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research-article2014
IJSXXX10.1177/1066896914536222International Journal of Surgical PathologyColella et al
Case Report
An Additional Case of Breast Tumor Resembling the Tall Cell Variant of Papillary Thyroid Carcinoma
International Journal of Surgical Pathology 2015, Vol. 23(3) 217–220 © The Author(s) 2014 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1066896914536222 ijs.sagepub.com
Renato Colella, MD1, Angela Guerriero, MD1, Michele Giansanti, MD1, Angelo Sidoni, MD1, and Guido Bellezza, MD1
Abstract A type of breast tumor histopathologically similar to the papillary thyroid carcinoma has been described and named “Breast tumor resembling the tall cell variant of papillary thyroid carcinoma.” Because breast is not an uncommon site for metastasis and about 5% of all such cases are of the thyroid origin, 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. Here, we describe a singular case of “Breast tumor resembling the tall cell variant of papillary thyroid carcinoma” showing an amazing macroscopic and microscopic resemblance with thyroid tissue harboring a papillary carcinoma. Keywords breast tumor, tall cell variant, papillary breast carcinoma, papillary thyroid carcinoma
Introduction A type of breast tumor histopathologically similar to the thyroid carcinoma was described in 2003 by Eusebi et al1 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
Figure 1. Cut surface of breast specimen with multinodular translucent area. Note the colloid-like aspect (inset).
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. 1
Department of Experimental Medicine, Section of Pathological Anatomy and Histology, University of Perugia, Perugia, Italy Corresponding Author: Renato Colella, S.C. Anatomia e Istologia Patologica, Azienda, Ospedaliero Universitaria di Perugia, Ospedale S. Maria della Misericordia, Piazzale Menghini 1, I-06132, Perugia, Italy. Email: [email protected]
218 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). 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 al1 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
International Journal of Surgical Pathology 23(3) 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 authors5 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.
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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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International Journal of Surgical Pathology 23(3)
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).
Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.
References 1. Eusebi V, Damiani S, Ellis IO, Azzopardi JG, Rosai J. Breast tumor resembling the tall cell variant of papillary thyroid carcinoma: report of 5 cases. Am J Surg Pathol. 2003;27:1114-1118. 2. Cameselle-Teijeiro J, Abdulkader I, Barreiro-Morandeira F, et al. Breast tumor resembling the tall cell variant of papillary thyroid carcinoma: a case report. Int J Surg Pathol. 2006;14:79-84. 3. Chang SY, Fleiszer DM, Mesurolle B, El Khoury M, Omeroglu A. Breast tumor resembling the tall cell variant of papillary thyroid carcinoma. Breast J. 2009;15:531535.
4. Hameed O, Perry A, Banerjee R, Zhu X, Pfeifer JD. Papillary carcinoma of the breast lacks evidence of RET rearrangements despite morphological similarities to papillary thyroid carcinoma. Mod Pathol. 2009;22:1236-1242. 5. Masood S, Davis C, Kubik MJ. Changing the term “breast tumor resembling the tall cell variant of papillary thyroid carcinoma” to “tall cell variant of papillary breast carcinoma”. Adv Anat Pathol. 2012;19:108-110. 6. Tosi AL, Ragazzi M, Asioli S, et al. Breast tumor resembling the tall cell variant of papillary thyroid carcinoma: report of 4 cases with evidence of malignant potential. Int J Surg Pathol. 2007;15:14-19. 7. Chiang S, Cole K, Baker G, et al. Solid papillary neoplasms with reverse polarization (SPNRPs): histologic, immunophenotypic and genotypic characterization of a distinctive breast tumor. Poster presented at: USCAP 103rd Annual Meeting; March 2-7, 2014; San Diego, CA. 8. Guerry P, Erlandson RA, Rosen PP. Cystic hypersecretory hyperplasia and cystic hypersecretory duct carcinoma of the breast. Pathology, therapy, and follow-up of 39 patients. Cancer. 1988;61:1611-1620. 9. Fiche M, Cassagnau E, Aillet G, et al. Breast metastasis from a “tall cell variant” of papillary thyroid carcinoma [in French]. Ann Pathol. 1998;18:130-132.
Copyright of International Journal of Surgical Pathology is the property of Sage Publications Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
research-article2014
IJSXXX10.1177/1066896914536222International Journal of Surgical PathologyColella et al
Case Report
An Additional Case of Breast Tumor Resembling the Tall Cell Variant of Papillary Thyroid Carcinoma
International Journal of Surgical Pathology 2015, Vol. 23(3) 217–220 © The Author(s) 2014 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1066896914536222 ijs.sagepub.com
Renato Colella, MD1, Angela Guerriero, MD1, Michele Giansanti, MD1, Angelo Sidoni, MD1, and Guido Bellezza, MD1
Abstract A type of breast tumor histopathologically similar to the papillary thyroid carcinoma has been described and named “Breast tumor resembling the tall cell variant of papillary thyroid carcinoma.” Because breast is not an uncommon site for metastasis and about 5% of all such cases are of the thyroid origin, 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. Here, we describe a singular case of “Breast tumor resembling the tall cell variant of papillary thyroid carcinoma” showing an amazing macroscopic and microscopic resemblance with thyroid tissue harboring a papillary carcinoma. Keywords breast tumor, tall cell variant, papillary breast carcinoma, papillary thyroid carcinoma
Introduction A type of breast tumor histopathologically similar to the thyroid carcinoma was described in 2003 by Eusebi et al1 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
Figure 1. Cut surface of breast specimen with multinodular translucent area. Note the colloid-like aspect (inset).
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. 1
Department of Experimental Medicine, Section of Pathological Anatomy and Histology, University of Perugia, Perugia, Italy Corresponding Author: Renato Colella, S.C. Anatomia e Istologia Patologica, Azienda, Ospedaliero Universitaria di Perugia, Ospedale S. Maria della Misericordia, Piazzale Menghini 1, I-06132, Perugia, Italy. Email: [email protected]
218 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). 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 al1 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
International Journal of Surgical Pathology 23(3) 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 authors5 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.
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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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International Journal of Surgical Pathology 23(3)
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).
Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.
References 1. Eusebi V, Damiani S, Ellis IO, Azzopardi JG, Rosai J. Breast tumor resembling the tall cell variant of papillary thyroid carcinoma: report of 5 cases. Am J Surg Pathol. 2003;27:1114-1118. 2. Cameselle-Teijeiro J, Abdulkader I, Barreiro-Morandeira F, et al. Breast tumor resembling the tall cell variant of papillary thyroid carcinoma: a case report. Int J Surg Pathol. 2006;14:79-84. 3. Chang SY, Fleiszer DM, Mesurolle B, El Khoury M, Omeroglu A. Breast tumor resembling the tall cell variant of papillary thyroid carcinoma. Breast J. 2009;15:531535.
4. Hameed O, Perry A, Banerjee R, Zhu X, Pfeifer JD. Papillary carcinoma of the breast lacks evidence of RET rearrangements despite morphological similarities to papillary thyroid carcinoma. Mod Pathol. 2009;22:1236-1242. 5. Masood S, Davis C, Kubik MJ. Changing the term “breast tumor resembling the tall cell variant of papillary thyroid carcinoma” to “tall cell variant of papillary breast carcinoma”. Adv Anat Pathol. 2012;19:108-110. 6. Tosi AL, Ragazzi M, Asioli S, et al. Breast tumor resembling the tall cell variant of papillary thyroid carcinoma: report of 4 cases with evidence of malignant potential. Int J Surg Pathol. 2007;15:14-19. 7. Chiang S, Cole K, Baker G, et al. Solid papillary neoplasms with reverse polarization (SPNRPs): histologic, immunophenotypic and genotypic characterization of a distinctive breast tumor. Poster presented at: USCAP 103rd Annual Meeting; March 2-7, 2014; San Diego, CA. 8. Guerry P, Erlandson RA, Rosen PP. Cystic hypersecretory hyperplasia and cystic hypersecretory duct carcinoma of the breast. Pathology, therapy, and follow-up of 39 patients. Cancer. 1988;61:1611-1620. 9. Fiche M, Cassagnau E, Aillet G, et al. Breast metastasis from a “tall cell variant” of papillary thyroid carcinoma [in French]. Ann Pathol. 1998;18:130-132.
Copyright of International Journal of Surgical Pathology is the property of Sage Publications Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
