Linitis is a histological form of cancer that primarily affects the stomach and was first described by Brinton in 1859 [1] and Borrmann in 1926 [2]. Linitis plastica lesions are adenocarcinomas whose cell populations are more than 50% “independent signet ring” cells. The lesions have a characteristic “frozen” aspect, infiltrating the bowel wall up to the lamina propria [3]. The prognosis is poor compared to other types of cancer; therefore, early diagnosis is critical [4, 5].

Gastroscopy is often used as an initial examination to establish a diagnosis, determine tumor extent, and provide histological proof of the disease. However, gastroscopy findings are often falsely negative, as only the mucosal wall is analyzed, and superficial biopsies are negative in this setting [6, 7].

Linitis can affect any part of the digestive tract and may be primary or secondary [8]. Although there are several published studies about gastric linitis and case reports of extra-gastric forms, we are aware of no epidemiological studies of this type of cancer within a particular population. In addition, the radiological findings of gastrointestinal linitis are poorly documented. “Linitis plastica” is a term that is typically used on the endoscopic and macroscopic plane; therefore, we aimed to correlate the histological definition of this condition (namely, “scirrhous carcinoma with more than 50% of signet ring cells”) into the realm of imaging. The aim of this study was to analyze the computed tomography (CT) features of gastrointestinal linitis plastica, determine the frequency of involvement of different sites, and assess its primary or secondary nature.

Materials and methods

Study population

This single-center, retrospective study analyzed all cases of gastrointestinal linitis observed over the 10-year period spanning from January 2003 to September 2014 at Nancy Regional University Hospital in France. The institutional review board approved the study and did not require additional informed consent for reviewing the patients’ medical records and images. A search of digital radiological reports using the terms “gastric linitis plastica” or “linitis plastica” identified 80 eligible patients. Following this, a search of digital pathological reports using the terms “linitis plastica” and “scirrhous carcinoma with more than 50% of signet ring cells” confirmed 65 of the cases.

Of the 65 cases, 45 patients with both firm pathological diagnosis and available pre-treatment imaging studies were enrolled (eight of the originally identified patients had only post-treatment imaging available, two of the originally identified patients underwent chemotherapy, and ten of the originally identified patients had no access to imaging) (Fig. 1). General data, such as patient's age and sex, mode of discovery, and history of malignancy, were also analyzed.

Fig. 1
figure 1

Flowchart of case selection

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Collection of imaging data

Imaging data were retrieved from our PACS (Picture Archiving and Communication System). All patients underwent thoraco-abdominopelvic or abdominopelvic CT using various devices (Scan Lightspeed, General Electric, 16- to 64-array). The CT protocol included the injection of an iodinated contrast agent and the collection of images during the arterial phase and the delayed portal post-equilibrium phase. The arterial phase images were acquired 35 s after the injection of 80–120 mL of non-ionic contrast material (XENETIC 350 or IMERON 350, depending on the body weight) at a rate of 3 mL/s, and the delayed phase images were acquired 2 min after injection. Portal phase images were acquired 65 s after injection, but we did not include this phase in our analysis. Reconstructed images of 3- or 5-mm slice thickness were used for assessment.

Reading of CT scans

Two radiologists independently read the CT images according to Appendix. This included one junior radiologist (CB, a 3rd year radiology resident) and one senior radiologist (VL, a radiologist with over 20 years of experience, including 15 years in abdominal imaging).

Qualitative data collection

The following radiological features were analyzed (Fig. 2) (Appendix):

Fig. 2
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Regular diffuse thickening of the gastric wall with early arterial enhancement of the mucosal-submucosal complex (A) and delayed enhancement of the entire wall (B) indicating diffuse gastric linitis

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  • Lesion characteristics, such as the presence of mass syndrome, gastrointestinal wall thickening (>5 mm for the stomach [9]; >3 mm for the small intestine, colon and anus [10]), and wall atrophy (<1 mm).

  • Wall thickening, which was categorized as either segmental (<0 cm in length) or diffuse (affecting the entire organ). Fold disappearance, involvement beyond the serous layer, and the presence of stenosis were also recorded.

  • Lesion enhancement kinetics, which were recorded as no enhancement, enhancement during the early arterial phase of the mucosal-submucosal complex (corresponding to the two innermost layers of the gastrointestinal wall), and/or enhancement during the delayed phase of the entire lesion (fibrous type).

  • Linitis was considered secondary if a patient had a history of cancer and primary in all other cases. When multiple synchronous lesions were detected, gastric site lesions were considered to be primary, and the others were considered to be metastatic.

Quantitative data collection

The following quantitative CT data were collected (Fig. 3):

Fig. 3
figure 3

Antropyloric linitis. CT images were analyzed for contrast enhancement. Density ROIs were determined on acquisitions without contrast (A), and the delayed phase (B), length (C), and thickness of the lesion (D) were calculated

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  • The two maximum cross-sectional diameters (in mm) when there was a mass.

  • The maximum thickness (in mm) in cases with wall thickening.

  • The maximum length (in mm) of segmental thickening.

Enhancement was quantified using density region of interest (ROIs) (in Hounsfield units (HU)) of 50 mm2 located in the region of wall thickening on acquisitions without contrast injection when they were available. The following assessments were made during the delayed portal post-equilibrium phase: density (HU) without contrast injection, density (HU) in the delayed portal post-equilibrium phase, and density variation (ΔHU) between the two acquisitions.

Results

Clinical data

The study population consisted of 23 men and 22 women (51.1%/48.9%), with an average age of 63.2 years (range 31–86). The presenting signs and symptoms were poor general health and/or ascites (n = 22), abdominal pain (n = 7), ulcer or dysphagia (n = 4), jaundice (n = 3), or an obstructive syndrome (n = 2). Seven patients presented with anuria, anemia, or hematemesis, while the diagnosis was incidental in four cases (Fig. 4).

Fig. 4
figure 4

Conditions underlying the discovery of linitis

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CT findings

Epidemiological data

A total of 60 lesions were detected in 45 patients (1.3 lesions/patient). These lesions were found in the stomach (n = 41, 68.3%), colon (n = 6, 10%), rectum (n = 7, 11.7%), sigmoid (n = 2, 3.3%), small intestine (n = 2, 3.3%), duodenum, and anus (one case each, 1.7%). No esophageal lesions were found. The majority (73.3%) of the lesions were primary, while 26.7% (n = 16) were secondary (from gastric linitis, n = 7; breast cancer, n = 5; bladder urothelioma, n = 2; non-Hodgkin’s lymphoma, n = 1; and hepatocellular carcinoma, n = 1). The secondary tumors were metachronous with the primary tumors in 43.7% of cases (n = 7).

Solitary lesions were found in 77.8% (n = 35/45) of the patients. The maximum number of lesion sites per patient was 3 (Fig. 5).

Fig. 5
figure 5

Double rectal and ileal localization of linitis. A contrast-enhanced CT scan showing regular diffuse thickening (arrow) of the rectum (A) and regular wall thickening (dotted arrow) of the last ileal loop (B, C) with a delayed enhancement of the lesions

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Imaging features

We observed wall thickening in 55 cases (91.7% of lesions), mass syndrome in four cases (6.6%) and wall atrophy in one case (1.7%) (Table 1). In the four cases with mass syndrome, the average maximum mass diameter was 61.5 mm (range 23–114), and no enhancement of the mass was evident at any phase. Wall atrophy affected the entire stomach and was only enhanced in the delayed phase.

Table 1 Types of radiological involvement (frequency per organ)
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Diffuse wall thickening was present in 46.7% of cases (n = 28/60) and involved the stomach, sigmoid, rectum, or anus. Segmental lesions were present in 45% of cases (n = 27/60) and involved the stomach, small intestine, or colon. The average lesion length was 64.4 mm (range 43–97), and the average lesion thickness was 15.1 mm (range 9–28.5).

Wall thickening affecting the entire stomach was present in 51.3% of cases (n = 20/39). Segmental involvement was generally antropyloric (84.2%, n = 16/19). Only one stenotic lesion was found in association with segmental wall thickening. No involvement beyond the serosa was observed.

When considering enhancement kinetics (Table 2), the following observations were made:

Table 2 Phase distributions in the assessed patients and lesions
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  • A total of 90.6% (n = 48/53) of the lesions assessed in the arterial phase showed early enhancement of the mucosal-submucosal complex.

  • A total of 93.2% (n = 55/59) of the lesions assessed in the delayed phase showed homogenous enhancement of the entire lesion, including all 55 cases with wall thickening.

  • The average variation in contrast enhancement between the pre-injection phase and the delayed phase was 70.8 HU (Table 3).

    Table 3 Densities before contrast injection and at the delayed portal post-equilibrium phase (2 min) and the difference between them
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Reader agreement

Satisfactory inter-reader agreement was found for the type of wall thickening (Kappa = 0.66), early enhancement (Kappa = 0.71), and delayed enhancement (Kappa = 0.87).

Discussion

Linitis plastica of the digestive tract is a particular form of gastrointestinal malignancy [2]. Histologically, it consists of tumor infiltration of the entire gut wall, fibrous stroma, and no distinct mass or obvious ulceration [3]. It is often discovered late and associated with peritoneal carcinomatosis [5, 11]. This diagnostic delay is due to the atypical nature of the associated clinical signs and symptoms [12] and to negative biopsy results on initial endoscopy (30% of cases of gastric linitis) [13]. Repeated deep biopsies are needed to reveal the presence of tumor cells.

Treatment of linitis plastica of the digestive tract is generally limited to surgery, which may or may not be curative, and/or palliative chemotherapy. The overall survival rates range from 0% to 21.8% at 5 years [11, 14], with a median survival time of 8–17 months [15].

CT is central to the positive diagnosis of gastric linitis, as it provides an earlier diagnosis than endoscopy (74.9% vs 44.1%) by revealing segmental or diffuse thickening of the stomach wall with contrast uptake [16]. Despite the importance of CT in this setting, the specific CT features associated with this malignancy have not previously been analyzed.

Gastrointestinal linitis affects similar numbers of men and women (51.1% and 48.9%, sex ratio = 1.04). The published results vary widely from one study to another, probably because of population differences and the varying forms of linitis [11, 17].

The average age at diagnosis was 63.2 years (range 31–86 years) in our study, in agreement with that reported by Otsuji et al. (57.9 years) [17]. In contrast, Kong et al. [18] reported that gastric linitis primarily occurred before age 45. It should be noted that our study focused on a Caucasian population and included all sites of involvement.

One unique feature of linitis plastica is that it may be primary or secondary. Secondary linitis was found in 26.7% of our cases. This proportion corresponds well with the 20% reported by Nguyen et al. [8]. Various histological types of cancer can give rise to secondary linitis, but breast and urothelial carcinomas appear to be the most common primary tumors [19]. Secondary linitis was synchronous in 56.3% of the cases in our study. Multiple sites of involvement (a maximum of three per patient in our series) must therefore be systematically identified.

All sections of the digestive tract can be involved [20], although we observed no cases of esophageal linitis. The two most common sites in our study were the stomach (68.3%) and rectum (11.7%) (Table 1).

Linitis plastica exhibits specific and similar CT features regardless of its location within the digestive tract. Wall thickening was observed in 91.7% of our cases. This thickening had a regular, concentric, and symmetrical appearance and reduced the caliber of the intestinal lumen. In our study, the average thickness of the involved walls was 15 mm, which was concordant with a previous report by Ha et al. [21]. This type of thickening rarely causes stenosis (with stenosis noted in only one case in our study).

Linitis plastica lesions can be diffuse and affect entire organ, which was the case in the sigmoid, rectum, and anus in our study. Alternatively, the lesions may be segmental, particularly in the small intestine and colon (the average lesion length was 64.4 mm in these two locations). Only the stomach showed both diffuse and segmental lesions [mainly of the pylorus and antrum (84.2%)].

Enhancement after contrast injection is particularly specific in this setting, as enhancement of the entire lesion was observed during the delayed phase in 93.2% of our cases, rising to 100% in the cases with wall thickening because the various wall layers and folds were no longer discernible. This delayed enhancement (at 2 min) concerned all wall layers and corresponded to tumor infiltration. This defining feature reflects the abundant stroma associated with linitis (Fig. 6). Infiltration by fibrous stroma also explains the initial lack of distension described in esophagogastroduodenal transit studies [6, 22]. This lack of distension reflects the loss of wall flexibility due to fibrous infiltration. However, this feature is difficult to assess by CT, as dynamic analyses cannot be performed. A loss of compliance is nonetheless a sign of diffuse gastric involvement.

Fig. 6
figure 6

Segmental gastric linitis. A contrast-enhanced CT scan (A) showing concentric cardiac wall thickening (arrows). White, regular thickening was macroscopically evident (B). Photomicrographs [×2.5 (C) and ×200 (D)] showing a diffuse, poorly differentiated adenocarcinoma (C) with signet ring cell morphology (D) affecting the entire wall

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The above CT features are evocative of linitis plastica and thus could rule out the most probable differential diagnoses. In particular, gastric involvement may suggest lymphoma. However, in the case of lymphoma, wall thickening is irregular and nodular [23] and some degree of gastric distensibility persists. In addition, there is no tumor enhancement due to the absence of stromal fibrosis [24]. Adenocarcinoma takes the form of a relatively ulcerated mass with heterogeneous contrast enhancement [25, 26], while endocrine and connective tissue tumors are more necrotic and show early enhancement. Metastases of the small intestine may be secondary to breast cancer, lung cancer, or melanoma [27], but the lesions are shorter, the thickening is less uniform, and the contrast uptake is more irregular [28].

Gastrointestinal wall thickening can also be observed in inflammatory and infectious diseases. However, in these settings, hypodense submucosal edema is observed after contrast injection, the different wall layers remain distinct [10, 28, 29], and there is no homogeneous wall enhancement on delayed images. Likewise, there is no loss of wall compliance or folds.

The main difficulty in diagnosing linitis plastica is distinguishing it from chronic inflammatory bowel disease (IBD), as fibrous components are present in both conditions. This distinction is particularly challenging, as malignant transformation is a common complication of IBD, and linitis is one of the forms this transformation can take [30]. Only biopsy or surgery to excise a specimen for histological examination can ensure the absence of underlying neoplasia.

The key limitation of our study is its retrospective, single-center design, which limited patient recruitment (only 46 patients). Our study focused only on a Caucasian population. The dynamic enhancement of the thickened wall during the portal phase is unknown due to our analysis. Furthermore, “linitis plastica” is a term that is typically used only on the endoscopic and macroscopic plane. We aimed to correlate the histological definition of this condition with its imaging features, which explains why we found four unexpected masses and an atrophied wall in our series. A prospective study including an analysis of wall enhancement in all cases with gastrointestinal wall involvement would provide additional valuable information.

In conclusion, linitis plastica can affect any segment of the digestive tract. It may be primary or secondary, with breast and urothelial carcinomas being the most common primary lesions in cases of secondary linitis plastica. Multiple lesion sites are rare and must be systematically identified. In cases with wall thickening without a mass syndrome, an appropriate CT protocol must be used, with both acquisitions prior to contrast injection and in the delayed phase (2 min after injection).

In summary, the CT features suggestive of gastrointestinal linitis include regular, concentric wall thickening and delayed (2 min), regular, homogeneous enhancement associated with losses of wall compliance and folds. The detection of these specific features should indicate the need for deep endoscopic biopsy where possible.