Diagnostic Confirmation of Choroidal Lymphoma by Anterior Chamber Paracentesis and Aqueous Fluid Flow Cytometry.

PURPOSE: To report the clinical course of patients with diagnostic confirmation of choroidal lymphoma by anterior chamber paracentesis and aqueous fluid flow cytometry. METHODS: Single-center case series. RESULTS: Two patients with choroidal thickening were suspected to have choroidal lymphoma based on clinical findings and ultrasonographic evidence of extrascleral extension. In each case, anterior chamber paracentesis was performed due to the observation of the associated anterior chamber reaction. Flow cytometry detected the presence of a clonal B-cell population consistent with non-Hodgkin's lymphoma. In one case, external beam radiation therapy resulted in a complete therapeutic response. More invasive methods of ocular tissue biopsy were avoided. CONCLUSIONS: Definitive diagnosis in suspected cases of choroidal lymphoma remains challenging. Ocular fluid sampling may be a low morbidity and convenient alternative for confirming a suspected diagnosis in cases associated with cellular infiltration of the intraocular fluids.

Hemorrhagic choroidal detachment as the presenting sign of uveal melanoma.

PURPOSE: To describe two cases of medium-sized uveal melanoma presenting with hemorrhagic choroidal detachments. OBSERVATIONS: The first case is a 39-year-old man who presented with choroidal hemorrhage and angle closure glaucoma. The second case is a 42-year-old man who presented with choroidal hemorrhage and posterior scleritis. Vitrectomy with transvitreous fine needle aspiration biopsy was ultimately required to diagnose malignant uveal melanoma in each case. CONCLUSIONS AND IMPORTANCE: Intraocular hemorrhage is a rare presenting sign of uveal melanoma. When it does occur, it is typically associated with large tumors. Hemorrhagic choroidal detachments are particularly rare in uveal melanoma, and can limit the diagnostic utility of clinical exam, B-scan ultrasonography, and magnetic resonance imaging. Although it is uncommon, it is important to maintain a high index of suspicion for choroidal melanoma in any patient with unexplained choroidal hemorrhage.

Effect of Human Papillomavirus Vaccine to Interrupt Recurrence of Vulvar and Anal Neoplasia (VIVA): A Trial Protocol.

Importance: Human papillomavirus (HPV), particularly HPV type 16, causes most anal and vulvar high-grade squamous intraepithelial lesions (HSIL), which are precursors to cancer. After initial treatment of HSIL, more than 30% of patients will have disease recurrence, with even higher recurrence among HIV-positive individuals and men who have sex with men. Recurrences can be debilitating and lead to significant morbidity and medical expense. Observational studies suggest a possible therapeutic benefit of the licensed HPV vaccines in reducing recurrent lesions in previously infected persons. Objective: To test whether the licensed prophylactic HPV vaccine (Gardasil-9) can reduce the risk of HSIL recurrence by 50% in previously unvaccinated individuals recently treated for anal or vulvar HSIL. Design, Setting, and Participants: This is a trial protocol for a randomized, double-blind, placebo-controlled, proof-of-concept clinical trial. Eligible participants are aged 27 to 69 at study start and have not received prior HPV vaccination, have had anal or vulvar HSIL diagnosed on or after January 1, 2014, and have no evidence of HSIL recurrence at screening. Persons infected with HIV are eligible for the study provided they are receiving antiretroviral therapy. Target enrollment is 345 individuals. The primary outcome is time to histopathologically confirmed recurrence of HSIL. Differences in the risk for recurrence of HSIL will be evaluated using Cox proportional hazard models. Additional analyses include (1) frequency of HSIL recurrence; (2) role of HPV antibodies in deterring recurrence; (3) role of HPV persistence in recurrence, as measured by HPV genotype or HPV-16 variant lineage determined using swab samples collected at months 0, 18, and 36; and (4) incidence of adverse events. The study will be conducted at the University of Washington Virology Research Clinic from 2017 through 2022. Participants will be followed up for up to 36 months in the clinic, and up to 42 months by telephone. Discussion: Management of persistent or rapidly recurring anogenital HSIL remains challenging. Results from this study will provide evidence on whether incorporating the nonavalent HPV vaccine into routine care can decrease recurrence of anal and vulvar HSIL. Trial Registration: ClinicalTrials.gov identifier: NCT03051516.

Hepatic Lesions in a Cirrhotic Liver: Primary or Metastases?

Although prior studies showed that patients with cirrhosis have a lower risk of developing liver metastases, appropriate workup of incidental liver masses in cirrhotic liver is important for a correct diagnosis. Here we present a case of newly diagnosed liver cirrhosis with multifocal hepatic lesions, which was initially categorized as a LI-RADS (Liver Imaging Reporting and Data System) 5 lesions. Scintigraphy with 111In-pentetreotide (Octreoscan) indicated a suspected thyroid nodule, later confirmed to represent medullary thyroid carcinoma lesion. The most relevant imaging finding of this rare form of thyroid malignancy is reviewed in this presentation.

The outcomes of "atypical" and "suspicious" bile duct brushings in the identification of pancreaticobiliary tumors: Follow-up analysis of surgical resection specimens.

BACKGROUND: Bile duct brushing cytology is frequently used to investigate suspected pancreaticobiliary tumors, but it is associated with low diagnostic sensitivity. As recently proposed by the Papanicolaou Society of Cytopathology in its new classification scheme for pancreaticobiliary cytology, the use of "atypical" and "suspicious (for malignancy)" categories may give a better prediction of malignancy and improve patient management. METHODS: A series of 65 "atypical" and "suspicious" results initially diagnosed at the University of Washington and Harborview Medical Centers between 2005 and 2012 were analyzed to determine outcomes based on the review of subsequent surgical resection specimens. RESULTS: Seven of 15 (47%) "atypical" cases demonstrated malignant outcomes, whereas 49 of 50 (98%) "suspicious" cases showed documented malignancy within a mean follow-up of 4 months (P < 0.0001 from Pearson's chi-squared test). The analysis of surgical resection specimens demonstrates that 59% of "atypical" and "suspicious" bile duct brushings with malignant outcomes were pancreatic adenocarcinoma (95% confidence interval (CI): 46-71%), 97% of pancreatic adenocarcinomas caused strictures in the head of the pancreas (95% CI: 86-100%), and that 86% of pancreatic adenocarcinomas were moderate to poorly differentiated (95% CI: 73-99%). Fifty-three of the 60 (88%) patients in the presence of prior stenting had a histologically confirmed malignancy. CONCLUSION: The use of "atypical" and "suspicious" categories may allow more accurate surveillance and/or more rapid surgical exploration of pancreaticobiliary tumors.

Metastatic cutaneous melanoma to the ciliary body in familial atypical mole-melanoma (fam-m) syndrome.

PURPOSE: To report a case of metastatic melanoma to the ciliary body in familial atypical mole-melanoma syndrome. METHODS: Retrospective case report. PATIENTS: A 46-year-old woman presented with a ciliary body melanoma and tumor seeding of the anterior chamber structures. RESULTS: Biopsy and systemic workup suggested metastatic origin. CONCLUSIONS: Correlation is noted between the noncohesive epithelioid cell type and seeding of the anterior chamber.

Diagnostic value of unusual gross appearance of aspirated material from endoscopic ultrasound-guided fine needle aspiration of pancreatic and peripancreatic cystic lesions.

OBJECTIVE: To evaluate the diagnostic value of the gross appearance of aspirated material from endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of pancreatic orperipancreatic cystic lesions. STUDY DESIGN: This study focuses on nonneoplastic (peri)-pancreatic cystic lesions on EUS-FNA. Eight cases were identified with distinct gross appearances of aspirated material by the authors' experience and by computerized review. Gross observations are evaluated together with clinical data, radiologic findings, laboratory markers and cytologic and surgical microscopy findings. RESULTS: Aspiration of cystic lesions often results in nonspecific cytologic findings. Gross and microscopic appearance of aspirated material can provide valuable information. We divide findings of 8 cystic lesions into 3 different patterns according to their gross appearance at on-site EUS-FNA: Pattern 1, 2 cases of biloma; Pattern 2, 1 case of lymphoepithelial cyst with sebaceous differentiation; Pattern 3, 3 cases of regular lymphoepithelial cysts and 2 cases ofpancreatic pseudocyst. CONCLUSION: The full value of FNA is achieved only with the integrated approach, including the gross appearance of the cytology specimens. Certain unusual gross appearances of the aspirated material can add valuable information toward a pathologic diagnosis.

Vaginal, endometrial, and reproductive hormone findings: randomized, placebo-controlled trial of black cohosh, multibotanical herbs, and dietary soy for vasomotor symptoms: the Herbal Alternatives for Menopause (HALT) Study.

OBJECTIVE: To evaluate vaginal, endometrial, and reproductive hormone effects of three herbal regimens compared with placebo and hormone therapy (HT). DESIGN: This was a 1-year, randomized, double-blind, placebo-controlled trial of 351 women, ages 45 to 55, with two or more vasomotor symptoms per day. Women were randomly assigned to (1) black cohosh, (2) a multibotanical containing black cohosh, (3) the same multibotanical plus dietary soy counseling, (4) HT, or (5) placebo. Women were ineligible if they had used HT in the previous 3 months or menopausal herbal therapies in the previous month. Data on vaginal cytology and dryness were collected (at baseline and 3 and 12 mo). Daily menstrual diaries were maintained by 313 women with a uterus, and abnormal bleeding was evaluated. Serum estradiol, follicle-stimulating hormone, luteinizing hormone, and steroid hormone-binding globulin were assessed (baseline and 12 mo) among 133 postmenopausal women. Gynecologic outcomes of the five groups were compared. RESULTS: The five groups did not vary in baseline vaginal cytology profiles, vaginal dryness, menstrual cyclicity, or hormone profiles. The HT group had a lower percentage of parabasal cells and vaginal dryness than the placebo group at 3 and 12 months (P < 0.05). Abnormal bleeding occurred in 53 of 313 (16.9%) women. There were no differences in frequency of abnormal bleeding between any of the herbal and placebo groups, whereas women in the HT group had a greater risk than those in the placebo group (P < 0.001). Among postmenopausal women, HT significantly decreased follicle-stimulating hormone and increased estradiol; none of the herbal interventions showed significant effects on any outcomes at any time point. CONCLUSION: Black cohosh, used alone or as part of a multibotanical product with or without soy dietary changes, had no effects on vaginal epithelium, endometrium, or reproductive hormones.

Biliary brush cytology and the detection of cholangiocarcinoma in primary sclerosing cholangitis: evaluation of specific cytomorphologic features and CA19-9 levels.

Interpreting biliary brush cytology (BBC) findings in primary sclerosing cholangitis (PSC) is problematic. In our study, BBC findings and CA19-9 serum levels were evaluated for their effectiveness in diagnosing cholangiocarcinoma in patients with PSC. We reviewed 107 biliary brushings from 51 patients with PSC and concurrent CA19-9 levels between January 1995 and March 2004 at the University of Washington Medical Center, Seattle. A portion of the brushings were evaluated and scored according to specific cytologic criteria; statistical analysis showed which criteria were most predictive in diagnosing malignancy: nuclear/cytoplasmic ratio, prominent nucleoli, nuclear membrane irregularities, and discohesion were significant predictive features. Sensitivity and specificity of BBC were 62.5% and 100%, respectively. Sensitivity and specificity of CA19-9 at a cutoff of 186 IU/mL were 100% and 94%, respectively. BBC is a specific and relatively sensitive method of detecting cholangiocarcinoma, even in patients with PSC, especially when certain cytomorphologic features are identified. Combining biliary cytology and CA19-9 levels might have an important diagnostic role in PSC.

Intracervical sonographic-pathologic correlation: preliminary results.

OBJECTIVE: To determine whether current-generation endoluminal ultrasonic transducer technology could visualize dysplastic and malignant cervical lesions. METHODS: Inclusion criteria for patients enlisted in the study were abnormal Papanicolaou test results, an abnormality seen at colposcopy, and consent for a cone biopsy. In addition, we included 4 women who were undergoing hysterectomy but had no evidence of cervical abnormalities at the time of surgery, for a total of 28 women. We used a 20-MHz annular array intravascular transducer. We correlated all sonographic and pathologic results with regard to being normal or abnormal using the Pearson product moment correlation coefficient, and we evaluated interobserver variation by having 5 blinded sonologists interpret each examination and calculating kappa statistics. RESULTS: We performed intracervical sonography on 24 women with abnormal Papanicolaou test results and on 4 women without abnormalities. Nineteen of the 24 women with proven disease had abnormal sonographic images. Five women with pathologically proven cervical intraepithelial neoplasia I had normal sonographic images. Lesions ranged in size from 0.3 to 7 mm. Two carcinomas (5 and 7 mm diameter), multiple nabothian cysts, cervicitis, and 2 giant cell foreign body reactions were visible on sonography. The correlation coefficient for abnormal sonographic and pathologic findings was 0.87 (P < .005). We obtained a kappa value of 0.75 for interobserver variation. CONCLUSIONS: Intracervical sonography was able to visualize dysplastic lesions and carcinomas as hypoechoic defects with surrounding echogenic areas of glandular cervical mucosa. Lesions were shown with sufficient resolution and interobserver variation to suggest that the technique may be clinically applicable, particularly for planning surgical therapy. However, design of a transducer that can be easily sterilized between examinations, similar to current endovaginal probes, would be necessary to make intracervical sonography a clinically feasible examination.

The efficacy of reprocessing unsatisfactory cervicovaginal ThinPrep specimens with and without glacial acetic acid: effect on Hybrid Capture II human papillomavirus testing and clinical follow-up.

We sought to determine the efficacy of remaking initially unsatisfactory cervicovaginal ThinPrep (Cytyc, Boxborough, MA) specimens with and without the addition of glacial acetic acid (GAA) and the effect on human papilloma virus (HPV) Hybrid Capture II (HC2; Digene, Gaithersburg, MD) testing. A total of 583 initially unsatisfactory ThinPrep slide preparations were identified, and remakes were made with the residual in the PreservCyt (Cytyc) vials with (n = 455) or without (n = 128) GAA. Clinical follow-up information was obtained. The addition of GAA resulted in a 56.5% reduction in unsatisfactory cases, compared with a 26.6% reduction without GAA. Neoplasia and atypia were detected in the reprocessed specimens. The addition of GAA resulted in false-positive HC2 test results in 10 of 10 cases. Neutralization of the specimen may reverse this effect. Reprocessing unsatisfactory ThinPrep specimens with GAA can substantially reduce the overall unsatisfactory rate and result in the detection of significant lesions. However, the addition of GAA can result in false-positive results on HC2 HPV tests.

Unexpected gynecologic neoplasms in patients with proven or suspected BRCA-1 or -2 mutations: implications for gross examination, cytology, and clinical follow-up.

Identification of inheritable mutations associated with the development of malignancy has led to prophylactic surgeries to remove tissues at risk. We report seven unrelated patients with family histories of breast and/or ovarian cancer, five of whom underwent prophylactic salpingo-oophorectomy with hysterectomy. Four had proven BRCA-1 or -2 mutations. Malignant cells were found unexpectedly in the peritoneal washings of two patients, leading to the discovery of early-stage fallopian tube carcinoma. After changing the sampling technique at our institution, two more cases of unexpected fallopian tube carcinoma in situ were discovered. Another patient had a significant family history and underwent hysterectomy for uterine fibroids, leading to the discovery of fallopian tube carcinoma. Another patient with BRCA-1 mutation had unexpected widespread primary peritoneal papillary serous adenocarcinoma. The final patient had a borderline malignant clear cell adenofibroma. These cases underscore the importance of peritoneal cytology and thorough sampling in the management of patients undergoing hysterectomy with a family history of breast/ovarian cancer and/or known BRCA-1/BRCA-2 mutations. As prophylactic surgeries are becoming more common secondary to advances in molecular diagnostics, pathologists need to be aware that surgical specimens from these patients may require more rigorous examination to uncover early neoplastic changes.