Lymphomatoid granulomatosis, LYG


An angiocentric, angiodestructive lymphoproliferative disease of extranodal sites composed of EBV-positive B-cells and reactive T-cells5,7.


Angiocentric immunoproliferative lesion.


This is a rare condition, usually presenting in adults9, but also seen in children with immunodeficiency. The male to female ratio is 2:16,9. Predisposing factors include immunodeficiency from various causes; AIDS4,5, allogeneic organ transplantation5, Wiskott-Aldrich syndrome5, and X-linked lymphoproliferative syndrome, treatment for leukaemia or lymphoma, and agnogenic myeloid metaplasia. In idiopathic cases, impairment of various immune parameters has been reported: immunoglobulin concentrations are often abnormal9. There is a case report of LYG after treatment of a GIST with imatinib.


Clinical features

Most commonly involves the lung, with most patients developing pulmonary involvement at some stage. Other common sites are skin (25-50%)1,5, kidney (32%)5, liver (29%)5, brain (26%)5, upper respiratory tract and gastrointestinal tract. Lymph nodes and spleen are rarely involved. Most patients present with respiratory tract signs6,9, fever9, rash9, malaise, weight loss, arthralgias, myalgias and GI symptoms. The upper respiratory tract may show ulcero-destructive lesions.


The pulmonary involvement results in nodules9 of varying size within the mid and lower zones, often of "cannon ball" appearance. Large nodules become centrally necrotic and cavitate.


There is an angiocentric angiodestructive polymorphous lymphoid infiltrate. This is composed of lymphocytes admixed with plasma cells, immunoblasts and histiocytes10. Neutrophils and eosinophils are inconspicuous and well-formed granulomata are absent. The lymphocytes are mainly T-cells, which are negative for EBV3. The EBV-positive B-cells3,4,8,10 resemble immunoblasts or Hodgkin cells; multinucleate forms may be present. However, Reed-Sternberg cells are not seen. The vessel walls are infiltrated by lymphocytes, which may result in infarct-like tissue necrosis. Fibrinoid necrosis of vessel wall is common. Despite the name, granulomas are not a feature. There may be progression to EBV-positive DLBCL.



Skin lesions1 consist of red dermal papules or subcutaneous nodules. The histology mirrors that seen in the lungs. They consist predominantly of CD4+ T-cells. The infiltrate is angiodestructive and necrosis occurs. EBV-positive cells are harder to demonstrate than in the lungs. A few patients have white atrophic plaques in which EBV-positive cells are not demonstrable.







usually positive


variably positive


may be aberrantly expressed by the atypical B-cells4


may be aberrantly expressed by the atypical B-cells4


variably positive


positive in the larger atypical / pleomorphic cells


Using combined immunohistochemistry, the proliferating cells have been shown to be the B-cell component2.

The reactive T-cells are CD3+ and have a cytotoxic phenotype as defined by the expression of CD8 and the cytotoxic granule proteins TIA-1 and granzyme B6.


Differential diagnosis


Grades 1 and 2 may be treated with interferon alpha 2b5,11. Grade three is treated as for DLBCL.


The prognosis is very variable but the median survival is less than two years6. Some cases show waxing and waning disease or spontaneous regression.


World Health Organization Classification of Tumours, Tumours of the haematopoietic and lymphoid tissues, IARC Press 2001.

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

1 Beaty MW, Toro J, Sorbara L, et al. Cutaneous lymphomatoid granulomatosis: correlation of clinical and biologic features. Am J Surg Pathol 2001; 25:1111-20

2 Guinee DG, Jr., Perkins SL, Travis WD, et al. Proliferation and cellular phenotype in lymphomatoid granulomatosis: implications of a higher proliferation index in B cells. Am J Surg Pathol 1998; 22:1093-100

3 Guinee D, Jr., Jaffe E, Kingma D, et al. Pulmonary lymphomatoid granulomatosis. Evidence for a proliferation of Epstein-Barr virus infected B-lymphocytes with a prominent T-cell component and vasculitis. Am J Surg Pathol 1994; 18:753-64

4 Haque AK, Myers JL, Hudnall SD, et al. Pulmonary lymphomatoid granulomatosis in acquired immunodeficiency syndrome: lesions with Epstein-Barr virus infection. Mod Pathol 1998; 11:347-56

5 Jaffe ES,Wilson WH. Lymphomatoid granulomatosis: pathogenesis, pathology and clinical implications. Cancer Surv 1997; 30:233-48

6 Koss MN, Hochholzer L, Langloss JM, et al. Lymphomatoid granulomatosis: a clinicopathologic study of 42 patients. Pathology 1986; 18:283-8

7 Nicholson AG, Wotherspoon AC, Diss TC, et al. Lymphomatoid granulomatosis: evidence that some cases represent Epstein-Barr virus-associated B-cell lymphoma. Histopathology 1996; 29:317-24

8 Myers JL, Kurtin PJ, Katzenstein AL, et al. Lymphomatoid granulomatosis. Evidence of immunophenotypic diversity and relationship to Epstein-Barr virus infection. Am J Surg Pathol 1995; 19:1300-12

9 Pisani RJ,DeRemee RA. Clinical implications of the histopathologic diagnosis of pulmonary lymphomatoid granulomatosis. Mayo Clin Proc 1990; 65:151-63

10 Taniere P, Thivolet-Bejui F, Vitrey D, et al. Lymphomatoid granulomatosis--a report on four cases: evidence for B phenotype of the tumoral cells. Eur Respir J 1998; 12:102-6

11 Wilson WH, Kingma DW, Raffeld M, et al. Association of lymphomatoid granulomatosis with Epstein-Barr viral infection of B lymphocytes and response to interferon-alpha 2b. Blood 1996; 87:4531-7

This page last revised 21.6.2005.

©SMUHT/PW Bishop