Biomedical subjects

C D M Fletcher

Publications and source records attributed to C D M Fletcher.

10 recordsLinked to original sources

PubMed2006

EGFR amplification and lack of activating mutations in metaplastic breast carcinomas.

Metaplastic breast carcinomas are reported to harbour epidermal growth factor receptor (EGFR) overexpression in up to 80% of the cases, but EGFR gene amplification is the underlying genetic mechanism in around one-third of these. In this study, EGFR gene amplification as defined by chromogenic in situ hybridization and protein overexpression was examined in a cohort of 47 metaplastic breast carcinomas. Furthermore, the presence of activating EGFR mutations in exons 18, 19, 20, and 21 was investigated. Thirty-two cases showed EGFR overexpression and of these, 11 (34%) harboured EGFR gene amplification. In addition, EGFR amplification showed a statistically significant association with EGFR overexpression (p < 0.0094) and was restricted to carcinomas with homologous metaplasia. Ten cases, five with and five without EGFR amplification, were subjected to microarray-based CGH, which demonstrated that EGFR copy number gain may occur by amplification of a discrete genomic region or by gains of the short arm of chromosome 7 with a breakpoint near the EGFR gene locus, the minimal region of amplification mapping to EGFR, LANCL2, and SEC61G. No activating EGFR mutations were identified, suggesting that this is unlikely to be a common alternative underlying genetic mechanism for EGFR expression in metaplastic breast carcinomas. Given that metaplastic breast carcinomas are resistant to conventional chemotherapy or hormone therapy regimens and that tumours with EGFR amplification are reported to be sensitive to EGFR tyrosine kinase inhibitors, these findings indicate that further studies are warranted to explore EGFR tyrosine kinase inhibitors as potential therapeutic agents for metaplastic breast carcinomas harbouring amplification of 7p11.2.

Breast Neoplasms↗

PubMed2006

Editorial.

Explore the source record for details and available documents.

Periodicals as Topic↗

PubMed2006

The evolving classification of soft tissue tumours: an update based on the new WHO classification.

Tumour classifications have become an integral part of modern oncology and, for pathologists, they provide guidelines which facilitate diagnostic and prognostic reproducibility. In many organ systems and most especially over the past decade or so, the World Health Organization (WHO) classifications have become pre-eminent, partly enabled by the timely publication of new "blue books" which now incorporate detailed text and copious illustrations. The new WHO classification of soft tissue tumours was introduced in late 2002 and, because it represents a broad consensus view, it has gained widespread acceptance. This review summarizes the changes, both major and minor, which were introduced and briefly describes the significant number of tumour types which have been first recognized or properly characterized during the past decade. Arguably the four most significant conceptual advances have been: (i) the formal recognition that morphologically benign lesions (such as cutaneous fibrous histiocytoma) may very rarely metastasize; (ii) the general acceptance that most pleomorphic sarcomas can be meaningfully subclassified and that so-called malignant fibrous histiocytoma is not a definable entity, but instead represents a wastebasket of undifferentiated pleomorphic sarcomas, accounting for no more than 5% of adult soft tissue sarcomas; (iii) the acknowledgement that most lesions formerly known as haemangiopericytoma show no evidence of pericytic differentiation and, instead, are fibroblastic in nature and form a morphological continuum with solitary fibrous tumour; and (iv) the increasing appreciation that not only do we not know from which cell type(s) most soft tissue tumours originate (histogenesis) but, for many, we do not recognize their line of differentiation or lineage--hence an increasing number of tumours are placed in the "uncertain differentiation" category.

Humans↗

PubMed2006

Postradiation vascular proliferations: an increasing problem.

The occurrence of cutaneous vascular lesions is a rare but well-documented complication of radiation treatment and may be associated with significant morbidity as well as mortality. The overall incidence is low but appears to be rising due to a change in the prevailing treatment of breast carcinoma with increased use of radiation in the setting of breast-conserving therapy for stage 1 and 2 disease. The spectrum of postradiation vascular lesions is wide and ranges from atypical vascular lesions with reportedly benign clinical behaviour to frank cutaneous angiosarcoma. There is, however, significant clinical as well as histological overlap. It is frequently difficult to classify these postradiation vascular lesions accurately and they create an emerging diagnostic and therapeutic challenge to both pathologists and clinicians. Experience with these vascular lesions is very limited, and this article aims to provide an overview of our current understanding and concept of radiation-associated vascular lesions with focus on their clinical and histological presentation as well as behaviour and treatment.

Diagnosis, Differential↗

PubMed2006

PEComa: what do we know so far?

PEComas (tumours showing perivascular epithelioid cell differentiation) are a family of related mesenchymal neoplasms that include angiomyolipoma, lymphangiomyomatosis, clear cell "sugar" tumour of the lung, and a group of rare, morphologically and immunophenotypically similar lesions arising at a variety of visceral and soft tissue sites. These tumours all share a distinctive cell type, the perivascular epithelioid cell or "PEC' (which has no known normal tissue counterpart). PEComas show a marked female predominance and are composed of nests and sheets of usually epithelioid but occasionally spindled cells with clear to granular eosinophilic cytoplasm and a focal association with blood vessel walls. PEComas appear to arise most commonly at visceral (especially gastrointestinal and uterine), retroperitoneal, and abdominopelvic sites, with a subset occurring in somatic soft tissue and skin. Nearly all PEComas show immunoreactivity for both melanocytic (HMB-45 and/or melan-A) and smooth muscle (actin and/or desmin) markers. A subset of PEComas behave in a malignant fashion. This review examines the members of the PEComa family, with an emphasis on lesions arising outside of the kidney, lung and liver, and discusses preliminary evidence for pathological features that might predict malignant behaviour.

Actins↗

PubMed2006

Haemosiderotic fibrolipomatous tumour (so-called haemosiderotic fibrohistiocytic lipomatous tumour): analysis of 13 new cases in support of a distinct entity.

AIMS: To describe 13 new cases of a rare soft tissue neoplasm currently known as haemosiderotic fibrohistiocytic lipomatous tumour (HFHLL) and to further its characterization. METHODS AND RESULTS: Patients were eight females and five males, aged 8 months to 74 years. Lesions ranged in size from 10 to 130 mm (median 45). Twelve of 13 lesions were located in the ankle/foot region; one involved the hand. Grossly the lesions were fatty/gelatinous or lipoma-like. They were characterized by varying proportions of mature adipocytes and fibroblastic spindle cells, associated with haemosiderin pigment present predominantly in macrophages within the spindle cell component. Dissecting between adipocytic lobules were septa containing short spindle cells with streaming, swirling or honeycomb growth patterns. Most tumours contained scattered osteoclast-like giant cells. Mitoses were rare and only one case showed mild atypia. Immunohistochemistry in 10 cases showed 7/9 CD34+; all were negative for smooth muscle actin, CD68, S100 and desmin. Follow-up in nine cases ranging from 1 to 130 months (median 12) showed local recurrence in three but no metastasis. CONCLUSIONS: So-called HFHLL, better termed haemosiderotic fibrolipomatous tumour, is a distinct lesion characterized by an admixture of fibroblastic spindle cells, mature adipocytes and haemosiderin pigmentation, shows a predilection for the distal extremities and quite often recurs locally.

Adult↗

PubMed2006

ALK expression in pseudosarcomatous myofibroblastic proliferations of the genitourinary tract.

AIMS: Pseudosarcomatous myofibroblastic proliferation of the genitourinary tract is rare and may develop after trauma or spontaneously. The aim of this study was to characterize further the clinicopathological features of these lesions and to examine their relationship to inflammatory myofibroblastic tumour (IMT). METHODS AND RESULTS: Twenty-seven cases of pseudosarcomatous myofibroblastic proliferation were analysed. There were seven males and 20 females; median age was 37 years (range 16-88). Most lesions were from the bladder (n = 21), while others were in the urethra, vulva, vagina, rectum and retrovesical space. Median tumour size was 30 mm (range 6-120 mm). Seven cases (25%) had a history of prior trauma or surgery. Three cases recurred locally but not destructively. The tumours had fasciitis-like features including bland spindle cells with evenly distributed chromatin, admixed inflammatory cells (mainly lymphocytes) and often a myxoid stroma. Immunohistochemistry showed positivity for smooth muscle actin in 14/20 cases, keratin in 8/19, desmin in 7/20 and anaplastic lymphoma kinase (ALK) in 10/21 cases. Fluorescent in situ hybridization was performed in six ALK+ cases; all were negative for ALK gene rearrangement. CONCLUSIONS: Pseudosarcomatous myofibroblastic proliferations of the genitourinary tract may show ALK immunopositivity but do not show consistent ALK rearrangement. Given subtle morphological differences and more consistently benign behaviour, their relationship to inflammatory myofibroblastic tumour at other sites remains uncertain.

Actins↗

PubMed2003

Prognostic information in soft tissue sarcoma using tumour size, vascular invasion and microscopic tumour necrosis-the SIN-system.

We have earlier devised a system for soft tissue sarcoma (STS), based on three negative prognostic features: large tumour size, vascular invasion, and microscopic tumour necrosis, the SIN-system. Tumours which exhibit 2 or 3 of these features are categorised as high-risk, the others as low-risk. We have now tested this system for reproducibility both as regards recognition of its components, and as regards prognostic strength in patients from another institution. We have also compared it with the American Joint Committee on Cancer (AJCC) system. 200 patients with STS were analysed, all had been treated by surgery, in 97 patients combined with radiotherapy. The median follow-up for the 117 survivors was 10 (1.5-27) years. Without knowledge of the clinical data, three groups of pathologists independently reviewed original slides from all of the tumours. Based on the factors, the tumours were classified as high-risk or low-risk. The prognostic strength was compared using the results obtained by the different observers. Concordance in recognition of vascular invasion, tumour necrosis, and overall grading was seen in 156 (78%), 154 (77%), and 167 (84%) of the 200 tumours, respectively. Based on the different observers' grading, the cumulative 5-year metastasis-free survival rate (MFSR) varied for patients with low-risk tumours between 0.85 and 0.80, and for patients with high-risk tumours between 0.48 and 0.43. The Kappa-value for grading between all three groups of observers was 0.77. The SIN-system gave more clinically useful prognostic information than the AJCC system. Useful prognostic information in STS can be obtained by using tumour size, vascular invasion and microscopic tumour necrosis. This system provides two distinct prognostic groups, and has a high reproducibility.

Adolescent↗

PubMed2003

Synovial sarcoma in older patients: clinicopathological analysis of 32 cases with emphasis on unusual histological features.

AIMS: To analyse the clinicopathological features of synovial sarcoma presenting in patients over 60 years of age, an uncommon subset which have not been specifically studied. METHODS AND RESULTS: Thirty-two cases of primary synovial sarcoma in patients aged > or =60 years were retrieved from the authors' consultation files. These were analysed histologically and immunohistochemically and clinical follow-up was obtained in 26 cases (median duration 41 months). Mean age at diagnosis was 71.6 years (range 60-84) with 19 females and 13 males. Anatomical sites were lower limb (n = 13), upper limb (n = 5), lung/pleura (n = 5), trunk (n = 4), head/neck (n = 3), mediastinum (n = 1) and scrotum (n = 1). Histologically, 23 were monophasic and nine were biphasic; 14 were poorly differentiated, of which five showed focally marked pleomorphism. Unusual features in two cases each included organoid nodules, granular cell change, squamous metaplasia and papillary architecture. Ten patients developed local recurrence and 11 developed metastases, of whom seven died. Large tumour size, poorly differentiated morphology and high mitotic rate correlated with poor outcome. CONCLUSIONS: Less than 10% of synovial sarcomas occur in patients over 60, in which age group this diagnosis is often not considered. Despite inevitable bias in consultation material, it seems that these cases, when compared with younger age groups, more often show poorly differentiated histology and more often develop at unusual locations.

Aged↗

PubMed2002

Malignant myopericytoma: expanding the spectrum of tumours with myopericytic differentiation.

AIMS: The spectrum of tumours showing myopericytic differentiation is increasingly being defined and includes lesions such as myofibroma and infantile haemangiopericytoma. Here we seek to describe for the first time and clinicopathologically characterize examples of malignant myopericytoma. METHODS AND RESULTS: Five cases of malignant myopericytoma were identified in the authors' consultation files. Immunostains were performed and clinical information was obtained. Tumours arose in three females and two males (median age 67 years, range 19-81 years) on the neck, arm, thigh and foot. One patient presented with disseminated metastases. One patient had a prior history of multiple benign myopericytomas in the same location. Four patients developed metastases and three died within 1 year. Tumours were composed of highly mitotic myoid-appearing ovoid-to-spindle cells showing at least focally striking perivascular orientation resembling that seen in benign myopericytoma; three cases were focally fascicular and three showed thin-walled branching vessels. All tumours showed at least focally prominent positivity for smooth muscle actin. One case showed dot-like desmin positivity. CONCLUSIONS: In reporting examples of malignant myopericytoma, we further characterize and broaden the morphological spectrum of myopericytic neoplasms. Available data indicate that malignant myopericytomas are associated with aggressive clinical behaviour.

Adult↗