bluuebunny/crossref_metadata_2025 huggingface dataset:
The pathogenesis of the transepithelial elimination of the collagen bundles in acquired reactive perforating collagenosis
Authors: Yanagihara Makoto , Fujita Tomozo , Shirasaki Atsuko , Ishiguro Kazumori , Kawahara Ken‐Ichi , Ueda Keiichi
Published: April 2006

Two cases of acquired reactive perforating collagenosis with poorly controlled diabetes mellitus were studied by histochemistry and by electron microscopy. In excoriated wounds, the necrotic mass on the bottom of the ulcer contained the collagen bundles which were continuous with the collagen bundles in the reticular layer. In the developing stage, the epidermis regenerated between the necrotic mass and the reticular dermis, and the collagen bundles in the reticular dermis were in continuity with those in the necrotic mass through the epithelial tunnels. The collagen in the epidermal channels did not degenerate ultra‐structurally. In the mature lesion, collagen bundles being eliminated through the epidermis were surrounded by the fibroblasts at the basal cell layer. Collagen fibers were seen in the cytoplasm of these fibroblasts. From these findings, the mechanisms of the formation of the eruption in acquired reactive perforating collagenosis might be as follows: 1) In the developing stage, the regeneration of epidermis progresses between the necrotic mass and the reticular dermis, and among the collagen bundles. As a result, the collagen bundles remain in the channels of the epidermis. And then, 2) the regenerated epidermis makes the thick horny layer. As a result, the necrotic masses are lifted up and the collagen bundles are pulled up from the dermis through the epidermal channels.
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.
Solitary cutaneous myofibromas in adults: report of six cases and discussion of differential diagnosis
Authors: Guitart Joan , Ritter Jon H. , Wick Mark R.
Published: April 2006

Six solitary, dermal or subcutaneous lesions occurring in adult patients are presented. These masses had a circumscribed, lobulated configuration; they were composed of fusiform and epithelioid cells that lacked atypical nuclear features. The pattern of growth featured fascicles and nests, a myxofibrous stroma, and prominent blood vessels with a focally “hemangiopericytoid” appearance. Immunohistochemical analyses showed uniform reactivity for vimentin and alpha isoform‐actin, with negativity for desmin and neural determinants. The overall appearance of the lesions was similar to that of “infantile myofibromastosis,” and corresponded to previous descriptions of “solitary myofibroma(tosis)” in adults. Immunophenotypic and ultra‐structural support exists for a proposed myofibroblastic nature for such proliferations. Differential diagnostic considerations include neurothekeomas, plexiform fibrous histiocytomas, nodular fasciitis, cutaneous inflammatory pseudotumors, dermatomyofibromas, leiomyomas, and other forms of fibromatosis affecting the skin and superficial soft tissues.
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.
Involvement of the adherens junction – actin filament system in acantholytic dyskeratosis of Hailey‐Hailey disease
Authors: Metze Dieter , Hamm Henning , Schorat Annette , Luger Thomas
Published: April 2006

Hailey‐Hailey disease is a blistering genodermatosis that shows acantholytic dyskeratosis throughout the epidermis. The aim of our study was to investigate the involvement of adherens structures and cytofilaments in this particular type of acantholysis. Both lesional and non‐lesional skin from 18 patients was studied histologically and ultrastructurally. Additionally, the samples were stained for desmosomes, adherens junctions, keratin filaments, actin filaments, and actin‐associated proteins, and finally investigated with an electron and a confocal laser scanning microscope (CLSM), respectively. Acantholytic dyskeratosis was not only confined to lesions, but was also focally detectable in clinically unaffected skin. Despite disruption and internalization of the desmosomes, keratinocytes remained linked together by well‐preserved adherens junctions. Staining for actin filaments with fluorochrome‐labeled phalloidin showed a remarkable formation of actin stress fibers in these keratinocytes. Thus, incomplete acantholysis, as demonstrable in both lesional and non‐lesional skin of Hailey‐Hailey patients, may be due to a cohesive function of the adherens junction‐actin system succeeding the dissolution of desmosomes. Most remarkably, none of the adnexal epithelia expressed the intrinsic defect of cell adhesion. This finding offers an explanation for the successful treatment of Hailey‐Hailey disease by dermabrasion, which after complete removal of the involved epidermis results in reepithelialization from skin appendages.
VLA and α6β4 integrin expression in neuroendocrine carcinomas of the skin (their xenografts on nude mice and a corresponding primary culture)
Authors: Perrin C. , Pisani A. , Demarchez M. , Michiel J. F. , Ortonne J. P.
Published: April 2006

Immunohistological expression of VLA1–5 and α6β4 integrins have been studied in 21 cases of primary neuroendocrine carcinomas of the skin (NECS), three xenografts on nude mice and one NECS cell culture. The phenotypic properties of NECS cells were largely maintained in NECS grafted on athymic nude‐mice and in the corresponding cell line. Our results indicate that α1β1 and to a lesser extent α3β1,α5βl are the main integrins expressed in NECS. In addition, VLA2,4 and α6β4 are heteroge‐neously expressed in the same group of tumors and very sparsely present. These data suggest that like neuroblastoma and primitive peripheral neuroectodermal tumor (pPNET) the absence or the heterogeneous distribution of such integrins is correlated with the aggressive behaviour of NECS although long‐term follow‐up was not available for our cases. On the other hand, the α1 expression could be regarded as a novel marker for differential diagnosis between NECS (α1+) and pPNET (α1−). The α1β1, α2β1, α3β1, α5βl heterodimers in the 21 NECS studied showed an uniform pericellular staining of both the peripheral cells and central cells of the tumor islands. The predominant expression of α1β1 is consistent with the hypothesis of a primitive epithelial totipotential origin in NECS.
p53 immunoreactivity in non‐melanoma skin cancer from immunosuppressed and immunocompetent individuals: a comparative study of 246 tumours
Authors: Khorshid S.M. , Glover M.T. , Churchill L , McGregor J.M. , Proby C.M.
Published: April 2006

p53 immunoreactivity was examined in 132 cutaneous non‐melanoma tumours from renal transplant recipients and in 114 histologically matched specimens from immunocompetent individuals. Skin lesions examined included 52 viral warts, 50 clysplastic keratoses, 51 intraepidermal carcinomas (IEC), 50 invasive squamous cell carcinomas (SCC) and 43 basal cell carcinomas (BCC). Overall, 51% (51/101) pre‐malignant skin lesions and 45% (42/93) non‐melanoma skin cancers (NMSC) showed p53 immunoreactivity, with extensive (> 50% cells positive) p53 staining in 27% (27/101) of pre‐malignant and 20% (19/93) of malignant lesions. 17% (9/52) viral warts showed p53 immunoreactivity, but this was limited to focal or basal p53 staining. p53 immunoreactivity in all tumours was less in transplant than in non‐transplant patients and this reached statistical significance for SCCs (p = 0.03).
Perivascular mast cells in urticaria pigmentosa
Authors: Sweet William L. , Smoller Bruce R.
Published: April 2006

We have quantified perivascular mast cells in cases of urticaria pigmentosa, urticaria, and dermal hypersensitivity reactions. To facilitate reproducibility, the mast cells were counted for a precisely defined vessel unit. These vessel units were divided arbitrarily into those ≤55μm and > 55μm in largest diameters. Urticaria pigmentosa showed an average of 6.4 ± 1.9 and 22.8 ± 13.2 masts cells for vessel unit ≤ 55μm and ≤ 55μm, respectively. Urticaria yielded a lower number of mast cells: 1.5 ± 0.2 and 2.9 ± 0.9 for the same respective vessel units. Dermal hypersensitivity reactions revealed an average of 1.6 ± 0.4 and 2.2 ± 0.7 mast cells, and the normal skin showed 1.5 ± 0.3 and 2.4 ± 0.6 mast cells for each of the vessel units of ≤ 55μm and > 55μm. The perivascular mast cell distributions of urticaria pigmentosa are statistically different from those of urticaria and dermal hypersensitivity reactions with p < 0.0001. No statistical difference was noted between urticaria, dermal hypersensitivity reactions, and normal skin. The percentages of vessel units ≤ 55μm with ≥ 5 mast cells and vessel units < 55μm with ≥ 10 mast cells were determined for each case. The average percentage of vessel units for the former and latter in urticaria pigmentosa was 82.6% and 58.9%, respectively. Urticaria yielded 0% and 0.2%, respectively. None of vessel units in the dermal hypersensitivity reactions or normal skin contained more than 5 mast cells in vessel units ≤ 55μm and more than 10 mast cells in vessel units > 55μm. Cases of urticaria pigmentosa can be distinguished from other cutaneous eruptions containing mast cells using a simple counting technique on Giemsa stained sections.
Mucinous differentiation in adnexal sweat gland tumors
Authors: Fitzgibbon James F. , Googe Paul B.
Published: April 2006

We report an ecerine acrospiroma, on the cheek of a 29‐year‐old female, in which the presence of abundant mutinous (goblet cell) metaplasia closely mimicked a primary mucoepidermoid carcinoma. To determine the frequency of mutinous differentiation in benign adnexal sweat gland tumors, we evaluated sixty‐five cases in hematoxylin and eosin stained sections for the presence of goblet cells and sixty of these for mucicarmine positivity. Goblet cell metaplasia was seen in 3 of 12 acrospiromas, 1 of 8 mixed tumors, and in 1 of 9 cases of syringocystadenoma papil‐liferum. All goblet cells were positive for mucicarmine, except in one case of acrospiroma, where goblet cells were not detected on the section stained with mucicarmine. In addition, intracellular mucin, inclusive of goblet cells, was seen in 5 of 12 acrospiromas, 1 of 11 poromas, 5 of 8 mixed tumors, 3 of 13 spiradenomas, 1 of 5 cylindromas, 3 of 9 cases of syringocystadenoma papilliferum and 1 of 3 nipple adenomas. The majority of the tumors had both extracellular mucicarmine positivity (40 of 60) and luminal mucicarmine positivity (39 of 60). We conclude that mutinous differentiation in sweat gland tumors, as defined by the presence of goblet cells and/or intracellular mucicarmine positivity, is common and does not indicate aggressive behavior. Mucinous differentiation in benign sweat gland tumors should not be confused with more aggressive mucoepidermoid carcinomas of salivary gland origin or adenosquamous carcinoma.
Pityriasis rubra pilaris with acantholysis
Authors: Howe K. , Foresman P. , Griffin T. , Johnson W.
Published: April 2006

Two patients* developed a papulosquamous eruption in a widespread distribution which progressed with islands of sparing of uninvolved skin characteristic clinically of adult‐onset pityriasis rubra pilaris (PRP). Biopsies from both patients showed multiple areas of nonfollicular and follicular suprabasilar and intra‐epidermal acantholysis with minimal dyskeratosis. They also showed the usual histologic features of PRP with a thickened orthokeratosis and parakeratosis, a retained and sometimes thickened granular cell layer, and psoriasiform epidermal hyperplasia with a perivascular lymphohistiocytic infiltrate in the superficial dermis. Two previous patients with PRP have been reported with nonfollicular, focal acantholytic dyskeratosis and both were interpreted as most likely representing an incidental finding. We believe the acantholysis in these two cases is related to the disease process, and in our second patient, was helpful in establishing the diagnosis.
Unusual features of primary dermatofibrosarcoma protuberans and its myxoid recurrence
Authors: Betti Roberto , Inselvini Elena , Crosti Carlo
Published: April 2006

A case of Dermatofibrosarcoma Protuberans (DFSP) with unusual clinical and histological features is presented. The lesion recurred one year after surgical removal and showed myxoid degeneration of the entire lesion. Only a few cases with myxoid degeneration of the entire lesion are described in the literature. We found CD 34 stain, in combination with a panel of antibodies including fXIIIa, S100 and actin, useful in the diagnosis of this type of tumor in order to differentiate it from other neural, fibrous or muscular neoplasms.
An objective measurement of the anchoring strength of anagen hair in an adult with the loose anagen hair syndrome
Authors: Chapman David M. , Miller Robert A.
Published: April 2006

A 21‐year‐old male presented with the life‐long symptom of slowly growing, easily extractable hair lacking sheath remnants. The distribution and density of all his hair regions appeared normal and there was no alopecia. A hair‐pull test was painless and resulted in all hairs being removed, all in keeping with a diagnosis of loose anagen hair syndrome (LAHS). The trichogram was normal. Electronically measured epilation revealed values which were significantly lower than controls. His hair follicles were remarkable for this syndrome in that they looked perfectly normal with light microscopy; however, the segment of the follicle with the keratogenous zone was significantly shorter than normal. It is postulated that a subtle intercellular defect must reside in the line of shear proximal to the level of cuticular differentiation to account for the weak anchoring of the root in the follicle. A consequence of a genetic error probably causes both the weak anchoring and the slow hair growth.
The inhibitory effect of UVB irradiation on the expression of p53 and Ki‐67 proteins in arsenic‐induced Bowen's disease
Authors: Chai Chee‐Yin , Yu Hsin‐Su , Yen Huai‐Tzu , Tsai Kun‐Bow , Chen Gwu‐Shing , Yu Chia‐Li
Published: April 2006

The aim of this study is to evaluate the effect of ultraviolet B (UVB) on arsenic‐induced Bowen's disease. Four patients were irradiated with 750 mJ/cm2 of UVB and biopsies were performed before treatment and 2 weeks later. Immunohistochemical stains of p53 and Ki‐67 were compared by the labelled‐streptavidin method before and after the UVB treatment. We found that the number of p53 and Ki‐67 positive cells after the UVB treatment were significantly fewer than those of non‐UVB‐treated specimens. These results suggest that the UVB inhibitory effect in Bowen's disease needs further studies to clarify its value in potentially retarding the progression of the hyperproliferative status in overt skin cancer on a molecular basis.
Merkel cells are absent in basal cell carcinomas but frequently found in trichoblastomas. An immunohistochemical study
Authors: Schulz Tilman , Hartschuh Wolfgang
Published: April 2006

The possibility of a neuroendocrine differentiation in basal cell carcinomas (BCCs) has been a matter of debate for many years. In the present immunohistochemical study, applying the cytokeratins 8, 18 and 20 as the most established markers for Merkel cells (MCs), we did not find elevated numbers of MCs in any of 205 BCCs. This speaks against a neuroendocrine line of differentiation in BCCs. In contrast, we found various amounts of MCs in 15 of 36 trichoblastomas, which are the main benign differential diagnosis of BCC. In 4 trichoblastomas abundant MCs were spread over the whole epithelial tumor area. Additionally, the trichoblastomas' overlying epidermis exhibited significantly much higher numbers of MCs than the uninvolved adjacent skin or the epidermis overlying the BCCs. These findings might be an additional aid in the distinction between trichoblastomas and BCCs. Furthermore, concerning the recent discussion about the role of MC in growth and development of follicular germ, our observations are another sign of regulative influences of the MC, also in follicular germ under pathological conditions. Trichoblastomas with high numbers of MCs could be characterized as showing advanced differentiation toward the neuroendocrine component of the hair follicle, i.e. the MCs.
Histogenesis of clear cell hidradenoma: immunohistochemical study of keratin expression
Authors: Ohnishi T. , Watanabe S.
Published: April 2006

The expression of cytokeratins in 10 cases of clear cell hidradenoma, including 3 cases of solid cystic hidradenoma, were examined using 21 kinds of monoclonal antibodies. We divided them into three histologic patterns: massive nests with a few lumina (M nests), nests with some tubular lumina (L nests), and nests in solid cystic hidradenomas (S nests). All hidradenomas showed similar immunoreactivities to those in the lower dermal ducts or secretory cells of normal eccrine glands. With antibodies against simple epithelial cytokeratins (CKs 7, 8, 18, and 19), however, different immunostaining was noted among the three histologic patterns. Namely, the M nests failed to react to them, although some luminal cells in the L nests revealed a positive staining. Furthermore, a majority of luminal cells in the S nests revealed a positive staining with them. Therefore, we think that the luminal cells in solid cystic hidradenoma mainly differentiate toward the secretory cells, and that the M nests mainly differentiate toward the dermal duct. Those in the L nests are thought to differentiate toward the dermal duct and the secretory cells. The proportion of the differentiation toward luminal cells of dermal ducts to the differentiation toward secretory cells was the main difference among the three nests. In addition, there was no difference in immunophenotypes between clear cells and epidermoid cells in the two kinds of hidradenomas.
Detection of CD44 splice variants in formalin‐fixed, paraffin‐embedded specimens of human skin cancer
Authors: Dietrich A. , Tanczos E. , Vanscheidt W. , Schöpf E. , Simon J. C.
Published: April 2006

The standard form of CD44 (CD44s) and CD44 isoforms, containing sequences encoded by one or several of 10 different variant CD44 exons (v1‐v10), are thought to play a crucial role in the growth and metastasis of certain human tumors. Recently, monoclonal antibodies (mAbs) directed against all CD44 isoforms (panCD44), or against epitopes encoded by specific variant exons (CD44v) have been developed, which unfortunately only stain cryopreserved tissues. We wished to develop a technique to unmask chemically CD44s and CD44v epitopes in paraffin‐embedded specimens of human skin cancers, so that they would be accessible for these mAbs. To address this issue, CD44s and CD44v expression was compared in cryopreserved and in formalin‐fixed, paraffin‐embedded biopsies obtained from the same basal cell carcinomas (BCC), squamous cell carcinomas (SCC), primary malignant melanomas (PMM) and metastatic malignant melanomas (MMM). Formalin‐fixed tumors were de‐paraffinized and treated briefly with an antigen retrieval fluid (TUF™) at 95°C or left untreated. In untreated paraffin‐embedded tissues, no CD44s or CD44v staining was detected. In contrast, in antigen retrieval fluid‐treated biopsies CD44s and CD44v expression was identical to that in cryopreserved specimens of the same tumor with the exception of mAbs detecting v7/8 and v10. We conclude that antigen retrieval unmasks certain epitopes in formalin‐fixed, paraffin‐embedded tissues, thus facilitating future research on the relevance of CD44s and CD44v expression for human skin carcinogenesis.
Detection of human papillomavirus DNA in squamous cell carcinomas of a patient with mycosis fungoides: report of a case
Authors: Liranzo Maritza O. , Golitz Loren , Shroyer Kenneth R.
Published: April 2006

Human papillomaviruses (HPV) have been associated with squamous cell carcinomas (SCC) of the skin in both the immuno‐competent and the immunocompromised individual. A paucity of literature, however, exists concerning die presence of HPV in SCCs from patients with mycosis fungoides (MF)‐[cutaneous T‐cell lymphoma (CTCL)]. We describe a case of multiple SCCs in which HPV DNA was detected over a 9‐year period from a patient with MF. This patient with a long history of MF developed 7 small red scaly indurated lesions of sun and non‐sun‐exposed areas during a 9‐year period (1981–1989). Histologic examination of all the lesions revealed that they were SCCs. The patient had no recorded history of arsenic exposure. To investigate the possible role of HPV as a co‐carcinogen, we tested the 7 cases of SCC for HPV. Polymerase chain reaction (PCR) was performed on formalin‐fixed tissue sections using HPV L1 consensus sequence primers. Four of the 7 SCCs were positive for HPV DNA. These results suggest a possible role for HPV as a co‐carcinogen in the development of SCCs in this patient.
Adhesion molecule expression in normal skin and melanocytic lesions
Authors: Tronnier Michael , Alexander Martina , Wolff Helmut H.
Published: April 2006

Cell adhesion between surfaces of cells and to extracellular matrices represents a fundamental mechanism in tissue organization and influences the biological behaviour and the architecture of tumors. We investigated the expression of various adhesion molecules in normal skin (n=5), nevi (n=29), and malignant melanoma (n=10) by immunohistochemistry. Special attention was paid to the correlation between adhesion molecule expression and the respective architectural features, e.g. UV‐induced morphological changes, and the arrangement of melanocytes in congenital nevi. In nevi, a single erythemagenic close of UV‐light did not influence the influence expression of melanocytes, but results in an upregulation of α3β1‐ and α6β1‐integrin within the suprabasal layers of the epidermis. This suprabasal labelling was associated with an increased number of suprabasal melanocytes in UV‐irradiated nevi which were detected with HMB‐45 antibody. Nine of 10 congenital nevi demonstrated a labelling of α4β1‐integrin only in melanocytes of the deeper dermis. This integrin previously has been associated with high tumor thickness and the clinical outcome in melanomas. The integrin profile observed in melanomas differed in part from that seen in nevi with expression of β2‐and β3‐integrins in some cases. The results may indicate a correlation between adhesion molecule expression and histopathological findings in melanocytic lesions.
Cutaneous histopathology of Sézary syndrome: a study of 41 cases with a proven circulating T‐cell clone
Authors: Trotter M. J. , Whittaker S. J. , Orchard G. E. , Smith N. P.
Published: April 2006

Sézary syndrome is an uncommon variant of cutaneous T‐cell lymphoma (CTCL) characterized by erythroderma, pruritus, adenopathy, and circulating atypical T‐lymphocytes with cerebriform nuclei. The definition of Sézary syndrome can be further refined by including only patients with a circulating peripheral blood population of clonal T‐cells. We have evaluated 79 skin biopsies from such a group of 41 erythrodermic patients with circulating Sézary cells and a clonal population of T‐cells detected by T‐cell receptor‐figene rearrangement on Southern analysis of peripheral blood mononuclear cells. Histopathologic features consistent with chronic dermatitis were observed in 26/79 (33%) skin biopsy specimens, emphasizing that a non‐specific histologic appearance is common. Evidence of CTCL was lacking in 11/41 patients on biopsy of their erythrodermic skin. The survival of these patients was not significantly different from 30/41 patients in whom skin biopsies revealed changes diagnostic of CTCL, such as a dermal lymphocytic band with atypical lymphocytes (18/79, 23%) or a mycosis fungoides‐like infiltrate (30/79, 38%). This study confirms that non‐specific cutaneous hlstopathologic findings are common in Sézary syndrome, even when a circulating T‐cell clone is present. This stresses the need for peripheral blood genetic analysis and for multiple or repeat skin biopsies in erythrodermic patients when there is high clinical suspicion of CTCL.
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.
Search for Kaposi's sarcoma‐associated virus DNA in hemangioproliferative disorders and cutaneous malignant lymphoma
Authors: Serfling Ulrike , Lukowsky Ansgar , Audring Heike , Sterry W.
Published: April 2006

Recently, a Kaposi's sarcoma‐associated herpesvirus (KSHV) was discovered. We evaluated by PCR 14 paraffin‐embedded specimens with the histological diagnosis of endemic, classic and HFV‐associated Kaposi's sarcoma (KS) for the presence of the KSHV DNA sequence. In addition, biopsies of adjacent, histologically unaffected skin, peripheral‐blood mononuclear cells (PBMCs) of HIV‐infected KS patients, PBMCs of one classic KS patient, and specimens of patients with hemangioproliferative disorders other than KS as well as samples of cutaneous T‐and B‐cell lymphoma were analyzed for KSHV. In all cases of KS, independent of the KS subtype, KSHV was detected in lesional skin. No KSHV was found in biopsies of the adjacent unaffected skin or PBMCs of HFV‐infected KS patients. We found KSHV in the PBMCs of a patient with classical KS. All specimens of cutaneous T‐and B‐cell lymphomas or lymphomatoid papulosis were negative for KSHV. In addition, the samples with hemangioproliferative disorders other than KS were negative for KSHV. There was one borderline case of KS or acroangiodermatitis that was positive for KSHV. Additional histological sections and clinical evaluation confirmed the diagnosis of classic KS. In summary, the data indicate that PCR for KSHV should be a useful diagnostic tool in cases of hemangioproliferative disorders.
Less expression of cyclin E in cutaneous squamous cell carcinomas than in benign and premalignant keratinocytic lesions
Authors: Bito Toshinori , Ueda Masato , Ito Akiro , Ichihashi Masamitsu
Published: April 2006

In a previous study, we showed that overexpression of cyclin D, a G1 cyclin, is frequently associated with keratinocyte carcinogenesis as an early event. Another G1 cyclin, cyclin E, was recently suggested to be a prognostic marker for breast cancer. In order to evaluate the role of cyclin E in human keratinocyte carcinogenesis, we analysed the expression of cyclin E by immunohistochemistry in normal skin, seborrheic kaeratosis (SK), keratoacanthoma (KA), actinic keratosis (AK), Bowen's disease (BD), basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Positive cells were seen rarely in normal epidermis, in 9 of 20 cases of SK, in 5 of 6 cases of KA, in 9 of 13 cases of AK and in all 27 cases of BD. Some of the cases of AK and BD had positive cells in the superficial epidermis, where atypicality is less obvious. In contrast, positive cells were seen in 4 of 25 cases of SCC and none of 15 cases of BCC. These results suggest that expression of cyclin E plays a role in the formation of benign and premalignant keratinocytic tumors, whereas down‐regulation of cyclin E expression may be involved in carcinogenesis in human keratinocytes.
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.
Smooth‐muscle hamartoma of the tunica dartos of the scrotum: report of a case
Authors: Quinn Timothy R. , Young Robert H.
Published: April 2006

Hamartomatous proliferations of genital smooth muscle are uncommon and may be easily overlooked if the normal microscopic appearance of the scrotal dartos is unfamiliar to the pathologist. We describe a hamartomatous proliferation of the scrotum in a 60‐year‐old patient in which incomplete knowledge of the regional histology caused initial problems in diagnosis. On histologic examination, the lesion consisted of an expansile, unencapsulated, relatively circumscribed proliferation of smooth muscle accompanied by muscular arterioles and prominent nerve branches embedded in a densely collagenized stroma. These features are dissimilar both clinically and histologically from all previous reported lesions at this site. We highlight the histologic differences between our case and genital leiomyomas, and the spectrum of hamartomatous smooth‐muscle proliferations associated with a Becker nevus, and congenital and acquired smooth muscle hamartomas.
Differential proliferation of endothelial cells and keratinocytes in psoriasis and spongiotic dermatitis
Authors: Sweet William L , Smoller Bruce R.
Published: April 2006

This study used MIB‐1 monoclonal antibody to quantify the proliferating keratinocytes and endothelial cells and their proliferation fractions in cases of normal skin, acute and established plaque psoriasis, and acute and chronic spongiotic dermatitis. The number and the proliferation fraction of MIB‐1 positive cells were higher in psoriatic and chronic spongiotic lesions than in normal skin (p < 0.05). Established plaque psoriasis had a higher number of proliferating keratinocytes and a higher keratinocytic proliferation fraction than did acute psoriasis (p < 0.05). The number of proliferating endothelial cells decreased as acute psoriatic lesion became chronic, but the number in acute spongiotic lesion increased as it became chronic. The endothelial proliferation fraction was higher in acute psoriasis than in established plaque psoriasis (p < 0.05). The ratio of keratinocytic proliferation fraction to endothelial cell proliferation fraction of the psoriatic and spongiotic lesions suggested the presence of different reaction patterns to inflammation in psoriasis and spongiotic dermatitis.
Pleomorphic hyalinizing angiectatic tumor of soft parts: Immunohistochemical case study shows cellular composition by CD34+ fibroblasts and factor XIIIa+ dendrophages
Authors: Silverman Jeffrey S. , Dana Milton M.
Published: April 2006

We report immunomorphologic observations on a pleomorphic hyalinizing angiectatic tumor of soft parts (PHAT), a rare tumor recently described by Smith, Fisher, and Weiss. A 2 cm skin‐covered, grossly lobulated, firm, yellow‐tan, focally hemorrhagic tumor was excised from the dorsum of a 59‐year‐old woman's right foot. It infiltrated dermis and subcutis and entrapped skin adnexae. The tumor microscopically resembled both a pleomorphic malignant fibrous histiocytoma and a neurilemoma with fascicular spindle cell pattern, pleomorphic tumor giant cells, and focal congeries of ectatic, fibrinous, and slightly hyalinized vessels. Tumor cells produced abundant reticulin but collagenous sclerosis was minimal. Mast cells were numerous. Pleomorphic cells, some phagocytic, had intranuclear vacuolar inclusions and many cells had large pale cytoplasmic globular inclusions. Most tumor cells expressed vimentin and CD34, including pleomorphic cells. Factor XIIIa stained focally 20–40% of the spindle cells. S‐100 and cytokeratin were negative and actin and desmin stained only vessel myopericytes. The Ki 67 index was 3% with mostly large CD34+ cells and a few smaller FXIIIa+ cells in the cycling fraction. We conclude that PHAT is a fibrohistiocytic tumor probably derived from proliferating microvascular CD34+ dendritic cells and FXIIIa+ dendrophage cell subsets. Possible interactions between these cell types deserve further study in PHAT and other fibrohistiocytic tumors.
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.
Retiform hemangioendothelioma. A new case in a child with diffuse endovascular papillary endothelial proliferation
Authors: Sanz‐Trelles Andres , Rodrigo‐Fernandez Isabel , Ayala‐Carbonero Ana , Contreras‐Rubio Felix
Published: April 2006

We present a new case of retiform hemangioendothelioma (RH), an entity first described by Calonje et al. in 1994. The tumor was intradermal and located on the toe of an 11‐year‐old boy. Histologically, in addition to the distinctive retiform pattern of proliferating vessels in RH there are intraluminal papillae with hyaline cores similar to those seen in malignant endovascular papillary angioendothelioma (Dabska's tumor), but usually they are infrequent, focal and poorly developed. In our case, these papillary structures were well formed and distributed in a diffuse way. They were most conspicuous in superficial areas where the blood vessels were dilated. In deep areas, where the pattern of neoplastic vessels was retiform, the papillae filled their lumina totally, resembling solid cords. Our case shares the clinical and morphologic features of both retiform hemangioendothelioma and Dabska's tumor, supporting a relationship between these two kinds of neoplasms. The benign behavior of this case, with no recurrence or metastases over a 4‐year follow‐up, corresponds to the low malignancy of this kind of vascular neoplasm.
The t(2;5)‐;associated p80 NPM/ALK fusion protein in nodal and cutaneous CD30+ lymphoproliferative disorders
Authors: Su Lyndon D. , Schnitzer Bertram , Ross Charles W. , Vasef Mohammad , Mori Shigeo , Shiota Mami , Mason David Y. , Pulford Karen , Headington John T. , Singleton Timothy P.
Published: April 2006

A high percentage of extracutaneous CD30+ anaplastic large cell lymphomas (nodal ALCL) carry a specific chromosomal translocation, t(2;5) (p23;q35), that results in abnormal expression of p80 NPM/ALK chimeric protein (p80). The protein p80 may be detected by immunohistochemistry using polyclonal (anti‐p80) or monoclonal (ALK1) antibody directed against the ALK epitope. Although nodal ALCL, primary cutaneous ALCL, and lymphomatoid papulosis type A (lyp A) have similar histologic and immunohistochemical features, the expression of p80 in these cutaneous lesions has not been extensively studied. We immunostained tissues from 10 nodal ALCL, 8 primary cutaneous ALCL, 24 lyp A, and positive and negative controls using polyclonal rabbit anti‐p80 and the avidin‐biotin‐peroxidase labeling method. Reactivity was determined by comparing staining intensity to positive controls [4 nodal ALCL with t(2;5)] and negative controls (21 non‐ALCL lymphomas). Only cutaneous lesions staining positively with anti‐p80 were further studied with the monoclonal antibody ALK1 and reverse transcription polymerase chain reaction (RT‐PCR) for p80 messenger RNA. All positive controls (4/4), but none of the negative controls (0/21) nor lyp A (0/24), were immunoreactive for anti‐p80. Sixty percent (6/10) of nodal ALCL and a single case (12%) of primary cutaneous ALCL were immunoreactive for anti‐p80. In this exceptional cutaneous lesion, although we did not find NPM/ALK by RT‐PCR, we detected strong expression of ALK using ALK1. We conclude that t(2;5) is rarely involved in the pathogenesis of cutaneous CD30+ lymphoproliferative disorders.
Cutaneous histopathology of Rocky Mountain spotted fever
Authors: Kao Grace F. , Evancho Charles D. , Ioffe Olga , Lowitt Mark H. , Dumler J. Stephen
Published: April 2006

The dermatologic diagnosis of Rocky Mountain spotted fever (RMSF) is often presumptive; the clinical presentation includes skin rash and febrile illness with or without a clear history of tick bite. The characteristic cutaneous manifestations include a generalized skin eruption with purpuric, blanching or non‐blanching macules and papules usually involving the extremities. Although skin biopsies are often performed to confirm the diagnosis, the spectrum of cutaneous histopathology in RMSF has not been well described. We studied a series of 26 cases of RMSF, of which 10 were surgical specimens and 16 were autopsies. The microscopic changes were correlated with the duration of illness. The main histopathologic feature was lymphohistiocytic capillaritis and venulitis with extravasation of erythrocytes, edema, predominantly perivascular and some interstitial infiltrate. Leukocytoclastic vasculitis (LCV) with neutrophilic infiltrate and nuclear dust was seen in 11 of 15 (73%) specimens from involved skin. These lesions with LCV also showed notable epidermal change including basal layer vacuolar degeneration with mild dermoepidermal interface lymphocytic exocytosis. Six lesions with LCV displayed focal fibrin thrombi and capillary wall necrosis. Apoptotic keratinocytes were noted in 3 lesions with LCV. Subepidermal blister was observed in the skin lesion of an autopsied patient with LCV changes. Another lesion of a fetal case with LCV also contained features of acute neutrophilic eccrine hidradenitis. Focal small nerve twig inflammation was noted in a third autopsy case with LCV. Plasma cells were seen in 6 of 34 specimens (18%); and eosinophils were observed in 3 (9%). The subcutaneous fat contained a mild perivascular inflammation and one case revealed focal lobular neutrophilic inflammation. Immunohistologic (IH) staining using polyclonal rabbit anti‐Rickettsia rickettsii demonstrated positive staining of the organisms in the affected endothelial cells in all 12 cases tested. The cutaneous histopathology of RMSF is caused by endothelial damage by the rickettsial organisms which elicit an initial lymphohistiocytic small vessel vasculitis with progression to LCV. The vasculitis in RMSF is, therefore, considered to be a form of septic vasculitis.