Panniculitis with vasculitis.

Panniculitides encompass a great number of different entities; however, once a vasculitis has been detected histopathologically within the subcutaneous tissue, the differential diagnosis is mainly restricted to polyarteritis (panarteritis) nodosa (PAN), nodular vasculitis (NV), and Bazin's erythema induratum (EI). Patients with PAN may have the disease confined to the skin, but must be followed over a long period because many of them develop late systemic disease. The NV/EI group represents by far the most common type of lobular panniculitis with vasculitis; we prefer keeping the distinction between the two entities by underlining the equation NV positive tuberculin skin test = EI. Other lobular panniculitides with vasculitis are exceedingly rare and set in a systemic background which can be infectious (lepromatous leprosy panniculitides) or autoimmune/dysreactive (neutrophilic lobular panniculitis in rheumatoid arthritis, lobular panniculitis in inflammatory bowel disease).

Granulocyte/macrophage colony-stimulating factor treatment of human chronic ulcers promotes angiogenesis associated with de novo vascular endothelial growth factor transcription in the ulcer bed.

Summary Background Granulocyte/macrophage colony-stimulating factor (GM-CSF), a cytokine with pleiotropic functions, has been successfully employed in the treatment of chronic skin ulcers. The biological effects underlying GM-CSF action in impaired wound healing have been only partly clarified. Objectives To investigate the effects of GM-CSF treatment of chronic venous ulcers on lesion vascularization and on the local synthesis of the angiogenic factors vascular endothelial growth factor (VEGF) and placenta growth factor (PlGF). Methods Patients with nonhealing venous leg ulcers were treated with intradermal injection of recombinant human GM-CSF, and biopsies were taken at the ulcer margin before and 5 days after administration. Wound vascularization was analysed by immunohistochemistry using antiplatelet endothelial cell adhesion molecule-1/CD31 and anti-alpha-smooth muscle actin antibodies. VEGF and PlGF transcription was assessed by in situ hybridization. To identify the cell populations transcribing VEGF within the ulcer bed, the VEGF hybridization signal was correlated with the immunostaining for different cell type markers on serial sections. Direct induction of VEGF transcription by GM-CSF was investigated in GM-CSF-treated cultured macrophages and keratinocytes. Results Blood vessel density was significantly increased in the ulcer bed following GM-CSF treatment. VEGF transcripts were localized in keratinocytes at the ulcer margin both before and after GM-CSF treatment, whereas a VEGF hybridization signal was evident within the ulcer bed only following administration. PlGF mRNA was barely detectable in keratinocytes at the ulcer margin and was not visibly increased after treatment. Unlike VEGF, a specific PlGF hybridization signal could not be detected in cells within the ulcer following GM-CSF administration. Monocytes/macrophages were the main cell population transcribing VEGF after GM-CSF treatment. In vitro analysis demonstrated that VEGF transcription can be directly stimulated by GM-CSF in a differentiated monocytic cell line, but not in keratinocytes. Conclusions Our data show that increased vascularization is associated with GM-CSF treatment of chronic venous ulcers and indicate that inflammatory cell-derived VEGF may act as an angiogenic mediator of the healing effect of GM-CSF in chronic ulcers.

Persistent unilateral orbital and eyelid oedema as a manifestation of Melkersson-Rosenthal syndrome.

Melkersson-Rosenthal syndrome (MRS) is a complex neuromucocutaneous disorder characterized by localized orofacial oedema and cranial nerve dysfunction, frequently associated with minor signs, including furrowed tongue. Complete forms are rare whereas mono- and oligosymptomatic variants are more common. A 71-year-old man presented with a 2-year history of relapsing and progressively persistent oedema of the right eyelids and periorbital region. A fissured tongue and telangiectatic rosacea had been present since the age of 50 and 60 years, respectively. The patient was also affected by essential hypertension and diabetes mellitus. A skin biopsy showed a marked upper dermal oedema, and small epithelioid cell granulomas arranged in perivascular and perilymphatic location. Collections of small epithelioid cells were occasionally observed within lymphatic spaces. No acid-fast bacteria, fungi or foreign bodies were detected. Intralesional corticosteroids induced transient improvement, whereas minocycline, clofazimine and dapsone have been ineffective. MRS may present with unilateral eyelid and periorbital swelling. Differential diagnoses of such cases may include a variety of cutaneous, ophthalmic and systemic diseases.

[Successful treatment of Norwegian scabies with ivermectin in a patient with recessive dystrophic epidermolysis bullosa]. / Scabbia norvegese ed epidermolisi bollosa distrofica recessiva: efficacia della terapia con ivermectina.

A 14 year-old female born from consanguineous healthy parents was admitted to our institute for the presence of a generalized bullous eruption started at birth. The bullae were asymmetrically distributed all over the cutaneous surface and, over time, evolved into erosions that resolved with scarring areas. On the basis of the clinical picture and the ultrastructural and antigenic studies, a diagnosis of recessive dystrophic epidermolysis bullosa was made. In the following months, the patient began to complain a severe pruritus and the bullae and erosions were accompanied with diffuse erythematous patches and plaques covered by thick scale-crusts situated mostly on the arms. Microscopic examination of the scales revealed the presence of many mites and ova. Since the conventional topical therapies for scabies were uneffective, the patient was treated with a single dose (200 mcg/hg) of ivermectin. Although there was an initial improvement, scabies recurred within 2 months from discontinuation of the therapy. Finally, a further single administration of ivermectin at the same dosage led to the complete and permanent resolution of scabies. The association of recessive dystrophic epidermolysis bullosa and norwegian scabies has been already reported in literature. The case presented suggests that ivermectin represents an effective drug for severe forms of scabies occurring in patients affected by other dermatoses that prevent the use of topical treatments.

Infantile acute hemorrhagic edema of the skin.

Infantile acute hemorrhagic edema (AHE) of the skin is an uncommon form of cutaneous leukocytoclastic vasculitis that occurs in children younger than 3 years. We describe a 10-month-old boy with AHE, in whom the disease appeared after antibiotic treatment for an acute respiratory illness. AHE presented with fever, acral edema, and rosette-shaped purpuric plaques on the face and limbs. The causes of AHE are unclear, as is its nosologic position. Some authors consider the disease as a purely cutaneous form of Henoch-Schönlein purpura, and others believe that AHE should be regarded as a distinct clinicobiologic entity within the spectrum of leukocytoclastic vasculitis.

Correlation between clinical atypia and histologic dysplasia in acquired melanocytic nevi.

BACKGROUND: The validity of clinical and histologic criteria in identifying dysplastic nevi is controversial. Recognition of the dysplastic nevus as a distinct clinicopathologic entity requires demonstration of significant agreement between clinical atypia and histologic dysplasia. OBJECTIVE: We attempted to determine the correlation between clinical atypia and histologic dysplasia in acquired melanocytic nevi and to evaluate the sensitivity and specificity of clinical criteria for dysplastic nevi when compared with histopathologic features. METHODS: A total of 940 acquired melanocytic nevi 3 mm in diameter or larger were selected by initially choosing clinically unequivocal dysplastic and nondysplastic nevi and then, from these, histologically unequivocal dysplastic and nondysplastic lesions. The level of concordance between clinical atypia and histologic dysplasia was estimated by kappa statistics. RESULTS: Nevi were classified as clinically dysplastic (n = 499) or nondysplastic (n = 441). On the basis of histologic features, 739 were classified as dysplastic and 201 as nondysplastic. Agreement between clinical atypia and histologic dysplasia was found in 432 nevi, that is, a sensitivity of 58.4% (3-5 mm = 27.2%, >5 mm = 69.8%). Agreement between clinical and histologic criteria on the absence of dysplasia was found in 134 nevi, a specificity of 66.6% (3-5 mm = 92.4%, >5 mm = 47.9%). The kappa value was 0.17 (3-5 mm = 0.14, >5 mm = 0.10). CONCLUSION: The limited sensitivity and specificity together with the negligible kappa value indicate a poor agreement between clinical and histologic diagnoses of dysplastic nevus. The dysplastic nevus cannot be considered a distinct clinicopathologic entity because histologic dysplasia is found in a range of nevi that may or may not show clinical atypia.

Keratosis lichenoides chronica. Report of a case associated with B-cell lymphoma and leg panniculitis.

Keratosis lichenoides chronica (KLC) is a rare chronic dermatosis characterized by lichenoid hyperkeratotic papules arranged in a linear and reticular pattern, and seborrheic-dermatitis-like lesions on the face. Less frequently, palmoplantar keratoderma, nail dystrophies, mucosal as well as eye lesions are present. KLC affects adults and very few cases have been reported in childhood. Although infrequently, KLC has been associated with systemic diseases, including chronic infectious diseases, kidney disorders and lymphoma. Here we report the case of an adult KLC patient with skin, nail and mucosal involvement, and onset in the first year of life who developed a leg panniculitis and a mantle cell lymphoma. Following chemotherapy for the lymphoma, panniculitis resolved completely, and skin and mucosal KLC lesions ameliorated.

A clinicopathologic study of scarring alopecia due to lichen planus: comparison with scarring alopecia in discoid lupus erythematosus and pseudopelade.

The clinicohistologic findings in 68 patients with lichen planus scarring alopecia (LP) were compared with those of 25 patients with discoid lupus erythematosus of the scalp (DLE) and 25 with pseudopelade (PP). The combination of diffuse scaling, erythema, telangiectases, and mottled hyperpigmentation within areas of scarring alopecia was a distinctive feature of DLE, whereas the clinical picture of PP was indistinguishable from that seen in 29 patients with LP. In most patients with LP, the histologic changes involved only the follicles and the perifollicular dermis. Less frequently, the inflammatory process extended to the epidermis and the papillary dermis. In all cases, histopathologic features allowed LP to be distinguished from DLE regardless of the stage of the disease. The finding of a bandlike fibrotic thickening of the papillary dermis accompanied by fibrotic tracts at sites of destroyed follicles appeared to be a hallmark of "burnt out" lesions of LP. This histologic clue may be helpful in achieving a specific diagnosis of LP in cases that fulfill the clinical criteria for PP.

Melanocytic nevi of palms and soles: a histological study according to the plane of section.

Melanocytic nevi of palms and soles (MNPS) cause diagnostic problems to dermatopathologists because they share histologic features with malignant melanoma (MM). Early MNPS frequently display a striate appearance, suggesting that, in this subset of nevi, both melanocytes and melanin might have a particular distribution in relation to dermatoglyphics. To verify this hypothesis, we undertook a histological study on 78 junctional MNPS sampled along a plane either perpendicular or parallel to dermatoglyphics. Histologic examination revealed symmetry in 56% of the lesions, circumscription in 60%, intraepidermal scatter of melanocytes in 79%, and melanin columns in 61%. Interestingly, comparison between histologic features of nevi sampled perpendicularly and those of nevi cut parallely to dematoglyphics showed that features of benignity, namely symmetry, circumscription and melanin columns, were significantly more frequent in lesions dissected along a perpendicular plane. Moreover, in 70% of perpendicular samples, intraepidermal scatter of melanocytes and melanin columns were strictly concentrated in furrows. Therefore, to avoid diagnostic pitfalls in the differentiation between junctional MNPS and MM, we strongly suggest to dissect MNPS along a plane perpendicular to skin markings. We hypothesize that mechanical stress can be responsible for concentration of intraepidermal scatter of melanocytes and melanin columns in skin furrows.

Tufted folliculitis of the scalp: a distinctive clinicohistological variant of folliculitis decalvans.

Tufted folliculitis is an uncommon folliculitis of the scalp that resolves with patches of scarring alopecia within which multiple hair tufts emerge from dilated follicular orifices. The clinicohistological data from a group of 15 patients with tufted folliculitis were reviewed and compared with those of seven patients with folliculitis decalvans, five with acne keloidalis nuchae, four with dissecting cellulitis of the scalp, three with kerion celsi and 20 with follicular lichen planus. It was found that tufted folliculitis could be differentiated from folliculitis decalvans only by finding several hair tufts scattered within patches of scarring alopecia. Histologically, a single tuft consisted of peculiar clustering of adjacent follicular units opening at the bottom of an epidermal depression. Conversely, the presence of keloidal plaques in acne keloidalis nuchae, coalescing nodules discharging purulent material in dissecting cellulitis of the scalp, erythematous plaques covered by pustules replete with fungal elements in kerion celsi, and the absence of follicular pustules in follicular lichen planus distinguished these diseases from tufted folliculitis. On the basis of these findings, it is suggested that tufted folliculitis should be considered as a distinctive clinicohistological variant of folliculitis decalvans. Tufting of hair is caused by clustering of adjacent follicular units due to a fibrosing process and to retention of telogen hairs within the involved follicular units.

Primary cutaneous marginal zone B-cell lymphoma: a recently described entity of low-grade malignant cutaneous B-cell lymphoma.

Recently a new classification of primary cutaneous B-cell lymphomas (PCBCLs) has been proposed by the European Organization for Research and Treatment of Cancer (EORTC)--Cutaneous Lymphoma Project Group. The marginal zone B-cell lymphomas (MZLs) were not included as a distinct entity because of insufficient experience and controversial opinions. We have studied 32 patients (M:F ratio 1.5:1; age range 25-93 years; mean age 49.6 years; median age 50 years) to determine the diagnostic criteria of primary cutaneous MZL and the relationship with other low-grade malignant PCBCLs. For comparison, three patients with immunocytoma were included in the study. Clinically, patients presented with solitary or clustered reddish or red-brown papules, nodules, and plaques, sometimes surrounded by an erythematous halo. Histopathologic sections showed nodular or diffuse infiltrates involving the dermis and subcutaneous fat. Cytomorphologically small to medium-sized cells with indented nuclei and abundant pale cytoplasm (marginal zone cells, centrocyte-like cells) predominated. In addition, scattered blasts, lymphoplasmacytoid cells, and plasma cells were observed below the epidermis and at the periphery of the infiltrates. Reactive germinal centers were present in 75% of the cases. The three cases of immunocytoma showed a more monomorphous pattern with predominance of lymphoplasmacytoid cells. The marginal zone cells showed a CD20+, CD79a+, CD5- and Bcl-2+ immunophenotype. They expressed immunoglobulin G in the majority of the cases. Staining with the monocytoid B cell-related antibody KiM1p gave positive results in all specimens with a typical intracytoplasmic granular pattern. A monoclonal distribution of immunoglobulin light chains was observed in marginal zone cells in 75% of the cases. Germinal centers, when present, were either polyclonal or negative for both kappa and lambda light chains. Monoclonal rearrangement of the JH gene was detected via polymerase chain reaction (PCR) in 18 of 26 investigated specimens. Analysis in 12 patients of the bcl-2/immunoglobulin heavy chain gene rearrangement using PCR yielded negative results. Lesions were treated by surgical excision followed in some patients by local radiotherapy. Systemic antibiotic therapy was administered to three patients, with good response in two. The prognosis is excellent. After a mean follow-up of 47.9 months (range 6-252; median 24) all patients are alive without signs of systemic lymphoma. Primary cutaneous MZL represents a distinct clinicopathologic subtype of low-grade malignant PCBCL.

Neutrophilic figurate erythema of infancy.

We describe a transient figurate erythema in an 11-month-old female infant with a 2-month history of arcuate and annular erythematous lesions localized on the face, trunk, and limbs. Constitutional symptoms were absent. Previous medical history was unremarkable. Full blood examination, erythrocyte sedimentation rate, antistreptolysin-O titer, anti-Ro, and anti-La antibodies were within normal limits or negative. Histologic examination revealed a superficial and deep perivascular and interstitial dermatitis constituted mostly of neutrophils and abundant nuclear dust. The lesions resolved spontaneously within a few months without scarring or atrophy. Recurrence has not occurred. This case suggests that figurate erythemas in infants rarely may disclose a neutrophilic histologic pattern, which must be differentiated from that of other neutrophilic dermatoses.

p53 mutations and chromosome instability in basal cell carcinomas developed at an early or late age.

Tumor DNA from 45 primary basal cell carcinoma (BCC) biopsies was screened for p53 gene mutations, chromosome 9 allele loss, and microsatellite instability. p53 mutation frequency increased significantly as a function of the age at BCC onset ranging from 6% (1/16) in early BCC (before age 40 years) to 35% (10/29) in late BCC. All p53 mutations found implicated sunlight as the mutagen. Chromosome 9 instability (allele loss or microsatellite instability) was detected at high frequency (38%) independently of age at tumor onset. Allelic loss was confined to chromosome 9q, whereas microsatellite instability was observed prevalently on chromosome 9p often in association with a replication error (RER+) phenotype. Most of our late BCC patients reported occupational sun exposure, while early BCC patients recalled childhood (0-20 years) recreational sun exposure. These data suggest that chronic exposure to sunlight is responsible for accumulation of p53 mutations and thus for late BCC appearance, whereas acute UV exposure in childhood and adolescence leads to early skin cancer development in genetically susceptible individuals via a p53-independent pathway.

Minimally differentiated acute myeloid leukaemia revealed by specific cutaneous lesions.

Minimally differentiated acute myeloid leukaemia (AML-MO) is a poorly differentiated type of acute myeloid leukaemia. Its myeloid differentiation can only be demonstrated by the immunohistochemical or ultrastructural finding of cytoplasmic myeloperoxidase in bone marrow blasts and/or by the immunohistochemical expression of at least one lineage-specific myeloid antigen, with no reactivity for lymphoid antigens. We describe a man with a cutaneous nodular eruption that represented the first clinical manifestation of AML-MO. Histological examination showed extensive proliferation of blasts with scant basophilic cytoplasm. Immunohistochemically, these expressed neither myeloid nor lymphoid-specific antigens, whereas they were focally positive for CD45. The diagnosis of AML-MO was confirmed by immunophenotypic analysis of a bone marrow smear. A complete remission was achieved following parenteral steroid therapy. The disease relapsed some months later, and the patient died within a few weeks.

Papular clear cell hyperplasia of the eccrine duct in a diabetic.

We report a patient with a widespread papular disorder characterized by extensive clear cell hyperplasia of the secretory portion of the eccrine units. A 46-year-old woman had a long history of diffuse papules which gave the skin a 'goose-flesh' appearance. She had severe diabetes. Histological examination of a papule showed marked clear cell hyperplasia that involved the secretory duct of all eccrine units present in the specimen sparing the secretory coil. The clear cells were periodic acid-Schiff (PAS) positive and Alcian blue negative. Ultrastructural study confirmed that the clear cells contained abundant intracytoplasmatic glycogen. We suggest that the diabetic condition may be important in promoting the accumulation of glycogen in the eccrine ducts. Our patient represents a peculiar disorder of the eccrine units that, on the basis of clinicopathological features, we have termed papular clear cell hyperplasia of the eccrine duct.

Purely cutaneous Rosai--Dorfman disease.

Cutaneous lesions of Rosai-Dorfman disease (RDD) are usually associated with nodal or other extranodal localization. We describe a female patient with RDD clinically limited to the skin. The patient presented with asymptomatic red-brown papules and nodules on the legs, arms, back, and nose. Histologically, the lesions consisted of a proliferation of large histiocytes occasionally showing emperipolesis. Histiocytes were also observed within dilated lymphatic vessels. Immunohistochemical study showed that histiocytes expressed S-100 protein and both macrophage and monocyte markers. All lesions resolved completely with Roentgen therapy. No recurrence has been observed over a 3-year follow-up period.