PCR testing for Treponema pallidum in paraffin-embedded skin biopsy specimens: test design and impact on the diagnosis of syphilis

Background: Syphilis, a chronic infection caused by Treponema pallidum (T. pallidum), is a disease which is increasing in incidence, and thus more and more becoming a differential diagnosis in routine pathology. Aim: Since histological changes are not specific, we sought to develop a polymerase chain reaction (PCR)-based molecular assay for the detection of T. pallidum in formalin-fixed, paraffin-embedded tissues, and evaluate its diagnostic power, especially in comparison with other ancillary methods, i.e. immunohistochemistry and Dieterle staining. Methods: 36 skin biopsies with the clinical and /or serological diagnosis of syphilis were evaluated by morphology, immunohistochemistry and s…

Wild-type JAK2 secondary acute erythroleukemia developing after JAK2-V617F-mutated primary myelofibrosis.

A 54-year-old female patient developed acute erythroleukemia after an 8-year course of primary myelofibrosis. The latter harbors the JAK2-V617F mutation and was treated with hydroxyurea and anagrelide. A bone marrow trephine biopsy disclosed 2 morphologically distinct areas of chronic primary myelofibrosis and acute erythroleukemia. Microdissection and a separate molecular pathological analysis was performed. Although the activating JAK2-V617F mutation was not maintained in blasts of acute erythroleukemia, it was detectable in the chronic phase of primary myelofibrosis, indicating that this mutation did not play a role in the leukemic transformation of erythroid cells.

Hepatitis E Virus Detection in Liver Tissue from Patients with Suspected Drug-Induced Liver Injury

Hepatitis E virus (HEV) infection is increasingly recognized as a cause of acute hepatitis in the industrialized world. We aimed to determine the frequency of acute Hepatitis E virus (HEV) infection in cases of suspected drug-induced liver injury (DILI), mainly a diagnosis of exclusion. To this aim, formalin-fixed, paraffin-embedded (FFPE) liver tissues of all cases routinely processed in our institute during a 2 ½ years period in which DILI was amongst the differential diagnoses (157 liver biopsies, one liver explant) were subjected to semi-nested RT-PCR for the detection of hepatitis E virus (HEV) RNA. Histopathology was re-evaluated on all cases tested positive. HEV RNA was detectable in…

Detection of RET rearrangements in papillary thyroid carcinoma using RT-PCR and FISH techniques - A molecular and clinical analysis.

Abstract Introduction Oncogenic BRAF and RAS mutations as well as multiple known (and yet unknown) RET fusion oncogenes comprise the majority of causative molecular alterations in papillary thyroid carcinoma (PTC). Apparently “mutation-negative” PTCs encompass a heterogenous group impeding analysis of prognostic significance of underlying genetics. Material and methods BRAF wild type PTC tissue of 56 patients was analyzed using two established methods: hybrid-specific RT-PCR for the predominant rearrangement RET/PTC1 and fluorescent in situ hybridization (FISH). Clinical features of the cases with and without RET rearrangement were compared (patient age, gender, tumor size, focality, lymph …

Transmission of angioimmunoblastic T-cell lymphoma by bone marrow transplant

Accidental transmission of lymphoma by bone marrow transplant is a rarely reported event [1–5], since candidates are only accepted for hematopoietic stem cell donation after a work-up that routinel...

ANKRD26-RET - A novel gene fusion involving RET in papillary thyroid carcinoma

Abstract Background Rearrangements of RET are drivers of oncogenesis, traceable in different cancer types as papillary thyroid carcinoma (PTC), non-small cell lung cancer, colorectal or breast cancer. Anchored multiplex PCR based next-generation sequencing (NGS) can detect RET rearrangements involving previously unknown partner genes. Methods A sample of PTC underwent NGS, following detection of RET rearrangement by fluorescence in situ hybridization. Expression analysis of ANKRD26 and RET was performed for the tumor harboring ANKRD26-RET, for corresponding normal thyroid tissue and PTC tumors with representative genetic alterations (BRAFV600E, CCDC6-RET), complemented by a comparative sear…

Novel rearrangements involving the RET gene in papillary thyroid carcinoma.

Abstract Background In the field of gene fusions driving tumorigenesis in papillary thyroid carcinoma (PTC), rearrangement of the proto-oncogene RET is the most frequent alteration. Apart from the most common rearrangement of RET to CCDC6, more than 15 partner genes are yet reported. The landscape of RET rearrangements in PTC (“RET-PTC”) can notably be enlarged by modern targeted next-generation sequencing, indicating similarities between oncogenic pathways in other cancer types with identical genetic alterations. Methods Targeted next-generation sequencing was performed for two cases of BRAF-wild type PTC with confirmation of the results by Sanger sequencing. A “UniProt” database research …

Bone Marrow Findings in Multicentric Castleman Disease in HIV-negative Patients

Because bone marrow histology in multicentric Castleman disease in human immunodeficiency virus-negative patients is not well reported, we investigated sequential bone marrow biopsies of 3 affected human immunodeficiency virus-negative patients, of which one was human herpes virus 8 (HHV8)-positive. The histologic evaluation of the bone marrow revealed lymphoid follicles with regressed germinal centers in 1 patient. Another patient showed tumorlike but bland polyclonal plasmacytosis with large perivascular plasma cell clusters. The HHV8-positive patient revealed interstitial HHV8-positive cells accompanied by a mild plasmacytosis. The atypical lymphoid follicles could be regarded as a bone …

Swelling of the buccal cheek: an unusual presentation of primary tuberculosis.

PD-L1 Expression and Immune Cell Infiltration in Gastroenteropancreatic (GEP) and Non-GEP Neuroendocrine Neoplasms With High Proliferative Activity

The potential of neuroendocrine neoplasms (NEN) to respond to checkpoint inhibitors is largely unknown and full of great expectations. Immunohistochemical (IHC) studies of programmed cell death ligand 1 (PD-L1) expression in the tumor microenvironment and its implications in predicting the response to checkpoint inhibition is a very active subject. Currently, the combined analysis of PD-L1 expression and tumor-associated immune cell (TAIC) infiltration is considered the best predictive marker of therapeutic response. Here we investigated the expression of PD-L1 on tumor cells (TC) and tumor-infiltrating immune cells (IC) by IHC in 68 NEN samples with a high proliferation rate (Ki-67 >20%…