First description of feline inflammatory mammary carcinoma: clinicopathological and immunohistochemical characteristics of three cases

INTRODUCTION: Inflammatory breast cancer is a special type of locally advanced mammary cancer that is associated with particularly aggressive behaviour and poor prognosis. The dog was considered the only natural model in which to study the disease because, until now, it was the only species known to present with inflammatory mammary carcinoma (IMC) spontaneously. In the present study we describe clinicopathological and immunohistochemical findings of three cats with IMC, in order to evaluate its possible value as an animal model. METHODS: We prospectively studied three female cats with clinical symptoms of IMC, identified over a period of 3 years. Clinicopathological and immunohistochemical evaluations of Ki-67, and oestrogen, progesterone and androgen receptors were performed. RESULTS: All three animals presented with secondary IMC (postsurgical) characterized by a rapid onset of erythema, severe oedema, extreme local pain and firmness, absence of subjacent mammary nodules, and involvement of extremities. Rejection of the surgical suture was observed in two of the cats. Histologically, highly malignant papillary mammary carcinomas, dermal tumour embolization of superficial lymphatic vessels, and severe secondary inflammation were observed. The animals were put to sleep at 10, 15 and 45 days after diagnosis. Metastases were detected in regional lymph nodes and lungs in the two animals that were necropsied. All tumours had a high Ki-67 proliferation index and were positive for oestrogen, progesterone and androgen receptors. CONCLUSION: Our findings in feline IMC (very low prevalence, only secondary IMC, frequent association of inflammatory reaction with surgical suture rejection, steroid receptor positivity) indicate that feline IMC could be useful as an animal model of human inflammatory breast cancer, although the data should be considered with caution

The Arabidopsis plastid-signalling mutant gun1 (genomes uncoupled1) shows altered sensitivity to sucrose and abscisic acid and alterations in early seedling development

Developing seedlings of the Arabidopsis gun1 (genomes uncoupled1) mutant, which is defective in retrograde plastid-to-nucleus signalling, show several previously unrecognized mutant phenotypes. gun1 seedlings accumulated less anthocyanin than wild-type seedlings when grown in the presence of 2% (w/v) sucrose, due to lower amounts of transcripts of early anthocyanin biosynthesis genes in gun1. Norflurazon and lincomycin, which induce retrograde signalling, further decreased the anthocyanin content of sucrose-treated seedlings, and altered the temporal pattern of anthocyanin accumulation. Lincomycin treatment altered the spatial pattern of sucrose-induced anthocyanin accumulation, suggesting that plastids provide information for the regulation of anthocyanin biosynthesis in Arabidopsis seedlings. The temporal pattern of accumulation of LHCB1 transcripts differed between wild-type and gun1 seedlings, and gun1 seedlings were more sensitive to sucrose suppression of LHCB1 transcript accumulation than wild-type seedlings. Growth and development of gun1 seedlings was more sensitive to exogenous 2% sucrose than wild-type seedlings and, in the presence of lincomycin, cotyledon expansion was enhanced in gun1 seedlings compared to the wild type. gun1 seedlings were more sensitive than wild-type seedlings to the inhibition of seedling growth and development by abscisic acid. These observations clearly implicate GUN1 and plastid signalling in the regulation of seedling development and anthocyanin biosynthesis, and indicate a complex interplay between sucrose and plastid signalling pathways

POLR3B is associated with a developmental and epileptic encephalopathy with myoclonic‐atonic seizures and ataxia

Objective: POLR3B encodes the second largest subunit of RNA polymerase III, which is essential for transcription of small non-coding RNAs. Biallelic pathogenic variants in POLR3B are associated with an inherited hypomyelinating leukodystrophy. Recently, de novo heterozygous variants in POLR3B were reported in six individuals with ataxia, spasticity, and demyelinating peripheral neuropathy. Three of these individuals had epileptic seizures. The aim of this article is to precisely define the epilepsy phenotype associated with de novo heterozygous POLR3B variants. Methods: We used online gene-matching tools to identify 13 patients with de novo POLR3B variants. We systematically collected genotype and phenotype data from clinicians using two standardized proformas. Results: All 13 patients had novel POLR3B variants. Twelve of 13 variants were classified as pathogenic or likely pathogenic as per American College of Medical Genetics (ACMG) criteria. Patients presented with generalized myoclonic, myoclonic-atonic, atypical absence, or tonic-clonic seizures between the ages of six months and 4 years. Epilepsy was classified as epilepsy with myoclonic-atonic seizures (EMAtS) in seven patients and “probable EMAtS” in two more. Seizures were treatment resistant in all cases. Three patients became seizure-free. All patients had some degree of developmental delay or intellectual disability. In most cases developmental delay was apparent before the onset of seizures. Three of 13 cases were reported to have developmental stagnation or regression in association with seizure onset. Treatments for epilepsy that were reported by clinicians to be effective were: sodium valproate, which was effective in five of nine patients (5/9) who tried it; rufinamide (2/3); and ketogenic diet (2/3). Additional features were ataxia/incoordination (8/13); microcephaly (7/13); peripheral neuropathy (4/13), and spasticity/hypertonia (6/13). Significance: POLR3B is a novel genetic developmental and epileptic encephalopathy (DEE) in which EMAtS is the predominant epilepsy phenotype. Ataxia, neuropathy, and hypertonia may be variously observed in these patients