Colon: Neoplastic Disease: CT Evaluation of Abdominal Lymphoma: Colonic Involvement
Elliot K. Fishman, M.D.
Staging and Therapeutic Choices
The therapy of lymphoma (both Hodgkin and non-Hodgkin) is now very effective, with a substantial fraction of patients being cured. However, the prognosis and type of therapy is dictated by the histology and the stage of disease. Although the histopathologic subtype of Hodgkin disease correlates with the stage of disease, it does not correlate with prognosis if stage is taken into account. Conversely, the histologic subtype of non-Hodgkin lymphoma strongly impacts on prognosis and treatment strategies. The current universally accepted International Working Formulation classification and the Rappaport equivalent are shown in Table 1. Although there are minor differences in the clinical presentation and course for the subtypes of non-Hodgkin lymphoma within each of the three categories listed, the lymphomas within each category can generally be approached similarly. In addition, follicular large cell and diffuse small cleaved lymphoma (D and E) can probably be regarded as low-grade lymphomas, while diffuse mixed small and large cell lymphomas (F and G) can be approached as high-grade lymphomas. High-grade lymphomas are aggressive, fast-growing malignancies that are rapidly fatal if not treated; however, about half of the patients can be cured with current treatment. Conversely, low-grade lymphomas are slow growing diseases, with long survivals (median about 7 years), even if untreated. Interestingly, however, with the exception of localized disease, low-grade lymphomas are incurable.
Table 2 shows the staging system for lymphomas (2). Radiotherapy has been the standard treatment for all early stage lymphomas with cure rates ranging from about 50% for both low-grade (3) and high-grade (4) non-Hodgkin lymphomas to over 80% for Hodgkin disease (5). Stage III-IV Hodgkin disease and high-grade non-Hodgkin lymphoma require intensive combination chemotherapy with rates around 50% (6-7). Bulky early stage disease also requires chemotherapy for cure. Hence, adequate staging is critical for determining the correct treatment of both Hodgkin and non-Hodgkin lymphoma.
The treatment of stage I or II Hodgkin disease by radiation therapy includes super voltage radiotherapy using a 4-8 MeV linear accelerator to deliver wide field radiation. The treatment is given through a mantle field to include the lymph nodes of the neck, axilla and mediastinum in one contiguous treatment volume. Four blocks are used to shield the normal lung tissue and an irregular field calculation provides a homogeneous dose distribution to the lymph nodes. The field is tailored to treat the paraaortic nodes and parasplenic nodes and to avoid normal tissue such as kidney and liver. Careful gap calculation is necessary between the mantle and paraaortic fields. Radiation therapy in non-Hodgkin lymphoma is reserved for stage I patients or in combination with chemotherapy for advanced disease. The dosage delivered is dependent on the histologic type of non-Hodgkin lymphoma.
TABLE 1 Histologic Classification of Non-Hodgkin Lymphoma
International Working Formulation Rappaport
Low Grade
A. Small lymphocytic Well-differentiated lymphocytic
B. Follicular, predominantly small-cleaved Nodular poorly differentiated
lymphocytic
C. Follicular, mixed small cleaved and large cell Nodular mixed
Intermediate Grade
D. Follicular, predominantly large cell Nodular histiocytic
E. Diffuse, small cleaved Diffuse poorly differentiated
lymphocytic
F. Diffuse, mixed small cleaved and large cell Diffuse mixed
G. Diffuse, large cell
High Grade Diffuse histiocytic lymphoblastic
H. Large cell, immunoblastic
I. Lymphoblastic
J. Small, non-cleaved Undifferentiated
TABLE 2 Ann Arbor Staging Classification of Lymphoma
Stage
I. Involvement of a single lymph node region.
II. Involvement of two or more lymph-node regions on the same side of the diaphragm (II), which may be accompanied by localized involvement of an extra-lymphatic organ or sit (IIE).
III. Involvement of lymph node regions on both sides of the diaphragm (III), which may also be accompanied by involvement of the spleen (IIIS) or by localized involvement of an extra-lymphatic organ or site (IIIE).
IV. Diffuse or disseminated involvement of one or more extra-lymphatic organs for tissues, with or without associated lymph node involvement.
Abdominal Involvement
Liver
Infiltration of the liver will occur in up to 16% of patients with non-Hodgkin lymphoma and 10% of patients with Hodgkin disease at time of presentation. In autopsy series, about 50% of patients with either Hodgkin disease or non-Hodgkin lymphoma will have hepatic involvement. In rare cases, lymphoma may arise as a primary tumor of the liver. Pathologically, Hodgkin disease is commonly a diffuse infiltrating process while non-Hodgkin disease may present as either a diffuse infiltrating process or with discrete tumor nodules. Spiral CT is more successful at detection of liver involvement than non-spiral CT. The use of dual phase imaging may be useful although no large series of the value of arterial or portal venous phase imaging has been published. We routinely image the liver in the portal phase. The CT appearances of hepatic lymphoma can be divided into three categories:
• Solitary hepatic mass --- this mass may be indistinguishable in appearance for metastatic disease from any source or from primary hepatocellular carcinoma. The lesions may range in size from less than 1 cm to approximately 10 cm in size. Calcification is rare within these lesions unless the patient has had prior radiation therapy. Occasionally, these lesions can bleed and patients may present with an acute abdomen as a presenting sign of tumor involvement.
• Multifocal hepatic lesions --- its appearance can again be similar to metastatic disease or multifocal hepatoma. The lesion size is variable but typically the lesions are in the range of 1-5 cm.
• Diffuse hepatic involvement --- the diffuse infiltration of the liver by hepatoma is the most difficult appearance for detection by CT scans. The lesions are often isodense with hepatic parenchyma or the appearance may be suggestive of fatty infiltration or parenchymal disease rather than tumor infiltration.
Spleen
Splenic lymphoma can be classified as either primary splenic lymphoma or lymphomatous involvement as part of more systemic involvement. Primary splenic lymphoma is rare. When it does occur it is usually a large-cell lymphoma. Non-Hodgkin lymphoma is the most common primary tumor of the spleen. Primary splenic lymphoma may present with associated nodal disease in the splenic, hilar or paraaortic nodal chains.
The CT appearance as well as the clinical presentation (fever, left upper quadrant pain, malaise) of primary splenic lymphoma and splenic abscess can be similar. One helpful differential diagnosis point is that splenic abscesses rarely occur with concurrent adenopathy.
One of the weaknesses of any noninvasive imaging study has been in the accurate detection of splenic involvement by lymphoma. This has in part been due to the fact that most tumors are either infiltrative or present as tumor foci well under a centimeter in size. Absolute measurements of splenic size are of limited value with up to 30% of enlarged spleens in lymphoma being free of tumor. Another study found a sensitivity of 38% and a specificity of 61% for either physical exam or imaging study detection of splenic lymphoma based on organ enlargement.
The CT appearances of splenic lymphoma mirror the variety of pathologic appearances. They include:
• homogeneous enlargement without a discrete mass
• solitary mass
• multifocal lesions
• diffuse infiltration - the appearance on CT typically is one of diffuse
low density areas or diffuse irregularity of splenic enhancement.
Kidney
Renal involvement by lymphoma has been documented in autopsy series to occur in up to one-third of cases. In 75% of these cases, involvement was bilateral. The majority of patients represent non-Hodgkin lymphoma although the CT appearance is indistinguishable from Hodgkin lymphoma.
Renal involvement represents stage IV disease. With the use of contrast enhanced CT the majority of these lesions can be detected. Renal involvement of lymphoma is usually secondary either to hematogenous or lymphatic dissemination. The CT appearance of renal involvement by lymphoma can be classified into four categories:
• Solitary mass. The tumor is usually in a normal sized kidney and may occur with or without associated paraaortic adenopathy. The lesion may appear isodense to normal kidney on noncontrast CT and is best detected on contrast enhanced studies.
• Multiple masses. The multiple nodules are usually bilateral and variable in size. The nodules typically range between 1 and 4.5 cm. The kidney is usually enlarged but may occasionally be normal in size.
• Infiltration of kidney. The kidney is partially or totally replaced by tumor. The kidneys are usually enlarged with decreased renal function not uncommon.
• Infiltration by contiguous retroperitoneal disease. The kidney is directly invaded or engulfed by adjacent tumor and/or nodes. In cases with massive adenopathy the renal outline may be lost or poorly defined. This is especially true in patients with lymphomatous infiltration of the perirenal space. Renal function may be absent in these cases and the patients can present clinically with renal failure.
Depending on the specific CT appearance, renal lymphoma can look similar to renal cell carcinoma, metastasis, pyelonephritis or focal abscess. Primary lymphoma of the kidney is rare due to the lack of lymphoid tissue within the kidney.
Adrenal Glands
Autopsy involvement of the adrenal glands has been reported is up to 25% of patients with lymphoma. The majority of cases are seen with associated bulky lymphadenopathy although primary adrenal lymphoma can occur. Bilateral involvement is common, with adrenal insufficiency or hemorrhage a possible clinical presentation. Adrenal gland involvement is more common in non-Hodgkin lymphoma. One classic appearance of adrenal lymphoma is enlarged glands that maintain their adrenal (arrowhead) configuration.
Stomach
The stomach is the most frequent site of lymphomatous involvement of the GI tract. Non-Hodgkin lymphoma accounts for approximately 80% of cases. In an early review of 23 patients with gastric lymphoma, Megibow found an average gastric wall thickness of 5 cm (range 2.5-8 cm) although in our experience we are now detecting gastric lymphoma when the tumor is less bulky. Classic patterns of involvement include:
• diffuse infiltration involving greater than 50% of the length
of the stomach
• segmental infiltration
• localized polypoid form
The latter form is often associated with an ulcer. Tumor infiltration is usually homogeneous although low density regions may be seen. Most patients with gastric lymphoma will have associated adenopathy. One of the key differential diagnosis points between gastric lymphoma and adenocarcinoma is that in lymphoma the nodes are usually bulkier and extend beneath the renal hilum.
Small Bowel and Mesentery
The small bowel is the second most frequent site of GI tract involvement by lymphoma. Lymphomas constitute approximately one-half of all primary malignant small bowel tumors. The ileum is the most common site of occurrence, the duodenum the least frequent. The clinical presentation is variable ranging from bowel obstruction, intussusception or perforation to a sprue-like syndrome. Simultaneous multifocal sites of involvement is not uncommon. The CT appearance of lymphoma is variable. The typical appearances can be classified as aneurysmal, constrictive, nodular and ulcerative.
Mesenteric involvement by lymphoma may directly involve the small bowel by direct extension, or indirectly by displacement due to mass effect. Although mesenteric involvement may be an isolated finding it is usually seen as part of a more systematic involvement. Mesenteric involvement can be represented by any of the four general patterns of mesenteric disease: rounded masses, ill-defined masses, cake-like masses and stellate mesentery. The rounded mass appearance is the most common and is usually seen with non-Hodgkin lymphoma. Discrete mesenteric nodes may directly involve/encase small bowel with a classic "sandwich" appearance having been described.
Lymphomatous involvement of the GI tract is more common in the immunocompromised patient who develops lymphoma especially in renal transplant patients and in the AIDS patient. In nearly all cases the pathology was non-Hodgkin lymphoma. The incidence of non-Hodgkin lymphoma in renal transplant patients is 35 times greater than for the general population. De novo malignancies affect 6% of renal transplant recipients. Non-Hodgkin lymphoma accounts for more than 20% of transplant-related malignancy. The CT appearance of NHL in the immunocompromised host is indistinguishable from lymphoma in the immunocompromised host. However, post-transplant lymphomas involve extranodal sites more frequently, especially the central nervous system. In patients with renal transplant the transplant kidney was the organ most often infiltrated by tumor.
Colon
Primary colonic lymphoma is uncommon and is responsible for less than 0.1% of primary rectal tumors. The cecum and rectum are the most common sites of involvement. Non-Hodgkin lymphoma is the most frequent histology in these cases. Primary colonic lymphoma presents as either a focal form or diffuse form. The focal form is often a polypoid mass, not uncommonly in the cecum. Occasionally, this can lead to an intussusception. The CT appearance is similar to a primary adenocarcinoma of the colon. The diffuse form is variable with infiltration of variable lengths of colon. Ulcerations, strictures of fistulae formation may occur. Diffuse infiltration is often associated with abdominal adenopathy or extensive bowel infiltration by tumor. The patient with colonic infiltration may present with an acute abdomen due to colonic perforation. Primary colonic lymphoma appears to be more common in the patient with AIDS. Primary colonic lymphoma may look like a severe colitis in select cases.
Pancreas
Although up to one-third of patients with non-Hodgkin lymphoma will demonstrate pancreatic involvement on post-mortem examination, primary involvement of the pancreas is rare. Primary pancreatic lymphoma is usually difficult to distinguish from pancreatic infiltration by peripancreatic nodes. Nodes in the pancreaticoduodenal chain can in fact simulate a pancreatic mass. Fortunately, there is no difference in therapy for pancreatic vs. peripancreatic lymphoma.
Pancreaticoduodenal lymph nodes lie between the duodenal sweep and the pancreatic head. The nodes can be confused with enlargement of the pancreatic head. Pancreaticoduodenal nodes can result from colon carcinoma, lung carcinoma, breast and gastric cancer in addition to lymphoma.
Conclusion
Computed tomography continues to remain the study of choice for the staging and follow-up in the patient with lymphoma. Since every organ system can be involved by this disease process (with a variety of appearances), it is important for one to carefully and systematically analyze all CT scans to detect the true extent of disease.