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Gastrointestinal stromal tumours (GISTs) are currently defined as mesenchymal tumours of the gastrointestinal tract that express KIT receptor tyrosine kinase. However, a small subgroup of tumours that fulfil the clinical and morphological criteria for GISTs lack KIT expression. So far, the biological features of these tumours have rarely been addressed. The present study describes seven gastrointestinal stromal neoplasms that presented clinicopathological features typical of GISTs but showed absence of CD117 expression as detected by immunohistochemistry. The tumours originated from the stomach (n = 5), duodenum (n = 1), and colon (n = 1), showing histologically either predominantly epithelioid (n = 3), mixed spindled and epithelioid (n = 2), or anaplastic/spindle cell (n = 2) type features. CD34 and alpha-smooth muscle actin (alpha-SMA) positivity was present in four and three tumours, respectively. Chromosomal analysis was performed in two cases, both showing losses of chromosomes 14, 22, and 1p, which is the characteristic feature of GISTs. Dual-colour interphase fluorescence in situ hybridization (FISH) analysis, utilizing chromosome 1p-, 14-, and 22-specific probes, revealed a similar cytogenetic profile in the remaining five tumour specimens. Mutational analysis of exons 9, 11, 13, and 17 of KIT, and exons 12 and 18 of PDGFRA was performed in all cases by denaturing high-pressure liquid chromatography (DHPLC) pre-screening, followed by direct sequencing. None of the tumours showed KIT mutant isoforms. Three tumours harboured PDGFRA exon 18 activating mutations; two were Asp --> Val(842) missense substitutions and one was a DIM842-844 amino acid deletion. KIT and PKC theta (protein activated in interstitial cells of Cajal and GISTs) expression was determined by western immunoblotting of the total cell lysates from three tumour biopsies. None of these three tumours expressed KIT, while all specimens showed expression of PKC theta protein. These findings indicate that there is a subgroup of KIT-negative GISTs that exhibit the same morphological, cytogenetic, and molecular features as KIT-positive tumours. While intragenic PDGFRA activating mutations are present in some of these tumours, the oncogenic events underlying the pathogenesis of the others remain unknown.

We present 3 cases of large B-cell lymphoma (LBCL) with a granular cytoplasmic staining for anaplastic lymphoma kinase (ALK). All of the cases showed striking similarities in morphology and immunohistochemical profile characterized by a massive monomorphic proliferation of CD20 ؊ /CD138 ؉ plasmablast-like cells. In one of the cases, initially diagnosed as a null-type anaplastic large cell lymphoma (ALCL), the B-cell phenotype became evident only at recurrence. Fluorescent in situ hybridization (FISH) and molecular studies led to the detection of a CLTC-ALK rearrangement in all 3 cases, without any evidence of full-length ALK receptor expression. The associated t(2;17)(p23;q23) was demonstrated in the karyotype of 2 cases. Although a similar CLTC-ALK aberration was previously identified in ALK-positive T-/null cell ALCL and inflammatory myofibroblastic tumor, its association with ALK-positive LBCL seems to be specific and intriguing.

Gastrointestinal stromal tumors (GISTs) comprise a biologically diverse group of neoplasms with respect to activating mutations in either KIT or PDGFRA, histology, anatomical site of origin, and clinical aggressiveness. In this study, we applied the high resolution array-based comparative genomic hybridization (array-CGH) technology to 66 primary GISTs (40 gastric and 26 nongastric, 48 with KIT and 18 with PDGFRA mutations) for identification of novel high-level alterations and for characterization of genotype-related genomic changes. All cases had genomic imbalances with the highest occurrence of 14q (73%), 1p (62%), 22q (59%), 15q (38%), and 13q (29%) losses. Our data indicate that loss of chromosome 14 and/or 22 is an early change in GIST tumorigenesis irrespective of tumor genotype. Furthermore, DNA copy number changes showed a site dependent pattern. These included lower incidence of losses at 14q (87% vs. 35%), and higher frequency of losses at 1p (45% vs. 85%) and 15q (17% vs. 69%) in nongastric versus gastric site (P<0.001 for all). However, in the multivariate analysis with adjustment to tumor risk stratification, only the 14q loss site-dependent pattern of distribution retained its significance. These findings suggest that loss of 14q is a relatively less frequent genetic event in the development of nongastric GISTs, the lack of which is most likely substituted by the accumulation of 1p/15q and other changes. The novel minimal overlapping regions of deletion at 1p (1p36.32-1p35.2, 1p34.1, and 1p22.1-1p21.3), 13q (13q14.11-q14.2 and 13q32.3-q33.1), and 15q23 were delineated, which point to chromosomal regions that may harbor genes relevant to the development of these neoplasms.

18, 15,19,20,22,24,25 trisomy 7, 19,20,22 and trisomy 12 15,18,19,20,22 genesis of these neoplasms.have been observed non-randomly but less frequently than Keywords: marginal zone B cell lymphoma; CGH; molecular trisomy 3. A t(11;18)(q21;q21) was found in three extranodal cytogenetics lymphomas 17,27 and structural aberrations of chromosome 1 recurrently involved the chromosomal regions 1p22, 15,19 1p34 22,25 and 1q21. 22 IntroductionThe distinct nature of MZBCL is further underlined by the fact that known lymphoma-associated chromosomal transMarginal zone B cell lymphoma (MZBCL) represents a distinct locations or rearrangements of the BCL1, BCL2, BCL3 and subtype of B cell non-Hodgkin's lymphoma (NHL), which BCL6 oncogenes have not been detected in these lymincludes lymphoma of the mucosa-associated lymphoid tissue phomas. 3,16,17,22,28,29 Rearrangements of CMYC and biallelic (MALT lymphoma), 1 monocytoid B cell lymphoma, 2 and inactivation of P53 have been associated with high-grade splenic MZBCL. 3 So far, little is known about pathogenesis, transformation of gastric MALT lymphomas. 30,31 biology, and natural history of MZBCL, in part due to the fact In the present study, 25 histologically and immunophenothat these lymphomas are relatively rare and have only typically well characterized cases of extranodal, nodal, and recently been recognized and defined as a disease entity. 4 splenic MZBCL were investigated with the recently developed The morphologic appearance is rather heterogeneous and technique of CGH. 32 CGH is a double color hybridization characterized by a mixture of centrocyte-like cells, small lymprocedure, which provides in a single experiment an overview phocytes, monocytoid B cells, plasma cells, and larger blastof genomic imbalances, such as partial or complete trisomies, monosomies, or amplifications within the tumor genome. In responsibility is assumed by its authors.