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The current study aimed to identify and validate an applicable immunohistochemistry panel including Ki-67, c-MYC, estrogen receptor-α (ER-α), and progesterone receptor isoforms A/B (PR-A/B) in correlation with clinicopathological parameters in patients affected by deep infiltrating endometriosis. Tissue microarrays were prepared from a cohort of 113 patients. Phenotypic profile of the panel molecules was evaluated in glands and stroma in parallel with microvessels and stroma density measurements. Principal component analysis was performed on 8 immunohistochemical variables, 2 histological variables, and 8 subgroups of clinical parameters. The immunohistochemical profiling showed consistent Ki-67 immunostaining in 17.9% of the samples and c-MYC in 83.1%, while intense ER-α immunoreactivity was detected in 84% of the samples and PR-A/B isoforms in 24.1% of them. The combination of clinical parameters and tissue phenotype allowed a stratification of endometriosis-affected patients. Such novel phenotypical and clinical correlation could be helpful in the future studies for a better stratification of the disease aiming at a personalized patient care., (© The Author(s) 2016.)

Deep infiltrating endometriosis (DIE) is a particular clinical and histological entity of endometriosis responsible for chronic pelvic pain and infertility. Here we characterize the proliferative phenotype of DIE cells, to explore the cellular and molecular mechanisms that could explain their aggressive potential. In addition, the inhibition of mTOR/AKT pathway was tested, as a potential treatment of DIE. Included were 22 patients with DIE and 12 control patients without endometriosis. Epithelial and stromal cells were extracted from biopsies of eutopic endometrium and deep infiltrating endometriotic nodules from patients with DIE. Cell proliferation was determined by thymidine incorporation. Oxidative stress was assayed by spectrofluorometry. The ERK and mTOR/AKT pathways were analyzed in vitro by Western blot and for AKT in vivo in a mouse model of DIE. The proliferation rate of eutopic endometrial cells and of deep infiltrating endometriotic cells from DIE patients was higher than that of endometrial cells from controls. The hyperproliferative phenotype of endometriotic cells was associated with an increase in endogenous oxidative stress, and with activation of the ERK and mTOR/AKT pathways. mTOR/AKT inhibition by temsirolimus decreased endometriotic cell proliferation both in vitro and in vivo in a mouse model of DIE. Blocking the mTOR/AKT pathway offers new prospects for the treatment of DIE., (Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Deep infiltrating endometriosis (DIE) is characterized by chronic pain, hyperproliferation of endometriotic cells and fibrosis. Since cannabinoids are endowed with antiproliferative and antifibrotic properties, in addition to their psychogenic and analgesic effects, cannabinoid agonists have been evaluated in DIE both in vitro and in vivo. The in vitro effects of the cannabinoid agonist WIN 55212-2 were evaluated on primary endometriotic and endometrial stromal and epithelial cell lines extracted from patients with or without DIE. Cell proliferation was determined by thymidine incorporation and production of reactive oxygen species by spectrofluorometry. ERK and Akt pathways were studied by immunoblotting. Immunoblotting of α-smooth muscle actin was studied as evidence of myofibroblastic transformation. The in vivo effects of WIN 55212-2 were evaluated on Nude mice implanted with human deep infiltrating endometriotic nodules. The in vitro treatment of stromal endometriotic cells by WIN 55212-2 decreased cell proliferation, reactive oxygen species production, and α-smooth muscle actin expression. The decrease in cell proliferation induced by WIN 55212-2 was not associated with a decrease in ERK activation, but was associated with the inhibition of Akt activation. WIN 55212-2 abrogated the growth of endometriotic tissue implanted in Nude mice. Cannabinoid agonists exert anti-proliferative effects on stromal endometriotic cells linked to the inhibition of the Akt pathway. These beneficial effects of cannabinoid agonists on DIE have been confirmed in vivo.

Endometriosis affects 6-10% of women in their reproductive years, causing chronic pelvic pain and infertility. Its pathogenesis remains poorly understood and current treatments, based on hormonal therapy or surgery, are often insufficient. The purpose of our study was to investigate the role of the ERK pathway in the development of endometriosis and to test the effects of protein kinase inhibitors on the proliferation of endometriotic cells in vitro and in vivo. We studied ex vivo human endometrial and endometriotic cells in culture. Stromal and epithelial cells were extracted from endometrial and endometriotic biopsies from patients with endometriosis and from patients without endometriosis. The ERK pathway was explored by western blot on cell lysates and by ELISA on total crushed specimens of endometrium. Cells in culture were treated with A771726, PD98059, and U0126. Human endometriotic lesions were implanted in nude mice. Mice were treated with A771726, leflunomide, PD98059, U0126 or PBS during 2 weeks before sacrifice and extraction of the endometriotic implants for histological examination. We found that the ERK pathway was significantly activated in endometriotic cells and in endometrial cells from patients with endometriosis compared to endometrial cells of control patients, both by ELISA and by western blot. This phenomenon was associated with an increased proliferation of endometriotic cells compared to endometrial cells. Treating endometriotic cells with A771726, PD98059 or U0126 abrogated the phosphorylation of ERK and significantly decreased the cellular proliferation in vitro. In vivo, A771726, leflunomide, PD98059, and U0126 controlled the growth of endometriotic implants in the mouse model of endometriosis. Our study shows that protein kinase inhibitors could be new candidates to treat endometriosis. However, further studies are needed to evaluate their effects and tolerability in humans., (Copyright 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Objective: We conducted a prospective study to assess the long-term results of complete surgery for low rectal endometriosis (LRE), paying particular attention to surgical complications, functional results, and disease recurrence after a follow-up of at least 5 years., Summary Background Data: Deep infiltrating endometriosis (DIE) may infiltrate the midlow rectum and lead to severe pelvic pain. Complete resection of LRE is reluctantly considered by young women of childbearing age., Methods: From 1995 to 2003, 100 women with severe pelvic pain and previous incomplete surgery (n=82) underwent complete open surgery for LRE after thorough preoperative imaging work-up. This included total or subtotal rectal excision with combined resection of all extrarectal endometriotic lesions. Univariate analysis of predictive factors for transient neurogenic bladder and surgical complications was performed. Mean follow-up was 78+/-15 months., Results: All patients underwent rectal resection with straight coloanal (n=16) or low colorectal anastomosis (n=84). A concomitant extrarectal procedure was required in all instances, including gynecologic procedures (n=100), additional intestinal (n=45), and urologic (n=23) resections. A fertility-preserving procedure was possible in 92% of the patients. Mean numbers of DIE and endometriotic lesions were 3.9+/-1.4 and 5.5+/-1.6 per patient, respectively. There were no deaths and the surgical morbidity rate was 16%. Sixteen patients developed a transient peripheral neurogenic bladder, which was more frequently observed after colonanal anastomosis (P<0.001) or concomitant hysterectomy (P<0.01) and in patients with more than 4 DIE lesions (P<0.05). At last follow-up, 94 patients had complete (n=83) or very satisfactory (n=11) relief of symptoms. Urine voiding and fecal continence was satisfactory in all cases. There was no recurrence of colorectal and/or urologic endometriosis and the overall DIE recurrence rate was 2%., Conclusions: Complete surgery for LRE provides excellent long-term functional results in 94% of the patients, provided all extraintestinal endometriotic lesions are resected during the same surgical procedure. In that setting, the overall 5-year recurrence rate is very low.

Background: Non-bacterial thrombotic endocarditis is a severe complication of cancer, rarely reported in gynecologic tumors. However, it can be inaugural and lead to complex diagnostic pathways., Case: A 40-year-old woman presented with a stroke, related to an endocarditis. The valvular vegetation was surgically removed, and a malignant node was resected. A PET-scan led to the diagnosis of a myometrial tumor, which was found to be a primitive neuroectodermal tumor (PNET). The patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy, and systemic chemotherapy which allowed a complete remission of tumoral and cardio-vascular symptoms., Conclusion: To our knowledge, this is the first case report of a PNET of the myometrium revealed by cardio-vascular symptoms.

Many articles concerning conventional Pap smears, ThinPrep liquid-based cytology (LBC) and Hybrid-Capture II HPV test (HC II) have been published. This study, carried out by the French Society of Clinical Cytology, may be conspicuous for several reasons: it was financially independent; it compared the efficiency of the conventional Pap smear and LBC, of the conventional Pap smear and HC II, and included an economic study based on real costs; for all the women, a "gold standard" reference method, colposcopy, was available and biopsies were performed whenever a lesion was detected; The conventional Pap smear, the LBC (split-sample technique), the colposcopy, and the biopsies were done at the same time. This study included 2,585 women shared into two groups: a group A of a high-risk population, a group B of a screening population. The statistical analysis of the results showed that conventional Pap smears consistently had superior or equivalent sensitivity and specificity than LBC for the lesions at threshold CIN-I (Cervical Intraepithelial Neoplasia) or CIN-II or higher. It underlined the low specificity of the HC II. Finally, the LBC mean cost was never covered by the Social Security tariff.

Sebaceous carcinoma is a rare tumor, from the adnexal epithélium of the sebaceous glands. Usually, lesions arise in meibonian glands of the eyelid. However, extraocular lesions within head and neck have been reported. We report a case of recurrent sebaceous carcinoma of the parotid gland without metastases.

Arrhythmogenic right ventricular dysplasia is a polymorphous clinical entity. Its diagnosis is difficult in incomplete forms or at the onset of the disease. The diagnosis is based on the association of clinical, electrocardiographic and electrophysiologic signs which are the result of a specific pathological structure, consisting of fibromuscular bundles isolated from each other by fatty tissue resulting from apoptosis and/or the basic dysplastic phenomenon. These fibers are oriented in a parallel direction and connected at their extremities with normal myocardium. These fibromyocyte bundles seem to constitute a tissue with preferential conduction, which could explain reentry phenomena, and therefore the basis for the pathogenesis of ventricular arrhythmias. The various clinical aspects of ARVD have similar morphological patterns, but a completely different prognosis and outcome.

Salivary gland carcinosarcoma is a rare neoplasm, with a poor prognosis, that should not be confused with the more common carcinoma ex-pleomorphic adenoma, in which the epithelial component alone is malignant. The authors report one case of carcinosarcoma of the submandibular gland, with no previous history of pre-existent tumor. The tumor exhibited two intermingled and very atypical cellular components, one undifferentiated and the other with a chondroid pattern. Immunostaining with epithelial markers in the undifferentiated area allowed to distinguish this tumor from salivary gland sarcomas. In addition, the positivity for EMA, vimentin, and S100 protein in the two predominant components suggested a common origin for the different tumoral cell types, and led to discuss the nomenclature and the still unclarified cellular origin of these tumors.

The histological examination of the salivary gland tumors is a very important step in the diagnostic approach of the lesions, on which depends the success of therapeutic outcome. Some surprises may occur; four examples were reported. In one case the lesion was not a tumor but a tuberculous lymphadenitis; another showed a Destombes Rosai Dorfman syndrome. Two other cases were found to be unusual tumors: a carcinosarcoma of the submandibular gland and a metastasis of a Merkel carcinoma in the submandibular gland.

This retrospective pathological study, based on twenty-nine glomus tumors, was conducted in order to define the histological or immunohistochemical diagnostic criteria in cases with atypical morphology. The immunohistochemical phenotype of glomus tumors was defined by means of identification of glomus cells, vessels and associated nerve fibres.

Neuroendocrine carcinomas of the larynx are rare and their links with thyroid neoplastic lesions are not specified in most reported cases. We report such a case secondary to medullary thyroid carcinoma. In a 63-year-old man, a supra glottic laryngeal carcinoma confirmed by biopsy was initially treated by chemotherapy. A second biopsy of the laryngeal lesion after incomplete remission displayed a neuroendocrine carcinoma with calcitonin in neoplastic cells. Laryngectomy, cervical bilateral neck dissection and thyroid isthmic adenoma dissection were performed. Numerous neoplastic cells from these tissues contained calcitonin revealed by immunohistochemical method. Calcitoninemia was highly increased and multiple bone metastases were discovered. Secondary total thyroidectomy was not possible and the patient died 6 months after. In this case the neuroendocrine laryngeal carcinoma was probably secondary to a latent medullary thyroid carcinoma. Medullary thyroid carcinoma is most often unknown in similar previously reported cases of neuroendocrine laryngeal carcinoma. Thus a neuroendocrine tumour of the larynx should require search for extra thyroid and over all thyroid neuroendocrine carcinoma, even limited to a small and latent lesion.

Modified subcutaneous mastectomy was described by one of us in 1968; its approach, the dissection of the gland, plastic reconstruction of shape and volume are completely different from the subcutaneous mastectomy performed by plastic surgeons. 3 different time periods were studied to explain clearly evolution in the technic and indications. During many years retrospective studies made it possible to build a procedure according to the new diagnostic means for infraclinical breast cancer and to the constant improving prosthetic material. Therefore our indications for modified subcutaneous mastectomy are as following: suspicious mastopathies are the best indications with a performing choice of the radiologic images which require histologic control some evolutive or evoluated mastopathies some small infiltrating tumors developing in a highly dystrophic glandular surrounding. The numerous in situ cancers accompanying them argue for this choice. some big phyllod tumors or phyllod's recurrences.

Elastofibroma is a rare tumor mainly found under the scapula. Based on a recent study of five cases, we would like to stress the importance of making the diagnosis of elastofibroma, as this lesion simply consists of dysplasia of the elastic fibres and is not malignant as could be suggested by clinical examination.

One hundred and seven breast cancers were studied by immunohistochemistry with a monoclonal antibody revealing a protein bound to cytosolic estrogen receptors ERD5 on paraffin embedded tissue. Seventy seven per cent of the cancers were positive with a variable intensity. In half of the cases, the estrogen cytosolic receptors were also determined by biochemistry. The results were similar in 74% of cases. Estrogen receptors were detected by immunohistochemistry in 18.5% of the cancers which were negative on biochemistry. As is well known, the presence of estrogen in 18.5% of the cancers which were negative on biochemistry. As is well known, the presence of estrogen receptors is an important prognostic factor in breast cancer. Our results, together with the simplicity of the immunohistochemical method, should encourage pathologists to include this analysis in the study of surgical specimens of breast cancers.

We report one case of pseudotumoral salivary location of the Rosai-Dorfman syndrome, with a favorable outcome, occurring in a 32-year-old man from Guadeloupe. The clinical, biological and clinicopathological features of this syndrome, as well as the pathogenetic hypotheses, are summed up. In this case, no bacterial, fungal, parasitic or viral agent was discovered. The subject presented with no immune abnormality likely to account for the persistence and intensity of the histiocytic infiltration with lymphophagocytosis associated to the lymphoplasmocytic infiltration. The rarity of ENT, and more specifically salivary, locations is emphasized. The importance of the detection of possible immune abnormalities in such patients is demonstrated by the outcome of the syndrome being more often unfavorable when such abnormalities are present.

A case clinically and morphologically typical angio-immunoblastic lymphadenopathy in a 64-year old man is reported. A sicca syndrome was discovered with histological localization in the labial accessory salivary glands. Death occurred after a course of a few months. The autopsy showed an association of angio-immunoblastic lymphadenopathy lesions of the bone marrow and the lymph node and of typical multivisceral localizations of Kaposi's sarcoma (lymph node, liver, thyroïdd gland) without skin involvement. This association of two diseases characterized by severe dysimmunity with B lymphocytes hyperplasia is discussed, and compared to the others diseases which could be associated with Kaposi's sarcoma.

A sixty-four year-old woman was admitted for chronic diarrhea with severe weight loss. Investigations showed hepatomegaly, positive serologic tests for syphilis, and nephrotic syndrome with proteinuria. Anasarca occurred and the patient died shortly after admission. Necropsy showed sclero-gummatous hepatic syphilis, generalized amyloïdosis and ulcerative colitis. These last two manifestations and their association with tertiary stage syphilis are discussed.

Invasion of the hyothyroepiglottic (HTE) space, or pre-epiglottic space, constitutes an important element in selecting the type of therapy in cancer of the larynx (functional surgery, radiotherapy), the oropharynx and the hypopharynx. Clinical examination and standard X-ray films provide insufficient information. High frequency real time ultrasonography offers a reliable means for exploring the pre-epiglottic space, as evidenced by this study carried on 34 histologically-confirmed cases taken among 77 cases of carcinoma of the upper digestive and respiratory tracts. Advantages presented by this method over CT-scanning and MR imaging in this particular pathological are simplicity, rapidity and low cost, combined with good performance.

Seemingly spontaneous subcutaneous ruptures of the flexor tendons of the hand are not frequently encountered. The case studied is that of a young man whose deep flexor tendon of the third finger snapped during a slight effort. The histological and immunohistochemical analysis led to the conclusion that there was localization of an intra-tendinous neurofibroma, which would seem to be a so-far undescribed phenomenon. The patient presented neurofibromas elsewhere and had pigmented spots on the body, which enabled Von Recklinghausen's disease to be diagnosed.

Two hundred cases of breast carcinoma were studied, with particular attention to adjacent non-malignant modifications considered by some authors as preneoplastic changes. Diverse proliferative lesions were recognized in 82% of cases. Atypical hyperplasia was present in 51.5% of cases and was more often ductal (83/200) than lobular (40/200). Microscopic cysts were noted in 72% of cases. Calcifications, easily identified by mammography were present in 20% of cases and were associated with atypical hyperplasia in 4/5 of cases. The mean of patients was 58 years. For comparative studies of histologic lesions the following age categories were evaluated: category I less than 50 years (57 patients), category II greater than or equal to 50 years (143 patients). Atypical lobular hyperplasia, adenosis, and, to a lesser degree, sclerosing adenosis and macroscopic cysts were more frequently associated with breast cancer in women younger than 50. Fibro-atrophic or lipomatous changes were more often found in the older group of women, as expected. Sclerosing adenosis was significantly more frequent in breasts with multifocal infiltrating carcinoma. Such changes must be considered as risk factors by pathologists when present in mammary specimens without carcinomatous lesions, and careful study should be undertaken to locate a possible in situ microscopic carcinoma. No differences appeared in lesions associated with breast cancer in women with or without a familial history of breast cancer.

In the case of breast cancer with no clinical signs, radiological signs are the decisive factors to indicate surgery, histological studies or treatment. Foci of microcalcifications currently are the feature to identify as a rule. However, they reveal canalicular carcinoma in only 1 case out of 3. We propose a radiological technique allowing the selection of the microcalcifications to be operated by means of the digitization of a mammographic film and of a software-controlled morphometric analysis. 10,000 microcalcifications have been studied in this way. The most reliable of the 12 parameters that were distinguished is compacity. 100 files were studied with conventional mammography and a morphometric and histological analysis. Any microcalcification less compact than 0.35 is highly suspicious, since this parameter is the only one having a significant difference, with a confidence interval of 95%. The patients are now selected in this way. Differences in the age of the lesions, multiple foci and sometimes lesions with multiple centers lead us to automatically propose the exeresis of the gland, followed by immediate reconstruction of its shape and volume. According to a retrospective study we carried out on 111 subclinical intracanalicular carcinomas after a 5 to 20-year time interval, recurrence is observe in only 4.5% of all cases.

Limited resection in partial surgery for carcinoma of the larynx leads to discussion of three surgical attitudes: total surgical resection as a matter of principle, additional treatment by radiotherapy, or waiting, with the need for strict surveillance. The present study reports the results of this latter attitude adopted in 23 cases out of 24 of limited resection in a group involving 119 partial laryngectomies (vertical or horizontal) consisting of: 57 cordectomies, 20 hemilaryngectomies, 42 supraglottal laryngectomies. Results of analysis show that there was no recurrence and patients were well with a 3 year follow-up in 19 cases of limited resection out of 24. Overall survival following limited resection was identical to that seen after satisfactory resection, but there was a marked difference with insufficient resection (X2 significant) Following partial laryngeal surgery involving a limit resection, it is felt to be legitimate to temporise as long as the patient can be seen regularly. Such an approach would not seem to modify the overall survival in these patients.

The case of a 23-year old transsexual male who developed a lethal lung disease 48 hr after a 1 l subcutaneous silicone fluid injection is reported. Histologic examination showed optically empty oil red O negative vacuoles in several specimens, and particularly in the lungs; refractile particles of silicium were also found. We identified the material as silicium, and evaluated its quantity in tissues by atomic absorption and spectrometric and toxicological analysis. Experimental studies and rare human accidents suggest that silicone fluid is transported by migrating phagocytes, thereby explaining lymph node, spleen, liver, adrenal and lung deposits. In our patient's report, we added gradual blood contamination to explain the progressive development of respiratory failure with the severity of the respiratory disorder linked to the massive dose injected. Massive silicone blood embolization could be excluded because of the interval between the injection and emergence of the first clinical signs.