Bone Surface Tumours and Tumour-Like Conditions
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Infiltrating Myeloid Cells Drive Osteosarcoma Progression Via GRM4 Regulation of IL23
Published OnlineFirst September 16, 2019; DOI: 10.1158/2159-8290.CD-19-0154 RESEARCH BRIEF Infi ltrating Myeloid Cells Drive Osteosarcoma Progression via GRM4 Regulation of IL23 Maya Kansara 1 , 2 , Kristian Thomson 1 , Puiyi Pang 1 , Aurelie Dutour 3 , Lisa Mirabello 4 , Francine Acher5 , Jean-Philippe Pin 6 , Elizabeth G. Demicco 7 , Juming Yan 8 , Michele W.L. Teng 8 , Mark J. Smyth 9 , and David M. Thomas 1 , 2 ABSTRACT The glutamate metabotropic receptor 4 (GRM4 ) locus is linked to susceptibility to human osteosarcoma, through unknown mechanisms. We show that Grm4 − / − gene– targeted mice demonstrate accelerated radiation-induced tumor development to an extent comparable with Rb1 +/ − mice. GRM4 is expressed in myeloid cells, selectively regulating expression of IL23 and the related cytokine IL12. Osteosarcoma-conditioned media induce myeloid cell Il23 expression in a GRM4-dependent fashion, while suppressing the related cytokine Il12 . Both human and mouse osteosarcomas express an increased IL23:IL12 ratio, whereas higher IL23 expression is associated with worse survival in humans. Con- sistent with an oncogenic role, Il23−/− mice are strikingly resistant to osteosarcoma development. Agonists of GRM4 or a neutralizing antibody to IL23 suppressed osteosarcoma growth in mice. These fi ndings identify a novel, druggable myeloid suppressor pathway linking GRM4 to the proinfl ammatory IL23/IL12 axis. SIGNIFICANCE: Few novel systemic therapies targeting osteosarcoma have emerged in the last four decades. Using insights gained from a genome-wide association study and mouse modeling, we show that GRM4 plays a role in driving osteosarcoma via a non–cell-autonomous mechanism regulating IL23, opening new avenues for therapeutic intervention. -
Clinical Features of Benign Tumors of the External Auditory Canal According to Pathology
Central Annals of Otolaryngology and Rhinology Research Article *Corresponding author Jae-Jun Song, Department of Otorhinolaryngology – Head and Neck Surgery, Korea University College of Clinical Features of Benign Medicine, 148 Gurodong-ro, Guro-gu, Seoul, 152-703, South Korea, Tel: 82-2-2626-3191; Fax: 82-2-868-0475; Tumors of the External Auditory Email: Submitted: 31 March 2017 Accepted: 20 April 2017 Canal According to Pathology Published: 21 April 2017 ISSN: 2379-948X Jeong-Rok Kim, HwibinIm, Sung Won Chae, and Jae-Jun Song* Copyright Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College © 2017 Song et al. of Medicine, South Korea OPEN ACCESS Abstract Keywords Background and Objectives: Benign tumors of the external auditory canal (EAC) • External auditory canal are rare among head and neck tumors. The aim of this study was to analyze the clinical • Benign tumor features of patients who underwent surgery for an EAC mass confirmed as a benign • Surgical excision lesion. • Recurrence • Infection Methods: This retrospective study involved 53 patients with external auditory tumors who received surgical treatment at Korea University, Guro Hospital. Medical records and evaluations over a 10-year period were examined for clinical characteristics and pathologic diagnoses. Results: The most common pathologic diagnoses were nevus (40%), osteoma (13%), and cholesteatoma (13%). Among the five pathologic subgroups based on the origin organ of the tumor, the most prevalent pathologic subgroup was the skin lesion (47%), followed by the epithelial lesion (26%), and the bony lesion (13%). No significant differences were found in recurrence rate, recurrence duration, sex, or affected side between pathologic diagnoses. -
Bone and Soft Tissue Tumors Have Been Treated Separately
EPIDEMIOLOGY z Sarcomas are rare tumors compared to other BONE AND SOFT malignancies: 8,700 new sarcomas in 2001, with TISSUE TUMORS 4,400 deaths. z The incidence of sarcomas is around 3-4/100,000. z Slight male predominance (with some subtypes more common in women). z Majority of soft tissue tumors affect older adults, but important sub-groups occur predominantly or exclusively in children. z Incidence of benign soft tissue tumors not known, but Fabrizio Remotti MD probably outnumber malignant tumors 100:1. BONE AND SOFT TISSUE SOFT TISSUE TUMORS TUMORS z Traditionally bone and soft tissue tumors have been treated separately. z This separation will be maintained in the following presentation. z Soft tissue sarcomas will be treated first and the sarcomas of bone will follow. Nowhere in the picture….. DEFINITION Histological z Soft tissue pathology deals with tumors of the classification connective tissues. of soft tissue z The concept of soft tissue is understood broadly to tumors include non-osseous tumors of extremities, trunk wall, retroperitoneum and mediastinum, and head & neck. z Excluded (with a few exceptions) are organ specific tumors. 1 Histological ETIOLOGY classification of soft tissue tumors tumors z Oncogenic viruses introduce new genomic material in the cell, which encode for oncogenic proteins that disrupt the regulation of cellular proliferation. z Two DNA viruses have been linked to soft tissue sarcomas: – Human herpes virus 8 (HHV8) linked to Kaposi’s sarcoma – Epstein-Barr virus (EBV) linked to subtypes of leiomyosarcoma z In both instances the connection between viral infection and sarcoma is more common in immunosuppressed hosts. -
CASE REPORT Intradermal Nevus of the External Auditory Canal
Int. Adv. Otol. 2009; 5:(3) 401-403 CASE REPORT Intradermal Nevus of the External Auditory Canal: A Case Report Sedat Ozturkcan, Ali Ekber, Riza Dundar, Filiz Gulustan, Demet Etit, Huseyin Katilmis Department of Otorhinolaryngology and Head and Neck Surgery ‹zmir Atatürk Research and Training Hospital, Ministry of Health, ‹ZM‹R-TURKEY (SO, AE, FG, DE, HK) Department of Otorhinolaryngology and Head and Neck Surgery Etimesgut Military Hospital , ANKARA-TURKEY (RD) Intradermal nevus is the most common skin tumor in humans; however, its occurrence in the external auditory canal (EAC) is uncommon. The clinical manifestations of pigmented nevus of the EAC have been reported to include ear fullness, foreign body sensation, hearing impairment, and otalgia, but some cases were asymptomatic and were found incidentally. The treatment of choice for a symptomatic intradermal nevus in the EAC is complete excision. There has been no recurrence reported in the literature . A pedunculated, papillomatous hair-bearing lesion was detected in the external auditory canal of the patient who was on follow-up for pruritus. Clinical and pathologic features of an intradermal nevus of the external auditory canal are presented, and the literature reviewed. Submitted : 14 October 2008 Revised : 01 July 2009 Accepted : 09 July 2009 Intradermal nevus is the most common skin tumor in left external auditory canal. Otomicroscopic humans; however, its occurrence in the external examination revealed a pedunculated, papillomatous auditory canal (EAC) is uncommon [1-4]. Intradermal hair-bearing lesion in the postero-inferior cartilaginous nevus is considered to be a form of benign cutaneous portion of the external auditory canal (Figure 1). -
Primary Ewing Sarcoma/Primitive Neuroectodermal Tumor of the Kidney: the MD Anderson Cancer Center Experience
cancers Article Primary Ewing Sarcoma/Primitive Neuroectodermal Tumor of the Kidney: The MD Anderson Cancer Center Experience Nidale Tarek 1,2,*, Rabih Said 3, Clark R. Andersen 4, Tina S. Suki 1, Jessica Foglesong 1,5 , Cynthia E. Herzog 1, Nizar M. Tannir 6, Shreyaskumar Patel 7, Ravin Ratan 7, Joseph A. Ludwig 7 and Najat C. Daw 1,* 1 Department of Pediatrics, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; [email protected] (T.S.S.); [email protected] (J.F.); [email protected] (C.E.H.) 2 Department of Pediatrics and Adolescent Medicine, American University of Beirut Medical Center, Beirut 1107, Lebanon 3 Department of Investigational Cancer Therapeutics, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; [email protected] 4 Department of Biostatistics, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; [email protected] 5 Division of Hematology, Oncology, Neuro-Oncology & Stem Cell Transplant, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL 60611, USA 6 Department of Genitourinary Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; [email protected] 7 Department of Sarcoma Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; [email protected] (S.P.); [email protected] (R.R.); [email protected] (J.A.L.) * Correspondence: [email protected] (N.T.); [email protected] (N.C.D.); Tel.: +1-713-792-6620 (N.C.D.) Received: 27 August 2020; Accepted: 5 October 2020; Published: 11 October 2020 Simple Summary: The Ewing sarcoma family of tumors (ESFT)s rarely originate in the kidneys and their treatment is significantly different from the other common kidney tumors. -
A Case of Intradermal Melanocytic Nevus with Ossification (Nevus of Nanta)
197 A Case of Intradermal Melanocytic Nevus with Ossification (Nevus of Nanta) Young Bok Lee, M.D., Kyung Ho Lee, M.D., Chul Jong Park, M.D. Department of Dermatology, College of Medicine, The Catholic University of Korea, Seoul, Korea A 49-year-old woman presented with a 30-year history of asymptomatic plaque on her right temple. The histological examination revealed nests of nevus cells throughout the entire dermis. Bony spicules were seen just beneath the nevus cell nests in the lower dermis. Cutaneous ossification is an unusual event. Herein, we present a case of intradermal melanocytic nevus with unusual ossification (nevus of Nanta). To the best of our knowledge, this is the first such case report in the Korean literature. (Ann Dermatol (Seoul) 20(4) 197∼199, 2008) Key Words: Melanocytic nevus, Ossification INTRODUCTION drug intake or medical illness. The histological examination showed a dense proliferation of benign Ossification within the skin may occur in a nevus cells in the upper dermis. They were arranged variety of conditions, including pilomatricoma, basal in nests surrounding the hair follicles (Fig. 2). Bony cell carcinoma, appendageal and fibrous prolifera- spicules were seen in the lower dermis, underneath 1,2 tion, inflammation and trauma . The occurrence of the nevus cell nests. Some of them were compact ossification within a melanocytic nevus is an un- while others were surrounded by mature fatty tissue 3-5 usual event . (Fig. 3). Herein, we present a case of intradermal melano- cytic nevus with unusual ossification (nevus of Nanta). To the best our knowledge, this is the first such case report in the Korean literature. -
Pathogenesis and Current Treatment of Osteosarcoma: Perspectives for Future Therapies
Journal of Clinical Medicine Review Pathogenesis and Current Treatment of Osteosarcoma: Perspectives for Future Therapies Richa Rathore 1 and Brian A. Van Tine 1,2,3,* 1 Division of Medical Oncology, Washington University in St. Louis, St. Louis, MO 63110, USA; [email protected] 2 Division of Pediatric Hematology and Oncology, St. Louis Children’s Hospital, St. Louis, MO 63110, USA 3 Siteman Cancer Center, St. Louis, MO 63110, USA * Correspondence: [email protected] Abstract: Osteosarcoma is the most common primary malignant bone tumor in children and young adults. The standard-of-care curative treatment for osteosarcoma utilizes doxorubicin, cisplatin, and high-dose methotrexate, a standard that has not changed in more than 40 years. The development of patient-specific therapies requires an in-depth understanding of the unique genetics and biology of the tumor. Here, we discuss the role of normal bone biology in osteosarcomagenesis, highlighting the factors that drive normal osteoblast production, as well as abnormal osteosarcoma development. We then describe the pathology and current standard of care of osteosarcoma. Given the complex hetero- geneity of osteosarcoma tumors, we explore the development of novel therapeutics for osteosarcoma that encompass a series of molecular targets. This analysis of pathogenic mechanisms will shed light on promising avenues for future therapeutic research in osteosarcoma. Keywords: osteosarcoma; mesenchymal stem cell; osteoblast; sarcoma; methotrexate Citation: Rathore, R.; Van Tine, B.A. Pathogenesis and Current Treatment of Osteosarcoma: Perspectives for Future Therapies. J. Clin. Med. 2021, 1. Introduction 10, 1182. https://doi.org/10.3390/ Osteosarcomas are the most common pediatric and adult bone tumor, with more than jcm10061182 1000 new cases every year in the United States alone. -
The Health-Related Quality of Life of Sarcoma Patients and Survivors In
Cancers 2020, 12 S1 of S7 Supplementary Materials The Health-Related Quality of Life of Sarcoma Patients and Survivors in Germany—Cross-Sectional Results of A Nationwide Observational Study (PROSa) Martin Eichler, Leopold Hentschel, Stephan Richter, Peter Hohenberger, Bernd Kasper, Dimosthenis Andreou, Daniel Pink, Jens Jakob, Susanne Singer, Robert Grützmann, Stephen Fung, Eva Wardelmann, Karin Arndt, Vitali Heidt, Christine Hofbauer, Marius Fried, Verena I. Gaidzik, Karl Verpoort, Marit Ahrens, Jürgen Weitz, Klaus-Dieter Schaser, Martin Bornhäuser, Jochen Schmitt, Markus K. Schuler and the PROSa study group Includes Entities We included sarcomas according to the following WHO classification. - Fletcher CDM, World Health Organization, International Agency for Research on Cancer, editors. WHO classification of tumours of soft tissue and bone. 4th ed. Lyon: IARC Press; 2013. 468 p. (World Health Organization classification of tumours). - Kurman RJ, International Agency for Research on Cancer, World Health Organization, editors. WHO classification of tumours of female reproductive organs. 4th ed. Lyon: International Agency for Research on Cancer; 2014. 307 p. (World Health Organization classification of tumours). - Humphrey PA, Moch H, Cubilla AL, Ulbright TM, Reuter VE. The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs—Part B: Prostate and Bladder Tumours. Eur Urol. 2016 Jul;70(1):106–19. - World Health Organization, Swerdlow SH, International Agency for Research on Cancer, editors. WHO classification of tumours of haematopoietic and lymphoid tissues: [... reflects the views of a working group that convened for an Editorial and Consensus Conference at the International Agency for Research on Cancer (IARC), Lyon, October 25 - 27, 2007]. 4. ed. -
Chondroblastoma-Like Extraskeletal Chondroma of The
Scholars Journal of Applied Medical Sciences (SJAMS) ISSN 2320-6691 (Online) Sch. J. App. Med. Sci., 2014; 2(4D):1428-1430 ISSN 2347-954X (Print) ©Scholars Academic and Scientific Publisher (An International Publisher for Academic and Scientific Resources) www.saspublisher.com Case Report Chondroblastoma-Like Extraskeletal Chondroma of the Hand: A Rare Case Report Navya BN1*, Ranganath N2, Karumbaiah P3, Kariappa TM4 1Assistant Professor, Department of Pathology, KVG Medical College and Hospital, Kurunjibag, Sullia-574327, India 2Assistant Professor, Department of Orthopaedics, KVG Medical College and Hospital, Kurunjibag, Sullia-574327, India 3Associate Prof , Department of Pathology , KVG Medical College and Hospital, Kurunjibag, Sullia-574327, India 4Professor & HOD, Department of Pathology, KVG Medical College and Hospital, Kurunjibag, Sullia-574327, India *Corresponding author Dr. Navya BN Email: Abstract: Extraskeletal chondroma (ESC) is a rare benign cartilaginous tumor that occurs predominantly in soft tissues near small joints of hand and feet. The importance of this lesion is that it must be distinguished from more aggressive soft tissue chondrosarcoma so as to spare the patient from unnecessary radical therapy. Here, we present a case of ESC of hand in a 32 yr old female with a variable histological appearance exhibiting chondroblastoma- like areas leading to a mistaken diagnosis of Extraskeletal myxoid chondrosarcomas (ESMCS). Hence, the case had to be carefully evaluated to exclude ESMCS and to make the diagnosis of ESC. The treatment was limited to simple excision of the tumor and extensive surgery and radiotherapy was avoided. Keywords: Extraskeletal chondroma, chondroblastoma- like areas, Extraskeletal myxoid chondrosarcomas. INTRODUCTION Extraskeletal chondroma (ESC ) also called as chondroma of soft parts is a relatively rare, benign, slow-growing soft tissue tumor composed mainly of hyaline cartilage with no connection to bone or periosteum. -
Osteoid Osteoma: Contemporary Management
eCommons@AKU Section of Orthopaedic Surgery Department of Surgery 2018 Osteoid osteoma: Contemporary management Shahryar Noordin Aga Khan University, [email protected] Salim Allana Emory University Kiran Hilal Aga Khan University, [email protected] Riaz Hussain Lukhadwala Aga Khan University, [email protected] Anum Sadruddin Pidani Aga Khan University, [email protected] See next page for additional authors Follow this and additional works at: https://ecommons.aku.edu/pakistan_fhs_mc_surg_orthop Part of the Orthopedics Commons, Radiology Commons, and the Surgery Commons Recommended Citation Noordin, S., Allana, S., Hilal, K., Lukhadwala, R. H., Pidani, A. S., Ud Din, N. (2018). Osteoid osteoma: Contemporary management. Orthopedic Reviews, 10(3), 108-119. Available at: https://ecommons.aku.edu/pakistan_fhs_mc_surg_orthop/92 Authors Shahryar Noordin, Salim Allana, Kiran Hilal, Riaz Hussain Lukhadwala, Anum Sadruddin Pidani, and Nasir Ud Din This article is available at eCommons@AKU: https://ecommons.aku.edu/pakistan_fhs_mc_surg_orthop/92 Orthopedic Reviews 2018; volume 10:7496 Osteoid osteoma: Contemporary management Epidemiology Correspondence: Shahryar Noordin, Orthopaedic Surgery, Aga Khan University, Osteoid osteoma accounts for around Karachi, Pakistan. Shahryar Noordin,1 Salim Allana,2 5% of all bone tumors and 11% of benign Tel.: 021.3486.4384. 4 Kiran Hilal,3 Naila Nadeem,3 bone tumors. Osteoid osteoma is the third E-mail: [email protected] Riaz Lakdawala,1 Anum Sadruddin,4 most common biopsy analyzed benign bone 5 tumor after osteochondroma and nonossify- Key words: Osteoid osteoma; tumor; benign; Nasir Uddin imaging; pathogenesis; management. 1 ing fibroma. Two to 3% of excised primary Orthopaedic Surgery, Aga Khan bone tumors are osteoid osteomas.5 Males University, Karachi, Pakistan; Contributions: SN, SA, study design, data col- are more commonly affected with an lection, manuscript writing; KH, NU, data col- 2 5 Department of Epidemiology, Rollins approximate male/female ratio of 2 to 1. -
Chondroblastoma in Dog – a Rare Case
International Journal of Science and Research (IJSR) ISSN (Online): 2319-7064 Index Copernicus Value (2015): 78.96 | Impact Factor (2015): 6.391 Chondroblastoma in Dog – A Rare Case 1, 2 N. G. Amith B. N. Nagaraja Department of Surgery and Radiology, Veterinary College, Hebbal, Bangalore-24 1Veterinary Surgeon, Charlie’s animal Rescue Centre, Jakkur , Bangalore – 32, India 2Professors, Department of Veterinary Surgery and Radiology, KVAFSU, Veterinary College, Bangalore-24, India Abstract: Chondroblastoma (CB) is a rare benign chondral tumour characterised by an epiphyseal location in long bones. A four year old Rottweiler male dog was presented with the history of limping on right fore limb and swelling since two weeks as seen by owner. A plain radiograph showed a well-defined lytic defect, measuring 4-5 cm in diameter in the proximal epiphysis of the right ulnar region. The bone biopsy sample was collected and send for laboratory analysis for histopathology. Keywords: Chondroblastoma, dogs, long bone 1. Introduction Benign cartilage tumours of bone are the most common benign primary bone tumours and include osteochondroma, (en)chondroma, periosteal chondroma, chondroblastoma and chondromyxoid fibroma (Douis and Saifuddin, 2012). Chondroblastoma is a cancer composed of cells derived from transformed cells that produce cartilage and uncommon benign bone tumor arising from a secondary ossification center in the epiphyseal plates and apophyses. It is estimated to represent less than 1% of all primary bone tumours (Douis and Saifuddin, 2012). More than 75% of chondroblastoma lesions involve the long bones, and the most common anatomic sites are the epiphyseal and epimetaphyseal regions of the distal and proximal femur, proximal tibia, and proximal humerus (Turcotte et al.,1993) 2. -
Leg Pain and Swelling in a 22-Year-Old Man
CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Number 448, pp. 259–266 © 2006 Lippincott Williams & Wilkins Orthopaedic • Radiology • Pathology Conference Leg Pain and Swelling in a 22-Year-Old Man Mustafa H. Khan, MD*; Ritesh Darji, MD†; Uma Rao, MD‡; and Richard McGough, MD* HISTORY AND PHYSICAL EXAMINATION which precluded him from participating in any sports, and night pain. The patient localized the pain over the anterior The patient was a 22-year man who presented with right aspect of the midtibia. He denied any history of trauma. He leg pain and swelling that had increased during the last 6 required regular doses of oxycodone for the past year to years. He complained of pain with walking and running, achieve adequate pain relief. His past medical history was unremarkable. From the *Departments of Orthopedic Surgery, †Radiology, and ‡Pathology; On physical examination a large anterior pretibial bony University of Pittsburgh Medical Center, Pittsburgh, PA. mass was palpable. No other masses were palpable in the Each author certifies that he or she has no commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrange- extremities and there was no evidence of lymphadenopa- ments, etc) that might pose a conflict of interest in connection with the thy. Active and passive range of motion testing and neu- submitted article. rovascular examination was in normal limits. Each author certifies that his or her institution has approved the reporting of this case report and that all investigations were conducted in conformity with Plain radiographs and MRI scans of the leg, along ethical principles of research. with CT scan of the leg and chest, were obtained Correspondence to: Richard McGough, MD, Department of Orthopedic Sur- (Figs 1–3).