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Introduction: Perineal schwannomas (PS) are very rare benign tumors with few cases reported in literature and none of these reports erectile dysfunction among clinical presentations. Case description: We report a case of PS with unusual clinical presentation showing erectile dysfunction associated with perineal pain and discomfort during defecation, and the postoperative residual pain and erectile dysfunction treatment. Conclusions: On the basis of a literature review of all cases reported and on our case reported, we have delineated a clinical, diagnostic, and therapeutic profile of PS, summarized in a useful table.

Translationally controlled tumor protein is a multifaceted protein involved in several physiological and biological functions. Its expression in normal kidney and in renal carcinomas, once corroborated by functional data, may add elements to elucidate renal physiology and carcinogenesis. In this study, translationally controlled tumor protein expression was evaluated by quantitative real time polymerase chain reaction and western blotting, and its localization was examined by immunohistochemistry on 84 nephrectomies for cancer. In normal kidney protein expression was found in the cytoplasm of proximal and distal tubular cells, in cells of the thick segment of the loop of Henle, and in urothelial cells of the pelvis. It was also detectable in cells of renal carcinoma with different pattern of localization (membranous and cytoplasmic) depending on tumor histotype. Our data may suggest an involvement of translationally controlled tumor protein in normal physiology and carcinogenesis. However, functionalin vitroandin vivostudies are needed to verify this hypothesis.

Idiopathic hypertrophic cranial pachymeningitis (IHCP) is a rare, poorly understood, inflammatory disease, usually involving the dura mater of skull base, tentorium, and falx, and presenting with headache, progressive cranial nerve palsies, and cerebellar dysfunction. In four patients, the diagnosis of IHCP has been made on the basis of extensive clinical, and radiological investigation, and confirmed by dural biopsy in three patients. The clinical follow-up ranges from 24 to 120 months. At diagnosis, all the patients complained of severe, progressively increasing headache, two had simple or complex partial seizures, but none had cranial nerve palsies. Two patients had electrophysiological evidence of axonal peripheral neuropathy, biopsy-proved in one of them. In all the patients, MRI showed linear or focal thickening of the dura mater of the tentorium and/or of the convexity, sparing the skull base. In one patient, MRI findings resembled chronic subdural hematoma. Dural biopsy demonstrated fibrosis and prominent CD4+ T-cells inflammatory infiltrate. Pachymeningitis was highly responsive to steroid therapy, as was the peripheral neuropathy. In three patients, temporary steroids withdrawal led to dramatic clinical worsening including status epilepticus in one. In the patients here reported, absence of cranial nerve impairment, seizures, MRI findings resembling chronic subdural hematoma, and association with polineuropathy were unusual findings of IHCP. Moreover, the type of inflammatory infiltrate, lacking in previous reported cases, suggests a probable pathogenetic role for cell-mediated immunity of unknown origin.

AimsAn external positive control section is included in each immunohistochemical analysis as a well recognised and validated technique for standardising results. The method is time-consuming and expensive. On the contrary, internal controls are warranted and inexpensive, but their use is only feasible in selected diagnoses. The aim of this work is to show how the method of the authors allows improving the interpretation and cuts costs in the immunohistochemical analysis of bone marrow specimens.MethodsA paraffin-embedded tonsil tissue cylinder was sampled from a donor block using an automated sampler and included as an ‘internal control’ together with a bone marrow biopsy in a recipient block, avoiding the use of external tonsil tissue control. To validate this technique, the authors compared the quality of immunohistochemistry, the workload and costs with routine external control in 50 consecutive bone marrow biopsies.ResultsProcessing simultaneously the sample and the tissue control in the same block, 60 external positive control tests were spared. Only a few minutes were taken for the preparation of the recipient blocks, and no particular technical skill was required. Considering that the volume of antibodies used for the analysis of each sample was not increased, a considerable amount of the disposable material was saved. The workload of technicians was decreased and some potential technical bias was avoided. The time required for pathologists to interpret the slides was also reduced.ConclusionsIn conclusion, this seems to be a feasible, cost-cutting and quality-improving technique, not limited to haematopathology but potentially extensible to other fields of pathology.

Human milk is a source of bioactive substances regulating the development and activity of the newborn immune system. Human milk has been found to contain a number of cytokines, including interleukins, growth factors, and colony stimulating factors. In the present study, we assessed 10 specimens of human milk for the presence of macrophage migration inhibitory factor (MIF), a cytokine recently described in several human reproductive organs and tissues. Using biochemical as well as immunologic techniques, we showed that MIF is abundantly present in human milk, mostly distributed in the lipid layer and in the aqueous phase. Fractionation of the lipid layer showed that MIF is highly concentrated inside milk fat globules. In view of its proinflammatory features, we speculate that milk MIF may protect the newborn against infection and play a role in preserving the functionality of the lactating mammary gland. Furthermore, the localization of MIF in lipid globules suggests a possible strategy for the protection of milk cytokines from the gastric barrier.

Amphicrine carcinoma is a peculiar tumor in which the cells have both exocrine and neuroendocrine differentiation, with mucus and neuroendocrine granules within the cytoplasm. In the 2010 WHO classification of tumors of the digestive tract, they have been included in the intermediate-grade malignant category of mixed adenoneuroendocrine carcinomas (MANECs). These tumors are extremely rare in the gastrointestinal tract. Four cases have been reported in the stomach, three in the pancreas, and one in the liver. To the best of our knowledge, this report describes the first case of amphicrine carcinoma in the ampullary region.

Acute esophageal necrosis, commonly referred to as ‘black esophagusʼ, is a rare clinical entity arising from a combination of ischemic insult, corrosive injury and decreased function of mucosal barrier systems and reparative mechanisms present in debilitating diseases. We describe the case of an 18-year-old man affected by Down syndrome, presenting with a streptococcus β-hemolytic group A infection of the upper airways. Although the patient was intensively treated with antibiotics, he developed a streptococcal toxic shock-like syndrome and died 5 days after admission. At autopsy, circumferential black discoloration of the esophageal mucosa that extended along the entire esophagus and ended abruptly at the esophageal-gastric junction was found. Neither ulceration nor esophageal perforation were present. Black esophagus is well known to the gastroenterology community, whereas it has been described only twice in the pathology literature. To the best of our knowledge, this is the first case ever reported complicating a streptococcal infection.

Macrophage migration inhibitory factor (MIF) was discovered as an activated T-lymphocyte-derived protein that inhibits the random migration of macrophages in vitro. Subsequently, knowledge of the physiological actions of MIF was extended to include its role as a proinflammatory cytokine that affects several functions of macrophages and lymphocytes. Previous reports have suggested an involvement of MIF in reproduction. However, no data are currently available on the presence of this cytokine in the human endometrium. In this study, the expression and tissue localization of MIF was evaluated in specimens of cycling endometrium, first trimester placenta bed biopsy, and isolated endometrial glands by Western blot analysis, immunohistochemistry, ELISA, and reverse transcription-polymerase chain reaction. The results demonstrated that MIF is expressed in human endometrium across the menstrual cycle and in early pregnancy. Immunohistochemical localization identified the protein in glandular epithelium, in stromal and predecidualized stromal cells of cycling endometrium, as well as in the decidua of first-trimester placenta. The proinflammatory features and specific actions of MIF on lymphoid cells suggest its potential involvement in several aspects of endometrial physiology.

Background: Pneumococcal meningitis (PM) is a life-threatening disease with a high case-fatality rate and elevated risk for serious neurological sequelae. In this study, we investigated the contribution of three major virulence factors of Streptococcus pneumoniae, the capsule, pneumococcal surface protein A (PspA) and C (PspC), to the pathogenesis of experimental PM. Methods: Mice were challenged by the intracranial route with the serotype 4 TIGR4 strain (wt) and three isogenic mutants devoid of PspA, PspC, and the capsule. Survival, bacterial counts, and brain histology were carried out. To study the interaction between S. pneumoniae mutants and microglia, phagocytosis and survival experiments were performed using the BV2 mouse microglial cell line. Results: Virulence of the PspC mutant was comparable to that of TIGR4. In contrast, survival of animals challenged with the PspA mutant was significantly increased compared with the wt, and the mutant was also impaired at replicating in the brain and blood of infected mice. Brain histology indicated that all strains, except for the unencapsulated mutant, caused PM. Analysis of inflammation and damage in the brain of mice infected with TIGR4 or its unencapsulated mutant demonstrated that the rough strain was unable to induce inflammation and neuronal injury, even at high challenge doses. Results with BV2 cells showed no differences in phagocytic uptake between wt and mutants. In survival assays, however, the PspA mutant showed significantly reduced survival in microglia compared with the wt. Conclusions: PspA contributed to PM pathogenesis possibly by interacting with microglia at early infection stages, while PspC had limited importance in the disease. The rough mutant did not cause brain inflammation, neuronal damage or mouse death, strengthening the key role of the capsule in PM.

Glomus tumors are rare, mesenchymal neoplasms of adulthood, which occur in both the sexes with equal frequency. Most of these tumors are benign, but some cases with atypical/malignant behavior have been reported. They most often occur in the extremities, typically in the subungual region of the fingers, and rarely involve the internal organs. We report the case of a 63-year-old man who presented with hematuria. The cystoscopy showed a polypoid lesion of the anterior wall of the bladder, which was diagnosed on biopsy as a benign glomus tumor. To the best of our knowledge, this is the first case of benign glomus tumor of the bladder described in the literature. This report widens the spectrum of the differential diagnoses of bladder neoplasms.

Neuropathological study of a 3 1/2 year old girl with familial Leigh syndrome who also harboured a rare ATPase gene mutation disclosed extensive and unusual lesions in the cerebral cortex, despite a typical histological pattern. Early lesions in the periacqueductal grey matter of the brainstem, characterised by capillary congestion and initial regressive neuronal changes, were also observed, along with TUNEL reactive neuronal cells showing morphological signs typical of apoptosis in cortical areas with neuronal cell loss. The finding of lesions in atypical brain areas and for the first time, very early regressive neuronal phenomena, suggest that early changes in crucial brain areas may have been a cause of death. The abundance of TUNEL positive nuclei in cortical areas in the present case suggests that the apoptosis may be involved in the mechanism of neuronal death in Leigh syndrome.

Pancreatic islet transplantation is a promising cell-based therapy for type 1 diabetes (insulin-dependent diabetes mellitus), a disease triggered by the immune response against autoantigens of beta-cells. However, the recurrence of immune response after transplantation and the diabetogenic and growth-stunting side effects of immunosuppressants are major challenges to the application of islet transplantation. Mesenchymal stem cells (MSCs) have recently been reported to modulate the immune response in allogeneic transplantation.The ability of MSCs, either syngeneic or allogeneic to recipients, to prevent acute rejection and improve glycemic control was investigated in rats with diabetes given a marginal mass of pancreatic islets through the portal vein.Reduced glucose levels and low-grade rejections were observed up to 15 days after transplantation upon triple-dose administration of MSCs, indicating that MSCs prolong graft function by preventing acute rejection. The efficacy of MSCs was associated with a reduction of pro-inflammatory cytokines and was independent of the administration route. Efficacy was similar for MSCs whether syngeneic or allogeneic to recipients and comparable to that of immunosuppressive therapy.The results show that MSCs modulate the immune response through a down-regulation of pro-inflammatory cytokines, suggesting that MSCs may prevent acute rejection and improve graft function in portal vein pancreatic islet transplantation.

The polysaccharide capsule is a major virulence factor of Streptococcus pneumoniae as it confers resistance to phagocytosis. The encapsulated serotype 4 TIGR4 strain was shown to be efficiently phagocytosed by the mouse microglial cell line BV2, whereas the type 3 HB565 strain resisted phagocytosis. Comparing survival after uptake of TIGR4 or its unencapsulated derivative FP23 in gentamicin protection and phagolysosome maturation assays, it was shown that TIGR4 was protected from intracellular killing. Pneumococcal capsular genes were up-regulated in intracellular TIGR4 bacteria recovered from microglial cells. Actual presence of bacteria inside BV2 cells was confirmed by transmission electron microscopy (TEM) for both TIGR4 and FP23 strains, but typical phagosomes/phagolysosomes were detected only in cells infected with the unencapsulated strain. In a mouse model of meningitis based on intracranic inoculation of pneumococci, TIGR4 caused lethal meningitis with an LD(50) of 2 × 10² CFU, whereas the LD(50) for the unencapsulated FP23 was greater than 10⁷ CFU. Phagocytosis of TIGR4 by microglia was also demonstrated by TEM and immunohistochemistry on brain samples from infected mice. The results indicate that encapsulation does not protect the TIGR4 strain from phagocytosis by microglia, while it affords resistance to intracellular killing.

A total of 55 formalin-fixed and paraffin-embedded specimens of normal, inflamed and neoplastic uterine cervix have been studied in order to correlate the epithelial changes with the expression of alpha-smooth-muscle actin in stromal cells. This actin isoform is typical of smooth-muscle cells, but appears also temporarily in fibroblasts during wound healing and permanently during fibrocontractive diseases and stromal reaction to epithelial tumors. While positive stromal cells were absent in normal and inflamed cervix, they accumulated in relation to neoplastic tissues. The number of alpha-smooth-muscle actin positive cells and the intensity of stain were related to the increasing grading of cervical intra-epithelial neoplasia. Our results suggest that alpha-smooth-muscle actin is a marker of stromal-cell reaction to the development of neoplastic lesions. The evaluation of alpha-smooth-muscle actin in stromal cells of the uterine cervix may be a useful adjunct to diagnostic criteria of cervical intra-epithelial neoplasia and may help understanding of the mechanisms of mesenchymal-epithelial interactions during neoplasia.

Hemangiopericytomas are rare vascular tumors arising from Zimmerman's pericytes, which ubiquitously surround blood capillaries and post-capillary venules. The orbit is an uncommon site; mostly isolated cases or small series are reported; the authors' series includes five cases (two males and three females, mean age 40 years, range 21-79 years). The tumors were rarely painful and were usually noticed because of a rapid growth; in three cases there was evidence of recurrence after surgical excision. Up to today the follow-up time ranges between one and 22 years. Histopathologic and immunohistochemical data are also reported with particular attention to the differential diagnosis. The authors also try to correlate the anatomopathological features with the clinical behavior.

The diagnostic accuracy of orbital rhabdomyosarcoma (RMS) in childhood may be increased by the use of immunohistochemical methods. In this study, 19 cases of rhabdomyosarcoma were immunostained and the immunohistochemical results were compared with anatomo-clinical data. Desmin and sarcomericactin seem to be the more useful markers for the diagnosis of RMS. The other markers tested (myoglobin, polyclonal actin, vimentin and enolase) were unreliable because of several reasons. Finally, immunohistochemical analysis supplies data regarding the degree of tumor differentiation and may be applied to monitor radio- and chemotherapy.

We have established two murine cell lines derived from Small Cell Lung Carcinomas (SCLCs) developed by HPV-E6/E7 transgenic mice. These cells named PPAP-9 and PPAP-10 were isolated from mice bearing tumors, 9 and 10 months old, respectively. The cells, 5 microm in diameter, express HPV oncoproteins and sustain tumor formation after subcutaneous injection in syngenic mice. A detailed analysis indicated the epithelial origin and the neuroendocrine differentiation of these cells. We showed by confocal immunofluorescence the expression of the epithelial marker cytokeratin 5, whose gene promoter was used to direct the expression of HPV E6/E. Cells express several neuroendocrine markers such as CGRP, MAP-2, Ash1, CgrA, Scg2. The neuroendocrine differentiation of these cells was further confirmed by electron microscopy demonstrating neuropeptides secreting granules in their cytoplasm. Furthermore, in agreement with the altered expression observed in the majority of human SCLC we showed in these cells the absence of both p53 and pRB and a dramatic reduction in the expression of Caveolin-1.

Human Papillomavirus type 16 (HPV-16) is the cause of both benign lesions and ano-genital cancers. In HPV-associated cancers the transforming properties of the expressed viral E6 and E7 proteins have been revealed by a number of different assays. We have generated transgenic mice expressing HPV-16 E6/E7 genes under the control of the murine keratin 5 gene promoter, which should confer cell-type specific expression in the basal cells of squamous stratified epithelia. Transgenic mice developed thymic hyperplasia and lung neoplasia with 100% frequency, the thymus showing a size increase at 2 months and reaching the maximum dimension at 6 months, when lung carcinomas appeared. After this time the size of hyperplastic thymi decreased, while malignant formations invaded the mediastinal area. Hepatic metastasis could be also observed in some of the animals at the autopsy and death invariably occurred around 10-11 months of age.

It has been proposed that oxidative stress develops in tumors, with important consequences for growth and progression. To investigate this hypothesis, we measured low m.w. thiols, disulfides, protein-mixed disulfides and a pool of major anti-oxidant enzymes in renal-cortex as well as renal-cell carcinoma (RCC) specimens at stages I-II and III. Our data showed (i) a significant increase in the levels of total intracellular glutathione at both tumor stages (levels were 2.6-2.8 fold higher than those in the normal renal cortex), (if) a marked lowering of the GSH/GSSG ratio in stage I-II accompanied by a significant decrease of many GSH-dependent enzymes (i.e., GPX, GST, GGT, GR) and (iii) unchanged GSH/GSSG ratio and GSH-dependent enzyme activity in stage III with respect to normal renal cortex. These results indicate that relevant variations exist in the glutathione anti-oxidant system in the different stages of RCC and support the hypothesis that oxidative stress plays an important role in RCC growth and progression.

BACKGROUND Macrophage migration inhibitory factor (MIF) is a ubiquitary cytokine whose expression has been investigated in tumors, showing a correlation between tumor aggressiveness and production of this protein by neoplastic cells. The aim of our study was to correlate MIF expression with tumor grade (Gleason scoring system) and histopathological changes after combined endocrine treatment (CET) of prostate adenocarcinoma. METHODS We analyzed MIF immunoreactivity in 124 paired needle biopsies and radical prostatectomy specimens from 62 prostate cancer patients, of which 20 had been treated with CET. RESULTS In untreated prostates, MIF expression significantly correlated with tumor grading, being stronger in low-grade than in high-grade adenocarcinoma. In treated prostates, histopathological changes also correlated with MIF immunoreactivity, but not in a significant manner. CONCLUSIONS The results of the current study demonstrated that with histological dedifferentiation, prostate adenocarcinoma cells show a reduced MIF expression. This finding may be the consequence of a reduced MIF synthesis or the result of an enhanced and altered secretion by tumor cells into the surrounding stroma. The consequent abnormal interaction between MIF and environmental factors might influence tumor growth and diffusion. On the other hand, the minor but not significantly reduced MIF expression by tumor cells after CET seems to exclude a hormonal regulation of MIF secretion. Prostate 45:51–57, 2000. © 2000 Wiley-Liss, Inc.

We report neuropathological findings in a 22-year-old man affected with neuronal intranuclear inclusion disease. The inclusions affected to different extents the various structures of the central nervous system, being more numerous in cerebral cortex, inferior olives, hypoglossal and oculomotor nuclei. They ultrastructurally differed from Marinesco bodies. In the neurons of the substantia nigra, we occasionally observed intranuclear inclusions resembling the so-called rodlets of Roncoroni. We did not observe inclusions in the extraneuronal tissues. There was no apparent correlation between frequency of the inclusions and neuronal loss. Intranuclear inclusions were found in many morphologically normal neurons. We suggest that the intranuclear inclusions are the marker of a distinctive disorder, even though their role in neuronal degeneration remains to be clarified.

We describe an Italian male patient, deceased at 29 years of age, affected with a syndrome characterized by childhood-onset seizures, mental disorders, motor dysfunction and bilateral palatal myoclonus. Skeletal X-ray examination showed diffuse osteopenia of the tubular bones, and cyst-like lesions in the carpal, metacarpal and tarsal bones bilaterally and in the proximal end of the right femur. Skin biopsy showed subcutaneous and adipose tissue containing membranocystic structures. Cerebral MR and CT scans showed fronto-temporal atrophy, altered signal of the white matter and mineralization of the caudate and dentate nuclei. These findings strongly recall polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy, but in the present case, bone alterations were not prominent; moreover, palatal myoclonus has never previously been described in this syndrome.

Immunofluorescence and immunoelectron microscopy indicated that the antibody raised against the nuclear antigen Ki-67 of mammalian cells recognized antigenic determinants of early Drosophila embryos, localized on the outside of the nuclear envelope. Hence, the nuclear envelope of Drosophila appears to share a similar epitope with the chromosome scaffold of mitotic mammalian cells. With the progression of mitosis the antigen persisted around the mitotic spindle region and was also found in the pole regions at metaphase and anaphase. The antibody also stained the equatorial regions of the spindles from anaphase to late telophase. The antibody may therefore be used as a biochemical marker of the nuclear envelope for studying nuclear membrane biogenesis and behavior during the mitotic divisions of the Drosophila embryo.

Recently, regional changes of cytokeratin patterns in human normal non-keratinized or keratinized oral mucosa have been demonstrated and the expression of individual cytokeratin polypeptides in lesions of oral mucosa has been compared with that of normal tissues. In particular, the presence of cytokeratin 19 in the suprabasal cell layers of oral epithelia has been shown to be strongly correlated with premalignancy. In the present study, we describe the results of an immunohistochemical investigation performed using a monoclonal antibody specific for cytokeratin 1 on normal oral mucosa and benign or malignant oral lesions. We show the different distribution of this polypeptide in non-neoplastic lesions from different sites of oral mucosa and describe the presence of cytokeratin 19. Our results are in agreement with the data obtained previously. In the malignant cases we demonstrate that the distribution of the two cytokeratins is characterized by complementary patterns.

Background Streptococcus pneumoniae is the leading cause of bacterial meningitis. Pneumococcal meningitis is associated with the highest mortality among bacterial meningitis and it may also lead to neurological sequelae despite the use of antibiotic therapy. Experimental animal models of pneumococcal meningitis are important to study the pathogenesis of meningitis, the host immune response induced after infection, and the efficacy of novel drugs and vaccines.

Idiopathic retroperitoneal fibrosis or Ormond's disease is a fibrotic process that encircles the lower abdominal aorta and frequently causes bilateral ureteral obstruction. Generally this process is limited by the renal fascia, diaphragm, brim of the pelvis and ureters. Variants exist with massive spreading to the thorax and pelvis or sharply circumscribed localization around the bladder or 1 kidney.' Retroperitoneal structures are displaced and encased by fibrous tissue but not infiltrated. Idiopathic retroperitoneal fibrosis may be associated with a similar process in the mediastinum, sclerosing cholangitis, Riedel's thyroiditis (only 15 cases including ours collected from studies worldwide),' pseudotumor of the orbit or generalized vasculitis. We describe an unusual case of aggressive idiopathic retroperitoneal fibrosis associated with Riedel's thyroiditis. The peculiarity of our case was unilateral spreading with massive left kidney infiltration, simulating malignant neoplasia. sider and treat it as a malignant lesion. Considering the massive involvement of the renal hilum, nephrectomy was the therapy of choice. The correct diagnosis was made only after microscopic examination.