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.     

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.     

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。     

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 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.     

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。     

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

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。     

Cystosarcoma phyllodes of the breast

Forty-nine patients with cystosarcoma phyllodes (CP), aged 13-81 years, (mean 35.2 years) were studied. Tumor size ranged from 1.9 to 14 cm (mean 5.2 cm). Mean follow-up period was 11.3 years. Tumors were histopathologically graded as benign, borderline or malignant. Forty-two tumors were diagnosed as benign; 4 borderline and 3 malignant. Six patients had recurrent disease within 6 years of their first surgery. Statistical analysis showed that age was not a significant factor for predicting recurrence or malignant histopathology. Five patients with relapse had borderline or malignant tumors larger than 4 cm. The histopathologic diagnosis was concordant with the clinical course. Multivariate analysis showed that tumor size and histology were significant and independent factors for disease-free interval. Breast-conserving surgery with a wide tumor-free margin is preferred in CP, and close follow-up is advised in cases with malignant or borderline histopathology and tumors larger than 4 cm.     

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.     

Resection and functional reconstruction of pelvic tumors

Objective To discuss the method of resection and reconstruction and effects in pelvic tumors. Methods 'Hie data of 27 cases with pelvic tumors treated with limb-salvage surgery during January 2005 to September 2015 were retrospective analyzed, including 15 males and 12 females, with age from 12 to 78 years old. Among these cases, there were 10 benign tumors, 1 borderline tumor, 14 malignant tumors and 2 metastatic tumors derived from other primary tumors. According to Knneking's division, it was consisted of 14 cases in region I , 2 cases in region II, 6 cases in region III, 2 cases in region 1 + II, 1 cases in region II + DI and 2 cases in region I +IV. Excision or curettage were chosen for benign tumors, and bone grafting or bone cement filling internal fixation were also used if necessary. For borderline and malignant tumors, radical resection was performed, meanwhile, reconstruction was done when pelvic ring continuity or acetabulum was destroyed, and palliative surgery was performed in some patients. All of them were followcd-up 4-125 months. Results There was no perioperative death. Among 10 benign patients, 1 case(10.0 °/c) of local recurrence was found. 8 (47.1 %) patients in 17 borderline and malignant patients were.dead, including 5 cases (29.4 %) dead of local recurrence, 2 cases (11.8 %) dead of uncontrolled lung metastasis and 1 case (5.9 %) dead of primary disease. According to Kaplan-Meier method, the 1-, 2-, 3-And 5-year survival rates of borderline and malignant patients were 75.6 %, 61.9 %, 43.3 % and 43.3 %, respectively. As for the functional recovery, the lower-limb fuel ion of patients treated by resection or reconstniction in region I , DI or IV got basically recovered, and the patients in region II needed one crutch to assist walking. Conclusion Selecting suitable resection or reconstruction methods according to the histology and the location of pelvic tumors can get favorable effects, furthermore, surgical methods need to individualize.     

A malignant phyllodes tumor of the breast in a 6-year old girl

We recently encountered a 6-year-old girl with a malignant phyllodes tumor of the breast. The patient's mother noticed a tumor on the right breast of her first doughter at 8 months after from her birth. The baby was brought to the Second Depertment of Surgery, University of Tokushima, at age 20 months. We recommended removal of the 3.5 x 2.9 cm tumor in the right breast, but it was not done. Next, she visited our department at 6 years of age because the tumor had gradually enlarged, reaching a size of 4.3 &timus; 4.0 cm. She underwent excisional resection of the tumor, and the tumor was diagnosed as a malignant phyllodes tumor of the breast coexisting with a borderline phyllodes tumor. To our knowledge, this is the youngest reported case of a malignant phyllodes tumor of the breast. Moreover, the malignant lesion was positive for estrogen receptor (ER) and showed strong proliferating cell nuclear antigen (PCNA) staining. On the other hand, the borderline part was negative for ER and showed weak PCNA staining. Thus, in the present case, the expression of ER, the exposure to estrogen (for example, the mother's estrogen during gestation) and increase in the proliferation rate may have played important roles in the mechanism of the transformation of the phyllodes tumor.     

Chromosomal aberrations and genetic relations in benign, borderline and malignant phyllodes tumors of the breast: a comparative genomic hybridization study

Phyllodes tumors are not quite rare fibroepithelial neoplasms of the breast that show a broad spectrum of clinical behaviour. The molecular genetic features of the heterogenous groups of neoplasms have not been studied in detail yet. We have used comparative genomic hybridization to analyze chromosomal copy number changes in 36 cases of phyllodes tumors (including benign, borderline and malignant phyllodes tumors, 12 cases each). The average number of chromosome copy changes (range) in benign, borderline and malignant phyllodes tumors were 5.58 (0–20), 14.08 (3–23), and 12.42 (0–29) respectively. In benign phyllodes tumors the number of gains and losses was in balance (2.50 vs 3.08), while in borderline and malignant phyllodes tumors gains occurred more often than losses (9.25 vs 4.83, 9.5 vs 2.92). The result suggests the molecular cytogenetics of borderline and malignant phyllodes tumors is similar, and the most striking difference with benign phyllodes tumors is an increased number of chromosomal gains in a nonrandom distribution. Gains of 4q12 seem especially to be involved in the progression of benign to borderline and malignant phyllodes tumors, possibly because of overexpression of oncogenes at these loci.     

Increased epidermal growth factor receptor (EGFR) expression in malignant mammary phyllodes tumors

Mammary phyllodes tumors are uncommon stromal-epithelial neoplasms, and are divided into benign, borderline malignant and frankly malignant groups on the basis of their histological features. Accumulating evidence shows that epidermal growth factor receptor (EGFR) is involved in the pathogenesis and progression of many malignancies. This study investigated 453 phyllodes tumors (296 benign, 98 borderline, 59 malignant) for EGFR expression using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) for gene amplification. The staining was correlated to tumor margin status, degree of malignancy, stromal cellularity, mitotic activity, nuclear pleomorphism and stromal overgrowth. Cases with strong positive IHC staining were selected for FISH. The overall positive rate for EGFR was 16.2% (48/296), 30.6% (30/98) and 56% (33/59) for benign, borderline malignant and frankly malignant phyllodes tumors, respectively. FISH demonstrated egfr gene amplification in 8% of immunohistochemically positive cases. The results of this study provide strong evidence that EGFR overexpression is involved in the pathogenesis of phyllodes tumors, although gene amplification may not be the major underlying mechanism for overexpression.     

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。     

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.     

Cystosarcoma phyllodes: Our institutional experience

Twenty‐six patients of Cystosarcoma phyllodes, treated between July 1994 and July 2001, were analysed retrospectively. Median age at presentation was 38 years (range 13?61 years). Mean size of the lesion was 6 cm. There were 77% left‐sided lesions and 23% right‐sided lesions. Histologically, 58% lesions were benign, 11% borderline and 31% malignant lesions. All patients underwent definitive surgical procedure in the form of wide local excision or mastectomy. Four patients received postoperative radiotherapy. Median follow‐up period was 35 months. Six patients showed recurrence, and four of these were malignant. Median disease‐free survival period was 34 months.