[Risk factor analysis of lymph node metastasis in endometrial carcinoma combined with molecular types].

Objective: To investigate the relationships between molecular types of the cancer genome atlas (TCGA) of patients with endometrial carcinoma (EC) and lymph node metastasis and other clinicopathological features. Methods: The clinical pathological information of 295 patients with EC who underwent initial inpatient surgical treatment and accepted the detection of the molecular types of TCGA with next-generation sequencing technology at Peking University People's Hospital were collected during April 2016 and May 2022. The TCGA molecular typing of EC was divided into four types: POLE-ultramutated (15 cases), high microsatellite instability (MSI-H; 50 cases), copy-number low (CNL; 175 cases), and copy-number high (CNH; 55 cases). The differences of clinical pathological features among different molecular types and the risk factors of lymph node metastasis were analyzed retrospectively. Results: Among 295 patients with EC, the average age was (56.9±0.6) years. (1) There was a statistically significant difference in lymph node metastasis (0, 8.0%, 10.3% and 25.5%) among the four molecular types (χ2=12.524, P=0.006). There were significant differences in age, stage, pathological type, grade (only endometrioid carcinoma), myometrium invasion, lymphatic vascular space infiltration, and estrogen receptor among the EC patients of four molecular types (all P<0.05). Among them, while in the patients with CNH type, the pathological grade was G3, the pathological type was non-endometrioid carcinoma, and the proportion of myographic infiltration depth ≥1/2 were higher (all P<0.05). (2) Univariate analysis suggested that pathological type, grade, myometrium infiltration depth, cervical interstitial infiltration, lymphatic vascular space infiltration, and progesterone receptor were all factors which significantly influence lymph node metastasis (all P<0.01); multivariate analysis suggested that the lymphatic vascular space infiltration was an independent risk factor for lymph node metastasis (OR=5.884, 95%CI: 1.633-21.211; P=0.007). (3) The factors related to lymph node metastasis were different in patients with different molecular types. In the patients with MSI-H, the non-endometrioid carcinoma of pathological type was independent risk factor for lymph node metastasis (OR=29.010, 95%CI: 2.067-407.173; P=0.012). In the patients with CNL, myometrium infiltration depth≥1/2 (OR=4.995, 95%CI: 1.225-20.376; P=0.025), lymphatic vascular space infiltration (OR=14.577, 95%CI: 3.603-58.968; P<0.001) were the independent risk factors for lymph node metastasis. While in the CNH type patients pathological type of non-endometrioid carcinoma (OR=7.451, 95%CI: 1.127-49.281; P=0.037), cervical interstitial infiltration (OR=22.938, 95%CI: 1.207-436.012; P=0.037), lymphatic vascular space infiltration (OR=9.404, 95%CI: 1.609-54.969; P=0.013), were the independent risk factors for lymph node metastasis. Conclusions: POLE-ultramutated EC patients have the lowest risk of lymph node metastasis, and CNH patients have the highest risk of lymph node metastasis. The risk factors of lymph node metastasis of different molecular types are different. According to preoperative pathological and imaging data, lymph node metastasis is more likely to occur in patients with non-endometrioid carcinoma in MSI-H and CNH type patients, and lymph node metastasis is more likely to occur in patients with myometrium infiltration depth ≥1/2 in CNL type patients.

[Significance of molecular classification in fertility-sparing treatment of endometrial carcinoma and atypical endometrial hyperplasia].

Objective: To investigate the molecular classification of endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH) treated with fertility-sparing therapy, and to analyze its relationship with clinicopathological factors and treatment efficacy. Methods: A total of 46 EC and AEH patients who received fertility-sparing therapy and molecular classification tested by next generation sequencing in Peking University People's Hospital from June 2020 to December 2021, were retrospectively collected. The relationships between molecular classification and clinicopathological factors and treatment outcomes were analyzed. Results: (1) Of the 46 patients, including 40 EC and 6 AEH patients, 32 cases (71%, 32/45) had complete response (CR) after treatment, with median CR time of 8 months, 6 cases (13%, 6/45) had partial response, and 8 cases (25%, 8/32) had recurrence. (2) The cases were distributed as no specific molecular profile (NSMP) 34 cases (74%, 34/46) subtype mainly, high microsatellite instability (MSI-H) 7 cases (15%, 7/46), POLE ultra-mutated 3 cases (7%, 3/46), and copy number high (CNH) 2 cases (4%, 2/46). Patients with CNH had the hightest serum cancer antigen 125 (CA125) level [(34.3±35.2) kU/L]. MSI-H subtype had more family history of tumors (6/7), more with loss of mismatch repair (MMR) protein expression by immunohistochemical (7/7), and higher nuclear antigen associated with cell proliferation (Ki-67) expression level (3/3). (3) Patients in MSI-H subgroup had the lowest CR rate at 6 months (0/6; P=0.019), and survival analysis showed that they were less likely to achieve CR than those with NSMP subtype (P=0.022). Subgroup analysis of patients with NSMP showed that age ≥30 years related with longer treatment time to CR (P=0.010). In addition, CR was obtained after treatment in 2/3 POLE ultra-mutated cases and 2/2 CNH, respectively. Conclusions: Molecular classification relates with the treatment response in patients with EC and AEH treated with fertility-sparing therapy. Patients with MSI-H subtype have poor treatment efficacy, and patients with NSMP need to be further studied and predict treatment benefit. However, there are few cases in POLE ultra-mutated and CNH subtypes, which need further clinical research.

[Clinical and immunological characteristics of 88 cases of overlap myositis].

OBJECTIVE: To investigate the clinical and immunological characteristics of overlap myositis (OM) patients. METHODS: The data of 368 patients with idiopathic inflammatory myopathies (IIMs) admitted to Peking University People's Hospital from January 2004 to August 2020 were analyzed retrospectively, including demographic characteristics, clinical characteristics (including fever, Gottron' s sign/papules, Heliotrope rash, V-sign, Shawl sign, Mechanic' s hands, skin ulceration, periungual erythema, subcutaneous calcinosis, dysphagia, myalgia, myasthenia, arthritis, Raynaud' s phenomenon, interstitial lung disease, pulmonary hypertension and myocardial involvement), laboratory characteristics, immunological characteristics [including antinuclear antibodies, rheumatoid factors, myositis-associated autoantibodies (MAAs) and myositis-specific autoantibodies (MSAs)] and survival. The clinical and immunological characteristics and prognostic differences of OM and non-OM were compared. The Kaplan-Meier and Log Rank methods were used to analyze the survival. RESULTS: A total of 368 patients were included. 23.9% (88/368) of IIMs patients were OM patients. Among the 88 OM patients, 85.2% (75/88) of them were female, and the median interval between disease onset and diagnosis was 13.5 months. The incidence of overlapped connective tissue diseases in the OM patients was dermatomyositis (DM) in 60.2%, polymyositis (PM) in 3.4%, immune-mediated necrotizing myopathy (IMNM) in 2.3% and anti-synthetase syndrome (ASS) in 34.1%. Compared with the non-OM patients, the proportion of the females in the OM patients was higher (85.2% vs. 72.1%, P=0.016), the OM patients had longer disease duration [13.5(4.5, 48.0) months vs. 4.0(2.0, 12.0) months, P < 0.001]. As for clinical characteristics, compared with the non-OM patients, the incidence of V-sign (25.0% vs. 44.6%, P=0.001) and periungual erythema (8.0% vs. 19.6%, P=0.013) were lower; the incidence of Raynaud's phenomenon (14.8% vs. 1.8%, P < 0.001), interstitial pneumonia (88.6% vs. 72.1%, P=0.001), pulmonary hypertension (22.7% vs. 7.5%, P < 0.001) and myocardial involvement (18.2% vs. 9.3%, P=0.033) were higher. As for immunological characteristics, compared with the non-OM patients, the incidence of elevated aspartate aminotransferase (AST) (31.8% vs. 45.0%, P=0.035) was lower and elevated C-reactive protein (CRP) (58.0% vs. 44.6%, P=0.037) was higher; the positive rates of antinuclear antibodies (ANA) (85.1% vs. 63.4%, P=0.001) and rheumatoid factors (RF) (40.2% vs. 17.8%, P < 0.001) and anti-Ro-52 (71.6% vs. 56.1%, P=0.038) in serum were higher. There was no significant difference in the survival between the OM patients and non-OM patients. CONCLUSION: Pulmonary hypertension and myocardial involvement were frequently observed in OM.

[Value of histopathological growth pattern in predicting 3-year progression free survival after operation in patients with liver metastasis of colorectal cancer].

Objectives: To investigate the value of histopathological growth patterns (HGP) in predicting the 3-year progression free survival (PFS) after resection the liver metastasis from patients with colorectal cancer. Methods: The clinicopathological data of the 111 patients with liver metastasis of colorectal cancer diagnosed at Peking University People's Hospital, Beijing, China from January 2007 to January 2017 were analyzed. After excluding the patients who did not meet the inclusion criteria, a total of 80 patients were analyzed. According to the international expert consensus on HGP, the HGP types of liver metastasis were evaluated. The correlation between HGP and other clinicopathological factors was analyzed using χ2 or Fisher test. Kaplan-Meier survival curve was used to examine 3-year PFS in the patients with liver metastasis of colorectal cancer by HGP. The independent risk factors of 3-year post-resection PFS were determined using univariable and multivariable analyses. Results: A total of 80 cases were analyzed, including 43 cases of desmoplastic type (54%), 32 cases of replacement type (40%), 3 cases of pushing type (4%), and 2 cases of mixed type (2%). There was no correlation of HGP with age, gender, time of metastasis, tumor burden, histological grade, mucous differentiation or microsatellite instability. The 3-year post-resection PFS of the patients with desmoplastic type was significantly longer than that of patients with replacement type. The univariable and multivariable analyses showed that HGP was an independent prognostic factor. Conclusions: The HGP of colorectal cancer metastases to the liver mainly present as desmoplastic and replacement types. HGP is an independent prognostic factor for the patients with liver metastasis of colorectal cancer after resection of the metastasis. Therefore, HGP should be clearly indicated in the pathological report to help guide clinical treatments.

[Clinicopathological and molecular features of small round cell sarcoma of bone and soft tissue: a study of 72 cases].

Objective: To investigate the clinicopathological, immunohistochemical and molecular features of small round cell sarcoma (SRCS) of the bone and soft tissue, and to compare the diagnostic value of different techniques. Methods: Seventy-two cases of SRCS of the bone and soft tissue diagnosed at People's Hospital, Peking University from January 2016 to March 2020 were recruited and retrospectively analyzed for pathological morphology, immunophenotype and fluorescence in situ hybridization (FISH) data. Next generation sequencing (NGS) was performed on 13 difficult cases. Results: In the study cohort, the patients ranged in age from 4-55 years, with a male predominance. The most Ewing's sarcomas and osteosarcomas occurred in the bone, while CIC-rearranged sarcomas, BCOR-rearranged sarcoma, synovial sarcoma, extraskeletal myxoid chondrosarcoma and FUS-NFATc2 rearranged sarcoma occurred in soft tissue. Histologically, all cases were composed predominantly of small round cells. Most cases were positive for vimentin and CD99, and showed a variable reactivity for neurogenic markers. Muscle marker and epithelial marker were negative for most cases. Combined with clinical features, histopathologic findings, immunophenotype, FISH and NGS, we diagnosed 46 Ewing sarcomas, 14 osteosarcomas, 3 CIC-rearranged sarcomas, 1 BCOR-rearranged sarcoma, 1 synovial sarcoma, 1 clear cell soft tissue sarcoma, 1 extraskeletal myxoid chondrosarcoma, 1 FUS-NFATc2 rearranged sarcoma, and 4 undifferentiated small round cell sarcomas. Conclusions: SRCS of bone and soft tissue is a group of malignant mesenchymal tumors based on morphological features. Most cases can be diagnosed with a combination of clinical characteristics, morphological features and immunohistochemical phenotype, while some cases require such further tests as FISH and NGS technologies, and NGS can be useful in diagnosing and categorizing SRCS.

[Analysis of prognosis and pregnancy outcomes of fertility-preserving treatment for patients with stage â a, grade 2 endometrial cancer].

Objective: To investigate the efficacy and pregnancy outcome of fertility-preserving treatment for patients with stage Ⅰa, grade 2 endometrial cancer (EC). Methods: Clinical data was retrospectively collected for EC or atypical endometrial hyperplasia (AEH) patients treated in Peking University People's Hospital, Foshan First People's Hospital of Guangdong Province and First Affiliated Hospital of Sun Yat-sen University, from 2010 to 2019. Inclusion criteria for fertility-preserving treatment included: (1) Age ≤45 years. (2) EC with histological differentiation of G(1), G(2) or endometrial AEH. (3) EC disease should be stage Ⅰa, confined to the endometrium without myometrial invasion, lymph node or extrauterine metastasis. Treatment regimen: patients were given oral progestin therapy and endometrial pathology was evaluated every three months. Patients were divided into three groups as G(2) EC group, G(1) EC group and AEH group based on the histological differentiation. Oncological and pregnancy outcomes were compared among them. Results: (1) Totally 57 eligible patients were included in this study, including 11 cases with G(2) EC, 22 cases with G(1) EC, and 24 cases with AEH. (2) Oncological outcome: among the three groups of G(2) EC, G(1) EC and AH, the complete remission rates (9/11, 91% and 96%, respectively) and recurrence rates (3/9, 30% and 22%, respectively) were not significantly different (all P>0.05). Median remission time was significantly longer in the G(2) EC group than those in the other two groups (8, 6 and 4 months; P=0.046). Among 9 G(2) EC patients who recurred after complete remission, three patients relapsed at 7, 18 and 53 months, respectively. All 3 patients chose fertility-sparing treatment again, and all achieved complete remission after retreatment. (3) Pregnancy outcome: among the three groups, the assisted reproduction technology rates (4/8, 5/18 and 36%, respectively) and pregnancy rates (6/8, 5/18 and 36%, respectively) had no significant difference (P>0.05). However, time interval to pregnancy was shorter in G(2) EC patientsthan the other two groups (4, 9 and 22 months, respectively; P=0.006). Conclusions: Fertility-preserving treatment for patients with stageⅠa, G(2) endometrial cancer, may obtain a relatively high remission rate and an acceptable pregnancy rate. However, further exploration is needed due to the limited number of cases.

[Clinicopathological features of myeloid sarcoma and DLBCL in the breast: a comparative study].

Objective: To study the clinicopathological features, diagnosis and differential diagnosis of myeloid sarcoma of the breast. Methods: Ten cases of myeloid sarcoma (MS) and 19 cases of diffuse large B cell lymphoma (DLBCL) of the breast were selected from Peking University People's Hospital from February 2005 to September 2019. The cases were evaluated by microscopy and immunohistochemistry basing on WHO classification (2008 and 2017). Results: For the 10 cases of MS, the mean and median age was 33.8 and 31 years (range 23 to 47 years) respectively. All patients presented with breast masses; six presented with B symptoms (6/10); and LDH level was elevated in four patients. The largest tumor dimension was 1.0 to 5.3 cm (mean 2.7 cm). All 10 patients had history of acute myeloid leukemia (AML), and in one patient, the AML occurred after chemotherapy for hydatidiform mole. One case was classified as M0, four were M2, two were M4 and three were M5. For the AML, all patients received chemotherapy and nine were treated by allogeneic hematopoietic stem cell transplant (allo-HSCT) and the breast masses occurred4 months to 2 years post-transplant. Using Ann Arbor staging, five cases were stage Ⅰ, three were stage Ⅱ, and 2 were stage Ⅳ. The MS was found in the left breast (two cases); right breast (three cases) and both breasts (five cases). Lymphocyte in peripheral blood, B symptom and site of lesion had statistical significance between myeloid sarcoma and DLBCL(P<0.05). The tumor cells were primitive, expressing MPO, CD43, CD117, etc. All ten patients had follow-up information, and the median survival period was 14.4 months (range 1 to 50 months). Seven patients died. The prognosis of patients with MS was worse than DLBCL(P=0.002). Conclusions: The clinical history, pathologic morphology, immunophenotyping and molecular studies are very important for diagnosing MS tumors in the breast, and MS may occur after allo-HSCT for AML. Tumor resection, chemotherapy, radiotherapy and donor lymphocyte infusion are recommended for treatment. The prognosis is poor.

[Significance of micropapillary histopathological subtype of thyroid carcinoma].

Objective: To study the clinical and pathologic factors of papillary thyroid microcarcinoma (PTMC) and its significance as a histopathologic subtype of papillary thyroid carcinoma (PTC). Methods: A retrospective study of 719 patients with non-high-risk PTMC who underwent surgery for the first time in the Peking University People's Hospital from January 2007 to June 2019 was conducted, the relationship between clinicopathologic factors and lymph node metastasis, and the expression of four tumor markers CK19, HMBE1, Galectin-3 and CD56 by immunohistochemistry were evaluated. Some comparisons were made with PTC. Results: The peak patients' age was 40-49 years for both non-high-risk PTMC and PTC; the lymph node metastasis rate was higher in the 30-39 years age group than the 50-59 years age group (P<0.05); the lymph nodes metastasis rate was significantly higher for multiple lesions than for single lesion (P<0.05). Lymph node metastasis rate of PTMC with capsular invasion was significantly higher than those without (P<0.05). There was no significant correlation between lymph node metastasis of PTMC and patients' gender, tumor location, tumor size, and lymphocytic thyroiditis. The expression rates of CK19, HMBE1 and Galectin-3 both in PTMC and PTC were 100%, and the expression rates of CD56 were 25.6% (85/332) and 20.0% (70/350) respectively. Conclusion: As the main pathologic subtype of PTC, a variety of clinicopathologic factors of PTMC are related to lymph node metastasis, and it is highly recommended to pay close attention to PTMC. The expression of tumor marker CD56 alone cannot be used as a basis to exclude PTMC and PTC.

[Analysis of the clinical features and misdiagnosis reasons of 17 patients misdiagnosed with IgG4-related disease].

OBJECTIVE: To summarize the clinical characteristics of patients misdiagnosed with IgG4-related disease, to analyze the reasons of misdiagnosis and to improve the clinical recognition of the disease. METHODS: The general data, clinical manifestations, laboratory examination results and pathological features of 17 patients with IgG4-related diseases misdiagnosed outside the hospital were retrospectively analyzed. RESULTS: Among the 17 patients, there were 9 males and 8 females with a median age of 45 years, and the median time from onset to diagnosis was 12 months. Most patients' initial admission department was not rheumatology or immunology department. Six of the 17 patients were eventually diagnosed with lymphoproliferative disease, 4 with autoimmune disease, and 2 with infectious disease, Rosai Doffman disease, desmofibromatosis, highly differentiated mucoepidermoid carcinoma of the bottom of the mouth, hypereosinophilic syndrome, asthma and allergic rhinitis in 1 case each. The typical sites of IgG4-related disease were involved in 14 patients, including 6 cases of parotid gland, 2 cases of submandibular gland, 3 cases of pancreas and 2 cases of retroperitoneal lesions. Serum IgG4 was elevated in 10 patients, serum IgG4/IgG value was higher than 10% in 7 patients, serum IgE was increased in 7 patients, complement was decreased in 4 patients, and eosinophilic granulocytes were increased in 3 patients. Pathological biopsy was performed in 15 patients, and infiltration of lymphocyte was observed in 10 patients, IgG4+ plasma cells were present in 5 patients, the ratio of IgG4+ plasma cells to IgG+ plasma cells was less than 40% in 4 patients and greater than 40% in 1 patient. However, none of the 15 patients had the storiform pattern of fibrosis and obliterative phlebitis. CONCLUSION: A variety of diseases can perform as IgG4-related disease witih typical sites involved, elevated serum IgG4, even can be characterized by pathological IgG4+ plasma cells infiltration. Physicians should pay attention to the differential diagnosis and comprehensively evaluate the patient's clinical manifestations, and laboratory results. Timely and even repeated pathological biopsy is also needed for definite diagnosis.

[Clinicopathological study of SET subtype of ovarian high-grade serous carcinoma].

Objective: To investigate the clinicopathological characteristics and significance of solid, endometrioid and transitional (SET) ovarian high-grade serous carcinoma (HGSC). Methods: A total of 408 cases of ovarian HGSC admitted to Peking University People's Hospital from January 2011 to September 2016 were collected. (1) According to the proportion of tumors with SET form in all tumors, they were divided into three groups: HGSC-classic group (<25%), HGSC-SET Ⅰ (25%-50%) and HGSC-SET Ⅱ (>50%) group. The clinical and pathological characteristics of three groups of ovarian HGSC patients were compared respectively. (2) According to the growth pattern, that was, the proportion of pushing/expanding invasive tumors in the whole pelvic disseminated tumors of pelvic disseminated tumors, the three groups were divided into four subgroups: group A (0-25%), group B (26%-50%), group C (51%-75%) and group D (>75%). Differences in progression-free survival (PFS) among the four subgroups in each group were compared respectively. Results: The median age of 408 cases with ovarian HGSC was 63.3 years (47-78 years), including 152 cases premenopausal and 256 cases postmenopausal. Among 408 cases of ovarian HGSC, 290 cases were in HGSC-classic group, 91 cases in HGSC-SET Ⅰ and 27 cases in HGSC-SET Ⅱ group. (1) There were significant differences in age, proportion of menopausal patients, tumor necrosis (including map necrosis or acne necrosis), response rate to primary chemotherapy, 5-year mortality rate and PFS between HGSC-SET Ⅰ and HGSC-SET Ⅱ (P<0.05). There was no significant difference among the above indexes between HGSC-SET Ⅰ and HGSC-SET Ⅱ (P>0.05). In HGSC-classic group, HGSC-SET Ⅰ and HGSC-SET Ⅱ, the proportion of family members or patients with history of epithelial ovarian cancer or breast cancer increased in turn, and the detection rate of serous tutal intraepithelial carcinoma (STIC) in fallopian tube tissue decreased in turn. There were significant differences between the two groups (P<0.05). (2) In HGSC-classic group, there were 147 cases in group A, 124 cases in group B and 19 cases in group C (0 case in group D), with median PFS of 17.4, 17.7 and 16.5 months respectively (P<0.05); 10, 6, 29 and 46 cases in group A, B, C and D in HGSC-SET Ⅰ, with median PFS of 9.6, 12.7, 30.1 months and 39.0 months respectively, which there were significant difference among group A and C and D (all P<0.05); among group B, C and D group in HGSC-SET Ⅱ, there were respectively 3, 12 and 12 cases (0 case in group A), and the median PFS was 13.5, 34.2 and 47.8 months (P<0.05). PFS was positively correlated with the increase of push/expansive infiltration ratio. Conclusions: The detection rate of STIC in ovarian HGSC patients with SET is higher, the effect of primary chemotherapy is better, and PFS is prolonged. PFS was significantly prolonged in patients with pelvic disseminated tumors of HGSC-SET, the infiltration of which were predominated by pushing or expanding boarder.

[Combined application of immunohistochemical markers to identify pathologic subtypes of ampullary carcinoma and its clinical significance].

Objective: To investigate the expression of immunomarkers CK7, CK20, CK17, CDX2, MUC1 and MUC2 in primary adenocarcinoma of the ampulla of Vater, to explore the role of these markers in the histopathologic subclassification of ampullary carcinoma; and to provide biologic basis for precision treatment of patients with different types of ampullary carcinoma. Methods: Forty-two cases of primary ampullary carcinoma were collected at Peking University People's Hospital, from 2012 to 2018 year. There were 22 males and 20 females. Aged range 42 to 88 years old, with mean aged (62±11) years. Among the patients, 6 was high differentiation, 19 median differentiation, and 17 low differentiation. Immunohistochemical studies on the expression of CK7, CK20, CK17, CDX2, MUC1 and MUC2 were performed in 42 cases of primary ampullary carcinoma. The relationship between different ampullary carcinoma subtypes and clinicopathologic survival data was analyzed using SPSS 16.0 statistical software. Results: Three histopathologic subtypes were observed. Among 42 cases, 8(19.0%)were classified as intestinal subtype, which showed a positive expression rate of 8/8 for both CK20 and CDX2, and 5/8 for MUC2. Both CK7 and CK17 were weakly expressed in one case (1/8). No expression was observed for MUC1 in this subtype. Twenty-two (52.4%,22/42) cases were classified as pancreaticobiliary subtype, which showed a positive expression rate of 100.0%(22/22) for both CK7 and MUC1, and 90.9% (20/22) for CK17. No expression was observed for CK20, CDX2 and MUC2.The remaining 12 (28.6%) cases were classified as mixed subtype, which showed variable expression patterns. The expression frequencies of these 6 immunomarkers in different subtypes of ampullary carcinoma did not correlate with various clinicopathologic factors such as patient gender and age, tumor size, histologic differentiation, pancreatic and bile duct invasion, or the depth of duodenal invasion. However, stage Ⅲ+Ⅳ diseases were more commonly seen in pancreaticobiliary type (63.6%,14/22) than intestinal type (2/8) and mixed type (3/9; χ(2)=6.508, P=0.039). Follow-up data showed a trend of better survival rate for patients with intestinal subtype than those with mixed and pancreaticobiliary subtypes. Conclusions: Ampullary carcinoma can be subclassified into three different subtypes using a panel of six immunomarkers, especially for the identification of subtypes of poorly differentiated carcinoma. CK7, CK17 and MUC1 are major markers of pancreaticobiliary subtype, whereas CK20, CDX2 and MUC2 are useful markers for intestinal subtype. The mixed subtype variably expresses these markers. The prognosis of patients with intestinal subtype appears better than that of pancreaticobiliary and mixed subtypes. Accurate subtyping of ampullary carcinoma is clinically important to patient management and prognosis assessment.

[Microcystic, elongated and fragmented invasion pattern in endometrial carcinoma: the clinicopathology analysis].

Objective: To assess the clinical value for the clinicopathological features of microcystic elongated and fragmented (MELF) invasion in endometrial carcinoma (EEC) . Methods: The clinicopathological data of 108 cases of endometrial carcinoma with total hysterectomy, bilateral adnexectomy, and pelvic dissection were retrospectively analysis in Peking University People's Hospital from April 2015 to October 2016. Twenty-five patients with endometrial carcinoma showing MELF invasion pattern were collected. We analyzed retrospectively the association of MELF pattern invasion with clinical pathology data and prognosis of the patients, partial immunohistochemical staining was implemented. MELF invasion was a special invasion pattern and characterized by microcystic, elongated, fragmented (composed of cluster cells) gland in muscular layer. Results: The incidence rate was 23.1% (25/108). These patients mean age was (59.3±10.9) years old. Four cases were premenopausal, and 21 were postmenopausal. Abnormal vaginal bleeding was the main clinical presentation. The lesions tend to appear adjacent to the tumor body. Sometimes, it may be appears away from the tumor body in the deep muscle layer.Lymph node metastasis were present in 5 cases (20%, 5/25). Thirteen cases (52%, 13/25) of them demonstrated lymph vascular space involvement (LVSI). The immunohischemical expression of ER,PR, Ki-67 and galectin-3 showing MELF invasion pattern were weaker than no showing MELF invasion pattern endometrial carcinoma, cktokeratin (CK) was showed diffuse strong positive expression, E-cadherin was moderately positive expression. All 25 cases were followed up for (23.2±5.9) months (14-33 months) after the therapy with no recurrence on metastasis. Conclusions: MELF invasion pattern is a special invasion pattern in low-grade EEC. The incidence of LVSI and lymph node metastasis rate in endometrial carcinoma with MELF invasion are significantly increased. The prognosis of MELF invasion pattern may be poor.

[Analysis of proliferative lesions of haematopoietic and lymphoid tissue in the female productive tract].

Objective: To study the clinicopathologic features, diagnosis and differential diagnosis of tumors of haematopoietic and lymphoid tissue in the female productive tract. Methods: Eleven cases of myeloid sarcoma and leukemia, 9 of non Hodgkin lymphoma (NHL) , 13 of cervical lymphoma-like lesions were selected from Peking University People's Hospital from January 2006 to August 2017. According to WHO classification of tumors of haematopoietic and lymphoid tissues (2008) and updated classification(2016), the cases were studied by microscopy, immunohistochemistry and in situ hybridization. Results: In 20 cases of tumors of haematopoietic and lymphoid tissue, the mean and median age was 48.5 and 56 years old (range: 16-77 years old) . In cases of lymphoma-like lesion of uterine cervix, the mean and median age was 45.9 and 48 years old (range: 23-62 years old) . The patients with neoplasm present as fever, fatigue, hypogastralgia, colporrhagia and mass etc. Eight cases had history of acute myeloid leukemia, and 3 had myeloid leukemia while pregnancy. One case of chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) had history of ovary small cell carcinoma and high grade serous carcinoma resected with chemotherapy. One case of diffuse large B cell lymphoma (DLBCL) had history of renal transplantation. Lactic dehydrogenase (LDH) was elevated in 9 cases (9/18) . The cases of lymphoma-like lesion present as contact bleeding in most cases and all located in cervix. Four cases of neoplasm located in vulva, 1 in vagina, 4 in cervix, 4 in uterine corpus, 8 in ovary and 2 in placenta. Clinical staging of NHL: 4 case was stageⅠ, 1 case of stageⅢ, and 4 cases of stage Ⅳ. Pathological morphology: 9 cases were myeloid sarcoma, 2 cases were placenta invaded by myeloid leukemia. Six cases were DLBCL, and 1 case was CLL/SLL, 1 case was mucosa associated lymphoid tissuse lymphoma (MALToma) , and 1 case was anaplastic large cell lymphoma. Resected mass, chemotherapy was performed in tumors of haematopoietic and lymphoid tissue. Five cases of myeloid sarcoma and 2 of NHL died. In 13 cases of lymphoma-like lesion of uterine cervix, the general condition was good as following up. Conclusions: The clinical history, pathological morphology and immunohistochemistry are very important for diagnosing tumors of haematopoietic and lymphoid tissue in the female productive tract. Resection with chemotherapy is recommended in treatment. The prognosis of lymphoma-like lesion of uterine cervix is good, and should be differentiated from lymphoma.

Direct uterine sampling using the SAP-l sampler device to detect endometrial lesions during histopathological examination.

AIMS: To evaluate the sampling adequacy and diagnostic accuracy of the endometrial SAP-l sampling device in detecting endometrial lesions based on histopathological examination. MATERIALS AND METHODS: In total, 182 patients who required an endometrial biopsy were enrolled in this study. All of the patients underwent endometrial biopsies with the SAP-l sampler prior to hysteroscopy (169/182) or dilatation and curettage (D&C) (13/182). Endometrial tissues were obtained at biopsy for histopathological examination. RESULTS: Ad- equate endometrial specimens were obtained in 148 of 182 patients (81.32%). Menopause (p = 0.000), endometrial thickness (p = 0.004), and the types of endometrial diseases (p = 0.009) differed significantly between the two groups. Among the 169 patients who underwent hysteroscopy, sampling scratches were observed in the uterine cavity in 147 cases (86.98%). Compared to traditional methods, such as hysteroscopy and D&C, the sampling diagnostic sensitivity, specificity, and positive and negative predictive values were 82.35%, 100%, 100% , and 97.76% for endometrial carcinoma (n=17) and 37.5%, 100%, 100% and 97.76% for endometrial atypical hyperplasia (n=8), respectively. Those that were misdiagnosed occurred because the lesions were focal or localized in a small part of the uterine cavity. The sampling diagnostic sensitivity for polyps (n=32) was 12.5%. Two patients with submucosal leiomyoma went undiagnosed based on the sample specimens. CONCLUSION: Endometrial sampling using the SAP-l sampler is a minimally invasive altemative technique for obtaining adequate endometrial specimens for histopathological examination. The SAP-l sampler was useful in detecting endometrial carcinoma and atypical hyperplasia cases that were not highly suspected to be localized; however, this method was not useful in detecting endometrial polyps and submucosal leiomyomas.

[Fluorescence in situ hybridization combined with cytomorphology for the detection of lung cancer in bronchial brushing specimens].

Objective: To evaluate the diagnostic value of fluorescence in situ hybridization (FISH) combined with bronchial brushing cytology for detecting lung cancer. Methods: Centromeric enumeration probes (CEPs) for chromosomes 7, 8 and 17 were used in FISH assay. The combination of FISH and cytology was analyzed in 69 bronchial brushing specimens. Results: The positive rates of CEP7, CEP8 and CEP17 in malignant cases diagnosed by cytology were 50.0%, 80.8% and 65.4%, respectively. CEP8 probe showed significantly higher positive rate than CEP7 (P=0.015). In the samples of suspicious of malignancy, the positive rates of CEP7, CEP8 and CEP17 were 46.6%, 66.7% and 58.8%, respectively. While in atypical cases, the positive rates of these three probes were 20.0%, 33.3% and 25.0%, respectively. There was no statistical difference between suspicious of malignancy and atypical cases (P>0.05) as well as between malignant and suspicious of malignancy (P>0.05). No chromosome aberrations were found in normal cases diagnosed by cytology. The positive rates of these three probes in adenocarcinoma (ADC) were slightly higher than those in squamous cell carcinoma and small cell lung cancer. However, only CEP8 probe showed statistically difference between ADC and small cell lung cancer (P=0.044). The combination of cytology and FISH using any one of the three-probe set (CEP7, CEP8 and CEP17) showed the sensitivity and specificity of 80.3% and 100.0%, while those of cytology were 54.1% and 100.0%, respectively. Conclusions: FISH combined with cytomorphology assisted the cytology diagnosis of suspicious of malignancy and atypical cases. Therefore, it significantly improved the diagnostic sensitivity for lung cancer without sacrificing specificity.

[Tumors of lymphoid and hematopoietic tissue of spleen: a clinicopathologic analysis of 53 cases].

Objective: To study the clinicopathologic features, diagnosis and differential diagnosis of the tumors of lymphoidand hematopoietic tissue of the spleen(TLTS). Methods: Fifty-three cases of TLTS were selected from the pathologic files from Peking University People's Hospital from April 2002 to April 2017. According to WHO classification of tumors of hematopoietic and lymphoid tissues (2008) and its updated classification (2016), the cases were studied by microscopy, immunohistochemistry and in situ hybridization, combined with the bone marrow biopsy and clinical examination. Results: In 53 cases of TLTS, the male to female ratio was 3.4∶1.0; the mean age was 55.4 years (range 21-76 years), and all patients presented with variable degree of splenomegaly. Laboratory examination showed increased percentage of lymphocyte in peripheral blood in 22 cases, and elevated serum LDH level in 24 cases. Abnormal blood counts were seen in 26 cases pre-operatively, in which 22 cases showed complete or partial correction of these abnormalities post-operatively (84.6%, 22/26). The clinical symptoms included abdominal pain or distension, fatigue, fever, and weight loss, etc. Seventeen cases presented with lymphadenopathy of abdomen or other sites. Bone marrow biopsy was performed in 30 cases, and 19 cases were involved by tumor (63.3%). Of all 53 cases, 43 were diagnosed as primary splenic lymphoma (PSL), and the remaining 10 cases as secondary TLTS. According to Ann Arbor staging, 14 cases were stages Ⅰ or Ⅱ, 6 were stage Ⅲ and 28 were stage Ⅳ. By histopathologic classification, 43 cases of PSL were splenic B-cell marginal zone lymphoma (SMZL; 48.8%, 21/43), diffuse large B cell lymphoma (DLBCL; 23.3%, 10/43), splenic diffuse red pulp small B-cell lymphoma (11.6%, 5/43), mantle cell lymphoma (9.3%, 4/43), follicular lymphoma (4.7%, 2/43), and composite lymphoma (CL, DLBCL and classical Hodgkin lymphoma; 2.3%, 1/43). The remaining 10 cases were chronic lymphocytic leukaemia/small lymphocytic lymphoma (4 cases), hairy cell leukaemia (1 case), hepatosplenic T-cell lymphoma (HSTL; 5 cases), with lesions in other sites. Of the 53 cases of TLTS, 47 were B cell neoplasm (88.7%, 47/53), and the T cell neoplasms were all HSTL(5 cases, 9.4%, 5/53), 1 case was composite lymphoma. In 11 cases of TLTS, EBER in situ hybridization was performed and all cases were negative. Forty eight cases had follow-up data, and the median survival period was 17.0 months(range: 1-96 months). The survival of patients with SMZL and DLBCL were 25.7 and 18.6 months respectively. Thirteen patients died (27.1%, 13/48). The prognosis of those with elevated LDH level, high clinical stage, B symptoms and older than 60 years of age was worse. And the prognosis of DLBCL was worse than that of SMZL. There was no statistically significant difference between these factors and prognosis (P>0.05). Conclusions: Most TLTS cases present with splenomegaly and abnormal blood counts, and complete or partial remission of blood counts isseen after splenectomy. The most common pathologic types of TLTS are SMZL and DLBCL. Definite diagnosis of TLTS could be made by combining clinical features, histopathology, immunophenotype, genetics, bone marrow biopsy and laboratory examination.