Flat adenoma-carcinoma sequence with high-malignancy potential as demonstrated by CD10 and beta-catenin expression: a different pathway from the polypoid adenoma-carcinoma sequence.

AIMS: CD10+ colorectal carcinomas have a high risk of giving rise to liver metastasis. The aim was to examine phenotypic expression in colorectal neoplasia and to elucidate changes in such expression through the adenoma-carcinoma sequence. METHODS AND RESULTS: We examined the expression of various proteins immunohistochemically in 111 flat [non-polypoid growth (NPG)] colorectal neoplasms, categorized into 28 low-grade (NPG-LGN), 44 high-grades (NPG-HGN) and 39 cases of invasive neoplasia (NPG-IN), as well as in 96 polypoid [polypoid growth (PG)] neoplasms, categorized into 26 PG-LGN, 39 PG-HGN and 31 PG-IN according to the Vienna classification. CD10 was more frequently expressed in NPG than in PG neoplasia. MUC2 and MUC5AC were more frequently expressed in PG than in NPG neoplasias. Nuclear beta-catenin was more frequently expressed in NPG-LGN than in PG-LGN. No difference in p53 expression was found between NPG and PG neoplasia. CONCLUSIONS: From the viewpoint of the expression of CD10 and beta-catenin, it would appear that NPG-LGN differs significantly from PG-LGN, thereby indicating that NPG-LGN is a precursor of CD10+ carcinoma. It is important to ensure that NPG neoplasia is not overlooked if cases of CD10+ carcinoma are to be detected at an early stage.

Overexpression of inducible nitric oxide synthase and accumulation of 8-OHdG in nasopharyngeal carcinoma.

AIMS: Nitric oxide (NO), produced by inducible NO synthase (iNOS), has been suggested to cause oxidative stress, leading to 8-hydroxydeoxyguanosine (8-OHdG) accumulation and subsequent transversion mutation of DNA. The aim was to evaluate iNOS expression and the status of oxidative stress in nasopharyngeal carcinoma (NPC). METHODS AND RESULTS: Seventy-three cases of NPC were investigated to examine the immunohistochemical expression of iNOS, 8-OHdG and latent membrane protein-1 (LMP-1) and Epstein-Barr virus-encoded small RNA (EBER) expression using in situ hybridization. iNOS mRNA expression and p53 gene mutations were also assessed. Overexpression of iNOS, LMP-1 and EBER was observed in 62 (84.9%), 28 (38.4%) and 53 (72.6%) cases respectively. p53 gene mutation was found in 10 of 73 (13.7%) cases. Immunohistochemical iNOS expression was associated with the 8-OHdG labelling index, iNOS mRNA expression and p53 gene alteration (P < 0.0001, P = 0.016 and 0.0082 respectively). CONCLUSIONS: Our present findings suggest that the expression of iNOS induces oxidative stress in NPC. Although the presence of p53 mutation was associated with iNOS overexpression, the type of acid-base change of p53 was transition, but not transversion, which suggests that the p53 gene is not the direct target of DNA damage by 8-OHdG accumulation.

The accumulation of angiostatin-like fragments in human prostate carcinoma.

PURPOSE: Angiostatin, a potent inhibitor of angiogenesis and, hence, the growth of tumor cell metastasis, is generated by a proteolytic enzyme from plasminogen. However, its localization and specific enzymes have yet to be ascertained in human tissue. EXPERIMENTAL DESIGN: To elucidate the generation and the localization of angiostatin in prostate carcinoma, we examined angiostatin generation in a panel of human prostate cancer cell lines and performed immunohistochemistry with the antibodies to angiostatin and prostate-specific antigen (PSA), a potent proteolytic enzyme of angiostatin in 55 cases of prostate carcinoma. RESULTS: We demonstrated that the lysates of human prostate carcinoma cell lines could generate angiostatin-like fragments from purified human plasminogen but could not generate angiostatin in the absence of exogenous plasminogen. The fragmented proteins were reacted with the monoclonal antibody specific for plasminogen lysine-binding site 1 (LBS-1). Immunohistochemically, the intracytoplasmic immunostaining of LBS-1 was positive in 87.3% (48 of 55) of prostate carcinoma cases, and the immunostaining of miniplasminogen was negative in all cases. There was a significant relationship between the positive immunostaining of LBS-1 and Gleason score (P = 0.0007). The intracytoplasmic immunostaining of PSA was positive in 37.0% (20 of 54) of prostate carcinoma cases, but there was no significant relationship between the expression of PSA and Gleason score, or between the positive immunostaining of LBS-1 and PSA. CONCLUSIONS: These findings suggest that angiostatin is generated by prostate carcinoma cells and is accumulated within the cytoplasm. In addition, the generation of angiostatin-like fragments was correlated with tumor grade; however, PSA may not be the only enzyme for angiostatin generation in human prostate carcinoma.

Increased expression of an ATP-binding cassette superfamily transporter, multidrug resistance protein 2, in human colorectal carcinomas.

The expression of ATP-binding cassette superfamily transporter genes, such as P-glycoprotein/multidrug resistance (MDR) 1 and MDR protein (MRP) 1, is often up-regulated in various tumor types and is involved in responses to some anticancer chemotherapeutic agents. Five human MRP subfamily members (MRP2-6) with structural similarities to MRP1 have been identified. The relationships between MRP2-6 mRNA levels and drug resistance are not well understood. Data on 45 patients with colorectal cancer were analyzed. Of the ATP-binding cassette superfamily genes, we asked whether mRNA levels of MDR1, MRP1, MRP2, and MRP3 correlated with drug resistance to anticancer agents. For this analysis, we used quantitative reverse transcription-PCR, and the sensitivity to anticancer agents in surgically resected colon carcinomas was determined using the in vitro succinate dehydrogenase inhibition test. MDR1, MRP1, and MRP3 were highly expressed in normal colorectal mucosa, and the relative mRNA levels of MDR1, MRP1, and MRP3 in cancerous tissues compared with noncancerous tissues were decreased or unchanged. By contrast, MRP2 mRNA expression was low in normal colorectal mucosa and specifically increased in cancer regions compared with noncancerous regions. Of the anticancer agents prescribed for patients with colorectal cancers, including doxorubicin, mitomycin C, cisplatin, 5-fluorouracil, etoposide, and a camptothecin derivative, mRNA expression of MRP2 was significantly associated with resistance to cisplatin. MRP2 may be important for resistance to cisplatin treatment in colorectal cancer.

High expression of the Cap43 gene in infiltrating macrophages of human renal cell carcinomas.

We used suppression subtractive hybridization to identify highly expressed genes in the cancerous region of human renal cell carcinoma (RCC) compared with noncancerous tissue. Nine genes were identified to show increased expression in the cancerous region compared with the noncancerous region. The nine genes included thymosin beta4, secreted protein acidic and rich in cysteine (SPARC), Cap43, ceruloplasmin, serum amyloid A, osteopontin, heat shock protein 90 (HSP90), LOT1, and casein kinase I. Of these 9 genes, in situ hybridization with 10 clinical samples consistently showed a strong expression of Cap43 mRNA in infiltrating macrophages in RCCs, but not in cancer cells proliferating in an alveolar pattern. However, Cap43 mRNA was also apparently detected in epithelial cells of the renal proximal tubuli in noncancerous tissue. The higher expression of the Cap43 gene in the cancerous region of RCCs appears to depend on macrophage infiltration. Moreover, treatment with phorbol ester resulted in enhanced expression of the Cap43 gene in human monocytic cells in vitro. The expression of the Cap43 gene in infiltrating macrophages is discussed in association with the differentiated or activated status of monocyte/macrophage.

Nuclear factor-kappaB p65 (RelA) transcription factor is constitutively activated in human gastric carcinoma tissue.

PURPOSE: Activation of transcription factor nuclear factor-kappaB (NF-kappaB) has been shown to play a role in cell proliferation, apoptosis, cytokine production, and oncogenesis. The purpose of this study was to determine whether NF-kappaB is constitutively activated in human gastric carcinoma tissues and, if so, to determine any correlation between NF-kappaB activity and clinicopathological features of gastric carcinoma. EXPERIMENTAL DESIGN: NF-kappaB activation was determined by immunohistochemical analysis of formalin-fixed, paraffin-embedded specimens from 64 gastric carcinoma patients. We quantified nuclear staining of RelA as a marker of NF-kappaB activation. RESULTS: Nuclear translocation of RelA was significantly high in tumor cells in comparison to that in adjacent normal epithelial cells (22.5 +/- 2.4% versus 8.6 +/- 1.5%, P < 0.0001). There was a significant correlation between NF-kappaB activation (nuclear translocation of RelA) and expression of urokinase-type plasminogen activator, an invasion-related factor and target of NF-kappaB in tumor cells (rho = 0.393; P = 0.0013). NF-kappaB activation was correlated with tumor invasion-related clinicopathological features such as lymphatic invasion of tumor cells (P = 0.0126), depth of invasion (P = 0.0539), peritoneal metastases (P = 0.0538), and tumor size (P = 0.0164). CONCLUSIONS: Collectively, the data show that NF-kappaB is constitutively activated in human gastric carcinoma tissues and suggest that NF-kappaB activity is related to tumor progression due to its transcriptional regulation of invasion-related factors such as urokinase-type plasminogen activator.

Telomerase elevation in pancreatic ductal carcinoma compared to nonmalignant pathological states.

Telomerase activity was measured in surgically resected tissues of 20 human pancreatic ductal carcinomas, 12 adenomas, 5 pancreatitis tissues, 14 normal pancreatic ducts, and 13 normal pancreatic tissues (primarily made up of acinar cells) using a PCR-based telomerase assay. Relative telomerase activity was expressed as the equivalent telomerase intensity of the number of cells of a human pancreatic cancer cell line, MIA PaCa-2, per microgram of protein in the tissue samples. The median value (25th percentile, 75th percentile) of relative telomerase activity in pancreatic carcinomas was 13.2 (3.58, 244), which was significantly higher relative to normal tissues, normal ducts, pancreatitis tissues, and adenomas (P < 0.0001). When the cutoff value of relative telomerase activity was set at 1.00 and 3.00, the positivity rates of telomerase activity in pancreatic ductal carcinomas were 100 and 80%, respectively. Some of the adenoma samples displayed a weak telomerase ladder. However, when semiquantitatively analyzed, the relative telomerase activity of all adenoma tissues was less than 1.00 equivalent cells per microgram protein of the tissues, which was equivalent to the values encountered in normal ducts. Thus, our results indicate that reactivation of telomerase may occur at a late stage of pancreatic ductal carcinogenesis. Therefore, telomerase may be a specific marker for distinguishing pancreatic cancer from pancreatitis and adenomas.

Nuclear expression of YB-1 protein correlates with P-glycoprotein expression in human osteosarcoma.

The Y-box-binding protein, YB-1, is a member of the DNA-binding protein family. It binds to the Y-box, an inverted CCAAT box, in the promoter region of the human multidrug resistance 1 gene, which encodes P-glycoprotein (P-gp). Nuclear localization of YB-1 protein has been reported to be associated with the intrinsic expression of P-gp in human breast cancer. We studied the immunohistochemical expression of YB-1 protein in 69 untreated biopsy specimens of conventional osteosarcomas and compared it with the expression of P-gp. Furthermore, cell proliferation, as determined by the MIB-1-labeling index (MIB-1-LI), was measured by immunohistochemistry. In all 69 untreated osteosarcomas, YB-1 protein was expressed in the cytoplasm. In 32 of 69 (46%) cases, YB-1 was also localized in the nucleus. The expression of P-gp was evident in 23 of these 32 cases, and there was a significant correlation between the nuclear expression of YB-1 and P-gp expression (P < 0.0001). Chondroblastic osteosarcoma expressed YB-1 in the nucleus more frequently (eight of nine cases) than did other types of osteosarcoma, whereas P-gp was also frequently expressed in chondroblastic subtype. There was no correlation between the nuclear expression of YB-1 and histological grade. The MIB-1-LI was significantly higher in cases showing the nuclear expression of YB-1 (MIB-1-LI averaged 22.56 in cases with only cytoplasmic expression of YB-1 but averaged 28.20 in cases with cytoplasmic and nuclear expression of YB-1; P = 0.0477). In human osteosarcoma, nuclear localization of YB-1 protein was associated with the expression of P-gp, suggesting that YB-1 could be a prognostic marker for multidrug resistance in osteosarcoma.

Noradrenaline-secreting glomus jugulare tumor with cyclic change of blood pressure.

A glomus jugulare tumor secreted a large quantity of noradrenaline (NA) and produced symptoms of tinnitus, palpitation, sweating, and labile hypertension. The NA content of the tumor was 0.75 mg/gm of tissue. Electron microscopical study of the tumor demonstrated many membrane-limited osmiophilic granules. This indicates the capacity of the tumor not only to synthesize but also to store NA in the tumor. Continuous blood pressure recording showed a cyclic change of blood pressure with a cycle length of 10 to 17 minutes that terminated after intravenous doses of phentolamine (0.1 mg/kg) or diazoxide (4.5 mg/kg) and surgical removal of the tumor.

Clinical characteristics and the prognosis of rhabdomyosarcoma - a report from the Study Group for Pediatric Solid Malignant Tumors in the Kyushu Area, Japan.

AIM: There have been no nationwide group studies for patients with rhabdomyosarcoma in Japan. This study aims to assess the actual state of treatments and their outcome. PATIENTS AND METHODS: From 1982 to 1996, 79 rhabdomyosarcomas were registered by the Study Group for Pediatric Solid Malignant Tumors in the Kyushu Area. The prognostic factors and treatments were assessed based on the 5-year survival rate. The staging was done according to the Intergroup Rhabdomyosarcoma Study (IRS) Clinical Grouping Classification. RESULTS: The 5-year survival rate for all patients was 39.1 %. The survival rates for each factor were as follows, according to 1) group; 77.8 % for Group I, 51.9 % for Group II, 33.7 % for Group III, and 20.2 % for Group IV; 2) primary site: 56.3 % for the head and neck, 43.8 % for the parameningeal region, 12.5 % for the extremity, 58.3 % for the genitourinary region, and 30.5 % for the others; 3) histology: 35.8 % for the embryonal type, 36.8 % for the alveolar type. CONCLUSIONS: Altogether, the outcome of this study was poor. To improve outcomes, a new nationwide group study for rhabdomyosarcoma, which we belong to, has just started in Japan.

Localization and quantification of proliferating cells during rat fracture repair: detection of proliferating cell nuclear antigen by immunohistochemistry.

Bilateral femurs of 12-week-old female Sprague-Dawley rats were fractured, and the fractured femurs were harvested 36 h, 3, 7, 10, and 14 days after the fracture. Localization of cell proliferation in the fracture calluses was investigated using immunohistochemistry with antiproliferating cell nuclear antigen (PCNA) monoclonal antibodies. Thirty-six hours after the fracture, many PCNA-positive cells were observed in the whole callus. The change was not limited to mesenchymal cells at the fracture site where the inflammatory reaction had occurred, but extended in the periosteum along almost the entire femoral diaphysis where intramembranous ossification was initiated. On day 3, periosteal cells or premature osteoblasts in the newly formed trabecular bone during intramembranous ossification still displayed intense staining. On day 7, many premature chondrocytes and proliferating chondrocytes were PCNA positive. Endochondral ossification appeared on days 10 and 14, and the premature osteoblasts and endothelial cells in the endochondral ossification front were stained with anti-PCNA antibodies. Quantification of PCNA-positive cells was carried out using an image analysis computer system, obtaining a PCNA score for each cellular event. The highest score was observed in the periosteum early after the fracture near the fracture site. Immunohistochemistry using anti-PCNA antibodies showed that the distribution of proliferating cells and the degree of cell proliferation varied according to the time lag after the fracture, suggesting the existence of local regulatory factors such as growth factors, and that significant cell proliferation was observed at the beginning of each cellular event.

Hypercalcemia caused by ectopic production of parathyroid hormone in a patient with papillary adenocarcinoma of the thyroid gland.

Hypercalcemia and elevation of a serum PTH level (9800 pg/mL (normal: 160-520) were found in a 72-yr-old woman who had a lung cancer. She underwent pulmonary lobectomy for a suspected PTH-producing lung cancer. However, hypercalcemia and elevation of the serum PTH level were persistent postoperatively. Subsequent examination, using parathyroid scintiscanning, revealed a hot spot in the right lower part of the thyroid gland, suggesting hypercalcemia caused by a parathyroid tumor. She underwent bilateral exploration of the neck; however, four apparently normal parathyroid glands were seen. Therefore, hemithyroidectomy was performed for the possibility of an intrathyroidal parathyroid adenoma. Serum calcium and PTH levels declined after this operation. A nodular lesion was found in the cut sections of the resected specimen, which was consistent with the result of the scintiscanning. Histological examinations revealed a papillary adenocarcinoma of the thyroid gland, and the PTH-immunoreactivity in the tumor cells was confirmed. These findings strongly suggest that PTH could be produced ectopically by the papillary adenocarcinoma of the thyroid gland.

A comparative study of fibrous dysplasia and osteofibrous dysplasia with regard to Gsalpha mutation at the Arg201 codon: polymerase chain reaction-restriction fragment length polymorphism analysis of paraffin-embedded tissues.

Fibrous dysplasia and osteofibrous dysplasia are both benign fibro-osseous lesions of the bone and are generally seen during childhood or adolescence. Histologically, the features of these bone lesions sometimes look quite similar, but their precise nature remains controversial. Mutation of the alpha subunit of signal-transducing G proteins (Gsalpha), with an increase in cyclic adenosine monophosphate (cAMP) formation, has been implicated in the development of multiple endocrinopathies of the Albright-McCune syndrome and in the development of fibrous dysplasia. We studied Gsalpha mutation at the Arg201. codon in seven cases of fibrous dysplasia (six monostotic lesions and one polyostotic lesion) and seven cases of osteofibrous dysplasia using formalin-fixed, paraffin-embedded tissue, by means of polymerase chain reaction-restriction fragment length polymorphism and direct sequencing analysis. All of the seven cases of fibrous dysplasia showed missense point mutations in Gsalpha at the Arg201 codon that resulted in Arg-to-His substitution in three cases and Arg-to-Cys substitution in four cases. On the other hand, the seven cases of osteofibrous dysplasia and the normal bone used as a control showed no such mutation. These data suggest that fibrous dysplasia and osteofibrous dysplasia have different pathogeneses and that the detection of Gsalpha mutation at the Arg201 codon is quite useful for distinguishing between these lesions.

Inflammatory fibroid polyp of the stomach. A special reference to an immunohistochemical profile of 42 cases.

Forty two cases (46 lesions) of inflammatory fibroid polyp (IFP) of the stomach were reviewed histologically and studied immunohistochemically. The paraffin sections were stained with a panel of antibodies against alpha-smooth-muscle actin, HHF-35, desmin, vimentin, lysozyme, alpha-1-antitrypsin, alpha-1-antichymotrypsin, KP1, Mac 387, S-100 protein, neuron-specific enolase, factor VIII RAg, and with Ulex europaeus agglutinin I. The lesions ranged in size from 0.3 to 3.5 cm with a mean of 1.2 cm. Forty (87.0%) IFPs occurred in the antrum, five in the gastric body, and one in the cardia. In all but two lesions, the mucosal layer was involved, and 20 (43.5%) lesions were entirely restricted to the mucosa. All 46 IFPs tested diffusely positive with vimentin. Positive reactions for alpha-smooth-muscle actin and HHF-35 were observed in 12 (26.1%) and 10 (21.7%) IFPs, respectively. Two lesions with alpha-smooth-muscle actin and one lesion with HHF-35 showed a diffuse staining. Seventeen (37.0%) lesions were focally positive for KP1, and seven (15.2%) IFPs were focally positive for Mac 387. All other antibodies and agglutinin were negative with the proliferating cells. The results of this study confirmed (a) the presence of myofibroblastic and histiocytic lines of differentiation in addition to the main fibroblastic features for the main cellular component in IFP, and (b) the heterogeneity of the immunoprofile of IFP.

Fibrosarcoma versus fibromatoses and cellular nodular fasciitis. A comparative study of their proliferative activity using proliferating cell nuclear antigen, DNA flow cytometry, and p53.

We analyzed the proliferative activities, immunoreactivity of the p53 protein, and aneuploidy in patients with benign and malignant fibrous lesions, including 19 with nodular fasciitis (cellular type) (6-88 years old, mean 42.9), 11 with abdominal fibromatoses (22-74 years old, mean 37.9), 13 with extraabdominal fibromatoses (2-38 years old, mean 19.5), and 23 with fibrosarcomas (adult type: 16-71 years old, mean 47.3; infantile type: 3 months to 9 years, mean 2.9) using immunohistochemistry to determine proliferating cell nuclear antigen (PC10) and p53 protein (CM1) as well as performing DNA flow cytometry. The proliferating cell nuclear antigen (PCNA) score was measured as the ratio of PCNA-positive nuclear size/total nuclear size determined by an image analysis computer system. The distribution pattern of the PCNA-positive cells was uneven in each instance of nodular fasciitis, in contrast to the distribution in abdominal fibromatosis, extraabdominal fibromatosis, and fibrosarcoma. Both fibrosarcoma (28.4 +/- 20.0) and nodular fasciitis (33.6 +/- 20.9) exhibited a larger value and a greater variation in the PCNA score than did either abdominal (13.5 +/- 14.5) or extraabdominal fibromatosis (19.9 +/- 21.5). Abdominal fibromatosis exhibited a smaller value and less variation in the score. In short, the PCNA score did not correlate with the malignant potential. The proliferative index (S + G2 + M fraction) in fibrosarcoma was significantly higher than in either nodular fasciitis or abdominal fibromatosis. Aneuploidy was detected in five cases (26%) of fibrosarcoma, while six (26%) fibrosarcomas showed p53 positivity. Furthermore, p53-positive patients had a worse survival (0.01 < p < 0.05), and p53 positivity correlated with the proliferative index (p < 0.01). In conclusion, the PCNA score simply indicates the proliferative activity independent of malignant potential. On the other hand, p53 positivity, proliferative index, and aneuploidy are all indicators of malignant potential in fibroblastic lesions, and p53 positivity may reflect a poor prognosis.

Colorectal counterpart of gastric depressed adenoma. A comparison with flat and polypoid adenomas with special reference to the development of pericryptal fibroblasts.

The histological features of 28 depressed adenomas (DAs) were compared with those of 40 flat adenomas (FAs) without a central depression and those of 29 polypoid adenomas (PAs), with special reference to the development of pericryptal fibroblasts (PCFs), using immunohistochemical staining for muscle-specific actin (HHF-35). The DAs were composed of a crowded collection of adenomatous tubules with smaller diameters than those of the PAs. With regard to PCF development, the DAs had poorly developed PCFs; PCF (-), (+), and (++) numbered 12 (43%), 16 (57%), and 0 (0%), respectively. On the other hand, the nondepressed adenomas (PAs and FAs) had well-developed PCF; PCF (-), (+), and (++) numbered 5 (7%), 35 (51%), and 29 (42%), respectively. In addition, the number of PCFs seemed to decrease in the sequence of PAs, followed by FAs and DAs. According to our results, the DAs had a characteristic histological architecture together with poorly developed PCFs features, which distinguished them from the PAs. In conclusion, the depressed adenomas were considered a subtype of the flat adenomas. The depletion of PCFs seems to correlate with the depressed growth of the adenoma.

Squamous cell carcinoma arising in mature cystic teratoma of the ovary. Clinicopathologic and topographic analysis.

Clinical and pathologic features of 28 patients with squamous cell carcinoma (SCC) arising in mature cystic teratoma (MCT) of the ovary were analyzed. The overall 5-year survival rate of these patients was 52%. Clinical staging (Stage I versus Stages II or more), histologic differentiation (well versus moderately or poorly differentiated SCC), and the presence of vascular invasion were factors affecting the prognosis of these patients. In 11 tumors, including 2 of the 4 examined in stepwise serial sections, the SCC was considered to have originated from a columnar epithelium (ciliated or nonciliated) or from a metaplastic squamous epithelium. On the other hand, no SCC was a direct transition from the ordinary epidermis of the teratomatous skin tissue. These results strongly support the proposal that SCC arising in MCT derives from the columnar epithelium.

Epithelioid hemangioma versus Kimura's disease. A comparative clinicopathologic study.

A clinicopathologic and immunohistochemical study of eight cases of epithelioid hemangioma and 11 cases of Kimura's disease was performed. Patients with epithelioid hemangioma (EH) ranged in age from 15 to 56 years (mean, 37 years) and had small papular or nodular lesions occurring most often on the face and scalp. The lesions were less than 2.0 cm in diameter. There were irregularly hypertrophic vascular structures with swollen endothelial cells and of a variable lymphoid infiltrate with eosinophils. The clustering of small vessels around the arteries or veins was another distinctive feature. Arteriovenous shunts were evident in three lesions. Patients with Kimura's disease, however, presented large solitary or multiple nodules occurring most commonly in the periauricular region. Six patients had a history of regional lymphadenopathy; three patients had eosinophilia of the peripheral blood. Microscopically, the distinctive features were of numerous lymphoid follicles and a salient eosinophilic infiltrate. These lymphoid follicles possessed distinct germinal centers and contained an increased number of dendritic cells. Although some small-vessel proliferation was noted, it was not as distinctive as for patients with epithelioid hemangioma. We conclude from this study that the two conditions should be considered different entities.

Sclerosing adenosis of the prostate. Histopathologic and immunohistochemical analysis.

A prostatic lesion, histologically identical to sclerosing adenosis of the breast, was found in five (1.9%) of 263 patients who underwent transurethral resection, open prostatic adenectomy, radical prostatectomy, or total cystoprostatectomy. This uncommon lesion was a localized proliferation of crowded small glands, small solid nests, and individual cells embedded in a cellular stroma, mimicking a small acinar prostatic adenocarcinoma. The proliferating glands were lined by a single layer of secretory cells surrounded by an eosinophilic membranous structure. Basal cells were disclosed in individual glands or as small nests and even individual cells with immunostainability for basal cell-specific cytokeratin (EAB903), S-100 protein, and muscle-specific actin (HHF35). These findings indicate the benign nature of the lesion with myoepithelial differentiation of the basal cells. In contrast, all 25 small acinar adenocarcinomas examined as controls lacked positive stains for the above three antibodies, verifying the usefulness of these antibodies to distinguish between this benign lesion from adenocarcinoma.

Vimentin-positive gastric carcinomas with rhabdoid features. A clinicopathologic and immunohistochemical study.

We studied 71 patients with solid-type gastric adenocarcinoma selected from 5,437 surgically resected specimens during the period from 1975 to 1988; six had vimentin-positive adenocarcinomas, and five of these were advanced. One was at an early stage. All six tumors showed the same histologic features and had either a diffuse or alveolar arrangement, with tumor cells having either poor or no cohesiveness. Many tumor cells were round to polygonal, with eosinophilic or clear cytoplasm and large, eccentric vesicular nuclei, as seen in malignant rhabdoid tumors of the kidney. In all cases, the cytoplasm showed coexpression of vimentin and cytokeratin as revealed by double immunostaining. Four of the five cases with advanced carcinoma died of the disease 1 to 6 months after surgery. The cases with vimentin-positive tumors had significantly poorer prognoses than those with vimentin-negative tumors. We also studied adenocarcinomas of various histologic types randomly selected from our file (160 intestinal type and 69 diffuse type of Lauren) but failed to detect any vimentin positive ones. These results indicate that vimentin is expressed in some of the solid-type adenocarcinomas, which have a poor prognosis, and indicating that rhabdoid-like cells may be found in a variety of adenocarcinomas of the stomach.