Diagnostic criteria for temporomandibular disorders: Diagnostic accuracy for general dentistry procedure without mandatory commands regarding myalgia, arthralgia and headache attributed to temporomandibular disorder.

The clinical examination in diagnostic criteria for temporomandibular disorders (DC/TMD) is a strict procedure and comprises mandatory commands. However, learning and using these mandatory commands in general practice have proven to be difficult and their use of DC/TMD is minimal. To investigate whether reliability on a diagnostic level for DC/TMD diagnoses differs between examiners using the mandatory commands or not. Six examiners were divided into two groups: one using the mandatory commands in DC/TMD for the clinical examination and one who did not use the mandatory commands. A reliability assessment was performed twice, one occasion for each group of examiners. The assessment was performed according to the guidelines from the International Network for Orofacial Pain and Related Disorders Methodology. Each group of examiners thereby examined 16 subjects (11 TMD patients and 5 healthy individuals) each, and the diagnostic agreement (reliability) as compared to diagnoses derived by a reference standard examiner was calculated with Cohen' s kappa coefficient. The DC/TMD diagnoses myalgia, arthralgia and headache attributed to TMD were included in the reliability assessment. There was no significant difference regarding diagnostic agreement reliability between the examiners using or not using the mandatory DC/TMD commands. This study indicates that not using the mandatory commands in DC/TMD in general practice does not impair the diagnostic reliability regarding the diagnoses myalgia, arthralgia and headache attributed to TMD compared to including the commands.

Safety and efficacy of oral anticoagulants in extreme weights.

BACKGROUND: The 2021 International Society on Thrombosis and Haemostasis' (ISTH) recommends standard doses of apixaban and rivaroxaban regardless of high body mass index (BMI) and weight, but had not compare DOACs head-to-head in obesity or address underweight patients. METHODS: Our aim is to evaluate the safety and efficacy of DOACs in underweight and obese patients compared to warfarin. The primary endpoints include incidence of thromboembolic and bleeding events. Descriptive statistics was used for continuous variables. The Kruskal-Wallis test was used to compare the four-groups for continuous measures and the chi-square test or Fisher's exact test was used to analyze categorical data. The chi-square test or Fisher's exact test, was used for categorical variables, and the Mann-Whitney test (the non-parametric counterpart to the two-sample t-test) for continuous data. RESULTS: Of 2940 patients receiving anticoagulation for venous thromboembolism (VTE) treatment or atrial fibrillation (AF), 492 met eligibility criteria. Within each group, 248 patients received warfarin, 101 received apixaban, 100 received rivaroxaban and 43 received dabigatran. Patients were characterized in 4 body mass index (BMI) categories, in which 80 were underweight and 412 were obese. CONCLUSIONS: When each DOAC was compared to warfarin in rates of VTE, apixaban showed statistically significant lower rate of VTE (p = 0.0149). However, no statistical significance was identified in the rate of VTE between DOACs combined vs. warfarin (p = 0.1529). When each DOAC was compared to warfarin, apixaban showed the lowest rate of overall bleeding (p = 0.0194). However, no statistical difference in the rate of bleeding was observed between DOACs combined vs. warfarin (p = 0.3284). Patients with extreme body weights requiring anticoagulation for VTE and AF may safety benefit from DOAC therapy. This evaluation showed apixaban with the lowest rate of VTE and bleeding compared to warfarin, rivaroxaban, and dabigatran. These results provide experience for the clinician to use DOACs, particularly apixaban, in underweight and obese populations.

Long term outcomes of robotic-assisted abdominal wall reconstruction: a single surgeon experience.

INTRODUCTION: Robotic abdominal wall reconstruction (RAWR) is one of the most significant advances in the management of complex abdominal wall hernias. The objective of this study was to evaluate long term outcomes in a cohort of patients that underwent complex RAWR in a single center. METHODS: This was a longitudinal retrospective review of a cohort of 56 patients who underwent complex RAWR at least 24 months prior by a single surgeon at a tertiary care institution. All patients underwent bilateral retro-rectus release (rRRR) with or without robotic transversus abdominis release (rTAR). Data collected include demographics, hernia details, operative and technical details. The prospective analysis included a post-procedure visit of at least 24 months from the index procedure with a physical examination and quality of life survey using the Carolinas Comfort Scale (CCS). Patients with reported symptoms concerning for hernia recurrence underwent radiographic imaging. Descriptive statistics (mean ± standard deviation or median) were calculated for continuous variables. Chi-square or Fisher's exact test as deemed appropriate for categorical variables, and analysis of variance or the Kruskal-Wallis test for continuous data, were performed among the separate operative groups. A total score for the CCS was calculated and analyzed in accordance with the user guidelines. RESULTS: One-hundred and-forty patients met the inclusion criteria. Fifty-six patients consented to participate in the study. Mean age was 60.2 years. Mean BMI was 34.0. Ninety percent of patients had at least one comorbidity and 52% of patients were scored ASA 3 or higher. Fifty-nine percent were initial incisional hernias, 19.6% were recurrent incisional hernias and 8.9% were recurrent ventral hernias. The mean defect width was 9 cm for rTAR and 5 cm for rRRR. The mean implanted mesh size was 945.0 cm2 for rTAR and 362.5 cm2 for rRRR. The mean length of follow-up was 28.1 months. Fifty-seven percent of patients underwent post-op imaging at an average follow-up of 23.5 months. Recurrence rate was 3.6% for all groups. There were no recurrences in patients that underwent solely bilateral rRRR. Two patients (7.7%) that underwent rTAR procedures were found with recurrence. Average time to recurrence was 23 months. Quality of life survey demonstrated an overall CCS score of 6.63 ± 13.95 at 24 months with 12 (21.4%) patients reporting mesh sensation, 20 (35.7%) reporting pain, and 13 (23.2%) reporting movement limitation. CONCLUSION: Our study contributes to the paucity of literature describing long term outcomes of RAWR. Robotic techniques offer durable repairs with acceptable quality of life metrics.

Oxalobacter formigenes treatment confers protective effects in a rat model of primary hyperoxaluria by preventing renal calcium oxalate deposition.

In primary hyperoxaluria, increased hepatic oxalate production sometimes leads to severe nephrocalcinosis and early end-stage kidney disease. Oral administration of Oxalobacter formigenes (O. formigenes), an oxalate-degrading bacterium, is thought to derive oxalate from systemic sources by inducing net enteric oxalate secretion. Here, the impact of O. formigenes on nephrocalcinosis was investigated in an ethylene glycol rat model mimicking hepatic oxalate overproduction in primary hyperoxaluria. Eighteen rats were administered ethylene glycol (0.75% in drinking water) for 6 weeks, of which 9 were treated by oral gavage with O. formigenes and 9 received vehicle. Five control rats did not receive ethylene glycol or O. formigenes. Plasma and urinary oxalate levels, calcium oxalate crystalluria, urinary volume, fluid intake, and serum creatinine were monitored during the study. On killing, nephrocalcinosis was quantified. Ethylene glycol intake induced pronounced hyperoxalemia, hyperoxaluria, calcium oxalate crystalluria and nephrocalcinosis. Concomitant O. formigenes treatment partially prevented the ethylene glycol-induced increase in plasma oxalate and completely prevented nephrocalcinosis. Urinary oxalate excretion was not reduced by O. formigenes treatment. Nevertheless, absence of crystals in renal tissue of O. formigenes-treated ethylene glycol animals indicates that the propensity for oxalate to crystallize in the kidneys was reduced compared to non-treated animals. This is supported by the lower plasma oxalate concentrations in O. formigenes-treated animals. This study shows a beneficial effect of O. formigenes treatment on ethylene glycol-induced hyperoxalemia and nephrocalcinosis, and thus supports a possible beneficial effect of O. formigenes in primary hyperoxaluria.

Effects of medications on post-endoscopic retrograde cholangiopancreatography pancreatitis.

BACKGROUND AND AIMS: Drug-induced pancreatitis accounts for about 2% of acute pancreatitis. The aim of this study is to determine whether propofol and other medications are associated with increased risk for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. METHODS: A retrospective study was conducted at a single tertiary care hospital. All patients who underwent ERCP from 2001 to 2004 were included. Diagnosis of acute post-ERCP pancreatitis was based on a consensus definition. RESULTS: A total of 506 patients underwent ERCP. The total incidence of post-ERCP pancreatitis was 7.1%. There was no significant difference in post-ERCP pancreatitis between patients who received propofol compared to patients who received midazolam and fentanyl (9.0 vs. 5.9%, p = 0.18). Patients receiving an angiotensin receptor blocker were approximately 4 times more likely to develop post-ERCP pancreatitis (OR = 4.1, 95% CI 1.6-10.9). Patients younger than 65 years and smokers also had higher risk of developing acute post-ERCP pancreatitis than those who were older than 65 years (OR = 3.9, 95% CI 1.7-9.1) and non-smokers (OR = 2.8, 95% CI 1.3-6.2). CONCLUSIONS: Propofol is a safe sedative drug for ERCP without additional risk of developing acute post-ERCP pancreatitis. Use of angiotensin receptor blockers, smoking and younger age are independent risk factors for post-ERCP pancreatitis.

Low-grade fibromyxoid sarcoma is difficult to diagnose by fine needle aspiration cytology: a cytomorphological study of eight cases.

BACKGROUND: Low-grade fibromyxoid sarcoma (LGFMS) is an uncommon neoplasm with bland morphology and an indolent clinical course, although metastases may develop in approximately 5-10% of the cases. The diagnosis of LGFMS can be difficult to render from fine needle aspiration cytology (FNAC) alone because of morphological overlap with other spindle cell and myxoid lesions. OBJECTIVE: To determine cytological criteria for LGFMS by reviewing FNAC aspirates in eight cases and to compare the findings with those in subsequent histological sections. METHODS: FNAC slides were reviewed from eight patients with subsequently excised tumours diagnosed as LGFMS. Of these patients, six also had core needle biopsies (CNB). Cytogenetic and/or molecular analysis was carried on all tumours. RESULTS: The patients were six men and two women ranging in age from 26 to 78 years. Tumours arose in the deep soft tissues of the thigh (n = 5), shoulder girdle (n = 1) or upper arm (n = 1) and one in the subcutaneous tissue of the abdominal wall. Cytological features included clusters of bland spindle and round/polygonal cells embedded in a collagenous and myxoid matrix along with dissociated, uniform or slightly/moderately pleomorphic spindle cells, bare nuclei and fragments of collagen and myxoid tissue in varying proportions. Unequivocal sarcoma was diagnosed in two aspirates, but mitoses were absent in all cases. In three cases, the diagnosis was inconclusive with regard to benignity or malignancy, while three were erroneously diagnosed as benign spindle cell lesions. Although the diagnosis was suggested on three of six CNB, these presented similar diagnostic problems. CONCLUSIONS: There were no cytomorphological findings in FNAC to allow for a clear cut separation of LGFMS from other spindle cell or myxoid lesions, but high-grade sarcoma could be excluded. Surgical (incisional or excisional) biopsy or, alternatively, examination of RT-PCR for the FUS/CREB3L or FUS/CREB3L1 fusion transcripts may be necessary to obtain a correct diagnosis.

Clinicopathologic re-evaluation of 100 malignant fibrous histiocytomas: prognostic relevance of subclassification.

PURPOSE: Malignant fibrous histiocytoma (MFH) has been regarded as the most common soft tissue sarcoma (STS) in adults. Yet its true nature and the validity of this diagnostic concept have increasingly been questioned. Available data suggest that most patients with MFH can be subclassified into specific STS types, but the clinical relevance of such categorization has been argued. In a retrospective study, we reclassified 100 tumors of the extremity and trunk wall primarily diagnosed as MFH and analyzed the outcome. PATIENTS AND METHODS: Patients were adults (median age, 70 years; range, 32 to 94 years). The median tumor size was 8 cm (range, 1 to 30 cm), and the thigh was the most common tumor location (n = 31). Median follow-up was 8 years (range, 3 to 16 years). The overall 5-year metastasis-free survival rate was 0.64. The tumors were reanalyzed histologically, immunohistochemically, and, where available, ultrastructurally, and were classified according to strict diagnostic criteria. Patients were staged according to the American Joint Committee on Cancer system, and prognoses were compared among different groups of the reclassified diagnoses, paying special attention to myogenic tumors. RESULTS: In 84 of 100 tumors, a specific line of differentiation was either proved or strongly suggested. The most common diagnoses were myxofibrosarcoma (n = 22) and leiomyosarcoma (n = 20). Overall, 30 tumors could be grouped as some form of myogenic sarcoma. These tumors had a worse prognosis, even within the same American Joint Committee on Cancer stage, and a shorter time to metastasis than nonmyogenic tumors. CONCLUSION: This retrospective study confirms that most so-called MFH can be subclassified by defined criteria; it provides evidence that such classification is clinically important. Specifically, pleomorphic STS showing myogenic differentiation are significantly more aggressive, a finding that allows planning future therapeutic trials.

Limb-sparing surgery without radiotherapy based on anatomic location of soft tissue sarcoma.

From 1980 through 1986, 119 patients with soft tissue sarcomas of the extremities were referred to our tumor center either before surgery (n = 78) or immediately after incisional biopsy or marginal excision (n = 41). The tumors were classified according to anatomic location at admittance as subcutaneous (n = 40), intramuscular (n = 30), and extramuscular tumors (n = 49). Open biopsy was omitted in 75 of the 78 patients referred before surgery; the preoperative diagnosis was based on physical and radiographic findings and fine-needle aspiration cytology. The surgical intention for subcutaneous tumor was to obtain a wide margin, which required a cuff of fat tissue around the tumor and inclusion of the deep fascia beneath the tumor. A wide margin for an intramuscular tumor implied no open biopsy and an unbroken muscle fascia or thick muscle cuff around the tumor (primary myectomy). The 70 patients with subcutaneous and intramuscular tumors were all treated by local surgery. A wide margin was obtained in 56 patients who were not given radiotherapy. During a median follow-up of 5 years (range, 3.5 to 10 years), four of these 56 patients--47 of whom had high-grade malignant tumors--had a local recurrence. We conclude that routine combination of limb-sparing surgery with adjuvant radiotherapy is not necessary in patients with soft tissue sarcoma. Two thirds of soft tissue sarcomas of the extremities are primarily subcutaneous or intramuscular tumors, the majority of which can be treated by local surgery without local adjuvant therapy with a local recurrence rate of less than 10%, irrespective of malignancy grade.

Cellular DNA content and prognosis of high-grade soft tissue sarcoma: the Scandinavian Sarcoma Group experience.

The nuclear DNA content of 148 high-grade soft tissue sarcomas of the extremities and trunk was determined by flow cytometry, using tumor material from paraffin-embedded tissue. The patients were part of a prospective randomized clinical trial on the efficacy of adjuvant single-agent chemotherapy with doxorubicin. Chemotherapy did not improve the metastasis-free survival (MFS). After a median follow-up time of 48 months (range, 2 to 97), a multivariate analysis of prognostic factors for developing metastatic disease was performed. DNA aneuploidy was found to be an independent prognostic risk factor in addition to histologic malignancy grade IV, intratumoral vascular invasion, tumor size over 10 cm, and male sex. Patients with none or one risk factor had a 5-year MFS of 79%, with two risk factors 65%, with three risk factors 43%, and with four and five risk factors 0%. About one half (78 of 148) of the patients with three factors or less belonged to a group with a MFS over 60%. The combination of different risk factors, including DNA aneuploidy, seems to be a useful prognostic model for soft tissue sarcomas, which could be of value to select high-risk patients for further trials with adjunctive therapy.

Deletion of chromosome arm 3p in hematologic malignancies.

Cytogenetic aberrations resulting in deletion of 3p are common in solid tumors, indicating the presence of tumor suppressor genes (TSG) on this chromosome arm. The present study was undertaken to investigate 3p loss in hematologic disorders. Ten acute myeloid leukemias (AML), two myelodysplastic syndromes (MDS), one Philadelphia chromosome-positive chronic myeloid leukemia (CML), three acute lymphoblastic leukemias (ALL), one chronic lymphoproliferative disorder (CLD), and three non-Hodgkin's lymphomas (NHL) with abnormalities leading to 3p deletions were identified, constituting 2.9% of AML, 0.7% of MDS, 1.0% of CML with changes in addition to t(9;22), 1.5% of ALL, 4.2% of CLD, and 1.1% of NHL with cytogenetic abnormalities analyzed at our Department. Among 19042 karyotypically aberrant published cases, 1.2% of 6260 AML, 1.3% of 2285 MDS, 0.8% of 840 chronic myeloproliferative disorders (CMD), 0.7% of 1894 CML with additional aberrations to t(9;22), 0.6% of 3589 ALL 2.4% of 1602 CLD, 4.5% of 178 Hodgkin disease (HD), and 3.1% of 2394 NHL displayed partial loss of 3p (0.6-4.5%; P < 0.001); the majority occurring together with other abnormalities. The frequencies of 3p loss did not differ significantly among the MDS, ALL, and CLD morphologic subgroups, between B and T cell ALL, CLD, and NHL, among low-, intermediate-, and high-grade NHL, or between therapy-related MDS and de novo MDS, whereas the incidence of 3p deletions was higher in treatment-associated AML (P < 0.001) than in de novo AML and varied among the AML FAB groups (P < 0.001). The most frequently deleted chromosome bands were 3p25 in AML, 3p26 in MDS, 3p14 in CMD, 3p25, 3p23, and 3p21 in CML, 3p26 and 3p25 in ALL, 3p26 and 3p25 in CLD, 3p26 in HD, and 3p26 in NHL. These deletion hot spots are more distal than those reported in most solid tumor types, suggesting that different TSG are involved in hematologic malignancies and solid neoplasms.

Mitotic activity and survival in advanced non-Hodgkin's lymphoma of unfavourable histology.

The number of mitoses per high power field (mitotic index, MI) was assessed in 2 microns sections of lymph node biopsies from 58 adults with non-Hodgkin's lymphoma. All had diffuse nodal lymphomas of unfavourable histology and stage II-IV disease. The patients were treated with chemotherapy and followed for a minimum of 3 years or until death. None out of 29 patients with a MI greater than or equal to 3.0 survived for 3 years after diagnosis whereas 13 out of 29 other patients with MI less than 3.0 became long-term survivors (P = 0.00002). Differences in age, sex or clinical stage between short- and long-term survivors were negligible. The initial chemotherapy regimens were not more intense for the long-term survivors. Twenty-nine patients were given an equivalent initial treatment with CHOP or CHOP plus methotrexate. The association between MIs and survival was evident also in this subgroup. The results indicate that survival is extremely poor for patients with advanced diffuse nodal lymphomas of unfavourable histology and a high mitotic count. It seems especially important to evaluate alternative chemotherapy regimens, suggested to be more effective than current programmes, in this subset of patients.

Five-year results in Ewing's sarcoma. The Scandinavian Sarcoma Group experience with the SSG IX protocol.

The first Scandinavian protocol for Ewing's sarcoma, SSG IV, resulted in a local control rate of 74% and 5-year metastasis-free survival (MFS) of 43%. The second protocol, SSG IX, was started in order to improve upon these results. It featured four chemotherapy cycles, each consisting of two courses of VAI (vincristine, doxorubicin, ifosfamide) alternating with one course of PAI (cisplatin, doxorubicin, ifosfamide) at 3-weekly intervals. Total treatment time was 35 weeks. Local therapy was given at week 9. Inoperable or non-radically operated patients received hyperfractionated accelerated radiotherapy 1.5 Gy twice daily between chemotherapy courses to a total dose of 42-60 Gy, depending on surgical radicality and tumour localisation. 88 patients were included (58 male, 30 female, mean age 20 years; range 5-65 years). The tumour (73 M0 and 15 M1) was located centrally in 31 patients (35%), in the extremities in 34 (39%) and other sites in 23 (26%) of cases. The median size of tumour was 10 cm (range 2-23), soft tissue was invaded in 87%. Surgery was the local therapy for 60 (68%) patients: amputation in 8 and local excision in 52. The surgical margins were wide in 35 patients, marginal in 14 and intralesional in 3. Radiotherapy was given to 17 non-radically operated patients postoperatively and to 28 patients with inoperable tumours primarily. Histological responses were evaluated in 52 patients. 9 local recurrences were observed (10%). Distant metastases developed in 24 M0 patients (33%). The estimated 5-year MFS was 58% and overall survival (OS) 70% for M0 and 27% and 28% for M1 patients, respectively. Survival was favourable in patients with non-metastatic extremity tumours (90%) and tumours operated with wide margins (90%). Patients with a total necrosis after chemotherapy had a better OS than those with a partial or poor response (P=0.003). The toxicity (World Health Organisation) was acceptable (gastrointestinal G1-2; haematological G3-4). The SSG IX protocol gave better local control and survival rates than the SSG IV. Whether this is due to a higher therapeutic efficacy of the present protocol cannot be ascertained in this comparison with a historical control.

Prognostic information in soft tissue sarcoma using tumour size, vascular invasion and microscopic tumour necrosis-the SIN-system.

We have earlier devised a system for soft tissue sarcoma (STS), based on three negative prognostic features: large tumour size, vascular invasion, and microscopic tumour necrosis, the SIN-system. Tumours which exhibit 2 or 3 of these features are categorised as high-risk, the others as low-risk. We have now tested this system for reproducibility both as regards recognition of its components, and as regards prognostic strength in patients from another institution. We have also compared it with the American Joint Committee on Cancer (AJCC) system. 200 patients with STS were analysed, all had been treated by surgery, in 97 patients combined with radiotherapy. The median follow-up for the 117 survivors was 10 (1.5-27) years. Without knowledge of the clinical data, three groups of pathologists independently reviewed original slides from all of the tumours. Based on the factors, the tumours were classified as high-risk or low-risk. The prognostic strength was compared using the results obtained by the different observers. Concordance in recognition of vascular invasion, tumour necrosis, and overall grading was seen in 156 (78%), 154 (77%), and 167 (84%) of the 200 tumours, respectively. Based on the different observers' grading, the cumulative 5-year metastasis-free survival rate (MFSR) varied for patients with low-risk tumours between 0.85 and 0.80, and for patients with high-risk tumours between 0.48 and 0.43. The Kappa-value for grading between all three groups of observers was 0.77. The SIN-system gave more clinically useful prognostic information than the AJCC system. Useful prognostic information in STS can be obtained by using tumour size, vascular invasion and microscopic tumour necrosis. This system provides two distinct prognostic groups, and has a high reproducibility.

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.

Combined morphologic and karyotypic study of 59 atypical lipomatous tumors. Evaluation of their relationship and differential diagnosis with other adipose tissue tumors (a report of the CHAMP Study Group).

Fifty-nine cases of atypical lipomatous tumors (ALT) of soft tissue (atypical lipomas, well-differentiated liposarcomas) were studied morphologically and cytogenetically as part of an international collaborative study. Forty-nine cases were deeply seated (including retroperitoneum), and 10 were superficial. Clonal chromosomal abnormalities were found in 55 cases (93%). Supernumerary ring or giant marker chromosomes (RGCs), the sole consistent alteration, were found in 37 ALTs (63%). They were more common in tumors that were large (p < 0.001), deeply seated (p < 0.005), that contained lipoblasts (p < 0.05), and that had marked cytologic atypia (p < 0.05). In a relatively short follow-up period (average, 3 years), only three of 59 cases recurred, one resulting in the patient's death. All three cases had RGCs. Also, five of the six cases that underwent dedifferentiation had RGCs, indicating that RGCs are associated not only with low-grade malignant behavior (in the form of local recurrence) but also with the potential for tumor progression. When the karyotypic profile of ALT was compared with that of 233 other types of adipose tissue tumors similarly analyzed by the authors, a statistically highly significant correlation (p < 0.0001) was found between ALT and RGCs. These results support the existence of ALT as a distinct tumor subtype that is different from ordinary lipoma and from spindle or pleomorphic lipoma, albeit histogenetically closely related to them. It also supports the proposed pathogenetic link between ALT and dedifferentiated liposarcoma. The association between chromosomal and morphologic findings indicates the potential role of karyotypic analysis in the differential diagnosis of ALT with ordinary lipoma, spindle or pleomorphic lipoma, hibernoma, and myxoid liposarcoma.

Combined morphologic and karyotypic study of 28 myxoid liposarcomas. Implications for a revised morphologic typing, (a report from the CHAMP Group).

Cytogenetic analysis carried out in 28 adipose tissue tumors diagnosed microscopically as myxoid liposarcoma (ML) revealed a t(12;16)(q13:p11) chromosomal translocation in 26 of the 28 cases. Morphologically, these tumors were subclassified into the following categories: well-differentiated, six cases: poorly differentiated round cell type, 17 cases: poorly differentiated spindle cell type, five cases. Poorly differentiated ML behaved in a more aggressive fashion than the well-differentiated tumors. The results of this study confirm the consistency and specificity of the t(12;16)(q13:p11) translocation as the genetic marker of ML, support the contention that liposarcomas with round cells belong to the ML category, and confirm Stout's proposal for the existence of a poorly differentiated ML composed of spindle cells. Cytogenetic analysis may be helpful in the differential diagnosis of ML with atypical lipomatous tumors, which is characteristically associated with ring and giant marker chromosomes, and of ML with lipoblastoma, which is typically associated with 8q alterations. The existence of a mixed ML-atypical lipomatous tumor remains questionable. The genetic events associated with the greater aggressiveness of the poorly differentiated types of ML remain to be determined.

Prognostic implications of BCL6 rearrangement in uniformly treated patients with diffuse large B-cell lymphoma--a Nordic Lymphoma Group study.

The purpose of this study was to investigate the prognostic implications of BCL6 rearrangement in a uniformly treated population of patients with diffuse large B-cell lymphoma (DLBCL) and to characterise the relationship between BCL6 rearrangement and prognostic factors. A total of 269 patients with DLBCL entered a randomised trial comparing the chemotherapy regimen CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) to the MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin) regimen. In 44 cases, frozen tissue was available for assessment of BCL6 status by Southern blot analysis. BCL6 was rearranged in six of 43 evaluable cases (14%), and was associated with elevated lactate dehydrogenase (LDH), and a higher patient age. No association between BCL6 status and expression of BCL2, Ki-67 or TP53 was found. Patients presenting with BCL6 rearrangement displayed a weak trend towards better overall and failure-free survival (67 and 67% at 5 years), compared to patients with germline BCL6 (63 and 52%), but the difference was not statistically significant. In accordance with previously published series, the presence of BCL6 rearrangement does not define a prognostically distinct subgroup of DLBCL. Assessment of BCL6 status may, however, be of clinical interest when related to other prognostic variables.

Clinical significance of genetic imbalances revealed by comparative genomic hybridization in chondrosarcomas.

DNA copy number changes were studied by comparative genomic hybridization (CGH) in 50 chondrosarcoma samples from 45 patients. Mean number of genetic aberrations in primary tumors was 4.8 +/- 1.8. The most frequently gained regions were 20q12-qter (37%), 20q (32%), 8q24.1-qter (27%), 20p (24%), and 14q24-qter (24%). Losses were 5.5 times less frequent than gains and observed mainly at Xcen-q21, 6cen-q22, and 18cen-q11.2 (11% each). Recurrent and metastatic tumors showed a mean of 4.0 +/- 2.2 aberrations per sample. The most frequently gained regions were chromosome 7 (4 cases), 5q14-q32 (4 cases), 6p (3 cases), and 12q (3 cases). Losses of DNA sequences were 3.4 times less frequent than gains. Histological tumor grade was significantly associated with metastasis-free survival (P = .002) and overall survival (P = .003), being the strongest prognostic factor tested. A statistically significant correlation was found between gain at 8q24.1-qter and shorter overall survival (P = .01) but not with local recurrence or metastasis-free survival. Gain at 14q24-qter was associated with a trend to shorter overall survival (P = .05) but neither with an increased risk for local recurrence nor with metastasis-free survival. In a multivariate analysis, only the tumor grade associated with overall survival (P = .02). In a multivariate analysis together with the tumor grade, gain at 8q24.1-qter did not retain its significance (P = .44), indicating that this imbalance is not an independent prognostic factor.

Immunohistochemical examination of 25 cases of Merkel cell carcinoma: a comparison with small cell carcinoma of the lung and oesophagus, and a review of the literature.

Merkel cell carcinomas (MCC) were compared to small cell carcinomas of the lung (SCCL) and oesophagus (SCCO). Most MCC were of the intermediate cell type while SCCL and SCCO were usually of the small cell type. Only MCC of trabecular type could be separated from SCCL and SCCO by means of histopathological examination alone. All MCC (25) stained with cytokeratin CAM 5.2, 20 of which in a "paranuclear globular" or combined "paranuclear globular"/diffuse pattern while 17 MCC stained with cytokeratin AE1/AE3. Cytokeratin CAM 5.2 reacted with 60 percent of the SCCL and 86 percent of the SCCO, and cytokeratin AE1/AE3 with 33 and 28 percent respectively. Neurofilament stained 17 MCC in a "paranuclear globular" pattern but none of the SCCL and SCCO. All MCC with a diffuse staining pattern for cytokeratin CAM 5.2 were negative for neurofilament. The results of this study and review of the literature indicate that in most instances Merkel cell carcinoma can be separated from other SCC, pulmonary as well as extrapulmonary, by means of histopathological and, above all, immunohistochemical examinations.

Expression of proliferating cell nuclear antigen (PCNA) and Ki-67 in soft tissue sarcoma. Is prognostic significance histotype-specific?

Abnormal patterns of proliferation characterize the behavior of many tumors. Proliferating cell nuclear antigen (PCNA) and Ki-67 are two cell cycle antigens which are expressed in proliferative states. Our study examines the prognostic value of these cell-cycle antigens in soft tissue sarcoma (STS). Paraffin-embedded primary tumor tissues from 185 patients (1980-92) were stained with the anti-PCNA antibody PC-10; 182 of these were stained with the antibody MIB-1 for Ki-67. Using PCNA (< or = 50; > 50%) and Ki-67 (< or = 10; > 10%) indices, we examined and compared metastasis-free survival (MFS) in a mixed-histotype group, as well as after subdivision into MFH and non-MFH groups. Fifty-seven patients developed metastases. The median follow-up for survivors was 6 (2-13) years. In the mixed series, the 2-year MFS for a PCNA index < or = 50 was 76%, and for an index > 50 56%. Survival predicted by Ki-67 index was comparable. PCNA index (but not Ki-67) strongly correlated with the incidence of metastasis in MFH tumors and predicted 2-year MFS of 81 vs 48%. In contrast, Ki-67 index (but not PCNA) strongly correlated with metastasis in non-MFH tumors and predicted 2-year MFS survival of 90 vs 45%. No correlation existed between PCNA and Ki-67 indices in the mixed histotype, MFH or non-MFH groups. In combination, a high PCNA and Ki-67 index correlated with poor survival, a high PCNA and lower Ki-67 index (or vice versa) with an intermediate survival, and low PCNA and Ki-67 indices with the best survival. The pattern of PCNA and Ki-67 expression raises the possibility of histotype specificity.