Chemotherapy-induced persistent serpentine supra-venous hyperpigmented eruption and persistent supra-venous erythematous eruption: case report.

This paper presents the case of an 85-year-old male affected by classic Kaposi's sarcoma (CKS) since 1994. The disease was widespread over much of the skin surface. Since 1995 the patient had undergone several chemotherapy treatments with good, but not lasting results. Due to a worsening in the pathology, in October 2005 the patient was prescribed a further cycle of vinorelbine. Twenty-four hours after the first infusion, followed by isotonic sodium chloride solution vein wash, a supra-venous serpentine erythematous lesion appeared directly above infusion site. The lesion extended centripetally from the injection point and involved the whole supra-venous area. Over the following days, a gradual variation in lesion colour, from erythematous to hyperpigmented, was observed. Given this clinical and histological picture, the diagnosis of persistent serpentine supra-venous hyperpigmented eruption (PSSHE) was made. Draft of a rare secondary effect whose pathogenesis still remain to explain. The literature holds reports of another skin manifestation with similar supra-venous characteristics: persistent supra-venous erythematous eruption (PSSE), clinical entity that enters in differential diagnosis with the PSSHE. Many of the drugs used in chemotherapy have been indicated as responsible for these peculiar side-effects. To the authors' knowledge, the literature reports only one PHSSE case induced by i.v. vinorelbine infusion.

Molecular alterations at chromosome 9p21 in melanocytic naevi and melanoma.

BACKGROUND: The chromosome 9p21 and its CDKN locus, with the p16 tumour suppressor gene (CDKN2A), are recognized as the genomic regions involved in the pathogenesis of melanoma. OBJECTIVES: To elucidate further the role of such regions during the different phases of melanocytic tumorigenesis. METHODS: Tissue sections from naevi, primary and metastatic melanomas were investigated by fluorescence in situ hybridization for allelic loss at the 9p21 chromosome and by immunochemistry for p16CDKN2A expression. RESULTS: Dysplastic naevi and primary or secondary melanomas were found to carry hemizygous deletions within the entire 9p21 region at similar frequencies (varying from 55% to 62%). Allelic deletion spanning the CDKN locus was observed at significantly increased rates moving from early (7%) to advanced (28%) primary melanomas and to secondary melanoma lesions (37%) (P=0.018). Also, inactivation of the p16 gene (CDKN2A) was absent in naevi and present at steadily increasing rates moving from primary melanomas (7% early lesions to 17% advanced lesions) to melanoma metastases (62%) (P=0.004). CONCLUSIONS: Our findings indicate that, in a model of sequential accumulation of genetic alterations, 9p21 deletions may play a role in melanocytic transformation and tumour initiation whereas rearrangements at the CDKN locus, and p16 gene (CDKN2A) inactivation may contribute to tumour progression.

Mycobacterium avium sub. paratuberculosis in tissue samples of Crohn's disease patients.

Crohn's disease is a non-specific chronic transmural inflammatory disease. The disease was associated with a frameshit mutation in the NOD2 gene. Nevertheless, other researchers associated the presence of M. paratuberculosis within the intestinal tissues of patients with the disease. An adapted "in situ hybridization" technique was used to detect IS900 M. paratuberculosis DNA in paraffin embedded tissue from Crohns tissue disease samples. We were able to identify M. paratuberculosis DNA in around 69% of the paraffine embedded intestinal samples of Crohn's disease patients analysed. The presence of M. paratuberculosis DNA in the intestinal samples analysed does not necessarily mean that M. paratuberculosis is responsible for Crohn's disease. Our results support the hypothesis that infection may be caused by cell wall defective M. paratuberculosis since no bacteria were detected by Ziehl Neelsen stain.

Identification of Mycobacterium avium subsp. paratuberculosis in biopsy specimens from patients with Crohn's disease identified by in situ hybridization.

Crohn's disease is a chronic inflammatory disease of the gastrointestinal tract of unknown etiology. We report on the presence of cell wall-deficient Mycobacterium avium subsp. paratuberculosis in 35 of 48 paraffin-embedded tissue specimens from 33 patients with Crohn's disease by in situ hybridization with IS900 as a probe.

Detection of occult melanoma cells in paraffin-embedded histologically negative sentinel lymph nodes using a reverse transcriptase polymerase chain reaction assay.

PURPOSE: Detection of occult metastasis before the development of clinical disease could allow more accurate staging, appropriate follow-up procedures, and adjuvant therapies in patients with malignant melanoma (MM). The sentinel lymph node (SLN) has been proposed as a reliable predictor of metastatic disease in the lymphatic basin draining the primary melanoma. In this study, we screened both paraffin-embedded SLNs and peripheral-blood (PB) samples from MM patients at various stage of disease using a multimarker reverse transcriptase polymerase chain reaction (RT-PCR) assay. The prognostic significance of the presence of PCR-positive markers was also evaluated. PATIENTS AND METHODS: Total RNA was obtained from paraffin-embedded SLN sections and PB samples of 75 MM patients. RT-PCR was performed using tyrosinase and MelanA/MART1 as melanoma-associated markers. Radiolabeled PCR products were analyzed on denaturing polyacrylamide gels. RESULTS: Good sensitivity of the RT-PCR assay on archival tissues was demonstrated after comparison of RT-PCR results on frozen and paraffin-embedded SLNs from 16 MM patients. Significant correlation between the disease stage and marker expression in both PB and SLN samples was observed; the highest value was for patients who were positive for both markers in SLN (P =.006). Progression of disease was significantly associated with the total number of PCR-positive markers in both PB (P =.034) and SLN (P =.001) samples. CONCLUSION: Although sensitivity is lowered by the use of paraffin-embedded specimens, our data indicate that RT-PCR analysis of serial sections from archival SLNs may be helpful in improving detection of occult micrometastases, thus improving staging of patients with melanoma.

Clinical significance of PCR-positive mRNA markers in peripheral blood and regional nodes of malignant melanoma patients. Melanoma Cooperative Group.

Reverse-transcriptase polymerase chain reaction (RT-PCR) with multiple markers has been demonstrated to be highly sensitive in detecting metastatic cells in peripheral blood of malignant melanoma (MM) patients, and the circulating MM cells to be significantly correlated with disease stages. We further evaluated the presence of specific PCR-positive mRNA markers in peripheral blood as well as in regional nodes as an expression of tumor progression. Peripheral blood samples from 317 MM patients with either localized (n = 219) or metastatic (n = 98) disease were processed to obtain total cellular RNA. RT-PCR was performed using tyrosinase (TYR), p97, and MelanA/MART1 as mRNA markers. PCR products were analyzed by gel electrophoresis and Southern blot hybridization. In addition, paraffin-embedded samples of histologically proven tumor-negative lymph nodes from the subset of patients with localized disease were analyzed by RT-PCR, using radiolabeled primers for TYR and MelanA/MART1. The presence of mRNA markers was significantly correlated with tumor burden with a good correlation between risk of recurrence (evaluated in stage I-III patients) and increasing number of PCR-positive markers (p = 0.0002). Currently, for each patient, PCR results obtained at different times during follow-up are being analyzed, and any variation in the number of PCR-positive markers is being correlated to the clinical status. Molecular screening of histologically negative nodes for the presence of metastatic MM cells is also under evaluation. Preliminary assessment of a subset of MM patients with higher risk of recurrence will require longer follow-up in order to define the role of RT-PCR in monitoring these patients.

Definition of the role of chromosome 9p21 in sporadic melanoma through genetic analysis of primary tumours and their metastases. The Melanoma Cooperative Group.

Malignant melanoma (MM) is thought to arise by sequential accumulation of genetic alterations in normal melanocytes. Previous cytogenetic and molecular studies indicated the 9p21 as the chromosomal region involved in MM pathogenesis. In addition to the CDKN genes (p16/CDKN2A, p15/CDKN2B and p19(ARF), frequently inactivated in familial MM), widely reported data suggested the presence within this region of other melanoma susceptibility gene(s). To clearly assess the role of the 9p21 region in sporadic melanoma, we evaluated the presence of microsatellite instability (MSI) and loss of heterozygosity (LOH) in primary tumours as well as in synchronous or asynchronous metastases obtained from the same MM patients, using 9 polymorphic markers from a 17-cM region at 9p21. LOH and MSI were found in 27 (41%) and 11 (17%), respectively, out of 66 primary tumours analysed. In corresponding 58 metastases, MSI was found at higher rate (22; 38%), whereas a quite identical pattern of allelic deletions with 27 (47%) LOH+ cases were observed. Although the CDKN locus was mostly affected by LOH, an additional region of common allelic deletion corresponding to marker D9S171 was also identified. No significant statistical correlation between any 9p21 genetic alteration (LOH, MSI or both) and clinicopathological parameters was observed.

[Kikuchi's disease and proteinaceous lymphoadenopathy in 4 patients with HIV infection]. / Malattia di Kikuchi e linfoadenopatia proteinacea in quattro pazienti on infezione da HIV.

In the lymphadenopathy occurring in the acquired immunodeficiency syndrome (AIDS) and the AIDS related complex (ARC), consistent histologic patterns have been described with some variants thereof, such as angioimmunoblastic lymphadenopathy-like or Castleman disease-like. In four such patients we have observed two other types of nodal lesions. Three patients had lymph node biopsies showing the characteristic histologic and immunophenotypic features of histiocytic necrotizing lymphadenitis (Kikuchi's disease). These were two males, 26 and 35-year old, with bilateral axillary and cervical lymphadenopathy, respectively, and one female, 29-years old with peripheral and abdominal lymphadenopathy. One patient had proteinaceous lymphadenopathy. This was a 26-year old man with disseminated lymphadenopathy and a small monoclonal IgG/k peak in the serum. Whether these two processes are direct effects of the HIV virus on the immune system or due to intercurrent etiologic factors, has to be determined. These observations, however, indicate that the range of nodal lesions (that the pathologist may encounter) in AIDS/ARC is wider than previously reported.