Transformation of chronic myelogenous leukemia: clinical, morphologic, and cytogenetic features

The morphologic, cytogenetic, and clinical features of 58 patients with transformation of Philadelphia chromosome (Ph1) positive chronic myelogenous leukemia (CML) were evaluated. The patients were divided into two groups on the basis of blood and marrow findings: blast crisis and subacute transformation. The evolution of the leukemic process in 41 patients was classified as blast crisis based on one of three criteria: 30% or more blasts in blood and/or marrow smears, intramedullary focus of blast transformation in a marrow trephine biopsy, or blast transformation in an extramedullary site. The 17 patients with subacute transformation of CML had a deteriorating clinical and hematologic picture but did not manifest any of the criteria for blast crisis. The blood and marrow findings in this group of patients were characterized by several qualitative and quantitative changes, including anemia, thrombocytopenia, decreasing leukocyte count, increasing basophilia, myelofibrosis, dysplastic alterations in hematopoietic cells, and increased blasts which, however, never exceeded 25%. Chromosome abnormalities in addition to the Ph1 were found in 65% of the patients with blast crisis and 86% of the patients with subacute transformation. The 41 patients with blast crisis had a median survival of nine weeks; the 17 with subacute transformation had a median survival of 26 weeks. The shortest median survival for patients with blast crisis, four weeks, occurred in the patients with myeloid blast crisis with chromosome abnormalities in addition to the Ph. The longest median survival, 52 plus weeks, occurred in patients with lymphoid blast crisis with only the Ph1 at transformation.     

椎板下棘的形态学特点及其临床意义

目的：观测椎板下棘的形态特点，探讨其在显微内窥镜腰椎间盘切除术(MED)中的临床意义。方法：对42具成人干燥椎骨和10件脊柱腰骶段标本的椎板下棘进行观测，分析其对椎间管构成的影响；结合MED术式的通道和操作过程，分析其可能导致的并发症。结果：椎板下棘位于椎板下缘前外近椎弓根下切迹处。可出现于所有胸腰椎，出现率为83．3％；出现率最高在第12胸椎，为52．4％。椎板下棘分布不规则，出现在胸腰段较多。结论：椎板下棘是胸腰椎的骨性结构，有必要给予命名；椎板下棘参与构成神经根管的骨性后壁，可造成神经根受压；后路MED可引起椎板下棘断脱，造成神经根受压或损伤。     

Low-grade tubular-mucinous renal neoplasms: morphologic, immunohistochemical, and genetic features.

The current classification system of renal tumors is based on morphologic criteria, as supported by genetic findings. We present a group of previously unclassified tumors with similar morphologic and genetic features, suggesting a new entity within renal neoplasms. Seven renal tumors from five patients (ages 31-67 years) were analyzed. All cases were stained with periodic acid-Schiff, Hale's colloidal iron (HCI), and Alcian blue (AB) at pH 2.5/1.0 with and without hyaluronidase (HA) digestion. Immunohistochemical (IHC) stains were performed for CK8, CK18, CK19, vimentin, villin, Tamm-Horsfall protein (THP), renal cell carcinoma marker (RCC), epithelial membrane antigen (EMA), ulex europaeus agglutinin (UEA-1), soy bean agglutinin (SBA), peanut agglutinin (PNA), and MIB-1. Comparative genomic hybridization (CGH) and loss of heterozygosity (LOH) studies were performed on all cases. All tumors showed circumscribed growth, a tubular growth pattern with focal solid areas, no significant nuclear atypia and absence of necrosis, desmoplasia, or inflammation. Abundant extracellular mucin was present. Immunohistochemistry stains support collecting duct origin (EMA+, PNA+, SBA+/-, CK 8/18/19+, vimentin+/-, UEA-1-, RCC-, villin-, THP-). The proliferative rate was low (<1%). CGH showed multiple consistent chromosomal losses (-1,-4, -6, -8, -9, -13, -14, -15, -22). Clinical outcome was favorable, with recurrences but no known distant metastases or death of disease. These findings are distinct from all previously classified renal neoplasms. Our data suggest the presence of a unique tumor entity within tumors of probable collecting duct origin: tubular-mucinous renal tumors of low malignant potential.     

"Well-differentiated" lymphocytic neoplasms. Immunologic findings correlated with clinical presentation and morphologic features

The authors studied 48 cases of well-differentiated lymphocytic neoplasms using a panel of monoclonal antibodies applied to frozen sections. Forty-seven tumors expressed monotypic immunoglobulin, one or more B-lineage antigens, and Ia (HLA-DR) antigen. Proliferation centers expressed the T9 antigen and increased numbers of Ki-67-positive cells. One tumor was of T-cell origin, had a cytotoxic/suppressor cell phenotype, and showed anomalous loss of Leu-1 antigen. Immunophenotypic findings were correlated to the clinical presentation and morphologic features of each neoplasm. Sixteen tumors were associated with peripheral lymphocytosis (greater than 4000/cu mm), 13 biopsies were obtained from extranodal sites, 16 tumors had proliferation centers, and 11 neoplasms had plasmacytoid features. The authors found no absolute and few statistically significant immunologic differences between the B-cell tumors according to their clinical presentation or morphologic features. Tumors associated with peripheral lymphocytosis more commonly expressed the Leu-1 antigen (P less than 0.01) and IgD (P less than 0.01) and less frequently were stained by BA-2 (P less than 0.05) and OKT9 (P less than 0.05). Plasmacytoid neoplasms more frequently expressed the Tac (P less than 0.01) and T9 antigens (P less than 0.05), and all expressed kappa light chain (P less than 0.05). Extranodal neoplasms more commonly expressed IgM (P less than 0.01). In contrast to the markedly different clinical presentation and morphologic appearance these tumors may have, the immunologic data suggest that B-cell small lymphocytic neoplasms are relatively homogeneous. For an individual case, immunophenotype does not predict clinical presentation or morphologic features.     

Effects of mannitol on the postischemic kidney. Biochemical, functional, and morphologic assessments

To determine the effects of mannitol on the postischemic kidney rats were subjected to 25 minutes of renal artery occlusion and immediately after vascular clamp release they received a 2-ml intravenous mannitol bolus (20%). Equimolar urea-injected rats and sham-injected rats served as controls. Postischemic renal blood flow, tubular metabolic work (renal O2 consumption), adenine nucleotide pools, renal oxidant stress (tissue glutathione, malondialdehyde levels), and tubular cell/mitochondrial swelling (histomorphometry) were assessed at variable times during the early vascular reflow period (15 to 60 minutes). The severity of acute renal failure was determined by serial blood urea nitrogen and serum creatinine studies (24, 48 hours), and by renal histology (48 hours). Mannitol increased postischemic renal blood flow (2-fold), renal O2 consumptions (3-fold), and urine flow compared to urea-injected and sham-injected controls. Postischemic glutathione levels were equally depressed (reduced 33%) in all three treatment groups. Malondialdehyde did not rise. Mannitol significantly lowered total adenine nucleotide content without changing ATP at 15 minutes post renal artery occlusion. At 60 minutes post renal artery occlusion, mannitol- and urea-treated groups had comparable ATP levels, 25% higher than the noninjected controls. Mannitol and urea induced comparable decrements in proximal tubular cell swelling, returning cell volumes to normal values. However, mitochondrial swelling was unabated. Mannitol and urea caused significant and nearly identical degrees of functional and morphologic amelioration of renal injury. Conclusions: Mannitol administered after renal ischemia ameliorates both functional and morphologic aspects of acute tubular injury despite dramatically increasing tubular aerobic work. This protection appears not to be due to early postischemic improvements in adenine nucleotide content, to increased renal blood flow, to increased urine flow, or to a lessening of oxidant stress. The data are consistent with the view that protection results from acute hypertonic solute loading which either directly or indirectly decreases tubular cell but not mitochondrial swelling.     

Proteus syndrome review: molecular,clinical, and pathologic features

Proteus syndrome is caused by an activating AKT1 mutation (c.49G>A, p.Glu17Lys). Many variable features are possible in this mosaic disorder, including: (i) disproportionate, asymmetric, and distorting overgrowth; (ii) bone abnormalities different from those observed in other disorders; (iii) a characteristic cerebriform connective tissue nevus made up of highly collagenized connective tissue; (iv) epidermal nevi in early life, consisting of acanthosis and hyperkeratosis; (v) vascular malformations of the capillary, venous, or lymphatic types; (vi) dysregulated adipose tissue including lipomas, lipohypoplasia, fatty overgrowth, and localized fat deposits; (vii) other unusual features, including bullous lung alterations; specific neoplasms; a facial phenotype associated with intellectual disability and/or seizures, and/or brain malformations; and (viii) deep vein thrombosis, resulting in premature death. Concluding remarks address diagnostic criteria, natural history, management, psychosocial issues, and differential diagnosis.     

3 cases of Alport's syndrome with different clinical and morphologic manifestations

Of 350 renal biopsies referred to the Pathologic Anatomy Department Academy of Medicine in Lód? between 1982 and 1986 the authors recognized three cases of Alport's syndrome. The diagnosis was made on the basis of light microscopy (HE, PTAH, silver staining according to Jones, PAS with alcian blue) and immunofluorescence reactions with the sera against IgA, IgG, IgM and fraction C3 of the complement. In two cases electron microscopy was performed additionally. In two patients clinical data pointed to the diagnosis of Alport's syndrome (hematuria, partial deafness, mental retardation, progressive nephropathy). In the third patient Alport's syndrome was not suspected clinically and the diagnosis was established only on the basis of electron microscopic studies. Light microscopy detected cellular proliferation and increase of the mesangium matrix as well as foci of foamy cells in the renal stroma in one case. Immunofluorescence studies were not significant for the diagnosis whereas electron microscopy examinations were decisive. We found characteristic diffused or focal widening of basal membranes of the glomerular vascular loops with the dense lamina splitting, as well as focal thinning of the basal membranes. The intensity and extent of submicroscopic changes varied in the cases described.     

A syndrome of epilepsy, dementia, and amelogenesis imperfecta: genetic and clinical features.

A family is described with six members affected by a syndrome of epilepsy, dementia, and amelogenesis imperfecta (Kohlschütter's syndrome). An autosomal recessive pattern of inheritance is established for this disorder.     

Phenotypic features of smooth muscle cells during the evolution of experimental carotid artery intimal thickening. Biochemical and morphologic studies

Balloon catheter denudation of rat carotid artery that results in significant medial damage is followed by marked intimal smooth muscle cell (SMC) proliferation associated with limited endothelial regrowth. In this report we demonstrate that: (a) SMC of the carotid media, preceding their intimal proliferation, develop a cytoskeletal profile and morphology consistent with a de-differentiated SMC phenotype; and (b) both medial and intimal SMC subsequently revert to a cytoskeletal profile and morphology reflecting incomplete but significant re-differentiation toward normal SMC phenotype. Specifically, early after balloon injury, SMC of the media and those that have migrated into the intima contain decreased amounts of actin, desmin, and tropomyosin and increased amounts of vimentin; moreover, beta-actin becomes the dominant actin isoform, whereas alpha-actin decreases as compared with that found in normal medial SMC. Late after balloon injury, actin is still less abundant, however, desmin, tropomyosin, and vimentin return toward normal values and both medial and intimal SMC again show a predominance of alpha-actin, although the endothelium does not regenerate over the central surface of intimal thickening in this model. The SMC surface to volume ratio significantly decreases early after balloon injury, whereas it is not significantly different late after balloon injury as compared with that of SMC of the normal carotid media. We demonstrate, furthermore that: (c) adjacent luminal SMC are interconnected by gap junctions and develop focal tight junctions, a feature not reported previously to occur in smooth muscle; these cells however do not form any well defined membrane specialization with the leading edge of endothelium, supporting the view that presence of modified SMC on the luminal surface of chronically denuded vessels is not responsible for the cessation of endothelial regrowth.     

Coffin-Lowry syndrome: clinical and molecular features

The Coffin-Lowry syndrome (CLS) is a rare X linked disorder in which affected males show severe mental retardation with characteristic dysmorphism, most notably affecting the face and hands. The typical facial features consist of a prominent forehead, hypertelorism, a flat nasal bridge, downward sloping palpebral fissures, and a wide mouth with full lips. Mild progression in facial coarsening occurs during childhood and adult life. The hands are broad with soft, stubby, tapering fingers. Other clinical findings include short stature (95%), a pectus deformity (80%), a kyphosis and/or scoliosis (80%), mitral valve dysfunction, and sensorineural hearing loss. The causal gene, RSK2, was identified in 1996 and contains 22 exons which encode a protein of 740 amino acids. Over 75 distinct pathogenic mutations have been identified in 250 unrelated CLS patients.     

The ultrastructural morphologic features of Pittsburgh pneumonia agent.

The fine structure of "Pittsburgh Pneumonia Agent" (PPA) was studied in infected human lung, guinea pig omentum, yolk sac membrane, Vero cell culture, and after cultivation of the organism on buffered charcoal yeast extract agar. The organism is a prokaryotic cell with the general features of a gram-negative bacillus. PPA is ultrastructurally distinctive because of an unusually thick, electron-dense band present within the periplasmic space adjacent to the outer membrane of the cell wall. This band, presumably a mucopeptide (peptidoglycan) layer, was seen in about 95% of organisms in human lung but less frequently under certain conditions of laboratory infection or cultivation. Future studies are required to determine whether this ultrastructural dimorphism of PPA is related to variation in other properties of this bacterium, eg, gram-variability, acid-fastness, colony morphology, and virulence.     

Biochemical features of intrahepatic cholestasis.

A pattern of results is reported which was found to be common among patients who had intrahepatic cholestasis (IHC) which was rarely found in patients with other hepatic conditions. The pattern was recognized from over 1000 cases suspected of hepatobiliary disease. 29 were diagnosed with IHC, and excluding 4, 25 revealed the following etiological pattern: chlorpromazine (12 patients); pregnancy and oral contraceptive use (8); and other (5). As opposed to patients with acute and chronic hepatic disease, IHC sufferers had relatively normal values for immunoglobulins and antibody titers. A disproportionate elevation of serum bilirubin vis-a-vis serum enzymatic activities separated potential IHC cases into intra- and extrahepatic cholestasis. The following factorial evaluations were useful in distinguishing hepatic disease states: 1) when the sum of the activities of serum alkaline phosphatase, 5'-nucleotidase, aspartate and alanine amiotransferases, and isocitrate dehydrogenase was divided by the serum bilirubin concentration, there was good resolution of the distinction between patients with IHC and those with primary biliary cirrhosis, early and late viral hepatitis, cholelithiasis, and pancreatic and bile duct cancers. 2) Resolution was also achieved when the numerator included alkaline phosphatase, 5'-nucleotidase, and aspartate aminotransferase, but not when alkaline phosphatase alone, or alkaline phosphatase combined with 5'-nucleotidase, was used. The essential lesion in IHC is an excretory defect.