CE Directed Reading Multiple Hereditary Exostoses Cheryl O DuBose, EdD, R.T.(R)(CT)(MR)(QM) Multiple hereditary exostoses After completing this article, the reader should be able to: (MHE), also known as Define terms such as exostosis, osteochondroma, and chondrosarcoma. multiple osteochondromas, Describe the basic characteristics of multiple hereditary exostoses (MHE). is an autosomal dominant Discuss the genetic components of MHE. disease that results in Explain the roles of various imaging modalities in the diagnosis of osteochondromas the development of and chondrosarcomas. Discuss treatment options and prognosis for those affected by MHE. osteochondromas throughout the body. The disease typically is diagnosed during ultiple hereditary exostoses direction in bone growth (eg, Nora childhood and requires lifelong (MHE) is a rare bone disor- lesion or Trevor disease), or a reactive monitoring and treatment der that affects the growth process (subungual exostosis).4 This of painful osteochondromas. plates or other areas of the clarification of terminology allows Individuals with MHE must M body in which cartilage eventually con- for a more specific diagnosis. Other be monitored for complications verts to bone.1,2 Approximately 96% of terms often are used to describe MHE that can arise and the potential MHE diagnoses occur in individuals (see Box 1).1,5,6 malignant transformation between 2 and 12 years old.1 Ty pically Although the World Health of an osteochondroma into involving long bones, this disease Organization reclassified MHE as a chondrosarcoma. This results in sometimes painful, abnormal multiple osteochondromas, a review of article discusses the basic bone growth that can adversely affect the literature shows that MHE remains characteristics of MHE, the knees, forearms, humerus, pelvis, a popular description of the disease 1,3 3,6-9 genetic links, the role of ribs, or spine. MHE produces numer- process. MHE is the term used in medical imaging in diagnosis, ous benign tumors that vary in size and this article to reflect popular medical and treatment options. shape, and usually are persistent, even literature from the United States and a recurring in an area following surgical cited case study. resection.1 Genetic mutations are thought to cause MHE.3 Normal Bone Anatomy MHE was reclassified as multiple To understand the significance of This article is a Directed osteochondromas by the World Health abnormal bone growth in patients 1,2 Reading. Your access to Organization in 2002. The explana- with MHE, it is necessary to review Directed Reading quizzes tion for the change was the use of the normal bone anatomy and the bone for continuing education term exostosis by the medical commu- growth process. Bone is composed of credit is determined by nity and the public to describe any type 2 types of osseous tissue: cortical bone your membership status of bone growth, whether the growth and cancellous bone. Cortical bone and CE preference. was the result of a benign cartilaginous (also known as compact bone) is the tumor (osteochondroma), a distorted outermost layer of bone and contains RADIOLOGIC TECHNOLOGY, January/February 2016, Volume 87, Number 3 305 CE Directed Reading Multiple Hereditary Exostoses elementary units called osteons (or Haversian systems). Box 1 Osteons surround the Haversian canals, which carry Alternative Names for Multiple blood vessels, lymph vessels, and nerves throughout Hereditary Exostoses1,5,6 the cortical bone. The inside surface of cortical bone The following synonyms for multiple heredity exostoses often contains bone-forming cells (osteoblasts) and bone- are used in practice and in the literature: resorbing cells (osteoclasts). The dense cortical bone is Chondral osteogenic dysplasia of direction protected by the periosteum, a thin connective tissue Chondral osteoma membrane that covers and protects the entire bone and Deforming chondrodysplasia also contains osteoblasts, fibroblasts, blood vessels, and Diaphyseal aclasis (multiple hereditary) 10,11 nerves (see Figure 1). Dyschondroplasia The medullary cavity is within the cortical bone Exostosing disease 10,11 and is composed of cancellous, or spongy, bone. Exostotic dysplasia Cancellous bone is less dense than cortical bone, con- EXT sists of trabeculae, is responsible for hematopoiesis Hereditary deforming chondrodysplasia (blood formation), and is found in the bony interior and Hereditary multiple exostoses at the epiphyses of long bones.11 The epiphyseal plate Osteochondromatosis and the adjacent terminal diaphysis represent the most Osteogenic disease Multiple cartilaginous exostoses Multiple congenital osteochondromata Multiple osteochondromas Multiple osteomatoses Figure 1. Internal bone structure. 306 RADIOLOGIC TECHNOLOGY, January/February 2016, Volume 87, Number 3 CE Directed Reading DuBose metabolically active segment of the long bones until a ■ Calcium deposits in various organs throughout child reaches puberty, unless trauma or another patho- the body (especially the kidneys). physiological condition, such as healing of bone frac- ■ Renal failure. tures, occurs.10 This area also is known as the metaphy- ■ Anemia. sis because of its changing nature during growth and ■ Leukopenia. development.10 It is the abnormal osseous transforma- ■ Osteoporosis. tion of the cartilage cap in the diaphysis, the shaft of ■ Bone fractures. the long bones of the axial and appendicular skeleton, Chemotherapy and radiation therapy are the stan- that is the primary negative outcome for patients with dard methods of treatment, but the prognosis for this MHE.9 Yellow bone marrow is housed within the disease is grim. Most individuals survive 3 to 4 years, diaphysis, and the body can convert it to red marrow in but few survive beyond 10 years.10,11 cases of heavy blood loss or anemia to increase blood cell production.11 Leukemia Discovered in 1845 almost simultaneously by Bone Tumors Rudolf Virchow in Berlin and John Hughes Bennett in Primary bone tumors are rare, accounting for fewer Edinburgh, leukemia is a malignant disease involving than 1% of all clinically diagnosed tumors.10 Of these, white blood cells in the bone marrow and peripheral approximately 50% result from neoplasms of the blood- blood.10 White blood cells are produced by flat bones, forming cells of the bone marrow, such as multiple such as the sternum and pelvis, and by lymph nodes myeloma and leukemia. The other 50% of primary bone in adults because the blood-producing red bone mar- tumors are the result of bone-forming cells (osteoid row of long bones is replaced by fat as people mature. osteoma and osteosarcoma), cartilage cells (chondroma However, during infancy and adolescence, white blood and chondrosarcoma), osteoclasts, and primitive mes- cells can be produced by the thymus, lymph nodes, long enchymal bone marrow cells (Ewing sarcoma).10 bones, or flat bones. In cases where hematopoietic bone marrow is destroyed, hematopoiesis might resume in Primary Bone Tumors the spleen, liver, and lymph nodes.10 Multiple Myeloma The term leukemia means “white blood,” referring to Multiple myeloma is a malignant disease of plasma the milky white appearance of blood when the number cells. Plasma accounts for approximately 55% to 60% of white cells reaches approximately 1 million cells/L. of total blood volume and 5% of cells found in healthy However, with modern medicine, most patients are diag- bone marrow. Descendants of B lymphocytes, plasma nosed and treated for the disease well before white cell lev- cells proliferate and produce antibodies in the form els progress to this point. Symptoms of leukemia include of various immunoglobins. Multiple myeloma is the anemia, recurrent infections, and uncontrollable bleeding. result of a malignant transformation of a single plasma According to Damjanov, overwhelming infection is the cell, which is known as plasmacytoma.10 In plasmacy- leading cause of death in all forms of leukemia.10 toma, the malignantly transformed bone marrow cell produces numerous clones with the same mutation Osteoid Osteoma that spread to other sites and become multiple myelo- Osteoid osteomas are benign bone tumors repre- ma.10,11 As the number of immunoglobulins specific to senting approximately 10% of benign skeletal neo- the plasmacytoma increases, a spike in the abnormal plasms12 that usually affect the long bones of young plasma cell mutation can be detected through serum adults.13 Small and spherical in shape, these tumors protein testing.10 typically have a diameter of 1.5 cm or less.12 Although Multiple myeloma eventually destroys bone marrow an osteoma can appear anywhere in the skeletal system, and the surrounding bone, creating multiple lytic bone the lesion usually is seen in the long bones of the lower lesions that appear on radiographs.10,11 Complications extremities. Approximately one-quarter of these lesions include10,11: occur in the proximal femur.12 RADIOLOGIC TECHNOLOGY, January/February 2016, Volume 87, Number 3 307 CE Directed Reading Multiple Hereditary Exostoses Pain and swelling of the affected area, as well as Chondrosarcomas typically originate in the axial possible restriction of motion, are the most common skeleton (pelvis, ribs, and vertebrae) and the adjacent clinical symptoms. Diagnosis generally is supported portion of long bones (proximal femur and humer- by radiography, computed tomography (CT), or us). 10,11 Patients might describe a dull pain of long magnetic resonance (MR) imaging.12 Bone scintig- duration, an increase in the