First report of Serotype-1 Marek’s disease virus (MDV-1) with oncogenic form in backyard turkeys in Turkey: a molecular analysis study

Background Marek’s disease (MD) is a lymphoproliferative disease caused by Gallid alphaherpesvirus 2 (GaHV-2, MDV-1), which primarily affects chickens. However, the virus is also able to induce tumors and polyneuritis in turkeys, albeit less frequently than in chickens. Results This is the first study in Turkey reporting the molecular characterization of a MDV-1 strain detected in a flock of backyard turkeys exhibiting visceral lymphoma. Here, MEQ, vIL-8, pp38 and 132-bp tandem repeat regions, which are frequently preferred in the pathotyping of MDV-1, were examined. It was determined that the MEQ gene of MDV-1/TR-21/turkey strain obtained in the present study encoded 339 amino acids (1020 nt) and had four proline-rich repeat regions (PPPP). Based on the nucleotide sequence of the MEQ gene of the MDV-1/TR-21/turkey strain, a phylogenetic tree was created using the MEGA-X software with the Maximum Likelihood Method (in 1000 replicates). Our strain was highly identical (> 99.8) to the Italian/Ck/625/16, Polish (Polen5) and some Turkish (Layer-GaHV-2-02-TR-2017, Tr/MDV-1/19) MDV-1 strains. Also, nt and aa sequences of the MEQ gene of our strain were 99.1 and 99.41% identical to another Turkish strain (MDV/Tur/2019) originated from chickens. Sequence analysis of pp38 and vIL-8 genes also supported the above finding. The identity ratios of nucleotide and amino acid sequences of vIL-8 and pp38 genes of MDV-1/TR-21/turkey strain were 99.64–100% and 99.79–100%, respectively, when compared with those of the Polish strain. According to 132-bp tandem repeat PCR results, the MDV-1/TR-21/turkey strain had five copies. Conclusions These results suggested that the MDV-1/TR-21/turkey strain obtained from backyard turkeys can be either very virulent or very virulent plus pathotype, though experimental inoculation is required for precise pathotyping.

Innovative therapeutic concepts of progressive multifocal leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) is an opportunistic viral disease of the brain—caused by human polyomavirus 2. It affects patients whose immune system is compromised by a corresponding underlying disease or by drugs. Patients with an underlying lymphoproliferative disease have the worst prognosis with a mortality rate of up to 90%. Several therapeutic strategies have been proposed but failed to show any benefit so far. Therefore, the primary therapeutic strategy aims to reconstitute the impaired immune system to generate an effective endogenous antiviral response. Recently, anti-PD-1 antibodies and application of allogeneic virus-specific T cells demonstrated promising effects on the outcome in individual PML patients. This article aims to provide a detailed overview of the literature with a focus on these two treatment approaches.

Paraneoplastic Filiform Hyperkeratosis and Immunoglobulin-Associated Vasculitis in Myeloma Progression: A Case Report

Multiple myeloma is a lymphoproliferative disease, which rarely presents with skin involvement or associated symptoms. Better awareness of these dermatological presentations is required for early diagnosis and to guide the patient towards appropriate therapy. We report on a patient with diffuse filiform hyperkeratosis and immunoglobulin-associated vasculitis in a severe progression of a known myeloma.

A rare disease with pregnancy: Castleman case report

Castleman’s disease was first described by Castleman et al. in 1956 as a non-lymphoproliferative disease. Castleman’s disease (CD), or angiofollicular lymphoid hyperplasia, is a rare disease with unknown etiology that can be easily misdiagnosed as lymphoma, neoplasm, or infection. Very few cases of pelvic origin and observed in pregnancy have been reported in the literature and are usually asymptomatic. Preoperative diagnosis is very difficult due to nonspecific imaging findings and rarity; most cases are diagnosed based on postoperative pathological examination. In this paper, a case of a 36-year-old pregnant woman suspected of adnexal origin in the uterine posterolateral, which was detected incidentally by ultrasound, was presented. The patient underwent a successful mass excision. Pathology of mass observed to be in the pelvic retroperitoneum was detected as localized unicentric and hyaline vascular CD. The study was conducted to discuss the diagnostic tools and perioperative management needed to identify the retroperitoneal unicentric Castleman case

Case Report: Meningoencephalitis With Thrombotic Occlusive Vasculopathy in a Young EBV-Naïve Boy Is Associated With a Novel SH2D1A Mutation

X-linked lymphoproliferative disease (XLP1) is a combined immunodeficiency characterized by severe immune dysregulation caused by mutations in the SH2D1A/SAP gene. Loss or dysfunction of SH2D1A is associated with the inability in clearing Epstein-Barr-Virus (EBV) infections. Clinical manifestation is diverse and ranges from life-threatening hemophagocytic lymphohistiocytosis (HLH) and fulminant infectious mononucleosis (FIM) to lymphoma and antibody deficiency. Rare manifestations include aplastic anemia, chronic gastritis and vasculitis. Herein, we describe the case of a previously healthy eight-year old boy diagnosed with XLP1 presenting with acute non-EBV acute meningoencephalitis with thrombotic occlusive vasculopathy. The patient developed multiple cerebral aneurysms leading to repeated intracerebral hemorrhage and severe cerebral damage. Immunological examination was initiated after development of a susceptibility to infections with recurrent bronchitis and one episode of severe pneumonia and showed antibody deficiency with pronounced IgG1-3-4 subclass deficiency. We could identify a novel hemizygous SH2D1A point mutation affecting the start codon. Basal levels of SAP protein seemed to be detectable in CD8+ and CD4+ T- and CD56+ NK-cells of the patient what indicated an incomplete absence of SAP. In conclusion, we could demonstrate a novel SH2D1A mutation leading to deficient SAP protein expression and a rare clinical phenotype of non-EBV associated acute meningoencephalitis with thrombotic occlusive vasculopathy.

CS-7 A case of Lymphomatoid granulomatosis with skin, lung, and intracranial lesions due to multicentric development

Introduction: LYG is very rare tumor and composed of large EB-positive B cells and reactive T cells. In this study, we experienced a case of LYG with multiple intracranial, cutaneous, and pulmonary masses. We report the pathogenesis and pathophysiology of LYG, including a discussion of the literature. case: A 69-year-old female presented with a growing lump in her lower back that had been present for several years. Six months later, she was found to have multiple masses in her lungs and intracranial region and underwent surgical removal for diagnostic purposes. Intraoperative findings: The tumor was substantial, reddish to grayish-white in color, and the margins of the tumor were whitish and hard, with some areas that could not be detached. Pathological findings: There were no atypical lymphocytes, and a small number of EBER-positive cells were observed. IgVH PCR: IgVH PCR was performed on the skin lesions and intracranial lesions, and bands of different sizes were detected, suggesting that the IgVH clone was present in the polyclonal region. Finally, we diagnosed LYG grade 1. discussion: EB-associated lymphoproliferative disease can lead to polyclonal reactive growth or monoclonal neoplastic growth depending on the balance between morphology and host immunity. The results of IgVH PCR suggest that the skin lesions did not cause multiple metastases, but rather that the enlargement of the skin lesions triggered intracranial and pulmonary lesions in an allo-centric manner. The results of IgVH PCR suggested that the skin lesions did not cause multiple metastases, but rather that the skin lesions grew to cause intracranial and pulmonary involvement in an other-centric manner.

Occurrence of Marek's disease in vaccinated Algerian broiler breeder flocks: A histopathological survey

Background and Aim: Marek's disease (MD) is a lymphoproliferative disease that occurs in chickens. In the absence of control measures, MD causes devastating losses to commercial poultry flocks. Vaccination has enabled dramatic success in the prevention and control of MD. However, the MD vaccination program has failed frequently, and occasional clinical outbreaks have been reported in the vaccinated flocks as well. The present study aimed to describe the clinical and histopathological characteristics of the field cases of MD in broiler breeder flocks. Materials and Methods: A survey on the update of MD occurrence in Algerian broiler breeder flocks was conducted from June 2020 to September 2020. Ten vaccinated broiler breeder flocks located in Central Algeria and having progressive tumors in different visceral organs were evaluated for MD virus infection by conducting a histopathological examination of the birds. Results: The age of the birds affected with MD ranged from 13 to 22 weeks. The mortality rate varied sensitively from 4% to 10%. The clinical symptoms reported in the affected flocks included locomotor, nervous, digestive, and respiratory symptoms. Necropsy of the dead or euthanized birds revealed visceral lymphomatosis in several organs and macroscopic changes in the peripheral nerves (including loss of longitudinal striation, color change [grayish], and volume increase). The histopathological findings included the infiltration and proliferation of lymphocytes and blast cells (lymphoblasts) in various organs of the birds, which are the typical characteristics of MD and, therefore, confirmed the field infection of MD in these birds. Conclusion: The present study provided evidence for the high prevalence of MD in the broiler breeder flocks vaccinated with a bivalent vaccine (turkey herpesvirus+Rispens) at the hatchery. The findings of the present study may indicate highlevel failure of vaccination in these birds.

The phenomenon of pseudoprogression in cancer immunotherapy: is everything so unambiguous?

When evaluating the effect of therapy for malignant neoplasms with inhibitors of CTLA-4, PD-1 and PD-L1, the phenomenon of pseudoprogression may occur. Pseudoprogression is an increase in the volume of tumor tissue due to immunocompetent cells (lymphocytes, macrophages) mobilized into the tumor focus under the action of immunotherapy. As the antitumor effect of lymphocytes and macrophages is realized, the tumor decreases or disappears over time. Pseudoprogression occurs with varying frequency in various types of cancer. It may also matter which immune checkpoint inhibitors is used to treat a solid tumor or lymphoproliferative disease. Currently, several immune-related response-evaluation criteria have been developed, which can help diagnose the phenomenon of pseudoprogression. But, unfortunately, none of these criteria clearly distinguish pseudoprogression from true tumor progression. In the case of an erroneous judgment about the effect of treatment, immunotherapy ends, and the patient may not get a chance for long-term remission. Using two clinical examples (immunotherapy for metastatic kidney cancer and recurrent Hodgkin lymphoma), the authors discuss the pitfalls of evaluating the effectiveness of treatment with checkpoint inhibitors.

Subaxial cervical Castleman’s disease: A rare cause of myelopathy

Background: Castleman’s disease (CD) is a rare lymphoproliferative disease of unknown origin which rarely affects the spine. Here, we present CD involving a lytic, destructive C3 lesion with extension into the spinal canal contributing to upper cervical cord compression. Notably, the lesion mimicked other primary bone lesions, metastatic tumors, and/or lymphoma. Case Description: A 52-year-old male presented with progressive quadriparesis (i.e. weakness, instability of gait) and loss of dexterity in both hands over 2 weeks. The MRI, X-ray, and CT scans revealed a destructive lytic lesion involving the C3 vertebral body (i.e. including both anterior and posterior elements). The patient underwent a C3 total and C4 partial laminectomy followed by a C2-C4/5 instrumented fusion (i.e. included C2 pedicle screws/laminar screws, and C4/C5 lateral mass fixation). Histopathology showed a lymphoproliferative disorder with follicles of different sizes, central abnormal germinal structures, and a Mantle zone (i.e. expanded germinal centre with concentric layering with an “onionskin” appearance). These findings were all consistent with the diagnosis of CD (i.e. hyaline-vascular type). Conclusion: CD, a rare lymphoproliferative disease of unknown origin rarely affects the spine. Here, we presented a 52-year-old male with a C3 lytic lesion resulting in C3/4 cord compression that favorably responded to a C3/4 laminectomy with posterior instrumented fusion.