Studies on p53, BAX and Bcl-2 protein expression and microsatellite instability in stage III (UICC) colon cancer treated by adjuvant chemotherapy: major prognostic impact of proapoptotic BAX.

We evaluated the expression patterns of proapoptotic BAX, antiapoptotic Bcl-2 and p53, the proposed upstream effector of these molecules, as potential prognostic markers in UICC stage III colon cancer by immunohistochemical staining. To identify high-frequency microsatellite instability (MSI+) individuals, we performed single-strand conformation polymorphism-based analysis for BAT26. A total of 188 patients who had received 5-fluorouracil (5-FU)-based adjuvant chemotherapy (5-FU/folinic acid or 5-FU/levamisole) were enrolled. Median follow-up was 84.5 months. We found that BAX, Bcl-2 and p53 protein expressions were high or positive in 59, 70 and 50% of 188 cases, respectively. MSI+ tumours were detected in 9% of 174 evaluable patients. BAX or Bcl-2 was correlated with a higher degree of differentiation or left-sided tumours (P=0.01 or P=0.03, respectively); MSI was correlated with right-sided tumours (P<0.0001). In contrast to p53, Bcl-2, or MSI, low BAX, advanced pN category, low grade of differentiation and treatment with 5-FU/levamisole were univariately associated with poorer disease-free survival (DFS) (P=0.0005, P=0.001, P=0.005 and P=0.01, respectively) and poorer overall survival (OS) (P=0.002, P=0.0001, P=0.003 and P=0.02, respectively). Besides pN category and treatment arm, BAX was an independent variable related to both OS and DFS (P=0.003 and P=0.001, respectively). In both univariate and multivariate analysis, the p53-/BAX high in comparison with the p53+/BAX high subset conferred a significantly improved DFS (P=0.03 and P=0.03, respectively) as well as a marginally improved OS (P=0.07 and P=0.08, respectively). BAX protein expression may be of central significance for clinical outcome to 5-FU-based adjuvant chemotherapy in stage III colon cancer, and bivariate analysis of p53/BAX possibly may provide further prognostic evidence.

Pyloric gland adenoma-- how to diagnose?

The term "pyloric gland adenoma" reflects its etiogenesis from deep mucoid glands in the stomach. The diagnosis can be confirmed by immunohistochemistry. Typically, pyloric gland adenomas are strongly positive for Mucin 6 (deep mucoid gastric glands). These lesions express Mucin 6 over the whole lesion up to the surface often only with a small layer of columnar epithelium expressing Apomucin 5AC. The amount of mucin 5AC which is expressed on normal within the apical foveolar epithelium might vary from case to case. Combination or transdifferentiation with ordinary tubular (intestinal differentiation) adenoma can be observed. The gastric corpus mucosa of elderly female patients with autoimmune gastritis is highly affected. The frequency of pyloric gland adenoma is given in the literature being 2.7% of all gastric polyps. Therefore pyloric gland adenomas are not that rare that one might assume. Only a few publications are available which makes one think that these lesions are frequently misinterpreted. Pyloric gland adenomas can arise in gastric heterotopia and gastric metaplasia in the whole gastrointestinal tract. The clinical significance is given by a 30% rate of malignant transformation. These cases represent for the most well differentiated early adenocarcinomas which are known to have an excellent prognosis after complete polypectomy and limitation to the mucosal layer.

Adenoma with gastric differentiation (so-called pyloric gland adenoma) in a heterotopic gastric corpus mucosa in the rectum.

In a 46-year-old man, a pedunculated rectal polyp measuring 3.0x3.0x2.0 cm was diagnosed histologically as a pyloric gland-type adenoma arising in heterotopic gastric corpus mucosa. The luminal site was covered by glands of the gastric foveolar type, displaying focal marked proliferation interpreted as low-grade intraepithelial neoplasia. A bidirectional gastric differentiation was found: most lower glandular structures showed positivity for the deep gastric mucin core protein Muc 6 and superficial positivity for gastric foveolar epithelium mucin core protein Muc 5AC. Pyloric gland adenoma has so far been described in one larger series only and a few case reports of the stomach, gallbladder, pancreatic duct and within heterotopic gastric corpus mucosa of the duodenal bulb. The present case report is the first case of a pyloric gland-type adenoma within a gastric corpus heterotopia of the rectal mucosa.

[Pancreatic tail tumor as an unusual first manifestation of Wegener's disease]. / Pankreasschwanztumor als ungewöhnliche Erstmanifestation eines M. Wegener.

A fifty-year-old, previously healthy woman presented with abdominal pain and weight loss. Diagnostic work-up revealed a mass in the tail of the pancreas with the appearance of a pancreatic carcinoma. Partial pancreatectomy was performed. Postoperatively, the patient's kidney function deteriorated. Pathohistological examination of the resected tissue showed a granulomatous vasculitis but no maligant tumor. Renal biopsy revealed a rapid progressive glomerulonephritis. Positive C-ANCA screening confirmed the diagnosis of Wegener's disease and an immunosuppressive therapy was established. This case demonstrates the difficult management of a potentially benign pancreatic mass, as reliable discrimination from pancreatic adenocarcinoma is not always possible.

Molecular lesions in colorectal cancer: impact on prognosis? Original data and review of the literature.

BACKGROUND: In the Dukes' B and C stages of colorectal carcinoma there are considerable variations in the observed courses of the disease. Since post-operative chemotherapy in patients with Dukes' C (node-positive) colon carcinoma has been demonstrated to be effective in improving overall-survival, a more exact prognosis assessment gains additional significance and therapeutic relevance. DISCUSSION: One also hopes to derive improved prognostic factors from the clarification of the molecular pathogenesis. Because of its frequency and the accessibility and recognizability of its developmental stages colorectal carcinoma is among the best investigated of all solid tumors. Despite a multitude of suggested molecular candidate markers none of these changes has yet been able enter the everyday life of the clinic. However, it is to be expected that some of the molecular alterations presently discussed will gain importance before long in the clinical treatment of patients with colorectal carcinoma. CONCLUSION: Considering also our own findings, this review presents the latest developments in the scientific discussion of the tumor suppressor/oncogenes p53, k-ras, and DCC, biochemical determinants of the 5-fluorouracil metabolism, and defects of the DNA repair system.

Histopathological diagnosis of Barrett's mucosa and associated neoplasias: results of a consensus conference of the Working Group for Gastroenterological Pathology of the German Society for Pathology on 22 September 2001 in Erlangen.

There are a number of difficulties regarding the diagnosis of Barrett's mucosa and the varying grades of neoplasia that may be associated with it. It was, therefore, the aim of a consensus conference of the Working Group for Gastroenterological Pathology within the German Society of Pathology to achieve standardisation regarding the following issues: definition and diagnostic criteria for Barrett's mucosa and its discrimination from intestinal metaplasia of the cardia, diagnostic criteria for intraepithelial neoplasia, number of biopsies necessary to establish the diagnosis, significance of additional immunohistochemical and/or molecular methods as well as importance of a second opinion in the diagnosis of intraepithelial neoplasia.

Pyloric gland adenoma: a clinico-pathological analysis of 90 cases.

BACKGROUND: Pyloric gland adenoma is a rarely described neoplasia of the gastric mucosa. Recent publications have shown that similar lesions are also found in the gallbladder, the main pancreatic duct, the duodenum and the cervix of the uterus. Apart from case reports, few clinical data are available on these patients. We therefore conducted a search of the archived material collected between 1990 and 2000 for more clinical data on patients with this rare lesion. PATIENTS AND METHODS: Between 1990 and 2000, 90 patients were diagnosed as having a pyloric gland adenoma in the stomach (77 patients), duodenal bulb (7 patients), duodenum (1 patient), bile duct (3 patients) or gallbladder (2 patients). RESULTS: Pyloric gland adenomas account for 2.7% of all gastric polyps and occur predominantly in old age (73+/-12.8 years), more frequently in women (75%) than in men. The predilection site in the stomach is the corpus mucosa (64%) and they are often found in patients suffering from autoimmune gastritis (36%). At the time of diagnosis, pyloric gland adenomas measure 16.1+/-9.1 mm in size. In 30% of gastric pyloric adenomas, transition to well-differentiated adenocarcinoma has been noted. DISCUSSION: In our material, pyloric gland adenoma is the third most common neoplastic polypoid lesion in the stomach. Since a search through the literature revealed only a few case reports on this lesion, it is possible that for some reason this lesion might be diagnosed more often than reported. CONCLUSION: Our study revealed that 30% of the gastric pyloric gland adenomas showed continuous transition to well-differentiated adenocarcinoma at the time of the initial diagnosis. This underscores the malignant potential of the lesion, and the need for polypectomy.

[Histopathological diagnosis of Barrett's mucosa and associated neoplasias. Results of a consensus conference of the Working Group for "Gastroenterological Pathology of the German Society for Pathology" on 22 September 2001]. / Histopathologische Diagnostik der Barrett-Schleimhaut und ihrer Neoplasien. Ergebnisse einer Konsensus-Konferenz der Arbeitsgemeinschaft "Gastroenterologische Pathologie der Deutschen Gesellschaft für Pathologie" am 22. September 2001 in Erlangen.

There are a number of difficulties regarding the diagnosis of Barrett's mucosa and the varying grades of neoplasia that may be associated with it. It was therefore the aim of a consensus conference of the "Working Group for Gastroenterological Pathology within the German Society of Pathology" to achieve standardization regarding the following issues: definition and diagnostic criteria for Barrett's mucosa and its discrimination from intestinal metaplasia of the cardia, diagnostic criteria for intraepithelial neoplasia, number of biopsies necessary to establish the diagnosis, significance of additional immunohistochemical and/or molecular biological methods as well as importance of a second opinion in the diagnosis of intraepithelial neoplasia.

Flow cytometric and histologic evaluation in a large cohort of patients with ulcerative colitis: correlation with clinical characteristics and impact on surveillance.

PURPOSE: To examine the prevalence of DNA aneuploidy as a function of the extent of ulcerative colitis and to study the correlation of aneuploidy with clinical characteristics. Furthermore, the occurrence of aneuploidy and dysplasia during colonoscopic surveillance was studied in a subset of these patients. METHODS: By analyzing 5404 biopsy samples of 368 patients with ulcerative colitis, we have evaluated the importance of DNA ploidy measured by flow cytometry. We have also investigated the influence of extent (219 patients with extensive or total colitis vs. 149 patients with localized colitis) and duration of colitis on the development of dysplasia (patients with biopsy specimens that showed inflammation alone were compared with those with biopsy specimens that were equivocal or positive for dysplasia) and aneuploidy. Included was a subgroup of patients with ulcerative colitis and primary sclerosing cholangitis (n = 16). RESULTS: Aneuploidy was found in 8.7 percent (32/368) of all patients. The prevalence of aneuploidy increased by the extent of ulcerative colitis (2 percent localized, 6.8 percent extensive colitis, 14.9 percent total colitis). The frequency of aneuploidy was higher in patients with disease duration longer than 10 years (P = 0.007). Patients with ulcerative colitis and primary sclerosing cholangitis were more likely to develop aneuploidy (9/16, 56.3 percent vs. 14/120, 11.7 percent; P < 0.001) and dysplasia (4/16, 25 percent vs. 10/120, 8.3 percent; P = 0.06) than patients without primary sclerosing cholangitis. CONCLUSION: Because DNA aneuploidy represents an early alteration during neoplastic transformation in ulcerative colitis, flow cytometry is a valuable tool in the surveillance of those patients. Primary sclerosing cholangitis represents an additional risk factor for the development of DNA aneuploidy and dysplasia.

Comparative genomic hybridization analysis of chromosomal alterations in patients with long-standing ulcerative colitis.

Patients with ulcerative colitis (UC) are prone to develop colorectal cancer which is related to the duration and extent of the disease. One of the earliest events in tumor progression is the development of aneuploidy. Aneuploidy is correlated with the grade of dysplasia which serves as a common but not always reproducible marker for the prediction of UC associated formation of cancer. We analyzed 48 biopsy samples from 5 patients with long-standing ulcerative colitis by comparative genomic hybridization (CGH). The majority of these samples represented premalignant stages which are not well characterized at the molecular level as yet. We compared biopsy samples from different colon locations in regard to chromosomal alterations, dysplasia status and DNA index. Besides chromosomal changes occurring only in certain patients in restricted areas of the colon we also detected amplifications and deletions which were common in all persons throughout the colon. The stage of dysplasia seems to have no influence on the number and appearance of chromosomal changes. Amplifications in 2, 3, 6, 9, 11, 12 and 15 were found in almost all cases. In dysplastic samples chromosomal regions 3, 6 and 11 revealed gains of DNA. Deletions were detected within 8q, 15, 18q, 20p and 22q. The affected chromosomal regions may contain yet unknown oncogenes or tumor suppressor genes participating in UC associated carcinogenesis. The conspicuous regions found in the CGH experiments allow the selective and detailed characterization at a molecular level.

[Study Group of Gastroenterological Pathology of the German Society of Pathology. Recommendations for celiac disease/sprue diagnosis]. / Arbeitsgemeinschaft für gastroenterologische Pathologie der Deutschen Gesellschaft für Pathologie. Empfehlungen zur Zöliakie-/Spruediagnostik.

The diagnosis of celiac disease (CD) is based upon histological findings in duodenal or jejunal biopsies. In the past few years it has turned out that the development of CD lesion in the small bowel is a dynamic process which may present in various histological forms. At one end of the spectrum is a mucosa with normal architecture and an increase in intraepithelial lymphocytes (IEL), at the other end is the classical flat mucosa. Histological features supporting the diagnosis of CD are architectural changes of the villi and/or crypts, an increase in lamina propria cell density and an increase in IEL counts. For diagnostic purposes and for monitoring of CD patients an exact histological classification of the histological findings has to be given. This has become possible by using a modified Marsh classification. In the present paper the histological presentation of CD is presented as well as the modified Marsh classification and the most important differential diagnoses.

[Chemical-reactive gastritis]. / Chemisch-reaktive Gastritis.

Chemical or reactive gastritis is commonly induced by endogenous substances such as bile and pancreas secretions, but can it also be caused by exogenous noxious substances, including acetylsalicylic acid, nonsteroidal anti-inflammatory drugs, chemotherapeutics, and alcohol. The histopathological patterns are similar, involving epithelial damage extending up to erosions with consecutive regenerative hyperplasia and damage to capillaries, with edema, hemorrhage, and proliferation of smooth muscles. As cellular infiltrates are minimal or lacking, some authors have proposed the term "gastropathy" instead of the term chemical or reactive gastritis as proposed by the updated Sydney classification. This contribution describes the different patterns and grades and discusses their pathogenesis. Mixed forms of chemical/reactive gastritis and other forms of gastritis are also described, for example, that from Helicobacter.

[Diagnosis of celiac disease and sprue. Recommendations of the German Society for Pathology Task Force on Gastroenterologic Pathology]. / Empfehlungen zur Zöliakie-/Spruediagnostik. Arbeitsgemeinschaft für gastroenterologische Pathologie der Deutschen Gesellschaft für Pathologie.

The diagnosis of celiac disease (CD) is based upon histological findings in duodenal or jejunal biopsy specimens. In recent years it has been seen that the development of CD lesion in the small bowel is a dynamic process which may present in various histological forms. At one end of the spectrum is a mucosa with normal architecture and an increase in intraepithelial lymphocytes; at the other end is the classical flat mucosa. Histological features supporting the diagnosis of CD are architectural changes of the villi and/or crypts, an increase in lamina propria cell density, and an increase in intraepithelial lymphocytes counts. Exact histological classification of the histological findings is required for diagnostic purposes and for monitoring of CD patients. This has become possible by using a modified Marsh classification. We present both the histological presentation of CD and the modified Marsh classification, and the most important differential diagnoses.

The prognostic value of S-phase fraction in preoperative radiotherapy of rectal cancer.

The aim of this study was to analyze the flow cytometric S-phase fraction (SPF) in rectal tumors before and after preoperative radiotherapy (15x2 Gy) and to compare the findings to the clinical outcome. Archival specimens from 84 cases, treated from 1980 to 1988 with S-phase data and complete follow-up were reviewed. There was no significant correlation between SPF and clinicopathological factors. The median SPF for the 26 diploid tumors before irradiation was 6.6%+/-3.1, compared to a significantly higher median for the 58 preirradiated aneuploid tumors (20.3%+/-6.1; p<0.0001). With a median follow-up of 6 years, there was a significant difference in the number of recurrences for aneuploid tumors with a pretreatment SPF < and >20.3 (51.7% vs. 20.7%; p=0.029), which also led to a significant difference in recurrence-free survival (p=0.05). For diploid tumors, a reduction in the percentage of cells in S-phase after radiation resulted in a borderline significant lower number of recurrences (p=0.06). It is concluded that pretreatment S-phase measurements may be of predictive value especially for aneuploid tumors. An alteration in SPF after radiotherapy may also be helpful in predicting outcome and planning therapy.

Comparison of flow cytometry and histology with mutational screening for p53 and Ki-ras mutations in surveillance of patients with long-standing ulcerative colitis.

BACKGROUND: We evaluate the usefulness of screening for p53 and Ki-ras mutations in comparison with histological and flow cytometric findings. METHODS: We analyzed 1486 biopsy samples from 769 locations of 83 patients with long-standing ulcerative colitis enrolled in a surveillance program by means of histology, flow cytometry and SSCP analysis. As a control we used 66 biopsy samples of 16 patients with irritable bowel disease. RESULTS: With respect to all biopsy samples analyzed, DNA aneuploidy was found in 32.5% (27/83) of patients, dysplasia in 22.9% (15/83), p53 in 21.7% (18/83) and Ki-ras mutations in 18.1% (15/83) of patients. None of these markers was found in our control group. In 7 out of 10 patients who displayed dysplastic findings during endoscopic surveillance p53 and / or Ki-ras mutations were present in at least one colonoscopy. Statistically significant associations were observed between dysplasia and DNA aneuploidy (P < 0.001), between dysplasia and p53 mutations (P = 0.05) and between dysplasia and p53 and/or Ki-ras mutations (P = 0.002). No significant associations were found between dysplasia and Ki-ras mutations alone. The results for the SSCP analysis showed a much broader variation than those for the flow cytometric analysis. CONCLUSIONS: These results show that screening for p53 and Ki-ras mutations can be a useful adjunct in surveillance of patients with long-standing ulcerative colitis.

Alteration of DNA ploidy status and cell proliferation induced by preoperative radiotherapy is a prognostic factor in rectal cancer.

To identify predictors of prognosis after preoperative radiotherapy, DNA ploidy and cell proliferation were investigated in 116 patients with rectal cancer. For flow cytometry, a nuclear suspension was prepared by pepsin digestion of paraffin samples of biopsies taken before preoperative radiotherapy (15 x 2 Gy) and also of the resected rectal tumors after radiotherapy. The median follow-up period was 6 years. The proportion of tumor necrosis was evaluated in histological sections before and after irradiation. There was a significant decrease (74 to 48%) in aneuploid tumors after radiation. Of 86 patients with aneuploid biopsies, 28 revealed no reduction in the proportion of aneuploid tumor cells [group AN(=/increase)], and 58 showed a reduction (mean 48.9%) or complete elimination of aneuploid tumor cells [group AN(decrease/psi)]. The incidence of local or distal failure was significantly reduced in the group AN(decrease/psi) (7.8%/20%), compared with the group AN (=/increase) (27%/54%) and the group of constant diploid tumors (n = 22; 13.6%/31.8 %; P = 0.034). There was a trend of decreased recurrence rate in diploid tumors with a reduced fraction of cells in S-phase after radiotherapy. Survival was significantly increased in group AN(decrease/psi) (P < 0.0001). In a multivariate regression analysis, variables of independent prognostic significance were increased proportion of necrosis after irradiation and DNA ploidy group and the postoperative tumor stage. These results suggest that alterations in tumor DNA ploidy and cell proliferation induced by preoperative radiotherapy might help to identify patients likely to benefit from preoperative radiation in rectal cancer.

The Vienna classification of gastrointestinal epithelial neoplasia.

BACKGROUND: Use of the conventional Western and Japanese classification systems of gastrointestinal epithelial neoplasia results in large differences among pathologists in the diagnosis of oesophageal, gastric, and colorectal neoplastic lesions. AIM: To develop common worldwide terminology for gastrointestinal epithelial neoplasia. METHODS: Thirty one pathologists from 12 countries reviewed 35 gastric, 20 colorectal, and 21 oesophageal biopsy and resection specimens. The extent of diagnostic agreement between those with Western and Japanese viewpoints was assessed by kappa statistics. The pathologists met in Vienna to discuss the results and to develop a new consensus terminology. RESULTS: The large differences between the conventional Western and Japanese diagnoses were confirmed (percentage of specimens for which there was agreement and kappa values: 37% and 0.16 for gastric; 45% and 0.27 for colorectal; and 14% and 0.01 for oesophageal lesions). There was much better agreement among pathologists (71% and 0.55 for gastric; 65% and 0.47 for colorectal; and 62% and 0.31 for oesophageal lesions) when the original assessments of the specimens were regrouped into the categories of the proposed Vienna classification of gastrointestinal epithelial neoplasia: (1) negative for neoplasia/dysplasia, (2) indefinite for neoplasia/dysplasia, (3) non-invasive low grade neoplasia (low grade adenoma/dysplasia), (4) non-invasive high grade neoplasia (high grade adenoma/dysplasia, non-invasive carcinoma and suspicion of invasive carcinoma), and (5) invasive neoplasia (intramucosal carcinoma, submucosal carcinoma or beyond). CONCLUSION: The differences between Western and Japanese pathologists in the diagnostic classification of gastrointestinal epithelial neoplastic lesions can be resolved largely by adopting the proposed terminology, which is based on cytological and architectural severity and invasion status.

International comparability of the pathological diagnosis for early cancer of the digestive tract: Munich meeting.

Large differences have been found between Western and Japanese pathologists' diagnosis of adenoma/dysplasia versus early carcinoma for gastric, esophageal. and colorectal epithelial neoplastic lesions. In this study we examined whether differences in experience in gastrointestinal pathology can to some extent explain these differences in diagnostic practice. Three Japanese, one British, and two German pathologists with much experience and one North American pathologist with less experience in routine diagnostic work reviewed 52 microscopic slides: 16 gastric, 24 esophageal, and 12 colorectal biopsy and resection specimens obtained from patients with lesions ranging from early carcinoma to adenoma, dysplasia, and regenerative epithelium. The extent of agreement between the diagnoses of the four individual Western pathologists and the most common Japanese diagnoses was assessed by kappa statistics. For the 16 gastric lesions, a diagnosis of suspected or definite carcinoma was made by the Japanese pathologists in 69%-75% of the slides, by three experienced Western pathologists in 56%-63% (high kappa values: 0.61, 0.64, 0.65), and by the less experienced Western pathologist in only 31% of the slides (low kappa value: 0.10). For the 24 specimens of esophageal squamous lesions, carcinoma in situ and suspected or definite carcinoma were diagnosed by the Japanese in 96%-100% and by the Western pathologists in 63%-88% of the slides (low kappa values: 0.17, 0.25, 0.25, 0.27). For the 12 colorectal lesions, the Japanese diagnosed suspected or definite carcinoma in 58%-83%, whereas all Western pathologists followed the World Health Organization definition of colorectal carcinoma and diagnosed suspected or definite carcinoma in only 0-42% of the slides (kappa values: 0.04, 0.10,0.12, 0.49). In conclusion, there were few differences in diagnoses between experienced Western and Japanese pathologists for gastric lesions but considerable differences for esophageal and colorectal lesions. The differences in the diagnosis of adenoma/dysplasia versus early carcinoma between Western and Japanese pathologists found in previous studies may in large part be attributable to differences in experience with regard to gastric neoplasia and to differences in interpretation and nomenclature with regard to esophageal and colorectal neoplasia.

Telomerase activity in long-standing ulcerative colitis.

Telomerase activity is frequently associated with neoplasia. It is a ribonucleoprotein capable of replacing telomeric DNA sequences that are lost at each cell division. Neoplastic progression in chronic ulcerative colitis is characterized by the development of epithelial dysplasia which is accompanied by genetic alterations. Therefore we tested telomerase activity in 128 biopsy samples of four colectomy specimens with long-standing ulcerative pancolitis by using the Telomerase PCR ELISA System. In three patients with multiple dysplastic or carcinomatous lesions, telomerase activity was detected in 22 samples with a regional association to dysplastic or carcinomatous areas. 15 of the samples with telomerase activity (68%) were found in dysplastic/carcinomatous samples or in the direct vicinity of dysplastic areas, 4 (18%), 2 positions (about 4 cm) and the remaining three (14%) not more than 3 positions away from such areas. In the fourth patient, resected because of clinical deterioration despite medical treatment and who had no dysplastic lesions, no telomerase activity was detected. These results show that telomerase activity might be used as a complementary marker to histology for the identification of patients with ulcerative colitis who are at an increased risk for neoplastic progression.

[Forms and nomenclature of gastrointestinal epithelial expansion: what is invasion?]. / Formen und Nomenklatur der gastrointestinalen Epithelexpansion: Was ist Invasion?

In the gastrointestinal (GI) glandular mucosa, the term invasion is ill defined until today. In order to standardize the nomenclature of the expansion of benign and early malignant tumors of the glandular epithelium, we tried to establish a new descriptive terminology: In adenomas, the first glands with neoplastic epithelium may be divided by gland fission before there is primary superficial lateral expansion, followed by luminal expansion in form of budding, glandular fission and minimal branching, and a secondary downward vertical intra- and intertubular expansion into the mucosa. The different growth types of GI adenomas differ in the proportion of these components which will be considered below. In contrast, mucosal carcinomas usually do not show superficial lateral expansion, but they are usually characterized by a primary midmucosal disorderly lateral intertubular expansion with irregular branching and fusion of neoplastic glands, with undermining of the surface epithelium, and with compression and destruction of neighbouring glands by lateral and downward expansion of the neoplastic epithelium, finally with secondary erosions. This pattern of lateral intertubular expansion is indicative for carcinomatous invasion in GI mucosal carcinomas. The permeation of basal membranes usually does not occur in well differentiated carcinomas, which form new basal membranes. With increasing loss of differentiation, there is tumor cell dissociation with permeation or no production of basal membranes up to the pure diffuse type carcinoma; this process of invasion across basal membranes is merely one, but not the only sign of invasion, in our view. A fibrous stromal reaction usually does not occur in the mucosa, but it is most intense in the submucosa and subserosa, and much less pronounced in the muscularis propria. This fibrous stromal reaction is also indicative for invasion. However, Japanese pathologists do not diagnose malignancy only from architectural signs of invasion but mainly from cytological criteria, which also have to be considered aside from structural criteria given above. In comparison, epithelial growth in metaplastic processes is restricted to intratubular expansion or glandular fission without superficial lateral expansion. Pseudoinvasions of cohesive and diffuse types have to be considered for differential diagnosis.