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Diffuse pulmonary ossification (DPO) is a rare pulmonary lesion. DPO is typically detected at autopsy rather than premortem. Recently, however, several cases were diagnosed antemortem using computed tomography, high-resolution computed tomography, or video-assisted thoracic surgery. In the present study, we evaluated DPO at autopsy from two patients with post-myocardial infarction (cases 1 and 3) and one patient with duodenal cancer (case 2). Multiple metaplastic bones (nodular in case 1 and 3 or dendriform in case 2) were detected in these three cases. In an attempt to detect aluminum and iron deposition in these metaplastic bones, histochemical investigations were performed. The two nodular types of one and three cases were positive for aluminum and iron, but the dendriform type of case 2 was positive only for aluminum. The depositions occurred in a linear pattern along the calcifying front. It is of great interest that these deposition patterns were similar to those of bones from three previously reported DPO cases and from the bones of hemodialysis patients. It is suggested that these abnormal metal depositions in the calcifying front might disturb the normal mineralization processes of the metaplastic bones, although no morphological abnormality was detected, except for dense black color of calcifying front lines. Further investigations are needed in more patients with DPO to obtain more information on this topic.

KL-6 is known as a useful serum biomarker of the disease activity in interstitial pneumonias. We investigated its usefulness as a biomarker for subtyping intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. IPMNs are generally divided into 4 subtypes, namely pancreatobiliary (PB), intestinal (INT), gastric (GS), and oncocytic (ONC). Aside from the KL-6 antibody, the MUC1, MUC2, MUC5AC, MUC6, and MIB-1 antibodies were also examined. Eighteen IPMN cases were examined, including 12 cases of intraductal papillary mucinous carcinomas (IPMCs) simultaneously associated with dysplasia (IPMDs) and hyperplasia (IPMHs) and 6 IPMD cases with IPMH. KL-6 antibody was positive in the 8 IPMC cases, corresponding to a MUC2-negative PB subtype, but negative in 4 IPMC cases, corresponding to the INT subtype, which is positive for MUC2. IPMD of moderate-to-severe degree positively stained for the KL-6 antibody in the IPMC cases of the PB subtype but not in those of the INT subtype. The IPMH cases were mostly negative for KL-6, similar to the mild IPMD cases. In the 6 cases of mild IPMD and/or IPMH, KL-6 and MUC2 expressions were mostly negative. In conclusion, the KL-6 antibody is immunohistochemically a good biomarker of the PB subtype of IPMC, but not the INT subtype. Identifying IPMN subtypes based on KL-6 stainability would be useful. Clinicopathological studies with more IPMC cases might be needed for further progress in this field of study.

Gastric cancer with the invasive micropapillary carcinoma (IMPC) pattern has been reported to be a variant with poor prognosis and rapid progression. To the best of our knowledge, only 4 cases of gastric cancer from Japan and 11 cases from Korea have been reported to contain the IMPC pattern. In the present study, 4 cases of gastric cancer containing the IMPC pattern from 2 Japanese men and 2 Japanese women are reported. The cancer tissues, including a recurrent lesion in 1 case and lymph node metastases in 2 other cases, were examined immunohistochemically to identify suitable markers for demonstrating the peculiar "inside out" pattern of IMPC and for analyzing HER2 expression. A characteristic IMPC pattern occupied more than 10% of each cancer tissue in these 4 cases. Lymphatic invasions were very often detected; in fact, lymph node metastases were detected in 3 out of 4 cases. The unique "inside out" pattern in IMPC was clearly revealed in all cases by staining with antibodies to both epithelial membrane antigen (EMA) and KL-6, but not with an antibody to CD10. HER2 was positive in 3 of 4 cases with the IMPC pattern, including cases with a recurrent lesion or lymph node metastases. Fluorescence in situ hybridization (FISH) analyses disclosed positive results in case 1, and case 3 including lymph node metastatic foci. Highest FISH titer was 6.8 in case 1, revealing marked amplification of HER-2 gene. Four cases of gastric cancer with the IMPC pattern were reported. EMA and KL-6, but not CD10, were particularly useful markers for visualizing the characteristic "inside out" pattern of the IMPC pattern in stomach cancers, similar to the markers for breast and urinary bladder cancers.

The cAMP-dependent protein kinase inhibitor-β (PKIB) is presumed to be one of the regulatory factors controlling the cAMP-dependent protein kinase A signaling pathway. The aim of this study was to investigate the frequency and patterns of PKIB overexpression in human breast cancer. We also examined the relationship between PKIB and phosphorylated Akt (pAkt) expression in the tumors. Using immunohistochemical techniques, we examined the expression of PKIB, ER, PR, HER2, and pAkt in 148 primary human breast carcinomas. We then analyzed the relationships between PKIB expression and that of pAkt, ER, PR, and HER2, as well as between PKIB expression and various clinicopathological characteristics. We assessed 64 and 27 cases, respectively, as positive for either PKIB or pAkt expression; 20 cases were positive for both PKIB and pAkt. We observed a significant positive correlation between the expression of PKIB and that of pAkt (P = 0.006). We showed by immunohistochemical analyses that PKIB expression was positively correlated with triple-negative breast cancers (P = 0.0004). These findings provide evidence for PKIB overexpression associated with pAkt expression. Furthermore, PKIB expression was strongly correlated with triple-negative breast cancer, suggesting that PKIB expression might contribute to the tumor behavior and development of breast cancer.

It is known that after transurethral resection of the prostate (TUR-P) or a bladder tumor (TUR-BT), necrotizing granuloma formation associated with massive eosinophil accumulation can be detected at the site of the scar, revealing marked eosinophilia. This condition is called post-TUR prostatitis or cystitis. In the present study, we noticed a similar phenomenon in five patients who underwent cholecystectomy, of whom four had gallbladder adenocarcinoma and one had metastatic liver cancer originating from the rectum. We detected necrotizing granulomas with massive eosinophil accumulation, associated with marked eosinophilia. To induce these phenomena, the interval between the first operation (i.e., cholecystectomy) and the second operation (i.e., resection of the hepatic bed and extrahepatic bile duct) is very important. If the interval was 1 week, no granuloma formation was detected. On the other hand, if it was more than 2 weeks, the resected hepatic bed contained necrotizing granulomas with substantial eosinophil accumulation combined with an increase in peripheral eosinophilia (up to 34% in one case). Secondary resection was necessary to induce eosinophilia after cholecystectomy. In this sense, malignancies possessed a relationship with delayed eosinophilia. In the granulomas, some foreign body-type multinucleated giant cells were positive for both anti-interleukin (IL)-5 and CD68 antibodies. In sharp contrast, no eosinophilia was detected after cholecystectomy, with or without hepatic resection consequent to severe adhesion. Clinicians as well as pathologists should keep in mind that these peculiar phenomena of eosinophil accumulation surrounding the necrotizing granulomas and peripheral eosinophilia after cholecystectomy could occur.

According to the current concept of carcinogenesis, neoplastic transformation consists of multistep accumulations of adverse genetic and epigenetic events. p53 is a transcription factor that regulates cellular response to diverse forms of stress through a complex network which monitors genome integrity and cell homeostasis. Mutant p53 loss-of-function, dominant-negative, and gain-of-function properties have been implicated in the development of a wide variety of human cancers, and it is generally accepted that p53 is a component in biochemical pathways central to human carcinogenesis. Study of p53 has come to the forefront of cancer research, and detection of its abnormalities during the development of tumors may have diagnostic, prognostic, and therapeutic implications. In this review, we focus on recent research on overexpression of mutant p53 in human cancer, with an emphasis on mutant p53 regulation, gain of function of mutant p53 in transcriptional effects, and the diagnostic, prognostic, and predictive value of p53 overexpression in human cancer.

Reports of a composite paraganglioma (PG) and ganglioneuroma (GN) in the retroperitoneum are rare. In the present case, dynamic computed tomographic (CT) findings showed a 30 × 22 × 20 mm tumor that was located in the retroperitoneum and which was dissociated from pancreatic tissue and the left adrenal gland. The markedly reddish tumor showed a clear margin and central multicystic changes on the cut surface. The tumor was composed of two major components, the PG and the GN. The paraganglionic cells in the PG component, which were arranged in a nested pattern, occupied the main and central part of the tumor. Both ganglionic cells and Schwann cells in the GN were located in a unorganized pattern in the periphery. The paraganglionic cells exhibited a Zellballen pattern, which consisted of an association of edematous vascular-rich stroma and focal hemorrhage, resulting in multicystic changes. These centrally located tumor cells were pleomorphic in part and did not have mitotic figures. In the periphery, Schwann cells, which were arranged in an obscure and fascicular pattern that was intermingled with large ganglionic cells, were located adjacent to the PG component with a mostly sharp margin. With higher magnification, the border was not as sharp, as revealed especially with chromogranin-A immunostain, in which both the PG and GN components were focally intermingled with each other. The histogenesis of the composite PG and GN was thought to be extraadrenal neural crest cells in the retroperitoneum because the tumor was not located in the adrenal gland or the Zuckerkandl organ, according to the CT findings. The immunohistochemical findings of this rare case of a composite PG and GN in the retroperitoneum are reported with a focus on the peculiar arrangement of these two components.

Characterization of the signet-ring cell carcinoma (sig) component of a urothelial carcinoma (UC) in the urinary bladder of a 64-year-old man, obtained by transurethral resection of bladder tumor (TUR-BT), is reported. In the present case, a characteristic sig component was detected in approximately 20% of UC, G2 tissues. The sig cells were morphologically similar to those found in gastric cancers and were positively stained with periodic acid-Schiff reaction and Alcian blue and mucicarmine stains. Immunohistochemically, the sig cells were selectively positive for carcinoembryonic antigen (CEA), MUC2, and MUC5AC. These immunohistochemical characteristics were similar to those of sig cells in the stomach, except for the positivity with MUC2. It is interesting to note that CAM5.2-positive sig cells were surrounded by CAM5.2-positive UC cells in a solid nest with no apparent associated adenocarcinoma element. In addition, the ultrastructure of sig cells showed multivacuolar cytoplasmic mucin, which proved to be similar to the ultrastructure of gastric cancers. In the present case of UC, G2 was associated with a sig component. Regarding the origin of the sig component in the bladder, it has been suggested that MUC2-positive sig cells in the bladder might be derived directly from metaplasia of UC, without an associated adenocarcinoma component. From this perspective, it may be noteworthy that sig cells in the bladder were selectively positive for MUC2, exhibiting common antigenicity with mucous cells of the gastric intestinal metaplasia. Because UC associated with a sig component carries a worse prognosis than ordinary UC, the presence of the sig component in any UC should be evaluated even within TUR-BT tissues, as in the present case.

Gangliocytic paraganglioma (GPG) is a rare tumor, occurring almost exclusively in the duodenum. In the present case, a submucosal tumor 2.5 x 2 x 1.5 cm in size was located on the anal side of the papilla of Vater, with clear margins and without capsule on cut-surface examination. Tumor cells included three types of cells: ganglion-like cells (GCs), endocrine cells (ECs), and Schwann cells (SCs). The GCs were large with eccentric nuclei with large nucleoli and clear abundant cytoplasm. ECs were detected in small nests, surrounded by bundles of SCs. Immunohistochemically, GCs were positive for synaptophysin, neuron-specific enolase (NSE), and CD56. ECs were positive for chromogranin A, NSE, somatostatin, pancreatic polypeptide, and CD56, and were associated with S100 protein-positive SCs. On fine structural examination, ECs contained numerous membrane-bounded secretory granules, 250-450 nm in diameter, in their cytoplasm, surrounded by a branched, complex basal lamina. SCs possessed basal lamina along their long interlacing cytoplasmic processes. The histogenesis of GPG most likely involves proliferation and differentiation of pluripotent stem cells in the duodenal crypts in the duodenum as a true tumor, although it is also possible that the retroperitoneal components of both GCs and SCs proliferate, together with ECs, from ventral primordial tissue of the pancreas in the duodenum. The immunohistochemical and ultrastructural findings of a case of GPG are reported, focusing on three major cellular components: GCs, ECs, and SCs.

Hyalinizing trabecular tumor (HTT) of the thyroid gland is rare and benign, and it neither recurs nor metastasizes. In this lesion, tumor cells are arranged in trabeculae, in association with hyalinizing mass in the stroma. The origin and nature of the hyalinizing mass are still controversial. We report here a case of HTT with cytological, immunohistochemical, and ultrastructural findings, focused in particular on the hyalinizing mass. Cytologically, tumor cells exhibiting many intranuclear cytoplasmic inclusions and nuclear grooves were found in association with light green-positive, irregular, fluffy membranous structures on touch smear. Staining with antibody to collagen type IV was positive in these membranous structures. Histopathologically, tumor cells exhibited many intranuclear cytoplasmic inclusions, and were positive for staining with antibodies to S100 protein, neuron-specific enolase, thyroglobulin, and vimentin. The hyalinizing eosinophilic mass, which was positive for PAS reaction, and for staining by antibody to collagen type IV, gradually increased in the areas surrounding tumor cells. This mass then appeared to replace the tumor cells, and exhibited a peculiar filiform pattern. We demonstrated ultrastructurally that this pattern was composed of long, irregular, fine cytoplasmic processes of tumor cells and basal lamina-like substance in the hyalinizing mass. In fact, the homogeneous hyalinizing mass, similar to basal lamina-like substance, contained many degenerated cytoplasmic processes at the ultrastructural level. These results suggested that the key cytological finding in differentiating HTT from papillary carcinoma is the fluffy membranous structure, although nuclear pseudoinclusions are important as well. The filiform pattern noted at light microscopic level consisted of long cytoplasmic processes of tumor cells and hyalinized mass at the ultrastructural level.

To evaluate the peculiar "inside-out" pattern in micropapillary (MP) carcinoma, we investigated the usefulness of KL-6 antibody in the assessment of the MP pattern of cancers, in comparison with antibodies to epithelial membrane antigen (EMA), MUC1 (CD227), and CD 10. Immunohistochemical investigation was performed on specimens exhibiting an MP pattern obtained from 12 persons with cancer: 4 with breast carcinoma, 3 with carcinoma of the urinary bladder, and 5 with colonic carcinoma. Immunohistochemical study with KL-6, EMA, and MUC1 antibodies revealed similar continuous linear positive patterns restricted to the surface of the MP pattern in both breast and urinary bladder cancers, revealing the peculiar "inside-out" morphology. However, EMA also gave cytoplasmic positivity in most of the cases tested, and MUC1 was also present in the cytoplasm of some cases. In sharp contrast, immune reactions of colon carcinomas with these antibodies were negative, except for focal positivity for KL-6 and MUC1 antibodies in some cases. CD10 was only focally positive in an MP pattern in 4 of the 5 cases of colon carcinoma and in 1 case with carcinoma of the urinary bladder. These findings suggest that KL-6 is a useful marker to assess the MP character of breast and urinary bladder carcinomas; that MUC1 was similarly positive, with the addition of cytoplasmic positivity in some cases; and that the MP pattern of colon cancer, positive for CD 10, was different in character from both breast and urinary bladder carcinomas, although all these cancers seemingly exhibit similar MP patterns on histopathology. This heterogeneity of the MP pattern in various cancers needs to be investigated when more cases have been accumulated.

A few studies of the morphogenesis of human herpesvirus (HHV) 6 type A and B (HHV-6A, -6B) have been performed using neurogenic, lymphoid, or epithelial cells. When human MT-4 T-lymphotropic virus type I (HTLV-I)-producing lymphoid cells were coinfected with HHV-6B in vitro, viral-specific proteins were clearly detected. We therefore attempted to detect virus particles at the ultrastructural level, focusing on the morphogenesis of such particles. Ultrastructurally, HHV-6B virus particles could be observed in the nuclei, cytoplasm, and extracellular spaces of MT-4 cells, in addition to extracellular HTLV-I particles of C type. In the nuclei, dense-cored or doughnut-shaped viral capsids were found, as well as peculiar tubular rods. When budding to perinuclear spaces, these intranuclear capsids exhibited a thin tegument on their surfaces. Distinct teguments were found in the intracytoplasmic particles, which budded into cytoplasmic vacuoles during the process of maturation. The mature particles were detected in the extracellular spaces and the intracytoplasmic vacuoles, with a distinct tegument and surface spikes. An electron-dense layer in the outer part of the tegument was found in some mature particles located in the extracellular space, but no such layer was detected in mature particles in intracytoplasmic vacuoles. No annulate lamellae, but intranuclear tubular rods, were found in the cytoplasm of MT-4 cells. These observations indicate that HHV-6B in MT-4 cells is similar to HHV-6A in fine structure, but differs from HHV-7 and HHV-8 in ultrastructural characteristics. Further comparisons of HHV-6B with HHV-6A, HHV-7, and HHV-8 are needed with regard to functional activity.

We report a rare case of coexisting pulmonary adenocarcinoma and Langerhans' cell histiocytosis (LCH) in a 78-year-old woman who did not smoke. During follow-up of diabetes mellitus, she had complained of chest pain and was found to have a nodular lesion in S9 of the left lower lobe, which was resected surgically. No abnormal laboratory findings were obtained. Before surgical resection, needle biopsy specimens confirmed the existence of adenocarcinoma. The resected tumor in the left lower lobe was 3.0 x 1.8 x 3.0 cm, and histologically both acinar and bronchioloalveolar cell subtypes of adenocarcinoma were found in cancer foci. In addition to pulmonary adenocarcinoma, Langerhans' cell proliferation associated with marked eosinophil infiltration was incidentally found in a small nodule, approximately 3 x 2 mm in size in the subpleural region. The Langerhans' cells contained interdigitated nuclei, exhibiting rather clear nucleoplasm and cytoplasm; they were positive for S-100 protein, CD1a, and also CD4. Massive eosinophil infiltration was found around the focus of Langerhans' cell proliferation. This nodule appeared to be LCH. The adenocarcinoma and LCH were adjacent, and cancer cells were infiltrated only in the peripheral parts of LCH. The coexistence of adenocarcinoma and LCH appeared to be incidental. The association of adenocarcinoma and LCH is rare, and only several reports of it can be found in the English literature.

A case of urothelial carcinoma (UC) containing a micropapillary carcinoma (MPC) component in the urinary bladder of an 83-year-old man is reported. The MPC component of UC has been reported to be a variant featuring poor prognosis and rapid progression. In the present case, a characteristic MPC component with micropapillary growth, in association with a fine meshwork-like stroma, was observed in less than 10% of fragmented cancer tissues of UC, G3, obtained by transurethral resection of a bladder tumor (TUR-BT). Lymphatic invasion was also detected. UC cancer cells had invaded the prostatic glands and replaced the original epithelial cells. The unique "insideout" feature of the MPC component was immunohistochemically obvious on staining with antibody to epithelial membrane antigen (EMA). On immunohistochemical study, cancer cells of both UC and MPC components were positive for pancytokeratin AE1/AE3 and cytokeratins 7 and 20. Carcinoembryonic antigen (CEA) and CAM5.2 were only focally positive in UC cells. MIB-1(Ki-67) labeling index was high, at 80%-90%, in cancer cells of UC. This was a case of UC, G3 with invasion to the muscularis propria layer of the urinary bladder and also to the prostate. MPC and MPC components in cancers should be recognized as a marker of poor prognosis, even when detected in less than 10% of UC within TUR-BT tissues, as in the present case.

A 73-year-old woman who had undergone resection of urothelial carcinoma (UC) (G3 > G2) of the ureter was also found to have UC (G3) in the urinary bladder, spread throughout the urinary bladder with multiple foci of carcinoma in situ and small papillary cancers. Total cystectomy was therefore performed. On detailed microscopic examination of the extirpated urinary bladder, multiple minute cell nests, 14 in number and less than 2 mm in diameter each, consisting of cells harboring small nuclei and clear cytoplasm, were incidentally detected within the sub-mucosal layer and the proper muscle layer, mainly in the posterior wall of the urinary bladder. Some cell nests were clearly associated with ganglion cells. The cells in minute nests were positive on Grimelius staining and also strongly positive on staining with antibodies to chromogranin A, neuron-specific enolase (NSE), synaptophysin, and vimentin on immunohistochemical staining. In addition, sustentacular cells in the minute cell nests were positive for S100 protein. Staining with antibodies to pancytokeratin AE1/AE3, glial fibrillary acidic protein, and p53 was negative in the cell nests. Based on these findings, the multiple minute foci were diagnosed as paraganglionic cells (PGCs) incidentally detected in the urinary bladder of an elderly woman, in association with UC. Although PGCs are rarely detected in adult human urinary bladder on routine histopathological examination, the possibility of their existence should be kept in mind by pathologists, especially in coexistence with UC. This is the first case of PGCs associated with UC in the human urinary bladder in the English literature.

To clarify the localization of KL-6 and epithelial membrane antigen (EMA) in human lungs, immune reactions to antibodies to these factors were examined in detail at light and electron microscopic levels. Immunohistochemical investigation was performed in 17 cases of usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), hypersensitivity pneumonitis (HP), collagen vascular disease-associated interstitial pneumonias (CVD-IP), viral pneumonia, and bronchobronchioloectasis, as well as in 10 cases of presumably normal pulmonary tissue resected as a result of spontaneous pneumothorax. Immunohistochemical study revealed similar discontinuous linear or dome-shaped positive patterns restricted to type II alveolar cells in presumably normal tissue and only some regions of interstitial pneumonia. In sharp contrast, immune reactions with each of the two antibodies yielded a continuous linear pattern surrounding damaged areas in most regions of interstitial pneumonias and some normal areas as well. Staining for EMA antibody was negative in some regenerating alveolar and bronchial cells in regenerating foci in interstitial pneumonias, although staining for KL-6 antibody was always positive in these cells. Immunoelectron microscopic studies demonstrated similar positive reactions with both antibodies on the surface of alveolar epithelial cells in three of the cases examined, with surface positive granules 100-200 nm in diameter. Thus, although staining for both KL-6 and EMA antibodies exhibited discontinuous positivity restricted to type II alveolar cells in nondamaged regions, immune reactions were continuous and linear in pattern in or around damaged areas of the lungs at both light and electron microscopic levels, probably as a consequence of cell-surface barrier function. These findings in pulmonary tissue might be evidence of defense functions.

Multiple eccrine spiradenomas are rare. In the present study, a detailed investigation of eccrine spiradenoma was performed, focusing in particular on the presence of Langerhans cells (LCs) in the tumor, and their immunohistochemical and ultrastructural characterization. The patient was a woman in her mid-forties who underwent resection of two tumors of the head that were 2.0 and 0.7 cm in size. They were diagnosed as eccrine spiradenoma and were composed of small and large tumor cells with a dense fibrous capsule in the dermis. Immunohistochemically, staining by antibodies to cytokeratins (AE1/AE3, CAM5.2) and CK 5/6 was diffusely positive in all tumor cells, although not in intermingled LCs, which harbored interdigitated nuclei. The cytoplasm of LCs was positive for S-100 protein and CD1a, and their nuclei were also occasionally positive for S-100 protein. Antibody to epithelial membrane antigen was positive for the surface of both intracytoplasmic and true glandular lumina. Fine structural examination revealed the presence of LCs among the tumor cells, extending fine irregular processes among the tumor cells. Birbeck granules were clearly demonstrated in the cytoplasm of LCs. Other fine structural findings included intracytoplasmic lumina with microvilli on their surfaces in some tumor cells. In these examinations of eccrine spiradenoma, LCs, approximately 15/HPF in the tumor, were distinctly detected even at light microscopic level as negative for various types of cytokeratin stains, although they were positive for S-100 protein and CD1a, whereas on ultrastructural examination Birbeck granules were demonstrated in their cytoplasm. Determination of the significance of these LCs in eccrine spiradenoma requires further investigation of a larger number of cases.

The immunohistochemical distribution of SP-D was compared with that of SP-A and KL-6 using a monoclonal antibody in lung tissues of 15 cases of collagen vascular disease-associated interstitial pneumonia (CVD-IP), 4 cases of hypersensitivity pneumonitis (CHP), and 6 cases of other diseases to determine their differences in distribution. In this study, the main targets were alveolar epithelial cells, especially those in the regenerating stage, as well as lymph vessels and stroma. The cytoplasm of type II alveolar epithelial cells and Clara cells was positive for SP-D, with sharp margins; interestingly, however, during the process of regeneration large positive cells were intermingled with relatively small negative cells, even in the same row of cells. In sharp contrast, staining for SP-A and KL-6 was positive in the cytoplasm of all the regenerating alveolar epithelial cells, as well as Clara cells. Staining for KL-6 was usually positive in the surface of air spaces in linear fashion. Staining for SP-A was also positive in elastic fibers in vascular walls. In areas of destruction of pulmonary structures, loose stroma and the endothelial cells of lymph vessels as well as their contents were distinctly positive for SP-A and/or KL-6 but not SP-D. Judging from these results in pulmonary tissues of CVD-IP and HP, SP-D might be a marker for maturity of regenerating epithelial cells. Both SP-A and KL-6 were detected in intimate relationship to the stage of regeneration of alveolar epithelial cells and were expressed before SP-D. In addition, the lymph vessels play a very important role in transfer of KL-6 into the bloodstream.

There is increasing acknowledgment of the public health burden of metabolic syndrome. The metabolic syndrome is defined as emerging cardiovascular risk factors, or atherosclerosis, that are related to underlying insulin resistance. One of the adipokines, adiponectin, has antiatherogenic effects and augments the metabolic effects of insulin. To reduce mortality from cardiovascular disease, it is important to understand the pathophysiological properties of adiponectin and receptors in atherosclerotic regions. Recently, T-cadherin, which has been recognized as a unique cadherin molecule, has been characterized as a novel adiponectin receptor on vascular endothelial cells and smooth muscle. Notably, T-cadherin (also known as CDH13, cadherin 13, and H-cadherin) is abundantly expressed in injured vascular endothelial and smooth muscle cells in atherosclerotic regions. In the present review, we describe recent progress in research on adiponectin receptors, with emphasis on the unique vascular adiponectin receptor, T-cadherin, and its role in vascular disease.

Sclerosing lipogranuloma (SLG) is a rare disease that occurs in the male genital region. We report here three cases of SLG, including two of Y-shaped lesions in the penile base forming an intrascrotal mass, as well as a patient with a mass in the epidydimal region. All three lesions histologically exhibited formation of multiple granulomas consisting of multinucleated giant cells and epithelioid cells, in the fibroadipose tissue or around the epidydimis, in association with eosinophil infiltration. Membranocystic changes were found within the cytoplasm of multinucleated cells. In the two patients with scrotal lesions, membranocystic changes were positive for diastase-PAS reaction and on Sudan black B staining in dewaxed sections. CD68 staining was strongly positive in multinucleated giant cells and epithelioid cells. Most of the lymphocytes infiltrating the lesions were T cells associated with some S-100-positive dendritic cells. T-cell mediated immune reaction appears to be important in the histogenesis of SLG. The histogenesis is generally considered to be a foreign-body reaction to degenerated or damaged fatty tissue or lipids, but no apparent causative factors can be identified in some reported cases. All three patients in the present study had a good clinical course after biopsy or surgical excision. We thus report three cases of SLG including an unusual case in the epidydimal region, with some considerations regarding the histogenesis of SLG.

Post-transurethral resection (TUR) status in the prostate and urinary bladder has been infrequently documented. Furthermore, sequential changes in eosinophil count in peripheral blood (PB) after TUR have not been investigated in detail. In the present study, eosinophil counts and changes in eosinophils in PB were examined before to after TUR of the prostate (P) in 20 patients with benign prostatic hyperplasia. Among them, 14 patients exhibited increased numbers of eosinophils, the greatest increase being 17%. After TUR to treat bladder tumor (BT), massive infiltration of eosinophils into the resected areas, peaking 1 month later, was also detected in 8 of 15 cases of post-TUR cystitis. The PB eosinophil counts increased by more than 5% in two of five cases of post-TUR cystitis in which eosinophil counts were obtained before and after surgery. Most infiltrating eosinophils reacted positively to antibodies to eosinophil cationic proteins. These results indicated that, in patients with post-TUR prostatitis, the number of eosinophils in PB increased, and peaked 1 month later, with infiltration by eosinophils observed. Pathologists and urologists should be aware of the potential for increase in eosinophils not only in regions of TUR but also in PB.

To investigate the fine-structural nature of nuclear inclusions immunopositive for surfactant protein A (SP-A) antibody staining, a detailed ultrastructural study was performed, as well as immunohistochemical examination of pulmonary adenocarcinomas. Surgically resected tumor specimens from 31 patients were examined by immunohistochemistry focused on reactivity to SP-A and thyroid transcription factor 1 (TTF-1) antibodies. Only cases with >5% positive nuclear inclusions in cancer cells were considered positive, some of which were examined by electron microscopy. Immunohistochemically, 6 of 31 cases were doubly positive for SP-A and TTF-1 antibodies. On electron microscopy, SP-A-positive nuclei contained diffuse or globular fine granular substance as inclusions. Both types of globular and diffuse inclusions were sometimes connected to the inner nuclear membrane, in association with fragmented or stacked membranous structures. The findings of this study suggested that nuclear inclusions positive for SP-A antibody staining in adenocarcinomas of the lung were derived from accumulated content in the perinuclear cistern resembling pseudoinclusion processes and composed of proteins antigenically cross-reactive with SP-A.

p53 has been called the "cellular gatekeeper" and the "genome guard," because in response to exposure to DNA-damaging agents, it induces cell-cycle arrest in G1 or apoptosis and also directly affects DNA replication. Multiple mechanisms regulate p53 activity and posttranslational modification, including multisite phosphorylation of wild-type p53, in particular. Normal functions of wild-type p53 are abrogated by mutation of this gene, and oncogenic studies have revealed that p53 mutation is among the most common genetic alteration in human cancers. It is generally accepted that mutant p53 protein may not only lose the tumor suppressor functions of wild-type p53 but also acquire additional tumorigenetic roles, including dominant-negative effects and gain of function. Although many studies have revealed such aberrant functions of mutant p53, less is known about the posttranslational phosphorylation status of mutant p53 and novel biological functions of phosphorylation in carcinogenesis.