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PubMedDate not supplied

Teratoma with malignant transformation: experiences of the cooperative GPOH protocols MAKEI 83/86/89/96.

BACKGROUND: The designation of a teratoma with malignant transformation (TMT) refers to the occurrence of somatic non-germ cell malignancies within a teratoma. While TMT is a rare but well recognised phenomenon in adult germ cell tumors (GCT), data on TMT in pediatric GCTs are lacking. PATIENTS AND METHODS: Between 1982 and 2003, 641 patients with extracranial nontesticular pure teratoma (256 coccygeal, 246 ovarian, 139 other sites) were reported to the MAKEI protocols 83/86/89/96 by various, mainly German centres. Patients with teratoma and somatic malignancy were identified by database queries. Patients with malignant germ cell tumor components were excluded from this analysis. The clinical files were reviewed and re-evaluated centrally. Information was actualized by requisition to the participating hospitals. RESULTS: We identified nine patients (all female, age 0-39 years) meeting the histological criteria of TMT. Two patients had coccygeal teratomas and seven ovarian tumors. Carcinoma was the dominating malignancy (five of nine cases). Tumors with glial differentiation and embryonal tumors occurred in two cases each. Resection was performed in seven patients (including both coccygeal tumors) and adjuvant chemotherapy was administered in one of them. Two patients relapsed after resection, but both were cured with chemotherapy. Two patients suffered from advanced tumors and both were treated with primary chemotherapy. One patient was cured from the malignant component (astrocytoma), but the teratomatous components persisted. The other patient died as a result of progression of her malignant medulloepithelioma. CONCLUSIONS: Malignant transformation of pure teratomas constitutes a very rare entity in children and adolescents that is most commonly observed in postpubertal girls with ovarian teratoma. Compared to adult patients, similar malignant entities can be observed in association with teratoma. However, in our series, no sarcoma was diagnosed. In localised tumors, complete resection appears to be adequate, whereas chemotherapy should be considered in patients with R1- or R2-resection. Cisplatinum-based chemotherapy was effective as two of four relapsed patients survived tumor free. However, the ideal regimen has not yet been established and the known sensitivity of the histologic components to cytostatic drugs has to be considered in the choice of treatment. Further molecular biologic studies are necessary to understand the origin of these tumors.

Adolescent↗

PubMed2001

Thyroid cytology and the risk of malignancy in thyroid nodules: importance of nuclear atypia in indeterminate specimens.

Fine needle aspiration (FNA) cytology is the best test for malignancy in thyroid nodules. However, cytologic interpretation of FNA specimens is often difficult, especially in the presence of indeterminate microfollicular cytologic patterns, which are thought to suggest follicular neoplasm (adenoma or carcinoma). To assess the risk of malignancy associated with specific cytologic patterns, we correlated preoperative FNA cytologic patterns (n = 484 reports including repeat aspirations) with final histological diagnoses for 368 surgical thyroid specimens obtained during the period 1994-1998. The overall prevalence of malignancy in the surgical specimens was 31% (113 cancers, including 96 papillary and 9 follicular carcinomas). For nodules with benign FNA cytologic diagnoses of nodular goiter and chronic thyroiditis there was a low risk of malignancy (6/99, or 6.1%). Nodules with indeterminate cytologic patterns in the absence of nuclear atypia (i.e., microfollicles without nuclear atypia) had a similarly low malignancy risk (3/46, or 6.5%). In contrast, 31/52 nodules with cytologic nuclear atypia consistent with follicular neoplasm were malignant (60%), including specimens with or without microfollicular cytology. Nodules with frankly malignant cytologic patterns were almost invariably cancer (54/55), and cytologic diagnoses of papillary carcinoma were confirmed at surgery in all 49 cases. These results indicate that indeterminate microfollicular cytologic patterns in the absence of nuclear atypia are associated with a low risk of malignancy, at least in this series. This finding suggests that many nodules with such microfollicular cytology might be managed conservatively with observation. In contrast, cytologic nuclear atypia consistent with a follicular neoplasm confers a high risk of cancer. In addition, frankly malignant cytologic diagnoses, especially papillary carcinoma, are highly reliable, and thus may be used as a guide for planning surgery appropriate for thyroid cancer.

Adenocarcinoma, Follicular↗

PubMed2004

Thyroid nodule shape and prediction of malignancy.

BACKGROUND: Thyroid nodules are common; the vast majority benign. Preoperative determination of malignancy remains imprecise, despite fine-needle aspiration (FNA). Numerous risk factors have been proposed for predicting malignancy, though few have been found useful. Oxygen delivery is a crucial component for tumor cell growth. It has been hypothesized that malignant tumors may configure their shape to maximize access to local nutrient delivery. Mathematically, surface area to volume is maximized by a spherical shape. We sought to determine if spherical shape is a predictor of malignancy. METHODS: Seven hundred forty-seven consecutive patients underwent ultrasound evaluation and FNA of 993 solid thyroid nodules (< 25% cystic) between 1995 and 2000 and were retrospectively analyzed. Nodules were classified as benign or malignant based on FNA and/or surgical pathology. Spherical shape was estimated by calculating a ratio of the longest to shortest dimensions, and rate of malignancy correlated. RESULTS: Spherical shape was independently correlated with risk of malignancy (p < 0.001). Thyroid cancer was detected in 11% of all nodules, but ranged from 18% in spherical nodules to 5% in those least spherical. Nodules found to have suspicious or intermediate cytology showed similar variation in malignant risk. A long to short axis ratio greater than 2.5 was 100% predictive of a benign process, although present in only 4% of our cohort. A prospective validation was performed and confirmed consistent results (p < 0.01). CONCLUSION: Spherical shape is associated with an increased rate of malignancy in solid thyroid nodules. Determination of shape may assist in clinical risk assessment of thyroid cancer.

Adult↗

PubMed1997

Protection against induction of mouse skin papillomas with low and high risk of conversion to malignancy by green tea polyphenols.

We earlier showed that a polyphenolic fraction isolated from green tea (GTP) affords protection against tumor promotion and tumor progression in SENCAR mouse skin. The present study was designed to further evaluate the protective effect of GTP against the induction and subsequent progression of papillomas to squamous cell carcinomas (SCCs) in experimental protocols where papillomas were developed with a low or high probability of their malignant conversion. Topical application of GTP (6 mg/animal) 30 min prior to that of 12-O-tetradecanoylphorbol-13-acetate (TPA) either once a week for 5 weeks (high risk TPA protocol) or once a week for 20 weeks (low risk TPA protocol) or mezerein (MEZ) twice a week for 20 weeks (high risk MEZ protocol) in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated mouse skin resulted in significant protection against skin tumor promotion in terms of tumor incidence (32-60%), multiplicity (49-63%) and tumor volume/mouse (73-90%) at the termination of the experiment at 20 weeks. In three separate malignant progression experiments when papilloma yield in DMBA-initiated and TPA or MEZ promoted low and high risk protocols was stabilized at 20 weeks, animals were divided into two subgroups. These animals were either topically treated twice weekly with acetone (0.2 ml/animal, spontaneous malignant conversion group) or with GTP (6 mg/animal in 0.2 ml acetone) for an additional period of 31 weeks. During these treatment regimens, all suspected carcinomas were recorded and each one was verified histopathologically either at the time when tumor-bearing mouse died/moribund or at the termination of the experiment at 51 weeks. GTP resulted in significant protection against the malignant conversion of papillomas to SCC in all the protocols employed. At the termination of the experiment at 51 weeks, these protective effects were evident in terms of mice with carcinomas (35-41%), carcinomas per mouse (47-55%) and percent malignant conversion of papillomas to carcinomas (47-58%). The kinetics of malignant conversion suggest that a subset of papillomas formed in the early phase of tumor promotion in all the protocols had a higher probability of malignant conversion into SCCs because all the positive control groups (acetone treated) produced nearly the same number of carcinomas (33-38 in a group of 20 animals) at the end of the progression period. In the GTP-treated group of animals the number of carcinomas formed was less (14-20 in a group of 20 animals), which shows the ability of GTP to protect against the malignant conversion of papillomas of higher probability of malignant conversion to SCCs. The results of this study suggest that irrespective of the risk involved, GTP may be highly useful in affording protection against skin cancer risk.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed2005

Incidence of multiple primary malignancies in a cohort of adult patients with soft tissue sarcoma.

OBJECTIVE: Some studies to date have suggested the development of multiple primary malignancies in patients with soft tissue sarcoma. The current study was performed to quantify the risk of development of multiple primary malignancies in adult patients with soft tissue sarcoma. METHODS: A total of 406 consecutive patients who were diagnosed with soft tissue sarcoma were identified in the study analysis. The cumulative incidence of multiple malignancies was calculated by comparing Kaplan-Meier curves and log-rank tests from each histological type. A Cox proportional hazards model was used to estimate the influence on the hazard ratio (HR) of each variable. RESULTS: A total of 35 patients with soft tissue sarcoma (9%), having preceding (n = 15) and subsequent (n = 20) malignancies other than soft tissue sarcoma were documented. The 5- and 10-year estimated cumulative incidence of multiple primary malignancies were 7.6 and 12.3%, respectively. The hazard risk of multiple primary malignancies adjusted for potential confounding variables was significantly associated with age at diagnosis (HR = 1.51, P = 0.0019). The risk of multiple primary malignancies was also increased in patients with myxofibrosarcoma adjusted by the potential confounding variables (HR = 2.34, P = 0.048). The 5- and 10-year estimated cumulative incidence of multiple primary malignancies in patients with myxofibrosarcoma were both 16.9%. CONCLUSION: The results of our study confirm that the risk of multiple malignancies appears to be impacted by age at the time of diagnosis of the first tumor and by the histological type of myxofibrosarcoma.

Adult↗

PubMed2000

Is there an association of malignancy with systemic lupus erythematosus? An analysis of 276 patients under long-term review.

OBJECTIVE: To estimate the risk of malignancy in a UK cohort of patients with systemic lupus erythematosus (SLE) under long-term review. METHOD: The University College London Lupus Clinic Database was used to identify a cohort of 276 patients followed up prospectively between 1978 and 1999. Standardized incidence ratios and 95% confidence intervals for all cancers were calculated using age and sex-specific cancer incidence rates for the southeast of England. RESULTS: In total, 16 malignancies were diagnosed in 15 patients. However, five malignancies were diagnosed before the diagnosis of SLE and were therefore excluded from the final statistical analysis. One case of basal cell carcinoma was also identified, but this was also excluded from the final analysis as no comparable figures were available for the general population. Death as a direct consequence of the malignancy occurred in six (2.3%) patients, accounting for 22.6% of the deaths in our cohort of SLE patients. Compared with the general population, the overall estimated risk for all cancers was not increased in the lupus cohort (standardized incidence rate 1.16 (95% confidence interval 0.55-2. 13). Hodgkin's lymphoma was the only individual cancer that was increased in our cohort of patients [standardized incidence rate 17. 82 (95% confidence interval 0.45-99.23)]. CONCLUSIONS: In our cohort of patients with SLE we did not show an overall increased risk of malignancy. However, SLE was associated with an increased risk of Hodgkin's lymphoma compared with the general population. From our cohort of 276 patients, none of those treated with cyclosporin (3%) developed malignancy, and out of 49 (18%) patients treated with cyclophosphamide only one patient developed malignancy. Out of the 10 patients in the final analysis who developed malignancy, six had treatment with prednisolone, four with azathioprine, five with hydroxychloroquine and only one with cyclophosphamide. No statistical difference in the above cytotoxic therapy was observed between those patients who developed malignancy and those who did not.

Adult↗

PubMed1985

Association between mediastinal germ cell tumors and hematologic malignancies. Report of two cases and review of the literature.

A hematologic malignancy occurred simultaneously with a malignant mediastinal germ cell tumor in two men. In one instance the blood disorder was acute nonlymphocytic leukemia, and in the other, malignant histiocytosis. We subsequently identified nine additional patients, all male (age range 12-48 years), with a mediastinal germ cell tumor and either acute nonlymphocytic leukemia or malignant histiocytosis. Six of the 11 patients had not received either radiation or chemotherapy before development of the hematologic malignancy. One patient developed malignant histiocytosis and was found to have a malignant mediastinal germ cell tumor after having received steroid therapy for a renal allograft. The four remaining patients developed acute nonlymphocytic leukemia 5-32 months after initiation of irradiation or chemotherapy for a mediastinal germ cell tumor. In four patients with acute leukemia, karyotypic analysis established the clonal nature of the leukemic process. Although the leukemia may be therapy-related in four or possibly five patients, this explanation cannot be applied to the remaining six patients. These six patients, coupled with studies of in vitro growth characteristics of teratocarcinoma cells described previously, suggest that a previously unrecognized association between malignant mediastinal germ cell tumors and hematologic malignancies may exist in humans.

Adult↗

PubMed1995

Cystic duct patency in malignant obstructive jaundice. An ERCP-based study relevant to the role of laparoscopic cholecystojejunostomy.

OBJECTIVE: This endoscopic retrograde cholangiopancreatography-(ERCP)based study estimates the potential role of laparoscopic cholecystojejunostomy for palliation of patients with malignant obstructive jaundice. SUMMARY BACKGROUND DATA: Traditional treatment of malignant obstructive jaundice has used a standard bilioenteric anastomosis. Laparoscopic biliary bypass via a gallbladder conduit currently is an established technique; it provides a low initial morbidity alternative to open procedures, similar to endoscopic stenting. No study has specifically addressed anatomic factors relevant to cholecystojejunostomy, such as prior cholecystectomy, stricture location in reference to the hepatocystic junction, and cystic duct patency in patients with malignant obstructive jaundice. METHODS: Retrograde cholangiograms were reviewed from consecutive patients with malignant obstructive jaundice and a control group without biliary disease who underwent ERCP during a 2-year period. Patients with either prior biliary surgery or hilar tumors were excluded. The presence of gallbladder or cystic duct filling was assessed. In patients with patent cystic ducts, the distance from obstruction to the cystic duct takeoff was classified as either greater or less than 1 cm. RESULTS: Nearly half the patients with malignant obstructive jaundice were ineligible for cholecystojejunostomies because of prior biliary surgery (29%) or hilar tumors (17%). Half (50 of 101) of the remaining potential candidates had patent hepatocystic junctions. Patients with ampullary carcinoma and patent hepatocystic junctions (5 of 9) were all ideal candidates for cholecystojejunostomies, having biliary obstruction more than 1 cm from the cystic duct takeoff. Two thirds of the remaining eligible patients (28 of 45) had obstructions less than 1 cm from patent hepatocystic junctions. CONCLUSIONS: Palliation of malignant obstructive jaundice by laparoscopic cholecystojejunostomy should only be attempted after direct cholangiography demonstrates a patent hepatocystic junction that is well separated from the malignant stricture. The majority of patients with malignant obstructive jaundice are ineligible for cholecystojejunostomies because of prior cholecystectomies, hilar obstructions, or tumor involvement of the hepatocystic junction. Nonoperative treatments will continue to be indicated for the majority of patients with malignant obstructive jaundice.

Aged↗

PubMed1998

Inhibition of tissue angiotensin converting enzyme activity prevents malignant hypertension in TGR(mREN2)27.

BACKGROUND: Activation of the renin-angiotensin system has been implicated strongly in the transition from benign to malignant hypertension. However, the concomitant rise in blood pressure might also have a direct effect on the vascular wall by initiating fibrinoid necrosis and myointimal proliferation. Ascertaining the relative importance of these two factors in this process has proved difficult. TGR(mREN2)27 heterozygotes (HanRen2/Edin- -) have previously been shown to develop malignant hypertension spontaneously and exhibit the characteristic features of human malignant hypertension. OBJECTIVE: Tissue renin-angtiotensin systems have been implicated in the pathogenesis of malignant hypertension. We set out to determine whether inhibition of this system might protect against development of the disease in a rat model. METHOD: Male TGR(mREN2)27 heterozygotes (n = 24) were given a non-hypotensive dose of the angiotensin converting enzyme inhibitor ramipril (5 microg/kg per day) from 28 to 120 days of age, untreated rats acting as controls (n = 40). The incidences of malignant hypertension were compared. Systolic blood pressure was measured by tail-cuff plethysmography during treatment; tissue and plasma angiotensin converting enzyme levels and renal histological changes were assessed at the end of the treatment period or upon development of malignant hypertension. RESULTS: Sixty-three per cent of control rats and 4% of angiotensin converting enzyme inhibitor-treated rats had developed malignant hypertension by 120 days despite there having been no significant difference in systolic blood pressure throughout the course of treatment. Angiotensin converting enzyme activities in kidney, heart and resistance vessels, though not that in plasma, were significantly lower in the treated rats. The degree of medial wall thickening did not differ between the two groups whereas evidence of tissue injury (e.g. intimal fibrosis, fibrinoid necrosis and nephron injury) was significantly less common among rats in the angiotensin converting enzyme inhibitor-treated group. CONCLUSIONS: Tissue angiotensin converting enzyme inhibition at a non-hypotensive dose almost completely prevented mortality from malignant hypertension and significantly reduced tissue injury in this model, implicating angiotensin II rather than high blood pressure as the principal 'vasculotoxic' agent in malignant hypertension.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2001

Sensitivity and positive predictive values of presurgical clinical diagnosis of excised benign and malignant skin tumors: a prospective study of 835 lesions in 778 patients.

This article reports on the sensitivity and positive predictive value of clinical diagnosis of benign and malignant skin tumors by expert plastic surgeons in an Israeli clinic. Most published reports have focused on the sensitivity of clinicians' diagnoses, a general measure of the physician's skill that does not predict the rate of accuracy of a physician's diagnoses. Our study of 835 lesions in 778 patients, one of the largest Israeli series, assesses the clinical diagnosis of malignant and benign skin tumors and is one of the few that provide information on the positive predictive value, the measure that is of interest to both physicians and patients. The majority of tumors were benign (56.8 percent), 31.6 percent were malignant, and 11.6 percent were premalignant. Among the 474 benign lesions, 46 percent were nevi. The most common nevi subclass was compound nevi (53 percent), 9 percent of the nevi were dysplastic, and 5 percent were blue nevi. The most common malignant tumor was basal cell carcinoma, accounting for 78 percent of malignant tumors. Although sensitivity for clinical diagnosis of malignancy was 91.3 percent, the positive predictive value for clinical diagnosis of malignancy was 71.3 percent. The sensitivity rate for clinically diagnosing premalignant tumors was 42.3 percent, whereas the positive predictive value for these diagnoses was higher (64.1 percent). The sensitivity rate for diagnosis of all benign lesions was 85.9 percent, and the positive predictive value was 94.2 percent. The sensitivity rate for diagnosis of all nevi was 87.6 percent, and the positive predictive value was 85.7 percent: i.e., only seven of the 218 pathologically proven diagnoses of nevi (3.2 percent) were falsely diagnosed as malignant lesions. Even more interestingly, five of the 223 clinical diagnoses of nevi (2.2 percent) were pathologically proven to be malignant melanomas, and seven were found to be premalignant lesions (3.1 percent). It was concluded that publications which report only on the sensitivity neglect to provide information of interest regarding the positive predictive value. Often, positive predictive value is qualitatively different from the sensitivity, and thus relying only on the sensitivity may lead to incorrect evaluation of a clinical judgment, which may result in erroneous surgical decisions.

Adolescent↗

PubMed1995

Can we distinguish between benign versus malignant compression fractures of the spine by magnetic resonance imaging?

STUDY DESIGN: The authors investigate the usefulness of magnetic resonance imaging in differentiating benign versus malignant compression fractures by reviewing patients and a fracture model in a canine model. OBJECTIVES: To determine the sensitivity and specificity of magnetic resonance imaging in differentiating benign versus malignant compression fractures of the spine and to obtain distinguishing features in magnetic resonance imaging. SUMMARY OF BACKGROUND DATA: The differentiation between benign and abnormal compression fractures of the thoracolumbar spine has important implications regarding patient treatment and prognosis. Plain radiographs, bone scans, and computed tomography are not accurate imaging modalities for this purpose. METHODS: Magnetic resonance imaging scans of 22 patients with confirmed lesions of the thoracolumbar spine were studied. There were 11 malignant and 11 benign lesions. Two experienced neuroradiologists blindly reviewed the magnetic resonance imaging scans and determined benign or malignant lesions. A canine study was performed to simulate a compression fracture model with a vertebral osteotomy in two dogs, and serial contrast-enhanced magnetic resonance imaging scans were performed 15, 30, 60 and 90 days after surgery. RESULTS: The correct interpretation between two neuroradiologists was 77% and 95%. The combined sensitivity rate was 88.5%, and the specificity rate was 89.5%. Magnetic resonance imaging reliably distinguished benign versus malignant lesions based on the anatomic distribution and intensity of signal changes of bone and adjacent tissues, contrast enhancement characteristics, and changes over time. Only one malignant lesion was misinterpreted by both neuroradiologists as benign, whereas there was one additional missed malignant lesion and three misinterpreted benign lesions by one radiologist. In the canine study, signal changes and enhancement were found 60 days after surgery, but no signal changes or enhancement were noted on the scan 90 days after surgery. CONCLUSIONS: Magnetic resonance imaging scans can detect malignant vertebral lesions early, but acute healing compression fractures may mimic the findings of metastatic lesions. The use of contrast-enhanced magnetic resonance imaging scans and serial magnetic resonance imagings are helpful for additional differentiation between benign and malignant compression fractures. In addition to magnetic resonance imaging scans, other diagnostic tests and clinical findings should be correlated before biopsy or surgery of the suspected lesion.

Adult↗

PubMed2002

Risk for tumor and other disease transmission by transplantation: a population-based study of unrecognized malignancies and other diseases in organ donors.

BACKGROUND: Organ donation may involve the risk of transmittal of unwanted host factors such as infections and malignancy. These may be concealed in the emergent donation process. It may be unavoidable if first observed in a donor postmortem. A number of reports on transferred cancers have been published, but quantification of the risk has never been reliably performed. We report here the first population-based analysis of unrecognized malignancies and other diseases in cadaveric or living-related donors and the possible consequences for the recipients. METHODS: We compiled a cohort of all organ donors through 27 years (1969-1996) in one single kidney transplant center covering a population on one million people. This cohort was linked to the Danish Cancer Registry, the Danish National Hospital Register, and the Danish Register of Causes of Death by means of the unique personal identification number, and all cancers, diagnosis from hospital admissions, and causes of death were identified. Follow-up was to the end of 1996. RESULTS: A total of 626 donors (491 cadaveric and 135 living-related donors) was included in the study. Ten carcinoma in situ or dysplasia cervix uteri (by definition nonmalignant), and 13 malignant tumors (5 of these were detected in living-related donors after donation) were detected by linkage to the cancer registry. All together, 17 recipients received organs from donors with carcinoma in situ or dysplasia cervix uteri and 20 from donors with malignancies. Two recipients from organ donors with carcinoma in situ or dysplasia of the cervix uteri and two recipients from donors with malignancies had a cancer detected; however, these were likely unrelated. One died 1 year after transplantation from a melanoma transmitted from the donor. Two cadaveric donors had previous admissions for glomerulonephritis, five for pyelonephritis, five for nephrolithiasis or ureterolithiasis, four for cystitis, and one for hydronephrosis. CONCLUSION: Despite all efforts to secure a safe organ for transplantation, transmission of donor malignancy and other diseases nevertheless can happen, as is recorded many times in the literature. We have quantified the risk using the population-based cancer registry and found a risk of 8 in 626 (1.3%) for having a donor with undetected malignancy and a risk of 1 in 626 (0.2%) for transmitting a cancer. The risk for getting some transmitted glomerulonephritis is 2 in 626 (0.3%). None of the donors with cerebral malignancies transmitted any tumors to the recipients. Compared with the benefits of organ transplantation, these risks are small; however, if time allows, a search for additional medical information from registries could further minimize the risk of transmission of malignancies or other diseases. However, this requires updated, accurate, and accessible registries and legislation that allows access to personal data and transmission of such data across administrative borders.

Humans↗

PubMedDate not supplied

Wounds and malignancy.

Due to the prevalence of skin cancers, health care practitioners involved with wound management are likely to encounter cutaneous malignancies as part of their practice. This article focuses on 2 ways in which malignancies and wounds are related: the malignant degeneration of chronic wounds into cancer and malignancies that present as chronic wounds. The most common scenario in which chronic wounds have been associated with the development of squamous cell carcinoma is in the presence of chronic osteomyelitis. However, wounds secondary to burns, trauma, radiotherapy, and diabetes are also at risk for malignant degeneration. It is often difficult to distinguish malignant transformations from primary malignant ulcers. Given the uncommon nature of degeneration of a chronic wound or a malignancy presenting as a chronic wound, some suggest that only suspicious wounds undergo biopsy. Primary malignancy should be considered if the ulcer has a relatively short duration and the patient does not have a history of prior radiotherapy. Until recently, amputation has been the treatment of choice for squamous cell carcinomas that arose within chronic wounds associated with chronic osteomyelitis; however, other reports have shown that other methods of ensuring complete local excision are also useful.

Basal Cell Carcinoma↗

PubMed2002

Increased p53 protein expression in malignant mammary phyllodes tumors.

The authors reviewed 143 cases (87 benign, 37 borderline, and 19 malignant) of mammary phyllodes tumors (PTs) and used immunohistochemistry to detect p53 protein product semi-quantitatively as negative, weak, moderate and strong (scored 0 to 3). For all PTs, an increasing trend of tumor size and malignancy was detected with increasing age. For p53 staining, 60 cases (42%) were negative, 55 (38%) stained weakly, 28 (13%) stained moderately, and 10 (7%) stained strongly. Of the 87 benign PTs, 41 (47%) were negative, 37 (43%) stained weakly, and 9 (10%) stained moderately. For the 37 borderline PTs, 16 (43%) were negative, 14 (38%) stained weakly, 6 (16%) stained moderately, and 1 (3%) stained strongly. Of the 19 malignant PTs, 3 (16%) were negative, 4 (21%) stained weakly, 3 (16%) stained moderately, and 9 (47%) stained strongly. The mean intensity score for p53 staining increased progressively from benign to borderline to malignant PT, with established statistical significance (P <.0001). This is significantly correlated with mitotic count but not stromal cellularity, pleomorphism, margin, and stromal overgrowth. When considering strong staining alone (score, 3), 47% of malignant, 3% of borderline, and none of the benign PTs were positive. The use of strong positive staining for diagnosing malignant PT gave positive and negative predictive values, specificity, and sensitivity of 90%, 92.5%, 99%, and 47%, respectively. Thus diffuse strong p53 protein staining can be used as a soft sign in assisting the diagnosis of malignant PT. Conversely, negative or weak staining of p53 protein in PT is of little discriminatory value. The role of p53 gene mutation in the malignant transformation of PT is unclear; but this may not be the sole mechanism as many malignant PT were p53 protein negative.

Adolescent↗

PubMed2005

Risk of malignant transformation of congenital melanocytic nevi: a retrospective nationwide study from The Netherlands.

PURPOSE: Since the risk of malignant transformation is the most important reason to remove congenital melanocytic nevi, and data vary in the literature, we aimed to determine the incidence of malignant transformation in congenital melanocytic nevi in The Netherlands. METHODS: The Dutch nationwide pathology database, PALGA (Pathologisch Anatomisch Landelijk Geautomatiseerd Archief), provided anonymous pathology descriptions of all patients registered with congenital melanocytic nevi (giant or nongiant nevus) and of patients with a malignant melanoma within a congenital melanocytic nevus who were diagnosed between January 1, 1989, and December 31, 2000. A comparison was made between cancer incidence in our cohort of patients and the general population by applying the person-year distribution in the cohort to sex-, age- and calendar period-specific reference data obtained from The Netherlands Cancer Registry. Our cohort consisted of 3929 patients. RESULTS: After a median follow-up time of 4.7 years, a total of 15 cases of malignant melanoma were observed in 19,253 person-years, against 1.23 expected cases. The incidence rate of malignant melanoma was greater than expected on the basis of population rates, overall standardized incidence rate of 12.2 (95 percent confidence interval 9.6 to 15.3). Compared with the general population rates, we observed an increased risk for malignant melanoma, both in men (standardized incidence ratio = 6.4; 95 percent confidence interval 4.1 to 9.6) and women (standardized incidence ratio = 14.1; 95 percent confidence interval 10.5 to 18.7). This is comparable with the higher propensity of women to develop a malignant melanoma. Patients with a giant nevus had a 51.6 percent higher risk of developing a malignant melanoma compared with the general population rates. CONCLUSION: Our study shows that congenital melanocytic nevi have a significantly higher risk of developing a malignant melanoma compared with the age-, sex-, calendar-period-specific reference data from The Netherlands Cancer Registry.

Adult↗

PubMed2005

Maintenance immunosuppression with target-of-rapamycin inhibitors is associated with a reduced incidence of de novo malignancies.

BACKGROUND: Immunosuppressive drug therapy has been identified as one etiological factor in the increased incidence of and deaths from malignancies in renal transplant recipients. In animal models, calcineurin inhibitors have a positive growth effect, whereas target-of-rapamycin (TOR) inhibitors have a negative growth effect on malignant cells. METHODS: A multivariate analysis of posttransplant malignancies in 33,249 deceased donor primary solitary renal recipients reported by 264 kidney transplant programs to the Organ Procurement and Transplantation Network database from July 1, 1996 to December 31, 2001 was performed. Data were censored at 963 days to allow comparable follow-up time among drug treatment groups. The incidence and relative risks of any de novo malignancy (skin and solid) and for non-skin solid malignancies in patients receiving TOR inhibitors compared to patients receiving calcineurin inhibitors were the primary endpoints. RESULTS: The incidence rates of patients with any de novo posttransplant malignancy were 0.60% with sirolimus/everolimus alone, 0.60% with sirolimus/everolimus + cyclosporine/tacrolimus, and 1.81% with cyclosporine/tacrolimus (P<0.0001); the rates with a de novo solid tumor were 0%, 0.47%, and 1.00%, respectively. In the Cox regression model the relative risk associated with sirolimus/everolimus immunosuppression for any de novo cancer was 0.39 (95% CI: 0.24-0.64; P=0.0002) and for de novo solid cancer was 0.44 (0.24-0.82; P=0.0092). Other significant risk factors were male sex, adult age group, white race, and history of a malignancy. CONCLUSIONS: Maintenance immunosuppression with the TOR inhibitor drugs, sirolimus and everolimus, is associated with a significantly reduced risk of developing any posttransplant de novo malignancy and non-skin solid malignancy.

Everolimus↗

PubMed2006

Clinical utility of telomerase for the diagnosis of malignant well-differentiated endocrine tumours.

OBJECTIVE: The distinction between benign and malignant well-differentiated endocrine tumours is hard to achieve. The aim of the present study was to determine whether detection of telomerase or quantification of human telomerase reverse transcriptase protein subunit (hTERT) differ between benign and malignant endocrine tumours. PATIENTS AND METHODS: This retrospective study investigated 31 well-differentiated primary endocrine tumours. Based on clinical and histopathological criteria, tumours were categorized with the most recent WHO classification as 'benign' (n = 14), 'uncertain' (n = 5) or 'malignant' (n = 12) with (n = 7) or without (n = 5) metastasis after a mean follow-up of 40.4 +/- 25.8 months (4-122 months). All these tumours were assayed for telomerase activity and hTERT mRNA expression [real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR)]. RESULTS: Telomerase activity was detected in 7 malignant and metastatic tumours, in 1 malignant tumour without metastases, in 1 uncertain tumour and in 1 benign tumour. hTERT mRNA levels were significantly higher in malignant endocrine tumours with or without metastases (P = 0.001) when compared to benign tumours. The negative predictive value of hTERT mRNA quantification for the diagnosis of malignancy was 88.9%, whereas the positive predictive value was 68.7%. CONCLUSION: The presence of telomerase activity within the primary endocrine tumour might indicate a malignant tumour and might suggest the need for an attentive search for concomitant metastases. Quantification of hTERT mRNA could be used in clinical practice to exclude malignancy in most endocrine tumours.

Adrenal Gland Neoplasms↗

PubMed1997

Differential diagnosis of primary benign and malignant retroperitoneal tumors.

BACKGROUND: Clinical differential diagnosis between malignant and benign tumors is important in order to select a therapeutic strategy for a primary retroperitoneal tumor. METHODS: The clinical findings and radiological features of 25 patients with primary retroperitoneal tumors were retrospectively evaluated to find those signs that might contribute to the preoperative distinction between benign and malignant tumors. RESULTS: Of 25 primary retroperitoneal tumors, 15 were benign. This may reflect the increased number of incidentally found small benign tumors. There were significant associations between the presence of symptoms and malignancy (P < 0.05), between irregular margins on imaging and malignancy (P < 0.05) and between the absence of calcification and malignancy (P < 0.05). Malignant tumors were significantly larger than benign tumors (11.45 +/- 1.90 cm vs. 5.31 +/- 0.43 cm). A retroperitoneal tumor scoring system was developed to distinguish primary retroperitoneal benign tumors from their malignant counterparts based on the: 1) maximum diameter equal to or larger than 5.5 cm, 2) presence of symptoms, 3) absence of calcification, 4) presence of irregular margins, and 5) presence of cystic degeneration or necrosis. A significant correlation was found between the incidence of malignant tumors and the total retroperitoneal tumor score (P < 0.05). CONCLUSION: This study suggests that the size of tumor, the presence of symptoms, irregular margins, and the absence of calcification may be valuable predictors of primary retroperitoneal malignant tumor.

Adolescent↗