Abstract
Polymorphous low-grade adenocarcinoma (PLGA) is a rare entity scarcely
reported in major salivary glands, with minimal incidences in the Asian
population. It generally presents as a solid tumor with morphological
diversity and variable histological patterns. This article reports PLGA
of the parotid gland, mimicking a cystic lesion in an Indian male, with
a review of relevant literature. A 64-year-old male patient presented
with a slow-growing swelling of the left parotid region for the last 10
years. The cytology report suggested a cystic swelling. The patient
underwent a superficial parotidectomy. A detailed histopathological
examination confirmed it as PLGA. The patient remains disease over 24
months of post-surgery follow-up.
Key Clinical Message: PLGA is a rare malignancy arising de novo
or ex-PMA from salivary glands’ terminal (intercalated) duct cells. The
recommended treatment of PLGA, independent of its location, consists of
the wide local surgical excision, and neck dissection should be added
only in cases with cervical lymphadenopathy.
Keywords: Lymphoepithelial cyst, Parotid gland, Pleomorphic
adenoma, Polymorphous adenocarcinoma, Polymorphous Low-Grade
adenocarcinoma, Salivary gland tumor.
INTRODUCTION
Polymorphous low-grade adenocarcinoma (PLGA) is a rare malignant
epithelial tumor of salivary glands and was first described as a
distinct clinicopathological entity-”Lobular carcinoma”, by Freedman and
Lumerman in 1983.1 Evans and Batsakis suggested the
term polymorphous low-grade adenocarcinoma for the tumor in
1984.2 Due to its polymorphous histology and indolent
clinical behavior, the WHO also adopted the term in its second
classification of histological typing of salivary gland tumors in
1991.3 The WHO classification of salivary gland tumors
(2018) categorized the indolent PLGA as a classical variant of
Polymorphous adenocarcinoma (PAC), being defined as ”a malignant
epithelial tumor characterized by cytological uniformity, morphological
diversity, an infiltrative growth pattern, and low metastatic
potential”.4
PLGA has been reported in the 3rd to
7th decade of life, with over 90% of cases occurring
above 40 years, with a mean age of 61.3 years at
diagnosis.5 This tumor has a clear female predilection
in a ratio of 2.15:1.6 Although rare, it is the second
most common malignancy of the minor salivary glands (MiSG) located
frequently in the posterior hard and soft palate (60% of cases, range:
49%−87%). The incidences of occurrence in the labial and buccal
mucosa, retromolartrigone, tongue, floor of the mouth, nasal cavity,
paranasal sinuses, larynx, trachea, and bronchi have also been
reported.5-7 It may occasionally originate in major
salivary glands, particularly the parotid, in 3% (0% to 9%)
case.5,7 The tumor also shows racial preponderance,
with 75 % of cases reported in whites and less than 2 % (0.5%-1.6%)
in Asians.6,7 As per the author’s literary search, a
total of nine cases of PLGA in the parotid gland have been reported by
Asian authors till 01/06/2023 (Table 1). Only three cases (Case
No.1,3,5) have been reported from India to date.The present case
describes the rare occurrence of PLGA presenting with a unique cystic
appearance, the first of its kind, in the parotid gland of an Indian
male.
CASE HISTORY/EXAMINATION
A 64-year male patient reported having complained of left cheek swelling
for the last 10 years. History revealed that it started as a small
painless nodule that progressed slowly over time without any associated
symptoms, such as dysphasia, dysphonia, dysphagia, odynophagia, otalgia,
or odontophagia. He had visited several regional professionals for the
same and was prescribed antibiotics for the aural and dental infections.
The drainage through a local incision was also attempted three years
back without significant results. No record of previous intervention was
available with him.
Clinical examination recorded a swelling of 4×4 cm size in the left
preauricular region with extension to the infra-auricular area (Fig.
1a).It was non-tender, non-fluctuant, localized, firm in consistency,
and had well-defined margins without any fixation to the underlying
structures on palpation. There was an absence of cervical
lymphadenopathy, and the facial nerve functions were maintained without
any evidence of weakness. The detailed head and neck examination
identified no other significant etiological factor. The hematological
and biochemical liver and renal function tests were within normal range.
The viral markers were negative for HIV and Hepatitis B infection. Fine
needle aspiration cytology using a 26 gauge needle suggested a cystic
lesion (Fig. 1b). A rapid filling of the swelling immediately after the
pathologist also reported FNAC. Pre-operative contrast-enhanced computed
tomography (CECT) recorded a well-defined cystic mass of 43×41×39 mm in
the left parotid with peripheral enhancement and extension into the deep
lobe (Fig. 1c and 1d). A provisional diagnosis of a benign
lymphoepithelial cyst or Warthin’s tumor was suggested.
METHODS
Based on thefindings above, the case was planned for superficial
parotidectomy with preservation of the facial nerve under general
anesthesia, and written informed consent was taken. The site was
approached through a modified Blair incision (Fig. 2a),and a single 5cm
x6cm soft tissue mass was obtained (Fig. 2b).
The specimen was sent for a detailed histopathological examination. The
postoperative flap necrosis was observed on day 5 (Fig. 3a)and managed
conservatively. Sutures were removed on the 10th day,
and the patient was discharged on the 25th day without
any postoperative complications (Fig. 3b).
The histopathology reported that a 5x4x3cm mass exhibited a hemorrhagic,
fluid-filled cut section macroscopically. Microscopically, an
infiltrative pattern at the periphery was evident (Fig. 4a). The cells
were arranged in various architectural patterns, including tubular,
trabecular, solid, and cribriform (Fig. 4b and 4c). The small to
medium-sized round tumor cells had a uniform shape, an indistinct
border, and eosinophiliccytoplasm (Fig. 4d and 4e). Their nuclei were
round to ovoid that contained open vesicular nuclear chromatin and
inconspicuous nucleoli (Fig. 4d and 4e). Considering the histological
features, the final diagnosis of PLGA was made. It was further confirmed
by the positivity of S-100 on immunohistochemistry (Fig. 4f). The
patient was informed about the diagnosis and potential complications and
referred to a higher center for postoperative radiotherapy. However it
was rigidly refused by himdue to anticipated complications. His
postoperative CT recorded the signs of chronic parotitis without any
evidence of residual disease. The patient was recalled monthly for the
first 3 months, followed by every three months at the present institute.
The patient was asymptomatic without evidence of recurrence, metastasis,
or associated complications at the final follow-up of 24 months. The
scheduled follow-ups are expected to be carried out in the future to
assess the treatment’s long-term outcome.
DISCUSSION
PLGA is a rare malignancy arising de novo or ex-PMA from salivary
glands’ terminal (intercalated) duct cells.6 It
generally presents as an oval, firm to solid, circumscribed,
slow-growing swelling with variable histological
pattern.5,6 The FNAC is recommended to be the
first-line tissue-based testing procedure for establishing the
pre-surgical diagnosis for major salivary gland
PGLA.5,8 However, the procedure is challenging because
of limited tissue access and variable cytoarchitectural
findings.8 The cytological smears of PLGA are
hypercellular with branched papillary clusters and sheets of uniform
cells with moderately eosinophilic cytoplasm; round-to-oval nucleus with
bland or absent nucleoli; finely stippled chromatin; and abundant
hyaline globules within the matrix.8 Contrarily, these
findings were completely absent in the present case, and the smear
suggested a cystic lesion. Due to the absence of any specific
radiographic features, the role of imaging for PLGA is also limited to
assessing its origin, local extent, and any regional or distant
metastasis rather than distinguishing a distinct diagnosis. The PLGAs of
parotid gland had mostly been provisionally misdiagnosed as pleomorphic
adenomas, adenoid cystic carcinoma, epidermal tumor, chronic parotitis,
and multicystic lesion, etc., in the literature (Table 1), thereby
revealing the lack of specificity of the pre-operative diagnostic
testing for them.