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Approach - To - FNA - of - Thyroid - Gland - Cysts.5.pdfL P 4
Approach - To - FNA - of - Thyroid - Gland - Cysts.5.pdfL P 4
358 | www.anatomicpathology.com Adv Anat Pathol Volume 29, Number 6, November 2022
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Adv Anat Pathol Volume 29, Number 6, November 2022 Thyroid Gland Cysts
TABLE 1. Cytologic Criteria for Nondiagnostic Cystic Lesions (According to the Bethesda Thyroid System)
Morphologic Criteria Management
Nondiagnostic cystic It contains only macrophages with a noncohesive pattern, Reaspiration necessary only if
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lesions characterized by abundant cytoplasm with brown hemosiderin ultrasound features are suspicious
pigment in some of them
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Herein we aimed to identify the US risk factor and the watery colloids without follicular cells (Fig. 1). A partially
cytologic features able to discriminate benign versus cystic thyroid nodule show sheet or aggregates of thyrocytes
malignant cystic thyroid nodules so that a standard (with benign and/or malignant features-according to the
approach can be followed for these lesions nature of the lesion) admixed with a background composed
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Rossi et al Adv Anat Pathol Volume 29, Number 6, November 2022
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FIGURE 2. A, B, A partially cystic nodule. The nodule showed few US suspicion features so that an fine needle aspiration cytology was
performed with LBC. The cytological findings show few clusters of small and benign follicular thyroid epithelial cells with numerous
macrophages diagnosed as a benign partially cystic adenomatous nodule (LBC-20X, and ×40). LBC indicates liquid based cytology.
Please see this image in color online.
System (TIRADS),28 further modified by Kwak et al.13 It diagnostic accuracy, confirming that the US characteristics
was based on the American College of radiology’s breast can be used to prioritize nodules for FNAC.17
imaging reporting and data system (BI-RADS). It was Kim et al compared 26 patients with benign cystic
accepted and then proposed by the American College of nodules showing marked US hypoechogenicity and 38
Radiology (ACR), which is based upon the distribution of patients with marked US hypoechogenicity in the US sus-
US features in five categories (composition, echogenicity, picious for PTC.34 While the authors did not find any dif-
shape, margin, and echogenic foci).29 According to the ference in nodular size, margin, echogenic dot and vascu-
system, cystic lesions or lesions that are almost completely larity, they documented significant differences in the
cystic are benign and no further points will be added nodular shape between the 2 groups with a lower prevalence
TI-RADS 1). Similarly, in the other US classification of taller than wide in the benign cystic group (11.5% vs.
systems,10–14 cystic and partially cystic lesions are scored as 39.5%, P = 0.022).
benign. Park et all compared the US characteristics of 22 sur-
Several studies analyzed the US features and ROM for gically confirmed partially cystic papillary carcinomas, and
cystic lesions, combining them with the cytologic classi- compared them with those of 80 benign partially cystic
fication systems, mostly with the Bethesda thyroid nodules.35 They assessed that malignant partially cystic
system.30–33 thyroid nodules had a taller-than-wide shape (100%,
In a series of 1342 thyroid lesions by Li et al, 281 P < 0.001) and spiculated or microlobulated margin (58.3%,
(20.7%) cases were partially cystic lesions with fewer than P = 0.003). Other additional features linked with malig-
5% malignant outcome. The evaluation of the US features nancy are represented by eccentric configuration (68.0%,
demonstrated 84.6% sensitivity, 84% specificity and P < 0.001), non-smooth margin (81.3%, P < 0.001), hypo-
echogenecity (30.0%, P < 0.042), and microcalcification
(89.5%, P < 0.001).
In another study, Peng et al discussed the diagnostic
accuracy of US in differentiating papillary thyroid micro-
carcinomas (PTMCs) from cystic thyroid nodules mimick-
ing malignancy, in nodules smaller than 10 mm in
diameter.36 The series included 162 cystic lesions and 150
PTMCs evaluated for US parameters. They concluded that
shape, rim calcification, and vascularity are valid criteria to
distinguish them.
Koo et al compared the US features of 33 cystic nod-
ules, which can mimic malignancies, after fine-needle aspi-
ration (FNA) with 47 malignant nodules.37 They reported
that all the cystic lesions were benign histology even though
several of their cystic nodules after aspiration were similar to
PTCs in their sonographic findings. Nevertheless the former
had shadowing and a halo (85% vs. 21%; P < 0.0001).
Lee et al included 392 partially cystic nodules which
were subclassified into 3 groups based on the amount of the
FIGURE 3. Ultrasound evaluation of a benign cystic thyroid solid portion: (1) nodules in which the solid portion was
nodule. Details pf the cystic component are evaluated during the
US exam leading to the decision of performing an fine needle
<50%; (2) nodules with the solid portion > or = 50%; and
aspiration. group 3 included mixed echoic (spongy) nodules.19 The
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Adv Anat Pathol Volume 29, Number 6, November 2022 Thyroid Gland Cysts
benign lesions with a malignancy rate of 5.4%. Considering Nondiagnostic Cystic papillary thyroid carcinoma
the 3 different subgroups, the highest malignant rate was Goiter Cystic medullary thyroid carcinoma
found in group 2, while it was 0 in group 3. Furthermore,
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After FNAC, 506 of the patients with solid masses (11.9%) multiple well-defined vacuoles, favor PTC over benign his-
underwent surgical treatment, compared with 143 of those with tiocytes. Furthermore, immunocytochemical studies can
cystic lesions (7.2%). They also evaluated the malignant rate, also be useful in confirming the diagnosis.46 A detailed
which resulted in 29.8% for the solid group and 9.1% for the evaluation of these atypical cells is necessary to preventing
cystic lesions. This data confirmed that the diagnostic accuracy false-negative diagnosis of PTC.
of FNAC in cystic masses after ultrasonographic examination In another paper, Renshaw reviewed a large series of
resembled that in solid thyroid nodules. thyroid aspirates for specimens with unusual cells defined by
Liu et al in a study of 94 partially cystic nodules dis- vacuolated, histocyte-like features without classic nuclear
cussed the sonographic features that can be predictive evi- changes of papillary carcinoma. These histiocytoid cells
dence of malignancy and they assessed the diagnostic effi- were recognized in 6% of the samples analyzed. The mor-
cacy of these features.39 In detail, the authors demonstrated phologic evaluation demonstrated that these cells resembled
that microcalcification, hypoechogenicity, and a solid com- histiocytes but were larger, more atypical, and keratin pos-
ponent ≥ 50% of the total volume were associated with itive in the one specimen that was tested. The cells had
97.6% sensitivity, 32.7% specificity, 53.9% positive pre- enlarged nuclei with abundant cytoplasm that often was
dictive value (PPV), and 94.4% negative predictive value vacuolated. The awareness of their finding in thyroid FNAC
(NPV). The evaluation of these 3 parameters might be is likely to improve the accuracy of cytology.47
helpful in the diagnosis of partially cystic lesions. Although cystic colloid goiter and other cystic neo-
Ko et al studied the US features of 13 collapsing benign plasms can be easily recognized on FNAC, the possibility to
cystic nodules (spontaneously or after FNAC) that dis- differentiate cystic PTC from cystic adenomatous nodules is
tinguish such nodules from 26 malignant thyroid nodules.40 difficult because of the common features. In fact, in both
Their study included the evaluation of many US findings entities we might recognize foamy macrophages, atypical
such as internal content, shape, margin, echogenicity, pres- histiocytes, spindle cells, squamous cells, anisonucleosis,
ence of echogenic dots suggesting microcalcification and multinucleated giant cells, and calcification. Furthermore,
macrocalcification, inner isoechoic rim, and low-echoic cells from PTC may show cytoplasmic hypervacuolization
halo. Their data confirmed that US features helpful for and “bubble gum colloid”.
differential diagnosis of CBCNs from PTMCs include In a series by Mokhatari et al,48 including 73 cases of
shape, margin, and the presence of an inner isoechoic rim cystic PTC, the authors found some peculiar features rep-
and a low-echoic halo. resented by small clusters with scalloped margins, cellular
swirls, and clusters with a cartwheel pattern.
MALIGNANT CYSTIC THYROID LESIONS
It is estimated that ~23% of the thyroid cystic lesions
are proved to be malignant41–45 (Table 2).
According to the literature, follicular neoplasms, PTC,
and medullary thyroid carcinoma (MTC) may have cystic
components, even though their scant cellularity is likely to
cause false-negative diagnosis.4
Among the malignant lesions, papillary thyroid carci-
noma (PTC) may be characterized by cystic changes more
frequently than other thyroid neoplasms4,41–45 (Fig. 4). The
FNA diagnosis of cystic thyroid lesions can be very tricky,
especially owing to low cellularity with some of these few
cells characterized by nuclear atypia and prominent nucleoli
mimicking thyroid malignancy, especially PTC. Fur-
thermore, the evidence of metaplastic squamous cells in
benign cysts can lead to a misdiagnosis of a malignant
tumor, and, to note, the histiocytoid epithelial cells in PTC
may be confused as histiocyte.41–45 Hashan et al discussed
the possibility that PTC presents rarely with aberrant fea- FIGURE 4. A partially cystic papillary thyroid carcinoma (PTC).
tures resembling those of histiocytes in a cystic nodule. The sample is composed of follicular thyroid epithelial cells
These atypical histiocytes can be seen in cystic thyroid showing the nuclear features of PTC in a background with several
lesions. Nevertheless, the morphologic features including macrophages (LBC, 40X). LBC indicates liquid based cytology.
large cell size, pseudoinclusions, nuclear grooves, and Please see this image in color online.
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Rossi et al Adv Anat Pathol Volume 29, Number 6, November 2022
Evaluation
Suspicious of US solid Benign features
features
FNAC FNAC
(if large cystic Clinical and/or
mass) surgical FU
(based on the
nodular size)
FU based on FU based on
FNAC size
Lin and Huang45 compared the accuracy of US and a water-clear fluid mostly suggests parathyroid cysts,
FNAC in diagnosing cystic thyroid cancer Versus solid although a yellowish to brown cystic material is seen in
thyroid cancers. They included 682 thyroid malignant thyroid cysts/pseudocysts. To note, occasionally PTC can be
lesions subdivided as 583 (85.5%) solid masses, 80 (11.7%) diagnosed in thyroglossal duct cysts.53–55 Furthermore, a
mixed masses, and 19 (2.8%) cystic masses. Among the case report by Rumman et al described a thyroglossal
latter group of 19 cystic thyroid carcinoma, only 4 PTC 5×5 cm mixed solid and cystic mass in mid neck resulting in
were diagnosed as malignant on both US and FNAC. They a histopathological diagnosis of a poorly differentiated
concluded that the low rate of accurate diagnosis for the carcinoma of insular type.58
cystic malignancy did not affect both the clinical staging and
the survival rates.
Henrichsen et al studied 380 thyroid nodules including MANAGEMENT OF CYSTIC LESIONS
33 either partially (< 50% cystic component) or 9 exten- The majority of cystic and partially cystic lesions are
sively cystic nodules ( > 50% cystic component of the nod- asymptomatic so that the treatment is unnecessary.59–62
ule). They concluded that 88% of thyroid cancers are solid Nonetheless, some of them are likely to represent a palpable
or with minimal (1–5%) cystic change. Only 2.5% of cancers mass with cosmetic problems or other complaints. To solve
had a significant cystic component and they also show some these latter issues, the well-established, non-surgical treat-
other sonographic findings worrisome for malignancy.49 ment includes a simple aspiration to reduce/eliminate the
MTC usually is a solid malignant lesions, even if it cystic lesion and/or ethanol ablation.59–62 The former is
rarely shows a cystic component. As reported by Fadda usually the first option for the treatment of a cystic lesion,
et al,50 some hemorrhagic changes in medullary carcinomas, leading to both a diagnosis and a reduction of the cystic
mostly owing to presurgical FNAC, have been described. volume. However, several cases have recurrences after
Nevertheless, immunohistochemistry and/or serum calcito- aspiration (from 50% to 80% of them), or if they show a
nin levels will help to solve the diagnostic dilemma in such stronger viscosity difficultly aspirated with needles, US-
cases.3,4 guided ethanol ablation has been recommended and it is
Despite the fact that any malignant lesion is likely to associated with good yields ranging from 68% to 97%
have a cystic component, it is rare for other malignant (58-61). The algorithm approach suggests to firstly identify
lesions if the lesions are completely and partially cystic nodules. In
fact, based on this first discrimination, completely cystic
nodules can be clinically or surgically followed-up according
OTHER CYSTIC LESIONS to the nodular size and symptoms. The performance of an
Thyroglossal duct cysts, parathyroid cysts, epidermoid FNAC would result in macrophages and hemorrhagic-col-
cysts, branchial cleft cysts can all occur either in the thyroid loid debris, diagnosed in the ND category. In cases of a
or around the thyroid (lateral midline cysts).3,4,50–52 These partially cystic lesion, the US evaluation is the leading guide
entities are rare with an incidence of 0.6 to 3% for para- for the further management. In fact, if there are some US
thyroid cysts, 7% for thyroglossal cysts. The presence of suspicious features, an FNAC should be performed fol-
ciliated cells, lymphocytes, squamous, colloid, and keratin lowed by clinical or surgical follow-up based on the cyto-
are useful for the differential diagnosis.50–57 The presence of logic diagnosis. In cases without any evidence of suspicion
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Adv Anat Pathol Volume 29, Number 6, November 2022 Thyroid Gland Cysts
for malignancy, the decision of clinical and/or surgical fol- 14. Na DG, Back JH, Sung JY, et al. Thyroid imaging reporting
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