Recent developments in the histological diagnosis of spindle cell carcinoma, fibromatosis and phyllodes tumour of the breast

This article reviews recent advances in the diagnosis of these three unusual tumours of the breast. Spindle cell carcinoma needs to be considered in the differential diagnosis of many mammary spindle cell lesions: it is important to be aware of the wide range of appearances, including the recently described fibromatosis-like variant. Immunohistochemistry using a broad panel of cytokeratin antibodies is needed to exclude spindle cell carcinoma; there is frequent expression of basal cytokeratins and p63. CD34 is often expressed by the stroma of phyllodes tumours, but does not appear to be expressed by spindle cell carcinoma or fibromatosis. Nuclear β-catenin is found in about 80% of fibromatoses, but can also be seen in spindle cell carcinomas and phyllodes tumours. Two recent studies have described features useful in the distinction of phyllodes tumour and fibroadenoma on core biopsy, including increased cellularity, mitoses and overgrowth of the stroma, adipose tissue in the stroma and fragmentation of the biopsy specimen. Periductal stromal tumour is a recently described biphasic tumour composed of spindle cells around open tubules or ducts (but no leaf-like architecture) with frequent CD34 expression. The overlap of morphology with phyllodes tumour suggests that it may be best regarded as a variant of phyllodes tumour.     

Postoperative spindle cell nodule of the breast: Pseudosarcomatous myofibroblastic proliferation following endo‐surgery

Despite the frequent use of fine‐needle aspiration, core biopsy and surgery, postoperative spindle cell nodule (PSCN) is a rare pathological complication that may be diagnostically treacherous. Presented herein is the case of a 52‐year‐old woman who developed a 7 mm mammary nodular lesion 66 days after removal of an area of columnar cell hyperplasia involving cellular and architectural atypia, performed with the Mammotome Breast Biopsy System. The lesion was highly cellular and composed of intersecting fascicles of plump spindle cells with blunt‐ended elongated nuclei and nucleoli easily visible. Interspersed mononuclear cells and hemosiderin‐laden macrophages were evident. PSCN is a reactive, benign myofibroblastic proliferation. Differential diagnosis includes benign and malignant spindle cell lesions of the breast. Recognition of this reactive lesion will avoid overdiagnosis of spindle cell malignant tumor. Attention to clinicopathological and histological features should result in accurate recognition of this lesion.     

Benign spindle cell tumor of the male breast

Benign spindle cell tumors of the male breast are definitely rare. They have a subareolar localization and are circumscribed but not encapsulated. Ultrastructurally the neoplasm consists of histiocytic cells, fibroblasts, myofibroblasts and their transitional stages. Myoepithelial cells or smooth muscle cells are lacking. Although myofibroblasts contain lots of filaments, aniline reaction, PTAH stain and iron hematoxylin impregnation remain negative.     

Challenging breast lesions: pitfalls and limitations of fine-needle aspiration and the role of core biopsy in specific lesions

Core biopsy rapidly replaced fine needle aspiration (FNA) over the past decade in evaluation of diseases of the female breast in many centers in the USA. We continue to heavily utilize FNA for the initial evaluation of breast masses in our institution. In this article, we discuss the cytologic and core biopsy findings in challenging breast lesions such as papillary and mucinous proliferations, fibroepithelial neoplasms, and low grade cancers. We specifically focus on the pitfalls and limitations of both diagnostic modalities in these selected specific lesions.     

乳腺纤维瘤病样梭形细胞癌临床病理分析

目的 探讨乳腺纤维瘤病样梭形细胞癌（fibromatosis-like spindle cell carcinoma,FLSCC）临床病理特征。方法 对3例FLSCC病例进行光镜观察和免疫组化染色[CK、CK（34βE12）、vimentin、SMA、ER、PR、Ki-67、c-erbB-2]。结果 3例均为女性,年龄分别为47、53、56岁,均可触及乳腺肿块。肿瘤境界清楚,但镜下边缘呈浸润性。肿瘤主要是梭形细胞、多边形细胞、少量的管状腺体及鳞上皮巢混合,间质纤维明显增生伴胶原化,细胞成束状排列或散在分布,似纤维瘤病样改变。梭形细胞分化良好,异型性不明显,部分区域细胞较丰富,其间聚集的上皮簇或片状多边形细胞核有轻度异型,可见少数核分裂象。多边形细胞与梭形细胞有移行。病变中亦可见淋巴细胞、浆细胞聚集浸润。上皮细胞、多边形细胞及部分梭形细胞CK（34βE12）、CK（AE1／AE3）阳性,CK阴性的梭形细胞表达vimentin、SMA。3例均行肿块切除,其中1例,术后4个月复发,再行乳腺根治术。结论 乳腺（纤维瘤病样）梭形细胞癌是一种少见的、低度恶性肿瘤,诊断需依赖免疫组化标记并与乳腺其它梭形细胞肿瘤相鉴别。     

乳腺伴梭形细胞化生腺癌2例及文献复习

目的 探讨乳腺伴梭形细胞化生腺癌的临床病理特点及鉴别诊断要点。方法 复习2例乳腺伴梭形细胞化生腺癌的临床资料,并行免疫组化标记。结果 组织学特点：癌组织由梭形细胞构成,细胞异型不明显,核分裂象不多,呈片巢状、条索状、编织状排列,梭形细胞内可见腺癌的管状成分。免疫组化染色显示：癌细胞呈上皮性免疫表型,CK(pan)、EMA阳性,ER、PR、C—erbB-2常阴性,不表达S-100蛋白、desmin和vimentin。结论 乳腺伴梭形细胞分化的腺癌是上皮性特殊性乳腺癌中乳腺化生性癌的1种,其诊断主要依靠组织病理学及免疫组化标记。     

The mucinous variant of columnar cell lesions

Verschuur‐Maes A H J & Van Diest P J
(2011) Histopathology  58 , 847–853
The mucinous variant of columnar cell lesions Aims: Mucin‐producing columnar cell lesions (CCL) are a rare, new entity in the breast. The aim of this study was to describe the incidence and follow‐up of mucinous CCLs. Methods and results: Of 4164 breast core needle biopsies (CNBs), 291 showed a CCL and 21 atypical ductal hyperplasia (ADH) originating in a CCL (ADH‐CCL). Mucin production was present in 17 of 291 (5.8%) CCLs and three of 21 (14.3%) ADH‐CCLs, together concerning 0.5% of all CNBs. The most common mucinous CCL pattern was a columnar cell change without atypia, and almost all were detected with microcalcifications as an abnormality at mammography. During a median follow‐up of 3.1 years, no invasive carcinoma or ductal carcinoma in situ was detected. MUC2 was expressed in intraluminal mucin in 12 of 15 (80%) mucinous CCLs, and showed cytoplasmic expression in five of 15 (33%) mucinous CCLs seen in CNBs. Moreover, mucinous CCLs were significantly more common in association with 46 mucinous carcinomas than in 46 ductal carcinomas (28% versus 9%). Conclusions: Mucinous CCLs are rare lesions, with an incidence of about 0.5% in breast CNBs, usually presenting with microcalcifications. Although these lesions might play a role in the mucinous progression spectrum, the short‐term risk of progression to more advanced lesions seems to be low.     

Comparison of fine-needle aspiration cytology and core biopsy for diagnosis of breast cancer

Both fine-needle aspiration (FNA) cytology and core biopsy are useful in the diagnosis of breast cancer. In order to compare the sensitivities of these procedures, we reviewed 209 patients with breast cancer who had either FNA, core biopsy, or both, and also either mastectomy or lumpectomy. Sensitivities for FNA and core biopsies for diagnosing breast cancer were calculated and compared. Sensitivity for FNA or core biopsies interpreted as either atypical or malignant was 93.8% for FNA and 90.1% for core biopsy (P > 0.05). Sensitivity for FNA or core biopsies interpreted as malignant was 65.4% for FNA and 88.7% for core biopsy (P < 0.0001). Sensitivities of FNA interpreted as either atypical or malignant were 92.4% for FNA performed by pathologists and 100% for FNA by nonpathologists (P > 0.05). Sensitivities of FNA interpreted as malignant were 75.8% for FNA by pathologists and 20.0% for FNA by nonpathologists (P < 0.00001). Both FNA and core biopsies are sensitive procedures for the detection of breast cancer. There was no significant difference between sensitivity of FNA and core biopsies interpreted as either atypia or malignancy, although the sensitivity of core biopsies interpreted as unequivocal malignancy was greater than that of FNA. FNAs performed by pathologists were more sensitive than FNAs performed by nonpathologists in making an unequivocal diagnosis of breast cancer.     

Spindle-cell lesions of the liver: diagnosis by fine-needle aspiration biopsy

Rarely, spindle-cell lesions in liver fine-needle aspiration biopsies (FNABs) are encountered. A retrospective review of our experience with lesions that are mesenchymal in origin or appearance was undertaken to elucidate the frequency and spectrum of these lesions. Image-guided liver FNABs performed over a 3-year period (n = 585) at our institution (1996-1998) were retrospectively evaluated. Cytologic smears, cell block preparations, and clinical follow-up of lesions with spindle-cell morphology were reviewed. Twenty-nine of 585 cases were of spindle-cell morphology (5%). Hemangiomas (n = 12, 41%) and metastatic sarcomas (n = 6, 21%) comprised the largest categories, followed by granulomatous inflammation (n = 3, 10%). Other cases included primary angiosarcoma and fibrolamellar hepatocellular carcinoma. The most frequent spindle-cell liver lesion encountered is hemangioma, followed by metastatic leiomyosarcoma and granulomatous hepatitis. Awareness of diagnostic possibilities, special attention to specimen adequacy, and use of ancillary procedures can maximize diagnostic yield.     

SYT在诊断单相纤维型滑膜肉瘤中的价值

目的 探讨SYT在单相纤维型滑膜肉瘤(monophasic fibrous synovial sarcoma,MFSS)的诊断及与其它梭形细胞肿瘤鉴别诊断中的作用.方法 收集MFSS 36例、其它梭形细胞肿瘤32例,其中包括恶性外周神经鞘膜瘤7例、纤维肉瘤6例、平滑肌肉瘤4例、恶性纤维组织细胞瘤7例和孤立性纤维性肿瘤8例,检测sYT蛋白在上述病例中的表达.结果 SYT在MFSS中的阳性表达率为91.67%(33/36),其中15例呈弥漫强阳性表达(>80%的瘤细胞核呈强阳性),12例呈不同程度的阳性表达,50%～80%的瘤细胞核呈强阳性表达.SYT在其他梭形细胞间叶肿瘤中的阳性表达率为59.37%(19/32),其中6例呈弥漫强阳性表达(>80%的瘤细胞核呈强阳性),7例呈不同程度的阳性表达,50%～80%的瘤细胞核呈强阳性.结论 SYT蛋白在MFSS和其他梭形细胞肿瘤中均有较强的阳性表达,提示SYT抗体在MFSS与其他梭形细胞肿瘤的鉴别诊断中作用有限.     

Ductal carcinoma in situ with spindle cells: a potential diagnostic pitfall in the evaluation of breast lesions

AIMS: To evaluate the morphological features of 11 cases of breast ductal carcinoma in situ (DCIS) with spindle cells and to propose an approach to distinguish it from benign mimics. The association with neuroendocrine differentiation was also investigated. METHODS: Cases of breast DCIS with a spindle cell component diagnosed in the Department of Pathology, Singapore General Hospital, between June 1996 and January 2003, were included in the study. The histological characteristics were documented, and immunohistochemistry for neuroendocrine markers, hormone receptors, cerbB2, smooth muscle actin (SMA) and high-molecular-weight (HMW) cytokeratins, was carried out. Electron microscopy was carried out on reprocessed paraffin-embedded material in three cases. RESULTS: Of 11 women diagnosed with DCIS with spindle cells, four presented with nipple discharge, six with a breast lump, while one was discovered to have a screen detected density. The tumour size ranged from 3 to 41 mm. The proportion of spindle cells varied from 10% to 80% of the in-situ tumour cell population. Nuclear grade was low in seven cases and intermediate in four. Necrosis was observed in two cases. Architectural pattern was papillary in six cases, and mixed in the rest. Microinvasion was present in two cases, with possible microinvasion in another two. Immunohistochemistry for neuroendocrine markers synaptophysin and chromogranin showed positive reactivity for at least one marker in all but three cases; one of these latter cases demonstrated ultrastructural neurosecretory granules. Oestrogen and progesterone receptors were expressed in 10 and nine cases, respectively, while cerbB2 was positive in only one case. HMW cytokeratin immunoprofile revealed a general lack of immunostaining within the abnormal cell population; likewise, no positivity for SMA of the cellular proliferation was detected. CONCLUSIONS: Almost all DCIS lesions with spindle cells disclose neuroendocrine differentiation. Although the distinction from benign florid usual hyperplasia may pose a diagnostic histological problem, the presence of diffuse neuroendocrine expression, in conjunction with the pattern of HMW keratin profile on immunohistochemistry, supports an in-situ neoplastic process. The absence of SMA immunostaining, in conjunction with negative reactivity for cytokeratins 5/6 and 14, makes the possibility of a myoepithelial proliferation unlikely.     

Differential diagnosis of spindle cell tumours by electron microscopy—personal experience and a review

Electron microscopy has its value and its limitations in refining the histogenetic diagnosis of certain spindle cell tumours. The ultrastructural diagnostic features of neural tumours, muscle tumours, fibrous histiocytomas, fibrosarcomas, monophasic synovial sarcoma and spindle-cell squamous carcinoma are reviewed and illustrated.     

Fine-needle aspiration cytology vs. core biopsy in the diagnosis of breast lesions

Fine-needle aspiration cytology (FNAC) is an established, highly accurate method for diagnosing breast lesions. However, in recent years there has been increased use of core biopsy (CB) in this setting. The aim of this study was to evaluate the accuracy of FNAC and compare the quality assessment parameters of FNAC and CB in palpable and nonpalpable breast lesions. Data regarding FNAC, CB, and excision biopsy (EB) diagnoses were retrieved from the archives of our department. A total of 4,367 FNAC samples from the years 1999-2001 was reviewed. Of these, corresponding histology results were available for 1,275 lesions, of which 1,248 were primary breast epithelial lesions (788 EB, 199 CB, 261 EB+CB). All cases were analyzed for sensitivity and specificity of FNAC. Cases with both FNAC and CB were compared and quality assessment parameters were calculated using the methodology detailed in the National Health Service Breast Screening Program guidelines. High specificity and sensitivity, as calculated for satisfactory specimens, were achieved with the use of both FNAC and CB. False-positive and false-negative diagnoses were seen in 7/404 (1.7%) and 45/635 (7.1%) of biopsy-proven specimens sampled by FNAC. The corresponding values for CB were 0% and 5.7%, respectively. Inadequate sampling (15.1%) with use of FNAC was particularly seen in collagenous lesions and in submitted specimens sampled by physicians lacking experience with the FNAC procedure. FNAC is a valuable method, although moderately less sensitive than CB. CB is the preferred method for preoperative diagnosis when sampling FNAC provides scarce material and suspicion of a fibrotic and collagenous lesion such as lobular carcinoma and radial scar arises. FNAC is most accurate when experienced cytologists are available and when immediate assessment by professionals is performed for evaluation of material adequacy, so that additional aspirations can be done when needed.     

Pathological criteria and practical issues in papillary lesions of the breast – a review

Papillary lesions of the breast include a broad spectrum of lesions, ranging from benign papilloma, papilloma with atypical ductal hyperplasia (ADH) or ductal carcinoma in situ (DCIS) to papillary carcinoma. The accurate diagnosis of mammary papillary lesions is a challenge for pathologists, owing to the overlapping features among these lesions. In this review, some of the diagnostic criteria of papillary lesions are discussed, with special emphasis on some key morphological features, namely fibrovascular cores, epithelial proliferation in a solid pattern, intraductal papilloma complicated by ADH or DCIS, and invasion and its mimics. The roles of immunohistochemistry, and the interpretation of myoepithelial cell markers, hormone receptors, and high molecular weight cytokeratin, are addressed. Finally, novel biomarkers and genetic aberrations in papillary lesions are summarized.     

麦默通微创旋切系统在乳腺肿块中的应用

目的探讨麦默通微创旋切系统在乳腺肿块中的临床应用效果。方法收集我科2011年9月至2013年5月192例患者318个乳腺肿块行麦默通手术的临床资料,总结其临床使用的经验。结果 318个乳腺肿块中316个肿块被安全切除,术后出现血肿17例,皮下瘀斑8例,均无肿瘤残留与复发。结论麦默通微创旋切系统在乳腺疾病的治疗中具有定位准确、创伤小、安全以及术后美观等优点。     

Histological precision of stereotactic core biopsy in diagnosis of malignant and premalignant breast lesions

The reliability of stereotactic core biopsy in the diagnosis of malignant and premalignant breast lesions was assessed in comparison to excision biopsy in patients with non-palpable suspicious breast lesions detected in a mammography breast screening programme. Fifty-two cases of malignancy and nine of atypical ductal hyperplasia were diagnosed on the programme during the two year period July 1993 to June 1995; two patients did not have excision biopsy. Stereotactic core biopsies and representative sections from 59 excision specimens from the same patients were assessed ‘blind’ by one pathologist. All 51 cancers diagnosed on stereotactic core biopsy were confirmed to be malignant on excision biopsy. There was 96% concordance between stereotactic core biopsy and excision biopsy for the diagnosis of invasive or in situ cancer, and 78% concordance for the type of cancer. The stereotactic core biopsy and excision biopsy diagnoses were: invasive ductal carcinomas (39 on stereotactic core biopsy vs. 33 on excision biopsy), mucinous carcinomas (1 vs. 2), invasive lobular carcinomas (3 vs. 8), and in situ carcinomas (8 vs. 8), two of which had invasive cancer present only in the stereotactic core biopsy. Of the nine cases of atypical ductal hyperplasia diagnosed on stereotactic core biopsy, eight had an excision biopsy, six showed low nuclear grade in situ or invasive cancer, one had a 3mm focus of high grade invasive ductal cancer and one was atypical ductal hyperplasia. In the invasive ductal carcinoma group stereotactic core biopsy underestimated tumour grade: in nine cases (31%) the cancer at excision was of a higher grade. Stereotactic core biopsy is a reliable alternative to excision biopsy in the diagnosis of breast cancer, however, stereotactic core biopsy may underestimate tumour grade in invasive ductal carcinoma and may not differentiate between invasive ductal carcinoma and lobular carcinoma. It is recommended that the diagnosis of atypical ductal hyperplasia on stereotactic core biopsy be followed by excision biopsy, as stereotactic core biopsy underestimates the presence of cancer in this group.