Integrin α6 mediates the drug resistance of acute lymphoblastic B-cell leukemia.

Resistance to multimodal chemotherapy continues to limit the prognosis of acute lymphoblastic leukemia (ALL). This occurs in part through a process called adhesion-mediated drug resistance, which depends on ALL cell adhesion to the stroma through adhesion molecules, including integrins. Integrin α6 has been implicated in minimal residual disease in ALL and in the migration of ALL cells to the central nervous system. However, it has not been evaluated in the context of chemotherapeutic resistance. Here, we show that the anti-human α6-blocking Ab P5G10 induces apoptosis in primary ALL cells in vitro and sensitizes primary ALL cells to chemotherapy or tyrosine kinase inhibition in vitro and in vivo. We further analyzed the underlying mechanism of α6-associated apoptosis using a conditional knockout model of α6 in murine BCR-ABL1+ B-cell ALL cells and showed that α6-deficient ALL cells underwent apoptosis. In vivo deletion of α6 in combination with tyrosine kinase inhibitor (TKI) treatment was more effective in eradicating ALL than treatment with a TKI (nilotinib) alone. Proteomic analysis revealed that α6 deletion in murine ALL was associated with changes in Src signaling, including the upregulation of phosphorylated Lyn (pTyr507) and Fyn (pTyr530). Thus, our data support α6 as a novel therapeutic target for ALL.

Diagnosis and Treatment of Lymphatic Complications of the Groin Following Open Lower Extremity Revascularization with Plastic Surgery Closure.

INTRODUCTION: Lymphatic complications following vascular procedures involving the groin require prompt treatment to limit morbidity. Several treatments have been described, including conservative management, aspiration, sclerotherapy, and direct lymphatic ligation with or without a muscle flap have been described. To date, there is no data indicating which treatment results in the shortest time to recovery. We sought to address this gap by conducting a retrospective cohort study. METHODS: We reviewed all patients who developed a lymphatic complication after undergoing an open revascularization procedure in the groin between 2014 and 2020 in which plastic surgery was involved in the closure. A control group consisted of patients from the same timespan who did not develop a lymphatic complication. Demographics, comorbidities, operative details, and outcomes were compared between these groups. For cases identified with a lymphatic complication, the method of diagnosis, culture data, and treatment details were collected, and outcomes were compared for surgical management versus sclerotherapy. RESULTS: There were 27 lymphatic complications and 60 control patients. The complication group had a higher incidence of aortofemoral bypass (25.8% vs. 8.3%, P = 0.04), and a lower incidence of femoral-to-distal bypass (11.1% vs. 45.0%, P < 0.01). Daily drain output volume from postoperative days 1-5, and days 6-10, was significantly higher in the complication group than in the controls (194.0 vs. 44.0, P < 0.01; and 429.5 vs. 35.0, P < 0.01, respectively). In the lymphatic leak group, 16 patients (59.3%) had surgical treatment and six (22.2%) had sclerotherapy. Of those who had surgery, 71.4% had successful outcomes without the need for an additional intervention, whereas all of the patients analyzed who were treated with sclerotherapy had successful outcomes without further intervention. The average time to resolution was significantly shorter for surgery than for sclerotherapy (38.7 vs. 86.0 days, P = 0.03). CONCLUSIONS: Daily postoperative drain volume can assist with early diagnosis of a lymphatic leak in the groin following an open revascularization procedure. Sclerotherapy and surgery were each successful, but surgery resulted in significantly shorter times to resolution. In the appropriate candidates, surgery should be considered first line management of a lymphatic leak.

Prophylactic Muscle Flaps in Primary Vascular Procedures of the Groin.

BACKGROUND: Complications following vascular procedures involving the groin can lead to significant morbidity. Achieving stable soft tissue coverage over sites of revascularization can help mitigate complications. Prior evidence supports the use of muscle flaps in reoperative groins and in high risk patient populations to reduce postoperative complications. Data regarding the use of prophylactic muscle flap coverage of the groin is lacking. Therefore, the purpose of this study is to evaluate the effect of immediate prophylactic muscle flap coverage of vascular wounds involving the groin. METHODS: A retrospective cohort study was performed on all patients undergoing primary open vascular procedures involving the groin for occlusive, aneurysmal, or oncologic disease between 2014 and 2020 at a single institution where plastic surgery was involved in closure. Patient demographics, comorbidities, surgical details, and postoperative complications were compared between patients who had sartorius muscle flap coverage of the vascular repair versus layered closure alone. RESULTS: A total of 133 consecutive groins were included in our analysis. A sartorius flap was used in 115 groins (86.5%) and a layered closure was used in 18 (13.5%). Wound breakdown was similar between groups (25.2% sartorius vs. 38.9% layered closure, P = 0.26). However, the rate of reoperation was significantly higher in the layered closure group (50.0% vs. 12.2%, P < 0.01). Among patients who experienced wound breakdown (N = 36), a larger proportion of layered closure patients required operative intervention (71.4% vs. 20.7%, P = 0.02). Other rates of complications were not statistically different between groups. CONCLUSIONS: In patients undergoing primary open vascular procedures involving the groin, patients who underwent prophylactic sartorius muscle flap closure had lower rates of reoperation. Although incisional breakdown was similar between the groups overall, the presence of a vascularized muscle flap overlying the vascular repair was associated with reduced need for reoperation and allowed more wounds to be managed with local wound care alone. Consideration should be given to this low morbidity local muscle flap in patients undergoing vascular procedures involving the groin.

Facial Feminization Surgery: Key CT Findings for Preoperative Planning and Postoperative Evaluation.

Facial feminization surgery is an increasingly performed component of gender affirmation surgery for transgender women. Preoperative facial CT is performed to plan the adjustment of the patient's masculine characteristics to feminine and to plan operative navigation around specific readily identifiable anatomic structures. In the upper face, surgery is performed to reduce the prominence of the brow and increase the nasofrontal angle; the radiology report should indicate the frontal sinus and supraorbital foramen anatomy. In the midface, rhinoplasty is performed to increase the nasofrontal and nasolabial angles; the radiology report should indicate the presence of a dorsal hump and septal deviation or spurring. In the lower face, the prominence of the chin and squareness of the jaw are adjusted via genioplasty and mandible contouring, respectively; the radiology report should describe the location and potential anatomic variations of the inferior alveolar nerve and mental foramina as well as the presence of dental abnormalities that directly inform the surgical approach. CT may also be performed if there is clinical suspicion for postoperative complications such as hardware fracture or osteotomy through the supraorbital or mental foramen. Familiarity with these findings will facilitate improved communication between radiologists and surgeons, thereby contributing to the care of transgender women.

Facial Feminization Surgery: Key CT Findings for Preoperative Planning and Postoperative Evaluation.

Facial feminization surgery (FFS) is an increasingly performed component of gender affirmation surgery for transgender women. Preoperative facial CT is performed to plan the adjustment of the patient's masculine characteristics to feminine, and to plan operative navigation around specific readily identifiable anatomic structures. In the upper face, surgery is performed to reduce the prominence of the brow and increase the nasofrontal angle; the radiology report should indicate the frontal sinus and supraorbital foramen anatomy. In the midface, rhinoplasty is performed to increase the nasofrontal and nasolabial angles; the radiology report should indicate presence of a dorsal hump and septal deviation or spurring. In the lower face, prominence of the chin and squareness of the jaw are adjusted via genioplasty and mandible contouring, respectively; the radiology report should describe the location and potential anatomic variations of the inferior alveolar nerve and mental foramina, as well as presence of dental abnormalities that directly inform the surgical approach. CT may also be performed if there is clinical suspicion for postoperative complications such as hardware fraction or osteotomy through the supraorbital or mental foramen. Familiarity with these findings will facilitate improved communication between radiologists and surgeons, thereby contributing to the care of transgender women.

Smoking cessation and receipt of cessation advice from health professionals among older smokers in Taiwan.

OBJECTIVES: To examine the prevalence and correlates of smoking cessation and receiving professional cessation advice among older smokers in Taiwan. METHODS: Cross-sectional data from the 2008-2010 and 2012 Taiwan Adult Smoking Behavior Survey was used to form a sample of 4081 recent active smokers aged 50+, comprising current smokers and former smokers who quit smoking within the past 12months. We examined three outcome variables: quit attempt in the past 12months, successful cessation for at least 3months, and receipt of health professional cessation advice. Multivariate logistic regressions were used to identify significant correlates. RESULTS: During the study period, the annual quit attempt rate was 41.4%, annual successful cessation rate was 4.7%, and prevalence of receiving cession advice among smokers who visited health professionals within the past 12months was 72.3%. After controlling for other covariates, quit attempts were significantly higher in 2009 and positively associated with higher education, poorer health status, smoke-free homes, and receipt of cessation advice. Successful cessation was significantly higher in 2009, positively associated with older age, higher income, and smoke-free homes, and negatively associated with receiving cessation advice. Receipt of cessation advice was significantly lower in 2010 and 2012, positively associated with male gender, older age, and poorer health status, and negatively associated with higher education. CONCLUSIONS: Our results suggest that targeting lower educated and lower income subgroups, adopting effective strategies to increase voluntary smoke-free home rules, and improving professional cessation advice will have great potential to further reduce smoking prevalence in older smokers.

Contemporary diagnostics: sarcoma pathology update.

Sarcoma diagnosis continues to evolve as new information is discovered. Certain tumors have been downgraded (dermal leiomyosarcoma) and an atypical category designed for others. Recently entities include myxoinflammatory fibroblastic sarcoma, myoepithelioma, and pseudomyogenic hemangioendothelioma. The terms malignant fibrous histiocytoma and hemangiopericytoma are outdated. New immunostains (STAT6, SOX10, ERG) add diagnostic specificity, and new risk assessment models are described for sarcomas where grading and staging has failed to provide adequate prognosis.

Recurrent atypical fibroxanthoma with satellite metastasis.

Atypical fibroxanthoma (AFX) is a cutaneous neoplasm of uncertain etiology that develops on sun-exposed regions of elderly males. It is widely considered to act indolently, despite its highly malignant cytologic features. Reports of metastatic AFX are very rare, and recurrence is uncommon. We report a case of recurrent AFX exhibiting a pattern of satellite metastasis followed by evidence of regional lymph node metastasis. A 76-year-old male with prior occupational and therapeutic radiation exposure and numerous squamous cell carcinomas had AFX of the left vertex scalp limited to the dermis completely removed by micrographic surgery. Twenty months later, multiple lesions appeared at the site of previous surgery. Imaging revealed no metastases or calvarial involvement. Wide local excision showed multiple well-defined nodules involving dermis and subcutis. The primary and recurrent neoplasms were similar and composed of pleomorphic epithelioid and spindled cells with marked nuclear atypia, hyperchromasia and mitotic activity. Immunohistochemistry was positive for CD10, procollagen1 and vimentin and negative for cytokeratins AE1/AE3, cytokeratins 5/6, 34ßE12, MNF116, p63 CD31, Mart1, smooth muscle actin, desmin, S100 and CD34. Forty-eight months after removal of the primary, left intraparotid and posterior triangle lymph nodes are suspected to be involved by metastasis using clinical and positron emission tomography/ computed tomography examinations.

Ossifying plexiform tumor.

We report a rare case of ossifying plexiform tumor in a 64-year-old female. The patient had a 2-year history of gradual hardening of the right thumb pad and pain that radiated up the forearm. Physical examination showed a tender, mobile 2-cm subcutaneous nodule distending the tip of the right thumb. The biopsy specimen showed a well-delineated tumor with multiple lobules of epithelioid and spindled cells arranged in a plexiform pattern separated by fibrous bands and having foci of bone formation. The neoplastic cells had scant-to-moderate amphophilic cytoplasm with mild nuclear pleomorphism in a myxocollagenous background. No necrosis, mitoses or cytological atypicia were seen. The osteocytes present in the bone islands were bland, with occasional rimming osteoblasts. X-ray showed stippled calcification in the soft tissue of the distal thumb without involvement of the phalanx. The patient is tumor free for 1 year after complete local excision. Only three cases of ossifying plexiform tumor have been reported. All previous cases and the current case presented as subcutaneous nodules on hand digits of females, measuring 1-2 cm in greatest dimension. Ossifying plexiform tumor appears to be a benign neoplasm with no reports of progression or metastasis.

Prognostic value of breast cancer subtypes, Ki-67 proliferation index, age, and pathologic tumor characteristics on breast cancer survival in Caucasian women.

Estrogen receptor (ER), progesterone receptor (PR), and epidermal growth factor receptor 2 (HER2) status are well-established prognostic markers in breast cancer management. The triple negative breast carcinoma subtype (ER-/PR-/HER2-) has been associated with worse overall prognosis in comparison with other subtypes in study populations consisting of ethnic minorities and young women. We evaluated the prognostic value of breast cancer subtypes, Ki-67 proliferation index (Ki-67PI), and pathologic tumor characteristics on breast cancer survival in Caucasian women in our institution, where greater than 90% of the total patient population is white. From 628 new invasive breast cancer cases in our data base (2000-late 2004), 593 (94%) were identified in Caucasian women. ER/PR/HER2 breast cancer subtypes were classified based on St. Gallen International Expert Consensus recommendations from 2011. ER/PR/HER2 status and its effect on survival were analyzed using a Kaplan-Meier curve. ER/PR/HER2 status, grade, tumor-node-metastasis status (TNM)/anatomic stage, and age were analyzed in terms of survival in a multivariate fashion using a Cox regression. Ki-67PI was analyzed between ER/PR/HER2 groups using the Kruskal-Wallis, Mann-Whitney U-tests, and 2 × 5 ANOVA. Our results showed that patients with stage IIB through stage IV breast carcinomas were 2.1-16 times more likely to die than patients with stages IA-B and IIA disease, respectively (95% CI 1.17-3.81 through 9.68-28.03, respectively), irrespective of ER/PR/HER2 subtype. Similar effect was seen with T2, N2/N3, or M1 tumors in comparison with T1, N0/N1, and M0 tumors. Chances of dying increase approximately 5% for every year increase in age. There was a significant main effect of Ki-67PI between ER/PR/HER2 subtypes, p < .001, but Ki-67PI could not predict survival. In summary, TNM status/anatomic stage of breast carcinomas and age are predictive of survival in our patient population of Caucasian women, but breast carcinoma subtypes and Ki-67 proliferation index are not.

Mutational derivatives of PhiC31 integrase with increased efficiency and specificity.

phiC31 integrase is a sequence-specific phage recombinase that can recombine two short DNA sequences called attB and attP. The enzyme can also promote genomic integration of plasmids carrying attB into native mammalian sequences having partial identity to attP. To increase the efficiency of integration, we mutated the phiC31 integrase gene and screened the mutants in human cells in an assay for higher recombination frequency between attB and attP. We report in this article the isolation of a mutant, P2 that has twice the chromosomal integration frequency of wild-type phiC31 integrase, at both a preintegrated chromosomal attP site and at endogenous pseudo attP sequences in cultured human cells. In mouse liver, P2-mediated integration provided therapeutic long-term levels of human factor IX that were double those generated by wild-type phiC31 integrase. We also describe an additional mutant, P3 that combines the mutations of P2 with further changes and possesses an elevated specificity for integration at a chromosomally placed attP site in human cells. Forty-four percent of colonies carrying integration events mediated by P3 have integration at the placed attP site. These mutant integrases are useful for gene therapy and genome modification, and they demonstrate the feasibility of engineering phiC31 integrase toward more desirable properties.

Human ARF Specifically Inhibits Epimorphic Regeneration in the Zebrafish Heart.

The Alternative Reading Frame (ARF) protein is a tumor suppressor encoded by the Cyclin Dependent Kinase Inhibitor 2A gene in mammals but not lower regenerative vertebrates, and has been previously implicated as a context-sensitive suppressor of regeneration in murine skeletal muscle and humanized ARF-expressing zebrafish fins. This study extends our investigation of the role of ARF in the regeneration of other solid tissues, including the zebrafish heart and the mammalian digit. Heart regeneration after cryoinjury was used to mimic massive myocardial infarction. ARF gene expression was upregulated during the cardiac regenerative process and slowed the rate of morphological recovery. ARF specifically impacts cardiomyocytes, neovascularization, and the endothelial-mesenchymal transition, while not affecting epicardial proliferation. This suggests that in the context of regeneration, ARF is specifically expressed in cells undergoing dedifferentiation. To investigate ARF as a suppressor of epimorphic regeneration in mammalian systems, we also tested whether the absence of ARF was permissive for murine digit regeneration, but found that ARF absence alone was insufficient to significantly alter digit restoration. These findings provide additional evidence that ARF suppresses epimorphic regeneration, but suggests that modulation of ARF alone is insufficient to permit regeneration.

Functionally heterogeneous human satellite cells identified by single cell RNA sequencing.

Although heterogeneity is recognized within the murine satellite cell pool, a comprehensive understanding of distinct subpopulations and their functional relevance in human satellite cells is lacking. We used a combination of single cell RNA sequencing and flow cytometry to identify, distinguish, and physically separate novel subpopulations of human PAX7+ satellite cells (Hu-MuSCs) from normal muscles. We found that, although relatively homogeneous compared to activated satellite cells and committed progenitors, the Hu-MuSC pool contains clusters of transcriptionally distinct cells with consistency across human individuals. New surface marker combinations were enriched in transcriptional subclusters, including a subpopulation of Hu-MuSCs marked by CXCR4/CD29/CD56/CAV1 (CAV1+). In vitro, CAV1+ Hu-MuSCs are morphologically distinct, and characterized by resistance to activation compared to CAV1- Hu-MuSCs. In vivo, CAV1+ Hu-MuSCs demonstrated increased engraftment after transplantation. Our findings provide a comprehensive transcriptional view of normal Hu-MuSCs and describe new heterogeneity, enabling separation of functionally distinct human satellite cell subpopulations.

Muscle stem cell activation in a mouse model of rotator cuff injury.

Rotator cuff (RC) tears are frequently complicated by muscle atrophy. Muscle stem cells (MuSCs) repair damaged myofibers following injury, but their role in the prevention or pathogenesis of atrophy following RC tears remains undefined. We hypothesized that the RC MuSC population would be affected by supraspinatus (SS) and infraspinatus (IS) tendon transection (TT) compared to uninjured muscle in a mouse model of RC tear. C57BL6/J mice underwent unilateral SS and IS TT and contralateral sham surgery. At 3, 8, or 14 weeks after injury, mice were euthanized, and SS and IS were harvested for FACS sorting of CD31-/CD45-/Sca1-/ITGa7+/VCAM+ MuSCs or histological analysis. Ki-67+ MuSCs from injured muscle increased 3.4-fold at 3 weeks (p = 0.03) and 8.1-fold at 8 weeks (p = 0.04) following TT injury, but returned to baseline by 14 weeks (p = 0.91). Myod1 remained upregulated 3.3-fold at 3 weeks (p = 0.03) and 2.0-fold at 14 weeks (p = 0.0003), respectively. Myofiber cross-sectional area was decreased at both 3 and 14 weeks after injury, but the number of MuSCs per fiber remained relatively constant at 3 (p = 0.3) and 14 (p = 0.6) weeks after TT. In this study, we characterized the longitudinal effect of RC tendon injury on the MuSC population in supraspinatus and infraspinatus muscles. MuSCs are transiently activated, and are not depleted, in spite of persistent muscle atrophy. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1370-1376, 2018.

High-Yield Purification, Preservation, and Serial Transplantation of Human Satellite Cells.

Investigation of human muscle regeneration requires robust methods to purify and transplant muscle stem and progenitor cells that collectively constitute the human satellite cell (HuSC) pool. Existing approaches have yet to make HuSCs widely accessible for researchers, and as a result human muscle stem cell research has advanced slowly. Here, we describe a robust and predictable HuSC purification process that is effective for each human skeletal muscle tested and the development of storage protocols and transplantation models in dystrophin-deficient and wild-type recipients. Enzymatic digestion, magnetic column depletion, and 6-marker flow-cytometric purification enable separation of 104 highly enriched HuSCs per gram of muscle. Cryostorage of HuSCs preserves viability, phenotype, and transplantation potential. Development of enhanced and species-specific transplantation protocols enabled serial HuSC xenotransplantation and recovery. These protocols and models provide an accessible system for basic and translational investigation and clinical development of HuSCs.

The PI3Kδ Inhibitor Idelalisib Inhibits Homing in an in Vitro and in Vivo Model of B ALL.

The quest continues for targeted therapies to reduce the morbidity of chemotherapy and to improve the response of resistant leukemia. Adhesion of acute lymphoblastic leukemia (ALL) cells to bone marrow stromal cells triggers intracellular signals that promote cell-adhesion-mediated drug resistance (CAM-DR). Idelalisib, an U.S. Food and Drug Administration (FDA)-approved PI3Kδ-specific inhibitor has been shown to be effective in CLL in down-regulating p-Akt and prolonging survival in combination with Rituximab; herein we explore the possibility of its use in B ALL and probe the mechanism of action. Primary B ALL in contact with OP9 stromal cells showed increased p-Aktser473. Idelalisib decreased p-Akt in patient samples of ALL with diverse genetic lesions. Addition of idelalisib to vincristine inhibited proliferation when compared to vincristine monotherapy in a subset of samples tested. Idelalisib inhibited ALL migration to SDF-1α in vitro and blocked homing of ALL cells to the bone marrow in vivo. This report tests PI3Kδ inhibitors in a more diverse group of ALL than has been previously reported and is the first published report of idelalisib inhibiting homing of ALL cells to bone marrow. Our data support further pre-clinical evaluation of idelalisib for the therapy of B ALL.

Long-term increase in mVEGF164 in mouse hindlimb muscle mediated by phage phiC31 integrase after nonviral DNA delivery.

Peripheral vascular disease (PVD), characterized by insufficient blood supply to extremities, can be a devastating illness. Although many gene therapy strategies for PVD using vascular endothelial growth factor (VEGF) have resulted in increased blood vessel formation, the vessels are often impermanent and regress after therapy, probably because of the short-lived VEGF expression mediated by gene therapy vectors (14 days or less). phiC31 integrase is a recombinase originally isolated from a bacteriophage of Streptomyces. This integrase performs efficient chromosomal integration of plasmid DNA into mammalian genomes that results in long-term transgene expression. In this study, gene transfer was achieved by intramuscular injection of VEGF and integrase plasmid DNAs into the tibialis anterior muscle in the mouse hindlimb, followed by electroporation of the muscle with needle electrodes. We observed VEGF levels significantly above background 40 days after injection in animals that received phiC31 integrase and the VEGF plasmid. Site-specific integration of plasmid DNA in the chromosomes of muscle tissue was verified by polymerase chain reaction at a common integration site. These results suggest the possible utility of the phiC31 integrase system to treat ischemic disease.

Postoperative Prophylactic Antibiotic Use following Ventral Hernia Repair with Placement of Surgical Drains Reduces the Postoperative Surgical-Site Infection Rate.

BACKGROUND: To help prevent complications after incisional ventral hernia repair, traditional teaching has recommended using closed suction drains. However, some studies suggest that there is an increased infection risk with use of surgical drains, and it is uncertain whether use of extended postoperative prophylactic antibiotics while drains remain in place helps prevent surgical-site infections. Evidence guiding surgeons' clinical practice regarding antibiotic use following hernia repair is lacking. METHODS: The authors sought to determine whether the use of extended postoperative antibiotic prophylaxis beyond standard Surgical Care Improvement Project guidelines with closed-suction surgical drain placement in incisional ventral hernia repair reduces the incidence of postoperative surgical-site infections. A retrospective review of 234 patients who underwent an incisional ventral hernia repair from 2003 to 2013 at a single institution was performed. Demographic, preoperative, operative, and postoperative data were collected and analyzed. RESULTS: Extended postoperative prophylactic antibiotics significantly reduce the incidence of postoperative surgical-site infections (OR, 0.31; p < 0.01). The odds ratio, when stratified by Ventral Hernia Working Group Scale, was 0.63, 0.25, 0.30, and 0.13 (p < 0.001 by the Mantel-Haenszel combined test) for grades 1, 2, 3, and 4, respectively, but was not statistically significant for differences between hernia grades. However, as the hernia grade increased, the odds ratio tended to decrease, suggesting that extended prophylactic antibiotics may be more effective at decreasing the incidence of surgical-site infections at higher grades. CONCLUSION: Extended antibiotic prophylaxis reduces surgical site infection risk following complex ventral hernia repairs, and should be considered in all cases. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Phyllodes tumor of vulva: a brief diagnostic review.

Phyllodes tumors of the vulva are rare proliferations that share morphologic similarities with breast neoplasms. Their histogenetic origin is elusive and may be associated with specialized mammary-like glands of the vulva. Because of their rarity, the clinical and pathologic features, classification, and therapy are not well defined, and their biologic behavior is difficult to predict by histology alone. Immunohistochemical expression of estrogen and progesterone receptors and breast markers provide further support for a common origin. Surgical resection is the current mainstay of therapy and is definitive in most cases.

Photoletter to the editor: Diffuse cocaine-related purpura.

Diffuse purpura is an uncommon skin manifestation found in platelet and coagulation disorders, meningococcemia, vasculitides and cocaine use. Reports of cocaine-related purpura predominantly involve adulteration with the anti-helminthic, levamisole. Levamisole enhances the effects of cocaine and is known to cause vasculitis. Recently, the CDC also released an advisory of oxymorphone being used intravenously causing thrombogenic thrombocytopenic purpura (TTP). We report the case of a patient with diffuse purpura ultimately diagnosed with cocaine-related thrombogenic vasculopathy. In the current environment of adulterated cocaine usage and increased prescription narcotic abuse, it is crucial to investigate substance abuse as a cause of diffuse purpura.