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We have been investigating differential gene expression associated with apoptosis in AK-5 cells (a spontaneously regressing rat histiocytoma) and have observed catalytic subunits beta 7 and alpha 5 of the 26S proteasome and ubiquitin to be upregulated during apoptosis induced by a variety of agents. The observed elevation in gene expression was parallel to a comparable increase in the cytosolic protein expression of the proteasome and ubiquitin and a markedly amplified increase in the proteasome activity. Inhibition of the increase in gene expression resulted in the inhibition of the rise in the proteasome activity subsequently leading to an inhibition of apoptosis. Similarly, pretreatment with proteasome inhibitors, MG132 and lactacystin, resulted in a significant inhibition of apoptosis pointing to the requirement of a highly active protein degradation machinery during apoptosis. The apoptosis inhibitory effect of the proteasome inhibitors involved an inhibition of the activation of various initiator and effector caspases but was independent of any changes in the mitochondrial membrane depolarization and cytochrome c release associated with apoptosis. Inhibition of proteasome activity or its upstream PI3 kinase activity inhibited NFkappaB translocation thereby suppressing apoptosis, which highlights the requirement of NFkappaB activation for completion of apoptosis in AK-5 cells. Hence, the apoptosis associated induction of the Ub-proteasome pathway components and the proteasome activity suggests that the proteasome, in its capacity as an efficient protein degradation complex, plays an important role in the successful execution of apoptosis.

Background: Multinucleate cell angiohistiocytoma is an infrequent and most likely non-neoplastic disorder usually seen in acral regions in elderly women. It presents clinically as asymptomatic red-to-brown tumors, with a tendency to confluence. It must be distinguished from other diverse cutaneous lesions, notably dermatofibroma, Kaposi sarcoma, and angiofibroma., Methods: We report the clinical, histopathological, and immunohistochemical findings of five patients, all women aged between 51 and 78 years. All except the first presented lesions on both of the lower limbs. None of the patients developed spontaneous resolution of the lesions and one was successfully treated by cryosurgery., Comments: Multinucleate cells are characteristic, but neither exclusive nor pathognomonic, of multinucleate cell angiohistiocytoma, since they can also appear in other inflammatory, neoplastic, or reactive processes. The presence of these cells and vascular proliferation in dermis media are the principal histopathological findings in this infrequent entity. In immunohistochemical studies, the multinucleate cells are often positive for vimentin and factor XIIIa.

We present the case of a 64-year-old male who developed multiple asymptomatic papules over a four-month period, distributed symmetrically on the trunk and proximal regions of the limbs, while the scalp, palms, soles and mucous membranes were spared. The lesions were discrete papules, brownish-erythematous, rounded, ranging from slightly raised to hemispherical, from 1 to 3 mm in diameter and firm to the touch. Clinical, histopathological, immunohistochemical and ultrastructural studies were consistent with generalized eruptive histiocytoma. Laboratory tests and radiological studies did not show any abnormal findings. After being subjected to photochemotherapy, the lesions regressed, but later on new outbreaks of papules appeared. Generalized eruptive histiocytoma belongs to a spectrum of diseases that may overlap; some may even develop into others. As the disease may progress into a more serious ailment, regular checkups with clinical, histological and immunohistochemical examinations should definitely be considered.

A 50-year-old woman was admitted due to a long-standing history of cutaneous lesions, which were gradually increasing in number and size, located on the trunk and extremities. Histological studies confirmed the initial clinical diagnosis of histiocytomas. Moreover, the patient had numerous smooth erythematous papules on her chin and around her nose, which were diagnosed histologically as angiofibromas. The patient had congenital phocomelia. Analytical and imaging studies revealed the presence of bilateral phocomelia due to absent radii and thrombocytopenia (TAR syndrome). Multiple histiocytomas in a normolipaemic patient bring up several differential diagnoses. Slow progressive evolution without spontaneous resolution and a scattered distribution on the trunk and extremities suggest the diagnosis of progressive nodular histiocytoma. To our knowledge progressive nodular histiocytoma has not been reported previously associated either with TAR syndrome or with angiofibromas. These entities are uncommon, thus their association may not be due to chance.

Sarcomas are relatively uncommon tumors, accounting for 1% of all malignancies. Sarcomas are commonly classified according to their site of origin: soft tissues or bone. The purpose of the clinic study was to focus the symptoms and the clinic signs. The radio-imaging study is essential in the evaluation of the maxilla tumors. The histopathologic study was done to determine the histological type, the differentiation level, the invasion level as well as the presence or absence of the metastases in drainage ganglia. The correlation of the findings of this study leads to a clear and correct clinic diagnosis, an adequate local or general therapy and a prognostic. The diagnostic role of imaging is essential and often permits the orientation to benignity or, on the contrary, requires biopsy if the image is an aggressive one or of uncertain nature. Advances in diagnostic imaging have contributed substantially to the management of tumors. The strong collaboration among the physician, imaging personnel and anatomo-pathologist serves the patient's benefit.

Erythema elevatum diutinum (EED) is a chronic cutaneous vasculitis occurring in association with a variety of conditions including autoimmunity, infectious disease, and hematological abnormalities. The role of associated medical problems is controversial, and the exact pathogenesis of EED is unknown. A series of six cases is reported. The typical clinical presentation was that of erythematous papules and plaques involving the extensor surfaces of the extremities. Histologically, a spectrum from leukocytoclastic vasculitis to vessel occlusion and dermal fibrosis was seen. The lesions of EED have many mimics clinically and histologically. Establishing the diagnosis of EED is important so appropriate screening for associated conditions can ensue. The vascular endothelium of EED stains positive for CD31, CD34, VEGF, and factor VIIIa and negative for factor XIIIa, TGFB, and LANA, a reaction pattern that does not distinguish it from similar appearing lesions. Thus, the chronic and recurrent nature of EED is the primary means of distinguishing it from entities that are clinically and histologically similar.

We describe the case of a 50-year-old woman with a lung tumor composed of crystal-storing histiocytes. These cells and associated plasma cells failed to show clonal light chain restriction, and the patient had no associated hematologic disorder. The differential diagnosis included crystal-storing histiocytosis, characterized by accumulation of crystallized immunoglobulins, a rare manifestation of monoclonal gammopathies/plasma cell dyscrasias. Crystal-laden histiocytes have previously been described in many organs. Four reports have described crystal-storing histiocytosis in the lung, always associated with a lymphoproliferative disorder. The present patient, 1 other case from our archive, and 1 case reported in the literature, all without an association with lymphoproliferative disorder, make a full description and definition of this lesion appropriate. The morphology, immunohistochemical profile, and electron microscopic features are described herein, and the term pulmonary crystal-storing histiocytoma is proposed. A practical algorithm is presented for the assessment of solitary lung masses composed of large histiocytic cells.