The time-course of changes in renal tissue composition during lysine vasopressin infusion in the rat

Summary The corticomedullary osmolal gradient, largely dissipated by sustained water-diuresis, was progressively repleted by continuous i.v. ADH infusion (lysine-vasopressin, 15 mU/min/100 g body weight) in conscious rats for up to 41/2 hr.A marked increase in sodium content was essentially complete by 1/2 hr in the papillary tip; smaller, but more progressive increases occurred in the papillary base and inner medulla. Increases in medullary urea content occurred mainly in the first 21/2 hr, especially in the papillary tip. A progressive decrease in water content of all medullary segments was preceded by a significant papillary tip increase at 1/2 hr.Papillary tip-urine osmotic equilibration was slowly achieved after about 21/2 hr. The small, but significant, tip-urinary urea concentration difference of water diuresis was more rapidly replaced by a substantial difference in the reverse direction.It is concluded that the changes can be explained, adequately, by ADH-induced modifications in water and urea permeabilities of distal nephron segments and, possibly, by changes in inner medullary blood flow; that the evidence of direct ADH stimulation of sodium transport is inconclusive; and that there was no evidence of active urea transport.     

The time course of changes in renal tissue composition during water diuresis in the rat

1. The time course and extent of changes in the composition of renal tissue slices in water diuresis were determined by sacrificing groups of rats before and during the intravenous infusion of dextrose (2.5 g/100 ml.) in amounts sufficient to administer over 2 hr, and subsequently to maintain for up to 7(1/2) hr, a positive fluid load of 4% body weight.2. The corticomedullary osmolal gradient characteristic of the nondiuretic rats was progressively dissipated until, at 7(1/2) hr, only papillary tip concentrations were higher than those of other segments.3. The changes in individual constituents followed different time courses: (i) an increase in water content in all segments, particularly the papilla, was almost complete by 1 hr, preceding the maximal increases in urine flow; (ii) a marked decrease in papillary and medullary urea content in the first hour was followed by a slower, progressive decrease leading to an almost complete dissipation of the urea gradient by 7(1/2) hr; (iii) small, non-significant decreases in sodium content occurred in all segments in the first hr, followed by a further small, progressive decrease in papillary sodium content; (iv) changes in ammonium and potassium concentrations were mainly related to those in water content, since the contents of these solutes showed only small changes.4. By 2 hr, differences in the rates of decline of osmolal and urea concentrations in urine and papilla led to urinary concentrations significantly lower than papillary values. The steep papilla-urine urea concentration difference became smaller, but remained significant even at 7(1/2) hr.5. The findings are discussed in terms of changes in countercurrent mechanisms, particularly as influenced by anti-diuretic hormone.6. The development of papilla/urine urea concentration ratio greater than unity is also considered in terms of passive transport with changes in membrane permeability.     

The time course of changes in renal tissue composition during mannitol diuresis in the rat

1. The time course and extent of changes in the composition of renal tissue slices in osmotic diuresis were determined by sacrificing groups of rats before and during the intravenous infusion of mannitol (15 g/100 ml.) for up to 7½ hr.

2. Very rapid changes in tissue water and solute contents occurred within 15 min, preceding the times of maximal diuresis, with little subsequent change even up to 7½ hr.

3. The main changes were:

(a) an increase in water content in all slices, particularly the papilla; (b) a very profound decrease in papillary and medullary urea content in the first 15 min, with a small, but significant, further decrease, subsequently; (c) a small, but significant, rapid decrease in papillary sodium, and small non-significant increases in the outer medulla and cortex. Subsequent changes in any segment were small and non-significant; (d) apart from small changes in the first 15 min ammonium and potassium contents remained fairly constant.

4. The rates of change in papillary and urinary urea concentrations were similar, so that after 30 min, any differences between tip and urinary concentrations were small and non-significant.

5. The findings are discussed in terms of factors influencing counter-current mechanisms. It is concluded that altered medullary blood flow is mainly responsible for the rapid changes in medullary composition.

6. The relation between papillary and urinary urea concentrations is explicable in terms of passive handling, with equilibration across a freely permeable collecting duct membrane.

     

Effects of 0·9% saline infusion on urinary and renal tissue composition in the hydropaenic, normal and hydrated conscious rat

1. Changes in water and solute outputs of hydropaenic, normal and hydrated conscious rats were determined during intravenous infusion (0.2 ml./min) of isotonic (0.9%) saline for 4 hr; renal tissue composition was determined before, and after 1 or 2 hr, infusion.2. In normal and hydrated rats increased excretion of water and sodium was such that urinary output matched intravenous input from about 2 hr. In hydropaenic rats, the diuretic and natriuretic response was much reduced; a retention of infused saline, equivalent to 15% body weight, occurred over 4 hr.3. A considerable increase in urea output and clearance, and a smaller increase in potassium and ammonium outputs, occurred in all groups.4. The corticomedullary osmolal gradients characteristic of non-diuretic rats were largely dissipated during saline infusion: by 1 hr in normal and hydrated rats, and by 2 hr in the hydropaenic group.5. These changes were ascribable mainly to an increase in tissue water content in all segments, particularly in the hydropaenic group; and to a profound decrease in urea content in all groups.6. Changes in tissue sodium content were smaller, and differed between segments and between the differently hydrated groups. A decrease in papillary content occurred in hydropaenic and normal groups and an increase in cortical and outer medullary content occurred in all groups.7. After 2 hr saline infusion, incomplete papillary-urinary osmotic equilibration was evident in all groups.8. These changes in medullary osmolality and in papillary-urinary osmotic equilibration preceded the maximal diuresis, and must contribute to the diuresis induced by saline infusion, as in water and osmotic diureses.     

A sequential study of the bovine tuberculin reaction.

The sequential histopathological and immunocytochemical changes that characterize the tuberculin reaction were studied in 13 cattle experimentally sensitized to Mycobacterium bovis, and 14 cattle naturally infected with M. bovis. There were two distinct, temporally related patterns of morphological change that were similar for both groups of cattle. The first phase, between 6 hr and 24 hr after the intradermal injection of purified protein derivative (PPD), was characterized by a perivascular aggregation of WC1+ gamma delta T cells and neutrophils and the presence of leucocytoclastic vasculitis within the papillary dermis. The second phase of the reaction was characterized by increased numbers of infiltrating BoCD4+ cells, BoCD8+ cells and macrophages, as well as an increase in expression of the interleukin-2 (IL-2) receptor and the ACT2 antigen. Macrophages were the most numerous infiltrating leucocytes between 24 hr and 72 hr after the intradermal injection of PPD. At 72 hr, the reaction was characterized by intense perivascular cuffing with BoCD4+ cells, BoCD8+ cells and macrophages; gamma delta T cells and neutrophils were a minor component of the reaction and leucocytoclastic vasculitis was no longer observed. No B cells were detected in the dermis throughout the period of study. The increase in skin thickness was primarily because of inflammatory oedema that was contained within the area by a meshwork of fibrin deposited around the collagen bundles of the reticular dermis.     

Influence of prehydration on the changes in renal tissue composition induced by water diuresis in the rat

1. The composition of renal tissue was determined in rats before and immediately after intravenous infusion of dextrose (2.5 g/100 ml.) in amounts sufficient to administer a positive fluid load of 4% body weight over 2 hr. The rats were classified into three groups, according to the preinfusion urine osmolality: hydropaenia, normal and moderately diuretic (over 2400, 800-1500 and below 800 mu-osmoles/g H(2)O, respectively).2. In non-infused rats, the steepness of the corticomedullary osmolal gradient varied, due to differences in both water and solute (sodium and urea) contents, and was related to urinary osmolality. Whereas differences in medullary and papillary solute contents occurred between all three groups, papillary water content was significantly higher only in the moderately diuretic animals.3. Dextrose infusion caused the induction of water diuresis, the lowest urinary osmolalities being produced in the previously moderately diuretic animals.4. Dextrose infusion caused a considerable reduction in the steepness of the corticomedullary osmolal gradient in all rats, particularly in the previously hydropaenic animals, due to changes in both solute (sodium and urea) and water contents. Whereas reductions in medullary and papillary solute contents occurred in all three groups, there was no further increase in papillary water content from the already high values seen in the noninfused diuretic animals.5. Thus, dextrose infusion largely abolished any previous differences in tissue water content, whereas significant, though small, differences in osmolal (particularly urea) content persisted.6. These data are discussed in terms of changes and differences in endogenous antidiuretic hormone (A.D.H.) release.7. Changes in the magnitude and direction of the urinary-papillary urea concentration difference are discussed in terms of passive transport, with probable A.D.H.-induced changes in nephron urea permeability.     

Inhibitors of prostaglandin synthesis inhibit growth of human cytomegalovirus and reactivation of latent virus in a productively and latently infected human cell line

Indomethacin and tetracaine, inhibitors of prostaglandin synthesis, inhibited production of infectious human cytomegalovirus (HCMV) in a human thyroid papillary carcinoma cell line (TPC-1) by 99.9% when added to cultures at the concentration of 2 x 10(-4) M during the first 24 hr after infection. Although immediate early virus proteins were synthesized at similar molar ratios in mock- and compound-treated cultures, induction of HCMV-specific DNA polymerase (one of the early virus proteins) was inhibited by treatment with these compounds, suggesting that the early stages of the virus growth cycle are most likely to be under the control of indomethacin or tetracaine action. We have previously developed an in vitro HCMV latency model system in TPC-1 cultures. This system was used to study the effect of these compounds on reactivation of the latent virus. When TPC-1 cultures preheated for 48 hr at 40.5 degrees were infected with HCMV and incubated at 40.5 degrees, the cultures could be maintained for 30 days without detection of infectious virus. The latent HCMV was reactivated within 10 days by reducing the incubation temperature from 40.5 to 37 degrees. However, when the latently infected cultures were treated with indomethacin or tetracaine immediately after being shifted to 37 degrees, reactivation of the latent virus was not observed.     

Cellular swirls in fine needle aspirates of papillary thyroid carcinoma: a new diagnostic criterion.

No single cytologic feature is specifically diagnostic for papillary thyroid carcinoma. We report herein the presence of swirl-like cellular aggregates in fine needle aspirates of papillary thyroid carcinoma but not in other thyroid entities. Cellular swirls are defined as concentrically organized aggregates of tumor cells in which many of the most peripherally situated cells have ovoid rather than round nuclei that are oriented perpendicular to the radius of the swirl. One hundred Papanicolaou- and/or Diff-Quik-stained FNAs of the thyroid diagnosed as papillary carcinoma, including seven fine needle aspirates of cervical lymph nodes showing metastatic papillary carcinoma, with or without cell blocks, were reviewed for the presence of cellular swirls. An additional 100 thyroid FNAs, similarly stained and prepared, diagnosed as nodular goiter, Hashimoto's thyroiditis and follicular neoplasm were also reviewed for the presence of cellular swirls. Cellular swirls were easily observed at screening magnification and confirmed at high magnification. Seventeen of 100 FNAs (17%) of papillary carcinoma contained cellular swirls. No cases diagnosed as nodular goiter, Hashimoto's thyroiditis or follicular neoplasm contained these structures. Thirteen cases with swirls had histologic follow-up. These comprised seven papillary carcinomas with classical histopathology, two designated 'differentiated papillary carcinoma,' two with follicular variant histopathology; one with a minor component of follicular variant histopathology; one papillary carcinoma metastatic to a cervical lymph node with classic histopathology. Swirls occurred in cases with relatively little pleomorphism, or in well-differentiated regions of papillary carcinoma that also displayed less well-differentiated components. Cellular swirls are a finding that is highly specific to papillary thyroid carcinoma. They are easily seen at screening magnification. Their presence in a FNA specimen may be helpful in cases where classic criteria for papillary thyroid carcinoma are scarce, particularly in well-differentiated papillary thyroid carcinoma. While the size and scope of this study are insufficient to conclude that cellular swirls alone are diagnostic of papillary thyroid carcinoma in the absence of other criteria, we believe these structures should be added to the list of diagnostic criteria.     

Hashimoto's thyroiditis shares features with early papillary thyroid carcinoma

Neoplastic transformation is a multistep process that results in a continuous spectrum from the normal (physiological) state to a fully established neoplasm. The gold standard for diagnosis of papillary thyroid carcinoma is conventional histology, the essential element being the characteristic nuclear features, regardless of whether papillary structures are present or not. However, other criteria are being used increasingly in the diagnosis of neoplasms, including immunohistochemical staining and molecular profile. The RET/PTC gene rearrangement is highly specific for papillary thyroid carcinoma and is associated with the characteristic nuclear features seen in papillary thyroid carcinoma. There is an overlap in the morphological features, immunohistochemical staining pattern, and most importantly, molecular profile between papillary thyroid carcinoma and Hashimoto's thyroiditis. Although considered a 'benign' condition, Hashimoto's thyroiditis almost always harbours a genetic rearrangement that is strongly associated with and is highly specific for papillary thyroid carcinoma. Submicroscopic foci of papillary thyroid carcinoma must be present in Hashimoto's thyroiditis, although the clinical behaviour is still benign. Further studies are required to predict which foci will progress to papillary thyroid carcinoma.     

Hürthle cell and mitochondrion-rich papillary carcinomas of the thyroid gland: an ultrastructural and immunocytochemical study

Of 52 consecutive papillary carcinomas of the thyroid, the following cases were included in this study: one Hürthle cell papillary carcinoma, one papillary carcinoma with foci of Hürthle cells, and 10 cases of papillary carcinoma with abundant mitochondria (volumetric density of mitochondria greater than or equal to 20%). All cases were studied by light microscopy, transmission electron microscopy (TEM), scanning electron microscopy (SEM), and immunocytochemistry. Our results showed that papillary carcinomas mainly or exclusively composed of Hürthle cells are very rare; that Hürthle cell papillary carcinomas of the thyroid share the biologic characteristics and blend insidiously with the so-called mitochondrion-rich papillary carcinomas; that TEM and SEM can provide useful evidence for achieving the differential diagnosis between Hürthle cell and so-called mitochondrion-rich papillary carcinomas; and that immunocytochemical studies are useless in the aforementioned differential diagnosis.     

Impact of the 1998 World Health Organization/International Society of Urological Pathology classification system for urothelial neoplasms of the kidney.

The classification of urothelial neoplasms of the kidney traditionally has been similar to that of urinary bladder tumors. Several years ago, the classification of papillary urothelial neoplasms was revised. The current study focuses on the application of the 1998 World Health Organization (WHO)/International Society of Urological Pathology classification system to 102 renal pelvic urothelial neoplasms and compares it to the 1973 WHO classification scheme. In this study, all tumors were classified as urothelial carcinomas, and the majority (85%) were papillary. Most patients with papillary tumors presented with 'superficial' disease (< or = pT1). With the 1998 system, most papillary carcinomas were high grade, and were more often invasive as compared to low-grade tumors. Only 34% were low-grade papillary tumors and, of these, most (93%) were noninvasive. With the 1973 system, most papillary tumors were grade 2 or 3, with invasion more common in grade 3 tumors. By 1973 criteria, grade 2 tumors were a heterogeneous group; with 1998 criteria, nearly one-half were high grade and the other half low grade. The grade of papillary urothelial carcinomas with both the 1973 and 1998 grading methods was associated with stage (P=0.001). Our study reveals that papillomas and papillary urothelial neoplasms of low malignant potential are uncommon tumors in the kidney. Renal pelvic papillary urothelial neoplasms are most often carcinomas and are more commonly high grade than low grade. Although both the 1973 and 1998 systems showed a significant association with tumor stage, grade 2 papillary carcinomas are a heterogeneous group by 1973 criteria. The 1998 system provides useful information in that it more clearly defines a papillary tumor's grade and selects for a group of tumors, namely low-grade papillary urothelial carcinomas, for which a low likelihood of invasion can be predicted.     

Intraductal papillary mucinous neoplasm

Intraductal papillary mucinous neoplasm (IPMN) is a grossly visible (≥1 cm), mucin-producing neoplasm that arises in the main pancreatic duct and/or its branches. Patients with intraductal papillary mucinous neoplasm can present with symptoms caused by obstruction of the pancreatic duct system, or they can be asymptomatic. There are 3 clinical subtypes of intraductal papillary mucinous neoplasm: main duct, branch duct, and mixed. Five histologic types of intraductal papillary mucinous neoplasm are recognized: gastric foveolar type, intestinal type, pancreatobiliary type, intraductal oncocytic papillary neoplasm, and intraductal tubulopapillary neoplasm. Noninvasive intraductal papillary mucinous neoplasms are classified into 3 grades based on the degree of cytoarchitectural atypia: low-, intermediate-, and high-grade dysplasia. The most important prognosticator, however, is the presence or absence of an associated invasive carcinoma. Some main duct-intraductal papillary mucinous neoplasms progress into invasive carcinoma, mainly tubular adenocarcinoma (conventional pancreatic ductal adenocarcinoma) and colloid carcinoma. Branch duct-intraductal papillary mucinous neoplasms have a low risk for malignant transformation. Preoperative prediction of the malignant potential of an intraductal papillary mucinous neoplasm is of growing importance because pancreatic surgery has its complications, and many small intraductal papillary mucinous neoplasms, especially branch duct-intraductal papillary mucinous neoplasms, have an extremely low risk of progressing to an invasive cancer. Although most clinical decision making relies on imaging, a better understanding of the molecular genetics of intraductal papillary mucinous neoplasm could help identify molecular markers of high-risk lesions. When surgery is performed, intraoperative frozen section assessment of the pancreatic resection margin can guide the extent of resection. Intraductal papillary mucinous neoplasms are often multifocal, and surgically resected patients should be followed for metachronous disease.     

Papillary lesions of the breast

Papillary lesions include benign and malignant lesions. As this array of papillary lesions cannot be differentiated by clinical and imaging means, the diagnosis relies on pathologic examination. Intraductal papillomas are benign, and often complicated by superimposed epithelial metaplasia or hyperplasia. When they are involved by atypical duct hyperplasia, the prevailing practice is to upgrade the diagnosis to ductal carcinoma in situ when the extent of involvement is ≥3 mm. Intraductal papillary carcinomas has low grade malignant epithelial changes, retaining an outer myoepithelial layer but lost the myoepithelial cells within the lesion around fibrovascular cores. Encapsulated papillary carcinomas and solid papillary carcinomas have distinctive morphology, but both are characterized by frequent loss of myoepithelial cells surrounding the lesion, although the current classification still consider these to be in situ lesions. Invasion is used for irregular groups, tongues and nests of tumor cells extending into the stroma beyond the rounded boundary. Immunohistochemistry is useful in differentiating papillary lesions, with positivity of myoepithelial markers, high molecular weight cytokeratins and heterogeneous staining of ER denoting benignity and vice versa. Core needle biopsy is frequently used in diagnosing papillary lesions: both under- and over-diagnoses may occur, the former being more frequent. Genetically papillary carcinomas are grouped mostly into luminal cancers, further attesting to the generally low grade nature of all subtypes of papillary carcinomas.     

Hereditary and Sporadic Papillary Renal Carcinomas with c-met Mutations Share a Distinct Morphological Phenotype

Germline mutations of c-met oncogene at 7q31 have been detected in patients with hereditary papillary renal cell carcinoma. In addition, c-met mutations were shown to play a role in 13% of patients with papillary renal cell carcinoma and no family history of renal tumors. The histopathology of papillary renal cell carcinoma with c-met mutations has not been previously described. We analyzed the histopathology of 103 bilateral archival papillary renal cell carcinomas and 4 metastases in 29 patients from 6 hereditary papillary renal cell carcinoma families with germline c-met mutations and 6 papillary renal cell carcinomas with c-met mutations from 5 patients with no family history of renal tumors. Twenty-five sporadic renal tumors with prominent papillary architecture and without somatic c-met mutations were evaluated for comparison. All papillary renal cell carcinomas with c-met mutations were 75 to 100% papillary/tubulopapillary in architecture and showed chromophil basophilic, papillary renal cell carcinoma type 1 histology. Fuhrman nuclear grade 1-2 was seen in tumors from 23 patients, and nuclear grade 3 was observed focally in 8 patients. Seventeen patients had multiple papillary adenomas and microscopic papillary lesions in the surrounding renal parenchyma. Clear cells with intracytoplasmic lipid and glycogen were focally present in tumors of 94% papillary renal cell carcinoma patients. Clear cells of papillary renal cell carcinoma had small basophilic nuclei, and clear cell areas lacked a fine vascular network characteristic of conventional (clear) cell renal cell carcinoma. We conclude that papillary renal cell carcinoma patients with c-met mutations develop multiple, bilateral, papillary macroscopic and microscopic renal lesions. Renal tumors with c-met genotype show a distinctive papillary renal cell carcinoma type 1 phenotype and are genetically and histologically different from renal tumors seen in other hereditary renal syndromes and most sporadic renal tumors with papillary architecture. Although all hereditary and sporadic papillary renal cell carcinomas with c-met mutations share papillary renal cell carcinoma type 1 histology, not all type 1 sporadic papillary renal cell carcinomas harbor c-met mutations.     

Differentiated papillary kidney tumors. Differentiation between metanephric adenoma and papillary adenoma

Metanephric adenoma of the kidney is a well described tumor entity. The differential diagnosis between papillary adenoma or papillary carcinoma type 1 and metanephric adenoma of the kidney can be challenging in single cases. We report two cases of metanephric adenomas and compare their immunophenotype with a papillary adenoma. The analysis of these metanephric adenomas and a review of the literature shows that CD-57 positivity and lack of EMA expression are helpful in distinguishing metanephric adenoma from papillary adenoma and papillary carcinoma. Glomeruloid structures, Psammoma bodies, necrosis or expression of cytokeratin 7 and vimentin are common features in metanephric adenoma and papillary adenoma or papillary carcinoma. The knowledge of the immunohistochemical constellation is important, because metanephric adenoma can be very large and often have some necrosis.     

Differential diagnosis of renal tumors with papillary architecture

Papillary renal cell carcinoma is the second most common malignant renal epithelial tumor and constitutes approximately 15% of renal cell tumors. However, papillary architecture is neither unique to papillary renal cell carcinoma, nor do all papillary renal cell carcinomas show exclusive papillary histology. Many of the nonpapillary renal cell carcinomas with papillary architecture have been recognized only recently. Distinction of these from papillary renal cell carcinoma is essential, as biologic behavior and potential therapeutic options are distinct in many such tumors. Close attention to the cytologic and growth pattern characteristics will allow us to arrive at the proper diagnosis in most cases, although sometimes immunohistochemistry and rarely genetic evaluation may be needed.     

Prognostic significance of atypical papillary urothelial hyperplasia

Typical papillary hyperplasia, a recently recognized precursor lesion to low-grade papillary urothelial neoplasms, consists of undulating folds of cytologically benign urothelium. Well-developed, branching fibrovascular cores of a papillary neoplasm are not evident. We have noted lesions with the architectural pattern of papillary hyperplasia; however, the overlying urothelium demonstrated varying degrees of cytologic atypia. We identified 15 cases of atypical papillary hyperplasia (13 males, 2 females, age 55 to 92) with overlying urothelium showing cytologic atypia. Of these cases, 8 (53%) were received in consultation. Of the 15 cases, 8 exhibited overlying flat carcinoma in situ (CIS), 4 had overlying dysplasia, and 3 were transitional between papillary hyperplasia with atypia and the earliest lesions of papillary neoplasia. Of these cases, 5 patients had multiple specimens with atypical papillary hyperplasia (range, 2 to 8) over time. Concurrent to the diagnosis of atypical papillary hyperplasia, there were 25 different urothelial lesions: CIS (n = 11), papilloma (n = 1), papillary neoplasm of low malignant potential with CIS (n = 1), high-grade papillary urothelial carcinoma (n = 10; 3 with CIS), small-cell carcinoma (n = 1), and infiltrating urothelial carcinoma (n = 1). Of 11 patients with known prior history, 2 had 12 prior urothelial neoplasms (9 low-grade papillary neoplasms, 2 papillary urothelial neoplasms of low malignant potential, and 1 high-grade papillary cancer). Of 10 patients with atypical papillary hyperplasia and a minimum of 1 year of follow-up, 9 had 19 recurrences: CIS (n = 4), papilloma (n = 1), papillary neoplasm of low malignant potential (n = 1), infiltrating urothelial carcinoma (n = 3; 1 with CIS), and high-grade papillary urothelial carcinoma (n = 10; 5 with invasion and 2 with CIS). Whether the papillary hyperplasia had overlying CIS or dysplasia did not affect the correlation with urothelial neoplasms. Immunohistochemical analysis of p53 and Ki-67 expression in 8 cases demonstrated overexpression of p53 (n = 2; 1 with overlying dysplasia and 1 with overlying CIS), and Ki-67 (n = 5; 2 with overlying dysplasia and 3 with overlying CIS). Taken together, these results suggest that atypical papillary hyperplasia is most frequently associated with CIS and high-grade papillary cancer. In some cases, CIS or dysplasia may evolve into atypical papillary hyperplasia, with further progression to high-grade papillary cancer. This process may be analogous to papillary hyperplasia without cytologic atypia progressing to low-grade papillary urothelial neoplasms.     

Papillary lesions of the breast – review and practical issues

Papillary lesions of the breast represent a heterogeneous group of neoplasm featuring fibrovascular cores covered by epithelial cells with or without intervening myoepithelial cells. According to the World Health Organization classification of breast tumors, papillary lesions of the breast are further classified into intraductal papilloma (including intraductal papilloma with atypical ductal hyperplasia /ductal carcinoma in situ), papillary ductal carcinoma in situ, encapsulated papillary carcinoma, solid papillary carcinoma (in situ and invasive) and invasive papillary carcinoma. The overlapping morphological features and immunohistochemical profiles make accurate diagnosis of breast papillary lesion a challenge for pathologists. In this review, the morphological and relevant immunohistochemical features of papillary lesions are discussed, with further emphasis on some commonly encountered practical diagnostic issues. A simple diagnostic algorithm will be established. The relevant molecular characteristics will be discussed as well.     

Pseudomyxoma peritonei (mucinous carcinoma peritonei) preceded by intraductal papillary neoplasm of the bile duct

Pseudomyxoma peritonei (mucinous carcinoma peritonei) is a rare clinical disease. Although most cases derive from appendiceal mucinous tumors, a few are associated with pancreatic intraductal papillary mucinous neoplasms. Intraductal papillary neoplasms of the bile duct share many similarities with pancreatic intraductal papillary mucinous neoplasms and are thought to be their biliary counterparts. We report a case of low-grade intraductal papillary neoplasm of the bile duct who developed pseudomyxoma peritonei 6 years after surgical treatment of the primary biliary tumor. To the best of our knowledge, this is the first case of pseudomyxoma peritonei associated with intraductal papillary neoplasm of the bile duct. The tumor recurrence in our case may be due to tumor spillage at the time of the first surgery, since there is no recurrent biliary tumor in the preserved liver lobe. Prevention of spillage of epithelial cell-containing mucin during surgical operations is important in treating intraductal papillary neoplasms of the bile duct.     

Cell architecture in the papillary layer of rat incisor enamel organ at the stage of enamel maturation

Shape and arrangement of cells and extent of intercellular spaces were studied in sections of enamel organ cut in three planes: at right angles to the axis of the incisor tooth, at right angles to the axis of the ameloblasts, and parallel to the axes of the incisor and ameloblasts. The cells in contact with the base of the ameloblasts make up the proximal part of the papillary layer. They have a polygonal cross section close to the ameloblasts and point several sheet-like cell processes towards the blood vessels which invaginate in the papillary layer. Intercellular spaces of constant width pervade the proximal part and provide a direct and straight communication between blood vessels and ameloblasts. The cells of the ridges make up the distal part of the papillary layer, and are flattened in the direction of the ridges. Intercellular spaces in the ridges are narrower than in the proximal part and visible with the light microscope only during a fraction of the enamel maturation period. No distinct cell layers are visible within the papillary layer during enamel maturation. All cells in the papillary layer may be in contact with the basement membrane investing the enamel organ. The structure of the papillary layer changes with the different phases of enamel maturation. Functional aspects of the papillary layer are briefly discussed.