Clinicopathological and targeted exome gene features of a patient with metastatic acinic cell carcinoma of the parotid gland harboring an ARID2 nonsense mutation and CDKN2A/B deletion

We describe the presentation, treatment, clinical outcome, and targeted genome analysis of a metastatic salivary acinic cell carcinoma (AciCC). A 71-year-old male presented with a 3 cm right tail of a parotid lesion, first detected as a nodule by the patient seven months earlier. He had a right total parotidectomy with cranial nerve VII resection, right facial nerve resection and grafting, resection of the right conchal cartilage, and right modified radical neck dissection. The primary tumor revealed AciCC with two distinct areas: a well-differentiated component with glandular architecture and a dedifferentiated component with infiltrative growth pattern associated with prominent stromal response, necrosis, perineural invasion, and cellular pleomorphism. Tumor staging was pT4 N0 MX. Immunohistochemistry staining showed pankeratin (+), CD56 (−), and a Ki67 proliferation index of 15%. Upon microscopic inspection, 49 local lymph nodes resected during parotidectomy were negative for cancer cells. Targeted sequencing of the primary tumor revealed deletions of CDKN2A and CDKN2B, a nonsense mutation in ARID2, and single missense mutations of unknown significance in nine other genes. Despite postoperative localized radiation treatment, follow-up whole body PET/CT scan showed lung, soft tissue, bone, and liver metastases. The patient expired 9 months after resection of the primary tumor

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Long-term follow-up of a Patient with Malignant Transformation of Inverted Papilloma into Sinonasal Undifferentiated Carcinoma

Introduction Inverted papillomas (IP) are benign sinonasal neoplasms, which account for 0.5–4% of all nasal tumors. IPs have been known to transform into squamous cell carcinoma in 5–15% of cases. Rarely, transformations to other malignancies have been reported. Here we report a unique case of malignant transformation of an IP into sinonasal undifferentiated carcinoma (SNUC). Methods A case report with a literature review; institutional review board exempted. The clinical presentation, radiographic features, surgical intervention, histopathologic analysis, treatment, and outcome of the case were examined. Results A 62-year-old man presented with a 3-month history of nasal airway obstruction, rhinorrhea, and postnasal drip refractory to medical therapy. He had a long history of exposure to fumes, chemicals, dusts, and solvents as a professional painter as well as a 45 pack-year history of smoking and alcohol abuse. The patient was ultimately found to have a left ethmoidal IP with a focus of malignant transformation into SNUC. Endoscopic resection was performed, followed by concurrent chemoradiation and adjuvant chemotherapy. After surgery, he had no evidence of recurrent disease after 9 years of follow-up. Conclusions IP is known to transform into squamous cell carcinoma. Here we report a rare case of malignant transformation into SNUC, a much more uncommon and aggressive lesion. Although traditionally associated with a poorer prognosis, the positive outcome for SNUC observed in this patient may potentially be attributed to early detection and timely therapeutic intervention