Elastosis in the male breast

Elastosis, a common finding in infiltrating ductal and lobular carcinomas of the female breast, has also been described in a variety of other benign and malignant lesions. However, elastosis has not been previously documented in male breast lesions. Ten cases of gynaecomastia and five neoplastic lesions of the male breast were evaluated for elastosis. In gynaecomastia, elastosis is a feature of the ducts surrounded by collagenized fibrous tissue but not of ducts with loose connective tissue stroma. This association is also evident to some extent in neoplastic lesions. These findings suggest that elastosis is an expression of periductal fibrosis irrespective of the nature of the lesion.     

Minute pancreatic adenocarcinoma presenting with stenosis of the main pancreatic duct

We describe a case of minute pancreatic ductal adenocarcinoma featuring stenosis of the main pancreatic duct (MPD) and associated with histological findings of periductal elastosis and fibroblast proliferation. A 53-year-old Japanese man with preoperative radiological evidence of MPD stricture and dilation of the distal MPD, and suspected of having pancreatic cancer, underwent successful resection. Neither radiological nor macroscopic examination directly disclosed any tumorous lesions, and a small focus of carcinoma (8 x 8 mm) was only revealed on microscopic examination. The tumor was a poorly differentiated, invasive ductal adenocarcinoma that had invaded the intrapancreatic nerves and veins. Interestingly, the MPD located at the edges of the tumor had not been destroyed by the carcinoma, but its wall had been thickened by elastic tissue and fibroblast proliferation, resulting in stenosis. The peripheral pancreas exhibited secondary obstructive pancreatitis. To date, the detection of small pancreatic tumor masses using imaging procedures remains difficult, and most patients are diagnosed on the basis of pancreatic ductal changes. However, the published work on small pancreatic cancers contains little information about the histological features of the affected MPD. The present findings suggest that MPD strictures are not always provoked by destruction or filling with cancer cells, and that they can be caused by periductal elastosis and fibroblast proliferation in a minute carcinoma. Such changes in the MPD may therefore be of clinical importance in the detection of early stage cancers.     

Elastosis in breast carcinoma: II. Association of protease inhibitors with immature elastic fibres

The elastosis of 11 invasive ductal and infiltrative lobular carcinomas of the breast was specifically immunostained for the plasma protease inhibitors alpha-1 antitrypsin, alpha-1 antichymotrypsin, alpha-2 macroglobulin, inter alpha trypsin inhibitor and C1 esterase inhibitor. None of these components was detected in the elastic fibres of normal ducts or blood vessels in the breast. The elastosis in breast carcinomas was also stained by Concanavalin A and Triticum vulgaris lectins. Such lectin staining probably represents binding to the microfibrillar component of elastic fibres, which is increased in immature elastic fibres, thus suggesting that the elastotic fibres of breast carcinoma are recently synthesised. It is suggested that the presence of protease inhibitors may influence the metabolism of elastic fibres, facilitating elastic fibre proliferation by the inhibition of elastinolytic enzymes.     

胰腺导管腺癌中胰腺星形细胞的研究进展

胰腺星形细胞(pancreatic stellate cells,PSC)是胰腺导管腺癌(pancreatic ductal adenocarcinoma,PDAC)肿瘤微环境中最重要的成分,在PDAC发生发展中具有非常关键的作用.目前大量研究关注于PSC与胰腺癌细胞(pancreatic cancer cells,PCC)之间的相互作用及PSC在PDAC微环境中发挥的作用.PSC在许多情况下发生活化,如乙醇、氧化应激和高血糖等.PDAC早期即可出现PSC的活化,PCC可以诱导刺激PSC发生活化,活化的PSC可以产生大量胶原纤维,形成适宜PCC生长的间质微环境,促进PCC的增殖,减少化疗药物对肿瘤细胞的杀伤作用.另外,PSC还可以与间质中各种细胞成分如内皮细胞和各种免疫细胞相互作用,在血管生成、免疫逃逸和神经侵犯等方面协助肿瘤进展.因此,阐明PSC与肿瘤细胞以及其他间质成分之间复杂的相互作用至关重要.     

Elastosis in the normal aging breast. A histopathologic study of 140 cases.

The incidence and pattern of elastosis of the breast was studied in tissue specimens taken at autopsy from 140 women with clinically normal breasts, ranging in age from 19 through 101 years. Elastosis, presence of excess elastic fibers, while less common in younger women, may be found in nearly half of all women over age 50 years with no breast disease. Elastosis occurs in three sites: diffusely in the stroma, around vessels, and around ducts. In the first two sites, it bears little relationship to age, while periductal elastic tissue appears to accumulate with age, probably reflecting parity, until about age 50 years. Thereafter, it is found at a more or less constant incidence and degree. While it may be associated with breast cancer, periductal elastosis by itself is not a cause for concern. Marked perivascular elastosis is, however, uncommon at any age, and its presence should suggest a special search for carcinoma, if not already evident.     

Paucicellular infiltrating ductal carcinoma of pancreas: an unusual variant

A 65-year-old man presented with obstructive jaundice from a 3-cm mass in the head of the pancreas. A Whipple resection was performed. Histologic examination of the tumor showed scanty tumor cells arranged in a single-file manner set within a desmoplastic sclerotic stroma. In other areas, the tumor was arranged around preexisting ducts in a targetoid fashion. Very focal ductal and signet-ring cell differentiation was noted. This unusual variant of pancreatic cancer was characterized by paucicellularity and a pattern of invasion resembling lobular carcinoma of breast.     

乳腺癌弹力纤维增生的分布及其意义

应用大切片观察83例乳腺癌间质弹力纤维增生(EL)的形态学,以45例乳腺良性疾病作对照,并与乳腺淋巴巨噬细胞浸润程度,雌激素受体状况以及影响患者预后的有关临床病理因素等进行相关性研究。结果表明:乳腺癌EL发生率为80.7%,分为局灶型和弥漫型两种;EL也可见于乳腺良性疾病,并非仅在乳腺癌出现。乳腺癌EL程度与病理类型有关,并与组织分化程度、雌激素受体状态及间质巨噬细胞浸润程度呈正相关,提示EL属于宿主防御反应的一种形态学表现。     

长链非编码RNA CCHE1在胰腺导管腺癌中的表达及临床意义

目的 检测长链非编码RNA(lncRNA)CCHE1在胰腺导管腺癌(PDAC)细胞和组织中的表达,探讨lncRNA CCHE1与PDAC临床病理特征及预后间的关系.方法 RT-PCR检测PDAC组织及配对癌旁组织以及PDAC细胞和胰腺导管上皮细胞中lncRNA CCHE1的表达;利用单因素方差分析探讨lncRNA CC...     

Usefulness of immunohistochemical staining for MUC5AC in differentiating primary pancreatic cancer from pancreatic metastasis of breast cancer

Diagnosis of pancreatic ductal adenocarcinoma (PDAC) and its differentiation from metastases to the pancreas from other organs remains challenging. We report a case in which immunohistochemical staining for MUC5AC was useful in distinguishing primary pancreatic cancer from breast cancer metastasis. A 51‐year‐old Japanese woman who underwent curative resection of her breast cancer was referred to our hospital with a pancreatic head tumor. Although we surmised her pancreatic tumor to be metastatic breast cancer based on her past history and imaging studies, she was subsequently diagnosed with PDAC on the basis of immunohistochemical staining for MUC5AC using specimens obtained by endoscopic ultrasound‐fine‐needle aspiration. Thus, MUC5AC may be a useful diagnostic marker for discriminating PDAC from a secondary malignancy.     

Stromal Reaction to Neoplasia: Colonic Carcinomas

The stroma and stromal reaction in the normal colon and in 14 different colonic tumors were studied by electron microscopy. Elastosis is a significant part of the stromal reaction to colonic adenocarcinomas and rectal squamous cell carcinomas. Two carcinoid tumors elicited no significant elastosis. In some of the adenocarcinomas, small muscular arteries close to neoplastic tissue developed massive elastosis of the media. This may indicate that the elastosis is due to stimulation of nonneoplastic stromal cells by some unknown neoplastic factor or factors.     

Dysplasia and carcinoma in situ of the pancreatic duct epithelium

Histopathologic aspects of metaplasia, dysplasia and carcinoma in situ of the pancreas are described and diagnostic difficulties discussed. Morphological lesions of the pancreatic ducts were studied in 200 control autopsy cases, and in 85 clinical cases with primary pancreatic carcinoma. The following groups of morphologic lesions can be differentiated with sufficient reliability: normal ductepithelium, metaplasia and hyperplasia; mild and moderate epithelial dysplasia; severe dysplasia including carcinoma in situ; invasive ductal/ductular carcinoma. Important for a reliable diagnosis are good specimens and good histological sections. Severe dysplasia including carcinoma in situ in areas surrounding invasive carcinomas as well as isolated severe dysplasia herald a high risk of progressive tumor disease for the patient.     

Expression of urocortin in pancreatic ductal adenocarcinoma and pancreatic intraepithelial neoplasia

Urocortin (UCN) is a 40‐aminoacid neuropeptide that regulates angiogenesis and inhibits cell proliferation. Our aim was to examine the relationship of UCN expression to the clinicopathological parameters of pancreatic ductal adenocarcinoma (PDAC) and histological grade of pancreatic intraepithelial neoplasia (PanIN). Tissue microarray was used to analyze UCN protein expression in 89 surgical specimens including 21 PanIN, 3 PDAC arising from PanIN, and 65 PDAC without PanIN. UCN immunoscores ranging from 0 to 12 were obtained by multiplying intensity (scored on a 3‐point scale) by the percentage of stained cells (scored on a 4‐point scale). Strong expression of UCN was detected in 5 specimens of non‐neoplastic pancreatic ductal epithelia. UCN immunoscore was significantly higher in PanIN‐1 than in PanIN‐2 and PanIN‐3 (p = 0.038) and significantly higher in well‐differentiated PDAC or early American Joint Committee on Cancer (AJCC) stage PDAC than in poorly differentiated or advanced stage PDAC (p = 0.025, p = 0.018). Higher expression of UCN correlates with PDAC tumor grade and AJCC pathologic stage as well as PanIN grade. Immunohistochemical assessment of UCN may help clinicians predict tumor recurrence rate and help pathologists make a proper diagnosis.     

Stromal Reaction to Neoplasia: Colonic Carcinomas

The stroma and stromal reaction in the normal colon and in 14 different colonic tumors were studied by electron microscopy. Elastosis is a significant part of the stromal reaction to colonic adenocarcinomas and rectal squamous cell carcinomas. Two carcinoid tumors elicited no significant elastosis. In some of the adenocarcinomas, small muscular arteries close to neoplastic tissue developed massive elastosis of the media. This may indicate that the elastosis is due to stimulation of nonneoplastic stromal cells by some unknown neoplastic factor or factors.     

Dopamine-beta-hydroxylase-positive nerves in normal and transplanted pancreatic tissue in the anterior eye-chamber of rats

Dopamine-beta-hydroxylase(DBH)-positive nerves were demonstrated in normal and in pancreatic tissue fragments transplanted for 22 and 32 days into the anterior eye-chamber of rats using immunohistochemical techniques. Dopamine-beta-hydroxylase-immunopositive neurons of different shapes could be observed in normal pancreas. The neurons had either spindle or oval shapes. In the transplanted tissue, DBH-positive neuronal profiles were found in the stroma. In some cases DBH-immunopositive cells appeared as a cluster of cells around pancreatic ducts and blood vessels or as solitary cells. The wall of pancreatic ducts in the transplants also contained DBH-immunopositive nerve profiles.     

CD34+ fibrocytes in neoplastic and inflammatory pancreatic lesions

Besides its function as a matrix-producing cell, the CD34+ fibrocyte has been reported to be an antigen-presenting cell capable of priming naive T cells in situ. Therefore, it has been claimed that the CD34+ fibrocyte may play an important role in host response to tissue damage. The objective of the present study was to analyze the presence and distribution of CD34+ fibrocytes and smooth muscle actin (SMA) reactive myofibroblasts in relation to the underlying pancreatic disease. We investigated a total of 12 pancreatic adenocarcinomas, 7 endocrine tumors of the pancreas, and 8 cases of chronic pancreatitis; in 11 cases, normal pancreatic tissue was available. The stroma of normal pancreatic tissue harbored diffusely scattered CD34+ fibrocytes. Chronic pancreatitis was characterized by an increased number of stromal CD34+ fibrocytes paralleled by a gain of SMA reactive myofibroblasts which were not observed in the normal pancreatic stroma. The stroma of pancreatic ductal adenocarcinomas and endocrine tumors was devoid of CD34+ fibrocytes or showed at least a focal loss of this cell type, whereas SMA reactive myofibroblasts were detected in both endocrine tumors and adenocarcinomas. We conclude that detection of CD34+ fibrocytes may constitute an adjunctive tool in distinguishing chronic pancreatitis from ductal adenocarcinoma since the absence of this cell population strongly favors a neoplastic process. Moreover, CD34+ fibrocytes and myofibroblasts appear to be involved in stromal remodeling associated with chronic pancreatitis and ductal adenocarcinoma.     

Bombesin receptors in distinct tissue compartments of human pancreatic diseases

Overexpression of receptors for regulatory peptides in various human diseases is reportedly of clinical interest. Among these peptides, bombesin and gastrin-releasing peptide (GRP) have been shown to play a physiological and pathophysiological role in pancreatic tissues. Our aim has been to localize bombesin receptors in the human diseased pancreas to identify potential clinical applications of bombesin analogs in this tissue. The presence of bombesin receptor subtypes has been evaluated in specimens of human pancreatic tissues with chronic pancreatitis (n = 23) and ductal pancreatic carcinoma (n = 29) with in vitro receptor autoradiography on tissue sections incubated with 125I-[Tyr4]-bombesin or the universal ligand 125I-[D-Tyr6, beta-Ala11, Phe13, Nle14]-bombesin(6-14) as radioligands and displaced by subtype-selective bombesin receptor agonists and antagonists. GRP receptors were identified in the pancreatic exocrine parenchyma in 17 of 20 cases with chronic pancreatitis. No measurable bombesin receptors were found in the tumor tissue of ductal pancreatic carcinomas, however, GRP receptors were detected in a subset of peritumoral small veins in 19 of 29 samples. Moreover, residual pancreatic islets in these tissues were shown to express the BB3 receptor subtype. These data demonstrate the presence of bombesin receptors in three distinct tissue compartments of the pancreas, namely GRP receptors in the exocrine parenchyma in chronic pancreatitis and in peritumoral vessels around ductal pancreatic carcinomas, and BB3 receptors in residual pancreatic islets. Such a selective expression of bombesin receptor subtypes in pancreatic tissues may not only be of pathophysiological significance but may represent the basis for potential diagnostic and therapeutic clinical applications of bombesin analogs, including GRP receptor scintigraphy to differentiate chronic pancreatitis from ductal pancreatic carcinoma.     

Elastosis in breast carcinoma: I. Immunohistochemical characterization of elastic fibres

Elastosis associated with invasive ductal and lobular carcinomas of the breast was examined by tinctorial and immunohistochemical staining methods, enzyme digestion, and electron microscopy. The elastotic material exhibited the tinctorial staining properties of elastic fibres, and the ultrastructural appearances were those of elastic fibres although there was a higher proportion of microfibrils than in normal mature elastic fibres. The elastosis was immunostained by antisera to human fetal elastin, lysozyme and amyloid P component, as in other sites where elastic fibres are found. These findings indicate that immunohistochemically intact elastic fibres are present in the elastosis of breast cancer. They also demonstrate that lysozyme and amyloid P component are co-distributed with elastic fibres in elastosis of breast carcinoma, as distinct components with different susceptibilities to enzyme digestion. The cellular origin of elastosis in breast carcinoma remains uncertain.     

Detection of Epstein-Barr virus in breast cancers with lymphoid stroma

OBJECTIVE: the purpose of our work is to detect Epstein-Barr virus (EBV) in 2 types of breast cancer: medullary carcinoma and high grade invasive ductal carcinoma with lymphoid stroma. PATIENTS AND METHODS: we proceeded to a retrospective study of 18 medullary carcinoma and 18 high grade invasive ductal carcinoma with lymphoid stroma. The detection of the virus was carried out by immunohistochemistry with anti-LMP2 antibody and by hybridization in situ by oligonucleotides EBER1 and EBER1. LMP1 as well as hybridization in situ were positive in 5 tumors (3 medullary carcinoma and 2 high grade invasive ductal carcinoma with lymphoid stroma). RESULTS: positivity was observed in tumor cells and neither in epithelial non tumoral ones nor in lymphoid cells. DISCUSSION AND CONCLUSIONS: during numerous years, correlations between the replication of EBV and the appearance of a malignant phenotype were limited to nasopharyngeal carcinoma and to lymphoid cells. A controversy regarding the association of EBV with breast cancers has recently been reported in the literature. This cancer being very frequent, the involvement of EBV even in a small proportion of breast cancers could have important implications. Our results suggest a possible implication of EBV in these tumours but other studies are necessary.     

TADG-12 as an early marker in the development of pancreatic ductal adenocarcinoma (PDAC): Involvement of insulin containing cells

TADG-12 is a serine protease that was characterized as expressed in ovarian and gastric carcinomas. Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers and its late detection results in poor prognosis. Therefore, we decided to examine whether TADG-12 appears early in PDAC development. In normal pancreas, pale to moderate immunostaining is present in islets of Langerhans, while exocrine tissue and ducts are free from labeling. In contrast, in cancer patients, who still preserve the integrity of the exocrine and the endocrine tissues, a pronounced immunolabelling of TADG-12 was evident mainly located in the insulin containing β cells. In a more progressive stage of the disease TADG-12 was also evident in the deteriorated exocrine tissue. TADG-12 was also heavily labeled in islets of Langerhans, which were embedded in the stroma of the residual pancreatic tissue. Again, there was a considerable overlap between the labeling of insulin and TADG-12 in these islets. Close correlation between insulin and TADG-12 was also evident in islets of Langerhans surrounded by adipose cells. The TADG-12 labeled was confined to the cytoplasm and the membrane of the cells. In the progressive stage of PDAC, the cancerous ducts were clearly labeled with TADG-12 with no labeling of insulin. At high magnification the TADG-12 clearly labeled the cytoplasm and the cell wall membrane of duct cells, while the nuclei remained unstained upon incubation with antibodies to TADG-12. The present findings may assist in early detection of PDAC as well as targeting of TADG-12 in order to attenuate the rapid progression of the disease.