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Vasitis nodosa involves benign, reactive spindle-shaped nodular thickening of the ductal epithelium of vas deferens. We report the case of a 21-year-old male with a history of bilateral undescended testes and left orchidopexy. The patient presented with the complaint of a non-tender left inguinal swelling. The definitive diagnosis of vasitis nodosa was made based on clinical evaluation and imaging findings. We suggest that this rare entity should be considered as a differential diagnosis of inguinal swelling during the assessment of the male urogenital system.

Cholangiocarcinoma is a rare but lethal malignancy arising anywhere along the biliary ductal epithelium from the liver to the duodenum. The disease is classified based on anatomic location, and the mainstay of treatment is surgery. Complete resection is currently the only chance for cure despite significant advances in systemic and other nonsurgical therapies. In this chapter, we present a detailed evaluation of the anatomic classification of cholangiocarcinoma and preoperative evaluation, defining resectability, types of resections, and postoperative outcomes. Special attention is given to advances in the field and the future of surgery in the multidisciplinary management of cholangiocarcinoma.

Background: To investigate prostatic eosinophilic metaplasia (EM) in a large series of cases and their relationship with the basic prostate pathology in TURP-material: benign prostatic hyperplasia (BPH), National Institutes of Health category IV prostatitis (also called histologic prostatitis or HP), and prostatic adenocarcinoma (PCa). Aim: The relation between EM and basic prostate pathology: BPH, PCa, and HP. Materials and Methods: Around 61 consecutive TURP-specimens were reviewed for the presence of EM. The tissue sections were stained routinely with hematoxylin-eosin (HE), hematoxylin-phloxine-saffron (HPS), and periodic acid-Schiff's procedure. Simultaneously BPH, HP, and PCa were evaluated. Results: We found EM in 55.7% of TURP-specimens. EM is located more often in the ductal epithelium (58.8%) and is usually focal (73.5%) and in small groups (88.2%) of secretory luminal cells. They are associated with BPH and with a variable degree of HP in all cases. However, there is no association with PCa. Eosinophilic cytoplasmic granules in EM are better visualized with HPS. Zones induced by tissue electrocoagulation which mimic EM, are seen in the periphery of TURP-fragments. Conclusion: EM in prostate is presented by the presence of eosinophilic cytoplasmic granules in benign secretory epithelium. The study presents the first attempt to investigate EM in a large series of patients. Our results enrich the available information about the histoepidemiology of prostatic EM. Moreover, EM is more common in a focal lesion, found in small groups of ductal secretory epithelial cells while EM in TURP-specimens is associated with BPH and HP in all the cases.

Papillary lesions of the breast encompass a wide spectrum of benign and malignant lesions that arise from the ductal epithelium. These lesions comprise less than 10% of benign breast lesions, less than 2% of breast cancers, and less than 5% of all breast biopsies.1 It may be challenging to diagnose

Morphology plays an important role in the distinction of autoimmune pancreatitis (AIP) from pancreatic ductal adenocarcinoma (PDAC). However, we aimed to determine the utility of immunohistochemical tumor markers to contribute in the distinction of these entities. In surgical specimens with AIP (n = 20), PDAC (n = 20) and normal pancreas (n = 20), the expression of pVHL, maspin, IMP3, S100P and Ki67 was examined. We evaluated intralobular reactive ducts / acinoductal metaplasia (ILDs) and extralobular ducts (ELDs) in AIP, neoplastic glands in PDAC, and ductal epithelium in the normal pancreas, using a five-tiered scoring system. The Ki67 hot spot index (Ki67-HSPI) was determined manually and using automated digital imaging analysis of virtual double stains of Ki67 and CK8. Besides, sequential dual-immunohistochemical staining of maspin/pVHL, maspin/IMP3 and Ki67/maspin was performed in a subset of the specimens. Strong overexpression of IMP3, maspin, S100P and Ki67 and loss of pVHL was observed in PDAC compared to AIP and normal pancreas. In AIP however, focal and weak aberrant expression was observed with the following proportions in ILDs/ELDs: pVHL in 45 %/85 %, maspin in 30 %/70 %, IMP3 in 55 %/5%, S100P in 10 %/35 % and Ki67-HSPI >20 % in 15 %/70 %. At least two markers were aberrantly expressed in ILDs/ELDs in 45 %/60 %. The aberrant expression was more pronounced in type 2 AIP compared to type 1. In conclusion, our data indicate that pVHL, maspin, IMP3, S100P and Ki67 can be focal and weak aberrantly expressed in AIP. However, when used as a panel, these markers seem to be useful for the differentiation of AIP from PC.

Background Sialadenoma papilliferum is a benign rare condition of salivary glands showing a characteristic papillary growth of the ductal epithelium that ends up being confused with more frequent lesions of the oral cavity. Objectives: To perform a bibliometric analysis of all articles about Sialadenoma papilliferum in the oral cavity and to add a singular case report of Sialadenoma in the lower lip. Material and methods A total of 36 publications referring to Sialadenoma papilliferum in the oral cavity from the PubMed platform was reviewed. The specific data were collected, and a bibliometric analysis was performed using Microsoft Excel. The results obtained were then compared with this new case report. Results The people most affected with sialadenoma were white males at the average age of 56. The lesion was asymptomatic, usually white or red, with an average size of 1.4 cm, and the palate was by far the most affected site. The majority of the lesions were excised, and only two cases indicated recurrence. Conclusions With surgical removal, Sialadenoma papilliferum has a favorable prognosis and no further treatment is required. Due to few recorded cases of recurrence, a long follow-up period is recommended to ensure that the lesion does not redevelop. Key words:Sialadenoma papilliferum, salivary gland, oral cavity, bibliometric analysis.

Background Cysts of the salivary glands are common lesions that occur in the context of various etiologies. Although the diagnostic importance of cysts in salivary gland diseases has been well studied, molecular mechanisms that control the related pathological process remain largely unknown. IL-34 is a novel cytokine that was discovered recently as a tissue-specific ligand of colony stimulating factor-1 receptor. Since its discovery, accumulating evidence has revealed emerging roles of IL-34 in various pathological conditions and has been suggested to correlate remarkably with inflammation. In this study, we report a medical case of an inflammatory cyst within the submandibular gland, through which evaluating the possible involvement of IL-34 in salivary gland disorders. Case presentation A 37-year-old male patient suffered from a sudden swelling in the right submandibular region, started initially small and had gradually increased in size to reach 3–4 cm in 1 week, accompanied by pain and local fever. Ultrasonography and MRI imaging revealed the existence of a well-defined cystic lesion with sharp borders measuring 39.8 mm × 19.7 mm within the right submandibular gland. The cyst was removed surgically, and the diagnostic decision was determined based on histopathological observations as an inflammatory cyst in the submandibular gland. Sections were generated from different regions of the surgically resected inflammatory cyst and used to examine IL-34 expression by immunohistochemistry compared to normal salivary gland tissues. Immunohistochemical staining showed enhanced expression of IL-34 in the ductal epithelial cells and endothelial cells of blood vessels, with a tendency to be accompanied with high infiltration of immune cells, which suggests a possible involvement of IL-34 in the pathogenesis of salivary gland inflammation. Conclusions In this report, we introduce interesting findings of enhanced IL-34 expression in a case of an inflamed submandibular gland. Our findings emphasize the pathological roles of IL-34 as an inflammation amplifier and angiogenic enhancer in inflammatory conditions, such as in salivary gland disorders. Electronic supplementary material The online version of this article (10.1186/s41232-018-0069-6) contains supplementary material, which is available to authorized users.

Objective: Defective mucus production in the pancreas may be an important factor in the initiation and progression of chronic pancreatitis (CP), therefore we aimed to (i) investigate the qualitative and quantitative changes of mucus both in human CP and in an experimental pancreatitis model and (ii) to correlate the mucus phenotype with epithelial ion transport function. Design: Utilizing human tissue samples and a murine model of cerulein induced CP we measured pancreatic ductal mucus content by morphometric analysis and the relative expression of different mucins in health and disease. Pancreatic fluid secretion in CP model was measured in vivo by magnetic resonance cholangiopancreatography (MRCP) and in vitro on cultured pancreatic ducts. Time-changes of ductal secretory function were correlated to those of the mucin production. Results: We demonstrate increased mucus content in the small pancreatic ducts in CP. Secretory mucins MUC6 and MUC5B were upregulated in human, Muc6 in mouse CP. In vivo and in vitro fluid secretion was decreased in cerulein-induced CP. Analysis of time-course changes showed that impaired ductal ion transport is paralleled by increased Muc6 expression. Conclusion: Mucus accumulation in the small ducts is a combined effect of mucus hypersecretion and epithelial fluid secretion defect, which may lead to ductal obstruction. These results suggest that imbalance of mucus homeostasis may have an important role in the early-phase development of CP, which may have novel diagnostic and therapeutic implications.

Case summary Mammary fibroadenomatous hyperplasia (MFH) is a benign pathology characterised by extensive proliferation of the ductal epithelium and mammary stroma. It typically occurs in young female cats, and seems to result from hypersensitivity to progesterone. A 2-year-old entire male European Shorthair cat presented to the veterinary clinic with enlargement of several mammary glands, which had developed within the previous 10 days. There was no prior administration of progestin in the cat’s medical history. Diagnostic tests were performed to assess the basal progesterone concentration and the concentration after stimulation with gonadotropin-releasing hormone, which ruled out the presence of functional ovarian tissue. Histological examination of the testes excluded hormone-secreting testicular tumours. Histological examination of the mammary gland confirmed the diagnosis of MFH. Treatment was started with aglepristone, a selective competitor for progesterone receptors, administered subcutaneously at 15 mg/kg at days 1, 2, 8 and 15. A reduction in the size of the mammary glands was evident 6 days after the first administration, with complete remission observed after 4 weeks. Relevance and novel information To the best of our knowledge, this is the first full report of MFH in a male cat. Although the origin of the progestins responsible for MFH in this case could not be confirmed, in the light of the diagnostic tests performed and the results obtained, accidental contact with hormone-like substances seems to be the only plausible explanation for the cat’s clinical signs. Inhibitor therapy was successful.

Background. The majority of the benign and malignant lesions in the breast arise from the ductal epithelium and terminal ductlobular unit. A minimally invasive procedure called ductoscopy is able to visualize these lesions as it inspects the ductal epithelium using a small micro-endoscope. Unfortunately, it is currently challenging to obtain a tissue sample during ductoscopy and reach the most distal duct. Methods. In this study we have, therefore, developed a novel miniature (∅1.2 mm) biopsy needle that can be used during ductoscopy. This biopsy needle consists of two coaxial counter-rotating hollow blades with a distal cutout to resect lesions from the ductal wall. Three cutouts were manufactured resulting in a beveled, straight, and reverse-beveled blade. The blades were actuated using a novel mechanism containing two helical paths that allows for the counter-rotating motion of the blades at different velocities. In a proof-of-principle experiment, the performance of the biopsy needle was evaluated using a polymeric duct model and gelatin tissue phantom. Results. During the experiment, the straight and reverse-beveled blades were able to obtain a sufficiently large tissue sample for histopathological examination. Based on these promising results, a second experiment was performed in which the micro-endoscope was integrated in the needle and we were able to take a biopsy from a chicken breast. Conclusions. In a future clinical instrument, the biopsy needle will be miniaturized and optimized to allow for an efficient, safe, and effective intraductal biopsy procedure without the need for an invasive excisional biopsy procedure.

Breast diseases are combined with the pathology of other organs in 77% of cases. The primary multiplicity of tumors is now defined as the independent occurrence and development of two or more neoplasms in the body of one patient. In this case, not only different organs of different systems but also paired organs (mammary glands, lungs, etc.) can be affected. Multicentric lesions of one organ can occur as well. Combination of two tumors predominates in the structure of polyneoplasias. The cases of triple localization occur in 5–8% of cases. The risk of developing tumors in patients already having neoplasms is approximately 1.3 times higher than in those who did not previously have neoplasms. The risk of breast cancer depends on the intensity of the proliferation of the lobular and/or ductal epithelium and increases by 3–5 times at preexisting benign breast diseases, especially in combination with diseases of reproductive organs. Metastatic lesions in mammary glands can occur in cases of primary tumors of various localizations. These cases are rare and are often associated with poor prognosis.

Solid papillary carcinoma of breast is a low-grade tumour originating in the ductal epithelium. It is commonly seen in post-menopausal women and account for

We have developed an efficient simulation of breast anatomy over a range of spatial scales, covering tissue details seen in both radiology and pathology images. The simulation is based on recursive partitioning using octrees, and is performed in two stages. First, the macro- and meso-scale anatomical features are simulated: breast outline, skin, and the matrix of tissue compartments and subcompartments, outlined by Cooper's ligaments. These compartments are labeled as adipose or fibroglandular, according to the desired overall glandularity and the realistic distribution of dense tissue. Second, pathology images are generated to match selected region within the breast, by filling the region with simulated cells adipocytes, ductal epithelium and myoepithelium, lymphocytes, and fibroblasts and collagen fibers. Matched synthetic images can support discovery and virtual trials of image-based biomarkers for specific pathology findings. Our proof-of-concept is presented and further optimizations of the simulation discussed.

Gynecomastia is the most common abnormality in the male breast and has been associated with male breast cancer, but whether there is an etiological role remains unknown. In the present study we conducted an immunohistochemical investigation to further characterize gynecomastia. A total of 46 cases of gynecomastia were immunohistochemically stained on tissue microarrays for estrogen receptor (ER), progesterone receptor, HER2, androgen receptor, cytokeratins (CK5, CK14, CK7, and CK8/18), p63, E-cadherin, BRST2, cyclin D1, Bcl-2, p53, p16, p21, and Ki67. In addition, 8 cases of male ductal carcinoma in situ and normal breast tissue obtained from autopsies (n=10) and adjacent to male breast cancer (n=5) were studied. Normal ductal male breast epithelial cells were very often ER and Bcl-2 positive (69%), and progesterone receptor and androgen receptor expression was also common (39%). Gynecomastia showed a consistent 3-layered pattern: 1 myoepithelial and 2 epithelial cell layers with a distinctive immunohistochemical staining pattern. The intermediate luminal layer, consisting of vertically oriented cuboidal-to-columnar cells, is hormone receptor positive and expresses Bcl-2 and cyclin D1. The inner luminal layer is composed of smaller cells expressing CK5 and often CK14 but is usually negative for hormone receptors and Bcl-2. Male ductal carcinoma in situ was consistently ER positive and CK5/CK14 negative. In conclusion, for the first time we describe the 3-layered ductal epithelium in gynecomastia, which has a distinctive immunohistochemical profile. These results indicate that different cellular compartments exist in gynecomastia, and therefore gynecomastia does not seem to be an obligate precursor lesion of male breast cancer.

Sclerosing polycystic adenosis (SPA) was first described in 1996 by Smith et al. and was characterized by resemblance to epithelial proliferative lesions of the breast such as fibrocystic disease and sclerosing adenosis. Etiopathogenetically, it is generally believed to represent a nonneoplastic sclerosing and inflammatory process. The age range is broad (typically fourth decade), with a slight female predilection. The vast majority are parotid lesions, with very few in minor salivary glands. As of 2017, not more than 60 cases have been reported worldwide. Microscopically, it is characterized by a well-circumscribed to partially circumscribed tubulocystic proliferation of a gland within a sclerotic-fibrous stroma. Ductal epithelium showing variations such as foamy, mucous and apocrine are seen. We report a case of SPA of lower lip in a 70-year-old male.

Obstructive dysfunction of the meibomian glands (MGD) is surprisingly frequent in the general population and increases with age. Clinically, the focus is mainly on the consequences at the ocular surface in the sense of an evaporative dry eye syndrome. However, in addition, chronic obstruction of the meibomian glands also leads to degeneration of the secretory gland tissue which can result in a secondary hyposecretion even if the primary obstruction is later resolved by therapeutic approaches.Important influencing factors in the pathogenesis of obstructive MGDs and their interaction during the progression of the disease are systematically analyzed and displayed in a flow diagram. Age, hormonal disturbances and environmental influences, such as contact lenses, as well as qualitative alterations in the composition of the meibomian oil (meibum) lead to hyperkeratinization of the ductal epithelium and increased viscosity of the meibum which result, either alone or in combination, in obstruction of the duct and orifice. This leads to a lack of meibum on the lid margin and tear film with downstream hyperevaporative dry eye syndrome. At the same time, obstruction leads to a stasis of meibum inside the meibomian gland with increased pressure and resulting dilatation of the ducts and in atrophy of the acini with rarefaction of the secretory meibocytes and gland dropout. Stasis can also increase the growth of commensal bacteria, their production of oil degrading enzymes (lipases) and release of toxic mediators. These factors can, in return, act as self-enforcing feedback loops in the sense of vicious circles that aggravate the primary hyperkeratinization and compositional disturbance of meibum and can hence lead to a progressive MGD.

We previously demonstrated that Fibroblast Growth Factor 10 (FGF10) and its receptor FGFR2b play a key role in controlling the very early stages of mammary gland development during embryogenesis [Mailleux, A.A., Spencer-Dene, B., Dillon, C., Ndiaye, D., Savona-Baron, C., Itoh, N., Kato, S., Dickson, C., Thiery, J.P., and Bellusci, S. (2002). Role of FGF10/FGFR2b signaling during mammary gland development in the mouse embryo. Development 129, 53–60. Veltmaat, J. M., Relaix, F., Le, L.T., Kratochwil, K., Sala, F.G., van Veelen, W., Rice, R., Spencer-Dene, B., Mailleux, A.A., Rice, D.P., Thiery, J.P., and Bellusci, S. (2006). Gli3-mediated somitic Fgf10 expression gradients are required for the induction and patterning of mammary epithelium along the embryonic axes. Development 133, 2325–35.]. However, the role of FGFR2b signaling in postnatal mammary gland development is still elusive. We show that FGF10 is expressed at high level throughout the adipose tissue in the mammary gland of young virgin female mice whereas its main receptor FGFR2 is found mostly in the epithelium. Using a rtTA transactivator/tetracycline promoter approach allowing inducible and reversible attenuation of the FGFR2b signaling throughout the adult mouse, we are now reporting that FGFR2b signaling is also critical during postnatal mammary gland development. Ubiquitous attenuation of FGFR2b signaling in the postnatal mouse for 6 weeks starting immediately after birth is not lethal and leads to minor defects in the animal. Upon dissection of the mammary glands, a 40% reduction in size compared to the WT control is observed. Further examination shows a rudimentary mammary epithelial tree with completely absent terminal end buds (TEBs), compared to a well-branched structure observed in wild type. Transplantation of mammary gland explants into cleared fat pad of wild type mouse recipients indicates that the observed abnormal branching results from defective FGFR2b signaling in the epithelium. We also demonstrate that this rudimentary tree reforms TEBs and resumes branching upon removal of doxycycline suggesting that the regenerative capacities of the mammary epithelial progenitor cells were still functional despite long-term inactivation of the FGFR2b pathway. At the cellular level, upon FGFR2b attenuation, we show an increase in apoptosis associated with a decrease in the proliferation of the mammary luminal epithelium. We conclude that during puberty, there is a differential requirement for FGFR2b signaling in ductal vs. TEBs epithelium. FGFR2b signaling is crucial for the survival and proliferation of the mammary luminal epithelial cells, but does not affect the regenerative potential of the mammary epithelial progenitor cells.

Intraductal papillomas (IP) are benign papillary lesions caused by proliferation of mammary ductal epithelium. IP occurs in the breast tissue. Prolapse of IP from nipple can be rarely seen. IPs are generally treated with total excision. A 31-year-old female patient was admitted to our clinic because of a protruded lesion from the nipple of her right breast. On her breast examination, an 8 mm- prolapsed mass was seen on the areola of her right breast. Breast ultrasonography showed no other lesions in the breast. The patient was operated with initial diagnosis of IP. The prolapsed mass, the overlying nipple skin and related ductus were totally excised under local anesthesia. Histopathological examination of the specimen revealed intraductal papilloma without atypical dysplasia. Herein, we are presenting a rarely encountered case of IP prolapsed from the nipple of a female patient.

A number of findings suggest that cyclooxygenase-2 (COX-2) is overexpressed in breast tumours. However, there is a lack of consensus in the literature regarding the pattern of expression of this protein in invasive breast ductal carcinoma and in the adjacent non-tumour ductal epithelium. This study compares the expression of COX-2 mRNA and protein in breast ductal carcinoma relative to non-tumour breast tissue. We analysed the expression of COX-2 mRNA by quantitative PCR, and COX-2 protein by immunohistochemistry in invasive ductal carcinoma as well as in non-tumour adjacent ductal epithelium from 54 breast biopsies diagnosed as being invasive ductal carcinoma. As control, we analysed expression of COX-2 protein by immunohistochemistry in surgically-resected benign breast lesions. Our results show that COX-2 mRNA and protein are overexpressed in non-tumour ductal epithelium compared with invasive ductal carcinoma. However, the pattern of the protein expression is different in tumour and non-tumour tissue: COX-2 protein is expressed predominantly in the membrane of the non-tumour ductal epithelium (including in benign breast lesions) while, in invasive ductal carcinoma cells, it is localised in the cytoplasm. The non-tumour ductal epithelium adjacent to invasive ductal carcinoma shows a higher COX-2 expression than does the invasive ductal carcinoma. However, the different localisation of the immunohistochemically-detected protein suggests a possible post-translational regulation of the protein.

We report a rare case of a papillary cystadenoma arising from the upper lip. This tumor was not distinctly encapsulated and had proliferated replacing the ductal epithelium. Mast cells were found not only in the stroma but also in the oncocytic epithelial layer. There was a strong immunoreaction with mitochondrial antibody in the epithelial layer. Only one case (0.9%) of papillary cystadenoma has occurred among the 110 benign intraoral salivary gland tumors seen in our hospital from 1966 through September 2003.

Two related techniques of breast epithelial sampling have emerged in the past several years: ductal lavage, in which fluid-yielding nipple ducts are cannulated at their orifices and lavaged with saline while the breast is intermittently massaged; and ductoscopy, in which discharging or fluid-yielding duct orifices are dilated, intubated with a microendoscope, and the lumen directly visualized. Both of these techniques have significant potential in terms of allowing the repeated sampling of ductal epithelium over time and, as such, have generated considerable enthusiasm. However, data regarding the impact of these techniques on the detection of significant breast disease is very scant. It is important at the outset of the assessment of this new technology that breast cancer clinicians and clinical researchers think carefully about the standards of evidence that need to be met regarding the benefits of these procedures before they are widely adopted. In this review of the rationale and early results of these procedures, we attempt to define some of these evidentiary requirements.

Changes in bile ducts in cholestasis are characterized by activation of proliferation and hypertrophy of cholangiocytes and degenerative and necrobiotic changes in ductal epithelium. Long-term cholestasis led to massive necrosis of cholangiocytes. Inflammatory changes in the choledochal mucosa were most pronounced in patients with choledocholithiasis.

300 Background: Ampullary adenocarcinoma (AA) is a rare entity. AA can originate from either intestinal or pancreaticobiliary ductal epithelium, and patients are often managed as those with pancreaticobiliary carcinomas. The study objectives were the genetic profiling of AA and the identification of specific molecular profiles according to these 2 pathological types. Methods: AA patients included in the AGEO retrospective multicenter cohort who underwent surgical resection of their tumor between 1999 and 2010 were selected. Formalin-fixed, paraffin-embedded (FFPE) archival tissue blocks were collected. Next generation sequencing (NGS) using a 50 gene panel (Ion AmpliSeq Cancer panel) on tumor DNA, and immunohistochemistry (IHC) panel including CK7, CK20, MUC1, MUC2 and CDX2, on tumor sections, were performed. Results: NGS was performed on 101 tumors from 6 hospitals, with 1 technical failure. In total, the most frequent gene mutations were: KRAS (45%), TP53 (40%), APC (15%), PIK3CA (12%), SMAD4 (9%), BRAF (8%), CDKN2A (6%). No mutation was found in 21% of tumors. According to IHC, the most common histological type was intestinal (51%), followed by pancreaticobiliary type (42%) and undetermined (7%). BRAF mutation was significantly associated with intestinal type (8 vs 0, p = 0.017). According to Cosmic database, similarities of molecular profiles exist between AA with intestinal type and colorectal adenocarcinoma, and between AA with pancreaticobiliary type and pancreas adenocarcinoma, respectively. Conclusions: This study shows that AA is a heterogeneous entity and that a large proportion of AA presents a molecular profile that is more similar to that of colorectal adenocarcinoma, compared to pancreatic adenocarcinoma. This important information could be interesting to guide treatment decision in patients with this rare disease.

George F. Laidlaw first described a pancreatic abnormality now known to be the most common cause of persistent hyperinsulinemic hypoglycemia in infants in 1938 (1, 2). The term he coined, nesidioblastosis, is derived from the Greek words for “islets” (nesidia) and “germ” (blastos) (3). It accurately describes the characteristic feature of nesidioblastosis, islet cells differentiating and budding from ductal epithelium. In adults, hyperinsulinemic hypoglycemia is rarely caused by nesidioblastosis and is usually caused by insulinoma or exogenous insulin treatment (4, 5). The first case series of adult nesidioblastosis was reported by Harness et al in 1981 (6). Since this case series of six patients, there have been only sporadic literature reports of adult nesidioblastosis, documenting fewer than 20 cases of adult nesidioblastosis over the past 15 years (3, 7-10). This paper presents an adult patient with hyperinsulinemic hypoglycemia due to nesidioblastosis and provides a guide to the diagnosis and treatment of this rare disorder in the adult population.

The localization of IgA, IgG, and IgM was investigated immunohistochemically in the mucosal surface of the main excretory duct of the human submandibular gland in order to verify the possible antimicrobial properties of this duct. Only secretory IgA-immunoreactivity was recognized in the epithelial cells of the duct. An intense immunoreactivity was observed in the cytoplasm of some cells and at the luminal surface of most of the cells. Clusters of IgA-positive immuno-competent cells were also recognizable in the subepithelial layers. No reactivity for IgG and IgM was noticed. The results suggest that the ductal epithelium may actively be involved in the release of secretory IgA, which could play a prominent role in the local defense mechanism of the duct.

Triple-negative breast cancers (TNBCs) are a heterogeneous set of tumors defined by an absence of actionable therapeutic targets (ER, PR, and HER-2). Microdissected normal ductal epithelium from healthy volunteers represents a novel comparator to reveal insights into TNBC heterogeneity and to inform drug development. Using RNA-sequencing data from our institution and The Cancer Genome Atlas (TCGA) we compared the transcriptomes of 94 TNBCs, 20 microdissected normal breast tissues from healthy volunteers from the Susan G. Komen for the Cure Tissue Bank, and 10 histologically normal tissues adjacent to tumor. Pathway analysis comparing TNBCs to optimized normal controls of microdissected normal epithelium versus classic controls composed of adjacent normal tissue revealed distinct molecular signatures. Differential gene expression of TNBC compared with normal comparators demonstrated important findings for TNBC-specific clinical trials testing targeted agents; lack of over-expression for negative studies and over-expression in studies with drug activity. Next, by comparing each individual TNBC to the set of microdissected normals, we demonstrate that TNBC heterogeneity is attributable to transcriptional chaos, is associated with non-silent DNA mutational load, and explains transcriptional heterogeneity in addition to known molecular subtypes. Finally, chaos analysis identified 146 core genes dysregulated in >90% of TNBCs revealing an over-expressed central network. In conclusion, use of microdissected normal ductal epithelium from healthy volunteers enables an optimized approach for studying TNBC and uncovers biological heterogeneity mediated by transcriptional chaos.

Superficial papillary adenomatosis of the nipple is a benign tumor of the ductal epithelium that clinically resembles Paget's disease. Histologically, the tumor is characterized by proliferating ductal structures lined by a double layer of columnar epithelium. Keratin cysts and apical intraluminal projections are commonly found. Since this entity's original description as "florid papillomatosis" in 1954, 174 cases have been reported in the English language literature. We review these cases and report a classic example.

Dry eye disease is a prevalent eye disorder that in particular affects the elderly population. One of the major causes of dry eye, meibomian gland dysfunction (MGD), shows increased prevalence with aging. MGD is caused by hyperkeratinization of the ductal epithelium of meibomian gland and reduced quantity and/or quality of meibum, the holocrine product that stabilizes and prevents the evaporation of the tear film. Of note, retinoids which are used in current anti-aging cosmetics may promote the development of MGD and dry eye disease. In this review, we will discuss the possible mechanisms of age-related MGD.

Purpose Obstructive Meibomian gland dysfunction (MGD) is a widespread alteration and represents a main reason for evaporative dry eye syndrome. Hyper-keratinisation of the ductal epithelium in response to various pathological stimuli appears as a typical underlying reason. Methods Own morphological data together with findings from the literature on Meibomian gland anatomy, physiology and pathology are discussed and used to propose factors and their interactions involved in the pathology of obstructive MGD. Results A large body of literature indicates that obstruction of the Meibomian gland is an important and widespread contributor to the pathology in MGD. Several findings indicate that keratinisation of the ductal system and orifice is the primary factor in obstruction of the gland. Histological and immunohistological data indicate that the whole ductal epithelium of the normal Meibomian gland shows signs of incipient stages of keratinisation, derived from its embryological ancestry. Hence, the gland preserves a commitment to full keratinisation if a proposed developmental block is removed due to various factors. Keratinisation leads to obstructive stasis of secretum inside the gland and to dilatation of the ductal system as well as to atrophy of the secretory acini. This results not only in decreased availability of Meibomian oil on the lid margin and tear film but also to secondary hypo-secretion. Increase of commensal bacteria and their products may have a certain role in this process although a real infection does not usually occur. Conclusion Events in obstructive MGD which share hyper-keratinisation as a starting point, interact via different pathways that may form vicious circles and eventually lead to evaporative dry eye and gland atrophy.

The majority of breast diseases result from lesions of the ductal epithelium. Mammary ductoscopy allows for visualization of intraductal abnormalities, and ductoscopic lavage provides thousands of cells for analysis. We reviewed our experience of 89 cases of patients with pathologic nipple discharge (PND) undergoing ductoscopy-directed duct excision and collection of ductal washings. Patients undergoing ductoscopy-directed duct excision with ductal washings had an 88% abnormal pathology rate. Most abnormalities were benign (71% papillomas), but the atypia rate for this group was 62%. The combination of visualization and pathologic analysis of washings provided the highest predictive value for the diagnosis of papilloma. Cellular yields for this technique were excellent with most specimens yielding >5,000 epithelial cells per high powered field and with evaluable ductal cells in 82% of specimens. Mammary ductoscopy offers the advantage of a high lesion localization rates with intraoperative guidance. The most accurate tool was the combination of ductal washings and ductoscopic visualization, but preoperative use of these techniques is not helpful in most cases. Greater than 90% of patients with PND are found to have a lesion on pathologic examination when using this technique for directed duct excision. Of interest, ductal washings obtained from symptomatic patients with benign diseases are often atypical.

Four 4-month-old ostriches exhibiting poor growth were submitted for necropsy. Gross findings included marked emaciation and pancreatic atrophy. Histological examination revealed pancreatic cryptosporidiosis with large numbers of Crypto-sporidium sp. present in the ductal epithelium causing necrosis and lymphoplasma-cytic inflammation. The gross and histological findings in these birds and the transmission electron microscopic features of the parasites are described.

Morphological changes occur in breast ductal epithelium during menstrual cycle. Electrical contact with ductal epithelium was established using a nipple electrode in 51 pre-menopausal women scheduled for breast biopsy. Epithelial impedance spectroscopy (EIS) measurements were obtained over a frequency range of 0.1 Hz-60 kHz. Seven of the 51 patients tested had ductal hyperplasia and demonstrated a high transepithelial ductal resistance (Re), 225 ± 59 kΩ, that did not appear to vary during menstrual cycle. However, significant differences were observed in patients with non-proliferative disease tested in week 1 and 4 of cycle (Wk 1, 4), (n=23) compared to those tested in week 2 and 3 (Wk 2, 3), (n=21). Re of the ducts were higher in Wk 2, 3 with values of 281 ± 59 kΩ compared with an Re of 114 ± 19 kΩ in patients tested in Wk 1, 4 (p < 0.05). The capacitance of the ductal system appeared non-significantly higher in Wk 1, 4 with a value of 8.40 ± 7.70 μF, compared with 0.28 ± 0.03 μF in patients tested in Wk 2, 3, (p = 0.097). This study demonstrates that menstrual cycle affects the electrical signature of the ductal epithelium in patients with benign breast disease, and can be measured non-invasively.

Bioimpedance approaches to breast cancer diagnosis generally use surface electrodes, which pass a signal through the breast to identify changes in impedance. We have developed a different technique that non-invasively passes an imperceptible electrical current through the nipple to the terminal ducts in the breast to identify changes in impedance due to hyperplasia and depolarization across the ductal epithelium where breast cancer develops. Electrical contact with ductal epithelium was established non-invasively, using a nipple electrode in 200 women scheduled for breast biopsy. Transepithelial potential (TEP) and transepithelial impedance were obtained over a frequency range (0.1 Hz - 60 kHz) and processed using a frequency response analyzer/sine-wave correlation technique. In patients with malignant (n=70) or proliferative lesions (n=58) the TEP was depolarized by 10 ± 2 mV (mean ± SEM, (p 10mm), (n=30), (p < 0.001).

Most breast cancers originate in the ductal epithelium with normal cells progressing to atypia and finally to carcinoma. Ductoscopy enables one to visualize and sample the ductal epithelium and therefore identify early changes cytologically. This report describes our experience with mammary ductoscopy as a tool for evaluation of nipple discharge at Beth Israel Medical Center.A prospective review of all patients who have undergone ductoscopy for evaluation of persistent nipple discharge was performed. The Acueity ductoscopy system with .9-mm scope and a video monitor with x60 magnification were used. Brush biopsy samples and lavage fluid were obtained from some patients and were sent for cytologic analysis. A subset of patients underwent ductoscopically guided duct excision.Ninety-three patients underwent ductoscopic evaluation of 110 ducts. Of these, 67 patients had abnormal findings and therefore underwent ductoscopically guided duct excision. The remaining 26 patients (28%) had normal ductoscopic examinations. The depth at which intraductal abnormalities were visualized was from 3 to 8 cm with an average of 4.4 cm for cancer cases and from 1 to 10 cm with an average of 4.5 cm for papillomas. Forty-two patients were diagnosed with papilloma/papillomatosis, six patients were diagnosed with atypical papilloma/atypical ductal hyperplasia/atypical lobular hyperplasia, and six patients were diagnosed with cancer. Of the six patients diagnosed with cancer, 67% had normal breast imaging, and other than nipple discharge, 67% had normal breast examinations.Mammary ductoscopy is a useful tool in the evaluation of patients with nipple discharge. Although the most common cause of nipple discharge is an intraductal papilloma, nipple discharge can be the presenting symptom for cancer. Our experience revealed a papilloma rate of 45% (42 of 93), cancer rate of 6.5% (6 of 93), and an atypia rate of 6.5% (6 of 93) among the patients with nipple discharge. Mammary ductoscopy allows for accurate visualization, analysis, and excision of intraductal abnormalities. Many deeper intraductal abnormalities could be missed by blind surgical excision.

Intraductal papillomas are rare benign tumors, most commonly encountered in minor salivary glands and rarely in major salivary glands. They are cystic, solitary neoplasm that arise from ductal epithelium and produce painless swelling. We report a case of intraductal papilloma of the parotid gland in a child.

Invasive ductal carcinoma (IDC) of the pancreas arises in the ductal epithelium and extends into the pancreatic tissue via stromal invasion. Carcinoma in situ (CIS) is believed to be a precursor les

Objective To investigate the histologic and molecular changes in the ipsilateral and contralateral epididymides in response to unilateral testicular torsion followed by detorsion. Design Controlled experimental study using rats. Setting Seoul National University College of Medicine, Seoul, Korea. Animal(s) Thirty-five, 8-week-old Sprague-Dawley male rats: six experimental groups and a sham-operated control group. Intervention(s) Testes of male rats were subjected to torsion for 10 minutes. At 0, 1, 4, 8, 24 hours and 1 week after detorsion, ipsilateral and contralateral epididymides were harvested. Microscopic examination and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) staining was performed. The percentage of apoptotic ducts in the epididymis was determined by counting 100 duct cross-sections of the head and the tail of the epididymis of each specimen. Main outcome measure(s) Morphologic change, including in situ apoptosis, of the ductal epithelium was evaluated. Result(s) There was no evidence of morphologic or apoptotic changes in the 0- or 1-hour detorsion groups. However, enlargement of the interstitial fibrous tissue was found 8 and 24 hours after detorsion and marked degeneration of ductal epithelium was observed at 1week in both the ipsilateral and contralateral epididymides. Apoptosis was first observed at 4 hours after detorsion, and the percentage of apoptotic ducts was significantly increased at 8 hours, peaked at 24 hours, and slightly decreased at 1 week in both the ipsilateral and contralateral epididymides. Conclusion(s) Both morphologic changes and intracellular molecular alterations occur not only in the ipsilateral but also in the contralateral epididymis following unilateral testicular torsion/detorsion.

Salivary duct carcinoma (SDC) is a rare, extremely aggressive malignancy arising in the ductal epithelium of the salivary glands. Radiologic investigations of and reports on minor salivary gland SDC are very rare. We present 3 cases of SDC of the palate with the attendant radiologic features and clinicopathologic findings. We also review English-language reports with radiologic findings regarding SDC and minor salivary gland SDC. MR imaging findings such as low signal intensity on T2-weighted images, infiltrative margins, and poor enhancement, in particular, should be recognized as indicators of high-grade malignancy such as SDC and, as such, should be considered when making a differential diagnosis.

A squamous cell carcinoma of the buccal mucosa probably arising in the minor salivary glands was reported.About 1 month before presentation, a 65-year-old female noticed a tumor on the right buccal mucosa. It was superior to the right parotid papilla, hemospheric in form, measured 1.4 cm in diameter, and was mobile with an elastic firm consistency. The overlying mucosa was generally smooth. No abnormalities were detected by clinical examination. The tumor was removed along with the surrounding tissue. Histological examination revealed a well differentiated squamous cell carcinoma. Nodular carcinoma cell nests appeared immediately beneath the mucosa. The rests proliferated by replacing the minor salivary glands. Thickening (proliferation) of ductal epithelium was noted in the neighboring salivary glands.Neither recurrence nor metastasis have occurred as of 4 years and 3 months after surgery.

Salivary gland papillomas are rare tumours arising from ductal epithelium. Intraduct papillomas are the most rare of all duct papillomas. Only four intraduct papillomas have been described in a review of nearly 3100 epithelial salivary tumours. Intraduct papillomas are located almost exclusively in the excretory ducts of the minor salivary glands. However, also the major salivary glands may be affected. Microscopically, the tumour consists of fibrovascular papillae covered by a columnar or cuboidal epithelium. The authors describe an intraduct papilloma of the palate in a 74-year-old woman. The excision of the lesion was curative.

Oncocytic metaplasia of palatine gland ducts was demonstrated by light and electron microscopy in seven out of 54 dogs. Oncocytes were recognized as distinct swollen epithelial cells with bright eosinophilic cytoplasm, small dark nuclei and scattered microvilli at the luminal surface. Their cytoplasm contained numerous tightly packed mitochondria, which varied in size and shape. Some oncocytes formed nodular hyperplastic foci that were easily recognized by low-power light microscopy. Oncocytic metaplasia appears to be a common incidental finding in palatine ductal epithelium of older dogs.

Background: Optical coherence tomography (OCT) is a high-resolution imaging technique that produces cross-sectional images in vivo. This is a report of the first use of OCT to acquire images of the biliary tree during ERCP. Methods: A 2.6-mm diameter OCT catheter delivered through the accessory channel of a duodenoscope was used to acquire images of the intrahepatic and extrahepatic bile ducts in 5 patients. Histology-correlated OCT images of 5 cadaveric livers, each imaged at 3 sites, were used to guide interpretation of the in vivo images. Results: Biliary ductal epithelium and subepithelial structures, including peribiliary glands, vasculature, and hepatic parenchyma, were visualized in vivo. The papillary architecture of cholangiocarcinoma was identified by OCT. There were no OCT-related complications. Conclusions: High-resolution OCT imaging of the biliary tree is feasible and may provide useful diagnostic information during ERCP.

Transforming growth factor e (TGFe) was demonstrated immunohistochemically in the bovine mammary gland, mainly in the glandular and ductal epithelium. In the teat, its expression was largely limited to the skin keratinocytes, ductal epithelium and ductal glands. It is suggested that this growth factor plays a role in lactation.

Three patients with congenital mechanical intestinal obstruction and features of syndromic paucity of the interlobular bile ducts (SPILBD) are presented. Two of them have siblings with syndromic paucity of the interlobular bile ducts. Two patients had jejunoileal atresia, while the other had a meconium plug with intestinal perforation. All subjects underwent surgery for intestinal obstruction within the first 24 h of life. Progressive disappearance of the bile ductules was observed in one case. We believe that an insult such as vascular insufficiency to both bile ductal epithelium and the small intestine may be the cause of this congenital disorder.

Purpose: This investigation was undertaken to determine the damage to the testes and epididymides following torsion and detorsion of the testes. Materials and Methods: The right testes of 8-week-old male rats (n=30) were subjected to torsion for 10 min. At 0, 1, 4, 8, and 24 hours, and 1 week after the repair of a torsion, the ipsilateral and contralateral testes and epididymides were harvested. The mean number of spermatids per tubule, the mean seminiferous tubular diameter (MSTD), and the germinal epithelial cell thickness (GECT) were used to evaluate changes to the testes. The histologic changes to the epididymal ductal epithelium were also evaluated. Results: The mean number of spermatids per tubule, GECT, and MSTD were significantly decreased in the 24-hour ipsilateral detorsion group, but minimal changes to ipsilateral testes were observed in the 1-week detorsion group. There was no evidence of histologic changes to the testes in any of the contralateral detorsion groups. The interstitial fibroblast proliferation and hemorrhage of the ipsilateral epididymis were found in the 4-hour detorsion group and increased in the 8-hour detorsion group. Interstitial fibroblast proliferation was prominent in the ipsilateral epididymis of the 24-hour detorsion group, but was only occasionally observed in the contralateral epididymides. Shortening of the tubular epithelial cell height and tubule dilatation were observed in the ipsilateral and contralateral epididymis 1 week after detorsion. Conclusions: Torsion/detorsion damage was found earlier and at a higher intensity in the epididymides than in the testes. This finding may be due to the protection afforded by the blood-testis barrier. (Korean J Urol 2008; 49:945-952) 󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏