The Simpson-Golabi-Behmel syndrome: A clinical case and a detective story.

The Simpson-Golabi-Behmel syndrome (SGBS) is an overgrowth condition comprising "coarseness" of facial traits, supernumerary nipples, congenital heart defects, polydactyly and fingernail hypoplasia, and an increased risk of neonatal death and later neoplasia. Psychomotor development is usually normal. The syndrome is caused by mutation/deletion of the X-linked gene GPC3. We describe a new case of SGBS, that led to the discovery of an extended family segregating a GPC3 mutation and, ultimately, of an affected relative forgotten, but not lost, in an anatomical museum, where he was classified as a macrosomic newborn, who was born probably around 1940 and died neonatally of unknown cause. This baby boy becomes the oldest case of SGBS on record.

Clinical management and molecular cytogenetic characterization in a 45,X/46,X,idic(Yp) patient with severe hypospadia.

Cryptorchidism and proximal hypospadia in a newborn are highly suspicious for an intersex disorder, and proper investigations should be planned immediately after birth. In some hypospadic patients, the presence of a palpable gonad in the scrotum may induce to assign the male sex, whereas the anatomy of internal and external genitalia could be extremely complex, requiring an accurate evaluation before any definitive attribution of gender. The authors present a case of an infant, referred to the hospital for surgical treatment of a proximal hypospadia, who showed ambiguous external genitalia, absence of the right gonad, a partially dysgenetic left testis, and presence of both müllerian and wolffian structures. Cytogenetic analysis detected a mosaicism with a cell line showing an isodicentric Yp chromosome and a second one, a 45, X chromosomal complement. Because the baby had been assigned previously to male gender, he underwent a staged masculinizing correction of the genital anomalies. The authors discuss the necessity of a careful evaluation of these patients at birth by a multispecialistic team, for appropriate sex assignment and for the assessment of the risk of neoplastic degeneration.

[Bone marrow changes in HIV-positive patients (clinical, cytological, histological, and ultrastructural study of 57 cases)]. / Alterazioni osteomidollari in pazienti HIV positivi (studio clinico, citologico, istologico ed ultrastrutturale su 57 casi).

The authors take into consideration clinical, cytological, histological and ultrastructural pattern of 57 HIV+ patients. They want to quantify bone marrow alterations and research their relation with haematological pattern of these patients. They think that peripheral haematological deficit is related with cellular and stromal alterations of the bone marrow. In fact there are many morphological cellular alterations. The most characteristic are that of megakaryocytes. The alterations of these cells are, probably, responsible for bone marrow early sclerosis of these patients. The plasma cells are also numerous and activated. They respect an immunological response.

Cellular heterogeneity of DNA/total-protein content in human lung tumors, as determined by flow cytometry.

With the aim of distinguishing neoplastic cell sub-populations of different prognostic and diagnostic significance, dual-parameter measurements (DNA/protein) have been simultaneously determined in a (256, 256) channel matrix in lung samples derived from 110 patients affected by neoplastic and non-neoplastic lung diseases. Biparametric analysis demonstrated that cells with abnormally high red fluorescence (i.e., protein content), which is indicative of unbalanced growth, were often observed in malignant tumors as compared with normal lung samples. Furthermore, the dual-parameter analysis allowed recognition of additional aneuploid tumor-cell lines, indicating that the frequency of cytometrically determined diploid tumor is lower than that previously described by DNA monoparametric analysis. The recognition of aneuploid subpopulations by dual-parameter analysis in clinically and histologically negative one-parameter flow-cytometric "diploid" samples assumes important diagnostic value. The results have also shown the presence of multiple protein sub-populations in clones with the same ploidy value, indicating a higher level of cellular heterogeneity than demonstrated by DNA monoparametric measurements.

Cytokinetic investigation of lung tumors using the anti-bromodeoxyuridine (BUdR) monoclonal antibody method: comparison with DNA flow cytometric data.

In order to investigate the cytokinetics of malignant tumors and non-malignant lesions of the lung, tissue samples from 57 patients affected by non-small-cell carcinoma (NSCLC), small-cell carcinoma (SCLC), and benign and inflammatory lesions have been analyzed using the BUdR monoclonal antibody (MAb) method. This method is based on the preparation, at the time of surgery, of viable monocellular suspensions (using collagenase and DNase treatment) and the concomitant administration of BudR. The percentage of BudR-labelled cells was monitored by fluorescent microscopy using an FITC-labelled second antibody. In NSCLC, each histological group showed a wide range of labelling index (LI) values. On the contrary, SCLC exhibited a more homogeneous kinetic behaviour as evidenced by a narrowly distributed, higher LI. Tumors shown to be diploid by flow cytometry did not show a lower LI than aneuploid tumors. Furthermore, differences were constantly observed between the S-phase percent calculated using BUdR and that calculated using the DNA flow cytometric (FC) histogram, the latter always showing higher S-phase values. In an attempt to study the intra-tumor proliferative heterogeneity, multiple-site sampling was performed. Proliferative heterogeneity seemed to be higher inter-tumor than intra-tumor. Finally, a positive correlation (p less than 0.05) was found between LI and the actual doubling time (DT) of the primary tumor mass, evaluated using sequential radiographs. In conclusion, the present BUdR method can be considered a useful source of relevant information on in vivo cell growth, in parallel to other clinical (DT) and biological (DNA content) approaches.

DNA flow cytometric studies of 66 human lung tumors analyzed before treatment. Prognostic implications.

To investigate the prognostic implications of DNA flow cytometry in human lung tumors, we analyzed specimens from patients with neoplastic and non-neoplastic lung disease. Most non-neoplastic and normal (taken at the resection border) lung samples yielded a single cell population with diploid DNA content (only two normal lung specimens from two cancer patients had aneuploid DNA content). At least one aneuploid cell subpopulation was seen in 91 percent of NSCLC and 50 percent on SCLC. To show intratumor heterogeneity, multiple-site sampling was done whenever possible in both primary tumor and metastatic sites, revealing a high incidence of multiclonality (50 percent). Although diploid tumors were rare, they associated with a higher survival rate than aneuploid monoclonal and multiclonal tumors with hypoploid and/or hypertetraploid clones, which had the lowest survival. Cellular DNA content analysis in patients with lung tumors may be useful in prognostic evaluation.

Establishment of cell lines from serial samples from two patients with lung tumours before and after chemotherapy.

Six cell lines were derived from pleural effusions of two lung cancer patients and established in vitro in our laboratory. Cell line AE1 was obtained from a small cell lung cancer (SCLC) before the patient had received any chemotherapy; the other lines (AE2 and AE3) were established from tumour recurrences in the same patient after therapy. Cell lines DG1 and DG2 were derived from specimens of an untreated non-small cell lung cancer (NSCLC), while cell line DG3 originated from pleural effusions recurring in the same patient after therapy. The results of the present study show that: (a) the SCLC lines AE1, AE2 and AE3 are heterogeneous in their biological characteristics and in their chemosensitivity patterns. In particular lines AE2 and AE3 are less responsive to cis-Platinum (DDP) and Adriamycin (ADM) than line AE1, so that they may reflect resistant subpopulations existing within the original tumour, selected following therapy with these drugs. In contrast, however, line AE1 proved more resistant to Vepesid (VP16) than lines AE2 and AE3. (b) The three NSCLC lines are similar in various biological features as well as in their chemosensitivity to DDP and Vinblastine (VBL).

Results of surgical treatment for small cell carcinoma of the lung.

The records of 288 patients treated for small cell carcinomas of the lung are reviewed. Resectional surgery was performed in 150 cases (147 apparently curative and 3 palliative procedures), 73 patients were submitted to exploratory thoracotomy and 65 were deemed unsuitable for surgical treatment. Overall postoperative mortality after resection was 14,6% and 5-year survival rate 20,7%. Long term prognosis was significantly correlated to p-TNM (p less than 0,002) and host's immune response as evidenced by circulating peripheral lymphocytes/cumm (p less than 0,003), primary tumor lymphocytic infiltration (L.I.) (p less than 0.03), regional lymph-node reactivity (P.C.A., S.H. and C.A. development) (p less than 0,0001). Patients treated for Stage I disease and showing enhanced immune reactivity had a significantly better long term prognosis than Stage II, III and non reactive patients. Oat cell subtype had worse 5-year survival rates (10,7%) than intermediate cell subtype (25,4%), this difference however is devoid of statistical significance (p: not significant).