Arm Lesions Research Articles

Superficial angiomyxoma-like myxofibrosarcoma

Abstract Introduction/Objective Myxofibrosarcoma comprises a spectrum of malignant fibroblastic neoplasms with variably myxoid stroma, pleomorphism, and a distinctive curvilinear vascular pattern. Herein we describe a case of myxofibrosarcoma with unusual histological features that could be deceptive, mimic superficial angiomyxoma and make the diagnosis challenging Methods/Case Report A 74-year-old female presented with a right upper arm lesion that had been present for 10-12 months and had significantly increased in size over this time and became painful. There was no history of trauma. Examination demonstrated approximately 3 cm multinodular mass along the anterior aspect of the proximal arm. There were no overlying skin discolorations or ecchymosis. The patient underwent a shave biopsy and then resection. Grossly, the lesion was gray-white firm with an ill-defined border covered with a tan-white skin ellipse. Histologically, the lesion was located in the dermis extending to the dermal-epidermal junction. The lesion comprised mainly of myxoid stroma, arborizing, and plexiform thin-walled blood vessels, stellate to spindled cells with enlarged hyperchromatic nuclei, and eosinophilic cytoplasm in addition to the presence of stromal neutrophils and hyperplastic overlying squamous epithelium. The morphologic appearance elicited the differential diagnosis of superficial angiomyxoma and low-grade myxofibrosarcoma. While many features were more suggestive of superficial angiomyxoma, the degree of atypia and mitotic activity (12/10 HPF) was outside the realm of angiomyxoma and warranted the diagnosis of myxofibrosarcoma Results (if a Case Study enter NA) NA Conclusion Although rare, myxofibrosarcoma may rarely extend to the dermal-epidermal junction and mimic superficial angiomyxoma. The presence of cytologic atypia and increased mitotic activity favors myxofibrosarcoma

Effect of Microdoses of Incisional Antibiotics on the Rate of Surgical Site Infections in Skin Cancer Surgery

Surgical site infections (SSIs) represent a costly and preventable complication of cutaneous surgery. However, there is a paucity of randomized clinical trials investigating antibiotic prophylaxis for reducing SSIs in skin cancer surgery, and evidence-based guidelines are lacking. Incisional antibiotics have been shown to reduce the rate of SSIs before Mohs micrographic surgery, but this represents a small subset of skin cancer surgery. To determine whether microdosed incisional antibiotics reduce the rate of SSIs before skin cancer surgery. In this double-blind, controlled, parallel-design randomized clinical trial, adult patients presenting to a high-volume skin cancer treatment center in Auckland, New Zealand, for any form of skin cancer surgery over 6 months from February to July 2019 were included. Patient presentations were randomized to one of 3 treatment arms. Data were analyzed from October 2021 to February 2022. Patients received an incision site injection of buffered local anesthetic alone (control), buffered local anesthetic with microdosed flucloxacillin (500 µg/mL), or buffered local anesthetic with microdosed clindamycin (500 µg/mL). The primary end point was the rate of postoperative SSI (calculated as number of lesions with SSI per total number of lesions in the group), defined as a standardized postoperative wound infection score of 5 or more. A total of 681 patients (721 total presentations; 1133 total lesions) returned for postoperative assessments and were analyzed. Of these, 413 (60.6%) were male, and the mean (SD) age was 70.4 (14.8) years. Based on treatment received, the proportion of lesions exhibiting a postoperative wound infection score of 5 or greater was 5.7% (22 of 388) in the control arm, 5.3% (17 of 323) in the flucloxacillin arm, and 2.1% (9 of 422) in the clindamycin arm (P = .01 for clindamycin vs control). Findings were similar after adjusting for baseline differences among arms. Compared with lesions in the control arm (31 of 388 [8.0%]), significantly fewer lesions in the clindamycin arm (9 of 422 [2.1%]; P < .001) and flucloxacillin (13 of 323 [4.0%]; P = .03) arms required postoperative systemic antibiotics. This study evaluated the use of incisional antibiotics for SSI prophylaxis in general skin cancer surgery and compared the efficacy of flucloxacillin vs clindamycin relative to control in cutaneous surgery. The significant reduction in SSI with locally applied microdosed incisional clindamycin provides robust evidence to inform treatment guidelines in this area, which are currently lacking. anzctr.org.au Identifier: ACTRN12616000364471.

Kimura's disease: A clinicopathological study of 23 cases.

Kimura's disease (KD) is an uncommon lymphoproliferative fibroinflammatory disorder. Patients present with head and neck subcutaneous nodules with or without lymphadenopathy. Peripheral blood eosinophilia and elevated serum immunoglobulin E (IgE) levels are typical. This study was designed to delineate the clinicopathological features, pattern of care, and disease course of 23 Taiwanese patients with KD. We retrospectively analyzed the clinical data of 23 consecutive cases (16 male and 7 female; age at diagnosis: 12-77 years) of KD diagnosed at our institution from 2015 to 2020. The median time from presentation to diagnosis was 1 month. Twenty-one patients presented with unilateral or bilateral head and neck masses. The remaining two presented with right flank and right arm lesions, respectively. Peripheral blood eosinophilia was observed in nine, and elevated IgE levels were observed in four. All were diagnosed using either excisional or core-needle biopsy. Seven patients underwent fine needle aspiration without a diagnostic yield. Salivary gland and lymph node involvement was observed in three and seven patients, respectively. Most lesions showed tissue eosinophilia (100%) and florid follicular hyperplasia (78.26%). Three cases had histological KD-IgG4-RD overlap and three had comorbid IgG4-RD were recognized. Thirteen patients underwent surgical resection, one received adjuvant therapy, and two received prednisolone monotherapy. KD should be considered in patients with subcutaneous masses, eosinophilia, and elevated IgE levels. Biopsy remains the gold standard of diagnosis. Increased recruitment of IgG4+ plasma cells is a common feature. Consideration of IgG4-RD in all KD patients may be prudent.

1171. Epidemiology of Old World Cutaneous Leishmaniasis among Members of the U.S. Military

Abstract Background Cutaneous leishmaniasis (CL) is a threat to U.S. Military personnel as they deploy to endemic areas. As treatment may require evacuation, CL undermines operations. Elucidating the epidemiology of CL in this population is key for prevention. Methods We retrospectively reviewed data from a CL sodium stibogluconate treatment trial at Walter Reed Army Medical Center, Washington DC. 412 military members with parasitologically confirmed CL and deployment to Southwest Asia from May 2002 - August 2004 enrolled. Subjects’ CL lesions were counted and measured. 334 subjects completed a risk survey. Given no control group, we used number of CL lesions (NL), total lesion area (TLA), and lesion location as outcomes to assess CL risks. Non-parametric tests and logistic regression were used as appropriate. Results Permethrin treated bed net use was associated with lower NL (p = 0.000), TLA (p = 0.024), and odds of head/face lesion (OR 0.12, p = 0.047). Sleeping in a combat uniform was associated with lower TLA (p = 0.000) and odds of leg/foot lesion (OR 0.39, p = 0.023). Use of a permethrin treated uniform (p = 0.002) and N,N-diethyl-meta-toluamide (DEET) insect repellent at night (p = 0.046) were associated with lower NL. Noting unit members with similar lesions was associated with higher NL (p = 0.007) and odds of head/face lesion (OR 12.1, p = 0.019). National Guard status followed by Active Duty was associated with higher NL (p = 0.002) and TLA (p = 0.000) than Reserve. Sleeping in a building was associated with higher TLA (p = 0.008) and odds of arm lesion (OR 2.28, p = 0.016). Sleeping near animal burrows was associated with higher NL (p = 0.031). Sleeping on a cot (p = 0.006), certain ethnicities (p = 0.020) and certain military occupational specialties (p =0.038) were associated with higher TLA. Increasing age (p = 0.001) and years of service (p = 0.000) were positively correlated with TLA. Conclusion This is the largest group of U.S. Military members with CL reported and provides insight into risks for CL which will guide preventive efforts to reduce the burden of illness in this population. The opinions and assertions expressed herein are those of the author(s) and do not reflect the official policy or position of the Uniformed Services University of the Health Sciences, the Department of Defense, or the U.S. Government. Disclosures Naomi E. Aronson, M.D., Elsevier: Royalties as text editor, honoraria for chapter writing|UpToDate: royalties for writing chapters.

Prophylactic Radiation Therapy vs. Standard-of-Care for Patients with High-Risk, Asymptomatic Bone Metastases: A Multicenter, Randomized Phase II Trial

<h3>Purpose/Objective(s)</h3> External beam radiotherapy (RT) is standard-of-care (SOC) for pain relief of symptomatic bone metastases. We aimed to test whether radiation for asymptomatic bone metastases prevents skeletal-related events (SRE). <h3>Materials/Methods</h3> We conducted a multicenter, randomized phase 2 trial (NCT03523351) of prophylactic RT to high-risk, asymptomatic bone metastases vs SOC. Patients were eligible if they were at least 18 years old with a metastatic solid tumor malignancy and more than 5 metastatic lesions, including at least one asymptomatic high-risk bone lesion, defined as: bulky disease (≥2cm in longest diameter), junctional spine or posterior spinal element disease, disease involving hip or sacroiliac joint, or disease in long bone involving 1/3-2/3 cortical thickness. Patients were stratified by histology and planned SOC (systemic therapy or observation) and randomly assigned in a 1:1 ratio to RT to all enrolled high-risk bone metastases or SOC alone. The primary outcome of SRE (defined as fracture, cord compression, or intervention with surgery or radiation) was analyzed from randomization to death or 12 months. A sample size of 66 was deemed necessary to achieve 80% power to detect a difference of 30% (experimental arm) versus 60% (SOC arm) using a two-sample, one-sided proportion test with alpha<0.05. We used the log-rank test for time-to-event analyses and Wilcoxon rank sum test to compare hospitalizations, brief pain inventory and quality of life (using EQ-5D-5L) between arms. <h3>Results</h3> Between May 8, 2018 and August 9, 2021, 78 patients with 122 bone metastases were enrolled and randomized to prophylactic RT (n=39) or SOC (n=39). The most common primary cancer types were lung (27%), breast (24%), and prostate (22%). Seventy-one patients (91%) were evaluable for the primary endpoint. At one year, SRE occurred in 1 of 62 lesions (1.6%) in the RT arm and 14 of 49 lesions (29%) in the SOC arm (p<0.001). There was a significant difference in time-to-SRE by type of high-risk feature (p=0.016), with most events occurring in junctional spine and bulky disease. There were significantly fewer patients hospitalized for SRE in the RT arm compared to the SOC arm (4 vs 0, p=0.045). At a median follow-up of 2.4 years, overall survival was significantly longer in the RT arm (HR 0.50, 95% CI 0.28, 0.91; p=0.02). Median OS among 11 patients with an SRE was 1.1 years compared to 1.5 years among 67 patients without an SRE. Pain was reduced at 3 months in the RT arm (p<0.05) compared to the SOC arm. EQ-5D-5L was similar between the groups at all time points. <h3>Conclusion</h3> Radiation delivered prophylactically to asymptomatic, high-risk bone metastases reduced skeletal-related events, meeting the primary endpoint of the study. Importantly, we observed an improvement in overall survival, with potential mechanisms of palliation or debulking warranting further investigation in a phase 3 trial.

Comparative study of the efficacy of fractional Er: YAG 2940 nm laser and Q-switched Nd: YAG 1064 nm laser in keratosis pilaris.

Keratosis pilaris is a common keratinization disorder of the extensor surfaces of the proximal extremities. Various treatment modalities reduce symptoms, but their efficacy is limited. The aim of this study is to compare the efficiency of Q-Switched Nd: YAG laser and fractional Er: YAG laser. The lesions in both arms were randomly divided into areas A and B. Fractional Er: YAG 2940 nm laser performed to area A 1.5J/cm2 , spot size 7 mm, frequency 3Hz and three passes and Q-Switched Nd: YAG 1064 nm laser performed to Area B, 4-6J/cm2 spot size 4 mm, 8Hz frequency, and as a single pass. Both lasers were performed in 4 sessions at 3-week intervals. The global improvement scale evaluated treatment responses in dyspigmentation and skin texture. Twenty patients completed the study, and the mean age of a total of 20 patients was 22.9. There was no significant difference in dyspigmentation and skin texture with global improvement scale between Area A and Area B, respectively (p=0.078, p=0.638). In addition, there was no significant difference between patient satisfaction levels after treatment in Area A and Area B (p=0.868). The efficiency of the fractional Er: YAG 2940 nm laser was found equal to the Q-switched Nd: YAG 1064 nm laser. Fractional Er: YAG 2940 nm laser may be a new treatment option in the treatment of keratosis pilaris.

Clinical utility of purgative bowel preparation before capsule endoscopy: a multicenter, blinded, randomized controlled trial

Optimal bowel preparation before capsule endoscopy (CE) is currently unknown. In this multicenter, blinded, randomized controlled trial, we assessed clinical effectiveness of 2 types of purgative regimen and a control arm of clear fluid only. Patients with suspected small intestinal bleeding were randomized into 3 arms: arm A, clear fluids only for 18 hours before CE and simethicone 200 mg in 150 mL water immediately before CE; arm B, same as A+ 2 L of polyethylene glycol (PEG) 12 hours before CE; and arm C, same as A+ 1 L PEG+ sodium ascorbate 3 hours before CE. To assess diagnostic yield, lesions were classified either as highly relevant (P2) or less relevant (P0 or P1) lesions. Small-bowel visualization quality (SBVQ) was assessed using the Brotz score. Patient tolerability was assessed using the visual analog scale (0-10, with lower scores indicating better tolerability). Two hundred twenty-nine patients completed the study. The mean age was 58.7 years (95% confidence interval, 29.3-87.9), and 47.2% were men. There was no significant difference in diagnosis of P2 lesions in arms A, B, and C (48.7%, 48.0%, and 45.9%, respectively; P= .94). Overall SBVQ and distal SBVQ were similar across the 3 arms (P= .94 and P= .68, respectively). Patients reported better tolerability in arm A (mean score, 1.5) compared with arms B and C (mean score, 3.5 and 2.6, respectively; P< .001). The use of a purgative bowel preparation before CE does not improve diagnostic yield or small-bowel visualization and is associated with lower patient tolerance. (Clinical trial registration number: ACTRN 12614000883617.).

Idiopathic Lobular Panniculitis with Extensive Hypermetabolic Lesions in FDG PET-CT Scan: Case Report

Panniculitis indicates ‘inflammation of fat tissue’. Idiopathic Lobular Panniculitis is a rare condition in which inflammation occurs in the subcutaneous tissue, just beneath the skin. It is predominantly observed in women in the age group of 30-60 years. Occasionally, children may also be affected. We report a case of a 57 years old woman, who presented with multiple palpable skin lesions in both thigh, upper arms, breast and facial site specially left cheek and submandibular area. All of her laboratory findings including hematological and biochemical parameters were normal except slightly low white blood cell count. 18FDG PET-CT revealed multiple hypermetabolic lesions in the subcutaneous layer of skin and fat layers of the retroperitoneum. Diagnosis was confirmed by surgical biopsy which was reported as lobular panniculitis. Distinguishing true malignant cutaneous and subcutaneous benign might be difficult, but when lesions show high uptake of FDG, it can be related to an active inflammation. Extensive FDG uptake in a benign case like this is rare. Therefore, 18FDG PET-CT is not only helpful in detecting panniculitis but also feasible for identifying active state of the disease. Bangladesh J. Nuclear Med. 24(1&amp;2): 57-59, 2021

Tyrosine kinase inhibitors for the treatment of indolent systemic mastocytosis: Are we there yet?

Indolent systemic mastocytosis (ISM) is the most prevalent form of systemic mastocytosis. Many patients with ISM suffer from mast cell (MC) mediator-related symptoms. In a small number of patients, hematologic progression is seen in the follow-up. In some patients with ISM, symptoms arising from MC-derived mediators including gastrointestinal symptoms, anaphylaxis, and neuropsychiatric symptoms are kept under control with conventional mediator-targeting drugs or MC-stabilizing agents. However, in a substantial number of patients, the symptoms are refractory to such conventional therapy. For these patients, novel drugs and targeted approaches are considered. One reasonable approach may be to apply tyrosine kinase inhibitors directed against KIT and other key kinase targets expressed in neoplastic MCs in ISM. Because MCs in more than 90% of all patients with typical ISM display the KIT D816V mutant receptor, clinically effective KIT-targeting drugs have to be active against this mutant form of KIT. The 2 such most effective and well-studied agents currently available are midostaurin and avapritinib. Other KIT-targeting drugs, such as imatinib or masitinib, are less effective or even noneffective against KIT D816V and are thus recommended for use only in patients with other KIT mutant forms (noncodon 816 mutations) or with wild-type KIT. In the present article, we review the current state in the treatment of ISM with tyrosine kinase inhibitors, with special emphasis on treatment responses and potential adverse effects. In fact, all of these agents also have unique and common adverse effects, and their use to treat patients with ISM should be balanced against their toxicity and short- and long-term safety.

The Impact of Tumor Treating Fields on Glioblastoma Progression Patterns

Tumor-treating fields (TTFields) are an antimitotic treatment modality that interfere with glioblastoma (GBM) cell division and organelle assembly by delivering low-intensity, alternating electric fields to the tumor. A previous analysis from the pivotal EF-14 trial demonstrated a clear correlation between TTFields dose density at the tumor bed and survival in patients treated with TTFields. This study tests the hypothesis that the antimitotic effects of TTFields result in measurable changes in the location and patterns of progression of newly diagnosed GBM. Magnetic resonance images of 428 newly diagnosed GBM patients who participated in the pivotal EF-14 trial were reviewed, and the rates at which distant progression occurred in the TTFields treatment and control arm were compared. Realistic head models of 252 TTFields-treated patients were created, and TTFields intensity distributions were calculated using a finite element method. The TTFields dose was calculated within regions of the tumor bed and normal brain, and its relationship with progression was determined. Distant progression was frequently observed in the TTFields-treated arm, and distant lesions in the TTFields-treated arm appeared at greater distances from the primary lesion than in the control arm. Distant progression correlated with improved clinical outcome in the TTFields patients, with no such correlation observed in the controls. Areas of normal brain that remained normal were exposed to higher TTFields doses compared with normal brain that subsequently exhibited neoplastic progression. Additionally, the average dose to areas of the enhancing tumor that returned to normal was significantly higher than in the areas of the normal brain that progressed to enhancing tumor. There was a direct correlation between TTFields dose distribution and tumor response, confirming the therapeutic activity of TTFields and the rationale for optimizing array placement to maximize the TTFields dose in areas at highest risk of progression, as well as array layout adaptation after progression.

Biphasic Sarcomatoid Sweat Gland Carcinoma With Ductal Epithelial And Spindled Myoepithelial Cell Components (Malignant Mixed Tumor Of Skin)

Abstract Introduction/Objective Sweat gland carcinomas are a group of malignant skin adnexal tumors that are difficult to diagnose due to their rarity, wide morphologic variation, and limited literature on diagnosis and classification. These tumors may appear bland and morphologically resemble benign skin adnexal tumors, or may appear poorly differentiated and mimic metastatic carcinoma especially from a breast primary. Biphasic sweat gland carcinomas are an even rarer entity, with only few cases reported in literature, and have been described to consist of a well- differentiated ductal epithelial component and a poorly differentiated, sarcomatoid, spindle cell component. Methods/Case Report Our case report describes a 53 year old female referred to our institution for diagnosis of an excised skin lesion of the right upper arm, which had been slowly growing for 8 years. The histology revealed a biphasic malignant neoplasm involving the dermis and subcutis. The tumor consisted of an epithelial cell component with glandular and squamoid morphology and positive for CK5/6, CK7, and CAM5.2, and a spindled myoepithelial cell component with sarcomatoid morphology and positive for S100, vimentin, and p63. Stains for CK20, ER, PR, PAX8, CEA, and TTF1 were negative. The histological and clinical findings favored a primary skin adnexal tumor, rather than a metastatic lesion. The patient underwent wide local excision of the lesion given that margins of the original excision were indeterminate. The histology of this re-excision demonstrated the same biphasic tumor with ductal epithelial and sarcomatoid myoepithelial cell components positive for the same stains. Although margins were negative in this re-excision, 3-4 months later, the patient developed dyspnea with multiple new pulmonary and hilar masses discovered on imaging, and new-onset headache with a frontal lobe mass discovered on brain imaging. These masses were biopsied/resected, and revealed to be metastases of the original cutaneous tumor positive for the same markers. Results (if a Case Study enter NA) NA Conclusion This case report describes a rare, diagnostically challenging case of a biphasic sweat gland carcinoma with ductal epithelial and sarcomatoid myoepithelial cell components, which demonstrated aggressive behavior with distant metastasis. These tumors are a clinicopathological quandary given their rarity and the paucity of literature on their characterization.

NOTHING TO HIDE UP YOUR SLEEVE: A RARE PRESENTATION OF DISSEMINATED NOCARDIOSIS

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Nocardia is a unique member of the order, Actinomycetales. It is a gram-positive, aerobic bacteria that is characterized by its filamentous branching that stains acid-fast. It can be found in soil and decaying vegetation, with inhalation of airborne particles being the most common mode of inoculation. Considered to be a rare, opportunistic infection, the incidence rate is approximately 500-1000 cases in the US per year (1). Although it typically leads to cutaneous disease, Nocardia has the ability to disseminate as widespread disease leading to pulmonary and CNS involvement. CASE PRESENTATION: An 81 year old African-American female with a past medical history of non-Hodgkin Lymphoma treated with radiation in 1999, hypertension, diabetes, hypothyroidism, chronic kidney disease, and heart failure with preserved ejection fraction. She presented with worsening dyspnea, orthopnea, and lower extremity swelling and was admitted for heart failure exacerbation. She was found to have multiple, painful skin abscesses. On presentation, she was septic: febrile and tachycardic with profound leukocytosis. Radiographic imaging revealed multiple, large, cystic fluid collections in the neck, bilateral arms, and left leg along with right, hilar lymphadenopathy and apical cavitary lesion in the right lung. There was a large, anterior chest wall mass communicating with the left arm lesion. IR guided biopsy ruled-out malignancy. General surgery performed I&D's of the peripheral lesions whereas Cardiothoracic Surgery performed I&D of the chest wall mass. Aerobic cultures grew gram-positive, branching bacilli that later speciated to Nocardia pneumoniae. DISCUSSION: The patient was diagnosed with Disseminated Nocardiosis with lymphocutaneous and pulmonary involvement. Our work-up was negative for CNS or bone disease. The exact etiology was unclear. She did not endorse direct trauma/inoculation at lesion sites and denied any unusual exposure to soil, decaying vegetation, or aquatic environments. Despite Nocardia's prevalence in immunocompromised hosts, our patient was determined to be immunocompetent. Fortunately, there was no evidence of recurrence of malignancy and she was HIV negative. Her treatment regimen consisted of a dual agent induction therapy for 6 weeks that was followed by a 6 month maintenance period with a single agent. However, Nocardia has a propensity to recur or progress despite appropriate antibiotic therapy and source control. CONCLUSIONS: Nocardiosis has been described as an emerging infectious disease given the higher number of HIV and transplant patients. Notably, Nocardia pneumoniae is not accounted for in 82 percent of US strains isolated between 1995 and 2004 (2). This species was first described in 2004 with either "undetermined clinical significance" versus "pulmonary disease" (3). This would be a novel presentation of disseminated Nocardia pneumoniae in an immunocompetent host. REFERENCE #1: Rawat D, Rajasurya V, Chakraborty RK, et al. Nocardiosis. [Updated 2020 Aug 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK526075/ REFERENCE #2: Uhde KB, Pathak S, McCullum I Jr, et al. Antimicrobial-resistant nocardia isolates, United States, 1995-2004. Clin Infect Dis 2010; 51:1445. REFERENCE #3: The Complexities of Nocardia Taxonomy and IdentificationPatricia S. Conville, Barbara A. Brown-Elliott, Terry Smith, Adrian M. ZelaznyJournal of Clinical Microbiology Dec 2017, 56 (1) e01419-17; DOI: 10.1128/JCM.01419-17 DISCLOSURES: No relevant relationships by HUY NONG, source=Web Response No relevant relationships by Michael Vu, source=Web Response

Abstract CT217: Phase I, first-in-human trial evaluating BI 1387446 (STING agonist) alone and in combination with ezabenlimab (BI 754091; anti-PD-1) in solid tumors

Abstract Background/Purpose Activation of the stimulator of interferon genes (STING) pathway in intratumoral immune cells leads to increased type I interferon production, promoting recruitment and priming of T-cells against tumor antigens and triggering anti-tumor activity. In patients with cancer, STING agonists have shown clinical activity, with effects increased when combined with an anti-programmed cell death [PD]-1 antibody. BI 1387446 potently and highly selectively activates the STING pathway; ezabenlimab (BI 754091) is a humanized IgG4 anti-PD-1 monoclonal antibody. Tumor regression and enhanced activity of anti-PD-1 therapy was observed after BI 1387446 administration in syngeneic tumor models. Methods NCT04147234 is a first-in-human, Phase I, open-label, multicenter trial of BI 1387446 recruiting a planned 122 patients from six sites across Europe and the USA. Patients will have advanced, unresectable and/or metastatic solid tumors. The main objectives are to characterize safety and determine the maximum tolerated dose (MTD) of BI 1387446 alone and in combination with ezabenlimab. BI 1387446 will be administered intratumorally at escalating doses as monotherapy in Arm A (~34 patients), and + ezabenlimab (240 mg every 3 weeks, IV) in Arm B (~44 patients); BI 1387446 will be administered in superficial lesions in both Arms. In a potential Arm C (~44 patients), BI 1387446 will be administered in deep/visceral lesions + ezabenlimab, IV. Arm B will open at the starting dose level once the starting dose level in Arm A is considered safe by the safety monitoring committee; Arm C may open at the starting dose level once this dose level is considered safe in Arm B. Dose escalation will be guided by a Bayesian Logistic Regression Model with overdose control. Patients (≥18 years of age) must have exhausted standard treatment options, have ≥1 tumor lesion suitable for injection, ≥1 additional tumor lesion amenable to biopsy, and ECOG performance status ≤1. Treatment will continue until progressive disease, unacceptable toxicity, other withdrawal criteria, or for a maximum of 34 cycles (for cycles 19–34, only patients with partial response will receive BI 1387446), whichever occurs first. Primary endpoints are the MTD based on number of dose-limiting toxicities (DLTs) and number of patients with DLTs. Secondary endpoints are objective response rate (based on RECIST 1.1 criteria) and best change from baseline in size of target and injected (and uninjected) lesions. Plasma, blood, and tumor tissue will be collected at baseline and on-therapy for pharmacodynamic analyses. The trial is actively recruiting, and eight patients have been treated as of December 2020. Citation Format: Kevin Harrington, Eileen Parkes, Jared Weiss, Mathew Ingham, Andrés Cervantes, Emiliano Calvo, Ute Klinkhardt, Patricia Sikken, Michael Schmohl, Elena Garralda. Phase I, first-in-human trial evaluating BI 1387446 (STING agonist) alone and in combination with ezabenlimab (BI 754091; anti-PD-1) in solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT217.

Atypical Parathyroid Adenoma in a Young Man

Patient is a 38-year-old man who developed sudden onset of pain in the upper left arm while carrying a case of water. The pain recurred periodically over the next few months. He presented to the emergency department where imaging showed a pathologic fracture in the proximal left humerus through a lytic lesion. Laboratory testing showed: calcium 13.8 mg/dL (8.5–10.1 mg/dL), 25-OH vitamin D 8 ng/mL (31–100 ng/mL), parathyroid hormone 1583.1 pg/mL (18.5–88 pg/mL). Neck ultrasound showed a complex nodule in the left neck measuring 4.2 x 1.7 x 2.5 cm. Subsequent biopsy of the left arm lesion showed a Brown tumor. The patient was referred to endocrinology. There was concern for parathyroid carcinoma given the elevated parathyroid hormone and large neck lesion. Technetium-99m sestamibi scan showed a 4.1 x 2.6 x 2.5 cm mass posterior to the left thyroid lobe. He subsequently underwent left hemithyroidectomy and parathyroidectomy. Pathology revealed a 3.1 cm parathyroid mass with scattered fibrous bands, foci of prominent nucleoli and foci of sheet-like trabecular and spindled architecture. It was without necrosis, lymphovascular invasion, perineural invasion, increased mitotic activity, atypical mitoses or invasion into adjacent structures. Thus, it was classified as an atypical parathyroid adenoma.Primary hyperparathyroidism is the third most common endocrine disorder, but fewer than 2% occur as a result of an atypical parathyroid adenoma. Patients with an atypical parathyroid adenoma tend to have a more dramatic clinical presentation compared to those with classic adenoma. We see higher calcium and parathyroid hormone levels. Atypical parathyroid adenomas are classified as such due to other features which place the lesion at a higher risk for malignant behavior including higher mitotic activity, adherence to adjacent structures, banding fibrosis and a growth pattern that is either solid or trabecular. In contrast to parathyroid carcinoma, atypical parathyroid adenomas do not show invasion into the surrounding tissues or lymphatic/vascular vessels, and there should be no evidence of metastatic disease. The exact definition of an atypical parathyroid adenoma varies among institutions, and recognition of the defining features (or lack thereof) necessitates an experienced endocrine pathologist.Due to their uncertain malignant potential, patients with an atypical parathyroid adenoma should undergo routine surveillance for recurrence. Routine follow-up of calcium, parathyroid hormone and imaging is indicated to detect for recurrence. A CDC73 germline mutation is associated with recurrence compared to CDC73-negative patients. Parafibromin expression is also thought to play a role although studies so far have had discrepant results.

Ulcerated Arm Lesion in a 10-day-old Girl

1. Brittany Lehrer, MD* 2. Kyle Pronko, MD*,† 3. Alina G. Burek, MD*,† 1. *Medical College of Wisconsin, Milwaukee, WI 2. †Children’s Wisconsin, Milwaukee, WI 1. Address correspondence to Brittany Lehrer, MD, Children’s Corporate Center, Suite 730, 999 N 92nd St, Milwaukee, WI 53226. E-mail: blehrer{at}mcw.edu A 10-day-old girl presents with a progressive right upper extremity skin lesion. She was born large for gestational age at term via cesarean delivery for fetal distress. Pregnancy was complicated by diet-controlled gestational diabetes and a maternal history of genital herpes. The mother received prophylactic valacyclovir and no active herpes lesions developed during pregnancy. Immediately after birth, the infant was noted to have a 2-cm, tender, well-circumscribed area of erythema and induration over the right antecubital fossa. The extremity also had decreased movement, diminished radial pulse, and weak grasp reflex. Otherwise, she was well-appearing and her examination was normal. Radiographs of the forearm and clavicle were negative for fracture. She was diagnosed with hematoma and possible brachial plexus injury and discharged from the nursery on postnatal day 3 with the arm immobilized in a sling and acetaminophen as needed for pain. Since discharge from the nursery, the lesion has spread, ulcerated, and started draining malodorous white discharge, so the patient returns for evaluation on postnatal day 10. On physical examination, she has a poorly demarcated, erythematous, tender, indurated, circumferential plaque that extends from the mid-upper arm through the antecubital fossa to the mid-forearm. The center of the lesion is violaceous and ulcerated with white discharge (Fig 1). The affected extremity has decreased spontaneous movement, weak radial pulse, nearly absent grasp reflex, and she has pain with passive manipulation of the affected elbow. Her vital signs and the remainder of her physical examination are normal. Complete blood cell count with differential, procalcitonin, and c-reactive protein are within normal limits for age. Blood culture and herpes simplex virus polymerase chain reaction …

Familial aggregation of subcutaneous panniculitis-like T cell lymphoma

Rationale:Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare subtype of cutaneous lymphoma, which was first defined as a clinical entity in 1991 as a cytotoxic T-cell lymphoma preferentially infiltrating subcutaneous tissue. Herein, we report 2 patients of SPTCL who are a pair of twin brothers.Patient concerns:The disease afflicted the monozygotic twin brothers at different time with an interval period of 5 years. The older twin brother had disease onset at 27 years of age. In June 2012, he developed prolonged fever accompanied by subcutaneous nodules in the left upper arm and left chest due to unknown origin. The younger twin brother had disease onset at 32 years of age. In June 2017, the younger brother presented with repeated high fever for more than 10 days, accompanied by head distension.Diagnosis:On August 7, 2012, skin biopsy was performed on the lesion of left upper arm of the older twin brother, and then, a diagnosis of subcutaneous panniculitis-like T cell lymphoma (SPTCL) was made. On June 19, 2017, the younger twin brother underwent whole-body fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography for diagnosis. Soon afterwards, abdominal subcutaneous nodule resection and biopsy was performed on June 28, 2018, and the specimen was diagnosed as SPTCL.Interventions:For the older brother, a total of 14 systemic chemotherapy sessions were performed from August 16, 2012, to September 21, 2014. For the younger brother, a total of 9 systemic chemotherapy sessions were performed from July 14, 2017, to March 8, 2018, then he was switched to oral chemotherapy with chidamide twice a week for 6 months.Outcomes:The older twin brother died in March 2015, the younger brother has recovered well and is no longer receiving any treatmentLessons:To the best of our knowledge, twin brothers both having this disease has never been previously reported. Moreover, some of the involved areas are also extremely rare detected by fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography at initial stage. It is beneficial to people to gain some new understanding for SPTCL by this special case and some extremely unusual involved sites in the younger twin brother.

Underwater versus conventional endoscopic resection of nondiminutive nonpedunculated colorectal lesions: a prospective randomized controlled trial (with video)

Incomplete resection of colorectal neoplasia decreases the efficacy of colonoscopy. Conventional resection (CR) of polyps, performed in a gas-distended colon, is the current standard, but incomplete resection rates of approximately 2% to 30% for nondiminutive (>5mm), nonpedunculated lesions are reported. Underwater resection (UR) is a novel technique. The aim of this study was to determine the incomplete resection rates of colorectal lesions removed by UR versus CR. In a randomized controlled trial, patients with small (6-9mm) and large (≥10mm) nonpedunculated lesions were assigned to CR (gas-distended lumen) or UR (water-filled, gas-excluded lumen). Small lesions in both arms were removed with a dedicated cold snare. For CR, large lesions were removed with a hot snare after submucosal injection. For UR, large lesions were removed with a hot snare without submucosal injection. Four-quadrant biopsy samples around the resection sites were used to evaluate for incomplete resection. Four hundred sixty-two eligible polyps (248 UR vs 214 CR) from 255 patients were removed. Incomplete resection rates for UR and CR were low and did not differ (2% vs 1.9%, P= .91). UR was performed significantly faster for lesions≥10mm in size (10-19mm, 2.9 minutes vs 5.6 minutes, P< .0001); ≥20 mm, 7.3 minutes vs 9.5 minutes, P = .015). Low incomplete resection rates are achievable with UR and CR. UR is effective and safe with the advantage of faster resection and potential cost savings for removal of larger (≥10mm) lesions by avoiding submucosal injection. As an added approach, UR has potential to improve the cost-effectiveness of colonoscopy by increasing efficiency and reducing cost while maintaining quality. (Clinical trial registration number: NCT02889679.).

Sporotrichosis in the Highlands of Madagascar, 2013-20171.

Sporotrichosis is a saprozoonotic fungal infection found mostly in tropical and subtropical areas. Few case reports in Madagascar have been published. To document sporotrichosis epidemiology in Madagascar, we conducted a cross-sectional study. During March 2013–June 2017, we recruited from select hospitals in Madagascar patients with chronic cutaneous lesions suggestive of dermatomycosis. Sporotrichosis was diagnosed for 63 (42.5%) of 148 patients. All but 1 patient came from the central highlands, where the prevalence was 0.21 cases/100,000 inhabitants. Frequency was high (64.7%) among patients <18 years of age. Sporotrichosis was diagnosed for 73.8% of patients with arm lesions, 32.3% with leg lesions, and 15.4% with lesions at other sites. Molecular identification identified 53 Sporothrix schenckii isolates. Among the 32 patients who were followed up, response to itraconazole was complete or major for 15 and minor for 17. Overall, endemicity of sporotrichosis in Madagascar was high, concentrated in the highlands.

1154FFR guided acute complete revascularization versus culprit lesion only treatment in patients presenting with STEMI and multi vessel disease; final 3-year outcome data from Compare-Acute trial

Abstract Background Compare-Acute trial showed a 1-year superior outcome of FFR-guided acute complete revascularization (FFR-CR) compared to culprit-lesion-only revascularization (CLO) in patients presenting with ST-segment elevation myocardial infarction (STEMI) and multi-vessel disease (MVD). Long-term outcome results are unknown. Purpose To evaluate if FFR-CR strategy is superior to CLO strategy in terms of outcome at 3 year follow-up. Methods Compare-Acute is a multicenter, investigator-initiated prospective randomized controlled trial that involved 24 sites. Patients with STEMI and MVD were randomized, after successful primary PCI towards FFR-CR or CLO treatment strategies with a 1:2 ratio (295 pts vs 590 pts). All stenosis ≥50% in the non-infarct artery were investigated by FFR in both arms. In the FFR-CR arm, all non-culprit (NC) lesions with a FFR ≤0.80 were treated by PCI. In the CLO arm pts underwent blinded FFR procedure of the NC lesions. Further treatment of these lesions was based on symptoms and/or ischemia testing during follow-up with an allowed treatment window of 45 days. The primary endpoint was defined as a composite of all-cause mortality, non-fatal myocardial infarction, any revascularization and cerebrovascular events (MACCE) at 12 months. The major secondary endpoint is MACCE from both strategies up to 3-year follow-up. Results 1-year clinical outcomes have already been presented and published. At 36 months the composite end-point of MACCE occurred in 46 patients in the FFR-CR group vs 178 patients in the CLO group (15.6% vs 30.2%; HR 0.46, 95% CI 0.29–0.59; p&lt;0.01), as shown in Fig. 1. The incidence of death (4 pts vs 10 pts; 1.4% vs 1.7%; HR 0.86, 95% CI 0.39–1.8; p=0.71), MI (20 pts vs 53 pts; 7.1% vs 9.3%; HR 0.74, 95% CI 0.44–1.24; p=0.25) and stroke (1 pt vs 7 pts; 0.3% vs 1.2%; HR 0.29, 95% CI 0.03–2.3; p=0.24) was not significantly different in the two groups, but revascularizations were significantly higher in the CLO group: 37 patients in the FFR-CR group vs 149 patients in the CLO group (13.0% vs 26.0%; HR 0.45; 95% CI 0.31–0.64; p&lt;0.01). Furthermore, in a subgroup analysis, when we considered only patients with FFR positive non-culprit lesions in both arms, we found a higher incidence of MI at follow-up in the CLO arm compared to the FFR-CR arm: 30/224 vs 13/194 (13.4% vs 6.7%; p 0.03). MACCE-free survival at 3 years Conclusion With this analysis of the Compare-Acute trial we confirm that the benefit of a FFR-guided complete revascularization strategy in patients with STEMI and MVD is maintained at 3 years of follow-up. This difference is mainly driven by increased revascularizations in the CLO arm, but also by increased incidence of MI in the CLO subgroup with FFR+ lesions that were left untreated.

Phonotherapeutic Intervention in Patients With Mucosal Leishmaniasis Sequelae

To characterize the voice before and after speech-language intervention, with Humming nasal sound in patients with sequelae Mucosal Leishmaniasis (ML) and Cutaneous Leishmaniasis (CL). Collection of phonation /a:/ from 44 patients with ML and CL for perceptual voice analysis and computed acoustic. The Wilcoxon nonparametric test and Fisher's exact test were used, with significance level of 5%. It was observed, prespeech therapy, that 27.7% of participants with ML presented asthenic vocal quality, and for the acoustics characteristics there was a statistically significant result for measures of frequency, frequency disturbance, noise, and subharmonic measurements, indicating phonatory instability, weakness, and noise emission giving the emission a feeling of vocal weakness. After therapy, the subharmonic segment measurements for the group with ML, showing reduction noise emission. Patients with CL had more grade 1 instability (36.4%), indicating tremor in vocal tract structures. After speech therapy, this group presented a reduction in the degree of roughness and reduction of the frequency disturbance measures, indicating a decrease in tension in the larynx and pharynx. Even after completing treatment for LM, patients may experience vocal changes due to the sequelae of the disease, like vocal alterations due to nasal lesions or in other locations that interfere in the correct vocal emission. As for participants with CL, no vocal changes would be expected, since these patients present thorax, leg and arm lesions that would not cause problems for the voice. Nevertheless, the two groups of participants presented vocal changes to different degrees before vocal therapy. However, it was observed that patients with ML present vocal alterations with more severe degrees. After the speech-language intervention, the participants of both groups showed vocal improvement, but the group with CL presented more vocal benefits, possibly due to the previous vocal alterations not being so severe.