Case Report. Two Cases of Ductal Adenoma of the Breast. Case Report
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1 Breast Cancer Vol. 13 No. 4 October 2006 Case Report Two Cases of Ductal Adenoma of the Breast Ken-ichi Okada 1, Yasuhiro Suzuki 1, Yuki Saito 1, Shinobu Umemura 2, and Yutaka Tokuda 1 1 Department of Surgery and 2 Department of Pathology, Tokai University School of Meidicine, Japan. We encountered two cases of ductal adenoma of the breast. In the first case, a 32-year-old woman presented with a two-year history of a left breast lump. Previous ultrasonography had demonstrated three tumors which were thought to be most likely fibroadenoma. On excisional biopsy of the largest, intraoperative pathological examination of frozen sections was suspicious for ductal carcinoma with a differential diagnosis of intraductal papilloma or intraductal papillary carcinoma. Ductal adenoma was diagnosed after pathological examination of the permanent sections. The second case was a 64-year-old woman who presented with a hard lump in her left breast. Mammography and ultrasonography demonstrated images typical of carcinoma. Aspiration biopsy cytology (ABC) repeated twice was reported as indeterminate. Excisional biopsy was later done. Ductal adenoma (sclerosing papilloma) with hemorrhagic infarction was diagnosed. It is noteworthy that ductal adenoma have clinical and histopathological features that should be differentiated from carcinoma, especially when the tumor is accompanied by secondary changes such as hemorrhage or infarction. Breast Cancer 13: , Key words: Ductal adenoma, Breast, Infarction The term of ductal adenoma has been recently introduced to describe a solid benign lesion of breast ducts 1). The epithelial component of ductal adenomas and nipple adenomas resembles sclerosing adenosis. Previous papers have noted that sclerosing adenosis may contribute to the pathogenesis of both lesions, although these tumors may evolve from sclerotic intraductal papillomas 2-4). These days, sclerotic intraductal papilloma with pronounced adenomatous features tends to be classified in another histological category as ductal adenoma 4). Since ductal adenoma is an uncommon breast lesion that can histologically and clinically mimic carcinoma, surgeons and pathologists should familiarize themselves with this lesion so that patients do not have to undergo unnecessary surgery. We present here two cases of ductal adenoma, a typical case and another case which was Reprint requests to Yasuhiro Suzuki, Department of Surgery, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa , Japan. luke-szk@is.icc.u-tokai.ac.jp Abbreviations: ABC, Aspiration biopsy cytology; MMG, Mammography; US, Ultrasonography Received November 16, 2005; accepted August 4, 2006 diagnositically challenging because of infarction. Case Report We report two cases of ductal adenoma in 32- and 64-year-old Japanese women, who both presented at our hospital with breast tumors which were thought to be malignant on previous clinic visits. The first case, a 32-year-old woman, presented with a two-year history of left breast lump. She complains of abnormal nipple discharge and described the tumor as painful only during menstruation. Physical examination revealed a hard mass, mm with a smooth surface, located in the upper inner quadrant of the left breast. There was serosanguinous discharge from the left nipple. No skin changes or dimpling were seen. Mammography (MMG) demonstrated an oval, well-defined dense mass shadow with microcalcifications in the left breast and was judged category 4 (Fig 1a). Ultrasonography (US) revealed a hypoechoic solid mass mm in diameter, with an irregularly shaped, slightly rough surface. The internal echoes were heterogeneous and accompanied by posterior echoes. Since the mass was connected with a duct, intraductal tumor was sus- 354
2 Breast Cancer Vol. 13 No. 4 October 2006 Fig 1 Mammographic and ultrasonographic appearance and low-power view of ductal adenoma (Case 1). Mammography showed an oval, well-defined dense mass with round calcification (a). Ultrasonography revealed an irregular, hypoechoic solid mass accompanied by duct ectasia (b). Histopathological findings showed an adenomatous nodule surrounded by a densely fibrous ductal wall (c). pected. There were several small strong internal echoes and a cystic part was present around the mass (Fig 1b). Malignancy was assessed based on these findings. Aspiration biopsy cytology (ABC) performed later was reported as normal or benign. In the cystic background, epithelial cell clusters with apocrine metaplasia and stromal elements were identified. Intracystic papilloma was suspected. She underwent excisional biopsy. The tumor was suspected to be ductal carcinoma on intraoperative frozen examination, though examination of permanent sections showed less atypical features. The tumor was mm in size, and was fundamentally an intraductal lesion packed with epithelial cells arranged in a focal papillary fashion (Fig 1c). Florid proliferation of epithelial cells covered the papillae, which had an abundant fibrovascular stromal core. Fibrous scar was identified at the tumor center. Pseudoinvasion, apocrine metaplasia and a pseudocribriform appearance were identified (Fig 2). Particularly, epithelial cells with apocrine features showed increased atypia, enlarged and hyperchromatic nuclei and nuclear pleomorphism. Immunohistochemical studies of Ki-67 and p53 showed no increase, and ductal adenoma was ultimately diagnosed. Epithelial hyperplastic changes extended into the surrounding mammary ducts. The second case was a 64-year-old woman who was found to have a left breast lump comfirmed by US and was to undergo needle biopsy at our hospital. Physical examination revealed a hard and nontender mass, mm, located in the upper external quadrant of her left breast. The tumor was poorly mobile and had an irregular surface. No erythema or skin change, nipple discharge, or dimpling were seen. There was no regional lymphadenopathy. Breast carcinoma was suspected based on these physical findings. All laboratory data were unremarkable. MMG demonstrated a lobulated and well-defined dense mass with a partially unclear boundary and microcalcifications in the left breast (Fig 3a). US revealed a partially irregular and lobulated mass with clear borders mm in diameter. The internal echoic level of the mass was slightly high and heterogeneous and accompanied by posterior echoes. There were several small strong echoes and a small cystic component, The depth to width ratio was low, but no mobility was identified. Mucinous carcinoma was suspected based 355
3 Okada K, et al Ductal Adenoma Accompanied by Infarction Fig 2 Histopathological findings of case 1 revealed a focus of papillary sclerosing adenosis with apocrine metaplasia bulging into the lumen of a large-sized duct (a; hematoxylin-eosin, 2). No malignant cells were identified (b; hematoxylin-eosin, 10). on the echo character (Fig 3b). The results of a repeated ABC were indeterminate. Numerous epithelial cells lacking cohesiveness were obtained. An infarcted lesion was suspected, though the original lesion was not determined. She underwent excisional biopsy at an outpatient clinic. Macroscopically, the cut surface of the submitted tumor showed a well-circumscribed mass with extensive areas brown in color, and a solid part with a whitish-yellow color (Fig 3c, d). Sections of the well-encapsulated tumor showed an intraductal lesion consisting of hyperplastic luminal and myoepithelial components packed in the ductal structure. The epithelial elements were arranged in a tubular, papillary or solid pattern. The central part of the tumor showed extensive infarction with increased fibrous tissue. Pseudoinvasion was focally present at the periphery of the tumor mass. Apocrine metaplasia was occasionally detected. No malignancy was seen. Ductal adenoma (sclerosing papilloma) with hemorrhagic infarction was diagnosed (Fig 3d, 4). There was no evidence of recurrence during follow-up of the two cases. Discussion Ductal adenoma of the breast was described as a benign adenomatoid lesion by Azzopardi and Salm in 1984 and often occurrs in older women 1). It involves small- to medium-sized breast ducts 1), but rarely involves large-sized ducts 2). They rarely exceed 2 cm in greatest dimension. The mean age of the patients in the literature 1) was 51 years. Most cases showed intraductal growth but a fibrotic component sometimes involves the extraductal region, which demonstrates a pseudoinvasive appearance, so it is important to differentiate this lesion from carcinoma. Page and Anderson stated this disease is an undefined disease with mixed characters of sclerosing adenosis, fibroadenoma with ductal structure, and intraductal papilloma in ). It was initially reported as an intraductal adenomatoid sclerotic lesion without papillary or arborescent growth which rarely caused abnormal discharge from the nipple. However in 1989, Lammie and Millis reported it rarely involves large-sized ducts in the subareolar region or presents with abnormal discharge from the nipple, probably due to sclerosis of the intraductal papillary lesion 2). The most characteristic microscopic finding is the circumscription of the lesion with an intermixture of hyalinizing fibrosis and partly attenuated ductal elements in a nodular pattern surrounded by fibrosis 5, 6). The lesional ducts are uniformly lined by epithelial and myoepithelial cells, and have a clearly defined basement membrane that can be visualized with stains for type collagen 7, 8). As in sclerosing adenosis, which demonstrates is extreme attenuation of ducts, only the spindled myoepithelium may be seen and there may be foci of apparent myoepithelial overgrowth 9). Apocrine metaplasia of the ductal epithelium is present in over half of cases and occasional cells with foamy cytoplasm may be seen. Epithelial cells infrequently manifest nuclear pleomorphism and large nucleoli, possibly attributable to apocrine metaplasia 8-11). Microcalcifications are occasionally present and may coalesce to form large densities 4). Ductal adenomas are benign 356
4 Breast Cancer Vol. 13 No. 4 October 2006 Fig 3 Mammographic and ultrasonographic appearance and low-power view of ductal adenoma (Case 2). Mammography showed a lobulated, well-defined dense mass with microcalcification (a). Ultrasonography revealed a partially irregular and lobulated mass with a clear border (b). Histopathological findings showed an adenomatous nodule surrounded by a densely fibrous ductal wall with hemorrhagic infarction (c). Low-power view showed a solid adenomatous growth pattern with hemorrhagic infarction (d). lesions with no tendency for recurrence after complete excision and no evidence of an increased risk of subsequent carcinoma 4). However, since ductal adenoma is an uncommon breast lesion that can histologically and clinically mimic carcinoma, surgeons and pathologists should familiarize themselves with this lesion so that patients do not have to undergo unnecessary oversurgery 11-13). One of our cases (case 1) was a typical ductal adenoma clinically and pathologically. In contrast to case 1, the diagnosis was difficult in case 2 because of secondary changes. It has been reported that infarction can occur in breast lesions especially during pregnancy or lactation 14-16). Fibroadenoma is well known to affect 14, 17) pre-existing tumors, but intraductal papilloma 18), and invasive carcinoma 19) could be similarly affected. In case 2, extensive areas of the tumor had infarcted with a residual ghost-like appearance of the pre-existing structure. As shown in Fig 3c, the tumor mass was surrounded by a thick fibrous capsule packed by solid tumor components. At the periphery of the tumor, narrow slit-like spaces were seen. Viable tumor elements were detectable in a bandlike fashion surrounding the infracted area, which were sufficient for the diagnosis. Invasive carcinoma with infarction was unlikely in this case because the remaining viable cells did not have malignant features. The architectural pattern was also unlikely to be infarcted fibroadenoma. Infarcted 357
5 Okada K, et al Ductal Adenoma Accompanied by Infarction Fig 4 Histopathological findings of case 2. Lower power maginification shows that the tumor is encapsulated by thick fibrous tissue and accompanied by pseudoinvasion. The central area (left upper part) is necrotic with congestive changes. Higher power of magnification shows the tumor mass consists of hyperplastic epithelial elements and occasional apocrine features. (a; hematoxylin-eosin, 2) (b; hematoxylin-eosin, 10). papilloma should be differentiated in this case. Although it is difficult to determine definitively, the characteristics of this tumor, namely the packed growth pattern and predominant tubular rather than papillary structure, and given that the pathological entity of ductal adenoma is indistinguishable from sclerosing papilloma, ductal adenoma with infarction was the most suitable pathological diagnosis for this lesion. In the aspirated material, numerous epithelial cells lacking cohesiveness were obtained. In cases of an infarcted lesion, aspiration cytology can easily yield interminate, results even if viable cells appear to be benign. Thus, even when clinical features, physical examination, mammography and ultrasound suggest malignancy, care must be taken to avoid overdiagnosis and overtreatment. In conclusion, we presented two cases of ductal adenoma, one of which was accompanied by infarction. Overdiagnosis and overtreatment should be avoided in such cases. Acknowledgement The authors wish to thank Dr Johbu Itoh, division of cell science, teaching and research support center, Tokai University School of Medicine, for his technical assistance. References 1) Azzopardi JG, Salm R: Ductal adenoma of the breast: a lesion which can mimic carcinoma. J Pathol 144:15-23, ) Lammie GA, Millis RR: Ductal adenoma of the breast a review of fifteen cases. Hum Pathol 20: , ) Page DL, Anderson TJ: Papilloma and related lesions. Diagnostic Histopathology of the Breast. Churchill Livingstone, Edinburgh, Scottland, pp , ) Rosen PP, Oberman HO: Ductal Adenoma. In Rosen PP, Overman HA eds, Tumors of Mammary Gland. Atlas of Tumor Pathology. Armed Forces Institute of Pathology, Washington, DC, pp69-71, ) Jensen ML, Johansen P, Noer H, Sorensen IM: Ductal adenoma of the breast: the cytological features of six cases. Diagn Cytopathol 10: , ) Kato N, Ohe S, Motoyama T: Ductal adenoma of the breast with chondromyxoid change. Pathol Int 52: , ) Guarino M, Reale D, Squillaci S, Micoli G: Ductal adenoma of the breast. An immunohistochemical study of five cases. Pathol Res Pract 189: , ) Gusterson BA, Sloane JP, Middwood C, Gusterson BA, Gazet JC, Trott P, Taylor-Papadimitriou J, Bartek J: Ductal adenoma of the breast a lesion exhibiting a myoepithelial/epithelial phenotype. Histopathology 11: , ) Moskovic E, Ramachandra S: Ductal adenoma of the breast mammographic appearances and pathological correlation. Br J Radiol 62: , ) Williamson ME, Stock D, Sheridan WG: Fungating benign ductal adenoma of the breast. Br J Surg 80:456, ) Mesonero CE, Tabbara S: Fine-needle aspiration cytology of ductal adenoma: report of a case associated with a mucocele-like lesion. Diagn Cytopathol 13: , ) Carney JA, Toorkey BC: Ductal adenoma of the breast with tubular features. A probable component of the complex of myxomas, spotty pigmentation, endocrine overactivity, and schwannomas. Am J Surg Pathol 15: , ) O Brien SE, Kay JM, Chen VS: Ductal adenoma of the breast. Can J Surg 33: , ) Kim S, Hirai T, Kouro T, Okazaki M, Izawa H, Nishihara M, Ebisui C, Kanai T, Fujimoto T: Two excised cases of infarction of mammary fibroadenoma in lac- 358
6 Breast Cancer Vol. 13 No. 4 October 2006 tation. Jpn J Breast Cancer 15: , ) Pambakian H, Tighe JR: Mammary infarction. Brit J Surg 58: , ) Hasson J, Pope CH: Mammary infarcts associated with pregnancy presenting as breast tumors. Surgery 49: , ) Deshpande KM, Deshpande AH, Raut WK, Lele VR, Bobhate SK: Diagnostic difficulties in spontaneous infarction of a fibroadenoma in an adolescent. Diagn Cytopathol 26:26-28, ) Greenberg ML, Middleton PD, Bilous AM: Infarcted intraductal papilloma diagnosed by fine-needle biopsy. A cytologic, clinical and mammographic pitfall. Diagn Cytopathol 11: , ) Kato N, Itoh H, Matsui N, Miyajima Y, Yasuda M, Umemura S, Osamura RY: A case of invasive ductal carcinoma with extensive infarction of the breast. J Jpn Soc Clin Cytol 42: ,
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