Search PubMed⌕ Search

Biomedical subjects

E Calonje

Publications and source records attributed to E Calonje.

At least 37 records · Page 2Linked to original sources
PubMed2003

Genetic and functional analyses of FH mutations in multiple cutaneous and uterine leiomyomatosis, hereditary leiomyomatosis and renal cancer, and fumarate hydratase deficiency.

Germline mutations of the fumarate hydratase (FH, fumarase) gene are found in the recessive FH deficiency syndrome and in dominantly inherited susceptibility to multiple cutaneous and uterine leiomyomatosis (MCUL). We have previously reported a number of germline FH mutations from MCUL patients. In this study, we report additional FH mutations in MCUL and FH deficiency patients. Mutations can readily be found in about 75% of MCUL cases and most cases of FH deficiency. Some of the more common FH mutations are probably derived from founding individuals. Protein-truncating FH mutations are functionally null alleles. Disease-associated missense FH changes map to highly conserved residues, mostly in or around the enzyme's active site or activation site; we predict that these mutations severely compromise enzyme function. The mutation spectra in FH deficiency and MCUL are similar, although in the latter mutations tend to occur earlier in the gene and, perhaps, are more likely to result in a truncated or absent protein. We have found that not all mutation-carrier parents of FH deficiency children have a strong predisposition to leiomyomata. We have confirmed that renal carcinoma is sometimes part of MCUL, as part of the variant hereditary leiomyomatosis and renal cancer (HLRCC) syndrome, and have shown that these cancers may have either type II papillary or collecting duct morphology. We have found no association between the type or site of FH mutation and any aspect of the MCUL phenotype. Biochemical assay for reduced FH functional activity in the germline of MCUL patients can indicate carriers of FH mutations with high sensitivity and specificity, and can detect reduced FH activity in some patients without detectable FH mutations. We conclude that MCUL is probably a genetically homogeneous tumour predisposition syndrome, primarily resulting from absent or severely reduced fumarase activity, with currently unknown functional consequences for the smooth muscle or kidney cell.

Amino Acid Metabolism, Inborn Errors↗
PubMed2003

Blastic natural killer cell and extranodal natural killer cell-like T-cell lymphoma presenting in the skin: report of six cases from the UK.

BACKGROUND: Some lymphomas express natural killer (NK)-cell markers such as the neural cell adhesion molecule, which is recognized by the CD56 antibody. These lymphomas may present in the skin, but do not represent a homogeneous group. The new World Health Organization classification of lymphoma/leukaemia recognizes several types of NK/T-cell neoplasm, including blastic NK-cell lymphoma, which characteristically presents with cutaneous lesions. OBJECTIVES: To describe the clinical, pathological and molecular features in six cases of CD56+ lymphoma with cutaneous presentation. METHODS: The clinical, histopathological and immunophenotypic features of six patients were reviewed. In addition, in situ hybridization (ISH) to identify Epstein-Barr virus (EBV) mRNA, and polymerase chain reaction analysis to identify the presence of a clonal population of T cells or B cells were performed on lesional skin. RESULTS: All patients presented with widespread nodules and plaques, which in five cases were a characteristic purple colour. Four patients developed disseminated disease, three with neurological involvement. These four patients died between 14 and 46 months following diagnosis (median 30 months). In four of six cases the histopathological and immunohistological features were in keeping with a blastic NK-cell lymphoma. No clonal immunoglobulin heavy chain (IgH) or T-cell receptor (TCR) gene rearrangement was detected in the four cases consistent with an origin from NK cells. A further case fitted the criteria for an extranodal NK/T-cell lymphoma of nasal type and was also the only case to show evidence of EBV mRNA by ISH. A clonal T-cell population was identified in the final case. This patient also exhibited molecular evidence of a clonal B-cell population and a t(14;18) translocation confirmed by sequence analysis. CONCLUSIONS: Our data confirm that NK-cell lymphomas presenting in the skin are a heterogeneous group, and that in the U.K., blastic NK-cell lymphoma is more common than extranodal NK/T-cell lymphoma of nasal type. These lymphomas pursue an aggressive course, with rapid development of disseminated disease, and resistance to chemotherapy. Detailed immunophenotyping is needed to distinguish the different types. Our molecular data indicate that blastic NK-cell lymphoma cases lack clonal TCR/IgH gene rearrangements consistent with an NK-cell origin. Our ISH findings indicate that EBV plays a pathogenetic role only in extranodal NK/T-cell lymphoma of nasal type.

Adult↗
PubMed2003

Treatment of Darier's disease with photodynamic therapy.

BACKGROUND: Photodynamic therapy (PDT) using topical 5-aminolaevulinic acid (5-ALA) as a photosensitizer has been reported in the treatment of both neoplastic and benign cutaneous disorders. OBJECTIVES: To evaluate the efficacy of photodynamic therapy in selected patients with Darier's disease (keratosis follicularis). METHODS: Six patients with Darier's disease were assessed before and after treatment with PDT using 5-ALA and mean fluence rates of 110-150 mW cm-2. RESULTS: Of the six patients, one was unable to tolerate the treatment. Of the remaining five, all experienced an initial inflammatory response that lasted two to three weeks. In four of the five patients, this was followed by sustained clearance or improvement over a followup period of six months to three years. Three of these four patients were on systemic retinoids and the fourth had discontinued acitretin prior to PDT. In the fifth patient partial improvement was followed by recurrence after etretinate therapy was discontinued. Biopsy specimens taken immediately after the procedure in two patients demonstrated a mild inflammatory cell infiltrate in the dermis. A biopsy obtained eighteen months after PDT from a successfully treated area showed no signs of Darier's disease and a subtle increase of collagen in the upper dermis. CONCLUSIONS: Photodynamic therapy can be viewed as a potential adjunctive modality for Darier's disease but should not be considered as a substitute for retinoids in patients who require systemic treatment.

Adult↗
PubMed2003

Lymphomatoid contact dermatitis to para-tertyl-butyl phenol resin.

Lymphomatoid contact dermatitis refers to the relatively little known phenomenon of allergic contact dermatitis producing histological features suggestive of cutaneous T-cell lymphoma. We report the first case of lymphomatoid contact dermatitis in response to para-tertyl-butyl phenol resin.

Aged↗
PubMed2003

Cutaneous Waldenström's macroglobulinaemia.

We report a case of Waldenström's macroglobulinaemia that presented with infiltrated skin nodules and plaques but without systemic symptoms. Cutaneous manifestations such as purpura, oedema, urticaria and ulceration may be seen in Waldenström's macroglobulinaemia and are a consequence of hyperviscosity, cryoglobulinaemia and/or tissue deposition of immunoglobulins. Direct cutaneous infiltration by neoplastic lymphoid cells is less common, and very rare as the initial presentation of Waldenström's macroglobulinaemia.

Aged↗
PubMed2003

Deep penetrating naevus: clinicopathological study of 31 cases with further delineation of histological features allowing distinction from other pigmented benign melanocytic lesions and melanoma.

AIMS: To examine a series of deep penetrating naevus (DPN) and discuss the differential diagnosis of pigmented, deep penetrating melanocytic lesions and their biological potential. DPN has been described as a variant of common acquired intradermal melanocytic naevus. DPN remains poorly recognized by pathologists, partly attributable to its relatively rare occurrence. METHODS AND RESULTS: Thirty-one cases of deeply pigmented lesions were studied. The patients included 17 females and 14 males with an age range between 3 and 56 years (mean 25.8, median 23). The common clinical sites were face (n = 10) back (n = 6) and lower extremity (n = 7). The clinical diagnoses included various benign melanocytic naevi, and malignant melanoma, as well as non-melanocytic lesions. Histologically, all cases presented as wedge-shaped lesions composed of fusiform cells but also epithelioid melanocytes, with pale cytoplasm and oval nuclei. Pigment was identified in melanophages but also within lesional melanocytic cells. Nine cases contained mitotic figures. Nine cases showed the coexistence of 'ordinary' common acquired naevocytes, and seven lesions showed overlapping features with either ordinary blue naevus or Spitz naevus. In 13 lesions there was at least one feature that may cause concern as to the biological nature of the tumour. These include asymmetry, cytological atypia, inflammation, or an 'expansile' advancing margin. Each tumour was treated by simple excision; one lesion recurred after 1 year. No tumour metastasized. CONCLUSIONS: DPN is a distinct variant of melanocytic naevus. In some cases the histological features overlap with other benign melanocytic lesions. Criteria for recognizing malignant examples remain unclear, but cytological atypia and low mitotic activity do not necessarily portend a sinister outcome.

Adolescent↗
PubMed2002

Local and systemic expression of basic fibroblast growth factor in a patient with familial glomangioma.

Glomangiomas are rare cutaneous tumours composed of glomus cells, which are modified smooth muscle cells. The aetiology of this condition is thought to involve a mutation in a novel gene acting to regulate angiogenesis. We report a patient from a large family with three generations affected by familial multiple glomangiomas. We hypothesized that the growth factors basic fibroblast growth factor and vascular endothelial growth factor, which stimulate/regulate angiogenesis could be involved in the pathogenesis of these lesions. Therefore, using enzyme-linked immunosorbent assays and immunohistochemistry, respectively, we measured systemic and tissue levels of these growth factors in a patient with familial glomangiomas. In addition, we investigated endothelial mitogenicity of the patient's serum as a functional assay of systemic growth factor activity.

Adult↗
PubMed2002

Serum S100 concentrations are not useful in predicting micrometastatic disease in cutaneous malignant melanoma.

BACKGROUND: S100 protein is an acidic calcium binding protein that is expressed by melanoma cells. Elevated serum values of S100 have been described in metastatic disease and it has been suggested that it may be used as an adjunct to staging and monitoring of treatment. Micrometastatic disease in the sentinel lymph node can be demonstrated by sentinel node biopsy (SNB) and the sentinel node status is known to be the most important predictor of relapse. OBJECTIVES: To determine whether serum S100 concentrations could predict the presence of micrometastatic disease. METHODS: Thirty-one patients with primary cutaneous melanoma > 1 mm were recruited from referrals to the Melanoma clinic. All patients had serum S100 concentrations evaluated prior to undergoing SNB. Serum S100 concentrations were established using an immunoluminometric method. Sentinel nodes were identified using a dual technique with both radiolabelled colloid (residual from preoperative lymphoscintigraphy) and blue dye according to the MD Anderson Cancer Center protocol. Results Nine of these 31 patients had evidence of micrometastatic disease on SNB. The mean serum S100 concentration of those with positive SNBs was 0.027 microg L-1 compared with 0.045 microg x L(-1) in patients with negative SNBs (normal < 0.14 microg x L(-1)). No patient in the study demonstrated raised concentrations of serum S100. CONCLUSIONS: We conclude that serum S100 concentrations do not predict the presence of micrometastatic melanoma in sentinel nodes in primary cutaneous melanoma.

Biomarkers, Tumor↗
PubMed2002

Primary cutaneous epidermotropic alveolar rhabdomyosarcoma with t(2;13) in an elderly woman: case report and review of the literature.

We report a case of a primary cutaneous alveolar rhabdomyosarcoma presenting on the lower limb of a 60-year old woman. The tumor was characterized by aggregates of round blue cells in an alveolar growth pattern in the dermis and subcutis, with the additional unique finding of epidermotropism. By immunohistochemistry tumor cells were positive for vimentin, muscle-specific actin, desmin, myogenin, and Myo-D1 with focal positivity for CD56, neuron-specific enolase, and S-100 protein. Staining for pan-keratin, HMB-45, melan-A, epithelial membrane antigen, chromogranin, CD99, leukocyte common antigen, and alpha-smooth muscle actin was negative. Interphase fluorescence in situ hybridization analysis from paraffin-embedded tumor demonstrated the presence of the translocation (2;13)(q35;q14) confirming the diagnosis. Further investigations revealed no tumor in the underlying deep soft tissues, and there was no evidence of metastasis in other organs. A local recurrence associated with a metastasis to a regional lymph node on the right groin was treated with an above-knee amputation and local radiotherapy to the groin area. The patient subsequently developed cutaneous metastases in the amputation stump and died 2 years after initial presentation. This case indicates that rhabdomyosarcoma may rarely present in the skin in adults and should be included in the differential diagnosis of primary cutaneous small round blue cell tumors not only in children but also in this age group.

Chromosomes, Human, Pair 13↗
PubMed2001

Comparison of positron emission tomography scanning and sentinel node biopsy in the detection of micrometastases of primary cutaneous malignant melanoma.

PURPOSE: Sentinel node biopsy (SNB) is a surgical technique for detecting micrometastatic disease in the regional draining nodes. 2-fluorine-18-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) scanning is an imaging technique that can detect clinically undetectable metastases. This prospective study was undertaken to compare the sensitivity of FDG-PET scanning with SNB in the detection of micromatastatic malignant melanoma. PATIENTS AND METHODS: Fifty consecutive patients (23 women, 27 men; mean age, 53 years) with primary melanoma >1 mm thick or lymphatic invasion were recruited (mean, 2.41 mm). Primary lesions had been narrowly excised (<1 cm). Patients underwent PET scanning followed by SNB, using a dual technique. Preoperative lymphoscintigraphy was used to identify the draining basin. Lymph nodes were examined histologically and immunostained for S100 and HMB 45. RESULTS: The sentinel node (SN) was identified in all patients. Fourteen patients (28%) had positive SNBs, including eight patients with melanoma <1.5 mm thick. In none of these 14 patients did PET scans identify metastatic disease in the SN or draining basin. In seven patients, the PET scans were positive in other locations, and in four cases, this was suspicious of metastatic disease. However, no patient has developed recurrent melanoma (mean follow-up, 15 months). All patients with positive SNBs underwent therapeutic lymph node dissection. Further lymph node involvement was found in two patients (primary lesions, 1.3 mm and 3.5 mm thick). CONCLUSION: This study demonstrates the limitations of FDG-PET scanning in staging patients with primary melanoma. SNB is the only reliable method for identifying micrometastatic disease in the regional draining node.

Adult↗
PubMed2001

Localization of a gene (MCUL1) for multiple cutaneous leiomyomata and uterine fibroids to chromosome 1q42.3-q43.

Dominant transmission of multiple uterine and cutaneous smooth-muscle tumors is seen in the disorder multiple leiomyomatosis (ML). We undertook a genomewide screen of 11 families segregating ML and found evidence for linkage to chromosome 1q42.3-q43 (maximum multipoint LOD score 5.40). Haplotype construction and analysis of recombinations permitted the minimal interval containing the locus, which we have designated "MCUL1," to be refined to an approximately 14-cM region flanked by markers D1S517 and D1S2842. Allelic-loss studies of tumors indicated that MCUL1 may act as a tumor suppressor. Identification of MCUL1 should have wide interest, since this gene may harbor low-penetrance variants predisposing to the common form of uterine fibroids and/or may undergo somatic mutation in sporadic leiomyomata.

Chromosome Mapping↗
PubMed2001

Molecular analysis of the immunoglobulin heavy chain gene in the diagnosis of primary cutaneous B cell lymphoma.

The diagnosis of primary cutaneous B cell lymphoma can be difficult on the basis of histologic and immunophenotypic features alone. Previous polymerase chain reaction studies for detection of a clonal population in nodal B cell lymphomas have employed different primer pairs with detection sensitivities varying between 34% and 94% but there have been no comprehensive studies of primary cutaneous B cell lymphoma. We compared the sensitivity of different sets of consensus primers to amplify the CDR3 VDJ region of the immunoglobulin heavy chain gene in combination with an immunoglobulin heavy chain joining region consensus primer to detect a monoclonal population in 39 cases of primary cutaneous B cell lymphoma. Radiolabeled products were analyzed with denaturing 6% polyacrylamide gel electrophoresis. Sequence analysis was used to confirm amplification of clonal immunoglobulin heavy chain gene rearrangements and to establish whether somatic hypermutation can interfere with primer binding. Clonal immunoglobulin heavy chain gene rearrangements were demonstrated in 79% of cases (74% with leader sequences, 64% with FR1, and 45% with FR3 primers). Somatic hypermutation at primer binding sites was confirmed in cases where a false negative result was obtained with the FR3 primer. Although monoplex polymerase chain reaction amplification using the leader sequence primers is the most sensitive method for detecting a clonal population, six primers are required in six different reactions. Our findings suggest initial analysis with the FR3 primer and subsequent analysis using leader sequences in negative cases. Our data indicate that the FR3 consensus primer alone is not sufficient for a comprehensive analysis of primary cutaneous B cell lymphoma.

Base Sequence↗
PubMed2001

Absence of the t(14;18) chromosomal translocation in primary cutaneous B-cell lymphoma.

BACKGROUND: The t(14;18)(q32;q21) chromosomal translocation is found in the majority of nodal follicular lymphomas and in a lower percentage of systemic high-grade diffuse large B-cell lymphomas. The translocation results in the juxtaposition of the bcl-2 gene on chromosome 18 with the immunoglobulin heavy chain joining region on chromosome 14. Bcl-2 protein prevents apoptosis and the translocation leads to overexpression of a functionally normal Bcl-2 protein that prevents apoptosis of neoplastic cells. OBJECTIVES: The purpose of our study was to analyse cases of primary cutaneous B-cell lymphoma (PCBCL) for the presence of the t(14;18) translocation and to correlate the results with Bcl-2 expression and histological subtype. METHODS: Forty-four cutaneous B-cell lymphoid proliferations (36 PCBCL, four follicular B-cell lymphomas with cutaneous presentation and four reactive B-cell infiltrates) were analysed by polymerase chain reaction amplification and polyacrylamide gel electrophoresis using consensus primers for the joining region on the immunoglobulin heavy chain gene in combination with either a primer for the major breakpoint region (MBR) or the minor cluster region (mcr) on chromosome 18. RESULTS: None of 36 PCBCL analysed demonstrated a t(14;18) translocation; however, three of four systemic follicular B-cell lymphomas presenting in the skin were found to have a translocation in the MBR, which was confirmed by sequence analysis. Correlation with Bcl-2 immunostaining showed that of seven patients with high-grade cutaneous diffuse large B-cell lymphoma, four were Bcl-2 positive but had no evidence of a t(14;18) translocation. In the five cases classified as primary cutaneous follicle centre cell lymphoma, the neoplastic cells within the germinal centres failed to express Bcl-2. However, Bcl-2-positive neoplastic cells were present in all four cases of systemic follicular lymphoma, including the case that did not show a t(14;18) translocation. In all cases of marginal zone lymphoma the marginal zone lymphocytes were Bcl-2 positive. CONCLUSIONS: These findings indicate that the t(14;18) translocation does not occur in PCBCL, which suggests the involvement of different pathogenetic mechanisms compared with their nodal counterparts. Furthermore, the detection of a t(14;18) translocation in cutaneous B-cell lymphoma should suggest the presence of systemic disease, which underlies the need for exhaustive staging procedures.

Chromosomes, Human, Pair 14↗