Histopathological study using computer database of 10 000 consecutive gastric specimens: (2) malignant lesions

Using a computer database, the author investigated the histopathology of 10 000 consecutive gastric specimens collected in the last 12 years 2002–2013 at his pathology laboratory in a relatively large hospital in Japan. Examination of histological sections was done when appropriate. The gastric specimens were made up of 8579 benign conditions and 1421 malignant lesions. The latter comprised gastric carcinoma in 1342 cases (94.4%), gastrointestinal stromal tumor (GIST) in 34 (2.4%), mucosal-associated lymphoid tissue (MALT) lymphoma in 25 (1.8%), non-Hodgkin's malignant lymphoma in 19 (1.3%), and metastatic carcinoma in 1 case (0.1%). Of the 1342 cases of gastric carcinoma, the histological type was as follows: tubular adenocarcinoma in 755 cases, papillary adenocarcinoma in 176, mucinous adenocarcinoma in 147, signet ring cell carcinoma in 145, poorly differentiated adenocarcinoma in 114, adenosquamous carcinoma in 4, and metastatic small cell carcinoma from the lung in 1. In surgically resected cases, the number of early gastric carcinomas was 258 and of advanced carcinoma, 521 cases. In GIST (n = 34), there were 2 cases of the epithelioid type and 32 of the spindle cell type. The size of GIST ranged from 1–15 cm, with a mean of 5.6 cm. KIT (CD117) was positive in 34/34 cases, CD34 in 31/34, desmin 2/34, and S100 4/34. A genetic analysis was performed in 6 cases of GIST, all of which showed point mutation of KIT and/or PDGFRA genes. In MALT lymphoma (n = 25), centrocyte-like cells and lymphoepithelial lesions were seen in every case. Helicobactor pylori infection was noted in 92%. In non-Hodgkin's lymphoma (n = 19), 17 cases were of diffuse large B-cell lymphoma, and 1 was peripheral T-cell lymphoma, while 1 was NK-cell lymphoma.


Materials and methods
The author reviewed his computer database of gastric specimens detailing 10 000 consecutive gastric specimens taken over the last 12 years 2002-2013 at his pathology laboratory in a relatively large general hospital in Japan. Histological sections were examined when appropriate. Clinical records were also reviewed in the computer system. In appropriate cases, an immunohistochemical study was performed with the use of Dako Envision methods (Dako, Corp, Glustrup, Denmark), as previously described [2][3][4]. The antibodies employed were as follows: anti-cytokeratin (AE1/3 . In some cases, Giemsa staining was performed to identify Helicobactor pylori bacteria. A genetic analysis for the KIT (exons 9, 11, 13, and 17) and PDGFRA genes (exons 12 and 18) was performed in six cases of GIST. The exons of both genes were selected because they are frequent mutation sites in GIST [5][6][7][8][9][10]. DNA was extracted from the paraffin sections of the GIST and analysed by the PCR-direct sequencing method, as previously described [4,[11][12][13][14][15][16].
In the 1342 cases of gastric carcinoma, the histological type according to World Health Authority (WHO) classification was as follows [17]: tubular adenocarcinoma in 755 cases ( Figure 1A), papillary adenocarcinoma in 176, mucinous adenocarcinoma in 147, signet ring cell carcinoma in 145 ( Figure 1B), poorly differentiated adenocarcinoma in 114, adenosquamous carcinoma in 4, and metastatic small cell carcinoma from the lung in 1. In surgically resected cases, the number of early gastric carcinomas was 258 cases, plus 521 cases of advanced carcinoma. The gross classification of the early carcinoma according to the Japanese Society of Gastric Cancer was Type I 35 cases, Type IIa in 16 cases, Type IIb in 7 cases, Type IIc in 101 cases ( Figure 1C), Type IIc þ III in 86 cases, and Type III in 13 cases. The gross classification of advanced gastric carcinoma according to the Japanese Society of Gastric Cancer was as follows: Borrmann I in 91 cases, Borrmann II in 193, Borrmann III in 216 ( Figure 1D), and Borrmann IV in 21. Twenty-two (1.6%) cases of gastric carcinoma occurred in foveolar hyperplastic polyps ( Figure 1E). These carcinomas were well differentiated tubular adenocarcinomas without invasion. H. pylori was present in 85% of gastric carcinomas. Immunohistochemically, the gastric carcinoma cells were almost always positive for p53 protein ( Figure 1F) and showed high Ki-67 labeling.
In GIST (n ¼ 34), tumors were submucosal (Figure 2A) in 28 cases and subserosal in 6. There were 2 cases of epithelioid type and 32 cases of spindle cell type ( Figure 2B). The size of GIST ranged from 1-15 cm, with a mean of 5.6 cm. KIT (CD117) was positive in all cases ( Figure 2C), CD34 in 31, desmin 2, and S100 4. A genetic analysis was performed in six cases of GIST and showed a total of 6 mutations of exons 8, 11 and 13 of the KIT gene and exon 18 of the PDGFRA gene.
In MALT lymphoma (n ¼ 25), the macroscopic features are indistinguishable from those of early gastric carcinomas ( Figure 3A). Histologically, diffuse proliferation of centrocytelike cells (CCL) (Figure 3B), lymph follicle formation, plasma cell infiltration and lymphoepithelial lesions (LEL) ( Figure 3C) were seen in all the cases. H. pylori infection was noted in 92%. Immunophenotypes showed positive reactions for CD10, CD20 and CD79a, all of which are B-cell markers. Light chain restriction was present in 18 of the 25 cases.
In non-Hodgkin's lymphoma (n ¼ 19), 17 cases were of diffuse large B-cell lymphoma, positive for CD10, CD20 and CD79a ( Figures 4A and 4B), one was peripheral T-cell lymphoma, positive for CD3 and CD45RO, and one was NK-cell lymphoma, positive for CD56 and CD57.

Discussion
In Japan, the most common malignancy is gastric carcinoma, frequently seen in the present study. In Japan, many persons undergo gastric endoscopy, so that the gastric carcinoma is detected in an early stage. The present study also identified a significant number of early gastric carcinomas. A possible association between gastric cancer and H. pylori has recently been proposed. In the present study, the frequency of H. pylori was high and it is of interest that 22 early gastric carcinomas were found within gastric foveolar hyperplastic polyps, suggesting that foveolar hyperplastic polyps may be a pre-malignant lesion [18][19][20][21].
According to the consensus report on GIST by Fletcher et al. the malignant potential of GIST depends on tumor size and mitotic counts [22].
In the present series, there were 25 cases of MALT lymphoma, which is prevalent in the stomach [23]. This relatively new entity was in the past called reactive lymphoid hyperplasia [23][24][25][26][27][28]; the condition is often associated with H. pylori infection, as was the case in the present study.  Eradication of these bacteria often leads to cure of the MALT lymphoma [23][24][25][26][27][28].
Most gastric lymphomas are of B-cell type [28][29][30][31]. The peripheral T-cell lymphoma and NK cell lymphoma are very rare in the stomach. In our study, there were 19 cases of non-Hodgkin's lymphoma; 17 cases were of diffuse large B-cell lymphoma, 1 was peripheral T-cell lymphoma positive, and 1 was NK cell lymphoma.
In summary, this study reported the histopathology of various malignant lesions of the stomach. This report also provided the frequence of the gastric malignant lesions in a Japanese hospital.