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).

Microlinguistic deficits in the narrative discourse of adults with traumatic brain injury.

BACKGROUND: Recent studies of microlinguistic impairments in the narrative discourse of adults with traumatic brain injury (TBI) have applied syntactic analyses, with some noting no deficits and others specific problems with sentence formulation. An alternative approach to examining the microlinguistic dysfunction in the discourse of individuals with TBI is through the use of propositional analysis. The advantage of propositional analysis is that it enables one to assess semantic complexity of utterances apart from sentence structure and grammaticality. AIMS: The present study applied propositional analysis to the story narratives of participants with TBI and participants with no brain injury (NBI). Specifically, the mean number of propositions within a sentence was tallied, in other words the participants' ability to insert multiple ideas into single surface sentences. It was hypothesized that the participants with TBI would produce fewer propositions per sentence because of organizational problems than the participants with NBI, regardless of level of education. METHODS AND PROCEDURES: Two story narratives (retelling and generation) previously elicited from the two participant groups (TBI (n = 53) and NBI (n = 42)) were analysed. For each language sample, the number of propositions was tallied and divided by the number of T-units. The resulting number, the propositional complexity index (PCI), was the average number of predicates per sentence. OUTCOMES AND RESULTS: Results indicated that the group with TBI produced significantly fewer propositions per T-unit. CONCLUSIONS: The present findings are in harmony with the notion that the participants with TBI studied presented with impairments of both micro- and macrolinguistic processes involved with the organization of semantic information in discourse. Clinical implications are discussed.

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.

The influence of argument-structure complexity on the use of auxiliary verbs by children with SLI.

The purpose of the present study was to investigate the influence of argument-structure complexity on the omission of auxiliary be verbs in a group of children with specific language impairment (SLI). These children were compared to a group of younger, normally developing children matched for mean length of utterance (MLU) and a group of children matched for chronological age (CA). Using a story-completion task, the children (N = 30) were required to produce sentences of varying length and argument-structure complexity. The results of the study indicated that the children with SLI omitted more auxiliary forms than either the MLU or CA controls. In addition, both the children with SLI and the MLU controls were more likely to omit the auxiliary forms when attempting sentences with greater argument-structure complexity. These results suggest that argument-structure complexity may be a contributing factor to children's omissions of grammatical morphemes.

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.

Locus of functional impairment in the production of speech rhythm after brain damage: a preliminary study.

This acoustic-perceptual, multiple-case study of the Rhythm Rule (RR) in English, a phonological phenomenon whereby adjacent stresses are adjusted to avoid "stress clash" (e.g., thirTEEN vs THIRteen MEN), was undertaken to identify the locus of functional impairments in speech prosody in different aphasic syndromes. Subjects included two left brain-damaged aphasic patients (1 fluent, 1 nonfluent), one right brain-damaged nonaphasic patient, and one nonneurological control. They were instructed to read sentences including experimental (bisyllabic "double-stressed" words) and matching control (bisyllabic "initial-stressed" words) phrases of increasing length. Results of acoustic and perceptual measures indicated that rhythmic disturbances associated with the RR emerged regardless of lesion site. The locus of functional impairment was isolated to phonetic implementation of the RR, as opposed to either loss of word-level stress or loss of the RR. Findings suggest that neural substrates of speech prosody are broadly distributed in the left and right cerebral hemispheres.

Three accounts of the grammatical morpheme difficulties of English-speaking children with specific language impairment.

Several hypotheses have been offered to explain the grammatical morpheme difficulties observed in the speech of children with specific language impairment. Three of the accounts that could be evaluated in English were the focus of this study: the extended optional infinitive account, the implicit rule deficit account, and the surface account. Preschoolers with specific language impairment, a group of age controls, and a group of younger children matched for mean length of utterance were evaluated in their use of several theory-relevant grammatical morphemes. The findings revealed advantages for both the surface and extended optional infinitive hypotheses. In contrast, a test of the predictions based on the implicit rule deficit account suggested that the children studied here were not experiencing a deficit of this type.