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Background
These are very common benign tumors arising within the myometrium. It is the most common tumor of women and the most common tumor of the uterus. These tumors may present with pain, irregular and excessive uterine bleeding, urinary disturbances, or constipation. These tumors sometimes declare themselves during pregnancy and may be associated with abruptio placentae, pain, and premature labor. A manual examination may reveal these tumors. In the past, a hysterectomy was often performed. Today, selective removal of some of the tumors (myomectomy) may be performed. In addition, laser surgery and hormonal ablation have provided women with alternatives other than hysterectomies.
The pathologist is often called to the operating room to open a uterus which is filled with leiomyomas. If there is any grossly suspicious area within the leiomyoma, it will be noted and a frozen section may be performed. The most sinister differential diagnoses that must be excluded include a leiomyosarcoma and an endometrial stromal sarcoma.
OUTLINE
EPIDEMIOLOGY CHARACTERIZATION SYNONYMS Fibroids INCIDENCE Occurs in 20-40% of women over the age of 30 years
Rare <18 years
Uncommon in post menopausal patients
PATHOGENESIS CHARACTERIZATION Probably hormonally sensitive growth Tumors rare before menarche and usually regress after menopause
Occasional rapid growth during pregnancy and clomiphene and progestin treatment
Regression of tumors following gonadotropin-releasing hormone agonists
Increased mitotic activity during the secretory phase of menstrual cycle
Estrogen and progesterone receptors on leiomyoma celsCHROMOSOMAL ALTERATIONS
- Analysis of Allelic Loss as an Adjuvant Tool in Evaluation of Malignancy in Uterine Smooth Muscle Tumors.
Esposito NN, Hunt JL, Bakker A, Jones MW.
From the *Division of Anatomic Pathology and daggerMolecular Anatomic Pathology Laboratory, Department of Pathology, and double daggerDepartment of Pathology, Division of Anatomic Pathology, Magee-Womens Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA.
Am J Surg Pathol. 2006 Jan;30(1):97-103. Abstract quote
Uterine smooth muscle tumors of uncertain malignant potential (STUMPs) are difficult both from the diagnostic and patient management standpoint because they cannot be classified as benign or malignant by conventional histologic criteria.
This study's aim was to determine the diagnostic utility of allelic imbalance (AI) analysis in uterine smooth muscle tumors. Using microdissection and genotyping, we tested 5 leiomyomas, 6 STUMPs, and 10 leiomyosarcomas with follow-up for AI across a panel of seven tumor suppressor genes (p16, p21, p53, VHL, XRCC3, RB, and NM-23). None of the 6 patients with STUMP experienced recurrent disease, whereas 8 of the 10 patients diagnosed with leiomyosarcoma died of disease at follow-up. The mean frequency of allelic loss (FAL) for leiomyomas (18%) was not significantly different from that of STUMPs (21%) (P = 1), whereas leiomyosarcomas displayed a significantly higher FAL (52%) than both leiomyomas (P = 0.001) and STUMPs (P = 0.002). Loss of NM-23, a reported tumor metastasis suppressor gene, was found only in leiomyosarcomas (5 of 9, or 56%), and 4 of 5 (80%) of these were the only cases that demonstrated distant metastases (P = 0.04). Additionally, an FAL of >50% correlated with both NM-23 loss (P = 0.008) and distant metastatic disease (P = 0.04).
In conclusion, leiomyomas and STUMPs displayed similar mean FALs and all were clinically benign, whereas uterine leiomyosarcomas had significantly higher frequencies of allelic loss than both leiomyomas and STUMPs. Molecular profiling may thus provide a valuable tool in assessment of malignancy in uterine smooth muscle tumors. Additionally, NM-23 is a promising candidate gene for determination of metastatic potential in these tumors.
PLATELET DERIVED GROWTH FACTOR
Relationship between platelet-derived growth factor expression in leiomyomas and uterine volume changes after gonadotropin-releasing hormone agonist treatment.Di Lieto A, De Rosa G, De Falco M, Iannotti F, Staibano S, Pollio F, Scaramellino M, Salvatore G.
Department of Obstetrical-Gynaecological and Urological Science and Reproductive Medicine and the Department of Biomorphological and Functional Science, Pathology Section, University Federico II, Naples, Italy.
Hum Pathol 2002 Feb;33(2):220-4 Abstract quote The unopposed estrogen effect is the main cause of leiomyoma growth and is at the basis of the clinical use of gonadotropin-releasing hormone (GnRH) agonists. Platelet-derived growth factor (PDGF) has been indicated as the main growth factor involved, in vitro in the proliferation response of leiomyoma smooth muscle cells to estrogen stimulation.
The aim of this article is to evaluate the mitogenic action of PDGF in vivo by studying the relationship between PDGF expression in leiomyomas and post-GnRH analogue treatment changes in uterine volume. Thirty-nine patients suffering from uterine leiomyomas were treated with leuprorelin acetate depot 3.75 mg for three cycles; 31 untreated patients were enrolled as control group. Uterine volume was determined twice by ultrasonography in each patient, the first time at admission and the second time after treatment in the study group and after 3 months in the control group. The change in the uterine volume was then evaluated. Patients underwent surgery, and PDGF immunohistochemical detection was performed on the obtained fibroid samples. Uterine volume decreased significantly after treatment, whereas just a poor modification was found in the controls. The decrease in the uterine volume was found to be statistically related to PDGF expression. Thus PDGF levels decreased in treated patients as compared with controls.
The decreased PDGF production in leiomyomas after GnRH analogue treatment and the relationship between decreased PDGF expression and greater shrink age in uterine volume suggest that PDGF might have a mitogenic action on leiomyomas in vivo.
TUBERIN
- Expression profile of tuberin and some potential tumorigenic factors in 60 patients with uterine leiomyomata.
Wei J, Chiriboga L, Mizuguchi M, Yee H, Mittal K.
1Department of Pathology, New York University School of Medicine, New York, NY, USA.
Mod Pathol. 2004 Oct 01; Abstract quote
Human uterine leiomyomata are the most common tumors in women of reproductive age. The pathogenesis of leiomyomata remains unknown. An animal model of Eker rats with deleted tuberous sclerosis complex gene 2 (tuberin) shows increased incidence of leiomyomata. The role of tuberin in human leiomyomata is unknown.
In this study, we designed a tissue microarray with tissue cores of leiomyomata and the matched myometrium from 60 hysterectomy specimens. We examined the expression of tuberin and tuberous sclerosis complex gene 1 product hamartin, proteins of the insulin-signaling pathway, steroid receptors and some of their cofactors, and human mobility group gene A2 by immunohistochemistry. We found that nearly half of the cases displayed either reduction or loss of tuberin in leiomyomata compared with matched normal myometrium. No change of hamartin was noted. Furthermore, a significant reduction of glucocorticoid receptor was found in leiomyomata with reduced tuberin. The proteins insulin like growth factor 1, insulin-like growth factor receptor beta, AKT kinase, and phosphatidylinositol 3-kinase were upregulated. Nearly half of leiomyomata show upregulation of human mobility group gene A2, along with the steroid receptor cofactors.
Our findings suggest that there are two broad groups of uterine leiomyomata. One group is associated with an alteration of tuberin and glucocorticoid receptor. The other group is associated with upregulation of human mobility group gene A2 and steroid receptor cofactors.
GROSS APPEARANCE/
CLINICAL VARIANTSCHARACTERIZATION General Solitary or multiple
Well circumscribed tumors with firm white cut surface with whorled fasciclesOccasionally may be pedunculated
Hemorrhage, torsion, necrosis, calcifications, and myxoid degenerative changes are common
BENIGN METASTASIZING LEIOMYOMA
- Benign metastasizing leiomyoma: clonality, telomere length and clinicopathologic analysis.
Patton KT, Cheng L, Papavero V, Blum MG, Yeldandi AV, Adley BP, Luan C, Diaz LK, Hui P, Yang XJ.
1Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
Mod Pathol. 2006 Jan;19(1):130-40. Abstract quote
Benign metastasizing leiomyoma is a rare condition affecting women with a history of uterine leiomyomata and is characterized by multiple histologically benign pulmonary smooth muscle tumors. Speculations on its pathogenesis include a benign uterine leiomyoma colonizing the lung, a metastatic low-grade uterine leiomyosarcoma, and primary pulmonary leiomyomatosis.
To elucidate its pathogenesis, we analyzed the clinical, pathological and immunohistochemical features, clonality, and telomere length of multiple lung and uterine tumors in three patients with benign metastasizing leiomyoma. In all cases, pulmonary tumors had benign histology and immunohistochemical profiles (estrogen receptor positive, progesterone receptor positive, and very low proliferative index) identical to uterine leiomyoma. In eight tumors from three patients, clonality was assessed by analyzing the variable length of the polymorphic CAG repeat sequence within the human androgen receptor gene. In the two informative patients pulmonary and uterine tumors showed identical patterns of androgen receptor allelic inactivation, indicating that they were clonal. The telomere length measured by fluorescence in situ hybridization in pulmonary leiomyomas of all three patients were either long or very long and were identical to the uterine counterparts, indicating significant telomere shortening is not a crucial step for developing metastases.
Our evidence supports the notion that benign metastasizing leiomyoma is clonally derived from benign-appearing uterine leiomyomas.COTYLEDONOID Cotyledonoid Leiomyoma
A Benign Uterine Tumor With Alarming Gross Appearance
W. Cheuk, MBBS, John K. C. Chan, MBBS, FRCPath, and John Y. S. Liu, MBBS, MRCOGFrom the Departments of Pathology (Drs Cheuk and Chan) and Obstetrics and Gynecology (Dr Liu), Queen Elizabeth Hospital, Hong Kong
Arch Pathol Lab Med 2002;Vol. 126, No. 2, pp. 210–213. Abstract quote
Cotyledonoid leiomyoma or “grapelike” leiomyoma is a very rare tumor among the ever-expanding repertoire of growth variants described in benign uterine leiomyoma.We report a case of cotyledonoid leiomyoma in a 55-year-old woman who presented with menorrhagia and uterine prolapse. A large multinodular fungating tumor adhering to the right posterolateral wall of the uterus and extending to the broad ligament was discovered at vaginal hysterectomy. With a provisional diagnosis of sarcoma, total hysterectomy and bilateral salpingo-oophorectomy were performed. Postoperatively, the patient was well with no evidence of recurrence at 14 months.
Pathologic examination revealed a 10-cm, red-brown tumor that comprised multiple bulbous processes protruding over the uterine surface, in continuity with a dissecting intramyometrial component. It was composed of fascicles and nodules of bland-looking smooth muscle cells with prominent perinodular hydropic degeneration. Coagulative necrosis, mitoses, and nuclear atypia were absent.
Cotyledonoid leiomyoma apparently results from a combination of several uncommon growth patterns operating together, including subserosal growth, dissecting growth, and perinodular hydropic degeneration. Increased awareness of this grossly alarming variant of benign uterine leiomyoma can help avoid overtreatment.
PARISITIC Pedunculated tumors lose connection and the stalk is severed with the tumor becoming adherent to other pelvic organs
HISTOLOGICAL TYPES CHARACTERIZATION General Well circumscribed border, not infiltrative
Smooth muscle cells arranged in anastomosing whorled fascicles of uniform fusiform cells
VARIANTS Bizarre (Symplastic) Pleomorphic giant cells focally present Cellular Highly cellular tumor which still retains well circumscribed nature of leiomyoma
Lacks mitotic figures or cytologic atypiaCotyledonoid
Cotyledonoid hydropic intravenous leiomyomatosis: a new variant leiomyoma.Jordan LB, Al-Nafussi A, Beattie G.
Department of Pathology, Medical School Building, University of Edinburgh, Edinburgh, UK, Obstetric and Gynaecology Department, St John's Hospital, Livingston, UK.
Histopathology 2002 Mar;40(3):245-52 Abstract quote Cotyledonoid hydropic intravenous leiomyomatosis: a new variant leiomyoma
Aims: We present the histopathological findings of a series of six cases of a benign uterine smooth muscle tumour with an unusual growth pattern.
Methods and results: All cases have the appearances of the recently described dissecting (cotyledonoid) leiomyoma. In addition, three of these lesions demonstrate the features of intravenous leiomyomatosis with varying degrees of hydropic degeneration.
Conclusions: This combination of phenotypes has not previously been described within the literature; therefore we propose that these are classified as examples of 'cotyledonoid hydropic intravenous leiomyomatosis', a new variant of unconventional leiomyoma
EMBOLIZATION CHANGES
- Uterine arterial embolization with tris-acryl gelatin microspheres: a histopathologic evaluation.
Weichert W, Denkert C, Gauruder-Burmester A, Kurzeja R, Hamm B, Dietel M, Kroencke TJ.
Institute of Pathology, Charite University Hospital, Berlin, Germany.
Am J Surg Pathol. 2005 Jul;29(7):955-61. Abstract quote
Uterine artery embolization (UAE) as an alternative to surgery for the treatment of uterine fibroids and adenomyosis uteri became increasingly popular. While the clinical success of this new treatment strategy is without doubt, there is still considerable uncertainty with respect to the morphologic changes induced by UAE.
In this study, a total of 173 women were treated with UAE using tris-acryl gelatin microspheres (TGMS), a new particulate spherical embolic agent, for either symptomatic adenomyosis or leiomyoma. Surgical specimens of 8 women who underwent subsequent myomectomy or hysterectomy were evaluated by conventional histology and immunohistochemistry.
TGMS were readily apparent in both macroscopy and routine histology. In patients with fibroids, TGMS accumulated in medium-sized vessels in the direct tumor vicinity, a minor fraction of particles was detected in the outer half of the myometrium and within leiomyomata. In patients with adenomyosis, a random distribution of TGMS was noted throughout the outer half of the myometrium. Freshly infused particles occluded the respective arteries without a significant tissue reaction. In the course of time, a granulomatous foreign body reaction in the vicinity of particles occurred, eventually followed by complete vessel destruction. Leiomyoma treated with UAE showed either hyaline necrosis, coagulative necrosis, or no change at all. Foci of adenomyosis remained unaltered.
In conclusion, after UAE with TGMS, particles were identified predominately but not exclusively at the periphery of fibroids. Pathologists must be aware of the morphologic changes induced by UAE in leiomyoma to avoid misinterpretation of induced tissue alterations as signs of malignant tumor growth.
Pathologic features of uteri and leiomyomas following uterine artery embolization for leiomyomas.Colgan TJ, Pron G, Mocarski EJ, Bennett JD, Asch MR, Common A.
Am J Surg Pathol 2003 Feb;27(2):167-77 Abstract quote The objectives of this study were to identify the presence/absence and location of any embolic material and to describe the morphologic appearance of the leiomyoma and adjacent tissues of cases undergoing surgical intervention following uterine artery embolization (UAE) for leiomyomas.
A total of 555 women underwent UAE using polyvinyl alcohol particles (PVA) in a multicenter clinical trial. The histopathologic slides from 17 of 18 women who subsequently underwent myomectomy or hysterectomy in the follow-up period (median 8.2 months) were reviewed without knowledge of the indication for surgery or time elapsed since UAE. The presence/absence and distribution of PVA emboli, associated inflammatory response, and necrosis were noted. Necrosis of leiomyoma(s) was classified as hyaline-type, coagulative tumor cell necrosis, and/or acute suppurative necrosis.
In all cases PVA emboli were identified within smooth muscle tumors of the uterine body, its periphery, cervix, uterine body, myometrium, and/or the adnexa. A florid foreign body giant cell type of chronic inflammatory reaction was seen within 1 week of UAE and persisted with visible PVA for up to 14 months post-UAE. Typically, post-UAE leiomyomas showed hyaline-type, but rarely coagulative tumor cell necrosis and acute suppurative necrosis could be seen as well. Five of eight cases coming to surgery for complications showed necrotizing endomyometritis with tissue infarction. PVA particles are recognizable in post-UAE specimens.
Leiomyoma necrosis is typically of the hyaline type; coagulative tumor cell necrosis was rarely seen. In some cases with complications, uterine and/or cervical necrosis occurred. The applicability of these findings for UAE patients who have been successfully treated and not resected is uncertain.
Uterine leiomyoma after embolization by means of gelatin sponge particles alone: Report of a case with histopathologic features.Katsumori T, Bamba M, Kobayashi TK, Moritani S, Urabe M, Nakajima K, Mihara T, Sugihara H.
Departments of Radiology, Pathology, and Obstetrics and Gynecology, Saiseikai Shiga Hospital, Ritto, Shiga, Japan; and the Department of Pathology, Shiga University of Medical Science, Ohtsu, Shiga, Japan.
Ann Diagn Pathol 2002 Oct;6(5):307-11 Abstract quote We describe the histopathologic features of uterine leiomyoma after uterine artery embolization (UAE) in a 42-year-old woman. This patient, who was taking antiplatelet drugs for the treatment of cerebral disease, successfully underwent UAE using only gelatin sponge particles for a symptomatic uterine leiomyoma. Although menorrhagia improved moderately after the procedure, she underwent abdominal hysterectomy 11 months later because of recurrent uterine bleeding.
Histopathology revealed that most of the area of the uterine leiomyoma was characterized by extensive coagulation necrosis, which support the positive result of the procedure. No significant abnormalities were noted in either the myometrium or endometrium, which also suggested that UAE using only gelatin sponge particles is an appropriate procedure to preserve the uterus. The histologic and radiologic features of this case are discussed.
To the best of our knowledge, this is the first reported case of uterine leiomyoma after UAE using only gelatin sponge particles as a primary embolic agent.
Epithelioid May be further divided into:
Leiomyoblastoma
Clear cell
PlexiformHemorrhagic (Apoplectic) Occurs almost exclusively in young women taking oral contraceptives or are pregnant
Increased mitotic figures confined to a narrow zone adjacent to the hemorrhage
Lipoleiomyoma Contains benign lipocytes Neurilemmoma-like Myxoid Vascular
SPECIAL STAINS/
IMMUNOPEROXIDASECHARACTERIZATION Smooth muscle markers Desmin, actin Am J Surg Pathol 2001;25:253-258
Formalin-fixed and paraffin-embedded tissue sections from nine LMSs, 11 CLs, and 12 ESSs were evaluated with commercially available monoclonal antibodies against smooth muscle actin (SMA), desmin, and h-cal.
h-cal was most useful in distinguishing between CL and ESS (p = 0.01)
A significant difference between h-cal expression in LMS versus ESS was not foundOne ESS expressed both SMA and desmin but lacked h-cal expression
Conclusion:
Although the specificity of h-cal is superior to that of the others, the sensitivity of h-cal for smooth muscle differentiation was less impressive; seven LMSs and three CLs lacked h-cal expressionPropose that h-caldesmon is useful in the differentiation of cellular leiomyomata from endometrial stromal sarcomas, it is not helpful in the discrimination of leiomyosarcomas and low-grade endometrial stromal sarcomas
h-Caldesmon Expression Effectively Distinguishes Endometrial Stromal Tumors From Uterine Smooth Muscle Tumors
Marisa R. Nucci, etal.
Am J Surg Pathol 2001;25:455-463 Abstract quote
Distinction of endometrial stromal neoplasms from cellular smooth muscle tumors of the uterus is sometimes difficult. Immunohistochemistry is often not helpful because muscle actins and desmin are expressed in both neoplasms.
This study's goal was to determine whether h-caldesmon, a smooth muscle-specific isoform of a calcium, calmodulin, and actin binding protein, could effectively distinguish endometrial stromal tumors from uterine smooth muscle tumors.
The authors analyzed immunohistochemical expression in 24 endometrial stromal neoplasms (21 sarcomas and three nodules), 29 leiomyosarcomas, 32 leiomyomas (10 ``usual,'' 14 cellular leiomyoma, and eight ``highly cellular'' types), 40 myometria, and 25 endometria. h-Caldesmon was diffusely positive in all myometria, leiomyomata, and leiomyosarcomas. Of note, 16 leiomyosarcomas (55%) were positive for h-caldesmon in more than 50% of tumor cells. In five ``highly cellular'' leiomyomas, h-caldesmon expression was markedly decreased or absent in areas morphologically resembling endometrial stromal tumors, raising the possibility that these tumors may be mixed smooth muscle–endometrial stromal neoplasms. In contrast, h-caldesmon expression was absent in all endometria and endometrial stromal neoplasms apart from accompanying small vessels. Desmin was diffusely positive in all myometria and leiomyomata. The fraction of cells expressing desmin was greater than that of h-caldesmon in only 10% of leiomyosarcomas. Focal desmin expression was also present in eight of 25 (32%) endometria and 12 of 24 (50%) endometrial stromal neoplasms.
h-Caldesmon appears to be a more sensitive and specific marker of smooth muscle differentiation in the uterus than desmin and may be a useful tool for distinguishing and classifying uterine mesenchymal tumors.
HDAC8 (HISTONE DEACETYLASE 8)
- Use of Histone Deacetylase 8 (HDAC8), a New Marker of Smooth Muscle Differentiation, in the Classification of Mesenchymal Tumors of the Uterus.
de Leval L, Waltregny D, Boniver J, Young RH, Castronovo V, Oliva E.
*Department of Pathology, and the daggerMetastasis Research Laboratory, Center for Experimental Cancer Research, University of Liege, Liege, Belgium double daggerJames Homer Wright Pathology Laboratories, Massachussetts General Hospital, Harvard Medical School, Boston, MA.
Am J Surg Pathol. 2006 Mar;30(3):319-327. Abstract quote
Uterine smooth muscle tumors (SMTs) are usually recognized on the basis of their routine morphologic features; however, their distinction from endometrial stromal tumors (ESTs), the second most common mesenchymal tumor of the uterus, is sometimes problematic.
Histone deacetylases (HDACs) were originally identified as nuclear enzymes regulating histone acetylation. We have recently shown that in normal human tissues, HDAC8 is exclusively expressed in the cytoplasm of cells showing smooth muscle differentiation. In this study, we examined HDAC8 expression in SMTs and ESTs of the uterus to determine whether HDAC8 may be a useful diagnostic tool in the classification of problematic uterine mesenchymal tumors. HDAC8 immunohistochemical staining was performed in 15 leiomyomas (LMs), 9 highly cellular leiomyomas (HCLs), 8 epithelioid SMTs, 13 leiomyosarcomas (LMSs), and 17 ESTs, including 3 with sex-cord differentiation and 5 with smooth muscle differentiation. All tumors were also stained for other smooth muscle markers (desmin, h-caldesmon, smooth muscle actin [SMA], smooth muscle myosin heavy chain) and for CD10.
All LMs had moderate to strong expression of all smooth muscle markers. HDAC8 was detected in 8 of 9 HCLs and in all epithelioid SMTs (8 of 8); however, it was weak in 4 epithelioid SMTs. In contrast, desmin, h-caldesmon and smooth muscle myosin were positive in only 2 of 8, 1 of 8 and 4 of 8 epithelioid SMTs, respectively. All smooth muscle markers had similar frequency of staining in LMSs; however, HDAC8 showed overall moderate intensity compared with other smooth muscle markers, which showed stronger staining. HDAC8, h-caldesmon, and smooth muscle myosin did not stain conventional areas of ESTs or ESTs with sex-cord differentiation, whereas SMA and desmin were positive in those areas in 4 of 12 and 3 of 12 ESTs, respectively. Areas of smooth muscle differentiation in ESTs were positive for HDAC8 in all cases, but they were less constantly positive for the other smooth muscle markers. CD10 was expressed in most ESTs (14 of 17), but it was also positive in 15 of 45 SMTs.
In conclusion: 1) HDAC8 seems to be a specific marker of SM differentiation because conventional ESTs and ESTs with sex-cord differentiation are negative for HDAC8, whereas areas of smooth muscle differentiation in these tumors are consistently positive; 2) HDAC8 gives similar results to those obtained with desmin, h-caldesmon, and smooth muscle myosin in both LMs and LMSs, although the staining for HDAC8 in LMSs tends to be less intense; 3) HDAC8 may be a more sensitive marker than desmin and h-caldesmon in epithelioid SMTs. Thus, HDAC8 detection may be useful in helping the differential diagnosis of uterine mesenchymal tumors.
CD10 Utility of CD10 in Distinguishing between Endometrial Stromal Sarcoma and Uterine Smooth Muscle Tumors: An Immunohistochemical Comparison of 34 Cases
Peiguo G. Chu, etal.
Mod Pathol 2001;14:465-471 Abstract quote
Endometrial stromal sarcoma (ESS), uterine cellular leiomyoma (UCL), and uterine leiomyosarcoma (ULS) are composed mainly of spindle cells that express similar antigens such as desmin, smooth muscle actin (SMA), and muscle-specific actin (MSA). The differential diagnosis of an ESS versus a uterine smooth muscle tumor or an extrauterine spindle cell sarcoma can be problematic based solely on clinical presentation, histologic assessment, or routine immunohistochemistry.
Recently, we reported that normal endometrium, but not myometrium, as well as five cases of ESS, were positive for CD10.
We now report the results of CD10 immunohistochemistry in an additional 11 cases of ESS (total 16 cases), 10 cases of UCL, and nine cases of ULS. CD10 immunoreactivity was detected in 16 of 16 cases of ESS (100%) as compared to only 2 of 10 cases of UCL (20%) and none of nine cases of ULS (0%).
We compared the utility of CD10 immunoreactivity with that of desmin, SMA, MSA, estrogen receptor (ER), and inhibin in these tumors. Although the majority of cases of UCL and ULS were positive for SMA, MSA, and desmin, a substantial portion of cases of ESS were also positive for SMA, MSA, and desmin.
We conclude that in combination with SMA, MSA, and desmin, CD10 is a useful immunohistochemical marker in the differential diagnosis of ESS versus UCL or ULS.
Expression of CD44 standard and isoforms V3 and V6 in uterine smooth muscle tumors: A possible diagnostic tool for the diagnosis of leiomyosarcoma
Christophe Poncelet, MD
Francine Walker, MD, PhD
Patrick Madelenat, MD
Annie-France Bringuier, IA
Jean-Yves Scoazec, MD, PhD
Gérard Feldmann, MD, PhD
Emile Darai, MD, PhDHum Pathol 2001;32:1190-1196. Abstract quote
Alterations of CD44 proteins, a family of cell adhesion molecule, have been linked with tumorigenesis, carcinogenesis, and prognosis in various neoplasms.
Our aims were to evaluate and compare CD44 isoforms expression patterns in normal myometrium, uterine leiomyomas, and leiomyosarcomas and to correlate CD44 expression with clinicopathologic parameters. Fresh (n = 15) and formalin-fixed, paraffin-embedded (n = 76) tissues samples of myometrium, leiomyomas, and leiomyosarcomas were used for immunoblotting and immunohistochemistry, respectively. Semiquantitative evaluation was made after immunostaining. Monoclonal antibodies were used. By immunoblotting in myometrium and leiomyomas samples, we observed a band at 85 kd, corresponding to the apparent molecular weight of CD44s, and bands at 140 kd with the monoclonal antibodies against CD44v3 and CD44v6.
In leiomyosarcomas, CD44s and CD44v6 were detected, but not CD44v3. By immunohistochemistry, decreased CD44s expression was found in leiomyomas and leiomyosarcomas (73.9% ± 16.6% and 82.1% ± 20.7%, respectively) compared with myometrium (97.3% ± 6.2%; P < .0001). No CD44v6 staining was detected in myometrium, leiomyomas, and leiomyosarcomas. No CD44v3 expression was detected in leiomyosarcomas, whereas myometrium and leiomyomas expressed CD44v3. For the diagnosis of leiomyosarcoma, the absence of CD44v3 staining had a sensitivity, specificity, and positive and negative predictive values of 100%. In patients with recurrence of leiomyosarcomas, CD44s expression was decreased (P = .03).
We conclude that CD44s immunostaining in leiomyosarcomas may have prognostic significance. The loss of CD44v3 expression could be used as a putative diagnostic tool for uterine leiomyosarcomas.
An Immunohistochemical Analysis of Endometrial Stromal and Smooth Muscle Tumors of the gUterus: A Study of 54 Cases Emphasizing the Importance of Using a Panel Because of Overlap in Immunoreactivity for Individual Antibodies.Oliva E, Young RH, Amin MB, Clement PB.
James Homer Wright Pathology Laboratories of the Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (E.O., R.H.Y.); the Pathology Department, Emory University Hospital, Atlanta, Georgia (M.B.A.); and the Pathology Department, Vancouver General Hospital and the University of British Columbia, Vancouver, British Columbia, Canada (P.B.C.).
Am J Surg Pathol 2002 Apr;26(4):403-412 Abstract quote The expression of desmin, h-caldesmon, calponin, CD10, CD34, CD99, inhibin, and keratin (AE1/3-Cam 5.2) was studied in 10 conventional leiomyomas, 9 highly cellular leiomyomas, 9 epithelioid smooth muscle tumors, 9 leiomyosarcomas, 10 endometrial stromal tumors (4 with smooth muscle metaplasia), and 7 uterine tumors resembling ovarian sex cord tumors (UTROSCTs).
c-kit expression was tested in 10 endometrial stromal tumors, 7 UTROSCTs, and 9 leiomyosarcomas. Desmin was positive in almost all smooth muscle tumors except those of epithelioid type, which were positive in only about half of the cases. It also stained areas of smooth muscle differentiation in endometrial stromal tumors and five of seven UTROSCTs. h-caldesmon was positive in almost all nonepithelioid smooth muscle tumors and in areas of smooth muscle differentiation in endometrial stromal tumors; it was positive in only about half of the epithelioid smooth muscle tumors and negative in all UTROSCTs. Calponin was positive in most tumor types.
CD10 was positive in nine of 10 endometrial stromal tumors and five of seven UTROSCTs, although very focally in the latter group. It was also expressed, however, in almost all leiomyosarcomas, almost 50% of highly cellular leiomyomas, and rarely in the other smooth muscle tumors. CD34 was negative in the tested tumors with rare exceptions. CD99 and inhibin were positive in four of seven and one of seven UTROSCTs. Keratin positivity was found in most (five of seven) UTROSCTs and occasionally in smooth muscle tumors (seven of 37). c-kit was negative in all endometrial stromal tumors, UTROSCTs, and leiomyosarcomas.
The major conclusions of this study are as follows: 1) Pure endometrial stromal tumors are usually desmin negative. 2) In contrast to some previous studies, CD10 expression was often seen in smooth muscle tumors, including most leiomyosarcomas and almost half of highly cellular leiomyomas. As a result, a panel of CD10, h-caldesmon, and desmin should be used and will distinguish endometrial stromal tumors from highly cellular leiomyomas in most cases. 3) In contrast to a previous study, no significant differences in immunoreactivity were seen between h-caldesmon and desmin in tumors with smooth muscle differentiation. 4) The absence of h-caldesmon in UTROSCTs helps separate them from epithelioid smooth muscle tumors. 5) UTROSCTs may express epithelial, stromal, and smooth muscle markers, suggesting divergent differentiation. 6) Our study shows less frequent inhibin expression in the sex cord-like elements of the UTROSCTs than in other studies. 7) c-kit may help distinguish metastatic endometrial stromal tumors of the uterus (c-kit negative) from gastrointestinal stromal tumors (c-kit positive). 8) CD34, CD99, and keratin have no or minimal role in this area, but keratin positivity in smooth muscle tumors should not lead to their confusion with epithelial tumors.
ERYTHROPOIETIN
- Erythropoietin and erythropoietin receptor system in a large uterine myoma of a patient with myomatous erythrocytosis syndrome: Possible relationship with the pathogenesis of unusual tumor size.
Pollio F, Staibano S, Mansueto G, De Rosa G, Persico F, De Falco M, Di Lieto A.
Hum Pathol. 2005 Jan;36(1):120-7 Abstract quote.
Summary The rare condition of women with erythrocytosis and a concurrent myomatous uterus has been classified as "myomatous erythrocytosis syndrome". Substantial myoma size has been noted as a common denominator in this condition in which recent evidence have confirmed erythropoietin (Epo) production by myoma tissues themselves. Apart from its primary endocrine role in controlling erythropoiesis, Epo has been demonstrated to mediate several cellular processes such as angiogenesis, mitogenesis, and inhibition of apoptosis by autocrine and paracrine mechanisms. Recently, Epo and its receptor (Epo-R) have been shown to be involved in the growth, viability, and angiogenesis of several malignant tumors including human female reproductive organ malignancies.
In this paper, we researched on Epo and, as a first in the literature, Epo-R immunoexpression in a large uterine myoma of a term pregnant patient suffering from the myomatous erythrocytosis syndrome. Eight nongravidic leiomyomas and 8 gravidic leiomyomas were used as control group samples. Apart from confirming Epo production by myoma smooth muscle cells in the myomatous erythrocytosis syndrome, we reveal in this pathologic condition a characteristic strong Epo-R expression in myoma endothelial cells and a weak and sporadic Epo-R expression in myoma smooth muscle cells. The striking presence of Epo-R within myoma tissues in the case of the myomatous erythrocytosis syndrome allows us to speculate that myoma Epo production, besides determining erythrocytosis through systemic effects, may contribute, acting by autocrine and paracrine mechanisms, in determining the large myoma size almost always observed in this condition. Finally, we confirm a less but specific immunostaining for Epo in uterine myomas of patients without erythrocytosis and, as a first in the literature, we prove a weak and sporadic Epo-R expression in these lesions.
These last results may contribute to knowledge of the yet unclear etiopathogenesis of the most common human gynecologic neoplasm.Estrogen and progesterone receptors Positive OXYTOCIN RECEPTOR
Use of oxytocin receptor expression in distinguishing between uterine smooth muscle tumors and endometrial stromal sarcoma.
Loddenkemper C, Mechsner S, Foss HD, Dallenbach FE, Anagnostopoulos I, Ebert AD, Stein H.
Institute of Pathology, Consultation and Reference Center for Lymph Node Pathology and Haematopathology, University Hospital Benjamin Franklin, Free University, Berlin, Germany.
Am J Surg Pathol. 2003 Nov;27(11):1458-62. Abstract quote
The present study aimed to investigate oxytocin receptor (OTR) expression in the normal uterus, and particularly in uterine smooth muscle tumors and endometrial stromal sarcomas (ESSs) because these tumors can be difficult to distinguish. The expressions of OTR, CD10, h-caldesmon, calponin, smooth muscle actin, and desmin were analyzed in 10 conventional leiomyomas (LMs), 10 highly cellular leiomyomas (HCLs), eight leiomyosarcomas (LMSs), and nine ESSs.
In five normal uteri and five cases of adenomyosis, OTR was strongly expressed in the myometrium and showed expression pronounced in the surface epithelium during the late proliferative phase and at the time of ovulation, whereas the endometrial stromal cells were negative. All LMs and HCLs were strongly positive for OTR. Five cases of LMS showed moderate to strong OTR expression in 100% of the tumor cells, whereas three cases were weakly positive in 10-20% of the tumor cells. Every ESS was negative for OTR, except in regions of smooth muscle differentiation. All ESSs were positive for CD10, as were one LM, six HCLs, and five LMSs. The ESSs were negative for h-caldesmon and showed desmin positivity mainly in regions of smooth muscle metaplasia. h-Caldesmon, calponin, smooth muscle actin, and desmin were expressed in all LMs, HCLs, and LMSs except for one leiomyosarcoma with epithelioid features, which was negative for h-caldesmon and calponin.
Our study indicates that the evaluation of OTR expression is useful in the distinction of uterine smooth muscle tumors from ESSs, and that the OTR is expressed in normal and neoplastic uterine smooth muscle cells.
PROGNOSIS AND TREATMENT CHARACTERIZATION Prognostic Factors Benign Treatment Surgical removal
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