It has been widely accepted that programmed cell death (PCD) is an essential event in palatogenesis and that its failure can result in cleft palate, one of the most common birth defects in the human. However, some conflicting results have been reported concerning the timing of cell death occurring in the fusing palate and therefore the role of PCD in palatal fusion is controversial. In order to clarify whether cell death is indispensable for mammalian palatogenesis, we cultivated the palates of day-13 mouse fetuses in vitro and prevented cell death by treating them with the inhibitors of caspases-1 and -3 or with aurintricarboxylic acid which inhibits the activity of caspaseactivated DNase. Even when cell death was almost completely inhibited, palatal fusion took place successfully. Histological examination revealed that in the absence of apoptotic cell death, the medial edge epithelia of opposing palatal shelves adhered to each other and subsequently, the midline epithelial seam was disrupted and disappeared to bring about mesenchymal confluence across the palate. It seems that cell death is not a necessary prerequisite for palatal fusion but it may help to efficiently eliminate unnecessary cells which failed to migrate or differentiate properly.

Day-13 fetal mouse palates (plug day=day 0) were labeled with carbon particles at various sites of palatal shelves and cultivated in a chemically defined medium for up to 48 h. During the culture period, the bilateral palatal shelves came in contact and fused with each other, which simulated in vivo palatogenesis. The carbon study revealed that at the midpalatal region, the medial edge of the palatal shelf elevated to the horizontal plane, elongated toward the midline, and made contact with the medial edge of the opposing shelf. On the other hand, near the anterior and posterior ends of the shelf, some new tissue was formed at the medial edge of the shelf by remodeling and this newly formed tissue took part in palatal fusion. The results of the present study indicate that during mouse palatogenesis, the anterior and posterior regions of the palatal shelf behave differently from the midpalatal region. It seems that in the fetal mouse palate, the midpalate closes mainly by means of rotation and medial elongation of the shelf, whereas the anterior and posterior parts of the palate close mainly by tissue remodeling of the medial edge and partly by medial elongation of the shelf.

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Fibroadenoma is the most common form of benign breast tumor and the most common breast tumor in women under 30 years of age. However, carcinoma arising within a fibroadenoma is unusual, with over 100 cases reported in the literature. Histological diagnosis is typically unexpected. A 46-year-old female with no family history of breast malignancies was admitted for an elastic hard lump in the upper-outer quadrant of her right breast. At a clinic that she visited previously, her condition was diagnosed by core needle biopsy with four specimens showing fibroadenoma with borderline atypical ductal hyperplasia at pathology. Excisional biopsy was recommended for pathological diagnosis. The patient requested a definitive diagnosis and alternative treatment to tumorectomy. More biopsy specimens were needed for pathological diagnosis; therefore, ultrasonography-guided vacuum-assisted core needle biopsies were obtained, confirming ductal carcinoma in situ with questionable microinvasion of intracanalicular- and pericanalicular-type fibroadenoma. Right breast-conserving surgery and sentinel lymph node biopsy were immediately performed for radical therapy. We present this case to increase awareness of this entity and stress the need for histological evaluation of some breast masses.

We report a case of non-bacterial cystitis that occurred after administration of atezolizumab, an antibody against programmed cell death ligand 1 (PD-L1). This cystitis was considered an immune-related adverse event (irAE). A 67-year-old woman with advanced breast cancer (cT4bN1M1, cStage IV) was treated with atezolizumab and nanoparticle albumin-bound (nab) paclitaxel. She consulted a physician for urethral pain and frequent urination during the fourth cycle of treatment. Cystitis symptoms were not relieved by antibiotic treatment and worsened. The results of her urine culture and cytology were negative for malignancy. Cystoscopy showed diffuse redness of the bladder mucosa. A bladder biopsy revealed no evidence of malignancy. Since the patient’s symptoms resolved with steroid therapy, urethral pain and frequent urination associated with atezolizumab were considered to be irAE by the diagnosis of exclusion. After immunostaining of the bladder biopsy sections, high PD-L1 expression was detected in the urothelium, which could explain the cause of irAE.