Vnitr Lek 2014, 60(3):225-238

Lymphomatoid granulomatosis - the past and present

Alice Sýkorová^1,*, Vít Campr², Petra Kašparová³, Eva Kočová⁴, David Belada¹, Marek Trněný⁵, Pavel Žák¹

¹ IV. interní hematologická klinika LF UK a FN Hradec Králové, přednosta doc. MUDr. Pavel Žák, Ph.D.

² Ústav patologie a molekulární medicíny 2. LF UK a FN Motol Praha, přednosta prof. MUDr. Roman Kodet, CSc.

³ Fingerlandův ústav patologie LF UK a FN Hradec Králové, přednosta prof. MUDr. Aleš Ryška, Ph.D.

⁴ Radiologická klinika LF UK a FN Hradec Králové, přednosta prof. MUDr. Antonín Krajina, CSc.

⁵ I. interní klinika - klinika hematologie 1. LF UK a VFN Praha, přednosta prof. MUDr. Marek Trněný, CSc.

Background:
Lymphomatoid granulomatosis (LyG) is a rare multisystemic angiocentric and angiodestructive B lymphoproliferative disease that was first described by Liebow in 1972. Disease was then in the "gray zone" between vasculitis and lymphoproliferative disease. LyG is currently categorized as a primary B lymphoproliferative disease associated with Epstein-Barr (EB) virus according to the World Health Organization (WHO) classification of tumours.


Epidemiology, clinical course and treatment:
Lymphomatoid granulomatosis is a rare disease with unknown prevalence. It occurs more often in males (male : female ratio 2 : 1) between the 5^th to 6^th decade of life and is more frequent in Europe than in Asia. Lungs are typically the predominantly affected organ; the disease spreads predominantly by extralymphatic manner. Spleen and lymph nodes are affected at an advanced stage. The clinical features are often nonspecific. Dyspnea, cough, hemoptysis, chest pain are the most common features with/without B symptoms (fever, night sweats, weight loss) in the pulmonary involvement. The radiographic finding of the lung is very diverse, but when there are multiple bilateral nodular lesions with basal predominance in perilymphatic distribution, we should think of this disease, although LyG rarely occurs. The histopathologic examination of affected tissue (most commonly the lung) is necessary to confirm the diagnosis. The thoracoscopy is used mainly. When the pulmonary findings are without any response to antibiotics, the autoimmune cause and other granulomatous inflammations (tuberculosis, sarcoidosis, etc.) are excluded, this diagnostic performance is indicated. Prognosis is variable - from spontaneous remission to progressive disease, often with aggressive behavior. Median survival is 14 months from diagnosis and mortality rate is 60% in the first year - despite the treatment. Treatment strategy is chosen depending on the histological grade. The therapy is not yet standardized. Interferon α, rituximab, glucocorticoids, cyclophosphamide and combined immunochemotherapy have been used for the treatment. The disease may lead to pulmonary failure, fatal CNS (central nervous system) involvement and sometimes develops into progressive EB virus positive lymphoproliferative disorder.

Conclusion:
Improvements in understanding of the biology of LyG, especially in determining the precise role of EB virus infection in its pathogenesis may lead to optimization of treatment strategies for this disease. Novel treatment modalities are urgently needed due to unfavourable prognosis. Adoptive immunotherapy appeals to be a promising approach.

Keywords: epidemiology; Epstein-Barr virus; lymphomatoid granulomatosis

Received: November 6, 2013; Accepted: December 17, 2013; Published: March 1, 2014  Show citation