磷酸盐尿性间叶肿瘤12例临床病理分析

目的：探讨磷酸盐尿性间叶肿瘤的临床病理学特征。方法回顾性分析12例磷酸盐尿性间叶肿瘤的临床资料、组织学及免疫表型,并复习相关文献。结果12例中男性8例,女性4例,年龄23~63岁,平均40．5岁;病程1~14年,平均5．6年;患者均有不同程度的骨痛、关节痛和活动受限伴低血磷、高尿磷;肿瘤最大径1~7．5 cm,平均2．7 cm;肿瘤主要由梭形细胞构成,部分病例伴有破骨样多核巨细胞,血管丰富,可见簇状厚壁畸形血管、薄壁血管、散在脂肪岛及软骨样细胞;7例伴有不规则钙盐沉积,2例伴条索状上皮,其中CK(AE1/AE3)阳性;10例核分裂象少见,2例核分裂象多见,其中1例肿瘤细胞异性明显;瘤细胞均表达vimentin、CD56(其中2例分别为弱阳性和灶阳性),11例NSE阳性,8例CD99阳性,7例BCL-2阳性,4例CD34和6例SMA呈不同程度阳性,10例Ki-67增殖指数≤5%,2例分别为10%、25%。随访时间2~108个月,其中2例分别于术后72、84个月复发,其余病例均未见复发。结论磷酸盐尿性间叶肿瘤多表现为良性或低度恶性,其组织学形态多变且缺乏特异性,掌握其共性特征并紧密结合临床才能正确诊断。     

磷酸盐尿性间叶组织肿瘤七例临床病理分析北大核心CSCD

磷酸盐尿性间叶组织肿瘤（phosphaturic mesenchymal tumor,PMT）是一种罕见的肿瘤,与肿瘤性骨软化症密切相关。组织学表现复杂多样且缺乏明确的特征性,常在临床或病理诊断中被误诊,我们收集7例PMT病例。并结合文献探讨其临床特点、影像学表现、病理特征及鉴别诊断。     

磷酸盐尿性间叶性肿瘤1例

<正>患者男性,48岁,反复右侧腰痛5年,加重1年。左侧腹股沟外侧可触及一大小4 cm×6 cm包块,质地稍硬,局部无压痛,边界清楚,活动度可。胸部CT:右侧第2、5、6、7、8骨皮质欠连续,部分可见骨痂生长。实验室检查:术前血磷0.49 mmol/L(正常值0.81～1.60 mmol/L),术后血磷0.94mmol/L。B超示:左侧腹股沟外侧皮下软组织层内见一大小55 mm×37 mm×24 mm的囊实性混合包块,以囊性为主。     

腕部磷酸盐尿性间叶性肿瘤1例

<正>患者女性,71岁,因左手疼痛10个月、加重2个月就诊于安徽医科大学附属阜阳医院。患者10个月前无明显诱因出现左手疼痛,活动后加重,休息后稍缓解,在当地医院行小针刀治疗,症状缓解不明显。CT检查示左侧第一掌骨下方外侧皮下软组织内见一不规则高密度影,大小2.4 cm×1.8 cm, CT值约204 HU(图1),左侧腕骨内见多发小囊状透亮影,部分腕骨间隙狭窄;查体：左侧第一掌骨基底部稍红肿,可触及一囊实性包块,     

骨软化或佝偻病相关的间叶组织肿瘤临床病理分析

目的 探讨骨软化或佝偻病相关的间叶组织肿瘤的临床病理特点。方法 回顾分析10例患者的临床资料,观察10例骨软化相关的肿瘤组织的形态和免疫表型[免疫组织化学SP法染色,所用抗体包括波形蛋白、S-100、平滑肌肌动蛋白（SMA）、结蛋白、CD34、AE1／AE3、Ki-67、HMB45]。结果 患者男性6例,女性4例,年龄范围28～69岁（平均45．6岁）;患者均有2～27年（平均9．6年）骨痛、关节痛和活动困难的病史,检查发现低血磷、高尿磷;肿瘤最大径1～7cm不等（平均3．5cm）;瘤组织为间叶组织来源（仅2例颌骨病变中见不明显的条索状上皮）,可见多少不等的梭形纤维母细胞样细胞、脂肪细胞、软骨样细胞、黏液样细胞等,瘤组织富于血管,8例病变中有少见的絮状或不规则砂砾样钙盐沉积,2例发生于软组织的肿瘤周边见骨壳形成。3例组织中可见非尿酸盐结晶：9例细胞分裂象少见,1例核分裂象多见并且异型性明显;瘤细胞波形蛋白阳性,5例SMA部分阳性,3例CD34部分瘤细胞阳性,结蛋白、S-100、AE1／AE3均阴性,Ki-67指数（8例≤4％,仅1例为30％）;AB／PAS染色：8例肿瘤黏液基质和血管周围黏液样变呈AB染色阳性。结论 骨软化相关的肿瘤多为良性或低度恶性的间叶组织肿瘤,因组织学具有多样性而易误诊,掌握其共性特征并结合临床资料方能正确诊断。     

胃肠道间叶组织源性肿瘤的超声诊断价值分析

目的探讨超声检查对胃肠道间叶组织源性肿瘤的诊断价值。方法25例经手术病理证实的胃肠道间叶组织源性肿瘤患者．其中男性9例,女性16例;年龄29～80岁．平均年龄57-2岁。回顾性分析其超声表现,并对超声诊断结果与病理诊断结果进行对比分析。结果间质瘤呈圆形或椭圆形,形态规整,边界清楚,内呈均匀低回声,血液运行不丰富;较大者形态不规整．内部回声不均并可见液性区,血液运行丰富。平滑肌瘤呈椭圆形或分叶状,形态规整,边界清楚,呈均匀低回声．肿瘤部位消化道壁结构完整。平滑肌肉瘤瘤体较大,形态不规整,边界不清楚,呈不均匀低回声;有坏死出血时声像图可见液性暗区。神经鞘瘤呈球状,形态规整,边界清楚,由黏膜下层向胃腔外生长,肿物部位黏膜连续完整。经手术病理确诊的25例胃肠道间叶组织源性肿瘤超声检出率为100％．定位诊断准确率为84％．超声定性诊断准确率为68％。结论超声检查对胃肠道间叶组织源性肿瘤的诊断有较大临床应用价值。     

上皮间叶转化及其在间叶源性肿瘤中的研究进展

上皮间叶转化(epithelial mesenchymal transition,EMT)出现在各种生理和病理情况下,参与胚胎发生与器官发育、纤维化过程以及肿瘤的形成和转移.目前的研究使人们对EMT的分子机制有了一定的认识,EMT与肿瘤发生和转移间关系的研究对象较多集中于上皮源性的肿瘤和细胞系,而近年研究发现EMT也存在于间叶源性的肿瘤中,其分子调控机制与在上皮源性肿瘤中可能不同.本文就EMT的分子机制及其在间叶源性肿瘤中的研究进展做一综述.     

大多数引起骨软化症的间质肿瘤是一种独立的病理组织类型

以往认为骨软化症可由多种肿瘤引起，如血管外皮瘤、血管瘤、低度恶性的血管内皮瘤等，但美国Emory大学的Folpe等通过研究认为大多数引起骨软化症(oncogenic osteomalacia)的间质肿瘤是独立的病理组织类型——磷酸盐尿性间质肿瘤，混合结缔组织亚型(phosphaturic mesenchymal tumor，mixed connective tissue variant，PMTMCT)。PMTMCT     

低磷酸盐血症性佝偻病PHEX基因突变分析

目的 鉴定一个低磷酸盐血症性佝偻病家系的致病基因突变.方法 采集患者外周静脉血,提取基因组DNA.PCR扩增PHEX基因22个外显子及外显子/内含子交界区序列,进行DNA测序分析.结果 DNA测序结果表明患儿PHEX基因第20内含子受体位点突变,IVS20-1G＞T.结论 PHEX 基因新剪接突变IVS20-1G＞T导致该家系低磷酸盐血症性佝偻病的发生.

Abstract：

Objective The aim of this study was to identify the disease-causing genetic alteration of PHEX gene in a Chinese hypophosphatemic rickets(HR) family.Methods Genomic DNA was extracted from white blood cells by standard methods. All 22 coding exons and their flanking intronic sequences of PHEX gene were PCR-amplified , purified, and subjected to DNA sequencing.Results We identified an acceptor site mutation IVS20-1G ＞T in PHEX gene in the Chinese HR family.Conclusion This study confirms the relationship between the novel splicing mutation IVS20-1G＞T of the PHEX gene and the clinical findings of this HR family.     

间叶软骨肉瘤10例临床病理分析

目的 探讨间叶软骨肉瘤的临床、影像和病理学特征及病理鉴别诊断.方法 收集间叶软骨肉瘤10例的临床及影像学资料,通过光镜观察及免疫组织化学EnVision法分析其临床、影像学、病理学特征、免疫表型及病理鉴别诊断.结果 10例间叶软骨肉瘤平均年龄28.4岁,男女比8 : 2.发病部位分别为股骨(2例)、肱骨(2例)、椎管内(2例)、椎骨(1例)、髂骨(1例)、大腿软组织(1例)、臀部软组织(1例).影像学表现无特异性改变,以溶骨性骨质破坏为主伴钙化.组织学由高度富于细胞的幼稚间叶小细胞和相对良性的软骨成分相结合,两种成分的分界十分清楚,比例不确定.术前单点穿刺活检漏诊、误诊率高.结论 间叶软骨肉瘤为软骨肉瘤的少见特殊类型,具有与普通软骨肉瘤和小细胞性骨肉瘤不同的临床、影像学和病理学特征,预后差.     

Phosphaturic mesenchymal tumour mixed connective tissue variant: report of three cases with unusual histological findings

Phosphaturic mesenchymal tumour mixed connective tissue variant (PMTMCT) is a rare tumour occurring in bone and soft tissue that usually behaves in a benign manner. Elaboration of biologically active substances by this tumour gives rise to a paraneoplastic syndrome known as oncogenic osteomalacia, manifesting clinically as bone pain, generalized weakness and pathological fractures. Recognition of PMTMCT and its associated syndrome is important, as resection of the tumour in most instances results in prompt resolution of symptoms. Previously reported cases of this tumour have emphasized the consistent presence of certain histological features that are considered prerequisite for making the diagnosis of PMTMCT. We describe three cases of PMTMCT, of which two first presented with progressive symptoms of osteomalacia and one remained clinically silent aside from the symptom of a palpable lump. Our cases highlight the wide-ranging histological patterns displayed by these tumours, and draw attention to certain microscopic findings that until now have been given little if any mention. Tentacular growth pattern and satellite nodules appear to be common findings in PMTMCTs, and can make complete surgical excision of these tumours challenging. The ability of this otherwise histologically benign tumour to permeate vascular spaces has to our knowledge never been described previously. One tumour lacked the characteristic calcifying matrix of PMTMCT, suggesting that in some tumours this defining feature may be focal if not entirely absent. PMTMCT shares features with and can resemble a variety of bone and soft tissue neoplasms, requiring the surgical pathologist to be familiar with this entity.     

Phosphaturic mesenchymal tumor diagnosed by fine-needle aspiration and core biopsy: a case report and review of literature

Oncogenic (tumor-induced) osteomalacia is a rare paraneoplastic syndrome of phosphate wasting that is frequently associated with phosphaturic mesenchymal tumor (PMT). As the cytologic features of this tumor apparently have not been reported, we describe the fine-needle aspiration (FNA) findings for PMT that arose from the gluteal soft tissue in a patient with hypophosphatemia and multiple fractures secondary to osteomalacia. Smears from the computerized tomography (CT)-guided FNA showed groups of spindle cells having elongated nuclei, fine to moderately coarsely granular chromatin, inconspicuous nucleoli, and delicate cytoplasm. Marked nuclear atypia, mitotic figures, and necrosis were absent. The differential diagnosis included a variety of benign and malignant spindle cell neoplasms such as monophasic synovial sarcoma, leiomyoma, peripheral nerve sheath tumor, fibrosarcoma, and, less likely, metastatic melanoma and sarcomatoid carcinoma. The bland-appearing cytologic features of a spindle cell tumor in a patient with osteomalacia should suggest the diagnosis of PMT.     

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.     

Possibility of D2-40 as a diagnostic and tumor differentiation-suggestive marker for some of phosphaturic mesenchymal tumors

Phosphaturic mesenchymal tumor (PMT) has been established as a tumor that causes tumor-induced osteomalacia (TIO) associated with mesenchymal neoplasm. Its lineage of differentiation has not been elucidated. Previously, the presence of lymphatic vessels inside PMTs has been documented using an anti-podoplanin antibody; the tumor cells of PMTs were reported to not react with it. In this study of 14 cases of PMTs, we used immunohistochemistry of D2-40, a relatively specific lymphatic endothelial marker, to see if they stained PMTs or not, with particular interest in its reaction with microcystic structures containing lymph-like fluid. We report that most of the PMTs (12 out of 14 cases; 86%) were immunostained by D2-40 in their tumor cells; D2-40-positive lymphatic vessels inside the tumor were also observed. We used a proportion score (0-4+), an intensity score (0-3+), and a total score (the sum of the proportion score and the intensity score) to quantitate our results. We report that 50% of cases (7 out of 14 cases) had a total score ≥ 4+; immunostaining of D2-40 in cases with a total score ≥ 4+ was easy to observe at a glance. Most of the tumor cells lining the microcystic structures were immunostained with D2-40. Thus, D2-40 could be a useful diagnostic marker of PMTs and it might also indicate that PMTs take a lymphatic endothelial immunophenotype.     

Phosphaturic mesenchymal tumor, mixed connective tissue variant (oncogenic osteomalacia)

A case of tumor-induced phosphaturic osteomalacia in a 54 year old man is reported. The patient was admitted because of progressive muscle spasms with pain and weakness in the bilateral thighs. Laboratory data showed hypophosphatemia, decreased tubular resorption of phosphate (TRP), a low 1,25-dihydroxyvitamin D level, and a high serum alkaline phosphatase level. Radiologic examinations revealed multiple lesions of osteomalacia in the ribs, and a small mass in the lower posterior mediastinum. After removal of the tumor, clinical symptoms disappeared and hypophosphatemia, decreased TRP, and the 1,25-dihydroxyvitamin D level were corrected. Microscopical examination revealed that the tumor was composed of mature adipose tissues, osseous tissues, and primitive stromal zones including osteoclast-like giant cells, non-mineralized woven bone, and various sized blood vessels. Patho-physiologic observations suggested that the tumor secreted some humoral substances inhibiting 25-hydroxyvitamin D-1 alpha-hydroxylase activity, renal phosphate resorption, and parathyroid hormone production.     

Diagnosis of phosphaturic mesenchymal tumor (mixed connective tissue type) by cytopathology

Oncogenic osteomalacia (OO) is a rare paraneoplastic condition in which a bone or soft tissue tumor induces biochemical and clinical signs and symptoms of osteomalacia (or rickets) most often by the production of the phosphaturic protein, fibroblast growth factor-23. Phosphaturic mesenchymal tumor, mixed connective tissue type (PMTMCT) is a rare, histologically distinct tumor that represents the most common cause of OO. As the clinical diagnosis of OO is typically suspected on the basis of clinical and biochemical features and the presence of a bone or soft tissue tumor, cytologic examination might potentially provide the necessary pathologic confirmation of OO. In this case of a 46-year-old female with clinical stigmata of OO and a right distal humeral mass, we report that the fine-needle aspiration findings of short, cytologically bland spindled cells embedded in a fine, fibrillary stromal-rich matrix and the presence of osteoclast-type giant cells associated with the stromal matrix provide strong pathological evidence for PMTMCT and assist in pathologically confirming the clinical impression of OO, thus alleviating the need for a more invasive diagnostic surgical procedure Diagn. Cytopathol. 2012. ? 2011 Wiley Periodicals, Inc.