molecular pathology of intraductal papillary mucinous neoplasms of the pancreas

Since the first description of intraductal papillary mucinous neoplasms(IPMNs)of the pancreas in the eighties,their identification has dramatically increased in the last decades,hand to hand with the improvements in diagnostic imaging and sampling techniques for the study of pancreatic diseases.However,the heterogeneity of IPMNs and their malignant potential make difficult the management of these lesions.The objective of this review is to identify the molecular characteristics of IPMNs in order to recognize potential markers for the discrimination of more aggressive IPMNs requiring surgical resection from benign IPMNs that could be observed.We briefly summarize recent research findings on the genetics and epigenetics of intraductal papillary mucinous neoplasms,identifying some genes,molecular mechanisms and cellular signaling pathways correlated to the pathogenesis of IPMNs and their progression to malignancy.The knowledge of molecular biology of IPMNs has impressively developed over the last few years.A great amount of genes functioning as oncogenes or tumor suppressor genes have been identified,in pancreatic juice or in blood or in the samples from the pancreatic resections,but further researches are required to use these informations for clinical intent,in order to better define the natural history of these diseases and to improve their management.

European vs 2015-World Health Organization clinical molecular and pathological classification of myeloproliferative neoplasms

The BCR/ABL fusion gene or the Ph^1-chromosome in the t(9;22)(q34;q11)exerts a high tyrokinase acticity,which is the cause of chronic myeloid leukemia(CML).The1990 Hannover Bone Marrow Classification separated CML from the myeloproliferative disorders essential thrombocythemia(ET),polycythemia vera(PV)and chronic megakaryocytic granulocytic myeloproliferation(CMGM).The 2006-2008 European Clinical Molecular and Pathological(ECMP)criteria discovered 3variants of thrombocythemia:ET with features of PV(prodromal PV),"true"ET and ET associated with CMGM.The 2008 World Health Organization(WHO)-ECMP and 2014 WHO-CMP classifications defined three phenotypes of JAK2^(V617F)mutated ET:normocellular ET(WHO-ET),hypercelluar ET due to increased erythropoiesis(prodromal PV)and ET with hypercellular megakaryocytic-granulocytic myeloproliferation.The JAK2^(V617F)mutation load in heterozygous WHO-ET is low and associated with normal life expectance.The hetero/homozygous JAK2^(V617F)mutation load in PV and myelofibrosis is related to myeloproliferative neoplasm(MPN)disease burden in terms of symptomaticsplenomegaly,constitutional symptoms,bone marrow hypercellularity and myelofibrosis.JAK2 exon 12mutated MPN presents as idiopathic eryhrocythemia and early stage PV.According to 2014 WHO-CMP criteria JAK2 wild type MPL^(515)mutated ET is the second distinct thrombocythemia featured by clustered giant megakaryocytes with hyperlobulated stag-horn-like nuclei,in a normocellular bone marrow consistent with the diagnosis of"true"ET.JAK2/MPL wild type,calreticulin mutated hypercellular ET appears to be the third distinct thrombocythemia characterized by clustered larged immature dysmorphic megakaryocytes and bulky(bulbous)hyperchromatic nuclei consistent with CMGM or primary megakaryocytic granulocytic myeloproliferation.

PVSG and WHO vs European Clinical,Molecular and Pathological Criteria for prefibrotic myeloproliferative neoplasms

The Polycythemia Vera Study Group(PVSG),World Health Organization(WHO) and European Clinical,Molecular and Pathological(ECMP) classifications agree upon the diagnostic criteria for polycythemia vera(PV) and advanced primary myelofibrosis(MF). Essential thrombocythemia(ET) according to PVSG and 2007/2008 WHO criteria comprises three variants of JAK2V617 F mutated ET when the ECMP criteria are applied. These include normocellular ET,hypercellular ET with features of early PV(prodromal PV),and hypercellular ET due to megakaryocytic,granulocytic myeloprolifera-tion(ET.MGM). Evolution of prodromal PV into overt PV is common. Development of MF is rare in normocellular ET(WHO-ET) but rather common in hypercellular ET.MGM. The JAK2V617 F mutation burden in heterozygous mutated normocellular ET and in heterozygous/homozygous or homozygous mutated PV and ET.MGM is of major prognostic significance. JAK2/MPL wild type ET associated with prefibrotic primary megakaryocytic and granulocytic myeloproliferation(PMGM) is characterized by densely clustered immature dysmorphic megakaryocytes with bulky(bulbous) hyperchromatic nuclei,which are never seen in JAK2V617 F mutated ET,and PV and also not in MPL515 mutated normocellular ET(WHO-ET). JAK2V617 mutation burden,spleen size,LDH,circulating CD34+ cells,and pre-treatment bone marrow histopathology are mandatory to stage the myeloproliferative neoplasms ET,PV,PMGM for proper prognosis assessment and therapeutic implications. MF itself is not a disease because reticulin fibrosis and reticulin/collagen fibrosis are secondary responses of activated polyclonal fibroblasts to cytokines released from the clonal myeloproliferative granulocytic and megakaryocytic progenitor cells in ET.MGM,PV and PMGM.

Cavitary Pulmonary Metastases: CT Features and Their Correlation with the Pathology of the Primary Malignancy

Objective: To study CT features of cavitary pulmonary metastases and to investigate the pos- sible relationship between CT features and the pathology of the primary lesions. Methods: CT ?ndings of 131 cavitary metastatic nodules in 40 patients with pathologically-proved pulmonary metastases were retrospectively analyzed. A comparison between CT signs and the pathologic types of the primary tumors was made. Results: Cavitary metastases and multiple solid nodules coexisted in all patients. Cavitary metastases presented as bubble (n=41), irregular (n=33), cystic (n=26) or small circular (n=31) cavities, with even (n=61) or uneven (n=70) thickness of the cavity wall. Of 131 cavitary nodules, diameter less than 15 mm was seen in 44, between 15–25 mm in 66, 25–40 mm in 17 and larger than 40 mm in 4 respectively. And the wall thickness of the cavity below 4 mm, between 4–15 mm and over 15 mm was respectively seen in 69, 44 and 18 metastatic nodules. Cavitary pulmonary metastases mainly occurred in patients whose primary malignancy was squamous cell carcinoma (n=13) or adenocarcinoma (n=22). Both squamous cell carcinoma and adenocarcinoma had its own CT characteristics. The occurrence of cavity bore no relationship to its site in the lung. Conclusion: Cavitary pulmonary metastases carries certain CT features and its occurrence is related to the pathologic type of the primary malignancy.

Intraductal papillary-mucinous neoplasia of the pancreas:Histopathology and molecular biology

Intraductal papillary-mucinous neoplasm(IPMN) of the pancreas is a clinically and morphologically distinctive precursor lesion of pancreatic cancer,characterized by gradual progression through a sequence of neoplastic changes.Based on the nature of the constituting neoplastic epithelium,degree of dysplasia and location within the pancreatic duct system,IPMNs are divided in several types which differ in their biological properties and clinical outcome.Molecular analysis and recent animal studies suggest that IPMNs develop in the context of a field-defect and reveal their possible relationship with other neoplastic precursor lesions of pancreatic cancer.

A clinicopathological analysis in unsuspected gallbladder carcinoma: A report of 23 cases

AIM： To study the clinicopathological characteristics of unsuspected gallbladder carcinoma （UGC）. METHODS： We retrospectively studied 23 cases of UGC in Tongji Hospital, and compared their clinicopathological characteristics with 33 cases of preoperatively diagnosed gallbladder carcinoma （PDGC）. RESULTS： The proportion of UGC coexisting with cholecystolithiasis was significantly higher than that of PDGC （x^2 = 13.53, P 〈 0.01）. The infection rate of hepatitis B virus was 21.74% （5/23） in UGC and 30.30% （10/33） in PDGC. Nine （39.13%） of 23 patients with UGC and 8/33 （24.24） PDGC had contact with schistosome pestilent water. The rate of multiple pregnancies was 56.52% （13/23） in the patients with UGC and 42.42% （14/33） in PDGC. The primary location of the UGC was mostly in the neck and body of the gallbladder, and that of the PDGC was often in the body and bottom. The incidence of Nevin stage I and 11 UGC was significantly higher than that of PDGC （x^2 = 4.44, P 〈 0.05 and 2 = 4.96, P 〈 0.05） while that of Nevin stage V UGC was significantly lower than that of PDGC （x^2 = 7.59, P 〈 0.01）. According to the grading of carcinoma, the incidence of well-differentiated UGC was significantly higher than that of PDGC （2 = 4.16, P 〈 0.05）, and that of poorlydifferentiated UGC was significantly lower than that of PDGC （x^2 = 4.48, P 〈 0.05）.CONCLUSION： There are different characteristics between UGC and PDGC, such as in primary location, malignant degree and incidence of coexistence with cholecystolithiasis. Cholecystolithiasis, hepatitis B, schistosome and multiple pregnancies were high risk factors for gallbladder carcinoma.

Plasmacytoid Transitional Cell Carcinoma of Bladder： A Clinico-pathological Study and Review of Literatures

Objective： To study the pathologic features of plasmacytoid transitional cell carcinoma of the bladder, and to analyze the diagnostic features, criteria for differential diagnosis and the clinical significance of the tumor. Methods： Two cases of bladder plasmacytoid transitional cell carcinoma were studied. Routine paraffin sections with HE staining, Pap smear and immunohistochemistry by S-P method were observed under a light microscope. Pathological and clinical data were analyzed by comparison with early reported cases in literatures. Results： A characteristic feature of this tumor was of deep invasion in the lamina propria and/or muscularis propria, in addition to the component of carcinoma in situ in the mucosa, when tumors were diagnosed. The histological pattern and cytological features showed similarity to a plasmacytoid tumor. The tumor cells were strongly positive for AE1/AE3, CEA and CK18. The prognosis appeared to be worse than ordinary transitional cell carcinoma. Conclusion： The plasmacytoid transitional cell carcinoma of bladder is rare but has typical pathological, immunohistological and clinical features. Pathologists should be aware of this kind of primary tumor of bladder.

Clinicopathologic Observation of 6 Cases with Neuroendocrine Carcinoma of the Urinary Bladder

OBJECTIVE To discuss the pathologic characteristics and theprognosis of neuroendocrine carcinoma of the bladder(NECB)in order to assist in making a precise diagnosis and to effectivelytreat the disease.METHODS Clinicopathologic features of the 6 cases with NECBwere analyzed retrospectively.The personal data of the patientsand the pathologic and immunohistochemical characteristics ofthe tumor were investigated.The follow-up of these patients wasconducted over a time period ranging from 3 months to 9 years.RESULTS Transurethral resection of the bladder tumorwas performed in all 6 patients.Based on the results of thepathologic examination,4 of the cases were diagnosed as smallcell neuroendocrine carcinoma and the other 2 were diagnosedas atypical carcinoid tumor.On immunohistochemical stainingall tumors expressed neuroendocrine markers includingneuronspecific enolase(CD56),synaptophysin(Syn)andchromogranin(CgA).In patients receiving partial cystectomyfollowed by postoperative chemotherapy,relapse was found in 4of the 6 cases on follow up.CONCLUSION NECB is a rare entity and a tumor with highmalignant potential and characteristic pathologic features.Hematuria is the cardinal symptom of NECB.Metastasis mayoccur at an early stage and the prognosis of the disease is poor.Final diagnosis of NECB depends on histopathologic examinationand immunohistochemical assays.Surgical excision combinedwith radiotherapy and chemotherapy is considered an effectivetreatment.

Clinicopathological Analysis of Patients with Nonmuscle-Invasive Bladder Cancer Who Underwent Radical Cystectomy

Objectives: Surgical specimens obtained at the time of the last transurethral resection of bladder tumor (TURBT) for patients with nonmuscle-invasive bladder cancer (NMIBC) who underwent radical cystectomy were retrospectively evaluated in order to investigate the relationship between pathological variation and upstaging of NMIBC. Methods and Materials: Twenty patients (19 men, 1 woman;aged 69.4 ± 12.1 (mean ± SD) years) diagnosed with NMIBC underwent radical cystectomy during follow-up. Results: Five of the 20 patients (25%) had pathological upstaging in the radical cystectomy specimens. There was a statistical association between pathological upstaging and cancer death (p = 0.002). There were three patterns of pathological variation in the upstaged specimens: 1) in patients with BCG-resistant NMIBC, urothelial carcinoma invaded through the lamina propria;2) urothelial carcinoma showed diffuse invasion beyond the deep lamina propria, and the cancer cells had infiltrated as single cells and formed nodules;3) TURBT specimens showed a micropapillary variant. Conclusions: Since these pathological variations correlated with pathological upstaging, they may provide an indication for cystectomy in NMIBC patients.

The accuracy of magnetic resonance imaging and ultrasound in evaluating the size of early-stage breast neoplasms

Objective Breast cancer is the most frequently diagnosed cancer in women. Accurate evaluation of the size and extent of the tumor is crucial in selecting a suitable surgical method for patients with breast cancer. Both overestimation and underestimation have important adverse effects on patient care. This study aimed to evaluate the accuracy of breast magnetic resonance imaging(MRI) and ultrasound(US) examination for measuring the size and extent of early-stage breast neoplasms.Methods The longest diameter of breast tumors in patients with T_(1–2)N_(0–1)M_0 invasive breast cancer preparing for breast-conserving surgery(BCS) was measured preoperatively by using both MRI and US and their accuracy was compared with that of postoperative pathologic examination. If the diameter difference was within 2 mm, it was considered to be consistent with pathologic examination.Results A total of 36 patients were imaged using both MRI and US. The mean longest diameter of the tumors on MRI, US, and postoperative pathologic examination was 20.86 mm ± 4.09 mm(range: 11–27 mm), 16.14 mm ± 4.91 mm(range: 6–26 mm), and 18.36 mm ± 3.88 mm(range: 9–24 mm). US examination underestimated the size of the tumor compared to that determined using pathologic examination(t = 3.49, P < 0.01), while MRI overestimated it(t =-6.35, P < 0.01). The linear correlation coefficients between the image measurements and pathologic tumor size were r = 0.826(P < 0.01) for MRI and r = 0.645(P < 0.01) for US. The rate of consistency of MRI and US compared to that with pathologic examination was 88.89% and 80.65%, respectively, and there was no statistically significant difference between them(χ~2 = 0.80, P > 0.05).Conclusion MRI and US are both effective methods to assess the size of breast tumors, and they maintain good consistency with pathologic examination. MRI has a better correlation with pathology. However, we should be careful about the risk of inaccurate size estimation.

Primary large cell neuroendocrine carcinoma of the bladder:A case report

BACKGROUND Large cell neuroendocrine carcinoma(LCNEC)of the bladder is a rare nonurothelial tumor of the bladder.The treatment of LCNEC of the bladder is different from that of urothelial carcinoma(UC);therefore,early and accurate diagnosis is particularly important.As LCNEC of the bladder is rare and its clinical symptoms and radiographic features are similar to those of urothelial tumors,the clinical diagnosis of the disease remains challenging.CASE SUMMARY We report a 72-year-old female patient who presented with gross hematuria for 3 mo.A solitary tumor located in the anterior wall of the bladder was found by cystoscopy.Pathological examination after biopsy suggested UC of the bladder in the absence of immunohistochemical assessment.The patient underwent partial cystectomy and was finally diagnosed with LCNEC(pT2bN0M0)based on the results of postoperative immunohistochemical examination.During the 10-mo follow-up,no signs of tumor recurrence or metastasis were found.CONCLUSION Immunohistochemical examination is essential for diagnosing LCNEC of the bladder.Accurate diagnosis and multidisciplinary treatment in the early stage of the disease are crucial for improving the prognosis.

Blastic plasmacytoid dendritic cell neoplasm in Jinhua,China:Two case reports

BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare and clinically aggressive hematologic malignancy originating from the precursors of plasmacytoid dendritic cells.BPDCN often involves the skin,lymph nodes,and bone marrow,with rapid clinical progression and a poor prognosis.The BPDCN diagnosis is mainly based on the immunophenotype.CASE SUMMARY In this paper,we retrospectively analyzed 2 cases of BPDCN.Both patients were elderly males.The lesions manifested as skin masses.Morphological manifestations included diffuse and dense tumor cell infiltration of the dermis and subcutaneous tissues.Immunohistochemistry staining showed that cluster of differentiation CD4,CD56,CD43,and CD123 were positive.CONCLUSION In this paper,we retrospectively analyzed 2 cases of BPDCN.Both patients were elderly males.The lesions manifested as skin masses.Morphological manifestations included diffuse and dense tumor cell infiltration of the dermis and subcutaneous tissues.Immunohistochemistry staining showed that cluster of differentiation CD4,CD56,CD43,and CD123 were positive.

Clinico-pathologic significance of neuroendocrine cells in gastric carcer tissue

AIMS To elucidate the biological and clinicopathological signifi- cance of neuroendocrine(NE)cells in gastric carcinoma(GC). METHODS One hundred and eighty-nine cases of various histo- logical types of GC were observed using light microscopy, histochemistry,immunohistochemistry and electron microscopy. Of them 127 patients were followed up. RESULTS Chromogranin A(CgA)positive GC was demonstrat- ed in 85 cases(45.0%).The typos of NE cells in GC were probed using 9 kinds of hormone antibodies 49 cases(67.2%) contained more than one hormone.NE cells were found more often in poorly differentiated GC than in well differentiated ones(P<0. 01).Expression of some kinds of hormone Was relative to the dif- ferentiation and histological types of GC.BOM,CT(P<0.01) GAST and 5-HT(P<0.05)were more expressed in poorly differ- entiated cases than in well defferentiated ones.Nineteen cases of the matastatic foci in regional lymph nodes were found to have CgA positive cancer cells.The presence of HCG in matastatic lymph nodes was more often observed than that of other hormone (P<0.01).The survival rate of patients with NE positive GC was 38.9% and negative GC 52.7%.Five of 7 patients(71. 4%)with somatostatin positive GC still survived at follow up of 33-66 months,but 4 patients with HCG positive GC died in 12-29 months. CONCLUSIONS The NE cells occur more frequently in poorly differentiated GC.Certain hormones appear to be related to the metastasis and prognosis.

Histopathological study of hepatocellular carcinoma after transcatheter hepatic arterial embolization

AIMS To study the histopathological changes in hepatocellular carcinoma (HCC) after transcatheter arterial embolization (TAE). METHODS Histopathological analysis was made in 39 cases of liver neoplasms after TAE and 11 cases of liver neoplasms after digital selective angiography (DSA), including pathological type, histological grade, necrotic degree, capsule, times of treatment, injured vessel and lymphocyte infiltration. RESULTS Six cases with 100% necrosis, 14 cases with 30% 95% necrosis, 19 cases with 0% 5% necrosis after TAE and 11 cases without necrosis after DSA were found histologically. The necrosis was related to the pathological type, capsule, injured vessels, but not to the histological grade, time of treatment and lymphocyte infiltration of the liver neoplasms. CONCLUSIONS TAE is an effective therapy for the late stage HCC. The encapsulated HCC is a preferable indicator for TAE.

Infantile hepatic hemangioendothelioma:A clinicopathologic study in a Chinese population

AIM:To investigate whether the clinicopathologic features of infantile hemangioendothelioma(IHE) of the liver in a Chinese population are similar to the features observed in other races.METHODS:The clinical data,radiological findings,histopathological changes and outcome of 12 cases of IHE diagnosed by the Department of Pathology,West China Hospital over the last 10 years were analyzed retrospectively.Immunohistochemical studies were carried out using antibodies against CD31,CD34,Factor Ⅷ,cytokeratin 8 and cytokeratin 18.RESULTS:The 12 patients were aged from fetal to 5 years(three males and nine females).The tumor was presented with different clinical manifestations,mainly as an asymptomatic,palpable,upper abdominal mass,except for the two fetuses who were detected antena-tally by ultrasound.In one patient,this presentation was accompanied by an initial severe pneumothorax.No symptoms of congestive heart failure were present and neither congenital abnormalities nor vascular tumors in the skin or other organs were found.Laboratory abnormalities included leukocytosis(40%),anemia(60%),thrombocytosis(60%),hyperbilirubinemia(16.7%),abnormal liver function(50%) and increased α-fetoprotein(80%).Based on radiological findings and gross specimens,the tumor presented as a solitary lesion or a multifocal space-occupying lesion.The tumor size ranged from 5.0 cm × 3.5 cm × 2.0 cm to 13.8 cm × 9.0 cm × 7.7 cm,and the 0.2-1.1 cm nodules were diffusely distributed within the multifocal tumor.Seven cases were surgically resected,three cases underwent biopsy and the two fetuses were aborted.Histologically,nine cases were classified as typeⅠ and three as type Ⅱ,presenting aggressive morphologic features,immature vessels,active mitosis and necrosis.An inflammatory component,predominantly eosinophilic granulocytes,sometimes obscured the nature of the tumor.Ten patients are alive after a follow-up of 1-9 years.Based on immunohistochemistry,the endothelial cells in all cases were positive for CD31,CD34 and polyclonal factor Ⅷ antigen,whereas the scattered hyperplasia bile ducts were positive for cytokeratin 8 and cytokeratin 18.CONCLUSION:The clinical manifestations of IHE are non-specific.There is no significant correlation between histological type and prognosis.The clinicopathologic features of IHE in Chinese patients may provide a clue to further evidence-based studies.

Basaloid squamous carcinoma of esophagus:a clinicopathological,immunohistochemical and electron microscopic study of sixteen cases

AIM To further clarify the clinicopathological, immunohistochemical and electron microscopic features, and prognostic aspect of basaloid squamous carcinoma (BSC), a rare esophageal carcinoma.METHODS We reviewed 763 documented cases of esophageal malignancies from year (1977-1996) from our hospital, and discovered 16 (2.1%) cases of BSC. The clinicopathological features of these cases were evaluated. Immunohistochemistry (S-P method), histochemical stains, and electron microscopy were used to further characterize the neoplasm.RESULTS The tumors were classified into stages Ⅰ (n=1), ⅡA (n=6), ⅡB (n=2), Ⅲ (n=5), and Ⅳ (n=2) according to the criteria of the UICC TNM classification system of malignant tumors (1987). Most neoplasms were located in the mid third of the esophagus. Grossly, they had a similar appearance of conventional esophageal carcinoma, but showed a typical cytoarchitectural pattern of BSC histologically. The most important histologic feature of this tumor is carcinoma with a basaloid pattern, intimately associated with squamous cell carcinoma, dysplasia, or focal squamous differentiation. The basaloid cells were round to oval in shape with scant cytoplasm, arranged mainly in the form of solid, smooth-contoured lobules with peripheral palisading. A panel of immunostains were used for the basaloid component of the tumor with the following results: CK(Pan) 14/16 (+); EMA 16/16 (+); Vimentin 4/16 (+); S-100 protein 7/16 (+). CEA and smooth muscle actin were negative. Electron microscopy (EM) revealed that the basaloid cells were poorly differentiated, with a few desmosomes and fibrils, and numerous free and polyribosome. Of the 11 patients with adequate follow-up 8 died within 2 years, with an average survival time of 16.2 months. No stage Ⅱ, Ⅲ or Ⅳ cases survived beyond 5 years. The one-year survival rate was 60% and two-year 20%.CONCLUSION The BSC of esophagus is a distinct clinicopathological entity with poor prognosis. The cellular differentiation and biologic behavior of esophageal BSC were assumed to occupy a station intermediate between that of conventional squamous cell carcinoma and small undifferentiated cell carcinoma.

Comparisons of voided urine cytology, nuclear matrix protein-22 and bladder tumor associated antigen tests for bladder cancer of geriatric male patients in Taiwan, China

Aim： To compare the results of bladder tumor associated antigen （BTA TRAK）, nuclear matrix protein 22 （NMP 22） and voided urine cytology （VUC） in detecting bladder cancer. Methods： A total of 135 elderly male and 50 healthy volunteers enrolled in this study were classified into three groups： （i） 93 patients with bladder cancer; （ii） 42 patients with urinary benign conditions; and （iii） 50 healthy volunteers. BTA TRAK and NMP 22 kits were used to detect bladder cancer. Voided urine cytology was used to compare the sensitivity and specificity of the screening tests. Results： The sensitivity and specificity of cytology, BTA TRAK and NMP 22 were 24% and 97%, 51% and 73%, 78% and 73%, respectively. The level of NMP 22 increased with tumor grading. The BTA TRAK kit has the lowest sensitivity among the screening tests. The NMP 22 with the best sensitivity can be an adjunct to cytology for evaluating bladder cancer. Conclusion： The NMP 22 test has a better correlation with the grading of the bladder cancer than BTA TRAK. As cytology units are typically not available in hospitals or in outpatient clinics, NMP 22 might be a promising tool for screening bladder cancer.

Classification of gastric neuroendocrine tumors and its clinicopathologic significance

AIMS To study the pathologic classification of gastric neuroendocrine tumors and its clinicopathologic significance. METHODS Paraffin embedded sections of 52 gastric neuroendocrine tumors including 42 carcinoid tumors, and 10 cases of neuroendocrine carcinoma from 326 patients who underwent resection of stomach carcinomas were studied by immunohistochemical methods including 10 endocrine markers or hormones antibodies and endocrine cells in gastric neuroendocrine tumors and extratumoral mucosa were observed under electromicroscope. RESULTS The 52 gastric neuroendocrine tumors were divided into three types: ① Gastrin dependent type of carcinoid (26 cases) accompanied by chronic atrophic gastritis (CAG) and tumor extension limited to the mucosa or submucosa complicated with hypergastrinemia and G cell hyperplasia. This type was consistently preceded by and associated with generalized proliferation of endocrine cells in the extratomoral fundic mucosa. ② Non gastrin dependent type of carcinoids (16 cases) associated with neither CAG nor hypergastrinemia. This type was more aggressive; and ③ Neuroendocrie carcinomas (10 cases), which are highly aggressive tumors. CONCLUSIONS A correct identification of different types of gastric endocrine tumors has major implications for the treatment and prognosis of the patients.

Relationship between expression of laminin and pathological features in human colorectal carcinoma

AIM To study the expression and significance of laminin in human colorectal carcinoma. METHODS Using the monoclonal antibody to laminin and streptavidin peroxidase immunohistochemical method, the expression of laminin in 63 cases of human colorectal carcinoma tissues was determined. RESULTS In normal large intestinal mucosa adjacent to carcinoma, laminin was largely restricted to basement membrane in continuous linear pattern. In contrast, human colorectal carcinomas exhibited a progressive loss of an intact basement membrane that was correlated with decreasing differentiation degree. Well and moderately differentiated tumors exhibited a thin basement membrane with intermittent disruptions, and poorly differentiated tumors exhibited no areas of intact basement membrane. An association was found between lack of basement membrane laminin immunohistochemical staining in colorectal carcinoma and poorly differentiated tumor ( P <0 01) . CONCLUSION Immunohistochemical staining for laminin could provide a very useful index for the determination of the differentiation degree of colorectal carcinoma.