Types of Rectal Cancer

Rectal cancer develops when abnormal cells grow in the rectum, the final portion of the large intestine. Although the term “rectal cancer” often refers to adenocarcinoma, several other types of cancer can arise in the rectum. The types are classified based on the cells or tissues where they begin. Accurately identifying the type of rectal cancer is an essential step in understanding how the tumor may behave and developing an appropriate treatment plan.

Rectal adenocarcinoma

Rectal adenocarcinoma begins in the glandular epithelial cells that produce mucus in the inner lining (mucosa) of the rectum. It is by far the most common type of rectal cancer, accounting for more than 9 out of 10 diagnoses. Many rectal adenocarcinomas develop after abnormal cells accumulate within a precancerous polyp, although not every adenocarcinoma is found alongside a polyp.

The behavior of rectal adenocarcinoma can vary considerably. Some tumors may remain confined to the rectal wall, while others may grow into nearby tissues or spread through lymphatic channels or the bloodstream. When rectal adenocarcinoma metastasizes, common sites include the liver and lungs. The tumor’s stage, grade, molecular features and response to any treatment given before surgery can provide more individualized information than the term “adenocarcinoma” alone.

The symptoms of rectal adenocarcinoma are generally similar to those caused by other types of rectal tumors, such as rectal bleeding, a persistent change in bowel habits, a feeling that the bowel does not empty completely, narrow stools or pelvic discomfort. Some tumors are found through colorectal cancer screening before symptoms develop.

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Subtypes of rectal adenocarcinoma

Most rectal adenocarcinomas are conventional adenocarcinomas, also called adenocarcinomas not otherwise specified. However, based on the tumor’s microscopic appearance, a pathologist may identify a less common subtype, such as:

• Mucinous adenocarcinoma – The tumor contains abundant extracellular mucin, a jelly-like substance surrounding groups of cancer cells. This designation generally applies when mucin makes up more than half of the tumor, and it can affect imaging findings, patterns of spread and treatment planning.
• Signet ring cell adenocarcinoma – The tumor contains cancer cells filled with mucin, which pushes the nucleus to one side, creating a ringlike appearance under a microscope. This uncommon subtype often has a more aggressive clinical course and may be diagnosed at a more advanced stage.
• Medullary carcinoma – The tumor is composed of sheets of abnormal cells accompanied by prominent immune cells. In colorectal cancers, this rare subtype is often associated with deficient mismatch repair and is much more likely to arise in the colon than in the rectum.
• Adenosquamous carcinoma – The tumor contains both gland-forming and squamous cancer cells. Because this subtype is exceptionally rare, an expert pathology review can be especially valuable before treatment begins.

For localized rectal adenocarcinoma, treatment may include chemotherapy, radiation therapy and surgery, with the sequence tailored to the tumor’s location, stage and other features. A patient with a complete clinical response after treatment may be a candidate for carefully structured nonoperative management. Biomarker findings can also influence systemic therapy, particularly for cancer that has spread or cannot be removed surgically.

Rectal neuroendocrine neoplasms

Rectal neuroendocrine neoplasms begin in specialized neuroendocrine cells that receive nerve signals and can release hormones. Many are discovered incidentally during a colonoscopy or another examination and cause no symptoms. Unlike certain neuroendocrine tumors in other organs, rectal neuroendocrine tumors seldom produce enough hormone to cause a recognizable hormonal syndrome, such as flushing or diarrhea.

Rectal neuroendocrine neoplasms are divided into biologically distinct categories:

• Well-differentiated neuroendocrine tumors (NETs) – The tumor cells resemble normal neuroendocrine cells and are graded according to how actively they are dividing. Small, low-grade NETs confined to the rectal wall often grow slowly and may be removed through an endoscope or a local surgical procedure. Larger, higher-grade or invasive tumors generally have a greater chance of spreading, particularly to lymph nodes or the liver.
• Poorly differentiated neuroendocrine carcinomas (NECs) – These tumors have highly abnormal cells, grow rapidly and are more likely to spread early. Small cell and large cell neuroendocrine carcinoma are the principal types of NECs, and their treatment typically relies on systemic chemotherapy rather than the standard treatment pathway for rectal adenocarcinoma.
• Mixed neuroendocrine-nonneuroendocrine neoplasms (MiNENs) – These tumors contain a neuroendocrine component and a separate nonneuroendocrine cancer component, most often adenocarcinoma. The proportion, grade and behavior of each component can help guide treatment.

The size, depth and grade of the tumor are central to evaluating a rectal neuroendocrine neoplasm. For a well-differentiated NET, a pathologist will determine the grade by assessing how many tumor cells are dividing under a microscope and calculating the Ki-67 proliferation index, which is the percentage of tumor cells that test positive for a protein associated with cell division. These findings can indicate how quickly the tumor is growing and help determine whether local removal or more extensive treatment may be appropriate.

Other rare types of rectal cancer

Several other cancers can begin in the rectum, but together they represent only a small fraction of rectal cancer diagnoses. Determining that a tumor is truly a primary rectal cancer may require the pathologist and healthcare team to rule out a cancer that began in a nearby structure or spread to the rectum from another site.

Rare types of rectal cancer include:

• Rectal squamous cell carcinoma – This type of rectal cancer begins in flat squamous cells rather than glandular cells. A primary squamous cell carcinoma of the rectum is exceptionally rare, and the diagnostic evaluation must distinguish it from an anal cancer extending upward or a metastasis from another organ. Treatment often emphasizes chemotherapy and radiation therapy.
• Gastrointestinal stromal tumors (GISTs) – A GIST is a type of soft tissue sarcoma that develops from specialized cells in the gastrointestinal tract wall, known as interstitial cells of Cajal or their precursors. Rectal GISTs are uncommon, and testing the tumor cells for genetic alterations such as KIT and PDGFRA can help determine whether treatment with a targeted drug may be effective.
• Rectal lymphoma – This type of rectal cancer begins in lymphocytes, a type of white blood cell, within lymphatic tissue in the rectum. Most cases are non-Hodgkin lymphomas, and treatment is based on the lymphoma subtype and generally differs substantially from treatment for rectal adenocarcinoma.
• Anorectal melanoma – This rare cancer develops from melanocytes, the pigment-producing cells found in the lining of the anorectal region. When the tumor originates in the rectal mucosa, it is considered a primary rectal melanoma. These tumors may contain little or no visible pigment and can resemble more common rectal or anal conditions, making an expert pathology review particularly important.
• Other rectal sarcomas – These tumors arise in the connective or supportive tissues of the rectal wall. Examples include leiomyosarcoma, which begins in smooth muscle cells, and other exceptionally rare soft tissue sarcomas that require subtype-specific evaluation.

Moffitt Cancer Center’s multispecialty team has expertise in evaluating and treating unusual gastrointestinal tumors. When necessary, the rectal cancer team can collaborate with specialists in neuroendocrine tumors, lymphoma, melanoma or sarcoma to build a plan around the tumor’s underlying biology.

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How the types of rectal cancer are diagnosed

Symptoms, a physical examination and imaging can reveal the presence and extent of a rectal tumor, but they generally cannot establish its exact cell type. That determination usually requires microscopic examination of a tissue sample obtained during a colonoscopy, flexible sigmoidoscopy, local excision or surgery.

Tissue biopsy and pathology review

A pathologist will examine the sampled tissue under a microscope to determine the tumor’s cell type (histology). In the pathology report, the pathologist may also describe how closely the cancer cells resemble healthy cells, whether mucin or signet ring cells are present and how actively the cells appear to be dividing.

Immunohistochemistry can help resolve tumors that do not have a typical appearance. This laboratory technique uses antibodies to detect proteins in the tumor cells, helping the pathologist distinguish adenocarcinoma from a neuroendocrine neoplasm, lymphoma, melanoma, sarcoma or cancer that spread to the rectum from another organ.

Biomarker and molecular testing

Biomarker testing provides information beyond the tumor’s appearance under a microscope. Rectal adenocarcinomas are generally tested for problems with the mismatch repair system, which normally corrects errors that occur when DNA is copied during cell division. A malfunctioning system can cause errors to accumulate in repetitive sections of DNA, a finding known as microsatellite instability. The results can help guide treatment and indicate whether evaluation for Lynch syndrome may be appropriate.

Depending on the stage and clinical circumstances, additional testing may be performed for biomarkers involving KRAS, NRAS, BRAF, HER2, NTRK and other genes or proteins. The results may help the healthcare team identify targeted therapies that could be appropriate. For other tumor types, different tests may be relevant. For instance, the Ki-67 index can help grade neuroendocrine neoplasms, while KIT and PDGFRA testing can guide targeted treatment for GIST.

Imaging and staging tests

Pelvic magnetic resonance imaging (MRI) can provide detailed information about a rectal tumor’s location, depth of growth and relationship to nearby structures. Computed tomography (CT) scans of the chest, abdomen and pelvis can help determine whether cancer has spread, and endorectal ultrasound may be useful for evaluating certain early tumors. Some tumor types may also call for specialized imaging, such as somatostatin receptor imaging for a well-differentiated neuroendocrine tumor or a positron emission tomography (PET) scan in selected clinical situations.

Imaging findings may suggest a particular diagnosis, but imaging does not ordinarily replace a biopsy. The healthcare team will integrate the pathology, molecular test results and imaging findings to confirm the diagnosis, assign the stage and plan treatment.

Frequently asked questions (FAQs) about the types of rectal cancer 

Identifying the type of rectal tumor is an important first step in understanding the diagnosis. The pathology report and staging evaluation provide additional details that help the healthcare team determine what the diagnosis means for the individual patient.

What does adenocarcinoma mean in my rectal cancer pathology report?

The term “adenocarcinoma” means the cancer began in gland-forming cells in the rectal lining. It is the most common type of rectal cancer, but the report may include additional details, such as the tumor’s grade, subtype, mismatch repair status and other biomarkers, that further refine the diagnosis.

Are there different, rare types of rectal cancer besides adenocarcinoma?

Yes. Less common rectal tumors include neuroendocrine tumors and neuroendocrine carcinomas, squamous cell carcinomas, GISTs, lymphomas, melanomas and other sarcomas. These cancers arise from different cells and may require very different treatments.

How does my specific rectal cancer type determine my treatment plan?

The tumor type can help determine which treatments are likely to work. For example, conventional treatment for rectal adenocarcinoma may combine chemotherapy, radiation therapy and surgery, while lymphoma is usually treated with lymphoma-directed systemic therapy and a GIST may respond to a targeted drug.

Can a rectal tumor have more than one cell type?

Yes, although this is uncommon. Adenosquamous carcinoma contains glandular and squamous components, while a mixed neuroendocrine-nonneuroendocrine neoplasm contains both neuroendocrine cancer and another cancer type. Treatment planning considers the identity, grade and extent of each component.

Is the type of rectal cancer the same as its stage?

No. The type identifies the cells or tissue where the cancer began, while the stage describes the extent of the cancer in the body. Both can influence treatment, along with the tumor’s location, grade, molecular features and the patient’s overall health and goals.

Can the type of rectal cancer be determined from an MRI?

An MRI can show where a rectal tumor is located and how far it has grown into nearby tissues, but it usually cannot confirm the tumor’s exact cell type. A biopsy and pathology examination are generally needed for a definitive diagnosis.

Why might a second pathology review change a rectal cancer diagnosis?

Rare tumors and mixed cancers can have overlapping microscopic features. A pathologist who specializes in gastrointestinal tumors may perform an additional tissue review and use immunohistochemistry or molecular testing to clarify the diagnosis and identify details that could affect treatment.

The Moffitt Cancer Center approach to rectal cancer

An accurate diagnosis provides the foundation for individualized rectal cancer treatment. At Moffitt, subspecialized pathologists who focus exclusively on specific organ systems evaluate tumor tissue using advanced pathology techniques and, when appropriate, biomarker and molecular testing. Seeking a second opinion at Moffitt can help confirm the tumor type, reduce the risk of misclassification and ensure that treatment planning begins with the most precise information available.

Each patient’s case can be evaluated by a multispecialty team in Moffitt's Gastrointestinal Oncology Program. Medical oncologists, surgical oncologists, radiation oncologists, radiologists, pathologists and other specialists collaborate to account for the tumor’s histology, stage, molecular profile, exact location and relationship to nearby structures. Patients may also have access to clinical trials evaluating innovative approaches to rectal cancer diagnosis and treatment. As a National Cancer Institute (NCI)-designated Comprehensive Cancer Center, Moffitt combines compassionate patient care with groundbreaking research focused on improving cancer outcomes.

To learn more about the types of rectal cancer, you can request an appointment with a specialist in Moffitt’s Gastrointestinal Oncology Program by calling 1-888-663-3488 or submitting a new patient registration form online. We do not require referrals.