The lectins Peanut agglutinin (PNA), Canavalia ensiformis (Con A), Ulex europaeusl (UEAl), Dolichos biflorus (DBA), Triticum vulgaris (WGA) were studied in a series of 36 meningiomas (16 meningotheliomatous-including 3 recurrences, 7 transitional, 4 angiomatous, 2 ((hemangiopericytic~, 3 papillary-including 1 recurrence, 4 anaplastic-including 3 recurrences. PNA binds to all cases of meningotheliomatous, transitional, papillary and anaplastic meningiomas (including recurrent cases) but the staining is more intense in tumor cells of anaplastic and papillary type. A semiquantitative study showed differences of PNAreactivity in the different subtypes of meningiomas. In meningotheliomatous meningiomas PNA-positivity was encountered in numerous neoplastic cells (50%), whereas papillary and anaplastic subtypes expressed strong cytoplasmic staining of few tumor cells (C 5%). Con A shows the same pattern of reactivity described for PNA, but more weakly. Our results suggest that PNA is a marker of differentiation in meningiomas rather than malignant transformation and can have prognostic relevance.

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.

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 (>= 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.

A 40-year-old man under treatment for hypertension for almost 1 year with an angiotensin-converting enzyme (ACE) inhibitor (enalapril) presented with recurrent chronic dermatitis of the face and trunk for several months. Physical examination revealed 2 nonpruriginous, erythematous, arciform plaques located in the thoracomammary region (fig. 1). A less infiltrated oval plaque was located in the left preauricular region. The lesions resolved after interruption of enalapril and application of topical steroids. A relapse was observed in the same region after reintroduction of the drug. Discontinuation of the treatment with enalapril was followed again by resolution of the lesions. The subsequent administration of valsartan, an angiotensin II receptor antagonist similar to enalapril, caused the appearance of similar lesions within few weeks. We performed a 5-mm punch biopsy from one of the chest lesions. Histology showed micronodular inflammatory infiltrates scattered in the dermis around the small vessels and the adnexal structures, with a pattern typical of the so-called lymphocytic infiltration of Jessner-Kanof (fig. 2). The cells were T lymphocytes, mainly CD8 positive, and histiocytes scattered and in small clusters, with sporadic fragmentation of the collagen fibers. The direct immunofluorescence and the iron staining for mucin were negative. The ACE inhibitor therapy was discontinued, and the hypertension was treated with an ·-blocker medication. Complete resolution of the dermatitis was observed within a couple of weeks, and at 6 months of follow-up no signs of relapse were observed. A 48and 72-hour patch test reading with enalapril did not show any positive reaction. This clinical case is an example of druginduced cutaneous reaction (specifically by ACE inhibitors) with a histological pattern resembling lymphocytic infiltration of JessnerKanof. There are several reports in the literature regarding skin disorders following treatment with ACE inhibitor drugs, especially enalapril. In the cases reported, the clinical diagnoses were granuloma annu-

Summary Four cases of human “equine” melanoma are presented. Two had poor prognosis, evidenced by the presence of metastases, and one of these with a rapidly fatal outcome. Human “equine” melanoma is characterized by an expansive, compact, heavily pigmented, dermal melanocytic proliferation without epidermal involvement. The mitotic index is always low, while minute foci of necrosis are present. The differential diagnosis is discussed, outlining the overlapping of the histological features with those of the malignant blu nevus. The only difference is the possible presence in the latter of areas characteristic of either common blu nevus or cellular blu nevus. With regards to the histogenesis of human “equine” melanoma we found no elements to support a follicular sheath origin and we propose a possible perineurial origin.

Four cases of human "equine" melanoma are presented. Two had poor prognosis, evidenced by the presence of metastases, and one of these with a rapidly fatal outcome. Human "equine" melanoma is characterized by an expansive, compact, heavily pigmented, dermal melanocytic proliferation without epidermal involvement. The mitotic index is always low, while minute foci of necrosis are present. The differential diagnosis is discussed, outlining the overlapping of the histological features with those of the malignant blu nevus. The only difference is the possible presence in the latter of areas characteristic of either common blu nevus or cellular blu nevus. With regards to the histogenesis of human "equine" melanoma we found no elements to support a follicular sheath origin and we propose a possible perineurial origin.

A 67‐year‐old housewife was referred to us for a papulonodular keratotic lesion on the left side of the left eyebrow (Fig. 1). The lesion had started to develop 6 months earlier and had gradually reached a size of 2 cm in diameter. It was firm, nonitching, and painless on pressure.Papulokeratotic lesion on the left eyebrowimageHistologic examination of a punch biopsy obtained from the reddish edge of the nodule showed a jagged epidermal profile with areas of hyperplasia alternating with areas in which the epidermis was thin. The epidermis showed multifocal acanthosis, diffuse hypergranulosis, and hyperorthokeratosis; only focal hyperparakeratosis was present. The basal layer showed spotty areas of liquefaction degeneration, with superimposed lymphocytic infiltrate, and exocytoses that indented the profile of the dermo‐epidermal junction. Focally, some eosinophilic bodies were present. Keratinocytes with hyperchromatic nuclei were also present in the lower layer of the epidermis (Fig. 2).Histologic examination showing epidermis with acanthosis, hypergranulosis, and hyperorthokeratosis; keratinocytes with hyperchromatic nuclei can also be seen in the lower layer. The papillary dermis shows a band‐like lymphocytic infiltrate (original magnification, × 10)imageThe papillary dermis showed a mostly band‐like infiltrate consisting predominantly of lymphocytes, a few melanin‐poor histiocytes, and very rare eosinophils; telangiectases and solar elastosis were also present.

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.

To assess if the quantity of silver-stained nucleolar organizer region (AgNOR) proteins predicts the behavior of actinic keratosis (AK), we performed a standardized AgNOR analysis on 51 cases of AK; in addition, 10 cases of squamous cell (SCC) and 10 cases of basal cell (BCC) carcinomas and 10 normal skin samples were also studied. AgNOR analysis was performed on formalin-fixed and paraffin-embedded sections according to the guidelines of the Committee on AgNOR Quantification (1995), evaluating the mean area (microm(2)) of AgNORs per nucleus (NORA). A highly significant P value (< 0.001) was found in the comparison among NORA values of normal skin (1.869 microm(2); SD + 0.332), AK (3.988 microm(2); SD + 0.914), BCC (3.044 microm(2); SD + 0.254), and SCC (5.286 microm(2); SD + 0.920). In AK, a progressive increase of mean NORA values was observed moving from Stage I (3.161 microm(2); SD + 0.600) to Stage II (3.455 microm(2); SD + 0.562), Stage III (4.360 microm(2); SD + 0.295), and Stage IV (5.168 microm(2); SD + 0.694); highly significant differences (P < 0.001) were noted when Stages I or II were compared with Stage III or Stage IV or between these latter stages. The AgNOR quantity may identify AKs with high proliferative activity and increased tendency to develop into invasive SCC.

Because the CD30 ligand (CD30L)/CD30 receptor (CD30) system is expressed in certain malignancies, but has not been studied in thyroid nodules, we investigated its immunohistochemical expression in 6 normal thyroids (NT) and 131 thyroid nodules: 28 colloid nodules (CN), 45 adenomas (15 oncocytic [OA], 30 follicular [FA]) and 58 carcinomas (15 follicular [FTC], 1 insular [ITC], 6 anaplastic [ATC], 30 papillary [PTC], and 6 medullary [MTC]). NT and CN expressed neither CD30L nor CD30 (CD30L(-)/CD30(-)). Forty percent of OA and 20% of FA showed epithelial coexpression of CD30L and CD30, and interstitial expression of CD30L, which was also observed in the surrounding normal tissue. Within malignancies, epithelial coexpression of CD30L and CD30 was observed in 7% of FTC, 33% of ATC, 67% of PTC, and 67% of MTC. Only PTC and MTC showed epithelial expression of CD30L in the perinodular tissue with similar frequency (80% PTC, 75% MTC). PTC and MTC had the highest proportion of CD30L(+) or CD30(+) cells, and together with OA, a thus far unreported nuclear location of CD30L. In PTC, the proportion of CD30L(+) cells and the prevalence of nuclear location of CD30L correlated inversely and directly, respectively, with aggressiveness. Ln conclusion, CD30L/CD30 signaling is activated only past the colloid nodule stage, most frequently in an autocrine fashion.

Abstract: We describe an 8‐year‐old boy with Rubinstein–Taybi syndrome, a multiple congenital anomaly/mental retardation syndrome characterized by broad thumbs and great toes, peculiar facies, and mental retardation caused by mutations in the transcriptional coactivator CREB binding protein (CBP). He had on his right side yellowish papular lesions organized in narrow bands according to Blaschko lines, later confirmed by histology as an epidermal nevus. Epidermal nevus syndrome has been ruled out because the patient failed to meet the criteria for inclusion under this designation. This association may be coincidental.

Papillon-Lefèvre syndrome is characterized by the association of palmoplantar hyperkeratosis, severe periodontitis, and early loss of deciduous and permanent teeth. We report two patients from the same family, aged 21 and 30 years, who were unaware of their pathology; one was successfully treated with etretinate.

Sir, In 1951, Favre & Racouchot described a disease characterized by nodular elastosis with cysts and comedones (1). The disease is localized on the lateral canthi of the eyes, temples, cheeks, nucha, retro-auricular regions and, more rarely, on the chin and nose. The skin is wrinkled and intensely dark over the lesions. The disease develops gradually in elderly males and is frequently associated with cutis rhomboidalis nuchae and disorders due to sun exposure.

Papillary thyroid cancer (PTC), but neither the follicular nor the anaplastic histotype [follicular thyroid cancer (FTC), anaplastic thyroid cancer (ATC)], overexpresses simultaneously the protooncogene HGF (hepatocyte growth factor) and its receptor HGF-R (or c-met). Because 1) HGF and c-met map to chromosome 7q21 and 7q31, respectively, 2) FTC loses genetic material at multiple loci with a frequency much higher than PTC, and 3) loss of heterozygosity (LOH) on 7q has been previously found in various tumors, we tested the hypothesis that both FTC and ATC, but not PTC, could harbor LOH in segments of 7q encompassing the loci for HGF and c-met. We screened 6 normal thyroids, 10 colloid nodules, 10 follicular hyperplasias, 10 oncocytic adenomas, 10 follicular adenomas (FA), 10 FTC, 6 ATC, 12 PTC using two microsatellite markers for HGF, and two for c-met. LOH for all 4 markers was found in 100% of FTC, 100% of ATC, and (for only 1 or 2 markers) in 10-29% of FA. This is the first demonstration of an LOH that separates both FTC and ATC from PTC, in the best possible manner: 100% vs. 0%. Clearly, each of the two segments we have probed contains at least one tumor suppressor gene, whose inactivation is crucial for the establishment of the FTC (and ATC) phenotype. This loss of genetic material explains why FTC and ATC, but not PTC, fail to express both HGF and c-met. Our findings may also have immediate diagnostic application, in the context of assisting pathologists in the often difficult task of distinguishing FA from FTC.

We report a 9-year-old boy affected by LEOPARD syndrome, who also had ichthyosis, axillary freckling, two café au lait spots, and one neurofibroma. The diagnosis of LEOPARD syndrome has been made on clinical grounds, whereas the ichthyosis and neurofibroma have been histologically confirmed. The analogies between LEOPARD syndrome and neurofibromatosis have been discussed. Finally, we maintain this case is an example of the multiple lentigines syndrome/LEOPARD syndrome spectrum.