Alpha-1-antitrypsin deficiency (Siiyama) as indication for lung transplantation: proper timing for surgical intervention.

The authors report a new familial case of alpha-1- antitrypsin (AAT) deficiency with severe pulmonary emphysema and hemoptysis. A severely reduced serum AAT level of the proband, a 56-year-old farmer's wife and her sister were observed. Mutation analysis of the AAT gene was performed using allele-specific polymerase chain reaction (PCR) analysis followed by direct sequencing. The proband and her younger sister proved to be homozygous for PISiiyama. Although home oxygen therapy was induced in addition to previous medications including bronchodilators and cardiovascular conditioning, the proband's rate of decline of forced expiratory volume at one second (FEV1) was progressing. Lung transplantation was therefore advisable for the patient. Clinical analysis on Japanese cases reported in the literature shows that the rate of decline of FEV1 is one of the most convenient prognostic factors to find proper timing for surgical intervention. Lung transplantation is one of the best reliable current therapies to improve quality of life of severely impaired patients.

Pulmonary adenocarcinoma with micropapillary component: an immunohistochemical study. Case report.

Micropapillary carcinoma has been described in various organs, including the breast, urinary bladder, ovary and lung. We here present a case of pulmonary micropapillary carcinoma in a 72-year-old Japanese man who died of respiratory failure and septic shock, following which autopsy was performed. A mass measuring 2.5 x 2.5 x 2.5 cm was observed in the left lower lobe of the lung. The tumor showed moderately differentiated papillary adenocarcinoma with a focal micropapillary component. Carcinomatous lymphangiosis was also observed in the left lung and metastatic lesions were observed in the bilateral lung, liver, vertebra, muscle layer of the urinary bladder, right adrenal gland, spleen and lymph nodes. The micropapillary component was predominant at some metastatic sites. Immunohistochemically, both the adenocarcinoma and micropapillary components were positive for cytokeratin (CK) 7, CK19, TTF (thyroid transcription factor)-1, carcinoembryonic antigen (CEA) and surfactant apoprotein A (SP-A), and negative for CK20, estrogen receptor, progesterone receptor, uroplakin III, and CA125. The invasive area of the conventional adenocarcinoma component contained a large number of myofibroblasts, whereas the stroma of the micropapillary component contained a small number of myofibroblasts. However, no myofibroblasts were observed in the stroma of the central core of the non-invasive micropapillary carcinoma. Several lymphatic invasions by neoplastic cells were identified in the peripheral area of the micropapillary component using D2-40 antibody. The immunohistochemical profile may be helpful in determining the primary location of the neoplasm containing micropapillary features. Myofibroblasts are present in the stroma of the invasive neoplastic nests in the micropapillary component as well as the conventional adenocarcinoma component, and D2-40 monoclonal antibody may be useful for evaluating the lymphatic invasion of pulmonary micropapillary carcinoma.

Review of mucinous tubular and spindle-cell carcinoma of the kidney with a focus on clinical and pathobiological aspects.

Recently, the characterization of mucinous tubular and spindle-cell carcinoma (MTSCC) has been established. MTSCC predominantly occurs in females. This tumor is histologically characterized by eosinophilic cytoplasm, elongated and anastomosing tubules, myxomatous stroma and low-grade nuclear cytology. Proliferation of spindle cells or foci of clear cells are also observed. Histochemically, the myxomatous stroma exhibits a positive reaction for alcian blue and colloidal iron stainings. Ultrastructurally, short microvilli are focally observed and junctional complexes are present. Recently, multiple losses of chromosomes 1, 4, 6, 8, 9, 13, 14, 15 and 22 in MTSCC have been elucidated by using comparative genomic hybridization. The prognosis of MTSCC is generally favorable, but some cases may show local recurrence or metastasis. Some cases with MTSCC seem to show overlapping histology with low-grade collecting-duct carcinoma. Therefore, further investigation will be needed to elucidate pathobiological characteristics of MTSCC.

The distribution of CD34-positive stromal cells and myofibroblasts in colorectal carcinoid tumors.

In order to understand the stromal reaction associated with colorectal neoplasms, we examined specimens from 26 patients including normal colorectal tissues (n=15), carcinoid tumors (n=12), well differentiated adenocarcinomas (n=10), and poorly differentiated adenocarcinomas (n=4), using an immunohistochemical method. Myofibroblasts and CD34-positive stromal cells were distributed in the mucosa and in the area between the submucosal and subserosal layers, respectively. However, the distribution of these cells markedly changed with the invasion of neoplasms. Namely, myofibroblasts were abundant in the invasive stroma of all colorectal neoplasms. CD34-positive stromal cells were completely absent from the invasive stroma of colorectal cancers. On the other hand, CD34-positive stromal cells were absent from four out of five carcinoid tumor cases with lesions measuring less than 2 mm in size, but were present in all seven cases of carcinoid tumors measuring more than 2 mm. Double-immunostaining identified stromal cells expressing both ASMA and CD34 in several carcinoid tumor cases. Finally, no CD34-positive stromal cells were observed in the invasive stroma of colorectal cancers. However, the distribution of these cells in carcinoid tumors may depend on the lesion size. Namely, CD34-positive stromal cells existed between neoplastic nests in large-sized carcinoid tumors. Myofibroblasts in the stroma of colorectal neoplasms may originate from CD34-positive stromal cells.

The appearance of myofibroblasts and the disappearance of CD34-positive stromal cells in the area adjacent to xanthogranulomatous foci of chronic cholecystitis.

We investigated the distribution of myofibroblasts and CD34-positive stromal cells in normal gallbladder and its pathological conditions (cholecystitis, n=25) using immunohistochemistry and in situ hybridization. In the wall of normal gallbladder, myofibroblasts were generally absent from all layers, but many CD34-positive stromal cells were observed in the connective tissue layer. In chronic cholecystitis with mild perimuscular fibrosis, a small to moderate number of myofibroblasts appeared in the mucosal layer. In chronic cholecystitis with marked perimuscular fibrosis, a small to large number of myofibroblasts appeared predominantly in the connective tissue layer, whereas the number of CD34-positive stromal cells decreased at the same location, although the number of myofibroblasts increased. In chronic cholecystitis with xanthogranulomatous foci, a small to large number of myofibroblasts were observed in the periphery of the xanthogranulomatous reaction and adjacent area. In contrast, CD34-positive stromal cells were completely absent or were limited to the area just around the xanthogranulomatous reaction. Induction of collagen type I and III mRNA was predominantly observed in the cytoplasm of myofibroblasts associated with the marked fibrosis, which consisted primarily of mature collagen fibers, and in the cytoplasm of myofibroblasts around the xanthogranulomatous reaction, respectively. Finally, myofibroblasts were observed in all subtypes. The increased number of myofibroblasts was most prominent in the connective tissue layer of chronic cholecystitis with marked perimuscular fibrosis or in the area adjacent to xanthogranulomatous foci of chronic cholecystitis. Under these conditions, CD34-positive stromal cells tended to disappear from the connective tissue layer, which exhibited an increase in myofibroblasts.

Consistent lack of CD34-positive stromal cells in the stroma of malignant breast lesions.

To examine the distribution of CD34-positive and ASMA-positive stromal cells in various breast lesions, we performed immunohistochemical assays (using a streptavidin-biotin immunoperoxidase technique) of tissue specimens, obtained by excisional biopsy and partial or total mastectomy, from 62 patients with breast lesions. Specimens were obtained from 64 lesions as follows: fibrocystic disease (n=12), intraductal papilloma (n=4), fibroadenoma (n=17), invasive lobular carcinoma (n=6), invasive ductal carcinoma (n=20) and invasive micropapillary carcinoma (n=5). In normal breast tissue (controls), CD34-positive spindle cells were abundant in the intralobular stroma, but no ASMA-positive stromal cells were identified except myoepithelial cells. Small to large numbers of CD34-positive cells were observed in the stroma of 29 of 33 benign diseases. In all invasive carcinomas (lobular, ductal and micropapillary), no CD34-positive stromal cells were observed in the stroma. In the stroma of benign lesions, the number of ASMA-positive stromal cells was various, but the stroma of all invasive breast cancers contained ASMA-positive stromal cells. The present results indicate that disappearance of CD34-positive stromal cells consistently occurs in the stroma of invasive carcinoma of the breast, irrespective of histological type and may be associated with the presence of ASMA-positive stromal cells.

The participation of myofibroblasts in the capsular formation of human conventional and chromophobe renal cell carcinomas.

The presence of myofibroblasts has been elucidated in neoplastic capsules of various organs. In the present article, we examine the presence of myofibroblasts in the capsule of renal cell carcinoma (RCC) and discuss the origin of the myofibroblasts. Nineteen renal tumors (conventional RCC, n=17; chromophobe RCC, n=2) with evident and totally surrounded fibrous capsule were selected. Abundant myofibroblasts were immunohistochemically observed in the capsule of the RCCs. These findings were confirmed by electron and immunoelectron microscopic studies of three conventional RCCs. Type III and I collagens were predominant in the outer and inner layers of the RCC capsule, respectively. The cytoplasm of the tubular epithelial cells in the tissue surrounding the neoplastic capsule stained positively for transforming growth factor (TGF)-beta 1. In situ hybridization detected type I collagen mRNA in myofibroblasts of the capsule. Myofibroblasts may participate in the capsular formation of conventional and chromophobe RCCs through the collagen production.

Skeletal muscle blood flow, metabolism and morphology in chronic congestive heart failure and effects of short- and long-term angiotensin-converting enzyme inhibition.

Blood flow to skeletal muscle during exercise is limited in patients with chronic congestive heart failure compared with normal persons. This may, in part, be attributed to the inability of the vessels to dilate adequately. In addition, an abnormal skeletal muscle metabolism with oxidative capacity can be demonstrated in patients with chronic congestive heart failure. The latter may partially explain why vasodilators and inotropes that improve central hemodynamics, global leg perfusion or skeletal muscle blood flow during exercise do not increase oxygen uptake by working muscle after acute drug administration. Furthermore, increases in blood flow to skeletal muscle may be redistributed to inactive or less oxygen-dependent muscle fibers. Although acute angiotensin-converting enzyme inhibition usually neither exerts substantial improvement in exercise hemodynamics nor interferes with leg perfusion during exercise, skeletal muscle blood flow and oxygen uptake gradually increases with long-term angiotensin-converting enzyme therapy, leading to improved systemic oxygen consumption and exercise tolerance. Several factors, such as reduction in plasma and vascular angiotensin II and sympathetic nervous activity, increased prostaglandin levels and renal function may contribute to this beneficial long-term effect.

Expression of CD9/motility-related protein 1 (MRP-1) in renal parenchymal neoplasms: consistent expression in papillary and chromophobe renal cell carcinomas.

CD9 is a glycoprotein that is abundant in hematopoietic cells. Recently, it has been reported that CD9 is also present in the human kidney. In this article, we investigated the expression of CD9 using an immunohistochemical technique. We also studied the expression of CD9 protein and messenger RNA (mRNA) in tissue samples of some renal tumors using immunoblotting and reverse-transcription polymerase chain reaction (RT-PCR) analysis. Immunohistochemically, all tumors of papillary and chromophobe renal cell carcinomas (RCCs) and oncocytomas expressed CD9. In addition, CD9 was expressed in 31 of 66 conventional RCCs and 1 of 4 collecting duct carcinomas. On immunoelectron microscopy, CD9 was identified on the plasma membrane of a conventional RCC. The presence of CD9 protein in normal kidneys and various renal tumors, except for a collecting duct carcinoma and an oncocytoma, was confirmed by immunoblotting. On RT-PCR analysis, the expression of CD9 mRNA was observed in 1 normal kidney, 2 conventional RCCs, and 1 oncocytoma. The frequency of immunohistochemical CD9 positivity was significantly higher in papillary and chromophobe RCCs than in collecting duct carcinomas and conventional RCCs, respectively. These results suggest that CD9 may be a beneficial marker in the differential diagnosis between papillary RCCs and collecting duct carcinomas and also between chromophobe and conventional RCCs.

Inhibition of in vitro fertilization by a monoclonal antibody reacting with the zona pellucida of the oviductal egg but not with that of the ovarian egg of the golden hamster.

A glycoprotein designated ZP-0 is secreted from the epithelial cells of the oviduct and is bound to the zonae pellucidae (ZPe) of the oviductal eggs. We have previously established a monoclonal antibody reacting with ZP-0, termed AZPO-8. In the present study, we have examined the effect of AZPO-8 on in vitro fertilization in the hamster. Treatment of the oviductal eggs with AZPO-8 at concentrations of more than 100 micrograms/ml resulted in: (1) the formation of "zona precipitation" on the outer region of the ZP; (2) inhibition of sperm binding to ZP; (3) the acquisition of resistance to protease treatment. Fertilization was inhibited by AZPO-8 in a dose-dependent manner. These results indicate that a monoclonal antibody (MoAb) to an additional component of ZP derived from the oviduct shows an inhibitory effect on fertilization in vitro.

A monoclonal antibody reacting with the zona pellucida of the oviductal egg but not with that of the ovarian egg of the golden hamster.

A monoclonal antibody (mAb) designated AZPO-8 was produced by hybridizing a mouse myeloma with spleen cells from BALB/c mice immunized with materials obtained from the hamster oviduct. With an immunofluorescence test, AZPO-8 reacted with the zona pellucida (ZP) of ovulated eggs in the oviduct (ZP-OVI) but not with the zona pellucida of eggs in the ovary (ZP-OVA). Using indirect enzyme immunostaining, this mAb reacted with epithelial cells of the oviduct, the uterus (especially the cervical epithelium) and the gastric mucosa, but not with other hamster tissues examined. The reactivity of antigen-positive tissues was abrogated by pretreatment of the tissues with periodic acid. Western blotting analysis revealed that AZPO-8 reacted with substances of broad molecular weight range, and the strongest reactivity was detected at a molecular weight of approximately 200,000 in both cases when extract of ZP-OVI or the hamster oviduct was applied on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) gel. AZPO-8 showed strong hemagglutination activity only to group A human red blood cells. These results indicated that (1) ZP-OVI had an antigen that was not detected on ZP-OVA, (2) ZP-OVI and the oviduct shared the same antigenicity, and (3) the antigenic determinant reactive with the mAb might be carbohydrate in nature. A possible role of this antigen in fertilization was discussed.

Review of papillary renal cell carcinoma with focus on clinical and pathobiological aspects.

Recent studies have shown that papillary renal cell carcinoma (RCC) is clinically and genotypically a distinct entity. Papillary RCCs account for about 10-15% of renal parenchymal neoplasms. Macroscopically, the cut surface is yellow or brown in color and large tumors frequently show cystic change. Hemorrhage and necrosis are common. Histologically, Delahunt and Eble have classified papillary RCCs into type 1 (small cells, single layer) and type 2 (large cells, pseudostratification) according to the cytoplasmic volume and thickness of the lining cells. In chromosomal analysis, gain of chromosomes 7 and 17, loss of Y chromosome and additional gains (chromosome 3q, 8p, 12q, 16q and 20q) are frequently found in type 1 papillary RCCs, but the chromosomal aberration of type 2 papillary RCCs seems to be more heterogenous than that of type 1 papillary RCCs. Mutations of MET proto-oncogenes in some cases of both hereditary and sporadic papillary RCCs have recently been detected. Furthermore, all hereditary and sporadic papillary RCCs with MET proto-oncogene show type 1 histological features. Type 1 papillary RCCs generally seem to have a favorable prognosis, but type 2 tumors have a worse prognosis than do type 1 tumors. Papillary RCCs with involvement of the X chromosome and cancer syndrome with predisposition to cutaneous/uterine leiomyomas and papillary RCCs, the histological features of which are basically different from those of usual papillary RCCs, have also been recently reported. Since papillary RCCs seem to constitute clinically, histologically, and even genetically more heterogenous groups than previously thought, further investigations are needed to characterize the subtype of papillary RCC.

Review of sarcomatoid renal cell carcinoma with focus on clinical and pathobiological aspects.

In sarcomatoid renal cell carcinoma (RCC), it is generally accepted that the sarcomatoid portion is derived from metaplastic transformation of carcinoma. Sarcomatoid RCCs account for about 1-8% of all renal tumors. Macroscopically, tumors generally form encapsulated masses and show invasive growth. Sarcomatoid RCCs originate from all subtypes of RCCs, including conventional, papillary, chromophobe, and collecting duct carcinomas. With regard to the growth pattern of the sarcomatoid component, malignant fibrous histiocytomatous, fibrosarcomatous and unclassified sarcomatous patterns are frequently seen. Immunohistochemically, sarcomatoid RCCs are generally positive for AE1/AE3, epithelial membrane antigen (EMA) and vimentin and negative for desmin, actin and S-100. Little is know about genetic alterations in sarcomatoid RCCs. Further studies are therefore needed to identify the key gene involved in sarcomatoid transformation of RCCs.

Review of collecting duct carcinoma with focus on clinical and pathobiological aspects.

In recent years, the concept of collecting duct carcinoma (CDC) has been established. CDCs constitute about 0.4 to 2% of RCCs. Macroscopically, CDCs occur in the renal medulla. On the cut surface, they are generally firm, white or grey and poorly circumscribed. Histologically, CDCs are characterized by various cytological and histological appearances. Furthermore, desmoplastic stromal reaction around the tumor and atypical hyperplastic changes or carcinoma in situ in the adjacent medullary collecting duct are frequently observed. Histological distinction from papillary RCCs is most important, because both tumors share some structural and histochemical features, and it seems that some investigators have confused diagnostic criteria for CDCs. On the other hand, the concept of medullary carcinoma, which preferentially occurs in a black race and shows histological features similar to those of CDC, has also recently been established. Although there have been few studies on chromosomal abnormalities of CDCs and consistent abnormalities have not been identified, a recent study using microsatellite analysis has shown a high frequency (60%) of LOH in 1q32.1-32.2. Further studies are needed to elucidate the genetic characteristics of CDCs and to determine the relationship or difference between CDCs and medullary carcinomas.

Review of chromophobe renal cell carcinoma with focus on clinical and pathobiological aspects.

In recent years, the concept of chromophobe renal cell carcinoma (RCC) has been established. Chromophobe RCCs account for about 4-6% of all renal tumors. Macroscopically, the cut surface of the tumor is generally grey-beige in color. Histologically, there are two variants (typical and eosinophilic). In the typical variant, large tumor cells with architecture of a compact tubulo-cystic pattern proliferate. The cytoplasm is abundant and shows a fine reticular translucent pattern. The cell border is thick, prominent and eosinophilic. In the eosinophilic variant, tumor cells are smaller and markedly eosinophilic, and a perinuclear halo is often seen. Histochemically, the tumor cells generally show a diffuse and strong reaction for Hale's colloidal iron staining. Ultrastructurally, tumor cells contain many cytoplasmic microvesicles (150-300 nm). In chromosomal analysis, a low chromosome number is characteristic of chromophobe RCCs, due to the frequent occurrence of a combined loss of chromosomes 1, 2, 6, 10, 13, 17, and 21. In differential diagnosis, histological distinction from oncocytomas, which share a common phenotype (intercalated cells of the collecting duct system), is most important. In this diagnostic setting, recent studies have given rise to several problems. Firstly, some cases of coexistent chromophobe RCC and oncocytoma (so-called renal oncocytosis) or cases of oncocytoma with metastasis have recently been reported. Secondly, the existence of chromophobe adenoma, which is the benign counterpart of chromophobe RCC, and an oncocytic variant of chromophobe RCC has recently been suggested. Therefore, further studies are needed to elucidate the relationship between chromophobe RCCs and oncocytomas, to confirm whether chromophobe adenoma actually exists or not, and to identify the key gene that causes chromophobe RCCs.

Review of metanephric adenoma of the kidney with focus on clinical and pathobiological aspects.

The concept of metanephric adenoma has become established in recent years. Metanephric adenoma is a rare neoplasm. Macroscopically, the cut surface of the tumor displays a tan to gray or yellow color, and tumors generally form well-circumscribed masses. Histologically, tumors are composed of small epithelial cells that form small acini. Glomeruloid bodies, which are composed of lobulated papillary projections, are occasionally seen. Although there have been few studies using chromosomal analysis, two recent studies have shown partial monosomy or LOH of 2p. On the other hand, the concept of metanephric tumors has recently become broadened. These tumors include metanephric adenomas, adenofibromas and stromal tumors, and they compose a continuous histological spectrum. Therefore, further studies on various aspects are needed to identify the gene responsible for the occurrence of metanephric tumors and, furthermore, to clarify the association among the three types of metanephric tumors.

Review of renal oncocytoma with focus on clinical and pathobiological aspects.

Renal oncocytomas account for about 3-7% of all renal tumors. Macroscopically, the cut surface of the tumor is generally mahogany brown or dark red in color. A central scar is occasionally observed. Histologically, tumor cells with finely granular cytoplasm proliferate in an edematous, myxomatous or hyalinized stroma with a nested, tubulocystic, solid or trabecular pattern. Ultrastructurally, tumor cells contain many mitochondria with lamellar cristae. Mitochondrial DNA alterations are consistently observed in renal oncocytomas. In chromosomal analysis, renal oncocytomas comprise a heterogenous group. Combined loss of chromosomes Y and 1, rearrangements affecting band 11q12-13, involvement of 12q12-13, loss of 14q, and the lack of combination of LOH at specific chromosomal sites have been reported. In differential diagnosis, the histological separation from chromophobe RCCs is of great importance. In such a setting, ultrastructural or chromosomal analysis is very useful. However, there are several findings suggesting a close relationship between chromophobe RCC and oncocytoma. First, both tumors share a phenotype of intercalated cells of the collecting duct system and mitochondrial DNA alterations. Second, some cases of coexistent oncocytoma and chromophobe RCC, designated as "renal oncocytosis", have recently been reported. Third, oncocytic variants of chromophobe RCCs that have similar ultrastructural features to those of oncocytomas have been reported. Fourth, the existence of chromophobe adenoma, which is the benign counterpart of chromophobe RCC and shows loss of chromosomes Y and 1, has recently been suggested. Finally, although almost all oncocytomas behave in a benign fashion, some cases of oncocytoma that caused metastasis or resulted in death have also been reported. Therefore, further studies are needed to resolve these problems and also to elucidate the genetic mechanisms responsible for the occurrence of oncocytomas.

Immunohistochemical identification of intracytoplasmic lumens by cytokeratin typing may differentiate renal oncocytomas from chromophobe renal cell carcinomas.

Renal oncocytomas and chromophobe renal cell carcinomas (RCCs) share a common phenotype and both originate from the intercalated cells of the collecting duct. This makes it very difficult to differentiate between the two tumors immunohistochemically. Therefore, we studied the results of immunohistochemistry focusing on certain characteristic structures that are occasionally present in renal oncocytomas. We carried out Hale's colloidal iron staining and immunohistochemistry for various cytokeratins (cytokeratins 7, 8, 10, 10/13, 14, 18, 19 and 20, and AE1/AE3) in four oncocytomas and six chromophobe RCCs. In addition, one renal oncocytoma and one chromophobe RCC were studied using electron microscopy. Two renal oncocytomas and one chromophobe RCC were completely unstained by colloidal iron. There was no evident difference between the immunohistochemical characteristics of oncocytomas and those of chromophobe RCCs. However, in all four renal oncocytomas we identified intracytoplasmic ring-like positive reactions for some cytokeratins (at least 3 antigens of cytokeratins 7, 8 and 19, and AE1/AE3), which corresponded ultrastructurally to the intracytoplasmic lumens (ICLs). In contrast, no such structures were found in any of the chromophobe RCCs using the antibodies employed. Therefore, immunohistochemical identification of ICLs by cytokeratin typing may be useful for differentiating between renal oncocytomas and chromophobe RCCs and be more sensitive in this respect than colloidal iron staining.

The distribution and role of myofibroblasts and CD34-positive stromal cells in normal pancreas and various pancreatic lesions.

To elucidate the distribution and role of myofibroblasts and CD34-positive stromal cells in various pancreatic lesions, we performed an immunohistochemical study using a streptoavidin-biotin immunoperoxidase technique. We selected 43 pancreatic lesions from 1 biopsied, 22 surgically resected and 12 autopsied specimens: acute pancreatitis (n=3), chronic non-obstructive pancreatitis (n=4), obstructive pancreatitis (n=7), islet cell tumor (n=4), serous cystadenoma (n=7), mucinous cystadenoma (n=6), and invasive ductal carcinoma (n=12). In normal pancreas, myofibroblasts and CD34-positive stromal cells were predominantly present in the peridcutal and periacinar areas, respectively. Both myofibroblasts and CD34-positive cells were observed in the stroma of chronic pancreatitis. In four islet cell tumors, myofibroblasts were present in the stroma of the tumor center, but no CD34-positive stromal cells were identified. Additionally, myofibroblasts and CD34-positive stromal cells were located in the inner layer and the outer layer of the capsule of three islet cell tumors, respectively. In nine of the thirteen cystadenomas, only myofibroblasts were recognized in the cyst wall. In the remaining four cystadenomas, a small number of CD34-positive cells were observed in the cyst wall. In 12 invasive ductal carcinomas, the stroma possessed a lot of myofibroblasts, but there were no or few CD34-positive stromal cells. In conclusion, it seems that the abundant amount of CD34-stromal cells in the main lesions is characteristic of chronic inflammatory lesions. Myofibroblasts and CD34-positive stromal cells may play a role in regulating the tumor growth in the capsule of islet cell tumors of the pancreas.

The disappearance of CD34-positive and alpha-smooth muscle actin-positive stromal cells associated with human intra-uterine and tubal pregnancies.

In order to elucidate the change in alpha-smooth muscle actin (ASMA)-positive and CD34-positive stromal cells associated with pregnancy, we examined endometrial and Fallopian tube tissues from 40 patients including normal endometrium (n=10), intra-uterine pregnancy (n=10), normal Fallopian tube (n=10), and tubal pregnancy (n=10), using immunohistochemistry. In normal endometrium, only a few ASMA-positive cells were focally observed. Additionally, a wide range of CD34-positive stromal cell abundance was observed. In normal Fallopian tube mucosa, a small to moderate number of both ASMA-positive and CD34-positive stromal cells was observed. Neither ASMA-positive nor CD34-positive stromal cells were observed anywhere in the decidual stroma during both intra-uterine and tubal pregnancies. Likewise, a varying abundance of ASMA-positive cells but no CD34-positive stromal cells were observed at the fetal side during both intra-uterine and tubal pregnancies. In conclusion, the disappearance of CD34-positive and ASMA-positive stromal cells may be an indicator of decidualisation induced change in the stroma during both intra-uterine and tubal pregnancies. ASMA-positive stromal cells at the fetal side associated with pregnancy may play a role in the production of villous extracellular matrix or regulation of blood flow.