The diagnosis of double adenomas of the pituitary can be very complex and is usually suspected on histological assessment of a specimen and confirmed by immunohistochemical and ultrastructural studies. The most commonly applied technique is currently immunohistochemical staining to localize the six pituitary hormones. Application of this technique may fail to identify double adenomas when hormone immunoreactivity is weak or absent in one or both cell populations. We examined specimens from eight patients diagnosed with double adenomas over a 15-yr period. We tested the ability to detect the difference in the two adenomas in each case using three immunostains for the pituitary transcription factors Pit-1, T-pit, and SF-1. We conclude that immunohistochemical localization of the transcription factors Pit-1, T-pit, and SF-1 accurately detects and classifies the distinct cytodifferentiation of double adenomas of the pituitary.

This study characterized cases with a negative high-risk Hybrid Capture 2 (HRHC2; Digene, Gaithersburg, MD) test result with concurrent or follow-up biopsy-confirmed high-grade cervical intraepithelial neoplasia (CIN 2/3). From 2,306 HRHC2 tests, 10 negative results were identified with CIN 2/3 (false-negative rate, 4.5%). The majority of the patients had abnormal colposcopic findings and high-grade squamous intraepithelial lesion (HSIL) shown by concurrent cytologic examination, although with few abnormal cells. No trend was evident in the location of the dysplastic epithelium or overall lesion size. In 4 tests, the relative light units over cutoff was more than 0.4 but less than 1.0, suggesting that low quantities of human papillomavirus (HPV) DNA were present in the sample. The negative predictive value for HRHC2 testing may be compromised when the copy number of the HPV DNA is low, and a negative HRHC2 test result may be falsely negative in patients with abnormal colposcopic findings or concurrent cytologic findings showing HSIL.

Choroid plexus papilloma (CPP) is a rare benign tumor of the central nervous system that is usually confined to the cerebral ventricles. According to the World Health Organization, CPP corresponds to a grade I atypical CPP (a-CPP); however, it can become more aggressive and reach grade II, which can rarely undergo malignant transformation into a choroid plexus carcinoma (grade III). To the best of our knowledge, identification of these tumors mutations by next generation DNA sequencing (NGS) has not been yet reported. In the present study, NGS analysis of an a-CPP case was performed. Data were analyzed using Advaita Bioinformatics i-VariantGuide and Ion Reporter 5.6 programs. The results from NGS identified 12 novel missense mutations in the following genes: NOTCH1, ATM, STK36, MAGI1, DST, RECQL4, NUMA1, THBS1, MYH11, MALT1, SMARCA4 and CDH20. The PolyPhen score of six variants viz., DST, RECQL4, NUMA1, THBS1, MYHI1 and SMARCA4 were high, which suggested these variants represents pathogenic variants. Two novel insertions that caused frameshift were also found. Furthermore, two novel nonsense mutations and 14 novel intronic variants were identified in this tumor. The novel missense mutation detected in ATM gene was situated in c.5808A>T; p. (Leu1936Phe) in exon 39, and a known ATM mutation was in c.5948A>G; p. (Asn1983Ser). These novel mutations had not been reported in previous database. Subsequently, the quality statistics of these variants, including allele coverage, allele ratio, P-value, Phred quality score, sequencing coverage, PolyPhen score and alleles frequency was performed. For all variants, P-value was highly significant and the Phred quality score was high. In addition, the results from sequencing coverage demonstrated that 97.02% reads were on target and that 97.88% amplicons had at least 500 reads. These findings may serve at determining new strategies to distinguish the types of choroid plexus tumor, and at developing novel targeted therapies. Development of NGS technologies in the Kingdom of Saudi Arabia may be used in molecular pathology laboratories.