Original contributionLower- and higher-grade subtypes of diffuse gastric cancer☆
Introduction
Gastric diffuse cancer is characterized by poorly cohesive, diffusely infiltrating cells with little or no gland formation [1], [2]. Five morphologic variants of neoplastic cells are mentioned in the World Health Organization 2000 classification book, that is, signet ring, histiocytoid, eosinophilic, small mucin poor, and anaplastic cells, without documented differences concerning prognosis or natural history of the disease. With the exception of early-stage tumors, normally presenting as intramucosal or type B penetrating submucosal cancer [3], diffuse gastric cancers are usually reported to have rather poor prognosis, irrespective of their histologic features [2], [4], [5], [6], [7], despite past suggestions by Kubo [8] of less malignant behavior of a “desmoplastic” variant with prominent stroma compared with signet ring or anaplastic subtypes.
During a retrospective investigation of several hundred gastric cancers with available prolonged follow-up (median of more than 10 years) [9], we observed several instances of diffuse cancers with prominent desmoplasia surrounding individual tumor cells, which showed a relatively more favorable outcome, although other cancers with abundant desmoplasia showed worse behavior. In addition, a trend for diffuse cancers with anaplastic cells to show worse prognosis was noticed in the same as well as in a previous series [9], [10]. Therefore, we undertook a systematic reinvestigation of histopathologic patterns of diffuse gastric cancer and its variants, searching for any distinctive feature that might help to characterize subgroups of different clinicopathologic behavior and prognosis. In addition to purely morphologic features of tumor cells and stroma, histochemical reactivity for differentiation (mostly secretory) markers potentially informative for tumor cell lineage [11], [12], [13], [14] was also investigated.
Section snippets
Materials and methods
Gastric cancers showing diffusely infiltrating poorly cohesive cells, dispersed in the stroma as single elements or in small aggregates with little or no gland formation, were retrieved from the files of the Departments of Pathology of the Universities of Insubria, Pavia and Genoa, among cases which had undergone surgery between 1980 and 1987 at Varese General Hospital, between 1984 and 2000 at San Matteo Policlinico in Pavia or during 1998 to 1999 at San Martino General Hospital in Genoa,
Results
Among the 119 diffuse cancers investigated, 53 tumors with prominent desmoplasia were separated from 24 cases with a predominance of mucin-storing cells (signet ring cell cancers), 14 cancers mainly or essentially formed by anaplastic cells, and 24 tumors not otherwise specified lacking a clearly predominant pattern. It should be noted that desmoplasia was a relevant feature only in the invasive (submucosa or beyond) part of the cancers investigated, whereas it was lacking in their intramucosal
Discussion
In this article, 2 histologically distinct subtypes of diffuse gastric cancer have been identified and separated from the bulk of diffuse tumors, that is, a low-grade desmoplastic and a high-grade anaplastic cancer. The lower-grade subtype was characterized by a prominent desmoplasia surrounding and apparently entrapping tumor cells, low tumor cellularity, no or scarce mucin production, moderate nuclear atypia and proliferative rates, no angioinvasion, and no or only sporadic lymphoinvasion and
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2011, Human PathologyCitation Excerpt :On the other hand, a poor prognosis had been predicted by other genomic lesions, as, for instance, specific p53 mutations [6]. However, scarce information is available on genome-wide molecular analysis of prognostically informative histologic subtypes, because most of the studies published so far are based on broad tumor categories like intestinal and diffuse histotypes [7-12] or histologically more descriptive types [13,14], which are themselves of limited prognostic value [15,16], rather than on histologic types specifically designed to predict patient outcome [1-6]. In this study, a sample of 81 invasive (from T1b, deep submucosa, to T4 and stages I to IV) gastric cancers, representing the main histologic types and subtypes, were selected from a larger series of cases that had already undergone histologic, histochemical, and molecular investigation (4-6).
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The investigations were supported in part by grants from the Italian Ministry of Health (RF-PSM-2006-401346), the University of Pavia (FAR 2006), and the University of Insubria.