Polymerase chain reaction (PCR) assessment of clonal immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements is an important diagnostic tool in mature B-cell neoplasms. However, lack of standardized PCR protocols resulting in a high level of false negativity has hampered comparability of data in previous clonality studies. In order to address these problems, 22 European laboratories investigated the Ig/TCR rearrangement patterns as well as t(14;18) and t(11;14) translocations of 369 B-cell malignancies belonging to five WHO-defined entities using the standardized BIOMED-2 multiplex PCR tubes accompanied by international pathology panel review. B-cell clonality was detected by combined use of the IGH and IGK multiplex PCR assays in all 260 definitive cases of B-cell chronic lymphocytic leukemia (n ¼ 56), mantle cell lymphoma (n ¼ 54), marginal zone lymphoma (n ¼ 41) and follicular lymphoma (n ¼ 109). Two of 109 cases of diffuse large B-cell lymphoma showed no detectable clonal marker. The use of these techniques to assign cell lineage should be treated with caution as additional clonal TCR gene rearrangements were frequently detected in all disease categories. Our study indicates that the BIOMED-2 multiplex PCR assays provide a powerful strategy for clonality assessment in B-cell malignancies resulting in high Ig clonality detection rates particularly when IGH and IGK strategies are combined.

Polymerase chain reaction (PCR) assessment of clonal T-cell receptor (TCR) and immunoglobulin (Ig) gene rearrangements is an important diagnostic tool in mature T-cell neoplasms. However, lack of standardized primers and PCR protocols has hampered comparability of data in previous clonality studies. To obtain reference values for Ig/TCR rearrangement patterns, 19 European laboratories investigated 188 T-cell malignancies belonging to five World Health Organization-defined entities. The TCR/Ig spectrum of each sample was analyzed in duplicate in two different laboratories using the standardized BIOMED-2 PCR multiplex tubes accompanied by international pathology panel review. TCR clonality was detected in 99% (143/145) of all definite cases of T-cell prolymphocytic leukemia, T-cell large granular lymphocytic leukemia, peripheral T-cell lymphoma (unspecified) and angioimmunoblastic T-cell lymphoma (AILT), whereas nine of 43 anaplastic large cell lymphomas did not show clonal TCR rearrangements. Combined use of TCRB and TCRG genes revealed two or more clonal signals in 95% of all TCR clonal cases. Ig clonality was mostly restricted to AILT. Our study indicates that the BIOMED-2 multiplex PCR tubes provide a powerful strategy for clonality assessment in T-cell malignancies assisting the firm diagnosis of T-cell neoplasms. The detected TCR gene rearrangements can also be used as PCR targets for monitoring of minimal residual disease.

Various patterns of Epstein-Barr virus (EBV)-associated B-cell lymphoproliferation occur in patients with immunodeficiency. We studied 17 cases of T-cell lymphoma displaying extensive EBV-driven B-cell lymphoproliferation or simultaneous/subsequent EBV-associated B-cell lymphoma. In 10 cases of angioimmunoblastic T-cell lymphoma, an uncommonly prominent population of EBV+ atypical, activated, focally confluent large transformed B cells was found in the background of T-cell lymphoma. In 4 cases, an EBV-associated B-cell neoplasm (3 diffuse large B-cell lymphomas, 1 plasmacytoma) occurred in patients with T-cell lymphoma. Three cases were composite lymphomas of a peripheral T-cell lymphoma, unspecified, combined with EBV-associated diffuse large B-cell lymphoma. The transformed B-cell population displayed EBV latency types 2 and 3. Monoclonal and oligoclonal B-cell populations were detected in 5 and 6 cases, respectively. Similar to other states of immunodeficiency, disease-related and therapy-induced immunosuppression in T-cell lymphoma may lead to a prominent EBV-associated B-cell lymphoproliferation and to EBV+ B-cell neoplasms.

Differentiation of small and atypical hemangiomas from other hepatic masses using imaging methods can be difficult, especially in patients with underlying malignant disease. Therefore, contrast-enhanced ultrasound was assessed in patients with histologically confirmed hemangiomas with respect to contrast-enhancing kinetics and tumor characteristics. In 58 patients with indeterminate hepatic lesions demonstrated with at least 2 imaging methods (ultrasound/computed tomography/magnetic resonance imaging), ultrasound-guided liver biopsy revealed hemangioma. In all patients a hepatic neoplasm had been suspected because of underlying malignant disease (n ‫؍‬ 41), liver cirrhosis (n ‫؍‬ 15), or growth of the lesion (n ‫؍‬ 2). All patients underwent nonlinear, low mechanical index real-time contrast-enhanced ultrasound scanning with bolus injections of SonoVue. Peripheral nodular arterial enhancement was detected in 43 patients (74%), whereas the typical metastatic peripheral rim-like enhancement was not observed at all. Strong homogenous arterial enhancement was found in 9 of 58 (16%) patients. In 6 patients (10%), the arterial contrast enhancement pattern could not be determined because of the very small size of the lesions or fibrotic nodules. Forty-five (78%) of the hemangiomas showed homogenous centripetal filling within 180 seconds. Conclusion: Contrast-enhanced ultrasound demonstrates typical hemangioma imaging characteristics, that is, peripheral nodular contrast enhancement and iris-diaphragm sign in a high percentage of patients with undetermined lesions. This technique may therefore improve noninvasive functional characterization and differentiation of hemangiomas. (HEPATOLOGY 2007;45:1139-1145

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