Although immunohistochemistry is routinely performed by many pathology laboratories, its standardization still lags behind. A major cause of variation in the reproducibility of immunohistochemical staining is induced by tissue fixation and, to a lesser degree, tissue processing. This report, stemming from the first meeting of the International Consensus Group on Standardization and Quality Control (ICGSQC) in Nice, France, summarizes the problem and suggests solutions to begin to achieve standardization of fixation and processing. Most laboratories use neutral-buffered formalin (10%) for tissue fixation which introduces cross-links, whereas coagulative fixatives are less popular. Problems with formalin fixation comprise delay of fixation and variations in the duration of the fixation mainly. Solutions to these problems could be to start fixation soon (<30 min) after surgical removal of the tissue and to avoid overfixation (>24-48 hrs). For tissue processing, the most important problem is inadequate tissue dehydration prior to paraffin embedding. This can be prevented by preparing all solutions freshly every week, depending on the volume of tissue processed. If consistently applied, these procedures could eliminate some of the sources of variation in immunohistochemical stains.

Although several recurrent genetic aberrations are known to occur in MALT lymphoma, no comprehensive study on the most prevalent MALT lymphoma-associated genetic aberrations is available. We therefore screened 252 primary MALT lymphomas for translocations t(11;18)(q21;q21), t(14;18) (q32;q21), and t(1;14)(p22;q32), and trisomies 3 and 18. The above-listed translocations occurred mutually exclusively and were detected overall in 13.5, 10.8, and 1.6% of the cases; trisomy 3 and/or 18 occurred in 42.1%. The frequency at which the translocations occurred varied markedly with the primary site of disease. The t(11;18)(q21;q21) was mainly detected in pulmonary and gastric tumors, whereas the t(14;18)(q32;q21) was most commonly found in lesions of the ocular adnexa/ orbit, skin, and salivary glands. Trisomies 3 and 18 each occurred most frequently in intestinal and salivary gland MALT lymphomas. Our results demonstrate that the three translocations and trisomies 3 and 18 occur at markedly variable frequencies in MALT lymphoma of different sites.

T(11;18)(q21;q21) is the most common structural abnormality in extranodal marginal zone B-cell lymphoma of mucosaassociated lymphoid tissue (MALT lymphoma) leading to the fusion of the apoptosis inhibitor-2 (API2) gene and the MALT lymphoma-associated translocation (MALT1) gene. In 2 patients with MALT lymphoma of the liver and skin, respectively, t(14;18)(q32;q21) was observed by cytogenetic analysis. Subsequent fluorescence in situ hybridization (FISH) studies disclosed that the immunoglobulin heavy-chain locus (IGH) and the MALT1 gene were rearranged by this translocation. In order to screen a large series of MALT lymphomas for this aberration, a 2-color interphase FISH assay was established. Among a total of 66 cases, t(14;18)(q32;q21) involving IGH and MALT1 was detected in MALT lymphomas of the liver (4 of 4), skin (3 of 11), ocular adnexa (3 of 8), and salivary gland (2 of 11), but did not occur in MALT lymphomas of the stomach (n ‫؍‬ 10), intestine (n ‫؍‬ 9), lung (n ‫؍‬ 7), thyroid (n ‫؍‬ 4), or breast (n ‫؍‬ 2). In total, 12 of 66 (18%) MALT lymphomas harbored t(14;18)(q32; q21); 7 additional cases of splenic marginal zone lymphoma tested negative. All of the 12 MALT lymphomas featuring the t(14;18)(q32;q21) were negative for t(11; 18)(q21;q21) by reverse transcriptasepolymerase chain reaction (RT-PCR). However, trisomy 3 and/or 18 was found in 4 of 12 cases, suggesting that the t(14;18)(q32;q21) does not occur as the sole genetic abnormality. This study identifies IGH as a new translocation partner of MALT1 in MALT lymphomas, which tend to arise frequently at sites other than the gastrointestinal tract and lung. In contrast to t(11;18)(q21;q21) ؉ MALT lymphomas, those with t(14;18)(q32;q21) may harbor additional genetic abnormalities.