��High-grade�� central acellular carcinoma and matrix-producing carcinoma of the breast: correlation between ultrasonographic findings and pathological features

High-grade carcinoma with a large central acellular zone (central acellular carcinoma, CAC) and matrixproducing carcinoma (MPC) are aggressive tumors that both have a central myxomatous acellular zone. Their characteristic morphology may be useful in diagnostic imaging. Ultrasonographic findings based on the Breast Imaging Recording and Data System (BI-RADS) and detailed histological features were evaluated in 11 cases of CAC and 2 cases of MPC to characterize their features. Safranin-O staining was undertaken for the evaluation of central acellular zones in these tumors. Overall, ultrasonography demonstrated heterogeneous hyperechoic lesions in the center of the hypoechoic mass. Posterior echo enhancement was observed in all but 1 case. One case was classified as malignant and the others as "borderline." Histologically, cancer tissue was located in the periphery of the tumor with a ring-like structure and fewer cellular central areas comprising hyaline cartilage myxoid material such as those stained by safranin-O. The present study showed that the pathological findings of CACs and MPCs accurately reflect the ultrasonographic findings. Tumors that showed hyperechoic areas in the center of the hypoechoic mass, with posterior echo enhancement indicating acellular zones composed by myxochondroid material, and that were also relatively round on ultrasonography may be benign, but evaluation is required to exclude CAC and MPC.     

Histological differences between invasive ductal carcinoma with a large central acellular zone and matrix-producing carcinoma of the breast

Carcinoma with a large central acellular zone (central acellular carcinoma, CAC) and matrix-producing carcinoma (MPC) have been recently noted as basal-like-type breast cancers, but the two entities are often confused. To clarify their histological differences, the histopathological sections of 15 CAC and seven MPC were examined and the following features were compared by reviewing slides: (i) mode of invasion; (ii) alteration of cancer cell adhesion in the transitional area between cellular and acellular zones; (iii) staining of the stromal matrix; (iv) lymphocyte infiltration; and (v) tumor grade. Complete agreement was required between two observers for the assessments of these features. All CAC had relatively sharp margins but showed infiltrative growth accompanied by eosinophilic intercellular matrix. In CAC there was abrupt transition between peripheral cellular and central acellular zones without alteration of cancer cell adhesion. In contrast, all MPC showed expansive growth with a well circumscribed margin, accompanied by basophilic and myxoid intercellular matrix. In MPC there was gradual transition from cellular to acellular areas with gradual loss of cancer cell adhesion. Histological grade 3 and peripheral lymphocyte infiltration were common features. It is suggested that CAC and MPC are histologically distinct entities, and that the aforementioned features are helpful for differential diagnosis.     

Clinicopathological study of invasive ductal carcinoma with large central acellular zone: special reference to magnetic resonance imaging findings

Invasive ductal carcinoma (IDC) with central acellular zone is sometimes encountered, but its clinicopathological features have not yet been fully investigated. The clinicopathological features of 10 resected cases of IDC with a large central acellular zone were investigated. The tumor size ranged from 6 to 28 mm with a mean of 14.3 +/- 6.9 mm. Contrast-enhanced magnetic resonance imaging (MRI) showed a ring-like appearance in the tumor. Sagittal fat-suppressed T2-weighted MRI had very high to intermediate signal intensity in a central area. Histologically, cancer tissue was located in the periphery of the tumor with a ring-like pattern and a large central area was occupied by acellular amorphous tissue that was strongly stained by alcian blue. Lymph vessel permeation was seen in eight cases. Among the tumors with focal enhancement in the central areas >1 cm in diameter on contrast MRI, marked increase of microvessel was observed in the enhanced spot. The mean of p53 and Ki-67 labeling indices was 56.2% and 36.3%, respectively. IDC with a large central acellular zone presenting with characteristic MRI should be noted as a new morphological entity.     

Prevalent and up‐regulated vimentin expression in micropapillary components of lung adenocarcinomas and its adverse prognostic significance

The factors conferring the increased malignancy on lung adenocarcinoma with micropapillary component (AC‐MPC) remain to be elucidated. On proteomics based on 2‐dimensional gel electrophoresis, 19 proteins differentially expressed by more than 1.5‐fold between AC‐MPC and conventional adenocarcinoma (CAC); in particular, vimentin, one of the proteins, was 3.5‐fold up‐regulated in AC‐MPC. Subsequent semi‐quantitative investigation by immunohistochemistry with large cohorts comprised 101 AC‐MPC and 119 CAC, respectively, of different stages revealed that vimentin was expressed in MPC of 95 (94.1%) AC‐MPC and the expression scores were higher than those of well‐ and moderately differentiated CAC, as well as the background non‐MPC of the AC‐MPC (P < 0.0001), but not significantly different from those of poorly differentiated CAC (P = 0.561). Even within the AC‐MPC entity, higher vimentin expression was correlated with more frequent vascular invasion and more advanced node metastasis (P < 0.02), and multivariate analysis showed that high vimentin expression and worse node statuses were independent indicators of adverse prognosis (P < 0.048). In conclusion, vimentin expression is prevalent and markedly up‐regulated in MPC, which might reflect the biological essence of poorer differentiation or dedifferentiation of MPC, and this might have a role in the acquisition and increase of invasiveness and consequent more malignant nature of MPC.     

Metaplastic carcinomas of the breast. I. Matrix-producing carcinoma

The clinical and pathologic features of 26 examples of a histopathologically distinct form of metaplastic carcinoma of the breast are reported. All neoplasms had overt carcinoma with direct transition to a cartilaginous and/or osseous stromal matrix without an intervening spindle cell zone or osteoclastic giant cells. Therefore, we designate this distinctive form of metaplastic carcinoma as "matrix-producing carcinoma" (MPC). All patients were women, the average age was 58 years, and all patients were eligible for a minimum of 5 years follow-up (mean follow-up period, 8.6 years). Twenty-three patients were treated by a form of mastectomy and three were treated by local excision. The 5-year survival rate for patients following mastectomy or partial mastectomy was 70%, contrasted with 50% for patients treated by local excision. The cumulative 5-year survival rate for MPC was 68%. All of the nine lesions that recurred did so within 2.5 years of initial therapy. Eight of these patients (89%) died from tumor within 4 years of initial therapy. The ninth was alive at last contract. Radiation and chemotherapy were of limited effectiveness. Significant features of the neoplasm associated with progression were large size, diffuse cellularity of the stromal matrix, and atypical cartilaginous metaplasia. Ultrastructural examination of one case and immunohistochemical evaluation of 12 cases revealed MPC to have myoepithelial characteristics.     

Cytokeratin 8 immunostaining pattern and E-cadherin expression distinguish lobular from ductal breast carcinoma

Immunohistochemistry using antibodies to cytokeratin 8 can serve as a valuable diagnostic tool for the differentiation of lobular from ductal carcinomas of the breast. In contrast with ductal carcinomas, which exhibit a peripheral-predominant immunostaining pattern, adjacent tumor cells "molding" to each other, lobular carcinomas exhibit a ring-like perinuclear immunostaining pattern, creating a "bag of marbles" appearance with neighboring tumor cells. This immunostaining pattern is stable even in the tumors that otherwise do not exhibit characteristic histomorphologic features (i.e., solid or pleomorphic type of a lobular carcinoma) and tumors that mimic growth patterns characteristic of the respective other tumor type (i.e., targetoid or single-file growth pattern in a ductal carcinoma). Furthermore, we demonstrate that ductal carcinomas express E-cadherin in a similar peripheral-predominant immunostaining pattern (33/33 cases), while all 15 lobular carcinomas were negative for E-cadherin, suggesting a role for E-cadherin in the architectural organization of the cytoskeletal scaffolding within the tumor cells.     

Micropapillary adenocarcinoma of lung: Morphological criteria and diagnostic reproducibility among pulmonary pathologists

ContextInvasive micropapillary adenocarcinoma (MPC) is an aggressive variant of lung adenocarcinoma, frequently manifesting with advanced stage lymph node metastasis and decreased survival.ObjectiveIdentification of this morphology is important, as it is strongly correlated with poor prognosis regardless of the amount of MPC component. To date, no study has investigated the morphological criteria used to objectively diagnose it.DesignHerein, we selected 30 cases of potential MPC of lung, and distributed 2 digital images per case among 15 pulmonary pathology experts. Reviewers were requested to diagnostically interpret, assign the percentage of MPC component, and record the morphological features they identified. The noted features included: columnar cells, elongated slender cell nests, extensive stromal retraction, lumen formation with internal epithelial tufting, epithelial signet ring-like forms, intracytoplasmic vacuolization, multiple nests in the same alveolar space, back-to-back lacunar spaces, epithelial nest anastomosis, marked pleomorphism, peripherally oriented nuclei, randomly distributed nuclei, small/medium/large tumor nest size, fibrovascular cores, and spread through air-spaces (STAS).ResultsCluster analysis revealed three subgroups with the following diagnoses: “MPC”, “combined papillary and MPC”, and “others”. The subgroups correlated with the reported median percentage of MPC. Intracytoplasmic vacuolization, epithelial nest anastomosis/confluence, multiple nests in the same alveolar space, and small/medium tumor nest size were the most common criteria identified in the cases diagnosed as MPC. Peripherally oriented nuclei and epithelial signet ring-like forms were frequently identified in both the “MPC” and “combined papillary and MPC” groups.ConclusionsOur study provides objective diagnostic criteria to diagnose MPC of lung.     

Immunohistochemical study of metaplastic carcinoma and central acellular carcinoma of the breast: central acellular carcinoma is related to metaplastic carcinoma

Metaplastic breast cancers (MBCs) [spindle cell carcinoma (SpCC), squamous cell carcinoma (SCC), and matrix-producing carcinoma (MPC)] and invasive carcinomas with central acellular zones (CACs) were analyzed with respect to biological potential by immunohistochemical analyses. Specimens from 40 patients [20 with MBCs (7 with SCC, 6 with SpCC, 5 with MPC, and 2 with mixed type)] and 20 with CACs were analyzed using antibodies to cytokeratin (CK) 8, 5/6, 14, AE1/AE3, 34αE12, involucrin, c-kit, vimentin (VIM), alpha-smooth muscle actin, p63, epidermal growth factor receptor, epithelial cell adhesion molecule, and estrogen receptor (ER)/progesterone receptor (PR)/HER2. Expression of CK5/6, 34βE12, VIM, nuclear p63, and cytoplasmic p63 was significantly higher with MBCs than CACs (38%/13%, 70%/43%, 85%/33%, 68%/40%, and 48%/18%, respectively). Other markers were expressed at various levels in these tumors, but the difference between them was not significant. Eighteen MBC and 8 CAC cases were triple (ER/PR/HER2) negative; 17 MBCs and 7 CACs were basal-like tumors. Several differences were seen in MBCs and CACs, but they were heterogeneous, differentiating multipotentially into mesenchymal, myoepithelial, basal-like phenotypes with "stem cell-like" features. Thus, CACs are related to MBCs by immunohistochemical analyses as well as according to morphological findings.     

Diffuse neuroendocrine differentiation in a morphologically composite mammary infiltrating ductal carcinoma: a case report and review of the literature

Neuroendocrine differentiation has been reported in both in situ and infiltrating breast cancers. The prognostic significance of neuroendocrine differentiation in mammary carcinoma is unclear. We report a case of infiltrating ductal carcinoma in which there was a morphologically conventional-appearing infiltrating ductal component admixed with nests of cells that resembled a carcinoid tumor and initially mimicked the appearance of intraductal carcinoma. Immunohistochemical stains for synaptophysin and chromogranin demonstrated diffuse, strong positivity uniformly throughout the tumor, even in the more conventional-appearing areas. Electron microscopic examination of tissue retrieved from paraffin blocks was attempted unsuccessfully. We concluded that this was an infiltrating ductal carcinoma with morphologic and immunohistochemical evidence of neuroendocrine differentiation. The case is discussed with a review of the literature and a discussion of nomenclature for tumors of the breast showing variable degrees of neuroendocrine differentiation.     

Analysis of multiple primary cancer autopsy cases associated with breast cancer: 2002–2010

Breast cancer patients have a generally increased risk of developing second cancers. The object of this study was to clarify the increased as well as decreased incidence of cancers in breast cancer patients using autopsy cases. 164 211 autopsy cases in the Annual of Pathological Autopsy Cases in Japan from 2002 to 2010 were analyzed for multiple primary cancer (MPC). Female MPC cases (4222 cases) were selected. We investigated the cancer incidence observed in breast cancer associated MPC. The Chi‐squared test was used for analysis. All P‐values were two‐sided, and differences at P < 0.05 were considered significant. Breast cancer associated MPC showed a significantly increased incidence of ovarian, pancreatic, and skin cancer (Odds Ratio [95 % confidence interval (CI)]) = 1.464 [1.03, 2.08], 1.414 [1.08, 1.85] and 2.092 [1.28, 3.41]), and a decreased incidence of colorectal and cervical cancer (OR [95 % CI]) = 0.732 [0.60, 0.90], 0.605 [0.38, 0.96]). Our findings of an increased incidence of malignancies in breast cancer associated MPC cases were consistent with the results of previous population‐based studies. This study is the first study to analyze massive autopsy data on MPC which provide new evidence clinically and pathologically.     

临床A期前列腺癌的病理特征和漏诊误诊原因分析

目的探讨临床A期前列腺癌的病理特征,并分析其好发部位及漏诊误诊原因.方法复查上海地区5所医院1 020份前列腺切除标本,通过免疫组织化学SP法检出50例临床A期前列腺癌,根据肿瘤分化程度及容量分出A1期癌12例和A2期癌38例,比较病理形态差异,分析A1和A2期癌的漏诊误诊原因.结果 A1期癌以低中级别、低容量、多灶性生长为特点,A2期癌以高中级别、高容量、高浸润性伴高级别上皮内新生物为特征.在漏诊误诊的8例A期癌中,A1期癌占7例,均误诊为良性增生性小腺泡病变.A2期癌1例误诊为反应性上皮样组织细胞增生.结论 A1期癌大多在增生的前列腺移行带和中央带组织易被发现,A2期癌可能是大多原发于周围带的高中级别癌浸润至前列腺中央区域.国内A期癌检出率低的原因主要是因为标本取材量少和A1期癌漏诊率较高.     

临床A期前列腺癌的病理特征的漏诊误诊原因分析

目的：探讨临床A期前列腺癌的病理特征,并分析其好发部位及漏诊误诊原因,方法：复查上海地区5年医院1020份前列腺切除标本,通过免疫组织化学SP法检出50例临床A期前列腺癌,根据肿瘤分化程度及容量分出A1期癌12例和A2期癌38例,比较病理形态差异,分析A1和A2期癌的漏诊误诊原因。结果：A1期癌以低中级别,低容量,多灶性生长为特点,A2期癌以高中级别,高容量,高浸润性伴高级别上皮内新生物为特征,在漏诊误诊的8例A期癌中,A1期癌占7例,均误诊为良性增生性小腺泡病变,A2期癌1例误诊为反应上皮样组织细胞增生。结论：A1期癌大多在增生的前列腺移行带和中央带组织易被发现,A2期癌可能是大多原发于周围带的高中级别癌浸润至前列腺中央区域,国内A期癌检出率低的原因主要是因为标本取材量少和A1期癌漏诊率较高。     

Pregnancy-associated breast disease: radiologic features and diagnostic dilemmas

In this paper, we evaluate the radiological features of pregnancy-associated breast lesions and discuss the difficulties in diagnosis by imaging. We selected patients who were diagnosed with pregnancy-associated breast lesions during the previous 5 years. All patients complained of palpable lesions in the breast and underwent ultrasonographic (US) examination, the first choice for examination of pregnancy-related breast lesions. Any suspicious lesions found by the US were recommended for a US-guided core biopsy, US-guided fine needle aspiration (FNA), or surgery. Various breast lesions were detected during pregnancy and lactation, including breast cancer, mastitis and abscesses, lactating adenoma, galactoceles, lobular hyperplasia, and fibroadenomas. The imaging features of pregnancy-associated breast lesions did not differ from the features of non-pregnancy-associated breast lesions; however, some pregnancy-associated benign lesions had suspicious sonographic features. A US-guided core biopsy was necessary for differentiating benign from malignant. In patients with breast cancer, the cancer was often advanced at the time of diagnosis. In conclusion, various pregnancy-related breast lesions were detected and the imaging of these lesions had variable findings. Breast ultrasound could be an excellent imaging modality for diagnosis and differentiation between benign and malignant lesions. However, when the imaging results are suspicious, a biopsy should be performed to obtain a pathologic diagnosis.     

Composite type of breast carcinoma with endocrine differentiation: a cytological and immunohistochemical study

We describe a case of breast carcinoma with endocrine differentiation containing a mixture of three different histological features that occurred in a 71-year-old woman. Histologically, the tumor was predominantly intraductal, but slightly invasive. In the intraductal lesion, the tumor consisted mainly of ovoid to round cells with a modest to abundant amount of granular eosinophilic cytoplasm or intracytoplasmic mucin (mucin-producing carcinoma in situ ). It also consisted, in part, of plump spindle cells with scant cytoplasm that contained argyrophilic granules in a trabecular pattern or an arrangement of perivascular pseudorosettes (atypical carcinoid tumor like-features). Mucous lake and tumor cells floating in mucin were seen in the invasive lesion (mucinous carcinoma). Immunohistochemical staining revealed endocrine differentiation of the tumor cells of both intraductal and invasive lesions. These findings suggest that the different histological features derived from pluripotent cells upon endocrine differentiation, and that endocrine differentiation of the tumor cells had already occurred at an earlier stage of carcinogenesis, prior to the appearance of the mucinous carcinoma. Cytologically, plasmacytoid tumor cells appeared in loosely cohesive clusters or as sparsely single cells in a background of a mucinous substance.     

29例甲状腺癌相关异时性多原发癌临床分析

目的 阐述甲状腺癌合并异时性多原发恶性肿瘤临床特点,总结含有甲状腺癌的异时性多原发癌的临床诊治思路.方法 回顾分析2005年8月至2015年8月我院共收治住院甲状腺癌相关的异时性多原发癌29例的临床病理资料.结果 异时性甲状腺多原发癌占同期收治甲状腺癌的2.39%(29/1212).甲状腺癌相关异时性多原发癌另一癌发生在乳腺9例、头颈部7例、肺部5例、消化系统3例、生殖系统2例、甲状腺1例、血液系统1例、泌尿系统1例.29例异时癌中甲状腺癌作为首发癌19例,第二原发癌乳腺癌最多.非甲状腺癌先发首发癌10例,第二原发癌头颈部肿瘤最多.甲状腺癌先发组首发癌与第二原发癌发病间隔时间明显长于非甲状腺癌先发组,有统计学意义.结论 与甲状腺癌相关的异时性多原发癌有一定的临床特点,预后较好.应重视初诊肿瘤患者的随诊工作,早期发现,积极治疗,提高患者生存率.     

Signet ring epithelioid stromal tumor of the small intestine

Cells having a signet ring appearance can occur in mesenchymal, lymphoid, and other nonepithelial neoplasms. We report the case of an intestinal stromal tumor with smooth muscle differentiation and a prominent signet ring cell component. The presence of signet ring forms of smooth muscle cells in sections of paraffin-embedded tissue often contrasts with a lack of cytoplasmic spaces by electron microscopy, and the ultrastructural finding of signet ring-like areas in the present case can be attributed to the fact that the tissue for electron microscopy was retrieved fromparaffin blocks where this peculiar artifact already existed. Ultrastructural examination of the signet ring-like areas suggests that they originated as retraction spaces which may have resulted from variations in intracellular tension forces related to the distribution of actin filaments.     

双环乳晕切口在多中心乳腺良性肿瘤中的应用优势探讨

目的　探讨采用双环乳晕切口在多中心乳腺良性肿瘤临床外科手术中的应用优势。 方法　回顾性分析我院肿瘤外科2016年1月-2017年7月收治的45例行“双环乳晕切口”治疗的“多中心乳腺良性肿瘤”的患者。对所有患者的临床病理因素、手术时间、术中出血量、术后拔管时间、并发症以及术后3个月美容效果、6个月后复发率进行评价。 结果　切除肿瘤数量单侧（5±1）个（2~8个）,双侧（8±2）个（3~13个）。肿瘤长径单侧（5.3±1.3）cm（1.5~8.5 cm）,双侧（3.0±1.5）cm（1.2~6.5 cm）。术中出血量单侧(8.0±2.8)ml（5~15 ml）,双侧(15.4±3.1)ml（10~25 ml）。术后3个月通过门诊和微信随访美容效果,患者满意度在93.3%。术后6个月有37例患者进行彩超复查,其中单侧病变患者22例,复发3例,复发率13.6%;双侧病变患者15例,复发2例,复发率13.3%。 结论　双环乳晕切口在处理分布在不同象限多发性肿瘤、以及有塑形需求的患者人群中具有一定优势。手术安全性高,操作方便,适合临床推广应用。     

基底细胞样型乳腺癌的临床病理观察

目的 观察基底细胞样型乳腺癌(BLBC)的临床病理特征.方法 采用ER、PR、HER2、Ki-67、CK5/6、CK14和表皮生长因子受体(EGFR)进行免疫组织化学EnVision法检测458例女性浸润性乳腺癌以筛选BLBC,比较BLBC与其他免疫表型乳腺癌的临床病理特征.对其中228例浸润性乳腺癌患者进行了随访.结果 458例浸润性乳腺癌中发现BLBC 46例(10.0%).癌灶直径平均3.3 cm.58.7%(27/46)出现推挤性生长方式,52.2%(24/46)出现地图状坏死,30.4%(14/46)癌灶中心出现无细胞纤维化区域以及63.0%(29/46)癌灶周边和间质内有不同程度淋巴细胞浸润.癌细胞异型性明显,核分裂象多见,主要排列成不规则、紧密实性结构.Ki-67高表达(>25%)在BLBC中占43.5%(20/46).CK5/6、CK14和EGFR阳性分别见于58.7%(27/46)、43.5%(20/46)和65.2%(30/46)的BLBC病例.BLBC的3年累积生存率为66.9%,低于管腔A型乳腺癌,与HER2高表达型乳腺癌差异无统计学意义.结论 BLBC在女性浸润性乳腺癌中所占比例为10%,其组织结构和细胞形态具有一定特征性,但诊断BLBC仍必需结合其免疫表型.BLBC是预后比较差的乳腺癌亚型之一.     

Pathologic features of breast cancers in women with previous benign breast disease

To compare pathologic features of the cancers arising after different types of benign breast disease (BBD), we reviewed the invasive breast cancer slides of 169 women with a previous benign biopsy result. Lesions were categorized previously as nonproliferative, proliferative without atypia, or atypical hyperplasia. Pathologic features of the cancers were evaluated without knowledge of the previous BBD category. Estrogen and progesterone receptor immunohistochemistry was performed on available tissue blocks. The median times between a benign result and cancer were 100, 124, and 92 months for women with nonproliferative lesions, proliferative lesions without atypia, and atypical hyperplasia, respectively. Cancers in the 3 groups did not differ significantly in tumor size, axillary lymph node status, or histologic grade, and there was no significant difference in the distribution of histologic types of breast cancer. Lymphatic vessel invasion, extensive intraductal component, and hormone receptor status did not differ among BBD categories. The pathologic features of breast cancers that develop in women with a previous benign biopsy result do not vary according to the histologic category of the previous BBD.