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. 2019 Jan 30;9:973. doi: 10.1038/s41598-018-37801-2

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Pathological findings in canine hypophosphatasia. (a) A cross section of a formalin fixed femur from a 3-month-old affected puppy (litter 1). The femur has a striking hourglass appearance. The diaphyseal periosteum and cortex are abnormally broadened by unmineralized osteoid and fibrous tissue, and the marrow cavity is narrowed due to defective modelling of primary spongiosa (encircled). Retained epiphyseal cartilage (open arrowhead) and irregular growth lines (arrowhead) are seen within the epiphyseal areas. (b) Formalin-fixed cerebellum of a 2-week-old affected puppy (litter 2). The cerebellar vermis is protruding into the spinal canal (arrowhead). (c) Longitudinal section of diaphyseal cortex, decalcified, HE 50X. The periosteal cambium (C) is thickened and cellular, with an underlying broad zone of unmineralized woven bone (W) and a cortex consisting of lamellar bone (L) instead of compact bone. The periosteal fibrous layer (F) appears normal. (d) Articular cartilage and epiphysis, decalcified, HE 50X. The ossification front is uneven (line) and irregular tongues of retained poorly mineralized cartilage (arrowheads) are present within the epiphysis. (e) Thyroid gland from an affected puppy, HE 200X. The C-cells are numerous and hypertrophic between the colloid follicles. (f) Thyroid gland from an affected puppy, calcitonin IHC 200X. Profound C-cell hypertrophy and hyperplasia is noted. (g) Thyroid gland of an unaffected, age- and gender matched puppy, calcitonin IHC 200X. A few C-cell groups and scattered single calcitonin-rich C-cells are seen. All histopathological images (c–g) are from the 3-month-old affected puppy (litter 1).