Low-grade Adenosquamous Carcinoma Coexisting with Sclerosing Adenosis of the Breast: A Case Report
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1 31 Case Report J. St. Marianna Univ. Vol. 8, pp , 2017 Low-grade Adenosquamous Carcinoma Coexisting with Sclerosing Adenosis of the Breast: A Case Report Ryoko Oi 1, 2, Ichiro Maeda 1, Yoshio Aida 3, Yukari Yabuki 4, Toru Nishikawa 5, Yoshihide Kanemaki 6, Koichiro Tsugawa 2, and Masayuki Takagi 1 (Received for Publication: January 27, 2017) Abstract Metaplastic carcinoma accounts for only 1% of all breast cancer. Low-grade adenosquamous carcinoma (LGASCa) of the breast belongs to the family of metaplastic carcinomas. Here, we report on a case of LGASCa coexisting with sclerosing adenosis (SA). The patient was a 66-year-old woman. Eight years previously, she had an excisional breast biopsy in a hospital and was diagnosed with SA of her left breast. Three years ago, she presented to our hospital with deformity of the left nipple. We performed a core needle biopsy (CNB) and diagnosed SA. One year ago, a rebiopsy by CNB was performed because of the appearance of cysts in her left breast and worsening of the deformity of the left nipple. The diagnosis of the CNB was SA again. A third CNB was performed 4 months ago because the physical findings suggested malignancy; however, the CNB specimen was diagnosed as SA again. We decided to perform total mastectomy for the final diagnosis. Gross examination of the mastectomy material showed multiple cysts, the largest of which measured cm. Histologically, the tumor was an irregularly shaped mass with duct proliferation and multiple cysts. The infiltrating tumor cells were scattered at the tumor periphery, and some infiltrating tumor cells resembled squamous cells. The tumor cells consisted of two types: one cell type was immunopositive for cytokeratin(ck)14 and p63, and the other cell type was immunopositive for CK14 and immunonegative for p63. Based on the histological and immunohistochemical findings, the diagnosis was LGASCa coexisting with SA and multiple cysts of the breast. Key words Low-grade adenosquamous carcinoma, sclerosing adenosis, p63, CK14, breast Introduction Metaplastic carcinoma accounts for only 1% of all breast cancer. Low-grade adenosquamous carcinoma (LGASCa) of the breast belongs to the family of metaplastic carcinoma. We herein describe a case of LGASCa coexisting with sclerosing adenosis (SA), and multiple cysts, which is an extremely rare occurrence. Case Report Patient The patient was a 66-year-old woman. Clinical course Eight years previously, the patient had an excisional breast biopsy in a hospital and was diagnosed 1 Department of Pathology, St. Marianna University School of Medicine, Kawasaki, Japan 2 Divison of Breast and Endocrine Surgery, Department of Surgery, St. Marianna University School of Medicine, Kawasaki, Japan 3 Department of Pathology, St. Marianna University School of Medicine, Yokohama City Seibu Hospital, Japan 4 Department of Gastroenterological and General Surgery, St. Marianna University School of Medicine, Yokohama City Seibu Hospital, Japan 5 Department of Surgery, Showa University Northern Yokohama Hospital, Japan 6 Department of Radiology, St. Marianna University School of Medicine, Kawasaki, Japan 31
2 32 Oi R Maeda I et al with SA of her left breast. Three years ago, she presented to our hospital with a deformity of the left nipple, and a core needle biopsy (CNB) was performed in our hospital. We diagnosed SA, and the patient returned for a follow-up examination. One year ago, a rebiopsy by CNB was performed because of the appearance of cysts in her left breast and worsened deformity of the left nipple. The diagnosis based on the CNB was again SA. Four months ago, a third CNB was performed because the physical findings suggested malignancy. However, the diagnosis based on the CNB specimen was again SA. We decided to perform a total mastectomy for the final diagnosis because her physical findings could not rule out malignancy. Medical history The patient s medical history included intraductal papilloma of the right breast and angina. Family history The patient had no family history of breast cancer or ovarian cancer. Physical findings A cyst measuring 4 cm in diameter in the left inner upper portion and deformity of the left nipple were found (Fig. 1). Ultrasonography findings of the left breast Three years ago, a hypoechoic lesion measuring 2.0 cm in diameter and without blood flow was found under the left nipple and was suggestive of a benign tumor (Fig. 2a). One year ago, a hypoechoic lesion measuring cm and without blood flow was found in the upper portion of the breast, and two cysts were detected in the vicinity of the hypoechoic lesion. These, too, were suggestive of a benign tumor (Fig. 1b, 1c). Magnetic resonance imaging (MRI) findings of the left breast One year ago, multiple cysts and irregular margins with spiculated enhancement were detected by MRI. These were considered benign tumors caused by inflammatory cell infiltration rather than malignant tumors (Fig. 1d). Fig. 1 Physical findings, ultrasound (US) and magnetic resonance imaging (MRI) 1 year ago. A cystic tumor measuring 4 cm in diameter in the left inner upper portion and a deformity of the left nipple were found. (b, c) US showed hypoechoic cysts and that the hypoechoic lesion measuring cm and without blood flow was increased in the upper portion of the breast. Some cysts were detected in the vicinity of the hypoechoic lesion, which suggested a benign tumor. MRI showed multiple cysts with irregular margins with speculated enhancement, suggesting a benign tumor or inflammatory cell infiltration rather than a malignant tumor. 32
3 Low-grade Adenosquamous Carcinoma. 33 Fig. 2 Ultrasound and histological findings of the CNB specimen obtained 3 years ago. Ultrasonography showed a hypoechoic lesion measuring 2.0 cm in diameter and without blood flow under the nipple of the left breast, which suggested a benign tumor. In the CNB specimen (hematoxylin and eosin (HE) staining, 10), proliferation of small glands and stromal cells was seen, suggesting SA on the right side and hyalinized stroma on the left side. High-power view of Fig. 2b (HE staining, 400) showed numerous ducts comprising proliferative lobules and hyalinized stroma, which are indicative of SA. Immunohistochemistry for p63 showed immunopositive cells around the ducts. Histopathological findings of the left breast Three years ago, the first CNB specimen showed hyalinized stroma and an increased number of small glands and stromal cells (Fig. 2b, 2c); some of the myoepithelial cells were immunopositive for p63 (Fig. 2d). One year ago, the second CNB specimen showed inflammatory cell infiltrates in part of the cystic wall and stroma. Some myoepithelial cells around atrophic tubules were immunopositive for CK14 and p63. These findings suggested SA. Four months ago, the third CNB specimen showed a marked increase in the number of stromal cells, inflammatory cell infiltration, and atypical cells with enlarged nuclei. Mastectomy specime Gross examination showed a mass with multiple cysts, the largest of which measured cm (Fig. 3a). Histologically, the tumor was an irregularly shaped mass lesion with ductal proliferation and multiple small cysts (Fig. 3b). The tumor comprised numerous tubular structures, which indicated SA. In the SA tissue, tubular structures were seen with atypical cells suggestive of flat epithelial atypia and ductal carcinoma in situ components (Fig. 3c and 3d). These lesions contained myoepithelial cells that were immunopositive for p63 and CD10. The infiltrating tumor cells were scattered around the tumor (Fig. 3g), and some of the infiltrating tumor cells resembled squamous cells (Fig. 3h). The tumor cells were immunopositive for the estrogen receptor (ER) and CK14, and some were immunopositive for p63 whereas others were immunonegative for p63 (Fig. 3i). Based on the histological and immunohistochemical findings, LGASCa coexisting with SA and multiple cysts of the breast was diagnosed. Discussion The World Health Organization classified LGASCa under metaplastic carcinoma in LGASCa is characterized by local recurrence, but metastases are rare and patients have an overall good prognosis 1). Grossly, the tumors have irregular outlines with ill-defined borders, with a white or pale yellow cut surface 2). Histologically, they show well- 33
4 Oi R Maeda I et al 34 (e) (f) (g) (h) (i) Fig. 3 Mastectomy specimen. Gross examination of the mass. Multiple cysts were found, the largest of which measured cm. Hematoxylin and eosin (HE) stain ing ( 1) showed a tumor as an irregularly shaped mass with ductal proliferation and multiple cysts. Sclerosing adenosis (SA) and flat epithelial atypia (FEA) (HE stain ing, 200) showed that the tumor comprised numerous tubular structures suggestive of SA (lower portion). In the part containing SA (upper portion), tubular structures with atypical cells indicating FEA were found. FEA (HE staining, 400) shown in a highpower view of Fig 3c with ducts comprising tall columnar cells with atypia. (e and f) Ductal carcinoma in situ (DCIS) in SA (HE staining, 200 and 400) shows epithelial proliferation and cribriform structure suggestive of DCIS and SA. (g) Infiltrating carci noma (HE staining 400) showed infiltrating cancer cell nests with eosinophilic cyto plasm and pleomorphic nuclei. (h) Squamous cancer cells (HE staining, 400) shows squamous cancer cell nests. (i) Infiltrating cancer cell nest (double immunohistochemis try of p63 and CK14) shows two type of cancer cells: one type was immunopositive for p63 and CK14, and the other was immunopositive for CK14 and immunonegative for p63. developed glandular and tubular formation with solid nests of squamous cells1)2). Immunohistochemically, the tumors are immunopositive for high-molecularweight keratins, p63, and smooth muscle actin, and immunonegative for ER, progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2). LGASCa commonly arises within a preex isting radial scar3). Several authors have reported as sociations with fibroadenoma, phyllodes tumor, and ductal carcinoma in situ (DCIS)1 3). Differential diag nosis for LGASCa includes tubular carcinoma, syrin gomatous adenoma of the nipple, and SA. In the breast, the cytoplasm of myoepithelial cells, basal cells, and squamous cells are immunopos itive for CK14, and the nuclei of myoepithelial cells, basal cells, and squamous cells are immunopositive for p63. Numerous cells in benign proliferative le sions are immunopositive for CK14, but malignant cells in the breast are immunegative for CK144). CK14 and p63 double staining showed that the tumor cells comprised two cell types in this patient. One cell type was immunopositive for CK14 and p63, and the other was immunopositive for CK14 and immu nonegative for p63. These results suggested that the tumor cells were basaloid cells or squamous cells rather than myoepithelial cells. Morphologically, there were some squamous cells in this tumor, and we thought that the CK14- and p63-immunopositive 34
5 Low-grade Adenosquamous Carcinoma. 35 cancer cells exhibited squamous changes. SA includes compact proliferation of acinar structures in the peripheral myoepithelial cell layers and lobulocentric proliferation. In a postmortem study of perimenopausal women, the percentage of women with SA of the breast was 3.1% 5). In women with atypical ductal hyperplasia, 17% of those with SA went on to develop invasive carcinoma compared with 4% of those without SA. SA was associated with DCIS, lobular carcinoma in situ, invasive ductal carcinoma, metaplastic carcinoma, and malignant phyllodes tumor 6)7). Cystic disease of the breast is the most common benign disorder of the breast, and 7 10% of women will have it in their lifetime 8)9). Patients with a solitary cyst have very low risk of breast cancer 9). By contrast, Bundred et. al. reported that women with multiple cysts of the breast are significantly more likely to develop breast cancer than women with a solitary cyst. 9) Histological classifications of breast carcinomas with cystic lesions include invasive carcinoma of no special type, adenoid cystic carcinoma, encapsulated papillary carcinoma, squamous carcinoma, and spindle carcinoma 10). Our patient had a very rare case of LGASCa coexisting with SA and multiple cysts. For proper treatment, pathologists and radiologists, surgeons should share clinical information. References 1) Soo K, Tan PH. Low-grade adenosquamous carcinoma of the breast. J Clin Pathol 2013; 66: ) Cha YJ, Kim GJ, Park BW, Koo JS. Low-grade adenosquamous carcinoma of the breast with diverse expression patterns of myoepithelial cell markers on immunohistochemistry: A case study. Korean J Pathol 2014; 48: ) Kawaguchi K, Shin SJ. Immunohistochemical staining characteristics of low-gradeadenosquamous carcinoma of the breast. Am J Surg Pathol 2012; 36: ) Oana Y, Maeda I, Fukushima M, Tsugawa K, Takagi M. Useful Double Immunostaining with p63 and CK14 in the Differential Diagnosis of IDP and DCIS in Fine Needle Aspiration Cytology of the Breast. J Jap Soci Clin Cytol. 54 (2015) ) Oiwa M, Endo T, Shiraiwa M, Nishida C, Morita T, Sato Y, Hayashi T, Kato A, Ichihara S, Moritani S, Hasegawa M, Shinohara N. A clinical and histopathological study of breast carcinoma with sclerosing adenosis. J Jap Assoc Breast Cancer Screen 2011; 20: ) Tovassoli, F. Pathology of the Breast, 2nd edition (McGraw-Hill, 1991). 7) Oiwa M, Endo T, Ichihara S, Moritani S, Hasegawa M, Iwakoshi A, Sato Y, Morita T, Hayashi T, Kato A. Sclerosing adenosis as a predictor of breast cancer bilaterality and multicentricity. Virchows Archiv 2015; 467: ) Arimura T, Takasaki T. A Case of lntracystic Carcinoma (DCIS) Showing Minimal Differentiation from Simple Cyst. J Jap Assoc Breast Cancer Screen 2012; 21: ) Bundred N J, West R R, Dowd J O, Mansel R E, Hughes L E. Is there an increased risk of breast cancer in women who have had a breast cyst aspirated? Brit J Cancer 1991; 64: ) Athanasiou A, Aubert E, Vincent Salomon A, Tardivon A. Complex cystic breast masses in ultrasound examination. Diagn Interv Imaging 2014; 95:
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