Primary effusion lymphoma occurring in the setting of transplanted patients: a systematic review of a rare, life-threatening post-transplantation occurrence.

BACKGROUND: Primary effusion lymphoma is a rare, aggressive large B-cell lymphoma strictly linked to infection by Human Herpes virus 8/Kaposi sarcoma-associated herpes virus. In its classic form, it is characterized by body cavities neoplastic effusions without detectable tumor masses. It often occurs in immunocompromised patients, such as HIV-positive individuals. Primary effusion lymphoma may affect HIV-negative elderly patients from Human Herpes virus 8 endemic regions. So far, rare cases have been reported in transplanted patients. The purpose of our systematic review is to improve our understanding of this type of aggressive lymphoma in the setting of transplantation, focusing on epidemiology, clinical presentation, pathological features, differential diagnosis, treatment and outcome. The role of assessing the viral serological status in donors and recipients is also discussed. METHODS: We performed a systematic review adhering to the PRISMA guidelines. The literature search was conducted on PubMed/MEDLINE, Web of Science, Scopus, EMBASE and Cochrane Library, using the search terms "primary effusion lymphoma" and "post-transplant". RESULTS: Our search identified 13 cases of post-transplant primary effusion lymphoma, predominantly in solid organ transplant recipients (6 kidney, 3 heart, 2 liver and 1 intestine), with only one case after allogenic bone marrow transplantation. Long-term immunosuppression is important in post-transplant primary effusion lymphoma commonly developing several years after transplantation. Kaposi Sarcoma occurred in association with lymphoma in 4 cases of solid organ recipients. The lymphoma showed the classical presentation with body cavity effusions in absence of tumor masses in 10 cases; 2 cases presented as solid masses, lacking effusions and one case as effusions associated with multiple organ involvement. Primary effusion lymphoma occurring in the setting of transplantation was more often Epstein Barr-virus negative. The prognosis was poor. In addition to chemotherapy, reduction of immunosuppressive treatment, was generally attempted. CONCLUSIONS: Primary effusion lymphoma is a rare, but often fatal post-transplant complication. Its rarity and the difficulty in achieving the diagnosis may lead to miss this complication. Clinicians should suspect primary effusion lymphoma in transplanted patients, presenting generally with unexplained body cavity effusions, although rare cases with solid masses are described.

Case Report: A Rare Case of Crimean-Congo Hemorrhagic Fever Associated with Epididymo-Orchitis.

Crimean-Congo hemorrhagic fever (CCHF) is an acute infectious disease that affects multiple organ systems and is characterized by extensive ecchymosis, internal hemorrhage, and hepatic dysfunction. The reported case fatality rate varies between 8% and 80%. It is frequently transmitted by Hyalomma ticks, which are endemic in the Northeast Anatolia region of Turkey in spring and summer. Our patient presented from an endemic area with fever, malaise, joint pain, and scrotal pain following a tick bite, and real-time PCR analysis of venous blood was positive for CCHF. Based on Doppler ultrasound performed because of the patient's scrotal pain, he was diagnosed as having epididymo-orchitis, which was considered secondary to CCHF after ruling out other etiologies and resolved with scrotal elevation and anti-inflammatory treatment. Being a very rare complication, this report aimed to document this case of CCHF-associated epididymo-orchitis in the literature.

Patent landscape of novel technologies for combating category-A Arenavirus infections.

INTRODUCTION: Arenavirus are unique category-A pathogens that are also classified as Orphan diseases. Very few options exist currently for treating Viral Hemorrhagic Fever (VHF) caused by viruses belonging to the Arenaviridae family [1]. The current review provides detailed patent landscape and a description of selected technologies developed for combating category-A Arenavirus. Currently, Arenavirus infections are epidemic [2] but could cause widespread pandemics due to ease of dissemination and lack of immunity against these viruses. AREAS COVERED: The key strings for selected Arenavirus VHF were run separately in MCPaIRS®, PatSeer, and Questel database. The search was limited to Title, Abstract and Claim fields; one member per patent family was considered for analysis. EXPERT OPINION: Synthetic molecules dominate the patent landscape, while natural products have not been extensively claimed for the treatment of Arenavirus infection. The broad-spectrum activity has been highly desired for Arenavirus treatment, but few reports have experimentally tested it. With each year, a constant increase in number of patents published is seen, while the maximum number of applications was filed in 2017. The research in VHF is driven by public funds; the maximum numbers of patents were filed by publicly funded organizations.

Human papillomavirus genotypes and P16INK4A expression in squamous penile carcinoma in Mexican patients.

BACKGROUND: Approximately 50% of cases of penile carcinoma (PeCa), a rare neoplasm worldwide, are associated with human papillomavirus (HPV). However, the detection of HPV-DNA is not sufficient to consider it the etiological factor in the development of this type of cancer. Currently, the overexpression of P16INK4A is used as a surrogate biomarker of HPV carcinogenesis. Information on PeCa in Mexico is scarce, particularly regarding cases related to HPV and genotype frequency. OBJECTIVE: To evaluate the presence of HPV, its genotypes, and the presence of multiple genotypes, and the expression of P16INK4A, as well as its clinical and histopathological parameters. METHODS: For HPV-DNA detection and P16INK4A expression, we used the INNO-LiPA® test and immunohistochemistry, respectively. RESULTS: Sixty cases of PeCa were evaluated, of which 75% were HPV-non-related histological variants. We found that 58.9% (33/56) of PeCa cases were HPV-DNA positive, while 30.9% of the cases evaluated (17/55) were positive for P16INK4A. HPV16 was the main genotype in 42.9% of the cases, followed by HPV52 in 7.1% and HPV18 in 5.4%. Within the HPV-positive cases, 27.3% had multiple genotypes. All HPV-positive patients under the age of 45 years were positive only for HPV16. CONCLUSIONS: HPV16 was the most commonly detected genotype in PeCa. HPV 31, 35 and 39 were infrequent; however, they were related to a single infection and P16INK4A overexpression; thus, they seem to be relevant in PeCa carcinogenesis. Our results suggest that P16INK4A overexpression could be useful for the classification of HPV-related PeCa. The role of multiple HPV genotypes in the development and prognosis of PeCa is still not completely understood. Thus, it is necessary to define criteria to establish reliable ways to classify HPV-related PeCa that could lead to optimal therapeutic approaches.

Effect of mobile phone text messaging for improving the uptake of influenza vaccination in patients with rare diseases.

OBJECTIVES: Influenza vaccine is recommended in some chronic medical conditions, including several rare diseases. The objectives of the study were to assess the effect of text message reminders on influenza vaccination uptake of patients with selected rare diseases and delayed vaccination, and to describe their characteristics. METHODS: Quasi-experimental pre-post intervention study performed along the 2016 influenza vaccination campaign in the Autonomous Community of Madrid. Unvaccinated patients diagnosed with a selected rare disease were targeted for intervention. SMS were sent to them at least one month after the beginning of the campaign, in four consecutive weeks. Those with no mobile phones available or no certainty of message reception, were assigned as controls. The association between the reception of the SMS and vaccination uptake was assessed using multiple poisson regression models. RESULTS: Of 69.040 patients with delayed vaccination, 87.2% received an SMS reminder in the asigned contact mobile telephone. Global influenza vaccine coverage reached 41.3%. The uptake of influenza vaccine was significantly higher among those receiving the reminder (9.3% vs. 7.1% in the control group, p < 0.001). Those who received a SMS reminder were 30% more likely to uptake seasonal influenza vaccine. By sex and age, the reception of the reminder was associated with a significantly higher probability of vaccination in men ≥65 years with at least a concurrent chronic condition (IRR: 1.58, CI95%: 1.25-2.00). Among women, this higher probability was detected in those between 14 and 64 years of age (IRR: 1.41, CI95%: 1.22-1.63), and ≥65 years without concurrent chronic conditions (IRR: 1.40, CI95%: 1.05-1.89). CONCLUSION: Although the intervention was modestly effective, it proved beneficial in some cases. It can be an additional strategy to improve vaccine uptake, since it is simple, feasible, affordable and easily scalable, particularly when immunization and target population data are available in population registries.

Severe fever and thrombocytopenia syndrome virus infection: Considerations for vaccine evaluation of a rare disease.

Infection caused by the severe fever and thrombocytopenia syndrome virus (SFTSV) causes a hemorrhagic illness with a mortality between 20% and 40%. Initially recognized in 2009 in China, cases have additionally been documented in Japan and Korea although retrospective studies have documented seroprevalence since 1996. Although case rates have increased due to increased awareness and more widely available diagnostics, SFTSV infection remains rare with the highest rates documented in Korea for Jeju Province (3.5 cases per 100,000 population) and the Inje-gun region (66.2 cases per 100,000). Because of the very low incidence of infection, a placebo-controlled study with 1:1 randomization to evaluate an SFTSV vaccine would require a sample size that is 25% greater than the region of study. We discuss alternatives to licensure. Vaccine effectiveness may be assessed through a registry, comparing rates of infection over time between vaccine recipients versus regional populations. Modeled data can be updated based on actual case rates and population changes over the years of follow-up. Using one model, statistically significant differences are seen after 10 years in Inje-gun and 15 years of follow-up in Jeju. This approach may be applicable to other uncommon infectious diseases for which a standard study design is difficult.

Cytopathologic characteristics of HPV-related small cell carcinoma of the oropharynx.

BACKGROUND: Human papillomavirus (HPV)-related squamous cell carcinoma (SqCC) of the oropharynx is an epidemiologically and clinically distinct form of SqCC that is associated with an improved prognosis. However, HPV-related small cell carcinoma of the oropharynx is a rare and newly described variant that is associated with aggressive clinical behavior and poor outcomes. To date, fewer than 2 dozen reports of this entity exist in the literature, and there is no discussion of cytopathologic features. This article reports 6 cases and discusses the salient cytomorphologic findings, ancillary studies, and challenges when this entity is encountered. METHODS: Anatomic pathology archives were searched to identify patients with a diagnosis of HPV-related small cell carcinoma of the oropharynx. Medical records were reviewed to document the following: age, sex, smoking status, other relevant clinical history, primary location, treatment, and clinical outcome. Both p16 and high-risk HPV in situ hybridization (ISH) studies were positive in at least 1 specimen from each patient. The pathologic diagnoses, cytomorphologic characteristics, immunocytochemical stains, and HPV ISH studies were reviewed and recorded for all available cases. RESULTS: Six patients with 11 cytopathology specimens of HPV-related small cell carcinoma of the oropharynx were identified. The mean age was 61.3 years, and all patients died with widely metastatic disease (mean, 23 months; range, 12-48 months). Mixed small cell carcinoma and SqCC components were present in half of the cases. CONCLUSIONS: The identification of a small cell component can be reliably performed with cytology preparations and is crucial because this (and not the HPV status) determines the prognosis.

Histopathological and immunohistochemical features of nodular podoconiosis.

BACKGROUND: Podoconiosis is a familial geochemical dermatosis which is common in Ethiopia but relatively unknown in Europe/United States. It is related to exposure of bare feet to volcanic soil and presents with extensive bilateral lymphedema of legs and feet. Histopathological and immunohistochemical features of it have not been described yet. OBJECTIVES: The objectives of this study are to characterize podoconiosis histopathologically and immunohistochemically and to increase awareness of the disease. METHODS: Ten specimens of fully developed podoconiosis were examined with hematoxylin/eosin, periodic acid-Schiff, Gram, elastica-van Gieson stainings, with immunohistochemistry (CD3,CD20,CD31,CD68,CD138, tryptase, podoplanin, collagen IV), and with polymerase chain reaction (PCR) for human papillomavirus (HPV)-specific DNA. RESULTS: All specimens showed verrucous acanthosis and papillomatosis. Eccrine ducts demonstrated hyperplasia, syringofibroadenomatous changes and miliaria. Dermal collagen bundles were thickened, and elastic fibers were dramatically reduced. A moderate lymphoplasmacytic infiltrate was joined by mast cells and scattered macrophages; neutrophils and eosinophils were sparse. Blood vessels were increased, dilated, and often sclerotic while lymphatics were reduced and largely not dilated. HPV-PCR was negative in all specimens. CONCLUSIONS: Podoconiosis demonstrates distinctive changes of chronic lymphedema with extensive sclerosis, loss of elastic fibers, verrucous acanthosis (not HPV induced) and reactive changes of eccrine structures. Mast cells, macrophages and altered blood vessels may be involved in the pathogenesis.

Merkel cell carcinoma: The first human cancer shown to be associated with a polyomavirus.

Merkel cell carcinoma (MCC) is a rare, malignant primary neuroendocrine cancer of the skin, usually affecting elderly, white people in sun-exposed areas. This is a highly aggressive tumor with strong propensity to metastasize. Surgery and radiation therapy remain the mainstay of treatment, with no curative treatment in case of disseminated metastases. Until 2008, MCC was thought to be caused by the malignant transformation of resident Merkel cells, but no investigation of a predominant molecular pathway that could be involved in MCC pathogenesis was successful. A real revolution in MCC understanding and management occurred in 2008, when a new human polyomavirus (MCPyV) was found to be the main etiological agent of this skin cancer. Following the discovery of MCPyV, the association of MCPyV with MCC has been confirmed worldwide, with detection of MCPyV in about 80% of MCCs. At the same time it had been shown that MCPyV infection is almost ubiquitous in healthy subjects, and MCPyV is thought to be persistent resident of the skin microbiome although the route of transmission, the host cell, the viral cycle and/or latency remain unknown. Most studies suggest that there may be two subtypes of MCC: MCPyV-positive (80%) and MCPyV-negative (20%) MCCs, and various studies have reported a better prognosis associated with MCPyV infection. The discovery of MCPyV in MCC patients opens up new therapeutic insights. The necessity and persistence of expression of MCPyV oncoproteins during MCC development make these proteins promising therapeutic targets.

Cytomegalovirus retinitis: a rare but preventable cause of blindness in dermatology patients.

IMPORTANCE: Dermatologists are using an increasing range of immunomodulatory therapies to treat an expanding number of skin diseases. Complications of therapy are broad and include infection. Cytomegalovirus (CMV) retinitis has not been reported in association with dermatologic disease. OBSERVATIONS: We report two cases of CMV retinitis associated with immunosuppression for eczema and pemphigus vulgaris. In both cases, patients were receiving corticosteroid and a second-line immunosuppressive agent (cyclosporine or mycophenolate mofetil). Disease presented in both patients with painless visual loss. CONCLUSIONS AND RELEVANCE: Patients receiving immunosuppressive therapy should be monitored for blurred vision, floaters, or visual loss and referred for urgent assessment to ensure accurate diagnosis and prompt treatment of possible CMV retinitis.

Bowen disease of the palm associated with human papillomavirus 52.

Human papillomavirus (HPV) is a well-known risk factor for many human cancers, especially cervical cancers. Among the nonmelanoma skin cancers, Bowen disease (BD) of the genitalia and fingers has also been shown to be closely associated with the high-risk types of HPV, especially HPV16. We report a case of BD of the palm, which is a very rare location for BD. In addition to its rare location, HPV52, which is classified as a mucous high-risk HPV type, was detected in the lesion by PCR restriction fragment length polymorphism analysis. To our knowledge, this is the first reported case of BD associated with HPV52.

[Study of prevalence of rare and difficult to cultivate causative agents of inflammatory diseases of respiratory organs].

AIM: Study the prevalence of Mycoplasma pneumoniae, Chlamydophila pneumoniae, Chlamydophila psittaci, Legionella pneumophila, Moraxella catarrhalis, Cytomegalovirus, Herpes simplex I/II virus (HSV I/II) in individuals of various age groups with varying inflammatory broncho-pulmonary diseases. MATERIALS AND METHODS: 384 adults and 1001 children with clinically confirmed diagnoses were examined by PCR method: community-acquired pneumonia, acute bronchitis, bronchial asthma, ARD/ARVD, as well as 127 healthy children and 52 healthy adults. Sputum, smears from posterior fornix of pharynx, blood, saliva from children of the first year of life were used as material for the study. RESULTS: Wide prevalence of M. pneumoniae and C. pneumoniae among adults and M. pneumoniae among children older than 1 year with inflammatory diseases of respiratory organs was established. C. psittaci, L. pneumophila, M. catarrhalis occurred in isolated cases in both adults and children. Active replication of herpes group viruses was detected in patients of all age groups with inflammatory broncho-pulmonary diseases, and in children Cytomegalovirus replication predominated, in adults--HSV I/II. CONCLUSION: High frequency of prevalence of M. pneumoniae and C. pneumoniae in inflammatory diseases of respiratory tract was established, giving evidence of reasonability and necessity of examination of patients with various nosologic forms of diseases for these species of microorganisms with the aim of effective etiotropic therapy.

Primary nodal marginal zone B-cell lymphoma: clinical features and prognostic assessment of a rare disease.

This study defined the clinical features and assessed the prognosis of 47 patients (17 males, 30 females, median age 63 years) with primary nodal marginal zone B-cell lymphoma. Forty-five per cent had stage IV disease. Hepatitis C virus serology was positive in 24%. According to the Follicular Lymphoma International Prognostic Index (FLIPI), 33% were classified as low-risk, 34% as intermediate-risk, and 33% as high-risk. The 5-year overall survival (OS) was 69%. In univariate analysis worse OS was associated with: FLIPI (P = 0.02), age > 60 years (P = 0.05) and raised lactate dehydrogenase (P = 0.05). In multivariate analysis, only FLIPI predicted a worse OS (P = 0.02).

Thymic lymphoepitheliomalike carcinoma in children: clinicopathologic features and molecular analysis.

Thymic lymphoepitheliomalike carcinoma (LELC) in children is extremely rare and we report 2 such cases with molecular analysis of Epstein-Barr virus (EBV) and its encoded latent membrane protein-1 as well as a literature review. Both of our patients were male, presented with a huge anterior mediastinal mass, expired within a year after diagnosis despite treatment. There were altogether 9 cases of thymic LELC in children. Their common clinical features include a male predominance, large tumor size, advanced clinical stage, and poor clinical outcome. All cases were associated with EBV and nearly half developed concurrent hypertrophic osteoarthropathy (HOA). Thymic LELC in children is an aggressive EBV-associated malignant tumor frequently accompanied by HOA. We proposed that EBV might play a role in the development of HOA through the interactions of latent membrane protein-1, vascular endothelial growth factor, and cyclooxygenases-2.

An unusual form of Riedel's thyroiditis: a case report and review of the literature.

We report the case of a 36-year old woman with a history of long-term fever associated with a biologic inflammatory syndrome that was not corrected by several courses of corticosteroid treatment. The only remarkable result during previous investigations was the presence of a positive Epstein-Barr virus (EBV) serology. Clinical examination revealed an heterogenous thyroid with a nodule on the right lobe. Serum thyrotropin (TSH) concentration was normal. The levels of antiperoxidase antibodies and thyrocalcitonin were normal. Ultrasound examination of the neck showed a 3-cm hypoechogenous nodule in the right lobe of the thyroid. A total thyroidectomy was performed. Histopathologic findings led to the diagnosis of Riedel's thyroiditis. We observed a dramatic improvement after surgery with absence of fever and normalization of inflammatory parameters. The role of EBV infection in the process of this unusual form of Riedel's thyroiditis is discussed.