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Lymphocytic Interstitial Pneumonia: Thin-Section CT Findings in 22 Patients¹

¹ From the Department of Radiology, Vancouver Hospital and Health Sciences Center and University of British Columbia, 855 W 12th Ave, Vancouver, British Columbia, Canada V5Z 1M9 (T.J., N.L.M.); the Department of Radiology, Osaka University Medical School, Japan (T.J., O.H., H.N.); the Department of Radiology, Mayo Clinic, Rochester, Minn (H.A.P., T.E.H.); the First Department of Internal Medicine, Kumamoto University School of Medicine, Japan (K.I.); and the Department of Radiology, National Kinki Chuo Hospital for Chest Disease, Osaka, Japan (M.A.). Received March 25, 1998; revision requested June 18; final revision received October 23; accepted February 12, 1999. Address reprint requests to N.L.M.

	Abstract

TOP Abstract Introduction MATERIALS AND METHODS RESULTS DISCUSSION References

 
PURPOSE: To assess the thin-section computed tomographic (CT) findings of lymphocytic interstitial pneumonia.

MATERIALS AND METHODS: The study included 22 patients (five men, 17 women; age range, 24–83 years; mean age, 50 years) with biopsy-proved lymphocytic interstitial pneumonia. The CT scans were obtained by using 1–3-mm collimation and reconstructed by using a high-spatial-frequency algorithm.

RESULTS: The predominant abnormalities consisted of areas of ground-glass attenuation and poorly defined centrilobular nodules present in all 22 patients and subpleural small nodules seen in 19 patients. Other common findings included thickening of bronchovascular bundles (n = 19), interlobular septal thickening (n = 18), cystic airspaces (n = 15), and lymph node enlargement (n = 15). Less common findings included large nodules, emphysema, airspace consolidation, bronchiectasis, architectural distortion, honeycombing, and pleural thickening.

CONCLUSION: Lymphocytic interstitial pneumonia is characterized by the presence of ground-glass attenuation, poorly defined centrilobular nodules, and thickening of the interstitium along the lymphatic vessels. Lymph node enlargement is more common than previously recognized; it was seen in 68% of patients.

Index terms: Acquired immunodeficiency syndrome (AIDS), 60.206, 60.2068, 60.2518 • Castleman disease, 60.314, 60.391 • Eye, diseases, 22.696 • Lung, CT, 60.12112, 60.12118 • Pneumonitis, lymphocytic interstitial, 60.795 • Sjögren syndrome, 22.696, 60.795

	Introduction

TOP Abstract Introduction MATERIALS AND METHODS RESULTS DISCUSSION References

 
Lymphocytic interstitial pneumonia is a benign lymphoproliferative disorder characterized by a diffuse and exquisitely interstitial proliferation of small lymphocytes and plasma cells (1). Lymphocytic interstitial pneumonia occurs most commonly in patients who have Sjögren syndrome, autoimmune thyroid disease, acquired immunodeficiency syndrome (AIDS), or Castleman disease (2–8).

The natural history of lymphocytic interstitial pneumonia is highly variable (1,2,9). Some patients recover or have slowly improving or stable respiratory disease following treatment with corticosteroids. Over one-third of reported patients have progressive disease. Lymphoma has supervened in some patients, although it is likely that this group of patients had malignant lymphoma from the outset (10).

The appearance of lymphocytic interstitial pneumonia on chest radiographs has been reported to range from interstitial reticular opacities to nodular opacities (11,12). The computed tomographic (CT) findings of lymphocytic interstitial pneumonia have been described in a small number of isolated cases (6,7,13–15). The aim of this study was to assess the thin-section CT findings in 22 patients who had biopsy-proved lymphocytic interstitial pneumonia.

	MATERIALS AND METHODS

TOP Abstract Introduction MATERIALS AND METHODS RESULTS DISCUSSION References

 
We retrospectively identified 22 patients who had biopsy-proved lymphocytic interstitial pneumonia and had undergone CT examination at one of our five institutions between December 1989 and December 1997. The study group consisted of five men and 17 women, with a mean age of 50 years (age range, 24–83 years).

The diagnosis of lymphocytic interstitial pneumonia was obtained by performing open lung biopsy in 13 patients and transbronchial lung biopsy in nine patients. Transbronchial biopsy was performed in six patients with Sjögren syndrome and three patients with Castleman disease. In all patients, tissue diagnosis was obtained within 2 weeks of the CT scans. Ten patients had Sjögren syndrome, seven had Castleman disease, two had AIDS, and three had no underlying disease. All patients with Castleman disease had multicentric disease and hypergammaglobulinemia.

All patients underwent thin-section CT of the chest. The CT scans consisted of 1–3-mm-collimation sections reconstructed by using a high-spatial-frequency algorithm. The protocols consisted of thin sections obtained at 1-cm (18 patients) or 2-cm (three patients) intervals and five thin sections obtained in addition to contiguous 7–10-mm-collimation (conventional) scans obtained through the chest (one patient). In 14 patients, selected images were targeted to a single lung by using a small field of view (13–20 cm).

The CT scans were obtained with a variety of scanners. These included a model 8800, 9800, or CT HiSpeed Advantage scanner (GE Medical Systems, Milwaukee, Wis); X-Vigor scanner (Toshiba, Tokyo, Japan); Quantex scanner (Yokogawa, Hino, Japan); C 100 scanner (Imatron, San Francisco, Calif); and model 1200SX scanner (Picker International, Highland Heights, Ohio). Nine patients received intravenous injections of contrast medium.

The CT images were reviewed by two observers (T.J., N.L.M), and final decisions on the findings were reached by consensus. The observers assessed the presence, extent, and distribution of areas of ground-glass attenuation, airspace consolidation, parenchymal nodules, interlobular septal thickening, thickening of bronchovascular bundles, and cystic airspaces. The presence, extent, and distribution of associated findings such as emphysema, bronchiectasis, honeycombing, architectural distortion, lymph node enlargement, pleural thickening, and pleural effusion were also assessed. Ground-glass attenuation was defined as an area of hazy increased attenuation without obscuration of underlying vascular markings. Airspace consolidation was considered present when the opacities obscured the underlying vessels. Lymphadenopathy was considered present when the short-axis diameter of the nodes was greater than 1 cm. Because only nine patients received intravenous contrast material, the assessment of lymphadenopathy was limited to the mediastinal lymph nodes.

	RESULTS

TOP Abstract Introduction MATERIALS AND METHODS RESULTS DISCUSSION References

 
CT findings of lymphocytic interstitial pneumonia are summarized in the Table. Areas of ground-glass attenuation were present in all 22 patients (Fig 1). The areas of ground-glass attenuation were bilateral in 21 patients (95%) and unilateral in one patient (5%). The areas of ground-glass attenuation had a diffuse distribution in 14 patients (64%), a patchy random distribution in five patients (23%), and a peripheral distribution in three patients (14%).

View larger version (142K): [in this window] [in a new window]   Figure 1a. Lymphocytic interstitial pneumonia in a 24-year-old woman with multicentric Castleman disease. (a) Thin-section (1-mm-collimation) CT scan obtained at the level of the carina demonstrates diffuse distribution of poorly defined centrilobular nodules (arrows) and areas of ground-glass attenuation and thickening of interlobular septa (arrowheads). (b) Histologic section. (Hematoxylin-eosin stain; original magnification, x40.) (c) Same section as in b but at a higher power magnification. (Hematoxylin-eosin stain; original magnification x100.) b and c show peribronchiolar infiltration with lymphocytes and plasma cells (arrows). This peribronchiolar infiltration accounts for the centrilobular nodules seen in a.

View larger version (137K): [in this window] [in a new window]   Figure 1b. Lymphocytic interstitial pneumonia in a 24-year-old woman with multicentric Castleman disease. (a) Thin-section (1-mm-collimation) CT scan obtained at the level of the carina demonstrates diffuse distribution of poorly defined centrilobular nodules (arrows) and areas of ground-glass attenuation and thickening of interlobular septa (arrowheads). (b) Histologic section. (Hematoxylin-eosin stain; original magnification, x40.) (c) Same section as in b but at a higher power magnification. (Hematoxylin-eosin stain; original magnification x100.) b and c show peribronchiolar infiltration with lymphocytes and plasma cells (arrows). This peribronchiolar infiltration accounts for the centrilobular nodules seen in a.

View larger version (150K): [in this window] [in a new window]   Figure 1c. Lymphocytic interstitial pneumonia in a 24-year-old woman with multicentric Castleman disease. (a) Thin-section (1-mm-collimation) CT scan obtained at the level of the carina demonstrates diffuse distribution of poorly defined centrilobular nodules (arrows) and areas of ground-glass attenuation and thickening of interlobular septa (arrowheads). (b) Histologic section. (Hematoxylin-eosin stain; original magnification, x40.) (c) Same section as in b but at a higher power magnification. (Hematoxylin-eosin stain; original magnification x100.) b and c show peribronchiolar infiltration with lymphocytes and plasma cells (arrows). This peribronchiolar infiltration accounts for the centrilobular nodules seen in a.

View larger version (121K): [in this window] [in a new window]   Figure 2. Lymphocytic interstitial pneumonia in a 32-year-old woman with multicentric Castleman disease. Thin-section (1-mm-collimation) CT scan obtained at the level of the right inferior pulmonary vein demonstrates diffuse distribution of thickened bronchovascular bundles (straight white arrows). Small, poorly defined centrilobular nodules (curved arrows) and subpleural nodules (black arrows) are also found.

View larger version (125K): [in this window] [in a new window]   Figure 3. Lymphocytic interstitial pneumonia in an 83-year-old man with AIDS. Thin-section (1-mm-collimation) CT scan obtained at the level of the aortic arch shows extensive bilateral areas of ground-glass attenuation and small, poorly defined centrilobular nodules (arrows).

View larger version (105K): [in this window] [in a new window]   Figure 4. Lymphocytic interstitial pneumonia in a 76-year-old woman with Sjögren syndrome. Thin-section (1.5-mm-collimation) CT scan demonstrates several thin-walled cystic airspaces (straight arrows) in the right middle and lower lobes. Thickened bronchovascular bundles (curved arrows) are also found.

View larger version (145K): [in this window] [in a new window]   Figure 5a. Lymphocytic interstitial pneumonia in a 44-year-old woman with multicentric Castleman disease. (a) Thin-section (1-mm-collimation) CT scan through the left upper lobe demonstrates numerous thickened interlobular septa (arrows). (b) Stereomicroscopic view of pathologic specimen (original magnification, x2) shows thickened interlobular septa (arrows) and peribronchiolar nodules (arrowheads), which correspond to the centrilobular nodules seen in a. The specimen was inflated and fixed with 10% formaldehyde but not stained. (c) Histologic section demonstrates that the interlobular septal thickening in a and b is due to infiltration by lymphocytes and plasma cells within both interlobular septa (arrows) and adjacent alveolar septa (arrowheads). (Hematoxylin-eosin stain; original magnification x40.)

View larger version (140K): [in this window] [in a new window]   Figure 5b. Lymphocytic interstitial pneumonia in a 44-year-old woman with multicentric Castleman disease. (a) Thin-section (1-mm-collimation) CT scan through the left upper lobe demonstrates numerous thickened interlobular septa (arrows). (b) Stereomicroscopic view of pathologic specimen (original magnification, x2) shows thickened interlobular septa (arrows) and peribronchiolar nodules (arrowheads), which correspond to the centrilobular nodules seen in a. The specimen was inflated and fixed with 10% formaldehyde but not stained. (c) Histologic section demonstrates that the interlobular septal thickening in a and b is due to infiltration by lymphocytes and plasma cells within both interlobular septa (arrows) and adjacent alveolar septa (arrowheads). (Hematoxylin-eosin stain; original magnification x40.)

View larger version (175K): [in this window] [in a new window]   Figure 5c. Lymphocytic interstitial pneumonia in a 44-year-old woman with multicentric Castleman disease. (a) Thin-section (1-mm-collimation) CT scan through the left upper lobe demonstrates numerous thickened interlobular septa (arrows). (b) Stereomicroscopic view of pathologic specimen (original magnification, x2) shows thickened interlobular septa (arrows) and peribronchiolar nodules (arrowheads), which correspond to the centrilobular nodules seen in a. The specimen was inflated and fixed with 10% formaldehyde but not stained. (c) Histologic section demonstrates that the interlobular septal thickening in a and b is due to infiltration by lymphocytes and plasma cells within both interlobular septa (arrows) and adjacent alveolar septa (arrowheads). (Hematoxylin-eosin stain; original magnification x40.)

Lymph node enlargement was found in 15 patients (68%), including both mediastinal and hilar lymphadenopathy in 12 patients, mediastinal lymphadenopathy in two patients, and hilar lymphadenopathy in one patient. In all but one patient, lymph node enlargement was present in multiple nodal stations.

Less common findings included nodules 1–2 cm in diameter (n = 9 [41%]), airspace consolidation (n = 9 [41%]), architectural distortion (n = 8 [36%]), emphysema (n = 5 [23%]), bronchiectasis (n = 4 [18%]), pleural thickening (n = 4 [18%]), and honeycombing (n = 1 [5%]).

	DISCUSSION

TOP Abstract Introduction MATERIALS AND METHODS RESULTS DISCUSSION References

 
Previous reports on lymphocytic interstitial pneumonia have focused primarily on the histologic appearance, with reference to the clinical course and the findings on the chest radiograph (1–6). At histologic examination, lymphocytic interstitial pneumonia is characterized by a diffuse interstitial cellular infiltrate composed of a mixture of mature small lymphocytes and plasma cells that widen the alveolar septa (1–3,10,16). Although the process is diffuse, lymphocytic interstitial pneumonia has a propensity to be most severe in the perilymphatic interstitium, that is, along bronchovascular bundles, interlobular septa, and pleura (17). The appearance of lymphocytic interstitial pneumonia on radiographs is nonspecific and includes interstitial reticular opacities and nodular opacities (11,12). The CT findings reported in a small number of cases included areas of ground-glass attenuation, thin-walled cystic airspaces, focal airspace consolidation, centrilobular or peribronchiolar small nodules, and bronchiectasis (6,7,13–15).

In our study, both ground-glass attenuation and poorly defined centrilobular nodules were present in all 22 patients. The areas of ground-glass attenuation and poorly defined centrilobular nodules were usually bilateral and involved all lung zones. These findings are not surprising, given the distribution of lymphocytic interstitial pneumonia along the alveolar septa and adjacent to small airways and vessels (10,16). The pulmonary lymphatic vessels extend along the centrilobular bronchioles (18). The peribronchiolar distribution accounts for the centrilobular nodules seen at thin-section CT. Thickening of bronchovascular bundles, interlobular septa, and subpleural small nodules was seen in the majority of patients. These findings also correspond to the distribution of lymphatic vessels (18,19).

Cystic airspaces were found in 15 patients in our study. Ichikawa et al (14) correlated thin-section CT findings of two cases of lymphocytic interstitial pneumonia with histologic findings obtained through open lung biopsy. Histologic specimens showed nodular infiltrates of lymphoid cells that were peribronchovascular in distribution. It was postulated that the mechanism of cystic airspace formation is partial airway obstruction caused by the peribronchiolar cellular infiltration. Desai et al (15) described three cases of lymphocytic interstitial pneumonia associated with multiple nodules and thin-walled cystic airspaces.

Lymph node enlargement was present in the majority of patients in the current study. This observation differs from the results of radiography of the chest in previous studies that indicated that lymphadenopathy is uncommon in lymphocytic interstitial pneumonia (20,21). The difference is presumably due to the greater sensitivity of CT in demonstrating mediastinal lymph node enlargement. It should be noted, however, that our study is weighted toward patients who had lymphocytic interstitial pneumonia in association with Sjögren syndrome or Castleman disease. Enlarged nodes were present in all seven patients with Castleman disease but in only five of the 10 patients with Sjögren syndrome and three of the five patients with AIDS or no underlying disease.

Hypersensitivity pneumonitis characteristically contains mixed mononuclear cell infiltrates with numerous small lymphocytes, which may resemble lymphocytic interstitial pneumonia (10,16). The characteristic thin-section CT findings of hypersensitivity pneumonitis consist of areas of ground-glass attenuation and small centrilobular nodules (22,23). Both findings are also typically seen in lymphocytic interstitial pneumonia. However, cystic airspaces, interlobular septal thickening, thickening of bronchovascular bundles, and lymph node enlargement are rarely seen in hypersensitivity pneumonitis (22,23).

Multiple cystic airspaces are typically seen at thin-section CT in patients with pulmonary Langerhans histiocytosis and lymphangioleiomyomatosis (24–26). The characteristic CT findings of Langerhans histiocytosis consist of cystic airspaces and multiple nodules (24,25). The nodules sometimes show a centrilobular distribution. Distinguishing features of lymphocytic interstitial pneumonia from Langerhans histiocytosis include the presence of interlobular septal thickening and lymphadenopathy. The absence of centrilobular nodules in lymphangioleiomyomatosis allows ready distinction of this condition from lymphocytic interstitial pneumonia.

Lymphocytic interstitial pneumonia is seen with increased frequency in patients with AIDS (5). In patients with Pneumocystis carinii pneumonia and AIDS, cystic airspace formation is commonly seen (27,28). P carinii pneumonia may also cause small nodules and extensive areas of ground-glass attenuation. Distinguishing features of lymphocytic interstitial pneumonia include the presence of interlobular septal thickening and lymph node enlargement in patients with lymphocytic interstitial pneumonia. It may be difficult, however, to distinguish patients who have lymphocytic interstitial pneumonia from patients who have P carinii pneumonia, as well as from patients who have other AIDS-related complications such as tuberculosis. Moreover, it may be difficult to distinguish lymphocytic interstitial pneumonia from other lymphoproliferative disorders, particularly in patients with AIDS (7). Further studies are required to determine the value of thin-section CT in distinguishing lymphocytic interstitial pneumonia from other pulmonary disorders seen in nonimmunocompromised and immunocompromised patients.

Our study has several limitations. First, it is a descriptive, retrospective review of findings seen on CT scans obtained at five different institutions, which used different protocols.

Second, because open lung biopsy was performed in only 13 of the 22 patients and because the study was retrospective, it provides limited information about the correlation between the CT and the histologic findings. In particular, although 15 (68%) patients had cystic airspaces, in none of the patients was a cystic airspace included in the biopsy specimen.

Third, although similar to those in the study of Ichikawa et al (14), pathologic specimens in our study demonstrated peribronchovascular nodular infiltrates of lymphoid cells, and we found no definite evidence that these infiltrates resulted in distal air trapping and cystic airspace formation.

Last, the study findings do not allow conclusions to be drawn about the accuracy of thin-section CT in differentiating lymphocytic interstitial pneumonia from other disease entities. This would require a blind comparison of the thin-section CT findings in lymphocytic interstitial pneumonia with the findings in other diseases.

In conclusion, lymphocytic interstitial pneumonia is characterized by the presence of ground-glass attenuation, poorly defined centrilobular nodules, and thickening of perilymphatic interstitium. Lymph node enlargement is more common than previously recognized.

	Footnotes

 
Abbreviation: AIDS = acquired immunodeficiency syndrome

Author contributions: Guarantor of integrity of entire study, T.J.; study concepts and design, T.J., N.L.M.; definition of intellectual content, N.L.M., T.E.H.; literature research, T.J., K.I.; clinical studies, T.J., N.L.M., O.H., H.A.P., T.E.H., K.I., M.A.; data acquisition, T.J., N.L.M., K.I.; data analysis, T.J., N.L.M.; manuscript preparation, T.J., N.L.M.; manuscript editing, N.L.M., H.N.; manuscript review, N.L.M., T.E.H.

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