Pulmonary B-cell non-Hodgkin's lymphoma of MALT origin

Adult Respiratory Distress Syndrome

Pathologic and clinical features of primary pulmonary extranodal marginal zone B-cell lymphoma of MALT type. Am J Surg Pathol 2001 Aug;25(8):997-1008.

We reviewed pathologic, phenotypic, and clinical features of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) type primarily involving lung to address unresolved questions regarding behavior and pathologic features of unambiguously diagnosed pulmonary MALT lymphoma. Lung specimens from 50 patients were reviewed. Forty-one had low-grade MALT lymphoma. Nine had low-grade MALT lymphoma and diffuse large B-cell lymphoma. The patients included 32 women and 18 men with a median age of 68 years (range 34-88 years). Half of the patients were asymptomatic at the time lymphoma was diagnosed. Radiographic abnormalities were more commonly unilateral (37 patients) than bilateral (12 patients). Localized masses or nodules occurred in 39 patients. Associated autoimmune disorders (29%) and monoclonal gammopathies (43%) were common. Low-grade lymphomas formed intraparenchymal masses composed of centrocyte-like cells, plasmacytoid lymphocytes, and plasma cells that formed lymphoepithelial lesions and exhibited a lymphangitic growth pattern. Mediastinal lymph nodes were involved histologically in 44% of cases. Lymphoma-specific survival was 71.7% at 10 years, and overall survival was significantly worse than age-and gender-matched control patients. None of the following features predicted those patients who had an adverse outcome: systemic symptoms, presence of autoimmune disorders or paraproteinemia, anatomic distribution and number of pulmonary lesions, lymph node involvement, or presence of anthracycline-treated large B-cell lymphoma.

Although the lung is frequently involved by disseminated lymphoma, isolated pulmonary lymphoma is rare, accounting for less than 1% of all extranodal localized disease.

Three broad categories of lymphoma of the lung require recognition: in rare instances, large B cell type lymphoma can present primarily in the lung ; a second variant is by T cell lymphoma presenting as an angiocentric process. However, the most common histologic subtype is represented by low-grade mucosa-associated lymphoid tissue (MALT) lymphoma, often in the past considered as a pseudotumor because of its long indolent natural history.

Visit: Pulmonary Lymphoproliferative Disease ; Lymphocytic Interstitial Pneumonia / Follicular Bronchiolitis

In 1963, Salzstein distinguished pulmonary lymphoma from “pseudolymphoma”. Pseudolymphoma was regarded as a reactive condition similar to pseudolymphomas seen at other sites.

Most cases are now thought to be neoplastic from onset and arise from pulmonary MALT.

Age and sex: Patients present in their fifth to seventh decades. It is slightly more common in male.

Clinical presentation: In low-grade disease, the commonest presentation is an asymptomic mass on routine chest x-ray.

High-grade lymphomas are however, nearly always symptomatic.

Constitutional symptoms include weight loss, fever and night sweats.

Previous or synchronous MALT lymphoma at other extranodal sites may be present.

Etiology: Unlike gastric lymphomas where there is a clinical association with previous Helicobacter pylori infection, there is no consistent clinical association with pulmonary counterparts. Some cases of pulmonary lymphomas have been described in patients with autoimmune disorders, some with fibrosing alveolitis.

Diagnosis: Surgical lung biopsies and resection have been the commonest diagnostic procedures.

Identification of gene rearrangements using the polymerase chain reaction has successfully proven monoclonality in bronchoalveolar lavage fluid and both bronchoscopic and transbronchial biopsies, in situations where previous diagnoses had been classified as equivocal.

Microscopic features: Image1 [The bronchiolar epithelium is infiltrated but is not destroyed] ; Image2 [The infiltrate expands and destroys the interstitium, consists of neoplastic cells (black arrow) which are CD20 positive and reactive CD3 positive T-cell population in the backround (brown arrow).]

Low-grade tumours are composed of centrocyte-like, lymphocyte-like or monocytoid cells. These are all thought to be variations of the same neoplastic cell.

Features of plasmacytoid differentiation are often seen in the smalll lymphocytes, and Russell or Dutcher bodies may be present. A distinguishing feature of the lymphoid cell population is the presence of a rim of clear cytoplasm surrounding the nucleus of the cells, resembling that of centrocytes or monocytoid B-cells.

In resection specimens, and to a lesser extent in open lung biopsies, a characteristic pattern of spread along bronchovascular bundles and interlobular septa is seen.

Subsequent expansion and destruction of the alveolar walls and filling of the alveolar spaces give rise to nodules that coalesce centrally, often with hyaline sclerosis towards their centers.

Reactive follicles with well-formed germinal centers may be seen in 70% of cases

Other features of MALT lymphomas, such as lymphoepothelial lesions, are often seen. Diagram

This pattern of spread is not seen in high-grade tumours, in which the infiltrate is more diffuse and destructive.

Giant lamellar bodies may be rarely noted.

Necrosis is almost always limited to the high-grade tumors.

The neoplastic cells are of B-cell phenotype with a variable reactive T-cell population in the background.

Light chain restriction is observed in 30-70% of cases.

Amplification of the immunoglobulin heavy chain gene with the polymerase chain reaction has shows monoclonality in 60% of low-grade lymphomas, but only occasionally in high-grade disease.

Primary Lung Small B-Cell Lymphoma versus Lymphoid Hyperplasia: Evaluation of Diagnostic Criteria in 26 Cases.Am J Surg Pathol.2002 Jan;26(1):76-81

Primary lung non-Hodgkin's lymphoma is a rare neoplasm mostly represented by low-grade B-cell lymphomas of mucosa-associated lymphoid tissue. Their diagnostic criteria are now well defined on surgical specimens, but pathologists may experience difficulties in distinguishing them on exiguous biopsies from benign lymphoid hyperplasia and other lymphomas. Therefore, we examined a series of 26 lung lymphoid lesions to further define the pathologic features of either lymphoma or lymphoid hyperplasia on small specimens. We observed 16 primary lung non-Hodgkin's lymphomas with a large predominance of low-grade mucosa-associated lymphoid tissue-type lymphomas (87.5%, n = 14). There were no autoimmune disorders, but three patients had a concomitant infectious disease (hepatitis C virus and Helicobacter pylori gastritis). One patient presented with a synchronous pulmonary adenocarcinoma. As well as the classical mucosa-associated lymphoid tissue cellular infiltrate, immunohistochemical characterization of the 14 mucosa-associated lymphoid tissue-type lymphomas revealed the CD20+/CD43+ centrocyte-like cell phenotype in 10 cases (71.5%). Although the lymphoepithelial lesions observed in all lymphomatous cases have been reported in lung lymphoid hyperplasia, the determination of B-cell CD20+/CD43+ phenotype of the intraepithelial lymphocytes highly increased the specificity of lymphoepithelial lesions. A monoclonal immunoglobulin heavy chain gene rearrangement was present in 71.4% of the mucosa-associated lymphoid tissue-type lymphoma specimens. Investigation of H. pylori by polymerase chain reaction detection was negative, even for the two cases associated with H. pylori gastritis.

Primary pulmonary non-Hodgkin's lymphoma. Jpn J Clin Oncol. 2004 Sep;34(9):510-4

BACKGROUND: Primary pulmonary non-Hodgkin's lymphoma is a very rare neoplasm. It is represented most commonly by marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type. Although there have been a few reviews of this lymphoma, clinical features, diagnostic procedure, optimal management and prognostic factors have not been well defined. METHODS: We reviewed the medical records of 24 patients who were pathologically and clinically diagnosed as primary pulmonary lymphoma between September 1995 and June 2003. RESULTS: There were 13 patients with MALT lymphoma and two with MALT lymphoma accompanied by large B-cell lymphoma, seven with diffuse large B-cell lymphoma and two with anaplastic large cell lymphoma. Half the patients were asymptomatic at presentation; 46% had respiratory symptoms and 16.7% had B-symptoms. Initial radiological findings were variable including nodules, masses, infiltrates or consolidation. The majority of patients (66.7%) needed surgical approaches (open thoracotomy or video-assisted thoracoscopy) for definite diagnosis. Bronchoscopy was performed in 83%, but only 30% showed a diagnostic yield. The 13 patients with MALT lymphoma were treated with a variety of modalities such as observation, surgery and single or combination chemotherapy, and combination chemotherapy was administered to 11 patients with non-MALT lymphoma regardless of surgery. The overall survival rate at 3 years for all 24 patients was 86% with a median follow-up of 32 months. CONCLUSION: Although this entity of lymphoma appears to have a good prognosis, further clinical experience and long-term follow-up are needed to identify prognostic factors.