Sex cord-stromal tumors of the testis

Testicular tumors apart from those in the germ cell family are uncommon and are mostly sex cord-stromal tumors and may pose a major diagnostic challenge. This review focuses on the clinicopathologic features of these uncommon neoplasms, pertinent differential diagnoses, relevant immunohistochemical and molecular findings as well as the recent updates proposed by the World Health Organization (WHO). Contrast between these neoplasms as seen in the male and female gonad will also be made when warranted. The commonest sex cord-stromal tumor of the testis is the Leydig cell tumor which, when seen in children, is often associated with sexual precocity. The histologic features are generally those of an easily recognized oxyphilic neoplasm but various peculiarities such as microcysts and spindling of the tumor cells may case diagnostic difficulty on occasion. In the male, in contrast to the female, the most common sex cord-stromal tumor of epithelial nature is the Sertoli cell tumor. Most of these fall in the not otherwise specified category and are usually characterized by a diagnostically helpful at least focal hollow or solid tubular pattern. Occasional malignant Sertoli cell tumors have a predominantly diffuse pattern sometimes interrupted by septa with a lymphocytic infiltrate that can cause seminoma to be mimicked. Rare Sertoli cell tumors are associated with marked sclerosis. The so-called large cell calcifying Sertoli cell tumor, may be sporadic or associated with manifestations of the Carney syndrome. A distinctive entity referred to as intratubular hyalinizing Sertoli cell neoplasia occurs in the testis of young boys with Peutz-Jeghers syndrome. It is often bilateral, microscopic and associated with gynecomastia. Testicular granulosa cell tumors are much rarer than their ovarian counterparts but can be similarly subdivided into adult and juvenile forms. In the male, the juvenile granulosa cell tumor has a particularly striking tendency to occur in the first 6 months of life. The primitive appearance of the nuclei and brisk mitotic activity of the juvenile granulosa cell tumor may result in a misdiagnosis of a more malignant neoplasm. The histologic spectrum of the adult granulosa cell tumor is as seen in the more common female examples. Pure stromal tumors of the testis are much less common than similar tumors in the ovary and the well-known thecoma is remarkably rare in the testis. Fibromas of stromal derivation in the testis should be distinguished from fibromas that originate from the tunica albuginea and from examples of the non-neoplastic process nodular pseudotumor.     

Uterine tumors resembling ovarian sex cord-stromal tumors: synchronous uterine tumors resembling ovarian sex cord-stromal tumors and ovarian sex cord tumor

Uterine tumors resembling ovarian sex cord-stromal tumors (UTROSCTs) are very rare. In this article, we present 3 cases that manifest classical histomorphological features alongside diverse immunohistochemical findings. As a distinctive finding, one of the patients had UTROSCT in the uterus and an ovarian sex cord tumor, called granulosa cell tumor, in the left ovary, simultaneously. Problems in diagnosing such pathologic condition generally arise because of the variable histologic picture of UTROSCT and may cause problems for general and other nongynecologic surgical pathologists. Immunohistochemically, these tumors express different markers that indicate their polyphenotypic origins.     

Sex cord-stromal tumours of the ovary

The aim of this review is to give a reasonably concise resumé of our knowledge of the sex cord-stromal tumours of the ovary. Lipoid cell tumours of the ovary are often included within this broad category but this poorly defined and heterogenous group of neoplasms will not be considered here. This review is a selective one and no attempt is made to cover all aspects of sex cord-stromal tumours or to provide a complete bibliography. The histological features of many of the neoplasms in this group, particularly those which have been recently defined, are discussed but a consideration of differential histological diagnosis is excluded. The ultrastructural characteristics of the various neoplasms are considered only in terms of their relevance to histogenesis or metabolic activity.     

卵巢黏液性囊腺瘤合并性索-间质肿瘤的临床病理观察

目的 探讨卵巢黏液性囊腺瘤合并性索-间质肿瘤(MCSC)的临床病理特点、组织起源及其诊断和鉴别诊断.方法 对1例MCSC进行组织形态学、免疫组化观察,并复习相关文献.结果 患者发现盆腔肿物1年,无明显不适及内分泌症状.大体上肿瘤为多房囊性,囊内壁可见散在的实性结节,镜检肿瘤由黏液性囊腺瘤和性索间质肿瘤两种成分组成,前者囊壁衬覆良性肠型黏液柱状上皮,性索间质成分瘤细胞呈小管状、条索状、梁状排列,局部有黄素化,两种成分混合存在,未见移行.免疫组化:性索成分瘤细胞呈Melan A弥漫强阳性;αInhibin和CD56局灶阳性;并见CKpan、vimentin、ER及PR的阳性表达;而EMA、CEA、CD99、S-100、CgA、Syn、nestin及SMA均阴性;Ki-67指数小于5%.结论 MCSC是罕见的卵巢肿瘤,性索间质成分可能是黏液性囊腺瘤囊壁内间质的一种反应性增生.诊断时需与类癌、伴异源成分的支持-间质细胞瘤、畸胎瘤等鉴别.     

Investigating differentiation mechanisms of the constituent cells of sex cord-stromal tumours of the ovary

SOX-9, an essential factor for male sexual development, can be induced by prostaglandin D2 in a Sry-independent mechanism. Recent data suggest that the hedgehog pathway is involved in the differentiation of normal Sertoli and Leydig cells. The purpose of our study was to investigate the mechanisms involved in the differentiation of ovarian sex cord-stromal tumour (SCST) cells. Two Sertoli-Leydig cell tumours and two granulosa cell tumours with a minor Sertoli element were studied using immunohistochemistry on paraffin-embedded tissue sections. Sertoli cells expressed anti-Mullerian hormone (AMH), SOX-9, prostaglandin D synthase (Pgds) and bcl-2 (in four of four cases); sonic hedgehog (Shh) and p53 (in three of four cases) and androgen receptors (AR; in one of four cases). Ki-67 index ranged from 10% to 50%. Leydig cells expressed Shh and AR (two of two cases), while they showed no expression of p53, bcl-2 and 0% Ki-67 index. Granulosa cells expressed AMH, Pgds, Shh, estrogen receptors, progesterone receptors, AR and bcl-2 (in two of two cases) and p53 (in one of two cases). Ki-67 index was 10% and 40%, respectively. Further investigation is required to clarify the role of the molecules outlined above in the histogenesis of ovarian SCST, as Pgds-mediated SOX-9 upregulation could provide a reasonable explanation for the presence of testicular differentiation in ovarian SCST.     

具有内分泌功能的卵巢肿瘤

目的探讨具有内分泌功能的卵巢肿瘤的临床病理特征.方法对本院临床表现有内分泌功能并经手术治疗的24例卵巢肿瘤进行临床内分泌表现、组织学类型分析,并行免疫组织化学EnVision二步法染色,抗体为AE1/AE3、上皮膜抗原(EMA)、α-抑制素、Calretini、平滑肌肌动蛋白(SMA).结果 (1)临床内分泌的表现主要为性激素异常, 在幼女或绝经后妇女均有较明显的症状和体征,而在生育年龄妇女则表现的较为隐匿和复杂.(2)肿瘤的组织学类型主要为卵巢性索-间质肿瘤卵巢型13例(颗粒细胞瘤8例,泡膜纤维瘤2例,硬化性间质瘤3例),睾丸型7例(支持细胞瘤1例,支持- Leydig细胞瘤5例,Leydig细胞瘤1例),非特异性类固醇细胞瘤2例;这类肿瘤11例直径<5 cm,4例较大或巨大,最大直径达18 cm;切面多为灰粉黄色,实性或囊实性.另外2例为原发上皮性肿瘤,直径分别为12 cm和14 cm.(3)免疫组织化学染色显示卵巢性索-间质肿瘤α-抑制素全部(22/22)和Calretini绝大多数(18/22)呈阳性表达,组织形态分化好的区域表达强于分化差的区域;2例上皮性肿瘤的间质黄素化细胞也呈阳性表达.SMA在5例泡膜纤维瘤和硬化性间质瘤均呈强阳性表达,部分(3/8)颗粒细胞瘤呈弱阳性表达.部分(6/22)性索-间质肿瘤AE1/AE3阳性表达,但EMA均为阴性.结论具有内分泌功能的卵巢肿瘤多数临床表现为性激素的异常,临床表现与肿瘤的组织学类型不完全一致.其组织学类型主要为性索-间质肿瘤.非性索-间质性卵巢肿瘤也可表现为性激素异常.免疫组织化学染色可协助诊断,并用于与上皮性肿瘤鉴别.     

A CASE OF OVARIAN GRANULOSA CELL TUMOR WITH INVASIVE ADENOCARCINOMA OF THE ENDOMETRIUM. A Case Report and Review of the Japanese Literature

A 47-year-old woman was admitted complaining of irregular uterine bleeding. On surgery, an ovarian tumor was found together with a broad-based polypoid endometrial mass. These lesions were histologically diagnosed as granulosa cell tumor with invasive adenocarcinoma of the endometrium. To our knowledge, only four other cases of granulosa cell tumor with adenocarcinoma of the endometrium have been reported in Japan, although our case was unique in showing invasion to the uterine myometrium. ACTA PATHOL JPN 38: 947∼951, 1988.     

Ovarian Sex Cord Tumor with Annular Tubules: Report of a Case

A 23-year-old woman underwent resection of a tumorous right ovary after long-standing irregular genital bleeding. The tumor measured 50X30 mm and had a yellowish-white solid cut surface with scattered small cysts. The light microscopic diagnosis was a sex cord tumor with annular tubules. Ultrastructurally, the tumor cells had Charcot-Boettcher filaments and showed vimentin positivity by immunohistochemistry. A three-dimensional reconstruction study proved that the tumor cell nests had an ovoid outer margin and contained blind-ended ellipsoid hyaline bodies. This tumor is presumed to be a variant of sex cord/stromal tumor showing differentiation predominantly to Sertoli cells. Acta Pathol Jpn 41: 701–706, 1991.     

Testicular sex cord-stromal lesions: Immunohistochemical analysis of cytokeratin,vimentin and steroidogenic enzymes

Summary We have studied immunolocalization of all steroidogenic enzyme involved in sex steroids biosynthesis, P-450 side chain cleavage (P-450scc), 3 hydroxy steroid dehydrogenase (3-HSD),P-450 17 hydroxylase (P-450₁₄) andP-450 aromatase (P-450arom) and that of vimentin and cytokeratin in 14 cases of testicular sex cord-stromal tumours (6 Leydig cell tumours, 5 Sertoli cell tumours, 2 fibromas and 1 granulosa cell tumour) as well as 4 cases of hyperplasia (2 Leydig and 2 Sertoli). Leydig cell tumour expressed all four steroidogenic enzymes examined, indicating that this tumour can synthesize oestrogen from cholesterol. In 2 cases of Sertoli cell tumour, the tumour cells with clear cytoplasm and without Reinke's crystals expressedP-450_ssc, 3-HSD andP-450₁₇, suggesting the capability of androgen production in these tumour cells. Fibromas and granulosa cell tumour were negative for the enzymes examined. In immunohistochemistry of intermediate filaments, Leydig cell tumours demonstrated only vimentin. Sertoli cells in hyperplasia and non-neoplastic testis expressed only vimentin but Sertoli cell tumours expressed both cytokeratin and vimentin. Cytokeratin immunoreactivity was correlated with morphological epithelial differentiation in Sertoli cell tumour. These findings in testicular Sertoli cell tumour are considered to represent the multiple differentiation capacity of this neoplasm. Immunohisto-chemical study of steroidogenic enzymes and intermediate filaments provided new insight into neoplastic steroidogenesis and the differentiation capacity of testicular sex cordstromal neoplasms.     

No evidence of endometriosis within serous and mucinous tumors of the ovary

Ovarian endometriosis can transform into malignant tumors. The author retrospectively examined HE slides of 112 serous tumors and 75 mucinous tumors for the existence of ovarian endometriosis. When endometriosis is present within the tumors, the term "endometriosis-derived tumor" was applied. When endometriosis is recognized adjacent to the tumor, the term "endometriosis-associated tumor" was used. Of the 112 serous tumors (46 benign, 18 borderline, and 50 malignant), 4 (3.5%) (2 benign and 2 malignant) were endometriosis-associated tumors. None was endometriosis-derived tumor. Of the 75 mucinous tumors (30 benign, 26 borderline, and 19 malignant), 4 (5%) (1 borderline and 3 benign) were endometriosis-associated tumors. No tumors showed endometriosis-derived tumors. The data suggest that endometriosis does not transform into serous and mucous tumors. The author felt the limitation of retrospective survey, because the limited numbers of slides (5 to 15) were obtained from each tumor. The author also felt that endometriosis can be difficult to discern because of degenerative changes and other similar lesions such as fallopian tube, fimbria, inclusion cysts, rete ovarii, paraovarian cyst, and Müllerian ducts remnants. Prospective study using whole ovarian examination is required.     

干细胞相关因子在大鼠卵巢颗粒细胞中的表达

背景：现有研究表明,人与大鼠卵巢优势卵泡中的颗粒细胞具有表达干细胞特性的现象。 目的：探讨干细胞相关因子在大鼠卵巢颗粒细胞中的表达。 方法：将大鼠卵巢组织制作石蜡切片后,使用免疫组化法检测CD34,CD133,ABCG2/Bcrp1,Pou5f1/Oct-4的表达。卵泡穿刺法获取颗粒细胞,并使用免疫组化法检测FSHR受体的表达以鉴定颗粒细胞的纯度。免疫组化法检测颗粒细胞CD44,C-Kit的表达情况,RT-PCR检测卵巢组织与颗粒细胞ABCG2/Bcrp1、Pou5f1/Oct-4、Nanog基因的表达情况。 结果与结论：免疫组化法石蜡切片显示部分卵巢颗粒细胞CD34,CD133,ABCG2/Bcrp1,Pou5f1/Oct-4阳性表达,而Pou5f1/Oct-4蛋白的表达在卵泡发育的周期中逐步增多,并在黄体化的时候显著增强,形成白体后则消失,因而具有周期性表达的特点。卵泡穿刺法提取的原代颗粒细胞FSHR受体鉴定阳性率在95%以上。体外培养的颗粒细胞以长梭形或菱形为主,部分细胞有聚集生长现象,且CD44,C-Kit阳性表达。RT-PCR检测结果显示,卵巢组织与体外培养的颗粒细胞均不表达Nanog,卵巢低表达Pou5f1/Oct-4,强烈表达ABCG2/Bcrp1,颗粒细胞微弱表达Pou5f1/Oct-4,而ABCG2/Bcrp1表达较强。以上结果显示大鼠卵巢中的部分颗粒细胞具有干细胞的特性。中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程全文链接：     

CT在外突性子宫肌瘤与卵巢性索间质肿瘤的鉴别诊断价值

目的:探讨CT对外突性子宫肌瘤与卵巢性索间质肿瘤的鉴别诊断价值。方法:回顾性分析2015年1月~2019年2 月重庆医科大学附属第一医院收治的外突性子宫肌瘤（n=43）和卵巢性索间质肿瘤（n=36）患者资料。分析CT平扫及增 强图像，将数据传输至ADW4.5工作站完成多平面重建、最大密度投影和容积再重建等CT后处理重建。观察并记录肿瘤 与输尿管位置、肿瘤供血动脉、卵巢静脉与肿瘤关系、肿瘤强化程度及方式、有无腹水。以病理结果为金标准，计算CT诊 断准确率。结果:外突性子宫肌瘤位于输尿管前或内前方，主要由子宫动脉供血，分支多且于瘤体内呈较均匀分布，肌瘤 实性部分呈漩涡样中度或明显强化改变，追踪卵巢静脉可见正常卵巢组织，不易合并腹水；卵巢性索间质肿瘤位于输尿管 前或内前方，主要由卵巢动脉供血，分支少且于肿瘤实质内呈较均匀分布，静脉期见卵巢血管蒂征，肿瘤实性部分呈无或 轻度强化改变，追踪卵巢静脉不能显示正常卵巢组织，常合并腹水，可见卵巢血管蒂征。以病理结果为金标准，术前CT诊 断外突性子宫肌瘤准确率为93.03%，术前CT诊断卵巢性索间质肿瘤准确率为80.56%。结论:根据CT特点并结合临床 表现可较好地对外突性子宫肌瘤与卵巢性索间质肿瘤做出鉴别诊断，值得临床推广应用。     

Endocervical-like mucinous borderline tumors of the ovary: clinicopathological features and electron microscopic findings

Endocervical-like mucinous borderline tumor (EMBT) is a distinct entity of the ovary that seems to be underrecognized. It occurs with relatively high frequency in Japanese women. Compared with intestinal-type mucinous borderline tumor (IMBT), more frequent bilateral occurrence, paucilocular cysts, association with endometriosis, absence of pseudomyxoma but possible association of peritoneal implants and lymph node metastases, and lower mortality rate are the characteristic features. Histologically, it consists of a mixture of two types of epithelium, tall columnar mucinous cells and stratified eosinophilic cells. Electron microscopy revealed that they were endocervical glandlike mucinous cells and ciliated columnar epithelium reminiscent of the fallopian tube. As the mixture of EMBT and serous borderline tumor (seromucinous borderline tumor) occurs, these findings may show that the tumor shows MÜllerian origin with two-way differentiation, or differentiation toward endocervical glands with metaplastic features as seen in reactive endocervical lesions.     

Giant cell tumor of the ovary

Summary A 31 year old woman with primary sterility was found, at operation, to have endometriosis of the Fallopian tubes and a giant cell tumor of the ovary, histologically indistinguishable from giant cell tumor of bone. The tumor is considered to be primary and benign, with a follow-up period of 4 1/2 years and no signs of recurrence or malignancy.     

The STK11/LKB1 Peutz-Jegher gene is not involved in the pathogenesis of sporadic sex cord-stromal tumors, although loss of heterozygosity at 19p13.3 indicates other gene alteration in these tumors

Germ line mutations in the STK11/LKB1 tumor-suppressor gene (chromosome 19p13.3) are responsible for the Peutz-Jeghers syndrome (PJS). PJS patients frequently develop neoplasms of various organs. Ovarian sex cord-stromal tumor (SCST) with annular tubules, which shows a characteristic morphology intermediate between granulosa cell and Sertoli cell tumors, is distinctively associated with PJS. Although somatic mutations of STK11 are reportedly rare in sporadic forms of common cancers linked to PJS, there are no available studies assessing STK11 alterations in larger series of sporadic ovarian tumors with granulosa, Sertoli or combined differentiation. We examined 29 sporadic SCSTs for loss of heterozygosity (LOH) at 19p13.3, mutation, and promoter methylation of STK11. LOH at 19p13.3 was detected in 12 of 29 (41%) SCSTs, with the highest frequency at chromosome marker D19S894, which localizes approximately 3 mb centromeric to STK11, and it was more frequent in granulosa/Sertoli-stromal cell tumors (10 of 19; 52%) than in thecoma-fibroma tumors (2 of 10; 20%). The 2 fibrothecomas harboring LOH contained sex cord elements. None of the LOH-positive SCSTs demonstrated mutations or promoter methylation of STK11. Our results indicate that LOH at 19p13.3 in sporadic SCSTs targets a gene different from STK11, and may play a role in the pathogenesis of sporadic SCSTs, especially in tumors containing sex cord derivatives.     

卵巢幼年型粒层细胞瘤的临床病理分析

目的 分析卵巢幼年型粒层细胞瘤的临床病理特点,探讨其诊断标准、特殊形态及预后因素等.方法 对7例幼年型粒层细胞瘤的临床资料行回顾性分析总结、组织切片进行形态观察,对其中6例行免疫组织化学EliVision法染色.6例进行了随访.结果 7例幼年型粒层细胞瘤的平均年龄为24岁(6～53岁).5例有性激素紊乱的临床表现,2例以腹胀及腹痛为主要症状.除1例(例2)行全子宫和双附件切除,其余6例均为一侧附件切除.5例Ⅰ A期,2例Ⅰ C期.6例随访病例中除1例(例1)术后1年余死于肿瘤转移,其余5例健在,随访时间平均4.3年(1～10年).肿瘤最大径7～20 cm(平均13.4 cm),4例囊实性,2例单房囊性,1例实性.镜下全部为弥漫生长和不典型滤泡样结构,未见Call-Exner小体.肿瘤细胞核小、较圆、深染,极少见核沟,3例重度异形,1例中度,3例轻度.1例(例2)小灶有成年型粒层细胞瘤特征.5例核分裂象＞5/10 HPF,2例核分裂象不易见.6例CK(AE1/AE3)阴性、波形蛋白强阳性;1例α-抑制素阳性;4例CD99阳性、Calretinin阴性.结论 幼年型粒层细胞瘤以不典型滤泡样结构而非Call-Exner小体为结构特点,以核小、圆形、深染而无核沟为主要细胞学特点,以大多数CK阴性和波形蛋白阳性为特殊免疫表型,兼以有少量成年型粒层细胞肿瘤结构及单房囊性肿瘤为其特殊形态.肿瘤破裂可能是影响预后的一个重要因素,核异形、核分裂象多见及肿瘤体积大并不能提示肿瘤具有恶性潜能.