Availability of CD10 immunohistochemistry as a marker of breast myoepithelial cells on paraffin sections.

CD10, also called common acute lymphoblastic leukemia antigen (CALLA), was recently found to be expressed in nonhematopoietic tissues. Although CD10 was also identified in human breast myoepithelial cells, its availability of immunohistochemistry on paraffin sections has not been examined so far. In the present study, we demonstrated CD10 immunohistochemically on paraffin sections of both normal and pathological breast tissues, comparing its staining patterns to those of smooth muscle actin (SMA), which is now commonly used to highlight myoepithelium. CD10 was consistently positive in normal breast myoepithelial cells. CD10 also clearly highlighted myoepithelial cells in intraductal papilloma, adenosis, ductal hyperplasia, fibroadenoma, and phyllodes tumor as well as SMA did. In atypical ductal hyperplasia and ductal carcinoma in situ, continuous, discontinuous, and totally negative stainings of both CD10 and SMA were noted, depending on foci of neoplastic cell nests. However, both stainings clearly demonstrated myoepithelial cells of cancerized acini, being useful in differentiating lobular cancerization from microinvasion. Because SMA was also positive in normal vessels and spindle-shaped stromal cells, CD10, which was negative in vessels, was useful in differentiating myoepithelial cells from thin vascular wall in intracystic lesions with delicate papillae. Although background staining of spindle-shaped stromal cells was also noted in CD10, the positive cell number was less, and the signal was weaker than that of SMA. The absence of myoepithelial cells in invasive ductal carcinomas was more clearly highlighted by CD10 than SMA. We concluded that CD10 could be another useful marker of breast myoepithelial cells on paraffin sections. Combination of CD10 and SMA will provide more sophisticated information about presence or absence of myoepithelial cells in confusing breast lesions.     

Enzyme histochemistry is useful to assess viability of tumor tissue after microwave coagulation therapy (MCT): metastatic adenocarcinoma treated by lateral segmentectomy after MCT

We report on a case of metastatic adenocarcinoma of liver that was removed and examined histochemically after microwave coagulation therapy (MCT). The patient was a 65-year-old woman who had a metastatic tumor in the liver (S3) after high anterior resection due to a rectal adenocarcinoma and received MCT against the tumor. One month after MCT, multiple metastatic tumors were detected by abdominal computed tomography (CT) scan. As it was difficult to control them by MCT alone, we performed lateral segmentectomy. To assess the effects of microwave ablation on cellular viability of metastatic tumor, we used enzyme histochemistry for acid phosphatase (AcP), which is positive in macrophages infiltrating in the tumor. In a part of the ablated area of resected liver, there was remaining neoplastic tissue of which the morphology was maintained in H&E staining. This was found to be microwave-fixed non-viable tissue because no enzyme activity of AcP was detected in the infiltrating macrophages. This case report suggests that enzyme histochemistry was useful to assess the effect of MCT, enabling us to distinguish fixed cells from viable cells.     

Mitotic activity and apoptosis in endocervical glandular lesions.

To evaluate the significance of mitotic activity and apoptosis in the differential diagnosis of endocervical glandular lesions, we examined the frequency of mitoses and apoptosis in 89 endocervical glandular lesions from 78 patients, which consisted of benign reactive changes (7 cases), lobular or diffuse laminar endocervical glandular hyperplasia (4), microglandular hyperplasia (3), tunnel clusters (7), nabothian cysts (2), mesonephric remnants (3), tubal metaplasia (3), endocervical glandular dysplasias (including atypical tubal metaplasia) (EGD) (7), adenocarcinoma in situ (AIS) (31), microinvasive adenocarcinoma (7), frankly invasive adenocarcinoma (12), and minimal deviation adenocarcinoma (3). Mitotic index (MI; mitotic figures per 1000 cells) was significantly higher in AIS, microinvasive adenocarcinoma, and frankly invasive adenocarcinoma than any other lesions examined. Microinvasive adenocarcinoma showed the highest MI. Apoptosis was detected consistently and frequently in AIS, microinvasive adenocarcinoma, and frankly invasive adenocarcinoma. AIS showed the highest apoptotic index (AI; apoptoses per 1000 cells). Frequent apoptotic bodies and mitotic figures are a common feature of endocervical glandular malignancies (except for minimal deviation adenocarcinoma) and are an important feature that can facilitate their differentiation from benign and borderline lesions. High MI in microinvasive adenocarcinoma might aid the distinction of microinvasive adenocarcinoma from AIS. Although both MI and AI of EGD were between those of benign reactive changes and of AIS, MI and AI alone are not sufficient to differentiate EGD from benign reactive changes. MI and AI are not helpful in the differential diagnosis between minimal deviation adenocarcinoma and its benign mimics.     

Endogenous ghrelin in pancreatic islets restricts insulin release by attenuating Ca2+ signaling in beta-cells: implication in the glycemic control in rodents

Ghrelin, isolated from the human and rat stomach, is the endogenous ligand for the growth hormone (GH) secretagogue receptor, which is expressed in a variety of tissues, including the pancreatic islets. It has been shown that low plasma ghrelin levels correlates with elevated fasting insulin levels and type 2 diabetes. Here we show a physiological role of endogenous ghrelin in the regulation of insulin release and blood glucose in rodents. Acylated ghrelin, the active form of the peptide, was detected in the pancreatic islets. Counteraction of endogenous ghrelin by intraperitoneal injection of specific GH secretagogue receptor antagonists markedly lowered fasting glucose concentrations, attenuated plasma glucose elevation, and enhanced insulin responses during the glucose tolerance test (GTT). Conversely, intraperitoneal exogenous ghrelin GH-independently elevated fasting glucose concentrations, enhanced plasma glucose elevation, and attenuated insulin responses during GTT. Neither GH secretagogue receptor antagonist nor ghrelin affected the profiles of the insulin tolerance test. In isolated islets, GH secretagogue receptor blockade and antiserum against acylated ghrelin markedly enhanced glucose-induced increases in insulin release and intracellular Ca2+ concentration ([Ca2+]i), whereas ghrelin at a relatively high concentration (10 nmol/l) suppressed insulin release. In single beta-cells, ghrelin attenuated glucose-induced first-phase and oscillatory [Ca2+]i increases via the GH secretagogue receptor and in a pertussis toxin-sensitive manner. Ghrelin also increased tetraethylammonium-sensitive delayed outward K+ currents in single beta-cells. These findings reveal that endogenous ghrelin in islets acts on beta-cells to restrict glucose-induced insulin release at least partly via attenuation of Ca2+ signaling, and that this insulinostatic action may be implicated in the upward control of blood glucose. This function of ghrelin, together with inducing GH release and feeding, suggests that ghrelin underlies the integrative regulation of energy homeostasis.     

A new method of complete peripheral margin assessment in breast conservative surgery using an adjustable polygonal prism mould

Conventional margin evaluation for breast conservative surgery is usually based on the sections taken perpendicular to the inked margins and has difficulty in completeness. We have developed a new method using an adjustable mould during fixation so that the three-dimensional specimen is fixed in the shape of polygonal prism. The new method enables us to assess peripheral margins completely by examining the inner surfaces of the marginal slices cut parallel to the flat peripheral margins of the specimen. DESIGN: We have applied the new method to 59 invasive carcinomas and 10 noninvasive carcinomas of the breast, which were judged to be negative for residual tumor by conventional inked margin on the section cut through the center of the tumor. RESULTS: The new method detected 13(22.0%) and 3(30.0%) cases with positive margins in 59 invasive carcinomas and 10 noninvasive carcinomas of the breast, respectively. Nine of 13(69.2%) positive margins in invasive carcinomas were due to the intraductal components of the carcinomas. CONCLUSION: The polygon method is superior to the conventional inked margin method in sensitivity. Furthermore, it covered all the peripheral margins and pinpointed the positive sites.     

Topographical, morphological and immunohistochemical characteristics of carcinoma in situ of the breast involving sclerosing adenosis. Two distinct topographical patterns and histological types of carcinoma in situ

Moritani S, Ichihara S, Hasegawa M, Endo T, Oiwa M, Shiraiwa M, Nishida C, Morita T, Sato Y, Hayashi T, Kato A, Aoyama H & Yoshikawa K
(2011) Histopathology  58 , 835–846
Topographical, morphological and immunohistochemical characteristics of carcinoma in situ of the breast involving sclerosing adenosis. Two distinct topographical patterns and histological types of carcinoma in situ Aim: To examine the histopathological features of 24 surgically resected carcinoma in situ (CIS) involving sclerosing adenosis (SA), with special reference to the topographical relationship between CIS and SA. Methods and results: In 13 (54%) lesions, CIS was entirely surrounded by SA (type A) and in 11 (46%), CIS involved SA at least focally but was not confined to the SA area (type B). The mean size of CIS in type B (30.45 mm) was significantly larger than in type A (18.00 mm). The mean size of SA in type A (39.46 mm) was significantly larger than in type B (19.54 mm). Most type A CIS were non‐high‐grade, and the oestrogen receptor (ER)(+)/progesterone receptor (PgR)(+)/HER2(?) immunophenotype predominated. Most type B CIS were high‐grade and six (54%) were ER(?)/PgR(?). Most type A were bcl‐2(+)/p53(?) in both SA and CIS areas, but two (18%) apocrine ductal CIS of type B were bcl‐2(?)/p53(+) in both SA and CIS areas. Expression of ER and cyclin D1 in SA was not different from that of SA unassociated with cancer. Conclusions: Most CIS involving SA arises within SA and high‐grade DCIS tends to grow beyond SA. Occasional CIS may arise outside SA and secondarily involve SA.     

Real-time endobronchial ultrasound-guided transbronchial needle aspiration is useful for diagnosing sarcoidosis

BACKGROUND AND OBJECTIVE: Several studies of real-time endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) have reported a sensitivity of approximately 90% in the diagnosis of mediastinal and hilar malignancies. However, few studies have addressed its role in the diagnosis of sarcoidosis. The aim of the present study was to assess the utility of EBUS-TBNA in confirming a pathological diagnosis of sarcoidosis. METHODS: Fifteen consecutive patients with suspected sarcoidosis and mediastinal and/or hilar lymphadenopathy were investigated prospectively. EBUS-TBNA with an echo-bronchoscope and a dedicated echogenic 22-gauge needle was carried out in patients under conscious sedation, followed by conventional TBNA of the same lesion using a 19-gauge needle. RESULTS: EBUS-TBNA and/or TBNA demonstrated non-caseating epithelioid cell granulomas in 14 of 15 patients (93%). All 14 patients with a pathological diagnosis of sarcoidosis were considered to have sarcoidosis based on subsequent clinical assessments. The single patient with a negative EBUS-TBNA and TBNA had a malignant melanoma diagnosed following surgical biopsy. EBUS-TBNA confirmed a diagnosis of sarcoidosis in 13 of the 14 patients (93%) by identifying non-caseating epithelioid cell granulomas in 18 of 23 lymph nodes (78%) sampled. When two needle aspirates of one or two lymph nodes were carried out, the percentage positive pathological diagnosis for sarcoidosis for (i) EBUS-TBNA; (ii) TBNA; and (iii) the combination of EBUS-TBNA and TBNA were 93% (13 of 14 patients), 93% (13 of 14 patients) and 100% (14 of 14 patients), respectively. There were no complications associated with the procedures. CONCLUSION: EBUS-TBNA is less invasive and acceptably sensitive as a method for obtaining pathological confirmation of sarcoidosis.