bluuebunny/crossref_metadata_2025 huggingface dataset:
Myoid differentiation in dermatofibrosarcoma protuberans and its fibrosarcomatous variant: clinicopathologic analysis of 5 cases
Authors: Calonje Eduardo , Fletcher Christopher D.M.
Published: April 2006

We report a series of five cases of dermatofibrosarcoma protuberans, four of which were fibrosarcomatous and all of which showed histologic and immunohistochemical evidence of focal myoid/myofibroblastic differentiation (accounting for up to 5% of each tumor). These lesions were identified amongst 208 cases of dermatofibrosarcoma protuberans including 24 examples of the fibrosarcomatous variant. Three of the five patients were male and two were females; all were adults (37–72 years). One case arose on the scalp and two cases each on the abdominal wall and upper trunk. All tumors were less than 5cm in diameter and preoperative duration ranged from 2 months to 10 years. In three cases with follow‐up there was no recurrence. Histologically, all tumors were typical fibrosarcomatous or ordinary dermatofibrosarcoma protuberans but for the presence of scattered to confluent nodules and bundles of eosinophilic spindle cells associated with well‐defined cytoplasmic margins and vesicular nuclei associated with focal stromal hyalinization. While the typical dermatofibrosarcoma protuberans areas were CD34 positive, the myoid areas were negative for this antibody and positive for smooth muscle actin and pan‐muscle actin. All tumors were desmin negative. Recognition of myofibroblastic differentiation in fibrosarcomatous dermatofibrosarcoma protuberans is important not only because it gives support to the theory of a fibroblastic/myofibroblastic line of differentiation for this type of tumor, but also because it might be a source of confusion with other myofibroblastic lesions (e.g. myofibromatosis, adult myofibroma), especially when small biopsies are evaluated.
Elastic fibers in scar tissue
Authors: Roten Sonja Vollenweider , Bhat Shailesh , Bhawan Jag
Published: April 2006

The capacity of the skin to be stretched and to return to its resting position is correlated to the quantity and to the quality of the elastic fiber network. Although elastic fibers have been demonstrated in scars, the time course of their appearance in scars and their role in scar elasticity has not been elucidated. A study was therefore undertaken to evaluate the elastic fiber network in scars.

The scars studied were from re‐excision specimens following a biopsy performed for a benign or a malignant process. A total of 182 scars were evaluated in patients of different age groups. Miller's elastic tissue stain, considered to be superior to Verhoeff's van Giesen stain, was used. No elastic fibers were detected in any of 116 scars which were of less than 3 months' duration. In 66 scars present for over 3 months, a progressive increase in elastic fibers was present, first as focal and thin fibers, then as diffuse and thicker fibers. For scars of the same duration, a regional difference was noted in that scars from the back contained more and thicker elastic fibers than those from the cheek. When patients were stratified according to age, no appreciable difference was noted in the density of elastic fibers in both new and old scars between the different age groups. These results show that the synthesis of elastic tissue fibers in scars is a function of duration and site of the scar.
T‐cell‐rich B‐cell lymphoma presenting in skin
Authors: Sander Christian A. , Kaudewitz Peter , Kutzner Heinz , Simon Martin , Schirren Carl Georg , Sioutos Nicholas , Cossman Jeffrey , Plewig Gerd , Kind Peter , Jaffe Elaine S.
Published: April 2006

We reviewed our experience with six T‐cell‐rich B‐cell lymphomas (TRBL) presenting in skin. Immunohistochemical studies were performed on all biopsies. The lymphoid population consisted mainly of CDS and/or UCHL‐1 (CD45RO) positive T cells. 5 to 15% of the lymphoid cells stained for the B‐cell marker L26 (CD20). Monoclonality of the B‐cell component was demonstrated in all cases, utilizing either light chain restriction (5 cases) or clonal immunoglobulin heavy chain gene rearrangement by polymerase chain reaction (PCR) (2 cases). One case was confirmed to be monoclonal by both techniques. Additionally, no clonal rearrangements of the T‐cell receptor gamma gene were observed. There was considerable morphological variety in these cases. In H&E stained sections, the differential diagnosis included pseudolymphoma, peripheral T‐cell lymphoma, Hodgkin's disease, Lennert's lymphoma and a MALT lymphoma. A significant component of monoclonal plasma cells was present in 3 of 6 cases, suggesting a possible origin from cutaneous immunocytoma. In fact, one of our cases was a biphasic lymphoma displaying TRBL with a small focus of immunocytoma. We conclude that immunophenotypic analysis is necessary for the diagnosis of TRBL. Pathologists should be aware of this type of cutaneous B‐cell lymphoma to avoid misinterpretation as a pseudolymphoma.
Small‐diameter invasive melanomas: clinical and pathologic characteristics
Authors: Gonzalez Alfonso , West Andrew J. , Pitha Jan V. , Taira James W.
Published: April 2006

Background: Most melanomas when first diagnosed clinically are larger than common benign melanocytic nevi (> 6 mm). Smaller melanomas, however, may occasionally occur. Yet, very little is known about them.

Objective: To determine the incidence and delineate the clinical and histologic characteristics of small‐diameter invasive melanomas.

Methods: Slides of all melanomas diagnosed between 1984–1993 were reviewed and measured. All invasive lesions less than 6 mm were further scrutinized clinically and morphologically. Results: Among 357 invasive melanomas, 16 (4.4%) were less than 6 mm. Most lesions lacked some of the histologic features usually seen in large melanomas. One half of them were over 0.75 mm deep. Patients with small melanomas were on average 15 years younger than those with large lesions. In females, sites on the upper extremities predominate. In females, small melanomas had clinical signs of melanoma, while in males they resembled nevi.

Conclusion: Melanomas smaller than 6 mm are not rare. Clinicians and pathologists must learn their features in order to diagnose them properly.
CD44 and melanocytic tumors: a possible role for standard CD44 in the epidermotropic spread of melanoma
Authors: Fernández‐Figueras Maria‐Teresa , Ariza Aurelio , Calatrava Ana , Puig Lluis , Fernández‐Vasalo Angeles , Ferrándiz Carlos
Published: April 2006

CD44 is a polymorphic family of cell membrane glycoproteins that mediate cell‐matrix and cell‐cell interactions involved in the mechanisms of tumor invasion and metastasis, and are subject to differential regulation during normal and malignant cell growth. We have investigated immunohistochemically the expression of CD44S and the variant isoforms CD44v3 and CD44v6 in paraffin‐embedded tissue from 5 Spitz nevi, 3 compound melanocytic nevi, 2 blue nevi, 6 primary melanomas, 15 cutaneous metastases (three epidermotropic, nine dermal and three ulcerated) and 10 lymph node metastases of melanoma. Melanocytes were extensively positive for CD44S in primary melanomas and benign melanocytic proliferations. Among 15 cases of cutaneous metastases of melanoma, the three epidermotropic metastases, as well as one of the three ulcerated ones were positive for CD44S. CD44S expression was diminished or totally absent in six of the nine dermal metastases, in two of the ulcerated metastases and in seven of the ten lymph node metastases. CD44v3 and CD44v6 melanocytic expression was absent in all the lesions studied.

According to our results, selective retention of CD44S expression by melanocytes in epidermotropic metastases of melanoma seems to indicate that preservation of CD44S may contribute to the intraepidermal spread of melanoma.
Sudoriferous acrosyringeal acantholytic disease
Authors: Hashimoto Ken , Moiin Ali , Wu Chang Mary , Tada Joji
Published: April 2006

Three selected cases of transient acantholytic dermatosis were studied because of their definitive correlation with sweating due to fever and/or bed‐ridden situations. Biopsy specimens were serially sectioned and acantholysis was found in the acrosyringium or traced to connect to the acrosyringium in all biopsy specimens. Carcinoembryonic antigen (CEA) and eccrine gland‐specific monoclonal antibody, IKH‐4, were positive in acantholytic cells. Electron microscopy revealed electron dense material filling the lumen of intraepidermal eccrine ducts. This material leaked into lateral intercellular spaces of the luminal cells, passing tight junctions. Marked edema and numerous lysosomes were reminiscent of those found when eccrine acrosyringium is formed in the embryo; this suggested that an occluded and damaged eccrine intraepidermal duct was being rebuilt via lysosomal digestion.
Sjögren's syndrome plasma cell panniculitis and hidradenitis
Authors: McGovern Thomas W. , Erickson Alan R. , Fitzpatrick James E.
Published: April 2006

We present a 42‐year‐old woman with primary Sjögren's syndrome and a polyclonal gammopathy who presented with pre‐tibial petechiae, purpura, and tender indurated plaques. The indurated plaques revealed a lobular plasma cell panniculitis, and thus Sjögren's syndrome should be added to the short list of collagen vascular diseases that can present as plasma cell panniculitis. Her biopsies also demonstrated intense perieccrine plasma cell infiltrates that may account for Sjögren's syndrome‐associated hypohidrosis. We also observed occasional vascular occlusion of vessels with an amorphous, eosinophilic material possibly related to her hypergammaglobulinemic purpura.
Cutaneous lymphangiectases associated with severe photoaging and topical corticosteroid application
Authors: Pena Julie M. , Ford Michael J.
Published: April 2006

We report an elderly patient with lymphangiectases arising within skin affected by photoaging, steroid atrophy, and inflammation. Bullous lesions appeared in several sites following a year of topical corticosteroid applications for neurodermatitis. Light and electron microscopy showed that the bullae consisted of dilated lymphatic vessels within the dermis. There was also marked nodular elastosis and attenuation of dermal collagen. We suggest that this patient's lymphangiectases resulted from abnormal structure and function of the dermis due to photoaging and steroid atrophy.
Persistent cutaneous pseudolymphoma after intradermal gold injection
Authors: Kalimo Kirsti , Räsänen Liisa , Aho Heikki , Mäki Jouko , Mustikkamäki Urho Pekka , Rantala Immo
Published: April 2006

After intradermal testing with goldsodiumthiomalate (GSTM), 5 out of 8 patients developed skin papules at the test sites, which persisted up to 20 months. The lesions were surgically excised. Histology revealed pseudolymphoma of B and T cell type containing follicular structures and occasional small granulomas. The amount of histiocytic cells among B and T lymphocytes was pronounced, including acid cysteine proteinase inhibitor (ACPI) positive follicular dendritic cells, CD68 positive macrophages, factor XUIa positive dermal dendrocytes and S‐100 positive cells. By electron microscopy, the macrophages contained endosomes loaded with crystalloid material which contained gold in X‐ray microanalysis. Atomic absorption spectrophotometry also confirmed the presence of gold in one specimen. Thus GSTM seemed to accumulate in tissue macrophages leading to constant immunologic activation with lymphoid proliferation and histiocytic response.
Extra‐acral calcifying aponeurotic fibroma: a distinctive case with 23‐year follow‐up
Authors: Murphy Bettina A. , Kilpatrick Scott E. , Panella Mike J. , White Wain L
Published: April 2006

Calcifying aponeurotic fibroma (CAP) is an unusual but well‐characterized soft tissue neoplasm that typically involves the digits of children and frequently recurs locally. This report describes a case from the subcutis of the lumbosacral region. A 26‐year‐old man initially presented at age 3 and developed three recurrences over a 23‐year period each at approximately 8‐year intervals (ages 10, 18, and 26). The microscopic findings in all recurrences showed a lobulated, poorly circumscribed proliferation of dense fibrous tissue containing epithelioid‐like fibro‐blasts, multinucleated cells, and islands of metaplastic chon‐droid differentiation with focal calcification. Despite origin from an unusual anatomic site, this case reported herein demonstrates the classical morphologic features and clinical history of CAT which showed little in the way of morphologic evolution despite 23 years of persistence. The clinical and histologic features helpful in distinguishing CAP from infantile fibromatosis and soft tissue chondroma are discussed.
Ossifying fibromyxoid tumor of soft parts of the back
Authors: Nakayama Fumiaki , Kuwahara Takeichirou
Published: April 2006

We report a first case of ossifying fibromyxoid tumor of soft parts of the back, a 10×9.5×6 cm well‐circumscribed elevated subcutaneous tumor demarcated by an incomplete fibrous capsule with bone formation at its base. The tumor was composed of both myxomatous areas with spindle tumor cells and pseudoalveolar structures with oval tumor cells. The tumor cells had evenly sized, oval nuclei without atypia and slightly eosinophilic cytoplasm with intracellular vacuoles. Immunohistochemical studies revealed positivity for vimentin and focal positivity for S‐100 protein. Ultrastructural examination revealed a few filopodia‐like processes, discontinuous basal lamina and a few primitive cell junctions. Based on these immunohistochemical and ultrastructural results, this tumor may be related to Schwann's cells. There has been no recurrence 5 years after wide local excision.
Cellular actions of etretinate in psoriasis: enhanced epidermal differentiation and reduced cell‐mediated inflammation are unexpected outcomes
Authors: Gottlieb Scott L. , Hayes Elizabeth , Gilleaudeau Patricia , Cardinale Irma , Gottlieb Alice B. , Krueger James G.
Published: April 2006

Retinoids are potent cell growth and differentiation modulators, but cellular effects of therapeutic retinoids in psoriasis are unknown. We studied the effects of etretinate on pathological activation of keratinocytes and lymphocytes in patients treated systemically with this agent for 8 weeks. Ten patients with extensive psoriasis vulgaris were treated with etretinate at 0.75 mg/kg for 8 weeks. Skin biopsies obtained before and at 8 weeks of treatment were studied using immunohistochemical markers for keratinocyte proliferation or differentiation and for the presence of T‐lymphocyte subsets or associated inflammatory proteins. During 8 weeks of treatment, the clinical severity decreased by a mean of 64% (p < 0.001). Compared to a similar group of patients treated with bath PUVA, psoriatic plaque erythema resolved more slowly and less completely (p < 0.05), but improvements in plaque thickness and scale were not significantly different between etretinate and PUVA treatments. Etretinate produced a 44% decrease in epidermal thickness (p < 0.001) and a 62% reduction in keratinocyte proliferation (p < 0.001) after 8 weeks of treatment. Unexpectedly, keratinocyte differentiation was enhanced following etretinate treatment as indicated by increased filaggrin production, increased number and size of keratohyaline granules, greater abundance of keratin filaments, and increased secretion of intercellular lipids from Odland bodies. The stratum corneum in resolving psoriatic lesions was unusually thin, probably caused by retinoid‐induced shedding of corneocytes. “Regenerative” epidermal growth was maintained during etretinate treatment, as marked by continued expression of keratin 16 and a3‐integrin by suprabasal keratinocytes. Surprisingly, the inflammation‐associated proteins HLA‐DR and ICAM‐1 were no longer produced by epidermal keratinocytes following etretinate treatment, and CD3+, CD8+, and CD25+ T‐lymphocyte subsets were reduced by 50‐65% in lesional tissue (p < 0.01). Etretinate shows unexpected anti‐inflammatory and pro‐differentiation actions in psoriasis. Etretinate appears to function as a disease suppressive agent which improves hyperplasia, keratinocyte differentiation and tissue inflammation mediated by cellular immune elements.
Intradermal and subcutaneous leiomyosarcoma: a clinicopathological and immunohistochemical study of 41 cases
Authors: Jensen Marianne Lidang , Jensen Olaf Myhre , Michalski Wojchiech , Nielsen Ole Steen , Keller Johnny
Published: April 2006

Superficial leiomyosarcomas are rare tumours. The lesions confined to the dermis, contrary to those involving the subcutis, have been reported to carry a favourable prognosis.

A retrospective study of 41 consecutive cases of surgically treated intradermal and subcutaneous leiomyosarcomas was undertaken in order to determine the prognostic factors that may influence the survival of these patients. Seven tumours were predominantly intradermal and 34 involved the subcutaneous tissue. Fifty‐four percent of the tumours were located in the lower extremities. All cases stained positively for smooth muscle antigen and 66% for desmin. The tumours were classified with regard to tumour grade I (low grade, 3%), II (intermediate, 12%), IIIA (high grade, 46%) and IIIB (high grade, 39%). In all patients, follow‐up information was available. Mean follow‐up time was 5 years. The patients with intradermal tumours were all alive without signs of recurrence, whereas 14 of those with leiomyosarcomas involving the subcutis have died with pulmonary metastases.

Our study confirms that “pure” intradermal leiomyosarcomas independent of tumour grade behave in a benign fashion, probably due to small tumour size. Tumour size ≥ 5 cm, deep localization with fascia involvement, and high malignancy grade (IIIB) were found to deteriorate survival based on a univariate analysis. However, in a multivariate analysis only tumour size was found to be an independent prognostic factor.
Macrophages and vascular adhesion molecules in oral Kaposi's sarcoma
Authors: MacPhail Laurie A. , Dekker Nusi P. , Regezi Joseph A.
Published: April 2006

Kaposi's sarcoma (KS) is a heterogeneous tumor where spindle cells are predominant and macrophages and factor XIIIa positive dendrocytes are abundant. The origin of the macrophages and dendrocytes is unclear, although their numbers suggest a critical role in KS pathogenesis. To determine if KS macrophages are recruited from the blood stream or proliferate on‐site, we examined biopsy specimens 1) for expression and distribution of vascular adhesion molecules (PECAM‐1, ELAM‐1, ICAM‐1, VCAM‐1, P‐selectin, L‐selectin) and the macrophage‐associated adhesion‐molecule ligand, VLA‐4; 2) for dual expression of proliferation (Ki‐67) and lineage‐associated markers (KP‐1, CD34, factor XIIIa, LCA); and 3) for dual expression of macrophage (KP‐1) and endothelial cell (CD34) associated markers. Avidin‐biotin peroxidase techniques were used. Resident vessels were found to strongly express PECAM‐1, ELAM‐1, ICAM‐1, P‐selectin, and moderately express VCAM‐1 and VLA‐4. Tumor spindle cells showed less intense expression of ELAM‐1, ICAM‐1 and P‐selectin. The most frequent double‐stain combination was Ki‐67+CD34‐K In contrast, the combinations of Ki‐67+KP‐l+, Ki‐67+XIIIa+ and KJ‐67+LCA+ were rarely seen. The enhanced expression of adhesion molecules on resident vessels and the lack of evidence of macrophage proliferation suggest that the abundant macrophages in KS are recruited from the blood stream.
Altered expression of epithelial integrins and extracellular matrix receptors in oral erythema multiforme
Authors: Mirowsk Ginat W. , Lozada‐Nur Francina , Dekker Nusi P. , MacPhail Laurie A. , Regezi Joseph A.
Published: April 2006

Inflammation and ulceration at the epithelium‐connective tissue interlace, a characteristic of erythema multiforme (EM), may be associated with altered molecular attachment of basal keratinocytes. To determine the expression of basal keratinocyte‐associated integrins and their basement membrane ligands in oral EM, specimens of clinically and microscopically confirmed EM (n=12) and mucosal controls (n=7) were stained immunohistochemically for the integrins α3, β6, β1, and β4 and for extracellular matrix proteins laminin 1, laminin 5, collagen IV, and collagen VII using a standard avidin‐biotin‐peroxidase technique. In EM, results showed increased staining intensity for all integrins studied in basal and suprabasal keratinocytes. Basement membrane‐associated staining of a6 and b4 was intense, but disrupted and fragmented. In EM, integrin staining was most marked at the summit of the connective tissue papillae. Laminin 5 staining was more intense than in controls, was frequently fragmented, and extended into the lamina propria. Laminin 1 staining was discontinuous and was frequently less intense than in controls. Collagen IV staining in EM was interrupted along the basement membrane. Collagen VII staining was fragmented but unchanged in intensity. These alterations in interface adhesion molecules suggest that hemidesmosome‐associated molecules are important in the pathogenesis of EM. The staining intensities and patterns of expression of these adhesion molecules suggest that oral EM is initially focused in the connective tissue papillae.
Bowenoid epidermotropic metastatic squamous cell carcinoma
Authors: Ihm Chull‐Wan , Park Soo‐Lieon , Sung So‐Young , Lee In‐Seob
Published: April 2006

Epidermotropic metastatic squamous cell carcinoma produced full‐thickness cellular atypia of bowenoid carcinoma in situ or vulvar intraepithelial neoplasia, grade 3 (VIN 3), in a 73‐year‐old woman who had past history of uterine cervical carcinoma. The presence of intravascular tumor cell nests and areas showing smooth continuity of the malignant squamous cell nodules with the adjoining benign epidermis supported the possibility of the epidermotropic metastasis. To our knowledge, metastatic epidermotropic squamous carcinoma clinicopathologically simulating primary Bowen's disease has not been reported.
Curvicircular intracytoplasmic membranous structures in keratinocytes of pemphigus foliaceus
Authors: Tada Joji , Hashimoto Ken
Published: April 2006

We noticed intracytoplasmic membranous, annular, or circular structures in the lesion of pemphigus foliaceus and studied these by regular transmission electron microscopy and immuno‐electron microscopy. These curvicircular bodies were observed in the preacantholytic keratinocytes of the blister wall as well as in acantholytic cells in 6 out of 6 patients with pemphigus foliaceus. They were absent in samples from 3 patients with pemphigus vulgaris. These structures were about 60–70 nm wide and consisted of 4 electron‐dense layers. They were continuous with intact desmosomal structures and gap junctions in the periphery of the keratinocytes. These curvicircular membranous bodies were well labeled with immunogold particles for desmoglein, plakoglobin, connexin 43, and IgG. In contrast to pemphigus vulgaris, splitting of desmosomes through dissolution of intercellular desmoglea was seldom observed in all 6 specimens of pemphigus foliaceus. These findings suggest that in pemphigus foliaceus 1) curvicircular bodies are derived from internalized desmosomes and gap junctions, and 2) cell‐to‐cell adhesions are weakened by this internalization and acantholysis is initiated, while in pemphigus vulgaris the dissolution of clesmoglea is the initial event. It is suggested that in pemphigus foliaceus the binding of autoantibody induces internalization of many intact desmosomes and gap junctions rather than splitting them.
Chondroid syringoma: an immunohistochemical study using antibodies to Ca 15‐3, KA‐93, Ca 19‐9, CD44 and BM‐1
Authors: Tsuji Takuo
Published: April 2006

The expression of Ca 15‐3, KA‐93, Ca 19‐9, CD44 and BM‐1 in normal skin and chondroid syringoma was investigated immunohistochemically using antibodies to these antigens.

In the normal skin, the eccrine ducts and/or secretory elements were positive for all these antigens. On the other hand, the apocrine ducts and/or secretory elements were positive for the antibodies to Ca 15‐3, KA‐93 and CD44.

In chondroid syringoma, the luminal cells of tubnloglandular structures were positive for the antibodies to Ca 15‐3 and BM‐1, and partly positive for those to KA‐93 and Ca 19‐9. The basal cells of the tubular structures and solid nests were positive only for the antibody to CD44. Stromal cells in the myxoid area were positive for the antibodies to KA‐93 and CD44, and the chondroid matrix was positive for the antibody to BM‐1.

It is suggested that chondroid syringoma might originate from, or differentiate into the ducts and/or secretory elements of the eccrine sweat glands. In addition, the significance of the expression of BM‐1 in the chondroid matrix is discussed.
Malignant eccrine poroma with multiple visceral metastases: report of a case with autopsy findings
Authors: Maeda Tamaki , Mori Hiroshi , Matsuo Takahira , Nakagawa Jun‐ichi , Yamauchi Hiroaki , Tuziguchi Hitomi , Hongou Yasusi
Published: April 2006

An autopsy case of malignant eccrine poroma (MEP) with multiple visceral metastases is reported. A flat, dark tumor of 1 cm in diameter developed on a pre‐existing pigmented spot at the left side of the waist of a 58‐year‐old male. The histopathology suggested the tumor to be malignant melanoma. Nine years later, a painless swelling occurred in the left lower leg, resulting from the obstruction of lymphatics at the left inguinal region. The swelling continued and spread with pain, reaching the inguinal region. Two years later, several papules appeared around the left knee, from which an extensive lymphorrhea occurred. The histopathology of the resected papules suggested epidermoid carcinoma or trichilemmal carcinoma, mainly localized within the lymphatics of the upper dermis. Re‐examination of the first skin tumor and electron microscopy of the tumor obtained at autopsy revealed that both tumors were MEP. Although the metastases to the local cutaneous regions and lymph nodes via the lymphatics occur in 20% of MEP, cases with multiple visceral metastases are very few.
Clinical and histological features of poor prognosis in cutaneous metastatic melanomas
Authors: Hofmann‐Wellenhof R. , Woltsche‐Kahr I. , Smolle J. , Kerl H.
Published: April 2006

Patients with melanoma metastatic to the skin show variable prognosis. Though some may survive for quite a long time, some die of disseminated disease within 1 year of removal of cutaneous metastases. The aim of this study was to find out whether there are any histological criteria indicating particular poor outcome. Clinical and histological features of 344 melanoma lesions metastatic to the skin were assessed and their prognostic relevance was investigated. H&E stained histological slides were scanned for the presence of morphological criteria expressing certain tumor cell ‐ stroma interactions: capsule formation (CAPSULE), formation of intratumoral septa (NEWSEPTA), simple invasion between collagen of reticular dermis (DERM‐SIMPLE), or subcutis (SCSIMPLE), preservation of preexistent collagen (PRECOLL) or fatty tissue (PREFAT) and, finally, histological site of metastasis. Additionally, anatomical location of the metastases, time between removal of primary tumor and metastases, age and sex of patients were recorded. The metastases were divided into two groups: lesions of patients who died within 1 year after resection (n=59) and lesions from patients with a longer survival (n=285).

Metastases which were associated with death within one year were significantly more often found in male patients (54.2% versus 34.7%), in younger patients (mean age 51.1±14.1 years versus 58.8 ± 15.3 years), had developed earlier after the primary tumor (mean time of 21.7±19.9 months versus 43.3±27.4 months) and were more often found at distant sites than in localregional sites (45.7% versus 30.5%), and were more often involved in the subcutis (74.5% versus 56.1%). From a histological point of view, DERMSIMPLE (80% versus 46%; p<0.001) and PRECOLL (82.8% versus 57.6; p<0.01) were more frequent in metastases of poor outcome. The same was true for SCSIMPLE (50% versus 25.6%; p<0.01) and PREFAT (68.1% versus 46.8%; p<0.05) in lesion with subcutaneous growth, whereas CAPSULE (54.5% versus 75%) was less frequently seen.

In conclusion, melanoma deposits metastatic to the skin with particular poor outcome differ clinically and histologically from other cutaneous melanoma metastases. This should be taken into account in the design of therapeutic clinical trials.
Intermediate‐ and low‐molecular‐weight keratin detection with the monoclonal antibody MNF116. An immunohistochemical study on 232 paraffin‐embedded cutaneous lesions
Authors: Prieto Victor G. , Lugo Jorge , McNutt N. Scott
Published: April 2006

Immunohistochemical detection of certain low to intermediate molecular weight keratins often is impaired in routinely processed specimens due to masking of these antigens by formalin fixation. Despite standard enzymatic digestion, AE1:AE3 and CAM 5.2, two of the most currently utilized antikeratin antibody preparations, either stain weakly or fail to stain basal keratinocytes and tumors composed of basaloid keratinocytes in paraffin sections of formalin‐fixed tissue.

We present here our experience with the monoclonal antibody MNF116 which detects keratins 5, 6, 8, 17, and 19 (DAKO, Carpinteria, CA). We have studied 232 routinely‐processed skin lesions with MNF116 and compared the staining with that of AE1:AE3 mixture or CAM 5.2. In normal skin, the staining achieved with MNF116 was particularly strong on the basal cells of the epidermis and adnexae. MNF116 was positive in all 154 epithelial tumors and negative in all but one (a leiomyosarcoma) of 78 mesenchymal and melanocytic tumors. AE1:AE3 mixture was positive in all but four poorly‐differentiated squamous cell carcinomas and it was only weakly positive in most basal cell carcinomas. CAM 5.2 was positive in tumors of the sweat apparatus, Merkel cell carcinomas, metastatic carcinomas, and 5/15 basal cell carcinomas.

We consider that, in routinely processed specimens, MNF116 is very useful and convenient for detection of cytokeratin expression in cutaneous lesions, and therefore helpful in the evaluation of tumors with small cells and other poorly differentiated neoplasms of the skin.
Systemic cytokine administration alters the histology of the eruption of lymphocyte recovery
Authors: Horn Thomas , Lehmkuhle Mary Ann , Gore Steven , Hood Antoinette , Burke Philip
Published: April 2006

The eruption of lymphocyte recovery occurs after marrow ablative antineoplastic chemotherapy, with the earliest reappearance of lymphocytes in the peripheral circulation. The typical histopathologic findings are not specific, consisting of a perivascular lymphocytic infiltrate in the upper dermis with mild overlying epidermal changes. Since the initial report, 21 additional biopsy specimens from eruptions of lymphocyte recovery were obtained at our institution. Of these specimens, 18 displayed the expected findings while 3 specimens contained a relatively heavy lymphocytic infiltrate with nuclear pleomorphism and hyperchromasia. The majority of lymphocytes from the heavily inflamed tissues expressed CD3 and CD4; rare CD8+ cells were observed. The cells with large irregular nuclear contours displayed an “activated” phenotype, consisting of CD30, HLA‐DR, and CD25, accounting for roughly 50% of the total infiltrate. The three patients from whom these specimens were obtained had received human recombinant cytokines in pharmacologic doses (2 granulocyte‐macrophage colony stimulating factor, 1 inter‐leukin‐3). Three patients in this series also received human recombinant cytokines, but developed eruptions with the typical scant infiltrate of small lymphocytes. These findings extend the histologic spectrum of the eruption of lymphocyte recovery and suggest that the administration of human recombinant cytokines prior to marrow recovery may alter the appearance and phenotype of lymphocytes migrating into the skin.
Neutrophilic spongiosis in pemphigus herpetiformis
Authors: Huhn Karen M. , Tron Victor A. , Nguyen Nhiem , Trotter Martin J.
Published: April 2006

Pemphigus herpetiformis is a rare pemphigus variant with light microscopic features that have historically been described as either “acantholytic dermatitis herpetiformis” or as “eosinophilic spongiosis in pemphigus”. The clinical features of this form of pemphigus are reminiscent of dermatitis herpetiformis; however, the direct immunofluorescence finding of epidermal intercellular IgG deposition is that of the pemphigus group. We report two patients with clinical presentations suggestive of dermatitis herpetiformis in whom the histopathologic features were those of a neutrophilic intraepidermal blistering disorder. Biopsies showed marked epidermal spongiosis with midepidermal acantholytic vesicles containing predominantly neutrophils and a few eosinophils. Direct immunofluorescence was positive for epidermal intercellular IgG; IgA deposition was not present. Neutrophilic spongiosis, in the absence of a prominent eosinophilic infiltrate, should be recognized as an early finding in some cases of pemphigus, and immunofluorescence studies are justified when this histologic feature is encountered in a skin biopsy.
Histiocytic sarcoma that mimicks benign histiocytosis
Authors: Boisseau‐Garsaud Anne‐Marie , Vergier Béatrice , Beylot‐Barry Marie , Nastasel‐Menini Florentina , Dubus Pierre , de Mascarel Antoine , Eghbali Houchingue , Beylot Claire
Published: April 2006

A 28‐year‐old man presented with a histiocytic sarcoma of a very uncommon origin, as it had developed for several years like a benign cutaneous histiocytosis resembling generalized eruptive histiocytoma before becoming acute, with nodal and massive pulmonary involvement. Despite various chemotherapies, the patient died within 8 months. Skin biopsies showed histiocytic proliferation in the dermis and node biopsies showed histiocytic proliferation with a sinusoidal pattern. Immunohistochemical analysis, performed on paraffin‐embedded sections, demonstrated strong labeling of tumoral cells for CD68 and moderate labeling for CDS and CD4. CD30 labeling was negative. S‐100 protein was positive on a Langerhans' cell reactive subpopulation. Electron microscopy confirmed the histiocytic nature of malignant cells and showed cytoplasmic inclusions such as regularly laminated bodies, dense bodies and pleomorphic inclusions. No Birbeck granules were seen. A gene rearrangement study of T‐cell receptor γ and immunoglobulin heavy chain genes showed a germline configuration. Histiocytic sarcoma is an extremely rare true histiocytic malignancy, the existence of which has been recently debated since it has often been mistaken in the past for large cell lymphomas. Such a deceptive onset as benign cutaneous histiocytosis has not been described in the literature to our knowledge.
Oral pseudolymphoma: a report of two cases
Authors: Río Emilio del , Yus Evaristo Sánchez , Requena Luis , Puente Luis García , Veiga Hugo Vázquez
Published: April 2006

Although 2% to 10% of lymphomas present first in the oral cavity and lymphomas are the third most common oral malignancy, pseudolymphoma is a very infrequent problem within oral pathology. Two cases of oral pseudolymphoma are presented. Both were old persons with an infiltrative lesion on the oral mucosa that histologically showed a dense polymorphous infiltrate with some nuclear atypia that raised the problem of lymphoma versus pseudolymphoma. Both lesions disappeared with no relapse after 2‐years' follow‐up. Histologically, case 1 was mainly a lymphohistiocytic infiltrate whose histiocytic component showed nuclear features that mimicked Hodgkin's cells. In case 2, the infiltrate was mainly composed of histiocytes and eosinophils. The suspicion of malignancy here was a consequence of a high mitotic rate of histiocytes and of the large hyperchromatic nuclei of the intraepithelial lymphocytes. Similarities and differences with other pseudomalignant (lymphomatoid papulosis and atypical histiocytic granuloma) and inflammatory (traumatic ulcerative granuloma with stromal eosinophilia) disorders, as well as with some histiocytoses, are discussed. In the absence of a wider experience on this subject, an objective description of new cases seems appropriate.
Superinfected cutaneous angiosarcoma: a highly malignant neoplasm simulating an inflammatory process
Authors: Diaz‐Cascajo Carlos , de la Vega Maria , Rey‐Lopez Agustin
Published: April 2006

This report describes a patient with a poorly differentiated cutaneous angiosarcoma (CA) of the face superinfected with pseudomonas aeruginosa. Neoplastic cells were positive for CD‐34, CD‐31 and vimentin, whereas they failed to express other vascular markers such as Factor VIII and Ulex europeaus lectin. The tumor spread rapidly through the skin and the superficial soft tissue before metastasizing. The patient died of disease 6 months after histopathological diagnosis. An autopsy revealed widespread metastases in the lung and the liver. The aim of this report is to call attention to some circumstances in which CA may masquerade as an inflammatory process, delaying the right diagnosis with serious consequences for the patient.
Milia en plaque associated with pseudoxanthoma elasticum
Authors: Cho Sang Hyun , Cho Baik Kee , Kim Chung Won
Published: April 2006

We report a woman with numerous milia occurring in a plaque‐type distribution in the postauricular area, who has suffered from cutaneous pseudoxanthoma elasticum on both sides of the neck. Milia may arise primarily or may follow a number of dermatoses. We believe this is a unique case because milia en plaque coexisting with pseudoxanthoma elasticum does not appear to have been reported previously.
Quantification of vascularity in nodular melanoma and Spitz's nevus
Authors: Binder Michael , Steiner Andreas , Mossbacher Ulrike , Hunegnaw Mesfin , Wolff Klaus , Pehamberger Hubert
Published: April 2006

Spitz's nevi are acquired benign melanocytic skin tumors. Usually they are differentiated from nodular melanoma by clinical and histopathological criteria. Since Spitz's nevi are one of the most common simulators of nodular melanomas their bizarre histopathology may cause diagnostic confusion and make it difficult to differentiate these two melanocytic tumors. One of the histologic features shared by Spitz's nevus and nodular melanoma is prominent vascularity. The ability of malignant melanoma to induce angiogenesis is well established whereas benign melanocytic tumors do not have a prominent overall vascularity.

The purpose of this study was to find out whether the degree of vascularity of nodular melanomas differs significantly from that of benign Spitz's nevi.

In this study the number of microvessels and the vessel area were determined in 23 Spitz's nevi and 16 nodular melanomas. The number of microvessels and the vessel area were determined on Ulex Europacus agglutinin I‐stained sections by computer‐assisted image analysis. Two methods of measurement were used, namely systematic and selective sampling. Measurement of the whole tumor specimen (systematic sampling) revealed a vessel count of 10.83/field (SD±5.97) for Spitz's nevi whereas nodular melanomas exhibited a significantly lower (p=0.04) vessel count of 6.44/field (SD±3.85). This difference was even more pronounced when the vessel area (Spitz's nevi: 17.85×10–4mm2, SD±10.32; nodular melanomas: 7.88×10‐mm2, SD×5.23) was investigated (p < 0.001). The difference in vessel area and vessel count was insignificant for areas exhibiting the greatest vascularity (selective sampling). Measurement of vessel count and vessel area lead us to conclude that Spitz's nevi have a significantly higher vascularity than do nodular melanomas. Our results thus indicate that angiogenesis in these pigmented lesions is not correlated with malignancy.
CD44 variant expression in cutaneous T‐cell lymphoma
Authors: Orteu C. H. , Li W. , Allen M. H. , Smith N. P. , Barker J. N. W. N. , Whittaker S. J.
Published: April 2006

Expression of the lymphocyte homing receptor CD44 and its splice variants have been linked to tumour dissemination and poor prognosis in non‐Hodgkin's lymphoma. Specifically, the in vitro expression of variant exon V6 confers metastatic potential in rat pancreatic carcinoma cell lines. In this study, we investigated the expression of CD44 splice variants in cutaneous T‐cell lymphomas, including patients with mycosis fungoides (MF), Sezary syndrome (SS), large‐cell anaplastic lymphoma (LCAL) and HTLV1‐associated cutaneous lymphoma. In addition, 4 involved lymph nodes from 2 patients with MF and 1 patient with SS were examined. Inflammatory dermatoses, lichen planus and psoriasis, and normal skin were also studied. Immunohistochemistry was performed using a panel of monoclonal antibodies, including those with specificity for CD44H (standard isoform) and variant exons V3, V6 and V8‐9. Normal epidermal keratinocytes were consistently CD44H and CD44 V3, V6 and V8‐9 positive. In all the different clinicopathological subtypes and stages of cutaneous T‐cell lymphomas, including involved lymph nodes, tumour cells consistently expressed CD44H, but were CD44 V3 and V6 negative. CD44 V8‐9 was expressed on a majority of tumour cells in 2/5 LCAL and on occasional tumour cells in 2/5 LCAL. Occasional V8‐9 positive tumour cells were also identified in 6/13 MF, 1/4 SS and 3/4 HTLV1. In 2/3 lymph node samples from 2 patients with tumour‐stage MF, CD44 V8‐9 expression was found on a small percentage of atypical mono‐nuclear cells. Scattered V8‐9 positive dermal mononuclear cells were present in sections of lichen planus and psoriasis. We have found no evidence to suggest that the metastasis‐associated CD44 variant exon (V6) is expressed in cutaneous T‐cell lymphoma, or that CD44H expression is associated with an adverse prognostic group. It is not clear whether the strong expression of CD44 V8‐9 in 2 patients with CD30 positive LCAL reflects activation status or metastatic potential.
Cytoplasmic microtubules in two different mouse melanoma cell lines: a qualitative and quantitative analysis using confocal laser scanning microscopy and computer‐assisted image analysis
Authors: Fink‐Puches Regina , Hofmann‐Wellenhof Rainer , Smolle Josef , Helige Christine , Kerl Helmut
Published: April 2006

The microtubular system as one part of the cellular cytoskeleton is not only necessary for mitotic activity of malignant cells but also for invading neighboring tissues and for the formation of distant metastases. In the present study, the amount and distribution of tubulin in two murine melanoma cell lines (K1735‐M2: high metastatic clone; K1735‐cl16: low metastatic clone) were determined quantitatively using an indirect immunofluorescence technique, confocal laser scanning microscopy (CLSM)and computer‐assisted image analysis. Additionally, qualitative and quantitative changes after application of the microtubule‐inhibitor nocodazole were investigated. Quantitative analysis showed a significant difference between the high and low metastatic cell line for the parameter TEXTURE, indicating a finer structured network within the high metastatic cells. After treatment with nocodazole the parameters TEXTURE and DENSITY were reduced, suggesting a decrease of assembled tubulin and a less delicate structure of the remaining microtubules. Our study shows that CLSM combined with computer‐assisted image analysis provides a new method to examine quantitative variations of the cytoskeleton possibly related to cell function.
Differences in tumor microvessel density between squamous cell carcinomas and basal cell carcinomas may relate to their different biologic behavior
Authors: Weninger W. , Rendl M. , Pammer J. , Grin W. , Petzelbauer P. , Tschachler E.
Published: April 2006

Tumor microvessel density (TMVD) has been recognized as an important indicator for the metastatic risk in certain tumors. The purpose of this study was to analyse whether there is an association of TMVD in epithelial neoplasms of the skin with their clinical behavior. Paraffin sections of keratoacanthomas (KA, n=10), squamous cell carcinomas (SCC, n=9), nodular (nod‐BCC, n=13), and sclerosing (scl‐BCC, n=12) basal cell carcinomas were immunohistochemically stained for factor‐VIII‐related antigen and TMVD was determined. In all SCC, KA and nod‐BCC, TMVD significantly exceeded perilesional skin microvessel density (PSMVD) (SCC:TMVD/PSMVD = 20.54:11.25, p < 0.0001; KA:TMVD/PSMVD = 20.90:12.17, p < 0.0001; nod‐BCC:TMVD/PSMVD = 16.77:13.34, p=0.03). In contrast, no significant difference between TMVD and PSMVD was found in scl‐BCC (15.44:12.86, p=0.22). TMVD was significantly higher in SCC and KA compared to nod‐BCC (p=0.036 and 0.006, respectively). Our data demonstrate that SCC and KA are highly vascularized tumors. The fact that TMVD does not differ significantly between SCC and KA (p=0.80) suggests that MVD is not an indicator for the metastatic risk or aggressive growth behavior of epithelial skin tumors. The finding that MVD in both nod‐ and scl‐BCC is significantly lower than in SCC and KA, might at least in part explain the slow growth of BCC.
Giant intravenous glomus tumor
Authors: Acebo Elvira , Fernando Val‐Bernal J. , Arce Félix
Published: April 2006

We report a painful intravenous glomus tumor located in the right forearm of a 79‐year‐old woman. The tumor originated from the wall of a vein, protruded into its lumen and was completely excised. The largest dimension of the tumor occluding the vein was 14 cm. Tumor cells were characterized immunohistochemically by the presence of vimentin, α‐smooth‐muscle actin, and collagen IV. Intravascular spread of the glomus tumor is rare and has been described in the stomach and subcutaneous tissue. An entirely intravenous glomus tumor has been reported only three times. However, a huge intravenous growth as in our case appears never to have been reported. A review of the intra‐vascular cases showed that the average age of presentation is 61.5 years (range 40–79 years) and the most frequent location is the forearm. Despite this intravascular growth, there is no evidence of aggressive clinical behavior, recurrence or metastasis. The pathologist must be aware of this variant of glomus tumor to avoid misdiagnosis and unnecessary additional treatments.
Immunohistochemical analysis of platelet‐derived growth factor and its receptors in fibrohistiocytic tumors
Authors: Taniuchi Katushige , Yamada Yuuko , Nonomura Akitaka , Takehara Kazuhiko
Published: April 2006

Platelet‐derived growth factor (PDGF) is known to stimulate the proliferation of fibroblasts, although the role of PDGF and its receptors in the development of fibrohistiocytic tumors has not been clarified. In this study, we investigated this role by immunohistochemically staining PDGF and PDGF β‐receptors in paraffin‐embedded dermatofibroma (DF), dermatofibrosarcoma protuberans (DFSP) and malignant fibrous histiocytoma (MFH) tissue. We also immunohistochemically investigated the relationship between PDGF β‐receptors and CD34, which is a known immunohistochemical marker for DFSP. Immunohistochemical studies using anti‐PDGF‐AA or BB antibodies showed that PDGF‐AA and BB was found in 20 to 40% of the tumor cells in DF, DFSP, and MFH. No definite relationship for each tumor type was found. The expression of PDGF β‐receptors in DFSP and that of MFH tissue was significantly greater in comparison to DF and scar tissue. The expression of CD34 and PDGF β‐receptors in DFSP was observed in identical areas. These findings suggest that autocrine or paracrine growth stimulation, through PDGF β‐receptors, is related to the tumorous proliferation of fibrohistiocytic tumors, and the expression of PDGF β‐receptors might play a role in the proliferation of CD34 positive tumor cells.