Bizarre Leiomyoma Research Articles

An Unheard Variant of Leiomyoma Cotyledonoid Dissecting Leiomyoma: Case Report

ABSTRACT Leiomyomas are benign smooth muscle tumor of the uterus with varied morphology that are well known to undergo secondary changes. A variety of other unusual patterns of uterine leiomyoma have been described, such as parasitic leiomyoma, cellular leiomyoma, symplastic or bizarre leiomyoma, epithelioid leiomyoma, intravenous leiomyomatosis, and leiomyoma with secondary changes. Some cotyledonoid dissecting leiomyoma (CDL) appears as large fungating masses with widespread extension into the broad ligament and pelvic cavity. Due to its rarity and a clinician’s lack of familiarity, such tumors are sometimes misdiagnosed as malignancies. We present a rare case report of CDL. It is a diagnostic challenge for clinicians, pathologists, and radiologists and can be confused with malignancy due to its large size. After extensive literature research, we found 28 case reports of this variant. Little is known in the literature about this entity. We present here a case report of a 65-year-old female emphasizing its clinical, radiological, gross, and microscopic findings. A total hysterectomy was performed on the patient. This tumor does not have malignant potential, but clinicians and pathologists must be aware of its existence to avoid over-treating patients as malignancy.

Raf kinase inhibitor protein expression in smooth muscle tumours of the uterus: a diagnostic marker for leiomyosarcoma?

Research questionWhat is the expression pattern of Raf kinase inhibitory protein (RKIP) in different subtypes of leiomyoma (usual type, cellular, apoplectic or haemorrhagic leiomyoma, leiomyoma with bizarre nuclei and lipoleiomyoma) and leiomyosarcoma specimens, and what is its biological role in leiomyosarcoma cells? DesignLeiomyoma and leiomyosarcoma specimens underwent immunohistochemistry staining. Leiomyosarcoma SK-LMS-1 cell line was RKIP knocked down and RKIP overexpressed, and cell viability, wound healing migration and clonogenicity assays were carried out. ResultsA higher immunohistochemical expression of RKIP was observed in bizarre leiomyomas, than in usual-type leiomyomas. Decreased expression was also found in cellular leiomyoma, with generally absent staining in leiomyosarcomas. Upon RKIP expression manipulation in SK-LMS-1 cell line, no major differences were observed in cell viability and migration capacity over time. RKIP knockout, however, resulted in a significant increase in the cell's ability to form colonies (P = 0.011). ConclusionRKIP distinct expression pattern among leiomyoma histotype and leiomyosarcoma, and its effect on leiomyosarcoma cells on colony formation, encourages further studies of RKIP in uterine smooth muscle disorders.

Atypical Leiomyoma: a rare histologic variant - A Diagnostic Challenge

Bizarre or atypical leiomyoma (LM) is defined as “leiomyoma containing giant cells with pleomorphic nuclei and little or no mitotic activity.” Due to the ominous and worrisome microscopic appearance (many large giant cells with hyperchromatic, pleomorphic, malignant looking nuclei), this variant maybe misdiagnosed as a sarcoma. It, therefore presents a diagnostic challenge to the pathologist to accurately diagnose such a tumor while ensuring that a true malignancy is not overlooked. We report a case of a atypical leiomyoma of the uterus in a 40 year old female presenting with irregular menstrual bleeding. This highlights the need for extensive tissue sampling in such dubious cases to help arrive at a correct diagnosis.Bangladesh Journal of Medical Science Vol.17(3) 2018 p.511-514

Potential diagnostic biomarkers: differential expression of LMP2/β1i and cyclin B1 in human uterine leiomyosarcoma.

Whilst most uterine smooth muscle neoplasms are benign, uterine leiomyosarcoma (Ut-LMS) is extremely malignant with a high incidence of metastasis and recurrence. Gynecological tumors are often associated with female hormone secretion, but no strong link has been detected between human Ut-LMS and the hormonal environment. In fact, the risk factors for Ut-LMS are poorly understood. In addition, no diagnostic biomarkers for differentiating between leiomyoma, a benign tumor, and malignant Ut-LMS have been found. Interestingly, mice that were homozygously deficient for LMP2/β1i were found to spontaneously develop Ut-LMS and exhibited a Ut-LMS prevalence of ~40% by 14 months of age. Thus, analyzing potential risk factors for Ut-LMS (such as LMP2/β1i) might aid the development of diagnostic biomarkers and clinical treatments for the condition. Fifty-seven patients (age range: 32-83 years) who had been diagnosed with uterine mesenchymal tumors were chosen from a pathological archive. Tissue samples from these patients were fixed in 10% buffered formalin, incubated in 4% paraformaldehyde for 8 hours, and embedded in paraffin. Tissue sections were stained with hematoxylin and eosin for standard histological examination or were subjected to further processing for immunohistochemical (IHC) examination. Serial Ut-LMS, bizarre leiomyoma, leiomyoma, and myometrium sections were subjected to IHC staining of β-smooth muscle actin, estrogen receptor, cyclin B1, LMP2/β1i, calponin h1, ki-67, tumor protein p53, and progesterone receptor. The Ut-LMS samples were positive for cyclin B1 and negative for LMP2/β1i, while the opposite result was obtained for bizarre leiomyoma, leiomyoma, and myometrium samples. The expression pattern of LMP2/β1i and cyclin B1 might be a diagnostic biomarker for human Ut-LMS. Studies of the biological roles of LMP2/β1i and/or cyclin B1 could lead to the elucidation of new targets for therapies against Ut-LMS.

MVP immunohistochemistry is a useful adjunct in distinguishing leiomyosarcoma from leiomyoma and leiomyoma with bizarre nuclei

Morphologically, distinguishing between leiomyoma (LM) and leiomyosarcoma (LMS) is not always straightforward, especially with benign variants such as bizarre leiomyoma (BLM). To identify potential markers of malignancy in uterine smooth muscle tumors, proteomic studies were performed followed by assessment of protein expression by immunohistochemistry. Archival formalin-fixed, paraffin-embedded tissues from tumors (n = 23) diagnosed as LM, BLM, and LMS (using published criteria) were selected for the study. Sequential window acquisition of all theoretical fragment ion spectra mass spectrometry was applied to pooled samples of formalin-fixed, paraffin-embedded LM and LMS tumor tissue to assay the relative protein quantities and look for expression patterns differentiating the 2 tumor types. A total of 592 proteins were quantified, and 10 proteins were differentially expressed between LM and LMS. Select proteins were chosen for evaluation by immunohistochemistry (IHC) based on antibody availability and biologic relevance in the literature. IHC was performed on a tissue microarray, and intensity was evaluated using imaging software. Major vault protein (MVP) and catechol O-methyltransferase had 3.05 and 13.94 times higher expression in LMS relative to LM by sequential window acquisition of all theoretical fragment ion spectra mass spectrometry, respectively. By IHC, MVP (clone 1014; Santa Cruz Biotechnology, Dallas, TX) was found to be 50% sensitive and 100% specific when comparing LMS to LM. Catechol O-methyltransferase (clone FL-271; Santa Cruz Biotechnology) had a sensitivity of 38% and a specificity of 88%. Six of 7 BLM had expression of MVP similar to LM. Immunohistochemical staining for MVP is a useful adjunct in distinguishing LMS from LM and BLM in difficult cases.

Can aquaporins be used as diagnostic and prognostic markers for uterine smooth muscle tumours?

ABSTRACTGenerally, uterine leiomyosarcoma is easily diagnosed. However, uterine smooth muscle tumours which show atypical histological features and unusual growth patterns may mimic malignancy and may not be easily diagnosed. In this study, our aim is to show the expressions of Aquaporin3, Aquaporin7 and Aquaporin9 in uterine smooth muscle tumours, and to investigate if aquaglyceroporins can be used as diagnostic and prognostic markers to start rapidly an appropriate treatment for patients with these tumours in order to extend the survival time. We determined that there had been 74 patients diagnosed with uterine smooth muscle tumours. We divided patients into four groups based on the diagnosis: bizarre leiomyoma, smooth muscle tumour of uncertain malignant potential, leiomyosarcoma and leiomyoma. Aquaporin3, Aquaporin7 and Aquaporin9 were detected by using monoclonal anti-Aquaporin3, anti-Aquaporin7 and anti-Aquaporin9 antibodies, respectively. In leiomyosarcoma group, we observed a statistically significant relation of Aquaporin3 expression with survival time, grade, stage, mitotic index and Ki-67 score. A significant relation of both Aquaporin7 and Aquaporin9 expressions with survival time, grade, stage was not statistically detected in leiomyosarcoma group. The decrease of Aquaporin3 expression can be used as important diagnostic and prognostic marker. Aquaporin7 and Aquaporin9 expressions cannot be used as diagnostic and prognostic markers.

Leiomyomatosis peritonealis disseminata: A case report and review of the literature.

Leiomyomatosis peritonealis disseminata (LPD) is a rare smooth muscle tumor, which is characterized by the dissemination of multiple smooth muscle-like nodules throughout the omental and peritoneal surfaces. The present report describes the case of a 33-year-old woman who had previously undergone laparoscopic myomectomy due to a bizarre leiomyoma. Five years after the initial operation, the patient was referred to our hospital with irregular episodes of right abdominal pain. As the presentation was highly suspicious of malignant uterine tumor metastasis or LPD, the patient subsequently underwent laparoscopic total hysterectomy, bilateral salpingo-oopherectomy, omental resection and excision of some of the disseminated nodules. Histological examination confirmed the diagnosis of LPD. Under laparoscopic examination, LPD must be distinguished from metastatic leiomyosarcoma and other malignant conditions. Frozen section biopsy examination may help with the diagnosis, but the final diagnosis relies on pathological examination. The etiology of LPD includes several theories, such as the hormonal, genetic and iatrogenic theories. A gonadotropin-releasing hormone agonist may be successful in shrinking the nodules. In women who have completed their families, total abdominal hysterectomy, salpingo-oophorectomy, omentectomy and debulking appears to be the optimal treatment.

Analysis of the risk factors for postoperative residue, relapse following myomectomy

To elaborate the risk factors for leiomyoma residue and relapse after different approaches of myomectomy. From Jan. 2005 to Dec. 2010 and Jan. 2011 to Jan. 2013, 769 patients underwent myomectomy were recruited in Beijing Obstetrics and Gynecology Hospital. The patients demographic, leiomyoma characteristics, preoperative gonadotropin-releasing hormone agonist (GnRH-a) therapy, surgical approach, pathological type, follow-up information were collected. Leiomyoma number was the risk factor of postoperative residue and relapse, with the leiomyoma number increased one, the risk of residue and relapse increase 1.085 times (OR = 1.085, 95% CI: 1.019-1.154, P = 0.010), 1.043 times (RR = 1.043, 95% CI: 1.014-1.073, P = 0.003) respectively. Leiomyoma type (intramural leiomyoma) was the risk factor of relapse (RR = 1.665, 95% CI: 1.029-2.693, P = 0.038). Age was not the risk factor for postoperative residue rate (P = 0.828) and relapse rate (P = 0.193). GnRH- a didn't increase the postoperative residue and relapse rate (P = 0.542, 0.133). The postoperative residue rate (P = 0.764), relapse rate (P = 0.279) between transabdominal and laparoscopic myomectomy groups had no significant difference. Bizarre leiomyoma (RR = 5.678, 95% CI: 1.373-23.490, P = 0.017) and celluar leiomyoma (RR = 2.201, 95% CI: 1.466-3.303, P < 0.01) were the risk factors for postoperative relapse rate. Leiomyoma number, leiomyoma type (intramural leiomyoma) are the main risk factors for postoperative relapse. Pretreatment of GnRH-a and laparoscopic approach wouldn't increase the rate of residue and relapse. Bizarre leiomyoma and cellular leiomyoma have a higher relapse rate than common leiomyoma.

Bizarre leiomyoma of the scrotum: A case report and review of the literature.

Bizarre leiomyomas of the scrotum are rare benign tumors that are often misdiagnosed. In this study, we present a case of bizarre leiomyoma of the scrotum in a 53-year-old male. The patient presented with a painless scrotal mass that was insidious in the right side of the scrotum with no sudden increase in size. Definitive preoperative diagnosis could not be established; however, following surgical resection of the tumor, a diagnosis of bizarre leiomyoma of the scrotum was determined by pathological examination. The patient was followed up six months following resection and no problems were reported. This is the first reported case of bizarre leiomyoma of the scrotum in China. A supplementary review of previously published cases and literature is also presented.

Prevalence of MED12 mutations in uterine and extrauterine smooth muscle tumours

To determine the prevalence of MED12 mutations in smooth muscle tumours of different organs. A total of 142 smooth muscle tumours of the uterus, gastrointestinal tract, retroperitoneum and soft tissue were analysed for MED12 mutations using Sanger sequencing. Among the uterine tumours that were examined, MED12 mutations were identified in 36 of 45 conventional leiomyomas (80%), two of six cellular leiomyomas (33%), one of four bizarre leiomyomas (25%), none of four lipoleiomyomas (0%), and two of 12 leiomyosarcomas (17%). The two MED12-mutated leiomyosarcomas were associated with benign leiomyomatous components that also harboured MED12 mutations identical to those in the respective leiomyosarcomatous components. None of the extrauterine smooth muscle tumours, including the leiomyomas, leiomyosarcomas, and angioleiomyomas, had MED12 mutations. Among uterine smooth muscle tumours, MED12 mutations are frequently present in conventional leiomyomas, but are significantly less common in histological variants of leiomyoma and leiomyosarcoma. In contrast to uterine lesions, none of the extrauterine smooth muscle tumours had MED12 mutations.

Successful pregnancy outcome after laparoscopic-assisted excision of a bizarre leiomyoma: a case report

IntroductionBizarre leiomyoma is a rare leiomyoma variant that requires a precise histopathological evaluation. Especially when diagnosed in a younger woman, this tumor leads to challenging treatment issues involving fertility preservation. Owing to the low incidence of bizarre leiomyoma, there is insufficient evidence to support myomectomy alone as an appropriate management option. Also, the impact of bizarre leiomyoma on fertility is not well known.Case presentationA 30-year-old Japanese woman who had never given birth was referred to us because of a uterine tumor with an unusual diagnostic image and was treated by a gasless laparoscopic-assisted excision with a wound retractor. Owing to an unclear margin between her uterine tumor and myometrium, a concomitant excision of adjacent myometrial tissue was required to achieve the maximum resection of her tumor. The histopathological diagnosis was bizarre leiomyoma. Seven months later, she conceived spontaneously and her pregnancy course was uneventful. At 37 weeks of gestation, an elective cesarean section was performed. Although a slight omental adhesion was noted at the postexcisional scar, her uterine wall structure was well preserved and a recurrence of bizarre leiomyoma was not noted.ConclusionsA laparoscopic-assisted excision of bizarre leiomyoma is a feasible and minimally invasive conservative measure for a woman who wishes to preserve fertility.

Use of 18F-fluorodeoxyglucose positron emission tomography for diagnosis of uterine sarcomas

We evaluated the use of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) for the diagnosis of uterine sarcomas. FDG-PET combined with serum lactate dehydrogenase (LDH) levels were compared with FDG-PET alone for the diagnosis of leiomyosarcomas (LMS), which are the most difficult uterine sarcomas to diagnose. FDG-PET imaging of endometrial cancer (EC) was used as a reference. Immunoreactivity for glucose transporter-1 (GLUT-I) correlated with FDG uptake was evaluated in sarcomas and leiomyomas (LM), including cases not examined by FDG-PET. FDG was injected after at least 5 h fasting and standardized uptake values (SUVs) were analyzed quantitatively 50-70 min after injection. Immunohistochemical expression of GLUT-1 was studied in paraffin sections of tumors using anti-GLUT-1 antibodies and GLUT-1 expression scores were derived based on staining intensities. FDG-PET was performed preoperatively in a total of 53 patients including 10 with sarcomas, 19 with EC and 24 with LM. Immunohistochemical examination was performed in 17 sarcomas, 6 EC and 9 LM [6 usual LM, 1 uterine smooth muscle tumor of uncertain malignant potential (UMP), and 2 bizarre LM (BLM)]. SUVs for uterine sarcomas and EC were significantly higher (p=0.0001) than those for LMs. There were no significant differences in SUVs among ECs, carcinosarcomas (CS) and LMS. Significant differences in SUVs existed between LM and LMS (p=0.003). However, the diagnostic accuracy for LMS was only 73%. The diagnostic accuracy of FDG-PET combined with serum LDH was 100%. GLUT-1 expression scores were significantly higher in sarcomas and EC than in LM (p<0.0001). Intermediate GLUT-1 scores were found in two of the three cases of UMP and BLM. In conclusion, FDG-PET is useful for diagnosing uterine sarcomas, while FDG-PET combined with serum LDH is useful for diagnosing LMS. Immunohistochemical examination of GLUT-1 confirmed the high FDG uptake in LMS patients.

Bizarre Leiomyoma – A Close Mimicker Of Its Malignant Counterpart: A Case Report.

INTRODUCTION: Bizarre leiomyoma is infrequently encountered in surgical pathology. It is characterized by presence of multinucleated giant cells with pleomorphic nuclei and little or no mitotic activity. CASE REPORT: A 40 year old female presented with mass per abdomen of two years duration. Clinically she was diagnosed to have fibroid and total abdominal hysterectomy was performed. Grossly uterus was bulky. Cut section revealed multiple grey-white circumscribed tumor nodules with multiple tiny cysts. Microscopy showed features of bizarre leiomyoma characterized by bizarre multinucleated giant cells, moderate to severe pleomorphism and little mitotic activity. However, coagulative necrosis was absent. CONCLUSION: Bizarre leiomyoma closely mimics leiomyosarcoma. A systematicapproach is needed to arrive at the right diagnosis and thereby exclude malignancy.

A rare symplastic or bizarre leiomyoma of the scrotum: a case report and review of the literature

BackgroundWe present a case of a symplastic or "bizarre" leiomyoma of the scrotum. Isolated cases of leiomyomas have been reported arising from the renal pelvis, bladder, spermatic cord, epididymis, prostate as well as the glans penis. However such mesenchymal lesions of the scrotum are very rare.Case presentationMacroscopically the tumour was a well-circumscribed grey-white lesion 8.5 cm in size. Because of its peculiar histological characteristics this tumour was assigned as a symplastic or bizarre leiomyoma of the scrotum.ConclusionWe present this unusual tumour and highlight some important diagnostic and treatment pitfalls related to this rare tumour. This case demonstrates that leiomyomas should be considered in the differential diagnosis of scrotal tumours.

Immunohistochemical Analysis of P16, P53, and Ki-67 Expression in Uterine Smooth Muscle Tumors

Despite well-established criteria, the distinction of uterine leiomyosarcoma from certain variants of benign leiomyoma, particularly bizarre leiomyoma, can be challenging morphologically. Recent studies reported the overexpression of p16 protein in uterine leiomyosarcoma. However, the potential role of immunohistochemistry of p16, p53, and Ki-67 in the differential diagnosis of leiomyosarcoma and bizarre leiomyoma has not been well assessed. We had immunohistochemically studied the expression of p16, p53, and Ki-67 proteins in 100 cases of uterine smooth muscle tumors, including 35 usual leiomyomas (LM), 13 cellular leiomyomas (CLM), 15 bizarre leiomyomas (BLM), 2 cases of smooth muscle tumor of uncertain malignant potential (STUMP), and 35 leiomyosarcoma (LMS). For p16 immunostain, strong and mediate-to-diffuse staining pattern (>25% cells positive) was seen in 100% of LMS and STUMP. There were 86.5% of BLM that showed positive for p16, which includes 60% of them showing mediate-to-diffuse p16 positivity. Although 38.5% of CLM and 14% of usual LM showed p16 positivity, the majority of those (70%) are focal with weak p16 staining pattern. The strong, mediate-to-diffuse p53 immunostain was seen in 91% of LMS, 60% of BLM, and 50% of STUMP, but none of usual LM and CLM. More than 10% of cells positive for Ki-67 were observed in 83% of LMS, 100% of STUMP, and 48% of BLM, but none of usual LM and CLM. Our study indicates that distinct expression patterns for p16, p53, and Ki-67 exist between leiomyosarcoma and usual LM and CLM (P<0.0001). Immunohistochemical study with a panel of antibodies to p16, p53, and Ki-67 is helpful in distinguishing LMS from CLM and usual LM. However, due to significant overlapping staining patterns between LSM and BLM (P=0.09), immunostains for p16, p53, and Ki-67 have limited role in differentiating LMS from BLM.

Clinical outcome of atypical uterine smooth muscle tumors

15028 Background: Smooth muscle tumors of uncertain malignant potential (STUMP) and atypical leiomyomas have increased mitotic activity, cellular atypia and necrosis but the degree is less than that used to define uterine leiomyosarcomas. Our objective is to evaluate the clinical outcome of patients with uterine masses histologically defined as smooth muscle tumors of uncertain malignant potential or atypical leiomyomas. Methods: A thorough search of our institution’s pathology database from 1990 to 2005 was performed. A retrospective chart review was performed to obtain initial and subsequent treatments, documented recurrences and clinical outcomes. Pathology reports and slides were reviewed and the presence of atypia, necrosis and number of mitosis was recorded. Statistical analysis was performed by Student’s T-test. Results: Eighteen patients with a histologic diagnosis of atypical leiomyoma were identified with 14 STUMP, 2 bizarre leiomyomas, 1 myxoid and 1 mitotically active leiomyoma. The mean age of these patients was 41.8 years (range: 25–77) and was significantly younger than those with leiomyosarcoma (mean age was 54 years, p &lt; 0.001). The histologic characteristics of the tumors included the presence of atypia at 50%, necrosis at 82% and mitoses at 94%. The rate of necrosis and number of mitosis was significantly less in the atypical group as compared to the leiomyosarcoma group (p values &lt; 0.05). However the rate of cellular atypia was not statistically different between the two groups. The median follow-up period was 25 months, range 1–138 months. One of the eighteen patients developed a pelvic and pulmonary recurrence at which time a low grade leiomyosarcoma was diagnosed. The recurrence occurred 32 months after the initial diagnosis of a mitotically active leiomyoma. Sixteen patients demonstrated no recurrence or metastatic disease at the time of follow-up. Conclusions: Atypical leiomyomas appear to be diagnosed in younger women which leads to challenging treatment issues involving fertility preservation. While these tumors generally behave in a benign fashion, they have histologic characteristics that may allow for progression or recurrence. Close follow-up is warranted for patients who are diagnosed with atypical leiomyomas and smooth muscle tumors of uncertain malignant potential. No significant financial relationships to disclose.

Bizarre leiomyoma of the soft tissue

Sir,Bizarre leiomyoma of soft tissue has been previously described rarely. There have been only two cases of bizarre leiomyoma reported in the nasal cavity1,2 but none at all in the nasolabial fold...

Pathologic quiz case: a 69-year-old asymptomatic man with a scrotal mass. Atypical (symplastic or bizarre) leiomyoma of the scrotum.

Pathologic quiz case: a 69-year-old asymptomatic man with a scrotal mass. Atypical (symplastic or bizarre) leiomyoma of the scrotum.

Bizarre leiomyoma: a rare form of atypical leiomyoma

Objective Selective operative hysteroscopy is today the preferred treatment for symptomatic submucous uterine fibromas. The correct pathological diagnosis is important, especially in premalignant conditions. Setting A case report is presented concerning the discrimination between bizarre leiomyoma and leiomyosarcoma in a woman with persistent menstrual periods who was treated by means of endometrial resection. Results and Conclusion Atypical leiomyomas of the uterus have been considered to be benign, but some have malignant potential and special attention is needed in such cases, especially in light of the rapid development of conservative salvage surgery.

Expression of cyclins and cyclin-dependent kinases in smooth muscle tumors of the uterus.

To investigate the cell cycle regulatory mechanisms involved in the growth of smooth muscle tumors, we studied the expression of Ki-67, cyclins E and A, and their catalytic partners, the cyclin-dependent kinases cdk2 and cdc2 by using tissue specimens from benign and malignant smooth muscle tumors. These included 20 cases of usual leiomyoma (UL), 18 of cellular leiomyoma (CL), 8 of bizarre leiomyoma (BL), 8 of uncertain malignant potential tumors (UMP) and 20 of leiomyosarcoma (LMS). The proliferation rate detected by Ki-67 was low in normal myometrium and leiomyomas (UL, CL and BL), but it was markedly increased in LMS. The expression of the cyclins (E and A) and cdks (cdk2 and cdc2) was also low in normal myometrium and leiomyomas. However, the expression of these factors was markedly increased in LMS. In addition, a survival analysis using Log-rank test, revealed that LMSs with positive staining for cyclin A and with diffusely staining for cyclin E were associated with significantly shorter survival. Our results suggest that expression of cyclins and cdks may be involved in the growth control of uterine smooth muscle tumors.