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Small cell tumors arise from the neuroendocrine cell system and they are most frequently found in the lung (SCLC). Small cell tumor could occasionally arise in other body sites, such as the cervix, prostate, gastrointestinal tract, and very rarely from other sites. Metastatic SCLC patients present with metastatic disease in 80% of cases, and the metastases typically are reported in brain, liver, lung, and bone; they rarely could be found in the ovary. Differently, primitive small cell carcinoma of the ovary of pulmonary type is a rare and highly aggressive tumor arising from the ovarian cells; no suitable treatment strategy has been established yet. In this paper, we talk about a 72-year-old woman who presented with abdominal bleeding and a large mass in her pelvic region. A primary ovarian carcinoma was suspected, and she underwent hysterectomy with laparoscopic surgery and bilateral oophorectomy, lymph node resection, omentectomy, complementary appendix and sigmoid resection. The postoperative pathologic diagnosis was a differential diagnosis between small cell ovarian carcinoma of the pulmonary type and metastasis of SCLC.

Background Rosette-forming glioneuronal tumors (RGNTs) with multifocal growth throughout the ventricular system are extremely rare, and only 1 case of RGNT with dissemination limited to supratentorial ventricles has previously been reported. Recent evidence based on molecular data suggest that low-grade glioneuronal tumors (GNT) involving the septum pellucidum and the lateral ventricles, with either dysembryoplastic neuroepithelial tumor-like or RGNT-like features, may belong to a neuropathologic entity distinct from cortical dysembryoplastic neuroepithelial tumor and “typical” fourth ventricle RGNT, respectively. Given their rarity, the classification of these neoplasms is still uncertain and their clinicopathological and radiological aspects are only partially known. Case Description A 24-year-old male presented a GNT with RGNT-like morphological features centered in the septum pellucidum with multifocal masses occupying the lateral ventricles and the third ventricle with extraventricular infiltration of the frontal lobe. The patient underwent subtotal resection and 4 years follow-up. The clinicopathological and radiological features of the neoplasm are discussed. Conclusions Advanced magnetic resonance imaging (magnetic resonance spectroscopy and perfusion-weighted imaging) may provide valuable information in the differential diagnosis between rare GNTs and other more frequent intraventricular neoplasms. In the present case, the enhancing remnant portion of the tumor showed remarkable contrast enhancement variability during the follow-up with slow in situ progression. However, available data suggest that spontaneous contrast enhancement “fluctuations” over time in RGNT may not represent a reliable indicator of tumor behavior.

Mixed adenoneuroendocrine carcinoma (MANEC) is a rare tumor of the gastrointestinal tract involving both epithelial and neuroendocrine (NE) components, each of which represents at least 30% of the tumor. Because of the low frequency of this histotype, only a few cases have been described. In this report we discuss two cases treated with neoadjuvant chemotherapy: a pancreatic adenocarcinoma and a gastric adenocarcinoma. The histopathological specimens examined after surgery showed an additional NE component with a possible indication of the MANEC histotype. We hypothesize two possible explanations: tumor NE cells are more chemo-resistant than adenocarcinoma cells, and cytotoxic injury induces NE differentiation in tumor cells. The clinical significance and prognostic value of endocrine differentiation, however, remain controversial issues.

In total, ~25% of familial breast cancer (BC) is attributed to germline mutations of the BRCA1 and BRCA2 genes, while the rest of the cases are included in the BRCAX group. BC is also known to affect men, with a worldwide incidence of 1%. Epigenetic alterations, including DNA methylation, have been rarely studied in male breast cancer (MBC) on a genome-wide level. The aim of the present study was to examine the global DNA methylation profiles of patients with BC to identify differences between familial female breast cancer (FBC) and MBC, and according to BRCA1, BRCA2 or BRCAX mutation status. The genomic DNA of formalin-fixed paraffin-embedded tissues from 17 women and 7 men with BC was subjected to methylated DNA immunoprecipitation and hybridized on human promoter microarrays. The comparison between FBC and MBC revealed 2,846 significant differentially methylated regions corresponding to 2,486 annotated genes. Gene Ontology enrichment analysis revealed molecular function terms, such as the GTPase superfamily genes (particularly the GTPase Rho GAP/GEF and GTPase RAB), and cellular component terms associated with cytoskeletal architecture, such as ‘cytoskeletal part’, ‘keratin filament’ and ‘intermediate filament’. When only FBC was considered, several cancer-associated pathways were among the most enriched KEGG pathways of differentially methylated genes when the BRCA2 group was compared with the BRCAX or BRCA1+BRCAX groups. The comparison between the BRCA1 and BRCA2+BRCAX groups comprised the molecular function term ‘cytoskeletal protein binding’. Finally, the functional annotation of differentially methylated genes between the BRCAX and BRCA1+BRCA2 groups indicated that the most enriched molecular function terms were associated with GTPase activity. In conclusion, to the best of our knowledge, the present study was the first to compare the global DNA methylation profile of familial FBC and MBC. The results may provide useful insights into the epigenomic subtyping of BC and shed light on a possible novel molecular mechanism underlying BC carcinogenesis.

Serrated lesions represent a group of lesions with different genetic and biological features causing important clinical repercussions. Three types of serrated lesions are identified: hyperplastic, sessile adenomas (with and without dysplasia) and traditional serrated adenomas. Such lesions are now recognized as precancerous lesions.The carcinogenic process of serrated lesions follows a pathway including: alterations concerning activation of mitogen and protein kinase regulating the extracellular signal of other intracellular kinases (MAPK-ERK), inhibition of the apoptosis and hypermethylation of DNA and instability of microsatellites. Like for adenomatous polyps, the risk factors for serrated lesions are environmental factors, related to lifestyle and diet. The cancerogenic risk is increased by excessive alcohol consumption, obesity and poor intake of folate. When a high number of colorectal polyps with architecture serrated is diagnosed, it could be considered as serrated polyposis syndrome (SPS). According the most recent ESGE guidelines, the diagnostic criteria of the SPS, are: at least 5 polyps resected proximal to the sigmoid colon, 2 of which> 10 mm, or >20 serrated lesions of any size distributed in the entire colon. This condition presents a high risk for personal and/or familiar CRC, for this reason a regular screening colonoscopy should be performed in these patients and in their first-degree relatives. Serrated lesions represent a group of lesions with different genetic and biological features causing important clinical repercussions. Three types of serrated lesions are identified: hyperplastic, sessile adenomas (with and without dysplasia) and traditional serrated adenomas. Such lesions are now recognized as precancerous lesions.The carcinogenic process of serrated lesions follows a pathway including: alterations concerning activation of mitogen and protein kinase regulating the extracellular signal of other intracellular kinases (MAPK-ERK), inhibition of the apoptosis and hypermethylation of DNA and instability of microsatellites. Like for adenomatous polyps, the risk factors for serrated lesions are environmental factors, related to lifestyle and diet. The cancerogenic risk is increased by excessive alcohol consumption, obesity and poor intake of folate. When a high number of colorectal polyps with architecture serrated is diagnosed, it could be considered as serrated polyposis syndrome (SPS). According the most recent ESGE guidelines, the diagnostic criteria of the SPS, are: at least 5 polyps resected proximal to the sigmoid colon, 2 of which> 10 mm, or >20 serrated lesions of any size distributed in the entire colon. This condition presents a high risk for personal and/or familiar CRC, for this reason a regular screening colonoscopy should be performed in these patients and in their first-degree relatives.

Primary melanoma of the lung is an extremely rare clinical entity. We found only 32 cases reported in literature, and in two of these multiple brain metastases were present. We describe a case of primary lung melanoma with brain and skin metastases that presented with an initial clinical diagnosis of pneumonia.A 55-year-old white man presented with cough productive of dark sputum and fever. A chest x-ray showed a right lung infiltration. After failure to respond to usual treatment for pneumonia, bronchoscopy examination and CT scan revealed a right pulmonary mass. The CT-guided biopsy confirmed a diagnosis of malignant melanoma. The primary lung origin of the tumor was demonstrated by the characteristic junctional pattern of melanoma cells. Further evaluation revealed metastases in the brain and in skin.Primary lung melanoma is an uncommon neoplasm that may be confused with more conventional types of lung cancer. Careful interpretation of histopathological information in correlation with all other clinical, laboratory and imaging studies may be needed to establish a diagnosis. Evaluation for metastases should include looking at the eyes, brain, skin. Due to the small number of cases reported in literature, there is no experience on the management and the prognosis of the disease.

Summary A case of malignant epithelioid schwannoma in the skin is reported. This was a rare variant of a malignant tumour that arose on the back of a 35-year-old male without neurofibromatosis. Clinically the nodule appeared to be a benign cyst but as it was painful it was decided to remove it. Ultrastructural and immunohistochemical features of the lesion were consistent with those of malignant epithelioid schwannoma so a radical excision was performed. Most ordinary malignant schwannoma are located in the deep soft tissue of the proximal portions of the upper and lower extremities and trunk; to the best of our knowledge only 26 cases of malignant epithelioid schwannoma in the skin and subcutis have been described in the literature. For the 14 male and 12 female patients reviewed, the median age was 43 years (range 19–84). Upper extremities were the most common sites (10 of 26). Seven patients developed local recurrences and four developed metastases: two to lung, one to lung and lymph node, and one to lung, liver and brain. All patients with local recurrence and all except one who developed metastases did not undergo wide local excision. We can conclude that malignant epithelioid schwannoma in the skin and subcutis is eminently curable if treated with wide local excision.

Carcinoid tumors are endocrine malignancies that are often associated with a characteristic syndrome, the malignant carcinoid syndrome, which is most common in patients with small bowel tumors and liver metastases. In the rare instances when the syndrome is present without liver metastases the primary tumor is usually localized to the bronchus or ovary and secretes hormones directly into the systemic circulation. About two thirds of patients with carcinoid syndrome have evidence of carcinoid heart disease. We report on a case of a primary ovarian carcinoid tumor with an unusual clinical presentation.

Clear cell thymic carcinoma is a rare and invasive tumor of the mediastinum for which there are no uniform treatment guidelines. The combination of carboplatin plus paclitaxel seems to be the most effective regimen for this disease. We report a case of locally advanced clear cell thymic carcinoma treated with this schedule, in which we observed a relevant and rapid tumor shrinkage.

A complementary DNA (cDNA) library was constructed from a human malignant mesothelioma (MM) cell line and a cDNA fragment encoding for a cytoplasmic mesothelial protein recognized by the polyclonal antibody AMAD-1 was then cloned and expressed in Escherichia coli. The purified recombinant protein was used to raise a novel antibody, named AMAD-2, in rabbits. This antibody reacted with normal mesothelium and most MM (15 of 17) on paraffin sections and featured a cytoplasmic labeling. Conversely, AMAD-2 immunostaining of normal and tumor tissues from body sites other than serosal membranes was limited with respect to the proportion of positive specimens and usually less conspicuous than in MM. AMAD-2 immunoreactivity was subsequently compared with staining for HBME-1, another newly marketed antimesothelial monoclonal antibody, concerning the ability to distinguish pleural MM from metastatic pleural tumors of epithelial type. A granular cytoplasmic immunoreactivity for AMAD-2 was present in 50% or more of tumor cells in all 84 MM, regardless of histological type, but also in 3 (7%) of 42 pleural metastases, albeit only focally. HBME-1 was shown in 63 of 66 epithelial MM and in the epithelial component of all 8 mixed MM, with a prevailingly membranous pattern, usually homogeneous and strong, whereas none of the 10 sarcomatous MM was positive. HBME-1 was also expressed in 6 (14%) of 42 pleural metastases in a cytoplasmic or membranous pattern. Compared with HBME-1, AMAD-2 showed a higher degree of specificity and sensitivity for MM. AMAD-2 still proved to be superior to HBME-1, also when sarcomatoid MM were excluded from the assessment. This finding supports the view that AMAD-2 is an antibody highly, although not entirely, specific for the mesothelial lineage, whereas HBME-1 is probably a cell marker more closely related to the epithelial differentiation of MM. Therefore, AMAD-2 is preferable as a positive tissue marker to be incorporated in the optimal immunohistochemical panel for the diagnosis of MM.

Management of locally advanced NSCLC is controversial. Induction chemotherapy followed by surgery has become an accepted approach for State III disease. However, the clinical assessment of the efficacy of preoperative treatment is inaccurate. We propose a four-grade histopathological evaluation of the response to chemotherapy based on the analysis of 20 evaluable cases and compared with clinical outcome. Follow-up ranged from 12 to 68 months. Correlation between different grading of necrosis and survival is statistically significant. Based on these preliminary results, we suggest that grading of response is a valid parameter to evaluate standard regimens and novel drug associations in larger trials.

Clear cell adenocarcinoma arising in the lower urinary tract is unusual. We report a case of clear cell adenocarcinoma of the bladder in a 54-year-old male. Cystoscopic examination revealed a tumour arising from the dome of the urinary bladder. Histologically, the tumour was chiefly composed of tubulocystic and papillary glands lined by glycogen-rich, cubical or hobnail cells with clear to eosinophilic cytoplasm. The tumour infiltrated into the inner muscular layer. The patient was treated by partial cystectomy.

A 61-year-old man attended for a 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT); he underwent a CT scan with contrast medium 2 days before, which showed numerous peritoneal nodules. He also had high levels of alpha-fetoprotein (500 mg/ml, normal < 20 mg/ml). 18F-FDG PET/CT showed an extended peritoneal involvement (Fig. 1a,b, and c); multiple pulmonary bilateral nodules and abdominal lymph nodes also had high levels of FDG uptake (Fig. 1d). Maximum standard uptake value (SUVmax) of the peritoneal lesions was 19.2. No clear primary could be found; in particular, no isolated uptakes in gastrointestinal tract could be detected, and pulmonary nodules were bilateral and small.

The desmoid tumor is a rare tumor with an incidence of 2–4 cases per million people each year, and represents 0.03% of all cancers. The tumor is composed of fibrous tissue that produces masses of well-differentiated hard elastic consistency. According to their site of onset, the desmoid tumors are classified in abdominal, intra-abdominal, and extra-abdominal. The abdominal cases develop inside the abdominal muscles of the abdominal wall upright, especially in women in their 2nd - 4th decade of life, particularly in those who have been pregnant. Methods A 66-year-old patient underwent nephrectomy in 2006 for the detection of a massive tumor in the right kidney (EI: pT1bNx). The patient came to our observation for the radiological tracking (CT) of a solid lesion of 4 cm below the right arch, 2 years after surgery. For this reason it was decided to refer the patient to a series of percutaneous biopsies. The report describes a histologic lesion of fibromatosis. After one year a new CT exam showed a significant increase of the size of the lesion, with a diameter of 11.6 x 7.9 cm, and abdominal involvement to ascending colon. Given the discrepancy between the CT data and the histological report, it was decided to refer the patient to a lombotomic exploration and the subsequent removal of the lesion, which appeared of hard, elastic consistency and well capsulated. The final histology test confirmed the fibromatosis lesion. Conclusions The desmoid tumor is a rare tumor characterized by the proliferation of fibrotic tissue. The tumor is composed of well-differentiated fibrous tissue and has a hard-elastic consistency. Regarding the development of dermoid tumors, several risk factors were identified, including extra-abdominal fibromatosis, genetic factors, endocrine factors. Other causes may arise from trauma or abdominal injury in surgical outcomes of appendectomy, laparotomy and other surgical scars (scar fibromatosis) or genetic predisposing factors. The surgical resection of dermoid tumors should be the therapy of choice, complete and radical, to cover the possible excision of a wide margin of surrounding structures concerned, and those arrangements should ensure a low rate of relapse. However, in cases of inoperable cancer due to extension, anti-estrogen therapy may have an important therapeutic and well-tolerated effect, besides being relatively non-toxic, even at high doses. A close follow-up is indicated, however, and warmly recommended.

Background: Epidermal growth factor receptor (EGFR) promoter methylation may be responsible for the loss of EGFR expression in neoplastic cells. The primary aim of our study was to verify a possible correlation between EGFR gene promoter methylation and clinical outcome in metastatic colorectal cancer patients receiving chemotherapy with irinotecan and cetuximab. Methods: Colorectal samples from patients treated with irinotecan–cetuximab were analysed for EGFR promoter methylation and EGFR immunohistochemistry. Results: Fifty-two patients were analysed. Thirty patients (58%) showed EGFR promoter hypermethylation. In EGFR promoter methylated and EGFR promoter unmethylated patients, we observed a partial response in 3 (10%) and 13 (59%) patients, respectively (P=0.03), progressive disease was obtained in 19 (63%) and 2 (9%) patients, respectively, with EGFR promoter methylated and EGFR promoter unmethylated tumours (P=0.0001). Median progression-free survival was 2.4 months in patients showing EGFR promoter methylated tumours and 7.4 months for those who had EGFR promoter unmethylated tumours (P

Colorectal tumorigenesis is one of the best known processes of cellular transformation in humans. Its characterization has moved ahead by leaps and bounds during the last three decades thanks to major advances in the fields of endoscopy, histology and molecular pathology. And as often happens when a human disease is subjected to in-depth investigation, what originally appeared to be a single entity turns out to include several distinct clinical, histologic, and molecular phenotypes. Among other things, tumor phenotypes can tell us a great deal about the route taken by the tumor cells on their journey toward malignancy. Not surprisingly, some tumors develop along pathways that are “heavily ­ trafficked” (and for this reason, relatively well known); others follow the “roads less traveled.” But if obstacles arise along the way, tumor cells are adept at exploiting alternative routes that permit them to continue their journey toward cancer, and these deviations can give rise to mixed phenotypes. These phenotypes are nonetheless consistent with the concept of carcinogenesis as a nonrandom – and therefore, predictable – process. Each pathway, each crossroads is the result of a specific set of genetic or epigenetic alterations. Many are already well defined, others are only partially characterized, and some are still in the realm of hypothesis. Thus far, we have fairly reliable maps of at least two of the major pathways to colorectal cancer, but with increasingly sophisticated molecular analysis of preinvasive lesions, there is little doubt that we will eventually identify variants of these pathways and uncover others whose existence was not even suspected.

To clarify the role of epidermal growth factor receptor (EGFR) promoter methylation in primary colorectal cancers and corresponding metastases and its relationship to EGFR expression.Formalin-fixed tumor samples (primary site and metastasis)from colorectal cancer patients were analyzed for EGFR promoter methylation and EGFR immunohistochemistry expression.Among the 63 assessable patients, 25 cases (39.7%) showed EGFR promoter methylation. Forty-two primary colorectal tumors and corresponding metastases were available for paired analysis of EGFR methylation status. EGFR methylation status of the primary tumor was in accordance with that of metastasis in 29 patients (69%). In contrast, 7 patients (50%) with EGFR promoter methylation in the primary tumor showed unmethylated EGFR in metastasis, and 6 metastases (46%) showed EGFR promoter hypermethylation derived from unmethylated EGFR primary tumors. Lack of EGFR protein expression was observed in 8 EGFR promoter methylated primary tumors (44%) and in 7 EGFR promoter methylated metastatic sites (44%).EGFR promoter hypermethylation does not seem to represent a rare event in colorectal cancer and may be present differently in different tumor sites. These findings may be relevant to further studies investigating the role of EGFR in colorectal cancer patients.

Malignant salivary gland neoplasms in children are rare, most common being mucoepidermoid carcinoma, adenoid cystic carcinoma, acinic cell carcinoma and adenocarcinoma. Most germ-cell neoplasms of head and neck in children are teratomas. The authors report a case of endodermal sinus tumor (EST) of the parotid gland in a 2-year-old girl, which recurred after chemotherapy. The role of alpha-fetoprotein (AFP) serum level as a helpful marker in differential diagnosis and in evaluating tumor progression is underlined.

Background K-RAS wild type colorectal tumors show an improved response rate to anti-EGFR monoclonal antibodies. Nevertheless 70% to 40% of these patients still does not seem to benefit from this therapeutic approach. FISH EGFR GCN has been previously demonstrated to correlate with clinical outcome of colorectal cancer treated with anti-EGFR monoclonal antibodies. CISH also seemed able to provide accurate EGFR GCN information with the advantage of a simpler and reproducible technique involving immunohistochemistry and light microscopy. Based on these findings we investigated the correlation between both FISH and CISH EGFR GCN and clinical outcome in K-RAS wild-type colorectal cancer treated with irinotecan-cetuximab. Methods Patients with advanced K-RAS wild-type, colorectal cancer receiving irinotecan-cetuximab after failure of irinotecan-based chemotherapy were eligible. A cut-off value for EGFR GCN of 2.6 and 2.12 for FISH and CISH respectively was derived from ROC curve analysis. Results Forty-four patients were available for analysis. We observed a partial remission in 9 (60%) and 2 (9%) cases with a FISH EGFR GCN ≥ 2.6 and < 2.6 respectively (p = 0.002) and in 10 (36%) and 1 (6%) cases with a CISH EGFR GCN ≥ 2.12 and < 2.12 respectively (p = 0.03). Median TTP was 7.7 and 6.4 months in patients showing increased FISH and CISH EGFR GCN whereas it was 2.9 and 3.1 months in those with low FISH and CISH EGFR GCN (p = 0.04 and 0.02 respectively). Conclusion FISH and CISH EGFR GCN may both represent effective tools for a further patients selection in K-RAS wild-type colorectal cancer treated with cetuximab.

Bone marrow (BM) multipotent mesenchymal stromal cells (MSCs) present with multipotent differentiation potential and immunomodulatory properties. As an alternative to bone marrow, we have examined fetal membranes, amnion and chorion, of term human placenta as a potential source of multipotent MSCs. Here we show that amnion mesenchymal cells (AMCs) and chorion mesenchymal cells (CMCs), isolated by mechanical separation and subsequent enzymatic digestion, demonstrate plastic adherence and fibroblast-like morphology and are able to form colonies that could be expanded for at least 15 passages. By FACS analysis, AMCs and CMCs were shown to be phenotypically similar to BM-MSCs and, when cultured in differentiation media, they demonstrated high morphogenetic plasticity by differentiating into osteocytes, chondrocytes and adipocytes. In an attempt to isolate cells with MSC characteristics from human fetal membranes, AMCs and CMCs expressing CD271 were enriched by immunomagnetic isolation and were demonstrated to possess higher clonogenic and osteogenic differentiation potential than CD271-depleted fractions. Based on these findings, amnion and chorion can be considered as a novel and convenient source of adult MSCs.

Primary neoplasia of the heart is rare and often diagnosed postmortem (with a prevalence0.2% at postmortem examinations) due to the lack of specific clinical symptoms and signs. Among benign cardiac tumors, cavernous hemangioma has a prevalence of 2.8%. Less invasive diagnostic techniques such as transthoracic echocardiography allow for the diagnosis to be made during life with definitive surgical treatment. We report a representative case of right ventricular cavernous hemangioma, which mimicked right ventricular failure associated with systolic pulmonary flow tract obstruction. Surgical treatment was indicated for symptom severity and for the unpredictable behavior of the large neoplasm.

Syringotropic cutaneous T cell Lymphoma (SCTCL) is a rare localized variant of CTCL. It is characterized by erythematous papules that, at histological examination, show dense dermal infiltrates of atypical T cells, that are preferentially located around hyperplastic eccrine sweat glands and ducts, with absent or minimal epidermotropism. Its relationship with mycosis fungoides and other CTCLs is not clarified and is still under discussion. Several treatment approaches have been suggested, but therapeutic results are often disappointing. We report the case of a patient with typical clinical and histopathological features of SCTCL and an excellent response to PUVA therapy.

BACKGROUND: Fetal membranes are tissues of particular interest for several reasons, including their role in preventing rejection of the fetus and their early embryologic origin. which may entail progenitor potential. The immunologic reactivity and the transplantation potential of amnion and chorion cells, however, remain to be elucidated. METHODS: Amnion and chorion cells were isolated from human term placenta and characterized by immunohistochemistry, flow cytometric analysis, and expression profile of relevant genes. The immunomodulatory characteristics of these cells were studied in allogeneic and xenogeneic mixed lymphocyte reactions and their engraftment potential analyzed by transplantation into neonatal swine and rats. Posttransplant chimerism was determined by polymerase chain reaction analysis with probes specific for human DNA. RESULTS: Phenotypic and gene expression studies indicated mesenchymal stem cell-like profiles in both amnion and chorion cells that were positive for neuronal, pulmonary, adhesion, and migration markers. In addition, cells isolated both from amnion and chorion did not induce allogeneic nor xenogeneic lymphocyte proliferation responses and were able to actively suppress lymphocyte responsiveness. Transplantation in neonatal swine and rats resulted in human microchimerism in various organs and tissues. CONCLUSIONS: Human amnion and chorion cells from term placenta can successfully engraft neonatal swine and rats. These results may be explained by the peculiar immunologic characteristics and mesenchymal stem cell-like phenotype of these cells. These findings suggest that amnion and chorion cells may represent an advantageous source of progenitor cells with potential applications in a variety of cell therapy and transplantation procedures.

The differential diagnosis of Cushing's syndrome is one of the most difficult tasks in medicine, and it is especially problematic in cases with “occult” ectopic ACTH syndrome. We describe the case of a 26-year-old woman who was found to suffer from ectopic ACTH syndrome due to pituitary microadenoma, localized within a mature ovarian teratoma. Cushing's syndrome caused by ovarian neoplasia is unusual, but when it occurs, it is most often due to excessive cortisol production by the ovary. Only rarely has ectopic ACTH syndrome in association with an ovarian tumor been described.

Skin metastases from internal malignancies are rare, particularly those originating from carcinoma of the cervix: only 11 cases have been reported in the medical literature since 1940. We describe the case of a cutaneous metastases from a squamous-cell carcinoma of the cervix that was solitary, unusual for its location, and with the longest survival reported so far.

Purpose NF-kB expression has been shown to be responsible for resistance to antineoplastic agents and it also plays a part in the activation of the epidermal growth factor receptor downstream signaling pathway in colorectal tumors. The aim of our analysis was to investigate a correlation between NF-kB expression, response rate, time to progression, and survival in advanced colorectal cancer patients receiving cetuximab and irinotecan. Patients and Methods We analyzed retrospectively the immunoreactivity for NF-kB in irinotecan-refractory patients receiving cetuximab and irinotecan. Results Seventy-six patients were analyzed. Cetuximab and irinotecan were administered as second-line chemotherapy in 19 patients and after ≥ two lines of chemotherapy in the remaining 57 patients. We observed a partial response (PR) in 16 patients for an overall response rate of 24%. Thirty-two patients (48%) experienced progressive disease; median time to progression (TTP) was 3.6 months and median overall survival was 10.3 months. NF-kB was positive in 46 patients (60%). All main clinical characteristics were well balanced between NF-kB–positive and NF-kB–negative patients. The response rate was 10% (four PRs) versus 48% (12 PRs; P = .0007) in NF-kB–positive and NF-kB–negative tumors, respectively. Median TTP in NF-kB–positive patients was 3 v 6.4 months in the remaining patients (P = .021). Median overall survival was 9.5 v 15.8 months for NF-kB–positive and NF-kB–negative patients, respectively (P = .036) Conclusion The difference in median TTP, overall survival, and response rate seem to confirm that NF-kB may play a crucial role in predicting the efficacy of cetuximab and irinotecan in advanced colorectal tumors.

We present four cases of infantile cerebellar neoplasms composed of cells with large vesicular nuclei with prominent nucleoli. All four cases were strongly immunoreactive for synaptophysin, and one case showed immunoreactivity for neurofilaments. Filter hybridization for N-myc and c-myc oncogenes showed a 27-fold c-myc amplification in one case. The cytogenetic analysis in this case showed Double-Minutes and isochromosome 17q. An intracerebral xenograft in nude mice obtained from one such tumor showed a similar morphology to that of the original tumor as well as strong immunoreactivity for synaptophysin and neurofilaments. All the neoplasms were characterized by highly aggressive behavior leading to early cerebrospinal fluid dissemination despite radiotherapy and chemotherapy. We conclude that large-cell medulloblastoma represents a distinct and more aggressive variant of medulloblastoma that requires more aggressive therapy.

Improved colonoscopy is revealing precancerous lesions that were frequently missed in the past, and ∼30% of those detected today have nonpolypoid morphologies ranging from slightly raised to depressed. To characterize these lesions molecularly, we assessed transcription of 23,768 genes in 42 precancerous lesions (25 slightly elevated nonpolypoid and 17 pedunculated polypoid), each with corresponding samples of normal mucosa. Nonpolypoid versus polypoid morphology explained most gene expression variance among samples; histology, size, and degree of dysplasia were also linked to specific patterns. Expression changes in polypoid lesions frequently affected cell-cycling pathways, whereas cell-survival dysregulation predominated in nonpolypoid lesions. The latter also displayed fewer and less dramatic expression changes than polypoid lesions. Paradigmatic of this trend was progressive loss through the normal > nonpolypoid > polypoid > cancer sequence of TMIGD1 mRNA and protein. This finding, along with TMIGD1 protein expression patterns in tissues and cell lines, suggests that TMIGD1 might be associated with intestinal-cell differentiation. We conclude that molecular dysregulation in slightly elevated, nonpolypoid, precancerous colorectal lesions may be somewhat less severe than that observed in classic adenomatous polyps.