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Article ; Online: Neoadjuvant Therapy in Breast Cancer: Histologic Changes and Clinical Implications.

Troxell, Megan L / Gupta, Tanya

Surgical pathology clinics

2022 Volume 15, Issue 1, Page(s) 57–75

Abstract: Cytotoxic or endocrine therapy before surgery (neoadjuvant) for breast cancer has become standard of care, affording the opportunity to assess and quantify response in the subsequent resection specimen. Correlation with radiology, cassette mapping, and ... ...

Abstract	Cytotoxic or endocrine therapy before surgery (neoadjuvant) for breast cancer has become standard of care, affording the opportunity to assess and quantify response in the subsequent resection specimen. Correlation with radiology, cassette mapping, and histologic review with a semi-quantitative reporting system such as residual cancer burden (RCB) provides important prognostic data that may guide further therapy. The tumor bed should be identified histologically, often as a collagenized zone devoid of normal breast epithelium, with increased vasculature. Identification of residual treated carcinoma may require careful high power examination, as residual tumor cells may be small and dyscohesive; features are widely variable and include hyperchromatic small, large, or multiple nuclei with clear, foamy, or eosinophilic cytoplasm. Calculation of RCB requires residual carcinoma span in 2 dimensions, estimated carcinoma cellularity (% area), number of involved lymph nodes, and span of largest nodal carcinoma. These RCB parameters may differ from AJCC staging measurements, which depend on only contiguous carcinoma in breast and lymph nodes.
MeSH term(s)	Antineoplastic Combined Chemotherapy Protocols ; Breast/pathology ; Breast Neoplasms/pathology ; Female ; Humans ; Neoadjuvant Therapy ; Neoplasm, Residual ; Prognosis
Language	English
Publishing date	2022-01-31
Publishing country	United States
Document type	Journal Article ; Review
ISSN	1875-9157
ISSN (online)	1875-9157
DOI	10.1016/j.path.2021.11.004
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Article: Merkel cell carcinoma, melanoma, metastatic mimics of breast cancer.

Troxell, Megan L

Seminars in diagnostic pathology

2017 Volume 34, Issue 5, Page(s) 479–495

Abstract: Merkel cell carcinoma and melanoma can each occur primarily in breast skin, or metastasize to the breast. The breast is a rare site of metastasis of essentially any and every type of tumor, including carcinomas, sarcomas, and hematolymphoid neoplasms, ... ...

Abstract	Merkel cell carcinoma and melanoma can each occur primarily in breast skin, or metastasize to the breast. The breast is a rare site of metastasis of essentially any and every type of tumor, including carcinomas, sarcomas, and hematolymphoid neoplasms, and 10-30% of breast metastases may represent the initial presentation of disease. Although metastases generally recapitulate histologic features of the primary tumor, they are diagnostically challenging given their rarity and morphologic overlap with breast carcinoma, including special types of breast cancer. Histologic clues may include lack of carcinoma in situ, lack of central elastosis, pattern of infiltration around normal breast structures, yet none of these are specific. Careful correlation with clinical history and judicious use of immunostain panels is essential in approaching these cases.
MeSH term(s)	Biopsy ; Breast Neoplasms/chemistry ; Breast Neoplasms/pathology ; Breast Neoplasms/secondary ; Carcinoma, Merkel Cell/chemistry ; Carcinoma, Merkel Cell/secondary ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; Melanoma/chemistry ; Melanoma/secondary ; Predictive Value of Tests ; Skin Neoplasms/chemistry ; Skin Neoplasms/pathology
Language	English
Publishing date	2017-09
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	605834-6
ISSN	1930-1111 ; 0740-2570
ISSN (online)	1930-1111
ISSN	0740-2570
DOI	10.1053/j.semdp.2017.05.009
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Zs.A 1988: Show issues

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Article ; Online: NELL1-Positive HIV-Associated Lupus-Like Membranous Nephropathy with Spontaneous Remission.

Dinesh, Kumar P / Charu, Vivek / Troxell, Megan L / Andeen, Nicole K

Glomerular diseases

2022 Volume 2, Issue 4, Page(s) 184–188

Abstract: Introduction: Kidney biopsy findings in patients with human immunodeficiency virus (HIV) are diverse, and optimal therapy for the various immune complex diseases in the setting of HIV is unknown.: Case presentation: A man with well-controlled HIV ... ...

Abstract	Introduction: Kidney biopsy findings in patients with human immunodeficiency virus (HIV) are diverse, and optimal therapy for the various immune complex diseases in the setting of HIV is unknown. Case presentation: A man with well-controlled HIV developed nephrotic range proteinuria, and kidney biopsy revealed lupus-like glomerulonephritis with a predominantly membranous pattern of injury. He opted for conservative therapy and experienced spontaneous and sustained remission. Subsequent testing revealed neural epidermal growth factor-like 1 (NELL1)-positive glomerular immune deposits. NELL1-positive glomerular immune deposits were identified in a total of 2 of 5 tested HIV-associated membranous nephropathy (MN), which were morphologically dissimilar and one of which weakly co-expressed phospholipase A2 receptor (PLA2R). Discussion: This case suggests potentially different outcomes in patients with immune complex diseases in the setting of HIV based on disease etiology and histopathology. HIV-associated MN is occasionally NELL1-positive.
Language	English
Publishing date	2022-06-29
Publishing country	Switzerland
Document type	Case Reports
ISSN	2673-3633
ISSN (online)	2673-3633
DOI	10.1159/000525541
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Article ; Online: Systemic Lupus Erythematosus and ANCA-Associated Vasculitis Overlap Syndrome: A Case Report.

Khil, Jaclyn / Nguyen, Thuy M / Troxell, Megan L / Zheng, Sijie

Kidney medicine

2022 Volume 4, Issue 11, Page(s) 100544

Abstract: Concomitant lupus nephritis and antineutrophil cytoplasmic antibody-positive crescentic glomerulonephritis is rare, and there is little guidance on the management and outcomes of these patients. A Hispanic woman in her early 40s with no contributory ... ...

Abstract	Concomitant lupus nephritis and antineutrophil cytoplasmic antibody-positive crescentic glomerulonephritis is rare, and there is little guidance on the management and outcomes of these patients. A Hispanic woman in her early 40s with no contributory medical history presented with 3 weeks of cough, shortness of breath, fever, and malaise. Laboratory test results were notable for serum creatinine level of 17.4 mg/dL (previously normal), urinalysis with a high hemoglobin level, >182 red blood cell count, and urinary protein-creatinine ratio of 5.72 g/g. Serologies showed elevated dsDNA, ribonucleoprotein antibody, Smith antibody, myeloperoxidase antibody, positive antinuclear antibody, and low complement levels. She was urgently started on hemodialysis and solumedrol 1 g for 3 days. On day 2, she had a kidney biopsy, which showed necrotizing crescentic glomerulonephritis and immunofluorescence with "full house" pattern, immune complex deposits, and strong antinuclear antibody staining of nuclei. She developed diffuse alveolar hemorrhage and was initiated on plasmapheresis and cyclophosphamide. She improved and was discharged without needing further dialysis. Clinicians should consider systemic lupus erythematosus and antineutrophil cytoplasmic antibody disease overlap syndrome when a young, female patient presents with new kidney failure and alveolar hemorrhage. Early biopsy and aggressive treatment are essential in preserving kidney function, and plasmapheresis should be considered in severe cases. This is a severe case with a positive outcome.
Language	English
Publishing date	2022-09-16
Publishing country	United States
Document type	Case Reports
ISSN	2590-0595
ISSN (online)	2590-0595
DOI	10.1016/j.xkme.2022.100544
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Article ; Online: Reversed MUC1/EMA polarity in both mucinous and micropapillary breast carcinoma.

Troxell, Megan L

Human pathology

2014 Volume 45, Issue 2, Page(s) 432–434

MeSH term(s)	Adenocarcinoma, Mucinous/pathology ; Breast Neoplasms/pathology ; Carcinoma, Papillary/pathology ; Female ; Humans
Language	English
Publishing date	2014-02
Publishing country	United States
Document type	Comment ; Letter
ZDB-ID	207657-3
ISSN	1532-8392 ; 0046-8177
ISSN (online)	1532-8392
ISSN	0046-8177
DOI	10.1016/j.humpath.2013.08.026
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Zs.A 722: Show issues

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Article ; Online: Digital Image Analysis and Quantitative Bead Standards in Root Cause Analysis of Immunohistochemical Staining Variability: A Real-world Example.

Rojansky, Rebecca / Sompuram, Seshi R / Gomulia, Ellen / Natkunam, Yasodha / Troxell, Megan L / Fernandez-Pol, Sebastian

Applied immunohistochemistry & molecular morphology : AIMM

2022 Volume 30, Issue 7, Page(s) 477–485

Abstract: Assessment of automated immunohistochemical staining platform performance is largely limited to the visual evaluation of individual slides by trained personnel. Quantitative assessment of stain intensity is not typically performed. Here we describe our ... ...

Abstract	Assessment of automated immunohistochemical staining platform performance is largely limited to the visual evaluation of individual slides by trained personnel. Quantitative assessment of stain intensity is not typically performed. Here we describe our experience with 2 quantitative strategies that were instrumental in root cause investigations performed to identify the sources of suboptimal staining quality (decreased stain intensity and increased variability). In addition, these tools were utilized as adjuncts in validation of a new immunohistochemical staining instrument. The novel methods utilized in the investigation include quantitative assessment of whole slide images (WSI) and commercially available quantitative calibrators. Over the course of ~13 months, these methods helped to identify and verify correction of 2 sources of suboptimal staining. One root cause of suboptimal staining was insufficient/variable power delivery from our building's electrical circuit. This led us to use uninterruptible power managers for all automated immunostainer instruments, which restored expected stain intensity and consistency. Later, we encountered one instrument that, despite passing all vendor quality control checks and not showing error alerts was suspected of yielding suboptimal stain quality. WSI analysis and quantitative calibrators provided a clear evidence that proved critical in confirming the pathologists' visual impressions. This led to the replacement of the instrument, which was then validated using a combination of standard validation metrics supplemented by WSI analysis and quantitative calibrators. These root cause analyses document 2 variables that are critical in producing optimal immunohistochemical stain results and also provide real-world examples of how the application of quantitative tools to measure automated immunohistochemical stain output can provide a greater objectivity when assessing immunohistochemical stain quality.
MeSH term(s)	Coloring Agents ; Diagnostic Imaging/methods ; Humans ; Image Processing, Computer-Assisted/methods ; Quality Control ; Root Cause Analysis ; Staining and Labeling
Chemical Substances	Coloring Agents
Language	English
Publishing date	2022-07-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	1473273-7
ISSN	1533-4058 ; 1062-3345 ; 1541-2016
ISSN (online)	1533-4058
ISSN	1062-3345 ; 1541-2016
DOI	10.1097/PAI.0000000000001045
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Zs.A 3783: Show issues

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Article ; Online: Clinicopathologic features of non-lupus membranous nephropathy in a pediatric population.

Miller, Paul / Lei, Li / Charu, Vivek / Higgins, John / Troxell, Megan / Kambham, Neeraja

Pediatric nephrology (Berlin, Germany)

2022 Volume 37, Issue 12, Page(s) 3127–3137

Abstract: Background: Membranous nephropathy is an uncommon cause of nephrotic syndrome in pediatrics.: Methods: We reviewed our kidney biopsy records for patients ≤ 20 years of age with membranous nephropathy without evidence of systemic lupus erythematosus ... ...

Abstract	Background: Membranous nephropathy is an uncommon cause of nephrotic syndrome in pediatrics. Methods: We reviewed our kidney biopsy records for patients ≤ 20 years of age with membranous nephropathy without evidence of systemic lupus erythematosus within 6 months of biopsy (January 1995-September 2020). Staining for PLA2R, NELL1, THSD7A, SEMA3B, EXT2 (3 biopsies), and IgG-subclass were performed. Results: Sixteen children (≤ 12 years) and 25 adolescents (13-20 years) were identified. Four children and 15 adolescents showed autoantigen positivity: PLA2R+/SEMA3B- (13), SEMA3B+/PLA2R+ (2), SEMA3B+/PLA2R- (1), NELL1 (1), EXT2+ (2), and THSD7A (0). Co-morbidities associated with PLA2R positivity included IPEX syndrome, active hepatitis B, Von Hippel Lindau syndrome, solitary kidney, type 1 diabetes, hyperuricemia, pregnancy (1), obesity (3), type II diabetes, H. pylori, viral prodrome, and nephrolithiasis. The SEMA3B+/PLA2R- adolescent was pregnant, the NELL1+ adolescent was obese, and the two EXT2+ adolescents eventually met the clinical criteria for lupus (4, 9 years post-biopsy). Co-morbidities among the remaining 24 patients included remote hepatitis B (2), Down's syndrome, lysinuric protein intolerance, recurrent UTIs, hypothyroidism, pregnancy (3), and obesity (2). Follow-up data was available for 12 children and 16 adolescents. Of the 12 children, 6 achieved complete remission, 4 achieved partial remission, and 2 had no response to treatment (1 transplant). Of the 16 adolescents, 4 achieved complete remission, 4 achieved partial remission, and 8 had no response to treatment (3 transplants). A child with "full-house" immunofluorescence staining achieved spontaneous disease remission. Conclusion: Our non-lupus membranous nephropathy cohort represents one of the largest pediatric studies to date. A higher resolution version of the Graphical abstract is available as Supplementary information.
MeSH term(s)	Adolescent ; Child ; Humans ; Autoantibodies ; Autoantigens ; Diabetes Mellitus, Type 2 ; Glomerulonephritis, Membranous/pathology ; Hepatitis B ; Immunoglobulin G ; Obesity ; Receptors, Phospholipase A2/metabolism ; Young Adult
Chemical Substances	Autoantibodies ; Autoantigens ; Immunoglobulin G ; Receptors, Phospholipase A2
Language	English
Publishing date	2022-03-25
Publishing country	Germany
Document type	Review ; Journal Article
ZDB-ID	631932-4
ISSN	1432-198X ; 0931-041X
ISSN (online)	1432-198X
ISSN	0931-041X
DOI	10.1007/s00467-022-05503-7
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Zs.A 2196: Show issues

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Article ; Online: Polyacrylamide-based hydrogel coatings improve biocompatibility of implanted pump devices.

Chan, Doreen / Maikawa, Caitlin L / d'Aquino, Andrea I / Raghavan, Shyam S / Troxell, Megan L / Appel, Eric A

Journal of biomedical materials research. Part A

2023 Volume 111, Issue 7, Page(s) 910–920

Abstract: The introduction of transcutaneous and subcutaneous implants and devices into the human body instigates fouling and foreign body responses (FBRs) that limit their functional lifetimes. Polymer coatings are a promising solution to improve the ... ...

Abstract	The introduction of transcutaneous and subcutaneous implants and devices into the human body instigates fouling and foreign body responses (FBRs) that limit their functional lifetimes. Polymer coatings are a promising solution to improve the biocompatibility of such implants, with potential to enhance in vivo device performance and prolong device lifetime. Here we sought to develop novel materials for use as coatings on subcutaneously implanted devices to reduce the FBR and local tissue inflammation in comparison to gold standard materials such as poly(ethylene glycol) and polyzwitterions. We prepared a library of polyacrylamide-based copolymer hydrogels, which were selected from materials previously shown to exhibit remarkable antifouling properties with blood and plasma, and implanted them into the subcutaneous space of mice to evaluate their biocompatibility over the course of 1 month. The top performing polyacrylamide-based copolymer hydrogel material, comprising a 50:50 mixture of N-(2-hydroxyethyl)acrylamide (HEAm) and N-(3-methoxypropyl)acrylamide (MPAm), exhibited significantly better biocompatibility and lower tissue inflammation than gold standard materials. Moreover, when applied to polydimethylsiloxane disks or silicon catheters as a thin coating (45 ± 1 μm), this leading copolymer hydrogel coating significantly improved implant biocompatibility. Using a rat model of insulin-deficient diabetes, we showed that insulin pumps fitted with HEAm-co-MPAm hydrogel-coated insulin infusion catheters exhibited improved biocompatibility and extended functional lifetime over pumps fitted with industry standard catheters. These polyacrylamide-based copolymer hydrogel coatings have the potential to improve device function and lifetime, thereby reducing the burden of disease management for people regularly using implanted devices.
MeSH term(s)	Rats ; Mice ; Humans ; Animals ; Inflammation ; Polymers ; Hydrogels ; Acrylamides ; Insulins
Chemical Substances	polyacrylamide (9003-05-8) ; Polymers ; Hydrogels ; Acrylamides ; Insulins
Language	English
Publishing date	2023-03-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2099989-6
ISSN	1552-4965 ; 1549-3296 ; 0021-9304
ISSN (online)	1552-4965
ISSN	1549-3296 ; 0021-9304
DOI	10.1002/jbm.a.37521
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Article ; Online: Practical Applications in Immunohistochemistry: Evaluation of Rejection and Infection in Organ Transplantation.

Troxell, Megan L / Lanciault, Christian

Archives of pathology & laboratory medicine

2016 Volume 140, Issue 9, Page(s) 910–925

Abstract: Context: -Immunohistochemical analysis of tissue biopsy specimens is a crucial tool in diagnosis of both rejection and infection in patients with solid organ transplants. In the past 15 years, the concept of antibody-mediated rejection has been refined, ...

Abstract	Context: -Immunohistochemical analysis of tissue biopsy specimens is a crucial tool in diagnosis of both rejection and infection in patients with solid organ transplants. In the past 15 years, the concept of antibody-mediated rejection has been refined, and diagnostic criteria have been codified in renal, heart, pancreas, and lung allografts (with studies ongoing in liver, small intestine, and composite grafts), all of which include immunoanalysis for the complement split product C4d. Objectives: -To review the general concepts of C4d biology and immunoanalysis, followed by organ-allograft-specific data, and interpretative nuances for kidney, pancreas, and heart, with discussion of early literature for lung and liver biopsies. Additionally, practical applications and limitations of immunostains for infectious organisms (Polyomavirus, Adenoviridae [adenovirus], and the herpes virus family, including Herpes simplex virus, Cytomegalovirus, Human herpes virus 8, and Epstein-Barr virus) are reviewed in the context of transplant recipients. Data sources: -Our experience and published primary and review literature. Conclusions: -Immunohistochemistry continues to have an important role in transplant pathology, most notably C4d staining in assessment of antibody-mediated rejection and assessment of viral pathogens in tissue. In all facets of transplant pathology, correlation of morphology with special studies and clinical data is critical, as is close communication with the transplant team.
MeSH term(s)	Allografts/immunology ; Complement C4b/immunology ; Graft Rejection/etiology ; Graft Rejection/immunology ; Graft Rejection/virology ; Humans ; Immunohistochemistry/methods ; Organ Transplantation/adverse effects ; Organ Transplantation/methods ; Pathology, Clinical/methods ; Peptide Fragments/immunology ; Reproducibility of Results ; Virus Diseases/complications ; Virus Diseases/immunology ; Virus Diseases/virology ; Viruses/immunology
Chemical Substances	Peptide Fragments ; Complement C4b (80295-50-7) ; complement C4d (80295-52-9)
Language	English
Publishing date	2016-09
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	194119-7
ISSN	1543-2165 ; 0363-0153 ; 0096-8528 ; 0003-9985
ISSN (online)	1543-2165
ISSN	0363-0153 ; 0096-8528 ; 0003-9985
DOI	10.5858/arpa.2015-0275-CP
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Article ; Online: Allograft pancreas: pale acinar nodules.

Troxell, Megan L / Drachenberg, Cinthia

Human pathology

2016 Volume 54, Page(s) 127–133

Abstract: Microscopic pale-staining acinar nodules were characterized in native pancreas in the 1980s under a variety of names but have been infrequently reported since. We retrospectively studied the frequency and characteristics of pale acinar nodules in ... ...

Abstract	Microscopic pale-staining acinar nodules were characterized in native pancreas in the 1980s under a variety of names but have been infrequently reported since. We retrospectively studied the frequency and characteristics of pale acinar nodules in allograft pancreas biopsies, as compared to a sampling of native pancreas specimens at our center. Pale acinar nodules were present in 13% (9/69) of allograft biopsies from 22% (7/32) of transplant patients, and 23% (5/22) of native pancreas surgical specimens, although more nodules per pancreas area were present in allograft needle biopsies. Acinar nodules had size of 100 to 700 μm, were periodic acid-Schiff pale, were synaptophysin negative, stained more weakly with keratin CAM 5.2 compared to surrounding parenchyma, and had a low proliferative rate. Ultrastructural evaluation revealed paucity of zymogen granules with dilated cistern-like structures. In our experience, pale acinar nodules have similar features in allograft and native pancreas specimens, yet remain of uncertain etiology and significance.
MeSH term(s)	Acinar Cells/chemistry ; Acinar Cells/transplantation ; Acinar Cells/ultrastructure ; Allografts ; Biomarkers/analysis ; Biopsy, Needle ; Humans ; Immunohistochemistry ; Keratins/analysis ; Ki-67 Antigen/analysis ; Microscopy, Electron, Transmission ; Pancreas Transplantation/adverse effects ; Pancreas, Exocrine/chemistry ; Pancreas, Exocrine/surgery ; Pancreas, Exocrine/ultrastructure ; Retrospective Studies ; Synaptophysin/analysis ; Treatment Outcome
Chemical Substances	Biomarkers ; CAM 5.2 antigen ; Ki-67 Antigen ; Synaptophysin ; Keratins (68238-35-7)
Language	English
Publishing date	2016-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	207657-3
ISSN	1532-8392 ; 0046-8177
ISSN (online)	1532-8392
ISSN	0046-8177
DOI	10.1016/j.humpath.2016.02.029
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