Adenoid cystic carcinoma of base of tongue: Rare tumor in rare location treated with upfront curative radiotherapy

Abstract

Adenoid cystic carcinoma (ACC) is a rare variant of adenocarcinoma accounting for <1% of all head and neck malignancies. They arise mostly from minor salivary glands of the upper aero‑digestive tract and are treated mainly by surgical resection. Hard palate is the most
common site while base of tongue (BOT) locations are extremely rare. We hereby report a case of ACC of BOT in a 65‑year‑old male who presented with dysphagia of 8 months duration. The patient was deemed a nonsurgical candidate due to the location of the tumor and morbidity of surgery. We treated him with radiotherapy (RT) after a thorough histological diagnosis. The patient responded well to RT with complete remission of the tumor and significant symptomatic relief. He has been started on oral imatinib mesylate in view of CD‑117 positivity. At present, on regular follow‑up for over a year without any evidence of local recurrence or distant metastasis

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Introduction
Adenoid cystic carcinoma (ACC) originates
mainly from salivary glands distributed
throughout the head and neck region. Minor
salivary glands of the hard palate give rise
to 60% cases of ACCs while the base of
tongue (BOT) lesions are extremely rare
constituting a miniscule amount.[1] The aim of
reporting our case is to sensitize the medical
fraternity that though surgery has been
traditionally considered the proven standard
of care for head and neck or BOT ACC,
conformal radiotherapy (RT) can act as a
denitive therapeutic modality with excellent
clinical and radiological response.[2] However,
concurrent chemo‑RT have a limited role.[3]
Case Report
A 65‑year‑old male with no known
comorbidities presented with complaints
of dysphagia of 8 months duration. He
was a tobacco smoker since last 40 years
without any history of alcohol intake. His
hematological and biochemical profiles
were normal. Hopkins telescopy showed an
ulceroproliferative growth right BOT slightly
crossing midline [Figure 1]. No neck nodes
were palpable. Contrast enhanced computed
tomography (CT) scan face and neck
showed a poorly dened heterogeneously
enhancing 4.1 cm × 3.6 cm mass lesion
epicentered in the right BOT extending
posteriorly just short of vallecula [Figure 2]
without any cervical lymphadenopathy.
Biopsy from the lesion showed cribriform
pattern of tissue with tumor cells forming
ducts, nests, and tubules with pockets
of mucin suggestive of ACC [Figure 3].
Immunohistochemistry (IHC) stained
positive for CD‑117 [Figure 4] and
pan‑cytokeratin (pan‑ck) while negative
Date of Submission: 03‑08‑2016
Date of Acceptance: 12‑10‑2016
Address for correspondence:
Dr. Abhishek Purkayastha,
Department of Radiation Oncology,
Army Hospital, Research and
Referral, Dhaula Kuan, Delhi Cantt,
New Delhi ‑ 110 010, India.
E‑mail: abhi5296@gmail.com
Case Report
ABSTRACT
Adenoid cystic carcinoma (ACC) is a rare variant of adenocarcinoma accounting for <1% of
all head and neck malignancies. They arise mostly from minor salivary glands of the upper
aero‑digestive tract and are treated mainly by surgical resection. Hard palate is the most
common site while base of tongue (BOT) locations are extremely rare. We hereby report a case
of ACC of BOT in a 65‑year‑old male who presented with dysphagia of 8 months duration. The
patient was deemed a nonsurgical candidate due to the location of the tumor and morbidity
of surgery. We treated him with radiotherapy (RT) after a thorough histological diagnosis. The
patient responded well to RT with complete remission of the tumor and significant symptomatic
relief. He has been started on oral imatinib mesylate in view of CD‑117 positivity. At present, on
regular follow‑up for over a year without any evidence of local recurrence or distant metastasis.
Adenoid cystic carcinoma of base of
tongue: Rare tumor in rare location
treated with upfront curative
radiotherapy
Abhishek Purkayastha, Neelam Sharma, Rajeev Chugh1, Abhishek Dwivedi2
Departments of Radiation Oncology, 1ENT and 2Radiology, Army Hospital Research and Referral,
New Delhi, India
Key words: Adenoid cystic carcinoma, base of tongue, radiotherapy
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DOI:
10.4103/0976‑6944.194377
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Purkayastha, et al.: Adenoid cystic carcinoma of base of tongue
Indian Journal of Oral Sciences  Vol. ??  Issue ?  ???
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for p63, desmin, vimentin, melan A, CD‑20, CD‑99,
chromogranin and synaptophysin, conrming the diagnosis
of ACC. Metastatic workup with positron emission
tomography (PET) scan was negative.
In view of the old age of patient, location of the tumor
requiring morbid resection resulting in long‑term
sequelae, denitive surgery was not contemplated. We
treated him with upfront RT by 3‑dimensional conformal
RT (3‑DCRT) technique to face and neck with photons
to a dose of 66 Gray (Gy) in 33 fractions. He tolerated
treatment well with signicant improvement in dysphagia.
Response assessment with Hopkin’s telescopy [Figure 5]
and CT scan face and neck 12 weeks post therapy showed
a complete response (CR) to RT [Figure 6]. To maintain
the CR status of the patient, he was started on oral imatinib
mesylate (400 mg/day). At present, on regular follow‑up
for over a year without any evidence of local recurrence
or distant metastasis.
Discussion
ACC is a rare, slow‑growing neoplasm of major and
minor salivary glands accounting for <1% of all head and
neck tumors and 10% of all salivary gland tumors.[4] They
originate from secretory glands found predominantly in
regions such as lips, oral cavity, oropharynx, larynx, external
auditory canal, nose and upper aero‑digestive tract locations
such as esophagus and trachea. ACC of salivary glands was
rst described by Robin, Lorain, and Laboulbene in 1853
as a cylindroma and was renamed as ACC in 1930.[5] Spiro
et al. in 1974 studied 242 cases salivary gland ACC and
described hard palate as the most common site followed by
oral tongue with very few in BOT.[1] ACC is characterized
by perineural invasion (PNI), high rates of loco‑regional
Figure 1: Hopkin’s telescopic view of patient on presentation
showing an ulceroproliferative growth right base of tongue
(black pointer)
Figure 2: Computed tomography scan face and neck axial image
showing a poorly defined heterogeneously enhancing mass lesion
right base of tongue extending posteriorly just short of vallecula
(yellow pointer)
Figure 3: Biopsy from the lesion showed cribriform pattern of tissue
with tumor cells forming ducts, nests, and tubules with pockets of
mucin suggestive of adenoid cystic carcinoma (H and E, ×10)
Figure 4: Immunohistochemistry showing CD-117 positivity (×100)
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Purkayastha, et al.: Adenoid cystic carcinoma of base of tongue
Indian Journal of Oral Sciences  Vol. ??  Issue ?  ??? 3
recurrence and tendency for an indolent but asymptomatic
metastasis to lung followed by liver.
Clinical diagnosis of ACC BOT is difcult as it may be
confused with other malignant lesions arising at the same
site like squamous cell carcinoma (SqCC), lymphoma,
clear cell carcinoma, ectopic thyroid tissue, melanoma,
or even a metastatic lesion. Familiarity with these lesions
and how they differ from other lesions of oral cavity
and oropharynx can signicantly aid in their diagnosis
and treatment. ACC BOT generally present as a painless
submucosal growth in contrast to a SqCC presenting with
dysphagia or odynophagia, though our case presented
with dysphagia. They are generally locally advanced at
presentation with 75% cases being T3/T4 on diagnosis.[2]
This can be explained by the fact that the clinical course
is usually asymptomatic with patients presenting late
to medical professionals. The average time from initial
occurrence to clinical manifestation has been postulated
to be from 6 months to 8 years.[6] Cervical lymph nodal
involvement in oropharyngeal ACC ranges from 2% to
43% and may not be a presenting symptom in contrast to
an oropharyngeal SqCC which typically presents with a
neck swelling.[7] Regarding etiology of ACC, there are no
established risk factors as in SqCC such as tobacco smoking,
alcohol consumption, or human papillomavirus infection.
However, chromosomal translocation t(6;14) (q25; q13) has
been postulated as a critical event along with expression of
CD‑117 or c‑Kit in the development of ACC BOT.[8] No
sex predilection has been documented so far.
ACC of oral cavity and oropharynx is characterized by a
slow, indolent and meandering clinical course with high
rates of local recurrence despite extensive surgery due to
local inltration and PNI. Late but largely asymptomatic
metastasis distinguishes them from SqCC of same sites.
ACC metastasize mainly to lung followed by liver, brain,
bone, thyroid, spleen, and even pancreas.[9] Imaging with
chest X‑ray, CT scans, magnetic resonance imaging generally
does not possess the specic features to differentiate the
mass from other BOT malignancies while PET scans
and bone scans often form the part of a metastatic
workup. Tubular (Grade I), cribriform (Grade II), and
solid (Grade III) are the three histological patterns of ACC
with tubular having the best prognosis and solid having the
worst. However, few authors have described the stage of
the disease and not histology, as the relevant prognostic
factor.[1] The diagnosis depends on the microscopic
morphological pattern of myoepithelial and ductal cells
while IHC plays a limited role apart from the expression
of CD‑117 or c‑Kit.[2] Due to its location, IHC helps in
differentiating and excluding other differential pathologies
such as low‑grade adenocarcinoma, pleomorphic adenoma,
lymphomas, melanomas, soft tissue sarcoma, or a metastatic
lesion from any primary.
Regarding the management aspect of ACC BOT, surgery
has been traditionally considered the primary therapeutic
modality. The main aim of surgery is to obtain a negative
surgical margin allowing successful loco‑regional control
and long‑term survival.[10] ACC shows submucosal growth
and PNI making complete surgical resection challenging.
Wide local excision and free tissue transfer like radial
forearm free ap reconstruction has been used by few
institutes. Novel surgical techniques like trans‑oral laser
excision, trans‑oral robotic surgery, and ultrasound‑guided
interstitial photodynamic therapy have been used with
satisfactory results.[11,12] However, aggressive resection like
total glossectomy of BOT lesions may result in signicant
iatrogenic morbidity affecting speech and swallowing
functions due to close proximity to the laryngeal apparatus,
thus affecting the quality of life of these patients. Therefore,
Figure 5: Post-radiotherapy Hopkin’s telescopic view showing
clinical complete response to therapy
Figure 6: Post-radiotherapy computed tomography scan axial image
showing no evidence of any disease
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Purkayastha, et al.: Adenoid cystic carcinoma of base of tongue
Indian Journal of Oral Sciences  Vol. ??  Issue ?  ???
4
it depends on the treating surgeon to whether opt for a
radical or a conservative surgical approach depending on
the stage of tumor, histology and general condition of
the patient.
RT has generally been used as an adjuvant therapeutic
policy after surgery in most cases of head and neck ACC.
Close or positive surgical margins, residual disease, skull
base invasion, and PNI are the known indications for RT to
decrease local recurrence and improve survival. However,
the use of RT as a denitive or upfront treatment modality
has not been explored by large randomized control trials,
maybe due to the rarity of this disease. Few case series
have used RT alone for unresectable head and neck
ACC.[13] Conformal RT techniques like 3‑DCRT, intensity
modulated radiation therapy and image‑guided radiation
therapy have replaced the traditional 2‑dimensional RT
planning, allowing curative higher tissue dosage and less
normal tissue toxicity. Carbon ion RT and brachytherapy
have been used to treat local recurrences by few institutions.
There are no denite RT dosage guidelines for ACC BOT
though most authors have used 45–60 Gy in a postoperative
setting. Since our patient was deemed unresectable, we
used denitive RT by 3‑DCRT technique to deliver a
conventional fractionation dose of 66 Gy in 33 fractions
to which the patient showed a CR. Although the risk of
occult LN metastasis is low, it is advised to electively treat
the neck for lymphatic‑rich primary in BOT and the base of
skull for PNI.[7,13] Concurrent chemo‑RT with carboplatin
and paclitaxel has been used without any signicant clinical
benet but with more toxicity.[3] Imatinib mesylate, a c‑Kit
tyrosine kinase inhibitor has been tried against ACC of
salivary glands.[14] Since our patient was positive for CD‑117
or c‑Kit, we used oral imatinib to maintain the CR status.
ACC is an uncommon salivary gland malignancy that
manifests with a spectrum of histopathological patterns
and follows a progressive clinical course. Attempts
to understand the development and progression of
these tumors have been non‑benecial due to the lack
of malignant precursors and the absence of animal
studies. Further, identication of unique chromosomal
abnormalities, biologic pathways is necessary for the
sequencing of events associated with its evolution and
the development of novel biological targets for therapy.
By reporting this case, we recommend that the diagnosis
of ACC BOT should always be considered in patients
presenting with a BOT lesion so as to enable a prompt
initiation of appropriate treatment. We also emphasize the
fact that RT can be used in all cases of ACC BOT lesions
with a signicant clinical benet without the morbidity of
extensive surgery.
Acknowledgments
We thank the patient for allowing us to publish the case
report and use the images taken during his stay in hospital.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conicts of interest.
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