Reticular Staining Research Articles

Clinical, histopathologic, and immunoarchitectural features of dermatopathic lymphadenopathy: an update.

Dermatopathic lymphadenopathy is a distinctive form of paracortical lymph node hyperplasia that usually occurs in the setting of chronic dermatologic disorders. The aim of this study is to update our understanding of the clinicopathologic and immunophenotypic features of dermatopathic lymphadenopathy. The study cohort was 50 lymph node samples from 42 patients diagnosed with dermatopathic lymphadenopathy. The patients included 29 women and 13 men with a median age of 49 years (range, 12-79). Twenty-two (52%) patients had a dermatologic disorder, including mycosis fungoides (n = 6), chronic inflammatory dermatoses (n = 13), melanoma (n = 1), squamous cell carcinoma (n = 1), and Kaposi sarcoma in the context of human immunodeficiency virus infection (n = 1). Twenty (48%) patients did not have dermatologic manifestations. Lymph node biopsy specimens were axillary (n = 22), inguinal (n = 21), cervical (n = 4), and intramammary (n = 3). All lymph nodes showed paracortical areas expanded by lymphocytes; dendritic cells, including interdigitating dendritic cells and Langerhans cells; and macrophages. Melanophages were detected in 48 (98%) lymph nodes. Immunohistochemical analysis provided results that are somewhat different from those previously reported in the literature. In the paracortical areas of lymph node, S100 protein was expressed in virtually all dendritic cells, and CD1a was expressed in a significantly greater percentage of cells than langerin (80 vs. 35%, p < 0.0001). These results suggest that the paracortical regions of dermatopathic lymphadenopathy harbor at least three immunophenotypic subsets of dendritic cells: Langerhans cells (S100+, CD1a+(high), langerin+), interdigitating dendritic cells (S100+, CD1a+(low), langerin-), and a third (S100+,CD1a-, langerin-) minor population of dendritic cells. Furthermore, in more than 60% of dermatopathic lymph nodes, langerin highlighted trabecular and medullary sinuses and cords, showing a linear and reticular staining pattern, which could be a pitfall in the differential diagnosis with Langerhans cell histiocytosis involving lymph nodes.

A rapid histological preparation method for observation of morphology and composition distribution of tendon collagen fascicle and endotendinium

To explore a rapid histological preparation method to observe morphology and composition distribution of tendon collagen fascicle and endotendinum. Taking porcine superflexor tendon of foot as an example, tendons were sliced into sections with 6 μm by frozen section technology, after which general observation of the section integrity was carried out. After fixed with 10% neutral buffered formalin and performed with HE staining, the tissue integrity and ice crystal formation were observed under microscope. Sections were then divided into 5 groups by different methods of dyeing. Group A: Priodic acid-Shiff (PAS) staining; group B: Masson staining; group C: reticular fibers staining; group D: immunohistochemical and immunofluorescent staining of type Ⅲ collagen; group E: the sections were baked at 65℃ for 10 minutes and stained with Masson. The composition distribution of tendon collagen fascicle and endotendinum in different groups were observed. From general observation, the frozen section of tendon tissue was complete and continuous. Although the tissue integrity in the tendon sections could be seen and no ice crystal was formed, the composition distribution could not be identified by HE staining. The entire tendons in groups A, B, and C were dyed, and the composition distribution of collagen fascicle and endotendinum could not be identified. The endotendinum in group D was stained weakly positive for type Ⅲ collagen alone, and the two components were differentiated dyed but the contrast was not obvious. In group E, the collagen fascicle and endotendinium were differentiated dyed and the two components in tendon tissue were clearly visible. The morphology and the composition distribution of tendon collagen fascicle and endotendinum can be characterized rapidly and accurately, using a combination of baking at 65℃ for 10 minutes and Masson staining after porcine superflexor tendons were sliced by frozen section technology.

Clinicopathological study of reticular fiber staining and Masson trichrome staining for differential diagnosis of benign and malignant uterine smooth muscle necrosis

目的 探讨特殊染色方法在鉴别平滑肌肿瘤非特异梗死与凝固性坏死中的作用，评估其辅助诊断平滑肌肿瘤的良恶性的价值。 方法 收集东部战区总医院病理科2015年至2018年经手术切除存在梗死/坏死的平滑肌肿瘤22例（包括平滑肌肉瘤7例，良性平滑肌瘤15例）作为研究对象，利用特殊染色方法（网状纤维和Masson三色染色）观察存活-坏死组织交界区域是否存在重塑的修复反应，尝试鉴别非特异梗死与肿瘤性坏死。 结果 子宫平滑肌瘤，患者年龄21~65岁，平均年龄43岁。子宫平滑肌肉瘤，患者年龄34~68岁，平均年龄52岁。平滑肌肉瘤的肿瘤性坏死灶存活-坏死组织交界区域大多保留蜂窝状网状纤维结构（5/7），而在平滑肌瘤的梗死交界区仅少部分保留蜂窝状网状纤维结构（3/15）。Masson三色染色显示平滑肌瘤的梗死交界区（14/15）比平滑肌肉瘤的坏死交界区（2/7）中更常见胶原纤维存在。结果比较差异有统计学意义（P<0.05）。 结论 应用网状纤维染色和Masson三色染色观察子宫平滑肌肿瘤存活-坏死组织交界细胞外基质，这一方法可简洁、有效辅助平滑肌肿瘤良恶性的诊断。

Causes of bone marrow dry pumping in patients with hypocytosis or hematocytosis

Objective To analyze some related causes of hypocytosis or hematocytosis with bone marrow pumping. Methods Bone marrow histology, reticular fiber staining and selective immunohistochemical staining were performed in 34 bone marrow pumping patients with hypocytosis or hematocytosis in the Second People's Hospital of Lianyungang from January 2012 to August 2017. Results All the patients showed dizziness, fatigue, splenomegaly, night sweats and bleeding, including primary myelofibrosis (17 cases, 50.0%), chronic myelocytic leukemia (4 cases, 11.8%), acute myelocytic leukemia (2 cases, 5.9%), acute lymphoblastic leukemia (1 case, 2.9%), myelodysplastic syndrome (2 cases, 5.9%), multiple myeloma (2 cases, 5.9%), non-Hodgkin lymphoma with bone marrow infiltration (2 cases, 5.9%), polycythemia vera (1 case, 2.9%) and bone marrow metastatic tumor (3 cases, 8.8%). The bone marrow proliferative degree in primary myelofibrosis group was mainly grade Ⅱ to grade Ⅳ, and the non primary myelofibrosis group was mainly grade Ⅲ to grade Ⅴ, and the differences of proliferative degree component between them were statically significant (χ2= 12.900, P= 0.004). The fibrosis level in primary myelofibrosis group was mainly grade 2 to grade 3, and the non primary myelofibrosis group was mainly grade 1 to grade 2, and the differences of myelofibrosis degree component between them were also statistically significant (χ2= 12.692, P= 0.003). Conclusions Hematological malignancies, especially primary myelofibrosis, are the common causes of bone marrow dry pumping. Bone marrow histology, reticular fiber staining and selective immunohistochemical staining are of great significance in the etiological diagnosis. Key words: Hypocytosis; Hematocytosis; Myelofibrosis; Biopsy, needle

Clinical and laboratory characteristics of chronic neutrophilic leukemia: analyses of five cases

Objective To investigate the clinical characteristics, cell morphology, genetics, gene mutations of the patients with chronic neutrophilic leukemia (CNL). Methods Five CNL patients from the Second Hospital of Shanxi Medical University between May 2011 and May 2017 who conformed to 2016 World Health Organization (WHO) diagnostic criteria were retrospectively analyzed from clinical characteristics, laboratory features and treatment methods. Results The peripheral blood white blood cell count (WBC) of 5 CNL patients was significantly increased, and the average WBC was 81.26×109/L [(29-217)×109/L]. Morphological analysis of peripheral blood cell showed a sustained increasing number of matured neutrophilia (0.80-0.85). Neutrophil alkaline phosphatase (NAP) activity was increased (144-266). Bone marrow cell morphology typically showed granulocyte proliferation without obvious dysplasia. Gene detection showed 3 patients with CSF3R T618I mutation and 2 patients with JAK2 V617F mutation in 5 WHO-defined CNL patients. Bone marrow biopsy with reticular staining showed that marrow fibrosis (MF) degree in patients with JAK2 V617F mutation (MF≥2) was higher than that in patients with CSF3R T618I mutation(MF<2). Conclusions CNL is a rare type of chronic leukemia, and CSF3R T618I mutation is a specific diagnostic index for CNL. JAK2 V617F mutations alone may be related to myelofibrosis, which remains to be further studied. Key words: Leukemia, myeloid, chronic-phase; Cellular morphology; Genes; Receptors, colony-stimulating factor; Janus kinase 2

Sellar/suprasellar extraventricular neurocytoma

Objective To explore the clinicopathological features of extraventricular neurocytoma located in the sellar/suprasellar region. Methods The clinical manifestations, neuroimaging, histopathological, immunohistochemical and molecular genetic features were retrospectively analyzed in one case of sellar/suprasellar extraventricular neurocytoma, and the related literatures were reviewed. Results A 27-year-old female presented with intermittent headache, accompanied by blurred vision for 5 months. Head MRI demonstrated a mass with a well-defined margin measuring 3.80 cm × 2.50 cm × 3.40 cm located in the sellar/suprasellar region. The tumor showed isointense to hyperintense signals on T 1 WI and hyper-hypointense mixed signals on T 2 WI, and slightly hyperintense signal on diffusion-weighted imaging (DWI). The pituitary was not shown. A transsphenoidal sellar tumor resection, cerebrospinal fluid (CSF) rhinorrhea repairing and optic decompression were performed. The mass was lightly yellow and tough with abundant blood supply and filled with old hemorrhage. The pituitary tissue was pushed to the left rear. Microscopy examination showed a diffuse invasive growth pattern with neuropil background in some area. The tumor cells were uniform on size and shape with round to oval, exquisite and hyperchromatic nuclei. No mitosis was found. Immunohistochemical staining showed the tumor cells were positive for neuronal nuclei (NeuN) and thyroid transcription factor-1 (TTF-1) in nuclei, calretinin (CR) in nuclei and cytoplasm, synaptophysin (Syn), chromogranin A (CgA), E-cadherin, matrix metalloproteinase-9 (MMP-9) in cytoplasm, and focally positive for S-100 protein (S-100) in nuclei, and neurofilament protein (NF), cytokeratin 8 (CK8) and vimentin (Vim) in cytoplasm. The Ki-67 labeling index was about 3%. The tumor tissue was negative for reticular fiber staining. Molecular genetic analysis showed that isocitrate dehydrogenasel (IDH) gene was not mutated, and 1p/19q was intact in tumor cells. The final pathological diagnosis was extraventricular neurocytoma, WHO grade Ⅱ. Conclusions Extraventricular neurocytoma located in the sellar/suprasellar region is very rare. The histological features are similar to central neurocytoma in ventricle. Tumor cells were in diffusely invasive growth and were uniform in size and shape, with round nuclei. Fibrillary areas mimicking neurophil and branching thin-walled capillaries can be seen. The differential diagnosis includes pituitary adenoma, oligodendroglioma, clear cell ependymoma, and so on. DOI: 10.3969/j.issn.1672-6731.2017.12.009

The Development of Intestinal Preservation Injury

The efficient translation of various experimental findings is hampered by interspecies (or even inter-strain) differences that may often invalidate findings, mechanisms or therapeutic approaches. Intestinal preservation/reperfusion injury is a field where rodents were extensively used yet any eventual clinical application would require validation in large animal models. We compared the development of tissue injury in rat and porcine intestines undergoing static cold storage (SCS) in histidine-tryptophane-ketoglutarate (HTK) solution. Methods: Standard procurement and perfusion of the small intestine was performed in Sprague Dawley rats and Landrace pigs (N=7 in each group). At 8h, 14h and 24 hours’ tissue samples were obtained and assessed for tissue damage (Chiu/Park score), apoptosis (active caspase-3) and tissue expression of ZO-1, claudin-3 and villin (immunofluorescence). Results: Rats showed a moderate mucosal injury (median Chiu/Park grade 3) already after 8h while pigs showed normal or near-normal histology (median grade 1). Histology remained significantly superior in pigs after 14h and 24h (see figure). Rats had advanced mucosal injury while only mild/moderate mucosal injury (median grade 2) was noted in pigs after 24h of SCS. Apoptotic enterocytes were abundant in rat but not pig intestines after 14 hours of SCS. After 14 hours of SCS, immunofluorescence revealed the virtual absence of ZO-1 staining in the rat but not in porcine intestines where a strong signal was detected even after 24 hours of SCS. Claudin-3 expression gradually changed from reticular staining on the basolateral membrane to a combined (membrane & cytoplasmic) signal in both species (albeit faster in rats). Conclusions: Pig intestines are significantly more resilient to preservation injury than rat intestines and longer SCS should be considered to attain a visible histological injury. The sequential alterations of certain molecular targets could serve as surrogate injury markers.Figure

Clinicopathologic characteristics of plasma cell myeloma with marrow fibrosis

Objective: To study the clinicopathologic features of plasma cell myeloma(PCM) with bone marrow fibrosis (MF). Methods: The clinicopathologic data of 175 cases of newly diagnosed PCM patients were retrospectively analyzed. Based on reticular fiber staining, these cases were divided into PCM-MF and non-PCM-MF groups. Results: Sixty-three cases were PCM-MF(36%), 112 were non-PCM-MF (64%). No statistical difference in gender, age, hemoglobin level, platelet counts, the classification of immunoglobulin, ISS staging, immunohistochemical phenotypes and genetic features was found between PCM-MF and non-PCM-MF groups (P>0.05). Compared to non-PCM-MF group, lactate dehydrogenase (LDH)level and renal impairmentrate were higher in PCM-MF group (P<0.05). The degree of bone marrow hyperplasia, the percentage of myeloma cells and cells with plasmablastic morphology were significantly higher in PCM-MF group(P<0.05). Conclusion: The higher LDH level, renal impairment rate, and more significant bone marrow hyperplasia, proliferation of plasma cells and plasmablastic myeloma cells infiltration indicate poor prognosis of PCM-MF patients.

Transglutaminase 2 strongly binds to an extracellular matrix component other than fibronectin via its second C-terminal beta-barrel domain.

Transglutaminase 2 (TG2) is a ubiquitous crosslinking enzyme present in both intra- and extracellular in many cell types and tissues. TG2 is upregulated upon cellular stress or injury, and extracellular TG2 is implicated in several human diseases, including celiac disease. However, incomplete knowledge about extracellular TG2 biology limits our understanding of how TG2 is involved in disease. Here, we demonstrate that binding of TG2 to the ECM of small intestinal tissue sections is the sum of binding to fibronectin (FN) via its N-terminal domain and binding to an abundant, novel extracellular matrix (ECM) interaction partner via its second C-terminal beta-barrel domain. The latter interaction dominates and gives rise to the characteristic reticular staining pattern of extracellular TG2. Of relevance for celiac disease, we show that self-multimerized TG2 does not efficiently deposit in the intestinal ECM, and TG2 complexes may thus become free-floating antigens in tissues in contrast to monomeric TG2 that would readily become sequestered by the ECM. Upon injection of monoclonal antibody targeting the FN-binding site, we observe antibody deposition on extracellular TG2 in cryosections, suggesting that the FN-binding site of TG2 is exposed in vivo. This would explain how and why celiac autoantibodies recognizing the FN-binding site of TG2 can bind TG2 in vitro, in situ as well as in vivo.

Pathological characteristics and clinical effect of autoimmune hepatitis after liver transplantation

Objective To investigate the pathological characteristics and clinical effect of autoimmune (AIH) after liver transplantation. Methods The retrospective descriptive cross-sectional study was adopted. The clinicopathological data of 14 patients with AIH who underwent liver transplantation at the First Affiliated Hospital of Xi′an Jiaotong University between June 2011 and December 2015 were collected. Fourteen patients underwent orthotopic liver transplantation, specimens of total liver resection from 14 patients and aspiration specimens from liver allografts of 6 patients with severely abnormal liver function after liver transplantation were collected and detected by hematoxylin-eosin (HE) staining. Specimens of total liver resection continued to detect by reticular fiber staining and immunohistochemistry. The tissues construction was observed by light microscopy. Observation indicators included (1) intra- and post-operative situations, (2) results of pathological examination, (3) follow-up. The follow-up using outpatient examination and telephone interview was performed to detect the situations of immuno-suppressive therapy and survival of patients up to March 2016. Measurement data were represented as average (range). Results (1) Intra- and post-operative situations: all the 14 patients with AIH underwent successful liver transplantation without perioperative death. The operation time, duration of anhepatic period of liver transplantation, volume of intraoperative blood loss and duration of hospital stay were 402 minutes (range, 353-405 minutes), 50 minutes (range, 42-60 minutes), 2 800 mL (range, 1 325-4 050 mL) and 19 days (range, 12-24 days), respectively. Of 14 patients with AIH after liver transplantation, 6 were complicated with pulmonary infection, 2 with acute rejection, 2 with bile duct strictures and 1 with acute renal failure, and they were improved by symptomatic treatment. (2) Results of pathological examination: HE staining of specimens of total liver resection showed that different levels of hepatitis were detected in 14 patients, lymphocytes penetration phenomena in 14 patients, lymphoplasmacytic interface hepatocyte necrosis in 9 patients, infiltration of plasma cells in 9 patients, spotty and piecemeal necroses in 5 patients and rosettes-like structure in 4 patients. HE staining of specimens of liver allografts showed that lymphoplasmacytic interface hepatocyte necroses were detected in 4 patients, rosettes-like structure in 4 patients, cholestatic cirrhosis in 3 patients, mildly acute rejection in 2 patients and recurrence of AIH in 1 patient. Reticular fiber staining: fibrous tissues were proliferative in the portal area and then separated and surrounded hepatocytes to form pseudolobule structure. Immunohistochemistry: inflammatory cells infiltrated by liver tissues were composed of T cells with mainly positive CD3 and CD8 and with few positive CD4. (3) Follow-up: 14 patients were followed up for 26 months (range, 3-57 months). Fourteen patients received regular immuno-suppressive therapy. During follow-up, 1 patient was complicated with primary transplants nonfunction, 2 had AIH recurrence and 3 were dead. Conclusions Patients with AIH should enhance hormone therapy due to high incidences of bile duct complications and pulmonary infection after liver transplantation. Lymphoplasmacytic interface hepatocyte necrosis and rosettes-like structure probably have worse prognosis. Dysfunction of Regulatory T cells (T-reg) may be a prognosis predictor for AIH after liver transplantation. Key words: Autoimmune hepatitis; Liver transplantation; Pathology; Prognosis

Pleomorphic xanthoastrocytoma with anaplastic features

Objective To explore the clinical pathological characteristics, immunophenotyping, diagnosis and differential diagnosis and prognosis of pleomorphic xanthoastrocytoma (PXA) with anaplastic features. Methods HE staining was used for histological observation. The expressions of glial fibrillary acidic protein (GFAP), vimentin (Vim), CD34, epithelial membrane antigen (EMA), progestrone receptor (PR), neurofilment protein (NF), neuronal nuclei (NeuN), synaptophysin (Syn), Nestin (Nes), S-100 protein (S-100), P53 and Ki-67 labeling index were detected by immunohistochemical method. BRAF mutation was detected by polymerase chain reaction (PCR) amplification. Results A 43-year-old male patient presented with repeatedly paroxysmal tic of limbs and disturbance of consciousness. Cranial MRI revealed multiple abnormal signals in left temporo-occipito-parietal lobe and posterior horn of lateral ventricle, with unclear borderline and cystic degeneration. Surgical removal of the lesion was performed. Histologically, the tumor was biphasic. One part was composed of spindle cells arranged in fascicles or as running water, with weird multinuclear giant cells. Abundant vacuolated lipidized cytoplasm could be seen. Mitosis and map-like necrosis were noted. Another part revealed the tumor cells were consistent in size and uniform in distribution, with loose background tissue. Immunohistochemistry showed tumor cells were diffusely positive for GFAP, Vim, S-100, Nes, CD34 and P53, and negative for EMA, Syn, NeuN and NF. Ki-67 labeling index was about 15%. Reticular fiber staining showed abundant reticular fibers in the tumor tissue. BRAF mutation detected by PCR amplification was not found. Conclusions Classified as grade Ⅱ in the World Health Organization (WHO) classification, the prognosis of PXA is good. A diagnosis of PXA with anaplastic features should be considered when the tumor demonstrates mitotic activity > 5/10 high power field (HPF) and/or areas of necrosis. The differential diagnosis from glioblastoma multiforme and gaint cell glioblastoma should be paid attention, as all of them contain variable numbers of pleomorphic astrocytes, in order to avoid overtreatment. DOI: 10.3969/j.issn.1672?6731.2015.08.010

Alveolar soft-part sarcoma in paranasal sinuses

Objective To investigate clinicopathological features, immune phenotype, diagnosis and differential diagnosis of alveolar soft-part sarcoma (ASPS) in paranasal sinuses. Methods Retrospective study of clinical manifestations, histopathological features and immunohistochemical features was conducted in one case of ASPS in paranasal sinuses. Results A 28-year-old female presented with bulging forehead for 2 months. MRI revealed a well-circumscribed lesion in left frontal and ethmoid sinuses extending to anterior skull base that showed slightly hyperintense signal on T 1 WI and hypointense signal on T 2 WI without obvious enhancement after contrast administration. The patient subsequently underwent endoscopic open surgery on left ethmoid and bilateral frontal sinuses and performed partial resection of the lesion. Three months after the initial surgery, the patient received reoperation for total removal of residual lesion and reconstructive surgery of anterior skull base. Adjuvant chemotherapy and radiotherapy were not administered. Histologically, the tumor was composed of epithelioid cells arranged in organoid nests and/or alveolar structures varying in size and shape, which were separated by connective tissue richly containing sinusoidal vascular channels. The tumor cells were generally large-sized, round, oval or polygonal with abundant eosinophilic granular or translucent vacuolated cytoplasm. The nuclei showed round or oval shape containing centrally placed and obvious nucleoli. The presence a lot of mono- or multi-nuclear giant cells served as another striking feature. Mitotic activities were rare. Reticular fiber staining indicated that reticular fibers surrounded the nest of tumor cells, and diastase-resistant periodic acid-Schiff (PAS)-positive crystalline inclusions were identified within the cytoplasm of tumor cells. Immunohistochemically, the tumor cells were reactive for TFE3, while were negative for glial fibrillary acidic protein (GFAP), melanophore markers [HMB45, Melan-A and S-100 protein (S-100)], and epithelial markers [cytokeratin (CK) and epithelial membrane antigen (EMA)]. Ki-67 labeling index was low (2%). The patient remained well without recurrence 15 months after the second surgery. Conclusions ASPS is a rare malignant tumor that tends to occur in adolescents. The tumor is predominantly located in deep soft tissues, such as legs and buttocks. ASPS of paranasal sinus and/or extending to skull base is extremely rare. The accurate diagnosis of ASPS mainly depends on histological and immunohistochemical features, and should be considered in differential diagnosis including the similar morphological pattern of primary or metastatic neoplasms. ASPS is characterized by ASPL-TFE3 gene fusions, and TFE3 protein is a specific marker for ASPS which displays nuclear labeling with TFE3 by immunohistochemistry. DOI: 10.3969/j.issn.1672-6731.2015.07.012

Mitotically active cellular fibroma of ovary: a clinicopathologic analysis

To study the clinicopathologic characteristics of mitotically active cellular fibroma (MACF) of the ovary. The clinicopathologic features of 11 cases of MACF from 2008 to 2012 years were retrospectively reviewed and immunohistochemic EnVision method was performed. The age of patients ranged from 21 to 65 years (mean = 46 years). The maximum tumor diameter varied from 6 to 16 cm (mean = 9.8 cm). The tumors were densely cellular and composed of intersecting bundles of spindle cells, sometimes associated with storiform pattern. The mitotic count ranged from 4 to 20 per 10 high-power field (mean = 8.4). Atypical mitotic figures were not identified and coagulative tumor necrosis was not found. There was at most mild to moderate degree of nuclear atypia. Immunohistochemically, 8 cases showed positive stain for vimentin and 5 cases expressed diffusely or focally WT-1. In 6 cases, Ki-67 positive index ranged from 5%-30%, including 1 case (10%), and 1 case (30%) in which mitotic figures were 20/10 HPF. CK,AE1/AE3, CD117, CD34, CD99 and desmin were negative in the detected 5 cases. Reticular fiber staining in 2 cases showed dense reticular fibers enveloping individual tumor cells. Ten patients who followed-up range from 4 to 38 months were alive without evidence of recurrence or disease progression. One patient was alive with local recurrence 94 months after surgery. Cellular fibromatous neoplasm with mitotic count of ≥ 4/10 HPF but relatively bland nuclear features should be considered as MACF rather than ovarian fibrosarcoma. MACF is a group of ovarian tumor which carries a low malignant potential and occasional chance of recurrence.

Pathology of hepatic iron deposition in hemochromatosis

To identify the type of iron deposition and describe its amount, distribution and associated lesions, in order to support an etiologic diagnosis for hemochromatosis. Hematoxylineosin (HE) stain, reticular fiber stain, Masson's stain and Perl's iron stain were used to assess liver biopsies from 31 patients with hemochromatosis. The Ishak scoring system and Deugnier scoring system were used to assess the histological change in liver and to semi-quantify the excess of hepatic iron. Genetic testing results were received from a portion of the patients and used in analysis. One patient had hereditary (-HFE) hemochromatosis complicated with Gilbert's syndrome, for which the pattern of iron deposition was similar to that of the four patients with Gilbert's syndrome. Iron accumulation appeared as fine granules predominating at the biliary pole of cells and was distributed throughout the lobule with a decreasing gradient spanning from the periportal to centrolobular areas. Mild chronic inflammation was found to be commonly associated with low stage fibrosis.One patient had HFE hemochromatosis complicated with hepatitis B virus infection, and the pattern of iron deposition resembled that in the eight patients with viral hepatitis, wherein the deposition was mainly in the sinusoidal cells and/or portal macrophages. Histological grading and fibrosis staging differed among patients. The five patients with blood disordered showed iron accumulation mainly in the periportal hepatocytes, but mesenchymal iron deposits were also present. The grade of inflammation, as well as of fibrosis,was mild. The five patients with alcoholic disease and the five patients with drug-induced hepatitis showed hepatic iron deposition in swollen or ballooned hepatocytes. The two patients with excessive iron supply showed iron deposition localized within the parenchymal and mesenchymal cells. Etiologic diagnosis of hemochromatosis relies on both the type of iron deposition and the nature of associated lesions. Liver biopsy is necessary for both diagnosis and prognosis.

Clinical and histopathologic features of drug-induced autoimmune hepatitis

Objective To analyze the clinical and histological features of drug-induced autoimmune hepatitis (DI-AIH).Methods From January 2008 to June 2011,five patients with auto-immune hepatitis (AIH),having a definitive history of medicine taking prior to the onset of disease and accepted liver biopsy were retrospectively analyzed.The general information was collected,which included gender,age,onset of the disease,medication,clinical manifestations,treatment and follow-up.The laboratory findings were also collected,which included total bilirubin (TBil),direct bilirubin (DBil),alanine transaminase (ALT),aspartate transaminase (AST),alkaline phosphatase (ALP),gamma glutamyl transpeptidase (GGT),globulin,γ-globulin percentage,albumin (Alb),eosinophils,antinuclear antibodies,antimitochondrial antibodies,anti-smooth muscle antibodies and the type of live injury.The liver tissue sections of patients were stained with hematoxylin-eosinstaining (HE) and reticular fiber staining and then pathological changes were observed.Patients with DI-AIH were scored with AIH scoring scale.Results All five patients with DI-AIH were female,average age was 48.0--+7.5.Prior to the onset of disease,all patients had taken Chinese traditional medicine.Anorexia and fatigue were the most common clinical symptoms.Among laboratory findings,the level of ALT ((795.0+467.4) U/L),AST ((730.44-451.5) U/L),TBil ((80.3-+ 64.1) μmol/L) and DBil ((65.2 +_ 58.0) μmol/L) significantly increased.One patient was antinuclear antibody positive.One patient had drug-induced liver injury,pathological features were spotty necrosis of liver cells,liver tissue eosinophil infiltration and liver cell microbubble type degeneration.All the patients had interface hepatitis,periportal infiltration of lymphocytes or lymphocytes-plasma cells,liver cells adjacent to lesion showed rosette-like structure.All the patients received glucocorticoid treatment.After glucocorticoid withdrawal,the liver function was normal during the follow-up period.Conclusion There are no specificity of clinical manifestations,laboratory findings and histological features in patients with DI-AIH. Key words: Hepatitis, autoimmune; Drugs, Chinese herbal; Biopsy; Laboratory techniques and procedures

Arresting a Torsin ATPase Reshapes the Endoplasmic Reticulum

Torsins are membrane-tethered AAA+ ATPases residing in the nuclear envelope (NE) and endoplasmic reticulum (ER). Here, we show that the induction of a conditional, dominant-negative TorsinB variant provokes a profound reorganization of the endomembrane system into foci containing double membrane structures that are derived from the ER. These double-membrane sinusoidal structures are formed by compressing the ER lumen to a constant width of 15 nm, and are highly enriched in the ATPase activator LULL1. Further, we define an important role for a highly conserved aromatic motif at the C terminus of Torsins. Mutations in this motif perturb LULL1 binding, reduce ATPase activity, and profoundly limit the induction of sinusoidal structures.

Epithelioid malignant peripheral nerve sheath tumor: a case report and review of literature

Background Epithelioid malignant peripheral nerve sheath tumor (EMPNST) is a rare malignant soft tissue tumor, and is more common in adult male. EMPNST originates from nerve, mainly located in the limbs, head and neck, and spine. It is an aggressive tumor with high tendency for local recurrence, and about half of the cases appear distant metastasis. This paper aims to investigate the clinicopathological features of cervial EMPNST. Methods and Results A 48-year-old male mainly presented weakness of limbs, expecially left lower extremty with ankle swelling. MRI showed space-occupying lesion in segment C3-5, considering recurrence of intraspinal tumor 2 years after operation. Tumor resection, repairing of spinal dura mater and laminectomy were made from inion to C7 level. It was found during the surgery that most part of the tumor was located in front of C3-5 spinal nerve, left intraspinal and outside of dura mater. Because part of the tumor grew through the opening of titanium plate, the tumor could not be totally removed. According to postoperative histomorphological observation, tumor cells arranged in sheets or nests, and were separated by fibrous tissue. Most tumor cells were epithelioid, while small part of tumor cells were fusiform. Frequent mitotic activity was found, and part of the region appeared focal necrosis. Immunohistochemical staining showed that tumor cells were positive for pan cytokeratin (PCK), epithelial membrane antigen (EMA), vimentin (Vim), synaptophysin (Syn), chromogranin A (CgA), and S-100 protein (S-100); and were negative for actin, desmin (Des), progestrone receptor (PR), glial fibrillary acidic protein (GFAP), CD34, CD31 and HMB45; Ki-67 labeling index was above 25% . Reticular fiber staining showed that the epithelioid cell nests were surrounded by reticular fibers. Fluorescence in situ hybridization (FISH) detection showed negative for SS18 gene translocation. Combining with the history, the final pathological diagnosis was cervical EMPNST. Conclusion EMPNST lacks of morphological characteristics, and needs to be differentiated from a variety of benign or malignant tumors exhibiting epithelioid features. It is considered that clinical materials, morphological features and immunophenotype are helpful to avoid confusion with other similar lesions. S-100 is not a specific marker, but is a valuable diagnostic index. PCK and EMA can present strongly positive expression. doi：10.3969/j.issn.1672-6731.2013.11.008

Active role of the predecidual-like zone in endometrial shedding in a mouse menstrual-like model

Cyclic shedding of the endometrium is unique to menstruating species. The status of the decidua in mouse menstrual-like models seems to differ from that of the predecidua in humans before endometrial breakdown. The aim of this study was to determine how this difference in decidual status is related to endometrial breakdown. A mouse menstruallike model was generated by pharmacological progesterone withdrawal. Histomorphological analysis and reticular fiber staining were used to evaluate endometrial status. In situ zymography was used to determine the localization of active collagenase and gelatinase. The functional endometrial layer containing the mature decidual-like zone (MDZ) and predecidual-like zone (PZ) underwent breakdown. The reticular fibers underwent disruption and fragmentation and became loose or disappeared at 12 h in the PZ, where active collagenase and gelatinase were limited. The reticular fibers were visibly reduced at 24 h in the MDZ, where active collagenase was detected. A few reticular fibers remained; however, the functional layer had sloughed into the lumen of the uterus. The results showed that reticular fibers of the PZ are actively degraded during endometrial shedding.

Diffuse capillary malformation with overgrowth: A clinical subtype of vascular anomalies with hypertrophy

Categorization of vascular anomalies with overgrowth is evolving rapidly with the aid of massively parallel genomic sequencing; however, accurate clinical diagnosis is still essential. We identified a group of patients with an extensive, diffuse, reticulate capillary malformation (CM) and variable hypertrophy without major complications. We sought to study a subset of patients with diffuse CM to better define prognosis and management. Chart review identified 73 patients with diffuse CM who did not fit the criteria for known disorders with CM and/or overgrowth. Soft-tissue or bony overgrowth did not correlate with location, morphology, or intensity of the vascular stain. Patients required periodic follow-up to monitor for leg length discrepancy. They were found to exhibit normal neurologic development and proportionate overgrowth rather than progressive, disproportionate asymmetry or vascular complications. This retrospective review was limited to observations documented at clinic visits; these patients require long-term assessment. Further studies are necessary to accurately assess Wilms tumor risk and clinical outcomes in older adults. We propose the term "diffuse capillary malformation with overgrowth" to designate this extensive reticular vascular staining with proportionate overgrowth. We differentiate diffuse capillary malformation with overgrowth from other disorders with CM and hypertrophy.

Subcellular localization and function of an epitope-tagged p7 viroporin in hepatitis C virus-producing cells.

The hepatitis C virus (HCV) viroporin p7 is crucial for production of infectious viral progeny. However, its role in the viral replication cycle remains incompletely understood, in part due to the poor availability of p7-specific antibodies. To circumvent this obstacle, we inserted two consecutive hemagglutinin (HA) epitope tags at its N terminus. HA-tagged p7 reduced peak virus titers ca. 10-fold and decreased kinetics of virus production compared to the wild-type virus. However, HA-tagged p7 rescued virus production of a mutant virus lacking p7, thus providing formal proof that the tag does not disrupt p7 function. In HCV-producing cells, p7 displayed a reticular staining pattern which colocalized with the HCV envelope glycoprotein 2 (E2) but also partially with viral nonstructural proteins 2, 3, and 5A. Using coimmunoprecipitation, we confirmed a specific interaction between p7 and NS2, whereas we did not detect a stable interaction with core, E2, or NS5A. Moreover, we did not observe p7 incorporation into affinity-purified virus particles. Consistently, there was no evidence supporting a role of p7 in viral entry, as an anti-HA antibody was not able to neutralize Jc1 virus produced from an HA-p7-tagged genome. Collectively, these findings highlight a stable interaction between p7 and NS2 which is likely crucial for production of infectious HCV particles. Use of this functional epitope-tagged p7 variant should facilitate the analysis of the final steps of the HCV replication cycle.