Spindle Cell Transformation of Papillary Carcinoma: An Aggressive Entity Distinct From Anaplastic Thyroid Carcinoma Open Access

Anaplastic thyroid carcinoma (ATC) typically appears as an extremely pleomorphic neoplasm composed of multinucleated tumor giant cells and bizarre spindle cells. Its fierce histologic anaplasia is matched by an aggressive clinical course. Rarely, ATC can result from transformation of well-differentiated thyroid carcinoma; this is a well-recognized outcome for a small subset of patients with papillary thyroid carcinoma (PTC). We report an unusual variant of anaplastic transformation of PTC. This tumor was characterized by a proliferation of bland to intermediate-grade spindle cells admixed with PTC. Although this transformation did not resemble ATC histologically, the clinical course was similar to that of typical ATC. The patient suffered early aggressive recurrence and pulmonary metastases leading to her death. The unique nature of this neoplasm merits publication and wider recognition. Furthermore, we discuss the similarities and distinctions between this tumor and other spindled thyroid neoplasms.

An 82-year-old woman presented to our institution in 1997 with a large neck mass eroding the skin; she also suffered rapidly progressing dyspnea, which required tracheostomy. Her past surgical history was noteworthy for a previous right thyroid lobectomy performed in 1944, the pathology of which was unknown. It was also unknown if she had received any prior radiation to the neck. In 1995, completion thyroidectomy was performed for PTC; further pathologic details for this specimen were also unavailable. Radiographic examination in 1997 revealed a large mass in the central compartment of the lower neck, extending into the upper mediastinum. Fine-needle aspiration at that time revealed a bland spindle cell infiltrate. A needle biopsy at that time revealed a “mitotically active fibroblastic proliferation, consistent with a desmoid-like or Riedel's struma-like process.” Total laryngopharyngectomy was performed. The patient developed locoregional recurrent disease and pulmonary metastases after 5 months and died soon thereafter. No autopsy was performed.

The resection consisted of a total laryngectomy and resection of overlying subcutaneous tissue and skin. The specimen was remarkable for a tan, multilobulated, infiltrative, soft, rubbery mass, 14 cm in greatest dimension, which ulcerated the skin. Hemorrhagic foci were present within the lesion. The tumor extended grossly into the trachea. Frozen section analysis revealed a biphasic spindle neoplasm with possible PTC components. Permanent sections revealed that the tumor was composed predominantly (>95%) of relatively bland spindle tumor cells of low to intermediate grade (Figure 1). We noted no appreciable collagen deposition. Atypical mitotic figures were present, but necrosis was not seen (Figure 2). The spindle cell neoplasm was primarily situated in the anterior soft tissue compartment, but extended into the endolarynx. Epithelial elements of PTC were admixed within the spindle cell neoplasm (Figure 3). At times, discreet glandlike elements could be seen (Figure 4). In other areas, the epithelial elements appeared as epithelioid whorls admixed within the spindle cell neoplasm, reminiscent of biphasic synovial sarcoma. No pronounced tall cell component was seen. Transition from the epithelial elements to spindle cell formation was appreciated (Figure 5). No areas of keratinization were seen. The adjacent lymph nodes were negative. However, vascular tumor emboli composed of the spindle cell element were present.

Immunohistochemical studies revealed that the spindle cells expressed vimentin (Dako Corporation, Carpinteria, Calif), but were negative for desmin (Dako), muscle-specific antigen (Enzo, Farmingdale, NY), S100 protein (Dako), factor XIIIa (Calbiochem-Novabiochem, San Diego, Calif), low- and high-molecular-weight cytokeratins (Signet, Dedham, Mass), epithelial membrane antigen (Dako), and thyroglobulin (Dako). The epithelial PTC component expressed thyroglobulin (Figure 6), epithelial membrane antigen, S100, and AE3. Electron microscopy revealed 2 components: typical thyroid follicular epithelium plus spindle cells separated by significant collagen matrix. These spindle cells formed small desmosomes and produced patchy basement membrane. Their nuclei, although elongated, had the same features as the epithelial component. Cytoplasmic electron-dense granules, granular endoplasmic reticulum, and some Golgi complexes were present in both spindle and epithelial cells. Thus, the ultrastructural study confirmed that there were 2 distinct growth patterns, that is, PTC with a prominent spindle cell component (spindle cell carcinoma).

Wildly pleomorphic malignant spindle cells are often seen in ATC. Bland reactive fibroblasts can be seen in benign conditions, such as Riedel struma and de Quervain granulomatous thyroiditis. Spindle epithelial tumor with thymuslike differentiation of the thyroid (SETTLE) is a rare thyroid spindle cell carcinoma of putative intrathyroid thymic rest origin. Medullary thyroid carcinoma can contain malignant spindle cells that uniquely express calcitonin. With the exception of these well-described entities, spindle cells are not routinely encountered in the context of thyroid pathology.

Bronner and LiVolsi1 reported a spindle cell variant of squamous cell carcinoma as an unusual variant of anaplastic transformation within PTC. The 5 tumors described in their article were composed of spindled squamous cell carcinoma cells intimately admixed with tall-cell PTC. The squamous component formed discrete islands, some with keratinization, and merged into the malignant spindle cells. The spindle cells ranged from moderately to markedly pleomorphic. No multinucleated tumor giant cells were described, as would be seen in ATC. Immunohistochemical investigation revealed that the spindle cells expressed low-molecular-weight cytokeratin in 3 of 5 cases, but expression was strong in only 1 of these cases. No spindle cell component in any of these cases expressed thyroglobulin. Chan and colleagues2 described an “exuberant nodular fasciitis–like stroma” in association with PTC. Unlike the tumors reported by Bronner and LiVolsi, no squamous differentiation was seen in their 3 cases. The spindle cells in these cases were not pleomorphic or mitotically active. They were intimately admixed with the PTC, separating this component to impart a phyllodes tumor–like appearance. Unlike the tumors described by Bronner and LiVolsi,1 these spindle cells expressed neither cytokeratin nor thyroglobulin. The authors did not comment as to whether transformation from the PTC to the spindle cell component was observed. However, we can assume this transformation was probably not seen, as Chan et al concluded that this curious spindle cell component was reactive and nonneoplastic.

In contrast to the report by Chan et al,2 Vergilio and coworkers3 later described spindle cell metaplasia within either PTC or follicular adenomas. These tumor spindle cells were not pleomorphic; their nuclei ranged from plump to thin and elongated. An important distinction here was that these spindle cells were definitively metaplastic thyroid follicular cells that consistently expressed thyroglobulin. The spindle cell component observed in the unusual thyroid carcinoma reported by Mizukami and colleagues4 appears to be histologically different from the other reports we have cited and might be related to thymic differentiation.

The tumor we describe is unique in that the spindle cell component was low to intermediate grade, and, as in the other reports cited, it bore no resemblance to ATC. The blandness was so impressive that a diagnosis of Riedel struma was suspected on initial biopsy. There are morphologic similarities between this case and the cases reported by Chan et al.2 However, we can firmly conclude that the spindle cells herein are neoplastic, and not reactive, as witnessed by the vascular tumor emboli and this patient's unfortunate death. Unlike the tumors described by Bronner and LiVolsi,1 we found no evidence to classify this tumor as a spindle squamous cell carcinoma. However, the light microscopic and ultrastructural findings do support the concept that these spindle cells are epithelial in nature, having transformed from the PTC.

The differential diagnosis, especially on preoperative cytology or biopsy, includes Riedel struma, desmoid tumor, fibrosarcoma, SETTLE, metastatic sarcoma, spindle cell metaplasia, and spindled variant of medullary carcinoma. Spindle cell metaplasia can be easily excluded, as it is the only listed lesion in which the spindle cells consistently and strongly express thyroglobulin. Likewise, a variant of medullary carcinoma can be ruled out by immunohistochemistry for calcitonin. The diagnostician should query as to whether a patient has a clinical history of previous soft tissue sarcoma, as metastasis is always a consideration. It may be impossible to distinguish among the remaining entities on limited preoperative samples.

In conclusion, we report an unusual spindle cell transformation of PTC, which was histologically distinct from ATC. We conclude that this case is related to the peculiar, rare, spindle cell transformations of PTC reported by Bronner and LiVolsi1 and Chan et al,2 and should be regarded as a potentially lethal variant of PTC. Obviously, greater reported experience with similar tumors is necessary to further our understanding, facilitate diagnosis, and enhance our ability to prognosticate.