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A 72-year-old white man presented with a large cutaneous tumor on his back. The patient said the lesion, mostly asymptomatic, had increased in size for about 7 years. Physical examination revealed a vegetating mass (Figure 1), partially ulcerated, measuring 30 x 20 cm, which easily dripped serum and blood, with small necrotic areas and a sclerotic border. Perilesional skin appeared edematous, probably owing to inflammation and impaired lymphatic flow. Clinically, there was no evidence of lymph node involvement. His family history was noncontributory. Hematologic examination revealed hypochromic microcytic anemia. Laboratory test results showed hyperuricemia and hypercholesterolemia. The patient's history revealed mild hypertension, ischemic cardiopathy treated with percutaneous transluminal coronary angioplasty and anticoagulant drugs, and moderate chronic renal insufficiency. Histologic examination of a biopsy specimen taken from the margin of the lesion displayed a superficial area of ulceration and invasion of the deeper dermis and subcutaneous tissue (Figure 2A and Figure 2B). The tumor mostly showed an adenoid pattern: gland-like structures and cystic spaces sometimes containing amorphous or granular material, surrounded by strands of basaloid cells devoid of any peripheral palisading (Figure 2C). In some areas, the adenoid pattern coexisted with infiltrated areas characterized by thin and elongated strands or cords of basaloid cells with irregular and jagged peripheral contours within a fibrous or edematous stroma (Figure 2D). Basaloid cells often revealed nuclear atypia, marked pleomorphism and hyperchromatism (Figure 2C and Figure 2D). Therefore, a diagnosis of basal cell carcinoma, adenoid subtype, was made. Magnetic resonance imaging showed a 10-cm wide thickening of the subcutaneous layer on the lumbar region, with a partial neoplastic infiltration of the muscle fascia. No evidence of metastases was found with a total body computed tomography scan. Because the patient was taking anticoagulant drugs and had unstable renal and cardiac function, surgical treatment was at least temporarily excluded, and the patient was referred for radiation therapy.

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.

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).

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.

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.

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.

Brucellosis is endemic in the Mediterranean area. In spite of the false negative results, the standard agglutination test remains the routine test for the diagnosis of brucellosis in southern Italy. We present a case of a patient with undulant fever and erythema nodosum-like skin lesions, with negative serum agglutination test, but isolated positivity of the ELISA test for anti-Brucella IgM. A diagnosis of brucellosis for this patient was supported by the anamnestic and clinical data, and by the response to therapy. This case and a review of the literature urge us to consider the ELISA test indispensable for the serological diagnosis of brucellosis.

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.

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.

Canalicular adenoma is an uncommon benign neoplasm that occurs almost exclusively in the upper lip and, very rarely, in other sites. We describe a case arising in the left parotid gland as a firm, painful mass, in order to underline morphological and immunohistochemical findings, particularly in relation to differential diagnosis with low-grade carcinomas of the salivary glands.

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.

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 (beta2-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.

In this report we have investigated the effects of BAX in enhancing apoptosis in two primary non-small cell lung cancer cell lines. A count of the apoptotic cells by TUNEL staining revealed that almost 70% of BAX over-expressing cells died, while very few apoptotic cells were detectable in the wildtype cells or in the cells transfected with an empty vector. These findings suggest that de-regulated expression of BAX may provide a novel mechanism for initiating cell death in non-small cell lung cancer cells. Further studies are needed to better define the involvement of this protein in the complex mechanism of lung carcinogenesis and to definitely demonstrate the therapeutic utility of targeting this pathway.

The expression of cyclin T1 in an autoptic case of AIDS-related cachexia was investigated by immunohistochemistry. When contrasted with normal human tissues, a very similar pattern of expression was found. However, a peculiar distribution of cyclin T1 was noticed in the brown fat and in lymph nodes affected by AIDS-associated lymphadenopathy.

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.