Signet Ring Cell Carcinoma of the Stomach: Understanding Your Pathology Report

by Jason Wasserman MD PhD FRCPC
July 31, 2026

Signet ring cell carcinoma of the stomach is a type of stomach cancer in which the cancer cells lose their attachments to one another and spread individually through the stomach wall instead of forming glands. Each cell fills with a large droplet of mucus that pushes the nucleus, the compartment holding the cell’s genetic material, to one edge. Under the microscope, this produces the appearance of a ring with a stone set in it, which is where the name comes from.

It is a form of adenocarcinoma of the stomach, not a separate cancer, and it accounts for a substantial minority of stomach cancers. It behaves differently enough from the gland-forming types that it is worth understanding on its own terms: it is harder to see and to sample, it spreads through the stomach wall in a different pattern, and it is more often linked to an inherited condition.

One point matters before anything else. Signet ring cell carcinoma is diagnosed when signet ring cells make up more than half of the tumor. A report describing an adenocarcinoma with a signet ring cell component, or with signet ring cell features, is describing a different and generally less concerning situation, in which some signet ring cells are present within a tumor that is mostly gland-forming. If you are unsure which your report describes, it is worth asking directly.

This article will help you understand the findings in your pathology report, what each term means, and why it matters for your care.

What causes signet ring cell carcinoma of the stomach?

The causes of signet ring cell carcinoma of the stomach differ from those of the more common gland-forming types. Gland-forming stomach cancers usually arise from a long sequence of damage driven by Helicobacter pylori infection, in which the lining thins, is replaced by intestinal-type cells, becomes dysplastic, and finally becomes cancer. Signet ring cell carcinoma does not follow that path, and it often arises in a stomach lining that otherwise looks healthy.

What is known about its causes includes:

Loss of E-cadherin — E-cadherin is the protein that holds neighboring cells together. Almost all signet ring cell carcinomas have lost it, which is the direct explanation for why the cells scatter rather than forming a mass. This loss can occur in the tumor alone, or it can be inherited.
Inherited gene changes — A minority of cases are caused by an inherited change in the CDH1 gene, which makes E-cadherin. This causes hereditary diffuse gastric cancer, described in its own section below. Changes in a related gene, CTNNA1, account for a smaller number of families.
Younger age and female sex — This type occurs at a younger average age than gland-forming stomach cancer and is more common in women, reversing the male predominance seen in other stomach cancers.
Rising frequency — While stomach cancer overall has become less common in Western countries as H. pylori infection has declined, signet ring cell carcinoma has become relatively more common, particularly in younger people. The reason is not understood.

Diet, smoking, and H. pylori play a smaller role here than in gland-forming stomach cancer. This is worth stating plainly, because people often assume something they ate or did brought this on. For most people with this diagnosis, no identifiable cause is ever found.

What are the symptoms of signet ring cell carcinoma of the stomach?

Signet ring cell carcinoma of the stomach frequently causes no symptoms until it is advanced, and the symptoms it does cause are different from those of gland-forming stomach cancers.

Because the cancer cells spread through the wall as scattered individual cells rather than forming a lump that breaks down and bleeds, obvious bleeding is less common than with other stomach cancers. Instead, the wall gradually thickens and stiffens, so the stomach loses its ability to stretch. The result is feeling full after only a few mouthfuls, persistent bloating, nausea, and steady weight loss. Vague upper abdominal discomfort is common. When a large part of the stomach is affected the whole organ can become rigid, an appearance historically described as linitis plastica, meaning a leather-bottle stomach.

Because the tumor can reach the outer surface of the stomach early, some people first develop symptoms from spread into the abdominal cavity: swelling of the abdomen from fluid, called ascites, or a mass in an ovary. Feeling full quickly and losing weight without an obvious explanation are the symptoms most worth taking seriously, and they are easily mistaken for indigestion for months before the diagnosis is made.

How is the diagnosis made?

Signet ring cell carcinoma of the stomach is diagnosed only after tissue from the stomach is examined under a microscope by a pathologist. Tissue is obtained during an upper endoscopy, in which a thin flexible tube with a camera is passed through the mouth so the lining can be inspected and small samples called biopsies taken.

This is the hardest type of stomach cancer to diagnose, and it is worth understanding why. Because the cells scatter beneath the surface rather than growing outward, the lining above them can look entirely normal, or show only a subtle pale or slightly sunken patch. There may be no mass to aim at. Biopsies taken from a normal-looking area can miss the tumor entirely, and it is not unusual for a person to have one or more negative biopsies before the diagnosis is made. If your endoscopy was repeated, or if you were told deeper or more numerous biopsies were needed, this is why. When the stomach wall looks thickened on a CT scan, or feels stiff and does not expand normally during endoscopy, those findings can be more telling than the appearance of the lining itself.

Under the microscope, the pathologist looks for individual cancer cells and small clusters infiltrating between the normal glands and through the wall, often accompanied by desmoplasia, a dense scar-like reaction of the surrounding tissue that accounts for the stiffening. The classic signet ring cell has a clear mucus-filled body and a crescent-shaped nucleus flattened against one side.

Several other things can look like signet ring cells, and distinguishing them matters a great deal. Histiocytes, a type of immune cell that accumulates in inflamed tissue, can closely mimic them, as can a harmless change called signet ring cell change in which normal surface cells become distended with mucus. To resolve these, the pathologist may use immunohistochemistry, a test using antibodies to detect specific proteins. Pancytokeratin stains the scattered tumor cells and makes them stand out against the background, and it is often used simply to count how much tumor is present. E-cadherin staining is typically lost or abnormal in the tumor cells. Special stains such as mucicarmine or PAS-D confirm that the droplet inside the cell is mucin.

Once cancer is confirmed, imaging determines how far it has spread, usually with CT scans of the chest, abdomen, and pelvis. A laparoscopy, a small operation to look inside the abdomen directly with a camera, is performed before planning surgery in most cases of this type, because deposits on the surface of the abdominal lining are common and are frequently too small to appear on a scan.

Names used for this diagnosis

Signet ring cell carcinoma of the stomach is described using several different terms, and reports from different laboratories or different years may not use the same one. All of the following describe the same tumor or closely overlapping categories:

Poorly cohesive carcinoma, signet ring cell type — The current World Health Organization term and the most precise one. “Poorly cohesive” describes cells that do not stick together; “signet ring cell type” specifies that more than half of them have the signet ring appearance.
Signet ring cell carcinoma — The older and still widely used name for the same tumor. Reports and patients both continue to use it.
Poorly cohesive carcinoma, not otherwise specified — Cells do not stick together, but fewer than half have the signet ring appearance. This sits in the same family and is managed the same way.
Diffuse type adenocarcinoma — A term from the older Laurén classification. Signet ring cell carcinoma falls within this category, which also includes other poorly cohesive tumors.
Linitis plastica — Not a diagnosis but a description of a stomach whose wall has become thickened and rigid over a wide area. It is usually caused by this type of cancer.

If your report uses one term and your doctor uses another, they are almost certainly describing the same thing. What matters more than the label is the proportion of signet ring cells, the depth of invasion, and the lymph node result.

Tumor grade

Grade normally describes how closely cancer cells resemble the normal cells they came from, based on how much of the tumor still forms glands. Signet ring cell carcinoma of the stomach forms no glands at all, so it is classified as poorly differentiated, or grade 3, by definition.

This is worth understanding because “poorly differentiated” and “high grade” sound alarming and are often the words people notice first. For this tumor type, the grade is a direct consequence of what the cells look like rather than an independent measurement of how the cancer will behave. It adds essentially no information beyond the diagnosis itself. The findings that genuinely predict behavior are the depth of invasion, the number of involved lymph nodes, and whether the cancer has reached the abdominal lining.

Depth of invasion

Depth of invasion describes how far a signet ring cell carcinoma has grown through the wall of the stomach, and it is the single most important finding on the report. The stomach wall is built in layers: the mucosa or innermost lining, where the cancer begins; the submucosa beneath it, carrying blood vessels and lymphatic channels; the muscularis propria, the thick muscle layer; the subserosa; and the serosa, the smooth outer covering facing the abdominal cavity.

Two features of this tumor type make depth particularly important. First, tumors confined to the mucosa or submucosa are described as early gastric cancer, and at that stage this type carries an excellent outlook, better than gland-forming cancers of the same stage. Second, once the tumor breaks through the serosa, cancer cells can shed directly into the abdominal cavity and settle on the surfaces of other organs. Because these cells travel individually and are small in number, this spread happens earlier and more readily than with gland-forming stomach cancers, and it is the pattern of spread that most often determines the outcome.

The deepest layer the tumor reaches determines the pathologic tumor stage (pT), described further below.

Lymphovascular invasion

Lymphovascular invasion means that cancer cells from the signet ring cell carcinoma were seen inside a small blood vessel or lymphatic channel. It is reported as present or absent, and it indicates that cells have found a route to travel to lymph nodes or to distant organs.

In a tumor confined to the mucosa being considered for removal through the endoscope, finding lymphovascular invasion usually shifts the discussion toward surgery instead, because it signals that cancer may already have reached the lymph nodes that endoscopic treatment leaves behind.

Perineural invasion

Perineural invasion means that cancer cells were seen surrounding or growing into a nerve, which they can use as a pathway to extend beyond the main tumor. Your report will state whether it is present or absent.

Perineural invasion is found more often in signet ring cell carcinoma than in gland-forming stomach cancers, reflecting the same tendency of these cells to infiltrate widely rather than form a discrete mass. It is associated with a higher risk that cancer will return near the original site.

Surgical margins

A margin is the cut edge of the tissue removed during surgery. The pathologist inks these edges and examines them under the microscope to determine whether cancer cells reach the cut surface. For a stomach specimen, the proximal margin (toward the esophagus), the distal margin (toward the small intestine), the radial or outer soft tissue margin, and the omental margin are each reported separately.

Negative margin — No cancer cells reach the inked edge. The report usually also gives the distance in millimeters to the closest margin.
Positive margin — Cancer cells are present at the inked edge, meaning cancer may remain in the body.

Margins deserve particular attention in this tumor type. Because the cells travel individually and invisibly, the true extent of the cancer often reaches well beyond what the surgeon can see or feel, and positive margins are more common than with gland-forming tumors. Surgeons therefore aim to remove a wider cuff of normal-looking stomach, and it is common for the cut ends to be checked by frozen section during the operation itself, so that more tissue can be taken immediately if cancer cells are found. If your operation took longer than expected, or if you were told tissue was checked while you were still in the operating room, this is usually the reason.

Lymph nodes

Lymph nodes are small immune organs found around the stomach and along the blood vessels supplying it. Cancer cells that enter lymphatic channels can become trapped in them, and cancer found in a lymph node is a form of metastasis. During surgery the nearby nodes are removed so the pathologist can examine them.

Your report will state how many nodes were examined and how many contained cancer. Guidelines recommend that at least 16 be assessed for accurate staging. In signet ring cell carcinoma, deposits within a node are sometimes made up of only a few scattered cells rather than an obvious mass, so the pathologist may use a cytokeratin stain to find them.

The number of involved nodes determines the nodal stage (pN) and is among the strongest predictors of outcome. Worth noting is that at the earliest stage, when the tumor is still confined to the mucosa, this type spreads to lymph nodes less often than gland-forming cancers do. It is at more advanced depths that the pattern reverses.

Peritoneal spread and washing cytology

The peritoneum is the smooth lining covering the inside of the abdominal cavity and the surface of the organs within it. Signet ring cell carcinoma reaches this lining more readily than other stomach cancers, because single cells that break through the outer surface of the stomach can float free in the small amount of fluid that normally circulates in the abdomen and settle elsewhere.

For this reason, a sample of that fluid is usually collected and examined during laparoscopy or surgery. Sterile fluid is introduced into the abdomen, collected again, and examined under the microscope for cancer cells. This is called peritoneal washing cytology, and the result appears on your report:

Negative cytology — No cancer cells were found in the fluid. This is the more favorable result and does not change the stage.
Positive cytology — Cancer cells were found. Even when no visible deposits are present anywhere, this result classifies the cancer as stage IV, because free cancer cells in the abdomen behave as if they have spread to a distant site.

A positive result can be difficult to absorb when scans looked clear, and the person feels well, so it is worth understanding what it means practically. It generally shifts treatment toward drug therapy rather than immediate surgery, and it does not mean treatment has no purpose. Some people whose cytology becomes negative after chemotherapy go on to have surgery.

Spread to the peritoneum can also produce deposits on the ovaries, which are called Krukenberg tumors. If a woman is found to have masses in both ovaries made up of signet ring cells, the stomach is the most common place the cancer started, and a search for a gastric primary follows.

Treatment effect

When chemotherapy is given before surgery, the pathologist assesses how much living cancer remains in the removed stomach and assigns a treatment response score, most often using the modified Ryan scheme, from score 0 (no living cancer cells remain) through score 3 (extensive cancer remains with no evidence of response). When a specimen is removed after chemotherapy, the stage is written with a “y” in front, as ypT and ypN.

Signet ring cell carcinoma responds less well to chemotherapy than gland-forming stomach cancers, and complete responses are less common. The higher the proportion of signet ring cells, the less responsive the tumor tends to be. This is a recognized limitation rather than a treatment failure, and it is one reason surgery is sometimes prioritized and why clinical trials are particularly worth asking about in this tumor type.

Biomarker and molecular testing

Biomarkers are proteins or genetic changes measured in tumor tissue that predict whether a signet ring cell carcinoma is likely to respond to a particular drug. Testing is performed when the cancer is advanced, recurrent, or has spread. The pattern of results in this tumor type differs from gland-forming stomach cancers in ways worth knowing.

HER2 — Positive far less often in signet ring cell carcinoma than in gland-forming stomach cancers, in the range of one in ten rather than one in four. Testing is still performed, since a positive result opens HER2-targeted treatment, but a negative result is the expected finding here.
Claudin 18.2 — This is the most useful biomarker in this tumor type. Claudin 18.2 is a protein sealing the junctions between stomach lining cells, and poorly cohesive and signet ring cell tumors express it more often than gland-forming tumors do, including in disease that has spread to the peritoneum. A tumor is positive when at least 75% of cancer cells show moderate to strong staining around their outer edge, which indicates eligibility for zolbetuximab, an antibody given with chemotherapy for advanced HER2-negative disease.
PD-L1 — Reported as a Combined Positive Score (CPS). Levels tend to be lower in this tumor type than in others. A CPS of 1 or higher is the minimum threshold for checkpoint inhibitor eligibility, with higher scores predicting greater benefit.
Mismatch repair (MMR) — Deficiency is less common in signet ring cell carcinoma than in other stomach cancers. When it is found, it indicates eligibility for immunotherapy regardless of where the cancer started, and it raises the possibility of Lynch syndrome, an inherited condition affecting blood relatives.

The overall picture is that the biomarkers most useful in gland-forming stomach cancer are less often positive here, while claudin 18.2 is more often positive. A report showing HER2 negative, PD-L1 low, and mismatch repair proficient is the expected result for this tumor type and is not a sign that testing was inadequate. You can read more in our Biomarkers and Genetic Testing section.

CDH1 and hereditary diffuse gastric cancer

Most signet ring cell carcinomas of the stomach are not inherited. In a minority, however, the cancer is caused by an inherited change in the CDH1 gene, the gene that makes E-cadherin. This condition is called hereditary diffuse gastric cancer, and identifying it matters because the implications extend to blood relatives.

Genetic testing is generally offered when signet ring cell or diffuse gastric cancer occurs before about age 50, when more than one family member has had diffuse gastric cancer, or when diffuse gastric cancer occurs in a family that also has lobular breast cancer. Only diffuse-type stomach cancer and lobular-type breast cancer count toward these criteria; gland-forming stomach cancers and other types of breast cancer do not.

For someone found to carry a CDH1 change, the main considerations are:

Lifetime risk of stomach cancer — Currently estimated in the range of 10% to 42%. Older figures were considerably higher; as testing has become more widespread and families without dramatic cancer histories have been identified, the estimates have fallen substantially.
Preventive removal of the stomach — Removing the entire stomach before cancer develops eliminates that risk, and it has been the standard recommendation, usually in early adulthood. It is a major operation with permanent effects on eating and nutrition, and most people have some digestive symptoms a year afterward.
Endoscopic surveillance as an alternative — Regular endoscopy with multiple biopsies at a center experienced in this condition is now considered a reasonable option for people who wish to postpone or decline surgery. Guidance has shifted toward shared decision-making between surgery and surveillance rather than a single recommendation. Surveillance is imperfect because early cancer foci usually sit beneath normal-looking lining, but recent long-term studies suggest progression to advanced cancer while under active surveillance is uncommon.
Breast cancer risk in women — CDH1 also raises the risk of lobular breast cancer. Annual breast MRI from around age 30 is generally recommended, and preventive mastectomy is considered on an individual basis.
Testing for relatives — The gene change is passed on in an autosomal dominant pattern, meaning each child of a carrier has a 50% chance of inheriting it. Testing is offered to first-degree relatives through a genetics service.

A related gene, CTNNA1, accounts for a small number of families. Because less is known about it, carriers are generally offered surveillance rather than preventive surgery. Some families meet the clinical criteria but have no identifiable gene change; they are managed with surveillance and are described as having a hereditary diffuse gastric cancer-like syndrome.

Pathologic stage (pTNM)

Pathologic stage describes how far a signet ring cell carcinoma of the stomach has grown and whether it has spread. It uses the TNM system of the American Joint Committee on Cancer (AJCC), 8th edition. The letter p means the stage was determined by examining tissue under the microscope. If chemotherapy was given before surgery, the stage is written as ypT and ypN.

Tumor stage (pT)

pT1a — The tumor is confined to the mucosa.
pT1b — The tumor has grown into the submucosa.
pT2 — The tumor has grown into the muscularis propria, the main muscle layer.
pT3 — The tumor has grown through the muscle layer into the subserosal connective tissue without breaking through the outer surface.
pT4a — The tumor has broken through the serosa, the outer surface of the stomach.
pT4b — The tumor has grown directly into a neighboring organ or structure.

Nodal stage (pN)

pN0 — No cancer was found in any lymph nodes examined.
pN1 — Cancer was found in one or two lymph nodes.
pN2 — Cancer was found in three to six lymph nodes.
pN3a — Cancer was found in seven to fifteen lymph nodes.
pN3b — Cancer was found in sixteen or more lymph nodes.
pNX — Lymph nodes were not submitted or could not be assessed.

A positive peritoneal washing cytology result places the cancer at stage IV regardless of the pT and pN results.

What is the prognosis for signet ring cell carcinoma of the stomach?

The prognosis for signet ring cell carcinoma of the stomach depends on stage more sharply than for other stomach cancers, and the direction of its effect actually reverses across the stages. This is unusual and it is frequently misreported, so it is worth setting out clearly.

At an early stage, when the tumor is still confined to the mucosa or submucosa, signet ring cell carcinoma does better than other stomach cancers of the same stage. It spreads to lymph nodes less often at this depth, and five-year survival in large studies has been around 90%, higher than for gland-forming cancers at the same stage. If your report describes a pT1 tumor with negative lymph nodes, the widely repeated statement that this is a particularly dangerous type of stomach cancer does not apply to your situation.

At an advanced stage, when the tumor has grown through the muscle layer or reached multiple lymph nodes, the picture reverses and outcomes are less favorable than for gland-forming cancers of the same stage. The reasons are the tendency to spread to the peritoneum, the difficulty of achieving clear margins, and the reduced response to chemotherapy.

Much of the reputation this diagnosis carries comes from the fact that it is more often found late, because it causes few symptoms and is hard to see. Stage for stage, the picture is more nuanced than the reputation suggests.

Findings on your report associated with poorer outcomes include deeper invasion through the stomach wall, a greater number of involved lymph nodes, a positive surgical margin, positive peritoneal washing cytology, lymphovascular or perineural invasion, and a poor response to chemotherapy given before surgery.

What happens after this diagnosis?

After signet ring cell carcinoma of the stomach is confirmed, the pathology report is reviewed alongside imaging by a multidisciplinary team including surgery, medical oncology, radiology, pathology, genetics, and dietetics.

For a small tumor confined to the mucosa, endoscopic removal is possible in carefully selected cases, though the criteria are stricter than for gland-forming cancers because of the risk that scattered cells extend beyond what can be seen. Most people with tumors at this depth are offered surgery instead.

For tumors that have grown deeper or reached lymph nodes without spreading to distant sites, treatment usually combines chemotherapy with surgery, most often perioperative chemotherapy given before and after the operation. Surgery removes part or all of the stomach along with the regional lymph nodes, with wider margins than for other types and frozen section checks during the operation. Because this type responds less well to chemotherapy, the balance between chemotherapy and proceeding directly to surgery is sometimes weighed differently, and this is a reasonable thing to ask about.

For cancer that has spread, treatment is directed by the biomarker results, with claudin 18.2-positive disease opening the option of zolbetuximab alongside chemotherapy. Where disease is confined to the peritoneum, some centers offer treatments directed into the abdominal cavity, generally within clinical trials.

Genetic counseling is offered to most people with this diagnosis, particularly those under 50 or with a family history. Nutrition is central to recovery after stomach surgery: smaller frequent meals become necessary, and iron, calcium, vitamin D, and vitamin B12 can all become deficient, with vitamin B12 requiring lifelong injections after complete removal of the stomach. A dietitian is generally involved from the outset.

Questions to ask your doctor

What proportion of my tumor was made up of signet ring cells?
Is my diagnosis signet ring cell carcinoma, or an adenocarcinoma with some signet ring cells?
How deeply did the tumor grow into the wall of my stomach?
How many lymph nodes were examined, and how many contained cancer?
Were all of the surgical margins negative, and were they checked during the operation?
Was peritoneal washing cytology performed, and what did it show?
Was a laparoscopy done to look for spread inside the abdomen?
Given my stage, how does my outlook compare with other types of stomach cancer?
What were my HER2, claudin 18.2, PD-L1, and mismatch repair results?
Am I eligible for zolbetuximab or another targeted treatment?
Should I have genetic testing for CDH1, and what would a positive result mean for my family?
How well is this type of cancer expected to respond to chemotherapy in my case?
Are there clinical trials open to someone with my stage and tumor type?
What changes to my eating should I expect, and will I need vitamin or mineral supplements?
What follow-up tests and imaging will I need, and how often?