pulmonary marginal zone B-cell lymphoma

Digital cases

 HPC:303 : Pulmonary plasmocytic MALT lymphoma / pulmonary plasmocytic marginal zone lymphoma.
 HPC:317 : Pulmonary MALT lymphoma / pulmonary marginal zone B-cell lymphoma.
 JRC:4041 : Pulmonary lymphoma (NOS) - Probable pulmonary MALT lymphoma.

Definition: A type of extranodal marginal zone lymphoma. The neoplastic lymphoid cells characteristically infiltrate the bronchiolar epithelium to form lymphoepithelial lesions.

Etiology

Pulmonary mucosa-associated lymphoid tissue (MALT) is acquired secondary to antigenic stimuli or autoimmune disease, with subsequent progression to lymphoma. Unlike other forms of marginal zone lymphoma, an aetiological infective agent has not yet been identified. Even in cases associated with H. pylori gastritis, PCR does not demonstrate Helicobacter in the lungs.

Epidemiology

Marginal zone lymphoma accounts for less than 0.5% of all lung neoplasms and of all lymphomas, but constitutes 70-90% of all lung lymphomas. It is not uncommon for patients to have extranodal MALT lymphoma at other sites.

Clinical features

Most patients are older adults. Marginal zone lymphoma in young adults is usually associated with immunosuppression. Autoimmune disease and monoclonal gammopathies are common.

Radiology

Lesions are usually peripheral. There may be a solitary nodule, multiple nodules or diffuse bilateral disease: unilateral disease is more common than bilateral. Associated findings are air bronchograms, airway dilatation, a positive angiogram sign and a halo of ground-glass shadowing at lesion margins. Peribronchovascular thickening may also observed, as may hilar or mediastinal lymph node enlargement and pleural effusions or thickening.

Macroscopy

Resembles lymphoma of lymph node. Rarely, there may be cystic degeneration.

Histopathology

The histopathology resembles that of extranodal marginal zone lymphoma at other sites. In most cases, reactive follicles are smaller than those seen in gastric MALT lymphoma. Although the formation of lymphoepithelial lesions is characteristic, they may also be seen in non-neoplastic pulmonary lymphoid infiltrates.

The lymphoid infiltrate often tracks along bronchovascular bundles and interlobular septa, leaving airways intact, and may involve the pleura. Invasion of bronchial cartilage favours malignancy.

Centrally, the lung parenchyma is destroyed and there may be sclerosis: in some cases, the hyalinosis may be a dominant feature.

There may be epithelioid histiocytes, giant cells or granulomata. Giant lamellar bodies may occur. Amyloid deposition may be seen.

A case with massive crystal storing histiocytosis has been reported.

Immunohistochemistry

As for extranodal marginal zone lymphoma at other sites. Light chain restriction is diagnostically very useful, but may be masked by polyclonal reactive follicles and plasma cells.

The neoplastic cells are usually positive for bcl-2 and bcl-10 and show an aberrant phenotype CD20+/CD43+.

CD21, CD23 and CD35 highlight the meshwork of expanded follicles overrun by neoplastic cells.

Anticytokeratins high-light lymphoepithelial lesions.

Differential diagnosis

 Nodular lymphoid hyperplasia (NLH)

• B cells form abundant follicles with preserved mantles and the interfollicular area consists of T-cells and numerous polyclonal plasma cells, with variable fibrosis.
• The bronchial cartilage and pleura are not invaded.
• The follicles are negative for bcl-2.
• Lymphadenopathy and pleural effusion suggest lymphoma, although lymphadenopathy may be seen in NLH4.
• There is a lack of rearrangement of the immunoglobulin heavy chains in NLH4.

 Lymphoid interstitial pneumonia

• It does not destroy the alveolar architecture.

 Follicular bronchiectasis
 If there is prominent hyalinosis: pulmonary hyalinising granuloma or inflammatory pseudotumour.

 Diffuse large B-cell lymphoma (DLBCL)

• Tumours with a predominance of large cells should be designated as diffuse large B-cell lymphoma: often there is evidence of a pre-existing low grade MALT lymphoma.

 Nodular amyloidosis

• These are non-neoplastic inflammatory foci associated with amyloid deposition.
• Marginal zone lymphoma of the lung may produce amyloid.
• Features that favour MALT lymphoma associated with amyloid are lymphatic tracking of the lymphocytic infiltrate, pleural infiltration, sheet-like masses of plasma cell and the presence of reactive follicles, a dominance of B-cells, an aberrant phenotype (CD20+/CD43+) and light chain restrictions.

Management

If resectable, surgery. Otherwise as for lymphoma elsewhere.

Prognosis

MALToma of lung tends to remain localised, conferring a good prognosis and potential for cure.

Spread may occur to lymph nodes, stomach or salivary glands.

Five year survival is 84-94%, 72% at ten years.

A few cases progress to diffuse large B-cell lymphoma (DLBCL).

See also

 MALT lymphomas
 marginal zone B-cell lymphomas (MZBCL)

Links

 http://e-immunohistochemistry.info/web/Marginal_zone_B-cell_lymphoma_of_the_lung.htm

References

 Tumours of the Lung, Pleura, Thymus and Heart. WHO Classification of Tumours. IARC Press 2004.

 Perry L, Florio R, Dewar A, et al. Giant lamellar bodies as a feature of pulmonary low-grade MALT lymphomas. Histopathology 2000; 36:240-4.

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 Begueret H, Vergier B, Parrens M, et al. Primary Lung Small B-Cell Lymphoma versus Lymphoid Hyperplasia: Evaluation of Diagnostic Criteria in 26 Cases. Am J Surg Pathol 2002; 26:76-81.

 Abbondanzo SL, Rush W, Bijwaard KE, et al. Nodular lymphoid hyperplasia of the lung: a clinicopathologic study of 14 cases. Am J Surg Pathol 2000; 24:587-97

 Dacic S, Colby TV,Yousem SA Nodular amyloidoma and primary pulmonary lymphoma with amyloid production: a differential diagnostic problem. Mod Pathol 2000; 13:934-40

 Koss MN, Hochholzer L, Nichols PW, et al. Primary non-Hodgkin’s lymphoma and pseudolymphoma of lung: a study of 161 patients. Hum Pathol 1983; 14:1024-38

 King LJ, Padley SP, Wotherspoon AC, et al. Pulmonary MALT lymphoma: imaging findings in 24 cases. Eur Radiol 2000; 10:1932-8

 Kurtin PJ, Myers JL, Adlakha H, et al. Pathologic and clinical features of primary pulmonary extranodal marginal zone B-cell lymphoma of MALT type. Am J Surg Pathol 2001; 25:997-1008

 Li G, Hansmann ML, Zwingers T, et al. Primary lymphomas of the lung: morphological, immunohistochemical and clinical features. Histopathology 1990; 16:519-31

 Nicholson AG, Wotherspoon AC, Diss TC, et al. Pulmonary B-cell non-Hodgkin’s lymphomas. The value of immunohistochemistry and gene analysis in diagnosis. Histopathology 1995; 26:395-403

 Nicholson AG, Wotherspoon AC, Jones AL, et al. Pulmonary B-cell non-Hodgkin’s lymphoma associated with autoimmune disorders: a clinicopathological review of six cases. Eur Respir J 1996; 9:2022-5

 Ohshima K, Muta H, Kawasaki C, et al. Bcl10 expression, rearrangement and mutation in MALT lymphoma: correlation with expression of nuclear factor-kappaB. Int J Oncol 2001; 19:283-9

 Kojima M, Nakamura S, Ban S, et al. Primary pulmonary low-grade marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type with prominent hyalinosis. A case report. Pathol Res Pract 2002; 198:685-8

 Fairweather PM, Williamson R,Tsikleas G. Pulmonary extranodal marginal zone lymphoma with massive crystal storing histiocytosis. Am J Surg Pathol 2006; 30:262-7