PubMed HealthSearch

Biomedical subjects

C D Fletcher

Publications and source records attributed to C D Fletcher.

At least 19 recordsLinked to original sources

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

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

Lymphangiomatosis of the limbs. Clinicopathologic analysis of a series with a good prognosis.

Six cases of a distinctive but poorly recognized variant of lymphangiomatosis with predominant or exclusive involvement of the soft tissues of the limb/limb girdle are described. The six patients were male and presented with slowly progressive swelling of the involved limb. The age of onset was at birth (three cases), 3 months (one case), 11 years (one case) and 12 years (one case). Five patients had involvement of the lower extremity and one of the right upper extremity. Three patients had concomitant asymptomatic bone involvement either in the affected limb (two cases) or in distant bones (one case). Only one patient had visceral involvement that was limited to the ipsilateral thorax and was associated with chylothorax. Diagnosis was confirmed in all but one patient by lymphangiography. Treatment consisted principally of surgical reduction with significant clinical improvement. No patient later developed systemic involvement and the clinical course was benign. The bone lesions did not progress in any patient. Histologically, each case was characterised by interconnecting, dilated lymphatic spaces, lined by a single, attenuated layer of endothelial cells, involving the dermis, subcutis, and occasionally, underlying fascia and skeletal muscle with characteristic and extensive "dissection" of collagen and surrounding normal adnexal structures. Despite the absence of red blood cells in the vascular spaces, interstitial hemosiderin deposition was prominent in four cases. As opposed to most cases of lymphangiomatosis, which usually have extensive visceral involvement associated with a very poor prognosis, involvement in this variant is limited almost exclusively to soft tissues of the limb and bone and is associated with good prognosis.

Arm

Immunohistochemistry of MyoD1 in adult pleomorphic soft tissue sarcomas.

Adult pleomorphic rhabdomyosarcomas are difficult to distinguish from other pleomorphic soft tissue sarcomas. Immunostaining with the monoclonal antibody MyoD1 5.8A has recently shown promise as a sensitive and specific marker of rhabdomyosarcomas of childhood. To determine the usefulness of MyoD1 in distinguishing adult pleomorphic rhabdomyosarcoma from other pleomorphic sarcomas, we studied 21 cases of pleomorphic sarcoma, including six cases diagnosed as rhabdomyosarcoma. Immunostaining was accomplished using monoclonal antibodies against MyoD1, desmin, alpha-smooth-muscle actin, and muscle-specific actin on cryostat sections of frozen tumor. All cases of pleomorphic rhabdomyosarcoma stained positively with both desmin and MyoD1. Five cases diagnosed as nonrhabdomyosarcomatous pleomorphic sarcomas stained positively with desmin, but only one showed weak MyoD1 positivity. Three of these five cases were also positive with alpha-smooth-muscle actin. The results of this study suggest that the sensitivity and specificity of the MyoD1 antibody in the differential diagnosis of adult pleomorphic soft tissue sarcomas approaches that seen in pediatric rhabdomysarcomas.

Adult

Atypical and malignant variants of ossifying fibromyxoid tumor. Clinicopathologic analysis of six cases.

Ossifying fibromyxoid tumor (OFMT) of soft parts is a recently defined fibro-osseous neoplasm, the biologic behavior of which is generally regarded as benign. We report six variant cases of OFMT with histologic features of malignancy, two of which behaved aggressively. All these tumors arose in the extremities of adults (aged 36-76 years), and five of the six were subcutaneous. Four patients were men. Macroscopically, all the tumors were well circumscribed and somewhat lobulated. Cardinal morphologic features included lobules of round to spindled cells within a fibromyxoid matrix and randomly distributed, often centrally located osteoid within which were plump neoplastic cells. In contrast to typical OFMT, a hypocellular, cytologically benign, lamellar bony shell was observed only focally; cellularity was increased (four cases), and mitotic activity was frequent, exceeding two mitotic figures per 10 high-power fields (three cases). One case associated with metastases was morphologically bland. Immunohistochemically, positivity for S-100 protein was observed in the primary tumors of three cases and in the pulmonary metastasis of a fourth. Desmin was positive in one case. Ultrastructural features in three cases were very similar to usual OFMT. Clinical follow-up revealed local recurrence in two cases; one patient has developed recurrent pulmonary metastases. We believe these findings support the view that some atypical cases of OFMT exhibit morphologic patterns that might predict more aggressive behavior.

Adult

Aneurysmal benign fibrous histiocytoma: clinicopathological analysis of 40 cases of a tumour frequently misdiagnosed as a vascular neoplasm.

Forty cases of the distinctive but poorly recognized aneurysmal variant of cutaneous fibrous histiocytoma are described. These tumours presented most commonly in middle-age adults, with a slight predilection for females. Anatomical distribution was wide with most cases occurring in the lower limb/limb girdle (50%), upper limb/limb girdle (20%) and trunk (17%). Lesional size ranged from 0.5 cm to 4 cm. Haemorrhage accounted for the rapid clinical growth of some lesions and the frequent clinical confusion with a cyst, a melanocytic lesion or a haemangioma. Five (19%) of the twenty-six cases with follow-up (mean duration 2.5 years) recurred locally, twice in two cases. One of these cases had involvement of a regional lymph node in the second recurrence, most likely as a result of direct local extension. Distinctive histological features were prominent blood-filled spaces, varying from artefact-like clefts to cystic areas mimicking cavernous vascular channels but devoid of an endothelial lining, prominent haemosiderin deposition, numerous siderophages and giant cells, and a moderate mitotic rate. Despite the presence of prominent secondary changes due to haemorrhage, all cases showed cellular polymorphism, hyalinized collagen bundles surrounded by tumour cells in the periphery of the lesion and 88% showed some degree of epidermal hyperplasia, as seen in common fibrous histiocytoma. Immunohistochemistry (ABC method) revealed only vimentin and, rarely, focal smooth muscle actin positivity. CD68 was positive in some reactive macrophages only. Stains for CD31, CD34, desmin and factor XIIIa were negative in all cases tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Pseudomalignant perineurial invasion in cellular ('infantile') capillary haemangiomas.

One hundred and sixty-eight cellular ('infantile') capillary haemangiomas were assessed for the presence of perineurial invasion, a feature that can lead to the erroneous diagnosis of malignancy. Fourteen tumours (8%) showed unequivocal, usually prominent, involvement of small and medium sized nerves. Eleven of these lesions presented in infants at birth or shortly thereafter, two in young adults and one in a middle-aged adult. Ten patients were females. Ten of the lesions arose in the head and neck region, one in the arm, one in the chest wall, and in two the site was not stated. Follow-up revealed a local recurrence in only one of six cases. Histologically, all cases were typical pure capillary haemangiomas composed of lobules of small blood vessels, lined by bland endothelial cells, involving the dermis, subcutis or both. One case was an intramuscular capillary haemangioma. Long-standing cases, especially those in adults, were less cellular, with focal fibrosis and a myxoid stroma. Neural invasion was detected either in the centre or at the periphery of tumour lobules and was characterized by the presence of variable numbers of capillaries within the perineurium and in close contact with Schwann cells. This feature was highlighted by immunostaining for S-100 protein and EMA. In one case, extensive invasion of medium-sized deep dermal veins was also present, focally simulating an intravascular pyogenic granuloma. This study demonstrates that perineurial invasion in infantile capillary haemangiomas is a relatively common finding and should not be regarded as evidence of malignancy.

Adolescent

Low grade fibromyxoid sarcoma: clinicopathological analysis of eleven new cases in support of a distinct entity.

Low grade fibromyxoid sarcoma is a recently recognized, uncommon soft tissue neoplasm with a tendency to develop in deep soft tissue of young adults. Diagnostic criteria have not been well defined and this tumour has not been widely accepted as a distinct entity. Eleven new cases are reported here for which reproducible histological features are described and in which the immunohistochemical profile of the tumour cells is documented for the first time. Ten of the eleven patients were male and the majority were young or middle-aged adults (median age 45 years). All except one of the tumours were situated in deep soft tissue. Lower limb (four cases) and chest wall (three cases) were the commonest primary sites; one case each arose in the groin, buttock, axilla and retroperitoneum. Follow-up (median duration 6 years) was available in nine patients. Six developed local recurrence and in five cases recurrences were multiple. Pulmonary metastasis occurred in one patient. All tumours were characterized by the presence of bland spindle cells, showing a mainly whorled or focally linear arrangement, set in alternating areas with a fibrous or myxoid stroma. Tumour cells were small, spindle to stellate, with poorly defined, palely eosinophilic cytoplasm and hyperchromatic ovoid nuclei. Most tumour cells showed strong staining with antibodies to vimentin, while occasional cells stained positively for actin, desmin and cytokeratin, in keeping with focal myofibroblastic differentiation. Ultrastructural examination in one case revealed features of fibroblasts. Careful consideration of the morphological and immunohistochemical features of these tumours permits a positive diagnosis of low grade fibromyxoid sarcoma and allows its distinction from a number of other benign and malignant soft tissue neoplasms.

Adolescent

Two categories of synovial sarcoma defined by divergent chromosome translocation breakpoints in Xp11.2, with implications for the histologic sub-classification of synovial sarcoma.

Molecular analysis of a new series of synovial sarcomas confirms that t(X;18)(p11.2;q11.2) breakpoints occur at two distinct regions on Xp designated SS1 and SS2. Breakpoint position correlates with tumor phenotype. Monophasic tumors with no evidence of glandular components have breakpoints within the SS2 region in Xp11.21, and biphasic tumors with a focal poorly differentiated or extensive glandular structure have breakpoints within the SS1 region in Xp11.23.

Adolescent

Giant cell angiofibroma. A distinctive orbital tumor in adults.

A series of seven cases of a previously unrecognized potentially recurrent tumor occurring in the orbit of adult patients is reported. This lesion shows histologic appearances intermediate between, but distinct from, solitary fibrous tumor and giant cell fibroblastoma of soft tissue. Morphologically it is characterised by a richly vascularized, patternless spindle-cell proliferation containing pseudovascular spaces. Multinucleate giant cells (often of floret type) and cells with large, rounded nuclei are present both in the cellular areas and also lining the pseudovascular spaces. The stroma is variably collagenized or sometimes myxoid. Immunohistochemically, the tumor cells exhibit positivity for vimentin and CD34. Follow-up in five cases (median duration 24 months) revealed local recurrence in one patient and persistent tumor in another. The clinical and morphologic features enable distinction of this lesion from both solitary fibrous tumor and giant cell fibroblastoma, and we suggest the designation "giant cell angiofibroma of the orbit".

Adult

Immunohistochemistry and DNA flow cytometry in soft-tissue sarcomas.

Immunohistochemistry has a major role as an adjunct to light microscopy in the diagnosis and classification of soft tissue sarcomas. Immunohistochemical analysis of proliferation markers appears so far to add very little to accurate and experienced histologic typing of soft-tissue sarcomas. Immunohistochemical assessment of tumor suppressor genes and oncogene products gives an insight into pathogenetic mechanisms but does not appear to correlate reliably with clinical outcome. Analysis of ploidy by DNA flow cytometry does not separate benign from malignant lesions, and assessment of cell proliferation by this method does not seem to predict clinical behavior accurately.

Biomarkers, Tumor

Soft tissue sarcomas that mimic benign lesions.

Although it is well known that a variety of benign mesenchymal neoplasms and reactive proliferations may mimic sarcomas, the fact that some types of sarcoma commonly are misinterpreted as benign is less widely appreciated. This review considers five such lesions in soft tissue: low grade fibromyxoid sarcoma, low grade myxofibrosarcoma (myxoid "MFH"), well differentiated liposarcoma (atypical lipoma), epithelioid sarcoma, and so-called inflammatory fibrosarcoma. Principal reasons for their underrecognition are their generally bland cytology, often relative hypocellularity, and indolent clinical course. Common to several of these lesions, however, is a tendency for histological and hence biological progression in local recurrences, underlining the importance of accurate diagnosis and adequate treatment of the primary lesion. This review considers the principal clinicopathologic features, differential diagnosis and (where appropriate) nosologic status of this treacherous group of neoplasms.

Connective Tissue