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Background Allogeneic hematopoietic stem cell transplant for myeloid neoplasms with increased fibrosis is uncommon; morphologic features posttransplant can be concerning for persistent disease. Methods In this retrospective study, we identified 22 patients transplanted for myeloproliferative neoplasms or chronic myelomonocytic leukemia with fibrosis at our institution, and reviewed slides from pretransplant and posttransplant bone marrow biopsies. Clinical features and results of molecular, chimerism, and cytogenetic studies were retrieved from the medical record. Results Pretransplant bone marrow biopsies commonly exhibited hypercellularity, atypical megakaryocytes, and reticulin fibrosis. At day 100, 36% of biopsies had reticulin grade >MF1 and 33% of those tested had positive molecular studies, with no significant associations between day 100 marrow characteristics and molecular profile or peripheral count recovery times. In the 1 year posttransplant biopsies (n = 12), 7 of 9 had negative molecular studies; of these, none had reticulin grade >MF1, 1 had trichrome 1+, 2 had atypical megakaryocytes, and 1 was hypercellular. Conclusions Supporting recent literature, our study indicates that persistent day 100 reticulin fibrosis/collagen deposition does not show an association with day 100 molecular status. Our study additionally provides data for 12 patients with 1 year posttransplant marrow biopsies, with the majority of those lacking either increased fibrosis or molecular evidence of persistent disease. [ABSTRACT FROM AUTHOR]

Abstract Background Current diagnostic criteria of adrenocortical neoplasms are mostly based on morphology. The utility of immunohistochemistry (IHC) and histochemistry is limited. Materials and methods To evaluate the diagnostic and prognostic utility of clinicopathological features, morphology, ancillary biomarkers, and reticular histochemistry in adrenocortical neoplasms. We examined 28 adrenocortical carcinomas (ACCs) and 50 adrenocortical adenomas (ACAs) obtained from pathology archives. Clinical data were retrieved from medical records. Two pathologists independently assessed hematoxylin and eosin-stained slides, employing modified Weiss criteria for all tumors and Lin-Weiss-Bisceglia criteria for oncocytic variants. Immunohistochemical markers (Calretinin, alpha-inhibin, MelanA, SF-1, Ki-67, PHH3, IGF-2, β-catenin, P53, CYP11B1, CYP11B2, MLH1, MSH2, MSH6, PMS2, EPCAM) and Gomori’s Silver histochemistry were applied. Statistical analysis utilized SPSS Statistics 26. Results ACCs exhibited larger tumor sizes (P

This study aimed to enhance the histopathological diagnosis of necrotic lymph node specimens. A chart review was conducted, revealing that the most common causes of lymph node necrosis were Kikuchi disease (33%), granulomatous inflammation (25%), metastasis (17%), and lymphomas (12%). Histological analysis of necrotic tissue in 333 specimens demonstrated significant differences between the four diseases. The necrotic tissue of Kikuchi disease was amorphous, and hypercellular, and exhibited karyorrhexis and congestion. Granulomatous inflammation presented amorphous necrotic tissue with a nodular-like pattern. Metastasis exhibited heterogeneous morphology that varied between cancer types. Lymphomas displayed extensive necrosis with ghost cells, congestion, and bubbles. Reticulin staining patterns also differed between diseases. Kikuchi disease and lymphomas exhibited preserved reticular fiber networks in the necrotic tissue, resembling the viable tissue. Granulomatous inflammation and metastasis showed disrupted reticular fiber networks in the necrotic tissue. Based on these findings, histological features and reticulin staining patterns can aid in diagnosing Kikuchi disease, granulomatous inflammation, metastasis, and lymphomas in necrotic lymph node specimens. [ABSTRACT FROM AUTHOR]

Background: Current diagnostic criteria of adrenocortical neoplasms are mostly based on morphology. The utility of immunohistochemistry (IHC) and histochemistry is limited. Materials and methods: To evaluate the diagnostic and prognostic utility of clinicopathological features, morphology, ancillary biomarkers, and reticular histochemistry in adrenocortical neoplasms. We examined 28 adrenocortical carcinomas (ACCs) and 50 adrenocortical adenomas (ACAs) obtained from pathology archives. Clinical data were retrieved from medical records. Two pathologists independently assessed hematoxylin and eosin-stained slides, employing modified Weiss criteria for all tumors and Lin-Weiss-Bisceglia criteria for oncocytic variants. Immunohistochemical markers (Calretinin, alpha-inhibin, MelanA, SF-1, Ki-67, PHH3, IGF-2, β-catenin, P53, CYP11B1, CYP11B2, MLH1, MSH2, MSH6, PMS2, EPCAM) and Gomori's Silver histochemistry were applied. Statistical analysis utilized SPSS Statistics 26. Results: ACCs exhibited larger tumor sizes (P<0.001) and symptomatic presentations (P = 0.031) compared to ACAs. Parameters of modified Weiss criteria and angioinvasion demonstrated diagnostic value for ACCs. Six immunohistochemical antibodies((MelanA, Ki-67, IGF-2, β-catenin, P53 and CYP11B1) and reticulin framework alterations showed diagnostic value. Notably, Ki-67 and reticulin staining were most recommended. Evident reticulin staining was frequently present in ACCs (P<0.001). Ki-67 was significantly higher in ACCs (P<0.001). Twenty-one conventional and seven oncocytic entities showed different necrosis frequencies. Symptoms and Ki-67 index ≥ 30% were prognostic for ACCs, correlating with shorter survival. Conclusions: This study emphasizes the diagnostic value of reticulin framework alterations and a high Ki-67 index. Markers such as CYP11B1, IGF2, P53, β-catenin and MelanA also contribute to the diagnosis of ACCs. Symptoms and Ki-67 index ≥ 30% predict shorter survival. These findings encourges the use of ancillary markers such as reticulin histochemistry and Ki-67 in the workup of evaluations of adrenocortical neoplasms. [ABSTRACT FROM AUTHOR]

Objectives: Tendon recovery after a surgical operation or traumatic injury is still one of the challenges of rehabilitation. Many recently formulated treatments have been designed to improve these procedures. This study aimed to evaluate the effects of recombinant basic fibroblast growth factor (bFGF) and cold atmospheric plasma (CAP) on calcaneus tendon healing and regeneration in rabbit models. Material and Methods: This study subdivided 40 mature male New Zealand white rabbits into four groups (n=10 in each). The defect was made under general conditions, and the wound was closed without treatment. The experimental groups included sham (without treatment), bFGF (operated bFGF in the injured area), CAP (used CAP in the injured area), and bFGF/CAP (used both CAP and bFGF) in the injured area. This study used trichrome and reticulin stains to evaluate collagen production and other tissue factors. Also, hydroxyproline levels were measured for better observation of collagen synthesis. Pathological evaluation of the defective tendon was performed on days 60 and 120 after surgery. Results: The improvement of new and parallel tendon formation was the best in the bFGF/CAP group at both times, especially 120 days after surgery. An increase in hydroxyproline levels was also seen on the sampling days. Conclusions: The experiment showed that bFGF/CAP combination significantly improved tendon remodeling in the injured areas.

Objectives: Tendon recovery after a surgical operation or traumatic injury is still one of the challenges of rehabilitation. Many recently formulated treatments have been designed to improve these procedures. This study aimed to evaluate the effects of recombinant basic fibroblast growth factor (bFGF) and cold atmospheric plasma (CAP) on calcaneus tendon healing and regeneration in rabbit models. Material and Methods: This study subdivided 40 mature male New Zealand white rabbits into four groups (n=10 in each). The defect was made under general conditions, and the wound was closed without treatment. The experimental groups included sham (without treatment), bFGF (operated bFGF in the injured area), CAP (used CAP in the injured area), and bFGF/CAP (used both CAP and bFGF) in the injured area. This study used trichrome and reticulin stains to evaluate collagen production and other tissue factors. Also, hydroxyproline levels were measured for better observation of collagen synthesis. Pathological evaluation of the defective tendon was performed on days 60 and 120 after surgery. Results: The improvement of new and parallel tendon formation was the best in the bFGF/CAP group at both times, especially 120 days after surgery. An increase in hydroxyproline levels was also seen on the sampling days. Conclusions: The experiment showed that bFGF/CAP combination significantly improved tendon remodeling in the injured areas. [ABSTRACT FROM AUTHOR]

Aims: Reticulin stain is used routinely in the histological evaluation of hepatocellular carcinoma (HCC). The goal of this study was to assess whether the histological reticulin proportionate area (RPA) in HCCs predicts tumour‐related outcomes. Methods and results : We developed and validated a supervised artificial intelligence (AI) model that utilises a cloud‐based, deep‐learning AI platform (Aiforia Technologies, Helsinki, Finland) to specifically recognise and quantify the reticulin framework in normal livers and HCCs using routine reticulin staining. We applied this reticulin AI model to a cohort of consecutive HCC cases from patients undergoing curative resection between 2005 and 2015. A total of 101 HCC resections were included (median age = 68 years, 64 males, median follow‐up time = 49.9 months). AI model RPA reduction of > 50% (compared to normal liver tissue) was predictive of metastasis [hazard ratio (HR) = 3.76, P = 0.004, disease‐free survival (DFS, HR = 2.48, P < 0.001) and overall survival (OS), HR = 2.80, P = 0.001]. In a Cox regression model, which included clinical and pathological variables, RPA decrease was an independent predictor of DFS and OS and the only independent predictor of metastasis. Similar results were found in the moderately differentiated HCC subgroup (WHO grade 2), in which reticulin quantitative analysis was an independent predictor of metastasis, DFS and OS. Conclusion : Our data indicate that decreased RPA is a strong predictor of various HCC‐related outcomes, including within the moderately differentiated subgroup. Reticulin, therefore, may represent a novel and important prognostic HCC marker, to be further explored and validated. [ABSTRACT FROM AUTHOR]

Background Low-vacuum scanning electron microscopy (LVSEM) enables the detailed three-dimensional imaging of archival tissues without special pretreatments. The clinical utility of LVSEM in the assessment of liver diseases has not yet been defined. So, we investigated the utility of LVSEM imaging in morphological assessments of normal and diseased liver tissues, with a focus on reticulin structures. Methods Formalin-fixed tissue samples of two normal livers and two hepatocellular carcinomas with background regenerative nodules/areas were stained with platinum blue stain or silver-impregnated using Watanabe's method and then comparatively observed under LVSEM. We also evaluated the applicability of LVSEM imaging of liver tissues to a quantitative analysis using a digital image analysis technique. Results Optimal high-resolution images of reticulin structures were obtained using 10-µm-thick silverimpregnated sections. Reticulin fibers were clearly observed to run dendritically around sinusoids in normal livers, and markedly increased in regenerative nodules/areas. Normal reticulin frameworks were lost in hepatocellular carcinoma, leaving a few fragments of reticulin fibers within tumors. Moreover, when a quantitative analysis was applied to these images, we successfully demonstrated a significantly higher reticulin fiber density in regenerative nodules/areas than in the normal liver (P < 0.05). Conclusion We not only obtained detailed threedimensional images of reticulin structures in various liver tissues by LVSEM combined with silver impregnation but also showed their applicability to a quantitative analysis. The method presented herein may be applied to future studies for the more accurate diagnosis and better classification/risk stratification of various liver diseases. [ABSTRACT FROM AUTHOR]

Background: Acinic cell carcinoma (AciCC) is the second most common pediatric malignant salivary gland tumor. However, there are limited pathology publications about this tumor in the pediatric population. Methods: We describe four pediatric AciCC cases diagnosed between 2000 and 2021 in our institute. Reticulin histochemistry plus immunohistochemistry for NR4A3 and DOG1 were performed on all cases. Results: Histologically, all four cases featured a tumor-associated lymphoid proliferation and collagenous stroma, in which two formed central scars. The tumors were predominantly solid, with a lobular pattern and variably sized dilated spaces, including one case with focal microcysts. High-grade transformation was not observed in any of our cases. Reticulin stain and immunohistochemistry for NR4A3 showed distinct features between AciCC and non-neoplastic salivary gland parenchyma. DOG1 immunohistochemistry confirmed the acinar origin of AciCC. Conclusions: Our study reveals that pediatric AciCCs often present with tumor-associated lymphoid proliferation (TALP) and sclerosis. Special stains such as reticulin histochemistry and NR4A3 immunohistochemistry are helpful to separate tumor from adjacent benign parenchyma. The ancillary study is helpful for the diagnosis of small specimens. Our study is limited by its low case number, but we hope that our results will promote more studies on this rare salivary gland tumor in the pediatric population. [ABSTRACT FROM AUTHOR]

Abstract Background This study evaluated histopathological characteristics of bone marrow (BM) of patients with immune thrombocytopenic purpura (ITP) and sought to find possible associations among them and clinical aspects. Method A retrospective study was carried out with 120 patients using BM clot and BM biopsy samples, including morphological (cytological and histological) re-evaluation, reticulin and hemosiderin analysis, and clinical outcome review of medical records. Immunohistochemistry (CD34 and CD117) was applied in a group of patients with increased reticulin, with the objective of exclusion Myelodysplastic syndrome cases Results Megakaryocytic hyperplasia was observed in 109 (90.8%) patients and increased reticulin was diagnosed in nine patients, five of them with a clinically unfavorable outcome (p = 0.042). The increase in reticulin graduation was associated with a higher risk of an unfavorable outcome. Conclusion Increased reticulin degree in BM of patients with ITP is associated with an unfavorable outcome in this study. It is rarely explored in the literature and may provide information that contributes to understanding the patient's outcomes.

Marine bio-sourced chitosan nanoparticles (CSNP) are antimicrobial and immunomodulatory agents beneficial for fish medicine. Herein, dietary CSNP was investigated for the amelioration of the systemic inflammatory responses of an induced fish model. One hundred and forty-four rainbow trout were assigned to one pathogen-free and non-supplemented group (negative control), and three challenged groups: non-supplemented (positive control), CSNP-preventive, and CSNP-therapeutic. After a feeding experiment extended for 21 days, the organosomatic indices (OSI) and molecular aspects were assessed. After a challenge experiment extended for further 28 days, CSNP-therapeutic intervention was assessed on fish survival and systemic inflammatory responses on pathology, histo-morphology, and molecular aspects. With CSNP administration, OSI nonsignificantly decreased and the relative expression of targeted inflammatory-mediator genes was significantly increased. The CSNP-therapeutic fish showed an RPS of 80% as compared to the positive control group, and CSNP-therapeutic administration retained the highest gene expression augmentation up to 28 days after the challenge. Notably, the splenic reticulin fibers framework of the CSNP-therapeutic group retained the highest integrity among the groups during the infection. After recovery, reticulin fibers density in the CSNP-therapeutic samples was significantly higher than in the negative control group, which indicates high innate immunity. Thus, CSNP showed promising biotherapeutic features enhancing fish resistance against infections. [ABSTRACT FROM AUTHOR]

Well-differentiated hepatocellular mass-lesions in non-cirrhotic livers have a differential diagnosis of focal nodular hyperplasia, regenerative hepatic pseudotumors, hepatic adenoma, hepatocellular carcinoma, and fibrolamellar carcinoma. Despite significant advances in characterizing these pseudotumors and tumors, they remain a diagnostic challenge, especially on needle biopsy. This review focuses on a systematic diagnostic approach, one that allows confident diagnosis of these lesions. [ABSTRACT FROM AUTHOR]

Nodular regenerative hyperplasia (NRH) can manifest as alternating parenchymal compression/expansion on hematoxylin and eosin (H&E) staining and as reticulin collapse/nodularity on reticulin staining. Histologic diagnosis can be challenging, especially when there is mild disease and on limited biopsy samples. We reviewed clinical and histologic parameters in a large series of NRH. We identified 60 liver specimens convincingly showing changes of NRH and reviewed them for clinical (age, sex, symptoms, lab values, portal hypertension [PHTN], NRH etiology) and histologic (inflammation, sinusoidal dilation, cholestasis, architectural change, portal vascular abnormalities, degree of changes on reticulin) parameters. The cases came from 28 women and 32 men (median age: 54 years). Most (55, 92%) were biopsies. Thirty patients were symptomatic. Forty-five cases showed mild NRH changes on reticulin; 24 of these (53%) showed them on H&E as well. Fifteen demonstrated well-developed changes on reticulin, which were always seen on H&E as well. Sinusoidal dilation was commonly observed in both of these subgroups (88% overall). Portal vascular abnormalities were seen in 33%. Well-developed NRH was diffuse more often than mild NRH (53% vs. 4%, P < 0.0001). Twenty-nine patients had clinically confirmed or likely PHTN. Of these, 21 showed mild and 8 showed well-developed NRH changes; only 3 had concomitant advanced fibrosis. Chemotherapy was the most frequent known cause of NRH; 30 patients lacked any definite etiology. NRH can be difficult to diagnose on biopsy, particularly since mild changes may be visible on reticulin but not H&E; even these patients can have PHTN. Additionally, NRH is often idiopathic, potentially lowering clinical and pathologic suspicion. Pathologists should have a low threshold for ordering reticulin stains, especially when a patient is known to have PHTN. Sinusoidal dilation, while nonspecific, commonly accompanies NRH. [ABSTRACT FROM AUTHOR]

The myeloproliferative neoplasms (MPN) are a group of clonal myeloid proliferations characterised by varying combinations of increased circulating red cells, granulocytes and platelets caused by excess proliferation of haemopoietic precursors in bone marrow with retained cellular maturation. These disorders typically pursue an indolent course requiring management of the consequences of the increased circulating elements (predominantly effects of thrombosis of haemorrhage in different body organs). Patients have complex symptoms, including fatigue, which are not yet fully explained. The MPN carry varying risks of progression to an acute phase characterised by increasing bone marrow and circulating blasts cells, and/or to fibrosis characterised by falling peripheral cell counts and increasing splenomegaly. Megakaryocyte morphology in BMT samples provides essential clues for diagnosis and subtyping in MPN; high quality and consistent reticulin staining for accurate assessment is also key. [ABSTRACT FROM AUTHOR]

Adrenocortical carcinomas (ACC) are aggressive tumors with a poor prognosis. Histological scores are advised for the diagnosis, however, there are borderline cases that may be misjudged as adrenocortical adenomas (ACA). The three main scores used are: Weiss Modified System (WMS), Reticulin Algorithm (RA), and Helsinki Score (HS). We intend to compare the accuracy of the three scores in ACC diagnosis and to identify predictive factors of overall survival (OS). Retrospective study (2004–2016) at Centro Hospitalar e Universitário de Coimbra of the adrenal tumors, classified as ACC or ACA, with a history of posterior tumor relapse/metastases, without lesions in the contralateral adrenal gland: 13F and 6M, with a median age of 51 ± 12.41 years. Nodules' median size was 9.20 ± 6.2 cm. Patients had a median OS of 52 ± 18.6 months, with 57.9% and 46.3%, at 3 and 5 years. Seven patients had local recurrence and nine had metastases. Thirteen cases were in stage II. The WMS and the HS allowed a diagnosis of ACC in 15 cases and the RA defined ACC in 17 cases. All cases had, at least, focal disruption of the reticulin framework. More than 5 mitosis/50 HPF was associated with worse OS: 49.67 ± 21.43 versus 108.86 ± 14.02 months (p = 0.026). In patients with stage II, tumor size ⩾10 cm was associated with worse OS: 19.25 ± 7.15 versus 96.11 ± 16.7 months (p = 0.007), confirmed by multivariate analysis (p = 0.031). The correct diagnosis of ACC is a pathologist responsibility. The RA seems the most accurate. Any loss of the reticulin framework should raise awareness for malignancy. In patients on stage II, a size ⩾10 cm is a predictor of worse prognosis. [ABSTRACT FROM AUTHOR]

Immune thrombocytopenic purpura is a clinical syndrome of thrombocytopenia that manifests as a bleeding tendency, typical skin rashes, easy bruising, or extravasation of blood from the capillaries. Defects in the thrombopoietin-receptor (TPOR)/myeloproliferative leukaemia virus/JAK2 axis leads to haematological diseases such as thrombocytopenia or pancytopenia through the inhibition of the megakaryopoiesis process. Thrombopoietin-receptor agonists (TPORA), such as eltrombopag, increase platelet count by stimulating the TPOR. Bone marrow (BM) fibrosis has been reported in patients receiving TPORA. Myelofibrosis (MF) may be induced by mutations in JAK2, CALR, and MPL genes. This review gives an insight on MF as a serious side effect induced by eltrombopag. This review enriches the evidence of MF induced by eltrombopag after long-term administration ranging from 6 months to 7 years. MF is mostly spontaneous and decreases after discontinuation of medication; however, in a few cases it becomes persistent. This major issue should be treated with high concern. The authors recommend that any patient on eltrombopag treatment should be under vigilant observation and closely monitored for any sign of MF by clinical manifestation and any abnormal result from peripheral blood smear examination, and should additionally undergo BM biopsy for confirmation and detection of the severity of MF. The authors recommend discontinuing the medication if this side effect occurs. The authors also recommend to conduct larger studies for longer periods using serial BM before, and periodically after, eltrombopag treatment to evaluate the characteristics of this adverse effect.

Marine bio-sourced chitosan nanoparticles (CSNP) are antimicrobial and immunomodulatory agents beneficial for fish medicine. Herein, dietary CSNP was investigated for the amelioration of the systemic inflammatory responses of an induced fish model. One hundred and forty-four rainbow trout were assigned to one pathogen-free and non-supplemented group (negative control), and three challenged groups: non-supplemented (positive control), CSNP-preventive, and CSNP-therapeutic. After a feeding experiment extended for 21 days, the organosomatic indices (OSI) and molecular aspects were assessed. After a challenge experiment extended for further 28 days, CSNP-therapeutic intervention was assessed on fish survival and systemic inflammatory responses on pathology, histo-morphology, and molecular aspects. With CSNP administration, OSI nonsignificantly decreased and the relative expression of targeted inflammatory-mediator genes was significantly increased. The CSNP-therapeutic fish showed an RPS of 80% as compared to the positive control group, and CSNP-therapeutic administration retained the highest gene expression augmentation up to 28 days after the challenge. Notably, the splenic reticulin fibers framework of the CSNP-therapeutic group retained the highest integrity among the groups during the infection. After recovery, reticulin fibers density in the CSNP-therapeutic samples was significantly higher than in the negative control group, which indicates high innate immunity. Thus, CSNP showed promising biotherapeutic features enhancing fish resistance against infections.

The role of bone marrow (BM) fibrosis on outcomes of children with acute lymphoblastic leukemia (ALL) has been described with inconsistent results. In adults, there is no information regarding its significance. The aim of this study was to describe the prognostic impact of BM fibrosis in this group of patients. We included 88 biopsies of 44 adult patients. Reticulin and Masson trichrome stains were performed. Fibrosis was graded by modified Bauermeister scale and volume of reticulin/collagen fibers, both methods had good correlation. Survival analyses were performed regarding (1) the presence or not of significant fibrosis at diagnosis, (2) the reduction or not of fibrosis post-treatment, and (3) the amount of fibrosis at diagnosis combined with the depth of the reduction post-treatment. Sixty-six percent of the patients had significant fibrosis at diagnosis (Bauermeister ≥ grade 2) and 45% achieved a significant reduction (≥ 50% volume of reticulin/collagen fibers) post-treatment. The presence of fibrosis at diagnosis had no clear impact on outcomes; however, a significant reduction of the fibrosis post-treatment in patients with standard-risk ALL was correlated with longer RFS (19.1 months vs 10.6 months, p =.022) and OS (54.4 months vs 16.4 months, p =.033). Patients who had fibrosis at diagnosis combined with a deep reduction post-treatment had a better RFS and OS compared with those who did not have fibrosis at diagnosis regardless of its reduction or those who did not achieve a deep reduction. To our knowledge, this is the first study to describe an impact of BM fibrosis reduction post-treatment in adult patients with ALL. [ABSTRACT FROM AUTHOR]

Introduction: Reticulin staining has been suggested as an inexpensive tool in the differential diagnosis of melanoma versus benign nevi. In the present study, reticulin immunostaining patterns in malignant melanomas, benign intradermal nevi, and blue nevi were observed. The concordance in evaluation of the pattern between observers was also done. Materials and Methods: A retrospective search was performed in the computer database of the Ackerman Academy of Dermatopathology for “melanoma,” “melanocytic nevus,” and “blue nevus”. Fifty-six melanomas (30 of nodular subtype and 26 of superficial spreading subtype), 54 benign compound nevi, and 27 blue nevi were selected for the study. Patterns of reticulin staining in the dermis and the basement membrane in these melanocytic lesions were evaluated and the concordance between the two groups of authors was assessed. Statistical evaluation was performed with the Statistica® 10 program, Tulsa, OK. Concordance of the pattern evaluation was evaluated using Cohen's kappa coefficient. Results: Melanomas show a variable basement membrane pattern some of which show flat, thin and smooth pattern. Benign nevi almost never showed this flat pattern at the basement membrane zone. In the dermis, melanomas showed reticulin fibers surrounding groups of melanocytic cells while nevi predominantly had reticulin fibers around individual cells. There was greater agreement in evaluating the dermal component compared to the basement membrane pattern. Conclusion: The dermal reticulin staining pattern may be of some value in the diagnosis of melanocytic lesions, but poor concordance in evaluation of the basement membrane zone pattern limits its usefulness.

Diagnosis of benign and purely localized malignant adrenocortical lesions is still a complex issue. Moreover, histology-based diagnosis may suffer of a moment of subjectivity due to inter- and intra-individual variations. The aim of the present study was to assess, by computerized morphometry, the morphological features in benign and malignant adrenocortical neoplasms. Eleven adrenocortical adenomas (ACA) were compared with 18 adrenocortical cancers (ACC). All specimens were stained with H&E, cellular proliferation marker Ki-67 and reticulin. We generated a morphometric model based on the analysis of volume fractions occupied by Ki-67 positive and negative cells (nuclei and cytoplasm), vascular and inflammatory compartment; we also analyzed the surface fraction occupied by reticulin. We compared the quantitative data of Ki-67 obtained by morphometry with the quantification resulting from pathologist’s visual reading. The volume fraction of Ki-67 positive cells in ACCs was higher than in ACAs. The volume fraction of nuclei in unit volume and the nuclear/cytoplasmic ratio in both Ki-67 negative cells and Ki-67 positive cells were prominent in ACCs. The surface fraction of reticulin was considerably lower in ACCs. Our computerized morphometric model is simple, reproducible and can be used by the pathologist in the histological workup of adrenocortical tumors to achieve precise and reader-independent quantification of several morphological characteristics of adrenocortical tumors. [ABSTRACT FROM AUTHOR]

Background: The long-term effects of eltrombopag on bone marrow (BM) reticulin and/or collagen deposition in previously treated adults with chronic immune thrombocytopenia (ITP) were assessed. Methods: Three BM biopsies were collected at baseline and after 1 and 2 years of eltrombopag treatment. Specimens were centrally processed, stained for reticulin and collagen, independently reviewed by 2 hematopathologists, and rated according to the European Consensus 0-3 scale of marrow fibrosis (MF). Results: Of 162 patients enrolled, 93 completed all 3 protocol-specified BM biopsies. All patients with a baseline assessment were negative for collagen. Of 159 patients assessed at baseline, 150 (94%) had normal reticulin (MF-0) and 9 (6%) had minimally increased reticulin (MF-1). After 2 years, 83/93 patients (89%) with BM biopsies had MF-0, 10 (11%) had MF-1, and none had MF-2 or MF-3. Five out of 127 patients (4%) at 1 year and 1 out of 93 (1%) at 2 years had collagen deposition. None of the patients had clinical symptoms typical of BM dysfunction or abnormalities of clinical concern based on white blood cell count or peripheral blood smear. Conclusion: For most patients with chronic ITP, eltrombopag is not associated with clinically relevant increases in BM reticulin or collagen formation. [ABSTRACT FROM AUTHOR]

Purpose: To compare histologically transected fila from pediatric patients with tethered cord syndrome (TCS), with and without a low conus, with controls, focusing on collagenous and elastic tissue. Methods: Thirty fila from patients with TCS, including 5 where minimal cautery was used prior to filum section, were compared with fila from 27 pediatric cadavers without TCS (controls). Sections of fila were stained with H&E, Masson trichrome and Verhoeff von Gieson elastic stains, and 7 with Gordon and Sweet's reticulin stain. Results: Fila from controls showed loose fibrous connective tissue (FCT) with thin and evenly dispersed elastic fibers (EFs). Reticulin fibers (RFs) were seen in blood vessel walls and nerve twigs. Fat was identified microscopically in 2 fila. All fila from patients with TCS had dense FCT. The EFs were in normal numbers in 17, and focally or diffusely decreased in 13. All 25 patients where the fila were cauterized during resection had thick and coiled EFs. Coiling was not seen when minimal cautery was applied. RFs were seen in blood vessel walls and nerve twigs. Fat was identified in 19 patients. Findings were similar, whether the conus termination was normal or low. Conclusion: The fila of all patients with TCS, whether or not the conus was low, showed abnormal FCT. EFs were decreased in 48 % of patients; however, there were thick and coiled EFs in all patients. Coiling of EFs, initially thought to be an abnormality in patients, is considered most likely to be a result of cautery (i.e., artifactual/iatrogenic coiling). [ABSTRACT FROM AUTHOR]

The effects of romiplostim on bone marrow morphology were evaluated in adults with immune thrombocytopenia (ITP). Patients with platelet counts <50 × 10(9)/L, ≥1 prior ITP therapies, and no collagen at baseline received weekly subcutaneous romiplostim starting at 1 μg/kg, adjusted to maintain platelet counts between 50 and 200 × 10(9)/L. Biopsies were scheduled after 1, 2, or 3 years of romiplostim (cohorts 1, 2, and 3, respectively). Irrespective of scheduled time, biopsies were performed earlier if patients discontinued or failed to achieve/maintain a response to romiplostim. Reticulin (silver stain) and collagen (trichrome stain) were graded by two hematopathologists using the modified Bauermeister scale (0-4). Of 169 patients, 131 had evaluable biopsies; 9/131 (6.9 %) had increases of ≥2 grades on the modified Bauermeister scale (cohort 1: 0/34; cohort 2: 2/39; cohort 3: 7/58), including two with collagen. Three of the nine patients had follow-up biopsies, including one patient with collagen; changes were reversible after romiplostim discontinuation. Of the nine patients, one had neutropenia detected by laboratory test and two had adverse events of anemia, both non-serious and not treatment-related. By actual exposure (as some biopsies did not occur as scheduled), the number of patients with grade increases ≥2 were year 1: 3/41, year 2: 1/38, year 3: 5/52. Twenty-four patients sustained platelet counts ≥50 × 10(9)/L for ≥6 months with no ITP medications after discontinuing romiplostim, i.e., they entered clinical remission of their ITP. In conclusion, in patients with ITP receiving romiplostim, bone marrow changes were observed in a small proportion of patients.ClinicalTrials.gov identifier: NCT#00907478. [ABSTRACT FROM AUTHOR]

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Background: Adrenocortical carcinoma is a rare cancer, with an incidence in the literature of 0.5 to 2 cases per million population per year. Adult adrenocortical carcinoma has a poor prognosis, underscoring the importance of identifying diagnostic and prognostic markers. Methods: We searched our laboratory database for all cases in the past 15 years with a diagnosis of adrenocortical carcinoma. The original slides were then reviewed for their histopathological features. A representative paraffin block was subjected to further immunohistochemical staining for Ki-67, inhibin, steroidogenic factor-1 (SF-1), p53, and ?-catenin. These slides were scored by the study pathologist who was blinded to all clinicopathological data. In addition, a comprehensive review of the relevant English literature in the past 15 years was conducted. Results: Eight cases were identified, including two adrenal sarcomatoid carcinomas. Seven of the eight cases had a disrupted reticulin network. Six of the eight tumors had >10% Ki-67 expression. Five of the eight tumors had >10% p53 expression. Positive inhibin immunohistochemical staining was seen in three of the eight tumors, and positive SF-1 staining was seen in five of the seven stained tumors. Abnormal ?-catenin intracellular accumulation was noted in four of the eight tumors. The two tumors in our series with sarcomatoid histology did not stain positively for SF-1 or inhibin. Conclusions: Eight cases of adrenocortical carcinoma, including two with sarcomatoid features are presented. The two sarcomatoid adrenocortical carcinomas in our series did not stain for SF-1 which suggests a possible de novo pathway of tumorigenesis for this rare variant. The reticulin staining method was a useful tool for rapid differentiation of adrenocortical adenomas and carcinomas. Diffuse p53 staining showed a trend for positive correlation with increased Ki-67 expression. Inhibin staining was inconsistently expressed in our cases of adrenocortical carcinoma. In conclusion, as adrenocortical carcinoma is a rare disease, we recommend future multicenter studies with appropriate sample sizes to further evaluate the efficacy of these diagnostic and prognostic markers. [ABSTRACT FROM AUTHOR]

O diagnóstico acurado da doença celíaca é muito importante porque os pacientes devem aderir a uma dieta sem glúten por toda a vida e diante do maior risco de complicações, como as neoplasias intestinais, que poderá advir do não cumprimento rigoroso da dieta. Nesta revisão são apresentados os novos conceitos referentes às formas de apresentação da doença (ativa, silenciosa, latente e potencial) e sua associação com outras enfermidades e são focalizados principalmente o valor e a eficácia da determinação dos anticorpos séricos antigliadina e dos autoanticorpos anti-reticulina, antiendomísio e antitransglutaminase tecidual, no auxílio ao diagnóstico e seguimento da doença celíaca.Accurate diagnosis of celiac disease is important because patients are advised to adhere to a strict gluten-free diet for life. This management is critical to avoid disease complications such as malignancies. In this review the new terminology for the disease clinical features (active, silent, latent and potential celiac disease) and the disease association with other conditions are commented. The value and efficacy of the assessment of serum antigliadin antibodies and of antireticulin, antiendomysial and tissue transglutaminase autoantibodies in the diagnosis and follow-up of the celiac disease are particularly evaluated.

Copyright of Revista Española de Patología is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: Some investigators have suggested that medulloblastomas can be distinguished from other cerebellar neoplasms by demonstrating 'restricted diffusion' on the Apparent Diffusion Coefficient (ADC) map obtained from diffusion-weighted imaging (DWI) sequences on magnetic resonance imaging. Previous authors have postulated that this observed restricted diffusion is a reflection of very high cell density. There has been a tendency to assert that pediatric medulloblastoma uniformly demonstrates restricted diffusion on DWI. However, our clinical observation has been that there are pediatric medulloblastomas that exhibit normal or even increased diffusion on DWI. The current study was undertaken primarily to determine whether restricted diffusion is uniformly present in pediatric medulloblastoma and secondly to look for pathological features that might distinguish medulloblastomas with and without restricted diffusion. Methods: The DWI characteristics of pathologically confirmed medulloblastomas diagnosed at our institution were retrospectively reviewed. The ADC was obtained in two non-overlapping, solid, non-hemorrhagic, non-necrotic regions of tumor and averaged. An ADC below 1 × 10 mm/s was considered to represent restricted diffusion. A detailed pathologic review of each tumor was conducted. Results: Ten cases of medulloblastoma were reviewed, of which two demonstrated average ADCs above 1 × 10 mm/s (1.223 and 1.169 × 10 mm/s, respectively), indicating no restricted diffusion. Pathologic review revealed that both of these non-restricting cases displayed a lack of reticulin deposition by light microscopy. Conclusion: DWI does not appear to be an entirely reliable means of distinguishing medulloblastomas from other cerebellar neoplasms. Histologically, restricted diffusion in medulloblastomas may be related to reticulin deposition. [ABSTRACT FROM AUTHOR]

Primary extra nodal lymphomas (EN-NHL) are different from primary nodal non-Hodgkin's lymphoma (N-NHL) and are comparatively less common. Hemogram findings and bone marrow involvement is less studied and very few reports are available in the literature. The present study is a retrospective analysis of bone marrow samples evaluated for staging of non-Hodgkin's lymphoma. The age, sex distribution, clinical features, and site of presentation, hemogram findings, pattern of bone marrow involvement and grade of reticulin fibrosis was noted. These findings were compared with the type of non-Hodgkin's lymphoma and prognostic information was determined. A total of 647 cases of NHL, which underwent bone marrow examination for staging, over a seven year period, were retrieved and analyzed for all hematological parameters. Prevalence of EN-NHL was 23.5% (152/647), while nodal NHL comprised 76.5% (495/647) of all NHL cases. 90.1% (137/152) cases of EN-NHL were adult patients, out of which 15.3% (21/137) cases showed bone marrow infiltration as compared to 89% (441/495) adult primary nodal NHL cases, of which 39% (175/441) showed bone marrow infiltration. 9.9% (15/152) cases of EN-NHL were pediatric patients, out of which 40% (6/15) showed bone marrow infiltration, while 10.9% (54/495) of nodal NHL cases were pediatric, of which 20.3% (11/54) showed bone marrow infiltration. Hemogram findings were not found useful in predicting bone marrow infiltration in both nodal as well as EN-NHL. 100% (6/6) of pediatric patients had high grade lymphoma as compared to 48% (9/21) of adult patients, showing bone marrow infiltration in EN-NHL group. Reticulin fibrosis also did not reveal relation with grading of NHL. Prognostically EN-NHL of stomach and central nervous system were found to be better than EN-NHL of other sites, as none of these cases showed bone marrow infiltration. EN-NHL can involve various sites and the prognosis depends upon the sites of disease as well as the type of NHL. Moreover, pediatric EN-NHL cases are likely to have poorer prognosis, due to increased risk of bone marrow involvement as compared to their counterparts having primary nodal NHL. Bone marrow infiltration at times cannot be assessed reliably from hemogram findings only and a bone marrow biopsy for staging is mandatory. [ABSTRACT FROM AUTHOR]

The Philadelphia chromosome-negative (Ph-) chronic myeloproliferative neoplasms include the three well-known clinical entities polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Over time, patients with ET and PV may develop myelofibrosis (MF), and all three entities carry a risk of transformation into acute myeloid leukemia (AML). In a population-based survey during 1983-1999, we studied a total of 358 patients who were diagnosed with ET and PV in the city of Gothenburg, Sweden. At the time of diagnosis, evaluable bone marrow biopsy material was available from 280 of these patients. The current work was aimed at investigating the impact of peripheral blood counts, spleen size, and bone marrow biopsy findings at diagnosis on long-term survival and the risk of development of AML or MF in this well-defined unselected population. The variables evaluated were venous blood hemoglobin concentration, packed cell volume, white blood cell count, platelet count, and splenic enlargement; as to bone marrow biopsies, interest was focused on reticulin content, focal or generalized collagen formation, bone marrow cellularity, and megakaryocyte profile number. Over the median observation time of 15 yr, the patients with ET did not demonstrate any significant difference as to survival compared to the normal Swedish population (hazard ratio, 1.23; 95% confidence interval, 0.97-1.51; p = 0.089). The patients with PV, on the other hand, had a significantly shorter survival compared to general population (hazard ratio, 1.66; 95% confidence interval, 1.38-1.99; p < 0.001). A lower hemoglobin concentration at diagnosis of ET predicted poorer survival ( p = 0.0281), whereas patients with PV with splenic enlargement at diagnosis had a shorter survival ( p = 0.037). In the patients with ET, the risk of transformation to either MF or AML was significantly associated with low hemoglobin concentration and high white cell count at diagnosis ( p = 0.0037 and 0.0306, respectively). An increased reticulin content and hypercellularity in the bone marrow at diagnosis were also independent risk factors ( p = 0.0359 and 0.0103, respectively). The risk of transformation in patients with PV was significantly associated with splenic enlargement and increase in bone marrow reticulin content ( p = 0.0028 and 0.0164, respectively). [ABSTRACT FROM AUTHOR]

Myelofibrosis is commonly seen in patients with chronic myeloproliferative diseases and sometimes in myelodysplastic syndrome, acute leukaemia and lymphoproliferative diseases. The fibrotic process is evaluated by grading the amount of collagen deposited in the bone marrow interstitium. The established method to evaluate bone marrow fibrosis is staining for reticulin to visualise the collagen fibres. However, the extra cellular matrix does not only contain collagens but also other components, e.g. glycosaminoglycans of which hyaluronan is the most abundant. Hyaluronan is important for structural and cellular functions. Earlier studies have shown that there is a positive correlation between hyaluronan and reticulin staining in healthy volunteers and in patients with de novo acute myeloid leukaemia. In this study bone marrow biopsies from 43 patients with a malignant disease involving the bone marrow were compared with 18 patients with a malignant disease not involving the bone marrow. The intensity of hyaluronan grading was significantly higher in the patients with disease involving the bone marrow compared to the healthy controls but not compared to the patients without disease involving the bone marrow. The staining intensity of reticulin in the bone marrow was significantly higher in the patients with disease involving the bone marrow, compared to those without disease involving the bone marrow and to the controls. In all patients and the controls there was a correlation between hyaluronan and reticulin. [ABSTRACT FROM AUTHOR]

Introduction: Reticulin staining has been suggested as an inexpensive tool in the differential diagnosis of melanoma versus benign nevi. In the present study, reticulin immunostaining patterns in malignant melanomas, benign intradermal nevi, and blue nevi were observed. The concordance in evaluation of the pattern between observers was also done. Materials and Methods: A retrospective search was performed in the computer database of the Ackerman Academy of Dermatopathology for "melanoma," "melanocytic nevus," and "blue nevus". Fifty-six melanomas (30 of nodular subtype and 26 of superficial spreading subtype), 54 benign compound nevi, and 27 blue nevi were selected for the study. Patterns of reticulin staining in the dermis and the basement membrane in these melanocytic lesions were evaluated and the concordance between the two groups of authors was assessed. Statistical evaluation was performed with the Statistica® 10 program, Tulsa, OK. Concordance of the pattern evaluation was evaluated using Cohen's kappa coefficient. Results: Melanomas show a variable basement membrane pattern some of which show flat, thin and smooth pattern. Benign nevi almost never showed this flat pattern at the basement membrane zone. In the dermis, melanomas showed reticulin fibers surrounding groups of melanocytic cells while nevi predominantly had reticulin fibers around individual cells. There was greater agreement in evaluating the dermal component compared to the basement membrane pattern. Conclusion: The dermal reticulin staining pattern may be of some value in the diagnosis of melanocytic lesions, but poor concordance in evaluation of the basement membrane zone pattern limits its usefulness. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a sexually dimorphic, autoimmune inflammatory disorder affecting the joints. Joint disability in RA results primarily from loss of matrix components (collagen and glycosoaminoglycan) in the cartilage and synovium. This study was carried out to understand the effect of physiological levels of testosterone, estrogen, and progesterone on oxidative stress-induced changes in matrix composition in rat synovium in arthritis. Arthritis induction in castrated and ovariectomized rats resulted in enhanced oxidative stress and this was assessed by lipid peroxidation levels and depletion of antioxidants. This, in turn, led to significantly ( p < 0.01) increased levels of TNF-α and matrix metalloproteinase-2 (MMP-2), subsequently resulting in loss of collagen, elastin, and glycosoaminoglycan (GAG) and disorganization of reticulin as evidenced by biochemical quantitation and also by staining for collagen, reticulin, and elastin. Treatment with physiological doses of dihydrotestosterone (25 mg topically) and estrogen (5 μg/0.1 ml subcutaneously) restored the antioxidant levels significantly ( p < 0.05) and reduced the levels of TNF-α and MMP-2, with estrogen exhibiting a higher potency. This, in turn, attenuated the damage to reticulin organization as well as the loss of collagen and GAG in the articular tissues. However, elastin loss could not be attenuated by either treatment. Progesterone (2 mg/0.1 ml subcutaneously) was not shown to have any significance in disease modification, and on the contrary, it inhibited the protective effects of estrogen. However, progesterone contributed to increased collagen levels in the tissues. [ABSTRACT FROM AUTHOR]

Liver fibrosis, the response to chronic liver injury, results from the activation of mesenchymal cells to fibrogenic myofibroblasts. We have recently shown that two key myofibroblast precursor populations, hepatic stellate cells and portal fibroblasts, undergo activation in culture in response to increasing substrate stiffness. We therefore hypothesized that alterations in liver stiffness precede myofibroblast activation and fibrosis in vivo as well. To test this hypothesis, we induced fibrosis in rats by twice weekly injections of carbon tetrachloride (CCL4) and then killed the animals at various time points ranging from 3 to 70 days after the initiation of injury. The shear storage modulus of the whole liver was measured on fresh tissue; fixed and frozen tissue from the same livers was used to quantify fibrosis. We observed that liver stiffness increased immediately and continued to increase, leveling out by day 28. Fibrosis, measured histologically by trichrome staining as well as by quantitative sirius red staining, increased with time, although these increases were delayed relative to changes in stiffness. There was no direct correlation between stiffness and fibrosis at early or late time points. Treatment of a second cohort of rats with the lysyl oxidase inhibitor, β-aminopropionitrile (BAPN), partially prevented early increases in liver stiffness. We concluded that increases in liver stiffness precede fibrosis and potentially myofibroblast activation. Liver stiffness appears to result from matrix cross-linking and possibly other unknown variables in addition to matrix quantity. We suggest that increased liver stiffness may play an important role in initiating the early stages of fibrosis. [ABSTRACT FROM AUTHOR]

In bone marrow biopsies, stromal structural fibres are detected by reticulin and trichrome stains, routine stains performed on bone marrow biopsy specimens in diagnostic laboratories. Increased reticulin staining ( reticulin fibrosis) is associated with many benign and malignant conditions while increased trichrome staining ( collagen fibrosis) is particularly prominent in late stages of severe myeloproliferative diseases or following tumour metastasis to the bone marrow. Recent evidence has shown that the amount of bone marrow reticulin staining often exhibits no correlation to disease severity, while the presence of type 1 collagen, as detected by trichrome staining, is often associated with more severe disease and a poorer prognosis. It was originally thought that increases in bone marrow stromal fibres themselves contributed to the haematopoietic abnormalities seen in certain diseases, but recent studies suggest that these increases are a result of underlying cellular abnormalities rather than a cause. A growing body of evidence suggests that increased deposition of bone marrow stromal fibres is mediated by transforming growth factor- β and other factors elaborated by megakaryocytes, but it is likely that other cells, cytokines and growth factors are also involved. This suggests new avenues for investigation into the pathogenesis of various disorders associated with increased bone marrow stromal fibres. [ABSTRACT FROM AUTHOR]

Background: Focal zones of hepatic necrosis alternating with nodular regeneration in severe, acute to subacute hepatitis can be difficult to differentiate histologically from established cirrhosis, and diagnostic errors can result in incorrect patient management. Thus, an easily applicable, well-defined histologic method for differentiating these two lesions would be useful. Methods: We examined trichrome (TRI), reticulin (RETIC), Verhoeff's elastic (VE), and orcein (ORC) stains on 13 cases of hepatic necrosis with regenerative nodules and 10 cases of end-stage cirrhosis to evaluate their utility for this problem. Results: Zones of recent necrosis in all severe hepatitis cases stained paler blue or pink, respectively, with TRI and VE than the established scar in cirrhosis or residual normal portal zones/central vein walls. With VE and ORC, elastic fibres were not seen in the necrotic zones of severe hepatitis, but were present in all cirrhotic livers. RETIC outlined the residual cell plate architecture in necrotic areas but had indistinct staining in fibrotic areas. The combination of the RETIC, TRI and ORC distinguished hepatic necrosis with regenerative nodules from nodules in the scar of established cirrhosis in 100% of the cases examined. Conclusion: We conclude that this trio of special stains can be helpful adjuncts for this diagnostic problem. [ABSTRACT FROM AUTHOR]

The object of this study was to analyze the hepatic effects of the herbicide Glyphosate-Biocarb® (as commercialized in Brazil) in Wistar rats. Animals were treated orally with water or 4.87, 48.7, or 487 mg/kg of glyphosate each 2 days, during 75 days. Sub-chronic treatment of animals starting from the lowest dose of glyphosate induced the leakage of hepatic intracellular enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), suggesting irreversible damage in hepatocytes. We observed the increase of Kupffer cells in hepatic sinusoid of glyphosate-treated animals. This was followed by large deposition of reticulin fibers, composed mainly of collagen type III. We may conclude that Glyphosate-Biocarb® may induce hepatic histological changes as well as AST and ALT leaking from liver to serum in experimental models. [Copyright &y& Elsevier]

Unlabelled: The aim of this study was to evaluate whether coeliac disease affects growth, glycaemic control, and general well-being of children and adolescents with type I diabetes. Eighteen subjects were found to have coeliac disease by a screening program. Gastrointestinal symptoms, changes in growth and the levels of glycated haemoglobin (GHbA1) were analysed, as well as subjective well-being before and after diagnosis of coeliac disease. Overt gastrointestinal symptoms and deterioration of growth prior to disclosure of coeliac disease were seen only in one patient who had both of these conditions. Retrospectively, most subjects reported mild gastrointestinal complaints, which resolved on a gluten-free diet. Introduction of a gluten-free diet did not have any positive effect on glycaemic control, but was associated with an increase in weight-for-height (from 4.3+/-18.1 to 8.2+/-15.4% deviation from population median, p = 0.02). This increase in weight-for-height was inversely correlated with changes in GHbA1 (r = -0.574, p = 0.02).Conclusion: Coeliac disease is rarely associated with signs of malabsorption in children and adolescents with type I diabetes. Introduction of a gluten-free diet may be associated with excess weight gain. We recommend intensified follow-up for these subjects. [ABSTRACT FROM AUTHOR]

The function of jejunal intraepithelial γδ+ T cells is obscure, but they are commonly implicated as playing a role in inflammatory and autoimmune conditions. In coeliac disease (CoD), there are controversial reports as to gluten dependency of these cells. We have now studied the small bowel mucosal intraepithelial T cell densities, and the ratios of γδ+ to CD3+ T cells and γδ+ to αβ+ T cells during early disease development and on a gluten-free diet. Nine children initially excluded for CoD were followed up and rebiopsy after 0.8–4.5 years showed mucosal deterioration. Further, 21 biopsy specimens from newly diagnosed CoD patients were studied, together with 20 specimens taken from children on a gluten-free diet. During CoD development the density of γδ+ and αβ+ T cells as well as the ratios of γδ+ to CD3+ T cells and γδ+ to αβ+ T cells increased. In the latent stage of CoD when the small bowel mucosal architecture was still normal, two children had clearly normal densities of γδ+ (< 2.5 cells/100 epithelial cells) and αβ+ (< 25.0 cells/100 epithelial cells) T cells, and low ratios as well. In patients with newly diagnosed CoD the densities decreased significantly on a long-term gluten-free diet. We conclude that the density of intraepithelial γδ+ T cells as well as αβ+ T cells in CoD is gluten-dependent. CoD can develop in a child ingesting normal amounts of gluten and having normal jejunal mucosal morphology on biopsy and a normal density of γδ+ T cells. [ABSTRACT FROM AUTHOR]

Anti-tissue transglutaminase has been recently described as the predominant autoantigen in coeliac disease. We purified serum anti-tissue transglutaminase antibodies from three patients with coeliac disease by column chromatography and eluted tissue section-bound R1-anti-reticulin antibodies from sections of rat tissue for two of these. Lastly, we generated seven mouse MoAbs to guinea pig tissue transglutaminase. Each preparation was examined for anti-tissue transglutaminase, anti-endomysium, anti-R1 reticulin and anti-gliadin antibodies. Column-purified patient antibodies and 2/7 mouse MoAbs gave characteristic anti-endomysium/anti-R1 reticulin reactivity on rat, monkey and human tissue. All positive sera gave indistinguishable patterns of immunofluorescence on rat liver, kidney and stomach, monkey oesophagus, and human umbilical cord. Anti-R1-reticulin eluted from sections showed anti-tissue transglutaminase reactivity in 2/2 cases, but 0/2 showed anti-gliadin reactivity. In both, tissue section-eluted anti-R1 reticulin gave endomysial staining on monkey oesophagus. None of the mouse monoclonals, or any of the purified patient's anti-tissue transglutaminase or anti-R1-reticulin antibody showed any reactivity with gliadin. These data confirm tissue transglutaminase as the predominant autoantigen in coeliac disease and suggest that both anti-endomysium and anti-R1 reticulin reactivities seen in coeliac disease arise due to an immune response to tissue transglutaminase. Rigorous immunoabsorption was sufficient to abrogate reactivity in the tissue transglutaminase ELISA, but failed to completely absorb anti-endomysium and anti-reticulin activity. The possibility remains that some of the anti-endomysium and anti-reticulin activity was directed against antigens other than tissue transglutaminase. [ABSTRACT FROM AUTHOR]

It has previously been reported that gliadins bind to reticulin in tissue sections. Three lines of evidence are reported in this study which indicate that the gliadins bind to reticulins because they are lectins which bind to sugars expressed on glycoproteins in reticulin and other sites. First, immunofluorescence studies on tissue sections showed that although gliadin binding is largely confined to areas rich in reticulin, it is, nonetheless, also seen in one or two other sites devoid of reticulin. Second, by using fluorescein-labelled lectins of known specificity, it has been shown that the areas to which gliadins bind in tissue sections (including those sites devoid of reticulin) are rich in particular sugars. Third, it has been shown that one of these sugars, α- d-mannose, partially inhibited gliadin binding to tissue sections. [ABSTRACT FROM AUTHOR]

The distribution of amyloid P component in the adult human thyroid was studied by direct immunofluorescence on frozen sections of surgically removed tissue. Amyloid P component shows a striking fibrillary and broken linear distribution in the interfollicular areas. This pattern corresponds to that of reticulin fibres. Amyloid P is also localised to the small amount of elastic tissue in blood vessels but is not demonstrable within cells or in acinar basement membranes. [ABSTRACT FROM AUTHOR]

Adrenal cortical carcinoma (ACC) is a rare cancer with poor prognosis that needs to be distinguished from adrenocortical adenomas (ACAs). Although, the recently developed transcriptome analysis seems to be a reliable tool for the differential diagnosis of adrenocortical neoplasms, it is not widely available in clinical practice. We aim to evaluate histological and immunohistochemical markers for the distinction of ACCs from ACAs along with assessing their prognostic role. Clinical data were retrospectively analyzed from 37 patients; 24 archived, formalin-fixed, and paraffin-embedded ACC samples underwent histochemical analysis of reticulin and immunohistochemical analysis of p27, p53, Ki-67 markers and were compared with 13 ACA samples. Weiss and Helsinki scores were also considered. Kaplan−Meier and univariate Cox regression methods were implemented to identify prognostic effects. Altered reticulin pattern, Ki-67% labelling index and overexpression of p53 protein were found to be useful histopathological markers for distinguishing ACAs from ACCs. Among the studied markers, only pathological p53 nuclear protein expression was found to reach statistically significant association with poor survival and development of metastases, although in a small series of patients. In conclusion, altered reticulin pattern and p53/Ki-67 expression are useful markers for distinguishing ACCs from ACAs. Immunohistopathology alone cannot discriminate ACCs with different prognosis and it should be combined with morphological criteria and transcriptome analysis. [ABSTRACT FROM AUTHOR]