Phosphaturic mesenchymal tumor (mixed connective tissue variant): a case report with spectral analysis

We present a further case of a rare mesenchymal neoplasm termed phosphaturic mesenchymal tumor (mixed connective tissue variant). The patient was a 42-year-old man with a long history of osteomalacia of unknown etiology with pathological bone fracture, abnormality of parathyroid glands, kyphosis, scoliosis, and spondylosis. Laboratory investigation disclosed hypophosphatemia, elevated serum alkaline phosphatase activity, and normal serum calcium level. The patient had a soft tissue mass in the right inguinal area, measuring 11×6×5 cm, which was previously interpreted as a calcified hematoma on sonography. The tumor was surgically removed. Grossly, the tumor was well circumscribed, unencapsulated, and had soft to dense consistency. The cut surface had a variegated appearance due to the presence of large hemorrhagic areas admixed with foci of grey-yellow tissue. Histologically, the tumor was composed of primitive mesenchymal cells, osteoclast-like cells, and cells showing myofibroblastic features without cytologic atypia. There were a well developed vascular network, microcystic areas, and poorly formed cartilaginous foci. Unusual and hitherto unpublished prominent features were flower-like, slate-gray crystals, widespread hemosiderin deposits and large areas of hemorrhages, with the latter comprising approximately 60% of the tumor. A spectral analysis indicated that chemically, the crystals mainly consisted of calcium phosphate and sodium nitrate.     

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.     

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.     

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.     

软组织磷酸盐尿性间叶肿瘤的临床病理分析

目的研究磷酸盐尿性间叶肿瘤（混合结缔组织亚型）的临床与病理学特点。方法对1例骨软化症患者的肿块切除标本进行光镜、电镜和免疫组化SP法检测。结合临床资料,并复习相关文献。结果患者表现为顽固性骨软化症、低磷酸盐血症,高磷酸盐尿,高血清碱性磷酸酶,外周血单核细胞增多,血钙浓度正常。经99mTc—OCT（奥曲肽）检查指导临床发现左胭窝区小肿块并切除之。术后3天,血磷恢复正常。光镜下肿瘤主要由肥胖的梭形细胞和破骨细胞样多核巨细胞构成,具有丰富的血管,可见血管外皮瘤样血管、散在脂肪岛、明显的出血及含铁血黄素沉积,肿瘤边缘有不完整的膜状骨样或软骨样组织。电镜下见梭形细胞内含数量不等的细颗粒状电子致密物,其中部分为结晶样高电子致密度颗粒。免疫组化显示多核细胞和单核间质细胞CD68阳性。结论该例为肿瘤源性骨软化症,其病理类型为磷酸盐尿性间叶肿瘤,混合结缔组织亚型。外科切除后治愈,99mTc-OCT对于指导临床发现小的隐蔽病灶很有价值。     

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.     

CD56 may be a more useful immunohistochemical marker than somatostatin receptor 2A for the diagnosis of phosphaturic mesenchymal tumors

Phosphaturic mesenchymal tumors (PMTs) are the most typical cause of tumor-induced osteomalacia (TIO) associated with mesenchymal neoplasms. Specifically, TIO is attributed to the production of phosphatonins, such as fibroblast growth factor 23 (FGF23), participating in the homeostasis of phosphate. Although immunohistochemistry (IHC) for FGF23 showed characteristic positive staining in PMTs, FGF23 antibodies that can be used for the reliable diagnosis of PMTs are hard to obtain in common pathology laboratories. Somatostatin receptor 2A (SSTR2A) has been previously proposed as an alternatively useful marker for the diagnosis of PMTs. However, SSTR2A is not commonly utilized in pathological laboratories. The CD56 marker is a useful alternative that is comparable to SSTR2A and is similar considering the sensitivity. Even in cases of PMTs originating in the bones, ethylenediaminetetraacetic acid-based decalcification for tissue processing does not seem to affect the IHC of CD56. As CD56 immunopositivity in mesenchymal tumors is limited, it also has some degree of specificity for PMTs. Thus, when PMTs are suspected, the use of CD56 is recommended.     

Lymphatic vessels are present in phosphaturic mesenchymal tumours

Oncogenic osteomalacia (OO) is an acquired form of hypophosphataemic osteomalacia, which is associated most commonly with the development of a benign phosphaturic mesenchymal tumour mixed connective tissue type (PMTMCT). PMTMCTs are generally well vascularised tumours, and many have in the past been classified as haemangiomas and haemangiopericytomas. Although these tumours show some morphological variation, it has been proposed that they represent a distinct histopathological entity. Our aim in this study was to determine by immunohistochemistry the vascular profile of PMTMCT. Using monoclonal antibodies directed against several vascular markers, including the lymphatic endothelial cell antigens LYVE 1 and podoplanin, we found that PMTMCTs, in contrast to haemangiomas and haemangiopericytomas, contain lymphatic vessels. Taken with previous observations that PMTMCTs overexpress FGF23 and other gene products, this finding provides further evidence that most osteomalacia associated mesenchymal tumours represent a discrete pathological entity.     

Benign mixed epithelial and stromal tumor of the kidney (MEST) with cytogenetic alteration

Benign mixed epithelial and stromal tumor of the kidney (MEST) is a new, rare entity. These tumors are composed of two components: a stromal and an epithelial one. Clinical outcome is usually good, no specific cytogenetic alterations have been described up to now. We describe for the first time a case with translocation t (1; 19).     

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。     

Primitive myxoid mesenchymal tumor of infancy: report of two cases and review of the literature

Primitive myxoid mesenchymal tumor of infancy is a recently recognized soft tissue tumor with only a few cases reported. Here, we reported another two cases of the lesion, a 5-month-old boy presenting with a soft tissue mass in the neck region that recurred 2 months later and a 3-day-old girl with a congenital superficial dorsal lumbar mass that extended to the spinal canal 1 month later. They shared similar histological patterns, such as unusual diffuse myxoid background, delicate vascular network, small cystic spaces, low to moderate cellularity, and primitive mesenchymal tumor cells. Immunohistochemically, the tumor cells showed positive for vimentin, CD99, CD117 and nestin, negative for myoid, lipoblastic, histiocytic, and neural markers. In conclusion, primitive myxoid mesenchymal tumor of infancy is a distinctive entity with its own clinical pathological features. Expression of CD99, CD117 and nestin may be consistent with the primitive nature of the tumor and may serve as ancillary markers for differential diagnosis from the other infantile tumors.     

Clinical,morphological and immunohistochemical analysis of 13 cases of phosphaturic mesenchymal tumor - A holistic diagnostic approach

BackgroundPhosphaturic mesenchymal tumor-mixed connective tissue (PMT-MCT) is a rare tumor characterized clinically by presence of tumor-induced osteomalacia (TIO), subsequent to elevated fibroblastic growth factor 23 (FGF23) levels. This study aims to analyse the morphological spectrum of PMT along with clinico-pathological correlation and immunophenotype profile of this rare tumor.Materials and methodsDetailed histological analysis of all tumors presenting with TIO over past 7 years was done retrospectively. Immunohistochemistry was performed in all cases for SATB2, STAT6, CD34, FGF23, ERG, S100 and smooth muscle actin (SMA).ResultsA total of 13 cases were analysed (8 female and 5 male) with mean age of 39.8 years. Five cases were arising from bone while 4 each from soft tissue and nasal cavity/paranasal sinus. All presented with hypophosphatemia, hyperphosphaturia, elevated serum FGF23 and features suggestive of osteomalacia. Histological examination revealed basophilic ‘grungy’ calcification seen in 7 (53.8%), osteoid formation in 8 (61.5%), chondroid matrix in 4 (30.8%), adipose tissue in 6 (46.2%), osteoclast-like giant cells in 9 (69.2%) and hemangiopericytomatous (HPC like) blood vessels in 7 cases (53.8%). HPC like vessels and adipose tissue were more common in nasal tumors while calcification was more common in tumors arising from bone. All cases showed immunoreactivity for SATB2 and clinical improvement following resection except one case with residual tumor.ConclusionPMT shows varied histological pattern with various matrix components depending on the site of the tumor. Serum FGF-23 is a useful adjunctive marker for diagnosis.     

枣庄地区200例原发闭经患者的细胞遗传学分析

目的探讨原发闭经患者与细胞染色体异常的关系。方法选择在我院就诊的原发闭经患者200例,对每例患者进行外周血培养、染色体核型分析和妇科检查。结果在200例原发闭经患者中,检查出核型异常90例,异常核型检出率为45%（90/200）。在检出的异常核型中,Turner综合征患者48例,占53.3%（48/90）;46,XY 19例,占21.1%（19/90）;嵌合体/染色体结构异常23例,占25.6%（23/90）。结论性染色体结构或数目异常,可导致患者身材矮小、性腺发育不全、两性畸形、不孕、闭经等临床表现。通过细胞染色体核型分析,不仅为原发闭经患者寻找病因提供了理论依据,而且有利于对患者的治疗进行科学指导。     

体外模拟肿瘤微环境中致大鼠MSCs瘤化因子分析

 目的 探讨模拟肿瘤微环境中骨髓间充质干细胞（MSCs）肿瘤转化的发生与HGF、IL-6、BFGF关系。方法 实验组为C6胶质瘤与MSCs间接共培养模拟肿瘤微环境下MSCs的生长,对照组为星型胶质细胞与MSCs间接共培养模拟正常微环境下MSCs的生长,空白对照组MSCs单独培养;QPCR,免疫荧光检测各组的P53和MDM2的基因和蛋白的表达;ELISA检测各组HGF、IL-6、BFGF的表达;免疫荧光检测对应升高的细胞因子作用于MSCs后的STAT3蛋白的表达。结果 实验组的MSCs形态肿瘤化;MSCs的MDM2 mRNA是对照组的1.56±0.21(P<0.05),MDM2蛋白表达率比对照组升高90±7%(P<0.01);MSCs的P53的mRNA表达是对照组的0.55±0.10, 而P53突变蛋白表达率比对照组升高87±5%(P<0.01);HGF、IL-6水平比对照组中达水平升高(P<0.05);过量IL-6处理组的MSCs的STAT3激活蛋白表达率比正常量IL-6处理组明显升高(P<0.01)。结论 IL-6参与MSCs在肿瘤微环境下的肿瘤转化的发生。