An Additional Case of Breast Tumor Resembling the Tall Cell Variant of Papillary Thyroid Carcinoma

Introduction

A type of breast tumor histopathologically similar to the thyroid carcinoma was described in 2003 by Eusebi et al ¹ and named “Breast tumor resembling the tall cell variant of papillary thyroid carcinoma.” ¹ Since then, to the best of our knowledge, a dozen additional cases have been reported with similar morphological findings characterized by columnar to cuboidal eosinophilic cells with grooved nuclei, variable nuclear clearing, and occasional intranuclear inclusions.^2-6

Here, we describe a singular case of “Breast tumor resembling the tall cell variant of papillary thyroid carcinoma” since, unlike the previous cases reported in the literature, the macroscopic appearance resembled thyroid tissue.

Case Report

A 79-year-old woman presented with retroareolar mass in her right breast and bloody secretion of the nipple. Sonographically, the lesion measured 30 mm in largest diameter and was considered suspicious for malignancy. The cytologic exam of nipple secretion was performed and the specimen showed some papillary clusters without cytologic atipia consistent with intraductal papillary lesion. For these reasons, a wide retroareolar quadrantectomy was performed.

Pathologic Findings

The surgical specimen measured 99 mm in its largest diameter. Grossly, the cut surface showed a multinodular gray-tan translucent area of the 85 mm in diameter (Figure 1), appearance similar to a thyroid parenchyma. The specimens were fixed in 10% formalin, embedded in paraffin wax, and sectioned at 4 µm and stained with hematoxylin and eosin.

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Figure 1.

Cut surface of breast specimen with multinodular translucent area. Note the colloid-like aspect (inset).

Histologically, in all slides, the lesion was composed of cystic spaces containing an amorphous eosinophilic material resembling colloid that also showed scalloped borders (Figure 2A). Only at the periphery of some specimens, the lesion showed some cystic spaces with the basophilic material usually seen in the mammary ducts. At higher magnification, some cystic space (approximately 15% of the lesion) was lined by a proliferation of epithelial cells with a papillary architecture (Figure 2B). On high magnification (Figure 2C and D), the epithelial cells had a columnar configuration with granular eosinophilic cytoplasm, nuclear clearing, some nuclear grooving, and numerous nuclear pseudoinclusions. No psammoma bodies were found. Immunohistochemical studies were performed using the following antibodies: gross cystic disease fluid protein–15 (GCDFP-15, clone 23A3, Leica, Milan, Italy), thyroid transcription factor-1 (TTF1, clone 8G7G3/1, Dako, Glostrup, Denmark), thyroglobulin (clone 1D4, Leica), estrogen receptor (clone 6F11, Leica), progesterone receptor (clone 16, Leica), HER2 protein (hercepTest, Dako), collagene IV (clone PHM-12, Leica), p63 (clone 7JUL, Leica), Caldesmon (h-CALD, Bioptica), and Ki-67 (MIB-1, Dako). The cells were positive for GCDFP-15 (Figure 2E), and negative for TTF-1, thyroglobulin, estrogen receptor, progesterone receptor and HER2. The use of collagene IV, p63, and caldesmon were helpful in highlighting some foci of microinvasion (Figure 3).

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Figure 2.

Histological aspect of the tumor. (A) Low-power appearance of the tumor with cystic spaces filled with eosinophilic colloid-like material. (B) Complex, branching papillae projecting in the cystic spaces. (C, D) Tall cells with granular eosinophilic cytoplasm, nuclear clearing, some nuclear grooving, and nuclear pseudoinclusions. (E) Tumor cells show intense immunoreactivity on GCDFP-15 (gross cystic disease fluid protein–15) staining (A-D, hematoxylin and eosin, original magnification ×1.25, ×10, ×40, ×40, respectively; E, GCDFP-15, original magnification ×40).

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Figure 3.

A small focus of invasive carcinoma without evidence of myoepithelial cells (A, hematoxylin and eosin, original magnification ×10; B, p63, original magnification ×40).

These findings were consistent with a diagnosis of ductal carcinoma in situ with microinvasion and cytoarchitectural features of “Breast tumor resembling the tall cell variant of papillary thyroid carcinoma.”

The patient underwent a mastectomy with axillary dissection that showed 2 foci of ductal carcinoma in situ of low nuclear grade while all 8 lymph nodes were negative for tumor. The patient is currently well without signs of recurrence 18 months after the surgery.

Discussion

Breast tumor resembling the tall cell variant papillary thyroid carcinoma was described for the first time in 2003 by Eusebi et al ¹ as a subtype of papillary breast carcinoma with histological features typically seen in papillary thyroid carcinoma. However, further molecular studies suggested that the mechanism leading to distinct pictures of nuclear in these breast carcinoma may be different from the molecular mechanism leading to these features in papillary thyroid carcinoma since RET/PTC rearrangement and BRAF mutations are absent.^2,4,7 Moreover, the presence of cytoarchitectural features typical of papillary thyroid carcinoma is not limited to this entity, as papillary carcinomas of the breast also display such features to a variable extent. Finally, also the prognosis may be similar to that of classical papillary carcinoma of breast. For all these reasons, some authors ⁵ have recently proposed to use the term “Tall cell variant of papillary breast carcinoma” to eliminate confusion about its association with papillary thyroid carcinoma and simplify the terminology surrounding this rare entity.

Here we presented a singular case of this entity that was microscopically similar to the previous cases described but macroscopically it was different. In fact, all the previous cases appeared macroscopically as solid gray mass, a common macroscopic appearance of breast carcinoma. However, in our case the macroscopic appearance closely resembled a thyroid hyperplastic parenchyma; in fact, it was a brownish translucent multinodular tissue. We think that this aspect is due to exaggerated dilatation of mammary ducts with accumulation of amorphous material and blood. This macroscopic appearance, as well as the microscopic appearance of the follicular-like ducts, is something similar to what some authors described in cystic hypersecretory hyperplasia. ⁸

Microscopically, our case is similar to the previous reported cases: a tumor with a follicular, papillary and cystic architecture composed of cells cuboidal or columnar in shape with nuclear clearing, grooves, and pseudoinclusions. In some cases, psammoma bodies were described. Reported data revealed that the majority of tumors were invasive, while only 2 other cases were microinvasive as was the case mentioned above. All studies reported immunoistochemical results, and in all cases tumor cells were negative for TTF1 and thyroglobulin, 2 markers that together characterize nearly 100% of papillary thyroid carcinoma. On the contrary, a variable expression is reported for GCDFP-15, estrogen, and progesterone receptor.

From a practical standpoint because breast is not an uncommon site for metastasis and about 5% of all such cases are of the thyroid origin, ⁹ it is important to be aware of the existence of mammary tumors that can closely mimic a thyroid tumor representing a dangerous diagnostic pitfall that can also lead to unnecessary clinical investigations.