Histologic transformation in marginal zone lymphomas†.

BACKGROUND: Histologic transformation (HT) is a poorly understood event in patients with marginal zone lymphoma (MZL). The aim of this study was to analyze incidence and risk factors for HT in a large series of MZL patients. PATIENTS AND METHODS: The studied cohort included 340 MZL patients diagnosed and treated between 1995 and 2012: 157 extranodal MZLs [mucosa-associated lymphoid tissue (MALT) lymphoma, 46%], 85 splenic MZLs (SMZLs, 25%) and 37 nodal MZLs (NMZLs, 11%). Sixty-one patients (18%) had bone marrow infiltration at presentation, with or without detectable involvement of peripheral blood, but without other involved sites; they were considered clonal B-cell lymphocytosis of marginal zone origin (CBL-MZ). RESULTS: With a median follow-up of 4.8 years, the median overall survival and progression-free survival of the whole population were 14.5 and 5 years, respectively. HT was observed in 13 cases [3.8%, 95% confidence interval (95% CI) 2%-6.5%]. Elevated lactate dehydrogenase (LDH) at diagnosis was associated with the risk of HT (P = 0.019). HT occurred in 5% of SMZLs, 4% of MALT lymphomas, 3% of NMZLs and 3% of CBL-MZ (P = 0.974). The risk of HT was 5% (95% CI 3-9%) at 5 and 10 years after diagnosis and 10% (95% CI 5%-20%) at 12 years. At the time of HT, most patients had high LDH and B symptoms. At a median follow-up of 12 months after HT, 4 of 13 patients died, all for lymphoma-related causes, with a 2-year post-transformation survival rate of 57% (95% CI 13%-86%). CONCLUSIONS: In this large retrospective series, the risk of HT across all MZL types appeared lower than the one reported for follicular lymphoma.

Laser capture microdissection is a valuable tool in the preoperative molecular screening of follicular lesions of the thyroid: an institutional experience.

OBJECTIVES: The application of molecular tests to thyroid fine needle aspiration (FNA) has been shown to be a valuable tool to better refine the pre-operative malignant risk of patients with indeterminate cytology results. In this study, we investigated the feasibility of using the laser capture microdissection (LCM) technique to obtain DNA and RNA for molecular tests in routine thyroid FNA smears. METHODS: Nine coupled FNA and histological retrospective cases and 31 prospective FNA cases with a follicular neoplasm/suspicious for a follicular neoplasm (FN/SFN) diagnosis were included in this study. Both cytological and histological specimens were investigated by direct sequencing and reverse transcription-polymerase chain reaction (RT-PCR) for BRAF and RAS mutations and for PAX8/PPARG and RET/PTC rearrangements, respectively. RESULTS: LCM yielded good DNA and RNA quality in all cases (100%) in both series, irrespective of the staining used (Giemsa, Papanicolaou, immunostain for thyroglobulin) and the cytology technique (conventional or liquid-based preparations). Total mutations found in the FNA and in the corresponding histological specimen in both series were: one PAX8/PPARG rearrangement in a follicular carcinoma (FC), four NRAS mutations [in two FCs, one papillary carcinoma and one follicular adenoma (FA)] and one HRAS mutation in one FA. The sensitivity was 67% and the specificity was 91%. CONCLUSIONS: LCM is a valuable tool to obtain good quality DNA and RNA for molecular tests in cytological material from thyroid FNA, and can be a useful option in the management of patients with an FN/SFN FNA diagnosis.

Generalized aggressive periodontitis in prepubertal age: description and comparison of two cases.

Aggressive periodontitis is a rare form of periodontal disease and it can involve both the deciduous dentition and the permanent one. It causes a rapid loss of periodontal attachment. The paper aims to describe two cases of severe generalized prepubertal periodontitis: the first child doesn't suffer from neither systemic diseases nor alteration of functionality of polymorphonuclear and periodontal disease involved both his deciduous dentition and the first permanent molars. The second child had a deficiency of functionality of polymorphonuclear but periodontal disease involved only primary dentition thanks to his immediate improvement of home dental hygiene. This comparison shows the importance of early diagnosis and especially of optimal dental oral hygiene. Infant healthcare professionals, as pediatric dentists and pediatricians, should have the necessary knowledge for early and correct diagnosis and clinical management of disease.

HER2 gene copy number status may influence clinical efficacy to anti-EGFR monoclonal antibodies in metastatic colorectal cancer patients.

BACKGROUND: In metastatic colorectal cancer (mCRC), KRAS is the only validated biomarker used to select patients for administration of epidermal growth factor receptor (EGFR)-targeted therapies. To identify additional predictive markers, we investigated the importance of HER2, the primary EGFR dimerisation partner, in this particular disease. METHODS: We evaluated the HER2 gene status by fluorescence in situ hybridisation (FISH) in 170 KRAS wild-type mCRC patients treated with cetuximab or panitumumab. RESULTS: Depending on HER2 gene copy number status, patients showed three distinct cytogenetic profiles: 4% of patients had HER2 gene amplification (R:HER2/CEP17 ≥ 2) in all neoplastic cells (HER2-all-A), 61% of patients had HER2 gain due to polysomy or to gene amplification in minor clones (HER2-FISH+*), and 35% of patients had no or slight HER2 gain (HER2-FISH-). These subgroups were significantly correlated with different clinical behaviours, in terms of response rate (RR; P=0.0006), progression-free survival (PFS; P<0.0001) and overall survival (OS; P<0.0001). Patients with HER2-all-A profile experienced the worst outcome, patients with HER2-FISH- profile showed an intermediate behaviour and patients with HER2-FISH+* profile were related to the highest survival probability (median PFS in months: 2.5 vs 3.9 vs 7.6, respectively; median OS in months: 4.2 vs 9.7 vs 13, respectively). CONCLUSION: HER2 gene copy number status may influence the clinical response to anti-EGFR-targeted therapy in mCRC patients.

Tumefactive demyelinating lesions during etanercept treatment requiring decompressive hemicraniectomy.

Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory and immunoregulatory cytokine involved in the pathogenesis of several autoimmune disorders. Etanercept, a TNF-α antagonist (anti-TNF-α) acting as a soluble TNF-α receptor, has been associated with neurological demyelinating disorders. This paper aims to report an unusual case showing tumefactive central nervous system (CNS) inflammatory demyelination in a patient in the course of TNF -α antagonist therapy, requiring decompressive hemicraniectomy. This report is based on magnetic resonance imaging (MRI) findings and histology. A biopsy confirmed the inflammatory demyelinating nature of the lesions. The clinical presentation is unusual due to the severity of the disease process, requiring decompressive hemicraniotomy with a clinically favorable outcome.

The impact of the introduction of total mesorectal excision on local recurrence rate and survival in rectal cancer: long-term results.

PURPOSE: To investigate the influence of the introduction of total mesorectal excision (TME) on local recurrence rate and survival in patients with rectal cancer. METHODS: A total of 171 consecutive patients underwent anterior or abdominoperineal resection for primary rectal cancer. When the TME technique was introduced, the clinical setting, including the surgeons, remained the same. Group 1 (1993-95, n =53) underwent conventional surgery and group 2 (1995-2001, n = 118) underwent TME. All patients were followed for 7 years or until death. RESULTS: Between the two groups, no statistically significant differences were present with regards to patient-, treatment-, or tumor-related characteristics apart from the time point of radiotherapy. The total local recurrence rates were 11 of 53 (20.8%) in group 1 and 7 of 118 (5.9%) in group 2, and the rates of isolated local recurrences were 6 of 53 (11.3%) in group 1 and 2 of 118 (1.7%) in group 2. Both differences were highly statistically significant. The disease-free survival in groups 1 and 2 was 60.4 and 65.3% at 5 years, and 58.5 and 65.3% at 7 years, respectively. Excluding patients with synchronous or metachronous distant metastasis from the analysis, both the disease-free survival and the cancer-specific survival were statistically significantly better in group 2 than in group 1. No statistically significant difference between the two groups was detected regarding the overall survival. CONCLUSIONS: The introduction of TME led to an impressive reduction of the local recurrence rate. Survival is mainly determined by the occurrence of distant metastasis, but TME seems to improve survival in patients without systemic disease.

Prognostic and predictive value of TOPK stratified by KRAS and BRAF gene alterations in sporadic, hereditary and metastatic colorectal cancer patients.

BACKGROUND: Our aim was to investigate the prognostic and predictive value of the oncogenic MAPKK-like protein T-cell-originated protein kinase (TOPK) stratified by KRAS and BRAF mutations in patients with sporadic, hereditary and metastatic colorectal cancer (CRC) treated with anti-EGFR therapy. METHODS: Immunohistochemistry (IHC) for TOPK was performed on four study groups. Group 1 included two subgroups of 543 and 501 sporadic CRC patients used to test the reliability of TOPK expression by IHC. In Group 2, representing an additional 222 sporadic CRCs, the prognostic effect of TOPK stratified by KRAS and BRAF was assessed. The prognostic effect of TOPK was further analysed in Group 3, representing 71 hereditary Lynch syndrome-associated CRC patients. In Group 4, the predictive and prognostic value of TOPK was analysed on 45 metastatic patients treated with cetuximab or panitumumab stratified by KRAS and BRAF gene status. RESULTS: In both sporadic CRC subgroups (Group 1), associations of diffuse TOPK expression with clinicopathological features were reproducible. Molecular analysis of sporadic CRCs in Group 2 showed that diffuse TOPK expression was associated with KRAS and BRAF mutations (p<0.001) and with poor outcome in patients with either mutation in univariate and multivariate analysis (P=0.017). In hereditary patients (Group 3), diffuse TOPK was linked to advanced pT stage. In metastatic patients treated with anti-EGFR therapy (Group 4), diffuse TOPK expression was linked to dismal outcome despite objective response to treatment (P=0.01). CONCLUSIONS: TOPK expression is an unfavourable prognostic indicator in sporadic patients with KRAS or BRAF mutations and also in patients with metastatic disease experiencing a response to anti-EGFR therapies. The inhibition of TOPK, which could benefit 30-40% of CRC patients, may represent a new avenue of investigation for targeted therapy.

Assessment of breast cancer opportunistic screening by clinical-pathological indicators: a population-based study.

BACKGROUND: Although some clinical-pathological features of breast cancers, such as the incidence of ductal cancer in situ (DCIS) and the diameter of invasive tumours, are sensitive indicators of early detection, comprehensive population-based studies of opportunistic screening are needed. METHODS: Cases of DCIS or invasive breast cancer diagnosed in 1996-2007 were identified from the Ticino Cancer Registry (south of Switzerland). Time trends of age-adjusted incidence and mortality, as well as main clinical-pathological features, such as tumour diameter, AJCC stage and histological grade, were analysed. RESULTS: A total of 3047 incident cases of female breast cancer were identified. The proportion of DCIS with respect to invasive cases increased from 5.8% in the period 1996-2001 to 6.4% in the period 2002-2007. The median tumour size of invasive cancers decreased from 20 mm in 1996-2001 to 18 mm in 2002-2007 (P<0.0001). An increase in well/moderately differentiated invasive tumours, from 67% in the period 1996-2001 to 73% in 2002-2007 (P<0.001), was detected and resulted in an Annual Percentage Change of incidence of 2.8 (95% confidence interval: 1.3; 4.3). CONCLUSION: An opportunistic screening strategy can lead to an improvement of prognostic features at diagnosis, but these features are still less favourable than those achieved by organised screening programmes.

Differing deregulation of EGFR and downstream proteins in primary colorectal cancer and related metastatic sites may be clinically relevant.

Cetuximab and panitumumab efficacy in metastatic colorectal cancer (mCRC) may be influenced by EGFR gene status and/or deregulation of its downstream signalling proteins detected in primary tumour. However, metastasis might have different molecular patterns with respect to primary tumour, possibly affecting the prediction of EGFR-targeted therapy efficacy. We analysed primary tumour and metastasis in 38 mCRC patients. Twelve cases were cetuximab/panitumumab treated. EGFR gene status and protein expression were investigated through fluorescent in situ hybridisation and immunohistochemistry (IHC), K-Ras/BRAF mutations by sequencing and PTEN expression by IHC. We observed EGFR gene deregulation in 25 out of 36 primary tumours and 29 out of 36 metastases, K-Ras mutations in 16 out of 37 cancers and in 15 out of 37 metastases, BRAF mutations in 2 out of 36 cancers and 2 out of 36 metastases and PTEN loss in 8 out of 38 cancers and 12 out of 38 metastases. For the first time in literature, we show that primary colorectal cancer and paired metastasis may exhibit difference with respect to EGFR pathway deregulation mechanisms possibly implying a different response to cetuximab or panitumumab treatment. The investigation of treated patients confirms this hypothesis. We therefore suggest that the analysis of metastatic lesion should be considered in patient management as well as in designing future clinical trials aimed to investigate the effect of anti-EGFR monoclonal antibodies in the treatment of mCRC.

Breast cancer classification according to immunohistochemical markers: clinicopathologic features and short-term survival analysis in a population-based study from the South of Switzerland.

BACKGROUND: Breast cancer may be classified into distinct molecular subtypes based on gene expression profiling and/or immunophenotypic characteristics. Aim of the study was to investigate prevalence, clinicopathologic features and overall survival (OS) of molecular subtypes, in a large European population-based study. PATIENTS AND METHODS: All invasive breast cancers from 2003 to 2007 were selected from the files of Ticino Cancer Registry. Molecular subtypes were defined by immunohistochemical markers. Clinicopathological characteristics and short-term OS were analyzed. RESULTS: Of 1214 invasive breast cancers, 73.2% were luminal A subtype, 13.8% luminal B, 7.4% basal like and 5.6% Her2/neu. Basal like presented largely in premenopausal women and displayed aggressive features, such as large tumor size, poorly differentiated cancers, high Ki-67 proliferation index and the worst 24-month OS. Luminal A included the highest percentage of patients >70, the highest proportion of stage I tumors and well/moderately differentiated lesions. Her2/neu was more frequent in postmenopausal women and showed the highest percentage of positive lymph nodes and stage IV cases. CONCLUSION: This is a comprehensive European population-based study on breast cancer molecular subtypes. We provide strong evidence that the molecular classification is useful for clinical management and superior to World Health Organization classification in terms of short-term prognostic value.

Long-term outcome following Helicobacter pylori eradication in a retrospective study of 105 patients with localized gastric marginal zone B-cell lymphoma of MALT type.

BACKGROUND: Treatment aimed at eradicating Helicobacter pylori infection results in lymphoma remission in most localized gastric mucosa-associated lymphoid tissue (MALT) lymphomas. The aim of this survey is to investigate the long-term effect of this therapeutic approach in a large series of patients. METHODS: One hundred and five patients with localized gastric MALT lymphoma were initially treated only with H. pylori eradication regimens. Lymphoma responses were graded using the Wotherspoon score. RESULTS: Helicobacter pylori, detected by histology in 81% of cases, was eradicated in all positive patients. Histological regression of the lymphoma was achieved in 78 of 102 assessable patients [76%, 95% confidence interval (CI): 67% to 84%] with complete remission (score 0-2) in 66 and partial remission (score 3) in 12. At a median follow-up time of 6.3 years, histological remission was consistently confirmed in 33 of 74 assessable patients, while 25 had score fluctuations (from 0 to 4) and 13 presented a lymphoma relapse (score 5). Only one patient had a distant progression. Transformation to a large-cell lymphoma was seen in two cases. The 5- and 10-year overall survival is 92% (95% CI: 84% to 96%) and 83% (95% CI: 70% to 91%), respectively. Only one patient died of lymphoma after transformation to a high-grade lymphoma. CONCLUSIONS: Helicobacter pylori eradication resulted in complete lymphoma remission in the majority of cases. Long-term clinical disease control was achieved in most patients. A watch and wait policy appears to be safe in patients with minimal residual disease or histological-only local relapse.

Human T cell development and HIV infection in human hemato-lymphoid system mice.

Advances in generation of mice that on human hematopoietic stem and progenitor cell transplantation develop and maintain human hemato-lymphoid cells have fueled an already thriving field of research. We focus here on human T cell development and HIV infection in Rag2 -/- gamma(c) -/- mice transplanted as newborns with human CD34+ cord blood hematopoietic stem and progenitor cells.

Oral health problems and needs in nursing home residents in Northern Italy.

OBJECTIVE: To describe the oral health status and treatment needs of a sample of elderly people residing in nursing homes in Northern Italy. RESEARCH DESIGN: a sample of 595 elderly residents (mean age 83.2+/-9.2 yrs), with adequate cognitive skills were examined by six calibrated dentists. RESULTS: The sample (82% women) was divided into two groups: edentulous (43%) and dentate. In the edentulous group 58% wore dentures in both jaws, 8% in only one jaw and 34% had no dentures. The main problems were dirty or loose dentures and poor oral hygiene. In the dentate group the mean number of teeth was 8.4+/-7.4, 53% wore dentures (removable, fixed or a combination). Poor oral hygiene was found in 86%, root caries in 51% and coronal caries in 46%. Their main needs were professional cleaning (72%), oral hygiene instructions (62%) and tooth/root extractions (56%). While normative needs were noted for 82% of the whole sample, oral treatment needs were accurately perceived by only 20% of residents, poorly by 24%, while 46% indicated that they had no oral treatment needs.

BCA-1 is highly expressed in Helicobacter pylori-induced mucosa-associated lymphoid tissue and gastric lymphoma.

Infection with Helicobacter pylori (Hp) induces the formation of lymphoid tissue in the stomach and the occasional development of primary gastric B-cell lymphomas. We have studied the expression of 2 chemokines that attract B lymphocytes, BCA-1 and SLC, in gastric tissue samples obtained from patients with chronic gastritis induced by Hp infection or nonsteroidal anti-inflammatory drugs, as well as from patients with Hp-associated low-grade and high-grade gastric lymphomas. High-level expression of BCA-1 and its receptor, CXCR5, was observed in all mucosal lymphoid aggregates and in the mantle zone of all secondary lymphoid follicles in Hp-induced gastric mucosa-associated lymphoid tissue (MALT). Follicular dendritic cells and B lymphocytes are possible sources of BCA-1, which is not expressed by T lymphocytes, macrophages, or CD1a(+) dendritic cells. Strong expression of BCA-1 and CXCR5 was also detected in the transformed B cells of gastric MALT lymphomas. By contrast, SLC was confined almost exclusively to endothelial cells in and outside the lymphoid tissue. Only scant, occasional SLC expression was observed in the marginal zone of MALT follicles. Our findings indicate that BCA-1, which functions as a homing chemokine in normal lymphoid tissue, is induced in chronic Hp gastritis and is involved in the formation of lymphoid follicles and gastric lymphomas of the MALT type.

Differentiated thyroid carcinoma in children and adolescents: a 37-year experience in 85 patients.

UNLABELLED: This study reports on 85 differentiated thyroid carcinoma (DTC) (72 papillary, 13 follicular) patients, younger than 18 yr of age at the time of diagnosis, consecutively treated during the period 1958-1995. METHODS: Follow-up (median: 111 mo, range 1-324 mo) consisted of clinical examination, serum thyroglobulin (Tg), 131I whole-body scintigraphy (whole-body scan) and other imaging procedures. RESULTS: Forty-six patients had undergone total thyroidectomy, 38 partial thyroidectomy and 1 thyroid biopsy. In 47 patients, lymph-adenectomy was also performed. Five patients were treated after surgery by external radiotherapy, 59 by 131I therapy and 16 by both modalities. Iodine-131 therapy was successful in ablating thyroid remnants in 35/48 cases, lymph node metastases in 8/11 cases and lung metastases in 12/16 cases. Among the patients with scintigraphic-confirmed disappearance of lung metastases, serum Tg was still detectable in 10 cases, but continued to decrease spontaneously even without further therapeutic doses of 131I. All patients were still alive after a median period of 137 mo (range 5-444 mo). Six patients experienced a recurrence of the disease in the neck. Sixty-seven patients were free of disease, 3 had lymph node metastases, 4 lung metastases and 11 had detectable levels of Tg without demonstrable metastases. No impairment of female fertility or untoward genetic effects were noticed. One male patient, treated with 3.33 GBq of 131I, was infertile due to oligospermia. One case of gastric cancer and one of breast cancer occurred 8 and 19 yr, respectively, after 131I therapy. CONCLUSION: Iodine-131 therapy is highly effective in reducing lung metastases, but undetectable levels of Tg are seldom achieved. Total thyroidectomy and 131I therapy is an effective and safe treatment for the majority of patients with DTC diagnosed in childhood or adolescence.

Assessment of female fertility and carcinogenesis after iodine-131 therapy for differentiated thyroid carcinoma.

UNLABELLED: The aim of this study was to evaluate female fertility, carcinogenic, and genetic effects after treatment with 131I of differentiated thyroid carcinoma. METHODS: A total of 814 females of child-bearing age were studied. The fertility of 627 females who received 131I therapy was compared to 187 untreated females. Birth histories of the children born from these women were registered. The carcinogenic effect was evaluated by comparing the incidence of tumors in 730 patients treated with 131I with an internal control group, as well as with local population incidence. RESULTS: There was no significant difference in the fertility rate, birth weight and prematurity between the two groups. Only one case of a ventricular septal defect was observed in a child born to a women treated with 131I. The overall standardized incidence ratio (SIR) of second tumors was 1.19 (95% CI: 0.76-1.77) in patients treated with 131I. An elevated SIR was registered for salivary gland tumors and melanoma. No case of leukemia was registered. CONCLUSION: The risk of long-term effects of 131I treatment of differentiated thyroid carcinoma is quite low. Iodine-131 may be safely used in treating cases with a high risk of recurrence.

Interphase cytogenetics in oncocytic adenomas and carcinomas of the thyroid gland.

Follicular neoplasms of oncocytic type in the thyroid gland frequently cause diagnostic problems and prognostic uncertainties. To identify numerical chromosomal aberrations of possible pathogenetic importance, we determined chromosome copy numbers in situ in interphase nuclei of 31 oncocytic adenomas and 25 oncocytic carcinomas. Archival formaldehyde-fixed, paraffin-embedded tumor samples and normal control thyroid tissues were arranged in arrays and analyzed by fluorescence in situ hybridization (FISH). We used pericentromeric or locus specific probes for chromosomes 1, 7, 8, 9, 11, 12, 17, 18, 22, and X as well as for the oncogenes Her2/neu, cyclin D1, N-myc, and c-myc. The average number of aneusomies per nucleus was significantly higher in carcinomas than in adenomas, and in both, monosomies were more frequent than polysomies. Loss of chromosome 22 was found in 8 of 21 (38%) carcinomas; in 5 cases, it was associated with chromosome 2 monosomy. Conversely, chromosome 2 aberrations were not found in adenomas. Monosomies for chromosome 8 and X were detected in most adenomas and carcinomas. The most common gains in adenomas and carcinomas were for chromosome 7 (13.8% and 32.0% of the cases, respectively), chromosome 12 (9.6% and 12.0%), and chromosome 17 (19.3% and 32.0%). None of the adenomas with trisomy 17 was associated with gains for chromosomes 7 and 12. None of the analyzed oncogenes was found to be amplified by FISH analysis. Our results indicate that numerical chromosomal aberrations in oncocytic follicular tumors of the thyroid gland are common findings and suggest that different patterns of aberrations may occur in these neoplasms.

Oncocytic (Hürthle cell) tumors of the thyroid: distinct growth patterns comparedwith clinicopathological features.

Neoplastic growth results from cell production that exceeds cell loss. We registered mitotic and apoptotic indices (MI and AI) in 97 immunohistochemically verified oncocytic (Hürthle cell) tumors of the thyroid (OT; 50 adenomas [OA], 20 atypical adenomas [aOA], and 27 carcinomas [OC]) and compared these kinetic data with histological diagnoses and other parameters. MI, although very low in all, was significantly higher in carcinomas than in adenomas. Conversely, AI did not differ as much among the 3 groups. This indicates that the magnitude of cell deletion did not play a prominent role in determining the disparate growth of the 3 types of oncocytic tumors. Cluster analysis with MI and AI per case as variables revealed the existence of 3 groups of neoplasms with highly distinct growth characteristics: (1) near-steady state (n = 78, all diagnostic categories represented); (2) progressive (n = 9, mostly carcinomas); and (3) regressive (n = 10, mostly adenomas). MI distinguished between histologically benign and malignant with the greatest discriminant power of the variables tested. Proliferative indices should thus be included in the differential diagnostic evaluation of oncocytic thyroid tumors. Our study also suggests that invasiveness and growth are 2 diverging properties of carcinomas.

Cytomegalovirus and kidney.

This study was conceived to identify specific morphological characteristics associated with cytomegalovirus (CMV) infection of the kidney. 33 patients with manifest CMV infection at autopsy and 32 biopsies of kidney transplants with active or inactive CMV infection were studied. In 8 patients of the autopsy group a CMV infection of the kidney was detected (CMV cells in 3 cases, positive viral tissue culture in 4 cases, positive in-situ hybridization in one case), which was associated with severe dissemination into different organs. In situ hybridization was not superior to ordinary light microscopy in the detection of CMV cells. The biopsies were screened for the presence of glomerulopathy. No association of glomerulopathy with CMV could be found by light microscopy, whereas a significant correlation of glomerulopathy with vascular rejection was demonstrated. No differences as to the incidence of glomerulopathy were found, when non-transplant patients with manifest CMV infection at autopsy were compared with matched controls. With active infection electron microscopy revealed no osmiophilic deposits, but in immunofluorescence tiny IgG deposits were identified within the glomeruli (p less than 0.01). IgM or C3 deposition in the glomeruli was not specifically associated with either CMV infection or vascular rejection. Thus morphological identification of CMV infection of the kidney is difficult, necessitating the detection of CMV cells, positive viral tissue culture or positive in-situ hybridization. Glomerulopathy in light microscopy is associated with vascular rejection and is therefore termed transplant glomerulitis. Tiny IgG deposits may be indicative of CMV infection, although these are not always present.