[A histological and immunohistological study of vascular and inflammatory changes in rosacea]. / Étude histologique et immunohistochimique des anomalies vasculaires et inflammatoires de la rosacée.

BACKGROUND: Rosacea has a number of pathophysiological components, chief of which are vascular abnormalities and inflammation. The morphology of the dilated vessels in rosacea may indicate an increase in the number and size of lymphatic vessels. We carried out a histological and an immunohistological study to quantify these abnormalities in rosacea and compared them with those seen in lupus erythematosus. MATERIALS AND METHODS: We reviewed all cases of rosacea analysed over a 4-year period. Ultimately, we only included 86 cases in which the diagnosis could be confirmed by a dermatologist based upon histopathological correlation and follow-up. All biopsies were reviewed for histopathological features, and 25 of these were compared with 25 facial biopsies in documented cases of lupus erythematosus, using standard staining followed by immunohistochemical analysis with anti-CD3, CD4, CD8 and CD20 (lymphocytic) antibodies, anti-CD68 (histiocytic) antibodies, anti-CD31 (endothelial cell) antibodies and anti-D2-40 (podoplanin, a marker for lymphatic endothelial cells) antibodies. RESULTS: In 88% of cases of rosacea, large superficial dermal vessels of geometrical or bizarre configuration were noted, and turgescent cells and dermal edema were frequently seen. Over 75% of cases involved Demodex, including erythemato-telangiectatic subtypes. The rosacea included a mean 15 vessels/mm(2), eight of which expressed D2-40; six were greater than 30µm in diameter (mean: 103µm; maximum: 400µm), with only two of these being D2-40+. The lupus erythematosus biopsies exhibited a mean 15 vessels/mm(2), nine of which expressed D2-40; four measured over 30µm in diameter (mean: 59µm; maximum: 100µm), of which two were D2-40+. The vessels measuring over 100µm were only seen in rosacea, and notable actinic elastosis was associated in 80% of these cases. No Demodex was seen in the lupus cases. The lymphocytic infiltration consisted mainly of CD4+ T cells in both groups, but was chiefly sub-epidermal in lupus, occasionally masking the small vessels of the superficial dermis. DISCUSSION: Rosacea is characterised by large, dilated, anfractuous capillaries, which are both larger and more numerous than in lupus, although there is no difference in dermal vascular density between the two diseases. Contrary to what their form may suggest, these dilated vessels are not lymphatic. D2-40+ vessels (lymphatic), which are flatter, are found in both lupus and rosacea. The association of large telangiectasias with actinic elastosis may indicate a causative role of exposure to UV radiation. These vessels likely exhibit increased permeability, resulting in dermal edema. Inflammation is consistently present, even in the early forms, strongly suggesting a dual inflammatory and vascular mechanism.

New concepts on the histogenesis of eccrine neoplasia from keratin expression in the normal eccrine gland, syringoma and poroma.

BACKGROUND: Peripheral and luminal layers of eccrine sweat gland ducts are self-renewing structures. Proliferation is restricted to the lowermost luminal layer, but randomly scattered in the peripheral layer. Each layer exhibits differential expression of keratins K5/K14 and K6/K16. Keratin K1 occurs only in peripheral cells and the novel keratin K77 is specific for luminal cells. OBJECTIVES: To investigate the expression of luminal (K77), peripheral (K1) and further discriminatory keratins in two eccrine sweat gland tumours: syringoma, thought to show differentiation towards luminal cells of intraepidermal sweat ducts and eccrine poroma, considered to arise from poroid cells, i.e. peripheral duct cells; and keratinocytes of the lower acrosyringium/sweat duct ridge differentiating towards cells of intradermal/intraepidermal duct segments. METHODS: Paraffin-embedded sections were examined by immunohistochemistry using several keratin, smooth muscle actin and Ki-67 antibodies. RESULTS: We confirmed the ductal nature of syringomas. Despite drastic morphological alterations in both layers, their keratin patterns remained almost undisturbed compared with normal ducts. In eccrine poroma epidermal keratins K5/K14 were ubiquitously expressed in all poroid cells. Cell islands deviating morphologically from poroid cells contained epidermal keratins K1/K10. K77 expression was limited to luminal cells of intact duct structures within the tumours. CONCLUSIONS: Syringomas are benign tumours of luminal cells of the lowermost intraglandular sweat duct. Poroid precursor cells of poromas do not comprise peripheral duct cells nor do poromas differentiate towards peripheral or luminal duct cells. Instead, poroid cells consist only of keratinocytes of the lowermost acrosyringium and the sweat duct ridge and poromas tend to differentiate towards the cells of the upper acrosyringium.

Expression of stromelysin 3 in basal cell carcinomas.

Stromelysin 3 is a member of the metalloproteinase family, which is expressed in various remodelling processes. The prognosis of breast cancers and squamous cell carcinomas is correlated to the level of expression of this protein. The purpose of the present work was to evaluate the expression of stromelysin 3 in the major types of basal cell carcinomas. We selected cases of primary tumours that were fully excised, without previous biopsy: 40 Pinkus tumors, 40 superficial, 40 nodular, 38 morpheiform basal cell carcinomas and 10 cases showing deep subcutaneous or muscular invasion. Immunohistochemistry was carried out using monoclonal anti-ST3 antibodies (MC Rio, IGBMC Strasbourg), and evaluated on a semi-quantitative scale from 0 to 3. Positively stained cells were restricted to the periphery of the epithelial cells, which, by contrast, never expressed stromelysin 3. The global rate of expression was 27% in Pinkus tumors, 65% in superficial, 72.5% in nodular, 87% in morpheiform and 100% in deeply invasive carcinomas. The rates of tumours showing the highest number of positively stained cells (class 2 or 3) were respectively 7.5%, 20%, 45%, 63% and 100%. This systematic study of stromelysin3 expression in basal cell carcinomas confirms that it is a marker of poor prognosis, because the rate of positive tumours was much higher in aggressive carcinomas. Moreover, the majority of tumours showing an intense expression (i.e. the highest number of positively stained cells in their stroma) were of the morpheiform and deeply invasive types, which are of poor prognosis. Altogether, the studies performed on cutaneous tumours are consistent with the theory of stromelysin 3 playing an active role in tumour progression.

A histologic and immunohistochemical study of chilblains.

BACKGROUND: The histopathologic diagnosis of chilblains is controversial and the histologic changes are often considered nonspecific, mainly because they are poorly documented. Although a dermal inflammation in chilblains has been noticed, the infiltrate has not yet been characterized. OBJECTIVE: Our purpose was to analyze microscopic and immunohistochemical findings in a large series of chilblains and to compare the results with those of lupus erythematosus (LE). METHODS: We included 36 cases of clinically typical chilblains of the hands, of which 17 were thoroughly investigated to rule out cryopathy or LE. Ten biopsy specimens of hand lesions from patients with proven LE were included as controls. All slides were analyzed by conventional microscopy and by immunohistochemistry with anti-CD3, anti-CD20, and anti-CD68 antibodies. RESULTS: The most characteristic finding in chilblains (47% of cases) was the association of edema and reticular dermis infiltrate that showed a perieccrine reinforcement. Such a combination of changes was not observed in LE. Epidermal changes in chilblains consisted mainly in necrotic keratinocytes in 52% of cases. The comparison of 17 idiopathic chilblains with LE showed significant differences in spongiosis (58% vs 0% respectively), vacuolation of basal layer (6% vs 60%), edema of the dermis (70% vs 20%), and deep perieccrine inflammation (76% vs 0%). Immunohistochemistry showed that the infiltrate was composed of a majority of T cells associated with macrophages and a few B lymphocytes. The same pattern was observed in both chilblains and LE. CONCLUSION: Our results show that a predominantly T-cell papillary and deep infiltrate with a perieccrine reinforcement, associated with dermal edema and necrotic keratinocytes, are the hallmarks of chilblains of the hands. These changes can help differentiate idiopathic perniosis from LE; immunohistochemistry is of no use in differentiation.

Expression of type I hair keratins in follicular tumours.

BACKGROUND: Hair keratins are specifically expressed in hair and nails. We previously demonstrated the expression of hair keratin basic 1 mRNA in pilomatrixomas. We recently developed a method for immunohistochemical staining of the group of acidic keratins, which have not yet been investigated in human tumours. OBJECTIVES: To study the expression of eight members of the type I hair keratin subfamily in pilomatrixomas and other skin tumours of follicular origin. METHODS: We performed immunohistochemistry on paraffin sections of formalin-fixed pilomatrixomas (40), trichoepitheliomas (10), trichoblastomas (10), desmoplastic trichoepitheliomas (10) and basal cell carcinomas (10), using antibodies against type I hair keratins hHa1, hHa2, hHa3-II, hHa4, hHa5, hHa6, hHa7 and hHa8 as well as cytokeratin CK17. RESULTS: While CK17 was found in almost all tumours investigated, hair keratins were exclusively expressed in pilomatrixomas. Their expression was restricted to areas of transitional cells, located between outer basophilic matricial cells and an inner zone of eosinophilic shadow cells. The most frequently and most strongly expressed hair keratins were hHa1, hHa2, hHa5 and hHa8, whereas hHa4 and hHa6 were only weakly expressed. No positive staining was observed with anti-hHa3-II and anti-hHa7 antibodies. Hair keratin expression in intermediate maturation stage pilomatrixomas resembled that of normal hair follicles, with early matricial and cuticular keratins hHa5 and hHa2 being expressed in lower transitional cells, followed by expression of early cortex keratins hHa1 and hHa8 in intermediate transitional cells and the late cortex keratins hHa4 and hHa6 in upper transitional cells. The latter were, however, seen only in a few intermediate maturation stage pilomatrixomas and were generally absent in late-stage pilomatrixomas. CONCLUSIONS: These changes in hair keratin expression patterns indicate that the maturation of pilomatrixomas towards large areas of shadow cells is associated with a gradual loss of differentiation-specific hair keratins. The complex hair keratin expression in pilomatrixomas is a further argument in favour of a hair matrix origin of this tumour.