Clinical characteristics and prognostic characterization of endometrial carcinoma: a comparative analysis of molecular typing protocols.

BACKGROUND: Endometrial carcinoma (EC) is one of the most common gynecological malignancies in China and globally, accounting for the fourth-prevalent cancer in women. Although numerous studies have confirmed prognostic value of The Cancer Genome Atlas (TCGA) molecular subgroups, it is unclear how they are combined with histological features. The main objective of this study was to compare ProMisE and TCGA classification for the rapid and accurate prediction of prognosis within EC patients, together with the provision of a revised strategy for individualized diagnosis and treatment of patients. METHODS: Within this study, 70 patients with EC from Beijing Tsinghua Changgeng Hospital (affiliated to Tsinghua University) were retrospectively examined between July 2015 and December 2021. Samples were processed for determination of clinical markers, together with ProMisE and TCGA classification. RESULTS: Comparative analysis across four TCGA types (POLE, Low-CN, High-CN, and MSI-H) and age, was statistically significant (χ²= 7.000, p = 0.029). There was no significant difference observed among the four TCGA types and FIGO stage, vascular invasion and depth of invasion, or lymph node metastasis and tumor area. There was no significant association between the expression of Vimentin, Ki-67, PTEN, MSH2, PAX-8, ß-catenin, CD10, ER, PR, P16, MLH1, and PMS2 with the four TCGA types. In addition, p63 expression (χ²= 11.09, p = 0.029) and p53 expression (χ²= 11.585, p = 0.005) were statistically significant. Numerous models demonstrated that patients with POLE mutations and low-CN had higher progression free survival (PFS) and overall survival (OS), whereas those with high-CN had lowest values. The log-rank test revealed that the survival rate of PR-positive and ER-positive patients was significantly higher (p < 0.001). CONCLUSION: Overall, these results can be of additional benefit for clinical applications, in comparison to the ProMisE classification method. In addition, PR, ER, vascular infiltration, hyperlipidemia and atherosclerosis were found to be the key factors affecting EC prognosis.

Expert Consensus on Pathological Diagnosis of Intrahepatic Cholangiocarcinoma (2022 version).

Intrahepatic cholangiocarcinoma (iCCA) can originate from the large bile duct group (segment bile ducts and area bile ducts), small bile duct group (septal bile ducts and interlobular bile ducts), and terminal bile duct group (bile ductules and canals of Hering) of the intrahepatic biliary tree, which can be histopathological corresponding to large duct type iCCA, small duct type iCCA and iCCA with ductal plate malformation pattern, and cholangiolocarcinoma, respectively. The challenge in pathological diagnosis of above subtypes of iCCA falls in the distinction of cellular morphologies, tissue structures, growth patterns, invasive behaviors, immunophenotypes, molecular mutations, and surgical prognoses. For these reasons, this expert consensus provides nine recommendations as a reference for standardizing and refining the diagnosis of pathological subtypes of iCCA, mainly based on the 5th edition of the World Health Organization Classification of Tumours of the Digestive System.

Diabetes distress, happiness, and its associated factors among type 2 diabetes mellitus patients with different therapies.

This study aimed to investigate diabetes distress, happiness, and its associated factors of patients with type 2 diabetes mellitus (T2DM) treated by different therapies, and to analyze the related impact factors. A total of 1512 patients with T2DM were randomly selected from 18 tertiary hospitals in Hunan province from January 2016 to April 2016 who has been treated with oral antidiabetics monotherapy, insulin monotherapy, and combination therapy. Use the general information questionnaire, WHO-5 (the World Health Organization 5 well-being index) and PAID (the problem areas in diabetes scale) to collect the data. There are 846 (55.95%) patients that have serious emotional disorders, and the diabetes related distress in insulin treatment group was higher than that in combination treatment group (P < .05). Happiness of T2DM patients in combination therapy was higher than oral antidiabetic drug monotherapy and insulin monotherapy (P < .05). There was a negative correlation between diabetic suffering and happiness in patients with different treatments (R ranged from -0.335 to -0.436, P < .001). Age and happiness experience could explain 14.8% of the variance. Acute and chronic complications, controlled blood glucose level, lifestyle, therapies, and school education can explain 18.3% variance. Under different therapies, the suffering and happiness of T2DM patients differed from each other. The suffering and happiness of T2DM were related to different therapies, age, complications, glycaemic control, lifestyle, school education, and so on.

[Diagnosis and surgical treatment of solitary fibrous tumor of the pelvis].

OBJECTIVE: To explore the clinical diagnosis and surgical treatment of pelvic solitary fibrous tumor (SFT). METHODS: The data of nine cases of pelvic solitary fibrous tumor from April 2008 to February 2012 were reviewed retrospectively. RESULTS: There were 7 male and 2 female patients in this group with a median age of 56 years, of whom 6 were asymptomatic. Their CT showed the tissue density was inhomogencous. Multivisceral resections were performed in 5 patients. Microscopically, the tumor cells were shuttle-shaped, short spindle-shaped or round, and mitoses was rare, immunohistochemistry: CD34, CD99, Bcl-2, Vimentin positive rates were 100%. One patient died 34 months after the surgery, and there was no recurrence in other patients. CONCLUSION: Pelvic SFT is rare. It is difficult to make an accurate diagnosis. Surgery is the most effective therapy. Multivisceral resections are needed sometimes. The prognosis is good for most patients.

[Clinicopathologic features of combined hepatic carcinoma].

OBJECTIVE: To investigate clinicopathological features of combined hepatocellular-cholangiocarcinoma (C-HCC-CC) with neuroendocrine carcinoma (NEC) differentiation and to review the literature. METHODS: The clinical data, histological manifestations and immunohistochemical staining results of two cases of C-HCC-CC were analyzed along with a review of the current literature. RESULTS: Both patients were male with an average age of 57.5 years. Both patients were positive for hepatitis B virus antigen. The tumors of both cases demonstrated the following 3 unequivocal mixed elements: (1) polygonal epithelial tumor cells growing in nests or trabeculae with positive staining for Hepatocyte and AFP, diagnostic of hepatocellular carcinoma (HCC). Cytoplasmic bile production was present in the tumor cells in one case; (2) elliptic or short spindle-shape small blue tumor cells growing in nests or organoid pattern with Syn/CgA/CD56 positivity confirming the presence of neuroendocrine carcinoma (NEC) component; (3) oval tumor cells growing in nests or glandular forms with positivity of CK19 and CK7 confirming differentiation of cholangiocarcinoma (CC). In both cases, the tumors contained at least 20% of each of HCC, NEC and CC components. CONCLUSION: C-HCC-CC with NEC is a rare form of primary malignancy of the liver with a poor prognosis.

[Spontaneous pregnancy in a patient with lymphocytic hypophysitis].

Lymphocytic hypophysitis(LH) is a rare but increasingly recognized autoimmune endocrine condition that causes partial or total hypopituitarism and is often associated with peripartum young women. We here report a 28-year-old patient who had a spontaneous and uneventful pregnancy following LH that had been treated with transspenoidal surgery and followed by anti-inflammatory agent. The woman failed to lactate and developed frontal headaches 3 months after normal delivery of her first child 3 years ago. Lab test showed the reduced concentrations of thyroxine, estradial and cortisol, suggesting hypopituitarism. Magnetic resonance imaging of the brain with contrast was performed and showed a uniformly enhancing pituitary mass with elevated optic chiasm. She underwent transsphenoidal surgery and histological examination of the resected specimen was consistent with lymphocytic hypophysitis. Anti-inflamation was started with prednisolone 40 mg per day because of a recurrence of headache that had completely recovered after surgery and regularly withdrawn to a long term maintenance dose of 10 mg per day. Physiological thyroxine replacement therapy was maintained. Her menstruation was restored without sex hormone replacement after 3 months. Three years after surgery, she got pregnant spontaneously and had normal breastfeeding after delivery. LH did not recur during this peripartum.

[Differential diagnosis of invasive ductal carcinoma versus invasive lobular carcinoma of breast].

OBJECTIVE: To study the diagnostic usefulness of immunohistochemical markers in distinguishing between invasive ductal carcinoma and invasive lobular carcinoma of breast. METHODS: Twenty-four cases of grade I invasive ductal carcinoma, 12 cases of classic invasive lobular carcinoma and 14 cases of invasive carcinoma with mixed ductal and lobular features were retrieved from the archival files of Peking University First Hospital during the period from January, 1998 to December, 2001. Immunohistochemical study for E-cadherin, p120 catenin, epithelia membrane protein 1 (EMP1) and DVL1 was performed. RESULTS: The positivity rates for E-cadherin in grade I invasive ductal carcinoma and classic invasive lobular carcinoma were 83.3% (20/24) and 0, respectively (P < 0.01). The positivity rates for p120 catenin were 100% in both grade 1 invasive ductal carcinoma (membranous staining) and classic invasive lobular carcinoma (cytoplasmic staining). The positivity rates for EMP1 and DVL1 in gradeI invasive ductal carcinoma were 95.8% (23/24) and 54.2% (13/24), respectively; while those in classic invasive lobular carcinoma were 12 and 5 cases, respectively. CONCLUSIONS: E-cadherin and p120 catenin are useful immunomarkers for distinguishing between invasive ductal carcinoma and invasive lobular carcinoma. On the other hand, EMP1 and DVL1 are of limited value in this respect.

[Effect of neoadjuvant chemotherapy on histologic grade and expression of biological markers in breast cancer].

OBJECTIVE: The aim of this study is to investigate the changes of expression of estrogen receptors (ER), progesterone receptors (PR), Her-2, Ki-67 and histological grade after neoadjuvant chemotherapy in breast cancer. METHODS: Sixty-seven patients with histopathalogically confirmed breast cancer by core needle biopsy received neoadjuvant chemotherapy. The effect of neoadjuvant chemotherapy was assessed according to the criteria of the Japanese Breast Cancer Society: non-effective (G1), mildly effective (G2), moderately effective (G3), markedly effective (G4) and completely effective (G5). All pathological slides were retrospectively reviewed. Immunohistochemical staining (EnVision method) was used to detect the expression of ER and PR, Her-2 and Ki-67. The pre- and post-neoadjuvant chemotherapy status of tumor histological grade, ER and PR, Her-2 and Ki-67 expression in the 49 cases were compared. RESULTS: The effect of neoadjuvant chemotherapy was assessed in 67 patients. There were 5 cases (7.5%) in G1, 19 in G2 (28.4%), 20 in G3 (29.9%), 17 in G4 (25.4%) and 6 in G5 (9.0%), respectively. PR positive rate was 71.4% after chemotherapy versus 91.8% before chemotherapy, with a statistically significant reduction (P = 0.021). However, the ER and Her-2 expression before and after neoadjuvant chemotherapy was stable. Of the patients with invasive ductal carcinoma, 28.6% had histological grade change after neoadjuvant chemotherapy, and 85.7% of patients decreased one grade. The proportion of histological grade change in the G1, G2, G3, G4 were 0, 5.9%, 41.2% and 54.5%, respectively (P = 0.013). The average rate of Ki-67 expression decreased from 28.3% pre-chemotherapy to 11.0% post-chemotherapy (P = 0.011). After the neoadjuvant chemotherapy, the Ki-67 expression rate decreased by > 10%, > 20%, > 30%, > 40% and > 50% in 3 groups (G1 and G2, group G3, group G4 and G5) showed a tendency to be increased, with a significant difference (P < 0.05). CONCLUSION: PR expression in breast cancer decreases after neoadjuvant chemotherapy, while ER and Her-2 expressions remain stable. After neoadjuvant chemotherapy, the histological grade and proliferation index are decreased and correlated with the response to chemotherapy. Therefore, histological grade and proliferation index may be effective complementary factors in assessment of the effectiveness of neoadjuvant chemotherapy.

[Expression of proline-rich tyrosine kinase-2 in human primary colorectal carcinoma and its prognostic implication].

OBJECTIVE: To investigate the expression of proline-rich tyrosine kinase-2 (Pyk2) in human primary colorectal carcinoma (CRC) and it's prognostic significance. METHODS: The expression of Pyk2 was retrospectively examined with immunohistochemistry (IHC) in 108 tissues of primary CRC. The correlation of Pyk2 expression to prognosis and relevant clinical factors were analyzed. RESULTS: The rate of Pyk2 low-expression in CRC was 56.5% (61/108). The expression of Pyk2 correlated significantly to the histological grade (P < 0.05) and the TNM stage (P < 0.05), while no correlation between Pyk2 expression and age, tumor size (P > 0.05). Patients with Pyk2 over-expression had significantly higher 5-year survival rate (66.0%) than those with Pyk2 low-expression (31.4%). Pyk2 expression, together with carcinoma histologic grade and TNM stage were prognostic factors to CRC on the multivariate analysis. CONCLUSIONS: Pyk2 expression can be a prognostic factor to the CRC patients together with other predictors.

[One patient with Kimura's disease and angiolymphoid hyperplasia with eosinophilia also suffers from kidney injury].

OBJECTIVE: Reporting a rare case with Kimura's disease and angiolymphoid hyperplasia with eosinophilia (ALHE), who also has nephrotic syndrome resulting from minimal change glomerulopathy. METHODS: Histological manifestations, immunohistochemical staining, immunofluorescence staining, and electron microscope were performed. RESULTS: One 37-year-old male patient with recurrent erythra, cutaneous node, painless cervical lymph node enlargement and nephrotic syndrome in 5 years. It's confirmed through biopsies that the subcutaneous node is ALHE, the cervical lymph node is kimura disease, and renal lesion is minimal change glomerulopathy. CONCLUSION: Kimura disease and ALHE may be different features of the same disease, and may complicate glomerulopathy.

[Comparative study of heterogeneity of extranodal and nodal diffuse large B cell lymphoma].

OBJECTIVE: Primary nodal and extranodal diffuse large B-cell lymphoma (DLBCL) were investigated for the heterogeneity of histopathology and immunophenotype, and their relation to clinical stage, comparatively. Whether E2F1 can be used as a germinal center B cell (GCB) DLBCL marker was also discussed. METHODS: Classification of histopathology and immunophenotype of 98 cases were studied by immunohistochemistry in tissue microarray. RESULTS: Histopathologic morphology presented as: centroblastic (CB,88.8%, 87/98), immunoblastic (IB,5.1%, 5/98), anaplastic (ALCL,3.1%, 3/98), and T cell rich B cell lymphoma (TCRBCL,3.1%, 3/98). Of which, 31 cases were GCB DLBCL, 10 (20.8%, 10/48) nodal, and 21 extranodal (42%, 21/50, P=0.024). The rates of Stages I/II in nodal and extranodal area were 48.5% and 70%, respectively (P=0.015). The rate of Stage I/ II in GCB DLBCL (74.2%) were higher than in non-GCB DLBCL (50.7%, P=0.029). The CD10 positive rates were 36.8% and 17.1% in Stages I/II and III/IV, respectively, and had significant differences (P=0.033). The CD10 positive rates were 18.8% and 38% in nodal and extranodal area, respectively (P=0.035). The positive rates of E2F1 were 38.8% and 16.5% in GCB and non-GCB DLBCL, respectively, and had significant differences (P=0.016). The positive rate of E2F1 had positive relation with the expression of CD10 and Bcl-6 (P<0.05). CONCLUSION: CB is the most type in 98 cases of DLBCL. The rate of GCB DLBCL was significant higher in extranodal than in nodal areas CD 10 can be used as a prognostic marker. The prognosis of GCB DLBCL is better than that of non-GCB DLBCL. The positive expression of E2F1 can be used as a marker of GCB DLBCL.

[An analysis of the clinical and radiological features of bronchioloalveolar carcinoma].

OBJECTIVE: To describe the clinical and radiological features of bronchioloalveolar carcinoma. METHODS: Data of 1 050 inpatients of lung cancer, including 50 cases of pathology-proven bronchioloalveolar carcinoma, diagnosed in our hospital between 1993 and 2003, were retrospectively reviewed. The clinical information of all the patients and the HRCT findings of 31 cases of bronchioloalveolar carcinoma were analyzed. RESULTS: There was a female predominance (60%) in the 50 patients with bronchioloalveolar carcinoma. Cough was the most common presenting symptom (20/50). Twenty-four patients sought medical attention because of abnormal chest X-rays, most of which were of nodular type at the early stage. Twenty patients were completely asymptomatic at presentation. Out of the 31 cases with HRCT, eight were of the miliary type. "Bubble-like lucency" and calcifications inside nodules were present in 7 cases respectively out of the 11 cases of the nodular type. There were 9 cases each with low attenuation consolidation, pseudocavities, reticular shadowing and ground-glass opacities. The signs of "crazy paving" and "CT angiogram sign" (distinct vasculature at the background of low-attenuated consolidation at the peak of contrast scanning) were found in 2 cases. CONCLUSIONS: Bronchioloalveolar carcinoma accounted for 4.76% of lung carcinoma in our series, with a female predominance. High prevalence of asymptomatic patients at presentation and unusual long course should prompt regular chest X-ray examination. The characteristics of HRCT findings are very helpful in its diagnosis and differential diagnosis.

[Helicobacter pylori genotypes of gastrointestinal B cell lymphoma].

OBJECTIVE: To assess the expression of specific virulence-associated Helicobacter pylori (Hp) genotypes. (cag A, vac A, and ice A status) in primary gastrointestinal B cell lymphoma. METHODS: Forty-nine paraffin wax embedded tissues were analyzed by immunohistochemical staining and polymerase chain reaction. RESULTS: There were 14 cases of mucosa associated lymphoid tissue lymphoma (MALT-L) (8 in stomach, and 6 in intestine) and 35 cases of diffuse large B cell lymphoma (DLBCL) (21 in stomach, and 14 in intestine) in all. The positive rates of vac A s1, vac A s2, vac A m2, ice A 1 and cag A were 50.0%, 42.9%, 50.0%, 14.3% and 85.7% in MALT-L; 57.1%, 40.0%, 25.7%, 5.7% and 91.4% in DLBCL, respectively. CONCLUSION: High toxicity cag A+Hp strains seem to play a role in the pathogenesis of gastrointestinal B cell lymphoma, whereas vac A m2 may be more associated with MALT-L. Clinical stage was not associated with virulence-associated Hp genotypes.

[Expression of proline-rich tyrosine kinase-2 (Pyk2) in gastric carcinoma and its significance].

OBJECTIVE: To investigate whether proline-rich tyrosine kinase-2 (Pyk2) is expressed differently in normal gastric mucosas and gastric carcinoma tissues and further to evaluate its significance. METHODS: Expressions of Pyk2 in 59 cases of normal gastric mucosas and 52 cases of gastric carcinoma tissues were analysed by immunohistochemical methods. RESULTS: Immunohistochemical studies showed that the positive rates of Pyk2 protein expression in normal gastric mucosas and gastric carcinoma tissues were 86.44% (51/59) and 19.23% (10/52) respectively. The difference between normal gastric mucosas and gastric carcinoma tissues was statistically significant (P<0.05). The positive rates of Pyk2 expression in highly differentiated gastric carcinoma and moderately/lowly differentiated gastric carcinoma were 47.37% (9/19) and 3.03% (1/33) respectively. Statistically significant differences (P<0.05) were observed in the levels of Pyk2 expression between highly differentiated gastric carcinoma and moderately/lowly differentiated gastric carcinoma. The positive rates of Pyk2 expression at different TNM stages gastric carcinoma were respectively: stage I 66.67% (6/9), stage II 30% (3/10), stage III 3.45% (1/29), stage IV 0% (0/4). The differences were statistically significant [(II+III+IV) v I, chi2=15.767, P<0.05]. CONCLUSION: In this study, we demonstrate that Pyk2 is expressed in normal gastric mucosas, whereas its expression declines significantly or almost disappears in gastric carcinoma tissues. The expression of Pyk2 progressively decreases with increasing grade of malignancy and TNM stages of gastric carcinoma. This phenomenon indicates that Pyk2 expression may be involved in the generation and development of gastric carcinoma.

[Proliferation and apoptosis in primary gastrointestinal B-cell non-Hodgkin s lymphoma and its association with Helicobacter pylori].

OBJECTIVE: To investigate primary gastrointestinal B-cell non-Hodgkin s lymphoma for clinicopathological features, proliferation, apoptosis and its association with Helicobacter pylori (HP). METHODS: Classification of tumors, expression of HP, proliferation and apoptosis related gene products were studied by immunohistochemistry. Apoptosis was studied by TUNEL (TdT [terminal deoxynucleotidyl transferase] dUTP nick end-labeling). RESULTS: There were 15 cases of mucosa associated lymphoid tissue (MALT) lymphoma (9 in stomach, 6 in intestine) and 42 cases of diffuse large B cell lymphoma (DLBCL) (28 in stomach, 14 in intestine) in all the 57 cases of primary gastrointestinal BCL. The average apoptotic indexes (AI) were 0.16%, 2.54% in MALT lymphoma and DLBCL respectively. The average proliferation indexes (PI) were 2.22% and 8.71%,respectively. The p53 positive rates were 6.7% and 35.7%. PI (P=0.026) and p53 (P=0.044) had significant differences; But Bcl-2 positive rates were 60.0% and 35.7%,and HP positive rates were 66.7% and 23.8%, respectively. HP had significant differences (P=0.005). CONCLUSION: HP and gastrointestinal MALT lymphoma had significant relation. Apoptosis and proliferative activity were higher in DLBCL than in MALT. The higher Bcl-2 expression in MALT may be related to lower apoptosis. p53 promotes apoptosis and p53 gene mutation may play a role in the progression from MALT to DLBCL. HP antibody may be used in HP detection in gastrointestinal BCL.

[Retrospective analysis of 304 cases of malignant lymphomas in pathology: study and practice of the WHO classification of lymphoid neoplasms].

OBJECTIVE: To evaluate the practical application of the WHO classification of lymphoid neoplasms, and to investigate the relative frequency and geographic distribution of the subtypes of lymphoma. METHODS: The pathological specimens of 304 cases with lymphoma diagnosed during the period 1994 approximately 2002 in the First Hospital of Peking University were retrospectively studied. The histopathologic, immunophenotypic and clinical data were reviewed and reappraisal was performed according to the WHO classification. RESULTS: There were 20 cases (6.6%) of Hodgkin's lymphoma (HL) and 284 cases (93.4%) of non-Hodgkin's lymphoma (NHL). In the 284 NHL cases, B-cell neoplasms accounted for 60.2% and T/NK-cell neoplasms for 39.1%. On subtyping, diffuse large B-cell lymphoma, extranodal NK/T cell lymphoma of nasal type, unspecified peripheral T-cell lymphoma, extranodal marginal zone B-cell lymphoma of MALT type, angioimmunoblastic T-cell lymphoma and follicular lymphoma were the most common 6 subtypes and amounted to 88.03% of NHL. The distribution of NHL subtype in this group showed important difference from those in some areas in the world. Extranodal NK/T cell lymphoma of nasal type and other peripheral T-cell lymphoma had a higher frequency, but B-small lymphocytic lymphoma and follicular lymphoma were less common in this group than in Western countries. CONCLUSION: The new WHO classification may be applicable to the diagnosis and subtyping of most lymphomas, making the pathological diagnosis easier to practise. A correct diagnosis of ML may be reached by combination of clinic, histological and immunological features.