今日の臨床サポート

乳腺線維腺腫

著者: 小島康幸 聖マリアンナ医科大学 乳腺・内分泌外科

著者: 津川浩一郎 聖マリアンナ医科大学 乳腺・内分泌外科

監修: 中村清吾 昭和大学医学部外科学講座乳腺外科学部門

著者校正済:2022/08/17
現在監修レビュー中
参考ガイドライン:
  1. 日本乳腺甲状腺超音波医学会: 乳房超音波診断ガイドライン 第4版
  1. (公社)日本医学放射線学会(公社)日本放射線技術学会編:マンモグラフィガイドライン 第4版 
  1. 日本乳癌学会:乳癌診療ガイドライン 2022年版
患者向け説明資料
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、 著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※同効薬・小児・妊娠および授乳中の注意事項等は、海外の情報も掲載しており、日本の医療事情に適応しない場合があります。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適応の査定において保険適応及び保険適応外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適応の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
小島康幸 : 特に申告事項無し[2022年]
津川浩一郎 : 未申告[2022年]
監修:中村清吾 : 講演料(第一三共,中外製薬,メディコン),研究費・助成金など(アストラゼネカ,協和キリン,第一三共,島津製作所,大鵬薬品工業,日本化薬,持田製薬),奨学(奨励)寄付など(エーザイ,コニカミノルタ,中外製薬)[2022年]

改訂のポイント:
  1. 乳癌診療ガイドライン2022年版に基づき、レビューを行った。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 線維腺腫は日常診療でしばしば遭遇する乳房腫瘤である。好発年齢は15~35歳といわれ、30歳以下で発見されることが多く、妊娠やエストロゲン補充療法で大きさの増大を認めることがあるが、閉経後は自然退縮するのが一般的である。
  1. 20~30歳代で発見される典型的な乳腺腫瘤の代表として線維腺腫が挙げられる。一方、臨床では閉経年齢以上の方にでも線維腺腫を考える乳房腫瘤を認めることがある。閉経後に線維腺腫が増大することはまれであり、より積極的に癌との鑑別を行う必要がある。
  1. 線維腺腫が癌のrisk factorとする記載もあるが、線維腺腫が癌化する事はきわめてまれで、たまたま線維腺腫に癌が併存したと考えられる。Noguchiらは線維腺腫のclone解析の結果、乳管上皮と間質細胞の過形成によって発生すると説明している[1]
  1. 多くは孤発性で1~2cmの腫瘤として認められ、3cm程度で増大が止まることが多い。10cm以上の巨大線維腺腫が若年に認められることがあり、若年性線維腺腫ともいわれ、頻度は線維腺腫の0.5~2%と報告されている[2][3]
問診・診察のポイント  
  1. 腫瘤の発見時期、大きさとその変化、疼痛の有無、外傷の有無、ホルモン補充療法を受けていないか、月経周期と腫瘤の大きさの変化に関連がないかを確認する。

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文献 

S Noguchi, H Yokouchi, T Aihara, K Motomura, H Inaji, S Imaoka, H Koyama
Progression of fibroadenoma to phyllodes tumor demonstrated by clonal analysis.
Cancer. 1995 Nov 15;76(10):1779-85.
Abstract/Text BACKGROUND: The histogeneses of fibroadenoma and phyllodes tumor of the breast appear to be closely related, but it is still unclear whether fibroadenoma can progress directly to phyllodes tumor.
METHODS: This issue was studied by conducting clonal analysis of fibroadenoma and phyllodes tumors that were obtained sequentially from the same patient. One patient developed local recurrence of phyllodes tumor twice, and the other two patients each developed a phyllodes tumor after excision of a primary fibroadenoma. The method for clonal analysis was based on trinucleotide repeat polymorphism of the X chromosome-linked androgen receptor (AR) gene and on random inactivation of the gene by methylation.
RESULTS: Clonal analysis revealed that all the three primary fibroadenomas were monoclonal and all four recurrent phyllodes tumors were also monoclonal in origin. In addition, the same allele of the AR gene was inactivated in fibroadenoma and phyllodes tumor(s) in each patient. The probability that phyllodes tumors of different origin happen to inactivate the same allele of the AR gene as fibroadenomas in every case is quite low. Rather, it is more reasonable to assume that the phyllodes tumor has the same origin as fibroadenoma.
CONCLUSIONS: These results identified monoclonal fibroadenomas that can progress to phyllodes tumors.

PMID 8625047
Christopher A Park, Lisa R David, Louis C Argenta
Breast asymmetry: presentation of a giant fibroadenoma.
Breast J. 2006 Sep-Oct;12(5):451-61. doi: 10.1111/j.1075-122X.2006.00303.x.
Abstract/Text Patients often present to plastic surgeons with breast asymmetry of unknown etiology. Many patients are females in late adolescence and present complaining of a hypoplastic breast on the smaller side. However, full evaluation may reveal that the larger breast contains the abnormality. Fibroadenomas typically present as firm, mobile, painless, easily palpable breast nodules. However, giant fibroadenomas can present as unilateral macromastia without definable borders or texture differences. Diagnosis is essential since fibroadenomas tend to persist and grow. However, physical examination and standard radiographic evaluations (mammograms and ultrasounds) fail to clarify the diagnosis in many cases. Magnetic resonance imaging (MRI) has improved preoperative diagnosis, but tissue diagnosis is frequently necessary and resection of giant fibroadenomas is essential as they enlarge to the point of causing psychological detriment or mass effects, including venous congestion, glandular distortion, pressure necrosis, and occasionally ulceration. In this article we review nine patients presenting with unilateral macromastia to a tertiary breast care center with a review of the pertinent literature. The differential diagnosis, evaluation modalities, and treatment options of breast asymmetry and unilateral breast masses are presented. Postexcision breast reconstruction is discussed.

PMID 16958965
O Kenneth Macdonald, Christopher M Lee, Jonathan D Tward, Craig D Chappel, David K Gaffney
Malignant phyllodes tumor of the female breast: association of primary therapy with cause-specific survival from the Surveillance, Epidemiology, and End Results (SEER) program.
Cancer. 2006 Nov 1;107(9):2127-33. doi: 10.1002/cncr.22228.
Abstract/Text BACKGROUND: Malignant phyllodes tumor is a rare and potentially aggressive breast neoplasm. Little information is available regarding the optimal management of these lesions and rarer still are data regarding survival. The current study used a large population database to determine prognostic factors that predict cause-specific survival (CSS).
METHODS: Data were obtained from the Surveillance, Epidemiology, and End Results Program (SEER) for the years 1983-2002. Women receiving resection for primary nonmetastatic malignant phyllodes tumor of the breast were included (n = 821). Analyses of patient, pathologic, and treatment characteristics were performed using univariate and multivariate Cox regression analyses for the CSS endpoint.
RESULTS: With a median follow-up of 5.7 years, CSS was 91%, 89%, and 89%, at 5, 10, and 15 years, respectively. Mastectomy was performed in 428 women (52%) and wide excision or lumpectomy in 393 (48%). Women undergoing mastectomy were significantly older (P = .004) and had larger tumors (P = .009). Wide excision was associated with equivalent or improved CSS relative to mastectomy on univariate and multivariate analyses. Older age predicted for cause-specific mortality on multivariate analysis. Adjuvant radiotherapy (RT) predicted for worse CSS when implemented compared with surgery alone.
CONCLUSIONS: Mastectomy was not found to provide a benefit in CSS compared with wide excision in malignant phyllodes tumor of the breast. Women undergoing wide excision had at the minimum similar cancer-specific mortality compared with those who received mastectomy. The role of adjuvant RT is uncertain and requires further investigation.

(c) 2006 American Cancer Society.
PMID 16998937
M Reinfuss, J Mituś, K Duda, A Stelmach, J Ryś, K Smolak
The treatment and prognosis of patients with phyllodes tumor of the breast: an analysis of 170 cases.
Cancer. 1996 Mar 1;77(5):910-6.
Abstract/Text BACKGROUND: The study addresses the controversial prognostic and therapeutic aspects of phyllodes tumor of the breast.
METHODS: Records of 170 women with phyllodes tumor of the breast were reviewed. On the basis of the criteria proposed by Azzopardi and Salvadori et al., including estimation of tumor margin, growth of the connective tissue component, mitoses, and cellular atypia, the entire series was divided into three histotypes of phyllodes tumor, i.e., benign (92 cases, 54.1%), borderline (19 cases, 11.2%), and malignant (59 cases, 34.7%). Ninety-eight patients (57.6%) were treated by wide local excision (79 benign, 15 borderline, and 4 malignant), 43 (25.3%) by simple mastectomy (13 benign, 4 borderline, and 26 malignant), and 29 (17.1%) by radical mastectomy (all malignant).
RESULTS: Of the 170 treated patients, 141 (82.9%) survived 5 years without evidence of disease. In the Cox multivariate analysis the histotype of the tumor was the only independent prognostic factor: 5-year NED survival was observed in 95.7% of the patients with benign phyllodes tumor, 73.7% with borderline phyllodes tumor, and 66.1% with malignant phyllodes tumor. After a wide local excision 98.7% of the patients with benign tumor, and 80% with borderline tumor, were cured. Local recurrence was found in 14 patients (8.2%) (4 benign, 3 borderline, and 7 malignant); 10 of these underwent reoperation (7 wide local excision, 3 radical mastectomy) and survived 5 years NED.
CONCLUSIONS: The histotype of phyllodes tumor (benign, borderline, and malignant), assessed on the basis of the criteria proposed by Azzopardi and Salvadori et al., was the only prognostic factor in our group of patients. Based on the data from literature and our own observations, we observed that a wide local excision, with an adequate margin of normal breast tissue, is the preferred initial therapy for phyllodes tumor of the breast.

PMID 8608483
Simone Schrading, Christiane K Kuhl
Mammographic, US, and MR imaging phenotypes of familial breast cancer.
Radiology. 2008 Jan;246(1):58-70. doi: 10.1148/radiol.2461062173.
Abstract/Text PURPOSE: To prospectively investigate the imaging (mammographic, ultrasonographic [US], magnetic resonance [MR] imaging) features of invasive and intraductal breast cancers in women at familial risk.
MATERIALS AND METHODS: Ethics committee approval and informed consent were obtained. Breast cancers were identified in women at moderately increased risk, in women at high familial risk, and in documented BRCA1 and BRCA2 mutation carriers. All cancers were investigated with mammography, US, and bilateral dynamic breast MR imaging. Imaging findings of breast cancer in women in the different risk categories were prospectively collected and compared. With the two-sample Wilcoxon signed rank test, imaging features of cancers were compared.
RESULTS: Seventy-six breast cancers were identified in 68 women (mean age, 41.3 years). Mammographic breast density had no influence on detectability of cancers. Imaging phenotypes differed among risk categories: 15 (23%) of 64 invasive cancers appeared as fibroadenoma-like masses without calcifications but without fibroadenoma-like internal enhancement or enhancement kinetics at breast MR imaging. Of those, 12 (80%) occurred in women at high risk and documented BRCA1 mutation carriers. A posterior (immediately prepectoral) location was observed in 67% (32 of 48) of all breast cancers in women at high risk and mutation carriers (P < .009). None of the remaining BRCA1-associated invasive cancers exhibited calcifications; intraductal cancers were not observed. In 28 cancers in BRCA2 carriers or women at moderately increased risk, imaging features seemed equivalent to those reported for sporadic cancers; cases of ductal carcinoma in situ were observed, and there was no preference for a posterior location in the breast. At MR imaging, a high percentage (20% [13 of 64]) of invasive cancers appeared as non-masslike enhancement; benign kinetic features were observed in 33% (25 of 76).
CONCLUSION: Imaging phenotypes of cancers differ among risk categories. If MR imaging is used for screening, high sensitivity rates are achievable only if morphologic and kinetic features are assessed and if non-masslike enhancement is considered. Lesion location is important in regard to malignancy.
SUPPLEMENTAL MATERIAL: http://radiology.rsnajnls.org/cgi/content/full/246/1/58/DC1.

RSNA, 2008
PMID 18096529
Su Min Ha, Eun Young Chae, Joo Hee Cha, Hak Hee Kim, Hee Jung Shin, Woo Jung Choi
Association of BRCA Mutation Types, Imaging Features, and Pathologic Findings in Patients With Breast Cancer With BRCA1 and BRCA2 Mutations.
AJR Am J Roentgenol. 2017 Oct;209(4):920-928. doi: 10.2214/AJR.16.16957. Epub 2017 Aug 10.
Abstract/Text OBJECTIVE: The purpose of this study is to retrospectively evaluate the relationships between the BRCA mutation types, imaging features, and pathologic findings of breast cancers in BRCA1 and BRCA2 mutation carriers.
MATERIALS AND METHODS: We identified patients with breast cancer with BRCA gene mutations from January 2000 to December 2014. After excluding patients who underwent lesion excision before MRI, 99 BRCA1 and 103 BRCA2 lesions in 187 women (mean age, 39.7 and 40.4 years, respectively) were enrolled. Mammographic, sonographic, and MRI scans were reviewed according to the BI-RADS lexicon (5th edition). Pathologic data were reviewed, including the immunohistochemistry findings. The relationships between the BRCA mutations and both imaging and pathologic findings were analyzed.
RESULTS: The distribution of molecular subtypes of tumors significantly differed by the mutation type. BRCA1 tumors were associated with the triple-negative subtype, whereas BRCA2 tumors were associated with the luminal B subtype (p = 0.002). At MRI, breast cancers with BRCA1 mutations exhibited a circumscribed margin (p = 0.032) and rim enhancement (p = 0.013). No significant differences in mass shape or kinetic features were observed at MRI. Cancers in BRCA1 mutation carriers tended to develop in the posterior location in the breast (p = 0.034). At mammography, no significant difference in the prevalence of calcifications was observed according to the mutation type. At sonography, BRCA1 lesions were found to be associated with posterior acoustic enhancement (p < 0.0001).
CONCLUSION: Breast cancers with BRCA1 mutations tend to exhibit benign morphologic features at MRI, mammography, and sonography, compared with BRCA2 mutations. Lesion location may represent another difference on imaging among various genetic phenotypes.

PMID 28796549

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