Langerhans cells in odontogenic tumours and cysts as detected by S-100 protein immunohistochemistry

Immunohistochemical demonstration of S-100 protein in Langerhans cells (LCs) was made in odontogenic epithelial tumours (71 cases), radicular cysts (40 cases), follicular cysts (28 cases), odontogenic keratocysts (11 cases), primordial cysts (7 cases) and fissual cysts (6 cases). With the use of polyclonal antiserum against S-100 protein, positive LCs, dendrical or irregular in shape were found in tumour or cystic epithelia, and sometimes in stromal connective tissue. Incidence of positive S-100 staining LCs was 11 cases out of 61 ameloblastomas, 22 cases out of 40 radicular cysts, 3 cases of 28 follicular cysts, and other lesions in both odontogenic tumours and cystic diseases lacked LCs. The cases with S-100 protein positive LCs were usually accompanied with a high degree of inflammatory infiltration in their lesions; on the contrary, the negative cases also generally lacked inflammatory responses.     

Fine needle aspiration cytology in ovarian lesions: an institutional experience of 584 cases

N. Gupta, A. Rajwanshi, L. K. Dhaliwal, N. Khandelwal, P. Dey, R. Srinivasan and R. Nijhawan
Fine needle aspiration cytology in ovarian lesions: an institutional experience of 584 cases Objective: To assess the diagnostic value of fine needle aspiration cytology (FNAC) in ovarian lesions. Methods: This was a retrospective study of ultrasound‐guided (US) FNAC of 584 ovarian lesions from January 1998 to July 2010. The lesions were categorized into non‐neoplastic lesions, neoplastic lesions and inadequate aspirates. The results were compared with the corresponding histopathology whenever available. Results: Of the 584 lesions, 180 (30.8%) were reported as non‐neoplastic (48 non‐specific inflammation, 11 tuberculosis, 63 functional cysts and 58 endometriotic cysts), 249 (42.6%) as neoplastic (81 benign lesions/tumours and 168 malignant) and 155 (26.5%) as inadequate. Based on the subsequent histopathology, which was available in 121 (20.7%), the cases were divided into those that were concordant and discordant. Concordant cases comprised 92/121 (76%), including 28 non‐neoplastic lesions (seven non‐specific inflammation, nine functional cysts and 12 endometriotic cysts), 42 surface epithelial tumours (13 benign and 29 malignant), 10 germ cell tumours (five mature cystic teratomas and five mixed germ cell tumours), seven sex‐cord stromal tumours (three granulosa cell tumours, one sclerosing stromal tumour, one strümal leutoma, one Sertoli Leydig cell tumour and one malignant Sertoli cell tumour) and five miscellaneous lesions (one plasma cell tumour, two leiomyosarcomas and two cases of necrosis). Discordant cases comprised 29/121 (24%) (21were inconclusive or inadequate on cytology), including four endometriotic cysts, 14 surface epithelial tumours (one cystadenofibroma, one borderline mucinous tumour and 12 carcinomas), five germ cell tumours (two immature teratomas and three mature cystic teratomas), two thecomas, one fibroma, one sclerosing stromal tumour, one fibrosarcoma and one myxoma. FNAC sensitivity for a diagnosis of malignancy was 85.7%, specificity 98.0%, positive predictive value 97.7%, negative predictive value 87.7% and accuracy 92.0%, if 21 inconclusive/inadequate FNACs were excluded; with the latter taken as false negatives, sensitivity was 73.7% and accuracy 76.0%. Conclusion: FNAC has a high specificity for diagnosis of ovarian/adnexal lesions but greater experience is required for the accurate subtyping of neoplasms and sensitivity is limited by inconclusive/inadequate results.     

Transforming growth factor β , (TGFβ) secreted by immunogenic ex vivo human carcinoma cells, counteracts the activation and inhibits the function of autologous cytotoxic lymphocytes. Pretreatment with interferon γ and tumor necrosis factor α reduces the production of active TGFβ

 We present the results obtained with an in vitro model system that resembles the in vivo tumour microenvironment, where malignant cells are in close contact with the infiltrating lymphocytes. Unmanipulated blood lymphocytes were cytotoxic against the autologous ex vivo tumour cells in 3/19 patients and this function was generated in 6-day mixed cultures in five additional cases. Production of transforming growth factor β (TGFβ) by the freshly separated tumour cells was determined in parallel. Cytotoxicity was generated by a small number of tumour cells (2–5/100 lymphocytes), while a large number (10–20/100 lymphocytes) inhibited not only the generation but also the existing lytic activity. The presence of a neutralising TGFβ-specific mAb (2G7) potentiated the activation of lymphocytes and suspended the suppression inflicted by the tumour cells. In those tumours, which expressed relatively high levels of MHC class I and ICAM-1 molecules, the quantity of secreted TGFβ interfered with the ability of tumour cells to generate cytotoxic lymphocytes. In the tumours with low expression of class I, such a correlation was not detected, indicating the primordial role of MHC class I expression in the regulation of autologous tumour recognition. Our results demonstrate the involvement of TGFβ in the impaired lymphocyte-mediated reactivity against immunogenic tumours and support a mechanism that contrasts the tolerance or anergy. Since presence of TGFβ in the microenvironment of tumours counteracts the function of cytotoxic T lymphocytes, production of this cytokine can contribute to the failure of immunotherapy. Received: 19 June 1997 / Accepted: 14 August 1997     

Loss of heterozygosity on chromosome 11p13 in primary bladder carcinoma

Although the occurrence of bladder cancer is common, the molecular events underlying the pathogenesis of this cancer remain ill-defined. A loss of heterozygosity (LOH) at specific chromosomal loci may predispose individuals to the development of bladder cancer but this has not been examined in detail. Furthermore, the role that deletion or inactivation of putative tumour suppressor genes might play in the genesis of bladder cancer has not been established. In this study, allelic deletion analysis on the short arm of chromosome 17 of patients with primary bladder tumours failed to show deletion at 17p13 (0/7), a region known to contain the p53 tumour suppressor gene. Chromosome 11p15 showed allelic deletion at the IGF2 locus (2/7: 29%) and the PTH locus (1/11: 9%). However, no deletion was observed at the CALCA locus (0/6). LOH at 11p13, a region containing the Wilm's tumour suppressor gene (WT1), was also studied. Analysis of LOH at 11p13 showed deletion at the CAT locus (13/18: 72%), the J/D11S414 locus (5/15: 33%), the WT1 locus (7/14: 50%) and the FSHB locus (6/16: 38%). The significance of these findings is discussed.     

Familial adenomatous polyposis-associated desmoids display significantly more genetic changes than sporadic desmoids

Desmoid tumours (also called deep or aggressive fibromatoses) are potentially life-threatening fibromatous lesions. Hereditary desmoid tumours arise in individuals affected by either familial adenomatous polyposis (FAP) or hereditary desmoid disease (HDD) carrying germline mutations in APC. Most sporadic desmoids carry somatic mutations in CTNNB1. Previous studies identified losses on 5q and 6q, and gains on 8q and 20q as recurrent genetic changes in desmoids. However, virtually all genetic changes were derived from sporadic tumours. To investigate the somatic alterations in FAP-associated desmoids and to compare them with changes occurring in sporadic tumours, we analysed 17 FAP-associated and 38 sporadic desmoids by array comparative genomic hybridisation and multiple ligation-dependent probe amplification. Overall, the desmoids displayed only a limited number of genetic changes, occurring in 44% of cases. Recurrent gains at 8q (7%) and 20q (5%) were almost exclusively found in sporadic tumours. Recurrent losses were observed for a 700 kb region at 5q22.2, comprising the APC gene (11%), a 2 Mb region at 6p21.2-p21.1 (15%), and a relatively large region at 6q15-q23.3 (20%). The FAP-associated desmoids displayed a significantly higher frequency of copy number abnormalities (59%) than the sporadic tumours (37%). As predicted by the APC germline mutations among these patients, a high percentage (29%) of FAP-associated desmoids showed loss of the APC region at 5q22.2, which was infrequently (3%) seen among sporadic tumours. Our data suggest that loss of region 6q15-q16.2 is an important event in FAP-associated as well as sporadic desmoids, most likely of relevance for desmoid tumour progression.     

Sellar Masses That Present With Severe Hyponatremia

ObjectiveHyponatremia is a known but underrecognized presentation of sellar lesions. Herein, we present a series of patients who presented with single or multiple episodes of hyponatremia.MethodsOver 5 years, patients undergoing endonasal surgery for a de novo sellar mass with hyponatremia as an initial presentation were included. Pathology, sodium levels, pituitary hormonal status, and treatment course were documented.ResultsOf 282 patients, 16 (5.7%) (9 males, 7 females, age 32 to 84 years) presented with severe hyponatremia, with a mean serum sodium level of 115 ± 6 mmol/L (range, 101 to 125 mmol/L), and 3 patients had 2 or more episodes. Severe hyponatremia was a presenting sign in 0, 4.1, 14.3, and 37.5% of patients with craniopharyngiomas (n = 10), pituitary adenomas (n = 243), Rathke’s cleft cysts (RCCs) (n = 21), and sellar arachnoid cysts (n = 8), respectively (P < .01). Half of the patients presenting with hyponatremia, including 6 of 10 patients with adenomas and 2 of 3 patients with RCCs, had pituitary apoplexy or cyst rupture. All patients had anterior pituitary gland dysfunction, including 81% with hypoadrenalism and 69% with hypothyroidism. Following surgery, hormonal status was unchanged or improved in 15 patients (median follow-up, 14 months). No patient had tumor/cyst recurrence or recurrent hyponatremia.ConclusionSevere hyponatremia was a presenting sign in 5.7% of patients with sellar pathology, most frequently in patients with arachnoid cysts, RCCs, and pituitary apoplexy. Patients with new-onset severe hyponatremia and no obvious pharmacologic or systemic cause should undergo pituitary hormonal evaluation and brain imaging. Surgical resection and correction of hormonal deficiencies are associated with resolution of recurrent hyponatremic episodes. (Endocr Pract. 2014;20:1178-1186)     

Cases with manifestation of <Emphasis Type="Italic">chemodectoma</Emphasis> diagnosed in dogs in Department of Internal Diseases with Horses,Dogs and Cats Clinic,Veterinary Medicine Faculty,University of Environmental and Life Sciences,Wroclaw, Poland

In the period of 3 years, 9 tumours of chemodectoma were supravitally diagnosed and histopathologically verified in dogs. In this period 15 351 dogs were admitted to the Clinic of Dogs and Cats and 2 145 dogs were examined in the cardiological outpatient clinic for dogs. This tumour is located in a typical place - at the base of the heart. Most frequently the tumour manifested in older boxers. Only in one case such a tumour was diagnosed in another breed of dogs. The tumours ranged in size between 3 and 16 cm in diameter. The principal sign accompanying tumours of cardiac base involved dyspnoea but in 3 cases the tumours yielded no clinical signs. All the diagnoses were additionally verified using immunohistochemical examination. We used antibodies to chromogranin A (clone DAK-A3 1:100), synaptophysin (clone SY38 1:20) and neuron-specific enolase (clone BBS/NC/VI-H14 1:150). An immunohistochemical examination is vital for the diagnosis since it allows to differentiate histologically distinct types of neoplasia which may locate in the same site and may manifest a similar histological pattern.     

Ultrasound biomicroscopy examination of tumors of the iris and ciliary body

The ultrasound biomicroscope (UBM) has a major role in detecting and following different types of intra-ocular masses in the anterior part of the eye. This equipment may provide the possibility to detect the inner structure of the masses, to differentiate between cysts and solid tumours, and to follow their progression and spreading into the surrounding tissue. In the last six years 30 patients with iris and ciliary body tumour were found in our laboratory. The examination were performed by Zeiss Humphrey Ultrasound Biomicroscope, Model 840, 50 MHz probe. We followed closely 22 patients. Surgical removal and histological examination were performed in 3 cases. Melanocytoma, retinoblastoma and ring melanoma were revealed. Although the symptoms of the anterior uveal tumours are uncommon, and these tumours show very slow progression, early detection and regular follow-up is needed. In the case of tumour progression the UBM has an important role in planning and timing of surgery or radiotherapy, which can have a favourable effect on the outcome of the disease.     

Expression of the membrane complement regulatory protein CD59 (protectin) is associated with reduced survival in colorectal cancer patients

It has been known for some time that the immune system can recognise growing tumours, and that tumours may respond by modulation of molecules, which make them resistant to further attack. Expression, over-expression, or loss of these molecules may function as markers of tumour progression and prognosis. Among such molecules are the membrane-bound complement regulatory proteins (mCRP), which protect cells from bystander attack by autologous complement. These include CD59 (protectin), which prevents formation of the MAC complex in the terminal stages of complement activation. In the present study, we evaluated immunohistochemical expression of CD59 in a series of over 460 well-characterised colorectal cancers using tissue microarrays (TMA), and related this information to known tumour and patient variables and to survival. The CD59 expression was observed in 69 (15%) of cases overall, and was significantly associated with tumour grade. In contrast, no associations were noted with tumour site, stage or histological type. On survival analysis, a further correlation was observed between expression of CD59 by the colorectal tumours and a reduction in disease-specific patient survival. This observation was strongest for patients with early stage disease. However, a negative impact on survival was also seen in those patients with late stage disease. These results indicate that TMA linked to good clinicopathological databases with good long term follow up are useful tools for determining new prognostic indicators that can be used in future patient management. Immune surveillance may result in immune–editing that induces variable expression of a range of target antigens, and these may be useful prognostic markers. This study has identified CD59 expression as a marker of poor prognosis in colorectal cancer patients.This article is a symposium paper from the "Robert Baldwin Symposium: 50 years of Cancer Immunotherapy", held in Nottingham, Great Britain, on 30th June 2005.     

Needling renal cysts and tumours: cytology and radiology.

Renal masses found by intravenous urography, ultra-sound scanning, and arteriography were needled in 102 patients. Simple renal cysts containing clear fluid and no cytological abnormalities were found in 85 patients. Two unsuspected renal cell carcinomas were found on puncture; cytological examination showed malignant cells in the aspirate. Another five renal tumours were needled deliberately before nephrectomy, and a firm preoperative diagnosis of renal cell carcinoma was made on aspiration cytology in three. Benign cysts which had bled were particularly hard to diagnose. With care, radiology and cytology in combination can provide the firm diagnostic base needed for sound clinical management. The radiology-cytology team must be alert to the unusual finding that indicates a complex lesion, such as an unsuspected renal tumour.     

Lung resistance protein analysis in testicular cancer

Germ cell testicular cancers are well-curable neoplasms, because total remission can be achieved in about 80% of the cases. However, 15-20% of the patients die due to drug resistance (DR). A number of mechanisms of the multidrug resistance phenotype are known, including MDR/P-glycoprotein (P-gp) and the so-called multidrug resistance associated protein (MRP). Lung Resistance Protein (LRP) is an ATP dependent membrane transporter protein associated with MDR. In our present work we studied the expression of LRP in testicular cancers. LRP expression was determined by immunohistochemistry (IH), Western blot (WB) and RT-PCR techniques. Clinical resistance was defined in accordance with the clinical oncologic rules. In 29 (41%) of 70 primary testicular tumours and in 22 (63%) of 35 cases, elevated LRP levels were established by IH and WB, respectively. In the latter 63%, the LRP mRNA levels were elevated as well. Six cases of the 15 seminomas and 23 cases of the nonseminomatous germ cell tumours (NSGCT) proved to be positive. No relationship was demonstrated between LRP expression and the stage of the disease. Despite the LRP positivity of 6 tumour samples, all of the seminomas proved sensitive. Of the 39 sensitive NSGCT, 27 cases were LRP-negative, whereas 11 tumour samples of 16 patients belonging to the resistant group proved LRP-positive (p=0.04). The authors concluded that the expression of LRP is responsible for clinical drug resistance in non-seminomatous testicular cancer patients.     

Molecular nature of genetic changes resulting in loss of heterozygosity of chromosome 11 in Wilms' tumours

Summary In this paper we describe the analysis of genetic changes in chromosome 11 in Wilms' tumours. Using a range of probes for regions 11p15, 11p13 and 11q we have screened DNA from 14 Wilms' tumours together with control DNA obtained from the patients' lymphocytes and their parents. We have been able to demonstrate loss of heterozygosity in 5 of the 14 different Wilms' tumours. In three of these five tumours, loss of heterozygosity did not involve markers for 11p13, 11p15.4 or the proximal region of 11p15.5, but only some markers assigned to the most distal part of 11p15.5. In two of these tumours we could demonstrate unequal mitotic recombination in 11p with breakpoints in the hypervariable regions 5 of the insulin gene and/or 3 of the HRASI protooncogene. In one tumour, from a Beckwith-Wiedemann patient, all markers for the region 11a13-pter became hemizygous; the region 11q13-qter remained heterozygous. These results demonstrate that loss of heterozygosity in Wilms' tumours may not necessarily involve the proposed Wilms' tumour locus at 11p13 but may be limited to 11p15.5. This suggests that not only the 11p13 region, but also the 11p15.5 region is involved in Wilms' tumour development. The possible role of both regions in the development of Wilms' tumour is discussed.     

The polysaccharide K (PSK) potentiates in vitro activation of the cytotoxic function in human blood lymphocytes by autologous tumour cells

Summary We have studied the effect of polysaccharide K (PSK) in the in vitro recognition of ex vivo carcinoma, sarcoma and lymphoma cells by the autologous blood lymphocytes. In 4/25 experiments PSK treatment activated the lymphocytes for auto-tumour lysis. Tumour cells alone generated lytic activity both in short- (16 h) and in longterm (6 days) mixed lymphocyte/tumour cell cultures (MLTC), in 2/12 and 3/13 cases respectively. The tumours that activated the lymphocytes expressed high levels of major histocompatibility complex (MHC) class I molecules. In vitro cytokine (interferon and tumour necrosis factor ) treatment of the tumour cells elevated the amounts of class I antigens and the treated cells acquired stimulatory potential. When PSK was added to the MLTC, in which untreated tumour cells were used, lytic potential was induced in 9/13 short-term and in 11/12 long-term cultures. It is noteworthy that in the presence of PSK the untreated, negative or low-class-I-expressor tumours also activated the cytotoxic function of the lymphocytes in 4/5 long-term and in 6/7 short-term cultures. Even in the case of those lymphocytes that could be activated by PSK or tumour cells alone, the simultaneous exposure was more efficient. The effect of PSK was dose-dependent, being optimal at 1 µg/ml and 10 µg/ml. The presence of EDTA and/or cytochalasin B in the cytotoxic test performed with the activated effectors abrogated the lysis, indicating the requirement of contacts with the effector cells.     

Colorectal cancer diagnosis by a direct leukocyte migration test using a panel of tumour extracts

Summary In a direct leukocyte migration test, peripheral blood leukocytes were pulsed with a high dose (2.5 and 0.5 mg/ml) of 3 M KCl extracts from 5 different colorectal tumours as well as with one 3 M KCl extract of normal colonic mucosa. Patients showing a pathological migration index (0.80 and 1.17), with 3 or more out of 5 tumour extracts, were considered as positives.With this test mode 93% (55/59) of patients with colorectal carcinomas were reactive, irrespective of the tumour stage, while only 7% (2/27) of patients with non-malignant colorectal diseases showed a positive reaction. Patients with malignant and non-malignant diseases of other organs were reactive in 2–3% of cases. No positive reactivity was observed with leukocytes from 37 healthy volunteers. Pulsing leukocytes with the normal colonic mucosal extract, a pathological migration index was found in about 20% of colorectal cancer patients, but not in healthy volunteers.Evaluating 10 single tumour extracts individually, reactivity of cancer patients' leukocytes ranged from 65–89% of tests, the difference being not statistically significant. Leukocytes from healthy volunteers showed a pathological migration index with the different extracts in 0–6% of tests.With the leukocyte migration test we could not differentiate between tumours of the colon, sigma or rectum. Patients bearing tumours in any part of the large bowel showed pathological leukocyte migration with extracts of colon-, sigma- and rectum tumours. When the cross-reactivity study was extended to tumours of the gastrointestinal tract, it was found that patients with colorectal tumours were reactive, in a high percentage of tests, with extracts of gastric tumours, but gastric as well as oesophageal and pancreatic cancer patients' leukocytes only reacted occasionally with colorectal tumour extracts.In the follow-up study, a positive reactivity was still found 10–14 days after surgery in 27/31 patients. After more than 2 months, the frequency of positive reactivity decreased to 10/70 cases. Patients with local recurrence or metastases exhibited positive reactivity in 6/7 cases.Abbreviations LMT leukocyte migration test - LM leukocyte migration - LMI leukocyte migration inhibition - LME leukocyte migration enhancement - MI migration index     

Localisation and expression of aquaporin subtypes in epithelial ovarian tumours

To characterise AQP subtype localisation and expression in epithelial ovarian tumours, immunohistochemistry was used to assess the localisation and expression of AQP1-9 in 30 benign tumour cases, 30 borderline tumour cases, 50 malignant tumour cases and 20 normal ovarian tissue cases. Multiple AQP subtypes were expressed in epithelial ovarian tumours, with each AQP subtype displaying a different pattern of localisation and expression. AQP1 was mainly expressed in the microvascular endothelium, and AQP 2-9 were mainly expressed in tumour cells. Most AQP subtypes co-localised in the basolateral membranes of the epithelia of benign tumours and plasma membranes of malignant tumour cells. The positive rates for AQP1, 5, 6, 7, 8, and 9 were over 50%, but those for AQP2, 3 and 4 were only 10-40%. The expression of AQP1, 5 and 9 in malignant and borderline tumours was significantly higher than that in benign tumours (P<0.05) and normal ovarian tissue (P<0.05). However, AQP6 expression in ovarian malignant and borderline tumours was significantly lower than that in benign tumours (P<0.01) or normal ovarian tissue (P<0.01). AQP1 expression was increased in cases with ascites volumes greater than 1000 mL (P<0.05), AQP5 expression was greater in cases with lymph node metastasis (P<0.05), and more AQP9 expression was observed in G3 cases versus G1 and G2 cases (P<0.01). These results suggest that changes in the distribution and expression of AQP subtypes may be involved in ovarian carcinogenesis. This study presents a novel avenue of research that could illuminate the mechanism of ovarian carcinogenesis and treatment.     

Diagnostic potentials of computed tomography in tumors of the thymus

115 patients with different morphological thymus lesions, including 67 with thymoma have been examined on a computer tomograph "Somatom DR-2" ("Siemens", FRG). Characteristic features of hyperplasia and thymus cysts, as well as benign and malignant thymus tumours have been revealed by computer tomography (CT). Diagnostic value of CT in conditions of pneumomediastinum and CT employing an "amplification" technique in dynamic CT-scanning (angio-CT) in combination with puncture tumour biopsy under CT control are discussed. CT was found to have certain advantages over other diagnostic techniques: simplicity, safety, the value of the information obtained, possible shortening of the diagnostic period.     

Host determinants of DNA alkylation and DNA repair activity in human colorectal tissue: O(6)-methylguanine levels are associated with GSTT1 genotype and O(6)-alkylguanine-DNA alkyltransferase activity with CYP2D6 genotype.

There is increasing evidence that alkylating agent exposure may increase large bowel cancer risk and factors which either alter such exposure or its effects may modify risk. Hence, in a cross-sectional study of 78 patients with colorectal disease, we have examined whether (i) metabolic genotypes (GSTT1, GSTM1, CYP2D6, CYP2E1) are associated with O(6)-methyldeoxyguanosine (O(6)-MedG) levels, O(6)-alkylguanine-DNA alkyltransferase (ATase) activity or K-ras mutations, and (ii) there was an association between ATase activity and O(6)-MedG levels. Patients with colon tumours and who were homozygous GSTT1(*)2 genotype carriers were more likely than patients who expressed GSTT1 to have their DNA alkylated (83 versus 32%, P=0.03) and to have higher O(6)-MedG levels (0.178+/-0.374 versus 0.016+/-0.023 micromol O(6)-MedG/mol dG, P=0.04) in normal, but not tumour, DNA. No such association was observed between the GSTT1 genotype and the frequency of DNA alkylation or O(6)-MedG levels in patients with benign colon disease or rectal tumours. Patients with colon tumours or benign colon disease who were CYP2D6-poor metabolisers had higher ATase activity in normal tissue than patients who were CYP2D6 extensive metabolisers or CYP2D6 heterozygotes. Patients with the CYP2E1 Dra cd genotype were less likely to have a K-ras mutation: of 55 patients with the wild-type CYP2E1 genotype (dd), 23 had K-ras mutations, whereas none of the 7 individuals with cd genotype had a K-ras mutation (P=0.04). No other associations were observed between GSTT1, GSTM1, CYP2D6 and CYP2E1 Pst genotypes and adduct levels, ATase activity or mutational status. O(6)-MedG levels were not associated with ATase activity in either normal or tumour tissue. However, in 15 patients for whom both normal and tumour DNA contained detectable O(6)-MedG levels, there was a strong positive association between the normal DNA/tumour DNA adduct ratio and the normal tissue/tumour tissue ATase ratio (r(2)=0.66, P=0.001). These results indicate that host factors can affect levels both of the biologically effective dose arising from methylating agent exposure and of a susceptibility factor, the DNA repair phenotype.     

Dual tumours in the GI tract: synchronous and metachronous stromal (GIST) and epithelial/neuroendocrine neoplasms

Gastrointestinal stromal tumours (GIST) constitute the most frequent group of mesenchymal tumours in the gastrointestinal tract (GI). During the last several decades major advances have been taken in the diagnostics, treatment, and understanding of its pathogenesis. However, much less is known about the either metachronous or synchronous concurrence of GIST and other tumours of different histogenesis. In the present study clinicopathological data of 43 patients with histologically proved gastrointestinal stromal tumour were studied mainly in regard of the occurrence of a secondary neoplasm. Among the 43, 7 cases were found with secondary tumour mainly of epithelial origin. In three cases (cases 3, 5, and 7) GIST concurred with colorectal adenocarcinoma, in one case (case 1) GIST occurred in a patient with a 3-years-history of chronic lymphocytic leukaemia (CLL), in other two (cases 2 and 4) the stromal tumour was combined with in situ adenocarcinoma of the stomach and carcinoid of the pancreas, respectively. In case 6, GIST concurred with a duodenal Brunner gland adenoma. In five cases the stromal tumour and the other neoplasm occurred synchronously, and in four of them, being the stromal tumour clinically silent, GISTs were intraoperative findings. This confirms the importance of surgical intraabdominal control before closure. In one hand the repeated concurrence of GIST and colorectal adenocarcinoma in our series, and on the other hand, that of GIST and adenocarcinoma of the stomach in the literature, may indicate an at least partly common factor, which may be involved in the pathogenesis of these neoplasms.     

Analysis of adrenocortical tumors morphology as regards their structure and potential malignancy

INTRODUCTION: A consequence of diagnosis of adrenocortical carcinoma (ACC) is introduction of pharmacological therapy, precise monitoring of the patients and in some cases re-operation. The aim of the study is to analyse morphology of adrenocortical tumours as regards their malignancy by use of criteria proposed by Weiss. MATERIAL AND METHODS: 110 adrenocortical tumours in 107 patients were analysed (M 27.1%, F 72.9%; age 32 to 77 years, mean 55.2 +/- 9.7). Conn syndrome was diagnosed in 16 patients (14.9%), Cushing syndrome in 12 (11.2%), and virilisation in 3 (2.8%). In 76 patients (71.0%) biochemical tests did not reveal hormonal hyperactivity of the tumour. RESULTS: In routine histopatological examination ACC was diagnosed in 6 tumours (5.4%), adrenocortical adenoma (ACA) in 92 (83.6%) and adrenocortical hyperplasia in 12 (10.9%). Nuclear grade III or IV was observed in 8 tumours (7.3%), mitotic rate > 5/50 high power fields in 6 (5.4%), atypical mitoses in 5 (4.5%), clear cells constituting < 25% of the tumour in 10 (9.1%), diffuse architecture in 8 (7.3%), necrosis in 16 (14.5%), veins infiltration in 4 (3.6%), sinusoids infiltration in 7 (6.3%), and tumour capsule infiltration in 5 (4.5%). Among ACC tumours 4-9 features of malignancy were present, among ACA--0-3 features. Statistical analysis revealed correlation between number of criteria proposed by Weiss and maximal tumour size (p < 0.05). CONCLUSION: The structure and cell arrangement in adrenocortical adenoma are heterogeneous. Application of criteria proposed by Weiss in histopathological examination of adrenocortical tumours can be useful in differentiating adrenocortical adenoma from carcinoma.