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Bilateral laryngeal reinnervation can be a promising procedure for reanimation of laryngeal muscles, but currently not yet standardized. Besides patient conditions some intraoperative anatomical pitfalls need to be solved. Twelve human head and neck specimens (24 sides) have been studied using microdissection and histological serial sections of the nerves. The surgical anatomy of the dual reinnervation procedure according to JP Marie was investigated notably the branching pattern of the phrenic nerve (PN), the Ansa cervicalis (AC) and the recurrent laryngeal nerve (RLN). Despite variations of the AC, a prominent inferior common trunk for sterno-hyoid and sterno-thyroid muscles can be used in more than 90% of the specimens. If the AC is missing because of previous surgery, the tiny nerve of the thyro-hyoid muscle can be used preferred. The PN display a double roots pattern from C3 to C4 cervical plexus in 50% of the specimens. A single root pattern can be found and an end-to-lateral neurorraphy can be used. Intra-laryngeal nerves pattern of the RLN display tiny collaterals which cannot be selected for abduction–adduction activity. Direct implantation of the Y-shape great auricular nerve within the posterior crico-arytenoid muscles can be a reliable method leading to challenging mechanical and functional conditions. Several anatomical pitfalls, including intra-operative choices and variants of the donor nerves, but also the challenging intra-laryngeal dissection of the inferior laryngeal nerve need to be solved. A successful laryngeal reinnervation still needs further studies for a simplified procedure.

The signal transducer and activator of transcription 6 (STAT6) is implicated in the pathogenesis of some lymphomas including primary central nervous system lymphomas (PCNSLs). The aim of this study was to investigate STAT6 expression and clinicopathologic features in 25 PCNSLs using immunohistochemistry with 2 different anti-STAT6 antibodies. One (YE361) recognizes the C-terminus domain of the STAT6 protein and the other (Y641) recognizes the phosphorylated form of the protein. The phosphorylated STAT6 form was not expressed in any of the cases studied whereas the YE361 STAT6 showed only cytoplasmic expression in 14 (56%) cases. This expression did not correlate with age, prognostic score, multiplicity, invasion of deep structures, response to treatment, disease recurrence, overall survival, or BCL6, BCL2, PD-L1, and CD8 expression. A STAT6 expression score showed a trend for correlating with clinical performance status. It also showed a positive correlation with MYC expression. Thus, the phosphorylated form of STAT6 was not found in the current series, while the YE361 STAT6 showed only cytoplasmic expression and was associated with expression of MYC.

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.

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.

Malignant mesothelioma (MM), the primary cancer of the mesothelium, is characterized by dismal prognosis. However, there are other forms of primary mesothelial tumors, which are benign, the adenomatoid tumors (AT) and the well-differentiated papillary mesothelial tumor (WDPMT, formerly called well-differentiated papillary mesothelioma) (1). Interestingly, two recent studies showed that both ATs and WDPMTs harbor mutations in the TRAF7 (2,3), suggesting a possible pathogenetic link between them (1). The authors further proposed that as a possible consequence of this mutation, the L1 cell adhesion molecule (L1CAM), should be expressed in these lesions (2,3). Indeed, after performing immunohistochemistry for this marker, they showed L1CAM expression in both ATs and WDPMTs. Another lesion that could enter the family of benign mesothelial lesions, is the so-called "multicystic mesothelioma" (4). The exact nature of this lesion, reactional or neoplastic, has been a matter of debate since decades, and their varied terminology does prove the uncertainty (4). Given their common mesothelial origin, we aimed to explore the possible expression of L1CAM in a large series of cystic mesothelial lesions.

White adipose tissue browning has emerged as a putative therapy of obesity, and studies in mice have shown that Cdkn2a is implicated in white-to-brown transition. However, the role of Cdkn2a product p16 has been never studied in human brown fat tissue. The aim of the study is to investigate the expression of p16 in normal brown fat and in hibernoma, a lipoma containing brown fat-like adipocytes. Ten normal brown fat tissues and 5 hibernomas were immunohistochemically studied for p16 expression. Nearby white adipose tissue was used for comparison. All brown fat and hibernomas specimens express p16 in a cytoplasmic manner. Neighboring white adipose tissue is negative for p16 expression. Thus, cytoplasmic p16 may be associated with fat tissue browning.

Crystal-storing histiocytosis is a rare condition that is histologically characterized by intracellular cytoplasmic crystalline inclusions. It usually presents monoclonal immunoglobulins that deposit within histiocytes, which accumulate and affect different organs of the human body and are commonly associated with lymphoproliferative conditions, especially those with plasmacytic differentiation. The prognosis of this condition is variable and related to the underlying clinical disease. In this review article, we aim to describe and discuss the clinical and pathological characteristics of crystal-storing histiocytosis based on the available literature and to provide a thorough differential diagnosis.

Positron emission tomography/computed tomography (PET/CT) has shown prognostic significance in head and neck cancer patients. The underlying pathologic features that could explain the mechanisms associated with this observation are not clear. To analyze the correlation between 18-F-fluoro-2-deoxy-D-glucose (18F-FDG) uptake assessed by PET/CT in head and neck cancer and histopathologic prognostic factors. Ninety-nine patients with laryngeal and pharyngeal squamous cell carcinoma were retrospectively reviewed for pretreatment PET/CT measurements, namely standardized uptake value (SUV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). The corresponding histologic material was evaluated for tumor stroma-related prognostic factors such as the amount and type of stroma, lymphocytic response, tumor budding activity, and size of tumor cell nests in the tumor core area and tumor front. TLG and MTV were associated with tumor localization, as they were higher in oropharyngeal tumors. These values were also associated with tumor cell nest size in the tumor core with higher values corresponding to tumors with smaller nests. MTV40% was marginally associated with fibroblastic stroma type and higher budding activity. SUVmax was not associated with the histological factors in the whole sample, but higher values trended with higher tumor budding activity and stroma-rich tumors of the oropharynx. 18F-FDG PET measurements in head and neck squamous cell carcinomas are associated with prognostic histopathologic factors and suggest a possible correlation of glucose metabolism to epithelial-to-mesenchymal transition.

Primary central nervous system lymphoma (PCNSL) is an aggressive and rare disease. Autophagy is a catabolic mechanism boosting various tumors, including lymphomas; its inhibition is thus a promising therapeutic target. Its presence has never been studied in PCNSLs. We conducted a retrospective immunohistochemical study of 25 PCNSLs for LC3B, p62, and M6PR, comparing it with clinicopathological characteristics. Fourteen (56%) and eleven (44%) PCNSLs were of low and high LC3B expression, respectively. p62 expression was present in most tumors (n = 21, 84%). M6PR was present in all tumors, with 14 (56%) and 11 (44%) cases being of low and high M6PR expression, respectively. LC3B expression was correlated with the performance status (PS) (p = 0.04). No association was found with other clinical parameters, such as deep structure invasion, multiple lesions, complete response, and recurrence after response. p62 showed a strong positive association with MUM1 expression (p = 0.0005). M6PR expression showed a positive correlation (p = 0.04) with PD-L1 expression. No association was found with p53, Ki67, CD8, BCL2, BCL6, or double MYC/BLC2 co-expressors. No association of LC3B, p62, and M6PR expression with survival was found. Our findings provide evidence for the possible presence of autophagic markers in PCNSLs and, thus, for possible treatment targets.

Simple Summary Chordoma patients may be amenable to immunotherapy; however, the immune microenvironment of chordomas needs further investigation. We performed the immunohistochemical analysis of a chordoma series, showing that these tumors have a unique microenvironment characterized by the absence of PD-L1 tumor cell expression, but feature PD-L1+ immune cells playing a negative prognostic role. Abstract Chordomas are rare sarcomas that are usually treated by surgery and/or radiotherapy since these are chemo-resistant tumors, but immunotherapy could be a possible option for chordoma patients. However, few reports investigating the composition of the chordoma immune microenvironment exist. We immunohistochemically studied 81 chordomas regarding their immune microenvironment factors and compared them with clinicopathological data. Macrophages and CD4 cells were the most prominent inflammatory cell populations, followed by CD8 T cells, while CD20 B cells and high endothelial venules (MECA-79+) were less frequently found. PD-L1 (22C3) expression by inflammatory cells was found in 21 (26%) tumors and was associated with a larger tumor size. None of the cases showed the expression of PD-L1 by tumor cells. Survival analysis showed that younger patients had a better overall survival. Considering the immunohistochemical factors studied, higher CD8, the presence of PD-L1+ immune cells, and higher vascular density were adverse prognostic factors, but in multivariate analysis, only PD-L1+ immune cells retained prognostic significance. To conclude, chordoma tumor cells do not express PD-L1, but PD-L1+ immune cells seem to play a negative prognostic role, supporting the need for further studies in this field and the possible beneficial role of immunotherapy in these patients.

Background/aim In metastatic head and neck squamous cell carcinoma (HNSCC) the metastatic tumor does not always keep the same gene expression profile as the parental tumor, which may influence the course of the disease. The aim of this study was to compare the expression of genes implicated in HNSCC carcinogenesis between the primary tumor and the corresponding lymph node metastasis. Materials and methods Eighteen HNSCC, their corresponding node metastases and non-neoplastic tissues were studied by RT-qPCR for the expression of EGFR, VEGF, claudin7, maspin, survivin and SCCA. The levels of expression were correlated with histological characteristics and patients' prognosis. Results All genes except for survivin displayed different expression in node metastasis compared to the primary tumor. The expression of EGFR, survivin, maspin, and claudin7 in node metastasis and SSCA in the primary tumor affected the prognosis. SCCA expression is associated with the expression of claudin7 and maspin. P16-positive tumors expressed low levels of VEGF and SCCA, while keratinizing tumors over-expressed VEGF. Conclusion Differential gene expression levels in node metastases compared to the primary tumor is linked to the prognosis of HNSCC patients. The histological/immunohisto-chemical characteristics of the tumor are associated with these genes expression changes.

Simple Summary In contrast to normal notochords, autophagic factors are often present in chordomas. Furthermore, PD-L1+ immune cells also express LC3B, suggesting the need for further investigations between autophagy and the immune microenvironment. Abstract Chordomas are notably resistant to chemotherapy. One of the cytoprotective mechanisms implicated in chemoresistance is autophagy. There are indirect data that autophagy could be implicated in chordomas, but its presence has not been studied in chordoma tissues. Sixty-one (61) chordomas were immunohistochemically studied for autophagic markers and their expression was compared with the expression in notochords, clinicopathological data, as well as the tumor immune microenvironment. All chordomas strongly and diffusely expressed cytoplasmic p62 (sequestosome 1, SQSTM1/p62), whereas 16 (26.2%) tumors also showed nuclear p62 expression. LC3B (Microtubule-associated protein 1A/1B-light chain 3B) tumor cell expression was found in 44 (72.1%) tumors. Autophagy-related 16‑like 1 (ATG16L1) was also expressed by most tumors. All tumors expressed mannose-6-phosphate/insulin-like growth factor 2 receptor (M6PR/IGF2R). LC3B tumor cell expression was negatively associated with tumor size, while no other parameters, such as age, sex, localization, or survival, were associated with the immunohistochemical factors studied. LC3B immune cell expression showed a significant positive association with programmed death-ligand 1 (PD-L1)+ immune cells and with a higher vascular density. ATG16L1 expression was also positively associated with higher vascular density. Notochords (n = 5) showed different immunostaining with a very weak LC3B and M6PR expression, and no p62 expression. In contrast to normal notochords, autophagic factors such as LC3B and ATG16L1 are often present in chordomas, associated with a strong and diffuse expression of p62, suggesting a blocked autophagic flow. Furthermore, PD-L1+ immune cells also express LC3B, suggesting the need for further investigations between autophagy and the immune microenvironment.

Background The vasculature is a crucial factor in tumor development. Vascular co-option achieved by the L1 cell adhesion molecule (L1CAM) and lymphocyte recruitment inside tumors by high endothelial venules (HEVs) are important prognostic factors in primary breast cancer. Their status in breast cancer brain metastasis is unknown. Aim of the study To explore the status of L1CAMs and HEVs in this tumor compartment. Material and methods Thirty resected breast cancer brain metastases were immunohistochemically studied for L1CAM and MECA-79, an HEV marker. Clinicopathological factors were recorded. Results Age at brain metastasis diagnosis ranged from 37 to 80 years (median 55). The time to brain metastasis development after primary tumor diagnosis ranged from 12 to 187 months (median 57). Median overall survival after brain metastasis diagnosis was 29 months. None of the tumors expressed the factors studied. Conclusion L1CAM and high endothelial venules are not found in breast cancer brain metastasis.

Signal Transducer and Activator of Transcription 6 (STAT6), belonging to a family of seven similar members is primarily stimulated by interleukin(IL)-4 and IL-13, and acts as a T helper type 2 (Th2)-inducing factor. Thus, it is implicated in the pathophysiology of various allergic conditions, such as asthma, atopic dermatitis, eosinophilic esophagitis and food allergies, but also in tumor microenvironment regulation. Furthermore, certain forms of lymphomas, notably the Hodgkin lymphoma group, the primary mediastinal and primary central nervous system lymphoma, as well as some follicular and T cell lymphomas are associated with dysregulation of the STAT6 pathway. STAT6 immunohistochemical expression also serves as a surrogate marker in the diagnosis of solitary fibrous tumor, despite not directly responsible for the tumorigenic effect. These pathophysiological implications of the STAT6 pathway, its diagnostic or prognostic role in pathology, as well its immunohistochemical detection with different antibodies will be discussed in this review.

Objectives Chordomas are rare malignant tumors with a broad differential diagnosis, including chondrosarcomas and metastatic carcinomas. Recently, insulinoma-associated protein 1 (INSM1) has gained great interest regarding the diagnosis of neuroendocrine tumors but also extraskeletal myxoid chondrosarcomas. However, its expression in chordomas remains largely unknown. Methods We retrospectively examined 57 chordomas for INSM1 expression. Results INSM1 expression was found in only 5% of tumors. Conclusions This marker is rarely expressed in this type of tumor, raising questions about neuroendocrine differentiation.

Diagnosis of odontogenic tumors can be challenging due to their rarity and diverse morphology, but when arising near the tooth, the diagnosis could be suspected. When their location is not typical, like inside the paranasal sinuses, the diagnosis is less easy. Maxillary ameloblastomas are exceedingly rare with only sparse information on their epidemiological, histological and genetic characteristics. The aim of this report is to thoroughly review the available literature in order to present the characteristics of this tumor. According to available data, maxillary ameloblastomas can occur in all ages but later than mandible ones, and everywhere within the maxillary region without necessarily having direct contact with the teeth. No sex preference has been shown. The most common histological patterns seen in this location are the follicular and plexiform ones. Maxillary ameloblastomas are locally aggressive neoplasms, thus therapy aims for excision including normal bone beyond the lesion. In contrast to mandible ameloblastomas, maxillary ones most commonly show mutations of the SMO gene. Furthermore, differential tumor diagnosis is thoroughly discussed in the present review.

Background Tumors lymphocytic infiltration has prognostic and predictive value. However, the mechanisms involved in lymphocyte recruitment remain poorly characterized. High endothelial venules (HEV) are blood vessels specialized in lymphocyte recruitment, recently showing prognostic significance in some types of cancer. Their implications in laryngeal or pharyngeal cancer is largely unknown. Aim of the study To investigate the possible presence of HEVs in head and neck cancer. Material and Methods Oropharyngeal (n = 61), hypopharyngeal (n = 53) and laryngeal (n = 21) squamous cell carcinomas were immunohistochemically studied with the MECA-79 antibody, which specifically recognizes HEVs. Histological and clinical factors were correlated with HEVs’ presence. Results HEVs were present in 34% of tumors, showing significant correlations with oropharyngeal localization, higher lymphocytic response, lower tumor budding, lower T status, absence of distant metastases and better overall and progression-free survival. Conclusion HEVs represent an important prognostic factor in head and neck cancer.

Meningioma grading relies on several pathological criteria (brain invasion, mitotic count, sheeting, small cell foci, necrosis, macronucleoli and hypercellularity) and histopathological subtypes. Regardless of histopathological subtype, the presence of these pathological parameters can be focally present and not present on each slide of a meningioma. We performed (1) a retrospective work comparing the frequency of parameters used for meningioma grading between two periods with different sampling techniques, and (2) we calculated the probability of presence of each criterion on resected meningiomas entirely processed included and examined. First, we compared two time periods: between 2002-2008 where meningiomas were not all entirely sampled, and between 2012-2018 where all meningiomas were entirely sampled. The frequency of tumour grades was not significantly different between the two periods (p=0.17). Mitosis ≥4/1.6mm2, small cell foci, macronucleoli and hypercellularity were more frequently found when meningiomas were entirely sampled (p

BackgroundBrain metastases (Bmets) are frequent; however, limited data exist on the efficacy of immunotherapy in these lesions. The aims of the study were to analyze the immunohistochemical expressions of programmed death ligand 1 (PD-L1) and CD8 in Bmets and to compare them with their expressions in paired primary tumors, as well as correlate the results with clinicopathological features.MethodsThis is a retrospective study of 233 patients with Bmets and 111 paired primaries. Clinical, histological, and molecular data were recorded and compared with the immunohistochemical results of PD-L1 and CD8 expressions. The statistical analysis included χ2 test, Cramer’s V test, factorial analyses of variance, simple regression analysis, and Kaplan-Meier analysis with log-rank product limit estimation.ResultsPD-L1 expression was found in 23.6% of Bmets and in 29.0% of primary tumors with concordant expression between them in 75.5% of cases. Bmets PD-L1 expression was associated with primary tumor PD-L1 expression and the primary tumor type. Significant CD8 peritumoral expression was found in 68.6% of Bmets and in 87.7% of primary tumors. CD8 expression was concordant between primary and metastatic tumors in 73.3% of cases. Bmets CD8 expression was associated with primary tumor CD8 expression and primary tumor type. PD-L1 expression was associated with CD8 expression in both primary and metastatic tumors. The concordance between primary and metastatic tumor PD-L1 expression was independent of all factors studied. The concordance between primary and metastatic CD8 expressions was marginally associated to the time of Bmets development. No prognostic role for PD-L1 and CD8 expression in Bmets was found.ConclusionPD-L1 and CD8 Bmets expressions are associated with the primary tumor type and its PD-L1 and CD8 expressions. No factor predicts the discordance for PD-L1 expression, while time to Bmets development is associated with CD8 expression discordance.

Objectives The disruption or defect of the myometrium in the uterine scar of a cesarean section (CS) has been known by various names, such as uterine niche, isthmocele, deficient uterine scar, scar pouch, or diverticulum. Symptomatology, risk factors for niche development, and available treatment modalities have been recently studied. However, the histologic features of this disease remain unknown. Methods The histologic features of eight uterine niches are thoroughly described and a summary of the most important aspects of the uterine niche literature is provided. Five cases of CS scars without niche formation are comparatively examined. Results Most uterine niches harbor endocervical mucosa, often cystically dilated and/or an atrophic or disorganized endometrial mucosa of lower uterine segment origin. Regenerative epithelial atypia and fibroblastic stromal reaction are frequent features. No granulomatous reaction, important inflammation, or hemorrhage is seen. CS scars without niche formation do not harbor endocervical mucosa or inclusion cysts, fibroblastic stroma, or regenerative atypia. Conclusions As more prospective studies of uterine niche development and treatment will be conducted, a detailed pathologic report with the criteria proposed herein can be designed.

Tumor microenvironment has been extensively studied in various forms of cancer, like head and neck squamous cell carcinoma. Progress in the field revealed the prognostic significance of the various components of the tumor's ecosystem and led to changes in treatment strategies, like including immunotherapy as an important tool. In this chapter, the microenvironment of tumors with a special interest in laryngeal cancer will be described. The issues assessed include innate immune response factors, like neutrophils, neutrophil extracellular traps (NET), platelets, macrophages M1 or M2, dendritic cells, natural killer cells, as well as adaptive immunity aspects, like cytotoxic, exhausted and regulatory T cells, and immune checkpoints (PD-1/PD-L1, CTLA4). Also, stroma-associated factors, like fibroblasts, fibrosis, extracellular matrix, vessels and perineural invasion, hypoxia and cancer metabolism aspects, as well as the pre-metastatic niche, exosomes and cGAS-STING, are reviewed.

BACKGROUND The STAT6 pathway is implicated in the pathogenesis of various lymphomas; however, its immunohistochemical expression has not been fully investigated. Thus, the aim of this study was to investigate the immunohistochemical expression of the two forms of STAT6, phosphorylated or not, in a series of systemic lymphomas. MATERIALS AND METHODS Immunohistochemical expression of two antibodies, STAT6 (clone YE361) and pSTAT6 (clone Y641), which recognise the phosphorylated form of the molecule was studied in 60 lymphomas. RESULTS STAT6YE361 expression was cytoplasmic, with 23.3% of the cases showing high expression. pSTAT6Y641 expression was mostly nuclear and found in 45% of the cases. pSTAT6Y641 nuclear expression was associated with the lymphoma type (p

To investigate the impact of the volume of thyroid surgery and pathologic detection on the risk of thyroid cancer.We investigated the influence of the volume of thyroid surgery in a first study that included 23 384 thyroid surgeries and 5302 thyroid cancers collected between 2008 and 2013. Standardized incidence ratios (SIRs) and thyroid intervention rates (STIRs) were used as indicators of cancer risk and surgery volume, respectively. The influence of pathologic detection, using the number of cuts per gram of tissue as the indicator, was studied in a second study that included 1257 thyroid specimens, collected in 2014.We found departmental variations in SIRs and a significant effect of the STIR on the SIR (men, P = 0.0008; women, P0.0001). A 1/100 000 increase in the STIR resulted in a 3% and 1.3% increase in the SIR in men and women, respectively. This effect was greatest for microcancers and absent for tumours4 cm. The risk of cancer diagnosis was significantly associated with the number of cuts per gram of tissue (OR 6.1, P0.001), and was greater for total thyroidectomy than for lobectomy (P = 0.014) and when FNA cytology had been preoperatively performed (P0.001). The prevalence of incidental microcancers was highest in the centres performing the highest number of cuts per gram.The risk of thyroid cancer, particularly microcancer, is related to the volume of surgery and to the level of pathologist scrutiny. Both factors contribute to the increase in overdiagnosis. This further advocates for appropriate selection of patients for thyroid surgery.

Background Craniopharyngiomas and ameloblastomas show remarkable histologic and molecular similarities. The immune microenvironment of craniopharyngiomas has been recently studied showing interesting findings, while its composition in ameloblastomas is unknown. Similarly, some evidence of autophagic activity, a process of cellular constituents' degradation has been found in ameloblastomas, but no studies exist in craniopharyngiomas. Thus, the aim of the study is to compare factors of the immune microenvironment and the autophagic apparatus between these two tumor types. Methods 26 craniopharyngiomas and 14 ameloblastomas were immunohistochemically studied for PD-L1, CD8, CD20, S100, CD163, MECA-79, LC3B and p62. Results Craniopharyngiomas showed higher LC3B tumor cell expression, higher CD8+ T cells and higher CD163+ macrophages in comparison to ameloblastomas. LC3B tumor cell expression was associated with overall survival in craniopharyngioma patients and p62 nuclear expression was associated with overall survival in ameloblastoma patients. Conclusion This is the first study showing the presence of autophagic markers in craniopharyngiomas and describing the immune microenvironment of ameloblastomas.

Background Cardiac myxomas are rare, predominantly sporadic tumors that can cause heart failure and systematic inflammatory symptoms, and increase the risk of emboli. Their pathophysiology remains poorly understood, but intra-tumoral inflammation and senescence seem to be implicated in it. One of the principal cellular mechanisms implicated in tumor progression is autophagy, largely unknown in myxomas. Thus, our study aimed to investigate the presence of autophagic markers in myxomas and to correlate it with their immune microenvironment. Methods Twenty-five cardiac myxomas were studied for the autophagic markers LC3B and p62/sequestosome 1 and were compared with markers of the immune microenvironment. Results Most myxomas showed expression of both autophagic markers. We found a positive correlation between LC3B and PD-L1, as well as CD163, and a negative correlation between LC3B and CD8, CD20, CD138, and CD117 infiltration. Conclusion Our data not only confirm the presence of autophagic markers within cardiac myxomas but also suggest a possible association with their immune microenvironment.

Introduction Chordomas are rare malignant midline tumors, presumed to arise from notochordal remnants. This was further suggested by the discovery of the brachyury in chordomas pathogenesis. Its immunohistochemical expression has become the principal adjunct in the diagnosis of chordomas. However, studies about brachyury expression in chordomas are not fully comparable, mainly because they use different primary antibodies. Thus, the aim of this study is to investigate the expression of brachyury expression in a series of chordomas in conjunction to clinicopathological characteristics and to review the relevant literature providing all the details needed in the immunohistochemical study of brachyury. Materials and methods This is a retrospective study of 62 chordomas, diagnosed over a 22-year period. No dedifferentiated or poorly differentiated cases were included. A monoclonal primary antibody (clone A-4) was used and brachyury expression was evaluated by the H-score. Clinicopathological parameters studied were age, sex, tumor localization, decalcification status and tissue age. Fetal notochords were used for comparison. Results Mean H-score of nuclear brachyury expression was 129.8. The tissue age significantly influenced brachyury expression, the older samples expressing less brachyury. Decalcification demonstrated a trend to weaken brachyury expression. Clinical characteristics were not correlated with the patterns of brachyury expression. Notochords were negative. Literature review reveals several polyclonal antibodies used and a positivity of 75%–100% in chordomas with even more variable results in notochords. Conclusion In chordomas, as in other tumor types, an uniformization of studies about brachyury expression is needed, by considering the clone used, and the decalcification and the age of the sample, given the growing importance of brachyury in diagnosis and therapeutic steps.

Background FOXA1 is a major transcription factor involved in the action of human papilloma virus (HPV). However, it has been never studied in HPV-associated tumors. Aim of the study To investigate its expression in cervical and head and neck tumors. Material and methods 63 cervical carcinomas/dysplasias and 152 head and neck squamous cell carcinomas (HNSCC) were immunohistochemically studied for the expression of FOXA1. Results 63.1% of cervical SCC and 40.7% of endocervical adenocarcinomas strongly expressed FOXA1. Most (90%) pre-invasive lesions (CIN3 and in situ adenocarcinomas) strongly expressed FOXA1 and this difference from invasive lesions was statistically significant (p = 0.005). No association with clinicopathological factors was found. 51.3% of HNSCC expressed FOXA1. In these tumors, FOXA1 expression was associated with the non-keratinizing morphology but not with the HPV/p16 status neither other clinicopathological features. Of normal structures, salivary glands, endocervical glands and basal/parabasal cell layer of squamous epithelium of both uterine cervix and head and neck mucosa, all strongly expressed FOXA1. Conclusion FOXA1 is expressed by basal cells of squamous epithelium, pre-invasion lesions of the uterine cervix and the head/neck and almost half invasive cervical and head/neck carcinomas, supporting its possible implication in HPV pathogenesis.

// Georgia Karpathiou 1 , Francois Casteillo 1 , Jean-Baptiste Giroult 2 , Fabien Forest 1 , Pierre Fournel 4 , Alessandra Monaya 1 , Marios Froudarakis 3 , Jean Marc Dumollard 1 , Jean Michel Prades 2 , Michel Peoc'h 1 1 Department of Pathology, North Hospital, University Hospital of St-Etienne, St-Etienne, France 2 Department of Head and Neck Surgery, North Hospital, University Hospital of St-Etienne, St-Etienne, France 3 Department of Pneumonology, North Hospital, University Hospital of St-Etienne, St-Etienne, France 4 Oncology Institute Lucien Neuwirth, St-Etienne, France Correspondence to: Georgia Karpathiou, email: gakarpath@yahoo.gr Keywords: PD-L1, CTLA4, macrophages, dendritic cells Received: July 15, 2016 Accepted: December 02, 2016 Published: December 27, 2016 ABSTRACT Background: Immune system affects prognosis of various malignancies. Anti-immune pathways like PD-L1 and CTLA4 are used by the tumor to overcome immune system and they serve as immunotherapy targets. The immune microenvironment of head-and-neck squamous cell carcinoma (SCCHN) has not been sufficiently studied. Patients and Methods: 152 SCCHN were immunohistochemically studied for the expression of CD3, CD8, CD57, CD4, granzyme b, CD20, CD163, S100, PD-L1, CTLA4 and CXCR4. Results: CD3, CD8, CD57 and stromal S100 higher density is a good prognostic factor (p=0.02, 0.01, 0.02, 0.03 respectively). CTLA4 tumor expression is a poor prognostic factor (p=0.05). The rest immune cells do not affect prognosis. CD3 and CD8 density does not correlate with clinicopathological factors or p16/p53 expression, while CD57 and CD4 higher density is associated with the absence of distant metastases (p=0.03 and 0.07, respectively). Higher CD20 and S100 density is associated with lower T stage (p=0.04 and 0.03, respectively). PD-L1 expression is higher in CD3, CD8, and CD163 infiltrated tumors and in histologically more aggressive tumors. Response to neoadjuvant chemotherapy is better in highly CD3 infiltrated tumors and in tumors with less intraepithelial macrophages. Conclusion: Rich T-lympocytic and dendritic cell response is a good prognostic factor in SCCHN, whereas tumors expressing CTLA4 show poor prognosis. PDL1 expression does not affect prognosis, but it is expressed in histologically more aggressive tumors and in T-cells rich tumors. Response to induction chemotherapy is better in tumors less infiltrated by macrophages and mostly infiltrated by T cells.

Chordomas are rare osseous tumors believed to originate from notochordal remnants through brachyury activation. CDX2 and FOXA1 are both induced by brachyury, but their expression has not been studied in chordomas. We retrospectively studied the immunohistochemical expression of these two factors in 57 chordomas, finding that CDX2 is not expressed in these tumors. FOXA1 expression was found in 7 (12.3%) tumors. No association of FOXA1 expression with clinical factors was found. Thus, CDX2 expression is not a feature of chordomas, while a limited expression of FOXA1 is seen.

Objectives: Induction chemotherapy (IC) is occasionally used in head and neck cancer, leading to less extensive surgery and reduced need for irradiation. Factors predicting the response to IC have not been determined. In this study, we investigated the clinical and histopathologic factors that predict the response to IC. Methods: Head and neck squamous cell carcinomas from 81 patients were analyzed; clinical factors, histologic parameters, and expression of p16 and p53 were correlated with response to chemotherapy and prognosis. Results: Factors predicting a good response to IC were the nonoropharyngeal localization, a rich lymphocytic tissue response, and a low platelet-to-lymphocyte blood ratio before treatment. Response to IC did not correlate with prognosis, whereas a low neutrophil-to-lymphocyte ratio (NLR), the absence of a desmoplastic reaction, a rich lymphocytic tissue response, and the overexpression of p53 were associated with better prognosis. Conclusions: Lymphocytic tissue response, NLR, and nonoropharyngeal localization are factors predictive of response to IC.

The aim of the present study was to evaluate the thyroarytenoid muscle response during bilateral thyroid surgery using vagal nerve stimulation. 195 patients (390 nerves at risk) underwent a total thyroidectomy. The recurrent laryngeal nerve’s function was checked by analyzing the amplitude and the latency of the thyroarytenoid muscle’s responses after a vagal nerve’s stimulation (0.5 and 1 mA) using the NIM3 Medtronic system. All patients were submitted to preoperative and postoperative laryngoscopy. 20 patients get no thyroarytenoid muscle response to the vagal nerve stimulation, and 14 postoperative recurrent laryngeal nerve palsies were confirmed (3.8 %). Two palsies were present after 6 months (0.51 %). All the patients with muscle’s response have normal mobility vocal fold. The test sensitivity was 100 % and the test specificity was 98 %. Physiologically, the mean latencies of the muscular potentials for the right RLN were, respectively, 3.89 and 3.83 ms (p > 0.05) for the stimulation at 0.5 and 1 mA. The mean latencies for the left RLN were, respectively, 6.25 and 6.22 ms for the stimulation at 0.5 and 1 mA (p > 0.05). The difference of the latencies between the right and the left nerve was 2.30 ms (1.75–3.25 ms) with a stimulation of 0.5 or 1 mA (p

Background Granular cell tumor (GCT) remains a diagnostic clinicopathologic problem because the exact frequency of its detailed morphological and clinical characteristics is unknown as most observations are collected from small series or isolated cases. Herein, our aim is to highlight the frequency of all clinicopathological characteristics of this rare tumor based in our series and the available medical (PubMed) literature. Material and Methods 42 cases were evaluated for: tissue layers involved by the tumor (in skin and mucosae), growth pattern, nuclear pleomorphism, mitotic index, necrosis, spindling, calcification, hyalinization, and pustule-ovoid bodies of Milian, as well as perineural and vascular invasion, and the presence of adjacent epithelium changes, and lymphocytes and eosinophils infiltration., Follow-up was analyzed. The tumors were subclassified into benign, atypical and malignant according to Fanburg-Smith criteria and into benign or GCT of uncertain malignant potential according to Nasser criteria. The same characteristics were analyzed for 1499 cases reviewed according to PRISMA guidelines. Results In the current series, the mean age at diagnosis was 45.8 years (range 6–69 years). Most patients were females (60 %) and the involved organs were by descending frequency: skin and subcutaneous tissue, bronchus, esophagus, breast, tongue, larynx, pharynx, gingiva, trachea, right colon, vulva, and hypopharynx. No recurrence or progression was seen, despite 32 cases were incompletely excised, with the exception of one malignant tumor. The growth pattern was either infiltrative (85.71 %) or well limited (7.14 %). Sixteen tumors had vesicular nuclei. Mitotic activity was found in two tumors. Lymphocytic infiltration was found in 14 tumors. Eosinophils were present in 6 cases. One GCT of the right colon showed extensive calcification and hyalinization. Perineural invasion was noted in 6 lesions. No vascular invasion was found. One tumor was clinically malignant and the patient died 2 years after diagnosis. Medical literature review showed similar results in terms of frequency of the reported clinical and morphological features. Among cases with available follow up, almost 20 % showed positive margins and of those 20 % developed local recurrence. According to the Fanburg-Smith criteria, 72 % would be benign, 17 % atypical and 11 % malignant tumors, while according to those of Nasser, 93 % would be benign and 7% of uncertain malignant potential. However, true malignancy, as affirmed by metastasis of GCT is found in almost 2.5 % of the cases. Conclusion GCT is a usually benign tumor, affecting any anatomic location. Necrosis and mitotic activity seem to be the most effective histologic criteria for detecting aggressive tumors, but the presence of metastasis (2.5 % of the cases) remains the most accepted definitive criterion for diagnosis of malignant GCT.

BACKGROUND Despite immune microenvironment of head and neck squamous cell carcinoma (HNSCC) has been studied, there are no sufficient data on the role of tumor stroma factors. The aim of the study was to explore the prognostic and predictive role of these factors in a large series of HNSCC. METHODS This is a retrospective study of 266 patients with laryngeal and pharyngeal SCC. Clinical data were correlated with the following histological parameters: tumor-stroma ratio (TSR), tumor budding activity (BA), cell nests size (CNS), and stroma type. RESULTS Stroma-rich tumors, tumor budding, smaller CNS at core and front area, and fibroblastic stroma type, were all adverse prognostic factors (P

Purpose: A reliable experimental measurement of endothelial cell (EC) viability is paramount in the assessment of new drugs, devices, and surgical processes liable to damage the corneal endothelium, as well as during endothelial bioengineering. We previously used triple Hoechst–Ethidium–Calcein-AM labeling coupled with image analysis to determine the viability and mortality of ECs on the whole cornea, thus defining the new notion of viable EC density. To make it accessible to all, and for improved reproducibility, we have now developed an ImageJ plugin with improved thresholding algorithms. Methods: The CorneaJ plugin comprised contrast improvement, regional selection of pixels with similar gray levels, simplified thresholding facilitated by a user-friendly images display, and the option of manual touch-up to increase accuracy. After Hoechst–Ethidium– Calcein-AM labeling, the endothelium of 10 human corneas was observed with a fluorescent microscope with motorized stage. The performance of CorneaJ was compared with standard manual thresholding: accuracy was determined by comparison with fully manual selection of viable ECs by an expert; and reproducibility, by calculating the intraclass coefficient and coefficient of variation (100 · SD/mean) of 7 independent observers. Results: CorneaJ was more accurate than the standard thresholding, with a deviation from the expected value of 21.8% [95% confidence interval (CI), 22.7 to 20.9] versus 6.0% (95% CI, 2.8–9.3), respectively, P , 0.001. It was also more reproducible, with an intraclass coefficient of 0.98 (95% CI, 0.954–0.994) versus 0.81 (95% CI, 0.628–0.937) and a mean coefficient of variation of 2.6 (1.4–7.4) and 5.7 (3.4–19.8), P = 0.005. Conclusions: CorneaJ is a new, fast, and reproducible free image analysis tool that could help standardize experimental measurement of corneal EC viability.

The control of corneal transparency depends on the integrity of its endothelial monolayer, which is considered nonregenerative in adult humans. In pathological situations, endothelial cell (EC) loss, not offset by mitosis, can lead to irreversible corneal edema and blindness. However, the hypothesis of a slow, clinically insufficient regeneration starting from the corneal periphery remains debatable. The authors have re-evaluated the microanatomy of the endothelium in order to identify structures likely to support this homeostasis model. Whole endothelia of 88 human corneas (not stored, and stored in organ culture) with mean donor age of 80 ± 12 years were analyzed using an original flat-mounting technique. In 61% of corneas, cells located at the extreme periphery (last 200 μm of the endothelium) were organized in small clusters with two to three cell layers around Hassall-Henle bodies. In 68% of corneas, peripheral ECs formed centripetal rows 830 ± 295 μm long, with Descemet membrane furrows visible by scanning electron microscopy. EC density was significantly higher in zones with cell rows. When immunostained, ECs in the extreme periphery exhibited lesser differentiation (ZO-1, Actin, Na/K ATPase, CoxIV) than ECs in the center of the cornea but preferentially expressed stem cell markers (Nestin, Telomerase, and occasionally breast cancer resistance protein) and, in rare cases, the proliferation marker Ki67. Stored corneas had fewer cell clusters but more Ki67-positive ECs. We identified a novel anatomic organization in the periphery of the human corneal endothelium, suggesting a continuous slow centripetal migration, throughout life, of ECs from specific niches.

Resume Le declin de l’autopsie medicale, malgre la reconnaissance incontestee de son utilite, n’est plus a prouver. En reprenant l’encadrement juridique de cet acte d’exception, nous avons tente d’identifier les indications, les contre-indications, les precautions d’emploi, les limites, les contraintes techniques, juridiques et ethiques et les couts de cet outil diagnostique et therapeutique. Il ressort de la discussion que le principal frein a la realisation des autopsies pourrait etre son encadrement juridique trop strict.

International audience; Forensic pathologists are sometimes confronted with microscopic foreign bodies mixed in with soft tissues surrounding wounds and which are thus difficult to identify. This identification, however, could be primordial in investigating a crime and in determining the weapon used. A case of a fatal respiratory distress syndrome due to conjoining suicidal drug intoxication and laryngeal obstruction by a voluminous foreign body giant cell granuloma is presented. The classical histological examination showed exogenous particles in the vocal cord tumor with birefringent qualities. Their analysis with Fourier-Transform infrared (FTIR) spectrometry coupled with infrared microscope allows the determination of their chemical nature as polytetrafluoroethylene and to the diagnosis of teflonoma. This case report put the emphasis on the forensic interest of the FTIR imaging.

Purpose To quantify cell survival and tissue structure preservation of porcine cornea stored in a bioreactor (BR) that recreates a transcorneal pressure gradient equivalent to intraocular pressure (IOP) and renews the medium. Methods A BR comprising endothelial and epithelial chambers was machined in a biocompatible material. The porcine cornea, securely held, separated the chambers. Medium flow and pressure inside the endothelial chamber were maintained by a peristaltic pump. In the epithelial chamber, the corneal surface was alternatively exposed to air and a specific medium. Two transparent windows allowed thickness measurement by optical coherence tomography without opening the BR. Porcine corneas stored in the BR-on (pressure 20 mm Hg, flow 5 μL/min, temperature 31°C) were compared with (1) BR-off (no pressure or flow); (2) organ culture; and (3) Petri dish with agar on the endothelial side. Epithelial and limbal structure and differentiation, corneal transparency and thickness, and endothelial viability were compared after 7 days of storage and with fresh corneas. Results Corneas stored in the BR-on were thinner and more transparent than those stored with the other methods. The BR-on preserved a stratified and differentiated (K3/K12+) corneal epithelium and undifferentiated basal limbal cells with stemness markers (K3/K12-; ABCB5, K14, p75+), as well as endothelial integrity. Conclusions By recreating equivalent IOP and medium renewal, the BR obtained unprecedented storage quality of porcine corneas and preserved their main epithelial, limbal, and endothelial characteristics.

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 (

Since the seminal work of M. Hirano, which defined the three-layered lamina propria of the human vocal fold, there has been confusion in the labeling of each layer. Recent studies described the composition of fibers and interstitial molecules within the lamina propria leading to various biomechanical properties. However, collagen fibers appear as the most important structure component. We used an optical analysis and the picrosirius-polarization method to describe collagen fibers from six adult and two fetal human larynges fixed in formalin and frontally sectioned in the middle part of the vocal fold. The deep layer of the lamina propria is the most densely organized band of collagen fibers penetrating the superficial muscle bundles of the vocal muscle. The mean thickness of this layer is about 36% of the lamina propria and shows a network of strongly birefringent fibers (collagen type I and III). The superficial layer of the lamina propria is a narrow band of collagen fibers immediately below the basement membrane of the epithelium. The mean thickness of this layer is about 13% of the lamina propria and shows strong birefringent fibers. The intermediate layer is the less densely organized band between the deep and superficial layers. The mean thickness of this layer is about 51% of the lamina propria and shows clear, green weakly birefringent fibers characterized as collagen type III. The fetal lamina propria contains only a monolayer distribution of loose collagen fibers between the epithelium and the vocal muscle. These results help describe the distribution of collagen fibers within the lamina propria of the human vocal fold and have implications to understand the cover-body theory of voice production both in the adult and newborn.

Resume Introduction En depit de son declin, l’autopsie medicale reste un outil diagnostique et pedagogique majeur, indispensable a la comprehension des causes et des mecanismes de deces ainsi qu’a l’amelioration de la qualite des soins. Objectifs Notre etude a pour objectifs de cerner les motivations actuelles des demandes d’autopsies hospitalieres, d’analyser les caracteristiques medicales des patients, de determiner l’apport des resultats autopsiques aux interrogations des cliniciens et de mettre en evidence ses limites. Materiel et methode Nous avons analyse de maniere retrospective les demandes d’autopsies d’adultes etablies au CHU de Saint-Etienne entre novembre 2005 et juin 2008 ainsi que les conclusions des comptes rendus correspondants. Resultats La periode consideree a fait l’objet de 18 demandes dont dix emanent des services de reanimation. Leur but etait d’eliminer certaines hypotheses diagnostiques ou de comprendre une evolution letale rapide malgre le traitement. La duree mediane d’hospitalisation avant le deces est de 12 jours et l’âge moyen des patients est de 61 ans. Lors de leur admission, ils presentent en moyenne trois antecedents pathologiques importants et directement responsables du deces pour 56 % d’entre eux. L’autopsie a permis de poser le diagnostic dans dix cas, de le completer dans cinq cas et de confirmer les suspicions cliniques dans quatre cas. La rapide degradation de l’etat des malades avant la realisation d’examens complementaires adaptes explique majoritairement l’absence de diagnostic. Les erreurs diagnostiques concernent des affections de semiologie peu specifique ou atypique ou en cas d’intrication de pathologies lourdes chez un meme sujet. Conclusion L’autopsie continue a apporter une incontestable contribution a l’amelioration des soins et aux travaux portant sur la morbidite et la mortalite. Pour etre utiles, ses resultats doivent obligatoirement s’inscrire dans une discussion multidisciplinaire critique.