Search PubMed⌕ Search

Biomedical subjects

C D Fletcher

Publications and source records attributed to C D Fletcher.

At least 145 records · Page 8Linked to original sources

Myoid differentiation in dermatofibrosarcoma protuberans and its fibrosarcomatous variant: clinicopathologic analysis of 5 cases.

We report a series of five cases of dermatofibrosarcoma protuberans, four of which were fibrosarcomatous and all of which showed histologic and immunohistochemical evidence of focal myoid/myofibroblastic differentiation (accounting for up to 5% of each tumor). These lesions were identified amongst 208 cases of dermatofibrosarcoma protuberans including 24 examples of the fibrosarcomatous variant. Three of the five patients were male and two were females; all were adults (37-72 years). One case arose on the scalp and two cases each on the abdominal wall and upper trunk. All tumors were less than 5cm in diameter and preoperative duration ranged from 2 months to 10 years. In three cases with follow-up there was no recurrence. Histologically, all tumors were typical fibrosarcomatous or ordinary dermatofibrosarcoma protuberans but for the presence of scattered to confluent nodules and bundles of eosinophilic spindle cells associated with well-defined cytoplasmic margins and vesicular nuclei associated with focal stromal hyalinization. While the typical dermatofibrosarcoma protuberans areas were CD34 positive, the myoid areas were negative for this antibody and positive for smooth muscle actin and pan-muscle actin. All tumors were desmin negative. Recognition of myofibroblastic differentiation in fibrosarcomatous dermatofibrosarcoma protuberans is important not only because it gives support to the theory of a fibroblastic/myofibroblastic line of differentiation for this type of tumor, but also because it might be a source of confusion with other myofibroblastic lesions (e.g. myofibromatosis, adult myofibroma), especially when small biopsies are evaluated.

Adult↗

Correlation between clinicopathological features and karyotype in lipomatous tumors. A report of 178 cases from the Chromosomes and Morphology (CHAMP) Collaborative Study Group.

Soft tissue tumors commonly show cytogenetic abnormalities, some of which are tumor specific. Lipomatous tumors represent the largest category of soft tissue neoplasms, and numerous karyotypic aberrations have been identified. However, clear-cut correlation between morphology and karyotype has not been undertaken on a systematic basis in a double-blind setting. The morphological features and histological diagnosis of 178 lipomatous neoplasms were reviewed independently without knowledge of the clinical data. The consensus diagnoses were then correlated with the clinical findings and compared with the tumors' karyotypes, using G-banded preparations from short-term cultures. The data were collated by a multicenter collaborative group of pathologists, geneticists, and surgeons. Clonal chromosomal abnormalities were identified in 149 cases studied (84%) and, to a large extent, the karyotype correlated with the morphological diagnosis. Specifically, 26 (96%) of 27 myxoid liposarcomas and its poorly differentiated variants showed a t(12;16); 29 (78%) of 37 atypical lipomatous tumors (including 5 dedifferentiated cases) showed ring chromosomes; 74 (80%) of 93 subcutaneous and intramuscular lipomas had karyotypic aberrations affecting mainly 12q, 6p, and 13q; 7 of 8 spindle cell and pleomorphic lipomas had aberrations of 16q; 3 lipoblastomas showed 8q rearrangements; and 2 hibernomas showed 11q abnormalities. We conclude that cytogenetic abnormalities are common in lipomatous tumors, correlate reliably with morphological sub-type in many cases, and can be of diagnostic value in histologically borderline or difficult cases.

Adolescent↗

Tumor suppressor genes and related molecules in leiomyosarcoma.

Soft tissue sarcomas represent a heterogeneous group of mesenchymal malignancies, and the majority of the previous scientific studies that have analyzed the occurrence of cell cycle regulators aberrations within soft tissue sarcomas have dealt with broad categories of different tumors. As a consequence, data concerning single classes of sarcomas are very limited. The authors analyze herein a histologically homogeneous series of 23 cases of leiomyosarcoma of the deep soft tissue. The p53 pathway was studied by investigating the p53 gene and protein, MDM2 protein, and p21waf1 protein. The Rb-cyclin D pathway was analyzed by studying the Rb gene and protein, p16MTS1/INK4A gene and protein, cyclin D1Prad1/bcl1 and cyclin D3 proteins. Aberrations of the p53 pathway were observed in about 16 percent of cases and were limited to the p53 gene. Such a finding contrasts with the higher rates of p53/MDM2 abnormalities reported in other types of sarcomas such as liposarcoma. Interestingly, abnormalities involving the Rb-cyclin D pathway were detected in about 90 percent of cases. The Rb-cyclin D pathway therefore emerges as the preferred target for molecular abnormalities in this subset of soft tissue sarcomas.

Base Sequence↗

Surgical resection of primary soft-tissue sarcoma. Incidence of residual tumour in 95 patients needing re-excision after local resection.

We reviewed retrospectively 236 consecutive patients seen in our soft-tissue sarcoma clinic. Of these, 95 had had a primary soft-tissue sarcoma excised elsewhere, but with histologically inadequate resection margins. All these patients had a secondary and wider re-excision. The tissues removed at the secondary re-excision were examined histologically for the presence of residual tumour. Definite tumour tissue was found in 29 of 55 lower-limb specimens, 16 of 25 upper-limb, 7 of 10 trunk and 4 of 5 head and neck specimens. In 31 cases some residual tumour was visible macroscopically, and in 56 of the 95 patients (59%) the primary tumour had been incompletely excised. Our results indicated that surgical assessment of the adequacy of excision is very inaccurate and that most local recurrences are the consequence of inadequate primary surgery. The large number of patients who had inadequate initial treatment emphasises the need for a co-ordinated multidisciplinary approach to the management of patients with soft-tissue sarcoma.

Adolescent↗

Vascular tumors: an update with emphasis on the diagnosis of angiosarcoma and borderline vascular neoplasms.

It is clear from this selective review that the category of vascular tumors remains a great source of interest and diagnostic challenge because of its complex and heterogeneous constituents. Accurate diagnosis of the relatively infrequent angiosarcomas, with particular emphasis on avoiding overdiagnosis, remains crucial since the clinical outcome is generally very poor, especially when compared with the relatively innocent angiomatous lesions often mistaken for it. Equally, it is important to avoid confusing either spindle cell hemangioendothelioma or tufted angioma with Kaposi's sarcoma inasmuch as the connotations of the latter (especially in young patients) are considerable. Finally, the concept of borderline malignancy in vascular tumors is evolving and is still poorly defined. However, the number of tumors often placed in this category is expanding, and the indolent or unpredictable biologic behavior of these tumors will continue to pose problems and questions for pathologist and clinician alike.

Diagnosis, Differential↗

Gastrointestinal stromal tumors with prominent signet-ring cell features.

Three cases of gastrointestinal stromal tumors characterized by a population of cells displaying prominent signet-ring cell features are described. The tumors occurred in women aged 45 to 74 years and presented as small (< 2.5 cm), well-circumscribed, serosal nodules located within the wall of the stomach, small bowel, and rectum. Histologically, the lesions were characterized by a proliferation of large, round-to-oval cells containing abundant clear cytoplasm with displacement of the nuclei toward the periphery, which imparted to them a striking signet-ring cell configuration. In some areas, the signet-ring cells were seen to merge with short fascicles of spindle cells, whereas in other areas, the tumor cells were associated with prominent deposition of myxoid matrix. Histochemical studies showed glycogen granules within the cytoplasm of the tumor cells in two cases. Immunohistochemical studies showed a heterogeneous pattern of staining, with strong positivity for actin, vimentin, and CD34 in one case; strong vimentin and S-100 protein and weak, focal positivity for actin and CD34 in another; and vimentin positivity alone in the third. The present cases illustrate an unusual morphologic appearance of gastrointestinal stromal tumors that should be distinguished from primary and metastatic mucin-secreting carcinoma and other types of neoplasms with clear cell or signet-ring cell features.

Adenocarcinoma↗

[Early stage Stewart-Treves syndrome: report of 2 cases and review of the literature].

BACKGROUND: Stewart-Treves (S-T) syndrome is a rare from of angiosarcoma occurring as a complication of lymphedema, classically associated with mastectomy and lymph node dissection for breast carcinoma but also occurring in other forms of chronic lymphoedema. Generally S-T syndrome has a very poor prognosis. Recognition in its earliest stages, at least histologically, can be extremely difficult. MATERIALS AND RESULTS: We report two female patients aged 77 and 68 with chronic lymphoedema of the arm complicating for 9 and 8 years respectively ipsilateral mastectomy for breast cancer treated 10 years earlier in both cases. The first developed violaceous macules on the arm and the second presented with a bluish cutaneous nodule on the upper arm. Histologically the first showed lymphangectasia and a dermal proliferation of thin-walled dissecting vessels with only focally slight endothelial atypia ("lymphangiomatosis"), whereas similar architectural features in the second case were associated focally with overt endothelial atypia and micropapillae. These appearances were regarded as pre-malignant (lymphangiomatosis) and malignant (angiosarcoma) respectively. At 3 years follow-up the first patient showed no disease progression, whereas the second patient at her second year of follow-up developed additional nodules. DISCUSSION: In reviewing the literature, approximately 400 cases of angiosarcoma associated with lymphoedema have been reported, of which 360 occurred after ipsilateral mastectomy. Previous controversy as to whether such tumors were truly vascular (rather than simply recurrent carcinoma) has been resolved conclusively in favour of endothelial differentiation. Pathogenetically it seems in these cases that chronic lymphoedema histologically characterized by lymphatic dilatation (lymphangectasia) leads first to proliferation of lymphatics (lymphangiomatosis) with possible slight endothelial atypia. Thereafter there is a gradual continuum of increasing endothelial atypia, followed by multilayering, papillae formation and solid sheet-like tumour. Cumulative published data show that lymphangiomatosis in this clinical setting is premalignant, while the presence of moderate to severe endothelial atypia indicates a diagnosis of (lymph) angiosarcoma. Histological distinction between lymphangiomatosis and ("early") well-differentiated angiosarcoma can be difficult but clearly is of great clinical importance.

Aged↗

Translocation t(12;16)(q13;p11) in myxoid liposarcoma and round cell liposarcoma: molecular and cytogenetic analysis.

Translocation t(12;16)(q13;p11) is regarded as a diagnostic marker for myxoid liposarcoma. Cytogenetic data on round cell liposarcomas and combined myxoid and round cell tumors is scarce, and the genetic basis of progression of myxoid tumors to high grade, round cell lesions is unknown. We have accumulated six round cell, four combined myxoid and round cell, and three myxoid liposarcomas for analysis. t(12;16)(q13;p11) was present in three round cell lesions and was detectable in all of the tumors by DNA analysis. In each tumor type, the CHOP gene in 12q13 was rearranged and fused to the TLS gene in 16p11. A variant TLS-CHOP RNA transcript was detected by polymerase chain reaction but did not correlate with clinicopathological data. No distinguishing cytogenetic or molecular markers for round cell or mixed lesions were found. The histogenic and genetic relatedness of myxoid and round cell liposarcomas is apparent from these data.

Adult↗

Lipomatous tumours of soft tissues: an update.

This review summarizes the clinicopathological features of recently characterized variants of lipomatous tumours of soft tissue, attempts to deal with some difficult conceptual issues relating to adipocytic neoplasms and aims to provide an update on cytogenetic aspects of fatty tumours. Myolipoma is a rare benign neoplasm, occurring most frequently in adults in the deep soft tissue of the abdomen or retroperitoneum, and is composed of irregularly admixed mature adipose and smooth muscle tissues. Chondroid lipoma represents an unusual benign lesion occurring mainly in adult females subcutaneously or in deep soft tissue; it is easily mistaken for myxoid liposarcoma or extraskeletal myxoid chondrosarcoma. Spindle-cell liposarcoma is a variant of well-differentiated liposarcoma quite commonly found in subcutaneous tissue of the shoulder region and upper limbs and is composed of relatively bland-appearing spindle cells mixed with a well-differentiated liposarcomatous component. Recently there has been considerable debate about classification of lipomatous tumours. The term atypical lipoma was proposed for a group of well-differentiated non-metastasizing liposarcomas arising in surgically amenable soft tissues and for deep-seated atypical adipocytic neoplasms that show variation in adipocytic size and atypical stromal cells but lack lipoblasts. However, these neoplasms recur repeatedly and may dedifferentiate and thereby acquire metastatic potential. We use the diagnosis atypical lipoma with caution and propose to use the terms well-differentiated liposarcoma and atypical lipoma interchangeably. The relationship between myxoid and round-cell liposarcoma, which constitutes the morphological spectrum of a single entity, has been clarified but there remain considerable problems in defining likely clinical behaviour. The recent advances in cytogenetic characterization and classification of lipomatous tumours, which is already proving to be of diagnostic importance, are reviewed, and the genetic importance of the distinct chromosomal translocation in myxoid/round cell liposarcoma is briefly discussed.

Adult↗

Report of a symposium on diagnosis and treatment of adult soft tissue sarcomas in the head and neck.

A series of presentations and discussions was held during a symposium on the diagnosis and treatment of adult soft tissue sarcomas in the head and neck (HNSTS). The purpose of this meeting was to define guidelines on diagnosis and treatment of HNSTS. The results of this symposium are summarized and condensed in this report. Recommendations are made for diagnostic strategies and for treatment. Diagnostic efforts in PET scanning and dynamic MRI need to be expanded to detect early recurrences. Firm pathological diagnosis remains the basis for further treatment strategy. Wide surgical excision, if feasible, in combination with radiotherapy is the treatment of choice.

Adult↗

Extranodal follicular dendritic cell sarcoma of the gastrointestinal tract. Morphologic, immunohistochemical and ultrastructural analysis of two cases.

Tumors showing differentiation toward follicular dendritic cells are rare and usually occur in lymph nodes. Their occurrence at extranodal sites was recognized recently. This report documents two further extranodal cases, one arising in the small intestine of a 23-year-old woman and the second in periduodenal retroperitoneal soft tissue of a 63-year-old man. Both neoplasms displayed a typical biphasic morphologic pattern, composed of large cells with indistinct cytoplasmic borders creating a syncytial appearance, admixed with spindle cell areas resembling malignant fibrous histiocytoma, and infiltrated by numerous small T lymphocytes. Expression of CD21 and CD35, together with ultrastructural demonstration (in one case) of long cytoplasmic processes connected by desmosomes, confirmed follicular dendritic cell differentiation. One case also expressed HLA-DR, and both showed aberrant epithelial membrane antigen staining. Neither tumor showed CD45 expression. In both cases the tumors were treated by local excision. Case 1 has shown an unusually aggressive course with extensive intraperitoneal recurrence. The biphasic morphologic pattern and tumor immunophenotype are discussed in relation to increasing evidence of immunophenotypic and morphologic heterogeneity of normal follicular dendritic cells.

Adult↗

Cutaneous intraneural glomus tumor.

The unusual occurrence of a glomus tumor within a small, deep dermal nerve is reported. This phenomenon has been described previously only once in the literature. The lesion appeared as a painful cutaneous nodule in the shoulder of a 67-year-old woman. Microscopically, a typical solid, smooth muscle actin-positive glomus tumor was seen, encircled completely by neural tissue in the deep dermis. There was no extension of the tumor beyond the nerve. Immunohistochemically, the nerve fibers surrounding and within the tumor were positive for S-100 protein and neurofilament. The presence of perineurium surrounding the glomus tumor was confirmed by a layer of epithelial membrane antigen-positive cells. In view of the absence of normal glomus bodies in the nerves, an origin from a less specialized perivascular cell is proposed.

Actins↗