Kyriaki Aroni

A study of the pathogenesis of rosacea: how angiogenesis and mast cells may participate in a complex multifactorial process.

In the present study we evaluated, in involved and clinically uninvolved skin of Rosacea, microvessels density (MVD) and total vascular area (TVA) in addition to multiple morphologic characteristics of microvessels and also mast cells (MCs) number. We examined also the relationship between angiogenesis, MCs number and disease clinicopathological data. The study included 69 patients with Rosacea. A skin biopsy with a 4-mm punch was performed from clinically involved skin in each case. In nine randomly selected patients, facial biopsy specimens were obtained from both involved and clinically uninvolved skin. Histological sections, immunostained for factor VIII, were evaluated by image analysis for the quantification of MVD, TVA and several morphometric parameters related to the vessel size or shape. MCs detection in the dermis was carried out using the chloracetate esterase method (Fast Blue RR) in parafin sections. Serum antibodies against H.pylori were detected. Statistically important differences concerning the factors of angiogenesis between lesional and clinically non-lesional skin were demonstrated. A statistical important correlation was found also between high vascular density, PPR clinical type and the presence of ocular manifestations. MVD or TVA showed no correlation with the degree of solar elastosis or inflammation and with the Demodex density as well. However, high MVD values were found to correlate with granuloma formation in the dermis. MCs number were significantly greater in lesional compared to clinically non-lesional skin. Statistical significance was shown between MCs density and disease duration. However, no correlation between MCs number and blood vessel density was found. Angiogenesis seems to play an important role in the pathogenesis especially of the more severe clinical form of Rosacea. MCs seem to participate in evolution to disease chronicity by contributing to inflammation, angiogenesis and tissue fibrosis.

Rosacea: A Clinicopathological Approach

Background: There are few reports of the histological changes in rosacea, and little attempt has been made to correlate such changes with clinical findings. In the present study, we describe in detail the histopathological features of rosacea in a large number of patients and simultaneously investigate the aetiopathogenesis of the disease based on the comparative assessment of epidemiological, clinical and histological findings. Methods: The study included 73 patients with rosacea. A skin biopsy with a 4-mm punch was performed in each case. All biopsy specimens included subcutaneous tissue. In 10 randomly selected patients, facial biopsy specimens were obtained from both involved and uninvolved (non-lesional) skin. Demodex mite presence was estimated semi-quantitatively under light microscopy. Patients with self-reported gastro-intestinal symptoms were submitted to upper gastro-intestinal endoscopy, and a rapid urease test was performed. Serological antibodies, IgG and IgA, against Helicobacter pylori were also detected. Results: The patients had a broad clinical spectrum of lesions. No specific histological features associated with either erythematous-telangiectatic or papulopustular clinical forms were noticed. Histological examination showed that there is no histological pattern unique to rosacea. Three different types of granulomas were observed: small palisaded ones around altered collagen and other granulomas of elastolytic and non-specific epithelioid type, all coexisting in 5 cases. The deep dermis and subcutis were frequently involved. Comparative study in 10 rosacea patients between lesional and non-lesional skin biopsies revealed almost the same histological changes to the latter biopsies, to a lesser degree though. Conclusion: Rosacea seems to be a reaction pattern to which a variety of pathogenetic routes may lead.

Distribution of lysozyme, a1-Antichymotrypsin and a1-Antitrypsin in adenocarcinomas of the stomach and large intestine

Lysozyme, a1-Antichymotrypsin and a1-Antitrypsin were demonstrated by an immunoperoxidase technique (PAP) in malignant cells of adenocarcinomas of the stomach but not of the large intestine. Lymph-node metastases showed identical immunoreactivity to that of the primary tumour. Neoplasms arising from the cardia, the body and the pyloric antrum of the stomach showed different immunostaining reactions: It seems that these differences partly reflect the distribution of lysozyme, a1-Antichymotrypsin and a1-Antitrypsin in the normal gastric mucosa. The usefulness of our findings in the identification of the primary tumour in cases of lymph node metastases of unknown origin, is also discussed.

Protective effect of a novel antioxidant non-steroidal anti-inflammatory agent (compound IA) on intestinal viability after acute mesenteric ischemia and reperfusion

Reactive oxygen species play an important role in the basic pathophysiology of ischemia-reperfusion injury. We investigated whether the administration of a novel non-steroidal anti-inflammatory compound with antioxidant properties, the compound [5-(2-amino-ethylamino)-1-phenyl-2-pentanone] (compound IA), has a beneficial effect on the repair process of the intestinal mucosa after transient mesenteric ischemia in a randomized blind trial. Six groups of rats were subjected to a model of 60 min of intestinal ischemia that was produced by occluding the superior mesenteric artery. At the end of ischemia, compound IA was administered intravenously and the clamp was removed allowing reperfusion. At 60 min after reperfusion, animals were sacrificed and a 10 cm section of terminal ileum was resected. The outcome was evaluated by histopathologic assessment, measurement of polymorphonuclear leukocytes and the extent of lipid peroxidation measuring the small intestine tissue malondialdehyde. After 1 h of reperfusion, the mucosal damage was less in IA-treated rats compared with the control group. Moreover, the number of polymorphonuclear leukocytes in intestinal mucosa was significantly lower in IA group. Compound IA resulted in a statistically significant reduction of the concentration of small intestine tissue malondialdehyde, compared to those of controls. Administration of compound IA decreased the mucosal damage in rats that were subjected to 60 min of ischemia followed by 60 min of reperfusion. The mechanism of compound IA action is considered to be mediated via its potent antioxidant, free radical scavenging activities and inhibition of polymorphonuclear leukocytes infiltration.

Polyneuropathy induced by HIV disease and antiretroviral therapy

OBJECTIVE To investigate the underlying mechanisms of polyneuropathy induced by HIV infection or antiretroviral drugs. METHODS We tested 100 HIV patients (59 with AIDS). Ninety-three patients received antiretroviral drugs. Forty-four were treated with neurotoxic compounds (ddI, ddC, d4T). Nerve conduction velocities and the sympathetic skin response (SSR) in palms and soles were measured in all patients. In skin biopsies (ankle and thigh), the intraepidermal nerve fiber density (IENFD) and the number of epidermal fibers without contact to the basal membrane (fragments) were quantified using PGP9.5 staining. RESULTS Severity of the disease (CD4 +count) correlated to conduction velocities of peroneal (p < 0.01, Spearmans rank correlation), sural (p < 0.01) and median nerves (p < 0.05/p < 0.001, sensory/motor). In contrast, the duration of neurotoxic treatment did not impair conduction velocities (p > 0.3) but correlated to reduced IENFD in the ankle (r = -0.24, p < 0.05). Despite their reduced IENFD, patients with long neurotoxic treatment had a high number of fragments irrespective of their CD4 +count. CONCLUSIONS Neurotoxic treatment appears to primarily impair thin fiber conduction, whereas HIV neuropathy is linked to large fiber impairment and reduction of fragments of nerve fibers. SIGNIFICANCE These findings emphasize the differential pattern of polyneuropathy in HIV patients caused by the infection or induced by antiretroviral treatment.

Signet Ring Basal Cell Carcinoma: A Case Study Emphasizing the Differential Diagnosis of Neoplasms with Signet Ring Cell Formation

Signet ring cells are cells in which the nucleus is crescentically compressed to the cellular border so that the cells look like signet rings. Due to the pluripotential nature of the basal cells of the epidermis, basal cell carcinoma displays many histopathological variants. We herein report the rare case of a middle-aged woman who had a basal cell carcinoma on the skin of the upper lip. The neoplasm was predominantly composed of cells with signet ring configuration. Histochemically, the latter were mucin-negative. Immunohistochemistry demonstrated intracytoplasmic reactivity for cytokeratin MNF116 with strong staining intensity, as well as for smooth muscle actin. The signet ring tumor cells were S100 protein-negative and carcinoembryonic antigen-negative. The lack of ploidy abnormality as well as of molecular alterations in K-ras and p53 genes may explain in part the non-aggressive biological behavior of the present tumor. Because of potential diagnostic difficulties, the pathologist should be aware of this unusual form of basal cell carcinoma. A brief review of the literature on the differential diagnosis of signet ring cell cutaneous tumors is presented.

An immunocytochemical study of the distribution of lysozyme, a1-antitrypsin and a1-antichymotrypsin in the normal and pathological gall bladder

We have studied the distribution of lysozyme (Ly), a1-antitrypsin (a1AT) and a1-antichymotrypsin (a1AChy) in the normal, chronically inflamed and neoplastic gall bladder mucosa using the peroxidase-anti-peroxidase (PAP) method. Ly was absent from the normal mucosa but it was found only in areas of glandular metaplasia of true antral type and in crypts of possible early metaplastic nature in cases of chronic cholecystitis. a1AT and a1AChy were also found in such metaplastic areas, but their presence was also observed immunohistochemically in areas of essentially normal and in non-metaplastic, chronically inflamed gall bladder mucosa. The possible local production of these substances by gall bladder epithelial cells is discussed. Ly, a1AT and a1AChy were also found in various histological types of adenocarcinoma of the gall bladder in varying degrees of frequency and intensity, unrelated to the histological type and invasiveness of the tumour.

IMMUNOHISTOCHEMISTRY IN HISTOID LEPROSY

Background. Histoid leprosy is a rare form of multibacillary leprosy as the result of secondary or even primary resistance to dapsone. The etiopathogenesis has not been clarified up to now.

Association between Microvessel Density and Histologic Grade in Renal Cell Carcinomas

Angiogenesis seems to contribute to tumor growth and the development of metastases. There may be an association between the vascular density of individual tumors and their prognosis. In the present survey we studied 53 cases of renal cell carcinoma investigating possible relationship between histologic grade and microvessel density (MVD) measured by an image analysis system. According to our results MVD was significantly associated with the histologic grade, higher grades being accompanied with a higher MVD. Further studies are needed to investigate a possible connection of MVD with the prognostic role of grade in RCCs.

Erythema dyschromicum perstans and hepatitis C virus infection.

A 48‐year‐old woman with a 10‐month history of widespread, hyperpigmented, slightly pruritic macules, with a red border, involving the trunk and the proximal limbs ( Fig. 1 ) was referred to our outpatient department. The oral mucosa, palms, soles, scalp, and nails were normal.