Malignant rhabdoid tumor of the kidney in a child: report of a case with recurrence in the contralateral kidney

BACKGROUND: Malignant rhabdoid tumor (MRT) of the kidney is a rare and aggressive neoplasm with a controversial histogenesis. Although their immunohistochemistry may be diverse, the rhabdoid phenotype and mutations of the INI1 gene are consistently exhibited by MRTs regardless of their location. CASE: MRT recurred in the contralateral kidney in a 12-month-old child within 6 months after the initial histologic diagnosis, nephrectomy and autologous stem cell transplant. The presence of widespread metastases at the time of the recurrence precluded any further chemical and surgical diagnostic or therapeutic intervention. CONCLUSION: To the best of our knowledge, only a few cases describing the cytologic diagnosis of MRT of the kidney in a child have been reported. This case illustrates the usefulness of cytologic diagnosis in an MRT recurrence.     

Expression of Cathepsin D and pS2 in imprint smears of breast carcinoma

athanassiadou p.p., athanassiades p. h., daffaris p., petrakakou e. i., fflerffa ch. i. and kffirkou k. a. (1998) Cytopathology 9, 240–247
Expression of Cathepsin D and pS2 in imprint smears of breast carcinoma
The aim of this study was to add to existing information on the effects of certain tumour markers expressed by breast cancers on tumour malignancy as evidenced by size of primary and occurrence of lymph node invasion. One hundred freshly resected breast cancers were examined by immunocytochemical staining of imprint smears for Cathepsin D and pS2. Oestrogen receptor (ER) and progesterone receptor (PR) were tested for by dextrose-coated charcoal (DCC) assay and the results correlated with tumour size, histology and presence or absence of lymph node metastases at the time of surgery using χ² analysis. A significant positive correlation was demonstrated between Cathepsin D positivity and ER, PR and pS2 positivity. In tumours < 2 cm in diameter at surgery a positive correlation was observed between Cathepsin D positivity and the presence of lymph node metastases. The findings support the hypothesis that Cathepsin D may promote early metastasis, possibly by its proteolytic activity.     

Clear cell sarcoma, cellular mesoblastic nephroma and metanephric adenoma: cytological features and differential diagnosis with Wilms tumour

Wilms' Tumour (WT) is the most common kidney tumour in childhood, this fact and the embryonic complexity of WT create, whenever one of its three classical components predominates in cytologic smears, difficulties in the differential diagnoses with other less common entities. In the present study, we review the cytological and immunohistochemical characteristics of three children renal tumours, a Clear Cell Sarcoma of the Kidney (CCSK-case1), a Cellular Mesoblastic Nephroma (CMN-case2) and a Metanephric Adenoma (MA-case3) and compare them, for differential diagnostic purposes, with smears of blastematous, mesenchymal and epithelial predominant WTs, previously diagnosed in our Department. In all cases a mass was detected in the abdomen (2 and 8 year old children-cases 1 and 3, respectively), and pre-birth in case 2 (the tumour was detected during pregnancy). Fine needle biopsy was performed followed by routine cytologic examination. The presence of moderate amount of blue pale cytoplasm in neoplastic cells (case1), the presence of tightly cohesive, bland, spindle tumour cells (case2) and the identification of small, well differentiated epithelial tubules with psammoma bodies in case 3, were the main morphologic characteristics that we think represent the most important elements for distinguishing our cases from a WT. Immunoreactivity was only helpful in case 1 as we found a characteristic dot-like pattern positivity for vimentin, in the absence of immunoreactivity for the other markers that are usually positive in WT. Summing up, these three cases demonstrate that cytopathologists should be aware of the occurrence of uncommon renal neoplasms in childhood and should be acquainted with their characteristics, in order to avoid false diagnoses.     

STIM1: a novel phosphoprotein located at the cell surface

STIM1 is a novel candidate growth suppressor gene mapping to the human chromosome region 11p15.5 that is associated with several malignancies. STIM1 overexpression studies in G401 rhabdoid tumour, rhabdomyosarcoma and rodent myoblast cell lines causes growth arrest, consistent with a potential role as a tumour growth suppressor. We used highly specific antibodies to show by immunofluorescence and cell surface biotinylation studies that STIM1 is located at the cell surface of K562 cells. Western blot analysis revealed that the 90-kDa STIM1 protein is ubiquitously expressed in various human primary cells and tumour cell lines. STIM1 is not secreted from cells and does not appear to undergo proteolytic processing. We show evidence of post-translational modification of STIM1, namely phosphorylation and N-linked glycosylation. Phosphorylation of STIM1 in vivo occurs predominantly on serine residues. Thus, STIM1, the putative tumour growth suppressor gene is ubiquitously expressed and has features of a regulatory cell-surface phosphoprotein.     

Novel role for insulin as an autocrine growth factor for malignant brain tumour cells

AT/RTs (atypical teratoid/rhabdoid tumours) of the CNS (central nervous system) are childhood malignancies associated with poor survival rates due to resistance to conventional treatments such as chemotherapy. We characterized a panel of human AT/RT and MRT (malignant rhabdoid tumour) cell lines for expression of RTKs (receptor tyrosine kinases) and their involvement in tumour growth and survival. When compared with normal brain tissue, AT/RT cell lines overexpressed the IR (insulin receptor) and the IGFIR (insulin-like growth factor-I receptor). Moreover, insulin was secreted by AT/RT cells grown in serum-free medium. Insulin potently activated Akt (also called protein kinase B) in AT/RT cells, as compared with other growth factors, such as epidermal growth factor. Pharmacological inhibitors, neutralizing antibodies, or RNAi (RNA interference) targeting the IR impaired the growth of AT/RT cell lines and induced apoptosis. Inhibitors of the PI3K (phosphoinositide 3-kinase)/Akt pathway also impaired basal and insulin-stimulated AT/RT cell proliferation. Experiments using RNAi and isoform-specific pharmacological inhibitors established a key role for the class I(A) PI3K p110alpha isoform in AT/RT cell growth and insulin signalling. Taken together, our results reveal a novel role for autocrine signalling by insulin and the IR in growth and survival of malignant human CNS tumour cells via the PI3K/Akt pathway.     

Chromosomal Abnormality T(9;22)(Q22;Q12) In an Extraskeletal Myxoid Chondrosarcoma Characterized By Fine Needle Aspiration Cytology, Electron Microscopy, Immunohistochemistry and Dna Flow Cytometry

A multidisciplinary approach was taken to characterize a soft tissue tumour. In smears prepared from aspirated material, uniform tumour cells, embedded in a myxoid matrix and partly arranged in a lace-like pattern, were found. Histopathology showed a lace-like pattern of cells in a matrix of hyaluronidase-stable mucins. Cytoplasmic positivity for S-100 protein was found in some tumour cells. Electron microscopic analysis revealed intracisternal aggregates of microtubules. All these features are consistent with the diagnosis of extraskeletal myxoid chondrosarcoma (EMC). DNA flow cytometry showed a diploid DNA content. Cytogenetic examination revealed the tumour karyotype 45, XY, t(2;11)(q31;p15), t(9;22)(q22.3;q12), dic(13;22)(p11;p13). Because similar 9;22-translocations have been described in two other cases of EMC, we conclude that t(9;22)(q22–31;q11–12) is a specific rearrangement in this tumour type. Cytogenetic analysis may thus be of diagnostic value in the examination of tumours with this and similar histologies.     

High-density single nucleotide polymorphism array analysis in patients with germline deletions of 22q11.2 and malignant rhabdoid tumor

Malignant rhabdoid tumors are highly aggressive neoplasms found primarily in infants and young children. The majority of rhabdoid tumors arise as a result of homozygous inactivating deletions or mutations of the INI1 gene located in chromosome band 22q11.2. Germline mutations of INI1 predispose to the development of rhabdoid tumors of the brain, kidney and extra-renal tissues, consistent with its function as a tumor suppressor gene. We now describe five patients with germline deletions in chromosome band 22q11.2 that included the INI1 gene locus, leading to the development of rhabdoid tumors. Two patients had phenotypic findings that were suggestive but not diagnostic for DiGeorge/Velocardiofacial syndrome (DGS/VCFS). The other three infants had highly aggressive disease with multiple tumors at the time of presentation. The extent of the deletions was determined by fluorescence in situ hybridization and high-density oligonucleotide based single nucleotide polymorphism arrays. The deletions in the two patients with features of DGS/VCFS were distal to the region typically deleted in patients with this genetic disorder. The three infants with multiple primary tumors had smaller but overlapping deletions, primarily involving INI1. The data suggest that the mechanisms underlying the deletions in these patients may be similar to those that lead to DGS/VCFS, as they also appear to be mediated by related, low copy repeats (LCRs) in 22q11.2. These are the first reported cases in which an association has been established between recurrent, interstitial deletions mediated by LCRs in 22q11.2 and a predisposition to cancer. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Telomerase activity levels in the surgical margin and tumour distant tissue of the squamous cell carcinoma of the head-and-neck.

The survival of patients with a head-and-neck squamous cell carcinoma is determined by loco-regional recurrence and second primary carcinomas. As a complement to histopathology, molecular changes of tumour marginal and tumour distant tissue may confirm curative surgical tumour extirpation. We tested telomerase activity with PCR-ELISA kits.20 tumour margin biopsies were chosen by the surgeon from 20 patients. In addition, 3 tissue samples were taken from each of 20 additional patients, one from the carcinoma centre, the tumour margin and one distant from the tumour. 50% of the carcinoma centres were telomerase-positive. Thirteen of the 40 tumour margin samples showed increased telomerase levels, and in 3 of these residual carcinoma was histopathologically detected. Six of the 20 tumour distant tissues revealed increased telomerase levels. Telomerase positivity in carcinoma-free tumour margins correlated with a good prognosis. Confirmation of the results in a larger patient group is needed.     

A non-functioning pancreatic neuroendocrine tumour: a case report

We present the diagnostic and therapeutic difficulties encountered in a patient with a clinically advanced pancreatic neuroendocrine tumour. The report concerns a 60-year-old female patient with the diagnosis of non-functioning pancreatic neuroendocrine tumour (NET G1) with liver, peripancreatic lymph node and mediastinal metastases. Due to the presence of advanced disease (inoperable pancreatic tumour, presence of multiple metastases) the patient was considered ineligible for surgical treatment on two occasions. Tissue samples for histopathology were collected during an exploratory laparotomy, which made it possible to establish the diagnosis. As somatostatin receptor scintigraphy was positive, the patient was started on somatostatin analogues and radionuclide therapy was initiated, resulting in satisfactory response in the form of complete remission of liver metastases and the decreased size of the primary tumour in the pancreas. The use of somatostatin analogues in the case of an inoperable neuroendocrine tumour which was assessed as clinically advanced, yet possessing a low proliferative potential, is a promising therapeutic option.     

Expression of cyclooxygenase-2 in invasive breast carcinomas and its prognostic impact

Representative tumour sections from 468 patients with invasive breast cancer were immunostained for cyclooxygenase-2 (COX-2) and evaluated. The relationships between COX-2 expression, clinical outcome and various clinicopathological variables, including tumour vascularity and disseminated tumour cells (DTC) in the bone marrow were examined. COX-2 expression in invasive breast carcinoma cells was positively associated with oestrogen receptor and/or progesterone receptor positivity (p<0.001). Triple-negative tumours showed no/low COX-2 expression more frequently than other tumour types (p<0.001). Expression of COX-2 was not associated with breast cancer-specific survival (p=0.49, log-rank) or distant disease-free survival (p=0.67, log-rank) for all patients, including lymph node-negative, untreated patients (p>0.14, log-rank). There was also no significant association between COX-2 expression and histological grade, tumour size, nodal status, DTC in bone marrow, p53, HER2, or tumour vascularity. In conclusion, COX-2 expression in this series was associated with the presence of hormone receptors. Low COX-2 expression was observed in triple-negative breast carcinomas.     

Immunohistochemical co-expression of c-erbb-2/Neu oncoprotein, altered tumour suppressor (p53) protein, EGF-R and EMA in histological subtypes of infiltrating duct carcinoma of the breast

Carcinoma of the breast has an unpredictable biological behaviour. Several oncogenes have been implicated in the progression of breast cancer. Immunohistochemical staining of c-erbB-2 (Neu) oncoprotein and mutant p53 protein on 45 cases of infiltrating duct carcinoma (IDC) of the breast revealed 33% membrane positivity of c-erbB-2 oncoprotein, 46% nuclear positivity of mutated p53 protein, 33% and 84% membrane positivity of EGF-R and EMA respectively. Staining profile of c-erb-B2 oncoprotein in various histological subtypes of IDC of the breast indicated a high positivity rate in comedo followed by NOS and cibriform subtype. Similarly, high incidence of immunopositivity of mutated p53 protein was observed in comedo and cibriform subtypes while papillary carcinoma were found exclusively positive for mutated p53 protein. Interestingly, tubular subtype of IDC was not positive for c-erbB-2 oncoprotein as well as p53 mutant protein. Further, comedo and cibriform subtypes of IDC revealed 'high grade' histological features of tumour of the breast with high mitotic count, presence of marked pleomorphism and multinucleation thus, reflecting a positive relationship with overexpression of c-erbB-2 (Neu) oncoprotein as well as mutant p53 protein. The results on immunoexpression of c-erbB-2 oncoprotein and mutated p53 protein in various histological subtypes of IDC of the breast demonstrated c-erbB-2 status as an important predictor and also indicated that oncogene product may be involved in growth factor response pathway.     

Immunocytochemical evaluation of proliferative activity in human brain tumours

The immunocytochemical expression of the antigen reacting with the monoclonal antibody Ki-67 (Ki-67 positivity) was investigated in 50 imprint preparations from human brain tumours. Data were related to tumour proliferative activity, as determined from in vivo bromodeoxyuridine (BrdU) incorporation (BrdU-labelling index, BrdU-LI) and histology. The percentage of Ki-67-positive cells was greater than the corresponding BrdU-LI value in all tumours, and the differences in Ki-67 positivity among tumour subtypes paralleled the BrdU-LI differences. Both the BrdU-LI and the percentage of Ki-67 positive cells were significantly greater (P less than 0.005) in the group of clinically aggressive adult tumours, histologically identified as anaplastic astrocytomas and glioblastomas, than in the less aggressive ones (oligodendroglioma, meningiomas, schwannomas, pituitary adenomas, dermoid cyst) and in the cerebral metastatic localizations. These data suggest that Ki-67 positivity, which is easily evaluated with immunocytochemistry, is related to the proliferative activity of brain tumours and that this parameter is endowed with clinical significance.     

Place de la TEP au FDG (18F) dans l’exploration des syndromes neurologiques paranéoplasiques

Paraneoplastic neurological syndromes (PNS) are rare non-metastatic manifestations of cancer. However, in this family of diseases, to recognize the underlying malignancy is an emergency. The ultimate aim is to treat the patient and try to stabilize or improve the neurological dysfunction, which is frequently the cause of the patient's death. The yield of FDG PET seems to be poor in unselected PNS. In the last decade, neurologists have attempted to provide more rigorous diagnostic criteria for PNS. Thus, “classical” PNS and a panel of “well-characterized” onconeural antibodies have been defined in order to facilitate triage of patients for whom FDG PET would be more sensitive. Currently, given the limited availability of PET cameras in France, this examination should be performed in the presence of either a “classical” PNS with or without onconeuralantibodies positivity or other PNS with onconeural antibodies positivity. The FDG PET should be triggered after a negative conventional imaging work up.     

The diagnostic performance of current tumour markers in surveillance for recurrent testicular cancer: A diagnostic test accuracy systematic review

In this diagnostic test accuracy systematic review we summarise the evidence on the diagnostic accuracy of blood α-fetoprotein (AFP), human chorionic gonadotropin (HCG) and lactate dehydrogenase (LDH) in surveillance for testicular cancer recurrence in adults. We searched four electronic databases for studies that reported the diagnostic accuracy of HCG, AFP, and/or LDH in sufficient detail for sensitivity and specificity to be calculated by extracting a 2 × 2 table comparing biomarker positivity with testicular cancer recurrence. Screening, data extraction and QUADAS-2 quality assessment were completed by two independent reviewers. From 2406 studies, nine met our inclusion criteria. Eight reported data at the per-patient level. Sample sizes were small (range 5 to 449 patients) and clinical heterogeneity precluded meta-analysis. In most studies the specificity for recurrence with AFP and HCG was high (90–100%) but sensitivity was often relatively low, suggesting that many recurrences would not be detected by tumour markers alone. The diagnostic performance of LDH appears poorer. Studies were methodologically weak, with probable selection, incorporation and partial verification bias, and many studies were excluded for not reporting on recurrence-free patients. Limitations including small sample sizes, high heterogeneity, and inconsistent and incomplete reporting mean these results must be interpreted with caution. Despite inclusion of biomarkers in international surveillance guidance, there remains a lack of high quality evidence about their accuracy, optimal thresholds, and the most effective surveillance strategy in relation to contemporary investigative modalities. Higher quality research using data from modern-day follow-up cohorts is necessary to identify opportunities to reduce unnecessary testing.     

Immunofluorescence assay for antinuclear factor: a nonspecific test in hospitalized medical patients.

Serum from 149 randomly selected hospitalized medical patients was tested for the presence of antinuclear factor (ANF) by the conventional immunofluorescence technique. Patients with positive and negative results were then compared as to clinical history, particularly previous drug exposure, physical findings, and levels of C-reactive protein and immune complexes in the serum. The frequency of ANF positivity was found to be very high (23%). Although the presence of ANF was significantly correlated (P less than 0.02) with a higher age, it was not significantly related to any other clinical or laboratory feature assessed. It was concluded that ANF testing cannot serve as a blind diagnostic screening tool for connective tissue diseases because of its nonspecificity.     

Detection of endometrial cancer by flow cytometry using two monoclonal antibodies.

BACKGROUND: To develop a supplementary diagnostic method for endometrial cancer by measuring the reactivity of various endometrial lesions with two monoclonal antibodies. METHODS: We investigated the reactivity of various endometrial lesions with two monoclonal antibodies (MSN-1 and MSN-3) by flow cytometry (one-color and two-color methods). RESULTS: The two-color method appeared to be suitable for use in place of simultaneous performance of the one-color methods with MSN-1 and MSN-3. The positivity rate for normal endometrium was 16.0% with the two-color method, which was lower than the rate of 30.0% obtained with concomitant used of the one-color methods. The positivity rate for endometrial cancer was high, 84.0%, with the two-color method. The positivity rate was 85.7% for well-differentiated endometrial cancer, 71.4% for moderately differentiated cancer, and 100.0% for poorly differentiated cancer; thus, the rate was high irrespective of the cellular differentiation. CONCLUSIONS: The two-color method is more useful than the one-color method as a supplementary diagnostic procedure for endometrial cancer.     

Metaplastic carcinomas of the breast—fine needle aspiration (FNA) cytology findings

nogueira m., andré s. and mendonça e. . (1998) Cytopathology 9, 291–300
Metaplastic carcinomas of the breast—fine needle aspiration (FNA) cytology findings
Metaplastic carcinomas of the breast are defined by mesenchymal and/or squamous cell components associated with ductal carcinoma and may raise diagnostic problems in FNA cytology. We reviewed FNA smears of a series of nine cases; seven were compared with histological sections and two with cell-block sections. The cytological pattern was diagnostic of carcinoma in six cases; in two cases a diagnosis of sarcoma/phyllodes tumour was considered, as cells were predominantly spindle-shaped. One case had a pleomorphic adenoma type pattern. The cytological findings suggesting a diagnosis of metaplastic carcinoma include a liquid aspirate, a proteinaceous or chondromyxoid background and a poorly differentiated tumour with multinucleated giant cells, neoplastic or histiocytic. A definite diagnosis requires the presence of both carcinomatous and metaplastic (squamous/mesenchymal) components.     

Improved radioimmunodetection of tumours using liposome-entrapped antibody

The discrimination of radioimmunodetection of tumours is reduced by the presence of circulating radiolabelled antibody (primary antibody). We have prepared liposomes containing an antibody to the primary antibody (secondary antibody), with the intention of complexing and delivering to the liver primary antibody which is not associated with the tumour. In mice bearing xenografts of human tumours which secrete the marker carcinoembryonic antigen (CEA), liposomally entrapped secondary antibody was able to reduce the blood levels of 125I-labelled anti-CEA within 2 h, without reducing the amount of anti-CEA bound to the tumour. We therefore suggest that the use of liposomally entrapped secondary antibody would improve the diagnostic potential of radioimmunodetection of tumours and their metastases.