Shizuoka City Shimizu Hospital

Shimizu Ku, Japan

Shizuoka City Shimizu Hospital

Shimizu Ku, Japan

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Because there have been no reports on the incidence and expressions and mutations of KIT and PDGFRA in small cell neuroendocrine carcinoma (SCNEC) of the prostate, the author surveyed archival specimens of 2,642 prostatic specimens (biopsy, 1,503 cases; transurethral resection, 1,009 cases; prostatectomy, 130 cases). Of these, 706 cases were malignant tumors. In equivocal cases (n = 16) of Gleason 5 adenocarcinoma resembling SCNEC, several neuroendocrine markers were immunohistochemically examined. As the results, four cases of SCNEC were identified; therefore the incidence of SCNEC was 0.5% of all prostatic malignancies. All the four cases were biopsies. The remaining 686 cases were adenocarcinomas. In case 1 (50 years of age), the SCNEC tumor cells were positive for cytokeratin, P504S, synaptophysin, KIT, and PDGFRA, but negative for PSA, neuron specific enolase, CD56, and TTF-1. In case 2 (70 years of age), the tumor cells were positive for cytokeratin, PSA, P504S, chromogranin, and synaptophysin, but negative for neuron-specific enolase, CD56, TTF-1, KIT, and PDGFRA. In case 3 (72 years of age), the SCNEC tumor cells were positive for cytokeratin, PSA, P504S, synaptophysin, CD56, KIT, and PDGFRA, but negative for neuron-specific enolase, chromogranin, and TTF-1. In case 4 (81 years of age), the SCNEC tumor cell were positive for cytokeratin, PSA, P504S, chromogranin, synaptophysin, neuron-specific enolase, KIT, and PDGFRA, but negative for CD56 and TTF-1. A molecular genetic analysis using PCR-direct sequencing showed no mutations of KIT (exons 9, 11, 13, and 17) and PDGFRA (exons 12 and 18) genes in three informative cases of SCNEC. The present cases were the first of prostatic SCNEC with an examination of KIT and PDGFRA expression and KIT and PDFGRA gene mutations. © 2011 Wiley Periodicals, Inc.


Terada T.,Shizuoka City Shimizu Hospital
International Journal of Clinical and Experimental Pathology | Year: 2013

The author reviewed 910 cases of consecutive esophageal biopsies in the last 15 year in the pathology laboratory of our hospital. There were 693 normal mucosa and benign lesions (76.2%) and 217 malignant lesions (23.8%). No significant changes were recognized in the esophagus in 50 biopsies (5.5%). In benign lesions, the number and frequency (percentages) were as follows: 263 chronic esophagitis (28.9%), 98 heterotopic gastric mucosa (10.8%), 3 heterotopic colonic mucosa (0.3%), 71 glycogenic acanthosis (7.8%), 68 candidiasis (7.5%), 35 benign ulcer (3.8%), 41 squamous papilloma (4.5%), 4 granular cell tumor (0.4%), 1 tubular adenoma (0.1%), 2 cytomegalovirus esophagitis (0.2%), 3 leiomyoma (0.3%), 17 basal cell hyperplasia (1.9%), and 37 Barrett's epithelium (4%). In malignant lesions, the number and frequency (percentages) were as follows: 53 mild dysplasia (5.8%), 29 moderate dysplasia (3.2%), 31 severe dysplasia (3.4%), 13 carcinoma in situ (1.4%), 68 squamous cell carcinoma (7.5%), 7 primary adenocarcinoma (0.8%), 1 primary signet ring cell carcinoma (0.1%), 4 primary small cell carcinoma (0.4%), 2 primary amelanotic malignant melanoma (0.2%), 1 primary undifferentiated sarcoma (0.1%), 7 gastric cancer invasion (0.8%), and 1 primary adenoid cystic carcinoma (0.1%). In this article, the clinicopathologic features of these esophageal lesions were described.


Terada T.,Shizuoka City Shimizu Hospital
International Journal of Clinical and Experimental Pathology | Year: 2013

In the current WHO blue book, combined hepatocellular-cholangiocarcinoma (C-HCC-CC) was classified into two types; classical type and type with stem cell features. The latter is extremely rare, and is subcategorized into the following three subtypes; typical subtype, intermediate cell subtype, and cholangiocellular subtype. Recently, intrahepatic cholangiocarcinoma (ICC) with features of ductal plate malformations (DPM) have been reported, and the ICC with DPM was proposed as a subtype of ICC. The author herein reports a case of C-HCC-CC with stem cell features. Characteristically, the CC element showed features of DPM. A 51-year-old man of HBV carrier was found to have high AFP. A laboratory test showed an elevated AFP (395 ng/ml, normal 9-10) and hepatitis B virus-related antigens and antibodies. Liver and ductal enzymes and PIVKAII were within normal ranges. Imaging modalities including CT identified a small liver tumor. Hepatocellular carcinoma (HCC) was suspected, and the resection of the hepatic tumor was performed. Grossly, the liver tumor is well-defined white solid tumor measuring 22x16x23 mm. Microscopically, the tumor was a C-HCC-CC, and was composed of following three elements: well differentiated HCC, well differentiated cholangiocarcinoma (CC), and intermediate tumor element. Characteristically, the CC cells formed tortuous markedly irregular tubules with intraluminal cell projections, bridge formations, intraluminal tumor biliary cells; such features very resembled the ductal plate (DP) and DPM. Immunohistochemically, the cells of CC element were positive for stem cell antigens (KIT (CD117), CD56, EMA, CD34), HepPar1, EpCAM, cytokeratin (CK) CAM5.2, AE1/3, CK34BE12 (focal), CK7, CK8, CK18, CK19, CA19-9, p53, MUC1, MUC2, MUC5AC, MUC6, and Ki-67 (labeling=25%). They were negative for CEA, CK5/6, CK20, NSE, chromogranin, synaptophysin, and p63. No mucins were found by histochemically. The background liver showed chronic hepatitis B (a1, f3). Very interestingly, many DPMs were scattered in the non-tumorous parenchyma. This type of C-HCC-CC with DPM features has not been reported. The author herein proposes that this tumor should be included or added in the C-HCC-CC subtype as C-HCC-CC with stem cell features, DMP subtype.


The expression of NCAM (CD56), chromogranin A, synaptophysin, c-KIT (CD117) and PDGFRA in normal non-neoplastic skin and basal cell carcinoma (BCC) has rarely been investigated. The author immunohistochemically examined the expression of these molecules in 66 consecutive cases of BCC. In non-tumorous skin, NCAM chromogranin A, synaptophysin, c-KIT and PDGFRA expression was seen in the basal cell of the epidermis. NCAM, c-KIT and PDGFRA expression was also seen in the sweat glands and outer cells of hair follicles, but chromogranin and synaptophysin expression was not identified in these structures. In BCC, NCAM expression was seen in 95 % (63/66 cases). Its expression was membranous. Chromogranin A expression was recognized in 27 % (18/66 cases). Its expression was cytoplasmic. Synaptophysin expression was seen in 18 % (12/66 cases). Its expression was membranous and cytoplasmic. c-KIT expression was noted in 93 % (61/66 cases). Its expression was membranous and focally cytoplasmic. PDGFRA expression was seen in 65 % (43/66 cases). Its expression was membranous and cytoplasmic. The expression of these molecules in normal non-tumorous skin is a new finding. The expression of c-KIT and PDGFRA in BCC is also a new finding. In conclusion, the author described the normal (non-neoplastic) distribution of NCAM, chromogranin A, synaptophysin, c-KIT and PDGFRA. In addition, the author showed that, in cutaneous BCC, the expression of NCAM and c-KIT was high (95 and 93 % respectively), PDGFRA was intermediate (65 %), and chromogranin A and synaptophysin was relatively low (27 and 18 %, respectively). © 2013 Springer Science+Business Media New York.


Terada T.,Shizuoka City Shimizu Hospital
International Journal of Clinical and Experimental Pathology | Year: 2013

Leiomyoma of the lung is extremely rare. The entity is not described in WHO blue book. Less than 100 cases of leiomyoma of the lung have been reported in the literature. However, vascular leiomyoma has not been reported in the literature, to the author's best knowledge. Herein reported is the first case of vascular leiomyoma of the lung arising from smooth muscles of the pulmonary artery. A 62-year-old woman (non-smoker) was found to have a small tumor in the upper lobe in the right lung in routine check. Imaging modalities including CT demonstrated no metastatic lesions. Although clinical cytology and biopsy revealed no malignant cell, right upper lobectomy was performed under the clinical diagnosis of lung carcinoma. Grossly, a white tumor of 1 × 0.8 cm was recognized in the lung. Microscopically, the tumor was connected to the pulmonary arteries. The tumor was composed of mature smooth muscles. Small pulmonary arteries are embedded in the tumor. No lymphatics were seen. Immunohistochemically, the tumor cells were poisitive for alpha-smooth muscle actin, vimentin and Ki-67 (labeling 2%). However, they were negative for cytokeratin (CK) AE1/3, CK CAM5.2, desmin, S100 protein, p53, CD34, KIT, HMB45, estrogen receptor, progesterone receptor, and myoglobin. A pathological diagnosis of primary vascular leiomyoma arising from the smooth muscle of pulmonary artery was made. The patient is now free from tumor, and is now alive 10 year after the operation.


Expression of MUC apomucins has rarely been investigated in the signet-ring cell carcinoma (SRCC) of the stomach and colorectum. The author examined immunohistochemically the expression status of MUC1, MUC2, MUC5AC, and MUC6 in 30 cases of gastric SRCC and 12 cases of colorectal SRCC. The normal distribution of these MUC apomucins was also examined in the non-tumorous parts of the stomach and colorectum. In normal tissues, the stomach epithelial cells consistently expressed MUC2, MUC5AC, MUC6, but consistently not MUC1. In colorectum, cryptal epithelial cells consistently expressed MUC2, but consistently not MUC1, MUC5AC, and MUC6. The expression pattern of the gastric SRCC was as follows: MUC1, 3/30 (10%); MUC2, 4/30 (13%); MUC5AC, 20/30 (67%), and MUC6 21/30 (70%). The expression pattern of the colorectal SRCC was as follows: MUC1, 5/12 (42%); MUC2, 11/12 (92%); MUC5AC, 4/12 (33%); and MUC6, 0/12 (0%). Significant differences (p<0.05) were found in the expression of MUC1 (stomach SRCC 10% vs colorectal SRCC 42%), MUC2 (13% vs 92%), MUC5AC (67% vs 33%), and MUC6 (70% vs 0%). Thus, there was a significant tendency that primary gastric SRCC express MUC5AC and MUC6 but not MUC1 and MUC2, while primary colorectal SRCC express MUC1, MUC2 and MUC5A, but not MUC6. These different expressions of these MUC apomucins in gastric and colorectal SRCC seem useful to determine the primary site of metastatic SRCC and for differential diagnosis of SRCC of other sites. In the gastric SRCC, the up-regulation of MUC1 and the down-regulation of MUC2, MUC5AC and MUC6 appear to be associated with carcinogenesis, malignant potential, progression, and clinical behaviors in gastric SRCC. In the colorectal SRCC, the up-regulation of MUC1 and MUC5AC may be associated with carcinogenesis, malignant potential, progression, and clinical behaviors in colorectal SRCC. A comparative review of the present SRCC and presently reported ordinary adenocarcinoma and SRCC cases of the stomach and colorectum was performed.


There have no comprehensive immunohistochemical studies of primary signet ring cell carcinoma (SRCC) in the stomach and colorectum. The author examined the expression of nine common antigens (EMA, CEA, CA19-9, CDX-2, p53, Ki-67 antigen, TTF-1, vimentin, and p63) in the non-tumorous normal epithelium of the stomach and colorectum and in 42 cases of primary SRCC of the stomach (30 cases) and colorectum (12 cases). The normal epithelium of the stomach and colon consistently (100%) expressed EMA, CEA, CA19-9, CDX-2, and Ki-67 (labeling <15%). Normal epithelium of these locations never expressed p53, TTF-1, vimentin, and p63. In the primary gastric SRCC, the expression percentage of EMA was 57% (17/30), CEA 100% (30/30), CA19-9 100% (30/30), CDX-2 43% (13/30), p53 83% (25/30), Ki-67 100% (30/30) (labeling index= 36 ± 23 %), TTF-1 0% (0/30), vimentin 0% (0/30), and p63 0% (0/30). In primary colorectal SRCC, the expression percentage of EMA was 25% (3/12), CEA 100% (12/12), CA19-9 100% (12/12), CDX-2 93% (28/30), p53 75% (9/12), Ki-67 100% (30/30) (labeling index= 47% ± 26 %), TTF-1 0% (0/12), vimentin 0% (0/12), and p63 0% (0/12). A comparative statistical analysis showed significant difference in EMA (gastric SRCC 57% vs colorectal SRCC 25%) and CDX-2 (43% vs 93%). There were no significant differences in the other seven antigens' expression between primary gastric SRCC and primary colorectal SRCC. These findings provide much knowledge of primary SRCC of the stomach and colorectum. The data indicated primary gastric SRCC frequently express EMA but not CDX-2 whereas primary colorectal SRCC frequently express CDX-2 but not EMA. These findings also suggest that EMA and CDX-2 are down-regulated during the gastric SRCC carcinogenesis. This down regulations may be associated with the malignant transformation of gastric SRCC. The data of colorectal SRCC suggest EMA is markedly down-regulated and also suggest that this EMA down-regulation may be associated with the carcinogenesis of colorectal SRCC. The expression pattern of EMA and CDX-2 may be useful in differential diagnosis between primary gastric SRCC and primary colorectal SRCC in the metastatic sites of SRCC.


Terada T.,Shizuoka City Shimizu Hospital
International Journal of Clinical and Experimental Pathology | Year: 2012

There are few comprehensive studies of small intestinal malignancies. The author retrospectively reviewed 1,312 archival pathologic specimens of the small intestine in the last 10 years in our pathologic laboratory in search for malignant tumors of the small intestine. There were 22 cases (1.7%) of primary adenocarcinoma, 3 cases (0.2%) of primary squamous cell carcinoma, 6 cases (0.5%) of metastatic carcinoma, 6 cases (0.5%) of malignant lymphoma, 3 cases (0.2%) of carcinoid tumor, and 1 case (0.08%) of gastrointestinal stromal tumor (GIST). Of the 25 cases of primary adenocarcinoma and squamous cell carcinoma, 24 cases were located in the duodenum and 1 case in the ileum. The 22 cases of adenocarcinoma were classified into 7 well differentiated, 7 moderately differentiated, and 8 poorly differentiated adenocarcinomas. All the three squamous cell carcinomas were moderately differentiated ones with keratinization and intercellular bridges. In the 25 cases of carcinoma, immunoreactive p53 protein was present in 23 cases, and the Ki-67 labeling ranged from 40% to 95% with a mean of 76%. In the 6 cases of metastatic adenocarcinoma, the origin was ovary in 1 case, pancreas in 2 cases, gall bladder in 1 case, lung in 1 case, and colon in 1 case. In the 6 cases of lymphoma, 4 cases were diffuse large B-cell lymphomas and 2 cases were peripheral T-cell lymphomas. In the 3 cases of carcinoid tumor, all were typical carcinoids and immunohistochemically positive for at least one of neuroendocrine markers (chromogranin, synaptophysin, neuron specific enolase, and CD56). In the 1 case of GIST, the cell type is spindle and GIST cells were immunohistochemically positive for KIT and CD34. The histological risk was intermediate. Forty-one cases of small intestinal malignancies were reviewed histopathologically.


Terada T.,Shizuoka City Shimizu Hospital
International Journal of Clinical and Experimental Pathology | Year: 2013

The frequency of gall bladder lesions in cholecystectomies is not clear. The purpose of the present study is to report the morphologies and frequency of gall bladder diseases and lesions of 540 cholecystectomies in the last 10 years in our pathology laboratory. The age of patients ranged from 18 years to 93 years with a mean of 64.75 ±14.43 years. Male to female ratio was 213:327. Of these, 518 cases (96%) had gall stones. Eight (1.5%) were acute cholecystitis, 508 (94.1%) were chronic cholecystitis, 12 (2.2%) were adenocarcinomas, 1 (0.2%) was cystadenocarcinoma, and 11 (2.0%) were normal gall bladders. The frequency of histological lesions were as follows: acute gangrenous inflammation (8 cases, 1.5%), Rokitansky-Aschoff sinuses (RAS) (351 cases, 65%), microliths or inspissated bile in RAS (108 cases, 20%), adenomyomatous changes (16 cases, 3.0 %), focal abscess formations (12 cases, 2.2%), focal xanthogranulomatous changes (15 cases, 2.8%), mucosal ulcers (61 cases, 11.3%), cholesterosis (62 cases, 11%), cholesterol polyp (32 cases, 6%), pyloric gland metaplasia (292 cases, 54%), adenoma (7 cases, 1.3%), xanthogranulomatous cholecystitis (5 cases, 1%), invasive adenocarcinoma (12 cases, 2.2%), and cystadenocarcinoma (1 cases, 0.2%). In adenomyomatous changes, the epithelial proliferation was florid in a few cases, and no perineural invasions were seen. In pyloric gland metaplasia, no perineural invasions were recognized. All the 7 cases of adenoma were of intestinal type. In the 12 adenocarcinoma cases, one case arose in RAS without mucosal involvement, and 9 were tubular adenocarcinomas and 3 were papillary adenocarcinomas and 1 was mucinous adenocarcinoma. In the present series, there were no cases of heterotipc tissue, intestinal metaplasia, intraepithelial neoplasm, and other malignancies. These data may provide basic knowledge of the gall bladder pathologies.


Terada T.,Shizuoka City Shimizu Hospital
International Journal of Clinical and Experimental Pathology | Year: 2012

KIT and PDGFRA in small cell lung carcinoma (SCLC) have been rarely examined in Japanese. The author investigated protein expression of KIT and PDGFRA in 54 Japanese cases of small cell lung carcinoma by immunohistochemistry, and gene mutations of KIT and PDGFRA in 20 Japanese cases of small cell lung carcinoma by the PCRdirect sequencing method. The molecular genetic analysis showed no mutations of KIT (exons 9, 11, 13, and 17) and PDGFRA (exons 12 and 18) genes in all 20 cases. KIT protein expression was recognized in all cases (100%). Membranous KIT expression was strong in 35 cases, moderate in 7 cases and weak in 12 cases. PDGFRA protein expression was noted in 35 cases (65%); the membranous expression was strong in 2 cases, moderate in 16 cases, and weak in 17 cases. The overall median survival was 13 months. There was no significant difference in the survival between KIT strongly positive cases (median, 12 months) and KIT moderately or weakly positive cases (median, 11 months). Likewise, there was no significant difference in the survival between PDGFRA-positive cases (median, 11 months) and PDGFRA-negative cases (median, 12 months). The protein expressions of KIT and PDGFRA did not correlate with gender, smoking, and disease stage. These findings suggest, in Japanese population, that mutations of KIT and PDGFRA were absent in small cell lung carcinoma of Japan, that KIT protein expression is present in 100%, that PDGFRA expression is present in 65%, and that KIT and PDGFRA protein expressions do not correlate with survival, gender, smoking, and disease stage.

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