Cytogenetic study of malignant triton tumor: a case report

Malignant triton tumor (MTT) is a highly malignant neoplasm, classified as a variant of malignant peripheral nerve sheath tumor (MPNST) with rhabdomyoblastic differentiation. Few cytogenetic studies of MTT have been reported using conventional cytogenetic analysis. Here, we report a comprehensive cytogenetic study of a case of MTT using G-banding, Spectral Karyotyping(), and fluorescence in situ hybridization (FISH) for specific regions. A complex hyperdiploid karyotype with multiple unbalanced translocations was observed: 48 approximately 55,XY,der(7)add(7)(p?)dup(7)[2],der(7) t(7;20)(p22;?)ins(20;19)[5],der(7)ins(8;7)(?;p22q36)t(3;8)t(8;20)[15],-8[5],-8[19],r(8)dup(8), +der(8)r(8;22)[4],-9[9],der(11)t(11;20)(p15;?)ins(20;19)[22],der(12)t(8;12)(q21;p13)[21],der(13) t(3;13)(q25;p11),-17,-19,der(19)t(17;19)(q11.2;q13.1),-20,-22,+4 approximately 7r[cp24]/46,XY[13]. The 1995 International System for Human Cytogenetic Nomenclature was followed where possible. Note that breakpoints were frequently omitted where only SKY information was known for a small part of an involved chromosome. Our analysis revealed some breakpoints in common with those previously reported in MTT, MPNST, and rhabdomyosarcoma, namely 7p22, 7q36, 11p15, 12p13, 13p11.2, 17q11.2, and 19q13.1. FISH showed high increase of copy number for MYC and loss of a single copy for TP53.     

A cytogenetic analysis of 2 cases of phosphaturic mesenchymal tumor of mixed connective tissue type

Phosphaturic mesenchymal tumor of mixed connective tissue type is a rare, histologically distinctive mesenchymal neoplasm associated with tumor-induced osteomalacia resulting from production of the phosphaturic hormone fibroblast growth factor 23. Because of its rarity, specific genetic alterations that contribute to the pathogenesis of these tumors have yet to be elucidated. Herein, we report the abnormal karyotypes from 2 cases of confirmed phosphaturic mesenchymal tumor of mixed connective tissue type. G-banded analysis demonstrated the first tumor to have a karyotype of 46,Y,t(X;3;14)(q13;p25;q21)[15]/46XY[5], and the second tumor to have a karyotype of 46, XY,add(2)(q31),add(4)(q31.1)[2]/92,slx2[3]/46,sl,der(2)t(2;4)(q14.2;p14),der(4)t(2;4)(q14.2;p14),add(4)(q31.1)[10]/46,sdl,add(13)(q34)[4]/92,sdl2x2[1]. These represent what is, to our knowledge, the first examples of abnormal karyotypes obtained from phosphaturic mesenchymal tumor of mixed connective tissue type.     

Karyotypic findings in two cases of male breast cancer

Male breast cancer is uncommon; so far, only 10 cases with chromosome banding analysis have been published. We report the cytogenetic findings of two invasive breast cancers in two Caucasian men lacking a history of familial breast cancer and more than 70 years of age. Both had ductal carcinomas with lymphangiosis carcinomatosa and positive lymph nodes at diagnosis. Strong expression of estrogen receptor, weak expression of progesterone receptor, and lack of expression of androgen receptor by both tumors were demonstrated by immunohistochemistry, as well as lack of expression of p53 and C-ERB-B-2. The karyotypes were 45 approximately 46,XY,-Y[4],-7[2],+8[2],t(8;12)(q21;q24)[3], del(9)(q22)[3],del(11)(p11p14)[5],del(18)(q21)[7], t(19;20)(p10;q10)[8] [cp13] and 61 approximately 69,XXXY,-Y[3], del(2)(p21)[4],del(3)(p22q26)[3],-4,-4[5],+5,+5[5], dic(5;11)(p14;q23)[3],del(6)(q23)[4],del(8)(p21)[3],-9[4],-11[4],+ i(12)(p10)[4],-16[3],del(17)([13)[5],del(18)(q21)[4],+19[5], +20[4][cp7], respectively. Although the available data on male breast cancer are still very limited, our findings confirm that gain of an X chromosome, loss of the Y chromosome, gain of chromosome 5, and loss of material from chromosomes 17 and 18 are nonrandom aberrations in male breast cancer. Trisomy 8, characteristic of ductal carcinomas, was found in one case.     

Therapy-related acute leukemia with mixed phenotype and t(9;22)(q32;q11.2): a case report and review of the literature

Therapy-related acute leukemia showing mixed phenotype is extremely rare. We report a 49-year-old woman who presented with palpable masses in her neck and back. She had received systemic chemotherapy (adriamycin and cisplatin) and radiotherapy for endometrial adenocarcinoma 7 years before. Her peripheral blood and bone marrow showed increased blasts, which coexpressed myeloid (CD13, CD33, and myeloperoxidase) and B-lymphoid antigens (CD19 and CD79a). Cytogenetic analysis showed a karyotype of 46,XX,dup(1)(q21q32),add(5)(q33),t(9;22)(q34;q11.2)[12]/47,idem,+der(22)t(9;22)[8], and BCR/ABL1 rearrangement was detected. Leukemic infiltration was also confirmed in her back mass. After induction chemotherapy with idarubicin, cytarabine, and imatinib, she achieved complete remission. Only 2 cases of therapy-related acute leukemia with mixed phenotype have been reported so far: one with hyperploidy and the other with t(1;21)(p36;q22). To the best of our knowledge, this is the first case of therapy-related acute leukemia with mixed phenotype and t(9;22) as well as extramedullary leukemic infiltrations.     

Therapy-related, mixed phenotype acute leukemia with t(1;21)(p36;q22) and RUNX1 rearrangement

We describe here a new case of therapy-related acute leukemia with t(1;21)(p36;q22). A 25-year-old man was admitted because of anemia and thrombocytopenia. Four years before, he had received combination chemotherapy including etoposide for seminoma. Bone marrow was hypercellular, with 49% myeloperoxidase (MPO) staining-negative blasts. Chromosome analysis showed 46,XY,t(1;21)(p36.3;q22)[11]/49,sl,+8,+16,+20[9]. Fluorescence in situ hybridization demonstrated that RUNX1 signals at 21q22 were split onto the der(1)t(1;21) and der(21)t(1;21). Immunophenotypic analyses revealed that blasts were positive for CD19, CD79a, and cytCD22, as well as MPO, CD13, and CD33, fulfilling the diagnostic criteria of mixed phenotype acute leukemia, B/myeloid. The patient died of disease progression after 10 months. Thus, acute leukemia with t(1;21) and RUNX1 rearrangement could be associated with B/myeloid mixed phenotype as well as previous topoisomerase II inhibitor therapy and poor prognoses.     

Tandem duplication mosaicism: characterization of a mosaic dup(5q) and review

Mosaicism for tandem duplications is rare. Most patients reported had abnormal phenotypes of varying severity, depending on the chromosomal imbalance involved and the level of mosaicism. Post-zygotic unequal sister-chromatid exchange has been proposed as the main mechanism for tandem duplication mosaicism. However, previous molecular analyses have implicated both meiotic and post-zygotic origins for the duplication. We describe a newborn male who was originally diagnosed in utero with arrhythmia and tetralogy of Fallot. He had multiple dysmorphic features including telecanthus, blepharophimosis, high broad nasal bridge with a square-shaped nose, flat philtrum, thin upper lip, down-turned corners of the mouth, high-arched palate, micrognathia, asymmetric ears, and long, thin fingers and toes. Karyotyping of peripheral blood lymphocytes showed mosaicism for a tandem duplication of part of the long arm of one chromosome 5: mos46,XY,dup(5)(q13q33)[6]/46,XY[45]. Fibroblast cultures had the same mosaic karyotype with a higher frequency of the dup(5) clone: mos46,XY,dup(5)(q13q33)[9]/46,XY[21]. Fluorescence in situ hybridization analysis with a wcp5 confirmed the chromosome 5 origin of the additional material. Parental karyotypes were normal indicating a de novo origin of the dup(5) in the proband. Molecular analyses of chromosome 5 sequence-tagged-site (STS) markers in our family were consistent with a post-zygotic origin for the duplication. Therefore, mosaicism for tandem duplications can arise both through meiotic or mitotic errors, as a result of unequal crossing over or unequal sister-chromatid exchange, respectively. Our review indicates that mosaicism for tandem duplications is likely under-ascertained and that parental karyotyping of probands with non-mosaic tandem duplications should be performed.     

Angiomyxolipoma shares cytogenetic changes with lipoma, spindle cell/pleomorphic lipoma and myxoma

Angiomyxolipoma is a rare variant of lipoma, two cases of which have recently been described. We report on the hitherto unreported clonal chromosomal changes of a third case of angiomyxolipoma. The karyotype showed a 46,XX,t(7;13)(p15;q14),t(8;12)(q13;p13)[17]/46,XX[3]. The involvement of 13q14, 12p13, and 8q13 supports a relationship with other types of benign lipomatous and myxoid tumors.     

Three rearrangements of chromosome 5 in a patient with myelodysplastic syndrome: an atypical deletion 5q, a complex intrachromosomal rearrangement of chromosome 5, and a paracentric inversion of chromosome 5

We report the case of a 74-year-old man who sought care for de novo myelodysplastic syndrome (RAEB-1). Conventional cytogenetic techniques showed a karyotype with two different deletions of the long arm of chromosome 5 distributed in three clones: 46,XY,del(1)(p34),del(5)(q14q23)[2]/46,XY,del(1)(p34),del(5)(q14q34)[10]/46,idem,inv(5)(q?11q?34)[7]. Precise characterization of the breakpoints, delineation of the deleted regions, identification of the complex intrachromosomal rearrangement of chromosome 5, and sequential accumulation of chromosomal abnormalities were elucidated by several fluorescence in situ hybridization analyses. We also assessed the clinical, biological, and cytogenetic evolution under lenalidomide treatment and after its interruption.     

Multiplex ligation-dependent probe amplification (MLPA) screening in meningioma

The results of cytogenetic analysis of a solitary fibrous tumor (SFT) of the oral cavity in a 43-year-old man is reported. The abnormal cells carried a complex translocation with the karyotype 46,XY [15 cells]/46,XYt(1;17;18)(p13;q11.2;q21)[5 cells]. This is the first case reporting chromosomal aberrations in an oral SFT.     

Imatinib resistance in a novel translocation der(17)t(1;17)(q25;p13) with loss of TP53 but without BCR/ABL kinase domain mutation in chronic myelogenous leukemia

We describe here two novel translocations, t(7;14)(p22;q13) and der(17)t(1;17)(q25;p13), in a 41-year-old man with an accelerated phase (AP) of chronic myelogenous leukemia (CML). Chromosome analysis initially showed 46,XY,t(7;14)(p13;q22),t(9;22)(q34;q11.2)[20]. In 3 years, the karyotype evolved to 45,X,−Y,der(7)t(7;14)(p13;q22),t(9;22)(q34;q11.2),−14,der(17)t(1;17)(q25;p13),+der(22)t(9;22)[20], accompanied with a resistance to imatinib mesylate. The TP53 was deleted from the der(17)t(1;17)(q25;p13), but there was no mutation of TP53 in the remaining allele. Mutations in the BCR/ABL kinase domain could not be detected as well. Morphologically, dysplastic changes including pseudo-Pelger–Huët anomaly appeared in the bone marrow cells. These findings suggest that the t(7;14)(p22;q13) translocation had a crucial role in the progression to CML-AP, and that the resistance to imatinib may be due to the additional cytogenetic abnormalities, including der(17)t(1;17)(q25;p13), but not to BCR/ABL mutations.     

Complex karyotypic changes, including rearrangements of 12q13 and 14q24, in two leiomyosarcomas

Cytogenetic investigation of short-term cultures from two leiomyosarcomas revealed complex karyotypic changes in both cases. The first tumor, a subcutaneous leiomyosarcoma of the knee, had the karyotype 70-80,XY, +X, +Y, +1, +1, +2, +2, +3, +3, +4, +4, +7, +7, +8, +8, +9, +10, +15, +15, +16, +16, +18, +19, +20, +21, +21, +22, +22,t(?;5)(5;21)(?;q35p11;q11), t(?;5)(5;21)(?;q35p11;q11), +del(11)(q22),der(13)t(12;13)(q13;q22),der(14)t(9;14)(p11;p11), +14p+, +t(20;?)(q13;?), +t(20;?)(q13;?), +2 mar. A polyploidized clone with 120-150 chromosomes was also observed. DNA flow cytometry revealed only one abnormal peak, corresponding to a DNA index of 1.76. The other tumor, a uterine leiomyosarcoma, had the karyotype 61-67, X, -X, +1, +3, +5, +6, +7, +8, +9, +12, +13, +15, +t(1;1)(p32;q32), +der(1)t(1;8)(p13;q11), +del(2)(p11), +del(2)(q22), +del(2)(q22), +del(3)(p13), +i(5p),t(8;14)(q24;q24), +der(8)t(8;14) (q24;q24), +del(10)(p12),der(11)t(11;15)(p15;q11),t(16;?)(p13;?),t(16;?)(q24;?), der dic(17) (17pter----cen----17q25::hsr::17q25----cen----17pte r), +t(19;?)(p13;?), +der dic(20)(20pter----cen----20q12::hsr::20q12----cen----+ ++20pter), +mar. The DNA index was 1.59. The finding in these leiomyosarcomas of rearrangements of the same regions of chromosomes 12 and 14 that are involved in the tumor-specific t(12;14)(q14-15;q23-24) of uterine leiomyoma indicates that the same genes in 12q and 14q might be important in the pathogenesis of benign and malignant smooth muscle tumors.     

Cytogenetic abnormalities in hepatoblastoma: report of two new cases and review of the literature suggesting imbalance of chromosomal regions on chromosomes 1, 4, and 12

Two cases of hepatoblastoma with unique karyotypic changes are described. One case was that of a 2-year-old boy with an unbalanced chromosomal translocation involving 4q35 as the sole chromosomal abnormality. The clonal karyotype of this tumor was 46,XY,add(4)(q35)[3]/46,XY[9]. In the other case, that of a 2-year-old boy, karyotypic analyses revealed the clonal karyotype as 57,XY,+del(1)(p22),+2,+5,+6,+7,+8,+del(12)(p12),+18,+19,+20,+22[4]/46,XY[12]. Review of these two cases, together with previous reports, underscored the significance of numerical and/or structural chromosomal abnormalities of 1q, 4q, 2, 8, and 20 in the development of hepatoblastoma. The present results show that imbalance of the terminal region of 4q could be the sole chromosomal abnormality in a hepatoblastoma. We also found that imbalance of chromosomal regions on chromosomes 1 and 12 may contribute to the development of hepatoblastoma.     

一个染色体8p23.1缺失所致先天性心脏病家系的遗传学分析

目的明确1个先天性心脏病家系的遗传学病因,并探讨其可能的致病机制。方法联合应用G显带染色体核型、染色体微阵列分析(chromosomal microarray analysis,CMA)及多重连接探针扩增技术(multiplex ligation-dependent probe amplification,MLPA)3种技术对本研究中患左室心肌致密化不全(left ventricular noncompaction,LVNC)的患者及其胎儿行遗传学检测。结果患者的核型结果为mos45,XY,rob(15;21)(q10;q10)[36]/46,XY[64],其胎儿的核型未见异常;患者及其胎儿的CMA检测结果均为arr[hg19]8p23.1(11232919-11935465)×1。MLPA检出患者及其胎儿GATA4基因的7个外显子全部缺失。结论染色体8p23.1缺失是导致患者发生LVNC以及其胎儿发生室间隔缺损的原因,GATA4基因为关键致病基因。     

Atypical (7;19) translocation in acute myelomonocytic leukemia.

Chromosome studies were carried out after a 24-hour harvest of unstimulated bone marrow aspirate cell cultures from a 75-year-old male with a clinical diagnosis of acute myelomonocytic leukemia (FAB M4). Analysis of nine cells after trypsin-Giemsa banding (GTG) revealed two cell lines with a mosaic chromosome pattern, 46,XY/46,XY,t(7;19)(q22;p13.3). A review of the recent literature reveals one case of childhood ALL with a 46,XY/46,XY,t(7;19)(q11;q13) chromosome pattern [1] and a 46,XY,t(3q;11q),t(7q;19p),t(15;17)(q26;q22) in one patient with ANLL (FAB M3) [2]. The t(7;19)(q22;p13.3) seen in our case has not been reported as the sole specific clonal chromosome rearrangement in myeloid neoplasia. Interestingly, the plasminogen activator inhibitor type I, multi-drug resistance, and erythropoietin genes are located at band 7q22 and the insulin receptor gene is located at band 19p13.3. Both sites contain fragile site loci. The possible role of these fragile sites, genes, or other genes in the rearrangement can only be surmised.     

Acquired inv(9): what is its significance?

Pericentric inversion of the heterochromatic region of chromosome 9 [inv(9)] is a common heteromorphism in the general population. It is presumed familial as there are no reports of de novo inv(9) chromosomes in constitutional karyotypes. We report 2 cases of acquired inv(9) chromosomes; 1 patient with acute myeloid leukemia, 46,XY,inv(9)(p11q13)[11]/46,XY[9], and a second with severe anemia, 46,XX,inv(9)(p11q13)[14]/46,XX[6]. The acquired nature of the inv(9) was confirmed by constitutional karyotyping and/or molecular analysis. The inv(9) in these patients may be a de novo inversion that cytogenetically mimics the constitutional inv(9) heteromorphism. Alternatively, it may be the result of neocentromere activation in 9q due to epigenetic events associated with the disease in these patients that results in a metacentric chromosome similarly mimicking the constitutional inv(9). One previous report of an acquired inv(9) was in a patient with essential thrombocythemia. The differences in clinical presentation may represent different underlying mechanisms generating the inv(9). The significance of an acquired inv(9) is unknown and will require reporting of additional cases.     

Complex chromosome 9, 20, and 22 rearrangements in acute lymphoblastic leukemia with duplication of BCR and ABL sequences

Cytogenetic analysis was performed on bone marrow cells from a 28-year-old woman who was diagnosed with acute lymphoblastic leukemia (ALL). Her karyotype was: 46,XX,t(9;22)(q34;q11)[6]/47, XX,+8,t(9;22)(q34;q11)[4]/47,XX,+8,t(9;22)(q34;q11),del(20)(q11)[2]/46, XX,t(9;22)(q34;q11),del[20](q11)[7]/45,XX,der(9)t(9;22)(q34;q11),-20,-22 , +mar1[8]/45,XX,der(9)t(9;22)(q34;q11),-20,-22,+mar2[3]. Both marker chromosomes are dicentric and have the same size and banding pattern but different primary constrictions. Fluorescence in situ hybridization (FISH) demonstrated that both markers were derived from chromosomes 9, 20, and 22. FISH with the bcr/abl probe showed fusion of the BCR gene with the ABL gene; however, this fusion signal was present in duplicate on both marker chromosomes. To our knowledge, duplication of the BCR/ABL fusion signal on a single chromosome arm has not been reported before, except for the extensive amplification of BCR/ABL fusion signals in the leukemic cell line K-562. These data demonstrate that the marker chromosomes are the result of complex genomic rearrangements. At the molecular level, the BCR/ABL fusion gene encodes the p190 fusion protein. Similar findings have never been observed in any case of ALL.     

Distal 2q duplication: Report of two familial cases and an attempt to define a syndrome

Two cases of partial trisomy 2q are described, both resulting from a balanced translocation in one of the parents. In one case the chromosomes 2 and 11 were involved [paternal karyotype: 46,XY,t(2;11)(q33;q23)]; in the second case, chromosomes 2 and 8 [paternal karyotype: 46,XY,t(2;8)(q32;p23)]. When the two patients were compared to the few cases reported in the literature, it was concluded that the associated clinical syndrome is characterized by severe psychomotor retardation and relatively mild abnormalities involving skull and facies.     

Two new chromosomal abnormalities in chronic myelogenous leukemia 46,XY,t(9;15;22)(q34;q22;q11) and 46,XY,t(6;9;12;22)(p21;q34;q24;q11)

Two new variant cases of chronic myelogenous leukemia (CML) are presented. The first case is a 19-year-old male with a 46,XY,t(9;15;22)(q34;q22;q11) karyotype. The second case is a 75-year-old man with a 46,XY,t(6;9;12;22)(p21;q34;q24;q11) karyotype. In both cases, the prognosis was no different from those cases of CML with the standard t(9;22) as the only abnormality. We recommend that all unusual translocations be reported.     

Clonal cytogenetic abnormalities are predictor in developing non-Hodgkin lymphomas?

Pathological analysis is the cornerstone for diagnosing malignant lymphoma. Status of cytogenetic abnormalities is frequently left unexamined if no evidence of malignancy is found in pathological analysis. In this study, we presented 3 cases in which clonal cytogenetic abnormalities were detected but morphological alterations of the same tissue did not support malignant non Hodgkin lymphoma at the first lymph node biopsy. Case 1 is a 55-year-old female with lymphadenopathy neoplastic process confirmed by flow cytometry and polymerase chain reaction (PCR). Chromosome analysis revealed 47,XX,t(3;22)(q27;q11),+del(9)(p12)[16]/46,XX[4]. The pathological analysis of subsequent lymph node biopsy indicated diffuse large B-cell lymphoma (DLBCL). Case 2, a 74-year-old female, for whom the pathological analysis, molecular studies and flow cytometric analysis of the first lymph node biopsy found no evidence of clonal cell. Cytogenetic analysis demonstrated a terminal deletion of chromosome 7 and 1, and the patient received a second lymph node biopsy and splenectomy. A pathological diagnosis of splenic marginal zone lymphoma (SMZL) was made. In Case 3 who was a 66-year-old female with right cervical and axillary lymph node enlargement. Cytogenetic analysis showed clonal karyotypic abnormalities: 48,XX, t(14;18)(q32;q21) [13]/46, XY [7]. The diagnosis of follicular lymphoma was rendered by the second biopsy of axillary lymph node according to the analysis of morphology and immunohistochemistry. We propose that clonal cytogenetic abnormalities may be a high potential risk for developing non-Hodgkin lymphomas. Follow-up and rebiopsy must be performed in patients who are cytogenetically abnormal but morphologically benign.