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C D Fletcher

Publications and source records attributed to C D Fletcher.

At least 109 records · Page 6Linked to original sources
PubMed1997

Follicular dendritic cell sarcoma. Clinicopathologic analysis of 17 cases suggesting a malignant potential higher than currently recognized.

BACKGROUND: The goal of this study was to characterize the clinicopathologic features of follicular dendritic cell sarcoma, a very uncommon neoplasm. METHODS: The 17 cases were collected from the consultation and surgical pathology files of the authors, including 8 previously reported cases. The histologic and immunohistochemical features and outcome were analyzed. RESULTS: The patients had a median age of 40 years, with a slight female predominance. Seven patients presented with enlarged lymph nodes, and ten presented with tumor in extranodal sites. Two cases were associated with hyaline-vascular Castleman's disease. The tumors had an average greatest dimension of 6.7 cm. The most common histologic feature was a storiform or fascicular array of spindle, ovoid, or polygonal cells with oval nuclei, delicate nuclear membrane, vesicular or granular chromatin, distinct nucleoli, indistinct cell borders, and frequently fibrillary cytoplasm. There were often scattered multinucleated forms. The tumor cells sometimes formed sheets, circular whorls, follicle-like structures, trabeculae, or pseudovascular spaces. There was a sprinkling of small lymphocytes, with or without cuffing around blood vessels. The neoplastic cells were immunoreactive for CD21 (17 of 17 cases), CD35 (17 of 17 cases), desmoplakin (10 of 17 cases), epithelial membrane antigen (14 of 16 cases), S-100 protein (6 of 17 cases), and CD68 (2 of 17 cases), but not cytokeratin. Ultrastructural studies showed villous processes connected by desmosomes. Only one harbored the Epstein-Barr virus. Among 13 patients with a median follow-up of 3 years, local recurrence occurred in 6, metastasis in 6, and 3 died of disease. CONCLUSIONS: Follicular dendritic cell sarcoma exhibits distinctive histologic features that permit its presumptive recognition, but a firm diagnosis requires confirmation with special studies. Because it has a significant recurrent and metastatic potential (the latter risk having been previously underestimated), it should be viewed as an intermediate grade malignancy. An intraabdominal location is associated with a particularly aggressive clinical course.

Adolescent↗
PubMed1997

Terminal differentiation of human liposarcoma cells induced by ligands for peroxisome proliferator-activated receptor gamma and the retinoid X receptor.

Induction of terminal differentiation represents a promising therapeutic approach to certain human malignancies. The peroxisome proliferator-activated receptor gamma (PPAR gamma) and the retinoid X receptor alpha (RXR alpha) form a heterodimeric complex that functions as a central regulator of adipocyte differentiation. Natural and synthetic ligands for both receptors have been identified. We demonstrate here that PPAR gamma is expressed at high levels in each of the major histologic types of human liposarcoma. Moreover, primary human liposarcoma cells can be induced to undergo terminal differentiation by treatment with the PPAR gamma ligand pioglitazone, suggesting that the differentiation block in these cells can be overcome by maximal activation of the PPAR pathway. We further demonstrate that RXR-specific ligands are also potent adipogenic agents in cells expressing the PPAR gamma/RXR alpha heterodimer, and that simultaneous treatment of liposarcoma cells with both PPAR gamma- and RXR-specific ligands results in an additive stimulation of differentiation. Liposarcoma cell differentiation is characterized by accumulation of intracellular lipid, induction of adipocyte-specific genes, and withdrawal from the cell cycle. These results suggest that PPAR gamma ligands such as thiazolidinediones and RXR-specific retinoids may be useful therapeutic agents for the treatment of liposarcoma.

Adipocytes↗
PubMed1997

Molecular abnormalities of the p53 pathway in dedifferentiated liposarcoma.

Dedifferentiated liposarcoma represents a distinct subtype of liposarcoma and is characterized by the presence of abrupt transition from well-differentiated liposarcoma to high-grade pleomorphic sarcoma (mostly MFH-like). A key role for p53 in tumour progression of this subset of liposarcomas has been suggested on the basis of p53 immunopositivity. A series of 14 dedifferentiated liposarcomas has been investigated by analysing the p53 gene and protein together with the p53-related molecules p21Waf1 and mdm2, to verify whether the p53 pathway is involved in the development and progression of this tumour type. The results indicate that the p53 gene is rarely involved in dedifferentiated liposarcoma (7 per cent of cases analysed) and that low percentages of p53 immunopositivity are still compatible with integrity of the p53 gene. This concept is also supported by the observed preservation of p21Waf1 immunoreactivity in all but the p53-mutated cases. By contrast, mdm2 overexpression emerges as the most frequent abnormality in dedifferentiated liposarcoma (57 and 78 per cent of cases in well-differentiated and high-grade areas, respectively).

Cell Differentiation↗
PubMed1997

Additional evidence of a variant translocation t(12;22) with EWS/CHOP fusion in myxoid liposarcoma: clinicopathological features.

It is well established that the majority of myxoid/round cell liposarcomas (LPS) are characterized by a reciprocal translocation t(12;16)(q13;p11) which at the molecular level results infusion of the CHOP and FUS/TLS genes. It is assumed that functional characterization of these genes may provide insight into the molecular pathogenesis of this tumour type. This study describes two new cases of myxoid/round cell LPS having a t(12;22). By reverse transcription-polymerase chain reaction (RT-PCR) it has been shown that this leads to fusion between the CHOP and EWS genes, thus indicating involvement of the EWS gene, at least occasionally, in yet another sarcoma type. Combining these two cases with two others which were recently similarly characterized at the molecular level, their clinicopathological features have been compared with cases having the more usual t(12;16). It was not possible to identify any clinical or pathological differences between these molecular genetic subsets. The relevance or significance of these gene fusion products in myxoid/round cell LPS remains to be determined.

Adult↗
PubMed1997

Cellular fibrous histiocytoma of the skin: evidence of a clonal process with different karyotype from dermatofibrosarcoma.

Recently, a distinct variant of cutaneous fibrous histiocytoma (FH) has been histologically characterized as a "cellular" subtype. This variant is often mistaken for sarcoma, including dermatofibrosarcoma protuberans. We report a case of cellular FH of the skin in which the cytogenetic analysis demonstrated a novel chromosome pattern, possibly allowing distinction from its histologic simulants.

Adult↗
PubMed1997

The clinical role of molecular genetics in soft tissue tumor pathology.

Cytogenetic and molecular analysis of soft tissue tumors has yielded a wealth of information over the past decade. Some of the genetic aberrations that have been identified appear to be fairly specific for individual tumor types. It is because of this specificity that these findings harbor the promise to become useful as diagnostic and/or prognostic markers. Technical advances that allow the application of cytogenetic and molecular techniques to archival material have been crucial in this respect. Molecular genetics has already become an integral part of the work-up of some tumors, e.g., small cell sarcomas of childhood, which demonstrate fairly characteristic translocations, often involving the Ewing's sarcoma gene. Some genetic abnormalities have become established as prognostic markers, such as the deletion of the short arm of chromosome 1 for neuroblastomas. Soft tissue tumor pathology has also benefitted from major advances in identifying genes that are critical in mesenchymal differentiation or cell cycle control. MyoD is a good example of a such a gene, that has become useful as a diagnostic tool in rhabdomyosarcomas. Beyond potential practical applications of cytogenetic and molecular analyses in the diagnosis of these tumors, we also review their impact on several philosophical concepts concerning soft tissue neoplasia.

Child↗
PubMed1997

Dedifferentiated myxoid liposarcoma: a clinicopathological study suggesting a closer relationship between myxoid and well-differentiated liposarcoma.

Myxoid/round cell liposarcoma is arguably the commonest type of liposarcoma occurring in the extremities and may show gradual progression from low-grade, pure myxoid liposarcoma to high-grade round cell liposarcoma. Rarely myxoid/round cell liposarcoma is associated with areas of well-differentiated or pleomorphic liposarcoma (mixed liposarcoma). We describe the clinicopathological features of three unusual myxoid/round cell liposarcomas which showed morphological features of de novo dedifferentiation. All patients were male and were aged 66, 70 and 76 years, respectively. One lesion each arose in the retroperitoneum, inguinal region and peritoneal cavity. Histologically, in one case the myxoid/round cell component was juxtaposed to a high-grade non-lipogenic component resembling non-pleomorphic storiform 'malignant fibrous histiocytoma' ('MFH'), one case showed a combination of myxoid liposarcoma and a high-grade myxofibrosarcoma-like component (so-called myxoid 'MFH'), and in the third case, a well-differentiated myxoid liposarcoma with a discontinuous micronodular pattern of dedifferentiation was seen. Follow-up information of 30, 28 and 26 months revealed two recurrences each in two patients. These patients died of postoperative pulmonary embolism and abdominal haemorrhage, respectively; systemic metastases were not noted. These cases demonstrate that myxoid/round cell liposarcoma can show, albeit very rarely, histological features of dedifferentiation. Cases like these, combined with the occurrence of mixed-type liposarcoma (well-differentiated/myxoid liposarcoma) and the vicinity of chromosomal regions involved by specific karyotypic aberrations in these tumours, suggest that myxoid/round cell liposarcoma and well-differentiated liposarcoma (including its dedifferentiated variant) are more closely related in biological terms than is generally believed.

Abdominal Neoplasms↗
PubMed1997

The cytogenetics of lipomatous tumours.

Precise classification of lipomatous tumours sometimes presents a challenge to even the most experienced pathologist. Because the different types of lipomatous tumour exhibit significantly different biological behaviours, it is of utmost importance that the correct diagnosis be made. In morphologically difficult cases, identification of characteristic cytogenetic aberrations that correlate with histological subtype can facilitate the correct diagnosis.

Chromosome Aberrations↗
PubMed1997

Aggressive angiomyxoma: reappraisal of its relationship to angiomyofibroblastoma in a series of 16 cases.

Aggressive angiomyxoma is a distinctive soft tissue tumor associated with a high risk of local recurrence but lacks metastatic potential. This tumour occurs nearly exclusively in the soft tissues of the pelvis and perineum of adult women. The line of differentiation is not firmly established, but a fibroblastic/myofibroblastic origin has been proposed. We report 16 new cases of aggressive angiomyxoma of the pelvic soft tissue in women. In all cases bundles of cells, most often adjacent to vessels, with histological features of smooth muscle cells were identified. In 11 of 14 cases the myoid bundles were immunoreactive for desmin; they were also positive for smooth muscle actin in 10 of 11 cases. In 13 of 14 cases lesional stromal cells showed immunoreactivity for desmin. Three cases showed areas with histological features similar to those of angiomyofibroblastoma of the vulva, thus representing previously undescribed morphological overlap between these two entities. We conclude that aggressive angiomyxoma and angiomyofibroblastoma are related neoplasms in a spectrum of tumours showing myofibroblastic origin. Furthermore, the demonstration of immunoreactivity for desmin in aggressive angiomyxomas implies that this antibody is not helpful in discriminating between these two tumours, and the principal means of distinction remains histomorphological analysis.

Adult↗
PubMed1997

Kaposiform hemangioendothelioma in adults. Clinicopathologic and immunohistochemical analysis of three cases.

Kaposiform hemangioendothelioma (KHE) is a rare vascular neoplasm that previously has been described only in children. We report three cases occurring in adults. The patients, two men and one woman, were aged 64, 55, and 48 years, respectively. Lesions arose on the chest wall, the lateral aspect of the neck, and in the groin and buttock, and each was situated in superficial soft tissue. Tumor size ranged from 0.9 to 7 cm. Histologically, in all cases a lobular or nodular growth pattern of densely packed spindle-shaped tumor cells closely associated with small slitlike and sievelike blood vessels was seen. Within one lesion, small nodules of plumper, epithelioid tumor cells were identified. Well-formed capillaries frequently containing fibrin thrombi were observed mainly in the periphery of tumor nodules. Areas of hemorrhage and hemosiderin deposits were observed in two cases. Associated lymphangiomatosis composed of diffusely infiltrating lymphatic spaces of the dermis and subcutis was present in one case. Nuclear atypia was minimal in all cases, and mitotic figures were rare in two cases; in one case up to 6 mitoses in 10 high-power fields were noted focally. Immunohistochemically, well-formed capillaries stained positively for all the vascular markers used; however, endothelial cells lining the small slitlike and sievelike vascular spaces did not stain for von Willebrand factor. At least focally, actin-positive pericytes were seen. Neoplastic spindled cells stained only focally for CD34 and CD31. Two lesions were excised with clear margins; in one case only repeated biopsies were done. Follow-up information between 14 and 28 months revealed no sign of recurrence or metastasis. In adults, the differential diagnosis of KHE comprises especially Kaposi's sarcoma and spindle cell hemangioendothelioma; further differential diagnoses include tufted hemangioma and cellular capillary hemangioma, which occur rarely in adults.

Actins↗
PubMed1997

Cutaneous pilar leiomyoma: clinicopathologic analysis of 53 lesions in 45 patients.

As cutaneous pilar leiomyomas have received little attention in the recent literature, 53 lesions from 45 patients were studied to analyze their clinicopathologic features. There was an equal distribution between both sexes; most patients were adults with a wide age distribution. Both multiple (29 lesions from 21 patients) and solitary tumors (18 patients) were included. Lesions on the extremity (29 tumors) were common in both groups, whereas truncal tumors (11) were confined largely to patients with multiple lesions. In six patients the number of lesions was not specified. The tumors were painful in 17 patients. Three patients had a positive family history of similar lesions. Histologic study revealed ill-defined bundles of well-differentiated smooth muscle cells in the reticular dermis in all cases, although nine lesions had a more nodular pattern. Overlying epidermal hyperplasia was noted in 29 cases (54.7%). Immunohistochemically there appeared to be an increased number of nerve fibers within and surrounding the tumors. Mitotic activity was observed in 15 lesions (28.3%), 13 of which had <1 mitosis per 10 high power fields (HPF); the remaining two lesions had 1-2 mitoses per 10 HPF. Follow-up was available in 10 of these mitotically active tumors and ranged from 9 months to 7 years. There was no recurrence in any of them. We have concluded tentatively that leiomyomas of arrector pili origin may exhibit a low mitotic activity of <1 per 10 HPF and that this does not adversely affect the prognosis for these patients.

Adolescent↗
PubMed1997

Primary metaplastic carcinoma (carcinosarcoma) of the skin. A clinicopathologic study of four cases and review of the literature.

Metaplastic carcinoma (carcinosarcoma, sarcomatoid carcinoma, malignant mixed tumor) is a biphasic tumor comprising malignant epithelial and heterologous mesenchymal elements. Primary cutaneous cases are rare, with only seven cases documented in the English literature to date. We present four further cases, including three that developed in association with squamous cell carcinoma and one in an eccrine porocarcinoma. Heterologous malignant mesenchymal elements included malignant osteosarcoma, chondrosarcoma, leiomyosarcoma, and rhabdomyosarcomas. In contrast to metaplastic carcinomas arising in visceral sites, those primarily arising in the skin do not appear to behave in a very aggressive manner (Recurrence rate 22%, metastasis rate 22%, overall mortality 11%). However, the numbers involved are small and the follow-up period is short. In view of recent developments and progress in our understanding of the possible histogenesis of such tumors, we suggest that metaplastic carcinoma rather than carcinosarcoma is the most appropriate term with which to describe these very rare cutaneous neoplasms.

Acrospiroma↗
PubMed1997

Mixed tumors and myoepitheliomas of soft tissue: a clinicopathologic study of 19 cases with a unifying concept.

We report 19 unusual cases of mixed tumors and myoepitheliomas arising in soft tissues. The neoplasms occurred in 12 males and seven females. The age at diagnosis ranged from 2 to 83 years (mean 35, median 30). Eight tumors arose in the upper limb, six in the lower limb, three in the trunk, and two in the head and neck region. Three cases involved both dermis and subcutis; the remainder arose in subcutaneous (13 cases) or deep subfascial soft tissue (three cases). The most common presenting complaint was a painless swelling, with duration ranging from 2 weeks to 1 year (median 2.5 months). Microscopically, the tumors were predominantly well circumscribed and lobulated. Six cases showed a focally infiltrative margin. Cardinal morphologic features included nests, cords, and ductules of epithelioid cells and/or nests of spindled cells within a hyalinized to chondromyxoid stroma. One tumor was predominantly composed of myoepithelial cells and devoid of epithelial differentiation (i.e., ductules). Cytoplasmic hyaline inclusions were noted in two cases; squamous differentiation was seen in one case. Osteoid production and/or metaplastic bone was observed in three tumors. Chondroid differentiation (usually mature) was seen in four cases. Adipocytic differentiation was seen in two tumors. Mitotic activity was variable but generally scant; atypical mitotic figures were not identified. By immunohistochemistry, 16 of 16 cases expressed pan-keratin; 16 of 17 S-100 protein; six of 14 alpha smooth muscle actin (IA4); two of 10 muscle specific actin (HHF-35); two of 10 desmin; three of 11 glial fibrillary acidic protein; and three of 16 epithelial membrane antigen. Clinical follow-up was available in 10 patients and ranged from 6 months to 20 years (mean 4.25 years, median 2 years). Two patients developed local recurrence; metastasis to lung and lymph nodes were observed in two additional patients. Both of the latter patients died. We believe that these findings expand the concept of cutaneous mixed tumors to include neoplasms composed predominantly of myoepithelial cells and to include tumors arising in deeper subcutaneous and/or subfascial tissues. The clinical behavior of such neoplasms, when arising in soft tissues, may be difficult to predict but is most often benign; however, a minority of lesions metastasize. Until larger studies with longer follow-up are available, treatment and prognostication are probably best based on criteria used in comparable salivary gland tumors.

Adult↗
PubMed1997

"Proximal-type" epithelioid sarcoma, a distinctive aggressive neoplasm showing rhabdoid features. Clinicopathologic, immunohistochemical, and ultrastructural study of a series.

Eighteen examples of an unusual malignant soft-tissue neoplasm, the morphology of which ranged from that of "atypical" epithelioid sarcoma to that of a rhabdoid tumor or undifferentiated carcinoma (with transitional forms) are described. Patients included 11 males and seven females; their median age was 35.5 years with most patients aged 20 to 40 years. Development of a mass was the main presenting symptom. Six tumors developed in the pelvis and perineal region, four in the pubic region and vulva, three in the buttocks, one in the deep soft tissues of the left hip, one on the penis, one in left forearm, one in left axilla, and one on the occiput. Tumor size ranged from 1 to 20 cm (median, 4 cm). On microscopic examination, the tumor cells invaded the subcutaneous or deep soft tissues, had prominent epithelioid or rhabdoid features, had marked cytologic atypia, and grew in a multinodular pattern in half of the cases. Areas of necrosis were often seen. A granuloma-like pattern reminiscent of that observed in classic epithelioid sarcoma was observed in only two cases. Immunohistochemically, positivity for cytokeratin, epithelial membrane antigen, and vimentin was seen in all but one of the cases. Of 16 cases, 10 and eight tumors reacted with desmin and CD34, respectively; five of 15 reacted at least focally with smooth-muscle actin, whereas three of 13 and one of 10 reacted for HMB-45 and carcinoembryonic antigen, respectively. S-100 protein and CD31 yielded negative results. Seven tumors were investigated at the ultrastructural level, four of which showed prominent intracytoplasmic intermediate filament aggregates, often accumulating into paranuclear whorls, which is in keeping with the rhabdoid phenotype. Five tumors showed features of epithelial differentiation (i.e., tonofilament-like structures or desmosomes or both), whereas one tumor displayed features of myofibroblastic differentiation. Differential diagnoses include mainly conventional epithelioid sarcoma, extrarenal malignant rhabdoid tumor, epithelioid malignant peripheral nerve sheath tumor, melanoma, rhabdomyosarcoma, and undifferentiated carcinoma. Follow-up information on 14 patients (range, 4 months to 8 years; median, 19 months) revealed local recurrence in one case and metastatic dissemination in six patients, leading to death in five. In our opinion, the above-described neoplasms represent a usually "proximal-type" of epithelioid sarcoma. In contrast to the conventional, "distal-type" epithelioid sarcoma, the proximal variant is characterized by a predominantly large-cell, epithelioid cytomorphology, marked cytologic atypia, frequent occurrence of rhabdoid features, and lack of a granuloma-like pattern in most cases. It appears to be somewhat more aggressive (or at least metastasizes earlier) than usual epithelioid sarcoma.

Adolescent↗
PubMed1997

Desmoplastic small round cell tumors of the paratesticular region. A report of six cases.

Desmoplastic small round cell tumor (DSRCT) typically occurs in the abdomen but may also present at other sites. We report six cases of paratesticular DSRCT. The patients, who ranged in age from 17 to 37 (mean, 28) years, presented with a scrotal mass (five cases) or testicular pain (one case). Grossly, the tumors were white to tan and firm. Typically, they involved the paratesticular soft tissue, serosal surfaces and the epididymis near the junction with the rete testis. Microscopically, the tumors consisted of nests of mitotically active "small blue cells" with scant cytoplasm embedded in a densely fibrotic stroma. Two tumors showed focal tubule formation; one of these also formed rosettes. The tumors exhibited the typical immunophenotype of DSRCT (positivity for keratin, vimentin, desmin, and neuron-specific enolase but nonreactivity with HBA-71 and anti-S-100). Four tumors metastasized to lymph nodes (retroperitoneal, cervical, and two unspecified); pulmonary metastases occurred in one of these cases and in one patient without lymph node metastases. One of the above patients treated with chemotherapy, died of disease at 16 months. The patients with pulmonary metastases (one of whom also had lymph node metastases) were treated with aggressive chemotherapy and are alive and apparently disease-free at 2.5 and 3 years, respectively. Three of the six patients, two of whom had known metastases, were lost to follow-up. The DSRCT of the paratestis has histologic and immunohistochemical features identical to its abdominal counterpart and must be differentiated from other "small blue cell" tumors of the paratesticular region.

Adolescent↗
PubMed1997

Epithelioid hemangioendothelioma of skin and soft tissues: clinicopathologic and immunohistochemical study of 30 cases.

Epithelioid hemangioendothelioma of soft tissues (EHE) represents a distinct entity with an unpredictable clinical course. We analyzed the clinicopathologic and immunohistochemical features in a series of 30 patients. Patient age range was 16-74 years (median 50); 18 of 30 patients were female. Eight tumors arose in the lower and two in the upper extremities, seven on the trunk, five each in the head/ neck and anogenital regions, two in the mediastinum, and one in the abdomen. Seventeen neoplasms were located in deep soft tissues, nine were subcutaneous or perifascial, and four were dermal; size ranged from 0.4 to 10 cm; in 11 cases the tumor was > 5 cm. Tumors with an infiltrative growth pattern were more common than entirely circumscribed lesions. The tumors were composed histologically of short strands, cords, or small clusters of epithelioid, round, to slightly spindled endothelial cells that formed at least focally, intracellular lumina and were set in a frequently myxohyaline stroma. Thirteen of 30 lesions showed angiocentric growth, which was occlusive in many cases. Immunohistochemically, all cases tested were positive for at least one endothelial marker (CD31, CD34, factor VIII, Ulex europaeus), six of 23 (26%) were positive for cytokeratin, and five of 11 (45%) were positive for alpha-smooth muscle actin. Median follow-up of 36 months (range 2-96) in 24 cases showed local recurrence in three cases and systemic metastases in five cases (21%); four patients (17%) died of tumor. Although more aggressive histologic features (striking nuclear atypia in eight cases, numerous spindled cells in 10, more than two mitoses per 10 high-power fields in nine, and small, more solid angiosarcomalike foci in four cases) tended to be related to poor clinical outcome, there was no clear correlation. Two metastasizing cases showed no histologically atypical features whatever. We suggest that EHE of soft tissue is better regarded as a fully malignant, rather than borderline, vascular neoplasm, albeit the prognosis is better than in conventional angiosarcoma.

Adolescent↗
PubMed1997

Cytogenetic analysis of subcutaneous angiolipoma: further evidence supporting its difference from ordinary pure lipomas: a report of the CHAMP Study Group.

Subcutaneous angiolipomas are benign soft-tissue lesions consisting of two mesenchymal elements (i.e., adipose tissue and blood vessels) and having distinct clinical features. They usually are multiple, with an obvious male predominance, and hereditary occurrence has been described. Twenty subcutaneous angiolipomas from 10 patients with typical clinical and morphologic features were reviewed. All lesions had a normal karyotype. This finding is in striking contrast with ordinary lipomas, spindle-cell and pleomorphic lipomas, lipoblastomas, and hibernomas, most of which have characteristic clonal chromosomal aberrations. The normal karyotype of subcutaneous angiolipoma as well as its distinct clinical and morphologic features suggest a different pathogenesis from pure lipomas.

Adult↗