PubMed Health⌕ Search

Biomedical subjects

J M Theaker

Publications and source records attributed to J M Theaker.

At least 19 recordsLinked to original sources
PubMed1999

The value of central histopathological review of testicular tumours before treatment.

OBJECTIVE: To assess the value of central histopathological review of testicular tumours. MATERIALS AND METHODS: The histopathology reports of the referring hospital and central review were compared for all referred testicular specimens (201 orchidectomies and seven testicular biopsies) from 11 hospitals in one region, between 1992 and 1997. RESULTS: There were two main findings: First, there was a major discrepancy of tumour type in 12 specimens (6%). The most frequent change (in five cases) was from seminoma to nonseminomatous germ cell tumour (NSGCT). There were also difficulties with uncommon tumours such as spermatocytic seminoma, lymphoma and adenocarcinoma. Treatment was changed as result of the altered diagnosis in eight of these 12 patients. Second, there were discrepancies of interpretation of vascular invasion in 12 of 59 NSGCTs (20%). Differences of tumour elements recognized in NSGCTs were frequent. CONCLUSIONS: The errors discovered on central histopathological review of testicular tumours were significant, though small in number. This supports the idea of central review and is consistent with the specialization recommended in the Calman-Hine cancer arrangements.

Biopsy↗
PubMed1999

Polymerase chain reaction based human leucocyte antigen genotyping for the investigation of suspected gastrointestinal biopsy contamination.

BACKGROUND: Mislabelling or contamination of surgical specimens may lead to diagnostic inaccuracy, particularly within gastrointestinal pathology when multiple small mucosal biopsy specimens are commonly taken, and where a tiny fragment of foreign tissue may be indistinguishable from true biopsy material using histological assessment alone. AIMS: To assess the utility of polymerase chain reaction (PCR) based human leucocyte antigen (HLA) genotyping techniques for the investigation of potentially mislabelled or contaminated gastrointestinal biopsy specimens. PATIENTS: Ten cases (28 samples) in which mislabelling or contamination was suspected, comprising four upper gastrointestinal tract biopsies and six colonoscopic biopsy series. METHODS: Direct and nested PCR-sequence specific primer (SSP) based HLA class II genotyping was performed on DNA extracted from formalin fixed and paraffin wax embedded tissue (23 samples) or peripheral blood leucocytes (five samples). RESULTS: A full HLA-DRB1 genotype was determined in all 28 samples. In seven cases the HLA-DRB1 genotype of the putative contaminant was different to that of the corresponding reference tissue, confirming different individual origins for the contaminant and reference material. In one case the contaminant tissue was shown to possess the same HLA-DRB1 alleles as a second patient (probable source). In the remaining three cases the same HLA-DRB1 alleles were detected within the potential contaminant and reference tissues. CONCLUSIONS: PCR based HLA class II genotyping is a valuable tool for investigating potential contamination or mislabelling within gastrointestinal biopsy specimens and this report has confirmed contamination in seven of ten cases studied.

Adult↗
PubMed1998

Malignant melanoma re-excision specimens--how many blocks?

AIMS: Wide local excision is commonly undertaken as part of the further management of cutaneous melanoma. Although the original excision is usually complete, pathologists vary considerably in their macroscopic handling and sampling of the wide excision specimens. This study evaluates the sampling of reexcision specimens and the information gained from histological examination of tissue blocks in order to develop guidelines for the handling of these specimens. METHODS AND RESULTS: The study group comprises 219 cases of melanoma which underwent initial biopsy followed by wider excision. The macroscopic appearance, number of blocks taken and presence of residual melanoma in the wide excision specimen was assessed. Residual melanoma was detected in the wide excision specimen in only four cases out of the 167 in which the original melanoma had been described as completely excised and in these cases the detection of a residual lesion reflected either advanced local disease at the time of the original excision, or an incompletely excised extensive radial growth phase. The sampling of wide excision specimens varied (range of blocks 1-12, average 3.1) but statistical analysis showed no undersampling of the wide excision specimens in which no residual lesion was found. CONCLUSIONS: These results show that detection of a residual lesion in wide excision specimens of melanomas previously completely excised is unusual and offers no additional clinically useful information. Random block taking in the absence of a macroscopic abnormality is therefore unlikely to be clinically useful. Guidelines for the gross handling of these wide excision specimens are proposed which are likely to save resources in most histopathology departments by reducing block numbers.

Humans↗
PubMed1998

HLA-DQB1*0303 and *0301 alleles influence susceptibility to and prognosis in cutaneous malignant melanoma in the British Caucasian population.

The presence of lymphocytic infiltrates within primary cutaneous malignant melanoma (CMM), documented spontaneous tumour regression and genetic linkage with chromosome six in familial cases all suggest that immunogenetic factors may modulate disease progression. An association has been suggested between HLA DQB1*0301 and CMM in US patients but no such investigation has been performed in the UK population. Polymerase chain reaction-based HLA class II DRB1, DQA1 and DQB1 typing of 99 UK-based CMM patients was performed using DNA extracted from archival formalin-fixed and paraffin wax-embedded surgical biopsies, enabling retrospective access to clinical follow-up data. An increase in frequency of the HLA DQB1*0303 genotype among CMM patients was identified compared to control subjects (19.2% vs 5.8%; Pc=0.003; RR=3.9) while HLA DQB1*0301 was associated with more advanced and therefore poorer prognosis primary tumours (e.g. HLA DQB1*0301 allele frequency: 20.1% vertical growth phase vs 4.0% horizontal growth phase; Pc=0.03; RR=6.1). These findings suggest that the HLA DQB1 locus, and in particular the HLA DQB1*0303 and *0301 alleles, may play an important role in determining the risk of development and the prognosis of CMM within the UK population.

Female↗
PubMed1997

The growing teratoma syndrome in a nongerminomatous germ cell tumor of the pineal gland: a case report and review.

BACKGROUND: The growing teratoma syndrome is a recognized complication of metastatic nonseminomatous germ cell tumors of the testis and is managed surgically. It may also occur in intracranial nongerminomatous germ cell tumors. METHODS: The authors performed an English language computer search using the EMBASE data base (from January 1980 to December 1996) for pineal tumors, read all abstracts, and then selected all articles pertaining to germ cell tumors at this site. RESULTS: The case history of a 19-year-old male who presented with a pineal nongerminomatous germ cell tumor, which was treated with chemotherapy, is reported. Despite normalization of raised tumor marker levels, the pineal mass enlarged during chemotherapy. This was excised and proved to be a mature teratoma. A review of the literature regarding this complication of intracranial germ cell tumors is also presented. CONCLUSIONS: The authors believe this to be the first reported case of growing teratoma syndrome in the pineal gland of an adult patient, two previously reported cases occurred in children. The authors conclude that the pineal gland is an unusual but important site in which to recognize the growing teratoma syndrome.

Adult↗
PubMed1997

Nested polymerase chain reaction-based HLA class II typing for the unique identification of formalin-fixed and paraffin-embedded tissue.

Human leukocyte antigen (HLA) genotyping is routinely performed prior to organ transplantation using peripheral blood leukocyte-derived DNA. In addition, polymerase chain reaction (PCR)-based methods have permitted HLA genotyping using DNA extracted from formalin-fixed and paraffin-embedded tissue, with proven applications in HLA-disease association studies and surgical biopsy identification. The utility of current techniques may be limited by the poor yield of intact DNA from such paraffin biopsies. This paper describes a new nested PCR-based HLA class II genotyping method which reliably detects HLA DRB alleles within DNA extracted from even extremely small paraffin biopsies. This method comprises initial PCR amplification of exon II sequences of the HLA DRB1, 3, 4, and 5 genes using generic PCR primers. Identification of the HLA DRB1 alleles and detection of the DRB3, 4, and 5 genes is then performed using a series of separate individual second-round PCR reactions, each of which contains PCR primer pairs detecting a single HLA DRB allele or group of alleles (PCR-SSP). The ability of this method to detect 19 individual HLA DRB1 alleles or groups of alleles, covering all common DRB1 specificities, was confirmed via concordant results when compared with 'direct' (single amplification step) PCR-SSP analysis of one cell line-derived and nine peripheral blood-derived DNA samples, and with five DNA samples extracted from paraffin biopsies. The technique was then successfully applied to 11 further paraffin biopsy-derived DNA samples, of which ten were untypable by 'direct' PCR-SSP analysis, from five cases in which doubt existed as to the individual origin of the tissues.

Adult↗
PubMed1997

Genetic analysis of hydatidiform moles in paraffin wax embedded tissue using rapid, sequence specific PCR-based HLA class II typing.

AIMS: To determine the applicability of rapid, sequence specific polymerase chain reaction (PCR)-based HLA class II genotyping for the distinction of complete from partial hydatidiform moles (HM) using DNA extracted from formalin fixed and paraffin wax embedded tissue. METHODS: Nine HM were studied. DNA was extracted from formalin fixed and paraffin wax embedded tissue after mechanical separation of decidual and molar components. HLA class II DRB (DRB1, -3, -4, and -5) and DQB1 genotyping was performed using a parallel series of PCR reactions, each of which contained sequence specific primers designed to amplify different HLA DRB and DQB1 alleles or allele groups (PCR-SSP analysis). In each case the HLA DRB and DQB1 genotypes identified within the decidua and HM were compared. RESULTS: Within the decidual tissue, HLA DRB genotypes were assignable in all nine cases, and HLA DQB1 genotypes were identified in seven cases. Within the molar tissue, HLA DRB genotypes were assignable in seven cases, and at least one HLA DQB1 allele was identified in seven cases. Interpretation based on HLA class II genotyping was therefore possible in two cases classified on histological appearances as complete HM, in four classified as partial HM, and in one HM of uncertain type. Different HLA DRB and DQB1 haplotypes were identified within the decidual and molar tissue from both complete HM, consistent with a solely paternal origin and supporting the histological diagnosis. HLA DRB and DQB1 alleles common to the decidual and molar tissue were present within the four partial HM and the HM of histologically uncertain type, consistent with combined maternal and paternal genetic input to these HM, supporting the histological diagnosis in four cases and suggesting that the histologically equivocal case was also a partial HM. CONCLUSION: PCR-SSP HLA class II DRB and DQB1 typing is reliably applicable to DNA extracted from formalin fixed and paraffin wax embedded tissue. Therefore, in a suitably equipped HLA typing laboratory, this technique provides a useful adjunct to histological examination for differentiation of complete from partial HM.

Alleles↗
PubMed1996

Investigation of specimen mislabelling in paraffin-embedded tissue using a rapid, allele-specific, PCR-based HLA class II typing method.

Mislabelling of surgical specimens can seriously affect the accuracy of histopathology reports. We describe two cases in which clinically suspected mislabelling was investigated by polymerase chain reaction (PCR)-based HLA DRB and DQB tissue typing of paraffin biopsy-derived DNA, using sequence specific primers (PCR-SSP HLA typing). In the first case, two patients underwent surgery for breast carcinoma. A subcutaneous lymph node containing metastatic carcinoma was received with the breast specimen from one patient, but was clinically considered more likely to originate from the other patient who underwent breast surgery on the same day. In the second case, histological examination of retained products of conception from a young woman revealed adenocarcinoma, but a repeat curettage specimen consisted of secretory phase endometrium. In case 1, PCR-SSP HLA typing confirmed the clinical suspicion that the subcutaneous lymph node received with tissue from one patient originated from the other patient. This result converted the first patient from lymph node positive breast carcinoma to lymph node negative disease. In case 2, there was no evidence from PCR-SSP HLA typing that the endometrial samples had originated from different patients. PCR-SSP HLA typing requires fewer steps than methods based on PCR amplification followed by oligonucleotide probing (PCR-SSOP HLA typing), and relies on the amplification of shorter sequences of DNA. Therefore, this technique can produce more rapid results than PCR-SSOP HLA typing, and is ideally suited to typing partially degraded DNA derived from formalin-fixed and paraffin-embedded tissue.

Adenocarcinoma↗
PubMed1996

The evaluation of diagnostic and prognostic criteria and the terminology of thin cutaneous malignant melanoma by the CRC Melanoma Pathology Panel.

Sections from 95 skin lesions excised at pigmented lesion clinics in England and Scotland were studied by eight histopathologists in order to evaluate consistency in the use of histopathological terms for features of diagnostic and prognostic importance for cutaneous malignant melanoma. The level of agreement (kappa) amongst the panel improved after discussion and re-definement of criteria for several features. These included, architectural and nuclear atypia, pagetoid infiltration and radial and vertical growth phases. A high level of agreement was achieved for an overall benign or malignant diagnosis (kappa = 0.77) but use of more specific terms such as benign naevi with atypia and melanoma < or = 0.76 mm thickness, was associated with only an intermediate level of agreement. Of the original diagnosis of melanoma, 17% were re-classified by the panel as benign with atypia and 2% reported to be benign were judged to be melanoma. This reflected the high proportion of borderline lesions in the study. The use of standardized diagnostic criteria with precise definitions has been shown to improve consistency in diagnosis and it is recommended for general application. From this should emanate more reliable incidence figures for thin melanoma, and improved understanding of the nature of these early lesions, to the benefit of patient and clinician alike. The poor concordance in distinguishing severe dysplasia in the junctional component of melanocyte proliferations from melanoma in situ and superficial dermal invasion improved only modestly despite intensive efforts. Since melanoma in situ and severe dysplasia cannot be distinguished by objective measurements and since their clinical management is the same, the panel suggests that attempts to separate them in diagnostic reports should be discontinued and they could both be referred to as melanocytic intraepidermal neoplasia (MIN). If it becomes accepted that dermal invasion without a vertical growth component can also be managed identically to MIN, then this invasive radial phase may be appropriately referred to as microinvasion and linked to MIN for the purposes of clinical management.

Biopsy↗
PubMed1996

CD45RO and CD45RA positive cell populations in idiopathic membranous and IgA glomerulopathy.

AIMS: To immunophenotype and quantitate glomerular and interstitial inflammatory cells in cases of idiopathic membranous and IgA glomerulopathy; to correlate cell numbers with aspects of clinical data and renal function. METHODS: Routine indirect immunoperoxidase staining was performed on frozen section renal biopsy specimens for T and B lymphocyte related antigens, macrophages and MHC class II antigens. Double immunohistochemical staining was performed to identify CD45RO+ and CD45RA+ cells. RESULTS: In IgA glomerulopathy correlations were found relating interstitial cell numbers to creatinine concentration at biopsy (CD45RO+ and CD45RA+ cells) and follow up creatinine concentration (CD3+, CD4+, CD8+, CD45RO+, and CD45RA+ cells). Also in IgA glomerulopathy mean arterial pressure at biopsy correlated with interstitial cell numbers and most recent follow up creatinine concentration. There were no correlations between glomerular inflammatory cells and renal function in either disease. Double staining showed that although most glomerular CD45RO+ and CD45RA+ cells were macrophages, positive cells in the interstitium were lymphocytes. The interstitial CD45RO+:RA+ ratio in normal renal biopsy specimens was approximately 5:1; for IgA glomerulopathy it was 1.5 and was 1.0 in idiopathic membranous glomerulopathy. CONCLUSIONS: This study demonstrates that interstitial, and not glomerular, inflammatory cell numbers correlate with renal function in primary glomerular disease and that double staining is necessary to interpret positive immunostaining for antigens located on more than one type of inflammatory cell. Detailed investigation of the interstitial CD45RO+ and CD45RA+ cells may give an insight into the pathogenesis of glomerular disease.

Adolescent↗