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

Adrenocortical Carcinoma: Updates of Clinical and Pathological Features after Renewed World Health Organisation Classification and Pathology Staging

Adrenocortical carcinoma (ACC) is a heterogenous group of diseases with different clinical behaviour between adult and paediatric patients. In addition, three histological variants, oncocytic, myxoid and sarcomatoid are noted on the recent World Health Organisation (WHO) classification of ACC. A review of recent literature showed that the different types of ACC have distinctive demographic data, clinical presentation, pathology, biological behaviour, genomic and patients’ prognosis. In addition, recent updates of pathology staging for ACC allow refinement of prognostic grouping for planning treatment of the patients with ACC. These advances in genomic, pathology and staging have driven the development of standardisation of pathology reporting. International standardisation of pathological reporting of adrenocortical carcinoma and adaption to local pathology communities provide universal platforms for clinicians and researchers involved in the management of patients with ACC. To conclude, all these advances in the field of pathology will improve development of management strategies including improvement of clinical care, development of prognostic markers and testing of novel therapeutic approaches for patients with adrenocortical carcinoma

Pancreatic neuroendocrine neoplasms: Clinicopathological features and pathological staging

. The nomenclature and classification of pancreatic neuroendocrine neoplasms has evolved in the last 15 years based on the advances in knowledge of the genomics, clinical behaviour and response to therapies. The current 2019 World Health Organization classification of pancreatic neuroendocrine neoplasms categorises them into three groups; pancreatic neuroendocrine tumours (PanNETs) (grade 1 grade 2, grade 3), pancreatic neuroendocrine carcinomas and mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) based on the mitotic rate, Ki-67 index, morphological differentiation and/or co-existing tissue subtype. PanNETs are also classified into non-functional NET, insulinoma, gastrinoma, VIPoma, glucagonoma, somatostatinoma, ACTH-producing NET and serotonin producing NET based on hormone production and clinical manifestations. A portion of the cases were associated with genetic syndromes such as multiple neuroendocrine neoplasia 1 (MEN 1), neurofibromatosis and Von Hippel-Lindau syndrome. In view of the distinctive pathology and clinical behaviour of PanNENs, the current 8th AJCC/UICC staging system has separated prognostic staging grouping for PanNETs from the pancreatic neuroendocrine carcinomas or MiNENs. Pancreatic neuroendocrine carcinomas and MiNENs are staged according to the prognostic stage grouping for exocrine pancreatic carcinoma. The new stage grouping of PanNETs was validated to have survival curves separated between different prognostic groups. This refined histological and staging would lead to appropriate selections of treatment strategies for the patients with pancreatic neuroendocrine neoplasm

Anaplastic thyroid carcinoma: Updates on WHO classification, clinicopathological features and staging

Anaplastic thyroid carcinoma is an uncommon carcinoma representing 1 to 4% of all thyroid cancers. The carcinoma is most common in females of the eight decades. It is a locally advanced cancer with frequent infiltration of surrounding organs, blood vessels and skin of neck. Paraneoplastic manifestations could occur. Approximately half of the patients with anaplastic thyroid carcinoma had distant metastasis with lung and brain as the most frequent sites of metastasis. The median survival of patients with anaplastic thyroid carcinoma reported was from 1 to 6 months. The terminology of the cancer in World Health Organization is "anaplastic thyroid carcinoma" rather than "undifferentiated thyroid carcinoma". In the latest American Joint Committee on Cancer (AJCC) TNM staging system for anaplastic thyroid carcinoma, there are updates on T and N categories. To conclude, updated knowledge of clinicopathological features, classification, pathological staging will improve our understanding of the cancer and will help in the management of the patients with this aggressive cancer

Primary squamous cell carcinoma of the rectum in a patient on immunosuppressive therapy

Primary squamous cell carcinoma of the rectum is a rare\ud tumour.1–11 The diagnosis of squamous cell carcinoma rests\ud on the exclusion of metastases from other organs, proximal\ud extension of carcinoma arising from the anal canal and\ud squamous-lined fistulous tracts. Here we report an uncommon\ud presentation of rectal squamous cell carcinoma in a\ud woman on long-term immunosuppressive therapy

Pathology and molecular biology of malignant thyroid tumours

published_or_final_versiontocabstractMedicineMasterDoctor of Medicin

Clinicopathological and Molecular Features of Secondary Cancer (Metastasis) to the Thyroid and Advances in Management

Secondary tumours to the thyroid gland are uncommon and often incidentally discovered on imaging. Symptomatic patients often present with a neck mass. Collision tumours of secondary tumours and primary thyroid neoplasms do occur. Ultrasound-guided fine-needle aspiration, core-needle biopsy, and surgical resection with histological and immunohistochemical analysis are employed to confirm diagnosis as well as for applying molecular studies to identify candidates for targeted therapy. Biopsy at the metastatic site can identify mutations (such as EGFR, K-Ras, VHL) and translocations (such as EML4-ALK fusion) important in planning target therapies. Patients with advanced-stage primary cancers, widespread dissemination, or unknown primary origin often have a poor prognosis. Those with isolated metastasis to the thyroid have better survival outcomes and are more likely to undergo thyroid resection. Systemic therapies, such as chemotherapy and hormonal therapy, are often used as adjuvant treatment post-operatively or in patients with disseminated disease. New targeted therapies, such as tyrosine kinase inhibitors and immune checkpoint inhibitors, have shown success in reported cases. A tailored treatment plan based on primary tumour features, overall cancer burden, and co-morbidities is imperative. To conclude, secondary cancer to the thyroid is uncommon, and awareness of the updates on diagnosis and management is needed