The term of poorly differentiated carcinoma was introduced by Sakamoto et al in 1983 and their criteria were based mainly on the presence of non-glandular components with a solid, trabecular, and scirrhous growth pattern. Others have included aggressive papillary thyroid carcinoma variants such as columnar cell, tall cell, diffuse sclerosing, and solid. The fact that these papillary thyroid cancer variants tend to show a more aggressive behavior pattern that the classic type of differentiated thyroid carcinoma does not in itself justify the use of term poorly differentiated, as defined by the tumor architecture. Furthermore, these tumors do not have an invariably poor prognosis. For example, the solid variant of papillary thyroid cancer displays some aggressive features, but patients tend to be younger and with appropriate treatment, their overall prognosis is similar to that of classic papillary thyroid cancer.
The insular carcinoma is the best characterized group of poorly differentiated carcinoma. Langhans fist described it in 1907 as “wuchernde strum” (proliferating struma). He described a tumor characterized by a distinct nesting pattern, formation of small follicular lumina leading to a cribriform configuration, small size and uniformity of the tumor cells, necrosis, and a focally peritheliomatous pattern of growth. It was reinterpreted and termed poorly differentiated “insular” thyroid carcinoma by Carcangiu et al in 1984. The term insular was used to describe these tumors because the cellular appearance was similar to that seen in the insular type of carcinoid tumors.
The insular carcinoma is the best characterized group of poorly differentiated carcinoma. Langhans fist described it in 1907 as “wuchernde strum” (proliferating struma). He described a tumor characterized by a distinct nesting pattern, formation of small follicular lumina leading to a cribriform configuration, small size and uniformity of the tumor cells, necrosis, and a focally peritheliomatous pattern of growth. It was reinterpreted and termed poorly differentiated “insular” thyroid carcinoma by Carcangiu et al in 1984. The term insular was used to describe these tumors because the cellular appearance was similar to that seen in the insular type of carcinoid tumors.
Definition
Follicular cell neoplasm that shows limited evidence of structural follicular cell differentiation and occupy both morphologically and behaviorally an intermediate position between differentiated (follicular and papillary carcinomas) and undifferentiated (anaplastic) carcinomas (1).
Etiology
The etiology is unknown. While some of these tumors appear to arise from preexisting papillary and follicular thyroid carcinomas, others most likely arise de novo.
The etiology is unknown. While some of these tumors appear to arise from preexisting papillary and follicular thyroid carcinomas, others most likely arise de novo.
Clinical features
Most poorly differentiated carcinomas appear as solitary large thyroid masses, cold by scintigraphy, with or without concurrent enlarged regional lymph nodes. Frequently, there is a history of recent growth in a long-standing uninodular or multinodular thyroid. Conversely, poorly differentiated carcinomas may occasionally present as rapidly growing masses. In addition to nodal metastasis, lung and bone metastases are also relatively frequent at the time of diagnosis.
Most poorly differentiated carcinomas appear as solitary large thyroid masses, cold by scintigraphy, with or without concurrent enlarged regional lymph nodes. Frequently, there is a history of recent growth in a long-standing uninodular or multinodular thyroid. Conversely, poorly differentiated carcinomas may occasionally present as rapidly growing masses. In addition to nodal metastasis, lung and bone metastases are also relatively frequent at the time of diagnosis.
Macroscopy
Most of tumors are over 3 cm in diameter at the time of diagnosis and are solid and gray-white with frequent foci of necrosis. Most tumors have pushing borders and, rarely, a thick capsule. In many cases there is also invasive, peritumoral growth that occasionally leads to satellite nodules within the thyroid parenchyma. Extrathyroidal extension is less commonly present than in undifferentiated entiated carcinomas.
Histopathology
The histopathological appearance of poorly differentiated thyroid carcinoma is variable. Three different histologic patterns are recognized: insular, trabecular, and solid. The diagnosis relies on the identification of these patterns in the majority of the tumor together with an infiltrative pattern of growth, necrosis, and obvious vascular invasion (Figure). Discrepancies do exist with regard to the significance of a minor poorly differentiated component in an otherwise well differentiated carcinoma, but on study has shown that the presence of more than 10 % of such pattern is associated with extrathyroidal invasion, and lymph node metastasis at the diagnosis. Some tumors display clear and oncocytic cells. Rarely these tumors may contain cells with rhabdoid features.
The insular pattern is characterized by well-defined nests of tumor cells surrounded by thin fibrovascular septa, which are frequently separated from tumor cells by artefactual cleft. The nest are predominantly solid, but may contain small follicles. Tumor cells are generally small and uniform and contain round hyperchromatic or vesicular nuclei with indistinct nucleoli. Mitotic figures are common (Figure).
The trabecular pattern is characterized by cells arranged in cords or ribbons, while the solid pattern exhibits large sheets of tumor cells that occasionally may show small abortive follicles or some colloid droplets. Poorly differentiated carcinoma may contain a minor component showing features of papillary or follicular carcinoma. Also some cases show focal nuclear pleomorphism, resembling an undifferentiated carcinoma. The presence of undifferentiated component should be reported because of some of these tumors have behaved as undifferentiated carcinoma.
The histopathological appearance of poorly differentiated thyroid carcinoma is variable. Three different histologic patterns are recognized: insular, trabecular, and solid. The diagnosis relies on the identification of these patterns in the majority of the tumor together with an infiltrative pattern of growth, necrosis, and obvious vascular invasion (Figure). Discrepancies do exist with regard to the significance of a minor poorly differentiated component in an otherwise well differentiated carcinoma, but on study has shown that the presence of more than 10 % of such pattern is associated with extrathyroidal invasion, and lymph node metastasis at the diagnosis. Some tumors display clear and oncocytic cells. Rarely these tumors may contain cells with rhabdoid features.
The insular pattern is characterized by well-defined nests of tumor cells surrounded by thin fibrovascular septa, which are frequently separated from tumor cells by artefactual cleft. The nest are predominantly solid, but may contain small follicles. Tumor cells are generally small and uniform and contain round hyperchromatic or vesicular nuclei with indistinct nucleoli. Mitotic figures are common (Figure).
The trabecular pattern is characterized by cells arranged in cords or ribbons, while the solid pattern exhibits large sheets of tumor cells that occasionally may show small abortive follicles or some colloid droplets. Poorly differentiated carcinoma may contain a minor component showing features of papillary or follicular carcinoma. Also some cases show focal nuclear pleomorphism, resembling an undifferentiated carcinoma. The presence of undifferentiated component should be reported because of some of these tumors have behaved as undifferentiated carcinoma.
Figure. Poorly differentiated thyroid carcinoma. The tumor has a trabecular (A), insular (B), and solid (C) growth patterns. D. The poorly differentiated carcinomas have obvious vascular invasion.Immunohistochemistry
Poorly differentiated carcinomas typically show immunoreactivity for thyroglobulin and TTF-1. Focal TP53 nuclear positivity and increased Ki-67 index is also common features. Most poorly differentiated carcinomas show absence of E-cadherin membranous expression in contrast to normal thyroid and well differentiated thyroid carcinomas.
Differential diagnosis
This includes medullary carcinoma, follicular carcinoma, metastatic carcinoma and solid variant of papillary carcinoma. Demonstration of positive immunostaining for thyroglobulin is useful in the distinction of these tumors from medullary and metastatic carcinomas. Rarely, poorly differentiated carcinomas may coexpress calcitonin and other neuroendocrine markers in scattered cells. Thyroid papillary carcinoma with solid areas usually occurs in young patients and exhibits typical nuclear features of ground-glass appearance and grooves.
Prognosis and predictive factors
The means survival ratio is about 50% in most series. The majority of patients die in the first three years after diagnosis and few patients survive >5 years. Death is usually caused by regional and distant metastases rather than by local invasion. The prognosis of patients with poorly differentiated carcinoma depends on primarily on the TNM staging, completeness of surgery and responsiveness to radiation iodine therapy. The prognostic significance of the prominence of necrotic foci, histologic pattern, extent of vascular invasion and degree of aneuploidy remains controversial. There is no sufficient evidence that any molecular genetic alteration plays a significant role in prognosis.
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