Liver failure with green neutrophilic inclusions after liver transplantation: a case report / 中华检验医学杂志

We report a case of a 44-year-old female patient with acute liver failure and hepatic encephalopathy. The patient received artificial liver treatment and underwent allogeneic orthotopic liver transplantation at 14 days after admission. Laboratory examination reported a small number of green cytoplasmic inclusions in neutrophils on the peripheral blood smear at 68 days after admission. The patient eventually died of liver failure at 71 days after admission. Green inclusions are bright green or blue-green inclusions presented in the cytoplasm of neutrophils in Wright-Giemsa stained peripheral blood smears, and is associated with liver failure and high short-term mortality.

Morphological characteristics of bone marrow and peripheral blood in 1 151 cases diagnosed with de novo acute leukemia / 中华检验医学杂志

Objective:To observe and analyze the morphological characteristic of bone marrow and peripheral blood in patients diagnosed with de novo acute leukemia.Methods:From October 1, 2015 to December 31, 2021, 1151 patients aged 47 (26, 62) years, consisting of 602 males and 549 females with newly diagnosed acute leukemia in the Department of Hematology, Affiliated Hospital of Xuzhou Medical University, were collected to preform the morphological analysis in bone marrow and peripheral blood smears. Based on the comprehensive diagnosis results of morphology, immunology, cytogenetics, and molecular biology, comparison between acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), AML with RUNX1-RUNXITI gene, AML with CBFβ/MYH11 gene, acute promyelocytic leukemia (APL) with PML/RARA gene, AML with NPM1 gene, the rest of the AML, Ph+ALL and Ph-ALL were performed by Chi-square test along with analysis of the differences in the ratio of wood bundle cells, pseudo-Chediak-Higashi (PCH) inclusions, cytoplasmic small particles, nuclear notches, leukemia cells with cup-like changes (cup cells); as well as the differences in the micromeganuclei, early immature granulocytes, plasma cells, high eosinophils and other accompanying cells and the distribution of "grape-like" aggregation. Finally, the morphological characteristics of acute leukemia cells, the appearance and arrangement of accompanying cells were summarized.Results:Between AML and ALL, there were statistically significant differences in cytoplasmic Auer bodies[(45.5%, 0%), χ 2=211.400, P<0.01], PCH inclusion bodies[(28.9%, 0%), χ 2=114.100, P<0.01], cytoplasmic fine particles[(20.7%, 2.9%), χ 2=53.798, P<0.01], nuclear notches[(0.7%, 6.1%), χ 2=30.906, P<0.01], and goblet cells[(4.9%, 0.3%), χ 2=13.495, P<0.01], micromegakaryus [(22.4%, 0.3%), χ 2=80.398, P<0.01], plasma cells[(87.6%, 10.6%), χ 2=604.241, P<0.01], hyperacidophils[(15.3%, 1.0%), χ 2=46.116, P<0.01] showed significant differences in the "grape-like" aggregation distribution. In AML with RUNX1-RUNXITI gene, the changes of vacuoles and PCH inclusion bodies are more obvious; in AML with CBFβ/MYH11 gene, the increase of hypereosinophils is more obvious; in APL with PML/RARA gene, the increase of woodbundle is more obvious. The morphology of nuclei chromatin, nucleolus, and vacuoles were also different among the groups. Comparison between Ph+ALL and Ph-ALL showed that Ph+ALL was more prone to develop early immature granulocytes and plasma cells (all P<0.05). Conclusion:There are significant differences between AML and ALL in the characteristics of leukemia cells, the regularity of accompanying cells, and the aggregation and distribution patterns. The subtypes of AML with specific genetic abnormalities have their own characteristics in the appearance of vacuoles, PCH inclusions, hypereosinophils, woodbundle cells, and goblet cells. Ph+ALL is more prone to present early immature granulocytes and plasma cells.

Electron microscopy in the diagnosis of skeletal muscle disorders: Its utility and limitations

Electron microscopy (EM) has a substantial role in the diagnosis of skeletal muscle disorders. The ultrastructural changes can be observed in muscle fibers and other components of the muscle tissue. EM serves as a confirmatory tool where the diagnosis is already established by enzyme histochemistry staining. Although it is indispensable in the diagnosis of rare forms of congenital myopathies not appreciated by light microscope, such as cylindrical spiral myopathy, zebra body myopathy, fingerprint body myopathy, and intranuclear rod myopathy, in cases not subjected to histochemical staining, it is required for definitive diagnosis in certain groups of muscle disorders, which includes congenital myopathies, metabolic myopathies in particular mitochondrial myopathies and glycogenosis, and in vacuolar myopathies. It does not have diagnostic implications in muscular dystrophies and neurogenic disorders. In the recent past, despite the availability of advanced diagnostic techniques, electron microscopy continues to play a vital role in the diagnosis of skeletal muscle disorders. This review gives an account of ultrastructural features of skeletal muscle disorders, the role of EM in the diagnosis, and its limitations.

Non-granulomatous inflammatory lesions of CNS: Approach to diagnosis

Infections constitute an important and common category of diseases, particularly in less developed countries. Infections present with a broad spectrum of clinical and radiologic features dictated by the cell and tissue tropism and host response elicited, posing a considerable diagnostic challenge. Early diagnosis and treatment are crucial in preventing mortality and morbidity. Recourse is often made to biopsy for ascertaining the diagnosis, and hence the pathologist plays a vital role in patient management. Therefore, knowledge of the histopathologic changes is necessary to recognize the histological changes and guide the diagnostic workup and management. Each microbial agent elicits a distinctive pattern of inflammatory tissue response, which can serve as a clue to the etiological agent. Based on the causative organism, microbial, and host factors, the inflammatory response may be acute or chronic, necrotic or non-necrotic. The inflammation can be of varied patterns – lymphohistiocytic, granulomatous, inflammatory demyelinating, fibrosing, or showing minimal inflammation. The pattern of necrosis also differs based on the causative organism. Typically, pyogenic bacteria are associated with suppurative inflammation, tuberculosis with caseous granulomatous, and fungi with suppurative granulomatous inflammation. Viral infections are associated with lymphohistiocytic non-necrotizing inflammation and, based on cell tropism, can cause demyelination (e.g., JCV) and/or viral inclusions. Parasitic infections (protozoal or metazoal) display a broad spectrum of inflammatory changes that overlap with other types of infections. This review briefly describes pathological patterns and associated pathogens and provides an algorithmic approach based on pattern recognition that may be useful for the practicing pathologist.

Auer rod?like inclusions in multiple myeloma: Report of two diagnostically challenging cases

Non-immunoglobulin intracytoplasmic inclusions in plasma cells of multiple myeloma are very rare presentation. These are morphologically similar to Auer rods but chemically different from them. We studied two cases of multiple myeloma in a 60-year-old woman and 45-year-old man. In both cases, plasma cells of bone marrow aspirate revealed multiple Auer rod-like inclusions (ARLI). Sudan black B (SBB) and myeloperoxidase (MPO) cytochemistry were negative. Serum protein electrophoresis in both of them showed M spike, one with raised IgA-kappa levels, while the other with raised IgG-kappa levels. Very few case reports have been published in the literature and its prognostic implications are still unknown. Due to its rarity, it is important to distinguish such cases from acute myeloid leukemia and its exact incidence with its therapeutic and prognostic implications

A Chinese pedigree of familial encephalopathy with neuroserpin inclusions bodies / 中华神经科杂志

Objective:To report the clinical and genetic features of a pedigree with familial encephalopathy with neuroserpin inclusions bodies (FENIB) and to enhance the understanding of the disease.Methods:The proband was admitted to Department of Neurology, Henan Provincial People′s Hospital in June 2020 due to cognitive impairment and epilepsy. Detailed medical history inquiry, physical examinations, and neuroimaging examination of the family were conducted. The proband completed the examination of brain magnetic resonance imaging (MRI), electroencephalogram (EEG), cerebrospinal fluid examinations. Whole exome sequencing and Sanger sequencing were used to screen the genetic variations in the proband. Sanger sequencing was performed in some family members to verify the mutation. Through literature review, the characteristics of the disease were summarized.Results:The proband was a 23-year-old young female with progressive cognitive impairment, epilepsy as the main manifestations. Brain MRI indicated moderate atrophy of bilateral cerebral cortex. Genetic sequencing revealed a heterozygous missense mutation (c.1013A>G; p.H338R) of SERPINI1 gene encoding the neuroserine protease inhibitor protein. The proband′s mother and brother had similar clinical symptoms in adolescence. Both of them passed away several years later. This mutation was a proven pathogenic mutation for FENIB. The clinical phenotype was consistent within the family. Genotype and clinical phenotype were co-segregated.Conclusion:FENIB due to SERPINI1 gene mutations should be considered in young cases of cognitive decline, epilepsy and myoclonus.

Role of the C9ORF72 Gene in the Pathogenesis of Amyotrophic Lateral Sclerosis and Frontotemporal Dementia / 神经科学通报·英文版

Since the discovery of the C9ORF72 gene in 2011, great advances have been achieved in its genetics and in identifying its role in disease models and pathological mechanisms; it is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). ALS patients with C9ORF72 expansion show heterogeneous symptoms. Those who are C9ORF72 expansion carriers have shorter survival after disease onset than non-C9ORF72 expansion patients. Pathological and clinical features of C9ORF72 patients have been well mimicked via several models, including induced pluripotent stem cell-derived neurons and transgenic mice that were embedded with bacterial artificial chromosome construct and that overexpressing dipeptide repeat proteins. The mechanisms implicated in C9ORF72 pathology include DNA damage, changes of RNA metabolism, alteration of phase separation, and impairment of nucleocytoplasmic transport, which may underlie C9ORF72 expansion-related ALS/FTD and provide insight into non-C9ORF72 expansion-related ALS, FTD, and other neurodegenerative diseases.

Role of the C9ORF72 Gene in the Pathogenesis of Amyotrophic Lateral Sclerosis and Frontotemporal Dementia / 神经科学通报·英文版

Since the discovery of the C9ORF72 gene in 2011, great advances have been achieved in its genetics and in identifying its role in disease models and pathological mechanisms; it is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). ALS patients with C9ORF72 expansion show heterogeneous symptoms. Those who are C9ORF72 expansion carriers have shorter survival after disease onset than non-C9ORF72 expansion patients. Pathological and clinical features of C9ORF72 patients have been well mimicked via several models, including induced pluripotent stem cell-derived neurons and transgenic mice that were embedded with bacterial artificial chromosome construct and that overexpressing dipeptide repeat proteins. The mechanisms implicated in C9ORF72 pathology include DNA damage, changes of RNA metabolism, alteration of phase separation, and impairment of nucleocytoplasmic transport, which may underlie C9ORF72 expansion-related ALS/FTD and provide insight into non-C9ORF72 expansion-related ALS, FTD, and other neurodegenerative diseases.

The Importance of Eosinophilic Cytoplasmic Inclusion Bodies in Melanocytes as a Clue to Distinguish between Benign and Malignant Melanocytic Lesions.

Aim: Since early diagnosis and treatment of melanoma can significantly improve patients’ prognosis, discovering new criteria to help differentiate between benign and malignant melanocytic lesions is of significance. In this study we aim to clarify the relationship between the presence of intracytoplasmic eosinophilic inclusion bodies inside melanocytes and the nature of the melanocytic lesion. Methods: Medical records and pathology slides pertaining to 187 patients with melanocytic lesions who had undergone biopsy in Razi Hospital between March 2014 and March 2015 were gathered. Slides were re-examined by a dermatopathologist using a light microscope. Clinical and pathological data were analyzed using SPSS. Results: A total of 196 specimens from 187 patients were studied. The median age of our patients was 42.26 years and 61.5% of them were female while 38.5% were male. The specific eosinophilic intracytoplasmic inclusion bodies were observed in 14 specimens; 8 of which were intradermal nevi and the remaining 6 were from compound nevi. These bodies tended to be present in lesions with congenital features. We found no correlation between age, sex or location of the lesion with the presence of aforementioned bodies. Conclusion: Eosinophilic inclusion bodies present in the cytoplasm of melanocytes are associated with benign melanocytic lesions and are mostly observed in cells with abundant vacuolated cytoplasm and in lesions with congenital features. Therefore these bodies can be helpful in diagnosing benign and longstanding lesions and differentiating them from malignancies.

Secretory meningioma: A diagnostic pitfall.

Context: Secretory meningioma is a rare subtype of meningiomas, displaying epithelial and secretory differentiation of meningothelial cells. It has unique radiological, morphological, and immunohistochemical features, but runs a benign course. Radiological picture because of the variable degrees of peritumoral edema can be confused with aggressive neoplasms. Morphologically, it is diffi cult to distinguish secretory meningioma from other tumors having a clear cell appearance and aggressive clinical behavior. Materials and Methods: Retrospective analysis over a period of 16 years (1997-2012) brought out fi ve cases diagnosed as secretory meningioma. The slides were restained and subject to special stains and immunohistochemistry and the clinical details were retrieved. Results: On histopathology, the tumors showed a characteristic vacuolated appearance due to the presence of variably sized intracytoplasmic lumina. Another unique feature was the presence of hyaline inclusions within these intracytoplasmic lumina and in the intercellular spaces. These inclusions were periodic acid-Schiff positive diastase-resistant, yellowish-orange on Elastic Van Giesson stain and strongly carcinoembryonic antigen positive. Conclusion: Owing to its rarity and unique morphology secretory meningioma poses a diagnostic challenge to the pathologists. As this tumor follows a benign course, it is crucial to correctly diagnose this entity to avoid unnecessary over treatment.

The Role of Electron Microscopy in the Assessment of Dermatomyositis: A Retrospective Pilot Study on Skeletal Muscle Biopsies.

Aims: To assess the contribution of electron microscopy in the process of muscle biopsies evaluation for dermatomyositis. Study Design: Retrospective review of muscle biopsy cases. Place and Duration of Study: Pathology Department of King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia from January 2008 to January 2012. Methodology: Samples from cases suspected to have dermatomyositis were reviewed for light and ultrastructural morphological examination. Tubuloreticular inclusions (TRI) were considered present if these undulating tubules were detected in the endothelial cells of the capillaries. Results: Out of ten cases that were suspected for dermatomyositis, three cases showed classical light microscopic features of dermatomyositis, two of which showed TRI. Among four cases with non-specific light microscopic features that can be seen in dermatomyositis, TRI were detected in two of these four cases. Among three cases with non-contributory light microscopy, TRI were found in all of these three cases. Conclusion: Electron microscopy -if feasible- may be useful in the screening of muscle biopsies, when clinically or morphologically suspected inflammatory myopathies are considered. Further studies to assess the significance of TRI with a larger number of cases, clinical data correlation and immunostains are needed.

The Cytologic Features of Desmoplastic Small Round Cell Tumor with Intranuclear Inclusions : A Case Report

Desmoplastic small round cell tumor (DSRCT) is a rare neoplasm of young adults and it is characterized by polyphenotypic differentiation. We experienced a case of abdominal DSRCT that occurred in a 19-year-old female who presented with painful swelling of her right forearm. The tumor was cytokeratin-negative and it exhibited some tumor cells with intranuclear inclusions. Molecular demonstration of EWS-WT1 fusion transcripts is particularly useful to confirm the diagnosis of DSRCT without epithelial differentiation. We report here on a case of cytokeratin-negative DSRCT that showed an unusual feature of intranuclear inclusions.

Protein Components of Lewy Bodies (LBs) Identified from Synthetic Proteasome Inhibitor (PSI)-induced Inclusions in PC12 Cells by MS Analysis / 中国生物化学与分子生物学报

Proteomic analysis is an effective way to identify protein constituent in Lewy bedy-like inclusions (or aggresome) in vitro. Exposure to synthetic proteasome inhibitor (PSI, 10 μmol/L) for 48 hours was used to induce the formation of cytoplasmic proteineous inclusions (termed as PSi-induced inclusions) in PC12 cells.The proteomic approaches of biochemical fractionation, two-dimensional electrophoresis (2-D) and identification via peptide mass fingerprints (PMF) were deployed, and 20 protein components of LBs were identified,i ncluding 2 proteins involved in the production of synaptic neurotransmitter, 6 subunits of the 26 S proteasome,2 cytoskeleton proteins, 2 subunits of mitochondrial complexes, 1 anti-oxidant protein, and 7 chaperone proteins and (or) chaperone-like proteins. The results suggested that these LB protein components might had been recruited in PSI-induced inclusions formed in PC12 cells under the condition of proteasome inhibition.

Clinical Course of IgA Nephropathy in Children

A statistical analysis of the diagnostic value for 244 aspiration biopsy cytology(ABC) among a total 1,043 cases from various sites was performed. ABC, using diagnostic terminology similar to that of a surgical pathology reports, was compared to the final tissue diagnosis. For the entire series, a sensitivity of 91.8%, a specificity of 99.3%, a positive predictive value of 98.9%, a negative predictive value of 94.8%, and an efficacy of the test of 96.3% were shown. There were 8 false negative and 1 false positive diagnosis. The diagnostic accuracy was 89.8%. Those results indicate that the ABC is a considerably highly accurate procedure that should be routinely employed.

Malignant Rhabdoid Tumor of the Kidney: A report of two cases: An immunohistochemical and ultrastructural study

Malignant rhabdoid tumor of the kidney(MRTK), an uncommon renal tumor found in children, is one of the most lethal neoplasms of early life. It was first recognized during a review of the first National Wilms' Tumor Study(NWTS) as an extremely aggressive neoplasm whose appearance often mimicks those of skeletal muscle tumors, but without histological, immunohistochemical, and ultrastructural markers of rhabdomyogenesis. Herein we present two cases of malignant rhabdoid tumor of the kidney, one occurring in a 6-month-old male baby, and the other in a 123-month-old girl. They presented a huge tender mass on the left upper quadrant of the abdomen. Microscopically, each case was very cellular and composed of sheets of round or polygonal cells with ample cytoplasm often containing eosinophilic filamentous inclusions and round vesicular nuclei with prominent nucleoli. Case 1 showed lymphomatoid pattern, but case 2 showed foci of several variant patterns associated with classic appearances. The tumor cells showed a strong reactivity for vimentin in both cases. Unusually, case 2 showed focal reactivity for epithelial membrane antigen(EMA), muscle specific actin, and smooth muscle actin. Ultrastructural study confirmed the presence of whorled bundles of intermediate filaments in paranuclear position, and a prominent nucleolus.

The clinical significance of cytoplasmic inclusions(CPI) in synovial fluid examination

The clinical significance of cytoplasmic inclusions(CPI) in synovial fluid(SF) examination was evaluated. We examined SF specimens collected from major rheumatology clinics in the Philadelphia area during the period of January to December 1995. Among 759 patients in the initial study group, 419 cases with established diagnoses and full synovial analyses were included. Their diagnoses and SF analysis results including leukocyte counts, differential counts and wet preparations were collected and analysed. Ninety seven of the 419 SF specimens were found to have CPI. CPI were found in SF from almost all rheumatic diseases. They were most likely to be found in inflammatory arthropathy including rheumatoid arthritis(RA, 46%), juvenile rheumatoid arthritis(JRA, 78%) and psoriatic arthritis(55%). On the contrary, CPI were least common in crystal-induced arthropathy among the inflammatory arthropathy. CPI were found 8 out of 98 gout cases(8%) and 2 among 53 calcium pyrophosphate dihydrate(CPPD) deposition disease(4%). In noninflammatory arthropathy, CPI were found in only 6 cases(6%) out of the 103 osteoarthritis(OA). In RA cases with non-inflammatory SF, 4 of the 20 SF(20%) had CPI while only 6% of OA SF had CPI. OA SF with CPI were all noninflammatory SF. In summary, CPI were a common finding on SF examination. CPI were more likely to be found in inflammatory arthropathy than noninflammatory. Among inflammatory arthropathy, CPI can favor non-crystal arthropathy than crystal arthropathy. Awareness of the presence of CPI is suggested as an addendum to routine SF analysis. Renewed investigation of the several types of CPI may add further to the understanding of joint disease.

Comparison of inclusions in female and male Trichosanthes kirilowii individuals / 中草药

Objective To analyze the different composition and contents of inclusion in female and male Trichosanthes kirilowii individuals and to provide some references for the early sex identification.Methods Physiological and biochemical indices in T.kirilowii leaves were determined and significant analysis of the difference was performed.The difference of chemical composition was analyzed using HPLC.Results The contents of photosynthetic pigments and soluble proteins,the activities of superoxide dismutase(SOD) and peroxidase(POD),and the DNA concentration were higher in male individuals than those in female ones.The difference in photosynthetic pigments content and POD activity reached a significant level.The female individuals possessed higher contents of malondiadehycle(MDA),soluble saccharide,and UV-absorbing compounds than those in male ones,and the difference in UV-absorbing compounds reached a significant level.HPLC Assay revealed obvious differences in the peaking frequency,time,and the peak height.Conclusion There are differences in the composition and contents of inclusions in male and female T.kirilowii individuals,and the UV-absorbing compounds and the characteristic HPLC peak could potentially be as indices of sex identification.

Human Rabies Encephalomyelitis——A Report of 8 Autopsy Cases / 第三军医大学学报

Eight cases of human rabies encephalomyelitis confirmed by autopsy were reported. They all had a history of rabid dog bite and typical clinical manifestations of rabies. The mean clinical course ran about 4 days. The most frequent pathological findings were the appearence of intracytoplasmic Negri bodies in neuron and paren-chymal inflammation of the brain and spinal cord. The inflammatory response was more prominent in the brainstem, hippocampus and spinal cord, consisting of peri-vascular cuffs of lymphocytes and monocytes, foci of softening microglial response and neuronophagia. Negri bodies were found in all of the sections taken from the brain, especially frequently found in the purkinjs cells of the cerebsll um and the pyramidal cells of the hippocampi in all the eight cases.The pathodiagnostic principles of this disease, and its differentiation from type B encephalitis and polimyelitis were briefly discussed. The relation between the site of the dog bite and the distribution of the lesions and the duration of the incubation period were also discussed.

An Electron Microscopic Observation on the Weibel-Paladelike body in the Growth Hormone Cell and Follicular - stellate Cell of Rabbit / 第三军医大学学报

The Weibel-Palade-like body were found in the cytoplasm of the growth hormone and follicullar - stellate cells of rabbit adenopypophsis. The body is surrounded by a single unit membrane. In this body, there are numerous of microtubules which can be divided into two groups depending upon their diameters.Yet, it is uncertain what the virtual function is and where the bodies come from. However, according to the experimental observations, it is suggested that the body serve as a mechanical power device which has relations with the regional distribution of the organelles. The intranuclear microtubules and intranuclear tubules were also found in the growth hormone cells. The diameters of these intranuclear microtubules range from 25 - 30 nm, and the intranuclear tubule about 78 nm. The fomer seems to be connected with the heterochromatin granules, and may be. a transitional pattern from heterochromatin to euchromatin, but their importance remain to be clarified.

IgD MYELOMA WITH INTRACYTOPLASMIC CRYSTALLINE INCLUSIONS / 第二军医大学学报

A case of IgD(kappa light chains type)multiple myeloma with intracytoplasmic crystalline inclusions is reported.Light microscopic and electron microscopic exeminat-ions are carried out with a view to compare the morphologic and ultrastructural features of myeloma cells.Moreover, the relationship between the biochemistry of intra-cytoplasmic crystalline inclusions and that of Russell's bodies are discussed.