Valeria Ascoli

Q-elastography in the presurgical diagnosis of thyroid nodules with indeterminate cytology.

Quantitative ultrasound (US) elastography (Q-USE), able to evaluate tissue stiffness has been indicated as a new diagnostic tool to differentiate benign from malignant thyroid lesions. Aim of this prospective study, conducted at the Department of Surgical Sciences, of the “Sapienza” University of Rome, was to evaluate the diagnostic accuracy of Q-USE, compared with US parameters, in thyroid nodules with indeterminate cytology (Thy3).The case study included 140 nodules from 140 consecutive patients. Patient’s thyroid nodules were evaluated by Q-USE, measuring the strain ratio (SR) of stiffness between nodular and surrounding normal thyroid tissue, and conventional US parameters prior fine-needle aspiration cytology. Those with Thy3 diagnosis were included in the study. Forty of the nodules analyzed harbored a malignant lesion. Q-USE demonstrated that malignant nodules have a significant higher stiffness with respect to benign one and an optimun SR cut-off value of 2.05 was individuated following ROC analysis. Univariate analysis showed that hypoechogenicity, irregular margins and SR >2.05 associated with malignancy, with an accuracy of 67.2%, 81,0% and 89.8%, respectively. Data were unaffected by nodule size or thyroiditis. These findings were confirmed in multivariate analysis demonstrating a significant association of the SR and the irregular margins with thyroid nodule’s malignancy. In conclusion, we demonstrated the diagnostic utility of Q-USE in the differential diagnosis of thyroid nodules with indeterminate cytology that, if confirmed, could be of major clinical utility in patients’ presurgical selection.

Primary effusion Burkitt's lymphoma with t(8;22) in a patient with hepatitis C virus related cirrhosis

Hepatitis C virus (HCV) infection may be complicated by non-Hodgkins lymphoma through yet unknown pathogenetic mechanisms. We describe the case of a patient with HCV-related cirrhosis who developed a primary effusion lymphoma (PEL) of Burkitts type confined to the peritoneal cavity, in the absence of immunodeficiency or autoimmunity. Paracentesis followed by immunophenotyping, karyotyping, and molecular studies allowed us to diagnose a small noncleaved B-cell lymphoma (CD20+, CD24+, CD10+, CD5-, CD23-, lambda+) with the t(8;22) (q24;q11) translocation and clonal rearrangement of the immunoglobulin heavy chain gene. HCV-RNA, Epstein-Barr virus and Kaposis sarcoma-associated herpesvirus were not identified within lymphoma cells. The finding of HCV-RNA in the ascitic fluid suggests a link between HCV and development of lymphoma with HCV playing the role of persistent antigenic stimulation to intraperitoneal B-cell clonal expansion(s).

Human herpes virus-8 associated primary effusion lymphoma of the pleural cavity in HIV-negative elderly men

Human herpes virus-8 (HHV-8)-associated primary effusion lymphoma (PEL) is an unusual lymphoma confined to the body cavities, which primarily affects human immunodeficiency virus (HIV)-positive men at high risk for Kaposis sarcoma (KS). We describe two HIV-negative elderly Italian men, who developed pleural HHV-8-positive PEL in association with other diseases (systemic hypertension, colonic carcinoma, chronic obstructive airways disease, dilated cardiomyopathy), but without KS. Thoracic computed tomography revealed unilateral pleural effusion and pleural thickening. Thoracentesis disclosed large lymphoma cells, with no T- or B-cell associated antigens, clonal rearrangement of the immunoglobulin heavy chain gene and the presence of HHV-8 but not Epstein-Barr virus deoxyribonucleic acid sequences. Our cases differ from most pleural effusion lymphomas, in that they are non-acquired immunodeficiency syndrome-related. This highlights the possible human herpes virus-8-associated primary effusion lymphoma risk among elderly human immunodeficiency virus-negative patients, particularly Italians, in whom human herpes virus-8 seroprevalence rates and incidence of classic Kaposis sarcoma are high.

Primary effusion lymphoma in HIV-infected patients with multicentric Castleman's disease

Multicentric Castlemans disease (MCD) and primary effusion lymphoma (PEL) are two B‐cell lymphoproliferative diseases associated with Kaposis sarcoma‐associated herpes virus/human herpesvirus‐8 (KSHV/HHV‐8). Although MCD is considered a prelymphoma state, it is not known whether a pathogenetic link exists between MCD and PEL. This paper reports the clinico‐pathological features of four cases of PEL (two pericardial, one pleural, and one peritoneal) developing in the context of HIV‐associated MCD. Effusions, lymph nodes, spleen, and additional tissues from three autopsies were examined for morphology/immunophenotype, search for HHV‐8 DNA, and assessment of immunoglobulin heavy chain gene (IgH) configuration using polymerase chain reaction (PCR)‐based techniques. MCD and PEL samples contained HHV‐8 DNA. Clonal IgH rearrangements were detected only in PEL, whereas MCD tissues were polyclonal. Light‐chain immunostaining confirmed B‐cell clonality in PEL (two lambda, one kappa, one not tested) and polyclonality in MCD. The autopsies revealed different morphological variants of visceral KS and multi‐organ atypical infiltrates exhibiting immunoblastic/plasmablastic features reminiscent of PEL morphology, with a restriction of lambda‐positive cells. In two cases, using microdissection and IgH PCR analysis, multiple/discrete bands were found in the infiltrates, compatible with polyclonality/oligoclonality. The case showing an oligoclonal IgH ladder contained a rearrangement of identical junctional size to the PEL clone; however, further analysis with PEL‐derived clonotypic primers and sequencing of PCR products showed no amplification and nucleotide diversity, respectively, indicating that the two B‐cell populations examined were clonally unrelated. These data show that MCD and PEL may co‐exist in HIV‐infected patients, suggesting a relevant association between these two HHV‐8‐related disorders. Although a definite clonal relationship between MCD and PEL was not demonstrated, it is hypothesized that in some MCD cases, within expanded polyclonal B‐cell populations secondary to HHV‐8 infection, clonal expansions may occur that localize into a body cavity, i.e. PEL. Copyright

Risk of soft tissue sarcomas and residence in the neighbourhood of an incinerator of industrial wastes.

Aims: To investigate the association between occurrence of soft tissue sarcomas (STS) in Mantua and residence near an incinerator of industrial wastes. Methods: Cases were subjects with histologically confirmed primary malignant STS diagnosed 1989–98 in the population resident in Mantua and in the three neighbouring municipalities. Controls were randomly extracted from population registries, matched for age and sex. Residential history was reconstructed for all study subjects since 1960. Main residence was geographically positioned according to GPS standards. Results: The study included 37 STS cases (17 men and 20 women) and 171 controls. The incidence of STS in the area of study was estimated as 8.8 per 100 000 in men and 5.6 per 100 000 in women. The odds ratio associated with residence within 2 km, standardised by age and sex, was 31.4 (95% CI 5.6 to 176.1), based on five exposed cases. At greater distances, risk rapidly decreased, showing a fluctuation around the null value of 1. Conclusion: The study shows a significant increase in risk of STS associated with residence within 2 km of an industrial waste incinerator; an aetiological role of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can be hypothesised.

DNA copy number changes in familial malignant mesothelioma

Malignant mesothelioma (MM) is predominantly a sporadic malignancy linked to exposure to asbestos. Clustering of MM in families suggests genetic susceptibility as a contributing factor. We performed comparative genomic hybridization (CGH) analysis on tumor samples from members of a family with MM of the pleura and a history of parental cancer. Our specific aim was to find a recurrent copy number loss indicating the chromosomal area to which a gene underlying the development of MM could be assigned according to the Knudson two-hit hypothesis. We found losses at 1p, 6q, 9p, 13q, and 14q. The copy number changes were very similar to those reported in sporadic cases. Our findings and results from sporadic cases highlight the importance of cloning the genes in the loss sites at 1p, 6q, 14q, and 22q.

Reduced seroprevalence of Kaposi's sarcoma-associated herpesvirus (KSHV), human herpesvirus 8 (HHV8), related to suppression of Anopheles density in Italy

Abstract.  In two formerly malarious parts of Italy, age‐related seroprevalence rates of Kaposis sarcoma‐associated herpesvirus [human herpesvirus 8 (KSHV/HHV8)] were determined from local blood donors and correlated with periods of vector control during anti‐malaria campaigns. In Veneto, decreased KSHV/HHV8 seroprevalence in the 1951–1955 birth cohort coincides with the peak of DDT house‐spraying. In Sardinia, where larviciding augmented indoor DDT‐spraying, a significant drop of KSHV/HHV8 seroprevalence between 1945 and 1950 and 1951–1955 birth cohorts (P = 0.0046) coincides with suppression of the malaria vector Anopheles labranchiae Falleroni (Diptera: Culicidae). These results are consistent with age‐related association between KSHV/HHV8 seroprevalence rates in native/resident populations and the density of malaria vectors in Veneto and Sardinia. This example supports our ‘promoter arthropod’ hypothesis on the role of haematophagous insects [putatively blackflies (Simuliidae), sandflies (Phlebotominae) and biting midges (Ceratopogonidae), as well as mosquitoes] when their bites induce hypersensitivity and immunosuppression, potentiate KSHV/HHV8 transmission via human saliva (when insect bite lesions are licked by another person whose saliva carries the virus) and may facilitate Kaposis sarcoma.

Guidelines for cytopathologic diagnosis of epithelioid and mixed type malignant mesothelioma. Complementary statement from the International Mesothelioma Interest Group, also endorsed by the International Academy of Cytology and the Papanicolaou Society of Cytopathology.

To provide practical guidelines for the cytopathologic diagnosis of malignant mesothelioma (MM). Cytopathologists involved in the International Mesothelioma Interest Group (IMIG) and the International Academy of Cytology (IAC), who have an interest in the field contributed to this update. Reference material includes peer-reviewed publications and textbooks. This article is the result of discussions during and after the IMIG 2012 conference in Boston, followed by thorough discussions during the 2013 IAC meeting in Paris. Additional contributions have been obtained from cytopathologists and scientists, who could not attend these meetings, with final discussions and input during the IMIG 2014 conference in cape town. During the previous IMIG biennial meetings, thorough discussions have resulted in published guidelines for the pathologic diagnosis of MM. However, previous recommendations have stated that the diagnosis of MM should be based on histological material only.[12] Accumulating evidence now indicates that the cytological diagnosis of MM supported by ancillary techniques is as reliable as that based on histopathology, although the sensitivity with cytology may be somewhat lower.[345] Recognizing that noninvasive diagnostic modalities benefit both the patient and the health system, future recommendations should include cytology as an accepted method for the diagnosis of this malignancy.[67] The article describes the consensus of opinions of the authors on how cytology together with ancillary testing can be used to establish a reliable diagnosis of MM.

Body cavity lymphoma.

Body cavity lymphomas (BCLs) are a heterogeneous group of rare, primary non-Hodgkins lymphomas that proliferate within the serous body cavities and result in recurrent effusions. This review is mainly focussed on the distinct entity primary effusion lymphoma (PEL) wherein the tumor clone is infected by human herpesvirus-8, the etiologic agent of Kaposis sarcoma. In addition, we briefly discuss here recent data regarding other BCL types. The latter include a subset with no evidence of herpesvirus 8 which is associated with Epstein-Barr virus (pyothorax-associated lymphoma, PAL), the BCL forms associated to hepatitis C virus-related cirrhosis or alcohol-related cirrhosis and, finally, non-neoplastic forms mimicking lymphomatous effusions.

Human herpesvirus-8 in lymphomatous and nonlymphomatous body cavity effusions developing in Kaposi's sarcoma and multicentric Castleman's disease

Human herpesvirus-8 (HHV-8) has been associated with Kaposis sarcoma, multicentric Castlemans disease and primary effusion lymphoma. Kaposis sarcoma and multicentric Castlemans disease patients may develop body cavity effusions that, unlike primary effusion lymphoma, are poorly characterized. To better define these effusions, pleural and peritoneal fluids derived from 12 human immunodeficiency virus-seropositive and one seronegative patients affected by Kaposis sarcoma or multicentric Castlemans disease were analyzed by a combination of morphologic, immunophenotypic, and DNA analyses, including polymerase chain reaction amplification of HHV-8, Epstein-Barr virus, and immunoglobulin heavy-chain (IgH) gene sequences. In addition, HHV-8 serologic status was assessed by using an immunofluorescence assay. All patients were adult men with high antibody titers to HHV-8; 11 of the 13 patients were homosexual/bisexual. Effusions revealed monocyte/macrophage-rich infiltration (10 patients) or large-cell lymphoma with CD45(+)/non-T/non-B phenotype (three of 13 patients); polymerase chain reaction analysis showed the presence of HHV-8 sequences (nine of 13 patients), germline IgH (seven of 12 patients) or clonal IgH rearrangements (four of 12 patients), and rarely Epstein-Barr virus sequences (two of 12 patients). In the setting of HHV-8 infection, two effusion types may occur. One fulfills the criteria for HHV-8-positive PEL (lymphoma-morphology, HHV-8-DNA(+), IgH rearrangement). The other seems more reminiscent of an HHV-8-associated nonneoplastic process (monocyte-macrophage morphology, HHV-8-DNA(+/-), germline IgH). Interestingly, a single case of the latter effusion type harbored a B-cell monoclonal proliferation, which suggests the hypothesis that a prelymphomatous effusion may precede overt body cavity lymphoma.