Selumetinib in women with recurrent low-grade serous carcinoma of the ovary or peritoneum: an open-label, single-arm, phase 2 study.

BACKGROUND: Low-grade serous carcinoma of the ovary is chemoresistant but mutations in the MAPK pathway could be targeted to control tumour growth. We therefore assessed the safety and activity of selumetinib, an inhibitor of MEK1/2, for patients with this cancer. METHODS: In this open-label, single-arm phase 2 study, women (aged ≥18 years) with recurrent low-grade serous ovarian or peritoneal carcinoma were given selumetinib (50 mg twice daily, orally) until progression. The primary endpoint was the proportion of patients who had an objective tumour response according to RECIST version 1.1, assessed for all the treated patients. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00551070. FINDINGS: 52 patients were enrolled between Dec 17, 2007, and Nov 23, 2009. All were eligible for analyses. Eight (15%) patients had an objective response to treatment-one patient had a complete response and seven had partial responses. 34 (65%) patients had stable disease. There were no treatment-related deaths. Grade 4 toxicities were cardiac (one), pain (one), and pulmonary events (one). Grade 3 toxicities that occurred in more than one patient were gastrointestinal (13), dermatological (nine), metabolic (seven), fatigue (six), anaemia (four), pain (four), constitutional (three), and cardiac events (two). INTERPRETATION: Selumetinib is well tolerated, and is active in the treatment of recurrent low-grade serous carcinoma of the ovary or peritoneum. The findings suggest that inhibitors of the MAPK pathway warrant further investigation in these patients. FUNDING: National Cancer Institute.

A Rare Case of Blastic Plasmacytoid Dendritic Cell Neoplasm Occurred in Postchemotherapy of Breast Cancer.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and highly aggressive hematologic malignancy that arises from plasmacytoid dendritic cells. BPDCN typically presents with skin lesions and may involve peripheral blood, bone marrow, lymph nodes, or extranodal sites. It usually arises de novo, and some BPDCN cases are associated with or develop into myeloid neoplasms. Here, we report a case of a 57-year-old female presenting with cervical lymphadenopathy and skin rashes during the COVID-19 pandemic in 2021 following multiple types of postmastectomy therapy for breast cancer. The patient was ultimately diagnosed with BPCDN by lymph node biopsy. To the best of our knowledge, this is the first case report of BPDCN occurring postchemotherapy of breast cancer.

A modified Latent Class Model assessment of human papillomavirus-based screening tests for cervical lesions in women with atypical glandular cells: a Gynecologic Oncology Group study.

PURPOSE: In the absence of gold standard diagnoses, we estimate age-specific false-positive and false-negative prediction rates of HPV-, cytology-, and histology-based tests for significant cervical lesions (SCL) in US women with AGC-NOS Pap smear diagnoses. METHODS: Modified Latent Class Model (LCM) analyses, with prevalence of SCL modeled as a function of age, were applied to GOG-0171 study data (n = 122). The accuracies of several HPV-based tests, including Hybrid Capture II high-risk HPV (HC2 H-HPV); carbonic anhydrase IX (CA-IX); and invasive histological diagnosis, were compared. 1-PPV and 1-NPV were written as functions of sensitivity, specificity, and prevalence to obtain age-specific false-positive and false-negative rates. RESULTS: The histology-based test was nearly perfect (sensitivity = 1.00, CI = 0.98-1.00; specificity = 0.99, CI = 0.96-1.00). Otherwise, HC2 H-HPV performed best (sensitivity = 1.00, CI = 1.00-1.00; specificity = 0.87, CI = 0.79-0.94). The false-positive detection rates (1-PPV) for HC2 H-HPV were high (>17 %) at each age, while those of the histological diagnoses were low (<5 % at ages ≤60 and <17 % overall ages). False-negative prediction rates (1-NPV) for HC2 H-HPV were <0.11 % at each age and were uniformly lower than those of other tests, including the histology-based test (<0.25 %). CA-IX together with HC2 H-HPV did not improve performance. CONCLUSIONS: Women with negative HC2 H-HPV can safely forego invasive treatment (i.e., cone or LEEP biopsy, hysterectomy) in favor of observational follow-up. Additional biomarkers must be found for use in combination with HC2 H-HPV to reduce false-positive rates. This novel application of a modified LCM exemplifies methods for potential use in future cancer screening studies when gold standard diagnoses are not available.

Phase III Randomized Trial of Maintenance Taxanes Versus Surveillance in Women With Advanced Ovarian/Tubal/Peritoneal Cancer: A Gynecologic Oncology Group 0212:NRG Oncology Study.

PURPOSE: To compare taxane maintenance chemotherapy, paclitaxel (P) and paclitaxel poliglumex (PP), with surveillance (S) in women with ovarian, peritoneal, or fallopian tube (O/PC/FT) cancer who attained clinical complete response after first-line platinum-taxane therapy. METHODS: Women diagnosed with O/PC/FT cancer who attained clinical complete response after first-line platinum-taxane-based chemotherapy were randomly allocated 1:1:1 to S or maintenance, P 135 mg/m2 once every 28 days for 12 cycles, or PP at the same dose and schedule. Overall survival (OS) was the primary efficacy end point. RESULTS: Between March 2005 and January 2014, 1,157 individuals were enrolled. Grade 2 or worse GI adverse events were more frequent among those treated with taxane (PP: 20%, P: 27% v S: 11%). Grade 2 or worse neurologic adverse events occurred more often with taxane treatment (PP: 46%, P: 36% v S: 14%). At the fourth scheduled interim analysis, both taxane regimens passed the OS futility boundary and the Data Monitoring Committee approved an early release of results. With a median follow-up of 8.1 years, 653 deaths were reported; none were attributed to the study treatment. Median survival durations were 58.3, 56.8, and 60.0 months for S, P, and PP, respectively. Relative to S, the hazard of death for P was 1.091 (95% CI, 0.911 to 1.31; P = .343) and for PP, it was 1.033 (95% CI, 0.862 to 1.24; P = .725). The median times to first progression or death (PFS) were 13.4, 18.9, and 16.3 months for S, P, and PP, respectively. Hazard ratio = 0.801; 95% CI, 0.684 to 0.938; P = .006 for P and hazard ratio = 0.854; 95% CI, 0.729 to 1.00; P = .055 for PP. CONCLUSION: Maintenance therapy with P and PP did not improve OS among patients with newly diagnosed O/tubal/peritoneal cancer, but may modestly increase PFS. GI and neurologic toxicities were more frequent in the taxane treatment arms.

A Rare Case of Histiocytic Sarcoma Secondary to Gastrointestinal Stromal Tumor in the Stomach: Transdifferentiation or Synchronicity?

Histiocytic sarcoma is a rare malignant histiocytic neoplasm composed of cells with morphologic and immunophenotypic features of mature tissue histiocytes. It occurs anywhere in the body and behaves aggressively. However, its etiology is unknown. Here, we report a 68-year-old female who developed histiocytic sarcoma following chemotherapy with imatinib (Gleevec) for gastrointestinal stromal tumor. Possible mechanisms of transdifferentiation from gastrointestinal stromal tumor to histiocytic sarcoma are discussed based on the features of our case and other two similar cases in the literature.

Feasibility and potential significance of rapid in vitro qualitative phenotypic antimicrobial susceptibility testing of gram-negative bacilli with the ProMax system.

The emergence and evolution of antibiotic resistance has been accelerated due to the widespread use of antibiotics and a lack of timely diagnostic tests that guide therapeutic treatment with adequate sensitivity, specificity, and antimicrobial susceptibility testing (AST) accuracy. Automated AST instruments are extensively used in clinical microbiology labs and provide a streamlined workflow, simplifying susceptibility testing for pathogenic bacteria isolated from clinical samples. Although currently used commercial systems such as the Vitek2 and BD Phoenix can deliver results in substantially less time than conventional methods, their dependence on traditional AST inoculum concentrations and optical detection limit their speed somewhat. Herein, we describe the GeneFluidics ProMax lab automation system intended for a rapid 3.5-hour molecular AST from clinical isolates. The detection method described utilizes a higher starting inoculum concentration and automated molecular quantification of species-specific 16S rRNA through the use of an electrochemical sensor to assess microbiological responses to antibiotic exposure. A panel of clinical isolates consisting of species of gram-negative rods from the CDC AR bank and two hospitals, New York-Presbyterian Queens and Medical College of Wisconsin, were evaluated against ciprofloxacin, gentamicin, and meropenem in a series of reproducibility and clinical studies. The categorical agreement and reproducibility for Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, and Pseudomonas aeruginosa were 100% and 100% for ciprofloxacin, 98.7% and 100% for gentamicin and 98.5% and 98.5% for meropenem, respectively.

A Surgical Window Trial Evaluating Medroxyprogesterone Acetate with or without Entinostat in Patients with Endometrial Cancer and Validation of Biomarkers of Cellular Response.

PURPOSE: This surgical window of opportunity (window) study assessed the short-term effect of medroxyprogesterone acetate (MPA) alone versus MPA plus the histone deacetylase (HDAC) inhibitor entinostat on regulation of progesterone receptor (PR) in women with newly diagnosed endometrioid endometrial adenocarcinoma. PATIENTS AND METHODS: This multisite, randomized, open-label surgical window study treated women intramuscularly on day 1 with 400 mg MPA. Entinostat given 5 mg by mouth on days 1, 8, and 15 was randomly assigned with equal probability. Surgery followed on days 21-24. Pretreatment and posttreatment tissue was assessed for PR H-scores, Ki-67 levels, and histologic response. RESULTS: Fifty patients were accrued in 4 months; 22 and 20 participants had PR evaluable pretreatment and posttreatment slides in the MPA and MPA/entinostat arms, respectively. Median posttreatment PR H-scores were significantly lower than pretreatment H-scores in both arms but did not differ significantly (MPA: 247 vs. 27, MPA/entinostat 260 vs. 23, respectively, P = 0.87). Decreased Ki-67 was shown in 90% treated with MPA/entinostat compared with 68% treated with MPA alone (P = 0.13). Median PR H-score decreases were larger when Ki-67 was decreased (208) versus not decreased (45). The decrease in PR pretreatment versus posttreatment was associated with loss of Ki-67 nuclear staining, consistent with reduced cellular proliferation (P < 0.008). CONCLUSIONS: This surgical window trial rapidly accrued in a multisite setting and evaluated PR as its primary endpoint and Ki-67 as secondary endpoint. Despite no immediate effect of entinostat on PR in this short-term study, lessons learned can inform future window and treatment trials.

CXCR3 expression is associated with poor survival in breast cancer and promotes metastasis in a murine model.

Breast tumor cells express the chemokine receptor CXCR3, which binds the ligands CXCL9, CXCL10, and CXCL11. CXCR3 and other chemokine receptors may mediate tumor metastasis by supporting migration of tumor cells to sites of ligand expression including the lymph nodes, lungs, and bone marrow. We examined the relationship of CXCR3 expression to clinical outcome in 75 women diagnosed with early-stage breast cancer. We detected CXCR3 in malignant epithelium from all tumors. Twelve percent were weakly positive and 64% had moderate levels of CXCR3. Strong CXCR3-positive staining was observed in 24% of tumors. Kaplan-Meier survival curves showed that high CXCR3 expression was associated with poorer overall survival; the unadjusted hazard ratio was 1.56 and it was marginally significant (P=0.07). When interactions between lymph node status and CXCR3 were considered, the adjusted hazard ratio for CXCR3 was 2.62 (P=0.02) for women with node-negative disease at diagnosis, whereas the hazard ratio for CXCR3 was not significant for those with node-positive disease. CXCR3 gene silencing inhibited lung colonization and spontaneous lung metastasis from mammary gland-implanted tumors in a murine model. The size or growth rate of the locally growing tumors was not affected. The antimetastatic effect of CXCR3 gene silencing was compromised in mice depleted of Natural Killer cells or with mutations in IFN-gamma, suggesting that the role of CXCR3 is not simply to mediate tumor cell trafficking. These studies support the continued examination of CXCR3 as a potential therapeutic target in patients with breast cancer.

Extracranial Meningioma in the Scalp with Concurrent Steatocystoma.

This report documents a rare case of an extracranial meningioma on the posterior scalp without apparent dural connection. Additionally, a sebaceous steatocystoma of the anterior scalp presented alongside the meningioma. A steatocystoma localized to the scalp is also remarkably rare. To our knowledge, this is the first report documenting both an extracranial meningioma and a steatocystoma presenting concurrently on the scalp. A male patient in his thirties presented with a mass lesion on the scalp. A CT scan revealed one posterior scalp mass with no intracranial abnormalities. Post excision histologic examination confirmed an extracranial meningioma (meningothelial variant, WHO Grade I). A second anterior scalp mass, not revealed by CT scan, was discovered during surgery. It was excised and diagnosed as a steatocystoma. Meningiomas predominantly occur intracranially but, in some instances, may present as a standalone extracranial tumor without intracranial abnormalities. Because extracranial meningioma is uncommon, it may be overlooked during clinical diagnosis of scalp masses. We recommend that this neoplasm be routinely considered in the differential diagnosis of extracranial tumors. The discovery of another rare tumor-a steatocystoma located in immediate proximity on the scalp-is further remarkable. We briefly review relevant case reports and etiologies and consider a potential relationship between the two neoplasms. However, it remains more likely that the concurrence of these tumors in our patient was simply coincidental.

A Rare Case of Extracavitary Primary Effusion Lymphoma in the Bladder and Ureter.

Primary effusion lymphoma (PEL) is a rare and very aggressive large B-cell lymphoma usually presenting as serous effusions without a tumor mass. It is universally associated with human herpesvirus type-8 (HHV-8) infection. It most commonly occurs in the body cavities and rarely develops as solid tumor masses in the wall of cavity and other organs, and it has been termed as extracavitary PEL. Extracavitary PEL has been reported in the lymph nodes and extranodal sites. Here we report a rare case of extracavitary PEL occurring in the bladder and ureter of a human immunodeficiency virus (HIV)-negative 76-year-old Chinese male, presenting with right leg swelling, erythema, and pain. To the best of our knowledge, this is the first case of extracavitary PEL presenting in the bladder and ureter.

Carbonic anhydrase IX and human papillomavirus as diagnostic biomarkers of cervical dysplasia/neoplasia in women with a cytologic diagnosis of atypical glandular cells: a Gynecologic Oncology Group study in United States.

High-risk human papillomavirus (H-HPV) infection is strongly linked to cervical neoplasia, but its role in detecting glandular lesions (GLs) is unclear. In the cervix, carbonic anhydrase IX (CA-IX) is expressed in cervical neoplasia, but rarely in the benign cervix. The diagnostic utility of these biomarkers was evaluated in women with a cytologic diagnosis of atypical glandular cells (AGC). H-HPV was detected using hybrid capture 2 (HC2) in liquid-based cytology, and CA-IX immunoreactivity was studied on conventional Pap smears. Of 403 patients, 111 (28%) were positive for significant cervical lesions (SCLs) including CIN2, CIN3, adenocarcinoma in situ or invasive carcinoma. CA-IX testing alone (n = 403) had a sensitivity of 75, 95 or 65% for SCLs, significant GLs or squamous lesions (SLs), respectively, with a specificity of 88% and a false negative rate (FNR defined as 1 minus negative predictive value) of 10%. Testing for H-HPV (n = 122) had a sensitivity of 97, 100 or 96% for SCLs, GLs or SLs, respectively, with a specificity of 87% and a FNR of 1%. The combination of CA-IX and H-HPV testing (n = 122), collectively, had the same sensitivity, specificity and FNR for SCLs, GLs or SLs as H-HPV testing alone. The conclusions of our study are that both H-HPV and CA-IX testing are useful diagnostic markers for GLs. However, H-HPV testing is a better diagnostic marker for SLs. The combination of CA-IX with H-HPV testing does not improve the diagnostic accuracy for cervical neoplasia in women with AGC diagnosis over that of H-HPV testing alone.

A case report of parotid mammary analogue secretory carcinoma and reviews.

INTRODUCTION: Mammary analog secretory carcinoma (MASC) is a new diagnosis of head and neck tumors first reported in 2010. It was often misdiagnosed as salivary acinic cell carcinoma (AciCC). We present a patient with an asymptomatic parotid tumor that underwent deep lobe parotidectomy and postoperative radiation therapy. The final pathology showed MASC. CASE PRESENTATION: A 57-year-old male presented with an asymptomatic enlarging right parotid mass. A CT neck with IV contrast showed a 1.2 cm heterogeneously enhancing mass in the center of the right parotid gland without extraparotid extension. An FNA showed an epithelial neoplasm with papillary features. The patient underwent a right deep lobe parotidectomy with facial nerve dissection. The final pathology confirmed the diagnosis of MASC. He subsequently completed a 6-week course of radiation therapy and remained asymptomatic at his 30-month follow up. DISCUSSION/CONCLUSION: Although MASC is considered a low-grade tumor in most cases, recurrence and disseminated disease are not uncommon. No standard treatment protocol has been established. This report aims to enhance the awareness of this diagnosis and provide a review of current treatments for head and neck oncology care providers.

Phase II trial of cetuximab and carboplatin in relapsed platinum-sensitive ovarian cancer and evaluation of epidermal growth factor receptor expression: a Gynecologic Oncology Group study.

PURPOSE: This phase II trial assessed the activity and tolerability of cetuximab (C225, Erbitux) in combination with carboplatin in patients with relapsed platinum-sensitive ovarian or primary peritoneal carcinoma. PATIENTS AND METHODS: Patients were to receive combination therapy with cetuximab (initial dose of 400 mg/m2 intravenously on cycle 1, day 1, followed by weekly infusions of 250 mg/m2) and carboplatin (AUC of 6 on day 1 and every 3 weeks). The primary objectives of this trial were to estimate the anti-tumor activity and adverse events of this combination therapy. Immunohistochemical expression of EGFR was evaluated in tumor specimens from patients enrolled in this trial. RESULTS: Of the 29 patients, 28 (97%) were eligible and evaluable for analysis of the efficacy and toxicity of cetuximab administered in combination with carboplatin. Of the evaluable entries, 26 had EGFR-positive tumors and the response rate in this group of patients was as follows: 9 demonstrated an objective response (3 CR; 6 PR) and 8 had stable disease. The response rate did not meet criteria for opening a second stage of accrual. The median time to progression was 9.4+ months (range: .9-22.2+). The most commonly observed adverse events were dermatologic toxicity (grade 3 in 32%), thrombocytopenia (grade 3 in 14%), and hypersensitivity reactions (grade 3 and 4 in 18%). CONCLUSIONS: Cetuximab administered in combination with carboplatin had modest activity in screened patients with EGFR-positive, relapsed platinum-sensitive ovarian or primary peritoneal carcinoma. Cetuximab was associated with an acneiform rash in a majority of patients and occasional serious hypersensitivity reactions.

Phase III trial to evaluate the efficacy of maintaining hemoglobin levels above 12.0 g/dL with erythropoietin vs above 10.0 g/dL without erythropoietin in anemic patients receiving concurrent radiation and cisplatin for cervical cancer.

PURPOSE: To determine whether maintaining HGB levels > or = 12.0 g/dL with recombinant human erythropoietin (R-HUEPO) compared to "standard" treatment (transfusion for HGB < or = 10.0 g/dL) improves progression-free survival (PFS), overall survival (OS) and local control (LC) in women receiving concurrent weekly cisplatin and radiation (CT/RT) for carcinoma of the cervix. In addition, to determine whether platinum-DNA adducts were associated with clinical characteristics or outcome. METHODS: Patients with stage IIB-IVA cervical cancer and HGB < 14.0 g/dL were randomly assigned to CT/RT+/-R-HUEPO (40,000 units s.c. weekly). R-HUEPO was stopped if HGB > 14.0 g/dL. Endpoints were PFS, OS and LC. Platinum-DNA adducts were quantified using immunocytochemistry assay in buccal cells. RESULTS: Between 08/01 and 09/03, 109 of 114 patients accrued were eligible. Fifty-two received CT/RT and 57 CT/RT+R-HUEPO. The study closed prematurely, with less than 25% of the planned accrual, due to potential concerns for thromboembolic event (TE) with R-HUEPO. Median follow-up was 37 months (range 9.8-50.4 months). PFS and OS at 3 years should be 65% and 75% for CT/RT and 58% and 61% for CT/RT+R-HUEPO, respectively. TE occurred in 4/52 receiving CT/RT and 11/57 with CT/RT+R-HUEPO, not all considered treatment related. No deaths occurred from TE. High-platinum adducts were associated with inferior PFS and LC. CONCLUSION: TE is common in cervical cancer patients receiving CT/RT. Difference in TE rate between the two treatments was not statistically significant. The impact of maintaining HGB level > 12.0 g/dL on PFS, OS and LC remains undetermined.

Genetic deletions in sputum as diagnostic markers for early detection of stage I non-small cell lung cancer.

PURPOSE: Analysis of molecular genetic markers in biological fluids has been proposed as a powerful tool for cancer diagnosis. We have characterized in detail the genetic signatures in primary non-small cell lung cancer, which provided potential diagnostic biomarkers for lung cancer. The aim of this study was to determine whether the genetic changes can be used as markers in sputum specimen for the early detection of lung cancer. EXPERIMENTAL DESIGN: Genetic aberrations in the genes HYAL2, FHIT, and SFTPC were evaluated in paired tumors and sputum samples from 38 patients with stage I non-small cell lung cancer and in sputum samples from 36 cancer-free smokers and 28 healthy nonsmokers by using fluorescence in situ hybridization. RESULTS: HYAL2 and FHIT were deleted in 84% and 79% tumors and in 45% and 40% paired sputum, respectively. SFTPC was deleted exclusively in tumor tissues (71%). There was concordance of HYAL2 or FHIT deletions in matched sputum and tumor tissues from lung cancer patients (r = 0.82, P = 0.04; r = 0.84, P = 0.03), suggesting that the genetic changes in sputum might indicate the presence of the same genetic aberrations in lung tumors. Furthermore, abnormal cells were found in 76% sputum by detecting combined HYAL2 and FHIT deletions whereas in 47% sputum by cytology, of the cancer cases, implying that detecting the combination of HYAL2 and FHIT deletions had higher sensitivity than that of sputum cytology for lung cancer diagnosis. In addition, HYAL2 and FHIT deletions in sputum were associated with smoking history of cancer patients and smokers (both P < 0.05). CONCLUSIONS: Tobacco-related HYAL2 and FHIT deletions in sputum may constitute diagnostic markers for early-stage lung cancer.

Cytogenetic instability in ovarian epithelial cells from women at risk of ovarian cancer.

Fanconi anemia is an inherited cancer predisposition disease characterized by cytogenetic and cellular hypersensitivity to cross-linking agents. Seeking evidence of Fanconi anemia protein dysfunction in women at risk of ovarian cancer, we screened ovarian surface epithelial cells from 25 primary cultures established from 22 patients using cross-linker hypersensitivity assays. Samples were obtained from (a) women at high risk for ovarian cancer with histologically normal ovaries, (b) ovarian cancer patients, and (c) a control group with no family history of breast or ovarian cancer. In chromosomal breakage assays, all control cells were mitomycin C (MMC) resistant, but eight samples (five of the six high-risk and three of the eight ovarian cancer) were hypersensitive. Lymphocytes from all eight patients were MMC resistant. Only one of the eight patients had a BRCA1 germ-line mutation and none had BRCA2 mutations, but FANCD2 was reduced in five of the eight. Ectopic expression of normal FANCD2 cDNA increased FANCD2 protein and induced MMC resistance in both hypersensitive lines tested. No FANCD2 coding region or promoter mutations were found, and there was no genomic loss or promoter methylation in any Fanconi anemia genes. Therefore, in high-risk women with no BRCA1 or BRCA2 mutations, tissue-restricted hypersensitivity to cross-linking agents is a frequent finding, and chromosomal breakage responses to MMC may be a sensitive screening strategy because cytogenetic instability identified in this way antedates the onset of carcinoma. Inherited mutations that result in tissue-specific FANCD2 gene suppression may represent a cause of familial ovarian cancer.

Ruptured clear cell carcinoma of the ovary presenting as acute abdomen.

BACKGROUND: Ovarian cancer remains one of the leading causes of cancer-related deaths among women. Clear cell ovarian carcinoma is a rare histologic subtype accounting for 5-10% of all epithelial ovarian cancers and is often associated with endometriosis. Patients generally present with vague abdominal and pelvic complaints. However, patients can present in the acute setting with pleural effusions, ascites, bowel obstructions, and deep vein thrombosis. CASE: A 54 year old woman presenting with an acute abdomen secondary to rupture of ovarian clear cell carcinoma. CONCLUSION: Ovarian clear cell carcinoma should remain in the differential diagnosis in a patient presenting with an acute abdomen and imaging suspicious for a gynecologic malignancy originating from the ovary.

Impact of the new Bethesda System 2001 on specimen adequacy of conventional cervicovaginal smears.

The Bethesda System (TBS) 2001 workshop addressed the issue of specimen adequacy by recommending the elimination of the "satisfactory but limited by" category and its replacement by a semiquantitative method for assessing squamous cellularity. The purpose of this study is to compare the rate of unsatisfactory specimens of conventional cervicovaginal smears (CVS) before and after the implementation of the TBS 2001 recommendations. TBS 2001 recommendations were implemented in our laboratory on January 1st, 2002. Data were compared from conventional CVS evaluated 6 mo prior and 6 mo after the implementation of TBS 2001. The total number of conventional CVS for the second half of 2001 was 5,808, 21 of which were considered unsatisfactory for evaluation (0.36%). Fourteen of these 21 cases had a repeat CVS, one case was diagnosed as low-grade squamous intraepithelial lesion (LSIL), and one was inadequate. In contrast, there were 288 unsatisfactory CVS out of 5,459 cases (5.3%) in the first half of 2002. Of these, 154 CVS were repeated, five cases were designated as ASCUS, and three were LSIL. Twenty-one cases had a second inadequate diagnosis, eight of these were repeated and all were negative for intraepithelial lesion or malignancy. In our laboratory, the use of the new Bethesda System guidelines yielded more than a 10-fold increase in the rate of unsatisfactory conventional CVS. This led to numerous additional office visits to obtain a repeat CVS. Only eight repeat CVS identified epithelial cell abnormalities. The implications of our findings are that TBS 2001 guidelines regarding satisfactory conventional CVS result in increased healthcare cost without identifying a significant number of new epithelial cell abnormalities.

A rare case of fetal adenocarcinoma of the lung.

Fetal adenocarcinoma is a rare lung malignancy associated with improved outcomes compared to more common adenocarcinoma variants. We describe a case of a 31-year-old woman who presented with right-sided chest pain, and was subsequently diagnosed with an intermediate-grade stage IV fetal adenocarcinoma with chest wall invasion. She was treated with surgical resection and adjuvant radiation.

The usefulness of S100P, mesothelin, fascin, prostate stem cell antigen, and 14-3-3 sigma in diagnosing pancreatic adenocarcinoma in cytological specimens obtained by endoscopic ultrasound guided fine-needle aspiration.

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of the pancreas is an efficient and minimally invasive procedure for the diagnosis and staging of pancreatic adenocarcinoma. Because of some limitations of EUS-FNA in diagnosis of well-differentiated or early stage cancers, the purpose of this study is to assess the added benefit of immunohistochemistry. We studied five proteins overexpressed in pancreatic adenocarcinoma, namely, prostate stem cell antigen, fascin, 14-3-3 sigma, mesothelin and S100P utilizing immunohistochemistry on paraffin sections from cellblocks obtained by EUS-FNA. Sixty-two cases of EUS-FNA of the pancreas that had follow-up histological and/or clinical diagnosis and sufficient material in cell blocks were included. Using histological diagnosis and/or clinical outcome as the reference standard, EUS-FNA shows the highest sensitivity (95%) and specificity (91%) and is superior to any marker in this study. Among five antibodies, S100P reveals the best diagnostic characters showing 90% of sensitivity and 67% of specificity. Fascin shows high specificity (92%) but low sensitivity (38%). Mesothelin has a moderate sensitivity (74%) and low specificity (33%), PSCA and 14-3-3 show high sensitivity but zero specificity. S100P and mesothelin were useful in nine indeterminate cases. S100P correctly predicted six of seven cancers and one of one without cancer and mesothelin correctly diagnosed five of seven cancers and one of two noncancers in this group. EUS-FNA cytomorphology is superior to any of the immunohistochemical markers used in this study. Use of S100P and mesothelin in cytologically borderline cases can increase the diagnostic accuracy in this group.