Research advances on polyglycine diseases / 中华神经科杂志

Nucleotide repeat expansion is one of the common causes for neurodegenerative disorders. Polyglycine diseases are a newly defined neuro- and muscle- degenerative disease spectrum characterized by CGG trinucleotide repeat expansions, generation and aggregation of aberrant polyglycine protein, and formation of intranuclear inclusions. To date, the aggregation of pathogenic polyglycine protein has been proved in fragile X-associated tremor/ataxia syndrome and neuronal intranuclear inclusion disease. In recent years, the case load of these diseases grows rapidly with the increasing awareness and developing genetic testing technologies. This article aims to systematically review the recent progress in polyglycine diseases, and probe into their pathogenic mechanisms as well as clinical concerns.

Research progress in neuronal intranuclear inclusion disease / 中华神经科杂志

Neuronal intranuclear inclusion disease (NIID) is a slowly progressive neurodegenerative disease characterized by localized neuronal loss,and the presence of eosinophilic intranuclear inclusions in neurons and glial cells.Biopsy samples of skin,rectal and sural nerve showed hyaline intranuclear inclusions.Reported NIID cases showed familial type according to family history,and three clinical subgroups (infantile,juvenile and adult form) according to onset and disease duration.NIID has been considered as a heterogeneous disease because of the highly variable clinical manifestations including cognitive dysfunction,parkinsonism,cerebellar ataxia,peripheral neuropathy and autonomic dysfunction.Additionally,some NIID cases presented episodes of conscious disturbance,cognitive decline,movement disorder or even fever.Head magnetic resonance imaging of some patients revealed symmetrical leukoencephalopathy in T2 image and fluid attenuated inversion recovery image and high intensity signal in corticomedullary junction in diffusion weighted image.But it is not the only abnormal finding of imaging,and other diseases may also present the similar changing.Other diseases including fragile X-associated tremor-ataxia syndrome,Huntington's disease and spinocerebellar ataxia should be considered in differential diagnosis.

Ultrastructural and clinical findings of mitochondrial encephalomyopathy:report of 27 cases / 中华病理学杂志

Objective@#To investigate the ultrastructural features of muscle in patients with mitochondrial encephalomyopathy for its diagnosis and differential diagnosis.@*Methods@#The clinical data of 27 mitochondrial encephalomyopathy patients who underwent left or right biceps brachii muscle biopsy at Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University from July 2006 to August 2017 were analyzed retrospectively. The muscle biopsy specimens were examined underlight microscope and transmission electron microscope.@*Results@#There were 27 patients (17 males, 10 females) with an age range of 12 to 62 years (mean 29 years). The age of onset ranged from 3 to 38 years. The course of disease ranged from 1 month to 24 years. Twenty-two cases presented with lactic acidosis and stroke-like episodes (MELAS) syndrome, four with myoclonic epilepsy with ragged red fibers (MERRF) syndrome, and one with chronic progressive paralysis of extraocular muscle (CPEO) syndrome. Skeletal muscle biopsy showed abundant ragged red fibers and strongly SDH-reactive vessel. Genetic studies showed 17 of 22 cases of MELAS syndrome had A3243G mutation, and the other 5 cases had no abnormality. A8344G mutation was found in 3 of 4 cases of MERRF syndrome. No single or multiple mtDNA mutations were found in the single case of CPEO. Transmission electron microscopy of all 27 cases showed diffuse proliferation of mitochondria between the myofibrils and beneath the sarcolemma, with increased spacing between muscle cells. Seven cases showed numerous glycogen and four showed subsarcolemmal lipid droplets, 13 cases showed unusual mitochondrial morphology, including mitochondrial electron-dense substances and paracrystal line inclusions ("parking lot" change)in eight cases.@*Conclusions@#Transmission electron microscopy shows significant differences in ultrastructural pathological changes among different patients with mitochondrial encephalomyopathy. Some patients with mild clinical symptoms have increased mitochondrial number, increased metabolism of glycogen and lipid droplets, while others with severe clinical symptoms have abnormal mitochondrial morphology. Typical crystalloid inclusions are found in mitochondria, which are of great value in the diagnosis of this disease.

Fatal Disseminated Herpes Simplex in a very premature neonate

Herpes Simplex Virus infections (HSV) are ubiquitous. The neonatal HSV infection (NHSV) is rare. The incidence is estimated globally at only 10.3 per 100,000 births, but it can cause devastating disease in premature infants. Both HSV-1 and HSV-2 can be the etiologic agents in this type of vertically transmittted NHSV infection. Here we describe the pathological findings from a complete autopsy of a very low birth weight infant who succumbed to the infection despite early institution of antiviral treatment. We urge more awareness of this disease with continued surveillance; every effort should be taken to make an early diagnosis and thus prevent this devastating disease.

Adult-onset neuronal intranuclear inclusion disease: a case report and review of literature / 中华神经科杂志

The clinical, pathological features and diagnostic methods of one case of adult-onset neuronal intranuclear inclusion disease (NIID) were analyzed. The patient was 61-year-old female presented with progressive cognitive impairment, episodic unconsciousness, stroke-like attack and paroxysmal digestive tract symptoms. Diffusion-weighted images showed high signals at the cerebral cortico-medullary junction with lace-type distribution, which persisted. Skin biopsy revealed intranuclear inclusion bodies in adipocytes, fibroblasts, and sweat gland cells. This case suggests that adult neuronal nuclear inclusion disease is a chronically progressive neurodegenerative disease with a highly clinical heterogeneity. The subcortical lace sign and eosinophilic intranuclear inclusion bodies by skin biopsy contribute to the diagnosis.

Terapias oncoespecíficas en pacientes con virus del herpes simple bucal / Oncospecific therapies in patients with herpes simplex virus

Se efectuó un estudio descriptivo y transversal de 25 pacientes con cáncer infectados por el virus del herpes simple bucal, quienes tenían el sistema inmunológico deteriorado debido al tratamiento oncoespecífico, atendidos en la consulta estomatológica del Policlínico de Especialidades del Hospital Provincial Docente Clinicoquirúrgico Saturnino Lora Torres de Santiago de Cuba, desde enero de 2014 hasta igual mes de 2016, a fin de evaluar los resultados del diagnóstico clínico y citopatológico de esta afección. En la casuística prevalecieron el sexo masculino, el dolor como sintomatología clínica, el bermellón del labio inferior como el sitio de mayor incidencia y la quimioterapia como la modalidad terapéutica de mayor reactivación de este agente viral. La citología exfoliativa confirmó la presencia de células epiteliales gigantes multinucleadas con cuerpos de inclusiones intranucleares y necrosis de células infectadas, respectivamente, siendo estos los hallazgos microscópicos más significativos

A descriptive and cross-sectional study of 25 patients with cancer infected by the oral herpes simplex virus was carried out. They had the immunologic system damaged due to oncospecific treatment, assisted in the stomatological service of the Specialties Polyclinic of Saturnino Lora Torres Teaching Clinical Surgical Provincial Hospital in Santiago de Cuba, from January, 2014 to the same month in 2016, in order to evaluate the results of the clinical and cytopathologic diagnosis of this disorder. In the case material the male sex and pain as clinical symptomatology, the vermilion of the lower lip as the place of more incidence and chemotherapy as the therapeutic modality of this viral agent higher reactivation prevailed. The exfoliative cytology confirmed the presence of multinucleous giant epithelial cells with bodies of intranuclear inclusions and infected cells necrosis, respectively, being these the most significant microscopic findings

Cytologic Features of Giant Cell Ependymoma: A Case Report and Review of the Literature

Here, we present a case of anaplastic giant cell ependymoma (GCE) occurring in a 15-year-old woman. Squash smear slides for intraoperative frozen section diagnosis revealed oval to round cell clusters with a papillary structure in a fibrillary background. This was occasionally accompanied by the presence of bizarre pleomorphic giant cells with hyperchromatic nuclei and prominent intranuclear inclusions. These intranuclear inclusions were a key clue to diagnosis of ependymoma. Histologic analysis revealed features of a high-grade tumor with perivascular pseudorosettes and bizarre pleomorphic giant cells, which established the diagnosis of GCE. We performed a review of literatures about the cytologic features of GCE, including our case, thus proposing that intraoperative frozen diagnosis of GCE would be established by squash smear preparations featuring the mitosis and necrosis, as well as the high cellularity, and the presence of giant cells showing hyperchromatic nuclei with eosinophilic cytoplasm and intranuclear inclusions/pseudoinclusions.

Parvovirus B19 presenting with persistent pancytopenia in a patient of T-ALL post induction chemotherapy diagnosed on bone marrow examination.

Manifestations of parvovirus B19 vary even in the normal host from asymptomatic or subclinical infection to a spectrum of illness with symptoms during viremic and immune complex mediated stage of disease. We report the morphological findings of parvovirus B19 infection (confirmed on serology) in a patient of T-acute lymphoblastic lymphoma (T-ALL) who underwent induction phase of chemotherapy (MCP 842 protocol). Persistent pancytopenia in the bone marrow aspirate with mild increase in blasts was thought to be due to failure to achieve marrow remission. However, giant pronormoblasts with prominent intranuclear inclusions confirmed on trephine biopsy led to the suspicion of parvovirus B19 infection which was later confirmed on serology. This case is presented to report the rarely seen classical morphological feature of parvovirus infection on bone marrow examination which was incidentally the first investigation to diagnose the viremic phase of the infection, indicating that a high index of suspicion needs to be kept in mind while examining bone marrows of susceptible patients.

Juxtacortical Glomus Tumor of the Tibia with an Uncertain Malignant Potential

Glomus tumors are mesenchymal neoplasms that are composed of modified smooth muscle cells of the normal glomus body. Most glomus tumors are benign and they occur in the distal extremities, and particularly the subungual lesions that occur in the hand, the wrist and the foot. We report here on a case of a solid type glomus tumor that had an uncertain malignant potential with a juxtacortical location at the distal tibia, and there were no neoplastic erosion of the cortical surface and no periosteal reaction. The tumor cells showed mild nuclear atypia and moderate mitotic activity (3-5/10HPF). Prominent intranuclear cytoplasmic pseudoinclusions were also observed. This case is interesting due to the very unusual tumor location of the juxtacortical area of the long bone, the atypical histologic features and the unique cytological finding of cytoplasmic intranuclear inclusions throughout the tumor cells.

Multiple Glomus Tumors of the Ankle with Prominent Intranuclear Pseudoinclusions

Glomus tumors are neoplasms that are composed of modified smooth muscle cells of the glomus body. Here, we report a case of multiple glomus tumors of the ankle that showed various histologic types, including the solid type (glomus tumor proper) and angiomatous type (glomangioma). The tumor cells observed in this case also showed prominent intranuclear inclusions, which has not yet been reported in glomus tumors. Ultrastructural examination demonstrated that the nuclear inclusions were not true inclusion bodies but were intranuclear cytoplasmic pseudoinclusions formed by cytoplasmic invaginations that formed as a result of the deep and complex nuclear contours.