Circulating Exosomal miR-1290 for Diagnosis of Epithelial Ovarian Cancer

The aim of the study was to develop a new diagnostic biomarker for identifying serum exosomal miRNAs specific to epithelial ovarian cancer (EOC) and to find out target gene of the miRNA for exploring the molecular mechanisms in EOC. A total of 84 cases of ovarian masses and sera were enrolled, comprising EOC (n = 71), benign ovarian neoplasms (n = 13). We detected expression of candidate miRNAs in the serum and tissue of both benign ovarian neoplasm group and EOC group using real-time polymerase chain reaction. Immunohistochemistry were constructed using formalin fixed paraffin embedded (FFPE) tissue to detect expression level of suppressor of cytokine signaling 4 (SOCS4). In the EOC group, miRNA-1290 was significantly overexpressed in serum exosomes and tissues as compared to benign ovarian neoplasm group (fold change ≥ 2, p < 0.05). We observed area under the receiver operating characteristic curve (AUC) for miR-1290, using a cut-off of 0.73, the exosomal miR-1290 from serum had AUC, sensitivity, and specificity values of 0.794, 69.2 and 87.3, respectively. In immunohistochemical study, expression of SOCS4 in EOC was lower than that in benign ovarian neoplasm. Serum exosomal miR-1290 could be considered as a biomarker for differential diagnosis of EOC from benign ovarian neoplasm and SOCS4 might be potential target gene of miR-1290 in EOC.     

Presence of Human Papillomavirus DNA in Malignant Neoplasia and Non-Malignant Breast Disease

Breast cancer is the leading cause of cancer death among women worldwide. Multiple extrinsic and intrinsic factors are associated with this disease’s development. Various research groups worldwide have reported the presence of human papillomavirus (HPV) DNA in samples of malignant breast tumors. Although its role in mammary carcinogenesis is not fully understood, it is known that the HPV genome, once inserted into host cells, has oncogenic capabilities. The present study aimed to detect the presence of HPV DNA in 116 breast tissue biopsies and classify them according to their histology. It was found that 50.9% of the breast biopsies analyzed were malignant neoplasms, of which 74.6% were histologically classified as infiltrating ductal carcinoma. In biopsies with non-malignant breast disease, fibroadenoma was the most common benign neoplasm (39.1%). Detection of HPV DNA was performed through nested PCR using the external primer MY09/11 and the internal primer GP5+/6+. A hybridization assay genotyped HPV. HPV DNA was identified in 20.3% (12/59) of malignant neoplasms and 35% non-malignant breast disease (16/46). It was also detected in 27.3% (3/11) of breast tissue biopsies without alteration. However, there are no statistically significant differences between these groups and the existence of HPV DNA (p = 0.2521). Its presence was more frequent in non-malignant alterations than in malignant neoplasias. The most frequent genotypes in the HPV-positive samples were low-risk (LR) HPV-42 followed by high-risk (HR) HPV-31.     

Spectrum and Risk of Neoplasia in Werner Syndrome: A Systematic Review

Background

Werner syndrome (WS) is an autosomal recessive genetic instability and progeroid (‘premature aging’) syndrome which is associated with an elevated risk of cancer.

Objectives

Our study objectives were to characterize the spectrum of neoplasia in WS using a well-documented study population, and to estimate the type-specific risk of neoplasia in WS relative to the general population.

Methods

We obtained case reports of neoplasms in WS patients through examining previous case series and reviews of WS, as well as through database searching in PubMed, Google Scholar, and J-EAST, a search engine for articles from Japan. We defined the spectrum (types and sites) of neoplasia in WS using all case reports, and were able to determine neoplasm type-specific risk in Japan WS patients by calculating standardized incidence and proportionate incidence ratios (SIR and SPIR, respectively) relative to Osaka Japan prefecture incidence rates.

Results

We used a newly assembled study population of 189 WS patients with 248 neoplasms to define the spectrum of neoplasia in WS. The most frequent neoplasms in WS patients, representing 2/3 of all reports, were thyroid neoplasms, malignant melanoma, meningioma, soft tissue sarcomas, leukemia and pre-leukemic conditions of the bone marrow, and primary bone neoplasms. Cancer risk defined by SIRs was significantly elevated in Japan-resident WS patients for the six most frequent neoplasms except leukemia, ranging from 53.5-fold for melanoma of the skin (95% CI: 24.5, 101.6) to 8.9 (95% CI: 4.9, 15.0) for thyroid neoplasms. Cancer risk as defined by SPIR was also significantly elevated for the most common malignancies except leukemia.

Conclusions

WS confers a strong predisposition to several specific types of neoplasia. These results serve as a guide for WS clinical care, and for additional analyses to define the mechanistic basis for cancer in WS and the general population.     

Comparison of diagnostic results obtained by fine needle aspiration cytology and tru-cut or open biopsies

In seven cases fine needle aspiration (FNA) cytology provided a diagnosis of neoplasm when the Tru-Cut (TC) tissue biopsies (four cases) and open biopsies (three cases) were negative. The specimens consisted of two breast carcinomas, two metastatic neoplasms in the liver, one metastatic melanoma in inguinal lymph nodes, a retroperitoneal mass and a pelvic mass. In the two cases of mammary carcinoma, TC biopsies were negative and FNAs were diagnostic of carcinoma. TC biopsies in the two cases of questionable hepatic metastasis were negative, but FNAs demonstrated a malignant neoplasm. Open biopsy of a retroperitoneal mass failed to diagnose a neoplasm however, subsequent ultrasound-directed FNA demonstrated a neoplasm, possibly seminoma. FNA cytology of inguinal lymph nodes in one case was diagnostic of melanoma; open biopsy showed no neoplasm. Because of the FNA diagnosis, additional sections were made and the presence of melanoma was confirmed. This series demonstrates that FNA cytology should be considered the initial diagnostic procedure more often.     

Immunohistochemical evaluation of ras oncogene expression in pulmonary and pleural neoplasms

We undertook an immunohistochemical analysis of human bronchopulmonary epithelial neoplasms and pleural mesotheliomas using a monoclonal antibody which recognizes ras oncogene products (p21ras). The monoclonal antibody, RAP-5, recognizes both unaltered and certain mutated p21ras. Formalin fixed and paraffin embedded tissue samples of 187 lung epithelial tumors and 27 pleural mesotheliomas were investigated; normal and bronchiectatic lungs were similarly studied. Normal lung and pleural tissue did not immunostain except for occasional type II pneumocytes. Reactive type II pneumocytes adjacent to carcinomas and bronchiectasis immunostained consistently. Twenty four/34 (71%) squamous carcinomas immunostained. Only 8/50 (16%) adenocarcinomas immunostained focally and weakly whereas 19/24 (79%) bronchioloalveolar carcinomas immunostained. Eleven/18 (61%) large cell carcinomas immunostained with variable intensity. Eleven/13 (85%) carcinoids, 6/7 (85%) well differentiated neuroendocrine carcinomas, and 18/21 (86%) intermediate cell neuroendocrine carcinomas immunostained while none of 20 small cell neuroendocrine carcinomas immunostained. Only a few mesotheliomas were immunostained focally. Two/14 (14%) epithelial type and 1/9 (11%) biphasic type mesotheliomas immunostained weakly; none of 4 spindle cell mesotheliomas immunostained. We conclude that while at least occasional cases of most types of pulmonary epithelial neoplasms express p21ras, the frequency and intensity of the expression are distinctly greater in certain tumor types such as squamous, bronchioloalveolar, and neuroendocrine neoplasm except for the small cell type. Contrary to these lung epithelial neoplasms, most mesotheliomas did not immunostain for p21ras. Whether the enhanced p21ras expression may point to a different mechanism of transformation or may merely reflect differentiation features remains undetermined.     

Accuracy of blood cytological screening techniques for the diagnosis of a possible hematopoietic neoplasm in the bivalve mollusc,Mya arenaria

The two in vivo bleeding techniques currently in use in our laboratory to diagnose a hematopoietic neoplasm in Mya arenaria are: (1) phase-contrast microscopy with fresh unstained hemocytes, and (2) bright-field microscopy with Giemsa-stained hemocytes. All in vivo diagnoses were checked by histopathological studies on tissues of the same mollusc. For both methods the correct diagnosis (true + or true ?) was made in 94 out of 100 clams examined. A gradation of tissue involvement was observed in the diseased clams and the accuracy of the in vivo diagnosis is related to the disease severity. There is a positive correlation between the degree of tissue involvement and the number of circulating neoplastic cells. For this reason the more extensive the neoplasm the better is the ability to diagnose the neoplasm by the in vivo bleeding techniques. Depending on the percentage of neoplastic cells present in the hemolymph, the neoplasm was graded from level 1 to 5, with 5 being the most severe. In general, at level 1, the accuracy of a single in vivo diagnosis varied from 66 to 71% and at level 2, the accuracy of diagnosis varied from 76 to 93%, while at all other levels the accuracy was 100%. The percentage of diseased clams detected by the in vivo bleeding technique was 89–91% and the percentage of nondiseased clams detected was 95%. These values can be further improved by combining the two tests and/or through multiple bleedings. Between the two types of in vivo tests, the Giemsa-stained hemocytes provided better precision of diagnosis than the fresh unstained cells, although the differences were slight.     

Differentiation of Hashimoto's thyroiditis from thyroid neoplasms in fine needle aspirates

In order to refine the cytodiagnostic criteria for distinguishing Hashimoto's thyroiditis from thyroid neoplasms, aspirates from six cases of Hashimoto's thyroiditis, five Hürthle cell neoplasms and one papillary carcinoma associated with Hashimoto's thyroiditis were reevaluated. Distinguishing characteristics were cell arrangements, nuclear chromatin pattern and nucleolar appearance. Hashimoto's thyroiditis was characterized by flat sheets and clusters of epithelial cells with oncocytic changes or occasionally by cohesive tissue fragments with cells well oriented one to the other. Thyroid neoplasms were characterized by loosely cohesive, syncytial-type tissue fragments with crowded overlapping cells poorly oriented one to the other and/or numerous isolated single cells. The nuclear chromatin of Askanazy cells in Hashimoto's thyroiditis was bland and even while that of neoplastic cells was finely granular, coarsely granular or irregularly clumped. Macronucleoli were present in Hürthle cell tumors but not in the Askanazy cells of Hashimoto's thyroiditis. Epithelial cellularity, lymphoid cellularity, cellular polymorphism and nuclear pleomorphism were not useful criteria for making the differential diagnosis between the two conditions. An admixture of epithelial cells and lymphoid cells indicated Hashimoto's thyroiditis but was not helpful in ruling out an associated neoplasm.     

Necrosis in thyroid nodules after fine needle aspiration biopsy. Report of two cases

Two cases of infarction of thyroid neoplasms following fine needle aspiration (FNA) biopsy are reported. Histologic study of a 2.5 x 2.5 cm nodule excised 18 days after FNA had diagnosed a Hürthle-cell neoplasm showed mainly necrotic debris and granulation tissue. While FNA made the diagnosis of a papillary carcinoma in the second case, which had had an FNA biopsy of the same nodule six years earlier, most of the nodule was fibrotic and necrotic. These two cases demonstrate the potential problems in such cases: (1) post-FNA infarction may obscure the nature of a cytologically diagnosed neoplasm, making histologic confirmation difficult, and (2) FNA of an infarcted nodule may have difficulties in obtaining diagnostic material, potentially resulting in a false-negative diagnosis. Review of the literature on thyroid infarction shows it to be a rare event, with most reported cases occurring after FNA biopsy of a neoplasm. The finding of necrosis and fibrosis in an aspirate or surgical specimen should thus suggest the presence of a neoplasm.     

Clinical and cytologic features of papillary neoplasms of the breast

OBJECTIVE: To compare the cytologic features benign and malignant papillary breast lesions. STUDY DESIGN: We reviewed the clinical and cytologic features in 29 cases of intraductal papilloma and 26 cases of atypical papilloma or papillary carcinoma that had been diagnosed by histologic examination. The diameter of the mass was examined as a clinical feature. The cytologic features evaluated were as follows: bloody background, row of tall columnar cells, naked bipolar nuclei, hemosiderin-laden macrophages, myoepithelial cells, single scattered atypical cells, cellularity, nuclear atypia, nuclear grade, apocrine metaplasia, eosinophilic cytoplasmic granules, papillary clusters, small papillae, cell balls and large sheets. RESULTS: Of the features evaluated, the diameter of the mass, naked bipolar nuclei and cell balls differed significantly between benign and atypical or malignant papillary neoplasms. The average diameter of a benign papillary neoplasm was 1.8 cm, and that of an atypical or malignant papillary neoplasm was 2.2 cm (p = 0.042). Naked bipolar nuclei were found in 27 cases of benign papillary neoplasm (93.1%) versus 19 cases of atypical or malignant papillary neoplasm (73.1%) (p = 0.050). Cell balls were found in 14 (48.3%) and 21 (80.8%) cases, respectively (p = 0.012). All 6 cases in which cell balls were present and naked bipolar nuclei were absent proved to be atypical or malignant papillary neoplasms. Of 17 cases in which cell balls were absent and naked bipolar nuclei present, 13 (76.5%) were benign papillary neoplasms. CONCLUSION: Most cytologic features overlapped in benign and atypical or malignant papillary neoplasms. Although they were not pathognomonic, naked bipolar nuclei and cell balls were cytologic features that differed significantly between benign and atypical or malignant papillary neoplasms. When papillary neoplasms of the breast are suspected in a cytologic smear, the combination of clinical examination, mammography and cytologic features should be considered to make the correct diagnosis.     

CONCENTRIC LAMINATION OF GLIAL PROCESSES IN OLIGODENDROGLIOMAS

Tissues were obtained by open biopsy of a series of human intracranial neoplasms, fixed in Veronal-buffered osmium tetroxide, and embedded in Vestopal-W. In two instances in which specimens were obtained from oligodendrogliomas in regions where the tumor had infiltrated but not entirely destroyed cortical tissues, glial processes were found to be arranged in a highly organized laminar fashion. This feature was not observed in two additional oligodendrogliomas nor in other types of intracerebral neoplasms. Three types of laminar structures were recognized: (a) perikaryal sheaths composed of several layers of overlapping or concentrically orientated glial processes, (b) layers of longitudinally orientated glial processes along the outer aspect of myelinated axons, and (c) small laminated figures composed of several concentrically disposed glial processes. Spirally constituted lamellar systems were not demonstrated. These findings indicate that under certain circumstances glial cells have the capacity to form sheaths and sheath-like structures by concentric lamination of several processes, rather than by spiraling of a single process.     

Proteomic study identified HSP 70 kDa protein 1A as a possible therapeutic target, in combination with histone deacetylase inhibitors, for lymphoid neoplasms

Histone deacetylase inhibitors (HDACi) demonstrate possible anticancer activities in various malignancies including lymphoid neoplasms. However, the anticancer effects of HDACi are often limited, and combination therapy with other drugs has been undertaken to improve the outcome of patients. Here we conducted proteomic investigation of 33 lymphoid cell lines to identify novel therapeutic targets for enhancing the effects of HDACi. Using the proteomic data in our published 2D-DIGE database, we examined the proteins associated with resistance to valproic acid (VPA). The lymphoid neoplasm cell lines in the database were grouped according to their sensitivity to VPA treatment. A comparative proteomic study of the cell line groups resulted in the identification of 10 protein spots, whose intensity was associated with chemosensitivity. Among the identified proteins, HSPA1A showed higher expression in cell lines with resistance to VPA, and the results were validated by Western blotting. In vitro experiments demonstrated that treatment with KNK-437, an inhibitor of HSPA1A, enhanced the cytotoxic effects of VPA, as well as vorinostat, in the lymphoid neoplasm cell line. Treatment with KNK-437 facilitated the apoptotic effects of VPA. In conclusion, we identified HSPA1A as a possible therapeutic target, in combination with HDACi, for lymphoid neoplasms.     

Fine needle aspiration cytology of atypical carcinoid of the lung

The cytologic features of eight atypical carcinoid tumors of the lung, as observed in fine needle aspiration (FNA) specimens, are described in detail. They were compared with 21 pulmonary squamous-cell carcinomas, 16 adenocarcinomas, 5 small-cell undifferentiated carcinomas, 3 large-cell undifferentiated carcinomas and 1 typical carcinoid tumor. Atypical carcinoid tumor was easily distinguished from the other pulmonary neoplasms in most instances. Only two poorly differentiated squamous-cell carcinomas (one of which had atypical carcinoid as a component) and one small-cell undifferentiated carcinoma had similar cytologic features. One atypical carcinoid also had cytologic features similar to small-cell undifferentiated carcinoma. Because atypical carcinoid and small-cell undifferentiated carcinoma, at times, may be difficult to separate in FNA specimens, surgical resection of all stage I neoplasms with cytologic features evocative of either neoplasm is recommended.     

Fine needle aspiration biopsy of well-differentiated liposarcoma of the neck in a young female. A case report.

BACKGROUND: Well-differentiated liposarcomas are low grade, nonmetastasizing, malignant neoplasms composed primarily of mature adipose tissue. They are uncommon in the head and neck. CASE: A 24-year-old female presented to the ears, nose and throat clinic for evaluation of a recent, rapidly growing neck mass on the right side. Fine needle aspiration (FNA) biopsy of the mass showed that the smears had fragments of connective tissue with a mixture of mature-appearing fat traversed by bands of fibrous collagen and vessels. Nuclei within the fat and fibrous bands were mildly irregular, hyperchromatic and enlarged, with one or two small nucleoli. Infrequently present but readily identified, lipoblasts were scattered throughout the aspirate smears. A diagnosis of "atypical lipomatous neoplasm" was rendered. Subsequently, the mass was surgically removed. On histologic examination, the tumor was a well-differentiated liposarcoma. CONCLUSION: FNA biopsy of well-differentiated liposarcomas in the head and neck can present difficulties in the classification and diagnosis of this neoplasm.     

Second malignant neoplasms after cancer in childhood or adolescence. Nordic Society of Paediatric Haematology and Oncology Association of the Nordic Cancer Registries.

OBJECTIVE--To assess the relative risk of developing a second malignant neoplasm in people with a diagnosis of cancer in childhood and adolescence. DESIGN--Register based follow up study. SETTING--Populations of Nordic countries. SUBJECTS--30,880 people under the age of 20 with a first malignant neoplasm diagnosed during the period 1943-87. MAIN OUTCOME MEASURES--Relative and attributable risks of second malignant neoplasms by type of first cancer, age at first diagnosis, calendar period, sex, and country. Expected figures were based on the appropriate national incidence rates for cancer. RESULTS--247 cases of second malignant neoplasms were observed in 238 patients, yielding a relative risk for cancer of 3.6 (95% confidence interval 3.1 to 4.1). The risk changed significantly from 2.6 in people first diagnosed during the 1940s and 1950s to 6.9 among cohort members included in the late 1970s and 1980s. Increases were observed for most types of cancer. Highest levels of the relative risk were seen during the 10 years immediately after first malignant diagnosis. The incidence of second malignant neoplasms attributable to the first cancer and associated treatments, however, showed a consistent rise throughout the 45 years of follow up. CONCLUSION--The estimated risks for a second malignant neoplasm were significantly lower than those found in most large hospital based studies but compatible with the results from a similar population based study in the United Kingdom. Extent of risk and cancer pattern were similar among the Nordic countries and are believed to be representative for a large part of the European population.     

Development Capacities of Mixed Normal and Neoplastic 1(3)gl Imaginal Discs and Neuroblast Tissue in Drosophila hydei

The pleiotropic mutant lethal(3)giant larvae [l(3)gl] of Drosophila hydei exhibits among other anatomical defects, hypertrophy of the larval brain and imaginal discs. Both hypertrophic tissues when transplanted into wild-type female flies behave as fast growing and lethal neoplasms. Implanted into mature wild-type larvae they fail to metamorphose. When l(3)gl neoplastic brain tissue or imaginal discs were mixed with normal imaginal discs, cultured in vivo in the abdomen of adult females and transplanted into mature wild-type larvae, the following results were obtained. The invasive l(3)gl brain neoplasm, while fatal for adult hosts, had no effect on the metamorphosis of normal imaginal disc tissue. On the other hand, the noninvasive l(3)gl imaginal disc neoplasms when mixed with normal imaginal disc tissue inhibited its development and metamorphosis in the wild-type host. This inhibitory effect was not observed when the tissues were injected as separate implants into the same host.     

"Collagen balls" in peritoneal washings. Prevalence, morphology, origin and significance.

Peritoneal washings obtained at laparotomy from women undergoing surgery for neoplasms of the genital tract may contain "collagen balls," consisting of tissue fragments composed of collagen covered with mesothelial cells. Collagen balls were found in 19 (4.5%) of 418 peritoneal washings and were more prevalent in specimens labeled pelvic washings (17 of 294, or 5.8%) than in those labeled peritoneal washings (2 of 124, or 1.6%). In 15 of the 19 cases in which we found collagen balls, at least one ovary was available for microscopic examination. In 14 of the 15 cases minute nodular papillary stromal projections covered with mesothelium were found on the surface of the ovaries. We conclude that collagen balls, a nonspecific entity, most probably originate on the surface of the ovaries. Their significance lies in their being mistaken for mucin-distended cells exfoliated from a neoplasm or from detached fragments of a papillary ovarian neoplasm.     

A clinical analysis of nine new pediatric and adolescent cases of benign minor salivary gland neoplasms and a review of the literature

ABSTRACT: INTRODUCTION: Minor salivary gland neoplasms of epithelial origin are rare in children and adolescents and most are not well documented, except for a few small series and case reports. This study represents a retrospective clinical analysis of nine cases of benign epithelial salivary gland neoplasms accessioned over a 35-year period at the Louisiana State University School of Dentistry and combines the data with well-documented cases from the English-language literature. METHODS: A retrospective clinical analysis of nine cases of benign epithelial salivary gland neoplasms was performed over a 35-year period at the Louisiana State University School of Dentistry and combined with data of well-documented cases from the English-language literature. RESULTS: The nine benign salivary gland neoplasms in patients aged 19 months to 18 years accounted for 2.3% of the Louisiana State University School of Dentistry accessioned salivary gland tumors. These nine cases comprised eight pleomorphic adenomas and one cystadenoma. There were 40 cases in the literature, of which 34 were pleomorphic adenomas. Combining the data for the 42 pleomorphic adenomas resulted in a mean age of 12 years with a 2.8:1 female predilection. The hard palate and/or soft palate were the most common site (69.1%). The average duration and size was 2.1 years and 2.4cm, respectively. Bone involvement occurred in seven cases. Wide local excision was the treatment most often employed. Cases followed for two years or more had a recurrence rate of 13.0%. The remaining seven neoplasms in the combined data comprised myoepithelioma, cystadenoma and sialadenoma papilliferum. CONCLUSIONS: A relatively long duration (2 years) of a submucosal mass in a minor salivary gland-bearing area with or without bone involvement occurring in a child or adolescent should raise the question of a possible salivary gland neoplasm. A pleomorphic adenoma is the most common benign salivary gland neoplasm in the first and second decade of life. Complete surgical excision affords the best chance of preventing recurrence for pleomorphic adenomas. The recurrence rate of pleomorphic adenomas with two or more years follow-up is 13.0%. Other types of minor salivary gland neoplasms are exceedingly rare and therefore data is sparse, precluding any valid conclusions.     

Use of Thiopurines and Risk of Colorectal Neoplasia in Patients with Inflammatory Bowel Diseases: A Meta-Analysis

Objective

Inflammatory bowel disease (IBD) is commonly treated with thiopurines such as azathioprine and mercaptopurine for the maintenance of remission. Studies examining chemopreventive of these medications on colorectal neoplasm in IBD patients have yielded conflicting results. We performed a meta-analysis to assess the role of thiopurines for this indication.

Methods

We performed a systematic search of PubMed, Web of Science, EMBASE and Cochrane to identify studies reporting colorectal neoplasm from IBD patients treated with thiopurines and conducted a meta-analysis of pooled relative risk (RR) using the random effects model.

Results

Nine case-control and ten cohort studies fulfilled the inclusion criteria. The use of thiopurines was associated with a statistically significant decreased incidence of colorectal neoplasm (summary RR=0.71, 95% CI=0.54–0.94, p=0.017), even after adjustment for duration and extent of the disease, but there was high heterogeneity among studies (I ²=68.0%, p<0.001). The RR of advanced neoplasm (high-grade dysplasia and cancer) was 0.72 (95%CI=0.50–1.03, p=0.070) and that of cancer was 0.70 (95% CI=0.46–1.09, p=0.111) for thiopurine-treated patients. Heterogeneity of the studies was affected by the sample size (</≥100 cases) and whether the patients had longstanding colitis (≥7 years).

Conclusion

The current meta-analysis revealed that thiopurines had a chemopreventive effect of colorectal neoplasms and a tendency of reducing advanced colorectal neoplasms in IBD. Due to the heterogeneity of included studies, these results should be interpreted with caution.     

Seasonal aspects of sarcomatous neoplasia in Mya arenaria (soft-shell clam) from Long Island Sound

Mya arenaria were collected monthly for 2.5 years from three populations in Long Island Sound. Histopathological examination revealed that 6.1% of the clams from Stonington, Connecticut, 12.9% of the clams from the Saugatuck River, Westport, Connecticut, and 12.7% of those from Old Mill Beach, Westport, also in Connecticut, had sarcomatous neoplasms. This is the first documented account of the occurrence of clam neoplasm in populations from this geographic area. Peak prevalences of 45, 59, and 60%, respectively, were found in clams from the three study sites. The prevalence of neoplasms in clams collected from three epizootic areas showed a pronounced seasonal pattern, with the highest incidences occurring in the late fall-winter of each year studied. The regular, seasonal occurrence of neoplasia in field populations does not support the hypothesis that pollution alone is the cause of the disorder.     

Characterization of Two Novel Gammapapillomaviruses,HPV179 and HPV184, Isolated from Common Warts of a Renal-Transplant Recipient

Gammapapillomavirus (Gamma-PV) is a diverse and rapidly expanding PV-genus, currently consisting of 76 fully characterized human papillomavirus (HPV) types. In this study, DNA genomes of two novel HPV types, HPV179 and HPV184, obtained from two distinct facial verrucae vulgares specimens of a 64 year-old renal-transplant recipient, were fully cloned, sequenced and characterized. HPV179 and HPV184 genomes comprise 7,228-bp and 7,324-bp, respectively, and contain four early (E1, E2, E6 and E7) and two late genes (L1 and L2); the non-coding region is typically positioned between L1 and E6 genes. Phylogenetic analysis of the L1 nucleotide sequence placed both novel types within the Gamma-PV genus: HPV179 was classified as a novel member of species Gamma-15, additionally containing HPV135 and HPV146, while HPV184 was classified as a single member of a novel species Gamma-25. HPV179 and HPV184 type-specific quantitative real-time PCRs were further developed and used in combination with human beta-globin gene quantitative real-time PCR to determine the prevalence and viral load of the novel types in the patient’s facial warts and several follow-up skin specimens, and in a representative collection, a total of 569 samples, of HPV-associated benign and malignant neoplasms, hair follicles and anal and oral mucosa specimens obtained from immunocompetent individuals. HPV179 and HPV184 viral loads in patients’ facial warts were estimated to be 2,463 and 3,200 genome copies per single cell, respectively, suggesting their active role in the development of common warts in organ-transplant recipients. In addition, in this particular patient, both novel types had established a persistent infection of the skin for more than four years. Among immunocompetent individuals, HPV179 was further detected in low-copy numbers in a few skin specimens, indicating its cutaneous tissue tropism, while HPV184 was further detected in low-copy numbers in one mucosal and a few skin specimens, suggesting its dual tissue tropism.