Long-term results of treatment of advanced dermatofibrosarcoma protuberans (DFSP) with imatinib mesylate - The impact of fibrosarcomatous transformation.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is rare, infiltrating dermal neoplasm, characterized by indolent growth and low probability of metastases. The first effective systemic therapy in DFSP introduced into clinical practice was imatinib, demonstrating high activity in advanced cases. The aim of the study was to perform an analysis of patients with advanced DFSP treated with imatinib, with or without surgery, in routine clinical practice with long-term follow-up. PATIENTS AND METHODS: We analyzed the data of 31 Caucasian patients (14 male, 17 female; median age 56 years) with locally advanced/initially inoperable and/or metastatic DFSP who started therapy with imatinib at initial dose 800 mg daily between 12/2004 and 07/2014. All diagnoses were confirmed cytogenetically for the presence of specific COL1A1-PDGFB fusion. Median follow-up time was 5.3 years. RESULTS: Metastases were present in 15 cases (8 - lungs, 5 - soft tissue, 2 - lymph nodes). Fibrosarcomatous transformation (FS-DFSP) was confirmed in 16 patients (52%). 5-year progression-free survival (PFS) rate was 58% (median 6.8 years), 5-year overall survival (OS) rate was 64% (median time for OS was not reached). The shorter PFS and OS correlated with FS-DFSP and presence of metastatic disease. 5-year PFS rate was 93% for classic DFSP and 33% for FS-DFSP. The best overall responses were: 21 partial responses (68%, including 8 FS-DFSP, but the responses were shorter than for classic DFSP), 6 stable disease (19%) and 4 progressive diseases (13%). Thirteen patients (47%) underwent resection of residual disease and nine of them remained free of disease, although imatinib was discontinued. Median survival after progression on imatinib was 19 months, and longer survival were observed only in cases were rescue surgery/radiotherapy was possible. CONCLUSIONS: Our results indicate the long-term activity of imatinib in therapy of inoperable and/or metastatic cases of DFSP, including FS-DFSP. Some DFSP patients initially evaluated as unresectable/metastatic or necessitating mutilating surgery turned resectable after imatinib therapy and this rational approach leading to complete remission maybe potentially curative.

Neoplastic and nonneoplastic lesions in aging mice of unique and common inbred strains contribution to modeling of human neoplastic diseases.

The evaluation of spontaneous lesions in classical inbred strains of mice has become increasingly important because genetically engineered mice (GEMs) are created on these backgrounds. Novel inbred strains-genetically diverse from classic strains-are valuable both as a new background for GEM mice and to increase the genetic variation found in laboratory mice. Newly arising spontaneous genetic alterations in commonly used strains may also lead to new and valuable mouse models of disease. This report evaluates gross and histological lesions in relatively new, classic, and rarely explored mouse inbred strains. Pathological lesions of 1273 mice from 12 inbred strains (129S1/SvW, A.CA-H2(f) /W, AKR/W, BALB/cW, BN/aW, C57BL/6 W, C57BL/10 W, C3H/W, C3H (wad) /W, CBA/W, DBA/2 W, and WOM/W) are reported. BN/aW, WOM/W, and C3H (wad) /W are novel inbred strains produced and maintained in the Department of Genetics and Laboratory Animal Breeding at the Center of Oncology, Warsaw, Poland. Both neoplastic and nonneoplastic lesions were examined. The prevalence of lung neoplasms was significantly higher in A.CA-H2(f) /W (33.3%) and BALB/cW (33.8%) mice (P < .01). The prevalence of liver neoplasms was significantly higher in the CBA/W strain (P < .01). Mammary gland neoplasms arose at a greater frequency in C3H/W mice (P < .01). The occurrence of uterine neoplasms was higher in DBA/W and 129S1/SvW mice. AKR/W and WOM/W mice developed T-cell lymphoblastic lymphoma with high frequency (110/121 [90.9%] and 159/175 [90.9%], respectively) before 1 year of age. The occurrence of nonneoplastic lesions in the kidneys of BN/aW mice was increased (P < .01).

Family with Li-Fraumeni syndrome and no evidence of a germline mutation of the p53 gene or chromosomal aberrations.

Li-Fraumeni syndrome is a rare autosomal, dominant trait of diverse types of cancers in children and young adults, with a predominance of soft tissue sarcomas, osteosarcomas, brain tumours, adrenocortical and breast carcinomas, as well as leukaemias. We present a family with an unusual cancer history fulfilling the criteria of Li-Fraumeni syndrome. Mutational analysis of the p53 gene in constitutional DNA of several affected members of the family did not show any germline p53 defect. Cytogenetic studies did not reveal any structural aberrations.

Chronic lymphocytic leukaemia presenting with central nervous system involvement.

A 68-year-old man presented with hemiparesis, lymphocytosis, and cerebral lesions on MRI. Flow cytometry of blood, bone marrow and cerebrospinal fluid showed B-CLL lymphocytes with bright CD20 expression, sIg, and absence of CD23 antigen. Fluorescence in situ hybridisation showed trisomy 12 in 50% of analysed peripheral mononuclear cells. The patient died 6 months after the diagnosis. Rapidly progressive and fatal course of the disease was consistent with known bad prognostic significance of CD20 bright expression and trisomy 12.