(Radiographics. 2001;21:161-179.)
© RSNA, 2001
Extranodal Hodgkin Disease: Spectrum of Disease1
Ali Guermazi, MD,
Pauline Brice, MD,
Eric de Kerviler, MD ,
Christophe Fermé, MD,
Christophe Hennequin, MD,
Véronique Meignin, MD and
Jacques Frija, MD
1 From the Department of Radiology (A.G., E.d.K., J.F.), the Department of Hematology (P.B.), GELA, the Hayem Center of Hematology (C.F.), the Department of Radiation Therapy (C.H.), and the Department of Histopathology (V.M.), Saint-Louis Hospital, AP-HP, 1 Avenue Claude Vellefaux, 75475 Paris, France. Presented as a scientific exhibit at the 1999 RSNA scientific assembly. Received March 7, 2000; revision requested April 6 and received June 7; accepted June 9. Address correspondence to A.G. (e-mail: guermazi@chu-stlouis.fr).
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Abstract
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Extranodal lesions in Hodgkin disease may develop and spread to virtually any organ system, simulating other neoplastic or infectious diseases. It is important to determine whether extranodal involvement represents a primary manifestation or dissemination of systemic disease, which has a poorer prognosis. Computed tomography (CT) is the preferred modality, although ultrasonography and magnetic resonance (MR) imaging may also be helpful. CT is superior to conventional radiography in assessing chest disease, although MR imaging is more sensitive than CT in detecting chest wall involvement. CT is preferred for evaluating hepatic lymphoma and has proved particularly valuable in diagnosing gastric lymphoma and detecting renal or perirenal masses. CT and MR imaging are equally effective in detecting brain Hodgkin disease; however, the latter is superior in the detection of extracerebral tumor deposits in the subdural or epidural space. MR imaging is also preferred for evaluating meningeal and spinal cord involvement. Both MR imaging and CT allow excellent assessment of bone texture and accurate analysis of tumoral bone invasion, but MR imaging is superior in demonstrating bone marrow infiltration, and CT is superior in delineating the extent of cortical bone destruction. In the future, metabolic positron emission tomography may provide more information about extranodal lymphoma than do the current imaging modalities.
Index Terms: Hodgkin disease, CT, **.1211 • Hodgkin disease, diagnosis, **.3422 • Hodgkin disease, MR, **.12141 • Hodgkin disease, staging, **.342 • Hodgkin disease, therapy, **.342
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LEARNING OBJECTIVES FOR TEST 4
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After reading this article and taking the test, the reader will be able to:
- Identify and describe the radiologic features of diverse forms of extranodal Hodgkin disease.
- List various diagnostic imaging strategies in extranodal Hodgkin disease.
- Discuss the differential diagnosis of extranodal Hodgkin disease.
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Introduction
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Hodgkin disease is a nodal malignancy that is now largely curable. At presentation, Hodgkin disease is usually supradiaphragmatic, with contiguous spread often occurring predictably from one nodal group to the next along the lymphatic pathways. Hodgkin disease is usually almost entirely confined to the lymph nodes. Extranodal involvement is much less common in Hodgkin disease than in non-Hodgkin lymphoma. Extranodal invasion of adjacent tissue is seen in up to 15% of cases and hematogenous spread in 5%–10%. Even when dissemination occurs beyond the lymphoreticular system, certain patterns of associated spread are frequently evident. Extranodal involvement (except in the spleen and thymus) indicates stage IV Hodgkin disease. Initial staging is crucial for demonstrating the presence of extranodal involvement, which will affect therapeutic decisions. First, contiguous (E-stage) disease, which requires local radiation therapy, must be distinguished from stage IV disease, which is treated with chemotherapy alone or combined with general radiation therapy. Second, the extent of extranodal involvement must be evaluated because it is considered prognostic.
In this article, we discuss and illustrate diverse forms of extranodal Hodgkin disease and evaluate the efficacy of various imaging modalities including computed tomography (CT), magnetic resonance (MR) imaging, and ultrasonography (US) in the diagnosis and management of these pathologic conditions. In addition, we discuss differential diagnoses and diagnostic strategies and pitfalls in extranodal Hodgkin disease.
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Prognosis and Therapy
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With recent advances in the treatment of Hodgkin disease, the aim is now to cure affected patients and to limit long-term therapeutic toxicity. Consequently, therapeutic strategies are tailored according to initial prognostic factors. All prognostic scores established for Hodgkin disease take into account either the presence of stage IV disease or the number of extranodal sites (1–3). Therapeutic groups are determined according to biologic factors (eg, anemia, lymphopenia) and the extent of disease (eg, number of lymph nodes or presence of bulky tumor, extranodal involvement, stage IV disease). Stage IV disease is usually less responsive to radiation therapy and can be treated with chemotherapy if the number of cycles is sufficient (4). In contrast, patients with E-stage disease can be treated with less extensive chemotherapy combined with radiation therapy (5).
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Thorax
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Intrathoracic involvement is more common in Hodgkin disease than in non-Hodgkin lymphoma (6,7). The presence and distribution of thoracic involvement in patients with Hodgkin disease is important in both tumor staging and treatment, especially when radiation therapy is planned (7). Currently, there is general agreement that CT is more sensitive and specific than conventional radiography in assessing chest disease (8,9).
Lungs
Involvement of the lung parenchyma is relatively rare in Hodgkin disease (10,11) and accounts for 5.9%–11.6% of cases (6,7,12). It is bilateral in about 4.3% of cases (7). The lung is more frequently involved in secondary or recurrent disease than in primary disease (6,13–15). Pulmonary involvement is usually associated with hilar or mediastinal nodal disease at presentation (6); very few cases of primary pulmonary Hodgkin disease with no hilar or mediastinal node disease have been reported (14–16). In cases of unilateral hilar adenopathy, parenchymal involvement (if present) is seen in the ipsilateral lung (6,7,16). In treated patients, relapse involving the chest is commonly seen in the lungs. Pulmonary involvement without nodal disease is more commonly seen in recurrent disease than at presentation (6).
The most common feature of primary pulmonary Hodgkin disease is a direct extension from hilar nodes toward the lung. A second feature is nodular lesions that are often peripheral with poorly defined borders (Fig 1). The nodules, with or without cavitation, tend to be single or few in number. There is a predilection for the upper lobes in cases of primary pulmonary Hodgkin disease. Radiologic patterns also include a mass (Fig 2) or masslike consolidation and atelectasis of a lobe or segment. This may be due to bronchial compression by the nodes or to endobronchial disease (Fig 3). Bronchoscopy may be used to confirm endobronchial disease. The least common parenchymal manifestation is interstitial infiltration representing disease along the lymphatic routes (6–8,10–15,17–19).
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Figure 1. Nodular sclerosing Hodgkin disease in a 19-year-old woman. The patient had undergone treatment 18 months earlier and was in complete remission. CT scan shows recurrent pulmonary disease with an ill-defined nodular lesion in the right lung (arrow). Mediastinal adenopathy is also seen (arrowheads).
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Figure 2. Nodular sclerosing Hodgkin disease in a 38-year-old man. The patient had undergone treatment 4 years earlier and was in complete remission. CT scan shows bilateral ill-defined lung masses with a nodular lesion in the left lung (arrowhead). There was no mediastinal adenopathy.
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Figure 3a. Nodular sclerosing Hodgkin disease in a 31-year-old man who presented with respiratory symptoms. (a) Anteroposterior chest radiograph shows an ill-defined, right-sided hilar and mediastinal mass. (b) CT scan demonstrates a pulmonary consolidation with an air bronchogram. There is typical micronodulation along the bronchi. The patient underwent bronchoscopy, which demonstrated an endobronchial lesion due to Hodgkin disease.
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Figure 3b. Nodular sclerosing Hodgkin disease in a 31-year-old man who presented with respiratory symptoms. (a) Anteroposterior chest radiograph shows an ill-defined, right-sided hilar and mediastinal mass. (b) CT scan demonstrates a pulmonary consolidation with an air bronchogram. There is typical micronodulation along the bronchi. The patient underwent bronchoscopy, which demonstrated an endobronchial lesion due to Hodgkin disease.
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When these changes are seen in an untreated patient, pulmonary involvement can be diagnosed with confidence. In treated patients, however, biopsy may be needed to differentiate relapse from infection, radiation pneumonitis, or drug-induced lung disease (Fig 4) (10,13).
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Figure 4. Nodular sclerosing Hodgkin disease in a 24-year-old man. CT scan obtained 5 months after institution of C-MOPP-ABVD protocol chemotherapy demonstrates peripheral, ill-defined pulmonary consolidation bilaterally due to bleomycin toxicity.
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Although most parenchymal involvement can be seen at chest radiography, CT is the modality of choice in detecting lung anomalies (6–8,10,13). CT usually shows more extensive parenchymal disease and may therefore change both the stage and the treatment of the disease (Fig 5) (6,13). Moreover, CT is routinely used in patients with lymphoma to assess response to therapy, evaluate recurrence, monitor patients before and after bone marrow transplantation, and diagnose complications such as pneumonia, radiation injury, or secondary tumors (13).
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Figure 5a. Mixed-cellularity Hodgkin disease in a 25-year-old man. The patient had undergone treatment 3 years earlier and was in complete remission. (a, b) Anteroposterior (a) and lateral (b) chest radiographs demonstrate disseminated micronodular disease predominantly involving the left lung. A pulmonary consolidation in the left inferior lobe and a left pleural effusion are also seen. (c) CT scan shows bilateral ill-defined peribronchial micronodular lesions less than 1 cm in diameter. A CT scan obtained 4 cm caudad to c (not shown) showed a shaggy left-sided mass with an air bronchogram, slight consolidation in the right middle lobe, and several peribronchial micronodular lesions.
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Figure 5b. Mixed-cellularity Hodgkin disease in a 25-year-old man. The patient had undergone treatment 3 years earlier and was in complete remission. (a, b) Anteroposterior (a) and lateral (b) chest radiographs demonstrate disseminated micronodular disease predominantly involving the left lung. A pulmonary consolidation in the left inferior lobe and a left pleural effusion are also seen. (c) CT scan shows bilateral ill-defined peribronchial micronodular lesions less than 1 cm in diameter. A CT scan obtained 4 cm caudad to c (not shown) showed a shaggy left-sided mass with an air bronchogram, slight consolidation in the right middle lobe, and several peribronchial micronodular lesions.
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Figure 5c. Mixed-cellularity Hodgkin disease in a 25-year-old man. The patient had undergone treatment 3 years earlier and was in complete remission. (a, b) Anteroposterior (a) and lateral (b) chest radiographs demonstrate disseminated micronodular disease predominantly involving the left lung. A pulmonary consolidation in the left inferior lobe and a left pleural effusion are also seen. (c) CT scan shows bilateral ill-defined peribronchial micronodular lesions less than 1 cm in diameter. A CT scan obtained 4 cm caudad to c (not shown) showed a shaggy left-sided mass with an air bronchogram, slight consolidation in the right middle lobe, and several peribronchial micronodular lesions.
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Pleura
Pleural effusions are not uncommon at presentation (6) and account for about 13% of cases (8). They are not of prognostic significance unless associated with a pleural mass because they rarely contain malignant cells and resolve following treatment (6,8,10). Solid pleural masses, also called pleural-based masses, occur less frequently (Fig 6) and represent an underappreciated site of lymphoma (20). Pleural disease may manifest as plaques, discrete nodules, or a combination of the two. Plaques may occur anywhere along the pleural surface and are frequently accompanied by fluid (6,20). A variety of other diseases can mimic subpleural lymphoma at CT. Thymoma and renal and testicular metastases are particularly confounding because they may demonstrate a combination of mediastinal nodes and pleural-based masses. Pleural lipomas are relatively common and may be diagnosed at CT on the basis of characteristic attenuation values (20).
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Figure 6a. Nodular sclerosing Hodgkin disease in a 26-year-old man. The patient had undergone treatment 3 years earlier and was in complete remission. (a) Anteroposterior chest radiograph demonstrates pleural-based masses in the right apex. There is also a poorly defined left pulmonary consolidation (arrow). (b) CT scan shows a right pleural mass and a left pleural effusion.
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Figure 6b. Nodular sclerosing Hodgkin disease in a 26-year-old man. The patient had undergone treatment 3 years earlier and was in complete remission. (a) Anteroposterior chest radiograph demonstrates pleural-based masses in the right apex. There is also a poorly defined left pulmonary consolidation (arrow). (b) CT scan shows a right pleural mass and a left pleural effusion.
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Heart and Pericardium
Cardiac or pericardial disease apparently results from retrograde lymphatic spread, hematogenous spread, and direct extension from other intrathoracic tumor masses. The prevalence of cardiac involvement by Hodgkin disease at autopsy is estimated at 7.5% (21).
Pericardial effusion may be seen in patients with large mediastinal masses (6,8). It usually resolves in a short time following institution of chemotherapy. Invasion of the pericardium and superior vena cava by a right-sided hilar and mediastinal mass has been reported (6). In addition, a nodular mass in the pericardium has been noted in association with a large pericardial effusion (8).
Thymus
Thymic enlargement is seen in 30%–56% of patients with intrathoracic involvement at presentation (6,8,22). However, Hodgkin disease involving only the thymus is rare (6,23) and may indicate a different disease (24). The clinical significance of thymic involvement in Hodgkin disease is still unclear. With current staging and treatment methods, the thymus is considered to be a "lymph node"; consequently, thymic involvement does not change the stage of the disease (23). The thymic origin of an anterior mediastinal mass in Hodgkin disease can frequently be diagnosed only at follow-up CT (23). The thymus remains enlarged after treatment in about one-third of cases (10). Such posttherapeutic enlargement can be the result of recurrent disease, thymic rebound, or the development or persistence of thymic cysts (6,22–24). The timing of thymic enlargement relative to therapy and the presence of disease elsewhere may permit differentiation between thymic relapse and rebound hyperplasia in most cases. When the diagnosis is uncertain, biopsy should be performed (24).
Distinguishing thymic enlargement is easier with CT than with conventional chest radiography (6,24). The two morphologic criteria that suggest the presence of an enlarged thymus are a triangular configuration of the mass (Fig 7) or the presence of cysts (small areas of slightly reduced attenuation) (Fig 8) (23,24). Parasternal US has been suggested as an alternative technique for the diagnosis of thymic involvement (23) but is of limited value because it does not obviate CT (10,23).
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Figure 7a. Nodular sclerosing Hodgkin disease in a 43-year-old man. (a) CT scan shows the thymus as a triangular prevascular lesion. Right laterotracheal adenopathy is also seen (arrowhead). (b) T1-weighted MR image obtained after administration of gadopentetate dimeglumine shows the thymus with homogeneous enhancement. The thymus appears hyperintense at T2-weighted MR imaging.
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Figure 7b. Nodular sclerosing Hodgkin disease in a 43-year-old man. (a) CT scan shows the thymus as a triangular prevascular lesion. Right laterotracheal adenopathy is also seen (arrowhead). (b) T1-weighted MR image obtained after administration of gadopentetate dimeglumine shows the thymus with homogeneous enhancement. The thymus appears hyperintense at T2-weighted MR imaging.
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Figure 8. Nodular sclerosing Hodgkin disease in a 24-year-old woman. CT scan shows an anterior prevascular mediastinal mass with small areas of low attenuation (arrowheads), findings that are suggestive of thymic involvement. Follow-up CT performed after radiation therapy showed a triangular residual thymic gland.
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Chest Wall
Chest wall involvement is not uncommon and occurs in about 6.4% of cases (8). It may represent either an initial manifestation of the disease or a site of recurrence. If unrecognized, chest wall involvement increases the risk of treatment failure in patients with Hodgkin disease because it changes the stage of the disease and therefore requires more aggressive therapy (9,25). The most common type of chest wall involvement is infiltration of parasternal soft tissues by direct extension from anterior mediastinal nodes, primarily in cases of internal mammary node involvement. Occasionally, masses are seen beneath or between the pectoral muscles without contiguous mediastinal or axillary adenopathy (6,9,25,26). Thoracic spine involvement, when present, is frequently due to direct spread from posterior mediastinal nodes (6,25,26). Most patients with chest wall involvement have associated intrathoracic disease (6,9). However, chest wall masses may occasionally be seen without evidence of intrathoracic disease (6,26).
Castellino et al (8) showed that CT is the modality of choice for detecting chest wall involvement by identifying the disease in 12 of 13 patients with CT alone. More recently, however, it has been shown that MR imaging is more sensitive than CT in this setting (9,25). Short-inversion-time inversion recovery and other fat-saturated sequences are particularly sensitive in detecting chest wall invasion (25).
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Abdomen and Pelvis
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Spleen
The spleen is usually considered to be a "nodal organ" in Hodgkin disease and an extranodal organ in non-Hodgkin lymphoma. However, in this article we present the patterns of splenic involvement for a better understanding of progression in Hodgkin disease. The problem of detecting splenic involvement is still largely unsolved. Staging laparotomy has shown that the spleen is infiltrated in about 30%–40% of patients at presentation (10,27). Splenic involvement is typically diffuse, and only a small minority of cases manifest with nodules larger than 1 cm in diameter (Fig 9). The size of the spleen is not very helpful because diffuse infiltration may be present in spleens of normal size, whereas mild to moderate reactive splenomegaly occurs in about 30% of patients in the absence of lymphoma deposits. Marked splenomegaly almost always indicates infiltration (10,12,28).
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Figure 9. Nodular sclerosing Hodgkin disease in a 29-year-old man. Contrast material-enhanced CT scan shows marked enlargement of the spleen, which contains multiple areas of low attenuation (arrowheads). There are also multiple, slightly hypointense lesions in the liver (solid arrows) and a small lytic bone lesion of the vertebral body (open arrow).
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Nodules are characteristically hypoechoic at US; at CT, they demonstrate low attenuation with reduced contrast material enhancement compared with normal splenic tissue (10,12,27). US may not allow detection of very small deposits, and care must be exercised in interpreting CT scans obtained during the early phase of a bolus injection of contrast material, when the spleen may demonstrate inhomogeneous enhancement that mimics tumor infiltration (27). Detection of splenic lymphoma at MR imaging is not reliable because both the normal spleen and lymphomatous tissue may have similar signal intensity (27). Nodules are hypo- or isointense on T1-weighted MR images and hyperintense on T2-weighted images and demonstrate reduced enhancement after administration of gadopentetate dimeglumine compared with normal spleen (10).
Diffuse involvement of the spleen in Hodgkin disease is nonspecific and not detectable at US or CT (10,27,29); in fact, the spleen may be enlarged but not involved or of normal size despite tumor infiltration (27).
Liver
Primary hepatic Hodgkin disease is very rare. However, secondary liver involvement is fairly common and is usually associated with lymph node disease (10,30). Hodgkin disease of the liver is almost invariably associated with disease of the spleen: Only one case of Hodgkin disease of the liver has been reported without splenic involvement. In fact, the more extensive the splenic disease, the greater the likelihood of hepatic involvement (27). Hepatic involvement is seen at presentation in 6%–20% of patients (10,12,28).
Hepatic involvement is usually diffuse, with discrete nodular lesions being present in only 10% of cases (10,27,30). A combination of the two occurs in less than 3% of patients (30). The small number of positive findings relative to the large number of studies reviewed suggests that gross disease must be present before a pathologic condition can be detected at imaging (30). Indeed, Hodgkin disease manifests more often as miliary lesions (<1 cm in diameter) (Fig 10) than as masses (12,28). The diffuse or infiltrative form of the disease results in patchy, irregular infiltrates originating primarily in the portal areas.
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Figure 10a. Nodular sclerosing Hodgkin disease in a 27-year-old woman. The patient had undergone treatment 2 years earlier and was in complete remission. (a) US image shows hypoechoic nodular infiltration of the liver with involvement of the right kidney (arrowheads). (b) CT scan shows multiple low-attenuation lesions within the liver and spleen.
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Figure 10b. Nodular sclerosing Hodgkin disease in a 27-year-old woman. The patient had undergone treatment 2 years earlier and was in complete remission. (a) US image shows hypoechoic nodular infiltration of the liver with involvement of the right kidney (arrowheads). (b) CT scan shows multiple low-attenuation lesions within the liver and spleen.
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Nodular liver disease has the same characteristics as splenic disease at US, CT, and MR imaging (10). Despite advances in imaging techniques, the sensitivity of US and CT in the detection of hepatic disease remains low (29). Nevertheless, CT is currently the preferred modality for evaluating lymphoma of the liver, with increased sensitivity resulting from the use of dynamic liver scanning and state-of-the-art high-resolution CT scanners (27).
Pancreas
Pancreatic Hodgkin disease is extremely rare and, in almost all cases, secondary to contiguous lymph node disease. Because the pancreas has no definable capsule, it may be difficult to distinguish adjacent lymph node disease from intrinsic pancreatic infiltration (27).
Gastrointestinal Tract
Hodgkin disease rarely involves the gastrointestinal tract (10,28). Primary Hodgkin disease of the gastrointestinal tract usually involves a single site. Multiple sites are rarely involved in disseminated Hodgkin disease. Patients with digestive Hodgkin disease have a poorer 5-year survival rate than those with other forms of the disease (31).
Primary Hodgkin disease of the esophagus seems to be extremely rare, especially in its isolated form (31–34). Most cases of esophageal involvement are secondary (34) and arise by extension from mediastinal lymph nodes (33). Radiologic features at barium examination are always nonspecific, especially in the early stages. A nodular aspect or irregular narrowing of the esophagus due to submucosal tumors represents the main radiologic pattern (34). An unusual case of Hodgkin disease in a patient with acquired immunodeficiency syndrome who presented with esophageal perforation was recently reported (33). Endoscopic US is useful in evaluation, staging, and follow-up (32).
The stomach is the most frequent site of malignant lymphoma of the gastrointestinal tract. Gastric Hodgkin disease accounts for about 9% of all gastric lymphomas (31,35). However, primary gastric Hodgkin disease is extremely rare (35). The radiologic appearances of gastric lymphomas generally reflect the gross pathologic findings. The infiltrating form is the most common (Fig 11) and may be difficult to differentiate from scirrhous carcinoma, particularly when Hodgkin disease with its associated fibrosis is involved (31). CT has proved particularly valuable in diagnosing gastric lymphoma, which demonstrates gastric wall thickening with a smoothly lobulated outer border (31).
Involvement of the small intestine in Hodgkin disease may be associated with a spruelike syndrome. Lymphomas associated with steatorrhea have a higher proportion of Hodgkin disease involvement, and the tumors are often multiple (31). A case of Hodgkin disease with intestinal perforation due to gut involvement was recently reported (36). Hodgkin disease of the colon is uncommon (31).
Genitourinary System
Intrinsic involvement of genitourinary organ systems at presentation is rare (28).
Renal involvement is extremely rare, Hodgkin disease being rather perirenal. Indeed, its radiologic appearance often consists of invasion of the perirenal space by Hodgkin disease without renal parenchymal involvement. CT (versus urography or US) is the diagnostic modality of choice for detecting renal or perirenal masses (37).
Ureteral involvement is extremely rare. Only one case of Hodgkin disease with a ureteral origin has been reported (38). This was a peculiar case involving a single growth in a ureteral situs that manifested early compared with the systemic disease. Urography and CT displayed nonspecific thickening of the ureteral wall that could not possibly be distinguished from involvement caused by urothelial heteroplastic lesions, metastasis via blood or lymph, distant tumors, or isolated non-Hodgkin lymphomas (38).
Bladder involvement is also extremely rare. The only two reported cases involved a nonspecific filling defect arising from the bladder wall (39).
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Skeletal System
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Although presenting symptoms due to osseous involvement rarely occur in Hodgkin disease (40), osseous involvement is seen at radiography in approximately 20% of affected patients during the course of the disease. The poorer the prognosis on the basis of histologic findings, the higher the prevalence of bone destruction during the clinical course (41).
Bone Marrow
Bone marrow involvement is rare at presentation; consequently, marrow biopsy is not systematically indicated as part of initial staging. During the course of illness, 5%–32% of patients will develop bone marrow involvement (42,43). When tumor infiltration is seen at imaging, clinical stage IV disease is presumed (42). Hodgkin disease is more likely to form focal lesions distant from the crests (44).
MR imaging may be more sensitive than all other current imaging modalities in demonstrating bone marrow infiltration and may be superior to blind bone marrow biopsy in detecting early disease (40,41,43,45). It may also be helpful in guiding biopsy (40,42,45). In such cases, a short-inversion-time inversion recovery sequence may be used to generate images on which even small lesions are highly conspicuous (44). A recent study demonstrated that patients with positive MR imaging findings had a higher relapse rate in the 24-month follow-up period than did patients with negative findings (43). Because of the often focal nature of bone marrow involvement, MR imaging and crest marrow sampling are complementary studies for improved marrow staging (44).
Bone
Osseous involvement occurs in 5%–20% of patients during the course of Hodgkin disease but is seen in only 1%–4% at presentation (10,40,41,46–48). Osseous involvement is indicative of widespread, aggressive disease with a poor prognosis (40,46) because it is usually associated with the most unfavorable histologic subtypes (46).
Primary bone Hodgkin disease probably does not exist. Osseous involvement may result from either contiguous spread or a hematogenic process that is usually a late manifestation (10,40,47). The bone lesions are found in the following locations (in decreasing order of frequency): dorsolumbar spine (Fig 12), pelvis (Fig 13), ribs (Fig 14), femora, and sternum. Limb and cervical involvement are rare (40,47–49). Focal extension from adjacent lymph nodes does not alter staging (10).
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Figure 12a. Nodular sclerosing Hodgkin disease in a 29-year-old man. (a, b) Anteroposterior (a) and lateral (b) radiographs of the thoracic spine demonstrate an anterior collapse of the T9 body. (c) Anteroposterior chest radiograph shows a nodular lesion within the left lung (arrow) as well as a small left pleural effusion.
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Figure 12b. Nodular sclerosing Hodgkin disease in a 29-year-old man. (a, b) Anteroposterior (a) and lateral (b) radiographs of the thoracic spine demonstrate an anterior collapse of the T9 body. (c) Anteroposterior chest radiograph shows a nodular lesion within the left lung (arrow) as well as a small left pleural effusion.
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Figure 12c. Nodular sclerosing Hodgkin disease in a 29-year-old man. (a, b) Anteroposterior (a) and lateral (b) radiographs of the thoracic spine demonstrate an anterior collapse of the T9 body. (c) Anteroposterior chest radiograph shows a nodular lesion within the left lung (arrow) as well as a small left pleural effusion.
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Figure 13a. Mixed-cellularity Hodgkin disease in a 17-year-old boy. (a) CT scan demonstrates a large soft-tissue mass involving the right iliac crest and invading the surrounding muscles. (b) On an unenhanced T1-weighted MR image, the mass appears isointense. (c) On a contrast-enhanced T1-weighted MR image, the mass demonstrates marked enhancement. The lesion appeared hyperintense at proton-density-weighted MR imaging.
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Figure 13b. Mixed-cellularity Hodgkin disease in a 17-year-old boy. (a) CT scan demonstrates a large soft-tissue mass involving the right iliac crest and invading the surrounding muscles. (b) On an unenhanced T1-weighted MR image, the mass appears isointense. (c) On a contrast-enhanced T1-weighted MR image, the mass demonstrates marked enhancement. The lesion appeared hyperintense at proton-density-weighted MR imaging.
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Figure 13c. Mixed-cellularity Hodgkin disease in a 17-year-old boy. (a) CT scan demonstrates a large soft-tissue mass involving the right iliac crest and invading the surrounding muscles. (b) On an unenhanced T1-weighted MR image, the mass appears isointense. (c) On a contrast-enhanced T1-weighted MR image, the mass demonstrates marked enhancement. The lesion appeared hyperintense at proton-density-weighted MR imaging.
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Bone scintigraphy has a sensitivity and accuracy of 95% in detecting osseous involvement but is not routinely indicated because most cases of bone Hodgkin disease are revealed at initial chest radiography and CT (10).
The roentgenographic features of bone Hodgkin disease are nonspecific (40). Lesions may be solitary (33%) or polyostotic (66%) (41,47). The edge is usually wide and ill-defined but may be marked by a sclerotic margin. A periosteal reaction, either lamellated (Fig 15) or with a "sunburst" pattern, may occur with bone destruction. The lesions are predominantly osteolytic with blurred borders (Fig 16) but may rarely be sclerotic or mixed (Fig 17) (40,47,48). Fractures are rarely the first manifestations, although several femoral and rib fractures have been reported (40). Soft-tissue tumors are often seen adjacent to bone lesions (41).
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Figure 15a. Nodular sclerosing Hodgkin disease in a 25-year-old woman. (a) Anteroposterior radiograph shows slight osteosclerosis of the proximal end of the right clavicle associated with lamellated periosteal reaction (arrowheads). (b) CT scan demonstrates an associated soft-tissue mass with anterior mediastinal involvement (arrowheads) as well as the periosteal reaction.
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Figure 15b. Nodular sclerosing Hodgkin disease in a 25-year-old woman. (a) Anteroposterior radiograph shows slight osteosclerosis of the proximal end of the right clavicle associated with lamellated periosteal reaction (arrowheads). (b) CT scan demonstrates an associated soft-tissue mass with anterior mediastinal involvement (arrowheads) as well as the periosteal reaction.
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Figure 16a. Nodular sclerosing Hodgkin disease in a 19-year-old man. (a) Anterior (left) and posterior (right) bone scintigrams demonstrate markedly increased activity in the upper end of the left humerus. (b) Anteroposterior radiograph of the left humerus shows an ill-defined geographic area of bone destruction corresponding to the abnormality seen at scintigraphy.
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Figure 16b. Nodular sclerosing Hodgkin disease in a 19-year-old man. (a) Anterior (left) and posterior (right) bone scintigrams demonstrate markedly increased activity in the upper end of the left humerus. (b) Anteroposterior radiograph of the left humerus shows an ill-defined geographic area of bone destruction corresponding to the abnormality seen at scintigraphy.
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Figure 17a. Nodular sclerosing Hodgkin disease in a 47-year-old man. The patient had undergone treatment 5 years earlier and was in complete remission. (a) Lateral radiograph of the upper left knee demonstrates a large mixed lesion in the proximal tibia. No soft-tissue mass is identified. (b) Axial CT scan obtained at the level of the radiographic abnormality shows increased attenuation in the medullary canal of the affected tibia. There is a slightly hyperattenuating soft-tissue mass around the tibial metaphysis (arrowheads). (c) Anteroposterior T2-weighted MR image shows a large lesion involving the entire proximal end of the tibia. (d) Contrast-enhanced fat-suppressed T1-weighted MR image reveals striking heterogeneous enhancement of the lesion with soft-tissue involvement. The hypointense area within the lesion corresponds to the osteosclerotic aspect. (e) Axial contrast-enhanced non-fat-suppressed T1-weighted MR image better demonstrates the soft-tissue mass.
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Figure 17b. Nodular sclerosing Hodgkin disease in a 47-year-old man. The patient had undergone treatment 5 years earlier and was in complete remission. (a) Lateral radiograph of the upper left knee demonstrates a large mixed lesion in the proximal tibia. No soft-tissue mass is identified. (b) Axial CT scan obtained at the level of the radiographic abnormality shows increased attenuation in the medullary canal of the affected tibia. There is a slightly hyperattenuating soft-tissue mass around the tibial metaphysis (arrowheads). (c) Anteroposterior T2-weighted MR image shows a large lesion involving the entire proximal end of the tibia. (d) Contrast-enhanced fat-suppressed T1-weighted MR image reveals striking heterogeneous enhancement of the lesion with soft-tissue involvement. The hypointense area within the lesion corresponds to the osteosclerotic aspect. (e) Axial contrast-enhanced non-fat-suppressed T1-weighted MR image better demonstrates the soft-tissue mass.
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Figure 17c. Nodular sclerosing Hodgkin disease in a 47-year-old man. The patient had undergone treatment 5 years earlier and was in complete remission. (a) Lateral radiograph of the upper left knee demonstrates a large mixed lesion in the proximal tibia. No soft-tissue mass is identified. (b) Axial CT scan obtained at the level of the radiographic abnormality shows increased attenuation in the medullary canal of the affected tibia. There is a slightly hyperattenuating soft-tissue mass around the tibial metaphysis (arrowheads). (c) Anteroposterior T2-weighted MR image shows a large lesion involving the entire proximal end of the tibia. (d) Contrast-enhanced fat-suppressed T1-weighted MR image reveals striking heterogeneous enhancement of the lesion with soft-tissue involvement. The hypointense area within the lesion corresponds to the osteosclerotic aspect. (e) Axial contrast-enhanced non-fat-suppressed T1-weighted MR image better demonstrates the soft-tissue mass.
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Figure 17d. Nodular sclerosing Hodgkin disease in a 47-year-old man. The patient had undergone treatment 5 years earlier and was in complete remission. (a) Lateral radiograph of the upper left knee demonstrates a large mixed lesion in the proximal tibia. No soft-tissue mass is identified. (b) Axial CT scan obtained at the level of the radiographic abnormality shows increased attenuation in the medullary canal of the affected tibia. There is a slightly hyperattenuating soft-tissue mass around the tibial metaphysis (arrowheads). (c) Anteroposterior T2-weighted MR image shows a large lesion involving the entire proximal end of the tibia. (d) Contrast-enhanced fat-suppressed T1-weighted MR image reveals striking heterogeneous enhancement of the lesion with soft-tissue involvement. The hypointense area within the lesion corresponds to the osteosclerotic aspect. (e) Axial contrast-enhanced non-fat-suppressed T1-weighted MR image better demonstrates the soft-tissue mass.
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Figure 17e. Nodular sclerosing Hodgkin disease in a 47-year-old man. The patient had undergone treatment 5 years earlier and was in complete remission. (a) Lateral radiograph of the upper left knee demonstrates a large mixed lesion in the proximal tibia. No soft-tissue mass is identified. (b) Axial CT scan obtained at the level of the radiographic abnormality shows increased attenuation in the medullary canal of the affected tibia. There is a slightly hyperattenuating soft-tissue mass around the tibial metaphysis (arrowheads). (c) Anteroposterior T2-weighted MR image shows a large lesion involving the entire proximal end of the tibia. (d) Contrast-enhanced fat-suppressed T1-weighted MR image reveals striking heterogeneous enhancement of the lesion with soft-tissue involvement. The hypointense area within the lesion corresponds to the osteosclerotic aspect. (e) Axial contrast-enhanced non-fat-suppressed T1-weighted MR image better demonstrates the soft-tissue mass.
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CT and MR imaging allow superior assessment of bone texture and accurate analysis of tumoral bone invasion. CT may demonstrate bone lesions that are not visible at radiography (40).
A bone mass rarely appears in initial disease stages and most commonly involves the sternum, perhaps due to its superficial location and its proximity to thoracic lymph ducts (40). A sternal mass is generally solitary and develops over a variable time period ranging from several days to several months (40,49). Unlike other skeletal masses, it is often associated with subtypes of Hodgkin disease that have a good prognosis (eg, nodular sclerosing) (46,48,49). The tumor is usually round or oval and of variable size (Fig 18) (40,50).
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Figure 18a. Nodular sclerosing Hodgkin disease in a 24-year-old man. (a) Lateral radiograph demonstrates sternal involvement with an associated soft-tissue mass (arrows). (b) CT scan shows a manubrial lesion invading the anterior mediastinum and a mixed bone lesion of the sternum.
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Figure 18b. Nodular sclerosing Hodgkin disease in a 24-year-old man. (a) Lateral radiograph demonstrates sternal involvement with an associated soft-tissue mass (arrows). (b) CT scan shows a manubrial lesion invading the anterior mediastinum and a mixed bone lesion of the sternum.
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Vertebral lesions occur most frequently in the dorsal and lumbar spine and least frequently in the cervical spine. Osteolysis is the rule, but patchy sclerosis and "ivory vertebrae" (Fig 19) as well as mixed lytic and blastic lesions are frequently seen (41,47). Vertebral collapse is also common (40). Paravertebral soft-tissue masses occur consistently. Gouge defects of the anterior border of the vertebrae are frequently the result of erosion by lymph nodes (41).
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Figure 19. Lymphocyte depletion Hodgkin disease in a 34-year-old woman. Lateral radiograph demonstrates an osteoblastic reaction in the second lumbar vertebra with an "ivory vertebra" pattern.
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Head and Neck
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Extranodal disease manifests clinically in less than 1% of cases. However, findings at nasopharyngeal biopsy are positive in about 20% of all cases, and some authors advocate this procedure as part of routine staging of Hodgkin disease (10).
One case has been reported of a patient with a small focus of recurrent Hodgkin disease in the postnasal space associated with paraneoplastic cerebellar degeneration (51).
Primary thyroid Hodgkin disease is extremely rare, with only a few sporadic cases having been reported. In contrast, secondary involvement occurs in 2% of cases. Hodgkin disease of the thyroid gland occurs predominantly in elderly women. Involvement of only one lobe is common (52).
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Central Nervous System
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Central nervous system involvement by Hodgkin disease is uncommon, and clinical manifestations are extremely rare (53). Involvement of the brain or spinal cord by Hodgkin disease, whether primary or secondary, is generally a late manifestation and constitutes a serious and potentially fatal threat to the patient (54,55). Furthermore, this complication may occur in patients who are apparently in remission (56). Lesions are more frequently intraspinal than intracranial (55).
Brain
Brain involvement by Hodgkin disease is so rare that a space-occupying lesion in the brain of a patient with known Hodgkin disease should prompt a second diagnosis (10,56,57).
The existence of primary cerebral Hodgkin disease is still controversial. Rarely, Hodgkin disease may arise primarily in the dura, in the falx, and exceptionally in the brain parenchyma, which represents an isolated intracerebral manifestation (58). Because of limited immunohistochemical evidence, there is still doubt whether histologic criteria for the diagnosis of Hodgkin disease in published cases were met. Some cases that were originally classified as Hodgkin disease were reclassified as B-cell lymphomas, encephalitis, or reticulum cell sarcomamicroglioma after reevaluation (55,58).
Secondary cerebral Hodgkin disease is an uncommon but well-known complication of systemic Hodgkin disease, occurring in 0.2%–0.5% of all cases in advanced stages (56,58,59). Various reports have suggested several mechanisms of intracranial invol
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Abstract
LEARNING OBJECTIVES FOR TEST...
