Carlo D. Baroni

Anaplastic large cell lymphoma (CD30+/Ki-1+): results of a prospective clinico-pathological study of 69 cases

Summary. Sixty‐nine anaplastic large cell lymphomas (ALCLs) were selected from an Italian comparative trial on MACOP‐B and F‐MACHOP. As no significant difference in effectiveness of the protocols emerged, they were considered homogenously treated. The ALCLs were divided into two groups according to previously defined criteria: 41 were common type (ALCLs‐CT) and 28 Hodgkin‐related (ALCLs‐HR). T‐cell phenotype was most common (58%), while B‐cell, null and hybrid forms accounted for 27%, 13% and 2%. Clinically, ALCLs CT and HR differed as to mean age (27 v 34·3 years) and presentation; all ALCLs‐HR showed mediastinal involvement, with bulky disease in 57%, and more frequent occurrence in stage II. In contrast, ALCLs‐CT showed mediastinal masses in 58·5%, infrequently revealed bulky disease (24%), and were not specifically associated to stage. Among the ALCLs‐CT, 68·4% achieved complete remission (CR), 24·4% partial remission (PR), one (2·4%) was resistant to therapy, and two (4·8%) had fatal drug toxicity. Of the ALCLs‐HR, 67·8% reached CR, 14·3% PR, and 17·9% did not respond. In CR, ALCLs‐CT showed a greater tendency to relapse (32·1%v 14·2%). At present, 65·8% of ALCLs‐CT and 67·8% of ALCLs‐HR are alive with overall survival/disease‐free survival averages of 31/27 and 29/24 months respectively. Our data emphasize that, independently of subtype, ALCLs benefit from the application of third‐generation protocols for high‐grade non‐Hodgkins lymphomas.

Presence and cellular distribution of HIV in the testes of seropositive subjects: an evaluation by in situ PCR hybridization

Cellular distribution of HIV‐1 proviral DNA has been studied, by in situ PCR hybridization, in the testes of infected men who died at various stages of the disease. In seropositive asymptomatic subjects, HIV‐1 proviral DNA was present in the nuclei of germ cells at all stages of their differentiation. The presence of provirus did not induce germ cell damage, was associated with normal spermatogenesis, and was not accompanied by morphologic signs of immune response. The observed HIV hybridization pattern of germ cells suggests clonal infection. Mechanisms responsible for HIV penetration in testicular germ cells remain to be clarified; however, the possibility of a direct infection of the germ cells by cell‐free virus is suggested. In the testes of AIDS‐deceased men, histologic features of hypoplasia with arrested spermatogenesis were evident, and few infected spermatogonia and spermatocytes were observed. The whole of these data demonstrates that the testis is a site of early viral localization that fails to elicit an immunological response, and that HIV‐seropositive men produce infected spermatozoa that are released in the genital tract.—Muciaccia, B., Uccini, S., Filippini, A., Ziparo, E., Paraire, F., Baroni, C. D., Stefanini, M. Presence and cellular distribution of HIV in the testes of seropositive subjects: an evaluation by in situ PCR hybridization. FASEB J. 12, 151–163 (1998)

Expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in undifferentiated nasopharyngeal carcinoma (lymphoepithelioma) and in malignant epithelial tumors.

Immunoreactivity for intercellular adhesion molecule-1 (ICAM-1) and for vascular cell adhesion molecule-1 (VCAM-1), two adhesion molecules of the immunoglobulin (Ig) superfamily, was tested and measured on tissue sections from 16 undifferentiated nasopharyngeal carcinomas (U-NPC), 12 keratinizing squamous cell carcinomas (SCCs) of the head and neck region, and 54 malignant epithelial tumors of various origin. Neoplastic cells of all cases of U-NPC were diffusely and intensely stained for ICAM-1 and VCAM-1. Moreover, ICAM-1 messenger RNA (mRNA) and VCAM-1 mRNA were detected by Northern blot analysis of RNA extracts from two tumors. In the other epithelial tumors focal or diffuse staining for ICAM-1 was observed in 40 cases (66%), whereas reactivity for VCAM-1 was detected in a single case of metastatic undifferentiated carcinoma of unknown origin. The biopsy specimens of U-NPC showed variable infiltration by leukocytes, which were positive for the integrins lymphocyte function antigen-1 (LFA-1) and alpha-4/beta-1, the corresponding ligands for ICAM-1 and VCAM-1. The possibility that ICAM-1 and VCAM-1 on neoplastic cells may favor the intratumoral recruitment of leukocytes in a way similar to that occurring in crypt epithelium of the palatine tonsil is discussed.

Well-differentiated thymic carcinoma: a clinico-pathological study

Well-differentiated thymic carcinoma (WDTC) is a recently described epithelial tumour of the thymus previously classified as cortical or predominantly epithelial thymoma. The authors have reviewed a series of 15 cases of WDTC with the aim of further defining the clinicopathological features of this neoplasm. Histologically, the number of lymphocytes was always low; perivascular spaces and epithelial palisading around blood vessels and/or along fibrous septa were prominent features; 6 cases (40%) were associated with areas of typical cortical thymoma. All cases showed slight to moderate cytological atypia and nuclear grooving was frequently detected. Mitotic activity was variable but usually low. Clinically, all but 3 cases (80%) were invasive at surgery; myasthenia gravis was present in 9 cases (60%); 5 patients (33.3%) died due to disease and 2 additional patients (13.3%) had tumor recurrence. Our study indicates that WDTC has fairly distinctive clinicopathological features and that it is histologically and histogenetically related to cortical thymoma. The definition “well-differentiated carcinoma” is justified because of low-grade cytological atypia and retention of some organotypical histological features, in a tumour otherwise often displaying aggressive and sometimes clear-cut malignant clinical behaviour.

α5 Integrin distribution and TGFβ1 gene expression in supraglottic carcinoma: Their role in neoplastic local invasion and metastasis

Head and neck carcinomas are characterized by tumor‐infiltrating lymphocytes (TIL) producing cytokines. Adhesion molecules, extracellular matrix proteins (ECMPs), and cytokines regulate cell–cell and cell–ECMPs interactions. We investigated the distribution of these proteins to contribute to better understanding of their role in local tumor invasion and metastasis.

Involvement of the bone marrow by non-Hodgkin's lymphomas: incidence, histology and pathologic correlations.

The Lukes and Collins system of classification was applied to 151 cases of non-Hodgkins lymphoma who had bone marrow biopsies taken immediately after histologic diagnosis. Incidence and histologic pattern of bone marrow involvement at the time of initial diagnosis were determined for each subtype of lymphoma. Thirty-three patients (21.8 %) had bone marrow involvement. The frequency of bone marrow involvement was high for undefined and convoluted lymphocyte lymphomas (66.6 %) and low to intermediate for follicular centre cell (20.3 %) and small lymphocyte lymphomas (20.0 %). Within the FCC lymphomas the non-cleaved cell type had a higher incidence of marrow involvement than the cleaved cell type (41.6 % vs 8.9 %). The follicular and diffuse histologic patterns in the diagnostic node did influence the incidence of marrow invasion in the non-cleaved cell type (75 % vs 25 %). A low incidence of marrow involvement was observed for the immunoblastic lymphomas (14.2 %); evidence of marrow infiltration was never observed in patients with true histiocytic lymphoma.

PHA and ConA lymphocyte response in normal, hyperplastic and neoplastic human thymus: Morphologic and functional correlations

In the present work the in vitro response to PHA and ConA was determined for thymus lymphocytes from normal, hyperplastic, and neoplastic conditions as well as for peripheral blood lymphocytes from normal control donors. Our investigation has revealed these results: (1) lymphocytes from normal thymus are less responsive to both mitogens than lymphocytes from peripheral blood and abnormal thymus. (2) Lymphocytes from thymic benign lymphoid hyperplasia show an increased response only to PHA regardless of the extent of hyperplasia. (3) Lymphocytes from thymic neoplasia display an increased response to both mitogens regardless of the histologic pattern of the tumor studied. (4) Thymic lymphocytes from patients with myasthenia gravis have a mitogenic response higher than that from thymic lymphocytes from nonmyasthenic subjects. (5) In patients with myasthenia gravis, lymphocytes from neoplastic thymus show a response to PHA higher than that observed for lymphocytes from hyperplastic thymus. It seems clear that two conditions maximally enhance mitogenic response of thymus lymphocytes: thymomas and myasthenia.

[Effects of a single dose of antilymphocyte serum on tumors induced in mice by 7,12-dimethylbenz(a)anthracene injected at birth].

The effects of ALS (anti-lymphocyte serum) and NRS (normal rabbit serum) treatments on the development of malignant lymphoma, lung, subcutaneous and skin tumors induced in mice by 7,12-dimethylbenz (a) anthracene (DMBA) are described. Groups of Charles-River mice, injected at birth with a dose of 100 μg of DMBA, received a single injection of ALS or NRS at the same time as DMBA administration or 10, 20, 30, 40 and 50 days after birth. Incidence, latency, histology and spread of the tumors were studied in all groups. It was found that both ALS and NRS increased tumor incidence and shortened their latency period. Malignant lymphomas were the main tumors whose latency was shortened either by ALS or NRS treatment. In addition ALS treatment apparently increased dissemination of DMBA induced lymphoma in bone marrow.

[Effects of repeated administration of antilymphocyte serum on tumors induced in mice by 7,12-dimethylbenz(a)anthracene injected at birth].

The present paper describes the effects of repeated administration of rabbit anti-mouse lymphocyte serum (ALS) or normal rabbit serum (NRS) on tumors induced in Charles–River mice by 7,12-dimethylbenz (a) anthracene (DMBA) given at birth. ALS or NRS were given at the same time of DMBA administration and subsequently at weekly intervals for the first 10 weeks of life or at daily intervals for 7 days during the first, second, third or fourth week of life. Incidence, latency, diffusion and histology of the tumors were studied. It was found that either chronic administration of ALS or treatment of very young mice with the serum, greatly reduced the mean survival time of mice, markedly increased the number of tumor bearing mice and the incidence of all histological types of tumors, and decreased their latency period. Administration of ALS in the other experimental groups gave results essentially similar to those observed in DMBA control and NRS treated mice.

Fibrosarcoma of the thymic region. A case report.

Fibrosarcoma of the mediastinum is an unusual tumor and only few cases have been reported. We describe the clinical and pathologic findings of a case of mediastinal mass in a 34 year old woman. The histologic, histochemical, immunocytochemical and ultrastructural features of the tumor were consistent with a diagnosis of fibrosarcoma. Furthermore, the tumor displayed evidence of close relations with the thymus capsule; the possibility that it may arise from the thymic stroma is considered. The differential diagnosis of spindle cell tumors of the mediastinum is also discussed.