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Alveolar rhabdomyosarcoma (ARMS) with FOXO1 gene rearrangements is an aggressive pediatric rhabdomyosarcoma subtype that is prognostically distinct from embryonal rhabdomyosarcoma and fusion-negative ARMS. Herein, we report two cases of ARMS with PAX3::MAML3 fusions. The tumors arose in an infant and an adolescent as stage IV metastatic disease (by Children's Oncology Group staging system). Histologically, both cases were small round blue cell tumors arranged in vague nests and solid sheets that were diffusely positive for desmin and myogenin. By methylation profiling and unsupervised clustering analysis, the tumors clustered with ARMS with classic FOXO1 rearrangements and ARMS with variant PAX3::NCOA1/INO80D fusions, but not with biphenotypic sinonasal sarcoma (BSNS) with PAX3::MAML3/NCOA2/FOXO1/YAP1 fusions, nor with other small round blue cell tumors, including embryonal rhabdomyosarcoma. The differentially methylated genes between ARMS and BSNS were highly enriched in genes involved in myogenesis, and 21% of these genes overlap with target genes of the PAX3::FOXO1 fusion transcription factor. On follow-up after initiation of vincristine/actinomycin/cyclophosphamide chemotherapy, the tumors showed partial and complete clinical response, consistent with typical upfront chemotherapy responsiveness of ARMS with the classic FOXO1 rearrangement. We conclude that PAX3::MAML3 is a novel variant fusion of ARMS, which displays a methylation signature distinct from BSNS despite sharing similar PAX3 fusions. These findings highlight the utility of methylation profiling in classifying ARMS with non-canonical fusions.
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Bizarre parosteal osteochondromatous proliferation (BPOP) is a benign but rare periosteal-originating chondrogenic tumor. It commonly arises from the hands and feet. It is slow-growing and often presents as a painless lump. On imaging, the mass is well-marginated and almost always remains contiguous with the cortical bone. Histologically, the lesion is composed of a disorganized admixture of fibrous tissue, bone, and cartilage with bizarre features. Treatment is surgical and local recurrence is common contiguous with bone. This case report demonstrates an uncommon acromial BPOP with the first reported recurrence not contiguous with the underlying cortex.
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Background: Cranial fasciitis (CF) is a benign (myo)fibroblastic proliferation of children. Typical presentation consists of a rapidly growing solitary mass on the temporal or parietal cranium in the first 2 years of age. CF is characterized by a rapid growth followed by a relative slowdown and even growth arrest. The finding of somatic USP6 gene rearrangements demonstrating clonality in CF together with its clinical behavior places it in the category of diseases recently termed "transient neoplasia."Methods: Histological, immunohistochemical, and molecular findings of 18 patients with CF were retrospectively studied.Results: The tumor typically presented as a painless rapidly enlarging mass in the temporal region. Sixty-six percent of the cases harbored USP6 gene rearrangement. Nine patients were treated with gross total resection (GTR) and 9 with subtotal tumor resection (STR). Two patients treated with GTR had recurrence. Five patients treated with STR had progression-free disease for at least 10 months after surgery and in four patients the tumor regressed spontaneously a median 16 months after surgery.Conclusions: In this largest series to date, we reported the clinicopathological, immunohistochemical, and molecular findings of 18 pediatric cases of CF with emphasis on the clinical growth pattern of these tumors.
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Fasciite , Doenças Musculares , Neoplasias , Criança , Fasciite/genética , Fasciite/patologia , Rearranjo Gênico , Humanos , Doenças Musculares/genética , Neoplasias/genética , Estudos Retrospectivos , Ubiquitina Tiolesterase/genéticaRESUMO
BACKGROUND/OBJECTIVES: SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), first described in December 2019, has infected more than 33 million people and claimed more than 1 million deaths worldwide. Rheumatic diseases are chronic inflammatory diseases, the prevalence and impact of which in COVID-19 patients are poorly known. We performed a pooled analysis of published data intending to summarize clinical presentation and patient outcomes in those with established rheumatic disease diagnosis and concurrent COVID-19. METHODS: PubMed and Google Scholar were searched to identify studies reporting data about rheumatic disease patients who were diagnosed with SARS-CoV-2 infection and published until July 22, 2020. Random-effects models were used to estimate the pooled incidence and rates of hospitalization, intensive care unit admission, and mortality among these patients, and interstudy heterogeneity was identified using I2 statistics with greater than 75% value indicating substantial interstudy variation. RESULTS: Twenty studies were included, giving a total sample size of 49,099 patients positive for SARS-CoV-2. Of 49,099 COVID-19 patients, a total of 1382 were also diagnosed with a rheumatic disease in the past. The random-effects pooled prevalence of COVID-19 among rheumatic disease patients was found to be 0.9%. The rates of hospitalization, intensive care unit admission, and mortality were 70.7%, 11.6%, and 10.2%, respectively. CONCLUSIONS: Although the prevalence of SARS-CoV-2 infection is not dramatically high in rheumatic disease patients, concurrent COVID-19 does seem to play a role in determining disease severity and outcomes to some extent. Further studies are needed to give conclusive evidence about whether this subset of the population is at a higher risk of COVID-19 and related outcomes compared with the population at large.
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COVID-19 , Doenças Reumáticas , Hospitalização , Humanos , Unidades de Terapia Intensiva , Doenças Reumáticas/diagnóstico , Doenças Reumáticas/epidemiologia , SARS-CoV-2RESUMO
Coronavirus disease 2019 (COVID-19) pandemic is a global health crisis. Very few studies have reported association between obesity and severity of COVID-19. In this meta-analysis, we assessed the association of obesity and outcomes in COVID-19 hospitalized patients. Data from observational studies describing the obesity or body mass index and outcomes of COVID-19 hospitalized patients from December 1, 2019, to August 15, 2020, was extracted following PRISMA guidelines with a consensus of two independent reviewers. Adverse outcomes defined as intensive care units, oxygen saturation less than 90%, invasive mechanical ventilation, severe disease, and in-hospital mortality. The odds ratio (OR) and 95% confidence interval (95% CI) were obtained and forest plots were created using random-effects models. A total of 10 studies with 10,233 confirmed COVID-19 patients were included. The overall prevalence of obesity in our study was 33.9% (3473/10,233). In meta-analysis, COVID-19 patient with obesity had higher odds of poor outcomes compared with better outcomes with a pooled OR of 1.88 (95% CI: 1.25-2.80; p = 0.002), with 86% heterogeneity between studies (p < 0.00001). Our study suggests a significant association between obesity and COVID-19 severity and poor outcomes. Our results findings may have important suggestions for the clinical management and future research of obesity and COVID-19.
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COVID-19/fisiopatologia , Mortalidade Hospitalar , Hospitalização/estatística & dados numéricos , Obesidade/complicações , Índice de Massa Corporal , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Obesidade/virologia , Estudos Observacionais como Assunto , Prevalência , Respiração Artificial/estatística & dados numéricosRESUMO
AIMS: Several morphologically overlapping (myo)fibroblastic neoplasms harbour USP6 fusions, including aneurysmal bone cysts, nodular fasciitis, myositis ossificans, cranial fasciitis, fibro-osseous pseudotumour of the digits, and cellular fibroma of the tendon sheath. USP6-induced neoplasms are almost universally benign and cured by local excision. We aim to highlight the diagnostic value of USP6 fusion detection in a series of aggressive-appearing paediatric myofibroblastic tumours. METHODS AND RESULTS: Three deep-seated, radiographically aggressive, and rapidly growing childhood myofibroblastic neoplasms were morphologically and molecularly characterised by USP6 break-apart fluorescence in-situ hybridisation (FISH), transcriptome sequencing, and targeted capture analysis. Each tumour occurred in the lower-extremity deep soft tissue of a child presenting with pain, limping, or a mass. In all three patients, imaging studies showed a solid mass that infiltrated into surrounding skeletal muscle or involved/eroded underlying bone. The biopsied tumours consisted of variably cellular myofibroblastic proliferations with variable mitotic activity that lacked overt malignant cytological features. FISH showed that all tumours had USP6 rearrangements. On the basis of these results, all three patients were treated with conservative excision with positive margins. The excised tumours had foci resembling nodular fasciitis, fibromatosis, and pseudosarcomatous proliferation. Next-generation sequencing revealed COL1A1-USP6 fusions in two tumours and a COL3A1-USP6 fusion in the third tumour. One tumour had a subclonal somatic APC in-frame deletion. No recurrence was observed during follow-up (8-40 months). CONCLUSION: We present a series of benign, but aggressive-appearing, USP6-rearranged myofibroblastic tumours. These deep-seated tumours had concerning clinical and radiographic presentations and did not fit into one distinct histological category. These cases highlight the diagnostic value of USP6 fusion detection to identify benign nondescript tumours of this group, especially those with aggressive features, to avoid overtreatment.
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Miofibroma/genética , Miofibroma/patologia , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/patologia , Ubiquitina Tiolesterase/genética , Criança , Pré-Escolar , Fasciite/genética , Fasciite/patologia , Feminino , Rearranjo Gênico , Humanos , Lactente , Masculino , Miosite Ossificante/genética , Miosite Ossificante/patologia , Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/genética , Periósteo/patologiaAssuntos
Neoplasias , Coativador 3 de Receptor Nuclear , beta Catenina , Criança , Humanos , beta Catenina/imunologia , beta Catenina/metabolismo , Biomarcadores Tumorais/genética , Núcleo Celular/genética , Núcleo Celular/metabolismo , Coativador 3 de Receptor Nuclear/genética , Fibroblastos/patologiaRESUMO
One-third of gastrointestinal stromal tumors (GISTs) that lack KIT or PDGFRA mutations show succinate dehydrogenase (SDH) mutations or promoter hypermethylation. Most SDH-deficient GISTs occur in the pediatric, adolescent, or young adult setting and have unique features including predilection for the stomach, multinodular plexiform architecture, epithelioid cytology, prominence of lymphovascular invasion, and predilection for nodal metastasis. Dedifferentiation in GIST is a rare histologic change which may occur de novo or secondary to imatinib therapy and is characterized by abrupt transition of well-differentiated (WD) GIST to a subclonal anaplastic process that shows loss of immunohistochemical marks (CD117, DOG1). We describe the case of a previously healthy 18-year-old man who presented with a large gastric wall mass that contained 2 distinct morphologic populations. The first was WD and characterized by sweeping fascicles of bland spindled cells. This population abruptly transitioned to dedifferentiated (DD) foci composed of large sheets of discohesive cells that displayed a spectrum of rhabdoid and epithelioid morphologies with marked pleomorphism and mitotic activity. Immunohistochemically, the tumor showed variable staining in the 2 components with diffuse DOG-1 and CD117 positivity in the WD component and complete absence in the DD foci. SDH-B staining was lost in both components. Whole exome and transcriptome analysis was performed on tissue from both components and both showed an SDHB mutation (c.286G>A) as well as unique mutational burden and copy number profiles. Herein, we describe the first case of a DD SDH-deficient GIST with morphologic, immunophenotypic, and molecular characterization.
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Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/patologia , Succinato Desidrogenase/genética , Adolescente , Biomarcadores Tumorais/análise , Desdiferenciação Celular , Neoplasias Gastrointestinais/genética , Tumores do Estroma Gastrointestinal/genética , Humanos , Imuno-Histoquímica , Imunofenotipagem , Masculino , Succinato Desidrogenase/deficiênciaRESUMO
Shotgun metagenomic analysis of the human associated microbiome provides a rich set of microbial features for prediction and biomarker discovery in the context of human diseases and health conditions. However, the use of such high-resolution microbial features presents new challenges, and validated computational tools for learning tasks are lacking. Moreover, classification rules have scarcely been validated in independent studies, posing questions about the generality and generalization of disease-predictive models across cohorts. In this paper, we comprehensively assess approaches to metagenomics-based prediction tasks and for quantitative assessment of the strength of potential microbiome-phenotype associations. We develop a computational framework for prediction tasks using quantitative microbiome profiles, including species-level relative abundances and presence of strain-specific markers. A comprehensive meta-analysis, with particular emphasis on generalization across cohorts, was performed in a collection of 2424 publicly available metagenomic samples from eight large-scale studies. Cross-validation revealed good disease-prediction capabilities, which were in general improved by feature selection and use of strain-specific markers instead of species-level taxonomic abundance. In cross-study analysis, models transferred between studies were in some cases less accurate than models tested by within-study cross-validation. Interestingly, the addition of healthy (control) samples from other studies to training sets improved disease prediction capabilities. Some microbial species (most notably Streptococcus anginosus) seem to characterize general dysbiotic states of the microbiome rather than connections with a specific disease. Our results in modelling features of the "healthy" microbiome can be considered a first step toward defining general microbial dysbiosis. The software framework, microbiome profiles, and metadata for thousands of samples are publicly available at http://segatalab.cibio.unitn.it/tools/metaml.
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Microbioma Gastrointestinal/genética , Aprendizado de Máquina , Metagenoma/genética , Metagenômica/métodos , Neoplasias Colorretais/genética , Biologia Computacional/métodos , Humanos , Doenças Inflamatórias Intestinais/genética , Obesidade/genética , SoftwareRESUMO
Enterobius vermicularis is a common intestinal nematode; however, rare extraintestinal Enterobius infections have been reported from different parts of the world. Here, we present a case of tubo-ovarian abscess in an otherwise healthy young sexually active female with no known comorbids with history of on and off lower abdominal pain for one year and high grade fever for one month. On the basis of further workup and radiological evaluation, a preoperative diagnosis of right sided tubo-ovarian abscess was made and salpingo-oophorectomy was performed laproscopically in July 2015. Histopathology of the resected tissue revealed necrosis and in one area Enterobius vermicularis was identified surrounded by neutrophils and eosinophil rich abscess. A final diagnosis of severe acute and chronic salpingo-oophoritis with abscess formation, secondary to Enterobius vermicularis was made. Signs and symptoms of parasitic involvement in tubo-ovarian abscesses are not much different than usual presentations of pelvic inflammatory diseases and identification of a parasite in a tubo-ovarian tissue sample is a rare clinical finding. A high index of suspicion on the part of histopathologist as well as clinician is important for timely diagnosis and effective management of such cases.
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Abscesso/parasitologia , Enterobíase/patologia , Ooforite/parasitologia , Salpingite/parasitologia , Dor Abdominal , Abscesso/patologia , Abscesso/cirurgia , Adulto , Animais , Enterobíase/cirurgia , Enterobius , Feminino , Humanos , Ooforite/patologia , Ooforite/cirurgia , Doença Inflamatória Pélvica/parasitologia , Doença Inflamatória Pélvica/patologia , Doença Inflamatória Pélvica/cirurgia , Salpingite/patologia , Salpingite/cirurgia , Salpingo-OoforectomiaRESUMO
BACKGROUND: Dengue is a mosquito born viral infection that has rapidly spread in the world particularly in Southeast Asia. The aim of this hospital based study was to see the demographic, clinical and laboratory characteristics in adults with dengue infection in Hazara region of Northern Pakistan. METHODS: This is a descriptive study. Clinical, laboratory and demographic information were collected from adult patients with suspected dengue infection (n=100) and then managed in one of medical units of tertiary care hospital in Abbottabad from August to October 2015. RESULTS: Total number of patients was 100, 78 were male and 22 were female. 49 patients were in age group from 21 to 40 years. Most patients were from Mansehra district (69), followed by Haripur (11), Abbottabad (11), Battagram (06) and Kohistan (03). Common clinical features were fever (100%), body aches (95%), headache (94%), chills (87%), and anorexia (86%), haemorrhagic tendencies (12%), rash (05%), and sore throat (03%). Thrombocytopenia was observed in 98%, leucopoenia in 25%, high Aminotransferases (ALT) in 67%, Ns1 antigen positive 66%, negative 18% and unknown 16%. IgM Antibodies against Dengue Virus was positive 67%, negative 19% and were unknown in 14%, IgG antibodies positive in 54%, negative 32% and were unknown in 14%. CONCLUSIONS: We concluded in our study that presentation of dengue infection is same as in other Southeast Asian countries; however, the disease is more prevalent in cities located on plain than hilly areas.
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Dengue/diagnóstico , Leucopenia/etiologia , Trombocitopenia/etiologia , Adolescente , Adulto , Dengue/complicações , Dengue/epidemiologia , Feminino , Humanos , Incidência , Leucopenia/epidemiologia , Masculino , Pessoa de Meia-Idade , Paquistão/epidemiologia , Prevalência , Trombocitopenia/epidemiologia , Adulto JovemRESUMO
PROBLEM: Systems-based practice focuses on the organization, financing, and delivery of medical services. The American Association of Medical Colleges has recommended that systems-based practice be incorporated into medical schools' curricula. However, experiential learning in systems-based practice, including practical strategies to improve the quality and efficiency of clinical care, is often absent from or inconsistently included in medical education. INTERVENTION: A multidisciplinary clinician and nonclinician faculty team partnered with a cardiology outpatient clinic to design a 9-month clerkship for 1st-year medical students focused on systems-based practice, delivery of clinical care, and strategies to improve the quality and efficiency of clinical operations. The clerkship was called the Action Research Program. In 2013-2014, 8 trainees participated in educational seminars, research activities, and 9-week clinic rotations. A qualitative process and outcome evaluation drew on interviews with students, clinic staff, and supervising physicians, as well as students' detailed field notes. CONTEXT: The Action Research Program was developed and implemented at the University of California, San Francisco, an academic medical center in the United States. All educational activities took place at the university's medical school and at the medical center's cardiology outpatient clinic. OUTCOME: Students reported and demonstrated increased understanding of how care delivery systems work, improved clinical skills, growing confidence in interactions with patients, and appreciation for patients' experiences. Clinicians reported increased efficiency at the clinic level and improved performance and job satisfaction among medical assistants as a result of their unprecedented mentoring role with students. Some clinicians felt burdened when students shadowed them and asked questions during interactions with patients. Most student-led improvement projects were not fully implemented. LESSONS LEARNED: The Action Research Program is a small pilot project that demonstrates an innovative pairing of experiential and didactic training in systems-based practice. Lessons learned include the need for dedicated time and faculty support for students' improvement projects, which were the least successful aspect of the program. We recommend that future projects aiming to combine clinical training and quality improvement projects designate distinct blocks of time for trainees to pursue each of these activities independently. In 2014-2015, the University of California, San Francisco School of Medicine incorporated key features of the Action Research Program into the standard curriculum, with plans to build upon this foundation in future curricular innovations.
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Cardiologia/educação , Estágio Clínico , Educação de Graduação em Medicina/tendências , Aprendizagem Baseada em Problemas , Currículo , Feminino , Humanos , Entrevistas como Assunto , Masculino , Mentores , Desenvolvimento de Programas , Avaliação de Programas e Projetos de Saúde , Melhoria de Qualidade , Estados UnidosRESUMO
Background. Lipomas are common superficial soft tissue tumors of mature adipocytes. In contrast, well-differentiated/dedifferentiated liposarcoma typically presents in the retroperitoneum as large masses. We provide clinicopathologic and follow-up details of 9 retroperitoneal/intra-abdominal benign lipomatous tumors (BLT) and discuss the utility of ancillary fluorescence in situ hybridization (FISH) in distinguishing from their malignant counterparts. Design. Clinicopathologic details and histology of 9 intra-abdominal and retroperitoneal lipomas were studied along with ancillary CD10 immunohistochemistry (IHC) and FISH for MDM2 and CDK4 amplification. Results. There were 6 females and 3 males. Median age at diagnosis was 52 years (range 36-81 years). Seven were identified incidentally and 2 presented with primary complaints. On imaging, 7 were considered suspicious for liposarcoma. Grossly, the tumors ranged from 3.4 to 41.2â cm (median 16.5â cm). Histologically, all cases showed well-differentiated BLT, further classified as lipoma (n = 7; 1 with metaplastic ossification, 2 with prominent vessels, and 4 ordinary lipomas) and lipoma-like hibernoma (n = 2)-the latter 2 showed intramuscular lesions with interspersed brown fat. CD10 IHC showed strong staining in the 2 hibernomas, whereas the staining was weak in the remaining. MDM2 and CDK4 amplification were negative by FISH in all. Follow-up (median 18 months) did not show recurrence on clinical or imaging evaluation. Conclusion. Retroperitoneal/intra-abdominal BLT are extremely rare and are indistinguishable clinically and radiographically from liposarcoma. This necessitates molecular confirmation even when the histology is convincingly benign, for a confident diagnosis. Our cohort shows that conservative excision without removal of abutted organs is sufficient in most cases.
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Lipoma , Lipossarcoma , Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Hibridização in Situ Fluorescente/métodos , Proteínas Proto-Oncogênicas c-mdm2/genética , Quinase 4 Dependente de Ciclina/genética , Biomarcadores Tumorais , Lipossarcoma/diagnóstico , Lipossarcoma/genética , Lipoma/diagnóstico , Lipoma/genética , Lipoma/patologiaRESUMO
ISLET-1 (ISL1) is a LIM-homeodomain transcription factor. Selective ISL1 expression is shown in neuroendocrine, non-neuroendocrine, and some soft tissue tumors including desmoplastic small round cell tumor (DSRCT). We assessed the specificity of ISL1 (clone EP283, 1:500, Cell Marque) in 288 soft tissue tumors, which included 17 DSRCTs and other histologic mimics. Positive staining threshold for ISL1 was set to >10â¯% of neoplastic cell nuclei at moderate intensity. ISL1 IHC was positive in 15/16 (94â¯%) DSRCTs with 75â¯% showing diffuse (>50â¯%) expression. ISL1 was positive in 1/10 (10â¯%) Ewing sarcomas (EWS), 7/13 (54â¯%) alveolar rhabdomyosarcoma (RMS), 14/22 (63â¯%) embryonal RMS, 7/14 (50â¯%) synovial sarcomas, 15/16 (93â¯%) neuroblastoma, 1/5 (20â¯%) Wilms tumor, 2/4 (50â¯%) olfactory neuroblastoma, and all 9 Merkel cell carcinomas. Other tumors, including all CIC::DUX4 sarcomas, were negative except 3/27 leiomyosarcomas, and 1 each of angiosarcoma, myxoid liposarcomas, inflammatory myofibroblastic tumor, malignant peripheral nerve sheath tumor, tenosynovial giant cell tumor, dedifferentiated LPS, and 1 ectomesenchymoma. In summary, among the soft tissue tumors tested, ISL1 is a highly sensitive but moderately specific marker for DSRCT and may be useful to distinguish from round cell mimics including EWS and CIC::DUX4 sarcomas. The oncogenic role of ISL1 in these tumors warrants further investigation.
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Biomarcadores Tumorais , Tumor Desmoplásico de Pequenas Células Redondas , Proteínas com Homeodomínio LIM , Neoplasias de Tecidos Moles , Fatores de Transcrição , Humanos , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Tumor Desmoplásico de Pequenas Células Redondas/patologia , Tumor Desmoplásico de Pequenas Células Redondas/diagnóstico , Tumor Desmoplásico de Pequenas Células Redondas/metabolismo , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/metabolismo , Proteínas com Homeodomínio LIM/metabolismo , Proteínas com Homeodomínio LIM/análise , Fatores de Transcrição/metabolismo , Fatores de Transcrição/análise , Sensibilidade e Especificidade , Imuno-HistoquímicaRESUMO
We report the first description of spinal cord mycobacterial spindle cell pseudotumor. A patient with newly diagnosed advanced HIV presented with recent-onset bilateral leg weakness and was found to have a hypermetabolic spinal cord mass on structural and molecular imaging. Biopsy and cultures from blood and cerebrospinal fluid confirmed spindle cell pseudotumor due to Mycobacterium avium-intracellulare. Despite control of HIV and initial reduction in pseudotumor volume on antiretrovirals and antimycobacterials (azithromycin, ethambutol, rifampin/rifabutin), he ultimately experienced progressive leg weakness due to pseudotumor re-expansion. Here, we review literature and discuss multidisciplinary diagnosis, monitoring and management challenges, including immune reconstitution inflammatory syndrome.
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Infecção por Mycobacterium avium-intracellulare , Humanos , Masculino , Infecção por Mycobacterium avium-intracellulare/diagnóstico , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Infecção por Mycobacterium avium-intracellulare/diagnóstico por imagem , Doenças da Medula Espinal/diagnóstico por imagem , Doenças da Medula Espinal/tratamento farmacológico , Doenças da Medula Espinal/microbiologia , Adulto , Infecções por HIV/complicaçõesRESUMO
BACKGROUND: Ehlers-Danlos syndrome (EDS) may be linked to dysfunction in the autonomic nervous system, affecting collagen production and processing. These collagen abnormalities lead to a condition called dysautonomia. Findings underscore the need for further investigation into autonomic nervous system function in EDS which involves larger studies to strengthen the evidence of non-invasive screening tools like cardiovascular reflex tests. These tests might offer a valuable way to assess an individual's risk for future complications. OBJECTIVE: This study aimed to assess autonomic reactivity in EDS patients using cardiovascular reflex tests. METHODS: This study was conducted at the Department of Physiology, Naraina Medical College and Research Centre, Kanpur (Uttar Pradesh). The cardiovascular reflex test was used to identify 60 individuals, 30 of whom were EDS patients and 30 were healthy controls, with a common age limit of 18-25 years. Cardiovascular reflex tests, such as the delta heart rate, lying-to-standing test (LST), deep breathing test (DBT), and Valsalva maneuver, were performed and recorded for each subject. IBM SPSS Statistics for Windows, Version 21.0 (Released 2012; IBM Corp., Armonk, New York, United States) was used for the compilation and analysis of data. RESULTS: The expiration-to-inspiration (E:I) ratio and delta heart rate of the EDS patients both significantly decreased as compared to the healthy control group (1.10±0.02 versus 1.22±0.77 and 14.03±0.31 versus 15.52±0.32). The Valsalva ratio of the EDS patients decreased (1.28±0.01) as compared to the healthy control group (1.46±0.01), which was statistically significant. The 30:15 ratio in the EDS patients was significantly decreased compared to the healthy control group (1.08±0.01 versus 1.15±0.01). The handgrip test and cold pressor test results were statistically insignificant. CONCLUSION: The study suggests a connection between EDS and autonomic nervous system dysfunction, causing symptoms like tachycardia and hypotension. It recommends exploring non-invasive cardiovascular reflex tests as a tool to identify autonomic dysfunction in EDS patients and predict long-term cardiovascular complications. These tests offer valuable insights into autonomic function.
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Different authors have recently described a subtype of lipoma characterized by variation of adipocyte size, single cell fat necrosis, and a subset with minimal to mild nuclear atypia, and termed these as anisometric cell/dysplastic lipoma (AC/DL). These lipomas follow a benign course and rarely recur. In 3 examples, AC/DL has occurred in patients with childhood retinoblastoma (RB). We report another such example where multiple AC/DL occurred in the neck and back of a 30-year-old male who had germline RB1 gene deletion and bilateral RB in infancy. On excision, all tumors histologically showed similar morphology of adipocyte anisometry, focal single cell necrosis with surrounding binucleated or multinucleated histiocytes, hyperchromatic and minimally atypical lipocyte nuclei, vacuolated Lockhern change, rare foci of fibromyxoid change, occasional mononuclear cell clusters around capillaries, and loss of RB1 immunostaining. Unequivocal atypical cells, lipoblasts, floret-nucleated or multinucleated giant cells were absent. Molecular analysis of tumor cells showed monoallelic RB1 gene loss without amplification of MDM2 and CDK4 genes. Short-term follow up did not show tumor recurrence. AC/DLs in RB survivors are characterized by multiplicity, unifying histology, and benign course. Their biology appears distinct from ordinary lipomas, spindle cell lipomas, and atypical lipomatous tumors.
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Lipoma , Lipossarcoma , Neoplasias da Retina , Retinoblastoma , Neoplasias de Tecidos Moles , Masculino , Humanos , Criança , Adulto , Retinoblastoma/genética , Neoplasias de Tecidos Moles/patologia , Biomarcadores Tumorais/análise , Lipoma/genética , Lipoma/patologia , Lipossarcoma/patologia , HiperplasiaRESUMO
Islet-1 (ISL1) plays key roles in programming the epigenome and facilitating the recruitment of additional regulatory factors. Although it has been used as a marker for pancreatic neuroendocrine tumors (PanNETs), ISL1 reactivity in other tumor types are critically missing. ISL1 immunohistochemistry was performed on 147 neuroendocrine tumors (NET) originated in pancreas, gastrointestinal tract, lung, thyroid, parathyroid, pituitary, adrenal medulla, head/neck, genitourinary tract, and skin; and 110 non-neuroendocrine tumors originated in the pancreas, thymus, lung, thyroid, mesothelium, adrenal cortex, stomach, breast, head/neck, skin, and kidney. ISL1 nuclear staining was observed in normal thymic epithelium, pancreatic islets, adrenal medulla, and pituitary gland cells as well as frequently in tumors of these origins: pancreatic NET (78%), paraganglioma/pheochromocytoma (100%), thymoma (82%), and pituitary NET (50%). ISL1 was also variably expressed in certain non-pancreatic NET such as Merkel cell carcinoma (100%), medullary carcinoma of the thyroid (100%), head/neck NEC (80%), genitourinary NEC (71%), lung small cell carcinoma (46%), lung carcinoids (17%), lower intestinal tract NET (93%) but not in upper gastrointestinal tract NET nor parathyroid adenoma. For other non-NETs, focal ISL1 expression was less frequently detected in gastric adenocarcinoma (40%), mesothelioma (29%), adrenal cortical carcinoma (17%), and squamous carcinoma (24%), but not in others tested. ISL1 is not a pan-NE marker as it is consistently lacking in upper gastrointestinal NET and parathyroid adenoma. It is also differentially expressed in thymoma. ISL1 immunohistochemnistry could help to differentiate PanNET and lower intestinal NET from upper gastrointestinal NET and be used as a marker for thymoma.
Assuntos
Neoplasias Gastrointestinais , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Neoplasias das Paratireoides , Neoplasias Cutâneas , Timoma , Neoplasias do Timo , Humanos , Biomarcadores Tumorais/metabolismo , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/patologia , Neoplasias Gastrointestinais/patologia , Neoplasias Pancreáticas/patologiaRESUMO
OBJECTIVES: Granular cell tumor (GCT) commonly presents in the subcutaneous tissue and head and neck region, and it is uncommon in the gastrointestinal tract. Experience with esophageal GCTs in the pediatric population is limited, with only 7 cases reported in the literature, 3 with eosinophilic esophagitis (EoE). METHODS: Case information from 11 pediatric patients with GCTs of the esophagus was retrieved. H&E and immunohistochemical slides were reviewed with clinical, endoscopic, and follow-up data from all patients. RESULTS: In total, 7 male and 4 female patients were included, with ages ranging from 3 to 14 years. Indications for esophagogastroduodenoscopy (EGD) included EoE (n = 3), follow-up for Crohn disease, and other nonspecific complaints. Endoscopically, all patients had a single submucosal, firm mass protruding into the lumen, with normal overlying mucosa. The nodules were removed endoscopically in multiple fragments in all cases. Histologically, the tumors showed sheets and trabeculae of cells containing bland nuclei, inconspicuous nucleoli, and abundant pink granular cytoplasm without atypical features. All tumors were immunoreactive for S100, CD68, and SOX10. Follow-up showed that all patients were disease-free (median, 2 years). CONCLUSIONS: We report the largest series of pediatric esophageal GCTs with coincidental association with EoE. These EGD findings are characteristic, and removal by biopsy is both diagnostic and therapeutic.