Biomedical subjects

C D Fletcher

Publications and source records attributed to C D Fletcher.

At least 163 records · Page 9Linked to original sources

PubMed1995

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↗

PubMed1995

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↗

PubMed1995

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↗

PubMed1995

Recent developments in soft tissue tumors.

This article reviews the clinicopathological features of several recently described soft tissue tumours, namely ossifying fibromyxoid tumour, angiomyofibroblastoma, epithelioid angiosarcoma, retiform haemangioendothelioma, intra-abdominal desmoplastic small cell tumour, spindle cell liposarcoma and low grade fibromyxoid sarcoma. Conceptual changes are also discussed. These include the relationship between Ewing's sarcoma and peripheral primitive neuroectodermal tumour, the proposed use of the term atypical lipoma for a subset of well differentiated liposarcomas, and the occurrence at a wide variety of sites of inflammatory myofibroblastic lesions of uncertain biological potential. In addition, advances in the study of soft tissue lesions at the molecular and cytogenetic levels are outlined, with particular emphasis on the recent identification of tumour-specific karyotypic abnormalities in a wide variety of sarcomas.

Humans↗

PubMed1995

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↗

PubMed1995

Inflammatory leiomyosarcoma: a morphological subgroup within the heterogeneous family of so-called inflammatory malignant fibrous histiocytoma.

Twelve cases of inflammatory leiomyosarcoma are presented. These tumours arose in the deep soft tissues of the trunk and proximal limbs. The age of the patients ranged from 13-53 years (median 36 years); there was an approximately equal sex ratio. Follow-up data was available for nine patients (mean duration 3.3 years); local recurrence occurred in three and lung metastases in one. Lesions were spindle cell neoplasms with fascicular areas which occupied between 5% and 80% of the tumour. Areas with a distinct storiform pattern were also seen in 10 cases. A prominent inflammatory cell component was evident in all tumours, often masking the neoplastic spindle cells. Histiocytes were identified in all cases, with aggregates of xanthoma cells seen in eight tumours. In 10 cases there was also a dense lymphoid infiltrate and in two a marked polymorphonuclear leukocyte infiltrate was evident. Immunohistochemistry showed in all tumours that the spindle cells stained positively for myogenic markers (8 of 12 positive for desmin, 10 of 12 for alpha smooth muscle actin and 11 of 12 for HHF-35). CD68 was expressed by the histiocytic infiltrates. Many of these tumours were diagnosed initially as inflammatory malignant fibrous histiocytoma. We provide evidence that at least one subset of neoplasms, which would have been formerly classified under this rubric, in fact show smooth muscle differentiation. Further studies are required to investigate the possibility that other tumour types or lines of differentiation may be present within the category of so-called inflammatory malignant fibrous histiocytoma.

Adolescent↗

PubMed1995

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↗

PubMed1995

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↗

PubMed1995

Inflammatory pseudotumour of soft tissues: a clinicopathological and immunohistochemical analysis of 18 cases.

Pseudosarcomatous proliferation of myofibroblasts, fibroblasts and inflammatory cells have been reported in a wide variety of sites and are most commonly termed inflammatory pseudotumours. Despite increasing recognition, the occurrence of inflammatory pseudotumour in somatic soft tissue is poorly documented, such that these lesions are commonly mistaken for a variety of benign and malignant neoplasms. This report documents our experience of 18 cases of soft tissue inflammatory pseudotumour. All arose in adults (median age 54.5 years; range 28-83 years) and showed no sex predilection. Anatomical location was varied but the head and neck region and abdominal cavity were most common. They displayed a spectrum of histological appearances but all were characterized, to a greater or lesser extent, by an admixture of myofibroblasts and fibroblasts, most commonly arranged in short interwoven fascicles, together with a polymorphic inflammatory cell component, consisting principally of lymphocytes and plasma cells. In some cases xanthoma cells were prominent. Simple surgical excision appeared to be curative. The importance of recognizing the presence of a wide clinicopathological spectrum is emphasized and the differential diagnosis, especially from fibrohistiocytic neoplasms or Hodgkin's disease, is discussed.

Adult↗

PubMed1995

Monosomy 22 in a malignant peripheral nerve sheath tumour of the kidney in childhood: a genetic link with other malignant paediatric renal neoplasms?

A recurrent malignant spindle cell neoplasm of the kidney, occurring in a 11-year-old girl and corresponding to a malignant peripheral nerve sheath tumour is reported. The neurogenic differentiation was substantiated by the presence of PGP 9.5 neurofilament and S-100 protein positivity and by the ultrastructural features. Cytogenetic analysis revealed monosomy of chromosome 22 in the tumour while the constitutional karyotype was normal. Primary malignant peripheral nerve sheath tumour of the kidney is extremely rare and should, on morphology, be differentiated from stromal predominant Wilms' tumour and clear cell sarcoma of kidney. Involvement of chromosome 22 has been described in a number of malignant renal tumours of childhood, such as Wilms' tumour (deletion), clear cell sarcoma (translocation), and rhabdoid tumour (deletion and translocation), thus suggesting common molecular mechanisms in pediatric malignant renal tumours.

Child↗

PubMed1995

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↗

PubMed1995

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↗

PubMed1995

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↗

PubMed1995

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↗

PubMed1995

Malignant fibrous histiocytoma: morphologic pattern or pathologic entity?

Since the concept of malignant fibrous histiocytoma (MFH) was introduced and subsequently popularized in the 1960's and 1970's, it has become widely regarded as the commonest soft-tissue sarcoma of adulthood. Although the initial notion that MFH was a true histiocytic tumor showing faculative fibroblastic differentiation has been disproved, and despite the lack of definable, reproducible diagnostic criteria and considerable immunophenotypic, ultrastructural and karyotypic heterogeneity, MFH is still accepted widely as a discrete clinicopathologic entity. On the other hand several recent studies have expressed considerable doubts about MFH, or at least pleomorphic MFH, as an "entity" and have suggested that it represents a common morphologic manifestation of a host of poorly differentiated sarcomas and, more rarely, other neoplasms. This article reviews the clinicopathologic features of MFH and its established variants in the context of this debate and considers the evidence for and against their continued acceptance as distinct entities or as a cohesive group. We conclude that the pleomorphic, giant cell and inflammatory variants each represent heterogeneous diagnostic groups which are hard to defend as cohesive entities, while the myxoid ("myxofibrosarcoma") and angiomatoid types are distinct, reproducible tumor types.

Desmin↗

PubMed1994

Relationship of DNA ploidy to histology and prognosis in rhabdomyosarcoma. Comparison of flow cytometry and image analysis.

BACKGROUND: Although DNA ploidy correlates with prognosis in certain childhood cancers, e.g., neuroblastoma, its significance in rhabdomyosarcoma (RMS) is unclear and controversial. METHODS: Ploidy by flow cytometry (FCM) and image analysis (IA) in 26 of 27 children with RMS (17 embryonal, 3 mixed embryonal/alveolar, 5 alveolar, 1 anaplastic, 1 ectomesenchymoma) and 4 adults with pleomorphic RMS were evaluated. Statistical comparisons were analyzed between DNA content and gender, age, localization, Intergroup Rhabdomyosarcoma Study (IRS) group, and histopathologic subtype. Survival analyses were performed by the Kaplan-Meier test using the approximate chi-square statistic for the log rank test. RESULTS: The concordance rate between FCM and IA was 26 of 30 (87%); FCM was not performed in one tumor. Image analysis was more sensitive than FCM in detecting aneuploidy. Furthermore, DNA content was associated significantly with histologic subtype (P = 0.031); embryonal histology commonly was hyperdiploid (mean, 1.44; median, 1.27), whereas alveolar histology usually was near-tetraploid (mean, 1.83; median, 1.95). All four adult patients with pleomorphic RMS were aneuploid, with one showing multiple DNA peaks. No correlation between DNA content and survival was observed in the children with RMS. However, IRS group (P = 0.011) and patient age (P = 0.036) were independent prognostic indicators significantly related to survival. All adult patients died of their disease. CONCLUSIONS: Although ploidy correlates with histologic subtype, DNA content is not significantly predictive of prognosis in patients with RMS. Age at diagnosis and IRS group are independent predictors of clinical outcome in children with RMS.

Adolescent↗

PubMed1994

Clustered organization of Krüppel zinc-finger genes at Xp11.23, flanking a translocation breakpoint at OATL1: a physical map with locus assignments for ZNF21, ZNF41, ZNF81, and ELK1.

The ZNF21, ZNF41, and ZNF81 genes encode Krüppel-type zinc-finger proteins (ZFPs) and have previously been mapped to chromosome Xp. Published data describing the clustering of ZFP genes on human autosomes led us to investigate the organization of ZNF21, ZNF41, and ZNF81 on the X chromosome. Rodent-human hybrid analysis sublocalized all three genes to Xp22.11-p11.23. ZNF21, ZNF41, and ZNF81 were then shown to segregate within a series of YACs (95 to 730 kb) containing known markers at Xp11.23, such that these YACs could be assembled into a contig spanning approximately 1.5 Mb of DNA. Southern analysis of intact YACs and YAC DNAs cut with rare-cutter restriction enzymes enabled us to establish the spatial organization of the ZFP gene cluster, the OATL1 pseudogene, the recurrent t(X;18) chromosome translocation breakpoint in synovial sarcoma, and the previously described cluster of ARAF1, SYN1, TIMP, and PFC genes. We have assigned the ETS-related gene ELK1 to a locus tightly linked to the PFC gene; the entire cluster of five genes is contained within a distance of 120 kb. ZNF41 maps to a 440-kb YAC spanning this region, while a more proximal cluster comprising the ZNF21 and ZNF81 genes lies 150 kb distal to the chromosome breakpoint associated with synovial sarcoma.

Base Sequence↗

PubMed1994

Malignant mesenchymomas of soft tissue associated with numerous osteoclast-like giant cells mimicking the so-called giant cell variant of "malignant fibrous histiocytoma".

Three cases of malignant mesenchymoma with numerous osteoclast-like giant cells, arising in deep soft tissue, and which mimicked the so-called giant cell variant of "malignant fibrous histiocytoma" have been studied. All three neoplasms arose in adults; two patients were male and one was female. Two tumours arose in the thigh, and one in the right shoulder. Two patients died within 2 years of the primary excision while the third is alive and well at 2.5 years. Histologically, one case showed leiomyosarcoma plus liposarcoma, one leiomyosarcoma plus osteosarcoma, and one tumour consisted of liposarcoma plus osteosarcoma; all components were assessed morphologically as high-grade malignant. All three cases showed prominent osteoclast-like giant cells in the leiomyosarcomatous or osteosarcomatous areas, thereby closely mimicking the phenotype of so-called giant cell variant of "malignant fibrous histiocytoma". We discuss briefly differences in soft tissue sarcomas demonstrating this distinctive osteoclast-rich phenotype.

Adult↗