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INTRODUCTION AND IMPORTANCE: Placental non-trophoblastic tumors (PNTT) are uncommon, consisting mainly of chorangiomas, placental teratomas (PT) and haemangiomas. PT are exceedingly rare, with less than 40 cases reported in the literature. We, herein, present a case of mature PT arising within the membranes, and we aim to discuss the clinico-pathological characteristics of this rare entity. CASE PRESENTATION: A 30-year-old female patient, gravida 1, para 1, with no medical history, was admitted at 40 weeks' gestational age. Ultrasound in the third trimester of pregnancy revealed agenesis of the left fetal kidney and a fundal placenta with increased uterine artery resistance. A cesarean section was performed for failure of labor's induction. Gross examination of the placenta revealed a solid polypoid mass, measuring 4 × 2 cm, attached to the membranes and covered by a smooth cutaneous coating. The cut surface was soft, yellowish, and focally heterogenous, with areas of adipose tissue and cartilage. Microscopic examination revealed that the mass was made up of a mature keratinized squamous layer, with skin appendages, adipose and cartilaginous tissues. The diagnosis of PT was established. CLINICAL DISCUSSION: PT are rarely suspected on prenatal ultrasonography and the diagnosis is made after delivery. Only pathological examination allows the diagnosis of certainty. Their histogenesis is still poorly understood. CONCLUSION: We presented a rare case of mature PT arising within the membranes. PT are extremely uncommon tumors. Usually, they are benign, and no fetal or maternal complications. A better knowledge of these uncommon tumors is mandatory to not miss the diagnosis.
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INTRODUCTION: The progression of prostate cancer (PCa) has been linked worldwide, including in African populations, to the dysregulation of the epithelial-mesenchymal transition (EMT). METHODS: To clarify the connection among EMT markers, clinicopathological parameters, and epidemiological factors, we analyzed 35 PCa specimens from patients in Tunisia, a country in North Africa, arranged by stages. We also carried out extensive molecular and epidemiological analyses. RESULTS: Significant dysregulation of EMT genes was found, with an overexpression of ZEB-1, Twist, Snail-1, and Vimentin (p < 0.05) and underexpression of E-cadherin and ß-catenin (p < 0.05). Positive correlations were observed between transcription factors and the mesenchymal marker Vimentin (p < 0.001, r = 0.574; p = 0.029, r = 0.411; and p < 0.001; r = 0.506) according to Spearman correlation analyses, whereas negative correlations were found between epithelial markers (E-cadherin, ß-catenin) and Vimentin (p < 0.05; r < 0). Higher PSA, Gleason scores, and metastasis were all correlated with the dysregulation of EMT (p < 0.05). Notably, there was a positive correlation between higher consumption of tobacco (≥20 Packets per year) and Vimentin expression (p < 0.001, r = 0.854), suggesting a relationship between smoking and EMT activation in the Tunisian population. Moreover, Twist showed a positive correlation with diabetes (p < 0.001, r = 0.385), whereas no significant correlations were found between EMT markers and comorbidities such as hypertension and coronary insufficiency. These results demonstrate the intricate connection between molecular changes, epidemiological factors, and disease progression, and they emphasize the crucial role that EMT plays in promoting PCa aggressiveness in African populations, particularly in Tunisia. CONCLUSION: In summary, understanding these correlations could help develop focused treatment plans and enhance patient outcomes for PCa management in African settings.
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Currently, clinical biomarkers are urgently needed to improve patient management to guide personal therapy for cancer. In this study, we investigate the deregulation of Zeb-1 in prostate cancer (PC) Tunisian patients. Expression patterns of the Zeb-1 were investigated in prostate adenocarcinoma and benign prostate biopsies using quantitative real-time reverse transcription-polymerase chain reaction (RT-qPCR) and 2-ΔΔCt method. Statistical analysis was used to identify differences across groups depending on gene expression level. Furthermore, we exploited a follow-up over 15 years to correlate Zeb-1 deregulation and clinical outcomes in PC patients. Based on ROC curve analyses, the AUC was found in discriminating PC patients from controls (AUC = 0.757; p < 0.001). In addition, the higher expression level was significantly associated with PSA, Digital Rectal Examination, Gleason score, tumor stage, and distant lymph node metastases. Moreover, Zeb-1 overexpression was correlated with shorter overall survival (OS) (p = 0.042), poor progression-free survival (PFS) (p = 0.007), and with resistance to taxanes (p = 0.012). Our data provide the aberrant expression of Zeb-1 in PC patients suggesting its potential diagnostic, prognostic, and theranostic role. Further functional studies are mandatory to strengthen these results and to uncover the molecular mechanism of this neoplasm. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-03941-8.
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BACKGROUND: Prostate cancer (PCa) remains one of the most complex tumors in men. The assessment of gene expression is expected to have a profound impact on cancer diagnosis, prognosis, and treatment decisions. The aim of this study was to determine the utility of the epithelial-mesenchymal transition (EMT) transcription factors Twist and Snai1 in the treatment of naïve prostate cancer. METHODS AND RESULTS: We analyzed formalin-fixed paraffin-embedded (FFPE) prostate tissues from 108 PCa patients and 20 control biopsies using real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and 2-ΔΔCt methods for Twist and Snail gene expression. The expression of Twist and Snai1 mRNA was significantly overexpressed in primary tissues of PCa patients compared with controls using ROC curve. Statistical analysis showed that the mRNAs of these two genes expression Snai1 and Twist were positively correlated with tumor development and prognostic parameters as Gleason score (p < 0.001; r = 0.707) and (p < 0.001; r = 0.627) respectively. The results of Kaplan-Meier analysis showed that mRNA expression of Snai1 and Twist genes expression were significant predictors of poor overall survival (OS) (Log rank p < 0.001) and progression-free survival (PFS) of patients (Log rank p < 0.001). Furthermore, our results showed that the expression of Snai1 and Twist genes expression in primary tissues of PCa patients could predict resistance to androgen deprivation therapy (p < 0.001) and resistance to the acidic drugs abiraterone or enzalutamide (p < 0.001). However, these two transcription factors failed to predict taxanes resistance at the time of diagnosis (p > 0.05). CONCLUSION: These results suggest that Snai1 and Twist are overexpressed during the onset and progression of PCa malignancies and may be theranostic markers of resistance to ADT, abiraterone, or enzalutamide therapy.
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Benzamidas , Nitrilos , Feniltiohidantoína , Neoplasias de la Próstata , Factores de Transcripción de la Familia Snail , Proteína 1 Relacionada con Twist , Humanos , Masculino , Antagonistas de Andrógenos , Benzamidas/uso terapéutico , Biomarcadores de Tumor/genética , Nitrilos/uso terapéutico , Feniltiohidantoína/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/genética , ARN Mensajero/genética , Proteína 1 Relacionada con Twist/genética , Factores de Transcripción de la Familia Snail/genéticaRESUMEN
Although epithelial-mesenchymal markers play an important role in prostate cancer (PC), further research is needed to better understand their utility in diagnosis, cancer progression prevention, and treatment resistance prediction. Our study included 111 PC patients who underwent transurethral resection, as well as 16 healthy controls. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to examine the expression of E-cadherin, ß-catenin, and Vimentin. We found that E-cadherin and ß-catenin were underexpressed in primary PC tissues. E-cadherin expression was found to be inversely associated with prostate-specific antigen progression (PSA-P; serum marker of progression; p = 0.01; |r| = 0.262). Furthermore, the underexpression of two markers, E-cadherin and ß-catenin, was found to be associated with advanced tumor stage and grade (p < 0.05). On the other hand, Vimentin was overexpressed in PC patients with a fold change of 2.141, and it was associated with the diagnosis, prognosis, and prediction of treatment resistance to androgen deprivation therapy (p = 0.002), abiraterone-acid (p = 0.001), and taxanes (p = 0.029). Moreover, the current study highlighted that poor survival could be significantly found in patients who progressed after primary surgery, did not use drugs, and expressed these genes aberrantly. In Cox regression multivariate analysis (p < 0.05), a positive correlation between the Vimentin marker and coronary heart disease in PC patients was identified (p = 0.034). In summary, the present study highlights the diagnostic (p < 0.001), prognostic (p < 0.001), and therapeutic potential of Vimentin in primary PC (p < 0.05), as well as its implications for cardiovascular disease. Furthermore, we confirm the potential prognostic value of E-cadherin and ß-catenin.
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Neoplasias de la Próstata , beta Catenina , Masculino , Humanos , beta Catenina/genética , Vimentina/genética , Vimentina/análisis , Vimentina/metabolismo , Antagonistas de Andrógenos , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Cadherinas/genética , Transición Epitelial-MesenquimalRESUMEN
IMPORTANCE: Cervical tuberculous lymphadenitis (CTL), the most frequent extrapulmonary form of tuberculosis, is currently a major health problem in Tunisia and in several regions around the world. CTL diagnosis is challenging mainly due to the paucibacillary nature of the disease and the potential misdiagnosis as cervical non-tuberculous lymphadenitis. This study demonstrates the added value of the heparin-binding hemagglutinin-interferon-gamma release assay as an immunoassay in the context of CTL.
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Antineoplásicos , Mycobacterium tuberculosis , Tuberculosis Ganglionar , Humanos , Ensayos de Liberación de Interferón gamma , Tuberculosis Ganglionar/diagnóstico , TúnezRESUMEN
Constitutional mismatch repair deficiency (CMMRD) syndrome is a rare autosomal recessive genetic disorder caused by biallelic germline mutations in one of the mismatch repair genes. Carriers are at exceptionally high risk for developing, typically in early life, hematological and brain malignancies, as well as cancers observed in Lynch syndrome. We report a homozygous MLH1 missense variant (c.1918C>A p.(Pro640Thr)) in a Tunisian patient with CMMRD syndrome and a family history of early-age colorectal cancer. The proband presented initially with colonic oligopolyposis and adenosquamous carcinoma of the caecum. He later developed several malignancies, including undifferentiated carcinoma of the parotid, grade 4 IDH-mutant astrocytoma, and ampulla of Vater adenocarcinoma. The patient was older than typical for this disease and had a remarkably prolonged survival despite developing four distinct aggressive malignancies. The current report highlights the challenges in assessing the pathogenicity of the identified variant and the remarkable phenotypic diversity in CMMRD.
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Key clinical message: We report the first case of pathologic complete response (pCR) to neoadjuvant imatinib in a gastric stromal tumor harboring KIT mutations in both exons 11 and 9. The significance of this co-occurrence is unknown and might increase the responsiveness of gastrointestinal stromal tumors (GISTs) to imatinib. Abstract: pCR of GIST to neoadjuvant imatinib is rare. We report a case of pCR to neoadjuvant imatinib in a gastric stromal tumor that harbored co-occurrence of multiple KIT mutations in exons 11 and 9. This co-occurrence in exons 9 and 11 is the first to be reported in the English literature.
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BACKGROUND: Lupus nephritis and lupus erythematosus tumidus (LET) are uncommon manifestations of systemic lupus erythematosus (SLE), and their coexistence as the initial presentation of SLE is exceedingly rare. Here, we report such a case, emphasizing the diagnostic challenges and therapeutic implications of this unusual association. CASE REPORT: A 38-year-old North African woman presented in Nephrology department with a history of lower extremity edema, fatigue, and weight loss of 3 kg in 4 weeks. Physical examination revealed LET lesions on the chest and the Neck. Laboratory investigations showed lymphopenia, low C3 and C4 complement levels, positive antinuclear antibodies, anti-dsDNA antibodies, and anti-SSA/Ro antibodies. Renal function tests showed normal serum creatinine and nephrotic proteinuria. Renal biopsy revealed Class V lupus nephritis. Skin biopsy confirmed the diagnosis of LET, with the presence of lymphohistiocytic infiltrates and dermal mucin. The patient was diagnosed with SLE based on the 2019 EULAR/ACR criteria and treated with prednisone (1 mg/kg/day) and hydroxychloroquine. She showed significant improvement in her cutaneous and renal symptoms at 6 and 12 months follow-up. CONCLUSION: The rarity of the coexistence of LET and lupus nephritis as the initial manifestation of SLE, especially in the North African population, underscores the need for further research to elucidate the immunopathogenic mechanisms and prognostic factors associated with this association.
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Lupus Eritematoso Discoide , Lupus Eritematoso Sistémico , Nefritis Lúpica , Adulto , Femenino , Humanos , Lupus Eritematoso Discoide/complicaciones , Lupus Eritematoso Discoide/diagnóstico , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Nefritis Lúpica/complicaciones , Nefritis Lúpica/diagnósticoRESUMEN
BACKGROUND: The aim of this study was to analyze PIK3CA mutations in exons 9 and 20 in breast cancers (BCs) and their association with clinicopathological characteristics. METHODS: Mutational analysis of PIK3CA exon 9 and 20 was performed by Sanger sequencing in 54 primary BCs of Tunisian women. The associations of PIK3CA mutations with clinicopathological characteristics were analyzed. RESULTS: Fifteen exon 9 and exon 20 PIK3CA variants were identified in 33/54 cases (61%). PIK3CA mutations including pathogenic (class 5/Tier I) or likely pathogenic (class 4/Tier II) occurred in 24/54 cases (44%): 17/24 cases (71%) in exon 9, 5/24 cases (21%) in exon 20 and 2/24 cases (8%) in both exons. Of these 24 cases, 18 (75%) carried at least one of the three hot spot mutations: E545K (in 8 cases), H1047R (in 4 cases), E542K (in 3 cases), E545K/E542K (in one case), E545K/H1047R (in one case) and P539R/H1047R (in one case). Pathogenic PIK3CA mutations were associated with negative lymph node status (p = 0.027). Age distribution, histological SBR tumor grading, estrogen and progesterone receptors, human epidermal growth factor receptor 2, and molecular classification were not correlated with PIK3CA mutations (p > 0.05). CONCLUSION: The frequency of somatic PIK3CA mutations in BCs of Tunisian women is slightly higher than that of BCs of Caucasian women and more observed in exon 9 than in exon 20. PIK3CA mutated status is associated with negative lymph node status. These data need to be confirmed in larger series.
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Neoplasias de la Mama , Femenino , Humanos , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Fosfatidilinositol 3-Quinasa Clase I/genética , MutaciónRESUMEN
Cerebral sinus thrombosis (CST) is an uncommon condition in children with a variable clinical presentation which has rarely been described in the setting of diabetic ketoacidosis. We present the case of 14-year-old child in whom lateral sinus thrombosis was caused by dehydration complicating ketoacidosis in a previously undiagnosed type 1 diabetes. The diagnosis of the CST was established during the autopsy due to the rapidity of the neurological deterioration. The cause of death was tonsillar herniation due to diffuse cerebral edema secondary to CST. This is the first published report of a CST in association with new onset type 1 diabetes in a child diagnosed at the postmortem examination.
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Edema Encefálico , Diabetes Mellitus Tipo 1 , Cetoacidosis Diabética , Trombosis de los Senos Intracraneales , Humanos , Niño , Adolescente , Cetoacidosis Diabética/complicaciones , Cetoacidosis Diabética/diagnóstico , Diabetes Mellitus Tipo 1/complicaciones , Trombosis de los Senos Intracraneales/complicaciones , Trombosis de los Senos Intracraneales/diagnóstico , Edema Encefálico/etiología , EncefaloceleRESUMEN
BACKGROUND: Breast cancer (BC) is the most frequent malignancy among women in Tunisia and Algeria. Clinical and pathological characteristics of this cancer among these populations are not widely reported. The aim of the study was to report clinical and pathological characteristics of women's BC in a Tunisian and Algerian series. METHODS: Pathologically confirmed 1089 BCs were gathered in the pathology departments of three Northern Tunisian hospitals: Tunis military, Charles Nicolle and Jendouba and in the pathology department of Alger Douera hospital between January 2015 and December 2020. Clinical and pathological findings of the two series: age, tumor size, histological type, grading according to Scarff-Bloom Richardson grading system, lymph node status at the time of diagnosis in axillary lymphadenectomy specimens and the immunohistochemical expression of estrogen and progesterone receptors (ER/PR), HER2 and Ki-67, were collected from the pathological reports. RESULTS: The median age at diagnosis was 50 and 48 years in Tunisian and Algerian series, respectively (p = 0.016). The diagnosis of BC was made on surgical specimens (lumpectomy or mastectomy) in 373/491 (76%) cases of the Tunisian series and in 225/598 (37.6%) cases of the Algerian one. Median tumor size was 2.8 cm and 2.5 cm in Algerian and Tunisian series, respectively (p = 0.252). Invasive BCs not otherwise specified was observed in 440/481 (91.5%) BCs in Tunisian series and in 519/586 (88.6%) BCs in Algerian series. Axillary lymph node positive tumors were observed in 64.6% and 58.8% of Tunisian and Algerian women, respectively (p = 0.926). BCs were ER positive in 311/385 (80.8%) and 486/571 (85.1%) cases and HER2 positive in 86/283 (30.4%) and 60/385 (15.6%) cases of Tunisian and Algerian series, respectively. CONCLUSIONS: In Tunisia and Algeria, BC has poor prognostic factors with large tumor sizes and high rates of lymph nodes involvement at diagnosis.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/patología , Túnez/epidemiología , Argelia/epidemiología , Pronóstico , Escisión del Ganglio Linfático , Ganglios Linfáticos/patología , Adulto , Persona de Mediana Edad , Adulto Joven , Anciano , Anciano de 80 o más AñosRESUMEN
Gitelman syndrome represents the clinical manifestations of inactivation of the Slc12a3 genes encoding the thiazide-sensitive sodium chloride cotransporter and the Trpm6-Mg genes encoding the magnesium transporters in the distal convoluted tubule. In fact, the biochemical findings resemble those with thiazide diuretics such as hypokalemia, hypomagnesaemia, hypocalciuria, metabolic alkalosis, and low normal blood pressure. He is usually associated with calcium pyrophosphate deposition. Serum uricemia level is rarely affected in Gitelman syndrome. We aimed to report a rare association of chronic gout with Gitelman syndrome, hence the interest of our case. We describe a 29-year-old male patient with a history of Gitelman syndrome associated with articular gout including pelvic localization. We provided pictorial evidence of extensive and diffuse monosodium urate deposition in articular and periarticular structures to confirm the gout origin. A literature review illustrates 4 reported cases of Gitelman syndrome associated with gout. The gender distribution was equal with a mean age of 40 years.
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Calcinosis , Síndrome de Gitelman , Gota , Hipopotasemia , Masculino , Humanos , Adulto , Síndrome de Gitelman/complicaciones , Síndrome de Gitelman/genética , Hipopotasemia/complicaciones , Hipopotasemia/genética , Magnesio , Gota/complicaciones , Miembro 3 de la Familia de Transportadores de Soluto 12RESUMEN
INTRODUCTION: Primary osseous Rosai-Dorfman disease (RDD) is a rare and benign disease that can pose diagnosis challenges. PRESENTATION OF THE CASE: We report the case of a 29-year-old woman who presented with pain in her left patellar region for the past 6 months with no other clinical sign especially no lymphadenopathy associated. A surgical excision was done. Histopathology confirmed the diagnosis of a primary RDD patellar disease. The patient was followed up for 2 months without any recurrence. The aim of this study was to present a rare case of RDD in a patellar location and to review clinicopathological features, therapeutic modalities, evolutionary aspects and prognosis of a primary patellar RDD. DISCUSSION AND CONCLUSION: The diagnosis of a primary osseous RDD without associated lymphadenopathy should be kept in mind when a sclero-lytic lesion is found. Excision of the lesion is the gold standard of the treatment.
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BACKGROUND: Several studies have interrogated the molecular pathways and their interacting genes underlying bladder cancer (BCa) tumorigenesis, yet, the role of homeobox genes is still poorly understood. Specifically, HOXA13, which plays an important role as a major actor in the urogenital tract's development. METHODS: Immunohistochemical (IHC) staining was performed to inspect the differential expression of HOXA13 protein in non-muscle-invasive bladder cancer (NMIBC) and non-tumoral tissues. A semiquantitative scoring system was adopted to evaluate the IHC labeling. Correlation to clinical parameters was performed by descriptive statistics. Overall survival was estimated by the Kaplan-Meier method and Cox regression model. The functional HOX A13 protein association networks (PPI) were obtained using String 11.0 database. RESULTS: HOX A13 exhibited cytoplasmic and nuclear staining. Its expression levels were lower in high-grade NMIBC (HG NMIBC) compared to low-grade ones (LG NMIBC). The expression of HOX A13 was correlated to tumor grade (LG/HG) (p = 0.036) and stage (TA/T1) (p = 0.036). Nevertheless, its expression was not correlated to clinical parameters and was not able to predict the overall survival of patients with HG NMIBC. Finally, PPI analysis revealed that HOX A13 seems to be a part of a molecular network holding mainly PBX1, MEIS, ALDH1A2, HOX A10, and HOX A11. CONCLUSION: The deregulation of HOX A13 is not associated with the prognosis of BCa. It seems to be rather implicated in the early initiation of urothelial tumorigenesis and thus may serve as a diagnostic marker in patients with NMIBC. Further experimentations on larger validation sets are mandatory.
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Neoplasias de la Vejiga Urinaria , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinogénesis , Humanos , Invasividad Neoplásica , Pronóstico , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
Melanotic lupus erythematosus (LE) is a rare and newly described form of chronic cutaneous LE. In this review, we have synthesized existing data on the epidemiologic, clinical, histologic, and immunologic features of melanotic LE. We performed a systematic review using PubMed to identify eligible publications. Eight contributions fulfilled the eligibility criteria and were included in the qualitative synthesis. Twenty-eight patients with a mean age of 57.7 years were included. All patients had medium to dark skin phototypes. The lesions presented either as solitary and localized, poorly limited, round, or oval patches (50%) or as a more diffuse or generalized, sometimes reticulated, hyperpigmentation (50%). Patients diagnosed with systemic LE accounted for 14% of included cases. Antinuclear antibodies were positive in 10.7% of cases. Hydroxychloroquine and topical steroids were the most commonly used treatments. Complete resolution of the lesions was noted in 27.27% of cases. No patient experienced atrophy, destruction, or deformity of the skin. Melanotic LE appears to affect mainly patients with dark phototypes. It is characterized by late age at the onset of disease and an overall good prognosis.
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Lupus Eritematoso Cutáneo , Lupus Eritematoso Discoide , Lupus Eritematoso Sistémico , Humanos , Persona de Mediana Edad , Lupus Eritematoso Cutáneo/diagnóstico , Lupus Eritematoso Cutáneo/tratamiento farmacológico , Lupus Eritematoso Discoide/diagnóstico , Lupus Eritematoso Discoide/tratamiento farmacológico , Lupus Eritematoso Discoide/epidemiología , Lupus Eritematoso Sistémico/diagnóstico , Piel/patología , Anticuerpos AntinuclearesRESUMEN
Cardiac echinococcosis is rare, and its clinical evolution is slow and asymptomatic until complications occur such as sudden death. Although more frequent in endemic countries, hydatid disease should be known by forensic specialists with regard to the migration flows of people from zones with high endemicity and who are likely to die from infection. We report an autopsy case of a 33-year-old male without any medical history who presented to the emergency room with shortness of breath, chest tightness, tingling all over the body and faintness without fever. He died suddenly before the medical examination. Autopsy showed no traumatic injuries or signs of violence. A cardiac 7 cm multivesicular hydatid cyst situated on the interventricular septum and the interatrial septum was observed. The cyst was ruptured with a massive hydatid pulmonary embolism. Hydatid cysts were also observed in the lungs. No signs of anaphylactic shock were found. The diagnosis of hydatid cyst was confirmed by histopathological examinations. Our case report highlights the mechanisms of occurrence of cardiac echinococcosis and hydatid pulmonary embolism as a complication, as well as the autopsy findings and the precautions needed by the forensic doctor.