BackgroundThe inhibitor of apoptosis (IAP) protein Survivin and its splice variants are differentially expressed in breast cancer tissues. Our previous work showed Survivin is released from tumor cells via small membrane-bound vesicles called exosomes. We, therefore, hypothesize that analysis of serum exosomal Survivin and its splice variants may provide a novel biomarker for early diagnosis of breast cancer.MethodsWe collected sera from forty breast cancer patients and ten control patients who were disease free for 5 years after treatment. In addition, twenty-three paired breast cancer tumor tissues from those same 40 patients were analyzed for splice variants. Serum levels of Survivin were analyzed using ELISA and exosomes were isolated from this serum using the commercially available ExoQuick kit, with subsequent Western blots and immunohistochemistry performed.ResultsSurvivin levels were significantly higher in all the breast cancer samples compared to controls (p < 0.05) with exosome amounts significantly higher in cancer patient sera compared to controls (p < 0.01). While Survivin and Survivin-∆Ex3 splice variant expression and localization was identical in serum exosomes, differential expression of Survivin-2B protein existed in the exosomes. Similarly, Survivin and Survivin-∆Ex3 proteins were the predominant forms detected in all of the breast cancer tissues evaluated in this study, whereas a more variable expression of Survivin-2B level was found at different cancer stages.ConclusionIn this study we show for the first time that like Survivin, the Survivin splice variants are also exosomally packaged in the breast cancer patients’ sera, mimicking the survivin splice variant pattern that we also report in breast cancer tissues. Differential expression of exosomal-Survivin, particularly Survivin-2B, may serve as a diagnostic and/or prognostic marker, a “liquid biopsy” if you will, in early breast cancer patients. Furthermore, a more thorough understanding of the role of this prominent antiapoptotic pathway could lead to the development of potential therapeutics for breast cancer patients.

Congenital granular cell epulis is a rarely reported lesion of unknown histogenesis with a strong predilection for the maxillary alveolar ridge of newborn girls. Microscopically, it demonstrates nests of polygonal cells with granular cytoplasm, a prominent capillary network, and attenuated overlying squamous epithelium. The lesion lacks immunoreactivity for S-100, laminin, chromogranin, and most other markers except neuron-specific enolase and vimentin. Through careful observation of its unique clinical, histopathologic, and immunohistochemical features, this lesion can be distinguished from the more common adult granular cell tumor as well as other differential diagnoses.

Presence of ENE on SLN dissection is associated with N2 disease. Despite increased nodal burden, patients with 1 or 2 positive SLNs and ENE 2 mm or smaller demonstrated recurrence and survival rates similar to those of patients without ENE. Reporting of ENE size should be standardized and required.

Background The purpose of this study was to evaluate our surgical experience in patients with primary hyperparathyroidism (PHPT) with nonlocalizing sestimibi and ultrasound scans. Methods A retrospective review of 521 patients treated from April 2005 to July 2017 at Loma Linda University Medical Center who received parathyroidectomy for PHPT. One hundred forty‐seven patients (28%) had double negative localization (nonlocalizing sestamibi and ultrasound). Results Surgical cure for PHPT was 97.3% and 99.2% with nonlocalized and localized disease, respectively, and complication rates were similar between groups. Preoperative parathyroid hormone and gland weight were significantly lower with nonlocalization. The incidence of multigland disease (MGD) was greater in patients with nonlocalization on sestamibi and ultrasound. Conclusion Nonlocalization of parathyroid glands was not associated with decreased cure rate or increased morbidity. The presence of MGD and requirement for more extensive surgery were greater in patients with nonlocalizing disease.

Enigma may serve as an oncoprotein marker, identifying benign from malignant thyroid tissue on FNA. Enigma may have a role in carcinogenesis of thyroid cancer independent of tissue calcification, possibly in relation to interaction with BMP-1.