Salivary gland cancer: ESMO–European Reference Network on Rare Adult Solid Cancers (EURACAN) Clinical Practice Guideline for diagnosis, treatment and follow-up
2022; Elsevier BV; Volume: 7; Issue: 6 Linguagem: Inglês
10.1016/j.esmoop.2022.100602
ISSN2059-7029
AutoresC. van Herpen, Vincent Vander Poorten, Alena Skálová, Chris H.J. Terhaard, Roberto Maroldi, A. van Engen, B. Baujat, Laura D. Locati, Alexandra Jensen, Ludi E. Smeele, José A. Hardillo, Valérie Costes Martineau, Annalisa Trama, E. Kinloch, C. Even, Jean-Pascal Machiels,
Tópico(s)Tumors and Oncological Cases
Resumo•This ESMO–EURACAN Clinical Practice Guideline provides key recommendations for managing salivary gland cancer.•The guideline covers clinical and pathological diagnosis, staging and risk assessment, treatment and follow-up.•Treatment algorithms for parotid, submandibular, sublingual and minor salivary gland cancer are provided.•The author group encompasses a multidisciplinary group of experts from different institutions and countries in Europe.•Recommendations are based on available scientific data and the authors' collective expert opinion. Major salivary gland cancers (SGCs) comprise 5% of head and neck cancers in Europe. The worldwide crude and age-adjusted incidence rates are 0.69 and 0.57 cases per 100 000 people per year, respectively, with 53 583 new patients in 2020. In Europe, crude and age-adjusted incidence rates are 1.3 and 0.67 cases per 100 000 people per year, respectively, with 9917 new patients in 2020.1Ferlay J. Ervik M. Lam F. et al.Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer.https://gco.iarc.fr/todayDate accessed: February 14, 2022Google Scholar Data for minor SGCs are limited, but the RARECARENet project estimated the crude incidence of minor salivary gland-type cancers of the head and neck to be 0.4 cases per 100 000 people in the 2000-2007 diagnosis period; minor SGCs have a slight predominance in males and incidence is highest in the elderly (>65 years).2RARECARENet. Information Network on Rare Cancers.http://rarecarenet.istitutotumori.mi.it/Date accessed: February 14, 2022Google Scholar History of head and neck cancer and cervicofacial radiotherapy (RT) have both been associated with an increased risk of major SGC [odds ratio (OR) 17.06, 95% confidence interval (CI) 4.34-67.05 and OR 31.74, 95% CI 2.48-405.25, respectively].3Radoi L. Barul C. Menvielle G. et al.Risk factors for salivary gland cancers in France: results from a case-control study, the ICARE study.Oral Oncol. 2018; 80: 56-63Crossref PubMed Scopus (15) Google Scholar,4Lin H.H. Limesand K.H. Ann D.K. Current state of knowledge on salivary gland cancers.Crit Rev Oncog. 2018; 23: 139-151Crossref PubMed Scopus (38) Google Scholar Industries such as cereal and other crop production, furniture manufacturing, interurban road transport and industrial cleaning have also been associated with an increased risk of major SGC.3Radoi L. Barul C. Menvielle G. et al.Risk factors for salivary gland cancers in France: results from a case-control study, the ICARE study.Oral Oncol. 2018; 80: 56-63Crossref PubMed Scopus (15) Google Scholar, 4Lin H.H. Limesand K.H. Ann D.K. Current state of knowledge on salivary gland cancers.Crit Rev Oncog. 2018; 23: 139-151Crossref PubMed Scopus (38) Google Scholar, 5Cong X. Air pollution from industrial waste gas emissions is associated with cancer incidences in Shanghai, China.Environ Sci Pollut Res Int. 2018; 25: 13067-13078Crossref PubMed Scopus (48) Google Scholar Smoking only seems to increase the risk of developing major SGCs other than mucoepidermoid carcinoma (MEC) (OR 5.15, 95% CI 2.06-12.87)6Sawabe M. Ito H. Takahara T. et al.Heterogeneous impact of smoking on major salivary gland cancer according to histopathological subtype: a case-control study.Cancer. 2018; 124: 118-124Crossref PubMed Scopus (18) Google Scholar; however, ionising radiation is the only well-established risk factor.7Boukheris H. Curtis R.E. Land C.E. et al.Incidence of carcinoma of the major salivary glands according to the WHO classification, 1992 to 2006: a population-based study in the United States.Cancer Epidemiol Biomarkers Prev. 2009; 18: 2899-2906Crossref PubMed Scopus (201) Google Scholar,8Alvi S. Chudek D. Limaiem F. Cancer, Parotid. Treasure. StatPearls Publishing, Island, FL2020Google Scholar SGCs include >20 distinct histological subtypes. Given their rarity and heterogeneity, population-based epidemiological studies providing incidence rates according to histology are limited. SGC typically occurs in the sixth and seventh decades of life and has a male predominance2RARECARENet. Information Network on Rare Cancers.http://rarecarenet.istitutotumori.mi.it/Date accessed: February 14, 2022Google Scholar; however, age at diagnosis and gender predominance vary by histology. MEC, adenoid cystic carcinoma (AdCC) and acinic cell carcinoma (AcCC) tend to occur at an earlier age than adenocarcinoma and squamous cell carcinoma (SCC). MEC, AdCC and AcCC are more common in females up to ∼50 years of age; however, incidence of AdCC and AcCC is similar for females and males at older ages, whereas MEC has a higher incidence rate among older males.7Boukheris H. Curtis R.E. Land C.E. et al.Incidence of carcinoma of the major salivary glands according to the WHO classification, 1992 to 2006: a population-based study in the United States.Cancer Epidemiol Biomarkers Prev. 2009; 18: 2899-2906Crossref PubMed Scopus (201) Google Scholar The ratio of tumour diagnoses in parotid, submandibular, minor and sublingual subsites is 100:10:10:1, and the proportion of malignant tumours at these sites is 20%, 50%, 50% and 80%, respectively.9Bradley P.J. McGurk M. Incidence of salivary gland neoplasms in a defined UK population.Br J Oral Maxillofac Surg. 2013; 51: 399-403Abstract Full Text Full Text PDF PubMed Scopus (139) Google Scholar SGC incidence has not increased between 1995 and 2007 in Europe10Gatta G. Capocaccia R. Botta L. et al.Burden and centralised treatment in Europe of rare tumours: results of RARECAREnet – a population-based study.Lancet Oncol. 2017; 18: 1022-1039Abstract Full Text Full Text PDF PubMed Scopus (230) Google Scholar or between 1995 and 2010 in the United States.7Boukheris H. Curtis R.E. Land C.E. et al.Incidence of carcinoma of the major salivary glands according to the WHO classification, 1992 to 2006: a population-based study in the United States.Cancer Epidemiol Biomarkers Prev. 2009; 18: 2899-2906Crossref PubMed Scopus (201) Google Scholar The 5-year relative survival rate (estimated as the ratio of observed to expected survival in the general population, matched by age, sex, calendar year and geographical area) for patients with major SGC is 63% (95% CI 62% to 63.7%) in Europe.10Gatta G. Capocaccia R. Botta L. et al.Burden and centralised treatment in Europe of rare tumours: results of RARECAREnet – a population-based study.Lancet Oncol. 2017; 18: 1022-1039Abstract Full Text Full Text PDF PubMed Scopus (230) Google Scholar This decreases with age, from ∼90% (95% CI 91% to 97%) in patients aged 65 years. Five-year relative survival is higher in females (72%, 95% CI 71% to 74%) than in males (55%, 95% CI 54% to 56%). Furthermore, 5-year relative survival differs across European regions, with the highest rate of 74% (95% CI 71% to 78%) reported in Nordic countries (Finland, Iceland, Norway) and the lowest rate of 52% (95% CI 50% to 54%) reported in Eastern European countries (Bulgaria, Czech Republic, Estonia, Latvia, Lithuania, Poland, Slovakia). SGC relative survival has not improved in Europe between 1999 and 2007.2RARECARENet. Information Network on Rare Cancers.http://rarecarenet.istitutotumori.mi.it/Date accessed: February 14, 2022Google Scholar The 5-year relative survival rate for minor salivary gland-type cancers of the head and neck is 67% and is higher in females than in males. Five-year survival rates are highest in children (>90%) and patients aged 65 years. In Europe during the period 1999-2007, 5-year survival remained stable and was highest in Nordic countries (84%) and lowest in Eastern European countries (55%).2RARECARENet. Information Network on Rare Cancers.http://rarecarenet.istitutotumori.mi.it/Date accessed: February 14, 2022Google Scholar SGC should be classified according to the World Health Organization (WHO) Classification of Head and Neck Tumours.11El Naggar A.K. Chan J.K. Grandis J.R. et al.World Health Organization (WHO) Classification of Head and Neck Tumours.4th ed. IARC Press, Lyon, France2017Google Scholar Including both benign and malignant tumours, there are over 30 distinct salivary gland tumour types in the latest WHO classification system (see Supplementary Table S1, available at https://doi.org/10.1016/j.esmoop.2022.100602, for classification of the malignant tumour types). The symptoms of SGC depend on tumour location. Symptoms that should prompt consideration of SGC include pain in the face or mouth, an externally or submucosally growing lump or (facial) nerve paralysis. Cytology or histology is mandatory. Ultrasound-guided salivary gland fine-needle aspiration (FNA) cytology has become the accepted minimally invasive method for evaluating parotid and submandibular gland tumours preoperatively. This can distinguish malignant from benign disease in 90% of cases if examined by a pathologist experienced in salivary gland disease.12Faquin W. Rossi E.D. The Milan System for Reporting Salivary Gland Cytopathology. Springer, New York, NY2018Crossref Scopus (0) Google Scholar The Milan system for reporting salivary gland cytopathology is recommended. It facilitates standardised reporting and links each diagnostic category to a risk of malignancy (ROM); risks were recently confirmed in a large meta-analysis.13Farahani S.J. Baloch Z. Retrospective assessment of the effectiveness of the Milan system for reporting salivary gland cytology: a systematic review and meta-analysis of published literature.Diagn Cytopathol. 2019; 47: 67-87Crossref PubMed Scopus (45) Google Scholar The Milan system facilitates ROM-associated therapeutic approaches, e.g. initial treatment can be intensified when high-grade malignancy is suspected (one study reported 99% diagnostic accuracy14Kim B.Y. Hyeon J. Ryu G. et al.Diagnostic accuracy of fine needle aspiration cytology for high-grade salivary gland tumors.Ann Surg Oncol. 2013; 20: 2380-2387Crossref PubMed Scopus (44) Google Scholar) (see Supplementary Table S2, available at https://doi.org/10.1016/j.esmoop.2022.100602).12Faquin W. Rossi E.D. The Milan System for Reporting Salivary Gland Cytopathology. Springer, New York, NY2018Crossref Scopus (0) Google Scholar If FNA is non-diagnostic or if the clinical situation requires more information on histotype, core needle biopsy, while more demanding and with a slightly increased risk of complications,15Howlett D.C. Triantafyllou A. Evaluation: fine needle aspiration cytology, ultrasound-guided core biopsy and open biopsy techniques.Adv Otorhinolaryngol. 2016; 78: 39-45PubMed Google Scholar has less inadequate sampling (risk ratio 0.85) and a higher diagnostic yield than FNA.16Cho J. Kim J. Lee J.S. et al.Comparison of core needle biopsy and fine-needle aspiration in diagnosis of malignant salivary gland neoplasm: systematic review and meta-analysis.Head Neck. 2020; 42: 3041-3050Crossref PubMed Scopus (15) Google Scholar It is thus an accepted next step in the diagnostic work-up.17Romano E.B. Wagner J.M. Alleman A.M. et al.Fine-needle aspiration with selective use of core needle biopsy of major salivary gland tumors.Laryngoscope. 2017; 127: 2522-2527Crossref PubMed Scopus (23) Google Scholar Open biopsies should be avoided in major salivary gland lesions due to the risk of complicating definitive surgical treatment and the risk of spillage, with the exception of skin ulcerating tumours. For minor salivary gland tumours, an experienced surgeon should take a biopsy of the tumour and surrounding stroma.18Ihrler S. Agaimy A. Guntinas-Lichius O. et al.Why is the histomorphological diagnosis of tumours of minor salivary glands much more difficult?.Histopathology. 2021; 79: 779-790Crossref PubMed Scopus (9) Google Scholar Incisional biopsy is recommended for submucosally extending tumours, and an incisional or forceps biopsy should be taken for ulcerating lesions. Ultrasound, computed tomography (CT), magnetic resonance imaging (MRI) and [18F]2-fluoro-2-deoxy-D-glucose–positron emission tomography (FDG–PET) are the imaging techniques most commonly used to assess lesions in the major salivary glands, with MRI being the preferred modality (see Figure 1). Diagnostic imaging techniques are described in Section 1 of the Supplementary Material, available at https://doi.org/10.1016/j.esmoop.2022.100602. The SGC histological type essentially defines its biological behaviour, which influences prognosis and patterns of recurrence, and thus clinical management. Some SGC types, such as basal cell adenocarcinoma, low-grade MEC, intraductal carcinoma and conventional AcCC, are indolent, with high risk of locoregional recurrence but low rates of nodal involvement and distant metastases.19Seethala R.R. An update on grading of salivary gland carcinomas.Head Neck Pathol. 2009; 3: 69-77Crossref PubMed Scopus (229) Google Scholar Immunohistochemistry (IHC) on the surgical specimen provides supplementary visualisation of cell compartments and cell populations, thus improving SGC taxonomy. The role of molecular diagnostics in SGC is evolving. Many monomorphic SGCs are now known to harbour defining balanced translocations, some of which are readily evaluable on paraffin-embedded materials either by FISH, RT–PCR or next-generation sequencing (NGS).20Skalova A. Stenman G. Simpson R.H.W. et al.The role of molecular testing in the differential diagnosis of salivary gland carcinomas.Am J Surg Pathol. 2018; 42: e11-e27Crossref PubMed Scopus (126) Google Scholar Recently, NGS has provided significant input on the molecular characterisation of SGC subtypes, improving diagnostic differentiation between morphologically similar tumour types and also identifying novel driver pathways that determine tumour biology and which may be amenable to targeted therapy [see European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT) for further details in Supplementary Table S3, available at https://doi.org/10.1016/j.esmoop.2022.100602]. SGC histological subtypes are described in detail in Section 2 of the Supplementary Material, available at https://doi.org/10.1016/j.esmoop.2022.100602. Key molecular alterations in SGC are described in Supplementary Table S4, available at https://doi.org/10.1016/j.esmoop.2022.100602. •Classification should be carried out according to the WHO Classification of Head and Neck Tumours [I, A].•Clinical examination and pathological confirmation are mandatory [IV, A].•FNA should be used for screening; if inadequate, core needle biopsy can be a next step [III, A].•FNA results should be reported according to the Milan classification, including a defined ROM and suggested therapeutic approaches [IV, A].•For minor salivary gland tumours, an experienced surgeon should take a biopsy of the tumour and surrounding stroma. For submucosally extending tumours, an incisional biopsy, and for ulcerating lesions an incisional or forceps biopsy should be taken [IV, A].•When malignancy is suspected, MRI is the preferred imaging modality [IV, A].•Contrast-enhanced CT is mostly limited to patients in whom MRI is contraindicated [IV, B].•Regardless of the imaging technique used, the study should be extended to include the ipsilateral and contralateral neck levels or integrated with ultrasound examination of neck lymph nodes [III, A].•FDG–PET–CT is recommended in high-grade SGC for the detection of distant metastases [III, A].•IHC and molecular testing should be used as supplementary tools when appropriate [IV, A]. Confirmation of androgen receptor and human epidermal growth factor receptor 2 (HER2) status is mandatory in salivary duct carcinoma and adenocarcinoma not otherwise specified (NOS) with distant metastases [III, A; ESCAT score: II-B].•Analysis for NTRK fusion with NGS or whole genome sequencing is mandatory for differential diagnosis of secretory carcinoma and AcCC [III, A; ESCAT score: I-C].•NGS or whole genome sequencing (or whole exome sequencing) is suggested in recurrent or metastatic (R/M) disease for all tumour subtypes, as actionable mutations or fusion genes can be identified in 40%-50% of patients [V, C]. Clinical classification [cTNM (clinical tumour–node–metastasis)] should be carried out before treatment by the referring physician during initial patient evaluation using the Union for International Cancer Control (UICC) TNM eighth edition staging classification.21O'Sullivan B. Major salivary glands.in: Brierley J.D. Gospodarowicz M.K. Wittekind C. UICC TNM Classification of Malignant Tumours. 8th ed. Wiley-Blackwell, Oxford, UK2017Google Scholar Preoperative diagnostics are mainly based on imaging methods and pathological findings, especially FNA. Pathological staging is carried out after surgical resection of the primary tumour. There is currently no clear recommendation on differential staging of intraparotid versus cervical nodal metastases; findings from a recent study suggest that these differences should be addressed in future editions of the TNM classification.22Lombardi D. Tomasoni M. Paderno A. et al.The impact of nodal status in major salivary gland carcinoma: a multicenter experience and proposal of a novel N-classification.Oral Oncol. 2021; 112105076Crossref PubMed Scopus (15) Google Scholar For correct management of major SGC, the pathological report should follow the International Collaboration on Cancer Reporting guidelines.23Seethala R.R. Altemani A. Ferris R.L. et al.Data set for the reporting of carcinomas of the major salivary glands: explanations and recommendations of the guidelines from the International Collaboration on Cancer Reporting.Arch Pathol Lab Med. 2019; 143: 578-586Crossref PubMed Scopus (13) Google Scholar Operative procedure; specimens submitted; tumour site, focality and dimensions; histological tumour type and grade; perineural invasion; lymphovascular invasion; extent of invasion and margin status are required (see Section 3 of the Supplementary Material, available at https://doi.org/10.1016/j.esmoop.2022.100602).23Seethala R.R. Altemani A. Ferris R.L. et al.Data set for the reporting of carcinomas of the major salivary glands: explanations and recommendations of the guidelines from the International Collaboration on Cancer Reporting.Arch Pathol Lab Med. 2019; 143: 578-586Crossref PubMed Scopus (13) Google Scholar The UICC pathological TNM (pTNM) staging system for SGC of the major salivary glands is presented in Supplementary Table S5, available at https://doi.org/10.1016/j.esmoop.2022.100602. Minor SGCs are staged similarly to SCC, according to the site in which they arise (e.g. oral cavity, pharynx, sinuses, etc.). •Clinical classification should be carried out before treatment and pTNM should be carried out after surgical resection using the UICC eighth edition staging classification [I, A].•Intra-operative frozen sections can be indicated to evaluate margins of resection, perineural invasion and lymph nodes, but only if the result is expected to alter management at the time of surgery [IV, B].•The pathological report should follow the International Collaboration on Cancer Reporting guidelines [III, A]. SGCs are a rare and complicated subgroup of head and neck cancers. As such, local/locoregional disease should be managed by expert surgeons, radiation oncologists, medical oncologists and other specialists working as a multidisciplinary team in specialised head and neck units, such as the centres that are designated members of the European Reference Network on Rare Adult Solid Cancers. Proposed treatment algorithms for the treatment of parotid, minor salivary and sublingual gland, and submandibular gland cancer, are shown in Figures 2, 3 and 4, respectively.Figure 3Treatment algorithm for minor or sublingual SGC. Purple: general categories or stratification; red: surgery; dark green: radiotherapy; white: other aspects of management; blue: systemic anticancer therapy. ChT, chemotherapy; END, elective neck dissection; ND, node dissection; RT, radiotherapy; SGC, salivary gland cancer. aDefinition of high-grade tumours is described in Section 1 of the Supplementary Material, available at https://doi.org/10.1016/j.esmoop.2022.100602.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 4Treatment algorithm for submandibular gland cancer. Purple: general categories or stratification; red: surgery; dark green: radiotherapy; white: other aspects of management; blue: systemic anticancer therapy. ChT, chemotherapy; CNB, core needle biopsy; FNA, fine-needle aspiration; ND, node dissection; RT, radiotherapy. aDefinition of high-grade tumours is described in Section 1 of the Supplementary Material, available at https://doi.org/10.1016/j.esmoop.2022.100602.View Large Image Figure ViewerDownload Hi-res image Download (PPT) The treatment of parotid gland cancer is based on complete surgical excision with free margins.24Lombardi D. McGurk M. Vander Poorten V. et al.Surgical treatment of salivary malignant tumors.Oral Oncol. 2017; 65: 102-113Crossref PubMed Scopus (65) Google Scholar The difficulty of this surgery lies in achieving free margins without functional and aesthetic sequelae. Revision surgery following an unexpected post-operative diagnosis of malignancy carries a great risk to an already dissected facial nerve; therefore, every effort should be made to identify malignancy preoperatively, allowing for immediately adequate surgical removal.25Sood S. McGurk M. Vaz F. Management of salivary gland tumours: United Kingdom National Multidisciplinary Guidelines.J Laryngol Otol. 2016; 130: S142-S149Crossref PubMed Google Scholar It is imperative, if preoperative MRI, FNA or core needle biopsy suggests malignancy, to warn the patient of a possibly more extensive procedure. In case of extraparotid or facial nerve extension, an extended surgery sacrificing these elements [e.g. seventh nerve (nVII), infratemporal fossa, mandible, skin] with possible reconstruction must be considered. Functional or aesthetic disorders arising from resection should be considered during treatment planning.24Lombardi D. McGurk M. Vander Poorten V. et al.Surgical treatment of salivary malignant tumors.Oral Oncol. 2017; 65: 102-113Crossref PubMed Scopus (65) Google Scholar Resectability should be assessed in a multidisciplinary team meeting, bearing in mind that surgery, if possible, is the optimal treatment. A cancer should be considered unresectable if macroscopic tumour is likely to be left behind. The reference procedure is a total parotidectomy. For low-grade, early-stage (cT1-T2N0) tumours in the superficial lobe, a superficial parotidectomy can suffice, especially if malignancy is a post-operative discovery on the definitive histology. For advanced-stage (all but cT1-T2N0) and/or preoperatively known intermediate- or high-grade tumours, a total parotidectomy is preferable. No consensus exists in the literature on how many millimetres thick a margin must be to be considered 'free'. The presence or absence of facial nerve paralysis before surgery influences the choice of procedure: it is logical to try to preserve the facial nerve if there is no preoperative paralysis and to sacrifice it in case of preoperative paralysis.24Lombardi D. McGurk M. Vander Poorten V. et al.Surgical treatment of salivary malignant tumors.Oral Oncol. 2017; 65: 102-113Crossref PubMed Scopus (65) Google Scholar In the absence of preoperative paralysis and in case of intra-operative macroscopic invasion of the facial nerve, sacrifice or preservation of the nerve is decided on a case-by-case basis, depending on the histology of the tumour and extent of invasion of the nerve, as well as the age and wishes of the patient. It is important to collect as much information as possible about the tumour before surgery, discuss scenarios with the patient and be able to do a graft during the ablative procedure. A remote dissection of the nerve branches with an extended resection and frozen section analysis of the nerve section limits may be necessary, especially in AdCC, which is characterised by tumour extensions along and in nerves.26Dillon P.M. Chakraborty S. Moskaluk C.A. et al.Adenoid cystic carcinoma: a review of recent advances, molecular targets, and clinical trials.Head Neck. 2016; 38: 620-627Crossref PubMed Scopus (168) Google Scholar Preoperative facial paralysis is a major negative prognostic factor.24Lombardi D. McGurk M. Vander Poorten V. et al.Surgical treatment of salivary malignant tumors.Oral Oncol. 2017; 65: 102-113Crossref PubMed Scopus (65) Google Scholar It imposes a wide surgery with often unsatisfactory excisional limits. Addressing the nerve deficit during resection is the appropriate therapeutic approach.24Lombardi D. McGurk M. Vander Poorten V. et al.Surgical treatment of salivary malignant tumors.Oral Oncol. 2017; 65: 102-113Crossref PubMed Scopus (65) Google Scholar,27Renkonen S. Sayed F. Keski-Santti H. et al.Reconstruction of facial nerve after radical parotidectomy.Acta Otolaryngol. 2015; 135: 1065-1069Crossref PubMed Scopus (17) Google Scholar Minor SGC, a rare entity, may arise in all mucous membranes of the head and neck (including the nasal cavity, nasopharynx, oropharynx, hypopharynx, cervical oesophagus, larynx, trachea and oral cavity). Cancer of the sublingual gland is 10 times less frequent than minor SGC.9Bradley P.J. McGurk M. Incidence of salivary gland neoplasms in a defined UK population.Br J Oral Maxillofac Surg. 2013; 51: 399-403Abstract Full Text Full Text PDF PubMed Scopus (139) Google Scholar Surgery is the mainstay of treatment for primary resectable disease with the traditional open approach being the most widely used, although endoscopic and robot-assisted approaches have recently been described.28Bollig C.A. Wang K. Llerena P. et al.National analysis of oropharyngeal salivary gland malignancies treated with transoral robotic surgery.Otolaryngol Head Neck Surg. 2022; 166: 886-893Crossref PubMed Scopus (1) Google Scholar In a series of 450 patients with minor SGC, multivariate analysis showed advanced clinical stage and unfavourable histological subtype to be associated with poor disease-specific survival.29Hay A.J. Migliacci J. Karassawa Zanoni D. et al.Minor salivary gland tumors of the head and neck-Memorial Sloan Kettering experience: incidence and outcomes by site and histological type.Cancer. 2019; 125: 3354-3366Crossref PubMed Scopus (59) Google Scholar This was confirmed in a large Surveillance, Epidemiology and End Results (SEER) database study of 1426 patients with minor SGC of the oropharynx.30Goel A.N. Badran K.W. Braun A.P.G. et al.Minor salivary gland carcinoma of the oropharynx: a population-based analysis of 1426 patients.Otolaryngol Head Neck Surg. 2018; 158: 287-294Crossref PubMed Scopus (15) Google Scholar It is generally accepted that a 1-cm free margin is adequate in most tumours; however, it is often the case that only millimetric margins are achievable. AdCC is particularly known for perineural spread (as described earlier), requiring detailed surgical planning and wide margins, including resection of bony structures.24Lombardi D. McGurk M. Vander Poorten V. et al.Surgical treatment of salivary malignant tumors.Oral Oncol. 2017; 65: 102-113Crossref PubMed Scopus (65) Google Scholar The most common submandibular gland malignant tumour type is AdCC.31Han M.W. Cho K.J. Roh J.L. et al.Patterns of lymph node metastasis and their influence on outcomes in patients with submandibular gland carcinoma.J Surg Oncol. 2012; 106: 475-480Crossref PubMed Scopus (26) Google Scholar,32Aro K. Tarkkanen J. Saat R. et al.Submandibular gland cancer: specific features and treatment considerations.Head Neck. 2018; 40: 154-162Crossref PubMed Scopus (23) Google Scholar Tumours confined within the submandibular gland require resection of the gland and the surrounding level Ib lymph nodes to ensure negative margins. In case of high-grade malignancy without clinical evidence of cervical lymph node involvement, selective neck dissection involving level I, II and III lymph nodes is standard procedure as the prevalence of cervical lymph node metastasis in submandibular gland malignancies is high, exceeding that of the parotid malignancies.24Lombardi D. McGurk M. Vander Poorten V. et al.Surgical treatment of salivary malignant tumors.Oral Oncol. 2017; 65: 102-113Crossref PubMed Scopus (65) Google Scholar,32Aro K. Tarkkanen J. Saat R. et al.Submandibular gland cancer: specific features and treatment considerations.Head Neck. 2018; 40: 154-162Crossref PubMed Scopus (23) Google Scholar,33Vander Poorten V.L. Balm A.J. Hilgers F.J. et al.Prognostic factors for long term results of the treatment of patients with malignant submandibular gland tumors.Cancer. 1999; 85: 2255-2264Crossref PubMed Scopus (72) Google Scholar Careful surgical planning is needed for AdCC, as clear margin surgery may require resection of important structures such as the lingual, hypoglossal and marginal mandibular nerves, floor of the mouth muscles and the skin. Although the risk of nodal metastasis in AdCC is low, this tumour has a propensity for infiltrating the adjacent lymph nodes and perineural spread.24Lombardi D. McGurk M. Vander Poorten V. et al.Surgical treatment of salivary malignant tumors.Oral Oncol. 2017; 65: 102-113Crossref PubMed Scopus (65) Google Scholar,31Han M.W. Cho K.J. Roh J.L. et al.Patterns of lymph node metastasis and their influence on outcomes in patients with submandibular gland carcinoma.J Sur
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