Mantle cell lymphoma associated with hyper-IgE syndrome

A 69-year-old woman was admitted with generalized lymph node swelling and huge splenomegaly. CD5(+), Sm-IgM (+) and SmIgD (+) lymphocytes were increased in lymph nodes, spleen and bone marrow, and she was diagnosed as having mantle cell lymphoma. A diagnosis of hyper-IgE syndrome was also made, because IgE was markedly increased (174,780 u/ml) and chronic dermatitis, which was often complicated with infection, occurred repeatedly on her extremities. In this case, interleukin-4 was considered to be one of the factors involved in the hyper-IgE syndrome, because increased IgG1 and reduced IgG2 were observed. Immunological abnormality associated with the hyper-IgE syndrome seemed to contribute to the development malignant lymphoma in this case.     

Primary non-Hodgkin lymphoma of the sinonasal cavities: correlation of CT evaluation with clinical outcome

PURPOSE: To determine retrospectively the primary site of origin of sinonasal lymphomas with computed tomography (CT) and correlate the CT findings with histologic phenotype and clinical outcome. MATERIALS AND METHODS: In 24 patients with stage I and II non-Hodgkin lymphomas of the sinonasal cavities, the CT appearances and clinical data were reviewed retrospectively. RESULTS: The sites of primary tumor determined at CT were the nasal cavity in 13 patients, the ethmoidal sinus in three patients, and the maxillary sinus in eight patients. B-cell lymphomas were found mainly in the maxillary sinus, while T-cell lymphomas were found in the nasal cavity and ethmoidal sinus (P < .005). The 5-year survival rates in relation to the primary site of the tumor were 64% for the nasal cavity, 50% for the ethmoidal sinus, and 100% for the maxillary sinus (P = .26). CONCLUSION: Patients with B-cell primary lymphoma of the maxillary sinus tended to have a good prognosis in contrast to those with T-cell lymphomas that originated from midline structures. The primary site determined at CT appears to be correlated with the histologic phenotype and clinical outcome.     

Mantle cell lymphoma: a clinicopathologic study of 80 cases

Mantle cell lymphoma (MCL) is a relatively uncommon yet distinct type of malignant lymphoma whose clinical and pathological characterization has been limited by the small numbers of cases published to date. We studied 80 cases of MCL seen at a single institution over 7 years to determine both clinical and pathological prognostic factors. The patients in this study were predominantly male (70%) and older (mean age, 63 years) and presented with advanced-stage disease (88%). Extranodal involvement was common. Median overall survival (OS) was 43 months. Except for performance status, prognosis was not significantly influenced by clinical prognostic factors. Histologically, MCL architecture was classified as diffuse (78%), nodular (16%), or mantle zone (6%); the OS among these groups was identical. Increased mitotic activity (>20 mitotic figures per 10 high power fields), blastic transformation, and peripheral blood involvement at diagnosis also predicted for a worse outcome, but bone marrow involvement did not. The presence or absence of a translocation t(11; 14) by cytogenetic analysis or a bcl-1 rearrangement by Southern analysis did not significantly predict outcome. In summary, this study of 80 cases of MCL highlights its distinctive clinicopathologic features and shows that increased mitotic activity, blastic morphology, and peripheral blood involvement at diagnosis are prognostically important factors.     

Cytogenetic profile of lymphoma of follicle mantle lineage: correlation with clinicobiologic features

Conventional chromosome analysis (CCA) and interphase fluorescence in situ hybridization (FISH) was performed in 42 patients with mantle-cell lymphoma (MCL), with BCL1 rearrangement. The t(11;14)(q13;q32) or 11q abnormalities were detected by CCA in 34 cases, 20 of which had additional aberrations. A normal karyotype was observed in 8 cases. Probes detecting the chromosome aberrations that were observed in at least 3 cases by CCA, ie, +12, 13q14 deletion, and 17p deletion, were used for interphase FISH analysis. FISH detected total or partial +12, 13q14 deletion and 17p- in 28.5%, 52.4%, and 26% of the cases, respectively. The presence of these anomalies was not a function of karyotype complexity. Based on the results of CCA/FISH, three groups of increasing karyotype complexity were recognized: group 1, including 11 patients without detectable aberrations in addition to BCL1 rearrangement; group 2, including 14 patients with 1 to 2 additional anomalies; and group 3, including 17 patients with three or more additional anomalies. Clinical parameters associated with shorter survival were male sex (P =.006) and primary lymph-node involvement compared with primary bone marrow involvement (P =.015). Trisomy 12 was the only single cytogenetic parameter predictive of a poor prognosis (P =.006) and the best prognostic indicator was the derived measure of karyotype complexity (P <.0001), which maintained statistical significance in multivariate analysis (P<.0001). We arrived at the following conclusions: 13q14 deletion occurs at a high incidence in MCL; 17p deletion and total/partial +12 are relatively frequent events in MCL, the latter aberration being associated with a shorter survival; and the degree of karyotype complexity has a strong impact on prognosis in this neoplasia.     

Amplification of 11q13 DNA markers in head and neck squamous cell carcinomas: correlation with clinical outcome

This study was performed on 282 patients with primary head and neck squamous cell carcinomas to evaluate the prognostic importance of 11q13 amplification. Amplification of the 11q13 DNA markers, HST-1/FGF-4 and BCL-1, evaluated by Southern and slot blot hybridisation, was detected in 52% of tumours. 11q13 amplification was associated with tumour site since this alteration occurred in 76% of tumours arising in the hypopharynx, versus 40% in the other sites (P = 0.0007). 11q13 amplification was also significantly related to the presence of involved neck lymph nodes (P = 0.013). The relationship between 11q13 amplification and risk of progression was studied in two subgroups of head and neck cancer patients with regard to treatment modalities. The presence of 11q13 amplification in the tumour was not significantly associated with a shorter event-free survival (P = 0.82) and crude survival (P = 0.61) of the 201 patients treated by surgery and postoperative radiotherapy. Similarly, absence of a relationship was observed for the group of 79 patients treated by surgery alone. These results confirm that 11q13 amplification is a prominent event in head and neck squamous cell carcinoma, indicating that it may be a common genetic event in the development of these neoplasms, but is not a reliable prognostic marker.     

S-phase fraction of 155 soft tissue sarcomas: correlation with clinical outcome

BACKGROUND: Traditionally, grade is considered the most important prognostic factor for soft tissue sarcomas (STS). However, because of the alleged difficulties in reproducibility of grading, new, objectively determined prognostic factors would be of value. The aim of our study was to establish if S-phase fraction (SPF) measured with flow cytometry was of prognostic significance for STS. METHODS: In this study, we included all 193 adult STS patients with superficial trunk or limb tumors who were treated by the Helsinki University Central Hospital (HUCH) STS group between January 1987 and May 1993. One hundred and seventy-two formalin fixed paraffin embedded tumor samples were available. SPF measurement was successful in 155 cases. RESULTS: Eighty-six cases were diploid. Ploidy was found to have no effect on overall survival. The median SPF was 6.8% (diploid tumors, 4% and nondiploid tumors, 12.9%). A high SPF predicted a shorter survival in patients with diploid tumors (P=0.003). The prognostic value was even stronger when we studied disease specific survival and excluded from analysis samples that contained less than 50% tumor cells (P=0.011). However, no prognostic value could be detected in nondiploid tumors or in the material as a whole. CONCLUSIONS: Our results suggest that high SPF is an adverse prognostic factor for survival of patients with diploid STS. However, further studies are needed to confirm these results.     

Two-way cell traffic between mother and fetus: biologic and clinical implications

The bilateral trafficking of nucleated cells between the fetus and the mother was studied using polymerase chain reaction (PCR)-based systems sensitive enough to detect 1 target cell in 100,000 background cells. Sixty-six mother-baby pairs were recruited; maternal and cord blood samples were collected at delivery for DNA extraction. Cell trafficking was studied in informative cases using PCR-genotyping of polymorphic regions in the beta-globin cluster, the glutathione S-transferase M1 locus and the angiotensin converting enzyme gene. In addition, Y-PCR was also used in conjunction with these systems for the detection of fetal cells in maternal circulation. Fetal cells were detected in maternal peripheral blood in 26 of 51 cases whereas maternal cells were detected in 16 of 38 fetal umbilical cord blood samples. The proportion of umbilical samples with detectable maternal sequences was much higher than previously reported. In the 28 cases informative for both mother and baby, there was no obvious correlation between the cell traffic from mother to baby as compared to that from baby to mother. These findings may have implications for the use of cord blood for bone marrow transplantation, the vertical transmission of infectious agents, and the physiology of the feto-maternal relationship.     

Aphasia outcome in stroke: a clinical neuroradiological correlation

Fourteen aphasic patients with acute onset of thromboembolic cerebrovascular insults demonstrable by angiography or radioscintigrams who were available for long-term follow-up have been studied. Their aphasia evolution was compared with acute angiographical and radioisotopic findings, and the lesions shown by follow-up computerized axial tomography (CT). Angiographical site of occlusion, evidence of early reopening of occluded vessels, and radioisotopic flow asymmetries including the "hot-stroke" luxury perfusion failed to correlate with aphasia outcome. Radioisotopic static images were more helpful by depicting lesion location and number but lacked the definition seen on the CT scan. The long-term CT scan by showing the size, location and number of lesions had a good correlation with aphasia outcome. Those patients with large dominant hemisphere involvements, either one large or many smaller lesions, fared poorly while those with lesser lesions did better. Bilateral lesions, at times evasive clinically, helped to account for significant aphasia residuals.     

K-ras gene point mutations in human endometrial carcinomas: correlation with clinicopathological features and patients' outcome

In order to evaluate the role of K-ras gene point mutations in the progression of endometrial carcinoma, we applied the polymerase chain reaction/restriction-fragment-length polymorphism technique to 57 tumours surgically removed from women of Polish origin. We assessed the relationship between K-ras gene activation and clinicopathological features as well as patients' outcome. Mutational activation in codon 12 of the K-ras gene was detected in 8 out of 57 (14%) endometrial carcinomas, while in codon 13 of the K-ras gene no point mutations were noted. A correlation between the histological type of the tumour and codon 12 K-ras gene mutation was noted (P < 0.05; Fisher exact test). K-ras gene mutation was not related to the patients' age, surgical stage, histological grade or to the depth of myometrial invasion. A trend towards a poorer prognosis was noted during the follow-up of patients whose tumours had shown K-ras codon 12 point mutations, but the difference was not significant (P = 0.06; log-rank test). Our data indicate that point mutations in codon 12 of the K-ras gene are a rare event in human endometrial carcinomas. The lack of correlation between K-ras point mutations and clinicopathological features (except histological type) supports the hypothesis of a random activation of the K-ras gene in human neoplastic endometrium.     

Non-Hodgkin's lymphoma: biologic classification, diagnosis and treatment

The lymphomas are the seventh most common causes of death from cancer in the United States. There is a steady increase in the incidence of non-Hodgkin's Lymphoma from childhood through the age 80, and in the United States, is more common in males than in females. The etiology of the lymphomas is unknown. Molecular biology techniques have allowed the elucidation of many cellular function involved in tumorigenesis. Clinical presentation of non-Hodgkin's lymphoma are varied, and depend on the histologic subtype, the extent (or stage) of the disease, and the primary site of the tumor, most often present lymph node disease, children typically have extranodal disease involving the mediastinum, abdomen or head and neck. Non-Hodgkin's lymphoma are categorized as low, intermediate, or high grade, on the basis of their clinical aggressiveness. Low and intermediate grade tumors predominate in adults, whereas more than 90 percent of children with non Hodgkin's lymphoma have a high grade tumor. The field of cancer therapy has progressed rapidly. In the most recent era, treatment has included multiagent chemotherapy directed to the stage and histologic subtype of the disease. Gene therapy has now become a standard experimental approach for treating cancer were conventional therapies have failed.     

Gender and schizophrenia: association of age at onset with antecedent, clinical and outcome features

Sec7-related guanine nucleotide exchange factors (GEFs) initiate vesicle budding from the Golgi membrane surface by converting the GTPase ARF to a GTP-bound, membrane-associated form. Here we report the crystal structure of the catalytic Sec7 homology domain of Arno, a human GEF for ARF1, determined at 2.2 angstroms resolution. The Sec7 domain is an elongated, all-helical protein with a distinctive hydrophobic groove that is phylogenetically conserved. Structure-based mutagenesis identifies the groove and an adjacent conserved loop as the ARF-interacting surface. The sites of Sec7 domain interaction on ARF1 have subsequently been mapped, by protein footprinting experiments, to the switch 1 and switch 2 GTPase regions, leading to a model for the interaction between ARF GTPases and Sec7 domain exchange factors.     

Serum levels of p55 and p75 soluble TNF receptors in adult acute leukaemia at diagnosis: correlation with clinical and biological features and outcome

The tumour necrosis factor (TNF)/TNF-receptor (TNFR) complex plays a role in the growth of leukaemic cells. We retrospectively investigated the relationship between pretreatment serum concentration of soluble TNFR (p55- and p75-sTNFRs) and outcome in adult acute myeloid (AML 82 cases) and lymphoid (ALL 44 cases) leukaemia. Both sTNFRs were significantly higher in AML (p55-sTNFR 4.53 +/- 3.7, median 3.75; p75-sTNFR 6.51 +/- 5.25 ng/ml, median 4.72) and ALL sera (3.31 +/- 1.5, median 2.95; 5.30 +/- 2.3 ng/ml, median 4.56, respectively) than in controls (1.89 +/- 0.5, median 1.98; 2.22 +/- 0.8 ng/ml, median 2.37) (P < 0.01 for both sTNFRs). Fresh leukaemic cells expressed p55- and p75-sTNFRs, which were modulated and released into the supernatant (SN) following short-term in vitro culture, suggesting that in vivo sTNFRs were also leukaemia-derived. Whereas no correlation was observed between sTNFRs and outcome in ALL, in AML higher p55-sTNFR levels (> 3.75 ng/ml) were associated with shorter disease-free survival (DFS) (P = 0.006) and overall survival (OS) (P = 0.0004). At multivariate analysis p55-sTNFR was the most significant predictor of DFS (P = 0.006) and OS (P < 0.001). Our data suggest that the prognostic significance of p55-sTNFR in AML could be related to relevant biological features of AML blasts.     

Detection of infection with human immunodeficiency virus type 1 before seroconversion: correlation with clinical symptoms and outcome

Early (pre-seroconversion) infection with human immunodeficiency virus type 1 (HIV-1) was identified in 50 of 267 participants in the Multicenter AIDS Cohort Study. These 50 men had a positive EIA result, which detected IgM antibody (n = 35), p24 antigen, or serum HIV RNA (n = 15) at their last "seronegative" visit. At that visit, the mean CD4 lymphocyte number (890/mm3 vs. 1038/mm3) was significantly lower than in men who subsequently seroconverted but had no evidence of early infection. The decline in CD4 cells was slower and the duration of AIDS-free time longer in the 19 men who were symptomatic in comparison to the 31 asymptomatic men with early infection, but differences were not significant.     

Hypothalamic hamartoma: report of a case with unusual histologic features

A rare case of hypothalamic hamartoma with unusual radiologic and histopathological features is described, possibly the first of its type in English literature. A 1.5-year-old female child presented with precocious puberty. MR scan of the brain revealed a pedunculated hypothalamic mass, most of which was isointense with normal brain on T1- and T2-weighted images. However, a sizeable component of the lesion was hyperintense on T1-weighted images, suggestive of adipose tissue. Microscopically, the lesion was a hamartoma composed of an admixture of neuroectodermal elements, namely glial cells, neurons, and nerve bundles along with mesenchymal elements in the form of fibroadipose tissue.     

Malignant lymphoma obscured by concomitant extensive epithelioid granulomas: report of three cases with similar clinicopathologic features

Three similar cases are described of an unusual combination of malignant lymphoma and extensive non-necrotic granulomas. The three patients presented with prominent splenomegaly without peripheral lymphadenopathy. They had normal or moderately elevated lymphocyte counts, abnormal lymphoid cells in the peripheral blood and bone marrow, and abnormalities of serum immunoglobulins. The lymphoid tumor was difficult to recognize but it was best identified in abdominal lymph nodes, it was composed of small atypical lymphocytes proliferating in a vaguely nodular pattern. The presence of multiple epithelioid granulomas obscured the neoplastic proliferation in the spleens and misled or delayed the final interpretation of the malignant disease. Abdominal lymph nodes and liver also contained granulomas although to a lesser extent. Studies of the lymphocyte surface characteristics in one patient suggested that the neoplasm derived from a monoclonal proliferation of B cells. The relationship between the exuberant epithelioid granulomas and the underlying neoplastic lymphoid proliferation is not clear. Regardless of whether it represents a distinct clinicopathological entity, recognition of this remarkable association has important practical implications since the lesions may be erroneously interpreted by the pathologist.     

Clinicopathologic features of neuroendocrine carcinomas of the stomach: appraisal of small cell and large cell variants

OBJECTIVE: To clarify the clinicopathologic features of neuroendocrine carcinomas (NECs) of the stomach, we reviewed 56 cases of surgically treated gastric carcinomas with a solid growth or with areas containing patterns characteristic for neuroendocrine (NE) tumors. METHODS: Of the 56 cases reviewed, we selected 33 cases of NEC based both on histologic patterns common to NE tumors and on histochemical/immunohistochemical results. RESULTS: The average age of patients with NEC was 69.8 years (range, 44-92 years). The majority of patients were men (male-female ratio, 23:10). The most frequently affected site was the upper third (46%) of the stomach. Grossly, 9 cases of NEC were fungating and 24 were ulcerated. As compared with 23 patients with non-NEC tumors, the patients with NECs had a worse prognosis. Histologically, NECs had a variety of histologic patterns, including solid, organoid, trabecular, pseudoglandular, spindle cell, and rosettelike. Based on both cell size and morphologic features, we subdivided NECs into 2 variants, namely, small cell NEC and large cell NEC. Our series included 12 cases of small cell NEC and 21 cases of large cell NEC. CONCLUSIONS: Compared with small cell NECs, large cell NECs had a higher mitotic count, larger polygonal cells, a lower nuclear-cytoplasmic ratio, coarser nuclear chromatin, and more frequent conspicuous nucleoli. Large cell NEC was an aggressive tumor with a very poor prognosis (median survival time, 15.2 months; 1-year survival rate, 58%), which approached that for small cell NEC.     

Subependymal giant cell astrocytoma: clinical, histologic and immunohistochemical characteristic of 3 cases

The role of 5-hydroxytryptamine (5-HT) in neural reflexes regulating secretion was examined in muscle-stripped segments of guinea-pig colon set up in modified flux chambers. A 15-microL pulse of 5-HT (100 microM) to the mucosal bath (1.5 mL), which was continuously perfused, evoked an increase in short-circuit current (Isc). The 5-HT-induced increase in Isc was inhibited by tetrodotoxin, N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan amide (5-HTP-DP), GR82334 and atropine, but not by tropisetron. 5-HTP-DP reduced the response to a 5-HT pulse over the concentration range of 1 nM to 1 microM. The Isc response to a 5-HT pulse was unaffected by the cyclooxygenase inhibitor, piroxicam. This contrasted with a reduction in the Isc response to mucosal stroking with a brush by piroxicam. The results suggest that a 5-HT pulse, like mucosal stroking, activates a secretory reflex that includes tachykinin and cholinergic neurons but, unlike mucosal stroking, does not release prostaglandins.