[Use of magnesium for prevention of pain in vasospastic angina in a patient with recurrent myocardial infarction; pathogenesis of vasospasm].
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Angina Pectoris, Variant↗
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Clear cell meningioma, an uncommon variant of meningioma: a clinicopathologic study of nine cases.
AIMS: Clear cell meningioma (CCM) is an uncommon variant of meningioma, which affect younger patients, occur more often in spinal or cerebello pontine locations and shows a higher recurrence rate. Only few case reports have been described in the literature. The study has been undertaken to document the clinicopathological features of nine cases of CCM, operated at All India Institute of Medical Sciences during 1998 to December 2005. METHODS: Clinical information was retrieved from the records of our Neurosurgery Department. The cases were stained with H&E, periodic Acid Schiff (PAS) with and without diastase. Immunohistochemistry for pancytokeratin, epithelial membrane antigen, vimentin, glial fibrillary acidic protein, and MIB-1 was done in all cases. RESULTS: During a period of 8 years, nine cases of CCM were diagnosed. Age ranged from 10 to 65 years (median age 26.0 years) with female predominance. Most common location was posterior fossa (CP angle). Clinically most of the patients presented with history of headache and features of cranial nerve palsies. The duration of symptoms varied from 3 to 60 months (mean 16.7 and median of 4 months). Radiologically lesions showed homogenous enhancement and were isointense to brain parenchyma. Histopathologic examination revealed tumor cells to be arranged in sheets with clear cytoplasm and monomorphic nuclei. MIB-1 labeling index (LI) ranged from 2 to 12% with a mean of 9%. Follow up varied from 3 to 84 months (median 36 months) and recurrence was noted in two patients after 2 and 3 years of surgery, respectively, despite their low MIB-1 labeling indices. CONCLUSIONS: CCM is a rare variant of meningioma with poor outcome. Less than 50 cases have been described in the literature. Low rate of recurrence and recurrence despite their low MIB-1 LI are some of the features, which needs to be documented. Hence, larger number of cases with adequate follow-up data need to be studied further to establish the clinical significance of this variant.
Adolescent↗
Elevated white cell count in acute coronary syndromes: relationship to variants in inflammatory and thrombotic genes.
BACKGROUND: Elevated white blood cell counts (WBC) in acute coronary syndromes (ACS) increase the risk of recurrent events, but it is not known if this is exacerbated by pro-inflammatory factors. We sought to identify whether pro-inflammatory genetic variants contributed to alterations in WBC and C-reactive protein (CRP) in an ACS population. METHODS: WBC and genotype of interleukin 6 (IL-6 G-174C) and of interleukin-1 receptor antagonist (IL1RN intronic repeat polymorphism) were investigated in 732 Caucasian patients with ACS in the OPUS-TIMI-16 trial. Samples for measurement of WBC and inflammatory factors were taken at baseline, i.e. Within 72 hours of an acute myocardial infarction or an unstable angina event. RESULTS: An increased white blood cell count (WBC) was associated with an increased C-reactive protein (r = 0.23, p < 0.001) and there was also a positive correlation between levels of beta-fibrinogen and C-reactive protein (r = 0.42, p < 0.0001). IL1RN and IL6 genotypes had no significant impact upon WBC. The difference in median WBC between the two homozygote IL6 genotypes was 0.21/mm3 (95% CI = -0.41, 0.77), and -0.03/mm3 (95% CI = -0.55, 0.86) for IL1RN. Moreover, the composite endpoint was not significantly affected by an interaction between WBC and the IL1 (p = 0.61) or IL6 (p = 0.48) genotype. CONCLUSIONS: Cytokine pro-inflammatory genetic variants do not influence the increased inflammatory profile of ACS patients.
Acute Disease↗
Cytogenetic changes in rat tracheal epithelial cells during early stages of carcinogen-induced neoplastic progression.
The cytogenetic changes in enhanced growth (EG) variants of rat tracheal epithelial cells in culture were examined. These variants which are detectable at 35 days after carcinogen exposure are the first phenotypic alteration in the multistep neoplastic process studied in this model system. Karyotypic analysis of N-methyl-N'-nitro-N-nitrosoguanidine-induced EG variants at Day 35 was made possible by the development of an in situ method of cytogenetic analysis on intact colonies containing too few cells for conventional chromosome preparation methods. Of the transformed EG variant colonies in both control and N-methyl-N'-nitro-N-nitrosoguanidine-treated groups, 62-78% had abnormal karyotypes which included numerical and structural changes. There were no specific chromosome changes, although aberrations of chromosomes 3 and 4 were recurrently observed. However, some colonies of even the most morphologically transformed EG variants were composed of only diploid cells. To confirm this finding 10 EG variant colonies were bisected and half of the clone was prepared for chromosome analysis and the other half was subcultured to measure the clonogenicity and karyotypes of the cells. Cells from 3 colonies plated very poorly on 3T3 feeders and therefore no karyotypic analysis of the colony-forming cells was possible; the cells of the 3 parental colonies were diploid. Three other parental colonies were predominantly diploid (80-90%) but upon replating the resultant daughter colonies had progressively smaller fractions of diploid cells indicating a selection for cells with abnormal karyotypes. When more selective conditions were used (i.e., growth after removal of the feeder cells), the percentage of abnormal cells increased even further. In one case the parental cells had a karyotypic alteration in the long arm of chromosome 4 and this karyotypic alteration was accentuated in the daughter colonies. Thus, selection of cells with increased growth ability upon subculturing or growth in the absence of feeder cells (properties associated with the acquisition of immortality) resulted in concomitant selection for cells with abnormal karyotypes. Since some of the carcinogen-induced rat tracheal epithelial cells expressing the EG variant phenotype were diploid, it is possible that the first step in this transformation process is an epigenetic change. However, most of the diploid cells became terminal. The aneuploid subpopulations present in these colonies have a selective growth advantage and comprise the cell compartment that expresses continued growth, immortality, and ultimately tumorigenicity.
Aneuploidy↗
Molecular analysis of the eighteen most frequent mutations in the BRCA1 gene in 63 Chilean breast cancer families.
BRCA1 gene mutations account for nearly all families with multiple cases of both early onset breast and/or ovarian cancer and about 30% of hereditary breast cancer. Although to date more than 1,237 distinct mutations, polymorphisms, and variants have been described, several mutations have been found to be recurrent in this gene. We have analyzed 63 Chilean breast/ovarian cancer families for eighteen frequent BRCA1 mutations. The analysis of the five exons and two introns in which these mutations are located was made using mismatch PCR assay, ASO hybridization assay, restriction fragment analysis, allele specific PCR assay and direct sequentiation techniques. Two BRCA1 mutations (185delAG and C61G) and one variant of unknown significance (E1250K) were found in four of these families. Also, a new mutation (4185delCAAG) and one previously described polymorphism (E1038G) were found in two other families. The 185delAG was found in a 3.17% of the families and the others were present only in one of the families of this cohort. Therefore these mutations are not prominent in the Chilean population. The variant of unknown significance and the polymorphism detected could represent a founder effect of Spanish origin.
Breast Neoplasms↗
Reticular perineurioma: a distinctive variant of soft tissue perineurioma.
Soft tissue perineurioma is a relatively recently characterized, uncommon tumor composed of perineurial cells exhibiting immunoreactivity for epithelial membrane antigen (EMA). These lesions occur preferentially in adults and may arise in a wide variety of anatomic sites. We report the clinicopathologic, immunohistochemical, and ultrastructural features of six cases of a poorly recognized morphologic variant of soft tissue perineurioma, characterized by a highly distinctive reticular growth pattern. Four of the patients were women, two were men (age range, 34-61 yrs; median, 43 yrs). Four of the cases arose in the subcutis of the upper extremity; three were located distally (thumb, finger, palm), whereas one was situated more proximally near the elbow region. One case each was located in the gingiva and subcutaneous tissue of the inguinal region, respectively. In those cases in which clinical information was available (n = 5), the lesions were asymptomatic and had been present from 4 months to 10 years before resection. Tumor size ranged from 1.5 cm to 10 cm (median size, 4.25 cm). Microscopically the lesions demonstrated a predominantly lace-like or reticular growth pattern composed of anastomosing cords of fusiform cells with bipolar cytoplasmic processes and palely eosinophilic cytoplasm. Nuclei were centrally placed, ovoid to fusiform in shape, and no mitoses were seen. Transition to more cellular areas was focally present in all cases. The stroma was variably collagenous to myxoid. Immunohistochemically all six cases stained positively for EMA but not for S-100 protein. Two cases demonstrated focal positive cytoplasmic staining for cytokeratin, whereas one case was focally desmin positive. Ultrastructural examination of two tumors showed typical features of perineurial cells. Follow up (available in only two cases) showed no evidence of recurrence. Reticular perineurioma of soft tissue represents an unusual morphologic variant within the perineurioma group, which should be distinguished from myoepithelial tumors, extraskeletal myxoid chondrosarcoma, and myxoid synovial sarcoma.
Adult↗
Auriculotemporal (Frey) syndrome in late childhood: an unusual variant presenting as gustatory flushing mimicking food allergy.
Auriculotemporal or Frey syndrome is characterized mainly by recurrent episodes of facial gustatory flushing and/or sweating, limited to the cutaneous distribution of the auriculotemporal nerve. Although relatively common in adults following injury to the auriculotemporal nerve or parotid disease, the condition has rarely been reported in children. Moreover, in childhood, auriculotemporal syndrome has been described mainly in infancy and early childhood as a sequel of perinatal birth trauma resulting from assisted forceps delivery. We report a 13-year-old girl with a 2-month history of recurrent, painless, preauricular gustatory flushing without sweating, initially suspected to be a food allergy. Detailed inquiry revealed a history of a bicycle accident with mandibular condyle fracture 7 years prior to the onset of symptoms. Our patient demonstrates an unusual presentation of auriculotemporal syndrome in late childhood as gustatory flushing mimicking food allergy. Awareness of this variant is essential for prompt recognition, thus avoiding unnecessary laboratory tests, especially as this condition usually resolves spontaneously.
Adolescent↗
Long-read sequencing of single cell-derived melanoma subclones reveals divergent and parallel genomic and epigenomic evolutionary trajectories.
Tumor evolution is driven by various mutational processes, ranging from single-nucleotide variants (SNVs) to large structural variants (SVs) to dynamic shifts in DNA methylation. Current short-read sequencing methods struggle to accurately capture the full spectrum of these genomic and epigenomic alterations due to inherent technical limitations. To overcome that, here we introduce an approach for long-read sequencing of single-cell derived subclones, and use it to profile 23 subclones of a mouse melanoma cell line, characterized with distinct growth phenotypes and treatment responses. We develop a computational framework for harmonization and joint analysis of different variant types in the evolutionary context. Uniquely, our framework enables detection of recurrent amplifications of putative driver genes, generated by independent SVs across different lineages, suggesting parallel evolution. In addition, our approach revealed gradual and lineage-specific methylation changes associated with aggressive clonal phenotypes. We also show our set of phylogeny-constrained variant calls along with openly released sequencing data can be a valuable resource for the development of new computational methods.
Journal Article↗
Dermatofibrosarcoma protuberans: A clinicopathologic analysis of patients treated and followed at a single institution.
BACKGROUND: Despite optimal surgical therapy for patients with dermatofibrosarcoma protuberans (DFSP), some patients still continue to develop local recurrence. The authors' objective was to identify and analyze clinicopathologic factors for disease free survival in a large group of patients who were followed prospectively at a single institution. METHODS: Prospectively collected data and pathology slides were available for review from 159 patients with primary or recurrent DFSP who underwent treatment between July 1950 and July 1998. The study group was comprised of patients with either the "classic" form of DFSP or the fibrosarcomatous "high grade" variant of DFSP (FS-DFSP). Patient, tumor, pathologic, and treatment factors were analyzed using the log rank test for univariate influence and Cox regression analysis for multivariate influence. Local recurrence free survival was determined by the Kaplan-Meier actuarial method. RESULTS: Of the 159 patients who comprised the current study group, 134 (84%) had the classic form of DFSP. The FS-DFSP variant was found in the remaining 25 patients (16%). The overall 5-year local recurrence free survival rate was 75%, with a median follow-up of 4. 75 years. The 5-year recurrence free survival rate for each group was 81% and 28%, respectively. On univariate analysis, age > 50 years, very close (< 1 mm) to positive microscopic margins, FS-DFSP variant, high mitotic rate, and increased cellularity were unfavorable prognostic factors. Multivariate analysis determined very close (< 1 mm) to positive microscopic margins and FS-DFSP variant to be independent adverse prognostic factors. For the 34 patients who developed a recurrence after surgical resection (21%), the median time to local recurrence was 32 months. Of the patients in this group, two died from metastatic disease. CONCLUSIONS: The prognosis after surgical resection with negative and sometimes positive microscopic margins for patients with DFSP is very good. However, increased age, high mitotic index, and increased cellularity are predictors of poor clinical outcome. The FS-DFSP variant represents a much more aggressive tumor with metastatic potential. Patients who are treated with curative intent for FS-DFSP should undergo aggressive attempts at complete surgical resection. Patients with recurrent classic DFSP without evidence of adverse prognostic features may benefit from conservative management, especially in the setting of potentially unresectable disease.
Adolescent↗
Primary Ki-1-positive anaplastic large-cell lymphoma: a distinct clinicopathologic entity.
The morphology of anaplastic large-cell lymphoma (ALCL) is associated with a clinical syndrome of peripheral lymphadenopathy (> 80%) and frequent extranodal disease (> 40%) in children and young adults (median age < 40 yrs.). Skin lesions occur in more than 20% of patients; other extranodal sites are bone, soft tissue, gastro-intestinal tract, lung, and pleura. Marrow involvement is infrequent (< 10%). Features that distinguish ALCL from Hodgkin's disease (HD) are noncontiguous nodal disease (> 50%), infrequent mediastinal mass (< 20%), and frequent inguinal lymphadenopathy (> 40%). Most patients present with stage III/IV disease. Stage is highly predictive of achieving complete remission, disease-free survival, and overall survival. Localized skin lesions have an excellent prognosis and occasional spontaneous regressions are noted. Distinctive histopathologic features of ALCL are partial lymph node involvement with sinus infiltration, sparing of B-cell regions, and tumor cell pleomorphism. Other features are high mitotic rate, necrosis, fibrosis, and plasma cell infiltrates. Morphologic variants of ALCL resemble carcinoma, syncytial variant of nodular sclerosing HD, true histiocytic lymphoma or interdigitating cell sarcoma, and mycosis fungoides. ALCL can be distinguished from these morphologically similar disorders by immunophenotype (CD30+, CD45+, CD15-, EMA+, BNH9+, keratin-, lysozyme-). A recurrent cytogenetic translocation, t(2;5) (p23; q35), has been observed among morphologic variants, including a small-cell-predominant variant and tumor cell line which contains a spectrum of small cerebriform and large anaplastic CD30+ cells. 70% of ALCL cases are of T-cell lineage, 15% B, 5% T/B, and 10% undefined.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
[Clinical value of CEA studies in patients with benign and malignant breast diseases with special reference to oncologic after care].
Carcinoembryonic antigen (CEA) was assayed by radio immunoassay in serum of 87 patients with breast cancer and 85 patients with benign breast tumors from 1983 to 1986. The sensitivity of 43%, the specificity of 89%, the predictive values in regard to a positive assay result of 75% and in regard to a negative assay result of 67% was determined in consideration of a changed prevalence. It is referred to the importance of the estimation of CEA in the individual diagnosis, monitoring and follow up of patients with breast cancer. It is claimed the follow up for the premature recording of a recurrency the aid of CEA-estimation in always the same technical variant at the same patient.
Breast Neoplasms↗
Locally recurrent endometrioid adenocarcinoma of the prostate after radical prostatectomy.
Endometrioid carcinoma of the prostate is considered a variant of classical prostatic ductal carcinoma. Endometrioid carcinoma variant often has the unique clinical presentation of gross hematuria. The propensity of this tumor to spread within the urothelium makes local failure of curative therapy commonplace. We present 2 representative cases with a review of followup surveillance procedures and treatment options for the local recurrence once identified.
Adenocarcinoma↗
[Surgical anatomy of the terminal portion of the small subcutaneous vein and methods of phlebectomy].
Based on a careful preparation of the small saphenous vein during 218 operations in patients with venous varicosity of the lower extremities, studies of the observed topographic variants of the terminal portion of the small saphenous vein, and observations over 48 patients with postoperative recurrent varices, it is concluded that the surgical anatomy of the terminal portion of the vein involved is characterized by a multitude of topographic variants, the knowledge of which facilitates the task of a surgeon in phlebectomy for varicosity and the postthrombophlebitic syndrome.
Adolescent↗
[A comparative clinico-morphological analysis of acute myelo- and myelomonoblastic leukemias in children and adults].
Previous morphocytochemical, immunological and cytogenetic analyses of blast cells in 174 children and 188 adults admitted to Cancer Research Center have shown that compared to adults in children leukemic precursors belong to earlier stage of differentiation similar to polypotent cell. The analysis covered 2 FAB-variants of ANLL comparable by the number of patients and intensity of the given chemotherapy (M2 and M4 ANLL FAB variants). The study included 65 children (50 with M2 and 15 with M4 FAB variants) and 43 adults (26 with M2 and 17 with M4 FAB variants) given therapy of standard intensity in the regimen 3+7 and 2+5. The children more frequently demonstrated involvement of the liver, spleen and peripheral lymph nodes. The percentage of complete remissions in both groups was not significantly different. 2- and 3-year recurrence-free survival was similar in two age groups with M2 FAB variants of ANLL. However, in M4 variant in adults this survival made up 18% against 0% in children. The differences may arise from lower peroxidase activity in children than in adults. It is suggested that M4 FAB variant in adults may indicate better prognosis than in children. Therefore, therapy in children with M4 FAB ANLL variant should be intensified.
Adolescent↗
A new X-linked variant of chronic granulomatous disease characterized by the existence of a normal clone of respiratory burst-competent phagocytic cells.
Chronic granulomatous disease (CGD) is characterized by recurrent infections, and is usually associated with a complete inability of phagocytic cells to generate superoxide anion (O2-). Rarely, variant forms of CGD have been reported in which there is reduced, but detectable, O2- production by phagocytic cells. We describe three adult males in two kindreds with a unique form of X-linked cytochrome b558-deficient (X91-) CGD not previously reported. All three patients had two distinct populations of phagocytic cells, with one subset capable of normal respiratory burst activity and the other larger subset inactive, as in classic CGD (X91 (0)). The respiratory burst activity in neutrophils purified from each patient was approximately 10% of normal as determined by O2- production, O2 consumption, cytochrome b558 spectroscopy, and membrane oxidase activity using a cell-free activation system. In contrast with other patients with X91(-)-variant CGD, the unique feature of these patients is the presence of a small but significant population (5% to 15%) of circulating neutrophils and monocytes with completely normal respiratory burst activity as assessed by nitroblue tetrazolium (NBT) reduction and flow-cytometric measurement of dihydrorhodamine oxidation. NBT reduction of peripheral blood granulocyte-macrophage progenitor cells also showed the presence of a subset of colonies derived from myeloid progenitor cells that had normal respiratory burst capabilities. A mosaic XX chromosome karyotype and an unstable oxidase complex that might occur during myeloid maturation were both excluded as possible explanations. In these families, the molecular defect in the gp91-phox gene, which is currently under investigation, appears to prevent expression of the gene in the majority of neutrophils, but not in a small subset. Our studies suggest that commitment to either a respiratory burst-competent or -incompetent phagocytic cell occurs at the level of the myeloid progenitor cell.
Adult↗
Petrified cardiac myxoma masquerading as organized atrial mural thrombus.
To our knowledge, petrified cardiac myxoma is a heretofore undescribed histologic variant of atrial myxomas. It is an obsolescent myxoma that has been converted to a sclerosiderotic nodule by impregnation of the tumor's stromal connective tissue fibers with iron, calcium, and ceroid pigments, presumably following recurrent hemorrhage in the myxoma over time. Four cases of this unusual histologic variant of cardiac myxoma were identified from among 22,150 autopsies performed over the 25-year period, 1954 through 1979. These four cases were asymptomatic incidental postmortem findings discovered in two men (54 and 82 years of age) and two women (66 and 80 years of age). The original autopsy diagnoses of the left atrial lesions were fibrosiderotic nodule (Gamna-Gandy body) in one patient and organized mural thrombi in the other three patients.
Aged↗
CD44 variant exon epitopes in primary breast cancer and length of survival.
CD44 designates a group of closely related cell-surface proteins generated by alternative splicing. We have previously shown that splice variants carrying sequences encoded by exon v6 are preferentially expressed in metastatic animal cancer cell lines and that they confer metastatic behaviour on non-metastatic animal tumour cell lines. In this study we set out to assess the expression of CD44 epitopes specific for variant exon sequences in human breast cancer and their potential for determining prognosis. We used affinity-purified polyclonal sera and four monoclonal antibodies raised against the human homologues of CD44 variant exon sequences to investigate the presence of CD44 on 100 primary invasive breast tumours, 12 local recurrences, 18 lymph node metastases, and normal tissue controls. Whereas normal mammary ductal epithelial cells and cells derived from hyperplastic lesions do not express CD44 variant exons, expression of v3, v5, and v6 epitopes was found in most tumour samples. The DIII (exon v6) epitope was present in 84% of the primary tumours and in 100% of axillary lymph node metastases and local recurrences. The presence of these CD44 epitopes is correlated with poor overall survival. 15 patients with exon-v6-negative tumours had good survival compared with 76 patients with exon-v6-positive tumours (p = 0.005; log rank test). Multivariate analysis showed that the CD44 epitope encoded by exon v6 was a good marker for prognosis independent of progesterone receptor, lymph node status, tumour size, and grade.
Adult↗
Correlation of CD44S expression in renal clear cell carcinomas with subsequent tumor progression or recurrence.
BACKGROUND: Recent reports have shown altered expression of CD44 in renal cell carcinomas. However, to the authors' knowledge there are no data correlating CD44 expression in renal cell carcinomas with subsequent tumor progression or recurrence, nor is there information about the presence of particular splice variants of CD44 in these tumors. METHODS: The authors examined the immunohistochemical expression of CD44S, the standard isoform of CD44, in renal cell carcinomas from 43 patients using 2 different monoclonal antibodies, Mab2137 and Hermes-3. In addition, they stained the renal cell carcinomas with antibodies to 2 splice variants of CD44, CD44v3 and CD44v6. RESULTS: Increased staining of renal clear cell carcinomas with Mab2137 was observed in high grade versus low grade tumors (45% vs. 0%, P = 0.013), whereas increased staining of clear cell carcinomas with Hermes-3 was noted in high stage versus low stage tumors (40% vs. 0%, P = 0.006). Few tumors stained with antibodies to CD44v3. Although increased expression of the splice variant CD44v6 was noted in papillary versus clear cell carcinomas, and increased staining of papillary carcinomas with Mab2137 and with antibodies to CD44v6 was noted for low stage versus high stage tumors, these differences did not achieve statistical significance. Clinical follow-up of at least 43 months was available for 26 patients. Six of these patients (five with clear cell carcinoma and one with papillary carcinoma) developed progressive or recurrent disease. The primary tumors from all 5 patients with progressive or recurrent clear cell carcinoma showed staining with Mab2137, whereas the primary tumors from only 2 of the 15 patients with at least 43 months follow-up and no evidence of progressive or recurrent clear cell carcinoma (13%) showed staining with Mab2137 (P = 0.001). Alternatively, 5 of 7 clear cell carcinomas (71%) that stained with Mab2137 were from patients who subsequently developed recurrence or progression, compared with 0 of 13 clear cell carcinomas that did not stain. Similar findings were not observed for papillary carcinomas, which appeared to be biologically distinct from clear cell carcinomas. CONCLUSIONS: CD44S staining with Mab2137 correlates with progression or recurrence of clear cell renal cell carcinoma. CD44S may, therefore, play a pathogenetic role in tumor progression.
Adult↗