HTLV-1 Presenting as an Incidental Finding after a Cosmetic Procedure.

A 44-year-old woman presented to a plastic surgeon for liposuction of the abdomen, back, and flanks, a gluteal fat transfer, and a vertical pattern breast lift and small reduction. The patient had a medical history of significantly well-controlled hypertension for 4 years treated with hydrochlorothiazide and amlodipine. She had been pregnant four times and delivered six children with two sets of twins. She was allergic to latex and denied a history of smoking. Her physical examination was unremarkable and her body mass index (BMI) was 26.1. No skin lesions were evident (Figure 1). Her preoperative laboratory findings were within normal limits, with unremarkable electrocardiogram (EKG), chest x-ray, and mammogram. The patient underwent a successful surgical procedure, and the excised breast tissue and skin were sent to pathology for routine evaluation. Surgery removed 220 g of breast tissue from the left breast and 45 g was excised from the right one. The histopathology depicted atypical T-cells in the epidermis and superficial dermis of both left and right breasts. Physical examination failed to evidence lymph-adenopathy or masses. The patient denied weight loss, night sweats, or fever; however, due to her Caribbean heritage, adult T-cell leukemia/ lymphoma was considered and submitted for further histologic workup.

NR2F1 Is a Barrier to Dissemination of Early-Stage Breast Cancer Cells.

Cancer cells can disseminate during very early and sometimes asymptomatic stages of tumor progression. Though biological barriers to tumorigenesis have been identified and characterized, the mechanisms that limit early dissemination remain largely unknown. We report here that the orphan nuclear receptor nuclear receptor subfamily 2, group F, member 1 (NR2F1)/COUP-TF1 serves as a barrier to early dissemination. NR2F1 expression was decreased in patient ductal carcinoma in situ (DCIS) samples. High-resolution intravital imaging of HER2+ early-stage cancer cells revealed that loss of function of NR2F1 increased in vivo dissemination and was accompanied by decreased E-cadherin expression, activation of wingless-type MMTV integration site family, member 1 (WNT)-dependent ß-catenin signaling, disorganized laminin 5 deposition, and increased expression of epithelial-mesenchymal transition (EMT) genes such as twist basic helix-loop-helix transcription factor 1 (TWIST1), zinc finger E-box binding homeobox 1 (ZEB1), and paired related homeobox 1 (PRRX1). Furthermore, downregulation of NR2F1 promoted a hybrid luminal/basal phenotype. NR2F1 expression was positively regulated by p38α signaling and repressed by HER2 and WNT4 pathways. Finally, early cancer cells with NR2F1LOW/PRRX1HIGH staining were observed in DCIS samples. Together, these findings reveal the existence of an inhibitory mechanism of dissemination regulated by NR2F1 in early-stage breast cancer cells. SIGNIFICANCE: During early stages of breast cancer progression, HER2-mediated suppression of NR2F1 promotes dissemination by inducing EMT and a hybrid luminal/basal-like program.

Measuring Invasive Breast Carcinoma on Core Biopsy-Is It Necessary?

CONTEXT.­: Pathologic tumor size is significant in the treatment of breast carcinoma and is routinely measured on excision. OBJECTIVE.­: To analyze the need for measuring size of invasive mammary carcinoma on biopsy. DESIGN.­: Nine hundred twenty-two cases of invasive carcinoma whose size was measured (greatest linear measurement) on biopsy and excision was correlated, including imaging when available (110 cases). RESULTS.­: Patient mean age was 62 years. Most (90%; 830 of 922) carcinomas were ductal and sampled by ultrasound and graded as follows: well, 13% (113 of 922); moderately, 58% (532 of 922), and poorly differentiated, 28% (258 of 922); 19 microinvasive not graded. Tumor mean size was 7.5 mm on biopsy and 14.4 mm on excision. Biopsy modality was as follows: ultrasound, 7.8 mm (92%, 844 of 922); mammotome, 3.3 mm (7%, 65 of 922); and magnetic resonance imaging, 5.9 mm (1%, 13 of 922). Size comparison on biopsy versus excision was biopsy > excision: 8% (72 of 922), biopsy = excision: 10% (95 of 922), and biopsy < excision: 82% (755 of 922). Half (36 of 72) of the biopsy > excision tumors were less than 5 mm, 96% (726 of 755) of biopsy < excision tumors were greater than 5 mm, while those equal on both were predominantly (88%, 84 of 95) less than 10 mm, 20% (19 of 95) of which were microinvasive. Stage changed in 600 cases, staging based on excision in 581 (63%), and staging based on biopsy in 19 (2%). Radiologic-pathologic correlation (n = 110) showed perfect concordance in 11 (10%), 83 (75%) were ±1 to 2 mm, and 16 (15%) were ± more than 3 mm. Difference between the biopsy and excision ranged from a lower limit of 1.3 mm for T1a tumors to 18 mm for T2. CONCLUSIONS.­: While most carcinomas are larger on excision, 18% (167 of 922) are larger or equal on biopsy. Factors predictive of biopsy > excision tumors include stage 1 tumors (P < .001), especially less than 5 mm, and sampled by mammotome. We recommend measuring invasive carcinoma on biopsy and excision.

Not All Ductal Carcinomas In Situ Are Created IDLE (Indolent Lesions of Epithelial Origin).

CONTEXT.­: Mammographic screening has increased the incidence of ductal carcinoma in situ (DCIS), but this has not been accompanied by a decline in the incidence of invasive carcinoma (IC). Consequently, the surgical treatment of DCIS has recently been questioned, with some advocating only surveillance (with or without neoadjuvant endocrine therapy) after a core biopsy diagnosis of DCIS. OBJECTIVES.­: To examine the predictive value of a core biopsy diagnosis of DCIS, particularly the upgrade rate to IC, and to identify associated factors. DESIGN.­: Using the pathology database, we identified 2943 cases of DCIS diagnosed on core biopsy from 2000 to 2015, of which 229 cases (8%) later had the stage upgraded to IC. RESULTS.­: Ages ranged from 25 to 90 years (mean, 59 years). The DCIS presented with calcifications in 151 of 229 cases (65.9%), was widespread in 26 of 151 cases (17%), had a mass or density present in 70 of 229 cases (31%), with heterogeneous echogenic features in 44 of those 70 cases (63%), and an enhancement upon magnetic resonance imaging in 8 of 229 cases (3.5%). Of the 229 cases, the DCIS grades were as follows: low in 29 cases (13%), intermediate in 79 cases (36%), and high in 121 cases (53%). Of the 229 cases, necrosis was present in 152 (66.4%) and was comedo necrosis in 99 cases (43%). Of the 229 cases of IC, the tumor stage was as follows: microIC in 36 (16%), T1a in 119 (52%), T1b in 35 (15%), T1c in 28 (12%), T2 in 8 (3%), and T3 in 3 cases (1%). Axillary lymph nodes were staged in 167 patients as follows: N0, 141 cases (84%); N0(i+), 14 cases (8%); and N1, 12 cases (7%). The 12 N1 cases were subclassified by T stage as follows: T1a, 1 case (8%); T1b, 4 cases (33%); T1c, 2 cases (17%); T2, 4 cases (33%); and T3, 1 case (8%). The IC cases of stage upgrading were predominantly smaller than 2 cm (218 of 229; 95%), and more than two-thirds were smaller than 0.5 cm (155 of 229; 95%), most of which were accompanied by extensive DCIS. CONCLUSIONS.­: Approximately one-half of the upgrades were associated with high-grade DCIS, especially with comedo necrosis; nevertheless, the other one-half of the upgrades were due to low- and intermediate-grade DCIS and should not be underestimated. There were few positive results from axillary lymph node biopsies, but they occurred in 3% (7 of 218) of the carcinomas smaller than 2 cm. Our findings indicate that caution is needed when DCIS cases diagnosed by core biopsy are treated nonsurgically with surveillance (with or without neoadjuvant endocrine therapy), given the number of cases (229 of 2943; 8%) that are upgraded to IC and those with axillary lymph node metastases (12 of 167; 7%).

"Low-grade squamous intraepithelial lesion, cannot exclude high-grade:" TBS says "Don't Use It!" should I really stop it?

BACKGROUND: The Bethesda System uses a two-tiered approach in the diagnosis of cervical squamous intraepithelial lesions (SILs). Occasionally, Papanicolaou (Pap) tests with evident low-grade SIL (LSIL) also have some features suggestive but not diagnostic of high-grade SIL (HSIL). This study reviews our experience with "Low-grade Squamous Intraepithelial Lesion, Cannot Exclude High-grade" (LSIL-H) and discusses the best approach to report such Paps if the LSIL-H interpretation is abandoned. METHODS: Abnormal Paps were identified between January and December 2014 that had surgical follow-up within 6 months. Their biopsy outcomes were compared. Statistical analysis was performed using Pearson's Chi-square and McNemar tests in SPSS software version 23. Statistical significance was defined as P ≤ 0.05. RESULTS: There were a total of 1049 abnormal Paps with follow-up. High-grade dysplasia/carcinoma (HGD+) was found in 8% of LSIL, 30% of LSIL-H, 52% of atypical squamous cells (ASCs), cannot rule out HSIL (ASC-H), and 77% of HSIL Paps. The detection rate of HGD+ for LSIL-H was between that of LSIL (Pearson's Chi-square test, P = 0.000) and ASC-H (P = 0.04). If LSIL-H cases are reported as ASC-H, the rate of HGD+ for the ASC-H category would decrease from 51.5% to 37.4% (McNemar test, P = 0.000). Alternatively, if LSIL-H cases are downgraded to LSIL, the rate of HGD+ for the LSIL category would rise from 7.7% to 10.4% (McNemar test, P = 0.000). Nearly 86.7% of LSIL-H cases were positive for high-risk HPV (HR-HPV) in comparison to 77.5% of LSILs, 100% of ASC-Hs, and 75% of HSILs. The sample size for HR-HPV and LSIL-H was too small for meaningful statistical analysis. CONCLUSIONS: "LSIL-H" category detects more HGD+ than LSIL, and fewer than ASC-H and HSIL. If LSIL-H is eliminated, Paps with this finding are best reported as ASC-H to ensure that women with potential HGD+ undergo colposcopy in a timely manner. Reporting LSIL-H as LSIL may delay colposcopy since management of LSIL Paps depends on multiple factors (age, HPV status, etc.).

Can p40 (Polyclonal) Replace p63 (Clone 4A4) in the Cytologic Diagnosis of Pulmonary Non-Small Cell Carcinoma?

OBJECTIVES: Differentiating squamous cell carcinoma from adenocarcinoma (ACA) in cytology specimens can be challenging. Recent literature showed p40 had higher specificity than p63 for this purpose. METHODS: We identified 190 cytology cases with p40 (polyclonal) and p63 (monoclonal clone 4A4) immunohistochemistry, including specimens from fine-needle aspirations (FNAs) and effusions. RESULTS: ACAs of lung origin stained for p40 and p63 in 21% and 20% of cases, respectively, regardless of specimen site. Among lung FNAs of primary pulmonary ACAs (n = 42), 14% were positive for p40 and 24% were positive for p63. Of the 20 pulmonary ACAs in effusions, more cases showed p40 positivity (40%) compared with FNAs, whereas p63 were positive in 15%. Among metastatic ACAs from other sites (n = 14), more cases were positive for p40 than p63. CONCLUSIONS: Polyclonal p40 yields a level of false positivity in ACAs similar to p63, which is highest in effusions and is not limited to lung origin.

Primary anorectal mucosal melanoma detected by anorectal cytology.

The detection of primary anorectal melanoma on anal cytology is a rare and challenging diagnosis. We report a case where anorectal cytology showed isolated malignant cells with oval nuclei, prominent nucleoli, and elongated wispy cytoplasmic projections. There was no evidence of squamous dysplasia or melanin pigment identified. To the best of our knowledge, this is the first reported case of a primary anorectal melanoma detected in anorectal cytology. Detection of malignancies other than squamous cell carcinoma can be seen on anorectal cytology and should be considered when there is no evidence of anal intraepithelial neoplasia. Diagn. Cytopathol. 2017;45:452-455. © 2017 Wiley Periodicals, Inc.

Posttraumatic Stress Disorder and Stressful Life Events Among Rural Women With HIV Disease.

Posttraumatic stress disorder (PTSD) and stressful life events are frequent and distressing problems for women living with HIV (WLWH). Studies have independently focused on the impact of these problems, but little work has examined the relationship between PTSD and stressful life events. Our cross-sectional study examined relationships between PTSD and recent stressful life events in WLWH. A sample of 60 women recruited through HIV community agencies in southeastern North Carolina completed the Stressful Life Events Questionnaire and the PTSD Checklist-Civilian Version (PCL-C). PTSD prevalence was high (43.2%). Two-thirds (66%) reported three or more recent life stressors. Women who experienced a higher number of recent life stressors scored higher on the PCL-C than those with fewer life stressors (p < .001). Recent stressful life events may accelerate PTSD symptoms. Findings underscore the importance of addressing mental health issues in HIV treatment settings. Implications for nursing practice are provided.

Multifocal Invasive Ductal Cancer: Distinguishing Independent Tumor Foci From Multiple Satellites.

Patients with multifocal breast cancers (MBCs) have a poorer prognosis than patients with unifocal breast cancers. Studies have attributed this to tumor size underestimation in MBC. An alternative hypothesis is that some MBCs behave in a fashion analogous to the "satellite" and "in-transit metastasis" observed in melanoma and, thereby, are more clinically aggressive. We identified 79 cases of MBC, which we classified into 2 groups: study cases defined as ≥2 morphologically similar tumor foci with ≥1 focus without in situ carcinoma (n = 21); and a control group defined as ≥2 morphologically similar or dissimilar foci with associated in situ carcinoma in all foci (n = 58). The odds of being a study case is 1.86 (95% confidence interval [CI] 1.26-2.74) times greater per unit increase in number of tumor foci (median of 4 tumor foci; P = .002). Study cases were 73.33 (95% CI = 8.91-603.16) times more likely to have lymphovascular invasion (LVI) and 14.72 (95% CI = 4.37-49.61) times more likely to have nodal metastases. Grade I/II tumors were 0.20 (95% CI = 0.07-0.59) times less likely to be study cases. There was a significant positive interaction ( P < 0.001) indicated by the relationship of LVI status and nodal status with the study case and control group. We conclude that there is a subset of MBC that presents with more numerous tumor foci and a higher rate of nodal metastasis. The aggressive behavior of these cases may be attributed to their proclivity for LVI.

Hyperactivated mTOR and JAK2/STAT3 Pathways: Molecular Drivers and Potential Therapeutic Targets of Inflammatory and Invasive Ductal Breast Cancers After Neoadjuvant Chemotherapy.

INTRODUCTION: Inflammatory breast cancer (IBC) is an aggressive and rare cancer with a poor prognosis and a need for novel targeted therapeutic strategies. Preclinical IBC data showed strong activation of the phosphatidylinositide-3-kinase/mammalian target of rapamycin (mTOR) and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways, and expression of inflammatory cytokines and tumor-associated macrophages (TAMs). PATIENTS AND METHODS: Archival tumor tissue from 3 disease types (IBC treated with neoadjuvant chemotherapy [NAC], n = 45; invasive ductal carcinoma [IDC] treated with NAC [n = 24; 'treated IDC'; and untreated IDC [n = 27; 'untreated IDC']) was analyzed for the expression of biomarkers phospho-S6 (pS6) (mTOR), phospho-JAK2 (pJAK2), pSTAT3, interleukin (IL)-6, CD68 (monocytes, macrophages), and CD163 (TAMs). Surrounding nontumor tissue was also analyzed. RESULTS: Biomarker levels and surrogate activity according to site-specific phosphorylation were shown in the tumor tissue of all 3 disease types but were greatest in IBC and treated IDC and least in untreated IDC for pS6, pJAK2, pSTAT3, and IL-6. Of 37 IBC patients with complete biomarker data available, 100% were pS6-positive and 95% were pJAK2-positive. In nontumor tissue, biomarker levels were observed in all groups but were generally greatest in untreated IDC and least in IBC, except for JAK2. CONCLUSION: IBC and treated IDC display similar levels of mTOR and JAK2 biomarker activation, which suggests a potential mechanism of resistance after NAC. Biomarker levels in surrounding nontumor tissue suggested that the stroma might be activated by chemotherapy and resembles the oncogenic tumor-promoting environment. Activation of pS6 and pJAK2 in IBC might support dual targeting of the mTOR and JAK/STAT pathways, and the need for prospective studies to investigate combined targeted therapies in IBC.

A Note of Caution: Variable Cytokeratin Staining in Sentinel Node Metastases.

Sentinel lymph node biopsy is the current standard procedure used to stage patients with breast cancer. The best histological method in evaluating sentinel nodes is highly debated among institutions and is thus not standardized. The optimal histological analysis is a balance between comprehensive evaluation of the sentinel nodes and cost effectiveness. One commonly used approach is serial sectioning and alternately staining with hemotoxylin and eosin and AE1/AE3 cytokeratin immunohistochemistry analysis. We report 2 cases of metastatic carcinoma demonstrating negative staining for AE1/AE3. This observation highlights a rare but potential pitfall to this commonly used strategy in assessing sentinel lymph node biopsies in breast cancer.

Medallion-like dermal dendrocytoma.

Medallion-like dermal dendrocytoma is a benign cutaneous neoplasm that mimics dermatofibrosarcoma protuberans histologically. The distinction between these two entities is critical to prevent unnecessary wide excisions. Herein we describe an acquired MLDD in a 55-year-old female.

Quiet eye duration is responsive to variability of practice and to the axis of target changes.

We tested the hypothesis that quiet eye the final fixation before the initiation of a movement in aiming tasks, is used to scale the movement's parameters. Two groups of 12 participants (N=24) threw darts to targets in the horizontal and vertical axes under conditions of higher (random) or lower (blocked) target variability. Supporting our predictions, random practice and target changes in the vertical axis led to longer quiet eye duration than did blocked practice and target changes in the horizontal axis. Our data suggest that quiet eye is not simply a mediating factor in accuracy, but is responsive to the task's programming demands, being influenced by the necessity to reparameterize the movement from one trial to the next.

The public's perception of dermatologists as surgeons.

BACKGROUND: Dermatologists perform more cutaneous surgical procedures than any other medical specialists, including plastic surgeons, especially for treating skin cancers, but anecdotal evidence suggests that the public may not identify dermatologists as surgeons. OBJECTIVE: Our study was designed to assess the public's perception of expertise in surgery of the skin of three medical specialties: dermatology, plastic surgery, and general surgery. We also investigated whether the physician's specialty biases people when they assess the cosmetic appearance of a surgical scar. MATERIALS AND METHODS: We administered an institutional review board-approved survey to individuals at the Emory Student Center and the Emory Dermatology Clinic. Participants rated the perceived skills and training of the different medical specialties and scored the cosmetic appearance of 16 surgical scars created by a fellowship-trained Mohs surgeon labeled as the work of different specialists. RESULTS: Results from 467 participants were overwhelmingly in favor of plastic surgeons (p<.001). The physician's specialty did not bias participants in assessing the cosmetic appearance of surgical scars. CONCLUSION: The study population had greater confidence in the surgical skills of plastic surgeons than in those of dermatologists, although participants were objective in rating the cosmesis of surgical scars, regardless of the purported surgeon's specialty. Although dermatologic surgeons must continually refine our surgical expertise, we must also educate the public about the breadth and depth of our work. The authors have indicated no significant interest with commercial supporters.

Donor and recipient envs from heterosexual human immunodeficiency virus subtype C transmission pairs require high receptor levels for entry.

Compact, glycan-restricted envelope (Env) glycoproteins are selected during heterosexual transmission of subtype C HIV-1. Donor and recipient glycoproteins (Envs) from six transmission pairs were evaluated for entry into HeLa cells expressing different levels of CD4 and CCR5. Donor and recipient Envs demonstrated efficient entry into cells expressing high levels of CD4 and CCR5, and entry declined as CCR5 levels decreased. Infectivity for all Envs was severely impaired in cells expressing low levels of CD4, even at the highest CCR5 levels. In 5/6 pairs, there was no significant difference in efficiency of receptor utilization between the donor and recipient Envs in these HeLa-derived cell lines. Thus, HIV-1 transmission does not appear to select for viruses that can preferentially utilize low levels of entry receptors.

The relationship between paramedics' level of education and degree of commitment.

INTRODUCTION: Emergency medical services (EMS) personnel attrition is a serious concern. Two fundamental psychological constructs linked to attrition are organizational and occupational commitment. OBJECTIVE: To determine if there is a relationship between a paramedic's degree of occupational/organizational commitment and the following: (1) levels of education and (2) type of employment. METHODS: This was a cross-sectional study of paramedics in 6 states that require continued paramedic national registration. The data collection instrument consisted of demographic and occupational and organizational commitment sections. For level of education, the primary independent variable, each subject was placed into 1 of 3 groups: (1) certificate, (2) associate's or bachelor's degree in EMS (degree), and (3) paramedic certificate or degree with a non-EMS postbaccalaureate degree. Type of employment (fire based vs non-fire based) was also used as an independent variable. Organizational and occupational commitment was measured using validated scales for each. Analysis of variance was used for the comparisons between levels of each of the independent variables. A P < .05 was considered significant. RESULTS: For occupational commitment, the participants with certificate level of education had a significantly higher score (88.9) than did those with either the degree (83.6) or postbaccalaureate (80.9) level of education. There were no significant differences for total organizational commitment. There were also no overall differences in occupational and organizational commitment between fire- and non-fire-based employees. CONCLUSION: Paramedic occupational commitment shows a statistically significant decrease with increased level of education. Factors associated with commitment of more highly educated paramedics need to be explored.

Nef does not contribute to replication differences between R5 pre-AIDS and AIDS HIV-1 clones from patient ACH142.

AIDS-associated, CCR5-tropic (R5) HIV-1 clones, isolated from a patient that never developed CXCR4-tropic HIV-1, replicate to a greater extent and cause greater cytopathic effects than R5 HIV-1 clones isolated before the onset of AIDS. Previously, we showed that HIV-1 Env substantially contributed to the enhanced replication of an AIDS clone. In order to determine if Nef makes a similar contribution, we cloned and phenotypically analyzed nef genes from a series of patient ACH142 derived R5 HIV-1 clones. The AIDS-associated Nef contains a series of residues found in Nef proteins from progressors 1. In contrast to other reports 123, this AIDS-associated Nef downmodulated MHC-I to a greater extent and CD4 less than pre-AIDS Nef proteins. Additionally, all Nef proteins enhanced infectivity similarly in a single round of replication. Combined with our previous study, these data show that evolution of the HIV-1 env gene, but not the nef gene, within patient ACH142 significantly contributed to the enhanced replication and cytopathic effects of the AIDS-associated R5 HIV-1 clone.

Human immunodeficiency virus type 1 Nef associates with lipid rafts to downmodulate cell surface CD4 and class I major histocompatibility complex expression and to increase viral infectivity.

Lipid rafts are membrane microdomains that are functionally distinct from other membrane regions. We have shown that 10% of human immunodeficiency virus type 1 (HIV-1) Nef expressed in SupT1 cells is present in lipid rafts and that this represents virtually all of the membrane-associated Nef. To determine whether raft targeting, rather than simply membrane localization, has functional significance, we created a Nef fusion protein (LAT-Nef) containing the N-terminal 35 amino acids from LAT, a protein that is exclusively localized to rafts. Greater than 90% of the LAT-Nef protein was found in the raft fraction. In contrast, a mutated form, lacking two cysteine palmitoylation sites, showed less than 5% raft localization. Both proteins were equally expressed and targeted nearly exclusively to membranes. The LAT-Nef protein was more efficient than its nonraft mutant counterpart at downmodulating both cell surface CD4 and class I major histocompatibility complex (MHC) expression, as well as in enhancing first-round infectivity and being incorporated into virus particles. This demonstrates that targeting of Nef to lipid rafts is mechanistically important for all of these functions. Compared to wild-type Nef, LAT-Nef downmodulated class I MHC nearly as effectively as the wild-type Nef protein, but was only about 60% as effective for CD4 downmodulation and 30% as effective for infectivity enhancement. Since the LAT-Nef protein was found entirely in rafts while the wild-type Nef protein was distributed 10% in rafts and 90% in the soluble fraction, our results suggest that class I MHC downmodulation by Nef may be performed exclusively by raft-bound Nef. In contrast, CD4 downmodulation and infectivity enhancement may require a non-membrane-bound Nef component as well as the membrane-bound form.