| Objective:To evaluate morphological features and expression of BCL10,CARMA1 and NF-.B proteins,also detect several specific genetic aberrations,ie, t(11;14)(q21;q21);t(1;14)(p22;q32);t(14;18)(q32;q21) and some other genetic abnormalities in extranodal marginal zone B cell lymphomas of mucosa-associated lymphoid tissue(MALT lymphoma) arising from different anatomical sites.Methods:(1) 217 MALT lymphomas from different sites were collected for morphological evaluation.Among those cases,60 cases were from ocular adnexa,47 from stomach,25 from salivary gland,23 from lung,20 from intestine,17 from skin, 8 from liver,6 from thyroid,and 11 from other sites(3 from larynx and throat,2 from epididymis,2 from latter tongue,1 from thymus,gum,pancreas and kidney, respectively).Histological features evaluated according to HE sections.(2) Genetic detection studied by interphase fluorescent in situ hybridization(FISH) on 217 formalin-fixed,paraffin-embedded tissues.API2-MALT1 dual color fusion probe, BCL10,IgH and MALT1 dual color split probes were available to detect above mentioned genetic aberrations.API2-MALT1 fusion probe also was used in 32 diffuse large B cell lymphomas(DLBCL) for comparison.(3) Immunohistochemistry was used to dectect BCL10,CARMA1 and NF-.B proteins in lymphoid reactive lesions of 10 tonsil and 5 lymph nodes;BCL10 also used in 217 MALT lymphomas and 143 non-MALT,non-Hodgkin's lymphomas(NHL),CARMA1 and NF-.B just performed in 74 MALT lymphomas.Results:Part one:(1) In this group,MALT lymphomas mainly occurred on the people in 55 years or so,the mean age was 52.4 and median age was 53.Male were predominant and the ratio for male and female is 1.5:1.(2) Under the low magnification,MALT lymphomas often showed nodular pattern,and could divide into 4 different style.Based on with or without residual germinal center,nodules showed enlarged marginal zone type and solid nodule type;with lymphoma progression, nodules could become diffuse type and transformation with more or less blastoid large cells.(3) In MALT lymphomas cellular types were various.Those different cells could be seen simultaneously in a lesion,but more often,in a lesion it showed predominantly in a special cellular type.But cluster of monocytoid B cells and plasma cells with mounts of nuclear inclusions may imply malignant nature in some anatomical sites.(4) MALT lymphomas always connected with chronic inflammations. In a lesion the tumor and inflammation could juxtapose or with transformation.If cells showed distinct infiltration,such as destroyed the blood wall,infiltrate the nerve fiber,epithelium,or rooted in the deeper tissues,in a proper context cellular characters and sites,may help for a diagnosis of malignancy.Part two:(1) In the lymphoid reactive lesions,the expression pattern of BCL10,CARMA1 and NF-.B was similar,which all expressed in the B cell cytoplasm of germinal center,whereas the interfollicle cells were weak expression.(2) BCL10 was commonly expressed in NHL.In MALT lymphomas,78 of 217(35.9%) showed nuclear expression.Whereas in the other type NHL rather than MALT lymphomas,except 3 mucosa DLBCL showed nuclear expression,the rest of all cases were cytoplasmic expression or negative.(3) To MALT lymphomas from different sites,the rate of nuclear BCL10 expression is various.It could be seen in 12 of 20 intestinal,10 of 23 pulmonary,26 of 60 ocular adnexal,3 of 8 hepatic,17 of 47 gastric,5 of 17 cutaneous,1 of 6 thyroid and 1 of 25 salivary gland MALT lymphomas.(4) In MALT lymphomas most cases showed cytoplasmic expression of CARMA1(77.0%,57/74),few cases were nuclear expression(8.1%,6/74).But there was no statistical relation between nuclear BCL10 and CARMA1 expression(P=0.076).(5) NF-.B/P65 in 35 of 74(47.3%) MALT lymphomas were cytoplasmic expression,39 of 74(52.7%) were nuclear and cytoplasmic expression simultaneously.In statistical analysis it showed that BCL10 nuclear expression was close connected with NF-.B/P65 nuclear expression(P＜0.001),but CARMA1 expression in nucleus or cytoplasm did not show any connection with NF-.B/P65 nuclear expression(P＞0.05).Part three:(1) In 217 MALT lymphomas,API2-MALT1 fusion gene was found in 26 cases(12.0%).The positive cases were seen in 9 of 23(39.1%) pulmonary,10 of 40(25.0%) gastric which did not have large cell transformation,3 of 25(12.0%) salivary gland,2 of 20 (10.0%) intestinal,and 2 of 60(3.3%) ocular adnexal MALT lymphomas.In 7 gastric MALT lymphomas with high grade transformation and all from skin,thyroid,liver and other sporadic sites did not find API2-MALT1 fusion gene.In 32 DLBCL from gastrointestinal tract did not find API2-MALT1 either.(2) In a pulmonary MALT lymphoma it showed abnormal IgH and MALT1 gene signals,may be t(14;18);6 cases(2 salivary gland,2 liver,1 stomach with high grade components and 1 thyroid) showed three signals of MALT1 gene,may be trisomy 18;3 cases(1 stomach,1 intestine and 1 stomach with high grade components) showed cluster MALT1 gene signals,may be MALT1 gene amplification.(3) 3 cases(2 stomach and 1 lung) showed abnormal IgH and BCL10 signals simultaneously,may be t(1;14).Conclusion:part one:(1) MALT lymphomas were a group of low grade extranodal B cell lymphomas that ordinarily occurred in the middle to aged people.But in the different sites,it's diversified on the average age,the ratio of male to female,and the predominant cellular morphology.Compared with the information of International Lymphoma Study Group(ILSG),in our group the average age is eight years or so younger than that in the former,and male is predominant.(2) MALT lymphomas often form a complicated cellular background,and appeared similar with reactive or inflammatory lesions.In fact,for some cases,lymphomas often juxtapose with benign lesion or overlapped each other.As a result,differentiation with the inflammatory lesions is the most important problem for clinicopathologists.Some morphological characteristics are useful for diagnosis.Part two:(1) Immunohistochemistry(IHC) showed that parts of MALT lymphomas expressed BCL10 in nucleus.Compared with other types of NHL,except few gastric DLBCL showed nuclear BCL10 expression, most NHL just showed cytoplasmic BCL10 expression.This phenomena suggests that BCL10 aberrant nuclear expression may helpful for diagnosis of MALT lymphomas, especially for the pulmonary and ocular adnexal MALT lymphomas.(2) On the statistical analysis,nuclear BCL10 expression was related with NF-.B nuclear expression.Because NF-.B nuclear expression is the hallmark of cellular activation, so BCL10 nuclear expression suggests that aberrant BCL10 may trigger cellular activation and is the important factor for tumor genesis.(3) The cytoplasmic signaling molecule CARMA1 also could express on the nucleus,but the detailed mechanism and clinical significance are not clear.But compared with NF-.B and BCL10 nuclear expression,CARMA1 cytoplasmic or nuclear expression is independent and not related with former.Part three:(1) t(11;18) is the most common genetic abnormality.On the contrary,t(1;14) and t(14;18) were pretty rare. On the whole,genetic abnormalities are not common in MALT lymphomas.Genetic examination can not be a useful tool for clinical diagnosis.(2) t(11,18) is a specific genetic aberration for low-grade MALT lymphomas,and did not see in DLBCL.This phenomena support that MALT lymphoma with t(11;18) would not transform into DLBCL.(3) Pulmonary MALT lymphomas have the highest incidence for genetic aberration.As a result,FISH is a useful tool for diagnosis of pulmonary lymphoid reactive lesions,especially for small biopsy.(4) MALT1 gene amplification may occur in MALT lymphomas.(5) BCL10 nuclear expression is not related with genetic aberrations,IHC for BCL10 can not forecast genetic events.
|
PDF Full Text Request