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Lung cancer at the University College Hospital, Ibadan, Nigeria.

A 30-year retrospective review of cases of lung cancer from the Cancer Registry of the University College Hospital (UCH), Ibadan Nigeria was carried out. A total of 142 cases were analyzed with a male:female ratio of 1.7:1. Peak age incidence in females was 2 decades (4th) earlier than for males. Squamous cell carcinoma was found most commonly but adenocarcinoma predominated in females. Mucoepidermoid and adenoidcystic carcinomas were absent. About 27% of patients were under 40 years old and the majority of these (82%) showed the bad prognosis histological variants (i.e. anaplastic carcinoma, adenocarcinoma, small cell tumours and sarcomas). At autopsy the original lymph nodes were founded to be most commonly involved by secondary metastases while the spinal cord was least involved. The epidemiology of malignant lung tumours in Ibadan probably differs from that in the more industrialized countries and this suggests a different view of risk factors for this environment. Additionally there is an urgent need for developing methods for earlier diagnosis if the mortality associated with this disease is to be reduced especially as it occurs predominantly in young people.

Adolescent↗

[Classification and terminology of malignant lung neoplasms (polemic aspects].

The article deals with the different aspects of classification in oncopulmonology. The authors introduce their correction and suggest to discuss in the form of polemics the clinico-anatomical systematization of malignant pulmonary tumors and the gradation of carcinoids, sarcomas, and small-cell carcinoma of the lung according to stages and the TNM system, and to systematize the operative interventions.

Humans↗

Frequency of bone marrow involvement in non-haematological malignancies.

Five hundred and fifty two bone marrow (BM) specimens (497 aspirates, 55 biopsies) from 518 patients with nonhaematological malignancies were examined to determine the frequency of metastatic deposits. BM involvement was highest in neuroblastoma (9/14), prostate cancer (2/4), retinoblastoma (3/7), Ewing's sarcoma (14/47), rhabdomyosarcoma (5/20) and small cell carcinoma of lung (3/18). BM aspiration smears were adequate in paediatric tumours (neuroblastoma, retinoblastoma, rhabdomyosarcoma) while BM biopsies were most useful in patients with Ewing's sarcoma, prostate cancer and small cell lung cancer. We conclude that BM is an easy investigation in the diagnosis and staging of nonhaematological cancers.

Bone Marrow↗

Immunoexpression of villin in neuroendocrine tumors and its diagnostic implications.

BACKGROUND: Villin, a 95-kd cytoskeletal protein associated with axial microfilament bundles of brush border microvilli, is mostly restricted to intestinal glandular tumors. Villin immunoexpression was recently observed in a small number of carcinoids of the intestinal tract and lung, but its significance in a broad category of neuroendocrine tumors has not been evaluated. DESIGN: A total of 114 neuroendocrine tumors of different origins were tested for villin expression. They included gastrointestinal carcinoids (n = 30), lung carcinoids (n = 15), small cell carcinomas of the lung (n = 24), small cell carcinomas of other sites (n = 15), islet cell tumors (n = 8), Merkel cell carcinomas (n = 6), paragangliomas (n = 6), and others (n = 10). Nine round cell sarcomas were tested as well. RESULTS: Villin immunoreactivity was present in 85% of gastrointestinal carcinoids and small cell carcinomas, but was found in only 40% of lung carcinoids. Other tumors tested were virtually negative for villin. In general, while cytoplasmic reactivity was most common, a characteristic apical membranous pattern simulating brush border was seen in 76% of the gastrointestinal carcinoids and in 50% of the lung carcinoids. CONCLUSIONS: We found that villin was predominantly restricted to gastrointestinal neuroendocrine tumors (excluding islet cell tumors), although a small number of bronchial carcinoids may be positive as well. These results suggest a role for villin in the differential diagnosis of neuroendocrine tumors.

Adenoma, Islet Cell↗

[Cytogenetics of bone sarcomas].

There has been much progress in the cytogenesis, and molecular biology of bone tumours such as Ewing sarcoma and osteosarcomas, greatly improving diagnostic possibilities and prognosis. Ewing's sarcoma is an indifferentiated sarcoma with round cells which usually occurs in children or adolescents. Ewing's sarcoma corresponds to 6% of all bone tumours. Histologically Ewing's sarcoma belongs to a group of small round cell tumours including neuroblastoma, embryon and alveolar rhabdomyosarcoma and non-Hodgkin's lymphoma. Differential diagnosis is difficult. Cytogenetic examinations can now differentiate Ewing's sarcoma from other small round cell tumours. There is a specific 11:12 translocation (q24; q12) which can be used as a marker.

Adult↗

Cytogenetic characterization of selected small round cell tumors of childhood.

Small, round, blue-cell tumors (SRCT), including rhabdomyosarcoma, Ewing's sarcoma of bone and soft tissue, mesenchymal chondrosarcoma, small cell osteosarcoma, hemangiopericytoma, neuroblastoma, peripheral neurectodermal tumor (peripheral neuroepithelioma of bone and soft tissue), and the malignant small cell tumor of the thoracopulmonary region described by Askin (Askin's tumor), are often difficult to distinguish by light microscopy. We have evaluated the cytogenetics of these tumors by studying 24 tumor explants in short-term culture and 22 tumor cell lines. In Ewing's sarcoma (a tumor of unknown histogenesis), and in peripheral neuroepithelioma and Askin's tumor (tumors with evidence of neural origin), we have observed an indistinguishable t(11;22) translocation.

Adolescent↗

The p19INK4D cyclin dependent kinase inhibitor gene is altered in osteosarcoma.

Inhibition of cyclin dependent kinases (CDK) by cyclin dependent kinase inhibitors (CDKI) blocks cell cycle progression and inhibits cellular proliferation. The archetypical member of the INK4 CDKI family, p16INK4A (also called CDKN2), is a tumor suppressor frequently deleted or mutated in certain neoplasms and many cell lines. Because p19INK4D has strong structural and functional similarity to p16INK4A, we have assessed its role as a tumor suppressor. This was accomplished by screening the p19INK4D coding region for mutations, deletions and rearrangements in sarcomas and non-small cell lung cancers. Alterations of the p19INK4D gene were found in samples from five of 67 (7%) patients with osteosarcomas and none were found in other types of sarcomas or in lung cancers. Five osteosarcoma samples had Southern blot patterns consistent with gene rearrangement. These samples included a primary and recurrent osteosarcoma from the same patient; both with the same rearrangement. Four samples had SSCP patterns consistent with sequence alterations, sequencing determined that three were due to silent base changes and apparently polymorphisms. Sequencing the fourth shifted band revealed a one base insertion causing a frameshift beginning with codon 27. In summary, these studies found alterations affecting the p19INK4D gene in a small but significant number of osteosarcomas. Presumably, abnormalities of this gene contribute to the development of cancer of bone cells.

Carrier Proteins↗

Immunocytochemistry in fine needle aspirates of small cell-, round-, blue-cell malignant tumors of childhood (neuroblastoma, nephroblastoma, lymphoma, Ewing's sarcoma, rhabdomyosarcoma).

Immunocytochemistry with the use of monoclonal antibodies to vimentin, keratin, desmin, neurofilaments and leukocyte common antigen (LCA) was applied to 53 fine needle aspirates of small cell-, round-, blue-cell malignant tumors of childhood (neuroblastomas, nephroblastomas, non-Hodgkin's lymphomas, Ewing's sarcomas and rhabdomyosarcomas). The results revealed the following immunophenotypes: neuroblastomas were positive for neurofilaments. Nephroblastomas contained vimentin (in blastema cells), keratin (in epithelial and blastema cells) Non-Hodgkin's lymphomas were vimentin and LCA positive, keratin negative. Ewing's sarcomas displayed multidirectional differentiation. Rhabdomyosarcomas were desmin and vimentin positive. It is concluded that immunocytochemistry in fine needle aspirates should be used as an objective evidence to support morphologic differential diagnosis of small cell-, round-, blue cell malignant tumors of childhood.

Biopsy, Needle↗

Needle aspiration biopsy in the diagnosis of lytic bone lesions in histiocytosis X, Ewing's sarcoma and neuroblastoma.

Cytologic smears obtained by needle aspiration biopsy of lytic bone lesions in 15 patients with histiocytosis X, Ewing's sarcoma and neuroblastoma were reviewed. After conventional staining, histiocytosis X could be diagnosed and differentiated from small cell tumours such as Ewing's sarcoma and neuroblastoma. The need for sampling material for cytochemical and ultrastructural analysis of these small cell tumours by needle aspiration is emphasized.

Adolescent↗

Clinical implications of nodal reactive follicular hyperplasia in the elderly patient with enlarged lymph nodes.

In older persons, the humoral immune response, as reflected morphologically by proliferation and expansion of germinal centers, is relatively subdued in comparison with the florid reactive follicular hyperplasia (RFH) which may be observed in younger age groups. The presence of RFH in lymph node biopsies in patients 60 yr or older, which we have regarded with concern since 1972, appears to represent an imbalance of the immune system, in some patients, on the background of which predominantly non-Hodgkin's malignant lymphoma (NHL) may be present or will develop. Fifty-eight patients 60 yr old or more who presented with enlarged lymph nodes exhibiting inappropriate RFH for age were identified during the interval from 1969 to 1989. An apparent etiology was initially identified for the reactive follicular hyperplasia in only 12 cases: five with documented rheumatoid arthritis; one each with a history of trauma, positive monospot test, and combination of thrombophlebitis and fungal skin infection, and two each with elevated Epstein-Barr virus (EBV) titers and human immunodeficiency virus type 1 (HIV-1) seropositivity. While most were alive or died of nonlymphomatous causes and one was lost to follow-up, 18 (31%) patients either had concurrent lymphoma or subsequently developed diffuse NHL. There were ten diffuse interfollicular (I-Foll) lymphomas (six concurrent), two diffuse mixed cell lymphomas (DMCL), one diffuse large cell lymphoma (DLCL), one diffuse immunoblastic sarcoma (DIBS), two diffuse small noncleaved cell lymphomas (DSNCL), one unclassified NHL, and only one Hodgkin's disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Neuron-specific enolase and Leu-7 immunoreactive small round-cell neoplasm. The relationship to Ewing's sarcoma in bone and soft tissue.

The authors present an immunohistochemical analysis of tissue from five cases of morphologically distinctive Ewing's sarcoma in bone and soft tissue. The mean age of the five patients was 16.6 years, with a range of 6-28 years. The tumors existed in chest wall, pelvis, and lower extremities. Two siblings with tumor in bone were clinically diagnosed as having Ewing's sarcoma. All cases had immunoreactivity for neuron-specific enolase (NSE), and four cases revealed positive staining for Leu-7. Neuron-specific enolase is highly specific for neurons and neuroendocrine cells. In addition, immunoreactivity for Leu-7, expressing a natural killer activity, has been demonstrated in peripheral nerve fibers and neuroendocrine cells. The authors suggest that NSE and Leu-7 immunoreactive small round-cell neoplasm is probably a primitive neuroectodermal tumor and should be categorized as Ewing's sarcoma in bone and soft tissue.

Adolescent↗

Extraskeletal Ewing's sarcoma presenting with pulmonary embolism.

Small round cell tumours with the morphologic characteristics of Ewing's sarcoma arise rarely in soft tissues of the extremities, retroperitoneum, chest and orbit. Patients usually present with symptoms arising from the swelling at the primary site. We report on a patient with a retroperitoneal extraskeletal Ewing's sarcoma who presented with massive tumour embolism to the pulmonary vasculature. To our knowledge, this is the first report of extraskeletal Ewing's sarcoma presenting with pulmonary tumour embolism.

Adult↗

Angiogenesis and prediction of sarcoma formation by plastic.

The capacity to induce new formation of capillaries was tested in cells attached to plastics. It is known that large plastic coverslips implanted s.c. in CBA mice produce sarcomas more rapidly and in a greater number than do small coverslips. We observed that within a few weeks after implantation the cells attached to the large coverslips showed an angiogenic capacity about 5-fold greater than that of the cells attached to the small coverslips. Months before a sarcoma was evident, angiogenesis induced by the cells attached to the large coverslips predicted the high risk of neoplastic transformation by large coverslips.

Animals↗

Angiotensin-induced hypertension chemotherapy in children with advanced solid tumors.

Angiotensin-induced hypertension chemotherapy (IHC) was investigated in six children with the following advanced malignancies: hepatocellular carcinoma, extraskeletal Ewing's sarcoma, sacrococcygeal malignant teratoma, small round cell tumor of the chest wall, hepatoblastoma and osteogenic sarcoma. Partial response was achieved in three of these patients, two showed no change, and in one IHC was used as adjuvant chemotherapy. The side effects of IHC were minimal and tolerable. Angiotensin-IHC may provide a new approach to pediatric cancer chemotherapy.

Adolescent↗

The clinical development of paclitaxel and the paclitaxel/carboplatin combination.

Paclitaxel and carboplatin have nonoverlapping toxicities with a broad range of clinical activity. The combination of escalating dose paclitaxel and carboplatin dosed to a fixed area under the curve (AUC) was explored in a series of phase I studies. 76 patients were treated with paclitaxel over three hours followed by a 30 min carboplatin infusion, dosed by the Calvert formula to a target AUC of 4.0 or 4.5 mg/min/ml-1. The maximum tolerated dose of paclitaxel was 270 to 290 mg/m2, with a dose limiting toxicity of peripheral sensory neuropathy. Activity was seen in lung cancer, with a paclitaxel dose at or above 230 mg/m2. Neuropathy correlated with paclitaxel AUC due to nonlinear pharmacokinetics at higher doses. Ongoing studies include the use of amifostine as a neuroprotectant and phase II studies of the paclitaxel/carboplatin regimen in head and neck cancer, small cell lung cancer and sarcomas.

Adult↗

Congenital alveolar rhabdomyosarcoma with multiple skin metastases. Report of a case.

A rare case of congenital alveolar rhabdomyosarcoma revealing multiple skin metastases in a female neonate is reported. At birth, a ping-pong ball-sized tumor on the neck and a tumor the size of a little finger end on the chin were noticed. Then, multiple skin tumors over the whole body occurred soon after birth. A biopsied small skin tumor was at first interpreted as being compatible with metastatic congenital neuroblastoma. However, immunohistochemical and electron microscopic findings revealed positive immunoreactivity for myoglobin in a few tumor cells and the presence of a few rhabdomyoblasts among poorly differentiated tumor cells, resulting in a final diagnosis of alveolar rhabdomyosarcoma. Therefore, it should be emphasized that in cases of round cell tumor, immunohistochemical and ultrastructural studies are imperative in order to identify the tumor and differentiate it from other forms, including rhabdomyoblastoma, neuroblastoma, Ewing's sarcoma, malignant lymphoma, and small cell carcinoma.

Alveolar Process↗

[Recent views on the functional histological classification of malignant lymphomas].

The recent immunological classification of malignant lymphoma (ML) proposed by Lukes and Collins is examined. It is based on morphological changes linked to the dynamics of the reactive or secondary follicular clear centres. B-cells (follicular centre) are small or large and may cleft or not; they may proceed to macrophage or plasma cell types. T cells (around the follicles) are small and round, and have a convolute nucleus. ML types are distinguished by the predominance of one cell element, or by a mixture of cells from the maturative line of the follicular centre, i.e. T-cell (or convolute) lymphomas and B-cell (or follicular centre) lymphomas. Stem cells have none of these features. The classification was applied in a series of 32 non-Hodgkin and 24 Hodgkin ML's. Of the former, 23 were classed as B-cell types: 8 small and 5 large cleft cells; 7 small and 3 large non-cleft cells. The remainder were: 2 B-cell immunoblastic sarcomas, 3 histiocyte ML, 2 small lymphocyte ML, 1 ML with convolute lymphocytes, and 1 case with indeterminate cells ("stem cell lymphoma"). The 24 Hodgkin cases were classified in accordance with Rye's pattern (based on the work of Lukes et al.). It was noted that the numerical prevalence of convolute cells gradually fell, passing from lymphocyte dominance to lymphocyte depletion. At the same time, there was an increase in follicular centre cells and a diminution of plasma cell tending lymphocytes. The problems raised by this new immunological and morphogical classification of ML are discussed.

Adolescent↗