Not all false positive diagnoses are equal: On the prognostic implications of false-positive diagnoses made in breast MRI versus in mammography / digital tomosynthesis screening

3 Background: The current ACR practice guidelines discourage use of MRI for work-up of suspicious findings in mammography (Mx) and ultrasound (US). We investigated whether additional breast MRI assessment of suspicious Mx and U.S. findings could improve PPV and thus possibly help reduce the number of biopsies for false positive findings in Mx or U.S. Methods: Between 06/2010 and 04/2012, a total 2,754 patients underwent DCE breast MRI. Of these, 277 underwent MRI for further work-up of suspicious findings made in Mx (n=173, 57 patients with mass lesions, 33 with asymmetries, 12 with architectural distortions, and 71 with suspicious calcifications) or U.S. (n=104, 74 with masses, 30 with miscellaneous U.S. findings such as suspected intraductal pathology, focal acoustic shadowing or architectural distortions) . All lesions categorized as MR-BIRADS 4 and 5 underwent biopsy, lesions categorized as MR-BIRADS 1 or 2 did not proceed to biopsy, except for selected women with mammographic calcifications suggestive of DCIS. Lesions categorized as MR-BIRADS 3 underwent additional short term follow-up by MRI, US and/or Mx. All women who did not undergo biopsy (MR-BIRADS 1-3) underwent long term follow-up for so far 12-24 months. Results: For suspicious lesions in mammography, MRI increased PPV from 19.3% (11/57) to 92.3% (12/13) for masses, from 3% (1/33) to 33.3% (1/3) for asymmetries, from 8.3% (1/12) to 25% (1/4) for architectural distortions and from 21.1% (15/71) to 62.5% (15/24) for calcifications. For suspicious lesions in ultrasound, MRI increased PPV from 13.5% (10/74) to 71.4% (10/14) for masses and from 3.3% (1/30) to 50% (1/2) for non-mass U.S. findings. In 4/277 patients, MRI showed additional suspicious findings, requiring MR-guided biopsy, one of which was histologically proven malignant. So far, none of the patients who, because of an MR-BIRADS 1-3, did not undergo biopsy has been diagnosed with invasive cancer or DCIS or with progressive conventional imaging findings necessitating secondary biopsy. Conclusions: MRI improves PPV for both suspicious Mx and U.S. findings, especially mass lesions. In experienced hands, careful use of MRI can help avoid biopsies for false positive diagnoses made in Mx and U.S.

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Myeloproliferative neoplasms: from origins to outcomes

Hematology ◽

10.1182/asheducation-2017.1.470 ◽

2017 ◽

Vol 2017 (1) ◽

pp. 470-479 ◽

Cited By ~ 4

Author(s):

Jyoti Nangalia ◽

Anthony R. Green

Keyword(s):

Somatic Mutations ◽

Myeloproliferative Neoplasms ◽

Myeloproliferative Neoplasm ◽

Genomic Profiling ◽

Jak Inhibitors ◽

Major Goal ◽

Disease Biology ◽

Substantial Progress ◽

Prognostic Implications ◽

Made In

Abstract Substantial progress has been made in our understanding of the pathogenetic basis of myeloproliferative neoplasms. The discovery of mutations in JAK2 over a decade ago heralded a new age for patient care as a consequence of improved diagnosis and the development of therapeutic JAK inhibitors. The more recent identification of mutations in calreticulin brought with it a sense of completeness, with most patients with myeloproliferative neoplasm now having a biological basis for their excessive myeloproliferation. We are also beginning to understand the processes that lead to acquisition of somatic mutations and the factors that influence subsequent clonal expansion and emergence of disease. Extended genomic profiling has established a multitude of additional acquired mutations, particularly prevalent in myelofibrosis, where their presence carries prognostic implications. A major goal is to integrate genetic, clinical, and laboratory features to identify patients who share disease biology and clinical outcome, such that therapies, both existing and novel, can be better targeted.

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Comparison of false positive rates for screening breast MRI in high risk women when studies are done stacked versus alternating.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.1512 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 1512-1512

Author(s):

Edress Othman ◽

Jue Wang ◽

Brian Sprague ◽

Yongli Ji ◽

Sally D. Herschorn ◽

...

Keyword(s):

Breast Cancer ◽

High Risk ◽

False Positive ◽

Brca Mutation ◽

False Positive Rate ◽

Menopausal Status ◽

Breast Mri ◽

High Risk Women ◽

Increased Risk ◽

Optimal Screening

1512 Background: Screening breast MRI added to mammography increases screening sensitivity for high risk women. However, false positive rates are high for MRI and the optimal screening schedule is unclear. In this study we compare rates of false positive MRI when studies were performed on a stacked or alternating schedule. Methods: We reviewed charts for women at increased risk for breast cancer who had screening breast MRI between 2004 - 2012 at the University of Vermont. Eligible women had at least 1 MRI and 1 mammogram performed within one year. Charts were abstracted for clinical, radiological, and biopsy data. Screening was considered stacked if both studies were performed within 90 days and alternating if studies were 4-8 months apart. False positive was defined as MRI result of BI-RADS 3-4-5-0 with additional negative imaging within 12 months or benign biopsy. Results: 143 women had screening which met inclusion criteria; 45 per stacked schedule, 52 alternating, 40 mixed and 6 neither. Women in this study had similar characteristics with respect to age, ethnicity, menopausal status and indications for MRI (i.e. family history, BRCA mutation, biopsy history and prior chest irradiation). 371 MRIs were reviewed (165 stacked and 206 alternating). The overall false positive rate was higher in the stacked group vs. alternating [30(18.2%) vs. 21(10.2%), p=0.0264]. Using only BI-RADS 4-5-0 as a positive result that difference was lost. There were significantly more BI-RADS category 3 interpretations in the stacked vs. alternating MRIs [16(9.7%) vs. 6(2.9%), p=0.006]. The rate of BI-RADS category 4-5-0 was not different between the two groups [16(9.7%) vs. 17(8.3%), p= 0.6272]. A similar number of biopsies were performed in both groups Conclusions: MRI added to mammography for women at increased risk for breast cancer was associated with higher rates of false positive interpretations when studies were done on a stacked compared to alternating schedule. In this study the greater number of BI-RADS 3 interpretations with a stacked schedule accounted for this difference. Further studies are needed to identify the optimal screening schedule when adding MRI to mammography.

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A false positive for clozapine using high-pressure liquid chromatography with ultraviolet detection

Acta Neuropsychiatrica ◽

10.1111/j.1601-5215.2012.00637.x ◽

2012 ◽

Vol 24 (4) ◽

pp. 245-246 ◽

Cited By ~ 2

Author(s):

Unax Lertxundi ◽

Margarita H. Manrique ◽

Saioa D. Echaburu ◽

Manuel Martinez

Keyword(s):

High Pressure ◽

Liquid Chromatography ◽

High Pressure Liquid Chromatography ◽

False Positive ◽

Detection Method ◽

Serum Levels ◽

Specific Method ◽

Ultraviolet Detection ◽

Test Request ◽

Made In

Background:We report a case of a false positive for clozapine, when analysing serum levels using a high-pressure liquid chromatography with ultraviolet (HPLC-UV) detection method.Methods:A patient not taking clozapine tested positive for clozapine three times in two different samples. This false positive was discovered by chance, because of an administrative error made in the first analytic test request.Results:The analysis of the first sample with a more specific method [HPLC-tandem mass spectrometry (LC-MS/MS)] showed that no clozapine was present.Conclusions:It is important to acknowledge that depending on the method employed, a false positive should not be ruled out as a possibility. Moreover, and even more worryingly, it should also be taken into account that clozapine serum levels could be tested erroneously high if the unknown interference is present and the HPLC-UV method is used. Although the interfering compound could not be identified, the possibility of a cross-reaction when analysing serum clozapine levels with the HPLC-UV method warrants urgent attention.

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Breast Magnetic Resonance Imaging of Multicentric, Multifocal and Bilateral Cancer — A Case-based Review

European Oncology & Haematology ◽

10.17925/eoh.2011.07.01.24 ◽

2011 ◽

Vol 07 (01) ◽

pp. 24

Author(s):

Virginia Pérez Dueñas ◽

María Ruíz de Gopegui Andreu ◽

Sara Morón Hodge ◽

Asunción Suárez Manrique ◽

◽

...

Keyword(s):

Breast Cancer ◽

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

False Positive ◽

Breast Magnetic Resonance Imaging ◽

Breast Mri ◽

Resonance Imaging ◽

Mri Findings ◽

Mri Features ◽

Breast Magnetic Resonance

Multifocal or multicentric breast cancer can be difficult to detect on mammography or ultrasound, particularly in patients with dense breast tissue. A multimodality approach that includes breast magnetic resonance imaging (MRI) is indicated, particularly when conservative surgery is being considered as it is the most sensitive technique for identifying additional sites of disease. However, its influence on recurrence and survival rates has yet not been clearly established, and false-positive cases may lead to more aggressive management and treatment. Radiologists should therefore be aware of relevant breast MRI findings. Infiltrating carcinomas, contralateral unsuspected carcinomas, occult carcinomas, false-positive cases and post-chemotherapy changes. Several cases of multiple-site breast carcinomas and their corresponding mammographic, ultrasound and MRI features have been reviewed for this article, in which the definition and differences between multifocal, multicentric and contralateral breast carcinoma are explained and the most relevant imaging findings on MRI are illustrated and correlated with mammogram and ultrasound findings. Finally, the role of breast MRI in the pre-operative assessment of breast cancer is discussed.

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The Genomics of Myelodysplastic Syndromes: Origins of Disease Evolution, Biological Pathways, and Prognostic Implications

Cells ◽

10.3390/cells9112512 ◽

2020 ◽

Vol 9 (11) ◽

pp. 2512

Author(s):

Hassan Awada ◽

Bicky Thapa ◽

Valeria Visconte

Keyword(s):

Experimental Studies ◽

Gene Mutations ◽

High Rate ◽

Murine Models ◽

Disease Evolution ◽

Molecular Alterations ◽

Disease Phenotypes ◽

Prognostic Implications ◽

Made In

The molecular pathogenesis of myelodysplastic syndrome (MDS) is complex due to the high rate of genomic heterogeneity. Significant advances have been made in the last decade which elucidated the landscape of molecular alterations (cytogenetic abnormalities, gene mutations) in MDS. Seminal experimental studies have clarified the role of diverse gene mutations in the context of disease phenotypes, but the lack of faithful murine models and/or cell lines spontaneously carrying certain gene mutations have hampered the knowledge on how and why specific pathways are associated with MDS pathogenesis. Here, we summarize the genomics of MDS and provide an overview on the deregulation of pathways and the latest molecular targeted therapeutics.

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Efficacy of breast MRI in elderly women

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.608 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 608-608

Author(s):

J. Yu ◽

E. Morris ◽

A. Park ◽

H. Cody ◽

M. L. Gemignani

Keyword(s):

Breast Cancer ◽

False Positive ◽

Elderly Women ◽

False Positive Rate ◽

Breast Mri ◽

Disease Assessment ◽

Mri Findings ◽

History Of ◽

Diagnosis Of Cancer ◽

Extent Of Disease

608 Background: Breast MRI is useful in evaluating extent of disease and screening of high risk patients, especially younger patients with dense breasts. The utility of MRI in the elderly population is currently unknown. The purpose of this study was to review the use of breast MRI and MRI findings in elderly women. Methods: Retrospective review identified women over the age of 70 who underwent breast MRI at our institution between 11/2000 and 12/2005. Clinicopathologic features, MRI results and mammograms (MMG) were reviewed. Results: 228 patients were identified. The mean age was 73.5 years (range 70–91). Forty-three patients (19%) had no history of breast cancer, 99 (43%) had a history of breast cancer, and 86 (38%) had a current diagnosis of breast cancer at the time of MRI. Ninety-two patients (40%) underwent MRI for screening, 49 (21%) as further workup for an abnormal MMG or physical finding, and 78 (34%) for extent of disease assessment. MRI found 49 additional sites of abnormality and 15 additional cancers (14% false positive). Five cancers were detected in women with no current diagnosis of cancer. In patients with a diagnosis of cancer at the time of MRI, 10 additional cancers were found: 7 in the contralateral breast and 3 additional ipsilateral sites. Conclusions: MRI detected an additional 15 mammographically occult breast cancers in this population of women over the age of 70. MRI was efficacious in screening as well as evaluating extent of disease, with a relatively low false-positive rate of 14%. Breast MRI is a useful tool in the evaluation of elderly patients; further study in the use of MRI for screening in this population is needed. [Table: see text] No significant financial relationships to disclose.

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Time-related changes in yield and harms of screening breast MRI.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.1508 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 1508-1508

Author(s):

Holly Jane Pederson ◽

Colin O'Rourke ◽

Lauren D Bolden ◽

Sobia Khan ◽

Manisha Yadav ◽

...

Keyword(s):

High Risk ◽

False Positive ◽

Short Interval ◽

Breast Mri ◽

Patient Characteristics ◽

Screening Mammography ◽

Significance Level ◽

High Risk Patients ◽

Risk Patients ◽

Over Time

1508 Background: MRI has been accepted as a useful adjunct to screening mammography in high-risk women. Concerns remain over false positive findings, however, and little is known about harms and yield over time. Such information will help women decide about enhanced surveillance. Methods: Of 350 high risk patients offered MRI screening, 320 underwent 757 screens with a 1.5 Tesla magnet from 2008 to 2012 alternating (q 6 mo.) with digital mammography. Data collected included patient characteristics, mammographic density, estimated lifetime risk, and need for additional imaging and/or biopsy. Harms were defined as second look ultrasounds, US or MRI guided core biopsies, surgical biopsies or recommendation for short interval follow up. Estimates of harms over time were modeled by logistic regression. A significance level of 0.05 was used for all testing. Results: Compliance with MRI screening as recommended was 91% with the first MRI, and was not associated with age, race or level of risk. Harms were highest with the first MRI and decreased significantly with subsequent MRIs. Of 59 biopsies, 7 were malignant. Two were found in MRI 1, 3 in MRI 3 and 2 in MRI 4. Women with biopsies resulting from false positive findings were significantly younger (median age 44.5 as compared with 48; p=0.049) and were more likely to have extremely dense breast tissue (36% vs 17%; p=0.028.) Conclusions: This study of highly compliant high risk patients supports the use of MRI as an adjunct to mammography for early detection. The rate of harmful events decreased over time, yet cancer detection did not. This information is critical in counseling women who are considering annual screening breast MRI, particularly younger women and those with dense tissue. [Table: see text]

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The doubtful value of tympanometry in the diagnosis of otosclerosis

The Journal of Laryngology & Otology ◽

10.1017/s002221510009722x ◽

1985 ◽

Vol 99 (6) ◽

pp. 545-547 ◽

Cited By ~ 14

Author(s):

G. G. Browning ◽

I. R. C. Swan ◽

S. Gatehouse

Keyword(s):

False Positive ◽

False Negative ◽

Positive Diagnosis ◽

False Positive Diagnosis ◽

Practical Usefulness ◽

The Mean ◽

Mean Compliance ◽

Range Of Values ◽

Normal Controls ◽

Made In

AbstractMany consider that the compliance of the middle ear as measured from the tympanogram can be helpful in diagnosing otosclerosis. To test this assertion, the compliance in 34 individuals with surgically proven otosclerosis was compared with the compliance in 34 age and sex matched, normal controls, randomly selected from the population. Though the mean compliance was different in the two groups, there was considerable overlap in the range of values which severely limits the practical usefulness of tympanometry.If the level of compliance is taken at which a false negative diagnosis would be made in 10 per cent of otosclerotic ears, a false positive diagnosis of otosclerosis would be made in 88 per cent of normal ears. If the level of compliance is taken at which a false positive diagnosis of otosclerosis would be made in 10 per cent of normal ears, 72 per cent of ears with otosclerosis would be considered normal.It is concluded that tympanometry will not help to arrive at a diagnosis of otosclerosis.

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Diagnostic Value of Ultrasonography in Hydatid Disease in Abdomen and Chest

Acta Radiologica ◽

10.1177/028418518702800618 ◽

1987 ◽

Vol 28 (6) ◽

pp. 743-745 ◽

Cited By ~ 3

Author(s):

C. S. Pant ◽

R. K. Gupta

Keyword(s):

Hydatid Cyst ◽

Hydatid Disease ◽

False Positive ◽

Diagnostic Value ◽

Diagnostic Problems ◽

Lost To Follow Up ◽

Made In

A prospective diagnosis of hydatid cyst was made in 90 cases involving abdomen and chest. It was based on the various sonographic signs of hydatid disease described in the literature. Surgery was performed in 60 patients while 30 were lost to follow-up. The diagnosis was confirmed in 55 patients while it was false positive in 5. The liver was the most common organ involved, followed by chest, kidney, peritoneum, spleen and retroperitoneum. Separation of the membrane from the wall, multiple daughter cysts, and collapsed cysts, were found to be diagnostic of hydatid disease. It is stressed that certain signs are specific for hydatid disease and thus do not cause any differential diagnostic problems.

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