Sinonasal tract and nasopharynx

Adenocarcinomas arising in the paranasal sinuses and nasal cavity (sinonasal tract) and nasopharynx may be categorised into those arising from the surface (i.e. intestinal and non-intestinal-type sinonasal adenocarcinomas) and those arising from the mucoserous or minor salivary-type glands. While sinonasal tract carcinomas are uncommon overall, adenoid cystic carcinoma is the most common salivary-type adenocarcinoma in this anatomical location. Adenoid cystic carcinoma may arise in patients of a wide age range (mean age of 50–60 years), and affects men and women at similar rates.Reference Thompson, Penner, Ho, Foss, Miettinen and Wieneke ^{2 ,} Reference Lupinetti, Roberts, Williams, Kupferman, Rosenthal and Demonte ³

Adenoid cystic carcinoma in the sinonasal tract arises most often from the maxillary sinus, and presents as early stage (I or II) disease in approximately 50 per cent of cases.Reference Thompson, Penner, Ho, Foss, Miettinen and Wieneke ² Histologically, adenoid cystic carcinoma in this location is similar to what is encountered in salivary glands, growing as a biphasic population of luminal and non-luminal cells, arranged in tubules, cribriform structures and solid nests, with frequent perineural invasion. Adenoid cystic carcinoma can be misclassified in this location, however, possibly because it may be unexpected.Reference Thompson, Penner, Ho, Foss, Miettinen and Wieneke ²

Sinonasal tract adenoid cystic carcinoma is often managed with surgery, with or without external beam radiation therapy. Survival rates are similar to those for major salivary gland tumours, with 5-year and 10-year overall survival rates of approximately 65 per cent and 40–50 per cent, respectively.Reference Thompson, Penner, Ho, Foss, Miettinen and Wieneke ^{2 –} Reference Sanghvi, Patel, Patel, Kalyoussef, Baredes and Eloy ⁴

Case reports of lymph node metastasis have been summarised in Table I.Reference Thompson, Penner, Ho, Foss, Miettinen and Wieneke ^{2 ,} Reference Lupinetti, Roberts, Williams, Kupferman, Rosenthal and Demonte ^{3 ,} Reference Pitman, Prokopakis, Aydogan, Segas, Carrau and Snyderman ^{5 –} Reference Seong, Hyun, Kim, Cho, Lee and Yoon ¹³ Most papers reported up to 3 patients with lymph node metastases, except the article by Amit et al. which included 13 patients with lymph node metastases.Reference Amit, Binenbaum, Sharma, Ramer, Ramer and Agbetoba ⁹

Table I Cases of paranasal sinus, nasal cavity and nasopharyngeal adenoid cystic carcinoma with lymph node metastasis

*‘Neck’ and ‘regional’ recurrences are presented (no further data are provided).

In a recent report by Thompson et al., all but 1 of 86 patients with sinonasal tract adenoid cystic carcinoma had clinically node-negative (N₀) necks at the time of presentation, while 70 patients were subjected to elective neck dissection (lymph node sampling, sentinel lymph node biopsy or modified radical neck dissection).Reference Thompson, Penner, Ho, Foss, Miettinen and Wieneke ² Of the 86 patients, only 3 presented with distant metastatic disease at initial clinical evaluation. Two of these three patients had disease to bone and one had disease to the lungs; all three patients had clinically staged N₀ necks. The one patient with a neck mass at presentation showed only benign reactive lymphoid hyperplasia of the lymph nodes sampled.Reference Thompson, Penner, Ho, Foss, Miettinen and Wieneke ^{2 ,} Reference Toluie and Thompson ¹⁴ Two patients who developed high-grade transformation lacked lymph node metastasis at presentation, but both died with locally recurrent and metastatic disease less than one year after initial presentation.Reference Thompson, Penner, Ho, Foss, Miettinen and Wieneke ² In sinonasal tract adenoid cystic carcinoma, bone invasion (p = 0.005), perineural invasion (p < 0.0001) and lymphovascular invasion (p = 0.006) were all found to be statistically significantly correlated with a worse patient outcome, but not with lymph node disease.Reference Thompson, Penner, Ho, Foss, Miettinen and Wieneke ² Similarly, even though many patients presented with a pathologically staged T₃ or T₄ (advanced stage) primary tumour, these patients did not present with lymph node metastases. Therefore, this group of patients presented with primarily local disease only (i.e. no lymph node or distant metastasis), a finding confirmed in other studies.Reference Lupinetti, Roberts, Williams, Kupferman, Rosenthal and Demonte ^{3 ,} Reference Pitman, Prokopakis, Aydogan, Segas, Carrau and Snyderman ⁵ Nevertheless, local disease does not imply early stage disease. In fact, the majority of patients present with advanced stage disease according to pathologically staged T classification.

In a study reporting on outcomes of skull base surgery in patients with sinonasal tract adenoid cystic carcinoma, Pitman et al. found that 0 of 35 patients had regional metastases on presentation.Reference Pitman, Prokopakis, Aydogan, Segas, Carrau and Snyderman ⁵ Six of the 35 patients subsequently developed ‘regional recurrences’, but additional details were not provided. Similarly, a 40-year review article by Wiseman et al. reported 1 patient with a ‘neck recurrence’ among 35 cases of adenoid cystic carcinoma, though further data are not provided.Reference Wiseman, Popat, Rigual, Hicks, Orner and Wein ⁶ Amit et al. conducted a meta-analysis of sinonasal tract adenoid cystic carcinomas.Reference Amit, Binenbaum, Sharma, Ramer, Ramer and Agbetoba ⁹ Of the 41 patients subjected to neck dissection (from a cohort of 99 patients treated between 1985 and 2011 in 9 cancer centres worldwide), 13 (13 per cent) had regional lymph node metastases.Reference Amit, Binenbaum, Sharma, Ramer, Ramer and Agbetoba ⁹

Husain et al. conducted a meta-analysis of the literature on sinonasal tract adenoid cystic carcinoma published up to 2012, which included 88 individual cases and aggregated data on 366 patients.Reference Husain, Kanumuri, Svider, Radvansky, Boghani and Liu ¹⁵ The authors concluded that surgery of the primary tumour, with radiation and/or chemotherapy, is generally employed, and is possibly the most effective therapy. However, data regarding lymph node dissection or lymph node sampling were not included. Likewise, a large analysis of the Surveillance, Epidemiology, and End Results registry was conducted for sinonasal tract adenoid cystic carcinoma,Reference Sanghvi, Patel, Patel, Kalyoussef, Baredes and Eloy ⁴ but does not include data regarding lymph node status or lymph node sampling.

Overall, the available information indicates that lymph node metastasis of adenoid cystic carcinoma from the sinonasal tract and nasopharynx is relatively uncommon, suggesting that elective neck lymph node dissection is not advisable.

Lacrimal gland

Tumours of the lacrimal gland are rare, but adenoid cystic carcinoma is the most common malignant epithelial neoplasm therein.Reference Font, Smith and Bryan ^{16 –} Reference Font, Croxatto and Rao ¹⁸ Adenoid cystic carcinoma generally affects adults (with a mean age of 40 years),Reference von Holstein, Rasmussen and Heegaard ¹⁹ but can arise in children as young as 6 years.Reference Font, Croxatto and Rao ^{18 ,} Reference Lee, Campbell, Waller and IIstrup ^{20 –} Reference Wright, Rose and Garner ²² Patients with adenoid cystic carcinoma of the lacrimal glands present with short histories of eye-related symptoms such as pain, diplopia and ptosis.Reference Font, Croxatto and Rao ^{18 ,} Reference Lee, Campbell, Waller and IIstrup ^{20 ,} Reference Wright, Rose and Garner ²² In this location, adenoid cystic carcinoma is essentially identical to what is encountered in the major salivary glands and other sites.Reference Font, Croxatto and Rao ^{18 ,} Reference Gamel and Font ²³ The majority of lacrimal gland adenoid cystic carcinomas are high-grade (solid/basaloid) phenotype which translates into a more aggressive clinical course and shorter median survival of only 2.5 years compared to other sites of origin.Reference Li, Xu, Zhao, El-Naggar and Sturgis ^{24 ,} Reference Esmaeli, Ahmadi, Youssef, Diba, Amato and Myers ²⁵ Indeed, even with aggressive therapy including radical resection and/or external beam radiation, the recurrence rate is as high as 75 per cent.Reference Font, Croxatto and Rao ^{18 ,} Reference Wright, Rose and Garner ²² Most patients eventually experience distant metastases, most frequently to the lung, and the 10-year survival is approximately 50 per cent.Reference Li, Xu, Zhao, El-Naggar and Sturgis ^{24 –} Reference Sali, Yadav, Bushan, Rajpurohit, Varty and Sharma ²⁶ Outcomes are improved in children and in tumours that lack a component of solid growth.Reference Font, Croxatto and Rao ^{18 ,} Reference Tellado, McLean, Specht and Varga ^{21 ,} Reference Gamel and Font ²³

Most series of lacrimal gland adenoid cystic carcinoma have not specifically commented on the rate of documented regional lymph node metastases (including intraparotid gland lymph nodes), but these appear to be uncommon (Table II).Reference Esmaeli, Ahmadi, Youssef, Diba, Amato and Myers ^{25 ,} Reference Friedrich and Bleckmann ^{27 –} Reference Sanders, Mendenhall and Werning ³⁰ Interestingly, metastases to lacrimal glands from the parotid gland have been reported; thus, when encountering adenoid cystic carcinoma of the lacrimal glands, metastasis from a primary major salivary gland must be excluded.Reference Klijanienko, El-Naggar, Servois, Rodriguez, Desjardins and Schlienger ³¹ Douglas et al. reviewed 151 patients with adenoid cystic carcinoma of the head and neck, including 32 cases of adenoid cystic carcinoma of the paranasal sinuses, 15 of the nasopharynx and 7 of the lacrimal glands.Reference Douglas, Laramore, Austin-Seymour, Koh, Stelzer and Griffin ³² They analysed all the locations together and concluded that ‘at 5 years, 50 per cent of lymph node positive patients had developed distant metastases compared to 26 per cent (p < 0.001) of lymph node negative patients’.

Table II Cases of lacrimal gland adenoid cystic carcinoma with lymph node metastasis

External auditory canal

The external auditory canal, which spans the space between the auricle and the tympanic membrane, may give rise to a variety of both benign and malignant tumours. The great majority (over 90 per cent) of external auditory canal malignancies prove to be squamous cell carcinomas and basal cell carcinomas; less than 5 per cent are adenoid cystic carcinomas.Reference Perzin, Gullane and Conley ^{33 ,} Reference Koopot, Reyes and Pifarre ³⁴

Adenoid cystic carcinoma of the external auditory canal is presumed to arise from the apocrine-type ceruminous glands. It is regarded as one of the subtypes of ‘ceruminous adenocarcinoma’, comprising the glandular-derived malignant tumours of the external auditory canal.Reference Crain, Nelson, Barnes and Thompson ³⁵ These tumours most often present with ear pain, mass and/or hearing changes, with a mean age at presentation within the fifth decade of life. While the rarity of these lesions in this location limits analysis, there are rare instances of metastatic disease to cervical lymph nodes, with approximately 11 per cent of cases showing clinically occult disease.Reference Perzin, Gullane and Conley ^{33 ,} Reference Dong, Gidley, Ho, Luna, Ginsberg and Sturgis ^{36 –} Reference Liu, Kang, Nieh, Chang and Wang ³⁹ Diagnostic criteria include exclusion of extension from a salivary gland (parotid gland) primary, by clinical assessment, imaging or gross examination.

Adenoid cystic carcinomas arising in the external auditory canal appear to be aggressive tumours and are usually treated by wide local resection, with possible adjuvant radiotherapy. Local recurrences have been reported in 40–60 per cent of patients, and have been detected as long as 15 years after initial diagnosis. Death from this disease is most often attributed to intracranial spread of tumour or distant metastasis (in particular, involving the lung),Reference Perzin, Gullane and Conley ^{33 ,} Reference Dong, Gidley, Ho, Luna, Ginsberg and Sturgis ³⁶ rather than from metastatic disease to lymph nodes.

Authorship

This article was written by members and invitees of the International Head and Neck Scientific Group (www.IHNSG.com): J A Bishop, Departments of Pathology, and Otolaryngology – Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA; K O Devaney, Department of Pathology, Allegiance Health, Jackson, Michigan, USA; L Barnes, Department of Pathology, University of Pittsburgh School of Medicine, Pennsylvania, USA; P J Slootweg, Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands; A Cardesa, Department of Anatomic Pathology, Hospital Clinic, University of Barcelona, Spain; D R Gnepp, University Pathologists, Providence, Rhode Island, and Fall River, Massachusetts, USA; M D Williams, Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, USA; A Triantafyllou, Oral and Maxillofacial Pathology, School of Dentistry, University of Liverpool, and Cellular Pathology, Liverpool Clinical Laboratories, UK; R de Bree, Department of Head and Neck Surgical Oncology, UMC Utrecht Cancer Center, University Medical Center Utrecht, The Netherlands; K T Robbins, Division of Otolaryngology – Head and Neck Surgery, Southern Illinois University School of Medicine, Springfield, USA; A Coca-Pelaz, Department of Otolaryngology, Hospital Universitario Central de Asturias, Oviedo, Spain; V Vander Poorten, Otorhinolaryngology – Head and Neck Surgery and Department of Oncology, Section Head and Neck Oncology, University Hospitals Leuven, Katholieke Universiteit Leuven, Belgium, and European Salivary Gland Society, Geneva, Switzerland; C Suárez, Fundación de Investigación e Innovación Biosanitaria del Principado de Asturias, Oviedo, Spain; J P Shah, Head and Neck Surgery, Memorial Sloan Kettering Cancer Center, New York, USA; P J Bradley, European Salivary Gland Society, Geneva, Switzerland, and Department of Otolaryngology – Head and Neck Surgery, Nottingham University Hospitals, Queens Medical Centre Campus, UK; L P Kowalski, Department of Head and Neck Surgery and Otorhinolaryngology, A C Camargo Cancer Center, São Paulo, Brazil; C E Silver, Department of Surgery, University of Arizona College of Medicine, Phoenix, USA; J P Rodrigo, Department of Otolaryngology, Hospital Universitario Central de Asturias, Oviedo, and Instituto Universitario de Oncología del Principado de Asturias, University of Oviedo, Spain; K T Pitman, Department of Surgery, Banner MD Anderson Cancer Center, Gilbert, Arizona, USA; A Teymoortash, Department of Otolaryngology – Head and Neck Surgery, Philipp University, Marburg, Germany; J A Eloy, Department of Otolaryngology – Head and Neck Surgery, Neurological Institute of New Jersey, Rutgers New Jersey Medical School, Newark, USA; R P Takes, Department of Otolaryngology – Head and Neck Surgery, Radboud University Medical Center, Nijmegen, The Netherlands; M Hamoir, Department of Head and Neck Surgery, Head and Neck Oncology Program, St Luc University Hospital, and King Albert II Cancer Institute, Brussels, Belgium; J E Medina, Department of Otorhinolaryngology, University of Oklahoma Health Sciences Center, Oklahoma City, USA; W M Mendenhall, Department of Radiation Oncology, University of Florida, Gainesville, USA; P Strojan, Department of Radiation Oncology, Institute of Oncology, Ljubljana, Slovenia; H Hellquist, Department of Biomedical Sciences and Medicine, University of Algarve, Faro, Portugal; A Skálová, Department of Pathology, Charles University in Prague, Faculty of Medicine in Plzen, Czech Republic; A Rinaldo, University of Udine School of Medicine, Italy; A Ferlito, Co-ordinator of the International Head and Neck Scientific Group.