免疫组化标记在子宫间质肿瘤诊断中的应用价值

目的探讨免疫组化标记在子宫间质肿瘤中的表达及诊断价值。方法采用免疫组化S-P法对21例子宫内膜间质肿瘤、8例子宫平滑肌肿瘤、5例子宫内膜腺癌、4例腺肌瘤及6例正常子宫内膜标本进行CD10及SMA、desmin、cK(pan)等相关标记检测。结果16例(76．19％)子宫内膜间质肿瘤CD10呈弥漫表达，5例(23．81％)呈散在灶性表达。平滑肌肿瘤SMA和desmin呈弥漫阳性。结论cD10在子宫内膜间质及间质肿瘤中100％表达，是诊断子宫间质肿瘤比较特异抗体。子宫间质肿瘤可向平滑肌等多个方向分化而表现出多种抗原表达，除了用CD10来确定细胞特性外，结合SMA、desmin等标记可增加其特异性。     

Myxoid endometrial stromal sarcoma of the uterus

A rare case of a myxoid type of endometrial stromal sarcoma of the uterus in a 41-year-old woman is reported. A tumor was found in the myometrium and was well circumscribed, measuring 9 x 7 x 7 cm in size. The tumor was mainly composed of a hypocellular area with tumor cells separated by prominent myxoid stroma. The tumor cells were spindle-shaped and resembled endometrial stromal cells. Numerous small thin-walled vessels were seen throughout the tumor. Immunohistochemically, the tumor cells were diffusely stained for estrogen and progesterone receptors and CD10, and focally and weakly for HHF35, alpha-smooth muscle actin and desmin, but not stained for h-caldesmon. These results indicated that the tumor originated from endometrial stromal cells. The tumor had an increased mitotic activity (MIB-1 labeling index: 1-10%), and focally showed nuclear pleomorphism. Thus, this tumor had a malignant potential and was diagnosed as a myxoid type of low-grade endometrial stromal sarcoma. The patient is currently well with no evidence of local recurrence or metastasis 21 months after the operation. This case indicates a wide morphological spectrum of endometrial stromal tumor. A myxoid endometrial stromal sarcoma should be considered in the different diagnosis of the intramural myxoid tumors in the uterus.     

Myxoid mixed low-grade endometrial stromal sarcoma and smooth muscle tumor of the uterus. Case report

We report the case of a 73-year-old female with myxoid mixed low-grade endometrial stromal sarcoma and smooth muscle tumor of the uterus. Grossly, the tumor sized 130 x 130 x 100 mm involved the uterine corpus almost in its entirety. Histologically, the tumor consisted of two cell types. In some areas, the tumor cells showed typical features of endometrial stromal tumors and resembled stromal cells of proliferative endometrium. In other areas, however, the tumor showed smooth muscle features and consisted of larger mostly epitheloid cells with a moderate amount of cytoplasm. In all areas, myxoid changes and multiple hyalinizing giant rosettes were present. The tumor infiltrated the myometrium in a pattern typical of low-grade endometrial stromal sarcoma. Immunohistochemically, the tumor cells showed expression of vimentin, estrogen and progesterone receptors and variable expression of CD10, α-smooth muscle actin, desmin, h-caldesmon, and cytokeratin AE1/AE3. Other markers examined including CD99, α-inhibin, cytokeratin CAM5.2, S-100 protein, and HMB45 were negative. To the best of our knowledge, mixed low-grade endometrial stromal and smooth muscle tumor with myxoid changes has not been described to date.     

子宫高度富于细胞平滑肌瘤与内膜间质肿瘤的形态学和免疫组织化学对比研究

目的 探索鉴别子宫高度富于细胞平滑肌瘤与子宫内膜间质肿瘤的形态和免疫组织化学特点及其在鉴别诊断中的意义。方法 采用光镜观察和免疫组织化学EnVision法染色对20例子宫高度富于细胞平滑肌瘤,21例内膜间质肿瘤和1例间质肌瘤进行组织病理学分析。结果 高度富于细胞平滑肌瘤肿瘤细胞致密,细胞呈圆形,梭形,胞质少,与邻近的正常肌壁平滑肌细胞有移行,所有病例都可见到成束分布的肿瘤细胞灶,大的厚壁血管明显可见,部分病例中可见裂隙,子宫内膜间质肿瘤肿瘤细胞则与增生期子宫内膜的间质细胞非常相似,螺旋状小动脉散布其间,20例低度恶性间质肉瘤肿瘤组织呈舌状侵入邻近肌壁,免疫组织化学显示高度富于细胞平滑肌瘤h-caldesmon,calponin,CD10,结蛋白及平滑肌肌动蛋白（SMA）的阳性率分别为80.0%(16/20),100%(20/20),0(0/20),95.0%(19/20)及100%（20/20）。而子宫内膜间质肿瘤相应的阳性率则为4.7%(1/21),23.8%(5/21),66.7%(14/21),23.8%(5/21)及19.0%(4/21),这些抗体在两组肿瘤间的表达差异有显著性（P=0.001)。结论 子宫高度富于细胞平滑肌瘤具有特殊形态特点,免疫组织化学h-caldesmon,calponin,CD10,结蛋白及SMA染色有助于其与子宫内膜间质肿瘤的鉴别诊断。     

Endometrial stromal tumors: an update on a group of tumors with a protean phenotype

Endometrial stromal tumors are reviewed with emphasis on their wide morphologic spectrum and problems in differential diagnosis, highlighting issues that have received particular attention in the recent literature. These neoplasms are divided into two major categories--endometrial stromal nodules and endometrial stromal sarcomas--a distinction made on the basis of the lack of significant infiltration at the periphery of the former. The division of endometrial stromal sarcomas into low-grade and high-grade categories has fallen out of favor and the designation endometrial stromal sarcoma is now considered best restricted to neoplasms that were formally referred to as "low-grade" stromal sarcoma. Endometrial sarcomas without recognizable evidence of a definite endometrial stromal phenotype, designated poorly differentiated "endometrial sarcomas," are almost invariably high grade and often resemble the mesenchymal component of a malignant mullerian mixed tumor. Two features of endometrial stromal tumors that may cause confusion are smooth muscle differentiation and epithelial patterns. Cases in the former category often have a characteristic "starburst" pattern of collagen formation. The most common epithelial patterns resemble those seen in ovarian sex-cord stromal tumors. Much less common is endometrioid gland differentiation. Some endometrial stromal tumors have a prominent fibrous or myxoid appearance and the myxoid tumors should be distinguished from myxoid leiomyosarcoma. Other unusual features of endometrial stromal tumors are also discussed. Lesions in the differential diagnosis of uterine endometrial stromal neoplasms include highly cellular leiomyoma, cellular intravenous leiomyomatosis, adenomyosis with sparse glands, metastatic carcinoma, and lymphoma. Endometrial stromal sarcomas at extrauterine sites may be primary or metastatic from a uterine tumor, the latter sometimes being occult and difficult to definitively establish, particularly if there is a history of a remote hysterectomy for "leiomyomas." Endometrial stromal sarcomas of the ovary, whether primary or metastatic, may be difficult to distinguish from ovarian sex-cord stromal tumors. Extragenital endometrial stromal sarcomas may be confused with diverse lesions such as gastrointestinal stromal tumors, hemangiopericytoma, lymphangiomyomatosis, or mesenchymal cystic hamartoma of the lung. Immunohistochemistry may play a role in evaluating these tumors and in some instances establishing the diagnosis although conventional light microscopic analysis suffices in the majority of cases. The unusual tumor, the "uterine tumor resembling an ovarian sex-cord tumor," is also considered in this review as it is almost certainly of endometrial stromal derivation in many cases. These neoplasms may have a striking resemblance to granulosa cell tumors or Sertoli cell tumors, including those with a retiform pattern, and have recently been shown to be frequently inhibin positive.     

Gastrointestinal stromal tumor presenting as a recurrent vaginal mass

Gastrointestinal stromal tumors are CD117 (c-Kit)-positive mesenchymal neoplasms with histologic and ultrastructural features of the interstitial cell of Cajal. While tumors outside of the gastrointestinal tract have been described, to our knowledge the case we present is the first such case in the vagina. We describe a 75-year-old woman with a recurrent vaginal gastrointestinal stromal tumor without apparent rectal involvement. This tumor was characterized by short intersecting fascicles of spindled cells, focal necrosis, and 12 to 15 mitoses per 50 high-power fields. Immunohistochemistry revealed diffuse cytoplasmic positivity for CD117 (c-Kit), CD34, vimentin, and h-caldesmon. Tumor cells were negative for S100, desmin, actin, and CAM 5.2. The differential diagnosis in this case included a vaginal smooth muscle tumor. While histologically similar to a smooth muscle neoplasm, the immunohistochemical profile ruled out smooth muscle differentiation. Gastrointestinal stromal tumor should be considered in the differential diagnosis of vaginal mesenchymal neoplasms.     

Mixed tumors of the vagina: an immunohistochemical study of 13 cases with emphasis on the cell of origin and potential aid in differential diagnosis.

Mixed tumors of the vagina (MTsV) are rare benign neoplasms characterized by an admixture of well-differentiated epithelial cells and stromal-type cells in various proportions. In contrast to mixed tumors in other anatomic sites, the histogenesis of the vaginal tumors is unclear. We studied the immunohistochemical profile of 13 examples to explore their histogenesis and determine whether their immunohistochemical profile might be useful in the differential diagnosis. The panel of antibodies used and the number of cases studied were: AE1/3 (12), cytokeratin 7 (CK7) (13), cytokeratin 20 (CK20) (13), epithelial membrane antigen (EMA) (13), muscle actin (MA) (12), desmin (11), h-Caldesmon (13), CD10 (13), CD34 (11), CD99 (8), and S-100 (7). Eight out of 12 tumors were positive for AE1/3, 7/13 for CK7, 2/13 for CK20, and 6/13 for EMA. MA was positive in 11/12 mixed tumors, desmin in 10/11 tumors and h-Caldesmon in 5/13. All tumors were extensively positive for CD10; CD34 was positive in 7/11; and none out of eight tumors showed membranous CD99 staining. Focal S-100 immunoreactivity was seen in 1/7 tumors. These results show that MTsV coexpress epithelial and mesenchymal markers. The expression of muscle actin (usually extensive), and focal desmin and h-Caldesmon positivity suggests the presence of a smooth muscle or myoepithelial component; however, the S-100 negativity and diffuse CD10 expression argue against it. Positivity for muscle markers does not help distinguish MTsV from smooth muscle or skeletal muscle tumors. The frequent expression of CD10 negates its use in the differential diagnosis with endometrial stromal tumors, and the CD10 and CD34 expression suggests that mixed tumors may arise from a primitive pluripotential cell. MTsV are positive for h-Caldesmon and CD10, two markers that have been used in gynecologic pathology primarily to aid in establishing the smooth muscle or endometrial stromal phenotype of a neoplasm.     

CD10 is a sensitive and diagnostically useful immunohistochemical marker of normal endometrial stroma and of endometrial stromal neoplasms

AIMS: The CD10 antigen is expressed in acute lymphoblastic leukaemia and follicle centre cell lymphoma. A recent study investigating the expression of CD10 in a wide range of non-haematopoietic neoplasms found positive staining in a small number of endometrial stromal sarcomas as well as in normal endometrial stroma. The present study aimed to ascertain whether CD10 positivity is indeed found in normal endometrial stroma and endometrial stromal neoplasms. Staining of a range of tumours which can be confused morphologically with endometrial stromal neoplasms was also undertaken to ascertain whether antibodies against CD10 are of value in a diagnostic sense. METHODS AND RESULTS: Neoplasms included in the study were endometrial stromal nodule (n=1), low-grade endometrial stromal sarcoma (ESS) (n=13), high-grade ESS (n=6), mixed endometrial stromal-smooth muscle tumour (n=1), uterine cellular leiomyoma (n=10), uterine leiomyosarcoma (n=5), adult granulosa cell tumour (AGCT) (n=10), undifferentiated endometrial carcinoma (n=6), uterine carcinosarcoma with an endometrial stromal component (n=1) and type II uterine mesenchymal tumour with sex cord-like elements (n=1). Cases of proliferative (n=5), secretory (n=5) and atrophic (n=3) endometrium were also stained. There was positive staining of stroma but not of glands in all cases of non-tumorous endometrium. There was positive staining of the endometrial stromal nodule and of all low-grade ESS. Staining in these varied but was often diffuse and of moderate to strong intensity. There was positive staining of four of six high-grade ESS, but this was usually focal. There was also positive staining of the endometrial stromal component in the mixed endometrial stromal-smooth muscle tumour and in the uterine carcinosarcoma. Most cellular leiomyomas were completely negative although three exhibited weak positivity. There was some positivity, usually focal or weak, of three of five leiomyosarcomas. Most AGCT and undifferentiated carcinomas were completely negative although one case of each exhibited focal staining. There was focal staining of the type II uterine mesenchymal tumour with sex cord-like elements. CONCLUSION: CD10 is a reliable and sensitive immunohistochemical marker of normal endometrial stroma. Positivity, which is often strong and/or diffuse is found in endometrial stromal nodules and low-grade ESS. Positive staining with CD10, when strong and diffuse, may be useful in distinguishing these tumours from histological mimics, especially cellular leiomyoma and AGCT which are generally negative. In this situation, CD10 should be used as part of a panel which might include desmin and alpha-inhibin depending on the differential diagnosis considered. Positive staining with CD10 in a high-grade uterine sarcoma which is negative with muscle markers might indicate endometrial stromal differentiation and identify a group of neoplasms which it is correct to diagnose as high-grade ESS rather than undifferentiated uterine sarcoma.     

Immunohistochemistry as a diagnostic aid in the interpretation of unusual mesenchymal tumors of the uterus.

Sixty-three pure mesenchymal tumors of the uterus were studied to explore the value of immunostaining in the diagnosis of unusual mesenchymal tumors encountered in the uterus, some not reported previously. Each tumor was evaluated using a panel of immunostains including actin, desmin, vimentin, S-100 protein, and cytokeratin. The final classification, which incorporated the immunohistochemical findings, resulted in the identification of 33 relatively common pure mesenchymal tumors (13 benign and malignant endometrial stromal tumors and 20 benign and malignant smooth muscle tumors) and 30 uncommon tumors (five leiomyosarcomas with osteoclastic giant cells, two xanthomatous leiomyosarcomas, one melanotic schwannoma, one pure rhabdomyosarcoma, one neurofibroma, five plexiform tumorlets, and 15 combined smooth muscle-stromal tumors). The normal endometrial stroma, present in 14 cases, invariably showed a negative reaction for all antibodies. With rare exceptions, the pure endometrial stromal tumors displayed a negative immunoreaction for all antibodies utilized, while the pure smooth muscle tumors consistently showed a positive reaction for actin. Only the two tumors of neural origin (a neurofibroma and a melanotic schwannoma) reacted with S-100 protein. Immunostaining influenced most the final classification of neoplasms initially interpreted as uterine tumors with a sex-cord stromal pattern, endometrial stromal tumors that diverged from the classic lesions by having a spindle cell component, and intravascular leiomyomas with areas of compact proliferation of small round cells with prominent vascularity. All tumors in these three groups were reclassified as combined smooth muscle-stromal tumors following immunohistochemical studies.(ABSTRACT TRUNCATED AT 250 WORDS)     

Myxoid leiomyoma of the vulva mimicking aggressive angiomyxoma

A case of vulvar leiomyoma with extensive myxoid change in a 40 year old female is described. The tumor had a unique connection with a non-degenerative leiomyoma that compressed the rectum and the bladder. Scattered smooth muscle cells in a loose myxoid stroma were immunoreactive for desmin. Fibroblast-like spindle cells were immunoreactive for vimentin but not for desmin. The initial, although incorrect, pathological diagnosis of the tumor was aggressive angiomyxoma based on the similarity in both clinical and pathological aspects with this more invasive tumor. Myxoid vulvar leiomyoma should also be differentiated from angio-myoflbroblastoma. The key to the differential diagnosis is the presence of interlacing smooth muscle cells and an awareness of tendency toward myxoid change in vulvar leiomyomas.     

Distinction of endometrial stromal sarcomas from 'hemangiopericytomatous' tumors using a panel of immunohistochemical stains.

Endometrial stromal sarcomas are low-grade malignant tumors that may pose a diagnostic challenge, especially when they are present in an extrauterine site. Owing to the presence of an arborizing vasculature and cells with an undifferentiated appearance, endometrial stromal sarcomas can be confused with several soft-tissue neoplasms. We studied 17 endometrial stromal sarcomas, eight hemangiopericytomas, 14 solitary fibrous tumors, and 16 synovial sarcomas immunohistochemically, detecting the following antigens: CD10, estrogen receptor, progesterone receptor, bcl-2, CD34, smooth muscle antigen, epithelial membrane antigen and cytokeratin (AE1/AE3). Most endometrial stromal sarcomas stained positively for CD10 (16/17), estrogen receptor (17/17), progesterone receptor (15/17), and bcl-2 (17/17). Staining with antismooth muscle antigen was seen in 11 of 17 cases of endometrial stromal sarcoma, with more intense staining seen in areas showing smooth muscle differentiation. Staining with AE1/3 was seen in four of 17 endometrial stromal sarcomas, with two of the positive cases containing epithelioid cells. None of the endometrial stromal sarcomas expressed epithelial membrane antigen or CD34. More than half of the hemangiopericytomas (4/8) and solitary fibrous tumors (9/14) cases demonstrated CD10 expression either focally or in a patchy cytoplasmic and membranous pattern. Hemangiopericytomas, solitary fibrous tumors, and synovial sarcomas did not express estrogen receptor. Four of eight hemangiopericytomas and seven of 14 solitary fibrous tumors also showed patchy progesterone receptor expression. CD34 expression was identified in six of eight hemangiopericytomas and 13 of 14 solitary fibrous tumors, but we did not find expression of CD34 in synovial sarcoma. Differences between endometrial stromal sarcoma and other soft-tissue tumors were detected for all of the immunohistochemical markers (P<0.05), except anti-bcl-2 and AE1/3. Antibodies against CD10 mark a substantial number of hemangiopericytomas and solitary fibrous tumors (albeit not diffusely) and should always be combined with antiestrogen receptor and CD34 when the differential diagnosis includes endometrial stromal sarcoma. Unlike estrogen receptor antibodies, progesterone receptor antibodies show at least focal nuclear staining in most hemangiopericytomas, solitary fibrous tumors and rare synovial sarcomas, and are not useful for this differential diagnosis. All endometrial stromal sarcomas expressed bcl-2, mostly in a diffuse pattern, but this did not distinguish between endometrial stromal sarcoma and mimics. We therefore recommend the use of a small antibody panel comprising anti-CD10, anti-estrogen receptor, and anti-CD34 to distinguish endometrial stromal sarcomas from tumors with a predominant hemangiopericytomatous growth pattern.     

Hyaline globules in paucicellular leiomyomas of the gastrointestinal tract are distinct from skeinoid fibers and represent degenerating smooth muscle cells

Skeinoid fibers are globular, brightly eosinophilic periodic Schiff stain (PAS)-positive extracellular collagen deposits commonly seen in gastrointestinal stromal tumors (GIST) of the small bowel. However, smooth-surfaced hyaline globules are occasionally encountered in leiomyomatous GI neoplasms and may be mistaken for true skeinoid fibers. We investigated a total of 93 histologically and immunohistochemically well-characterized true smooth muscle neoplasms of the GI tract for the presence of hyaline globules. A variable number of PAS-positive intracellular and interstitial hyaline globules were detected in all benign paucicellular leiomyomas of the muscularis mucosae (n=72) and the muscularis propria (n=14) irrespective of tumor size and site, but in none of leiomyosarcomas (n=7) and cellular leiomyoma (n=1). In addition, similar findings were rarely seen in the adjacent muscularis propria. Similar to surrounding tumor cells, hyaline globules expressed desmin, α-SMA, and h-caldesmon, but were negative for CD117 and CD34. Ultrastructural examination revealed altered filamentous material in different stages of degeneration with variably condensed matrix and occasional peripheral condensation suggestive of calcification. True skeinoid fibers were not detected. The above findings are consistent with a multistep degenerative phenomenon affecting individual smooth muscle cells in paucicellular GI leiomyomas. Awareness of this finding would prevent misinterpretation as GIST, particularly in small biopsies.     

Gastrointestinal stromal tumors. An immunohistochemical study of cellular differentiation

Forty-five benign and 11 malignant gastrointestinal stromal tumors (GIST) were immunohistochemically studied for the presence of desmin, muscle actins (MA) and S-100 protein. To facilitate the analysis, the tumors were divided into four groups by light microscopy: (1) typical leiomyomas comparable to peripheral leiomyomas (n = 9); (2) cellular spindle cell tumors (n = 29); (3) round cell tumors ("leiomyoblastomas" n = 7); and (4) sarcomas (n = 11). The typical leiomyomas were desmin- and MA-positive throughout, and showed well-differentiated smooth muscle cells by electron microscopy, similar to the normal gastric smooth muscle cells. All esophageal leiomyomas belonged to this group. Nineteen of 29 of the Group 2 tumors showed desmin positivity and 20 of 29 showed MA positivity, but usually only in less than 10% of the tumor cells, and in many instances it was very difficult to determine whether the positive cells were real tumor cells or entrapped muscle cells. Only 5 of 29 of Group 2 tumors showed widespread desmin positivity and 11 of 29 showed similar MA positivity. Of round cell tumors, only 1 of 7 showed desmin-positive cells and 3 of 7 MA-positive cells. None of the sarcomas showed desmin, while MA positivity was found in 6 of 11 cases, often in a large number of tumor cells. Seven tumors showed a significant number of S-100 positive tumor cells, but four of these also showed a high number of desmin- and MA-positive cells, suggesting that these tumors represented complex proliferations of muscle and Schwann cell elements. Two purely S-100 positive benign probably Schwann cell-like tumors were found, both in the small bowel. Small number of S-100 positive cells were commonly found in GIST, and these probably represented entrapped Schwann cells, because many tumors showed simultaneous proliferation of non-neoplastic nerves.     

子宫内膜间质肉瘤9例临床病理分析

目的 探讨子宫内膜间质肉瘤(endometrial stromal sarcoma,ESS)的临床病理特征、诊断、鉴别诊断及预后.方法 对9例ESS患者进行临床、病理资料分析、免疫组化检测及随访.结果 患者年龄39～64岁,中位46.3岁.临床主要表现为阴道流血及子宫增大/占位.肿瘤直径2.3～11 cm,平均4.6 cm.光镜下8例呈低度恶性子宫内膜间质肉瘤(low grade endometrial stromal sarcoma,LGESS),均由类似增殖期子宫内膜间质肿瘤细胞构成,细胞密集,异型性不明显,呈不规则舌状或岛状浸润肌层,并伴较多薄壁螺旋小血管;1例为高度恶性子宫内膜间质肉瘤/未分化子宫内膜肉瘤(high grade endometrial stromal sarcoma/undifferentiated endometrial sarcoma,HGESS/UES),肿瘤细胞直接替代子宫肌层,具有明显的细胞异型性,无LGESS常见的螺旋小血管.免疫组化检测显示肿瘤细胞CD10、vimentin均阳性,PR、ER大部分阳性,SMA和desmin及h-Caldesmon为极少数局灶阳性,S-100、CD34均阴性.术后随访7例(平均53个月),只有1例HGESS/UES死亡.结论 ESS是女性生殖道很少见的一种恶性肿瘤,恶性度相差很大.确诊主要依靠其临床病理特点,并辅以免疫组化标记综合分析.诊断时要与子宫内膜间质结节、平滑肌肿瘤、低分化癌等鉴别.     

Immunohistochemical differentiation of leiomyocellular tumors and tumors with myogenic differentiation

The expression of alpha smooth muscle actin, muscle specific actin, desmin, h-caldesmon, and calponin was studied immunohistochemically in the following soft tissue and bone tumours and tumour-like lesions: muscle fibromatosis, inflammatory pseudotumours, chondroblastoma, enchondroma, chondrosarcoma, fibrous dysplasia, ossifying myositis, osteoblastoma, convential osteosarcoma, leiomyoma and leiomyosarcoma. Tumours and tumour-like lesions with myofibroblastic cells, osteoblasts and chondroblasts frequently exhibited intensive immunoreactivity for the muscle markers, and therefore, some of them may occasionally be confused with leiomyoma and leiomyosarcoma. Calponin does not help to differentiate various mesenchymal tumours expressing muscle markers, because it also stains intensively myofibroblasts, osteoblasts and chondroblasts. We confirmed that h-caldesmon was expressed intensely in leiomyomas and leiomyosarcomas, and never in the other tumours examined, with the exception of three chondroblastomas. The results have shown that h-caldesmon is a rather specific and sensitive marker for smooth muscle tumours, but it can also stain some actin positive myochondroblasts. It is possible that the positivity of h-caldesmon in some chondroblastomas is due to their complete myogenic transdifferentiation, and so we use the term myochondroblasts and myochondrocytes for designation of such S-100 protein, actin, and h-caldesmon positive cells.     

Calponin and h-caldesmon in soft tissue tumors: consistent h-caldesmon immunoreactivity in gastrointestinal stromal tumors indicates traits of smooth muscle differentiation.

Currently, the immunohistochemical evaluation of smooth muscle differentiation is usually based on desmin, which also reacts with skeletal muscle and is not present in all smooth muscle tumors, and alpha-smooth muscle actin, which reacts with myoepithelial cells. Neither marker typically reacts with gastrointestinal stromal tumors (GISTs), previously classified as smooth muscle tumors or presently often classified as smooth muscle/stromal tumors. Two cytoskeleton-associated actin-binding proteins, calponin (CALP) and h-caldesmon (HCD), are putative smooth muscle markers that also react with myoepithelia. These markers are of particular interest in the immunohistochemical analysis of tumors; neither of them has been extensively documented in soft tissue tumors. In this study, we evaluated selected normal and reactive tissues and more than 250 mesenchymal tumors for CALP and HCD. Both markers were expressed in parenchymal and vascular smooth muscle cells in various organs and in myoepithelial cells. CALP also reacted with myofibroblasts of desmoplastic stroma. All of our 25 benign smooth muscle tumors from various locations were positive for CALP and HCD, as were most of the retroperitoneal and uterine leiomyosarcomas. HCD was more specific, because CALP also reacted with myofibroblastic lesions. The common reactivity of malignant fibrous histiocytomas with CALP and HCD suggests a combination of myofibroblastic and smooth muscle differentiation in these tumors. The GISTs (c-kit positive, usually actin negative) showed nearly consistent HCD reactivity, suggesting traits of smooth muscle differentiation. GISTs were usually CALP negative and showed a CALP expression pattern similar to that of alpha-smooth muscle actin. Although nonmuscle, nonmyofibroblastic tumors were negative for CALP and HCD, synovial sarcomas showed streaks of CALP-positive cells of unknown significance. CALP and HCD should be explored as markers to identify myofibroblastic and smooth muscle cell differentiation in mesenchymal tumors.     

Inhibin and CD99 (MIC2) expression in uterine stromal neoplasms with sex-cord-like elements.

Uterine mesenchymal neoplasms with sex-cord-like elements are designated as endometrial stromal tumor with sex-cord-like elements (ESTSCLE) or uterine tumor resembling ovarian sex-cord tumor (UTROSCT), depending on the extent of sex-cord-like differentiation. Occasionally, sex-cord elements similar to those in ESTSCLE and UTROSCT occur in uterine adenosarcomas. To determine whether the sex-cord-like elements in these tumors show immunohistological evidence of sex-cord differentiation, we studied a series of uterine neoplasms for expression of inhibin, a peptide hormone expressed by normal ovarian granulosa cells and ovarian sex-cord neoplasms, and CD99, a protein also expressed by granulosa cells, Sertoli cells, and some ovarian sex-cord tumors. Thirty uterine mesenchymal neoplasms (five epithelioid or plexiform smooth muscle tumors, three endometrial stromal tumors, two mixed endometrial stromal and smooth muscle tumors, 10 ESTSCLE, five UTROSCT, and five miscellaneous stromal processes) and five epithelial neoplasms were evaluated for expression of CD99 (clone 12E7) and inhibin (clone R1) in formalin-fixed, paraffin-embedded tissue. Three of 10 (30%) ESTSCLE and five of five (100%) UTROSCT were inhibin and CD99 immunoreactive. Inhibin staining was confined to the areas with sex-cord-like differentiation, and staining was generally much stronger and more extensive in areas featuring prominent foam cells. There were no differences in the degree or intensity of staining for inhibin in premenopausal and postmenopausal women. CD99 expression tended to correlate with inhibin and was typically confined to similar cell types in the individual neoplasms. Weak CD99 immunoreactivity was seen in one additional epithelioid smooth muscle tumor, whereas all other mesenchymal and epithelial neoplasms studied for inhibin and CD99 were negative. These results provide further immunohistological support for true sex-cord differentiation within uterine mesenchymal proliferations and suggest that the degree of sex-cord differentiation may correlate with the expression of these markers.     

Fibromyxoid variant of endometrial stromal sarcoma with atypical bizarre nuclei

Endometrial stromal sarcoma (ESS) is the second most common malignant uterine mesenchymal tumor. It affects women primarily in the perimenopausal age group. ESSs are morphologically heterogeneous. The distinction between uterine smooth muscle tumors such as cellular leiomyoma and myxoid leiomyosarcoma and low-grade ESS can be problematic when stromal sarcomas show prominent smooth muscle differentiation and abundant myxoid stroma, respectively. We herein present a rare case of fibromyxoid variant of ESS, which was misdiagnosed as hydropic leiomyoma on intraoperative frozen section examination. Grossly, the uterine mass consisted of intracavitary and intramural portions. The intracavitary portion with extensive hydropic degeneration mimicked a hydropic leiomyoma. In contrast, the intramural portion displayed an obvious tongue-like myometrial invasion. Histologically, the tumor consisted of both cellular (20%) and myxoid (80%) areas. In the cellular areas, oval to spindle-shaped tumor cells with bland nuclear features were found to surround concentrically a rich vascular network of arterioles, a characteristic of ESS. In addition, two relatively well-circumscribed nodular lesions showing atypical bizarre nuclei were identified in the myxoid area. Immunohistochemically, the tumor cells were diffusely and strongly positive for CD10. The present case indicates a wide morphological spectrum of ESS. Fibromyxoid variant of ESS should be considered in the differential diagnosis of intracavitary and/or intramural uterine mesenchymal tumors with myxoid differentiation. It is important to avoid confusion between fibromyxoid ESS and myxoid leiomyosarcoma because of the differences in their clinical course, treatment, and prognosis.     

Antibody specific to muscle actins in the diagnosis and classification of soft tissue tumors

A series of soft tissue tumors, melanomas, carcinomas, and lymphomas were studied immunohistochemically for the presence of muscle actins (MA) with the monoclonal antibody HHF-35, and for the presence of desmin for comparison. In nonneoplastic tissues, MA immunoreactivity was present in skeletal and smooth muscle cells, in the pericytes of small vessels, and in the myoepithelial cells. Desmin immunoreactivity had a similar distribution, except that the pericytes of small vessels and myoepithelial cells were negative. All 17 rhabdomyosarcomas were positive for both MA and desmin. Of leiomyosarcomas, 31/32 were positive for MA, and 29/32 for desmin. In pleomorphic undifferentiated sarcomas (malignant fibrous histiocytomas) MA and desmin-positive cells were present in 9/35 and 5/35 cases, respectively. Three of five pleomorphic liposarcomas showed MA-positive tumor cells, which were also desmin-positive in one case. Desmoid tumors often showed a moderate number of both desmin- and MA-positive cells. Hemangiopericytoma, Kaposi's sarcoma, and endometrial stromal sarcoma showed MA-positive staining only in the pericytes and not in the neoplastic cells. In various types of carcinomas, melanomas, and lymphomas, MA- or desmin-positive neoplastic cells were not identified. MA, but not desmin, was present in the desmoplastic stroma in many carcinomas. Both MA and desmin are good markers for muscle differentiation and especially serve to identify rhabdomyosarcomas and leiomyosarcomas. These markers are also present in some sarcomas currently regarded as nonmuscle tumors. This may suggest that some of these tumors have differentiation properties related to true myosarcomas. The absence of muscle actin, a pericytic marker, in hemangiopericytoma does not confirm the concept of pericytic nature of this tumor.     

Myxoid variant of adrenocortical carcinoma: report of a unique case

Myxoid variant of adrenocortical carcinomas (ACC) are rare, there being only 11 cases in the literature to date. Reported herein are the findings of a case, which in contrast to all previously reported myxoid ACC, was devoid of typical non-myxoid areas. The patient was a 61-year-old man in whom a left adrenal mass was detected during investigation of Cushing's syndrome. The adrenal was replaced by malignant cells and expanses of myxoid material. The cells were positive for melan-A, synaptophysin, vimentin and alpha-inhibin. The ultrastructural features of the cells were typical of adrenal cortical differentiation. The differential diagnosis of myxoid ACC includes extraskeletal myxoid chondrosarcoma, chordoma, myxoid adenocarcinoma, myxoma, lipomatous tumors, nerve sheath tumors, smooth muscle tumors, gastrointestinal stromal tumor and other sarcomas. The presence of myxoid material in a retroperitoneal lesion raises a broad differential diagnosis in which myxoid adrenocortical neoplasms should be included. Clinicoradiological correlation may be helpful, but special stains, immunohistochemistry and ultrastructural examination may be necessary to establish the diagnosis.