Clinicopathological characteristics and perineural invasion in adenoid
               cystic carcinoma: a systematic review

Dantas, Afonso Nóbrega; Morais, Everton Freitas de; Macedo, Rômulo Augusto de Paiva; Tinôco, João Maria de Lima; Morais, Maria de Lourdes Silva de Arruda

doi:10.1016/j.bjorl.2014.07.016

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Brazilian Journal of Otorhinolaryngology

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Review Article • Braz. j. otorhinolaryngol. 81 (3) • May-Jun 2015 • https://doi.org/10.1016/j.bjorl.2014.07.016 copy

Clinicopathological characteristics and perineural invasion in adenoid cystic carcinoma: a systematic review^☆ ☆ Please cite this article as: Dantas AN, de Morais EF, Macedo RA, Tinôco JM, Morais ML. Clinicopathological characteristics and perineural invasion in adenoid cystic carcinoma: a systematic review. Braz J Otorhinolaryngol. 2015;81:329-35. ^☆☆ ☆☆ Institution: Universidade Potiguar (UnP), Natal, RN, Brazil.

Authorship SCIMAGO INSTITUTIONS RANKINGS

INTRODUCTION:

Adenoid cystic carcinoma is the most frequent malignant tumor of the submandibular gland and the minor salivary glands. It is a malignant neoplasm that, despite its slow growth, shows an unfavorable prognosis.

OBJECTIVES:

The aim of this study was to perform a systematic review of the literature on Adenoid cystic carcinoma in the head and neck region and its clinicopathological characteristics, with emphasis on the perineural invasion capacity of the tumor.

METHODS:

A systematic search of articles published between January 2000 and January 2014 was performed in the PubMed/MEDLINE, SciELO, Science Direct, and Scopus databases.

RESULTS:

Nine articles were selected for this systematic review. These demonstrated that the female gender was more often affected and that malignant tumors showed a high rate of distant metastasis, recurrence, and a low survival rate. The presence of perineural invasion ranged from 29.4% to 62.5% and was associated with local tumor recurrence.

CONCLUSION:

Adenoid cystic carcinoma is commonly characterized by the presence of pain, high rate of recurrence, metastasis, and a low survival rate. Reporting studies with patient follow-up is of utmost importance for a better clinical-pathological understanding and to improve the prognosis of this pathology.

Salivary gland neoplasms; Salivary glands; Mouth neoplasms

Study	Number of patients/gender/age	Location of primary tumor	Metastasis	Treatment	Disease recurrence
DeAngelis et al. (Australia, 2011)³	24 (7 M/17 F), mean age of 58 years (range 30–81 years).	The palate was the most often affected site, representing 37.5% of cases.	4.1% had metastases to the cervical lymph nodes and 4.1%, to the cervical spine.	Surgery was performed in 91.6% patients; 87.5% of cases were associated with radiotherapy. Neck dissection was performed in 20.8% of cases.	25% of the patients had recurrence.
Chen AM et al. (USA, 2006)⁷	140 (81 M/59 F), mean age of 57 years (range 11–91 years).	Parotid (14%); submandibular (18%); sublingual (7%); lacrimal gland (2%); minor salivary glands (24%); oropharynx (9%); hypopharynx (4%); paranasal sinuses (20%); trachea (3%).	25% of patients had distant metastases.	All patients were treated with definitive surgery.	16.4% had recurrence.
Min et al. (China, 2012)⁹	616 (302 M/314 F), mean age of 51.6 years (range 11–89 years).	Parotid gland (11%); submandibular gland (13%); sublingual gland (7.5%); hard/soft palate (26.9%); maxillary sinus (9.7%); tongue ventral surface (2.8%); tongue dorsal surface (8.4%); mouth floor (9.6%); oral mucosa (5%); others (6%).	10.06% of cases had metastases to cervical lymph nodes.	Surgical treatment followed by postoperative radiotherapy was the main option.	Not reported.
Luksi et al. (Croatia, 2013)¹⁰	26 (12 M/14 F), mean age of 58 (range 34–88) years.	Palate (62%); mouth floor (15%); alveolar mucosa (12%); upper lip (8%); jugal mucosa (4%).	46.1% had distant metastases.	Surgical treatment followed by postoperative radiotherapy was the main option.	26.9% had recurrence.
Tincani et al. (Brazil, 2006)¹¹	21 (7 M/14 F), aged 26–72 years.	Parotid (19%); submandibular gland (33.3%); palate (47.6%).	33.3% had regional metastases and 22.2% had distant metastasis.	Surgery was the main treatment with adjuvant radiation therapy in many cases, whereas resection of the structure was necessary in other cases.	38.09% had recurrence.
Bianchi et al. (Italy, 2008)¹²	67 (28 M/39 F), mean age of 54.5 years (range 28–84 years).	Palate (71.6%); lips (3%); alveolar mucosa (1.5); jugal mucosa (4.5%); retromolar region (4.5%); tongue (4.5%); mouth floor (9%); others (1.5%).	29.8% of patients had distant metastases.	All patients were treated with surgery as the primary modality. Dissection was performed in 9% of patients, and over half (59.7%) were treated with adjuvant radiation therapy.	29.8% of patients had recurrence.
Perez et al. (Brazil, 2005)¹³	129 (71 M/58 F), mean age of 51.5 years (range 10–96 years).	Palate (22.5%); tongue (7.7%); jugal mucosa (3.9%); mouth floor (3.9%); upper lip (3.1%); lower lip (0.8%); parotid (19.4%); submandibular (15.5%); sublingual (2.3%); others (20.9%).	10.07% had regional metastases and 8.5% had distant metastasis.	Patients were treated with local resection associated with postoperative radiotherapy (42.7%), local resection alone (30.2%), or radiotherapy alone (10.1%). Other therapeutic modalities included radiotherapy and chemotherapy (3.9%), local resection and chemotherapy (2.3%), and chemotherapy alone (1.5%). 9.3% of patients received only supportive care.	55% had local recurrence.
Khan et al. (USA, 2001)¹⁴	68 (3 0 M/38 F), mean age at diagnosis of 52 years.	The most affected sites were the oropharynx (23.5%), parotid (22.05%), submandibular gland (16.17%).	10.2% had pulmonary metastasis and 5.8% had lymph node metastasis.	The primary treatment was surgery. 8.8% of patients underwent radiation, 7.3% of patients were poor surgical candidates due to comorbidities, and were treated with curative intent, while 1.4% of patients were treated with palliative care.	42.6% had recurrence.
Sung et al. (Korea, 2003)¹⁵	94 (44 M/50 F), age of 44.5 years (range 20–78 years).	The most affected sites were the minor salivary glands (69.1%) and the major salivary glands (30.8%).	26.5% of patients had distant metastases and 3.1% had regional metastasis.	In cases of patients with distant metastases, 10.6% were treated with surgery, 8.5% with radiotherapy, and 29.7% with both. In patients without distant metastasis, 6.3% were treated with surgery, 7.4% with radiotherapy, and 37.2% with both.	18.08% had recurrence.

Study	Size of primary tumor	Histopathological pattern	Perineural invasion	Factors related to perineural invasion
DeAngelis et al. (Australia, 2011)³	Not mentioned.	Solid (37.5%); tubular or cribriform (54,1%); nonspecific pattern (8.3%).	62.5% of patients had perineural invasion.	The presence of perineural invasion can result in a high rate of recurrence.
Chen et al. (USA, 2006)⁷	Not mentioned.	Not mentioned.	58.5% of patients had perineural invasion.	Local recurrence was more frequent in patients with perineural invasion.
Min et al. (China, 2012)⁹	75.3% of the patients had primary tumor <3 cm and 24.6% had tumor >3 cm	Solid (38.63%); tubular or cribriform (61.36%).	52.2% of patients had perineural invasion.	The presence of perineural invasion can result in a high rate of recurrence.
Luksi et al. (Croatia, 2013)¹⁰	Not mentioned.	Not mentioned.	50% of patients had perineural invasion.	There was no significant association between perineural invasion and the primary tumor size or presence of distant metastases, but there was an association with the local tumor extent.
Tincani et al. (Brazil, 2006)¹¹	Not mentioned.	Cribriform (38.08%); tubular (38,08%); solid (23.8%).	42.8% of patients had perineural invasion.	The presence of perineural invasion is closely associated with local tumor recurrence.
Bianchi et al. (Italy, 2008)¹²	Tumor size varied between 1 cm and 9 cm.	Solid (46.2%); cribriform (46.2%); tubular (14.9%).	58.2% of patients had perineural invasion.	The presence of perineural invasion was not associated with the presence of metastasis or the survival rate of the study patients.
Perez et al. (Brazil, 2005)¹³	Minor gland tumors had an average size of 4.1 cm, sublingual of 3.8 cm, and parotid of 3.6 cm.	Cribriform (54.2%); tubular (25.2%); solid (20.6%).	44.9% of patients had perineural invasion.	The presence of perineural invasion was not associated with a negative prognosis.
Khan et al. (USA, 2001)¹⁴	Not mentioned.	51.4% of patients had predominantly solid tumor.	29.4% of patients had perineural invasion.	Sinonasal tumors are more likely to show perineural invasion as well as tumors of minor salivary glands. The presence of positive margin was also associated with perineural invasion.
Sung et al. (Korea, 2003)¹⁵	Not mentioned.	Cribriform (32.9%); tubular (20,2%); solid (11.7%).	30.8% of patients had perineural invasion.	Perineural invasion was not associated with the presence of distant metastases.

Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Sede da Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico Facial, Av. Indianópolia, 1287, 04063-002 São Paulo/SP Brasil, Tel.: (0xx11) 5053-7500, Fax: (0xx11) 5053-7512 - São Paulo - SP - Brazil
E-mail: revista@aborlccf.org.br

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[1] * Corresponding author. E-mail: joao-tinoco@hotmail.com (J.M.d.L. Tinoco).