2018年 · 第98卷第09期

The 2017 edition of the World Health Organization (WHO) pituitary tumor classification has been released recently^[1]Understanding the evolution of pituitary tumor classification will not only help clinicians to make a clear diagnosis and treatment of pituitary tumors, but also help them to conduct more in-depth translational research and further targeted therapy^[2]。 With the deepening of genomics, transcriptomics and metabolomics, people's understanding of pituitary tumors has been further deepened. The significance and implications of the 2017 version of WHO pituitary tumor classification are now reviewed as follows.

The 4th edition of the 2017 World Health Organization (WHO) new classification of endocrine organ tumors (hereinafter referred to as the new classification) has been published^[1]The changes from histopathology to molecular genetics of pituitary tumors have updated people's understanding, especially in the future clinical and scientific research work, it is necessary to combine a new classification system to standardize the diagnosis and treatment of pituitary tumors. Combined with the new classification, this article focuses on the classification of anterior pituitary tumors, and talks about the enlightenment and confusion brought to us by the new classification.

The release of the 2017 edition of the World Health Organization (WHO) Classification of Endocrine Tumors (hereinafter referred to as the new edition) has attracted wide attention from scholars from all walks of life^[1]。 The new version of the Endocrine Tumor Tissue Classification provides a subversive new definition of the classification of neuroendocrine tumors derived from the anterior pituitary gland.

The latest edition of the World Health Organization (WHO) Classification of Endocrine System Tumors (2017 Edition) was recently released. Some major changes have taken place in the classification of pituitary neuroendocrine tumors in the new edition. The main changes in the classification of pituitary endocrine tumors in the new edition focus on the following aspects^[1,2]: (1) the term "atypical pituitary adenoma" was removed; (2) introduction of a new tumor entity, "pituitary blastoma"; (3) The naming of pituitary adenoma has changed: it is no longer named after the type of secreted hormone, but after the differentiation lineage of tumor cells that make up the adenoma. For example, the naming of growth hormone adenoma is abolished and growth hormone cell adenoma is used to name; (4) Redefining some old solid tumors, such as zero cell adenomas, according to transcription factor expression; (5) highlighting five "high-risk pituitary adenomas", including sparse granular growth hormone cell adenomas, multi-hormone pituitary-specific Pou-homologous domain transcription factor (PIT-1) positive adenomas (previously known as quiescent third subtype adenomas), quiescent corticotropin cell adenomas, Crooke cell adenomas, and male prolactin cell adenomas; (6) The relationship between transcription factors and pituitary adenomas is pointed out, so that the classification of pituitary adenomas no longer relies on ultrastructural analysis; (7) It is strongly recommended to comprehensively assess whether adenomas are aggressive by evaluating clinical imaging parameters such as tumor proliferative potential (counting mitotic images and Ki-67 index) and invasion of surrounding tissues.

The 4th edition of the World Health Organization (WHO) Classification of Endocrine Organ Tumors was released in 2017^[1]In which a new description of the classification of pituitary tumors is given, seeTable 1Compared with the 3rd edition of the WHO classification in 2004^[2]。

Example 1: Child (1-IV-17), female, 3 years old. He was admitted to the General Hospital of the People's Liberation Army in May 2011 because he was "unable to walk for three years since childhood". The child has difficulty walking since childhood without obvious incentives, abnormal standing posture, touching the ground with both toes, unable to walk alone, and easy to fall. The above symptoms include light morning and heavy evening phenomenon, stiffness of both lower limbs in the afternoon, and obvious at night. Symptoms worsened slowly, there was no abnormality in both upper limbs, and speaking and eating were normal. The local hospital treated it according to "cerebral palsy", but the condition did not improve significantly. Physical examination: The muscle tone of the limbs was gearlike increased, obvious in both lower limbs, active tendon reflex of the limbs, mild inversion of both feet, and bilateral pathological signs (-). Ophthalmic examination did not show K-F rings. Liver and kidney function, serum ceruloplasmin (CP), serum copper and 24-h urine copper were all normal. Brain MRI and neuroelectrophysiological examination were normal. The initial diagnosis was dopa-responsive dystonia (DRD), and the patient was given dopaserazide (trade name Medopa) 62.5 mg, 3 times/d, and functional exercise and equipment rehabilitation therapy were used to help correct foot varus. The patient could walk on his own, and then continued to take Medopa orally at the original dose. After taking the medicine for 1 or 2 years, the patient was stable at outpatient follow-up. After taking Medopa 62.5 mg for a long time, 3 times/d for maintenance therapy, the patient could walk on his own.

The 56-year-old female was admitted to the Department of Gastroenterology, Affiliated Hospital of North China University of Science and Technology on May 6, 2017 due to intermittent epigastric pain for more than 10 years and recurrence with melena for 3 days. More than 10 years ago, the patient had intermittent upper abdominal pain without obvious trigger, which was obvious when hungry and could be relieved after eating. The abdominal pain recurred, intermittently accompanied by melena, and no formal diagnosis and treatment was given. Three days before admission, abdominal pain recurred, accompanied by melena, black shaped stools were defecated once a day, with a amount of about 150 g, and palpitations occurred after defecation. Physical examination at admission: anemic appearance, flat abdomen, no gastrointestinal type, soft abdomen, mild tenderness in the upper abdomen, no rebound pain and muscle tension in the whole abdomen, and normal intestinal sounds. Blood routine after admission, red blood cell count 1.92×10¹²/L, hemoglobin 61 g/L. Stool routine showed positive occult blood. Gastroscopy showed a bulging lesion on the anterior wall of the lower part of the stomach body, with clear boundaries, about 4.0 cm ×4.0 cm, covered with white coating, and the biopsy was tough (Figure 1)。 Microscopic diagnosis: (1) The nature of gastric body bulge type lesion to be determined-gastric stromal tumor? (2) gastric fundus polyps; (3) Chronic non-atrophic gastritis with erosion. Pathological examination of gastroscopic biopsy showed that the gastric fundus polyps were mild chronic active mucosal inflammation, and the gastric body mass submitted for examination was inflammatory necrotic tissue. After the patient's anemia was improved, surgical exploration was performed. During the operation, the anterior wall of the great curvature of the stomach was longitudinally incised. A spherical mass, about 4 cm in diameter, intracavitary, smooth, medium texture, good mobility, no gastric mucosal layer covered, surface ulcer formation was seen, and the base was close to the gastric angle. The mass was completely removed and the pathology was submitted for examination. Postoperative pathological report (Figure 2): Gastric angle mass dendritic fibromyxoid lipoma (DFML), the tumor size is 3.5 cm ×2.7 cm ×2 cm, the main tumor body is located in the submucosal layer, and the mucosal layer is involved to form superficial ulcer. Immunohistochemical results: STAT6 (cytoplasmic +), CD34 (partial +), Bcl-2 (+), CD99 (weak +), ALK (-), DOG-1 (-), CD117 (-), β-catenin (-), HMB45 (-), actin (smooth muscle +), S-100 (-). After operation, he was given routine fasting, acid suppression, anti-inflammatory, fluid rehydration and other treatments. He recovered well after operation, with no progression of anemia, and routine occult blood in feces turned negative. He has recovered and been discharged.

Pituitary tumors are one of the most common intracranial tumors in clinic, with a population incidence of about 9 in 10,000. According to the level of hormone secretion, pituitary adenomas are classified into functional pituitary adenomas and non-functional adenomas. Functional pituitary tumors are mainly divided into prolactin (PRL), growth hormone (GH), adrenocorticotropic hormone (ACTH) and thyroid stimulating hormone (TSH)^[1]。 The mechanism of pituitary tumors is still unclear, but some studies have shown that it is formed by the activation of oncogenes, inactivation of tumor suppressor genes and downregulation of microRNA. There is also the involvement of certain cytokines, such as interleukin-6 (IL-6) and the like. It is worth pointing out that IL-6 is involved in the progression of tumor cell senescence and may act as a mechanism for pituitary tumors to maintain benign growth^[2,3]。 The clinical manifestations of pituitary tumors are abnormal hormone secretion, neurological symptoms caused by tumor compression of peripituitary tissues, pituitary stroke, and other anterior hypopituitary function. At present, the treatment methods of pituitary adenoma mainly include surgery, radiotherapy and drug therapy, among which dopamine receptor agonist treatment is the first choice for patients with PRL tumor. Recently, immunotherapy has developed rapidly in tumor treatment, and has achieved remarkable clinical results. Among them, blocking the immunosuppressive target (PD-1) on the surface of T cells to activate the immune function of T cells has been approved by the FDA as a treatment for melanoma, lung cancer and kidney cancer. At the same time, the research of immunotherapy in the treatment of pituitary tumors continues to make progress, and it is expected to become an important treatment after surgery, radiotherapy and drug therapy^[4]。

With the aging of the population, the incidence of osteoporosis is increasing year by year, and it has gradually become one of the global health problems to be solved urgently^[1,2]。 China is a country with a high incidence of osteoporosis. According to the national epidemiological survey from 2003 to 2006, the prevalence rate of osteoporosis among people over 50 years old in China is about 14.4% in men and 20.7% in women, which brings a huge economic burden to the families and society of patients^[2]。 Primary osteoporosis is mainly divided into postmenopausal osteoporosis (type I) and senile osteoporosis (type II). Pathologically, the main manifestations are bone mass reduction per unit volume, bone microstructure degradation and bone strength reduction. The former is mainly associated with decreased estrogen levels and increased osteoclast activity, while the latter is mainly age-related physiological degeneration^[2]。 Fractures are the most common complication of osteoporosis, among which non-traumatic fractures of the hip, femoral neck and spine are the most common and are the main causes of paralysis and death in patients^[2,3]。

Cholangiocarcinoma (CCA) is a malignant tumor originating from bile duct epithelial cells, which can occur in any part of the bile duct tree. According to the anatomical location, it can be divided into intrahepatic Cholangiocarcinoma (iCCA), hilar Cholangiocarcinoma (pCCA), and distal Cholangiocarcinoma (dCCA)^[1]。 Epidemiological data show that the incidence and prevalence of cholangiocarcinoma are increasing worldwide, and the mortality rate is increasing accordingly^[2]。 Although the tumor grows slowly and metastasizes late, due to the special anatomical site of cholangiocarcinoma, coupled with its characteristics of infiltration and spread along blood vessels and nerve sheaths, it is usually at an advanced stage when discovered, and radical surgery is often difficult to achieve the expected efficacy. Most patients with unresectable tumors die of liver failure or biliary obstruction within one year^[1,3]Cholangiocarcinoma is seriously threatening the lives of patients. At present, it is believed that the occurrence and development of cholangiocarcinoma is a multi-factor and multi-step pathological process, which involves the activation of oncogene, inactivation of tumor suppressor gene, tumor metastasis, apoptosis and abnormal cell cycle regulation, tumor genetics and epigenetic changes, etc^[4]。 Wnt signaling pathway is a highly conserved signaling pathway in animals and plants, which regulates and controls many life processes, including growth, development, disease, aging and death of organisms. It also includes differentiation and maintenance of cell morphology and function, immunity, stress, cell carcinogenesis and apoptosis^[5,6]。 Wnt signaling pathway is also closely related to tumorigenesis, and it has been reported that it is related to the origin of many tumors^[7,8]It has been found that the Wnt signaling pathway can lead to the occurrence and development of cholangiocarcinoma by activating its downstream target genes. Wnt pathway and its research progress in cholangiocarcinoma are discussed in this paper.