Primary Cutaneous Neuroendocrine Tumor of the Vulva: A Case Report.

Primary cutaneous neuroendocrine tumors (CNET) are extremely rare. Only a few cases have been reported so far. CNET have an indolent clinical course and usually present as a single flesh-colored nodule with a predilection for the scalp and trunk in elderly patients.

Presence of Skin Tissue-Resident Memory T Cells in Human Nonmalignant and Premalignant Melanocytic Skin Lesions and in Melanoma.

The infiltration of tissue-resident memory (TRM) cells in melanoma correlates with improved survival, suggesting an important role for TRM cells in immunity against melanoma. However, little is known about the presence of TRM cells in nonmalignant and premalignant melanocytic lesions. This study aimed to evaluate the presence of TRM cells in human skin melanocytic lesions, representing the spectrum from healthy skin to metastatic melanoma.

Limited impact of COVID-19-related diagnostic delay on cutaneous melanoma and squamous cell carcinoma tumour characteristics: a nationwide pathology registry analysis.

Background: The COVID-19 pandemic reduced the number of skin cancer diagnoses, potentially causing a progression to unfavourable tumour stages.

Objectives: To identify the impact of delayed diagnostics on primary invasive melanoma and cutaneous squamous cell carcinoma (cSCC) by comparing tumour (pT) stage, Breslow thickness and invasion depth from before to after the first and second lockdown periods.

Methods: In this population-based cohort study, histopathology reports registered between 1 January 2018 and 22 July 2021 were obtained from the nationwide histopathology registry in the Netherlands.

Renal cancer and pneumothorax risk in Birt-Hogg-Dubé syndrome; an analysis of 115 FLCN mutation carriers from 35 BHD families.

Background: Birt-Hogg-Dubé (BHD) syndrome is an autosomal dominant condition caused by germline FLCN mutations, and characterised by fibrofolliculomas, pneumothorax and renal cancer. The renal cancer risk, cancer phenotype and pneumothorax risk of BHD have not yet been fully clarified. The main focus of this study was to assess the risk of renal cancer, the histological subtypes of renal tumours and the pneumothorax risk in BHD.

Familial multiple discoid fibromas: a look-alike of Birt-Hogg-Dubé syndrome not linked to the FLCN locus.

Background: Previously, we proposed that familial multiple trichodiscomas (OMIM 190340) is distinct from Birt-Hogg-Dubé syndrome (BHD) (OMIM #135150). BHD is characterized by multiple fibrofolliculomas/trichodiscomas, lung cysts, pneumothorax, and renal cell cancer. Germline FLCN mutations can be detected in most but not all BHD families.

Russell bodies in a skin biopsy: a case report.

Introduction: The presence of eosinophilic bodies in a skin biopsy can be found in a variety of situations and this may present a challenge to the pathologist. The differential diagnosis of these eosinophilic structures include microorganisms such as histoplasmosis or cryptococcosis, fungi, Michaelis-Gutmann bodies, deposits of amyloid or immunoglobulins, colloid bodies or elastic bodies.

Case Presentation: During a routine examination of a skin biopsy with actinic keratosis taken from the cheek of a 61-year-old man, clusters of eosinophilic bodies were seen within an inflammatory infiltrate in the dermis, both intracytoplasmic and extracellular.

Birt-Hogg-Dubé syndrome: clinical and genetic studies of 20 families.

Birt-Hogg-Dubé syndrome (BHD) is an autosomal-dominant genodermatosis characterized by skin fibrofolliculomas and an increased risk of spontaneous pneumothorax, renal and possibly other tumors. A causative gene (FLCN) on chromosome 17p has recently been identified. We here report clinical and genetic studies of 20 BHD families ascertained by the presence of multiple fibrofolliculomas or trichodiscomas in the proband.

[The immune system of the skin and stereotyped reaction patterns in inflammatory skin diseases].

The clinical and histological presentation of inflammatory disease in the skin is exceedingly heterogeneous. Nonetheless, most inflammatory dermatoses can be classified according to five stereotypical tissue-reaction patterns: the spongiotic, the lichenoid, the psoriasiform, the vesiculo-bullous and the vasculopathic. By means of potent antigen-presenting cells, cytokine and chemokine cascades and a skin-specific cutaneous lymphocyte antigen (CLA)-positive lymphocyte population, the skin is able to respond very efficiently to pathogens that threaten the individual.

[Three patients with a Spitz naevus that later turned out to be a melanoma].

A melanocytic lesion was removed from each of three patients: 2 men aged 37 and 65 and 1 woman aged 45. The preferred diagnosis was 'Spitz naevus'. Subsequently, all three developed regional (sub)cutaneous and/or lymph node metastases, indicating that the lesions were melanomas.

Metastasectomy and active specific immunotherapy for a large single melanoma metastasis.

A patient with a large duodenal melanoma metastasis, involving adjacent jejunum and colon, is presented. Treatment consisted of a combination of radical surgery and active specific immunotherapy by means of an autologous tumor cell vaccine and BCG after which a recurrence-free survival of now more than 10 years has been observed. The role of surgery and immunotherapy in the treatment of metastatic melanoma are discussed.

A genome-activating N-terminal coat protein peptide of alfalfa mosaic virus is able to activate infection by RNAs 1, 2 and 3 but not by RNAs 1 and 2. Further support for the messenger release hypothesis.

An N-terminal genome-activating peptide of 25 amino acid residues of alfalfa mosaic virus coat protein was unable to activate the incomplete viral genome consisting of RNAs 1 and 2. The messenger release hypothesis predicts that RNA 3 must complement such an inoculum in order to produce RNA 4 that will trigger the process. This is shown indeed to be the case.

Natural minus-strand RNAs of alfalfa mosaic virus as in vitro templates for viral RNA polymerase. 3'-terminal non-coded guanosine and coat protein are insufficient factors for full-size plus-strand synthesis.

Replication complexes of alfalfa mosaic virus produce in vivo large quantities of plus-strand RNAs, but this production is fully dependent on the presence of coat protein. In order to study this process of RNA-dependent and coat protein-regulated RNA synthesis we have isolated the three natural minus-strand RNAs (containing any posttranscriptional modification that might have occurred) and have tested them for coat protein binding sites and template activity in an in vitro system with the viral RNA polymerase. The enzyme was prepared by an advanced isolation procedure.

All infiltrating T-lymphocytes in Hodgkin's disease express immunohistochemically detectable T-cell receptor zeta-chains in situ.

Aim: We studied the expression of TCR zeta-chain on tumour-infiltrating lymphocytes in EBV-positive and EBV-negative cases of Hodgkin's disease (HD), to assess whether downregulation of TCR zeta-chain on tumour-infiltrating lymphocytes might be a mechanism for immune escape of the neoplastic cells.

Methods And Results: By immunohistochemistry we investigated tissue of 27 cases of primary HD, both paraffin embedded and frozen, for the presence of T-cell receptor complex zeta-chain and other T-cell markers on the reactive cells. Strong membranous staining of TCR zeta-chain was present in all cases in frozen tissue.

Activation of the alfalfa mosaic virus genome by viral coat protein in non-transgenic plants and protoplasts. The protection model biochemically tested.

In non-transgenic host plants and protoplasts alfalfa mosaic virus displays a strong need for coat protein when starting an infection cycle. The "protection model" states that the three viral RNAs must have a few coat protein subunits at their 3' termini in order to protect them in the host cell against degradation by 3'- to- 5' exoribonucleases [Neeleman L, Van der Vossen EAG, Bol JF (1993) Virology 196: 883-887]. We demonstrated that the naked genome RNAs are slightly infectious, if the inoculation is done at very high concentrations, or if it is preceded by an additional inoculation with the RNAs 1 and 2 (encoding subunits for the viral RNA polymerase).

Genome activation in alfamo- and ilarviruses.

Alfamo- and ilarviruses are characterized by the deficiency of their genomes (three messenger-sense RNAs) to start an infection cycle. The RNAs are in capsids built from a single species of protein of about 24 kD. A few dimers of this coat protein per RNA molecule are sufficient to activate the genome.

A core promoter hairpin is essential for subgenomic RNA synthesis in alfalfa mosaic alfamovirus and is conserved in other Bromoviridae.

The nucleotide sequence immediately in front of the initiation site for subgenomic RNA 4 synthesis on RNA 3 minus strand, which has been proved to function as a core promoter, was inspected for secondary structure in 26 species of the plant virus family Bromoviridae. In 23 cases a stable hairpin could be predicted at a distance of 3 to 8 nucleotides from the initiation site of RNA 4. This hairpin contained several conserved nucleotides that are essential for core promoter activity in brome mosaic virus (R.

Regulation of single-strand RNA synthesis of alfalfa mosaic virus in non-transgenic cowpea protoplasts by the viral coat protein.

We have compared the RNA synthesis of alfalfa mosaic virus in complete (by RNAs 1, 2 and 3) and incomplete infections (by RNAs 1 and 2) of cowpea protoplasts. Both viral RNA polymerase activity and accumulation of viral RNA were measured. By annealing RNA in solution with 32P-labelled probes of plus and minus polarity followed by treatment with ribonucleases, we determined viral RNAs quantitatively in both single- and double-stranded RNA fractions.

Efficient transcription of the tRNA-like structure of turnip yellow mosaic virus by a template-dependent and specific viral RNA polymerase obtained by a new procedure [corrected].

The RNA-dependent RNA polymerase (RdRp) of turnip yellow mosaic virus (TYMV) was isolated by a simple, new method. An active, template-dependent and specific enzyme was obtained. Although the genomic RNA of TYMV could not be transcribed completely during an in vitro RdRp assay, a complete double-stranded product was obtained when a 3' terminal RNA fragment of 83 nucleotides was used as a template.

Interaction between RNA-dependent RNA polymerase of alfalfa mosaic virus and its template: oxidation of vicinal hydroxyl groups blocks in vitro RNA synthesis.

In the life cycle of a (+)-strand RNA plant virus the processes of template RNA recognition and initiation of the synthesis of a complementary strand by the viral RNA-dependent RNA polymerase (RdRp) are crucial early steps. Using a template-dependent in vitro RNA synthesizing system of alfalfa mosaic virus (AIMV) we were able to study the effect of small chemical modifications of the 3' end of the template RNAs on product formation. After oxidation of the 3'-terminal nucleoside of the template no products could be detected.

RNA duplex unwinding activity of alfalfa mosaic virus RNA-dependent RNA polymerase.

An RNA-dependent RNA polymerase (RdRp) purified from alfalfa mosaic virus-infected tobacco is capable of synthesizing in vitro full-size RNAs of minus and plus polarities. However, the enzyme is not able to perform a complete replication cycle in vitro. The products were found to be completely base-paired to their templates.