Undifferentiated carcinoma of the ovary is a rare and aggressive type of ovarian cancer. It is called “undifferentiated” because the tumour cells do not resemble any specific normal tissue when examined under the microscope.
In some cases, the tumour contains two components. One component is an undifferentiated carcinoma, and the other component shows features of another ovarian cancer, most commonly endometrioid carcinoma. When both components are present, the tumour is called dedifferentiated carcinoma.
Undifferentiated carcinoma is uncommon and represents less than 1% of ovarian carcinomas.
What are the symptoms of undifferentiated carcinoma of the ovary?
Many patients with undifferentiated carcinoma of the ovary develop symptoms related to a pelvic mass. Symptoms may include abdominal swelling or bloating, pelvic pain, abdominal pressure, or a feeling of fullness. Some patients may also experience fatigue or unexplained weight loss.
Because these tumours often grow quickly, they are frequently diagnosed after the cancer has already spread within the abdomen.
What causes undifferentiated carcinoma of the ovary?
The exact cause of undifferentiated carcinoma of the ovary is not fully understood. Some tumours appear to develop from another ovarian cancer, most commonly endometrioid carcinoma, through a process called dedifferentiation. In this process, tumour cells lose the features that normally help identify the type of tumour they came from.
Genetic changes affecting proteins that regulate how DNA is packaged and expressed within cells appear to play an important role. These include alterations in genes such as ARID1A, ARID1B, and SMARCA4. Abnormalities in DNA repair pathways are also common.
How is this diagnosis made?
The diagnosis of undifferentiated carcinoma of the ovary usually begins when a mass in the ovary is detected during imaging or surgery.
The tumour is removed and examined under the microscope by a pathologist. The pathologist studies the appearance of the tumour cells and their growth pattern to determine the type of ovarian cancer.
If surgery is performed, the pathologist also examines other tissues removed during the operation, including the fallopian tubes, uterus, lymph nodes, and abdominal tissues. This examination helps determine how far the tumour has spread and is important for staging.
Microscopic features
Under the microscope, undifferentiated carcinoma usually forms solid sheets of tumour cells rather than glands or papillary structures.
The tumour cells often appear discohesive, meaning they do not stick together well and may grow as single cells, clusters, or sheets. The cells are often round with very little cytoplasm, although some tumours contain cells with rhabdoid or spindle-shaped features.
Areas of extensive necrosis are common, and the tumour typically shows high mitotic activity, meaning that many cells are actively dividing. Immune cells called tumour-infiltrating lymphocytes are often present within the tumour.
In dedifferentiated carcinoma, a second tumour component is present. This component usually resembles endometrioid carcinoma and forms gland-like structures. The boundary between the differentiated and undifferentiated components may be abrupt.
Immunohistochemistry
Immunohistochemistry is a laboratory test that uses antibodies to detect specific proteins inside tumour cells. These tests help confirm the diagnosis and distinguish undifferentiated carcinoma from other tumours that can appear similar under the microscope.
Undifferentiated carcinoma usually shows limited staining for epithelial markers, such as EMA or cytokeratins. This staining may be focal rather than diffuse.
Most tumours are negative for estrogen receptor (ER) and progesterone receptor (PR). PAX8 may be negative or only focally positive.
Loss of proteins involved in chromatin remodeling, such as SMARCA4 (BRG1) or ARID1A, may also be detected. These findings help distinguish undifferentiated carcinoma from other tumours such as high-grade serous carcinoma or neuroendocrine carcinoma.
Biomarkers
Biomarker testing examines proteins or genetic changes in tumour cells that may help guide treatment decisions. Some tests use immunohistochemistry to detect proteins in tumour cells, while others evaluate changes in tumour DNA.
Mismatch repair proteins (MMR)
Mismatch repair proteins help repair errors that arise during DNA replication. The most commonly tested proteins are MLH1, PMS2, MSH2, and MSH6.
Testing is performed using immunohistochemistry. Results are reported as retained expression (normal) or loss of expression (abnormal).
Mismatch repair deficiency is found in about one-third of undifferentiated ovarian carcinomas. If a mismatch repair deficiency is identified, this may suggest Lynch syndrome and may indicate that the tumour could respond to immunotherapy.
SWI/SNF complex proteins
Proteins involved in the SWI/SNF chromatin remodeling complex, such as SMARCA4, SMARCA2, SMARCB1, and ARID1A, help regulate how DNA is packaged and used by cells.
Loss of these proteins is common in undifferentiated and dedifferentiated carcinomas. Testing is usually performed using immunohistochemistry, and results are reported as retained or lost expression.
Loss of these proteins can support the diagnosis and may help explain how the tumour developed.
p53
p53 is a protein that helps regulate cell growth and repair damaged DNA.
Results are usually reported using immunohistochemistry as wild-type (normal pattern) or abnormal (mutant-type pattern). Most undifferentiated ovarian carcinomas show a wild-type p53 pattern, which helps distinguish them from high-grade serous carcinoma.
Other features to look for in your pathology report
Tumor spread
Pathologists examine the tumour to determine whether it has spread beyond the ovary.
Undifferentiated carcinoma is often diagnosed at an advanced stage, and tumour cells may involve nearby organs or tissues within the abdomen. Tumour spread may include the peritoneum, lymph nodes, or other abdominal structures.
The presence of tumour cells outside the ovary increases the stage of the tumour.
Intact versus ruptured ovary
Whether the ovary was intact or ruptured at the time of surgery is important for staging.
If the tumour is confined to the ovary and the capsule is intact, the cancer may be stage I. If the capsule is ruptured or tumour cells are found on the surface of the ovary, the stage may be higher.
Lymphatic and vascular invasion
Lymphatic and vascular invasion means tumour cells are seen inside small lymphatic channels or blood vessels. This finding increases the risk that tumour cells may spread to lymph nodes or distant organs.
Lymph nodes
Lymph nodes are small, bean-shaped structures in the lymphatic system. They help filter harmful substances from the body and play an important role in the immune system.
In ovarian cancer surgery, lymph nodes from the pelvis and abdomen may be removed and examined under the microscope. These are called regional lymph nodes. They include the pelvic and para-aortic lymph nodes.
If tumour cells are found in these lymph nodes, the cancer is considered to have spread beyond the ovary, and the tumour stage increases. Lymph node involvement may also influence treatment decisions, such as the use of chemotherapy or other systemic therapies.
When tumour cells are found in lymph nodes, the pathology report often describes the size of the tumour deposits. The size helps doctors determine the extent of lymph node involvement.
Isolated tumour cells (ITCs)
These are very small clusters of tumour cells measuring 0.2 mm or less. When only isolated tumour cells are present, the lymph nodes are often reported as N0(i+), meaning that only very small deposits of tumour cells were found.
Small lymph node metastases
These tumour deposits measure more than 0.2 mm but 10 mm or less. These are considered true lymph node metastases, indicating that the cancer has spread to the lymph nodes.
Large lymph node metastases
These tumour deposits measure more than 10 mm. Larger tumour deposits generally indicate greater tumour involvement of the lymph node.
Your pathology report may also describe:
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the number of lymph nodes examined
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the number of lymph nodes containing tumour cells
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the location of the involved lymph nodes
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the size of the largest tumour deposit
These findings are important because they help determine the pathologic stage of the tumour, which guides treatment decisions and helps estimate prognosis.
How do doctors stage ovarian cancer?
Staging describes how far a cancer has spread in the body. For ovarian cancer, two main systems are used: the TNM and FIGO systems. Both are internationally accepted and provide important information about prognosis (the expected outcome) and treatment planning.
The TNM system
The TNM system was developed by the American Joint Committee on Cancer (AJCC). It looks at three main factors:
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T (tumour): Describes the size of the tumour and how far it has spread in or around the ovary or fallopian tube.
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N (lymph nodes): Describes whether cancer cells have spread to nearby lymph nodes.
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M (metastasis): Describes whether cancer has spread to distant parts of the body.
Breakdown of the T stage:
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T1: The tumour is limited to one or both ovaries or fallopian tubes.
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T1a: Tumour is inside one ovary or fallopian tube, with the outer surface intact and no cancer cells in fluid taken from the abdomen.
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T1b: Tumour is inside both ovaries or fallopian tubes, but the outer surfaces are intact, and no cancer cells are found in the fluid.
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T1c: The tumour is limited to one or both ovaries or tubes, but there has been a rupture, tumour on the outer surface, or cancer cells found in abdominal fluid.
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T2: The tumour has grown into tissues in the pelvis, such as the uterus or bladder.
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T2a: Spread to the uterus or other fallopian tube or ovary.
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T2b: Spread to other pelvic tissues.
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T3: The tumour has spread beyond the pelvis into the abdomen or to regional lymph nodes.
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T3a: Cancer cells are found microscopically outside the pelvis or in nearby lymph nodes.
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T3b: Visible tumour deposits up to 2 cm outside the pelvis or in nearby lymph nodes.
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T3c: Visible tumour deposits larger than 2 cm outside the pelvis or involving the capsule of the liver or spleen (without entering the organ itself).
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Breakdown of the N stage:
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N0: No cancer cells are seen in regional lymph nodes.
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N0(i+): Only isolated tumour cells smaller than 0.2 mm are seen in the lymph nodes.
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N1: Cancer cells are found in regional lymph nodes.
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N1a: Deposits up to 10 mm.
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N1b: Deposits larger than 10 mm.
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The FIGO system
The FIGO (International Federation of Gynecology and Obstetrics) system is specifically designed for gynecologic cancers like ovarian cancer. It uses similar criteria to the TNM system but is grouped into broader stages that are easier to interpret clinically.
Breakdown of FIGO stages:
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Stage I: Cancer is limited to the ovaries or fallopian tubes.
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IA: In one ovary or fallopian tube only.
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IB: In both ovaries or fallopian tubes.
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IC: Cancer is still limited to the ovaries or tubes, but there has been a rupture, tumour on the surface, or cancer cells found in fluid.
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Stage II: Cancer involves one or both ovaries or tubes with spread to pelvic organs such as the uterus, bladder, or rectum.
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IIA: Spread to the uterus or other ovary/tube.
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IIB: Spread to other pelvic tissues.
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Stage III: Cancer has spread outside the pelvis into the abdominal cavity or to regional lymph nodes.
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IIIA1: Cancer in lymph nodes only.
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IIIA2: Microscopic spread outside the pelvis.
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IIIB: Visible spread outside the pelvis up to 2 cm.
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IIIC: Visible spread larger than 2 cm or spread to the capsule of the liver or spleen.
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Stage IV: Cancer has spread to distant organs outside the abdomen.
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IVA: Cancer cells are found in the fluid around the lungs.
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IVB: Cancer has spread to organs such as the liver, spleen, or lymph nodes outside the abdomen.
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Why staging is important
Both TNM and FIGO staging systems provide doctors with essential information about how far the cancer has spread. This helps guide treatment decisions, such as whether surgery alone is sufficient or whether chemotherapy or other treatments are needed.
Staging also helps predict prognosis. Early-stage disease (stage I) has a much better survival rate compared to advanced-stage disease (stage III or IV). By using staging information, doctors can personalize care and discuss treatment options and expectations with patients.
Questions to ask your doctor
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What stage is my ovarian cancer?
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Was the tumour confined to the ovary or had it spread beyond the ovary?
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Was the ovarian capsule intact or ruptured?
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Were lymph nodes involved?
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Were biomarker tests performed, and what do the results mean?
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Do my biomarker results affect treatment options?