Kenichi Tazawa

An immunohistochemical and clinicopathological study of gastrointestinal stromal tumors

Immunohistochemical and clinicopathological features of 58 gastrointestinal stromal tumors (GIST) were studied. One occurred in the esophagus, 41 in the stomach, nine in the small intestine, and seven in the large intestine. By using indirect immunoperoxidase staining for Cajal cell markers (c‐kit protein and CD34), smooth muscle markers (α‐smooth muscle actin, desmin, heavy caldesmon and calponin) and Schwann cell markers (S‐100 protein and Leu 7), GIST were classified into five groups, such as Cajal cell type (n = 9), myogenic type (n = 5), Schwann cell type (n = 2), mixed cell type (n = 40) and undifferentiated type (n = 2). c‐kit Protein (42/58; 72%) and CD34 (45/58; 78%) were commonly and diffusely expressed in GIST. Novel smooth muscle markers, caldesmon (29/58; 50%) and calponin (18/58; 31%), were useful in detecting myogenic characters of GIST. S‐100 protein was expressed in 16 (28%) tumors, two of which were also reactive with Leu 7 (CD57). Three small bowel tumors with skeinoid fibers expressed the Cajal cell markers, and were categorizable in GIST. Clinicopathological analyses using aggressive (n = 21) and non‐aggressive (n = 21) GIST indicated that the malignant potential was correlated with the intestinal location, large tumor size, high cellularity, necrosis, solid (non‐interlacing bundled) pattern of growth, negativity of c‐kit protein and/or CD34, high mitotic count, and high MIB‐1 labeling.

Localization of prostate-specific antigen-like immunoreactivity in human salivary gland and salivary gland tumors

Immunoreactivity of prostate‐specific antigen (PSA), a kallikrein‐like enzyme present in the seminal plasma, was demonstrated by indirect immunoperoxidase staining using a PSA antiserum in the apical cytoplasm along the luminal border of small‐sized duct epithelial cells of the major salivary (parotid and submandibular) gland of both sexes (56/56, 100%). No PSA‐like immunoreactivity was seen in large‐sized duct epithelial cells and acinar cells. Minor salivary gland ducts were negative. When inflammatory and atrophic changes were observed, ductal expression of PSA‐like immunoreactivity was decreased (12/37, 32%) and the site of intracellular localization often became diffusely cytoplasmic. The immunoreactivity was absorbed by human seminal plasma. Immunoreactivities of prostatic acid phosphatase and sex hormone receptors were undetectable in the salivary gland. Twenty‐nine (34%) of 86 salivary gland tumors with ductal differentiation were immunoreactive for PSA mainly in the cytoplasm. A PSA monoclonal antibody ER‐PR8 detected immunoreactivity in the prostate but not in the salivary glands or their tumors. Prostate‐specific antigen‐like immunoreactivity in small‐sized (intercalated) duct epithelial cells of the major salivary gland and their tumors may be due to cross‐reactivity of the antiserum with kallikrein‐like substances.

Splenic artery aneurysm associated with systemic lupus erythematosus: Report of a case

We herein report on a 64-year-old Japanese female patient who presented with a splenic artery aneurysm (SAA) associated with systemic lupus erythematosus (SLE). The saccular aneurysm, which measured 3 cm in diameter, was located in the proximal third of the splenic artery from the pancreas with a portosystemic shunt. A double ligation of the splenic artery (the distal and proximal sides of the aneurysm) was performed without a splenectomy. The postoperative course showed acute pancreatitis without either splenic infarction or portal thrombus. To our knowledge, the closed association of SLE with an aneurysmal dilatation of the splenic artery has not been previously reported. Both the pathogenesis and the management of SAA associated with SLE are discussed following the presentation of this case. This is the first reported case of SAA associated with SLE.

TYPE VI COLLAGEN IMMUNOREACTIVITY IN SKEINOID FIBERS IN SMALL INTESTINAL STROMAL TUMORS

By immunoperoxidase analysis for types I to VI collagen, elastin, cytoskeletal components and some glycoproteins, we found type VI collagen immunoreactivity in amorphous eosinophilic deposits (skeinoid fibers) in three small intestinal stromal tumors. Negative results were obtained for types I, II, III, IV and V collagen, elastin, laminin, ubiquitin, intracellular filaments such as actin, desmin, vimentin, calponin and caldesmon, and glycoprotein such as lysozyme, factor XIIIa, β2‐microglobulin, α1‐antitrypsin and α1‐antichymotrypsin. In two lesions, the periodic acid‐Schiff‐positive skeinoid fibers were also focally labeled for amyloid P component.

EFFECT OF PROLONGED STAINING WITH HEMATOXYLIN ON DETECTING HELICOBACTER PYLORI IN HEMATOXYLIN-EOSIN-STAINED GASTRIC MUCOSA

Helicohacter pylorl (H. pylorl) Is ldentlflable in hematoxyiin‐eosin (HE)‐stalned preparations, particuularly under a prolonged hematoxylln staining condition. The stalnlng intensity of H. pylori bodies was Increased when the hemetoxylln stalnlng period was doubled from 5 min, the routine period of Meyers hematoxyiin stalnlng, to 10 min. The stalning intenstty of the background eplthellal nuclei was only mildly increased. Hematoxylin‐eosin staining employing a prolonged hematoxylin staining period gave detedablllty of H. pylori comparable to May‐Glemsa and lmmunoperoxldase staining. The modified HE method is thus Very useful and practical for identifying H. pylori in routine gastric biopsy specimens.

Possible involvement of glucose transporter 3 and 4 in esophageal leiomyoma with unusual high uptake of fluorine-18-fluorodeoxyglucose: three case reports

There were esophageal benign leiomyomas that showed unusual uptake of fluorine-18-fluorodeoxyglucose (FDG). Three patients received enucleation or resection of esophageal submucosal tumors and these were confirmed as benign leiomyomas pathologically. Preoperative FDG-PET examination of the two patients revealed that maximum standardized uptake values (SUVmax) of the tumor were 5.83 and 5.57. Both tumors had strong expression of glucose transporter (Glut)-3 and Glut-4. The other one patient showed low uptake of FDG and weak expression of Glut-3 and Glut-4. Interestingly, all three tumors had negative expression of Glut-1 and Glut-2. Furthermore, cultured leiomyoma cells (TYLeio-3) from the patients with high uptake of FDG had strong expression of Glut-3, weak expression of Glut-4 and no expression of Glut-1. Our results suggested that the expression of Glut-3 and Glut-4, but not Glut-1, may be one of the reasons for unusual uptake of FDG in benign esophageal leiomyoma.

A Case of Adenoid Squamous Cell Carcinoma of the Breast Skin

We report a case of a 45-year-old Japanese woman with adenoid squamous cell carcinoma (ASCC) of the left breast skin. The patient had showed a large mass in the left breast region with axillary swelling about 1 year before admission. Grossly, the tumor was an extensively ulcerated and elevated lesion measuring 15X16X5 cm. Based on the tumor biopsy and cytologic examination of the axillary lymph nodes, squamous cell carcinoma (SCC) was diagnosed. No evidence of distant metastasis was identified. A modified radical mastectomy with left axillary node dissection was performed. Microscopically, the resected tumor showed an invasive proliferation of atypical squamous cells with marked keratinization. At the periphery of the tumor, an adenoid growth pattern was frequently seen with a transitional area showing squamous cell carcinoma and adenoid growth components. ASCC was diagnosed. A transition between the overlying squamous cell epithelium and squamous cell carcinoma component was also seen, thus the tumor was thought to have originated from the breast skin. The patient died of respiratory failure due to multiple lung metastasis about 1 month after the mastectomy. Tumor rarely originates at the breast region to include both the mammary glands and breast skin. The pathogenesis and management of ASCC are discussed following the presentation of this case.

KLF4 Improve Prognosis of Triple-negative Breast Cancer by Suppression of Epithelial-mesenchymal Transition

Background: The prognostic value of KLF4 in triple negative breast cancer (TNBC) was described. Here we report an analysis of KLF4 expression in peripheral blood circulating tumor cells (CTCs) from patients with TNBC, which provided evidence that KLF4 negatively regulates the metastasis and growth of TNBC. Method: We assessed the expression levels of KLF4 in 84 patients with TNBC by immunohistochemical staining and studied the patterns of metastasis/recurrence clinicopathologically. In addition, CTCs in the peripheral blood of TNBC patients were identified and compared with primary lesions in terms of KLF4 expression. Moreover, the expression of KLF4 was inhibited by transfecting cultured TNBC cells (MDA-MB231) with the small interfering RNA (siRNA) of KLF4 to analyze the effects of KLF4 on cell proliferation and epithelial-mesenchymal transition (EMT) -like changes. Results: In the 84 patients with TNBC, higher KLF4 expression was associated with significantly better overall survival (OS) and disease-free survival (DFS). An analysis of KLF4 expression in CTCs of the TNBC patients showed that KLF4 expression was lower in CTCs than in cancer cells in primary lesions. TNBC cells (MDA-MB231) with inhibited KLF4 expression exhibited a greater ability to growth than controls. These cells also underwent EMT-like changes with reduced expression of epitherial factors such as E-cadherin. Treating these TNBC cells with eribulin resulted a reduction of the expression of stem cell/EMT markers. Conclusion: TNBC patients with reduced KLF4 expression had poor outcomes. The results of our experiments suggest the expression of KLF4 is one of the important factors that inhibit the EMT and growth of TNBC.

Adenocarcinoma in long-segment Barrett's esophagus 44 years after total gastrectomy.

Although Barretts esophagus may occur without gastric acid, Barretts adenocarcinoma after total gastrectomy is rare. Here, we present Barretts adenocarcinoma in long-segment Barretts esophagus after total gastrectomy. The patient was a 74-year-old male who underwent total gastrectomy 44 years ago. An endoscopic examination revealed long-segment Barretts esophagus starting 17 cm from the incisors and continuing 20 cm to esophagojejunostomy, with irregular mucosa 27–31 cm from the incisors. Pathological diagnosis of a biopsied specimen was adenocarcinoma. We performed subtotal esophagectomy with lymph node dissection in the prone position and reconstructed the esophagus with ileocolic interposition. Postoperative pathological diagnosis from a Barretts epithelial section was well differentiated adenocarcinoma. This case had the longest interval from total gastrectomy and smallest oral margin of Barretts epithelium. Our case suggested that careful surveillance is needed for patients exhibiting recurrent bile reflux following total gastrectomy.