Follicular Variant of Papillary Carcinoma

This is the next commonest variant to the classic variant of papillary carcinoma. It is characterized by follicular architecture, but the cells lining the follicles have the cytological features of papillary carcinoma. Where a mixed pattern of classic papillary and follicular architecture is present, the tumor should be classified as a classic variant. Most of these tumors are not encapsulated or have a poorly formed capsule. Prominent fibrous bands may extend between the tumor cells. The follicles are often of irregular shape with abortive attempts to produce papillae. There may also be interconnections between neighboring follicles [34]. The presence of multinucleate cells within the lumen of the follicles is another clue to diagnosis. These have a histiocytic phenotype [35]. Where these features are pronounced and present throughout the tumor, the diagnosis can be easy. However, in some tumors, the changes are more focal in distribution and distinction has to be made from follicular tumors or hyperplastic nodules. This can be difficult. A panel of antibodies has been proposed. These include cytok-eratin 19 (CK19) (Figure 9.6), HBME-1, and RET. In a series of 84 cases of papillary carcinoma, 57% were positive for CK19, 45% for HBME-1, and 63% for RET protein. Only seven cases were negative with all three proteins [36].

Black And White Marble Pebble Florim
Figure 9.6 A follicular area in a papillary carcinoma of thyroid showing positivity for cytokeratin 19.
Galectin Cancer
Figure 9.7 A follicular variant of papillary carcinoma showing widespread positivity for galectin-3.The follicles contain multinucleated histiocytic giant cells, which are associated with papillary carcinoma.

Strong diffuse staining for cytokeratin 19 is usually seen in the areas with nuclear changes, with weaker staining in the rest of the tumor. This contrasts with the focal reactivity that can be seen in follicular tumors. Papillary carcinomas are often positive for galectin-3 (Figure 9.7) [37,38]. Immunostaining with the antibodies to RET protein is an alternative approach, but there are no robust antibodies currently available commercially. In a few cases, it is extremely difficult to be sure of the diagnosis, and even endocrine pathologists will disagree as to how to categorize the lesion. It may be appropriate to say that the diagnosis of FVPC cannot be fully excluded. The development of multidisciplinary teams will allow discussion of how to proceed in these cases.

There are a number of patterns of growth of FVPC within the gland and it is important to recognize these as the behavior may differ. About 30% are encapsulated and have a good prognosis. Some tumors invade widely - the diffuse type [39]. These form multiple nodules throughout the gland and are commonly associated with lymph node and distant metastases Another group is the macrofollicular variant [40]. On low power, foci of tumor resemble hyperplastic nodules and the differential diagnosis may include macrofollicular adenoma or nodular goiter. The recognition of the nuclear features is important in making these distinc tions. This tumor has a low rate of lymph node metastases.

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