Contributions
Abstract: EP652
Type: E-Poster Presentation
Session title: Chronic lymphocytic leukemia and related disorders - Clinical
Background
Cutaneous infiltration by leukemic cells with clinically identifiable skin lesions, also called leukemia cutis (LC), has seldom been reported in chronic lymphocytic leukemia (CLL). There is no available data on the genetic background of LC-CLL.
Aims
In this study we retrospectively analyzed the clinical, histopathological, and molecular features of 46 CLL patients with specific LC from centers of the FILO.
Methods
We collected clinical and biological data including cytogenetic aberrations assessed by FISH, karyotype, IGHV mutational status and amplicon-based next-generation sequencing of 13 CLL-associated mutated genes from peripheral CLL cells.
Results
We identified 46 cases of skin biopsy-proven LC-CLL. All patients had proven CLL prior to LC. Median time between skin manifestations and CLL was 5.4 years (1-18 years). Skin lesions were either diffuse (n=16), localized (n=13) or regional (n=9). Head and neck were the most common site (22 cases) with a high incidence of earlobe lesions (10/46 cases), while lesions on arms and legs, trunk and extremities were found in 17, 13, and 14 cases respectively. The most common skin manifestations were papulonodular (24/46 cases) and non-infiltrated erythematous lesions (n= 9). Plaques, vesicles, mosquito bite-like, rhinophyma-like, ulcerations or necrotic lesions were uncommon. Some infiltrates appeared at the sites of previous scars following herpes, mosquito bite or a plant wound in 4 patients.
A majority of cases were IGHV mutated (n=21/37, 57%). The IGHV4-34 gene ranked among the most frequent IGHV genes (8/37, 21.6%) as compared to usually 10% of CLL. Conventional karyotype was performed in 25 patients. It was normal in 8 cases (32%) and complex (>3 abnormalities) in 6 cases (25%). An intriguing finding was the unexpected high frequency of t(14;18) translocation in 6/25 patients (25%), while it usually occurs in < 5% of CLL. Among the 34 cases tested by FISH: trisomy 12 was frequent (10/34; 29%), while 13q, 11q and 17p deletions were found in 23%, 12% and 9% respectively. Molecular testing was performed in 38 patients: 13 patients harbored only one mutation (34%) while 11 patients had 2 to 5 mutations. The most frequently mutated genes were NOTCH1/FBXW7 (34%), TP53 (21%), SF3B1 (13%) and BIRC3 (13%).
Follow-up data were obtained for 34 patients. Skin lesions tended to occur in stage A and before any treatment: 20 patients (60%) had skin lesions before the first line of treatment while 14 (40%) had received at least 1 line of treatment before any skin manifestations. Six patients developed skin lesions later in the course of the disease. Thirty-one patients were treated: 13 patients received a fludarabine or bendamustine-based regimen, 5 chlorambucil based, 5 Ibrutinib, 4 polychemotherapy, 1 obinutuzumab, 2 venetoclax and 1 idelalisib. Treatment was initiated because of the presence of skin lesions in 15 patients. Systemic treatment led to a complete skin response in 74% (23/31) of patients. The 8 patients who did not experience a complete skin response (among which the 5 patients treated with chlorambucil) achieved a partial response of the systemic CLL disease as well.
Conclusion
In this large CLL-LC cohort, we did not find a specific clinical or biological profile associated with LC, nor any difference related to morphology or site of skin lesions. t(14;18) is enriched and we are currently investigating its significance in this atypical clinical presentation of CLL. Our results suggest that CLL patients with cutaneous lesions are not associated with poor prognosis features and they respond well to CLL systemic treatment.
Keyword(s): Chronic lymphocytic leukemia, Mutation analysis
Abstract: EP652
Type: E-Poster Presentation
Session title: Chronic lymphocytic leukemia and related disorders - Clinical
Background
Cutaneous infiltration by leukemic cells with clinically identifiable skin lesions, also called leukemia cutis (LC), has seldom been reported in chronic lymphocytic leukemia (CLL). There is no available data on the genetic background of LC-CLL.
Aims
In this study we retrospectively analyzed the clinical, histopathological, and molecular features of 46 CLL patients with specific LC from centers of the FILO.
Methods
We collected clinical and biological data including cytogenetic aberrations assessed by FISH, karyotype, IGHV mutational status and amplicon-based next-generation sequencing of 13 CLL-associated mutated genes from peripheral CLL cells.
Results
We identified 46 cases of skin biopsy-proven LC-CLL. All patients had proven CLL prior to LC. Median time between skin manifestations and CLL was 5.4 years (1-18 years). Skin lesions were either diffuse (n=16), localized (n=13) or regional (n=9). Head and neck were the most common site (22 cases) with a high incidence of earlobe lesions (10/46 cases), while lesions on arms and legs, trunk and extremities were found in 17, 13, and 14 cases respectively. The most common skin manifestations were papulonodular (24/46 cases) and non-infiltrated erythematous lesions (n= 9). Plaques, vesicles, mosquito bite-like, rhinophyma-like, ulcerations or necrotic lesions were uncommon. Some infiltrates appeared at the sites of previous scars following herpes, mosquito bite or a plant wound in 4 patients.
A majority of cases were IGHV mutated (n=21/37, 57%). The IGHV4-34 gene ranked among the most frequent IGHV genes (8/37, 21.6%) as compared to usually 10% of CLL. Conventional karyotype was performed in 25 patients. It was normal in 8 cases (32%) and complex (>3 abnormalities) in 6 cases (25%). An intriguing finding was the unexpected high frequency of t(14;18) translocation in 6/25 patients (25%), while it usually occurs in < 5% of CLL. Among the 34 cases tested by FISH: trisomy 12 was frequent (10/34; 29%), while 13q, 11q and 17p deletions were found in 23%, 12% and 9% respectively. Molecular testing was performed in 38 patients: 13 patients harbored only one mutation (34%) while 11 patients had 2 to 5 mutations. The most frequently mutated genes were NOTCH1/FBXW7 (34%), TP53 (21%), SF3B1 (13%) and BIRC3 (13%).
Follow-up data were obtained for 34 patients. Skin lesions tended to occur in stage A and before any treatment: 20 patients (60%) had skin lesions before the first line of treatment while 14 (40%) had received at least 1 line of treatment before any skin manifestations. Six patients developed skin lesions later in the course of the disease. Thirty-one patients were treated: 13 patients received a fludarabine or bendamustine-based regimen, 5 chlorambucil based, 5 Ibrutinib, 4 polychemotherapy, 1 obinutuzumab, 2 venetoclax and 1 idelalisib. Treatment was initiated because of the presence of skin lesions in 15 patients. Systemic treatment led to a complete skin response in 74% (23/31) of patients. The 8 patients who did not experience a complete skin response (among which the 5 patients treated with chlorambucil) achieved a partial response of the systemic CLL disease as well.
Conclusion
In this large CLL-LC cohort, we did not find a specific clinical or biological profile associated with LC, nor any difference related to morphology or site of skin lesions. t(14;18) is enriched and we are currently investigating its significance in this atypical clinical presentation of CLL. Our results suggest that CLL patients with cutaneous lesions are not associated with poor prognosis features and they respond well to CLL systemic treatment.
Keyword(s): Chronic lymphocytic leukemia, Mutation analysis