Gastrointestinal glomus tumors: a clinicopathological analysis of fifteen cases / 中华病理学杂志

Objective@#To investigate the clinicopathological features, diagnosis and differential diagnosis of gastrointestinal glomus tumors (GIGT).@*Methods@#Totally 15 cases of GIGT were collected at the First Affiliated Hospital, Zhengzhou University, from January 2011 to June 2018. The clinicopathological features, immunophenotype, BRAF V600E mutation and prognosis were retrospectively analyzed.@*Results@#The 15 patients′ age ranged from 37 to 59 years(median 49 years, mean 50 years). Eleven patients presented with intermittent abdominal pain and distention, three showed antral space-occupying lesions at physical examination, and one had abdominal pain accompanied by fecal blood. Fourteen tumors were located in the stomach, and one was in the ileum. Imaging showed the gastric glomus tumors were located in the submucosal layer with obvious enhancement in the arterial phase, and the ileum glomus tumor involved the whole layer of intestinal wall causing luminal obstruction. The maximum diameters of the tumors ranged from 1.5 to 3.0 cm (mean 2.3 cm). Grossly, the gastric glomus tumors were solid. Microscopically, the gastric glomus tumors were mostly located in the muscularispropria layer and were vascular. The tumor boundary was distinct but without capsule formation. The tumor cells were round or oval, and showed perivascular hemangiopericytoma-like or solid nest-like structures. The tumor cells were mildly pleomorphic, with rare mitosis and no necrosis. Two tumors had focal calcification, two showed mucosal invasion, two showed vascular invasion and five showed perineural invasion. The ileum glomus tumor was cellular, with prominent cellular atypia, and the mitotic count in hot spots was about 5-6/HPF. Immunohistochemistry showed that SMA and collage Ⅳ were strongly expressed in all the tumor cells; caldesmon and calponin were moderately expressed in some regions, and syn was weakly expressed in 12 cases. The Ki-67 proliferation index in the gastric glomus tumors ranged from 1% to 30% (mean 6%); and that in the ileum glomus tumor was about 70%. BRAF V600E mutations were not detected in any of 15 GIGTs. All patients did not receive radiotherapy or chemotherapy post operatively. Thirteen patients were followed up by telephone for 18-90 months (mean 42 months). Twelve patients with gastric glomus tumors survived without recurrence and metastasis, and the patient with ileum glomus tumor had liver metastasis 15 months after operation.@*Conclusions@#Glomus tumors is a rare mesenchymal tumor of the gastrointestinal tract. It should be differentiated from gastrointestinal stromal tumors, neuroendocrine tumor, leiomyoma, solitary fibrous tumor and paraganglioma. Most GIGTs are benign and have good prognosis. More experience is needed to understand the biologic behavior and prognostication of GIGTs.

Pulmonary extranodal NK/T-cell lymphoma, nasal type: a clinicopathological analysis of eleven cases / 中华病理学杂志

Objective@#To investigate the clinicopathological features, diagnosis and differential diagnosis of pulmonary extranodal NK/T-cell lymphoma, nasal type (ENKTL-NT).@*Methods@#Eleven cases of newly diagnosed (10 puncture biopsies and 1 transbronchial biopsy), previously untreated pulmonary ENKTL-NT were collected at the First Affiliated Hospital of Zhengzhou University, from August 2013 to November 2018. The clinicopathological features including histomorphology, immunohistochemistry and in situ hybridization were collected and analyzed.@*Results@#Among the 11 cases, 8 were males and 3 were females, with a male to female ratio of 8∶3.The age range was from 30 to 74 years, with an average of 48 years and a median of 43 years. Tumors involved bilateral lung lobes in 8 cases, the upper left lobe in 1 case, lower left lobe in 1 case, and upper right lobe in 1 case. Main clinical symptoms included fever, often accompanied by cough, and bloody sputum in most cases. All cases were stage Ⅳ E. Histological features included scattered or focal aggregates of marked pleomorphic tumor lymphocytes, accompanied by necrosis and heavy admixture of inflammatory cells. In a few cases, diffuse neoplastic lymphocytes or vascular central and destructive infiltrations were seen. Tumor cells in most cases expressed CD3ε, CD3, CD43, CD56, TIA-1, granzyme B, but did not express CD20, CD79a, and CD5. Ki-67 index ranged from 40%to 90%.All cases were positive for EBER by in situ hybridization. Four of five patients died during follow-up with a survival period of only 1 week to 13 months.@*Conclusions@#Pulmonary ENKTL-NT is rare, high grade malignancy with a poor prognosis. Misdiagnosis is common due to lesional necrosis and heterogeneous cell components. Immunohistochemistry and EBER in situ hybridization are essential for accurate diagnosis.

Tracheobronchopathia osteochondroplastica: a clinicopathological analysis of 18 cases / 中华病理学杂志

Objective@#To investigate the clinical symptoms, imaging features, pathologic manifestations and diagnosis of tracheobronchopathia osteochondroplastica (TO).@*Methods@#The clinical data, imaging and pathologic features and outcome of 18 TO patients diagnosed at the First Affiliated Hospital of Zhengzhou University from August 2011 to August 2018 were collected and analyzed.@*Results@#The 18 TO patients included 10 males and 8 females; patients′ age range was 31 to 64 years (mean 52 years). Six patients (6/18) were smokers. The main presenting clinical symptoms included cough in 15 cases, expectoration in eight cases (8/18), hemoptysis in five cases (5/18), chest tightness in four cases, wheezing in three cases and chest pain in two cases. The time interval between the initial symptoms and diagnosis was 1.5 to 360.0 months, and the average time interval was 45.2 months. Blood calcium and phosphorus were normal in 18 patients (18/18). Chest X-ray showed no direct evidence of TO. Six patients (6/18) showed irregular changes in the trachea or bronchial wall by chest CT scan. Three patients (3/18) had mild ventilatory obstruction. TO was classified as: 10 cases (10/18) were scattered type, seven cases (7/18) were diffuse type and one case (1/18) was confluent type. Epithelial squamous metaplasia, submucosal cartilage, submucosal ossification and hematopoietic bone marrow within the ossified areas were the characteristic histopathologic findings of TO.@*Conclusions@#TO is a rare benign disorder that shows atypical presentation. CT scan is insensitive, the histopathology shows submucosal cartilage or ossification. TO should be diagnosed by comprehensive consideration of clinical symptoms, imaging and pathology.

Clinicopathological features and prognostic factors of primary pulmonary adenoid cystic carcinoma: a study of 59 cases / 中华病理学杂志

Objective@#To investigate the clinicopathological features and prognostic indicators of primary pulmonary adenoid cystic carcinoma.@*Methods@#Fifty-nine cases of primary pulmonary adenoid cystic carcinoma were collected from August 2011 to December 2017 at the First Affiliated Hospital of Zhengzhou University. All cases were retrospectively studied by hematoxylin-eosin staining and immunohistochemistry. The clinicopathological features were reviewed and patient survival analysis was performed using Kaplan-Meier method and Cox regression model. Status of epidermal growth factor receptor (EGFR), KRAS, BRAF genes was analyzed in 15 of the 59 study cases.@*Results@#Among 59 cases, there were 25 males and 34 females with male to female ratio of 1.0 to 1.4. The patient age ranged from 29 to 81 years with a mean age of 55 years. The tumor max diameters ranged from 1.0 to 9.6 cm with an average diameter of 2.8 cm. Fifteen (25.4%) patients were smokers while 44 patients (74.6%) were non-smokers. Tumors predominantly occurred in the trachea (28/59,47.5%), the left main bronchus (7/59,11.9%) and the right bronchus (5/59,8.5%). Grossly, the tumors were well circumscribed, greyish-white nodules. Microscopically the tumor cells were small and uniform, and arranged in tubular, cribriform, and solid patterns. Immunohistochemistry showed that the tumor cells were positive for CK7, S-100 protein, Sox-10, CD117 and p63. TTF1 was only positive in 2 cases and Ki-67 index ranged from 3% to 40%. Eighteen cases (30.5%) were gradeⅠ, 26 cases (40.1%) grade Ⅱ, and 15 cases (25.4%) grade Ⅲ. Overall, 39 cases (66.1%), 7 cases (11.9%), 10 cases (16.9%), and 3 cases (5.1%) were at stages Ⅰ, Ⅱ, Ⅲ, and Ⅳ, respectively. Twenty-three patients (39.0%) received surgical therapy, 3 patients (5.1%) surgery combined with radiotherapy, 9 patients (15.2%) surgery combined with chemotherapy, and 24 cases (40.7%) chemotherapy only. No mutation of EGFR, KRAS and BRAF was detected in all 15 tested cases. The overall survival rate at the first, third and fifth years was 94.9%, 86.4% and 84.7%, respectively. Prognostic analysis showed that patient′s age and tumor size were statistically associated with the survival (P<0.05).@*Conclusions@#Majority of the patients with primary pulmonary adenoid cystic carcinoma are at an early clinical stage with a favorable prognosis. The size of the tumor and the age of the patients are independent prognostic indicators.

Expression and clinical significance of PD-1/PD-Ls in EBV-positive T/NK lymphoprolif-erative disorders / 中国肿瘤临床

Objective: To investigate the expression and clinical significance of programmed death-ligand 1 (PD-L1), programmed death-ligand 2 (PD-L2), and their receptor programmed cell death protein 1 (PD-1) in EBV-positive T/NK lymphoproliferative disease [Epstein-Barr virus-positive T/natural killer (NK)-cell lymphoproliferative disease, EBV(+)-T/NK-LPD]. Methods: The pathological paraffin-embedded tissues of 17 patients with EBV(+)-T/NK-LPD from the First Affiliated Hospital of Zhengzhou University from January 2013 to December 2017 were collected. These patients include 12 males and 5 females, aged 10-82 years old, the average age being 29 years, 4 people in gradeⅠ, 7 in gradeⅡ, 3 in gradeⅢ, and 3 people with hydroa vacciniforme-like lymphoproliferative disorders. Immunohistochemical SP method was used to detect the expression of PD-1, PD-L1, and PD-L2 in human EBV(+)-T/NK-LPD tissues. The relationship between PD-1, PD-L1, PD-L2 expression, and clinicopathological parameters, pathological grades and prognosis were analyzed by Fisher's exact probabilities and Spearman rank correlation. Result: After statistical analysis, the results showed that in 17 cases of tissue samples, there were 12 cases with positive PD-1 expression, 6 cases with positive PD-L1 expression and 5 cases with positive PD-L2 expression. There was no significant correlation between PD-1 and PD-L2 expression and prognosis (P>0.05). PD-L1 expression showed a positive correlation with prognosis (P<0.05). There was no significant correlation between the expression of PD-L1 and PD-L2 with age, sex, as well as LDH and Ki-67 levels (P>0.05). Moreover, there was no significant correlation of PD-1 and PD-L2 expression with pathological grade (r=0.141, r=-0.149, both P>0.05). However, there was a negative correlation between the PD-L1 expression and pathological grade (r=-0.563), and the correlation between the PD-L1 ex-pression and pathological grade was statistically significant (P<0.05). Conclusions: PD-1, PD-L1, and PD-L2 are abnormally expressed in the pathological tissues of EBV(+)-T/NK-LPD. Although there was no significant correlation between the expression of PD-1 and prognosis or pathological grade, it was significantly higher in EBV+T/NK-LPD. PD-1/PD-Ls associated signaling pathway is expected to be a potential new target for EBV(+)-T/NK-LPD immunotherapy.

Gangliocytic paragangliomas: a clinicopathologic study / 中华病理学杂志

Objective@#To investigate the clinicopathological features of gangliocytic paraganglioma(GP).@*Methods@#Clinical data and pathological diagnosis of the 4 cases of GP were obtained through the medical record inquiry from January 2011 to December 2017 at the First Affiliated Hospital of Zhengzhou University. Routine HE staining and immunohistochemistry of CKpan, Syn, CgA, CD56, NSE and NF were performed. Clinical follow-up of the patients was obtained through telephone communication.@*Results@#All 4 patients, including 2 male and 2 female patients, presented with intermittent abdominal pain and distention. The median age was 56 years. Preoperative CT showed local thickening of the duodenum wall with slight enhancement in all four cases. Endoscopic ultrasonography showed low level echo in the mucous layer and submucosa involved by the tumor in 3 of 4 cases. The maximal diameter of the tumor ranged from 0.6 to 1.8 cm with an average of 1.2 cm. Microscopically, the tumors consisted of epithelioid, spindle and ganglion-like cells, and the proportion of the three cell types was different among cases. Epithelioid cells expressed CKpan, Syn, CgA and CD56. Spindle cells expressed S-100 protein and SOX-10 and ganglion-like cells expressed NF, Syn, CgA and CD56.All tumour cells expressed NSE. All 4 patients had no recurrence a post-surgery follow-up period of 3 to 30 months.@*Conclusions@#GP of the duodenum is a benign tumor with excellent prognosis after endoscopic excision. Although its incidence is very low, its diagnosis should be considered for any mass lesion of the duodenum, especially involving mucosa and submucosa of the second dudenal segment.

Expression of BRD4 in squamous cell carcinoma and its effects on cell proliferation and invasion ability / 中华病理学杂志

Objective@#To investigate the expression of BRD4 in squamous cell carcinoma (SCC) tissues and cells, and the effects of its expression on cell proliferation and invasion ability.@*Methods@#Immunohistochemistry was used to detect BRD4 protein expression in SCC tissues and paired normal esophageal squamous epithelial tissues. The expression of BRD4 protein was detected in different SCC cell lines and normal esophageal squamous epithelial cells by Western blot. BRD4 siRNA and control siRNA were used to transfect SCC Eca109 cells, and experiments were divided into three groups: untreated group, control siRNA group and BRD4 siRNA group. Western blot was employed to investigate the expression of BRD4 protein in the three groups of SCC Eca109 cells. CCK-8 kit was utilized to detect cell proliferation ability, and Transwell chamber was used to examine cell invasion ability. Finally, Western blot was used to detect the expression of MMP2 and MMP9 proteins.@*Results@#The positive rate of BRD4 protein expression in SCC tissues was significantly higher than that of normal squamous epithelial tissues. The expression of BRD4 protein in 4 SCC cell lines was higher than that in normal esophageal cell Het-1A. BRD4 siRNA obviously downregulated the expression of BRD4 protein in Eca109 cells, and its downregulation contributed to the suppression of cell proliferation and invasion ability in Eca109 cells (all P<0.05), coupled with the decreases of MMP2 and MMP9 proteins.@*Conclusion@#BRD4 may be closely associated with the proliferation and invasion of SCC, and it thus may be a potential therapeutic target for SCC.

Clinicopathological studies on primary renal lymphoma / 中国肿瘤临床

Objective: To explore the characteristics of clinical pathology, diagnosis, and prognosis of primary renal lymphoma (PRL).Methods: The clinical features, pathological features, immune phenotypes, treatment, and prognosis of 22 patients were retrospectively analyzed. Results: The PRL patients' ages ranged from 2 to 72 years (mean, 54.3 years), of which 13 patients were older than 50 years (59.1%). All of the 22 patients were diagnosed with non-Hodgkin's lymphoma (NHL), including 20 cases of B-cell lymphoma and 2 cases of T-cell lymphoma. Seven patients were still alive and survived for 6-50 months, but the other 15 were dead and survived for only 5-35 months. Conclusion: PRL is uncommon. Clinical manifestations and imaging performance specificity are not obvious. and easily misdiagnosed. Histopathology is still the golden standard for the final diagnosis of this entity. The kidney is most easily involved followed by the bladder. B-cell NHL is the common subtype, and the most common type is the diffuse large B-cell lymphoma. Up to now,no standard regime could be performed for PRL patients. At present, comprehensive therapy, including surgery and chemotherapy, is recommended. For patients with locally advanced or highly aggressive status, therapeutic effect with chemotherapy alone is usually satisfied.

Clinicopathologic analysis of Ewing-like BCOR-CCNB3 undifferentiated sarcoma / 中华病理学杂志

Objective@#To investigate the morphologic, immunohistochemical, genetic, clinical features and prognosis of Ewing-like BCOR-CCNB3 gene fusion undifferentiated sarcoma (BCOR-CCNB3 fusion sarcoma).@*Method@#Seventeen Ewing-like sarcoma cases were screened for CCNB3 expression and BCOR-CCNB3 fusion transcripts by immunohistochemistry and RT-PCR among 260 cases of Ewing-like sarcomas collected during Jan, 2006 to Dec, 2015. Three cases of BCOR-CCNB3 fusion sarcoma were found among 17 atypical Ewing sarcomas, and follow-up were conducted.@*Results@#The harboring of BCOR-CCNB3 fusion transcript was confirmed by RT-PCR and directly sequencing results. The three patients aged between 8 and 11 years old. Two of them were male and the other one was female. One patient achieved a complete response after chemotherapy, the other two died without chemotherapy after surgical excision in 12 months. Tumor cells in all 3 cases showed diffuse nuclear CCNB3, TLE1 and cyclin D1 positivity, while CCNB3 (0/12), TLE1 (1/12) and cyclin D1 (4/12) positivity was infrequent in the 12 cases of classical Ewing′s sarcoma. The oval or plump spindle tumor cells with fine chromatin arranged in solid pattern, the nucleoli was inconspicuous. The delicate capillary networks were obvious in the tumor.@*Conclusion@#With a detailed description of the histological spectrum, immunohistochemical features and clinical characteristic of BCOR-CCNB3 sarcoma, justify distinction from Ewing sarcoma could be possible.

Clinicopathological characterization of 1,058 cases with primary esophageal benign tu-mor in China / 中国肿瘤临床

Objective:To analyze the clinicopathological characterization of primary esophageal benign tumor (EBT). Methods:A total of 1,058 EBTs were enrolled from 500,000 cases in an esophageal and cardiac tumor biological sample and clinical information data-base of Henan Key Laboratory for Esophageal Cancer Research (1973-2015) in the First Affiliated Hospital of Zhengzhou University. SPSS 21.0 software was applied for data analysis. Results:In this database, 1,058 cases with primary EBTs among the 249,246 esopha-geal tumor patients with detailed clinical and pathological information were identified with an incidence of 0.42%(1,058/249,246). A total of 544 patients were male with an average age of 50±11 years old, whereas 514 patients were female, with an average age of 52± 11 years old. Among the 10 types of EBTs, leiomyoma was the most common type (84.50%, 894/1,058), followed by papilloma (6.90%, 73/1058). Adenoma (0.38%, 4/1,058) was the rarest type. Leiomyoma, gastrointestinal stromal tumor, and neurofibroma mainly oc-curred in male patients. By contrast, lipoma, granulosa cell tumor, schwannoma, and hemangioma mainly occurred in female patients.All five cases of hamartoma occurred only in female patients. Given the incidence of≥50%as the common standard, the common EBT in sequence in young male patients was leiomyoma and gastrointestinal stromal tumor, whereas that in young female patients was granulosa cell tumor and lipoma. The common EBT in sequence in older male patients was papilloma, gastrointestinal stromal tumor, and leiomyoma, whereas that in older female patients was schwannoma, papilloma, leiomyoma, gastrointestinal stromal tumor, and hamartoma. Additionally, lipoma, hemangioma, neurofibroma, and adenoma in male patients and neurofibroma in female patients oc-curred in older patients. The different ages of patients with EBTs (P=0.034) and leiomyoma (P=0.004) had a statistical significance. In these EBTs, leiomyoma, papilloma, gastrointestinal stromal tumor, and schwannoma mainly occurred in the middle esophagus, where-as lipoma mainly occurred in the lower esophagus. The major treatment for EBT in the present study was surgery (57.54%, 492/855), which was followed by endoscopic resection (38.01%, 325/855) and others (4.45%, 38/855). Conclusion:The incidence of EBT is low, with a couple of different histological types. Gender, age, and predilection sites are different depending on the histological types of EBTs. Surgery and endoscopic resection are the major treatment methods.

Presence of B-cell clones in angioimmunoblastic T cell lymphoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the significance of B-cell clones in angioimmunoblastic T cell lymphoma (AITL) and the correlation with Epstein-Barr virus (EBV) and prognosis.</p><p><b>METHOD</b>The histopathologic features, T cell clonality and EBV positivity in 33 cases of AITL and 10 cases of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) collected from May 2010 to February 2014 were analyzed by immunohistochemistry, PCR gene rearrangement and in situ hybridization. Follow-up data were also collected.</p><p><b>RESULTS</b>Of the 33 cases with AITL, seven cases (21.2%) exhibited clonal rearrangement of Ig genes; 21 cases (63.6%) were EBV positive. Seven cases had B-cell clones and all (7/7) were EBV positive; 14 of the 26 (53.8%) cases without B-cell clones were EBV positive. The difference between the two groups was statistically significant (P = 0.032). Four levels were made according to the number of EBV-labeled cells, Ig gene rearrangements, but there was no significant difference among levels 1, 2 and 3. There was no correlation between B-cell clones and prognosis (P = 0.263).</p><p><b>CONCLUSION</b>Clonal rearrangement of Ig genes is a common finding in AITL, and it is highly associated with EBV positivity, but not with the number of EBV-labeled cells. The clinical significance remains unclear; further study with more samples is warranted.</p>

Utilization of combined flow cytometry and clonal TCR gene rearrangements in the diagnosis of T-cell lymphoma / 实用医学杂志

Objective To study the usefulness of combined flow cytometry (FCM) and polymerasechain reaction examination for clonal TCR gene rearrangements in the diagnosis of T-cell lymphoma (T-NHL). Methods Histopathologic features, immunohistochemistry, flow cytometric immunophenotyping, cytomorphologic evaluation and TCR gene rearrangements of 32 T-NHL were reviewed retrospectively. The control cases were 18 reactive lesions and 1 histiocytic necrotizing lymphaderitis. Results Out of 32 T-NHL,23 were diagnosed as T-NHL by FCM / TCR gene rearrangements. Of 19 control group, 17 were diagnosed as reactive lesions by FCM / TCR gene rearrangements. The sensitivity, specificity and accuracy were 71.9%, 89.5% and 78.4%, respectively. Conclusions FCM / TCR gene rearrangement is a very important technique in diagnosing T-NHL. Thus, patients with fine needle aspiration cytology can be saved from having an invasive surgery.

Preoperative systemic chemotherapy plus regional intraarterial chemoembolization for patients with locally advanced gastric cancer / 中华普通外科杂志

Objective To investigate the efficacy and safety of preoperative systemic chemotherapy combined with regional intraarterial chemoembolization in the treatment of locally advanced gastric cancer.Methods Clinical data of 158 patients of locally advanced gastric receiving neoadjuvant chemotherapy cancer from January 2008 to July 2012 were retrospectively analyzed.Patients were divided into two groups:those who received preoperative systemic chemotherapy plus regional intraarterial chemoembolization (group A,n =78) and those who received preoperative systemic chemotherapy (group B,n =80).Radical resection was perfomed after 3 to 4 weeks.Results The overall satisfactory rate was significantly higher (60％) in group A compared with 42％ in group B (x2 =6.136,P ＜0.05).The incidence rate of toxicity reaction (except nausea) and postoperative conplications such as anastomotic leakage,intestinal obstruction,poor wound healing,abdominal infection and pulmonary infection were all lower in group A than in group B (all P ＜ 0.05),while the incidence rate of nausea was higher in group A than in Group B (x2 =16.458,P ＜ 0.01).There was no perioperative mortality related to neoadjuvant therapy in two groups.Conclusions Preoperative systemic chemotherapy combined with regional intraarterial chemoembolization was associated with better efficacy,and fewer toxicity reactions and postoperative complications in the treatment of locally advanced gastric cancer.