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PubMed2004

Recurrent aneurysmal fibrous histiocytoma.

Aneurysmal fibrous histiocytoma is a rare variant of cutaneous fibrous histiocytoma that results from blood vessel proliferation and haemorrhage into a fibrous histiocytoma. The resulting lesion has a very different clinical appearance, hence the potential confusion with other skin lesions. This report describes the case of a 48 year old woman with a recurrent fibrous histiocytoma with prominent vasculature, which over a three year period recurred on two occasions, showing more progressive features of the aneurysmal variant. In addition, squamous lined cysts were present within this tumour, a finding that has not been described previously. The histological features of this rare lesion and the importance of the differential diagnosis from other similar appearing malignant lesions will be discussed.

Cysts↗

PubMed1996

Tubular carcinoma of the breast. Predicting axillary nodal metastases and recurrence.

BACKGROUND: Tubular carcinoma of the breast, a well-differentiated variant of infiltrating ductal carcinoma, has been regarded as a very favorable histologic subtype. The infrequency of nodal metastases and low recurrence rates have led to questions about the value of axillary dissection. OBJECTIVE: The authors evaluated the frequency of axillary nodal metastases, the prognostic value of histologic features of the primary tumor, and treatment outcome in patients with tubular carcinoma of the breast. METHODS: This retrospective analysis evaluated 50 patients who received diagnoses of tubular carcinoma from The University of Texas M. D. Anderson Cancer Center between 1944 and 1992. Medical records were reviewed for information about the patient, the tumor, treatment, and outcome. Hematoxylin-eosin stained sections were reviewed to confirm the diagnosis and assess histologic features. RESULTS: The median tumor diameter was 1.0 cm. Nine (20%) of 44 axilla had histologically confirmed lymph node involvement. Lymph node involvement was neither infrequent nor predicted by features of the primary tumor. Recurrences developed in 4 patients, and 1 patient died of tubular carcinoma. The 5-year disease-free survival rate was 88%. The local therapy used, mastectomy or breast preservation, did not affect disease-free survival. Contralateral cancer was noted in 26% of the patients. CONCLUSIONS: Axillary metastases occur in 20% of patients and are not predicted by features of the primary tumor. Breast preservation is a safe treatment option for tubular carcinoma of the breast.

Adenocarcinoma↗

PubMed1988

Liver transplantation for malignant disease. Results in 93 consecutive patients.

Ninety-three patients with malignant disease underwent orthotopic liver transplantation between May 1968 and April 1987 in the Cambridge/King's College Hospital program. Of 50 patients with primary hepatocellular carcinoma (HCC) (19 with cirrhosis, 31 without cirrhosis, including 7 with fibrolamellar variant), 37 (74%) survived for more than 3 months, and in this group evidence of tumor recurrence was obtained in 24 (64.9%), the longest survivor being 11.8 years post-transplant, and three survived for more than 5 years. Although there is no correlation between the frequency of tumor recurrence and underlying cirrhosis, or histologic type (except fibrolamellar variant), it was observed earlier in those with moderate/poorly differentiated tumors and also when prednisolone and azathioprine was used for immunosuppression. Tumor recurred in all but two of those with peripheral or central cholangiocarcinoma (one alive at 6.1 years) with median survival times of 34 weeks and 56 weeks for the central and peripheral types, respectively. Among the unusual primary tumors, one with epithelioid haemangioendothelioma developed tumor recurrence at 2 years, one of two patients with apudoma is tumor-free at 2.2 years, and the one patient with bile-duct papillary cystadenocarcinoma is alive at 1.7 years. For the secondary hepatic malignancy group, survival times were shorter with little palliation except for two patients with carcinoid syndrome who were free of associated symptoms at 6 and 10 months. Despite the overall high frequency of tumor recurrence in most categories of hepatic malignancy, liver transplantation gave worthwhile survival with a number of patients cured and in the others considerable palliation of symptoms.

Adenoma, Bile Duct↗

PubMed1989

Perivascular nerve lesion of the coronary artery involved in spasm in a patient with variant angina.

An autopsy case of a 52-year-old man with typical variant angina is reported. He had recurrent attacks of chest pain at rest, particularly from midnight to early morning, associated with ST segment elevation in the electrocardiogram. At autopsy, degenerative changes and fibrosis were confirmed light microscopically in the perivascular nerves of the coronary artery involved in spasm. This finding indicates an intimate relationship between coronary spasm and the autonomic nervous system.

Angina Pectoris, Variant↗

PubMed2002

Recurrent Miller fisher syndrome: a case report.

Miller fisher syndrome (MFS) is a variant of Guillain-Barre syndrome characterized by the triad of ophthalmoplegia, ataxia and areflexia. Recurrences are exceptional with MFS. A case with two episodes of MFS within four years is reported. He presented with findings of ophthalmoplegia, ataxia, areflexia, and oropharyngeal weakness and mild distal sensory impairment during both episodes. Electrophysiological findings showed reduced compound muscle action potentials and sensory nerve action potentials with no evidence of conduction blocks. Nerve biopsy showed segmental demyelination. MRI of brain was normal. He responded well to immunoglobulins during both episodes suggesting that immunomodulating drugs have a role in the treatment of MFS.

Adult↗

PubMed2004

Fibrosing cholestatic hepatitis secondary to precore/core promoter hepatitis B variant with lamivudine resistance: successful retransplantation with combination adefovir dipivoxil and hepatitis B immunoglobulin.

Fibrosing cholestatic hepatitis (FCH) is a peculiar variant of hepatitis B virus (HBV) infection in immunocompromised patients characterized by rapid viral replication. Posttransplant patients receiving lamivudine for prophylaxis or treatment of HBV infection may develop drug resistance due to viral mutants, but FCH is rare because escape mutants are usually replication deficient. We report the development of FCH due to lamivudine-resistant HBV mutants in 2 patients at 12 and 13 months after liver transplantation. Rapidly progressive graft failure, accompanied by an escalating HBV DNA level, developed within weeks of onset. Analysis of gene sequence variation by polymerase chain reaction (PCR) and direct sequencing showed that both had a core promoter variant A1762T/G1764A and 1 had a concomitant precore stop codon G1896A variant in prelamivudine and postrecurrence serum samples. Comparison of the HBV polymerase gene in the 2 serum samples revealed a single mutation with methionine-to-isoleucine substitution at codon 552 (M552I) in both patients. "Add-in" treatment with adefovir dipivoxil resulted in a more than 2 to 3log10 reduction in HBV DNA level within 2 weeks and retransplantation was performed with adefovir dipivoxil and hepatitis B immunoglobulin (HBIG) prophylaxis. Both patients were alive at 15 months and 48 months after retransplantation, with normal graft function and serum negative for HBsAg and HBV DNA by quantitative PCR (< 200 copies/mL). The current report demonstrates that recurrent graft infection by precore/core promoter variant with lamivudine-resistant escape mutation may result in FCH. With combination of adefovir and high-dose HBIG, however, long-term survival can be achieved after retransplantation.

Adenine↗

PubMed1997

Recurrent Hodgkin's disease after bone marrow transplantation.

Histologic features of recurrent Hodgkin's disease (HD) after conventional therapy are well known, but few studies describe HD after bone marrow transplantation (BMT). Histologic material from 63 patients who underwent BMT performed to treat recurrent nodular sclerosing HD (NSHD) between 1985 and 1994 was examined; 13 of the 63 patients had histologically proved recurrent disease after BMT. Histologic material and clinical findings from the original diagnostic biopsy specimen and pre-BMT and post-BMT specimens were available from our study population of eight patients (five male, three female; age range, 16 to 38 years; median age, 27.5 years). Seven patients had recurrent NSHD after BMT; sites of recurrence included lymph nodes only (four patients), and lymph nodes and lung, lung and liver, and lung only (one patient each). In one patient, a high-grade non-Hodgkin's B-cell lymphoma developed in the large intestine 5 years after BMT. In another, disease progressed from grade 1 in the original biopsy specimen to grade 2 in both the pre-BMT and post-BMT recurrent HD biopsy specimens. Post-BMT biopsy specimens of recurrent HD with lung involvement revealed a substantial increase in sclerosis and fibroblastic features. Paraffin immunoperoxidase studies in seven patients demonstrated substantial change in phenotype of Reed-Stemberg cell variants in only one post-BMT recurrent HD specimen, which showed a +2 reaction with CD30 (Ki-1). No substantial differences in the reactive component were noted between the original biopsy specimen and pre-BMT and post-BMT specimens of recurrent disease. In summary, histologic findings of post-BMT recurrent NSHD do not differ significantly from those of the original diagnostic biopsy or pre-BMT recurrent HD specimens. The lung is the most common site of extranodal post-BMT recurrence. In one patient, high-grade non-Hodgkin's B-cell lymphoma developed after BMT performed to treat recurrent HD.

Adolescent↗

PubMed2002

Desmoplastic variant of ameloblastoma: report of two cases and review of the literature.

BACKGROUND: The desmoplastic ameloblastoma exhibits important differences in anatomical distribution, histologic appearance and radiographic findings compared with the classic type of ameloblastoma. The purpose of this article is to assist the dental community in better understanding this variation in odontogenic tumor. CASE DESCRIPTIONS: The authors present two cases of desmoplastic variant of ameloblastoma localized in the anterior portion of the jaw. The tumors were expansile, destructive and painless. The radiographic findings showed diffuse, mixed (radiopaque/radiolucent) lesions with cortical bone destruction. Block excision was performed in both cases. Follow-up examination one and two years later disclosed no recurrence of tumor. CLINICAL IMPLICATIONS: The desmoplastic variant of ameloblastoma tends to infiltrate between bone trabeculae. Curettage leaves islands of tumor within bone, which later manifest as recurrences. Therefore, block excision is the most widely used treatment to avoid recurrence.

Ameloblastoma↗

PubMed2026

Exploring the Melanoma and Pancreatic Cancer Phenotype of a Potential CDKN2A Founder Variant, I49T (c.146T>C; p.Ile49Thr), in Individuals of Predominantly Mexican Ancestry.

PURPOSE: Pathogenic/likely pathogenic variants (P/LPVs) in the CDKN2A gene cause an increased risk of melanoma (MEL) and pancreatic cancer (PANC). The CDKN2A variant I49T (c.146T>C), reported to be recurrent in Hispanics, has conflicting pathogenicity classifications at laboratories, affecting clinical care. Multiple genetics clinics collaborated to explore cancers associated with I49T. METHODS: Institutional clinical databases were queried for the CDKN2A variants, I49T, known P/LPVs, and c.-2G>A (a benign variant [BV]), and history of PANC and MEL was abstracted. A combination of statistical tests was used to investigate cancer history associations. RESULTS: Data on 203 individuals, with qualifying CDKN2A variants detected on multigene testing between 2012 and 2023, were analyzed (I49T, n = 101; known CDKN2A P/LPVs, n = 57; BV, n = 45). Those with I49T were 91% less likely to have MEL than known CDKN2A P/LPVs (odd ratio [OR] = 0.089 [95% CI, 0.031 to 0.025]; P < .001) and were also less likely to have PANC (OR = 0.45 [95% CI, 0.14 to 1.41]; P = .17). However, mean age at PANC diagnosis for I49T was 56.0 years, significantly younger than known CDKN2A P/LPVs (μ = 71.0 years; P = .026). CONCLUSION: In the largest I49T study to date to our knowledge, MEL was significantly less frequent compared with known CDKN2A P/LPVs. Although a nonsignificant trend was observed for less PANC in I49T than known P/LPVs, individuals with I49T presented with PANC at a significantly younger age than those with known CDKN2A P/LPVs. The presence of I49T in Hispanics of mostly Mexican ancestry supports that it is a founder variant, relevant to understanding cancer risk in a large proportion of Hispanics in the United States.

Humans↗

PubMed2006

Influence of genetic variation in the C-reactive protein gene on the inflammatory response during and after acute coronary ischemia.

The aim of this research was to assess whether common genetic variants within the C-reactive protein gene (CRP) are related to the degree of acute rise in plasma C-reactive protein (CRP) levels following an acute coronary syndrome (ACS). While polymorphisms within CRP are associated with basal CRP levels in healthy men and women, less is known about the relationship of such genetic variants and the degree of CRP rise during and after acute ischemia. Plasma CRP is associated with increased rates of recurrent coronary events. We evaluated seven common genetic variants within CRP and assessed their relationship to the degree of rise in CRP levels immediately following an acute coronary syndrome in 1827 European American patients. Variants in the putative promoter region, -757T > C and -286C > T > A, were associated with the highest CRP elevations after ACS. Patients with two copies of the A allele of SNP -286C > T > A had median CRP values of 76.6 mg/L, compared to 11.1 mg/L in patients with no copies of the rare variant (p-value <0.0001), post ACS. The lowest CRP values were found for patients with minor alleles of the exonic 1059G > C and the 3'untranslated region 1846G > A SNPs. For example, patients homozygous for the minor allele of 1059G > C had 71% lower median CRP values than those homozygous for the major allele [3.5 vs 12.0 mg/L, p < 0.0001]. These trends persisted in the chronic stable phase after ischemia had resolved, and after adjustment for infarct size by peak creatinine kinase levels and clinical status by Killip class. Assessment of CRP genetic variants identified patients with higher and lower CRP elevation after acute coronary syndrome.

Acute Disease↗

PubMed2001

Lipoastrocytoma: a rare low-grade astrocytoma variant of pediatric age.

We report on two children with cerebral gliomas showing extensive lipomatous change of tumor cells. One tumor was a large mass occupying the temporal and occipital lobes of the left hemisphere; the other was a cystic lesion with a mural nodule in the left frontal lobe. Histologically, both tumors were composed of glial cells that contained fat droplets coalescing into a single large droplet, thus resulting in an appearance similar to adipocytes. Immunohistochemistry showed GFAP positivity of tumor cells, which was maintained in the cytoplasmic rim of lipidized cells. Synaptophysin and neurofilaments were negative. Ki-67/Mib1 labeling index was low. Electron microscopy showed intracytoplasmic lipid vacuoles, abundant intermediate filaments and a basal lamina surrounding the cell bodies. Molecular genetic analysis of one tumor revealed no TP53 mutation (exons 4-10), no loss of CDKN2A, and no amplification of EGFR, CDK4 or MDM2. Both patients are alive and well after 3 and 7 years, respectively. However, one of them had to be re-operated on circumscribed local recurrences. Our cases represent a rare variant of low-grade astrocytoma that may be designated as "lipoastrocytoma".

Age Factors↗

PubMed2000

Metabolic gene polymorphisms and risk of dysmenorrhea.

We conducted a molecular epidemiologic study in rural China to investigate the association of the cytochrome P450 2D6 (CYP2D6) and glutathione S-transferase Mu (GSTM1) polymorphisms with dysmenorrhea. This report includes 435 subjects, 129 with and 306 without any history of dysmenorrhea, who did not smoke or drink alcohol. We obtained information on dysmenorrhea and major covariates by questionnaire interview. We used categorical methods and logistic regression models to evaluate the individual and combined associations of CYP2D6 and GSTM1 polymorphisms with dysmenorrhea and its subgroups, occasional (N = 70) and recurrent (N = 59), with adjustment for age, education, occupation, passive smoke exposure, age of menarche, parity, contraceptive method, height, and body mass index. Both variant CYP2D6 and GSTM1 genotypes were associated with increased risk of recurrent dysmenorrhea [for CYP2D6, odds ratio (OR) = 1.7 and 95% confidence interval (95% CI) = 0.9-3.1; for GSTM1, OR = 1.8 and 95% CI = 1.0-3.4). There was no appreciable association between these variant genotypes and occasional dysmenorrhea. When both the CYP2D6 and GSTM1 genotypes were considered together, the highest risk of recurrent dysmenorrhea was found among women with variant genotypes in both CYP2D6 and GSTM1 (OR = 3.1; 95% CI = 1.2-8.0). This study provides evidence of genetic susceptibility to recurrent dysmenorrhea.

Adult↗

PubMed1979

[Frequency of chromosome variants in human populations].

Chromosome variants were analyzed in the course of the population chromosome investigation of 6000 newborns and clinical cytogenetic studies of 403 married couples with recurrent spontaneous abortions, stillbirths or offsprings having congenital malformations or Down's syndrome. The following variants were determined: 1) Igh+, 9gh+, 16gh+ - the enlargement of the secondary constrictions of the size, more than 1/4 of the long arm of the chromosome; 2) Dp+ or Gp+ - the enlargement of the short arms of acrocentrics, their size being more than the short arm of the chromosome 18; 3) Ds+ or Gs - large satellites of the acrocentrics which are equal or more than the thickness of the chromatids of the long arms; 4) Es+ - satellites on the short arms of the chromosomes 17 or 18; 5) Dss of Gss - double satellites; 6) Yq+ - the enlargement of the long arm of Y chromosome, the size of which being more than G chromosome; 7) Yq- - deletion of the long arm of Y chromosome, the size of the long arm being less than chromosomes 21--22. The total frequency of variants in newborns was 12.8/1000 births. The incidence of different types of variants per 1000 births was as follows: Igh+ - 0.33; 9gh+ - 0.17; 16gh+ - 0.50; Ds+ - 2.33; Dp+ - 1.50; Dp- - 0.17; Gs+ - 0.83; Gp+ - 2.17; Yq+ - 6.91/1000 males; Yg- - 0.99/1000 males; double variants - 0.33; other variants - 0.33. 4.0% of married couples with recurrent spontaneous abortions had major chromosome aberrations, 14.6% - extreme variants of chromosomes. Among 113 couples with the history of congenital malformations in their offsprings major chromosome abnormalities were found in 4.4%, chromosome variants - 13.3%. The frequency of chromosome variants among 139 patients with Down's syndrome was 7.2%. In one case Robertsonian translocation t(DqGa) was determined. The most frequent types of variant chromosomes were Ds+, Dp+, Es+, Yq+.

Abortion, Habitual↗

PubMed2003

Influence of CLOCK gene polymorphism on circadian mood fluctuation and illness recurrence in bipolar depression.

Recent studies showed that a polymorphism (T to C nucleotide substitution) in the 3' flanking region of the human CLOCK gene is associated with diurnal preferences of human healthy subjects, with higher "eveningness" in subjects carrying at least one copy of the C allele. We investigated the possible role of CLOCK gene polymorphism in the regulation of diurnal mood fluctuations during a major depressive episode. Sample (n = 101) was collected, in the context of previously reported trials, among patients affected by bipolar disorder type I, depressive episode without psychotic features, free of psychotropic medications. Perceived mood levels were assessed three times a day with self-administered visual analogue scales. Genotype groups showed no significant difference in diurnal mood fluctuations. When stratifying the sample by including only patients with an adequate period of observation (duration of illness higher than 5 years, n = 69), we post-hoc observed a significantly higher recurrence rate in homozygotes for the C variant, which was almost double than that of the other genotype groups. This preliminary observation leads to hypothesize a role for the CLOCK gene polymorphism in the regulation of long-term illness recurrence in bipolar disorder. Given the post-hoc nature of the finding, replication in independent samples is necessary to confirm it.

Bipolar Disorder↗

PubMed1979

Heterochromatic polymorphism in spontaneous abortions.

Since the advent of C-banding as a routine diagnostic procedure, the significance of heterochromatic polymorphism has been questioned. Some workers have considered variations in heterochromatin in chromosomes 1 and 9 to be associated with fetal wastage, recurrent abortions, and abnormal phenotypes. Over a 15-month period, this laboratory made a study of the diagnostic significance of heterochromatic variants in 50 couples with a history of recurrent abortions. A control group of 50 couples with at least two normal children and no miscarriages was investigated simultaneously. The results indicated no significant difference in the heterochromatic regions between aborting and non-aborting couples.

Abortion, Habitual↗

PubMed2006

Idiopathic inflammatory demyelinating disorders after acute transverse myelitis.

Acute transverse myelitis (ATM) is commonly para-infectious. Recurrent ATM occurs in connective tissue diseases (CTD), infective myelitis and idiopathic inflammatory demyelinating disorders (IIDD) including multiple sclerosis (MS) and neuromyelitis optica (NMO). Previous studies might include NMO and idiopathic recurrent transverse myelitis (IRTM) as MS. The aim was to study the outcome of patients after a first attack of idiopathic ATM. Idiopathic ATM patients over a 6-year period were retrospectively studied. Known causes of myelopathy were excluded. Among 32 patients studied, 20 (63%) had single ATM attack upon follow up for 39-93 months, three developed recurrent ATM related to CTD (two systemic lupus erythematosus and one anti-Ro antibody positive) and nine (28.1%) developed recurrent neuroinflammation compatible with IIDD. Among IIDD patients, three had NMO, two restricted variant of NMO, three IRTM and one classical MS. NMO, its variant and IRTM had mean spinal MRI abnormality of 3.7, 2.1 and 3.9 vertebral segments respectively while non-recurrent ATM had 1.6 vertebral segments. Four (80%) of the five patients with NMO or its variant had poor neurological prognosis versus only one (5%) of non-recurrent ATM patients. IRTM patients had advanced mean onset age, 62 years vs. 43 years for non-recurrent ATM patients. In IIDD patients presenting with ATM as first attack of neuroinflammation, NMO and its variant (56%) were most frequent, then IRTM (33%), with classical MS (11%) the rarest. As long-term treatments for NMO are different from MS, early recognition of NMO and its variant is important for prevention of serious neurological deficits.

Adult↗

PubMed2026

Mutational signature stratification of recurrent gliomas reveals distinct patterns of genomic traits.

BACKGROUND: Although temozolomide (TMZ) is widely used for glioma treatment, its therapeutic benefit is limited by acquired resistance and recurrence, facilitated by intratumor heterogeneity. Mutational signatures (MSs) inform tumor evolution and reveal alterations associated with treatment response. METHODS: We performed molecular analyses of 96 glioma recurrences with sufficient private single-nucleotide variants relative to their matched primary tumors, stratified by their dominant MS. RESULTS: Four groups were identified: MS11/TMZ-related (n = 38), MS1/5/aging-related (n = 32), MS6/15/21/26/microsatellite instability (MSI)-related (n = 13), and other MS-related recurrences (n = 13). MS11/TMZ-related recurrences showed higher acquired mutational counts than the other groups (1338 vs 59 (MS1/5/aging) vs 57 (MS6/15/21/26/MSI) vs 57 (other MSs); P < .01). Mutations in SYNE2, SZT2, and FBN3 were restricted to recurrences with dominant or second-dominant MS11/TMZ-related signature (n = 41), and 85% (35/41) harbored mutations in these genes. In MS11/TMZ-related recurrences with RNA sequencing data (n = 17), mRNA co-expression analyses identified SYNE2-ATAD5 and SZT2-MAPKBP1 associations. Among MS11/TMZ-related recurrences, MS23 was frequent (44%, 18/41) and associated with higher acquired mutational counts (2089 vs 1188; P = .018) and more IDH-wildtype tumors (67% vs 30%; P = .037). MAPKBP1 mutations were enriched in MS23-positive recurrences (56% (10/18) vs 0% (0/23); P < .001). MS1/5/aging-related recurrences showed more frequent acquired chromosome 16q losses (22% vs 8% (TMZ) vs 0% (MSI) vs 0% (other); P < .05), which were associated with an increased fraction of genome altered relative to 16q-diploid cases (15% vs 7%; P = .01). CONCLUSIONS: These findings show that MS-based stratification of recurrences refines molecular characterization after therapy and nominates candidate biomarkers and pathways for functional studies of treatment-associated glioma evolution.

mutational signatures↗

PubMed1998

Minimally invasive management for first and recurrent pneumothorax.

Minimally invasive techniques for treatment of pneumothorax should yield the standard of results set with open procedures: the operative morbidity should remain less than 15%, and the recurrence rate less than 1%. In the era before video-assisted thoracic surgery, two minimally invasive variants were used. Chemical pleurodesis resulted in an unsatisfactory recurrence rate of at least 15%. In contrast, pleurectomy and apical stapling performed through a transaxillary minithoracotomy compared favorably with larger thoracotomy approaches, and allowed a reduced hospital stay. Evaluation of video-assisted thoracic surgical operations for spontaneous pneumothorax is hampered by a lack of controlled studies. The general impression is that morbidity did not decline significantly; the main determinant of complications is the patient's underlying health status. However, published recurrence rates range from 5% to 10%, in spite of a shorter follow-up time span. Optimized results are achieved when classic principles combining apical wedge resection and pleurodesis are applied. Reduction of hospital stay is not only a result of the new technology, but also changing drainage and discharge policies. Reduction of cost is debatable, because many studies do not consider the cost of video equipment. The main advantage when compared with open thoracotomy is reduction of postoperative pain. The only two available controlled studies conclude that there is no obvious advantage of video-assisted thoracic surgery when compared with conventional limited-access surgery. The future role of video-assisted thoracic surgery in this disease remains to be determined by a large-scale prospective evaluation.

Costs and Cost Analysis↗