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Macroscopic and histopathological alterations of foot pads of laying hens kept in small group housing systems and furnished cages.

1. Foot pad health was determined macroscopically and histologically in two trials with Lohmann Selected Leghorn (LSL, white layer strain) and Lohmann Brown (LB) laying hens kept in a small group housing system (40 and 60 hens) and two types of furnished cages (10 and 20 hens). 2. A total of 864 foot pads (648 LSL and 216 LB) were examined macroscopically and classified according to severity of pathological alterations; of these, 180 metatarsal pads and 180 toe pads were also examined histologically for hyperkeratosis, acanthosis, elongation of rete folds, development of secondary papillae, erosion, ulceration, cellular infiltration and bacterial colonisation of the epidermal surface. 3. As for the macroscopic examinations, pathological alterations of foot pads were found in 86.1% of the hens, while 57.4% of the birds examined showed mild hyperkeratosis. Macroscopically moderate hyperkeratosis and/or superficial lesions of the epithelium were detected in 21% of the laying hens examined. Severe hyperkeratosis and/or deep epithelial lesions and/or mild swelling of the foot pads were found in 5.9% of the hens, and very severe hyperkeratosis and/or deep and large epithelial lesions and/or moderate or high-grade swelling of foot pads were found in 1.9%. 4. The histopathological examinations showed that the macroscopically determined thickening of the epidermis was due not only to hyperkeratosis, but also often to acanthosis. In addition, perivascular infiltrations of lymphocytes were also detected. Furthermore, the degree of hyperkeratosis in metatarsal pads was shown to correlate with the other histopathological traits except for ulceration, and the degree of hyperkeratosis in toe pads was related to the development of secondary papillae and cellular infiltration with lymphocytes. 5. The results of the macroscopic and histological examinations showed that the use of perches and the grasping of wire floor may have resulted in a permanent increased mechanical compression load leading to proliferative hyperkeratosis.

Animals↗

Oral hairy leukoplakia: clinicopathologic features, pathogenesis, diagnosis, and clinical significance.

Oral hairy leukoplakia (OHL) is a lesion frequently, although not exclusively, observed in patients infected by human immunodeficiency viruses (HIV). OHL is clinically characterized by bilateral, often elevated, white patches of the lateral borders and dorsum of the tongue. Histologically, there is profound acanthosis, sometimes with koilocytic changes, and a lack of a notable inflammatory infiltrate. The koilocytic changes are due to intense replication of Epstein-Barr virus (EBV), while epithelial hyperplasia and acanthosis are likely to result from the combined action of the EBV-encoded proteins, latent membrane protein-1, and antiapoptotic BHRF1. How OHL is initiated and whether it develops after EBV reactivation from latency or superinfection remain unresolved; nevertheless, definitive diagnosis requires the demonstration of EBV replicating vegetatively in histological or cytological specimens. In patients with HIV infection, the development of OHL may herald severe HIV disease and the rapid onset of AIDS, but despite its title, OHL is not regarded as premalignant and is unlikely to give rise to oral squamous cell carcinoma.

HIV↗

Benign lichenoid keratosis.

The microscopic spectrum of benign lichenoid keratosis (BLK) was studied by examination of 30 examples. BLK consists of a segment of hyperplastic epidermis accompanied by a lymphoid infiltrate in the papillary dermis. Although termed "lichen planus-like," saw-tooth acanthosis predominated in only seven lesions, whereas irregular acanthosis was widespread in 23. The infiltrate had both a band-like (lichenoid) and perivascular arrangement, but a lichenoid appearance predominated in only half the specimens. Liquefaction of the basal layer was widespread, and hydropic change often involved the midepidermis. Mild cytologic atypicality was present in each case, but other features of actinic keratosis were lacking. Changes of senile lentigo were observed adjacent to 17 lesions. Partial involution was present in several cases. BLK often is confused clinically with a variety of other cutaneous tumors. Nevertheless, the diagnosis usually can be made on histologic grounds alone when the history indicates a solitary lesion.

Adult↗

Activating mutations of the tyrosine kinase receptor FGFR3 are associated with benign skin tumors in mice and humans.

Specific germline activating point mutations in the gene encoding the tyrosine kinase receptor FGFR3 (fibroblast growth factor receptor 3) result in autosomal dominant human skeletal dysplasias. The identification in multiple myeloma and in two epithelial cancers-bladder and cervical carcinomas-of somatic FGFR3 mutations identical to the germinal activating mutations found in skeletal dysplasias, together with functional studies, have suggested an oncogenic role for this receptor. Although acanthosis nigricans, a benign skin tumor, has been found in some syndromes associated with germinal activating mutations of FGFR3, the role of activated FGFR3 in the epidermis has never been investigated. Here, we targeted an activated receptor mutant (S249C FGFR3) to the basal cells of the epidermis of transgenic mice. Mice expressing the transgene developed benign epidermal tumors with no sign of malignancy. These skin lesions had features in common with acanthosis nigricans and other benign human skin tumors, including seborrheic keratosis, one of the most common benign epidermal tumors in humans. We therefore screened a series of 62 cases of seborrheic keratosis for FGFR3 mutations. A large proportion of these tumors (39%) harbored somatic activating FGFR3 mutations, identical to those associated with skeletal dysplasia syndromes and bladder and cervical neoplasms. Our findings directly implicate FGFR3 activation as a major cause of benign epidermal tumors in humans.

Animals↗

Lichen planus-like keratosis. A clinical and histological reexamination.

Lichen planus-like keratosis (LPLK) is a common skin lesion that has some morphologic features of lichen planus (LP) and lichenoid actinic keratosis (LAK). Although most authors consider LPLK to be a distinct lesion, surgical pathologists are often unfamiliar with it. We examined in detail the clinical and histologic features of LPLK in 100 consecutive cases. In our series, LPLK lesions occurred mostly in late-middle-aged individuals, on the trunk (64%) and extremities (31%) and predominantly in women (73%). Among the 14 histologic parameters that were studied, most LPLK had hyperkeratosis (81%) with hypergranulosis (77%), focal acanthosis (75%), and focal parakeratosis (59%). Solar elastosis was observed in 48% of the cases. Only a few cases had eosinophils (15%) or plasma cells (7%) in the inflammatory infiltrate. The adjacent skin was available for study in 71% of the specimens, and only 26.8% of the cases had an adjacent lesion, most frequently seborrheic keratosis (8.4%), solar lentigo (7%), and actinic keratosis (5.6%). According to our results, the most consistent features observed in LPLK are a lichenoid lymphocytic infiltrate with hyperkeratosis, hypergranulosis, focal acanthosis, and focal parakeratosis, without prominent atypia of keratinocytes.

Atrophy↗

Gastrointestinal manifestations of Cowden's disease. Report of four cases.

Four patients with an established diagnosis of Cowden's disease underwent barium meal study, upper gastrointestinal endoscopy, barium enema examination, and colonoscopy. In three, the esophagus was affected by small protrusions, which were diagnosed as glycogenic acanthosis. Numerous hyperplastic polyps were found in the stomach in three patients, and in one an inflammatory fibroid polyp was also detected. Either lymphangiectasia or lymphoid polyps were found in the duodenum in two patients. In all patients, the colon showed polyps that varied in histology and included adenoma, hamartomatous polyp, and ganglioneurofibroma. In addition, jejunal lymphangiomas were found in one of the three patients in whom the small intestine could be precisely evaluated. These findings suggest that the gastrointestinal involvement in Cowden's disease is characterized by various benign lesions, especially esophageal glycogenic acanthosis, numerous gastric hyperplastic polyps, and multiple hamartomatous polyps in the rectosigmoid colon. Detection of these gastrointestinal manifestations may lead to early diagnosis of this potentially malignant disease.

Adult↗

Benign lichenoid keratosis: a clinical and pathologic reappraisal of 1040 cases.

Benign lichenoid keratosis, otherwise known as lichen planus-like keratosis, is a common, cutaneous entity that is often confused with cutaneous malignancy. Few studies have examined the multiple clinical and pathologic guises of this entity, particularly within the context of clinical pathologic correlation or magnitude of this study. We examined the epidemiologic, clinical, and pathologic attributes of 1040 consecutive cases of benign lichenoid keratosis referred for pathologic examination at a busy laboratory over an entire year. Clinical parameters assessed included the age, anatomic location, gender, and multiplicity of the lesions. Pathologic attributes were assessed yielding discernment of five different subtypes that included a classic type, bullous type, atypical type with cytologically atypical lymphocytes, an early or interface type, and a late regressed or atrophic type. The results yielded an average age at presentation of 59.5 years with an age range of 36 to 87 years. The gender frequency was 76% female, 24% male. The trunk was the most common location (76%), followed by the extremities (33%) and head and neck (7%); 8% of patients presented with two lesions and less than 1% with three lesions prompting consideration of lichen planus. The classic, atypical, and bullous forms of the disease clinically presented with erythematous papule/plaque(s). The early or interface type showed erythematous to hyperpigmented brown macules and the regressed or atrophic type presented as violaceous papules or irregularly distributed macular pigmentation; 81% of the lesions showed the classic histology consisting of epidermal acanthosis with a band-like lichenoid lymphocytic infiltrate. Variable numbers of plasma cells, eosinophils, and neutrophils were identified as well as epidermal parakeratosis distinguishing these lesions from typical lichen planus. The bullous variant showed intraepidermal or subepidermal bullous cavities with a dense associated lymphocytic infiltrate and increased numbers of necrotic basilar layer keratinocytes. The atypical variant showed features of the classic type with scattered enlarged CD-3, CD-30 (+) lymphocytes possessing hyperchromatic, irregular nuclei. The early interface type showed single lymphocytes aligned along the dermoepidermal junction without epidermal acanthosis and adjacent lentigo. The regressed or atrophic variant showed epidermal atrophy with papillary dermal scarring, patchy lymphocytic infiltrates and melanin incontinence. The clinicopathologic spectrum of benign lichenoid keratosis is broad and encompasses several unrelated entities. An awareness of its expanded presentation is essential to avoid misdiagnosis and may serve as an important forerunner of pathogenic discernment.

Adult↗

Comparative study of pagetoid dyskeratosis between acrochordons and soft fibromas.

BACKGROUND: Pagetoid dyskeratosis (PD) is considered a casual finding. We can find it in some conditions, including acrochordons and soft fibromas. OBJECTIVE: (1) to compare the presence of PD in soft fibromas and acrochordons and (2) to compare PD positive fibromas and PD negative fibromas. MATERIALS AND METHODS: We reviewed all acrochordons and soft fibromas diagnosed in the General Hospital of Lanzarote, Spain, between January 2001 and December 2002. We assessed the presence of PD, size, acanthosis, basal pigmentation, and the presence of pseudohorn cysts. RESULTS: Three hundred sixty one acrochordons and 164 soft fibromas were included in this study. There were striking differences in the presence of PD, size, acanthosis, and basal pigmentation between both entities. PD positive fibromas predominated in axillas. There were no other differences between PD positive fibromas and PD negative fibromas. CONCLUSION: Although soft fibromas and acrochordons are actually fibroepithelial polyps, including the presence of PD, there are striking differences between them. Thus, both conditions have to be considered as different entities. PD could be related to friction and moisture. PD has to be distinguished from other conditions such as Paget's disease, pagetoid melanoma, koilocytes, clear cell papulosis, among others.

Axilla↗

Diagnostic utility of cell cycle and apoptosis regulatory proteins in verrucous squamous carcinoma.

A major problem in the diagnosis of verrucous squamous cell carcinoma is the lack of readily reproducible objective criteria for distinguishing this malignant lesion from reactive epithelial hyperplasia. Both lesions are characterized by thickened (well-differentiated) squamous epithelium without cellular atypia and subjacent stroma densely infiltrated by lymphocytes and plasma cells. This study was carried out to evaluate the use of cell cycle and apoptosis-related regulatory proteins in the diagnosis of verrucous carcinoma. The study materials consisted of representative formalin-fixed and paraffin-embedded tissue blocks from 19 cases of verrucous carcinoma, 18 classic squamous cell carcinoma, and 14 squamous epithelial hyperplasia (acanthosis). The immunohistochemical expression of the following of cell cycle and apoptosis-related regulatory proteins was evaluated using avidin-biotin complex detection technique: p16, p21, p53, Ki67, and retinoblastoma gene product (RBGP) (also known as retinoblastoma protein [pRb]). Expression of Ki67 was detected only in the single basal layer of the epithelium in all 14 cases of acanthosis. In verrucous carcinoma, Ki67 was detected in basal and suprabasal cells in the lower third of the neoplastic epithelium in 19 of 19 cases (100%). In neoplastic squamous epithelium with frankly invasive squamous cell carcinoma, Ki67 was diffusely expressed throughout the entire thickness of the epithelium as well as in the underlying invasive tumor nests. The pattern of p53 expression was similar to that of Ki67 in all the experimental groups, with a Pearson correlation coefficient of 0.98. In addition, immunohistochemical expression of p53 in the hyperplastic squamous epithelium was very weak, in contrast to the more intense immunoreactivity observed in verrucous carcinoma and classic squamous cell carcinoma. There was an overlapping in the expression of p16, p21, and RGBP in all the experimental groups, being present in more than half the thickness of the epithelium in 50% to 100% cases in each study group. We therefore conclude that the pattern of Ki67 and p53 expression in verrucous carcinoma is readily reproducible and distinctly different from that observed in epithelial hyperplasia and that seen in invasive squamous cell carcinoma. Thus Ki67, and p53 immunostains are reliable adjuncts that may be helpful in resolving diagnostic problems associated with verrucous carcinoma.

Adult↗

The in vivo effects of lymphokines on mitotic activity and keratinization in guinea pig epidermis.

Lymphokines may alter epidermal growth and differentiation contributing to changes such as acanthosis and hyperkeratosis. The main in vivo effects of lymphokines on epidermal mitotic activity were therefore investigated. Guinea pigs were injected intradermally with antigen-stimulated lymphocyte culture supernatants and a partially purified lymphokine preparation in phosphate buffered saline (PBS) 18, 24, 36 and 48 hr prior to biopsy. Control sites were injected with unstimulated supernatants and PBS respectively and the mitotic activity determined by use of a stathmokinetic agent. Both lymphokine injected areas and controls showed significantly increased mitotic indices compared to untreated skin which was apparent only at 24 hr. However mitotic activity in lymphokine lesions was significantly higher than in control lesions. There was no difference in the effect on mitotic activity between PBS and unstimulated culture supernatants. Lymphokine lesions at 24 hr also exhibited marked epidermal edema and acanthosis compared to minimal changes in controls. A variable patchy parakeratosis developed between 18 and 24 hr in areas injected with partially purified lymphokine but not in control sites or after injection with unpurified supernatants. The lymphokine-induced inflammatory infiltrate was mild and consisted mainly of neutrophils not differing significantly from that of the control lesions. This strongly suggests that lymphokines induce an alteration in epidermal kinetics and keratinization by a direct effect on keratinocytes and not indirectly via the dermal inflammatory infiltrate.

Animals↗

A case of seborrheic keratosis distributed along skin cleavage lines.

A 65-year-old woman with seborrheic keratosis following skin cleavage lines is reported. The mostly brownish-yellow lesions were located on the back. The round, oval, spindle, comet, and slightly raised papules varied from 1 mm to 2 cm in diameter. The distribution of lesions was unusual; they tended to follow skin cleavage lines on her lower back and waist. The arrangement of lesions was streamlined. The skin biopsy specimen revealed hyperkeratosis, acanthosis, and papillomatosis. The acanthosis was caused by proliferation of squamous and basaloid cells.

Aged↗

Photoageing: the role of UVB, solar-simulated UVB, visible and psoralen UVA radiation.

We have studied the morphological and histological effects of chronic exposure of two strains of haired mice (albino Balb/c and pigmented C3H-) to various types of radiation. UVB (280-320 nm) radiation from unfiltered sunlamp bulbs for 20 and 30 weeks produced marked epidermal acanthosis and dyskeratosis which was reversible in mice exposed for 20 weeks followed by a 20-week rest. In the dermis the elastic fibres were altered and in the pigmented mice these changes had almost completely reversed 29 weeks after cessation of exposure. Cellulose acetate-filtered sunlamp bulbs (greater than 289 nm) produced similar but less marked changes. Chronic exposure to UVA (320-400 nm) radiation produced minimal alterations in the dermis while the epidermis was normal. Visible (greater than 400 nm) radiation in large doses produced no degenerative changes. Methoxsalen/UVA radiation produced epidermal acanthosis, dermal sclerosis, and alteration of elastic fibres, which was prominent in both strains at 40 weeks. These findings suggest that the UVB component of sunlight is largely responsible for photoageing of the skin. Furthermore, chronic exposure to methoxsalen/UVA therapy is likely to potentiate solar-induced photoageing.

Aging↗

Objective measurement of three epidermal parameters in psoriasis vulgaris and in dermatopathology in general.

Three objective parameters which characterize the main features of the epidermis are described. One parameter relates to the mean thickness of the epidermis determined by a simple method. The second descriptive number is the ratio of the thickness of the strata corneum, lucidum and granulosum to the stratum malpighii. The third number relates to the degree of folding of the dermo-epidermal junction. The ratio of the mean thickness of abnormal to normal stratum corneum (for the same skin region) is suggested as an objective measure of hyperkeratosis; likewise, the ratio of abnormal to normal stratum malpighii is an objective measure of acanthosis. A single parameter can be measured against time to follow changes during the pathogenesis, treatment or remission of epidermal disease. As psoriasis undergoes progressive acanthosis, the geometry of the folding of the dermo-epidermal junction is such that cells of the stratum malpighii retain their close association with the cylindrical dermal papillae.

Adult↗

Confluent and reticulate papillomatosis (Gougerot-Carteaud syndrome): a minocycline-responsive dermatosis without evidence for yeast in pathogenesis. A study of 39 patients and a proposal of diagnostic criteria.

BACKGROUND: Confluent and reticulate papillomatosis (CRP) (Gougerot-Carteaud syndrome) is a disorder that has been characterized in only small cohorts of patients. OBJECTIVES: Better to characterize the clinical and pathological findings of the disorder. METHODS: We retrospectively reviewed the clinical presentation, response to treatment and histological findings of patients presenting to Mayo Clinic (Rochester, MN, U.S.A.) with CRP. RESULTS: The disorder was diagnosed in 39 patients between 1972 and 2003. Mean age at onset of the skin eruption was 15 years (range 8-32); 21 patients (54%) were male; most were white; most (33) presented for reasons of cosmesis; and eight described the rash as mildly pruritic. At presentation, the skin eruption had been present for a mean of 3.1 years (range 3 months-20 years) and had been recalcitrant to treatment, including antifungal treatment. Typical objective findings were scaling brown macules and patches and velvety papules and plaques, reticulated and papillomatous at least in part, involving the upper trunk, axillae and neck. The most frequent initial diagnostic impressions were tinea versicolor, acanthosis nigricans and CRP. Scales in 32 cases were examined with potassium hydroxide: eight (25%) showed hyphae, and 24 (75%) did not. Skin biopsy specimens from 21 patients showed variable degrees of hyperkeratosis, acanthosis and papillomatosis. Minocycline was prescribed for 22 patients, of whom 14 of 18 (78%) had complete clearing of the skin eruption and four (22%) a partial response. The skin eruptions recurred after stopping treatment in six patients. CONCLUSIONS: CRP occurs predominantly in young adults and teenagers, with cosmetically displeasing brown scaling patches and plaques affecting the neck, upper trunk and axillae. Frequently, the diagnosis is delayed and the disorder not recognized by physicians, including dermatologists. Clinically, the eruption is most often confused with tinea versicolor. Potassium hydroxide staining of the scale is negative in the majority of cases, implying that fungi are not involved in the pathogenesis of this condition, as has been previously proposed. It is important to recognize this disorder, because minocycline therapy is highly effective in most patients. Criteria for the diagnosis are proposed.

Adolescent↗

Early vulvar lichen sclerosus: a histopathological challenge.

Vulvar lichen sclerosus (LS), a lymphocyte-mediated chronic skin disease, begins with uncharacteristic symptoms and progresses undiagnosed to atrophy and destructive scarring. Some patients with longstanding advanced LS have an increased risk of vulvar carcinoma. Early LS is treatable, although not curable, if diagnosed early. Therefore, patients with persistent vulvar symptoms should be biopsied to establish the diagnosis. In contrast to advanced LS, the histological features in early LS are quite subtle and often more prominent in adnexal structures than in interfollicular skin. Adnexal structures show acanthosis, luminal hyperkeratosis and hypergranulosis with/without dystrophic hair and basement membrane thickening. The epidermis/mucosa shows mild irregular, occasionally psoriasiform acanthosis and focal basement membrane thickening. Early dermal changes are homogenized collagen and wide ectatic capillaries in dermal papillae immediately beneath the basement membrane. The lymphocytic infiltrate can be sparse or dense, lichenoid or interstitial with epidermal lymphocyte exocytosis and lymphocytic/lymphohistiocytic vasculitis. Dermal melanophages indicate preceding keratinocyte/melanocyte destruction. Biopsy specimens of early LS rarely display all features. Therefore, serial sections and periodic acid-Schiff reactions are necessary for their identification. Recognition and treatment of these early stages of LS may result in longstanding remission. Progression to atrophic stages with their associated morbidity and even to squamous cell carcinoma may be prevented.

Adult↗

Histologic and clinical findings in human scabies.

The epidermal histological findings in the primary scabetic lesion are hyperkeratosis, acanthosis, and spongiotic edema and vesiculation. The dermal changes consist of perivascular and diffuse cell infiltrates, mainly mononuclear cells, and sometimes eosinophilic granulocytes. The number of mast cells are slightly greater in primary scabetic lesions compared with secondary lesions and normal skin. Vasculitis is found in those cases showing tissue eosinophils, severe dermatitis, and many mites. A nodular lesion shows perivascular infiltrates mainly containing histiocytes, some with atypical and hyperchromatic nuclei and a few in mitosis, and some lymphocytes and cells with pyroninophilic cytoplasm. Secondary scabetic lesions show acanthosis and perivascular inflammatory cell infiltrates, mainly mononuclear cells, whereas clinically normal skin presents very slight perivascular and diffuse mononuclear cell infiltrates in half of the patients. Both the number of circulating eosinophilic granulocytes and serum IgE concentrations correlate with the severity of the skin reaction. Ten of 60 patients with scabies had markedly increased numbers of circulating eosinophilic granulocytes during scabies infestation. In most of the patients, however, the number of circulating eosinophils decreased after scabies treatment.

Biopsy↗

Histological changes in rabbits after application of medicaments and cosmetic bases.

A staged histological study of skin changes induced in rabbits by daily application of five bases used for topical medicaments and cosmetics, namely glycols, petrolatum, Modulan, Acetulan and Amerchol L 101, over periods of 100 days, is reported. Sections obtained every 10 days were examined for changes in the epithelium, in the character of the dermal infiltrate and in the superficial collagen fibers. Glycols showed no particular effects on the skin; petrolatum produced acanthosis and vacuolization in the epidermis, and mononuclear cell infiltration of the dermis but evident collagen changes. Lanolin derivatives produced acanthosis and vacuolization of the epidermis, with lymphomonouclear infiltration of the dermis and with dissociation of collagen; examination around the 30th day showed a tendency to basal layer disorganization by the infiltrate.

Animals↗

Role of histology in providing prognostic information in mycosis fungoides.

Many patients who present with patch and early plaque stage mycosis fungoides follow an indolent course and survive for many years following diagnosis. A certain subset of patients, however, have rapidly progressive disease leading to accelerated demise. We examined 21 histologic sections from initial biopsies taken from patients with stable disease and 26 from patients with rapidly progressive disease in order to evaluate the role of histology in predicting the disease course. Two or three authors examined each case and scored each of 24 histologic parameters using a previously described four-point scale with no knowledge of the patients' clinical courses. Interobserver agreement was quite high. The only histologic parameter that demonstrated statistical differences between the two groups of patients was degree of acanthosis. The degree of spongiosis, number of eosinophils, amount of hyperconvolution of dermal lymphocytes and density of the dermal infiltrate approached statistical significance but did not attain this level. All of these differences were quite small. No differences were seen for the other 19 parameters. Patients with rapidly progressive disease tended to have more acanthosis, a few more hyperconvoluted dermal lymphocytes, a slightly greater number of eosinophils and perhaps a slightly more dense dermal infiltrate than patients who had stable disease. However, as all of these changes were very slight, it appears unlikely that evaluation of any single biopsy specimen for the histologic parameters we studied is helpful in predicting the prognosis for a specific patient.

Biopsy↗