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Biomedical subjects

C D Fletcher

Publications and source records attributed to C D Fletcher.

At least 235 records · Page 13Linked to original sources

Pleomorphic malignant fibrous histiocytoma: fact or fiction? A critical reappraisal based on 159 tumors diagnosed as pleomorphic sarcoma.

Pleomorphic malignant fibrous histiocytoma (MFH) is regarded as the most common soft tissue sarcoma of adulthood, but no definable criteria exist for its diagnosis. Possibly its only distinctive feature is its apparent lack of specific differentiation. To determine the validity of pleomorphic MFH, 159 tumors diagnosed as pleomorphic sarcomas have been reassessed morphologically, immunohistochemically, and ultrastructurally, where possible. Of these 97 cases (63%) proved to be specific sarcomas other than MFH, 20 proved to be nonmesenchymal neoplasms, and 42 were unclassifiable (of which 21 were either small biopsies or subtotally necrotic). Only 13% of these cases were eligible for consideration as MFH, but these showed no reproducible histological differences from the other tumors studied, nor was this group morphologically consistent. These tumors showed no evidence of true monocyte/macrophage differentiation. It is postulated that pleomorphic MFH is a noncohesive heterogeneous group of poorly differentiated neoplasms, a term that has become a meaningless diagnosis of convenience. With sufficient effort, a specific line of differentiation can be identified in the majority of pleomorphic malignant soft tissue tumors; with advances in investigative technology, the proportion that remain unclassifiable is very likely to diminish further in the future.

Adolescent↗

Aggressive angiomyxoma. A report of four cases occurring in men.

Aggressive angiomyxoma is a distinctive, locally aggressive but nonmetastasizing soft tissue tumor of the pelvic soft tissues and perineum. This rare tumor occurs almost exclusively in adult women. We report four cases occurring in adult men, one each located in the scrotum, inguinal region, spermatic cord, and pelvis. The tumors were infiltrative, and were composed of fibromyxoid matrix sparsely populated by bland-looking spindled and stellate cells with delicate cytoplasmic processes. There were haphazardly scattered small and large blood vessels, some of which exhibited hypertrophy or hyalinization of the wall. Immunohistochemically, the stromal cells stained consistently for vimentin and variably for muscle-specific actin, but not alpha-smooth muscle actin, desmin, and S-100 protein. None of the four tumors recurred in follow-up times from 11 months to 6 years, although two previously reported cases in men recurred. This uncommon tumor occurring around the genital region in men merits wider recognition because of its potential for recurrence. It should be distinguished from benign tumors with low risk of recurrence on one hand, and from malignant myxoid tumors with metastatic potential on the other.

Adult↗

Sarcomatoid tumours of lymph nodes showing follicular dendritic cell differentiation.

Putative sarcomas of follicular dendritic cells are extremely uncommon and only small case numbers have been clearly documented. A major difficulty in their delineation has been the persistent controversy over the phenotype and ontogeny of normal follicular dendritic cells. Two new cases arising in adult females are presented herein, both of which had initially been mistaken for metastases from a true soft tissue sarcoma. Their morphology, immunophenotype, and ultrastructure (in one case) are described in order to aid their wider recognition. In the light of these findings, the nature and origin of follicular dendritic cells are discussed.

Adult↗

Malignant peripheral nerve sheath tumour with annulate lamellae mimicking pleomorphic malignant fibrous histiocytoma.

The nature and nosologic status of malignant fibrous histiocytoma (MFH), or at least its most common pleomorphic variant, are a matter of controversy and it is possible that this entity represents the shared morphologic phenotype of a range of other dedifferentiated neoplasms. An unusual case of malignant peripheral nerve sheath tumour which very closely mimicked pleomorphic MFH is presented. Its true nature was only disclosed by ultrastructural examination. A further interesting and previously unreported feature in tumours of this type was the presence of annulate lamellae in many of the tumour cells. This case adds weight to the assertion that the light microscopic features of pleomorphic MFH may not be specific.

Aged↗

Gastrointestinal stromal tumours: correlation of immunophenotype with clinicopathological features.

Stromal tumours of the gastrointestinal tract remain a persistent source of controversy with regard to both their proposed lines of differentiation and the difficulty in predicting their biological behaviour. We have examined 60 cases with a panel of seven antibodies directed at the identification of smooth muscular or neural differentiation. In our hands, 36 per cent of cases showed neural differentiation (although only 6.6 per cent expressed S-100 protein); 31 per cent appeared smooth muscular; 20 per cent manifested bidirectional differentiation; and 13 per cent were negative for all the markers used. Histological appearances do not reliably reflect immunophenotype. We have attempted to correlate immunophenotype with the site of the lesions and with their clinical behaviour. Mean follow-up of 5 years was obtained in 42 cases. Tumours with a neural phenotype have the best prognosis. Gastric tumours expressing both desmin and smooth muscle actin (in the absence of other markers) with up to 4 mitoses per 30 HPF behave in a benign fashion. Larger studies are required to substantiate the value of immunophenotyping this complex group of tumours.

Adult↗

Intravascular glomus tumour: a previously undescribed phenomenon.

We report the first case of an intravascular glomus tumour, which was located in the right forearm of a 40-year-old male. Microscopically the lesion originated from the wall of a vein and protruded into the lumen of the affected blood vessel. The tumour cells were characterized immunohistochemically by the presence of vimentin, actin and myosin. Within the tumour, small nerves, immunopositive for S-100 protein and neurofilaments, could be identified. Histogenetically, the tumour is thought to derive from intramural epithelioid cells of the venous part of an arteriovenous anastomosis.

Actins↗

Angiomatoid "malignant fibrous histiocytoma": an immunohistochemical study indicative of myoid differentiation.

Six cases of angiomatoid malignant fibrous histiocytoma (MFH), the rarest subtype of MFH, have been studied immunohistochemically using a broad panel of commercially available antisera in formalin-fixed, paraffin-embedded tissue in an attempt to define the pattern of differentiation shown by this unusual tumor. As has been reported in the more common types of MFH, no evidence of histiocytic differentiation was found. However, five cases strongly expressed desmin (DER-11) and two also expressed muscle actin (HHF 35). All tissues examined were negative for myoglobin and alpha-smooth muscle actin. These results provide good evidence for some sort of myogenic or possibly myofibroblastic differentiation in angiomatoid MFH. Given its clinicopathologically and immunohistochemically distinctive features, which are very different from the other variants of MFH, redesignation of angiomatoid MFH as a low-grade myogenic sarcoma of uncertain histogenesis is tentatively proposed. The new term angiomatoid myosarcoma is suggested.

Actins↗

Short-term changes in lipoproteins and apoproteins during cyclical oestrogen-progestogen replacement therapy.

Lipoproteins and apoproteins were measured weekly in a group of 18 post-menopausal women treated with a cyclical hormone replacement regimen comprising 28 days on conjugated equine oestrogens (0.625 mg/day) with the addition of norgestrel (0.15 mg/day) for the last 12 days of the cycle. There were no significant changes in total triglyceride, very low-density-lipoprotein (VLDL) cholesterol or high-density-lipoprotein (HDL) cholesterol levels. Low-density lipoprotein (LDL) and total cholesterol levels fell, the differences being significant after two weeks. The LDL/HDL cholesterol ratio also fell significantly over 1 week of treatment. There were no significant changes in either HDL2 or HDL3 cholesterol. The HDL2/HDL3 cholesterol ratio did, however, alter significantly, increasing during the oestrogen-only phase. Apart from this ratio, none of the parameters measured showed any significant differences as between the oestrogen-only phases and the oestrogen/norgestrel phases. There were no significant changes from baseline values in the levels of apoproteins AI, AII or B. The apoprotein AI/AII ratio was significantly increased, the levels being higher during the oestrogen phase of the cycle. There was no significant change in the apoprotein B/AI ratio. The apoprotein B/LDL cholesterol ratio showed a statistically significant increase after 4 weeks. There was no evidence of any cyclical changes. We conclude that the results of this study are generally favourable with regard to coronary heart disease risk but that the change in the apoprotein B/LDL ratio merits further investigation.

Apoproteins↗

Malignant mesenchymoma. Clinicopathologic analysis of a series with evidence of low-grade behaviour.

Malignant mesenchymoma is a rare soft tissue neoplasm which, by definition, shows at least two distinct types of frankly malignant mesenchymal differentiation in addition to any "undifferentiated" or "fibrosarcomatous" areas. It is generally regarded as a high-grade tumor. A series of nine new cases is presented in which all patients except one were adults. Four tumors arose in the retroperitoneum, three in the thigh. The only definable constituents were rhabdomyosarcoma (eight cases), liposarcoma (seven cases), and osteo/chondrosarcoma (five cases). On histologic grounds, at least one element in each case would normally be regarded as high grade. Of six cases with a median follow-up of 4.2 years, only one has died from tumor. One further case was an incidental postmortem finding. In contrast to most current opinion, these data suggest that malignant mesenchymoma is not as aggressive as the histology would imply.

Adult↗

Epithelioid angiosarcoma of deep soft tissue: a distinctive tumor readily mistaken for an epithelial neoplasm.

We report eight cases of epithelioid angiosarcoma arising in deep, usually intramuscular soft tissue. All the patients were men (mean age, 58). All the lesions arose in a limb or limb girdle. Cardinal morphologic features were the diffuse, sheetlike growth pattern, with only focally apparent vascular differentiation, and epithelioid tumor cells with a degree of intracytoplasmic vacuolation/lumen formation. Immunohistochemically, all eight cases coexpressed keratin as well as endothelial markers. In three cases, endothelial differentiation was confirmed ultrastructurally. Clinically, deep-seated epithelioid angiosarcomas are high-grade neoplasms that rapidly develop metastases. These findings expand the range of recognized epithelioid endothelial tumors and provide further evidence of keratin expression by such lesions. The presence of intracytoplasmic lumina/vacuoles (sometimes containing red blood cells) combined with the characteristic reticulin pattern and striking positivity for Factor VIII-RAg provide the clearest means of distinction from an epithelial metastasis.

Adult↗

Intramuscular angioma: a clinicopathological analysis of 74 cases.

We have studied 74 benign intramuscular angiomas in order to try and correlate clinical behaviour with histological appearances. The purpose was to find means of predicting those which would recur. Mean age at presentation was 17.6 years and 85% of the cases presented before age 30. The male: female ratio was 1.4:1. Anatomical distribution was 32% lower limb, 27% head/neck, 24% upper limb and 17% trunk. Reliable histological subclassification proved impossible since almost all lesions were of mixed type, albeit often with a single predominant vessel type--of which venous (42%) was the most common. Over 90% of the lesions contained a variably prominent adipocytic component. More than 50% of patients suffered local recurrence. Neither predominant vessel type nor anatomical localization correlated with recurrence, which was always due to incomplete excision.

Adolescent↗

Heterotopic glial nodules: a light microscopic and immunohistochemical study.

The clinical, light microscopic and immunohistochemical features of 14 heterotopic glial nodules are described. In keeping with previous experience, most cases were located around the nose and had been present since birth. However, several lesions presented as cutaneous nodules elsewhere and, in some, presentation was delayed into childhood or even adulthood. The histological diagnosis is usually uncomplicated, but we draw attention to a variant with a markedly sclerosed stroma in which the glial cells are relatively inconspicuous. Such lesions tend to be found in older subjects and can cause problems in diagnosis. We emphasize the value of immunohistochemical demonstration of glial fibrillary acidic protein in the diagnosis of these lesions, especially in the sclerotic variant. Other immunohistochemical features include the presence of axons in most cases and cell bodies in some, emphasizing the mixed nature of these lesions. A meningeal component could not be demonstrated immunohistochemically, even at the edge of the lesions.

Child, Preschool↗

Spindle cell haemangioendothelioma: a clinicopathological and immunohistochemical study indicative of a non-neoplastic lesion.

Spindle cell haemangioendothelioma is an uncommon vascular lesion, of which 35 cases have been previously reported. A further 20 cases are reported herein. These lesions affected a wide age range in both sexes, and showed a predilection for the extremities. Twelve patients had multiple lesions and, in these cases, local progression over many years but no true recurrence was typical. None of the 20 patients developed metastases, but one later developed an angiosarcoma. Individual cases were associated with congenital lymphoedema. Klippel-Trenaunay syndrome and early-onset varicose veins. Histologically, in addition to the admixture of cavernous spaces and solid spindle cell/epithelioid cell areas, the presence both of irregularly distributed and perivascular smooth muscle cells and of malformed variably-sized vessels at the periphery of almost every lesion was noted in each case. Reticulin staining, immunohistochemistry and electronmicroscopy revealed the presence of primitive vessel formation and partial endothelial differentiation in the solid spindle cell areas. Combining these data with those from previously published series, it is suggested that spindle cell haemangioendothelioma is a non-neoplastic lesion (rather than a borderline malignancy as it is currently regarded) and that its development correlates with histological and/or clinical evidence of a malformed vasculature at the affected site.

Adolescent↗

Haemangiopericytomas: the prognostic value of immunohistochemical staining with a monoclonal antibody to proliferating cell nuclear antigen (PCNA).

Forty-two cases of haemangiopericytoma were studied retrospectively using immunohistochemical staining with PC10, a monoclonal antibody to PCNA. The percentage of tumour cells with positive staining for PCNA was found to correlate well with histological grading. Clinical follow-up data were available in 25 adults and showed no known deaths in 11 cases with a low proportion (less than 14%) of positive cells. Out of 14 cases with a high number (greater than or equal to 14%) of positive cells, seven patients are known to have died, two had metastases, and in a further two there have been multiple recurrences of tumour. DNA flow cytometry was performed on 26 cases but this showed no correlation with PC10 staining or clinical outcome. Staining with PC10 may be of particular value in the identification of patients at greatest risk of rapid tumour metastasis and early death.

Adolescent↗

Smooth muscle tumours of the external genitalia: clinicopathological analysis of a series.

Smooth muscle tumours of the external genitalia (vulva, scrotum and nipple) are uncommon and have received little attention in the literature. Given their purported close relationship to cutaneous (pilar) leiomyomatous lesions, we have studied 32 cases (18 vulva, 10 scrotum, four nipple) from 31 patients in order to compare clinicopathological features at the different sites. Only those in the nipple were comparable in size and histology to pilar leiomyomas. Vulval and scrotal tumours tended to be much larger and better circumscribed. Purely epithelioid lesions were only identified in the vulva (two cases) and at this site myxoid change and hyalinization were substantially more common. Almost all cases showed immunohistochemical evidence of muscle differentiation. On histological grounds, nine cases were classified as leiomyosarcoma (six scrotum, three vulva) but only one of the five with follow-up has led to the patient's death. With the exception of nipple lesions, which are particularly uncommon, we would not support the traditional inclusion of genital smooth muscle tumours under the general heading of cutaneous leiomyoma/sarcoma, as vulval and scrotal lesions are clinicopathologically quite different.

Adult↗

Recently characterized vascular tumours of skin and soft tissues.

This review summarizes the clinicopathological features of a number of vascular tumours that have been characterized only in recent years. These include: glomeruloid haemangioma, a multifocal vascular lesion associated with POEMS syndrome: Kaposi-like infantile haemangioendothelioma, a borderline malignant tumour occurring in the retroperitoneum of infants, mimicking Kaposi's sarcoma histologically; giant cell angioblastoma, characterized by proliferated vessels with a granuloma-like appearance; benign lymphangioendothelioma (progressive lymphangioma), slowly-growing macule or plaque over the trunk or limb, mimicking low-grade angiosarcoma histologically; targetoid haemosiderotic haemangioma, a benign lesion with a distinctive annular appearance and histologically overlapping with benign lymphangioendothelioma; spindle cell haemangioendothelioma, a lesion located mostly in the distal extremities, characterized by cavernous vascular spaces, spindle cells with interspersed narrow vascular channels and scattered plump vacuolated endothelial cells; acquired tufted angioma, characterized by 'cannon-ball' involvement of the dermis by lobules of pericyte-rich capillaries; sinusoidal haemangioma, a distinctive variant of cavernous haemangioma which may be confused with angiosarcoma; and epithelioid angiosarcoma, a highly aggressive tumour of deep soft tissue mimicking metastatic carcinoma and co-expressing endothelial and epithelial markers.

Diagnosis, Differential↗

Plexiform fibrohistiocytic tumour: clinicopathological, immunohistochemical and ultrastructural analysis in favour of a myofibroblastic lesion.

Plexiform fibrohistiocytic tumour is a recently described, seemingly benign neoplasm of superficial soft tissue which is poorly recognized and the differentiation pattern of which remains obscure. Fourteen new cases are presented here. These presented predominantly in the upper limb of infants and children, although the age-range was wide. A morphological spectrum depending on the relative proportions of the spindle cellular and nodular histiocyte-like components was evident. Immunohistochemical analysis revealed positivity of tumour cells in both components for smooth muscle actin, suggestive of myofibroblastic differentiation, as was borne out ultrastructurally in two cases. In addition, a minority of the histiocyte-like cells were also CD68 positive but negative for leucocyte common antigen, HLA-DR, Mac387 and lysozyme. In view of the ultrastructural and other immunohistochemical results, this is regarded as further evidence that the CD68 epitope recognized by KP-1 is not confined to cells of monocyte/macrophage or myeloid lineage. Plexiform fibrohistiocytic tumour appears to be a clinicopathologically distinctive myofibroblastic neoplasm which may warrant reclassification in due course.

Actins↗