Posttransplant lymphoproliferative disorders (PTLDs) represent a spectrum ranging from Epstein-Barr virus (EBV)-driven polyclonal lymphoid proliferations to EBV+ or EBV- malignant lymphomas. Central nervous system (CNS) PTLDs have not been characterized fully. We reviewed the clinical, radiologic, and pathologic features of 12 primary CNS PTLDs to define them more precisely. Patients included 10 males and 2 females (median age, 43.4 years) who were recipients of kidney (n = 5), liver (n = 2), heart (n = 2), peripheral blood stem cells (n = 2), or bone marrow (n = 1). All received immunosuppressive therapy. CNS symptoms developed 3 to 131 months (mean, 31 months) after transplantation. By neuroimaging, most showed multiple (3 to 9) intra-axial, contrast-enhancing lesions. Histologic sections showed marked expansion of perivascular spaces by large, cytologically malignant lymphoid cells that were CD45+, CD20+, EBV+ and showed light chain restriction or immunoglobulin gene rearrangement. In distinction to PTLDs in other organ systems, CNS PTLDs were uniformly high-grade lymphomas that fulfilled the World Health Organization criteria for monomorphic PTLDs. Extremely short survival periods were noted for each CNS PTLD that followed peripheral blood stem cell transplantation. Survival of others with CNS PTLD varied; some lived more than 2 years.

BACKGROUNDA survey of the distribution of human papillomavirus (HPV) types across the spectrum of cervical cytologic categories defined by the Bethesda 2001 guidelines was conducted with the objective of examining how HPV detection by polymerase chain reaction (PCR) analysis may benefit the management of patients who have abnormal Papanicolaou (Pap) test results.METHODSDNA samples from women with no intraepithelial lesion or malignancy (NLM) (n = 300 samples); atypical squamous cells of undetermined significance (ASC‐US) (n = 200 samples); low‐grade squamous intraepithelial lesion (LSIL) (n = 200 samples); atypical squamous cells, cannot rule out high‐grade squamous intraepithelial lesion (ASC‐H) (n = 200 samples); and high‐grade squamous intraepithelial lesion (HSIL) (n = 200 samples) were tested for HPV using a modified general primer (GP)5+/GP6+ PCR assay and dot‐blot hybridization with type‐specific oligonucleotide probes (PCR assay analytical sensitivity: 1–100 copies of HPV, depending on the HPV type, in a background of 100 ng human DNA).RESULTSHPV was detected in 27% of NLM samples, in 89.5% of ASC‐US samples, in 97.5% of LSIL samples, in 93% of ASC‐H samples, and in 96.5% of HSIL samples. Thirty‐seven different HPV types were identified in total. One or more of 13 high‐risk (HR) HPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68) were detected in 53% of samples that were diagnosed as ASC‐US (59.0% of patients younger than age 30 yrs; 45.5% of patients age 30 yrs and older), in 55.5% of samples that were diagnosed as LSIL (60.0% of patients younger than age 30 yrs; 44.0% of patients age 30 yrs and older), in 80% of samples that were diagnosed as ASC‐H, and in 87.5% of samples that were diagnosed as HSIL (P < 0.001). HPV‐16 was detected in 17.5% of ASC‐US samples, in 15.5% of LSIL samples, in 48.5% of ASC‐H samples, and in 49.0% of HSIL samples (P < 0.001). Among abnormal smears, HR HPV was significantly more common in women younger than age 30 years compared with women age 30 years and older (P < 0.002). Follow‐up biopsy data were obtained for 359 patients. A “benign” biopsy result was recorded for 47 of 64 women (73.5%) with ASC‐US, 30 of 66 women (45.5%) with LSIL, 39 of 87 women (45.0%) with ASC‐H, and 26 of 142 women (18.0%) with HSIL and was most common in women age 30 years and older (P < 0.0001). Cervical intraepithelial neoplasia (CIN) Grade I (CIN‐I) was found in 14.0% of women with ASC‐US, in 39.5% of women with LSIL, in 8.0% of women with ASC‐H, and in 7.0% of women with HSIL. CIN‐II was diagnosed in 9.5% of women with ASC‐US, in 13.5% of women with LSIL, in 19.5% of women with ASC‐H, and in 24.0% of women with HSIL. CIN‐III was identified in 2 women (3.0%) with ASC‐US, in 1 woman (1.5%) with LSIL, in 24 women (27.5%) with ASC‐H, and in 71 women (50.0%) with HSIL.CONCLUSIONSHR HPV testing by PCR of samples diagnosed according to the Bethesda 2001 guidelines may benefit the management of patients with ASC‐US or patients with LSIL, especially among women age 30 years and older, by allowing exclusion from referral for biopsy of women who are negative for HR HPV types. However, the small numbers of women who had CIN‐III detected after a diagnosis of ASC‐US or LSIL limited the assessment of test sensitivity. Cancer 2006. © 2006 American Cancer Society.

The Cytyc ThinPrep Imaging System was FDA approved based on a multi-institutional clinical trial, in which the HSIL+ prevalence rate was 0.7%. This study determines the effectiveness of the Imager in clinical practice at an academic medical center with a historical HSIL+ rate of 0.25%. Cytological interpretations were compared for two 12-month periods pre- and post-Imager implementation. Data was compiled by cytologic diagnoses, and variations in prevalence rates were analyzed for statistical significance. Interpretations of ASC-US, ASC-H, and LSIL were correlated with Digene Hybrid Capture2 High Risk HPV DNA testing; interpretations of ASC-H, LSIL, and HSIL+ were correlated with subsequent surgical follow-up. ASC-US, ASC-H, and LSIL detection rates increased 34, 48, and 29%, respectively, with the Imager (P<0.001); whereas the detection of HSIL increased 24% (P<0.051). Surgical correlation revealed no statistical differences in the positive predictive value (PPV) for ASC-H and LSIL. However, an increase in the PPV of HSIL was found (P<0.05). High risk HPV results were lower for ASC-US (P<0.001), but statistically equivalent for ASC-H and LSIL. Results of surgical correlation and HPV testing validated an increase in detection rates of ASC-H, LSIL, and HSIL, as well as increased PPV of HSIL with the ThinPrep Imaging System.