Ovarian serous borderline tumors with stromal microinvasion: a report of 21 cases

The clinicopathologic features of 21 cases of otherwise typical serous borderline tumors that contained small foci of stromal invasion were reviewed. The mean age of the patients was 43 years and six of them were pregnant at the time of diagnosis. Nineteen tumors were stage I, one was stage III (para-aortic lymph node involvement) and one was stage IV (parenchymal liver metastasis). The tumor invaded the stroma predominantly as individual cells or nests or clusters of cells with abundant eosinophilic cytoplasm (17 cases), as small confluent nests with a cribriform pattern (two cases) and as rounded aggregates of papillae (two cases). Seven women were treated with bilateral salpingo-oophorectomy and hysterectomy; 13 had less than bilateral oophorectomy. Of the 17 patients for whom followup data were available, 16 were without evidence of disease 1 to 11 (mean, 5.2) years postoperatively, and one patient had a serous borderline tumor with microinvasion in a conserved contralateral ovary 2.8 years postoperatively, but was well 6 months after a partial oophorectomy. These data suggest that serous borderline tumors with microinvasion have a prognosis similar to that of the usual serous borderline tumor, and that conservation of the contralateral ovary and uterus may be acceptable therapy in young women who wish to preserve their fertility.     

Borderline malignant serous tumors of the ovary maintained on extracellular matrix: evidence for clonal evolution and invasive potential

Four cases of advanced stage (II or III) and one case of early stage (IC) borderline malignant serous cystadenocarcinomas of the ovary were maintained on culture dishes coated with an extracellular matrix (ECM) produced by bovine corneal endothelial cells. Cells harvested for chromosomal analysis after 2-3 days showed diploid or near-diploid modalities in all cases. Banded chromosome studies in two cases revealed nonrandom clonal abnormalities with trisomy 2, 7, and 12 in seven of 13 metaphases. No structural abnormalities were noted. These cytogenetic findings differ from those found in malignant serous tumors of the ovary. In addition, borderline tumor cells digested the ECM in all cases and formed a cribiform pattern within a few days of primary culture. This study suggests clonal progression from early to advanced stages of borderline malignant serous tumors; readily distinguishable from overtly malignant serous tumors of the ovary. Ability of tumor cells derived from both primary tumors and metastatic implants to digest the ECM implies the possibility that borderline serous tumors have invasive potential.     

Ovarian involvement by the intra-abdominal desmoplastic small round cell tumor with divergent differentiation: a report of three cases.

Three girls, one 14 and two 15 years of age, with the recently described neoplasm that has been designated "intra-abdominal desmoplastic small round cell tumor with divergent differentiation," and ovarian involvement at presentation are described. In two cases the ovarian tumor was initially thought to be the primary neoplasm. In all cases there was extensive extraovarian tumor at the time of presentation. The ovarian involvement was bilateral in two cases and unilateral in the third. Microscopic examination showed prominent nodular growth within the ovaries. The tumors were characterized predominantly by nests of small cells with hyperchromatic nuclei and scant cytoplasm separated by a prominent desmoplastic stroma. A few tubules containing mucinous secretion were present in one case. On immunohistochemical staining many of the tumor cells stained positively for cytokeratin, epithelial membrane antigen, desmin, and vimentin. Staining for neuron-specific enolase was present in two cases but was conspicuous in only one of them. Leu-7 was expressed by the tumor cells in two cases, and S-100 protein by one, giving further support to the possibility of neuroectodermal differentiation within some of these neoplasms. The two cases studied by electron microscopy both showed frequent intercellular junctions, basal lamina, cytoplasmic filaments, and sparse, small dense granules of either neuroendocrine or lysosomal type. Paranuclear aggregates of filaments were found in one case and cellular processes were prominent in the other case. The differential diagnosis in these cases was extensive and included a number of small cell tumors that may involve the ovary, either primarily or secondarily, in young females. The desmoplastic small round cell tumor should be considered in such cases when the appearances on routine examination are consistent with the diagnosis, and appropriate immunohistochemical stains should be performed to confirm the diagnosis.     

子宫和卵巢腺瘤样瘤的临床病理分析

目的 探讨女性生殖系统腺瘤样瘤的发生、免疫组织化学表达的特征及鉴别诊断。方法 对24例子宫和卵巢腺瘤样瘤进行临床病理及免疫组织化学观察。结果 24例患者中腺瘤样瘤发生于子宫者21例,卵巢者2例,子宫与卵巢同时发生者1例,分别占本院同期子宫及卵巢肿瘤及瘤样病变的0.34%和0.06%。免疫组织化学染色显示：波形蛋白及细胞蛋白（AE1／AE3）均为阳性,呈双相表达;第八因子相关抗原（FⅧRAg)均为阴性;S－100蛋白20例阳性（83.3%),上皮膜抗原（EMA）4例阳性（16.7%);其中10例行calretinin蛋白染色,均为阳性表达。结论 女性生殖系统腺瘤样瘤为间皮起源,子宫为最常见部位。免疫组织化学染色结果可作为诊断及鉴别诊断的重要参考依据。其生物学行为为良性,预后良好。     

Extrauterine low-grade endometrial stromal sarcoma: Report of three cases

Three cases of rare low-grade endometrial stromal sarcoma of the extrauterine tissue are presented. Each one occurred In the ovary, pelvic and abdominal cavities. Two were associated with endometriosls. Histologically, the tumors were characterized by an infiltrative and diffuse proliferation of uniform round or oval cells, abundant small vessels, low mitotic activity, the presence of foam cells and vascular Invasion. lmmunohistochemically, all tumors expressed vimentin, muscle markers (desmin, muscle-specific actin and α-smooth muscle actin) and progesterone receptors. Two tumors were diploid and one was aneuploid by flow cytometry. All patients were well with no evidence of disease 16–39 months after surgery. It Is suggested that this neoplasm may arise with or without endometriosis under hormonal Influence. This rare variant of Müllerian tumors should not be confused with adenosarcoma and soft tissue tumors, such as smooth muscle tumors and solitary fibrous tumor.     

33例粘膜相关淋巴组织起源的恶性淋巴瘤临床病理观察

33例粘膜相关淋巴组织(MALT)起源的恶性淋巴瘤,具有MALT的特点,发展缓慢,局限生长,主要由滤泡中心细胞和B_2样细胞构成,可见浆化和毛细血管后微静脉壁淋巴细胞浸润。特征改变是“淋巴上皮病变”。当侵犯性生长时,可出现绣毯结构。病变早期,B_2样细胞为主时,局部治疗有效,病人预后较好。     

Aspiration biopsy cytology of papillary carcinoma of the breast.

The fine-needle aspirates of two cases of noninfiltrating papillary carcinoma (PC) and three examples of early invasive PC of the breast were examined. In three cases in which the tumors displayed cuboidal or polygonal cells the aspirates showed papilla-like clusters of tumor cells with relatively "strong" cellular cohesiveness. Single and small aggregates of tumor cells as well as hemosiderin-laden or foamy macrophages were also present. Aspirates from the two PCs predominantly consisting of tall columnar epithelial cells revealed only monolayered and multilayered epithelial fragments with folding in one case. In the other case large epithelial fragments and small tight clusters of polygonal tumor cells were present. No bipolar nuclei of myoepithelial cells were identified in all cases. No specific cellular features permitting the differentiation between noninfiltrating and early invasive breast PCs were identified in this small series. Staining for carcinoembryonic antigen using the peroxidase-antiperoxidase technique was performed on aspiration smears of three cases. It revealed a positive cytoplasmic reaction in two cases.     

Frequency of alpha-fetoprotein production by Sertoli-Leydig cell tumors of the ovary: an immunohistochemical study of eight cases

Eight Sertoli-Leydig cell tumors (SLCT) of the ovary were studied by immunostaining for alpha-fetoprotein (AFP). Immunostaining was positive only in cells resembling Leydig cells in three cases and in both Sertoli and Leydig cells in one instance. In one SLCT with positive immunostaining, serum AFP was available and was elevated. Serum level was not measured in the seven other cases. Despite the small number of cases, this study suggests that AFP expression in ovarian SLCT is not unusual. The serum AFP level may, however, depend on the size of the tumor, the proportion of Leydig cells present, and their ability to produce and to release AFP into the bloodstream.     

Ovarian neoplasms composed of small round cells: a review

Ovarian neoplasms composed predominantly or exclusively of small round cells with scant cytoplasm are relatively rare. However, there is a wide differential, and pathologists often struggle to make a correct diagnosis because of overlapping histologic features. Perhaps the best known of these neoplasms is ovarian small cell carcinoma of hypercalcemic type (OSCCHT), a tumor of unknown histogenesis. This may be confused with a wide range of neoplasms ranging from sex cord-stromal tumors (some of which may exhibit a small cell phenotype) to neoplasms in the family of small round blue cell tumors to various undifferentiated malignancies. A neuroendocrine small cell carcinoma, so-called small cell carcinoma of pulmonary type, may also arise within the ovary, and this may be a component of a typical ovarian surface epithelial-stromal tumor. In addition to the well-known family of small round blue cell tumors of childhood, other small cell neoplasms that may arise within the ovary or involve the ovary include intra-abdominal desmoplastic small round cell tumor, metastatic small cell carcinoma, peripheral and central primitive neuroectodermal tumor, and endometrial stromal sarcoma. Malignant melanoma, undifferentiated carcinoma, and various germ cell tumors, especially dysgerminoma and immature teratoma, also on occasion enter into the differential diagnosis of an ovarian small cell neoplasm. In this review, the morphologic features of some of these neoplasms are described, as is the value of immunohistochemistry and other ancillary techniques in establishing a diagnosis.     

Sex cord-stromal tumors of the ovary

The developmental relationship between granulosa and stromal cells in the fetal ovary was reviewed. The proliferation and expression of basic fibroblast growth factor (bFGF) and luteinizing hormone receptor (LHR) of both the granulosa and theca cells was examined in the adult ovary. Ovarian granulosa cell tumors were then studied under light and electron microscopy and for immunohistochemical expression of bFGF and LHR. In the follicular development of the adult ovary, bFGF expression in the granulosa cells was correlated with theca cell proliferation. In ovarian granulosa cell tumors, estrogen-producing tumors showed a stratified or microfollicular pattern being accompanied by theca cells which had ultrastructural features of steroid-production, and these tumor cells exhibited immunoreactivity for bFGF. In contrast, tumors with no apparent hormone-production showed a solid or gyriform pattern without admixture of theca cells, and were negative for bFGF. LHR was expressed in both types of tumor. Accordingly, bFGF may play an important role in association with the theca cell component in granulosa cell tumors.     

Secondary tumors of the pancreas: an analysis of a surgical and autopsy database and review of the literature

The vast majority of pancreatic carcinomas are primary, and, among these, more than 90% are of ductal origin. However, a variety of extrapancreatic tumors may involve the pancreas secondarily and may manifest different clinicopathological characteristics and outcomes. In this study, pathology material from 973 surgical specimens and 4955 adult autopsy cases was reviewed to identify the tumors metastatic to or secondarily involving the pancreas. Biliary and periampullary neoplasms and tumors confined to peripancreatic soft tissue were excluded. In the autopsy series, the pancreas was involved by tumor in 190 cases, and 81 of these were secondary tumors. These were predominantly of epithelial origin, most commonly from lung (34), followed by GI tract (20), kidney (4), breast (3), liver (2), ovary (1), and urinary bladder (1). In addition, there were six tumors of hematopoietic origin, two melanomas, two sarcomas, and two mesotheliomas. Among the 973 surgical specimens, 38 cases contained metastatic tumors to the pancreas. Of these, 11 were lymphomas, and the others were carcinomas of stomach (7), kidney (6), lung (2), liver, prostate, ovary, uterus (1 case of each), and a Merkel cell carcinoma. In addition, there were three malignant gastrointestinal stromal tumors and one retroperitoneal leiomyosarcoma. In conclusion, lung cancer is the most common source of metastasis to pancreas, followed by gastrointestinal carcinomas and lymphomas. These tumors are usually seen in patients with disseminated disease and are detected mainly in autopsies. Secondary tumors constitute about 4% of pancreatic specimens in the authors surgical database. Approximately one-third of them are clinically mistaken as primary tumors of the pancreas. These are predominantly hematopoietic malignancies or carcinomas of renal or gastric origin. Secondary tumors should be entertained in both the clinical and pathological differential diagnosis of pancreatic neoplasia.     

Clear cell lymphoma: a clinicopathological study of four cases

Four cases of clear cell lymphoma were studied by means of light and electron microscopy, enzyme-histochemistry, and E- and EAC-rosette formation. On light microscopic examination the tumors were seen to be composed mainly of round, oval, or slight irregular cells with water-clear, abundant cytoplasm. The neoplastic cells has round, oval, or convoluted nuclei with fine, evenly dispersed chromatin and one or more small but distinct nucleoli. On electron microscopic examination the clear cell lymphoma were characterized by lymphoid cells with striking electron lucent cytoplasm with few organelles. According to E-rosette test and enzyme-histochemical findings, the investigators proposed that the clear cell lymphoma may be derived from T-cell lineages. Differentiated diagnoses of clear cell lymphoma from B-immunoblastic sarcoma, pleomorphic cell lymphoma, clear cell sarcoma, and clear carcinomas derived from lung, ovary, or kidney were discussed.     

Miscellaneous rare paratesticular tumors

A few uncommon but distinctive tumors may preferentially involve the paratestis. The 3 unusual tumors that represent the focus of this discussion are the ovarian-type epithelial tumors (OTET), the desmoplastic small round cell tumor (DSRCT), and the melanotic neuroectodermal tumor of infancy (MNTI). The OTETs are testicular homologues of their more common namesake counterparts that arise in the ovary. Most frequent of these are serous tumors of borderline malignancy, with fewer cases of serous carcinomas or other forms of mullerian differentiation. DSRCT is an increasingly recognized, aggressive, "small blue cell" neoplasm with distinctive clinical and pathologic features. These polyphenotypic tumors characteristically, but not invariably, arise in intimate association with the serosal membrane of the peritoneal cavity and harbor a signature translocation-t(11;22)(p13,q12). In the paratestis they often involve the surface of the epididymis. The MNTI is an enigmatic, histologically distinctive, low-grade neoplasm occasionally encountered in the epididymis. Recognition of its features is essential to avoid misdiagnosis as a more aggressive "small blue cell" neoplasm and consequent therapeutic mismanagement. Primary hematopoietic tumors of the paratesticular structures are rare. There appears to be a tendency for young men to have low-grade lymphomas with an indolent course and older patients to develop higher-grade tumors. Plasmacytoma and granulocytic sarcoma of the paratestis are even more rare and are often susceptible to misinterpretation. Finally, metastatic tumors and a variety of other very rare neoplasms are discussed.     

Multicentric infarcted leiomyoadenomatoid tumor: a case report

Adenomatoid tumor is a benign, usually small lesion that may be found within the wall of fallopian tubes or beneath the uterine serosa near the uterine cornu. It is often accompanied by smooth muscle hypertrophy that may obscure the adenomatoid tumor. We herein report a very unusual case of infarcted leiomyoadenomatoid tumor of the uterus and ovary in a 24-year-old woman who presented with severe lower abdominal pain and masses in the uterus and right ovary. Pelvic ultrasonography and computed tomography revealed a 5 cm mass in the myometrium and a 4 cm mass in the right ovary. Laparoscopy-assisted transvaginal mass removal was performed under the clinical impression of a uterine leiomyoma and benign ovarian teratoma. On a microscopic examination, prominent fascicles of smooth muscle separated or infiltrated by cuboidal or signet ring-like vacuolated cells, as well as tubular formations lined by flattened mesothelial cells and extensive necrosis were observed in both masses. The microscopic appearance often suggested the possibility of a malignant neoplasm due to irregular pseudoinfiltration with atypical cuboidal cells and the paucity of a typical adenomatoid tumor due to infarction, and the presence of epithelial-appearing cells in the hypertrophic smooth muscle bundles that mimicked an infiltrating carcinoma for a leiomyoma or myometrium. These unemphasized features of leiomyoadenomatoid tumors may potentially lead to more aggressive therapy than warranted if not correctly interpreted, especially for infarcted cases.     

Recurrence of adult granulosa cell tumor of the ovary: experience at a tertiary care center

Adult granulosa cell tumor (AGCT) is the most common ovarian sex cord stromal tumor with a favorable prognosis. However, a subset of patients develop recurrence. We retrieved and reviewed 156 cases of AGCT reported between 1992 and 2012. The ages ranged from 20 to 84 years (mean, 48 years). The size of the tumor ranged from 0.8 to 25 cm (mean, 10 cm). Histologically, all tumors were composed of round or polygonal cells with indented or grooved nuclei, eosinophilic cytoplasm, and well defined cell borders. A diffuse pattern was seen in the majority followed by microfollicular, trabecular and macrofollicular. The mitotic figures ranged from 2 to a maximum of 21/10 HPFs. Focal necrosis were seen in 17 cases. Associated simple hyperplasia of endometrium was seen in 9 cases, complex hyperplasia in 2, and endometrioid adenocarcinoma of the endometrium in 3 cases. Recurrence was seen in 8 cases with a follow-up of 2 to 19 years (mean, 6 years). The recurrent tumors were mostly >5 cm and sites included the same adnexal site and contralateral ovary, omentum, mesentery of small bowel, abdominal wall, uterine and fallopian tube serosa, lymph nodes, pelvis, and appendix. Histologically, recurrent tumors exhibited a diffuse histologic pattern and a mitotic count of 6.8 as compared to 3.3 in primary tumors. In conclusion, a tumor size of >5 cm and a diffuse histologic pattern were associated with increased recurrence risk. The recurrent tumors hadz increased mitotic figures compared with primary tumors. Appendix, a very rare site of recurrence was seen in one of our cases.     

Small-cell variant of renal oncocytoma

Renal oncocytoma is a distinct benign tumor accounting for approximately 3-5% of all renal tumors. This neoplasm is easily recognizable in its classic form: there are polygonal cells with abundant granular eosinophilic cytoplasm filled with mitochondria. The tumor cells are arranged in nests and tubular pattern. Here, 1 case of renal oncocytoma with a domination of small cells is reported (the so-called "oncoblasts") arising in elderly woman. These small cells have scant cytoplasm, dense hyperchromatic nuclei, and a high nuclear/cytoplasmic ratio. The term "small-cell variant of renal oncocytoma" was proposed for these cases. The unusual extensive small-cell component of the tumor may represent a potential diagnostic pitfall for primary or metastatic malignant small cell tumors.     

New antigens induced by herpes simplex virus in human tumors

Tissues of malignant tumors of the genitalia (cervix, uterus body, ovary) contain a specific antigen associated with herpes simplex virus type 2 (HSV-2) identical with the antigen of the infected cells. The virus-induced antigen was detected in tissues of cervical carcinoma in 35% of cases, in 15% of tumors of the corpus uteri and in 13% of ovary tumors. HSV-2 was isolated from pathologically altered cervical carcinoma cells in 2 out of 56 cases examined. These facts indicate the presence of HSV-2 genetic information in cells of some tumors. No virus-induced antigen was found in any of the 7 specimens of normal nontumorous tissue examined.     

Consistent numerical chromosome aberrations in thecofibromas of the ovary

Sex cord-stromal tumors of the ovary comprise 8% of all ovarian neoplasms. Because they consist of cells that resemble embryonic sex cord and/or specialized ovarian stroma cells, their cytologic and histologic features can be viewed as reflecting a continuum from fibromas to thecomas with thecofibromas in between. Existing cytogenetic knowledge about ovarian thecomas-thecofibromas-fibromas is restricted to 44 cases with chromosomal abnormalities. The most common aberration has been trisomy 12, identified either by karyotyping or using fluorescence in situ hybridization (FISH). We wanted to obtain more information about the genomic composition of these tumors, and, therefore, examined 29 new thecoma-thecofibroma-fibroma tumors of the ovary using karyotyping, comparative genomic hybridization, interphase FISH, and DNA ploidy analysis. We detected aneuploidy in 21 tumors. Trisomy and/or tetrasomy 12 was the most common chromosomal aberration, found in 15 tumors (71.5% of the aneuploid tumors or 51.5% of all analyzed tumors), followed by trisomy for chromosomes 10, 18, 4, and 9. Some monosomies (for chromosomes 4, 9, 10, and 18) were also identified, either as the sole change or in combination with trisomies. The nonrandom occurrence of these aneuploidies in these benign tumors strongly indicates that they play a major pathogenetic role, but how trisomies and other aneuploidies contribute to tumorigenesis remains unknown.     

Metastatic and independent cancers of the endometrium and ovary: a clinicopathologic study of 34 cases

Twenty-one of 34 simultaneous cancers involving the endometrium and ovary were classified as endometrial primary tumors with ovarian metastases. The criteria for this classification were either a multinodular ovarian pattern (major criterion) or two or more of the following minor criteria: small (less than 5 cm) ovary(ies), bilateral ovarian involvement, deep myometrial invasion, vascular invasion, and tubal lumen involvement. Twelve cancers were classified as independent neoplasms, primarily by the absence of the above criteria. Although they were classified as independent, the histologic features of the endometrial and ovarian tumors were the same in 11 of these 12 cases. Only one case represented an ovarian primary tumor with an endometrial metastasis. Both the group believed to have endometrial primaries with ovarian metastases and that with independent primaries showed high incidences of associated endometrial hyperplasia, supporting the belief that the endometrium is a primary site in both groups. The cancers classified as metastatic, with no known spread outside the endometrium-myometrium and ovary, were found to involve other sites significantly (P less than 0.01) more frequently than those classified as independent. Grade 3 endometrioid carcinoma, adenosquamous carcinoma, and malignant mixed müllerian tumors occurred only in the metastatic group, whereas the independent group had a variety of endometrioid and nonendometrioid tumors.     

Sertoliform endometrioid carcinomas of the ovary: a clinicopathologic and immunohistochemical study of 13 cases.

Ovarian endometrioid carcinomas with sertoliform features (SECs) are infrequent and often misinterpreted as sex cord-stromal tumors. The clinicopathologic features and immunohistochemical expression of keratin, epithelial membrane antigen (EMA), inhibin, and estrogen and progesterone receptors were evaluated in 13 cases of SEC. The women were 41 to 89 years of age (mean, 60 yr) with abdominal enlargement secondary to a unilateral ovarian mass as the most frequent clinical presentation. One patient displayed virilization. At presentation, 10 patients were Stage I, one was Stage II and two were Stage III. The tumors were composed of compact anastomosing cords and small tubules embedded within a fibrous stroma. Nuclear features were Grade 1 or 2 in all but one tumor. Areas of conventional endometrioid carcinoma were observed in 12 cases. An adenofibromatous component comprising 5 to 60% of the lesion was present in seven cases. All 12 cases examined immunohistochemically were positive for keratin and EMA and negative for inhibin with focal, luteinized stromal cells positive for inhibin in 10 cases. Estrogen and progesterone receptors were positive in 10 and 11 cases, respectively. Follow-up on 6 of 10 patients with Stage I and the one patient with Stage II disease displayed no evidence of disease 10 to 120 months (mean, 57 mo). Progressive disease and death occurred at 12 and 72 months only in the two women with Stage III disease, one of which had an associated serous carcinoma in the contralateral ovary. Adequate sampling, a careful search for areas of conventional endometrioid carcinoma, and immunohistochemical studies (including EMA, keratin, and inhibin) are helpful in the evaluation of ovarian tumors with sex cord-stromal features. SEC should be considered a well-differentiated endometrioid carcinoma despite the presence of a solid, sex cord-like proliferation, with a good prognosis when confined to the ovary.