Comparison of germinal center markers CD10, BCL6 and human germinal center-associated lymphoma (HGAL) in follicular lymphomas.

BACKGROUND: Recently, human germinal center-associated lymphoma (HGAL) gene protein has been proposed as an adjunctive follicular marker to CD10 and BCL6. METHODS: Our aim was to evaluate immunoreactivity for HGAL in 82 cases of follicular lymphomas (FLs)--67 nodal, 5 cutaneous and 10 transformed--which were all analysed histologically, by immunohistochemistry and PCR. RESULTS: Immunostaining for HGAL was more frequently positive (97.6%) than that for BCL6 (92.7%) and CD10 (90.2%) in FLs; the cases negative for bcl6 and/or for CD10 were all positive for HGAL, whereas the two cases negative for HGAL were positive with BCL6; no difference in HGAL immunostaining was found among different malignant subtypes or grades. CONCLUSIONS: Therefore, HGAL can be used in the immunostaining of FLs as the most sensitive germinal center (GC)-marker; when applied alone, it would half the immunostaining costs, reserving the use of the other two markers only to HGAL-negative cases.

Immunostaining for nucleophosmin in bone marrow trephine biopsy specimens in acute myeloid leukemias.

OBJECTIVE: To evaluate the technicalfeasibility of nucleophosmin (NPM) staining and the problems of interpretations by pathologists in an academic regional hospital in Italy. STUDY DESIGN: Acute myeloid leukemia (AML) is a heterogeneous clonal disorder of hematopoietic progenitor cells that presents genetic abnormalities in several genes, including NPM. Mutations of the NPM gene occur in 35% of patients with AML with normal karyotype, causing cytoplasmic rather than nuclear localization of the protein. Because the NPM antibody recently became commercially available, we immunostained a series of diagnosed AML samples. We performed NPM immunostaining in 48 AML cases. NPM immunostaining was correlated with phenotypic and cytogenetic data. RESULTS: Reactivity for NPM was exclusively nuclear in 31 cases (64.6%) and nuclear and cytoplasmic in 17 cases (35.4%). The distribution of NPM cytoplasmic staining was more frequently observed in cases with monocytic differentiation and with normal karyotype or with minor cytogenetic abnormalities (p < 0.05). CONCLUSION: NPM immunostaining is a feasible test, without problems of interpretation for pathologists, when the sections are optimally prepared and can be considered predictive of peculiar phenotypic and karyotype subtypes of AML, in addition to the well-known prognostic role.

Lesional skin chemokine CTACK/CCL27 expression in mycosis fungoides and disease control by IFN-alpha and PUVA therapy.

Recruitment of neoplastic T cells to skin is a critical step in the pathogenesis of mycosis fungoides (MF) lesions. Cutaneous T-cell attracting chemokine (CTACK)/CCL27 attracts memory T cells to skin, resulting in increased cutaneous expression. The interactions between neoplastic cells and skin immune system require further elucidation. CTACK/CCL27 expression and density of dendritic cells (DC), CD8+ and CD4+ lymphocytes were investigated in skin lesions of 52 early-stage MF patients treated by interferon (IFN)-alpha in combination with photochemotherapy (psoralen plus ultraviolet A, PUVA). Skin lesion biopsies obtained at diagnosis and after treatment were studied by immunohistochemistry. Initial CTACK/CCL27 expression was abnormal/suprabasal in 36 patients. Normal/basal CTACK/CCL27 expression tended to correlate with a high DC density and low CD4+ cell density in the neoplastic infiltrate. Treatment induced a significant increase in CTACK/CCL27 expression (chi(2) test: P=0.004). Overall, 33 patients relapsed [median event-free survival (EFS), 46 months] during follow-up (median, 92.5 months, range, 43-165). Normal/basal CTACK/CCL27 expression at the end of treatment correlated with lower rates of recurrence and a longer median EFS (111 months vs. 39 months with suprabasal expression; log rank test: P=0.031). CTACK/CCL27 overexpression in early-stage MF might thus be related to a balance between neoplastic cells and immunomodulant DC. Normal CTACK/CCL27 expression after treatment designates a subset of patients with favorable disease behavior. The mechanisms underpinning CTACK/CCL27 overexpression after therapy in the remaining patients, who are at greater risk of recurrence, warrant further investigation.

Diffuse large B-cell lymphoma with Homer-Wright rosettes, sinusoidal growth pattern, and CD30 expression: a possible overlap between microvillous lymphomas and sinusoidal CD30-positive large B-cell lymphomas.

Rosette formation is an unusual finding in malignant lymphomas. We herein report another case of a diffuse large B-cell lymphoma (DLBCL) with ultrastructural evidence of cellular projections, sinusoidal growth pattern, and strong CD30 expression. A literature review of the DLBCL cases showing all these features was also performed.

Gastrointestinal stromal tumor. A study of 158 cases: clinicopathological features and prognostic factors.

OBJECTIVE: To increase knowledge on the behavior of gastrointestinal stromal tumors (GISTs) and factors influencing therapy. STUDY DESIGN: The clinicomorphological features of 158 GISTs were analyzed. Survival analysis was performed on the whole series, as well as on a selected group of patients with high risk GIST who did not receive imatinib mesylate. The impact of imatinib mesylate on the prognosis was investigated. RESULTS: Most of the GISTs had a benign behavior. The risk class was a powerful prognostic factor but was unable to predict the outcome in a single case; even patients in the high risk class not receiving imatinib mesylate had a low mortality rate. In this group, it was the mitotic activity that better correlated with prognosis, and a cut point of 10 mitoses per 50 high-power field can be fixed to discriminate cases with favorable or unfavorable outcome. Patients with GISTs presenting as aggressive disease received great benefit from imatinib mesylate therapy. CONCLUSION: Mitotic activity is important in predicting the outcome of patients with high risk GIST who present at diagnosis without dissemination. This finding can have therapeutic implications.

The G/A nucleotide change at cDNA position 2494 in the E-cadherin gene (CDH1): analysis in Italian patients.

Current studies are investigating new E-cadherin gene (CDH1) mutations that may be responsible for diffuse gastric cancer susceptibility. Recently, a novel CDH1 germline variant presenting a G/A nucleotide change at cDNA position 2494 has been found in Japanese patients with familial diffuse gastric cancer. The consequent amino acid variation (Val/Met) may alter the binding activity to beta-catenin and the adhesive function of the E-cadherin protein. We have investigated its frequency in Italian cases of sporadic diffuse gastric cancer a well as in healthy controls. Peripheral blood samples were collected from consecutive patients with sporadic, diffuse gastric cancer and from healthy controls in the District of Urbino, Marche Region, Central Italy. After DNA extraction, standard techniques for molecular analyses were used to investigate the 2494 G/A germline nucleotide change in CDH1 cDNA. None of the 48 patients and 48 controls showed the G/A 2494 nucleotide change. Assuming a binomial distribution of the mutation among individuals and the absence of mutations in the 48 patients, the 95% upper bound for the underlying mutation frequency was 7.4%. The novel CDH1 nucleotide change is uncommon in Italian patients with sporadic diffuse gastric cancer. Given these results, further analyses in large population-based studies are not advisable.