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Biomedical subjects

C D Fletcher

Publications and source records attributed to C D Fletcher.

At least 199 records · Page 11Linked to original sources
PubMed1994

Leiomyosarcoma with prominent osteoclast-like giant cells. Analysis of eight cases closely mimicking the so-called giant cell variant of malignant fibrous histiocytoma.

Eight cases of leiomyosarcoma with osteoclast-like giant cells, arising in deep soft tissue, and that mimicked closely the "giant cell variant of malignant fibrous histiocytoma (MFH)," have been studied morphologically and immunohistochemically. The age of the patients ranged from 7 to 88 years (mean, 66.2 years; median, 74 years); five were female patients. Three lesions arose in the lower limbs, two in the buttock, and one each in the shoulder, chest wall, and the floor of the mouth. Follow-up in one case revealed a local recurrence and in two cases systemic metastases. All cases showed, at least focally, interwoven spindle cell fascicles, with the cytologic features of smooth muscle cells, as well as strong positivity for alpha-smooth-muscle actin, muscle actin, and desmin. The morphologically benign osteoclast-like giant cells expressed CD68 but failed to stain with myogenic markers. The association of leiomyosarcoma with prominent osteoclast-like giant cells is not as uncommon as generally believed, being evident in 8.7% of the deep-seated nonvisceral leiomyosarcomas that we have studied. These results provide good evidence for myogenic differentiation in at least a subset of those tumors with morphologic features currently classified as the giant cell variant of MFH. Considering that at least some other reported cases of giant cell MFH appear to be a variant of extraskeletal osteosarcoma, we would suggest that lesions with this distinctive pattern should be more carefully classified according to their apparent line of differentiation.

Aged↗
PubMed1994

Rhabdomyosarcoma in adults.

Rhabdomyosarcomas occur in adults in one of two forms; as sporadic cases of the juvenile histological types and more commonly, if controversially, as the major adult form, pleomorphic rhabdomyosarcoma. This review documents the historical background to the fluctuating diagnostic popularity of pleomorphic rhabdomyosarcoma, together with a presentation of its defining clinicopathologic characteristics, and presents the clinicopathologic features of the juvenile types as they occur in adults. The concept of pleomorphic rhabdomyosarcoma as a distinct clinicopathologic entity, presenting as an aggressive, predominantly spindle-cell tumor arising in the skeletal musculature of middle-aged adults and defined by the presence of large, pleomorphic tumor cells, which show, at least focally, immunophenotypic or ultrastructural sarcomeric muscle differentiation, is discussed and supported.

Adult↗
PubMed1994

Retiform hemangioendothelioma. A distinctive form of low-grade angiosarcoma delineated in a series of 15 cases.

Fifteen cases of a distinctive type of low-grade angiosarcoma of the skin are described. Most tumors presented in the second to fourth decades of life, the youngest patient being 9 years old and the oldest 78 (mean age, 36 years). There was no sex predilection. Six tumors arose on the lower limb, four on the upper limb, three on the trunk, and one each on the penis and the scalp. One case arose in the setting of chronic lymphedema and another following radiotherapy for carcinoma of the uterine cervix. Distinctive morphologic features were the presence of long arborizing blood vessels arranged in a retiform pattern (reminiscent of normal rete testis) lined by monomorphic hobnail endothelial cells, a very prominent lymphocytic infiltrate in most cases, and the focal presence of papillae with hyaline collagenous cores, similar to those seen in malignant endovascular papillary angioendothelioma (Dabska's tumor). With a median follow-up of 7.25 years in 14 cases, retiform hemangioendothelioma has proved to be a low-grade neoplasm that recurs frequently but has a very low metastatic rate. The single regional lymph node metastasis in this series was from a case with a biphasic pattern in which only the spindle cell component was represented in the metastasis. There have been no tumor-related deaths, underlining the importance of accurate distinction from conventional angiosarcoma. This distinction is facilitated principally by the absence of dissection between individual collagen bundles and the absence of endothelial atypia or mitotic activity. The precise relationship between retiform hemangioendothelioma and Dabska's tumor is uncertain, possibly because cases of the latter may not be homogeneous.

Adolescent↗
PubMed1993

Nasopharyngeal angiofibroma: an immunohistochemical study of 32 cases.

Thirty-two cases of nasopharyngeal angiofibroma, including 2 recurrences, all of which had been excised from males between 7 and 25 years, were subjected to systematic immunohistochemical study. Most of the tumour vessels, which lacked elastic laminae, were characterized by vascular walls of irregular thickness and variable muscle content. In places endothelial cells were only separated from the stroma by a single attenuated layer of contractile cells, whereas elsewhere the same vessel walls showed pad-like thickenings of their muscle coat. All cells of the vessel walls showed immunoreactivity for vimentin and smooth muscle actin, whereas desmin-positive cells were present only in small numbers in some vessels, generally those with thicker muscle coats. The stromal cells were decorated by vimentin antibodies only; however, in some more fibrotic hyaline areas the stromal cells displayed also reactivity for smooth muscle actin. In most cases S-100 protein-staining disclosed many nerves, and this accentuated their parital distortion by tumour tissue. Our findings provide an extended insight to the morphology of angiofibromas at this site, particularly highlighting the irregularity of their vascular walls, which, taken together with the lack of elastic laminae and elastic stromal fibres, can be held responsible for the typical pronounced tendency for haemorrhage in these lesions.

Adolescent↗
PubMed1993

Synovial metaplasia of the skin.

We present two female patients, aged 15 and 45 years, with synovial metaplasia of the skin. Both lesions, localized in the knee and hand respectively, arose after preceding local trauma. Case 1 had intradermal irregular cystic spaces in the adjacent myxoid stroma of which large polygonal eosinophilic cells were found. In contrast, case 2 was characterized by a longitudinal space within the lower dermis and subcutis which was lined by a membrane similar to hyperplastic synovium. The cells of the membrane showed an eosinophilic spindle shaped cytoplasm with processes towards the lumen. In both cases the eosinophilic cells, strongly suggestive of fibroblasts, showed staining for vimentin only, whereas no reactivity could be obtained with antibodies to actin, desmin, S-100 protein, Factor VIII related antigen, cytokeratin, epithelial membrane antigen, carcinoembryonic antigen and CD 68. The absence of CD 68 positivity differs from that seen in normal and hyperplastic synovium. Delayed wound healing around a nidus seems the most likely cause of the change.

Adolescent↗
PubMed1993

Rhabdomyosarcomas with primary presentation in the skin.

Five primary and two metastatic rhabdomyosarcomas (RMS) with primary presentation in the skin were studied by conventional light microscopy and immunohistochemistry. These cases account for only 0.7% of the 682 cases of RMS collected at two large institutions with a main interest in soft tissue tumors. All but one tumor, which was an embryonal RMS, corresponded to the alveolar subtype. The myogenic nature of the tumor cells was supported by the immunophenotype including positive reactions for vimentin, desmin, and muscle actin. Clinical findings included a male predominance, young age of the patients and the location of all primary cutaneous RMS in the face. One of the two metastatic RMS presented at birth with a clinical picture highly suggestive of congenital metastatic neuroblastoma, notably because of a 100-fold amplification of the N-myc copy number. Thus, this case illustrates again that an amplification of the N-myc oncogene is not restricted to neuroblastoma, but may also occur in other tumor types.

Child↗
PubMed1993

True histiocytic lymphoma of small intestine. Analysis of two S-100 protein-positive cases with features of interdigitating reticulum cell sarcoma.

Two cases of true histiocytic lymphoma of the small intestine occurred in middle-aged patients, manifesting as tumors causing intestinal obstruction. One of the patients died of uncontrollable local and metastatic disease, 16 months after surgery and polychemotherapy, and the other patient is alive 12 months after surgery and chemotherapy. The histologic characteristics of the tumor cells, namely complex nuclear outlines and abundant variably eosinophilic cytoplasm, suggested histiocytic differentiation. Both cases had negative results for B-cell and T-cell markers but stained for the histiocytic markers lysozyme, CD68, and HLA-DR and had positive results for S-100 protein and vimentin. Acetone-fixed frozen sections of one case showed positive results for several histiocytic markers, including CD11c, CD14, CD33, CD68, and BerMac3 (unclustered monoclonal antibody). CD4, a T-cell antigen present in a subset of histiomonocytic cells, had positive results in the cytoplasm. The tumor cells had negative results for CD1a, CD15, and CD30. Immunoglobulin and T-cell receptor gene probes showed germline configuration in one case studied. These results indicate the tumors are true histiocytic lymphomas, which have immunophenotypic features of both ordinary histiocytes and interdigitating reticulum cells.

Antigens, CD↗
PubMed1993

Dermatomyofibroma: additional observations on a distinctive cutaneous myofibroblastic tumour with emphasis on differential diagnosis.

Following the very recent description of a benign plaque-like myofibroblastic tumour of the skin, known as dermatomyofibroma, we present four further cases, emphasizing its clinical features and its histological differential diagnosis. Three patients were adult females and one was a boy. Two of the lesions arose on the anterior abdominal wall, one on the shoulder, and one on the neck. Clinically, there was often close resemblance to a keloid. Follow-up revealed no evidence of recurrence after simple excision. Histologically, these were non-encapsulated but well-circumscribed, plaque-like lesions located in the reticular dermis, and composed of fascicles of monomorphic myofibroblasts, orientated parallel to the skin surface. Immunohistochemically, most of the tumour cells expressed alpha-smooth-muscle actin. The principal differential diagnosis is plaque-stage dermatofibrosarcoma protuberans. Other differential diagnoses include diffuse neurofibroma, dermatofibroma and other myofibroblastic skin tumours.

Actins↗
PubMed1993

p53 protein expression in non-neoplastic lesions and benign and malignant neoplasms of soft tissue.

Alterations of the p53 tumour suppressor gene, with consequent nuclear p53 protein accumulation, are among the most common genetic lesions in human neoplasms. In the present paper we show p53 immunoreactivity in 65% of malignant and 21% of intermediate malignancy soft tissue tumours, and in 48% of benign/reactive soft tissue lesions. p53 immunoreactivity of sarcomas can be interpreted as an indirect indication of a mutation of the corresponding p53 gene, suggesting that its alteration may have a role in their pathogenesis. Our data on p53 immunoreactivity in benign lesions of the soft tissues are among the first demonstrations of p53 over-expression in benign/reactive conditions. We cannot exclude mutations of the p53 gene in these cases, but it is difficult to sustain this hypothesis in reactive/pseudoneoplastic lesions. Alternatively p53 immunoreactivity in benign processes could be due to an increase in wild-type p53 as a result of different physiological mechanisms (cell type-specific p53 regulation, cell maturation, DNA repair). Our results do not indicate that immunohistochemical demonstration of p53 expression is a marker of malignancy in soft tissue tumours and therefore is of limited use in differential diagnosis. However, they suggest the need for further molecular genetic studies in order to elucidate the biological significance of the abnormal expression of p53 in benign soft tissue lesions.

Humans↗
PubMed1993

Ossifying fibromyxoid tumour of soft parts: immunohistochemical and ultrastructural analysis.

Ossifying fibromyxoid tumour of soft parts is a recently described benign neoplasm which usually presents in soft tissue. The histogenesis or pattern of differentiation is a source of controversy. Thirteen cases are reported herein. All arose in adults, principally on the upper trunk or head and neck region. None recurred. All but one tumour showed a shell of lamellar bone, laid down by reactive osteoblasts, at the tumour-host interface. The characteristic laciform, glomoid and fascicular patterns, usually in combination, necessitate differential diagnosis from chondroid, smooth muscle and neural tumours especially. Immunohistochemistry revealed positivity for S-100 protein in 10/12, desmin in 7/10 and smooth muscle actin in 4/8. Ultrastructural examination of four cases revealed prominent intermediate filaments, without myofilamentous organization, and a discontinuous external lamina. Immunoelectronmicroscopy localized desmin positivity to the filamentous meshwork. Differentiation therefore appears to take the form of an incomplete neural and smooth muscle phenotype, without evidence of complete maturation.

Actins↗
PubMed1993

Spindle-cell non-pleomorphic atypical fibroxanthoma: analysis of a series and delineation of a distinctive variant.

Atypical fibroxanthoma is a bizarre, cytologically malignant but usually clinically benign, lesion which typically arises in sun-damaged skin of the head and neck region in the elderly. Classically, its morphology is said to represent the dermal counterpart of pleomorphic malignant fibrous histiocytoma. We have identified 10 cases of a more monomorphic spindle-celled, fascicular variant which, paradoxically, was often mistaken for a clinically malignant lesion because it lacked the pleomorphism of conventional atypical fibroxanthoma. These tumours all arose in the head and neck region as polypoid lesions in the elderly. The tumours were confined to the dermis, often had an epidermal collarette, showed an eosinophilic fascicular morphology and were highly mitotic. All 10 were vimentin positive and five showed very focal actin positivity. Desmin, keratin and S-100 protein were negative in all cases. The clinical course was benign in all cases, justifying their accurate recognition. The principal differential diagnoses are spindle cell squamous carcinoma, spindle cell melanoma and leiomyosarcoma. Immunohistochemistry plays a key role in this distinction.

Aged↗
PubMed1993

Solitary myofibroma in adults: clinicopathological analysis of a series.

Solitary myofibroma is a recently described, benign neoplasm of superficial soft tissue, which represents the adult counterpart of infantile myofibromatosis and is poorly recognized. Eleven new cases are presented herein. The patients were mostly adults with ages ranging from 13-64 years. They presented with a solitary, usually painless nodule of variable duration in the skin or oral cavity. Histologically, each lesion had a biphasic pattern with spindle cells forming fascicular or whorled areas and rounded, more primitive cells arranged around small vessels, forming haemangiopericytoma-like areas. The characteristic zonation of infantile myofibromatosis was often less marked in adult lesions and there was a haphazard arrangement of the fascicular and pericytic areas in some cases. Hyalinization, especially of the peripheral spindle-celled areas, was frequent. Immunohistochemically, the spindle cells were desmin negative but muscle actin (HHF-35 and IA4) positive. The rounded cells were both desmin and actin negative. Electronmicroscopy confirmed the myofibroblastic/fibroblastic nature of tumour cells in two cases. Although vascular invasion was seen in two cases, solitary adult-type myofibroma pursues a benign clinical course.

Adolescent↗
PubMed1993

Lymphangiomyomatosis and angiomyolipoma: closely related entities characterized by hamartomatous proliferation of HMB-45-positive smooth muscle.

Angiomyolipoma is a hamartomatous condition which can occur as a component of the tuberous sclerosis complex. Lymphangiomyomatosis, another hamartomatous lesion occurring predominantly in the lungs, has long been suspected to be related to angiomyolipoma and tuberous sclerosis because of occasional clinical associations. We undertook this study to provide further support for the close relationship between these two entities. Five cases of lymphangiomyomatosis and 20 case of angiomyolipoma were retrieved for histological review and immunohistochemical studies. The antibodies used were anti-muscle specific actin (HHF-35), anti-desmin (D33) and anti-melanoma (HMB-45). Lesions featuring smooth muscle proliferation were used as controls. The proliferated smooth muscle cells in both lymphangiomyomatosis and angiomyolipoma were much plumper and paler or even clear, when compared with the deeply eosinophilic cytoplasm of the normal spindly smooth muscle cells and those of leiomyomas. Their nuclei were round to oval and pale rather than elongated and dark. Cells with bizarre nuclei were commoner in angiomyolipoma (18/20 cases) than lymphangiomyomatosis (1/5). In 12 cases of angiomyolipoma there were foci indistinguishable from lymphangiomyomatosis, i.e. plump spindle cells arranged in short fascicles around ramifying endothelium-lined spaces. All five cases of lymphangiomyomatosis stained for muscle-specific actin, desmin and HMB-45. For angiomyolipomas, the positivity rates for these markers were: 20/20, 17/20 and 18/20, respectively, including one case that was negative for both desmin and HMB-45. The various smooth muscle proliferations and tumours selected as controls were uniformly HMB-45 negative. The distinctive cytological features, morphological overlap and immunophenotypic profile all support a close relationship between lymphangiomyomatosis and angiomyolipoma, which probably represent different morphological manifestations of hamartomatous proliferation of a peculiar form of HMB-45-positive smooth muscle.

Adult↗