Contiguous squamous proliferations in syringocystadenoma papilliferum: A retrospective study of 14 cases

Background: Syringocystadenoma papilliferum is a benign adnexal neoplasm. Contiguous squamous proliferation has been rarely described in syringocystadenoma papilliferum. Aims: This study aimed to evaluate the spectrum and pathogenesis of contiguous squamous proliferation in syringocystadenoma papilliferum. Materials and Methods: All cases of syringocystadenoma papilliferum diagnosed over the past 12 years were screened for contiguous squamous proliferation. Cases with associated nevus sebaceous were excluded from the study. Immunohistochemistry for GATA3, CK7, BRAFV600E and p16 was performed. PCR for human papilloma virus, type 16 and 18, was carried out. Results: Of a total of 30 cases, 14 cases showed associated contiguous squamous proliferation which included four cases of verrucous hyperplasia, six cases with papillomatosis, two cases with mild squamous hyperplasia and one case each of Bowen’s disease and squamous cell carcinoma. In the cases with non-neoplastic contiguous squamous proliferations, the squamous component did not express CK7 or GATA3. However, the squamous component of premalignant and malignant lesions expressed CK7 and GATA3 concordant with the adenomatous component. BRAF was positive in adenomatous component in five cases while the contiguous squamous proliferation component was negative for BRAF in all but one case. p16 was negative in both components of all cases and PCR for human papilloma virus was negative in all cases. Limitations: Due to the rarity of disease, the sample size of our study was relatively small with two cases in the 2nd group, that is, syringocystadenoma papilliferum with malignant contiguous squamous proliferation. Detailed molecular studies such as gene sequencing were not performed. Conclusion: Syringocystadenoma papilliferum with contiguous squamous proliferation is underreported, and most commonly displays verrucous hyperplasia. The premalignant and malignant contiguous squamous proliferations likely arise from syringocystadenoma papilliferum while the hyperplastic contiguous squamous proliferations likely arise from the adjacent epidermis. Relationship with high-risk human papilloma virus is unlikely. However, further molecular analysis of larger number of cases is required to establish the pathogenesis.

Computational modeling of virucidal inhibition mechanism for broad-spectrum antiviral nanoparticles and HPV16 capsid segments

Solid core nanoparticles coated with sulfonated ligands that mimic heparan sulfate proteoglycans (HSPG) can exhibit virucidal activity against many viruses that utilize HSPG interactions with host cells for the initial stages of the infection. How the interactions of these nanoparticles with large capsid segments of HSPG-interacting viruses lead to their virucidal activity has been unclear. Here, we describe the interactions between sulfonated nanoparticles and segments of the human papilloma virus type 16 (HPV16) capsids using atomistic molecular dynamics simulations. The simulations demonstrate that nanoparticles primarily bind at interfaces of two HPV16 capsid proteins. Insertions of nanoparticles at these interfaces leads to increased separation in distances and angles between capsid proteins. As the time progresses, the nanoparticle binding can lead to breaking of contacts between two neighboring proteins. The revealed mechanism of nanoparticles targeting the interfaces between pairs of capsid proteins can be utilized for designing new generations of virucidal materials and contribute to the development of new broad-spectrum non-toxic virucidal materials.Abstract Figure

IMMUNOHISTOCHEMICAL FEATURES OF THE EXPRESSION OF HUMAN PAPILLOMA VIRUS TYPE 16 IN PLEOMORPHIC ADENOMAS OF SALIVARY GLAND

The aim is to reveal the immunohistochemical features of human papilloma virus type 16 expression in various histological variants of pleomorphic adenomas of the salivary gland. Materials and methods: The material of the study was surgical and biopsy material from 30 patients with pleomorphic adenomas of the salivary glands, among which in 15 cases mesenchymal was detected, in 10 – mixed, in 5 cases – epithelial histological variant, respectively. Immunohistochemical study was performed, using mouse monoclonal antibody to human papilloma virus type 16. Visualization was performed, using an EnVisionTM FLEX detection system. Histological sections of grade III cervical intraepithelial neoplasia (CIN III) were used as a positive control; for a negative control, the procedure was performed without primary antibodies. The immunohistochemical reaction was assessed by a semi-quantitative method by counting the percentage of positively stained cells in the field of view of a microscope × 400. Microspecimens were studied, photoarchived on an Olympus BX-41 microscope. Results: Expression of human papilloma virus type 16 of varying severity was determined in 26 cases of pleomorphic adenomas of the salivary glands, which was 86.7%. The epithelial component of the pleomorphic adenoma of the salivary gland was characterized by a more pronounced expression of the monoclonal antibody to human papilloma virus type 16 compared to the mesenchymal component of the tumor. The severity of the immunohistochemical reaction with a monoclonal antibody to human papilloma virus type 16 depended on the histological variant of the pleomorphic adenoma of the salivary gland. Epithelial, mixed and mesenchymal variants of pleomorphic adenoma of the salivary gland were characterized, respectively, by the most pronounced, pronounced and moderately pronounced expression of a monoclonal antibody to human papilloma virus type 16. Conclusions: A comprehensive immunohistochemical study with a monoclonal antibody to human papilloma virus type 16 revealed the presence of a causal relationship between the infection of a patient with human papilloma virus type 16 and development of pleomorphic adenoma of the salivary gland in him.

EXPRESSION FEATURES OF HUMAN PAPILLOMA VIRUS TYPE 16 AND ANTI-EPSTEIN-BARR VIRUS IN PLEOMORPHIC ADENOMA, SURROUNDING AND INTACT SALIVARY GLAND

The aim is to reveal the expression features of MCA to human papilloma virus type 16 and anti-Epstein-Barr virus in the pleomorphic adenoma, surrounding and intact salivary gland. Materials and methods: It was used surgical and biopsy material from 30 patients, represented by pleomorphic adenomas with surrounding to tumor tissue of the salivary gland and intact tissue of the salivary gland (the distance between the tumor and the intact salivary gland – 10 mm). Immunohistochemical study was performed using mouse monoclonal antibody (MCA) to human papilloma virus type 16 (clone CAMVIR-1, «Diagnostic BioSystems», USA) and anti-Epstein-Barr virus (LMP, clone CS. 1-4, «Dako», Denmark). Visualization was performed, using an EnVisionTM FLEX detection system (Dako, Denmark). Antigen unmasking was carried out in citrate buffer pH 6.0 at 95°C. Primary antibodies were incubated at room temperature for 30 minutes, secondary antibodies – 20 minutes. Sections were counterstained with Gill hematoxylin. We assessed the immunohistochemical reaction by a semi-quantitative method by counting the percentage of positively stained cells in the field of view of a microscope × 400. Microspecimens were studied and photoarchived on an Olympus BX-41 microscope (Japan). Results: In this study it was detected a positive immunohistochemical reaction with MCA to human papilloma virus type 16 and anti-Epstein-Barr virus, respectively, in 26 (86.7%) and 8 (26.7%) cases. Epithelial, mixed and mesenchymal variants of pleomorphic adenoma of the salivary glands are characterized, respectively, by the severely expressed, moderately expressed and minimally expressed of MCA to human papilloma virus type 16 and anti-Epstein-Barr virus. The parenchymal component of pleomorphic adenoma is characterized by more marked expression of these markers as compared to the stromal component. The epithelial cells of the salivary glands, surrounding the pleomorphic adenoma, as well as intact salivary glands, express MCA to human papilloma virus type 16 and anti-Epstein-Barr virus. The severity of the expression of these markers in the salivary gland is determined by the histological variant of the tumor (severely expressed in the epithelial variant, moderately expressed in the mixed variant, and minimally expressed in the mesenchymal variant). Conclusions: The immunohistochemical study has shown that the Epstein-Barr virus and, especially, human papilloma virus type 16 can act as exogenous trigger factors involved in the development of pleomorphic adenoma of the salivary glands. The revealed immunohistochemical features of MCA expression to human papilloma virus type 16 and anti-Epstein-Barr virus in the salivary gland surrounding the pleomorphic adenoma and in the intact tissue of the salivary gland make it possible to recommend the extracapsulardissection of the tumor with resection of the adjacent intact tissue of the salivary gland at a distance of 10 mm in patients with pleomorphic adenoma.

Highly proliferative anal neuroendocrine carcinoma: molecular and clinical features of a rare, recurrent case in complete remission

Background Poorly differentiated anal neuroendocrine carcinomas (ANECs) are rare lesions with poor prognosis, and the molecular etiology is only partially understood. Case presentation At our institution, we have treated and followed a patient with such a rare ANEC. He had primarily surgery followed by three rounds of repeated surgery for loco-regional recurrences. He also received three different combinations of chemotherapy and external beam radiation. At last follow-up 13 years since the primary diagnosis, the patient had been in complete remission for nine years. The patient’s medical files were re-examined, including laboratory, radiology and clinical examinations. Histopathology was re-assessed, and expanded immunohistochemistry was performed from tissue specimens from the four surgical procedures. In addition, the molecular genetic status was evaluated through next-generation sequencing. The initial tumor was consistent with a 59 mm small cell neuroendocrine cancer with a Ki-67 index of 80%. Regional lymph node metastases were evident, and immunohistochemistry supported a neuroendocrine origin. A PCR screening detected human papilloma virus type 45 DNA (high-risk subtype), and focused next-generation sequencing found a missense mutation in the Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha (PIK3CA) gene. In tissues representing subsequent recurrences, the Chromogranin A expression was lost, and the Ki-67 index increased to 90%. Conclusions For the first time, we report the detection of HPV45 in a case of ANEC. To our belief, PIK3CA mutations have also not been previously demonstrated in this tumor entity. In highly malignant ANECs, cure can in rare cases be achieved. Although speculative, expression of HPV45 and/or the PIK3CA mutation may have contributed to the favorable outcome.