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Part 1 book “Histology for pathologists” has contents: Serous membranes, small intestine, vermi orm appendix, anal canal, gallbladder and extrahepatic biliary system, the lymph nodes, bone marrow, urinary bladder, ureter and renal pelvis, penis and distal urethra,… and other contents.
21 Serous Membranes Da rryl Ca rte r ■ La w r e n c e Tr u e ■ Ch ris to p h e r N Otis ANATOMY 585 REACTIVE MESOTHELIUM 595 Reactive versus Neoplastic Mesothelium 596 Reactive Mesothelium versus Carcinoma 596 Endosalpingiosis and Endometriosis 597 Fibrous Pleurisy 598 Multilocular Peritoneal Inclusion Cyst 598 FUNCTIONAL ANATOMY 586 MESOTHELIAL CELLS 588 Morphology 588 Histochemistry 589 Immunohistochemistry 591 Ultrastructure 593 SUBMESOTHELIAL LAYER 593 Histochemistry 593 Immunohistochemistry 595 Interactions o Mesothelial and Submesothelial Cells REFERENCES 599 595 ANATOMY The mesothelium lines the pleural, pericardial, and peritoneal cavities Mesothelial cells on the serous surfaces appear as a simple or cuboidal epithelium, although they are of mesodermal origin They are supported by a brous submesothelial layer, which becomes continuous with the outer layer of invested viscera The serous membranes show functional differentiation according to their derivation from visceral or parietal mesoderm Because of space limitations, description of the gross anatomy of the mesothelium must be somewhat truncated, but some areas have functional differentiation that is re ected by their histologic features The pleura is a continuous membrane that covers the chest wall and the lungs The visceral pleura coats the entire pulmonary surface, including the major and minor ssures that divide the lungs into lobes, whereas the parietal pleura extends over the ribs, sternum, and supporting structures and is re ected over the mediastinal structures on both right and left Posteriorly in the mediastinum, the two layers of parietal pleura are separated by a thin band of brovascular connective tissue Superiorly, the cervical pleura is re ected into the retroclavicular area over the apex of the lung and is coated by a thickened layer of brous tissue and skeletal muscle; inferiorly, the diaphragmatic pleura represents its caudal extent Anteriorly, the pleura is re ected over part of the pericardium The posterior visceral pleura becomes continuous with the diaphragmatic pleura over the pulmonary ligament The heart and great vessels lie in the pericardium, which is lined by a continuous layer of mesothelium The visceral (epicardial) side is connected to the myocardium, and the parietal (pericardial) layer rests on a dense brous tissue layer containing branches of the internal mammary and musculophrenic vessels, descending aorta, and branches of the vagus, phrenic, and sympathetic nerves The thoracic surface of the pericardium is coated with parietal pleura The peritoneum is a nearly continuous membrane lining the potential space between the intra-abdominal viscera and the abdominal wall In females, it is normally interrupted by the lumina of the fallopian tubes Anatomically, it is more complex than either the pleura or the pericardium The parietal layer covers the abdominal wall, diaphragm, anterior surfaces of the retroperitoneal viscera, and the pelvis The visceral peritoneum invests the intestines and other intra-abdominal viscera The elongated structures in which the parietal and visceral layers come together are the mesentery, which contains blood vessels, lymphatics, lymph nodes, and nerves 585 586 S E C TIO N VI: Th o x a n d Se ro u s Me m b n e s The greater omentum is a double sheet with four layers of mesothelium between which there are numerous blood vessels and adipose tissue, which may be abundant; lymphatics and lymph nodes are less prominent than in the mesentery The peritoneal cavity is grossly divided into the greater sac over the intestines, the retrogastric lesser sac, the right and left retrocolic areas, and the pelvis Several outpouchings of peritoneum are often seen in pathology laboratories Inguinal hernia sacs are pouches of parietal peritoneum, often invested with brous tissue and occasionally with skeletal muscle, which have been pushed through the abdominal musculature into the inguinal canal Umbilical or ventral hernias are also outpouchings of peritoneum, but the specimens received by pathologists after surgery for their repair are usually preperitoneal broadipose tissue pushed ahead of the parietal peritoneum rather than mesothelium itself The scrotum acquires a lining of parietal mesothelium, the processus vaginalis, into which the testes descend during the seventh month of gestation A mesothelial layer forms the surface of the tunica vaginalis Distention of this mesothelial sac on the tunica vaginalis results in a hydrocele—communicating with the peritoneal cavity when congenital but noncommunicating in acquired hydroceles The sac of an inguinal hernia communicates with the peritoneal cavity and not with the mesothelium-lined space of the scrotum Both hernia and hydrocele sacs are capable of a wide range of reactive changes FUNCTIONALANATOMY The functional anatomy of the pleura was described by Sahn (1) and Pistolesi et al (2) The pleura is a continuous membrane surrounding a space that normally contains approximately 10 mL of clear colorless uid The surface is lined by a single layer of mesothelial cells anchored to a basement membrane that lies on layers of collagen and elastic tissues containing vascular and lymphatic vessels The lining mesothelial cells are 16 to 40 µ m in diameter, have rounded nuclei, usually displaying a nucleolus, and a relatively large amount of cytoplasm Although the visceral and parietal pleurae are opposing parts of the same continuous membrane, there are major functional differences between them The human visceral pleura is thick relative to that seen in some other mammals (3) and is similar to that of horses, cattle, sheep, and pigs (4) It has an arterial blood supply from the bronchial arteries, with a venous return that passes rst into the pulmonary veins and then into the left atrium except for certain hilar regions that are drained by bronchial veins into the right atrium The lymphatics that pass through the visceral pleura are the super cial layer of pulmonary lymphatics with extensive connections to the peribronchial, perivascular, and interlobular lymphatic spaces FIGURE 21.1 Visceral pleura The mesothelial cells on the sur ace are f attened and, when viewed in pro le, so thin as to be barely evident On the posterior sur ace o the le t lower lobe, the dense submesothelial layer is composed o collagen and elastin, and extends into adjacent pulmonary interstitium and around pulmonary vessels and lymphoid tissue (5) Blood and lymphatic vessels are invested by two layers of collagen and elastic bers; an external elastic lamina supports the mesothelial cells and an internal layer invests the vessels and becomes continuous with the pulmonary interstitium (Figures 21.1, 21.2) Histologic identi cation of integrity of the visceral pleural elastin is considered clinically important in determining pleural invasion by primary lung cancer, which is signi cant for staging (6) However, the elastin layer of the visceral pleura is also interrupted in non-neoplastic conditions of the lung that extend to the pleura In sheep, and probably in humans, the thickness of the external layer increases in both the craniocaudal and ventrodorsal directions, perhaps because of postural reasons (7) The visceral pleura is innervated by branches of the vagus nerves and sympathetic nerve trunks The parietal pleura is anatomically, histologically, and functionally different Although the single layer of mesothelial cells that lie on the surface of the parietal pleura are cytologically similar to those that form the continuous membrane over the visceral pleura, they are interrupted by stomata which range in size from to 12 µ m in diameter Li (8) described the stomata on the human diaphragmatic pleura as usually penetrating deep through connective tissue with apparent communication between the pleural cavity and the underlying lymphatic lacunae In some areas, stomata were covered with great microvilli (longer and CH AP TER : Se ro u s Me m b n e s FIGURE 21.2 Visceral pleura Capillaries are prominent, the lymphatics are dilated, deeply placed and entirely invested by the submesothelial layer with a denser network of laments) on the surfaces of the surrounding mesothelial cells The underlying lymphatics drain directly into intercostal lymphatics and then into the mediastinum, where they are particularly dense along the retrocardiac surface (9–16) Fluid and particulate matter extravasated from the lung are collected in these lymphatics and passed into the mediastinum, where the mesothelium covers collections of macrophages called Kampmeier foci (17) Boutin et al (18) showed concentration of asbestos bers in these areas, which are also termed “black spots” when there is concentration of carbon in individuals who have inhaled coal dust Miserocchi et al (19) discussed asbestos ber accumulation in “black spots” corresponding to the stomata The arterial and venous blood supply to the parietal pleura is from the intercostal vessels The thickness of the broelastic layer investing the parietal pleural lymphatics is relatively constant and considerably less than that of most of the visceral pleura, suggesting that it serves as a membrane across which uid may diffuse The parietal pleura is innervated by branches of the intercostal nerves, which are responsible for the pain associated with pleurisy Wassilev et al (20) described stomata on the peritoneum of the abdominal wall, omentum, mesentery, ovaries and pelvis as well as on the underside of the diaphragm They found variation in the structure of the stomata according to location The parietal stomata were clustered, oval in shape and delimited by attened mesothelial cells, whereas the hepatic stomata were deeper gaps in adjacent cuboidal 587 mesothelial cells and were covered or occluded by the microvilli on the surface of mesothelial cells Li and Yu (21) found that the diaphragmatic stomata were approximately 10 µ m2 in size, among cuboidal but not attened mesothelial cells, and opened into submesothelial connective tissue in which there was a rich plexus of lymphatics, which they suggested carried away peritoneal uid and particles The serous membranes serve as a selective barrier for uid and cells A small volume of uid is required for capillary action to facilitate adherence of visceral and parietal pleurae as the lungs and chest wall expand and contract Elements of the serous membranes regulate uid interchange to keep this uid at a minimal level to prevent compromise of the lung volumes Control appears to be at the capillary level because uid is freely diffusible through visceral mesothelium and is collected in parietal lymphatics via stomata in the parietal mesothelium The bushy, elongated microvilli, which are the diagnostic hallmark of mesothelial cells, are sometimes enlarged where associated with stomata Another level of control results from the relatively low protein content (1.0 to 1.5 g/dL) of pleural uid The point of protein regulation is unknown, although there is speculation that it occurs at the level of mesothelial microvilli (21) In the thoracic cavity, the direction of ow appears to be via diffusion from capillaries of both visceral and parietal pleurae, with resorption primarily through parietal pleural capillaries Turnover is estimated at 0.7 mL/hr (21) (Figure 21.3) Small molecules (less than nm in diameter) diffuse through the intercellular spaces and junctions between mesothelial cells Loss of control results in serous effusions such as those seen in congestive heart failure FIGURE 21.3 Model o the dynamics o pleural f uid ormation A transudate rom capillaries in visceral and parietal pleurae is partly reabsorbed by those capillaries and the rest di uses into the pleural space, where it is resorbed via stomata into parietal pleural lymphatics 588 S E C TIO N VI: Th o x a n d Se ro u s Me m b n e s Larger molecules, up to 50 nm in diameter, are transferred across the mesothelium by pinocytotic uptake and transcellular transport Larger structures, such as cells in bloody effusions, are transported via the stomata and “crevices.” Loss of control of these mechanisms results in accumulation of exudative pleural uid Mesothelial cells express the secretory component of IgA, which is otherwise limited to surfaces with direct environmental contact (22,23) The glycoprotein-rich pleural uid acts as a lubricant to minimize friction between visceral and parietal pleurae The site of synthesis and mechanisms of control of the carbohydrate-rich fractions of the pleural uid are unknown The submesothelial connective tissue distributes mechanical forces from the pleura uniformly throughout the lungs Such a redistribution of forces is not required of the abdominal serosa Both mesothelial cells and broblasts contribute to collagen synthesis MESOTHELIALCELLS FIGURE 21.5 At higher magni cation, a sheet o relatively normal mesothelial cells with abundant, clear cytoplasm and crisply de ned cell borders The centrally placed nuclei are small and have a homogenous chromatin Morphology Normal mesothelial cells are rarely seen in histologic sections but may be evident in cytologic preparations of peritoneal washes taken during a laparotomy (Figure 21.4) When thus visualized, they have abundant clear cytoplasm with crisply de ned cell borders, small and centrally placed nuclei with a homogeneous chromatin pattern, and usually without a nucleolus (Figure 21.5) In a variety of reactive processes, the mesothelial cells undergo markedly proliferative and hyperplastic changes A relatively abundant cytoplasm is maintained, but the cell borders are less sharply de ned The nuclei are larger, both absolutely and relatively, the chromatin pattern is more hyperchromatic, and nucleoli are often present and prominent (Figures 21.6–21.9) FIGURE 21.6 This detached ragment o reactive mesothelium shows an intact mesothelial layer with cells in two phases o the reactive process shown in Figures 21.7, 21.8 FIGURE 21.4 In this peritoneal wash specimen, a sheet o normal mesothelial cells has been detached FIGURE 21.7 The reactive mesothelial cells rom the le t side o Figure 21.6 have abundant cytoplasm, and the nuclei are larger with a more vesicular chromatin pattern Nucleoli are present but not prominent CH AP TER : Se ro u s Me m b n e s FIGURE 21.8 The more reactive mesothelial cells rom the right side o Figure 21.6 have less cytoplasm, larger nuclei with a more vesicular chromatin pattern, and more prominent nucleoli As the hyperplastic changes in the reactive mesothelial cells progress, cell groups become smaller, and individual cells predominate When clustered, reactive mesothelial cells present an irregular outside border The nucleus, and especially the nucleolus, may enlarge dramatically, but the nuclei are similar in size, shape, and pattern from cell to cell Normal mitotic gures may be seen The cytoplasm may become multivacuolated as the cells degenerate and imbibe uid (Figures 21.10–21.18) 589 FIGURE 21.10 This individual reactive mesothelial cell has a limited amount o cytoplasm and a relatively large nucleus with a nucleolus The cell border is highly irregular and uzzy, consistent with the presence o the numerous elongated microvilli, which are evident on electron microscopy (see Figure 21.24) The cytoplasm is divided into an outer less dense layer and an inner denser layer, which, ultrastructurally, corresponds to the presence o intermediate laments with the characteristics o keratin (see Figure 21.25) Mesothelial positivity for histochemical stains that detect negative groups, such as the positively charged dye Alcian blue, is evidence of their content of acid mucoproteins That the intensity of staining reactions for acid mucosub- stances is diminished by preincubating the tissue sections in hyaluronidase is evidence that at least some of the terminal hexose groups of the mucosubstances are either hyaluronic acid or chondroitin sulfate Furthermore, the fact that histochemical mucin is decreased, but not abolished, by incubating cells in neuraminidase before histochemical staining is evidence that some of the terminal carbohydrate groups are sialated (24) MacDougall et al (25) have documented that neoplastic mesothelial cells may stain with mucicarmine Negativity for the periodic acid-Schiff (PAS) reaction after sialase digestion is evidence that mesothelial cells lack signi cant quantities of neutral mucoproteins FIGURE 21.9 In this sheet o reactive mesothelial cells, the cytoplasm is smaller and the nuclei are relatively larger and have a more irregular chromatin pattern FIGURE 21.11 Mesothelial reaction is requently associated with inf ammatory cells These reactive mesothelial cells, which are several times the size o either neutrophils or lymphocytes, are joined as a pair Histochemistry 590 S E C TIO N VI: Th o x a n d Se ro u s Me m b n e s FIGURE 21.12 These reactive mesothelial cells are loosely joined together The uppermost cell has a vacuole in the cytoplasm, which could be either a vesicle or an intracytoplasmic lumen FIGURE 21.15 Normal mitotic gures may be seen in the proli erating cells o reactive mesothelium FIGURE 21.13 When reactive mesothelial cells are in groups, an irregular or “knobby” outside border is ormed, whereas acini orm a smooth outer border Note the “ uzzy” border on the mesothelial cell FIGURE 21.16 The nucleoli o reactive mesothelial cells may be prominent FIGURE 21.14 Occasionally, very reactive mesothelial cells may show cellular interactions similar to those o a keratin pearl FIGURE 21.17 Reactive mesothelial cells may degenerate and swell These three cells have abundant multivacuolated cytoplasm and large nuclei with prominent nucleoli CH AP TER : Se ro u s Me m b n e s 591 FIGURE 21.18 When markedly reactive mesothelial cells orm irregular groups and combine with degenerating orms, they may mimic the appearance o a mucin-producing adenocarcinoma The types of terminal carbohydrate groups of membrane proteins and lipids can also be characterized with lectins, which have speci c and discrete ranges of sugar group af nities Concanavalin A mesothelial cell reactivity indicates the presence of terminal groups that are either mannose or glucose Immunohistochemistry Immunohistochemical studies of serous membranes have shown that mesothelium expresses a complex and varied phenotype with overlap of other normal tissues and many malignancies The great majority of benign mesothelial proliferations express several keratins, especially AE1/AE3, CK8/18 (Cam5.2), CK19, CK5/6 and CK7 that can be detected with monoclonal antibodies immunoreactive with the small, acidic, type I keratins (26) (Figure 21.19) (42) Mesothelium does not express CK20 (27) Ovarian epithelial tumors express a spectrum of keratins similar to that of mesothelium (28) FIGURE 21.19 Keratin expression in mesothelium and detached mesothelial cells, stained with a cocktail o monoclonal antibodies (AE1/AE3) FIGURE 21.20 Calretinin Immunohistochemical staining o both nucleus and cytoplasm in benign mesothelial cells Mesothelial cells frequently and preferentially express calretinin, podoplanin, HBME-1 and thrombomodulin, as well as WT-1 Vimentin and desmin are also expressed by reactive mesothelium, especially when in spindle form Calretinin, a calcium-binding protein of 29 kDa similar to S-100 protein, is found not only in both the nucleus and the cytoplasm of reactive and neoplastic mesothelia but also in some adenocarcinomas (29–32) (Figure 21.20) Cytokeratin 5/6 is found in the cytoplasm of most mesothelial cells and squamous cell carcinomas, but few adenocarcinomas (33) WT-1, a product of Wilms’ tumor gene, is found in the nucleus of reactive and neoplastic mesothelia and in ovarian surface epithelium and tumors derived therefrom (34) (Figure 21.21) D2-40, an antigen characteristic of lymphatic endothelium, is also expressed by mesothelial FIGURE 21.21 WT-1 immunoreactivity in benign mesothelium is nuclear (original magni cation 40×) 592 S E C TIO N VI: Th o x a n d Se ro u s Me m b n e s FIGURE 21.22 D2-40 immunoreactivity in benign mesothelium is predominantly membranous cells with a high sensitivity (Figure 21.22), but it also marks ovarian serous carcinoma (35) Thrombomodulin, a transmembrane glycoprotein, gives a membranous stain in not only about half the mesotheliomas but also in some adenocarcinomas Mesothelium less frequently and less reliably expresses other antigens, including mesothelin, N-cadherin, E-cadherin, epithelial membrane antigen (EMA), Her2/Neu and EGFR (36) Mesothelial cells usually lack the glycoproteins detected by antibodies to CEA, MOC-31 and BER-EP4 and the determinant detected by Leu-M1 (CD15) (37–40) Latza et al (41) and Sheibani et al (42) reported that BER-EP4 was used to distinguish malignant epithelium (adenocarcinoma) from malignant mesothelioma, but Gaffey et al (43) and Otis (44) reported BER-EP4 immunoreactivity in high proportions of both benign and malignant mesothelial tumors, as well as adenocarcinomas The tissue speci c nuclear transcription protein TTF-1 is important in the embryogenesis of thyroid and lungs and is found in nuclei of pneumocytes and many adenocarcinomas of the lung, but not in mesothelium (45) Overlap between reactive and neoplastic mesothelia in the expression of even a panel of antibodies leaves only the demonstration of invasion of parietes or organs to rm the diagnosis of malignant mesothelioma in most cases The diagnosis of mesothelioma in situ requires demonstration of invasive mesothelioma elsewhere in the same specimen or in a subsequent specimen The plasticity of the immunophenotype of mesothelial cells is demonstrable in abnormal states Although mesothelium normally lacks sex steroid receptors, reactive mesothelium adjacent to endometriosis expresses focal immunoreactivity for estrogen and progesterone receptors (46) Furthermore, reactive mesothelial cells can express FIGURE 21.23 Keratin (AE1/AE3) immunoreactivity o proli erating submesothelial spindle cells the muscle cell cytoskeleton proteins, desmin and musclespeci c actin (47) There is experimental evidence that the pattern of intermediate lament expression by mesothelial cells is dependent on shape and cell–cell interaction Induction of spindle morphology inhibits keratin synthesis In contrast, induction of an epithelioid morphology (eg, with retinoids) stimulates keratin synthesis and inhibits vimentin synthesis; the ability of cells to respond in this manner also depends on the presence of cell–cell interactions (48) (Figures 21.23–21.26) FIGURE 21.24 A patient with severe rheumatoid arthritis and pleural e usion with f orid reactive mesothelial hyperplasia o the pleura, which may be di cult to distinguish rom neoplastic proli eration The proli erating mesothelial cells may become entrapped in the brous tissue o organization and may mimic invasion CH AP TER : Se ro u s Me m b n e s 593 pleura and in the visceral pleura The other organelles found in mesothelial cells are not speci c for them Junctions of all types are found—tight junctions that serve as a barrier to certain molecules, gap junctions for cell–cell transport, and desmosomes for cell–cell adherence Intermediate laments are somewhat prominent; although they not aggregate into bundles, they are often arranged in a perinuclear, circumferential distribution (Figures 21.29, 21.30) SUBMESOTHELIALLAYER Much of the submesothelial layer is composed of collagen, elastin, and other extracellular proteins Normally, the submesothelial layer contains few cells, and most of these are broblasts, but during reactive processes, the submesothelial layer may become much more prominent as myo broblasts, in ammatory cells, and capillaries proliferate there Histochemistry FIGURE 21.25 The reactive mesothelium in this photomicrograph is rom a hernia sac o an 18-month-old boy It is composed o proli erating epithelioid cells on the sur ace and subjacent spindle-shaped cells that give the impression o proli erating broblasts Ultrastructure Numerous long microvilli (Figures 21.27, 21.28), measuring up to µ m in length and 0.1 µ m in diameter, are present and are more numerous in caudal portions of the parietal The main constituents of the submesothelial tissue are glycosylated proteins, including glycosaminoglycans Since the majority of carbohydrate groups are negatively charged (as a result of an abundance of hyaluronic acid and other acidic groups), this extracellular matrix stains in a manner characteristic of acidic mucoproteins; that is, it is Alcian blue positive That staining intensity can be diminished by treating the section with hyaluronidase before histochemical staining is evidence that hyaluronic acid groups are responsible, in large part, for the intensity of staining (21) FIGURE 21.26 The reactive peritoneum shown in Figure 21.25 is shown at higher magni cation in H&E on the le t On the right, immunohistochemical stain or keratin (AE1/AE3) illustrates that both the epithelioid and spindle cells are keratin positive, indicative o their mesothelial di erentiation 594 S E C TIO N VI: Th o x a n d Se ro u s Me m b n e s FIGURE 21.27 Mesothelial cells with their elongated microvilli, cover the sur ace o the serosa The subjacent stroma is composed o collagen and broblasts FIGURE 21.29 Ultrastructure o a mesothelial cell Intermediate laments are arranged in a perinuclear distribution FIGURE 21.28 EM o a cluster o detached mesothelial cells within a pleural e usion Cytoplasmic lipid droplets impart a vacuolated appearance to some cells Note the numerous long microvilli, which impart the “ uzzy” appearance to these cells at the light microscopic level FIGURE 21.30 High magni cation o the luminal aspect o two mesothelial cells Note the small tight junction, subjacent desmosome, and the cytoskeletal laments within the microvilli 1322 In d e x Pancreas (continued) development of, 780–785, 782f ductal cells, minor alterations in, 799–803 ducts, 788–791, 788f–791f ducts, and duodenum, 788–791 enzymes, 786 extrainsular endocrine cells, 794–795 fetal, 783f brosis, 805–810 gallbladder agenesis, 783 heterotopia, 783–785 heterotopic pancreatic tissue, 785f islet cells, minor alterations in, 803–805 islet of Langerhans, 791–794 lipomatosis, 810, 810f location and relationship, 777–780, 778f, 779f luminal necrosis, 800 microscopic features, 785–797 minor alterations, 798–810 neuroendocrine tumor, 785 organogenesis, 780–782 pancreaticoduodenal veins, 779 pancreatic polypeptide, 793, 795 pancreatic tissue, 783, 784 pancreatitis, 805–810 regions of, 780 ring, 783 ventral, 784 Pancreatic acinar metaplasia, 645 Pancreatic acini, 768 Pancreatica magna, 779 Pancreatic heterotopia, 784 Pancreatic intraepithelial neoplasia (PanIN), 800f, 801f Pancreatic metaplasia, 610, 611f Pancreatic tissue, 192 Pancreatoduodenal artery, 778 Pancreatoduodenal sulcus, 778 Pancreatoduodenectomy, 759 Pan-cytokeratin antibodies, 47 Pancytokertain (CAM5.2), 535f Paneth cells, 978 Paneth-like granules, 617 Paneth’s cells, 644, 652, 653f, 659, 700, 701f of colon, 679f, 680, 680f right colon with, 680f Panniculitis, 195 Papilla, circumvallate, 448f Papillae, 617 Papillary basal layer (PBL), 616 Papillary collecting duct, 948 Papillary dermis, 5, 15–16 Papillary muscles, of heart, 574, 574f, 575f Papilloma, inverted, 978f Papillomatosis, 41, 45 Parabasal cells, 1077 Paracortex, 820, 825–826, 826f See also Lymph nodes changes in, 829–830 (see also Lymph nodes) epithelioid venules, 825 immunohistochemistry of, 827f interdigitating dendritic cells, 825–826 lymphoid cells, 826, 827f Paracrine cells, 1260 Para bromin, 1214, 1215f Parafollicular cells See C cells Paraganglia, 763 aging changes, 1289 anatomy, 1284–1285 autonomic nervous system, 1277 developmental changes, 1283 differential diagnosis, 1294 distribution of, 1279–1281, 1279f, 1280f embryology, 1281–1283, 1282f function, 1288–1289 gallbladder, 1281, 1290f gender differences, 1289 gross features and organ weights, 1284 history and nomenclature, 1277–1278 immunohistochemical artifacts, 1293–1294 immunohistochemistry, 1289–1293 light microscopy, 1285–1286 phenotypic plasticity, 1284 physiologic role of, 1288–1289 postnatal changes, 1283 special procedures, 1289–1294 specimen handling, 1294 sympathetic vs parasympathetic, 1278–1279 ultrastructure, 1286–1288 urinary bladder, 1279 Parakeratosis, 7, 38 foci of, 465 Paranasal sinuses, 433, 436–437, 437f, 456 Paraneurons, 1257 Parasitic nodules, 1202 Parathyroid gland adipose tissue, 1218 calcium metabolism, 1215–1216 cell nests, 1216 chief cells, 1209, 1210f, 1211f, 1214 ectopic tissue, 1217 embryology, 1210–1212, 1210f–1212f genes in, 1213t gross appearance, size, and shape, 1217, 1217f histology, 1217–1224 historical review, 1209 lymphatics, 1218 molecular biology, 1212–1215 neoplasia, 1212–1215 number and location of glands, 1216–1217 oxyphil cells, 1217, 1221f parathyroid hormone, 1215–1216 phosphate hormone, 1215–1216 phosphate metabolism, 1215–1216 secretory cycle, 1221, 1222f thyroid glands, parathyroid tissue in, 1216, 1217 tissue of, in thymus gland, 1210, 1210f vasculature, 1217 Parathyroid hormone (PTH), 94, 1210 synthesis, 1215 Parathyroid hormone–related protein (PTHrP), 100 Parathyroid tissue, of thyroid gland, 1200 Paraventricular nuclei (PVN), 343 Paraxial mesoderm (PM), 903, 912 Parenchyma, 928 Parenchymal cholestasis, 756 Parenchymal injury, 318 Parenchymal scar, incidental, 526f Parietal cells, 641 Parietal epithelial cells, 936–937 See also Glomerulus Parietal mesoderm, 585 Parietal pericardium, 565 Parietal pleura, 585, 586 Parks syndrome, 1056 Parotid gland, 477–479 Parotid lymph node, 437 Pars broreticularis, Pars accida, 402 Pars tensa, 402 Partial atrophy, 999 Par tuberalis, 364 Parturition and oxytocin, 353 PAS-positive basement membrane, 7f, 11 PAS-positive, diastase-resistant (PASD), 13, 748, 749f Patent foramen ovale, 568 Pax2, 909 Pax-6, 344 PAX 8, 597, 1185 Pdx1 protein, 782 Peanut agglutinin receptor antigen (PNA-r), 549 Pecten, 710 See also Anal canal Pectinate muscles, 568, 569 Pediatric kidney, 892 anatomy, 892 development, 892 histology, 892 Pedunculated lipo broma, 196 Pemphigoid antigens, 45 Pencil cells, 765 Pendrin, 948 Penile erection, 1040 Penile shaft, 1034–1036 anatomical levels of, 1034 anatomic features of, 1034–1035, 1034f, 1035f microscopic features of, 1035–1036 Penile urethra, 1039f Penis, 1027f arteries, 1040 cancer, 1032, 1035 constituents of, 1027 coronal sulcus, 1030, 1030f distal, 1027–1034 distal urethra, 1037–1040 foreskin, 1030–1034, 1031f–1033f glans, 1027–1029, 1028f lymphatics, 1040–1041 nerves, 1041 penile shaft, 1030, 1034 proximal, 1034–1036 veins, 1040 Peptidases, 650 Peptidergic neural bers, 659 Peptidylamidaglycolate lyase (PAL), 1264 Peptidyl-glycine alpha-amidating monooxygenase (PAM), 1264 Peptidyl-glycine alpha-hydroxylating monooxygenase (PHM), 1264 Percutaneous coronary angioplasty (PTCA), 248 Periadnexal dermis, 15 Perianal apocrine glands, 709 Perianal hematoma, 721 In d e x Perianal thrombosis, 721 Periarteriolar lymphoid sheath (PALS), 838 Periaxin, 274 Periaxin–DRP2–dystroglycan complexes, 275 Peribronchial lymph node, 531 Peribronchiolar metaplasia, 508 Pericardium, 565–566, 565f See also Heart applied anatomy, 566 parietal, 565 visceral, 565 Perichondrium, mesenchymal stems cells of, 98, 98f Pericytes, 136 Periderm, Perifollicular zone (PFZ), 838, 842–843 Perilymph, 420 Perimenopausal and postmenopausal years, 1101–1102 Perimysium, 219 Perineurial cells, 265 Perineurioma, 284 Perineurium, 265–267 Perineuronal satellitosis, 317f Periodic acid-Schiff diastase-resistant (PAS-D), 753 Periodic acid-Schiff (PAS), 7, 184, 305, 356, 376, 444, 480, 508, 589, 614, 614f, 636, 650, 650f, 699, 738, 738f, 786 Perionychium, 57 Periosteal lipoma, 199 Periosteal vessels, 99 Periosteum, 92 Peripheral nerve compartments, elements of, 265f bers, 269 histologic techniques for, 270t sheaths and compartments, 264f Peripheral nervous system anatomy, 263–264 axonal degeneration and regeneration, 279–281, 279f, 280f axons, growth of, 262–263 axoplasmic ow, 272 blood supply of, 269 CNS intradural elements of, 274 development of, 261–262 endoneurium, 268–269 epineurium, 265 general pathology, 279 histology, immunocytochemistry, and ultrastructure, 264–278, 266f–267f hypertrophic neuropathy, 282 intradural elements of, 327–330, 329f Klebs, periaxonal space of, 272–273 myelin, 273–275 myelinated axons, 270–272 nerve bers, 269–270 nerve sheath, 264–265 nodes of Ranvier, 275–276 pathology of, 278–288 perineurium, 265–267 peripheral neuropathies, 279 Schmidt–Lanterman incisure, 275 Schwann cells and myelination, 263 segmental demyelination and remyelination, 281–282, 282f, 283f specimens, 278–279, 278f traumatic lesions, 282–284 tumors of, 284–288 unmyelinated axons, 276–278, 277f Peripheral neuropathies, 279 Peripheral skeleton, 85 Peritoneal mesothelium, 597 Peritoneum, 585 Periurethral gland, 1049 Perivascular astrocytic foot process, in autolysis, 316f Perivascular brosis, 367f Perivascular in ammation, 17 Periventricular nucleus, 354f Perlecan, 452 Perls’ acid ferrocyanide method, 858, 873 Pernicious anemia, 639 Persistent neonatal hyperinsulinemic hypoglycemia (PNHH), 803 Pertinax bodies, 39 Petrosquamous suture, 404 Petrous apex, cholesteatoma of, 425 Peutz–Jeghers syndrome, 449 Peyer’s patches, 443, 661, 701 Peyronie’s disease, 148, 1035 p16 gene, 596 p53 gene, 543 Phagocytic macrophages, Phagocytic reticular cells, 858–860, 858f Phagocytosis, 836 Phakomatoses, 287 Phalanx, 32 Pharyngeal bursa, 438 Pharyngeal granulations, 438 Pharyngeal tonsils, 438 Pharyngotympanic tube, 400, 403 Pharynx anatomy, gross, 470–471, 471f anatomy, microscopic, 471–474, 472f, 473f de nition and boundaries, 469–470, 469f, 470f embryology, 470 lymphatics, 474 neural, vascular, and lymphatic components, 474 piriform recesses, 470 vasculature, 474 Phenylethanolamine-N-transferase (PNMT), 1292 Pheochromocytes, 1245 Pheochromocytoma, 1278 Pheomelanin, 12 Phimosis, 1032 Phosphatase inhibitor calyculin, 140 Phosphate metabolism, 1215–1216 Phosphatidylinositol 3-kinase (PI3K), 904 Phosphoneuro lament (pNF), 954 Phosphosomes, 866 Phrenoesophageal ligament, 609 Physiology follicular cells, 1191–1192 gallbladder, 760 small intestine, 648 Pia-arachnoid, 332–333 Pie crust artifact, 229, 229f Pigment donation, de ned, PI3K-AKT pathway, 165 Pilar disk, 12 1323 Pilar unit apocrine gland, 15 eccrine glands, 13–15 hair follicle, 10–13 sebaceous glands, 13 Pilocytic astrocyte, 310 Pilocytic astrocytoma, juvenile, 312 Pilosebaceous follicle, 15 Pilosebaceous glands, 45 Pilosebaceous units, 19 skin of face with, 19f p53 immunostain, 54f Pineal gland, in central nervous system, 320–321, 322f Pineal histology, 323f Pineal immunohistochemistry, 323f Pineocytes, 321 Pineocytoma, 320 Pinna, 400 Pinocytotic vesicles, 184 Pi (π ) granules of Reich, 273 Piriform fossa, 461 Piriform sinuses, 471 Pit cells, 742 Pit-1 favor prolactin (PRL), 344 Pitting, 845 See also Spleen Pituicytes, 368, 368f Pituicytomas, 370 Pituitary adenomas, 344f, 357, 363, 369 Pituitary and sellar region, 349f–352f adenohypophysis, 355–368 age-related changes, 367–368 corticotroph cells, 361–362 folliculostellate cells, 364 gonadotroph cells, 363–364 gross anatomy, 345–353 lactotroph cells, 360–361 normal morphology, variations in, 365–367 par tuberalis, 364 somatotroph cells, 357–360 thyrotroph cells, 362–363 bony sella, 345–346 differential diagnosis, 369–370, 370f embryology, 343–345, 344f hypothalamus, 353–355 meninges, 346–347 neurohypophysis, 368–369 pituicytes, 368, 368f pituitary adenomas, 344f, 357, 363, 369 pituitary hormones, 343, 344, 355t, 357, 360 pituitary stalk, 345, 346f, 349, 353, 356f, 364 secretory cells, 359t, 363f, 364, 366 vasculature, 347–353 arterial supply, 348–350 cavernous sinuses, 347–348, 347f, 348f hypophysial portal system, 350–353 Pituitary axis hormones, 355t Pituitary follicle, electron micrograph of, 365f Pituitary homeobox factor (Ptx1), 344 Pituitary homeobox factor (Ptx2), 344 Pituitary hormones, 343, 344, 355t, 357, 360 and hypothalamic hormone, 355t Pituitary stalk, 345, 346f, 349, 353, 356f, 364 1324 In d e x Pityrosporum, yeasts of, 11f Placenta amnion and chorion, 1160–1165, 1160f–1163f chorionic vasculature pathology, 1159, 1159f chorionic vasculature, rami cation of, 1158–1159, 1158f decidua, 1174–1177 embryology, 1159–1160 gestational trophoblastic disease, 1177–1179 maturity, determination of, 1169 membranes, 1159–1165 multiple gestation, 1165–1166 recording format, 1151t storage, examination, and processing, 1149–1152 umbilical cord, 1152–1158 villi, 1166–1173 Placenta–like alkaline phosphatase (PLAP), 1012 Placental site nodule (PSN), 1100, 1179 Placental site trophoblastic tumor (PSTT), 1100, 1178 Planar cell polarity (PCP), 907 Plasma cells, 824, 881–883, 882f, 883f Plasma membranes (PM), 1123 Plasminogen activator inhibitor-1 (PAI-1), 183 Plasminogen activator inhibitor type (PAI-2), 51 Plasmocytoid cell, 486 Platelet-derived growth factor- B (PDGF-B), 914 Platelet-derived growth factor (PDGF), 165 Platelet peroxidase (PPO), 878 Pleomorphic adenoma, 489 Pleomorphic adenoma gene (PLAG1), 444 Pleomorphism, 313 Plethora, 139 Pleura, 515, 515f, 533 cervical, 585 empyema, human chronic granulation tissue, 142f functional anatomy of, 586 parietal, 585, 586 visceral, 585, 586f, 587f Plicae, 316 circulares, 647 Plica semilunaris, 381–382 PLS regression, 40 Pneumocystis carinii, 23 Pneumothorax, 519f Podocalyxin, 935 Podocin, 913 Podocytes, 928, 933–936, 933f–935f Podocyturia, 920 Podoplanin, 591 Polsters, 1040 Polyclonal anti-carcinoembryonic antigen (pCEA), 740 Polyhedral eosinophilic keratinocytes, Polymerase chain reaction (PCR), 26, 466, 751 Polymorphonuclear cells (PMN), 1165 Polymorphonuclear leukocytes, 762 Polytef (polytetra uoroethylene), 1192 Pores of Kohn, 512 Portal broblasts, 742 Portal tracts, of liver, 742, 742f, 743f Portal vein, 766 thrombosis, 743 Post-atrophic hyperplasia, 999 Postovulatory date (POD), 1103 Postovulatory day (POD), 1095 Postsynaptic (POS), 216 Post-transplant lymphoproliferative disorders (PTLD), 579 p53 protein, 426 p63 protein, 426 P-63 protein, 478 p422 protein, 188 Prague system, 622 Preadipocytes, 187 Precapillary sphincters, 579 Pregnancy and adenohypophysis, 367 atretic follicles in, 1140f breasts, 76–77 cells, 360 cervix during, 1085–1086, 1086f fallopian tube in, 1110, 1110f related changes, 1106–1108 Premenarchal uterus and fallopian tubes, 1072–1073, 1073f Prenatal fetal circulation, 564 See also Heart Preperitoneal broadipose tissue, 586 Prepubertal ovaries, 1120 Prepubertal testis, 1010–1013 Presbycusis, 427–428 Presynaptic (PRS), 215 Pretubular aggregate (PTA), 895 Prickle cell layer, 6, 464 Primordial eccrine epithelium, Primordial follicles, of ovary, 1129–1130 histology, 1129–1130, 1129f ultrastructure, 1130 Primordial germ cells, 1012 Progesterone, 183, 1066 Progesterone receptor (PR), 72, 1191 Programmed cell death, 214 Progressive multifocal leukoencephalopathy (PML), 313 bizarre reactive astrocytes of, 315f Prolactin cells, 1271 Proliferating cell nuclear antigen (PCNA), 1077 Proliferative cells, 1089 Promegakaryocytes, 876 Promyelocytes, 865 Pronephros, 892–893 Pronormoblasts, 872 Proopiomelanocortin (POMC), 344, 361, 1267 Prophet of Pit-1 (Prop-1), 344 Propidium iodide (PI), 47 Prospermatogonia, 1011 Prostaglandin F1, 137 Prostatectomy specimens, 989–990, 990f Prostate gland anatomy, 990–995, 990f–994f anterior bromuscular stroma and prostatic capsule, 992–993 apical one-third of the prostate, 990–991, 991f basal one-third of the prostate, 992, 992f cancer, 990 development of, 987 embryology, 987, 988f extraprostatic tissues, prostatic innervation and vascular supply, 993–995, 994f glandular prostate architectural patterns, 995–996, 996f cytologic features, 997–998, 997f, 998f relationships of, 988–989, 988f, 989f intraepithelial neoplasia, 996 McNeal’S zonal anatomy, 988–989, 988f middle one-third of the prostate, 991 needle biopsies, 1000–1001 non-glandular components of, 992–995, 993f normal histology, deviations from, 998–1000, 999f, 1000f prostatectomy specimens, 989–990, 990f prostatic capsule, 992–993 transurethral resections, 1000–1001, 1001f Prostate-speci c antigen (PSA), 1039 Prostatic acid phosphatase (PAP), 995 Prostatic intraepithelial neoplasia (PIN), 998 Proteases, 268 Protein gene product 9.5 (PGP 9.5), 1263 Protein kinase C (PKC), 904 Proteins, in bone, 93–94 Proteoglycans (PG), 109, 572, 595 Protogranules, 937 Proto-myo broblast, 138 development of, 138 Proximal esophagus, 609f, 610f, 620f Proximal muscles, 217 Proximal nail fold (PNF), 32 The proximal nail groove, 32 Proximal nail matrix (PNM), 37 Proximal penis, 1034–1036 anatomical levels of, 1034 anatomic features of, 1034–1035 microscopic features of, 1035–1036 Proximal tubule, 938–942, 939f–942f See also Kidney Prussian blue histochemical stain, 521 Psammoma bodies, 391, 391f, 597 Psammoma body, 595, 596f Pseudointima, 249 Pseudolipoma, 192 Pseudolipomatosis, 202, 688, 688f Pseudomelanosis duodeni, 659 Pseudonecrosis etiologies, 336t Pseudounipolar cells, 264 Psoralen-UV-A (PUVA), 40 Psoriasis, 20 nail, 40 Pterygium inversum unguis, 38 Pterygoid plexus, 437 Ptyalin, 480 Pudendum femininum, 1045 Pulmonary arteries and veins, 242–243 See also Blood vessels Pulmonary corpora amylacea, 528f Pulmonary edema, 535f Pulmonary lobule, 512f Pulmonary neuroendocrine cells (PNC), 524 Pulmonary vasculature, 514f Pulmonary venous sleeves, 569 Pulmonary vessels, histologic features of, 244t Pulmonic valve, 571 In d e x Pulp stones, 452 Pulsion diverticulum, 611 Purkinje cell, 298, 301, 302 layer, 297 Purkinje neurons, 310 Pyelitis, 977 Pyloric glands, 617 Pyloric metaplasia, 643 Pyramidal cells, 301 Q Quiescent cells, 739 R Rab proteins, 1265 Rack of test tubes”, 675 Radical inguinal–femoral lymphadenectomy, 1055 Radical prostatectomy, 989 Radioautography, usage of, 58 Radiofrequency intravascular ultrasonography, 239 Raisionoid, 1077 RANK ligand (RANKL), 96 RANK (Receptor activator for nuclear factor κβ ), 96 Rapid trichrome (RTC), 217 Rappaport acinus, 736 Rappaport acinus zone, 753 Rathke’s cleft, 370 cyst, 361 remnants, 357 Rathke’s pouch, 343, 472, 489 Rathke’s pouch homeobox (Rpx), 344 Reactive astrocytosis, 313f Reactive mesothelium, 595–599, 595f endosalpingiosis and endometriosis, 597–598, 597f, 598f brous pleurisy, 598, 598f multilocular peritoneal inclusion cyst, 598–599, 599f reactive mesothelium vs carcinoma, 596–597 reactive vs neoplastic mesothelium, 596, 596t, 597t Recurrent arteries, 1010 Red cell precursors, 871–876 aspirate smears, 871–872, 871f biopsy sections, 872f, 873 cytochemistry, 873 dyserythropoiesis and ineffective erythropoiesis, 875–876, 875f ultrastructure, 873–875, 874f Red muscle, 217–218 Red pulp, 839f, 840–841, 840f See also Spleen Reed–Sternberg cells, 830 Reelin (RELN), 426 Re ux-associated squamous hyperplasia (RASH), 624, 624f Refsum’s disease, 282 Reichert’s cartilage, 401, 404, 443 Reinke crystalloids, 1009 Reinke’s space, 465, 466f Reissner’s membrane, 417 Remak cells, 277 Renal corpuscle, 928 Renal cortex, architectural regions of, 926f Renal interstitium, 949–951, 950f Renal papilla, 975f types of, 925 Renal pelvis, 925 anatomy, 974 embryology, 972 formation of, 893–894, 894f lamina propria, 979–980 microscopic anatomy, 974–975, 974f muscularis propria, 980–983 renal anatomy, 974–975 renal papillae, 974 urothelium variants and benign proliferations, 976–979 Renal sinus, 925 Renal vasculature, 951–953, 951f–953f Renal vesicle (RV), 893 Renin–angiotensin system, 906 Reserve cells, 1007 Resorption lacunae, 857, 857f Resorption vacuoles, 1189 Respiratory bronchiolitis, 522f Respiratory epithelial adenomatoid hamartoma (REAH), 454 Respiratory epithelium, 453 Respiratory tract epithelia, 510f Restenosis, 248 Rests of Malassez, 452–453, 452f Rests of Serres, 452–453 See also Mouth Rete ovarii, 1143, 1143f Rete ridges, Rete testis, 1014–1015, 1014f Reticular dermis, 4, 15–16 Reticularis cells, 1241 Reticulin framework, 1092 Reticulin stains, of lungs, 516 See also Lungs Reticulocyte, 872 Retina, 387–390 artifacts of, 390–391, 390f cellular components of, 387, 387f external limiting membrane, 388 at preparation of, 390f histologic variations, 389f internal limiting membrane, 388 macula lutea, 388 ora serrata, 390 ora serrata marks, 387f Retinaldehyde dehydrogenase (Raldh2), 903 Retinoic acid-inducible gene-1, 50 Retinoic acid (RA), 903, 1005 Retractile mesenteritis, 195 Retroperitoneal xanthogranulomatosis, 195 Retropharyngeal nodes, 437–438 Rhabdomyosarcoma, 288 Rheumatic syndromes, 122 RhoA activity, 140 RhoA/Rho-kinase signaling, 140 Ribonucleic acid (RNA), 280, 637 Rickettsial infection, 318 Right atrium, of heart, 568–569, 569f Right ventricle, of heart, 569–571, 570f applied anatomy, 570–571 Ring bers, 840, 840f Ring of Nemiloff, 276 Ring of Ranvier, 100, 100f, 101f 1325 Rivinus’ ducts, 479 Rod cells, 318 Rokitansky–Aschoff sinuses, 763, 763f Roman arches, 996 Romanowsky method, 851 Romanowsky stain, 797 Romanowsky stained smears, 866 Rosenmüller’s fossa, 470 Rosenthal ber, 310, 312, 314f Rough endoplasmic reticulum (RER), 786, 787, 855 Rugae, 634 Runx2 signaling, 94 Russell bodies, 825 S Saccule, 414, 414f, 417–418 Sacculi of Beale, 767 Salivary glands major aging changes, 489–490, 490f apoptosis, 477 correlative normal and neoplastic histology, 492–494, 493f, 494f ducts, 481–482, 481f–483f embryology and postnatal changes, 477–479, 478f heterotopic salivary tissue, 488–489, 489t immunohistochemistry, 494–495, 495t light microscopy, 479 lymphoid tissue, 486–488, 488f myoepithelial cells, 484–486, 485f, 486t reactive changes, 490–492, 491f, 492f sebaceous glands, 483–484, 484f secretory units, 480–482, 480f–483f specimens, 495–496, 496f of mouth, nose, and paranasal sinuses, 445t primary function of, 477 SAMRCB1 gene, 288 Sanderson’s polster, 1188f, 1192, 1192f S-100 antigen, 1054 Santorini, duct of, 768 Sarcomatoid carcinomas, 971 Sarcoplasmic reticulum (SR), 221 Satellite cells, 221–222, 264, 1285 Scala media, 412 Scar carcinoma, 157 Scarpa’s ganglion, 415 Schatzki’s ring, 607, 612, 613f Schaumann bodies, 527, 529f Schlemm’s canal (SC), 380f, 393 Schmidt–Lanterman incisure (S-L I), 274, 275, 279 Schneiderian membrane, 470 Schwalbe’s ring, 380, 380f Schwann cells, 4, 17, 273, 329, 418, 419f, 578, 703, 705f, 706f in myasthenia gravis, 278 and myelination, 263 in schwannomas, 286f S-100 protein in, 273 Schwannomas, 262, 268, 284 Schwann cells in, 286f Schwannomatosis, 288 1326 In d e x Schwannomin, 288 Schwann sheath, 264 Sciellin, 46 Sclera, 378–379, 379f components of, 378 Scleral spur, 381 Sclerotic glomeruli, 922 Sebaceous glands, 4, 483–484, 484f, 610, 610f and peripheral germinative cells, 12f Secretory cells, 359t, 363f, 364, 366, 1089– 1090 See also Pituitary and sellar region morphologic and functional features of, 359t Segmentectomy, 70 Sella, empty, 347 Sella turcica, 345 Sema3a-neuropilin1, 906 Semaphorins, 906 Semicircular canals, 414–415, 417–418 Semilunar valve, 573 of heart, 571–572, 571f Seminal vesicles, 1018–1019, 1018f See also Testis and excretory duct system Seminiferous tubules, 1004–1005, 1004f See also Testis and excretory duct system Semithin, 850 Senile amyloid, 534 Senile emphysema, 534 Senile scleral plaques, 379 Sensorineural hearing loss, cause of, 428f Septa, 838 Septa of Berlin, 951 Seromucinous glands, 454, 466, 467f Serosa, 620–621 Serosa and subserosal region, 657, 657f See also Small intestine Serotonin, 652 Serous membranes anatomy, 585–586 anatomy, functional, 586–588, 587f functions, 585 mesothelial cells, 588–593, 588f–591f pleural uid, 587, 587f, 588, 596 submesothelial layer, 593–595 ultrastructure, 593, 594f mesothelial and submesothelial cells, 595 reactive mesothelium, 595–599 submesothelial layer, 593–595 ultrastructure, 593, 594f Sertoli cells, 364, 1005–1006 with Charcot–Böttcher crystalloids, 1005f seminiferous tubule with, 1005f Serum amyloid A, 751 Sexually transmitted diseases (STD), 1031 Sézary syndrome, 830 Sharpey’s bers, 110 Sheathed capillaries, 838 Sheath of Henle, 216 Shotgun proteomic analysis, of human nail plate, 34 Shrapnell’s membrane, 402, 424 Shwachman’s syndrome, 192, 810 Sialadenosis, 491 Sialase digestion, 589 Sialolipoma, 444 Sialomucin, 13, 641, 644, 651 Sick lobe hypothesis, 70 Sideroblasts, 873 Silicone substrates, 139 Silicotic nodules, 532 Simple atrophy, 999 Single nucleotide polymorphisms (SNP), 427 Sinoatrial (SA) node, 575, 576f Sinonasal adenocarcinoma, lowgrade, 454 Sinuses, 826–828, 827f See also Lymph nodes piriform, 471, 471f vascular transformation of, 830 Sinus-lining cell, 827 Sinus of Valsalva, 572 Sinusoidal changes, 830 See also Lymph nodes Sinusoidal dilatation, 753 See also Liver Sinusoidal lining cells, 740–742, 741f, 742f See also Liver Sinusoids, 241 Sinus tympani, 406 Sjögren’s disease, 444 Sjögren’s syndrome, 439, 488 Skeletalized graft, 248 Skeletal muscle aging, 225–227 anatomy, 214–216 apoptosis, 214 artifacts, 227–229 biopsy techniques, 231 differential diagnosis, 229–231 embryology, 211–213, 212f bers, denervation of, 226 ber typing, 218t function, 223–225 gender differences, 225–227 immunohistochemical identi cation of proteins in, 223t light microscopy, 216–220 postnatal and developmental changes, 213–214 special techniques, 222–223 specimen handling, 231–232 training and exercise, 225–227 ultrastructure, 220–222, 221f Skeleton, 85, 86f acral, 85 axial, 85 peripheral, 85 Skene’s ducts, 1048 Skene’s gland, 1046 Skin age, histologic differences with, 18 anatomic sites, histologic variations with, 19, 19f artifacts, 22 biopsies, pathologic changes in, 20–21 blood vessels, lymphatics, nerves, and muscle, 17 cancer, 8–9 composition of, embryology, 3–5 excisional biopsies, 21 functions of, histologic variations, 19–20 histomorphology, 5–18 light microscopy, 6–8 neuroendocrine cells, 26 pathology interpreted as normal, 20–21 punch and shave biopsies, 21 specimen handling, 21 staining methods, 22–26 subcutaneous tissue, 16–17 Sky cells, 837 Sloughing esophagitis, 626, 626f Smad4 protein, 751 Small bowel, distinctive regional characteristics of duodenum, 657–659, 658f ileum, 660–662, 661f, 662f jejunum, 659–660 Small granule-containing (SGC) cells, 1280 Small intensely uorescent (SIF) cells, 1280 Small intestine age-related changes, 662–663 diet, 662–663 duodenum, 647, 657–659, 658f environmental factors, 662 gross anatomy and surgical perspective, 647–648 histology, 648 mucosa, 649–655, 649f–653f muscularis externa, 656–657, 656f serosa and subserosal region, 657, 657f submucosa, 655–656 ileum, 647, 660–662 jejunum, 647, 659–660 lymphoid proliferations, 663–664 malabsorptive states, 664 metaplastic and heterotopic tissue, 663, 663f morphologic changes, 664 physiology, 648 specimen interpretation and common artifacts, 665–667, 665f, 666f specimen procurement and processing, 664–665 surgical perspective, 647–648 Smoking, subpleural emphysematous change in, 518f Smooth muscle actin–positive (SMA positive), 840 Smooth muscle actin (SMA), 26, 255, 255f, 444, 724, 981f Smooth-surface synaptic-type vesicles (SSV), 1264 SNAP receptors, 1290 SNARE protein, 1265 Sodium iodide symporter, 1191 Solid cell nests (SCN), 1186 Solid cell rests, 1198 See also Thyroid gland Solitary circumscribed neuroma, 284 Soluble N-ethylmaleimide–sensitive fusion attachment protein receptor (SNARE), 1216 Somatostatin, 355, 652, 1196 receptors, 1266 Somatotroph cells, 357–360, 359f Somatotrophs, 345 Somatotropin-release inhibiting factor (SRIF), 355 Sommer’s sector, 300 Sonic hedgehog (Shh), 782, 1213 Sophora Japonica agglutinin receptor antigen (SJA-r), 549 Sox10, 262 In d e x Space of Disse, 741 Spatium subdurale, 332 Spermatids, 1008 Spermatocytes primary, 1007 secondary, 1007–1008 Spermatogenesis, 1006 steps in, 1006f Spermatogonial stem cells (SSC), 1007 Sphincter of Oddi, 745, 760, 768 Sphincter pupillae, 383 Spinal autonomic neurons, 296 Spinal cord central canal of, 319f organization of, 295–297, 296f, 297f basal ganglia, 298–299, 299f cerebellum, 297–298 cerebral cortex, 298f, 300–301 cerebrum, 298 diencephalon, 298 hippocampal formation, 299–300, 300f Spinal leptomeninges, hyaline plaques of, 333f Spinal nerve roots, anatomy of, 262f Spindle-shaped or myoid cells, 486 Spinnbarkeit test, 1076 Spinous cell layer, Spirochetes, 26 Spitz nevi, Spleen aging differences, 845 anatomy, 838 apoptosis, 837, 837f blood supply, 838 compartments, 836, 836t differential diagnosis, 845–846 ltration function, 840 ow cytometry, 843 functions, 843–845 gross features and weight, 838 hematopoiesis, 845 histologic technique, 846–847, 847f histology, function, and compartments, 836t immunologic function, 845 light microscopy, 838–843 lymphatics, 838 nerves, 838 perifollicular zone, 842–843 prenatal and developmental changes, 836–837 red pulp, 839f, 840–841, 840f red pulp function, 840–841 reservoir function, 845 special procedures, 847 specimen handling, 846 splenectomy, 843 splenitis, 846 splenogonadal fusion, 837f surface and intracellular markers, expression of, 844t ultrastructure, 843 vascular tree, 838–840 white pulp, 839f, 841–842, 841f, 842f white pulp function, 842 Spleniculi, 836 Sponge artifact, 522 Spongiosa, 572, 572f, 573 Spongiosis, Spongiosum, 572 See also Atrioventricular (AV) Spongiotic pericytoma, 192 Spongy bone, 91–92 S-100 protein, 9, 17, 188, 189f, 368, 1191, 1292 in Schwann cells, 273 Sprouty1 (Spry1), 904 Squamocolumnar junction, 613, 1076 Squamous cell, 486 nests, 365 Squamous epithelialization, 1082, 1082f Squamous epithelium, 463 Squamous layers, of epidermis, See also Keratinocytes Squamous metaplasia, 526, 1194 Squamous zone, of anal canal, 719–720, 719f Squiggle cell, 615 Stalk effect, 361 Stapediovestibular joint, of middle ear, 410f Stapedius muscle, 407 Stapes niche, 406 Staphylococcus epidermis, 11 Steatosis, 188 Steiner stain, 23 Stellate cell, 486 Stellate-dendritic cells, Stem cell factor (SCF), 1012 Stensen’s duct, 437, 479 Stent thrombosis, 248 Steroid molecules, 1093 Steroids, 195 Stomach age-related changes, 641 artifacts, 641 blood supply, 634 cardiac and pyloric mucosa, 636–637, 636f differential diagnosis, 641–645, 643f embryology and postnatal development, 633 endocrine cells, 638–639, 638f fundic gland mucosa, 639 gastric function, 640 gross morphologic features, 633–635, 634f histologic features, 635–639, 635f inferolateral margin, 633 lamina propria, 639, 639f lymphatics, 635 metaplasia, 643–645 mucosal zones of, 634f muscular components, 639 nerve supply, 634–635 oxyntic gland mucosa, 637–638, 637f, 638f pancreatic acinar metaplasia, 645 regions of, 633 special procedures and techniques, 641 specimen handling, 645 submucosa, 639 superomedial margin, 633 surface epithelium, 635–636, 636f ultrastructure, 639–640, 640f Stomodeum, 343, 433 Stratum lucidum, Streptococcus pneumoniae, 421 Stress bers, 138 formation of, 138 Striatum, 299 Stroma, 378, 1123–1129, 1196–1198 1327 adipose tissue and skeletal muscle, 1197, 1197f calci cation, 1197–1198 and cornea, 377 endometrial stromal cells, 1127 brous tissue, 1196–1197, 1197f focal lymphocytic thyroiditis, 1196 histology, 1123–1129 hormonal aspects, 1129 luteinized stromal cells, 1123, 1126f lymphocytes, 1196 multifocal sclerosing thyroiditis, 1196 neuroendocrine cells, 1127 psammoma bodies, 1197–1198, 1198f simple chronic thyroiditis, 1196 ultrastructure, 1129 Stromal breakdown, 1098 Stromal cells, 720f in bone marrow, 855–861 (see also Bone marrow) fat cells, 857–858, 857f, 858f macrophages, 858–860, 858f–860f mast cells, 861, 862f nonphagocytic reticular cells, 860, 861f osteoblasts and osteoclasts, 856–857, 856f, 857f Stromal foam cells, 1092f Stromal interaction molecule (STIM1) genes, 1216 Structural organization, of liver, 735–736, 735f, 736f See also Liver Struma ovarii, 1202 Subarachnoid space, 332f Subarticular cysts, 125 Subcortical epithelial cells, 549 Subcutaneous fat, septa and lobules of, 16f Subcutaneous tissue, 16–17 Subcutis See Subcutaneous tissue Subdural hematoma, 332 Subendocardial space, 570 Subepithelial myo broblast (SEM), 684 Sublingual gland, 479 Submandibular gland, 479 Submembranous connective tissue, 508 Submesothelial broblasts, 515 Submesothelial layer, 593–595 histochemistry, 593 immunohistochemistry, 595 interactions of mesothelial and, 595 Submucosa, 617–620, 619f of small intestine, 655–656, 655f (see also Small intestine) of vermiform appendix, 703–704, 704f Submucosal connective tissue, 508 Submucosal lymphoid tissue, 514 Subpleural emphysematous change, in smoking, 518f Subpodocyte exit pores (SEP), 933 Subpodocyte space (SPS), 933 Succinyldehydrogenase, 482 Sucquet–Hoyer canals, 17 Sulcus limitans, 295 Sulcus terminalis, 447 Sulfomucin, 641, 644 Sulfur matrix protein, 40 Super cial dermatophytosis, 20f Super cial vascular plexuses, 17 1328 In d e x Superior pancreatic artery, 779 See also Pancreas Superior vena cava (SVC), 564 Supernumerary glands, 1216 Supraglottic carcinoma, 467 Supraoptic nuclei (SON), 353 Sural nerve, 269, 278 Surface epithelium, of ovary, 1122–1123 histology, 1122–1123, 1122f ultrastructure, 1123 Surfactant protein (SP), 1067 Surgical anal canal, 715 Survivin, 426 Sustentacular cells, 1285 Swiss cheese brain, 338 Swiss-type hypogammaglobulinemia, 542 Sylvius, aqueduct of, 322, 324 Sympathogonia cells, 1234 Synaptic-type vesicles (SSV), 1261 Synaptic vesicle protein 2, (SV2), 1264 Synaptobrevin, 1265 Synaptophysin, 26, 302, 305f, 450, 1264 Synaptosomal-associated protein 23 (SNAP-23), 1216 Syncytial metritis, 1099 Syncytiotrophoblast, 1170 Synovial uid, injury to, 128–129 Synovial membrane, 119–120 injury to, 127–128 T Tail of Spence, 69 Tamm–Horsfall glycoprotein (THGP) antigen, 378 Tamm–Horsfall protein, 938, 944 Tanycytes, 315 Tartrate-resistant acid phosphatase, 96 T-cell, 543 defects, 542 T-cell receptor (TCR), 543, 551 Tegmen tympani, 404 Telangiectasia macularis eruptive perstans, 20 Telogen phase of hair growth, 12 Temporal bone, 402 dissection, 430 pneumatization of, 408 (see also Mastoid air cells) Tendons, 120–121 Teniae coli, 674 Tenon’s capsule, 378, 394 Tensional homeostasis, 138 Tensor tympani muscle, 407 Terminal crest, 568 Terminal duct lobular unit (TDLU), 71, 73 Terminal Schwann cells, 273 Terminals of Perroncito, 281 Testis and excretory duct system, 1004f aging testis, 1013–1014 descent of, 1022 ductuli efferentia, 1015–1016, 1015f ductus (vas) deferens, 1017–1018, 1017f ejaculatory ducts, 1019, 1019f, 1020f epididymis, 1016–1017, 1016f fetal testis, 1010–1013, 1011f–1013f germ cells, 1006–1008, 1006f gubernaculum, 1022, 1022f interstitium, 1008–1009 Leydig cells, 1009–1010, 1009f mesonephric and müllerian remnants, 1020–1022, 1020f–1022f prepubertal, 1010–1013 rete testis, 1014–1015, 1014f scrotal covering, 1003, 1004f seminal vesicles, 1018–1019, 1018f seminiferous tubules, 1004–1005, 1004f Sertoli cells, 1005–1006, 1005f supporting structures, 1003 vascular supply, 1010 Thalassemia major, 455 Thebesian valve, 568 Thebesian veins, 570 Thermogenin, 186 Thick ascending limbs (TAL), 917 Thin limbs of Henle’s loop, 942–943, 942f, 943f Third coronary artery, 572 Thoracic transplantation, 564 Thrombin, 139 Thrombomodulin, 591, 592 Thymic dysplasia, 543 Thymic epithelial cells, 549–550, 549t See also Thymus Thymic hormones, types of, 552 Thymic humoral factor, 552 Thymic hyperplasia, 553–555, 555 Thymic involution, 552–553 Thymic lymphocytes, 550–551, 551f See also Thymus maturation in, 550t Thymidine, 183, 595 Thymocyte, 546, 550 apoptosis, 543 autoreactive, 543 types of, 550 Thymopoietin, 552 Thymulin, 552 Thymus age-related and trophic changes, 552–555 anatomy, 543–544 apoptosis, 543 cell types, 546–548 connective tissue elements of, 548 developmental abnormalities, 542–543 differential diagnosis, artifact and other potential pitfalls, 555–557, 556f embryology, 541–542 epithelial cells, 544–545 epithelial remnants in, 554f function, 552 Hassall’s corpuscles, 545–546, 545f histology, 544–548, 544f immunohistochemistry, 549–551 involution, 552–553 lobular architecture, 544, 544f lymphocytes, 546 medullary epithelial cells, 548, 548f molecular biology, 551–552 myoid cells, 547, 548, 549f neoplasms, 547 neuroendocrine cells, 547 parathyroid gland tissue, 542 pericardium, thymus tissue in, 543 thymic epithelial cells, 549–550, 549t thymic humoral factor, 552 thymic hyperplasia, 553–555 thymic involution, 552–553 thymic lymphocytes, 546, 550–551, 551f thymocytes, 546 thymopoietin, 552 thymosin α 1, 549t, 552 thymulin, 552 thyroid glands, thymic tissue in, 542 tissue of, in ectopic locations, 542 trophic changes, 552–555 ultrastructure, 548, 548f, 549f weight and volume of, 553, 553t Thyroarytenoid muscle, 462 Thyrocytes See Follicular cells Thyroglobulin (TGB), 1185, 1190, 1191 resorption of, 1192 Thyroglossal cyst, 1201 Thyroglossal duct, 489, 1185 Thyroid cartilage, ossi cation of, 462 Thyroid gland abnormal locations, thyroid tissue in, 1200–1202 anterosuperior mediastinal nodes, 1187–1188 blood supply of, 1187 branchial pouch–related structures, 1198–1200 carcinoma, 1190 C cells, 1194–1196, 1194f, 1195f in cervical lymph nodes, 1202 cystic ultimobranchial body remnants, 1198–1199, 1199f Delphian node, 1187 as ectopic tissue, 1198–1200 embryology, 1185–1187, 1186f follicular carcinoma, 1187 follicular cells, 1189–1194, 1189f function of, 1191 gross anatomy, 1187–1188 heterotopic cartilage, 1200 internal jugular chain nodes, 1187 in lateral neck, 1202 lesions of, 1194, 1197 menstrual cycle, 1187 microscopic anatomy, 1188–1189, 1188f, 1189f in midline structures, 1201–1202 mixed follicles, 1198 neuroendocrine cells, 1196 parathyroid gland, 1194, 1198, 1199f parathyroid tissue, 1200 paratracheal node, 1187 pericapsular node, 1187 in pericapsular soft tissues, 1202 prelaryngeal node, 1187 pretracheal node, 1187 pyramidal lobe, 1187 recurrent laryngeal nerve chain nodes, 1187 retroesophageal nodes, 1187 retropharyngeal nodes, 1187 salivary gland–type tissue, 1200 solid ultimobranchial body remnants, 1198 stroma, 1196–1198, 1197f thymic tissue, 1200 thyrocytes, 1189 thyroglobulin, 1185, 1190 In d e x thyroglossal duct cysts, 1185, 1201–1202 thyroid hormone, 1191–1192 thyroid peroxidase, 1191 thyroid transcription factor-1, 1185, 1190 thyrotropin-releasing hormone, 1192, 1196 thyroxine (T4), 1191 triiodothyronine (T3), 1191 Thyroid hormone, 186 Thyroiditis focal lymphocytic, 1196 multifocal sclerosing, 1196 simple chronic, 1196 Thyroid peroxidase, 1191 Thyroid-stimulating hormone (TSH), 363, 1192 Thyroid transcription factor-1 (TTF1), 592, 749, 1185, 1190, 1266 expression, 368 and Napsin, 536f Thyromeres, 1187 Thyrotrope embryonic factor (TEF), 344 Thyrotroph cells, 362–363, 363f Thyrotroph stimulation hormone, 344 Thyrotropin, 1192 Thyrotropin-releasing hormone (TRH), 355, 363, 1192, 1196 Thyroxine (T4), 1191 Tibial tuberosities, 102 Tidemark, 115, 115f Tingible body macrophages (TBM), 822–824 Tissue distribution, of myo broblasts benign and malignant neoplasms, 158–161 Dupuytren’s disease, 148–151 granulation tissue, 142–143, 142f–143f in kidney diseases, 144–147 normal tissues, 141–142 pathologic tissues, 143 quasi-neoplastic proliferative conditions, 147–148, 151–152 responses to injury and repair phenomena, 143–144 stromal response to neoplasia, 152–158 Tissue elastography imaging methods, 139 T-lymphocyte markers, 256 T-lymphocyte recirculation, 242 T lymphocytes, 824 Toker cells, 5, Toluidine blue stains, 16 Tomes’ ber, 434, 451 Tongue, 447–449, 447f, 448f Tono brils, 54 Tono laments, Tonsil, 438–439, 442–443 lingual, 438, 443f, 444f of Luschka, 438 lymphoepithelium, 443f oral, 439 palatine, 438, 471 pharyngeal, 438 tubal, 438 Tonsillar capsule, 471 See also Pharynx Tooth development, 434 Torpedoes, 309 Total parotidectomy, 495 Trabeculae, 100, 838 Trabecular arteries, 838 See also Spleen Trabecular bone, 91–92 Tracheoesophageal stula, 606, 607 Transbronchial biopsies, incidental ndings in, 533, 534f See also Lungs Transforming growth factor β (TGF–β), 364, 903 Transforming growth factor β (TGF–β1), 132, 853 Transglutaminases, 35 Transient receptor potential canonical (TRPC), 1216 Transonychial water loss (TOWL), 40 Transthyretin, 1192 Transurethral resection (TUR), 1000 Traumatic lesions, of peripheral nerve, 282–284 Treg cells, 654 Trephine biopsies, 850 Triangle of Koch, 575 Trichilemmal keratinization, 11 Trichohyalin, 46 Trichohyalin granules, 7, 11 Trichotillomania, 21 Trichrome staining, 515–516 See also Lungs Trigeminal nerve, 301 Trigeminal neurilemmoma, 196 Triglycerides, 182 Triiodothyronine (T3), 1191 Triton tumor, 288 Trochlea, 397, 397f Trocinate, 137 Troma-1, 51 Trophotropism, 1160 Truncal vagotomy, 635 Tubal tonsils, 438 Tubercles See Auricular hillocks Tuberoinfundibular tract, 353 Tubular bones, 86 Tubulin chaperone E (Tbce), 1213 Tubuli rete, 1014 Tubuloalveolar glands, 658 Tubuloalveolar mucous glands, 761 Tumorlets, 368, 523–524, 524f Tumor necrosis factor alpha (TNF-α ), 183 Tumor necrosis factor (TNF), 96, 165, 853 Tumor–node–metastasis (TNM) system, 716 Tumors, of peripheral nervous system, 284–288 Tunica albuginea, 1003, 1036 Tunica vaginalis, 586, 1003 Tunica vasculosa, 1003 Tympanic cavity anterior wall of, 406 oor of, 406 lateral wall, 404 medial wall of, 406 posterior wall of, 406 proper, 407, 407f roof of, 404–405 Tympanic incisure, 402 Tympanosclerosis, 422, 423f Type I collagen, 109 Tyrosinase-related protein-1, 51 Tyrosine, Tyrosine hydroxylase (TH), 1292 Tyson’s glands, 1030 U Ultimobranchial bodies (UBB), 1185 Umbilical cord, 1152–1158 embryology, 1152 1329 gross morphology, 1152–1153, 1152f hematoma of, 1156f histology, 1153 omphalomesenteric duct remnant, 1154f pathologic alterations, 1153–1158, 1155f, 1157f Umbilical hernia, 586 Umbilical vein, 564 Umbilicus and dermal brosis, 19f Umbo, 402 Unipolar neurons, 304f Urachal remnant, 971 Ureter anatomy, 974 embryology, 972 lamina propria, 979–980 microscopic anatomy, 974–975 muscularis propria, 980–983 urothelium variants and benign proliferations, 976–979 Ureteral branching, 904–905 See also Kidney Ureteric branch growth, 906–907 Ureteric bud (UB), 893 formation, 903–904 (see also Kidney) Ureteritis cystica, 977 Urethral and periurethral glands, 1038–1039, 1039f Urethral epithelium, 1039f Urethral ori ce, 1050 Urethra, male distal urethra, 1037–1040 penis, 1028 Urinary bladder anatomy, 972–974, 972f, 973f diverticula, 982 embryology, 971–972 lamina propria, 979–980, 980f microscopic anatomy, 974–975 muscularis propria, 980–983 thickness section of, 983f urothelium, 975–976 urothelium variants and benign proliferations, 976–979 Urothelium, 975–976, 975f ultrastructure of, 976f Urticaria, 20, 21f Urticaria pigmentosa, 16 Uterine serosa, ndings in, 1110t and tubal lymphatics, 1075–1076, 1076f and tubal vasculature, 1075 Uterine natural killer (uNK) cell, 1091 Uterus adult uterus and fallopian tubes, 1073, 1074f anatomy, adult, 1073 anatomy, premenarchal, 1072–1076 apoptosis and the endometrium, 1104 cervical stroma, 1084–1085, 1085f cervix, 1076–1086 embryology, 1071, 1072f endometrial dating, relevance of, 1103–1104 endometrial–myometrial junction, 1104 endometrium, 1086–1104 gross anatomic features of, 1073–1075 indifferent stage, 1071–1072 lymphatics, 1075–1076 1330 In d e x Uterus (continued) myometrium, 1104–1108 natural killer cells, 1091 normal endometrium, histology of, 1088–1103 pregnancy-related changes, 1106–1108 premenarchal uterus and fallopian tubes, 1072–1073, 1073f tissue sampling and associated problems, 1086–1088 uterine and tubal lymphatics, 1075–1076, 1076f uterine and tubal vasculature, 1075 vasculature, 1075 Utricle, 414, 414f, 417–418 See also Ear Uveal tract, 382–386 See also Eyes choroid, 385–386, 386f ciliary body, 383–385, 384f–386f iris, 383, 383f, 384f Uvula, 441–442 See also Mouth salivary gland in, 445f V Vacuoles of Bensley, 1189 Vagal stimulation, 761 Vagal system, 760 Vagina adenosis, 1068–1069 anatomy, 1063–1064 blood supply, 1063 differential diagnosis, 1067–1069 embryology, 1059–1062, 1060f, 1061f epithelial response to hormones, 1065–1066, 1065f epithelium, 1064–1065, 1064f gross features, 1062, 1062f ligaments, 1063 light microscopy, 1064–1066 lymphatic drainage, 1063–1064, 1063f müllerian duct epithelium, remnants of, 1068–1069 nerves, 1063 ultrastructure, 1066–1067 vaginal wall and adventitia, 1066 wolf an ducts, 1067–1068, 1067f Valves of Kerckring, 660 VAMP, 1265 Variceal hemorrhage, 621 Varicella Zoster Virus, 26 Vasa nervorum, 269 Vascular cell adhesion molecule (VCAM), 855 Vascular elements, 1092 Vascular endothelial growth factor A (VEGFA), 936 Vascular endothelial growth factor (VEGF), 913 Vascular endothelium, staining of, 254f Vascular supply bone, 92–93 Vascular surgery, of blood vessels, 247–249, 247t angioplasty, 248 bypass grafts, 248 endarterectomy, 248 prosthetic vessels, 248–249 Vascular theory, 161 Vascular tissues, ultrastructural features of, 250t Vasculature pituitary and sellar region, 347–353 Vasculitis, 17, 17f Vasoactive intestinal peptide (VIP), 360, 622, 766 Vasopressin, 343, 353 Vaterian system, 769 Vaterian system and minor papilla anatomy, 768–770, 768f histology, 770–773, 770f–773f vascular and nerve supply and lymphatic drainage, 770 Vater–Pacini corpuscle, 17f, 18, 1033, 1033f, 1035 VATS lung biopsies, 522 Veins penis, 1040 primary function of, 242 Vellus hair, 19 Velocardiofacial syndrome, 1212 Veno-occlusive disease, 753 Venous drainage, of esophagus, 621 Venous supply, of vulva, 1056 Ventricular assist device (VAD), 564 Ventricularis, 572 See also Atrioventricular (AV) Vermiform appendix acute appendicitis, 705 anatomy, gross, 697–698 appendiceal neuromas, 705–706, 705f, 706f development of, 697–698 dissection and processing techniques, 706–707 functions, 698 histology basement membrane, mucosal, 701 crypt epithelium, mucosal, 700–701 lamina propria, mucosal, 701–703, 701f–703f mucosal architecture, 698–703, 698f–703f muscularis externa, 704 muscularis mucosae, 703 serosa and subserosal region, 703, 704f submucosa, 703–704 surface epithelium, mucosal, 698–699, 698f, 699f lamina propria, 700f, 701–703, 701f–703f mucocele of the appendix, 706 mucosa, 698–703 submucosa, 703–704, 704f surgical perspective, 697–698 Vesicle, 895 Vesicle-associated membrane protein (VAMP), 1216 Vesicular monoamine transporters (VMAT), 1265 Vestibular neuromas, 419 Vestibular papillomatosis, 1050 Vestibulocochlear nerve, 415 Victorian waistband” effect, 581 Video assisted thoracoscopic surgery (VATS), 517 Villi, 649, 1166–1173, 1167f–1169f, 1171f–1173f See also Placenta embryology, 1166–1169 gross morphologic alterations, 1169–1170 gross morphology, 1169 histology, 1170 histopathology, 1170–1173 Villitis of unknown etiology (VUE), 1173 Villous adenoma, 627 Villous edema, 202 Villous epithelium, 650–651, 650f, 651f See also Mucosa Vimentin, 17, 136, 162, 188, 267, 273, 277, 364, 368, 591, 595, 1005, 1010, 1190 Vimentin synthesis, 592 Virchow–Robin space, 329, 335, 819 Visceral pericardium, 565 Visceral pleura, 585, 586f, 587f Visceral pleural tumor, 518 Visinin like (Vsnl1), 907 Vitiligo, 20f Vocalis muscle, 462 Vocal ligament, 462 Volkmann’s canal and bone cortex, 90f Vomeronasal organ, of Jacobson, 455, 456f Von Hippel-Lindau (VHL) disease, 419, 1021, 1279 Von Kossa, 23 Von Willebrand factor, 26, 877 Vulva anatomy, 1046–1056, 1046f, 1047f arterial supply, 1056 cancer, 1045 clinical perspective of, 1045–1046 clitoris, 1051 common complaints, 1045 examination of, 1045–1046 hymen, 1050–1051, 1050f labia majora, 1052–1055, 1053f–1055f labia minora, 1051–1052, 1051f lymphatic drainage, 1055–1056 mons pubis, 1055 nerve supply, 1056 urethral ori ce, 1050 venous supply, 1056 vulvar vestibule, 1047–1050, 1048f, 1049f Vulvar intraepithelial neoplasia (VIN), 1045, 1046 Vulvar vestibule, 1047–1050, 1048f, 1049f See also Vulva Vulvodynia, 1050 Vulvovaginoscopy, 1046 W Wagner–Meissner corpuscle, 287 Waldeyer’s ring, 438, 471 Waldeyer’s sheath, 973 Walthard nest and ovarian hilus, 1125f Walthard nests, 1123 Warthin-Starry stain, 23 Warthin’s tumor, 488, 490, 494 Weber–Christian disease, 195 Weber’s glands, 443 Wedge lung biopsy, 516f Weibel–Palade bodies, 250, 578, 1218 Wernicke’s encephalopathy, 298 Wharton’s duct, 479 Wharton’s jelly, 141, 1022, 1153 In d e x Whipple’s disease, 654, 665 White fat functions, 182–183 gender differences, 182 gross aspects, 184 histology, 184, 184f, 185f lesions adipose tissue within nonfatty lesions, 196 ectopic adipose tissue, 196 hamartomas containing fat cells, 196 intramuscular lipoma, 198–200 lipomas, 196–198, 197f, 198f massive localized lymphedema, 196 mesenchymomas, 196 myxoid change, 198 molecular biology, 182 postnatal development, 182 prenatal development, 180–182, 180f, 181f regulation, 183–184 ultrastructure, 184 White matter, of central nervous system, 301, 302f White pulp, 839f, 841–842, 841f, 842f See also Spleen mantle zone, 841 Wiggling, 401 Wilms tumor, 287, 912 gene, 591 Wilson’s disease, 40, 738, 756 Wirsung, duct of, 768, 770f Wiskott–Aldrich, 726 Wnt gene, 907 Wnt signaling, 94, 652 Wohlfart type B bers, 212 Wolf an duct, 893, 987 vagina, 1067–1068, 1067f Wolff’s law, 85, 87, 117 World Health Organization (WHO), 160, 524, 711 Woven bone, 87–89, 88f Wright-Giemsa See May-Grünwald-Giemsa (MGG) Wright-Giemsa stained bone marrow, hematogone maturation in, 881f WT-1, 591, 591f 1331 X Xanthophyll, 388 Xerostomia, 440 X-linked inhibitor of apoptosis protein (XIAP), 808 X-ray microdiffraction, 39 Z Zenker’s diverticulum, 612 Zenker’s solution, 850 Ziehl–Nielsen stain, 23 Zimmerman’s sign, 390 Zona columnaris, 712 Zona fasciculata, 1239f, 1240, 1240f See also Adrenal gland Zona glomerulosa, 1237f–1239f, 1239–1240 See also Adrenal gland Zona reticularis, 1233, 1239f, 1240–1241 See also Adrenal gland Zonules, 384 Zygotene spermatocytes, 1007 Zymogen granule, 444, 480, 786, 786f ... 40×) 5 92 S E C TIO N VI: Th o x a n d Se ro u s Me m b n e s FIGURE 21 .22 D2-40 immunoreactivity in benign mesothelium is predominantly membranous cells with a high sensitivity (Figure 21 .22 ), but... before histochemical staining is evidence that hyaluronic acid groups are responsible, in large part, for the intensity of staining (21 ) FIGURE 21 .26 The reactive peritoneum shown in Figure 21 .25 ... Cell 19 82; 31(pt 2) :693–703 27 Moll R, Lowe A, Laufer J, et al Cytokeratin 20 in human carcinomas A new histodiagnostic marker detected by monoclonal antibodies Am J Pathol 19 92; 140: 427 –447 28 Moll