Pathological evaluation of endoscopic submucosal dissection for early gastric cancer and precancerous lesion in 411 cases / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the pathological characteristics of endoscopic submucosal dissection (ESD) specimens for early gastric cancer and precancerous lesions, accumulating experience for clinical management and pathological analysis.@*METHODS@#A total of 411 cases of early gastric cancer or precancerous lesions underwent ESD. According to the Japanese guidelines for ESD treatment of early gastric cancer and classification of gastric carcinoma, the clinicopathological data, pathologic evaluation, concordance rate of pathological diagnosis between preoperative endoscopic forceps biopsies and their ESD specimens (in 400 cases), as well as the risk factors of non-curative resection of early gastric cancer, were analyzed retrospectively.@*RESULTS@#23.4% (96/411) of the 411 cases were adenoma/low-grade dysplasia and 76.6% (315/411) were early gastric cancer. The latter included 28.0% (115/411) non-invasive carcinoma/high-grade dysplasia and 48.7% (200/411) invasive carcinoma. The concordance rate of pathological diagnosis between endoscopic forceps biopsies and ESD specimens was 66.0% (264/400), correlating with pathological diagnosis and lesion location (P < 0.01). The rate of upgraded diagnosis and downgraded diagnosis after ESD was 29.8% (119/400) and 4.2% (17/400), respectively. Among the 315 cases of early gastric cancer, there were 277 cases (87.9%) of differentiated type and 38 cases (12.1%) of undifferentiated type. In the study, 262 cases (83.2%) met with absolute indication, while 53 cases (16.8%) met relative indication. En bloc and curative resection rates were 98.1% and 82.9%, respectively. Risk factors for non-curative resection included a long diameter >20 mm (OR=3.631, 95%CI: 1.170-11.270, P=0.026), tumor infiltration into submucosa (OR=69.761, 95%CI: 21.033-231.376, P < 0.001)and undifferentiated tumor histology (OR=16.950, 95%CI: 4.585-62.664, P < 0.001).@*CONCLUSION@#Several subjective and objective factors, such as the limitations of biopsy samples, the characteristics and distribution of the lesions, different pathological understanding, and the endoscopic sampling and observation, can lead to the differences between the preoperative and postoperative pathological diagnosis of ESD. In particular, the pathological upgrade of postoperative diagnosis was more significant and should receive more attention by endoscopists and pathologists. The curative resection rate of early gastric cancer in ESD was high. Non-curative resection was related to the long diameter, the depth of tumor invasion and histological classification. ESD can also be performed in undifferentiated early gastric cancer if meeting the indication criteria. The comprehensive and standardized pathological analysis of ESD specimens is clinically important to evaluate the curative effect of ESD operation and patient outcomes.

Analysis of microsatellite instability in endometrial cancer: The significance of minimal microsatellite shift / 北京大学学报(医学版)

OBJECTIVE@#To analyze the differences and characteristics of microsatellite instability (MSI) in endometrial cancer (EMC), by using colorectal cancer (CRC) as control.@*METHODS@#In the study, 228 cases of EMC were collected. For comparative analysis, 770 cases of CRC were collected. Mismatch repair (MMR) expression was detected by immunohistochemistry (IHC), and microsatellite instability (MSI) was analyzed by PCR and capillary electrophoresis fragment analysis (MSI-PCR). MSI-PCR was detected using five mononucleotide repeat markers: BAT-25, BAT-26, NR-21, NR-24, and MONO-27.@*RESULTS@#In EMC, we found 27.19% (62/228) of deficient mismatch repair (dMMR) using IHC, significantly higher than CRC (7.79%, 60/770). Meanwhile, subclonal expression of MMR protein was found in 4 cases of dMMR-EMC and 2 cases of dMMR-CRC. According to the criteria of major micro-satellite shift, we found 16.23% (37/228) of MSI-high (MSI-H), 2.63% (6/228) of MSI-low (MSI-L), and 81.14% (185/228) of microsatellite stability (MSS) in EMC using MSI-PCR. The discor-dance rate between MMR-IHC and MSI-PCR in EMC was 11.84% (27/228). In CRC, we found 8.05% (62/770) of MSI-H, 0.13% (1/770) of MSI-L, and 91.82% (707/770) of MSS. The discordance rate between MMR-IHC and MSI-PCR in CRC was only 0.52% (4/770). However, according to the criteria of minimal microsatellite shift, 12 cases of EMC showed minimal microsatellite shift including 8 cases of dMMR/MSS and 4 cases of dMMR/MSI-L and these cases were ultimately evaluated as dMMR/MSI-H. Then, 21.49% (49/228) of EMC showed MSI-H and the discordance rate MMR-IHC and MSI-PCR in EMC decreased to 6.58% (15/228). No minimal microsatellite shift was found in CRC. Compared with EMC group with major microsatellite shift, cases with minimal microsatellite shift showed younger age, better tumor differentiation, and earlier International Federation of Gynecology and Obstetrics (FIGO) stage. There were significant differences in histological variant and FIGO stage between the two groups (P < 0.001, P=0.006).@*CONCLUSION@#EMC was more prone to minimal microsatellite shift, which should not be ignored in the interpretation of MSI-PCR results. The combined detection of MMR-IHC and MSI-PCR is the most sensitive and specific method to capture MSI tumors.

Analysis of diagnosis and treatment of 100 patients with Hürthle cell adenoma / 北京大学学报(医学版)

OBJECTIVE@#To summarize and analyze the clinical data and prognosis of the patients with Hürthle cell tumor (HCT) in order to raise the clinicians' awareness of the disease.@*METHODS@#The clinical data on patients with histopathologically proven HCT, without other thyroid carcinomas, were collected retrospectively in Peking University First Hospital from January 2001 to February 2017. All the patients underwent surgery due to thyroid nodules. The follow-up information was also collected.@*RESULTS@#A total of 100 patients were enrolled in the current study. All of them were diagnosed with Hürthle cell adenoma (HCA). There were 77 females and 23 males, with the male-to-female ratio of 1 : 3.3. The average age of these patients was (52±14) years at the time of operation. Fifty-one patients were found their thyroid nodules accidentally by ultrasonography during their health check-ups. 69.4% of the 49 symptomatic patients presented with painless cervical nodules. 83.0% HCA patients were combined with multinodular goiters (MNGs). 88.4% (76/86) patients were euthyroid and 53.8% (21/39) had increasing thyroglobulin levels. The mean longest diameter of HCAs was (3.2±1.5) cm (range: 0.9-7.3 cm) on ultrasonography. There were a series of sonographic features of HCA, such as larger, solidity, hypoecho, a smooth outline, intranodular vascularization, perinodular vascularization, absence of calcification in nodules and absence of enlarged cervical lymph nodes. Compared with the histological diagnosis, the diagnostic accuracy by frozen section (FS) during operation was 97.4%. Twenty-nine patients were followed up with an average period of (49.2±22.1) months and none of them had local recurrence or cervical lymph node metastasis. Six patients accepted thyroid hormone replacement treatment and one had thyrotoxicosis due to over-dose.@*CONCLUSION@#HCA is more common in women. It is often found accidentally by ultrasonography during their health check-ups or presented with painless cervical nodules. It is combined with MNG frequently. HCA exhibits numerous sonographic features but not unique. FS during operation is a reliable method to identify HCA with high diagnostic accuracy. Patients with thyroid hormone administration should be monitored for thyroid function after thyroid surgery.

Characteristics of lymph node metastasis and evaluating the efficacy of endoscopic submucosal dissection in early gastric cancer / 北京大学学报(医学版)

OBJECTIVE@#To investigate the correlation between clinicopathological features and lymph node metastasis, and to evaluate the feasibility and efficacy of endoscopic submucosal dissection (ESD) in early gastric cancer (EGC) by comparing with surgery treatment.@*METHODS@#The clinicopathological data of 320 patients with EGC who were treated in Peking University First Hospital between January 2010 and December 2017 were retrospectively reviewed, in which there were 198 cases of surgical procedure and 122 cases of ESD. Characteristics of lymph node metastasis in EGC were analyzed, and lymph node metastasis of EGC with ESD absolute and expanded indications were summarized. The long-term efficacy of ESD and surgical treatment of EGC were compared to evaluate the rationality of absolute and expanded indications of ESD.@*RESULTS@#Lymph node metastasis was detected in 22 (11.1%) of 198 patients. Univariate analysis showed a positive relationship between tumor size (χ2=5.525, P=0.019), depth of invasion(χ2=8.235, P=0.004), histological type (χ2=6.323, P=0.012), lymphovascular invasion (χ2=12.273, P < 0.001) and lymph node metastasis in EGC. Multivariate analysis revealed that depth of invasion(Wald=7.575, P=0.006) and histological type (Wald=6.317, P=0.012) were independent relative factors of lymph node metastasis in EGC. The lymph node metastasis rates of the patients with absolute and expanded ESD indications were both 0%. The 5-year survival rates of the patients who met ESD absolute indication receiving surgery treatment and ESD were 97.6% and 97.9% respectively, and the difference between the two groups was not statistically significant(χ2=0.014, P=0.907).The 5-year survival rates of the patients who met ESD expanded indication receiving surgery treatment and ESD were 96.5% and 91.7% respectively, the difference between the two groups was not statistically significant(χ2=1.061, P=0.303).@*CONCLUSION@#Lymph node metastasis in EGC is mainly correlated with depth of invasion and histological type. Our data indicate that ESD procedure for EGC is comparable to surgery in terms of long-term efficacy in both absolute and expanded indications. However, some studies of a large sample size are still needed for more confirmation.

Diagnosis and treatment of seven primary mediastinal yolk sac tumors / 北京大学学报(医学版)

OBJECTIVE@#Primary mediastinal yolk sac tumor, which is also known as endodermal sinus tumor, is a rare but lethal neoplasm and its prognosis is very dismal. The current treatment for this tumor is controversial, and chemotherapy combined with resection of residual lesions is adopted sometimes. We summarized the experience of seven primary mediastinal yolk sac tumors treated with platinum-based chemotherapy and extended resection in Peking University First Hospital.@*METHODS@#Clinicopathological data of the patients with primary mediastinal yolk sac tumor who received operation in Peking University First Hospital between August 2014 and August 2018 were collected and analyzed retrospectively.@*RESULTS@#We experienced seven primary mediastinal yolk sac tumors during this period. Computed tomography scan revealed an anterior mediastinal tumor in all the patients and all of them had markedly raised alphafetoprotein (AFP) and normal β-human chorion gonadotropin (β-HCG). Five patients underwent needle core biopsy before treatment, which showed a mediastinal yolk sac tumor. All of these patients received preoperative platinum-based chemotherapy and they all presented partial response according to computed tomography. Two other patients did not receive preoperative biopsy, so they directly underwent extended resection. All of the seven patients underwent operation successfully and two of them experienced postoperative complications, including one with pneumonia and the other with atelectasis. R0 resection was achieved in six patients and R1 resection was achieved in the other patient. According to postoperative pathology, there were one microcyst subtype, one adenoid subtye, one giant capsule subtype and two hybrid subtypes. Surprisingly, there were no yolk sac tumor tissue in the other two patients after preoperative chemotherapy. All the patients received postoperative chemotherapy, excluded one patient who was unable to tolerate chemotherapy after operation. Three patients experienced postoperative pulmonary metastases within one year and two of them died soon. The other patient received chemotherapy and immunotherapy after recurrence and he was alive at the time of writing. Four other patients were alive without recurrence and metastasis.@*CONCLUSION@#Primary mediastinal yolk sac tumor is rare and its prognosis is poor. A multimodality approach including adjuvant chemotherapy and resection of residual lesions is the optimal treatment and it may lead to long-term survival.

A retrospective analysis of 12 cases of primary thyroid lymphoma / 北京大学学报(医学版)

OBJECTIVE@#To discuss the clinical characteristics and diagnostic and therapeutic considerations of primary thyroid lymphoma (PTL) by reviewing PTL cases.@*METHODS@#In the study, 12 cases of PTL diagnosed and treated in Peking University First Hospital between January 1995 and September 2015 were identified. The clinical characteristics, management experiences and prognosis of these cases were reviewed retrospectively.@*RESULTS@#A total of 12 PTL patients (four males and eight females) were collected, with an average age of 63 years (42 to 81 years) at the time of diagnosis. The average time to clarify diagnosis was 5 months (0.5 to 24 months). Eleven patients presented with a rapidly growing neck mass and visited surgical department, except one complained of coughing and suffocated. Seven patients were hypothyroid, and four were euthyroid at the time of diagnosis. In sonography of 11 cases, nine showed bilateral nodules, with an average diameter of 3.87 cm. Pathologic diagnosis of non-Hodgkin's lymphoma was confirmed in all the 12 cases by means of partial thyroidectomy (four) or core needle biopsy (eight). The pathological subtypes were diffuse large B cell lymphoma in nine patients, mucosa-associated lymphoid tissue lymphoma (MALToma) in two, and small B cell lymphoma in the other one patient. Five patients were concomitant with Hashimoto's thyroiditis. Eleven patients received chemotherapy. Only one patient did not have any further treatment after operation due to an inertia type of tumor. The median overall survival time was 24 months (1-117 months), three patients died. Among the patients who survived, seven completed chemotherapy without disease progression, one MALToma case did not receive chemotherapy after thyroidectomy but was still alive with PTL, and one patient just finished his second course of chemotherapy.@*CONCLUSION@#The diagnosis of PTL should be considered when dealing with rapidly growing goiters in elder female Hashimoto's thyroiditis patients whose B ultrasound indicates hypoechogenicity in thyroid nodules or parenchyma, especially with lymphadenopathy and tracheal compressions. Timely use of coreneedle biopsy on suspicious cases can avoid unnecessary surgical trauma, and chemotherapy is the main treatment.

Cell block technology in the pathological diagnosis of pleural effusion / 中国组织工程研究

BACKGROUND: Cytologic smear is a routine detection method for pleural effusion, but the results are far from satisfactory. Therefore, pleural effusion is made into cell block for immunochemistry and gene detection, to improve the detection accuracy, which contributes to the treatment and prognosis of pleural effusion. OBJECTIVE: To explore the application value of cell block technology in the pathological diagnosis and molecular detection of pleural effusion. METHODS: Totally 105 cases of pleural effusion samples were collected at Department of Pathology, Peking University First Hospital between January 2016 and August 2017. Effective components extracted after centrifugation were used to make paraffin blocks for hematoxylin-eosin staining and immunocytochemical staining thereafter. Genetic mutations were further detected in the cases of lung cancer diagnosed by cytology.RESULTS AND CONCLUSION: The positive rate of routine cytological smear was 30.5% (32/105), which was significantly lower than that of the cell block section (44.8%, 47/105). The positive rate of immunocytochemical staining combined with cell block was the highest one with 57.1%, 60/105). Besides, this method could be used to identify tumor types. Gene mutation detection was performed in 19 cases of lung cancer, among which 13 cases were positive. These results indicate that cell block technology combined with immunocytochemical staining is an effective method for the diagnosis of malignancy and tumor origin in pleural effusion, and can be further used for mutation detection.