Nephrogenic systemic fibrosis: late skin manifestations.

BACKGROUND: Nephrogenic systemic fibrosis (NSF) is a serious disease that occurs in patients with severe renal disease and is believed to be caused by gadolinium-containing contrast agents. A detailed description of the late skin manifestations of NSF is important to help dermatologists and nephrologists recognize the disease. OBSERVATIONS: We studied 17 patients with NSF late in the disease. All patients showed epidermal atrophy and hairlessness of the affected regions, primarily the lower legs. Affected areas were symmetrically distributed and hyperpigmented in most cases. Eleven patients showed confluent dermal plaques with thickening and hardening. In contrast, 3 patients presented with wrinkled, redundant skin as seen in cutis laxa. Patients with NSF had significantly poorer scores than control patients on the Daily Life Quality Index (mean [SD], 11. 4 [7.4] vs 1.5 [2. 3]; P < .001). CONCLUSIONS: This descriptive case series of patients with NSF gives a detailed clinical picture of the skin manifestations late in the disease. It demonstrates that the clinical picture in the late stage has a varied presentation and that NSF has a significant effect on the quality of life.

Nephrogenic systemic fibrosis: a serious iatrogenic disease of renal failure patients.

Nephrogenic systemic fibrosis (NSF) is a fibrotic disease seen in renal failure patients that may lead to severe physical disability. It has been demonstrated in recent studies that NSF can be caused by some gadolinium-containing MRI contrast agents. In this report we present one of a total of 26 cases of gadodiamide-related NSF from our hospital.

Cytopathologic diagnoses of fine-needle aspirations from endoscopic ultrasound of the mediastinum: reproducibility of the diagnoses and representativeness of aspirates from lymph nodes.

BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration biopsy through the esophagus (EUS-FNA) or the bronchial tree (endobronchial ultrasound guided transbronchial needle aspiration [EBUS-TBNA]) may be used to obtain specimens from mediastinal structures. The accuracy of this procedure has been well documented. However, no studies have studied the reproducibility of the pathologic assessment of the aspirated material. METHODS: A total of 102 slides from EUS-FNA or EBUS-TBNA were assessed 2 times by 4 pathologists who classified each slide to 1 of 5 diagnostic categories and judged if the aspirate came from a lymph node. Between the 2 rounds the criteria to be used in the assessment of the slides were reviewed in a limited education session. The 4 observers had at least 15 years of pathology experience, but their experience in EUS-FNA and/or EBUS-TBNA varied from almost none to more than 10 years. The kappa statistic was applied for the analysis of reproducibility. RESULTS: The reproducibility of the diagnoses in the first round was good to excellent (kappa, 0.52-0.89). The teaching session led to a significant improvement of the reproducibility between the least and the most experienced observers (kappa ranges of 0.52-0.55 in the first round improved to 0.65-0.71 in the second round). CONCLUSIONS: The reproducibility of the diagnosis on EBUS-TBNA and EUS-FNA is excellent among pathologists experienced with these types of samples. Pathologists who are generally experienced but have little experience with EBUS-TBNA and EUS-FNA show a steep learning curve. From a pathologic point of view, EBUS-TBNA and EUS-FNA are feasible, but only experienced pathologists should do the assessments.

Case-control study of gadodiamide-related nephrogenic systemic fibrosis.

BACKGROUND: Nephrogenic systemic fibrosis may be caused by gadolinium (Gd)-containing magnetic resonance imaging contrast agents. Most reported cases were associated with one particular agent, gadodiamide. Yet, unidentified cofactors might explain why only a minority of renal failure patients exposed to gadodiamide develop nephrogenic systemic fibrosis. METHODS: We conducted a case-control study of 19 histologically verified cases and 19 sex- and age-matched controls. All subjects had chronic renal failure when exposed to gadodiamide. Clinical, biochemical and pharmacological data were retrieved from medical records. RESULTS: Cases had been exposed to a mean gadodiamide dose of 0.29 mmol/kg (range 0.18-0.50) shortly before first signs of nephrogenic systemic fibrosis. Controls had been exposed to 0.28 mmol/kg (0.13-0.49). Cumulative gadodiamide exposure while in chronic kidney disease stage 5 was significantly higher among cases compared with controls (0.41 vs 0.31 mmol/kg, P = 0.05) and among severe cases (n = 9) compared with non-severe cases (0.49 vs 0.33 mmol/kg, P = 0.02). Severe cases developed primarily among patients in regular haemodialysis therapy at exposure. Cases had higher serum concentrations of ionized calcium and phosphate than controls and tended to receive higher doses of epoietin-beta than controls at time of exposure. Severe cases were treated with higher doses of epoietin-beta than non-severe cases at exposure (10.8 vs 4.4 10(3) IU/week, P = 0.02). CONCLUSIONS: Increasing cumulative gadodiamide exposure, high-dose epoietin-beta treatment, and higher serum concentrations of ionized calcium and phosphate increase the risk of gadodiamide-related nephrogenic systemic fibrosis in renal failure patients. Severe cases seem to develop primarily among patients in regular haemodialysis therapy at exposure.

Poppyfield bleeding: a new dermatoscopic sign and its histopathological background.

Dermatoscopy increases the accuracy of diagnosis of melanoma. An atypical vascular pattern may be an indicator of cutaneous malignant melanoma (CMM). During dermatoscopy of certain CMMs numerous ruby droplets of blood appear when the dermatoscope is pressed firmly against the lesion. The aim of this paper was to examine the histopathological background for this observation. CMMs from 8 patients showing the poppyfield sign, i.e. squirts of ruby blood droplets, were paired with 8 CMMs of equal Breslow thickness not showing this sign. The 16 CMMs were placed in an unsystematic sequence and presented to two dermato-pathologists who assessed the lesions independently for confirmation of Breslow thickness, Clark level, ulceration and presence of dilated tumour vessels. There was no disagreement between the pathologists' assessments. Age of the patients and Breslow thickness of the cutaneous malignant melanoma were similar in the two groups. All 8 poppyfield CMMs had dilated tumour vessels compared with 25% (2/8) of the non-poppyfield CMMs (p< 0.007). Histological ulceration was observed in all poppyfield CMMs and none of the non-poppyfield CMMs (p< 0.001). The poppyfield bleeding sign is a dermatoscopic clue to dilated tumour vessels. It may be a dermatoscopic reflection of increased vascular density described in primary CMMs compared with adjacent skin and may also reflect the presence of primitive vessels in CMMs displaying increased fragility.

Effect of UV irradiation on cutaneous cicatrices: a randomized, controlled trial with clinical, skin reflectance, histological, immunohistochemical and biochemical evaluations.

The aim of this study was to examine the effect of ultraviolet (UV) irradiation on human cutaneous cicatrices. In this randomized, controlled study, dermal punch biopsy wounds served as a wound healing model. Wounds healed by primary or second intention and were randomized to postoperative solar UV irradiation or to no UV exposure. Evaluations after 5 and 12 weeks included blinded clinical assessments, skin reflectance measurements, histology, immunohistochemistry, and biochemical analyses of the N-terminal propeptide from procollagen-1, hydroxyproline, hydroxylysine, and proline. Twelve weeks postoperatively, UV-irradiated cicatrices healing by second intention: (i) were significantly pointed out as the most disfiguring; (ii) obtained significantly higher scores of colour, infiltration and cicatrix area; and (iii) showed significantly higher increase in skin-reflectance measurements of skin-pigmentation vs. non-irradiated cicatrices. No histological, immunohistochemical or biochemical differences were found. In conclusion, postoperative UV exposure aggravates the clinical appearance of cicatrices in humans.

Procollagen 1 - a marker of fibroblastic and fibrohistiocytic skin tumors.

BACKGROUND: When dealing with tumors of presumed fibroblastic or fibrohistiocytic origin, immunohistochemistry is traditionally done to exclude a tumor of non-fibroblastic or non-fibrohistiocytic nature, because a reliable marker of fibroblastic or fibrohistiocytic cell origin is still to be introduced. This study investigates whether procollagen 1 is a useful marker of skin tumors composed of cells derived from fibroblasts or fibrohistiocytes. MATERIALS AND METHODS: Twenty-nine different types of skin tumors, including tumors composed of spindle cells as well as some additional epithelial and melanocytic tumors, were stained immunohistochemically with antibodies against procollagen 1. The total number of cases tested was 154. RESULTS: Tumors composed of cells of fibroblastic or fibrohistiocytic origin in general showed a high expression of procollagen 1, whereas tumors composed of non-fibroblastic cells in general showed no expression. However, there were a few exceptions, e.g., leiomyosarcoma and desmoplastic melanoma. CONCLUSIONS: The study suggests that immunohistochemical staining for procollagen 1 is a valuable marker for skin tumors composed of spindle cells derived from fibroblasts or fibrohistiocytes. However, in cases of spindle cell tumors with a morphology suggesting malignancy, it is recommended to use a panel of antibodies, which besides procollagen 1 includes markers such as S100, CD68, CD34, h-caldesmon, and pancytokeratin.

Nephrogenic systemic fibrosis: suspected causative role of gadodiamide used for contrast-enhanced magnetic resonance imaging.

Nephrogenic systemic fibrosis is a new, rare disease of unknown cause that affects patients with renal failure. Single cases led to the suspicion of a causative role of gadodiamide that is used for magnetic resonance imaging. This study therefore reviewed all of the authors' confirmed cases of nephrogenic systemic fibrosis (n = 13) with respect to clinical characteristics, gadodiamide exposure, and subsequent clinical course. It was found that all had been exposed to gadodiamide before the development of nephrogenic systemic fibrosis. The delay from exposure to first sign of the disease was 2 to 75 d (median 25 d). Odds ratio for acquiring the disease when gadodiamide exposed was 32.5 (95% confidence interval 1.9 to 549.2; P < 0.0001). Seven (54%) patients became severely disabled, and one died 21 mo after exposure. No other exposure/event than gadodiamide that was common to more than a minority of the patients could be identified. These findings indicate that gadodiamide plays a causative role in nephrogenic systemic fibrosis.

CD56+ lymphoma with skin involvement: clinicopathologic features and classification.

BACKGROUND: Extranodal lymphomas expressing CD56 (neuronal cell adhesion molecule) are characterized by a high incidence of cutaneous involvement and a very aggressive clinical course. Knowledge about the prognosis and clinicopathologic features of CD56(+) lymphomas with skin involvement is very limited. OBJECTIVES: To determine survival and prognostic factors for extranodal CD56(+) lymphomas with skin involvement and to describe their clinicopathologic features. DESIGN: Retrospective literature survey and case studies. PATIENTS: A total of 181 patients with CD56(+) lymphoma involving the skin: 177 cases from the literature and 4 new cases. MAIN OUTCOME MEASURE: Survival and its dependence on the following putative prognostic factors: staging, histopathologic findings, lymphocyte markers, T-cell receptor gene rearrangement, Epstein-Barr virus infection, treatment modality. RESULTS: Three major subtypes of CD56(+) lymphoma in the skin were distinguished: blastic lymphoma, nasal-type natural killer-cell/T-cell lymphoma, and subcutaneous panniculitislike lymphoma. The disease disseminated readily, mainly to lymph nodes, bone marrow, the central nervous system, and the liver, but 45% of patients had a purely cutaneous disease at presentation. All subtypes had a very aggressive course with a median survival of 14 months. The main risk factors were age older than 55 years (hazard ratio [HR], 2.5; 95% confidence interval [CI], 1.8-3.2), systemic dissemination at presentation (HR, 2.0; 95% CI, 1.5-3.3), and lack of CD30 (HR, 3.8; 95% CI, 1.4-4.9) or CD4 expression (HR, 1.56; 95% CI, 1.06-2.57). The different treatment modalities did not improve survival. CONCLUSIONS: CD56(+) lymphomas involving the skin are rare and extremely aggressive regardless of their histologic presentation and the extent of skin involvement. No effective treatment is available. The risk of death is particularly increased in older patients with CD30(-)CD4(-) lymphomas.

Melanoma diagnosis by Raman spectroscopy and neural networks: structure alterations in proteins and lipids in intact cancer tissue.

Melanoma is the most aggressive skin cancer. The specificity and sensitivity of clinical diagnosis varies from around 40% to 80%. Here, we investigated whether the chemical changes in the melanoma tissue detected by Raman spectroscopy and neural networks can be used for diagnostic purposes. Near-infrared Fourier transform Raman spectra were obtained from samples of melanoma (n=22) and other skin tumors that can be clinically confused with melanoma: pigmented nevi (n=41), basal cell carcinoma (n=48), seborrheic keratoses (n=23), and normal skin (n=89). A sensitivity analysis of spectral frequencies used by a neural network was performed to determine the importance of the individual components in the Raman spectra. Visual inspection of the Raman spectra suggested that melanoma could be differentiated from pigmented nevi, basal cell carcinoma, seborrheic keratoses, and normal skin due to the decrease in the intensity of the amide I protein band around 1660 cm-1. Moreover, melanoma and basal cell carcinoma showed an increase in the intensity of the lipid-specific band peaks around 1310 cm-1 and 1330 cm-1, respectively. Band alterations used in the visual inspection were also independently identified by a neural network for melanoma diagnosis. The sensitivity and specificity for diagnosis of melanoma achieved by neural network analysis of Raman spectra were 85% and 99%, respectively. We propose that neural network analysis of near-infrared Fourier transform Raman spectra could provide a novel method for rapid, automated skin cancer diagnosis on unstained skin samples.

Bone marrow precursor of extranodal T-cell lymphoma.

The development of extranodal lymphomas is thought to be initiated by the transformation event in peripheral organs. Lymphomatoid papulosis (LyP) is a low-grade cutaneous lymphoma and may progress into the cutaneous anaplastic lymphoma. We identified 2 patients who 3 and 4 years before the development of LyP were treated for an unrelated malignancy (Burkitt lymphoma and small-cell B-cell lymphoma). We analyzed the T-cell receptor (TCR) gene rearrangement pattern in their skin, blood, and bone marrow, including the archival bone marrow sampled years before the development of clinically evident LyP. In all samples we detected the unique monoclonal TCR rearrangements. This observation suggests that the initial malignant transformation in LyP occurred in bone marrow and not, as could be supposed, in the skin.

Histopathologic parameters in the evaluation of T1 squamous cell carcinomas of the oral cavity.

BACKGROUND: Prognostic indicators that could assist in a more precise selection of patients with small oral carcinomas for differentiated therapy would be valuable. A significant fraction of patients with stage I disease have a relatively poor prognosis despite the small size of the tumor, but in general stage I tumors of the oral cavity have a favorable prognosis. METHODS: Seventy-eight patients with stage I (T1N0M0) oral squamous cell carcinoma from two different ENT departments were included in the study. The pretreatment biopsy specimens were graded according to the modified classification of Jakobsson et al. Eight individual parameters were recorded, four parameters describing the tumor cell population and four parameters describing the tumor/host interaction. RESULTS: The only significant prognostic parameter for disease-specific survival was "mode of invasion." The histologic mean score was not significantly correlated to disease-specific or crude survival. CONCLUSIONS: Mode of invasion is the most important histologic parameter when evaluating the prognosis. Histologic evaluation of small squamous cell carcinomas of the oral cavity may assist the design of a differentiated treatment strategy (eg, monotherapy vs combined treatment).