Interobserver variability in histologic recognition, interpretation of KIT immunostaining, and determining MIB-1 labeling indices in gastrointestinal stromal tumors and other spindle cell tumors of the gastrointestinal tract.

The authors studied the concordance among seven pathologists for the histologic diagnosis, interpretation of KIT immunostaining, and determining MIB-1 labeling indices (LI) in 80 adult patients with primary spindle cell tumors, mainly of the gastrointestinal tract, mesentery, retroperitoneum, and pelvis, based on the review of tissue sections using an immunohistochemical panel of antibodies for KIT/CD117, CD34, desmin, smooth muscle actin (SMA), and S-100 protein. Tumors included 30 gastrointestinal stromal tumors (GISTs), 10 leiomyomas, 10 leiomyosarcomas, 10 schwannomas, 10 solitary fibrous tumors, and 10 desmoid-type fibromatoses. The overall concordance with the original diagnosis of each histologic type was 97.9%, the kappa value ranging from 0.95 to 1.00 (mean 0.97), indicating a perfect agreement. The overall interlaboratory concordance with the original interpretation of KIT immunostaining was 91.3%, the kappa value ranging from 0.77 to 0.90 (mean 0.86). The overall interlaboratory concordance with the original interpretation of KIT immunostaining was 91.9%, the kappa value ranging from 0.72 to 0.93 (mean 0.85). The overall concordance for determining MIB-1 LI was 90% with the original evaluation, and the overall kappa value ranged from 0.62 to 0.86 (mean 0.77). These results indicate that it is possible to reliably diagnose GIST and other spindle cell tumors of the gastrointestinal tract with the use of an immunohistochemical panel of antibodies for KIT, CD34, desmin, SMA, and S-100 protein. Although there is clearly unavoidable inter-observer and interlaboratory variability in the interpretation of KIT immunostained sections and interobserver variability in the determination of MIB-1 LI, the concordance between observes is very acceptable, and in most instances such variability can be eliminated by careful reviewing of the hematoxylin and eosin and immunostained sections.     

Vertical and horizontal growth features of superficial esophageal squamous cell carcinomas: histopathological evaluation of endoscopically resected specimens

Endoscopic mucosal resection (EMR) has been performed for intramucosal carcinomas with excellent results. To evaluate invasion depth of superficial esophageal squamous cell carcinomas (SESCCs) accurately, it is important to elucidate vertical and horizontal growth features. Using 179 specimens of SESCC taken by EMR, various factors associated with vertical and horizontal growth were examined pathologically to determine which were correlated with invasion depth, classified for this purpose into four levels, m1, m2, m3, and sm. Maximum tumor diameter, including high-grade intraepithelial neoplasia, differed between m1 and m2 cases and for invasive lesions between m2 and m3. Maximum tumor thickness varied between m1 and m2, m2 and m3, and m3 and sm. Multivariate analysis showed tumor thickness and diameter of invasion to be correlated with submucosal invasion. Tumor thickness and depth of the depressed lesions were correlated in depressed/flat type cases. In elevated type cases the thickness of the tumor did not differentiate between m3 and sm. Shape of the elevated lesion also influenced the invasion depth. Frequency of infiltrating type tumors, composed of irregular and small invading nests, was higher with sm than m3. To differentiate m3 and sm tumor the classification of gross type, thickness, depth of depressed lesions, shape of elevated lesions, and invasion patterns should all be evaluated.     

Pseudomyxoma retroperitonei

We report a rare case of pseudomyxoma retroperitonei in a 58-year-old woman with a past history of severe appendicitis. The imaging showed a multicystic mass similar to pseudomyxoma peritonei, but the tumor was located in the retroperitoneal space. Received: 20 October 1997; Revision received: 10 February 1998; Accepted: 2 March 1998     

Characteristics of intramural metastasis in gastric cancer

Background

Intramural metastasis (IM) in gastric cancer is rare. However, it often occurs with esophageal squamous cell carcinoma and has been reported to have a poor prognosis.

Methods

In 4,714 cases of gastric cancer that underwent gastrectomy, the clinicopathological features and postoperative prognoses of 29 cases with IM were evaluated and compared with 2,770 cases of advanced gastric cancer without IM.

Results

Of the 4,714 cases, 29 (0.6 %) were histopathologically diagnosed with gastric cancer with IM. There were significant differences in the number of lymph node metastases, capillary invasion, and stage grouping between cases with IM and advanced gastric cancer without IM. Metastasis size was approximately within 2 cm, and many metastases occurred within 2 cm of the primary lesion. Multiple metastases were observed in 38 % of cases and occurred mainly in the submucosa and muscularis propria. IM was detected preoperatively in 17.2 % of cases and was present equally on both sides of the primary lesion. Nine cases had IM outside the stomach. The median survival time with IM was significantly less than in cases of advanced gastric cancer without IM (p < 0.0001). A subgroup of cases with IM within 1 cm of the primary lesion had a relatively favorable prognosis.

Conclusions

The presence of IM is thought to be one of the most important prognostic factors in gastric cancer. Aggressive resection is recommended to increase long-term survival if curative resection is possible.     

Role of interleukin-18 in intrahepatic inflammatory cell recruitment in acute liver injury

Although the innate immune system has been demonstrated to play important roles as the first line of defense against various infections, little is known about the interactions between intrahepatic inflammatory cells and the cytokine network in the liver. Here, we examined the role of IL-18 in IHL recruitment in acute liver injury. C57BL/6 mice were injected with an αCD40 mAb, and their serum IL-18 levels were observed to increase, with subsequent recruitment of IHLs into the liver. NKT cells were involved in this liver injury, as the serum ALT levels were reduced in NKT KO mice through the suppression of macrophage and monocyte migration and cytokine production. In contrast, depletion of neutrophils exacerbated the liver injury associated with high levels of TNF-α and IL-18 and increased numbers of macrophages and monocytes. Treatment with a neutralizing antibody against IL-18 reduced the serum ALT levels and inflammatory cell accumulation in the liver. Finally, additional administration of rIL-18 with αCD40 injection caused severe liver injury with increased IFN-γ production by NK cells. In conclusion, these findings demonstrate that IL-18 modulates liver inflammation by the recruitment of inflammatory cells, including NKT cells, macrophages, monocytes, and neutrophils.     

Serum IgG4-negative autoimmune pancreatitis

Background  

Autoimmune pancreatitis (AIP) is considered to be a pancreatic lesion of IgG4-related systemic disease, but about 20% of AIP patients do not have elevated serum IgG4 levels. This study aimed to clarify the pathophysiology of AIP patients without elevated serum IgG4 levels.