Case 5 -
Follicular Ademona of Thyroid with Spindle Cell Metaplasia
Virginia A. Livolsi
University of Pennsylvania Medical Center
Click on each slide thumbnail image for an enlarged view
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
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
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
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
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
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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