5. Comments on the Variability of the Diagnoses

At first glance, the variability in the histological differential diagnosis of early epithelial neoplasia of the stomach, first reported by Schlemper et al. [1] and subsequently confirmed in further reports [2–4], is alarming. This variability then gave rise to critical comments [5]. One gastroenterologist was even moved to give his comments the title “Japanese Fairy Tales,” [6] and concluded “The high prevalence of early gastric carcinoma in Japan and the successes in combating carcinoma of the stomach are possibly nothing but an artefact.” This commentator, however, overlooked the fact that one of the Western pathologists established exactly the same diagnoses, as did the four Japanese pathologists. He also failed to note that, in contrast to this group of four Japanese and one Western pathologist, the diagnoses made by the three other Western pathologists in forceps biopsy material differed considerably from their own diagnoses in the mucosectomy specimens from the same patients. Similar variable results in identical specimens were also revealed by the slide seminar that led to the compromise Vienna classification of gastrointestinal epithelial neoplasia [7], so that we might be justified in claiming that, in this area the term “Western deficiency” might be a more accurate comment than “Japanese fairy tales.” [8]

The uncertainty of many Western pathologists in differentiating between dysplasia and well-differentiated carcinoma of the stomach was already known from a number of follow-up studies of high-grade dysplasia of gastric mucosa. In 80% of these cases, a carcinoma was diagnosed within the very short average follow-up time of 6 months [9–16]. This uncertainty is readily understandable since, in comparison, the Japanese pathologists have much greater experience as a result of the much more common endoscopy/biopsy diagnosis of early carcinoma, and the much more frequently practiced endoscopic mucosectomy [17]. Fewer examinations coupled with less training in this area is therefore the likely explanation for the diagnostic uncertainty of many Western pathologists [18].

However, at second glance, the diagnostic discrepancies are not particularly serious in terms of clinical consequences. Only very rarely did a Western pathologist underdiagnose a neoplasm as regenerative change. In almost all cases, neoplasia was correctly diagnosed in the biopsy specimen with the result that, on the basis of

the endoscopic findings, the diagnosis would almost always lead to the correct consequence of endoscopic, and not surgical, therapy.

As a subscriber to Stomach and Intestine and as a frequent guest in Japan, I learned a great deal from my Japanese colleagues, and early on abandoned the dogma—still upheld by many in the West—that stresses the need to detect isolated invasive tumor cells to establish the diagnosis of invasive carcinoma. I was particularly helped in this respect by the work of Takahashi and

Iwama [19–21]. In their three-dimensional reconstructions of the microstructures of well-differentiated tubular adenocarcinomas of the stomach, these authors demonstrated that the carcinomatous tubuli invasively penetrated the lamina propria of the mucosa and anastomosed with the neighboring tubuli to form a network of neoplastic tubuli. The discovery of such a network shows that invasive growth through the lamina propria is present. When these tubuli then infiltrate the muscularis propria and the upper part of the submucosa— without separated tumor cells and with intact basement membrane—Western pathologists also diagnose invasive carcinoma, as in the case of lymph node metastases in well-differentiated adenocarcinomas located elsewhere.

This concept of invasion was also convincingly represented by Borchard [22]: while superficial lateral expansion, luminal extension, and a vertical intratubular extension dominate in adenomas, well-differentiated tubular adenocarcinoma limited to the mucosa has a quite different growth pattern. This “growth pattern of invasion” is characterized by primarily lateral intertubular expansion which is located not in the surface but in the middle part of the mucosa. These abnormally branched carcinomatous glands, without tumor cell dissociation or penetration of atypical epithelial cells through the basement membrane, may lead to secondary changes such as compression and pressure atrophy of neighboring glands, and erosion.

The fact that five of the Western pathologists established their diagnoses in the same manner as their

Japanese colleagues shows that this “Japanese viewpoint” has increasingly gained ground outside of Japan too. May the cases discussed in this book help this concept to achieve further international acceptance.

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