Immunophenotypic and molecular analysis of a case of lymphocytic interstitial pneumonia

Abstract

A case of lymphocytic interstitial pneumonia was studied immunophenotypically and with molecular methods in order to clarify its lymphocytic clonality. The patient, a 43 year old Japanese female, underwent lobectomy for a suspected malignant lymphoma as no clear diagnosis could be made from the biopsy specimen. An ill-demarcated, yellowish and elastic firm lesion measuring 60 x 35 x 20 mm in size was located in the peripheral part of the middle lobe of the right lung. Histologically, the alveolar, peribronchial-vascular and subpleural interstitia within the lesion were thickened markedly with severe cellular infiltration largely composed of small lymphocytes with germinal centers. lmmunostaining revealed immunoglobulin (lg) kappa and lg lambda-bearing cells to be evenly distributed, suggestive of polyspecificity. Immunoglobulin gene analysis further demonstrated the unrearranged germ-line DNA but no rearranged band. These results strongly indicated a reactive process rather than a neoplastic nature for the lesion.

Lymphoid Interstitial Pneumonia

“…19 This cellular organization, identical to that seen in hyperplastic peripheral lymph nodes, suggests the LIP lung behaves as a giant lymph organ. 19,102 Similar cellular features have also been seen in the salivary glands of patients with Sjö gren syndrome. 26 Reactive lymphoid follicles are seen in both LIP and FBB, and the morphologic distinction is sometimes difficult 62 and often subjective.…”

“…The interstitial lymphoid cells are mainly T cells and polytypic plasma cells, whereas polyclonal B cells are located in peribronchial germinal centers. 1,10,62,102 The cells reside and also proliferate in these respective areas. 19 This cellular organization, identical to that seen in hyperplastic peripheral lymph nodes, suggests the LIP lung behaves as a giant lymph organ.…”

Chronic Epstein-Barr virus infection causing both benign and malignant lymphoproliferative disorders

“…By contrast, our case had documented polyclonal lymphocytic traits confirmed by immunohistochemical analysis of a transbronchial lung biopsy at the time of LIP diagnosis. This evidence excludes the errors reported previously 9) .…”

“…LIP is characterized by a massive interstitial infiltration of lymphoid cells that are histologically benign and polymorphous, but have the potential to become malignant 3 , 8 , 9) . A previous study of four children reported three cases of LIP that preceded B-cell lymphoma 6) and a recent case study reported lowgrade B-cell lymphomas with microscopic foci resembling LIP in adults 3) .…”

Case 14-1998

“…Molecular analysis of other cases of lymphocytic interstitial pneumonitis has shown an absence of rearrangements in genes controlling immunoglobulins. 18 Primary biliary cirrhosis can be accompanied by lymphocytic interstitial pneumonitis 9,12,19 as well as by fibrosing alveolitis, pleural effusions, pulmonary hemorrhage, and pulmonary hypertension. 3,[20][21][22][23] Other diseases associated with lymphocytic interstitial pneumonitis are Sjögren's syndrome, a potpourri of polyclonal and monoclonal lymphoproliferative processes, various gammopathies, myasthenia gravis, collagenvascular diseases, chronic active hepatitis, [12][13][14] and infections with Epstein-Barr virus, 24 human immunodeficiency virus, 25 and human T-cell lymphotropic virus type I.…”