Clinical Manifestations of Monkeypox.

Monkeypox is a global health issue caused by the monkeypox virus. It can spread from person to person through respiratory secretions, direct exposure to dermatological lesions of infected patients, or exposure to contaminated objects. It is more common in homosexual men, and most patients are asymptomatic. The gold standard for diagnosis is a real-time polymerase chain reaction. In the absence of testing facilities, clinicians rely upon detailed history to exclude other causes of fever with rashes. Initially, there is a prodrome phase of a few days, which is followed by the appearance of rashes. The dermatological manifestations are in the form of an exanthematous rash, which transforms through a macular, papular, and vesicular phase and disappears after crusting in approximately 3 weeks. There can be associated lymphadenopathy in these patients. Respiratory manifestations include nasal congestion and shortness of breath that may result in secondary bacterial infections. Additionally, patients can have neurological involvement in the form of encephalitis. Furthermore, ocular involvement can occur in the form of conjunctivitis, keratitis, and corneal ulceration. Other symptoms can include diarrhea, vomiting, myalgia, and backache. Since most patients do not require hospitalization, the approach to treatment is mainly vigilant monitoring, antiviral therapy, and management of associated complications.

Morphologic Spectrum of Lymphadenopathy in Adult-onset Immunodeficiency (Anti-interferon-γ Autoantibodies).

Adult-onset immunodeficiency syndrome (AOIS) caused by anti-interferon-γ autoantibodies is an emerging disease. Affected patients present typically with systemic lymphadenopathy, fatigue, and fever. We studied 36 biopsy specimens, 31 lymph nodes, and 5 extranodal sites, of AOIS confirmed by serum autoantibody or QuantiFERON-TB Gold In-Tube assay. We describe the morphologic features and the results of ancillary studies, including special stains, immunohistochemistry, and molecular testing. The overall median age of these patients was 60.5 years (range, 41 to 83 y) with a male-to-female ratio of 20:16. All biopsy specimens showed nontuberculous mycobacterial infection, and most cases showed the following histologic features: capsular thickening with intranodal sclerosing fibrosis, irregularly distributed ill-formed granulomas or histiocytic aggregates with neutrophilic infiltration, interfollicular expansion by a polymorphic infiltrate with some Hodgkin-like cells that commonly effaces most of the nodal architecture and proliferation of high endothelial venules. In situ hybridization analysis for Epstein-Barr virus-encoded RNA showed scattered (<1%) to relatively more common (4% to 5%) positive cells in 29 of 30 (97%) tested specimens, reflecting immune dysregulation due to an interferon-γ defect. In the 31 lymph node specimens, 23 (74%) cases showed increased immunoglobulin G4-positive plasma cells (4 to 145/HPF; mean, 49.7/HPF) with focal areas of sclerosis reminiscent of immunoglobulin G4-related lymphadenopathy, 4 (13%) cases resembled, in part, nodular sclerosis Hodgkin lymphoma, and 9 (29%) cases mimicked T-cell lymphoma. Among 33 patients with available clinical follow-up, 20 (61%) showed persistent or refractory disease despite antimycobacterial therapy, and 1 patient died of the disease. We conclude that the presence of ill-defined granulomas, clusters of neutrophils adjacent to the histiocytic aggregates, and some Epstein-Barr virus-positive cells are features highly suggestive of AOIS. A high index of clinical suspicion and awareness of the morphologic features and differential diagnosis of AOIS are helpful for establishing the diagnosis.

HIV Lymphadenopathy: Differential Diagnosis and Important Imaging Features.

OBJECTIVE. The purpose of this article is to review important imaging and clinical features to help elucidate causes of lymphadenopathy in patients with HIV infection. CONCLUSION. HIV lymphadenopathy has various causes generally categorized as inflammatory or reactive, such as immune reconstitution syndrome; infectious, such as tuberculous and nontuberculous mycobacterial infections and HIV infection itself; and neoplastic, such as lymphoma, Kaposi sarcoma, and Castleman disease. It is important to consider patients' demographic characteristics, clinical presentations, CD4 lymphocyte counts, and radiologic features to identify likely causes of lymphadenopathy.

Three Cases of Pediatric Multisystem Inflammatory Syndrome Associated with COVID-19 Due to SARS-CoV-2.

BACKGROUND Coronavirus disease 2019 (COVID-19) infection commonly presents as fever, cough, and shortness of breath in adults. Children are thought to have milder respiratory symptoms and to recover more quickly. We describe a new presentation of COVID-19 infection in children consisting of multisystem inflammation with decreased left ventricular function and evidence of lung disease. CASE REPORT Three children presented with fever, conjunctivitis, dry and cracked lips, rash, and/or cervical lymphadenopathy for at least 5 days. Two of these children required mechanical ventilation, and 1 of the 2 needed extracorporeal membrane oxygenation (ECMO) to support cardiorespiratory function. All of these children had moderate to severe hyponatremia and lymphopenia, which is usually seen in COVID-19. They were treated with intravenous immunoglobulin and high-dose aspirin. All of the children recovered. CONCLUSIONS Early recognition of children with multisystem inflammation is important because they are at increased risk for deterioration. Treatment with intravenous immunoglobulin and aspirin was used because this regimen has been shown to be beneficial in vasculitis of Kawasaki disease. The development of shock due to cardiac involvement may require ECMO.

CT imaging features of COVID-19 pneumonia: initial experience from Turkey.

PURPOSE: We aimed to demonstrate the computed tomography (CT) findings observed at the initial presentation of coronavirus disease 2019 (COVID-19) pneumonia and reveal the most frequent infiltration and distribution patterns of the disease. METHODS: One hundred and eighty-five patients (87 men, 98 women; mean age, 48.7 years), who underwent RT-PCR sampling and high-resolution CT examination in our hospital between March 15, 2020, and April 15, 2020, and got a definitive diagnosis of COVID-19 disease via initial or follow-up RT-PCR test, were included in the study. We comprehensively analyzed the most common and relatively rare CT imaging features (e.g., distribution pattern, density of the lesions, additional CT signs) in patients diagnosed with COVID-19 pneumonia. RESULTS: Thirty-eight patients (20.6%) had no evidence of pneumonia on their initial high-resolution CT images. Among 147 patients (79.4%) who had parenchymal infiltration consistent with pneumonia, 10 (6.8%) had a negative baseline RT-PCR test, and positivity was detected as a result of repeated tests. Most of the patients had multifocal (89.1%) and bilateral (86.4%) lesions. The most common location, right lower lobe, was affected in 87.8% of the patients. Lesions were distributed predominantly at peripheral (87.1%) and posterior (46.3%) areas of lung parenchyma. Most of the patients had pure ground glass opacity (GGO) (82.3%) followed by GGO with consolidation (32.7%) and crazy paving pattern (21.8%). Pure consolidation, solid nodules, halo sign, reverse halo sign, vascular enlargement, subpleural line, air-bronchogram, and bronchiectasis were the other findings observed in at least 15% of the cases. Halo sign, acinar nodules, air-bubble sign, pleural thickening and effusion, mediastinal and/or hilar lymphadenopathy were seen rarely (2%-12.9%). Pericardial effusion, pneumothorax, cavitation, and tree-in-bud pattern were not detected in our study group. CONCLUSION: Multifocal and bilateral GGO infiltration predominantly distributed in peripheral, posterior, and lower lung areas was the most common infiltration pattern.

Diagnostic performance of chest CT to differentiate COVID-19 pneumonia in non-high-epidemic area in Japan.

PURPOSE: To evaluate the diagnostic performance of chest CT to differentiate coronavirus disease 2019 (COVID-19) pneumonia in non-high-epidemic area in Japan. MATERIALS AND METHODS: This retrospective study included 21 patients clinically suspected COVID-19 pneumonia and underwent chest CT more than 3 days after the symptom onset: six patients confirmed COVID-19 pneumonia by real-time reverse-transcription polymerase chain reaction (RT-PCR) and 15 patients proved uninfected. Using a Likert scale and its receiver operating characteristic curve analysis, two radiologists (R1/R2) evaluated the diagnostic performance of the five CT criteria: (1) ground glass opacity (GGO)-predominant lesions, (2) GGO- and peripheral-predominant lesions, (3) bilateral GGO-predominant lesions; (4) bilateral GGO- and peripheral-predominant lesions, and (5) bilateral GGO- and peripheral-predominant lesions without nodules, airway abnormalities, pleural effusion, and mediastinal lymphadenopathy. RESULTS: All patients confirmed COVID-19 pneumonia had bilateral GGO- and peripheral-predominant lesions without airway abnormalities, mediastinal lymphadenopathy, and pleural effusion. The five CT criteria showed moderate to excellent diagnostic performance with area under the curves (AUCs) ranging 0.77-0.88 for R1 and 0.78-0.92 for R2. The criterion (e) showed the highest AUC. CONCLUSION: Chest CT would play a supplemental role to differentiate COVID-19 pneumonia from other respiratory diseases presenting with similar symptoms in a clinical setting.

The characteristics and clinical value of chest CT images of novel coronavirus pneumonia.

AIM: To investigate the characteristics and clinical value of chest computed tomography (CT) images of novel coronavirus pneumonia (NCP). MATERIALS AND METHODS: Clinical data and CT images of 80 cases of NCP were collected. The clinical manifestations and laboratory test results of the patients were analysed. The lesions in each lung segment of the patient's chest CT images were characterised. Lesions were scored according to length and diffusivity. RESULTS: The main clinical manifestations were fever, dry cough, fatigue, a little white sputum, or diarrhoea. A total of 1,702 scored lesions were found in the first chest CT images of 80 patients. The lesions were located mainly in the subpleural area of the lungs (92.4%). Most of the lesions were ground-glass opacity, and subsequent fusions could increase in range and spread mainly in the subpleural area. Pulmonary consolidation accounted for 44.1% of all of the lesions. Of the 80 cases, 76 patients (95%) had bilateral lung disease, four (5%) patients had unilateral lung disease, and eight (10%) patients had cord shadow. CONCLUSION: The chest CT of NCP patients is characterised by the onset of bilateral ground-glass lesions located in the subpleural area of the lung, and progressive lesions that result in consolidation with no migratory lesions. Pleural effusions and mediastinal lymphadenopathy are rare. As patients can have inflammatory changes in the lungs alongside a negative early nucleic acid test, chest CT, in combination with epidemiological and laboratory tests, is a useful examination to evaluate the disease and curative effect.

Analysis of the causes of cervical lymphadenopathy using fine-needle aspiration cytology combining cell block in Chinese patients with and without HIV infection.

BACKGROUND: Cervical lymphadenopathy refers to a frequently observed clinical presentation in numerous pathological conditions. A wide spectrum of diseases can cause cervical lymphadenopathy, irrespective of the fact that the patients are infected with HIV or not. The present study focuses on validating whether the causes of cervical lymphadenopathy differ significantly in HIV and non-HIV patients by using fine-needle aspiration cytology (FNAC) combining cell block. METHODS: A total of 589 patients with cervical lymphadenopathy were recruited in the FNA clinic. The samples were obtained by an auto-vacuumed syringe that benefited the sampling more materials. The cytological smears were prepared by Hematoxylin and Eosin (HE), Periodic Acid Schiff (PAS), Gomori's methenamine silver (GMS) and acid-fast staining. Cell blocks were made if required, and immunohistochemistry stain was performed on the cell block section. RESULTS: The study found 453 (76.9%) patients with HIV and 136 (23.1%) patients without HIV infection. The average age of HIV-infected patients was 34.8 ± 10.2 years, which was significantly lower than that of non-HIV-infected patients (42.9 ± 18.1 years) (p < 0.01). Of all patients infected with HIV, 390 (86.1%) were males. This proportion was significantly higher than that of non-HIV-infected patients [65/136 (47.8%)] (p < 0.01). The major causes of cervical lymphadenopathy in HIV positive patients were mycobacterial infection (38.4%), reactive hyperplasia (28.9%), non-specific inflammation (19.9%), and malignant lesions (4.2%). In contrast, the most common causes in HIV negative patients were reactive hyperplasia (37.5%), malignancy (20.6%), non-specific inflammation (19.1%) and mycobacterial infection (12.5%). Opportunistic infections such as non-tuberculous mycobacteria (4.2%), cryptococcosis (1.5%), Talaromyces marneffei (1.5%) and other fungi (0.4%) were found only in HIV-infected individuals. Non-Hodgkin's lymphoma (2.4%) was the most common malignant lesion in patients with HIV infection, followed by Kaposi's sarcoma (0.9%) and metastatic squamous cell carcinomas (0.7%). However, the most common malignancy in non-HIV-infected patients was metastatic carcinomas (14%) including small cell carcinomas, adenocarcinomas, squamous cell carcinomas and hepatocellular carcinoma, which were noticeably greater than the HIV patients (p < 0.01). CONCLUSIONS: There were significantly different causes of cervical lymphadenopathy in HIV infected and non-HIV infected patients. FNAC was a useful diagnostic method for differential diagnosis of cervical lymphadenopathy.

[Adult T cell lymphoblastic leukemia/lymphoma by HTLV-1 in a young woman]. / Leucemia/linfoma T del adulto tipo linfomatoso por HTLV-1 en una mujer joven.

Adult T cell lymphocyte leukemia/lymphoma (ATLL) is a subtype of T-cell lymphoma caused by infection of the human T-cell lymphotropic virus type 1 (HTLV-1); which generates a pro-viral integration into the host DNA, resulting in a clonal expansion of T lymphocytes. We present the case of a 20-year-old woman who developed multiple lymphadenopathies, hepatosplenomegaly and fever, serum positivity for HTLV-1 and proviral integration in the host DNA, demonstrated by polymerase chain reaction (PCR). Immunohistochemistry of lymphoid node was positive to CD4+ and CD8+ T cells. ATLL has been described in all HTLV-1 endemic areas, however, there are differences in the mean age of its presentation in such areas: 40 to 50 years in South America, 60 years in Japan. We showed one of few reported cases of the lymphoma type of ATLL in young adults.

High prevalence of pulmonary findings in computed tomographies of HTLV-1-infected patients with and without adult-T cell leukemia/lymphoma - implications for staging.

Lung involvement has been reported in HTLV-1 carriers and in patients with ATLL. Whether there are differences in the pattern of lung involvement between ATLL and HTLV carriers in North American patients is unknown. We aimed to compare CT pulmonary findings among patients with HTLV-1 infection with and without ATLL. Among 140 patients with HTLV-1 diagnosis, 97 had CT chest available. Of these, 72 (74.2%) had ATLL and 25 (25.8%) did not have ATLL. CT chest abnormalities were present in 90 (92.8%) participants (94.4% in ATLL; 88% in non-ATLL). Higher rates of lymphadenopathy (69.4% versus 24%, p < .01) and lower rates of bronchiectasis (25% versus 48%, p = .04) were seen in ATLL compared to non-ATLL. Our study supports that staging of lung involvement in ATLL should consider HTLV-associated pulmonary findings as not all CT chest abnormalities necessarily represent malignant infiltration.

An unusual case of Kaposi sarcoma masquerading as cystitis in a kidney transplant recipient.

Human Herpes Virus-8 (HHV-8) may reactivate in immunocompromised patients including recipients of solid organ transplants. Reactivation of HHV-8 may result in Kaposi sarcoma (KS). KS typically occurs with dermatologic involvement but can affect virtually any other organ; most commonly the gastrointestinal tract. We present a diagnostically challenging case of KS in a South American woman 7 months after kidney transplant. She presented with recurrent urinary tract infection manifested by pelvic pain and dysuria. Imaging studies revealed bladder thickening with pelvic lymphadenopathy. Findings on tissue biopsied from the bladder and lymph nodes were consistent with KS. Her skin was not affected. This case illustrates that KS and other HHV-8-related diseases should be on the differential diagnosis as a cause of mass lesions as well as lymphadenopathy in transplant recipients. The case exemplifies the need to pursue a tissue diagnosis in immunocompromised patients when a diagnosis is uncertain.

Kaposi Sarcoma Herpesvirus Inflammatory Cytokine Syndrome-like Clinical Presentation in Human Immunodeficiency Virus-infected Children in Malawi.

We describe 7 human immunodeficiency virus-infected Malawian children with Kaposi sarcoma who met criteria for Kaposi sarcoma herpesvirus (KSHV) inflammatory cytokine syndrome. Each presented with persistent fevers, bulky lymphadenopathy, massive hepatosplenomegaly, and severe cytopenias. Plasma analyses were performed in 2 patients, both demonstrating extreme elevations of KSHV viral load and interleukin 6.

Radiologic Extranodal Extension Portends Worse Outcome in cN+ TNM-8 Stage I Human Papillomavirus-Mediated Oropharyngeal Cancer.

PURPOSE: To identify adverse radiologic nodal features in cN+ TNM-8 stage I human papillomavirus-related (HPV+) oropharyngeal cancer (OPC). METHODS AND MATERIALS: All patients with HPV+ cT1-T2cN1 OPC treated with definitive intensity modulated radiation therapy from 2008 to 2015 were included. Radiologically involved lymph node number (LN), radiologic extranodal extension (rENE), retropharyngeal LN (RPLN), and lower neck (level 4 or 5b) LN involvement were assessed on pre-treatment computed tomography/magnetic resonance imaging by a specialized head and neck neuroradiologist. Disease-free survival (DFS), locoregional control, and distant control were compared between those with versus without rENE. Univariable and multivariable analysis with stepwise modal selection were applied to identify prognostic factors for DFS. RESULTS: A total of 45 rENE+ and 234 rENE- were identified. The rENE+ cohort had a higher number of LNs per patient (median: 6 vs 2, P < .001) and was more likely to have necrotic LNs (33 [73%] vs 132 [56%], P = .046). Median follow-up was 4.8 years. Although locoregional control was high in both cohorts (93% vs 97%, P = .34), the rENE+ group had inferior 5-year distant control (78% [59-88] vs 95% [91-97], P < .001) and DFS (58% [43-77] vs 90% [86-94], P < .001). In multivariable analysis, rENE+ (HR [hazard ratio] 4.3 [2.3-8.1], P < .001], T2 (vs T1) category (HR 2.1 [1.0-4.2], P = .039), smoking pack-years (HR 1.02 [1.0-1.03], P = .013), and the addition of systemic agents (HR 0.4 [0.2-0.8], P = .005) were prognostic for DFS. RPLN was prognostic for distant metastasis (HR 3.2, P = .013) but not for DFS after adjusting for rENE. CONCLUSIONS: Data from this contemporaneously treated cT1-T2N1 HPV+ OPC cohort suggest that the presence of rENE is an independent prognostic factor within stage I HPV+ OPC. RPLN is also associated with DM risk but not with DFS.

Leucemia/linfoma T del adulto tipo linfomatoso por HTLV-1 en una mujer joven / Adult T cell lymphoblastic leukemia/lymphoma by HTLV-1 in a young woman

Resumen La leucemia/linfoma T del adulto (LLTA) de tipo linfomatoso es un subtipo del linfoma de las células T, causado por la infección del virus linfotrópico de células T humanas tipo 1 (HTLV-1); el cual genera una integración proviral en el ADN del hospedero y expansión clonal de linfocitos T. Presentamos el caso de una mujer de 20 años que desarrolló linfadenopatías múltiples, hepatoesplenomegalia y fiebre, con serología positiva para HTLV-1 y reacción de polimerasa en cadena (RPC) con la integración proviral en el ADN del hospedero. La inmunohistoquímica en un ganglio linfático fue positiva para células T CD4+ y CD8+. La LLTA ha sido descrito en todas las áreas endémicas del HTLV-1; sin embargo, existen diferencias en la edad de presentación según la región: 40 a 50 años en América del Sur y 60 años en Japón. Presentamos uno de los pocos casos reportados de LLTA de tipo linfomatoso en adultos jóvenes.

Adult T cell lymphocyte leukemia/lymphoma (ATLL) is a subtype of T-cell lymphoma caused by infection of the human T-cell lymphotropic virus type 1 (HTLV-1); which generates a pro-viral integration into the host DNA, resulting in a clonal expansion of T lymphocytes. We present the case of a 20-year-old woman who developed multiple lymphadenopathies, hepatosplenomegaly and fever, serum positivity for HTLV-1 and proviral integration in the host DNA, demonstrated by polymerase chain reaction (PCR). Immunohistochemistry of lymphoid node was positive to CD4+ and CD8+ T cells. ATLL has been described in all HTLV-1 endemic areas, however, there are differences in the mean age of its presentation in such areas: 40 to 50 years in South America, 60 years in Japan. We showed one of few reported cases of the lymphoma type of ATLL in young adults.

The diagnostic and prognostic values of plasma Epstein-Barr virus DNA for residual cervical lymphadenopathy in nasopharyngeal carcinoma patients: a retrospective study.

BACKGROUND: Currently, the diagnosis and treatment of nasopharyngeal carcinoma (NPC) patients with residual cervical lymphadenopathy following radical radiotherapy with or without chemotherapy are challenging. We investigated the prognosis of NPC patients with residual cervical lymphadenopathy and assessed the diagnostic and prognostic values of Epstein-Barr virus (EBV) DNA in these patients. METHODS: This study included 82 NPC patients who were diagnosed with suspected residual cervical lymphadenopathy following completion of antitumor therapy. Their plasma EBV DNA levels were measured using quantitative polymerase chain reaction (qPCR) before the initiation of treatment and before neck dissection. Fine needle aspiration cytology (FNAC) was performed in 21 patients. All patients had undergone neck dissection and postoperative pathological examination to identify the nature of residual cervical lymphadenopathy. The overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS) were calculated using the Kaplan-Meier method and compared using the log-rank test. The Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). Multivariable analysis was used to estimate the effect of potential prognostic factors on survival. RESULTS: Following a median follow-up of 52.6 months, compared with patients with negative postoperative pathological findings for residual cervical lymphadenopathy, the patients with positive findings had a significantly lower 3-year PFS rate (49.9% vs. 83.3%, P = 0.008). Among NPC patients with residual cervical lymphadenopathy, the patients with preoperative plasma EBV DNA > 0 copy/mL had a lower 3-year PFS rate than did those with no detectable EBV DNA (43.7% vs. 61.1%, P = 0.031). In addition, combining FNAC with preoperative EBV DNA detection improved the diagnostic sensitivity. Multivariable analysis demonstrated that residual cervical lymphadenopathy with positive postoperative pathological result was an independent prognostic factor for PFS and that detectable preoperative plasma EBV DNA was an independent prognostic factor for OS. CONCLUSIONS: Using FNAC combined with preoperative EBV DNA detection improves the sensitivity in diagnosing NPC with residual cervical lymphadenopathy. Compared with patients with undetectable EBV DNA, patients with detectable preoperative plasma EBV DNA have worse prognosis and may require a more aggressive treatment strategy.