Diffuse gastric cancer: symptoms, diagnosis, stages, treatment and prognosis

Diffuse gastric cancer is not simply "disseminated gastric cancer," but a distinct histologic type of adenocarcinoma in which tumor cells grow scatteredly, poorly form glands, and can infiltrate the gastric wall without a distinct tumor mass. In the classic Lauren classification, gastric cancer is divided into intestinal, diffuse, mixed, and indeterminate types; the diffuse type is often associated with poorly adherent cells and a signet-ring cell pattern. [1]

The main clinical problem with diffuse gastric cancer is that it can grow for a long time within the stomach wall, barely forming a noticeable protruding nodule. Therefore, endoscopy sometimes reveals only thickened folds, poor gastric distension, wall rigidity, or small areas of altered mucosa, while the actual tumor volume turns out to be larger than it appears on the surface. [2]

An extreme form of this growth is called "linitis plastica," or "plastic linitis": the stomach becomes dense, poorly distensible, with a thickened wall, sometimes resembling a "skin bottle." This condition is more often associated with diffuse and signet-ring cell carcinoma, has a high risk of occult spread throughout the peritoneum, and usually requires particularly careful staging. [3]

Diffuse gastric cancer can be sporadic, meaning it occurs without a clear hereditary syndrome, or hereditary. Hereditary diffuse gastric cancer is most often associated with pathogenic variants of the CDH1 gene, and less commonly with the CTNNA1 gene. With this syndrome, the risk of cancer can be high, and endoscopy does not always reliably detect early microscopic lesions. [4]

Modern treatment depends not only on the tumor stage but also on its molecular profile. In advanced gastric cancer, markers currently assessed include human epidermal growth factor receptor 2, programmed death protein 1 and its ligand, DNA mismatch repair deficiency, microsatellite instability, claudin 18.2, and other markers, as they influence the choice of immunotherapy and targeted therapy. [5]

The key question	Short answer
What does "diffuse" mean?	Tumor cells grow scatteredly and infiltrate the stomach wall
This is the same as stage 4	No, it's a histological type, not a stage.
A common cell variant	Signet ring cells and loosely adherent cells
Why is it difficult to diagnose?	The tumor may be under the mucosa and not form an obvious nodule.
Special form	Linitisplasty with a dense rigid gastric wall
Hereditary form	Often associated with the CDH1 gene
What is important for treatment	Stage, operability, biomarkers and general condition of the patient

Code according to ICD 10 and ICD 11

In the International Classification of Diseases, 10th revision, diffuse gastric cancer is typically coded as a malignant neoplasm of the stomach under category C16, with anatomical location specified: cardia, fundus, body, antrum, pylorus, lesser or greater curvature, overlying lesion, or unspecified location. A separate code specifically for the "diffuse type" is not typically used in this system, so the histological type is indicated separately in the pathological diagnosis. [6]

In the International Classification of Diseases, 11th revision, malignant neoplasms of the stomach are classified under 2B72, and gastric adenocarcinoma is coded 2B72.0. Additional genetic and syndromic specifications may be used for hereditary diffuse gastric cancer, but the basic oncology code depends on what is being coded: the tumor itself, the hereditary syndrome, or the risk condition. [7]

The code does not replace a full diagnosis. For the physician, the full formulation is more important: "gastric adenocarcinoma of the diffuse type," "poorly adherent carcinoma," "signet ring cell carcinoma," "linitis plastica," anatomical site, depth of invasion, lymph node involvement, presence of metastases, and molecular markers. [8]

In hereditary diffuse gastric cancer, the medical records additionally indicate the detected pathogenic gene variant, most often CDH1, less often CTNNA1, family history, the results of genetic counseling, and the chosen tactics: prophylactic gastrectomy or endoscopic observation in carefully selected patients. [9]

System	Code or heading	What does it mean?	Comment
ICD 10	C16	Malignant neoplasm of the stomach	Basic heading
ICD 10	C16.0	Malignant neoplasm of the cardia	In case of damage to the entrance area of the stomach
ICD 10	C16.2	Malignant neoplasm of the body of the stomach	One of the common localization options
ICD 10	C16.3	Malignant neoplasm of the antrum	Anatomy Code
ICD 10	C16.8	Overlapping lesion of the stomach	When the tumor affects several areas
ICD 11	2B72	Malignant neoplasms of the stomach	Main section
ICD 11	2B72.0	Gastric adenocarcinoma	The closest code for diffuse adenocarcinoma

Epidemiology

Gastric cancer remains one of the leading causes of cancer-related deaths worldwide. According to the Global Cancer Observatory of the International Agency for Research on Cancer, in 2022, there were 968,784 new cases of gastric cancer and approximately 660,175 deaths, making it the fifth most common cancer in terms of incidence and mortality. [10]

The prevalence of stomach cancer varies greatly by region. Higher rates are observed in East Asia, parts of Eastern Europe, and some regions of Latin America, while in low-incidence countries, mass screening generally does not provide the same benefit as in high-risk countries.[11]

The diffuse type accounts for a smaller proportion of all gastric adenocarcinomas than the intestinal type, but is of particular clinical significance due to its more insidious growth, high probability of late detection, and tendency to spread throughout the peritoneum. The exact proportion depends on age, gender, region, pathological evaluation criteria, and the inclusion of signet-ring cell tumors. [12]

Unlike the intestinal type, which is more often associated with chronic atrophic gastritis, intestinal metaplasia, and a prolonged cascade of precancerous changes, the diffuse type can occur without a clearly visible precancerous background. This is one of the reasons why it is more difficult to detect early with conventional surveillance strategies. [13]

Hereditary diffuse gastric cancer is rare, but is of great importance for families with a history of diffuse gastric cancer at a young age or a combination of diffuse gastric cancer and lobular breast cancer. The National Cancer Institute of the United States recommends that genetic testing for hereditary CDH1 syndrome be performed according to the criteria of the International Gastric Cancer Linkage Consortium. [14]

Indicator	What is known
New cases of stomach cancer worldwide in 2022	968 784
Stomach cancer deaths worldwide in 2022	About 660,175
Place among cancers by incidence	5th place
Rank among cancers by mortality rate	5th place
Diffuse type	A smaller but clinically important proportion
Hereditary diffuse gastric cancer	Rare, but requires a family approach
The main epidemiological feature	Large regional differences

Reasons

The causes of diffuse gastric cancer are multifactorial: genetic changes, disruptions in intercellular adhesion, mucosal inflammation, external carcinogenic factors, and family risk factors are all involved. For the diffuse type, loss of normal function of the molecules that hold cells together is particularly important, making it easier for tumor cells to disperse within the stomach wall. [15]

In some patients, the CDH1 gene, encoding the protein E-cadherin, plays a key role. This protein helps epithelial cells adhere to each other; when its function is impaired, the cells become less cohesive, consistent with the biology of diffuse growth and signet-ring cell lesions. [16]

Helicobacter pylori remains the leading carcinogen for gastric cancer overall. In 2026, the International Agency for Research on Cancer reiterated that Helicobacter pylori infection is the leading cause of gastric cancer, and that treatment of the infection reduces gastric cancer incidence by 36% and mortality by 22% in pooled data from randomized trials. [17]

However, the association between Helicobacter pylori and the intestinal type of gastric cancer and the cascade of atrophy, metaplasia, and dysplasia is particularly strong; for the diffuse type, this association is more complex and does not explain all cases. Therefore, in a patient with diffuse gastric cancer, the cause cannot be reduced to infection alone or to heredity alone. [18]

Additional risk factors and conditions include smoking, high intake of salted, smoked and poorly preserved foods, low intake of fruits and vegetables, previous radiation exposure, family history, certain hereditary syndromes and chronic diseases of the gastric mucosa.[19]

Cause or mechanism	Meaning
Violation of intercellular adhesion	Supports diffuse infiltrative growth
Pathogenic CDH1 variants	The main hereditary cause
Pathogenic variants of CTNNA1	A rarer hereditary factor
Helicobacter pylori	The main risk factor for stomach cancer in general
Smoking	Increases the risk of stomach cancer
Salted and smoked foods	Associated with increased risk
Family history	Requires a hereditary risk assessment

Risk factors

Family history is particularly important for diffuse gastric cancer. If there are cases of diffuse gastric cancer in the family, especially at a young age, or a combination of diffuse gastric cancer and lobular breast cancer, a consultation with a medical geneticist is necessary. [20]

Pathogenic variants of CDH1 are considered the most prominent cause of hereditary diffuse gastric cancer. In carriers of these variants, standard endoscopy may miss microscopic lesions, so international guidelines recommend prophylactic gastrectomy as the primary way to dramatically reduce the risk of cancer in eligible patients. [21]

Helicobacter pylori infection is the most important modifiable risk factor for gastric cancer. Even if it does not explain every case of diffuse gastric cancer, its detection and eradication in those with indications remains part of gastric cancer prevention and treatment of precancerous mucosal lesions. [22]

Smoking increases the risk of stomach cancer and simultaneously worsens overall health, treatment tolerance, and cardiovascular risk. Therefore, quitting smoking is important not only for prevention but also for preparation for surgery, chemotherapy, and post-treatment recovery. [23]

Age, male gender, living in a region with a high incidence, family history of gastric cancer, low intake of vegetables and fruits, excess salty foods, chronic atrophic gastritis and intestinal metaplasia increase the overall risk of gastric cancer, although not all of these factors are equally specific to the diffuse type.[24]

Risk factor	For whom is it especially important?
Familial cases of diffuse gastric cancer	For genetic counseling
Pathogenic CDH1 variant	For prophylactic gastrectomy or observation
Helicobacter pylori	For the prevention of stomach cancer in general
Smoking	For prevention and better tolerability of treatment
Salted and smoked foods	For long-term risk reduction
Lobular breast cancer in the family	To evaluate a hereditary syndrome
Young age at stomach cancer	To search for a hereditary cause

Pathogenesis

The pathogenesis of diffuse gastric cancer is associated with the loss of normal epithelial architecture. Tumor cells are poorly connected to each other, so they do not form distinct glandular structures, but spread along the stomach wall as individual cells or small groups. [25]

Signet ring cells are named for their characteristic appearance under a microscope: mucus pushes the nucleus to the periphery, resembling a signet ring. The presence of these cells is often associated with the diffuse type, but the final assessment always rests with the pathologist, who describes the percentage, depth of invasion, and other tumor features. [26]

In linitis plasty, tumor cells infiltrate the stomach wall, causing it to become thickened, dense, and poorly distensible. The mucosal surface may appear less dramatic than the true depth of the lesion, so routine superficial biopsies sometimes provide a false sense of security. [27]

Diffuse cancer tends to spread peritoneally, affecting the peritoneum and omentum and causing ascites. Therefore, in potentially resectable cases, staging often includes not only computed tomography but also diagnostic laparoscopy in patients with a high risk of occult peritoneal metastases. [28]

Molecularly, diffuse gastric cancer is heterogeneous. Some tumors exhibit CDH1 alterations, some express claudin 18.2, and some express other targets. This is why modern treatment strategies for advanced gastric cancer are increasingly based on biomarker testing, rather than just the microscopic type. [29]

Pathogenetic mechanism	What does this mean?
Loss of cell cohesion	Scattered growth without a clear tumor mass
Signet ring cells	Frequent microscopic component
Infiltration of the gastric wall	Thickening and rigidity of the wall
Linitis plastica	A dense, poorly distensible stomach
Peritoneal spread	Risk of occult peritoneal metastases
Molecular heterogeneity	Biomarkers are needed to select treatment

Symptoms

In its early stages, diffuse gastric cancer may not cause obvious symptoms. Dyspepsia, upper abdominal discomfort, early satiety, loss of appetite, mild nausea, bloating after eating, and heartburn are possible, but these symptoms are often similar to functional dyspepsia, gastritis, or reflux disease. [30]

As the tumor grows, more worrisome signs appear: unexplained weight loss, persistent pain in the upper abdomen, vomiting, rapid satiety on small amounts of food, weakness, anemia, blood in the stool, black stool, progressive loss of appetite and inability to eat normally.[31]

The diffuse type is particularly characterized by a feeling of early satiety and heaviness after a small portion, because the infiltrated stomach wall is less elastic. With linitis plasty, the stomach loses elasticity, and the patient may feel that "the food doesn't fit," although there is no obvious mechanical obstruction in the early stages. [32]

If the tumor is located closer to the esophagogastric junction, difficulty swallowing may occur. If the gastric outlet is affected, repeated vomiting, a feeling of fullness, dehydration, and malnutrition due to obstructed food passage are possible. [33]

As the tumor spreads through the peritoneum, abdominal distension due to ascites, pain, intestinal obstruction, severe weakness, and rapid deterioration of general condition may occur. These symptoms usually indicate a late stage and require urgent oncological evaluation. [34]

Symptom	Why is it important?
Early saturation	May reflect poor gastric compliance
Weight loss	An alarming oncological sign
Anemia	It may be a consequence of hidden bleeding or nutritional disorders.
Black chair	Possible bleeding from the upper gastrointestinal tract
Vomit	Possible disruption of food passage
Ascites	Possible peritoneal spread
Difficulty swallowing	Possible damage to the gastric inlet area

Classification, forms and stages

According to the Lauren classification, gastric cancer is divided into intestinal, diffuse, mixed, and indeterminate types. The intestinal type more often forms glandular structures and is associated with a precancerous cascade, while the diffuse type is characterized by poorly adherent cells, poor gland formation, and infiltrative growth. [35]

According to the World Health Organization classification, the diffuse type is related to a group of poorly linked carcinomas, including signet-ring cell carcinoma. It is important to understand that "signet-ring cell" and "diffuse" are closely related, but not always completely identical, terms: one describes the cellular appearance, the other the histological growth pattern. [36]

Based on clinical presentation, tumors are classified as limited, infiltrative, and linitis plastica. Linitis plastica is the most diffuse form, affecting a significant portion of the stomach, with the wall becoming thickened and poorly distensible, and the risk of underestimating its prevalence is particularly high. [37]

Staging is performed using a "tumor, lymph nodes, metastases" system: the depth of tumor invasion into the stomach wall, the involvement of regional lymph nodes, and the presence of distant metastases are assessed. The stage determines whether the disease can be treated curatively or whether it is primarily aimed at controlling a widespread process. [38]

From a practical standpoint, stages can be divided into early cancer, locally advanced resectable cancer, locally advanced inoperable cancer, and metastatic cancer. The diffuse type can occur at any stage, but most often causes diagnostic difficulties due to its infiltrative growth. [39]

Classification principle	Options
According to Lauren	Intestinal, diffuse, mixed, unspecified
By cellular structure	Poorly linked carcinoma, signet ring cell carcinoma
By growth form	Limited, infiltrative, linitisplasty
By stage	Early, locally advanced, metastatic
By operability	Resectable, borderline, unresectable
By biomarkers	With expression of human epidermal growth factor receptor 2, claudin 18.2, microsatellite instability and other features
By heredity	Sporadic and hereditary form

Complications and consequences

Diffuse gastric cancer can cause chronic or acute bleeding. The patient may notice black stools, weakness, dizziness, anemia, or decreased hemoglobin without an obvious cause; sometimes, bleeding is hidden and is only detected by tests. [40]

The second complication is malnutrition. Due to early satiety, nausea, vomiting, pain, and decreased food intake, a person loses weight, muscle tissue, and strength, which impairs tolerance to surgery, chemotherapy, and immunotherapy. [41]

The third complication is stenosis or obstruction of food passage. If the tumor affects the gastric outlet, food may be retained, leading to vomiting of ingested food, dehydration, electrolyte imbalances, and the need for emergency care. [42]

The fourth complication is peritoneal carcinomatosis, or tumor spread throughout the peritoneum. This is especially important for diffuse and signet-ring cell carcinoma, as peritoneal metastases may be difficult to see on early imaging, but they dramatically alter the prognosis and treatment plan. [43]

The fifth consequence is the hereditary risk for relatives if hereditary diffuse gastric cancer syndrome is detected. In this case, the diagnosis of one patient becomes the reason for genetic counseling for the family, as prevention can save the lives of carrier relatives. [44]

Complication	How does it manifest itself?
Bleeding	Anemia, black stool, weakness
Eating disorder	Weight loss, sarcopenia, deficiencies
Stenosis of the outlet	Vomiting, dehydration, inability to eat
Peritoneal metastases	Ascites, pain, intestinal obstruction
Pain	Invasion of the wall, peritoneum or neural structures
Psychological stress	Anxiety, depression, fear of food and treatment
Hereditary consequences	The need for examination of relatives

When to see a doctor

You should consult a doctor if you experience new or persistent upper abdominal symptoms that persist, recur, or worsen: early satiety, loss of appetite, nausea, pain, unexplained weakness, heartburn, or discomfort after eating. It is especially important to promptly seek medical attention for older adults and those with a family history of stomach cancer. [45]

Urgent evaluation is necessary if any of the following "red flags" are present: unexplained weight loss, anemia, black stools, vomiting blood, repeated vomiting, difficulty swallowing, progressive pain, rapid satiety with very little food, and persistent weakness. These signs do not prove cancer, but they do require ruling out a serious cause. [46]

If a person has relatives with diffuse gastric cancer, especially at a young age, or has a family history of diffuse gastric cancer and lobular breast cancer, genetic counseling should be sought. This is important even in the absence of symptoms, because hereditary risk sometimes manifests as microscopic lesions that are difficult to detect endoscopically. [47]

After treatment for Helicobacter pylori or chronic gastritis, one should not assume that the risk has completely disappeared. If alarming symptoms persist, an endoscopy with biopsy is necessary, as gastric cancer can masquerade as ordinary dyspepsia. [48]

If diffuse gastric cancer has already been diagnosed, it's important to seek referral to a specialized oncology center without delay. Treatment should be planned multidisciplinary: by a surgeon, oncologist, gastroenterologist, pathologist, radiologist, geneticist, and nutritionist. [49]

Reason for appeal	Why is it important?
Weight loss	A possible sign of an oncological process
Anemia	It may be a consequence of hidden bleeding.
Black chair	Possible bleeding from the stomach
Early saturation	Possible infiltration of the gastric wall
Vomit	Possible disruption of food passage
Family history of diffuse cancer	Indication for genetic evaluation
Lobular breast cancer in the family	Possible link to CDH1

Diagnostics

The first step is a clinical assessment: the doctor clarifies the symptoms, duration, weight loss, nature of pain, presence of vomiting, black stools, anemia, family history, previous Helicobacter pylori infection, stomach surgery, and medications. This stage does not establish a diagnosis, but determines the urgency and scope of the examination. [50]

The second step is esophagogastroduodenoscopy, which is an endoscopic examination of the esophagus, stomach, and duodenum. If stomach cancer is suspected, endoscopy should be accompanied by multiple biopsies, as visual examination alone is not sufficient. [51]

The European Society for Medical Oncology recommends that diagnosis be based on multiple endoscopic biopsies, typically 5-8 samples, to obtain a sufficient representation of the tumor. This is especially important in the diffuse type, where superficial mucosal lesions may not reflect the underlying lesion. [52]

The third step is pathological examination. The pathologist determines whether the tumor is adenocarcinoma, whether it is of the diffuse type, whether there are signet ring cells, how poorly differentiated the tumor is, and whether there is enough material for molecular testing. [53]

The fourth step is staging using computed tomography of the chest, abdomen, and pelvis, and in certain situations, endoscopic ultrasound, positron emission tomography, magnetic resonance imaging, or diagnostic laparoscopy. The goal of staging is to determine whether the tumor can be removed radically and whether there are hidden metastases. [54]

The fifth step is biomarker testing. In advanced or recurrent gastric cancer, biomarker testing is performed for human epidermal growth factor receptor 2, programmed death protein 1 (PDP-1) or its combined positivity, DNA mismatch repair deficiency, microsatellite instability, claudin 18.2, and other markers that may open the door to targeted therapy or immunotherapy. [55]

Diagnostic step	What are they doing?	For what
1	Symptom and risk assessment	Determine the urgency of the examination
2	Endoscopy	See the stomach from the inside
3	Multiple biopsies	Confirm cancer and reduce the risk of missing
4	Pathomorphology	Identify diffuse type and signet ring cells
5	Computed tomography	Estimate the spread
6	Diagnostic laparoscopy	Find hidden peritoneal metastases
7	Biomarkers	Select drug therapy

Differential diagnosis

Diffuse gastric cancer must be distinguished from chronic gastritis, functional dyspepsia, and peptic ulcer disease. These conditions can cause pain, heaviness, nausea, heartburn, and loss of appetite, but if there are alarming signs, anemia, weight loss, or persistent disease, endoscopy with biopsy is necessary. [56]

Linitisplasty must be distinguished from other causes of gastric wall thickening. Similar findings can include gastric lymphoma, gastric metastases, severe inflammatory diseases, infiltrative processes, and rare benign conditions, so imaging alone is usually insufficient. [57]

Signet-ring cell tumor of the stomach sometimes needs to be differentiated from gastric metastases, especially in women with lobular breast cancer. Lobular breast cancer can produce infiltrative metastases in the stomach, so pathology and immunohistochemistry are crucial. [58]

It is also important to distinguish primary gastric cancer from tumors of the gastroesophageal junction, neuroendocrine tumors, gastrointestinal stromal tumors, and lymphomas. These diseases have different treatment regimens, different biomarkers, and different surgical approaches. [59]

Hereditary diffuse gastric cancer must be distinguished from familial clusters of common gastric cancer without a detected pathogenic variant of CDH1 or CTNNA1. In both cases, the family may require surveillance, but the strategy of prophylactic gastrectomy and genetic testing depends on strict criteria. [60]

What is it compared to?	How to distinguish
Gastritis	Endoscopy, biopsy, no tumor cells
Peptic ulcer disease	Biopsy of ulcer edges and monitoring of healing
Gastric lymphoma	Pathomorphology and immunohistochemistry
Metastasis to the stomach	History of other tumors and special markers
Stromal tumor	Different cell type and different markers
Esophagogastric junction cancer	Anatomical localization
Hereditary syndrome	Genetic testing and family criteria

Treatment

Treatment of diffuse gastric cancer begins with proper staging and discussion at a multidisciplinary meeting. It is important to understand in advance whether the tumor can be radically resected, whether there are hidden peritoneal metastases, the patient's general condition, whether there is significant weight loss, and what biomarkers are available to guide drug therapy. [61]

Endoscopic resection is sometimes possible for early gastric cancer, but this approach is used much more cautiously for diffuse and signet-ring cell types. This is because diffuse tumors tend to grow infiltratively and may have a higher risk of underestimating the depth of the lesion and lymphatic spread, so standard surgery often remains a more reliable option. [62]

The primary radical treatment for operable diffuse gastric cancer is surgical removal of part or all of the stomach and its lymph nodes. The extent of the surgery depends on the location and extent of the tumor: distal gastrectomy, total gastrectomy, or extended surgery may be performed if necessary to achieve clean resection margins. [63]

For locally advanced, operable gastric cancer, perioperative chemotherapy—treatment before and after surgery—is often used. Its goal is to reduce tumor mass, eliminate micrometastases, increase the likelihood of radical surgery, and reduce the risk of recurrence. [64]

Some current perioperative chemotherapy options for suitable patients include fluorouracil, leucovorin, oxaliplatin, and docetaxel. However, in diffuse and signet-ring cell carcinoma, the effectiveness of chemotherapy may be less predictable, so the decision should take into account stage, age, nutrition, comorbidities, and the opinion of the expert team. [65]

Postoperative treatment depends on the preoperative course of treatment, the final stage, the quality of lymph node dissection, the resection margins, and the patient's condition. In some cases, postoperative chemotherapy is continued, while in others, chemoradiation or observation are considered, but there is no universal regimen for all patients with diffuse type disease. [66]

For inoperable locally advanced or metastatic gastric cancer, treatment is usually systemic. Chemotherapy, immunotherapy, targeted therapy, and palliative treatments are used to control symptoms, such as bleeding, stenosis, pain, nausea, ascites, and malnutrition. [67]

If the tumor is negative for human epidermal growth factor receptor 2 and expresses claudin 18.2, zolbetuximab in combination with fluoropyrimidine-platinum-based chemotherapy has been approved in the United States since October 2024 for the first-line treatment of locally advanced unresectable or metastatic adenocarcinoma of the stomach or gastroesophageal junction.[68]

If the tumor expresses human epidermal growth factor receptor 2, drugs targeting this receptor may be used, such as trastuzumab in first-line therapy in appropriate patients and trastuzumab deruxtecan in subsequent lines when indicated. The National Cancer Institute lists trastuzumab and trastuzumab deruxtecan among targeted agents used in gastric cancer. [69]

Immunotherapy is used in some patients with advanced gastric cancer, particularly if the tumor has high levels of microsatellite instability, a deficiency in the DNA mismatch repair system, or high expression of programmed death protein 1 and its ligand. The National Cancer Institute lists nivolumab and pembrolizumab among the immunotherapeutic agents used in gastric cancer. [70]

Palliative care does not mean abandoning treatment. It includes management of pain, nausea, vomiting, nutrition, anemia, ascites, anxiety, depression, and side effects of therapy; in diffuse gastric cancer, early involvement of nutrition and palliative care specialists is often critical to quality of life. [71]

Clinical situation	Basic tactics
Very early, low-risk cancer	Sometimes endoscopic resection, but with the diffuse type, carefully
Operable cancer	Gastrectomy or resection with lymph nodes
Locally advanced cancer	Perioperative chemotherapy and surgery
Peritoneal lesion	Systemic treatment and palliative care
Human epidermal growth factor receptor 2 positive cancer	Therapy against this receptor
Claudin 18.2 positive cancer	Zolbetuximab with chemotherapy in eligible patients
High microsatellite instability	Immunotherapy may be particularly important

Prevention

Prevention of gastric cancer generally begins with detection and treatment of Helicobacter pylori in individuals with indications. In 2026, the International Agency for Research on Cancer emphasized that "detection and treatment" programs for Helicobacter pylori could be an important tool for gastric cancer prevention, particularly in high-risk regions. [72]

Diet also plays a role: reducing the consumption of highly salted, smoked, and poorly preserved foods, quitting smoking, moderating alcohol consumption, eating enough fruits and vegetables, and controlling body weight are all general measures to reduce the risk of stomach cancer. These measures do not guarantee protection against the diffuse type, but they do reduce the overall carcinogenic background. [73]

For people with a pathogenic CDH1 variant, prophylaxis is of a different magnitude. The National Cancer Institute indicates that prophylactic total gastrectomy is generally considered the preferred strategy in patients with hereditary diffuse gastric cancer, as endoscopy may not reliably detect precancerous microscopic lesions. [74]

If prophylactic gastrectomy is delayed or not performed, an endoscopic surveillance program at an expert center is possible. However, the patient should understand the limitations: in hereditary diffuse gastric cancer, endoscopy reduces uncertainty but does not eliminate the risk of missing microscopic lesions. [75]

Prevention for relatives includes genetic counseling, review of testing criteria, discussion of the age to begin surveillance, informed decision-making about genetic testing, and psychological support. This is especially important because the decision to undergo prophylactic gastrectomy is difficult and has lifelong nutritional implications. [76]

Preventive measure	For whom is it important?
Detection and treatment of Helicobacter pylori	People with indications and high-risk regions
Quitting smoking	All risk groups
Reduce salty and smoked foods	General prevention
Genetic counseling	Families with diffuse gastric cancer
CDH1 and CTNNA1 testing	When the criteria are met
Prophylactic gastrectomy	High-risk carriers after consultation
Endoscopic observation	When an operation is pending or not selected

Forecast

The prognosis for diffuse gastric cancer depends primarily on the stage at diagnosis. If the tumor is detected very early and removed radically, the chances are significantly higher; if the lymph nodes, peritoneum, or distant organs are affected, the prognosis becomes worse. [77]

The diffuse type often has a worse prognosis than some intestinal forms, especially if it is diagnosed late, is accompanied by linitis plastica, signet-ring cell morphology, or peritoneal dissemination. However, the prognosis of a specific patient cannot be determined solely by the word "diffuse": stage, resection margins, lymph nodes, biomarkers, and response to treatment are important. [78]

Peritoneal metastases significantly worsen the prognosis because they are often poorly amenable to radical surgical treatment and can cause ascites, pain, intestinal obstruction, and malnutrition. Therefore, diagnostic laparoscopy in high-risk patients can prevent unnecessary major surgery if occult spread has already occurred. [79]

Molecular markers are gradually changing the prognosis of individual subgroups. The advent of immunotherapy, anti-human epidermal growth factor receptor 2 therapy, and anti-claudin 18.2 therapy have expanded treatment options for advanced gastric cancer, but these treatments are not suitable for everyone and require marker confirmation. [80]

After successful treatment, monitoring is necessary: monitoring nutrition, deficiencies, body weight, symptoms of relapse, surgical complications, and side effects of drug therapy. After gastrectomy, a person needs a long-term nutrition plan, vitamin B12 supplementation, iron, calcium, and vitamin D levels, and prevention of dumping syndrome. [81]

Forecast factor	How does it affect
Early stage	Best chances of recovery
Lymph node involvement	Increases the risk of relapse
Metastases in the peritoneum	Significantly worsen the prognosis
Linitis plastica	Often associated with a more complex course
Radicality of the operation	Clean edges improve prospects
Biomarkers	May open access to targeted therapy
Nutrition and general condition	Affect the tolerability of treatment

Frequently asked questions

Is diffuse gastric cancer always stage 4? No. The word "diffuse" describes the histologic type and growth pattern, not the stage. Diffuse cancer can be early, locally advanced, or metastatic; the stage is determined by the depth of invasion, lymph nodes, and metastases. [82]

Why is diffuse gastric cancer difficult to detect? It can grow diffusely within the gastric wall, without a clear nodule on the mucosal surface. Therefore, multiple biopsies, careful endoscopic assessment of gastric distensibility, and staging based on the risk of occult spread are necessary. [83]

What is signet ring cell gastric cancer? It is a type of tumor in which the cells contain a lot of mucus and resemble a signet ring under a microscope. This cell type is often associated with diffuse growth, but the final diagnosis is made by a pathologist. [84]

What is linitis plastica? It is an infiltrative form in which the gastric wall becomes dense, thickened, and poorly distensible. It is often associated with diffuse cancer and requires particularly careful staging, including assessment of the risk of peritoneal metastases. [85]

Is a complete gastrectomy always necessary? No, the extent of the surgery depends on the location and extent of the tumor. However, in cases of diffuse growth, multiple lesions, or a hereditary syndrome, total gastrectomy may be considered more often than in cases of limited intestinal disease. [86]

Is it possible to cure diffuse gastric cancer without surgery? If the cancer is resectable and there are no metastases, surgery is usually the central part of treatment with the goal of cure. In metastatic disease, systemic therapy and palliative care often become the mainstay. [87]

What biomarker tests are needed? In advanced cancer, human epidermal growth factor receptor 2, programmed death protein 1 and its ligand expression, microsatellite instability, DNA mismatch repair deficiency, claudin 18.2, and sometimes other targets are typically assessed. [88]

Should relatives be screened? Yes, if there is a suspicion of hereditary diffuse gastric cancer: cases of diffuse cancer in the family, young age at diagnosis, or a combination with lobular breast cancer. In such a situation, genetic counseling is necessary, not a random endoscopy without a plan. [89]

Does Helicobacter pylori treatment help? Helicobacter pylori treatment reduces the overall risk of stomach cancer and is an important preventative measure, especially in high-risk groups. However, it does not eliminate the inherited risk of CDH1 and does not replace screening for warning signs. [90]

Question	Short answer
Diffuse type is equal to the late stage	No
Main diagnostics	Endoscopy with multiple biopsies
The main risk	Hidden infiltrative and peritoneal growth
The main treatment for operability	Surgery plus systemic therapy as indicated
New drugs	Immunotherapy and targeted drugs based on biomarkers
Hereditary form	More commonly associated with CDH1
Prevention in CDH1 carriers	Genetic counseling and discussion of prophylactic gastrectomy

Key points from experts

Hans Prenen, Professor of Medical Oncology at the University of Antwerp and one of the authors of the European Society for Medical Oncology guidelines on gastric cancer, says: "The main practical thesis of current European guidelines is that gastric cancer treatment should be based on stage, operability, molecular markers, and discussion by a multidisciplinary team." [91]

Kohei Shitara, MD, an oncologist at the National Cancer Center Hospital East in Japan, is a leading researcher in drug treatment for gastric cancer. His clinical research is important to current practice because research on immunotherapy and targeted therapy has transformed the treatment of advanced gastric cancer, particularly in the presence of biomarkers. [92]

Vivian E. Strong, a surgeon at Memorial Sloan Kettering Cancer Center and a participant in international work on hereditary diffuse gastric cancer, said: "The key message of these recommendations is that in carriers of pathogenic CDH1 variants, prophylactic gastrectomy is often the most reliable risk-reduction strategy because early lesions are difficult to consistently detect endoscopically. [93]

Carla Oliveira, a professor and researcher in hereditary diffuse gastric cancer, is one of the authors of the international CDH1 guidelines. Her research emphasizes that hereditary diffuse gastric cancer is not only stomach cancer but also a familial syndrome that requires genetic counseling, testing of relatives, and discussion of the risk of lobular breast cancer. [94]

The Japanese Gastric Cancer Association's guidelines emphasize the central role of radical gastrectomy with adequate lymph node dissection for resectable gastric cancer and careful patient selection for endoscopic treatment of early tumors. [95]

The World Health Organization's International Agency for Research on Cancer. Its key prevention message: Helicobacter pylori is the leading cause of stomach cancer worldwide, and programs to detect and treat the infection can significantly reduce future morbidity and mortality. [96]

Expert source	The main practical conclusion
European Society for Medical Oncology	Staging, biomarkers and a multidisciplinary solution are needed
National Cancer Institute of the United States	Treatment depends on the stage and may include surgery, chemotherapy, immunotherapy, and targeted therapy.
Japan Gastric Cancer Association	Surgery with lymph node dissection remains the mainstay of curative treatment.
International guidelines for hereditary diffuse gastric cancer	CDH1 requires a genetic and preventive approach
United States Food and Drug Administration	Zolbetuximab opens a new avenue for the treatment of claudin 18.2-positive cancer
International Agency for Research on Cancer	Helicobacter pylori is a key target for prevention

Result

Diffuse gastric cancer is a specific histological type of adenocarcinoma, in which tumor cells grow in a scattered manner and infiltrate the gastric wall. It can present nonspecifically, masquerade as dyspepsia for a long time, and be more difficult to detect with conventional endoscopy, especially with linitisplasty. [97]

Diagnosis requires endoscopy with multiple biopsies, pathological confirmation, imaging staging, assessment of the risk of occult peritoneal metastases, and molecular testing. If a hereditary variant is suspected, consultation with a medical geneticist is necessary. [98]

Treatment depends on the stage: for operable disease, radical surgery with lymph nodes and systemic therapy as indicated is the basis; for advanced disease, chemotherapy, immunotherapy, targeted therapy, and palliative care are the mainstays. New drugs, including zolbetuximab for claudin 18.2-positive tumors, make biomarker testing a mandatory part of modern management. [99]

Prevention includes Helicobacter pylori control, smoking cessation, dietary modification, and, in high-risk families, genetic counseling. For carriers of pathogenic CDH1 variants, prophylactic gastrectomy or expert endoscopic surveillance are considered if surgery is delayed. [100]

The most important thing for patients is not to ignore alarming symptoms: weight loss, anemia, black stools, early satiety, persistent pain, repeated vomiting, and a family history of diffuse gastric cancer. The earlier an accurate diagnosis is made and treatment is initiated by a specialized team, the greater the chances of controlling the disease. [101]