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Novel Insights from Clinical Practice
Received: February 7, 2017
Accepted after revision: February 20, 2017
Published online: May 11, 2017
Acta Cytologica 2017;61:237–241
DOI: 10.1159/000464271
Adenoid Cystic Carcinoma of the
Larynx Presenting as a Thyroid Mass and
Brief Literature Review
Sadegh Shirian a, c Maryam Maghbool b Azita Aledavood c
Shahrzad Negahban c Bijan Khademi d, e Yahya Daneshbod c
a
Department of Pathology, School of Veterinary Medicine, Shahrekord University, Shahrekord, b Department of
Pathology, Fasa University of Medical Sciences, Fasa, and c Dr. Daneshbod Pathology Laboratory, Shiraz Molecular
Pathology Research Center, and d Department of Otolaryngology and e Otolaryngology Research Center,
Shiraz University of Medical Sciences, Shiraz, Iran
Established Facts
• Adenoid cystic carcinoma is the most common malignant tumor in the major and minor salivary
glands. It can originate from minor salivary glands of the larynx and present as thyroid nodule by direct tumor invasion or as metastasis.
• Adenoid cystic carcinoma of the larynx and trachea is very rare.
Novel Insights
• Cytopathological, immunohistochemical, radiographic, and ultrasonographic features of the larynx
presenting as a thyroid mass is very rarely reported.
Abstract
Background: Adenoid cystic carcinoma (ACC) of the larynx
and trachea is very rare. Case: A 45-year-old man with ACC
of the larynx presenting as a thyroid mass is reported in this
study. Physical examination revealed a large solid thyroid
nodule in the left lobe without any lymphadenopathy. A
technetium thyroid scan showed multinodular goiter with
© 2017 S. Karger AG, Basel
E-Mail karger@karger.com
www.karger.com/acy
cold nodules in the left lobe, isthmus, and functioning nodules in the right lobe. A large thyroid mass originating from
the left side of the larynx, mostly the left vocal cord and the
infraglottic part, was seen using enhanced magnetic resonance imaging after rupture of the thyroid cartilage on the
left side. Ultrasound-guided fine needle aspiration smears
and cell blocks of the thyroid nodule showed highly cellular
smears composed of large tissue fragments, three-dimensional clusters, and sheets of neoplastic cells with slightly en-
Correspondence to: Dr. Maryam Maghbool
Department of Pathology, Fasa University of Medical Sciences
Fasa 71345-1734 (Iran)
E-Mail maghbol.maryam @ yahoo.com
Dr. Yahya Daneshbod
Dr. Daneshbod Pathology Laboratory
Shiraz Molecular Pathology Research Center
Shiraz (Iran)
E-Mail daneshbk @ yahoo.com
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Keywords
Adenoid cystic carcinoma · Thyroid · Larynx · Fine needle
aspiration · Cytopathology
© 2017 S. Karger AG, Basel
Introduction
Thyroid nodules are common, and the accuracy of
prevalence estimates is largely dependent on the method
applied for their identification [1]. The estimated prevalence of thyroid nodules ranges from 4 to 7% using palpation alone [2]; however, it increases to 20–76% in the
adult population using ultrasound (US) examination [3].
About 95% of nodules are benign, and only 5% of them
are diagnosed as malignant [1]. The most common thyroid tumors are papillary and follicular carcinomas. Metastatic tumors in the thyroid gland are uncommon but
well established. About 1.4–3% of all thyroid malignancies become metastatic. The most common thyroid metastases are from renal cell carcinoma, [4] breast carcinoma, endocervical adenocarcinoma, and lung carcinoma. Adenoid cystic carcinoma (ACC) is the most common
malignant tumor in the major and minor salivary glands.
It can originate from minor salivary glands of the larynx
and present as thyroid nodule by direct extension or in
metastatic form [1]. In our patient, a thyroid mass was
suspected based on the initial clinical and US manifestations; therefore, US-guided fine needle aspiration (FNA),
total laryngectomy, and thyroidectomy were performed.
Pathological, immunohistochemical, radiographic, and
US features of ACC in this context are presented. The literature on ACC is also reviewed.
Case Report
A 45-year-old man presented with mild hoarseness and a
3-month history of a left-sided neck mass. No history of dyspnea,
fever, dysphagia, and neck pain or weight loss were identified.
Physical examination revealed a large solid thyroid nodule in
the left lobe without any lymphadenopathy. US illustrated enlargement of the left thyroid lobe with multiple nodularity. A technetium thyroid scan showed multinodular goiter with cold nodules
in the left lobe, isthmus, and functioning nodules in the right lobe
(Fig. 1a). A large thyroid mass originating from the left side of the
larynx, mostly the left vocal cord and the infraglottic part, was seen
after rupture of the thyroid cartilage on the left side using en-
238
Acta Cytologica 2017;61:237–241
DOI: 10.1159/000464271
hanced magnetic resonance imaging (Fig. 1b). The airways were
narrow with a marked midline shift. The carotid sheath showed
lateral deviation because of a pressure effect. Chest X-ray and direct laryngoscopy results were normal. The mass was in direct contact with the esophagus. US-FNA smears and cell blocks of the
thyroid nodule showed highly cellular smears composed of large
tissue fragments, three-dimensional clusters, and sheets of neoplastic cells with slightly enlarged round and hyperchromatic nuclei, scanty blue cytoplasm surrounded with variably sized pinkto-purple (Wright stain) mucoid-like matrix and many isolated
naked neoplastic cells as well as red blood cells (Fig. 1c). A cell
block specimen showed the cribriform pattern of ACC (Fig. 1d).
Immunohistochemically, cell blocks were positive for C-kit and
CK 7 on the cribriform growth pattern of the tumoral cells (Fig. 2a,
b). However, protein expression of thyroglobulin and thyroid
transcription factor (TTF-1) was not detectable (Fig. 2a). The patient underwent total laryngectomy and thyroidectomy, and laryngeal submucosal adenoid cystic carcinoma with thyroid invasion
was confirmed (Fig. 2c). Histological evaluation showed ACC invading the thyroid gland (Fig. 2d).
Discussion
The primary aim of this study was to describe a patient
with ACC of the larynx presenting as a thyroid mass. Although ACC is not an uncommon tumor in the salivary
glands, its occurrence in the larynx and trachea is very
rare [1]. Evaluation of cytology specimens in thyroid
nodules is based on three major criteria; cellularity/colloid ratio, smear pattern, and cytomorphological features
[5]. If the cytological findings do not determine the definite origin of the thyroid mass, the possibility of direct
tumor invasion or metastasis must be considered. FNAs
of ACC are usually cellular smears with a monomorphic
population of basaloid cells in tight clusters with scant
cytoplasm, high nuclear/cytoplasmic ratio, coarse chromatin, small nucleoli, and indistinct cell borders. Acellular hyaline stroma in globular or cylindromatous formation is present in cribriform and tubular subtypes and
mimicking ropy colloid or amyloid materials; therefore,
it can lead to the misdiagnosis of papillary or medullary
carcinoma of the thyroid [2]. Other differential diagnoses
that should be considered are pleomorphic adenoma,
basal cell adenoma, epithelial-myoepithelial and polymorphous low-grade carcinomas, and skin appendage
tumors. In cytologic smears of thyroid nodules, ACC
must be differentiated from thyroid neoplasms such as
follicular, medullary, papillary, and anaplastic carcinomas [6, 7].
In difficult situations, immunocytochemistry can be
applied on cytology specimens to distinguish primary
thyroid neoplasms from secondary tumors. ThyroglobuShirian/Maghbool/Aledavood/Negahban/
Khademi/Daneshbod
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larged round and hyperchromatic nuclei. Immunohistochemical study showed that the cell block expressed C-kit
and CK 7 on the cribriform growth pattern of the tumoral
cells. However, protein expression of thyroglobulin and thyroid transcription factor-1 was not detectable. Conclusion:
To approach a thyroid nodule, direct invasion or metastatic
tumors of other organs must be borne in mind.
the cribriform growth pattern of the tumoral cells. a Negative immunoreactivity
of tumoral cells for TTF-1 and positive in
background thyroid cells (double arrowhead). Inset: positivity for C-kit and CK 7.
c Gross pathological specimen of total laryngectomy and thyroidectomy. Arrowheads show site of laryngeal perforation.
d Adenoid cystic carcinoma invading the
thyroid gland. HE. ×200.
d
a
b
c
d
Color version available online
c
lin, calcitonin, and TTF-1 are markers which stain positive in primary thyroid neoplasms. Myoepithelial markers, such as muscle-specific actin and S-100, are positive
in ACC [6].
To date, 9 cases of laryngeal ACC with thyroid invasion have been reported (Table 1) [4, 5, 8–12]. Thyroid
nodules are common findings, and about 97% of them are
primary (benign or malignant). Only 1.4–3% of all thyroid malignancies are metastatic tumors. The most common metastatic tumors are renal cell carcinomas, breast
carcinomas, endocervical adenocarcinomas, and lung
carcinomas [5]. Adjacent neoplasms directly invade the
Adenoid Cystic Carcinoma of the Larynx
Acta Cytologica 2017;61:237–241
DOI: 10.1159/000464271
239
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Fig. 2. Cell blocks show scattered positivity
for CK 7 (a, arrow head) and C-kit (b) on
b
Color version available online
Fig. 1. a Thyroid scan shows a cold nodule
in the left thyroid lobe. b Enhanced MRI of
the neck shows a large thyroid mass in the
left side. c Fine needle aspiration cytology
of the thyroid nodule shows a monomorphic population of basaloid cells in tight
clusters with scant cytoplasm, high nuclear/cytoplasmic ratios, coarse chromatin,
small nucleoli, and indistinct cell borders
in cellular smears. Wright stain. ×200.
d Cell block specimen showing a cribriform pattern of adenoid cystic carcinoma.
HE. ×200.
a
Table 1. Review of the literature on laryngeal adenoid cystic carcinoma with thyroid invasion
First
author
Year
Sex
Age,
years
Site
Treatment
Kashiwagi [8]
2016
F
33
Immediately below the vocal cords
Total laryngectomy with elective
bilateral neck dissection
Yang [9]
2005
M
NA
Trachea
Thyroidectomy, laryngotracheal
resection, radiotherapy
Natarajan [10]
2004
M
76
Submucosal glands of the pyriform
sinus and adjacent larynx
No treatment due to arrest
Idowu [5]
2004
F
60
Larynx, left vocal cord, and trachea
Total laryngectomy and
thyroidectomy with radiotherapy
Hogg [11]
1999
F
72
Deep into the left cricopharyngeus
muscle
Total laryngectomy
Na [12]
1995
M
33
Trachea
Total laryngectomy and total
thyroidectomy
F
35
Trachea
Total thyroidectomy (1st) and
tracheal resection (2nd)
45
Trachea
Total laryngectomy and right
thyroidectomy
38
Trachea
Tracheal resection and partial
thyroidectomy
66
Beneath the mucosa of the upper
trachea
Upper 5 tracheal ring excision and
thyroidectomy
1984
F
thyroid gland. The most common forms of direct thyroid
invasion are epithelial malignant tracheolaryngeal neoplasms of squamous origin [13]. Nonsquamous carcinomas are very rare (<1%), and ACC is the most prevalent
form [14].
ACCs are rare and account for <1% of malignant laryngeal tumors. They mostly arise from subepithelial minor salivary glands of the subglottic area and present as
submucosal masses [4, 5]. They are slow-growing malignant tumors which spread by direct extension, perineural
invasion, and hematogenous metastasis. Lymphatic invasion is rare in ACC cases. Direct spread of a thyroid malignancy to the trachea is a rare phenomenon; moreover,
the reverse situation is extremely rare [15].
In conclusion, to approach a thyroid nodule, direct tumor invasion or metastasis to other organs must also be
considered. To obtain an accurate medical history, clinical and radiographic examinations are essential for the
evaluation of thyroid nodules, but not useful for choosing
the suitable treatment approaches, which largely depend
on immunohistochemical, pathological, and US-FNA cytopathological findings.
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Acta Cytologica 2017;61:237–241
DOI: 10.1159/000464271
Acknowledgments
The authors would like to thank the Shiraz Molecular Pathology Research Center and Shahrekord University and Ms. H.
Shojaeefard for her technical help.
Statement of Ethics
The institutional review board of the Dr. Daneshbod Laboratory approved the study. The author group obtained written informed consent from the patient.
Disclosure Statement
The authors have no conflicts of interest to declare.
Shirian/Maghbool/Aledavood/Negahban/
Khademi/Daneshbod
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Zirkin [4]
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Adenoid Cystic Carcinoma of the Larynx
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