A case of myoepithelioma mimicking a parotid cyst.

Myoepithelioma is an uncommon tumor of the myoepithelial cells that is considered to represent a distinct category of tumor by the World Health Organization. It accounts for less than 1% of all tumors that develop in the salivary glands. We describe the case of a 35-year-old woman who presented to us with a painless swelling on the right side of her face. She was diagnosed with a parotid gland cyst by ultrasonography and computed tomography. Following excision of the mass, however, the pathology report identified the tumor as a solid myoepithelioma. To the best of our knowledge, this is the first reported case of a myoepithelioma that exhibited cystic features on radiologic examination even though it had a solid architecture. We also discuss the preoperative diagnostic aspects of the myoepitheliomas.

The selective expression of ret finger protein in endometrial cancer: can RFP be a marker of serous carcinomas?

OBJECTIVE: Endometrial cancer is a common malignancy of the gynecological system and has been classified into two major groups, Types I and II. Type I tumors are estrogen-related, low-grade endometrioid tumors, whereas type II tumors are aggressive, high-grade non-endometrioid tumors. Ret finger protein is a nuclear transcription factor with a tripartite motif that is highly expressed in different tumor cells. MATERIAL AND METHOD: To analyze the expression of ret finger protein in endometrial tissues and cancer, 18 cases of secretory and proliferative endometrium, endometrial polyp, endometrial hyperplasia and endometrial intraepithelial neoplasia and 21 cases of types I and II endometrial carcinoma were evaluated immunohistochemically. RESULTS: Although rare cases of secretory endometrium showed a weak focal nuclear positivity, remaining proliferative endometrium, endometrial hyperplasia and type I endometrioid cancer cases were negative. In contrast, all cases of serous cancers showed strong nuclear positivity. After these strong positive results for serous endometrial cancer, 12 more cases of ovarian and endometrial serous carcinoma cases were added to the study. All of the additional cases were also strongly positive for ret finger protein. CONCLUSION: We suggest that ret finger protein might play a role in the carcinogenesis of the serous tumors of gynecological system and can be used to differentiate serous carcinomas from other epithelial tumors.

Ulcerative colitis-associated colorectal cancer arises in a field of short telomeres, senescence, and inflammation.

Inflammation plays a role in the progression to cancer and it is linked to the presence of senescent cells. Ulcerative colitis (UC) is a chronic inflammatory disease that predisposes to colorectal cancer. Tumorigenesis in this setting is associated with telomere shortening that can be observed in the nondysplastic epithelium of UC patients with high-grade dysplasia (HGD) or cancer (UC progressors). We hypothesized that a preneoplastic field of inflammation, telomere shortening, and senescence underlies tumor progression in UC progressors. Multiple biopsies of varying histologic grade were collected along the colon of nine UC progressors and analyzed for telomere length, DNA damage, senescence, p53, p16, and chronic and acute inflammation. Twenty biopsies from four UC nonprogressors and twenty-one biopsies from control individuals without UC were also analyzed. Short telomeres and increased DNA damage, senescence, and infiltrating leukocytes were observed in biopsies located less than 10 cm from HGD or cancer. Low-grade dysplasia (LGD) had the shortest telomeres along with the highest levels of senescence and infiltrating leukocytes, whereas HGD biopsies showed the opposite pattern. The expression of p16 and p53 was low in nondysplastic biopsies but progressively increased in LGD and HGD. In addition, high levels of infiltrating leukocytes were associated with telomere shortening, senescence, and reduced p53 expression. These results suggest that dysplasia arises in a preneoplastic field of chronic inflammation, which leads to telomere shortening, DNA damage, and senescence. Our findings argue that senescence acts as a tumor suppressor mechanism that is abrogated during the transition from LGD to HGD in UC.

Aberrant expression of DNA damage response proteins is associated with breast cancer subtype and clinical features.

Landmark studies of the status of DNA damage checkpoints and associated repair functions in preneoplastic and neoplastic cells has focused attention on importance of these pathways in cancer development, and inhibitors of repair pathways are in clinical trials for treatment of triple negative breast cancer. Cancer heterogeneity suggests that specific cancer subtypes will have distinct mechanisms of DNA damage survival, dependent on biological context. In this study, status of DNA damage response (DDR)-associated proteins was examined in breast cancer subtypes in association with clinical features; 479 breast cancers were examined for expression of DDR proteins γH2AX, BRCA1, pChk2, and p53, DNA damage-sensitive tumor suppressors Fhit and Wwox, and Wwox-interacting proteins Ap2α, Ap2γ, ErbB4, and correlations among proteins, tumor subtypes, and clinical features were assessed. In a multivariable model, triple negative cancers showed significantly reduced Fhit and Wwox, increased p53 and Ap2γ protein expression, and were significantly more likely than other subtype tumors to exhibit aberrant expression of two or more DDR-associated proteins. Disease-free survival was associated with subtype, Fhit and membrane ErbB4 expression level and aberrant expression of multiple DDR-associated proteins. These results suggest that definition of specific DNA repair and checkpoint defects in subgroups of triple negative cancer might identify new treatment targets. Expression of Wwox and its interactor, ErbB4, was highly significantly reduced in metastatic tissues vs. matched primary tissues, suggesting that Wwox signal pathway loss contributes to lymph node metastasis, perhaps by allowing survival of tumor cells that have detached from basement membranes, as proposed for the role of Wwox in ovarian cancer spread.

Study of FHIT and WWOX expression in mucoepidermoid carcinoma and adenoid cystic carcinoma of salivary gland.

Mucoepidermoid carcinoma (MEC) and adenoid cystic carcinoma (ACC) are salivary gland neoplasms with divergent morphological features and clinical behavior. ACC is a basaloid tumor whereas MEC is a glandular epithelial neoplasm. FHIT and WWOX are tumor suppressor genes that encompass the FRA3B and FRA16D fragile sites at chromosomes 3p14.2 and 16q23.3, respectively. In previous studies, we have shown concordant loss of Fhit and Wwox expression in breast cancer, with significantly more frequent loss in cancers of basal-like phenotype. To determine if there is a similar association in salivary gland neoplasms, we designed a study of MEC and ACC of salivary gland on tissue microarrays (TMA). TMAs were constructed from 25 MEC and 19 ACC of salivary gland. Fhit and Wwox protein expression was assessed by immunohistochemical staining of cores on TMAs. Correlations among immunohistochemical markers and histological type were determined by statistical analyses. Significantly reduced Fhit and Wwox expression was observed in ACC (p=0.002 and p<0.001, respectively). The results suggest that, as for breast cancer, loss of Fhit and Wwox expression might have a role in the pathogenesis of basaloid differentiation in salivary gland neoplasms; alternatively, differences in chromatin structure at chromosome fragile regions might make fragile genes more accessible to DNA damage and rearrangement early during preneoplastic stages of basaloid cancers. Studies of basaloid tumors of other organ systems may show similar results and these findings may have implications for treatment modalities designed for basal-like tumors.

Successful outpatient management of pelvic actinomycosis by ceftriaxone: a report of three cases

Pelvic actinomycosis is a chronic granulomatous suppurative disease caused by actinomyces israeli. Intravenous penicillin is the preferred antimicrobial but it requires hospitalization up to one month. An outpatient treatment strategy would be cost effective and a good choice for patients. Here we present three cases in which intramuscular ceftriaxone was successfully used in the outpatient settings following surgery and IV penicillin treatment in the hospital.

Isolated extraocular muscle involvement as the ophthalmic manifestation of leukaemia.

BACKGROUND: Clinical and imaging features of patients with orbital leukaemia primarily involving extraocular muscles were evaluated. METHODS: This retrospective case series includes patients with leukaemia whose only ophthalmic manifestation was extraocular muscle enlargement. Demographic data, clinical information on the systemic disease, prominent ocular signs and symptoms, computed tomography and magnetic resonance imaging characteristics, treatments applied and the outcomes were collected. RESULTS: Five patients were diagnosed as leukaemic infiltration of extraocular muscle between 1995 and 2008. The age at presentation ranged between 3 and 61 years. Acute myeloid leukaemia was the diagnosis in two patients, and chronic lymphocytic leukaemia, chronic myeloid leukaemia and biphenotypic acute leukaemia were found in one patient each, respectively. One patient had bilateral involvement. The lateral rectus muscle was affected in four patients and the superior rectus muscle in one case. Restricted ocular motility was the most common finding. In one patient who had no prior history of leukaemia, an incisional biopsy established the diagnosis. All patients received multi-agent chemotherapy. Four patients expired after a rapid decline of the systemic status within a mean period of 7 months. CONCLUSIONS: Leukaemic infiltration of extraocular muscles is a rare and late manifestation of the advanced disease associated with relapse and there seems to be a predilection for the lateral rectus muscle. Systemic prognosis remains dismal despite intensive chemotherapy.

Fragile histidine triad protein, WW domain-containing oxidoreductase protein Wwox, and activator protein 2gamma expression levels correlate with basal phenotype in breast cancer.

BACKGROUND: The expression of fragile histidine triad protein (Fhit) and WW domain-containing oxidoreductase protein (Wwox), tumor suppressors that are encoded by fragile (FRA) loci FRA3B and FRA16D, are lost concordantly in breast cancers. In the current study, the authors examined correlations among Fhit, Wwox, the activator protein 2 transcription factors AP2alpha and AP2gamma, cytokeratins 5 and 6 (CK5/6), epidermal growth factor receptor (EGFR), estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) and their associations with breast cancer phenotypes. METHODS: Tissue microarrays constructed from 837 breast cancer blocks were immunostained. Expression in >10% of tumor cells was considered positive for cytoplasmic CK5/6, membranous EGFR, and nuclear AP2alpha and AP2gamma. Cytoplasmic Fhit and Wwox staining was scored according to staining intensity. ER, PR, and HER-2 status of tumors was derived from records. Correlations among immunohistochemical markers and tumor subtypes were assessed by univariate and multivariate statistical methods. RESULTS: Triple-negative tumors had more frequent expression of EGFR, CK5/6 (P < .001), and AP2gamma (P = .003) and more frequent loss of Fhit and Wwox (P < .001), and an inverse correlation was observed between Fhit, Wwox expression and EGFR, ER, and PR expression (P < .001). Reduced Fhit expression was more common in HER-2-positive and AP2gamma-positive cases (P < .001 and P = .002, respectively). There was a direct correlation noted between Fhit and Wwox (P < .001) and a borderline positive relation between AP2alpha and AP2gamma (P = .054). CONCLUSIONS: The results from this investigation suggested that reduced expression levels of Fhit, Wwox, and nuclear AP2gamma have roles in the pathogenesis of basal-like differentiation in breast cancer. Alteration in the expression of fragile site genes occurs in most of these cancers and may contribute to defects in DNA repair, as observed in breast cancer 1 (BRCA1)-deficient cancers. Thus, DNA damage response checkpoint proteins may be targets for treatment.

Primary osteosarcoma of the urinary bladder following cyclophosphamide therapy for systemic lupus erythematosus: a case report.

INTRODUCTION: The association of systemic lupus erythematosus with malignancies is an uncommon occurrence. We present the case of an osteosarcoma of the urinary bladder developing in a patient with a prolonged history of active systemic lupus erythematosus. This is a previously unreported association. Primary osteosarcoma is an extremely rare disease in the urinary bladder. CASE PRESENTATION: A 24-year-old Caucasian woman with a 13-year history of systemic lupus erythematosus, who had been treated with high dose immunosuppressive agents, presented with pain and hematuria. A deeply invasive high-grade tumor was detected in the urinary bladder and the patient underwent radical surgery. A diagnosis of osteosarcoma was made based on the characteristic histology. CONCLUSION: Predisposing factors for primary sarcomas in the urinary bladder are mostly unknown; however, in our case, long-term administration of immunosuppressive agents, as well as long standing systemic lupus erythematosus, may both be of significance.

Prognosticators and the role of lymphadenectomy in uterine leiomyosarcomas.

OBJECTIVE: To analyze prognostic factors, the role of lymphadenectomy and postoperative adjuvant treatments in patients with uterine leiomyosarcomas (LMS). STUDY DESIGN: Sixty-three patients with uterine LMS are retrospectively analyzed with respect to both DFS and OS. RESULTS: Multivariate DFS analysis revealed percentage necrosis to be the unique factor to be significant (median DFS was 3.31 years for <25% necrosis and 0.78 for >25% necrosis). Multivariate analysis revealed the mitotic counts to be the unique significant factor affecting the OS (median OS was 7.20 and 1.73 years, respectively, for patients with mitotic counts of 1-5 and >6; respectively). Median DFS was 2.51 years for patients who had undergone lymphadenectomy and 2.36 years for remaining who did not have a lymphadenectomy procedure (P = 0.4). With respect to OS, median values were 2.44 and 3.16 years, respectively (P = 0.7). Number of the resected lymph nodes was also not significant for both OS and DFS. CONCLUSIONS: Mitotic counts and percentage necrosis have significant effects on OS and DFS; respectively. Neither the performance nor the extent of lymphadenectomy has an effect on patient survival.

Successful outpatient management of pelvic actinomycosis by ceftriaxone: a report of three cases.

Pelvic actinomycosis is a chronic granulomatous suppurative disease caused by actinomyces israeli. Intravenous penicillin is the preferred antimicrobial but it requires hospitalization up to one month. An outpatient treatment strategy would be cost effective and a good choice for patients. Here we present three cases in which intramuscular ceftriaxone was successfully used in the outpatient settings following surgery and IV penicillin treatment in the hospital.

Wwox and Ap2gamma expression levels predict tamoxifen response.

PURPOSE: Assessment of expression levels of Wwox, Wwox-interacting proteins Ap2alpha, Ap2gamma, and ErbB4, the Ap2gamma transcriptional target protein Her2, and the possible Ap2alpha transcriptional target PrkaRIalpha, in breast cancers, to determine their roles in tamoxifen resistance. The hypothesis was that sequestration of Wwox interactors in the cytoplasm might control tamoxifen response. EXPERIMENTAL DESIGN: Tissue sections from 51 tamoxifen-sensitive and 38 tamoxifen-resistant, estrogen receptor alpha-positive breast cancers were stained for the above proteins, as well as progesterone receptor (PR). The relation of tamoxifen resistance and other clinical features, with level of expression of these proteins, and pairwise correlations among various immunohistochemical markers were determined. RESULTS: Menopausal status, tumor, node, and stage, loss of PR, lost or reduced expression of Wwox, and high level of expression of PrkaRIalpha, Ap2gamma, and Her2 were significantly correlated with tamoxifen resistance. In multivariate analysis, Wwox, PrkaRIalpha, Ap2gamma, and ErbB4 were found to be independent markers of tamoxifen resistance. Reduced Wwox expression was better than PR in prediction of resistance, especially in high-risk patients, and nuclear Ap2gamma expression was better than Her2, especially in low-risk patients. CONCLUSION: The results illustrate the complex relationships among the marker proteins assessed in this in vivo study and suggest new markers for prediction of response to tamoxifen treatment as well as possible new targets for treatment of breast cancer. Wwox and Ap2gamma emerge as new biomarkers that may be superior to PR and Her2 in predicting tamoxifen response.

Omentectomy for gynecologic cancer: how much sampling is adequate for microscopic examination?

CONTEXT: Detecting omental metastasis is crucial for staging and treatment of endometrial and ovarian carcinoma. OBJECTIVE: To determine the optimal omental sampling for omentectomies to ascertain the stage of the disease in a cost-effective way. DESIGN: We reevaluated 258 omentectomies that were performed due to ovarian or endometrial carcinoma. A total of 116 cases were retrospectively studied, and 142 cases were prospectively studied. For prospective study, 10 to 16 blocks were sampled if the omentum showed no signs of gross tumor. Mean omental block sample frequency of 2 groups with the negative macroscopy but with or without microscopic tumor have been compared using an independent samples t test. RESULTS: Seven patients had no evidence of tumor metastasis on gross examination but had microscopic tumor metastasis. The mean numbers of blocks were 6.4 for patients having microscopic tumor without macroscopic involvement and 7.8 for patients having neither microscopic nor macroscopic involvement. Approximately twice as many samples were taken in the prospective analysis when compared with retrospective analysis. Two cases with microscopic omental metastasis that had no macroscopic involvement at first impression were reevaluated retrospectively and found to contain 0.3- to 0.5-cm white nodules. The rate of omental metastasis increased with the grade of the tumor (P = .005). CONCLUSION: Careful macroscopic examination is the most important step in detecting small omental metastasis. For cases with gross tumor, one section is sufficient. If a macroscopic lesion is not detectable and the patient has a high-grade tumor that will necessitate an adjuvant therapy, 3 to 5 samples seem sufficient for staging. Further studies are needed to determine the optimum sample size for tumors having a low risk of metastasis.

Diffuse fatty infiltration in amyloid goiter.

Presented herein is a case of diffuse fatty infiltration of amyloid goiter in a 58-year-old woman with chronic renal failure. Bilateral total thyroidectomy was performed due to symptoms of dysphagia and hoarseness. Macroscopic and microscopic examination showed that almost all thyroid follicles were replaced by fat cells. Hyalinized stroma intervening the fatty infiltration was shown to harbor amyloid deposition.