PD-L1-positive circulating endothelial progenitor cells associated with immune response to PD-1 blockade in patients with head and neck squamous cell carcinoma.

A number of the inhibitors against programmed death protein 1 (PD-1) have been approved to treat recurrent or metastatic squamous cell carcinoma of head and neck (HNSCC). The interaction between PD-1 and its ligand (PD-L1) serves as an immune checkpoint that governs cytotoxic immune effectors against tumors. Numerous clinical trials of PD-1/PD-L1 inhibitors have so far been discordant about having sufficient PD-L1 expression in the tumor as a prerequisite for a successful anti-PD-1 treatment. On the other hand, vascular endothelial cells modulate immune activities through PD-L1 expression, and thus it is possible that the expressions of circulating endothelial cells (CECs) and circulating endothelial progenitor cells (CPCs) could affect antitumor immunity as well as neoangiogenesis. Here we investigated the potential involvement of PD-L1+ CECs and PD-L1+ CPCs in PD-1 blockade treatments for HNSCC patients. We measured CD8+ T cells, CECs, and CPCs in the peripheral blood of the HNSCC patients treated by anti-PD-1 therapies. We found that their PD-L1+ CPC expression before anti-PD1 therapies was strongly correlated with treatment responses and overall survival. Moreover, if the first infusion of PD-1 inhibitors reduced ≥ 50% PD-L1+ CPCs, a significantly better outcome could be predicted. In these patients as well as in an animal model of oral cancer, Pd-l1+ CPC expression was associated with limited CD8+ T-cell infiltration into the tumors, and anti-PD-1 treatments also targeted Pd-l1+ CPCs and increased CD8+ T-cell infiltration. Our results highlight PD-L1+ CPC as a potential regulator in the anti-PD-1 treatments for HNSCC.

Acromegaly with initial negative oral glucose tolerance test: a case report.

BACKGROUND: Acromegaly can be diagnosed by a growth hormone value ≥ 1 µg/L following an oral glucose tolerance test. However, normal growth hormone suppression following oral glucose tolerance test may not exclude acromegaly. CASE PRESENTATION: We present a case of a 55-year-old Chinese man with pituitary macroadenoma incidentally noted after a traffic accident. He reported feet enlargement in the past few years. At the beginning, elevated insulin-like growth factor-1 was noted with growth hormone value < 1 µg/L after oral glucose tolerance test. Fracture-related high insulin-like growth factor-1 was suspected. Insulin-like growth factor-1 decreased gradually but was still above the upper limit of normal . However, he suffered from dizziness 1 year later and insulin-like growth factor-1 increased again. Besides, secondary hypocortisolism developed. The size of the pituitary macroadenoma was stationary. Follow-up oral glucose tolerance test showed a growth hormone value > 1 µg/L. Endoscopic endonasal approach to the remove pituitary macroadenoma was performed subsequently. After the resection of the pituitary macroadenoma, pathology showed positive staining of growth hormone and prolactin. Insulin-like growth factor-1 normalized as well. CONCLUSIONS: Suppressed growth hormone after oral glucose tolerance test cannot exclude acromegaly, and some patients may have only mild or no clinical presentation of acromegaly. Patients with pituitary microadenoma or macroadenoma and elevated insulin-like growth factor-1 should be closely monitored for signs/symptoms of acromegaly and hypopituitarism.

A Clinicopathological Analysis of Asian Patients with Adrenocortical Carcinoma: A Single-Center Experience.

BACKGROUND: There is limited information regarding the immunohistochemistry stain and its prognostic role in adrenocortical carcinoma (ACC), and few studies focus on Asian patients. Our study aims to identify the correlation between immunohistochemistry staining and the prognosis of ACC in Asian patients. METHODS: We searched the database of a single center in Taiwan for cases with a pathological diagnosis of ACC in the past 25 years. We collected patient data on age, sex, initial presentation, staging, metastatic site, and survival duration. Immunohistochemical studies using antibodies to CDK4, ATRX, beta-catenin, Ki-67, SSTR2, and p53 were performed. Survival analysis was performed using the log-rank test, the Cox proportional hazards model and bootstrapping with 5000 samplings. RESULTS: Fourteen patients were identified, and the median age was 49.5 (range 1-70) years. There were eight male and six female patients. Four patients presented with Cushing's syndrome, and half were diagnosed with stage IV ACC at presentation. Only three patients survived (21%). The median survival time was 15.5 (range 0.67-244) months. SSTR2 expression score > 50 (log-rank test: p = 0.009) and Ki-67 > 50% (log-rank test: p = 0.017) were associated with mortality. However, after adjusting for stage, the bootstrapping analysis demonstrated that Ki-67 [B 2.04, p = 0.004], Beta-catenin [B 2.19, p = 0.009], ATRX [B 1.48, p = 0.026], P53 [B 1.58, p = 0.027], SSTR2 [B 1.58, p = 0.015] and SSTR2 expression score [B 0.03, p < 0.001] were all significantly associated with mortality. CONCLUSIONS: After adjusting for stage, Ki-67 > 50%, Beta-catenin, ATRX, P53, SSTR2 and SSTR2 expression score > 50 were associated with mortality in Asian patients with ACC.

Double water-clear cell parathyroid adenoma: a case report and literature review.

Water-clear cell parathyroid adenoma is an uncommon cause of primary hyperparathyroidism. Herein, we report an interesting case of a 56-year-old man who presented with weight loss, bone pain, fatigue, and a palpable right neck mass. Laboratory tests indicated hypercalcemia, elevated parathyroid hormone (PTH) levels, and normal thyroid function. Further examinations detected osteoporosis and kidney stones. The ultrasound of neck revealed bilateral extrathyroidal tumors, which were sestamibi-avid. The patient underwent resection of the large right inferior and left inferior parathyroid tumors. Histopathology revealed a double water-clear cell parathyroid adenoma. His serum calcium and PTH levels normalized after surgery. The literature review identified 37 cases of water-clear cell parathyroid adenoma between 1985 and 2021. The median age at diagnosis was 56 years. Classic complications were common, including nephrolithiasis in nine and skeletal presentations in 10 patients. Before surgery, the median calcium and PTH levels were 12.0 mg/dL and 290 pg/mL, respectively. Overall, 89% were localized on ultrasonography, and 60% were positive on scintigraphy. Four patients had double adenomas. The median maximum diameter was 3.8 cm, and the median weight of the resected adenoma was 5.27 g. In summary, water-clear cell parathyroid adenoma has certain unique features. These include larger tumor size, relatively indolent biochemical profile, high prevalence of complications and nonspecific symptoms, an isoechoic appearance on ultrasonography, and reduced scintigraphic sensitivity.

Case Report: Ectopic Adrenocortical Carcinoma in the Ovary.

Adrenocortical carcinoma (ACC) is a rare malignancy with an incidence of 0.7-2.0 cases/million habitants/year. ACCs are rare and usually endocrinologically functional. We present the case of a 59-year-old woman who experienced abdominal fullness for 6 months and increased abdominal circumference. A large pelvic tumor was observed. She underwent cytoreductive surgery and the pathological test results revealed local tumor necrosis and prominent lympho-vascular invasion. Neuroendocrine carcinoma was the first impression, but positivity for synaptophysin, alpha-inhibin, transcription factor enhancer 3 (TFE-3), calretinin (focal), and CD56 (focal) and high Ki-67-labeling proliferating index (>80%) confirmed the diagnosis of ectopic ACC. Ectopic primary aldosteronism could not be excluded. However, we did not perform saline infusion test or captopril test due to poor performance status. When pathological test reports reveal neuroendocrine features not typically found in the organ being examined, IHC staining should be performed to rule out ectopic ACC. Whether the ectopic ACC is functional or not requires complete survey.

Adrenal Tumor Mimicking Non-Classic Congenital Adrenal Hyperplasia.

Elevated 17-hydroxyprogesterone may be caused by congenital adrenal hyperplasia, ovarian or adrenal tumors. A positive cosyntropin stimulation test result for 17-hydroxyprogesterone may be found in functional or non-functional tumors and be related to tumor size. Here, we present a case of a 36-year-old woman with a 4-year history of infertility. Laboratory test results revealed elevated progesterone and 17-hydroxyprogesterone, with normal luteinizing hormone, follicle-stimulating hormone, estrogen, testosterone, and anti-Mullerian hormone levels. The 250-µg cosyntropin stimulation test revealed a 17-hydroxyprogesterone level of 11.3 ng/ml (34.3 nmol/L) and 31.8 ng/ml (96.2 nmol/L) at 0 and 60 min, respectively. Non-classic congenital adrenal hyperplasia was diagnosed initially; however, genetic testing revealed no 21-hydroxylase deficiency. She received dexamethasone but progesterone and 17-hydroxyprogesterone levels remained high. Abdominal computed tomography found a 4.5 × 4.8-cm left adrenal tumor. Subsequent pathological report was compatible with an adrenal cortical adenoma. Progesterone and 17-hydroxyprogesterone levels returned to the normal range postoperatively and the 250-µg cosyntropin stimulation test of 17-hydroxyprogesterone showed a normal response. When biochemically diagnosed NCCAH demonstrate no typical features and show poor response to steroid, the patient should undergo gene mutation analysis and receive adrenal or ovarian imaging. For women suffering from infertility, adrenalectomy of 17-OHP secreting adrenal tumor may improve fertility outcome.

Overexpression of Histone H3 Lysine 27 Trimethylation Is Associated with Aggressiveness and Dedifferentiation of Thyroid Cancer.

A variety of epigenetic dysregulations are observed in thyroid malignancies. EZH2, the catalytic subunit of polycomb repressive complex 2, is upregulated in advanced thyroid cancers. EZH2 can catalyze trimethylation of histone H3 at lysine 27 (H3K27me3) and contribute to transcriptional silencing of target genes. Here, we investigated the immunohistochemical expression of H3K27me3 in neoplastic and normal thyroid tissues. Normal thyroid epithelial cells typically exhibited nuclear staining of moderate intensity. A similar expression pattern was observed in nodular goiters and follicular adenomas. By contrast, strong H3K27me3 expression was evident in 80% (8/10) lymphocytic thyroiditis, 63% (80/127) papillary thyroid cancer, 41% (7/17) follicular thyroid cancer, and 73% (8/11) poorly differentiated and anaplastic thyroid cancer. In differentiated thyroid cancer, strong H3K27me3 expression was associated with extrathyroidal extension (p < 0.001), lymphovascular invasion (p = 0.029), lymph node metastasis (p = 0.006), and higher risk of recurrence (p = 0.003). Our results indicate that H3K27me3 overexpression may be implicated in aggressiveness and dedifferentiation of thyroid cancer. In addition to prognostication, the predictive value of H3K27me3 expression deserves further investigation given the recent development of epigenetic targeting agents.

Compare Fuhrman Nuclear and Chromophobe Tumor Grade on Chromophobe RCC.

BACKGROUND: Chromophobe renal cell carcinoma (chRCC) has a favorable prognosis. Due to irregular nuclei and nuclear pleomorphism, chRCC has a high Fuhrman nuclear grade (FNG). The chromophobe tumor grade (CTG) is a novel three-tier grading system that has been reported to be a better prognosticator than the traditional FNG. We compared the two nuclear grading systems in terms of patients' clinical outcomes. PATIENTS AND METHOD: We performed this retrospective chart review of all patients with chRCC from 2000 to 2017. All pathologic features and CTG and FNG results were re-evaluated. RESULT: Eighteen patients' records were reviewed with a mean follow-up of 70.6 months. The nuclear grading distribution was as follows: FNG 2, 56%; FNG 3, 39%; FNG 4, 5%; CTG 1, 78%; CTG 2, 17%; and CTG 3, 6%. Only one patient died. This patient had adrenal invasion, lung metastasis, sarcomatoid change and tumor necrosis, and the tumor was graded as FNG 4 and CTG 3. Overall survival was associated with both FNG and CTG. CONCLUSION: Chromophobe RCC was associated with a low rate of cancer-specific death and sarcomatoid differentiation. Both FNG and CTG were associated with overall survival.

Erratum: A glomus tumor of the lung of uncertain malignant potential: a case report.

[This corrects the article on p. 6039 in vol. 11, PMID: 31949693.].

A glomus tumor of the lung of uncertain malignant potential: a case report.

Glomus tumors are relatively rare tumors, especially those of bronchopulmonary origin. Fewer than 50 cases of glomus tumors of the lung have been reported in the English medical literature, and the majority of them were clinically benign. We report on a 15-year-old boy with a nodule in the left lung bronchus. The microscopic examination revealed a glomus tumor with an uncertain malignant potential.