Unnecessary orchiectomy due to atypical sarcoidosis manifesting as a unilateral scrotal mass: a case report and literature review.

Sarcoidosis is a disease characterised primarily by lung tissue involvement. Extrapulmonary involvement, particularly in the genitourinary tract, is extremely rare, particularly when it comes to primary disease detection in this location. The gold standard in establishing a definitive diagnosis of sarcoidosis is a combination of the clinical picture, the results of imaging methods, and histopathological examination from the biopsy taken (thus ruling out other causes of granulomatous inflammation). However, it is common for the biopsy to be infeasible or for the patient to refuse such an examination, resulting in the neglect of this critical verification. We introduce the case of a young 29-year-old man of Czech nationality who had been complaining for some time about non-specific pain above the pubic bone and in the lower abdomen, which was combined with a painless enlargement of the right half of the scrotum. Due to suspected malignancy, it was, after considering clinical, imaging, and laboratory findings, decided to perform a radical orchiectomy as a treatment option. The histological examination revealed that it was not cancer, but rather a rare genitourinary form of extrapulmonary sarcoidosis. In this case, radical resection had been, therefore, unnecessary. We also present a review of the literature on published extrapulmonary, genitourinary, and testicular sarcoidosis cases. All the above demonstrates the importance of considering a possible atypical sarcoidosis manifestation and histological confirmation before pursuing radical solutions.

A unique case of AH-dominant type nodular pulmonary amyloidosis presenting as a spontaneous pneumothorax: a case report and review of the literature.

Amyloidosis is a rare metabolic disorder primarily brought on by misfolding of an autologous protein, which causes its local or systemic deposition in an aberrant fibrillar form. It is quite rare for pulmonary tissue to be impacted by amyloidosis; of the three forms it can take when involving pulmonary tissue, nodular pulmonary amyloidosis is the most uncommon. Nodular pulmonary amyloidosis rarely induces clinical symptoms, and most often, it is discovered accidentally during an autopsy or via imaging techniques. Only one case of nodular pulmonary amyloidosis, which manifested as a spontaneous pneumothorax, was found in the literature. In terms of more precise subtyping, nodular amyloidosis is typically AL or mixed AL/AH type. No publications on AH-dominant type of nodular amyloidosis were found in the literature. We present a case of an 81 years-old male with nodular pulmonary AH-dominant type amyloidosis who presented with spontaneous pneumothorax. For a deeper understanding of the subject, this study also provides a review of the literature on cases with nodular pulmonary amyloidosis in relation to precise amyloid fibril subtyping. Since it is often a difficult process, accurate amyloid type identification is rarely accomplished. However, this information is very helpful for identifying the underlying disease process (if any) and outlining the subsequent diagnostic and treatment steps. Even so, it is crucial to be aware of this unit and make sure it is taken into consideration when making a differential diagnosis of pulmonary lesions.

Does dietary exposure to 17α-ethinylestradiol alter biomarkers related with endocrine disruption and oxidative stress in the adult triploid of Danio rerio?

This study was conducted to investigate a comprehensive effect of 17α-ethinylestradiol (EE2) in zebrafish (Danio rerio) with the emphasis on endocrine disruption, oxidative stress and detoxification processes at different levels. Adult male triploid zebrafish were exposed to EE2 administered in feed at two concentrations - 10 and 1000 µg/kg for six weeks. The estrogenic potential of EE2 was evaluated using an analysis of vitellogenin, gene expression focused on reproductive disorders and gonad histological examination. The alterations in antioxidant and detoxification status were assessed using analyses of enzyme activities and changes in transcriptional levels of selected genes. The most significant changes were observed especially in fish exposed to a high concentration of EE2 (i.e., 1000 µg/kg). Such high concentration caused extensive mortality (25 %) mainly in the second half of the experiment followed by a highly significant decrease in the length and body weight. Similarly, highly significant induction of vitellogenin level and vtg1 mRNA expression (about 43,000-fold compared to the control) as well as a significant downregulation of gonad aromatase expression (cyp19a1a) and histological changes in testicular tissue were confirmed in this group. In the group exposed to environmentally relevant concentration of EE2 (i.e., 10 µg/kg), no significant differences in vitellogenin were observed, although all fish were positive in the detection of vitellogenin compared to control, where only 40 % of individuals were positive. In addition, the high concentration of EE2 resulted in significant alterations in most monitored antioxidant and detoxifying enzymes with the exception of catalase, followed by strongly significant upregulation in mRNA expression of gsr, gpx1a, cat and cyp1a genes. Furthermore, a significant decrease in the glutathione reductase activity was recorded in fish exposed to 10 µg EE2/kg. To our knowledge, this is the first study which reports the effects of subchronic per oral exposure to EE2 in adult triploid zebrafish.

Extraskeletal myxoid chondrosarcoma: A study of 17 cases focusing on the diagnostic utility of INSM1 expression and presenting rare morphological variants associated with non-EWSR1::NR4A3 fusions.

Extraskeletal myxoid chondrosarcoma (EMC) is a rare sarcoma of uncertain lineage. Insulinoma-associated protein 1 (INSM1) has recently been described as a highly specific and sensitive immunohistochemical marker for EMC. The goal of this study was to evaluate the diagnostic significance of INSM1 immunohistochemistry in EMC. Furthermore, correlations between molecular and morphological findings were performed. Sixteen of 17 EMC cases were stained with the INSM1 antibody. Tumors with at least 5% INSM1-positive cells and any staining intensity were considered positive. Molecular testing was successfully performed in 12/17 cases. The immunohistochemical analysis detected 13 INSM1-positive (81%) and 3 INSM1-negative tumors (19%). The extent of the staining was classified as 1+ in 7 cases (44%), 2+ in 2 cases (13%), 3+ in 2 cases (13%) and 4+ in 2 cases (13%). Intensity of immunostaining was weak in 5 cases (31%), moderate in 2 cases (13%) and strong in 6 cases (38%). Molecular assays revealed 8 EWSR1::NR4A3 positive tumors (67%), 2 TAF15::NR4A3 positive tumors (17%), 1 TCF12::NR4A3 positive tumor (8%) and 1 NR4A3 positive tumor (8%) in which no other gene alteration was identified. Two of them, namely TCF12 positive and one TAF15 positive tumors, were highly cellular and partially associated with pseudopapillary architecture. Our study found that moderate/strong expression of INSM1 in more than 25% of tumor cells was present in only 31% of cases. Thus, the diagnostic utility of INSM1 is rather low. Two morphologically unique cases of non-EWSR1 rearranged EMC with an extremely rare pseudopapillary growth pattern are also reported.

Unique expression patterns of the embryonal stem cell marker SOX2 and hormone receptors suggest the existence of a subpopulation of epithelial stem/progenitor cells in porcine and bovine endometrium.

BACKGROUND: There are currently insufficient data on the population of endometrial epithelial stem/progenitor cells in farm animals. OBJECTIVES: With the aim of identifying a potential population of epithelial stem/progenitor cells in the porcine and bovine endometrium, this study immunohistochemically examined the expression patterns of the oestrogen and progesterone receptors, as well as that of the embryonal stem cell marker SOX2. METHODS: A total of 24 endometrial tissue samples obtained from cycling pigs (n = 12) and cows (n = 12) were included in our study. Each endometrium was divided into basal, middle and luminal portions. The percentage of marker-positive cells and the intensity of the immunoreaction in each portion of the endometrium were determined. RESULTS: Inverse expression patterns of SOX2 and progesterone receptors were found in both animal species throughout the oestrous cycle. Strong diffuse SOX2 expression was detected in the basal portions of the glands, while a significant decrease in positivity and a weak immunoreaction were found in the luminal two thirds of the glandular epithelium. Strong progesterone receptor expression was observed in at least 90% of glandular cells in the middle and luminal portions, whereas weak staining and significant decrease in positivity were detected in the basal portions of the glands. One oestrogen receptor expression pattern resembled that of progesterone receptors. CONCLUSION: The inverse expression patterns of SOX2 and hormone (especially progesterone) receptors suggest that endometrial epithelial stem/progenitor cells represent a subset of cells that reside in the basal portions of the endometrial glands in both the bovine and porcine endometrium.

Delayed ejaculation in men with depressive disorders.

Delayed ejaculation belongs to the group of sexual disorders in men. The causes of delayed ejaculation or anejaculation are not exactly known. It is assumed that it can be caused by psychogenic or organic influences or their combinations. One of the causes of delayed ejaculation may be elevated prolactin levels, which may be increased by psychosocial stress, pituitary disorders or also treatment with selective serotonin reuptake inhibitors in the treatment of depression. We tested a selected group of 50 men who were diagnosed with a depressive disorder and whose antidepressant treatment lasted for at least 24 weeks. These patients reported long-term delayed ejaculation or, in some cases, anejaculation as comorbidity. The results showed significant Spearman's correlation between elevated prolactin levels and intravaginal ejaculation latency values (R = 0.45), as well as between Beck's Depression-II inventory and intravaginal ejaculation latency and latency values (R = 0.48).

The effects of dietary exposure to Magnéli phase titanium suboxide and titanium dioxide on rainbow trout (Oncorhynchus mykiss).

Magnéli phase titanium suboxides (Magnéli TiOx) are promising, novel materials with superior properties compared to TiO2, they are substoichiometric titanium oxides with the chemical formula TinO2n-1 (where n ≥ 1). In this study, for the first time, subchronic effects of dietary intake of Magnéli TiOx were evaluated and compared with TiO2 particles of similar size, in concentrations 0.1% and 0.01% of feed. The experiment consisted of 38 d of an exposition period and 14 d of a depuration period. Minor effects on plasma biochemical profile and morphological parameters were recorded. A reduced count of leukocytes was found in the blood of both Magnéli TiOx and TiO2 exposed fish, suggesting immunotoxic effects. Erythrocytosis was specific for Magnéli TiOx. Indices of oxidative stress, namely increased lipid peroxidation in liver, increased activity of superoxide dismutase in liver, kidney and gills and glutathione S-transferase (GST) in gills, as well as decreased activity of ceruloplasmin and GST in liver were found predominantly in fish exposed to TiO2. Histopathological examination revealed increased lipid-like vacuolation in the liver, the presence of hyaline droplets in renal tubules and multiplication of mucous glands in the epidermis in both tested substances and intestine damage in TiO2 groups. Overall, in Magnéli TiOx exposed groups, fewer adverse effects compared to TiO2 expositions were recorded. Their wider practical implementation in place of TiO2 is therefore beneficial.

Foodborne fluoxetine impacts the immune response in rainbow trout (Oncorhynchus mykkis).

The aim of this study was to reveal the effects of foodborne fluoxetine on morphological and condition profile, hematological profile, biochemical and oxidative stress indices on juvenile rainbow trout. The study was performed according to OECD Guideline No. 215. Fluoxetine was incorporated into Biomar 921 pellets at a dose of 0.047 mg/kg (environmental concentration), 0.577 mg/kg and 6.7 mg/kg. There was statistically significant change in hematological profile, including an increasing trend in neutrophil/lymphocyte ratio and a decreasing trend in the number of lymphocytes. Measurements of oxidative stress indicated decreased activity of the detoxifying enzyme glutathione-S-transferase in the liver and kidney. However, the measurement of GR, GPx, CAT, SOD activity, and TBARS showed no changes. Histopathological examination revealed damage to the proximal tubules of caudal kidney in exposed groups. This study confirms that fluoxetine has a significant effect on immune response.

Effect of psychosocial trauma and stress on sexual dysfunction in women with endometriosis.

BACKGROUND: Endometrial tissue plays an important role in the regulation of female fertility and there is evidence that endometrial pathology (including endometriosis) is closely related to endocrine disorders. On the other hand, various neuroendocrine changes can be significantly affected by psychosocial stress. In connection with these findings, we tested the relationship between neuroendocrine changes, sexual dysfunction, psychosocial/traumatic stress, and dissociative symptoms in women with endometriosis. METHODS: A total of 65 patients with endometriosis were included in the study. Clinical examinations were focused on the biochemical analysis of neuroendocrine markers of endometriosis (cancer antigen 125 [CA 125] and cancer antigen 19-9 [CA 19-9]), estradiol, psychometric evaluation of sexual dysfunction, psychosocial/traumatic stress, and dissociative symptoms. RESULTS: The results showed significant Spearman correlations between the values of the revised range of sexual difficulties for sexual dysfunction (Revised Female Sexual Distress Scale), psychosocial/traumatic stress (Trauma Symptoms Checklist) (R = 0.31), and dissociative symptoms (Somatoform Dissociation Questionnaire) (R = 0.33). Positive correlations were also found between CA 125 and CA 19-9 (R = 0.63), and between CA 125 and the results of the values of the revised scale of sexual difficulties for sexual dysfunction (Revised Female Sexual Distress Scale) (R = 0.29). Also psychosocial/traumatic stress (Trauma Symptoms Checklist) significantly correlated with CA 125 (R = 0.38) and with CA 19-9 (R = 0.33). CONCLUSION: These results represent the first findings regarding the relationship of the neuroendocrine markers CA 125 and CA 19-9 and sexual dysfunction with trauma/stress-related symptoms and dissociative symptoms in women with endometriosis.

Premature ejaculation and stress.

Recent findings indicate that men with premature ejaculation report more frequent sexual problems associated with increased anxiety and interpersonal difficulties. Bearing this in mind, the neuroendocrine changes were examined in men with premature ejaculation and compared to other indicators of stressful experiences to see whether there can be any correlation which could indicate how these factors may contribute to the aetiology of premature ejaculation. Our study comprised 60 male outpatients diagnosed as having secondary premature ejaculation. Clinical examinations were focused on biochemical analysis of cortisol and psychometric scoring using a diagnostic tool for premature ejaculation, traumatic stress and somatoform dissociation. The control group consisted of a 60 healthy men. The results showed significant Spearman correlations of the Premature Ejaculation Diagnostic Tool score with Trauma Symptom Checklist score (R = .86), cortisol level (R = .47) and Somatoform Dissociation Questionnaire score (R = .61). In the control group, the results did not reach statistical significance. Spearman correlations of the Premature Ejaculation Diagnostic Tool score with Trauma symptoms checklist score was (R = .21), cortisol (R = .27) and with Somatoform dissociation questionnaire score (R = .25). These results represent the first reported findings documenting the relationship of traumatic stress indicators with the experience of secondary premature ejaculation and cortisol levels.

Effect of increased prolactin and psychosocial stress on erectile function.

Sexual dysfunctions in men are complex disorders that consist of organic and psychogenic components. The most common sexual dysfunction is erectile dysfunction. It is the inability to achieve or maintain an erection for satisfactory sexual performance. This disorder can be caused by high blood pressure, heart disease, vascular problems, psychological and hormonal factors such as problems with testosterone and prolactin levels. In this study, we tested the relationship between erectile dysfunction, hyperprolactinemia and psychosocial stress. Clinical examinations of 60 patients with erectile dysfunction, which also included psychosocial stress, focussed on patient history, comprehensive sexological examination, biochemical analyses of serum prolactin, total testosterone and thyroid-stimulating hormone with psychometric evaluation of erectile function and a checklist of trauma symptoms (TSC-40). The results show significant Spearman correlations of psychometric evaluation of erectile function with prolactin (R = .50) and results of the trauma checklist score (R = .55) and significant Spearman correlations between TSC-40 and prolactin (R = .52). This result indicates a significant relationship between erectile dysfunction, hyperprolactinemia and stress symptoms in men.

First Molecular Genetic Characterization of Skene's Gland Adenocarcinoma.

Primary urethral adenocarcinomas are very rare neoplasms accounting for <10% of all urethral carcinomas. Site of their origin is unclear, but they seem to arise from Skene's paraurethral glands, which is the female homologue of the male prostate. The aim of this article is to report the first case of Skene's gland adenocarcinoma in which a molecular genetic profiling was performed. The patient was a 73-year-old woman with a polypoid lesion sized 3 × 2 cm located at the interface between the bladder neck and the proximal urethra. Transurethral resection was performed and small tissue fragments with positive margins were obtained. Histology revealed an epithelial neoplasm consisting of cribriform structures located in the subepithelial connective tissue of the bladder wall and proximal urethra. The lesion showed positive immunohistochemical staining with prostate specific antigen, prostatic acid phosphatase, NKX3.1, and alpha-methylacyl-CoA racemase. Using the Illumina TruSight Tumor 170 next-generation sequencing assay, a mutation and loss of heterozygosity of the phosphatase and tensin homologue (PTEN) gene was detected. No fusion in any of the examined genes was found using this assay as well as FusionPlex Solid Tumor Kit and FusionPlex Sarcoma kit assays from ArcherDX. Given the rarity of Skene's gland adenocarcinoma, it is uncertain whether the same grading and prognostic criteria that are currently used for prostatic cancer apply here as well. It is also unclear what treatment strategy should be applied, but according to the available literature, it seems that local excision or wide surgical resection could represent sufficient therapeutic modalities.

Comparative immunohistochemical study of deep infiltrating endometriosis, lymph node endometriosis and atypical ovarian endometriosis including description of a perineural invasion.

AIM: Endometriosis is an inflammatory condition that shares a number of similarities with malignant diseases, such as an abnormal morphology, migration along the nerve bundles and metastatic spread to lymph nodes and distant organs. Endometriotic lesions are associated with oestrogen and progesterone imbalance which seems to play a key role in the pathogenesis of endometriosis. The aim of this study was to compare the status of both oestrogen and progesterone receptors in tissue of deep infiltrating endometriosis, lymph node endometriosis and atypical ovarian endometriosis using immunohistochemical methods, as well as to investigate the relationship between endometriosis and protein p53. METHODS: A total of 40 cases with deep infiltrating endometriosis were included in our study. Based on histopathological analysis of resected specimens, the cases were divided into 2 groups: group 1 - lymph node endometriosis (cases with lymph node involvement; n=12) and group 2 - deep infiltrating endometriosis (cases without lymph node involvement; n=28). As a control group, eutopic endometrium of adenomyosis- and endometriosis-free women were used (n=16). Five cases of atypical ovarian endometriosis as well as descriptions of the nerve involvement in endometriosis were also included. Immunohistochemical staining with a total of 4 markers was performed - oestrogen and progesterone receptors (ER, PR), p53 and Ki-67 (proliferation index). RESULTS: The immunophenotype of the cases in groups 1 and 2 and in the control group was virtually identical in the proliferative phase - strong nuclear ER and PR expression in more than 90% of endometrial glandular and stromal cells. In the early and mid secretory phase, ER expression only slightly decreased (80%) in endometrial glandular cells in group 2 and the control group, whereas in the late secretory phase, significant decrease of ER expression only in the control group was observed (15-50%; P<0.001). In group 2 and the control group, significant decrease of PR expression only in endometrial glandular cells was observed in the mid and late secretory phase (less than 15%; P<0.001). Differences in receptor content were found only in isolated cases in group 2. In group 1, no secretory changes were found. In all three groups, sporadic and weak nuclear p53 expression in less than 3% in both endometrial glandular and stromal cells was detected (regardless of the phase of the menstrual cycle). In atypical ovarian endometriosis, higher and strong p53 expression (on average 26%) and decrease in ER (on average 56%) and PR (less than 1%) expression was observed; compared to the control group and groups 1 and 2, the differences for all 3 markers were highly significant (P<0.001). In all groups, the proliferation index (Ki-67) reached the highest values in the proliferation phase and decreased during the cycle. However, in endometriotic tissue, it was widely variable in the individual phases of the cycle. Perineural spread of endometriosis with significant neural hypertrophy, hyperplasia and involvement of the ganglia of the autonomic nervous system was detected in 5 cases (12.5%). Conlusion. From a histological and immunohistochemical point of view, deep infiltrating endometriosis and lymph node endometriosis appear to represent the same entity. For the first time, a simple immunohistochemical panel with antibodies against ER, PR and p53 useful in diagnosing atypical endometriosis has been described. The marked endometriosis-associated neural changes (endometriotic neuropathy) could be one of the causes of impaired function of the affected organs after debulking surgery with macroscopic negative resection margins as well as pain symptomatology in macroscopic inapparent endometriotic lesions.

Psychosocial stress, somatoform dissociative symptoms and free testosterone in premature ejaculation.

One of the most common sexual dysfunctional diseases in adult males is premature ejaculation. So far, there is no evidence of how premature ejaculation is associated with psychosocial stress. We tested the relationship between neuroendocrine changes in patients with premature ejaculation and indicators of stress experience as a new psychosomatic hypothesis where psychosocial stress may significantly contribute to the aetiology of premature ejaculation. A total of 55 patients with premature ejaculation were included in the study. The control group consisted of 55 healthy men. The diagnosis of premature ejaculation was confirmed by a sexology examination, a history of patients and the values of the premature ejaculation diagnostic tool questionnaire. Comprehensive biochemical serum analysis was focused on the values of total testosterone, free testosterone, luteinising hormone, thyroid-stimulating hormone, dehydroepiandrosterone sulphate, sex hormone-binding globulin and a premature ejaculation diagnostic tool score with trauma symptom checklist and somatoform dissociation questionnaire. The results show significant Spearman correlations of trauma symptom checklist with the premature ejaculation diagnostic tool score (R = 0.84) and free testosterone (R = 0.62) and somatoform dissociation questionnaire with the premature ejaculation diagnostic tool score (R = 0.53) and free testosterone (R = 0.57). Spearman correlations of trauma symptom checklist with somatoform dissociation questionnaire show significant correlation (R = 0.54).

Novel EIF5A-USP6 Gene Fusion in Nodular Fasciitis Associated With Unusual Pathologic Features: A Report of a Case and Review of the Literature.

Nodular fasciitis (NF) is a benign self-limiting soft tissue lesion that has long been considered a reactive process. Recently, however, the USP6 gene rearrangement has been discovered, and the neoplastic nature of this tumor was suggested. Since then, many fusion partners of the USP6 gene have been reported, with the MYH9 gene as the most common. In this article, we describe a case of NF with a novel EIF5A-USP6 gene fusion associated with unusual pathological features. A 41-year-old healthy woman with a painful, rapidly growing subcutaneous mass on the left forearm with a size of 0.8 cm is presented. A soft tissue fragment measuring 1 cm was surgically excised. Owing to positive surgical margins, re-excision was performed, yielding another 2-cm fragment. The lesion was extensively histologically investigated. Immunohistochemical and molecular-genetic analysis, namely fluorescence in situ hybridization, next-generation sequencing, and reverse transcriptase-polymerase chain reaction, were also performed. Histology revealed a dermally located, mitotically active myofibroblastic proliferation with myxoid areas that ulcerated the overlying epidermis. One atypical mitotic figure was also found. The lesion showed positive immunohistochemical staining with smooth muscle actin, whereas S100 protein and CD34 stains were negative. Using fluorescence in situ hybridization, the USP6 gene rearrangement was detected and subsequent analysis using the Archer fusionPlex Sarcoma kit revealed a novel EIF5A-USP6 gene fusion. In the appropriate clinicopathological context, the detection of USP6 gene rearrangement is extremely useful when diagnosing NF, significantly reducing the risk of misdiagnosis and inappropriate overtreatment.

Rectal perforation caused by deep infiltrating endometriosis in non-pregnant woman: Case report and short review of the literature.

AIM: The aim of this paper is to describe an unique case of deep infiltrating endometriosis of the rectum in non-pregnant woman with unusual clinical and pathological presentation resulting in spontaneous perforation. MATERIALS AND METHODS: A female (20 years of age) with a two year history of chronic recurrent abdominal pain of unknown etiology treated by a psychiatrist underwent diagnostic laparoscopy which revealed many peritoneal implants of endometriosis involving the right ovarian fossa, the vesico-uterine pouch and sacrouterine ligament; the bowel wall showed no structural abnormalities. Peritonectomy of the broad and uterosacral ligaments was used and eight days after the operation, the patient developed crampy abdominal pain and enterorrhagia necessitating laparoscopic revision; pelvic haematoma and rectosigmoiditis were found. Over the next three days, perforation of the rectum resulted in the presence of fecal material in the surgical drain. RESULTS: Lower rectal resection with ileostomy was performed. Microscopic examination revealed discrete small endometriotic lesions in submucosa, muscular layer and serosa of the rectum associated with perforation. DISCUSSION: Laparoscopy and laparotomy may be insufficient in the case of an inactive endometriosis. Definitive diagnosis is thus reached only by the histological examination. The pathophysiology of the bowel perforation secondary to endometriosis is not entirely clear. CONCLUSION: The presented case confirms the importance of interdisciplinary cooperation between surgeons, gynaecologists, and pathologists. We also want to emphasize the need for extensive pathological examination of the resected specimens which is essential for a proper diagnosis. KEY WORDS: Endometriosis, Rectum, Spontaneous perforation.

Endometriosis with an aberrant immunophenotype: Challenging differential diagnosis of glandular lesions in the pelvic lymph nodes.

CASE REPORT: We describe an unusual case of pelvic lymph node endometriosis with an aberrant immunophenotype mimicking metastasis of adenocarcinoma. A 37-year-old patient with a history of invasive cervical adenocarcinoma stage pT1a2 is presented. Due to insufficient loop electrosurgical excision procedure (LEEP) conization, total laparoscopic hysterectomy with pelvic lymphadenectomy was indicated. Intraoperatively, the diagnosis of deep infiltrating endometriosis of parametrial ligament and vesicouterine pouch, endometrioma of the left ovary and Allen Master's syndrome was suspected; the patient had no history or clinical symptoms of endometriosis. A PubMed search of similar cases was followed by a comparison to this case and discussion of the differential diagnosis of glandular lesions in the pelvic lymph nodes is reported. RESULTS: Histological investigation showed no residual neoplasia; the diagnosis of endometriosis was confirmed. An interesting microscopic finding was represented by a solitary glandular lesion in one pelvic lymph node. Using immunohistochemistry, it was demonstrated that there was a complete loss of oestrogen and progesterone receptor expression (unlike parametrial ligament endometriosis). The diagnosis of endometriosis was based on the presence of endometrial stroma; malignancy was excluded by bland cytomorphologic features and results of immunohistochemical examination. CONCLUSIONS: This type of aberrant of the endometriotic gland immunophenotype has never been presented in the scientific literature before. This finding plays a significant role from the pathology standpoint and, perhaps more importantly, from the clinical standpoint. An asymptomatic patient with a correct diagnosis of lymph node endometriosis did not undergo excessive treatment for false positive diagnosis of metastatic cervical adenocarcinoma.

MiR-21, miR-34a, miR-198 and miR-217 as diagnostic and prognostic biomarkers for chronic pancreatitis and pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma is an aggressive malignancy with late presentation, metastatic potential and very poor prognosis. Therefore, there is an urgent need for novel diagnostic and prognostic biomarkers. MicroRNAs are small non-coding RNAs that post-transcriptionally regulate gene expression. Altered expression of microRNAs has been reported in wide range of malignancies, including pancreatic ductal adenocarcinoma. The aim of this study was to analyze the expression of selected microRNAs in normal pancreas, chronic pancreatitis and pancreatic ductal adenocarcinoma tissues and evaluate their diagnostic and prognostic potential. FINDINGS: Using quantitative real-time PCR, expression levels of 4 microRNAs were examined in 74 tumor tissues, 18 tissues of chronic pancreatitis and 9 adjacent normal tissues and correlated with clinicopathological features of patients. Expression levels of miR-21, miR-34a and miR-198 were significantly higher, whereas levels of miR-217 were significantly lower in pancreatic ductal adenocarcinomas compared to healthy tissues and tissues of chronic pancreatitis. Moreover, increased expression of miR-21 and miR-198 was significantly associated with shorter disease free survival and overall survival. CONCLUSIONS: Our data suggest that altered expression of examined microRNAs is related to neoplastic transformation and progression of the disease and these microRNAs could serve as diagnostic and prognostic biomarkers for pancreatic ductal adenocarcinoma. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1373952531543898.

Anterior gradient 2 and mucin 4 expression mirrors tumor cell differentiation in pancreatic adenocarcinomas, but aberrant anterior gradient 2 expression predicts worse patient outcome in poorly differentiated tumors.

OBJECTIVES: This study aimed to determine anterior gradient 2 (AGR2) expression in biopsies from pancreatic ductal adenocarcinomas (PDACs) and to evaluate AGR2 as a potential independent prognostic factor. METHODS: Tissue sample sections from a cohort of 135 consecutive surgically resectable PDACs were subjected to semiquantitative immunohistochemical analysis of AGR2 and mucin 4 (MUC4) expression. RESULTS: Anterior gradient 2 was over-expressed in PDAC compared with normal ductal cells. Since tumor lesions of PDAC are heterogeneous and constitute structures with various differentiation states, expression of both AGR2 and MUC4 was evaluated in each separate component. Expression levels of both proteins reflected the degree of tumor differentiation. Generally, well differentiated regions of tumor lesions expressed high levels of both proteins, moderately differentiated regions showed less AGR2 and MUC4, and poorly differentiated structures showed only weak positivity or were entirely negative. Of particular interest were occasional cases of strong AGR2 expression in high-grade tumors, where elevated protein levels were associated with shorter patient survival. CONCLUSIONS: Anterior gradient 2 and MUC4 reflect the level of differentiation of PDACs. However, in less differentiated tumors, aberrantly elevated AGR2 expression predicts poor patient outcome.

Clinicopathological correlations of nestin expression in surgically resectable pancreatic cancer including an analysis of perineural invasion.

BACKGROUND AND AIMS: Nestin is considered to be a marker of stem/progenitor cells in different tissues. Nestin expression was also described in various tumors. In pancreatic ductal adenocarcinoma (PDAC), its role in cancer cell migration, invasion, and metastases has been suggested. The study aimed at examining the expression of nestin in PDAC, and to evaluate its clinicopathological correlations. METHODS: The expression of nestin was immunohistochemically examined in 117 PDAC resection specimens, analyzed, and correlated with clinico-pathological parameters including perineural invasion (PNI). Analysis of nestin expression in nerve fibers in tissues of chronic pancreatitis (CP) was added. RESULTS: Immunohistochemical analysis of nestin expression showed 79 nestin negative (67.5 %) and 38 nestin positive (32.5 %) PDACs. No significant correlations of nestin expression in tumor cells with the analyzed clinicopathological parameters were demonstrated. Tumor grade (p<0.001) and nodal status (p=0.009) proved to represent independent prognostic factors. PNI was identified in 94 PDAC (80.3 %), and did not correlate with nestin expression. Nestin immunostaining was displayed in nerve fibers of both CP and PDAC tissues. CONCLUSION: An intimate link of nestin to a biological process of pancreatic cancer was confirmed. The expression of nestin did not prove to be a valuable prognostic factor and an immunohistochemical assessment of nestin expression is not superior to conventional prognostic factors in PDAC. A correlation between nestin expression in tumor cells and PNI was not confirmed and expression of nestin in nerve fibers of both PDAC and CP tissues seems to reflect the process of neural remodeling responsible for pancreatic neuropathy.