BREAST IMAGES
Synchronous Pleomorphic Adenoma and Invasive Ductal Carcinoma in Distinct Breasts Maurizio Di Bonito, MD, Monica Cantile, PhD, Margherita Cerrone, BD, Giuseppina Liguori, BD, and Gerardo Botti, MD Pathology Unit, INT Fondazione Pascale, Naples, Italy
A
58-year-old woman, after a mammography with suspicious findings, was referred to our Institution. The mammography two nodules of about 1 cm revealed in the superior external quadrant of the right breast, one of which also appeared at the ultrasound examination suspicious for malignancy. Core needle biopsy (CNB) revealed the presence of invasive ductal carcinoma with areas of ductal carcinoma in situ (DCIS) of intermediate grade in the suspicious nodule, and areas of DCIS of high grade in the other. Mammography on contralateral breast showed a retro areolar nodule with increased thickness but wellcircumscribed, which was also confirmed at the ultrasound examination. CNB revealed a florid atypical ductal proliferation in a myxoid stroma associated with mucoid-like substance. The patient underwent to definitive surgery for excision of all lesions. For the right bilateral nodules, histologic evaluation confirmed the existence of two lesions, with a distance of 2 cm. The first appeared as an invasive ductal carcinoma with areas of DCIS of intermediate grade, while the second revealed a DCIS of high grade. Immunohistochemical antibodies panel, carried out only on the first nodule, showed a strong positivity for estrogen receptor (ER) (85%), a low expression of progesteron receptor (PgR) (5%), an high proliferation index ki67 and a positivity for V-ERB-B2 AVIAN ERYTHROBLASTIC LEUKEMIA VIRAL ONCOGENE HOMOLOG 2 (HER-2) with a 1+ score FDA (Fig. 1). Further cytogenetic analysis, using the FISH Address correspondence and reprint requests to: Monica Cantile, Pathology Unit, INT Fondazione Pascale, Via M. Semmola, Naples 80131, Italy, or e-mail: [email protected];[email protected] DOI: 10.1111/tbj.12426 © 2015 Wiley Periodicals, Inc., 1075-122X/15 The Breast Journal, Volume 21 Number 4, 2015 428–430
method, did not show any gene amplification of HER2 (Fig. 1). For the left nodule, the histologic evaluation and immunohistochemical antibodies panel showed a focal positivity for ER, negativity for PgR, a low proliferation index ki67 and a positivity for vimentin, pan CK, S100, smooth muscle actin (SMA), and p63 markers (Fig. 2). These findings have raised the problem of differential diagnosis with breast metaplastic carcinoma. However, the morphology and immunoprofile associated with the positivity for ER, negativity for PgR, low proliferative index and low mitotic activity were consistent with a diagnosis of pleomorphic adenoma of breast (PAB). In this report we present for the first time the coexistence of a very rare lesion of the breast, a pleomorphic adenoma, and a ductal carcinoma in distinct breasts. Primary tumors that co-exist at the time of diagnosis are defined “synchronous,” whereas if they gradually develop they are defined as “metachronous.” This condition is quite common for malignant lesions that occur in bilaterally symmetrical organs, such as breasts, kidneys, ovaries, testes, and salivary glands. However, synchronous benign and malign lesions in separate breasts have not been reported. In literature, only one case, showing the presence of a benign phylloides tumor and invasive ductal carcinoma in contralateral breast has been described. Pleomorphic adenoma, a benign mixed tumor, accounts for 50–80% of all salivary gland tumors, but has been reported also in other anatomic sites, such as larynx, palate, but very rarely in breast. Salivary glands and breast are both tubule-acinar exocrine glands and their similarity also accompany
Pleomorphic Adenoma and IDC • 429
(a)
(b)
(c)
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Figure 1. Right breast lesion Immunophenotype: (a) H&E morphology (109), (b) immunopositivity for ER (209), (c) immunopositivity for PgR (209), (d) immunopositivity for Ki67 (209), (e) immunopositivity for HER-2 (209). In the last box on the right, FISH analysis of HER-2 gene without amplification signals.
their pathologic processes of neoplastic transformation. PAB usually affects female patients, and frequently is located in the sub-areolar region of the breast. Morphologically, PAB is characterized by glandular structures, with a luminal layer of epithelial cells surrounded by an outer layer of myoepithelial cells, immersed in a myxoid stroma associated with chondroid and osteoid metaplasia. By immunohistochemistry, the epithelial cells are strongly positive for cytokeratin and epithelial membrane antigen, and occasionally positive for vimentin. Myoepithelial cells are strongly positive for CD10, p63, SMA and cytokeratins. S100 can have a variable expression, but more intense in myoepithelial cells. ER and PgR have a variable positivity. One of the main issues that emerged in this case, but typical of this benign lesion was represented by the
differential diagnosis of PAB with metaplastic carcinoma of breast. This lesion, which accounts for less than 1% of all invasive breast tumors, is characterized by an abundant extracellular matrix with chondroid or osteoid islands. However, metaplastic carcinoma displays generally a negativity for ER and PgR, nuclear atypia, many mitoses and high proliferation index, which are not present in PAB, like in our case. The case described is interesting not only for the rarity of PAB lesion, but also for their association with a malign lesion in controlateral breast. Genetic predisposition to develop multiple cancers is still currently the subject of numerous studies. It was frequently reported that the coexistence of two or more tumors, synchronous or metachronous, in the same patient, may also be correlated with hereditary
430 • di bonito et al.
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(b)
(c)
(d)
(e)
(f)
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Figure 2. Left breast lesion Immunophenotype: (a) H&E morphology (109), (b) immunopositivity for ER (209), (c) immunopositivity for Ki67 (209), (d) immunopositivity for panCK (209), (e) immunopositivity for vimentin (209), (f) immunopositivity for actin (209), (g) immunopositivity for p63 (209), (h) immunopositivity for S100 (209).
syndromes. Our case presented also areas of precursors lesions, such as DCIS, whose molecular alterations represent a crucial point in its tumor progression. Although genetic relation between these lesions were not described, we can speculate that some common biologic characteristics and early genetic
alterations may underlie the synchronous occurrence of these lesions. CONFLICTS OF INTEREST The authors indicated no potential conflicts of interest.
Synchronous Pleomorphic Adenoma and Invasive Ductal Carcinoma in Distinct Breasts Maurizio Di Bonito, MD, Monica Cantile, PhD, Margherita Cerrone, BD, Giuseppina Liguori, BD, and Gerardo Botti, MD Pathology Unit, INT Fondazione Pascale, Naples, Italy
A
58-year-old woman, after a mammography with suspicious findings, was referred to our Institution. The mammography two nodules of about 1 cm revealed in the superior external quadrant of the right breast, one of which also appeared at the ultrasound examination suspicious for malignancy. Core needle biopsy (CNB) revealed the presence of invasive ductal carcinoma with areas of ductal carcinoma in situ (DCIS) of intermediate grade in the suspicious nodule, and areas of DCIS of high grade in the other. Mammography on contralateral breast showed a retro areolar nodule with increased thickness but wellcircumscribed, which was also confirmed at the ultrasound examination. CNB revealed a florid atypical ductal proliferation in a myxoid stroma associated with mucoid-like substance. The patient underwent to definitive surgery for excision of all lesions. For the right bilateral nodules, histologic evaluation confirmed the existence of two lesions, with a distance of 2 cm. The first appeared as an invasive ductal carcinoma with areas of DCIS of intermediate grade, while the second revealed a DCIS of high grade. Immunohistochemical antibodies panel, carried out only on the first nodule, showed a strong positivity for estrogen receptor (ER) (85%), a low expression of progesteron receptor (PgR) (5%), an high proliferation index ki67 and a positivity for V-ERB-B2 AVIAN ERYTHROBLASTIC LEUKEMIA VIRAL ONCOGENE HOMOLOG 2 (HER-2) with a 1+ score FDA (Fig. 1). Further cytogenetic analysis, using the FISH Address correspondence and reprint requests to: Monica Cantile, Pathology Unit, INT Fondazione Pascale, Via M. Semmola, Naples 80131, Italy, or e-mail: [email protected];[email protected] DOI: 10.1111/tbj.12426 © 2015 Wiley Periodicals, Inc., 1075-122X/15 The Breast Journal, Volume 21 Number 4, 2015 428–430
method, did not show any gene amplification of HER2 (Fig. 1). For the left nodule, the histologic evaluation and immunohistochemical antibodies panel showed a focal positivity for ER, negativity for PgR, a low proliferation index ki67 and a positivity for vimentin, pan CK, S100, smooth muscle actin (SMA), and p63 markers (Fig. 2). These findings have raised the problem of differential diagnosis with breast metaplastic carcinoma. However, the morphology and immunoprofile associated with the positivity for ER, negativity for PgR, low proliferative index and low mitotic activity were consistent with a diagnosis of pleomorphic adenoma of breast (PAB). In this report we present for the first time the coexistence of a very rare lesion of the breast, a pleomorphic adenoma, and a ductal carcinoma in distinct breasts. Primary tumors that co-exist at the time of diagnosis are defined “synchronous,” whereas if they gradually develop they are defined as “metachronous.” This condition is quite common for malignant lesions that occur in bilaterally symmetrical organs, such as breasts, kidneys, ovaries, testes, and salivary glands. However, synchronous benign and malign lesions in separate breasts have not been reported. In literature, only one case, showing the presence of a benign phylloides tumor and invasive ductal carcinoma in contralateral breast has been described. Pleomorphic adenoma, a benign mixed tumor, accounts for 50–80% of all salivary gland tumors, but has been reported also in other anatomic sites, such as larynx, palate, but very rarely in breast. Salivary glands and breast are both tubule-acinar exocrine glands and their similarity also accompany
Pleomorphic Adenoma and IDC • 429
(a)
(b)
(c)
(d)
(e)
Figure 1. Right breast lesion Immunophenotype: (a) H&E morphology (109), (b) immunopositivity for ER (209), (c) immunopositivity for PgR (209), (d) immunopositivity for Ki67 (209), (e) immunopositivity for HER-2 (209). In the last box on the right, FISH analysis of HER-2 gene without amplification signals.
their pathologic processes of neoplastic transformation. PAB usually affects female patients, and frequently is located in the sub-areolar region of the breast. Morphologically, PAB is characterized by glandular structures, with a luminal layer of epithelial cells surrounded by an outer layer of myoepithelial cells, immersed in a myxoid stroma associated with chondroid and osteoid metaplasia. By immunohistochemistry, the epithelial cells are strongly positive for cytokeratin and epithelial membrane antigen, and occasionally positive for vimentin. Myoepithelial cells are strongly positive for CD10, p63, SMA and cytokeratins. S100 can have a variable expression, but more intense in myoepithelial cells. ER and PgR have a variable positivity. One of the main issues that emerged in this case, but typical of this benign lesion was represented by the
differential diagnosis of PAB with metaplastic carcinoma of breast. This lesion, which accounts for less than 1% of all invasive breast tumors, is characterized by an abundant extracellular matrix with chondroid or osteoid islands. However, metaplastic carcinoma displays generally a negativity for ER and PgR, nuclear atypia, many mitoses and high proliferation index, which are not present in PAB, like in our case. The case described is interesting not only for the rarity of PAB lesion, but also for their association with a malign lesion in controlateral breast. Genetic predisposition to develop multiple cancers is still currently the subject of numerous studies. It was frequently reported that the coexistence of two or more tumors, synchronous or metachronous, in the same patient, may also be correlated with hereditary
430 • di bonito et al.
(a)
(b)
(c)
(d)
(e)
(f)
(g)
(h)
Figure 2. Left breast lesion Immunophenotype: (a) H&E morphology (109), (b) immunopositivity for ER (209), (c) immunopositivity for Ki67 (209), (d) immunopositivity for panCK (209), (e) immunopositivity for vimentin (209), (f) immunopositivity for actin (209), (g) immunopositivity for p63 (209), (h) immunopositivity for S100 (209).
syndromes. Our case presented also areas of precursors lesions, such as DCIS, whose molecular alterations represent a crucial point in its tumor progression. Although genetic relation between these lesions were not described, we can speculate that some common biologic characteristics and early genetic
alterations may underlie the synchronous occurrence of these lesions. CONFLICTS OF INTEREST The authors indicated no potential conflicts of interest.
