Abstract. The chick embryo chorioallantoic membrane (CAM) is commonly used as an experimental in vivo assay to study both angiogenesis and antiangiogenesis in response to tissues, cells or soluble factors. This article summarizes literature data about the use of the CAM in the study of tumor angiogenesis and particularly our experimental data concerning the study of angiogenesis in multiple myeloma and in neuroblastoma.
Keywords: angiogenesis, chorioallantoic membrane, multiple myeloma, neuroblastoma, tumor growth.
Abstract. Introduction. The angiogenesis, the process by which new blood vessels are formed, plays an essential role in the survival of the malignant cells, in the local expansion and tumor invasion, as well as in the appearance of distant metastases. Material and methods. We evaluated the relation between MVD, the VEGF expression, the clinicopathologic factors and the survival in patients with gastric cancer. A prospective study has been carried out, regarding the evolution and aggressiveness of the gastric cancer, with a duration of 5 years, 61 patients that underwent a surgery for gastric cancer being included in the study. The immunohistochemical reactions for CD34 and VEGF were performed for all gastric cancers cases included in the study group. Results. MVD has shown in the gastric carcinomas an average value significantly higher in comparison to the normal mucosa (38.7 vs. 12.5, p<0.001 ES). In the intestinal type we have noticed a much lower average MVD than the average MVD in the diffuse type of gastric carcinomas (36.8 vs. 41.6) (p = 0.02478 S). The anaplastic carcinoma and the signet ring cell carcinoma are detaching themselves as histological forms associated to an intense neoangiogenesis activity. The neoangiogenesis activity is correlated with: the histologic grade, the lymphovascular invasion, the level of extend, the lymph node metastasizing, the distant metastasizing and the TNM stage. The positive immunoreactions for VEGF are significantly more frequent in the gastric carcinomas, in comparison to the normal gastric mucosa (65.6% vs. 6.5%, p<0.001 ES). The immunoreactions to the VEGF protein were positive in 71.1% of the intestinal carcinomas, significantly more frequent in comparison to the diffuse type carcinomas (52.9%) (p = 0.018178 S). Our results show a tight correlation between the histologic grade, the level of the tumor invasion and the VEGF expression. Conclusions. Our results prove the major correlation between the VEGF expression and the 5-year survival rate of the patients with gastric cancer, the survival rate for the carcinomas with VEGF +~++ being significantly lower than for the VEGF negative ones (12.5% vs. 23.8%) (p = 0.027983 S). Our study proves a tight correlation between the VEGF expression and the MVD (p = 0.03986 S), these factors playing an important role in the tumoral biologic conduct, in the progression and the prognostic.
Keywords: gastric cancer, tumor angiogenesis, MVD, VEGF, survival.
Abstract. Many clinical trials revealed that the anti-angiogenic treatment could improve prognosis in patients with metastatic colorectal carcinomas (CRC), when added to standard chemotherapy. In this paper, we tried to find out if the microvascular density (MVD) determined with CD31, CD105 was correlated with lymph node status, and if the intensity of angiogenesis was different in right versus left colon segments. We studied 187 CRC, with and without lymph node metastases, 128 from left and 59 from right colon. Results. In the right colon, the MVD was higher in the cases where the lymph nodes did not present metastases (pN0) but also when four or more lymph nodes were involved (pN2). In the rectum and sigma, the angiogenesis presented the highest intensity in pN0 and pN1 stage (1-3 lymph nodes with metastases), decreasing in pN2 stage. In the descendent colon segment, the MVD did not present differences between the cases with and without lymph node metastases. Conclusions. Our study reveals that the most indicated cases for antiangiogenic treatment seem to be the pN0 and pN1 cases in the rectum and sigma, respectively pN0 and pN2 cases in the right colon. We tend to believe that the angiogenesis intensity in CRC is higher in early-stages of the tumoral proliferation but it is not an increasing process, having rather an oscillating character. Therefore, the angiogenesis remains an independent prognostic and predictive factor and the antiangiogenic treatment is necessary to be individualized for each patient.
Keywords: colorectal carcinoma, lymph node metastases, angiogenesis, immunohistochemistry, antiangiogenic treatment.
Abstract. Myocardial stunning represent a consequence of brief ischemia with reversible regional contractile dysfunction dependent persist from minute to days after reperfusion, despite the absence of irreversible damage and restoration of coronary blood flow. The evolution of these new ischemic entity were described by experimental acute ischemia and repeated intraoperatory myocardial biopsies effectuated near 200 patients with heart disease, excluding those with cardiac failure and atrial fibrillation. Using histological histoenzymological and particularly ultrastructural methods, only reversible mitochondrial and sarcoplasmatic reticulum lesions, slight glycogen granules depletions and sporadical dissociation of myofilaments by edema were seen. Major mechanism for the state was suggested: generation of oxygen derived free radicals with consequent oxidative stress and impaired calcium homeostasis. Rare morphological appearance on stunned myocardium was signaled in the references, our collective first made these studies in Romania.
Keywords: myocardial stunning, experiment, myocardial biopsy, pathogenesis.
Abstract. Many examples of epidermal pseudocarcinomatous proliferations associated to CD30+ lymphoid infiltrates are described in literature. Most of them have been interpreted as epidermal proliferations secondary to the lymphoid infiltrate. In this study, our purpose was to investigate the CD30+ cell population in keratoacanthomas of patients with no other cutaneous or hematological conditions. We randomly selected 21 cases of KA from our archives and performed an immunohistochemical study for CD30 in all of them. The quantity of CD30+ cells was graded according to a 5-tier system (from non-existent to evidence of groups of three or more CD30+ cells each: 0-4). In four cases, the inflammatory infiltrate could not be studied, since the lesions had been enucleated. From the other 17 cases, in 94.12% of them, the infiltrate was graded as 3 or 4. Only one case was graded as 1, and interestingly, this case corresponded to a keratoacanthoma in regression. We also studied the percentage of CD30+ cells in the infiltrate in each case, obtaining a mean of 2.89%. We conclude that CD30+ cells are a common component of the inflammatory infiltrate of normal keratoacanthoma. We also wonder if the cases described as either lymphomas or lymphomatoid papulosis with keratoacanthomatous changes are nothing more but simple keratoacanthomas. Lastly, we see this CD30+ infiltrate as a source of investigation to understand why keratoacanthomas spontaneously regress, instead of progressing to a metastasizing squamous cell carcinoma.
Keywords: keratoacanthoma, CD30, epidermal hyperplasia, lymphomatoid papulosis, anaplastic large cell lymphoma.
Abstract. This paper develops a comparative study between similar subtypes of colonic and rectal adenocarcinoma, based on their immunohistochemical profiles for Ki-67, p53 and bcl-2 markers, in order to evaluate the prediction value for the investigated markers, according to the histologic subtype and location. Thirty cases of adenocarcinoma were investigated, 15 with colonic and 15 with rectal location. For both locations, the cases included five well-differentiated, five moderately differentiated and five low differentiated subtypes. The immunohistochemical investigation was performed using Ki-67, p53 and bcl-2 antibodies (DAKO) and streptavidin-biotin method (LSAB Kit, DAKO). The semiquantitative analysis of the immunohistochemical reactions was based on the Ki-67 and p53 index, respectively, counted as number of positive cells from 100 positive and negative cells. For bcl-2, the reaction was considered positive, respectively negative, for a percentage of positive cells higher, respectively smaller, than 5%. All 30 cases (100%) were positive for Ki-67. The mean value of Ki-67 index for colonic, respectively rectal adenocarcinoma was 55.8%, respectively 59.6%. No statistical correlation was found between the proliferative activity and location (p = 0.502). Ten cases (66%) of colonic adenocarcinoma were positive for p53, with a mean value of 42.5% for p53 index. Eight cases (53%) of rectal adenocarcinoma were positive for p53, with a mean value of 21.1% for p53 index. There was a statistic correlation between the apoptotic activity and location (p = 0.005). The positive reaction for bcl-2 was present in seven (46.6%) and nine (60%) from the 15 cases of colonic and, respectively, rectal adenocarcinoma. The statistic analysis revealed that bcl-2 cannot be significantly associated with any of the two locations (p = 0.48144, 95% CI). The use of the Wald tests permitted the assessment of the predictive power for the investigated markers according to the pathologic subtype and location. Thus, p53 is on the first position (W = 16.56, p = 0.00004, 95% CI), followed by Ki-67 (W = 4.49, p = 0.034, 95% CI), whereas bcl-2 cannot be considered a predictive factor (W = 2.5, p = 0.107, 95% CI). The immunohistochemical evaluation of Ki-67, p53 and bcl-2 yields refined information on colorectal tumor biology. Our study confirms, from the statistic point of view, the role of p53, followed by Ki-67, as predictive factors.
Keywords: colorectal carcinoma, Ki-67, p53, bcl-2.
Abstract. PSA (prostate-specific antigen), a serine protease with chymotrypsin-like activity is the most useful tumor marker for prostate cancer screening, diagnosis, prognosis and monitoring. The identification of PSA in normal and tumoral mammary gland was regarded as a curiosity, but the confirmation of PSA expression in the mammary gland by others teams of researchers and the identification of specific mRNA in tumors with PSA immunoexpression initiated new perspectives for studies. The aim of this study was to examine the prevalence of PSA in breast cancers and to evaluate the correlations between PSA expression and some clinicopathological markers. We analyzed the expression of PSA in series of consecutive breast carcinomas by immunohistochemistry and correlated the PSA expression with the histological type and grade, nodal and metastasis status, estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR) and HER2/neu expression. PSA expression was observed in 44.5% of breast cancers, particularly in lobular types of carcinoma (p<0.0001). In univariate analysis, the expression of PSA was statistically correlated with AR (p<0.0001), PR (p = 0.01) and inversely correlated with HER2/neu overexpression (p = 0.008) and G3 (p = 0.02). PSA did not significantly correlate with ER expression, lymph node and metastasis status. In multivariate analysis, PR was a moderate predictor (p = 0.024) but the lobular type (p = 0.000), AR (p = 0.000), HER2/neu (p = 0.002) and G3 (p = 0.008) were strong predictors for PSA immunoexpression.
Keywords: breast cancer, HER2/neu, prostate-specific antigen, steroid hormone receptors.
Abstract. Angiogenesis, the formation of new blood vessels from a preexisting vascular bed, is a complex multistep process, which may also permit metastasis. To investigate how tumor angiogenesis correlates with tumor histologic type in breast carcinoma diagnosed on core biopsy, microvessels were counted (and graded the density of microvessels) within the initial invasive carcinomas of 155 patients. Using light microscopy, the number of microvessels was counted manually in a subjectively selected hot spot (in the most active areas of neovascularization per 400x field), and their values were separated as above or below median (low and high), without knowledge of the outcome in the patient or any other pertinent variable. When the mean values of MVD of the groups defined by histological type were compared, no significant difference was noted (P = 0.060253). When tumors were classified as high or low MVD, based on a cut-off value (30.70175 microvessels per mm2), cases with high MVD were significantly more numerous. MVD did show a relationship with groups defined by tumor histological type (P = 0.003101). Assessment of tumor angiogenesis may therefore prove valuable in selecting patients with early breast carcinoma for aggressive therapy.
Keywords: angiogenesis, breast carcinoma, histologic type, needle breast core biopsy.
Abstract. In spite of the progresses achieved in surgical treatment, radiotherapy and chemotherapy, the survival rate in oral squamous cell carcinoma (OSCC) remain unchanged among past three decades, which made this neoplasia a major problem of health in the entire world. There were investigated 42 cases of OSCC with different sites and various grades of differentiation, by histological and immunohistochemical techniques (by LSAB/HRP method), using E-cadherine and CD44. Considering the differentiation grade, the cases were histopathologically classified as 9 cases of well-differentiated squamous carcinoma, 14 cases of moderately differentiated squamous carcinoma, and 19 cases of poorly differentiated squamous carcinoma. The E-cadherine immunoexpression study indicated an immunostaining degree 3 in well-differentiated squamous carcinoma, 2 in moderately differentiated squamous carcinoma, and 1 in poorly differentiated squamous carcinoma. The results of CD44 immunostaining indicated in most of the cases an immunostaining degree 2, especially in moderately differentiated OSCC. The immunostaining degree 3 corresponded to nine cases of well-differentiated OSCC, and other two cases of moderately differentiated OSCC. Immunostaining degree 1 corresponded to poorly differentiated OSCC. The results indicate the possibility of using the two-immunohistochemical markers as prognostic factors in OSCC.
Keywords: oral squamous cell carcinoma, E-cadherine, CD44.
Abstract. We realized an ultrastructural study of the cells of the dental pulp, having in view their particularities relative to other types of conjunctive tissue. For this purpose, we selected five cases represented by teeth without subjective or objective symptomatology. Within the paper there are exposed the morphological aspects observed by means of electron microscopy. The results are then discussed in relation with a series of observations made by other researchers regarding the particularities of the pulp cells structures.
Keywords: dental pulp, odontoblasts, dendritic pulp cells.
Abstract. A number of 38 renal biopsies and 13 necroptic pieces removed from 51 prisoners were available for our study. From 51 cases, 21 patients were diagnosed with actual chronic glomerulonephritis, 19 patients with non-specific chronic glomerulonephritis, four patients with renal amyloidosis, and seven patients with glomerulonephritis lesions associated to pielonephritis.
Keywords: locked-up space, glomerular nephropathies, pielonephritis, immunohistochemistry.
Abstract. Squamous cell carcinoma is one of the most frequent cutaneous carcinomas, this neoplasic process inducing cellular and umoral immune response modifications. Our study refers at 60 patients, squamous cell carcinoma diagnosed, at whom we determined IL-2, IL-6 and TNF-alpha, using ELISA technique. The discovered results were different, depending on the differentiation form. The cellular immune response presented important modifications only in poor differentiated form of the disease.
Keywords: squamous cell carcinoma, cytokines, immunohistological correlation.
Abstract. The functional morphology and evolution of the superficial forearm flexor, the palmaris longus, have long fascinated kinesiologists, physical anthropologists and anatomists alike. The anomalies, agenesis, variations and polymorphic presentation of the muscle, coupled with its biomechanical role in the performance of flexion and supination through distal articulations in the upper limb, have formed the base for many studies found in medical literature. We present data from published sources, along with our observations on the kinetics of palmaris longus, drawn from a series of dissections done on 30 cadavers. Complete agenesis was seen in four limbs. Reversal in the muscle-tendon orientation was seen in two limbs and duplication in one limb. The functional dynamics of the muscle and the clinical implication of its modifications in humans are discussed. We believe that every surgeon must be aware of the variations, since this, otherwise unimportant muscle, provides a very useful graft in tendon surgery.
Keywords: palmaris longus, tendon graft, supination, agenesis.
Abstract. A rare case of amelanotic vulvar melanoma is presented. The patient was a 71-year-old woman complaining of vulvar itching and yellowish vaginal discharge who underwent a complete gynecological evaluation during which a suspicious grey-whitish mass on her vulva was observed. The tumor presented superficial ulceration and was located in the upper half of the labia minora and clitoris. Initially it was suspected to be a vulvar carcinoma. A biopsy was taken and a histopathological suspicion of amelanotic melanoma was rendered. The mass was radically excised and the diagnosis was confirmed using HMB-45, Melan-A and anti-S-100 protein antibodies. Malignant melanoma is readily diagnosed by the presence of melanin granules. Although amelanotic melanoma contains a few melanin granules, it is often difficult to differentiate it from other non-epithelial malignant tumors. This report describes a case of amelanotic melanoma of the vulva, which was correctly diagnosed by immunohistochemical staining with the HMB-45, Melan-A antibody and for the S-100 protein.
Keywords: vulvar melanoma, mucosal melanoma, amelanotic melanoma, immunohistochemistry, HMB-45, Melan-A, S-100.
Abstract. Merosin-deficient congenital muscular dystrophy type 1A (MDC1A) is the most common form of congenital muscular dystrophy. MDC1A is caused by mutation of the laminin alpha-2 gene (LAMA2), localized to chromosome 6q22-23. The diagnosis of merosin-deficient CMD is based on the clinical findings of severe congenital hypotonia, weakness, with high blood levels of creatine kinase, WM abnormalities, and dystrophy associated with negative immunostaining of biopsied muscle for merosin. We investigated clinical and laboratory a patient: a girl with merosin-deficient congenital muscular dystrophy type 1A. Clinically the particularity of the case is the association of merosin-negative congenital muscular dystrophy (MN-CMD) with congenital feet deformity. The level of serum creatine kinase is elevated 1045 U/L. Immunohistochemistry show presence of dystrophin, lack of merosin, also the utrophin is normally expressed. Nerve conduction studies are normally, while electromyography suggested a myopathic process with early recruitment and decreased amplitude and duration of response. Magnetic resonance imaging: MRI T1 and MRI T2 show hypointensity and diffuse hyperintensity respectively in the white matter. Supratentorial MRI images showed hypotrophy of the corpus callosum and almost absent cingulate gyrus. In addition, hypophysis is reduced size.
Keywords: congenital dystrophy, LAMA2 gene, merosin, white matter.
Abstract. We report a case of multiple schwannoma in a 63-year-old woman, with histopathological and ultrasound analyses, treated by surgical resection. Our patient presented two masses of ulnar nerve and one mass of superficial fibular nerve, both in the right side of the body. All tumors were encapsulated and the microscopic aspects were represented through two tissue types, cellular tissue (Antoni A) with areas of nuclear palisading (Verocay bodies) and more myxoid, less cellular tissue (Antoni B). A careful clinical examination usually determines the level of involvement without identifying the exact pathology. The tumors were easy to remove without affecting the nerves. Surgical exploration is necessary both as a diagnostic and therapeutic procedure. By presenting this case we wanted to emphasize that presence of schwannoma tumors in the peripheral nerves - ulnar and superficial fibular, and suggest a schwannomatosis case - a rare form of neurofibromatosis (a genetic disorder growths of Schwann cells and other cells that support peripheral nerves), that has only recently been recognized.
Keywords: multiple schwannoma, peripheral nerve, schwannomatosis, sonography.
Abstract. Periorificial lentiginosis, also knew as Peutz-Jeghers Syndrome (PJS), is an autosomally dominant inherited condition determined by a mutation localized at 19p13.3 responsible for mucocutaneous pigmentation and gastrointestinal polyps. Skin- and mucosal pigmentation may be present at birth but usually occur in early childhood, and occasionally may develop later. Round, oval or irregular patches of brown or almost black pigmentation 1 to 5 mm diameter, irregularly distributed over the oral mucosa, gums, hard palate and lips (especially the lower) are observed. The pigmented maculae on the face, encountered especially around the nose and mouth are smaller. Polyps may appear in the stomach, small bowel or colon, with hamartomatous aspects on histology. Acute upper gastrointestinal bleeding and chronic fecal blood loss may appear during the course of disease. There is a higher risk of intestinal and extraintestinal cancers in those patients. We present the case of an 18-year-old young girl accusing since the age of 3 slight intermittent episodes of bloating and abdominal pain without a particular localization, as well as mild iron-deficiency anemia. Physical examination revealed pigmented lesions suggesting PSJ on the palatine and jugal mucosa while endoscopy found a lot of polyps in stomach and a few, isolated in the colon, all having the same hamartomatous pattern. The presence in early infancy of small, well demarcated and dark-brown to blue-black lentigines on the lips, buccal mucosa and perioral skin, should alert the clinician to PJS.
Keywords: hamartoma, gastrointestinal polyps, Peutz-Jeghers syndrome, mucosal lentigines.
Abstract. The anatomical variations of the abdominal arteries are important due to its clinical significance. Various types of vascular anomalies are frequently found in human abdominal viscera, during cadaveric dissection and diagnostic radiological imaging. The present report describes a variation in the celiac trunk as found during routine dissection in a 59-year-old male cadaver. The celiac trunk (CT) was unusually lengthy and took origin from the left antero-lateral surface of the abdominal aorta. Altogether, there were five branches, including three classic branches of CT. The left phrenic artery (LPA) was the first branch of the CT. The remaining four branches were left gastric artery (LGA), splenic artery (SA), common hepatic artery (CHA) and gastroduodenal artery (GDA). There was an arterial loop between the posterior branches of the superior pancreatico-duodenal artery (SPDA), arising from the GDA, and the posterior branch of the inferior pancreatico-duodenal artery (IPDA), arising from the superior mesenteric artery (SMA). The arterial loop formed by the above arteries, supplied the head of the pancreas and duodeno-jejunal flexure. The embryological and clinical significance of above variations has been described.
Keywords: abdominal vessels, celiac trunk, inferior phrenic artery, superior mesenteric artery, pancreatico-duodenal artery, arterial variation.
Abstract. Endometrial stromal sarcoma (ESS) represents a very rare pathological entity occurring as a malignant disease in women genital sphere. Our clinical report is based on a group of four women aged 37, 48, 50 and 70-year-old, that have been histologically diagnosed with endometrial stromal sarcoma. The most common symptom sending the patient to the physician has been the vaginal bleeding, occurring in all patients. Other associated symptoms were the abdominal enlargement and the presence of the pelviabdominal mass generated by the tumor, low to medium abdominal pain or polakiuria. Two patients were diagnosed with ESS after accomplishing a biopsic curettage of the uterus. Total abdominal hysterectomy and salpingo-oophorectomy have been successfully performed for all of the patients. Adjuvant therapy - radiotherapy has been administered to three patients. At this time, none of the patients died of the disease. Our paper also includes a concise review of the literature in order to have an up-to-date conception regarding diagnosis, therapy and outcome for ESS.
Keywords: sarcoma, pathology, therapy, outcome.
Abstract. The present study examines the gross anatomical features of anomalous lunate sulcus detected incidentally in a cadaveric brain and discusses its clinical importance. The absence of lunate sulcus was carefully studied in a dissected brain specimen. The absence of lunate sulcus was observed unilaterally on the right side of a cadaveric brain specimen. The lunate sulcus was clearly appreciated on the left side whilst on the right side it was absent. The right hemisphere of the cerebellum was also bigger in size as compared to the left. The absence of lunate sulcus is a rare finding, which may be detected incidentally. The anatomical knowledge of the lunate sulcus may be important for neurosurgeons operating on the occipital lobe and the radiologists interpreting CT scan.
Keywords: lunate, sulcus, gyrus, occipital, lobe, brain, anatomy, anomaly, variation.
Abstract. Dural metastasis (pachimeningeal carcinomatosis) refers to involvement of dura mater and subdural or epidural spaces in systemic cancer. Although dural metastasis are relatively frequent in malignancies, (8-9% of patients with advanced systemic cancer in autopsy), they are rarely associated with subdural hematoma. We present the case of a 66-year-old male, refereed to the hematological unit for severe anemia of unknown cause and diagnosed as acute myeloid leukemia, developed in the 10th day from admission progressive gait disorders with marked imbalance and mental status change. A CT head scan showed a large, chronic subdural hematoma, which was surgically removed. Pathological examination of the dura and citological examination of the subdural fluid revealed metastatic involvement of the dura, demonstrating the association of dural metastasis and chronic subdural hematoma.
Keywords: dural metastasis, subdural hematoma.
Abstract. Joseph Babinski (1857-1932), a French neurologist of Polish origin, médecin des hôpitaux de Paris, is well known for the discovery of the Sign (the toes phenomenon) which bears his name. Beyond the Sign, his semiological work in the field of neurology is also important (particularly cutaneous and osteo-tendinous reflexes, cerebellar and vestibular semiology, hysteria and pithiatism) as well as his role in the birth of the French neurosurgery. On the contrary, the implication of Babinski in pathological anatomy and histology is usually unrecognized. However, in the beginning of his career, Babinski worked as an Interne in the clinical departments of Victor Cornil (1837-1908), professor of pathological anatomy and president of the Société d'Anatomie de Paris, Alfred Vulpian (1826-1887), past professor of pathological anatomy and then professor of experimental physiology, and in the laboratory of Louis Ranvier (1835-1922), professor of general anatomy at the Collège de France. Babinski beacame préparateur at the chair of pathological anatomy, member then treasurer of the Société Anatomique, member of the Société de Biologie. He reported on several clinico-pathological observations of general pathology (liver cirrhosis, cancer of the kidney, cancer of a buttock, squamous epithelioma, tuberculosis, multiple cysts of the liver and the kidneys, bowel occlusion), of neuropathology (embolic brain softenings, hydatic cysts of the brain, multiple sclerosis, spinal cord combined sclerosis, tabetic arthropathies, adiposo-genital syndrome due to a pituitary tumor) and of human neuro-muscular histology (neuro-muscular spindles, muscular histology after nerve sectioning, diphtheria paralysis, peripheral neuritis).
Keywords: History of Medicine, Histology, Pathological Anatomy, Babinski.