Bio

Clinical Focus


  • Anatomic/Clinical Pathology

Academic Appointments


  • Associate Professor - Med Center Line, Pathology

Administrative Appointments


  • Associate Residency Director, Anatomic Pathology (2013 - Present)

Professional Education


  • Residency:University of Washington Medical Center (2006) WA
  • Fellowship:University of Washington Medical Center (2005) WA
  • Board Certification: Anatomic/Clinical Pathology, American Board of Pathology (2006)
  • Medical Education:New York Medical College (2001) NY
  • Board Certification, Amercian Board of Pathology, Anatomic and Clinical Pathology (2006)
  • Fellowship, University of Washington Medical Center, Surgical Pathology with focus of Breast/GYN Pathology (2005)
  • Residency, University of Washington Medical Center, Anatomic and Clinical Pathology (2006)
  • MD, New York Medical College (2001)
  • BA, Princeton University, Molecular Biology (1997)

Research & Scholarship

Current Research and Scholarly Interests


Dr. Allison’s clinical expertise is in breast pathology. Her research interests include how standards should be applied to breast cancer diagnostics (such as HER2 testing), the utility of molecular panel-based testing in breast cancer, and identifying the most appropriate management of specific pathologic diagnoses. She is also the author of “Red Sunshine”, a memoir about her personal experience with breast cancer, a topic which she speaks about to both patient and health care audiences.

Publications

Journal Articles


  • Development of a diagnostic test set to assess agreement in breast pathology: practical application of the Guidelines for Reporting Reliability and Agreement Studies (GRRAS) BMC WOMENS HEALTH Oster, N. V., Carney, P. A., Allison, K. H., Weaver, D. L., Reisch, L. M., Longton, G., Onega, T., Pepe, M., Geller, B. M., Nelson, H. D., Ross, T. R., Tosteson, A. N., Elmore, J. G. 2013; 13

    Abstract

    Diagnostic test sets are a valuable research tool that contributes importantly to the validity and reliability of studies that assess agreement in breast pathology. In order to fully understand the strengths and weaknesses of any agreement and reliability study, however, the methods should be fully reported. In this paper we provide a step-by-step description of the methods used to create four complex test sets for a study of diagnostic agreement among pathologists interpreting breast biopsy specimens. We use the newly developed Guidelines for Reporting Reliability and Agreement Studies (GRRAS) as a basis to report these methods.Breast tissue biopsies were selected from the National Cancer Institute-funded Breast Cancer Surveillance Consortium sites. We used a random sampling stratified according to woman's age (40-49 vs. ?50), parenchymal breast density (low vs. high) and interpretation of the original pathologist. A 3-member panel of expert breast pathologists first independently interpreted each case using five primary diagnostic categories (non-proliferative changes, proliferative changes without atypia, atypical ductal hyperplasia, ductal carcinoma in situ, and invasive carcinoma). When the experts did not unanimously agree on a case diagnosis a modified Delphi method was used to determine the reference standard consensus diagnosis. The final test cases were stratified and randomly assigned into one of four unique test sets.We found GRRAS recommendations to be very useful in reporting diagnostic test set development and recommend inclusion of two additional criteria: 1) characterizing the study population and 2) describing the methods for reference diagnosis, when applicable.

    View details for DOI 10.1186/1472-6874-13-3

    View details for Web of Science ID 000316730400001

    View details for PubMedID 23379630

  • Nonmalignant Breast Lesions: ADCs of Benign and High-Risk Subtypes Assessed as False-Positive at Dynamic Enhanced MR Imaging RADIOLOGY Parsian, S., Rahbar, H., Allison, K. H., DeMartini, W. B., Olson, M. L., Lehman, C. D., Partridge, S. C. 2012; 265 (3): 696-706

    Abstract

    To evaluate the diffusion-weighted (DW) imaging characteristics of nonmalignant lesion subtypes assessed as false-positive findings at conventional breast magnetic resonance (MR) imaging.This HIPAA-compliant retrospective study had institutional review board approval, and the need for informed patient consent was waived. Lesions assessed as Breast Imaging Reporting and Data System category 4 or 5 at clinical dynamic contrast material-enhanced MR imaging that subsequently proved nonmalignant at biopsy were retrospectively reviewed. One hundred seventy-five nonmalignant breast lesions in 165 women were evaluated. Apparent diffusion coefficients (ADCs) from DW imaging (b = 0, 600 sec/mm(2)) were calculated for each lesion and were compared between subtypes and with an ADC threshold of 1.81 × 10(-3) mm(2)/sec (determined in a prior study to achieve 100% sensitivity).Eighty-one (46%) lesions exhibited ADCs greater than the predetermined threshold. The most prevalent lesion subtypes with mean ADCs above the threshold were fibroadenoma ([1.94 ± 0.38 {standard deviation}] × 10(-3) mm(2)/sec; n = 30), focal fibrosis ([1.84 ± 0.48] × 10(-3) mm(2)/sec; n = 19), normal tissue ([1.81 ± 0.47] × 10(-3) mm(2)/sec; n = 13), apocrine metaplasia ([2.01 ± 0.38] × 10(-3) mm(2)/sec; n = 13), usual ductal hyperplasia ([1.83 ± 0.49] × 10(-3) mm(2)/sec; n = 12), and inflammation ([1.95 ± 0.46] × 10(-3) mm(2)/sec; n = 10). Atypical ductal hyperplasia ([1.48 ± 0.36] × 10(-3) mm(2)/sec; n = 23) was the most common lesion subtype with ADC below the threshold. Lymph nodes exhibited the lowest mean ADC of all nonmalignant lesions ([1.28 ± 0.23] × 10(-3) mm(2)/sec; n = 4). High-risk lesions (atypical ductal hyperplasia and lobular neoplasia) showed significantly lower ADCs than other benign lesions (P < .0001) and were the most common lesions with ADCs below the threshold.Assessing ADC along with dynamic contrast-enhanced MR imaging features may decrease the number of avoidable false-positive findings at breast MR imaging and reduce the number of preventable biopsies. The ability of DW imaging to help differentiate high-risk lesions requiring additional work-up from other nonmalignant subtypes may further improve patient care. Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12112672/-/DC1.

    View details for DOI 10.1148/radiol.12112672

    View details for Web of Science ID 000311420300006

    View details for PubMedID 23033500

  • Molecular Pathology of Breast Cancer What a Pathologist Needs to Know AMERICAN JOURNAL OF CLINICAL PATHOLOGY Allison, K. H. 2012; 138 (6): 770-780

    Abstract

    Pathologists are now more than ever "diagnostic oncologists" and serve a critical role as clinical consultants on the biology of disease. In the last decade and a half, molecular information has transformed our thinking about the biologic diversity of breast cancers and redirected the way clinical treatment decisions are made. A basic understanding of the current molecular classification of breast cancers and the biologic pathways from precursors to invasive disease is key to both informing diagnostic practice and serving as clinical consultants. In addition, both single-marker and panel-based molecular tests are currently being utilized in breast cancer tissue to predict the benefit of specific therapies such as HER2-targeted biologic therapy and chemotherapy. Familiarity with the current issues involving these molecular tests as well as the pathologist's role in ensuring appropriate tissue handling, tissue selection, and results interpretation and correlation are paramount to providing optimal patient care.

    View details for DOI 10.1309/AJCPIV9IQ1MRQMOO

    View details for Web of Science ID 000311522400002

    View details for PubMedID 23161709

  • A protein complex of SCRIB, NOS1AP and VANGL1 regulates cell polarity and migration, and is associated with breast cancer progression ONCOGENE Anastas, J. N., Biechele, T. L., Robitaille, M., Muster, J., Allison, K. H., Angers, S., Moon, R. T. 2012; 31 (32): 3696-3708

    Abstract

    By analyzing public data sets of gene expression in human breast cancers we observed that increased levels of transcripts encoding the planar cell polarity (PCP) proteins SCRIB and VANGL1 correlate with increased risk of patient relapse. Experimentally, we found that reducing expression of SCRIB by short-hairpin RNAs (shRNAs) reduces the growth of human breast cancer cells in xenograft assays. To investigate SCRIB-associated proteins that might participate in the responses of breast cancer cells to altered levels of SCRIB, we used mass spectrometry and confocal microscopy. These studies reveal that SCRIB is present in at least two unique protein complexes: (1) a complex of SCRIB, ARHGEF, GIT and PAK (p21-activated kinase), and (2) a complex of SCRIB, NOS1AP and VANGL. Focusing on NOS1AP, we observed that NOS1AP colocalizes with both SCRIB and VANGL1 along cellular protrusions in metastatic breast cancer cells, but does not colocalize with either SCRIB or VANGL1 at cell junctions in normal breast cells. We investigated the effects of shRNA-mediated knockdown of NOS1AP and SCRIB in vitro, and found that reducing NOS1AP and SCRIB slows breast cancer cell migration and prevents the establishment of leading-trailing polarity. We also find that reduction of NOS1AP enhances anchorage-independent growth. Collectively these data point to the relevance of NOS1AP and SCRIB protein complexes in breast cancer.

    View details for DOI 10.1038/onc.2011.528

    View details for Web of Science ID 000307653800004

    View details for PubMedID 22179838

  • Biomarkers of progestin therapy resistance and endometrial hyperplasia progression AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Upson, K., Allison, K. H., Reed, S. D., Jordan, C. D., Newton, K. M., Swisher, E. M., Doherty, J. A., Garcia, R. L. 2012; 207 (1)

    Abstract

    We sought to identify biomarkers associated with progestin therapy resistance and persistence/progression of endometrial hyperplasia.We performed a nested case-control study among women with complex (n = 73) and atypical (n = 41) hyperplasia treated with oral progestin, followed up 2-6 months for persistence/progression. We evaluated index endometrial protein expression for progesterone receptor isoform A, progesterone receptor isoform B (PRB), PTEN, Pax-2, and Bcl-2. Odds ratios and 95% confidence intervals (CIs) were estimated.Among women with atypical hyperplasia, high PRB expression was associated with 90% decreased risk of persistence/progression (95% CI, 0.01-0.8). High expression of progesterone receptor A and PRB suggested decreased risk of persistence/progression (odds ratio, 0.1; 95% CI, 0.02-1.0). These findings were not observed among women with complex hyperplasia. No associations were found with PTEN, Pax-2, and Bcl-2 protein expression.PRB expression shows promise as a biomarker of progestin response. Further research is warranted to understand how PRB expression may guide treatment decisions.

    View details for DOI 10.1016/j.ajog.2012.05.012

    View details for Web of Science ID 000305755000013

    View details for PubMedID 22727345

  • In Vivo Assessment of Ductal Carcinoma in Situ Grade: A Model Incorporating Dynamic Contrast-enhanced and Diffusion-weighted Breast MR Imaging Parameters RADIOLOGY Rahbar, H., Partridge, S. C., DeMartini, W. B., Gutierrez, R. L., Allison, K. H., Peacock, S., Lehman, C. D. 2012; 263 (2): 374-382

    Abstract

    To develop a model incorporating dynamic contrast material-enhanced (DCE) and diffusion-weighted (DW) magnetic resonance (MR) imaging features to differentiate high-nuclear-grade (HNG) from non-HNG ductal carcinoma in situ (DCIS) in vivo.This HIPAA-compliant study was approved by the institutional review board and requirement for informed consent was waived. A total of 55 pure DCIS lesions (19 HNG, 36 non-HNG) in 52 women who underwent breast MR imaging at 1.5 T with both DCE and DW imaging (b = 0 and 600 sec/mm(2)) were retrospectively reviewed. The following lesion characteristics were recorded or measured: DCE morphology, DCE maximum lesion size, peak initial enhancement at 90 seconds, worst-curve delayed enhancement kinetics, apparent diffusion coefficient (ADC), contrast-to-noise ratio (CNR) at DW imaging with b values of 0 and 600 sec/mm(2), and T2 signal effects (measured with CNR at b = 0 sec/mm(2)). Univariate and stepwise multivariate logistic regression modeling was performed to identify MR imaging features that optimally discriminated HNG from non-HNG DCIS. Discriminative abilities of models were compared by using the area under the receiver operating characteristic curve (AUC).HNG lesions exhibited larger mean maximum lesion size (P = .02) and lower mean CNR for images with b value of 600 sec/mm(2) (P = .004), allowing discrimination of HNG from non-HNG DCIS (AUC = 0.71 for maximum lesion size, AUC = 0.70 for CNR at b = 600 sec/mm(2)). Differences in CNR for images with b value of 0 sec/mm(2) (P = .025) without corresponding differences in ADC values were observed between HNG and non-HNG lesions. Peak initial enhancement was the only kinetic variable to approach significance (P = .05). No differences in lesion morphology (P = .11) or worst-curve delayed enhancement kinetics (P = .97) were observed. A multivariate model combining CNR for images with b value of 600 sec/mm(2) and maximum lesion size most significantly discriminated HNG from non-HNG (AUC = 0.81).The preliminary findings suggest that DCE and DW MR imaging features may aid in identifying patients with high-risk DCIS. Further study may yield a model combining MR characteristics with histopathologic data to facilitate lesion-specific targeted therapies. © RSNA, 2012.

    View details for DOI 10.1148/radiol.12111368

    View details for Web of Science ID 000303104300007

    View details for PubMedID 22517955

  • Lobular In-Situ Neoplasia on Breast Core Needle Biopsy: Imaging Indication and Pathologic Extent Can Identify Which Patients Require Excisional Biopsy ANNALS OF SURGICAL ONCOLOGY Rendi, M. H., Dintzis, S. M., Lehman, C. D., Calhoun, K. E., Allison, K. H. 2012; 19 (3): 914-921

    Abstract

    The surgical management of lobular in-situ neoplasia (LN) identified by core needle biopsy (CNB) is currently variable. Our institution has routinely excised LN on CNB since 2003, allowing for an unbiased assessment of upgrade rates.Cases of LN on CNB, including atypical lobular hyperplasia (ALH) and lobular carcinoma-in-situ (LCIS), were identified in our pathology database. CNBs with concurrent pleomorphic LCIS, ductal carcinoma-in-situ (DCIS), and invasive carcinoma were excluded. Imaging indication/modality, biopsy indication, and radiologic concordance were determined. Pathology review included scoring total foci of LN in each CNB. Upgrade rates to invasive carcinoma or DCIS at excision were calculated.A total of 106 cases of LN (73 ALH and 33 LCIS) on CNB were identified. Thirty patients had concurrent atypical ductal hyperplasia (ADH) and 76 had LN alone; 93 (88%) of the patients had available surgical follow-up (25 LN + ADH and 68 LN alone). The upgrade rate at excision was 16% (4 of 25) for LN + ADH and 4.4% (3 of 68) for LN alone. Patients with LN alone and discordant imaging, imaging for high-risk indications, or extensive LCIS (>4 foci) accounted for all the upgrades. Normal-risk patients who underwent biopsy to assess calcifications found by routine mammographic screening with LN alone did not result in upgrade.Women with a CNB diagnosis of LN for calcifications found on routine, normal-risk mammographic screening have a negligible risk of upgrade and may not require excisional biopsy. However, excisional biopsy should be offered to women undergoing imaging for other indications or with >4 foci of LN on CNB.

    View details for DOI 10.1245/s10434-011-2034-3

    View details for Web of Science ID 000300313800031

    View details for PubMedID 21861212

  • PAX2 Loss by Immunohistochemistry Occurs Early and Often in Endometrial Hyperplasia INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY Allison, K. H., Upson, K., Reed, S. D., Jordan, C. D., Newton, K. M., Doherty, J., Swisher, E. M., Garcia, R. L. 2012; 31 (2): 159-167
  • PAX2 loss by immunohistochemistry occurs early and often in endometrial hyperplasia. International journal of gynecological pathology Allison, K. H., Upson, K., Reed, S. D., Jordan, C. D., Newton, K. M., Doherty, J., Swisher, E. M., Garcia, R. L. 2012; 31 (2): 151-159

    Abstract

    Immunohistochemical markers to assist in the diagnosis and classification of hyperplastic endometrial epithelial proliferations would be of diagnostic use. To examine the possible use of PAX2 as a marker of hyperplastic endometrium, cases of normal endometrium, simple and complex hyperplasia without atypia, atypical hyperplasia, and International Federation of Gynecology and Obstetrics (FIGO) grade 1 endometrioid carcinomas were stained for PAX2. Two hundred and six endometrial samples were available for interpretation of PAX2 staining. The percentage of cases with complete PAX2 loss (0% of cells staining) increased with increasing severity of hyperplasia: 0% of normal proliferative and secretory endometrium (n=28), 17.4% of simple hyperplasia (n=23), 59.0% of complex hyperplasia (n=83), 74.1% of atypical hyperplasia (n=54), and 73.3% of FIGO grade 1 endometrioid cancers (n=15). Partial loss of PAX2 expression did occur in normal endometrium (17.9%) but in smaller proportions of tissue and was less frequent than in simple hyperplasia (47.8% with partial loss), complex hyperplasia (32.5%), atypical hyperplasia (22.2%), and FIGO grade 1 carcinomas (20.0%). Uniform PAX2 expression was rare in complex (8.4%) and atypical hyperplasia (3.7%) and carcinoma (6.7%). When evaluating loss of PAX2 in histologically normal endometrium adjacent to lesional endometrium in a given case, statistically significant differences in staining were observed for simple hyperplasia (P=0.011), complex hyperplasia (P<0.001), atypical hyperplasia (P<0.001), and FIGO grade 1 endometrioid cancer (P=0.003). In summary, PAX2 loss seems to occur early in the development of endometrial precancers and may prove useful in some settings as a diagnostic marker in determining normal endometrium from complex and atypical hyperplasia and low-grade carcinomas. However, it is not useful in distinguishing between these diagnostic categories.

    View details for DOI 10.1097/PGP.0b013e318226b376

    View details for PubMedID 22317873

  • Routine pathologic parameters can predict Oncotype DXTM recurrence scores in subsets of ER positive patients: who does not always need testing? BREAST CANCER RESEARCH AND TREATMENT Allison, K. H., Kandalaft, P. L., Sitlani, C. M., Dintzis, S. M., GOWN, A. M. 2012; 131 (2): 413-424

    Abstract

    Oncotype DX(TM) is an RT-PCR-based assay used to predict chemotherapy benefit in patients with estrogen receptor (ER) positive breast cancers. We were interested if routinely available pathologic parameters could predict Oncotype DX Recurrence Scores (RS) in subsets of patients. We identified 173 breast cancers with available RSs and used 104 of these as a test set and 69 cases as a validation set. Pathologic characteristics including size, histologic type, Nottingham grade, and lymphatic invasion were recorded. Test set cases were stained for ER, progesterone receptor (PR), HER2, Ki67, CyclinD1, BCL2, D2-40, and P53. Statistical correlations with RS and regression tree analysis were performed. The validation set was subjected to analysis on the basis of grade, PR, and Ki67. In the test set, grade, PR levels and Ki67 had the strongest correlation with RS (P = 0.0002-0.0007). Regression tree analysis showed grade and PR as factors that could segregate cases into RS categories, with Ki67 adding value in certain subsets. A subset of cancers with a high likelihood of having a low RS (0-18) was identified with the following characteristics: grade 1, strong PR expression (Allred score ? 5) and Ki67 ? 10%. No cases with these characteristics had a high RS (? 31) and 73% had a low RS. Cancers highly likely to have a high RS were grade 3, low to absent PR expression (Allred score <5) and Ki67 > 10%. 80% of cases with these characteristics had a high RS and no cases had a low RS. Our validation set had similar findings in these two subsets. In conclusion, When cost and time are a consideration and the added value of Oncotype DX(TM) testing is in question, it may be reasonable to assume the results of this test in two specific subsets of breast cancers: (1) grade 1, high PR, low Ki67 cancers (low RS), and (2) grade 3, low PR, high Ki67 cancers (high RS).

    View details for DOI 10.1007/s10549-011-1416-3

    View details for Web of Science ID 000298752200005

    View details for PubMedID 21369717

  • Mouse cursor movement and eye tracking data as an indicator of pathologists' attention when viewing digital whole slide images. Journal of pathology informatics Raghunath, V., Braxton, M. O., Gagnon, S. A., Brunyé, T. T., Allison, K. H., Reisch, L. M., Weaver, D. L., Elmore, J. G., Shapiro, L. G. 2012; 3: 43-?

    Abstract

    Digital pathology has the potential to dramatically alter the way pathologists work, yet little is known about pathologists' viewing behavior while interpreting digital whole slide images. While tracking pathologist eye movements when viewing digital slides may be the most direct method of capturing pathologists' viewing strategies, this technique is cumbersome and technically challenging to use in remote settings. Tracking pathologist mouse cursor movements may serve as a practical method of studying digital slide interpretation, and mouse cursor data may illuminate pathologists' viewing strategies and time expenditures in their interpretive workflow.To evaluate the utility of mouse cursor movement data, in addition to eye-tracking data, in studying pathologists' attention and viewing behavior.Pathologists (N = 7) viewed 10 digital whole slide images of breast tissue that were selected using a random stratified sampling technique to include a range of breast pathology diagnoses (benign/atypia, carcinoma in situ, and invasive breast cancer). A panel of three expert breast pathologists established a consensus diagnosis for each case using a modified Delphi approach.Participants' foveal vision was tracked using SensoMotoric Instruments RED 60 Hz eye-tracking system. Mouse cursor movement was tracked using a custom MATLAB script.Data on eye-gaze and mouse cursor position were gathered at fixed intervals and analyzed using distance comparisons and regression analyses by slide diagnosis and pathologist expertise. Pathologists' accuracy (defined as percent agreement with the expert consensus diagnoses) and efficiency (accuracy and speed) were also analyzed.Mean viewing time per slide was 75.2 seconds (SD = 38.42). Accuracy (percent agreement with expert consensus) by diagnosis type was: 83% (benign/atypia); 48% (carcinoma in situ); and 93% (invasive). Spatial coupling was close between eye-gaze and mouse cursor positions (highest frequency ?x was 4.00px (SD = 16.10), and ?y was 37.50px (SD = 28.08)). Mouse cursor position moderately predicted eye gaze patterns (Rx = 0.33 and Ry = 0.21).Data detailing mouse cursor movements may be a useful addition to future studies of pathologists' accuracy and efficiency when using digital pathology.

    View details for DOI 10.4103/2153-3539.104905

    View details for PubMedID 23372984

  • Feasibility study of FDG PET as an indicator of early response to aromatase inhibitors and trastuzumab in a heterogeneous group of breast cancer patients. EJNMMI research Kurland, B. F., Gadi, V. K., Specht, J. M., Allison, K. H., Livingston, R. B., Rodler, E. T., Peterson, L. M., Schubert, E. K., Chai, X., Mankoff, D. A., Linden, H. M. 2012; 2 (1): 34-?

    Abstract

    In breast cancer endocrine therapy, post-therapy Ki-67 assay of biopsy material predicts recurrence-free survival but is invasive and prone to sampling error. [18F]Fluorodeoxyglucose (FDG) positron emission tomography (PET) has shown an early agonist or 'flare' response to tamoxifen and estradiol, but has not been tested in response to estrogen-lowering aromatase inhibitors (AIs). We hypothesized that decreased agonistic response to AIs would result in early FDG uptake decline. We also measured early response to trastuzumab (T), another targeted agent for breast cancer with differing mechanisms of action. Our study was designed to test for an early decline in FDG uptake in response to AI or T and to examine association with Ki-67 measures of early response.Patients with any stage of newly diagnosed or recurrent breast cancer were eligible and enrolled prior to initiation (or resumption) of AI or T therapy. FDG PET and tissue biopsy were planned before and after 2 weeks of AI or T therapy, with pretreatment archival tissue permitted. Cutoffs of ?20% decline in standardized uptake value (SUV) as FDG PET early response and ?5% post-treatment expression as Ki-67 early response were defined prior to analysis.Forty-two patients enrolled, and 40 (28 AI, 12 T) completed serial FDG-PET imaging. Twenty-two patients (17 AI, 5 T) had newly diagnosed disease, and 23 (14 AI, 9 T) had metastatic disease (5 newly diagnosed). Post-treatment biopsy was performed in 25 patients (63%) and was either refused or not feasible in 15. Post-treatment biopsy yielded tumor in only 17/25 cases (14 AI, 3 T). Eleven of 14 AI patients with post-therapy tissue showed FDG PET early response, and there was 100% concordance of PET and post-therapy Ki-67 early response. For the T group, 6/12 showed an FDG PET early response, including 2/3 patients with post-therapy biopsy, all with Ki-67 >5%.Substantial changes in FDG PET SUV occurred over 2 weeks of AI therapy and were associated with low post-therapy proliferation. SUV decline was seen in response to T, but few tissue samples were available to test association with Ki-67. Our results support further investigation of FDG PET as a biomarker for early response to AI therapy.

    View details for DOI 10.1186/2191-219X-2-34

    View details for PubMedID 22731662

  • Frequency of HER2 Heterogeneity by Fluorescence In Situ Hybridization According to CAP Expert Panel Recommendations Time for a New Look at How to Report Heterogeneity AMERICAN JOURNAL OF CLINICAL PATHOLOGY Allison, K. H., Dintzis, S. M., Schmidt, R. A. 2011; 136 (6): 864-871

    Abstract

    In 2009, a College of American Pathologists expert panel published supplemental HER2 testing recommendations suggesting that cases with between 5% and 50% individual cells amplified by fluorescence in situ hybridization be reported as "heterogeneous for HER2 gene amplification." We examined the implications of applying these recommendations to clinical practice in 1,329 consecutive breast cancer cases. By ratio criteria, 23.2% of cases met the proposed criteria for heterogeneity, of which 81.6% were not amplified and 15.5% were equivocal by standard criteria. In contrast, the proposed criteria based on HER2 signals per cell classified only 6.5% of cases as heterogeneous, of which only 8% (7/87) were not amplified and 79% (69/87) were equivocal by standard criteria. These results show that the 2 proposed criteria sets are not equivalent and that the ratio-based definition results in large numbers of nonamplified cases being classified as heterogeneous. Further definition of optimal criteria with clinical relevance is needed before HER2 heterogeneity reporting is adopted in routine practice.

    View details for DOI 10.1309/AJCPXTZSKBRIP07W

    View details for Web of Science ID 000297274500006

    View details for PubMedID 22095371

  • FOXP3+regulatory T-cells are abundant in vulvar Paget's disease and are associated with recurrence GYNECOLOGIC ONCOLOGY Press, J. Z., Allison, K. H., Garcia, R., Everett, E. N., Pizer, E., Swensen, R. E., Tamimi, H. K., Gray, H. J., Peters, W. A., Goff, B. A. 2011; 120 (2): 296-299

    Abstract

    To characterize clinical features of vulvar Paget's disease, and examine the quantity of immunosuppressive regulatory T-cells in vulvar Paget's tissue.Vulvar Paget's cases from 1992 to 2007 from two institutions were identified by pathology database search. Regulatory T-cells were identified with FOXP3 immunohistochemistry and quantified at the dermal-epidermal junction using image analysis software. Thirteen non-neoplastic inflammatory cases were stained for comparison.Cases included 33 women treated for primary vulvar Paget's, and 7 referred at recurrence. Of the 24 primary cases with greater than 5 months follow-up, recurrence was documented in 12/24(50%). Eight women (20%) recurred multiple times, but no recurrences were invasive. Significantly more patients with positive margins developed recurrent disease (82% vs 23%, p=0.01). Secondary neoplasms occurred in 10/40(25%). FOXP3+ cells at the dermal-epidermal junction were quantified in 29 primary and 13 recurrent tissue samples. FOXP3+ cells were absent in surrounding normal vulvar skin. FOXP3+ cells averaged 66/HPF in primary vulvar Paget's and 66/HPF in recurrent Paget's, compared to 22/HPF in non-neoplastic inflammatory cases (p=0.0003, p=0.001). Primary cases with positive surgical margins had more FOXP3+ cells than those with negative margins (85 vs 49, p=0.01). Recurrent cases with positive margins had more FOXP3+ cells than negative cases (84 vs 33, p=0.06). FOXP3 levels in primary specimens were higher in cases which recurred (78 vs 35, p=0.02).Increased regulatory T-cells may be associated with more extensive cases of vulvar Paget's disease that result in positive surgical margins and are associated with recurrence of disease, suggesting immunosuppression as a key factor.

    View details for DOI 10.1016/j.ygyno.2010.10.019

    View details for Web of Science ID 000286856800025

    View details for PubMedID 21075432

  • Endogenous Versus Tumor-Specific Host Response to Breast Carcinoma: A Study of Stromal Response in Synchronous Breast Primaries and Biopsy Site Changes CLINICAL CANCER RESEARCH Wu, J. M., Beck, A. H., Pate, L. L., Witten, D., Zhu, S. X., Montgomery, K. D., Allison, K. H., van de Rijn, M., West, R. B. 2011; 17 (3): 437-446

    Abstract

    We recently described two types of stromal response in breast cancer derived from gene expression studies of tenosynovial giant cell tumors and fibromatosis. The purpose of this study is to elucidate the basis of this stromal response--whether they are elicited by individual tumors or whether they represent an endogenous host reaction produced by the patient.Stromal signatures from patients with synchronous dual primaries were analyzed by immunohistochemistry on a tissue microarray (n = 26 pairs) to evaluate the similarity of stromal responses in different tumors within the same patient. We also characterized the extent to which the stromal signatures were conserved between stromal response to injury compared to the stromal response to carcinoma using gene expression profiling and tissue microarray immunohistochemistry.The two stromal response signatures showed divergent associations in synchronous primaries: the DTF fibroblast response is more likely to be similar in a patient with multiple breast primaries (permutation analysis P = 0.0027), whereas CSF1 macrophage response shows no significant concordance in separate tumors within a given patient. The DTF fibroblast signature showed more concordance across normal, cancer, and biopsy site samples from within a patient, than across normal, cancer, and biopsy site samples from a random group of patients, whereas the CSF1 macrophage response did not.The results suggest that the DTF fibroblast response is host-specific, whereas the CSF1 response may be tumor-elicited. Our findings provide further insight into stromal response and may facilitate the development of therapeutic strategies to target particular stromal subtypes.

    View details for DOI 10.1158/1078-0432.CCR-10-1709

    View details for Web of Science ID 000286873400007

    View details for PubMedID 21098336

  • Atypical ductal hyperplasia on vacuum-assisted breast biopsy: suspicion for ductal carcinoma in situ can stratify patients at high risk for upgrade HUMAN PATHOLOGY Allison, K. H., Eby, P. R., Kohr, J., DeMartini, W. B., Lehman, C. D. 2011; 42 (1): 41-50

    Abstract

    We evaluated 97 cases of review-confirmed atypical ductal hyperplasia found on stereotactic vacuum-assisted breast biopsy of suspicious calcifications. The number and size of foci of atypical ductal hyperplasia and presence of a micropapillary component were noted. In addition, we recorded if a case was considered "atypical ductal hyperplasia suspicious for ductal carcinoma in situ" using specific qualitative criteria. The upgrade rate was 20.6% (20/97) for all cases and 48% (12/25) for cases suspicious for ductal carcinoma in situ. Suspicion for ductal carcinoma in situ was found to be a strong predictor of upgrade with an odds ratio of 7.4 (P = .0003). Suspicious cases with nuclear features bordering on intermediate nuclear grade had the highest upgrade rate of 75% (6/8). Cases with ? 3 foci had significantly higher upgrade rates (28%) than those with less than 3 foci (11%), but focal atypical ductal hyperplasia did upgrade (P = .04). In conclusion, qualitative features of atypical ductal hyperplasia on core biopsy such as suspicion for ductal carcinoma in situ may help stratify patients at the highest risk for upgrade.

    View details for DOI 10.1016/j.humpath.2010.06.011

    View details for Web of Science ID 000285527600006

    View details for PubMedID 20970167

  • The Molecular Pathogenesis of Hereditary Ovarian Carcinoma CANCER Norquist, B. M., Garcia, R. L., Allison, K. H., Jokinen, C. H., Kernochan, L. E., Pizzi, C. C., Barrow, B. J., Goff, B. A., Swisher, E. M. 2010; 116 (22): 5261-5271

    Abstract

    BRCA1 or BRCA2 (BRCA1/2)-mutated ovarian carcinomas may originate in the fallopian tube. The authors of this report investigated alterations in BRCA1/2 tubal epithelium to define the molecular pathogenesis of these carcinomas.Tubal epithelium was evaluated from 31 BRCA1/2 mutation carriers with gynecologic carcinomas (BRCA CA), 89 mutation carriers who underwent risk-reducing salpingo-oophorectomy (RRSO), and 87 controls. Ki-67 expression and p53 foci (?10 of 12 consecutive staining cells) were scored by 2 investigators who were blinded to patient designations. Expression levels of p27 and p21 were evaluated within p53 foci. Loss of heterozygosity at the BRCA1/2 mutation site was evaluated in microdissected p53 foci and tubal neoplasms.Background tubal proliferation as measured by Ki-67 staining was increased in the BRCA1 RRSO group (P = .005) compared with the control group. Women who had BRCA1/2 mutations had more p53 foci identified per tubal segment than women in the control group (P = .02). Levels of p27 were decreased in 12 of 28 p53 foci from women with BRCA1 mutations and in 0 of 16 p53 foci from controls (P = .002). There was no loss of the wild type BRCA1/2 allele in 5 tested p53 foci. Tubal neoplasia lost the wild type allele in 6 of 6 foci (P = .002).The current results suggested a model of tubal carcinogenesis in women with BRCA1/2 mutations. Increased proliferation occurred globally in at-risk tubal epithelium. A mutation in the tumor protein p53 gene TP53 with clonal proliferation and loss of p27 occurred before neoplastic proliferation. Loss of the wild type BRCA1/2 allele occurred with neoplastic proliferation and before invasion.

    View details for DOI 10.1002/cncr.25439

    View details for Web of Science ID 000284047400018

    View details for PubMedID 20665887

  • Frequency, Upgrade Rates, and Characteristics of High-Risk Lesions Initially Identified With Breast MRI AMERICAN JOURNAL OF ROENTGENOLOGY Strigel, R. M., Eby, P. R., DeMartini, W. B., Gutierrez, R. L., Allison, K. H., Peacock, S., Lehman, C. D. 2010; 195 (3): 792-798

    Abstract

    The purpose of this article is to determine the frequency, outcomes, and imaging features of high-risk lesions initially detected by breast MRI, including atypical ductal hyperplasia, atypical lobular hyperplasia, lobular carcinoma in situ, and radial scar.A retrospective review of our MRI pathology database was performed to identify all lesions initially detected with MRI (January 2003 through May 2007) that underwent imaging-guided needle biopsy yielding high-risk histopathologic abnormalities. Patient age, clinical indication, MRI BI-RADS lesion features, biopsy method, and histopathologic diagnosis were recorded. The frequencies of high-risk findings at needle biopsy and rates of upgrade to malignancy at surgical excision were compared across lesion imaging features with Fisher's exact test.Four hundred eighty-two MRI-detected suspicious lesions underwent needle biopsy. High-risk histopathologic abnormalities were present in 61 (12.7%) of 482 lesions: 51 (10.6%) atypical ductal hyperplasias, six (1.2%) atypical lobular hyperplasias, three (0.6%) lobular carcinomas in situ, and one (0.2%) radial scar. Correlation between the lesion site and pathology at surgical excision was confirmed for 39 of 61 lesions. Twelve (30.8%) of those 39 lesions were upgraded to malignancy (11 atypical ductal hyperplasias and one atypical lobular hyperplasia); five (41.7%) of the 12 malignancies were invasive cancer, and seven (58.3%) were ductal carcinomas in situ. No significant lesion features predictive of subsequent upgrade to malignancy were discovered.There are no specific imaging features that predict upgrade for high-risk lesions when detected with MRI. Therefore, surgical excision is recommended because upgrade to invasive carcinoma or ductal carcinoma in situ can occur in up to 31% of cases, regardless of biopsy technique.

    View details for DOI 10.2214/AJR.09.4081

    View details for Web of Science ID 000281180500037

    View details for PubMedID 20729462

  • Complex Hyperplasia With and Without Atypia Clinical Outcomes and Implications of Progestin Therapy OBSTETRICS AND GYNECOLOGY Reed, S. D., Newton, K. M., Garcia, R. L., Allison, K. H., Voigt, L. F., Jordan, C. D., Epplein, M., Swisher, E., Upson, K., Ehrlich, K. J., Weiss, N. S. 2010; 116 (2): 365-373

    Abstract

    Limited data exist to inform clinicians and patients as to the likelihood of long-term endometrial hyperplasia response to progestin therapy, especially for atypical hyperplasia. We evaluated women with complex and atypical endometrial hyperplasia, comparing those prescribed progestin with those not prescribed progestin.This retrospective cohort study was conducted in 1985-2005 among women aged 18-88 years at an integrated health plan in Washington State. Women were ineligible if they achieved an outcome (endometrial carcinoma, hysterectomy, or both) within 8 weeks of hyperplasia diagnosis. Exposure was progestin use for at least 14 days by duration and recency. Outcomes included rate of 1) endometrial carcinoma, 2) hysterectomy, or 3) both. Analyses performed included Kaplan-Meier, incident rate ratios, and Cox proportional hazard ratios.One thousand four hundred forty-three eligible women were identified. One thousand two hundred one had complex (n=164 no progestin) and 242 had atypical (n=62 no progestin) hyperplasia. During follow-up, a median of 5.3 years (range 8 weeks to 20.8 years), 71 women were diagnosed with endometrial carcinoma (35 complex, 36 atypia) and 323 underwent hysterectomy (216 complex, 107 atypia). Among women with complex and atypical hyperplasia, rates of endometrial carcinoma among progestin users were 3.6 and 20.5 per 1,000 woman-years, respectively (compared with women who did not use progestin, 10.8 and 101.4). Among women with complex and atypical hyperplasia, rates of hysterectomy among progestin users were 23.3 and 61.4 per 1,000 woman-years, respectively (compared with women who did not use progestin, 55.1 and 297.3).Endometrial carcinoma risk is diminished approximately threefold to fivefold in women diagnosed with complex or atypical endometrial hyperplasia and dispensed progestin; hysterectomy risk is also decreased.II.

    View details for DOI 10.1097/AOG.0b013e3181e93330

    View details for Web of Science ID 000280186300017

    View details for PubMedID 20664397

  • Achieving 95% Cross-Methodological Concordance in HER2 Testing Causes and Implications of Discordant Cases AMERICAN JOURNAL OF CLINICAL PATHOLOGY Grimm, E. E., Schmidt, R. A., Swanson, P. E., Dintzis, S. M., Allison, K. H. 2010; 134 (2): 284-292

    Abstract

    We were interested in determining our concordance between fluorescence in situ hybridization (FISH) and a previously validated immunohistochemical HER2 assay to identify possible reasons for discordance and to determine if all reasons for discordance were addressed by the American Society of Clinical Oncology/College of American Pathologists guidelines. We reviewed 697 cases (2004-2007) in which HER2 immunohistochemical and FISH testing were concurrently done. Overall concordance between nonequivocal immunohistochemical and FISH results was 96%. Of the 19 discordant cases, 13 (68%) were interpreted as positive immunohistochemically but negative by FISH. The primary reason for this discordance was immunohistochemical interpretation. Weak stain intensity, granular staining, and interpretation in areas of crush artifact were identified as the most common issues. Of the 6 cases interpreted as immunohistochemically negative and FISH-positive, 2 were from patients known to be receiving trastuzumab at the time of biopsy, 1 was very close to the FISH equivocal category, and 4 cases had fewer than 1.5 CEP17 signals per cell (1 patient in this group was also receiving trastuzumab). Focusing on issues with HER2 immunohistochemical interpretation can improve concordance rates for immunohistochemically positive cases, but biologic reasons may explain some discordant immunohistochemically negative cases.

    View details for DOI 10.1309/AJCPUQB18XZOHHBJ

    View details for Web of Science ID 000280067600016

    View details for PubMedID 20660333

  • Risk of Upgrade of Atypical Ductal Hyperplasia after Stereotactic Breast Biopsy: Effects of Number of Foci and Complete Removal of Calcifications RADIOLOGY Kohr, J. R., Eby, P. R., Allison, K. H., DeMartini, W. B., Gutierrez, R. L., Peacock, S., Lehman, C. D. 2010; 255 (3): 723-730

    Abstract

    To determine if patients with fewer than three foci of atypical ductal hyperplasia (ADH) who have all of their calcifications removed after stereotactic 9- or 11-gauge vacuum-assisted breast biopsy (VABB) have a rate of upgrade to malignancy that is sufficiently low to obviate surgical excision.An institutional review board-approved, HIPAA-compliant retrospective review of 991 cases of consecutive 9- or 11-gauge stereotactic VABB performed during a 65-month period revealed 147 cases of atypia. One pathologist performed a blinded review of the results of procedures performed to assess for calcifications and confirmed ADH in 101 cases with subsequent surgical excision. Each large duct or terminal duct-lobular unit containing ADH was considered a focus and counted. Postbiopsy mammograms were reviewed to determine whether all calcifications were removed. Upgrade to malignancy was determined from excisional biopsy pathology reports. Upgrade rates as a function of both number of foci and presence or absence of residual calcifications were calculated and compared by using chi(2) tests.Upgrade to malignancy occurred in 20 (19.8%) of the 101 cases. The upgrade rate was significantly higher in cases of three or more foci of ADH (15 [28%] of 53 cases) than in cases of fewer than three foci (five [10%] of 48 cases) (P = .02). Upgrade rates were similar, regardless of whether all mammographic calcifications were removed (seven [17%] of 41 cases) or all were not removed (nine [20%] of 45 cases) (P = .77). Upgrade occurred in two (12%) of 17 cases in which there were fewer than three ADH foci and all calcifications were removed.The upgrade rate is significantly higher when ADH involves at least three foci. Surgical excision is recommended even when ADH involves fewer than three foci and all mammographic calcifications have been removed, because the upgrade rate is 12%.

    View details for DOI 10.1148/radiol.09091406

    View details for Web of Science ID 000278038500009

    View details for PubMedID 20173103

  • Tumor Metabolism and Blood Flow as Assessed by Positron Emission Tomography Varies by Tumor Subtype in Locally Advanced Breast Cancer CLINICAL CANCER RESEARCH Specht, J. M., Kurland, B. F., Montgomery, S. K., Dunnwald, L. K., Doot, R. K., Gralow, J. R., Ellis, G. K., Linden, H. M., Livingston, R. B., Allison, K. H., Schubert, E. K., Mankoff, D. A. 2010; 16 (10): 2803-2810

    Abstract

    Dynamic positron emission tomography (PET) imaging can identify patterns of breast cancer metabolism and perfusion in patients receiving neoadjuvant chemotherapy (NC) that are predictive of response. This analysis examines tumor metabolism and perfusion by tumor subtype.Tumor subtype was defined by immunohistochemistry in 71 patients with locally advanced breast cancer undergoing NC. Subtype was defined as luminal [estrogen receptor (ER)/progesterone receptor (PR) positive], triple negative [TN; ER/PR negative, human epidermal growth factor receptor 2 (HER2) negative], and HER2 (ER/PR negative, HER2 overexpressing). Metabolic rate (MRFDG) and blood flow (BF) were calculated from PET imaging before NC. Pathologic complete response (pCR) to NC was classified as pCR versus other.Twenty-five (35%) of 71 patients had TN tumors; 6 (8%) were HER2 and 40 (56%) were luminal. MRFDG for TN tumors was on average 67% greater than for luminal tumors (95% confidence interval, 9-156%) and average MRFDG/BF ratio was 53% greater in TN compared with luminal tumors (95% confidence interval, 9-114%; P<0.05 for both). Average BF levels did not differ by subtype (P=0.73). Most luminal tumors showed relatively low MRFDG and BF (and did not achieve pCR); high MRFDG was generally matched with high BF in luminal tumors and predicted pCR. This was not true in TN tumors.The relationship between breast tumor metabolism and perfusion differed by subtype. The high MRFDG/BF ratio that predicts poor response to NC was more common in TN tumors. Metabolism and perfusion measures may identify subsets of tumors susceptible and resistant to NC and may help direct targeted therapy.

    View details for DOI 10.1158/1078-0432.CCR-10-0026

    View details for Web of Science ID 000278597600012

    View details for PubMedID 20460489

  • Diffusion tensor magnetic resonance imaging of the normal breast MAGNETIC RESONANCE IMAGING Partridge, S. C., Murthy, R. S., Ziadloo, A., White, S. W., Allison, K. H., Lehman, C. D. 2010; 28 (3): 320-328

    Abstract

    The objective of this study was to evaluate diffusion anisotropy of the breast parenchyma and assess the range and repeatability of diffusion tensor imaging (DTI) parameters in normal breast tissue.The study was approved by our institutional review board and included 12 healthy females (median age, 36 years). Diffusion tensor imaging was performed at 1.5 T using a diffusion-weighted echo planar imaging sequence. Diffusion tensor imaging parameters including tensor eigenvalues (lambda(1), lambda(2), lambda(3)), fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were measured for anterior, central and posterior breast regions.Mean normal breast DTI measures were lambda(1)=2.51 x 10(-3) mm(2)/s, lambda(2)=1.89 x 10(-3) mm(2)/s, lambda(3)=1.39 x 10(-3) mm(2)/s, ADC=1.95+/-0.24 x 10(-3) mm(2)/s and FA=0.29+/-0.05 for b=600 s/mm(2). Significant regional differences were observed for both FA and ADC (P<.05), with higher ADC in the central breast and higher FA in the posterior breast. Comparison of DTI values calculated using b=0, 600 s/mm(2) vs. b=0, 1000 s/mm(2), showed significant differences in ADC (P<.001), but not FA. Repeatability assessment produced within-subject coefficient of variations of 4.5% for ADC and 11.4% for FA measures.This study demonstrates anisotropy of water diffusion in normal breast tissue and establishes a normative range of breast FA values. Attention to the influence of breast region and b value on breast DTI measurements may be important for clinical interpretation and standardization of techniques.

    View details for DOI 10.1016/j.mri.2009.10.003

    View details for Web of Science ID 000276042400003

    View details for PubMedID 20061111

  • Frequency and Upgrade Rates of Atypical Ductal Hyperplasia Diagnosed at Stereotactic Vacuum-Assisted Breast Biopsy: 9-Versus 11-Gauge AMERICAN JOURNAL OF ROENTGENOLOGY Eby, P. R., Ochsner, J. E., DeMartini, W. B., Allison, K. H., Peacock, S., Lehman, C. D. 2009; 192 (1): 229-234

    Abstract

    Our goals were to determine the frequency and upgrade rate for atypical ductal hyperplasia (ADH) diagnosed with stereotactic 9-gauge vacuum-assisted breast biopsy and to compare the frequencies and upgrade rates of ADH between 9- and 11-gauge vacuum-assisted breast biopsy.We retrospectively reviewed the pathology results of 991 consecutive 9- or 11-gauge stereotactic vacuum-assisted breast biopsy procedures from February 2001 through June 2006 and identified lesions diagnosed as ADH. The final diagnosis after surgical excision was determined from medical records. The frequencies and upgrade rates to carcinoma were calculated for all ADH lesions and compared between 9- and 11-gauge procedures. The number of core samples was recorded and compared.One hundred forty-one of 991 (14.2%) lesions yielded a diagnosis of ADH at 9- or 11-gauge stereotactic vacuum-assisted breast biopsy. Upgrade to ductal carcinoma in situ or invasive carcinoma occurred in 26 of 123 (21.1%) patients. The frequency of ADH was 83 of 600 (13.8%) lesions for 9-gauge and 58 of 391 (14.8%) lesions for 11-gauge vacuum-assisted breast biopsy. The 9-gauge upgrade rate was 16 of 74 (21.6%) lesions compared with 10 of 49 (20.4%) lesions for 11-gauge vacuum-assisted breast biopsy. There was no significant difference between the number of core samples obtained with each device (p=0.40). Neither the frequency of ADH (p=0.66) nor the upgrade rates (p=0.87) were significantly different between 9- and 11-gauge vacuum-assisted breast biopsy.Compared with an 11-gauge vacuum-assisted breast biopsy device, the use of a larger 9-gauge vacuum-assisted breast biopsy needle does not decrease the upgrade rate of ADH. Our frequency of ADH at vacuum-assisted breast biopsy is higher than any previously reported and may reflect regional differences in the incidence of breast cancer or practice patterns of the pathologist.

    View details for DOI 10.2214/AJR.08.1342

    View details for Web of Science ID 000261851600034

    View details for PubMedID 19098204

  • Impact and Outcomes of Routine Microstaging of Sentinel Lymph Nodes in Breast Cancer: Significance of the pN0(i+) and pN1mi Categories ANNALS OF SURGICAL ONCOLOGY Pugliese, M. S., Beatty, J. D., Tickman, R. J., Allison, K. H., Atwood, M. K., Szymonifka, J., Arthurs, Z. M., Huynh, P. P., Dawson, J. H. 2009; 16 (1): 113-120

    Abstract

    In 2003, the American Joint Committee on Cancer (AJCC) initiated the 6th edition staging criteria, including pN0(i+) and pN1mi categories for breast cancer. However, the clinical significance of these categories is debated in the literature.A prospective registry was used to identify patients staged with sentinel lymph node (SLN) biopsy. SLN evaluation included routine serial sectioning and immunohistochemical stains. SLN biopsies performed before January 2003 were restaged according to the AJCC's 6th edition criteria.Of 954 SLN biopsies identified, on review, 491 N0i-, 86 N0i+, 73 N1mi, 146 N1a, 29 N2a, and 11 N3a patients were available for analysis with a median follow-up of 45.4 months. Significant prognostic and therapeutic differences existed between the groups. Differences in overall survival (OS) and recurrence-free survival (RFS) were only noted when the size of the metastases reached the N1a level. There were no statistically significant differences in OS or RFS between N0(i-) and N0(i+) or N1mi disease. Cases that were N0(i+) or N1mi were more likely to have other poor prognostic factors and to receive more aggressive therapy.SLN biopsy allows a more sensitive evaluation of lymph nodes for metastatic cells. This has led to the increased identification of very small axillary metastases. While the new microstaging categories are not yet clearly associated with a significantly decreased OS or DFS in this series, they are associated with other poor prognostic factors and more local/regional and systemic therapy. Further analysis of the microstaging categories is needed.

    View details for DOI 10.1245/s10434-008-0121-x

    View details for Web of Science ID 000262555000015

    View details for PubMedID 18949520

  • Immunosuppressive regulatory T cells are associated with aggressive breast cancer phenotypes: a potential therapeutic target MODERN PATHOLOGY Bohling, S. D., Allison, K. H. 2008; 21 (12): 1527-1532

    Abstract

    FoxP3 is a marker for immunosuppressive CD25+CD4+ regulatory T cells. These regulatory T cells are thought to play a role in inducing immune tolerance to antigens and may be selectively recruited by carcinomas. We investigated whether breast carcinomas had significant numbers of FoxP3-positive regulatory T cells by immunohistochemistry, and if their presence was associated with other prognostic factors, such as Nottingham grade, hormone receptor immunohistochemical profile, tumor size, or lymph node metastases. Ninety-seven needle core or excisional breast biopsies with invasive breast carcinoma diagnosed at the University of Washington were stained with antibodies to FoxP3, estrogen receptor, and Her2/neu. The numbers of FoxP3-positive cells present within the neoplastic epithelium, and immediately adjacent stroma were counted manually in three high-powered fields (HPFs; x 400) by two independent pathologists. The average scores were then correlated with the parameters of interest. A threshold of >or=15 FoxP3-positive cells/HPF was used to define a FoxP3-positive case in some analyses. Higher average numbers of FoxP3-positive cells present significantly correlated with higher Nottingham grade status (P=0.000229). In addition, the presence of significant numbers (>or=15/HPF) of FoxP3-positive cells in breast carcinoma was positively associated with higher Nottingham grade (P=0.00002585). Higher average numbers of FoxP3-positive cells were also significantly associated with larger tumor size (>2.0 cm; P=0.012824) and trended toward an association with estrogen receptor negativity. Interestingly, 'triple-negative' (estrogen and progesterone receptor negative and Her2/neu negative) Nottingham grade III cases were also significantly associated with high numbers of FoxP3 cells. These results argue that regulatory T cells may play a role in inducing immune tolerance to higher grade, more aggressive breast carcinomas, and are a potential therapeutic target for these cancers.

    View details for DOI 10.1038/modpathol.2008.160

    View details for Web of Science ID 000261109000014

    View details for PubMedID 18820666

  • Estrogen Receptor Expression in Breast Cancer We Cannot Ignore the Shades of Gray AMERICAN JOURNAL OF CLINICAL PATHOLOGY Allison, K. H. 2008; 130 (6): 853-854

    View details for DOI 10.1309/AJCP3P3XHTCYGZIA

    View details for Web of Science ID 000260999900002

    View details for PubMedID 19019759

  • Is Surgical Excision Necessary for Focal Atypical Ductal Hyperplasia Found at Stereotactic Vacuum-Assisted Breast Biopsy? ANNALS OF SURGICAL ONCOLOGY Eby, P. R., Ochsner, J. E., DeMartini, W. B., Allison, K. H., Peacock, S., Lehman, C. D. 2008; 15 (11): 3232-3238

    Abstract

    Our goal was to determine the upgrade rate for lesions described as focal atypical ductal hyperplasia (ADH) after 9- or 11-gauge stereotactic vacuum-assisted breast biopsy (VABB) to determine whether surgical excision is indicated in this setting.We retrospectively reviewed the results of 991 consecutive 9- or 11-gauge stereotactic core VABB procedures from February 2001 through June 2006 and identified lesions diagnosed as ADH. On the basis of the descriptions in pathology reports each lesion was placed in one of three categories: (1) focal ADH, (2) ADH suspicious for ductal carcinoma-in-situ, or (3) ADH not otherwise specified. The final diagnosis after surgical excisional biopsy was determined from medical records. The frequencies and upgrade rates to carcinoma were calculated and compared for all lesions and for each ADH category.A total of 141 (14.2%) of 991 lesions yielded ADH at stereotactic core VABB, and 123 (87.2%) of 141 underwent surgical excisional biopsy of the stereotactic core VABB site. A total of 56 (45.5%) of 123 were categorized as focal ADH, and 7 (12.5%) of 56 were upgraded to carcinoma. A total of 49 (39.8%) of 123 were categorized as ADH not otherwise specified, and 11 (22.4%) of 49 were upgraded. Eighteen (14.6%) of 123 were categorized as suspicious for ductal carcinoma-in-situ, and 8 (44.4%) of 18 were upgraded. Neither the frequency of ADH (P = .66) nor the upgrade rates (P = .87) were significantly different between 9- and 11-gauge VABB.Surgical excisional biopsy is indicated to exclude carcinoma in cases of focal ADH discovered at 9- or 11-gauge VABB.

    View details for DOI 10.1245/s10434-008-0100-2

    View details for Web of Science ID 000260509400034

    View details for PubMedID 18696163

  • Immunohistochemical markers in endometrial hyperplasia: Is there a panel with promise? A review APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY Allison, K. H., Tenpenny, E., Reed, S. D., Swisher, E. M., Garica, R. L. 2008; 16 (4): 329-343

    Abstract

    Despite advances in defining the biology of endometrial carcinomas, there has been little progress in determining markers that distinguish preinvasive endometrial proliferations. The goal of this literature review was to identify studies on endometrial hyperplasia (EH) that describe markers with potential to predict response to progestin therapy or potential for progression to invasive disease.Articles published between January 2000 and October 2006 were identified using the key words endometrial hyperplasia and progesterone receptor or estrogen receptor or biologic marker or immunohistochemistry/immunohistochemical. Articles that reported immunohistochemical studies on specimens of human EH +/-endometrioid endometrial carcinoma with a normal comparison group were included. Only those who reported hyperplasia with atypia separately from nonatypical hyperplasia and with a sample size greater than 10 specimens for the sum of complex and atypical samples were included.A total of 289 abstracts were reviewed and 150 articles potentially met inclusion criteria. Of these, 123 described immunohistochemical studies on human EH specimens. Only 46 met all criteria for analysis of 61 different markers.PTEN seems to have the greatest potential for diagnostic utility in EH, perhaps in combination with Bcl-2 and Bax. However, more uniform and rigorous studies are required to confirm these and additional markers' utility diagnostically in a diagnostic panel. As a major clinical priority is to determine which lesions can be treated medically and which require surgical intervention, focusing future studies on markers that distinguish response to hormone therapy or are involved in hormone regulation, will be important future considerations.

    View details for Web of Science ID 000257270100006

    View details for PubMedID 18528284

  • Intratumoral T cells, tumor-associated macrophages, and regulatory T cells: Association with p53 mutations, circulating tumor DNA and survival in women with ovarian cancer GYNECOLOGIC ONCOLOGY Shah, C. A., Allison, K. H., Garcia, R. L., Gray, H. J., Goff, B. A., Swisher, E. M. 2008; 109 (2): 215-219

    Abstract

    Forty percent of women with ovarian cancer have circulating free tumor DNA. We sought to determine if the tumor immune infiltrate varied based on tumor p53 mutation status or presence of circulating tumor DNA.We performed immunohistochemistry on 119 ovarian cancer specimens with CD3 and CD8 (Intratumoral T cells (TILs)), CD68 (tumor-associated macrophages (TAMs)), and FoxP3 (T regulatory cells (Tregs)). Tumors had been previously sequenced for mutations in exons 4-10 of p53, and plasma from women characterized for free tumor DNA.TIL and TAM levels were positively correlated (P<0.0001). High levels of TILs were identified in 54 of 119 tumors (45.4%). No survival difference was identified according to the presence of TILs or TAMs. Patients with greater TILs were more likely to be optimally cytoreduced (P=0.005). p53 mutations were associated with more TILs (P=0.008). The presence of circulating tumor DNA did not correlate with TILs, TAMs, or Tregs. In the subgroup with a low host antitumor immune response, the intermediate response Tregs group did have a survival advantage (P=0.049).p53 mutations are associated with higher levels of TILs. The ratio of Tregs to TILS may be more important than absolute levels. A brisk T cell response within the tumor predicts adequacy of cytoreduction, suggesting successful cytoreduction may be partially due to underlying tumor biology and host response.

    View details for DOI 10.1016/j.ygyno.2008.01.010

    View details for Web of Science ID 000256205600012

    View details for PubMedID 18314181

  • Diagnosing endometrial hyperplasia - Why is it so difficult to agree? AMERICAN JOURNAL OF SURGICAL PATHOLOGY Allison, K. H., Reed, S. D., Voigt, L. F., Jordan, C. D., Newton, K. M., Garcia, R. L. 2008; 32 (5): 691-698

    Abstract

    Current World Health Organization classification of endometrial hyperplasia is problematic because of poor diagnostic reproducibility. We sought to determine factors that cause diagnostic disagreement in a review of 2601 endometrial specimens. Blinded random specimens of normal endometrium, hyperplasias, and carcinoma were reviewed by 2 pathologists, with review by a third pathologist in cases with disagreement. All cases of endometrial hyperplasia or carcinoma were scored for degree of glandular crowding, architectural complexity, and cytologic atypia. Sample adequacy, hyperplasia volume, presence of metaplasia, or endometrial polyp were also scored. The overall kappa for agreement was 0.71, with a lower kappa of 0.36 when cases called "no hyperplasia" were excluded. The percent specific agreement was 90.3% for no hyperplasia, 31.1% for simple hyperplasia, 51.1% for complex hyperplasia, 49.8% for atypical hyperplasia, and 57.5% for adenocarcinoma. Cases categorized as "low volume hyperplasia" had more diagnostic disagreement than "high volume," (62% vs. 39%, P=0.003). Similarly, cases called "scant" had more diagnostic disagreement than "not scant" (65% vs. 57%, P=0.013). The histologic feature associated with the most diagnostic disagreement was cytologic atypia (P<0.0001). Architectural crowding, architectural complexity, or the presence of a polyp were all associated with diagnostic disagreement (P<0.0001). High diagnostic disagreement in endometrial hyperplasia is related to both sample adequacy and interpretation of histologic features present. Although obtaining additional tissue may increase diagnostic reproducibility, differences in interpretation of key histologic features like cytologic atypia remain major factors contributing to diagnostic disagreement.

    View details for Web of Science ID 000255559800005

    View details for PubMedID 18347507

  • Defining an appropriate threshold for the diagnosis of serous borderline tumor of the ovary: When is a full staging procedure unnecessary? INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY Allison, K. H., Swisher, E. M., Kerkering, K. M., Garcia, R. L. 2008; 27 (1): 10-17

    Abstract

    How much borderline change in an otherwise typical ovarian serous cystadenoma should warrant classification as a serous ovarian "borderline tumor?" We correlated estimated volume and percent borderline change with stage in 56 cases of serous ovarian neoplasms (excluding carcinomas) diagnosed as at least focal borderline change to see if we could define an appropriate threshold for the diagnosis of borderline tumor that would justify full surgical staging. Forty-three cases were completely staged, 6 had "fertility-sparing" but otherwise complete staging, and 7 cases had "limited" staging. Thirty-eight cases were stage 1a-1c, and 18 were greater than stage 1. Cases with stage 1 disease had a significantly lower mean volume of borderline change sampled of 2.0 compared with 5.6 cm in cases with greater than stage 1 disease (P = 0.0002). All high-stage cases had at least 1.0 cm or more of borderline change sampled (range, 1.0-12). Cases with stage 1 disease had a significantly lower mean estimated total percent borderline change of 34.8% compared with 77.2% in cases with greater than stage 1 disease (P < 0.0001). All high-stage cases had 20% or more total borderline change (range, 20%-100%). In addition, a grossly exophytic growth pattern component was highly predictive of high stage (P < or = 0.0001). Two cases recurred-both were advanced-stage and high-percent borderline change. There were no deaths due to disease (mean follow-up, 85 months). Our study supports a conservative 10% cutoff for classification as a "borderline tumor," and that complete surgical staging is not necessary when a serous neoplasm with an intracystic growth pattern has less than 10% or 0.5-cm borderline change.

    View details for DOI 10.1097/pgp.0b013e318133a9b7

    View details for Web of Science ID 000252124400002

    View details for PubMedID 18156968

  • Alternate molecular genetic pathways in ovarian carcinomas of common histological types HUMAN PATHOLOGY Willner, J., Wurz, K., Allison, K. H., Galic, V., Garcia, R. L., Goff, B. A., Swisher, E. M. 2007; 38 (4): 607-613

    Abstract

    We evaluated alterations in p53, PIK3CA, PTEN, CTNNB1 (beta-catenin), MLH1, and BRAF among common histological subsets of epithelial ovarian tumors to characterize patterns of alterations of different molecular pathways. There were 12 clear cell, 26 endometrioid, and 51 serous carcinomas evaluated by direct DNA sequencing for mutations in p53, PIK3CA, PTEN, BRAF, and CTNNB1. Methylation-specific polymerase chain reaction (PCR) assessed MLH1 promoter methylation status. Quantitative PCR identified PIK3CA amplification in 22 EC/CC and 94 SC. p53 mutations were identified in 25 (49%) of 51 SC, 11 (42%) of 26 EC, and 1 (8.3%) of 12 CC neoplasms and were more common in grade 3 EC (P = .045) and advanced-stage EC/CC (P = .007). PIK3CA mutations were identified in 3 (25%) of 12 CC, 3 (12%) of 26 EC, and 0 of 51 SC. PTEN mutations were significantly more common in EC (8/26, 31%) compared with CC (0/12; P = .04) and SC (2/51, 4%; P = .002). CTNNB1 mutations were identified, 6 (23%) EC and no CC or SC (P = .008). Both PTEN and CTNNB1 mutations were more common in low-grade EC/CC, whereas PIK3CA mutations occurred only in grade 3 cancers. PTEN and PIK3CA mutations were more common in p53 wild-type tumors (P = .003). PIK3CA amplification occurred in fewer EC/CC (0/22) versus SC (19/94, 20%; P = 0.02) and were slightly more common in p53 wild-type compared with p53 mutant SC (P = .08). Of 26 EC, 22 (85%) had a mutation in one of the genes studied compared with 4 33% of 12 CC (P = .003). Women with EC/CC had significantly better overall survival (P = .0008), and this remained significant after accounting for stage (P=.04). Mutations in p53 or in PTEN/PIK3CA are alternative pathways in ovarian carcinogenesis. Activation of PIK3CA occurs by gene amplification in SC but via somatic mutation of PIK3CA or PTEN in EC and CC. PIK3CA mutations are associated with high-grade tumors, whereas PTEN and CTNNB1 mutations are associated with low-grade tumors. Mutations in p53, PIK3CA, PTEN, and CTNNB1 account for most EC tumors; most CC remain unexplained. EC/CC histology is a favorable prognostic factor.

    View details for DOI 10.1016/j.humpath.2006.10.007

    View details for Web of Science ID 000245319800011

    View details for PubMedID 17258789

  • Epithelioid trophoblastic - Tumor review of a rare neoplasm of the chorionic-type intermediate trophoblast ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE Allison, K. H., Love, J. E., Garcia, R. L. 2006; 130 (12): 1875-1877

    Abstract

    We present a brief review of epithelioid trophoblastic tumor, a rare trophoblastic neoplasm derived from chorionic-type intermediate trophoblastic cells that typically presents in reproductive-age women between 1 and 18 years following a previous gestation. Histologic features include a nodular growth pattern of monomorphic, epithelioid cells within a hyaline matrix. Areas of necrosis and mitotic activity (0-9 mitoses per 10 high-power fields) are additional features of this neoplasm. Positive immunostaining for p63 and cytokeratin, frequent location in the lower uterine segment and endocervix, as well as the epithelioid appearance can lead to confusion with squamous cell carcinoma. Inhibin-alpha is typically expressed, as well as focal, more variable expression of other trophoblastic markers including beta-human chorionic gonadotropin, human placental lactogen, placental alkaline phosphate, and Mel-CAM (CD148). The clinical behavior of this rare form of gestational trophoblastic disease is difficult to predict. Although most cases follow a benign course following resection, there is a potential for metastatic disease.

    View details for Web of Science ID 000242645000030

    View details for PubMedID 17149967

  • Accuracy of intraoperative imprint cytology of sentinel lymph nodes in breast cancer AMERICAN JOURNAL OF SURGERY Pugliese, M. S., Kohr, J. R., Allison, K. H., Wang, N. P., Tickman, R. J., Beatty, J. D. 2006; 192 (4): 516-519

    Abstract

    In breast cancer treatment, immediate completion of axillary lymph node dissection (ALND) can be performed if the intraoperative sentinel lymph node (SLN) examination is positive. This study evaluates the accuracy of intraoperative imprint cytology (IC) for detecting SLN metastases.Pathology reports from 385 SLN biopsy examinations were reviewed retrospectively. The SLNs were serially sectioned perpendicular to the long axis and IC was performed intraoperatively. The SLNs then were formalin-fixed for permanent sections. Final pathology was compared with the intraoperative IC results.The sensitivities for IC detection of N0(i+) (n = 36), N1mi (n = 24), and N1a-3a (n = 65) metastases were 0%, 4%, and 74%, respectively. The specificity was 100%.Final pathology identified 89 (23%) patients with N1 or greater disease. IC allowed 49 (55%) of these patients to undergo synchronous completion of ALND. No unnecessary completion ALNDs were performed. The sensitivity of IC decreased with decreasing size of the metastasis.

    View details for DOI 10.1016/j.amjsurg.2006.05.014

    View details for Web of Science ID 000240750800026

    View details for PubMedID 16978964

  • Can an immunoassay become a standard technique in detecting oxycodone and its metabolites? JOURNAL OF ANALYTICAL TOXICOLOGY Abadie, J. M., Allison, K. H., Black, D. A., Garbin, J., Saxon, A. J., Bankson, D. D. 2005; 29 (8): 825-829

    Abstract

    Opiate toxicology testing is routinely performed in the hospital setting to identify abusers and/or to determine those patients who are not taking prescribed opiate analgesics such as oxycodone. Commercially available assays for opiate detection in urine have decreased sensitivity for oxycodone, which contributes to a high false-negative rate. Functioning as a beta site, our Veterans Affairs hospital evaluated a new enzyme immunoassay, DRI Oxycodone Assay, for its use in the qualitative and semiquantitative detection of oxycodone in urine. We hypothesize that an immunoassay for oxycodone with superior sensitivity and specificity, when compared to the traditional opiate assays, would reduce the need for more expensive and time-consuming confirmatory testing. We used the new liquid homogenous enzyme immunoassay to determine oxycodone results in a total of 148 urine samples from 4 different sample groups. Gas chromatography-mass spectroscopy was subsequently used to confirm the presence or absence of oxycodone (or its primary metabolite, noroxycodone). We also evaluated within-run, between-run, and linearity studies and conducted a crossover study to establish a cutoff value for oxycodone. In our patient population, we used the new DRI immunoassay to evaluate 17,069 urine samples to estimate oxycodone misuse profiles (patients not taking prescribed oxycodone or taking oxycodone without a prescription) during a 4-month period. The sensitivity and specificity of the new oxycodone immunoassay were 97.7% and 100%, respectively, at the cutoff concentration of 300 ng/mL. The assay linearity was 1,250 ng/mL, and the sensitivity was 10 ng/mL. Within-run precision and between-run coefficient of variation were 2.3% and 1.8%, respectively. None of the 15 compounds that we evaluated for interference had crossover significant enough to produce a positive oxycodone result when using 300 ng/mL as the cutoff value. None of the 17,069 oxycodone immunoassays was followed with a request for confirmation. Among patients with positive results (n = 224), 93 (41.5%) were not prescribed oxycodone. The new DRI Oxycodone Assay is a sensitive and specific screening test for the determination of oxycodone. The improved opiate screening results may lead to better patient and prescription management, to decreased laboratory spending, and to the identification of oxycodone abusers, which could result in decreased oxycodone-related mortality.

    View details for Web of Science ID 000233448800011

    View details for PubMedID 16374942

  • Superficial malignant peripheral nerve sheath tumor - A rare and challenging diagnosis AMERICAN JOURNAL OF CLINICAL PATHOLOGY Allison, K. H., Patel, R. M., Goldblum, J. R., Rubin, B. P. 2005; 124 (5): 685-692

    Abstract

    We reviewed the clinicopathologic features of 5 cases of malignant peripheral nerve sheath tumor (MPNST) manifesting in superficial locations associated with cutaneous neurofibromas (4 cases) or superficial peripheral nerve (1 case). Four cases had spindle cell morphologic features and were at least focally positive for S-100 protein, whereas the associated benign neural elements had more extensive S-100 immunoreactivity. The single epithelioid case was diffusely and strongly positive for S-100 protein. Melanoma markers, epithelial membrane antigen, glial fibrillary acidic protein, neurofilament, pancytokeratin (AE1/AE3), CD34, smooth muscle actin, and desmin were negative in all cases. There were no local recurrences, but 3 patients died of metastatic disease within 2 to 30 months (median, 21 months). MPNSTs can occur in a superficial location and may have an aggressive clinical course. Immunohistochemical markers are helpful in excluding other lesions in the differential diagnosis. However, identification of a benign precursor or origin from a nerve may be the most definitive way to properly classify these rare lesions.

    View details for DOI 10.1309/VBXMK5R78O96V090

    View details for Web of Science ID 000232836500003

    View details for PubMedID 16203275

  • Radiographically occult, diffuse intrasinusoidal hepatic metastases from primary breast carcinomas - A clinicopathologic study of 3 autopsy cases ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE Allison, K. H., Fligner, C. L., Parks, T. 2004; 128 (12): 1418-1423

    Abstract

    Liver metastases usually present as radiographically detectable mass lesions that do not significantly compromise liver function. Rarely, metastatic carcinoma can diffusely infiltrate hepatic sinusoids, a pattern of metastasis that may be missed on imaging studies, and can result in liver failure.To describe the clinicopathologic features of 3 cases of diffuse intrasinusoidal hepatic metastases from primary breast carcinomas identified at autopsy.Clinical histories and radiographic, macroscopic, and microscopic appearances of the livers were compared. Sampled liver tissue was stained with antibodies to E-cadherin, smooth muscle actin, and CD44.Two of 3 cases had a history of infiltrating ductal carcinoma of the breast and presented with new-onset liver failure, but no hepatic metastases were identified on radiologic imaging. An additional case had no history of carcinoma, presented with a severe thrombocytopenic thrombotic purpura-like syndrome, and metastatic carcinoma of the breast was diagnosed only at autopsy. The livers in all 3 cases at autopsy were homogeneous, firm, and tan-yellow, and contained no large metastatic lesions. Microscopically, poorly differentiated carcinoma diffusely infiltrated hepatic sinusoids. Antibodies to smooth muscle actin stained activated hepatic stellate cells lining involved sinusoids. Cell surface adhesion molecules, E-cadherin or CD44, were not detected in any hepatic metastases.Diffuse intrasinusoidal hepatic metastases of breast carcinoma can occupy a large percentage of the hepatic volume, yet remain occult both radiographically and macroscopically. This type of metastatic spread can present as cryptogenic liver failure. The 3 cases we studied were associated with an absence of E-cadherin and CD44 expression.

    View details for Web of Science ID 000225720100023

    View details for PubMedID 15578887

  • Angiosarcoma involving the gastrointestinal tract - A series of primary and metastatic cases AMERICAN JOURNAL OF SURGICAL PATHOLOGY Allison, K. H., Yoder, B. J., Bronner, M. P., Goldblum, J. R., Rubin, B. P. 2004; 28 (3): 298-307

    Abstract

    Angiosarcoma occurs very rarely in the intestinal tract as either a primary or metastatic malignancy and can present great diagnostic difficulty, especially when it displays epithelioid cytomorphology. Since only isolated case reports have been published, the purpose of this study is to more fully delineate the histopathological and clinical features from a series of 8 angiosarcomas involving the gastrointestinal tract. There were 5 male and 3 female patients whose ages ranged from 25-85 years (median 57). Presenting symptoms included intestinal bleeding, anemia and pain. Five cases involved the small bowel and 3 involved the colon/rectum. Four cases were primary to the intestinal tract, 2 patients initially presented with secondary involvement of the large bowel from occult retroperitoneal primaries, 1 patient presented with disseminated disease including small bowel involvement, and 1 case was metastatic from a breast primary. Seven cases were composed predominantly of sheets of malignant appearing epithelioid cells with subtle areas forming cleft-like spaces suggestive of vascular differentiation. Immunohistochemical studies revealed the lesional cells to be immunoreactive for CD31 (8/8), CD34 (8/8), Factor VIII (8/8), cytokeratins AE1/AE3 (7/8), cytokeratin 7 (2/8), Cam5.2/cytokeratin 8 (5/8), and cytokeratin 19 (5/8). Cytokeratin 20 was negative in all eight cases, which contrasts sharply with the characteristic positivity for cytokeratin 20 in virtually all intestinal carcinomas. One case was weakly and focally positive for EMA and all cases were negative for S-100 protein. Cytokeratin staining was variable and ranged from focal to extensive. Follow-up was available in eight cases and ranged from 1-33 months (median 12.5). Five patients died of disease, between 1 and 33 months (median 6) after diagnosis. One recently diagnosed patient is alive with disease 18 months after diagnosis, and one patient is free of disease 27 months after original diagnosis. Angiosarcomas of the gastrointestinal tract commonly display epithelioid cytomorphology, may be diffusely and strongly positive for cytokeratins and only show subtle signs of vascular differentiation, creating potential diagnostic confusion with primary or metastatic carcinoma. Given the clinically aggressive behavior of angiosarcoma, proper classification and treatment is important. Immunohistochemistry with vascular markers, CK20, and S-100 protein may be helpful in differentiating angiosarcoma from carcinoma and melanoma.

    View details for Web of Science ID 000189316500002

    View details for PubMedID 15104292

  • An unusual case of multiple giant myelolipomas: Clinical and pathogenetic implications ENDOCRINE PATHOLOGY Allison, K. H., Mann, G. N., Norwood, T. H., Rubin, B. P. 2003; 14 (1): 93-100

    Abstract

    Myelolipomas are benign tumors composed of both mature adipose and myeloid tissues. They typically present as an incidental mass in one of the adrenal glands proper. However, they can occur in ectopic adrenal tissue or, rarely, without associated adrenal tissue in various locations and can grow to weights of several kilograms. These tumors have been linked to endocrinopathies, such as Cushing disease and congenital adrenal hyperplasia, which involve overproduction of adrenocorticotropic hormone. We report a case of three giant adrenal myelolipomas arising in a persistently virilized female with congenital adrenal hyperplasia, supporting a role for hormonal stimuli in myelolipoma formation.

    View details for Web of Science ID 000183026300010

    View details for PubMedID 12746567

Stanford Medicine Resources: