Limb Girdles Research Articles

First plesiosaur remains from the lower Cretaceous of the Neuquén Basin, Argentina

Plesiosaurs constitute a monophyletic group whose stratigraphical range is uppermost Triassic to uppermost Cretaceous (Brown, 1981). They were large predatory marine reptiles, highly adapted for submarine locomotion, with powerful paddle-like limbs and heavily reinforced limb girdles (Saint-Seine, 1955; Romer, 1966; Carroll, 1988; Benton, 1990). The Plesiosauria clade belongs to the Sauropterygia, which has recently been hypothesized as the sister-group of the Ichthyosauria. Together with that clade they form the Euryapsida (Caldwell, 1997). The Sauropterygia can be subdivided into relatively plesiomorphic stem-group taxa from the Triassic (Placodonts, Nothosauroids, and Pistosauroids), and the obligatorily marine crown-group Plesiosauria (Rieppel, 1999). Plesiosaurs are traditionally divided into two superfamilies: Plesiosauroidea, with usually small heads and long necks; and Pliosauroidea, with larger heads and shorter necks (Welles, 1943; Persson, 1963; Brown, 1981). Plesiosauroidea contains three families: Plesiosauridae, Cryptoclididae, and Elasmosauridae (Brown, 1981; Brown and Cruickshank, 1994). The validity of the Polycotylidae Cope, 1869, has long been questioned and its phylogenetic position among Plesiosauria debated, as many consider it to be related to the Pliosauridae or to be a sister-group of the Elasmosauridae (Sato and Storrs, 2000; O'Keefe, 2001).

FIRST PLESIOSAUR REMAINS FROM THE LOWER CRETACEOUS OF THE NEUQUÉN BASIN, ARGENTINA

Plesiosaurs constitute a monophyletic group whose stratigraphical range is uppermost Triassic to uppermost Cretaceous (Brown, 1981). They were large predatory marine reptiles, highly adapted for submarine locomotion, with powerful paddle-like limbs and heavily reinforced limb girdles (Saint-Seine, 1955; Romer, 1966; Carroll, 1988; Benton, 1990). The Plesiosauria clade belongs to the Sauropterygia, which has recently been hypothesized as the sister-group of the Ichthyosauria. Together with that clade they form the Euryapsida (Caldwell, 1997). The Sauropterygia can be subdivided into relatively plesiomorphic stem-group taxa from the Triassic (Placodonts, Nothosauroids, and Pistosauroids), and the obligatorily marine crown-group Plesiosauria (Rieppel, 1999). Plesiosaurs are traditionally divided into two superfamilies: Plesiosauroidea, with usually small heads and long necks; and Pliosauroidea, with larger heads and shorter necks (Welles, 1943; Persson, 1963; Brown, 1981). Plesiosauroidea contains three families: Plesiosauridae, Cryptoclididae, and Elasmosauridae (Brown, 1981; Brown and Cruickshank, 1994). The validity of the Polycotylidae Cope, 1869, has long been questioned and its phylogenetic position among Plesiosauria debated, as many consider it to be related to the Pliosauridae or to be a sister-group of the Elasmosauridae (Sato and Storrs, 2000; O'Keefe, 2001). Plesiosaurs have an almost worldwide distribution in the Jurassic and Late Cretaceous, being especially abundant in Europe (Andrews, 1910; Brown, 1981; Bardet, 1995) and North America, respectively (Welles, 1943, 1952). It is worth mentioning the scarcity of these reptiles in the cosmopolitan Lower Cretaceous (Welles, 1962; Gasparini and Goni, 1985; Cruickshank, 1997). The only known elasmosaurid genera from this time are Brancasaurus Wegner, 1914, from the Berriasian of Germany (Wegner, 1914) and Alzadasaurus Welles, 1943, from the Aptian of Colombia (Welles, 1962; Goni and Gasparini, 1983). No remains of this family have been described from Valanginian or Hauterivian ages. The oldest …

SYSTEMATICS OF THE AMPHISBAENIA (LEPIDOSAURIA:SQUAMATA) BASED ON MORPHOLOGICAL EVIDENCE FROM RECENT AND FOSSIL FORMS

Amphisbaenians are a poorly known group of squamate reptiles with over 150 extant species in 23 genera. They live almost exclusively under loose or sandy soil in tropical to temperate areas around the world, and their anatomy is modified in many ways related to this lifestyle. Most recent studies recognize four families within Amphisbaenia—Bipedidae, Amphisbaenidae, Trogonophidae, and Rhineuridae. Only the Rhineuridae are well represented in the fossil record. Two exclusively fossil families, Hyporhinidae and Crythiosauridae, have also been recognized in some studies. In this paper, a phylogenetic study of the Amphisbaenia is presented based on morphological characters investigated in living and fossil forms. Amphisbaenian monophyly is supported, but the recent identification of the late Cretaceous Sineoamphisbaena hextabularis† as a primitive amphisbaenian is not supported. The monophyly of two of the four families of extant amphisbaenians is upheld, with one family being more inclusive than previously thought. Amphisbaenidae is substantially revised, with several taxa previously included in the family being more closely related to rhineurids, and with Blanus representing a basal amphisbaenian. Rhineuridae is also revised to include the previously recognized fossil family Hyporhinidae. Trogonophidae is the sister-group to the remaining amphisbaenids, and together they form the sister-group to the expanded rhineurid clade. Bipes is the most basal amphisbaenian and Blanus is the sister-group to all remaining amphisbaenians. Crythiosauridae is removed from the Amphisbaenia because no support was found for its inclusion.The deep nesting of rhineurids within Amphisbaenia found here contrasts with their extensive fossil record beginning in the late Paleocene. This hypothesis implies significant gaps in the fossil record of all other amphisbaenian taxa, and the reacquisition of some seemingly primitive features in some fossil rhineurids. However, the condition of the limbs in extinct rhineurids is uncertain and, if they are found to be present, the related characters could place them in a more basal position, which would then alter interpretations of character evolution. The basal positions of Bipes and Blanus imply that a round-headed cranial shape is the primitive condition for Amphisbaenia in contrast to some previous hypotheses.In this analysis, amphisbaenians are nested within Squamata, in contrast to a hypothesized relationship as the sister-group to the remainder of squamates (alone, with snakes, or with another group of limbless burrowing lizards, Dibamidae). Weak support was found for a relationship between amphisbaenians and Dibamidae as previously suggested by some other analyses, but this is based mainly on reduction and absence features and the sister-group to Amphisbaenia is considered here to be inconclusive. Sineoamphisbaena† is found to be related to macrocephalosaurs, an extinct group previously placed with Teiidae, but placed basally among squamates by this analysis.Morphological analyses of squamates in this study include numerous features associated with reduced or absent limbs and limb girdles, as well as other specializations presumed to be related to a burrowing lifestyle. These characters are often hypothesized to have been convergently acquired among limbless squamate clades and have been excluded or downweighted in some previous analyses. This approach is difficult to implement here because further anatomical investigations of these structures revealed useful variation for resolving relationships within amphisbaenians. Future studies will require new approaches that can address the convergence problem in a manner that does not involve the added problem of removing characters informative at other levels. They should also include the addition of novel data sets.

The Evolution of Paired Fins

The Archipterygium is Gegenbaur’s most lasting contribution to the study of vertebrate limb evolution. This transformational hypothesis of gill arches to limb girdles, rays to fins, and proposal of a vertebrate fin-limb groundplan, is generally treated as a flawed alternative to the more widely accepted lateral fin-fold hypothesis of vertebrate limb evolution. When compared to the phylogenetic distribution and diversity of fins and limbs, both hypotheses fail. Dermal skeletal lateral folds, spines and keels originate repeatedly in vertebrate evolution, but paired fins with girdles originate at pectoral level and are anteroposteriorly restricted. Pelvic fins emerge later in phylogeny; pectoral and pelvic appendages primitively differ. Endoskeletal girdles never exhibit characteristics of gill arches. The emergent sequence of paired fin evolution depends upon phylogenetic hypotheses within which extant agnathan interrelationships are uncertain; positions of jawless fossil fish along the gnathostome stem are insecure; the fossil data set is patchy. However, certain features of the data set are robust. This has prompted a reconsideration of Gegenbaur’s hypothesized arch-girdle relationship, and an iterative homology between scapulocoracoid and extrabranchial cartilages is suggested. No transformation of arch to girdle is necessarily implied, but some signal of developmental relatedness is predicted.

Pleomorphic liposarcoma: clinicopathologic, immunohistochemical, and follow-up analysis of 63 cases: a study from the French Federation of Cancer Centers Sarcoma Group.

The clinicopathologic and immunohistochemical features of 63 pleomorphic liposarcomas are presented. There were 35 men and 28 women (median age 63 years; range 18-93 years). Tumor size ranged from 2 to 23 cm (median 10 cm). Tumor locations included lower extremity (36.5%), especially the thigh (28.5%), limb girdles (17.5%), upper extremity (16%), thoracoabdominal wall (9.5%), and internal trunk (20.5%). A total of 75% were deep seated and/or extracompartmental. Histologically, lesions show a varying combination of lipogenic and nonlipogenic areas characterized by malignant fibrous histiocytoma-like, round cell liposarcoma-like, and/or epithelioid/carcinoma-like features. A pericytic pattern was focally present in 15 (24%) tumors. Eighteen (29%) lesions were grade 2, and 45 (71%) were grade 3 sarcomas. Tumor necrosis was observed in 51 (81%) cases, vascular invasion in three, and mitotic counts ranged from 3 to 124 per 10 high power fields (median 25). Lipogenic areas were S-100 protein immunoreactive, at least focally, in 20 of 42 (48%) cases. Nonlipogenic areas showed focal reactivity for smooth muscle actin (24 of 49; 49%), desmin (9 of 48; 19%), CD34 (18 of 45; 40%), S-100 protein (5 of 49, 10%), CD68 (6 of 46, 13%), and epithelial membrane antigen (13 of 49, 26.5%). Epithelioid areas showed epithelial membrane antigen (4 of 11; 36%) but not cytokeratin (0 of 11) reactivity. Treatment procedures in 51 patients consisted of simple tumorectomy (16) and wide excision (33). Five and 31 patients received neoadjuvant and adjuvant chemotherapy and/or radiation therapy, respectively. Follow-up (48 patients, range 7-276 months; median 38 months) showed a 45% local recurrence rate and a 42.5% metastasis rate, metastases occurring mostly in lungs and pleura. Seventeen patients (35%) died of disease, of whom none was metastatic at diagnosis. Five-year overall, metastasis-free, and local recurrence-free survivals were 57%, 50%, and 48%, respectively. Patient age > or =60 years, truncal tumor location, deep situation, tumor size >5 cm, vascular invasion, and incomplete tumor excision were significant adverse prognostic factors. Tumor grade and histology did not affect patient outcome. In conclusion, pleomorphic liposarcoma is a rare, often deep-seated and limb-based aggressive and metastasizing neoplasm of late adulthood. It shows a wide range of morphologic appearances, but tumor grade and histology have no effect on patient outcome.

Extraskeletal myxoid chondrosarcoma: A clinicopathologic, immunohistochemical, and molecular analysis of 18 cases

Extraskeletal myxoid chondrosarcoma (EMCS) is an uncommon clinicopathologically well-defined tumor, but its pathogenesis and biologic behavior are poorly understood. We reviewed 18 cases of EMCS to verify clinicopathologic features and immunohistochemical profiles together with molecular detection of the tumor-specific fusion genes. The tumors were located mainly in the proximal extremities and limb girdles (72%). Two tumors arose at unusual anatomic sites: the finger and the hip joint. Nine of the 17 followed-up patients were alive and disease free, 4 were alive with recurrences and/or metastases, and 4 died of the tumor. Fifteen tumors showed typical features of EMCS, and 3 had hypercellular areas in addition to conventional EMCS areas. The tumors were variably immunoreactive for S-100 protein (50%), NSE (89%), peripherin (60%), and synaptophysin (22%). Chromogranin A and some epithelial markers (AE1/AE3, CAM5.2, and epithelial membrane antigen) were entirely negative. Frequent expressions of the neural/neuroendocrine markers suggest possible neural/neuroendocrine differentiation in at least some EMCSs, in addition to chondroid differentiation. In a reverse-transcription polymerase chain reaction (RT-PCR) assay using paraffin-embedded specimens, EWS-CHN or TAF2N-CHN fusion gene transcripts characteristic of EMCS could be detected in 15 (83%) of the 18 cases: EWS-CHN type 1 in 11 cases, EWS-CHN type 2 in 1, and TAF2N-CHN in 3. Three fusion-negative cases included 2 conventional EMCSs and 1 considered a “cellular” variant of the tumor. None of 30 other soft tissue and bone tumors with myxoid or chondroid morphology that we examined contained these fusion genes. Thus, RT-PCR detection of EWS-CHN or TAF2N-CHN fusion gene using archival paraffin-embedded tissue is a feasible and useful ancillary technique for the diagnosis of EMCS. HUM PATHOL 32:1116-1124. Copyright © 2001 by W.B. Saunders Company

Cellular myxoma of soft tissue: a clinicopathological study of 38 cases confirming indolent clinical behaviour.

To characterize the clinicopathological features and biological potential of a group of soft tissue lesions with morphology intermediate between intramuscular myxoma and low-grade myxofibrosarcoma. Thirty-eight lesions in 37 patients were retrieved from the authors' consultation files. Clinical and follow-up data were obtained and the lesions were also studied immunohistochemically. Tumours occurred in adults aged 25-83 years (mean 51.9 years) with a slight predominance in females. All cases, except two, were solitary. The extremities were preferentially involved (18 lower limb; nine upper limb), with seven lesions arising around the upper (2/7) and lower limb (5/7) girdles and four lesions occurring at other locations. Twenty-nine of 31 of the tumours, for which the depth was known, were situated deep to the superficial fascia, although only 19 were strictly intramuscular. Histologically these lesions were both more cellular and more vascular than intramuscular myxoma, while lacking the cytological pleomorphism, nuclear atypia and curvilinear vascular pattern characteristic of low-grade myxofibrosarcoma. CD34 positivity in lesional cells was identified in 17/30 (57%) cases, probably reflecting their fibroblastic nature. Staining for alpha-smooth muscle actin was focally positive in 3/30 (10%) cases, while desmin and S100 protein staining were consistently negative. Clinical follow-up data (available in 22 cases; median duration 30 months) demonstrate that these lesions behave in a benign fashion with only a small risk of local recurrence if not excised completely; in this study only two tumours recurred, both of which originally had been incompletely excised. None metastasized. The risk of recurrence in this group of lesions which we have designated 'cellular myxoma' appears to be low. Consequently simple complete local excision is most often adequate treatment. Longer follow-up (5-10 years or more) in a larger number of cases will be important in more definitively confirming the natural history of these lesions.

Function of the oblique hypaxial muscles in trotting dogs.

In trotting dogs, the pattern of activity of the obliquely oriented hypaxial muscles is consistent with the possible functions of (i) stabilization against vertical accelerations that cause the trunk to sag in the sagittal plane and (ii) stabilization against forces that tend to shear the trunk in the sagittal plane. To test these hypotheses, we compared the amount of activity of the intercostal and abdominal oblique muscles (i) when dogs carried additional mass (8-15% of body mass) supported over the limb girdles versus supported mid-trunk (test of sagittal bounce), and (ii) when dogs trotted up versus down a 10 degrees slope (test of sagittal shear). In response to the loading manipulations, only the internal oblique muscle responded in a manner that was consistent with stabilization of the trunk against forces that cause the trunk to sag sagittally. In contrast, when the fore-aft forces were manipulated by running up- and downhill, all four of the monitored muscles changed their activity in a manner consistent with stabilization of the trunk against sagittal shearing. Specifically, muscles with a craniodorsal orientation (external oblique and external intercostal muscles) showed an increase in activity when the dogs ran downhill and a decrease when they ran uphill. Muscles with a cranioventral orientation (internal oblique and internal intercostal muscles) exhibited the opposite pattern: increased activity when the dogs ran uphill and decreased activity when they ran downhill. Changes in activity of two extrinsic appendicular muscles, the serratus ventralis and deep pectoralis, during uphill and downhill running were also consistent with the sagittal shearing hypothesis. In contrast, changes in the level of recruitment of the oblique hypaxial muscles were not consistent with stabilization of the trunk against torques that induce yaw at the girdles. Hence, we suggest that the oblique hypaxial muscles of trotting dogs act to stabilize the trunk against sagittal shearing torques induced by limb retraction (fore-aft acceleration) and protraction (fore-aft deceleration).

Modular long-range regulation of Myf5 reveals unexpected heterogeneity between skeletal muscles in the mouse embryo.

The myogenic factor Myf5 plays a key role in muscle cell determination, in response to signalling cascades that lead to the specification of muscle progenitor cells. We have adopted a YAC transgenic approach to identify regulatory sequences that direct the complex spatiotemporal expression of this gene during myogenesis in the mouse embryo. Important regulatory regions with distinct properties are distributed over 96 kb upstream of the Myf5 gene. The proximal 23 kb region directs early expression in the branchial arches, epaxial dermomyotome and in a central part of the myotome, the epaxial intercalated domain. Robust expression at most sites in the embryo where skeletal muscle forms depends on an enhancer-like sequence located between -58 and -48 kb from the Myf5 gene. This element is active in the epaxial and hypaxial myotome, in limb muscles, in the hypoglossal chord and also at the sites of Myf5 transcription in prosomeres p1 and p4 of the brain. However later expression of Myf5 depends on a more distal region between -96 and -63 kb, which does not behave as an enhancer. This element is necessary for expression in head muscles but strikingly only plays a role in a subset of trunk muscles, notably the hypaxially derived ventral body muscles and also those of the diaphragm and tongue. Transgene expression in limb muscle masses is not affected by removal of the -96/-63 region. Epaxially derived muscles and some hypaxial muscles, such as the intercostals and those of the limb girdles, are also unaffected. This region therefore reveals unexpected heterogeneity between muscle masses, which may be related to different facets of myogenesis at these sites. Such regulatory heterogeneity may underlie the observed restriction of myopathies to particular muscle subgroups.

Extraosseous Osteosarcoma of the Penis

Osteosarcomas have been reported as arising in a number of extraosseous primary sites, most commonly in the retroperitoneum and the muscles of the thighs and limb girdles, but also in a variety of other organs. We present a case arising in the penis, which we believe to be only the fifth reported in the literature and the only documented long-term survivor. Careful histopathological analysis and surgical management remain of key importance in the management of all sarcomas arising in soft tissue.

Extraskeletal myxoid chondrosarcoma: a reappraisal of its morphologic spectrum and prognostic factors based on 117 cases.

Extraskeletal myxoid chondrosarcoma (EMC), a phenotypically and genotypically distinctive entity, has generally been viewed as a low-grade sarcoma. No studies regarding clinical and morphologic prognostic factors have been performed on a large series of cases with long-term follow-up because of the rarity and protracted clinical course of EMC. The clinical, morphologic, and immunohistochemical features of 117 previously unreported cases were studied and statistically analyzed. The male-to-female ratio was 2:1. The median patient age was 52 years (range, 6-89 years), and the median tumor size was 7 cm (range, 1.1-25 cm). All tumors occurred within the deep subcutis or deeper soft tissues, with 80% occurring in the proximal extremities or limb girdles and 20% in the trunk. Most initial tumor excisions were intralesional or marginal. Follow-up information was available in 99 cases (median, 9 years: range, 2 months-22 years). Forty-eight patients were disease-free, and 41 patients had evidence of disease (18 of these had died of disease). Ten additional patients survived, but their disease status was unknown. There were local recurrences in 40 (48%) of 83 patients, 23 (58%) of whom had multiple local recurrences. Metastases occurred in 35 (46%) of 76 patients. The estimated 5-, 10-, and 15-year survival rates were 90%, 70%, and 60%, respectively. All cases had histologic features characteristic of classical EMC, at least focally. Cellular foci devoid of myxoid matrix and reminiscent of chondroblastoma, Ewing's sarcoma, monophasic and poorly differentiated synovial sarcoma, fibrosarcoma, and rhabdoid tumor were identified in 29% cases. Older patient age, larger tumor size, and tumor location in the proximal extremity or limb girdle were adverse prognostic factors identified by multivariate analysis. Metastasis also adversely affected survival, although local recurrence did not. This study shows that EMC has a unique clinical course, including a high rate of local recurrence, prolonged survival after metastasis in some cases, and eventually a high rate of death due to tumor. These features distinguish EMC from low-grade sarcomas. This study shows that histologic grading is of no prognostic value in EMC because prognosis is dictated primarily by certain clinical features. Histologic recognition of classical EMC and cellular and solid, nonmyxoid variants is important, however, in view of EMC's distinctive biologic behavior.

Primary chondrosarcoma of long bones and limb girdles

Chondrosarcomas are common solid malignant tumors of bone, second in incidence only to osteosarcomas. The biologic evolution of chondrosarcomas is slow, requiring long follow-up intervals for meaningful survival analysis. This study describes the clinicopathologic profiles of 344 patients, 194 male and 150 female (M:F, 1.3:1.0), with primary chondrosarcoma of long bones and limb girdles seen at 1 institution over a period of 80 years. The average age at presentation was 46 years (range, 5-82 years). The pelvis was the most common location (1.7% of all patients). Local pain was the most frequently reported initial symptom (81.4%). Survival analysis was limited to 233 patients whose primary treatment was given at the Mayo Clinic. All 233 patients had potential follow-up of at least 5 years. The overall 5-year survival rate was 77% (the expected rate was 96%). Local recurrence developed in 19.7% of patients and metastatic lesions in 13.7%. The recurrence rate was higher for tumors of the shoulder and pelvis than for tumors of long bones. Radiographically, chondrosarcomas had a characteristic appearance, including a combination of bone expansion and cortical thickening. Entering the tumor at surgery increased the risk of local recurrence. Histologic tumor grade was an important predictor of local recurrence and metastasis. With adequate initial surgical intervention, chondrosarcoma is primarily a local disease with a low metastatic rate.

Primary chondrosarcoma of long bones and limb girdles

Primary chondrosarcoma of long bones and limb girdles

Sclerosing Epithelioid Fibrosarcoma

We report 25 cases of a peculiar sclerosing epithelioid variant of fibrosarcoma (SEF) simulating an infiltrating carcinoma. The tumors occurred primarily in the deep musculature and were frequently associated with the adjacent fascia or periosteum. The patients' ages were 14 to 87 years (median, 45). Fourteen were male and 11 female. The tumors were located in the lower extremities and limb girdles (12 cases), trunk (9), upper limb girdles (2), and neck (2). They measured 2 to 14.5 cm in greatest dimension (median size, 7 cm) and were gray to white and firm. Histologically, the lesions were characterized by a proliferation of rather uniform, small, slightly angulated, round to ovoid epithelioid cells with sparse, often clear cytoplasm arranged in distinct nests and cords. In all cases there was prominent hyaline sclerosis, sometimes reminiscent of osteoid or cartilage and foci of conventional fibrosarcoma. Occasional myxoid zones with cyst formation and foci of hyaline cartilage, calcification, and metaplastic bone were also seen. Mitotic figures were generally scarce. Vimentin was detected in 13 of 14 cases, epithelial membrane antigen in seven, S100 protein in four, and neuron-specific enolase in two. Cytokeratins were detected with AE1/AE3 and CAM 5.2 in two cases. Leukocyte common antigen, CD68 antigen, HMB45, desmin, and alpha-smooth muscle actin were negative in all cases. In 13 of 14 cases, 75% or more of the cells stained for proliferating cell nuclear antigen (PCNA). Ki67 immunostaining with MIB 1 showed low proliferative activity in all cases, averaging 5% of tumor cells or less. In all cases, p53 was detected by immunohistochemical methods; bcl-2, an antiapoptosis marker, was detected in more than 90% of the cells in 11 of 12 cases. Ultrastructurally, both the epithelioid and spindled tumor cells had features of fibroblasts. Follow-up in 16 cases ranging from 13 months to 17 years 3 months (median, 11 years 4 months) revealed persistent disease or local recurrences in 53% of patients and metastases in 43%. The metastases were to the lungs (4 cases), skeleton (3), chest wall/pleura (3), pericardium (1), and brain (1). Four patients died of disease, four were alive with disease, two were known to be alive but disease status unknown, and six had no evidence of further disease at last follow-up. The data suggest that SEF is a relatively low-grade fibrosarcoma; yet it is fully malignant despite the presence of histologically benign-appearing foci. The proliferation markers PCNA and Ki67 did not correlate with prognosis.(ABSTRACT TRUNCATED AT 400 WORDS)

The distribution and retention of plutonium, americium and uranium in CBA/H mice

Groups of male and female CBA/H mice were given intraperitoneal injections of 40 kBq kg-1 of 239Pu, 241Am and 233U citrate solutions and the retention and distribution of the three radionuclides compared at times up to 448 days. Similar results were obtained for males and females and showed that: 1. Whole body retention at 448 days was very similar for 239Pu and 241Am, accounting for about 20% of injected activity for each nuclide; retention of 233U was much lower at about 3%. 2. The skeleton accounted for 85% or more of retained 239Pu, 241Am and 233U activity from 6 weeks after injection. 3. The greatest concentrations of each radionuclide were measured in the main body of the spine, limb girdles and ribs, with lowest concentrations in the paw bones, head bones and caudal vertebrae. The inhomogeneity of distribution was in the order Pu > U > Am; with a trend to more uniform activity with time. 4. Average bone doses to 448 days were calculated as about 1.6 and 1.7 Gy for 239Pu and 241Am, respectively, and 0.3 Gy for 233U, with ranges for individual bones of 0.7-3.0 Gy, 1.1-2.5 Gy and 0.1-0.6 Gy, respectively. Average liver doses to 448 days were calculated as about 0.9 Gy, 0.6 Gy and 0.007 Gy for 239Pu, 241Am and 233U respectively, whilst the dose to the kidney for 233U was about 0.1 Gy. 5. Autoradiographic studies of the distribution of the nuclides in the femur showed differences in their initial distribution and subsequent movement. Initially, concentrations of 239Pu were greater on endosteal than periosteal surfaces while 241Am distributed more evenly on bone surfaces. The initial deposition of 233U on all surfaces was uneven with concentrations probably on active surfaces. Burial of all three nuclides in areas of bone growth was observed. Transfer of activity to the marrow was greatest for 239Pu and least for 233U.

The postcranial skeleton of the Miocene kangaroo,Hadronomas puckridgiWoodburne (Marsupialia, Macropodidae)

Hadronomas was a large kangaroo similar in size to Simosthenurus occidentalis. Its pes was relatively long and robust, resembling those of the sthenurines Procoptodon and Sthenurus in possessing ligamentous specialisations of the fourth proximal phalanx, anteroposterior compression of fourth proximal and median phalanges, broad, blunt ‘hoof-like’ terminal fourth phalanx, a shallow calcaneocuboidal ‘step’, anteroposterior as opposed to mediolateral differentiation of the ankle joint, high, rounded profile of the astragalar trochleae and a reduced, medially situated proximal ventromedial facet of the cuboid. The upper and lower limb girdles resemble those of sthenurines in that the coracovertebral angle of the scapula is elevated and produced anteriorly in the form of a rectangular process. The innominate is anteroposteriorly broad and the ischium is flattened in cross section. The tibia possesses a sinuous shaft and an elongated, smoothly convex tibial crest that tapers gradually into the diaphysis. Hadronomas's postcranial skeleton differs from other sthenurines in retaining a large functional fifth digit and in showing no proximodistal compression of the cuboid. A character analysis of the postcranial skeleton of Hadronomas indicates that the genus represents a primitive member of the Sthenurinae, and that the Sthenurinae and the Macropodinae diverged at an early stage in macropodid evolution.

Postoperative Complications Associated with Limb Salvage for Locally Aggressive or Malignant Tumors of the Extremities and Limb Girdles

Postoperative Complications Associated with Limb Salvage for Locally Aggressive or Malignant Tumors of the Extremities and Limb Girdles

Chondroid Lipoma

We report 20 cases of a peculiar fatty tumor that occurred in 16 female and four male patients who were 14-70 years old (median, 36 years). Most lesions were situated in the subcutis, superficial muscular fascia, or skeletal muscle of the limbs and limb girdles (15), trunk (3), and the head and neck (2). They were 1.5-11 cm in size (median, 4 cm) and usually described as yellow (13 of 15) and encapsulated (13 of 15). Microscopically they were well circumscribed and consisted of nests, strands, and sheets of eosinophilic and vacuolated cells, which contained glycogen and fat droplets, resembling brown fat cells, lipoblasts and chondroblasts. In all cases there was a variable background of mature adipose tissue associated with a prominent, partially fibrinous to hyalinized myxoid matrix that contained acid mucopolysaccharides usually resistant to hyaluronidase digestion. Several cases had foci of serous atrophy, perivascular fibrosis, and small thrombi; two were focally calcified. The lesions stained for S100 protein (11 of 12), vimentin (10 of 11), and CD68 antigen with KP1 (9 of 11); focal staining for keratin was also seen (4 of 11), but none stained for epithelial membrane antigen or actin or with HMB45. Follow-up in 12 cases (median, 9.5 years) revealed no local recurrences or metastases. Despite its deep location and atypical cellular features, the lesion's nonaggressive behavior suggests it is benign and neither a myxoid liposarcoma nor a myxoid chondrosarcoma, with which it is most frequently confused. The presence of glycogen in vacuolated fat cells is similar to brown fat, and the presence of sulfated stromal mucins supports focal chondroid differentiation. Although the pathogenesis remains uncertain, a lipoma with hibernomatous features, myxoid change, chondroid metaplasia, and secondary degenerative features is favored over a lipogranulomatous process.

Clear Cell Sarcoma of Tendons and Aponeuroses

Fifty-eight previously unreported cases of clear cell sarcoma of tendons and apo neuroses occurring in 29 males and 29 females with a median age of 31 years are presented. The distal extremities were most frequently involved (58%), followed by the limbs and limb girdles (33%), and trunk (9%). Median tumor size was 2.5 cm (range, 0.6-9 cm). Kaplan-Meier estimates revealed a 5-year survival rate of 63%. Eleven of 43 patients (26%) had local recurrences at a median interval of 33 months. Metastases occurred in 20 of 45 cases (44%) at a median interval of 26 months; 19 of 20 patients with metastases died of the disease. The most common metastatic site was the lungs (11 cases), followed by bone (9 cases), and lymph nodes (8 cases). Clear cell sarcoma had a stereotypic morphology consisting of packeted arrangements of uniform, round to fusiform cells with eosinophilic to clear glycogen-rich cytoplasm, and prominent nucleoli, as well as multinucleated tumor cells with a wreath-like arrangement of nuclei. S100 protein was detected in all 44 cases studied, vimentin in 36, and HMB45 stained 36. Twenty-six cases were studied with antibodies directed against proliferating cell nuclear antigen. Neither the intensity of proliferating cell nuclear antigen staining, percentage of positive cells, nor the combined score of these two variables corresponded with mitotic rate or survival. Increasing size (as a continu ous variable) and necrosis were found to be independent adverse prognostic factors by multivariate analysis. Int J Surg Pathol 1 (2):89-100, 1993

Malignant Fibrous Histiocytoma of the Soft Tissues of the Trunk and Extremities

Malignant fibrous histiocytoma (MFH) is the most commonly diagnosed soft-tissue sarcoma. Of 408 retrospectively reviewed patients with MFH, 220 patients had primary, localized, previously untreated tumors involving the extremities or limb girdles. Univariate statistical analysis of results revealed five prognostic factors that were significantly related to poor outcome: old age, deeply seated lesions, surgical grade, large size, and marginal or intralesional surgery. Multivariate analysis revealed only three factors that were significantly related to poor prognosis: old age, deeply seated lesions, and inadequate surgery.