British Journal of Oral and Maxillofacial Surgery (2004) 42, 195—199
Polymorphous low-grade adenocarcinoma–—a rareand aggressive entity in adolescence
M. Kumara,c,*, N. Stivarosa, A.W. Barrettb, G.J. Thomasb,G. Boundsc, L. Newmana
a Maxillofacial Unit, University College Hospital, London WC1E 6AU, UKb Oral and Maxillofacial Pathology Unit, Eastman Dental Institute, University College London,University of London, Gray’s Inn Road, London WC1X 8LD, UKc Department of Oral and Maxillofacial Surgery, Central Middlesex Hospital, Acton Lane,London NW10 7NS, UK
The term polymorphous low-grade adenocarcinoma(PGLA) was first coined by Evans and Batsakis1 in1984 to describe a type of salivary gland tumourthat showed a many growth patterns, but cytolog-ical uniformity. In most cases the minor salivaryglands are affected2,3 the commonest site beingthe palate.4,5 Diagnostic difficulties centre aroundthe resemblance of some PLGA to pleomorphic ade-noma or adenoid cystic carcinoma. The latter, mayshow cribriform morphology and perineural infiltra-
tion, and distinguishing the two may be difficultin a small biopsy specimen. However, this distinc-tion is important, as it may affect treatment andprognosis.2,6 PLGA generally has a good prognosis,though local recurrence and lymph node metastasismay develop and the tumour must be completelyexcised.2,3 Recently, some morphological charac-teristics have been suggested that may determinethose PLGA that may not, be low grade, and neo-plasms with a papillary cystic pattern fall into thiscategory.3 Larger series of PLGA suggest that thistumour does not occur in patients under the age of20 years of age,2,3 but here we describe a case ofPLGA that first presented in a 14-year-old girl andit did not behave in a low-grade fashion. Papillarycystic growth pattern and tumour necrosis becamemore prominent as her course progressed.
Figure 1 Right posterior palatal lesion, extending tothe midline and onto the soft palate.
Case report
Whilst living abroad, a 14-year-old female, whowas generally fit and well, noticed a painless smalllump in the right side of the palate (Fig. 1). This wasobserved by her orthodontist for several monthswithout intervention. Two years later, on returningto the United Kingdom, the patient presented witha lump located at the junction of the right hardand soft palate. She reported that it was increasingin size. An incisional biopsy was performed and a
Figure 2 Coronal MRI scan shows localised right palatallesion (arrow).
Figure 3 Axial computed tomogram shows right maxil-lary lesion (arrow).
diagnosis of adenoid cystic carcinoma was made.Magnetic resonance imaging (MRI) showed a lo-calised lesion in the palate with no lymphadenopa-thy (Fig. 2). Computerised tomography (CT) ofthe chest and abdomen showed no abnormality.The incisional biopsy was reviewed at this time by
Figure 4 Axial MRI scan shows right infratemporal fossalesion (arrow).
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specialist oral pathologists and the diagnosis revisedto PLGA. The tumour was widely excised and thediagnosis of PLGA confirmed histologically. Excisionof the tumour was histologically incomplete, but asthere was no clinical evidence of tumour no furthersurgery was carried out immediately, and she wasmonitored frequently. She remained well for 10months, but then developed a swelling and discom-fort in the right side of the maxilla with mobility of17. This was extracted, and microscopic examina-tion of granulation tissue from the socket revealedmore tumour. The ipsilateral jugulo-digastic lymphnode was enlarged, but fine needle aspiration re-vealed only reactive changes. CT scan imagingshowed a large mass in the right maxilla (Fig. 3).The patient underwent further surgery with a
right posterior partial maxillectomy, supra-omohy-oid neck dissection, and reconstruction with a leftradial forearm free flap. Per-operative frozen sec-tions were negative, but definitive histopathologyagain showed positive margins and metastatic de-positis of tumour were identified in level II cervicallymph nodes. In view of this, she underwent six cy-cles of cisplatin and external beam radiotherapy tothe primary site and neck. She developed trismus,and 5 months later underwent manipulation of themandible under a general anaesthetic. Biopsy atthis time showed no evidence of tumour, however,3 months on there was no clinical improvement inthe mouth opening, and MRI showed a large massin the right infratemporal fossa (Fig. 4). A furtherresection was carried out, and tumour was found inthe right medial pterygoid muscle, posterior max-illa, nasal space, the deep aspect of the skin flap,and the medullary spaces of the right coronoidprocess. A fresh reconstruction with a right radialforearm free flap was placed in the defect. Shedeveloped osteoradionecrosis of the mandible andtwo submandibular sinuses, but has now been tu-mour free for 18 months. She remains on long-termfollow-up.
Histopathology
The incisional biopsy and first resection showeda partially circumscribed, lobular but infiltrative
Figure 5 Initial palatal tumour showing variable growthpattern with lobular, tubular, trabecular cribriform andsingle-file arrangements of neoplastic cells (a, field width8mm). The tumour is invading and destroying the mu-cous acini of the palatal salivary glands (b, field width2mm) and shows both peri- and intraneural infiltration(c, field width 2mm). Haematoxylin and eosin (originalmagnification 25×).
198 M. Kumar et al.
neoplasm with a variable growth pattern (Fig. 5a).This was composed of sheets, islands, trabeculaeand single cell strands of malignant epithelial cellsin a hyaline or mucinous stroma. Occasional cribri-form or papillary cystic areas were also observed.The tumour cells had sparse basophilic cytoplasmwith indistinct margins and large vesicular nuclei.There was minimal necrosis and cell atypia, a mi-totic count of 3/10 high power fields (HPF), inva-sion of striated muscle and minor salivary glands(Fig. 5b), and both peri- and intraneural infiltration(Fig. 5c).One year later, the neoplasm had similar histo-
logical features, but the papillary cystic growthpattern was more prominent and several tumour is-lands showed central necrosis (Fig. 6). Mitoses were
Figure 6 First tumour recurrence. There are prominentpapillary cystic areas (a) and central necrosis of the tu-mour islands (b). Haematoxylin and eosin (field width0.5mm, original magnification 100×).
Figure 7 Metastatic tumour deposit in a level II cervicallymph node. Haematoxylin and eosin (field width 2mm,original magnification 100×).
seen at a frequency of 2/10 HPF. The metastaticdeposit was similar to the original histology (Fig. 7).The third resection revealed a tumour that was his-tologically high grade, with extensive papillary cys-tic change and necrosis. The mitotic rate was 1/10HPF. Other growth patterns often seen in PLGA werevirtually lost. There was also radiation damage.
Discussion
To our knowledge, this is the youngest reportedcase of PGLA, the mean age of presentation being inthe sixth decade with a female preponderance.2,3
Previous series indicate the frequency of local re-currence is 9—33%,1—3,7—11 with regional lymphnode metastasis in 6—35%.1,3,7,9,11,12 Metastasesto the paraoesophageal lymph nodes, lungs, orbitand skin have been reported, but overall distantmetastases develop in less than 1% of cases.7,13—15
In the largest series of 164 cases,2 98% of patientswere either alive, or had died with no evidenceof recurrence, over a mean follow-up period of115 months. Nevertheless, deaths due to PLGA hasbeen reported.3,11,16 Most however, follow an indo-lent course, but because of anomalous high gradelesions it has been suggested that ‘‘low grade’’ bedropped from the name.17
What histological features might indicate a tu-mour destined to behave more aggressively? Inassessing 40 PLGA, Evans and Luna3 reported asignificant relationship between a papillary cysticgrowth pattern (Fig. 5) and cervical lymph nodemetastases (Fig. 6), and we recommend that, ifpapillary cystic change is prominent in a PLGA,
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the surgeon be alerted to the possibility of aggres-sive behaviour. The relationship between invadedsurgical margins and local recurrence was also sig-nificant, but necrosis, mitotic rate, bone and per-ineural invasion were not.6 It is uncertain whetherthe aggressive behaviour of the neoplasm in ourpatient was inherent and inevitable, associatedwith her youth, or the result of frequent surgicalintervention.The most appropriate treatment for PLGA is
wide local excision, with invaded surgical mar-gins an indication for further excision. Adjuvantchemo-therapy and radiotherapy was of little ben-efit in our case, as has been reported in otherPLGA.10,11,16,18
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