See section nodular goiters
The greatest concern
relating to thyroid cytology lies in the fact that the cytological
investigation does not allow a differentiation between benign and
malignant follicular tumors. From a cytological aspect, therefore, it
seems reasonable to discuss follicular tumors in a common chapter,
although these tumors behave absolutely differently. A huge effort has
been made to find markers in order to discriminate between benign and
malignant follicular tumors preoperatively, but with only very limited
success. This is in no way a great surprise, when even a common
interpretation of the golden standard, histopathology, is not clearly
resolved (Saxen 1978). Moreover, a follicular pattern is often
seen in smears from non-tumorous thyroid lesions, and the distinction
between non-tumorous follicular thyroid lesions and follicular tumors
therefore involves a similar problem, naturally to a lesser extent, but
also within histopathological examinations (Rosai 1992).
The above-mentioned facts lead to two important consequences. First, a cytological diagnosis of follicular carcinoma is not accepted. Secondly, if we cannot achieve a cytological differentiation of benign and malignant follicular tumors, we need another aspect. US may have a great part to play in this field.
Theoretical reason for the difficulty in the differential diagnostics of follicular tumors
The cytological differential diagnostics of follicular tumors is based on a quantitative analysis of the cytological features. There is no other field in thyroid cytology where this quantitative analysis has such a great role in the differential diagnostic.
The only decisive sign in the histopathological diagnosis of a follicular tumor is the presence of a complete capsule surrounding a thyroid parenchyma; this is an absolutely qualitative sign.
The only decisive sign in the histopathological diagnosis of a follicular carcinoma is the demonstration of invasion of the tumor; this again is an absolutely qualitative sign.
The problem lies in the fact that, although the invasive nature of a follicular tumor is not independent of the cellular details (i.e. atypia, polymorphism or cluster formation), the relation between these features is primarily of statistical and not practical significance. Moreover, this relation is not linear as regards the various features investigated in cytology. This means that, except for the amount of colloid in the smear, there is no feature where the sequence nodular goiter-follicular adenoma-follicular carcinoma can be observed.
This chapter is
surprisingly short as regards the occurrence of follicular tumors and
the problems they cause. In our opinion there is no clear-cut evidence
for or against a follicular tumor in most thyroid lesions. The greatest
mistake that can be made is the cytological diagnosis of follicular
carcinoma. We must be aware that the relation between the cellular
atypia and the invasive nature of the tumor is uncertain, in contrast
with most other human tumors, where a close relationship does exist
between these features.
Cytological signs of follicular tumors
In a typical
(theoretical case) a follicular tumor is characterized by a background
without colloid, and by the presence of uniform follicular cells
forming folliculi of various sizes. Within these cases, atypical
follicular tumors (i.e. atypical adenoma and follicular carcinoma) are
characterized by nuclear polymorphism and the presence of small
abortive folliculi. On the other hand the cytological picture does not
permit a differentiation either atypical adenoma from highly invasive
follicular carcinoma or of minimally invasive follicular cancer from
the very common follicular adenoma. Moreover, in a significant
proportion of the cases, a clear distinction between nodular goiters
and follicular tumors is difficult or even impossible, see.
Some clues to the differential diagnostics of follicular tumors
A given follicular tumor is a heterogeneous lesion as regards the well-preserved, cellular parts. Even in cases of follicular carcinoma we can find regions with macrofollicular structures. This heterogeneity differs absolutely from that of anaplastic cancer for instance. In the latter disease, the heterogeneity means that part of the tumor is well preserved, while other parts are necrotic. The heterogenity of a follicular tumor is reflected in the cytology in the form of different cell types and different cell groups.
Some features on which the cytological differential diagnostics can be discussed:
The greater the amount the colloid in the smear, the lower the chance of a follicular tumor.
2. Follicular formation
The greater the
proportion of cells forming folliculi, the greater the chance of a
The greater the proportion of well-preserved microfolliculi, the greater the chance of microfollicular adenoma and minimally invasive follicular carcinoma.
The greater the proportion of small, irregular folliculi, the greater the chance of an atypical follicular tumor.
3. Cellular atypia
The greater the
occurrence of polymorphic cells in the smears, the greater the chance
of an atypical follicular tumor.
The greater the extent of anisonucleosis, the lower the chance of a follicular tumor (in cases without nuclear polymorphism).
The presence of enlarged cells without anisonucleosis is a very specific sign of a follicular tumor.
A follicular tumor or follicular variant of papillary cancer?
See Chapter on papillary cancer.