Sex Cord-like Differentiation Research Articles

Uterine Tumor Resembling Ovarian Sex Cord Tumor With Aggressive Histologic Features Harboring a GREB1-NCOA2 Fusion: Case Report With a Brief Review.

Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare mesenchymal neoplasm, of uncertain lineage, that shows predominantly sex cord-like differentiation with a broad range of histologic appearances and polyphenotypic immunohistochemical features. Although generally having a favorable prognosis, a subset can recur/metastasize. Most recently, several studies of UTROSCT have described novel fusion genes involving ESR1 and GREB1 as the 5 partner, and NCOA1-3 as the 3 partner. Genotype and phenotype correlation has suggested that GREB1 -rearranged tumors may have a higher tendency to behave aggressively. Herein, we report a UTROSCT with aggressive histologic features harboring a GREB1-NCOA2 fusion. A 51-yr-old woman presented with menometrorrhagia and progressive dysmenorrhea and was found to have a submucous uterine lesion by ultrasonography. Gross examination of the hysterectomy specimen showed an 8.5-cm, polypoid, soft, intracavitary mass. Histologic examination revealed a deeply invasive neoplasm composed of uniform round to plump spindle cells, arranged predominantly in diffuse sheets and fascicles and focally in anastomosing cords patterns. Groups of rhabdoid tumor cells were occasionally noted. Worrisome features, including increased mitotic figures (up to 3/10 high power fields), geographic necrosis, and lymphovascular invasion, were evident. Immunohistochemical analysis showed variable positivity for epithelial, smooth muscle, neuroendocrine, and sex cord markers, as well as hormone receptors. RNA sequencing revealed an in-frame fusion between exon 3 of GREB1 and exon 14 of NCOA2 . Fluorescence in situ hybridization analyses confirmed rearrangements of both the GREB1 and NCOA2 loci. Our case lends further supports that GREB1 -rearranged UTROSCTs frequently exhibit aggressive histological features with inconspicuous sex cord-like differentiation.

Low-grade Endometrial Stromal Sarcoma With Sex Cord-like Differentiation and PHF1-JAZF1 Fusion With Deletions: A Diagnostic Pitfall of JAZF1 FISH.

The molecular knowledge of endometrial stromal neoplasms has been rapidly increasing and is considered complementary to morphologic and immunohistochemical findings for better categorization of these tumors. The most common molecular alteration observed in low-grade endometrial stromal sarcomas is the JAZF1-SUZ12 fusion, whereas, low-grade endometrial stromal sarcoma with sex cord-like differentiation have been shown more commonly to have fusions involving PHF1. Herein, we present a low-grade endometrial stromal sarcoma with sex cord-like differentiation with a fluorescence in situ hybridization showing the apparent loss of one copy of JAZF1 5' and 3' signals, rather than the expected "break-apart" pattern seen in the setting of a JAZF1 fusion. The case was then further evaluated by chromosome microarray and RNA fusion analysis. Overall, the molecular findings supported a PHF1-JAZF1 fusion with deletions right before and after the JAZF1 locus, impairing probe binding and resulting in the unusual "deletion" pattern observed in the JAZF1 fluorescence in situ hybridization, which would not intuitively suggest a fusion involving JAZF1. This case illustrates the importance of integration of morphological and molecular findings as well as the limitations of fluorescence in situ hybridization in detecting fusions, particularly in the setting of more complex chromosomal alterations even though the fusion partners are well-known.

BCOR Expression in Mullerian Adenosarcoma: A Potential Diagnostic Pitfall.

Adenosarcoma can mimic high-grade endometrial stromal sarcoma with ZC3H7B-BCOR fusion that may show entrapped glands and often exhibits diffuse BCOR expression. We encountered diffuse BCOR expression in rare adenosarcomas and sought to define its frequency among a larger cohort of these tumors. BCOR immunohistochemistry was performed on archival formalin-fixed paraffin-embedded tumor tissue in 13 of 14 adenosarcomas with and without stromal overgrowth arising in the uterus or ovary. The staining intensity and percentage of positive tumor nuclei in the mesenchymal component were evaluated. Eleven cases with sufficient tumoral tissue were subjected to fluorescence in situ hybridization for the detection of BCOR, BCORL1, NUTM1, ZC3H7B, and JAZF1 rearrangement. Three cases were subjected to targeted RNA sequencing. BCOR was expressed in 9 of 13 (70%) tumors, including 6 with and 3 without stromal overgrowth. Moderate to strong staining in >70% of cells was seen throughout in 1 low-grade and 6 high-grade tumors, 5 of which had stromal overgrowth. No staining was seen in 3 low-grade and 1 high-grade tumors with stromal overgrowth. One tumor demonstrating extensive sex cord-like differentiation and diffuse BCOR expression harbored JAZF1 and BCORL1 rearrangements. No BCOR or BCORL1 rearrangement was identified in the remaining tumors. BCOR expression is seen in most adenosarcomas with and without stromal overgrowth. BCORL1 rearrangement is seen in rare tumors with diffuse BCOR expression. Assessment of BCOR or BCORL1 rearrangement status is required in adenosarcomas demonstrating BCOR expression.

Values of JAZF1 gene rearrangement detected by fluorescence in-situ hybridization in diagnosis of endometrial stromal tumours

Objective: To investigate the role of JAZF1 gene rearrangement in the diagnosis and differential diagnosis of endometrial stromal sarcomas by fluorescence in situ hybridization (FISH). Methods: JAZF1 gene rearrangement was analyzed by FISH in 129 cases of ESS diagnosed from January 2008 to December 2016 including 105 cases of low-grade endometrial stromal sarcoma (LG-ESS), 21 cases of high-grade endometrial stromal sarcoma (HG-ESS) and 3 cases of undifferentiated uterine sarcoma (UUS). Sixteen cases of the related tumours in uterus were also collected as control group. The results were compared with our previous studies of JAZF1/JJAZ1 fusion gene in ESS by RT-PCR. Results: Detection of JAZF1 gene rearrangement by FISH was successfully analyzed in 144 cases. JAZF1 gene alteration was detected in 63 cases, all of which were LG-ESS, with an overall positivity of 60.6% (63/104), while no JAZF1 gene rearrangement was found in all other cases. JAZF1 gene rearrangement was present in LG-ESS with classic histology (69.3%, 52/75), smooth muscle differentiation (2/10), sex cord-like differentiation (4/5), fibromyxoid change (1/5), clear cell change (0/1), skeletal muscle differentiation (0/1), and schwannoma-like palisading pattern (0/1). The different components in all the cases of LG-ESS with variant histology had the clonal origin, with or without JAZF1 gene alteration. Compared to the results of JAZF1/JJAZ1 fusion gene by RT-PCR, the positive rate of JAZF1 gene rearrangement in LG-ESS by FISH (61.9%, 26/42) was significantly higher than that of RT-PCR (30.0%, 12/40; P<0.01). Conclusions: JAZF1 gene rearrangement is present only in LG-ESS, but not in HG-ESS, UUS or other related tumours in uterus. The frequency of JAZF1 gene rearrangement varies between classic LG-ESS and different morphologic variants. It is frequently, but not consistently, present in classic LG-ESS and less often positive in variant cases. The results of JAZF1 gene alterations in LG-ESS with different morphologic variants support the contention that the endometrial stromal and their variant morphologic components have the same clonal origin. Detection of JAZF1 gene rearrangement by FISH is very useful for the diagnosis and differential diagnosis of ESS.

SF1 immunohistochemistry is useful in differentiating uterine tumours resembling sex cord-stromal tumours from potential histological mimics

The aim of this study was to perform an immunohistochemical comparison of uterine tumour resembling ovarian sex cord-stromal tumour (UTROSCT) and other uterine lesions with sex cord-like (SCL) differentiation. Six UTROSCTs and 10 potential histological mimics with focal SCL elements were examined, the latter comprising three endometrial stromal nodules, three low-grade endometrial stromal sarcomas, three Müllerian adenosarcomas, and one case of adenomyosis. All cases were stained immunohistochemically for SF1, FOXL2, calretinin and inhibin, and for the less specific markers smooth muscle actin, desmin, CD10, CD56, CD99, cytokeratin, oestrogen receptor and progesterone receptor. Three, four, six and three UTROSCT expressed SF1, FOXL2, calretinin and inhibin, respectively. However, calretinin staining was focal (≤50% cells positive) in five of the cases. Three potential histological mimics demonstrated calretinin, FOXL2 and/or inhibin staining but none was SF1 positive. Most cases in both groups expressed the less specific immunomarkers. SF1 and FOXL2 immunoreactivity in UTROSCT further supports the concept that these tumours demonstrate genuine sex cord-stromal differentiation. While calretinin was the most sensitive UTROSCT marker, staining was usually focal and expression was also seen in two of 10 potential histological mimics. SF1 staining was 100% specific for UTROSCT in this series but this finding should be confirmed in larger studies.

Endometrial stromal sarcoma: morphologic features and detection of JAZF1-SUZ12 and YWHAE FAM22 fusion genes

To study the morphologic features, immunophenotype and significance of expression of JAZF1-SUZ12 and YWHAE-FAM22 fusion genes in endometrial stromal sarcoma (ESS). Fifty-three cases of ESS were retrieved and the pathologic features were reviewed. Immunohistochemical study for estrogen receptor, progesterone receptor, CD10, cyclin D1, smooth muscle actin, desmin and H-caldesmon were carried out using tissue microarray technology. Reverse transcription-polymerase chain reaction (RT-PCR) was applied for detection of expression of JAZF1-SUZ12 and YWHAE-FAM22 fusion genes in 47 cases of ESS and 12 cases of other spindle cell neoplasia in uterus (including 2 cases of undifferentiated sarcoma, 3 cases of leiomyosarcoma, 3 cases of leiomyoma, 4 cases of adenosarcoma and 2 cases of uterine tumor resembling ovarian sex cord tumor). The 53 cases of ESS studied included 43 cases of low-grade ESS and 10 cases of high-grade ESS. As for low-grade ESS, in addition to the classic morphologic features, smooth muscle differentiation was present in 7 cases (16.3%), sex cord-like differentiation in 2 cases (4.7%), rhabdoid differentiation in 1 case (2.3%), clear cell changes in 1 case (2.3%) and schwannoma-like palisading pattern in 1 case (2.3%). As for high-grade ESS, sex cord-like differentiation (1 case), mucinous microcystic changes (1 case) and focal clear cell changes (1 case) were also observed. The expression rate of estrogen receptor, progesterone receptor, CD10, cyclin D1, smooth muscle actin, desmin and H-caldesmon was 86.0%, 81.4%, 74.4%, 2.3%, 23.3%, 23.3% and 4.7% in low-grade ESS, respectively, and was 1/10, 6/10, 6/10, 7/10, 1/10, 1/10 and 0 in high-grade ESS, respectively. RNA extraction was successful in 47 cases of ESS, including 39 cases of low-grade ESS and 8 cases of high-grade ESS. The positive rate of JAZF1-SUZ12 fusion gene was 30.8% (12/39) in low-grade ESS. The positive rate of YWHAE-FAM22 fusion gene was 12.5% (1/8) in high-grade ESS. The 14 control cases were all negative for JAZF1-SUZ12 and YWHAE-FAM22 fusion genes. As uncommon pathologic pattern may occur in both low-grade ESS and high-grade ESS, detection of JAZF1-SUZ1 and YWHAE-FAM22 fusion genes by RT-PCR would be helpful in diagnosis and differential diagnosis of ESS, especially for those tumors which lack typical morphologic features.

Extensive Overgrowth of Sex Cord-Like Differentiation in Uterine Mullerian Adenosarcoma

Sex cord-like differentiation has been well documented in endometrial stromal tumors. On the basis of the extent of sex cord differentiation, uterine stromal tumors with this kind of differentiation have been classified into 2 subgroups of endometrial stromal tumor with sex cord-like elements and uterine tumors resembling ovarian sex cord tumor. When extensive, this differentiation has been accompanied with indolent clinical behavior and rather good prognosis in most cases. Sex cord differentiation has been rarely observed in uterine mullerian adenosarcoma. Only 3 cases of such occurrence have been reported in the English literature. Herein, we report a case of uterine mullerian adenosarcoma extensively overgrown by uterine tumor resembling ovarian sex cord tumor in a young woman. The presence of an ovarian sex cord tumor component has been confirmed by immunohistochemistry. To the best of our knowledge, this is the second report of such a case in the English literature.

Cellular mesenchymal tumors of the uterus: a review emphasizing recent observations.

Cellular mesenchymal tumors of the uterus may be divided in 2 main groups, smooth muscle and endometrial stromal. Among the former, highly cellular leiomyoma is the classic example. This tumor is not infrequently confused with an endometrial stromal tumor due to its often yellow color and soft consistency, dense cellularity, striking vascularity, not uncommon irregular margin and even rarely association with seedling cellular leiomyomas, both mimicking the infiltration of a low-grade endometrial stromal sarcoma. Cellular intravenous leiomyomatosis can also mimic endometrial stromal sarcoma due to their shared intravascular growth. A variety of histologic features typical of cellular smooth muscle including clefts and differing vasculature help in this distinction. Although endometrial stromal tumors are typically highly cellular, recent studies have expanded their spectrum to include those that are less so due to smooth muscle metaplasia, fibrous and myxoid change, and even oxyphilic cytoplasm. A subset now designated high-grade endometrial stromal sarcoma showing a t(10;17) has been characterized to show small epithelioid cells associated with brisk miotic activity, typically being CD10, ER and PR negative, and cyclin D1 positive. These tumors are juxtaposed to areas of fibromyxoid endometrial stromal neoplasia in 50% of cases. An enigmatic category of uterine mesenchymal neoplasms, often densely cellular, are those descriptively referred to as "uterine tumors resembling ovarian sex cord tumors." Their spectrum is briefly noted as is their crucial distinction from stromal sarcoma with sex cord-like differentiation. Other tumors that rarely occur in the uterus that are densely cellular include but are not limited to undifferentiated uterine sarcoma, embryonal rhabdomyosarcoma, primitive neuroectodermal tumor, lymphoma or small cell, or undifferentiated carcinoma. In this essay, I review the most helpful morphologic, immunohistochemical, and/or cytogenetic features in the diagnosis of each one of these entities.

Uterine Tumors Resembling Ovarian Sex Cord Tumor in Postmenopausal Woman.

Uterine tumors resembling ovarian sex cord tumors (UTROSCTs) are a rare group of stromal neoplasms containing prominent sex cord-like elements. Since they were first described in 1945 by Morehead and Bowman [1], no more than 100 such tumors have been reported [2]. In a report by Clement and Scully [3], these neoplasms were divided into 2 groups on the basis of clinical and histologic patterns. The first group (group I) included endometrial stromal tumors with less than 50 % sex cord-like elements, and the second group (group II) included UTROSCTs exhibiting sex cord-like differentiation of more than 50 %. In the latest, according to the World Health Organization classification of uterine neoplasms, UTROSCTs were placed in a miscellaneous category of tumors of the uterine corpus because of their different morphology and benign clinical behaviors [4]. More recently, UTROSCTs have been suggested to be unusual neoplasms of uncertain malignancy with polyphenotypic immunohistochemical expression, characterized by positivity for sex cord, epithelial, and myoid markers [5, 6]. These tumors usually occur in premenopausal or menopausal women. Most patients have symptoms such as abnormal vaginal bleeding, abdominal pain, and enlarged uterus or a palpable uterine mass on physical examination [7]. In most cases, UTROSCT is diagnosed incidentally after hysterectomy for a clinical diagnosis of an endometrial polyp [8, 9] or sometimes leiomyoma [10]. We report a case of UTROSCT in a postmenopausal woman with vaginal bleeding who was diagnosed with uterine sarcoma at a local clinic.

Endometrial stromal tumors with sex cord-like elements: a case report

Endometrial stromal nodules are rare. They represent less than a quarter of endometrial stromal tumors. Clement and Scully described as variants of endometrial stromal nodules two types of tumor ressembling ovarian sex cord tumors. Type I is tumor that resembles focally an ovarian sex cord tumor which can be abbreviated ESTSCLE, or endometrial stromal tumors with sex cord-like elements and type II; uterine tumors with more than 40% sex cord-like differentiation so called UTROSCT for uterine tumor resembling ovarian sex cord tumor. Uterine tumours with sex cord-like differentiation are very rare with only 50 cases reported in the literature so far. The diagnostic is based on microscopic findings. Immunohistochemical tests to elucidate their nature yield variable and polyphenotypic with coexpression of markers of epithelial, myoid and sex cord lineage as well as hormone receptors. We report an additional case of an endometrial stromal tumors with sex cord-like elements in a 48-year-old woman presenting with abnormal mass.

Uterine adenosarcoma with ovarian sex cord-like differentiation: A case report and review of the literature

Objectives To determine the prognosis of uterine adenosarcoma with ovarian sex cord like-differentiation after treatment and to review the literature. Case Report A 47-year-old premenopausal unmarried woman presented with irregular menstrual bleeding and uterine mass. Sonographic examination, suggested two uterine fibroids located in the uterine fundus and cervix measuring 4 × 3 cm and 3 × 3 cm, respectively. Total abdominal hysterectomy with bilateral salpingo-oopherectomy was performed and the histopathology report confirmed the diagnosis of uterine adenosarcoma with ovarian sex cord like-differentiation. The patient received neither chemotherapy nor other adjuvant therapy because the tumor had low malignant potential, and the extent of myometrial invasion was less than half of the whole myometrium. The patient had an uneventful recovery, and no recurrence was detected for 2 years in the follow-up period. Conclusion Uterine adenosarcomas mostly have relatively low malignant potential. Surgery is the optimal standard treatment for patients. Although there is not enough data in the present literature, benign epithelial differentiations, such as sex cord-like elements may reflect the behaviour of the tumour and shows the tendency to have a benign course in most of cases.

Uterine perivascular epitheloid cell tumor (PEComa) with CD117 and PNL2 positivity and entrapped endometriotic glands, mimicking sex-cordlike differentiation

Uterine perivascular epitheloid cell tumor (PEComa) with CD117 and PNL2 positivity and entrapped endometriotic glands, mimicking sex-cordlike differentiation

Diagnostic Utility of theJAZF1/JJAZ1Gene Fusion in Endometrial Stromal Sarcomas and Their Histologic Variants

BACKGROUNDThe diagnosis of endometrial stromal sarcoma (ESS) is often difficult in cases showing diverse histological differentiation or in undifferentiated endometrial sarcoma (UES). Recently, JAZF1/JJAZ1 gene fusion has been described as a defining feature of low-grade ESS (LGESS). However, its prevalence is variably reported, and the diagnostic utility has rarely been examined for cases showing various histological differentiation.METHODSTo test the diagnostic utility of JAZF1/JJAZ1 gene fusion in difficult cases, we compared the prevalence of the JAZF1/JJAZ1 fusion gene in LGESS with and without histological differentiation.RESULTSThe JAZF1/JJAZ1 fusion transcript was detected in 18 of 21 LGESS (85.7%), including 14 classical LGESS (93%), four LGESS with diverse histological differentiation (67%), and two with UES (28.6%). Positive cases included two LGESS with sex cord-like differentiation, one with osseous differentiation, and two UES. LGESS showing smooth muscle differentiation revealed the fusion transcript only in the classic area. Direct sequencing analysis of two LGESS revealed a previously reported breakpoint at t(7;17)(p15;q21).CONCLUSIONSThe JAZF1/JJAZ1 fusion gene was identified in a significant proportion of LGESS showing secondary histological differentiation except in cases with smooth muscle differentiation. Thus, this fusion gene may be useful to confirm the diagnosis in difficult cases of LGESS.

Diverse Phenotypic Profile of Uterine Tumors Resembling Ovarian Sex Cord Tumors

Uterine tumors resembling ovarian sex cord tumors (UTROSCTs) are rare neoplasms thought to be of putative endometrial stromal origin and solely composed of sex cord elements. Our study aimed to delineate the immunophenotype of these tumors and to verify whether their morphology reflects true sex cord-like differentiation. Representative paraffin blocks from 12 UTROSCTs were selected after confirmation of the diagnosis. Cords and/or trabeculae were seen in all tumors, whereas tubules, diffuse areas, and a retiform pattern were present in 9, 6, and 2 cases, respectively. Tumors were stained for sex cord (inhibin, calretinin, WT1, and melan-A), epithelial (KL1 and epithelial membrane antigen), and smooth muscle markers (smooth muscle actin, desmin, smooth muscle myosin heavy chain, h-caldesmon, and histone deacetylase-8), CD10, HMB45, S100, and CD117. Intensity and percentage of staining were recorded. Six out of 12 tumors were positive for sex cord markers (inhibin 3 of 12, calretinin 4 of 12, WT1 4 of 12, and melan-A 3 of 11) with 4 tumors coexpressing more than one marker. Half of the UTROSCTs showed positivity for KL1, with 2 tumors coexpressing epithelial membrane antigen. All but one tumor expressed one or more smooth muscle markers, with smooth muscle actin, desmin and histone deacetylase-8 being most commonly expressed. CD10 was positive in 6 of 12 tumors, CD117 in 4 of 12, and S100 in 2 of 11 tumors, whereas HMB45 was negative in 11 tumors tested. UTROSCTs have a diverse immunohistochemical profile often coexpressing sex cord, epithelial, and smooth muscle markers. The expression of smooth muscle markers in these tumors does not imply a smooth muscle origin as endometrial and sex cord stromal tumors are not infrequently positive for these markers. Positivity for sex cord markers supports a true sex cord/steroid phenotype. Although the immunohistochemical profile of these tumors overlaps with that of endometrial stromal tumors with sex cord-like differentiation as well as ovarian sex cord stromal tumors, the origin of UTROSCT remains uncertain.

Clinicopathologic Features of 2 New Cases of Uterine Tumors Resembling Ovarian Sex Cord Tumors

Uterine neoplasms showing an exclusive sex cord-like differentiation or focal low-grade sarcoma differentiation, designated as uterine tumors resembling ovarian sex cord tumors (UTROSCTs), are rare, with only 48 cases described earlier in international literature. Generally, this entity is characterized by benign behavior. In this study, we report the clinical and pathologic features of 2 peculiar new cases of UTROSCTs. In these examples, the pathologic diagnosis of UTROSCT was made incidentally after the clinical diagnosis of a leiomyoma and endometrial polyp. On examination of small biopsies, the diagnosis was facilitated by specific immunohistochemical analysis using markers for the sex cord component. In 1 of these cases, the patient, because of her young age and her desire to preserve her fertility, was only treated by minimally invasive hysteroscopic surgery. In the other case, the neoplasm seemed to be the consequence of tamoxifen treatment for breast carcinoma. After diagnosis, in this second case, the woman underwent hysterectomy that showed a residue of the tumor and cervical metastasis from the earlier breast carcinoma. The differential diagnosis of UTROSCT and the role of immunohistochemistry in confirming a diagnosis are discussed.

Mullerian Adenosarcoma of the Female Genital Tract

Mullerian adenosarcoma is an uncommon, but not rare, mixed tumor containing a neoplastic but benign or mildly atypical epithelial element and a sarcomatous, usually low-grade, stromal component. The most common site is the uterine corpus but adenosarcoma also occurs in the cervix and ovary and more rarely in the vagina, fallopian tube, arising from peritoneal surfaces, or outside the female genital tract, for example in the intestine. Most uterine cases have a polypoid gross appearance, sometimes resulting in the formation of multiple polyps. Characteristic histologic features include a low power "phyllodes-like" architecture with leaf-like projections lined by a variety of benign Mullerian type epithelia, sometimes with squamous metaplasia. Intraglandular stromal protrusions are a characteristic feature. The stroma may be uniformly cellular but there is typically increased cellularity around the epithelial elements, resulting in the formation of a cambium layer. Using the World Health Organization definition, stromal mitotic activity of 2 or more per 10 high-power fields is required for a diagnosis of adenosarcoma but in practice the diagnosis is made with stromal mitotic activity less than this if the characteristic architecture and cambium layer is present. The stromal component is usually morphologically "low-grade" and of endometrial stromal or fibroblastic type (hormone receptor and CD10 positive). Sometimes it is high grade, resembling undifferentiated sarcoma. Additional features sometimes present include heterologous stromal elements or sex cord-like differentiation. Uterine adenosarcomas are, in general, low-grade neoplasms capable of local recurrence after polypectomy or hysterectomy and much less commonly distant metastasis. The 2 most important adverse prognostic factors, which sometimes coexist, are deep myometrial invasion and sarcomatous overgrowth; the latter is usually associated with morphologically "high-grade" stromal elements with loss of expression of hormone receptors and CD10. Adenosarcoma may be confused with a variety of lesions and one of the main differential diagnoses is adenofibroma in which the stromal component is, by definition, morphologically benign. However, occasional adenofibromas recur or even metastasize. As such, it has been suggested that all adenofibromas should be classified as adenosarcomas, albeit with low-malignant potential. Ovarian adenosarcomas are much more likely to exhibit malignant behavior than their uterine counterparts, probably due to the lack of an anatomic barrier to peritoneal dissemination.

Uterine Tumors Resembling Ovarian Sex Cord Tumors: An Ultrastructural Analysis of 13 Cases

Uterine tumors resembling ovarian sex cord tumors (UTROSCT) are tumors of unclear histogenesis. The authors analyzed the ultrastructural features of 13 UTROSCT and correlated the findings with their immunohistochemical profile. Features included cells with frequent organoid, nested or cord-like arrangement (8), lumen formation (2; one of which showed surface microvilli), nuclei with irregular indentations (8), intermediate filaments (13), prominent paranuclear aggregates (5), cell junctions (9), desmosome-like junctions (2), tonofilaments (2), basal lamina (1), and cytoplasmic lipid droplets (7; prominent in 3). No dense bodies, subplasmalemmal densities or pinocytotic vesicles were seen. Ultrastructural epithelial differentiation was present in 2 tumors (positive for keratin or epithelial membrane antigen). Prominent lipid droplets correlated with sex cord markers positivity in 2 tumors. Ultrastructural features of smooth muscle differentiation were lacking and abundant paranuclear filaments did not correlate with myoid markers. UTROSCT are polyphenotypic neoplasms ultrastructurally with focal epithelial and variable sex cord-like differentiation. These findings suggest that UTROSCT may result from divergent differentiation in endometrial stromal tumors or represent a distinct group of uterine tumors with sex cord-like differentiation that are closer in histogenesis to ovarian sex cord stromal tumors.

Uterine Tumors Resembling Ovarian Sex Cord Tumors

Uterine tumors resembling ovarian sex cord tumors (UTROSCT) are distinguished into two separate groups: endometrial stromal tumors with sex cord-like elements (Group I), which have an unfavorable prognosis; and UTROSCT proper (group II), with more than 40% sex cord-like differentiation and less endometrial component, which are biologically less aggressive than the tumors of the other group. We report the case of a young woman with UTROSCT treated by minimally invasive hysteroscopic surgery. This is one of the few cases reported in the literature that have been managed conservatively.

Calretinin

The utility of calretinin was first described in the diagnosis of mesothelioma. In the female genital tract, calretinin was initially reported in Wolffian remnants and related lesions and later used in the diagnosis of sex cord stromal tumors of the ovary, endometrial stromal tumors with sex cord-like differentiation, and uterine tumors resembling sex cord tumors of the ovary. This review discusses calretinin expression in normal tissues of the female genital tract and highlights its potential utility in the diagnosis of these subsets of neoplasms with emphasis to tumors that may constitute a problem in their differential diagnosis. In particular, the limited utility of calretinin in the diagnosis of sex cord stromal tumors of the ovary, in the differential diagnosis between mesothelioma and serous tumors involving the ovary and/or peritoneum, and in the differential diagnosis between Wolffian lesions and endometrial carcinoma are addressed.

Mullerian Adenosarcoma

Mullerian adenosarcomas are rare mixed tumors of low malignant potential that occur mainly in the uterus and also in extrauterine locations. Microscopically, they may be difficult to distinguish from adenofibromas. In this clinicopathologic study of 55 adenosarcomas, the mean patient age was 50 years (range: 13 to 83 y). Thirty-seven tumors were of the uterine corpus, 11 of the cervix, 4 of the ovary, and 1 each of the fallopian tube, vagina, and Douglas peritoneum. Abdominal pain and vaginal bleeding were the usual complaints. Treatment was known in 50 patients: 10 had polypectomy, 1 cone biopsy, and 39 hysterectomy, which was accompanied by bilateral salpingo-oophorectomy in 24 and lymphadenectomy in 4. Five patients had radiotherapy and 2 of them had chemotherapy. Stage was known in 41 cases. Of 30 tumors of the uterine corpus, 17 were stage IA, 11 stage IB, 1 stage IC, and 1 stage IIIC. Four cervical tumors were stage IB. Three of the 4 ovarian tumors were stage IA and the other was stage IIIC. The tumor of the fallopian tube was stage IC, and the tumors of the vagina and recto-uterine pouch were confined to their site of origin. Most uterine tumors were polypoid masses ranging from 1 to 20 cm (mean: 6.5 cm). Microscopically, sarcomatous overgrowth was found in 18 cases (33%), heterologous elements in 13 (24%), and sex cordlike differentiation in 7 (13%). Fourteen of 30 uterine tumors (47%) had myometrial invasion that was minimal in 5, involved one-third of the myometrial thickness in 7, and more than 50% in 2. Of 4 cervical tumors, 2 were endocervical polyps, 1 invaded one-third of the cervical wall, and the other invaded its full thickness. Follow-up information (2 mo to 18 y; average: 7.5 y) was available in 29 patients. Six developed metastases and 5 of them died of tumor. Four had adenosarcomas with sarcomatous overgrowth; however, the other 2 patients had typical low-grade adenosarcomas of the uterine corpus and cervix, respectively, exhibiting only mild nuclear atypia of the stromal component and </=2 mitotic figures/10 high power fields. Both were initially underdiagnosed as adenofibromas. The finding of such cases, which raises the controversy of whether or not adenofibroma exists as a tumor entity, prompted us to make a comparative immunohistochemical analysis of 23 typical adenosarcomas, 8 adenosarcomas with sarcomatous overgrowth, and 29 benign and malignant related lesions, including 7 clinically benign adenofibromas. Adenosarcomas with sarcomatous overgrowth showed strong immunoreaction for Ki-67 and p53 and loss of CD10 and progesterone receptors immunostaining; in contrast, the immunoreaction for these tumor markers in typical adenosarcomas without sarcomatous overgrowth was similar to that of adenofibromas associated with favorable outcome and other benign lesions such as endometrial polyps and endometriosis. These findings suggest that some of the tumors currently classified as adenofibromas, on the basis of their low mitotic count and lack of significant nuclear atypia, are, in fact, well-differentiated adenosarcomas.