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Langerhans cells in squamous exocervical carcinoma: a quantitative and ultrastructural study.

The gross morphology, density, distribution, and ultrastructure of the Langerhans cell (LC) in the human exocervix in cases of cervical intraepithelial neoplasia (CIN) and incipient carcinoma were investigated. Two zinc-iodide-osmium (ZIO) procedures were applied to epithelial sheets and to tissue sections for light and electron microscopy. The ZIO methods as well as conventional electron microscopy revealed the presence of LCs in CIN, in the invasive prongs, and in the lymphoid infiltrate of the chorion. The epithelial sheets demonstrated a LC density 3.5 times higher than we have previously reported for the normal exocervix. The region around the external os displayed the highest LC density and the most advanced grades of CIN. The LCs were classified into six types according to the number of processes and secondary branches. The most ramified types were more abundant in the neoplastic exocervix than in the normal exocervix. The LC in all locations of the exocervix with carcinoma showed hypertrophy of the rough and smooth endoplasmic reticula and a large number of filaments. The RER displayed dilated cisternae containing electron-dense material. Specialized contacts between LCs and lymphocytes were an outstanding finding. These findings suggest that the LC might play an important role in the neoplastic process.

Adult↗

[Is it useful to correct the immunological deficit in cancer patients? And with what modality?].

A certain degree of immunodepression appears to be present in some neoplastic patients. Many factors such as age and nutritional and hormonal state (particularly thymic factors and locally-acting hormones like prostaglandins of E series) are involved in this phenomenon. The literature shows that all these factors are very important in neoplastic processes and might strikingly contribute also to the extent of immunodepression observed in neoplastic patients. Moreover, the HLA genotype seems to effect the efficiency of the antineoplastic treatments. The authors think that immunodepression in neoplastic patients might be improved by immunomodulators such as zinc ions, thymic hormones and, possibly, inhibitors of prostaglandins of E series.

HLA Antigens↗

[Exposure to asbestos and levels of selected tumor biomarkers].

Occupational exposure to asbestos, a recognised carcinogen, poses a risk for such diseases as asbestosis, lung cancer and mesothelioma. It is thought that asbestos fibres may damage microphages which undergo neoplastic transformation as well as fibroblast, while partial phagocytosis may generate free oxygenic radicals which induce cellular peroxidase and damage macromolecules. A search for cellular changes or changes in cellular metabolism products, present in biological fluids, in order to detect early stages of a neoplastic process is an important factor in the prophylaxis of workers exposed to asbestos. Neoplastic biomarkers such as tissue polypeptide antigen (TPA) or carcinoembryonic antigen (CEA) are now used for this purpose. The aim of the work was to identify workers exposed to asbestos in the population, especially high risk groups neoplastic diseases and to evaluate the usefulness of TPA and CEA determinations. The study covered a group of asbestos exposed workers (n = 4000 and the control group of workers (n = 135) nonexposed to any toxic factor at work. Age, exposure time, smoking habits and workpost characteristics were taken into consideration in the analysis of the results. It was revealed that in 38 persons exposed to asbestos, TPA values were above the concentration limit set on the basis of studies carried out in the control group, and elevated CEA values applied to 13 persons. Significant differences between groups under study were found in the proportion of pathological TPA values. Such a relationship was not observed in regard to CEA values. In the exposed group the results also indicated an evident effect of age and exposure time on the number of persons with TPA values above concentration limit. There is a growing tendency in those changes but only in regard to TPA values. The effect of smoking on the frequency of pathological TPA values was also clear-cut in workers exposed to asbestos. Taking into account three types of employment: blue collar workers, white collar workers and other personnel, the analysis indicated significant differences in TPA values between blue collar workers and other personnel; and between white collar workers and other personnel. This means a similar percentage of pathological TPA values in the group of blue collar and white collar workers. The study carried out allowed to identify persons exposed to asbestos who should be covered with targeted medical care. They also proved that TPA biomarker is better than CEA one for this kind of studies.

Adult↗

Studies on pulmonary tissue after administration of mutein VI-HREC TNF-alpha into implantable experimental Morris hepatoma.

Experiments were carried out on Buffalo rats with implantable Morris hepatoma 5123 growing in the skeletal muscles of the limbs. Mutein VI (a protein which differs from the native TNF-alpha molecule in its N-terminal amino acid composition) was administered at a dose of 10 micrograms per rat once a day in a cycle of 8 days. Control animals were given saline (PBS). Ultrastructural changes within the pulmonary tissue were evaluated with an electron transmission microscope (TEM), with special attention paid to endothelial cells and alveolar epithelial cells. Quantitative analysis of neoplastic metastases to the lungs was carried out. The animals given mutein VI compared to those injected with PBS demonstrated a decrease in the number of metastases. TEM pictures showed accumulations of eosinophilic granulocytes and monocytes in the lumen of the blood vessels. Enhanced activity of endothelial cells was observed. In pulmonary alveoli conglomerates of fibrin, and fragments of damaged cells were found, with erythrocytes, granulocytes and macrophages in their vicinity. The epithelium of pulmonary alveoli showed signs of considerable damage, including necrosis. The mutein VI-hrec TNF-alpha was found to block the neoplastic process, illustrated by a reduction in the volume of lung parenchyma occupied by neoplastic metastases. Also, the ultrastructural changes observed in the pulmonary tissue indicate the possibility of peripheral action of mutein VI after its administration to rats carrying the Morris hepatoma.

Animals↗

Embolization and serum lysozyme activity in renal cancer.

The aim of the study was to determine the effect of renal tumor embolization on nonspecific immunity by evaluating lysozyme activity and leucocytosis in 45 patients and 40 healthy people. Lysozyme activity was assessed in the non-diluted serum (A1) and in the tenfold diluted serum (B1) prior to embolization and after embolization (A2, B2) and in control group. Prior to embolization, lysozyme activity was lower in the experimental group (A1 and B1), compared to the control groups, the differences being statistically significant (p < 0.05). After embolization, the activity became normalized (A2), reaching the control value and even exceeding it (C) in the diluted serum (B2). Leucocytosis prior to embolization (L1) resembled that of control group, increasing slightly after embolization (L2). The differences observed in the changes in lysozyme activity and leucocytosis were statistically significant (p < 0.05). Our findings indicate an inhibitory effect of the neoplastic process on nonspecific immunity. Embolization causes ischemic necrosis of tumor and products of neoplastic tissue disintegration exert a stimulating effect on granulopoiesis, by increasing the turnover of neutrophilic granulocytes. Granulocytic-monocytic infiltrations in tumor stroma are the source of lysozyme, enhancing not only local but also systemic immunity, which is manifested in the increased lysozyme activity in blood serum.

Adult↗

Intraepithelial and postinvasive neoplasia as a stochastic continuum of clonal evolution, and its relationship to mechanisms of chemopreventive drug action.

The progression of intraepithelial and postinvasive neoplasia depends on the occurrence of clonal evolution, defined as the continuous development of mutations and selective clonal expansions in the neoplastic cell population. The two continuously repeating events of clonal evolution, mutation and clonal expansion, occur at unpredictable times and locations. Therefore the neoplastic process is best characterized as a stochastic, i.e., probabilistic, continuum. The rate of intraepithelial neoplastic progression is continuously driven by the dosage level of exposure to mutagens and mitogens. For example, in chronic smokers the length of time before development of lung cancer depends on the number of cigarettes smoked per day. A commonly held misconception is that human carcinogenesis develops after an initial short period of mutation followed by a long period of stimulated proliferation (the multistage model). This incorrect idea derives from the sequential nature of the consecutive two- or three-step operational protocols imposed on experimental animal models by the experimenter. In reality, human carcinogenesis develops as the result of simultaneous and continuous exposure to mutagens and mitogens over the entire period of tumor development. A recent example is the finding that the intraepithelial neoplasia of colorectal adenomas continuously progresses through serial waves of mutation and clonal expansion. The rational design of chemopreventive agents should be based on blocking the two parameters which continuously drive neoplasia: mutagenesis and mitogenesis. In addition to blocking exposure, chemopreventive agents may act at many points during activation and DNA adduction of mutagens, or during stimulation of the proliferation signal pathway by mitogens. Based on the chemopreventive strategy of blocking mutagenesis and mitogenesis, chemopreventive agents are classed as either antimutagenic or antimitogenic. A third class, the antioxidants, are both antimutagenic and antimitogenic, and operate by the common mechanism of breaking free radical chain reactions initiated by reactive oxygen species. In the program of the Chemoprevention Investigational Studies Branch, Division of Cancer Prevention and Control, National Cancer Institute, preclinical development of antimutagens, antimitogens, and antioxidants is well under way, and some of these agents are highlighted here.

Antioxidants↗

Macrophage activation syndrome: an autopsy case of sudden death.

In a context of viral gastroenteritis, we report an unusual case of sudden death in an 8-year-old child. The only macroscopic abnormality observed in the autopsy was a diffuse mesenteric adenitis. Organ samples were taken for histopathological examination and a diffuse lymphocytic infiltration was observed. A sinusoidal histiocytic hyperplasia was found in the lymph nodes. Microscopic examination of the lungs and the lymph nodes revealed haemophagocytic lesions (lymphocytes within the cytoplasm of histiocytic macrophages). Immunohistochemical studies demonstrated that the histiocytes were CD68+ PS100- CD1A-. Following this microscopic examination macrophage activation or haemophagocytic syndrome was diagnosed. The syndrome is a distinct clinical entity characterised by fever, pancytopaenia, splenomegaly, and haemophagocytosis in the bone marrow, liver and lymph nodes. It is a clinical entity that is very difficult to diagnose due to the lack of specific clinical signs. It is generally a complication of an infectious process, an aggravation of an auto-immune disease or a complication of a neoplastic process. The physiopathology involves a disregulation of T lymphocytes and particularly T helper lymphocytes. To make this diagnosis the anatomopathological examination must be performed by an experienced practitioner. The presence of a lymphocyte infiltrate of macrophagic histiocytes in myeloid organs and especially positive CD68+ immune markers are the anatomopathological proofs of diagnosis. The autopsy examination must be carefully performed and include systematic sample harvesting for anatomopathological examination. The results of all these examinations taken together allow the diagnosis of haemophagocytic syndrome to be finally made.

Autopsy↗

New structural chromosomal rearrangements in congenital leukemia.

The karyotypic abnormalities and clinical data on three patients in whom acute leukemia was diagnosed within the first 6 months of life are presented. The four structural chromosomal rearrangements detected in the bone marrow from these patients, i.e., t(7;12)(q36;p13) and t(1;19)(q11;q11) in case 1, t(2;10;11;12)(q21q31;p13;q13;q24) in case 2, and t(11;19)(q23;p13) in case 3, have not previously been associated with congenital leukemia. Acquired chromosomal changes have until now been reported in only 31 leukemic infants in this age group. Of the total material, 18 patients had acute lymphoblastic leukemia and 16 had acute nonlymphocytic leukemia. The by far most frequently recorded cytogenetic aberration has been t(4q;11q), seen in 14 cases of lymphoblastic leukemia. Although t(4q;11q) has not been found in a single patient with acute nonlymphocytic leukemia, these leukemias have often had other rearrangements involving the same region of 11q. Hence, genetic material around 4q21 may be active in lymphocytic differentiation, whereas gene(s) in 11q23 may be important in the neoplastic process in a less cell-type specific manner and perhaps particularly vulnerable to neoplastic rearrangement in fetal life. The finding of four cases out of 34 with translocations between 11q23 and chromosome 19 indicates that this rearrangement might characterize a specific cytogenetic subgroup of leukemia in the very young.

Acute Disease↗

Cytological diagnosis of primary leiomyosarcoma of bone: case report.

We report on a case of primary leiomyosarcoma of the bone in a 77-yr-old man. The patient presented with a painful, enlarging mass in the left shoulder of 6 mo duration. Radiography and computed tomography (CT) revealed a large destructive intramedullary lesion of the proximal humerus, with massive extension into the surrounding soft tissues. CT-guided fine-needle aspiration biopsies (FNAB) of both the bony and soft-tissue lesions were performed. Cytological examination showed a neoplastic process composed of spindle cells mixed with pleomorphic cells. The smooth muscle origin of the neoplastic cells was confirmed by immunocytochemical analysis. We describe the cytological features of this rare primary tumor of bone, and consider the differential diagnosis of spindle-cell neoplasms.

Aged↗

Reduced connexin 43 expression in high grade, human prostatic adenocarcinoma cells.

Gap junction-mediated communication is required for normal cellular growth and differentiation. As cancer is thought to be a manifestation of the breakdown of cell-cell communication, with the concomitant loss of growth control, it would be expected that alterations in the primary structure, processing, oligomerization or trafficking of connexin (cxn) molecules would have a profound effect on the neoplastic process. Here we a present a preliminary immunohistochemical and molecular analysis of cxn 43 expression in prostatic epithelial cells from resected human tissue. Our data indicate that benign prostatic epithelial cells express cxn 43 protein, but that this expression is diminished in more advanced, anaplastic cancer cells. These data suggest that decreased connexin expression is not involved in the initiation of prostate cancer, but rather occurs during the progression of the disease.

Adenocarcinoma↗

Collagenous fibroma (desmoplastic fibroblastoma): a clinicopathologic analysis of 63 cases of a distinctive soft tissue lesion with stellate-shaped fibroblasts.

Sixty-three cases of collagenous fibroma (desmoplastic fibroblastoma) from the files of the Armed Forces Institute of Pathology were analyzed. These tumors occurred mostly in men (80%) with a median age of 50 years (range, 16 to 81 years). The lesions had a wide anatomic distribution and involved the arm (24%), shoulder girdle (19%), posterior neck or upper back (14%), feet or ankles (14%), leg (14%), hand (8%), and abdominal wall and hip (6%). The patients typically presented with a history of a painless, slowly growing mass, often of relatively long duration. The tumors ranged in size from 1 to 20 cm (median, 3.0 cm). The lesions were predominantly subcutaneous, but fascial involvement was common, and 27% of cases involved skeletal muscle. Gross examination typically showed an elongated, lobulated, or disc-shaped mass with a firm consistency and a homogeneous pearl-gray color. Histologically, the tumors often appeared well marginated on low-power examination, but most (78%) infiltrated fat or, less commonly, skeletal muscle. The lesional cells were relatively bland stellate and spindle-shaped fibroblasts separated by a collagenous or myxocollagenous matrix. Mitotic activity was absent or minimal. Some of the lesional cells had a myofibroblastic immunophenotype, as evidenced by focal reactivity for muscle-specific and alpha-smooth muscle actins. In a few cases, rare actin-positive cells were also positive for keratins. Desmin, S100 protein, and CD34 were not expressed. None of the 39 patients with follow-up (median, 11 years) developed a recurrence. Collagenous fibroma is a benign fibroblastic/myofibroblastic proliferation. The large size of some of these tumors coupled with slow growth and persistence favors a neoplastic process over a peculiar reactive proliferation. The differential diagnosis includes a variety of reactive and neoplastic fibroblastic lesions, most importantly fibromatosis and low-grade fibromyxoid sarcoma. Simple, conservative excision is the treatment of choice for collagenous fibroma.

Adolescent↗

Trauma-induced aneurysmal bone cysts in two psittacine species (Cacatua alba and Nymphicus hollandicus).

An umbrella cockatoo (Cacatua alba) and two cockatiels (Nymphicus hollandicus) were presented with rapidly enlarging masses of the head or wing joints. Historic trauma to these areas was confirmed in two cases. All birds were >2 yr of age, and two were female. Cytologic examination of fluid aspirated from masses in two cases was described as serosanguineous cytologically but failed to reveal inflammation, neoplasia, or microorganisms. Radiographic evaluation of these masses included proliferation and lysis of bone, suggestive of a neoplastic process. Histopathologic examination of surgically excised tissues revealed proliferative new bone and an absence of neoplastic tissue in all cases, consistent with aneurysmal bone cyst formation. Despite the guarded prognosis reported for other companion animals, these case results suggest a good prognosis for aneurysmal bone cyst in psittaciformes. Complete surgical excision and histopathologic examination is recommended for definitive diagnoses of aneurysmal bone cyst. Postoperative bandaging and rational antibiotic use are indicated to prevent excessive motion and secondary infection of affected sites, respectively.

Animals↗

[Carbon granuloma--an unwanted effect of laryngeal laser microsurgery].

Over recent twenty years, laser microsurgery has gained great recognition in the treatment of early carcinoma. From 1990 to 2004, more than 800 operations on the larynx were performed using laser microsurgery, including 167 chordectomies for squamous cell carcinoma. In 14 patients who were on the follow-up for 1 to 6 months, we observed a spherical, smooth structure (3-5 mm in diameter) in the middle part of the scar, which imitated local relapse of the neoplastic process. The lesion was removed with CO2 laser. Histopathologic examination revealed, in all cases, the presence of nonspecific, inflammatory process and development of granulation tissue. In only one patient in further follow-up, neoplastic growth recurred. Such lesions were not observed in other than chordectomy laser microsurgical procedures.

Carbon↗

[Peritoneal implants in patients affected by chronic renal failure in hemodialysis programme].

The presence of peritoneal implants detected by computered axial tomography (CT) is usually related to mesothelial primary neoformative processes or, more frequently to peritoneal metastasis or peritoneal carcinomatosis. Although the higher prevalence of neoplastic processes in the chronic renal failure population, the association of peritoneal implants and constitutional syndrome is not always correlated to peritoneal carcinomatosis. We present the case of two patients with chronic renal failure in hemodialysis programme, with abdominal insidious clinical, constitutional syndrome and similar peritoneal implants seen by CAT: the histologic analysis of peritoneal implants gave the definitive diagnostic of secondary amyloidosis and peritoneal tuberculosis respectively.

Adult↗

[Bone marrow reconversion and magnetic resonance imaging: case report].

INTRODUCTION: Bone marrow is divided into red marrow mainly constituted of hemopoietic cells and fatty yellow marrow. In some situations, yellow marrow may be converted into red marrow and this process is called marrow reconversion. Magnetic resonance imaging may be misleading with an invading bone marrow neoplastic process. EXEGESIS: We report a patient with non-Hodgkin's lymphoma with vertebral invasion. Clinical features at presentation were misleading with lower limbs migratory pain suggestive of inflammatory myositis. An MRI study of thigh muscles revealed femoral nodular lesions suggestive of bone marrow reconversion. CONCLUSION: Bone marrow reconversion is a physiologic and reversible process. Awareness of its radiographic features may help to avoid a diagnostic biopsy procedure.

Adult↗

Relevance of folate metabolism in the pathogenesis of colorectal cancer.

The purpose of this review is to outline the principal mechanisms involved in folate metabolism and how they may relate to the pathogenesis of colorectal cancer (CRC). In recent years, mild folate depletion (low normal level) has been associated with an increased risk of developing certain cancers, in particular colorectal neoplasia. The epidemiologic and mechanistic evidence linking folate deficiency with carcinogenesis is reviewed, with a particular emphasis on colorectal neoplasia. Methylenetetrahydrofolate reductase (MTHFR) is a critical folate metabolizing enzyme, and a functional polymorphic variant of this enzyme, the so-called thermolabile variant, caused by a C677T transition in the MTHFR gene, is common in the general population. This review critically examines the evidence that suggests that carriers of this C677T variant may be at increased risk of developing colorectal neoplasia. Although folate depletion may predispose to the initiation of the neoplastic process, folate supplementation, on the other hand, might potentiate the progression of an already established early neoplastic clone (eg, a colorectal adenoma). This could have potential public health implications, given an increasingly widespread policy of folate supplementation of food staples.

Adenoma↗

75Se-sodium selenite as a diagnostic aid in the assessment of peripheral pulmonary opacities.

To establish or exclude the diagnosis of bronchial carcinoma a series of 43 patients with peripheral pulmonary opacities was studied by lung scanning after intravenous injection of 75Se-sodium selenite. A diagnosis was ultimately obtained in all patients. The incidence of both false-positive and false-negative results was high. Selenite was taken up by a range of non-neoplastic processes including inflammatory lesions. The value of the procedure in distinguishing bronchial carcinoma from non-neoplastic conditions of the lung that radiographically mimic carcinoma was not confirmed.

Adult↗

[Clinical and therapeutic profile of broncho-pulmonary adenocarcinomas].

Broncho-pulmonary adenocarcinoma get interest since many years because his increased prevalence. Between december 1998 and January 70 male patients, mean age 56 years, with broncho-pulmonary adenocarcinome were collected retrospectively. The epidémiologic, clinic, radiologic and evolutive data of this pathologic form of cancer was studied. The ratio increased from 10% in 1988 to 14% in 1996. Clinic manifestations was common. Radiologic features was represented essentially by a unique (82%) and péripheric (56%) opacity. The diagnosis, based on cytologic and histologic data, was assessed in 39% of cases by endoscopic biopsy. The investigation for the primitive neoplasic process was made in 18% of patients and found only 2 cases of extra-pulmonary neoplastic process. Curative treatment based on surgery is performed only in 28% of our patients regarding the advanced stage of disease explaining the low survival rates.

Adenocarcinoma↗