Desmoid tumor associated with cystosarcoma phyllodes of the breast.

A case of desmoid tumor of 17 years' duration associated with cystosarcoma phyllodes of 17 months' duration is presented. Good initial response to radiation therapy of the desmoid tumor was shown. Poor response of cytosarcoma phyllodes to radiation therapy was noted. A comparison between the similarities and differences of the two tumors is presented.     

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.     

Radiotherapy to pulmonary metastases of a malignant phyllodes tumor of the breast

A bulky right breast tumor (15 × 15 cm) was discovered in a 54-year-old woman, and a simple mastectomy was performed, followed by 50 Gy of postoperative radiotherapy. Histologically, the tumor was malignant phyllodes tumor of the breast. Nine months after the mastectomy, multiple pulmonary metastases were detected and three lesions were treated with radiotherapy of 60 Gy/30 fractions for 43–54 days. Two lesions (16 × 12 mm and 18 × 16 mm) showed a partial response and no progression 2–4 months after the radiotherapy. The other lesion (22 × 18 mm) showed a partial response but progressed again 3 months later. She died of respiratory failure 18 months after the mastectomy. She also had muscle metastasis, but there were no locoregional recurrences. The malignant phyllodes tumor in this patient, showed a partial response to radiotherapy. Radiotherapy is considered useful for local control or symptomatic treatment of malignant phyllodes tumor.     

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。     

Frequent MED12 mutations in phyllodes tumours of the breast

Background:

Phyllodes tumours are rare fibroepithelial tumours of the breast, that include benign, borderline, and malignant lesions. Although the molecular basis of phyllodes tumours largely remains unknown, a recent exome study identified MED12 mutations as a sole recurrent genetic alteration in fibroadenoma, a common benign fibroepithelial tumour that shares some histological features with the phyllodes tumour.

Methods:

Forty-six phyllodes tumours and 58 fibroadenomas of the breast were analysed for MED12 mutations by using Sanger sequencing.

Results:

MED12 mutations were identified in 37 out of the 46 phyllodes tumours (80%). The prevalence of MED12 mutations was similar among benign (15/18, 83%), borderline (12/15, 80%), and malignant tumours (10/13, 77%). MED12 mutations were also identified in 36 of the 58 fibroadenomas (62%). The mutations were frequent among intracanalicular-type (24/32, 75%) and complex-type lesions (4/6, 67%), but were significantly less common among the pericanalicular-type lesions (8/20, 40%). A microdissection-based analysis showed that MED12 mutations were confined to the stromal components in both phyllodes tumours and fibroadenomas.

Conclusions:

MED12 mutations were frequent among the phyllodes tumours of the breast, regardless of the tumour grade. Phyllodes tumours and fibroadenomas share, at least in part, a common genetic background.     

Surgical treatment of phyllodes tumors of the breast: retrospective review of 172 cases

BACKGROUND AND OBJECTIVES: Phyllodes tumors (PTs) are uncommon biphasic breast tumors that usually occur in adult females. They are composed of a benign epithelial component and a cellular, spindle cell stroma forming a leaf-like structure. No one morphologic finding is reliable in predicting the clinical behavior of the tumor. The purpose of this study was to explore the clinicopathologic factors associated with outcome and metastasis. METHODS: We retrospectively reviewed the records of 172 patients seen at Mackay Memorial Hospital from January 1985 to December 2003. Clinical data analyzed included age, presenting symptoms and signs, tumor size, location, type of surgery, time to recurrence, and metastasis. The clinicopathologic factors associated with outcome and metastasis were analyzed statistically using the chi-square test with Yate correction. RESULTS: The mean follow-up was 71 months (range 7-237). The mean age was 37 years (range 11-73). The majority of tumors were found in the upper outer quadrant (46.0%), with an equal propensity to occur in either breast (48.8% vs. 50.0%). The pathologic diagnoses included 131 benign, 12 borderline, and 29 malignant lesions. Nineteen patients (11%) had a recurrence and three (1.7%) had metastases. The initial diagnosis of all 19 recurrent tumors were benign. Age, surgical approach, mitotic activity, and surgical margin were significantly correlated with recurrence (P = 0.029, 0.020, 0.048, and 0.00018, respectively). Stromal cellularity, stromal overgrowth, stromal atypia, mitotic activity, tumor margin, and heterologous stromal elements were significantly correlated with metastases (P = 0.032, 0.00008, 0.000002, 0.004, 0.005, and 0.046, respectively). Mammography and breast echo were not reliable for differentiating PTs from fibroadenomas (6.9% vs. 37.9% and 3.3% vs. 45%, respectively). Frozen section was of limited value (41.6%). The role of adjuvant radiotherapy and chemotherapy remains to be defined. Local excision, wide excision, or mastectomy with negative surgical margins yielded high local control rates (88.7%, 88.2%, and 100%, respectively), but local excision was associated with a relatively high percentage of positive surgical margins (18.3%). A total of 42 modified radical mastectomies were performed. The reasons for these procedures included a diagnosis of malignancy on frozen section or because the tumors were so large, they were assumed to be carcinomas. No axillary lymph node metastases were found. Fifteen patients in our series had tumors with infiltrating tumor margin, severe stromal overgrowth, atypia, and cellularity. All three patients with metastases (3/15) were in this group. Presence of metastases was significantly correlated with this group (P = 0.0000038). CONCLUSIONS: Wide excision with a clear margin may be the preferable initial therapy, even for malignant PTs. Routine axillary lymph node dissection is not recommended. Patients have tumors with infiltrating tumor margin, severe stromal overgrowth, atypia, and cellularity are at high risk for metastases.     

Osteogenic pulmonary metastases originating from a phyllodes tumour of the breast with osteosarcomatous differentiation

Malignant phyllodes tumour is an uncommon breast neoplasm which undergoes osteosarcomatous differentiation in 1.3% of cases. We document the plain film, CT and scintigraphic features of a case of pulmonary metastases from this rare primary tumour.     

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。     

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X线表现

目的探讨乳腺叶状肿瘤X线影像学特点,并与其病理对照,以提高对该病的诊断准确率。方法回顾性分析经手术病理证实有完整乳腺X线资料的乳腺叶状肿瘤50例共54个病灶,其中良性26个、交界性22个、恶性6个。结果 54个病灶中表现为伴或不伴钙化的肿块50个(92.6%),假阴性4个(7.4%)。50个肿块病变中良性23个、交界性21个、恶性6个。形状以分叶状、圆形或卵圆形最多见,分别占62.0%(31/50)、10.0%(5/50)、26.0%(13/50)。肿块边缘主要表现为清楚或部分清楚部分模糊,占80%(40/50),其余肿块呈浸润状及细小分叶状边缘,分别占18.0%(9/50)和2.0%(1/50)。肿块表现为高密度占74.0%(37/50),等密度占26.0%(13/50)。3个病灶肿块内含有钙化。边缘特征在良性与恶性肿瘤、交界性肿瘤与恶性肿瘤之间有明显差异,P_(良-恶)=0.003,P_(良-恶)=0.044。结论乳腺叶状肿瘤主要X线表现为分叶状或圆形、卵圆形的高密度肿块,钙化少见;边缘特征可在一定程度上提示良恶性叶状肿瘤的区别。     

Stromal neoplasms of the breast: a comparative flow cytometric study

We analyzed 42 mammary spindle cell neoplasms (10 conventional fibroadenomas, 8 giant fibroadenomas, 17 cystosarcoma phyllodes, and 7 stromal sarcomas) by flow cytometry to assess the diagnostic and prognostic relevance of DNA content analysis in the pathologic evaluation of these lesions. Our data indicate that all fibroadenomas were diploid, cystosarcoma phyllodes displayed diploid and aneuploid DNA content irrespective of their histological categorization, and that stromal sarcomas were all aneuploid and clinically aggressive. Diploid cystosarcoma phyllodes were biologically indolent, whereas most of the aneuploid neoplasms killed their hosts (P = 0.03). The present study indicates that a DNA content abnormality it is a reliable marker of malignancy in these neoplasms, and it may identify subsets of patients with variable biologic courses within the histopathologic spectrum of cystosarcoma phyllodes.     

Primary breast sarcoma: A review of 33 cases with immunohistochemistry and prognostic factors

The clinical and pathological features of 33 previously untreated patients with primary breast sarcoma were retrospectively analysed to evaluate the prognostic significance of histologic variables on survival. The series comprised 17 cystosarcomas phyllodes and 16 stromal sarcomas (excluding angiosarcomas).All tumors were reviewed and classified in similar fashion to extramammary soft tissue sarcomas. In addition, immunohistochemical studies were performed on paraffin sections with a panel of several antibodies directed against cytoskeletal filaments and cellular enzymes; five cases were also examined by electron microscopy.Most tumors were malignant fibrous histiocytoma (21 cases) and fibrosarcoma (6 cases) types. Surgery was the main therapy. Metastasis-free survival rate was significantly correlated only with histological grade, consisting of tumor differentiation, tumor necrosis, and mitotic activity. Courses and survivals of the cystosarcoma and stromal groups were identical, questioning the clinical value of this pathologic distinction. All local recurrence, metastasis, or death occurred within 30 months, though follow-up was much longer.Immunohistochemistry was disappointing for identification of specific histologic sub-types.     

乳腺叶状囊肉瘤的21例临床分析

目的 探讨乳腺叶状囊肉瘤的诊断和治疗方法。方法 对1987年9月至2004年12月收治的21例乳腺叶状囊肉瘤病人的临床资料进行回顾性分析。结果 21例中行局部切除术5例,局部扩大切除术9例,单纯乳房切除术4例,改良根治术2例,皮下腺体切除术加乳房再造术1例。随访至2004年12月,5年生存率95．2％,局部复发率9．5％。结论 乳腺叶状囊肉瘤是一种特殊类型的乳腺肿瘤,其预后与肿瘤的组织学分级、肿瘤大小以及手术切除是否彻底有关。     

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。     

Impact of primary local treatment on the development of distant metastases or death through locoregional recurrence in young breast cancer patients

In this study, we tested the hypothesis whether breast conserving therapy (BCT) compared with mastectomy is associated with a negative outcome in terms of distant metastases or death (DMD) and investigated the relation between locoregional recurrence (LRR) and DMD in young breast cancer (BC) patients. This study included a consecutive series of 536 patients ≤40 years of age at diagnosis with pathological T1N0-3M0 BC, treated between 1989 and 2005. A multistate survival model was used to evaluate the influences of local treatment and LRR on DMD, adjusted for potential prognostic factors. Patients were treated with mastectomy (N = 213) or BCT (N = 323). Median age at diagnosis was 36.3 years, with a median follow-up of 9.0 years. The 10-year actuarial cumulative incidence of DMD was 30.6 % after mastectomy and 26.3 % after BCT (P = 0.04). In total, 81 (15 %) LRRs were observed. After BCT, patients had a threefold higher risk of LRR than after mastectomy (HR 2.9; 95 % CI 1.6–5.3). Patients with LRR had a higher risk of DMD compared with patients without LRR (HR 5.5; 95 % CI 2.1–14.5). However, BCT was not negatively associated with DMD-after-LRR (HR 0.47; 95 % CI 0.2–1.1, BCT vs mastectomy). In conclusion, although LRR significantly affected DMD, the increased risk of LRR after BCT compared with mastectomy did not lead to a worse DMD outcome in BC patients ≤40 years of age.     

Analysis of failures following local treatment of isolated local-regional recurrence of breast cancer

Obe hundred fifty-seven patients with local-regional recurrence of breast cancer but without co-existing distant metastases were reviewed. The incidence of failure to control the local-regional recurrence was essentially the same whether the recurrence was treated with radiotherapy alone (62% ), surgery alone (76% ), or with a combination of the two (60 % ). A detailed analysis of the failures occurring in the patients treated with radiotherapy, with or without surgery, showed that most of the failures were because of a) inadequate doses of irradiation, b) the use of fields that were too small, and c) the lack of elective irradiation to the chest wall and supraclavicular fossa. Of the 100 patients with uncontrolled local-regional disease, 62% developed clinical symptoms that markedly impaired the quality of life. All of these symptoms were directly caused by the uncontrolled local-regional disease. Specific recommendations for the treatment of isolated local-regional recurrence are made.     

Outcome of treatment for ipsilateral breast tumor recurrence in early-stage breast cancer

Introduction: The aims of the study were to assess the outcome among patients with early breast cancer operated on with wide local excision who developed a subsequent ipsilateral breast tumor recurrence, and to identify risk factors for uncontrolled local disease. Uncontrolled local disease (ULD) was defined as the appearance of clinically manifest invasive adenocarcinoma in the remaining breast or on the ipsilateral chest wall which could not be eradicated with salvage treatment during the period of follow-up (2–18 years). Patients and methods: Eighty-five patients in a cohort of 759 patients, treated for invasive Stage I–II breast cancer with breast-conserving surgery 1976–1985 in Stockholm, with a subsequent ipsilateral breast tumor recurrence (IBTR) were reviewed retrospectively. The majority of the patients were premenopausal (58%), node negative (72%), and had received postoperative radiotherapy (79%). Median follow-up time following breast-conserving surgery was 13 (9–19) years. Multivariate Cox's hazard regression was used in the statistical analysis to identify prognostic factors for ULD. Results: The majority (n = 61) of the IBTR's were located in the original tumor quadrant and showed the same histopathological features as the primary tumor. Salvage mastectomy (n = 65) or reexcision (n = 14) were performed in 79 (93%) of the patients. Twenty-one patients developed ULD. Five years following the diagnosis of IBTR the disease-free survival was 59%, the cumulative incidence for ULD was 24%, and for death in breast cancer 34%. In the cohort of 759 patients, patients who received radiotherapy following the primary breast-conserving surgery had 1% cumulative incidence of ULD following the diagnosis of IBTR compared to 4% among patients that received no postoperative radiotherapy. The cumulative incidence at 5 years of ULD following salvage mastectomy was 12% compared to 33% after salvage reexcision. Patients operated on with breast-conserving surgery with an original tumor size < 15 mm, who were treated with salvage mastectomy for IBTR, had in multivariate analysis the lowest relative risk for ULD. Adjuvant chemotherapy following IBTR treatment did not seem to improve local tumor control. Following the diagnosis of IBTR, 78% (n = 21) of the patients with ULD and/or regional recurrence (n = 27), died of a disseminated breast cancer in contrast to 10% (n = 6) among the remaining 58 patients. Conclusion: Uncontrolled local disease is an important outcome measure following breast-conserving surgery. In this cohort, salvage mastectomy provided a superior local control rate compared to salvage reexcision. A higher although not statistically significant rate of ULD was also seen in patients who had not received postoperative radiotherapy as part of their primary treatment.This revised version was published online in October 2005 with corrections to the Cover Date.     

13例乳腺叶状肿瘤临床病理特征分析

目的：探讨乳腺叶状肿瘤的病理特征、诊断、鉴别诊断以及与治疗和预后的关系。方法：对经手术和病理诊断的13例乳腺叶状肿瘤的临床病理资料进行回顾性分析。结果：13例平均年龄为43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4例,交界性7例,恶性2例。结论：肿瘤的复发率随病理组织学等级递增而升高,随手术范围增大而下降,并与乳腺巨纤维瘤及其他乳腺肉瘤相鉴别。建议不管叶状肿瘤病理组织学分类如何,仍把它看作是低度恶性或恶性病变处理。     

Malignant phyllodes tumor of the breast: local control rates with surgery alone

PURPOSE: Patients with malignant phyllodes tumors of the breast (MPTB) are routinely treated with surgery alone. We performed a retrospective study to determine local control rates based on tumor size and type of surgery performed. METHODS AND MATERIALS: We reviewed records of 478 patients with MPTB treated between March 1964, and August 2005. The data were extracted from the IMPAC National Oncology Database consisting of merged tumor registries from 130 hospitals. RESULTS: Median follow-up was 64 months (range, 0-410 months). Actuarial 5-year local control rates were 79.4% for 169 lumpectomy patients and 91.2% for 207 mastectomy patients treated by surgery alone. Five-year local control rates for lumpectomy based on tumor size were 91% for 0-2 cm tumors, 85% for 2-5 cm tumors, and 59% for 5-10 cm tumors. For mastectomy patients, 5-year local control rates were 100% for 0-2 cm tumors, 95% for 2-5 cm tumors, 88% for 5-10 cm tumors, and 85% for 10-20 cm tumors. Multivariate analysis of overall survival found several factors to be significant including advancing age with each decade after 50 years of age, appearance of distant metastases, larger primary tumor size, and local control vs. local recurrence (Hazard Ratio [HR] 2.5, p < 0.05). CONCLUSIONS: Malignant phyllodes tumors of the breast local recurrence rates are 15% or greater for patients with tumors >2 cm treated by lumpectomy alone and tumors >10 cm treated by mastectomy alone. Adjuvant radiation therapy should be evaluated for these patients. This may be especially important because our study showed that local recurrence impacted on survival rates.