**2. A familial canine thyroid carcinoma**

Reports of hereditary thyroid carcinoma in dogs are limited. One report presented a hereditary canine MTC with a potential dominant inheritance of autosomal or X-linked inheritance in a family of a mixed dog breed with Alaskan malamute as a major influence [11]. We reported a hereditary thyroid follicular cell carcinoma in a large number of Dutch German longhaired pointer (GLP) dogs [3]. Over the past ~20 years, thyroid tumor was identified in 84 Dutch GLPs. Among those affected GLPs, 54 had histologically diagnosed thyroid follicular cell carcinomas (FCCs), 29 were suspected cases solely based on clinical diagnosis (such as palpable mass in the neck), and 1 had thyroid adenoma. The identified histology subtypes of the FCC include FTC, CTC, FCTC, PTC, and carcinosarcoma. The same as findings in other studies about canine thyroid tumor [1], FTC is the most common among all these subtypes, accounting for 46%. Meanwhile, no sex predisposition was observed in those affected GLPs. Canine FTC

#### **Figure 1.**

*Pedigree of dogs related to two dogs (pointed by red arrows) that were intensively used in breeding [3]. Forty-five histopathologically confirmed affected dogs are closely related to these two dogs. Circles represent females, and squares represent males. Dot line shows identical dogs. Affected dogs with histological diagnosis are highlighted in red, and suspected affected dogs (without histopathology diagnosis) are in black, whereas unaffected dogs remain white. A question mark represents the dogs with unknown status.*

incidence increases with age where approximately 57% of cases were diagnosed at ages between 10 and 15 years. However, FCCs in these GLPs were diagnosed earlier where 76% of cases were diagnosed before 10 years of age.

These affected GLPs are very closely related in terms of genetic relationship, where many of them are first-degree relatives, suggesting that these FCCs belong to a familial form of thyroid carcinoma (**Figure 1**). In humans, a hereditary thyroid cancer is diagnosed when there are two or more first-degree relatives affected [12]. In dogs, according to authors' knowledge, there is no definition of a hereditary thyroid cancer yet. The definition of hereditary thyroid carcinoma in humans can be borrowed. A striking high incidence of the FCC in offspring of two GLPs was seen (**Figure 1**). Most of identified affected dogs are related to these two GLPs in pedigree. In the past, in dog breeding, some prominent dogs were used intensively including breeding with relatives, which resulted in the introduction of genetic defects and spread unwanted diseases in the population. The familial FCC here is a good example.
