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Kaposi's Sarcoma (KS) of the tongue is extremely rare in immunocompetent patients. We report a case of KS of the tongue associated with a median rhomboid glossitis. The main clinical, pathological and immunohistochemical features allowed the differential diagnosis.

In order to identify genes relevant for melanoma development, we carried out cDNA array experiments employing an in vitro model of human melanoma progression, consisting of two cell lines: one, LP, derived from a primary melanoma and the other, LM, from its metastatic supraclavicular lymph node. Basic cDNA array data identified 26 genes as down-regulated in the LM cell line. Northern blot analysis confirmed an effective transcriptional down-regulation for five out of 13 genes analyzed. The products of these five genes belong to different functional protein types, such as transcription and translation regulators (Edg-2, eIF-3 p110, and RNPL/RBM3), extracellular communicators (PRSS11) and members of the major histocompatibility complex (β2-microglobulin). Some previously described differences in expression patterns, such as loss of HLA I, were confirmed by our array data. In addition, we identified and validated for the first time the reduced expression level of several genes during melanoma progression. In particular, reduced Edg-2 gene product expression was also confirmed in a group of 50 primary melanomas and unrelated metastases. In conclusion, comparative hybridization by means of cDNA arrays assisted in identifying a series of novel progression-associated changes in gene expression, confirming, at the same time, a number of previously described results. © Blackwell Munksgaard, 2003.

The authors describe a rare case of peritoneal mesothelioma. Cytological, histological and immunohistochemical characterization of the tumor allowed the differential diagnosis from papillary carcinoma and suggested the diagnosis of leiomyoid mesothelioma.

Two cases of Merkel cell carcinoma (MCC) of the head and neck region are reported in order to stress their diversity in morphological, immunohistochemical and clinical findings. The remarkable variability of MCC has been analyzed, particularly in relation to the differential diagnosis and prognostic implications.

Vulvar dermatofibrosarcoma is a rare fibrous tumor of intermediate grade malignancy, with a tendency for local recurrence, and rarely metastasizes. Management should be multidisciplinary. This is a report of an apparently benign vulvar mass with delayed diagnosis of vulvar dermatofibrosarcoma.A 42-year-old woman was referred to our hospital because of a vulvar tumor lasting 16 years, although several gynecological procedures and a total laparoscopic hysterectomy had been performed two years before. During this long period the lesion did not change morphological features and remained asymptomatic. Only a benign vulvar mass was diagnosed. Then, the swelling became evident showing erythematous skin with an aspect of "peau d'orange", leading the patient to consult a specialist. A firm vulvar swelling was observed in the anterior third of right labia majora continuing with about 3 cm of cord on top, quite movable above the underlying tissue but not on the overlying tissue. A wide excision was performed. The pathological examination showed positive margins. One month later an extensive deeper excision was performed. Histology confirmed a diagnosis of dermatofibrosarcoma. Immunohistochemistry was strongly positive for CD34.Vulvar lesions always require complete pathologic examination even in case of features of benign tumor to exclude a dermatofibrosarcoma. The role of the pathologist is essential to ensure negative microscopic margins and to avoid local recurrence.

A 24-year-old woman was seen in consultation for a painless tumor of 6 cm in diameter of the vulva. The excised oval tumor was situated in the lower part of the dermis and encapsulated (Fig. 1A). It was completely composed of multiple adjacent cell complexes, each containing 5–20 laminar cells and resembling Wagner–Meissner touch corpuscles (Fig 1B and 1C). The nuclei of the laminar cells were located at the periphery of the corpuscles or were arranged transversely to the long axis of these structures along the lamellae. The nuclei were oval or showed one or several nuclear invaginations. Mitoses were not observed. These corpuscles showed a positive immunohistochemical reaction for S-100 (Fig. 1D), vimentin, and neuron-specific endase (NSE) (not shown), but were negative for CD-68, desmin, and α-actin. The gross and microscopic morphology and the immunohistochemical findings were compatible with a diagnosis of Wagner–Meissner neurilemmoma of the vulva. The patient remained disease free for 2 years after surgery. Figure 1. (A) Gross appearance of the excised oval tumor of the vulva, situated in the lower part of the dermis and encapsulated. (B) Histologic examination of the excised lesion revealed a monomorphous morphology with typical touch corpuscles with lamellar structures (hematoxylin and eosin; original magnification, × 50). (C) Higher magnification of (B). The nuclei are predominantly located at the periphery of the corpuscles (hematoxylin and eosin; original magnification, × 250). (D) The tactile corpuscles show a positive reaction for protein S-100 (3-amino-9-ethylcarbazide, × 250) Download figure to PowerPoint

A wide range of diseases may present with radiographic features of osteolysis. Periapical inflammation, cysts and benign tumours, bone malignancies, all of these conditions may show bone resorption on radiograph. Features of the surrounding bone, margins of the lesion, and biological behaviour including tendency to infiltration and root resorption, may represent important criteria for distinguishing benign tumours from their malign counterpart, although the radiographic aspect of the lesion is not always predictive. Therefore a critical differential diagnosis has to be reached to choose the best management. Here, we report a case of giant cell tumour (GCT) whose radiological features by computed tomography (CT) suggested the presence of bone malignancy, whereas the evaluation of a routine OPT scan comforted us about the benign nature of the lesion. A brief review of the literature on such a benign but locally aggressive neoplasm is also provided.

Nearly 25% of non-Hodgkin lymphomas (NHLs) arise in extranodal locations. The involvement of soft tissue by NHL is uncommon. Primary extranodal NHL of the skeletal muscle is even rarer. The authors report a 49-year-old man with a 3-month history of progressive asymmetry of the face caused by swelling in the right cheek with paresthesia and burning. He underwent an excisional biopsy of the lesion. Histologic examination, immunohistochemistry and cytogenetic analysis were performed. The final diagnosis was primary large B-cell NHL of the masseter muscle, stage IEA. Rituximab-cyclophosphamide, epirubicin, vincristine and prednisone regimen was started. Restaging procedures after immunopolychemotherapy showed no evidence of disease. No relapse has occurred during a follow-up of 72 months. Although primary muscle lymphoma represents a rare entity, it can involve every muscle. Thus, when patients present with cheek swelling, physicians should always consider the possibility of lymphoma. The authors also reviewed the published literature concerning primary muscle lymphoma. © 2011 Lippincott Williams &Wilkins.

A scleroderma-like cutaneous syndrome, occurring after implantation of a prosthetic knee joint in an elderly woman, is reported. This case did not seem to typically fit into any of the known scleroderma-like disorders of the skin described to date. The patient was shown to be sensitized to metals contained in the prosthesis and to mount a Th2-type immune response concomitantly with development of skin fibrosis. In particular, eosinophilia, markedly elevated serum IgE levels, in vitro spontaneous production of interleukin (IL)-4 by T lymphocytes, and elevated serum levels of Th2 cytokines (namely, IL-4, IL-5, and IL-13) were observed during the acute phase of illness. Since eosinophils and such Th2 cytokines as IL-13 also have recognized fibrogenic properties, it is speculated that the pathogenesis of skin fibrosis in this case could have been the direct and/or indirect consequence of the coexisting Th2-type immune response.

Hypertrophic scar (HS) and keloid (KL) are two forms of an abnormal cutaneous scarring process, mainly characterized by excessive extracellular matrix deposition and fibroblast proliferation. Despite the increased understanding of the molecular and cellular events leading to HS and KL, the pathogenesis of these lesions remains poorly understood. A pivotal role in the formation of abnormal scars has been ascribed to transforming growth factor-beta, whose activity appears to be mediated through a link with pathways acting via cyclooxygenases (COX-1 and COX-2). To date, there is no report on the in vivo expression of COX-1 and COX-2 in human HS and KL tissues. Therefore, using immunohistochemistry and Western blot analysis, we investigated 36 cases of KL, 32 cases of HS, and 25 cases of normal skin in order to define the localization and distribution of COX-1 and COX-2 in the tissues of these scar lesions and the overlying epidermis. The results mainly show the following: (a) a significant overexpression of COX-1 in HS tissues and the overlying epidermis as compared with normal skin and KL tissues and (b) a significant overexpression of COX-2 in KL tissue and the overlying epidermis in contrast to normal skin and HS tissues. Our data support the hypothesis that both COXs are involved in the pathogenesis of scar lesions in different ways and, particularly, COX-1 in the formation of HS and COX-2 in the formation of KL. In addition, the overexpression of COX-1 and COX-2 in the epidermis overlying HS and KL tissues, respectively, underlines the importance of epithelial-mesenchymal interactions in the pathogenesis of scar lesions.

The pathogenesis of pemphigus vulgaris (PV) is still poorly understood. Autoantibodies present in PV patients can promote detrimental effects by triggering altered transduction of signals, which results in a final acantholysis. To investigate mechanisms involved in PV, cultured keratinocytes were treated with PV serum. PV sera were able to promote the cell cycle progression, inducing the accumulation of cyclin-dependent kinase 2 (Cdk2). Microarray analysis on keratinocytes detected that PV serum induced important changes in genes coding for one and the same proteins with known biological functions involved in PV disease (560 differentially expressed genes were identified). Then, we used two different approaches to investigate the role of Cdk2. First, small interfering RNA depletion of Cdk2 prevented cell-cell detachment induced by PV sera. Second, pharmacological inhibition of Cdk2 activity through roscovitine prevented blister formation and acantholysis in the mouse model of the disease. In vivo PV serum was found to alter multiple different pathways by microarray analysis (1463 differentially expressed genes were identified). Major changes in gene expression induced by roscovitine were studied through comparison of effects of PV serum alone and in association with roscovitine. The most significantly enriched pathways were cell communication, gap junction, focal adhesion, adherens junction, and tight junction. Our data indicate that major Cdk2-dependent multiple gene regulatory events are present in PV. This alteration may influence the evolution of PV and its therapy. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc.

According to a two-step procedure, the diagnosis of basal cell carcinoma (BCC) is based on the absence of melanocytic criteria (i.e., pigment network, dots/globules, cobblestone pattern, homogeneous blue pigmentation, streaks, and/or parallel pattern) and the presence of the following specific features: large gray-blue ovoid nests, spoke wheel areas, multiple gray-blue globules, leaflike areas, ulceration, and arborizing ‘‘treelike’’ telangiectasias, which allow correct diagnosis with high confidence. We report a case of pigmented BCC showing, besides the ‘‘classic’’ dermoscopic features of BCC, a pigment network and discuss the underlying histopathologic correlate of this unusual finding.

Objective To investigate changes in dermoscopic patterns of acquired acral melanocytic nevi (AAMN) over time. Design Retrospective analysis of digital dermoscopic follow-up of 230 AAMN located on acral volar skin. Setting Outpatient clinics at university dermatology departments. Patients A total of 230 AAMN located on the soles (n = 149), fingers (n = 62), and palms (n = 19), of 230 white subjects 14 years or younger (n = 81), 15 to 30 years (n = 72), and older than 30 years (n = 77). Main Outcome Measure Comparison of baseline and follow-up dermoscopic patterns. Results Individual AAMN had a digital follow-up of 6 months (n = 59), 12 months (n = 74), 18 months (n = 44), and 24 months (n = 53). Baseline dermoscopic images showed the following patterns: parallel furrow (48.8%), latticelike (16.1%), fibrillar (10.9%), nontypical (10.9%), homogeneous (4.8%), globular (3.5%), transition (3.5%), and reticular (2.6%). Dermoscopic changes over time were observed in 42 of the 230 AAMN (18.3%), with the greatest frequency of changes occurring in patients 14 years or younger (23 of 81 lesions; 28.4%) ( P = .005). The parallel furrow pattern (25.9%) showed more variations over time than other dermoscopic patterns (11.0%) ( P = .004). The frequency of change increased linearly over time ( P = .001). Four of 7 clinically regressing nevi showed a homogeneous pattern at the last examination. Conclusions Dermoscopic changes of AAMN are most common in subjects younger than 14 years. The parallel furrow pattern appears to be the dermoscopic pattern most subject to change, while the homogeneous pattern may be seen also in AAMN showing clinical and dermoscopic involution.

Cyclooxygenases (COXs) are enzymes catalysing prostaglandin synthesis and are implicated in the carcinogenesis of some cancer types. In addition, an important role of these enzymes in herpesvirus infections was demonstrated and it has recently been proposed that COX-2 may participate in herpesvirus-induced neoplasia such as Kaposi's sarcoma (KS). To date no immunohistochemical study has been performed to determine the identification of COX-1 and COX-2 in KS. We have investigated 35 cases of classic KS and 27 cases of epidemic KS form in order to study the distribution and localisation of COXs. We have examined by immunohistochemistry the expression of COX-1 and COX-2 in classic and epidemic forms of KS also in relationship to the characteristic morphological phases (patch, plaque and nodular stage) of KS and cell localisation by double immunostaining. Moreover, we have obtained COX-1 and COX-2 expression by Western blot analysis. Our results establish that (a) COX-1 and COX-2 are overexpressed significantly in classic and epidemic KS compared with control skin tissues (P < 0.01 and P > 0.03, respectively, for COX-1; P < 0.01 and P > 0.03, respectively, for COX-2); (b) the extent and intensity staining for both COXs were higher in classic than in epidemic form of KS. Our data support the hypothesis that both COXs may be involved in the pathogenesis of KS. © 2007 Elsevier Ltd. All rights reserved.

Pemphigus vulgaris (PV) acantholysis represents a complex phenomenon wherein a number of factors cooperates. PV serum is known to modulate important cellular events, including kinase activity, transcriptional regulation, and proteinase expression. Indeed, transduction of signals to the cell triggered by PV serum may induce proteinase up-regulation potentially responsible for disruption of epidermal adhesion and, ultimately, blister formation. Here, we sought to investigate this hypothesis by using both in vivo and in vitro models of PV. Microarray analysis on mouse skin tissues suggested that the equilibrium between extracellular proteinases and their inhibitors moved towards enhanced proteolytic activity in PV neonatal mouse model, at least on the transcriptional level. Conversely, genes codifying cell adhesion proteins were dramatically down-regulated. The effects of PV serum on the protein level were then studied in vitro both in keratinocyte monolayers and skin organ cultures focusing on matrix metalloproteinase (MMP) 9 expression and activity. By means of Western blotting, zymography, and living cell immunofluorescence studies, we showed that MMP-9 was early overexpressed in keratinocytes exposed to PV serum, and subsequently secreted in the culture medium. However, we failed to demonstrate extracellular activation of MMP-9, since it was found in its 92 kDa inactive form in serum-free culture supernatants. Taken together, our data demonstrated that proteinase expression, particularly of MMP-9, is modulated by PV serum and associated with PV acantholysis.

Peripheral arterial disease (PAD) is a major health problem especially when associated to diabetes. Administration of autologous bone marrow cells (BMC) is emerging as a novel intervention to induce therapeutic angiogenesis in experimental ischemic limb models and in patients with PAD. Since tissue ischemia and diabetes are associated with an overwhelming generation of oxygen radicals and detrimental effects due to formation of glycosylation end-products, metabolic intervention with antioxidants and L-arginine can confer beneficial effects beyond those achieved by BMC alone. The effects of cotreatment with intravenous BMCs and metabolic vascular protection (1.0% vitamin E, 0.05% vitamin C, and 6% L-arginine) were examined in the ischemic hindlimb of diabetic and non diabetic mice. BMC therapy increased blood flow and capillary densities and Ki67 proliferative marker, and decreased interstitial fibrosis. This effect was amplified by metabolic cotreatment, an intervention inducing vascular protection, at least in part, through the nitric oxide pathway, reduction of systemic oxidative stress, and macrophage activation.

BACKGROUND: The starburst pattern is the dermoscopic hallmark of pigmented Spitz nevus, although it has been rarely observed in melanoma as well. OBJECTIVE: To describe a case of melanoacanthoma simulating pigmented Spitz nevus. MATERIAL AND METHODS: Clinical, dermoscopic, and histopathologic examinations were performed for the occurrence of a 4-mm pigmented skin lesion on the hip of a 38-year-old Caucasian woman. RESULTS: Dermoscopy examination of the lesion disclosed a stereotypical starburst pattern characterized by pigmented streaks symmetrically distributed at the periphery. A preoperative diagnosis of pigmented Spitz nevus was made, and the lesion was excised. However, subsequent histopathologic examination revealed a melanoacanthoma. CONCLUSION: The starburst pattern, although diagnostic for pigmented Spitz nevus, can be rarely observed in other benign or malignant pigmented skin lesions. Accordingly, all lesions in adults exhibiting a starburst pattern or other spitzoid features should be excised for histopathologic evaluation.

An 11-month-old male infant was referred to our clinic because of a painful ulcer of approximately 5 months' duration on the ventral surface of the tongue (Fig. 1). On physical examination, the lesion was circular (3 cm x 2 cm) with erythematous, raised, and indurated borders. No pathologic findings emerged from the laboratory data, neurologic examination, or clinical history. The family history was also negative for developmental disorders and congenital syndromes. No biopsy was performed in view of the age of the infant, the particular site of the lesion, and the clinical evidence of diagnosis. The treatment included odontologic cream (methylvinylether/maleic acid) as a protective shield, a collutorium (chlorhexidine 0.2%), and the use of a teething ring. Complete healing of the lesion (Fig. 2) occurred within 3 weeks.

Purpose: Employing an in vitro model system of human melanoma progression, we previously reported ferritin light chain (L-ferritin) gene overexpression in the metastatic phenotype. Here, we attempted to characterize the role of ferritin in the biology of human melanoma and in the progression of this disease. Experimental Design: Starting from the LM human metastatic melanoma cell line, we engineered cell clones in which L-ferritin gene expression was down-regulated by the stable expression of a specific antisense construct. These cells were then assayed for their growth capabilities, chemoinvasive properties, and sensitivity to oxidative stress. Additionally, ferritin protein content in primary and metastatic human melanomas was determined by immunohistochemistry. Results: Artificial L-ferritin down-regulation in the LM cells strongly inhibited proliferation and chemoinvasion in vitro and cell growth in vivo. In addition, L-ferritin down-regulated cells displayed enhanced sensitivity to oxidative stress and to apoptosis. Concurrently, immunohistochemical analysis of a human melanoma tissue array revealed that ferritin expression level in metastatic lesions was significantly higher (P < 0.0001) than in primary melanomas. Furthermore, ferritin expression was constantly up-regulated in autologous lymph node melanoma metastases when compared with the respective primary tumors in a cohort of 11 patients. Conclusions: These data suggest that high ferritin expression can enhance cell growth and improve resistance to oxidative stress in metastatic melanoma cells by interfering with their cellular antioxidant system. The potential significance of these findings deserves to be validated in a clinical setting.

Primary cardiac lymphoma (PCL), defined as a lymphoma clinically mimicking cardiac disease, with the bulk of the tumor located intrapericardially, is extremely rare in immunocompetent patients. Clinical manifestations vary depending on sites of involvement in the heart and include chest pain, arrhythmias, pericardial effusion, and heart failure. Diagnosis is often difficult and may require invasive procedures; in some cases, diagnosis is not made until autopsy. Histologically, nearly all cases of PCL reported thus far have been of B-cell origin. In this report, we describe a case of PCL of T-cell origin in an adult immunocompetent patient, the second reported in the literature to the best of our knowledge, and provide a brief overview of the features of previously published PCL cases.

Infiltrating lipoma (IL) is a rare benign tumour of mesenchymal origin which infiltrates adjacent muscle and tend to recur after excision. Few case of IL have been reported in the literature. Therefore, we will report a case of infiltrating lipoma of the tongue in a 54-year-old Italian male mainly to stress clinical and diagnostic features.

Dermoscopy is a noninvasive diagnostic technique that improves the diagnostic accuracy of pigmented skin lesions. It permits to differentiate melanoma from seborrheic keratosis by detecting the presence of specific dermoscopic features, eg, atypical pigment network and blue-white veil in melanoma, and comedolike openings and milialike cysts in seborrheic keratosis, to name but a few differential diagnostic criteria. We report the dermoscopic-pathologic correlations of a melanoma in situ simulating a seborrheic keratosis on clinical and dermoscopic examinations.

A 35-year-old man presented with a 7-year history of gradually enlarging plaques on his face and trunk. The first lesions had developed on both sides of the forehead and the left cheekbone (Figure 1). Four years later similar lesions appeared on his neck and back. He presented a histologic report of a biopsy specimen from a facial plaque performed 5 years earlier that was diagnostic for granuloma faciale. He had different treatments such as topical steroids and cryotherapy without improvement. The appearance of new lesions on his trunk and the gradual enlarging of the old lesions convinced the patient to seek further treatment. Physical examination revealed dusky, violaceous plaques and papules, 0.5 to 2 cm, well-circumscribed, slightly elevated, and located on the face and trunk, with mild pruritus (Figure 1 and Figure 2). Laboratory investigations, including complete blood cell count, VDRL test, antinuclear antibody test, biochemical parameters, and chest x-ray, did not reveal any abnormalities. A skin biopsy taken from the upper part of the back showed similar features to the facial lesion, detected 5 years before, revealing a dense, polymorphous infiltrate involving mid and deep dermis and displaying a diffuse and perivascular pattern (Figure 3A). A narrow grenz zone of normal collagen was consistently observed between dermal infiltrate and epidermis as well as around the pilosebaceous follicles (Figure 3A). The infiltrate mainly consisted of eosinophils and lymphocytes, but neutrophils (often displaying leukocytoclasis), macrophages, and plasma cells were also present (Figures 3B, 3C). Some mast cells were also identified by staining with toluidine blue (Figure 3D). Perivascular infiltrates were often seen, sometimes penetrating vessel walls and in association with leukocytoclasis. Hyalinization of vessel walls, extravasation of red blood cells around capillaries, and nuclear dust were also noted. The epidermis did not show any remarkable change except for slight acanthosis. A diagnosis of granuloma faciale with extrafacial lesions was made, and a systemic therapy with hydroxychloroquine (200 mg twice daily for 6 weeks) was recommended.(1,2).