Analysis of endometrial carcinoma associated with tamoxifen exposure
Utility of extended pattern prostate biopsies for tumor localization
Grading of invasive cribriform carcinoma on prostate needle biopsy
Endometrial carcinoma and endometrial intraepithelial neoplasia classification of endometrial biopsies
Interobserver and intraobserver variation among experts in the diagnosis of thyroid follicular lesions
Liposarcoma: outcome based on the Scandinavian Sarcoma Group register
Tamoxifen is increasingly being used to treat and prevent breast cancer. Tamoxifen has been associated with increased risk of endometrial carcinoma, although the exact mechanism of action is unknown. The authors conducted a study to determine if there is a correlation between endometrial carcinoma, tamoxifen exposure, and microsatellite instability (MSI), PTEN, ®-catenin, and K-ras abnormalities. They selected a group of 18 patients with endometrial carcinoma following treatment with tamoxifen. A control group included 15 patients with endometrial carcinoma and associated ovarian hyperthecosis and one patient with endometrial carcinoma and adult granulosa cell tumor of the ovary. The latter was chosen because both conditions are associated with increased production of estrogen and increased risk of endometrial carcinoma. The second control group included 27 randomly selected consecutive patients with endometrial carcinoma without identifiable associated conditions. Immunostaining for ®-catenin was performed on all cases; DNA was extracted and amplified by polymerase chain-reaction with primers for ®-catenin, K-ras, and PTEN genes. BAT-25 and BAT-26 were analyzed to assess for microsatellite instability. There were 16 endometrioid endometrial carcinomas, one mixed carcinoma, and one clear cell carcinoma among patients in the tamoxifen group. All patients with ovarian hyperthecosis and adult granulosa cell tumor had endometrioid endometrial carcinoma. In the random control group, there were 26 endometrial carcinomas and one carcinosarcoma. Immunohistochemical and mutational analysis for ®-catenin showed abnormalities in four of 11 (36 percent) and three of 10 (30 percent) informative cases in the tamoxifen group; seven of 16 (44 percent) and four of 15 (27 percent) informative cases, respectively, in the ovarian hyperthecosis group; and one of 27 (four percent) random control cases (P<.05). Patients with tamoxifen exposure had more K-ras mutations, fewer PTEN mutations, and less MSI than controls, but the results were not statistically significant. The authors concluded that a direct relationship exists between tamoxifen exposure and overexpression of ®-catenin oncoprotein, which is known to play a major role in the pathogenesis of estrogen-driven, type I endometrial adenocarcinoma.
Turbiner J, Moreno-Bueno G, Dahiya S, et al. Clinicopathological and molecular analysis of endometrial carcinoma associated with taxoxifen. Mod Pathol. 2008;21:925–936.
Correspondence: Dr. J. Turbiner at email@example.com
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Focal targeted therapies have been proposed as a treatment for localized prostate cancer. However, these modalities rely heavily on accurate tumor localization to achieve total tumor ablation. The authors conducted a study to examine the ability of contemporary extended-pattern prostate biopsy to predict the location of tumors. They evaluated 281 men with prostate cancer with at least 12 cores detected via a standardized extended-pattern biopsy template who subsequently underwent radical prostatectomy. Tumor location on biopsy, stratified by laterality and site (apex versus mid-base prostate), was compared with corresponding locations on the prostatectomy specimen. Generalized estimating equation models were developed to assess the effects of clinical variables on pathologic agreement between biopsy and prostatectomy specimens. For the 281 prostate biopsies, the positive predictive value of right and left needle biopsy was high at 97.3 percent and 96.7 percent, respectively. However, the negative predictive value was low at 24.7 percent and 31.3 percent, respectively. When more specific locations were considered, the negative predictive value improved at the apex, but at a cost to the positive predictive value. Tumor focality on prostatectomy specimen was the only clinical feature found to be significantly and consistently related to pathologist agreement. The authors concluded that contemporary extended-pattern prostate biopsy, although able to diagnose cancers, fails to reliably localize tumors to specific areas of the prostate. Focal therapy should be performed only with this caveat in mind.
Schulte RT, Wood DP, Daignault S, et al. Utility of extended pattern prostate biopsies for tumor localization: pathologic correlations after radical prostatectomy. Cancer. 2008;113:1559–1565.
Correspondence: Dr. John T. Wei at firstname.lastname@example.org
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The distinction between cribriform Gleason pattern three and four prostate cancer is controversial. Out of 3,590 prostate cancers sent to one of the authors during a seven-month period, 30 needle biopsy cases were selected that possibly represented cribriform Gleason pattern three cancer. Thirty-six digital images were taken and sent to 10 experts in prostate pathology. Consensus was defined when at least seven of 10 experts agreed on the grade. Sixty-seven percent (n=24) of images reached consensus (23 pattern four; one pattern three). Of the 12 nonconsensus images, seven were favor pattern four (six of 10 experts agreed), one was favor pattern three (six of 10 experts agreed), and four were equivocal (fewer than six experts agreed). The most common criteria used to identify pattern four in the 23 consensus pattern four images were, in frequency: irregular contour, irregular distribution of lumens, slit-like lumens, large glands, number of glands, and small lumens. In the only consensus pattern three image, criteria used were regular contour, small glands, regular distribution of lumens, and uniform round lumens. Discrepancy between experts was qualified as primarily objective (different criteria present) in 38 percent, subjective (different interpretation of the same criteria) in 12 percent, and mixed (objective and subjective) in 50 percent. The most frequent situation involving different interpretations of the same criteria were regular versus irregular contour and small versus large glands, with the former more common. Even in this highly selected set of images thought to be the best candidates for cribriform pattern three from a busy consult service, most experts interpreted the cribriform patterns as pattern four. Moreover, most of the cribriform foci investigated (73 percent) were associated with more definitive pattern four elsewhere on the needle biopsy specimen. The authors concluded that most of the small cribriform cancer foci seen on needle biopsy should be interpreted as Gleason pattern four and not pattern three.
Latour M, Amin MB, Billis A, et al. Grading of invasive cribriform carcinoma on prostate needle biopsy: an interobserver study among experts in genitourinary pathology. Am J Surg Pathol. 2008;32:1532–1539.
Correspondence: Dr. Jonathan I. Epstein at email@example.com
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Histopathologic diagnosis of endometrial biopsies is used to estimate risk of progression to carcinoma and guide clinical management. Problems with the widely used World Health Organization system for classifying endometrial hyperplasia (EH) have prompted the development of an alternative system based on endothelial intraepithelial neoplasia (EIN). The authors estimated progression risk associated with EIN among endometrial biopsies in a nested case-control study of EH progression. Index biopsies with original community pathology diagnoses of disordered proliferative endometrium (DPEM) or EH that were independently confirmed by a panel of pathologists were independently reviewed and assigned EIN classifications (inadequate, benign, EIN, or cancer) by a second panel of pathologists. Cases (n=138) progressed to carcinoma at least one year (median, six years) after their index biopsy. Controls (n=241) also had EH, did not progress to carcinoma, and were individually matched to cases based on age at EH, date of EH, and length of followup. Using conditional logistic regression, the authors estimated relative risks with 95 percent confidence intervals (CIs) for progression to carcinoma for EIN versus benign. In the EIN system, 71 (52.6 percent) cases and 159 (66.8 percent) controls were classified as benign and 42 (31.1 percent) cases and 65 (27.3 percent) controls were classified as EIN. The relative risk for EIN versus benign was 7.76 (95 percent CI, 3.36–17.91). Using the World Health Organization system, the relative risk for atypical hyperplasia versus DPEM, simple hyperplasia, or complex hyperplasia was 9.19 (95 percent CI, 3.87–21.83). The authors concluded that, among women observed for at least one year after receiving a biopsy-based EH diagnosis, EIN and atypical hyperplasia were found to have similarly increased risks of progression to carcinoma.
Lacey JV Jr., Mutter GL, Nucci MR, et al. Risk of subsequent endometrial carcinoma associated with endometrial intraepithelial neoplasia classification of endometrial biopsies. Cancer. 2008;113:2073–2081.
Correspondence: Dr. James V. Lacey Jr. at firstname.lastname@example.org
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Distinguishing follicular variant of papillary carcinoma from follicular adenoma and follicular carcinoma can be difficult if nuclear features of papillary carcinoma are not well developed or only focally present. The authors assessed interobserver and intraobserver agreement among six thyroid experts using 15 cases in which the original pathologists suspected follicular variant of papillary carcinoma (FVPC). There was unanimous expert agreement in diagnosing FVPC in only two cases (13 percent) and majority agreement in six cases (40 percent). Unanimous agreement about benign and malignant diagnoses occurred in four cases (27 percent) and majority agreement about malignancy in eight cases (53 percent). Intraobserver agreement ranged from 17 percent to 100 percent. Histologic features considered most helpful in diagnosing FVPC were nuclear clearing, nuclear grooves, nuclear overlapping and crowding, nuclear membrane irregularity, and nuclear enlargement. The authors concluded that this considerable interobserver and intraobserver variability in the diagnosis of FVPC seems to result from lack of agreement, even among experts, about the minimum criteria needed to diagnose FVPC.
Elsheikh TM, Asa SL, Chan JK, et al. Interobserver and intraobserver variation among experts in the diagnosis of thyroid follicular lesions with borderline nuclear features of papillary carcinoma. Am J Clin Pathol. 2008;130:736–744.
Correspondence: Dr. T. M. Elsheikh, PA Labs, Ball Memorial Hospital, 2401 University Ave., Muncie, IN 47303
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The authors conducted a study to identify the clinicopathological characteristics, treatment, and outcome of liposarcoma in an unselected, population-based patient sample and to establish whether treatment followed the Scandinavian Sarcoma Group (SSG) treatment guidelines. The SSG Pathology Board reviewed 319 liposarcoma cases reported between 1986 and 1998. After the review, 237 patients without metastases were analyzed for local recurrence rate in relation to surgical margins, radiotherapy, occurrence of metastasis, and survival. Seventy-eight percent of the patients were operated on at a sarcoma center and 45 percent had wide margins. All patients that had surgery outside the center had non-wide margins. Low-grade lesions constituted 67 percent of cases. Despite non-wide surgery, only 58 percent of high-grade lesions were treated with postoperative radiotherapy. The risk of local recurrence after non-wide surgery without irradiation was 47 percent for high-grade lesions. The estimated 10-year, local, recurrence-free and metastasis-free survival rate for the low-grade group was 87 percent and 95 percent, respectively, and for the high-grade group was 75 percent and 61 percent, respectively. Independent adverse prognostic factors for local recurrence were surgery outside a sarcoma center and histological type dedifferentiated liposarcoma. Independent adverse prognostic factors for metastases were old age, large tumor size, high grade, and histological type myxoid liposarcoma with a round cell component. Radiotherapy had a significant effect on local recurrence rate for the same grade and margin. The authors concluded that patients with liposarcoma should be treated at specialized centers. Postoperative radiotherapy decreases the local recurrence rate. Reporting to quality registers is crucial for maintaining quality and to provide support for additional trials.
Engström K, Bergh P, Gustafson P, et al. Liposarcoma: outcome based on the Scandinavian Sarcoma Group register. Cancer. 2008;113:1649–1656.
Correspondence: Dr. Katarina Engström at email@example.com
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Anatomic pathology abstracts editors: Michael Cibull, MD, professor and vice chair, Department of Pathology and Laboratory Medicine, University of Kentucky College of Medicine, Lexington; Melissa Kesler, MD, and Rouzan Karabakhtsian, MD, assistant professors of pathology and laboratory medicine, University of Kentucky College of Medicine; and Megan Zhang, MD, visiting fellow, Division of Dermatopathology, University of California, San Francisco.