Phyllodes tumor of the breast: stromal overgrowth and histological classification are useful prognosis-predictive factors for local recurrence in patients with a positive surgical margin

BACKGROUND: The local recurrence rate of phyllodes tumors is high and ensuring a sufficient surgical margin is considered important for local control. However, the preoperative diagnosis rate of phyllodes tumors is low and we often encounter cases in which a sufficient surgical margin is not achieved, since in routine medical practice the lesion may not be diagnosed as phyllodes tumor until postoperative biopsy of a mammary mass. Furthermore, there are no established therapeutic guidelines for surgical stump-positive phyllodes tumors. We reviewed the outcomes of excision of phyllodes tumors to investigate factors involved in local recurrence and to determine the indication for re-excision in stump-positive cases. METHODS: The subjects were 45 patients treated for phyllodes tumors at our institution from January 1980 to July 2005. Age, tumor size, surgical method, stromal cellular atypia, mitotic activity, stromal overgrowth, histological classification and surgical stump status were analyzed. RESULTS: Median age was 45 years old (range 28-75) and tumor size was 1-17 cm (median 3.5 cm). Pathologic diagnoses were benign, borderline and malignant in 31, five and nine cases, respectively, and the surgical stump was negative in 27 lesions and positive in 15. Median follow-up was 101 months (range 1-273), with local recurrence in six cases and distant metastasis in one. The local recurrence-free rate was 88, 88 and 84% and the disease-free rate was 85, 85 and 81% after 5, 10 and 15 years, respectively. Overall 10-year survival was 97%. In univariate analysis, a positive surgical margin, stromal overgrowth and histological classification were predictive factors for local recurrence after breast-conservation surgery (P = 0.0034, 0.0003, 0.026). A positive surgical stump was the only independent predictor of local recurrence in multivariate analysis (RR 0.086; 95% CI 0.01-0.743, P = 0.012). Stromal overgrowth was a predictive factor for local recurrence in cases with a positive surgical margin (P = 0.0139). CONCLUSION: Wide excision is the preferred therapy for phyllodes tumor and preoperative diagnosis is important for good local control. Re-excision is recommended in cases with a positive surgical margin and stromal overgrowth and malignancy.     

Long-term results of surgical therapy for phyllodes tumor of the breast

We report that the long-term results of surgical therapy for phyllodes tumor of the breast. During ten years, we experienced twenty-eight patients of phyllodes tumors of the breast. They were treated by surgical operation. Twenty-one cases were performed local excision with at least 1 cm surgical margin, and seven cases were performed muscle preserving mastectomy without axillary lymph nodes dissection. Pathological surgical margins of all patients were negative. Five patients were recognized the local recurrence, and only one patient was recognized a distant metastasis. The total recurrence rate was 21.4%. The patients with local recurrence were diagnosed the benign phyllodes tumor of the breast at the first operation. The mean time to recurrence was 5.4 years. If the pathological diagnosis was benign phyllodes tumor and surgical margin was negative at the first operation, it is necessary to follow up the patients, because there is a risk of local and distant metastasis.     

乳腺叶状肿瘤局部复发的临床风险因素分析

目的分析乳腺叶状肿瘤局部复发的临床风险因素。方法使用SPSSCox比例风险模型分析2002年12月至2008年12月中国医科大学附属第一医院66例乳腺叶状肿瘤患者各种临床风险因素与局部复发的关系。单因素分析采用X2检验。结果本组患者的发病年龄为17—83岁（中位年龄41岁）,良性40例,交界性24例,恶性2例。局部复发15例,其中12例复发发生于区段切除术。在不同手术方式、不同组织学等级的叶状肿瘤患者之间,复发率的差异均有统计学意义（P〈0．05）。手术方式为保护因素（RR=0．151）,扩大切除术和乳房切除术者的复发风险较区段切除术者下降至66／1000和53／1000;组织学等级为危险因素（RR=5．803）,恶性和交界性叶状肿瘤患者的局部复发风险分别为良性肿瘤者的12．26倍和4．37倍。结论恶性程度高和手术方式选择不当影响预后。叶状肿瘤以手术治疗为首选,应选择切除范围扩大的手术方式,尤其是对恶性程度高的患者。     

乳腺叶状肿瘤的诊断及治疗

目的探讨乳腺叶状肿瘤的诊断和治疗.方法对经手术和病理诊断的48例乳腺叶状肿瘤的临床病理资料进行回顾性分析.结果48例中平均年龄为43.2岁.根据肿瘤生长方式,瘤细胞异型,核分裂和肿瘤坏死进行乳腺叶状肿瘤分级,良性26例,交界性12例,恶性10例.全部病例采用手术治疗,肿瘤单纯切除术23例,良性、交界性、恶性复发分别为3/18、2/3、2/2;肿瘤扩大切除术15例,良性、交界性、恶性复发分别为0/8、1/5、1/2;乳房切除术10例,交界性、恶性复发转移分别为0/4、2/6.结论乳腺叶状肿瘤可分良性、交界性和恶性三种类别,确诊和分级主要依靠病理组织检查.提示首次肿瘤彻底切除是治疗的关键,应根据组织分级及肿瘤大小决定手术方式.     

乳腺叶状肿瘤17例诊疗分析

目的:探讨乳腺叶状肿瘤的治疗原则和影响预后因素。方法:对经手术和病理诊断确诊的17例乳腺叶状肿瘤的临床资料进行回顾性分析。结果:17例患者中良性叶状肿瘤9例,交界性叶状肿瘤5例,恶性3例。行局部肿块切除7例,单纯乳房切除术6例,改良根治术3例,姑息性肿块切除术1例。其中随访13例,平均随访时间21(5~84)个月,1例行乳腺癌改良根治术后2.5年死于远处转移,2例行局部肿块切除术后复发。结论:乳腺叶状肿瘤的预后与手术方式有关,良性和交界性应首选扩大区段切除术,切除肿瘤边缘不少于2cm;复发的交界性和恶性应尽早行单纯乳房切除术。     

乳腺叶状肿瘤复发的治疗及预后分析

目的 探讨乳腺叶状肿瘤复发的治疗方法以及预后.方法 回顾分析1972年3月至2006年6月收治的26例乳腺叶状肿瘤复发患者的临床资料.结果 26例患者的中位生存时间为96个月.原发肿瘤≥5 cm者10例,其中6例出现局部复发,4例死亡;<5 cm者16例,其中5例出现局部复发,3例死亡.复发肿瘤≥5 cm者14例,其中5例出现局部复发,3例死亡;<5 cm者12例,其中6例出现局部复发,4例死亡.原发肿瘤和复发肿瘤的大小对肿瘤再次复发(P=0.094,P=0.383)和预后(P=0.142,P=0.486)影响不显著.良性肿瘤组12例患者中,3例出现局部复发,2例死亡;恶性肿瘤组14例患者中,8例小现局部复发,5例死亡.乳腺叶状肿瘤的良恶性与肿瘤再次复发(P=0.046)和预后(P=0.028)存存相关性.结论 乳腺叶状肿瘤的恶性程度对肿瘤再次局部复发和患者预后有显著影响,而肿瘤大小与再次局部复发和预后无关.乳腺叶状肿瘤复发后的补救手术十分重要,手术必须保证一定的安全范围;多次局部复发患者的于术治疗效果较好.     

Primary treatment of cystosarcoma phyllodes of the breast

BACKGROUND: Cystosarcoma phyllodes is a rare sarcoma of the breast. Although surgical removal is the mainstay of treatment, the extent of surgery required (excision vs. mastectomy) and the need for additional local therapy, such as radiotherapy, are unclear. The current study evaluated the rate of local and distant failure, as well as potential prognostic factors, to better define appropriate treatment strategies. METHODS: One hundred one patients treated primarily for cystosarcoma phyllodes of the breast were evaluated. These tumors were classified histologically into benign (58%), indeterminate (12%), and malignant (30%) based on well defined criteria. Stromal overgrowth (29%) was considered separately. Surgery was comprised of local excision with breast conservation (47%) or mastectomy (53%). Microscopic surgical margins were negative in 99% of cases. Six patients received adjuvant radiotherapy. RESULTS: Overall survival for the 101 patients was 88%, 79%, and 62% at 5, 10, and 15 years, respectively. For patients with nonmalignant (benign or indeterminate) and malignant cystosarcoma phyllodes, the overall survival was 91% and 82%, respectively, at 5 years, and 79% and 42%, respectively, at 10 years. Similar rates were observed based on the presence or absence of stromal overgrowth. Local recurrence occurred in 4 patients, with an actuarial 10-year rate of 8%. Eight patients developed distant metastases, with an actuarial 10-year rate of 13%. Multivariate analysis using Cox proportional hazards regression revealed stromal overgrowth to be the only independent predictor of distant failure. CONCLUSIONS: Local failure in this group of largely margin negative patients with cystosarcoma phyllodes of the breast was low, showing that breast-conserving surgery with appropriate margins is the preferred primary therapy. The current study data do not support the use of adjuvant radiotherapy for patients with adequately resected disease. Patients with stromal overgrowth, particularly when the tumor size was > 5 cm, were found to have a high rate of distant failure; such patients merit consideration of a trial that examines the efficacy of systemic therapy.     

Cystosarcoma phyllodes of the breast: a case report in a 12-year-old girl

Breast tumors in adolescents are very rare and mostly benign. Fibroadenomas are the most frequent, but within the extensive differential diagnosis, the phyllodes tumor must be mentioned, which accounts for about 1% of breast tumors and the diagnosis of which is very rare in patients younger than 20 years. There are no specific symptoms or radiological images to distinguish phyllodes tumor from fibroadenoma; therefore, histological examination is mandatory for diagnosis. Histology also allows the classification of phyllodes tumor into benign, borderline, or malignant types for appropriate surgical treatment: freemargin excision in benign tumors and mastectomy in the other two types. Fortunately, the majority of these tumors are benign, and treatment maximizes breast conservation with free infiltration margins surgery, given that this fact is the most important factor to prevent local recurrence. In this article, we describe a rare case of borderline cystosarcoma phyllodes in a 12-year-old girl.     

Histologic features predict local recurrence after breast conserving therapy of phyllodes tumors

Background: Pathologists can distinguish benign phyllodes tumors, which very rarely metastasize, from malignant phyllodes tumors, which metastasize in approximately one fourth of patients. However, whether these same histologic criteria can be used to predict the likelihood that a phyllodes tumor will locally recur after breast conserving therapy remains controversial.Study Design: Since few patients with malignant phyllodes tumors have been treated with breast conserving surgery in any individual series, the literature was reviewed using a Medline search.Results: After local excision, 21 (111/540), 46 (18/39), and 65 (26/40) of patients with benign, borderline, and malignant phyllodes tumors, respectively, recurred in the breast. Following wide local excision, 8 (17/212), 29 (20/68), and 36 (16/45) of patients with benign, borderline, and malignant phyllodes tumors recurred in the breast.Conclusions: Malignant phyllodes tumors are much more likely than benign phyllodes tumors to recur in the breast after breast conserving surgery. This high rate of local recurrence of borderline and malignant phyllodes tumors suggests that wide local excision is less than optimal therapy, and challenges us to look for methods to improve local tumor control.     

Phyllodes tumor of the breast: a multicenter series of 59 cases. Coordinating Center and Writing Committee of FONCAM (National Task Force for Breast Cancer), Italy.

A series of 59 phyllodes tumors of the breast was retrospectively reviewed (average follow-up = 3.9 years). Clinical features (age, size of tumor) and diagnostic tests (palpation, mammography, sonography and cytology) were found to be inaccurate in predicting benign (n = 22), borderline (n = 12) or malignant (n = 25) histological type. Limited surgery was associated with a relatively high proportion of local recurrence (enucleation/enucleoresection = 3/5, wide resection = 12/30) compared with mastectomy (2/24). No significant association was observed between the probability of local recurrence and patient's age, histological type or lesion size. Although the study confirms that limited surgery may cure phyllodes tumor, careful follow-up of all patients is needed, since no reliable risk factors for recurrence are available. In malignant cases, axillary node involvement was nil and distant metastases were infrequently observed (3/25). Axillary dissection and search for asymptomatic metastases is not recommended.     

乳腺叶状肿瘤17例诊治分析

[目的]总结乳腺叶状肿瘤的诊治情况。[方法]回顾分析17例经病理证实乳腺叶状肿瘤的临床资料。[结果]17例中良性11例,交界性3例,恶性3例。行乳腺肿瘤局部切除3例,乳腺肿瘤扩大切除7例,乳房切除术4例,乳房改良根治术3例,3例乳腺肿瘤术后出现复发。[结论]乳腺叶状肿瘤术前诊断较困难,主要依靠组织学检查,其局部复发与是否手术彻底切除密切相关。     

61例乳腺叶状肿瘤诊疗分析

目的探讨乳腺叶状肿瘤的临床诊断、病理以及治疗和预后的关系。方法回顾分析1973年4月至2005年2月收治的61例经病理证实为乳腺分叶状肿瘤患者的临床资料。结果61例患者平均年龄43岁,按WHO分类标准,其中36例为良性,19例为交界性,6例为恶性;34例行局部扩大切除术,18例行单纯乳房切除术,3例行单纯切除+植皮术,6例行改良根治术(1例发现淋巴结转移)。随访52例,平均随访92个月(16~378个月),共13例局部复发和转移,死亡4例。结论局部扩大切除或单纯乳房切除术是治疗乳腺分叶状肿瘤的首选治疗方法,但术前检查证实同侧腋窝淋巴结肿大的患者,考虑行改良根治术。复发治疗以手术为主,需足够的手术范围,以根治为目的。     

妊娠合并乳腺巨大恶性分叶状肿瘤2例报告及文献复习

目的:探讨乳腺恶性分叶状肿瘤的临床特点、治疗方法和预后。方法:回顾性分析2例妊娠合并乳腺巨大恶性分叶状肿瘤的诊治过程,并复习相关文献。结果:第1例患者经手术切除后局部复发,再次手术切除、局部放疗后随访至今,未见肿瘤复发转移;第2例患者,手术后短期内局部复发,再次手术后迅速出现双肺、胸膜转移,化疗疗效不显著,患者最终死亡。结论:乳腺恶性分叶状肿瘤的异质性显著,其诊治方法仍需要不断探索。     

The clinical features and prognosis of phyllodes tumors: a single institution experience in Taiwan

Background and objectives

The aim of this study was to document the clinical and pathological features of a single institutional series of Asian patients with phyllodes tumors, and to determine the prognosis, the adequate management and the predictive histological features.

Methods

The clinical data were retrospectively studied from the medical records and the pathological data from the Department of Pathology were utilized to identify 33 patients diagnosed with phyllodes tumors between 2003 and 2010.

Results

Eight patients had benign tumors, 13 borderline and 12 malignant. Nine patients (27 %) had recurrence. No patients classified as benign phyllodes tumors had recurrence, but those with malignant phyllodes tumors had a high recurrence rate (41 %). The 5-year disease-free survival was 59 %. The 5-year overall survival was 81 %. The width of surgical margin was not related to disease recurrence and stromal overgrowth was the only prognostic factor in terms of disease-free survival and overall survival.

Conclusions

The phyllodes tumors of borderline and malignant classification in Asian patients had a high recurrence rate. Clinical and pathological factors, except for stromal overgrowth, cannot predict disease recurrence. Further molecular research is warranted.     

乳腺叶状肿瘤预后因素的统计学分析

目的:探讨乳腺叶状肿瘤的预后因素。方法:对有随访结果的203例肿瘤的15个临床、病理学参数作统计学Log-Rank检验和Cox单及多因素分析。 结果和结论:术式、核分裂、瘤细胞异型性、肿瘤性坏死、瘤组织分化方向、瘤实质内薄壁血管数、单视野内核分裂增多、病理性核分裂、切除后复发、组织学等级和间质细胞密度11个参数为单风险因素,核分裂和肿瘤性坏死是独立的风险因素。     

Phyllodes tumor of the breast with a grossly malignant appearance: A case report

A huge phyllodes tumor of the breast that appeared grossly malignant in a 43-year-old woman is described. The patient suffered from a large breast tumor that suddenly increased in size over 5 months to occupy the entire breast. The tumor was hard, ulcerated and 20 cm in greatest diameter. Diagnostic imaging (US, CT and MRI) demonstrated a circumscribed mass with a large cystic cavity. She underwent total mastectomy under a diagnosis of malignant breast tumor. Grossly, the cut surface of the tumor showed a large cystic cavity surrounding a fleshy, hemorrhagic and necrotic mass with a lobulared or trabeculared appearance. Unexpectedly, benign phyllodes tumor (PT) without any stromal overgrowth was diagnosed histologically. She has been doing well since total mastectomy. In our case and in many other reported cases, PT does not show any distinctive correlation between pathologic findings and tumor behavior. Thus wide local excision is the preferred initial treatment for PT.     

Tumeurs phyllodes du sein à propos de 53 cas

PurposePhyllode tumors of the breast are fibroepithelial tumors similar to fibroadenomas but with a predominant conjunctive tissue component. These are composed of a connective tissue stroma and epithelial elements. They are rare with an incidence of 0.3–0.9% of all breast neoplasms. The present study demonstrates the recent experiences in diagnosis, therapeutical management and clinical follow-up of this disease.Patients and methodsThis is a retrospective study of the experience of the Institut National d’Oncologie (INO, Rabat) from 1998 to 2006.ResultsWe included 53 patients. Median age was 37.2 years (15–67), tumor size was 1–30 cm (median 10.25 cm). The histological diagnosis was based on the biopsy in (7.8%) cases and extemporany in 22% cases, distant metastasis occurred in two patients; the treatment consisted of a surgery. The median follow-up was three years. Local recurrence occurred in ten patients. Distant metastasis occurred in two patients and five patients have died.ConclusionThe confrontation of our results to the data of the international literature shows that the diagnosis of the phyllodes tumours is histological. The basis of the treatment is surgery. The adjuvant radiotherapy is very important in patients at high risk for local recurrence; chemotherapy has a badly defined place. The prognostic is based on the histological characters of the tissue conjunctive component of these tumours.     

乳腺叶状肿瘤研究进展

乳腺叶状肿瘤在乳腺肿瘤中较为罕见,其组织学上具有双向分化的特征,影像学有助于乳腺叶状肿瘤的诊断,组织病理学是诊断的金标准。该文通过对国内外乳腺叶状肿瘤的报道进行归纳、总结,从其临床特征、影像学表现、术前穿刺活检、标准手术方式的选择、术后是否行放化疗、内分泌治疗以及影响局部复发的因素进行总结,旨在提高该病的诊断率,避免过度治疗,为临床提供一定的参考意义。乳腺叶状肿瘤是否与相应基因有关,如何利用相关基因指导乳腺叶状肿瘤的治疗可能成为今后研究的重点之一。     

Phyllodes tumors of the breast

Opinion statement Phyllodes tumor is a rare fibroepithelial neoplasm of the breast with a very variable, but usually benign, course. Formerly known as cystosarcoma phyllodes, the designation “phyllodes tumor” with appropriate qualification regarding malignant potential based on pathologic features is now the agreed-upon term. The most important diagnostic distinction is from fibroadenoma—phyllodes tumors require complete excision with free margins even when pathologic features suggest benignity because of a proclivity to local recurrence. The most important component of therapy is wide surgical excision, and mastectomy is necessary only when free margins cannot be achieved without it. Involvement of axillary nodes is rare, and axillary dissection is not indicated. The role of radiation therapy and chemotherapy is not established and has not been studied in randomized trials due to the rarity of the tumor. At present, there is no consensus that patients with high-grade phyllodes tumors of the breast will benefit from either of these modalities.     

Scintimammographic findings of phyllodes tumor of the breast in a double-phase study with Tc-99m (V)DMSA and Tc-99m MIBI: a case report

We present a case of phyllodes tumor of the breast in a 78-year-old woman evaluated with Tc-99m (V)DMSA and Tc-99m MIBI scintimammography, acquired in separate sessions (10 and 60 min post-injection). Tc-99m (V)DMSA was accumulated intensely within the mass [tumor to background ratio (T/B) >3], whereas Tc-99m MIBI had significantly lower uptake (T/B 1.9). Histology revealed a phyllodes tumor (maximum diameter 15 cm) and approximately three mitoses over 10 fields of view (FOV) x40, foci of epithelial hyperplasia and apocrine metaplasia. Stromal Ki-67 expression was 7%. The tumor was considered to be benign and the patient underwent mastectomy. One year later the patient presented with local malignant recurrence of the disease with over 15 mitoses per 10 FOV. Tc-99m (V)DMSA seems to have an advantage over Tc-99m MIBI in detecting mesenchymal tumors with unforeseen biological behavior and Ki-67 over-expression, such as phyllodes tumors, even with primary negative histological findings.