TBX3 Promotes Cervical Cancer Proliferation and Migration via HPV E6 and E7 Signaling.

Cervical cancer is a leading cause of cancer-related deaths in women globally and 99% of cases are caused by persistent infection with high-risk strains of the human papillomavirus (HPV). The HPV oncoproteins E6 and E7 establish the cancer phenotype by cooperating with host proteins and identifying them may have important therapeutic benefits. T-box transcription factor 3 (TBX3) is a critical developmental regulator, and when it is overexpressed postnatally, it contributes to several cancers, but little is known about its expression and role in cervical cancer. The current study shows that TBX3 is upregulated in cervical cancer cell lines as well as precancerous and cervical cancer patient tissue and is associated with larger and more invasive tumors. Knockdown and overexpression cell culture models show that TBX3 promotes HPV-positive cell proliferation, migration, and spheroid growth; however, TBX3 inhibits these processes in HPV-negative cells. Importantly, we show that the tumor promoting activity of TBX3 in cervical cancer is dependent on E6/E7. IMPLICATIONS: In summary, our study highlights the importance of TBX3 as a cooperating partner of E6/E7 in HPV-positive cervical cancer and identifies TBX3 as a potential therapeutic target to treat this neoplasm.

Mucoepidermoid carcinoma ex pleomorphic adenoma: A rare diagnostically challenging entity.

Mucoepidermoid carcinoma (MEC) arising in pleomorphic adenoma (PA) is an extremely rare entity. Involvement of minor salivary glands by this entity has only being described twice previously. We report on a diagnostically challenging case in an 18 year old male with a large mass in the junction of the hard and soft palates that has been present for 12 months. Both cytology and incisional biopsy were inconclusive and indicated benign mixed tumour. Upon excision of the tumour with a 5 mm clear margin, histology demonstrated PA that has been replaced by small nests and cribriform islands of high-grade MEC with 13 mm of invasion beyond the original PA capsule. The tumour was composed of mostly intermediate-type cells with up to 7 mitoses per 10 high power fields. The tumour cells were positive for cytokeratin (CAM 5.2) and S100. Due to the high-grade nature and focal positive posterior margin of the resected specimen, adjuvant radiotherapy was administered. In conclusion, this case highlights the need to consider rare entities such as mucoepidermoid carcinoma ex pleomorphic adenoma in atypical cytological and histological findings. Moreover, it underlines the need to manage lesions with unconfirmed histological diagnosis with wide excision margins to avoid having involved margins post resection.

The histological significance of atypical glandular cells on cervical cytology: Experience at Groote Schuur Hospital, Cape Town, South Africa.

BACKGROUND: Atypical glandular cells (AGC) identified on Pap tests may be markers for potentially significant pathology. OBJECTIVES: Primarily, to correlate AGC findings at Groote Schuur Hospital (GSH, Cape Town, South Africa) with subsequent histological investigations and attempt to identify predictors of pathology relevant to the clinical management of women with a cytological diagnosis of AGC. Secondly, to compare the GSH data with data from similar international studies. METHODS: Records of AGC Pap tests were retrieved from the laboratory database in the anatomical pathology laboratory at GSH and clinically relevant information was summarised based on the available information. Standard descriptive statistics were used to summarise the study data, and Fisher's exact test was used to compare categorical outcomes, where possible. RESULTS: Of the 237 women with a cytological diagnosis of AGC and who had subsequent histological diagnoses, 120 (50.6%) had significant pathology (cervical intraepithelial neoplasia (CIN) 2 or worse). Significant cervical pathology was most common in women aged <50 years, while significant endometrial pathology predominated in women aged ≥50 years. The results of the GSH study were largely consistent with international findings, but the risk of malignancy was six times higher in the GSH population than in a comparable international group. CONCLUSION: AGC identified on Pap tests may be markers for potentially significant pathology. Human papillomavirus DNA testing is recommended for younger women diagnosed with AGC to reduce invasive investigations and minimise expenses in a resource-poor setting.

Rapidly progressive post-transplant lymphoproliferative disease following withdrawal of sirolimus.

Sirolimus, a potent inhibitor of B- and T-cell activation. is a commonly used immunosuppressant after renal transplantation. Withdrawal of sirolimus from the immunosuppression regimen may reduce B-cell surveillance. We present a case of rapidly progressive central nervous system (CNS) polymorphic Epstein-Barr virus (EBV)-related post-transplant lymphoproliferative disorder following the withdrawal of sirolimus.

Tetraphocomelia with the Waardenburg syndrome and multiple malformations.

A male infant delivered spontaneously at the 29th week of pregnancy had gross tetraphocomelia and features of the Waardenburg syndrome. There were no relevant factors in the pregnancy nor family history. It is possible that microdeletions or contiguous gene defects are involved in the pathogenesis of these malformations.