Metastasising pleomorphic adenoma: Systematic review

International Journal of Surgery 19 (2015) 137e145

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Original research

Metastasising pleomorphic adenoma: Systematic review James Knight a, *, Kumaran Ratnasingham b a b

Department of Medicine, St George's University of London, Cranmer Terrace, London, SW17 0RE, UK Department of General Surgery, Royal Surrey County Hospital, UK

h i g h l i g h t s 81 cases were found. Mean age at diagnosis of MPA was 49.5 years. Most common sites for MPA were: bone 36.6%, lung 33.8% and neck lymph nodes. Site of primary PA included 74.1% parotid, 14.8% submandibular. 20.1% (n ¼ 17).80.4%) were alive at least at 1-year.

a r t i c l e i n f o

a b s t r a c t

Article history: Received 2 January 2015 Received in revised form 8 April 2015 Accepted 28 April 2015 Available online 6 May 2015

Background: Pleomorphic adenoma (PA) is the commonest benign neoplasm of salivary glands.1 PA can undergo malignant transformation to ex-pleomorphic adenoma 2,3 but rarely, can metastasise without malignant transformation.4,5 Metastasising pleomorphic adenoma (MPA) is a rare malignant tumour which, histologically, is indistinguishable from PA yet produces secondary tumours in distant sites.6,7,8 Objective: Our aim is to review the literature for all reported cases of MPA and create a virtual series. The age and location of primary tumour with the location and time to metastasise will be reviewed. The prognosis and treatment options will be explored. Method: We conducted a PUBMED search with a combination of keywords: metastasizing/metastasising AND pleomorphic adenoma OR mixed tumour. An author's own case has also been included. Results: Between 1942 and 2014 there were 80 case reports included in the review, plus the authors own case. Mean age at diagnosis of MPA was 49.5 years (range 11e83). Male-to-female ratio was 34:46. The mean time between PA and MPA was 14.9 years (range 0e51), with three cases reporting simultaneous presentation. 72.8% (n ¼ 59) of cases reported PA local recurrence prior to MPA. The three most common sites for MPA were: bone 36.6% (n ¼ 28), lung 33.8% (n ¼ 26) and neck lymph nodes 20.1% (n ¼ 17). Survival was poorly reported, but 41 (80.4%) were alive at 1-year. Conclusion: Benign MPA is rare. Metastasis occurs years after the initial PA and is associated with multiple local recurrences. Histologically, MPA retain their benign nature yet demonstrate malignant behaviour. © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

Keywords: Metastasising pleomorphic adenoma Systematic review

1. Introduction Pleomorphic adenoma (PA) is the commonest benign neoplasm of salivary glands [1]. PA can undergo malignant transformation to

* Corresponding author. E-mail address: [email protected] (J. Knight).

ex-pleomorphic adenoma [2,3] but rarely, can metastasise without malignant transformation [4,5]. Metastasising pleomorphic adenoma (MPA) is a rare malignant tumour which, histologically, is indistinguishable from PA yet produces secondary tumours in distant sites [6e8]. Little is known regarding the disease course and prognosis of MPA. The most up-to-date literature review included case reports prior to 2010 [1]. However, there are no systematic reviews of MPA in the literature.

http://dx.doi.org/10.1016/j.ijsu.2015.04.084 1743-9191/© 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

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J. Knight, K. Ratnasingham / International Journal of Surgery 19 (2015) 137e145

1.1. Objective Our aim was to systematically review the literature for all reported cases of MPA. The age and location of primary tumour with the location and time to metastasise was reviewed. The prognosis and treatment options were explored. 2. Methods 2.1. Search strategy We carried out an English language literature search using the PUBMED database to identify MPA case reports, also known as mixed tumours. We also included a case of our own, reported in Appendix 1, under Knight. As MPA are rare, there was no limitation to the time period for our search, which resulted in cases being included from 1942 to 2014. We searched for the following keywords: metastasizing/metastasising AND pleomorphic adenoma OR mixed tumour, and also conducted a reference check of the articles found for further reported cases. 2.2. Inclusion and exclusion criteria We included: All case reports regarding metastasising pleomorphic adenomas or mixed tumours. Articles reporting literature reviews of MPA or metastasising mixed tumours. Case reports written in English. Case reports from any time period. Our exclusion criteria were: Carcinoma ex-pleomorphic adenoma or metastasizing malignant PA. Articles published in languages other than English. Pleomorphic adenomas with local recurrence, but no distant metastasis.

2.3. Data extraction Two reviewers extracted all data independently using a data extraction sheet. For each case report included in the review, we collated information (where available) regarding: year of publication, author, patient demographics, primary PA, MPA, local recurrences, treatment received and outcome.

2.4. Risk of bias in individual case reports The most significant potential bias is the requirement for authors to accurately diagnose and report truly benign MPA. Where available, the histology and cytology reports, along with any other relevant material, were studied by both reviewers for features of carcinoma ex-pleomorphic adenoma (CEPA) or any other malignant features. If found, these cases were excluded, as per exclusion criteria. 3. Results Our search strategy found 186 papers. 139 were excluded as per exclusion criteria leaving 47. 17 further papers were found via

Fig. 1. Literature search results showing numbers of papers found, included and excluded. Some papers contained multiple case reports. We included 64 papers in the review with a total of 81 case reports.

secondary references. This gave a total of 64 papers included in the study. Some papers reported multiple cases of MPA, giving a total of 81 case reports [Fig. 1]. Mean age at diagnosis of MPA was 49.5 years (range 11e83). Male-to-female ratio was 34:46, one case did not report gender. The mean time interval between PA and MPA was 14.9 years (range 0e51), with two cases reporting simultaneous presentation of PA and MPA [Table 1, Fig. 2]. Site of primary PA included 60 (74.1%) parotid gland, 12 (14.8%) submandibular, 5 (6.2%) soft or hard palate, 2 (2.5%) nasal septum and 1 (1.2%) tongue [Fig. 3]. There was also one case, reported by Klijankjenko et al. of a lung primary which metastasised to breast and paravertebral regions. In our virtual series we found the local recurrence rate prior to MPA [8] to be 72.8% (59). The three most common sites for MPA were bone 36.6% (n ¼ 28), lung 33.8% (n ¼ 26) and cervical lymph nodes 20.1% (n ¼ 17) [Fig. 4]. Other sites included renal 8.6% (n ¼ 7), cutaneous 8.6% (n ¼ 7), hepatic 4.9% (n ¼ 7) and brain 3.7% (n ¼ 3); also reported were cases of: sinus, retroperitoneal, abdominal wall, pharynx, mediastinum, and breast. 40.7% (n ¼ 33) of MPA cases showed multiple sites of metastasis, for instance lung and hepatic, or renal and bone. Of the 59.3% (n ¼ 48) MPAs which showed a single metastasis we included cases with multiple lymph node involvement if they were contained within one anatomical nodal region (e.g. left cervical nodes); there were 14 (20.1%) such cases.

3.1. Survival Survival was not well documented, primarily as long term follow-up was not discussed and case reports were mostly published relatively soon after treatment of MPA. Of the 81 cases studied, 51 (62.9%) reported survival or disease free periods. Of those, 9 (17.6%) had died from MPA and 11 (21.6%) remained alive with disease for periods ranging 12e84 months. 40 (78.4%) cases reported a disease-free period, but did not report further follow-up. Therefore, it was not possible to calculate accurate survival rates for MPA. We can, however, report the proportions who were alive at any given time period, though their actual survival time cannot be shown. Of the 51 (62.9%) cases which reported time to death or disease-free periods we know that 41 (80.4%) were alive at 1-year.


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Table 1 Age at presentation for primary PA, MPA and time interval between PA and MPA. Years

Age of primary PA (%)

Age of MPA (%)

Interval between PA to MPA (%)

20yrs 1

NR NR 6 30 6 NR 24 NR NR NR

10


Klijankjenko et al [51]

KEY NT ¼ Not treated. NR ¼ Not Reported. M ¼ Multiple. S ¼ Simultaneous (PA and MPA presented). MPA ¼ Metastasising pleomorphic adenoma. LR ¼ Local recurrence. 143

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