by Jason Wasserman MD PhD FRCPC
April 19, 2026
Undifferentiated carcinoma of the ovary is a rare and aggressive type of ovarian cancer. It is called “undifferentiated” because the tumor cells have lost nearly all of the features that normally help identify what type of cell they came from. Under the microscope, they look so abnormal and featureless that the pathologist cannot classify them as any specific recognized cancer subtype — unlike, for example, high-grade serous carcinoma or endometrioid carcinoma, which have distinctive appearances. Undifferentiated carcinoma accounts for less than 1% of ovarian carcinomas. In some cases, the tumor contains two components: an undifferentiated area alongside a second area that still resembles a recognizable cancer type, most commonly endometrioid carcinoma. When both components are present, the tumor is called a dedifferentiated carcinoma — a term that reflects the idea that part of the tumor has undergone dedifferentiation, meaning its cells have lost their original identity and become featureless. This article will help you understand the findings in your pathology report — what each term means and why it matters for your care.
What are the symptoms?
Many patients develop symptoms related to a pelvic mass, including abdominal swelling or bloating, pelvic pain, abdominal pressure, or a feeling of fullness. Some patients also experience fatigue or unexplained weight loss. Because undifferentiated carcinoma often grows quickly, it is frequently diagnosed after the cancer has already spread within the abdomen. This means symptoms may be more pronounced at the time of diagnosis than with slower-growing ovarian cancers.
What causes undifferentiated carcinoma of the ovary?
The exact cause is not fully understood. Many cases appear to develop from an existing ovarian cancer — most commonly endometrioid carcinoma — through a process called dedifferentiation, in which tumor cells progressively lose their identifying features and become increasingly abnormal and featureless.
An important mechanism underlying this process involves a group of proteins called the SWI/SNF complex. This complex normally acts as a control system that determines which genes are switched on or off inside a cell — a process called chromatin remodeling, where “chromatin” refers to the tightly packaged DNA inside the cell’s nucleus. When key proteins in this complex stop working — particularly SMARCA4, ARID1A, ARID1B, and SMARCB1 — the cell loses important regulatory control, and it can begin to grow in a disorganized, undifferentiated way. Mutations affecting these SWI/SNF proteins are found in a substantial proportion of undifferentiated and dedifferentiated ovarian carcinomas and are thought to be key drivers of dedifferentiation.
Abnormalities in DNA mismatch repair — the system cells use to fix small copying errors in DNA — are also common, found in approximately one-third of cases.
How is the diagnosis made?
The diagnosis is usually made after the tumor is removed at surgery and examined under the microscope by a pathologist. A biopsy of an abdominal mass may provide the initial diagnosis in some cases. If surgery is performed, the pathologist also examines all other tissues removed at the same time — including the fallopian tubes, uterus, lymph nodes, omentum, and peritoneal biopsies — to determine how far the tumor has spread.
Under the microscope, undifferentiated carcinoma usually forms solid sheets of cells rather than recognizable structures like glands or papillary projections. The cells are often described as discohesive — meaning they do not stick together well and may appear as individual cells or loosely arranged clusters rather than tightly organized groups. They typically have large, irregular nuclei and relatively little surrounding cytoplasm (the material filling the cell body). Some tumors contain cells with rhabdoid features — large cells with abundant pink cytoplasm and an eccentric (off-center) nucleus — or spindle-shaped cells. Areas of necrosis (dead tumor tissue) are common, as is a high mitotic rate — meaning many cells are actively dividing, reflecting rapid growth. Immune cells called tumor-infiltrating lymphocytes are often visible within the tumor.
In dedifferentiated carcinoma, a second recognizable tumor component is present alongside the undifferentiated area — typically a FIGO grade 1 or 2 endometrioid carcinoma that forms gland-like structures. The boundary between the two components is often sharp and abrupt. Identifying this second component is important for the diagnosis and may have implications for treatment planning.
To confirm the diagnosis and rule out other tumors that can appear similar under the microscope — such as high-grade serous carcinoma, neuroendocrine carcinoma, lymphoma, or melanoma — the pathologist uses immunohistochemistry (IHC). This technique uses antibodies to detect specific proteins in the tumor cells. Undifferentiated carcinoma typically shows only limited and patchy staining for epithelial markers such as EMA and cytokeratins (proteins found in most carcinomas), and is usually negative for estrogen receptor (ER), progesterone receptor (PR), and PAX8 (a marker of Müllerian origin). Most tumors show a normal (wild-type) p53 staining pattern, which helps distinguish them from high-grade serous carcinoma, where abnormal p53 staining is almost universal. Loss of SWI/SNF proteins — particularly SMARCA4, ARID1A, or ARID1B — detected by IHC supports the diagnosis and reflects the underlying genetic changes described above.
Once the diagnosis is confirmed, imaging — typically CT of the chest, abdomen, and pelvis — is performed to determine the full extent of disease and guide staging and treatment planning.
Histologic grade
Undifferentiated carcinoma of the ovary is considered high grade by definition. The grading systems used for other ovarian carcinomas — such as the FIGO grades 1, 2, or 3 for endometrioid carcinoma — do not apply here. The absence of any recognizable differentiation is itself the defining feature of this tumor type and places it among the most aggressive ovarian cancers. If a dedifferentiated carcinoma is present, the pathology report may describe the grade of the differentiated (recognizable) component, but the undifferentiated component is the dominant factor driving clinical behavior and treatment decisions.
Tumor spread
Undifferentiated carcinoma is often diagnosed at an advanced stage because it tends to grow quickly. Tumor cells may spread to the peritoneum (the thin lining of the abdominal cavity), omentum, lymph nodes, fallopian tubes, uterus, and other abdominal or pelvic structures. The presence of tumor cells outside the ovary is the most important factor affecting prognosis and stage.
Ovarian capsule status
The outer covering of the ovary is called the capsule. The pathologist will note whether the capsule is intact or ruptured, and whether tumor is present on the outer surface. These findings affect the stage:
- Intact capsule, no surface tumor — Suggests the cancer is still contained within the ovary, associated with an earlier stage.
- Ruptured capsule or tumor on the surface — Even when no other spread is found, capsule rupture or surface involvement increases the stage.
- Intraoperative rupture — If the capsule ruptures during surgery rather than before, this is noted separately and also affects staging.
Lymphovascular invasion
Lymphovascular invasion means that tumor cells have been found inside small blood vessels or lymphatic channels within the tissue. This finding indicates that tumor cells may have had an opportunity to travel to lymph nodes or distant sites, and it can influence staging and treatment planning.
Lymph nodes
Lymph nodes are small, bean-shaped structures that help filter the body’s lymphatic fluid and support the immune system. In ovarian cancer surgery, lymph nodes from the pelvis and along the major abdominal blood vessels (para-aortic nodes) may be removed and examined. If tumor cells are found in the lymph nodes, the cancer is considered to have spread beyond the ovary, and the stage increases.
The pathology report will describe:
- The total number of lymph nodes examined
- The number of lymph nodes containing tumor cells
- The size of the largest tumor deposit
- The location of any involved nodes (pelvic vs. para-aortic)
Lymph node deposits are classified by size. Isolated tumor cells (measuring 0.2 mm or less) are recorded as pN0(i+) and are not counted as definitive metastases in all staging systems. Deposits between 0.2 mm and 10 mm are classified as pN1a (small metastases), and deposits larger than 10 mm are classified as pN1b (large metastases). These size distinctions affect the N stage.
Biomarker and molecular testing
Biomarker testing examines specific proteins and genetic changes in tumor cells that may help guide treatment decisions and identify inherited cancer risk. The most clinically important biomarkers in undifferentiated carcinoma of the ovary are the mismatch repair proteins and the SWI/SNF complex proteins.
Mismatch repair proteins (MMR)
Mismatch repair proteins — MLH1, PMS2, MSH2, and MSH6 — work together to fix small copying errors that arise when cells divide and duplicate their DNA. When one or more of these proteins is absent or not working, errors accumulate throughout the genome, and the tumor is described as mismatch repair–deficient (dMMR) or, equivalently, microsatellite instability–high (MSI-H). This is found in approximately one-third of undifferentiated ovarian carcinomas, making it one of the highest rates of any ovarian cancer subtype.
When MMR deficiency is present, it has two important implications. First, dMMR/MSI-H tumors may be eligible for immunotherapy with pembrolizumab (Keytruda) — a drug that helps the immune system recognize and attack cancer cells. Pembrolizumab is approved for use in any solid tumor that is dMMR/MSI-H and has progressed after prior treatment, regardless of where in the body the cancer started. Second, MMR deficiency may indicate Lynch syndrome — an inherited condition caused by a mutation in one of the MMR genes that runs in families and significantly raises the lifetime risk of ovarian, uterine, colorectal, and several other cancers. This means a positive MMR deficiency result may have implications not only for the patient’s own treatment but also for their blood relatives, who may be at elevated cancer risk without knowing it.
Testing is performed by immunohistochemistry on tumor tissue. Results are reported as retained expression (normal) or loss of expression (abnormal) for each of the four proteins. When MLH1 and PMS2 are both lost, additional testing for a BRAF V600E mutation or for MLH1 promoter methylation (a chemical modification that silences the gene) is typically performed to determine whether the loss is sporadic — meaning it arose randomly in the tumor — or whether it points to Lynch syndrome. Loss of MSH2 or MSH6, or unexplained MLH1/PMS2 loss, should prompt referral to a genetic counsellor for Lynch syndrome assessment.
SWI/SNF complex proteins (SMARCA4, ARID1A, ARID1B, SMARCB1)
The SWI/SNF complex is a group of proteins that acts as a master control system inside cells, determining which genes are switched on or off. It does this by repositioning the tightly coiled DNA inside the nucleus, making certain genes accessible or inaccessible to the cell’s reading machinery — a process called chromatin remodeling. When key proteins in this complex are lost due to genetic mutations, the cell’s gene regulation breaks down, and it can lose its normal identity and begin growing in an uncontrolled, undifferentiated way.
The most commonly lost SWI/SNF proteins in undifferentiated ovarian carcinoma are SMARCA4 (also called BRG1), ARID1A, and ARID1B. Loss of these proteins is assessed by immunohistochemistry on tumor tissue, and results are reported as retained expression (normal) or loss of expression (abnormal). When loss is identified, it supports the diagnosis and provides important information about the tumor’s underlying biology. Research into therapies that specifically target SWI/SNF-deficient tumors is ongoing, and clinical trials may be relevant for patients with these findings.
For more information about biomarker testing, see the Biomarkers and Molecular Testing section.
Pathologic stage (pTNM)
Staging describes how far the cancer has spread. Undifferentiated carcinoma of the ovary is staged using the AJCC TNM system, which closely corresponds to the FIGO staging system used by gynecologic oncologists. The stage is made up of three components: T (how far the tumor has grown locally), N (whether it has spread to lymph nodes), and M (whether it has spread to distant organs). M stage is determined by imaging and is not typically assigned in the pathology report unless distant spread was sampled at surgery.
Tumor stage (pT)
- pT1 (FIGO Stage I) — Tumor is limited to one or both ovaries or fallopian tubes.
- pT1a — Tumor in one ovary or fallopian tube only; capsule intact; no tumor cells in abdominal fluid.
- pT1b — Tumor involves both ovaries or fallopian tubes; capsules intact; no tumor cells in abdominal fluid.
- pT1c — Tumor limited to ovary/fallopian tube but with capsule rupture, tumor on the outer surface, or cancer cells in abdominal fluid or washings.
- pT2 (FIGO Stage II) — Tumor has spread beyond the ovaries or fallopian tubes into the pelvis.
- pT2a — Spread to the uterus, the other fallopian tube, or the other ovary.
- pT2b — Spread to other pelvic tissues such as the bladder or rectum.
- pT3 (FIGO Stage III) — Tumor has spread beyond the pelvis to the peritoneum or regional lymph nodes.
- pT3a — Microscopic spread to the peritoneum outside the pelvis, with or without regional lymph node involvement.
- pT3b — Visible tumor deposits up to 2 cm on the peritoneum outside the pelvis, with or without lymph node involvement.
- pT3c — Visible tumor deposits larger than 2 cm outside the pelvis, or spread to the outer surface (capsule) of the liver or spleen, with or without lymph node involvement.
Note: Spread inside the substance of the liver or spleen (rather than only on their surface) is classified as M1 (Stage IVB).
Nodal stage (pN)
- pN0 — No cancer cells found in regional lymph nodes.
- pN0(i+) — Only isolated tumor cells (0.2 mm or less) found in lymph nodes; not counted as definitive metastases in all staging systems.
- pN1 — Cancer cells present in regional lymph nodes.
- pN1a — Tumor deposits up to 10 mm.
- pN1b — Tumor deposits larger than 10 mm.
What is the prognosis?
The prognosis for undifferentiated carcinoma of the ovary is generally poor, reflecting both its aggressive behavior and the fact that most cases are diagnosed at an advanced stage. The tumor grows quickly and tends to spread rapidly within the abdomen. Median overall survival in published series is often less than one year for advanced-stage disease, though outcomes vary and some patients — particularly those with early-stage disease or dMMR/MSI-H tumors eligible for immunotherapy — may have better outcomes.
Factors associated with outcomes include:
- Stage — Stage at diagnosis is the most important prognostic factor. The minority of patients diagnosed at stage I have substantially better outcomes than those with advanced disease.
- MMR status — Tumors with mismatch repair deficiency (dMMR/MSI-H) may respond to immunotherapy with pembrolizumab, which represents an important treatment opportunity in this otherwise difficult-to-treat cancer.
- Residual disease after surgery — Complete removal of all visible tumor is associated with better outcomes where achievable.
- Dedifferentiated vs. purely undifferentiated — The distinction between dedifferentiated carcinoma (with a recognizable low-grade component) and purely undifferentiated carcinoma may influence treatment approach, though both are considered aggressive.
- SWI/SNF protein loss — The clinical significance of specific SWI/SNF protein losses is an active area of research, with potential implications for emerging targeted therapies.
What happens after the diagnosis?
Treatment is planned by a multidisciplinary team that typically includes a gynecologic oncologist, medical oncologist, pathologist, and radiologist.
Surgery is the cornerstone of treatment and aims to remove as much tumor as possible (cytoreductive surgery). Standard surgery involves the removal of both ovaries, both fallopian tubes, the uterus, and the omentum, along with the resection of any visible peritoneal deposits. Achieving no residual disease is the goal, though the rapid growth pattern of this tumor means that complete cytoreduction is not always possible.
Chemotherapy is recommended for most patients after surgery. Because undifferentiated carcinoma is rare and poorly characterized in clinical trials, there is no dedicated evidence base for a single optimal regimen. In practice, platinum-based chemotherapy — most commonly carboplatin and paclitaxel — is used as first-line treatment, as for other high-grade ovarian carcinomas. However, responses to standard chemotherapy are often limited, particularly in SWI/SNF-deficient tumors, which can be resistant to conventional treatment.
For patients with dMMR/MSI-H tumors, immunotherapy with pembrolizumab is an important option in recurrent or advanced disease. Patients should be assessed for Lynch syndrome if MMR deficiency is identified, and referral to a genetic counsellor is recommended. Clinical trial participation is strongly encouraged given the rarity of this tumor and the limited evidence base for standard treatments.
Follow-up after treatment involves regular clinical assessments and imaging, with the schedule determined by the stage and treatment received.
Questions to ask your doctor
- Is my tumor purely an undifferentiated carcinoma, or does it also have a differentiated component that makes it a dedifferentiated carcinoma?
- What stage is my ovarian cancer, and how far has it spread?
- Was mismatch repair testing performed, and were any of the MMR proteins lost?
- If MMR deficiency was found, do I need testing for Lynch syndrome, and should my family members be referred for testing?
- Were SWI/SNF protein tests performed (SMARCA4, ARID1A, ARID1B), and what were the results?
- Am I eligible for pembrolizumab-based immunotherapy based on my MMR results?
- What chemotherapy regimen do you recommend, and what response rates are expected for this tumor type?
- Was the tumor completely removed at surgery, and if not, what are the next steps?
- Is there a clinical trial that might be appropriate for my situation?
- What follow-up schedule do you recommend, and what signs of recurrence should I watch for?
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