The aim of the present study was to analyze the clinicopathological characteristics presented in 9 cases of gastric calcifying fibrous tumor (CFT), and investigate the expressions and clinical implications of G protein-coupled estrogen receptor (GPER), estrogen receptor (ER) and vimentin in gastric CFTs. The clinical and pathological information of 9 patients with CFTs was investigated retrospectively. Subsequently, the expression of GPER, ER and vimentin were examined using immunohistochemistry, and a literature search for gastric CFT was conducted. The 9 patients were 40–71 years old with a mean age of 52.22 years, including 6 female and 3 male patients. Pathological features included dense hyalinized collagen fibers with a psammomatous body or dystrophic calcification, and the infiltration of scattered lymphocytes and plasma cells. Immunohistochemically, all cases expressed vimentin and GPER, whereas ER expression was negative. Using a database research, 25 studies regarding gastric CFT were identified, including 48 cases with a sex ratio (female:male) of 1.4:1. In addition, the number of female patients was twice the number of male patients in patients <50 years old, whereas the number was almost equal between women and men ≥50 years of age. Gastric CFT is a benign lesion with a good prognosis and a predilection for female patients, particularly premenopausal women. Estrogen may serve a role in this female predominance, and this may be mediated by GPER rather than ER.
Calcifying fibrous tumor (CFT) was first described as a ‘childhood fibrous tumor with psammoma bodies’ by Rosenthal and Abdul-Karim (
The clinical information, relevant biochemical indicators [blood routine, tumor markers, C reactive protein, hepatitis B virus and
Tumor specimens resected by endoscopic submucosal dissection (ESD) or gastric wedge excision (GWE) were fixed in 10% formalin solution for 4 h at room temperature and embedded in paraffin using routine methods. Deparaffinized sections with 4 µm thickness were used for staining with hematoxylin and eosin (5 min for hematoxylin and 1 min for eosin). Immunohistochemical techniques were conducted according to the SP method as described previously (
Six patients (cases 4–9) originally attended the hospital for a check-up for non-specific symptoms, such as belching or a bloated abdomen. Among the 9 cases, there were 6 female patients and 3 male patients (2:1). The age of the patients ranged from 40–71 years, with a mean age of 52.22 years. A total of 6 tumor cases (cases 1, 2, 5, 6, 7 and 8) originated from the gastric body, whereas the remaining 3 originated from the fundus of the stomach (cases 3, 4 and 9;
No abnormalities were evident in routine and tumor marker blood tests [including carcinoembryonic antigen, α-fetoprotein, carbohydrate antigen (CA)19-9 and CA-125]. Cases 1 and 2 presented with chronic hepatitis B virus (HBV) infection, and cases 1, 3 and 8 were positive in the 13C breath test and diagnosed with HP infection (
Sections from all 9 cases revealed well-defined lumps; each section contained an isolated nodular lesion covered by intact mucosa. The maximum diameter ranged from 1.3–2.5 cm, with a mean of 1.81 cm. A total of 4 tumors (cases 2, 3, 4 and 8) were located in the lamina propria, with extension to the submucosa, whereas the remaining 5 cases (1, 5, 6, 7 and 9) occurred in the submucosa (
Microscopically, the common characteristics of the 9 cases included considerable hypocellular sclerosis and wavy storiform coarse collagen infiltrated with scattered or patchy mononuclear inflammatory cells. Six cases (cases 1, 2, 4, 5, 6 and 9) exhibited a predominance of dense hyaline fibrous tissue infiltrated with many inflammatory cells and multifocal dystrophic calcifications. Psammomatous and dystrophic calcifications are indicated in
From the immunohistochemical examination of gastric CFT specimens, lesional cells were determined to be positive for vimentin and GPER expression. However, all 9 cases were negative for ER expression (
A total of 8 patients were treated with ESD; only 1 patient (case 6) underwent partial gastrectomy. Following ESD or surgical treatment, all patients recovered fully. None of the 9 patients available to follow-up (mean follow-up time, 13.11 months; range, 4–25 months) have experienced local recurrence (
In total, 25 previous studies regarding gastric CFT were identified, including 39 individual cases (
To the best of our knowledge, the present study reported the largest case series on gastric CFTs to date. Among the 9 gastric CFT patients included in this study, 3 were infected with HP, and 2 with HBV. Due to the extremely low incidence of this type of tumor, there is no previous research considering the association between the occurrence of gastric CFT and HP or HBV. In addition, the distribution of the 48 reported cases indicated that people from East Asia may be more likely to suffer from this disease compared with people from Europe or North America. Whether this is a coincidence requires further exploration.
At present, the etiology and pathogenesis of CFT confined to the gastric wall remain elusive (
The present study demonstrated that gastric CFT may have a female predominance (female:male, 2:1), which is consistent with the previous literature (1.27:1) (
As estrogen exerts its effects via binding GPER or ER, the ER and GPER expression status of the patient samples was detected with immunohistochemistry. Immunostaining was performed on samples from 9 cases; cells from the lesions exhibited positive immunoreactivity for GPER, but no immunoreactivity for ER. ER, also known as classical steroid receptor, is a ligand-activated nuclear transcription factor that recognizes cis-acting hormone response elements in the promoters of hormonally regulated genes (
Gastric CFT is a benign lesion with a good prognosis that demonstrates a predilection for female patients, especially premenopausal women. Estrogen mediated by GPER rather than ER may serve a role in this female predominance. The association between gastric CFTs and HP or HBV infection remains to be elucidated in high-calibrated studies.
Not applicable.
The present study was supported by grants from the National Natural Science Foundation of China (grant nos. 81372551 and 81602535).
The data generated during the present study are available from the corresponding author on reasonable request.
ST and WD conceived and designed the present study; XP performed the literature review; ZZ assessed the immunohistochemical results; ST wrote the manuscript. All authors read and approved the final manuscript.
The present study was approved by the Institutional Review Board of the Renmin Hospital of Wuhan University (Wuhan, China). All patients included in this study provided written informed consent.
Not applicable.
The authors declare that they have no competing interests.
Microscopic features of gastric calcifying fibrous tumor. (A) The mass was well-circumscribed and located in the lamina propria (H&E staining; original magnification, ×40). (B and C) Lymphoplasmacytic inflammatory infiltrate was present throughout the tumor and focally formed lymphoid follicles (H&E staining; B, original magnification, ×200; C, original magnification, ×100). (D) Psammoma and dystrophic bodies are visible in this case (H&E staining; original magnification, ×100). H&E, hematoxylin and eosin.
Immunohistochemical features of gastric calcifying fibrous tumor (hematoxylin and eosin staining; original magnification, ×200). (A) Vimentin expression was positive; (B) estrogen receptor expression was negative; (C) G protein-coupled estrogen receptor expression was positive. (D) Immunohistochemical negative control.
Age-sex distribution of all 48 reported gastric calcifying fibrous tumor cases. The number of female patients was twice that of male patients <50 years of age, whereas the number was almost equal between women and men ≥50 years of age.
Clinicopathologic features of 9 cases of gastric calcifying fibrous tumor.
Case no. | Age (years) | Sex | Smoking | Drinking | BMI (Kg/m2) | Concomitant disease | Site | Layer | Size (cm) | Treatment | Complications | Follow-up (months) |
---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | 44 | Female | No | No | 22.89 | Reflux esophagitis | Body | Submucosa | 1.5×1.0×0.8 | ESD | None | 25 |
2 | 50 | Female | No | No | 27.06 | Duodenal ulcer | Body | Lamina propria | 1.5×1.5×1.0 | ESD | Celialgia | 14 |
3 | 42 | Female | No | Yes | 23.81 | Erosive hemorrhagic gastritis hypertension | Fundus | Lamina propria | 1.3×0.8×0.6 | ESD | None | 23 |
4 | 61 | Male | Yes | Yes | 17.90 | None | Fundus | Lamina propria | 2.5×2.0×1.5 | ESD | None | 17 |
5 | 46 | Female | No | No | 21.33 | None | Body | Submucosa | 1.7×1.5×0.2 | ESD | None | 11 |
6 | 71 | Male | No | No | 20.24 | Diabetes | Body | Submucosa | 2.0×1.5×0.5 | GWE | Celialgia | 9 |
7 | 54 | Female | No | No | 23.44 | None | Body | Submucosa | 2.0×1.5×1.5 | ESD | None | 9 |
8 | 62 | Male | Yes | Yes | 27.34 (alcoholism) | Superficial gastritis | Body | Lamina propria | 2.0×1.2×0.4 | ESD | None | 6 |
9 | 40 | Female | No | No | 19.52 | Superficial gastritis | Fundus | Submucosa | 1.8×1.3×0.8 | ESD | None | 4 |
ESD, endoscopic submucosal dissection; GWE, gastric wedge excision; BMI, body mass index.
Laboratory tests of 9 cases of gastric calcifying fibrous tumor.
Case no. | Blood routine | Tumor markers |
CRP | HBV | HP |
---|---|---|---|---|---|
1 | – | – | ↑ | + | + |
2 | – | – | ↑ | + | N |
3 | – | – | ↑ | N | + |
4 | – | – | – | N | N |
5 | – | – | – | N | N |
6 | – | – | – | N | N |
7 | – | – | ↑ | N | N |
8 | – | – | ↑ | N | + |
9 | – | – | – | N | N |
Tumor markers consist of carbohydrate antigen 125, carbohydrate antigen 19-9, α-fetoprotein and carcinoembryonic antigen. CRP, C-reactive protein; HBV, hepatitis B virus; HP,
Clinicopathologic features of 39 cases of gastric calcifying fibrous tumor from previous studies.
Author | Case no. | Country | Age (years) | Sex | Site | Layer | Size (cm) | Treatment | (Refs.) |
---|---|---|---|---|---|---|---|---|---|
Tanaka |
10 | Japan | 43 | Female | NA | Submucosa | NA | Local excision | ( |
Liu and Song | 11 | China | 32 | Male | Body | Submucosa | 3.0×2.0×2.0 | Local excision | ( |
Nascimento |
12 | USA | 64 | Male | NA | NA | 1.1 | Local excision | ( |
Nascimento |
13 | USA | 65 | Female | NA | NA | 0.8 | Local excision | ( |
Kitamura |
14 | Japan | 44 | Female | Body | Submucosa | 3×2.6×2.4 | LWGR | ( |
Yun |
15 | Korea | 59 | Male | Fundus | Lamina propria | 3.9×2.7 | LWGR | ( |
Agaimy |
16 | Germany | 51 | Male | Body | Lamina propria | 2.0 | Local excision | ( |
Agaimy |
17 | Germany | 77 | Female | Body | Lamina propria | 1.0 | Local excision | ( |
Agaimy |
18 | Germany | 59 | Female | Body | Lamina propria | 3.0 | Local excision | ( |
Agaimy |
19 | Germany | 53 | Male | Antrum | Muscularis mucosae | 2.0 | Local excision | ( |
Agaimy |
20 | Germany | 40 | Male | Body | Lamina propria | 2.0 | Local excision | ( |
Agaimy |
21 | Germany | 42 | Female | Body | Lamina propria | 3.0 | Local excision | ( |
Agaimy |
22 | Germany | 51 | Male | Body | Lamina propria | 2.2 | Local excision | ( |
Pezhouh |
23 | USA | 70 | Female | NA | Submucosa | 1.3 | NA | ( |
Pezhouh |
24 | USA | 39 | Male | NA | Submucosa | 1.5 | NA | ( |
Pezhouh |
25 | USA | 51 | Female | NA | Serosa | 0.5 | NA | ( |
Pezhouh |
26 | USA | 40 | Female | NA | Submucosa | 2.5 | NA | ( |
Pezhouh |
27 | USA | 65 | Female | NA | Submucosa | 1.5 | NA | ( |
Shi |
28 | China | 58 | Female | Body | Lamina propria | 2.3 | ESD | ( |
Shi |
29 | China | 46 | Female | Body | Lamina propria | 1.0 | ESD | ( |
Shi |
30 | China | 61 | Male | Body | Lamina propria | 2.0 | EFR | ( |
Shi |
31 | China | 53 | Male | Antrum | Lamina propria | 2.5 | EFR | ( |
Fan |
32 | China | 49 | Male | Body | NA | 2.0×2.5 | Local excision | ( |
Ogasawara |
33 | Japan | 37 | Female | Body | Lamina propria | 1.0 | ESD | ( |
George and Abdeen | 34 | Kuwait | 27 | Female | Fundus | Submucosa | 1.5×1×0.5 | Surgery | ( |
Zhang |
35 | China | 55 | Female | Body | Submucosa | 2.0 | ESD | ( |
Vasilakaki |
36 | Greece | 60 | Male | Body | Lamina propria | 1.0×0.8 | Local excision | ( |
Attila |
37 | Canada | 47 | Female | Body | Mucosa | 2.0×2.0 | LWGR | ( |
Elpek |
38 | Turkey | 25 | Man | Body | Submucosa | 1×0.9×0.5 | Urgent surgery | ( |
Puccio |
39 | Italy | 49 | Female | Body | NA | NA | LWGR | ( |
Štofíková |
40 | Slovakia | 68 | Female | Body | Submucosa | 3.2 | Local excision | ( |
Abbadessa |
41 | USA | 17 | Male | NA | NA | NA | LWGR | ( |
Lee |
42 | Korea | 49 | Man | Body | Submucosa | 3.0 | Laparoscopic and endoscopic excision | ( |
Liu |
43 | China | 37 | Female | NA | NA | NA | Endoscopic resection | ( |
Lee |
44 | Korea | 5 | Female | Fundus/body | NA | 4.0×3.0 | Total excision | ( |
Delbecque |
45 | Switzerland | 63 | Male | Body | Submucosa | 2×1.5×1.5 | Local excision | ( |
Azam |
46 | Pakistan | 13 | Male | Fundus | NA | 8.0×6.0×6.0 | Surgery | ( |
Chatelain |
47 | France | 50 | Female | Body | NA | 2.0 | Local excision | ( |
Jang |
48 | Korea | 43 | Female | Body | Submucosa | 3.0×2.0 | LGWR | ( |
LWGR, laparoscopic gastric wedge resection; ESD, endoscopic submucosal dissection; EFR, endoscopic full thickness resection; NA, not available.