Understanding the histogenesis of a HRAS-PIK3R1 co-driven metastatic metaplastic breast carcinoma associated with squamous metaplasia of lactiferous ducts.

Metaplastic breast carcinoma (MBC) represents a heterogeneous group of aggressive primary breast cancers that can show differentiation into carcinomatous and sarcomatous elements. Due to its rapid growth, this malignancy can replace precursor lesions, which remain unknown in most cases. Herein, we describe a MBC presenting as a deceptive post-biopsy hematoma. Histopathological and immunohistochemical evaluation of the primary tumor revealed a squamous cell carcinoma arising in a background of squamous metaplasia of lactiferous ducts (SMOLD). In the absence of ductal carcinoma in situ, we consider SMOLD as a nonobligatory precursor of MBC. The tumor showed 'dedifferentiation' into spindle, mucin-producing, osteoclast-like giant cell and fibromatosis-like carcinoma. Next-generation sequencing revealed the driver mutations HRASQ61R and PIK3R1c.1738_1745+2del in addition to MYH11S638L and amplification of ERCC5 and FGF14, which were potential contributors to tumor phenotype. Tumor dedifferentiation was probably facilitated by epithelial-to-mesenchymal transition (EMT) with aberrant expression of platelet and endothelial adhesion molecule-1, leading to early metastasis via hematogenous route rather than lymphatic. The co-occurrence of phosphoinositide 3-kinase and mitogen-activated protein kinase pathway abnormalities along with EMT could mediate divergent growth in breast cancer.

To foster healing among adolescents and young adults with cancer: what helps? What hurts?

PURPOSE: The physical and emotional well-being of adolescents and young adults with cancer (AYA) rests on the ability of all concerned to promote helpful forms of care and reduce hurtful forms. The purpose of this study was to identify aspects of behavior that may promote or inhibit healthy psychosocial adjustment for this age-defined population. METHOD: Seventeen young adult cancer survivors participated in focus groups to discuss what people said or did that they found helpful or hurtful. Inductive and deductive techniques of coding and analysis of these qualitative data were performed. RESULTS: Survivors reported being the recipients of positive and negative communications and behaviors of an informational, practical, interpersonal, and/or emotional character. Most common were comments and actions in the interpersonal realm. More helpful than hurtful comments were reported, except in the informational category, where the "bad news" about cancer and the style of information-sharing created hurt. CONCLUSION: How people communicate information, tasks, and feelings to AYA patients and survivors affects how they experience their illness and think about themselves and their current and future situations. All parties-doctors, other medical providers, family members, and friends-need to attend to the manner as well as content of their communications and interactions with AYAs and to the social and emotional context within which communication and interaction occurs. Specific recommendations for the care of AYA cancer patients are offered, emphasizing the importance of attending to the cognitive capabilities and unique developmental challenges associated with adolescence and young adulthood.

A clinicopathological study of fibroadenomas with epithelial proliferation including lobular carcinoma in-situ, atypical ductal hyperplasia, DCIS and invasive carcinoma.

BACKGROUND: Fibroadenoma is a benign mixed tumor composed of epithelial and non-epithelial components. The epithelial component of a fibroadenoma may exhibit proliferation, including lobular carcinoma in-situ, atypical ductal hyperplasia, DCIS and rarely, invasive breast carcinoma. OBJECTIVE: In this series of 30 cases of fibroadenoma with epithelial proliferation, we assessed the radiological and histopathological findings of each entity. METHOD: A retrospective review was performed to identify all fibroadenomas diagnosed at our institution between January 2012 and May 2018. RESULTS: In a total of 1523 consecutive cases of fibroadenomas, thirty cases had epithelial proliferations with an overall prevalence of 1.97%. Eight cases had fibroadenoma with lobular carcinoma in-situ, six cases had atypical ductal hyperplasia, ten cases had DCIS and six cases had invasive carcinoma. In cases of fibroadenomas with lobular carcinoma in-situ, 62.5% of the cases the neoplasia was confined to the fibroadenoma whereas only 10% of the cases with DCIS showed confinement to the fibroadenoma (p = 0.036). The most common radiological finding was the presence of a mass. The BI-RADS scores were 4 and above in all cases (p > 0.05). CONCLUSION: In our study population, the most common type of carcinoma arising in fibroadenomas was DCIS, followed by lobular carcinoma in-situ. Lobular carcinoma in-situ was more likely to be confined to the fibroadenoma while most DCIS involved surrounding breast tissue.

Emotional expression in children treated with ADHD medication: development of a new measure.

OBJECTIVE: Although existing instruments contain items addressing the effect of ADHD medications on emotional expression, a review of measures did not yield any instruments that thoroughly evaluated positive and negative aspects of emotional expression. METHOD: The Expression and Emotion Scale for Children (EESC), a parent-report measure, was developed from an analysis of qualitative data from parent focus groups and expert opinion. Data from 179 parents and children treated with stimulants or atomoxetine are used to examine the psychometric properties of the EESC. RESULTS: The EESC demonstrates good internal consistency and test-retest reliability. A factor analysis yields three factors (positive, flat, and emotional lability) that were consistent with the predicted structure of the measure. Small to moderate correlations between the EESC and psychological symptom measures are found, with the strength of the relationships varying by symptom measure. CONCLUSION: The EESC shows appropriate psychometric properties and is appropriate for use in clinical and research settings.

Neuroleptic malignant syndrome from aripiprazole in an agitated pediatric patient.

OBJECTIVE: Neuroleptic malignant syndrome was induced by aripiprazole in a 12 1/2-year-old boy. The patient had a history of reactive airway disease, pervasive developmental disorder, and learning disability. METHOD: The patient was interviewed and examined, and additional history was taken from the medical records. The Naranjo adverse drug reaction rating scale was applied. RESULTS: The patient developed neuroleptic malignant syndrome 2 days after starting aripiprazole 10 mg/d. This patient had no history of exposure to dopamine-blocking drugs or selective serotonin reuptake inhibitors or of neurological disorder, movement disorder, or substance use. Aripiprazole discontinuation and supportive treatment led to resolution. The Naranjo scale indicates high probability of neuroleptic malignant syndrome from aripiprazole. CONCLUSIONS: Aripiprazole can rapidly induce neuroleptic malignant syndrome in adolescents.

Efficacy and safety of atomoxetine in adolescents with attention-deficit/hyperactivity disorder and major depression.

This double-blind study examined efficacy and safety of atomoxetine (ATX; < or =1.8mg/kg per day) in adolescents aged 12-18 with Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) diagnoses of both attention-deficit/hyperactivity disorder (ADHD) and co-morbid major depressive disorder (MDD). Diagnoses were confirmed by the Kiddie Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version and persistently elevated scores on the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV, Parent version, Investigator-administered and -scored (ADHDRS-IV-Parent:Inv, > or =1.5 standard deviations above age and gender norms) and Children's Depression Rating Scale-Revised (CDRS-R, > or = 40). Patients were treated for approximately 9 weeks with ATX (n = 72) or placebo (n = 70). Mean decrease in ADHDRS-IV-Parent:Inv total score was significantly greater in the ATX group (-13.3 +/- 10.0) compared with the placebo group (-5.1 +/- 9.9; p < 0.001). Mean CDRS-R score improvement was not significantly different between groups (ATX, -14.8 +/- 13.3; placebo, -12.8 +/- 10.4). Rates of treatment-emergent mania did not differ between groups (ATX, 0.0%; placebo, 1.5%). ATX treatment was associated with significantly more nausea and decreased appetite (p = 0.002; p = 0.003). No spontaneously reported adverse events involving suicidal ideation or suicidal behavior occurred in either group. ATX was an effective and safe treatment for ADHD in adolescents with ADHD and MDD. However, this trial showed no evidence for ATX of efficacy in treating MDD.

Fluoxetine 40-60 mg versus fluoxetine 20 mg in the treatment of children and adolescents with a less-than-complete response to nine-week treatment with fluoxetine 10-20 mg: a pilot study.

OBJECTIVE: The aim of this study was to compare fluoxetine dosage titration to 40-60 mg/day with fixed fluoxetine 20-mg/day treatment for an additional 10 weeks in pediatric outpatients with major depressive disorder (MDD) who had not met protocol-defined response criteria after 9-week acute fluoxetine treatment. METHODS: Patients unresponsive (less than or equal to 30% decrease in Children's Depression Rating Scale-Revised [CDRS-R] score) after 9-week fluoxetine treatment were randomly reassigned to continue at 20 mg/day or to increase to 40 mg/day. After 4 weeks, patients unresponsive to 40 mg/day could receive 60 mg/day. RESULTS: Twenty-nine (29) patients, 9-17 years of age, received fluoxetine 40-60 mg/day (n = 14) or 20 mg/day (n = 15). At the conclusion of this study phase, 10 patients (71%) on 40-60 mg/day met the response criteria, versus 5 patients (36%) on 20 mg/day (p = 0.128). Mean CDRS-R scores improved in both treatment groups (fluoxetine 40-60 mg/day, -9.4; fluoxetine 20 mg/day, -1.5; p = 0.099). Adverse events were similar in both groups. However, this study phase was statistically underpowered for detecting differences between treatment groups. CONCLUSION: More than two thirds of patients whose dosage was increased responded within 10 weeks, suggesting dose escalation may benefit some patients. Approximately one third of patients unresponsive to initial treatment with fluoxetine 20 mg responded to this fixed dosage within another 10 weeks. Fluoxetine 20-60 mg/day was well tolerated.

Short-term efficacy of methylphenidate: a randomized, double-blind, placebo-controlled trial among survivors of childhood cancer.

PURPOSE: Children surviving acute lymphoblastic leukemia (ALL) and malignant brain tumors (BTs) have a higher incidence of attention and learning problems in school than do their healthy peers. The present study tests the hypothesis that the psychostimulant methylphenidate (MPH) improves cognitive and social functioning among these patients. PATIENTS AND METHODS: We report on 83 long-term survivors of ALL and BT identified as having attentional deficits on behavioral testing and parent or teacher report, and problems with academic achievement. The 47 male and 36 female patients ranged from 0.6 to 14.3 years (median, 5.4 years) of age at diagnosis and 6.7 to 17.9 years (median, 11.9 years) of age at participation. The patients (40 ALL, 43 BT) participated in a randomized, double-blind, 3-week home cross-over trial of placebo (bid), low-dose MPH (0.3 mg/kg; maximum dose, 10 mg bid), and moderate-dose MPH (0.6 mg/kg; maximum dose, 20 mg bid). The primary end points were weekly teacher and parent reports on the Conners' Rating Scales and Social Skills Rating System. RESULTS: Compared to placebo, significant improvement with MPH was reported by teachers and parents on the Conners' Rating Scales and by teachers on the Social Skills Rating System. However, no consistent advantage of moderate dose over low dose was observed. Of those participating, 66 (79.5%) of the 83 patients continued on best clinical management. CONCLUSION: Treatment with MPH can at least temporarily reduce some attentional and social deficits among survivors of childhood ALL and BT. Long-term follow-up will reveal those subsets of patients who are more likely to benefit from MPH.

Wound fluid bacterial levels exceed tissue bacterial counts in controlled porcine partial-thickness burn infections.

In the present study, an established controlled burn wound model was used to test the hypothesis that controlled surface contamination with is capable of generating a noninvasive method for the creation of a reproducible deep tissue burn wound infection. Using a liquid tight-wound chamber in Yorkshire pigs, partial-thickness burns were inoculated with saline-immersed for 24 hours. Noninoculated burns and unwounded skin immersed in normal saline served as controls. Bacterial cultures of wound fluid were performed daily, and tissue biopsies for bacteriological and histological evaluations were performed on days 1, 3, and 5. was only recovered from -inoculated wounds (tissue and fluid), whereas all controls contained endogenous only. The number of colony-forming units per gram of wound tissue did not correlate with the bacterial counts found in the overlying wound fluid for any wounds. Fluid counts were consistently higher than tissue counts by two logs. -inoculated wounds showed three times deeper tissue destruction than control wounds. Obtaining consistently deep tissue colonization without cross-contamination among wounds, this study introduces a noninvasive model for controlled burn wound infection suitable for future investigations regarding the efficacy of topical antibiotic wound treatment in experimental burns.

Automated whole breast ultrasound.

Bilateral whole breast (screening) ultrasound has been well established in multiple single- and multi-institution published studies as a valuable adjunct to mammography screening for early detection of breast cancer. However, implementation of screening breast ultrasound programs has been limited and has met with resistance because of the number of potential false positives generated by ultrasound screening, and the lack of available personnel to perform the examination. Automated breast ultrasound, which has recently been approved by the US Food and Drug Administration for use in whole-breast ultrasound screening, is a potential option for providing breast ultrasound screening on a widespread basis.

Solitary neurofibroma of the breast.

Neurofibromas are slow-growing, painless, benign nerve-sheath tumors. They occur most commonly in the dermis and subcutis and are rarely found in the breast. We report a rare case of a solitary neurofibroma of the breast in a 61-year-old asymptomatic woman.

The use of research measures in adult clinical practice.

Many psychopathology research assessment tools can be used easily and productively in clinical practice. We conducted a workshop in 2009 and 2010 at the American Psychiatric Association annual meeting designed to bring clinicians some commonly used adult research measures with broad applicability to a variety of conditions. This article reviews what was most helpful to the practicing clinicians at the workshop.

The History and Accomplishments of the LIVESTRONG Young Adult Alliance.

PURPOSE: This article outlines the history, background, and accomplishments of the LIVESTRONG Young Adult Alliance. BACKGROUND: The LIVESTRONG Young Adult Alliance, a program of the Lance Armstrong Foundation, was developed as a vehicle for a strategic plan designed to implement the Adolescent and Young Adult Oncology Progress Review Group (AYAO PRG) recommendations. The AYAO PRG was co-sponsored by Lance Armstrong Foundation and the National Cancer Institute (NCI); both LIVESTRONG and NCI provide strategic oversight and guidance to the Alliance. Highlights and accomplishments: The Alliance accomplishments include the publication of disease-specific retrospective analyses, funding of an AYA cohort study and biorepository proposal, publication of two position statements on guidelines for care of AYAs with cancer and training for AYA oncology health professionals, promotion of an international charter of rights for AYA cancer patients, creation and distribution of a survey to college health professionals, creation and implementation of a Cancer Centers Working Group and Institutional Review Board Toolkit, and continued growth and collaboration through an annual meeting. CONCLUSION: The growth and success of the Alliance has coincided with the growth of AYA oncology as a field. The collaborative environment of the Alliance draws together a diverse group of individuals united in the effort to increase survival rates and improve the quality of life for adolescents and young adults diagnosed with cancer.