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C D Fletcher

Publications and source records attributed to C D Fletcher.

At least 73 records · Page 4Linked to original sources
PubMed1999

Primary alveolar soft part sarcoma of bone.

AIMS: Alveolar soft part sarcoma is a distinct, rare soft tissue tumour occurring primarily within the skeletal muscles or musculofascial planes in young adults. Primary involvement of bone is extremely rare. We report on six patients with alveolar soft part sarcoma occurring primarily in bone. METHODS AND RESULTS: Thorough clinical and radiographic examinations were done to rule out any other primary site. The patients were four women and two men aged 17-35 years (mean, 24.5 years). The primary site of the tumour was the femur in three patients, the ilium in one and the fibula in two. In one of the patients with fibular involvement, the tibia was also involved by direct extension. Of the long bone lesions, three were centred in the metaphysis and one in the diaphysis. Radiographically, all of the lesions demonstrated an osteolytic pattern of bone destruction with ill-defined margins and a wide zone of transition between the lesion and adjacent normal bone. Microscopically, all tumours showed the typical histological pattern of alveolar soft part sarcoma. Diastase-resistant, periodic acid-Schiff-positive crystalline structures were identified within the cytoplasm and confirmed ultrastructurally. Immunohistochemically, a keratin stain was negative in all cases; there was positive staining for MyoD1 in the cytoplasm but not the nuclei. Distant metastasis developed in four patients; one died. CONCLUSION: Alveolar soft part sarcoma arising in bone is extraordinarily rare but should be considered in the differential diagnosis of metastatic hypernephroma in a young patient.

Adolescent↗
PubMed1999

Soft-tissue sarcomas: an update.

Despite their relative infrequency (which is often used as an excuse for poor treatment), soft-tissue sarcomas have been the focus of considerable interest and advances in recent years, mainly because of molecular genetic developments as well as evolution in their histological classification. In parallel, however, there remains no clear consensus regarding either the ideal biopsy technique (in this era of increasing outpatient management) or the best means of prognostication (particularly by histological grading). This review aims to discuss some of these recent developments and co-existent controversies. Aside from the understandable pursuit of modern biotechnological innovations, it seems that the most important goal remains the need to achieve more consistent primary surgical management of these tumours, preferably in specialist centres.

Biopsy↗
PubMed1999

Plexiform spitz nevus: an intradermal spitz nevus with plexiform growth pattern.

Two cases of a distinctive variant of Spitz (spindle and epithelioid cell) nevus are described. One lesion developed on the lower leg of a 17-year-old boy and the other lesion on the back of a 52-year-old man. The microscopic appearance was characterized by a plexiform arrangement of bundles and lobules of enlarged spindle to epithelioid melanocytes throughout the superficial and deep dermis. Intraepidermal melanocytic proliferation was unappreciated. Some lobules were circumscribed by a thin rim of compressed fibrous tissue. In both cases a myxoid stroma was present. The cells had abundant eosinophilic cytoplasm with well-defined borders. The nuclei were enlarged, consistently ovoid and vesicular, with small nucleoli. Both cases contained scattered multinucleate giant cells similar to those observed in classical form of Spitz nevi. No melanin pigment was detectable by light microscopy. No mitoses were observed in one case and a rare mitosis was present in the other. Tumor cells were strongly immunoreactive for S-100, but not for HMB-45, desmin, and actin. The differential diagnosis of this distinctive tumor includes desmoplastic/neurotropic melanoma, plexiform spindle cell nevus, cellular blue nevus, plexiform neurofibroma, and cellular neurothekeoma. The designation of "plexiform Spitz nevus" is chosen to emphasize its distinctive plexiform growth pattern.

Adolescent↗
PubMed1999

Hobnail hemangioma: a pseudomalignant vascular lesion with a reappraisal of targetoid hemosiderotic hemangioma.

The clinicopathologic features of 15 cutanous hemangiomas having a distinctive and frequently pseudomalignant morphologic appearance are presented. There were 5 male and 9 female patients, whose ages at diagnosis ranged from 11 to 58 years (median 30.5). An angiomatous/pigmented, nontargetoid, flat, or exophytic lesion of variable duration was the main presenting sign. The tumor sizes ranged from 0.4 cm to 2 cm (median 1 cm). The locations included the lower limb, particularly the thigh (8); the trunk, including the shoulder area (4); the head (1); the gingiva (1); and the tongue (1). One patient had two lesions; none had a concomitant vascular anomaly or was suspected to have HIV infection. Treatment consisted of excisional biopsy in all cases. Follow-up information on 10 patients (range 4-66 months; median 13 months) showed no recurrence. On microscopic examination, the lesion showed a biphasic pattern characterized by the presence of well-formed, dilated, vascular channels in superficial dermis and a collagen-dissecting, pseudoangiosarcomatous pattern as the lesion infiltrated deeper into the dermis. The lining endothelium consistently showed distinctive hobnail cytomorphology; although there were endoluminal stromal papillae, there was no endothelial multilayering or tufting. Cytologic atypia was minimal or absent, and there were no mitoses. In 3 cases, the morphologic features were reminiscent of retiform hemangioendothelioma. Immunohistochemistry performed in 8 cases showed variable reactivity of endothelial cells with CD31, CD34, Factor VIII-related antigen, and Ulex europaeus agglutinin-1 in all cases; smooth muscle actin-positive pericytes were observed focally around some of the abnormal vascular spaces. The above-described hemangiomatous lesions share many features with so-called targetoid hemosiderotic hemangioma (a clinically descriptive term), but show a variable, often minimal, amount of hemosiderin deposition. The histologically descriptive term hobnail hemangioma is proposed to designate these lesions. Hobnail hemangioma should be distinguished from well-differentiated angiosarcoma, patch-stage Kaposi's sarcoma, and retiform hemangioendothelioma, with which it may be confused.

Adolescent↗
PubMed1999

Leiomyosarcoma of soft tissue in children: clinicopathologic analysis of 20 cases.

Leiomyosarcoma in the pediatric age group is uncommon and incompletely characterized. A series of 20 primary leiomyosarcomas of soft tissue occurring in children younger than 16 years is presented. No significant gender predilection was observed (11 girls and 9 boys). Patient age ranged from 4 to 15 years (median, 12 years). Tumor size ranged from 0.5 to 13 cm (median, 2.5 cm); subcutaneous and deep locations were equally represented. Tumors were evenly distributed among the trunk (30%), head and neck (25%), lower limbs (25%), and upper limbs (20%). All lesions showed at least focally typical features of smooth muscle differentiation, principally in the form of fascicles of eosinophilic spindle cells with cigar-shaped nuclei. An unusual whorled growth pattern was seen in two cases. Morphologic variants including inflammatory leiomyosarcoma (one case), granular cell leiomyosarcoma (two cases), giant-cell rich leiomyosarcoma (two cases), and epithelioid leiomyosarcoma (one case) were seen. Dystrophic calcifications were present in two cases. Most lesions (85%) were low grade. Immunohistochemical staining showed positivity for alpha-smooth muscle actin in 89% of the cases, HHF-35 in 87%, and desmin in 61%. Positivity for cytokeratins, observed in 6 (43%) of 14 cases tested, was usually strong and was diffuse in two cases. Follow-up data, available in 15 (75%) patients (median duration, 49 months), showed late local recurrence in only two cases, one with progression to a higher grade lesion, and no metastasis. These results show that, although extremely rare, soft-tissue leiomyosarcomas do occur in children, in whom they usually present as small morphologically low-grade lesions that seem to behave in a relatively indolent fashion, although longer follow-up data are needed. Differential diagnosis in this setting includes infantile myofibromatosis, leiomyoma, monophasic synovial sarcoma, and spindle cell rhabdomyosarcoma.

Adolescent↗
PubMed1999

Superficial angiomyxoma: clinicopathologic analysis of a series of distinctive but poorly recognized cutaneous tumors with tendency for recurrence.

Despite being first described in 1988, superficial angiomyxoma is still a poorly recognized cutaneous tumor. Although its histologic features are distinctive, its existence seems not to be widely accepted. We analyzed the clinicopathologic and immunohistochemical features in a series of 39 cases. Twenty-five patients were males; age range was birth to 82 years (median, 45.5 years). Most cases presented as cutaneous papules, nodules, or polypoid lesions. Seventeen tumors arose on the trunk, 14 on the head and neck, and seven on the lower limbs. All cases were treated by local excision, and eight recurred locally. In four of the latter cases, there were two recurrences. Histologically, the lesions were dermal with variable involvement of the subcutis. Tumors were poorly circumscribed, but a focal lobular outline was always identified. Distinctive histologic features included extensive myxoid stroma, numerous small blood vessels, varying cellularity, acellular mucin pools, stellate or bipolar fibroblastic cells, muciphages, a sparse, mixed inflammatory cell infiltrate with notable neutrophils, and occasional plumper cells with eosinophilic cytoplasm. Cytologic atypia was mild at most, and mitotic figures were rare. In approximately 20% of cases, the primary lesion or its recurrence contained epithelial structures, including epidermoid cysts, thin strands of squamous epithelium, and small buds of basaloid cells. Immunohistochemically, tumor cells were negative for S-100 protein, smooth muscle actin, and pan-keratin. We support the concept of superficial angiomyxoma as a distinctive clinicopathologic entity that should be included in the differential diagnosis of other myxoid cutaneous tumors, including dermal nerve sheath myxoma, trichodiscoma and trichofolliculoma, and low-grade myxofibrosarcoma.

Adolescent↗
PubMed1999

Adults with Ewing's sarcoma/primitive neuroectodermal tumor: adverse effect of older age and primary extraosseous disease on outcome.

OBJECTIVE: To assess outcome and prognostic factors for survival of adults with Ewing's sarcoma/primitive neuroectodermal tumor (PNET). BACKGROUND: Ewing's sarcoma/PNET is a disease of childhood rarely seen in adults. Accordingly, there is a relative paucity of published literature pertaining to outcome for adults with this disease. METHODS: Between 1979 and 1996, 37 patients with newly diagnosed Ewing's sarcoma/PNET were evaluated and treated at the Adult Sarcoma Program at Dana-Farber Cancer Institute and Brigham & Women's Hospital. Twenty-six patients had localized disease at presentation and 11 had metastatic disease. All but two patients received multiagent chemotherapy. Local treatment consisted of surgery (7 patients), surgery and radiation therapy (19), radiation therapy (6), or no local treatment (5). Median follow-up for living patients was 100 months (range 8 to 199). RESULTS: The 5-year survival rate for the group overall was 37%+/-9%. The 5-year local control rate was 85%+/-7%. Significant favorable predictors for survival on univariate analysis included localized disease at presentation, primary origin in bone, primary size <8 cm, and a favorable objective response to chemotherapy. Patients with localized disease had a 5-year survival rate of 49%+/-11% compared with 0% for those with metastatic disease at presentation. Multivariate analysis showed three significant independent predictors for death: metastatic disease at presentation, primary origin in extraosseous tissue versus bone, and age 26 years or older. CONCLUSION: Adult patients with Ewing's sarcoma/PNET at highest risk for death are those who are older than 26 years and have metastatic disease or an extraosseous primary tumor. The development of novel therapies should target these high-risk groups.

Adolescent↗
PubMed1999

Long-term outcomes after function-sparing surgery without radiotherapy for soft tissue sarcoma of the extremities and trunk.

PURPOSE: To define the rate of local recurrence (LR) and identify prognostic factors for LR for patients with soft tissue sarcoma (STS) treated with function-sparing surgery (FSS) without radiotherapy (RT). PATIENTS AND METHODS: Between 1970 and 1994, 242 patients with STS of the trunk and extremity presented with primary localized disease, 74 of whom were treated with FSS without RT (31%). The median tumor size was 4 cm (range, 0.5 to 31 cm). There were 40 patients with grade 1 tumors and 34 with grade 2 and 3 tumors. Median follow-up was 126 months. RESULTS: The 10-year actuarial local control rate was 93% +/- 4%. Resection margin status was a significant predictor for LR. Patients with closest histologic resection margins of less than 1 cm had a 10-year local control rate of 87% +/- 6% compared with 100% for patients with closest histologic resection margins of >/= 1 cm (P =.04). There was no significant association between LR and tumor grade, size, site (truncal v extremity), or depth (superficial v deep). For all patients, the 10-year actuarial survival rate was 73% +/- 6%. CONCLUSION: The 7% LR rate after treatment of STS with FSS without RT reported herein is comparable to published rates following treatment where adjuvant RT is used. These results suggest there may be a select subset of patients with STS in whom carefully performed FSS may serve as definitive therapy and in whom adjuvant RT may not be necessary. However, further study is needed to carefully define this subset of patients and to identify the optimal surgical approach and technique for patients treated without RT.

Adult↗
PubMed1999

Epithelioid and spindle-celled leiomyosarcoma of the heart. Report of 2 cases and review of the literature.

BACKGROUND: Primary cardiac leiomyosarcomas are rare. Isolated reported cases and small series generally describe spindle-celled, high-grade tumors with poor short-term survival; however, the pathologic features of many of these tumors are incompletely documented. The authors report in detail the clinicopathologic features of 2 relatively low-grade epithelioid and spindle-celled primary cardiac leiomyosarcomas. METHODS: Cases 1 and 2 were studied using standard histochemical and immunohistochemical techniques, and case 1 was examined by electron microscopy. The literature was reviewed with regard to primary cardiac leiomyosarcomas. RESULTS: Both tumors showed epithelioid and spindle-celled areas. The tumor in case 1 was low grade, and the tumor in case 2 was predominately low grade with a high-grade focus. A review of 28 reported cases revealed a wide age range (mean, 43 years), equal male-to-female ratio, and a predilection for the left atrium (48%). Follow-up of reported cases with fewer than 5 mitoses per 10 high-power fields showed a mean survival of 22 months compared with a 9-month mean survival for all others. CONCLUSIONS: Short-term follow-up of reported cases of high-grade cardiac leiomyosarcoma suggests a poor prognosis. Long-term follow-up in our case 2, along with follow-up of reported cases that were histologically similar to our cases, suggests that cardiac leiomyosarcomas with low-grade features or mixed low- and high-grade features also have a poor overall long-term survival, with a high rate of local recurrence and systemic spread.

Adult↗
PubMed1999

Myxoid synovial sarcoma: an underappreciated morphologic subset.

Focal myxoid change is a well-recognized feature of synovial sarcoma, but the presence of a predominantly myxoid stroma is rare. We describe seven cases of myxoid synovial sarcoma in which marked myxoid change initially obscured the diagnosis, leading to confusion (principally with malignant peripheral nerve sheath tumor). The median age (20 yr) and tumor location (four lower extremity, two upper extremity, and one head and neck region) were similar to those found in typical synovial sarcoma. Histologically, five cases were monophasic spindle cell lesions with a lacy appearance in areas with a prominent Alcian blue-positive myxoid stroma. Each case had foci with more typical features of synovial sarcoma, including a fascicular growth pattern with a variably collagenized stroma, stromal mast cells, a hemangiopericytoma-like vascular pattern, and calcification. Two cases showed small foci of glandular (biphasic) differentiation. Immunohistochemically, all of the seven cases were positive for epithelial membrane antigen, four of six were positive for pan-keratin, three of six were positive for S-100, two of four were positive for CD99, and six of six were negative for desmin. Clinical follow-up in six cases ranged from 8 to 48 months (median, 21 mo). Local recurrence developed in three patients at 9, 20, and 24 months, respectively. In one of these three patients, lung metastases developed at 13 months, and the patient died of disseminated disease at 23 months. In another of the three patients, lung metastases developed at 27 months. Three patients had no evidence of disease at 8, 15, and 15 months. Our data are too limited to indicate any clinical differences between myxoid synovial sarcoma and conventional synovial sarcoma Recognition of this rare histologic variant of synovial sarcoma is important because it can easily be mistaken for other myxoid spindle cell neoplasms, potentially resulting in suboptimal therapy.

Adolescent↗
PubMed1999

Myxoid solitary fibrous tumor: a study of seven cases with emphasis on differential diagnosis.

Focal myxoid change is a well-recognized feature of solitary fibrous tumor (SFT), but to date, predominantly myxoid examples of SFT have not been reported. We describe seven cases of SFT in which stromal myxoid change affected 50% or more of the tumor examined, thus obscuring typical diagnostic features. Patients ranged in age from 35 to 68 years old (median, 45 yr), with an equal sex distribution. Tumor locations included pleura, orbit, and periparotid subcutaneous tissue, as well as four cases in deep soft tissue (two in the abdominal wall and one each in the chest wall and thigh). Myxoid areas were identified grossly in four cases. Histologically, the lesions were composed of bland spindle cells disposed haphazardly or with a lacy or reticulated appearance in a myxoid, richly vascularized stroma These myxoid areas were punctuated by small cellular aggregates in four cases, and areas showing diagnostic features of SFT were present in five of seven primary excision specimens. Atypical features suggestive of malignancy were not present in any of the cases. Immunohistochemically, all of the seven cases stained positively for CD34 and CD99 (013), and all were negative for smooth muscle actin, desmin, S-100 protein, epithelial membrane antigen, and pan-keratin. There were no recurrences or metastases reported in four patients with limited follow-up (median duration, 19 mo). Recognition of this uncommon morphologic subset of SFT is important because of possible confusion, particularly in small biopsy specimens, with a variety of myxoid spindle cell neoplasms with different biologic potential. These include low-grade fibromyxoid sarcoma, myxoid synovial sarcoma, malignant peripheral nerve sheath tumor, low-grade myxofibrosarcoma, myxoid liposarcoma, myxoid spindle cell lipoma, myxoid neurofibroma, and so-called "hemangiopericytoma."

12E7 Antigen↗
PubMed1999

Effects of tibolone on serum lipoprotein and apolipoprotein levels compared with a cyclical estrogen/progestogen regimen.

OBJECTIVE: The purpose of the study was to examine the effects of tibolone, a synthetic steroid that alleviates climacteric symptoms and prevents bone loss without inducing monthly bleeds, on lipoprotein cardiovascular risk markers and to compare the effects with those of a standard combined estrogen/progestogen preparation. DESIGN: Ninety-seven postmenopausal women were randomly allocated to receive either tibolone 2.5 mg/day or conjugated equine estrogens 0.625 mg/day with norgestrel 0.15 mg/day for 12 of each 28 days. Fasting serum levels of lipids, lipoproteins, and apolipoproteins (Apo) were monitored during 18 months of treatment. Women on the cyclical preparation had levels determined during both estrogen-only and combined phases. RESULTS: Tibolone caused reductions in triglycerides (33%, p < 0.001), very low density lipoprotein (VLDL) cholesterol (43%, p < 0.001), and high density lipoprotein (HDL) cholesterol (18%, p < 0.001). The HDL2/HDL3 ratio fell by 22% (p < 0.001). Levels of Apo AI and AII were reduced by 18 and 8%, respectively (p < 0.001). The combined preparation caused reductions in VLDL cholesterol (23%, p < 0.001) and low density lipoprotein cholesterol (15%, p < 0.001). There were small reductions in HDL3 cholesterol and in Apo AII and Apo B. All parameters, except for Apo AII and Apo B and lipoprotein (a) [Lp (a)], showed cyclical changes. Lp (a) levels were reduced significantly by both treatments. CONCLUSIONS: The cyclical preparation had potentially beneficial effects on LP risk markers. The reduction in HDL induced by tibolone constitutes a potentially adverse change, which may be offset by the substantial falls in triglycerides, VLDL cholesterol, and Lp (a).

Anabolic Agents↗
PubMed1999

Analysis of 35 cases of localized and diffuse tenosynovial giant cell tumor: a report from the Chromosomes and Morphology (CHAMP) study group.

The karyotypes of 44 specimens from 35 patients with localized (n = 19) or diffuse (n = 16) tenosynovial giant cell tumors were studied. The majority of cases in both categories (11 of 19 localized; 12 of 16 diffuse) displayed clonal chromosomal aberrations, with a complex karyotype in three cases and a simple chromosomal aberration in the others. No difference in the distribution of karyotypic abnormalities was found between the localized and diffuse form except for trisomies (usually of chromosomes 5 and/or 7), which were more frequent in the diffuse type. The short arm of chromosome 1 (1p11-13) was most frequently rearranged, with 7 of 11 localized and 7 of 12 diffuse lesions affected. These findings indicate that the localized and diffuse forms of tenosynovial giant cell tumor might represent two morphologic manifestations of the same entity. The high frequency of clonal chromosomal abnormalities, with a clustering of structural rearrangements to 1p11-13, suggests that this disease is most likely neoplastic in nature and paves the way to search for gene(s) that might be involved in its development.

Adolescent↗
PubMed1998

Comparison of chromosomal patterns with clinical features in 165 lipomas: a report of the CHAMP study group.

Soft tissue lipomatous tumors are morphologically heterogeneous. Various morphologic features are associated with specific chromosomal patterns and clinical features such as age, sex, and tumor site, location, and size. Simple lipomas are known to be karyotypically heterogeneous, but this has not been correlated with clinicopathological features. In 165 cases of solitary soft tissue lipoma, short-term cultures were analyzed cytogenetically. The karyotypes were divided into the following groups: normal karyotype; 12q13-15 aberrations; 6p rearrangements; 13q rearrangements, 8q11-13 aberrations; ring or giant marker chromosomes or both; other aberrations. The tumors were reexamined morphologically without knowledge of the karyotypic or clinical data. An abnormal chromosomal pattern was observed in 129 of 165 cases (78%): in 75 of 90 (83%) lipomas in the extremities and in 43 of 63 (68%) trunk wall lipomas. Chromosomal aberrations were present in 69 of 90 (77%) subcutaneous tumors and in 59 of 64 (80%) deep tumors. A normal karyotype was twice as frequent in tumors in patients under 30 years of age than in those from older individuals (6 of 16 vs. 30 of 149, 40% resp. 20%). Apart from the finding that normal karyotypes were more common in patients younger than 30 years, there was no significant association between cytogenetic pattern and patient sex or age or tumor localization, size, or depth. The pathogenetic basis and clinicopathologic relevance (if any) of the cytogenetic subtypes among benign lipomas remain unexplained.

Adolescent↗
PubMed1998

Cytogenetic analysis of 46 pleomorphic soft tissue sarcomas and correlation with morphologic and clinical features: a report of the CHAMP Study Group. Chromosomes and MorPhology.

With the aim of identifying objective cytogenetic-morphologic correlations, we evaluated 46 pleomorphic soft tissue sarcomas (mainly diagnosed originally as malignant fibrous histiocytomas) with clonal chromosome aberrations both cytogenetically and morphologically as part of an international collaborative study. By detailed histopathologic examination, most cases could be categorized into specific tumor types. Eight sarcomas were diagnosed as lipogenic (4 pleomorphic, 1 combined pleomorphic and myxoid/round cell, and 3 dedifferentiated liposarcomas), 19 as myogenic [11 leiomyosarcomas, 1 rhabdomyosarcoma, 4 myosarcomas not otherwise specified (NOS), and 3 probable myosarcomas NOS], 8 as myxofibrosarcomas, 1 as a malignant peripheral nerve sheath tumor, 1 as malignant mesenchymoma, 1 as extraskeletal osteosarcoma, I as sarcoma resembling proliferative fasciitis, and 7 as pleomorphic sarcomas NOS. In a three-grade system, 10 tumors were grade 2 and 36 were grade 3. The majority had highly complex karyotypes. A total of 24 recurrent abnormalities (defined by their presence in at least five cases) were detected: ring chromosomes, homogeneously staining regions (hsr) and/or double minute chromosomes (dmin), and structural rearrangement of 22 different chromosome bands or regions. The frequency and distribution of the recurrent karyotypic features were uneven. Grade 3 tumors displayed, on average, more aberrations per case than did grade 2 tumors. Nine of the selected abnormalities, including hsr/dmin and rearrangements of 19p13 and 19q13, were found only among the high-grade tumors. When the tumors were subdivided according to lineage of differentiation, the highest frequency of aberrations was seen in pleomorphic sarcomas NOS, followed by myxofibrosarcomas, myogenic sarcomas, and lipogenic sarcomas. None of the selected rearrangements was, however, specific for any of these subgroups. The sole consistent cytogenetic-morphologic association was that all three dedifferentiated liposarcomas had multiple abnormal clones, at least one of which contained supernumerary ring chromosomes. Due mainly to karyotype complexity, it therefore seems unlikely that cytogenetic analysis can assist in the differential diagnostic subclassification of pleomorphic sarcomas, nor was there any clear-cut indication that the karyotypic picture could be used to predict clinical outcome. Although the mean number of recurrent chromosome aberrations was almost twice as high in sarcomas that gave rise to metastases as among those that did not, no particular aberration was restricted to either of the two subgroups.

Adult↗
PubMed1998

Long-term effects of continuous combined HRT on bone turnover and lipid metabolism in postmenopausal women.

This study was undertaken to investigate the effect of 10 years of hormone replacement therapy (HRT) on bone turnover and lipid metabolism in postmenopausal women. The single-centre trial was initiated as a 1-year, double-masked, randomized, parallel-group study of continuous combined HRT with 2 mg 17 beta-estradiol and 1 mg norethisterone acetate administered once daily with or without 1 mg estriol. Following preliminary results which showed no difference between the addition and omission of estriol, patients continued on an open-label extension phase of continuous combined HRT without estriol for a further 9 years. Of the 52 women who entered the original double-masked study, 32 entered the open-label extension phase. The 10-year analysis was based on 27 patients. Major increases in bone mineral density (BMD) of the lumbar spine were seen during the first 3 years of treatment, remaining statistically significant compared with baseline at all visits throughout the 10-year follow-up (p < or = 0.025). Statistical modelling confirmed that there were no decreases in BMD after these initial increases. BMD remained 5.5% higher than baseline values after 10 years of continuous combined HRT. Mean total cholesterol levels were significantly reduced after 10 years of therapy (p = 0.012), with no significant changes in serum triglyceride and low-density lipoprotein (LDL)-cholesterol levels from baseline values at this time. High-density lipoprotein (HDL)-cholesterol levels, however, were reduced by 15.4% (p < 0.001). In conclusion, 10 years of continuous combined HRT resulted in a significant and sustained increase in BMD. This treatment regimen therefore appears to be well suited for the long-term prevention of osteoporosis in postmenopausal women.

Adult↗
PubMed1998

Expression of the vascular endothelial growth factor C receptor VEGFR-3 in lymphatic endothelium of the skin and in vascular tumors.

It is difficult to identify lymph vessels in tissue sections by histochemical staining, and thus a specific marker for lymphatic endothelial cells would be more practical in histopathological diagnostics. Here we have applied a specific antigenic marker for lymphatic endothelial cells in the human skin, the vascular endothelial growth factor receptor-3 (VEGFR-3), and show that it identifies a distinct vessel population both in fetal and adult skin, which has properties of lymphatic vessels. The expression of VEGFR-3 was studied in normal human skin by in situ hybridization, iodinated ligand binding, and immunohistochemistry. A subset of developing vessels expressed the VEGFR-3 mRNA in fetal skin as shown by in situ hybridization and radioiodinated vascular endothelial growth factor (VEGF)-C bound selectively to a subset of vessels in adult skin that had morphological characteristics of lymphatic vessels. Monoclonal antibodies against the extracellular domain of VEGFR-3 stained specifically endothelial cells of dermal lymph vessels, in contrast to PAL-E antibodies, which stained only blood vessel endothelia. In addition, staining for VEGFR-3 was strongly positive in the endothelium of cutaneous lymphangiomatosis, but staining of endothelial cells in cutaneous hemangiomas was weaker. These results establish the utility of anti-VEGFR-3 antibodies in the identification of lymphovascular channels in the skin and in the differential diagnosis of skin lesions involving lymphatic or blood vascular endothelium.

Adult↗