoid cystic carcinoma of the salivary glands
Int J Oral Maxillofac Surg
(2000)
Q.R. Zhu et al.
p53 oncoprotein accumulation in adenoid cystic carcinoma of parotid and palatine salivary glands
Pathology
(1997)
T. Kiyoshima et al.
Expression of p53 supressor gene in adenoid cystic carcinoma and mucoepidermoid carcinomas of the salivary glands
Oral Oncol
(2001)
D.E. da Cruz Perez et al.
Salivary glands tumors in children and adolescents: a clinicopathologic and immunohistochemical study of fifty-three cases
Int J Pediatric Otorhinolaryngol
(2004)
R.H. Spiro et al.
Stage means more than grade in adenoid cystic carcinoma
Am J Surg
(1992)
A.D. Rapidis et al.
Adenoid cystic carcinoma of the head and neck. Clinicopathological analysis of 23 patients and review of the literature
Oral Oncol
(2005)
R.H. Spiro et al.
Adenoid cystic carcinoma of salivary origin. A clinicopathologic study of 242 cases
Am J Surg
(1974)
L. Miglianico et al.
Cervico-facial adenoid cystic carcinoma: study of 102 cases. Influence of radiation therapy
Int J Radiat Oncol Biol Phys
(1987)
A.S. Garden et al.
The influence of positive margins and nerve invasion in adenoid cystic carcinoma of the head and neck treated with surgery and radiation
Int J Radiat Oncol Biol Phys
(1995)

E.P. Prokopakis et al.

Risk factors for local recurrence of adenoid cystic carcinoma: the role of postoperative radiation therapy

Am J Otolaryngol

(1999)

Ellis GL, Auclair P. Tumors of the salivary glands: atlas of tumor pathology. Washington, DC: Armed Forces Institute of...

J.E. van der Wal et al.

Distant metastases of adenoid cystic carcinoma of the salivary glands and the value of diagnostic examinations during follow-up

Head Neck

(2002)

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Adenoid cystic carcinoma (AdCC) is a rare and relatively heterogenous salivary gland malignancy, for which there is debate regarding grading, and clinical prognostic factors, including the role of adjuvant radiotherapy.
Surveillance, Epidemiology, and End Results (SEER) data were reviewed for AdCC cases from 2000 to 2018.
A total of 1978 patients with AdCC were identified. Most patients were between 50 and 59 years of age (21.4 %), female (59.9 %), and Caucasian (76.8 %). Most tumors were localized at presentation (44.3 %), and moderately differentiated (or grade II) (43.7 %). Overall and DSS 5-year survival rates were 70.7 % (95 % CI, 69.9–78.8), and 78.6 % (95 % CI, 77.6–79.6). The best overall 5-year survival rate was observed for those treated with surgery plus radiation, 76.8 % (95 % CI, 75.5–78.1). Multivariate analysis revealed male sex, age > 65 (H.R. 2.659 (95 % CI,2.291–3.098), p < .001), grade III/IV (H.R.5.172 (95 % CI, 3.418–7.824), p < .001), nodal metastasis, distant metastasis (H.R. 2.400 (95 % CI, 2.178–2.645), p < .001), chemotherapy only, and combination therapy as negative prognostic factors, and receiving surgery plus radiation therapy (H.R.0.586 (95 % CI, 0.505–0.679), p < .001) as a positive prognostic factor. When limited just to the lungs, had much better survival than those patients with distant metastases to other sites such as the bones and liver (p < .001).
This SEER study identifies grade, particularly III and IV, to be the strongest single predictor of worse survival. Patients did best when treated with surgery and postoperative radiotherapy. These results can inform future management of patients with this challenging cancer type.
Evaluation of cell proliferation marker CDC-7 in salivary adenoid cystic carcinoma
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Adenoid cystic carcinoma (AdCC) is considered one of the most common destructive types of malignant salivary gland tumor that have high affinity to perineural invasion (PNI). This study was conducted to access different histological features of AdCC, and assessment of the immunohistochemical expression of CDC-7.
Thirty formalin-fixed paraffin incorporated tissue blocks of AdCC were classified according to the WHO histopathological types. The immune-expression of CDC-7 positive area was evaluated according to percentage area as following: Negative = 0 %, Weak = 1–10 %, Moderate = 11–49 %, and Strong = 50–100. The correlations between expression of the marker and different clinico-pathological variables were investigated using Chi-square (χ2) test. The P‐value ≤ 0.05 was considered statistically significant.
The expression of CDC-7 revealed statistical significant difference between the different tumor types (p ≤ 0.05).
The biological behavior of AdCC can be predicated from the expression of CDC-7.
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Malignant tumors of the salivary glands are uncommon pathological entities, representing less than 5% of head and neck neoplasms. The prognosis of patients with malignant tumors of the salivary glands is highly variable and certain clinical factors can significantly influence overall survival.
To analyze the clinicopathologic and sociodemographic characteristics that influence survival in patients with malignant tumors of the salivary glands
This retrospective study analyzed sex, age, race, education level, tumor location, tumor size, lymph node involvement, distant metastasis, margin status, treatment type, marital status, method of health care access and 15-year overall survival in 193 patients with malignant tumors of the salivary glands. The X², log-rank Mantel-Cox, multinomial regression and Cox logistic regression tests were used (SPSS 20.0,p < 0.05).
The most common histological types were adenocarcinoma (32.1%), adenoid cystic carcinoma (31.1%) and mucoepidermoid carcinoma (18.7%). The 15-year overall survival rate was 67.4%, with a mean of 116 ± 6 months. The univariate analysis revealed that male sex (p = 0.026), age > 50 years (p = 0.001), referral origin from the public health system (p = 0.011), T stage (p = 0.007), M stage (p < 0.001), clinical stage (p < 0.001), compromised surgical margins (p = 0.013), and chemotherapy (p < 0.001) were associated with a poor prognosis. Multivariate analyses also showed that age > 50 years was independently associated with a poor prognosis (p = 0.016). The level of education was the only factor more prevalent in older patients (p = 0.011).
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Determine rates of intra-parotid and neck nodal metastasis, identify risk factors for recurrence, and report outcomes in patients with primary high-grade parotid malignancy who undergo total parotidectomy and neck dissection.
Retrospective review of patients undergoing total parotidectomy and neck dissection for high-grade parotid malignancy between 2005 and 2015. The presence and number of parotid lymph nodes, superficial and deep, as well as cervical lymph nodes involved with metastatic disease were assessed. Risk factors associated with metastatic spread to the parotid deep lobe were identified and recurrence rates reported.
75 patients with median follow-up time of 47 months. 35 patients (46.7%) had parotid lymph node metastasis. Seven patients (9.3%) had deep lobe nodal metastasis without metastasis to the superficial lobe nodes. Nine patients (12%) had positive intra-parotid nodes without positive cervical nodes. Cervical nodal disease was identified in 49.3% patients (37/75). Local, parotid-bed recurrence rate was 5.3% (4/75). Regional lymph node recurrence rate was also 5.3% (4/75). Rate of distant metastasis was 30.6% (23/75). The overall disease free survival rate for all patients at 2 and 5 years were 71% and 60% respectively.
Parotid lymph node metastasis occurred at a similar rate to cervical lymph node metastasis (46.7% and 49.3%, respectively). Deep lobe parotid nodal metastasis occurred in nearly a quarter of patients and can occur without superficial parotid nodal metastasis. Rate of recurrence in the parotid bed, which may represent local or regional recurrence, was similar to regional cervical lymph node recurrence. Total parotidectomy and neck dissection should be considered high-grade parotid malignancy regardless of clinical nodal status.
Delayed diagnosis of palatal adenoid cystic carcinoma: Review of diagnostic workup and image features of perineural spread
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Adenoid cystic carcinoma (ACC) is the malignancy most likely to spread perineurally. Delayed diagnosis often leads to undetected perineural spread (PNS). Better understanding of diagnostic processes, clinical and imaging features in ACC may allow earlier diagnoses.
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44 patients met inclusion and exclusion criteria. Symptoms included pain, mass, numbness, and sinonasal congestion. The most common finding on clinical examination was visible or palpable palatal mass. 55% of patients were evaluated by a dentist pre-diagnosis. Most common initial impressions were infection and/or dental disease. PNS was identified in 81.8% of patients, most commonly at pterygopalatine fossa, palatine foramina/canals, Vidian canal, or foramen rotundum. PNS was statistically significantly associated with paresthesia (p = 0.003) but not with tumor size, age, gender, or tobacco history. 44% of patients were diagnosed ≥1 year from initial symptoms, with a mean delay of 18.3 (range < 1–72) months.
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