Nikiforov YE, Seethala RR, Tallini G, et al: Nomenclature revision for encapsulated follicular variant of papillary thyroid carcinoma: a paradigm shift to reduce overtreatment of indolent tumors, JAMA Oncol 2:1023–1029, 2016. [The defining paper that led to changing the nomenclature for the erstwhile entity known as encapsulated follicular variant of papillary thyroid carcinoma. This paper is also important to understand the concept of “overdiagnosis,” which is increasingly becoming a factor due to increasing use of imaging modalities in patients.]
Pociot F, Lernmark A: Genetic risk factors for type 1 diabetes, Lancet 387:2331–2339, 2016. [A recent review on the complex genetics of type 1 diabetes, especially the HLA alleles, and how these might interface with the environment.]
Tuomi T, Santoro N, Caprio S, et al: The many faces of diabetes: a disease with increasing heterogeneity, Lancet 383:1084–1094, 2014. [An excellent review underscoring the etiologic heterogeneity of the entity that we know as “diabetes”—and how so many diverse genetic and environmental factors contribute to the phenotype of hyperglycemia.]
Zheng S, Cherniack AD, Dewal N, et al: Comprehensive pan-genomic characterization of adrenocortical carcinoma, Cancer Cell 29:723– 736, 2016. [The definitive study from The Cancer Genome Atlas (TCGA] on genomics of adrenocortical cancers.] http://ebooksmedicine.net studentconsult.com
Bones, Joints, and Soft
Healing of Fractures
Tumors of Unknown Origin
The functions of bone include mechanical support, transmission of forces generated by muscles, protection of viscera, mineral homeostasis, and providing a niche for the production of blood cells. The constituents of bone include an extracellular matrix and specialized cells responsible for production and maintenance of the matrix.
Bone matrix is composed of an organic component known as osteoid (35%) and a mineral component (65%). Embedded within the bone matrix are a variety of bone cells including osteocytes that lay down bone and osteoclasts that reabsorb bone. These two cells types maintain bone homeostasis. Osteoid is made up predominantly of type I collagen with smaller amounts of glycosaminoglycans and other proteins. The unique feature of bone matrix, its hardness, is imparted by the inorganic moiety hydroxyapatite (Ca10[PO4]6[OH]2). The bone matrix is synthesized in one of two histologic forms, woven or lamellar (Fig. 21.1 ). Woven bone is produced rapidly, such as during fetal development orfracturerepair,butthehaphazardarrangementofcollagen fibers imparts less structural integrity than the parallel collagen fibers in slowly produced lamellar bone. In an adult, the presence of woven bone is always abnormal, but it is not specific for any particular bone disease. A cross section of a typical long bone shows a dense outer cortex and a central medulla composed of bony trabeculae separated by marrow.
Bone contains three major cell types: • Osteoblasts, located on the surface of the matrix, synthesize, transport and assemble bone matrix and regulate its mineralization (
Fig. 21.2A ). They are derived from mesenchymal stem cells that are located under the periosteum in the developing bone and additionally in the medullary space later in life.
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Fig.21.1Wovenbone(A)ismorecellularanddisorganizedthanlamellarbone(B).