Aggressive Variants of Follicular Cell Derived Thyroid Carcinoma
Aggressive Variants of Follicular Cell Derived Thyroid Carcinoma
A solid growth pattern is noted focally in many papillary carcinomas. When the solid growth represents >50% of the tumour mass, a diagnosis of solid variant (SV) of papillary carcinoma may be made. The SV is most commonly seen in children and its incidence is 10% in sporadic PTC and >30% of patients with papillary carcinoma after the Chernobyl nuclear accident. It usually presents as a solid nodule with infiltration into the surrounding thyroid parenchyma. By light microscopy the tumour shows solid nests of tumour cells with nuclear features of papillary carcinoma, separated by delicate to broad collagenous bands (figure 4). Some tumours may show focal areas of follicular and papillary architecture. The nuclear features are those of papillary carcinoma, although the nuclei tend to be more rounded than oval. About 40% of these tumours show vascular invasion and ETE (figure 4).
(Enlarge Image)
Figure 4.
Solid variant: Solid nests of tumour cells showing nuclear features of papillary thyroid carcinoma (H&E stain, 40×).
Although some studies particularly from Japan have considered the solid papillary carcinoma as a poorly differentiated tumour with a guarded prognosis, in North America and Europe, this has not been found. It is important to recognise these lesions as papillary carcinomas and not overdiagnose them as more aggressive tumours such as poorly differentiated (insular) carcinoma. Papillary and non-papillary cancers of the thyroid can demonstrate areas of solid growth and/or insular growth patterns. We believe that these two should be morphologically separated; the areas of insular carcinoma usually show well-defined nests of monotonous tumour cells with round nuclei and scant cytoplasm. Loose connective tissue stroma and prominent vascularity separate the tumour nests from each other. Occasionally these areas may show foci of tumour necrosis. Albores-Saavedera et al described five cases of the macrofollicular variant of papillary carcinoma that exhibited a minor insular transformation. All these patients survived albeit with metastasis in 40%, these authors believed that the presence of the insular component did not alter the excellent prognosis associated with papillary carcinoma. Similar findings were reported by Ashfaq et al, who found that the aggressive clinical behaviour of tumours with focal insular change is more dependent on age of patient and tumour stage rather than insular growth pattern.
SV does occur in adults and in our experience, over a third of these arise in patients with systemic autoimmune disease. The inter-relationship of these disorders is unknown. The prognosis of SV of papillary carcinoma is almost as good as classic papillary carcinoma, in children and in adults. They do not have the guarded prognosis of poorly differentiated carcinoma, even in the presence of necrosis.
Molecular analysis of cases of SV-PTC arising in association with radiation exposure has shown RET/PTC rearrangement. The RET/PTC3 rearrangement has been more frequently associated with SV-PTC which is considered the most prevalent variant among the irradiated tumours. With the increase in latency period the prevalence of the SV and the RET/PTC rearrangements has declined suggesting a strong relationship between radiation exposure, SV and RET/PTC3. Interestingly, a triplet deletion of the BRAF gene leading to the replacement of a valine and a lysine by a glutamate (BRAF V600E+K601), was first reported only in the SV of PTC by Trovisco et al; which has been confirmed by other investigators.
Solid Variant
A solid growth pattern is noted focally in many papillary carcinomas. When the solid growth represents >50% of the tumour mass, a diagnosis of solid variant (SV) of papillary carcinoma may be made. The SV is most commonly seen in children and its incidence is 10% in sporadic PTC and >30% of patients with papillary carcinoma after the Chernobyl nuclear accident. It usually presents as a solid nodule with infiltration into the surrounding thyroid parenchyma. By light microscopy the tumour shows solid nests of tumour cells with nuclear features of papillary carcinoma, separated by delicate to broad collagenous bands (figure 4). Some tumours may show focal areas of follicular and papillary architecture. The nuclear features are those of papillary carcinoma, although the nuclei tend to be more rounded than oval. About 40% of these tumours show vascular invasion and ETE (figure 4).
(Enlarge Image)
Figure 4.
Solid variant: Solid nests of tumour cells showing nuclear features of papillary thyroid carcinoma (H&E stain, 40×).
Although some studies particularly from Japan have considered the solid papillary carcinoma as a poorly differentiated tumour with a guarded prognosis, in North America and Europe, this has not been found. It is important to recognise these lesions as papillary carcinomas and not overdiagnose them as more aggressive tumours such as poorly differentiated (insular) carcinoma. Papillary and non-papillary cancers of the thyroid can demonstrate areas of solid growth and/or insular growth patterns. We believe that these two should be morphologically separated; the areas of insular carcinoma usually show well-defined nests of monotonous tumour cells with round nuclei and scant cytoplasm. Loose connective tissue stroma and prominent vascularity separate the tumour nests from each other. Occasionally these areas may show foci of tumour necrosis. Albores-Saavedera et al described five cases of the macrofollicular variant of papillary carcinoma that exhibited a minor insular transformation. All these patients survived albeit with metastasis in 40%, these authors believed that the presence of the insular component did not alter the excellent prognosis associated with papillary carcinoma. Similar findings were reported by Ashfaq et al, who found that the aggressive clinical behaviour of tumours with focal insular change is more dependent on age of patient and tumour stage rather than insular growth pattern.
SV does occur in adults and in our experience, over a third of these arise in patients with systemic autoimmune disease. The inter-relationship of these disorders is unknown. The prognosis of SV of papillary carcinoma is almost as good as classic papillary carcinoma, in children and in adults. They do not have the guarded prognosis of poorly differentiated carcinoma, even in the presence of necrosis.
Molecular analysis of cases of SV-PTC arising in association with radiation exposure has shown RET/PTC rearrangement. The RET/PTC3 rearrangement has been more frequently associated with SV-PTC which is considered the most prevalent variant among the irradiated tumours. With the increase in latency period the prevalence of the SV and the RET/PTC rearrangements has declined suggesting a strong relationship between radiation exposure, SV and RET/PTC3. Interestingly, a triplet deletion of the BRAF gene leading to the replacement of a valine and a lysine by a glutamate (BRAF V600E+K601), was first reported only in the SV of PTC by Trovisco et al; which has been confirmed by other investigators.
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