Primary multiple extragastrointestinal stromal tumors of the omentum with different mutations of c-kit gene

The author reports a very rare case of sporadic primary multiple extragastrointestinal stromal tumors (EGISTs) of the omentum associated with different mutations of the exon 11 of the c-kit gene in a 75-year-old man with gastric cancer. During an operation for the cancer, two solid tumors (10 mm and 8 mm) were found in the omentum. Both tumors consisted of cellular spindle cells. Mitotic figures were two and three per 50 high power fields. The tumor cells were positive for KIT, CD34 and vimentin, but negative for desmin, S100 protein, α-smooth muscle actin and p53 protein. Ki67 labeling was 2% and 3%. The larger EGIST showed a deletion of codons 552-558 of exon 11 of the c-kit gene, while the smaller EGIST had a point mutation at codon 559 (GTT←GAT) in exon 11 of the c-kit gene. Exons 9, 13, and 17 of the c-kit gene, and exons 12 and 18 of the platelet derived growth factor receptor α genes showed no mutations. The case shows that sporadic multiple EGISTs can occur in the omentum.

Simultaneous large cell neuroendocrine carcinoma and adenocarcinoma of the stomach

A large cell neuroendocrine carcinoma(LCNEC) of the stomach is very rare.A 76-year-old Japanese man was admitted to our hospital because of epigastralgia and nausea.Endoscopy revealed 2 large tumors in the stomach.He did not have multiple endocrine neoplasia typeⅠor Zollinger-Ellison syndrome.Imaging modalities,including computed tomography and magnetic resonance imaging,revealed no other tumors.Gastrectomy,cholecystectomy,and lymph node dissection were performed.The resected stomach had 2 tumors:one was an antral ulcerated type 3 tumor measuring 5 cm x 5 cm,and the other was a polypoid type 1 tumor measuring 6 cm x 6 cm x 3 cm in the fundus.Microscopically,the antral ulcerated tumor was a well differentiated adenocarcinoma with deep invasion.The fundus polypoid tumor was a LCNEC,being composed of malignant large cells arranged in trabecular and nested patterns.The tumor cells were large and the nuclei were vesicular.Nucleoli were frequently present,and there were many mitotic figures,apoptotic bodies,and necrotic areas.Much lymphovascular permeation was seen.Seven out of 29 dissected lymph nodes showed metastatic foci;6 were from the LCNEC and 1 from theadenocarcinoma.Many intravascular tumor emboli of LCNEC were seen in the peritoneum around the lymph nodes.Mucins were present in the adenocarcinoma but not in the LCNEC.Immunohistochemically,the LCNEC tumor cells were positive for pancytokeratins,synaptophysin(50%positive) ,chromogranin A(10% positive) ,Ki-67(90%labeled) ,and platelet-derived growth factor-α(80%positive) .They were negative for KIT,p53,CD56,and neuron-specific enolase.The non-cancerous stomach showed a normal number of endocrine cells.The patient is now treated with adjuvant chemotherapy.

Esophageal combined carcinomas:Immunohoistochemical and molecular genetic studies

Primary esophageal combined carcinoma is very rare.The authors herein report 2 cases.Case 1 was a combined squamous cell carcinoma and small cell carcinoma,and case 2 was a combined squamous cell carcinoma,adenocarcinoma,and small cell carcinoma.Case 1 was a 67-year-old man with complaints of dysphagia.Endoscopic examination revealed an ulcerated tumor in the middle esophagus,and 6 biopsies were obtained.All 6 biopsies revealed a mixture of squamous cell carcinoma and small cell carcinoma.Both elements were positive for cytokeratin,epithelial membrane antigen,and p53 protein,and had high Ki-67 labeling.The small cell carcinoma element was positive for synaptophysin,CD56,KIT,and platelet-derived growth factor-α(PDG-FRA),while the squamous cell carcinoma element was not.Genetically,no mutations of KIT and PDGFRA were recognized.The patient died of systemic carcinomatosis 15 mo after presentation.Case 2 was a 74-year-old man presenting with dysplasia.Endoscopy revealed a polypoid tumor in the distal esophagus.Seven biopsies were taken,and 6 showed a mixture of squamous cell carcinoma,small cell carcinoma,and adenocarcinoma.The 3 elements were positive for cytokeratins,epithelial membrane antigen,and p53 protein,and had high Ki-67 labeling.The adenocarcinoma element was positive for mucins.The small cell carcinoma element was positive for CD56,synaptophysin,KIT,and PDGFRA,but the other elements were not.Mutations of KIT and PDGFRA were not recognized.The patient died of systemic carcinomatosis 7 mo after presentation.These combined carcinomas may arise from enterochromaffin cells or totipotential stem cell in the esophagus or transdifferentiation of one element to another.A review of the literature was performed.

Amelanotic malignant melanoma of the esophagus:Report of two cases with immunohistochemical and molecular genetic study of KIT and PDGFRA

The author reports herein two cases of amelanotic malignant melanoma of the esophagus.Case 1 is an 87-year-old woman who was admitted to our hospital because of nausea and vomiting.Endoscopic examination revealed an ulcerated tumor of the distal esophagus,and a biopsy was taken.The biopsy showed malignant polygonal and spindle cells.No melanin pigment was recognized.Immunohistochemically,the tumor cells were positive for melanosome(HMB45),S100 protein,KIT and Platelet derived growth factor receptor-α(PDG-FRA).The patient was treated by chemotherapy and radiation,but died of systemic metastasis 12 mo after the presentation.Case 2 is a 56-year-old man presenting with dysphagia.Endoscopic examination revealed a polypoid tumor in the middle esophagus,and a biopsy was obtained.The biopsy showed malignant spindle cells without melanin pigment.Immunohistochemically,the tumor cells were positively labeled for melanosome,S100 protein,KIT and PDGFRA.The patient refused operation,and was treated by palliative chemotherapy and radiation.He died of metastasis 7 mo after the admission.In both cases,molecular genetic analyses of KIT gene(exons 9,11,13 and 17) and PDGFRA gene(exons 12 and 18) were performed by the PCR direct sequencing method,which showed no mutations of KIT and PDGFRA genes.This is the first report of esophageal malignant melanoma with an examination of the expression of KIT and PDGFRA and the mutational status of KIT and PDGFRA genes.

Schistosomal appendicitis:Incidence in Japan and a case report

Schistosomal appendicitis is very rare in developed countries like the USA,Europe,and Japan.The author reviewed 311 pathologic archival specimens of vermiform appendix over the past 10 years.One case of schistosomal appendicitis was recognized.Therefore,the incidence of this disease was 0.32% in all appendices surgically resected in our hospital.The patient was a 41-year-old woman presenting with lower abdominal pain.She was a sailor traveling to many countries including endemic areas.Physical examination,laboratory data,and imaging modalities suggested an acute appendicitis,and appendectomy was performed under the diagnosis of ordinary appendicitis.Histologically,numerous schistosomal eggs were present in the vasculatures throughout the appendiceal walls.Some of the eggs were calcified.Stromal foreign body reaction was also recognized.The appendicitis was phlegmonous consisting of severe infiltrations of neutrophils and eosinophils.Acute serositis was also noted.Examination of feces revealed numerous eggs of Schistosoma mansoni.Clinicians should be aware of schistosomal appendicitis.

电脑数据库中10,000例连续胃组织标本的组织病理学研究:(2)恶性病变

通过电脑数据库,作者对一家日本大型医院病理实验室2002-2013年间的10,000例连续胃组织标本进行组织病理学分析。所有组织切片被回顾性观察,这10,000例胃组织标本中良性病变8579例,恶性病变1421例。恶性病变中胃癌1342例(94.4%),胃肠间质瘤(GIST)34例(2.4%),黏膜相关淋巴组织(MALT)淋巴瘤25例(1.8%),非霍奇金恶性淋巴瘤19例(1.3%),转移癌1例(0.1%)。在1342例胃癌中,管状腺癌755例,乳头状腺癌176例,黏液腺癌147例,印戒细胞癌145例,低/未分化腺癌114例,腺鳞癌4例,转移性肺小细胞癌1例。在手术切除标本中,早期胃癌258例,进展期胃癌521例。在34例GIST中,2例为上皮细胞型,32例为梭形细胞型;GIST大小为1-15 cm,平均5.6 cm;KIT(CD117)表达均为阳性,CD34阳性31例,desmin阳性2例,S100阳性4例。6例GIST进行了基因检测,均显示KIT和/或PDGFRA点突变。在25例MALT淋巴瘤中均可见到中心细胞样细胞和淋巴上皮病变;92%的病变可发现幽门螺杆菌感染。在19例非霍奇金淋巴瘤中,17例为弥漫性大B细胞淋巴瘤,1例为外周T细胞淋巴瘤,1例为NK细胞淋巴瘤。

Histopathological study using computer database of 10000 consecutive gastric specimens:(1)benign conditions

Using a computer database,the author investigated the histopathology of 10000 consecutive gastric specimens,taken in the last 12 years(2002-2013)at the pathology laboratory of a Japanese hospital.Re-observation of the already examined histological sections was done when the histological diagnosis and findings on the computer data base were not very obvious.The gastric specimens were identified as 8579 benign conditions and 1421 malignant lesions.The 8579 benign conditions were comprised almost normal stomach in 74 cases(0.9%),chronic gastritis in 4374(51.0%),benign gastric peptic ulcer in 2195(25.6%),foveolar hyperplastic polyp in 1004(11.7%),fundic gland polyp in 421(4.9%),adenoma in 487(5.6%),heterotopic pancreas in 9(0.1%),pancreatic acinar metaplasia(PAM)in 8(0.1%),and amyloidosis in 7(0.1%).Chronic gastritis showed lymphocytic infiltration and frequently showed erosions and intestinal metaplasia.Gastric peptic ulcer showed exudate,necrosis,active inflammation,and regenerative atypia of the epithelium.Foveolar hyperplastic polyp revealed 23 malignant changes and frequently showed dysplastic glands and intestinal metaplasia.Fundic gland polyp demonstrated cystic dilations of fundic gland ducts.Gastric adenoma showed adenomatous proliferation in the superficial mucosa and cystic dilation of the epitheliumunder the adenoma.Heterotopic pancreas was located in the submucosa and consisted of acinar cells,ducts,and occasionally islets.PAM was a tiny lesion in the mucosa and consisted of only pancreatic acinar cells.Amyloidosis was primary amyloidosis with positive reaction with Congo-red stain.