Mesenchymale Uterustumoren

Uterine stromal neoplasms are classified into endometrial stromal nodules and stromal sarcomas, as well as undifferentiated sarcomas. The two former groups demonstrate identical histological composition, consisting of small monomorphous cells with scant cytoplasm and round nuclei and typically contain numerous arteriolar-type vessels. Stromal tumors are distinct from stromal nodules by virtue of their myometrial and vascular invasion. Undifferentiated sarcomas consist of polymorphic cells and lack any cytological similarity to the stroma of normal proliferative endometrium. There is no smooth or striated muscle differentiation. Adenosarcomas are mixed neoplasms with a low grade stromal sarcoma component containing benign glands, which are surrounded by condensed neoplastic stroma. Typical uterine tumors resembling ovarian sex cord tumors (UTROSCT Type2) show predominant sex cord differentiation in a well circumscribed nodule. Focal sex cord differentiation may occur in stromal nodules and stromal sarcomas (UTROSCT Type2).     

Low-grade endometrial stromal sarcoma with intracardiac extension. Evolution of extensive smooth muscle differentiation and usefulness of immunohistochemistry for its recognition and distinction from intravenous leiomyomatosis.

This case, a rare example of low-grade endometrial stroma sarcoma with extensive smooth muscle differentiation which extended to the inferior vena cava and cardiac chambers closely resembling intravenous leiomyomatosis grossly and microscopically, illustrates the importance of extensive sectioning and the usefulness of immunohistochemistry. Although spindle cell components arranged in interlacing bundles consistent with smooth muscle differentiation were recognizable in the primary tumor (on retrospective review), extensive smooth muscle differentiation in the recurrent tumors masked prototypical morphologic features of stromal sarcoma and only small neoplastic stromal components were preserved in limited areas, leading to initial failure to distinguish the lesion from intravenous leiomyomatosis. The immunophenotyping disclosed two distinct cell populations in the tumor: i.e. vimentin-positive and smooth muscle marker negative stromal cells, and vimentin-negative spindle-shaped desmin-positive smooth muscle cells. Our observation suggests that the predominance of a smooth muscle component in such a tumor can be misleading and does not always warrant a diagnosis of intravenous leiomyomatosis, nor does it predict a benign clinical course. This case also provides an insight into the relationship of the endometrial stroma and myometrium, and their cell of origin and the histogenesis of endometrial stromal sarcoma.     

Myogenous phenotype of epithelial-like areas in endometrial stromal sarcomas

Approximately 25% of low-grade endometrial stromal sarcomas of the uterus contain areas of epithelial-like differentiation, which are often reminiscent of ovarian sex-cord tumors. It has been suggested that these areas may represent attempted differentiation toward either uterine glands or smooth muscle. To investigate these two possibilities, we examined the histologic and immunohistochemical features of 26 low-grade endometrial stromal sarcomas. Eight tumors had epithelial-like differentiation, which in some tumors was so prominent as to suggest a purely epithelial neoplasm. Areas typical of endometrial stromal sarcoma were vimentin positive, whereas epithelial-like differentiation expressed vimentin and the muscle markers muscle-specific actin and desmin, as well as cytokeratin, but not the epithelial marker epithelial membrane antigen. Epithelial-like differentiation in low-grade endometrial stromal sarcoma is not uncommon and, based on our immunohistochemical results after comparison with normal controls, epithelial-like differentiation has a myogenous rather than an epithelial phenotype.     

Adenosarcoma of the Uterus with Extensive Smooth Muscle Differentiation: Ultrastructural Study and Review of the Literature

Four cases of Mullerian adenosarcoma were studied by light and electron microscopy and immunohistochemistry. All 4 cases showed the histologic characteristics of adenosarcoma with benign endometrial glands and a malignant stroma. Ultrastructurally, the epithelial component in all cases had the appearance of proliferative endometrial glands, and the malignant mesenchymal cells showed features of endometrial stroma. A distinct basal lamina separating glands from stroma was present. In addition, 2 of the cases showed extensive smooth muscle differentiation which was associated with sarcomatous overgrowth. The smooth muscle features were confirmed by immunohistochemistry. Multiple theories of the histogenesis of this tumor are discussed.     

Endometrial stromal nodule with smooth muscle differentiation

Uterine tumors composed of a prominent component of smooth muscle and endometrial stroma (so-called stromomyoma) are distinctly uncommon. This article describes the morphological features of one such tumor discovered as an incidental finding in a hysterectomy specimen of a 49-year-old lady with a clinical diagnosis of dysfunctional uterine bleeding. Morphological and immunohistochemical (IHC) evaluation were performed and a final diagnosis of endometrial stromal nodule with smooth muscle differentiation was rendered.     

The leiomyomatous stroma in renal cell carcinomas is polyclonal and not part of the neoplastic process

Some renal epithelial neoplasms, such as renal angiomyoadenomatous tumor, clear cell papillary renal cell carcinoma and renal cell carcinoma with smooth muscle stroma, contain a variably prominent smooth muscle stromal component. Whether or not this leiomyomatous stroma is part of the neoplastic proliferation has not been firmly established. We studied the clonality status of 14 renal cell carcinomas with a prominent smooth muscle stromal component (four renal angiomyoadenomatous tumors/clear cell papillary carcinomas, five clear cell carcinomas, two papillary carcinomas, and three renal cell carcinomas with smooth muscle rich stroma) using the human androgen receptor assay (HUMARA). We found the leiomyomatous stromal component in all analyzable (8/14) cases to be polyclonal and therefore reactive rather than neoplastic. Based on morphological observations, we propose that the non-neoplastic leiomyomatous stromal component is likely derived from smooth muscle cells of large caliber veins located at the peripheral capsular region or within the collagenous septae of the tumors.     

An endometrial stromal tumor with osteoclast-like giant cells

Endometrial stromal tumors (ESTs) of the uterine corpus have a striking propensity to display diverse morphological variations, including sex cord-like, smooth muscle, or skeletal muscle differentiation; fibrous change; myxoid change; or bland endometrioid-type glands. They may also contain rhabdoid, foam, clear, or epithelioid/granular cells among others. Recently, we have encountered an EST showing smooth muscle differentiation and osteoclast-like giant cells that were predominantly concentrated in the areas showing smooth muscle differentiation. Osteoclastlike giant cells have not been previously reported in EST to our knowledge; thus, this finding expands the morphological spectrum of these tumors. In addition, although the level of infiltration at the peripheries of the tumor exceeded that allowable under the Tavassoli and Norris criteria for stromal nodules, it did not reach the classic permeative infiltration generally associated with endometrial stromal sarcomas. Historical, prognostic, and diagnostic aspects of margins in EST, especially in those borderline cases such as ours, are also discussed.     

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.     

Myxoid mesenchymal tumors of uterus: endometrial stromal and smooth muscle tumors, myxoid variant

Four myxoid variant of uterine mesenchymal tumors are reported. One was a low grade stromal sarcoma with infiltrative margins and the others were well circumscribed tumors corresponding to an endometrial stromal nodule and two leiomyomas. They were hypocellular neoplasms composed of stellated cells with an abundant Alcian Blue positive myxoid matrix. The myxoid nature of the neoplasms obscured their cellular nature and made the distinction between smooth muscle and endometrial stromal tumors difficult. Endometrial stromal tumors, showed very focal areas of small basophilic cells, characteristic of endometrial stroma. The diagnosis was based on the presence of a spiral arteriolar network, a CD10 positivity as well as the absence of h-caldesmon and desmin expression. The two myxoid leiomyomas showed more spindle cells and a desmin expression while h-caldesmon was negative and CD10 focally positive in both cases. Myxoid variant of endometrial stromal tumors does not necessarily exhibit the typical morphology of endometrial stroma. They may demonstrate morphological features of smooth muscle tumors in the uterus. Also, myxoid changes in uterin smooth muscle tumors may modify the classical immunoreactivity of smooth muscle markers in these tumors and make it difficult to distinguish between benign and malignant neoplasms. An immunohistochemical panel of antibodies including CD10, h-caldesmon and desmin may help in establishing the correct diagnosis.     

Müllerian Adenosarcoma of the Uterus: Literature Review,Case Report,and Ultrastructural Observations

This is a report of a transmission and scanning electron microscopic examination of a müllerian adenosarcoma. The neoplasm had the characteristic pattern of benign neoplastic glands with focal squamous metaplasia and a sarcomatous stroma. Ultrastructurally, both mesenchymal and epithelial elements were identified. The mesenchymal components were Ultrastructurally identical to those present in endometrial stromal sarcomas, including active collagen synthesis. The epithelial component resembled benign endometrial glands, and there was significant secretory activity as evidenced by prominent cytoplasmic glycogen collections.     

Clear cell renal cell carcinoma with smooth muscle stroma

A recent publication described 5 unusual clear cell renal tumors with prominent smooth muscle stroma that were characterized only by immunostaining. We report 3 additional tumors composed of clear cell renal cell carcinoma intimately admixed with abundant smooth muscle stroma. Epithelial differentiation of the malignant clear cell components and smooth muscle differentiation of the benign spindle cell stroma was confirmed by the immunostaining profiles and by electron microscopy. Fluorescence in situ hybridization analysis of chromosome 3 showed loss of the entire chromosome in 2 cases and loss of 3p in the third case. We therefore interpret these tumors as unique low-grade variants of clear cell renal cell carcinoma that have induced a prolific metaplastic stromal reaction. Extensive tissue sampling and immunostaining are recommended to distinguish cases with an extensive smooth muscle component from morphologically similar but benign lesions including angiomyolipoma, leiomyoma, or mixed epithelial and stromal tumor of the kidney.     

Two Previously Unemphasized Features of Endometriosis: Micronodular Stromal Endometriosis and Endometriosis with Stromal Elastosis

This report draws attention to two unusual features of the stromal component of endometriosis that can create problems in diagnosis. One of these is the exclusive presence of endometriotic stroma, so-called stromal endometriosis, that can occasionally take the form of microscopic nodules of endometriotic stroma on the pelvic peritoneum and other locations. This finding, which we refer to as a micronodular stromal endometriosis, can be overlooked entirely or lead to confusion with peritoneal involvement by low-grade endometrial stromal sarcoma. The other finding we describe is the presence of a prominent elastotic stromal response to endometriosis that can occasionally obscure or even focally obliterate the typical endometriotic stroma. This finding, although nonspecific, can be a diagnostic clue to the presence of endometriosis, especially when accompanied by the presence of the typical endometriod glands of that lesion. Int J Surg Pathol 8(3):223-227, 2000     

Ultrastructure of an Endometrial Stromal Nodule with Skeletal Muscle

The ultrastructural appearance of an endometrial stromal nodule with prominent smooth and skeletal muscle differentiation is described. This is the first reported case of endometrial stromal nodule with a heterologous skeletal muscle component and emphasizes the value of electron microscopy and its correlation with immunohistochemistry in the study of rare or complex lesions.     

CD10 immunostaining distinguishes atypical polypoid adenomyofibroma (atypical polypoid adenomyoma) from endometrial carcinoma invading the myometrium

The major differential diagnostic problem presented by atypical polypoid adenomyofibroma (atypical polypoid adenomyoma) (APA), which usually affects young women, is the exclusion of well-differentiated endometrial carcinoma invading the myometrium. This distinction, however, is of great clinical importance from the standpoint of treatment because reproductive conservation is feasible for patients with APA. Recently, CD10, known to be a marker of endometrial stromal cells, was reported to be also expressed in cells immediately surrounding the neoplastic glands invading the myometrium [Am J Surg Pathol 27 (2003) 786-789; Mod Pathol 16(1) (2003) 22-27]. However, CD10 expression in the myofibromatous component of APA has not been previously examined in the literature. We therefore decided to examine whether the CD10-immunostaining pattern in APA is different from that in myoinvasive carcinoma. Furthermore, we also attempted to obtain any histopathologic findings that may offer some insight regarding the histogenesis of APA. Seven cases of APA were immunostained for CD10 using curettage or polypectomy specimens, in addition to hysterectomy specimens in 1 case. Areas with more fibrotic rather than muscular stroma were focally observed in 4 cases. The pattern of staining was compared with hysterectomy specimens taken from 19 cases in which well- to moderately differentiated endometrioid adenocarcinoma had deeply invaded the myometrium (outer two thirds of the myometrium) but was not associated with adenomyosis. In 6 of 7 cases of APA, CD10 was never expressed in the myofibromatous stromal components. In 1 case of APA, the fascicles of fibrotic and muscular mesenchymal cells in the interglandular areas were focally and weakly positive for CD10. All 19 myoinvasive carcinomas expressed CD10 to some extent in cells immediately surrounding the neoplastic myoinvasive glands (fringe-like staining pattern). The proportion of the myoinvasive nests immediately surrounded by CD10-positive mesenchymal cells was as follows: mean, 74%; median, 80%; minimum, 5%; maximum, 100%. The fringe-like CD10-staining pattern was not observed in APA. Furthermore, we identified a gradual transformation from preexisting endometrial stromal cells (CD10 positive) into the typical myofibromatous stromal component (CD10 negative) of APA in 1 case. In conclusion, this study demonstrated differences in the CD10 immunoreactivity or immunostaining pattern between the stromal components of APA and myoinvasive endometrial carcinoma. This difference should lead to a more accurate diagnosis of APA (pseudo-myoinvasive lesion). Furthermore, the histogenesis of APA may perhaps be explained by "myofibromatous metaplasia" of the endometrial stromal cells.     

Malignant phyllodes tumor of the prostate. A case report with immunohistochemical and ultrastructural studies.

Phyllodes tumor of the prostate is a rare neoplasm with cellular or sarcomatoid stroma and hyperplastic glands. This lesion shares many histologic features with cystosarcoma phyllodes of the breast. Although a malignant variant of phyllodes tumor of the prostate has been described, the majority of cases have been clinically benign. We report an unusual case of phyllodes tumor of the prostate in which the stromal component underwent malignant degeneration, a finding not previously described (to our knowledge). Immunohistochemical and ultrastructural studies demonstrated smooth-muscle differentiation of the stromal cells.     

Uterine endometrial stromal sarcoma with rhabdoid and smooth muscle differentiation.

Uterine and extrauterine tumors composed of cells featuring endometrial stromal cells often show ovarian sex cord-like structures and smooth muscle differentiation. A few cases of endometrial stromal tumors showing rhabdoid differentiation have been reported. The present case is a 20-year-old woman with endometrial stromal sarcoma that had sex cord-like structures, smooth muscle components and rhabdoid differentiation.     

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.     

Mixed epithelial and stromal tumour (MEST) of the kidney: report of 14 cases with male and PEComatous variants and proposed histopathogenesis

AIMS: This article adds new cases and variants of MEST with discussion of the histopathogenesis. METHODS AND RESULTS: Fourteen MEST were originally diagnosed as cystic nephroma which represents an incidence of 1.6% of renal neoplasms in adults. In females, the stromal component showed areas of müllerian differentiation with positive immunoreactivity for oestrogen (ER) and progesterone receptors (PR) and CD10. Immunoreactivity for HMB45 was identified in a single case having a leiomyomatous appearance. The epithelial component displayed features of müllerian epithelium and reactive renal tubular cells. In two male cases, MEST consisted of fibrous and smooth muscle stroma and cysts lined only by reactive renal tubular cells. Immunoreactivity for ER and PR was focal and weak. CONCLUSIONS: MEST represents a tumour developing from müllerian-like stromal cells in the kidney. The neoplastic stroma encroaches on the renal tubules and has the potential to stimulate the growth of the renal tubules by contact, with development into cysts. Furthermore, the müllerian stroma likely induces the renal tubules to differentiate into müllerian-like epithelium. Melanocytic differentiation of the stroma may occur which represents the PEComatous variant. MESTs in males were histopathologically slightly different from those in females due to the different hormonal milieu.     

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.     

Low-grade endometrial stromal sarcoma with an extensive epithelial-like element

A case of low-grade endometrial stromal sarcoma with extensive epithelial-like element (ELE) is reported. This tumor was composed of classical endometrial stromal sarcoma (CESS) showing diffuse proliferation, and ELE occupying approximately 72% of the tumor mass. On immunohistochemistry, ELE was negative for sex-cord differentiation markers, and was positive for myogenic markers used in our investigation, and had a particularly prominent positivity for alpha-smooth muscle actin within the ELE. Therefore, it was considered that ELE showed no true sex cord feature, but smooth muscle differentiation. Moreover, ELE was also positive for CD10, suggesting that it was derived from CESS. It has been reported that there is a distinct clinical behavior between endometrial stromal tumors with abundant ELE and those with limited ELE. In the present case, the Ki-67 labeling index was markedly higher in CESS than in ELE. Therefore, a difference in cell proliferative activity between ELE and CESS might underlie a different clinical prognosis.