bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kimura's disease and angiolymphoid hyperplasia with eosinophilia: New observations from immunohistochemical studies of lymphocyte markers, endothelial antigens, and granulocyte proteins
Authors: Helander Steven D. , Peters Margot S. , Kuo Tseng‐long , Daniel Su W. P. 
Published: April 2006

Kimura's disease (KD) typically presents as large subcutaneous masses in young Oriental males. It is characterized by deep inflammation with vascular proliferation, lymphocytic nodules with subcutaneous germinal centers, fibrosis, and edema. In comparison, angiolymphoid hyperplasia with eosinophilia (ABLE) occurs in all races and the lesions usually are smaller and more superficial. The causes of diese two diseases are debated.We compared histologic features of 4 cases of KD with 22 cases of ALHE and studied expression of endothelial antigens and lymphocyte markers as well as localization of eosinophil, mast cell, and neutrophil granule proteins in lesional tissue. T‐cell lymphoid aggregates with well‐formed B‐cell germinal centers occurred in KD, and nodular and diffuse T‐cell infiltration with small B‐cell clusters occurred in ALHE. Endothelial proliferation was more pronounced in KD, lacking the atypical histiocytoid endothelial cells characteristic of ALHE. Many intact eosinophils infiltrated lesions in both diseases, although KD had less extracellular granule protein deposition than ALHE. Intact mast cells were seen in both diseases. There was neutrophil elastase staining of occasional scattered intact cells but no extracellular deposition. Compared with KD, ALHE is more varied in its clinical, histopathologic, and immunohistochemical features.
Immunohistochemistry of dermatofibromas and benign fibrous histiocytomas
Authors: Prieto Victor G. , Reed Jon A. , Shea Christopher R. 
Published: April 2006

Dermatofibromas (DF) are common, benign skin tumors composed predominantly of cells having elongated nuclei and very scant cytoplasm (i.e., fibroblasts) and capillaries in a collagenous stroma. Some authors distinguish DF from benign fibrous histiocytomas (BFH), which are composed of cells with round to oval nuclei and abundant cytoplasm (i.e., histiocytes). In general, this group of tumors expresses factor XIIIa but not the antigen recognized by MAC 387. However, immunohistochemical differences specifically between DF and BFH have not been reported.We have studied the immunophenotype of 23 lesions having morphologic features predominantly either of DF (17 cases) or BFH (6 cases) using antibodies against desmin (muscle marker), α‐smooth‐muscle actin (muscle and myofibroblast marker), CD68 and HAM56 antigen (markers commonly expressed by macrophages, so called “histiocytic” markers), CD34 (a marker present in hematopoietic, vascular, and occasional dermal dendritic cells), and factor XIIIa (a transglutaminase present in many cells including dermal dendrocytes). Many spindle‐shaped cells expressed a‐smooth‐muscle actin while many large, round cells expressed the histiocytic markers. However, most lesions expressed at least focally both α‐smooth‐muscle actin and “histiocytic” markers. Thus a clear‐cut distinction between DF and BFH could not be made based on immunophenotype alone. Additionally, the prominent α‐smooth‐muscle actin immunoreactivity and desmin non‐reactivity suggests myofibroblastic differentiation in the spindle‐cell regions of these tumors, and indicates that expression of a‐smooth‐muscle actin cannot be used as definitive proof of muscle differentiation in spindle‐cell tumors. We conclude that DF and BFH are not discrete entities, but represent polar expressions of one nosologic entity exhibiting both myofibroblastic and “histiocytic” differentiation.
The use of Michel's transport medium for immunofluorescence and immunoelectron microscopy in autoimmune bullous diseases
Authors: Vaughan Jones S.A. , Palmer I. , Bhogal B. S. , Eady R. A. J. , Black M.M. 
Published: April 2006

We report the use of Michel's solution, already a well established transport medium, in the combined use of direct immunofluorescence (IMF) and pre‐embedding immunoelectron microscopy in 3 subepidermal bullous diseases ‐ bullous pemphigoid (BP), epidermolysis bullosa acquisita (EBA) and dermal binding linear IgA disease (LABD). Our studies demonstrated that electron microscopy of normal skin maintained in Michel's medium for up to 28 clays showed remarkable preservation of all components of the basement membrane zone, including the ultrastructure of the basal keratinocytes, dermoepidermal junction and papillary dermis. However, epidermal cell cytolysis occurred after just 48 hours.Immunoelectron microscopy using a gold probe has enabled us to localise the immunoreactants in bullous pemphigoid, epidermolysis bullosa acquisita and dermal‐binding linear IgA bullous dermatoses. Our findings are comparable to and as equally reliable as those on immunoelectron microscopy of fresh skin biopsies with no loss of antigen deposition, and demonstrate an effective new use of a well established transport medium.
In vivo expression of the insulin‐like growth factor‐I (IGF‐I) receptor in congenital pigmented nevi
Authors: Hodak E. , Gottlieb A.B. , Colen S. , Anzilotti M. , Krueger J.G. 
Published: April 2006

Growth of normal melanocytes, nevus cells and primary melanoma cells is enhanced by insulin/insulin‐like growth factor‐I (IGF‐I) in vitro. It has been shown that a melanoma cell line possesses the IGF‐I receptor which plays a role in activation of the chemotactic response. Little is known about the in vivo expression of the IGF‐I receptor and its role in melanocytic lesions. In an immunohistochemical study, we investigated the expression of IGF‐I receptor in frozen sections of congenital pigmented nevi from 10 patients (ages 8 months to 4 yrs) using the monoclonal antibody αIR3, which specifically recognizes the extracellular alpha subunit of the IGF‐I receptor. The proliferative activity of the nevus cells was examined by staining with Ki67 monoclonal antibody (reactive with all actively cycling cells). IGF‐I receptor was found to be widely expressed by the cell surface of the nevus cells. Membrane staining was occasionally stronger in the superficial portion of the congenital pigmented nevi. In contrast, Ki67‐positive cells were only sparsely scattered throughout the nevi with some tendency to localization to the superficial portion.This study indicates that in vivo the IGF‐I receptor is widely expressed by congenital pigmented nevus cells. As opposed to keratinocytes, in which IGF‐I receptor expression defines the proliferation pool of the normal and disordered epidermis, the IGF‐I receptor is expressed by all nevus cells, irrespective of their proliferative status.Further studies are needed to assess whether the IGF‐I receptor expression can serve as a marker for increased risk for development of malignancy in various types of benign melanocytic lesions.
The role of αEβ7 integrin (CD103) and E‐cadherin in epidermotropism in cutaneous T‐cell lymphoma
Authors: Dietz Stephanie B. , Whitaker‐Menezes Diana , Lessin Stuart R. 
Published: April 2006

Adhesion molecules such as integrins and cadherins are thought to play a critical role in T‐cell migration and localization within the epidermis (epidermotropism). The purpose of this study was to correlate T‐cell expression of the integrin GD103 and E‐cadherin in cutaneous T‐cell lymphoma (CTCL). Serial sections of skin biopsies from 22 patients with CTCL and 13 with benign reactive dermatitis were stained with antibodies to CD4, CD103, and E‐cadherin by the avidin‐biotin peroxidase technique. CD 103 was expressed on single epidermotropic CD4+ T‐cells in 9/9 early stage (patch/plaque) CTCL and 6/10 reactive dermatitis biopsies. Less than 30% of dermal T‐cells expressed CD103. All 4/4 late stage (tumor) CTCL were GD103–. Epidermal aggregates of CD4+T‐cells (Pautrier's microabscesses) were CD103–. E‐cadherin was expressed on epidermal keratinocytes and follicular and sweat gland epithelia but not on T‐cells.We conclude that CD 103 expression on cutaneous T‐cells parallels the degree of epidermotropism exhibited in both neoplastic and inflammatory disorders of the skin. E‐cadherin is not expressed on T‐cells infiltrating the skin. Further investigation is necessary to further elucidate the interaction between CD103 and E‐cadherin in facilitating trafficking of T‐cells into the epidermis.
Nuclear morphometry, immunohistochemical staining with Ki‐67 antibody and mitotic index in the assessment of proliferative activity and prognosis of primary malignant melanomas of the skin
Authors: Talve Lauri Arvo Ilmar , Collan Yrjö Urho Ilmari , Ekfors Tauno Olavi 
Published: April 2006

Nuclear morphometry, immunohistochemical staining with Ki‐67 antibody and mitotic index were studied in primary cutaneous malignant melanomas. The number of Ki‐67 positive cells/200 tumor cells did not correlate with any nuclear morphometrical parameters, and it only approached but did not reach significant correlation with melanoma thickness according to Breslow. The nuclear area, short axis and long axis correlated with melanoma thickness, but the nuclear axis ratio (which reflects the sphericity of nuclei) and melanoma thickness did not show significant correlation. Mitotic index was higher in thick melanomas and in melanomas with high Ki‐67 positivity, large nuclear area, long nuclear short axis, and small nuclear axis ratio. In Cox's stepwise proportional hazard model, melanoma thickness and the nuclear axis ratio were significant independent prognostic factors for patient survival, while the nuclear area, short axis and long axis, gender, age, Clark level, mitotic index and Ki‐67 positivity lacked significant independent prognostic value.The results suggest that the proliferative activity of tumor cells does not alone explain the great importance of tumor thickness as prognosticator in melanoma. The thickness of melanoma measured according to Breslow and the nuclear axis ratio are more efficient prognosticators in melanoma than parameters associated with proliferation.
Role of Borrelia burgdorferi in the pathogenesis of morphea/scleroderma and lichen sclerosus et atrophicus: a PCR study of thirty‐five cases
Authors: DeVito James R. , Merogi Athir J. , Vo Thao , Boh Erin E. , Fung Hank K. , Freeman Scott M. , Cockerell Clay , Stewart Kelly , Marrogi Aizen J. 
Published: April 2006

Morphea (localized scleroderma), and lichen sclerosus et atrophicus (LSA) share common features with acrodermatitis chronica atrophicans (ACA), a known chronic form of borreliosis. These include similar histologic findings such as diffuse dermal fibrosis. These observations have led several investigators to consider the possibility of Borrelia burgdorferi (Bb) as a common etiologic factor among all of these diseases.The aim of this study is to investigate the role of Bb in the pathogenesis of morphea and LSA, by assaying for its presence in lesional skin biopsies from patients with these diseases. We utilized the nested polymerase chain reaction (PCR) technique to selectively amplify a longer segment of a Bb‐specific somatic gene, on DNA from paraffin‐embedded, formalin‐fixed tissues. The results revealed no Bb‐specific DNA sequence in 28 specimens of morphea/scleroderma and 7 of LSA with varying stages of disease. Furthermore, confirmatory Southern blot of the PCR product, resulted in similar findings. These data seriously question the role played by this spirochete in the pathogenesis of morphea and LSA, at least in the southeastern part of the USA.
Fibro‐osseous pseudotumor of the digit: a comparison to myositis ossificans by light microscopy and immunohistochemical methods
Authors: Sleater J. , Mullins D. , Chun K. , Hendricks J. 
Published: April 2006

Fibro‐osseous pseudotumor of the digit is an unusual cutaneous process characterized histologically by a fibroblastic proliferation admixed with reactive/metaplastic osteoid formation. The osteoid formation can be florid and immature, mimicking the appearance of malignant osteoid‐forming neoplasms. Fibro‐osseous pseudotumor of the digit has histologic and clinical features in common with myositis ossificans. This has led many to consider the two to be synonymous. We studied three cases of fibro‐osseous pseudotumor, compared to five cases of myositis ossificans, using routine light microscopy and a battery of immunohistochemical stains.Both entities displayed a “zoning” pattern of immature spindled areas admixed with more mature areas having osteoid metaplasia. This was more pronounced in myositis ossificans. In each lesion, the spindle cells stained positively for vimentin and actin. CD34 and Factor VIII highlighted the vasculature. No stromal staining for MAK‐6 (cytokeratin) or S‐100 was identified. Ki‐67, a proliferation marker, showed positive staining of the stromal cells in both lesions, which was strongest in the immature spindled areas. The immunohistochemical and histologic similarities of the lesions support fibro‐osseous pseudotumor of the digit being a cutaneous variant of myositis ossificans.
Modulation of epidermal differentiation, tissue inflammation, and T‐lymphocyte infiltration in psoriatic plaques by topical calcitriol
Authors: Lu Irene , Gilleaudeau Pat , McLane John A. , Heftier Noah , Kamber Markus , Gottlieb Scott , Krueger James G. , Gottlieb Alice B. 
Published: April 2006

Psoriasis is characterized by immune activation, increased proliferation and abnormal differentiation of keratinocytes. The reported anti‐psoriatic mechanisms of action in vivo of vitamin D analogues include reduction of keratinocyte proliferation and induction of keratinocyte terminal differentiation.We investigated whether the anti‐psoriatic effect of the natural active vitamin D analogue, calcitriol, applied topically, is due to direct effects on keratinocytes alone or also due to immunoregulatory effects of calcitriol.Psoriasis patients were treated with topical calcitriol (0.005%) and a vehicle control for 8 weeks. Disease activity was assessed by a severity index and quantitative histopathological markers. In vitro studies of lymphocyte proliferation and gamma interferon secretion and of keratinocyte proliferation complemented the clinicohistopathologic studies.A heterogeneous response to calcitriol treatment could be segregated based upon elimination of K‐16 keratin expression. Calcitriol treatment decreased keratinocyte proliferation, normalized keratinocyte differentiation and decreased immune activation in plaques.The histologic response to vitamin D treatment of psoriasis includes suppression of both immune and keratinocyte activation in situ. These studies provide a basis for rational combination of anti‐psoriatic treatments and for the design of new vitamin D analogues to treat psoriasis.
Cutaneous adult myofibroma: a vascular neoplasm
Authors: Requena Luis , Kutzner Heinz , Hügel Heino , Rütten Arno , Furio Vicente 
Published: April 2006

Infantile myofibromatosis is a distinctive type of fibromatosis that usually develops during the immediate perinatal period. There are variants with solitary and multiple tumors. Lesions confined to the skin, soft tissue, and bone carry a good prognosis, showing spontaneous regression. The prognosis, however, is much less favorable when visceral lesions are present and the outcome may be fatal. Only recently it became obvious that there is an adult counterpart of infantile myofibromatosis, characterized by solitary lesions that have a predilection for involve the dermis and show no tendency to regression, although they have an entirely benign biological behavior. These lesions have been named cutaneous myofibroma or solitary myofibroma of adults.We have studied the clinical, histopathological and immunohistochemical characteristics of 53 examples of cutaneous adult myofibroma. In addition, 2 cases were examined ultrastructurally. The patients were mostly adults with ages ranging from 6‐83 years. The lesions presented as solitary, usually painless nodules of variable duration on the skin, usually located on the extremities. Histopathologically, four patterns were identified: nodular or cellular type, multinodular or biphasic type, leiomyoma‐like or fascicular type, and vascular type. A correlation between the histopathologic pattern and the lesional age was observed: vascular type of cutaneous adult myofibroma in early lesions, nodular and multinodular lesions in fully developed lesions, and leiomyoma‐like or fascicular type in late lesions. Immunohistochemically, the spindle cells were desmin negative, but expressed immunoreactivity for vimentin, pan‐smooth muscle actin, and alpha‐smooth muscle actin. Ultrastructurally, neoplastic cells showed characteristics of undifferenciated mesenchymal cells with features of fibroblasts, myofibroblasts and pericytes. Primitive vascular formations were seen in the form of irregular clefts between adjoining cells.We conclude that cutaneous adult myofibroma is a little‐known benign vascular neoplasm probably derived from myopericytes.
p75 nerve growth factor receptor staining helps identify desmoplastic and neurotropic melanoma
Authors: Kanik A. B. , Yaar M. , Bhawan J. 
Published: April 2006

Melanoma is a malignant tumor with a varied histologic appearance. Melanoma composed of spindle cells may include desmoplastic and neurotropic melanoma. The histologic diagnosis of desmoplastic and neurotropic melanoma can be difficult. Although S100 protein stains a majority of these melanomas, die staining may be weak or focal. HMB‐45, a more specific marker of melanoma, is frequently negative in desmoplastic and neurotropic melanoma.In order to aid the identification of desmoplastic and neurotropic melanoma, we stained 13 spindle cell melanomas (5 neurotropic melanomas, 5 desmoplastic melanomas, 3 spindle cell melanomas without either desmoplasia or neurotropism) with p75 NGF‐R and compared the staining results with S100 and HMB‐45. p75 NGF‐R is the low affinity nerve growth factor receptor reported to be present on the surface of neural‐crest‐derived cells. Conventional melanoma as well as neurotized nevi, neurofibroma, spindle squamous carcinoma, atypical fibroxan‐thoma, dermatofibroma and scars were also stained with p75 NGF‐R.p75 NGF‐R stained all of the desmoplastic and neurotropic melanomas tested. In each of these cases, negative HMB‐45 staining of the spindle cells was seen. In many cases the number and intensity of the spindle cells staining with p75 NGF‐R was greater than with S100. Neurofibroma, neurotized nevi and focal cells in round cell melanoma also were stained with p75 NGF‐R. All the squamous cell carcinomas, atypical fibroxanthomas, dermatofibromas and scars were negative for p75 NGF‐R.Based on our results, p 75 NGF‐R may be useful as an additional confirmatory antibody in a melanoma panel, especially in differentiating desmoplastic and neurotropic melanomas from non‐neural‐crest‐derived spindle cell lesions. We feel it also can be helpful in better identifying margins of excision of these melanomas. p75 NGF‐R, like S100 protein, will not differentiate desmoplastic and neurotropic melanomas from other neural‐crest‐derived lesions.
Histologic criteria for the diagnosis of erythrodermic mycosis fungoides and Sézary syndrome: a critical reappraisal
Authors: Kohler Sabine , Kim Youn H. , Smoller Bruce R. 
Published: April 2006

It is often difficult to make a clinical or histologic diagnosis of erythrodermic mycosis fungoides (MF) and Sézary syndrome (SS). Whereas the histologic parameters for making a diagnosis of MF with well‐developed patch and plaque stage lesions are clearly defined, the same criteria appear to be less relevant for diagnosing MF in patients with erythroderma secondary to the disease. In order to better define the histologic features of erythrodermic MF and SS, we studied 28 routine histologic sections of 17 patients with known erythrodermic MF or SS. Sections were reviewed independently by 2 dermatopathologists. Each of 24 parameters was scored semi‐quantitatively and the data were compared to data previously reported from a group of 64 patients with limited patch and plaque stage lesions of MF. When compared to biopsies from patients with limited patch/plaque lesions, biopsies taken from erythrodermic patients displayed more parakeratosis (p=0.0492) and acanthosis (p=0.0046), less disproportionate epidermotropism, fewer lymphocytes aligned within the basal layer (p=0.0045), fewer hyper‐convoluted cells in the epidermis, more dermal hyperconvoluted cells (p=0.0191), more papillary dermal fibrosis (p=0.0002), more prominent teleangiectasias (p=0.0028) and more mitotic figures.The histologic features of erythrodermic MF and Sézary syndrome are even more subtle than the features of patch and plaque stage MF, thus rendering the histologic diagnosis more difficult.
Identification of aneuploidy in recurrent clear cell hidradenoma by DMA image cytometry (ICM‐DNA)
Authors: Kiehl Peter , Vakilzadeh Fereydoun , Richter Klaus , Kapp Alexander , Böcking Alfred 
Published: April 2006

Since malignant clear cell hidradenoma (CCH) is often characterized by only slight and sometimes by absent nuclear anaplasia, even in metastases, definitive differentiation from its benign counterpart by light microscopy may be very difficult.Herein, we report the case of a 72‐year‐old woman suffering from a CCH on the back, which showed local recurrence following incomplete excision. By light microscopy no unequivocal signs of malignancy were found either in the primary or the recurrent tumor. However, unusual deep extension to the subcutis with some architectural disorder was seen in the latter.Identification of prospective malignancy in such cases of borderline histopathological features is one of the main indications for diagnostic DNA image cytometry (ICM‐DNA). Application of this method to enzymatic cell separation specimens of the recurrence detected marked DNA‐aneuploidy with a stemline ploidy of 2.60 c and single events up to 6.7 c, whereas a nearly exact diploid DNA‐stemline was found in the primary.We suppose from our results that a prospective malignant CCH with aneuploid DNA‐stemline has developed out of its DNA‐diploid counterpart. The need for total surgical removal of apparently benign clear cell hidradenomas is further stressed by this observation.Criteria for the diagnosis of malignancy in CCH are reviewed.
Interphase cytogenetic demonstration of chromosome 9 loss in thick melanomas
Authors: Wolfe K. Q. , Southern S. A. , Herrington C. S. 
Published: April 2006

It has been postulated that deletion of genes on chromosome 9 is important in the development of malignant melanoma. In this study, we have investigated this hypothesis by analysing the numerical complement of chromosomes 9, 17 and X by interphase cytogenetics using peri‐centromeric repeat probes on paraffin sections from 15 thick melanomas. Three cases showed no relative loss or gain of chromosomes. Two cases showed gain of chromosome 17, and one case loss of chromosome 17 relative to chromosomes 9 and X.Relative chromosome 9 loss was identified in 9 cases (60%). Two of these were monosomic for chromosome 9 with a normal complement of chromosomes 17 and X and six were tetrasomic for chromosome 17 with duplication of chromosome X: chromosome 9 was disomic in five of these cases and trisomic in one. The final case showed loss of both chromosomes 9 and 17 relative to X. The chromosome patterns obtained imply that loss of chromosome 9 frequently takes place before tetraploidisation. This is in keeping with the hypothesis that loss of chromosome 9 is not a late event in melanocyte transformation. Extension of these studies to thin melanomas, in situ melanomas and dysplastic naevi will refine further the point at which these changes occur.