Publications by authors named "Julie M Jorns"

51 Publications

Assessing the value of second opinion pathology review.

Int J Qual Health Care 2021 Mar;33(1)

Department of Pathology, Medical College of Wisconsin, 9200 W. Wisconsin Avenue, Lab Building, Lower Level, Room L69, Milwaukee, WI 53226, USA.

Background: Second opinion review of pathology cases can identify diagnostic errors that impact patient care.

Objective: We sought out to determine discrepancy rates and clinical impact of review of pathology cases to reassess our policy of review on all second opinion cases.

Methods: All second opinion pathology cases over 1 year (2018) were retrospectively reviewed for discrepancy, multiple pathologist review and clinicopathologic features via chart and slide review. Cases were categorized as no significant discordance, major discordance without management change and major discordance with management change.

Results: Among 4239 second opinion cases, 3.7% (156/4239) had major discordance with no change in management and 1% (42/4239) had major discordance with change in management. Discordance was significantly associated with multiple pathologist review at our institution (P < 0.001). Highest rates of discordance were observed for thyroid fine needle aspiration (15.3%, 26/170), tissue biopsy of bone/soft tissue (9.6%), endocrine (8.8%), genitourinary (6.7%), gynecologic (6.2%), hematopathology (4%), gastrointestinal/liver (3.7%) and thoracic (3%) sites.

Conclusions: Our study showed a 1% major discordance rate with resulting significant change in clinical management, spread across nearly all subspecialties. Thus, we support recommendations for review of relevant outside pathology material for all patients for which review has the potential to illicit management change such as instituting a major medical or surgical therapy.
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http://dx.doi.org/10.1093/intqhc/mzab032DOI Listing
March 2021

Cytokeratin 7, GATA3, and SOX-10 is a Comprehensive Panel in Diagnosing Triple Negative Breast Cancer Brain Metastases.

Int J Surg Pathol 2021 Feb 5:1066896921990717. Epub 2021 Feb 5.

5506Medical College of Wisconsin, Milwaukee, WI, USA.

Following lung cancer, breast cancer is the second most common metastatic tumor to the brain, of which triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2+ (HER2+) breast cancer are the most common subtypes. TNBC does not have standard immunoprofiles and can be difficult to distinguish from other metastases. A tissue microarray was created from 47 patients with breast cancer metastases to the brain and 12 paired breast primaries. Of 47 breast cancer metastases, 24 were HER2+, 14 were TNBC, and 9 were luminal. Forty-five were cytokeratin 7 (CK7) positive, 36 were GATA-binding protein 3 (GATA3) positive, 7 were Sry-related HMg-Box gene 10 (SOX-10) positive, 20 were mammaglobin positive, and 19 were gross cystic disease fluid protein 15 positive. At least one of the CK7, GATA3, or SOX-10 was positive in all TNBC metastases. A panel of CK7, GATA3, and SOX-10 is complementary in the diagnosis of breast cancer brain metastasis. SOX-10 appears to be a specific but not particularly sensitive marker in this context.
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http://dx.doi.org/10.1177/1066896921990717DOI Listing
February 2021

Rapid assessment of breast tumor margins using deep ultraviolet fluorescence scanning microscopy.

J Biomed Opt 2020 11;25(12)

Marquette University and Medical College of Wisconsin, Department of Biomedical Engineering, Milwauk, United States.

Significance: Re-excision rates for women with invasive breast cancer undergoing breast conserving surgery (or lumpectomy) have decreased in the past decade but remain substantial. This is mainly due to the inability to assess the entire surface of an excised lumpectomy specimen efficiently and accurately during surgery.

Aim: The goal of this study was to develop a deep-ultraviolet scanning fluorescence microscope (DUV-FSM) that can be used to accurately and rapidly detect cancer cells on the surface of excised breast tissue.

Approach: A DUV-FSM was used to image the surfaces of 47 (31 malignant and 16 normal/benign) fresh breast tissue samples stained in propidium iodide and eosin Y solutions. A set of fluorescence images were obtained from each sample using low magnification (4  ×  ) and fully automated scanning. The images were stitched to form a color image. Three nonmedical evaluators were trained to interpret and assess the fluorescence images. Nuclear-cytoplasm ratio (N/C) was calculated and used for tissue classification.

Results: DUV-FSM images a breast sample with subcellular resolution at a speed of 1.0  min  /  cm2. Fluorescence images show excellent visual contrast in color, tissue texture, cell density, and shape between invasive carcinomas and their normal counterparts. Visual interpretation of fluorescence images by nonmedical evaluators was able to distinguish invasive carcinoma from normal samples with high sensitivity (97.62%) and specificity (92.86%). Using N/C alone was able to differentiate patch-level invasive carcinoma from normal breast tissues with reasonable sensitivity (81.5%) and specificity (78.5%).

Conclusions: DUV-FSM achieved a good balance between imaging speed and spatial resolution with excellent contrast, which allows either visual or quantitative detection of invasive cancer cells on the surfaces of a breast surgical specimen.
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http://dx.doi.org/10.1117/1.JBO.25.12.126501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688317PMC
November 2020

Breast Sentinel Lymph Node Frozen Section Practice: An Enterprise Audit as a Guide for Moving Forward.

Arch Pathol Lab Med 2020 Nov 19. Epub 2020 Nov 19.

From the Departments of Pathology (Czaja, Jorns).

Context.—: In recent years, there has been a shift to less aggressive surgical management of the axilla in breast cancer. Consequently, sentinel lymph node evaluation by frozen section (FS) has declined. Additionally, there has been an impetus to decrease efforts in identifying small sentinel lymph node metastases.

Objectives.—: To critically evaluate our enterprise performance in evaluating axillary sentinel lymph node submitted for FS prior to considering changes in processing.

Design.—: A retrospective review (August 1, 2017-July 31, 2019) was conducted to identify sentinel and nonsentinel lymph nodes from 1 academic institution and 2 community sites. Cases were evaluated for grossing technique and discordance between FS and permanent section (PS) due to sampling and/or interpretive error. Clinicopathologic features were assessed.

Results.—: Lymph nodes from 426 patients with 432 neoplasms were sent for FS. Serial sectioning at 2-mm intervals was adhered to in 338 of 432 (78.2%). Serial sectioning was significantly lower at the community sites (14 of 60; 23.3%) versus at the academic institution (324 of 372; 87.1%; P < .001). Discordant cases were all false negatives (21 of 432; 4.8%). A total of 7 of 21 false negatives (33.3%) had macrometastatic (>2 mm) disease; of these, 3 were post-neoadjuvant chemotherapy, 3 were neither serially sectioned nor posttherapy, and 1 was a small (0.3-cm) focus. A total of 15 of 16 false negatives due to sampling error were detected on the first permanent section level.

Conclusions.—: Standard serial sectioning of sentinel lymph node at 2-mm intervals resulted in infrequent false negatives due to macrometastatic disease. A single additional permanent section level is reasonable, given adherence to serial sectioning.
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http://dx.doi.org/10.5858/arpa.2020-0411-OADOI Listing
November 2020

Data-Driven Development of an Institutional "Gross-Only" Policy for the Examination of Select Surgical Pathology Specimens.

Am J Clin Pathol 2020 09;154(4):486-493

Medical College of Wisconsin, Department of Pathology, Milwaukee.

Objectives: To determine diagnostic, workflow, and economic implications of instituting a gross-only policy at our institution.

Methods: Retrospective (2017) key word searches were performed to identify "gross-only" cases for which microscopic evaluation could potentially be omitted, but was performed, and those who underwent gross evaluation per surgeon request. Cases were evaluated for type(s), part(s), block volume, turnaround time, demographics, and diagnosis. Laboratory costs and reimbursement were evaluated.

Results: In total, 448 potential gross-only cases with 472 specimens consisted of atherosclerotic plaques (33.5%), bariatric stomach/bowel (32.6%), hernia (15.7%), heart valves (12.7%), and other (5.9%). Four (2.6%) bariatric surgery cases had Helicobacter pylori infection; these were the only cases with "significant" histologic findings. Cost analysis revealed that converting all potential gross-only specimens to gross only would result in overall losses based on average reimbursements, most influenced by bariatric specimens (Current Procedural Terminology code 88307), comprising 65.2% of estimated loss.

Conclusions: Establishing a gross-only policy should be guided by established recommendations but institutionally individualized and data driven. It was reasonable for us to establish a gross-only policy for most evaluated specimens, while excluding bariatric stomach specimens in which microscopic pathology could be missed, given the lack of H pylori screening at our institution.
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http://dx.doi.org/10.1093/ajcp/aqaa065DOI Listing
September 2020

Benign vascular lesions and angiolipomas of the breast: Radiologic-pathologic correlation.

Breast J 2020 09 12;26(9):1906-1908. Epub 2020 Mar 12.

Departments of Pathology, Medical College of Wisconsin, Milwaukee, Wisconsin.

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http://dx.doi.org/10.1111/tbj.13805DOI Listing
September 2020

Lymphocytic mastitis mimicking breast cancer in an elderly woman.

Breast J 2020 07 7;26(7):1414-1415. Epub 2020 Feb 7.

Department of Pathology, Medical College of Wisconsin, Milwaukee, WI, USA.

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http://dx.doi.org/10.1111/tbj.13774DOI Listing
July 2020

A high mitotic score in breast cancer after neoadjuvant chemotherapy is predictive of outcome and associated with a distinct morphology.

Histopathology 2020 Apr 17;76(5):661-670. Epub 2020 Mar 17.

Department of Pathology, Medical College of Wisconsin, Milwaukee, WI, USA.

Aims: Neoadjuvant chemotherapy (NAC) is frequently used for the treatment of breast cancer. We sought to analyse the clinical, morphological and immunohistochemical features of tumours from patients who did not achieve pathological complete response following NAC.

Methods And Results: We identified stage I-III post-NAC breast cancers from surgical resections (2000-2016) with evaluable residual invasive carcinoma [ypT1a(m) or greater and ≥15% tumour cellularity]. One hundred and forty-three tumours from 142 patients were included. On univariable analysis, a high (score 3) post-NAC mitotic score (as compared with 1 or 2) was significantly associated with invasive ductal carcinoma (IDC) subtype (P = 0.023), high grade, pushing borders with zones of necrosis, hormone receptor and triple-negative status, lack of hormonal therapy, higher cellularity (P < 0.001), and a higher percentage of tumour-infiltrating lymphocytes (P = 0.016). Multivariable analysis showed a high post-NAC mitotic score to be significantly associated with recurrence, distant metastasis, and shortened survival (hazard ratios of 5.73, 4.49, and 3.68, respectively). High post-NAC mitotic score tumours (n = 32) were IDC and had a high Ki67 proliferation index (median, 55%). Of these, 24 (75%) had pushing borders with zones of necrosis; 19 (79.2%) of these had necrosis on preoperative imaging, and 24 (75%), 15 (46.9%) and four (12.5%) lacked androgen receptor, GATA-3 and cytokeratin 18 expression, respectively.

Conclusions: High post-NAC mitotic score breast cancers cause high morbidity and mortality, frequently have pushing borders and zones of necrosis, and may show loss of common 'breast cancer markers'. Our findings support that necrosis in pretreatment studies and post-NAC mitotic score should be routinely reported, as they offer significant additional prognostic information to guide management.
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http://dx.doi.org/10.1111/his.14049DOI Listing
April 2020

Interaction of tumor cells and astrocytes promotes breast cancer brain metastases through TGF-β2/ANGPTL4 axes.

NPJ Precis Oncol 2019 3;3:24. Epub 2019 Oct 3.

1Department of Obstetrics & Gynecology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226 USA.

Metastatic outcomes depend on the interactions of metastatic cells with a specific organ microenvironment. Our previous studies have shown that triple-negative breast cancer (TNBC) MDA-MB-231 cells passaged in astrocyte-conditioned medium (ACM) show proclivity to form brain metastases, but the underlying mechanism is unknown. The combination of microarray analysis, qPCR, and ELISA assay were carried out to demonstrate the ACM-induced expression of angiopoietin-like 4 (ANGPTL4) in TNBC cells. A stable -knockdown MDA-MB-231 cell line was generated by short-hairpin RNA (shRNA) and inoculated into mice via left ventricular injection to evaluate the role of ANGPTL4 in brain metastasis formation. The approaches of siRNA, neutralizing antibodies, inhibitors, and immunoprecipitation were used to demonstrate the involved signaling molecules. We first found that ACM-conditioned TNBC cells upregulated the expression of ANGPTL4, a secreted glycoprotein whose effect on tumor progression is known to be tumor microenvironment- and tumor-type dependent. Knockdown of ANGPTL4 in TNBC MDA-MB-231 cells with shRNA decreased ACM-induced tumor cell metastatic growth in the brain and attributed to survival in a mouse model. Furthermore, we identified that astrocytes produced transforming growth factor-beta 2 (TGF-β2), which in part is responsible for upregulation of ANGPTL4 expression in TNBC through induction of SMAD signaling. Moreover, we identified that tumor cells communicate with astrocytes, where tumor cell-derived interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) increased the expression of TGF-β2 in astrocytes. Collectively, these findings indicate that the invading TNBC cells interact with astrocytes in the brain microenvironment that facilitates brain metastases of TNBC cells through a TGF-β2/ANGPTL4 axis. This provides groundwork to target ANGPTL4 as a treatment for breast cancer brain metastases.
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http://dx.doi.org/10.1038/s41698-019-0094-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776663PMC
October 2019

Endosalpingiosis and other benign epithelial inclusions in breast sentinel lymph nodes.

Breast J 2020 02 11;26(2):274-275. Epub 2019 Sep 11.

Department of Pathology, Medical College of Wisconsin, Milwaukee, WI, USA.

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http://dx.doi.org/10.1111/tbj.13539DOI Listing
February 2020

Breast Cancer Biomarkers: Challenges in Routine Estrogen Receptor, Progesterone Receptor, and HER2/neu Evaluation.

Authors:
Julie M Jorns

Arch Pathol Lab Med 2019 12 2;143(12):1444-1449. Epub 2019 Aug 2.

From the Department of Pathology, Medical College of Wisconsin, Milwaukee.

Context.—: Evaluation of estrogen receptor (ER), progesterone receptor (PR), and HER2/neu (HER2) biomarkers is standard of care for all cases of newly diagnosed invasive, recurrent, and metastatic breast cancer. Repeat analysis is also performed in select cases per College of American Pathologists/American Society of Clinical Oncology guidelines and other clinical indications. However, in specific scenarios, preanalytic and analytic variables may pose distinct challenges to testing.

Objective.—: To provide a review of select challenges in the testing of commonly performed breast cancer biomarkers ER, PR, and HER2 and outline best practices for overcoming these challenges.

Data Sources.—: Review of College of American Pathologists/American Society of Clinical Oncology recommendations, current literature, and personal experience of the author.

Conclusions.—: Attention must be given to specimen handling to ensure accurate ER, PR, and HER2 biomarker assessment and appropriate management of breast cancer patients.
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http://dx.doi.org/10.5858/arpa.2019-0205-RADOI Listing
December 2019

Repeat Biomarker Status in Breast Resection Specimens With Controlled Cold Ischemic Time.

Am J Clin Pathol 2019 11;152(6):766-774

Department of Pathology, Medical College of Wisconsin, Milwaukee.

Objectives: Current College of American Pathologists/American Society of Clinical Oncology guidelines recommend cold ischemic time (CIT) of 1 hour or less for breast specimens to preserve biomarker expression, although some publications support an acceptable CIT of 4 hours or less. We retrospectively evaluated changes in estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) from biopsy to resection specimens that were triaged to optimize CIT.

Methods: We identified breast resection specimens collected after institutional implementation of a triage protocol. Clinicopathologic features were assessed.

Results: In total, 295 excisions had a prior malignant diagnosis, with CIT of 4 hours or less and repeat ER, PR, and/or HER2; 230 (78%) had CIT of 1 hour or less, and 65 (22%) had CIT of more than 1 hour but 4 hours or less. Categorical change was seen in 10 (17.9%) of 56 with repeated ER/PR and 38 (13.3%) of 285 with repeated HER2 (of which five [1.8%] had meaningful change).

Conclusions: When CIT is optimized, a meaningful change in biomarker expression is infrequent. This study supports that when specimens are appropriately triaged, CIT of 4 hours or less may be acceptable.
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http://dx.doi.org/10.1093/ajcp/aqz105DOI Listing
November 2019

Microglandular Adenosis and Associated Invasive Carcinoma.

Arch Pathol Lab Med 2020 01 22;144(1):42-46. Epub 2019 May 22.

From the Department of Pathology, Medical College of Wisconsin, Milwaukee.

Context.—: Microglandular adenosis is a rare borderline neoplastic lesion of the breast composed of haphazardly located small, round tubules with a single cell layer interspersed within breast stroma and/or adipose tissue. Microglandular adenosis is devoid of a myoepithelial cell layer, and has a characteristic immunophenotype, being positive for S100 and negative for estrogen receptor, progesterone receptor, and HER2/. When associated with cancer, microglandular adenosis and associated invasive carcinoma share the same molecular alterations, including mutation; therefore, microglandular adenosis is considered a nonobligate precursor of triple (HER2/, estrogen and progesterone receptors)-negative breast carcinoma. Microglandular adenosis is an important diagnostic pitfall as it can be easily mistaken for a low-grade invasive carcinoma.

Objective.—: To provide a review of the clinicopathologic features of microglandular adenosis and associated invasive carcinoma, with emphasis on key features separating entities in the differential diagnosis.

Data Sources.—: Review of current literature on microglandular adenosis and associated invasive carcinoma and personal experience of authors.

Conclusions.—: Microglandular adenosis can mimic breast carcinoma; attention to key features, including morphologic-immunophenotypic correlation, is essential in establishing the diagnosis.
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http://dx.doi.org/10.5858/arpa.2019-0049-RADOI Listing
January 2020

Encapsulated and solid papillary carcinomas of the breast: Tumors in transition from in situ to invasive?

Breast J 2019 05 10;25(3):539-541. Epub 2019 Apr 10.

Pathology, Medical College of Wisconsin, Milwaukee, Wisconsin.

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http://dx.doi.org/10.1111/tbj.13278DOI Listing
May 2019

Outcomes of benign intraductal papillomas diagnosed on core biopsy: a review of 104 cases with subsequent excision from a single institution.

Virchows Arch 2018 Dec 6;473(6):679-686. Epub 2018 Sep 6.

Department of Pathology and Laboratory Medicine, University of Michigan, Ann Arbor, MI, 48109, USA.

A diagnosis of papilloma with atypia on core biopsy (CB) requires excision, as the risk of associated malignancy is high (average 36.9%). The management of benign intraductal papillomas (IP) diagnosed on CB is controversial due to varying upgradation rates (0-29%, average 7%) reported on excision. Our aim was to study the clinical, radiological, and pathological features associated with benign IP upgradation at our institution. An electronic data base search (keyword papilloma), from Jan. 2000-Aug. 2015 identified 258 CBs. After exclusions, 104 CBs of benign IPs with subsequent excisions from 101 females were reviewed. The clinical, radiological, and pathological features between IPs that had upgrades (defined as malignancy or atypical ductal hyperplasia) and non-upgraded IPs were compared using descriptive statistics. Studies of benign IP on CB with at least 50 follow-up excisions published between 2008 and 2016 were analyzed. Residual IP was present in 83.6% (87/104) of reviewed excisions. There were six upgrades (5.6%) (4 to malignancy (3.8%) and 2 to atypical ductal hyperplasia).Upgrades were associated with mass on imaging with a trend to significance (p = .05). Two cases with malignant upgrade had a history of contralateral cancer. An analysis of 25 published studies showed an average malignant upgrade of 5.7% (182/3164). The majority of benign IP are not upgraded on excision; thus, not all need to be excised. Those that may warrant excision are those with prior history of carcinoma, those with a mass on imaging, and/or suboptimal or imaging-discordant CB sampling.
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http://dx.doi.org/10.1007/s00428-018-2449-3DOI Listing
December 2018

Pleomorphic Lobular Carcinoma In Situ: Imaging Features, Upgrade Rate, and Clinical Outcomes.

AJR Am J Roentgenol 2018 08 12;211(2):462-467. Epub 2018 Jun 12.

1 Department of Radiology and Comprehensive Cancer Center, Michigan Medicine-University of Michigan, 1500 E Medical Center Dr, UH B1D502, Ann Arbor, MI 48109-5030.

Objective: Pleomorphic lobular carcinoma in situ (PLCIS) is an aggressive subtype of lobular carcinoma in situ treated similarly to ductal carcinoma in situ. The purpose of this study was to determine the imaging findings, upgrade rate of PLCIS at core needle biopsy (CNB), and the treatment and outcomes of these patients.

Materials And Methods: This retrospective single-institution study included women with PLCIS at CNB or excisional biopsy without concomitant DCIS or invasive carcinoma between January 1, 1999, and July 20, 2016. Imaging findings, detection mode, treatment, and outcomes were reviewed. Retrospective review of the images was performed. Upgrade rate to ductal carcinoma in situ or invasive carcinoma at lumpectomy was calculated.

Results: Twenty-one patients had a finding of PLCIS at CNB (n = 16) or excisional biopsy (n = 5). Four of 15 (27%; 95% CI, 4-49%) cases of PLCIS at CNB were upgraded to DCIS (two cases) or invasive lobular cancer (two cases) at lumpectomy (one patient declined excision). No unique mammographic features were predictive of need to upgrade or extent of disease. Among the patients with pure PLCIS (not upgraded), 13 of 16 (81%) presented with fine pleomorphic calcifications on screening mammograms, 1 of 16 (6%) with distortion and calcifications, 1 of 16 (6%) with a mass, and 1 of 16 (6%) with nonmass enhancement at MRI. The median imaging size was 11 mm (mean, 14 mm; range, 3-47 mm). Twelve of 16 (75%) patients were treated with lumpectomy and 4 of 16 (25%) with mastectomy. Eight of 16 (50%) patients received adjuvant hormonal therapy, and 2 of 16 (17%) received radiation. There were no local recurrences.

Conclusion: PLCIS most commonly presented as fine pleomorphic calcifications on mammograms and had a high upgrade rate after CNB. CNB diagnosis of PLCIS requires surgical excision.
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http://dx.doi.org/10.2214/AJR.17.19088DOI Listing
August 2018

Patient-friendly pathology reports for patients with breast atypias.

Breast J 2018 09 20;24(5):855-857. Epub 2018 May 20.

Department of Pathology, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA.

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http://dx.doi.org/10.1111/tbj.13061DOI Listing
September 2018

A rapid triage protocol to optimize cold ischemic time for breast resection specimens.

Ann Diagn Pathol 2018 Jun 6;34:94-97. Epub 2018 Mar 6.

Medical College of Wisconsin, Department of Pathology, 9200 W. Wisconsin Ave., Lab Bldg., Lower Level, L53, Milwaukee, WI 53226, USA. Electronic address:

Prolonged time from specimen excision to adequate formalin exposure, or cold ischemic time (CIT), negatively impacts estrogen receptor (ER), progesterone receptor (PR) and HER-2 biomarker studies routinely performed on breast specimens. Current guidelines recommend CIT of ≤1 h. Since formalin penetrates resections slowly, optimal fixation requires incision. We evaluated the efficacy of a rapid triage protocol developed to optimize CIT. We identified 2821 specimens: 650 (23.0%) excisional biopsies (EB), 1051 (37.3%) lumpectomies, and 1120 (39.7%) mastectomies. CIT was available for 2362 (83.7%), with 1845 (78.1%) ≤1 h and 2323 (98.3%) ≤4 h. IHC was performed in 533/2821 (18.9%) and was associated with lumpectomy and mastectomy procedures when compared to EB. However, IHC was also performed on 11.1% (72/650) of EB specimens despite EB being significantly less likely to have CIT recorded (468/650; 72% for EB vs. 1894/2171; 87.2% for lumpectomies/mastectomies). Our study highlights the need for rapid triage of breast resections with known or suspected malignant diagnoses and outlines our procedure for optimizing CIT. Additionally, we advocate treating ALL breast resections as having the potential of being malignant and requiring biomarker studies for which optimal CIT is of great importance.
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http://dx.doi.org/10.1016/j.anndiagpath.2018.02.010DOI Listing
June 2018

Invasive Mammary Carcinoma With Mixed Invasive Papillary and Glycogen Rich Clear Cell Features.

Int J Surg Pathol 2018 Sep 27;26(6):569-572. Epub 2018 Mar 27.

1 Medical College of Wisconsin, Milwaukee, WI, USA.

Invasive papillary carcinoma (IPC) and glycogen-rich clear cell carcinoma (GRCCC) are rare primary breast carcinomas. IPC typically have favorable prognosis, whereas the prognosis of GRCCC is less established. We report a unique case of high-grade invasive mammary carcinoma with mixed IPC and GRCCC features. We review the imaging and pathologic features and discuss prognosis of these unusual breast cancer subtypes.
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http://dx.doi.org/10.1177/1066896918765651DOI Listing
September 2018

Metastatic and hematolymphoid neoplasms involving the breast: 20-year experience at a Tertiary Center.

Breast J 2018 07 14;24(4):680-682. Epub 2018 Mar 14.

Department of Pathology, Michigan Medicine, Ann Arbor, MI, USA.

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http://dx.doi.org/10.1111/tbj.13020DOI Listing
July 2018

Primary Breast Atypical Lipomatous Tumor/ Well-Differentiated Liposarcoma and Dedifferentiated Liposarcoma.

Arch Pathol Lab Med 2018 Feb;142(2):268-274

Atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) and its higher-grade counterpart, dedifferentiated liposarcoma (DDL), are extraordinarily rare tumors in the breast. The main differential diagnostic consideration of primary breast ALT/WDL is malignant phyllodes tumor with liposarcomatous differentiation, and the main differential diagnostic consideration of DDL in the breast is metaplastic breast carcinoma, particularly the spindle cell type, with heterologous sarcomatous differentiation. These differential diagnoses may be particularly challenging when evaluating limited core needle biopsy sampling. MDM2 and/or CDK4 protein overexpression and gene amplification are beneficial ancillary studies that can help establish the diagnosis of primary breast ALT/WDL and DDL, and effectively rule out the diagnoses of malignant phyllodes tumor and metaplastic breast carcinoma.
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http://dx.doi.org/10.5858/arpa.2016-0380-RSR2DOI Listing
February 2018

Glycogen-Rich Clear Cell Carcinoma: A Rare Variant of Breast Carcinoma of Uncertain Significance.

Int J Surg Pathol 2018 09 18;26(6):530-531. Epub 2017 Dec 18.

1 Medical College of Wisconsin, Milwaukee, WI, USA.

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http://dx.doi.org/10.1177/1066896917748743DOI Listing
September 2018

Pleomorphic Lobular Carcinoma: A Controversially Aggressive Variant of Invasive Lobular Carcinoma of the Breast.

Int J Surg Pathol 2018 Aug 3;26(5):434-436. Epub 2017 Dec 3.

1 Medical College of Wisconsin, Milwaukee, WI, USA.

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http://dx.doi.org/10.1177/1066896917744878DOI Listing
August 2018

Isolated Atypical Lobular Hyperplasia Diagnosed on Breast Biopsy: Low Upgrade Rate on Subsequent Excision With Long-Term Follow-up.

Arch Pathol Lab Med 2018 Mar 21;142(3):391-395. Epub 2017 Nov 21.

From the Departments of Pathology (Drs Muller and Jorns) and Biostatistics (Ms Roberts and Dr Zhao), Michigan Medicine, Ann Arbor.

Context: - The upgrade rate to carcinoma on excision for atypical lobular hyperplasia diagnosed on breast biopsy is controversial.

Objective: - To review cases with isolated atypical lobular hyperplasia on biopsy to establish the rate of upgrade on excision and correlate with long-term follow-up.

Design: - A database search was performed for 191 months to identify breast core biopsies with isolated atypical lobular hyperplasia. Cases with other atypical lesions in the biopsy or discordant radiologic-pathologic findings were excluded. Invasive carcinoma and ductal carcinoma in situ were considered upgraded pathology on excision. Patients without and with a history of, or concurrent diagnosis of, breast carcinoma were compared.

Results: - Eighty-seven cases of isolated atypical lobular hyperplasia on biopsy underwent subsequent excision, which resulted in 3 upgraded cases (3.4%). All 3 cases with immediate upgrades revealed ductal carcinoma in situ. Upgrade was higher in patients with a concurrent diagnosis of breast carcinoma (2 of 26 and 1 of 61; 7.7% versus 1.6%, respectively). Follow-up information was available for 63 patients (57.8 ± 43.9 months; range, 6-183 months). Overall, 13% of patients without a history of breast carcinoma had a future breast cancer event, with the majority (83%) presenting in the contralateral breast.

Conclusions: - With careful radiologic-pathologic correlation, the upgrade rate for isolated atypical lobular hyperplasia on biopsy is low, and a more conservative approach may be appropriate.
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http://dx.doi.org/10.5858/arpa.2017-0155-OADOI Listing
March 2018

Localization for Breast Surgery: The Next Generation.

Arch Pathol Lab Med 2017 Oct;141(10):1324-1329

Context: - Preoperative localization of nonpalpable breast lesions using image-guided wire placement has been a standard of breast imaging, diagnosis, and treatment since its development in the 1970s. With this technique, coordinated, same-day wire placement by the radiologist and surgery are required, which can lead to significant inefficiencies in workflow. Other disadvantages of wire localization (WL) include limitations in surgical incision and dissection route and protruding wires that can be both bothersome for the patient and have risk of displacement.

Objective: - To outline several recently developed techniques that could replace traditional WL and eliminate its disadvantages. The first developed was radioactive seed localization (RSL) using I-125, a technique adopted by many institutions during the last few years. The challenge to this method, however, is the strict nuclear regulatory requirements, which can be a significant burden and limitation. The disadvantages of WL and RSL have provided incentive for the development of other types of preoperative localization procedures. Two of these are recently US Food and Drug Administration-cleared, nonradioactive, non-wire location technologies emerging as alternatives to WL and RSL; SAVI SCOUT (Cianna Medical Inc, Aliso Viejo, California), which uses infrared light and a microimpulse radar reflector, and Magseed (Endomagnetics Inc, Austin, Texas), which uses a magnetic seed for localization.

Data Sources: - We review the published literature on non-wire location technologies for breast tissue resection.

Conclusions: - Non-wire location techniques are beneficial, allowing image-guided placement before the day of surgery and resulting in improved workflows. These techniques also eliminate bothersome protruding wires, risk of dislodging, and allow the incision site to be independent from the localization site.
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http://dx.doi.org/10.5858/arpa.2017-0214-RADOI Listing
October 2017

Primary atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) of the breast.

Breast J 2018 05 27;24(3):400-401. Epub 2017 Aug 27.

Department of Pathology, University of Michigan, Ann Arbor, MI, USA.

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http://dx.doi.org/10.1111/tbj.12916DOI Listing
May 2018

Do Nonseminomatous Germ Cell Tumors of the Testis With Lymphovascular Invasion of the Spermatic Cord Merit Staging as pT3?

Am J Surg Pathol 2017 Oct;41(10):1397-1402

Departments of *Pathology †Urology ¶¶Radiology, University of Alabama at Birmingham, Birmingham, AL Departments of ‡Pathology ∥Biostatistics ‡‡Hematology/Oncology, Indiana University School of Medicine, Indianapolis, IN §Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD ¶Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA #Department of Pathology, Keck School of Medicine of University of Southern California ∥∥Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles **Department of Pathology, Stanford Medicine, Stanford, CA ††Department of Pathology, Lenox Hill Hospital, New York, NY §§Department of Pathology, University of Michigan, Ann Arbor, MI ##Department of Pathology, University of Pennsylvania, Philadelphia, PA.

The staging of testicular nonseminomatous germ cell tumors (NSGCTs) with lymphovascular invasion (LVI) of the spermatic cord in the absence of cord parenchymal involvement remains controversial. Our previous study showed that tumors with spermatic cord LVI present at a higher clinical stage than tumors with LVI confined to the testis (pT2). We compared NSGCTs with LVI of the spermatic cord without direct involvement of the spermatic cord soft tissues to pT3 tumors to help clarify the appropriate staging of this histologic finding. A retrospective, multi-institutional review was performed to identify cases of NSGCTs with LVI in the spermatic cord without soft tissue invasion of the cord. The clinical-pathologic findings were compared with NSGCTs with spermatic cord soft tissue invasion (pT3). We identified 38 pT2 NSGCTs with LVI in the spermatic cord without soft tissue invasion of the cord and 89 pT3 tumors. There were no significant differences in patient age, tumor size, or clinical stage at presentation between the 2 groups. There were no significant differences in dominant histologic subtype, rete testis invasion, hilar soft tissue invasion, or margin status. There were no significant differences in disease recurrence/progression (P=0.63), recurrence/progression after chemotherapy (P=0.35), or death (P=0.51) between patients with only spermatic cord LVI versus patients with cord soft tissue invasion. In patients with pT2 NSGCTs according to the current staging, LVI in the spermatic cord without cord soft tissue invasion is comparable with pT3 tumors in terms of clinical stage at presentation as well as disease recurrence and survival.
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http://dx.doi.org/10.1097/PAS.0000000000000917DOI Listing
October 2017

Clinicopathological findings in female-to-male gender-affirming breast surgery.

Histopathology 2017 Dec 22;71(6):859-865. Epub 2017 Sep 22.

Department of Pathology, Michigan Medicine, Ann Arbor, MI, USA.

Aims: Gender dysphoria is a diagnosis whereby an individual identifies as the opposite gender. The management of patients seeking female-to-male (FTM) transition includes hormonal therapy and surgical intervention, including mastectomy. The aim of this study was to characterize the immunohistological findings in resection specimens from FTM patients.

Methods And Results: We reviewed 68 cases (67 patients, one with re-excision) of FTM breast tissue resection by collecting clinical data, reviewing breast imaging and pathology reports (gross fibrous density, specimen weight, and number of cassettes submitted), and reviewing pathology slides [number of tissue pieces submitted, number of terminal duct lobule units (TDLUs), and the presence of histological findings]. Significant histological findings were present in 51 of 68 (75.0%) cases, including one case (1.5%) of flat epithelial atypia. Fibrocystic changes were the most common finding (27/68, 39.7%), followed by gynaecomastoid change, fibrotic stage, (22/68, 32.4%), and fibroadenomatoid change (11/68, 16.2%). Fibrocystic change was associated with increased numbers of TDLUs, and gynaecomastoid change was associated with lower body mass index and decreased numbers of TDLUs. Gynaecomastoid change showed a moderate proportion of luminal epithelial cells with strong-intensity immunohistochemical staining for oestrogen receptor, progesterone receptor, and androgen receptor, and a three-layered epithelium demonstrated by the use of cytokeratin 5/6 immunohistochemistry.

Conclusions: We identified gynaecomastoid change at a significantly higher rate than previously reported in female patients. We support the continued gross and histological evaluation of FTM specimens in light of the identification of atypia in one case.
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http://dx.doi.org/10.1111/his.13299DOI Listing
December 2017

Metaplastic Carcinoma With Extensive Chondromyxoid Differentiation Arising in Association With Microglandular Adenosis.

Int J Surg Pathol 2017 Sep 1;25(6):513-514. Epub 2017 Mar 1.

1 University of Michigan, Ann Arbor, MI, USA.

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http://dx.doi.org/10.1177/1066896917697822DOI Listing
September 2017

The Significance of Lymphovascular Invasion of the Spermatic Cord in the Absence of Cord Soft Tissue Invasion.

Arch Pathol Lab Med 2017 Jun 31;141(6):824-829. Epub 2017 Mar 31.

From the Departments of Pathology (Drs McCleskey and Gordetsky), Urology (Drs Rais-Bahrami and Gordetsky), and Radiology (Dr Rais-Bahrami), University of Alabama, Birmingham; the Department of Pathology, University of Michigan, Ann Arbor (Dr Jorns); the Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles (Dr Lu); the Department of Pathology, Brown University, Providence, Rhode Island (Dr Matoso); the Department of Pathology, University of Pennsylvania, Philadelphia (Dr Schwartz); the Departments of Hematology/Oncology (Drs Albany and Hashemi-Sadraei) and Pathology (Drs Idrees and Ulbright), Indiana University School of Medicine, Indianapolis; and the Department of Pathology, The Johns Hopkins Hospital, Baltimore, Maryland (Dr. Epstein).

Context: - Testicular germ cell tumors with lymphovascular invasion (LVI) are staged pT2, and those with spermatic cord involvement are staged pT3.

Objective: - To study the clinical significance of LVI within the spermatic cord without direct involvement of the cord soft tissues.

Design: - A retrospective, multi-institutional review was performed on testicular GCTs with spermatic cord LVI in the absence of cord soft tissue invasion.

Results: - Forty-four germ cell tumors had LVI in the spermatic cord without soft tissue invasion; 37 of 44 patients (84%) had nonseminomatous germ cell tumors (NSGCT), and 7 (16%) had pure seminomas. Patients with NSGCTs and spermatic cord LVI had worse clinical outcomes compared with patients with pure seminoma and spermatic cord LVI (P = .008). We then compared patients with NSGCTs and spermatic cord LVI (n = 37) to patients with NSGCTs and LVI limited to the testis (n = 32). A significantly greater percentage of patients with LVI in the spermatic cord presented with advanced clinical stage (76% versus 50%; P = .01). There was no statistically significant difference in disease recurrence/progression or death between patients with spermatic cord LVI and patients with LVI limited to the testis (P = .40; P = .50). There was no significant difference in the presence of embryonal dominant histology (P = .30) or rete testis invasion (P = .50) between the 2 groups. More hilar soft tissue invasion was seen in patients with LVI present in the spermatic cord (P = .004).

Conclusions: - In patients with NSGCTs, LVI in the spermatic cord, without soft tissue invasion, is associated with worse clinical stage at presentation compared with patients with LVI confined to the testis.
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http://dx.doi.org/10.5858/arpa.2016-0226-OADOI Listing
June 2017