乳腺复发性叶状肿瘤临床病理分析

目的:探讨乳腺复发性叶状肿瘤临床及病理特征。方法:收集2011年01月至2019年12月在我院进行手术治疗的叶状肿瘤病例,并找出其中复发的病例,分析复发病例的临床及病理组织学特征。结果:叶状肿瘤137例,共有10例为复发病例,其中9例为单次复发,1例复发两次,复发病例中良性叶状肿瘤7例,交界性叶状肿瘤2例,恶性叶状肿瘤1例。所有的肿物均为局部复发,良性、交界及恶性叶状肿瘤复发率分别为5.9%、15.4%、20%。其中3例（30%）出现组织学升级,1例良性叶状肿瘤复发为交界性叶状肿瘤,1例交界性叶状肿瘤复发为恶性叶状肿瘤,1例良性叶状肿瘤第一次复发为交界性叶状肿瘤,第二次复发为恶性叶状肿瘤。免疫组化标记CD117、CD34、CD10、p53、p16在原发及复发肿瘤中表达无差异。Ki67增殖指数在复发病例中均升高,并且核分裂数也增多。结论:良性、交界性、恶性叶状肿瘤均可复发,其中恶性叶状肿瘤复发率最高,肿瘤多为局部复发,部分肿瘤复发后出现组织学升级,复发后肿瘤细胞增殖活性增强。     

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.     

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.     

Phyllodes tumors of the breast diagnostic and therapeutic dilemmas

BACKGROUND: This article compares experiences in the diagnosis and treatment of phyllodes tumors from 2 regional institutions with the relevant literature. PATIENTS AND METHODS: From 1991 to 2005, 2,848 breast cancer patients were treated in our institutions, 36 (1.44%) for phyllodes tumors. The average tumor size was 5.1 cm (range 1.4-19.6). Triple assessment was the standard diagnostic algorithm. Wide excision with tumor-free margins was carried out in 29 (80.5%) cases and mastectomy in 7 (19.4%) cases. Axillary lymphadenectomy was performed in patients with positive lymph nodes. RESULTS: Histology showed the phyllodes tumors to be benign in 27 (75.0%), malignant in 6 (16.6%), and borderline in 3 (8.3%) cases. Follow-up was from 5 months to 16 years. In this period, recurrences of 3 (8.3%) malignant and 2 (5.6%) benign phyllodes tumors were diagnosed and treated. 10 (27.7%) patients treated with wide local excision showed deformities in the form of scarring. The steroid receptor status was of no prognostic value in our patients, and chemotherapy was used in only 1 (2.7%) patient. 5-year survival was 86.2%. CONCLUSION: Our study shows that tumor size, margin infiltration, mitotic activity and degree of cellular atypia are important prognostic factors. Problems in diagnosing this condition arise from its similarity to fibroadenoma. Although wide local excision is usually the treatment of choice, tumor recurrence is common. Axillary lymphadenectomy in malignant phyllodes tumors is, in our opinion, still controversial.     

The extent of surgery and prognosis of patients with phyllodes tumor of the breast

In an attempt to clarify the controversial issues related to prognosis and therapeutic aspects of phyllodes tumors (PT), we retrospectively reviewed all cases of PT treated in our hospital during the last fifteen years. Re-examining the pathology material we found 84 cases, while thirteen more cases which had been initially classified as fibroadenomas with areas of phyllodes tumor were rejected from the analysis because they were classified as fibroadenomas. Based on the criteria proposed by Azzopardi and Salvadori and adopted by WHO, we found 55 benign PT (65.14%), 14 borderline PT (16.6%), and 15 malignant PT (17.8%). The median age of the patients with benign PT was 34 years, compared to 46.5 years for those with borderline tumors and 52 years for those with malignant. The median size of benign tumors was 3 cm, 9.5 cm for borderline, and 7.25 cm for malignant. Out of 55 patients with benign PTs, 37 underwent wide local excision and the remaining 18, with small tumors, underwent enucleation. In this group of patients, there was no recurrence after a median interval of 6.65 years. Eleven patients with borderline PT underwent wide local excision and three mastectomy; one immediately after an incomplete PT excision and the remaining two 8 months and 2 years later due to a locally recurrent PT (the last one proven histologically in the permanent biopsy of the recurrence to be malignant). Twelve patients with malignant PT underwent mastectomy, either during the same operation or following the results of the permanent section biopsy. Three more patients with malignant PT underwent wide local excision. The size of the tumor in these patients was relatively small and the pathology report indicated clear margins with normal breast tissue surrounding the tumor. One patient with 8 cm diameter malignant PT, who underwent mastectomy, passed away sixteen months later from widely spread metastases. Applying the criteria of Azzopardi and Salvadori, each case of PT can be managed successfully avoiding unnecessary mastectomies.     

Phyllodes tumor of the breast: an update

Phyllodes tumor is an uncommon biphasic breast tumor, with the ability to recur and metastasize, and it behaves biologically like a stromal neoplasm. Traditionally, phyllodes tumors are graded by the use of a set of histologic data into benign, borderline, and malignant. In most series, all phyllodes tumors may recur, but only the borderline and malignant phyllodes tumors metastasize. On the basis of histologic features, prediction of behavior is difficult. The expression of many biological markers, including p53, hormone receptors, proliferation markers, angiogenesis group of markers, c-kit, CD10 and epidermal growth factor receptor have been explored, and many have been shown to be variably expressed, depending on the grade of the tumor. These markers are, however, of limited value in predicting the behavior of the tumor. Recently investigators have reported a plethora of genetic changes in phyllodes tumors, the most consistent of which seems to be 1q gain by comparative genomic hybridization. Some candidate genes have been mapped to various sites, and preliminary data suggest that some of these changes may be related to recurrence. It is foreseeable that more exciting data will be generated to help us to understand the etiology and pathogenesis of phyllodes tumor.     

乳腺分叶状肿瘤八例报告

回顾分析8例乳腺分叶状肿瘤患者的临床病理资料，良性2例，交界性2例，恶性4例，患者年龄29～50岁，平均年龄41岁。肿块最大径平均6．6cm（3～38cm）。4例有肿块短时间内迅速增大的病史，4例曾接受2～3次肿瘤局部切除术，1例行局部扩大切除术，2例行乳腺单纯切除术，3例行乳腺改良根治术，1例胸壁复发的巨大肿瘤行皮肤与肋骨的全层切除、背阔肌-侧胸-腹直肌跨区皮瓣转移修复，1例在20个月内做过5次手术。随访3～72个月，8例患者均生存，其中2例分别于首次手术后8和21个月出现肺转移。回顾分析提示，乳腺分叶状肿瘤术前诊断困难，易局部复发，保证切缘阴性的局部扩大切除术是治疗乳腺分叶状肿瘤的合适的手段。     

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。     

Phyllodes tumors of the breast: natural history, diagnosis, and treatment

Phyllodes tumors of the breast are unusual fibroepithelial tumors that exhibit a wide range of clinical behavior. These tumors are categorized as benign, borderline, or malignant based on a combination of histologic features. The prognosis of phyllodes tumors is favorable, with local recurrence occurring in approximately 15% of patients overall and distant recurrence in approximately 5% to 10% overall. Wide excision with a greater than 1 cm margin is definitive primary therapy. Adjuvant systemic therapy is of no proven value. Patients with locally recurrent disease should undergo wide excision of the recurrence with or without subsequent radiotherapy.     

Comparison of Clinical Characteristics Between Benign Borderline and Malignant Phyllodes Tumors of the Breast

Background: Phyllodes tumors of the breast are rare fibroepithelial lesions, so relatively little is known aboutthis disease entity. The present study was designed to identify differences in clinical features between benignborderline and malignant phyllodes tumors. Materials and Methods: Data from 246 women with phyllodestumors of the breast treated in Cancer Hospital Chinese Academy of Medical Sciences between 2002 and 2012were collected and analyzed, including age at presentation, age at treatment, course, size of primary tumor,location, histological type, type of surgery and treatment, local recurrence, distant metastasis, fibroadenomahistory, disease-free survival and number of mitosis per 10hpf. There are 125 (55%) benign, 55 (24%) borderlineand 47 (21%) malignant tumors. Results: In univariate analysis, average age at presentation, average age attreatment, size of primary tumor, ulceration or not, type of primary surgery, distant metastasis and number ofmitosis per 10 hpf turned out to be statistically different among the three PT types (p=0.014, 0.018, <0.000, 0.003,<0.000, 0.001 and <0.000, respectively), while recurrence and disease-free survival (DFS) demonstrated trendsfor statistical significance (P =0.055 and 0.060, respectively). Multivariate analysis revealed distant metastasisand excision were significantly different in benign, borderline and malignant phyllodes tumors of the breast(p=0.041 and 0.018, OR=0.061 and 0.051). At the same time, size of primary tumor with p=0.052 tended to bedifferent between groups (OR=1.127). However, age at treatment, ulceration and DFS showed no statisticallysignificant variation (p=0.400, 0.286 and 0.413, respectively). Conclusions: Benign borderline and malignantphyllode tumors have different distant metastasis risk, different primary tumor size and different surgicalprocedures, and malignant PTs are more likely to be bigger and to metastasize.     

Analysis of phyllodes tumor recurrence according to the histologic grade

Local recurrence of phyllodes tumor (PT) of the breast is an adverse outcome that can result in sarcomatous degeneration. The aim of this study was to investigate the histologic and surgical factors associated with local recurrence. A total of 193 PT cases were studied: 145 (75.1 %) benign cases, 33 (17.1 %) borderline cases, and 15 (7.8 %) malignant cases. Stratifying our analysis according to histologic grade, we investigated the relationship between disease-free survival (DFS) and both histologic and surgical factors, including histologic grade, stromal cellularity, stromal atypia, stromal mitosis, stromal overgrowth, tumor margin, type of surgical procedure (local excision, wide excision, and mastectomy), surgical margin status, and radiation therapy. In the case of benign PT, all patients with local recurrences (3.4 %) had been treated with local excision, and all recurrent tumors were also benign. The local recurrence rate for locally excised benign PTs was not associated with surgical margin status or radiation therapy. In the case of borderline PT, local excision was associated with an increased local recurrence rate (P = 0.046). In malignant PT, small tumor size (≤4.0 cm) was associated with an increased local recurrence rate (P = 0.041). Univariate analyses indicated that surgical procedure (mastectomy < local excision < wide excision; P < 0.001) was significantly associated with shorter DFS in borderline PT. A positive surgical resection margin (P < 0.001) was associated with DFS in malignant PT. The factors associated with local recurrence differed with the histologic grade of PT, as did the features of local recurrence itself. In particular, benign PT had very low rate of local recurrence regardless of surgical margin status or radiation therapy, even when treated with local excision. In the case of benign PT, no recurrent tumors had worse histologic grades than the initial tumors.     

Surgical treatment of phyllodes tumors of the breast

Eighty-one female patients with phyllodes tumors of the breast, surgically treated from 1974 to 1983, were studied. Their age ranged from 9 to 88 years. According to histology, the series was divided into three groups, of 28 (34.5%) benign tumors, 32 (39.5%) border-line tumors, and 21 (25.9%) malignant tumors. Because ten patients were lost to follow-up, only 71 women could be evaluated. All the patients had received surgical treatment: 51 women had been treated conservatively (11 enucleations, 40 wide resections), and 20 had undergone radical operations (13 underwent total and five underwent subcutaneous mastectomies, whereas one underwent modified and one underwent radical mastectomy). The mean follow-up, for the three groups, was 106 months for benign, 84 months for borderline, and 82 months for malignant tumors; in no case was radical surgery followed by local recurrence: of 51 women conservatively treated, 14 experienced local relapse, i.e., one of 24 women with benign, ten of 22 with borderline, and three of 8 with malignant lesions. Only two of 47 patients (4.2%) with borderline or malignant tumors developed distant metastasis and died from disease. No relationship between tumor size and risk of local recurrence could be demonstrated, and no difference could be identified between borderline and malignant lesions, in terms both of local and distant relapse. Local recurrences do not appear to affect survival: as a consequence, wide resection should be the primary treatment. Enucleation is to be proscribed. Total mastectomy has been indicated for very large tumors and for local recurrences of borderline and malignant lesions. Axillary dissection is not worthwhile.     

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.     

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.     

Phyllodes tumor of the breast

PURPOSE: To better identify prognostic factors for local control and survival, as well as the role of different therapeutic options, for phyllodes tumors, a rare fibroepithelial neoplasm of the breast. METHODS AND MATERIALS: Data from 443 women treated between 1971 and 2003 were collected from the Rare Cancer Network. The median age was 40 years (range, 12-87 years). Tumors were benign in 284 cases (64%), borderline in 80 cases (18%), and malignant in 79 cases (18%). Surgery consisted of breast-conserving surgery (BCS) in 377 cases (85%) and total mastectomy (TM) in 66 cases (15%). Thirty-nine patients (9%) received adjuvant radiotherapy (RT). RESULTS: After a median follow-up of 106 months, local recurrence (LR) and distant metastases rates were 19% and 3.4%, respectively. In the malignant and borderline group (n = 159), RT significantly decreased LR (p = 0.02), and TM had better results than BCS (p = 0.0019). Multivariate analysis revealed benign histology, negative margins, and no residual disease (no RD) after initial treatment and RT delivery as independent favorable prognostic factors for local control; benign histology and low number of mitosis for disease-free survival; and pathologic tumor size < or = 3 cm and no tumor necrosis for overall survival. In the malignant and borderline subgroup multivariate analysis TM was the only favorable independent prognostic factor for disease-free survival. CONCLUSIONS: This study showed that phyllodes tumor patients with no RD after treatment have better local control. Benign tumors have a good prognosis after surgery alone. In borderline and malignant tumors, TM had better results than BCS. Thus, in these forms adjuvant RT should be considered according to histologic criteria.     

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。     

Small sized phyllodes tumor of the breast

From 1970 to 1988, 106 women (aged 13-63 years) suffering from phyllodes tumor of the breast underwent surgery at the Day Hospital in the Istituto Nazionale Tumori, Milan. Treatment consisted of enucleation in 57, enucleoresection in 42 and wide resection in seven. Ninety-two cases (86.8%) were benign, 12 (11.3%) borderline and two malignant. All the borderline and malignant tumors were submitted to wider resection as inpatients. The 12 borderline cases underwent wide resection while a subcutaneous mastectomy was performed in the two malignant cases. A mean follow-up of 49 months was carried out on 85 patients (range 1-186). The relapses, all in the benign group (6 cases; 6.52%), were much lower than reported by other authors (20-33%). This may be related to neoplasia size (less than 40 mm in 85.3%) and not to type of limited surgery. Although limited surgery was performed in 93.4% of cases (pre-operative diagnosis being unknown) the number of relapses was so low that re-operation with wider resection in healthy glandular tissue was not justified. However it is still performed in borderline and malignant phyllodes. The natural history of this tumor requires a prolonged follow-up since relapses may occur many months after operation (in our series 52).     

Jejunal intussusception due to malignant phyllodes tumor of the breast

Phyllodes tumors are rare fibroepithelial neoplasms of the breast; classified as benign, borderline, or malignant based on the mitotic activity, cellular atypia, and stromal overgrowth. Wide surgical excision is the treatment of choice. The most common locations for metastasis are lung, bone, and liver; small intestinal metastasis is extremely rare. Here we present the first patient with jejunal metastases and intussusception due to malignant phyllodes tumor of the breast. Adjuvant treatment of malignant phyllodes tumor needs to be investigated.     

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.