Malignant TFE3-rearranged perivascular epithelioid cell neoplasm (PEComa) presenting as a subcutaneous mass.

Perivascular epithelioid cell neoplasms (PEComas) are a group of mesenchymal tumours with concurrent melanocytic and myogenic differentiation. Although many cases are sporadic, PEComas can be associated with tuberous sclerosis. A distinct subset of deep-seated PEComas has been shown to carry TFE3 fusions. To our knowledge, this is the first reported case of primary subcutaneous malignant PEComa with molecular confirmation of TFE3 gene rearrangement.

Bizarre parosteal osteochondromatous proliferation (Nora's Lesion) of the mandible. a rare bony lesion.

Bizarre parosteal osteochondromatous proliferation (BPOP) also eponymically called "Nora's lesion", is a rare benign reactive bone lesion first reported in 1983. BPOP occurs classically on the bones of the hands and feet and long bones. This lesion can easily be confused, both clinically and microscopically, with other benign and malignant lesions of bone, including osteochondroma, parosteal osteosarcoma, myositis ossificans and reactive periostitis. BPOP has been reported to have a high rate of recurrence. Only 3 cases of BPOP of the head and neck have been reported in the literature, of which one involved the maxilla. We present a rare case of BPOP involving the mandible in a 10 year old African American male. Microscopically, a fibro-cartilaginous cap giving rise to a proliferation of variably mineralized osteophytic finger-like projections of bone was seen. Multiple trabeculae of "blue bone" were noted as well as numerous atypical appearing chondrocytes. The lesion recurred within 4 months following the initial excision but has not recurred to date after the second local excision. To the best of our knowledge, this is the first report of BPOP arising in the mandible. In addition, we discuss the clinical and microscopic features, differential diagnosis, and prognosis of this rare entity. We present a case of BPOP of the mandible and believe this is the first report of such a case in the mandible.

Determination of the N=16 shell closure at the oxygen drip line.

The neutron unbound ground state of (25)O (Z=8, N=17) was observed for the first time in a proton knockout reaction from a (26)F beam. A single resonance was found in the invariant mass spectrum corresponding to a neutron decay energy of 770_+20(-10) keV with a total width of 172(30) keV. The N=16 shell gap was established to be 4.86(13) MeV by the energy difference between the nu1s(1/2) and nu0d(3/2) orbitals. The neutron separation energies for (25)O agree with the calculations of the universal sd shell model interaction. This interaction incorrectly predicts an (26)O ground state that is bound to two-neutron decay by 1 MeV, leading to a discrepancy between the theoretical calculations and experiment as to the particle stability of (26)O. The observed decay width was found to be on the order of a factor of 2 larger than the calculated single-particle width using a Woods-Saxon potential.

Periosteal chondroma at birth.

Periosteal chondroma is a slow-growing, cartilaginous, surface tumor that usually occurs in the second and third decades of life. The youngest reported age at diagnosis is 5 years. Marginal excision is the treatment of choice. We report a case of a periosteal chondroma noted at birth and treated conservatively. This report expands the age range of periosteal chondroma to include neonates and suggests a role for observation in its management.

Short- and long-term prognosis for very old stroke patients. The Copenhagen Stroke Study.

BACKGROUND AND PURPOSE: The very old are expected to become a growing part of the stroke population in the industrialised part of the world. The aims of this study were to evaluate clinical characteristics of patients aged 85 years or more at stroke onset and to investigate very old age as an independent predictor of short- and long-term outcome. METHODS: In the community-based Copenhagen Stroke Study we recorded admission clinical characteristics in 1197 consecutive stroke patients. Patients were stratified according to age groups on admission. Follow-up was performed at a mean of 7 years after stroke onset. By way of multiple logistic regression and survival analyses very old age was independently related to short- and long-term mortality and nursing home placement independent of other clinical characteristics. RESULTS: 16% of patients were 85 years or older at the time of stroke onset. More of the very old were women (75% versus 50%, P<0.0001), living alone (84% versus 54%, P<0.0001), had atrial fibrillation (37% versus 15%, P<0.0001), had pre-existing disability (29% versus 22%, P = 0.04), and had more severe strokes (Scandinavian Stroke Scale score 31 versus 37 points, P = 0.004). Fewer very old had hypertension (25% versus 34%, P = 0.02) and diabetes (14% versus 22%, P = 0.01). In adjusted multiple regression models, very old age predicted short-term mortality (OR 2.5; 95% CI 1.5-4.2), and discharge to nursing home or in-hospital mortality (OR 2.7; 95% CI 1.7-4.4). Five years after stroke very old age predicted mortality or nursing home placement (OR 3.9; 95% CI 2.1-7.3), and long-term mortality (HR 2.0; 95% CI 1.6-2.5). However, other factors such as onset stroke severity, pre-existing disability and atrial fibrillation were also significant independent predictors of prognosis after stroke. CONCLUSIONS: In this study very old age per se was a strong predictor of outcome and mortality after stroke. Apart from very old age, factors such as prestroke medical and functional status, and onset stroke severity should be taken into consideration when planning treatment and rehabilitation after stroke.

Admission body temperature predicts long-term mortality after acute stroke: the Copenhagen Stroke Study.

BACKGROUND AND PURPOSE: Body temperature is considered crucial in the management of acute stroke patients. Recently hypothermia applied as a therapy for stroke has been demonstrated to be feasible and safe in acute stroke patients. In the present study, we investigated the predictive role of admission body temperature to the long-term mortality in stroke patients. METHODS: We studied 390 patients with acute stroke admitted within 6 hours from stroke onset. Admission clinical characteristics (age, sex, admission stroke severity, admission blood glucose, cardiovascular risk factor profile, and stroke subtype) were recorded for patients with hypothermia (body temperature < or =37 degrees C) versus patients with hyperthermia (body temperature >37 degrees C). Univariately the mortality rates for all patients were studied by Kaplan-Meier statistics. To find independent predictors of long-term mortality for all patients, Cox proportional-hazards models were built. We included all clinical characteristics and body temperature as a continuous variable. RESULTS: Patients with hyperthermia had more severe strokes and more frequently diabetes, whereas no difference was found for the other clinical characteristics. For all patients mortality rate at 60 months after stroke was higher for patients with hyperthermia (73 per 100 cases versus 59 per 10 cases, P=0.001). When body temperature was studied in a multivariate Cox proportional-hazards model, a 1 degrees C increase of admission body temperature independently predicted a 30% relative increase (95% CI, 4% to 57%) in long-term mortality risk. For 3-month survivors we found no association between body temperature and long-term survival when studied in a multivariate Cox proportional hazard model (hazards ratio, 1.11 per 1 degrees C; 95% CI, 0.82 to 1.52). CONCLUSION: Low body temperature on admission is considered to be an independent predictor of good short-term outcome. The present study suggests that admission body temperature seems to be a major determinant even for long-term mortality after stroke. Hypothermic therapy in the early stage in which body temperature is kept low for a longer period after ictus could be a long-lasting neuroprotective measure.

Carotid Doppler - costs and need after stroke or TIA.

OBJECTIVES: To estimate the need for and the costs of carotid Doppler and carotid endarterectomy after stroke or TIA in non-selected hospitalized patients. MATERIAL AND METHODS: During 25 months hospitalized patients with stroke or TIA, in whom carotid endarterectomy could be relevant, were examined with carotid Doppler. If a significant stenosis was found, they were further evaluated for surgery. Based on our results, the requirement for future carotid endarterectomy and Doppler screening was estimated, and the costs of the procedures calculated. RESULTS: Among 1351 patients 703 were screened with carotid Doppler. Forty-five had severe (70-99%) stenosis of the relevant carotid artery. Only 3 were operated on. The future costs of screening were estimated under different assumptions. CONCLUSION: Carotid endarterectomy is expensive due to the large number of patients screened with carotid Doppler per operated patient. A careful clinical selection of patients for screening is necessary.

Potentially reversible factors during the very acute phase of stroke and their impact on the prognosis: is there a large therapeutic potential to be explored?

In the Copenhagen Stroke Study, we evaluated the combined impact on stroke outcome of potentially treatable factors such as acute body temperature, blood glucose, and stroke in progression. The patients were stratified into two groups: (1) patients with 'good' prognostic parameters (body temperature on admission < or = 37.0 degrees C and plasma glucose on admission < or = 6.5 mmol/l and who did not develop stroke in progression) and (2) patients with correspondingly 'poor' prognostic parameters. A poor outcome was observed in 4% of the patients with good prognostic parameters versus in 49% of the patients with poor prognostic parameters (p < 0.01). In the multivariate analysis which also included stroke severity, blood glucose contributed significantly to poor outcome with an odds ratio (OR) of 1.2/1.0 mmol/l increase, body temperature with an OR of 2.2/1 degrees C increase, and stroke in progression with an OR of 2.9. However, the combined effect of all three factors was more than additive with an OR of 10.0 (95% CI 1.5-56; p < 0.01). We have shown that in human stroke a strong and more than additive association exists between potentially reversible parameters and outcome. Intervention trials can prove whether these marked relations are causal.

Immunohistochemical analysis of anaplastic lymphoma kinase expression in deep soft tissue calcifying fibrous pseudotumor: evidence of a late sclerosing stage of inflammatory myofibroblastic tumor?

Calcifying fibrous pseudotumor (CFT) is a rare benign soft tissue lesion composed of dense hyalinized fibrous tissue containing bland spindle-shaped cells admixed with a lymphoplasmacytic infiltrate and foci of dystrophic and often psammomatous calcifications. It has been suggested that CFT represents a late sclerosing stage of inflammatory myofibroblastic tumor (IMT). Recently, clonal cytogenetic abnormalities involving the anaplastic lymphoma kinase (ALK) gene on chromosome 2p have been identified in IMT, particularly those arising in deep soft tissue sites. We evaluated seven cases of deep soft tissue CFT diagnosed at the Cleveland Clinic Foundation and the University of Florida with available paraffin-embedded blocks using a monoclonal antibody to ALK (Dako, Carpenteria, CA) and a modified avidin-biotin complex method. The cohort included six women and one man with a median age at diagnosis of 43 years (range, 26 to 67 years). Sites of CFT included mesentery (3), peritoneum (1), omentum (1), serosa of small bowel (1), and anterior mediastinum (1). Immunohistochemically, only one case showed focal staining for ALK. The remaining six cases were negative, with appropriate positive and negative control staining. In conclusion, unlike IMT, CFT in deep soft tissue locations rarely expresses ALK by immunohistochemistry, suggesting that CFT is a different clinicopathologic entity than IMT, as opposed to representing a "burned out" IMT. Ann Diagn Pathol 5:10-14, 2001.

Early infection and prognosis after acute stroke: the Copenhagen Stroke Study.

BACKGROUND AND PURPOSE: Infection is a frequent complication in the early course of acute stroke and may adversely affect stroke outcome. In the present study, we investigate early infection developing in patients within 3 days of admission to the hospital and its independent relation to recovery and stroke outcome. In addition, we identify predictors for early infections, infection subtypes, and their relation to initial stroke severity. METHODS: In the community-based Copenhagen Stroke Study, 1,156 unselected patients were examined for early infection. Stroke severity was assessed with the Scandinavian Stroke Scale (SSS) on admission and at discharge. Multiple logistic and linear regression analyses were used to determine independent relations to early infection. Relevant stroke risk factors, admission stroke severity, and body temperature were included in the analysis. RESULTS: Of the subjects studied, 19.4% developed early infection. In women, 68% of the early infections were urinary tract infections, and in men, 49% of the early infections were pneumonias. Independent predictors of early infection were advanced age (OR per 10 years, 1.24; 95% CI, 1.02-1.64), female gender (OR, 2.0; 95% CI, 1.3-3.0), and decreased SSS score on admission (OR per 10 points, 0.69; 95% CI, 0.62-0.78). The presence of early infection prolonged hospital stay by a mean of 9.3 days (P < .0001) but not death during hospital stay (P = .78), stroke severity at discharge (P = .32), or rate of discharge to nursing home (P = .17). CONCLUSION: Advanced age, female gender, and increased stroke severity independently predict development of early infection. The present study indicates that early infection does not influence outcome in acute stroke patients per se, but it delays patient discharge from the hospital.

Feasibility and safety of inducing modest hypothermia in awake patients with acute stroke through surface cooling: A case-control study: the Copenhagen Stroke Study.

BACKGROUND AND PURPOSE: Hypothermia reduces neuronal damage in animal stroke models. Whether hypothermia is neuroprotective in patients with acute stroke remains to be clarified. In this case-control study, we evaluated the feasibility and safety of inducing modest hypothermia by a surface cooling method in awake patients with acute stroke. METHODS: We prospectively included 17 patients (cases) with stroke admitted within 12 hours from stoke onset (mean 3.25 hours). They were given hypothermic treatment for 6 hours by the "forced air" method, a surface cooling method that uses a cooling blanket with a flow of cool air (10 degrees C). Pethidine was given to treat compensatory shivering. Cases were compared with 56 patients (controls) from the Copenhagen Stroke Study matched for age, gender, initial stroke severity, body temperature on admission, and time from stroke onset to admission. Blood cytology, biochemistry, ECGs, and body temperature were monitored during hypothermic treatment. Multiple regression analyses on outcome were performed to examine the safety of hypothermic therapy. RESULTS: Body temperature decreased from t(0)=36.8 degrees C to t(6)=35.5 degrees C (P:<0.001), and hypothermia was present until 4 hours after therapy (t(0)=36.8 degrees C versus t(10)=36.5 degrees C; P:=0.01). Mortality at 6 months after stroke was 12% in cases versus 23% in controls (P:=0. 50). Final neurological impairment (Scandinavian Stroke Scale score at 6 months) was mean 42.4 points in cases versus 47.9 in controls (P:=0.21). Hypothermic therapy was not a predictor of poor outcome in the multivariate analyses. CONCLUSIONS: Modest hypothermia can be achieved in awake patients with acute stroke by surface cooling with the "forced air" method, in combination with pethidine to treat shivering. It was not associated with a poor outcome. We suggest a large, randomized clinical trial to test the possible beneficial effect of induced modest hypothermia in unselected patients with stroke.

Sarcomas arising in dermatofibrosarcoma protuberans: a reappraisal of biologic behavior in eighteen cases treated by wide local excision with extended clinical follow up.

There is a prevailing view that sarcomas arising in dermatofibrosarcoma protuberans (DFSP) have a higher risk of metastasis than ordinary DFSP, but these data are based on cases with variable and often suboptimal treatment. There has not been a large study of sarcomas arising in DFSP in which all cases were treated by wide local excision, thereby arguably altering outcome. Clinicopathologic features of 18 cases of sarcomas arising in DFSP treated by wide local excision and having follow up of at least 5 years were analyzed. An estimate of the proportion of sarcoma and DFSP was made. The number of mitotic figures and degree of CD34 immunoreactivity were assessed in each case. The cohort included 13 females and 5 males (age, 23-87 yrs; median, 47 yrs). The tumors involved the trunk (7), scalp (4), extremities (4), and inguinal region (3), and ranged from 1.5 to 7 cm (median, 4 cm). Sarcoma occurred de novo in 15 cases and in a recurrence in three. Sarcomas resembled fibrosarcoma (17) or malignant fibrous histiocytoma (1) and occupied between 20% and 80% of the tumor (median, 60%). Mitotic activity ranged from 2 to 16 per 10 high-power field (HPF; median 7 per 10 HPF) in the sarcomatous component and 0 to 3 per 10 HPF (median, 1 per 10 HPF) in the DFSP component. All tumors expressed CD34 in the DFSP component but only nine (50%) in the sarcomatous component. All patients were treated by wide local excision with negative margins; three additionally received radiation. Four patients (22%) developed recurrences, but none developed metastasis during the follow-up period of 62 months to 17 years (median, 81.5 mos). In contrast to earlier studies, we demonstrate that patients with sarcomas arising in DFSP do not have an increased risk of distant metastasis within a 5-year follow-up period, provided they are treated by wide local excision with negative margins. This probably reflects the fact that wide local excision results in eradication of local tumor, thereby eliminating the source for subsequent dissemination. However, we cannot completely exclude the possibility that tumors in which clear margins are achieved represent a less aggressive subset, as has been suggested for high-grade extremity sarcomas. Previous studies showing increased metastasis for sarcomas arising in DFSP should be re-evaluated to determine if, with treatment stratification, metastatic rate varies.

Extragastrointestinal (soft tissue) stromal tumors: an analysis of 48 cases with emphasis on histologic predictors of outcome.

The clinicopathologic features of 48 tumors that were histologically similar to gastrointestinal stromal tumors but occurred in the soft tissues of the abdomen were analyzed to determine their overall similarity to their gastrointestinal counterpart, their biologic behavior, and the parameters that predict risk for adverse outcome. Classic leiomyomas and leiomyosarcomas were specifically excluded. The tumors occurred in 32 women and 16 men, who ranged in age from 31 to 82 years (mean, 58 years). Forty tumors arose from the soft tissue of the abdominal cavity, and the remainder arose from the retroperitoneum. They ranged in size from 2.1 to 32.0 cm and varied from tumors composed purely of rounded epithelioid cells to those composed of short fusiform cells set in a fine fibrillary collagenous background with some cases showing a mixed pattern. Tumors displayed variable amounts of stromal hyalinization, myxoid change, and cyst formation. The tumors expressed CD117 (c-kit receptor) (100%), CD34 (50%), neuron-specific enolase (44%), smooth muscle actin (26%), desmin (4%), and S-100 protein (4%). Tumors were evaluated with respect to several parameters: size (<10 cm or >10 cm), cellularity (low or high), mitoses (0 to 2 per 50 high-power fields, >2 per 50 high-power fields), nuclear atypia (1 to 3+), cell type (epithelioid, spindled, or mixed), and necrosis (absent or present). These parameters were then evaluated in univariate and multivariate analysis with respect to adverse or nonadverse outcome, the former defined as metastasis or death from tumor. Follow-up information was obtained for 31 patients (range, 4 to 84 months; median, 24 months). One patient presented with an adverse event and, therefore, was excluded from subsequent analysis. Twelve patients (39%) developed metastases or died of tumor. In univariate analyses, cellularity, mitotic activity (>2 per 50 high-power fields), and necrosis were associated with statistically significant increases in the risk for adverse outcome. Despite the relatively small sample size, in a multivariable analysis mitotic activity (relative risk, 7.46; P = .09) and necrosis (relative risk, 3.75; P = .07) displayed trends toward independent predictive value. No association was noted between histologic pattern and outcome. Although only 39% of tumors behaved in a malignant fashion, this figure probably represents a conservative estimate because long-term follow-up (>5 years) was available for only a limited number of patients. Stratification of patients who have extragastrointestinal stromal tumor into those with 0 to 1 adverse histologic factors versus those with 2 to 3 offers the advantage of separating patients into two groups that have a markedly different risk for adverse outcome in the short term (0.02 events versus 0.54 events per person-year; P < .001, respectively). Extragastrointestinal (soft tissue) stromal tumors are histologically and immunophenotypically similar to their gastrointestinal counterpart but have an aggressive course more akin to small intestinal than gastric stromal tumors.

Dedifferentiated parosteal osteosarcoma with rhabdomyosarcomatous differentiation.

Dedifferentiated parosteal osteosarcomas are characterized histologically by the combination of low-grade fibroblastic osteosarcoma admixed with a high-grade component that typically has the appearance of malignant fibrous histiocytoma or osteosarcoma. Herein we report a case of dedifferentiated parosteal osteosarcoma of the distal femur, in which the high-grade component consisted of rhabdomyosarcoma. To our knowledge, a rhabdomyosarcomatous component has not been described previously in a dedifferentiated parosteal osteosarcoma. The clinical, radiologic, and pathologic features of this rare type of surface osteosarcoma are described.

What determines good recovery in patients with the most severe strokes? The Copenhagen Stroke Study.

BACKGROUND AND PURPOSE: Even patients with the most severe strokes sometimes experience a remarkably good recovery. We evaluated possible predictors of a good outcome to search for new therapeutic strategies. METHODS: We included the 223 patients (19%) with the most severe strokes (Scandinavian Stroke Scale score <15 points) from the 1197 unselected patients in the Copenhagen Stroke Study. Of these, 139 (62%) died in the hospital and were excluded. The 26 survivors (31%) with a good functional outcome (Barthel Index >/=50 points) were compared with the 58 survivors (69%) with a poor functional outcome (Barthel Index <50 points). The predictive value of the following factors was examined in a multivariate logistic regression model: age; sex; a spouse; work; home care before stroke; initial stroke severity; blood pressure, blood glucose, and body temperature on admission; stroke subtype; neurological impairment 1 week after onset; diabetes; hypertension; atrial fibrillation; ischemic heart disease; previous stroke; and other disabling disease. RESULTS: Decreasing age (odds ratio [OR], 0.50 per 10-year decrease; 95% CI, 0.25 to 0.99; P=0.04), a spouse (OR, 3.1; 95% CI, 1.1 to 8. 8; P=0.03), decreasing body temperature on admission (OR, 1.8 per 1 degrees C decrease; 95% CI, 1.1 to 3.1; P=0.01), and neurological recovery after 1 week (OR, 3.2 per 10-point increase in Scandinavian Stroke Scale score; 95% CI, 1.1 to 7.8; P=0.01) were all independent predictors of good functional outcome. CONCLUSIONS: Patients with the most severe strokes who achieve a good functional outcome are generally characterized by younger age, the presence of a spouse at home, and early neurological recovery. Body temperature was a strong predictor of good functional outcome and the only potentially modifiable factor. We suggest that a randomized controlled trial be undertaken to evaluate whether active reduction of body temperature can improve the generally poor prognosis of patients with the most severe strokes.

Recurrence of desmoid tumor in a multivisceral transplant patient with Gardner's syndrome.

BACKGROUND: Desmoid tumors are locally invasive fibromatous tumors, which, in patients with Gardner's syndrome, usually occur in the abdominal wall or intra-abdominally. After excision, they tend to recur, often leading to multiple bowel resections. METHODS: This is a report of the clinical course of a patient with Gardner's syndrome and desmoid tumor who had multiple enterectomies and gradually developed short-gut syndrome. He required prolonged parenteral nutrition, which damaged the liver. The patient underwent a multivisceral transplantation as a life-saving procedure. RESULTS: After the transplant, the desmoid tumor recurred in the thoracic wall twice and was successfully resected. It also recurred in the abdominal cavity, compressing the intestinal loops; the tumor was excised uneventfully, leaving the graft intact. The recurrent tumors were all of recipient origin. CONCLUSIONS: Intestinal and multivisceral transplantation could be considered in patients with short-gut syndrome caused by recurrent desmoid tumor. In the case of posttransplant tumor recurrence, resection is the only option recommended.

Retroperitoneal leiomyosarcomas unassociated with the gastrointestinal tract: a clinicopathologic analysis of 17 cases.

Data are limited on leiomyosarcomas within the abdomen and retroperitoneum, particularly if one discounts those associated with the gastrointestinal (GI) tract. Recently, some authors proposed that certain tumors in this location are more appropriately termed extra-GI stromal tumors, given their histologic resemblance to GI stromal tumors as opposed to conventional soft tissue leiomyosarcomas. We evaluated the clinical and pathologic features of 17 cases of leiomyosarcoma (16 retroperitoneal, one intra-abdominal) and recorded the tumor size, predominant cell type, tumor cellularity, nuclear pleomorphism, extent of tumor cell necrosis, and number of mitotic figures per 10 high power fields (MFs/10HPFs). Cases were only included for study if the excised tumor did not arise from abdominal or pelvic viscera or major blood vessels, if adequate clinical follow-up was available, and if the tumor unequivocally resembled conventional soft tissue leiomyosarcoma, both by light microscopic and immunohistochemical examination. The cohort included 16 women and 1 man, and ages ranged from 44 to 72 years (median, 60 yr). Tumors ranged in size from 6.5 to 29.5 cm (median, 13.5 cm). Fifteen tumors were composed predominantly of spindled cells, one tumor was composed predominantly of epithelioid cells, and one tumor was composed of an admixture of spindled and epithelioid cells. Follow-up intervals ranged from 4 to 169 months (median, 47 mo). Fifteen (88%) of seventeen patients developed an adverse outcome, defined as the development of metastatic disease or death due to tumor. Patients whose tumors had greater than 10 MFs/10HPFs had significantly shorter intervals to either metastasis or death than did those whose tumors had 10 or fewer MFs/10HPFs (8.4 mo vs. 42 mo; P = .003). No other features correlated with time to adverse outcome. In conclusion, the majority of patients with leiomyosarcomas located within the abdomen or retroperitoneum progress to metastatic disease or die from their tumor. The only feature that is significantly associated with a shorter interval to either metastasis or death is more than 10 MFs/10HPFs.