Anatomic Pathology / ADENOID CYSTIC CARCINOMA
Adenoid Cystic Carcinoma
A Pitfall in Aspiration Cytology of the Thyroid
Michael O. Idowu, MD,1 Evan R. Reiter, MD,2 and Celeste N. Powers, MD1
Key Words: Adenoid cystic carcinoma; Hyaline globules; Thyroid neoplasms
DOI: 10.1309/NKED4TJXUENR21M2
Abstract
While adenoid cystic carcinoma is not an uncommon
tumor in the salivary glands, its occurrence in the larynx
and trachea is rare. Extension of an adenoid cystic
carcinoma of the larynx and trachea to the thyroid with
manifestation as a thyroid nodule is extremely rare.
However, this possibility always should be considered
whenever there are cytologic features suggestive of
adenoid cystic carcinoma in thyroid aspirates and
when there is a history of adenoid cystic carcinoma in
the trachea or larynx or in any part of the body.
Direct invasion of the trachea by aggressive tumors originating in the thyroid gland is an unusual but well-documented
phenomenon.1-3 The reverse situation, that is, a primary
tracheal neoplasm invading by direct extension into the
thyroid gland and manifesting as a thyroid mass is even less
common.1 We present 2 cases of adenoid cystic carcinoma
arising in the laryngotracheal complex and involving the
thyroid gland by direct extension. In both cases, the initial
clinical manifestation was a suspected thyroid mass for which
fine-needle aspiration (FNA) was performed. The cytomorphologic features of adenoid cystic carcinoma in this context
are presented, and the potential confusion of adenoid cystic
carcinoma with thyroid neoplasms is discussed.
Case 1
A 68-year-old woman sought care because of a 6-month
history of increasing dyspnea without hoarseness. She had no
relevant medical history and denied the use of tobacco and
alcohol. The physical examination revealed upper airway breath
sounds with stridor. A solitary palpable mass was identified in
the thyroid. An FNA was performed, and a diagnosis of papillary carcinoma was made ❚Image 1❚ and ❚Image 2❚. A subsequent computed tomography (CT) scan of the neck revealed a
large, left-sided thyroid mass that extended to and completely
encircled the trachea causing narrowing of the airway. Total
thyroidectomy and laryngectomy were performed, and the
tumor was excised completely. The histologic examination
revealed adenoid cystic carcinoma arising in the trachea ❚Image
3❚, infiltrating the tracheal rings and extending through the
trachea anteriorly into the posterior portion of the left lobe of the
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❚Image 1❚ (Case 1) Papillary carcinoma was the initial
diagnosis. Fine-needle aspiration. Low-power aspiration
cytology showing “ropy colloid” and a monomorphic
population of basaloid cells (rapid Romanowsky, ×50).
❚Image 2❚ (Case 1) Papillary carcinoma was the initial
diagnosis. Fine-needle aspiration. Medium power aspiration
cytology showing vague microfollicle-like structure, round to
oval cells with fine granular chromatin, and indistinct nucleoli
(rapid Romanowsky, ×100).
Case 2
❚Image 3❚ (Case 1) Adenoid cystic carcinoma. Surgical
specimen (thyroidectomy and laryngectomy). Low-power
histologic stain of resected specimen showing characteristic
cribriform pattern (H&E, ×50).
thyroid. The patient completed a 4-week course of postoperative
radiotherapy with a total dose of 50 Gy. Six months postoperatively, she had no dyspnea, was breathing via her tracheostomy,
and denied dysphagia. Examination showed no cervical masses
or lymphadenopathy. However, shortly after this follow-up visit,
she sustained a fall that resulted in a subdural hematoma. Her
condition progressively worsened and she died a few days after
the head injury. No autopsy was performed.
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A 60-year-old man with hypertension, hepatitis C, and
previous abuse of intravenous drugs, tobacco, and alcohol
sought care in the emergency department because of a 2-week
history of cough, hoarseness, and hemoptysis. He denied
dysphagia, weight loss, fevers, sweats, or chills. A chest radiograph revealed multiple bilateral pulmonary nodules. The
physical examination revealed a 3-cm thyroid nodule with
rightward deviation of the cervical trachea. FNA revealed
cytomorphologic features consistent with adenoid cystic carcinoma ❚Image 4❚ and ❚Image 5❚. A subsequent neck CT scan
showed involvement of the larynx and trachea with enlargement of the left thyroid lobe. A chest CT scan revealed
numerous peripheral solid pulmonary nodules consistent with
metastatic disease and a paratracheal mass that narrowed the
cervical trachea. Fiberoptic nasopharyngoscopy demonstrated
fixation of the left vocal cord in the paramedian position and
extramucosal compression of the left subglottis with no
discrete mass or ulceration. An incisional biopsy was
performed under local anesthesia, and confirmed the FNA
diagnosis of adenoid cystic carcinoma ❚Image 6❚. The patient
is currently receiving radiotherapy.
Cytology
Aspirates from both cases revealed highly cellular
smears with a monomorphic population of basaloid cells in
tight clusters. The individual cells were round, oval, or
© American Society for Clinical Pathology
Anatomic Pathology / ORIGINAL ARTICLE
❚Image 4❚ (Case 2) Adenoid cystic carcinoma. Fine-needle
aspiration. Medium-power aspiration cytology showing
classic hyaline globule and tight clusters of basaloid cells
(rapid Romanowsky, ×100).
slightly angulated with fine, granular chromatin and indistinct nucleoli. Cytoplasm was scant, and the cell borders
were indistinct. There were no definite grooves or intranuclear pseudoinclusions identified.
In case 1, there was an abundance of acellular material
resembling ropy colloid that was particularly noticeable on
the rapid Romanowsky–stained smears. We found no cribriform pattern or classic hyaline globules to suggest adenoid
cystic carcinoma. There was a vague microfollicle-like
pattern. The high cellularity, basaloid cells (interpreted as
follicular cells), ropy colloid, and the location within the
thyroid suggested a thyroid neoplasm (Images 1 and 2).
Papillary thyroid carcinoma, follicular variant, was favored.
In case 2, in addition to the same morphologic features
as present in case 1, a cribriform pattern and small hyaline
globules were present (Images 4 and 5). These features were
more suggestive of adenoid cystic carcinoma than a thyroid
neoplasm, despite the location in the thyroid. Thus, the
possibility of adenoid cystic carcinoma arising in the larynx
or trachea was raised before treatment.
Discussion
Thyroid nodules are relatively common and are found in
4% to 10% of the adult population.4 The majority of these
nodules are benign; only 5% are diagnosed as malignant.5
The most common primary malignant tumors of the thyroid
are papillary and follicular carcinomas. Medullary and
anaplastic carcinomas are uncommon. Even less frequent
❚Image 5❚ (Case 2) Adenoid cystic carcinoma. Fine-needle
aspiration. Medium-power aspiration cytology showing small
hyaline globules with round to oval cells with indistinct
nucleoli (rapid Romanowsky, ×100).
❚Image 6❚ (Case 2) Adenoid cystic carcinoma. Incisional
biopsy. Medium-power histologic stain of resected specimen
showing characteristic cribriform pattern of adenoid cystic
carcinoma (H&E, ×100).
primary malignant tumors include malignant lymphoma and
insular, giant cell, and squamous cell carcinomas.6 Although
metastatic tumors are uncommon in the thyroid, renal cell
carcinoma, breast carcinoma, endocervical adenocarcinoma,
and lung carcinoma have been identified.7 It is important to
always consider the diagnosis of metastatic disease in
patients with a thyroid mass, especially when there is a
history of cancer elsewhere.8
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Direct invasion of the thyroid by malignant neoplasms
from the laryngotracheal complex, although very
uncommon, is well documented. 9 The vast majority of
epithelial malignant neoplasms of the larynx and trachea are
of squamous origin.10 Nonsquamous carcinomas make up
fewer than 1% of all carcinomas of the laryngotracheal
complex, and adenoid cystic carcinoma is the most
prevalent.11
Adenoid cystic carcinoma arises from major and minor
salivary glands and accounts for one fourth of malignant salivary gland tumors. It is a slow-growing malignant tumor that
might be aggressive, with a high incidence of distant metastasis. Apart from the salivary glands, adenoid cystic carcinoma also has been reported in other locations, including the
breast, lung, larynx, and trachea.1,9-11 The morphologic
features of adenoid cystic carcinoma are similar, regardless
of site. There are 3 recognized histologic subtypes: tubular,
cribriform, and solid; the cribriform type is the most
common. Adenoid cystic carcinoma spreads by direct extension, perineural invasion, and hematogenous metastasis.11
Lymphatic spread is uncommon. 11 More than 50% of
patients with tracheal adenoid cystic carcinoma have
hematogenous spread, commonly to the lung.11 Direct extension of adenoid cystic carcinoma of the laryngotracheal
complex into the thyroid with clinical manifestation as a
thyroid nodule as illustrated herein, although uncommon, has
been reported previously.1,9 Since FNA often is used in the
evaluation of thyroid nodules, adenoid cystic carcinoma
might be encountered.
FNA is accepted widely as the most accurate, sensitive,
specific, and cost-effective diagnostic procedure in the
assessment of thyroid nodules.12 There are well-known
criteria used in the cytologic diagnosis of primary thyroid
tumors ❚Table 1❚. In the cytodiagnosis of thyroid lesions, the
cellularity/colloid ratio is the most useful criterion for separating nonneoplastic from neoplastic thyroid lesions. Careful
attention to the smear pattern, cell type, chromatin, and
nuclear features, such as grooves or pseudoinclusions, might
assist in the diagnosis. Therefore, there usually is little diagnostic difficulty when these classic features are present.
However, difficulties might arise when these features are
absent or subtle.
The diagnosis of adenoid cystic carcinoma often is less
problematic when the tumor is located in the salivary gland
and when its characteristic appearance on FNA cytology is
present. Smears are cellular with a monomorphic population of small basaloid cells with high nuclear/cytoplasmic
ratios, coarse chromatin, and small nucleoli (Table 1). Also
present are variable amounts of acellular hyaline stroma in
globular or cylindromatous formations typically identified
in aspirates of the cribriform and tubular subtypes. 13
However, reliance on these globules as the sole diagnostic
criterion might result in an erroneous diagnosis, especially
when adenoid cystic carcinoma is encountered outside the
salivary gland.
Case 1 illustrates how metachromatic material (hyaline
or basement membrane) in the context of a thyroid aspiration
was interpreted as ropy colloid. This miscue, in addition to
high cellularity and the presence of microfollicle-like structures resulted in the diagnosis of papillary thyroid carcinoma,
follicular variant. In addition to mimicking ropy colloid,
hyaline globules of adenoid cystic carcinoma also might be
mistaken for amyloid in aspirates of medullary carcinoma.
Other nonthyroidal neoplasms that have hyaline globule–like
material include pleomorphic adenoma, basal cell adenoma,
epithelial-myoepithelial carcinoma, polymorphous lowgrade carcinoma, and skin appendage tumors. These are all
extremely rare in the larynx and trachea and, thus, are very
unlikely to be found in the thyroid.
Case 2, in contrast, revealed the classic cribriform pattern
and hyaline globules of adenoid cystic carcinoma. A correct
diagnosis was made by aspiration cytology. Although adenoid
cystic carcinoma of the larynx or trachea invading the thyroid
is a rare occurrence (0.1% of the total thyroid FNA specimens
❚Table 1❚
Cytologic Features of ACC and Four Common Primary Thyroid Neoplasms
Cellularity
Pattern
Cytoplasm
Nucleus
Inclusions
Nucleoli
Chromatin
Mitoses
Background
elements
ACC
FTN
High
Cribriform or trabecular
Scant, basaloid
Oval to angulated
None
Small, indistinct
Coarse
Uncommon
Hyaline globules
High
Microfollicular
Minimal
Round
None
Small, distinct
Fine to coarse
Rare
No colloid
PTC
High
Papillae in sheets
Moderate, squamoid
Round with grooves
Intranuclear
Distinct
Powdery
Rare
Ropy colloid;
psammoma bodies
MTC
AC
High
Dispersed
Moderate, NE granules
Round to spindled
Intranuclear
Distinct
NE
Rare
Amyloid
High
Discohesive
Variable
Irregular
None
Large or multiple
Coarse
Numerous and atypical
Necrosis
AC, anaplastic carcinoma; ACC, adenoid cystic carcinoma; FTN, follicular thyroid neoplasm; MTC, medullary thyroid carcinoma; NE, neuroendocrine; PTC, papillary thyroid
carcinoma.
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in this institution in 10 years), it nevertheless should be
included in the differential diagnosis of a thyroid mass. This
is particularly important if there is clinical or radiologic
evidence of involvement of the laryngotracheal complex or if
cytopathologic examination reveals features of classic
adenoid cystic carcinoma.
If enough aspirate is obtained, immunohistochemical
analysis is helpful. Thyroglobulin and calcitonin can be
used to differentiate primary thyroid neoplasms from
secondary tumors. Primary thyroid neoplasms will express
thyroglobulin, thyroid transcription factor-1, and/or calcitonin (medullary carcinoma), while these antibodies will be
negative in adenoid cystic carcinoma ❚Image 7❚ and most
other tumors of extrathyroidal origin. It is important to note
that only the nuclear stain counts. Thyroid transcription
factor-1 is also usually expressed in carcinomas of the lung,
but these carcinomas are negative for thyroglobulin. In
addition, myoepithelial components of adenoid cystic carcinoma express muscle-specific actin and, occasionally, S100, which usually are absent in thyroid neoplasms.
The therapeutic implications of differentiating adenoid
cystic carcinoma of the larynx with direct extension to the
thyroid from invasive papillary carcinoma can be substantial.
Although both tumors are malignant, with surgery as the
mainstay of therapy, the required extent of surgery might
differ. Adenoid cystic carcinoma arising in the larynx or
trachea typically requires total laryngectomy and thyroidectomy for complete removal. However, depending on the
extent of laryngeal or tracheal involvement, papillary carcinoma invading the airway might be treated successfully by a
more conservative approach. Gross disease might be
“shaved” from the airway, thus preserving the larynx and its
function14 and providing survival rates comparable with
more extensive resection, including total laryngectomy. This
likely stems from the responsiveness of these tumors to postoperative radioactive iodine and external beam radiation, in
contrast with adenoid cystic carcinoma, which demonstrates
rather limited radiosensitivity.
❚Image 7❚ (Case 2) Adenoid cystic carcinoma. Incisional
biopsy. High-power immunohistochemical stain of resected
specimen showing absence of nuclear stain (thyroid
transcription factor-1, ×200).
Such lesions might arise in adjacent structures, as illustrated
by the cases described herein, or represent a metastasis to the
thyroid from a distant site. Although occasional misinterpretation might occur, error can be minimized by careful attention to cytologic criteria, incorporation of the available clinical and radiologic data, and the cytopathologist’s knowledge
of the broad differential diagnosis of thyroid masses.
From the Departments of 1Pathology and 2Ear Nose and Throat,
Virginia Commonwealth University Health System, Richmond.
Address reprint requests to Dr Powers: Dept of Pathology,
Virginia Commonwealth University Health System/Medical
College of Virginia Hospitals, PO Box 980662, Richmond, VA
23298.
References
Conclusion
In the evaluation of a thyroid nodule, history, physical
examination, and radiographic studies are essential but are of
limited usefulness, leaving treatment decisions to be heavily
reliant on the findings of aspiration cytopathology. Although
the majority of thyroid neoplasms will be primary to the
thyroid, the cytopathologist must be vigilant for tumors from
extrathyroidal sites. In patients with unusually aggressive
tumors, a history of previous or distant malignancy, or atypical
cytopathologic features noted in the aspiration specimen, the
possibility of a nonthyroidal neoplasm should be considered.
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