Follicular Carcinoma

Follicular carcinoma accounts for 5-15% of all thyroid cancers in iodine-sufficient areas. It is more common in women and presents on average about 10 years later than papillary carcinoma. It is usually a single "cold" nodule. Occasional cases present as distant metastases, particularly in bone. On the basis of the extent of invasion, the tumor is subdivided into two categories - minimally and widely invasive. Minimally invasive tumors are more common. These are diagnosed on the presence of microscopic capsular and/or vascular invasion. Widely invasive tumors can often be seen infiltrating the normal gland by naked eye examination. This diagnosis may also be applied when extensive vascular invasion is identified at microscopic level. It is important to make the distinction between the two, as the outcome varies significantly. The 10-year survival rate for minimally invasive disease is 70-100% and for the widely invasive type, 25-45% [21]. Tumor-related deaths are more common in the widely invasive group, reported in 20-50% of cases, but in minimally invasive disease may only account for 3% of deaths [19,22].

Minimally Invasive Thyroid Cacinoma
Figure 9.3 Minimally invasive follicular carcinoma showing capsular invasion. The tumor can be seen extending in mushroom-like fashion through the fibrous capsule, which shows "blunt ended"breaks.Compressed normal thyroid is seen to the top left of the figure.

Grossly, minimally invasive follicular carcinoma resembles follicular adenoma, although it often has a thicker capsule. Diagnosis depends on the identification of capsular (Figure 9.3) and/or vascular (Figure 9.4) invasion on histo-logical examination. There has been debate over the years as to the definitions of these two features. It is now generally accepted that tumor cells must penetrate the entire thickness of the capsule to diagnose capsular invasion. This is usually associated with "blunt end" breaks in

Figure 9.4 Minimally invasive follicular carcinoma showing vascular invasion.Tumor is seen within an intracapsular vessel. It is attached to the wall of the vessel in the lower part and is covered by endothelium.

the capsule and a "streaming" or mushroom pattern of growth of tumor through the capsule. This is in contrast to the entrapment of follicles within the capsule of an adenoma where there is no impression of an active process of cell movement. It is important to realize that the penetrating tumor mass often stimulates the formation of a new capsule. This means that the tumor may have a dumbbell appearance, or that there is the impression of subdivision of a follicular tumor by a fragmented fibrous band.

These appearances can be extremely difficult to interpret. Historically, some pathologists argued that malignant potential could not be diagnosed on the basis of capsular invasion alone and defined these tumors as "follicular neoplasms of undetermined malignant potential." However, metastases have occurred in tumors where only capsular invasion has been identified.

Vascular invasion is diagnosed only when tumor thrombi are attached to the wall of a medium sized or large vessel, either within or outside the capsule, and are covered by endothe-lium. It should be noted that tumor cells and vessels are often intermingled within the capsule, and it can sometimes be difficult to assess whether this is true invasion. It may be necessary to use immunohistochemistry for an endothelial marker such as CD 31 or CD 34 to define this. Factor VIII-related antigen is not generally useful, as it can be negative in vessels invaded by tumor. An unusual feature that might also be misinterpreted as invasion is endothelial hyperplasia in capsular vessels. However, if this is seen, it should prompt a search for vascular invasion, as it has usually been reported in carcinomas [23].

Immunohistochemistry has been applied in an attempt to distinguish benign and malignant lesions. Widespread strong positivity for galectin-3 would support a malignant diagnosis, but more focal staining can be found in benign follicular lesions and not all carcinomas are positive [8,24]. HBME-1 also stains malignant lesions more commonly than benign [25]. Ancillary techniques such as ploidy analysis have no role in making the distinction between adenoma and carcinoma.

Widely invasive tumors are usually easy to define. Grossly, the tumor can be seen infiltrating the normal gland. Some have no evidence of a capsule, while others have a capsule with extensive capsular and vascular invasion.

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