Primitive sarcoma of the breast: new insight on the proper surgical management

Background

Primitive sarcoma of the breast is a rare and challenging disease at high risk of recurrence and with poor prognosis. There are controversies in the diagnosis and management of such solid tumor due to its rarity and heterogeneity. This sarcoma is poorly responsive to both chemotherapy and radiotherapy, thus, surgery is the first and most important therapeutic approach. However, given the rarity of this type tumor it has not be possible to standardize unique guidelines for the proper surgical strategy to adopt. Here, we performed a retrospective study of new 10 cases of primitive sarcoma of the breast that underwent either mastectomy or a more conservative quadrantectomy, in the attempt to better standardize correct surgical indications.

Methods

Ten new cases of primitive sarcoma of the breast were registered between 2002 and 2012 and constituted the study group. They underwent either mastectomy or quadrantectomy and the clinical, prognostic and survival characteristics after surgery were analysed.

Results

Within the group of patients treated with mastectomy, two had metastasis and died because of that. Among the five patients treated with quadrantectomy four are alive and free of disease after 3 to 5 years follow-up, while the patient with sarcoma arising in pregnancy, although is still alive, developed lung metastases four years after surgery.

Conclusions

The first and most important therapeutic approach to primary sarcomas of the breast is surgical which has the purpose to achieve radical tumor excision to prevent local recurrence and skip metastases. However, given the rarity of the condition and the consequent small number of cases in this, like in similar studies, it is not possible to draw any definitive conclusions and further studies with larger numbers are necessary. However it would appear that performing a larger procedure such as mastectomy rather than performing a more limited one such as a quadrantectomy, has no advantage in terms of overall prognosis.     

Optimal management of sarcomas of the breast: an update

Breast sarcomas are rare mesenchymal-derived breast tumors. The small number of patients, the different histological subtypes, and the variation in clinical practice impairs the ability to draw firm practice recommendations. Patient management is often extrapolated from other soft tissue sarcomas, mostly of the extremities in which more clinical data is available. Surgical resection with negative margins is the goal of treatment, irrespective of the surgical procedure; the implication of radiation and chemotherapy is variable. Further advances in treatment should follow the assembly of breast sarcoma patients in specific cancer networks in specialized sarcoma referral centers. The characterization of molecular pathways active in tumorogenesis of these tumors may pave the way for the application of novel therapeutic agents.     

Radiothérapie des chloromes ou sarcomes granulocytiques : revue de la littérature

Granulocytic sarcoma, or chloroma, is a rare clinical entity, usually associated with a blood disease, including acute myeloid leukemia. Management strategies are based on the combination of systemic therapy and local therapy (surgery or radiation). Data for radiotherapy dose are derived from retrospective studies and case reports. We conducted a literature review using the Pubmed search engine to clarify the terms and indications for radiotherapy of chloromas.     

Alveolar soft part sarcoma metastatic to the breast

Metastasis to the breast is uncommon, with an incidence of 0.5–3%. Alveolar soft part sarcoma is rare, accounting for <1% of malignant soft tissue tumors, which are themselves unusual. Excluding contralateral breast and hematologic malignant disease, the primary lesion in most cases of metastasis to the breast is melanoma, small cell carcinoma of the lung, or ovarian carcinoma, although rhabdomyosarcoma is the most common primary tumor in children. We describe a 26-year-old woman with no history of malignant disease who presented with two masses in the right breast that clinical evaluations and ultrasonography indicated were fibroadenomas. Pathological studies after excisional biopsy, however, indicated alveolar soft part sarcoma. Subsequent computed tomography showed the primary tumor in the anterior left thigh and multiple bilateral lung metastases. Because of the presence of distant metastases, the patient was treated with chemotherapy. © 1996 Wiley-Liss, Inc.     

乳腺肉瘤6例临床治疗分析

目的　探讨乳腺肉瘤临床最佳治疗方案。方法　对我院 1995年 1月至 1999年 10月治疗的 6例乳腺肉瘤分析。结果　发病平均年龄为 5 2岁。 2例行细针穿刺涂片 ,其中 1例为阳性。 5例行快速冰冻切片确诊。 4例为乳腺纤维肉瘤 ,2例为乳腺恶性肿瘤纤维组织细胞瘤。 1例行乳腺单纯切除 ,5例行乳腺改良型根治术。总共切除腋下淋巴结 2 0个 ,均未发现转移。 6例病人的ER、PR均为阴性。结论　乳腺肉瘤首选手术治疗 ,以乳腺单纯切除为宜 ,没必要常规行腋窝淋巴结清扫。术后辅助放疗、化疗的效果不肯定。内分泌治疗意义不大。     

Diagnosis and management of primary breast sarcoma

Primary sarcoma of the breast is an extremely rare and heterogeneous disease. The rarity of this tumour limits most studies to small retrospective case reviews and case reports and has made clinicopathological study difficult. This article reviews the current literature on the diagnosis and management of breast sarcoma. The optimal treatment of breast sarcoma involves a multidisciplinary team prior to the initiation of treatment. Patients with tumours less than 5 cm that are easily resectable should undergo complete resection to the extent required to provide negative surgical margins. Negative surgical margins are more important for local recurrence and overall survival than the extent of surgical resection. Thus, neoadjuvant chemotherapy should be considered in order to shrink the tumour and help obtain negative surgical margins. Whether chemotherapy is indicated is primarily determined by tumour size. There is evidence that tumours larger than 5 cm are associated with an elevated risk of systemic failure and a poor prognosis. After surgical resection, patients with chemosensitive tumours should undergo additional adjuvant chemotherapy to treat micrometastatic disease. Radiation therapy should be used to improve local control in cases in which the tumour is larger than 5 cm and in cases with positive surgical margins. We propose to treat the patients according to the clinical practice guidelines in use for soft tissue sarcomas and address them to a reference centre for sarcoma. The appropriate treatment of breast sarcoma requires a multidisciplinary team approach necessitating experienced sarcoma surgeons, pathologists, radiotherapists and medical oncologists. Treating rare tumours in the same place should permit us to standardise pathological data and to include patients into multicentric radiotherapy or chemotherapy protocols to improve overall survival.     

Target therapy in gastrointestinal tract sarcoma: What is new?

Soft tissue sarcoma are rare tumors arising mostly from embryonic mesoderm, that can affect almost any part of the human body, including the gastrointestinal tract. The prognosis associated with soft tissue sarcoma is still poor, mainly because of the low efficacy of traditional approaches based on surgery and chemotherapy. As a result of genetic and molecular analysis, several new target therapies have been developed, leading to a significant improvement in the survival of patients affected by advanced disease. In this review we aim to explore the therapeutic potential and benefit of target therapy in the management of gastrointestinal soft tissue sarcoma and the possible complications or pitfalls of such an approach.     

孤立性颅内粒细胞肉瘤1例并文献复习

背景与目的：颅内孤立性粒细胞肉瘤较罕见，本文旨在探讨了解孤立性颅内粒细胞肉瘤的诊断、鉴别诊断及治疗原则。方法：回顾性分析1例孤立性颅内粒细胞肉瘤患者的临床资料．并复习相关文献进行讨论。结果：左额叶肿瘤术前误诊为脑膜瘤。行手术全切除，肿瘤累及硬脑膜及临近额眶骨，术后免疫组化确诊粒细胞肉瘤。外周血象及骨髓涂片正常。术后配合局部放射治疗。随访6个月无复发，外周血象无异常。结论：孤立性颅内粒细胞肉瘤临床罕见，易误诊为脑膜瘤或恶性淋巴瘤。确诊依靠病理学及免疫组化。手术切除为首选治疗方法。对局部浸润可配合放疗，而外周血象及骨髓涂片正常者不宜常规化疗，宜长期随访并监测血象，注意出现髓系白血病的可能。     

Tyrosine kinase inhibitors in sarcoma treatment

Sarcomas are a group of rare mesenchymal malignant tumors that arise from transformed cells of the mesenchymal connective tissue, which are challenging to treat. The majority of sarcomas are soft tissue sarcomas (STSs; 75%) and this heterogeneous group of tumors is further comprised of gastrointestinal stromal tumors (~15%) and bone sarcomas (10%). Although surgery remains the current primary therapeutic approach for localized disease, recurrent, metastatic and refractory sarcomas require cytotoxic chemotherapy, which usually yields poor results. Therefore the efficiency of sarcoma treatment imposes a difficult problem. Furthermore, even though progress has been made towards understanding the underlying molecular signaling pathways of sarcoma, there are limited treatment options. The aim of the present study was therefore to perform a systematic literature review of the available clinical evidence regarding the role of tyrosine kinase inhibitors (TKIs) in patients with recurrent or refractory STSs and bone sarcomas over the last two decades. Tyrosine kinases are principal elements of several intracellular molecular signaling pathways. Deregulation of these proteins has been implicated in driving oncogenesis via the crosstalk of pivotal cellular signaling pathways and cascades, including cell proliferation, migration, angiogenesis and apoptosis. Subsequently, small molecule TKIs that target these proteins provide a novel potential therapeutic approach for several types of tumor by offering significant clinical benefits. Among the eligible articles, there were 45 prospective clinical trials, primarily multicentric, single arm, phase II and non-randomized. Numerous studies have reported promising results regarding the use of TKIs, mainly resulting in disease control in patients with STSs. The lack of randomized clinical trials demonstrates the ambiguous efficiency of various studied treatment options, which therefore currently limits the approved drugs used in clinical practice. Research both in clinical and preclinical settings is needed to shed light on the underlying molecular drivers of sarcomagenesis and will identify novel therapeutic approaches for pretreated patients.     

双侧乳腺孤立性粒细胞肉瘤1例报告并文献复习

目的:讨论乳腺孤立性粒细胞肉瘤的临床及病理特征。方法:回顾性分析被确诊为双侧乳腺孤立性粒细胞肉瘤患者的临床资料、组织形态学、骨髓常规及免疫表型特征，并复习相关文献。结果:1例在发病前无白血病病史的62 岁女性患者体检发现双侧乳腺无痛性肿块。组织病理学可见肿瘤细胞呈列兵样排列或弥漫性分布，肿瘤细胞形态及大小一致，呈圆形或卵圆形，细胞质少，细胞核呈圆形或卵圆形，核分裂象及核仁易见，可见未成熟嗜酸性粒细胞散在分布。免疫组化提示MPO、CD45、CD34、CD68、CD117和CD43呈阳性，CD20、CD3、CD30、CD10和CKpan呈阴性。结论:双侧乳腺孤立性粒细胞肉瘤罕见。由于缺乏特异性临床特征，通常被误诊为淋巴瘤或其它良性肿瘤。肿瘤局部切除、系统化疗及放疗是其主要治疗手段。     

Neuroendocrine Carcinoma of the Breast: Current Evidence and Future Perspectives

Neuroendocrine carcinoma of the breast is considered a rare entity, and for this reason there are no data from prospective clinical trials on its optimal management. Early stage tumors are usually treated with the same strategy used for the other types of invasive breast cancer. Anthracycline- and taxane-based regimens represent the most frequently administered chemotherapy in neoadjuvant and adjuvant setting, as well as for metastatic disease, although combinations of platinum compounds and etoposide have been widely used, in particular for small-cell histology and tumors with a high proliferation index. For metastatic disease, a multimodality therapeutic strategy can be considered on an individual basis, with chemotherapy, endocrine therapy, peptide receptor radionuclide therapy, radiation therapy, surgery, or a combination of the above. In the near future, a better knowledge of the biology of these tumors will hopefully provide new therapeutic targets for personalized treatment. In this review, we discuss the current evidence and the future perspectives on diagnosis and treatment of neuroendocrine carcinoma of the breast.

Implications for Practice:

Neuroendocrine carcinoma of the breast (NECB) is a distinct entity of breast cancer. Clinical features and morphology are not helpful to distinguish NECB from other subtypes of breast cancer; therefore, immunohistochemistry markers for neuroendocrine differentiation, mainly chromogranin and synaptophysin, should be routinely used to confirm the diagnosis, especially in cases of mucinous or solid papillary carcinoma in which the suspicion of NECB may be relevant. Adjuvant treatment should be offered according to the same recommendations given for the other types of invasive breast cancer. An accurate diagnosis of NECB is also important in the metastatic setting, in which a multimodality approach including specific therapies such as peptide receptor radionuclide therapy can be considered.     

Characteristics and oncologic outcomes of patients with Ewing sarcoma of the scapula

Background and objectivesEwing sarcoma is the second most common bone sarcoma of childhood. Ewing sarcomas of the scapula are rare, with little known about their characteristics and outcomes. In this study, we describe the demographic characteristics, tumor characteristics, and oncologic outcomes of patients with Ewing sarcoma of the scapula.MethodsThis is a retrospective case series of thirty-four patients treated at three urban hospitals between 1993 and 2014 for Ewing sarcomas affecting the scapula. Their demographic data, tumor characteristics, and oncologic outcomes are reported and contrasted with data on Ewing sarcoma described in the literature.ResultsPatients in our case series were 59% male. The average age at diagnosis was 16 years. 44% of patients had metastatic disease at presentation. 26% of patients had a tumor size >8 cm in largest dimension at diagnosis. 9 patients in our series had the t (11; 22) translocation present. Patients had a survival rate of 68% at five years. No patients had local recurrence of disease. Compared with findings reported in the literature concerning Ewing sarcoma affecting other locations, patients with Ewing sarcoma of the scapula were slightly older at time of diagnosis, had a lower percentage of tumors with size > 8 cm in largest dimension at presentation, and more commonly had metastatic disease at presentation. Patients in our cohort had a 5-year survival rate of 68%, which is higher than the rate of approximately 55% as reported in the general literature.ConclusionsIn this study, we describe a retrospective case series of thirty-four patients with Ewing sarcomas of the scapula. This is the largest case series to date of Ewing sarcoma affecting this location to our knowledge. These results will contribute to the understanding of the clinical profile and oncologic behavior of Ewing sarcomas affecting the scapula.     

Multidisciplinarity and medical decision, impact for patients with cancer: sociological assessment of two tumour committees' organization

PurposeMedical practices in oncology are expected to be multidisciplinary, yet few articles studied how this may be concretely applied. In the present study, we evaluated the organization of two multidisciplinary committees, one for breast cancer and one for sarcoma, in a French Comprehensive Cancer Centre.MethodsBoth tumours were specifically chosen so as to emphasise substantial differences in relation with incidence, histological subtypes, management strategy, and scientific evidence. Between 2003 and 2004, 404 decision processes were observed, 210 for sarcoma (26 meetings) and 194 for breast cancer (10 meetings). The number of physicians who took part in the discussions and their medical specialties were systematically noted as well as the number of contradictory discussions, medical specialties represented in these contradictory discussions and the topics of contradiction. The last measured data was whether the final committee's decision was in conformity with the referent preferences or not. All these measures were related to the referent's medical speciality and working place, to the stage of the disease and to the disease management stage.ResultsCommittees’ specificities concerned their organization, referent's medical specialties, the number of participants in discussions and their medical specialties. Discussions in the sarcoma committee tended to be more multidisciplinary, involving more specialties. Initial strategy proposal for one patient was modified during the discussions for 86 patients out of 210 (41%) and for 62 out of 194 (32%) respectively for sarcoma and breast cancer. However, there was no significant difference in the rate of contradictory discussions between breast cancer and sarcoma committees (32% versus 41% respectively; P = 0.08). The rates of contradictory discussions were similar for localized cancers, local relapse and metastasis disease (37%, 41% and 34% respectively; P = 0.86).ConclusionsThe present study reports more than 30% of changes concerning strategy for patient with cancer due to multidisciplinary discussions. This indicates that, providing tumour committees are adapted to the pathologies’ characteristics, they can promote a collective and multidisciplinary approach to oncology.     

Myeloid sarcoma presenting as a colon polyp and harbinger of chronic myelogenous leukemia

Myeloid sarcoma, also known as granulocytic sarcoma or chloroma is an unusual accumulation of malignant myeloid precursor cells in an extramedullary site, which disrupts the normal architecture of the involved tissue. It is known to occur more commonly in patients with acute myelogenous leukemia and less commonly in those with myelodysplastic syndrome and myeloproliferative neoplasm, such as chronic myelogenous leukemia. The most common sites of involvement include bone, skin and lymph nodes. However, rare cases have been reported in the gastrointestinal tract, genitourinary tract, or breast. Most commonly, a neoplastic extramedullary proliferation of myeloid precursors in a patient would have systemic involvement of a myeloid neoplasm, including in the bone marrow and peripheral blood. Infrequently, extramedullary disease may be the only site of involvement. It may also occur as a localized antecedent to more generalized disease or as a site of recurrence. Herein, we present the first case in the English literature of a patient presenting with an isolated site of myeloid sarcoma arising in the form of a colonic polyp which, after subsequent bone marrow biopsy, was found to be a harbinger of chronic myelogenous leukemia.     

Development of secondary skull sarcoma after treatment for childhood acute myeloid leukemia

Secondary cancer is a serious late complication in childhood leukemia survivors. Here, we report a case of secondary skull sarcoma developing after treatment for childhood acute myeloid leukemia, including bone marrow transplantation (BMT). This patient had breast cancer 1 year before treatment for the skull sarcoma. The patient underwent macroscopic total removal of the skull tumor with bone margin with postoperative radiation therapy and did not develop tumor recurrence for 25 months. Our patient's experience suggests that survivors of childhood leukemia are at risk of developing skull sarcoma and that multi‐agent chemotherapy, including anthracycline, TBI used as conditioning for BMT, and development of GVHD, are possible risk factors. Considering the possibility of multiple secondary malignancies in such patients, careful long‐term follow up is mandatory.     

Single Fraction Radiation for Myeloid Sarcoma Is as Effective as Multi-Fraction Regimens for Tumor Regression and Control

Introduction/BackgroundMyeloid sarcoma is a rare extramedullary manifestation of immature myeloid/monocyte cells. Radiotherapy (RT) yields good local control, but data on different fractionation schemes are limited. The goal of this retrospective study was to share our institutional experience and assess volumetric regression with differential fractionation.Materials and MethodsWe evaluated patients treated for myeloid sarcoma between 2000 and 2019 and categorized them into Group A (treated with RT) and Group B (no RT). We assessed local control using cumulative incidence function analysis. Post-treatment imaging sequences were analyzed for volumetric calculations.ResultsForty-four patients with 80 lesions were assessed. Twenty-three patients with 52 lesions received RT (Group A), and 6 lesions received a single fraction of RT. There were 2 instances of local progression in Group A and 8 in Group B, with a cumulative incidence function estimate of local progression in Group A of 2.4% at 1 year and 6.9% at 2 years, significantly reduced compared to 29.7% and 35.5% in Group B, respectively (hazard ratio 0.13 [95% confidence interval 0.030.63], P = .011). No lesion treated with a single fraction of RT developed local progression. Volumetric analysis for 19 chronologically followed lesions (including 3 treated with a single fraction) revealed no difference in regression between single or multi-fraction treatment.ConclusionRT for myeloid sarcoma yields excellent local control and may be as effective in a single fraction as more protracted courses, though this requires validation. For a diagnosis associated with poor survival, a single palliative fraction may be optimal with potential for higher utilization.     

Primary breast sarcoma: clinicopathologic series from the Mayo Clinic and review of the literature

Primary sarcomas of the breast are extremely rare, with less than 0.1% of all malignant tumours of the breast. Mayo Clinic Surgical Pathology database was searched for all breast sarcoma from 1910 to 2000. Pathology reports and slides were reviewed and tumour types were determined. Metaplastic carcinomas and phyllodes tumours were excluded. There were 25 women ranging in age 24-81 years (mean 45 years). All but one patient presented with a palpable lump. Mastectomy was performed in 19 patients and lumpectomy in five patients. Histopathological diagnoses were fibrosarcoma (six), angiosarcoma (six), pleomorphic sarcoma (six), leiomyosarcoma (two), myxofibrosarcoma (three), hemangiopericytoma (one) and osteosarcoma (one). Tumour size ranged from 0.3 to 12 cm (mean 5.7). Low-grade lesions were observed in 10 cases and high-grade in 15. Overall, mean follow-up was 10.5 years. Local recurrence was observed in 11 patients and ranged from 2 to 36 months (mean 15 m), while distant metastasis was observed in 10 patients (40%) affecting lungs, bones, liver, spleen, and skin. Of the 25 patients, 12 have died of disease and six of other causes. Five-year overall (OS) and cause-specific survival (CSS) were 66 and 70%, respectively. OS and DFS at 5 years were 91% for tumours < or =5 cm and 50% for tumours >5 cm. Tumour size was significantly associated with OS (risk ratio=1.3 per 1 cm increase; 95% CI, 1.02-1.7; P=0.036). There was no significant difference in OS or CSS between low- and high-grade lesions. In this series, tumour size was a more valuable prognostic factor than tumour grade.     

Presentation of Axillary Metastases from Occult Breast Carcinoma

Axillary presentation from occult breast cancer is uncommon and continues to be a diagnostic and therapeutic challenge to physicians. Once the diagnosis of adenocarcinoma metastatic to an axillary lymph node has been confi rmed, a preoperative workup should be done. The current experience is based on several relatively small retrospective reviews and case reports. It is diffi cult to determine the best management of occult breast cancer. However, treatment of axillary lymph node dissection is recommended for local control and complete staging information. Treatment of breast should be a choice between breast conservation with whole-breast radiotherapy and mastectomy. Adjuvant systemic treatment should be offered.     

Understanding and management of male breast cancer: a critical review

Breast cancer is a rare disease in men representing nearly 1% of the total breast cancer cases worldwide. While treatments developed for women with breast cancer are often applied to treat men with breast cancer, however, lack of awareness of this disease leads to its detection at a later stage in men. This review discusses male breast cancer and draws comparisons with female breast cancer and discusses current treatments available to treat this disease. It is believed that this review shall provide concise and relevant information increasing the awareness of issues revolving around male breast cancer (MBC).     

Paget's disease of the male breast: a clinicopathologic study and a collective review

Two cases of Paget's disease of the male breast were detected in a retrospective histopathological review of 27 cases of male breast cancer treated during a period of 13 years from 1966 through 1978. The clinico-pathological data on these two rare cases have been compared with the 23 histologically documented cases of Paget's disease of the male breast from the literature.