Epithelioid trophoblastic tumor of the broad ligament: a case report and review of the literature

We report an epithelioid trophoblastic tumor, a recently delineated type of gestational trophoblastic tumor (GTT), discovered in the right broad ligament of a 41-year-old woman. The patient had gestational trophoblastic disease and was treated with methotrexate regimen 15 times 10 years earlier. The yellowish, spongy tumor with tiny hemorrhage spots was located in the right broad ligament, adherent to the right ovary. Microscopically, the tumor was circumscribed, with a pushing border, and the epithelial-differentiated tumor cells grew in cords, nests, and sheets within which were aggregates of hyaline material and necrotic debris. Most tumor cells were mononuclear with distinct cell borders, eosinophilic cytoplasm, and had nuclei with occasional indistinct nucleoli. Scattered multinucleated cells consistent with syncytiotrophoblastic cells were also present. Immunohistochemical staining revealed strong diffuse reactivity for cytokeratins (AE1/AE3, CAM 5.2, CK18), and focal reactivity, mainly in syncytiotrophoblastic cells, for beta-human chorionic gonadotropin, human placental lactogen, and inhibin-alpha. The histologic and immunohistochemical features were characteristic of epithelioid trophoblastic tumor and helped to distinguish the tumor from other trophoblastic tumors and squamous cell carcinoma. Our unusual findings in this case included a high level of serum beta-human chorionic gonadotropin, an unusual tumor location, and a higher Ki-67 proliferative index of 47.2%.     

Detection of residual tumor cells in bladder biopsy specimens: pitfalls in the interpretation of cytokeratin stains

Some patients who have had prior bladder biopsies or transurethral resections undergo a repeat resection within several months for various reasons. The detection of a few residual tumor cells in bladder specimens with prior biopsy site changes can be challenging based on histology alone. Immunohistochemistry for cytokeratins may be used as an adjunct in this situation. We have noted several cases in which keratin stains were performed and positive cells were noted, raising the issue as to whether the cytokeratin positive cells were residual tumor cells or stromal cells. Immunohistochemistry for a panel of antibodies [AE1/AE3, CAM 5.2, high molecular weight cytokeratin, smooth muscle actin (SMA), desmin, and anaplastic lymphoma kinase (ALK)] was performed on 29 cases of bladder biopsies with prior biopsy site changes. Of 29 patients, 25 had a prior history of bladder tumor: 17 had invasive high-grade urothelial carcinoma (T1, 5 cases; T2, 11 cases; T3,1 case); 7 had noninvasive high-grade papillary urothelial carcinoma; 1 had noninvasive low-grade papillary urothelial carcinoma). One of the patients with noninvasive high-grade papillary urothelial carcinoma and one of the patents with invasive high-grade urothelial carcinoma had associated carcinoma in-situ. Four patients had prior benign bladder diagnoses: cystitis cystica et glandularis; polypoid cystitis; follicular cystitis; and neurogenic bladder with benign prostate hyperplasia. Of the 29 cases, 6 (21%) had cells with staining for at least 2 of the cytokeratin markers. Cytokeratin (CK) AE1/ AE3 was positive for cells in 8/29 cases (28%). In 6 of these cases, cells displayed a spindle cell and 2 cases a more epithelioid morphology. CAM 5.2 was positive in cells in 5/29 cases (17%); 3 of the cases had spindle cell and 2 cases epithelioid morphology. High molecular weight cytokeratin was expressed in cells in 2/29 cases (7%) with 1 case having spindle cell and 1 epithelioid morphology. SMA was positive in cells with a spindle cell morphology and negative in the more epitheloid cytokeratin positive cells. Desmin was positive in 3/6 keratin positive spindle cells and negative in keratin positive epithelioid cells. ALK was negative in all the cases. Three cases with spindle cell morphology and positivity for at least 1 of the keratins and SMA stains were interpreted as aberrant keratin expression in myofibroblastic cells based on the staining and the morphology of the spindle cells. Another 3 cases with concurrent staining for at least 1 of the keratins, SMA and desmin were consistent with smooth muscle cells on the basis of their cellular morphology. Another 2 cases had cells, which expressed at least 2 CK markers but did not express SMA, desmin, or ALK and a more epithelioid morphology. These cells were interpreted as residual tumors cells. When interpreting CK stains for the detection of residual tumor cells, one should pay attention to the nature of the cells and not assume all CK staining cells are residual tumor cells.     

Cystic adenomatoid tumor of the mediastinum

A case of adenomatoid tumor presenting as a mass in the anterior mediastinum is described. The patient was a 56-year-old woman with left side chest wall pain who showed a mediastinal mass on chest x-ray and CT scans. Thorough clinical and radiographic examination did not reveal any evidence of tumor elsewhere. At surgery, the tumor was found adjacent to the anterior pericardial reflection. Grossly, the tumor measured 5.5 x 5.5 x 3 cm and showed a homogeneous cut surface with numerous cystic structures that varied from 0.5 to 1.5 cm in greatest diameter. Histologic examination showed numerous cystic spaces lined by flattened or cuboidal epithelial cells. The walls of the cysts showed a proliferation of small canalicular structures lined by round to polygonal epithelioid cells with vacuolated eosinophilic cytoplasm. Immunohistochemical studies showed strong positivity of the epithelioid cells for AE1/AE3 cytokeratin, CK5/CK6, and calretinin. Stains for CK7, CK20, alpha-fetoprotein, CD31, carcinoembryonic antigen, MOC 31, and chromogranin were negative. Electron microscopic examination showed numerous long microvilli on the cell surface and abundant tonofilaments/desmosomal plaques in the tumor cells, characteristic of mesothelial cells. The patient is alive and well and free of recurrence 1 year following surgery. Adenomatoid tumor is a rare neoplasm that should be added in the differential diagnosis of anterior mediastinal masses. Immunohistochemical and ultrastructural studies may be of aid in identifying the characteristic features of mesothelial cells and to avoid mistaking this lesion for more ominous conditions.     

HLA-G immunoreactivity is specific for intermediate trophoblast in gestational trophoblastic disease and can serve as a useful marker in differential diagnosis

HLA-G is a nonclassical MHC class I antigen that has been shown to be a specific marker for normal intermediate trophoblast (IT). In this study HLA-G immunoreactivity assessed with an HLA-G specific antibody (4H84) was detected in all 14 cases of choriocarcinoma, 14 placental site trophoblastic tumors, 13 epithelioid trophoblastic tumors, 16 placental site nodules, and nine exaggerated placental sites. In contrast, HLA-G immunoreactivity was not detected in 34 nontrophoblastic uterine neoplasms. HLA-G immunoreactivity was present in all the IT cells of exaggerated placental sites and placental site trophoblastic tumors and in 70-100% of IT cells in placental site nodules and epithelioid trophoblastic tumors. The pattern of distribution of HLA-G in different subpopulations of IT confirms the relationship of various trophoblastic lesions to different types of IT (exaggerated placental site and placental site trophoblastic tumor to implantation site IT and placental site nodule and epithelioid trophoblastic tumor to chorionic-type IT) and suggests that choriocarcinoma is related to villous-type IT because the majority of mononucleate cells in this neoplasm were HLA-G immunoreactive. In conclusion, HLA-G immunoreactivity appears to be specific for IT in gestational trophoblastic disease and can serve as a useful marker in the differential diagnosis of these lesions.     

The frequency and distribution of intratubular trophoblast in association with germ cell tumors of the testis

Although the presence of intratubular trophoblast (ITT) has been reported, its frequency and distribution in association with germ cell tumors (GCT) have not been investigated. Beta human chorionic gonadotropin (hCG) is a sensitive immunohistochemical marker of syncytiotrophoblast. We therefore wished to investigate whether intratubular trophoblastic elements could be identified adjacent to invasive tumors using immunohistochemistry against hCG. Seventy-five GCTs were examined. Immunochemistry was performed for hCG. Both invasive tumor and seminiferous tubules were examined for positive staining. The seminomas showed ITT in five of 29 cases. All these cases had trophoblastic cells as part of the invasive tumor. Only one of 36 cases of nonseminoma and one of nine of the mixed GCTs (11%) showed ITT. Again, all of the positive cases had hCG-positive trophoblastic cells within the invasive tumor. ITT can be identified adjacent to GCTs in a significant number of cases. We suggest that this is a genuine in situ lesion, associated with seminomas with syncytiotrophoblastic cells. Differentiation toward trophoblastic elements in GCTs may occur at an earlier stage of their pathogenesis than has been previously recognized.     

Solitary cylindroma (dermal analog tumor) of the breast: a previously undescribed neoplasm at this site

The authors report a previously undescribed small, well-demarcated breast tumor similar to a dermal cylindroma in a 63-year-old woman. The tumor was an incidental finding in a lumpectomy specimen for infiltrating lobular carcinoma. The cylindroma was surrounded by normal-appearing breast parenchyma and had the typical "jigsaw" pattern of epithelial basaloid islands. The islands showed focal squamous and myoepithelial differentiation. A notable number of reactive dendritic Langerhans cells permeated the epithelial cell islands, a feature considered to be characteristic of dermal cylindroma. There was also ductal differentiation. Thick bands of hyaline periodic acid-Schiff (PAS) stain and collagen IV-positive basement membrane material bordered the cell islands, and PAS-collagen IV-positive hyaline globules were seen within the cell islands. There was no nuclear pleomorphism or mitotic figures. The cylindroma did not express gross cystic disease fluid protein 15, carcinoembryonic antigen, estrogen and progesterone receptors, or cytokeratin 20 (CK20). There was diffuse and strong immunoreactivity to CK AE1/AE3, and focal reactivity for CK7 and smooth muscle actin. Cylindroma of the breast should be distinguished from adenoid cystic carcinoma and basal cell carcinoma. Although clearly epithelial, the exact histogenesis and cell phenotype of this unusual dermal type cylindroma of the breast are unknown.     

Lymphohistiocytoid variant of malignant mesothelioma of the pleura: a series of 22 cases

The lymphohistiocytoid variant of diffuse malignant mesothelioma is rare with very few cases described in the literature. It is characterized by mesothelial cells with a histiocytelike appearance and an associated dense lymphoid infiltrate. We studied clinicopathologic features and immunohistochemical patterns of a series of 22 cases. The histiocytelike cells had a mesothelial immunophenotype: AE1/AE3 (100%), calretinin (100%), CK5/6 (46%), and EMA (52%). The prominent lymphoid component showed a cytotoxic T-cell immunophenotype. Prognosis was similar to that of a large series of epithelioid diffuse malignant mesotheliomas. Formely, it was classified within the sarcomatoid type. We suggest that it should be reclassified as an epithelioid variant because of its similar behavioural characteristics. There was no evidence of Epstein-Barr virus-related infection.     

Cyclin E and p16 immunoreactivity in epithelioid trophoblastic tumor--an aid in differential diagnosis

Epithelioid trophoblastic tumor (ETT) is a relatively uncommon trophoblastic tumor that can be confused with several trophoblastic and nontrophoblastic lesions, notably the placental site nodule and invasive squamous carcinoma of the cervix. In this report, we analyzed the immunoreactivity of two cell cycle-regulated proteins, cyclin E and p16, in ETTs, placental site nodules and cervical squamous carcinomas to determine whether they are useful in their differential diagnosis. Other trophoblastic lesions were also evaluated. Using an H-score based on both percentage of positively stained cells and immunointensity, we found that ETTs demonstrated a much higher cyclin E staining score than placental site nodules (P<0.0001) permitting distinction of ETTs and placental site nodules with a sensitivity of 94.7% at a specificity of 91.7% using a cutoff H-score value of >40. Only two placental site nodules had scores above the cutoff and both showed morphologic features that placed them in an intermediate position between a typical placental site nodule and an ETT, so-called "atypical PSN." p16 immunoreactivity, was not detected in any of the ETTs and placental site nodules, whereas it was strongly and diffusely positive in the vast majority of cervical squamous carcinomas examined (83/87 cases) (P<0.001). Therefore, cyclin E expression is useful in distinguishing an ETT from a placental site nodule and p16 expression is useful in distinguishing an ETT from a cervical squamous carcinoma. The majority of other types of trophoblastic lesions showed diffuse and intense nuclear immunoreactivity for cyclin E whereas none were positive for p16.     

Myoepithelial Carcinoma: A Rare Neoplasm of the Breast

BACKGROUND: Malignant myoepitheliomas of the breast are extremely rare. There has been a limited number of published reports of myoepithelial carcinomas originating from the breast. CASE REPORT: We describe a malignant myoepithelioma of the breast in a 56-year-old woman. Histological examination showed polygonal epithelioid cells and spindle cells with moderate to marked nuclear atypia. Immunohistochemistry showed reactivity in the spindle cells for smooth muscle actin, cytokeratin (AE1/AE3), and p63, indicating a myoepithelial cell lineage of tumor cells. The patient underwent radical surgical excision of the lesion and axillary lymph node dissection. She demonstrated no evidence of recurrence over an 11-month follow-up. CONCLUSIONS: We suggest myoepithelial carcinomas of the breast be managed with appropriate surgical clearance. A multidisciplinary approach is usually required.     

Perivascular epithelioid cell tumor ('PEComa') of the uterus: a subset of HMB-45-positive epithelioid mesenchymal neoplasms with an uncertain relationship to pure smooth muscle tumors.

The family of lesions thought to be composed at least in part of perivascular epithelioid cells, characterized as HMB-45-positive epithelioid cells with clear to eosinophilic granular cytoplasm and a propensity for a perivascular distribution, includes some forms of angiomyolipoma and lymphangioleiomyomatosis, as well as clear cell "sugar" tumor (CC-SUGAR). When composed predominantly or exclusively of epithelioid cells, it has been suggested that these lesions be classified as "perivascular epithelioid cell tumors" (PEComa). Four cases of uterine PEComa have been described in the literature, three of which exhibited aggressive behavior. We report the clinical, histologic, and immunohistochemical features of eight more examples of uterine PEComa. Patients ranged in age from 40 to 75 years (mean 54 years). Most patients presented because of abnormal uterine bleeding, and grossly a mass was present in the uterine corpus. Morphologically, the tumors could be divided into two groups (A and B). Group A tumors demonstrated a tongue-like growth pattern similar to that seen in low-grade endometrial stromal sarcoma and were composed of cells that tended to have abundant clear to eosinophilic pale granular cytoplasm, diffuse HMB-45 expression, and focal muscle marker expression. Group B tumors were composed of epithelioid cells with less prominent clear cell features, smaller numbers of which were HMB-45-positive. They also featured extensive muscle marker expression and a lesser degree of the endometrial stromal sarcoma growth pattern seen in group A tumors. Two of the four patients with group B tumors had pelvic lymph nodes involved by lymphangioleiomyomatosis, and one of these patients had the tuberous sclerosis complex. Seven of the eight patients with PEComas were treated by hysterectomy. All eight patients are alive and well, although follow-up of >2 years was available only for two patients. Uterine epithelioid smooth muscle tumors and low-grade endometrial stromal sarcomas were compared with the PEComas. Group A PEComas, group B PEComas, and epithelioid smooth muscle tumors were all parts of a continuous histologic spectrum, with group A PEComa at one end of the spectrum and epithelioid smooth muscle tumors at the other, while group B tumors shared features of both. PEComa was histologically and immunohistochemically distinct from endometrial stromal sarcoma. Our data and a review of the literature indicate that PEComa is a subset of HMB-45-positive epithelioid mesenchymal tumors of the uterus with an uncertain relationship to pure smooth muscle tumors. Although none of the patients in this study experienced recurrence during a short follow-up period, some reported in the literature have had recurrences; consequently, we think uterine PEComa should be considered a tumor of uncertain malignant potential until long-term outcome data for a larger number of patients become available.     

Immunoprofile of a carcinosarcoma of the submandibular gland.

Carcinosarcomas are a very rare group of true malignant tumors of the salivary gland. As the name indicates, the tumor is composed of an epithelial and a mesenchymal component, both malignant. We report a case of carcinosarcoma of the submandibular gland in an 86-year-old woman. The epithelial component showed a squamous carcinoma phenotype, whereas the mesenchymal component was morphologically similar to a fibrosarcoma. The epithelial component was strongly positive for CK13, CK14, and AE1/AE, and groups of positive cells were seen for CK19 and vimentin. The whole mesenchymal component was positive for vimentin, negative for cytokeratins, and focal cells were positive for smooth- muscle actin. Both components were strongly positive for P53 and Cyclin D1, and focally positive for MDM2. Rare multinucleated giant cells showed expression of CD68, and focal dendritical cells on carcinomatous nests were positive for S-100. The CK7, CK8, Factor XIIIa, c-erbB-2, P16, CDK-4, Rb1, and E2F-1 were not detected in these 2 groups of malignant cell populations.     

Thymoma arising within cardiac myxoma

Hematopoietic, glandular, and mesenchymal elements can be found within cardiac myxomas; ectopic endocrine tissues and "thymic rests" have also rarely been described. Atrial tumors (one right and one left) from 2 patients (a 69-year-old man and a 77-year-old woman) were encountered among the atrial myxoma cases in one of the author's consultation files. Both tumors were comprised of classic cardiac myxoma (with characteristic rings and syncytial chains of myxoma cells in a loose myxoid matrix) and cellular thymoma-like elements (characterized by a lobulated sheet-like growth of epithelioid spindle cells admixed with small lymphocytes punctuated by vessels with prominent perivascular spaces). Neither patient had evidence of thymoma elsewhere. Immunophenotypically, the thymoma-like component reacted strongly with antibodies to keratins (AE1/AE3, Cam 5.2, wide spectrum, CK19, CK7) and CD57 and weakly with antibodies to CD31, CD34, and calretinin. This intermediate phenotypic expression of both epithelial and vascular antigens likely reflects the multipotential nature of the cells comprising this lesion. The most likely explanation for this extremely unusual finding is neoplastic transformation of thymic rests within a myxoma.     

Clear cell myomelanocytic tumor of the urinary bladder

Clear cell myomelanocytic tumors are a recently described neoplastic growth considered to be a member of the family of perivascular epithelioid cell tumor. These tumors have a predilection for falciform ligament/ligamentum teres. We report an additional case arising from the muscularis propria of the urinary bladder in a 33-year-old woman. The tumor consisted of clear to eosinophilic, epithelioid, and spindled cells arranged in fascicles or packets. A delicate vascular stroma was found among the nests. Immunohistochemically, the tumor cells were typically positive for HMB-45 and smooth muscle actin but negative for S-100 protein, Melan-A, desmin, and pan-cytokeratin. The patient has been free of the disease since the excision of the tumor 6 years ago. This case, in association with the expanding list of perivascular epithelioid cell tumor reported in different sites, suggests that this type of neoplasm may be ubiquitous.     

Clinical efficacy of superselective arterial embolization in the treatment of hemorrhage from malignant gestational trophoblastic tumor

<正>Objective:To evaluate the efficacy of superselective arterial embolization in controlling hemorrhage from malignant gestational trophoblastic tumor. Methods:From February 1990 to January 2008,44 patients with hemorrhage from malignant gestational trophoblastic tumor(including 29 cases of choriocarcinoma and 15 cases of invasive mole) were treated with superselective arterial embolization.The hemorrhage sites included uterus(40 cases),cervical metastasis(1 case) and vaginal metastasis (3 cases). Results:In 41 cases(93.2%),superselective arterial embolization successfully controlled the hemorrhage. Hysterectomy was performed in the 3 failed cases and uterine perforation was revealed by laparotomy.Five patients had normal term delivery after successful superselective arterial embolization and chemotherapy,and two patients are now in the healthy second trimester of pregnancy. Conclusion:Superselective arterial embolization can effectively control the hemorrhage from malignant gestational trophoblastic tumor.     

超选择性动脉栓塞术治疗恶性滋养细胞肿瘤灶大出血的疗效观察

目的评价超选择性动脉栓塞术控制恶性滋养细胞肿瘤灶大出血的效果。方法自1990年2月至2008年1月,因瘤灶造成阴道大出血而行超选择性动脉栓塞术治疗的恶性滋养细胞肿瘤患者44例,其中绒毛膜癌29例、侵蚀性葡萄胎15例;子宫原发灶大出血者40例、宫颈转移灶出血1例、阴道转移瘤破裂出血3例。动脉栓塞治疗后所有患者均接受了化学药物治疗。结果通过超选择性动脉栓塞术控制出血41例,止血有效率为93%(41/44);栓塞止血失败3例。39例(89%)患者化疗后获痊愈,其中5例再次妊娠并足月分娩,2例末次随诊时已正常妊娠。结论超选择性动脉栓塞术可有效控制恶性滋养细胞肿瘤灶的大出血。     

胰腺浆液性小囊性腺瘤临床与病理分析:附四例

目的 分析胰腺浆液性小囊性腺瘤(serous microcystic adenoma,sMA)的临床、病理特点及治疗.方法 回顾性分析4例sMA的临床表现、病理特征及治疗结果 .行PAS染色及CK7、CK20、AE1/AE3、EMA、CA19-9、CEA、34βE12、P63、SMA、Vim、S-100、CgA、Syn、NSE、ER、PR等免疫组织化学检测.结果 病人平均年龄66岁,因体检发现肿块或因其它疾病人院.巨检肿块呈蜂窝状,镜下见大小不等囊腔,囊内衬单层立方或扁平上皮,胞质透亮或嗜酸性.小囊间为胶原纤维分隔.肿瘤无包膜.上皮PAS染色及CK7、EMA、AE1/AE3均全部弥漫阳性.病人均出现手术并发症.结论 胰腺sMA好发于老年人,多为偶然发现.肉眼观呈蜂窝状,镜下小囊内衬一致性富于糖原的上皮,无包膜.免疫组化检测CK7、EMA、AE1/AE3全部阳性.肿块局部彻底切除是最佳治疗方案,但对于无症状的手术耐受力差的病人建议明确诊断后行保守治疗.     

Immunohistochemistry of choriocarcinoma: an aid in differential diagnosis and in elucidating pathogenesis

Choriocarcinoma is traditionally described as being composed of cytotrophoblast and syncytiotrophoblast. Microscopically, these 2 types of cells are intimately associated with each other, forming a characteristic biphasic plexiform pattern, however, the nature of these 2 types of trophoblastic cells is not well understood. In this study, we used immunohistochemistry for several trophoblastic markers to analyze the trophoblastic subpopulations in 36 gestational choriocarcinomas. Eighty-one specimens including placenta, complete mole, placental site nodule, epithelioid trophoblastic tumor, and placental site trophoblastic tumor were analyzed. The antibodies included Mel-CAM, HLA-G, MUC-4, and beta-catenin. A semiquantitative assessment of positive cells and the cellular localization of these markers were recorded. We found diffuse strong membranous and cytoplasmic staining for MUC-4 in mononucleate cells in all 36 cases (100%) and a similar pattern of localization in 28 cases (78%) for HLA-G. This distribution was similar to that in normal placentas, where MUC-4 and HLA-G are expressed in the trophoblastic cells of the trophoblastic columns and implantation site. In choriocarcinoma, mononucleate trophoblastic cells showed moderate immunoreactivity for Mel-CAM, a specific marker for implantation site intermediate trophoblast, in 78% of the cases. The MUC-4, HLA-G, and Mel-CAM-positive trophoblastic cells were larger than cytotrophoblastic cells, with more abundant cytoplasm, consistent with the morphology of intermediate trophoblast. In contrast, 31% of the choriocarcinomas contained a very small proportion (<5%) of mononucleate trophoblastic cells compatible with cytotrophoblast that was positive for nuclear beta-catenin, a cytotrophoblast-associated marker. These results suggest that choriocarcinoma is composed predominantly of a mixture of syncytiotrophoblast and intermediate trophoblast with only a small proportion of cytotrophoblast. The presence of nuclear beta-catenin staining in the cytotrophoblast of choriocarcinoma is consistent with the view that choriocarcinoma develops from transformed cytotrophoblastic cells which are presumably the cancer stem cells that differentiate into either intermediate trophoblast or syncytiotrophoblast.