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.

Amelanotic metastatic gastric malignant melanoma: a case report.

Melanoma is a malignant form of cutaneous cancer with an increasing incidence since 1970s, accounting for nearly 75% of the death related to skin cancer especially in western countries. Highest recurrence and mortality were observed for the subtype with distal metastasis, demonstrating poor outcomes. However, high incidence of gastrointestinal metastasis of malignant melanoma is frequently misdiagnosed due to lack of specific clinical manifestations, especially for the rare observed cases presented amelanotic appearance, accounting for about 2% of all metastatic cases. In the present study, we reported a 36-year-old male patient, who was firstly diagnosed as gastric cancer, and then was confirmed as amelanotic melanoma metastasis by pathological examination, demonstrating positive for melanoma markers including Melan A, S-100, Hmb45 and CD79a. In conclusion, for the amelanotic neoplasm observed during gastroscopy in patients with melanoma history, pathological examination should be carried out to confirm the possibility of melanoma metastasis, providing evidences for the following treatment.

A standardized pathological proposal for evaluating microvascular invasion of hepatocellular carcinoma: a multicenter study by LCPGC.

BACKGROUND AND AIMS: Microvascular invasion (MVI) is a key pathological factor that severely affects the postoperative prognosis of patients with hepatocellular carcinoma (HCC). However, no MVI classification schemes based on standardized gross sampling protocols of HCC are available at present. METHODS: 119 HCC specimens were sampled at multiple sites (3-, 7-, and 13 points) for the optimum MVI detection rate. 16,144 resected HCCs were graded as M0, M1 or M2 by adopting three-tiered MVI grading (MVI-TTG) scheme based on the seven-point sampling protocol (SPSP). Survival analyses were performed on 2573 patients to explore the advantages of MVI-TTG. RESULTS: The MVI detection rate determined by SPSP was significantly higher than that determined by the 3-point sampling method (34.5% vs. 47.1%, p = 0.048), but was similar to that determined by the 13-point sampling method (47.1% vs. 51.3%, p = 0.517). Among 16,144 resected HCCs, the proportions of M0, M1 and M2 specimens according to SPSP were 53.4%, 26.2% and 20.4%, respectively. Postoperative survival analysis in 2573 HCC patients showed that the 3-year recurrence rates in M0, M1 and M2 MVI groups were 62.5%, 71.6% and 86.1%, respectively (p < 0.001), and the corresponding 3-year overall survival (OS) rates were 94.1%, 87.5% and 67.0%, respectively (p < 0.001). M1 grade was associated with early recurrence, while M2 grade was associated with both early and late recurrence. MVI-TTG had a larger area under the curve and net benefit rate than the two-tiered MVI grading scheme for predicting time to recurrence and OS. CONCLUSIONS: SPSP is a practical method to balance the efficacy of sampling numbers and MVI detection rates. MVI-TTG based on SPSP is a better prognostic predictor than the two-tiered MVI scheme. The combined use of SPSP and MVI-TTG is recommended for the routine pathological diagnosis of HCC.

Primary hepatic neuroendocrine tumor case with a preoperative course of 26 years: A case report and literature review.

Primary hepatic neuroendocrine tumor (PHNET) is an extremely rare liver tumor. Patients often have no clinical symptoms or have only non-specific symptoms, such as abdominal pain and abdominal mass. The clinical manifestations, disease development, treatment methods, and treatment outcomes of PHNET vary greatly among cases. Here we report a case of PHNET with a confirmed 26-year survival before surgery. The patient was a 56-year-old female. A large right hepatic mass was detected when the patient was 30 years old. The tumor could not be removed during exploratory laparotomy, and constriction of the right hepatic artery and biopsy were conducted. Pathological results indicated a diagnosis of benign tumor, but a confirmed diagnosis was not reached. Twenty-six years after the patient had been living with the tumor, she sought treatment again because of tumor progression. After systematic evaluation of the resectability, the tumor was resected. Based on the examination results of the gastrointestinal tract and lungs, intraoperative examination results, pathological findings, and long-term follow-up results, the diagnosis of PHNET was confirmed. This case represents the longest reported survival time for a PHNET patient before removal of the tumor.

Differentiation between pancreatic metastases from clear cell renal cell carcinoma and pancreatic neuroendocrine tumor using double-echo chemical shift imaging.

PURPOSE: The purpose of the study was to retrospectively analyze whether double-echo gradient-echo (GRE) chemical shift imaging (CSI) can differentiate between pancreatic metastases from clear cell renal cell carcinoma (PM-ccRCC) and pancreatic neuroendocrine tumor (pNET). METHODS: Institutional review board approval and informed consent were waived. CSI, T2WI, DWI, and DCE magnetic resonance imaging (MRI) were performed in patients with PM-ccRCC and pNET. Eleven patients with PM-ccRCC and 24 patients with pNET were enrolled into this retrospective study. The signal intensity was measured in the pancreatic tumor and spleen on in-phase and opposed-phase images. The signal intensity index (SII) and tumor-to-spleen ratio (TSR) in PM-ccRCC and pNET were calculated and compared. Receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic accuracy of SII and TSR in the differentiation between PM-ccRCC and pNET. RESULTS: The SII between PM-ccRCC and pNET (20.3% ± 16.8% vs. - 3.2% ± 11.4%) was significantly different (P < 0.001), as was the TSR (- 19.2% ± 16.6% vs. 6.0% ± 13.8%) (P < 0.001). The area under the ROC curve was 0.917 for the SII and 0.902 for the TSR. Additionally, an SII threshold value of 8.1% permitted the differentiation of PM-ccRCC from pNET with a sensitivity of 90.9%, a specificity of 91.7%, a positive predictive value of 90.1%, a negative predictive value of 91.7%, and an accuracy of 91.4%. A TSR cut-off value of - 4.7% enabled the differentiation of the two groups with a sensitivity of 79.2%, a specificity of 90.9%, a positive predictive value of 90.9%, a negative predictive value of 79.2% and an accuracy of 82.9%. CONCLUSION: Double-echo GRE chemical shift MR imaging can accurately differentiate between PM-ccRCC and pNET.

Heme oxygenase-1 protects rat liver against warm ischemia/reperfusion injury via TLR2/TLR4-triggered signaling pathways.

AIM: To investigate the efficacy and molecular mechanisms of induced heme oxygenase (HO)-1 in protecting liver from warm ischemia/reperfusion (I/R) injury. METHODS: Partial warm ischemia was produced in the left and middle hepatic lobes of SD rats for 75 min, followed by 6 h of reperfusion. Rats were treated with saline, cobalt protoporphyrin (CoPP) or zinc protoporphyrin (ZnPP) at 24 h prior to the ischemia insult. Blood and samples of ischemic lobes subjected to ischemia were collected at 6 h after reperfusion. Serum transaminases level, plasma lactate dehydrogenase and myeloperoxidase activity in liver were measured. Liver histological injury and inflammatory cell infiltration were evaluated by tissue section and liver immunohistochemical analysis. We used quantitative reverse transcription polymerase chain reaction to analyze liver expression of inflammatory cytokines and chemokines. The cell lysates were subjected to immunoprecipitation with anti-Toll-IL-1R-containing adaptor inducing interferon-ß (TRIF) and anti-myeloid differentiation factor 88 (MyD88), and then the immunoprecipitates were analyzed by SDS-PAGE and immunoblotted with the indicated antibodies. RESULTS: HO-1 protected livers from I/R injury, as evidenced by diminished liver enzymes and well-preserved tissue architecture. In comparison with ZnPP livers 6 h after surgery, CoPP treatment livers showed a significant increase inflammatory cell infiltration of lymphocytes, plasma cells, neutrophils and macrophages. The Toll-like receptor (TLR)-4 and TANK binding kinase 1 protein levels of rats treated with CoPP significantly reduced in TRIF-immunoprecipitated complex, as compared with ZnPP treatment. In addition, pretreatment with CoPP reduced the expression levels of TLR2, TLR4, IL-1R-associated kinase (IRAK)-1 and tumor necrosis factor receptor-associated factor 6 in MyD88-immunoprecipitated complex. The inflammatory cytokines and chemokines mRNA expression rapidly decreased in CoPP-pretreated liver, compared with the ZnPP-treated group. However, the expression of negative regulators Toll-interacting protein, suppressor of cytokine signaling-1, IRAK-M and Src homology 2 domain-containing inositol-5-phosphatase-1 in CoPP treatment rats were markedly up-regulated as compared with ZnPP-treated rats. CONCLUSION: HO-1 protects liver against I/R injury by inhibiting TLR2/TLR4-triggered MyD88- and TRIF-dependent signaling pathways and increasing expression of negative regulators of TLR signaling in rats.

Diagnosis and comprehensive treatment of esophageal leiomyoma: clinical analysis of 77 patients.

To investigate the diagnosis and comprehensive treatment of esophageal leiomyoma. The clinical data of 77 cases of esophageal leiomyoma patients were analyzed between 2005 and 2013. Its diagnosis, treatment and prognosis were analyzed. 39 cases of patients were with eating choking feeling, 18 cases presented with chest pain and weight loss and 20 cases without any symptoms. Preoperative endoscopic ultrasonography of each patient was diagnosed as possibility of esophageal submucosal tumor. 3 All patients underwent tumor enucleation, in which tumor electrotomy under gastroscope were done for 2 cases, complete video-assisted thoracoscopic (CVATS) resection of tumor for 24 cases, thoracoscope assisted small incision tumor resection for 29 cases, conventional thoracic tumor resection for 22 cases. The comparison and the difference of complete video-assisted thoracoscopic surgery group and the thoracoscope assisted small incision group for the operation time, bleeding volume, drainage volume, extubation time, hospitalization time and fasting time were not statistically significant (P < 0.05). All the patients recovered well and postoperative pathology of each patient was esophageal leiomyoma. They were followed up for 6 months to 8 years, average for 4 years, not recurrence of esophageal leiomyoma. Endoscopic ultrasonography is the most accurate method in diagnosis of esophageal leiomyoma. Esophageal leiomyoma which less than 1.0 cm in diameter, regular shape, originated in the muscularis mucosa, endoscopic electrotomy can be used as the preferred; Surgical operation is the main treatment of esophageal leiomyoma, three kinds of operation way has its own corresponding clinical indications, according to the clinical characteristics of patients and operator' habits to choose the corresponding operation way, all can achieve good treatment effect.

Features of gastric glomus tumor: a clinicopathologic, immunohistochemical and molecular retrospective study.

Glomus tumor (GT) of the stomach is a rare mesenchymal tumor. There have been few detailed studies on these tumors. A total of 1894 cases of resected gastric mesenchymal tumors were collected and eleven confirmed gastric GTs were studied. The clinical, pathological, immunohistochemical, ultrastructural and molecular characteristics of the tumors were analyzed through a retrospective study. Histologically, most tumors had gastric smooth muscle immediately adjacent and surrounding the tumor. Tumor cells around blood vessels were small, uniform, and round. Foci of hyaline and myxoid changes were observed. Prominent clear cell features were observed in two tumors. Positive expression of α-smooth muscle actin (α-SMA), laminin, collagen type IV, and vimentin was detected by immunohistochemical analysis in all patients. However, in clear cell areas the expression of α-SMA, laminin, and type IV collagen were mild, while Syn was positive. Moreover, myofibrils and neuroendocrine granules were also present in the cytoplasm of these cells. No C-kit or PDGFR-α genetic mutations were detected in all patients. To conclude, Our results show that GTs in the stomach are histologically and immunophenotypically fully comparable with the glomus tumors of peripheral soft tissues. Neuroendocrine granules and neuroendocrine differentiation were identified in some of the gastric GT cells. Thus, a novel subtype of gastric glomus tumor expressing neuroendocrine cell markers may exist.

Transcription factor ERG is a specific and sensitive diagnostic marker for hepatic angiosarcoma.

AIM: To investigate the expression of ERG, CD34, CD31 (PECAM-1, platelet/endothelial cell adhesion molecule 1) and factor VIII-related antigen (FVIIIRAg) in the diagnosis of hepatic angiosarcoma patients. METHODS: Patient samples were collected from January 1986 to December 2012 from the People's Liberation Army General Hospital in Beijing, China. We obtained twenty-four samples of hepatic angiosarcoma (HAS) that were confirmed by two pathologist. The samples were the result of three autopsy cases, eight biopsy cases and 13 patients who underwent surgical tumor removal. The HAS cases accounted for 2.23% (24/1075) of all hepatic vascular tumors at the hospital during the same time period. Patient histories including age, gender, clinical manifestations, medical treatments, laboratory tests, radiological images, histological observations and outcomes for each case were analyzed in detail. All samples were evaluated histologically with hematoxylin and eosin staining. Using immunohistochemistry, the expression and localization of ERG was examined in all HAS specimens and compared to the known endothelial markers CD34, CD31 and FVIIIRAg. The endothelial markers were also evaluated in a panel of non-HAS tumors. RESULTS: This cohort of 24 HAS cases is, to the best of our knowledge, currently the largest cohort in the world in the publicly available literature. Hepatic angiosarcoma tissue samples were obtained from 14 males and 10 females with a mean age of 50.6 years (range: 7-86 years). The patients presented with the following clinical manifestations: abdominal pain (16/24), back pain (3/24), heart palpitations (1/20), cough (1/24) or no clinical symptoms (3/24). Tumors were predominantly localized in the right hepatic lobe (15/24) or left hepatic lobe (6/24), or a diffuse growth on the right and left hepatic lobes (3/24). Eleven patients underwent surgical resection (45.8%), two patients received a liver transplant (8.3%), eight patients received interventional therapy (33.3%) and three patients received no treatment (lesions discovered at autopsy, 12.5%). Postoperative follow-up of patients revealed that 87.5% (21/24) of patients had died and three cases were not able to be tracked. In all cases, the mean survival time was 12.1 mo. While 100% of the HAS samples were positive for ERG expression, expression of the other markers was more variable. CD31 was expressed in 79.2% (19/24) of samples, CD34 was expressed in 87.5% (21/24) of samples and FVIIIRAg was expressed in 41.7% (10/24) of samples. CONCLUSION: ERG is a more sensitive and specific diagnostic marker for hepatic angiosarcoma in comparison to CD31, CD34 and FVIIIRAg.

Diagnosis and multi-modality treatment of adult pulmonary plastoma: Analysis of 18 cases and review of literature.

The clinical data of 18 patients with PB from April 1989 to April 2013 was analyzed retrospectively, including 11 men and 7 women, aged 45 and 76 years old (mean 53 years). There were 12 cases of PB occurring in right lung and other cases in left lung. Among them, 3 patients had no symptoms, and 15 patients displayed symptoms of cough, chest pain, asthenia or minor haemoptysis. Overall, 11 patients had a preoperative diagnosis of lung cancer, 7 patients were preoperatively diagnosed as the other diseases, which included lung benign tumor (n=5) and mediastinal mass (n=2). All patients received a radical resection. Six patients received postoperative cisplatin-based chemotherapy, and two patients received postoperative irradiation with the dose of 55 Gy. Histologically, 14 cases of 18 patients had biphasic pulmonary blastoma and four cases had well differentiated fetal adenocarcinoma. A total of 12 patients died in a period of 6-36 months after operation, and 1 case was lost after 2 years of follow up. The median survival time was 19 months. PB is a rare primary lung malignant embryonal neoplasm. Despite its assumed embyonal origin, the tumor has a predilection for adults. A preoperative correct diagnosis is very difficult in spite of modern diagnostic imaging and biopsy techniques. Surgical resection is the main method for diagnosis and treatment. Postoperative chemotherapy or irradiation can help eliminate tumor remnants. Its prognosis is very poor, especially for the biphasic type.

[Primary hepatic angiosarcoma: a clinical and pathological analysis].

OBJECTIVE: To investigate the clinicopathological characteristics, differential diagnosis, and prognosis of primary hepatic angiosarcoma, and to review the literature. METHODS: Twenty cases of primary hepatic angiosarcoma were analyzed by gross examination and light microscopy. Immunostaining was performed to detect the expression of CD34, CD31, FVIIIRAg, CK, GPC-3, Hepatocyte,vimentin, PTEN, desmin, and CD117. RESULTS: The age of the patients ranged from 7 to 86 years. Eleven cases were male, and 9 were female. All cases showed no specific clinical manifestations and imaging results. Macroscopically, the tumors showed diffuse multi-nodular or single nodular patterns with hemorrhage. Microscopically, there were various patterns such as cavernous vascular space and epithelioid hemangioendothelioma-like appearances; however, specific pathological diagnostic features of angiosarcoma still existed in all cases. All of the cases expressed at least one of the three immunohistochemical markers: CD31, CD34 and/or FVIIIRag. Ten cases had PTEN low expression. Ki-67 proliferative index was more than 10% in all cases. None of cases expressed desmin, CD117, GPC-3 or Hepatocyte. CONCLUSIONS: Primary hepatic angiosarcoma is a rare malignant tumor. Detailed morphological observation and using various vascular endothelial immunohistochemical markers can help to establish the diagnosis accurately.

[Clinical and pathologic features of gastric schwannoma].

OBJECTIVE: To study the clinical and pathologic features of gastric schwannomas. METHODS: The macroscopic and microscopic features of 9 cases of gastric schwannoma were analyzed. Immunohistochemical study for S-100 protein, CD117, CD34, neurofilament, desmin, nestin, glial fibrillary acidic protein, platelet derived growth factor-alpha (PDGFR-α) and vimentin was carried out. Mutation analysis of c-kit gene (exon 9, 11, 13 and 17) and PDGFR-α gene (exon 12 and 18) in 1 case was examined by PCR amplification and direct sequencing. RESULTS: The patients included 5 males and 4 females. The age of patients ranged from 42 to 81 years (median = 56.5 years). The size of the tumors ranged from 2 to 9 cm in greatest diameter. Follow-up data in 8 cases (from 1 month to 65 months) showed no evidence of recurrence or metastasis. Gross examination showed that gastric schwannomas were homogeneous, firm, yellow-white and bore no true fibrous capsule. Histologically, all cases were composed of fascicles of spindle cells associated with nuclear palisading, Verocay body formation and peripheral cuff of reactive lymphoid aggregates. Some of them showed degenerative changes including cyst formation, calcification, hemorrhage, necrosis and hyalinization. Immunohistochemical study showed that the tumor cells were strongly positive for S-100 protein and vimentin. There was various degree of staining for nestin (8/9) and glial fibrillary acidic protein (6/9). They were negative for CD117, CD34, neurofilament, desmin and smooth muscle actin. One case showed focal positivity for PDGFR-α (1/9), with no mutations found. CONCLUSIONS: Gastric schwannomas share similar histologic features with conventional soft tissue schwannomas, in addition to the presence a reactive lymphoid cuff. The clinical, macroscopic, histologic and immunohistochemical features of gastric schwannomas were different from those of gastrointestinal stromal tumors and leiomyomas.

[Oblique-sagittal black-blood contrast-enhanced magnetic resonance imaging in preoperative evaluation for carotid endarterectomy].

OBJECTIVE: To evaluate the value of oblique-sagittal black-blood contrast-enhanced magnetic resonance imaging (OB-CEMRI) in atherosclerotic carotid artery (CA) assessment before carotid endarterectomy (CEA). METHODS: Twenty-five patients with symptomatic atherosclerotic stenosis in the carotid artery (involving 26 arteries) were scheduled for CEA. OB-CEMRI and digital subtraction angiography (DSA) were conducted within 1 week prior to CEA, and two radiologists independently assessed the location of maximal lumen stenosis, plaque rupture, degree of maximal lumen stenosis and plaque involvement on DSA and OB-CEMRI images. The differences of DSA and the OB-CEMRI in analyzing the plaque conditions were assessed in comparison with matched histological sections of the excised specimens. RESULTS: Compared with the corresponding histological specimens, both DSA (κ=0.807) and OB-CEMRI (κ=0.812) showed a good consistency in defining the location of the maximal lumen stenosis. OB-CEMRI showed a better performance in detecting plaque rupture with higher sensitivity (90.0%) and specificity (83.3%) than DSA (40.0% and 66.7%, respectively). No significant difference was found between DSA and the OB-CEMRI in evaluating the degree of maximal lumen stenosis [(77.33∓3.79)% vs (76.02∓3.95)%, P=0.648]. Compared with the histological examination, OB-CEMRI appeared to underestimate the stenosis. The plaque extent on OB-CEMRI was larger than that on DSA (18.96∓4.96 mm vs 14.80∓3.78 mm, P=0.004), and similar to that by histological examination (18.13∓4.57 mm, P=0.506). CONCLUSIONS: OB-CEMRI allows noninvasive and objective detection of the location of the maximal lumen stenosis, plaque rupture, and plaque extent, though with a lower accuracy than DSA in the assessment of the maximal lumen stenosis. OB-CEMRI combined with DSA offers a more reliable means for preoperative evaluation of the carotid artery plaques for CEA.

[Metastatic alveolar soft tissue sarcoma of the central nervous system: a clinicopathological analysis of four cases].

BACKGROUND AND OBJECTIVE: Metastatic alveolar soft tissue sarcoma (ASTS) of the central nervous system is rare and is easy to be misdiagnosed as other primary tumors of central nervous system. This study was to analyze the clinical and pathological features of four patients with ASTS of the central nervous system and to clarify their differential diagnosis as well as prognosis. METHODS: HE slices and clinical data of the four cases were reviewed and immunohistochemical staining was performed. Antibodies included Vimentin, Myosin, Myoglobin, S-100, Actin, Desmin, CgA, Syn, NSE, and CK. RESULTS: All four patients had a skin nodule of the extremities removed previously. Clinical symptoms included headache and sight blurring. The metastatic lesions were located in the posterior cranial fossa, closely associated with the meninges. The tumor cells had clear or eosinophilic cytoplasm and prominent nucleoli, arranged in alveolar structures, which were surrounded by delicate blood sinuses. The immunohistochemical staining results showed that the positive stainings of Actin, Desmin and S-100 were in 2 cases; the weakly positive stainings of NSE and Vimentin were in 1 case; the positive staining of PAS was in all four cases. The follow-up data showed that one case died during one year after surgery, two cases died during three years. The fourth case had half year after operation and had been alive without tumour. CONCLUSION: ASTS of the central nervous system was mostly metastatic and should be differentiated from other CNS tumors such as meningioma, melonocytic tumor, rhabdomyosarcoma and paraganglioma. Metastatic ASTS of the central nervous system had poor prognosis and the five-year survival rate was low.

[Comparative study on molecular staging of lymph nodes in non-small cell lung cancer patients].

BACKGROUND AND OBJECTIVE: The postoperative survival of patients with non-small cell lung cancer (NSCLC) is mainly determined by clinical pathologic stage. However, recurrence is not rare in stage I NSCLC patients. This study was to explore whether conventional pathologic stages of some NSCLC were underestimated. METHODS: A total of 195 lymph nodes were taken from 25 NSCLC patients during operation. Each lymph node was cut into two parts equally: one part was subjected to hematoxylin-eosin (HE) and immunohistochemical (IHC) staining; the other part of the lymph nodes in the same region in a given patient was mixed for reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: With HE staining, 30 of the 195 lymph nodes showed gross nodal metastasis, and none showed micrometastasis. IHC staining was performed on 135 lymph nodes that were identified as free of metastasis by HE staining, 31 showed micrometastasis; none showed gross nodal metastasis. Of 39 groups of mixed regional lymph nodes which were diagnosed to be free of metastasis by HE staining, 11 groups were found to be positive by RT-PCR. There was a correlation between IHC staining and RT-PCR for detection of nodal micrometastasis of NSCLC (U=7.682, P<0.001). CONCLUSIONS: HE staining can accurately detect gross nodal metastasis in NSCLC patients, but is unfit for detecting nodal micrometastasis. IHC staining can improve the detection rate of occult nodal micrometastasis. RT-PCR has similar value to IHC staining in detecting nodal micrometastasis.

[Comparative study for detecting micrometastases of lymph nodes in patients with lung cancer].

OBJECTIVE: To set up a new method to detect occult micrometastases of lymph nodes in patients with no-small-cell lung cancer (NSCLC). METHODS: We had detected 195 lymph node samples taken from 25 patients with NSCLC during the operations. Each lymph node sample was divided into two same parts in size. The one half part of lymph node should be examined by conventional histopathologic examination and immunohistochemical (IHC) staining. All the remaining lymph node samples of each patient should be mixed together for the reverse transcriptase-polymerase chain reaction (RT-PCR) if they located in the same region. As long as the presence of metastatic tumor in one lymph node was found by H&E staining, all other lymph node samples in the same region should not be detected by IHC staining or RT-PCR techniques. RESULTS: Frozen tissue sections of 135 lymph nodes that were staged as free of metastases by conventional histopathologic examination were screened by IHC staining. 31 lymph nodes showed single cell or cells clusters. Of 39 groups mixed regional lymph nodes which were diagnosed to be devoid of metastases by conventional histopathologic examination, 11 groups were found to have positive reactions to cytokeratin 19-mRNA by RT-PCR. There was a correlation between IHC staining and RT-PCR for detection of nodal micrometastases of NSCLC (U = 7.682, P = 0.0001). CONCLUSION: IHC staining analysis can facilitate the detection of occult micrometastases in lymph nodes of NSCLC, and its assessment of nodal micrometastases can provide a refinement of TNM stage for partial patients with stage I to II. RT-PCR has the same value as IHC staining in detection of lymph nodal micrometastases. RT-PCR technique can reduce expense of the detecting micrometastases in lymph nodes.

[Clinicopathological study on nodal molecular staging of non-small-cell lung cancer].

OBJECTIVE: To investigate the practicability of detecting the micrometastasis in lymph nodes of no-small-cell lung cancer (NSCLC) by means of reverse transcriptase-polymerase chain reaction (RT-PCR). METHODS: Regional lymph node samples were collected during operation from 25 patients with NSCLC randomly selected. The lymph node sample from each patient was divided into 2 groups: lymph nodes of hilum of lung and of mediastinum. Every lymph node was divided into two parts of the same size. One half part of the lymph node was examined by hematoxylin eosin (H&E) staining. If HE staining discovered metastasis, further examination was not needed. If HE staining failed to discover metastasis, then all the remaining lymph node samples of each patient were mixed together to undergo RT-PCR for cytokeratin 19 (CK(19)), a tissue marker of epithelium and epithelial tumors. RESULTS: (1) 195 lymph nodes from 25 patients with NSCLC were examined by H&E staining. 30 lymph nodes in 9 patients showed gross nodal metastasis and none showed micrometastatic tumor cells. (2) Of the 39 groups of mixed regional lymph node samples which were diagnosed to be devoid of metastases by H&E staining, 11 groups were found to have positive reactions to CK(19) mRNA. (3) Six of the sixteen patients staged as PN(0) had hilum lymph nodal micrometastasis, while 5 of nine patients with stage PN(1) had mediastinal lymph nodal micrometastasis (chi(2) = 54.063, P = 0.0043). CONCLUSION: (1) H&E staining can accurately detect gross nodal metastasis in the lymph nodes of the patients with NSCLC, but is unfit for detecting lymph nodal micrometastasis. (2) RT-PCR can facilitate the detection of occult micrometastatic tumor cells in the lymph nodes of NSCLC, and its assessment of nodal micrometastasis can provide a refinement of molecular stage for partial patients with stage I to II.

[Clinical pathological study on nodal micrometastases of non-small-cell lung cancer].

OBJECTIVE: To investigate the practicability of detecting the micrometastases in lymph nodes of no-small-cell lung cancer (NSCLC) by means of the immunohistochemical (IHC) staining. METHODS: The lymph node samples were taken from the patients with NSCLC during the operations. Firstly, each resulting tissue block was processed for routine paraffin embedding. Then the 6 approximately 10 serial sections were chosen, each 5 microm thick, from every paraffin block of the lymph node. Finally, the first and the second last sections of each lymph node were stained by hematoxylin eosin (HE), and the other serial sections were used for the IHC staining examination with the monoclonal antibody against cytokeratin 19. RESULTS: The paraffin embedded sections of 195 regional lymph nodes from 25 patients with NSCLC were examined by HE staining. Thirty lymph nodes in 9 patients revealed gross nodal metastases, and none of lymph node in 25 patients showed micrometastatic tumor cells. Frozen tissue sections from 135 regional lymph nodes that were staged as free of metastases by HE staining were screened by IHC staining. Thirty-one lymph nodes in 9 patients showed micrometastatic tumor cells. Five of sixteen patients staged as PN(0) had hilum lymph nodal micrometastases, versus four of nine patients with stage PN(1) had mediastinal lymph nodal micrometastases. There was a significant difference between two groups (chi(2)=52.900, P=0.0193). CONCLUSIONS: Conventional HE staining can accurately detect gross nodal metastases in the lymph nodes of patients with NSCLC, but is unfit for detecting lymph nodal micrometastases. IHC staining analysis can significantly facilitate the detection of occult micrometastatic tumor cells in lymph nodes of NSCLC, and its assessment of nodal micrometastases can provide a refinement of TNM stage for partial patients with stage I to II NSCLC.

[Expression of the genes FHIT, Bcl-2 and Bax in breast infiltrating ductal carcinoma and clinicopathological significance thereof].

OBJECTIVE: To investigate the expression of the genes fragile histidine triad (FHIT), Bcl-2, and Bax, biological markers of breast infiltrating ductal carcinoma in this carcinoma and clinicopathological significance thereof. METHODS: The clinical data of 100 patients with breast infiltrating ductal carcinoma, all females, aged 435 (28 - 92), were collected. Immunohistochemistry was used to detect the protein expression of FHIT, Bcl-2 and Bax in the carcinoma tissues resected during operation. RESULTS: The protein expression rates of FHIT, Bcl-2 and Bax in the tumor tissues were 73%, 50%, and 34% respectively. The disease free survival (DFS) and overall survival (OS) of the FHIT positive patients were 81.8 months and 123.6 months, both significantly longer than those of the FHIT-negative patients (27.7 months and 74 months, both P < 0.05). The DFS of the Bcl-2-positive patients was 83 months, significantly longer than that of the Bcl-2-negative patients (45 months, P < 0.05). The mean DFS of the Bcl-2-positive patients who received postoperative adjuvant chemotherapy was 54.8 months, significantly longer than that of the Bcl-2-negative patients who received postoperative adjuvant chemotherapy (41.6 months). The mean DFS and OS of the Bcl-2-negative patients receiving CAF regimen were 55 months and 58.8 months respectively, both longer than those of the Bcl-2-negative patients receiving other regimens (27 months and 36 months respectively). However, the expression of Bax failed to show correlation with the prognosis of breast infiltrating ductal carcinoma. CONCLUSION: Expression of FHIT and expression of Bcl-2 are positively correlated to the DFS and OS of the breast infiltrating ductal carcinoma. Bax is not predictive to the prognosis of breast infiltrating ductal carcinoma.