Colon: Neoplastic Disease: Metastatic Cancer: Classic CT Patterns of Dissemination

Introduction

CT scanning is the modality of choice for the staging of most neoplasms. CT scanning can rapidly and efficiently survey the entire body in the search for metastatic disease. Knowledge of common patterns of dissemination of specific neoplasms is vital for accurate detection and staging. Pattern recognition is also important for suggesting the underlying primary tumor in cases of unknown primary, or when multiple sites are involved and the organ of origin is unclear. This essay reviews some of the common, classic patterns of metastatic disease demonstrated at CT evaluation.


Overview

Over 50% of patients with newly diagnosed cancer have metastatic disease present at initial diagnosis . Tumors often disseminate in a predictable and reliable fashion, either proliferating at the first site encountered, or bypassing proximal organs in search of a milieu favorable to metastatic growth . Metastatic dissemination results from a complex series of tumor-host interactions, including cellular invasion, vascular intravasation, circulation, tumor arrest, tumor growth, and angiogenesis . Unusual patterns of metastatic spread, not explained from anatomic considerations alone, is the result of organ tropism: the ability of different tumors to exhibit specific and unique attachment factors, probably via specific tumor surface receptors . Tumors can spread in a variety of channels. The most common pathway is contiguous invasion of adjacent structures via infiltration of tissue spaces. The most common pathways for distant spread in the chest and abdomen are the lymphatics, blood vessels, and epithelial and coelomic cavities.

Lymphatics are entered relatively easily by tumor cells, as lymphatic vessels lack a basement membrane . Tumor cells can then embolize to regional lymph nodes before disseminating into the venous system via lymphaticovenous connections . Axillary and internal mammary lymph node involvement by breast cancer is a classic example of lymphatic dissemination. As tumor cells obstruct lymphatic drainage, retrograde lymphatic spread can occur to additional locations such as the liver, skin, and distant lymph nodes. Tumor involvement of the thoracic duct is especially notorious for altering lymph node, often resulting in widespread retrograde dissemination of cancer cells .

Another pathway of tumor spread is vascular invasion, either arterial or venous. Venous invasion is most common, and typically occurs at the sit e of the primary tumor capsule . Metastases are then embolized to drainage organs where cell arrest can occur, typically at the first capillary bed encountered. Classic examples include the lung for systemic venous emboli, the liver for portal venous emboli, and the peripheral body tissues for arterial emboli. Retrograde venous seeding is also possible, most notably in the paravertebral plexus, which because of it’s valveless nature can allow unmitigated tumor cell dissemination from the head to the pelvis . Tumors which can spread via this route are able to bypass the portal and pulmonary systems before dissemination. Classic examples are prostate, breast, renal and lung cancers.

Coelomic cavities involved in tumor dissemination include the pleural space of the thoracic cavity and the peritoneal spaces of the abdomen and pelvis. The most commonly involved is the peritoneum, which carries tumor cells in ascitic fluid. The distribution of intraperitoneal metastases often corresponds to predictable flow patterns, the most classic example of which is seen with ovarian cancer . With this tumor, or any tumor demonstrating intraperitoneal spread, the paracolic gutters, cul-de-sac, omentum, and liver surface are common sites of metastases. In the chest, pleural dissemination typically spreads via gravitational forces and is often seen in the lower thoracic cavity .


Pattern of dissemination: lower neck

Common primaries: head and neck, lymphoma, esophagus, stomach Lower cervical adenopathy can result from metastatic tumors of the head and neck, most commonly tumors of the pharynx, oral cavity, and supraglottic larynx . Supraclavicular nodes are also frequently encountered in patients with lung cancer, and represent stage IV disease. Lymphoma is also commonly encountered in the neck. Supraclavicular lymph node metastases can also represent a site of dissemination at some distance from the primary tumor. For example, tumors of the esophagus and stomach can spread via the thoracic duct to drain into the left supraclavicular nodes (the so-called "Virchow’s" node). Cervical or supraclavicular lymph node metastases occur more frequently with upper third esophageal carcinomas.


Pattern of dissemination: internal mammary nodes

Internal mammary adenopathy is an important site of occult metastasis in breast cancer. Involvement is often ipsilateral to the primary tumor and represents a site of regional nodal spread, much like the axilla. Lymphoma represents the other common malignancy to selectively target this nodal chain. Involvement is usually the result of contiguous spread from the anterior mediastinal or paratracheal area to the other mediastinal lymph node groups, including the internal mammary chain. Occasionally, isolated internal mammary nodal involvement is seen.

Common primaries : breast, lymphoma


Pattern of dissemination: mediastinum

Common tumors to involve the mediastinum include bronchogenic carcinoma and lymphoma. In general, the larger and more central the primary lung tumor, the higher the prevalence of mediastinal lymph node involvement. One exception is small cell lung cancer, which can present with bulky mediastinal nodes even in the presence of a small or even grossly undetectable lung primary. Lymphoma classically presents as a bulky anterior mediastinal mass, which can be massive. Another relatively common tumor to metastasize to the mediastinum is breast cancer, often in continuity with an internal mammary nodal mass. In practice, almost any tumor can metastasize to the mediastinum. Without a known primary, histologic confirmation is often necessary.

Common primaries :lung, breast, lymphoma

Direct lymphatic connection from the renal lymphatics to the thoracic duct and mediastinum exist, accounting for the classic but uncommon finding of metastatic renal cell cancer to the mediastinal or hilar lymph nodes, especially on the right side.

Pattern of dissemination: lung parenchyma

Pulmonary metastases occur in 30% of all malignancies, usually through hematogenous dissemination. In 10-25% of cases, the lungs are the only site of metastasis. The classic CT appearance is that of multiple well-defined nodules, often seen in continuity with an underlying blood vessel. Lung metastases are typically widespread, although solitary metastases are not at all uncommon, particulary in colon, kidney, breast, testicular, and musculoskeletal primaries. It is often possible to narrow a differential diagnosis based upon the appearance of metastastic lung nodules. Discrete cavitary nodules are most commonly seen with squamous cell primaries, especially a head and neck tumor in men and cervical cancer in women. "Fuzzy" nodules may indicate a hemorrhagic primary such as renal cell carcinoma or choriocarcinoma, or treated lesions. Miliary nodules are characteristic of metastatic thyroid cancer, melanoma, and adenocarcinoma. A reticulated, "beads-on-a string" appearance suggests lymphangitic spread of tumor, especially common in metastatic lung or breast cancer.

Common primaries:Based on appearance

Pattern of dissemination:pleural space

Metastases constitute the most common tumor to involve the pleura. Involvement can be unilateral or bilateral. Metastatic adenocarcinoma is the most frequent cell type to metastasize, with lung and breast cancer most common. Spread is either by direct spread or lymphatic dissemination. Classic findings include small, lenticular masses and pleural thickening. An associated pleural effusion is often demonstrated. Other tumors which can involve the pleural space include invasive thymoma and lymphoma. Invasive thymomas invade the mediastinum and seed the pleural space directly. Spread from thymomas are usually confined to one hemithorax. Both lymphoma and thymoma can present as well-defined, lobulated pleural implants without associated pleural fluid.

Common primaries :adenocarcinoma, thymoma, lymphoma

Pattern of dissemination: liver

The liver is second in frequency to the lungs as the most common site of metastases. The CT appearance of liver metastases is very dependent on lesion vascularity, histology, and the presence or absence of necrosis, hemorrhage, and calcification. Therefore, a tremendous spectrum of appearances are possibly, even with differing foci of the same tumor. In general, most metastases are hypovascular and appear relatively hypoattenuating, and are best appreciated during the portal-venous phase of contrast-enhancement. Such tumors have classically disseminated to the liver via portal venous emboli: colon cancer is by far the most common tumor to do so. Less common are the hypervascular tumors, which appear as hyperattenuating foci against the normal liver and are best appreciated during the arterial phase of contrast enhancement. Classic hypervascular primaries include pancreatic islet cell tumor, carcinoid tumor, and renal cell cancer. Calcification is typically demonstrated in metastases from mucinous tumors such as colon or stomach cancer, or other primary tumors including ovarian, breast, and thyroid cancer. Necrotic metastases are characteristic of metastatic sarcomas, melanoma, and mucinous tumors of the colon or ovary.

Common primaries :Based on appearance

Pattern of dissemination: gastrohepatic ligament /celiac axis

Metastatic esophageal carcinoma can present in nodes from the supraclavicular region to the celiac nodal chains. Tumors located in the distal third of the esophagus most commonly spread to the regional lymph nodes in the gastrohepatic ligament and celiac axis. Adenocarcinoma of the stomach is another common primary to involve this region. Lymphoma is often in the differential diagnosis.

Common primaries:Esophagus, stomach

Pattern of dissemination: pancreas

Metastases to the pancreas are uncommon. When they do occur, most commonly the primary tumor arises from the kidney, lung, breast, or GI tract. Melanoma can also metastasize to the pancreas. Usually, the diagnosis is suggested by the presence of multiple pancreatic masses in a patient with a known primary. When solitary, however, the appearance can be indistinguishable from primary pancreatic carcinoma. Lymphoma can also present with peripancreatic lymphadenopathy that can mimick a pancreatic cancer.

Common primaries: Kidney, lung, melanoma

Pattern of dissemination: spleen

Metastases to the spleen most often result from hematogeneous dissemination. Metastases typically appear as multiple nodules, although solitary masses are not uncommon. The most common primary malignancies to metastasize to the spleen are lung and breast. Melanoma has the highest incidence of involvement on a per primary basis, seen in up to 30% of patients at autopsy . Cystic metastases can occur with breast, ovary, and melanoma primaries. Calcifications are common in patients with a mucinous adenocarcinoma primary, particularly colon and ovary.

Common primaries: adenocarcinoma, ovary, melanoma

Pattern of dissemination: adrenals

Adrenal gland metastases constitute up to 25% of all adrenal tumors. Involvement is commonly by hematogenous dissemination. Metastases can be unilateral or bilateral. Lesions tend to be well circumscribed and of soft-tissue attenuation. Size can vary from small to very large. Lung cancer is the most common primary, with adrenal metastases found in up to 20% of patients . Other relatively common primary sites include the breast, kidney, colon, pancreas, esophagus and thyroid. Of these, kidney and breast cancer are most common. Metastatic spread of renal cell carcinoma with ipsilateral involvement of the adrenal gland occurs in up to 10% at surgery Lymphoma can also involve the adrenal glands; the adrenals will typically maintain an adreniform shape; bilateral involvement is seen in 1/3 of cases.

Common primaries: Lung, breast, kidney

Pattern of dissemination: peritoneum / omentum

Disseminated carcinomatosis to the peritoneum and omentum occurs when tumors penetrate beyond the primary organ of origin to spread directly along the adjacent peritoneal surfaces. Tumors of the stomach, colon, pancreas, and ovary are most common to do so. The appearance of dissemination can produce a distinctive appearance ranging from stranding to small nodules to discrete masses. The transverse mesocolon, gastrocolic ligament, and gastrosplenic ligament are important pathways of tumor spread for stomach and colon primaries. Ovarian cancer spreads diffusely along all mesothelial surfaces. Ovarian cancer metastases often produce a "scalloped" appearance to the adjacent solid organs, and may calcify.

Common primaries :Ovary, colon, stomach

Pattern of dissemination: small bowel

Lung cancer and melanoma represent the most common primary tumors to metastasize to the small intestine. Involvement is typically by hematogenous dissemination of tumor. Other common primaries to seed the small intestine include the kidney and breast. Metastatic lesions present as well defined masses within the bowel lumen. Intussusception may be the presenting finding at CT evaluation. Intraperitoneal seeding and direct invasion represent other pathways for small bowel metastases. Lymphoma can also commonly involve the small bowel. Common primaries: Lung, melanoma, lymphoma

Pattern of dissemination: kidney

Metastases to the kidney are not rare. Involvement is typically via hematogenous dissemination. Common primary tumors include lung, breast, colon, melanoma. Most metastases are small and hypovascular, enhancing less than normal renal parenchyma following contrast administration. Larger lesions can be indistinguishable from renal cell carcinoma. A distinguishing feature of primary renal tumors is renal vein invasion, which is very rare with metastases. Lymphomatous involvement of the kidneys is also quite common. Multiple masses, a solitary mass, or diffuse renal enlargement are typical CT patterns of lymphoma.

Common primaries: Lung, lymphoma

Pattern of dissemination: ovary

Metastatic involvement of the ovaries should always be considered in the differential diagnosis of patients with bilateral adnexal masses. Krukenburg tumors, classically described from metastatic adenocarcinoma of GI primary, can mimic the CT and sonographic appearance of primary ovarian cancer and present as the initial site of involvement. Involvement is typically by hematogenous dissemination of tumor. Other possible primary tumor sites include the breast and lung.

Pattern of dissemination: retroperitoneum

Retroperitoneal adenopathy is a very common finding in metastatic dissemination from a multitude of possible primaries, as well as lymphoma. Adenocarcinoma is most common solid organ primary, and common sites include the colon, stomach, pancreas, lung, and breast. At times the primary remains "unknown" even after exhaustive work-up. Pelvic tumors, such as prostate or endometrial cancer, can bypass pelvic nodes and also present with paraaortic nodes. One characteristic tumor metastasis from testicular cancer, which typically shows initial retroperitoneal drainage into a "sentinal" node located in the renal perihilar region. Tumor spread is commonly unilateral. Nodes may demonstrate low attenuation from intratumoral necrosis, especially bulky nodes from seminoma or embryonal carcinomas. .

Common primaries:Adenocarcinoma (GI tract)

Common primaries: Adenocarcinoma, lymphoma

Pattern of dissemination: pelvic lymph nodes

Pelvic nodal metastases are most commonly seen with disseminated pelvic primaries, as well as lymphoma. Pelvic tumors, such as endometrial and cervical cancer, spread along the uterine vessels to the internal, external, and common iliac nodes. Prostate cancer typically spreads first to the hypogastric and obturator nodes, and less commonly to external iliac lymph nodes. Bladder cancer spreads through the major lymphatic trunks that drain into the external iliac node chain. Tumors from the posterior bladder wall may drain into the internal iliac chain.

Common primaries:prostate, cervix, lymphoma

Pattern of dissemination: subcutaneous tissues

Metastatic nodules in the subcutaneous tissue are typically the result of hematogenous dissemination. Common primaries include melanoma, lymphoma, or adenocarcinoma from primaries such as the lung, kidney, or breast. Multisystemic involvement is a hallmark or lymphoma and melanoma, and a careful search of the subcutaneous tissues should be part of every CT evaluation.

Common primaries: Melanoma, lymphoma, adenocarcinoma

Note:this review is based on an exhibit from Urban BA et al.