Instrument Gauge and Type in Uveal Melanoma Fine Needle Biopsy: Implications for Diagnostic Yield and Molecular Prognostication.

PURPOSE: To systematically evaluate and compare the effects of using small-gauge needles and vitrectors on the ability to obtain adequate diagnostic and prognostic uveal melanoma biopsy specimens. DESIGN: Comparative evaluation of biopsy instruments. METHODS: Survival of uveal melanoma cells was evaluated in vitro following needle aspiration. Five therapeutically enucleated eyes were sampled in triplicate for ex vivo diagnostic biopsy experiments with 25 gauge (25 G) needle, 27 gauge (27 G) needle, and 27 G vitrector. During surgery in 8 patients, paired diagnostic transscleral fine needle aspiration biopsies were performed using both 25 G and 27 G needles. A review of cytologic specimens was performed by a panel of 3 expert cytopathologists. A retrospective chart review was performed to evaluate 100 consecutive tumors undergoing prognostic biopsy for gene expression profiling to assess the relationship between needle gauge and prognostic adequacy. RESULTS: No significant cell shearing of uveal melanoma cells occurred in vitro with 25 G, 27 G, or 30 G needles. For ex vivo biopsy samples, diagnostic yield was 100% using 25 G needle (5/5) or 27 G vitrector (5/5) but 60% using a 27 G needle (3/5). For in vivo samples, no difference in diagnostic yield was found between 25 G (75%, 6/8) or 27 G (75%, 6/8) needle sizes. Of 100 molecular prognostic biopsy samples evaluated, 65 were obtained using 27 G needles; for these biopsies, the prognostic yield was 65/65 (100%). CONCLUSIONS: For diagnostic biopsy of uveal melanoma, a larger-gauge needle or a 27 G vitrector may have better overall cellularity and diagnostic yield when compared to a 27 G needle. However, for much more common molecular prognostic testing, a 27 G needle provided adequate sample in 100% (65/65) of cases, and a larger needle provided no additional benefit.

Lymphoepithelioma-like carcinoma of the endometrium: immunophenotypic characterization of a rare tumor with microsatellite instability testing.

This report describes the clinicopathologic features of a primary lymphoepithelioma-like carcinoma of the endometrium, representing only the fourth reported case of this tumor at this location. In addition to its classic morphologic features, focal clear cells were also identified within the tumor, thereby expanding the morphologic spectrum of the neoplasm at this location. A comprehensive immunohistochemical characterization of the tumor was performed, as was microsatellite instability testing. The tumor was diagnosed in a 79-year-old woman and was surgically/pathologically staged as IB by the International Federation of Gynecology and Obstetrics (FIGO) criteria. The tumor displayed typical morphologic features (tumor cells with a syncytial appearance in an inflammatory background) with the exception of the aforementioned polygonal cells with well-defined cell membranes and cytoplasmic clarity in <1% of the tumor. The epithelial component showed strong and diffuse immunoreactivity for CAM 5.2, p53, p16, E-cadherin, cytokeratin (CK) 7, vimentin, CKAE1/3, and epithelial membrane antigen. The MIB-1 proliferative index in these regions was about 70%. Approximately 10% to 30% of lesional cells showed strong immunoreactivity for CK903, S100, MOC31, CD138, but the pattern of positivity was patchy and discontinuous. The epithelial cells were entirely negative for CK5/6, smooth muscle actin, p504S, CK20, synaptophysin, chromogranin, CD56, CD99, WT-1, thyroid transcription factor-1, p63, CD117 (c-kit), CD34, calretinin, desmin, estrogen receptor, progesterone receptor, FLI-1, ALK-1, D2-40, cytomegalovirus antigen, Epstein-Barr virus-encoded RNA-1, Epstein-Barr virus, monoclonal carcinoembryonic antigen, and HER2/neu. The foci with clear cells were not immunophenotypically distinct from the non-clear cell areas and had an approximately similar proliferative index. The inflammatory component was mixed (lymphocytes, histiocytes, plasma cells, neutrophils) but was composed predominantly of CD45/CD3/CD8 T lymphocytes, with a CD3 to CD20 ratio of approximately 10:1 and CD8 to CD4 T-cell ratio of approximately 3:1. Numerous (>100 positive cells per 10 high-power fields) S100-positive tumor-infiltrating Langerhans cells were present. The tumor DNA did not exhibit microsatellite instability at any of the loci analyzed. In summary, the limited data available suggest that lymphoepithelioma-like carcinoma is a distinct histotype of endometrial carcinoma that is typically seen in postmenopausal women, seems to be unrelated to the Epstein-Barr virus, and has an uncertain prognosis. Differential diagnostic and pathogenetic considerations are discussed within the context of the lesional morphologic and immunophenotypic profile as described herein and in previously reported cases.

Primary leiomyosarcoma of extragnathic bone: clinicopathologic features and reevaluation of prognosis.

CONTEXT: Leiomyosarcoma most commonly involves the female genital tract and occasionally arises within the retroperitoneum, abdominal cavity, or the soft tissues of the extremity. Presentation as a primary bone tumor is extraordinarily uncommon, potentially leading to misdiagnosis. The prognosis is traditionally thought to be dismal. However, this conclusion is largely based on individual case reports and small series, in some of which the pathologic diagnosis is not well documented. OBJECTIVE: To review the clinicopathologic features of well-established cases of primary skeletal leiomyosarcoma and reevaluate the prognostic implications thereof. DATA SOURCES: A National Center for Biotechnology Information PubMed search of the English language literature identified 104 authenticated cases of primary leiomyosarcoma of extragnathic bone. An additional 3 cases are reported and illustrated herein. CONCLUSIONS: Approximately half of all patients with primary skeletal leiomyosarcoma either presented with metastatic disease or developed metastases within 1 year of diagnosis. The 5-year overall and disease-free survival rates were 59% and 41%, respectively, comparable to that of other skeletal sarcomas. As for other bone and soft tissue sarcomas, high histologic grade and tumor stage are predictive of poor outcome.

Evaluation of a Digene-recommended algorithm for human papillomavirus low-positive results present in a "retest zone".

The Digene Hybrid Capture 2 (hc2) high-risk human papillomavirus (HPV) DNA test (Digene, Gaithersburg, MD) is widely used for triage of women with atypical squamous cells of undetermined significance. Results in a "retest zone" (weakly positive tests) are repeated up to 2 times according to the Digene-recommended algorithm. We studied 56 cervical samples in the retest zone. Specimens were tested by a multiplex polymerase chain reaction (PCR)-based genotyping assay, and relevant cytopathologic results were reviewed. Digene results were compared with a reference standard that combined PCR genotyping and cytopathology results. The first repeated Digene assay yielded a sensitivity of 85.2% and a specificity of 62.1% with false-positive and false-negative rates of 40.0% and 15.4%, respectively. The 22 negative samples underwent a second retest and 18 (82%) were negative by the reference standard. The combined first and second retest sensitivity, specificity, and predictive values remained unchanged from the first retest alone. Repeating specimens in the retest zone is necessary, but a second retest does not offer advantages over the first retest.

Retroperitoneal fibrosis secondary to actinomycosis with no intrauterine device.

BACKGROUND: Actinomycotic pelvic infection usually occurs in the presence of an intrauterine device. It can result in pelvic inflammatory disease, tubo-ovarian abscess, and retroperitoneal fibrosis. CASE: A 35-year-old multipara who had never used an intrauterine device presented with a 5-month history of progressively worsening, colicky, right-sided abdominal pain, dysuria, weight loss, and constipation. She was found to have retroperitoneal fibrosis. The diagnosis of actinomycotic pelvic infection was made at laparotomy. CONCLUSION: Actinomycosis may be considered in the differential diagnosis of women with retroperitoneal fibrosis, even when there is no history of an intrauterine device.