Diagnostic criteria and behavior of ovarian seromucinous (endocervical-type mucinous and mixed cell-type) tumors: atypical proliferative (borderline) tumors,intraepithelial, microinvasive,and invasive carcinomas

Ovarian endocervical-type (müllerian) mucinous tumors and tumors composed of a mixture of endocervical-type mucinous, serous, endometrioid, squamous, and indifferent cells with abundant eosinophilic cytoplasm reported to date have been primarily limited to borderline and microinvasive types, with only one report of a disease-related death. The clinicopathologic features of 54 endocervical-type and mixed cell-type mucinous tumors, defined as tumors with papillary architecture resembling serous tumors but containing endocervical-type mucinous epithelium, were evaluated. Thirty-four tumors (64%) were classified as atypical proliferative (borderline) tumors based on the absence of stromal invasion and the absence of micropapillary architecture measuring >5 mm. Five tumors (9%) qualified as intraepithelial carcinoma based on the presence of marked cytologic atypia or a complex cribriform growth pattern involving the epithelium covering the surface of papillae or lining cystic spaces. Eight tumors (15%) with stromal invasion < or =5 mm were classified as microinvasive carcinoma. Seven tumors (13%) with either stromal invasion (five tumors) or micropapillary architecture measuring >5 mm (two tumors) were classified as carcinoma. Sixteen tumors (30%) were bilateral, and endosalpingiosis was identified in 41% of cases. Serous-type differentiation was present in all cases. Of the 29 patients with atypical proliferative tumors, intraepithelial carcinomas, and microinvasive carcinomas for whom follow-up was available, there were no disease-related deaths. In contrast, of the seven patients whose tumors had either stromal invasion or micropapillary architecture >5 mm, two stage III patients died of disease (one with frank invasion and one with a micropapillary tumor that lacked stromal invasion). One other stage III patient with a noninvasive micropapillary carcinoma was alive with disease at 84 months. The remaining four patients (three stage I and one stage III) were alive with no evidence of disease. In summary, most endocervical-type atypical proliferative tumors are stage I and benign. The presence of either intraepithelial carcinoma or microinvasion has no adverse effect on behavior. Rare endocervical-type mucinous tumors demonstrate histologically malignant features and aggressive behavior that warrant designation as carcinoma. As with serous tumors, micropapillary architecture without frank invasion in endocervical-type mucinous tumors is associated with disease recurrence and death when presenting as advanced-stage disease. All the tumors in this study were composed of a heterogeneous population of cells, consisting mainly of serous (ciliated) and endocervical-type mucinous cells. In addition, they all contained endometrioid-type cells, hobnail cells, and indifferent cells with abundant eosinophilic cytoplasm to a varying degree. Accordingly, it appears that tumors that feature endocervical-type mucinous cells are rarely if ever pure but almost invariably of mixed cell type. Despite containing mucinous epithelium, the papillary architecture, serous-type differentiation, association with endosalpingiosis, frequent bilaterality, size, and clinical behavior of endocervical-type mucinous tumors closely resemble serous tumors. We therefore recommend the term "seromucinous" for these tumors, which acknowledges both their serous and mucinous features.     

Government policies as a threat to health: findings from two Toronto community quality of life studies

Community members, service providers, and elected representatives in two Toronto communities were asked to identify community factors influencing the health of community members. Many of the identified barriers to health related to government policies and actions. Cutbacks in federal transfers to provinces and provincial cutbacks in funding for agencies, reductions in social assistance, ending of new social housing, and other policy changes were seen as negatively impacting the health of the community and its members. These perceptions were remarkably consistent with emerging findings concerning the determinants of health. Implications for public health practice were considered.     

Cervical adenoid basal tumors comprised of adenoid basal epithelioma associated with various types of invasive carcinoma: clinicopathologic features, human papillomavirus DNA detection, and P16 expression

Adenoid basal tumors are uncommon cervical lesions that some pathologists consider invasive carcinomas but others consider "epitheliomas" due to their low-grade histological appearance and rarely documented malignant behavior. We report the clinicopathologic features of 10 tumors comprised of both typical low-grade adenoid basal tumors (epitheliomas) intimately associated with invasive carcinomas having infiltrative growth, increased cytological atypia and mitotic activity, and various types of differentiation, including adenoid basal/squamous, pure squamous, adenoid cystic, and small cell neuroendocrine. Tumors were evaluated for the presence of human papillomavirus (HPV) DNA and immunohistochemical p16 expression. The patients in the study group ranged in age from 45 to 81 years (mean, 65 years). Most of the patients presented with abnormal cervicovaginal smears. The initial diagnosis was made on specimens obtained by cervical biopsy, laser electrocautery excision procedure (LEEP), or cone biopsy in 8 patients. Two 2 patients were incidentally diagnosed in hysterectomy specimens. All 10 patients had squamous intraepithelial lesions (9 high-grade, 1 low-grade). In all cases diagnosed in LEEP or cone biopsy specimens, the invasive carcinoma component was present in the excisional specimen and extended to the margins. Seven patients diagnosed on excisional or biopsy specimens who underwent hysterectomy had residual tumor in the cervix, ranging from microscopic foci to deeply invasive. No lymph node metastases were identified in 4 patients who were staged. Seven patients with follow-up were alive without evidence of disease after follow-up intervals of 8 to 84 months (mean, 45 months; median, 29 months). One patient with a component of small cell carcinoma died of other causes without evidence of disease at 18 months. HPV 16 DNA was detected in both the adenoid basal epithelioma and invasive carcinoma components in 9 tumors by in situ hybridization, and HPV 33 was detected by polymerase chain reaction in 1 tumor. All tumors expressed p16 diffusely. Adenoid basal tumors are high-risk HPV-related tumors that can be comprised of both a low-grade adenoid basal tumor, which can be designated as epithelioma, and invasive carcinomas of various types. The invasive component is usually evident in the excisional biopsy specimen, allowing for recognition of a tumor that needs further management.     

The association between fetal nasal bone hypoplasia and aneuploidy

OBJECTIVE: To determine the association between fetal nasal bone hypoplasia and aneuploidy in women undergoing prenatal diagnosis. METHODS: A prospective cohort study involving women undergoing chorionic villus sampling and amniocentesis for an increased risk of aneuploidy. Fetal biometric and nasal bone measurements were obtained at the time of prenatal diagnosis and compared with karyotypes. Nasal bone hypoplasia was defined as nasal bone less than 2.5th percentile for the gestational age. RESULTS: A total of 632 fetuses were evaluated. Twenty-nine (4.6%) had an aneuploidy (18 trisomy 21, 5 trisomy 18, 1 Turner's syndrome, one Marker chromosome 1, 2 sex chromosome anomalies, and 2 triploidy). Nasal bone measurements were documented in 29 aneuploid fetuses. The nasal bone was either absent or hypoplastic in 12 of 29 (41%) fetuses with aneuploidy and in 8 of 18 (44%) with trisomy 21. By using receiver operating characteristics curves, the optimal threshold of nasal bone hypoplasia associated with fetal aneuploidy was a biparietal diameter/nasal bone ratio of 11 or greater. The sensitivity, specificity, and positive and negative predictive values for the detection of fetal aneuploidy were 50%, 93%, 24%, and 98%, respectively. CONCLUSION: Absent or hypoplastic nasal bone is a marker for fetal aneuploidy in a high-risk population. However, this marker needs to be evaluated by larger prospective studies in low-risk populations before adoption for clinical use.     

Hepatic pathology in human monocytic ehrlichiosis. Ehrlichia chaffeensis infection

Ehrlichia chaffeensis causes human monocytic ehrlichiosis (HME) that usually includes fever, myalgias, and pancytopenia and, in 80% to 90% of patients, elevations in serum transaminase levels. Thus, the pathology of liver injury was studied in liver tissues from 7 patients with laboratory-confirmed HME. H&E and immunohistochemical stains for E chaffeensis and leukocyte markers were examined. Scattered lobular lymphohistiocytic foci and diffuse lymphohistiocytic infiltration and Kupffer cell hyperplasia with increased phagocytosis frequently were present. Various degrees of liver cell injury and death were observed. Cholestasis was evident in 6 cases, sometimes with bile duct epithelial injury. Rare to abundant E chaffeensis-infected mononuclear cells infiltrating lobules or portal regions or in Kupffer cells were observed in 5 patients. The inflammation was out of proportion to the infection in 6 cases. In the absence of infected hepatocytes or biliary epithelial cells, these findings suggest that host inflammatory or immune responses contribute to the liver injury seen in HME.     

Noninvasive and invasive micropapillary (low-grade) serous carcinoma of the ovary: a clinicopathologic analysis of 135 cases

Reports describing the behavior of micropapillary serous carcinomas (MPSCs) of the ovary have focused on those that are noninvasive. There are only very limited data on the behavior of those that are invasive. To further characterize the behavior of MPSCs, invasive versus noninvasive primary tumors were distinguished based on the presence or absence of destructive infiltrative growth. To qualify for inclusion, invasive MPSCs, like the noninvasive tumors, were required to display a micropapillary architecture and low-grade nuclei. A total of 135 cases of MPSC were identified: 96 noninvasive and 39 invasive. On follow-up, survival for 10 patients with stage I noninvasive and invasive MPSCs was 100%, and survival for women with stage II and III noninvasive and invasive MPSCs with noninvasive implants was 80%. In contrast, the 5-year and 10-year survival for patients with stage II and III noninvasive MPSCs with invasive implants was 85% and 55%, respectively. The 5-year and 10-year survival for women with invasive MPSCs and invasive implants was 55% and 45%, respectively. The median time from diagnosis to death for women with noninvasive and invasive MPSCs with invasive implants was 60 months (range 33-240 months). The indolent behavior of these low-grade carcinomas distinguishes them from conventional serous carcinomas, which are high-grade aggressive neoplasms. Five of six patients with small (<5 mm) MPSCs in whom follow-up was available presented with high stage disease. Of these five women, three are alive and well and two are alive with disease (one with invasive and one with noninvasive implants). Nearly three fourths of noninvasive MPSCs were associated with atypical proliferative serous tumors, adenofibromas, or both, and 62% of invasive MPSCs were associated with noninvasive MPSCs, atypical proliferative serous tumors, and adenofibromas, alone or in combination. In addition to the frequent mixtures of these tumor components, transitions between them were common. These data in conjunction with recent molecular genetic studies strongly suggest that MPSCs (low-grade carcinomas) arise from atypical proliferative serous tumors unlike conventional serous carcinomas (high-grade carcinomas), which appear to develop de novo. The findings provide further support for the hypothesis that there are distinct pathways of carcinogenesis for low-grade and high-grade serous carcinoma of the ovary.     

Comparative analysis of sampling methods for grossing radical prostatectomy specimens performed for nonpalpable (stage T1c) prostatic adenocarcinoma

Scant data are available comparing sampling methods of radical prostatectomy specimens performed for clinical stage T1c (nonpalpable) cancer. Seventy-eight stage T1c radical prostatectomies that had 1 or more of the following adverse pathologic findings-Gleason score > or = 7, positive margins, and extraprostatic extension-were compared using 10 different sampling techniques. Of the 78 entirely submitted cases, 52 had Gleason score > or = 7, 14 had positive margins, and 54 had extraprostatic extension (mean 34 slides). Of the partial sampling methods, we favor the following two methods. The first is submitting every posterior section plus 1 midanterior section from right and left sides; if either of these anterior sections show sizeable tumor, all ipsilateral anterior slides are examined. This method detects 98% of tumors with Gleason score > or = 7, 100% of positive margins, and 96% of cases with extraprostatic extension (mean 27 slides). The second method is to use the above method but restrict it to sections ipsilateral to the previous positive needle biopsy. This method detects 92% of tumors with Gleason score > or = 7, 93% of positive margins, and 85% of cases with extraprostatic extension (mean 17 slides). Partial sampling can detect important prognostic parameters. By balancing the extra expense and time involved to process and examine additional sections with the risk of missing important prognostic parameters, pathologists can decide which sampling method to use.     

Problems with proper completion and accuracy of the cause-of-death statement

BACKGROUND: Mortality statistics are largely based on death certificates, so it is important that the data on the death certificate is accurate. At our institution, clinicians complete cause-of-death statements (CODs) prior to autopsy. Since May 1995, separate CODs have been included in autopsy face sheets. METHODS: Clinical and autopsy-based CODs filled out separately on 494 cases between June 1995 and February 1997 were compared for proper reporting and accuracy using the published guidelines and definitions of immediate, intermediate, and underlying causes of death put forth by the College of American Pathologists and the National Center for Health Statistics. RESULTS: Of the 494 death certificates, 204 (41%) contained improperly completed CODs. Of these, 49 (24%) contained major discrepancies between clinicians' and pathologists' CODs. Of the 494 death certificates, 290 (59%) had properly completed CODs. Of the 290 properly completed CODs, 141 (49%) contained disagreements: 73 (52%) on underlying CODs; 44 (31%) on immediate CODs; and 47 (33%) on other significant conditions (part II). CONCLUSIONS: The reliability and accuracy of CODs remain a significant problem. Despite its limitations, the autopsy remains the best standard against which to judge premortem diagnoses. The CODs of the death certificate may be improved if death certificates are completed in conjunction with the postmortem examination and amended when the autopsy findings show a discrepancy.