Metastases of clinically occult testicular seminoma mimicking primary extragonadal retroperitoneal germ cell tumors.

BACKGROUND: Whether extragonadal germ cell tumors develop primarily in the retroperitoneum or whether they are essentially metastases of a primary testicular tumor has long been debated and remains controversial. PATIENTS AND METHODS: Three patients presenting with apparent primary extragonadal retroperitoneal germ cell tumors are reported. Ipsilateral testicular evaluation was extended with palpation, ultrasonography and finally histological examination. RESULTS: The retroperitoneal extragonadal tumors were found during abdominal MSCT. It was a fortuitous finding in the two first patients.The third patient presented with abdominal pain attributed to necrosis of the large mass which was subsequently firstly drained through endoscopic ultrasound-guided transduodenal puncture. The seminomatous nature of the retroperitoneal tumors was obtained through transduodenal echoendoscopic-guided cytopuncture in the first case, celioscopic resection in the second case and delayed percutaneous CT guided biopsy in the third symptomatic case. The first two patients had a history of cryptorchidism with substantial clinical testicular atrophy; ultrasonography showed microlithiasis and a small intratesticular tumor in the first patient and an hypoechoic but rather homogeneous atrophic testis in the other; orchiectomy confirmed small seminomatous intratesticular tumors in the two cases. The third patient had an atypical hypoechoic area on testicular ultrasound and histopatholgy revealed a burn-out primary tumor. CONCLUSIONS: So-called primary extragonadal retroperitoneal germ cell tumors are extremely rare and should first be considered as metastases of a viable or burned-out testicular cancer until proven otherwise. All ipsilateral testicular abnormalities revealed by the patient's history, clinical examination and mostly by testicular ultrasound must be treated adequately with orchiectomy because they may act as a sanctuary for later tumor growth.

Clinical and pathological features of 14 non-Hodgkin's lymphomas associated with coeliac disease.

BACKGROUND: It is well established that enteropathy associated T-cell lymphoma is associated with malabsorption which is due to gluten sensitivity (coeliac disease). Our study was performed to define the clinical features, histological subtypes, response to treatment, and outcome of the association of coeliac disease and T-cell lymphoma. PATIENTS AND METHODS: A retrospective study was performed in the UCL Group of Hematology to collect data on patients with a diagnosis of non-Hodgkin's lymphoma and coeliac disease. Fifteen cases were observed between 1985 and 1999. Case records for all but one patient were available and the pathological specimens of 14 patients were reviewed by two pathologists. RESULTS: Six previously diagnosed coeliac patients developed lymphoma; interval between coeliac symptoms and onset of the lymphoma ranged from 2 to 48 years (median 16 years). Five patients had coeliac disease and non-Hodgkin's lymphoma diagnosed concomitantly or less than 6 months before the symptoms leading to the diagnosis of lymphoma. Three patients had the diagnosis of coeliac disease after lymphoma diagnosis (1, 8 and 10 years later respectively). Ten non-Hodgkin's lymphomas were of T-cell origin and 4 were B-cell lymphomas. Eight out of 14 presented on a surgical emergency. Thirteen were treated using chemotherapy. The median survival from the diagnosis of enteropathy associated T-cell lymphoma was 12 months (range 1-126). CONCLUSIONS: Lymphomas associated with coeliac disease are heterogeneous and their diagnosis is difficult. The enteropathy-associated T-cell lymphoma is the most frequent, aggressive and fatal complication of coeliac disease but it is not rare to observe association with B-cell lymphoma. Chemotherapy is highly toxic in those patients. Despite a poor prognosis, long-term survival can be expected in a fraction of these patients.

Effect of immunization of hamsters against recombinant P26h on fertility rates.

Despite the various contraceptive methods available, an effective and inexpensive method remains to be established. Immunocontraception may help to achieve this goal. P26h has been proposed as a candidate for the development of a male contraceptive vaccine. P26h, a hamster sperm protein, interacts with the zona pellucida. Furthermore, in vivo fertilization can be blocked completely by active immunization of male hamsters against P26h. Maltose binding protein (MBP)-P26 shares antigenic determinants with the native P26h present on cauda epididymal spermatozoa. The aim of the present study was to reproduce the immunocontraceptive properties of native P26h by immunizing male hamsters against a recombinant P26h fused with a maltose binding protein (MBP). Active immunization of male hamsters with the MBP-P26h showed that specific anti-P26h circulating IgGs could be generated. Mating of immunized male hamsters with superovulated females resulted in a significant decrease, 20-25%, in the fertilization rate. This result is in agreement with results from in vitro sperm-zona pellucida binding assays. Indeed, the anti-recombinant P26h IgGs showed lower inhibitory properties when compared with anti-native P26h IgG. Despite the high anti-P26h IgG titres generated in hamsters, histological studies showed that active immunization has no pathological sequelae to the reproductive tissues. The potential of P26h as a candidate for a contraceptive vaccine is discussed.

Acute leukaemia in paroxysmal nocturnal haemoglobinuria. Case report and review of the literature.

Paroxysmal nocturnal haemoglobinuria (PNH) terminating in acute leukaemia (AL) is an infrequent condition. In several cases, flow cytometric analysis of glycosylphosphatidylinositol anchored membrane proteins such as DAF and CD59/MACIF has suggested the leukaemic cells to be derived from the PNH clone, thereby implicating PNH as a potential preleukaemic disease. In the present paper, we review the data for one patient treated in our hospital and 20 cases reported in the literature from 1969 to 1993. The sex ratio is 1 female/2 males, mean age at diagnosis of PNH was 46 years and the mean interval between the diagnoses of PNH and AL was 53 months. AL type was AML M6 in 8 patients, other types of AML in 12 and ALL in one, with a mean survival of 7.1 months following diagnosis of AL. In all cases analyzed, the PNH phenotype of erythrocytes disappeared with progression of AL, whereas reappearance of this phenotype with complete remission of AL was inconstant. PNH would thus appear to be a potential preleukemic disease. When this disorder terminates in AL, the type is often AML M6, although ALL is also possible. The prognosis of AL in PNH is poor as for other secondary leukaemias. Apart from marrow aplasia, leukaemic transformation is another life threatening complication of PNH which may justify allogeneic bone marrow transplantation (allo-BMT) and potential leukaemic transformation can therefore be an additional argument in favour of allo-BMT when pancytopenia develops in PNH patients.

Infectious complications after 2-chlorodeoxyadenosine therapy.

Infection is a common adverse event after therapy with nucleoside analogs, including 2-chlorodeoxyadenosine (CdA). However, the incidence of CdA-related infections has been poorly documented. In this study we compare, in the same patient population, the incidence of infectious episodes during the 6-month period before CdA to their incidence during the 6 months after initiating therapy. Ninety-five patients with hematological malignancies were studied. The incidence of infectious episodes almost doubled after CdA (0.87 vs. 0.47 during the pre-CdA period). The following factors were associated with an increased risk of infection after therapy: a history of previous chemotherapy, infection during the pre-CdA period and a diagnosis of chronic lymphocytic leukemia or of non-Hodgkin's lymphoma. Age, neutrophil and lymphocyte count at onset of CdA and time interval between diagnosis and therapy with CdA did not correlate with the infectious risk. The pattern of infections was modified after therapy with an increase of herpes virus infections ( 1 vs. 8 episodes, p=0.04) and of fever of unknown origin (6 vs. 17 episodes, p=0.03). In conclusion, a population at high risk for developing infectious complications after CdA therapy can be identified. Specific measures aimed at reducing the incidence of infectious events should concentrate on this population.

2-Chlorodeoxyadenosine therapy in advanced chronic lymphocytic leukaemia.

The therapeutic potential of 2-chlorodeoxyadenosine (CdA) in patients with advanced chronic lymphocytic leukaemia (CLL) remains controversial with response rates in clinical trials ranging from 44 to 67%. This report describes our experience with CdA in 22 CLL patients having already undergone previous treatment. CdA was given by continuous intravenous infusion at a dose of 4 mg/m2/day for 7 days (4 patients) or as 2-h intravenous infusions at a dose of 5.6 mg/m2/day for 5 days (18 patients). Partial (n = 5) or complete (n = 2) response was obtained in 7 cases. As compared to unresponsive patients, responding subjects received CdA earlier in the course of their disease (mean interval between diagnosis and CdA therapy 58 vs 102 months), were less thrombocytopenic at initiation of CdA (mean platelet count 165 x 10(9)/L vs 81 x 10(9)/L) and experienced less severe neutropenia during the first course of therapy (mean minimal neutrophil count 1.55 x 10(9)/L vs 0.43 x 10(9)/L). None of 6 patients with CLL refractory to fludarabine responded to CdA. An evaluation of haematological toxicity during the first course of treatment showed grade 4 neutropenia (< 0.5 x 10(9)/L) in 7 cases and grade 4 thrombocytopenia (< 25 x 10(9)/L) in one of 19 cases where the platelet count was greater than 25 x 10(9)/L at initiation of CdA. In comparison with earlier reports, the present series of patients had received relatively heavy prior therapy, experienced more severe haematological toxicity and demonstrated a lower total response rate.

[Anorectal anaplastic cancer (neuroendocrine)]. / Cancer anaplasique (neuro-endocrinien) anorectal.

An extensive case of undifferentiated neuroendocrine carcinoma with small cells of the anorectal region is reported. The carcinoma is related to pulmonary anaplasia and quite rare in the colonic and rectal region. Its aggressivity is considerable with a strong propensity for hematogenous and lymphatic metastases and with a disastrous prognosis: 0% survival over 1 year. The incidence, the characteristic features, the histogenesis, and the anatomical pathology of this rare neoplasm are mentioned. Furthermore, the case illustrates a radiological pattern typical for major lymphatic dissemination with an intra- and extraparietal component. The mechanism of dissemination is explained by the "lymphatic block" theory. The absolute necessity of obtaining an histology in radiologically unusual and/or extensive cases is mentioned.

Classification of immature and mature cells of the neutrophil series using morphometrical parameters.

Quantitative morphological data of six classes of immature and mature cells of the neutrophil series of the bone marrow of normal persons were used for statistical classification experiments (myeloblasts, promyelocytes, myelocytes, metamyelocytes, bands and segments). On each cell, parameters were measured directly from the image or calculated from the shape of the density histogram or the counting densitogram using a Texture Analysis System (E. Leitz, Wetzlar, Germany). The parameters were analyzed with the interactive statistical pattern recognition system ISPAHAN. One half of the data were used as a learning set and the other half as the test set. The parameters were compared according to their performance in discrimination between the classes, alone and in combinations. Parameters not contributing to an improvement of the discrimination were disregarded. Eleven parameters were selected and used for classification by two different methods: a stepwise and a "one-shot" method. Stepwise classification resulted in a 79% correct classification rate. Most errors occurred between cell classes in neighboring stages of maturation. In 96% of all cases the computer classification was either in accordance with that of the technician or with a cell class of a neighboring maturation stage. One step classification by the computer was in agreement with the technicians in 82% of the cases. For 98% of the cells the computer classification was either in accordance with that of the technician or with a cell class of a neighboring maturation stage. The data set was collected by two technicians, operating independently. Differences in their interpretation of the maturation stage were found by comparing the performance of classifiers based on both cell samples. Since the images of the cells were not available for reexamination, the causes of disagreement in classification between the technicians and between computer and technicians could not be evaluated.

Relevance of morphometric parameters for the classification of normal white blood cells.

An interactive morphometry system (Leitz T.A.S.) was used to extract 39 parameters from 1506 cells of five normal WBC classes. The data set was split in a learning set and a test set, and the value of each single parameter and of combinations of parameters was assessed with the interactive pattern recognition system ISPAHAN. A combination of nine densitogram parameters gave a correct classification in 92.6%; adding four geometrical and seven counting densitogram parameters improved this to 98.5%. It appeared that simple measurements are sufficient for a correct differentiation into the normal white blood cell types. In a pilot study fo 40 normal myeloid bone marrow cells of four classes a correct discrimination between mature and immature cells was reached in 93%. Extraction of parameters with the T.A.S. and their subsequent evaluation with ISPAHAN appeared to be an efficient method of white blood cell classification probably including immature cell types.

Texture of white blood cells expressed by the counting densitogram.

The counting of particles and holes in white blood cells during thresholding at different gray levels results in a histogram, the counting densitogram, which contains information about granularity. Parameters describing the shape of this histogram appear to be sufficiently characteristic for the five normal white blood cell classes to allow a 84% correct discrimination between them. This method to quantitate granularity could be valuable for the analysis of cell texture and therefore, when used in combination with geometrical and density histogram parameters, could contribute to the results of morphometric discrimination between other than normal white blood cells.