Orbit

The International Journal on Orbital Disorders, Oculoplastic and

Lacrimal Surgery

ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/iorb20

Squamous carcinoma ex pleomorphic adenoma of

the lacrimal gland

Huzaifa Malick , Reena Kumari , Vangelis Lokovitis , Hardeep-Singh Mudhar ,

Ram Vaidhyanath & Raghavan Sampath

To cite this article: Huzaifa Malick , Reena Kumari , Vangelis Lokovitis , Hardeep-Singh Mudhar ,
Ram Vaidhyanath & Raghavan Sampath (2020): Squamous carcinoma ex pleomorphic adenoma of
the lacrimal gland, Orbit, DOI: 10.1080/01676830.2020.1841807

To link to this article: https://doi.org/10.1080/01676830.2020.1841807

Published online: 10 Nov 2020.

Submit your article to this journal

Article views: 23

View related articles

View Crossmark data

Full Terms & Conditions of access and use can be found at

https://www.tandfonline.com/action/journalInformation?journalCode=iorb20
ORBIT
https://doi.org/10.1080/01676830.2020.1841807

CASE REPORT

Squamous carcinoma ex pleomorphic adenoma of the lacrimal gland

Huzaifa Malick a, Reena Kumaria, Vangelis Lokovitisa, Hardeep-Singh Mudharb, Ram Vaidhyanatha,
and Raghavan Sampatha
a
Ophthalmology Department, University Hospitals of Leicester, Leicester, UK; bNational Specialist Ophthalmic Pathology Service (NSOPS), Royal
Hallamshire Hospital, Sheffield, UK

ABSTRACT ARTICLE HISTORY

We present a very rare case of squamous cell carcinoma (SCC) ex pleomorphic adenoma of the Received 16 August 2020
lacrimal gland. Our patient presented with a 12 month history of painful proptosis of his left eye Accepted 18 October 2020
associated with severe headache. Imaging showed a left lacrimal gland lesion with extensive orbital KEYWORDS
disease extending into lateral and superior rectus muscles, cavernous sinus and the greater wing of Orbit; pleomorphic
the sphenoid. A lacrimal gland biopsy showed a combination of small bland glandular structures adenoma; squamous
and sclerotic, elastin-containing stroma showing that the SCC had arisen on a background of carcinoma
a probable pleomorphic adenoma. Treatment with cisplatin and 5-Fluorouracil proved efficacious
with a significant reduction of orbital and post-orbital disease on interval scanning.

We present a very rare case of squamous cell carcinoma
(SCC) ex pleomorphic adenoma (PA) of the lacrimal gland
with only one previously documented case in the literature
of primary SCC ex PA involving the lacrimal gland.1
A 50-year old gentleman presented with a 12-
month history of painful proptosis of his left eye
associated with severe headaches. Clinically hypoglo­
bus, proptosis and tender swelling of the lacrimal
gland were noted. Restriction of abduction and resis­
tance to retropulsion was noted in the affected eye
associated with sensory deficit in the V1 and V2
region of the trigeminal nerve. The rest of the ocular
examination was within normal limits. No lymphade­
nopathy or other systemic signs or symptoms were
noted. Radiologically an extraconal orbital mass was
noted with subtle erosion of the lateral wall of the left
orbit (Figure 1). Magnetic resonance imaging (MRI)
(Figure 2) showed a left lacrimal gland lesion measur­
ing at least 6.4 cm in the maximal antero-posterior
dimension, involving the supero-lateral, supero-
medial and infero-lateral quadrant of the left extra
and intraconal space and preseptal space of the
upper lid. The posterior surface of the globe was
indented without definite invasion. There was also
infiltration of the lateral and superior rectus muscle
with disease extending through the orbital apex intra­
cranially with evidence of disease spread within the
cavernous sinus and destruction of the greater wing of
sphenoid. Further spread of the disease was noted
from the lateral margins of the orbit into the temporal
fossa and invasion of the temporalis muscle over the
craniocaudal distance of 3.5 cm. There was tumour
extension within the inferior orbital fissure into the
pterygopalatine fossa and retrograde spread along the
maxillary division of the trigeminal nerve extending
to the trigeminal ganglion. No definite invasion of the
brain parenchyma was seen. No lymphadenopathy or
brain metastasis was noted.
Lacrimal gland biopsy revealed invasive squa­
mous carcinoma (SCC) (Figure 3a,b). The SCC
showed immunohistochemical positivity for p63
(Figure 3c) and CK5/6 (not shown) and was nega­
tive for markers of lung origin (TTF1 and Napsin
A-not shown). Amongst the malignancy were small
bland glandular structures indicating some back­
ground lacrimal gland acini (Figure 3d top right
inset). There were fragments of stroma that were
highly sclerotic/hyalinised with focal dystrophic cal­
cification (Figure 3e). The sclerotic/hyalinised
stroma showed scattered bland spindle cells (Figure
3f), immunohistochemically positive for calponin,
CK 5/6 and S100 indicative of myoepithelial cells
(Figure 3g). Furthermore, the sclerotic/hyalinised
stroma contained coarse elastin fibres positive for
elastin Von Gieson (EVG) stain (Figure 3h). The
combination of sclerotic/hyalinised stroma, with
coarse elastin, and myoepithelial cells was highly
suspect for a longstanding pleomorphic adenoma.

CONTACT Huzaifa Malick h.malick@nhs.net Ophthalmology Department, University Hospitals of Leicester, Leicester, Leicestershire LE1 5WW, UK
This article has been republished with minor changes. These changes do not impact the academic content of the article.
© 2020 Taylor & Francis Group, LLC
2 H. MALICK ET AL.

Figure 1. (a) Post-contrast fat-supressed axial T1 image demonstrating a large heterogeneously enhancing mass (long arrow) in the
supero-lateral aspect of the left orbit. (b) CT performed following MRI shows subtle erosion of the lateral wall of the left orbit (small
arrow).

Figure 2. MRI (a,b) performed subsequently shows destruction of the lateral wall of the left orbit and extension of tumour into the left
zygomatic space (long arrow).

Thus, the features on balance were judged to be
SCC arising on a background of a sclerotic/hyali­
nised variant of pleomorphic adenoma. The overall
features were those of invasive SCC ex PA.
The patient was discussed in our skull base multidisci­
plinary team meeting (MDT) and it was agreed that this
represented inoperable disease and thus radiotherapy
plus chemotherapy with Cisplatin and 5 Fluorouracil
(5-FU) over 5 consecutive days in 6 cycles was proposed.
The proptosis resolved after two cycles of treatment.
Repeat imaging after three cycles showed a significant
decrease in the lesion size (Figure 4)
Discussion and review of literature
Pleomorphic adenoma represents the most common
epithelial tumour to originate in the lacrimal gland.
Shields et al. found that 78% of all lacrimal gland lesions
were of non-epithelial origin and only 22% were primary
epithelial neoplasms. Of the epithelial neoplasms, the
most common was pleomorphic adenoma (12%).2
These tumours are most commonly benign and slow
growing, mostly involving the orbital lobe of the lacrimal
gland and are principally unilateral. Squamous cell carci­
noma (SCC) ex pleomorphic adenoma represents a very
 ORBIT 3

Figure 3. (a) Haematoxylin and eosin (H&E) stained section showing irregular islands of invasive carcinoma, with eosinophilic
cytoplasm. (b) H&E higher power of the tumour showing invasive squamous carcinoma (SCC) characterised by atypical nuclei (thin
arrow), dyskeratosis (fatter arrows) and ample eosinophilic cytoplasm (asterisk). (c) The SCC is positive for p63 (positive = brown
nuclear stain) by immunohistochemistry. (d) H&E showing very occasional residual lacrimal gland acini (inset top left plate). The
asterisk shows the prominent sclerosed/hyalinised stroma present in some fragments of the biopsy. The smaller arrows show some
invasive SCC. (e) H&E. The sclerotic/hyalinised stroma shows focal dystrophic calcification. (f) H&E. The sclerotic stroma contains bland
spindle cells between the broad collagen fibres. (g). The bland spindle cells in plate F are immunohistochemically positive for Calponin
(main large plate), CK5/6 (bottom left inset) and S100 (bottom right inset). (h) Coarse elastic fibres (black) are seen in the sclerotic/
hyalinised stroma, indicating a sclerotic/hyalinised variant pleomorphic adenoma.

rare transformation of this disease. In this case, the pleo­
morphic adenoma was of the sclerosed/hyalinised type,
well recognised in long-standing lesions.3 This variant
contains very few glands. Pleomorphic adenomas are
fairly unique amongst salivary and lacrimal gland neo­
plasms because they contain elastic fibres, which are
produced by the myoepithelial cells.4 Myoepithelial cells
and elastic tissue were present in the sclerosed/hyalinised
matrix and combined, facilitating the recognition of the
presence of the longstanding PA component.
Primary SCC of the lacrimal gland has been reported in
the literature and has been treated with various treatment
modalities – surgical, radiotherapy and chemotherapy.
Sensory loss and pain are uncommon symptoms of lacrimal
gland PA and, if present, should raise concern for
a malignant lesion such as adenoid cystic carcinoma and
mucoepidermoid carcinoma5,6 Pain was a notable finding
in both our patient and in the case described by Hotta et al.7
However, the other four cases reported in the literature of
SCC of the lacrimal gland are notable for the absence of
4 H. MALICK ET AL.
Figure 4. Post-contrast fat-supressed MRI (a,b) obtained following radiotherapy to the primary site shows reduction in the volume of
the tumour bulk (arrows).
a description of pain possibly suggesting that pain may not
be a suitably precise indicator of malignant disease in
squamous disease of the lacrimal gland.8–11 Despite this,
pain in general warrants immediate investigation and is
generally associated with malignancy until proven other­
wise. Interestingly, palpable lymphadenopathy was also not
described in these cases. Our case showed a good response
to chemotherapy in the form of Cisplatin and 5-FU.
Whether or not squamous carcinoma ex pleomorphic
adenoma requires more careful post excision surveil­
lance remains to be ascertained. Further experience in
the management of this very rare and aggressive tumour
will be invaluable in answering this question.
Disclosure statement
The authors report no conflicts of interest. The authors alone
are responsible for the content and writing of the article.
Funding
No financial support/disclosure for any of the authors above.
This report adhered to the ethical principles outlined in the
Declaration of Helsinki as amended in 2013.
ORCID
10. Su GW, Patipa M, Font RL. Primary squamous cell
Huzaifa Malick http://orcid.org/0000-0001-8365-9756
References
11. Weis E, Rootman J, Joly TJ, Berean KW, Al-Katan HM,
1. Kamei I, Yoshida N, Yukawa S. Malignant transforma­
tion of benign mixed tumor of lacrimal gland to squa­
mous cell carcinoma 19 years after initial surgery: report
of a case. No Shinkei Geka. 1992;20:79–83.
2. Shields CL, Shields JA, Eagle RC, Rathmell JP.
Clinicopathologic review of 142 cases of lacrimal gland
lesions. Ophthalmology. 1989;96(4):431–435. doi:10.1016/
s0161-6420(89)32873-9.
3. Auclair PL, Ellis GL. Atypical features in salivary gland
mixed tumors: their relationship to malignant
transformation. Mod Pathol. 1996;9:652–657.
4. David R, Buchner A. Elastosis in benign and malignant
salivary gland tumors. A histochemical and ultrastruc­
tural study. Cancer. 1980;45(9):2301–2310. doi:10.1002/
1097-0142(19800501)45:9<2301::aid-cncr2820450913>
3.0.co;2-#.
5. Chandrasekhar J, Farr DR, Whear NM. Pleomorphic
adenoma of the lacrimal gland: case report. Br J Oral
Maxillofac Surg. 2001;39(5):390–393. doi:10.1054/
bjom.2001.0624.
6. Harrison W, Pittman P, Cummings T. Pleomorphic
adenoma of the lacrimal gland: A review with updates
on malignant transformation and molecular genetics.
Saudi J Ophthalmol. 2018;32(1):13–16. doi:10.1016/j.
sjopt.2018.02.014.
7. Hotta K, Arisawa T, Mito H, Narita M. Primary squamous
cell carcinoma of the lacrimal gland. Clin Exp Ophthalmol.
2005;33(5):534–536. doi:10.1111/j.1442-9071.2005.01043.x.
8. Wright JE, Rose GE, Garner A. Primary malignant
neoplasms of the lacrimal gland. Br J Ophthalmol.
1992;76(7):401–407. doi:10.1136/bjo.76.7.401.
9. Fenton S, Srinivasan S, Harnett A, Brown I, Roberts F,
Kemp E, et al. Primary squamous cell carcinoma of the
lacrimal gland. Eye. 2003;17:424–5. 2. doi:10.1038/sj.
eye.6700323.
carcinoma arising from an epithelium-lined cyst of the
lacrimal gland. Ophthal Plast Reconstr Surg. 2005;21
(5):383–385. doi:10.1097/01.iop.0000176263.07921.22.
Pasternak S, et al. Epithelial lacrimal gland tumors:
pathologic classification and current understanding.
Arch Ophthalmol. 2009;127(8):1016–1028. doi:10.1001/
archophthalmol.2009.209.