Tumor P70S6K hyperactivation is inversely associated with tumor-infiltrating lymphocytes in triple-negative breast cancer.

PURPOSE: Triple-negative breast cancer (TNBC) is characterized by large heterogeneity and relative lack of available targeted therapies. To find therapeutic strategies for distinct patients with TNBC, several approaches have been used for TNBC clustering, including recently immune and phosphoproteomic patterns. Based on 70-kDa ribosomal protein S6 kinase (P70S6K)-TNBC clustering, the current study explores the immune profiling in TNBC tumors. METHODS: Stromal tumor-infiltrating lymphocytes (sTILs) were evaluated in human TNBC tumor samples. Furthermore, immunohistochemistry staining for CD8, CD4, Foxp3, and CD20 was performed in tissue microarrays (TMA) sections. RESULTS: Histological analysis showed decreased sTILs, CD20+ cells, and CD8+/CD4+ ratio in high phosphorylated P70S6K (p-P70S6K) tumors. Moreover, p-P70S6K score was directly correlated with CD4+ and Foxp3+ T cells, while it was inversely correlated with CD8+/CD4+ and CD8+/Foxp3+ ratios. CONCLUSION: sTIL infiltration and lymphocyte profiling vary in the context of hyperactivation of P70S6K in TNBC tumors.

Oxyphil cells in primary hyperparathyroidism: a clinicopathological study.

BACKGROUND: The role of oxyphil cells (OxC) in primary hyperparathyroidism (PHPT) still remains controversial. Historically, they were believed to be involuted cells. However, they could play an important role in hormone secretion. The clinical behavior of OxC-rich adenomas and preoperative PHPT localization tests have been widely studied. The aim of this study is to analyze the implications of OxC in PHTP. METHODS: A retrospective cohort study of patients undergoing parathyroidectomy for PHPT was conducted. Additionally, we included normal glands removed in the context of PHPT or inadvertently during a thyroidectomy. All glands were reviewed independently by three researchers, performing a semi-quantitative analysis of the percentage of OxC. Groups with < 25% OxC and > 75% OxC were compared. RESULTS: In the period 2010-2017, 238 patients and 261 removed glands were included (8.8% OxCA > 75%). There were no differences in symptomatology and levels of preoperative calcium, parathormone, or 25-OH vitamin. Patients with OxCA > 75% had worse preoperative glomerular filtration rate (81.2 vs. 69.7 mL/min/1.73 m2; p = 0.043). They also had a trend towards larger size and weight (17 vs. 20 mm, p = 0.135 and 562 vs. 875 mg, p = 0.495), while ultrasound was found to have better accuracy (48.3% vs. 73.7%; p = 0.035). There were no normal glands with a content of OxC > 75%. CONCLUSIONS: Our study suggests that phosphocalcic metabolism is not influenced by the presence of a high content of OxC in the parathyroid glands. A high content of OxC seems to be exclusive to pathologic glands and could be related to the deterioration of renal function in patients with PHPT.

Fine needle aspiration cytology of a myxoid adrenocortical adenoma. A case report.

The myxoid variant of adrenocortical (AC) tumors is characterized by peculiar histologic features that differ from conventional ones. It shows a prominent myxoid stromal component and is composed of small cells with mild atypia arranged in cords, pseudoglandular structures and microcysts. Reflecting the rarity of this variant, very few cytologic descriptions are available. We describe one case in a 41-year-old woman with a previous diagnosis of breast carcinoma and BRCA1 mutation. During follow-up controls, an adrenal tumor was discovered. Fine needle aspiration cytology and Tru-Cut biopsies were performed simultaneously. Smears showed numerous groups of cohesive cells of intermediate to small size. Within the largest groups, aggregates of myxoid metachromatic material were evident. This myxoid material could also be observed as isolated acellular fragments. While the cytoplasm of most tumoral cells was homogenously stained some showed small vacuoles. Histologically, the tumor grew, forming anastomosing cords, separated by myxoid material that determined microcystic spaces. Immunohistochemistry was characteristic of AC myxoid tumor. After surgery, pathologic analysis confirmed this diagnosis. The tumor showed no necrosis or invasion, had a low mitotic index (3/50 high power fields) and Ki-67 proliferative index of 15%. According to the different diagnostic systems the tumor was classified as an adenoma. In conclusion, the myxoid variant of AC tumors shows peculiar cytologic features. If unaware of the existence of this variant, it can easily be misinterpreted as a metastatic tumor.

Cauterization of the germinal nail matrix using phenol applications of differing durations: a histologic study.

BACKGROUND: Phenol has been used for more than 60 years in the treatment of ingrown toenails. Many reports have documented the safety and effectiveness of phenol matricectomy, although with variable treatment application times. OBJECTIVE: We performed research to determine the application time required for phenol matricectomy for complete denaturation of the nail matrix to occur at a concentration of 88%. Identifying the optimal time required to destroy the germinal matrix without causing further soft-tissue damage should reduce the potential for complications. METHODS: Thirty anatomic cadaveric fresh hallux samples were used to perform phenol matricectomy. The applications were for 1 to 6 minutes using 10 samples per time point and analyzed by hematoxylin-eosin staining to determine the presence or absence of the basal or germinal layer of the nail bed epithelium (NBE). RESULTS: After a 1-minute application of 88% phenol solution, only superficial damage to the NBE was noted, with the basal layer primarily intact. After a 2-minute application, the nail plate was avulsed with a thin basal layer remaining. After a 3-minute application, full-thickness necrosis of the NBE was noted in 6 of the 10 specimens. After 4-, 5-, and 6-minute applications, full-thickness necrosis of the NBE was noted and the basal layer was completely destroyed in all 30 specimens. LIMITATIONS: The study was performed in cadaveric fresh specimens. CONCLUSIONS: Application of 88% phenol solution for at least 4 minutes is necessary for complete destruction of the nail matrix, creating an environment that avoids nail regrowth.