Typical Histopathological Features Research Articles

Pseudomyogenic Hemangioendothelioma Recapitulated in Endothelial Cells from Human Induced Pluripotent Stem Cells Engineered to Express the <i>SERPINE1-FOSB</i> Translocation

Chromosomal translocations are prevalent among soft tissue tumors including those of the vasculature. Pseudomyogenic hemangioendothelioma (PHE) is one such tumor. It has features of endothelial cells (ECs) and a tumor-specific t(7;19)(q22;q13) SERPINE1-FOSB translocation, but has been difficult to study since to date no cell lines have been derived from the tumor. To address this, we engineered the PHE chromosomal translocation into human induced pluripotent stem cells (hiPSCs) using CRISPR/Cas9 and differentiated these into ECs (hiPSC-ECs). Comparison of parental and modified (PHE) lines with the t(7;19)(q22;q13) SERPINE1-FOSB translocation showed (i) elevated expression of FOSB specifically in hiPSC-ECs in vitro and in vivo (ii) increased proliferation and tube formation but decreased endothelial barrier function (iii) transcriptome alterations specific for hiPSC-ECs that reflect typical PHE histopathological features (iv) invasive growth and abnormal vessel formation in mouse after transplantation of the mutated cells. hiPSC-ECs carrying the SERPINE1-FOSB translocation thus recapitulated functional features of PHE and demonstrated that this approach can yield models of translocation-driven tumors for identification of therapeutic targets and deeper understanding of underlying tumorigenic mechanisms.

Peripheral T-Cell Lymphoma, not Otherwise Specified (PTCL-NOS).

Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is a World Health Organization (WHO)-defined diagnostic category within the highly heterogeneous group of mature post-thymic T-cell neoplasms. It is the most common subtype of mature post-thymic T-cell neoplasms globally, accounting for up to 35% of PTCL cases in Europe and North America. PTCL-NOS is a diagnosis of exclusion, comprising several disease entities that differ in biology, clinical presentation, and outcome. The diagnosis of PTCL-NOS is made based on the presence of typical histopathological features of lymphoma, an aberrant T-cell immunophenotype, often with a loss of CD5 and CD7, and a clonal T-cell receptor (TCR) gene rearrangement, in the appropriate clinical context. Unlike other types of T-cell lymphoma, recurrent mutations to assist with the diagnosis have not been identified. Patients often present with advanced stage. Prognosis is poor, with a 5-year overall survival (OS) of 20-30%. Anthracycline-based combination chemotherapy remains the most frequently used frontline strategy, with overall response rates (ORR) of 50-60%, and complete response rates (CRR) of 20-30%. Prospective studies with intent-to-treat analyses have shown that consolidation with high-dose chemotherapy and autologous stem cell transplant (ASCT) results in progression-free survivals (PFS) that compare favorably with historical cohorts and may improve OS in selected patient populations. However, randomized data are still lacking. Over the past decade, therapeutic agents approved in the relapsed and refractory setting have produced response rates of up to 33% and median PFS up to 18 months. Overall, outcomes remain poor and there is a dire need for more effective treatments. This review discusses the latest information on the diagnosis and treatment of PTCL-NOS.

Report of two cases with autoerythrocyte sensitization syndrome

Auto-erythrocyte Sensitization Syndrome, also known as Gardner Diamond syndrome, is characterized by spontaneous painful and repetitive purpura. Here, we report two women aged 14 and 18 years who were diagnosed with auto-erythrocyte sensitization syndrome by typical laboratory, clinical, histopathological features and intradermal skin test. Burning and itching were the major complaints associated with spontaneous ecchymosis. The frequency of attacks in the patient using a specific serotonin re-uptake inhibitor due to migraine was significantly higher than the patient who did not receive psychiatric treatment. It was concluded that careful psychiatric evaluation is important for effective treatment of the disease.

Clinical and histopathological analysis of 313 cases of psoriasis

Objective To analyze clinical manifestations and histopathological features of 6 subtypes of psoriasis presenting mainly as skin manifestations. Methods Clinical and histopathological data were collected from 313 patients with psoriasis in the Department of Dermatology of Xijing Hospital between 2013 and 2017, and analyzed retrospectively. Results Among the 313 patients, there were 31 patients with guttate-type psoriasis mainly induced by upper respiratory tract infections, 60 with plaque psoriasis with the main precipitating factors being upper respiratory tract infections, overexertion, cold weather and so on, 42 with erythrodermic psoriasis induced mainly by the withdrawal of systemic glucocorticoids, 60 with generalized pustular psoriasis with the main precipitating factors being upper respiratory tract infections, pregnancy, drugs and so on, 60 with palmoplantar pustulosis without definite precipitating factors, and 60 with acrodermatitis continua without definite precipitating factors. The 6 subtypes of psoriasis had similar typical pathological manifestations, including parakeratosis, Munro′s microabscess and/or spongiform pustules of Kogoj, thinning or absence of the granular layer, psoriasis-like epidermal hyperplasia, capillary ectasia in the dermal papillae, lymphocytic infiltration and so on. Atypical pathological manifestations were observed in 98 (31%) of the 313 patients, which included 4 with guttate type psoriasis (13%) , 3 with plaque psoriasis (5%) , 12 with erythrodermic psoriasis (29%) , 41 with generalized pustular psoriasis (68%) , 12 with palmoplantar pustulosis (20%) and 26 with acrodermatitis continua (43%) . These atypical pathological manifestations included serous fluid exudation, irregular epidermal hyperplasia, non-neutrophilic spongiosis, keratinocyte necrosis, dermal neutrophilic infiltration and dermal eosinophilic infiltration. Conclusions Different subtypes of psoriasis have different clinical manifestations and similar typical histopathological features. Atypical pathological features can interfere with the diagnosis of psoriasis, and attention should be paid to the differential diagnosis. Key words: Psoriasis; Retrospective studies; Clinical manifestation; Histopathology

Effects of extracts from soothing-liver and invigorating-spleen formulas on the injury induced by oxidative stress in the hepatocytes of rats with non-alcoholic fatty liver disease induced by high-fat diet

OBJECTIVETo investigate effects of the extracts from soothing-liver and invigorating-spleen formulas on the injury due to oxidative stress, mediated by the Nuclear factor-like 2 (Nrf2)-Antioxidant response element (ARE) pathway, in the hepatocytes of rats with non-alcoholic fatty liver disease (NAFLD) induced by high-fat diet. METHODSSoothing-liver and invigorating-spleen formula mixtures were prepared for five groups: normal, model, soothing-liver formula group (SLG), invigorating-spleen formula group (ISG), integrated formula group (IG). The rat model of NAFLD was induced by feeding rats a high-fat diet (HFD). After 16 weeks, the hepatic tissue was examined following Haematoxylin-Eosin (H&E) staining and with Transmission electron microscopy (TEM). Levels of hepatic lipids, serum lipids and hepatic functions were measured using a biochemical analyser. Hepatocytes were isolated from the livers of rats and were identified by cellar immunohistochemistry, cellular immunofluorescence and flow cytometry. The expression levels of Nrf2, Kelch-like epichlorohydrin-associated protein 1 (Keap-1), haeme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) mRNAs were assessed by real-time fluorescence quantitative PCR. Nrf2, Keap-1, HO-1 and NQO1 proteins were measured by Western blotting. Finally, the levels of oxidative stress factors Superoxide Dismutase (SOD), malonaldehyde (MDA) and Glutathione peroxidase (GSH-Px) in hepatocytes were measured by WST-1, TBA and colorimetry. RESULTSThe H & E and TEM results showed that the NAFLD model rats successfully reproduced typical pathogenetic and histopathological features. The liver function and levels of hepatic lipids and serum lipids from the model rats were dramatically increased. Compared with the model group, the levels of hepatic lipids, serum lipids and hepatic function in the treatment groups were ameliorated to different degrees. The yields of purified hepatocytes in each rat were 4-5 × 108. The viability of the isolated hepatocytes was higher than 95%, with a purity over 93.2%. Cellular immunohistochemistry analysis showed that the hepatocytes were brown, while in the cellular immunofluorescence analysis, the hepatocytes showed green fluorescence. The expression levels of Nrf2, Keap-1, HO-1 and NQO1 mRNA and protein in the hepatocytes were significantly higher in the model group than in the normal group (P < 0.05, P < 0.01). Compared with the model group, the expression of Nrf2, Keap-1, HO-1 and NQO-1 mRNAs and proteins in all treatment groups increased, especially in the IG (P <0.01). CONCLUSIONThe extracts from soothing-liver and invigorating-spleen formulas may protect the liver against the injury induced by oxidative stress in hepatocytes by influencing the Nrf2-ARE pathway, which may be the mechanism having the potential for prevention and treatment of NAFLD.

EBV-associated lymphoepithelioma-like thyroid carcinoma with favorable outcome: case report with cytopathologic and histopathologic study

BackgroundLymphoepithelioma-like carcinoma (LELC) is a rare entity among thyroid tumors. Based on the limited number of case reports that exist, the association of Epstein–Barr virus (EBV) with primary thyroid LELCs seems inconsistent.Case presentationWe present a confusing cytological case of lymphoepithelioma-like thyroid carcinoma with expression of EBV. The patient presented with a central neck mass and bilateral lymphadenopathy. Fine-needle aspiration cytology revealed three-dimensional and syncytial fragments of epithelioid cells accompanied by small lymphocytes. The surgical specimen of resected thyroid tumor disclosed typical histopathological features of LELC. Metastatic papillary carcinoma was also discovered in the metastatic lymph nodes. In situ hybridization for EBV-encoded RNA (EBER-ISH) was positive in the tumor cells. Negative immunoreactivity for TTF-1, Pax-8, and CD5 was observed. The patient is currently undergoing regular follow-up and is 1 year and 10 months postresection with no evidence of recurrence.ConclusionsLong-term survival is discussed in relation to this variant of thyroid carcinoma, which might differ in behavior from anaplastic carcinoma. Further investigation is required to elucidate the clinical significance of EBV expression and progression of this unique variant of thyroid carcinoma.

Steroid-associated osteonecrosis animal model in rats

SummaryObjectiveEstablished preclinical disease models are essential for not only studying aetiology and/or pathophysiology of the relevant diseases but more importantly also for testing prevention and/or treatment concept(s). The present study proposed and established a detailed induction and assessment protocol for a unique and cost-effective preclinical steroid-associated osteonecrosis (SAON) in rats with pulsed injections of lipopolysaccharide (LPS) and methylprednisolone (MPS).MethodsSixteen 24-week-old male Sprague–Dawley rats were used to induce SAON by one intravenous injection of LPS (0.2 mg/kg) and three intraperitoneal injections of MPS (100 mg/kg) with a time interval of 24 hour, and then, MPS (40 mg/kg) was intraperitoneally injected three times a week from week 2 until sacrifice. Additional 12 rats were used as normal controls. Two and six weeks after induction, animals were scanned by metabolic dual energy X-ray absorptiometry for evaluation of tissue composition; serum was collected for bone turnover markers, Microfil perfusion was performed for angiography, the liver was collected for histopathology and bilateral femora and bilateral tibiae were collected for histological examination.ResultsThree rats died after LPS injection, i.e., with 15.8% (3/19) mortality. Histological evaluation showed 100% incidence of SAON at week 2. Dual energy X-ray absorptiometry showed significantly higher fat percent and lower lean mass in SAON group at week 6. Micro-computed tomography (Micro-CT) showed significant bone degradation at proximal tibia 6 weeks after SAON induction. Angiography illustrated significantly less blood vessels in the proximal tibia and significantly more leakage particles in the distal tibia 2 weeks after SAON induction. Serum amino-terminal propeptide of type I collagen and osteocalcin were significantly lower at both 2 and 6 weeks after SAON induction, and serum carboxy-terminal telopeptide was significantly lower at 6 weeks after SAON induction. Histomorphometry revealed significantly lower osteoblast surface and higher marrow fat fraction and oedema area in SAON group. Hepatic oedema appeared 2 weeks after SAON induction, and lipid accumulation appeared in the liver of SAON rats 6 weeks after SAON induction.ConclusionThe present study successfully induced SAON in rats with pulsed injection of LPS and MPS, which was well simulating the clinical feature and pathology. Apart from available large animal models, such as bipedal emus or quadrupedal rabbits, our current SAON small model in rats could be a cost-effective preclinical experimental model to study body metabolism, molecular mechanism of SAON and potential drugs developed for prevention or treatment of SAON.The translational potential of this articleThe present study successfully induced SAON in a small animal model in rats with pulsed injection of LPS and MPS. The evaluation protocols with typical histopathologic ON features and advanced evaluation approaches to identify the metabolic disorders of SAON could be used in future rat SAON studies. The SAON rat model is a suitable and cost-effective animal model to study molecular mechanism of SAON and potential drugs developed for prevention and treatment of SAON.

Effect of Soothing Gan (Liver) and Invigorating Pi (Spleen) Recipes on TLR4-p38 MAPK Pathway in Kupffer Cells of Non-alcoholic Steatohepatitis Rats.

To investigate the mechanism of inflflammatory-mediated toll-like receptor 4 (TLR4)-p38 mitogen-activated protein kinase (p38 MAPK) pathway in Kupffer cells (KCs) of non-alcoholic steatohepatitis (NASH) rats and the intervention effect of soothing Gan (Liver) and invigorating Pi (Spleen) recipes on this pathway. After 1 week of acclimatization, 120 Sprague-Dawley male rats were randomly divided into 8 groups using a random number table (n=15 per group): normal group, model group, low-dose Chaihu Shugan Powder (, CHSG) group (3.2 g/kg), high-dose CHSG group (9.6 g/kg), low-dose Shenling Baizhu Powder (, SLBZ) group (10 g/kg), high-dose SLBZ (30 g/kg) group, and low- and highdose integrated recipe (L-IR, H-IR) groups. All rats in the model and treatment groups were fed with a high-fat diet (HFD). The treatments were administrated by gastrogavage once daily and lasted for 26 weeks. The liver tissues were detected with hematoxylin-eosin (HE) and oil red O staining. Levels of liver lipids, serum lipids and transaminases were measured. KCs were isolated from the livers of rats to evaluate the mRNA expressions of TLR4 and p38 MAPK by real-time flfluorescence quantitative polymerase chain reaction, and proteins expressions of TLR4, p-p38 MAPK and p38 MAPK by Western blot. Levels of inflammatory cytokines including tumor necrosis factor α (TNF-α), interleukin (IL)-1 and IL-6 in KCs were measured by enzyme-linked immunosorbent assay. After 26 weeks of HFD feeding, HE and oil red O staining showed that the NASH model rats successfully reproduced typical pathogenesis and histopathological features. Compared with the normal group, the model group exhibited significant increases in body weight, liver weight, liver index, serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol, and aspartate aminotransferase as well as TC and TG levels in liver tissues, and significant decrease in serum level of high-density lipoprotein cholesterol (Plt;0.05 or Plt;0.01), while those indices were significantly ameliorated in the H-IR group (Plt;0.05 or Plt;0.01). Higher levels of TNF-α, IL-1 and IL-6 in KCs were observed in the model group compared with the normal group (Plt;0.01). Significant decreases in TNF-α, IL-1 and IL-6 were observed in the H-SLBZ, H-IR and L-IR groups compared with the model group (Plt;0.05 or Plt;0.01). The mRNA expressions of TLR4 and p38 MAPK and protein expressions of TLR4, p38 MAPK and p-p38 MAPK in KCs in the model group were significantly higher than the normal group (Plt;0.01), while those expression levels in the L-IR and H-IR groups were significantly lower than the model group (Plt;0.05 or Plt;0.01). Inflflammation in KCs might play an important role in the pathogenesis of NASH in rats. The data demonstrated the importance of TLR4-p38MAPK signaling pathway in KCs for the anti-inflflammatory effect of soothing Gan and invigorating Pi recipes.

Catheter Ablation of Ventricular Tachycardia in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy.

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is predominantly an inherited cardiomyopathy with typical histopathological characteristics of fibro-fatty infiltration mainly involving the right ventricular (RV) inflow tract, RV outflow tract, and RV apex in the majority of patients. The above pathologic evolution frequently brings patients with ARVD/C to medical attention owing to the manifestation of syncope, sudden cardiac death (SCD), ventricular arrhythmogenesis, or heart failure. To prevent future or recurrent SCD, an implantable cardiac defibrillator (ICD) is highly desirable in patients with ARVD/C who had experienced unexplained syncope, hemodynamically intolerable ventricular tachycardia (VT), ventricular fibrillation, and/or aborted SCD. Notably, the management of frequent ventricular tachyarrhythmias in ARVD/C is challenging, and the use of antiarrhythmic drugs could be unsatisfactory or limited by the unfavorable side effects. Therefore, radiofrequency catheter ablation (RFCA) has been implemented to treat the drug-refractory VT in ARVD/C for decades. However, the initial understanding of the link between fibro-fatty pathogenesis and ventricular arrhythmogenesis in ARVD/C is scarce, the efficacy and prognosis of endocardial RFCA alone were limited and disappointing. The electrophysiologists had broken through this frontier after better illustration of epicardial substrates and broadly application of epicardial approaches in ARVD/C. In recent works of literature, the application of epicardial ablation also successfully results in higher procedural success and decreases VT recurrences in patients with ARVD/C who are refractory to the endocardial approach during long-term follow-up. In this article, we review the important evolution on the delineation of arrhythmogenic substrates, ablation strategies, and ablation outcome of VT in patients with ARVD/C.

Atypical lung carcinoid metastasis to the pituitary gland

Objective To study clinicopathological features, diagnosis and differential diagnosis of atypical lung carcinoid metastasis to the pituitary gland based on clinical data of one patient. Methods and Results A 81-year-old female presented headache and sudden blindness, and head MRI showed that there was a lesion at the saddle area. The tumor was detected at intrasellar and in grayish red during surgery. The diameter of tumor was 2 cm. The tumor was soft with no envelop at and well-defined margins, and insufficiency in blood supply. The tumor was removed completely along its edge. Under optical microscopy, the tumor was consisted of small round cells of the same size. Tumor cells were distributed around blood vessels in a nest manner or diffuse manner with brisk mitotic activity and focal necrosis. By using immunohistochemical staining, the tumor cells were diffusely positive for synaptophysin (Syn), CD56 and thyoid transcription factor - 1 (TTF - 1), focal positive for cytokeratin (CK) and P53, and negative for growth hormone (GH), prolactin (PRL), adrenocorticotropic hormone (ACTH), follicle stimulating hormone (FSH), thyroid stimulating hormone (TSH), luteinizing hormone (LH), S-100 protein (S-100), thyroglobulin (TG) and calcitonin. Ki?67 labeling index was about 33%. Conclusions Pituitary metastasis is a rare tumor, and only a few cases of atypical lung carcinoid metastasis to the pituitary gland have been reported. Definite diagnosis could be made by history, typical histopathological characteristics and immunohistochemical expressions. DOI: 10.3969/j.issn.1672-6731.2017.09.010

Clinical analysis of eight cases of ulcerative colitis complicated by pyoderma gangrenosum

Objective To investigate clinical manifestations, histopathological features and treatment of ulcerative colitis (UC) complicated by pyoderma gangrenosum (PG) . Methods Data on clinical manifestations, auxiliary examination findings, treatment and prognosis were collected from 8 inpatients with UC complicated by PG in Peking Union Medical College Hospital between July 2009 and July 2016, and analyzed retrospectively. Results Of the 8 cases, 5 were male, and 3 were female. The average age of onset was 30.6 years and 35.1 years in males and females respectively. All the patients developed intestinal symptoms of UC before the onset of PG with an average time interval of 5 years. Moreover, all the patients had active total colonic type UC at the onset of PG, including 6 with moderately active UC and 2 with mildly active UC. PG manifested as painful ulcers in 8 patients, and affected lower limbs in 7 patients. Histopathological examination of skin lesions showed typical characteristics of vasculitis in 5 patients. Five patients were complicated by arthralgia. All the patients were treated with glucocorticoids and 5-aminosalicylic acid agents as the basic therapy, 3 patients received extra treatment with immuno-suppressive agents or minocycline, and 2 with infliximab. Conclusions PG is a severe skin manifestation of UC, commonly occurs in patients with total colonic type UC in the active stage, and mostly affects the lower limbs, with typical histopathological features of vasculitis. Key words: Pyoderma gangrenosum; Colitis, ulcerative; Disease attributes; Treatment outcome; Inflammatory bowel disease

Endolymphatic hydrops in idiopathic intracranial hypertension: prevalence and clinical outcome after lumbar puncture. Preliminary data.

Idiopathic intracranial hypertension is characterized by raised intracranial pressure (ICP) without any underlying pathology, presenting with (IIH) or without papilledema (IIHWOP). Headache, often on daily basis, is the most frequent symptom. Among audiovestibular symptoms, tinnitus and dizziness are commonly reported, while vertigo and hearing impairment are infrequent reports. Endolymphatic hydrops (ELH) is the typical histopathologic feature of Ménière disease, a condition featured by episodes of vertigo, dizziness, fluctuating hearing loss, tinnitus, and aural fullness. Evidences suggest that ICP is transmitted to inner ear. The aim of this study is to investigate the prevalence of ELH symptoms in IIH/IIHWOP and the relationship between the raised ICP and ELH. The prevalence of chronic headache and of ELH symptoms was investigated in a consecutive series of IIH/IIHWOP patients, and a standard audiometry with hearing threshold measurement (pure-tone average-PTA) was performed. Differences in chronic headache and ELH symptoms prevalence and changes of PTA threshold were calculated after ICP normalization by lumbar puncture (LP). Thirty-one patients (17 with IIH and 14 with IIHWOP) were included. Before LP, chronic headache was present in 93.5%. The percentages of patients reporting tinnitus, dizziness, vertigo, and aural fullness were 67.7, 77.4, 22.6, and 61.3%, respectively. Headache frequency as well as ELH symptoms and PTA significantly improved after LP. The improvement of PTA and of ELH symptoms observed after LP in this series of IIH/IIHWOP patients indicates that a raised ICP, a condition known to be involved in the progression and refractoriness of migraine pain, has also a role in ELH. We propose that intracranial hypertension may represent the shared pathogenetic step explaining the large epidemiological comorbidity between migraine and vestibular symptoms, at present conceptualized as "vestibular migraine."

Emergence of tilapia lake virus in Thailand and an alternative semi-nested RT-PCR for detection

The present study reports outbreaks of tilapia lake virus (TiLV), an emerging pathogen causing syncytial hepatitis of tilapia (SHT), in farmed tilapia in Thailand. Occurrence of the virus was confirmed by RT-PCR and nucleotide sequence homology to the TiLV from Israel. Diseased fish exhibited typical histopathological features of syncytial giant cells in the liver examined through H&E and semi-thin sections. Presence of intracytoplasmic viral particles was revealed by TEM. In situ hybridization using a specific DIG-labeled probe derived from a partial genome segment 3 of TiLV genome revealed multiple tissues tropism of the virus including liver, kidney, brain, spleen, gills and connective tissue of muscle. An alternative semi-nested RT-PCR protocol has been developed in this study for disease diagnosis. Additionally, comparative genetic analysis revealed genetic variations of Thailand-originated virus to the Israel TiLV strains, sharing 96.28 to 97.52% nucleotide identity and 97.35 to 98.84% amino acid identity. Outbreaks of TiLV in different continents might signal a serious threat to tilapia aquaculture globally.

Tumor necrosis factor-induced alopecia: alternative pathology and therapy

Tumor necrosis factor (TNF) inhibitors are used to treat Crohn disease and psoriasis. Although they are typically well tolerated, adverse effects include the development of alopecia, and paradoxically, psoriatic lesions. We recently described a woman with Crohn disease who developed alopecia and scalp psoriasis during infliximab therapy. After discontinuing infliximab and beginning oral and topical therapies, her alopecia completely resolved. We compared our experience with that of the Craddock et al. who described a woman with Crohn disease and alopecia secondary to adalimumab therapy. Although the authors described typical histopathologic features of TNF inhibitor-induced alopecia, including decreased sebaceous glands, psoriasiform changes, superficial and deep perifollicular infiltrate of peribulbar lymphocytes, prominent plasma cells, and variable eosinophils, we observed atypical findings that included chronic folliculitis and perifolliculitis with dermal scarring and naked hair shafts in the dermis - reminiscent of folliculitis decalvans. Both patients experienced a complete recovery; however, Craddock et al. described continuing adalimumab therapy and using intralesional triamcinolone acetonide whereas our patient discontinued infliximab therapy, used a combination of topical scalp therapies including betamethasone lotion and mineral oil overnight under occlusion, and began oral minocycline. In conclusion, various histopathologies are observed with TNF-inhibitor induced alopecia and multiple, effective, therapeutic avenues exist for this affliction.

Genomic aberrations frequently alter chromatin regulatory genes in chordoma.

Chordoma is a rare primary bone neoplasm that is resistant to standard chemotherapies. Despite aggressive surgical management, local recurrence and metastasis is not uncommon. To identify the specific genetic aberrations that play key roles in chordoma pathogenesis, we utilized a genome-wide high-resolution SNP-array and next generation sequencing (NGS)-based molecular profiling platform to study 24 patient samples with typical histopathologic features of chordoma. Matching normal tissues were available for 16 samples. SNP-array analysis revealed nonrandom copy number losses across the genome, frequently involving 3, 9p, 1p, 14, 10, and 13. In contrast, copy number gain is uncommon in chordomas. Two minimum deleted regions were observed on 3p within a ∼8 Mb segment at 3p21.1-p21.31, which overlaps SETD2, BAP1 and PBRM1. The minimum deleted region on 9p was mapped to CDKN2A locus at 9p21.3, and homozygous deletion of CDKN2A was detected in 5/22 chordomas (∼23%). NGS-based molecular profiling demonstrated an extremely low level of mutation rate in chordomas, with an average of 0.5 mutations per sample for the 16 cases with matched normal. When the mutated genes were grouped based on molecular functions, many of the mutation events (∼40%) were found in chromatin regulatory genes. The combined copy number and mutation profiling revealed that SETD2 is the single gene affected most frequently in chordomas, either by deletion or by mutations. Our study demonstrated that chordoma belongs to the C-class (copy number changes) tumors whose oncogenic signature is non-random multiple copy number losses across the genome and genomic aberrations frequently alter chromatin regulatory genes. © 2016 Wiley Periodicals, Inc.

Primary hypothyroidism presenting as pituitary hyperplasia with hyperprolactinemia

Objective To discuss the histological characteristics, immunohistochemical phenotypes, diagnosis and differential diagnosis, treatment and prognosis of one case of primary hypothyroidism presenting as pituitary hyperplasia concurrent with hyperprolactinemia. Methods and Results A 29-year-old female presented menoxenia for one year, galactorrhea for 3 months, and headache for one week. Head MRI demonstrated a sellar space-occcupying lesion and a pituitary adenoma was suspected. Therefore, the patient underwent an exploratory surgery via transnasal-sphenoidal approach under general anesthesia. During the surgery the lesion was located in the right side of sella turcica. It was hard, tough and gray with poor blood supply. Under optical microscopy, the acinar cells showed a diffuse hyperplasia, with focal nodular expansion. The boundary between hyperplastic and normal acinus was ill-defined. By using immunohistochemical staining, the hyperplastic cells were diffusely positive for synaptophysin (Syn) and thyroid stimulating hormone (TSH), partially positive for prolactin (PRL), and negative for thyoid transcription factor-1 (TTF-1). Lymphocytes were scatteredly positive for leukocyte common antigen (LCA). Ki-67 labeling index was less than 1%. Pathological diagnosis was pituitary hyperplasia. The final clinical diagnosis was hypothyroidism. The patient took levothyroxine sodium (Euthyrox) 100 μg/d continously, and was well during the 13-month follow-up. Conclusions Preopertive diagnosis of pituitary hyperplasia is difficult．Definite diagnosis could be made by clinical history, typical histopathological characteristics and immunohistochemical phenotypes. Differential diagnosis from pituitary adenoma, especially microadenoma, should be paid attention. DOI: 10.3969/j.issn.1672-6731.2016.04.009

IgG4-related disease: Advances in the diagnosis and treatment.

IgG4-related disease is a rare immune-mediated systemic disease with the capability of involving essentially any organ. Although the presenting clinical features vary substantially according to the speciality to which patients present first, perhaps the most common clinical presentation is that of single or multiple organ enlargement, arousing suspicion of cancer. The disease is frequently diagnosed unexpectedly in pathological specimens or on imaging studies. The diagnostic approach is complex and includes not only IgG4-related tests (serum levels, circulating plasmablasts, and specific immunohistochemical studies), but also clinical, laboratory, and imaging tests as well as the typical histopathological features (lymphocytic infiltration, storiform fibrosis, eosinophilic infiltration, and obliterative phlebitis). IgG4-related tests should not be considered as diagnostic in the absence of an appropriate clinical scenario. Therapeutic approaches reported to date pertain primarily to glucocorticoids, but the use of these medications has not been studied in a controlled or prospective manner. The most current investigational treatment approaches have focused on targeting cells of the B-cell lineage, including B-cell-depleting agents (rituximab) and a non-depleting homodimer monoclonal antibody targeting CD19 and Fc-gamma RIIIb.

Nestin+cells forming spheroids aggregates resembling tumorspheres in experimental ENU-induced gliomas.

Nestin+cells from spheroid aggregates display typical histopathological features compatible with cell stemness. Nestin and CD133+cells found in glioblastomas, distributed frequently around aberrant vessels, are considered as potential cancer stem cells. They are possible targets for antitumoral therapy because they lead the tumorigenesis, invasiveness and angiogenesis. However, little is known about their role and presence in low-grade gliomas. The aim of this work is to localize and characterize the distribution of these cells inside tumors during the development of experimental endogenous glioma. For this study, a single dose of Ethyl-nitrosourea was injected into pregnant rats. Double immunofluorescences were performed in order to identify stem-like and differentiated cells. Low-grade gliomas display Nestin+cells distributed throughout the tumor. More malignant gliomas show, in addition to that, a perivascular location with some Nestin+cells co-expressing CD133 or VEGF, and the intratumoral spheroid aggregates of Nestin/CD133+cells. These structures are encapsulated by well-differentiated VEGF/GFAP+cells. Spheroid aggregates increase in size in the most malignant stages. Spheroid aggregates have morphological and phenotypic similarities to in vitro neurospheres and could be an in vivo analogue of them. These arrangements could be a reservoir of undifferentiated cells formed to escape adverse microenvironments.

Sinusoidal obstruction syndrome

Sinusoidal obstruction syndrome (SOS) is characterized by damage to small hepatic vessels affecting particularly sinusoidal endothelium. Damaged sinusoids can be associated with a partial or complete occlusion of small hepatic veins, hence the previous denomination of hepatic veno-occlusive disease (VOD). Exposure to certain exogenous toxins appears to be specific to this condition and is frequently included in its definition. Typical histopathological features of SOS in a liver biopsy specimen are presented in the text. The purpose of this article is to provide an overview on the different entities corresponding to this general definition. Such entities include: (i) liver disease related to pyrrolizidine alcaloids; (ii) liver injury related to conditioning for hematopoietic stem cell transplantation; (iii) vascular liver disease occurring in patients treated with chemotherapy for liver metastasis of colorectal cancer; and (iv) other liver diseases related to toxic agents.

Invasive Pulmonary Aspergillosis Histologically Mimicking Mucormycosis

Differential diagnosis of invasive aspergillosis from other pulmonary fungal infections including mucormycosis is important because the treatment is pathogen-dependent. Clinically, invasive aspergillosis is often discriminated from other mold infections on the basis of typical histopathologic features in the biopsy specimen. However, biopsy alone is not always complete because different fungal species can display similar histopathologic features. Surrogate markers or molecular-based assays can be useful when the results of conventional diagnostic modalities are conflicting. Here, we present a case of invasive pulmonary aspergillosis histologically mimicking mucormycosis, which was