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Acute myeloid leukaemia (AML) is a rare haematologic cancer with a rapid increase in blast cells, which need to be rapidly diagnosed and treated. The aim of this report is to analyse the rare phenomenon of AML diagnosed at autopsy after sudden death. We report three cases of AML and perform a literature review using the mesh terms "sudden death" and "leukaemia". We report the cases of three young women diagnosed with AML only after autopsy. We found seven articles which reported sudden death due to AML diagnosed at autopsy. Diagnosis of AML during autopsy is rare but can raise forensic issues. A complete autopsy with pathology analysis is needed.

OBJECTIVES Proteomic analysis of vestibular schwannoma (VS), non-vestibular schwannoma (NVS), and normal nerve (NN) using mass spectrometry and imaging of matrix assisted laser desorption ionization-time of flight (MALDI-TOF). METHODS Retrospective, qualitative, and descriptive study on VS, NVS, and NN. Samples were provided by our Tumor Bank. They were analyzed histologically then sprayed by acid matrix. The laser beam of MALDI performed desorption-ionization of the sample. A mass spectrogram (MS) was drawn depending on time of flight of ionized peptides, and MALDI-imaging was obtained which is a summation color spectrum depending on sample's peptide content. The slice was reexamined histologically and results compared with MALDI-imaging. RESULTS Fifty schwannomas were sampled, of which 27 exploitable: 22 VS (17 Antoni type A and five type B) and five NVS (all Antoni type B). Eleven NN were analyzed. Among the 22 VS, near-total correlation between MALDI-imaging and pathology was found in two cases (9.1%), partial correlation in four (18.2%), and no correlation in 16 (72.7%); correlations were more frequent in VS of the Antoni type B. MS showed a peptide spike at 2,000 m/z in 7 (31.8%) and 5,000 m/z in 21 (95.5%). Among the five NVS, near-total correlation was found in three cases (60%), partial correlation in one (20%), and no correlation in one (20%). MS showed a peptide spike at 2,000 m/z in two (40%) and 5,000 m/z in all (100%). Among the 11 NN, near-total correlation was found in nine cases (81.8%), partial correlation in one (9.1%), and no correlation in one (9.1%). MS showed no peptide spike at 2,000 or 5,000 m/z. Behind homogeneous areas on histology, there was great heterogeneity on MALDI-imaging and MS, regarding VS and NVS, but not NN. CONCLUSIONS There was a lack of correlation between MALDI-imaging and pathology in VS (except Antoni type B) as compared with NVS and NN. The lack of correlation in VS of the type A as compared with type B VS and NVS could be attributed to the overexpression of degeneration-associated proteins/peptides in VS of the type B as well as NVS that are better correlated with histologic findings. The two peptide spikes detected in schwannoma and not in NN opens up the prospect of tumor biomarkers identifiable by sequencing. The proteomic polymorphism found in VS and NVS was absent on histology which is a new morphologic characteristic of schwannoma. Further studies should be performed in the future to confirm the benefit and usefulness of the MALDI in the analysis of VS and NVS.

PD-L1 immunohistochemical expression is used as an important theranostic marker in various malignancies, including head and neck squamous cell carcinoma (HNSCC) where the combined positive score (CPS) guides treatment decisions. Despite indirect evidence that there is loss of antigenicity for archived tissues, there is no direct comparison between PD-L1 expression of the same tissue upon arrival and after its storage.We compared the immunohistochemical expression of PD-L1 (22C3) in 106 HNSCC upon their arrival and after their storage (interval ranging from 20 to 48 months, mean 30.8 months). The evaluation was performed by two different pathologists' groups.We found a statistically significant decrease in the PD-L1 tumor proportional score (TPS), immune cells expression (IC) and CPS between the initial and the newly stained slides.This is the first study comparing PD-L1 expression between a tissue and "himself" later in time, highlighting an important decrease in expression by tumor and immune cells, and suggesting that an immediate rather than a retrospective assay of PD-L1 expression should be preferable in the routine practice.Data are available upon reasonable request.

Despite autophagy being a principal mechanism of tumor progression, its role has been never studied in Paget disease, a difficult to treat intraepithelial neoplasia affecting mainly the breast and the vulvar regions.Twenty seven cases (17 extramammary and 10 mammary) of Paget disease were immunohistochemically studied for the expression of the two principal autophagic factors, LC3B and p62.The majority of Paget diseases showed strong cytoplasmic expression of p62 in contrast to nearby keratinocytes which presented nuclear-only p62 staining. LC3B was negative or only mildly positive in neoplastic cells. No difference was seen between mammary and extramammary cases.The immunohistochemical autophagic profile of Paget disease suggests a down-regulated autophagic process which, thus, may be implicated in the invasive potential of these cells.

Pleural effusions are a common respiratory condition with many etiologies. Nonmalignant etiologies explain most pleural effusions and despite being nonmalignant, they can be associated with poor survival; thus, it is important to understand their pathophysiology. Furthermore, diagnosing a benign pleural pathology always harbors the uncertainty of a false-negative diagnosis for physicians and pathologists, especially for the group of non-specific pleuritis. This review aims to present the role of the inflammation in the development of benign pleural effusions, with a special interest in their pathophysiology and their association with malignancy.

It has been suggested that a primary tumor can “prepare” the draining of lymph nodes to “better accommodate” future metastatic cells, thus implying the presence of a premetastatic lymph node niche. However, this phenomenon remains unclear in gynecological cancers. The aim of this study was to evaluate lymph-node draining in gynecological cancers for premetastatic niche factors, such as myeloid-derived suppressor cells (MDSCs), immunosuppressive macrophages, cytotoxic T cells, immuno-modulatory molecules, and factors of the extracellular matrix. This is a monocentric retrospective study of patients who underwent lymph-node excision during their gynecological-cancer treatment. In all, 63 non-metastatic pelvic or inguinal lymph nodes, 25 non-metastatic para-aortic lymph nodes, 13 metastatic lymph nodes, and 21 non-cancer-associated lymph nodes (normal controls) were compared for the immunohistochemical presence of CD8 cytotoxic T cells, CD163 M2 macrophages, S100A8/A9 MDSCs, PD-L1+ immune cells, and tenascin-C, which is a matrix remodeling factor. PD-L1-positive immune cells were significantly higher in the control group, in comparison to the regional and distant cancer-draining lymph nodes. Tenascin-C was higher in metastatic lymph nodes than in both non-metastatic nodes and control lymph nodes. Vulvar cancer-draining lymph nodes showed higher PD-L1 values than endometrial cancer and cervical cancer-draining lymph nodes. Endometrial cancer-draining nodes had higher CD163 values and lower CD8 values, compared to vulvar cancer-draining nodes. Regarding regional draining nodes in low- and high-grade endometrial tumors, the former showed lower S100A8/A9 and CD163 values. Gynecological cancer-draining lymph nodes are generally immunocompetent, but vulvar cancer draining nodes, as well as high-grade endometrial cancer draining nodes, are more susceptible to harboring premetastatic niche factors.

Meningioma is the most frequent meningeal neoplasm, usually without relapse or metastasis. Patient follow-up is challenging, not standardized and is decided in multidisciplinary case discussion. Our aim was to determine the clinical and histological factors influencing the time to relapse.We conducted a single-Center retrospective study on 38 patients with surgically-excised relapsing meningiomas and collected clinical and pathological data.Our results show that none of the histological factors included in the WHO classification, nor those not included are related to a shorter time to relapse.In our study, none of the histological, immunohistochemical and clinical parameters evaluated seem to be able to predict the time to relapse in meningioma.

The term chordoid glioma of the third ventricle was first used to describe a rare and slowly growing neoplasm of uncertain histogenesis, with chordoid appearance, occurring preferentially in middle-aged women. Herein we report two additional examples of this novel entity together with a literature review based on the 25 cases previously published. Our review fully confirms the strikingly stereotyped clinical, neuroradiologic, and pathologic features of this unique tumor. The female/male ratio was 1.7:1, and the age range was 24-70 years (mean 44.9 years). In all 27 cases imaging findings were similar showing a well-defined mass (mean 2.8 cm in largest dimension), ovoid in shape, hyperdense on CT scans, with uniform and intense contrast enhancement, arising in the hypothalamic/suprasellar/third ventricular region. Histologically, the main consistent characteristics were cords and clusters of epithelioid cells within an abundant mucinous and often vacuolated background. Mitoses were sparse or absent and anaplastic features, endothelial proliferation, and necrosis were not identified. Lymphoplasmacytic infiltrates with Russell bodies were frequent throughout the tumor and its interface with adjacent brain parenchyma. Most of the tumor cells revealed a strong and diffuse expression of vimentin and glial fibrillary acidic protein. Additionally, the vast majority of tumors showed focal coexpression of cytokeratins, CD34, S-100 protein, and epithelial membrane antigen; the MIB-1 labeling indices were uniformly low. Surprisingly for a glioma assigned WHO grade II, the 19 patients with an available but short follow-up (mean 22.5 months; range 6-68 months) experienced a rather poor outcome (three recurrences and seven deaths), probably reflecting the anatomic site of the neoplasm that precludes a complete surgical excision rather than its histologic composition. Ultrastructural examination of 10 cases demonstrated findings in line with a glial derivation and a putative ependymal origin such as cytoplasmic intermediate filaments, microvilli, intermediate junctions or desmosomes, and focal basal lamina formation. In our case no. 1, and for the first time in this tumor, we observed sparse and abnormal cilia in an aberrant juxtanuclear location, a further argument for considering chordoid glioma as a subtype of ependymoma. However, a better understanding of the biologic behavior and histogenesis of this distinctive clinicopathologic entity needs to be investigated with a larger series. Nevertheless, taking into account its strikingly consistent anatomic localization, its unique histopathologic and immunohistochemical profile, in conjunction with the most recent and convincing ultrastructural arguments, we suggest that chordoid glioma of the third ventricle could be better classified as chordoid ependymoma of the lamina terminalis area.

To report on a series of fine needle aspiration (FNA) biopsies for preoperative diagnosis of complex cystic renal mass.From August 2002 to February 2009, 32 patients with a complex cystic renal mass were studied. Tumor size ranged from 1.5-7.7 cm, with a median of 3.0 cm. Bosniak classification was 15 IIF, 12 III, and 5 IV. FNA biopsy was performed under CT guidance to obtain the fluid. Malignant and suspect cytological reports were considered as a positive diagnosis, and absence of epithelial cells as a negative diagnosis.Sufficient fluid was obtained in all cases. A positive preoperative diagnosis was found in 11 patients, and 21 cysts presented as absence of epithelial cells. Of the 26 patients who underwent surgery, pathology proved that there were 21 malignant and 5 benign cysts. Among the operated patients with a malignant cystic tumor, 11/21 (52.3%) presented a negative preoperative diagnosis. One preoperative positive diagnosis was proved to be a benign cyst. The accuracy of preoperative positive cytology was 10/11 (90.9%).No difficulty was noticed in obtaining the fluid by FNA of a cystic small renal mass. A false negative diagnosis was due mainly to the absence of malignant cells in the fluid of cysts. Biomarkers in fluid shall be studied to solve the diagnostic problem.

Twenty years ago, theoretical developments were initiated to model the behavior of the NMR transverse relaxation rates in presence of vessels. These developments enabled the MRI-based mapping of mean vessel diameter, microvascular density, and vessel size index with comparable results to those obtained by a pathologist. The transfer of these techniques to routine clinical use has been hindered by the unavailability of the required sequences, namely fast gradient-echo spin-echo sequences. Based on the increasing accessibility of such sequences on MRI scanners over recent years, we review the principles governing microvascular MRI, the validation studies, and the applications that have been tested worldwide by several teams. We also provide some recommendations on how to measure microvessel caliber and density with MRI.

There is limited research on cell-free RNA (cf-RNA) in the urine of cancer patients. The present study was performed to detect the cf-RNA in the urine of patients with clear cell renal cell carcinoma (ccRCC). Ninety-five urine samples from ccRCC patients and 50 urine samples from control subjects were analyzed. The cf-RNA integrity index was calculated by using quantitative real-time RT-PCR assays of the small-sized fragment (106 bp) and the big-sized fragment (416 bp) in GAPDH mRNA. The initial analysis showed that cf-RNA was stable and detectable in the urine. The mean cf-RNA integrity index was significantly lower in the urine of ccRCC patients (mean: 0.07, 95%CI: 0.05-0.10) when compared with the urine from control subjects (mean: 0.25, 95%CI: 0.16-0.33) (p 0.001). The value of the area under the receiver-operating characteristic curve by using the cf-RNA integrity index for the diagnosis of ccRCC was 0.858 with a sensitivity of 68.0% and a specificity of 92.6%. Moreover, the small-sized VEGF mRNA fragment (98 bp) was detected in 31 of 50 urine samples of patients with ccRCC and in only 2 of 50 urine samples of control subjects (p 0.001) while the detection of the big-sized (420 bp) VEGF mRNA fragment was an infrequent event. Our findings suggest that the small-sized cf-RNA in urine was more abundant in cancer patients. The tumor-related gene VEGF mRNA fragment was detectable in the urine of cancer patients. Our finding may provide a new molecular assay for the diagnosis of renal cell carcinoma.

The expression of CXCR4 is implicated in the metastatic dissemination of different cancers. The information on its prognostic value has been very limited in clear cell renal cell carcinoma (ccRCC). Our objective was to explore the prognostic value of CXCR4 in ccRCC.104 patients with a ccRCC were studied. There were 69 men and 35 women with an average age of 64.5 years old (range: 34-86 years). The CXCR4 expression was evaluated by immunohistochemistry. The follow-up varied from 12 to 184 months with a mean of 79.5 months. Kaplan-Meier with a log rank test was performed to compare overall survival and cancer-specific survival after surgery. Univariate and multivariate analyses were performed according to the Cox regression model.CXCR4 expression was found in 68/104 (65.4%) of tumor samples. CXCR4 expression was located in the nucleus in 55/68 (80.8%) cases while cytoplasm or membrane location was found in 13/68 (19.2%) cases. High expression was found in 25/68 (36.8%) cases. During follow-up, 39 patients died, of which 26 died of cancer. Kaplan-Meier analysis revealed that a high expression of CXCR4 was associated with a reduced overall survival (p=0.017) and cancer-specific survival (p=0.022). Univariate analysis indicated that a high expression of CXCR4 was a significant factor for a poorer overall survival (p=0.020) and cancer-specific survival (p=0.027). By multivariate analysis, a high expression of CXCR4 appeared to be an independent factor of overall survival (p=0.024) and cancer-specific survival (p=0.028).This study suggested that a high CXCR4 expression was correlated with a worse outcome for ccRCC patients.

Primary central nervous system lymphoma (PCNSL) is a rare subtype of non-Hodgkin lymphoma (NHL) with extranodal location affecting only the CNS, meninges and eye, without visceral or lymph node involvement. Its incidence has increased sharply over the past three decades, especially in immunocompetent subjects. Most PCNSL cases are diffuse large B-cell lymphomas (DLBCLs). However, it differs from nodal DLBCL in that it has a worse prognosis. DLBCLs are a heterogeneous entity and according to new genomic discoveries, classifications into prognostic subgroups have been embarked upon. Two prognostic algorithms were then prepared using a panel of immunohistochemical markers (CD10, Bcl6, MUM1/IRF-4, and Bcl2), thus categorizing DLBCL into two subgroups, GCB (germinal centre B-cell-like) or non-GCB, and into Group 1 or Group 2. Our goal is to apply both of these two sub-classifications to 39 PCNSLs, in order to assess their usefulness and prognostic relevance. 74.3% of our PCNSLs were of a non-GCB phenotype, corresponding to an activated postgerminal origin. They were evenly distributed across G1 and G2. Two- and 5-year overall survival rates were 34.8% and 19.6%, respectively. Younger age (65) and a therapeutic combination of chemotherapy and radiotherapy significantly improved our patients' survival rates. The other clinical or biological markers tested had no prognostic impact. The two classifications did not reveal any significant survival difference. The recent discovery of a specific "transcriptional signature" of PCNSL, marking them out of DLBCL could account for the irrelevance of such prognostic classifications to PCNSL.

A retrospective study of adult autopsies and its value in a French university hospital.Despite its decline, the medical autopsy remains a major diagnostic tool to understand death mechanisms and to improve the quality of cares.Our purpose is to assess the current motivations of hospital autopsy demands, to analyze the concerned patients' medical characteristics, to determine the contribution of these with regard to the clinicians' questioning and to put the light on its limits.We reviewed the demands of adults' autopsies made in our hospital center between November 2005 and June 2008.Eighteen demands were sent during the considered period. More than half of these demands came from intensive care units, and had for main motivations to eliminate diagnostic hypotheses or to understand the fast lethal evolution in spite of the administered treatments. The median duration of hospitalization before death was about 12 days. The average age of the patients was about 61 years. These patients had suffered on average three important pathological histories before their admittance at the hospital, which were directly responsible for the death in 56% of the observations. The autopsy allowed to establish a diagnosis in 10 cases, to complete a diagnosis in five observations and to confirm a diagnosis in four cases. The absences of diagnoses are especially due to the fast degradation of the patients' state before the realization of the adapted additional examinations. The diagnostic errors concern pathologies with a poor specific or atypical semiology, or when there is one intricacy of important pathologies.The autopsy remains a contributory examination in the reviews of morbimortality and in the improvement of the care. However, for its results to be useful, they have to join a critical multidisciplinary discussion.

Giant atheromatous coronary aneurysms mimicking a cardiac tumor remain exceptional. We report the case of a patient who experienced a severe inferior myocardial infarction related to a giant thrombosed coronary aneurysm masquerading a cardiac tumor and compressing right cardiac cavities with mechanical detrimental consequences on tricuspid, mitral and aortic valvular competence. The contribution of imaging was essential to assess diagnosis, understand the physiopathogeny of myocardial and valvular consequences and plan the optimal surgical strategy.

Peroxisome proliferator activated receptor gamma (PPARgamma) involvement in thyroid tumorigenesis has recently been studied, especially in follicular neoplasms. Conflicting results concerning the regulation of this receptor in human papillary carcinoma have been reported. Therefore, we quantitatively assessed PPARgamma immunohistochemical expression in papillary carcinoma in comparison with other types of thyroid tumors and we evaluated its relationship with clinical criteria of aggressiveness.Immunohistochemistry (IHC) was performed on 56 human thyroid papillary carcinomas (PTC), 9 follicular carcinomas (FTC), 20 follicular adenomas (FA) and 18 Hürthle cells adenomas. PTC were divided into subgroups according to some aggressiveness criteria: tumor size, capsular invasion, lymph node metastasis. Immunostaining was semi-quantitatively analyzed using image analysis software.Strong nuclear PPARgamma expression was detected in a large number of PTC (42%), similar to that found in FTC (44%) or FA (63%). Only Hürthle cell adenoma showed a significantly lower proportion of PPARgamma-positive immunoreactivity (11%, p0.05). Cases of PTC-associated lymph node metastasis showed a higher percentage of PPARgamma-positivity than other case categories (63% vs. 20%), a result which was also noticed when comparing large PTC with infracentimentric tumors (60% vs. 39%, p0.05).These results, combined with recently published data, suggest that the intense PPARgamma immunostaining revealed in PTC could be related to high wtPPARgamma gene levels. Moreover, they corroborate a strong relationship between PPARgamma expression and tumor progression. PPARgamma IHC evaluation is not a valuable differential diagnostic tool for thyroid tumors but it could be a reliable marker of papillary carcinoma aggressiveness and a potential predictor for an eventual therapy by PPARgamma agonists.

Herein we reviewed the histopathological findings in 327 consecutive surgical specimens from patients with pharmaco-resistant epilepsy (PRE). Three major pathological groups (78.3% of all cases) were identified: Ammon's horn sclerosis (85 cases as an isolated lesion plus 18 as one part of a dual pathology), tumors (94 cases), and malformations (77 cases). Tumors, often associated with cortical dysplasias (CDs), were all of low histological grade and included 61 dysembryoplastic neuroepithelial tumors (DNTs), 29 gangliogliomas, and 4 pleomorphic xanthoastrocytomas (PXAs). Among the malformations were observed 52 CDs, 13 cavernomas, 8 cortical tubers, and 4 cysts. The remaining findings consisted of 16 scars (mostly post-traumatic) and 4 Rasmussen's encephalitis. Fifty-one (15.6%) specimens contained non-specific changes, and histological samples from 215 patients with presurgical implantation of electrodes revealed iatrogenic changes. All these figures are in agreement with the most recent and comparable series, and confirm the high incidence of DNTs that appear clearly as the most common tumoral entity in PRE. Our data also support the hypothesis of a close histogenetic relationship between DNT, ganglioglioma, and PXA, with a putative common origin from pluripotential progenitor CD34 positive cells of the subpial granular layer. As for CDs, our study confirms the clinical relevance of two main subtypes: severe CD (or Taylor's type CD) with neuronal cytomegaly and balloon cells, and non-Taylor's type CDs with a better outcome. Eventually, this series demonstrates that most patients have significant histopathological lesions, among which, aspects that are relevant to the diagnostic surgical pathologist are highlighted [published with a complete image database on CD-Rom].