—  SPECIALTY CONFERENCE  —

Surgical Pathology

Case 5 - Follicular Ademona of Thyroid with Spindle Cell Metaplasia

Virginia A. Livolsi
University of Pennsylvania Medical Center
Philadelphia, PA


Click on each slide thumbnail image for an enlarged view
Clinical History
This 44 year old man presented with a 6 cm mass in his right thyroid. FNA attempted twice yielded insufficient material for diagnosis.

His family history was negative for thyroid disease or for cancer; he had no history of radiation exposure. Diagnosis:Follicular ademona of thyroid with spindle cell metaplasia


Case 5 - Figure 1 - (Labeled USCAP 2005 Silva x 10): Medium power view of the central part of the thyroid nodule which comprised about 90% of the 6 cm lesion (H&E stain).
Case 5 - Figure 2 - (Labeled VAL 04-1272-thyroid…): Spindle cell proliferation admixed with bland appearing colloid filled follicles. (H&E stain)
Case 5 - Figure 3 - (Labeled USCAP case 2005 X 20): High power shows focall nuclear enlargment and irregularity, but no mitoses or necrosis were identified. (H&E stain)


Spindle cell proliferations of the thyroid have been described in association with reactive processes and aggressive malignancies.They can be of primary thyroid origin or can arise secondary to metastatic disease. Lesions of primary thyroid origin can be derived from follicular, para-follicular/C-cell or mesenchymal components. They can present either as reactive proliferations as in the case of post-fine-needle aspiration spindle cell nodules of the thyroid (PSCNT), or as neoplastic processes such as anaplastic carcinoma, medullary carcinoma, solitary fibrous tumor and and other mesenchymal lesions. Distinction between these processes is critical as it dictates therapy and defines patient prognosis. Interpretation of these specimens can be difficult and requires immunohistochemical staining to determine the cellular origin of these lesions.

Of the various lesions in the differential diagnosis probably the one that needs to be recognized most is medullary carcinoma, since the implications for the patient and his/her family are vast. Medullary carcinoma constitutes <5-10% of thyroid malignancies and can occur with a familial or sporadic pattern of inheritance. In sporadic cases, women (> 50 years old) are most typically affected and present with a painless firm nodule typically in the lateral upper two thirds of the gland. Grossly, the lesions are circumscribed but infiltrative. Histologically, they are very variable and if composed of round to oval cells and if the stroma contains amyloid, there is usually little diagnostic difficulty. However, examples of spindled cell medullary carcinoma are not uncommon and may be distinguished by immunohistochemical staining for chromogranin, other neuroendocrine markers and most critically calcitonin.

Anaplastic carcinoma is the most aggressive thyroid neoplasm, but comprises only about 5-8% of all thyroid malignancies. Lesions typically occur in elderly patients who present with a rapidly enlarging neck mass. The lesions appear undifferentiated histologically and may possess spindle components as well as multinucleated giant cells; mitoses are frequent and often atypical, and necrosis may be extensive. Both the morphology and immunohistochemical profiles differ from the case herein described. In anaplastic carcinoma, the lesional cells demonstrate no reactivity with thyroglobulin, but may demonstrate reactivity with cytokeratin. There is often extensive intrathyroidal and extrathyroidal invasion and vascular invasion may be prominent; the prognosis is dismal.

Of the mesenchymal lesions that may arise in the thyroid as apparent primary neoplasms, tumors of smooth muscle, Schwann cell derivation and solitary fibrous tumors all have been described. The immunohistochemical profiles of these lesions indicate their mesenchymal nature and staining for desmin, actin, S100 protein and CD 34 would be helpful in these lesions; cytokeratin and thyroglobulin would be negative.

Rarely metastatic spindle cell tumors can present as thyroid masses; a variety of sarcomas have been reported including GI stromal tumors and leiomyosarcomas. In such cases, the history is important and often the thyroid lesion is a preterminal manifestation of systemic metastases.

With regard to reactive processes that may produce spindle cell patterns in the thyroid, the most frequent we have encountered is what we have termed the postFNA spindle cell nodule. Analogous to what has been described in posttraumatic lesions in the genitourinary tract, these lesions are predominantly histiocytic and vascular; inflammatory cells are a component of the lesion although these may vary in their numbers between different lesions. (Whether this may reflect the length of time between the FNA and the excision of the nodule or whether other factors are important is unclear.)

I believe the case presented represents something different. It was encapsulated and at its periphery it was composed of bland thyroid follicles. The bulk of the nodule especially centrally however, was composed of this spindle cell proliferation. However, there was minimal pleomorphism, minimal mitotic activity and no abnormal forms were noted; necrosis was not found. Immunostains showed that the cells of the lesion were positive for cytokeratin and thyroglobulin as well as TTF-1; negative reaction was obtained for calcitonin, CD 34, S100 and smooth muscle and vascular markers in the lesional cells. The staining pattern suggests that these represent metaplastic epithelial follicular cells producing the curious pattern.

We have previously described ten cases of spindle cell proliferations of the thyroid which arose in association with either papillary carcinoma or follicular adenoma. Subsequently I have seen 3 additional cases. The female-to-male ratio was 9:4 while patient ages ranged from 25 to 73 years. Of these thirteen spindle cell proliferations (including the panel case), 7 arose in association with papillary carcinoma, 5 arose in association with follicular adenoma and one within a minimally invasive follicular carcinoma.

The spindle components varied in their appearance, demonstrating diffuse as well as focal and multicentric nodular involvement of the underlying neoplasm and comprising anywhere from 1% to 95% of the tumor. In lesions with a diffuse pattern of involvement, the spindle cells formed areas of solid growth surrounding neoplastic glands . In comparison, lesions with a nodular pattern of involvement showed tightly woven spindle cells intermixed between follicles and/or glands of papillary carcinoma .

Cytologically, the spindle cells possessed either thin elongate or plump oblong nuclei with finely granular chromatin and subtle nucleoli . The cytoplasm was eosinophilic with indistinct cellular borders. Mitoses were rarely, if ever, identified within these spindle components and inflammation was minimal to absent.

A variant of papillary carcinoma of the thyroid exhibiting an exuberant nodular fasciitis-like or fibromatosis like stroma has been described. The lesion is comprised of short fascicles of spindle cells separated by a mucoid matrix, collagen and extravasated red blood cells. Immunostains demonstrated reactivity of the spindle cells with vimentin, S100 and occasionally desmin, but not with thyroglobulin. This lesion was, therefore, interpreted to be an exuberant mesenchymal reaction to the carcinoma.

Hermann has shown that cells isolated from both papillary carcinoma and follicular adenoma, when maintained in cell culture, undergo an epithelial-mesenchymal transition, assuming a fibroblastoid morphology and exhibiting reactivity with antibodies to cytokeratin, thyroglobulin and vimentin. Greenburg has shown a similar morphologic transformation in normal thyroid follicular cells suspended in a collagen matrix.

Appropriate identification of metaplastic spindle cell proliferations of the thyroid arising within papillary carcinomas and follicular adenomas can avoid confusion with more aggressive spindle cell processes and both morphologic and immunohistochemical assessment can assist in making this diagnosis. The most significant spindle cell lesion to be identified is anaplastic carcinoma, a highly aggressive malignancy that portends a poor prognosis.

Metaplastic spindle cell transformation of follicular derived lesions raises numerous questions of pathogenesis and potential tumorigenicity. Most of these lesions can be identified as follicular derived by the presence of a precursor lesion such as papillary carcinoma or follicular adenoma. However, in some cases the metaplasia can be so extensive that only the spindle cell component is identified.

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