Clinical Pathological Examination Research Articles

Ultrasonography Misdiagnosis of Postmenopausal Endometrial Tuberculosis(PET) Caseous Necrosis: A Case report

Objective: To reduce misdiagnosis and not misdiagnose of postmenopausal endometrial tuberculosis. Method: Analyzing a case of postmenopausal endometrial tuberculosis caseous necrosis misdiagnosed as endometrial cancer by ultrasonography. Result: This case was clearly diagnosed as postmenopausal endometrial tuberculosis by means of hysteroscopy curettage and pathological examination, thereby the misdiagnosis was rectified. Conclusion: Ultrasonography has significant implications for clinical diagnosis of postmenopausal caseous endometrial tuberculosis and identification of endometrial cancer. It is suggested to carry out clinical curettage and pathological examination in time so as to reduce misdiagnosis of postmenopausal endometrial tuberculosis.

Hyperuricemia is an independent risk factor for renal pathological damage and poor prognosis in lupus nephritis patients.

To explore the correlation between hyperuricemia and renal damage in patients with lupus nephritis (LN). Methods: The data for clinical features, laboratory and renal pathological examination were collected from 177 renal biopsy-proven LN patients with or without hyperuricemia and were retrospectively analyzed to determine the correlation between serum uric acid and renal damage. Results: LN patients with hyperuricemia group had higher rate of hypertension and higher level of blood urea nitrogen and serum creatinine while lower estimated glomerular filtration rate (eGFR) and lower positive rate of anti-U1RNP antibody (P<0.05). In the LN patients with hyperuricemia group, renal pathological scores, including acitive index, chronic index and tubulointerstitial lesions, were higher than those in the LN patients without hyperuricemia group (P<0.05). The level of serum uric acid was positively correlated with serum creatinine, renal pathological classification and renal pathological scores while negatively correlated with eGFR (P<0.05). Conclusion: LN patients with hyperuricemia are associated with more serious renal damage. Hyperuricemia is an important predictor for poor prognosis in patients with LN.

Exploratory Studies With BT-11: A Proposed Orally Active Therapeutic for Crohn's Disease.

Lanthionine synthetase cyclase-like receptor 2 (LANCL2) is a novel therapeutic target for Crohn's disease (CD). BT-11 is a small molecule that binds LANCL2, is orally active, and has demonstrated therapeutic efficacy in 3 validated mouse models of colitis at doses as low as 8 mg/kg/d. Exploratory experiments evaluated BT-11 in male Harlan Sprague Dawley rats with a single oral dose of 500 mg/kg and 80 mg/kg/d for 14 days (n = 10 rats dosed/group). Treated and control rats were observed for behavioral detriments, and blood and tissues were collected for clinical pathology and histopathological examination. A functional observational battery demonstrated no differences between treated and control groups over multiple times of observation for quantal, categorical, and continuous end points, including posture, in cage activity, approach, response to touch, weight, grip strength, body temperature, and time on a rotarod. Histopathological examination of the brain, kidney, liver, adrenal gland, testes, stomach, small and large intestines, duodenum, pancreas, heart, lungs, spleen, thymus, and rib found no significant differences between the groups. Plasma enzymes associated with liver function were transiently elevated 2 to 4 days after the 500 mg/kg single dose but returned to normal values by 8 days and were not observed at any time in rats given 80 mg/kg/d for 14 days. One hour after oral administration of a single dose of 80 mg/kg, BT-11 had a maximal concentration of 21 ng/mL; the half-life was 3 hours. These experimental results demonstrated that BT-11 is well tolerated in rats, and, with further testing, may hold promise as an orally active therapeutic for CD.

Diagnosis and treatment of autoimmune pancreatitis

Diagnosis and treatment of autoimmune pancreatitis

Helicobacter pylori Clarithromycin Resistance and Treatment Failure Are Common in the USA.

Helicobacter pylori antibiotic resistance leads to frequent treatment failure. However, the current US prevalence of H. pylori clarithromycin resistance and treatment failure is unknown. To determine the prevalence of clarithromycin-resistant H. pylori and its impact on treatment failure in the USA. A multicenter, retrospective, cohort study for clarithromycin-resistant H. pylori was conducted over four academic medical centers in different geographic regions of the USA. Gastric biopsy material, residual from standard clinical pathologic examination, was examined for clarithromycin resistance by DNA sequencing of H. pylori 23S rRNA. One hundred and twenty-four cases of H. pylori gastritis were examined from medical centers in four different geographic regions of the USA. The overall prevalence of clarithromycin resistance was 32.3% (range 23.1-45.8%). There was no significant difference in the prevalence of clarithromycin resistance by study site, gender, age, or race/ethnicity. In a subset of 67 patients that had clinical follow-up data, the overall prevalence of clarithromycin resistance was 31.3%. There was a 2.9-fold increase (p=0.002) in treatment failure for cases with clarithromycin resistance (57.1%) compared to wildtype H. pylori (19.6%). H. pylori clarithromycin resistance in the USA exceeds the estimated 20% prevalence compatible with successful empiric antibiotic therapy. This resistance resulted in a significant rate of treatment failure in all sites surveyed. Empiric therapy in the USA should be used with caution until there is better regional or local determination of H. pylori antibiotic resistance.

Expression of insulin-like growth factor ІI mRNA binding protein 3 (IMP3) in enchondroma and chondrosarcoma

Atypical cartilaginous tumor and enchondroma are similar in histopathologic aspects. Although the clinical course, radiologic and pathologic examinations enable distinction in most cases, difficulties are still encountered by the pathologists. There is no known biomarker to help make a distinction between benign and malignant cartilaginous tumors. Insulin-like growth factor II mRNA binding protein (IMP3) is a member of an oncofetal family of proteins that is expressed in different human malignancies and rapidly emerging as a prognostic and diagnostic marker in surgical pathology. In this study, IMP3 expression was examined by immunohistochemistry in 36 enchondromas and 42 chondrosarcomas of different histologic grades. The results showed that all 36 cases of enchondroma were negative for IMP3, while it was overexpressed in 15 of 42 chondrosarcomas (36%) (P<0.01). Significant higher levels of IMP3 were detected in grade III chondrosarcomas (6 of 7; 85.7%) when compared to low-grade tumors (6 of 19; 31.5% in grade II and 3 of 16; 18.7% in Atypical Cartilaginous Tumor). We proved statistically significant difference in IMP3 expression between enchondromas and ACTs (P=0.025). Our study clearly demonstrated differentiation-dependent expression of IMP3 in chondrosarcoma, and suggests IMP3 as a novel marker for differentiating problematic cases of enchondroma from well-differentiated chondrosarcomas. To our knowledge, this study is the first study to clarify expression of IMP-3 in chondromas and chondrosarcomas.

Placental function assessed visually using half-Fourier acquisition single-shot turbo spin-echo (HASTE) magnetic resonance imaging

IntroductionTo investigate a simple visual assessment method of placental function using half-Fourier acquisition single-shot turbo spin-echo (HASTE) magnetic resonance imaging (MRI). MethodsThe institutional review board approved this retrospective study of fetal MRI in 48 singleton pregnant women for whom placentas had undergone clinical pathological examinations. Two readers independently assessed the placentas using the HASTE scoring system, particularly emphasizing the visualization of the regular two-tone pattern inside and signal intensity (SI) of placental parenchyma referring to SI of the fetal kidney and liver. After categorization using the HASTE scoring system, the associations between the scores and the presence of pathologically proven placental insufficiency or of low birth weight less than the tenth percentile were examined using chi-square tests. The associations between the HASTE scores and the MRI findings previously reported to suggest placental insufficiency, such as placental thickness and placenta to amniotic fluid SI ratio, were also examined using Student t-tests. ResultsThe HASTE scores were associated significantly with the presence of pathologically proven placental insufficiency (P = .003 for reader 1; P = .04 reader 2) and birth weight less than the tenth percentile (P = .005 for reader 1; P = .003 for reader 2). The HASTE scores were associated significantly with the placenta thickness (P < .0001 for both readers) and the placenta to the amniotic fluid SI ratio (P < .0001 for both readers). DiscussionThe HASTE scoring system is feasible for use in clinical assessment of placental function and for diagnosing placental insufficiency.

One case of choriocarcinoma sellar region metastasis and literature review

Chorionic carcinoma is a highly malignant gynecological tumor, frequently originating from trophoblastic cells in the uterus after fertilization. Early erosion releases cancerous cells into the circulation to invade surrounding organs without primary symptoms and signs. One case of choriocarcinoma sellar region metastasis was analyzed, utilizing clinical data, MRI and pathological examinations, and clinical characteristics were summarized. Choriocarcinoma sellar region metastasis is easily misdiagnosed. We examined the literature and original resources to summarize the clinical characteristics of choriocarcinoma sellar region metastasis and discuss available therapies. This case study of a metastasis of choriocarcinoma to the sellar region provides important new data on the incidence and pathology of this rare disease.

Primary diffuse large B-cell lymphoma of endometrium

&lt;p class="BodyText1"&gt;This article was designed to analyze the prognosis and to explore the clinical characteristics and treatment of a case of primary diffuse large B-cell lymphoma (DLBCL) of the endometrium, through a detailed report. &lt;strong&gt;Methods&lt;/strong&gt;: This report was done by analyzing a case through its clinical features, pathological examination and immunophenotyping. We believe that this would allow us to forecast the prognosis of the case. &lt;strong&gt;Case Description&lt;/strong&gt;: The patient was admitted because of irregular postmenopausal vaginal bleeding for more than a month. She underwent a series of surgical procedures that included abdominal hysterectomy, bilateral adnexectomy, pelvic lymph node dissection and enterolysis owing to the assessed pathological results after uterine curettage. The postoperative pathological results showed that it was a DLBCL. &lt;strong&gt;Conclusion&lt;/strong&gt;: Primary DLBCL of the endometrium is rarely reported. Its diagnosis and differential diagnosis mainly depends on pathological examination and immunophenotyping. Radical surgery combined with chemotherapy may be an ideal mode of treatment. The prognosis of the disease has a varied range but radical surgery combined with chemotherapy may improve her quality of life and prolong her survival period.&lt;/p&gt;

Abstract LB-062: XPO1 is a rational target for double and triple-hit aggressive B-cell lymphomas

Abstract Mutation and constitutive expression of MYC and BCL2 and/or BCL6 (a.k.a. double and triple-hit lymphomas) defines subsets of diffuse large B-cell lymphoma (DLBCL) pts with particularly poor outcome. Almost 60% of pts with BCL2 and MYC translocations die within six months of diagnosis due to chemorefractory disease, a prognosis that cannot be overcome with intense chemotherapy. A further hindrance to patient survival is that these double and triple-hit lymphomas are frequently found in the elderly who have limited tolerability to aggressive chemotherapeutic regimens. To identify chemoresistant double and triple-hit DLBCL, we screened 38 DLBCL cell lines for mutations in BCL2, MYC and BCL6 by FISH and response to chemotherapy administration in vitro. We found 3 triple-hit and 2 double-hit DLBCL cell lines. Previous work in our laboratory showed that the nuclear export protein, XPO1, is a critical regulator of MYC, BCL2 and BCL6 mRNA transport in DLBCL. We therefore analyzed XPO1 amplification (by PCR) and expression (by immunoblot) in these cell lines and found that all 5 cells expressed XPO1 at higher levels than centroblasts and that, in at least 2 of them, this was result of gene amplification. Inhibition of XPO1 with selinexor, a Selective Inhibitor or Nuclear Export (SINE) compound, increased nuclear localization of MYC, BCL2 and BCL6 transcripts and consequently decreased their protein expression. Moreover, selinexor administration induced chemosensitization in doxorubicin-resistant DLBCL cells through decreasing DNA damage repair mechanisms as demonstrated by comet assays. To determine the potential extent of DLBCL patients that could benefit from such a treatment, we first analyzed 110 DLBCL patient samples by immunohistochemistry and found that XPO1 expression was increased in 85 cases compared to normal tonsils. Within the cohort analyzed, 6 patients had double or triple hit lymphoma (by FISH) and all overexpressed XPO1. Since this population has higher incidence of chemorefractory disease, we decided to develop a pre-clinical model of this disease using primary patient samples. We developed two patient-derived xenograft (PDX) models representing a double and a triple-hit lymphoma. In both cases XPO1 was also amplified. We compared the molecular and pathological characteristics of 12 generations of PDXs with the original pt sample, and found that protein expression and mutations of these genes were stable. We therefore administered selinexor alone, CHOP alone (cyclophosphamide, vincristine, doxorubicin and dexamethasone) and the combination of selinexor with CHOP to these PDXs. We found that selinexor significantly decreased tumor growth, compared to vehicle or CHOP alone. Moreover, combinatorial treatment indicated that selinexor was able to revert the chemorefractoriness of these DLBCLs, without inducing toxicity by clinical chemistry or pathologic examination. Analysis of selinexor vs. vehicle treated PDXs indicated a decrease in protein levels of MYC, BCL6, BCL2 as well as DNA damage and checkpoint regulators such as CHK1. In summary, selinexor has potent anti-proliferative effects in double/triple-hit DLBCL and can be safely combined with CHOP to enhance cancer cell death. These data present a new therapeutic approach for pts with double/triple hit lymphomas, and provide rational support for the study of selinexor/CHOP combination in clinical trials. Citation Format: Rossella Marullo, ShaoNing Yang, Tami Rashal, Yosef Landesman, Robert Carlson, Sharon Shacham, Leandro C. Cerchietti. XPO1 is a rational target for double and triple-hit aggressive B-cell lymphomas. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-062. doi:10.1158/1538-7445.AM2015-LB-062

A novel pathogenic germline mutation in the adenomatous polyposis coli gene in a Chinese family with familial adenomatous coli.

Familial adenomatous polyposis (FAP) is an autosomal dominant disease manifesting as colorectal cancer in middle-aged patients. Mutations of the adenomatous polyposis coli (APC) gene contribute to both FAP and sporadic or familial colorectal carcinogenesis. Here we describe the identification of the causative APC gene defects associated with FAP in a Chinese pedigree. All patients with FAP were diagnosed by their combination of clinical features, family history, colonoscopy, and pathology examinations. Blood samples were collected and genomic DNA was extracted. Mutation analysis of APC was conducted by targeted next-generation sequencing, long-range PCR and Sanger sequencing. A novel mutation in exon 14-15(c.1936-2148 del) and intron 14 of the APC gene was demonstrated in all FAP patients and was absent in unaffected family members. This novel deletion causing FAP in Chinese kindred expands the germline mutation spectrum of the APC gene in the Chinese population.

Irreversible Electroporation of the Femoral Neurovascular Bundle: Imaging and Histologic Evaluation in a Swine Model

PurposeTo evaluate imaging, histologic changes, and safety of irreversible electroporation (IRE) on the femoral neurovascular bundle in a swine model. Materials and MethodsThe study was approved by the institutional animal ethics committee. IRE was performed on the right femoral neurovascular bundle of 9 swine, which were subsequently sacrificed at 24 hours (n = 4, acute group), 7 days (n = 4, subacute group), or 21 days (n = 1, delayed group). Clinical observation, computed tomography (CT), and pathologic examination were carried out. ResultsAfter the procedure, 7 of 9 subjects were able to stand and walk, and the remaining 2 subjects could eventually do so within 1 week. The femoral vessels were patent on CT and gross examination. There was microscopic evidence of venous thrombosis in 75% of the subacute group. Except for mild perineural inflammation observed in 1 subject in the subacute group, the femoral nerves were intact on gross and histologic examination. Significant damage to the surrounding muscle and soft tissue was identified on CT and histology, manifesting as necrosis, hematoma, and inflammation. ConclusionsThe ablative effect of IRE on muscle and soft tissue manifested as necrosis, hemorrhage, and inflammation. Histologic changes were observed in the perineural tissue and veins in a few subjects. The clinical implication of such changes and safety of clinical use of IRE for lesions encasing the neurovascular bundle in humans are yet to be determined.

Treatment of chronic inflammatory demyelinating polyneuropathy.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is one of the acquired demyelinating neuropathies and is considered to be immune mediated. Diagnosis is typically based on clinical history, neurologic examination, electrophysiologic studies, CSF studies, and pathologic examination. Early diagnosis and treatment is important to prevent irreversible axonal loss and optimize improvement in function. The first-line agents for treatment are intravenous immunoglobulin (IVIg), corticosteroids, and plasmapheresis, which have all been demonstrated to be effective in controlled studies. Studies have not shown a significant difference between these three treatments, and the initial choice of therapy is often based on availability, cost, ease of administration, and side effect profile. If patients do not respond to one of these agents, they may respond to one of the others and sometimes in combination. If the first-line agents are not effective, chemotherapeutic or immunosuppressive agents may be considered. There are limited controlled studies of these modalities, and they are often used in conjunction with a first-line treatment. The majority of patients require long-term therapy to maintain a response and to prevent relapse.

Analysis of clinical and imaging characteristics of infectious sacroiliac arthritis and review of literatures

To study the clinical and imaging characteristics of patients with infectious sacroiliac arthritis. Twenty-one patients diagnosed with infectious sacroiliac arthritis were analyzed retrospectively between 2000 and 2014. The chief complaint was pain in hip and lumbosacral area. Their clinical features, laboratory tests and pathological examination results as well as CT/MRI/PET-CT images were evaluated. There were nine males and thirteen females eighteen (85.7%) patients had unilateral sacroiliac joint involvement. Among these patients, three were diagnosed with brucellosis sacroiliac arthritis (BSI), eight patients with tuberculosis sacroiliac arthritis (TSI), and ten patients with non-brucellosis and non-tuberculosis infectious sacroiliac arthritis (ISI). For those patients with non-brucellosis and non-tuberculosis infectious sacroiliac arthritis, white blood cell count, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were dramatically increased. Twelve patients were diagnosed pathologically including 6 ISI, 2 BSI and 4 TSI. Twelve patients and seventeen patients were scanned by CT and MRI respectively. Two patients undertook PET-CT examination. Antibiotic therapy showed significant therapeutic effects in all patients. Infectious sacroiliac arthritis patients with hip or lumbosacral pain as the chief complaint can be easily misdiagnosed as spondyloarthritis. Comprehensive analysis of clinical features, imaging and laboratory findings is essential for accurate diagnosis.

CT Characterization of Duodenal Gastrointestinal Stromal Tumors.

Diagnosis and staging of duodenal gastrointestinal stromal tumors (GISTs) by noninvasive imaging is critical for effective treatment, but the imaging features of duodenal GISTs remain largely undefined because of their rarity. The purpose of this article was to characterize duodenal GISTs using CT. Thirty-four patients with duodenal GISTs were analyzed by clinical symptom evaluation, pathologic examination, and CT in this retrospective study. Unenhanced and contrast-enhanced examinations were performed in all patients. Imaging characteristics, including the lesion location, size, growth pattern, ulceration, internal components, arterial blood supply, intratumoral arterioportal shunting, intratumoral vessels, rim enhancement, and enhancement patterns were reviewed. The duodenal GISTs were solitary masses with well-defined margins. The average diameter was 7.1 cm. The second portion was the most common site (20/34). Ulceration was a common feature (15/34). Calcification was uncommon (3/34), and mixed growth pattern was more common (26/34). Rim enhancement (24/34) and mixed enhancement pattern (15/34) were common. Arterial blood supply, intratumoral vasculature, and draining veins were all detected and were obvious on the arterial phase. The portal venous trunk and superior mesenteric vein were the main veins into which early arterioportal shunting drained. Primary duodenal GISTs are generally large, well-defined, heterogeneously enhancing, and hypervascular masses with a prominent mixed growth pattern on CT images. Our findings suggest that CT can help depict the origin of the tumoral arteries and draining veins on the arterial phase and may be a key defining diagnostic feature for duodenal GISTs.

Metabolomics analysis and biomarker identification for brains of rats exposed subchronically to the mixtures of low-dose cadmium and chlorpyrifos.

Cadmium (Cd) and chlorpyrifos (CPF) are widespread harmful environmental pollutants with neurotoxicity to mammals. Although the exposure to Cd and CPF at the same time may pose a significant risk to human health, the subchronic combined neurotoxicity of these two chemicals at low levels in the brain is poorly understood. In this study, we treated rats with three doses (low, middle, and high) of Cd, CPF, or their mixture for 90 days. No obvious symptom was observed in the treated animals except those treated with high-dose CPF. Histological results showed that middle and high doses of the chemicals caused neuronal cell damage in brains. GC-MS-based metabonomics analysis revealed that energy and amino acid metabolism were disturbed in the brains of rats exposed to the two chemicals and their combinations even at low doses. We further identified the unique brain metabolite biomarkers for rats treated with Cd, CPF, or both. Two amino acids, tyrosine and l-leucine, were identified as the biomarkers for Cd and CPF treatment, respectively. In addition, a set of five unique biomarkers (1,2-propanediol-1-phosphate, d-gluconic acid, 9H-purine, serine, and 2-ketoisovaleric acid) was identified for the mixtures of Cd and CPF. Therefore, the metabolomics analysis is more sensitive than regular clinical observation and pathological examination for detecting the neurotoxicity of the individual and combined Cd and CPF at low levels. Overall, these results identified the unique biomarkers for Cd and CPF exposure, which provide new insights into the mechanism of their joint toxicity.

Diagnosis and treatment of autoimmune pancreatitis: experience with 100 patients

Autoimmune pancreatitis (AIP) is increasingly recognized as a unique subtype of pancreatitis. This study aimed to analyze the diagnosis and treatment of AIP patients from a tertiary care center in China. One hundred patients with AIP who had been treated from January 2005 to December 2012 in our hospital were enrolled in this study. We retrospectively reviewed the data of clinical manifestations, laboratory tests, imaging examinations, pathological examinations, treatment and outcomes of the patients. The median age of the patients at onset was 57 years (range 23-82) with a male to female ratio of 8.1:1. The common manifestations of the patients included obstructive jaundice (49 patients, 49.0%), abdominal pain (30, 30.0%), and acute pancreatitis (11, 11.0%). Biliary involvement was one of the most extrapancreatic manifestations (64, 64.0%). Fifty-six (56.0%) and 43 (43.0%) patients were classified into focal-type and diffuse-type respectively according to the imaging examinations. The levels of serum IgG and IgG4 were elevated in 69.4% (43/62) and 92.0% (69/75) patients. Pathological analysis of specimens from 27 patients supported the diagnosis of lymphoplasmacytic sclerosing pancreatitis, and marked (>10 cells/HPF) IgG4 positive cells were found in 20 (74.1%) patients. Steroid treatment and surgery as the main initial treatments were given to 41 (41.0%) and 28 (28.0%) patients, respectively. The remission rate after the initial treatment was 85.0%. Steroid was given as the treatment after relapse in most of the patients and the total remission rate at the end of follow-up was 96.0%. Clinical manifestations, laboratory tests, imaging and pathology examinations in combination could increase the diagnostic accuracy of AIP. Steroid treatment with an initial dose of 30 or 40 mg prednisone is effective and safe in most patients with AIP.

Clinical pictures and pathological examination of monochorionic-diamniotic (MD) twin pregnancy

Clinical pictures and pathological examination of monochorionic-diamniotic (MD) twin pregnancy

Regulation of expression of p57KIP2 gene in extravillous trophoblast cells

Regulation of expression of p57KIP2 gene in extravillous trophoblast cells

Clinical manifestations and imaging characteristics of gliomatosis cerebri with pathological confirmation.

To explore the clinical manifestations and imaging characteristics of gliomatosis cerebri to raise the awareness and improve its diagnostic accuracy for patients. Clinical data, imaging characteristics and pathological examination of 12 patients with GC from Jan., 2008 to Jan., 2012 were analyzed retrospectively. Patients with GC were clinically manifested with headache, vomiting, repeated seizures, fatigue and unstable walking, most of whom had more than 2 lesions involving in parietal lobe, followed by temporal lobe, frontal lobe, periventricular white matter and corpus callosum. Magnetic resonance imaging (MRI) showed diffuse distribution, T1-weighted images (T1WI) with equal and low signals and T2-weighted images (T2WI) with bilateral symmetrical high diffuse signals. There was no reinforcement by enhancement scanning and signals were different in diffusion-weighted images (DWI). The higher the tumor staging, the stronger the signals. Pathological examination showed neuroastrocytoma in which tumor tissues were manifested by infiltrative growth in blood vessels and around neurons. In clinical diagnosis of GC, much attention should be paid to the diffuse distribution of imaging characteristics, incomplete matching between clinical and imaging characteristics and confirmation by combining with histopathological examination.