Brentuximab vedotin demonstrates an objective response in a patient with refractory CD30+ primary mediastinal B-cell lymphoma.

Diffuse large B-cell lymphomas (DLBCL) with MYC translocations combined with translocations involving BCL-2 or BCL-6 are referred to as double-hit lymphomas. These lymphomas are generally refractory to currently available therapies and have a poor prognosis. Primary mediastinal B-cell lymphoma (PMBL) is a rare subtype of DLBCL, which shares clinical, pathologic, and genetic similarities with classical Hodgkin's lymphoma. Unlike DLBCL, rearrangements involving MYC, BCL-2, and BCL-6 are typically absent in PMBL. We present a patient with PMBL who had increased gene copy numbers of MYC and BCL-2 along with increased protein expression of BCL-2 (c-Myc expression was about 15%-20% by immunostain). The disease was refractory to standard and salvage chemotherapies. The lymphoma, however, responded to brentuximab vedotin, a CD30-directed chemoimmunoconjugate.

The beta adrenergic receptor antagonist propranolol alters mitogenic and apoptotic signaling in late stage breast cancer.

BACKGROUND: Substantial evidence supports the use of inexpensive ß-AR antagonists (beta blockers) against a variety of cancers, and the ß-AR antagonist propranolol was recently approved by the European Medicines Agency for the treatment of soft tissue sarcomas. Prospective and retrospective data published by our group and others suggest that non-selective ß-AR antagonists are effective at reducing proliferative rates in breast cancers, however the mechanism by which this occurs is largely unknown. METHODS: In this study, we measured changes in tumor proliferation and apoptosis in a late stage breast cancer patient treated with neoadjuvant propranolol. We expounded upon these clinical findings by employing an in vitro breast cancer model, where we used cell-based assays to evaluate propranolol-mediated molecular alterations related to cell proliferation and apoptosis. RESULTS: Neoadjuvant propranolol decreased expression of the pro-proliferative Ki-67 and pro-survival Bcl-2 markers, and increased pro-apoptotic p53 expression in a patient with stage III breast cancer. Molecular analysis revealed that ß-AR antagonism disrupted cell cycle progression and steady state levels of cyclins. Furthermore, propranolol treatment of breast cancer cells increased p53 levels, enhanced caspase cleavage, and induced apoptosis. CONCLUSION: Collectively, these data provide support for the incorporation of ß-AR antagonists into the clinical management of breast cancer, and elucidate a partial molecular mechanism explaining the efficacy of ß-AR antagonists against this disease.

Thoracic Paraspinal Castleman Disease in a Young Mexican-American Man with Postcoital Hematuria.

BACKGROUND: Castleman disease (CD) is an uncommon disorder of deregulated lymphoproliferation with unicentric (UCD) and multicentric forms based on extent of nodal involvement. Gross resection with histopathologic analysis remains the gold standard for diagnosis of UCD and is curative in most cases. Symptomatic paraspinal UCD is a rare presentation with potentially dangerous complications, and its tendency to mimic more common spinal tumors presents a significant diagnostic challenge. CASE PRESENTATION: A 25-year-old Hispanic man with no past medical history was evaluated for a known left-sided paraspinal mass that was incidentally discovered during an emergency department work-up for hematuria. Computed tomography on initial presentation revealed a 5.3 cm × 3.3 cm × 4.8 cm heterogeneously enhancing left paraspinal mass adjacent to the T11 vertebral body with tonguelike extension into the T11-T12 neural foramen. Although he remained neurologically intact throughout most of the diagnostic work-up, an inconclusive biopsy, worsening hematuria, and late-onset radiculopathy with severe back pain prompted surgical intervention. Microscopic histomorphology was consistent with CD. He continued to have intermittent hematuria and dysuria postoperatively, but repeat computed tomography at 7 months confirmed no recurrence of the mass. CONCLUSIONS: Compared with previous reports, our case of postcoital hematuria and radiculopathy accompanying a paraspinal thoracic mass in a young Mexican-American man is a unique presentation. Awareness and early consideration of UCD in the work-up of a paraspinal mass may spare affected patients adverse and dangerous sequelae, such as spinal cord compression and excessive intraoperative hemorrhage.

Lip Repositioning with Vestibular Shallowing Technique for Treatment of Excessive Gingival Display with Various Etiologies.

Improvement of smile esthetics is a major goal of modern dentistry. Various treatment modalities have been proposed to correct excessive gingival display (EGD), depending on the identified etiologies. This study reports on the clinical and patient-centered outcomes of a novel lip repositioning technique with vestibular shallowing approach in the treatment of three types of EGD with varying etiologies. Periosteal fenestration with cicatrization (scarification) was performed at the mucogingival junction to ensure the stability of esthetic outcomes. Suspensory triangular sutures and extraoral tissue stabilization tapes were used to facilitate the cicatrization process during the healing phase of this novel technique. Postoperative clinical examination revealed 84% reduction in gingival display that remained stable for 13 to 16 months with a high level of patient satisfaction.

Periodontal Regenerative Treatment of Intrabony Defects in the Esthetic Zone Using Modified Vestibular Incision Subperiosteal Tunnel Access (M-VISTA).

Periodontal regenerative treatment of intrabony defects in the esthetic zone often poses a significant challenge to clinicians. Various materials and techniques have been proposed to achieve periodontal regeneration. This article presents modified vestibular incision subperiosteal tunnel access (M-VISTA) for treatment of intrabony defects in the esthetic zone. Two cases were treated using the proposed approach with enamel matrix derivatives and demineralized freeze-dried bone allograft to optimize the regenerative outcomes without affecting the soft tissue profile in the esthetic zone. Two different indications were described with addition of acellular dermal matrix and specific suturing techniques based on each particular clinical scenario. Clinical and radiographic follow-up of 18 months revealed successful outcomes of the proposed minimally invasive approach with no postoperative gingival recession. Patient-centered outcomes were highlighted as another major consideration in periodontal regeneration.

Acute myeloid leukemia with KMT2A-SEPT5 translocation: A case report and review of the literature.

Chromosomal rearrangement involving the KMT2A gene is one of the most common genetic alteration in acute myeloid leukemia. A total of 135 different KMT2A rearrangements have been identified, where 94 translocation partner genes are now characterized at the molecular level. Of these 94 translocation partner genes, 35 translocation partner genes occur recurrently, but only 9 specific gene fusions account for more than 90% of cases. Translocation of KMT2A with SEPT5 gene at 22q11.2 is rare, with few reported cases in the literature. In this report, we are presenting a case of KMT2A-SEPT5 fusion in de novo acute myeloid leukemia with t(11;22)(q23;q11.2) with a review of the literature.

A New Prognostication System for Dental Implants.

Given the popularity of dental implants, determining their prognosis is an integral component of dental practice. An accurate prognosis is crucial to development of an appropriate treatment plan and may require alterations as overall status or the status of implants or natural teeth change. The importance of an established set of factors for determining implant prognosis would be highlighted in dentist-patient communication and in interdisciplinary collaboration. The main objective of the proposed prognostication system is short- and long-term success of dental implants. The aim of this study was to review evidence-based prognostic factors including surgical, peri-implant, prosthetic, and overall considerations in implant dentistry and to propose a new prognostication system. A blind survey was taken by 67 prosthodontists, periodontists, and oral surgeons at three dental schools to assess the importance of each consideration based on clinical experience and available evidence. The results supported incorporation of the comprehensive review of evidence-based prognostic factors into the proposed dynamic system for dental implant prognostication.

Dermatopathic Lymphadenitis Mimicking Breast Cancer with Lymphatic Metastasis: A Case Report and Discussion.

BACKGROUND Dermatopathic lymphadenitis is a rare benign lymphatic hyperplasia commonly associated with exfoliative or eczematoid dermatitis. Of interest, this condition can be confused with lymphatic metastasis in adults. CASE REPORT In this report, we describe the case of a 56-year-old woman diagnosed with left breast invasive ductal carcinoma in remission, who presented with dermatopathic lymphadenitis mimicking breast cancer recurrence. CONCLUSIONS Dermatopathic lymphadenitis is a benign entity that needs to be considered in the differential diagnosis of lymphadenopathy. Pursuing extensive workup in asymptomatic patients with a similar presentation and initial negative tests for malignancy recurrence is not recommended.

The Prevalence of Biopsy-Proven Eosinophilic Esophagitis in Hispanics Undergoing Endoscopy Is Infrequent Compared to Caucasians: A Cross-Sectional Study.

INTRODUCTION: The prevalence of eosinophilic esophagitis (EoE), a chronic, immune-mediated, clinicopathologic, inflammatory disorder, has been well described in the pediatric and adult Caucasian population but not as well studied in the Hispanic population. The major aims of this study are to determine the prevalence and gene expression profile of EoE in these populations. METHODS: This is a retrospective cohort study of patients from two institutions predominantly serving a Hispanic population. Patients included at Los Angeles County Hospital (LACH) had an esophagogastroduodenoscopy (EGD) and esophageal biopsies performed for evaluation of dysphagia and/or food impaction, while patients included from the University Hospital Medical Center of El Paso (UHMCEP) had an EGD and esophageal biopsies performed for any appropriate clinical indication. Gene expression analysis which has been shown to accurately diagnose EOE in Caucasians was performed for 9 patients at UHMCEP to determine its accuracy in Hispanics. RESULTS: At LACH, 234 patients were included in the study of whom 155 (66.3%) were Hispanic and 22 (9.4%) were Caucasian. 3.2% of the Hispanic patients and 9.1% of the Caucasian patients were diagnosed with EOE with threefold difference. At UHMCEP 1700 patients were included of whom 1350 (79.4%) were Hispanic and 179 (10.5%) were Caucasian. 0.96% of the Hispanic patients and 7.26% of the Caucasian patients were diagnosed with EOE with a sevenfold difference. Gene expression accurately diagnosed EOE in a small number of both Hispanics and Caucasians who underwent analysis. CONCLUSIONS: Hispanic patients at LAC and UMHCEP had a significantly lower prevalence of EOE as compared to Caucasians at these two institutions and a lower prevalence as compared to Caucasians with EOE previously reported in the literature. Gene expression analysis, which has previously been shown to accurately diagnose EOE in Caucasian patients, accurately diagnosed EOE in a small sample of this Hispanic population. Based on this similar gene expression, other factors such as environmental, ethnic, and cultural causes should be investigated to explain the markedly lower prevalence of EOE in Hispanics.

PD-1 and PD-L1 expression in bone and soft tissue sarcomas.

PD-1 and its ligands have been shown to play a significant role in evasion of malignant tumour cells from the immune system. Last year, the Unites States Food and Drug Administration (FDA) approved anti-PD-1 inhibitors for treatment of non-small cell lung carcinoma and recently expanded the use of immunotherapy for metastatic urothelial cell carcinoma and Hodgkin lymphoma. However, studies on expression of PD-1 and its ligand in malignant bone and soft tissue sarcoma are sparse. In this study, we evaluated PD-1 and PD-L1 expression on variants of liposarcomas and rhabdomyosarcomas, osteosarcomas and chondrosarcomas. Tissue microarrays (TMAs) for liposarcomas (well differentiated, myxoid/round cell, and pleomorphic), rhabdomyosarcomas (alveolar, embryonal, pleomorphic, and spindle cell), conventional osteosarcomas and chondrosarcomas were stained for PD-1 and PD-L1 antibodies. Adipose tissue, skeletal muscle, bone, osteochondroma and lipoma were used as control and benign counterparts. Western blot was performed to evaluate expression of PD-1 and PD-L1 in four sarcoma cell lines. Osteosarcomas, chondrosarcomas, and all variants of liposarcomas and rhabdomyosarcomas over-expressed PD-1 relative to normal tissue. Expression of PD-1 in rhabdomyosarcomas was associated with higher tumour stage. Only one case of pleomorphic liposarcoma, one case of pleomorphic rhabdomyosarcoma and two cases of alveolar rhabdomyosarcomas were positive for PD-L1. Normal adipose tissue, skeletal muscle, and bone were negative for both PD-1 and PD-L1 and lipomas and osteochondroma weakly expressed PD-1 but not PD-L1. Western blot confirmed the presence of PD-1 protein in all four sarcoma cell lines. Overall, our results showed cytoplasmic expression of PD-1 in the bone and soft tissue sarcomas, while PD-L1 was negative. Whether these data are an indication for effectiveness of immunotherapy in the management of malignant bone and soft tissue sarcomas remains to be elucidated.

Spontaneous Rupture of the Uterine Artery in an Otherwise Normal Pregnancy.

Spontaneous rupture of a uterine artery in pregnancy is associated with a high rate of mortality. Although uterine artery rupture has been associated with postpartum hemorrhage, it is rarely found during pregnancy. Unfortunately, clinical signs and symptoms are usually vague and nonspecific. We report a case of a 36-year-old woman at 20 weeks gestation presenting with abdominal pain who was found to have a spontaneous uterine artery rupture. To our knowledge, this is the first case report demonstrating imaging findings in a patient with this condition. Our patient underwent successful ligation of the uterine vessel with preservation of both mother and fetus. We will discuss possible etiologies of uterine artery rupture during pregnancy, associated imaging findings, and management options.

Pathological Findings of the Antral and Pyloric Smooth Muscle in Patients with Gastroparesis-Like Syndrome Compared to Gastroparesis: Similarities and Differences.

BACKGROUND: Gastroparesis (GP)-like syndrome presents with the symptoms of GP but without delayed gastric emptying (GE). Whether GP-like syndrome is part of a spectrum of GP is not clear. This study aimed to compare the histopathological features of antral and pyloric smooth muscle tissue in GP and GP-like syndrome. METHODS: Full-thickness antral and/or pyloric biopsies were obtained from 37 GP and 18 GP-like syndrome patients who underwent abdominal surgery to place a gastric electrical stimulator or jejunal feeding tube and/or pyloroplasty. The tissues were stained with H&E, C-Kit, and trichrome. Based on previous control data, an interstitial cells of Cajal (ICC) count of <10 per high power field in the antrum and/or pylorus was considered depletion. Baseline total symptom score (TSS) was recorded. RESULTS: Twenty-four GP and 7 GP-like patients had pyloric biopsies. Pyloric ICC loss was observed in 20/24 (83.3%) GP and 2/7 (28.6%) GP-like patients (p < 0.01). Fibrosis was detected in the pyloric tissue of 20/24 (83.3%) GP and 2/7 (28.6%) GP-like patients who had pyloric trichrome staining (p < 0.01). Seventeen out of 24 (70.8%) GP patients with pyloric biopsies had concomitant pyloric ICC loss and fibrosis, while only one GP-like patient had ICC loss and simultaneous pyloric fibrosis. GP patients had a greater TSS compared to GP-like patients. In GP patients, those with pyloric ICC loss had a greater TSS compared to those with normal ICC. GP patients with pyloric fibrosis had a higher TSS compared to those without pyloric fibrosis. CONCLUSIONS: Compared to GP-like patients, the pyloric histopathological findings of ICC loss and fibrosis are common in GP and predict a greater symptom score. These pathological findings might be considered as markers of "pyloric dysfunction" and explain delayed GE in GP.

The cellularity yield of three different 22-gauge endoscopic ultrasound fine needle aspiration needles.

BACKGROUND: Endoscopic ultrasound (EUS) fine needle aspiration (FNA) is an integral part in the diagnosis of pancreatic, intestinal and extra-intestinal masses or lesions. There is no clear data on the superiority of the core biopsy needle over standard 22-gauge needles. The aim of this study is to prospectively compare the cellularity yield of three commonly used 22-gauge FNA needles available in the US market. METHODS: This is a prospective, randomized study comparing the cellularity yield of three commercially available EUS needles (two standard FNA needles and core biopsy needle). Two blinded pathologists evaluated the cytology specimens based on an already agreed upon cytology score. We included adult patients (18-80 years old) who presented to our endoscopy unit for FNA of pancreatic or extrapancreatic masses. RESULTS: 109 patients (57 F, 52 M) were recruited to the study, 88 lesions were pancreatic lesions. 39 patients were recruited in the EZ Shot 2™ group, 36 in the Procore® group and 34 in the Expect™ group. The average cellularity score and the mean number of passes (SD) were not different between the three needles; P = 0.91 and P = 0.16, respectively. There was no difference between the three needles in obtaining an onsite diagnosis (P = 0.627) and no difference in reported adverse events between the three groups. CONCLUSION: The cellularity yields, the mean number of passes and reported adverse events were similar in the three compared 22-gauge needles. Diagn. Cytopathol. 2017;45:426-432. © 2017 Wiley Periodicals, Inc.

Enhanced expression of Programmed cell death 1 (PD-1) protein in benign vascular anomalies.

Programmed cell death 1 (PD-1) and its ligands have been shown to play a significant role in evasion of malignant tumour cells from the immune system. Last year, the United States Food and Drug Administration (FDA) approved anti-PD-1 inhibitors for treatment of non-small cell lung carcinoma and recently has approved anti-PD-L1 blocker for treatment of metastatic urothelial cell carcinoma. However, the role that the immune system might have on benign tumours including vascular anomalies has received less attention. In this study, we evaluated PD-1 and PD-L1 expression on two benign vascular anomalies: infantile haemangiomas and venous malformations. Tissue microarrays (TMAs) from these two entities were stained for PD-1 and PD-L1 antibodies. Blood vessels from normal tissue were used as control. The endothelial cells in both infantile haemangioma and venous malformation showed high expression of PD-1 but were negative for PD-L1. Endothelial cells within the blood vessels in normal tissues were negative for both PD-1 and PD-L1. Our results showed over-expression of PD-1 in subsets of vascular anomalies, while PD-L1 was negative. This would raise the possibility of immunotherapy in benign vascular tumour when other options are exhausted.

Use of non-selective ß-blockers is associated with decreased tumor proliferative indices in early stage breast cancer.

Previous studies suggest beta-adrenergic receptor (ß-AR) antagonists (ß-blockers) decrease breast cancer progression, tumor metastasis, and patient mortality; however the mechanism for this is unknown. Immunohistochemical analysis of normal and malignant breast tissue revealed overexpression of ß1-AR and ß3-AR in breast cancer. A retrospective cross-sectional study of 404 breast cancer patients was performed to determine the effect of ß-blocker usage on tumor proliferation. Our analysis revealed that non-selective ß-blockers, but not selective ß-blockers, reduced tumor proliferation by 66% (p < 0.0001) in early stage breast cancer compared to non-users. We tested the efficacy of propranolol on an early stage breast cancer patient, and quantified the tumor proliferative index before and after treatment, revealing a propranolol-mediated 23% reduction (p = 0.02) in Ki67 positive tumor cells over a three-week period. The anti-proliferative effects of ß-blockers were measured in a panel of breast cancer lines, demonstrating that mammary epithelial cells were resistant to propranolol, and that most breast cancer cell lines displayed dose dependent viability decreases following treatment. Selective ß-blockers alone or in combination were not as effective as propranolol at reducing breast cancer cell proliferation. Molecular analysis revealed that propranolol treatment of the SK-BR-3 breast cancer line, which showed high sensitivity to beta blockade, led to a reduction in Ki67 protein expression, decreased phosphorylation of the mitogenic signaling regulators p44/42 MAPK, p38 MAPK, JNK, and CREB, increased phosphorylation of the cell survival/apoptosis regulators AKT, p53, and GSK3ß. In conclusion, use of non-selective ß-blockers in patients with early stage breast cancer may lead to decreased tumor proliferation.

Calcitonin-Negative Neuroendocrine Tumor of the Thyroid.

Neuroendocrine tumors (NETs) of the thyroid are rare; the most common type is medullary thyroid carcinoma (MTC). They are derived from parafollicular cells (C-cells) that usually express calcitonin, chromogranin, and carcinoembryonic antigen. Calcitonin-negative NETs of the thyroid are extremely rare, and the origin of these tumors is unclear. Whereas some believe that these tumors are from follicular cells, recent reports have shown expression of calcitonin gene-related peptide in these tumors, indicating parafollicular C-cell origin. Here, we report a case of calcitonin-negative NET of the thyroid in a 74-year-old woman, with review of the literature.