The effect of surgical margin on cancer-specific survival in patients treated with nephron-sparing surgery.

BACKGROUND: Nephron-sparing surgery (NSS) is currently the recommended treatment modality for selected renal tumors. The prognostic significance of positive surgical margin (PSM) and surgical margin width (SMW) after NSS is controversial. AIM: To evaluate the effect of PSM and SMW on cancer-specific survival (CSS) in patients who underwent NSS. MATERIALS AND METHODS: The pathological samples of 142 patients who underwent NSS were reviewed. Patients were divided into two groups with PSM and negative surgical margin (NSM), and after that those with PSM were divided into two groups according to SMW as those with 0.1-2 mm and those >2 mm. CSS was calculated using Kaplan-Meier method. Cox regression analysis was used to adjust the clinicopathologic variables. A P value < 0.05 was considered statistically significant. RESULTS: Local recurrence rate and distant metastasis rate were higher in patients with PSMs than those with NSMs (P = 0.018 and P = 0.039, respectively). However, there was no significant difference between the two groups in terms of CSS. In the group with SMW 0.1-2 mm, the tumor diameter was longer (P = 0.018), enucleation number was higher (P = 0.026), and local recurrence was higher (P = 0.034) than the group with SMW > 2 mm. There was no significant difference between the two groups in terms of CSS. CONCLUSION: In patients who underwent NSS, PSMs and SMWs have a negative effect on local recurrence but have no significant effect on CSS.

Correlation of the in situ detection of polymerase chain reaction-amplified metalloproteinase complementary DNAs and their inhibitors with prognosis in cervical carcinoma.

The purpose of this study was to correlate the presence of matrix metalloproteinase (MMP)-9 and MMP-2 and tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 mRNAs, detected in serial sections using the reverse transcriptase in situ PCR technique, with prognosis in 23 cases of cervical carcinoma. PCR-amplified MMP and TIMP cDNA were restricted to the invasive cancers cells and the surrounding stromal cells. The ratios of cancer and stromal cells expressing MMP-9 and MMP-2 to those expressing TIMP-1 and TIMP-2 were approximately 1 in those cancers with a good prognosis. This MMP:TIMP ratio in the cancer and stromal cells with a poor prognosis was significantly increased to 5.4 and 3.4 (P < 0.0001), respectively, reflecting a marked reduction in the TIMP detection rate in cancers with a poor prognosis. In cervical cancer cell lines SiHa and HeLa, the MMP:TIMP ratio was also close to 1 and, interestingly, these cell lines are invasive but rarely metastatic in nude mice. These data suggest that the balance of MMP-9 and MMP-2 to TIMP-1 and TIMP-2 expression is an essential factor in the aggressiveness of cervical cancer.

Late fatal adenovirus pneumonitis in a lung transplant recipient.

Adenovirus (ADV) is increasingly recognized as a cause of morbidity and mortality in transplant recipients, but ADV pneumonitis has rarely been reported after lung transplantation. The few reported instances of ADV pneumonitis occurred mostly in children immediately after lung transplantation suggesting "primary" infection. We report a fatal case of ADV pneumonitis occurring in an adult, 4 years after unilateral lung transplantation, in whom the premortem diagnosis was not determined. Autopsy revealed severe necrotizing bronchitis, bronchiolitis, and interstitial pneumonitis. Characteristic smudgy intranuclear inclusions, immunohistochemistry for viral protein, in situ hybridization for viral genome, and postmortem lung cultures established ADV as the etiologic agent. ADV can cause fatal, occult respiratory infection in adult lung transplant recipients, remote from transplant surgery.

Malignant granular cell tumor: a case report and review of the recent literature.

We report a case of an extremely rare neoplasm, malignant granular cell tumor (MGCT). The tumor occurred in the infratemporal fossa of a 30-year-old man, extended to the left orbital base, into the foramen ovale, and invaded the mandible. A granular cell tumor (GCT) was diagnosed by fine-needle aspiration and core needle biopsy of the mass. The patient underwent a radical subtotal debulking procedure followed by radiotherapy. He is alive with recurrent disease 12 months after presentation. Cytologically, the aspirated material was abundantly cellular showing large polygonal cells with ample granular eosinophilic cytoplasm, eccentric nuclei, and often prominent nucleoli. Histologically, the tumor consisted of solid sheets of similar cells that stained strongly with S-100 protein, neuron-specific enolase (NSE), and vimentin. There was moderate nuclear pleomorphism and broad zones of necrosis. Four mitotic figures per 100 high-power field (HPF) were counted. By electron microscopy, the cytoplasm of the tumor cells was filled with lysosomes. Although, some observers advocate that the diagnosis of a MGCT should be reserved for cases in which lymph node and/or distant organ metastasis is evident, we believe malignancy ought to be considered in any GCT with aggressive clinical course defined by persistent local recurrence and destruction of neighboring structures. Nuclear pleomorphism, necrosis, and presence of any mitotic activity should indicate malignancy.

Human polyoma virus in renal allograft biopsies: morphological findings and correlation with urine cytology.

Human polyoma virus (PV) interstitial nephritis occurs in immunosuppressed patients after reactivation of latent virus in renal epithelium. Currently, there is neither general consensus about the incidence of clinically significant PV infection in renal transplants nor conclusive evidence determining its significance in the long-term graft outcome. We evaluated 601 renal transplant biopsy specimens (from 365 patients) by routine light microscopy and immunoperoxidase stains with antibody against SV40 (which cross reacts with PV). We also examined urine samples from 200 patients (100 obtained concurrently with a renal biopsy in patients presenting with acute graft dysfunction and 100 from patients with stable graft function). Electron microscopic evaluation was performed in 50 renal biopsy specimens and in 23% of all urine samples. PV was identified in 1.8% biopsy specimens (1.9% of patients). PV interstitial nephritis showed the typical viral cytopathic changes in tubular epithelial cells associated with marked tubular damage and a disproportionately mild degree of tubulitis. There was no difference in the incidence of PV in the urine of patients with acutely deteriorating versus stable renal function (18% and 19%, respectively); however, urines with large numbers of infected cells (> 10/cytospin) and inflammatory changes in the sediments corresponded invariably to patients with acute allograft dysfunction (8 of 8), and in most cases to biopsy specimens showing PV interstitial nephritis (7 of 8). Based on these findings, urine samples seem to be the most sensitive and cost-effective screening method for PV infection; only urine samples with inflamed sediments and abundant infected cells correlate with clinically significant disease. In these cases, examination of a renal biopsy is indicated. Immunohistochemical stains are useful to confirm the presence of PV but do not increase the sensitivity of diagnosis of PV if this is not already suspected on routine light microscopy. In our material, immunostains were helpful ruling out the presence of PV in a small number of biopsy specimens (2%) that showed markedly reactive tubular cells resembling PV infection. Most patients with PV interstitial nephritis responded to decreased immunosuppression; however, the decay in graft function (based on creatinine slopes) was significantly more rapid in these patients than in matched controls. Evidence of PV infection should be systematically sought in renal biopsy specimens and urine samples from renal allograft recipients.

Additional mimics of mucinous mammary carcinoma: fibroepithelial lesions.

To determine the origin and nature of mucinlike material in fine-needle aspiration (FNA) smears of the breast in noncancerous breast lesions, we studied breast FNA smears from four patients. All smears contained epithelial cells floating in a mucinlike background, which raised suspicion for mucinous (colloid) carcinoma. Mucicarmine stain was performed on one smear from each case. Subsequent tissue biopsy specimens were studied using mucicarmine, periodic acid-Schiff with and without diastase, and alcian blue stains at pH 2.7 and 0.9 on selected tissue sections. Correlation of the cytologic and histologic findings of each lesion was performed. The mucinlike background in all four FNA smears stained strongly with mucicarmine. Corresponding biopsy specimens revealed pseudoangiomatous hyperplasia in the first case, fibroadenoma and atypical ductal hyperplasia in the second, benign phyllodes tumor in the third, and fibroadenoma in the fourth. Each lesion in cases 1 to 3 was associated closely with fibrocystic changes. In case 4, cystic changes were located within the fibroadenoma. On tissue sections of all four cases, the cyst contents and 10% to 50% of normal lobule and duct contents stained with mucicarmine, indicating that the cyst contents were the most probable source of mucin in the FNA smears. The presence of pools of mucicarmine-positive material in FNA smears of the breast is not an exclusive feature of mucinous carcinoma; mucicarmine-positive mucin can arise from benign cystic changes as well as from normal lobules and ducts.

Endometriosis in abdominal scars: a report of three cases diagnosed by fine-needle aspiration biopsy.

Endometrioma in an operative scar is rare. The majority of patients have no prior history of endometriosis, and symptoms may mimic postoperative hernias. Fine-needle aspiration biopsy (FNAB) can be a valuable diagnostic aid in the evaluation of these subcutaneous abdominal masses. We present the cytologic findings in three cases of abdominal wall endometriomas diagnosed by FNAB. The patients ranged from 31 to 51 years of age. None had a history of endometriosis, but all had prior abdominal operations (two abdominal hysterectomies for fibroids and one cesarean section). They presented 6 months to 7 years later with painful subcutaneous abdominal nodules in their scars ranging from 2 to 6 cm. FNAB was performed by a cytopathologist. The smears were cellular and comprised two distinct cell populations. An epithelial component consisted of flat sheets of polygonal cells with round to oval nuclei and scant cytoplasm. The second component consisted of clusters of fusiform stromal cells. Numerous hemosiderin-laden macrophages were noted in the background. Cytokeratin highlighted the epithelial clusters, and vimentin stained the stromal cells. Electron microscopy showed two epithelial cell types: one with cilia and abundant rough endoplasmic reticulum and the other with numerous microvilli and scattered mitochondria indicative of endometrial differentiation. FNAB provided a rapid and accurate preoperative diagnosis in each case.

Fibroadenomas with atypia: causes of under- and overdiagnosis by aspiration biopsy.

Fibroadenoma (FA) is a common benign breast lesion frequently sampled by fine-needle aspiration biopsy (FNAB). Although the cytologic diagnosis is straightforward in most cases, cellular discohesion and atypia in FAs may lead to falsely atypical or positive FNAB diagnoses. Conversely, some adenocarcinomas mimic a fibroadenomatous pattern on FNAB, resulting in a false-negative diagnosis. We reviewed the cytologic and histologic findings in 25 cases with a preoperative FNAB diagnosis of FA, wherein excision was recommended based on atypia. Our aim was to analyze the spectrum of changes causing under- or overdiagnosis in such cases. The smears were assessed for cellularity, cellular discohesion, presence of dissociated intact cells and nucleoli, nuclear pleomorphism, oval bare nuclei, and stromal fragments. The histologic findings were correlated with FNAB features. At excision, 88% of FAs classified as atypical on FNAB were benign (FA with ductal hyperplasia and lactational change, myxoid FA, and other fibroepithelial lesions). Differentiating myxoid FA from colloid carcinoma was difficult due to the abundance of extracellular mucin in which the dissociated epithelial cells were floating. Two (8%) cases were carcinomas on excision; the reasons for underdiagnosis in one case reflected sampling, and in the other, interpretative error. There was one (4%) benign phyllodes tumor which lacked stromal fragments and single stromal cells on FNAB smears. The lesion was called atypical, based on the epithelial discohesion on the smears. We conclude that the majority of FAs with atypia on FNAB are benign lesions. Considering the grave consequences of a false-positive cytologic diagnosis, we recommend a conservative approach in interpreting FNAB smears which overall display a fibroadenomatous pattern.

Rhodococcus equi and cytomegalovirus pneumonia in a renal transplant patient: diagnosis by fine-needle aspiration biopsy.

Rhodococcus equi is a common cause of pneumonia in animals. Human infection is rare. Increasing number of cases are being reported in immunosuppressed individuals mostly associated with HIV infection, but also in solid organ transplant recipients and leukemia/lymphoma patients. We report on an adult male who developed pneumonia and gastroenteritis 4 mo after receiving a renal transplant. CT scan of the lungs showed a dominant 2.5-cm upper lobe lung mass and smaller bilateral nodules. He underwent a diagnostic bronchoscopy with fine-needle aspiration biopsy of the largest lung nodule. Smears showed histiocytic granulomatous inflammation, foamy macrophages, and acute inflammatory exudate. Scattered foamy macrophages displayed intracellular coccobacilli identifiable on Diff-Quik stain. A few cells with changes suggestive of viral inclusions were identified. Cytomegalovirus (CMV) immunostain was positive in the cell block sections. Lung cultures grew R. equi. To the best of our knowledge, this is the first report of coinfection with R. equi and CMV.

Aspiration cytology of the collagenized variant of mammary myofibroblastoma: a case report with review of the literature.

Myofibroblastoma of the breast is a rare benign stromal neoplasm, which occurs primarily in men. Classical myofibroblastoma is a circumscribed, nonencapsulated tumor comprised of bipolar fusiform cells arranged randomly, or in fascicles alternating with broad collagenous bands. Additional histologic variants (the cellular, collagenized, infiltrative, and epitheloid types) have been described. Several case reports describe the cytopathologic features of the classical and cellular variants. We report on a 70-yr-old woman, who presented with a circumscribed mass in her left breast. Aspiration biopsy showed paucicellular smears with singly distributed atypical spindle-shaped cells and rare fragments of collagenized stroma, raising suspicion of a phyllodes tumor. Histologic examination revealed spindle-shaped cells distributed in a diffusely collagenized stroma. Some nuclear atypia was present. To the best of our knowledge, this is the first case reporting the cytologic features of the collagenized variant of myofibroblastoma. Although we believe a specific diagnosis of myofibroblastoma can be rendered in a male based on the typical cytologic and clinical findings in the classical type, the variant forms are difficult to classify accurately and require excision for a definitive diagnosis.

Comparison of antibodies to HBME-1 and calretinin for the detection of mesothelial cells in effusion cytology.

The distinction of mesothelial cells in cytologic samples is often a diagnostic challenge. This is particularly true in potentially malignant effusions in which reactive mesothelial cells may simulate adenocarcinoma (ACA) cells, and in the differentiation of ACA vs. mesothelioma. We sought to determine the superior antibody for the positive identification of mesothelial cells in these circumstances. Cell block sections of 25 reactive and 8 malignant mesothelioma effusions were immunostained with an avidin-biotin procedure, using antibodies to HBME-1 and calretinin. No pretreatment of samples was necessary for the HBME-1-stained slides; microwave antigen retrieval was performed on all slides stained for calretinin. A negative control was performed on each sample. The staining intensity of tumor cells was scored on a scale of 0-3+, with the proportion of immunoreactive cells categorized as <25%, 25-50%, 50-75%, and >75%. The predominant staining pattern for HBME-1 was surface, with rare samples also exhibiting cytoplasmic staining as well. The calretinin-staining pattern was cytoplasmic, with peripheral condensation/prominence and accompanying nuclear staining. All samples were immunoreactive with both antibodies. Fifty-five percent (18/33) of samples showed significantly stronger immunoreactivity with calretinin than with HBME-1; 45% (15/33) of samples showed equivalent staining with the two markers. None of the samples in this study showed stronger immunoreactivity with HBME-1 than with calretinin. Sixty-one percent (20/33) of samples stained with HBME-1 at a moderate (2+) intensity. Fifty-five percent (18/33) of samples stained with calretinin at a strong (3+) intensity. While only 12% of samples showed >75% immunoreactivity for HBME-1, 58% of samples showed >75% of cells immunoreactive for calretinin. Calretinin is the preferred marker in identifying mesothelial cells in cytologic samples, showing the highest sensitivity for mesothelial cells, as evidenced by a more intense staining reaction in a higher percentage of cells than with HBME-1. Published 2001 Wiley-Liss, Inc.

Cytologic features of tubular adenocarcinoma of the breast by aspiration biopsy.

Tubular adenocarcinoma is an invasive mammary adenocarcinoma associated with an excellent prognosis and a low incidence of axillary metastases. However, identification of tubular adenocarcinoma by fine-needle aspiration (FNA) biopsy has proven difficult. One hundred five patients with documented "pure" tubular adenocarcinoma were diagnosed at Tisch Hospital from August of 1992 to December of 1998. Twenty-one of these patients had an FNA before excision. We reviewed the smears of these cases and compared them with cases of fibroadenoma and fibrocystic change to identify criteria for diagnosis. Moderately to highly cellular smears with angular cellular clusters with sharp borders and oval cells outlining these clusters, dispersed single cells with minimal atypia, and the absence or paucity of dispersed bare oval nuclei in the background were features that suggest a diagnosis of tubular adenocarcinoma in our study. Attention to these features in combination with appropriate mammographic findings should preclude a false-negative diagnosis in the majority of cases of tubular adenocarcinoma diagnosed by aspiration biopsy. We point to the presence of the peripheral perpendicular cells in the characteristic tubular arrays as an important clue to the diagnosis of tubular adenocarcinoma.

Extrapulmonary tuberculosis as a mimicker of neoplasia.

Despite the efforts for control and eradication of tuberculosis, new cases of the disease are diagnosed daily. The diagnosis of tuberculosis is easily made when the classical features of pulmonary necrotizing granulomatous inflammation are seen. However, extrapulmonary lesions may clinically and radiographically mimic a neoplastic process, and this may lead to misdiagnosis and delay in treatment. We studied 6 patients by aspiration biopsy, all recent immigrants and immunocompetent, who presented with weight loss and fatigue. Of these, 5 patients had a mass. One patient presented with a lytic lesion of bone. In all cases the clinical diagnosis was neoplasia. In all aspirates, the smears showed necrotic debris with neutrophils. No neoplastic cells or granulomas were seen. All cases were signed out descriptively with no specific diagnosis. A search for acid-fast organisms leading to the correct diagnosis of tuberculosis was prompted by clinical investigations that revealed pulmonary lesions, or by repeat aspiration biopsy, which showed granulomatous inflammation. Tuberculosis when present in atypical forms is still a challenging diagnosis. The finding of necrotic debris in a needle biopsy without the clinical signs of an abscess should prompt a search for acid-fast bacilli, since the correct diagnosis will eliminate a needless surgical procedure and will lead to timely and appropriate therapy.

Biliary stent replacement cytology.

Using fluoroscopic guidance, polyethylene biliary stents are replaced endoscopically or percutaneously when bile duct stenosis recurs. To improve the sensitivity of conventional biliary cytology, we examined cells recovered from removed stents. Biliary stents removed endoscopically from each of 11 patients were rinsed with saline; next, the rinse was centrifuged and the sediment smeared and Papanicolaou stained. Three patients with choledocholithiasis had biliary stent replacement cytology (BSRC) to exclude a neoplastic etiology. Eight patients with clinicoradiologic evidence of hepatobiliary or pancreatic carcinoma had BSRCs performed for pathologic documentation of carcinoma. BSRC from six of eight patients with clinicoradiologically malignant biliary strictures contained malignant cells, predominantly in loose clusters, but also singly (sensitivity 75%, specificity 100%; positive predictive value 75%, negative predicative value 60%). Reparative epithelial atypia was also present in all cases. BSRC from two patients with clinicoradiological evidence of carcinoma of the biliary region and from three with choledocholithiasis contained only bile pigment, leukocytes, and benign epithelial cells. The sampling of cells which have accumulated on, or in biliary stents, improves the sensitivity of biliary cytology. This is most applicable when 1) a patient is inoperable, 2) tissue biopsy is neither feasible nor diagnostic, 3) prior brush, suction, percutaneous, or endoscopic needle aspiration cytology is inconclusive, and 4) permanent metal stent is needed.

E-cadherin, N-cadherin, and calretinin in pleural effusions: the good, the bad, the worthless.

The distinction between reactive mesothelial cells (RMC), malignant mesothelioma (MM), and metastatic adenocarcinoma (ACA) in pleural effusions may be impossible based on morphology alone. E-cadherin, N-cadherin, and calretinin are newly described immunocytochemical markers which can potentially be utilized for facilitating this distinction. E-cadherin and N-cadherin are calcium-dependent intercellular adhesion molecules expressed in epithelial cells and mesenchymal/mesothelial cells, respectively. The differential expression of E-cadherins in epithelial cells and N-cadherins in mesothelial cells has been utilized to differentiate reactive mesothelial cells, MMs and ACAs. Calretinin is a calcium-binding protein within the family of EF-hand proteins. It is abundantly expressed in peripheral and central nervous tissues, and has been shown to consistently immunoreact with mesothelial cells. We studied cell block sections from 77 pleural effusions (22 RMC, 26 MM, and 29 ACA) to investigate the potential immunocytochemical use of anti-E-cadherin, anti-N-cadherin, and anti-calretinin antibodies for differentiating between RMC, MM, and ACA in pleural effusions. A modified avidin-biotin peroxidase complex (ABC) method was used. E-cadherin immunostaining was observed in 14% of RMC, 46% of MMs, and 97% of ACAs. A distinct membrane staining pattern was seen in ACAs. The pattern of staining was cytoplasmic in all reactive RMC and varied from membrane to cytoplasmic in MMs. Anti-N-cadherin immunoreacted with 77% of RMC, 35% of MMs, and 48% of ACAs. Twenty-seven percent of RMC, 58% of MMs, and 31% of ACAs immunoreacted with anti-calretinin. Based on these results, we conclude that anti-E-cadherin is a potentially useful marker in the distinction of ACA cells from RMC. However, it is not as useful for the distinction of ACA and MM. Anti-N-cadherin and anti-calretinin did not reliably distinguish between reactive mesothelial, MM, and ACA cells in pleural effusions.

Immunophenotypic analysis of non-Hodgkin's lymphomas in cytologic specimens: a correlative study of immunocytochemical and flow cytometric techniques.

Most Non-Hodgkin's lymphomas(NHL) can be accurately diagnosed and classified based on morphologic and immunophenotypic findings on cytologic specimens. Immunophenotyping can be accomplished via immunocytochemistry (IC) or flow cytometry (FC). We reviewed our experience with 98 cytology specimens (70 fine-needle aspirates [FNA] and 28 effusions) that were submitted for immunophenotyping utilizing both IC and FC between January 1992 and December 1997 for the diagnosis of NHL. Eighty-five percent of the cases were immunophenotyped by both techniques. Among these there were only two discrepancies between IC and FC, yielding a 98% correlation rate. Of the 98 cases, 11% could not be immunophenotyped by FC and 4% could not be immunophenotyped by IC. The advantage of IC is the preservation of cytomorphology, which results in the requirement for a lower number of neoplastic cells and a limited, targeted panel of antibodies. This is especially useful in predominantly necrotic lymphomas in which only a few well-preserved neoplastic cells may be present, rendering the specimen inadequate for immunophenotyping by FC. The advantages of FC are in the detection of a small population of monoclonal cells in a background of reactive cells (particularly useful in effusion samples in which the predominant cell population is often reactive T lymphocytes), increased diagnostic precision through evaluation of objective parameters, and the use of multiple markers with dual labelling. We conclude that IC and FC are both excellent methods for immunophenotyping of cytology specimens and can be used interchangeably depending on the institutional expertise and availability.

Absence of SV-40 large T antigen (Tag) in malignant mesothelioma effusions: an immunocytochemical study.

Simian Virus 40 (SV 40) was recently implicated in the pathogenesis of malignant mesothelioma. The oncogenic capacity of SV-40 is a function of a nuclear protein, the large T antigen (Tag). SV-40 Tag DNA sequences are detected by the polymerase chain reaction in 40-80% of malignant mesothelial proliferations. However, the role of immunohistochemistry (IHC) in demonstrating the nuclear localization of Tag is controversial. We sought to determine the clinical utility of SV-40 Tag IHC in pleural effusion cytology as an ancillary tool in the cytologic diagnosis of malignant mesothelioma (MM). Formalin-fixed, paraffin-embedded cell block sections from 100 pleural effusions (32 MMs, 25 benign reactive, 43 metastatic adenocarcinomas) were immunostained for the SV-40 anti-Tag, using two primary monoclonal SV-40 Tag antibodies: clone Pab 416 and clone Pab 101. Despite strong and consistent immunoreactivity in positive controls, no nuclear immunostaining was observed in any case. We believe the small sample size in cytology cell block sections, the low viral copy number in infected cells, and the effect of formalin fixation may have resulted in absence of immunoreactivity. The role of SV-40 Tag IHC in diagnostic cytopathology remains unclear unless further studies reliably show its detection.

Detection of loss of heterozygosity at chromosome 3p25-26 in primary and metastatic ovarian clear-cell carcinoma: utilization of microdissection and polymerase chain reaction in archival tissues.

Loss of heterozygosity (LOH) at the 3p region is found in up to 50% of epithelial ovarian neoplasms. The von Hippel-Lindau (VHL) gene at the 3p25 locus is one of the tumor-suppressor genes located at 3p. The role, if any, of the VHL gene locus is not clear in ovarian carcinogenesis. We analyzed primary and metastatic ovarian clear-cell carcinomas (OCCC) for LOH at 3p25 to determine its frequency and its diagnostic utility as an adjunctive tool in the differential diagnosis of metastatic clear-cell carcinomas. Microdissection followed by single-step DNA extraction and polymerase chain reaction (PCR) amplification, using two polymorphic markers flanking the VHL gene locus, was done on archival histology and cytology samples from 9 patients with metastatic OCCC. Of the informative cases, 43% of the metastatic and 50% of the primary OCCC showed LOH. LOH at the VHL gene locus is not uncommon in clear-cell ovarian carcinoma. LOH at 3p25 in cytologic specimens may be a valuable adjunct in the diagnosis of OCCC metastasis in cytologically equivocal cases. OCCC should enter the differential in clear-cell carcinomas of unknown primary that show LOH at 3p25. Published 2001 Wiley-Liss, Inc.

CA-125 and carcinoembryonic antigen assay vs. cytodiagnostic experience in the classification of benign ovarian cysts.

OBJECTIVE: To compare the relative strengths of two factors involved in making an accurate differentiation between functional and epithelial ovarian cysts, along with their combination: (1) the cytologist's level of experience in interpreting ovarian cytology, (2) the use of the tumor markers carcinoembryonic antigen (CEA) and CA-125 in cyst fluid, and (3) a combination of (1) and (2). STUDY DESIGN: Papanicolaou-stained sediments from fluid aspirated from 31 resected ovarian cysts (6 functional and 25 epithelial) were blindly and independently evaluated by five pathologists with varying experience in ovarian cytology. Cyst fluid supernatant was used for CEA, enzyme-linked immunosorbent assay, and CA-125 radioimmunoassay; CEA levels > 5 ng/mL or CA-125 > 5,000 U/mL were considered elevated. Cysts were categorized cytologically and histologically as functional or epithelial and by tumor markers as "neither elevated" or "either or both elevated" (EBE). RESULTS: The agreement of histologic diagnosis with each pathologist's cytologic diagnosis ranged from 53% to 84% (53%, 71%, 83%, 82%, 84%), corresponding to increasing level of experience. The percentage of agreement with EBE was 77%, whereas combined experienced pathologist's diagnosis and EBE was 87%. Kappa equaled .45 for experienced cytopathologist's diagnosis or EBE alone. Kappa equaled .53 when the pathologist or EBE diagnosed an epithelial cyst, indicating results unlikely to occur by chance. CONCLUSION: The distinction of functional from epithelial ovarian cysts is best achieved by combining measurement of the tumor markers CEA and CA-125 with a high level of cytopathology experience.

Repeat cervical cytology at the time of colposcopy. Is there an added benefit?

OBJECTIVE: To determine if repeating the Pap smear (PS) at colposcopy offers added benefit in the detection of cervical squamous intraepithelial lesions (SILs). STUDY DESIGN: Eight hundred fifty-two women were subjects of this study. Patients with cervical SIL were defined as women with SIL on the repeat PS, or SIL on the colposcopic cervical biopsy (bx) or a negative repeat PS and bx but confirmed SIL on both the previous and follow-up PS or bx. The sensitivities of repeat PS and bx in detecting SIL were calculated. The chi 2 test was used to assess statistical significance. The total cost of repeating the PS was calculated by multiplying the total number of patients (852) by the estimated cost of a single PS ($25). RESULTS: The sensitivities of repeat PS, bx and PS/bx combined were .89, .69 and .92 for low grade SIL (LSIL) and .74, .77 and .98 for high grade SIL (HSIL), respectively (P < .0001). Sixteen percent of the HSIL and 28% of the LSIL cases were diagnosed on repeat PS only (negative bx). If repeat PS was omitted, $21,300 would have been saved.