Mai Iwaya

Giant cauda equina schwannoma

Schwannoma is a benign tumor that often grows from the spinal root. A 42-year-old woman first experienced lumbar pain and left-side ischiadic neuralgia at the age of 40 years. Her symptoms progressed gradually; she developed dysesthesia of the left leg and urinary incontinence 6 months before admission. Thereafter, she had gait disturbance, lumbago and pain in both legs. On admission, she had flaccid paraplegia and sensory loss below Th10. Magnetic resonance imaging showed a large tumor occupying the whole lumbar and upper sacral canal associated with thoracolumbar cord syrinx (Fig. 1a,b). The tumor was lobularly enhanced (Fig. 1c,d). A restricted biopsy of the tumor led to the diagnosis of schwannoma (Fig. 1e,f). Because schwannoma grows along with the nerve root from the intradural space to outside of the spinal canal, it sometimes presents as a dumbbell-like appearance. The tumor also grows

A case of primary signet-ring cell/histiocytoid carcinoma of the eyelid: immunohistochemical comparison with the normal sweat gland and review of the literature.

Abstract:Primary signet-ring cell/histiocytoid carcinomas of the eyelid are extremely rare tumors considered to originate from sweat glands. Here, we report the case of a 72-year-old man diagnosed with primary signet-ring cell/histiocytoid carcinoma of the eyelid and present immunohistochemical analyses of the eyelid apocrine gland (Moll gland) and apocrine and eccrine sweat glands of perineum and axilla. Widespread infiltration of tumor cells with signet-ring cell or histiocytoid appearance was observed in his left eyelid, orbit, and periocular lesion. Tumor cells expressed mucins and showed immunoreactivity that was similar to that of the Moll gland: MUC6(+), GlcNAc&agr;1→4Gal→R(−), MUC2(−), MUC5AC(−), GCDFP15(+), CD15(+), S100(−), CK7(+), CK20(-), ER(+), PgR (+), HER2(−), E-cadherin(+), p63(−), PSA(−), and TTF-1(−). The tumor cells differed from those of perineal and axillary apocrine and eccrine sweat glands, which were MUC6(−). The Moll gland was ER(−) and PgR(−), whereas perineal and axillar apocrine sweat glands were ER(+) and PgR(+), and perineal and axillary eccrine sweat glands were ER(+) and PgR(−). The tumor showed characteristics similar to that of the eyelid Moll gland, which is demonstrated to be an apocrine gland with a protein expression distinct from that of other apocrine glands. MUC6 and GCDFP15 expression are useful in identifying the Moll gland immunophenotype and GCDFP15, ER and PgR expression are useful in distinguishing primary eyelid signet-ring/histocytoid carcinoma from gastrointestinal malignancies.

Pulmonary Tumor Thrombotic Microangiopathy Caused by Urothelial Carcinoma Expressing Vascular Endothelial Growth Factor, Platelet-derived Growth Factor, and Osteopontin

Pulmonary tumor thrombotic microangiopathy (PTTM) is a fatal cancer-related pulmonary complication. It is generally caused by gastric adenocarcinoma, and several molecules produced by tumor cells are reported to play important roles in its pathogenesis. We herein report an autopsy case of PTTM caused by urothelial carcinoma. Vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and osteopontin were found to be expressed in both the primary tumor cells and metastatic cells in the PTTM lesions. These findings implicate the possible involvement of VEGF, PDGF, and osteopontin in the pathogenesis of PTTM caused by urothelial carcinoma.

A case of simultaneous esophageal squamous cell carcinoma and Barrett’s adenocarcinoma

A 77-year-old male with a long history of alcohol consumption and smoking was admitted for hoarseness and dysphagia. Computed tomography revealed thickening of the middle intrathoracic esophageal wall and multiple mediastinal lymph node swellings. Esophagogastroduodenoscopic examination disclosed an advanced-stage squamous cell carcinoma lesion in the middle intrathoracic esophagus with synchronous early stage Barrett’s adenocarcinoma. The patient underwent endoscopic submucosal dissection for the adenocarcinoma followed by chemoradiation therapy for the squamous cell carcinoma. In spite of their common risk factors, the simultaneous manifestation of esophageal squamous cell carcinoma and Barrett’s adenocarcinoma is extremely rare and requires further study.

Principal cells in gastric neoplasia of fundic gland (chief cell predominant) type show characteristics of immature chief cells.

To the Editor: In the normal gastric fundic mucosa, the digestive-enzymes secreting chief cells differentiate from mucous neck cells via the transdifferentiation route. Mucous neck cells possess MUC6 bearing GlcNAcα1→4Galβ→R structures specifically recognize by paradoxical Concanavalin A staining and monoclonal antibody HIK1083 (HIK1083 mAb), TFF2, which is a lectin binding with high specificity to O-linked α1,4-GlcNAc-capped hexasaccharides on gastric mucin, and pepsinogen I. Chief cells tend to lose MUC6 and TFF2

Helicobacter pylori -negative Differentiated Adenocarcinoma of the Stomach

A 58-year-old Japanese man was diagnosed with differentiated adenocarcinoma of the stomach. Histological findings of the resected specimen revealed well- to moderately-differentiated tubular adenocarcinoma (tub1, tub2), 13 mm in diameter, which invaded into the submucosa (SM1, 300 μm) and lymphovascular lumen (ly1). Serum antibody against Helicobacter pylori (Hp) and the (13)C-urea breath test were negative, and there were no atrophic changes in the tumor-adjacent mucosa. The immunohistochemical analysis showed that gastric mucin (MUC5AC) was strongly positive and intestinal mucin (MUC2) was weakly and partially positive. According to these results, the final diagnosis of Hp-negative well-differentiated early gastric cancer was made.

Distribution of Lgr5-positive cancer cells in intramucosal gastric signet-ring cell carcinoma

Leucine‐rich repeat‐containing G‐protein‐coupled receptor 5 (Lgr5) is a putative intestinal stem cell marker that is also expressed in various tumors. To analyze its pathological characteristics in mucosal gastric signet‐ring cell carcinoma (SRCC), we investigated Lgr5 expression in 35 intramucosal gastric SRCC patients using RNAscope, a newly developed RNA in situ hybridization technique. Lgr5 expression in individual tumor cells was scored semi‐quantitatively from 0 to 400. Ki67 was also examined by immunohistochemistry, with a linear arrangement of Ki67‐expressing cells present in 20 of 35 cases. This area of Ki67‐expressing cells was topographically divided into upper, middle, and lower regions. All cases with linear Ki67 expression patterns also had Lgr5‐positive cells arranged in a linear fashion in the lower area—which was distinct from the area of high Ki67 expression. The rate of Ki67 positivity in Lgr5‐positive cells was significantly lower than that of Lgr5‐negative cells in areas of high Ki67 expression. In intramucosal SRCC, the low mitotic activity of Lgr5‐positive cells suggests that they may represent cancer stem cells as seen in other types of stomach carcinomas. Intramucosal SRCC may therefore contain stem cells expressing Lgr5 in the lower area of the lamina propria, akin to normal gastric pyloric mucosa.

Insulin-Like Growth Factor II mRNA-Binding Protein 3 (IMP3) as a Useful Immunohistochemical Marker for the Diagnosis of Adenocarcinoma of Small Intestine.

The biological characteristics and roles of insulin-like growth factor II mRNA-binding protein 3 protein (IMP3) expression in small-intestinal adenocarcinoma were investigated. The value of IMP3 immunostaining in the diagnosis of small-intestinal epithelial lesions was also evaluated. Immunohistochemical expression of IMP3 in normal small-intestinal mucosa adjacent to adenoma and adenocarcinoma lesions, and inflamed duodenal and ileal mucosa was analyzed. Samples assessed were: duodenal ulcer (n=6), Crohn’s disease (n=5), low-grade small-intestinal adenoma (n=10), high-grade small-intestinal adenoma (n=13), small-intestinal adenocarcinoma (n=23), lymph node metastases (LNM; n=7), and preoperative biopsies of small-intestinal adenocarcinoma (n=6). Immunohistochemical expression of Ki-67 and p53 was also analyzed in adenoma and adenocarcinoma samples. IMP3 was not expressed in normal epithelium, but weakly expressed in reparative epithelium. Meanwhile, increased IMP3 expression was associated with a higher degree of dysplasia in adenomas, higher T classification, LNM, Ki-67 positivity, histological differentiation, and lower 5-year disease-free survival, but not p53 expression in adenocarcinoma. IMP3 expression appears to be a late event in the small-intestinal carcinogenesis. Assessing the IMP3 staining pattern can be useful in the diagnosis of small-intestinal epithelial lesions when used in conjunction with other histological criteria.

AComparative Immunohistochemical Study of Anal Canal Epithelium in Humans and Swine, Focusing on the Anal Transitional Zone Epithelium and the Anal Glands: ANAL CANAL EPITHELIUM IN HUMAN AND SWINE

To better understand the cellular origins and differentiation of anal canal epithelial neoplasms, the immunohistochemical profiles of the anal canal epithelium in humans and swine were evaluated. Formalin‐fixed tissue sections were immunostained for mucin (MUC: MUC2, MUC5AC, MUC5B), desmoglein 3 (DGS3), p63, CDX2, SOX2, and α‐smooth muscle actin (α‐SMA). The anal transitional zone (ATZ) epithelium covered the anal sinus and consisted of a stratified epithelium with mucous cells interspersed within the surface lining. Anal glands opened into the anal sinus. Ducts and acini of intraepithelial or periepithelial mucous type were the main structures of human anal glands, whereas those of swine were compound tubuloacinar mixed glands. Distal to the ATZ epithelium, non‐keratinized stratified squamous epithelium merged with the keratinized stratified squamous epithelium of the perianal skin. MUC5AC expression predominated over MUC5B expression in the ATZ epithelium, while MUC5B expression was higher in the anal glands. SOX2 was positive in the ATZ epithelium, anal glands, and squamous epithelium except in the perianal skin. In humans, DGS3 was expressed in the ATZ epithelium, anal gland ducts, and squamous epithelium. p63 was detected in the ATZ epithelium, anal glands, and squamous epithelium. Myoepithelial cells positive for α‐SMA and p63 were present in the anal glands of swine. Colorectal columnar cells were MUC5B+/MUC2+/CDX2+/MUC5AC−/SOX2−. The ATZ epithelium seems to be a distinctive epithelium, with morphological and functional features allowing smooth defecation. The MUC5AC+/SOX2+/MUC2−/CDX2− profile of the ATZ epithelium and anal glands is a useful feature for diagnosing adenocarcinoma arising from these regions. Anat Rec, 301:796–805, 2018.