Primary perivascular epithelioid cell tumor of the bladder

The perivascular epithelioid cell family of tumors includes angiomyolipoma, clear cell “sugar” tumor of the lung, lymphangioleiomyomatosis, and clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres. Less frequently, perivascular epithelioid cell tumors arise in various other locations throughout the body including soft tissue, bone, and visceral organs. We report a case of a 23-year-old man who presented with 2-month history of frequent micturition and odynuria. Based on clinical examination, ultrasound computed tomography imaging, surgical operation, and histopathologic studies, a definitive diagnosis was made. Further characteristic images and pathology of this disease are discussed.     

Incidental perivascular epithelioid cell tumor in an inguinal hernia sac

Perivascular epithelioid tumors (PEComa) are uncommon mesenchymal neoplasms demonstrating positivity for muscular and melanocytic immuno-markers. Included in this category are angiomyolipoma, lymphangioleiomyomatosis, and clear cell sugar tumors. Lesions which do not fit into these categories are classified as “not otherwise specified”. We present a case of an incidentally discovered PEComa within inguinal hernia sac contents in a 70-year-old woman. It consisted of spindled and epithelioid cells with bland oval nuclei, small nucleoli and clear to light eosinophilic cytoplasm. There was no atypia or mitoses. The lesion was strongly positive for HMB45 and smooth muscle actin. Pelvic soft tissue and peritoneal PEComas are rarely reported in literature and very little is known about their prognosis. We discuss the immunohistochemistry, differential diagnosis, and pathogenesis of PEComas.     

Malignant perivascular epithelioid cell tumor of the kidney with rare pulmonary and ileum metastases

Aims: To report one case of malignant perivascular epithelioid cell tumor (PEComa) of the kidney with rare pulmonary and ileum metastases and analyze its clinicopathological features. Methods: We analyzed the clinicopathological features of one case of malignant PEComa of the kidney with pulmonary and ileum metastases. Immunohistochemistry staining was performed. Results: The patient was a 48-year-old man with a renal mass approximately 14 cm × 11 cm × 8 cm in size. Microscopically, the tumor was mainly composed of polygonal epithelioid cells with dense eosinophilic cytoplasm and round nuclei with small nucleoli. Focal tumor cells showed pleomorphism with multinucleated giant cells and prominent nucleoli. The tumor cells nests were surrounded by thick-walled irregular blood vessels. Focal fat cells were found within the tumor. Hemorrhage and coagulative necrosis were also present. The tumor cells were positive for vimentin, HMB45, and Melan-A, and focally positive for SMA and S-100 protein. After 5 years and 5.6 years of nephrectomy, the tumor metastasized to the right lung and ileum, respectively. Conclusion: We first reported one case of malignant PEComa of the kidney with pulmonary and ileum metastases. Metastatic PEComa of the lung and ileum should differentiate from primary carcinoma, metastatic carcinoma, malignant melanoma, and gastrointestinal stromal tumor.     

Primary perivascular epithelioid cell tumor in the rectum: A case report and review of the literature

Perivascular epithelioid cell tumor (PEComa) is a rare collection of tumors arising in a wide array of anatomic locations. It is characterized by the presence of a peculiar population of myomelanocytic marker-positive perivascular epithelioid cells, and is commonly detected in the uterus. The colorectal area is an uncommon site for primary PEComa. In this study, we describe a 17-year-old patient presenting with a rectal polyp. Histologically, the tumor consisted of sheets of round to polygonal epithelioid cells with clear and granular cytoplasm, and a prominent capillary network. Some of the tumor cells were positive for Fontana-Masson staining. Immunohistochemically, the tumor cells were positive for HMB-45, and were negative for cytokeratin, vimentin, S-100 protein, actin, desmin, EMA, CD34, and c-kit. After finding melanosomes or premelanosomes at the ultrastructural level, the diagnosis of PEComa was made. Although PEComa arising within the intestinal tract is unusual and clinically unexpected, PEComa should be considered in the differential diagnosis of rectal polypoid lesions.     

Malignant perivascular epithelioid cell tumor of the retroperitoneum

Perivascular epithelioid cell tumors (PEComas) are a rare type of mesenchymal neoplasms characterized by a proliferation of perivascular cells with an epithelioid phenotype and expression of myo-melanocytic markers. The majority of PEComas seem to be benign and usually their prognosis is good. Malignant cases are extremely rare, exhibiting a malignant course with local recurrences and distant metastases. We herein report a case of a malignant PEComa arising in the retroperitoneum. The patient was a 55-year-old woman experiencing abdominal discomfort for approximately one month. Ultrasound and computer tomography (CT) scans of the abdomen revealed a solid mass arising from the retroperitoneum. Microscopically, the tumor was composed of epithelioid cells mixed with spindled cells. The nucleus had significant atypia, and the mitoses were obvious. The focal intravascular tumor embolus was visible. Immunohistochemically, the epithelioid tumor cells were positive for HMB45 and Melan-A, and the spindled tumor celLs were positive for SMA and desmin. Seven months after a surgical resection, an ultrasound revealed liver metastases. In conclusion, the malignant PEComas of the retroperitoneum is a very rare neoplasm with unique morphological and immunohistochemical characteristics. It should be differentiated from other epithelioid cell tumors of the retroperitoneum.     

原发性胃癌的比较基因组杂交研究

目的　研究胃癌发生和发展过程中是否涉及其它未知的癌基因和抑癌基因。方法　采用比较基因组杂交法(com parative genom ic hybridization,CGH)分析了43 例原发性胃癌。结果　3p(8/43)、8q(8/43)、20 号染色体[20(9/43),20p(7/43)、20q(4/43)]、12q(16/43)、13q(12/43)的扩增,19 号染色体[19(15/43),19p(13/43)]、17 号染色体[17(8/43),17p(10/43)]、16 号染色体(10/43)和1p(11/43)区域的缺失为胃癌的特征性变化。结论　提示3p、8q、12q、13q、20 号染色体、17 号染色体、16 号染色体和1p 区域可能存在一些与胃癌形成相关的未知基因。     

Perivascular epithelioid cell tumor in the duodenum: challenge in differential diagnosis

Defined as a family of scarce mesenchymal neoplasm which distinctively co-express melanocytic markers and muscle markers, perivascular epithelioid cell tumors (PEComas) have been reported almost everybody site. Perivascular epithelioid cell tumors-not otherwise specified (PEComas-NOS) arising in the gastrointestinal (GI) tract are still restricted into sporadic case reports. Herein we present a case of GI PEComas-NOS which occurs in the duodenum of a 27-year-old male. Our initial diagnosis tended to gastrointestinal stromal tumor or smooth muscle tumor till the correct diagnosis of perivascular epithelioid cell tumor (PEComa) was established by postoperative pathological examination. We also make a literature review of GI PEComas-NOS and highlight the challenge it brings to the differential diagnosis.     

利用比较基因组杂交技术分析横纹肌肉瘤中染色体基因组的变化特征

目的 探讨横纹肌肉瘤(RMS)基因组DNA的变化特征.方法 在一步法RT-PCR检测所有标本PAX3/PAX7-FKHR mRNA融合基因表达情况的基础上,应用比较基因组杂交技术分析25例原发性RMS患者,其中腺泡状横纹肌肉瘤(ARMS)10例,胚胎性横纹肌肉瘤(ERMS)12例,多形性横纹肌肉瘤(PRMS)3例.根据融合基因表达情况、组织学分型、临床分期、组织学分级、性别和年龄进行分组比较.同时收集RMS细胞株A204(腺泡型)、RD(胚胎型)作为对照.结果 25例RMSCGH分析结果显示:(1)RMS中发生DNA拷贝数扩增最常见的部位是2p和12q,其他依次为6p、9q、10q、1p、2q、6q、8q、15q和18q(30%),发生DNA拷贝数丢失最常见的部位是3p、11P和6p(30%).(2)ARMS扩增最常见的染色体臂是12q、2p、6、2q、4q、10q和15q(30%),缺失最常见的染色体臂是3p、6p、1q、5q(30%);ERMS扩增最常见的染色体臂是7p、9q、2p、18q和1 p、8q(30%),缺失最常见的染色体臂是11p.基因组变化在不同的组织学分类中差异无统计学意义(P0.05).(3)伴有融合基因组扩增最常见的染色体臂是12q、2、6、10q、4q和15q(30%),缺失最常见的染色体臂是3 p、6p、5q(30%);不伴有融合基因组扩增最常见的染色体臂是2p、9q、18q(30%),基因组缺失最常见的染色体臂是11p和14q(30%).12q扩增在这两组间的差异有统计学意义(P<0.05),并多见于伴有融合基因的RMS.(4)在临床分期分组中,9q扩增在Ⅱ期和Ⅲ～Ⅳ期间差异有统计学意义(P<0.05),且多见于Ⅱ期患者.结论 (1)2p、12q、6p、9q、10q、lp、2q、6q、8q、15q、18q扩增及3p、11p、6p缺失可能与RMS发病相关;(2)12q扩增可能与融合基因相关;(3)9q扩增可能与RMS发病早期有关.     

High-grade mucinous tubular and spindle cell carcinoma: comparative genomic hybridization study

Mucinous tubular and spindle cell carcinoma (MTSCC) has recently been integrated into the World Health Organization classification. Although MTSCC is generally a low-grade carcinoma, MTSCC with high-grade morphology has been recently reported. We present the first case of high-grade MTSCC with comparative genomic hybridization findings. A 60-year-old Japanese man presented with weight loss and general fatigue. He underwent radical nephrectomy because of the clinical diagnosis of renal cancer. Histologic examination of renal tumor showed findings of high-grade MTSCC. Comparative genomic hybridization analysis showed gain of chromosomes 1q, 7, 16, 19q, and Y and loss of chromosomes 1p, 6p, 8p, 11q (del(11)(q23)), and 13. G-band karyotype showed gain of chromosomes 2, 3, 5, 7, 12, 16, and 20 and loss of chromosome 15. Results of our molecular genetic analysis support the idea that high-grade MTSCC is a real counterpart of low-grade MTSCC. There is no evidence to designate such tumors as unclassified renal cell carcinoma.     

Comparative genomic hybridization pattern of non-anaplastic and anaplastic oligodendrogliomas--a meta-analysis

Many oligodendrogliomas (ODG) have been investigated by comparative genomic hybridization (CGH). To visualize characteristic aberration profiles of non-anaplastic in a comparison with anaplastic ODGs, we performed a meta-analysis of the CGH results of all 89 cases published so far. Therefore, we expanded all given aberrations to the maximum of 850 GTG band resolution. The frequencies of each chromosomal band affected by a genetic imbalance were calculated for WHO grades II and III separately. In non-anaplastic ODGs, -1p and -19q were the most prominent aberrations. In anaplastic ODGs, +7, -4q, -9p, -10, and -15q emerged additionally. We could confirm the existence of three disjunct genetically defined subgroups of ODGs, characterized by -1p/-19q (n=58, 65%, subgroup A), +7/-10 (n=6, 7%, subgroup B) or the absence of either of the two patterns (n=25, 28%, subgroup C). Interestingly, we found a unique aberration pattern in subgroup C (-1p31, -4q, -11p15, -18q, -22q, +17p, +17q) that was different from subgroups A and B, which could indicate a unique molecular carcinogenetic pathway of this ODG subset. Scrutinizing published putative progression markers of ODG, we found that only +7, -10, and -15q significantly correlated with a higher grade of malignancy. Summing up, the expansion of the CGH results to the 850 GTG band resolution enabled a meta-analysis to visualize WHO grade-specific aberration profiles in ODG for the first time.     

Large cell neuroendocrine carcinoma of the uterine cervix with cytogenetic analysis by comparative genomic hybridization: a case study

Large cell neuroendocrine carcinoma (LCNEC) of the uterine cervix is a newly introduced category of the revised World Health Organization classification. We reported a case of cervical LCNEC with cytogenetic analysis by comparative genomic hybridization (CGH). The cervical tumor showed moderately increased mitotic activity (8-14 mitotic figures per 10 high-power fields) and focal necrosis, which made it problematic to differentiate from atypical carcinoid. CGH analysis failed to detect chromosome 11q loss that has been reported to be characteristic of pulmonary atypical carcinoids. Furthermore, chromosome 3q amplification, which has been detected frequently in pulmonary small cell carcinomas and LCNECs but not in pulmonary typical and atypical carcinoids, was the most remarkable chromosomal aberration. Although CGH reports are extremely rare in neuroendocrine tumors of the uterine cervix, specific chromosomal aberrations may be useful in their distinction.     

Perivascular epithelioid cell tumor (PEComa) of soft tissue: case report with ultrastructural study

A perivascular epithelioid cell tumor (PEComa) arising in the abdominal wall of a 44-year-old female is described. The lesion was a well-circumscribed but unencapsulated, rubbery, subcutaneous mass measuring 3.5 x 3.5 x 3.0 cm which was removed by simple excision. It was characterized by a nest- or sheet-like arrangement of round to polygonal cells with round nuclei and abundant clear to slightly eosinophilic cytoplasm containing glycogen. There was mild to moderate nuclear pleomorphism with mitotic activity of 6 per 10 high power fields. A short fascicular proliferation of the tumor cells was observed focally. The stroma contained abundant small vascular channels with hyalinization. Immunohistochemically, the tumor cells were strongly positive for vimentin, epithelial membrane antigen, alpha-smooth muscle actin, and HMB45. Ultrastructural examination showed poorly differentiated mesenchymal tumor cells without premelanosomes. There was local recurrence 6 years after excision. Pathologists and clinicians should be aware of the existence of PEComa in soft tissue and should differentiate it from other similar lesions.     

Clonal relationship of tumor nodules in hepatocellular carcinoma: a hierarchical clustering analysis of comparative genomic hybridization data

Information on the clonal relationship between tumor nodules in patients diagnosed with hepatocellular carcinoma (HCC) holds prognostic significance in the prediction of recurrence and postoperative treatment. Here, we investigated the clonal relationships in 11 focal nodules from 5 patients with HCC by comparative genomic hybridization (CGH) and spectral karyotyping. CGH analysis indicated tumor nodules in 5 (100%) of 5 cases to share similar patterns of genomic imbalances, suggesting nodules to be clonally related. This clonal relationship was further substantiated in 2 cases, where spectral karyotyping analysis indicated identical structural rearrangements between focal tumors. Few studies have attempted to differentiate multicentric growth from intrahepatic dissemination in HCC using CGH analysis; however, data interpretation remained subjective. In this study, we have extended our data to include published CGH findings on 57 nodules derived from 19 HCC cases. Simulation of CGH findings by unsupervised 2-way hierarchical clustering indicated tumor nodules in 20 (83.3%) of 24 cases to cluster concordantly, signifying a high incidence of clonal similarity. In sum, bioinformatic analysis of genomic profiles may represent a reliable research tool in analyzing clonal relationships among tumor nodules.     

Malignant perivascular epithelioid cell tumor of the colon: report of a case with molecular analysis

Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal neoplasm, and malignant cases are extremely rare. A case of malignant PEComa arising in the colon is described herein. The patient was a 43-year-old Japanese woman without a history of tuberous sclerosis complex. The tumor occurred in the abdominal cavity attached to the serosal side of the descending colon. Histologically, the tumor consisted of sheets or closely packed nests of epithelioid cells with clear or eosinophilic cytoplasms. The tumor cells were positive for HMB-45 but negative for S-100 protein and cytokeratins by immunohistochemical staining. Ki-67 labeling index was 2.9%. Peritoneal dissemination of tumor occurred at 20 months and the patient died of tumor at 38 months after the initial operation. This was considered to be a case of malignant PEComa, based on the histological and clinical features. Tumor cells showed overexpression of cyclin D1 but lacked the loss of heterozygosity of the TSC1 and TSC2 genes. The result suggests that the overexpression of cyclin D1 may play an important role in the tumorigenesis of PEComa. Because PEComas can behave in an aggressive manner, careful follow up is warranted.     

Comparative genomic hybridization as a tool in tumour cytogenetics

The quality of cytogenetic analysis of solid tumours has greatly improved in the past decade, but a number of technical difficulties remain which limit the characterization of solid tumour chromosomes by conventional cytogenetics alone. The identification of regions of chromosomal abnormality has been aided by the introduction of molecular cytogenetic techniques such as fluorescence in situ hybridization (FISH). Of these, a recently developed approach, comparative genomic hybridization (CGH), has had a particular impact on the cytogenetic analysis of solid tumours. It incorporates the sensitivity of in situ techniques and overcomes many of the drawbacks of conventional cytogenetic analysis. This review first outlines the CGH method, giving details for the preparation of DNA probes and target human metaphase chromosomes together with information on the in situ technique and data handling criteria used in our laboratory. It then presents an overview of some of the current applications of CGH, together with a discussion of future directions in the field. Copyright © 1999 John Wiley & Sons, Ltd.     

Sclerosing variant of perivascular epithelioid cell tumor in the female genital organs

Perivascular epithelioid cell tumor (PEComas), other than angiomyolipoma, clear cell 'sugar' tumor of the lung, and lymphangioleiomyomatosis, is an uncommon mesenchymal neoplasm that arises in the soft tissue and visceral organs. We report herein two cases of sclerosing PEComa; a distinctive variant of PEComa, which is characterized by extensive stromal hyalinization, occurring in the uterus and broad ligament. The patients were 34- and 51-year-old females with no family history of tuberous sclerosis complex. Macroscopically, the tumors had white to gray cut surfaces and were microscopically composed of predominantly spindle- to polygon-shaped cells with clear to slightly eosinophilic cytoplasm and pleomorphic nuclei focally arranged in a perivascular pattern, accompanied by marked stromal hyalinization. These tumor cells were immunohistochemically positive for HMB45 and α-smooth muscle actin. Although this variant of PEComa is very rare, this entity should be considered as a potential primary neoplasm of the female genital organs.     

Chromosome aberrations associated with centrosome defects: a study of comparative genomic hybridization in breast cancer

Centrosome abnormalities occur frequently in various tumors and can cause chromosomal instability and eventually promote cancer development. We investigated the chromosome aberrations associated with centrosome abnormalities in 30 cases of breast cancer, combining immunohistochemical staining and comparative genomic hybridization. Except for some common chromosome alterations (including gains of 1q, 8q, 17q, 20q, and Xq and losses of 8p, 11q, 13q, 14q, 16q, 17p, 22q, and Xp) that have also been seen more frequently in other studies, we discovered some new changes that have rarely been reported, including gains at 2p, 5p, 10p, 15q, 16p, 18q, 21q, and 22q and losses at 6p, 8p23, 11p13-pter, 13q34, and 14q32-qter. We also identified some changes (such as gains of 17q, 20q, and Xq and losses of 17p, 13q, and 14q) harboring candidate genes. We also explored the expression of centrosome protein in different molecular subtypes of breast cancer. Our findings provide a new way to explore the molecular mechanisms of breast tumorigenesis and accordingly potential new targets for therapy for this disease.