Reflectance confocal microscopy in the diagnosis of vesicobullous disorders: case series with pathologic and cytologic correlation and literature review.

BACKGROUND: Vesicobullous disorders are characterized by intraepidermal or subepidermal blistering resulting from different pathogenetic mechanisms. The diagnosis is generally based on clinical examination and semi-invasive/invasive procedures such as cytology and histopathology. In vivo reflectance confocal microscopy (RCM) is a non-invasive technique for real-time, en face imaging of the epidermis and upper dermis with high resolution close to conventional histopathology. PURPOSE: To evaluate RCM features of different vesicobullous diseases and correlate with cytologic and histopathologic examination. METHODS: Ten patients (6M/4F, age range: 9-81 years) affected by blistering diseases, such as herpes simplex, herpes zoster, Kaposi's varicelliform eruption, pemphigus vulgaris, Hailey-Hailey disease, bullous pemphigoid, and porphyria cutanea tarda were evaluated using a handheld RCM device. RESULTS: In our study, a clear correlation between RCM and Tzanck's test and/or histopathology was observed. RCM allowed in all cases an easy identification of the blister spaces and of the split levels, and in some cases specific features were detected, such as giant keratinocytes in herpes infections and acantholytic cells in pemphigus vulgaris and Hailey-Hailey disease. CONCLUSION: Reflectance confocal microscopy may support the clinical diagnosis of vesicobullous disorders and indicate to the physician the appropriate patient management and/or the need for further investigation.

Identification of granzyme B-expressing CD-8-positive T cells in lymphocytic inflammatory infiltrate in cutaneous lupus erythematosus and in dermatomyositis.

BACKGROUND: Lupus erythematosus (LE) and dermatomyositis (DM) are interface dermatitis, histologically characterized by formation of colloid bodies and a CD4+ CD8+ lymphocyte infiltrate. Colloid bodies are examples of intraepidermal apoptosis. Granzyme (Gr)B, synthesized by activated cytotoxic lymphocytes, is a serine protease able to prime apoptosis. GrB+ lymphocytes have been previously found in infiltrates in skin lesions from other types of interface dermatitis. AIM: To evaluate, on histological skin specimens from patients with LE and DM, GrB expression as a mediator of keratinocyte apoptosis in lymphocyte infiltrate. METHODS: In total, 22 patients with cutaneous LE [9 with discoid lupus erythematosus (DLE), 9 with subacute lupus erythematosus (SCLE) and 4 with systemic lupus erythematosus (SLE)] and 20 patients with DM were studied. Skin specimens underwent immunohistochemical staining with antibodies to CD3, CD4, CD8 and GrB. RESULTS: Immunohistochemical study with GrB was positive in 17 of the 22 patients with LE but only 2 of the 20 patients with DM. In LE, in systemic and subacute forms of LE, the median obtained was < 10 (+) whereas in the chronic forms, the median was 10-50% (++). Patients with DM were negative for GrB. CONCLUSIONS: In LE, a correlation between GrB+ lymphocyte and the presence of DLE form was found, but in DM, GrB is poorly expressed. GrB labels a subpopulation of effector cells involved in ongoing cytotoxic action and should be considered as a specific marker showing the extent of the direct local cytotoxic damage. GrB could play a role in the induction of skin apoptosis mechanisms in LE.

Interobserver reproducibility of histological features in cutaneous malignant melanoma.

AIMS: To assess the interobserver reproducibility of certain histological features proposed for the diagnosis of melanoma. METHODS: In a series of melanomas, 13 histological parameters were analysed: dimension > 6 mm, asymmetry, poor circumscription, irregular confluent nests, single melanocytes predominating, absence of maturation, suprabasal melanocytes, asymmetrical melanin, melanin in deep cells, cytological atypia, mitoses, dermal lymphocytic infiltrate, and necrosis. RESULTS: The agreement (reproducibility) between the nine observers was excellent (kappa > 0.75) for 10 of the 13 examined features (dimension > 6 mm, poor circumscription, irregular confluent nests, single melanocytes predominating, absence of maturation, suprabasal melanocytes, asymmetrical melanin, melanin in deep cells, mitoses, and necrosis). The agreement for asymmetry was very close to excellence (kappa = 0.74), and that for cytological atypia (kappa = 0.65) and dermal lymphocytic infiltrate (kappa = 0.47) was slightly lower, but in the fair to good agreement range. The kappa values obtained by comparison with the majority diagnosis were generally high (> or = 0.85); the mean value of kappa was lower (0.70) for only one parameter (dermal lymphocytic infiltrate). CONCLUSIONS: The parameters investigated showed an overall good reproducibility.

Histological features used in the diagnosis of melanoma are frequently found in benign melanocytic naevi.

AIMS: The histological features used in the diagnosis of melanoma may be present in benign naevi, but quantitative data are not available. The aim of this study was to establish the real prevalence of such features in naevi. METHODS: Ten dermatopathologists, from nine Italian institutions, studied a series of naevi. Eleven histological parameters currently used in melanoma diagnosis were analysed: asymmetry, poor circumscription, predominance of single melanocytes, irregular confluent nests, suprabasal melanocytes, hair follicle involvement, absence of maturation, cytological atypia, dermal lymphocytic infiltrate, mitoses, and necrosis. RESULTS: Ninety one naevi were examined: 22 junctional, 59 compound, and 10 intradermal. None of the studied parameters was seen in 22 of the benign naevi studied. One or more investigated features were found in 69 naevi. Poor circumscription was found in 49 cases, single melanocytic predominating in 42, asymmetry in 41, irregular confluent nests in 16, cytological atypia in 14, suprabasal melanocytes in seven, and hair follicle involvement in seven; absence of maturation, mitoses and necrosis were not found. CONCLUSIONS: The histological features used for the histological diagnosis of melanoma are often present in benign melanocytic naevi. This suggests a critical, non-mechanical use of them in melanoma diagnosis.

Melanocytic nevi of the breast: a histologic case-control study.

BACKGROUND: Melanocytic nevi in the genital, acral, and flexural sites often display clinical and histologic features that may simulate melanoma. We verified whether this is the case also for nevi of the breast. METHODS: Eleven dermatopathologists, from nine Italian Institutions, collected the specimens of melanocytic lesions from the breast and other body sites, excluding the acral, genital, and flexural areas, as controls. Cases and controls were matched for sex and age. All nevi were observed 'blindly' and simultaneously by all participants. For each lesion, 10 histological parameters were analyzed: asymmetry, absence of lateral demarcation of melanocytes, lentiginous proliferation, nested and dyshesive pattern, intraepidermal melanocytes above the basal layer, involvement of the hair follicle, absence of maturation of dermal melanocytes, melanocytic atypia, fibroplasia of the papillary dermis, and lymphocytic dermal infiltrate. Each parameter was scored 2 when present and 1 when absent or not valuable. A total score was calculated for each lesion. Results were statistically analyzed by the chi-square test and the Mann-Whitney U-test. RESULTS: One hundred and one nevi came from the breast area and 97 from elsewhere. Breast nevi exhibited significantly more atypical features than nevi from other sites. In particular, breast nevi with intraepidermal melanocytes, melanocytic atypia, and dermal fibroplasia were significantly more numerous. We did not find any sexual difference. CONCLUSIONS: To avoid undue concerns, dermatopathologists should be aware that melanocytic nevi of the breast may show a high degree of atypical features.

Reproducibility of histopathologic diagnosis and classification of non-melanocytic skin cancer: a panel exercise in the framework of the multicenter southern European study HELIOS.

AIMS AND BACKGROUND: The reproducibility of histologic diagnoses, and in particular of the distinction between basal and squamous cell forms, has been evaluated in the framework of a multicenter case-control study (in Italy, France, Spain and Switzerland) aimed to assess the causes of non-melanocytic skin cancers. METHODS: A panel composed of 10 pathologists from the collaborating centers was appointed. A total of 1,774 slides of routine diagnoses were blindly reviewed by a second panelist; discordant diagnoses underwent a third examination. Controversial and interesting cases were discussed during general sessions. RESULTS: The results showed a high degree of concordance (99.5%), with a Cohen's kappa of 0.85 (95% CI, 0.77-0.94) in the assessment of malignancy of lesions. The concordance in the distinction between large morphologic groups, basal cell carcinoma and squamous cell carcinoma was also high (Cohen's kappa = 0.85; 95% CI, 0.82-0.89). The assessment of histologic subtypes, degree of invasion and differentiation showed a lower degree of concordance, presumably as a consequence of a weaker consistency in the relevant classifications. CONCLUSIONS: The reproducibility study has therefore validated the epidemiologic study and in particular allowed to correct some misclassifications that could have lessened the analysis of the case-control study. In general, because of its characteristics (number of pathologists and variety of their origins, the large number of cases examined, blind examination of histologic slides), the conclusions of the study may show a certain degree of generalization, at least with regard to the countries represented. Routine histologic diagnoses of cutaneous carcinoma showed a high degree of reliability with reference to the assessment of malignancy and the distinction between basal and squamous cell carcinoma morphotypes.

Immature myeloid precursors in chronic neutrophilic dermatosis associated with myelodysplastic syndrome.

Sweet syndrome (SS) associated with myeloproliferative disorders has been considered an inflammatory process mediated by neutrophils in which immunologic mechanisms are operative. The authors report the case of a 68-year-old man suffering from a myelodysplastic syndrome, who presented with a relapsing skin eruption resembling SS. Histopathologically, the skin infiltrates showed prominent neutrophilic features masking the underlying malignant process. Extensive immunophenotypic studies of skin revealed the presence of a few immature myeloid cells intermingled with an overwhelming infiltrate of neutrophils. The atypical cells in the skin had a phenotype identical to that of leukemic cells in the peripheral blood and bone marrow. Whether or not immature myeloid cell precursors constitute a specific infiltrate of leukemia cutis or are a result of recruitment of circulating leukemic cells to this area of inflammation is discussed.

Angioendotheliomatosis in a woman with rheumatoid arthritis.

Reactive angioendotheliomatosis (RA) is a rare self-limited skin condition characterized histopathologically by a proliferation of endothelial cells within vascular lumina, usually as a result of different stimuli such as systemic infections, cryoproteinemias, monoclonal gammopathies, allergic conditions, severe peripheral vascular atherosclerotic disease, and iatrogenic arteriovenous fistulas. We report on a 67-year-old woman with a 20-year history of seropositive rheumatoid arthritis who presented with violaceous swelling of her left forearm. A skin biopsy revealed the histopathologic finding of RA with focal glomeruloid features and deposition of periodic acid-Schiff-positive material. In this systemic disorder, cutaneous manifestations may occur secondary to an immune complex-mediated vasculitic mechanism.

The clinicopathologic spectrum of rhinophyma.

We report the results of a clinicopathologic study of 17 patients with rhinophyma in different stages of evolution, with particular attention paid to the severe form of this disease. On the basis of clinical features, we identified 2 groups of patients: the first group (12/17 patients) included patients with the common form of rhinophyma, whereas the second one (5/17 patients) included patients with the severe form of the disease. There was no link between the clinical aspect and the duration of the disease. Microscopic examination of specimens obtained from the classic type of rhinophyma substantially showed the histopathologic features of fully developed rosacea, except for the presence of prominent sebaceous hyperplasia. The second group showed a very different histologic pattern displaying marked dermal thickness, absence of folliculosebaceous structures, sclerotic collagen bundles with large amounts of mucin, and spreading telangiectasia. The inflammatory infiltrate was inconspicuous, with numerous interstitial spindle and bizarre cells. Most of the interstitial cells were reactive to factor XIIIa. The severe form of rhinophyma shares many histologic characteristics with elephantiasis caused by chronic lymphedema.

Dermatofibroma with granular cells: a report of two cases.

We describe two examples of an unusual variant of dermatofibroma (DF) in which areas of granular cells were a prominent feature. The diagnosis of DF was confirmed by immunohistochemistry and by ultrastructural studies. Granular cell changes can be observed in numerous benign and malignant cutaneous tumors of different cellular lineage. Cellular granularity is a nonspecific phenomenon characterized by intracytoplasmic accumulation of lysosomes and may cause diagnostic difficulties. Traumatic factors may be involved in the pathogenesis of cellular granularity.

Interstitial granulomatous dermatitis with plaques.

We report on the clinical and histopathologic findings of four patients who had asymptomatic, erythematous to violaceous plaques symmetrically distributed on the upper aspect of the thighs, lateral chest, and in two cases also on the abdomen and flexor surface of the elbows. All of the patients were women; two of them had arthritis, which in one case was associated with an autoimmune disorder, and another had autoimmune thyroiditis. Histopathologically, all cases showed similar changes consisting of an interstitial granulomatous dermatitis involving mostly the lower reticular dermis. Histiocytes were the predominant cellular component, arranged interstitially and in small palisades around foci of degenerated collagen bundles in concert with large numbers of neutrophils and eosinophils. Interstitial granulomatous dermatitis can present different clinical expressions, including linear cords, papules, and, as in our cases, plaques. This peculiar histopathologic pattern falls into the spectrum of cutaneous extravascular necrotizing granuloma, a condition that is often associated with systemic autoimmune disease.

[Estimate of the proportion of skin tumors attributable to sun exposure in 3 Italian populations]. / Stima della proporzione di tumori cutanei attribuibili all'esposizione solare in tre popolazioni Italiane.

Translation of recommendations on skin cancer prevention formulated by many national and international institutions into efficient steps requires measuring the potential impact in terms of preventable cases. This study analyses the proportion of skin cancers attributable to sun exposure in Turin, Trento and Ragusa. Estimates have been reached by applying the risk models calculated from the case-control study on melanoma in Turin and the Helios multi-centric study on skin carcinomas. The proportion of cases attributable to sun exposure has been subsequently calculated by correcting for the different proportion of skin characteristics among the populations taken into consideration. Attributable risks so calculated show medium to high values for melanoma in Turin (38%) and Trento (29%), while values are lower in Ragusa (17%). As for basal-cell carcinoma, attributable risk values are slightly inferior to those of melanoma. The risk of squamous-cell carcinoma attributable to sun exposure during outdoor work is the highest in Ragusa, with a value of 25%. Taking an annual incidence rate for melanoma of 9 cases per 100,000 inhabitants, and a preventive intervention with 50% of effectiveness, preventable cases should be 2 cases per 100,000 each year. This figure compared with 8 preventable cases of cervix cancer, in a similar population suggests an extremely cautious attitude in taking on programmes aiming to change life styles.

Multinucleate cell angiohistiocytoma: a report of two cases.

We report the clinical, histological and immunological features of two cases of multinucleate cell angiohistiocytoma (MCAH) in women of 32 and 53 years of age, respectively. Clinically, MCAH occurs mostly in middle-aged women and consists of crops of reddish-purple, dome-shaped papules especially on the limbs. Histologically, the reticular dermis presents an increased number of small vascular channels with plump endothelial cells embedded in a fibrohistiocitic stroma with numerous bizarre multinucleate cells. Bizarre multinucleated cells are not specific to MCAH; they can be observed in numerous other cutaneous conditions. However, MCAH presents quite distinctive clinico-pathological findings and may be easily differentiated from other cutaneous disorders.

Parallel risk assessment of melanoma and basal cell carcinoma: skin characteristics and sun exposure.

In this study we compared the strength of the association of constitutional factors and sun exposure with cutaneous malignant melanoma (CMM) and basal cell carcinoma (BCC). We analysed 260 incident cases of CMM, 425 incident cases of BCC and two sets of population controls from previous case-control studies conducted in Turin, Italy. Simultaneous comparison was accomplished by comparing separate simple logistic and polytomous logistic regressions. Tendency to sunburn was shown to be the most important risk indicator for both types of tumours, being associated with a two- to three-fold increase in risk for CMM and a two-fold increase in risk for BCC. Intermittent and intense sun exposure, as during beach holidays, increased the risk of both CMM and BCC, while prolonged exposure to sun, as during outdoor occupations, was not associated with CMM or BCC. The increase in risk during beach holidays occurred mainly during childhood for CMM cases, while for BCC cases it also continued during adulthood. Analysis of the independent effect of risk factors confirmed the role of skin phenotype (eye colour odds ratio [OR] = 1.6, tendency to sunburn OR = 2.1) and intermittent sun exposure (sunburns in childhood OR = 3.8, sun exposure during beach holidays OR = 1.2) in CMM. Risk of CMM showed a significant increase when sun exposure exceeded the threshold of about 3500 h during beach holidays cumulated in a lifetime. In contrast, the role of skin phenotype in BCC is less strong, but cumulated hours of sun exposure during beach holidays in a lifetime showed a constant risk rise with an early plateau at a low exposure level.

Psoriatic erythroderma: a histopathologic study of forty-five patients.

BACKGROUND: There are conflicting opinions about the diagnostic value of skin biopsy in erythrodermic psoriasis. OBJECTIVE: The purpose of the present study was to establish the specificity of the histopathologic changes of psoriatic erythroderma. METHODS: We reviewed 52 skin biopsies from 45 erythrodermic patients having a final diagnosis of psoriasis on the basis of combined clinical and laboratory data, in addition to response to therapy and follow-up. In 5 patients, erythroderma was the presenting sign of psoriasis. A control group of nonpsoriatic erythrodermic patients was also included in the study. RESULTS: Among the group of patients with a discharge diagnosis of psoriatic erythroderma, the histopathologic changes were specific for psoriasis in 40 cases (88%). The changes of early macular and squamous lesions of psoriasis were more often found in the biopsy specimens of our series than those of fully developed or late lesions of psoriasis. They included mainly slight epidermal hyperplasia, focal disappearance of the granular layer, mounds of parakeratosis and extravasated erythrocytes within edematous dermal papillae associated with perivascular and interstitial infiltration of lymphocytes and histiocytes. CONCLUSION: When features of early lesions of psoriasis are found during the evaluation of a biopsy specimen from a patient with a clinically nonspecific erythroderma, the dermatopathologist should be aware that this patient could have psoriasis and a renewed anamnesis and a close follow-up should be made.

Diffuse and bilateral lichen striatus.

A 5-year-old girl had a papulo-squamous dermatosis arranged in a Blaschko line pattern of 1 month's duration. The skin lesions were asymmetrically distributed bilaterally on the face, neck, trunk, and limbs. Histologically there was a lichenoid infiltrate with foci of spongiosis. The dermatosis cleared spontaneously with hypopigmentation 16 months later. Lichen striatus usually occurs in a solitary and unilateral fashion. Its diffuse and bilateral distribution is an uncommon presentation.

Vulvodynia and HIV: causal or casual association?

BACKGROUND: No study exists on HIV and vulvodynia. OBJECTIVE: To evaluate vulvodynia in HIV infected women and its possible association with HIV. DESIGN: Cross sectional study. SETTING: Department of Medical and Surgical Sciences, Section of Infectious Diseases, University of Turin. METHODS: 235 HIV positive and 272 HIV negative women were studied for vulvar pain between June 1995 and January 1997. Diagnosis of vulvodynia was based on clinical history, dermatological and vulvovaginal examination, and bacteriology. Colposcopy and vulvar biopsy were performed and psychometric examination was done. RESULTS: Vulvodynia was diagnosed in five women with HIV and in one uninfected woman (odds ratio = 2.5; 95% confidence interval: 0.1-62.6). High neuroticism scores were observed in women with history of vulvar pain, the highest in HIV infected vulvodynia patients (p = 0.000). CONCLUSIONS: Confirming the association of gynaecological pain with neurotic personality, our study suggests causal link between HIV and vulvodynia.