Primary and Secondary Breast Lymphoma: Clinical, Pathologic, and Multimodality Imaging Review.

Breast lymphoma is a rare hematologic neoplasm that originates in the breast lymphoid tissue and includes primary breast lymphoma (PBL) and secondary breast lymphoma (SBL). PBL involves the breast lymphoid tissue in the absence of previously identified extramammary lymphoma and widespread disease. SBL is the most common metastasis to the breast, accounting for 17% of metastatic disease to the breast. PBL and SBL usually demonstrate imaging phenotypes that overlap with those of primary breast carcinoma, which makes a prospective diagnosis of breast lymphoma challenging. These nonspecific imaging features include an iso- to hyperdense oval mass or masses at mammography, a hypoechoic or mixed-echogenicity hypervascular mass at US, an enhancing mass with type II kinetics at MRI, and high fluorine 18-fluorodeoxyglucose avidity at PET. In cases of suspected lymphoma, reviewing the clinical history, using appropriate biopsy techniques, and evaluating for multiplicity, bilaterality, and distant disease are critical for diagnosis and management. A patient with PBL generally has an earlier clinical presentation with a palpable abnormality and a solitary imaging finding. In contrast, multiple masses in an older patient and an occult clinical presentation favor an SBL diagnosis. ©RSNA, 2019.

MRI-guided needle localization: Indications, tips, tricks, and review of the literature.

We describe the history of, indications for, and techniques involved in MRI-guided needle localization (MRI-NL). MRI-NL continues to be a safe, effective method of sampling lesions that are only detected with MRI, particularly for anatomically challenging lesions such as those near the chest wall, the nipple, the skin, and/or in close proximity to implants.

Comparative Dose of Contrast-Enhanced Spectral Mammography (CESM), Digital Mammography, and Digital Breast Tomosynthesis.

OBJECTIVE: The purpose of this study is to provide a more accurate estimation of the radiation dose of contrast-enhanced spectral mammography (CESM) relative to that of 2D digital mammography and tomosynthesis using phantom and patient data and an accepted dosimetry protocol that eliminates vendor-specific average glandular dose (AGD) estimates while including breast density. MATERIALS AND METHODS: Patient and phantom AGD estimation was performed using two vendors (system 1 and system 2) in five imaging modes, including 2D, 3D, and CESM imaging. Patient AGD was retrospectively estimated from 45 patients who underwent mammography with all imaging modes during 2012-2016. Patient and phantom AGD were estimated using accepted European and International Atomic Energy Agency protocols for dosimetry and were compared across imaging modes using a paired t test with Bonferroni correction. RESULTS: Phantom data showed that the imaging modes with the lowest to highest AGDs were system 1 2D, followed by system 2 2D and system 2 3D, which had comparable values (p = 0.6), followed by system 1 CESM, and then by system 2 2D plus 3D. One hundred eighty views in 45 patients showed that the system 1 CESM AGD was 1.8 times greater than the system 1 2D AGD (p < 0.001), 1.2 times greater than the system 2 2D AGD (p < 0.001), 1.2 times greater than the system 2 3D AGD (p < 0.001), and 0.6 times less than the system 2 2D plus 3D AGD (p < 0.001). CONCLUSION: The CESM dose for system 1 is within an acceptable range as compared with other commonly performed mammographic examinations and should not preclude its use as a diagnostic breast imaging tool.

Histogram analysis of whole-lesion enhancement in differentiating clear cell from papillary subtype of renal cell cancer.

PURPOSE: To compare histogram analysis of voxel-based whole-lesion (WL) enhancement to qualitative assessment and region-of-interest (ROI)-based enhancement analysis in discriminating the renal cell cancer (RCC) subtype clear cell RCC (ccRCC) from papillary RCC (pRCC). MATERIALS AND METHODS: In this institutional review board-approved, HIPAA-compliant retrospective study, 73 patients underwent magnetic resonance (MR) imaging prior to surgery for RCC between January 2007 and January 2010. Three-dimensional fat-suppressed T1-weighted gradient-echo corticomedullary phase acquisitions, obtained before and after contrast agent administration, were transferred to a workstation at which automated registration followed by semiautomated segmentation of the RCC was performed. Percent enhancement was computed on a per-voxel basis: (SI(post) - SI(pre))/SI(pre) .100, where SI(pre) and SI(post) indicate signal intensity before and after contrast enhancement, respectively. The WL quantitative parameters of mean, median, and third quartile enhancement and histogram distribution parameters kurtosis and skewness were computed for each lesion. WL enhancement parameters were compared with ROI-based analysis and qualitative assessment with regards to diagnostic accuracy and interreader agreement in differentiating ccRCC from pRCC. RESULTS: There were 19 pRCCs and 55 ccRCCs at pathologic examination. ccRCC had significantly higher WL mean, median, and third quartile enhancement compared with pRCC and hade significantly lower kurtosis and skewness (all P < .001). Third quartile enhancement had the highest accuracy (94.6%; area under the curve, 0.980) in discriminating ccRCC from pRCC, which was significantly higher than the accuracy of qualitative assessment (86.0%; P = .04) but not significantly higher than that of ROI enhancement (89.2%; P = .52). WL enhancement parameters had higher interreader agreement (κ = 0.91-1.0) compared with ROI enhancement or qualitative assessment (κ = 0.83 and 0.7, respectively) in discriminating ccRCC from pRCC. CONCLUSION: WL enhancement histogram analysis is feasible and can potentially be used to differentiate ccRCC from pRCC with high accuracy. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12111281/-/DC1.

COVID-19 Vaccine-Associated Subclinical Axillary Lymphadenopathy on Screening Mammogram.

BACKGROUND: Women who received a COVID-19 vaccination may display subclinical unilateral axillary lymphadenopathy on screening mammography, which can appear suspicious for malignancy, leading to additional diagnostic evaluation. PURPOSE: To evaluate the prevalence of subclinical unilateral axillary lymphadenopathy (sLAD) on screening mammogram in women who received either the first or second dose of the Pfizer-BioNTech (Pfizer) or Moderna COVID-19 vaccines compared to women who have not. MATERIALS AND METHODS: In this IRB-approved, HIPAA complaint study from 12/14/2020 to 4/14/2021, 1027 patients presented for screening mammography and met study inclusion criteria. Patients with history of baseline lymphadenopathy or prior cancer diagnosis were excluded. RESULTS: Of the 1027 women, 43 were recalled for unilateral sLAD. 34 women received a COVID-19 vaccination ipsilateral to the sLAD (Pfizer n=19, 44.2%; Moderna n=15, 34.9%), 9 did not (20.9%). Incidence of unilateral axillary sLAD was significantly higher (p-value<0.01) in those who received a COVID-19 vaccination within approximately 7 weeks preceding screening mammogram. 13.2% of patients who received the Pfizer vaccine and 9.5% of patients who received the Moderna vaccine developed sLAD. Moderna's vaccine elicited a more robust reaction in the elderly (Moderna 63.7 years vs. Pfizer 59.7 years). For both vaccines, sLAD resolved on average 46.5 days after the last COVID-19 vaccine (p=0.44). CONCLUSION: Women who have received either mRNA COVID-19 vaccines may benefit from scheduling their screening mammogram before vaccination or consider delaying screening mammography 8 weeks. While Pfizer may have an overall more robust immune response, Moderna may elicit a stronger immune response in elderly women. SUMMARY: Women who received a COVID-19 vaccination before screening mammography were significantly more likely to present with subclinical axillary lymphadenopathy than women who did not receive the vaccine. KEY RESULTS: 13.2% of women who received a Pfizer-BioNTech vaccine exhibited subclinical axillary lymphadenopathy compared to 9.5% of those who received the Moderna vaccine. Only 1.2 % of those who did not receive a vaccine presented with subclinical unilateral axillary lymphadenopathy. The average time of resolution of the lymphadenopathy on diagnostic mammogram was 46.5 days overall, with Pfizer-BioNTech taking 50.7 days and Moderna 41.5 days.

Percutaneous image-guided cryoablation of spinal metastases: A systematic review.

Percutaneous cryoablation (PCA) is a minimally invasive technique that has been recently used to treat spinal metastases with a paucity of data currently available in the literature. A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Prospective or retrospective studies concerning metastatic spinal neoplasms treated with current generation PCA systems and with available data on safety and clinical outcomes were included. In the 8 included studies (7 retrospective, 1 prospective), a total of 148 patients (females = 63%) underwent spinal PCA. Tumors were located in the cervical (3/109 [2.8%], thoracic (74/109 [68.8%], lumbar (37/109 [33.9%], and sacrococcygeal (17/109 [15.6%] regions. Overall, 187 metastatic spinal lesions were treated. Thermo-protective measures (e.g., carbo-/hydro-dissection, thermocouples) were used in 115/187 [61.5%] procedures. For metastatic spinal tumors, the pooled mean difference (MD) in pain scores from baseline on the 0-10 numeric rating scale was 5.03 (95% confidence interval [CI]: 4.24 to 5.82) at a 1-month follow-up and 4.61 (95% CI: 3.27 to 5.95) at the last reported follow-up (range 24-40 weeks in 3/4 studies). Local tumor control rates ranged widely from 60% to 100% at varying follow-ups. Grade I-II complications were reported in 9/148 [6.1%] patients and grade III-V complications were reported in 3/148 [2.0%]) patients. PCA, as a stand-alone or adjunct modality, may be a viable therapy in appropriately selected patients with painful spinal metastases who were traditionally managed with open surgery and/or radiation therapy.

Is there a doctor on the plane? A review of in-flight emergencies for the on-board radiologist.

In-flight medical emergencies (IFME) are the acute on-service events involving illness or injury to a passenger with the potential for long-term health compromise. With the continuously rising number of flights available, both domestically and internationally, it is conceivable that the number of IFMEs will similarly continue to rise. Although most of these instances are relatively self-limited, the rare instance of a severe occurrence justifies preparation, both from in-flight staff and healthcare providers traveling on these flights. Given these events' sporadic nature and the variable availability of medical support, all physicians need to understand their in-flight ethical and legal capabilities, the available medical supplies, and the most likely etiologies to manage such situations successfully. Most radiologists rarely utilize the hands-on, clinical skills developed in medical school or internship for emergencies beyond allergic contrast reactions. Therefore, they may not be adept in caring for patients during an IFME. As such, we present a thorough overview and literature review for the radiologist regarding the management of various acute IFMEs, with consideration for ethical and legal precedence and a review of medical equipment available on-board.

Motivation: how to create a cohort of engaged, energized, and happy radiology trainees.

Burnout among physicians continues to be a "hot topic" as medical culture struggles to adapt to the changing marketplace, where clinical demands are ever increasing but healthcare systems are pivoting to prefer value and cost-savings. To date, many attempts to understand and battle burnout center around the individual physician, rather than the system, limiting the medical community's ability to counter it successfully. The training environment is a common nidus for burnout. By promoting an understanding of motivation, happiness, and engagement in the workplace, we suggest several changes that training programs can make to minimize burnout and promote resident wellness. Creating a culture of support, promoting a positive work environment, building a cohesive team, and encouraging wellness both inside and outside the workplace stands to create engaged, happy, and motivated trainees who will hopefully continue to promote those strategies as they advance their careers.

Thyroid Fine Needle Aspiration: Successful Prospective Implementation of Strategies to Eliminate Unnecessary Biopsy in the Veteran Population.

OBJECTIVE: Thyroid nodules are prevalent in over half the general population. Several multidisciplinary societies have management recommendations. However, the majority of data to support these guidelines are derived from studies of predominantly younger and female populations. This study's aim was to evaluate characteristics of thyroid nodules in a largely older and male Veteran population and apply these findings prospectively to reduce unnecessary thyroid fine needle aspiration (FNA). MATERIALS AND METHODS: Over a 4-year period, all ultrasound-guided FNA of thyroid nodules performed in our department were reviewed. Sonographic features, patterns, and histopathology were evaluated. A prospective strategy of avoiding FNA in all lesions matching imaging patterns of benignity was implemented and positive predictive value (PPV) of malignancy was calculated and compared to the retrospective data. RESULTS: Retrospectively, FNA was performed on 351 successive thyroid nodules, 9 of which were malignant. Statistically significant malignant features include presence of microcalcifications, irregular or amorphous morphology, taller-than-wide shape, spiculated margins, vascularity, and lymphadenopathy. PPV of thyroid FNA was 2.6% in this period. Four sonographic patterns were 100% specific for benignity, including: "spongiform," "cyst with a colloid clot," "giraffe," and "white knight" patterns. Over 23 months, prospective avoidance of FNA of lesions characterized as a benign pattern (159 nodules) was implemented and PPV was calculated as 7.2% resulting in a cost savings of $477,000. CONCLUSION: Four sonographic patterns were 100% specific for benignity in the older and predominantly male Veteran population. Strict prospective application of avoiding biopsy in these benign patterns resulted in a decrease of unnecessary biopsies, decrease in patient morbidity, and improved allocation of health care resources.

Management of BIRADS 3, 4A, and 4B Lesions Diagnosed as Pure Papilloma by Ultrasound-Guided Core Needle Biopsy: Is Surgical Excision Necessary?

RATIONALE AND OBJECTIVES: There is lack of consensus on managing papillomas due to varied upgrade rates in the literature related to variability in the studied populations. We specifically studied upgrade rates of pure papilloma diagnosed with ultrasound core biopsy (UCB) using spring-loaded (SLB) and vacuum-assisted (VAB) biopsy devices in patients with low-to-intermediate pre-test probability for malignancy on imaging. MATERIALS & METHODS: From 01/01/2008 to 06/30/2016, 227 patients with 248 pure papillomas classified as BI-RADS 3, 4a, and 4b were diagnosed by UCB and underwent surgical excision or clinical and/or imaging follow-up. Imaging features, biopsy device, and final pathology were documented. RESULTS: 177 lesions were biopsied with SLB (14-gauge) and 71 lesions with VAB (9-13 gauges). At surgery, upgrade rates to high-risk lesions and malignancy for SLB were 14.3% (22/154) and 1.9% (3/154), and for VAB were 3.5% (2/57) and 0% (0/57), respectively (p < 0.05). The combined surgical upgrade rate to high-risk lesions and malignancy was 11.4% (24/211) and 1.4% (3/211), respectively. The overall upgrade rate (including surgical and clinical and/or imaging follow-up) to high-risk lesions and malignancy was 9.7% (24/248) and 1.2% (3/248), respectively. No ultrasound features were predictive of upgrade. Rates of complete excision were 7.1% (11/154) for SLB and 19.3% (11/57) for VAB (p < 0.05). CONCLUSION: BI-RADS 3, 4a, or 4b masses biopsied with UCB revealed pure papilloma upgrade to malignancy in less than 2% of cases. SLB was associated with greater upgrades compared with VAB. Therefore, follow-up imaging is a reasonable alternative to excision, particular in those sampled by VAB. Excision could be considered if the diagnosis of a high-risk lesion would change clinical management.

Comparison of Contrast-Enhanced Mammography With Conventional Digital Mammography in Breast Cancer Screening: A Pilot Study.

PURPOSE: To perform a pilot evaluation of contrast-enhanced mammography (CEM) for screening to determine whether it can improve accuracy and reader confidence in diagnosis. METHODS AND MATERIALS: This institutional review board-approved reader study was comprised of 64 de-identified CEM cases acquired from December 1, 2014, to June 7, 2016, including 48 negative, 5 biopsy-proven benign, and 11 biopsy-proven malignancies. Negative cases were followed for at least 2 years without evidence of cancer. Ten breast imagers of varying experience first rated the low-energy (LE) mammogram and then the CEM examination using BI-RADS categories and a 5-point Likert scale for confidence in diagnosis. RESULTS: There were 635 out a total possible 640 complete reader interpretations included in this analysis. The remaining five incomplete interpretations were excluded. Median sensitivity and specificity improved with the addition of CEM (sensitivity: 0.86 [95% confidence interval {CI}: 0.74-0.95] versus 1 [95% CI: 0.83-1.00], specificity: 0.85 [95% CI: 0.64-0.94] versus 0.88 [95% CI: 0.80-0.92]). Individual receiver operating characteristic curves showed significant improvement with CEM (mean area under the curve increase = 0.056 [95% CI: 0.015-0.097], P = .002). The addition of CEM significantly improved average confidence in 5 of 10 readers when compared with LE (P < .0001) and improved pooled confidence across all tissue density categories, except the almost entirely fatty category. There was a trend toward improved confidence with increasing tissue density with CEM. Degree of background parenchymal enhancement did not affect readers' level of improvement in confidence when interpreting CEM. SUMMARY: CEM improved reader performance and confidence compared with viewing only LE, suggesting a role for CEM in breast cancer screening for which larger trials are warranted.

Deciphering the Breast Density Inform Law Movement: Implications for Practice.

Although dense breast tissue is a normal and routine finding on screening mammography, dense breast tissue is associated with an independent increased risk for breast cancer. It is well known that screening mammography has a decreased sensitivity for cancer detection in women with dense breasts. Over the past decade, there has been increased interest generated among patients, physicians, and legislators regarding how best to screen dense-breasted women culminating in 2009 with the passage of a breast density notification law in Connecticut. Since that time, over half the United States has passed similar notification laws. Despite this, controversy remains as to the optimal supplemental screening modality to complement mammography as each imaging modality (digital breast tomosynthesis, whole breast ultrasound, magnetic resonance imaging, contrast-enhanced mammography, and molecular breast imaging) has variable benefits and limitations.

Incidental Suspicious Regional Lymph Nodes on Breast Sonography: Is Sampling Necessary?

Suspicious regional lymph nodes may be incidentally identified on breast ultrasound examinations in patients who present for sonographic evaluation without a known or a suspected breast malignancy, and there is a paucity of data on whether biopsy should be performed. This study aims to characterize incidental sonographically detected suspicious regional lymph nodes and determine whether tissue sampling or follow-up imaging is required. A total of 40,773 consecutive breast ultrasounds were reviewed. Overall, 7 women with nonpalpable, incidental, suspicious axillary or supraclavicular lymph nodes in an otherwise unremarkable breast and without history of malignancy or systemic disease were identified. In all, 5 women with 6 nodes underwent ultrasound-guided fine needle aspiration and 2 women with 3 nodes were recommended follow-up ultrasound. Follow-up imaging, cytology, and all-cause clinical data were reviewed to evaluate outcomes. All 6 biopsied lymph nodes (mean = 1.5cm) were benign on cytology. Follow-up imaging was available for 3 nodes (mean = 2.6 years), with all-cause follow-up for all nodes of 2.2 years. In the follow-up group, 3 lymph nodes (mean = 1.6cm) were monitored (mean = 4.3 years) with all-cause follow-up of 4.7 years. No new cancers, growth, or suspicious features were found in these nodes during follow-up for either group of women. In conclusion, women without history of prior malignancy or systemic disease with incidentally detected, nonpalpable, suspicious regional lymph nodes with an otherwise normal breast ultrasound examination underwent fine needle aspiration or were recommended short-term follow-up ultrasound. No indeterminate features or malignancies were observed at the time of tissue sampling or developed over several years of follow-up. Avoiding sampling of these nodes would reduce patient morbidity and health care costs.

Pseudoangiomatous Stromal Hyperplasia of the Breast: Multimodality Review With Pathologic Correlation.

Pseudoangiomatous stromal hyperplasia (PASH) is a rare benign breast condition. PASH is thought to be hormonally responsive, and it is usually identified in premenopausal and perimenopausal women. PASH may also be seen in postmenopausal woman on hormone replacement therapy (HRT). Approximately 53% of patients with PASH present with abnormalities on screening mammography, and 44% of patients with PASH present with palpable abnormalities. On imaging studies, PASH appears similar to fibroadenomas. On mammography, PASH is usually seen as a noncalcified, circumscribed mass. On ultrasound, PASH often appears as an oval, circumscribed, hypoechoic mass. On magnetic resonance imaging, PASH usually has progressive (Type 1) enhancement, and high-signal slit-like spaces may be seen on T2-weighted and short tau inversion recovery (STIR) images. The slit-like spaces correspond to empty clefts within acellular hyalinized stroma on histopathology. PASH may be mistaken for a low-grade angiosarcoma on pathologic examination. While angiosarcoma has true vascular spaces, PASH has a network of pseudoangiomatous slit-like clefts. Women with biopsy-proven PASH usually undergo follow-up imaging. Surgical excision may be considered for larger lesions and in women at an increased risk for developing breast cancer. In the future, additional studies are needed to provide definitive data regarding appropriate management and long-term outcomes for women with PASH. PASH has become increasingly recognized, but the literature regarding the imaging features of PASH is scarce. This paper reviews the imaging and pathologic features of PASH and some processes that may simulate PASH are discussed. Features of PASH on mammography, ultrasound, MRI, and nuclear medicine studies are discussed with pathologic correlation.

Spindle cell lesions of the breast: Multimodality imaging and clinical differentiation of pathologically similar neoplasms.

Spindle cell lesions of the breast comprise a wide-range of entities including reactive, benign and malignant proliferations. They can be pathologically challenging to differentiate as there is often immunohistochemical and morphologic similarities with characteristic spindle shaped cellular patterns. Radiological and pathological correlation is essential. Radiology detects, defines the size and extent, and assists in localizing the lesions. Pathology confirms the diagnosis and provides prognostic parameters. Familiarity with the clinicoradiological features of these diagnostically challenging lesions helps to establish an accurate pathological diagnosis and subsequent clinical decision making.

Early Evidence of Cardiotoxicity and Tumor Response in Patients with Sarcomas after High Cumulative Dose Doxorubicin Given as a Continuous Infusion.

BACKGROUND: Despite the dose-dependent response rate of sarcomas to doxorubicin, clinicians limit its cumulative dose due to cardiotoxicity. This study evaluates early evidence of cardiotoxicity in patients treated with high-dose doxorubicin given as a continuous infusion. METHODS: Data was collected on patients who received 90 mg/m2 doxorubicin as a continuous infusion and 10 gm/m2 ifosfamide for up to 6 cycles as part of a phase II study. Cardiotoxicity was assessed with serial echocardiograms or multigated acquisition scans and serum brain natriuretic peptide and troponin levels. Tumor responses were determined by serial radiographic imaging per RECIST. RESULT: Out of the 48 patients enrolled, no patient developed heart failure symptoms; however, 4 out of the 38 (10%) patients with serial left ventricular ejection fraction assessments developed subclinical cardiotoxicity (asymptomatic drop in LVEF ≥ 10%). Twenty-three patients received all six 72-hour cycles of doxorubicin with a mean cumulative dose of 540 mg/m2. Among these patients, 4% (n = 1) developed subclinical cardiotoxicity. In the advanced disease group (n = 39), patients with a complete or partial response received a higher mean cumulative dose than those with stable disease (p < 0.033). CONCLUSIONS: Doxorubicin cardiotoxicity can be limited by administering doxorubicin as a continuous infusion, allowing higher cumulative dosing to maximize efficacy.

Stereotactic Biopsy of Segmental Breast Calcifications: Is Sampling of Anterior and Posterior Components Necessary?

RATIONALE AND OBJECTIVES: Core needle biopsy results of segmental calcifications on mammography can have direct impact on surgical management. Although dependent on breast size, cancer spanning greater than 5 cm is usually treated with mastectomy, and cancer less than 5 cm is managed with lumpectomy. Approach to stereotactic biopsy of morphologically similar segmental calcifications that span more than 5 cm on mammography varies geographically and is currently largely based on preference of the surgical or medical oncology colleagues. Some clinicians prefer biopsy of the anterior and posterior aspects of the abnormality, whereas others believe a single biopsy within the abnormality is adequate. There is insufficient data to support whether a single biopsy of calcifications is adequate to establish the need for mastectomy, or if pathology-proven cancer in the anterior and posterior components to define the extent of disease is required. This study aims to evaluate concordance rates of paired biopsies of suspicious segmental mammographic calcifications. MATERIALS AND METHODS: From a 5-year review of our imaging database, 32 subjects were identified with breast imaging reporting and data system (BI-RADS) 4 or 5 segmental calcifications on mammography who underwent anterior and posterior stereotactic biopsies. The paired biopsy results were independently analyzed for concordance on benign, high-risk, or malignant pathology. RESULTS: Of the 32 cases, there was perfect agreement (32/32 cases = 100% concordance, 95% confidence interval = 89.3-100%) in anterior and posterior pairs in benign, high-risk, or malignant findings (kappa = 1, P < 0.001). CONCLUSIONS: The absence of data on pathological concordance in anterior and posterior aspects of suspicious, morphologically similar, segmental calcifications spanning 5 cm or more has led to a varied clinical approach to stereotactic biopsy. The 100% rate of pathological concordance in our study suggests that a single biopsy is adequate for diagnosis and representative of the whole mammographic abnormality. Implementation of this approach will potentially reduce unnecessary biopsies and surgeries, minimize healthcare costs, and decrease patient morbidity.

Both cell fusion and transdifferentiation account for the transformation of human peripheral blood CD34-positive cells into cardiomyocytes in vivo.

BACKGROUND: Adult human peripheral blood CD34-positive (CD34+) cells appear to transform into cardiomyocytes in the injured hearts of severe combined immunodeficient mice. It remains unclear, however, whether the apparent transformation is the result of transdifferentiation of the donor stem cells or of fusion of the donor cell with the cardiomyocyte of the recipients. METHODS AND RESULTS: We performed flow cytometry analyses of cells isolated from the hearts of mice that received human CD34+ cells. Human HLA-ABC antigen and cardiac troponin T or Nkx2.5 were used as markers for cardiomyocytes derived from human CD34+ cells, and HLA-ABC and VE-cadherin were used to identify the transformed endothelial cells. The double-positive cells were collected and interphase fluorescence in situ hybridization was used to detect the expression of human and mouse X chromosomes in these cells. We found that 73.3% of nuclei derived from HLA+ and troponin T+ or Nkx2.5+ cardiomyocytes contain both human and mouse X chromosomes and 23.7% contain only human X chromosome. In contrast, the nuclei of HLA-, troponin T+ cells contain only mouse X chromosomes. Furthermore, 97.3% of endothelial cells derived from CD34+ cells contained human X chromosome only. CONCLUSIONS: Thus, both cell fusion and transdifferentiation may account for the transformation of peripheral blood CD34+ cells into cardiomyocytes in vivo.