Pure Uterine Lipoma with a Combined Mucinous Cystic and Brenner Ovarian Tumor in a Postmenopausal Woman: A Case Report and Review of the Literature.

Lipomatous tumors are rare among uterine mesenchymal tumors. Due to their rarity, information on the clinical development and histological origin are lacking. We report a pure uterine lipoma and present a review of the relevant literature. We encountered a 72-year-old postmenopausal woman who was referred to our hospital. Computed tomography (CT) and magnetic resonance imaging (MRI) examinations revealed degenerative uterine tumors and a left ovarian cystic tumor with a solid portion. Total hysterectomy and bilateral salpingo-oophorectomy were performed, and postoperative histological examination revealed a uterine lipoma and adenomyosis. The cystic portion was a mucinous cystadenoma, and the solid portion was classified as a Brenner tumor. The postoperative course was uneventful, and the patient was discharged and remained well until follow-up. Our observations suggest that imaging examinations are sufficient for the diagnosis of uterine lipomatous tumors. To the best of our knowledge, the coexistence of a pure uterine lipoma and a mucinous Brenner ovarian tumor has not been documented in the existing literature. The histogenesis of uterine lipomas remains unclear. However, our results, and those from the existing literature, indicate that the mesenchymal stem cells surrounding the perivascular tissue may be implicated, because lipomas of the skin are reported to originate from these cells.

Evaluation of Postmortem Drug Concentrations in Bile Compared with Blood and Urine in Forensic Autopsy Cases.

For drug screening and pharmaco-/toxicokinetic analysis, bile as a major drug excretion route in addition to urine may be used in forensic autopsy cases; however, there are limited published data on correlations between bile and blood or urine drug concentrations. The present study retrospectively investigated drug concentrations in bile, compared with blood and urine concentrations, reviewing forensic autopsy cases during 6 years (January 2009-December 2014). Drugs were analyzed using automated gas chromatography-mass spectrometry following solid-liquid phase extraction. Compared with peripheral blood concentrations, bile concentrations were higher for most drugs; however, caffeine concentrations were similar. Bile concentrations were mostly lower than urine concentrations for amphetamines, caffeine and methylephedrine, but were usually similar to or higher for other drugs. Significant correlations were detected between bile and peripheral blood concentrations for amphetamines, several cold remedies, phenobarbital, phenothiazine derivatives and diazepam, as well as between bile and urine concentrations for amphetamines, caffeine, diphenhydramine, phenobarbital and promethazine derivatives. These findings suggest that bile can provide supplemental data useful in routine forensic toxicology, for the spectrum of drugs mentioned above, as well as for investigating pharmaco-/toxicokinetics and postmortem redistribution when analyzed in combination with drug concentrations at other sites.

Evaluation of the on-site immunoassay drug-screening device Triage-TOX in routine forensic autopsy.

Instrumental identification of drugs with quantification is essential in forensic toxicology, while on-site immunoassay urinalysis drug-screening devices conveniently provide preliminary information when adequately used. However, suitable or sufficient urine specimens are not always available. The present study evaluated the efficacy of a new on-site immunoassay drug-screening device Triage-TOX (Alere Inc., San Diego, CA, USA), which has recently been developed to provide objective data on the one-step automated processor, using 51 urine and 19 pericardial fluid samples from 66 forensic autopsy cases, compared with Triage-Drug of Abuse (DOA) and Monitect-9. For benzodiazepines, the positive predictive value and specificity of Triage-TOX were higher than those of Triage-DOA; however, sensitivity was higher with Monitect-9, despite frequent false-positives. The results for the other drugs with the three devices also included a few false-negatives and false-positives. These observations indicate the applicability of Triage-TOX in preliminary drug screening using urine or alternative materials in routine forensic autopsy, when a possible false-negative is considered, especially for benzodiazepines, providing objective information; however, the combined use of another device such as Monitect-9 can help minimize misinterpretation prior to instrumental analysis.

Evaluation of postmortem drug concentrations in cerebrospinal fluid compared with blood and pericardial fluid.

In forensic toxicology, body fluids are important materials not only as alternatives to blood but also for investigation of postmortem drug redistributions and pharmaco-/toxicokinetic analysis; however, there are limited data on postmortem drug distributions in cerebrospinal fluid (CSF). The present study reviewed toxicological data of autopsy cases (n=103), in which drugs were detected in CSF using gas chromatography/mass spectrometry (GC/MS), to investigate drug concentrations in CSF, compared with blood and pericardial fluid (PCF) concentrations. Oral/injected amphetamines (n=23) showed similar CSF and blood/PCF concentrations with partly lower CSF concentrations (about ×0.5-1.1). CSF concentrations of the venous anesthetic midazolam (n=7) were lower with poor correlations. Oral caffeine (n=15), acetaminophen (n=7), chlorpheniramine (n=6), dihydrocodeine (n=6), and phenobarbital (n=21) showed equivalent to lower CSF concentrations (about ×0.2-1.2), compared with blood and PCF concentrations; however, CSF phenobarbital concentrations were high in a fatal intoxication case. CSF concentrations of phenothiazine derivatives (n=29) were markedly lower (about ×0.1) than blood/PCF concentrations. The distribution of the local anesthetic lidocaine used in critical medical care (n=49) markedly varied by case. These findings suggest that CSF is useful in routine forensic toxicology as an alternative to blood as well as for investigating pharmaco-/toxicokinetics and postmortem redistributions.

Efficacy of drug screening in forensic autopsy: retrospective investigation of routine toxicological findings.

Toxicological analysis is indispensable in forensic autopsy laboratories, but often depends on the limitations of individual institutions. The present study reviewed routine drug screening data of forensic autopsy cases (n=2996) during an 18.5-year period (January 1996-June 2014) at our institute to examine the efficacy of the procedures and findings in autopsy diagnosis and interpretation. Drug screening was performed using on-site immunoassay screening devices and gas chromatography/mass spectrometry (GC/MS) in all cases, followed by re-examination using GC/MS and liquid chromatography/tandem mass spectrometry (LC/MS/MS) at a cooperating institute in specific cases in the last 4 years. GC/MS detected drugs in 486 cases (16.2%), including amphetamines (n=160), major tranquilizers (n=72), minor tranquilizers (n=294), antidepressants (n=21), cold remedies (n=77), and other drugs (n=19). Among these cases, fatal intoxication (n=123) involved amphetamines (n=73), major tranquilizers (n=37), minor tranquilizers (n=86), antidepressants (n=3), and cold remedies (n=9); most cases involved self-administration, alleged suicide and accidental overdose, while homicide was not included. These drugs were also identified in other manners of death, including homicide (n=40/372), suicide (n=34/226), accidental falls (n=27/129), and natural death (n=72/514). In these cases, on-site immunoassay screening of drugs of abuse showed negative findings in 2440 cases (81.4% in all cases), while GC/MS detected other drugs in 218 cases (7.3% in all cases), including several antipsychotic drugs, acetaminophen and salicylic acid. Further analysis using LC/MS/MS detected low concentrations of benzodiazepines in 32 cases, and also anti-diabetic and hypertensive drugs in a case of fatal abuse. These observations indicate the efficacy of systematic routine toxicological analysis to investigate not only the cause of death but also the background of fatalities in forensic autopsy. The provision of extensive drug screening is needed for forensic and social risk management, considering the marked diversity of medical and illicit drugs.

Postmortem analyses of drugs in pericardial fluid and bone marrow aspirate.

In forensic toxicology, bone marrow is often used when adequate blood samples are not available; however, pericardial fluid (PCF) has been poorly investigated. The present study comprehensively reviewed the toxicological data of blood, PCF and bone marrow aspirate (BMA) in forensic autopsy cases to investigate drug distribution. Analysis using automated gas chromatography/mass spectrometry (GC-MS) following solid/liquid phase extraction detected 36 drugs in 218 cases (8.0% among 2,724 cases examined). Drug distribution varied by drug as well as partly by case even when taken as a mixture. Most of the drugs showed overall similar distributions in right heart blood, PCF and BMA with some exceptions, however, several drugs, including phenothiazine derivatives and antidepressants, were detected at ∼1.5 times (1.2-2.0) higher levels in BMA than in right heart blood, but PCF levels were mostly equivalent to blood levels. Midazolam, propofol and thiamylal (intravenous anesthetics) were detected at a substantially lower concentration in PCF than in blood or BMA. These observations suggest that PCF and BMA are useful materials to be included in the forensic toxicological routine when blood samples are not available, as well as to investigate pharmaco-/toxicokinetics and postmortem redistribution.

Postmortem analyses of gaseous and volatile substances in pericardial fluid and bone marrow aspirate.

A previous study suggested the usefulness of pericardial fluid (PCF) and bone marrow aspirate (BMA) for the postmortem analysis of ethanol. The present study reviewed forensic autopsy cases (n = 2,983), which included 683 cases with the following positive toxicological findings, to reassess ethanol distribution and to investigate other gaseous and volatile substances in blood, PCF and BMA. Toxicological analyses detected ethanol (>10 mg/dL, n = 345), acetone (>0.01 mg/dL, n = 402), cyanide (n = 282), toluene (n = 47), liquefied petroleum gas (LPG, n = 1), cresol (n = 1), trichloroethylene (TCE, n = 1) and hydrogen sulfide (H2S, n = 5) in 683 cases. Ethanol and acetone levels showed good correlations among right heart/peripheral blood, PCF and BMA with a few exceptions. Inhaled cyanide in a fire fatality and H2S in suicidal inhalation were substantially lower in PCF than in blood and BMA; however, ingested cyanide showed a higher level in PCF. Distribution of inhaled toluene largely varied by case; however, BMA levels were about twice as high as blood levels in abusers (n = 7). Inhaled LPG and TCE were also higher in BMA than in blood, whereas ingested cresol showed similar distributions in blood and PCF. These observations suggest the usefulness of PCF and BMA as alternatives to blood for postmortem toxicological analysis. The inclusion of these materials in routine analysis may be also useful to investigate pharmacokinetics and toxicokinetics in the death process and the influence of postmortem redistribution/diffusion.