低分化滑膜肉瘤临床病理及分子遗传学研究

目的：研究低分化滑膜肉瘤的临床病理学特点及其分子遗传学表现。方法：收集低分化滑膜肉瘤标本121例，采用形态学观察和免疫组化染色，并用RT－PCR方法在石膜包埋组织中检测SYT－SSX融合mRNA表达。结果：12例低分化滑膜肉瘤中细胞型4例，大细胞型6例，高度恶性梭形细胞型2例。8例有随访资料其中4例死于肿瘤，平均生存时间18个月。免疫组化表现为CK和（或）EMA阳性，以EMA阳性率较高，同时vimentin阳性。S－100蛋白也有较高阳性率，多呈局灶或散在阳性。RT－PCR方法均可检测到SYT－SSXmRNA表达，对照组12例肿瘤包括恶性周围神经 鞘膜瘤、尤因肉瘤和恶性血管外皮瘤SYT－SSX检测全部阴性。结论：低分化滑膜肉瘤有其形态学及免疫表型特点，分子遗传学检测SYS－SSX融合mRNA有助于诊断和鉴别诊断。     

Establishment and characterization of a new human synovial sarcoma cell line, HS-SY-II.

BACKGROUND: The line of differentiation in synovial sarcoma still remains controversial. Thus far, only a few human synovial sarcoma cell lines have been described. However, their morphologic characteristics have not been fully established. EXPERIMENTAL DESIGN: We established a new synovial sarcoma cell line (HS-SY-II) from pleural effusion with lung metastasis in a typical example of the monophasic spindle cell type. The HS-SY-II cells, in vitro and in vivo, were examined by light microscopy, immunohistochemistry, electron microscopy, and cytogenetics. RESULTS: The HS-SY-II cells showed a hypertriploid karyotype with complex chromosome abnormalities including pathognomonic t(X;18)(p11;q11), and have been stably maintained for more than 40 months in vitro, showing rather small spindle or polygonal shape without conspicuous pleomorphism. Histologic features of initially and serially transplanted tumors in nude mice were essentially the same as those of the original sarcoma, corresponding to the monophasic spindle cell variant with a prominent palisading pattern and calcified foci in parts. The HS-SY-II cells in vitro and in vivo similarly expressed vimentin and cytokeratin by immunohistochemistry, and also exhibit the same ultrastructural features such as irregularly shaped nuclei with prominent nucleoli, many paranuclearly running intermediate filaments, and filopodia-like processes. CONCLUSIONS: This HS-SY-II cell line retaining the distinct morphological characteristics as the monophasic spindle cell type of synovial sarcoma therefore will be extremely useful for various pathomorphologic investigations on synovial sarcoma.     

Identification of poorly differentiated synovial sarcoma: a comparison of clinicopathological and cytogenetic features with those of typical synovial sarcoma

AIMS: Poorly differentiated areas in synovial sarcomas (SS) are known to be associated with a poorer prognosis. The aim of our study was to describe the morphological spectrum of poorly differentiated synovial sarcomas (PDSS) and refine the criteria for their recognition. METHODS AND RESULTS: The clinicopathological features of 28 PDSS were compared with those of 26 classic SS. Common cell types in PDSS included epithelioid, spindle and Ewing sarcoma-like small round cells. Unusual features included presence of desmoplastic small cell tumour-like areas and extraskeletal myxoid chondrosarcoma-like areas. The presence of necrosis (P = 0.002), a mitotic rate over 10/10 high-power fields (P < 0.001), a haemangiopericytomatous vascular pattern (P < 0.001) and vascular invasion (P = 0.003) were significantly associated with PDSS, while mast cells (P < 0.001), calcification (P < 0.001) and hyaline bands (P < 0.001) were significantly associated with classic SS. Poorly differentiated areas showed increased proliferative activity with Ki67. PDSS showed a tendency to be larger (P = 0.008) and to be located in proximal more than distal sites (P = 0.025). Three entirely poorly differentiated tumours were diagnosed by demonstration of the t(X;18)(p11;q11) translocation. PDSS showed additional cytogenetic abnormalities. CONCLUSIONS: Poorly differentiated synovial sarcomas show a spectrum of histological features, which may simulate other malignant neoplasms. The diagnosis of entirely poorly differentiated synovial sarcomas requires cytogenetic analysis.     

荧光原位杂交及TLE1免疫组织化学在小细胞低分化型滑膜肉瘤诊断中的应用

滑膜肉瘤(synovial sarcoma)占软组织肉瘤的5%～10%,以青壮年多见,主要发生于四肢大关节附近,多数生长缓慢.根据组织学形态及分化程度,滑膜肉瘤分可为5种类型;单相纤维型、单相上皮型、双相型、低分化梭形细胞型和小细胞低分化型(small cell variant of poorly differentiated synovial sarcoma),其中后者较为罕见,是病理学诊断中的难点.     

A unique 8;16 translocation in two infants with poorly differentiated monoblastic leukemia

Acute monoblastic leukemia is nonrandomly associated with abnormalities involving 11q. Two infants, one a neonate and the other 19 months of age, had the same hitherto undescribed karyotypic abnormality, t(8;16)(p11;p13), associated with acute nonlymphocytic leukemia M5a. The older child had an additional translocation, t(10;11)(q11;p15), but the chromosome arms affected were the opposite to those described in acute nonlymphocytic leukemia M5a of childhood. Therefore, it is postulated that genes involved in monocytic differentiation may be situated on 8p11 or 16p13, as well as on 11q.     

Acral myxoinflammatory fibroblastic sarcoma with unique clonal chromosomal changes

Acral myxoinflammatory fibroblastic sarcoma is a rare tumor of the distal extremities. We present the hitherto unreported karyotypic abnormalities of this new entity. The tumor presented as a mass in the dorsum of the foot in a 53-year-old woman and showed the typical virocyte-like and lipoblast-like cells in a myxoid and inflammatory background. Cytogenetic analysis revealed a complex karyotype with a reciprocal translocation t(1;10) (p22;q24) in addition to the loss of chromosomes 3 and 13. Fluorescence in situ hybridization with the 769E11YAC and BAC 31L5 and 2H23 probes showed the breakpoint to be located proximally to BCL10 and distally to GOT1 genes on chromosomes 1p22 and 10q24, respectively. The presence of these clonal chromosomal changes supports the neoplastic nature of acral myxoinflammatory fibroblastic sarcoma and underscores that it represents a separate entity.     

Establishment and characterization of a poorly differentiated lethal human endometrial carcinoma cell line (NOU-1) with karyotype 46,XX

Immortal gynecologic cell lines, especially those of endometrial origin are diverse with multiple chromosomal alterations, making the study of origin and molecular genetic characteristics of such neoplasms difficult, if not impossible. We have established a new epithelial, poorly differentiated endometrial adenocarcinoma cell line (NOU-1) with a 46,XX chromosome complement. To confirm the tumor characteristics, we injected this cell line subcutaneously into the nude mouse. The tumor grown in vivo had the identical histology and the same 46,XX chromosome complement as the original tumor excised from the patient. The cells from the original tumor and those in the nude mouse shared the same characteristics with respect to histopathology, immunohistochemistry, steroid hormone receptor content, and growth characteristics. We report on the only established cell line of a highly aggressive, poorly differentiated endometrial adenocarcinoma with 46,XX chromosome complement where both estrogen and progesterone receptors are absent.     

Patterns of keratin polypeptides in 110 biphasic, monophasic, and poorly differentiated synovial sarcomas

Synovial sarcoma is a mesenchymal neoplasm of unknown histogenesis that shows various degrees of epithelial differentiation. It is known to contain simple epithelial keratins, and the possibility of complex epithelial keratin expression has been suggested. In this study, we immunohistochemically examined 110 well-documented synovial sarcomas including 44 biphasic, 48 monophasic, and 18 poorly differentiated (undifferentiated, highly mitotically active) tumors for 11 different keratin (K) polypeptides of the Moll catalogue. The epithelia of biphasic synovial sarcomas showed consistent, extensive reactivity for K7, K8, K14, K18, and K19. Other keratins seen in the epithelia of biphasic tumors included K17 (variable, in 77%), K13 (25%), K16 (23%), and K6 (24%) in the minority of biphasic tumors, predominantly in stratified-appearing epithelia. K10 was detected only focally in one case that showed keratinizing squamous differentiation. Focal expression of K20 was seen in 27% of cases. Monophasic synovial sarcomas had a more limited keratin repertory. Simple epithelial keratin positivity was detected, usually focally for K7 (79%), K19 (60%), K8 (45%), and K18 (46%). Two cases showed more extensive keratin positivity in the spindle cells. The monophasic tumors showed limited positivity for complex epithelial keratins: K14 (28%) and K17 (10%). K20 was detected focally in 6% of the monophasic tumors; other keratins were not detected. The poorly differentiated synovial sarcomas showed limited simple epithelial keratin reactivity, usually limited to scattered cells: K19 (61%), K7 (50%), K18 (47%), K8 (33%), but five cases showed more extensive positivity. Complex epithelial keratins were scant: K14 in one case and K17 in two cases. The immunoreactivity of capillary endothelia seen for K7 and K18 (but not for K8 and K19 with the antibodies used) is a potential diagnostic pitfall, and may cause overdiagnosis of synovial sarcoma if not properly recognized. In summary, we show complex patterns of keratins in synovial sarcoma, especially in the biphasic tumors. Such patterns establish a baseline in differential diagnostic considerations, and give an insight into the complex epithelial differentiation of this enigmatic mesenchymal tumor. Received: 17 February 2000 / Accepted: 3 April 2000     

Poorly differentiated synovial sarcoma. A light and electron microscopic study.

Few studies of the ultrastructural features of synovial sarcoma have appeared in the literature. The case under study represented a poorly differentiated synovial sarcoma with a predominant fibrosarcomatous component and a few areas with epithelioid and pseudoacinar patterns. Ultrastructurally, the cellular elements of the varied histologic patterns were similar. Basement membranes and desmosomes were absent, and the cell surfaces facing the acinar lumen exhibited multiple microvilli. It appears from a comparison of our studies with the previous reports that the fine structure of this tumor varies according to the degree of histologic differentiation.     

A new skeletal dysplasia syndrome with dwarfism, craniofacial anomalies, and unique radiographic findings

We report on a boy from a consanguinous marriage who has a unique skeletal dysplasia, marked dwarfism, mild developmental delay, eye abnormalities, and cranofacial and skeletal changes that have not been described previously.     

Chondrosarcoma‐like metastasis from a poorly differentiated uterine cervical squamous cell carcinoma. A unique morphology and diagnostic pitfall in cytology

Rare cases of metastatic squamous cell carcinoma with chondroid differentiation from esophageal primary have been reported but none from the uterine cervix. Given the rarity of this phenomenon and potential diagnostic pitfall, we present this unusual case. The patient is a 25‐year‐old woman who presented with shortness of breath. Computerized tomography (CT) showed several lung and pleural‐based nodules. CT‐guided core biopsy with touch preparations were performed on the pleural‐based nodule. The touch preparations showed large, spindle‐to‐oval shaped cells with pleomorphic nuclei embedded in metachromatic chondroid stroma. The core biopsies also showed predominantly round‐to‐spindle shaped cells with hyperchromatic nuclei and prominent nucleoli embedded in a cartilaginous matrix. Her past medical history is significant for a poorly differentiated squamous cell carcinoma of the cervix, which on review showed a typical non‐keratinizing squamous cell carcinoma without sarcomatous differentiation. Immunohistochemical stains performed on the pleural‐based mass showed tumor positivity for AE1/AE3, CK5/6, p16, and S‐100. Similar results were seen when the cervical tumor was stained retrospectively. Human papilloma virus (HPV) in situ hybridization performed on both the pleural‐based mass and cervical tumor detected the presence of high‐risk HPV subtypes including 16 and 18. These findings supported a lung metastasis from the prior cervical carcinoma. This case emphasizes that cervical carcinoma can develop mesenchymal (chondrosarcomatous) differentiation in metastasis even in tumors presenting with pure epithelial phenotype. Awareness of this occurrence especially on limited cytology material, knowledge of the prior history and use of ancillary tests are extremely helpful in arriving at the correct diagnosis. Diagn. Cytopathol. 2017;45:750–753. © 2017 Wiley Periodicals, Inc.     

Littoral cell angiomatosis with poorly differentiated adenocarcinoma of the lung

We report on a 64-year-old male United States Navy Veteran of World War II, one of two identical twins, diagnosed with littoral cell angiomatosis of the spleen, liver, and lymph nodes, later found to have a massive poorly differentiated adenocarcinoma involving the mediastinum, adjoining lung, and sternum with widespread metastases. Herein we include our findings at autopsy, pertinent immunohistochemical studies, and a review of the literature pertaining to littoral cell angiomatosis with comment on its association with visceral malignancies.