A Postmortem Portrait of the Coronavirus Disease 2019 (COVID-19) Pandemic: A Large Multi-institutional Autopsy Survey Study.

CONTEXT.­: This study represents the largest compilation to date of clinical and postmortem data from decedents with coronavirus disease 2019 (COVID-19). It will augment previously published small series of autopsy case reports, refine clinicopathologic considerations, and improve the accuracy of future vital statistical reporting. OBJECTIVE.­: To accurately reflect the preexisting diseases and pathologic conditions of decedents with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection through autopsy. DESIGN.­: Comprehensive data from 135 autopsy evaluations of COVID-19-positive decedents is presented, including histologic assessment. Postmortem examinations were performed by 36 pathologists at 19 medical centers or forensic institutions in the United States and Brazil. Data from each autopsy were collected through the online submission of multiple-choice and open-ended survey responses. RESULTS.­: Patients dying of or with COVID-19 had an average of 8.89 pathologic conditions documented at autopsy, spanning a combination of prior chronic disease and acute conditions acquired during hospitalization. Virtually all decedents were cited as having more than 1 preexisting condition, encompassing an average of 2.88 such diseases each. Clinical conditions during terminal hospitalization were cited 395 times for the 135 autopsied decedents and predominantly encompassed acute failure of multiple organ systems and/or impaired coagulation. Myocarditis was rarely cited. CONCLUSIONS.­: Cause-of-death statements in both autopsy reports and death certificates may not encompass the severity or spectrum of comorbid conditions in those dying of or with COVID-19. If supported by additional research, this finding may have implications for public health decisions and reporting moving forward through the pandemic.

Insights into pathogenesis of fatal COVID-19 pneumonia from histopathology with immunohistochemical and viral RNA studies.

INTRODUCTION: We describe post-mortem pulmonary histopathologic findings of COVID-19 pneumonia in patients with a spectrum of disease course, from rapid demise to prolonged hospitalisation. METHODS AND RESULTS: Histopathologic findings in post-mortem lung tissue from eight patients who died from COVID-19 pneumonia were reviewed. Immunohistochemistry (IHC) and next-generation sequencing (NGS) were performed to detect virus. Diffuse alveolar damage (DAD) was seen in all cases with a spectrum of acute phase and/or organising phase. IHC with monoclonal antibodies against SARS-CoV-2 viral nucleoprotein and spike protein detected virus in areas of acute but not organising DAD, with intracellular viral antigen and RNA expression seen predominantly in patients with duration of illness less than 10 days. Major vascular findings included thrombi in medium- and large-calibre vessels, platelet microthrombi detected by CD61 IHC and fibrin microthrombi. CONCLUSIONS: Presence of SARS-CoV-2 viral RNA by NGS early in the disease course and expression of viral antigen by IHC exclusively in the acute, but not in the organising phase of DAD, suggests that the virus may play a major role in initiating the acute lung injury of DAD, but when DAD progresses to the organising phase the virus may have been cleared from the lung by the patient's immune response. These findings suggest the possibility of a major change during the disease course of COVID-19 pneumonia that may have therapeutic implications. Frequent thrombi and microthrombi may also present potential targets for therapeutic intervention.

Double trouble: para-neoplastic anti-PCA-2 and CRMP-5-mediated small fibre neuropathy followed by chorea associated with small cell lung cancer and evolving radiological features.

Patients with Purkinje cell cytoplasmic autoantibody type 2 (PCA-2) and collapsin response-mediator protein-5 (CRMP-5) autoantibody can present with multifocal elements of encephalomyeloneuropathy. Except for an anecdotal report, case descriptions of paraneoplastic small fibre neuropathy are lacking. We report paraneoplastic small fibre neuropathy followed by chorea associated with small cell lung cancer. A man aged 57 years with a 35 pack-year smoking history presented with painless subacute paresthesia and weight fluctuation. A non-length-dependent small fibre neuropathy was confirmed by skin biopsy. Further testing revealed positive serum PCA-2 and CRMP-5 autoantibodies, which after positron emission tomography-CT led to histological confirmation of a small cell lung cancer. Initially, abnormal MRI and cerebrospinal fluid studies suggested central nervous system (CNS) involvement which was subclinical; however, 6 months later during antitumour therapy, the patient became symptomatic with choreoathetosis. After combined chemoradiation as well as immunosuppressive and symptomatic therapies, the clinical course stabilised, although residual neurological deficits remained at follow-up a year later. Coexistent PCA-2 and CRMP-5 autoantibodies may occur in the setting of small fibre peripheral neuropathy and choreoathetosis and predict cancer type. Two paraneoplastic syndromes can present successively over months; subclinical CNS involvement with evolving basal ganglia abnormalities can be a paraneoplastic manifestation. In the appropriate clinical setting, paraneoplastic testing should be considered in patients presenting with small fibre neuropathy.

Primary vaginal mucinous adenocarcinoma of intestinal type, associated with intestinal metaplasia of Skene ducts in a diethylstilbestrol-exposed woman.

OBJECTIVES: Primary mucinous vaginal adenocarcinoma of intestinal type is an extremely rare malignancy of uncertain histogenesis, which makes for a diagnostic challenge. We report a case and describe the histopathologic features and the unusual immunoprofile of this rare entity. METHODS: We report a case of vaginal mucinous adenocarcinoma of intestinal type in a diethylstilbestrol-exposed woman in which intestinal metaplasia of the Skene duct was found at the time of recurrence. RESULTS: As the histogenesis of primary vaginal intestinaltype adenocarcinomas remains uncertain, the finding of Skene duct metaplasia in association with invasive adenocarcinoma lends support to the origin of vaginal mucinous adenocarcinomas of intestinal type to be metaplasia, at least in some cases. Such an origin accounts for the unusual immunohistochemical profile, which raises concern for a metastatic adenocarcinoma of gastrointestinal origin. CONCLUSIONS: Recognition of this rare entity is important, particularly to avoid the pitfall of misdiagnosing metastatic disease.

Increased utilization, verification, and clinical implications of immunocytochemistry: Experience in a northern New England hospital.

BACKGROUND: We report our experience in utilization, verification, and clinical implications of antibodies for use in diagnostic immunocytochemistry (ICC). METHODS: A computer search identified cytology cases utilizing ICC and corresponding surgical pathology material. Alcohol-fixed liquid based cytology (LBC) specimens were generated from surgical pathology bench specimens. ICC on LBC and immunohistochemistry on formalin fixed paraffin embedded tissue (FFPE) were performed in parallel for 71 commonly used antibodies. Cytology and corresponding surgical pathology reports were reviewed for all cases in which antibodies failed verification studies but had been used in the four years prior to implementation of our verification process. RESULTS: From 2007 to 2011, the number of cytology cases in which ICC was performed increased from 98 (or 5% of all non-Pap test/nonurine cytology cases in our laboratory) to 306 (or 15%). Verification studies revealed calretinin, CD5, c-kit/CD117, inhibin, napsin A, OCT 3/4, and PAX-5 to be nonreliable in LBC despite consistent immunoreactivity in concurrent IHC on surgical specimens. No antibodies were found to be immunoreactive on LBC but nonreactive on FFPE. No adverse clinical outcomes resulted from the use of nonverified antibodies. CONCLUSIONS: Utilization of ICC at our institution has increased dramatically in recent years. Our verification process confirmed reliability in the majority of antibodies, but did identify several inconsistent antibodies. Although, in our series, no adverse clinical outcomes resulted from preverification use of these inconsistent antibodies, we encourage other institutions to confirm reliability of antibodies prior to use for diagnostic ICC.

The utility of human papillomavirus testing in young women with atypical glandular cells on pap test.

OBJECTIVE: This study aimed to gain information regarding the follow-up diagnoses and human papillomavirus (HPV) status of women younger than 35 years diagnosed with atypical glandular cells (AGCs) on Pap test. MATERIALS AND METHODS: This is a retrospective observational study in which the cytopathology files at Fletcher Allen Health Care were reviewed from 2000 to 2013 for the diagnoses of AGC in women younger than 35 years. Subsequent pathology reports and HPV testing results were obtained. Significant lesions were defined as cervical intraepithelial neoplasia (CIN) 2 or 3, invasive squamous cell carcinoma, adenocarcinoma in situ, or adenocarcinoma. RESULTS: One hundred six women younger than 35 years with an AGC Pap diagnosis and subsequent follow-up were identified. Significant lesions were diagnosed in 44.3% of the women (47); the majority (55.3%, 26 patients) of which were classified as CIN 2 or 3. Adenocarcinoma in situ was diagnosed in 27.7% of the cases (13). A diagnosis of both CIN 2 or 3 and adenocarcinoma in situ was made in 14.9% of the cases (7). One patient (2.1%) was diagnosed with endometrial adenocarcinoma. The HPV status was identified in 36.8% of the women (39): 69.2% (27) was HPV positive, and 30.8% (12) was HPV negative. Fifty-five percent of HPV-positive women were diagnosed with a significant lesion upon follow-up. No known HPV-negative women were diagnosed with a significant lesion. CONCLUSIONS: Human papillomavirus testing may be useful in risk stratifying young women with AGC on Pap test because they are at risk of having an HPV-positive cervical lesion.

Threonyl-tRNA synthetase overexpression correlates with angiogenic markers and progression of human ovarian cancer.

BACKGROUND: Ovarian tumors create a dynamic microenvironment that promotes angiogenesis and reduces immune responses. Our research has revealed that threonyl-tRNA synthetase (TARS) has an extracellular angiogenic activity separate from its function in protein synthesis. The objective of this study was to test the hypothesis that TARS expression in clinical samples correlates with angiogenic markers and ovarian cancer progression. METHODS: Protein and mRNA databases were explored to correlate TARS expression with ovarian cancer. Serial sections of paraffin embedded ovarian tissues from 70 patients diagnosed with epithelial ovarian cancer and 12 control patients were assessed for expression of TARS, vascular endothelial growth factor (VEGF) and PECAM using immunohistochemistry. TARS secretion from SK-OV-3 human ovarian cancer cells was measured. Serum samples from 31 tissue-matched patients were analyzed by ELISA for TARS, CA-125, and tumor necrosis factor-α (TNF-α). RESULTS: There was a strong association between the tumor expression of TARS and advancing stage of epithelial ovarian cancer (p < 0.001). TARS expression and localization were also correlated with VEGF (p < 0.001). A significant proportion of samples included heavy TARS staining of infiltrating leukocytes which also correlated with stage (p = 0.017). TARS was secreted by ovarian cancer cells, and patient serum TARS was related to tumor TARS and angiogenic markers, but did not achieve significance with respect to stage. Multivariate Cox proportional hazard models revealed a surprising inverse relationship between TARS expression and mortality risk in late stage disease (p = 0.062). CONCLUSIONS: TARS expression is increased in epithelial ovarian cancer and correlates with markers of angiogenic progression. These findings and the association of TARS with disease survival provide clinical validation that TARS is associated with angiogenesis in ovarian cancer. These results encourage further study of TARS as a regulator of the tumor microenvironment and possible target for diagnosis and/or treatment in ovarian cancer.

CT-guided transthoracic needle aspiration biopsy of subsolid lung lesions.

PURPOSE: To assess the diagnostic performance of computed tomography (CT)-guided transthoracic needle aspiration biopsy (TNAB) in the evaluation of persistent subsolid lung lesions. MATERIALS AND METHODS: A retrospective review of all CT-guided TNABs performed at a single institution from January 2002 to November 2012 was conducted to identify patients with persistent subsolid lung lesions. The diagnostic performance of CT-guided TNAB was assessed through comparison of cytologic diagnoses with core needle biopsy, surgical resection, or imaging and clinical follow-up. The cytologic, histologic, and imaging features of each lesion were characterized, and CT-guided TNAB complications were recorded. RESULTS: In 32 patients, a diagnosis of benign or malignant disease was identified through evaluation of pathologic or follow-up data. There were 18 men and 14 women, with a mean age of 67.1 years ± 9.6 (range, 52-86 y). The mean lesion diameter was 21 mm ± 11 (range, 8-62 mm). A final diagnosis of malignancy was made in 28 cases (87.5%); four benign lesions were also diagnosed. The overall sensitivity of CT-guided TNAB in the evaluation of these lesions was 89.2%, and the specificity and positive predictive value were 100%. Two pneumothoraces (6.3%) were identified. CONCLUSIONS: Among patients with subsolid lung lesions, CT-guided TNAB is safe and shows high sensitivity. The high specificity and positive predictive value of the procedure allow for definitive treatment decisions to be made for most patients.

Testing of integrated human papillomavirus mRNA decreases colposcopy referrals: could a change in human papillomavirus detection methodology lead to more cost-effective patient care?

OBJECTIVES: This study investigates potential colposcopy referral rates, as per the latest American Society for Colposcopy and Cervical Pathology recommendations, following the change in high-risk human papillomavirus (HR-HPV) detection methodology from Hybrid Capture 2 (HC2) to APTIMA at our institution. STUDY DESIGN: Rates of colposcopy referral were compared between two cohorts, each comprising all Pap samples with a diagnosis of atypical squamous cells of undetermined significance (ASCUS) tested for HR-HPV in our laboratory during a 12-month period. Cohorts I and II included Pap samples tested with HC2 (n = 1,856) and APTIMA (n = 1,651), respectively. The rates of quantity not sufficient (QNS) results were determined for all Pap samples during the same time periods. RESULTS: The proportion of HR-HPV-positive Pap samples with an ASCUS diagnosis was significantly lower with APTIMA (42%) than with HC2 (53%; p < 0.0001). APTIMA also resulted in a significantly lower QNS rate among all Pap samples (0.42 vs. 4.3% with HC2; p < 0.0001). CONCLUSION: The change in HR-HPV detection methodology from HC2 to APTIMA has led to a 21% reduction in colposcopy referrals and a 90% decrease in QNS rates at our institution. The new methodology has resulted in more cost-effective patient care and fewer insufficient samples requiring repeat HR-HPV testing.

Müllerian and mesothelial lymph node involvement in patients with borderline ovarian tumors.

OBJECTIVE: To determine the true incidence of Müllerian and mesothelial lymph node involvement in serous and mucinous borderline ovarian tumors (BLOT) with serial sectioning and immunohistochemistry. STUDY DESIGN: Formalinfixed, paraffin-embedded lymph node blocks from patients with serous (N = 21) and mucinous (N = 5) BLOT who underwent lymphadenectomy between 1995 and 2002 were serially sectioned at 5 microm levels with 3 consecutive sections taken at surface, 125 microm and 475 microm. One slide from each level was stained with hematoxylin-eosin (H-E), cytokeratin (AE1-AE3, DAKO) and calretinin (DAKO). Lymph node involvement was defined as epithelioid cells recognized by H-E and confirmed by immunoreaction with keratin (Müllerian) and calretinin (mesothelial) or identified by immunohistochemistry alone. The results obtained by serial sectioning and immunohistochemistry were compared with those obtained by routine histologic examination at the time of the original surgery. RESULTS: A total of 240 lymph nodes (215 from patients with serous and 25 from patients with mucinous BLOT) were examined. Original pathologic examination identified lymph node involvement in 29/215 lymph nodes from 21 patients with serous BLOT. Twelve of the 21 patients with serous BLOT (57%) and none of the 5 patients with mucinous BLOT (0%) demonstrated Müllerian lymph node involvement. Serial sectioning and keratin immunostaining identified Müllerian involvement in 4 (1.6%) and 10 (4.2%) additional nodes not diagnosed in original sections, respectively. However, no additional node-positive patients were identified. Mesothelial involvement was identified in 2 patients (2/26, 7.6%). CONCLUSION: Patients with serous BLOT have a high incidence of Müllerian lymph node involvement. Distinction between Müllerian and mesothelial differentiation may require immunohistochemical study. Compared with routine histologic examination, serial sectioning and immunohistochemical examination yield a higher number of involved lymph nodes.

Smoking increases the risk of high-grade vaginal intraepithelial neoplasia in women with oncogenic human papillomavirus.

OBJECTIVES: In a large retrospective study, the association of smoking with human papillomavirus (HPV) genotype and vaginal intraepithelial neoplasia (VAIN) grade was analyzed. METHODS: A SNOMED search was performed for vaginal biopsy or resection specimens diagnosed as VAIN over an 11-year period. The diagnosis of VAIN grade was confirmed by histological review. HPV genotype was determined by GP5+/6+ PCR and dot blot hybridization with type-specific oligonucleotide probes. Smoking history was obtained by chart review. Statistical analysis was performed using the chi-square test. RESULTS: We identified specimens from 111 patients (age range 15-84); 64% (n=71) were diagnosed with high-grade VAIN (HGVAIN) and 36% (n=40) with low-grade VAIN (LGVAIN). High-risk (HR) HPV genotypes were identified in 83% of specimens (n=92), other types in 17% (n=19). Twenty-one different HPV genotypes were detected in total. Smoking history was available for 81% (n=90). Forty-one percent (n=37) had a positive smoking history. There was no significant difference in infection with HR vs. other types (p=0.92) among smokers when compared to non-smokers. In patients with HR HPV genotypes, smokers were at an increased risk for HGVAIN lesions when compared to patients who had never smoked (83% vs. 59%, p=0.02). CONCLUSIONS: These data indicate an increased risk for HGVAIN in HR HPV positive women who smoke compared to HR HPV positive non-smokers.

Clinical and molecular differences between clear cell and papillary serous ovarian carcinoma.

PURPOSE: The aim of the current study is to compare clear cell ovarian carcinoma (CCOC) and papillary serous ovarian carcinoma (PSOC) with respect to their clinical features and expression of different regulators of cell cycle, apoptosis, and chemoresistance. EXPERIMENTAL DESIGN: Women with stage III CCOC (n = 9) and those with stage III, poorly differentiated PSOC (n = 21) seen between 1996 and 2000 and treated with cytoreductive surgery followed by paclitaxel and platinum chemotherapy were compared in their demographic features, tumor marker profile, surgical substage, results of cytoreductive surgery, thromboembolic complications, response to chemotherapy, and tumor recurrence. Tumor samples were compared in their expression of p53, Bcl(2), Bcl(x), Bax, p21, p-glycoprotein (PGP), multi-drug resistance-associated protein (MRP), lung resistance protein (LRP), and glutathione S-transferase (GST) using immunohistochemistry. RESULTS: Women with CCOC had significantly lower mean preoperative CA-125 values, lower surgical substage, less expression of p53, and more expression of p21 than women with PSOC (P = 0.037, 0.012, 0.008, and 0.009, respectively). Women with CCOC had less ascites, smaller amount of residual tumor, higher incidence of thromboembolism, chemoresistance, more expression of Bcl(2), and less expression of PGP than women with PSOC (P = 0.067, 0.078, 0.108, 0.114, 0.091, and 0.118, respectively). CONCLUSIONS: Women with CCOC exhibit certain clinical and molecular differences compared to stage- and grade-matched women with PSOC. Women with CCOC have a smaller tumor volume and manifest different expressions of p53, p21, and Bcl(2) than women with PSOC. Although further studies with larger number of patients are needed, our findings indicate that chemoresistance in CCOC is probably not p53-dependent.

Laparoscopic surgery does not increase the positive peritoneal cytology among women with endometrial carcinoma.

OBJECTIVE: The purpose of our study was to find if uterine manipulation at the time of laparoscopic hysterectomy among women with endometrial carcinoma increases the incidence of malignant cells in the peritoneal washings. MATERIAL AND METHODS: We conducted a prospective study including women with clinical stage I endometrioid endometrial carcinoma undergoing laparoscopic surgery between 07/01/2000 and 07/01/2004. Surgery on all patients was conducted by the same surgeon using the same technique and instruments. Two sets of peritoneal washings were obtained, one before and one after the insertion of the Pelosi uterine manipulator. The two sets of washings were blindly reviewed by the same cytopathologist for the presence of malignant cells. Correlation was made between the two sets of washings. RESULTS: Forty-two consecutive women (age 46-90, median: 58) were enrolled in the study. The procedure was converted to laparotomy in 3 (7.6%) patients after obtaining the two sets of washings. The preoperative tumor grades were: G1: 22 (52.4%), G2: 12 (28.6%), and G3: 8 (19.0). The incidence of positive peritoneal washings was 14.3%. All patients underwent laparoscopically assisted vaginal hysterectomy with bilateral salpingo-oophorectomy, 30 patients had bilateral pelvic lymphadenectomy, and 5 patients had bilateral pelvic and para-aortic lymphadenectomy. There was perfect agreement between the two sets of washings in all patients (100%, P < .001). No patients had positive washings after the insertion of the uterine manipulator if the washings were negative before the insertion. The surgical stages were: IA: 14 (33.3%), IB: 12 (28.6%), IC: 7 (16.7%), IIA: 1 (2.4%), IIB: 1 (2.4%), IIIA: 4 (9.5%), IIIB: 1 (2.4%), IIIC: 1 (2.4%), and IV: 1 (2.4%). Twenty-nine patients received no postoperative treatment, 2 received chemotherapy, 3 received Megace, and 9 received radiation therapy. Patients were followed-up for 7-56 months (median: 28). Two patients had tumor recurrence, and one patient died secondary to her disease. Two other patients died secondary to other causes. CONCLUSIONS: We conclude that uterine manipulation at the time of laparoscopic hysterectomy does not increase the incidence of positive peritoneal cytology among women with endometrial carcinoma.

Surgical stage, final grade, and survival of women with endometrial carcinoma whose preoperative endometrial biopsy shows well-differentiated tumors.

OBJECTIVE: The purpose of our study was to assess the surgical stage, final grade, and survival of women with endometrial carcinoma whose preoperative endometrial biopsy showed well-differentiated (FIGO grade 1) carcinoma. MATERIALS AND METHODS: A retrospective study was conducted including all women treated at the University of Vermont between 1992 and 2004 whose preoperative endometrial biopsy was reviewed by the staff at the Pathology Department and diagnosed as FIGO grade 1 adenocarcinoma and who received peritoneal washings, total abdominal (or laparoscopic) hysterectomy, bilateral salpingo-oophorectomy, and pelvic +/- para-aortic lymphadenectomy as part of their surgery. RESULTS: One hundred eighty-two patients (age: 32-91, median: 60) were enrolled. All patients had total hysterectomy, bilateral salpingo-oophorectomy, peritoneal washings, and bilateral pelvic lymphadenectomy. Fifteen (8.2%) patients had para-aortic lymphadenectomy. There were no operative mortalities. Fourteen patients (7.7%) had major operative or postoperative complications. There was disagreement between the pre- and postoperative grade in 30% of the study group. The surgical stages were: IA: 55 (30.2%), IB: 61 (33.5%), IC: 26 (14.3%), IIA: 9 (4.9%), IIB: 8 (4.4%), IIIA: 10 (5.5%), IIIB: 2 (1.1%), IIIC: 8 (4.4%), and IV: 3 (1.6%). Postoperatively, 131 (72%) patients received no additional treatment, 47 (25.8%) received radiation therapy, 3 (1.6%) received chemotherapy, and 1 (0.5%) received Megace. During a median follow-up period of 6 years, 8 (4.4%) patients had recurrence and 6 (3.2%) died from their disease. The 5-year disease-free and overall survival was 95.2% and 96.4%, respectively. CONCLUSIONS: Approximately 30% of women with endometrial carcinoma whose preoperative endometrial biopsy shows grade 1 tumors have grade 2 or 3 in the hysterectomy specimen and 12.6% have advanced surgical stage (stage III and IV) disease. Women with preoperative endometrial biopsy showing grade 1 tumors who undergo surgical staging have excellent survival and acceptable operative morbidity.

Gastrointestinal stromal tumor of the stomach with rhabdoid phenotype: immunohistochemical, ultrastructural, and immunoelectron microscopic evaluation.

A variety of neoplasms with rhabdoid differentiation have been reported in many sites. The authors describe a case of gastrointestinal stromal tumor (GIST) of the stomach that exhibited prominent rhabdoid features. Immunohistochemically, the tumor cells displayed positive staining for vimentin, c-kit, CD34, and alpha smooth muscle actin. Ultrastructural examination of the rhabdoid tumor cells revealed paranuclear whorls of intermediate filaments, which were immunoreactive for vimentin by both light microscopic immunohistochemical and protein A gold immunoelectron microscopic techniques. On H&E light microscopic examination alone, such a tumor could be mistaken for a variety of epithelial, mesenchymal, or other neoplasms that may show rhabdoid features. One report of GIST with a rhabdoid histologic phenotype has been described. This is the second known report of such a case with immunophenotypic and ultrastructural evaluation, and the first case with immunoelectron microscopic examination.

Factors associated with cytoreducibility among women with ovarian carcinoma.

OBJECTIVES: The aim of the current study is to investigate the clinical and molecular factors associated with cytoreduction among women with advanced stage epithelial ovarian carcinoma EOC. METHODS: Seventy-two women with FIGO stage III and IV EOC or primary peritoneal carcinoma (PPC) underwent similar attempt at surgical cytoreduction, mostly by the same surgeon. The histologic material of these patients was reviewed and the histologic subtype and grade were assigned. Immunohistochemical tests were performed for expression of molecular regulators of apoptosis (p53, p21, Bcl(2), Bcl(x), Bax) and chemoresistance (PGP, MRP, LRP, GST). The following factors were assessed for their association with complete (no residual tumor) and optimal (residual tumor < 1 cm) cytoreduction: type of carcinoma (EOC versus PPC), stage, CA-125 values, ascites, histology, tumor grade, and p53, p21, Bcl(2), Bcl(x), Bax, PGP, MRP, LRP, GST expression using the odds ratio and associated 95% confidence intervals. Significant univariate odds ratios were assessed jointly in a multivariate logistic regression model. Receiver operating characteristic curve analysis was performed to determine the CA-125 level with the maximal cytoreduction prognostic power. RESULTS: Twenty-three (31.9%) women had no residual tumor, 35 (48.6%) had 1 cm. Factors with significant univariate associations with complete cytoreduction included stage, CA-125 level, ascites, histology, and p53. p53 expression was the only factor which remained significant in the multivariate analysis (odds ratio 7.2, 95% CI 1.5, 34.9). A preoperative CA-125 value of

Recurrent perivascular epithelioid cell tumor of the uterus (PEComa): an immunohistochemical study and review of the literature.

BACKGROUND: Neoplasms of the perivascular epithelioid cell, first described in 1992, comprise a family of tumors known as "PEComas." To the best of our knowledge, this is the third case of uterine PEComa reported in the literature to behave in a malignant fashion. The purpose of this report is to provide information that may be used to predict the future behavior of this tumor. CASE: The patient was a 79-year-old woman with a large uterine mass which recurred 2 years following resection. The patient died within months after resection of the recurrent tumor. Retrospective immunohistochemical staining with newly commercially available antibodies including MART-1 was done on both the original and the recurrent tumor, confirming the diagnosis of uterine PEComa. CONCLUSION: Uterine PEComas should be regarded as tumors with uncertain malignant potential.

Positive predictive value of liquid-based and conventional cervical Papanicolaou smears reported as malignant.

OBJECTIVES: The predictive value of cervical Papanicolaou (Pap) smears reported as "positive for malignancy," especially those obtained by the liquid-based method, has not been adequately assessed. The objectives of this study are to determine the positive predictive value of Papanicolaou smears with features of malignancy, to compare the accuracy of Papanicolaou smears obtained by the liquid-based method to those obtained by the conventional technique in this setting, and to study the factors influencing a false-positive cytologic diagnosis of malignancy. MATERIALS AND METHODS: Pap smears significant for malignant cytology were identified at Fletcher Allen Health Care Hospital in Burlington, VT, from May 1, 1995, to April 30, 2001. A retrospective review of the hospital records and pathology reports was performed documenting patient characteristics, the collection technique, and the final histology. An independent review of the cytology and histology was performed. The positive predictive value and false-positive rate of malignant cytology were calculated for the liquid-based and conventional Pap smear techniques. RESULTS: A total of 472,743 Pap smears were performed during the period specified. One hundred four Pap smears were reported as positive for malignancy, yielding a prevalence rate of 0.02%. A total of 68 patients had paired cytology and histology specimens. Malignant cytology was identified in 36 smears obtained by the liquid-based technique and 32 smears obtained by the conventional technique. A true-positive result, meaning malignant cytology confirmed by the presence of invasive carcinoma on histology, was obtained in 61 of 68 (89.7%) patients. A false-positive result, meaning malignant cytology not confirmed by histology, was obtained in 7 of the 68 (10.3%) patients. The false-positive rate of malignant cytology was 8.4% for the liquid-based technique and 12.5% for the conventional technique. All 7 false-positive smears were diagnosed with high-grade dysplasia by histology. Three of the 7 patients with high-grade dysplasia had previous treatment for dysplasia, one of whom was also pregnant at the time of the smear. CONCLUSIONS: Malignant cervical Papanicolaou smear cytology has a high positive predictive value in the setting of gynecologic and nongynecologic malignancies. Previous treatment for cervical dysplasia or pregnancy may influence the false-positive rate of malignant cytology.