Photodynamic treatment of basal cell carcinoma and squamous cell carcinoma with hypericin.

Hypericin displays antiproliferative and cytotoxic effects on tumor cells. This effect depends on photodynamic activation with visible light and oxygen. Hence, we explored its potential use in treating skin cancer. Eight patients with squamous cell carcinoma (SCC) and eleven patients with basal cell carcinoma (BCC) were treated topically with hypericin. After intralesional injection, the hypericin was irradiated with visible light. Patients with SCC were given 40-100 micrograms hypericin intralesionally, 3-5 times per week for 2-4 weeks; patients with BCC 40-200 micrograms hypericin 3-5 times per week for 2-6 weeks. Hypericin displayed selective tumor-targeting: penetration in the surrounding tissues did not induce necrosis or cell loss and even the generation of a new epithelium at the surface of the malignancy was noticed. The effectiveness of the therapy depends on the concentration and total dose of hypericin, the frequency and duration of the therapy; clinical remissions can be expected after 6-8 weeks.

Histopathological aspects of pulmonary carcinoid tumors.

Pulmonary carcinoid tumors are considered low grade malignant tumors, arising from neuroendocrine cells from bronchial mucosa. The small cell proliferation is arranged in small nests or trabeculae, the nuclei are round to oval with finely dispersed chromatin, indistinct nucleoli, small amount of cytoplasm, indistinct borders. Problems of differential diagnosis could appear in distinction with others malignancies like adenocarcinomas, squamous cell carcinomas, lymphomas and others neuroendocrine tumors, especially in the different prognosis and therapeutic approach. We described 15 cases of pulmonary carcinoid tumors diagnosticated by morphologic and immunohistochemical methods.

Morphological and immunohistochemical features of tumor infiltrating lymphocytes (TIL) in carcinomas. Note I.

Some malignant tumours like testicular seminomas and ovarian dysgerminomas or medullar carcinoma of the breast, present an unusually lympho-histiocytic (TIL) rich stroma. Many reports have concluded that the prognosis for these patients is correlated with the intensity of TIL. Recently, some analyses consider that tumour-host interactions have a significant prognostic role in many other neoplasms. The presence of TIL may be a sign of less aggressive behaviour of some epithelial neoplasm like gastro-intestinal, pulmonary, mammary, urinary or cutaneous carcinomas (Wilson et al.). The aim of this study is a morphological and immunohistochemical (IHC) characterisation of the lympho-histiocytic populations of TIL in some gastro-intestinal and mammary carcinomas. The two localisation were chosen for their different contact with the exogene antigens and their possible different type of host's immune response.

Immunocytomorphological study on the pathogenesis of ankylosing spondylarthritis.

The present investigation is based on the cytomorphological, histopathological (HE, VG, PAS-Alcian, Safranin 0, Gömöri), histoenzymological (acid phosphatase, chondroitinsulphatase, peroxidase) and immunological (rheumatoid factor (RF), circulating immune complexes (CIC), anticolagen II antibodies and C reactive protein (CRP) study on ankylosing spondylarthritis (2.5 cases). The synovial fluid (SF) synoviocytogram showed cytosis (6.067/mm3), with polynucleosis (65.19%) and ragocytosis (17.73%) as compared with the hydrarthrosie SF characterized by lymphocytosis (47%). Enzymological findings revealed phosphatasic and myeloperoxidasic activity in the ragocytary polymorphonuclear (PMNs) and mononuclear cells. Histopathologically, the severe forms of AS correlated with villous chronic synovitis, associated to processes of obliterating vascularitis, fibrosclerosis, necrosis and calcification of disintegrated synovial structures. The articular cartilage was severly damaged, while osseous necrobiosis was noted at the osteocartilaginous junction. Histoenzymologically, the chondrocytes and synovial macrophages showed lysosomal and oxidative enzymatic activity. Immunological assessments (72 sera and 25 synovial fluid samples) showed pathological values of circulating immune complexes, anticollagen antibodies and C reactive protein. Correlation of immunocytomorphological findings demonstrates the involvement of immunologic and enzymatic factors in the pathogenesis of AS.

Morphophysiopathologic studies on the biology of myocardium in acquired valvulopathies.

Myocardial lesions due to various valvulopathies were sampled during open heart surgery under extracorporeal circulation, and histologically, histoenzymologically and ultrastructurally investigated. Various cardiomyocitary and interstitial nonspecific progressive lesions, due especially to hemodynamic and hypoxic alterations, were identified. During the pathogenic stages, we remarked the onset and chronic evolution of perivascular and interstitial oedema, enhanced by a reduced lymph draining. The progressive processes of hyalinization, sclerosis and interstitial fibrosis were subsequent to the interstitial matrix modification. These processes accentuate the myocardial hypoxic lesion due to the nutritional and gaseous exchange alterations. The infrastructure, mitochondrial enzyme equipment, sarcoplasma and tubular network lesions, as well as the intramyocitary oedema that destroys the sarcomeric structure, ended with the activation of lysosome and lysosomal enzymes, giving rise to consequent cytolytic foci. Therefore, the process was extending. In this context, we remarked at the electronmicroscopic examination ventricular natriuremic granules, that are rarely mentioned in literature.

The value of the ultrastructural pattern of myeloperoxidase (MPO), platelet peroxidase (PPO) and acid phosphatase in identification of blastic cell types during acute transformation of chronic myeloproliferative disorders (cMPD).

We established the cell line of bone marrow and blood cells provided by 19 cases of cMPD by ultrastructural studies of their enzymatic content. Myeloblasts, megakaryoblasts and lymphoblasts were identified by the presence of myeloperoxidase, platelet peroxidase and acid phosphatase, respectively.

The value of the ultrastructural pattern of myeloperoxidase and platelet peroxidase in identification of two blastic cell types during transformation of a chronic myeloproliferative disorder.

The value of the ultrastructural pattern of myeloperoxidase (MPO) and plateletperoxidase (PPO) staining is evaluated for the identification of the type of blastic cells during the acute transformation of a chronic myeloproliferative disorder. MPO and PPO are generally accepted as lineage specific markers for the detection of myeloid or megakaryocytic differentiation of the blast cells. The ultrastructural pattern of myeloperoxidase (MPO) and plateletperoxidase (PPO) permitted us to identify two types of blastic cells (one from the myeloid and the other from the megakaryoblastic lineage) in the acute transformation of a chronic myeloproliferative disorders.

Immunocytomorphopathological studies on the pathogenesis of rheumatoid arthritis.

Thirty cases of rheumatoid arthritis were submitted to cytomorphological, histopathological (HE, VG, PAS Alcian, Gömöri, Safranine O), histoenzymological (Acid Phosphatase, chondroitin-sulphatase, Peroxidase) and immunological (rheumatoid factor (RF)) studies; circulating immune complexes, anti-collagen antibodies II, Reactive C protein (CRP), Complementary C3 fraction were also assessed. The synoviocytogram of the rheumatoid synovial fluid (SF) indicated a cytosis with polynucleosis and ragocytosis compared to the hydroarthrosic SF defined by lymphocytosis (47.8%). Enzymologically, especially for high titres of rheumatoid factor, a phosphatase and peroxidase activity was observed in polymorphonuclear cells of a ragocytary type and in phagocytic mononuclear cells. The severe forms of rheumatoid arthritis (RA) were correlated histopathologically with chronic villous synovitis associated with some processes of obliterant vascularitis, fibrosis and sclerosis. At the level of synovio-cartilage junction, fissures and a homogenization of the cartilaginous fundamental substance in the vicinity of disintegrated synovial structures were noticed. Histoenzymologically, a lysosomal and oxidative activity was found in chondrocytes and in synovial macrophages. Immunological assessments (73 serum and 60 synovial fluid samples) showed pathological values of circulating immune complexes, anti-collagen antibodies and C reactive protein. The complementary synovial depletion of the C3 fraction underlines the immune character of the rheumatoid synovitis. The immunocytomorphologic data correlation demonstrates the involvement of immunologic and enzymatic factors in the evolution of Rheumatoid Arthritis.

Apoptosis II: Apoptosis in the pathogenesis and treatment of diseases.

This review presents the implications of abnormal regulation of apoptosis in the pathogenesis of a variety of diseases, some of them characterized by a failure of cells to undergo apoptosis, and the others characterized by cell loss. The new perspectives in the therapy of such diseases by developing therapeutic agents that increase or decrease the susceptibility of particular cells to apoptosis are also reviewed.

Gastrointestinal stromal tumors--a recently defined entity. Literature data and personal case report.

Stromal tumors of the gastrointestinal tract are controverted tumoral entities which were recently delimited. They were initially identified by immunohistochemical investigation and processing of the gastrointestinal muscular tumors and of the malignant and benign nervous tumors. Those investigations were subsequently amplified by electronmicroscopic studies and observations during the patient's prognostic follow-up. Within these circumstances, monoclonal tumors responsive to smooth muscular antigens (actin, SMA), to polyclonal antigens reacting to S-100, PGP 9.5, NSE and GEAP were identified. Thus, tumors with a nervous origin known as a gastrointestinal nerve tumors or plexosarcomas were differentiated, taking into account the difficulty of their distinguishing from gastrointestinal tumors (GIST) which also shows multinucleated great cells. There were also difficulties in defining bidirectionally differentiated tumors or those nonresponsive to any antigen, all these elements proving their origin from nondifferentiated mesenchymal cells. These data are presented in a personal case report of a 28-year old woman with an acute anteroenteral invagination due to a gastrointestinal stromal tumor, favorably removed by surgery and with a postoperative outcome.

Histopathological and ultrastructural modifications of the arthrosis articular cartilage.

Thirty samples of articular cartilage taken during the operation from patients with incipient arthrosis, arthrosis with radiological modifications and arthrosis under study for Rheumatoid Arthritis (RA) were investigated using histopathological (HE, VG, PAS-Alcian, Gömöri, Safranine O) and electronmicroscopic techniques. The control material was made of posttraumatic cartilage (Moore prosthesis). Histopathologically, the incipient arthrosis cartilage had superficial exfoliations associated with reduced saframinophilic tinctorial perichondrocytic activity. The arthrosic cartilage with typical radiological modifications was individualized at the synovia-cartilage junction by villous aspects of the synovia associated with perichondrocytic gaps, reduction of safraninophilia and modifications of reticuline-collagenic network. The arthrosic cartilage under study for RA revealed destructive fibrous modifications of the synovia and severe affection of the articular cartilage at synovia-cartilage junction. Electronmicroscopically, the ultrastructural affection was minimum in the incipient arthrosis cartilage developing to chondrocytic degeneration in arthrosis with radiological correspondent. Both histopathological and ultrastructural data emphasize the fact that arthrosis is associated with synovitis following a primitive degenerative process similar to rheumathoid synovitis in arthrosis under study for RA.

Ultrastructural features in two cases of congenital dyserythropoietic anemia type II.

Two patients with congenital dyserythropoietic anemia (CDA) type II were investigated in bone marrow as well as in blood cells. The majority of red cell precursors showed typical morphological abnormalities: high incidence of binucleated erythroblasts, normoblastic hyperplasia, nucleo-cytoplasmic dissociations, karyorrhexis of some nuclei, presence of synartesis phenomenon, invagination of cytoplasmic portions into the nuclear area and presence of marginal cisterna. The modified erythroblasts were present in the peripheral blood, too. The presence of Gaucher-like cells suggests an abnormal catabolism of the red cell precursors membranes.

Pathogenesis aspects of arthrosis in histopathological and electronmicroscopical studies of articular cartilage, correlated to some immunological parameters.

Twenty-five biopsies of arthrosic cartilage with radiological correspondence, arthro, sic cartilage under study for Rheumatoid Arthritis (RA) and posttrauma cartilage as control-were examined using histopathological (HE, VG, PAS-Alcian, Gömöri, Safranine O) and electronmicroscopical techniques. The arthrosic cartilage with radiological correspondence shows superficial and deep fissures, perichondrocytic gaps and modified reticulino-collagenic network at the histopathological examination. At the level of synovia-cartilage junction, we found some villous aspects of the synovia desquamating in the proximity of the affected cartilage. The investigated arthroses for RA presented some destructive fibrous modifications of the synovia similar to rheumatoid synovitis and associated with some dystrophic chondrocytic alterations. The ultrastructural affection was severe leading to cellular degeneration. The immunologically-studied arthroses for RA had seric pathologic values regarding: circulating immune complexes (CIC) (mean = 67.08 +/- 1.45 U), Ig.M(mean = 358 +/- 3.02 UI/ml) and anti collagen antibodies (mean = 409.9 +/- 0.42 U). The synovial depletion of complementary fraction C3(mean = 42.3-1 mg%) as against the normal seric level (mean = 63.07 +/- 0.49 mg%) suggests an immune synovitis. Correlation of immunomorphopathological data emphasize that arthrosis coexists with a secondary synovitis following a primitive degenerative process and allows arthroses under study for RA to be separated from other degenerative rheumatism diseases.

Histopathological and histoenzimological investigations of the rheumatoid articular cartilage.

Twenty seven biopsies of articular cartilage taken intraoperatively from patients with Rheumatoid arthritis (RA) and from control patients with traumas were examined using histopathological techniques (HE, VG, PAS-Alcian, Gömöri, Safranine 0) and histoenzymological techniques (Acid phosphatase-lysomal marker, Chondroitinsulphatase, Peroxidase). Histopathologically, the rheumatoid articular cartilage appears with superficial and deep cartilaginous fissures, frequent perichondrocytic gaps associated with modification of the tinctorial activity. At the pannus synovia-cartilage junction we found invasive and destructive synovial inflammatory infiltrates penetrating and eroding the cartilage. Histoenzymologically, the rheumatoid chondrocytes have a high lysosomal potential (phosphatasic, chondroitinsulphatasic) and highly oxidative potential (peroxidasic) specific for lesion modifications.

Ultrastructural aspects of megakaryocyte/platelet system in essential thrombocythemia.

Six cases of essential thrombocythemia (ET) have been investigated in bone marrow as well as in blood cells. In majority of the cases, the bone marrow aspirate was hypercellular and presented an increased number of megakaryocytes, some of them with displastic appearance. The ultrastructural pattern of platelet peroxidase permitted us to identify atypic megakaryocytes and megakaryoblasts, particularly when present in pheripheral blood.

Tumoral infiltrate after local treatment with interferon in squamous cell carcinoma.

Using monoclonal antibodies UCHL-1 (T lymphocytes), MT-1 (pan T) and L-26 (B lymphocytes) in the study of the tumoral infiltrate after local treatment with alpha interferon (Roferon) in patients with squamous cell carcinoma of the lower lip, it was observed that: the proportion of UCHL-1 positive cells was between 30% and 80%, the proportion of MT-1 positive cells was of 85% and that of the L-26 positive cells was of 30% of all the cells in the infiltrate. In the area in which after treatment with interferon the tumoral structures had disappeared, the proportion of T lymphocytes was smaller than in the areas in which the tumoral structures were still present. The therapeutic effect of interferon is due both to the direct effects on the tumoral cell and also to the indirect effects, namely the activation of the cytotoxic T lymphocytes and of other cells in the tumoral infiltrate.

Aspects of ankylosing spondylarthritis immunopathogenesis correlated with some immunoseric- and synovial parameters in the investigation of histopathological and electronmicroscopic alterations of the articular cartilage correlated with some immunoseric and synovial parameters.

Eighteen biopsies of articular cartilage taken intraoperatory from patients with Ankylosing Spondylarthritis (AS) and from others with traumatisms (controls) were investigated using histopathological (HE, VG, PAS-Alcian, Gömöri, Safranin 0), electronmicroscopic and histoenzymamologic techniques. Histopathologically, the synovitis in AS is characterized by abundant synovia lymphoplasmocytic infiltrates associated with aspects of vascular hyperplasia and fibrosis. At the pannus synovia-cartilage junction we found the invasive synovia lymphoplasmocytic infiltrates. The proteoglycan (PG) depletion is confirmed histopathologically by diminishing the Safranin 0 staining, then ultrastructurally by the existence of collagen revealing areas, whereas biochemically, by the presence of glycosaminoglycans (GAG) in serum and synovial fluid (SF). The morphological data were related to some immunological parameters involved in pathogenesis. In this way, we found pathological values of the immune circulating complexes (ICC) (serum, mean = 73.5 U; SF mean = 81.80 U) and of anti Collagen II antibodies (serum mean = 410 U; SF mean = 436 U). The reactive protein C acting in the phase (CRP) showed high pathological values both in serum (mean = 5.01 mg%) and in SF (mean = 3.6 mg%) of the patients with AS, emphasizing the inflammatory characteristics of the rheumatic disease. The presence of ICC, anticollagen II antibodies and GAS as well in synovia suggests that the inflammatory articulation in AS is a local potential antigen of collagen and proteoglycan nature.