S-1 plus temozolomide as second-line treatment for neuroendocrine carcinoma of the breast:A case report

BACKGROUND Neuroendocrine carcinoma of the breast(NECB)is a rare type of malignant tumor.Due to the rarity of NECB,the relevant literature mostly comprises case reports.Available data on treatment options for NECB are very limited.CASE SUMMARY A 62-year-old woman presented to our hospital in October 2016 for intermittent vomiting and diarrhea and masses in the liver found on abdominal computed tomography(CT)imaging.She was diagnosed in July 2012 with neuroendocrine carcinoma of the right breast in local hospital.The patient initially presented with a painful lesion of the right breast.She then undergone surgical resection and adjuvant chemotherapy with pirarubicin and paclitaxel for four cycles as well as endocrine therapy.She was regularly followed every 3 mo after surgery.Enhanced abdominal CT imaging at our hospital revealed multiple suspicious masses in the liver with the largest lesion measuring 8.4 cm×6.3 cm.Chest CT revealed masses in the anterior chest wall and lung.Core needle biopsy of the lesion revealed liver metastases of NECB.A bone scan showed right second anterior rib metastases.Upper endoscopy and colonoscopy did not provide any evidence of another possible primary tumor.She stopped receiving endocrine therapy and then received etoposide and cisplatin(EP)chemotherapy as a firstline treatment regimen for six cycles at our hospital after liver,bone,and lung metastases.On October 2017,the chemotherapy regimen was changed to S-1(40mg twice daily,days 1-14)combined with temozolomide(200 mg once daily,days 10-14)(STEM)every 21 d as a second-line treatment regimen due to disease progression.Progression-free survival(PFS)and adverse effects after treatment were analyzed,and the efficacy of the STEM regimen was assessed using RECIST version 1.1.This patient achieved a partial response after using the STEM regimen,with a PFS of 23 mo.Adverse effects included only grade 1 digestive tract reactions with no need for a reduction in chemotherapy.CONCLUSION This case report suggests that the STEM regimen may be effective and well tolerated as the second-line treatment for advanced NECB.STEM is still highly effective in patients who show disease progression with the EP regimen.More evidence is needed to prove the validity of STEM.

Clinicopathological Study of Neuroendocrine Carcinoma of the Breast

Introduction: Neuroendocrine carcinoma (NEC) occurs mostly in the digestive organs, such as the pancreas and gastrointestinal tract, and the lungs. Primary NEC of the breast is a rare entity. There are not many studies on this disease, and this study was carried out in order to know the clinical pathology of this disease. Methods: Of 2354 patients who underwent surgery for breast cancer in our hospital during the period from January 2000 to July 2015, 8 (0.34%) were pathologically diagnosed with NEC of the breast. This study is retrospectively registered. Result: The histological types were small cell carcinoma in one patient and invasive ductal carcinoma (IDC) with neuroendocrine differentiation in the remaining 7. The mean patient age was slightly higher than that of patients with usual IDC. On pathological examination, the NEC tumors were more hormone dependent and often HER2 negative, as compared to usual IDC, though there was no significant difference in nuclear grade. The patients with NEC of the breast showed positivity for neuroendocrine markers on immunohistological staining, and had favorable outcomes. Conclusion: NEC of the breast is rare, and there is no established consensus regarding the pathological significance, prognosis, and treatment method. Further accumulation of cases is necessary.

Solid neuroendocrine breast carcinoma:mammographic and sonographic features in thirteen cases

This study aimed to determine and quantitate the mammographic and sonographic characteristics in 13 cases of solid neuroendocrine breast carcinoma(NEBC) and to analyze the association of radiological findings with the clinical and histopathologic findings.The clinical data and imaging findings of 13 female patients with histologically confirmed solid NEBC were reviewed.Imaging data were evaluated by two radiologists for a consensual diagnosis.All patients presented with one palpable mass;only 1 experienced occasional breast pain,and 5 complained of fluid discharge.In 7 patients,the masses were firm and mobile.Regional lymph node metastasis was noted in only 1 patient.For the 10 patients who underwent mammography,6 had a mass,1 had clustered small nodules with clustered punctuate microcalcifications,2 had asymmetric focal density,and 1 had solitary punctuate calcification.Most of the masses had irregular shape with indistinct or microlobulated margins.For the 9 patients who underwent ultrasonography(US),9 masses were depicted,all of which were hypoechoic,mostly with irregular shape and without acoustic phenomena.Different types of acoustic phenomena were also identified.One patient had developed distant metastases during follow-up.NEBC has a variety of presentations,but it is mostly observed on mammograms as a dense,irregular mass with indistinct or microlobulated margins.Sonographically,it typically presents as an irregular,heterogeneously hypoechoic mass with normal sound transmission.Histories of nipple discharge and calcification observed using imaging are not rare.

A case report of primary small cell carcinoma of the breast and review of the literature

Primary small cell carcinoma (SCC) of the breast, an exceedingly rare and aggressive tumor, is often characterized by rapid progression and poor prognosis. We report a case of primary SCC of the breast that was diagnosed through pathologic and immunohistochemical examinations. Computed tomography (CT) scans failed to reveal a non-mammary primary site. Due to the scant number of relevant case summaries, this type of tumor is proved to be a diagnostic and therapeutic challenge. Therefore, we also reviewed relevant literature to share expertise in diagnosis, clinicopathologic characteristics, treatment, and prognosis of this type of tumor. Future studies with more cases are required to define more appropriate treatment indications for this disease.

Papillary carcinoma of breast: Minireview

The term "intracystic papillary ductal carcinoma in situ " constitutes only 0.5% to 1% of all breast cancers.It is usually seen in postmenopausal age group.Herein,we are presenting a minireview about this unusual breast malignancy usually difficult to diagnose on clinical grounds and highlighting modalities of diagnosis and management.

Studies on the DNA content of breast carcinoma cells with neuroendocrine differentiation

OBJECTIVE: To make quantitative analysis of DNA content of breast cancer with neuroendocrine (NE) cells and its significance. METHODS: Using MIPS-III image analyzer, DNA content and 9 parameter measurements of the tumor nuclei were made in both NE positive (17) and negative (64) breast carcinomas. RESULTS: Out of 81 breast carcinomas, 17 cases were NE positive while 64 cases were NE negative. In the NE (+) cases, the integral optic density, mean optic density, DNA index, DNA stemlines peak, > 5c aneuploidy cells and the rate of aneuploidy cells were all lower than those in the NE negative breast carcinoma cases (P

A case of primary neuroendocrine breast carcinoma that responded to neo-adjuvant chemotherapy

Primary neuroendocrine breast carcinoma （NEBC） is a very rare type of breast cancer. Two characteristic biomarkers, namely, CgA and Syn, should be immunohistochemically detected to diagnose NEBC. In this study, a 43-year-old woman with a large mass of 8.3 cm × 2.9 cm in her right breast was reported. The patient was pathologically diagnosed with NEBC after specific markers, including CgA and Syn, as well as few differential markers, such as CK7, ER, PR, C-erbB-2, NSE, and E-cadherin, were immunohistochemically detected. The patient showed a remarkable response to four cycles of neo-adjuvant chemotherapy （partial response based on RECIST criteria） and sequentially underwent modified radical mastectomy. Moreover, the diagnosis and treatment of NEBC based on this case and available related literature were discussed.

乳腺实性乳头状癌临床及病理特征分析

目的探讨乳腺实性乳头状癌(SPC)临床与病理特点、治疗方法。方法回顾性分析2014年1月至2023年12月确诊的28例乳腺SPC患者(原位型9例、浸润型19例)的临床特征、病理形态及免疫组化染色特征。结果28例SPC患者发病年龄29~82岁(中位年龄79岁),临床表现为乳腺肿块和/或乳头溢液。均手术切除,组织学病理:原位型SPC 9例,浸润型SPC 19例。根据肿瘤细胞巢的边缘完整程度分为原位型和浸润型。瘤细胞形态均匀,呈卵圆形或梭形,细胞核为低-中级别。免疫表型,两种类型的肿瘤细胞ER、PR均呈弥漫性强阳(>90%),大多数HER-2表达阴性(92.8%),CgA阳性率35.7%,Syn阳性率96.4%,CD56阳性率平均28.6%,Ki67为1%~40%。结论乳腺SPC好发于老年女性,两种类型SPC的病理特征、免疫表型均具有较大差异。

RB1及INSM1在乳腺实性乳头状癌中的表达及意义

目的研究RB1及INSM1在乳腺实性乳头状癌(SPC)中的表达及意义。方法对濮阳市油田总医院2013—2022年的17例乳腺实性乳头状癌进行病理分析,并用免疫组化方法对其进行Syn、CgA、CD56、INSM1、RB1标记。结果17例病例均行免疫组化:11例表达Syn,6例出现CD56表达,3例出现CgA表达,10例表达INSM1,17例患者均表达RB1。其中INSM1与Syn、CD56的表达阳性率差异无统计学意义(P>0.05),但高于CgA的阳性率(P<0.05)。结论INSM1在乳腺实性乳头状癌中存在较高的阳性率,可用于SPC的诊断;RB1在乳腺实性乳头状癌中表达未缺失,对于SPC的诊断与鉴别诊断有提示意义。

乳腺腺样囊性癌的临床病理特征与MYB检测

目的 探讨乳腺腺样囊性癌(adenoid cystic carcinoma, AdCC)的临床病理学特征、治疗与预后。方法 回顾性分析14例乳腺AdCC患者的临床病理资料,行HE、免疫组化和FISH检测,并随访。结果 14例AdCC患者均为女性,年龄43~70岁,包括10例经典型和4例实性-基底细胞样腺样囊性癌(solid-basaloid adenoid cystic carcinoma, SB-AdCC)。肿瘤由上皮、肌上皮和基底样细胞组成,呈筛状、管状以及实性巢状排列,间质呈纤维黏液样或玻璃样变。SB-AdCC的瘤细胞中-重度异型,核分裂象及坏死易见,常合并导管原位癌。免疫表型:ER(1/14)、PR(1/14)、HER2(0/14)、CK7(14/14)、p63(12/14)、CK5/6(14/14)、CD117(13/14)、MYB(9/14),经典型AdCC与SB-AdCC的Ki67平均增殖指数分别为13.2%与46.1%。FISH检测:MYB重排率在经典型AdCC与SB-AdCC分别为55.6%(5/9)与25%(1/4)。14例患者接受了不同范围的手术切除,并组合放疗和(或)化疗。随访期内(2~62个月)1例SB-AdCC患者因肺和肝转移而死亡,10例随访患者均无瘤生存。结论 SB-AdCC较经典型AdCC的侵袭性更强,MYB基因重排频率低,免疫组化检测MYB蛋白对辅助诊断SB-AdCC具有潜在价值。

乳腺MRI对实性乳头状癌的诊断价值

目的:分析乳腺实性乳头状癌(solid papillary carcinoma,SPC)的磁共振成像(magnetic resonance imaging,MRI)特征,探究MRI对于SPC的诊断价值。方法:回顾并收集2017年1月—2021年12月上海交通大学医学院附属新华医院经手术后病理学检查证实为SPC且行术前MRI检查的患者57例(共61个SPC病灶)。57例患者中,行术前乳腺X线摄影及超声检查者分别为45例(48个SPC)和52例(55个SPC)。根据术前乳腺影像报告和数据系统(Breast Imaging Reporting and Data System,BI-RADS)分类结果,以BI-RADS≥4A类为可疑恶性,计算乳腺X线摄影、超声及MRI对SPC的检出率及诊断准确度。病灶形态分为非肿块强化(non-mass enhancement,NME)与肿块两组,两组大小比较采用Mann-Whitney U检验,伴随导管扩张的差异采用χ^(2)检验。结果:乳腺X线摄影、超声及MRI对SPC的检出率为分别为64.6%(31/48)、83.6%(46/55)和100.0%(61/61),诊断准确度分别为52.1%(25/48)、65.5%(36/55)和98.4%(60/61)。在MRI上,SPC表现为NME较肿块更多见(67.2%vs32.8%)。NME较肿块病灶更大[2.5(1.6,4.0)cmvs1.4(1.0,1.8)cm,P<0.001],伴随导管扩张的阳性率更高[82.9%(34/41)vs 25.0%(5/20),P<0.001]。结论:乳腺MRI对于SPC的检出率及诊断准确度均高于乳腺X线摄影和超声检查。在MRI上,SPC表现为NME较肿块更多见,前者病灶更大,更常伴随导管扩张。

乳腺实性乳头状癌的超声表现及其病理学相关性研究

目的:探讨乳腺实性乳头状癌(solid papillary carcinoma of the breast,SPC)的灰阶超声、彩色多普勒超声及超声弹性成像表现,并探讨SPC的超声表现与其病理学检查结果的相关性。方法:分析71例经术后病理学检查证实的SPC患者的临床资料,共包括75个SPC病灶的灰阶超声、彩色多普勒超声表现和35个SPC病灶的超声弹性成像表现。比较不同病理学亚型SPC的超声表现及与病理学检查结果的相关性。结果:SPC的超声表现大多为单发的低回声实性肿块,呈水平生长,形态不规则,边缘不光整,后方回声增强或不变,可伴有导管扩张及钙化,Adler血流分级Ⅱ~Ⅲ级,阻力指数(resistance index,RI)为0.62~0.84。几乎不伴有腋窝淋巴结转移。75个SPC病灶病理学分子分型均为Luminal A型。Ki-67增殖指数在42个原位SPC病灶中均<20%,在15个浸润性SPC中为20%~60%,两者差异有统计学意义(P=0.000)。结论:SPC超声表现具有一定特征性,结合灰阶、彩色多普勒超声及超声弹性成像可提高其诊断准确度,但超声无法鉴别原位SPC及浸润性SPC,Ki-67增殖指数与SPC是否浸润有关。

Metastatic Breast Neuroendocrine Cancer in Pregnancy:A Case of an Oncologic Emergency and a Review of Literature

Breast neuroendocrine carcinoma is a rare entity.It constitutes less than 0.5%of breast malignancies,and is usually diagnosed in older women.The occurrence of this type in young patients during pregnancy is extremely rare.Only 2 cases were previously reported.Both were diagnosed at earlier stage with the appearance of a palpable breast mass.Hereby,we present the case of a young patient at 28 weeks’gestation admitted for severe diffuse back pain and neurologic deficit due to spinal cord compression at the level of C5 vertebra,and nerve root compression at the level of L5 vertebrae.To the best of our knowledge,this is the first case of oncologic emergency during pregnancy due to a metastatic poorly differentiated breast carcinoma with neuroendocrine differentiation in the absence of a detectable primary focus of malignancy in the breast.We also discuss the management and the obstetrical outcome of this patient.

乳腺神经内分泌癌35例临床病理分析

目的介绍并讨论乳腺神经内分泌癌的临床病理学特征。方法对35例乳腺神经内分泌癌的临床表现、组织学形态、免疫表型及预后进行研究。结果35例均为女性患者,发病年龄28～95岁（平均60.4岁）。肿块大小0.8～5cm（平均2.04cm）。组织学形态包括：实性黏附型（15例）、腺泡型（10例）、实性乳头型（5例）、细胞黏液型（2例）、小细胞/雀麦细胞癌（2例）、大细胞癌（1例）。所有病例NSE和CK阳性表达,分别有34例（97.1%）和21例（60.0%）表达Synaptophysin和chromogranin A,腋下淋巴结转移率为25.0%（5/20例）,除1例因发生肺和骨转移死亡外,其余患者均健在,随访时间2～76个月（平均32.1个月）。结论乳腺神经内分泌癌是一少见的独立病种,病理形态复杂,其生物学行为特性还需大样本较长期的随访观察。

乳腺神经内分泌癌的临床病理学特点

目的 探讨具有神经内分泌特征乳腺癌的临床病理特点 ,加深对其认识。方法 观察 5例乳腺神经内分泌癌的组织学特征并进行免疫组化染色 ,判定标准为≥ 5 0 %肿瘤细胞表达Syn、CgA或NSE。 结果 4例女性 ,1例男性。年龄 5 4～ 90岁(平均 70岁 )。肿瘤直径 2 5～ 5 5cm(平均 3 5cm)。有淋巴结转移者 2例。组织学形态包括富于细胞的黏液型、实性岛状型、弥漫实性粘附型、非典型类癌型和小细胞癌型。 5例均表达Syn、CgA、NSE、AE1/AE3和EMA ;2例表达Lue 7,2例表达CK7;3例表达E cad ;S 10 0蛋白均阴性 ,2例ER和PR阳性 ,3例 p5 3阳性 ,1例表达c erbB 2 ,4例表达bcl 2 ,Ki 6 7阳性率17%～ 85 %。随访时间 4～ 6 9个月 (平均 32 2个月 ) ,除小细胞癌患者死亡外 ,均存活。结论 乳腺神经内分泌癌易发生在老年人 ,除小细胞癌外其他类型预后较好 ,它们在形态、功能和表型上常呈多向性 ,应该将它们从普通型的乳腺癌中区分出来。

乳腺实性乳头状癌73例临床病理诊断

目的对乳腺实性乳头状癌(solid papillary carcinoma,SPC)的临床病理特征和免疫表型特点、预后和鉴别诊断进行探讨。方法收集伴或不伴有浸润癌的SPC共73例,总结其临床资料、大体和组织病理特征,并行透射电镜观察及免疫组织化学EnVision法染色。选用抗体包括CK、肌上皮标记、神经内分泌标记、增殖标记Ki-67和ER、PR、c-erbB-2等。结果本病好发于老年女性,发病平均年龄64.7岁。肿瘤最常见的临床症状为乳腺肿块和乳头溢液。行腋窝淋巴结清扫术43例中有31例检出癌转移。镜检所有标本均见到实性乳头状病变,25例伴有黏液分泌。周边常可伴有导管内乳头状瘤。肿瘤细胞呈多边形、卵圆形或梭形,呈印戒样。胞质丰富,呈嗜酸性或细颗粒状。细胞核轻度或中度异型,51例核分裂象5个/10HPF。43例伴发浸润癌。肿瘤基底型CK表达呈阴性。平滑肌肌动蛋白SMA、p63在乳头轴心肌上皮的阳性率分别为91.8%、67.1%,在导管周围肌上皮的阳性率分别为91.8%,73.9%。CgA和Syn以及NSE阳性率分别为89.0%,86.3%,95.9%。Ki-67平均阳性指数为10.2%。73例行ER、PR染色的肿瘤大部分呈阳性,Her-2大部分呈阴性。电镜下可见到细胞内的神经内分泌颗粒。结论乳腺SPC是一种低度恶性的乳腺导管内癌,好发于老年女性,有其独特的组织形态、免疫组织化学特征,部分SPC与乳腺黏液癌和神经内分泌癌相关。随访资料显示SPC具有良好的预后。

乳腺实性乳头状癌11例临床病理分析

目的探讨乳腺实性乳头状癌的临床病理学特点、免疫表型。方法对11例乳腺实性乳头状癌的临床病理学特点、免疫表型及淋巴结转移情况进行分析。结果 11例实性乳头状癌均为女性,8例为原位癌,3例伴浸润癌成分,平均年龄63.2岁。11例实性乳头状癌均表现为乳腺肿块,其中3例为乳头溢血。所有病例大体界限清楚,肿瘤细胞围绕纤细的纤维血管轴心呈实性结节状增生,肿瘤细胞形态单一,核染色质细腻,核分裂象<5个/10 HPF,8例可见细胞内外黏液。免疫表型:ER、PR均弥漫强阳性,CK5/6和HER-2均阴性,5例在瘤巢周围可见稀少的p63阳性细胞,4例瘤巢周围可见CK5/6和CD10阳性细胞,3例伴浸润癌成分者,瘤巢周围无p63、CK5/6、CD10阳性细胞;5例表达神经内分泌免疫标记Syn,6例表达Cg A。9例行腋窝淋巴结清扫术,其中1例发生淋巴结转移。结论乳腺实性乳头状癌是一种少见的好发于老年女性的乳腺癌,以肿瘤细胞排列呈实性乳头状结节为特征,常有细胞内外黏液分泌,为腺腔A型乳腺癌的免疫表型,并表达神经内分泌免疫标记,预后良好,较少发生腋窝淋巴结转移。

乳腺神经内分泌癌18例病理形态观察

目的：分析乳腺神经内分泌癌的病理形态特征，阐明其诊断要点。方法：对确诊为乳腺神经内分泌癌的切除标本１８例进行光镜观察和神经元特异性烯醇化酶（ＮＳＥ）及嗜铬素Ａ（ＣｇＡ）免疫组织化学染色、８例进行电镜观察，并复习其临床资料。结果：本组患者均为女性，年龄３６～７７岁，平均５３岁，肿瘤大小１２～５５ｃｍ，平均２７ｃｍ。１８例乳腺神经内分泌癌中，典型类癌５例，不典型类癌８例，未分化型小细胞癌５例；电镜下８例癌细胞胞浆内均找到神经内分泌颗粒（ＮＥＧ）；５０％以上癌细胞免疫组织化学染色显示ＮＳＥ及ＣｇＡ均为阳性反应。结论：乳腺的神经内分泌癌作为乳腺癌的一种罕见类型，我们认为应按照其分化程度及组织结构分为类癌、不典型类癌及未分化型小细胞癌。

乳腺实性乳头状癌临床病理特征及预后分析

目的探讨乳腺实性乳头状癌(SPC)的临床病理特征。方法回顾性分析23例SPC的临床表现、病理形态学和免疫组化的特征及预后随访。结果 23例SPC患者首发症状乳头溢液16例,乳腺肿块7例。超声检查BI-RADS 4级以上占60%(6/10)。钼靶检查BI-RADS 4级以上占61.53%(8/13)。8例SPC伴浸润中Luminal A型5例,Luminal B型3例。原位SPC组和SPC伴浸润组比较,在平均年龄、平均直径、神经内分泌标志物、Ki67及淋巴结转移上差异无统计学意义(P>0.05),而在肌上皮标志物P63和CK5/6上差异有统计学意义(P=0.001、P=0.019)。21例患者随访均未见复发。结论 SPC是一种预后良好且少见的独立亚型的乳腺癌。影像学及乳管镜易漏诊,病理易误诊,临床病理医生应重视更好的精准治疗。

乳腺神经内分泌癌的超声表现及其临床、病理特征

目的观察乳腺神经内分泌癌的超声表现及其临床、病理特征。方法回顾性分析经病理证实的5例乳腺神经内分泌癌的临床、超声表现和组织病理学特征。结果患者均为女性,年龄43～70岁[平均(55.2±12.2)岁]。4例肿块位于右侧乳房,1例位于左侧乳房,大小0.65～3.90cm[平均(2.04±1.17)cm]。5例肿块超声为不均匀低回声,4例形态不规则,1例为圆形;4例边界清晰,1例边界模糊;其中2例有钙化,超声表现为点状强回声。彩色多普勒血流显像示肿块3例血流丰富,1例未见明确血流。病理:大体形态学均表现为实性肿物、颜色灰白,边界尚清。结论乳腺神经内分泌癌超声表现有一定的特征性,声像图表现为不均质低回声实性肿块,形态不规则,边界清晰,血流丰富。