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C D Fletcher

Publications and source records attributed to C D Fletcher.

At least 181 records · Page 10Linked to original sources
PubMed1994

[Primary primitive neuroectodermal tumor of the kidney in an adult. Clinico-pathologic and immunohistochemical case report].

We report a case of a primary renal primitive neuroectodermal tumour in a 24-year-old man associated with multiple pulmonary metastases. Histologically, the bulk of the kidney was replaced by a small round-cell tumour with numerous true Homer-Wright rosettes and perivascular pseudorosettes; wide-spread vascular invasion was noted. There was no evidence at autopsy of a primary tumour elsewhere. Immunohistochemically, the tumour cells stained strongly positive for O-13, a monoclonal antibody, which recognizes a recently described cell membrane glycoprotein (p30/32MIC2), more weakly for NSE and at least focally for PGP 9.5; the tumour did not stain for other neural markers, cytokeratin, leucocyte common antigen, or desmin. The differential diagnosis of small round-cell tumours in this location and the relation of primitive neuroectodermal tumours and Ewing's sarcoma are discussed.

Adult↗
PubMed1994

[The histological features of local recurrences of soft tissue sarcomas].

Local recurrence is a well-recognised problem in soft tissue sarcomas, especially at difficult anatomical locations or after inadequate surgery. It is logical to assume that such recurrence will have an adverse effect on prognosis. In most cases the histological appearance of the recurrence is very similar to that of the primary neoplasm, in view of the fact that recurrence is most common in high-grade (poorly differentiated) sarcomas. However, in some cases, the appearance may change in one of three ways: (1) Gradual progression in grade. This phenomenon is seen most often in leiomyosarcoma or myxofibrosarcoma, in which the tumour shows progressive loss of differentiation and there is increasing risk of metastasis; (2) Abrupt change to a higher grade. This phenomenon, known as dedifferentiation, is commonest (among soft tissue lesions) in liposarcoma and is characterised usually by the emergence of an "MFH-like" pattern and an increased risk of metastasis; (3) Acquisition of differentiation. Some round cell sarcomas in children become better differentiated after chemotherapy, and some dedifferentiated adult sarcomas may revert to their well-differentiated form; occasionally the appearance of greater differentiation reflects sampling error in the primary tumour. Pathologists should be aware that significant morphological changes may occur in recurrent soft tissue sarcomas and, in analysing and diagnosing such lesions, they should always review material from the primary tumour.

Cell Differentiation↗
PubMed1994

[Vascular tumors of the skin and soft tissue. Overview of newly characterized entities and variants].

This review summarizes vascular tumours of skin and soft tissues that have been characterised in recent years. Although most of them are very rare, knowledge about their reproducible clinicopathological features is important to avoid diagnostic pitfalls. These lesions include: bacillary angiomatosis, a vasoproliferative, pseudoneoplastic infection of immunocompromised patients caused by Rochalimaea henselae; tufted angioma, a variant of lobular capillary haemangioma characterised by a "cannon-ball" distribution of multiple lobules composed of packed capillaries and pericytes; microvenular haemangioma, a cutaneous haemangioma composed of thin-walled and irregularly branching blood vessels which dissect dermal collagen; sinusoidal haemangioma, a distinctive variant of cavernous haemangioma which may be located in the subcutaneous breast tissue and then may be confused with well-differentiated angiosarcoma; "hobnail haemangioma" (targetoid haemosiderotic haemangioma), a benign vascular tumour with a distinctive clinical targetoid appearance and a hobnail cytomorphology of the prominent endothelial tumour cells; retiform haemangioendothelioma, a very recently characterised low-grade angiosarcoma occurring most commonly in the extremities of adolescents which is characterised by arborising blood vessels arranged in a retiform pattern and lined by hobnail-like prominent endothelial cells; Kaposi-like infantile haemangioendothelioma, a borderline malignant tumour of infants mimicking Kaposi's sarcoma histologically; epithelioid angiosarcoma, a highly aggressive tumour in the spectrum of epithelioid vascular lesions which stains positively for endothelial and epithelial immunohistological markers; benign lymph-angioendothelioma (progressive lymphangioma), a benign, slowly growing macule or plaque which has to be distinguished from well-differentiated angiosarcoma and Kaposi's sarcoma; and lymphangiomatosis of the limbs, a poorly recognised angiomatosis occurring in young patients and limited mainly to the limbs with a favourable prognosis.

Connective Tissue↗
PubMed1994

Effects of tibolone on lipoprotein(a) and HDL subfractions.

OBJECTIVE: To determine the effects of tibolone, a synthetic steroid used to alleviate climacteric symptoms and prevent osteoporosis, on lipoprotein metabolism, with particular reference to lipoprotein(a) levels and HDL subfraction profiles. DESIGN: Thirty nine postmenopausal women were treated with tibolone (Livial) 2.5 mg/day for 6 months and fasting serum lipoprotein levels were estimated at 0, 2, 4 and 6 months. RESULTS: Lipoprotein(a) levels were reduced significantly over the 6 months from a median level of 245 (range < 60-780) mg/l to 152 (range < 60-530) mg/l, a reduction of 39% in the median level. A decrease was observed in approximately two thirds of the women. Reductions were noted in all 6 subjects whose pretreatment levels were high, although concentrations remained at a level associated with increased risk in all but one. There were significant decreases in triglycerides and VLDL cholesterol and no significant change in LDL cholesterol. There was a significant reduction of 18% in HDL cholesterol and a 26% reduction in the HDL2-HDL3 ratio. CONCLUSION: The reduction in lipoprotein(a) levels may have a beneficial effect on cardiovascular risk, which could go some way towards balancing the potentially adverse effect on the cardiovascular system caused by the reduction in HDL cholesterol.

Adult↗
PubMed1994

Abnormalities of the p53 MDM2 and DCC genes in human leiomyosarcomas.

In this study we have screened a series of 29 primary leiomyosarcomas for abnormalities of both the p53 gene and the MDM2 gene, which encodes a p53-associated protein. SSCP (single-strand conformation polymorphism) analysis and direct sequencing of polymerase chain reaction (PCR)-amplified DNA were used to establish that 6/29 tumours possessed point mutations of the p53 gene. Using a monoclonal antibody that recognises the p53 protein in immunohistochemical staining experiments, we observed overexpression of the p53 protein in five of the six tumours containing point mutations in the p53 gene. Southern analysis of tumour DNA revealed that 2/29 tumours demonstrated amplification of the MDM2 gene. When considered together, these results indicate that alterations in both the p53 gene and MDM2 gene are important in the development of a significant minority of leiomyosarcomas. In addition, we have demonstrated a significant association between the presence of abnormalities of the p53 gene or MDM2 genes in leiomyosarcomas and a more advanced clinicopathological stage (P = 0.03). We have also examined the role of the DCC tumour-suppressor gene in the development of human soft-tissue tumours in a variety of histological types. Except for evidence of a rearrangement in a single leiomyosarcoma cell line, SK-UT-1, we have found no direct evidence to support a role for mutation of the gene in the development of human soft-tissue tumours.

Adult↗
PubMed1994

Fibroepithelial tumor of the breast with digital fibroma-like inclusions in the stromal component. Case report with immunocytochemical and ultrastructural analysis.

A case of fibroepithelial tumor of the breast in a 34-year-old woman, showing digital fibroma-like inclusions in the stromal component is presented. Morphological, immunocytochemical, and ultrastructural findings indicate that the peculiar eosinophilic intracytoplasmic inclusions observed may represent tightly packed actin filaments. Although they are more frequently detected within digital fibrous proliferations of infancy, their rare occurrence at either unusual site or in adulthood has been reported. Similar inclusions have also been rarely observed in intranodal myofibroblastoma and in benign leiomyomas. These findings suggest that these inclusions may be the result of some metabolic or organisational abnormality shared by neoplastic actin-rich cells. Myofibroblastic and smooth muscle lesions are probably the commonest to show this defect.

Actins↗
PubMed1994

Leiomyoma of deep soft tissue. Clinicopathologic analysis of a series.

Leiomyomas of deep soft tissue are extremely rare and, to our knowledge, have never been adequately characterized either histologically or clinically. We report 11 such cases, most often arising in deep subcutis or skeletal muscle. The lesions were equally distributed among males (six cases) and females (five cases); age at presentation ranged from 14 to 62 years (mean, 37 years; median, 35 years). The extremities represented the single most common site (five cases). Characteristic morphologic features included well-defined circumscription with a fibrous pseudocapsule, myxohyaline stromal degeneration, and intersecting fascicles of spindle cells with mostly uniform, round-ended, elongated nuclei and tapering, eosinophilic cytoplasm. Dystrophic calcification was identified in four cases; degenerative nuclear changes, similar to those in ancient schwannoma, were present in three cases. Two neoplasms showed multiple necrobiotic granuloma-like nodules resembling giant rosettes. Mitotic figures were found in only four cases and were scarce, never exceeding one mitotic figure per 50 high-power fields. Immunohistochemically, all cases showed desmin positivity. Clinical follow-up (median, 4.5 years), available for nine cases, revealed no evidence of local recurrence or distant metastasis. As with all smooth-muscle cell neoplasms, meticulous attention to the presence of significant mitotic activity and suppurative tumor necrosis is essential because they suggest potential malignant behavior.

Adolescent↗
PubMed1994

Spindle cell liposarcoma, a hitherto unrecognized variant of liposarcoma. Analysis of six cases.

A series of six cases of a previously unrecognized variant of liposarcoma characterized by a prominent spindle cell component is reported herein. Clinically, all of the tumors arose in adults and developed around the shoulder girdle or upper limbs; all but one arose in subcutaneous tissue. Three patients developed multiple local recurrences over a period of 4-20 years. Recurrences in one case were purely lipoma-like. Following dedifferentiation in a recurrence, one patient developed distant metastases and eventually died, 46 months after the primary excision. Grossly, these lesions are characterized by multinodularity, and microscopically they show a relatively bland spindle cell proliferation arranged in fascicles and whorls and set in a variably myxoid stroma. The spindle cell areas are accompanied by an adipocytic component, which exhibits the morphologic features required for inclusion in the well-differentiated liposarcoma-atypical lipoma group, including definite lipoblasts. Main differential diagnoses include benign lesions such as spindle cell lipoma and diffuse neurofibroma, as well as dermatofibrosarcoma protuberans and other malignancies such as sclerosing liposarcoma, low-grade myxofibrosarcoma, low-grade malignant peripheral nerve sheath tumor, and low-grade fibromyxoid sarcoma. In view of their distinctive histologic appearance, and because aggressive clinical behavior was observed despite their superficial location, we propose that these lesions be regarded as spindle cell variants of well-differentiated liposarcoma.

Adult↗
PubMed1994

Infantile hemangiopericytoma versus infantile myofibromatosis. Study of a series suggesting a continuous spectrum of infantile myofibroblastic lesions.

The clinicopathologic features of 11 tumors, originally diagnosed as infantile hemangiopericytomas and with a spectrum of morphologic findings, are described. The age of the patients ranged from 6 days to 7 years; seven patients were younger than 1 year (mean, 2.25 years; median, 10 months); six were boys and five were girls. Three neoplasms were situated in skin or subcutis and seven in deep soft tissue; in one case the depth was unstated. Seven lesions arose in the lower limbs, and one each in the lumbar region, clitoris, chest wall, and soft tissue of the zygomatic region. One patient later was found to have two additional dermal tumors, one each on the anterior abdominal wall and the chest wall. Follow-up information in eight patients revealed local recurrence 12 years later in one case only. Histologically, all tumors showed distinctive features of infantile hemangiopericytoma, including immature cytology, multilobulated growth pattern, focal necrosis, and mitotic activity in varying degrees. Vascular invasion was noted in seven cases. Additionally, a second tumor cell component, composed of spindle-shaped myofibroblastic cells forming fascicles and micronodules, was evident at least focally. Both the spindle cells and more primitive round cells were positive for alpha-smooth muscle actin. Both cellular components showed a haphazard zoning arrangement. We discuss the clinicopathologic similarities between infantile hemangiopericytoma and infantile myofibromatosis and point out the differences between infantile and adult hemangiopericytoma. Our study suggests that there exists a broad spectrum of benign infantile myofibroblastic lesions containing an immature-appearing cellular component with a distinctive, hemangiopericytoma-like vascular pattern. Infantile myofibromatosis and so-called infantile hemangiopericytoma almost certainly represent different stages of maturation of the same (single) entity.

Child↗
PubMed1994

Dedifferentiated liposarcoma. Clinicopathologic analysis of 32 cases suggesting a better prognostic subgroup among pleomorphic sarcomas.

Dedifferentiated liposarcoma is uncommon, and only a small number of cases have been documented. We describe the clinicopathologic features in a series of 32 cases. All patients were adults (age range, 37-83 years; median, 67 years); 20 were men and 12 were women. Commonest site was the retroperitoneum (fifteen cases); six cases arose in the limbs, four in the paratesticular region, three in the peritoneal cavity, two on the trunk, and one each in the buttock and larynx. One primary tumor was subcutaneous. Thirty tumors arose de novo (i.e., combined with well-differentiated tumor in the primary lesion), while two developed in recurrences of a previously well-differentiated liposarcoma. The well-differentiated component was most often lipoma-like and typically there was a histologically abrupt transition to spindle celled nonlipogenic tumor. The dedifferentiated component most often resembled either storiform "malignant fibrous histiocytoma" ("MFH") with limited pleomorphism or myxofibrosarcoma (myxoid "MFH"); the latter pattern is rarely otherwise seen in the retroperitoneum. A small number of cases showed appearances reminiscent of myxoid embryonal rhabdomyosarcoma. An unusual feature in three cases was the occurrence of a discontinuous micronodular pattern of dedifferentiation. Average follow-up of 5.6 years (range, 3 months to 33 years) in 27 cases have revealed local recurrence in 14 patients and systemic metastases in only four patients. The primary sites of the metastasising cases were upper back, thigh, retroperitoneum, and paratesticular region. There have been only seven tumor-related deaths. Good prognosis in de novo dedifferentiated liposarcomas seems unrelated to the extent or morphologic pattern of dedifferentiation. However, high mitotic activity in the dedifferentiated component was associated with a more aggressive clinical course. Our study underlines that dedifferentiation in peripherally located or even subcutaneous liposarcomas does occur, albeit rarely, and that dedifferentiated liposarcomas of the limbs may metastasize. The results suggest that dedifferentiated liposarcomas, as a subgroup among the "MFH-like" sarcomas, have a better prognosis than pleomorphic sarcomas as a whole.

Adult↗
PubMed1994

Granular cell change in smooth muscle tumours of skin and soft tissue.

Nine smooth muscle tumours, arising at a variety of sites and showing granular cell change of their cytoplasm, have been studied morphologically and immunohistochemically. The age of the patients ranged from 6 to 78 years (median 42 years); seven patients were female. Two tumours each arose in the dermis or subcutaneous tissue while the other five cases were situated in deeper soft tissue. Three of the lesions arose in the lower limbs, two in the pelvis and one each in the regions of the elbow, shoulder, breast and buttock. Follow-up in eight patients was available and revealed local recurrence in three and pulmonary metastases in two cases. All cases showed at least focally the light microscopic features of a smooth muscle tumour and demonstrated moderate to strong positivity for alpha-smooth muscle actin. Five were also HHF-35 positive and three were desmin positive. Noteworthy was strong positivity for the 'melanoma associated' antigen NKI/C3 in all cases. Six cases stained also weakly positive for NSE, but all were S-100 protein negative. The former is not specific but is the most reliable marker of lesions showing granular cell change. Granular cytoplasmic change represents simply a cytological phenotype, apparently representing a characteristic metabolic alteration, not exclusively associated with Schwann cell tumours. Tumours containing granular cells are best classified according to their line of specific cellular differentiation if possible.

Actins↗
PubMed1994

Spindle cell lipoma--a pseudoangiomatous variant.

Five cases of an unusual pseudoangiomatous variant of spindle cell lipoma are presented. In keeping with more typical cases, these lesions occurred principally in the shoulder and neck regions of adult males. The lesions all had the features of typical spindle cell lipoma but, in addition, exhibited irregular and branching spaces with villiform connective tissue projections, giving a striking angiomatoid appearance. Although the pathogenesis is uncertain, this unusual histological pattern seems to be the result of myxoid degeneration and may lead to a mistaken diagnosis of a true vascular tumour or other non-lipomatous spindle cell lesion.

Adult↗
PubMed1994

Epithelioid benign fibrous histiocytoma of skin: clinico-pathological analysis of 20 cases of a poorly known variant.

Twenty new cases of epithelioid fibrous histiocytoma, a distinctive but poorly recognized variant of cutaneous benign fibrous histiocytoma are described. Twelve patients were male and eight were female. The age of the patients ranged from 7 to 80 years (median 40 years). Six lesion arose on the lower limb, five on the upper limb, three around the shoulder, two on the abdomen and one each on the eyelid, inner canthus and anal margin. In one case the age and site were not stated. All lesions presented as a solitary, polypoid or slightly raised cutaneous nodule, ranging in size from 0.5 cm to 2 cm in greatest diameter. Follow-up in 14 cases (mean 22.7 months) revealed local recurrence after 42 months in one case. Histologically, the more polypoid tumours were characterized by an epidermal collarette. In all lesions prominent polygonal or rounded epithelioid cells with abundant eosinophilic cytoplasm, a vesicular nucleus and small eosinophilic nucleoli accounted for at least 50% of the tumour cell population. Individual cells were separated by somewhat hyalinized collagen, containing prominent blood vessels and a sparse mononuclear inflammatory cell infiltrate. The edge of the lesions, especially those that were non-polypoid, often showed more typical features of ordinary fibrous histiocytoma. The main differential diagnosis is with other cutaneous epithelioid neoplasms, especially Spitz naevus.

Adult↗
PubMed1994

Perineurioma (storiform perineurial fibroma): clinico-pathological analysis of four cases.

Four cases of perineurioma (storiform perineurial fibroma) arising in the dermis, subcutis, or deep soft tissue have been studied. Two patients were female and two were male with ages ranging from 19 to 45 years. One lesion each arose on the chest wall, shoulder, neck, and elbow. Follow-up information in three patients revealed no recurrence. Histologically, the neoplasms were circumscribed but non-encapsulated lesions and were composed of spindle cells with elongated bipolar cytoplasmic processes, inconspicuous fusiform nuclei and well-defined palely eosinophilic cytoplasm. These cells were arranged in whorls or lamellar-like structures and often demonstrated a storiform growth pattern. In areas, the tumour cells appeared larger with more rounded nuclei. Immunohistochemically, most of the tumour cells stained positive for epithelial membrane antigen and vimentin, but failed to stain for S-100 protein, neurofilament, desmoplakin, and CD34. Ultrastructurally, two cases showed fusiform tumour cells with long, thin cell processes separated by abundant collagen bundles. Tumour cells were covered by discontinuous external lamina, showed many pinocytic vesicles and occasionally desmosome-like structures. The morphology and EMA immunopositivity of perineurioma are similar to meningioma, especially to cutaneous meningioma type II. We believe that perineurioma and meningioma are closely related, but morphologically distinguishable, neoplasms.

Adult↗
PubMed1994

Deciduoid peritoneal mesothelioma. An unusual phenotype affecting young females.

Two cases of malignant peritoneal mesothelioma are reported. These tumors affected young women and displayed an unusual histopathologic pattern that closely simulated exuberant, ectopic decidual reaction or at least a malignant counterpart thereof. The importance of the differential diagnosis from decidual reaction is emphasized because decidua-like mesothelioma appears to be a highly malignant neoplasm. The cause of this lesion is unknown; and, considering the young age of the patients and the failure to demonstrate hormone receptors in the neoplastic cells, it is unlikely that asbestos exposure or hormonal imbalance played any role in the development of the disease.

Adult↗
PubMed1994

Cellular benign fibrous histiocytoma. Clinicopathologic analysis of 74 cases of a distinctive variant of cutaneous fibrous histiocytoma with frequent recurrence.

We report seventy-four cases of a distinctive variant of cutaneous fibrous histiocytoma, which is often mistaken histologically for sarcoma and which carries a high local recurrence rate. These tumors appeared most commonly in young or middle-aged adults, with a predominance in men (male/female ratio 1.9:1). Anatomic distribution was wide, with cases occurring mainly in the upper limb/limb girdle (34%), lower limb/limb girdle (27%), and head and neck region (20%). Most lesions had been present for only a few months, and their sizes ranged from 0.5 cm to 2.5 cm in maximum diameter. Twelve (26%) of 46 cases with follow-up (mean duration 3 years) recurred locally, in one case twice. Distinctive histologic features were a commonly fascicular growth pattern, predominance of eosinophilic spindle cells with tapering nuclei, a moderate mitotic rate (mean three per 10 high-power fields), and frequent extension into the subcutaneous fat (33% of cases). In addition, all cases showed at least focal cytologic polymorphism (inflammatory cells, foam cells, giant cells), and 58% showed associated epidermal alterations in common with usual cutaneous fibrous histiocytomas. Nine cases (12%) showed foci of central necrosis. Immunohistochemical studies (ABC method) found only vimentin and very focal smooth muscle actin positivity. Tests for CD34, desmin, S-100, keratin, and Factor XIIIa were negative in all cases. These lesions should be distinguished from dermatofibrosarcoma protuberans and leiomyosarcoma, with which many of these cases were initially confused.

Adolescent↗
PubMed1994

Ultraviolet-induced p53 mutations in atypical fibroxanthoma.

Atypical fibroxanthoma (AFX) is an uncommon neoplasm of the superficial soft tissue occurring in actinically damaged skin of elderly patients. Sun-exposed skin also represents the main site of squamous and basal cell carcinomas and malignant melanoma, and a key role for ultraviolet (UV) radiation in their pathogenesis has long been suspected. UV-related mutations of the p53 gene have been identified in human skin cancers. To verify whether the pathogenesis of AFX is related to the effect of sunlight, p53 protein and gene status have been investigated in a series of 10 cases of AFX. Seven of 10 showed p53 immunoreactivity in most of the neoplastic cells. Molecular analysis of the p53 gene revealed an abnormal single strand conformation polymorphism pattern in all the p53 positive cases. Polymerase chain reaction direct sequencing revealed that all the mutations involved cytosine bases. Four cases showed C to T transitions (including two CC-TT double base substitutions) and two cases showed C to G transversion. All but one mutation took place at dipyrimidine sites. These findings provide the first objective evidence for the central role of UV radiation in the development of AFX and also represent the first in vivo demonstration of solar UV-induced mutations in a human mesenchymal neoplasm.

Base Sequence↗