Reverse re-modelling chronic heart failure by reinstating heart rate variability.

Heart rate variability (HRV) is a crucial indicator of cardiovascular health. Low HRV is correlated with disease severity and mortality in heart failure. Heart rate increases and decreases with each breath in normal physiology termed respiratory sinus arrhythmia (RSA). RSA is highly evolutionarily conserved, most prominent in the young and athletic and is lost in cardiovascular disease. Despite this, current pacemakers either pace the heart in a metronomic fashion or sense activity in the sinus node. If RSA has been lost in cardiovascular disease current pacemakers cannot restore it. We hypothesized that restoration of RSA in heart failure would improve cardiac function. Restoration of RSA in heart failure was assessed in an ovine model of heart failure with reduced ejection fraction. Conscious 24 h recordings were made from three groups, RSA paced (n = 6), monotonically paced (n = 6) and heart failure time control (n = 5). Real-time blood pressure, cardiac output, heart rate and diaphragmatic EMG were recorded in all animals. Respiratory modulated pacing was generated by a proprietary device (Ceryx Medical) to pace the heart with real-time respiratory modulation. RSA pacing substantially increased cardiac output by 1.4 L/min (20%) compared to contemporary (monotonic) pacing. This increase in cardiac output led to a significant decrease in apnoeas associated with heart failure, reversed cardiomyocyte hypertrophy, and restored the T-tubule structure that is essential for force generation. Re-instating RSA in heart failure improves cardiac function through mechanisms of reverse re-modelling; the improvement observed is far greater than that seen with current contemporary therapies. These findings support the concept of re-instating RSA as a regime for patients who require a pacemaker.

Dataset for the reporting of urinary tract carcinoma-biopsy and transurethral resection specimen: recommendations from the International Collaboration on Cancer Reporting (ICCR).

The International Collaboration on Cancer Reporting (ICCR) is an alliance of major pathology organisations in Australasia, Canada, Europe, United Kingdom, and United States of America that develops internationally standardised, evidence-based datasets for the pathology reporting of cancer specimens. This dataset was developed by a multidisciplinary panel of international experts based on previously published ICCR guidelines for the production of cancer datasets. It is composed of Required (core) and Recommended (noncore) elements identified on the basis of literature review and expert consensus. The document also includes an explanatory commentary explaining the rationale behind the categorization of individual data items and provides guidance on how these should be collected and reported. The dataset includes nine required and six recommended elements for the reporting of cancers of the urinary tract in biopsy and transurethral resection (TUR) specimens. The required elements include specimen site, operative procedure, histological tumor type, subtype/variant of urothelial carcinoma, tumor grade, extent of invasion, status of muscularis propria, noninvasive carcinoma, and lymphovascular invasion (LVI). The recommended elements include clinical information, block identification key, extent of T1 disease, associated epithelial lesions, coexistent pathology, and ancillary studies. The dataset provides a structured template for globally harmonized collection of pathology data required for management of patients diagnosed with cancer of the urinary tract in biopsy and TUR specimens. It is expected that this will facilitate international collaboration, reduce duplication of effort in updating current national/institutional datasets, and be particularly useful for countries that have not developed their own datasets.

Direct Observation of Incoherent Cherenkov Diffraction Radiation in the Visible Range.

We report on the observation of incoherent Cherenkov radiation emitted by a 5.3 GeV positron beam circulating in the Cornell electron-positron storage ring as the beam passes in the close vicinity of the surface of a fused silica radiator (i.e., at a distance larger than 0.8 mm). The shape of the radiator was designed in order to send the Cherenkov photons towards the detector, consisting of a compact optical system equipped with an intensified camera. The optical system allows both the measurements of 2D images and angular distribution including polarization study. The corresponding light intensity has been measured as a function of the distance between the beam and the surface of the radiator and has shown a good agreement with theoretical predictions. For highly relativistic particles, a large amount of incoherent radiation is produced in a wide spectral range. A light yield of 0.8×10^{-3} photon per particle per turn has been measured at a wavelength of 600±10 nm in a 2 cm long radiator and for an impact parameter of 1 mm. This will find applications in accelerators as noninvasive beam diagnostics for both leptons and hadrons.

Dataset for the reporting of carcinoma of the bladder-cystectomy, cystoprostatectomy and diverticulectomy specimens: recommendations from the International Collaboration on Cancer Reporting (ICCR).

The International Collaboration on Cancer Reporting (ICCR) is a not for profit organisation whose goal is to produce standardised internationally agreed and evidence-based datasets for pathology reporting. With input from pathologists worldwide, the datasets are intended to be uniform and structured. They include all items necessary for an objective and accurate pathology report which enables clinicians to apply the best treatment for the patient. This dataset has had input from a multidisciplinary ICCR expert panel. The rationale for some items being required and others recommended is explained, based on the latest literature. The dataset incorporates data from the World Health Organization (WHO) 2016, and also from the latest (8th edition) TNM staging system of the American Joint Committee on Cancer (AJCC). Fifteen required elements and eight recommended items are described. This dataset provides all the details for a precise and valuable pathology report required for patient management and prognostication. This dataset is intended for worldwide use, and should facilitate the collection of standardised comparable data on bladder carcinoma at an international level.

Divergent differentiation in urothelial carcinoma and other bladder cancer subtypes with selected mimics.

Conventional urothelial carcinoma accounts for most carcinomas of the urinary tract lining. However, neoplastic urothelium has the capacity to demonstrate enormous plasticity. A variety of unusual architectural patterns of urothelial carcinoma, such as the nested, microcystic and inverted variants, can be mistaken for reactive processes or benign tumours. Others such as the micropapillary, plasmacytoid and discohesive variants, can mimic metastatic tumour from other sites. The micropapillary variant in particular is more aggressive. In addition, urothelial carcinoma has a propensity to demonstrate divergent differentiation with glandular, squamous, small cell neuroendocrine, lymphoepithelioma-like, sarcomatoid or other elements. Pure squamous carcinoma or adenocarcinoma (the latter in particular) can be difficult to distinguish from contiguous or metastatic spread. Some variants have prognostic and potential therapeutic implications. Molecular genetic evidence has emerged recently supporting a close relationship between urothelial carcinoma and various divergent elements. Sarcomatoid carcinoma and its differential diagnosis with other spindle cell lesions of urinary tract will be covered in a separate review.

The free energy for hydrolysis of a microtubule-bound nucleotide triphosphate is near zero: all of the free energy for hydrolysis is stored in the microtubule lattice.

The standard free energy for hydrolysis of the GTP analogue guanylyl-(a,b)-methylene-diphosphonate (GMPCPP), which is -5.18 kcal in solution, was found to be -3.79 kcal in tubulin dimers, and only -0.90 kcal in tubulin subunits in microtubules. The near-zero change in standard free energy for GMPCPP hydrolysis in the microtubule indicates that the majority of the free energy potentially available from this reaction is stored in the microtubule lattice; this energy is available to do work, as in chromosome movement. The equilibrium constants described here were obtained from video microscopy measurements of the kinetics of assembly and disassembly of GMPCPP-microtubules and GMPCP-microtubules. It was possible to study GMPCPP-microtubules since GMPCPP is not hydrolyzed during assembly. Microtubules containing GMPCP were obtained by assembly of high concentrations of tubulin-GMPCP subunits, as well as by treating tubulin-GMPCPP-microtubules in sodium (but not potassium) Pipes buffer with glycerol, which reduced the half-time for GMPCPP hydrolysis from > 10 h to approximately 10 min. The rate for tubulin-GMPCPP and tubulin-GMPCP subunit dissociation from microtubule ends were found to be about 0.65 and 128 s-1, respectively. The much faster rate for tubulin-GMPCP subunit dissociation provides direct evidence that microtubule dynamics can be regulated by nucleotide triphosphate hydrolysis.

Aqueductal CSF Stroke Volume Is Increased in Patients with Idiopathic Normal Pressure Hydrocephalus and Decreases after Shunt Surgery.

BACKGROUND AND PURPOSE: Increased CSF stroke volume through the cerebral aqueduct has been proposed as a possible indicator of positive surgical outcome in patients with idiopathic normal pressure hydrocephalus; however, consensus is lacking. In this prospective study, we aimed to compare CSF flow parameters in patients with idiopathic normal pressure hydrocephalus with those in healthy controls and change after shunt surgery and to investigate whether any parameter could predict surgical outcome. MATERIALS AND METHODS: Twenty-one patients with idiopathic normal pressure hydrocephalus and 21 age- and sex-matched healthy controls were prospectively included and examined clinically and with MR imaging of the brain. Eighteen patients were treated with shunt implantation and were re-examined clinically and with MR imaging the day before the operation and 3 months postoperatively. All MR imaging scans included a phase-contrast sequence. RESULTS: The median aqueductal CSF stroke volume was significantly larger in patients compared with healthy controls (103.5 µL; interquartile range, 69.8-142.8 µL) compared with 62.5 µL (interquartile range, 58.3-73.8 µL; P < .01) and was significantly reduced 3 months after shunt surgery from 94.8 µL (interquartile range, 81-241 µL) to 88 µL (interquartile range, 51.8-173.3 µL; P < .05). Net flow in the caudocranial direction (retrograde) was present in 11/21 patients and in 10/21 controls. Peak flow and net flow did not differ between patients and controls. There were no correlations between any CSF flow parameters and surgical outcomes. CONCLUSIONS: Aqueductal CSF stroke volume was increased in patients with idiopathic normal pressure hydrocephalus and decreased after shunt surgery, whereas retrograde aqueductal net flow did not seem to be specific for patients with idiopathic normal pressure hydrocephalus. On the basis of the results, the usefulness of CSF flow parameters to predict outcome after shunt surgery seem to be limited.

FTIR-based spectroscopic analysis in the identification of clinically aggressive prostate cancer.

Fourier transform infrared (FTIR) spectroscopy is a vibrational spectroscopic technique that uses infrared radiation to vibrate molecular bonds within the sample that absorbs it. As different samples contain different molecular bonds or different configurations of molecular bonds, FTIR allows us to obtain chemical information on molecules within the sample. Fourier transform infrared microspectroscopy in conjunction with a principal component-discriminant function analysis (PC-DFA) algorithm was applied to the grading of prostate cancer (CaP) tissue specimens. The PC-DFA algorithm is used alongside the established diagnostic measures of Gleason grading and the tumour/node/metastasis system. Principal component-discriminant function analysis improved the sensitivity and specificity of a three-band Gleason score criterion diagnosis previously reported by attaining an overall sensitivity of 92.3% and specificity of 99.4%. For the first time, we present the use of a two-band criterion showing an association of FTIR-based spectral characteristics with clinically aggressive behaviour in CaP manifest as local and/or distal spread. This paper shows the potential for the use of spectroscopic analysis for the evaluation of the biopotential of CaP in an accurate and reproducible manner.

Fibromatosis: benign by name but not necessarily by nature.

Aggressive fibromatoses, also known as desmoid tumours, are rare fibrous tissue proliferations with a tendency for slow, local infiltrative growth. There is an association with Gardner's syndrome and familial adenomatous polyposis. Histologically they are fairly bland with no abnormal mitoses or necrosis. They do not metastasize, but can cause significant morbidity through their locally destructive effects. Magnetic resonance imaging is the method of choice for diagnosis, pre-treatment planning and post-treatment follow-up. Surgical excision with a wide margin is the treatment of choice. However, there is a tendency for local recurrence and repeated excision may result in a poor functional or cosmetic outcome. Radiotherapy is used to reduce local recurrence rates after excision and is also used to treat inoperable tumours. Long-lasting remissions can be obtained. Treatment is now planned using modern three-dimensional conformal techniques, similar to those used in soft tissue sarcoma management. There is no definite dose-response relationship, but doses of 50-60 Gy in 1.8-2 Gy fractions are recommended. Systemic therapy has been used for lesions not controlled by surgery or radiotherapy, or less commonly, as a primary treatment. Tamoxifen and non-steroidal anti-inflammatory agents are used most often as they are relatively non-toxic, but there is limited experience with cytotoxic chemotherapy and biological agents. There are no randomised trials to help guide the management of this locally aggressive 'benign' tumour and treatment decisions are best made by the local soft tissue sarcoma multidisciplinary team.

The neoadjuvant approach in the treatment of patients with advanced epithelial ovarian carcinoma.

AIMS: Ovarian cancer has a very poor prognosis, with 5-year survival rates of 5-20% for advanced-stage disease. This work was designed to verify whether the neoadjuvant approach had an effect on survival in patients with advanced-stage ovarian cancer. MATERIALS AND METHODS: Patients with stage III or IV disease who received neoadjuvant platinum-based chemotherapy (group 1) were compared with a group of conventionally treated patients (group 2). RESULTS: Most of the patients in group 1 (76%) had partial tumoral responses after chemotherapy. Patients from group 1 (n = 42) had a median survival that was not different from that in patients from group 2 (n = 348). Patients who received platinum-based chemotherapy with taxanes had the same survival of patients who received no taxanes. CONCLUSIONS: Our results showed similar responses and survival rates for patients with stage III or IV ovarian cancer treated with neoadjuvant platinum-based chemotherapy, when compared with patients who underwent primary suboptimal cytoreductive surgery. Our data therefore support the ongoing trials to determine the optimum timing of surgery for ovarian cancer.

Evidence that a single monolayer tubulin-GTP cap is both necessary and sufficient to stabilize microtubules.

Evidence that 13 or 14 contiguous tubulin-GTP subunits are sufficient to cap and stabilize a microtubule end and that loss of only one of these subunits results in the transition to rapid disassembly(catastrophe) was obtained using the slowly hydrolyzable GTP analogue guanylyl-(a,b)-methylene-diphosphonate (GMPCPP). The minus end of microtubules assembled with GTP was transiently stabilized against dilution-induced disassembly by reaction with tubulin-GMPCPP subunits for a time sufficient to cap the end with an average 40 subunits. The minimum size of a tubulin-GMPCPP cap sufficient to prevent disassembly was estimated from an observed 25- to 2000-s lifetime of the GMPCPP-stabilized microtubules following dilution with buffer and from the time required for loss of a single tubulin-GMPCPP subunit from the microtubule end (found to be 15 s). Rather than assuming that the 25- to 2000-s dispersion in cap lifetime results from an unlikely 80-fold range in the number of tubulin-GMPCpP subunits added in the 25-s incubation, it is proposed that this results because the minimum stable cap contains 13 to 14 tubulin-GMPCPP subunits. As a consequence, a microtubule capped with 13-14 tubulin-GMPCPP subunits switches to disassembly after only one dissociation event (in about 15 s), whereas the time required for catastrophe of a microtubule with only six times as many subunits (84 subunits) corresponds to 71 dissociation events (84-13). The minimum size of a tubulin-GMPCPP cap sufficient to prevent disassembly was also estimated with microtubules in which a GMPCPP-cap was formed by allowing chance to result in the accumulation of multiple contiguous tubulin-GMPCPP subunits at the end, during the disassembly of microtubules containing both GDP and GMPCPP. Our observation that the disassembly rate was inhibited in proportion to the 13-14th power of the fraction of subunits containing GMPCPP again suggests that a minimum cap contains 13-14 tubulin-GMPCPP subunits. A remeasurement of the rate constant for dissociation of a tubulin-GMPCPP subunit from the plus-end of GMPCPP microtubules, now found to be 0.118 s-1, has allowed a better estimate of the standard free energy for hydrolysis of GMPCPP in a microtubule and release of Pi: this is +0.7 kcal/mol, rather than -0.9 kcal/mol, as previously reported.

The interval from surgery to chemotherapy in the treatment of advanced epithelial ovarian carcinoma.

BACKGROUND: To study the effect of the interval between surgery and the start of chemotherapy in the treatment of patients with advanced ovarian cancer. METHODS: We stratified patients according to the start of platinum-based chemotherapy in group 1 (within 4 weeks from surgery), group 2 (between 4 and 8 weeks) and group 3 (between 8 and 12 weeks). RESULTS: Three hundred and ninty-four stage III ovarian cancer patients were analysed. In the multivariate analysis there were no differences in survival according to the interval between surgery and chemotherapy among the three groups. The independent prognostic variables were type of procedure (p = 0.014), performance status (p = 0.040) and post-chemotherapy CA-125 (p < 0.0001). CONCLUSIONS: The interval between surgery and chemotherapy does not affect outcome.

High-dose interleukin2 - a 10-year single-site experience in the treatment of metastatic renal cell carcinoma: careful selection of patients gives an excellent outcome.

BACKGROUND: VEGF-targeted therapy has become the mainstay of treatment for majority of mRCC patients. For most patients, benefit is short-lived and therefore treatment remains palliative in intent. HD IL2 is an effective immunotherapy treatment capable of durable remission in some patients but its unselected use has been difficult due to its modest response rate and considerable adverse effects. Using set pathology criteria as a selection tool in clinical practice, we have been able to show improved outcomes in our previous report. Here, we present an updated and extended report of this treatment and seek to explore any pathological, clinical and treatment variables likely to predict better outcomes. METHODS: This is an extension of a previously reported clinical audit, which includes mRCC cases treated with HD IL2 between 2003 and 2013. Since 2006, tumour specimens of potential candidates were routinely reviewed prospectively and stratified into Favourable or Other categories based on constitution of histological growth pattern, namely alveolar or solid versus papillary and/or sarcomatoid architecture; clear cell versus granular cell cytoplasmic morphology. HD IL2 was preferentially offered to patients with Favourable pathology. Outcome evaluation includes response rates, survival, and treatment tolerance. Multivariate analysis was performed to explore potential prognostic and predictive factors. RESULTS: Among prospectively selected patients with Favourable pathology (n = 106), overall response rate was 48.1 % (51/106) with CR rate of 21.6 % (23/106). Median OS was 58.1 months. Factors associated with significantly better response and/or survival includes favourable pathology pattern, higher cycle 1 tolerance and lower number of metastatic organ sites (<3). CAIX (Carbonic anhydrase 9) has prognostic value but is not predictive of response. Toxicities were those expected of IL2 but were manageable on general medical wards, with no treatment-related death. Importantly most complete responses were durable with 76 % (23/30) cases remained relapse-free (median 39 months follow up) and 2 of the seven who relapsed had had long-term disease free survival after resection of oligometastatic relapse. CONCLUSIONS: Our experience shows that HD IL2 remains an effective and safe treatment in well-selected cases of mRCC. The result in this single-institution patient series confirms similar outcomes to our previously reported retrospective series. Given the prospect of long-term remission, fit patients with Favourable histology and low disease burden should be considered for HD IL2 in an experienced centre. Better understanding has been gained from this in-depth analysis especially the examination of possible response predictors and strategies that can improve treatment outcome.

Plant 'hairy root' culture.

Due to their fast growth rates and biochemical stability, 'hairy root' cultures remain unsurpassed as the choice for model root systems and have promise as a bioprocessing system. Applications are wide-ranging, from the production of natural products and foreign proteins to a model for phytoremediation of organic and metal contaminants. Hairy roots will have a continuing role as an experimental model in plant metabolic engineering.

Regressed cutaneous malignant melanoma mimicking lymphoma: a potential diagnostic pitfall.

We report 2 cases of partially regressed malignant melanoma in which the brisk lymphocytic response closely resembled mycosis fungoides in 1 case and nodular sclerosing Hodgkin lymphoma in the other. Striking epidermotropism was present in both cases. The lymphocytes were predominantly of T8 cytotoxic subtype, and oligoclonal T-cell expansion was detected in 1 of the cases. The scanty residual melanoma cells were highlighted with HMB45 and S100 protein. We highlight the features of regression in melanoma that may lead to an erroneous diagnosis of lymphoma and discuss the finding of oligoclonal T-cell expansion in regressed melanocytic lesions.

Foci of amorphous/granulofilamentous matrix in the extracellular domain of tumours. 2. Immunohistochemical and immunogold characterization of a fibronectin-rich matrix component.

The term FEAM (foci of extracellular amorphous matrix) has been used for discretely outlined areas of moderately dense material having a filamentous/granular substructure located in the extracellular matrix of tumours. In spite of being widespread in mesenchymal tumours especially, and often abundant, they have received little attention in terms of structure, composition and origin. Mostly, they have been regarded as a variant or a product of lamina ('basement membrane material'). However, they also appear in tumours whose cells should and do lack a lamina, such as giant-cell fibroblastoma and solitary fibrous tumour. This paper describes their fine structure in a variety of predominantly mesenchymal tumours, and documents their composition using light microscope immunostaining and immunogold labelling. Small amounts of type IV collagen and laminin were found focally and inconsistently among the five tumours by light microscope immunostaining, but fibronectin was strongly and consistently identified. Strong fibronectin staining was also identified by immuno-electronmicroscopy. These data suggest that FEAM represent a fibronectin-rich matrix constituent, which might be a common final product of either lamina or the external component of the subplasmalemmal linear density (focal adhesion). There is little support light microscopically for a relationship to immune-complexes or cryoglobulins.

p53 and related proteins in epithelial ovarian cancer.

We conducted a retrospective immunohistochemical evaluation of the prognostic significance of the expression of p53 and the related proteins Bax, Bcl-2, growth arrest and DNA damage (Gadd45), murine double minute 2 (Mdm2) and p21(WAF1/CIP1) in chemonaive tumours taken from 66 patients with ovarian cancer. Ki-67 expression (a marker of cell proliferation) was also evaluated immunohistochemically, while apoptosis within malignant cells was determined with the terminal deoxynucleotidyltransferase-mediated dUTP nick-end labelling (TUNEL) assay. The expression of each of the following proteins was significantly associated in the tumours (P < 0.05 unless otherwise stated): Bax with Bcl-2 (P < 0.01); Bax with Mdm2; p21(WAF1/CIP1) with Gadd45 (P < 0.01); p21(WAF1/CIP1) with p53; p53 with Mdm2. Univariate analysis showed that expression of p53, Bax, bulk residual disease and International Federation of Gynecology and Obstetricians (FIGO) stage were all strongly correlated with response to chemotherapy (P < 0.01). Similarly, the FIGO stage and Ki-67 expression (P < 0.01), as well as pathological subtype and bulk residual disease (P < 0.05), were prognostic factors for disease progression. The FIGO stage and Ki-67 expression were significant prognostic factors for overall survival (P < 0.01), with Gadd45 expression and pathological subtype also significant (P < 0.05) in a univariate analysis. Multivariate analysis for response to chemotherapy showed that expression of p53, Bax and FIGO stage were all independent prognostic factors (P < 0.01). The FIGO stage was the most important independent prognostic factor for progression and survival on multivariate analysis (P < 0.01). However, Ki-67 expression was also an independent prognostic factor for disease progression (P < 0.05) and approached significance for survival (P = 0.055). Taken together, these data suggest that determination of Ki-67 expression could supplement established prognostic factors.

Immunohistochemical study of testicular sex cord-stromal tumors, including staining with anti-inhibin antibody.

Inhibin is a peptide hormone produced by ovarian granulosa cells and testicular Sertoli cells. Ovarian granulosa cell and other sex cord-stromal tumors usually exhibit positive immunohistochemical staining with antiinhibin antibodies, and this may be valuable in differentiating these neoplasms from histologic mimics. In the present study, we investigated the immunohistochemical staining of testicular sex cord-stromal tumors using antiinhibin. Immunostaining with CAM5.2, vimentin, S-100 protein, desmin, epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), and placental alkaline phosphatase (PLAP) also was performed because few studies have investigated in detail the immunophenotype of testicular sex cord-stromal tumors. Fifteen of 16 Leydig cell tumors exhibited strong positive staining with antiinhibin. A proportion of Leydig cell tumors also stained positively with CAM5.2 (7 of 16), vimentin (14 of 16), S-100 protein (10 of 16), desmin (2 of 16) and epithelial membrane antigen (4 of 16). Four of six testicular sex cord-stromal tumors with varying degrees of Sertoli or granulosa cell differentiation were positive with antiinhibin, as were two of three sex cord-stromal tumors that were unclassified. Some of these tumors were positive with CAM 5.2, vimentin, S-100 protein, desmin, and epithelial membrane antigen. All tumors were negative with carcinoembryonic antigen and placental alkaline phosphatase. The immunohistochemical findings show that, analogous to their ovarian counterparts, most testicular sex cord-stromal tumors are immunoreactive with antiinhibin. Immunohistochemistry using this antibody as part of a panel may be valuable in confirming a diagnosis of testicular sex cord-stromal tumor and in differentiating these neoplasms from others that may mimic them.

Mesotheliomas with deciduoid morphology: a morphologic spectrum and a variant not confined to young females.

Deciduoid mesotheliomas are rare with only four previously reported cases, all affecting the peritoneum of young females. We describe another six cases (three men and three women; age range 52-65 yrs, median 55 yrs; five peritoneal and one pleural). Three patients had an occupational history of asbestos exposure. The deciduoid appearance predominated in four cases, whereas in two it represented a minor component within conventional tubulopapillary epithelioid mesothelioma. All tumors were strongly cytokeratin-positive (including CK5/6) and all showed at least focal staining for thrombomodulin, HBME-1, and calretinin. All were negative for epithelial mucin (D/PAS), CEA, BerEP4, LeuM1 (CD15), CD21, CD35, and S100 protein. Five of six cases (83%) were vimentin-positive and two (33%) were focally positive for alpha-smooth muscle actin. A differential diagnosis of gastrointestinal autonomic nerve tumor (GANT) had been initially considered from the morphology of one case, and we found positivity for some of the "neuronal" markers described in GANTs. This prompted us to apply such a panel to the other five tumors, accepting that the cytokeratin positivity encountered in all of our cases would exclude GANT. All cases of deciduoid mesothelioma (100%) were positive for PGP 9.5 and NSE and four of six (66%) were positive for NKI/C3. Weak focal staining (<5% cells) for synaptophysin was seen in two of six tumors. All cases were chromogranin-negative. All cases examined by electron microscopy showed desmosomes and smooth microvilli without rootlets but no neuroendocrine granules. In conclusion, a deciduoid morphology appears to be part of the histopathologic spectrum encountered in epithelioid mesothelioma. This variant is not confined to female patients and occurs over a wider age range than previously recognized. The overlapping immunophenotype with GANTs illustrates that caution should be exercised when interpreting positivity for "neuronal" markers in this context. An immunohistochemical panel that includes cytokeratins should always be used.