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Introduction: Endobronchial ultrasound (EBUS)-guided transbronchial needle aspirate (TBNA) is a widely used method of minimally invasive lymph node sampling. The benefit of processing samples by cytologic methods versus "core biopsy" is unclear. It is unknown if safety or diagnostic yield varies by needle gauge., Materials and Methods: Between June 2018 and July 2019, 40 patients (56 lesions) undergoing EBUS TBNA lymph node evaluation were enrolled in this single-center prospective trial. Patients were chosen by permuted block randomization to undergo EBUS TBNA starting with 22-gauge (22g) or 19-gauge (19g) needles. Separate samples were sent for processing by cytologic methods and histopathology. Surgical pathologists and cytopathologists were blinded to needle size. The primary endpoint was diagnostic yield. Secondary endpoints compared specimen adequacy by rapid onsite evaluation (ROSE), sample adequacy for molecular testing, sample quality, and safety., Results: Diagnostic yield for histopathologic examination was 87.5% and 83.9% for 19g and 22g respectively (P = 0.625). There was no significant difference in diagnostic yield by cytologic examination based on needle size. There was no significant difference in slide quality. Molecular adequacy for core-biopsy was 77% and 80% for 22g and 19g needles, respectively. Molecular adequacy for cytology cell block was 77% and 80% for 22g and 19g needles, respectively. There were no significant procedural complications., Conclusion: Both the 22g and 19g EBUS TBNA needles provided a similar diagnostic yield and clinical utility for ancillary testing. Processing techniques by cytologic methods or "core biopsy" showed no significant impact in diagnostic yield or utility of molecular testing., (Copyright © 2021 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

We conducted a prospective ancillary study to the study of tamoxifen and raloxifene (STAR) trial involving 4 institutions to determine: (1) our ability to collect nipple aspirate fluid (NAF) in postmenopausal women taking medication to decrease breast proliferation and (2) NAF biomarkers associated with breast cancer. NAF was collected before and 6 months after starting treatment. Three biomarkers, cytology, fluid volume, and prostate-specific antigen (PSA), were analyzed. NAF was collected from 26 of 33 (79%) enrolled subjects at baseline. We were able to collect fluid in 84% of the subjects who produced NAF at baseline and returned for second aspiration after 6 months of treatment. In these women, cytology was unchanged in 85%, improved in 11%, and worsened in 4% of breasts. Median PSA increased from 37.5 to 112 ng/L after treatment. NAF volume did not significantly change. In conclusion, after treatment with tamoxifen or raloxifene, changes in both NAF cytology and PSA were generally favorable, consistent with their expected antiproliferative effective effect on the breast. Multiinstitutional clinical trials in postmenopausal women using NAF biomarkers as the primary endpoints are feasible.

Background: The aim of this prospective study was to assess predictive markers in nipple aspirate fluid (NAF) and pathologic nipple discharge (PND) collected prior to excisional breast biopsy, as well as clinical factors available prior to biopsy, with histopathologic results in women with a radiographically suspicious and/or palpable breast lesion., Methods: 208 NAF samples from 191 women were evaluated for the following candidate predictive proteins and cellular markers: prostate-specific antigen (PSA), human glandular kallikrein 2 (hK2), basic fibroblast growth factor (bFGF), S phase fraction (SPF), DNA index, and cytology. Clinical factors included whether or not the lesion was palpable, menopausal status, history of pregnancy, history of birth control or hormone replacement use, and PND., Results: Considering all women, bFGF (p=0.005) and SPF (0.031) were associated, and abnormal cytology approached an association (p=0.056) with the presence of breast cancer. Women with PND were less likely to have breast cancer (4 vs. 37%, p<0.001) or palpable lesions (10 vs.43%, p<0.001), were younger, had lower PSA levels (p=0.046), and were more likely to have atypical NAF cytology (p=0.002). Excluding PND, increased age, postmenopause (both p<0.01), high bFGF (p=0.004) and low PSA (p=0.05) were associated with cancer. The best breast cancer predictive model included cytology, bFGF, and age (88% sensitive and 57% specific). When the data were divided by menopausal status, the optimal models to predict breast cancer, which included NAF hK2 or PSA and age, were 100% sensitive and 41% specific in pre- vs. 93% sensitive and 12% specific in postmenopausal women., Conclusion: NAF and clinical biomarkers are sensitive predictors of whether a breast contains cancer, and may ultimately help guide treatment. Future studies to determine the optimal combination of predictive markers are warranted.

Objective: To evaluate the technique and complications of fine-needle aspiration biopsy (FNAB) for iris tumors., Design: Retrospective, nonrandomized, single-center case series., Participants: One hundred eyes of 100 patients with diagnostically challenging iris tumors evaluated with FNAB., Main Outcome Measures: Biopsy technique and complications., Results: Of more than 1400 patients referred with an iris tumor over a 24-year period, 100 underwent FNAB for diagnostic purposes. The median patient age was 44 years. The median basal dimension of the lesion was 9.0 mm and median thickness was 2.5 mm. A limbal entry with transaqueous approach parallel to the iris was used in 100% of patients. Entry was from the superotemporal (52%) or inferotemporal (42%) direction. Needle gauge size was 22 (9%), 25 (55%), 27 (25%), or 30 (9%), depending on the friability and vascularity of the tumor. Adequate tumor sample was achieved in 99 eyes (99%). At the time of FNAB, the only immediate complication was partial hyphema (34%). Two weeks after FNAB, persistent hyphema was found in 6 eyes (6%), requiring surgical washout in 1 patient. There were no cases of recurrent hyphema, vitreous hemorrhage, prolonged hypotony, lens damage, endophthalmitis, or extraocular tumor seeding. At mean follow-up of 5 years, there was no incident of tumor recurrence on the iris, along the needle tract, or on the corneal or epibulbar surface., Conclusions: Using our technique, FNAB for diagnostically challenging iris tumors can achieve high yield with relatively few complications.

Retinoids are effective growth modulators of human ovarian carcinoma cell lines. Their effects are mediated by nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs), which are transcriptional factors and members of the steroid/thyroid receptor superfamily. To our knowledge, until now, the cellular distribution of RAR proteins in human ovarian tumor specimens is unknown. This study provides new data on the differential cellular localization of RAR alpha protein in 16 serous adenocarcinomas originating from the ovaries, fallopian tubes, and the peritoneum. Using an affinity-purified antiserum specific for RAR alpha and a monoclonal antibody recognizing the full-length estrogen receptor molecule (clone 6F11), we performed immunohistochemistry on frozen tissue sections and examined the relationship between RAR alpha and estrogen receptor protein expression by comparing the percentage of immunostained tumor cells for either receptor. Our findings indicate a strong linear relationship between the percentages of RAR alpha- and estrogen receptor-labeled tumor cells as determined by linear regression analysis (P < 0.005, r = 0.825). A modest inverse relationship was found between the percentage of RAR alpha-positive tumor cells and histological grade, attesting to a differentiation-dependent trend (P < 0.04). No significant relationship was found between RAR alpha-labeled cells and clinical stage (P = 0.139), site of tumor origin (ovaries versus fallopian tubes versus peritoneum) (P = 0.170), and primary versus metastatic lesion (P = 0.561). Thus, serous adenocarcinomas are capable of expressing RAR alpha and estrogen receptor despite high histological grade and advanced stage of neoplastic disease. Compared with the heterogeneous localization of RAR alpha in cancer cells, there was widespread RAR alpha immunoreactivity in tumor-infiltrating lymphocytes, vascular endothelial cells, and stromal fibroblasts, underscoring the value of immunohistochemistry in the accurate determination of RAR/(RXR) content in tumor specimens.

Background: Retinal astrocytic hamartoma and retinoblastoma may be very similar clinically, and their differentiation in atypical cases can be difficult, even with the use of ancillary methods such as fluorescein angiography, ultrasonography, and computed tomography. To the authors knowledge, fine-needle aspiration biopsy has not been used to diagnose astrocytic hamartoma in such cases., Patients and Methods: A 7-week-old boy had a minimally calcified retinal mass in the macular area of the left eye associated with an extensive secondary retinal detachment. The differential diagnosis included retinal astrocytic hamartoma and retinoblastoma. A transvitreal fine-needle aspiration biopsy was performed., Results: The cytology of the needle biopsy showed benign spindle and stellate cells, which were compatible with glial cells. The lesion had immunoreactivity for glial fibrillary acidic protein, further supporting the diagnosis of astrocytic tumor., Conclusion: Fine-needle aspiration biopsy is diagnostically useful in unusual cases where the differential diagnosis between retinoblastoma and astrocytic hamartoma is difficult.

Background: Fine-needle aspiration biopsy recently has been used as a diagnostic modality for selected intraocular tumors and simulating conditions. However, the value of fine-needle aspiration biopsy for intraocular tumors previously has not been clarified., Methods: Transocular fine-needle aspiration biopsy was performed on selected patients who had intraocular lesions that were suspected clinically to be neoplasms but in which there was diagnostic uncertainty based on noninvasive clinical evaluation. These cases were analyzed to determine accuracy, complications, and limitations of the technique., Results: Of 6500 patients referred to the Oncology Service for evaluation of possible intraocular tumor, transocular fine-needle aspiration biopsy was used clinically in 159 cases (2.4%). It proved to be a reliable diagnostic method for intraocular malignancies such as uveal melanoma, uveal metastasis, retinoblastoma, lymphoma, and leukemia. In the 140 cases (88%) in which adequate cytologic material was obtained, the sensitivity rate was 100% and the specificity rate was 98%. In 19 cases where the cytologic material was too scant to render a diagnosis, the sensitivity rate was 84% and the specificity rate was 98%. The problem of insufficient material for cytologic diagnosis has been greatly minimized with the recent use of a 22-gauge needle. The main complication was localized intraocular hemorrhage. Retinal detachment and tumor recurrence have not been observed., Conclusions: Transocular fine-needle aspiration biopsy is a safe and reliable diagnostic method for suspected intraocular tumors and inflammatory conditions in which noninvasive diagnostic modalities have failed to establish the diagnosis and in which cytologic verification of the diagnosis is necessary to institute appropriate treatment. Although the authors have had few complications with fine-needle aspiration biopsy, the technique should be reserved for selected cases where the diagnosis has not been established by less-invasive diagnostic measures.