Marginal Zone B-Cell Lymphoma of Bronchus-Associated Lymphoid Tissue

CHEST

Original Research NEOPLASTIC DISEASE

Marginal Zone B-Cell Lymphoma of Bronchus-Associated Lymphoid Tissue* Imaging Findings in 21 Patients Young A Bae, MD; Kyung Soo Lee, MD; Joungho Han, MD; Young-Hyeh Ko, MD; Byung-Tae Kim, MD; Myung Jin Chung, MD; and Tae Sung Kim, MD

Background: Few articles have been published on imaging findings of marginal zone B-cell lymphoma of bronchus-associated lymphoid tissue (BALT) of the lung. We present CT scan and 18 F-fluorodeoxyglucose (FDG) PET scan findings of the disease. Methods: From March 1995 to February 2007, 21 pretreatment patients (male patients, 9; female patients, 12; age range, 35 to 76 years; mean [ⴞ SD] age, 54 ⴞ 10.4 years) were seen who had pathologic diagnoses of marginal zone B-cell lymphoma of BALT. After CT scans were reviewed searching for specific patterns and distribution of parenchymal lung lesions, patients were classified as having the following four different patterns: (1) single nodular or consolidative; (2) multiple nodular or areas of consolidation; (3) bronchiectasis and bronchiolitis; and (4) diffuse interstitial lung disease (DILD) patterns. In six patients, in whom PET/CT scanning was performed, the pattern and the extent of maximum standardized uptake values (mSUVs) of FDG uptake were described. Results: A single nodular or consolidative pattern was observed in 7 of 21 (33%) patients, multiple nodular or areas of consolidation were observed in 9 patients (43%), bronchiectasis and bronchiolitis were observed in 3 patients (14%), and DILD was observed in 2 patients (10%). On PET scans (n ⴝ 6), lesions showed heterogeneous FDG uptake in five patients and homogeneous uptake in one patient, with mSUVs ranging from 2.2 to 6.3 (mean mSUV, 4.2 ⴞ 1.48). Conclusions: Marginal zone B-cell lymphomas of BALT manifest diverse patterns of lung abnormality on CT scans, but single or multiple nodules or areas of consolidation are the main patterns that occur in a majority (76%) of patients. Most lesions show heterogeneous but identifiable FDG uptake on PET scans. (CHEST 2008; 133:433– 440) Key words: CT scan; lung neoplasms; lymphoma; positron emission tomography Abbreviations: BALT ⫽ bronchus-associated lymphoid tissue; DILD ⫽ diffuse interstitial lung disease; FDG ⫽ fluorodeoxyglucose; HU ⫽ Hounsfield unit; mSUV ⫽ maximum standardized uptake value; PET ⫽ positron emission tomography

lymphoid tissue refers to lymM ucosa-associated phoid tissue located under the epithelia of the

GI, respiratory, and urogenital tracts, and their anlages. Mucosa-associated lymphoid tissue located under respiratory tract epithelia is called bronchusassociated lymphoid tissue (BALT). Marginal zone B-cell lymphoma of BALT, originating from the marginal zone and invading the bronchial epithelial tissue, is characterized histopathologically by a cellular infiltrate of lymphoepithelial cells, with a predominance of smaller cell types. Accurate diagnosis depends on immunohistochemical staining findings.

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BALT lymphomas have been associated with Sjo¨gren syndrome, dysgammaglobulinemia, amyloid deposits, collagen vascular diseases, Helicobacter pylori infection, and AIDS.1,2 Marginal zone B-cell lymphomas of BALT are often incidentally identified on chest radiographs, show indolent growth, and remain localized for a long time. They respond well to local therapy. The 5-year survival rate is ⬎ 80% after complete resection.3–5 Therefore, the differentiation of the lymphoma from other lung diseases is important for patient management. CHEST / 133 / 2 / FEBRUARY, 2008

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The most common CT scan findings of marginal zone B-cell lymphoma of BALT were reported initially as consolidation with air bronchograms caused by a cellular lymphocytic infiltrate expanding the interstitium and compressing the adjacent alveoli.6 However, later reports7,8 have suggested more diverse CT scan findings including airspace consolidation, nodules, ground-glass opacity, and small centrilobular and branching nodules (the so-called tree-in-bud sign). In addition, multiple or bilateral distribution of the lesions is more common than focal distribution. Positron emission tomography (PET) with fluorine 18 F-fluorodeoxyglucose (FDG) is used to evaluate glucose metabolism in lung lesions. Due to increased metabolism, malignant tissues typically demonstrate higher FDG uptake than benign lesions and normal tissues. Because marginal zone B-cell lymphomas of BALT show indolent growth, it is expected that the tumors have little FDG uptake. However, to the best of our knowledge, only a limited number of studies9 –11 examining FDG PET scan findings of the lymphoma have been reported. Thus, the purpose of our study was to present CT and 18F-FDG PET scan findings of marginal zone B-cell lymphoma of BALT of the lung.

Materials and Methods Our institutional review board approved our retrospective study with a waiver of informed consent. Patients Enrollment We reviewed all surgical biopsy files recorded from March 1995 to February 2007, and selected patients with the pathologic diagnoses of marginal zone B-cell lymphoma of BALT. We identified a total of 21 pretreatment patients (9 men and 12 women), with ages ranging from 35 to 76 years (mean [⫾ SD] age, 54 ⫾ 10.4 years). None of these patients had AIDS. Pathologic specimens were obtained by video-assisted thoracoscopic surgery biopsy for seven patients, open-lung biopsy for six patients, surgical tumor resection for six patients, and percutaneous core needle biopsy for two patients. In all patients, histopathologic examination showed dense infiltration of small *From the Departments of Radiology (Drs. Bae, Lee, Chung, and T.S. Kim), Diagnostic Pathology (Drs. Han and Ko), and Nuclear Medicine (Dr. B.T. Kim), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Manuscript received August 4, 2007; revision accepted November 2, 2007. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal. org/misc/reprints.shtml). Correspondence to: Kyung Soo Lee, MD, Department of Radiology, Samsung Medical Center, 50, Ilwon-Dong, Kangnam-Ku, Seoul 135-710, Korea; e-mail: [email protected] DOI: 10.1378/chest.07-1956 434

centrocytoid cells, monocytoid B cells, and some plasma cells with lymphoepithelial lesions. Ancillary studies were performed to ensure the diagnosis of marginal zone B-cell lymphoma of BALT by observing monoclonality in an immunohistochemical study including ␬ and ␭ light chain staining and an IgH gene rearrangement study. The phenotyping of the specimens by use of a monoclonal antibody to CD20 disclosed the presence of neoplastic lymphocytes of B-cell lineage. All 21 patients underwent chest CT scans, and 6 patients underwent integrated PET/CT scanning. The mean interval between pathologic diagnoses and CT scan studies was 35 days (range, 2 to 137 days), whereas the mean interval was 6 days (range, 3 to 7 days) between pathologic diagnoses and PET/CT scan examinations. Demographic Data The presence of cigarette smoking history and the presence of symptoms and signs were assessed. In addition, we also reviewed how these lymphomas were detected. The treatment procedures given for each lymphoma in each patient were recorded. If performed, the follow-up results of surgical removal or chemotherapy were also recorded. CT Image Acquisition Enhanced CT scans were obtained using a helical technique using a single-detector CT scanner (HiSpeed Advantage; GE Medical Systems; Milwaukee, WI) in 10 patients, a 4-detector CT scanner (LightSpeed QX/I; GE Medical Systems) in 3 patients, an 8-detector CT scanner (LightSpeed Ultra; GE Medical Systems) in 7 patients, or a 16-detector CT scanner (LightSpeed16; GE Medical Systems) in 1 patient was used. Scanning was performed from the level of the thoracic inlet to the level of the middle portion of the kidneys. For an enhancement study, 100 mL of contrast medium (Iomeron 300; Bracco; Milan, Italy) was administered by IV injection. Imaging started 20 s after the completion of IV contrast medium injection. In all patients, the scanning parameters were 120 kVp and 170 to 200 mA. For the single-helical CT scanner, a 7-mm collimation, a pitch of 1 and a reconstruction thickness of 7 mm were used for scanning and image reconstruction; for the CT scanners with 4 to 16 slices, a beam width of 10 mm, a beam pitch of 1.375 to 1.5, and a reconstruction thickness of 2.5 to 5.0 mm were used. Additional thin-section CT scans (ie, 1.0-mm section thickness, which was reconstructed with a bone algorithm) were obtained in all patients at 10-mm or 20-mm intervals throughout the thorax. Data were interfaced directly to our picture-archiving and communication system (Pathspeed or Centricity 2.0; GE Medical System Integrated Imaging Solutions; Mount Prospect, IL), which displayed all image data on monitors (four monitors, 1,536 ⫻ 2,048 image matrices, 8-bit viewable gray scale, and 60-foot-lambert luminescence). The monitors were used to view both mediastinal window images (width, 400 Hounsfield units [HU]; level, 20 HU) and lung window images (width, 1,500 HU; level, ⫺700 HU). CT Image Interpretation Two chest radiologists, who were unaware of any clinical information, assessed the CT scan images together; decisions on CT scan findings were reached by consensus. The presence of each parenchymal abnormality pattern in each of six lobes (ie, right upper lobe, right middle lobe, right lower lobe, upper division of left upper lobe, lingular division of left upper lobe, and left lower lobe) was recorded. The assessed patterns of parenOriginal Research

chymal abnormalities included the following: tree-in-bud sign (ie, small centrilobular nodules ⬍ 5 mm in diameter and branching nodular structures); nodule (10 to 30 mm in diameter); consolidation (lobular, segmental, or peribronchial); and bronchiectasis. Lobular consolidation was defined as a consolidative lesion 0.5 to 3.0 cm in size, polygonal in shape, and with a subpleural location. Segmental consolidation was defined as a larger pleurally based lesion with a wedge or truncated-cone appearance rather than lobular consolidation. Peribronchial consolidation was defined as a consolidative lesion distributed along the bronchovascular bundles. Bronchiectasis was regarded as being present when bronchi showed dilatation and wall thickening. In addition, the presence of mediastinal or hilar lymph node enlargement and pleural effusion or thickening was recorded. The laterality (unilateral or bilateral) and the locations of the lung lesions were also analyzed. Each lung lobe was evaluated with regard to the presence or absence of each parenchymal abnormality. The predominant distribution of lung abnormalities was classified on the transverse plane into central (ie, central one third), peripheral (ie, peripheral one third), or random, and on the longitudinal plane into upper (ie, higher than hilum), lower (ie, lower than hilum), or random.

After analyzing the pattern and distribution of the parenchymal abnormalities on the CT scan, diseases were classified into the following four patterns: single nodular or consolidative; multiple nodular or areas of consolidation; bronchiectasis and bronchiolitis; and diffuse interstitial lung disease (DILD) patterns. The single-nodular or consolidative pattern was defined when the lesion was composed of a single nodule or a single area of consolidation (Fig 1). The multiple nodular or areas of consolidation pattern was defined when the lung parenchymal abnormalities, either nodular or consolidative lesions, consisted of unilateral or bilateral multiple lung lesions that were distributed along the bronchovascular bundles or along the subpleural lungs (Fig 2). The bronchiectasis and bronchiolitis pattern was defined when lung abnormalities were composed of unilateral or bilateral tree-in-bud patterns of abnormalities with bronchiectasis (Fig 3). The DILD pattern was defined when the lung lesions were composed of patchy areas of ground-glass opacity distributed in the subpleural lungs with lower lung zone predominance (Fig 4). Because serial CT scans were available in 14 patients (follow-up range, 1 to 42 months; mean follow-up time, 9.5 months), interval changes for lung parenchymal abnormalities in

Figure 1. Marginal zone B-cell lymphoma of BALT in a 60-year-old man (patient No. 14 in Table 1). Top left: transverse mediastinal-window CT scan (5-mm section thickness) obtained at the level of the right middle lobar bronchus shows consolidation containing air bronchograms in the lateral segment of right middle lobe. Top right: transverse PET scan obtained at a similar level to that in the top left panel demonstrates high FDG uptake (arrow; mSUV, 6.3) within the lesion. Bottom left: gross pathologic specimen shows parenchymal consolidation (arrows) containing dilated bronchi (arrowheads). Bottom right: low-magnification photomicrograph (hematoxylin-eosin, original ⫻12) reveals a dense cuff of lymphoid cells along blood vessels (arrows). Away from the vessels, lymphoid cells spread into the interlobular septa (arrowheads). www.chestjournal.org

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a standardized protocol using the following settings: 140 kV; 80 mA; tube rotation time, 0.5 s per rotation; pitch, 6; and 5-mm section thickness (to match the PET scan section thickness). Immediately after unenhanced CT scanning, emission PET scanning was performed in the identical transverse field of view. The CT scan data were resized from a 512 ⫻ 512 matrix to a 128 ⫻ 128 matrix to match the PET scan data, so that scans could be fused and CT scan-based transmission maps generated. PET scan data sets were reconstructed iteratively using an ordered subset-expectation maximization algorithm with segmented attenuation correction (two iterations, 28 subsets) using CT scan data. Image Interpretation of PET Scan or the PET Component of PET/CT Scan PET/CT scanning, which was performed in six patients in whom parenchymal abnormalities seen on CT scans were a single nodular or consolidative pattern (n ⫽ 2) or multiple nodular or areas of consolidation (n ⫽ 4), was interpreted by one nuclear medicine physician. The maximum standardized uptake values (mSUVs) of parenchymal lesions were recorded. Patterns of uptake were described as being heterogeneous or homogeneous. Heterogeneous uptake was defined to be present when lung lesions showed spotted or mottled FDG uptake, and homogeneous uptake was defined to be present when the entire tumor showed homogeneous uptake, irrespective of the presence of a tumor necrotic area (ie, an uptake void area). The presence of metastatic lymph nodes, pleural or pericardial seeding, and distant metastasis, if any, were also recorded with the measurement of their mSUVs.

Results Demographic Findings

Figure 2. Marginal zone B-cell lymphoma of BALT in a 52-year-old woman (patient No. 7 in Table 1). Transverse lungwindow CT scans (5-mm-section thickness) obtained at levels of the left innominate vein (top) and bronchus intermedius (middle) show multiple poorly marginated nodules in both upper lobes. Nodules are distributed along the bronchovascular bundle (arrow in the middle panel) or along the pleura or fissure (arrowheads in top panel). Bottom: transverse PET scan obtained at a similar level to that in the middle panel demonstrates increased but with somewhat heterogeneous FDG uptake (arrow; mSUV, 5.2) within the lesion. The mSUV of the right upper lobe lesion (not shown here) was 4.9.

terms of their extent were investigated. In addition, the fates of patients were assessed during the follow-up period. Integrated PET or PET/CT Scan Acquisition PET/CT imaging techniques have been described previously.12,13 Briefly, patients fasted for at least 6 h before the PET/CT scan examination. After ensuring that the peripheral blood glucose level is ⱕ150 mg/dL, patients received an IV injection of 370 MBq (10 mCi) of FDG approximately 45 min before scanning. Scans were acquired using a PET/CT scan device (Discovery LS; GE Medical Systems). CT scanning was performed according to 436

Three patients had associated conditions, as follows: two patients, Sjo¨gren syndrome; one patient, systemic lupus erythematosus. Four men were smokers (mean smoking history, 27 pack-years; range, 20 to 35 pack-years), and the remaining 17 men were nonsmokers. Nine patients had respiratory symptoms (cough, seven patients; dyspnea, four patients). In 12 asymptomatic patients, lung abnormalities were detected incidentally. For these patients, a chest CT scan was performed for the following other reasons: as preoperative lung evaluation, four patients; for an evaluation of hoarseness or facial edema, two patients; for a lung cancer-screening study, six patients. A percutaneous needle biopsy, which was performed in 10 patients, showed positive results for a tumor in only 2 patients (20%; in which a core biopsy was performed). Seven of 21 patients with localized disease underwent surgical resection; one of these 7 patients had recurrent disease that was seen over the follow-up period of 30 months. Ten patients received chemotherapy; 5 patients showed stable disease (mean follow-up period, 17 months), 3 patients showed slight improvement (mean follow-up period, 50 months), and the remaining 2 patients showed slight Original Research

Figure 3. Marginal zone B-cell lymphoma of BALT in a 43-year-old woman with Sjögren syndrome (patient No. 19 in Table 1). Transverse lung-window CT scans (1-mm section thickness) obtained at levels of the right upper lobar bronchus (top left) and inferior pulmonary veins (top right), respectively, show bronchiectasis and centrilobular nodules (arrows in top left panel) and branching structures (so-called tree-in-bud sign; arrows in top right panel) in the right upper and middle lobes. Bottom left: low-magnification photomicrograph (hematoxylin-eosin, original ⫻40) demonstrates peribronchiolar monomorphous lymphoid cell infiltration (arrows). Inset: positive staining for CD20, confirming B-cell lineage of neoplastic cells (original ⫻100). Bottom right: immunohistochemical staining (original ⫻100) for identifying ␬ (left) and ␭ (right) light chain expression demonstrates preferential positive staining in the ␬ light chain, confirming the monoclonality of the B cell. IgH gene rearrangement study (not shown here) also revealed monoclonality.

progression (mean follow-up period, 56 months). Three patients, who were observed without any specific treatment, had stable disease (follow-up period, 14 months). One patient was lost to follow-up (Table 1). CT Scan Findings On serial CT scan studies (follow-up range, 1 to 42 months; mean follow-up time, 9.5 months), which were available in 14 patients (single nodular or consolidative pattern, 3 patients; multiple nodular or areas of consolidation, 7 patients; bronchiectasis and bronchiolitis, 3 patients; DILD pattern, 1 patient) prior to a histopathologic examination, lung parenchymal lesions showed an increase in extent in one patient (over a follow-up period of 42 months, a single consolidation pattern), and no change in the remaining 13 patients. www.chestjournal.org

Lung lesions were unilateral in 12 patients (57%) and bilateral in 9 patients (43%). Consolidation was the most frequent pattern of parenchymal lesions observed in 11 of 21 patients (52%), followed by nodules (8 patients; 38%), ground-glass opacity (8 patients; 38%), tree-in-bud sign (4 patients; 19%), bronchiectasis (3 patients; 14%), and reticulation (2 patients; 10%) [Table 2]. Most parenchymal abnormalities had a random distribution. A single nodular or consolidative pattern (Fig 1) was seen in 7 of 21 patients (33%), multiple nodular or areas of consolidation (Fig 2) in 9 patients (43%), bronchiectasis and bronchiolitis (Fig 3) in 3 patients (14%), and a DILD pattern (Fig 4) in 2 patients (10%) [Table 1]. Cystic lung lesions were observed in three patients (14%) [multiple nodular or areas of consolidation pattern, two patients; DILD pattern, one patient]. CHEST / 133 / 2 / FEBRUARY, 2008

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uptake in one patient (the patient who had a single consolidative lesion in the right middle lobe) [Fig 1]. The extent of FDG uptake was variable, ranging in mSUVs from 2.2 to 6.3 (mean, 4.2 ⫾ 1.48). None of patients had prominent FDG uptake in mediastinal or hilar lymph nodes or in extrathoracic organs.

Discussion

Figure 4. Marginal zone B-cell lymphoma of BALT in a 49-year-old woman with systemic lupus erythematosus (patient No. 20 in Table 1). Transverse lung-window CT scans (1-mm section thickness) obtained at levels of the great vessels (top) and bronchus intermedius (middle) show patchy areas (arrows) of ground-glass opacity and cystic lung lesions (arrowheads) in both lungs. Bottom: low-magnification photomicrograph (hematoxylineosin, original ⫻40) demonstrates lymphocytic infiltration into the peribronchiolar interstitium and alveolar walls (lymphoepithelial lesion; arrows). Also note the cystic lesion (arrowhead). Inset: small lymphoepithelial cells in the bronchiolar mucosa (hematoxylin-eosin, original ⫻100).

In one patient (with bronchiectasis and bronchiolitis pattern), bilateral hilar and mediastinal lymph node enlargement was noticed. In this particular patient, lymph node biopsy disclosed sarcoid-like reaction. Unilateral pleural effusion, which proved to be reactive in nature, was identified in ipsilateral hemithorax in two patients. PET Scan Findings On PET scans, lesions showed heterogeneous FDG uptake in five patients and homogeneous 438

According to a study7 describing 10 cases of marginal zone B-cell lymphoma of BALT, the main patterns of lung lesions seen on CT scans were airspace consolidation or nodules containing air bronchograms within the lesions. In this study, the lesions were multiple in seven cases (70%) and bilateral in six cases (60%). In our study, a multiplicity of lesions was observed in 14 patients (70%), and bilateral disease was observed in 9 patients (43%). Moreover, in our study, CT scan findings were more diverse. Thus, we could classify the pattern of parenchymal lesions into the following four different patterns: (1) single-nodular or consolidative (33%; 7 of 21 patients); (2) multiple nodular or areas of consolidation (43%; 9 patients); (3) bronchiectasis and bronchiolitis (14%; 3 patients); and (4) DILD (10%; 2 patients). The bronchiectasis and bronchiolitis pattern has already been described in a published study,8 but the DILD pattern has not yet been described. Another important finding is the indolent nature of the lesions. For the 14 patients who had undergone serial CT scan studies, most lesions showed no change in their extent over the follow-up period of 9.5 months. Therefore, when persistent parenchymal lesions are observed, we should consider marginal zone B-cell lymphomas of BALT as a possible diagnostic choice. A few studies9,10 have reported that extranodal marginal zone B-cell lymphomas do not show noticeable FDG uptake on PET scans. However, in these studies, the primary tumor sites of the extranodal marginal zone B-cell lymphomas were mostly the stomach, parotid glands, and the lachrymal glands. Only three cases of lung marginal zone B-cell lymphomas were included. In our study, the extent of FDG uptake in marginal zone B-cell lymphomas of BALT seen on PET scans was variable. The mSUVs of the lung lesions ranged from 2.2 to 6.3 (mean mSUV, 4.2). In addition, in five of the six patients in whom PET/CT scanning was performed, most lung lesions showed heterogeneous FDG uptake. The relatively low level of heterogeneous FDG uptake suggests that the parenchymal lesions are metabolically stable. In a study by Beal et al,11 in which PET scans from 11 patients with lung marginal zone Original Research

Table 1—Summary of Demographic Findings of 21 Patients With Marginal Zone B-Cell Lymphoma of BALT* Patient No.

Age, yr/Sex

CT Scan Patterns

Respiratory Symptoms

Diagnostic Methods

Tx Methods

Responses/ Recurrence

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16† 17 18 19† 20‡ 21

45/F 60/F 62/M 63/F 51/F 46/F 52/F 62/M 47/M 51/M 58/F 65/F 35/M 60/M 67/M 76/F 63/F 37/M 43/F 49/F 51/M

Multiple nodular or areas of consolidation Multiple nodular or areas of consolidation Multiple nodular or areas of consolidation Multiple nodular or areas of consolidation Multiple nodular or areas of consolidation Multiple nodular or areas of consolidation Multiple nodular or areas of consolidation Multiple nodular or areas of consolidation Multiple nodular or areas of consolidation Single nodular or consolidative Single nodular or consolidative Single nodular or consolidative Single nodular or consolidative Single nodular or consolidative Single nodular or consolidative Single nodular or consolidative BEBR BEBR BEBR DILD DILD

No Cough No No No Cough No No Cough No No No No Cough Dyspnea Dyspnea Dyspnea/cough No No Dyspnea/cough Cough

OLBx OLBx PCNB OLBx Lobectomy Pneumonectomy OLBx VATS Bx OLBx Lobectomy VATS Bx Lobectomy Lobectomy Lobectomy VATS Bx PCNB OLBx VATS Bx VATS Bx VATS Bx VATS Bx

Chemotherapy Chemotherapy Chemotherapy Observation Surgical resection Surgical resection Chemotherapy Chemotherapy Observation Surgical resection Follow-up loss Surgical resection Surgical resection Surgical resection Chemotherapy Surgical resection Chemotherapy Chemotherapy Chemotherapy Chemotherapy Observation

Improvement Progression Stable Stable No recurrence No recurrence Stable Improvement Stable No recurrence NA No recurrence No recurrence Recurrence Stable No recurrence Improvement Progression Stable Stable Stable

*BEBR ⫽ bronchiectasis and bronchiolitis; OLBx ⫽ open-lung biopsy; VATS Bx ⫽ video-assisted thoracoscopic surgery biopsy; PCNB ⫽ percutaneous core needle biopsy; Tx ⫽ treatment; NA ⫽ not applicable; F ⫽ female; M ⫽ male. †Sjögren syndrome. ‡Systemic lupus erythematosus.

B-cell lymphoma were evaluated, all lesions showed identifiable FDG uptake with mSUVs ranging from 2.6 to 26 (mean mSUV, 6.8; median mSUV, 3.7). Furthermore, most tumors showed identifiable and demonstrable but not avid FDG uptake, as seen in our study. We observed that percutaneous needle biopsy produced a 20% (2 of 10 attempts) diagnostic yield on pathology. We think biopsy specimens obtained by using percutaneous fine-needle aspiration biopsy technique is not adequate enough to yield a pathologic diagnosis of marginal zone B-cell lymphoma of BALT. Therefore, core biopsy specimens, at least, are needed to make a diagnosis of the disease.

The differential diagnosis of marginal zone B-cell lymphoma should include organizing pneumonia/fibrosis, bronchioloalveolar carcinoma, benign spectrum of lymphoproliferative diseases (nodular lymphoid hyperplasia and lymphoid interstitial pneumonia), sarcoidosis, angiitis and granulomatous disease, including Wegener granulomatosis, lymphomatoid granulomatosis, and cryptogenic organizing pneumonia. An indolent nature, multiplicity, bilaterality, and diverse patterns of parenchymal abnormality favor a diagnosis of marginal zone B-cell lymphoma of BALT. However, as lung lesions are indolent, especially in marginal zone B-cell lymphoma of BALT, lymphoid interstitial pneumonia, and organizing pneumonia/fibrosis after pneumonia, an

Table 2—CT Scan Findings in 21 Patients With Marginal Zone B-Cell Lymphoma of BALT* Distribution Lesions, No Patterns Consolidation (n ⫽ 11, 52%) Nodules (n ⫽ 8, 38%) GGO (n ⫽ 8, 38%) TIB (n ⫽ 4, 19%) BE (n ⫽ 3, 14%) Reticulation (n ⫽ 2, 10%)

Single Multiple 5 2 2 0 0 0

6 6 6 4 3 2

Laterality

Involved Lobes

Transverse

Uni

Bi

RU

RM

RL

LU

Li

LL

8 4 3 2 1 0

3 4 5 2 2 2

4 5 5 2 2 2

4 2 4 3 3 1

3 1 4 2 2 2

3 4 4 2 1 2

1 1 2 2 2 1

5 5 5 3 2 2

Central Peripheral 0 0 0 0 0 0

1 2 1 0 0 1

Longitudinal R 10 6 7 4 3 1

Upper Lower R 4 2 2 0 0 0

4 1 2 2 2 1

3 5 4 2 1 1

*Uni ⫽ unilateral; Bi ⫽ bilateral; RU ⫽ right upper lobe; RM ⫽ right middle lobe; RL ⫽ right lower lobe; LU ⫽ left upper lobe; Li ⫽ left upper lingular division; LL ⫽ left lower lobe; R ⫽ random; GGO ⫽ ground-glass opacity; TIB ⫽ tree-in-bud sign; BE ⫽ bronchiectasis. www.chestjournal.org

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overlap of radiologic findings among these diseases is expected. Therefore, tissue confirmation using core biopsy or surgical biopsy specimens, sometimes with the help of immunohistochemical staining, may be needed to make the ultimate diagnosis. Our study is limited by the retrospective nature of the study. In addition, although we included 21 cases of marginal zone B-cell lymphoma of BALT of the lung identified in a single institution during a 12-year period, the number of cases included is still small. Moreover, PET/CT scanning was performed in only six patients who had lung disease patterns of single or multiple nodules or areas of consolidation. Further studies with a large number of cases, specifically with PET/CT scan findings, are needed. In conclusion, marginal zone B-cell lymphomas of BALT manifest diverse patterns of lung abnormality at CT scans, but single or multiple nodules or areas of consolidation are the main patterns, and they show heterogeneous but identifiable FDG uptake on PET scans. The persistent and indolent nature of lesions and the multiplicity and bilaterality of consolidative or nodular lesions seen on serial CT scans may help perform a proper diagnosis of marginal zone B-cell lymphoma of BALT. References 1 Teruya-Feldstein J, Temeck BK, Sloas MM, et al. Pulmonary malignant lymphoma of mucosa-associated lymphoid tissue (MALT) arising in a pediatric HIV-positive patients. Am J Surg Pathol 1995; 19:357–363 2 Lazar EB, Whitman GJ, Chew FS. Lymphoma of bronchusassociated lymphoid tissue. AJR Am J Roentgenol 1996; 167:116

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3 Li G, Hansmann ML, Zwingers T, et al. Primary lymphomas of the lung: morphological, immunohistochemical and clinical features. Histopathology 1990; 16:519 –531 4 Ahmed S, Kussick SJ, Siddiqui AK, et al. Bronchial-associated lymphoid tissue lymphoma: a clinical study of a rare disease. Eur J Cancer 2004; 40:1320 –1326 5 Ahmed S, Siddiqui AK, Rai KR. Low-grade B-cell bronchial associated lymphoid tissue (BALT) lymphoma. Cancer Invest 2002; 20:1059 –1068 6 Knisely BL, Mastey LA, Mergo PJ, et al. Pulmonary mucosaassociated lymphoid tissue lymphoma: CT and pathologic findings. AJR Am J Roentgenol 1999; 172:1321–1326 7 Lee DK, Im J-G, Lee KS, et al. B-cell lymphoma of bronchus-associated lymphoid tissue (BALT): CT features in 10 patients. J Comput Assist Tomogr 2000; 24:30 –34 8 Hwang JH, Kim TS, Han J, et al. Primary lymphoma of the lung simulating bronchiolitis: radiologic findings. AJR Am J Roentgenol 1998; 170:220 –221 9 Hoffmann M, Kletter K, Diemling M, et al. Positron emission tomography with fluorine-18-2-fluoro-2-deoxy-D-glucose (F18-FDG) does not visualize extranodal B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT)-type. Ann Oncol 1999; 10:1185–1189 10 Hoffmann M, Kletter K, Becherer A, et al. 18F-Fluorodeoxyglucose positron emission tomography (18F-FDG-PET) for staging and follow-up of marginal zone B-cell lymphoma. Oncology 2003; 64:336 –340 11 Beal KP, Yeung HW, Yahalom J. FDG-PET scanning for detection and staging of extranodal marginal zone lymphomas of the MALT type: a report of 42 cases. Ann Oncol 2005; 16:473– 480 12 Shim SS, Lee KS, Kim BT, et al. Accuracy of integrated PET/CT using fluorodeoxyglucose for the preoperative staging of non-small cell lung cancer: a prospective comparison with standalone CT. Radiology 2005; 236:1011–1019 13 Kim BT, Lee KS, Shim SS, et al. Stage T1 non-small cell lung cancer: preoperative mediastinal nodal staging with integrated FDG PET/CT: a prospective study. Radiology 2006; 241:501–509

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