Introduction: The development of diffuse large cell lymphoma (LCL) in a patient with chronic lymphocytic leukemia (CLL) is known as Richter's Syndrome (RS). Since Maurice Richter first described this in 1928, several investigators have attempted to define the clinical features and the relationship between the two malignancies. Many believe the malignancies have a common clonal origin, with the LCL representing a transformation of CLL while others believe the LCL represents a second malignancy arising from an independent clone.
Incidence of Richter's transformation is approximately 3% and may occur even in patients in ongoing complete remission following chemotherapy. The clinical course is rapidly fatal, with median survival of 5 months. Symptomatic disease due to leukemic cell infiltration in the lung is uncommon, but pulmonary leukemic cell infiltrates are found at autopsy in 30-66% of patients who die from leukemia. The involvement may be parenchymal, pleural, peribronchial or endobronchial. Richter's transformation in the lung is however rare, with relatively few reported cases.
Case Presentation: We present a 63 year old man in whom chronic lymphocytic leukemia was diagnosed 7 years ago. He had no symptoms and was considered stable for many years with white blood cell count of 30,000 with 60% lymphocytes. He is a non smoker and had no other medical problems. Three months prior to presenting to our institution, his white blood cell count had increased to 200,000, with accompanying anemia. Chemotherapy with Chlorambucil was initiated. Two months later, he presented to a nearby hospital with fever, non productive cough and shortness of breath. He was treated for pneumonia, on account of his symptoms, and a new right lower lobe infiltrate on the chest roentgenogram. Two weeks after being on appropriate antibiotics, he had profound malaise, persisting fever, dyspnea and worsening oxygenation.
He was transferred to our institution where his initial physical examination was remarkable for fever, bilateral axillary and inguinal adenopathy, mild splenomegaly, diffuse bilateral wheeze and localized crackles in the right lower lung fields. His white blood cell count was 40,000 with 92% lymphocytes and repeat chest roentgenogram revealed fluffy densities in both lung fields, more on the right, most likely representing a pneumonia. He soon needed mechanical ventilation despite broad antibiotic coverage. Blood cultures and sample obtained from bronchoalveolar lavage of the right lower lobe did not yield any organisms. Transbronchial biopsy was non diagnostic and open lung biopsy was obtained because of the strong suspicion for a non infectious pulmonary complication of chronic lymphocytic leukemia. Histologic and immunologic features of the tissue were consistent with large cell malignant lymphoma of high grade B-cell phenotype. Bone marrow smears showed features consistent with CLL and focal areas with large cells. Flow cytometry showed these cells to be large cell malignant lymphoma of the B cell phenotype, with Lambda surface light chain restriction. The features were consistent with CLL undergoing transformation to a high grade Lymphoma (Richter's Transformation).
Discussion: The clinical features associated with RS include systemic symptoms, progressive asymmetric lymphadenopathy, extranodal disease and rapid clinical deterioration. Predisposing factors to its development are yet to be identified, but karyotypic analysis indicate that patients with multiple chromosomal abnormality are more likely to develop RS. Long term immunosuppression from CLL may be the link between the two malignancies. The median interval between onset of CLL and RS is 48 months. Diagnosis requires tissue biopsy. Effective treatment regimen for RS does not yet exist, but chemotherapy is usually directed toward the LCL.
Pulmonary involvement in CLL is well known. This may include lymphocytic infiltrate in the parenchyma, pleura, peribronchial and endobronchial areas. It is presumed that the transformation to LCL may occur at any site where there is leukemic cell infiltrate. In the largest series of reported patients with RS, Robertson et al, referred to pleural and lung involvement in 5 of 39 cases but did not provide details. Endobronchial RS causing post obstructive pneumonia has been reported. Our patient presented primarily with a pulmonary parenchymal disease simulating a pneumonic process leading to acute respiratory failure. Although antemortem diagnosis was made and chemotherapy initiated, he died from gram negative septicemia.
Conclusion: Richter's transformation is very rare with a poor prognosis. There have been very few reported cases, presenting primarily with pulmonary parenchymal disease.
 Richter MN. Generalized reticular cell sarcoma of lymph nodes associated with lymphocytic leukemia. Am J Pathol 1928; 4:285-292
 Giles FJ, O'Brien SM, Keating MJ. CLL in Richter's transformation. Seminars in Oncology, Vol. 25, No 1 (February), 1998: pp 117-125
Faustinus Onyirimba, MD, B. Lahiri, MD, FCCP--Division of Pulmonary Medicine, University of Connecticut, Farmington, CT; Saint Francis Hospital and Medical Center, Hartford, CT
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