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Smooth Muscle Tumor of Uncertain Malignant Potential (STUMP) is a rare uterine tumor primarily affecting perimenopausal and postmenopausal women, typically aged between 45 and 55 years. Characterized by ambiguous histological features, STUMPs present diagnostic challenges as they cannot be definitively classified as benign or malignant based on morphology alone. This systematic review aims to elucidate the clinical, pathological, immunohistochemical, and treatment-related characteristics of STUMPs through an analysis of the literature from the past 20 years. The study follows PRISMA guidelines, utilizing comprehensive searches of PubMed and Scopus databases, yielding 32 studies that meet the inclusion criteria. From the analysis of these studies, it was revealed that the clinical presentations vary from common symptoms such as abnormal uterine bleeding and pelvic pain to incidental detection of uterine mass. Histologically, STUMPs demonstrate features overlapping with both leiomyomas and leiomyosarcomas, including mild nuclear atypia, low mitotic indices, and focal necrosis. Immunohistochemical markers such as p16 and p53 have been investigated for prognostic significance. Elevated p16 expression, often associated with aggressive behavior, was observed in a subset of STUMPs. Surgical management, typically involving hysterectomy or tumorectomy, is the primary treatment, though the extent of resection is variable. Adjuvant therapies are not routinely recommended, but long-term surveillance is advised, especially for high-risk patients. Recurrence rates for STUMPs are approximately 12%, with factors such as high mitotic counts and coagulative necrosis indicating higher risk. This review highlights the complexity of STUMP diagnosis and management, emphasizing the need for more precise diagnostic criteria and individualized treatment strategies. Understanding the morphological, immunohistochemical, and clinical behavior of STUMPs can improve patient outcomes and guide future research in this diagnostically challenging area. [ABSTRACT FROM AUTHOR]

Smooth Muscle Tumor of Uncertain Malignant Potential (STUMP) is a rare uterine tumor primarily affecting perimenopausal and postmenopausal women, typically aged between 45 and 55 years. Characterized by ambiguous histological features, STUMPs present diagnostic challenges as they cannot be definitively classified as benign or malignant based on morphology alone. This systematic review aims to elucidate the clinical, pathological, immunohistochemical, and treatment-related characteristics of STUMPs through an analysis of the literature from the past 20 years. The study follows PRISMA guidelines, utilizing comprehensive searches of PubMed and Scopus databases, yielding 32 studies that meet the inclusion criteria. From the analysis of these studies, it was revealed that the clinical presentations vary from common symptoms such as abnormal uterine bleeding and pelvic pain to incidental detection of uterine mass. Histologically, STUMPs demonstrate features overlapping with both leiomyomas and leiomyosarcomas, including mild nuclear atypia, low mitotic indices, and focal necrosis. Immunohistochemical markers such as p16 and p53 have been investigated for prognostic significance. Elevated p16 expression, often associated with aggressive behavior, was observed in a subset of STUMPs. Surgical management, typically involving hysterectomy or tumorectomy, is the primary treatment, though the extent of resection is variable. Adjuvant therapies are not routinely recommended, but long-term surveillance is advised, especially for high-risk patients. Recurrence rates for STUMPs are approximately 12%, with factors such as high mitotic counts and coagulative necrosis indicating higher risk. This review highlights the complexity of STUMP diagnosis and management, emphasizing the need for more precise diagnostic criteria and individualized treatment strategies. Understanding the morphological, immunohistochemical, and clinical behavior of STUMPs can improve patient outcomes and guide future research in this diagnostically challenging area.

Smooth muscle tumors of unknown malignant potential (STUMP) represent a group of heterogeneous uterine neoplasms showing worrisome histological features, raising concerns for a malignant behavior, but do not satisfy the diagnostic criteria for leiomyosarcoma. The existing literature remains scarce due to its rarity; therefore, there is no consensus regarding diagnostic criteria, malignant potential, treatment of choice, and follow-up. The authors report their case series to analyze the heterogeneous features of this poorly understood neoplasm. A retrospective, monocentric cohort study of all patients who underwent surgery diagnosed with STUMP at the Garibaldi-Nesima Hospital in Catania from February 2018 to August 2021 was conducted. Each patient’s age at diagnosis, symptoms, surgical treatment, tumor features, postoperative management, and follow-up were recorded. Nine STUMP cases were included. All patients reported menometrorrhagia and pelvic pain. In all women, the tumor lesion was single and intramural, and the mean diameter was 7.5 cm. Four women underwent laparotomic conservative surgery. The mean postoperative follow-up time was 36 months, and recurrences were observed in two patients. In conclusion, STUMP cases should be systematically discussed by tumor boards, pathologists with good expertise in gynecological diseases should examine the histological samples, and close surveillance is mandatory because of the possibility of recurrence or metastasis.

Smooth muscle tumors of unknown malignant potential (STUMP) represent a group of heterogeneous uterine neoplasms showing worrisome histological features, raising concerns for a malignant behavior, but do not satisfy the diagnostic criteria for leiomyosarcoma. The existing literature remains scarce due to its rarity; therefore, there is no consensus regarding diagnostic criteria, malignant potential, treatment of choice, and follow-up. The authors report their case series to analyze the heterogeneous features of this poorly understood neoplasm. A retrospective, monocentric cohort study of all patients who underwent surgery diagnosed with STUMP at the Garibaldi-Nesima Hospital in Catania from February 2018 to August 2021 was conducted. Each patient's age at diagnosis, symptoms, surgical treatment, tumor features, postoperative management, and follow-up were recorded. Nine STUMP cases were included. All patients reported menometrorrhagia and pelvic pain. In all women, the tumor lesion was single and intramural, and the mean diameter was 7.5 cm. Four women underwent laparotomic conservative surgery. The mean postoperative follow-up time was 36 months, and recurrences were observed in two patients. In conclusion, STUMP cases should be systematically discussed by tumor boards, pathologists with good expertise in gynecological diseases should examine the histological samples, and close surveillance is mandatory because of the possibility of recurrence or metastasis. [ABSTRACT FROM AUTHOR]

Objective: To correlate the ultrasound appearance of highly vascularized uterine myomas with their histopathological diagnosis.Methods: This was a prospective observational study of patients with a preoperative ultrasound diagnosis of a highly vascularized uterine myoma (color score of 3 or 4, according to the Morphological Uterus Sonographic Assessment (MUSA) criteria), characterized by circumferential and intralesional vascular pattern, who underwent myomectomy or hysterectomy. For each patient, ultrasound characteristics were recorded at baseline, including the number of lesions, the size, echogenicity and border regularity of the lesion, presence of cystic areas and shadowing within the myoma, and visualization of the endometrium. Ultrasound features were correlated with the definitive histological diagnosis. Ultrasound features were then compared between malignant and benign lesions.Results: We included 70 patients with highly vascularized uterine myomas on power/color Doppler. Their mean age was 46.5 ± 11.4 years and 13 (18.6%) were postmenopausal. At histological examination, 65 (92.9%) uterine myomas were benign lesions, comprising 32 typical leiomyomas, 29 leiomyoma variants and four adenomyomas. The remaining five (7.1%) uterine myomas were malignant masses, comprising two uterine sarcomas, one leiomyosarcoma, one neuroendocrine tumor and one uterine smooth muscle tumor of uncertain malignant potential (STUMP). The mean age of patients with a malignant lesion was significantly higher than the age of those with a benign lesion (64.8 ± 16.0 vs 42.4 ± 5.1; P < 0.001). Four out of five patients with a malignant lesion were over 45 years old. Ultrasound demonstrated cystic areas within the lesion in 10/32 (31.3%) typical leiomyomas, 16/29 (55.2%) leiomyoma variants, all four adenomyomas and in the cases of STUMP and leiomyosarcoma. Lesion borders were regular in 64/65 (98.5%) benign lesions and 2/5 (40%) malignant lesions (P < 0.05). No significant differences were observed between benign and malignant lesions with respect to echogenicity, presence of shadowing and size. The endometrium was visible in 55/65 women with benign lesions and in 2/5 with malignant lesions (P = 0.03).Conclusions: Our results showed that ultrasound features of uterine myomas, such as circumferential and intralesional vascularity, cystic areas and lesion borders, are important parameters for differential diagnosis, especially when combined with the patient's age. Such features could be useful to differentiate typical myomas from benign variants and malignant lesions in a preoperative setting and to select patients that may benefit from conservative management rather than surgery. © 2022 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Background: Benign leiomyomas (LM) and malignant leiomyosarcomas (LMS) can be distinguished by increased cellularity with mitotic activity. Uterine smooth muscle tumors of uncertain malignant potential (STUMP) are a group of rare tumors in between, for which there is still no standardized classification, nor any definitive preoperative imaging or laboratory investigations regarding the possible inclusion of STUMP in the differential diagnosis. Methods: In this study, we retrospectively reviewed 6 cases of STUMP, and assessed their pathogenesis, risk factors, and prognostic features. Results: The mean age of STUMP patients was 40.6 years old. No recurrence has been reported in all six cases after more than 3.6 years of follow-up. The mean tumor size was 9.44 cm (range 6.14–12.21). 4 cases (66.7%) with 10 mitoses per 10 high-power fields. Immunohistochemical staining for cyclin dependent kinase nhibitor 2A (p16), tumor protein p53 (p53), and Antigen KI-67 (Ki-67) was 100% positive (2/2, 6/6, and 6/6, respectively). The estrogen receptor (ER) expression rate was 50.0% (3/6), and the progesterone receptor (PR) was 33.3% (1/3). There was no correlation between the expression of these biomarkers and mitotic counts or recurrence. Conclusions: The current immunohistochemical biomarkers are ineffective in determining the probability of malignancy in STUMP patients with desire of further fertility. Detection of gene expression profiles or variants using next-generation molecular techniques may aid in disease prediction, diagnosis, treatment, and prognosis.

Uterine smooth muscle tumor of uncertain malignant potential (STUMP) is rare tumor, and regarded as sub-classification in uterine smooth muscle tumors between benign and malignant criteria. They represent a heterogeneous group of rare tumors. We report a case of a STUMP tumor in a fifty-three-year-old patient who underwent surgery for a hysterectomy. STUMP often presents with nonspecific clinical manifestation the only confirmatory examination is anatomopathological and may be supported by immunohistochemistry, hysterectomy is currently considered the gold standard of treatment. Uterine STUMP tumor represents a therapeutic dilemma. A multidisciplinary approach is mandatory. • STUMP presents a diagnostic challenge due to its nonspecific clinical presentation. • Immunohistochemical markers play a crucial role in the identification of STUMP tumors. • STUMP poses challenges in treatment decisions, underscoring the importance of a multidisciplinary approach. [ABSTRACT FROM AUTHOR]

Introduction: Smooth muscle tumor of uncertain malignant potential (STUMP) still represents a medical and surgical challenge, being rare and hard to diagnose. Normally STUMP consists in a multitude of uterine tumors that do not meet the current histologic criteria for a specific malignant or benign tumor. Clinical, imagistic and laboratory investigations seem to only raise the presumptive diagnosis in these cases, the diagnosis being confirmed during histological examination of the post hysterectomy/myomectomy specimen. Case report: We present the case of a 50-year-old female patient who was examined for the first time for pelvic pain and sensation of increased pressure in the lower abdomen in June 2020. A gynecology consultation was performed, during which a large uterine mass was felt on vaginal digital examination combined with pelvic palpation. Further pelvic ultrasound examination revealed a voluminous tumor of the left ovary. Then, a magnetic resonance imaging was performed, which showed a large pelvi-abdominal tumor of probable ovarian origin with a mixt tissue type and cystic structure, the presence of pathological abdominal and pelvic lymph nodes, ascites with a suspicion of peritoneal carcinomatosis. The patient was referred to a tertiary center and the multidisciplinary team recommended surgical treatment. A total hysterectomy with bilateral oophorectomy and stadial lymphadenectomy was performed. After surgery, the patient had a favorable evolution and was discharged five days after the intervention in a good health condition. Macroscopic and histological examinations of the biopsy pieces showed morphological aspects of uterine smooth muscles tumors with uncertain malignancy potential/STUMP and multiple uterine leiomyomas. Discussion: Due to the rarity of these tumors, the scientific literature needs to be constantly updated in order to help physicians to correctly identify and treat this pathology. It is highly recommended to identify tumors with a high malignancy potential, so that the follow up will be sufficient to discover and treat recurrences before they become life-threatening. Conclusion: Smooth muscle tumor of uncertain malignant potential remains a difficult diagnosis due to uncertainty between malignancy and benign features. Treatment approaches are difficult in these cases and must always be in accordance with the patients' desire to maintain their reproductive functions and fertility. Recurrence of STUMP has been reported, therefore a close follow up of these patients must always be performed. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate diagnostic parameters such as mitotic count and tumor size in; leiomyosarcomas (LMSs) and benign uterine smooth muscle tumors (USMTs) and to define the diagnostic value and prognostic significance of the Ki-67 proliferation index and p16, p53, and bcl-2 expressions by immunohistochemical (IHC) methods. Materials and Methods: In total, 44 cases diagnosed as LMS, atypical leiomyoma, or cellular leiomyoma at our pathology department from January 2010 to December 2015 were included. IHC staining was performed for bcl-2, p16, p53, and Ki-67 using standard techniques. Results: Tumor size and mitotic index were significant prognostic factors (p=0.008 and p=0.001, respectively). The rate of diffuse p16 expression was significantly higher in the LMS group than in the other LM group (p=0.001). A Ki-67 positivity rate of >10% (increased proliferation) was statistically significantly higher in the LMS group than in the benign USMT group (p=0.0001). No statistically significant difference was found between the LMS and benign USMT groups with respect to bcl-2 expression (p=0.892). Mitotic count and high Ki-67 expression (>%10) were statistically high in cases with relapse/ metastasis (+) (p=0.0001 and p=0.0002, respectively). Conclusion: In addition to histopathological findings (tumor size and mean mitotic count), diffuse p16 expression and p53 overexpression can be used to distinguish between benign and malignant USMTs. A high mitotic index [≥10/10 (high-power field)] and high Ki-67 expression (>10%) can serve as useful indicators for diagnosing LMS, distinguishing benign tumors, and predicting an aggressive clinical course. [ABSTRACT FROM AUTHOR]

BACKGROUND Uterine smooth muscle tumors (USMTs) constitute a group of histologic, genetic, and clinical heterogeneous tumors that include at least 6 major histologically defined tumor types: leiomyoma (ULM), mitotically active leiomyoma (MALM), cellular leiomyoma (CLM), atypical leiomyoma (ALM), uncertain malignant potential (STUMP), and leiomyosarcoma (LMS). Apart from ULM and LMS, the nature of these variants is not well defined. METHODS A total of 167 cases of different USMT variants were collected, reviewed, and diagnostically confirmed based on the World Health Organization and Stanford schemes. These included 38 cases of LMS, 18 cases of STUMP, 42 cases of ALM, 22 cases of CLM, 7 cases of MALM, and 40 cases of ULM. Molecular analysis included selected microRNAs (miRNAs), oncogenes, and tumor suppressors that are highly relevant to USMT. RESULTS Overall, 49% (17/35) of LMS cases and 7% (1/14) of STUMP cases died due to their USMT, but no deaths were attributed to ALM. miRNA profiling revealed that ALM and LMS shared similar miRNA signatures. P53 mutations and PTEN deletions were significantly higher in LMS, ALM, and STUMP compared with other USMT variants ( P < .01). In contrast, MED12 mutations were extremely common in ULM and MALM (>74%) but were significantly less common (<15%) in CLM, ALM, STUMP, and LMS ( P < .01). CONCLUSION Six types of USMT have different gene mutation fingerprints. ALM shares many molecular alterations with LMS. Our findings suggest that ALM may be a precursor lesion of LMS or have similar genetic changes during its early stage. Cancer 2014;120:3165-3177. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of uterine smooth muscle tumors depends on a combination of microscopic features. However, a small number of these tumors still pose difficult diagnostic challenges. Aim: To investigate progesterone receptor (PR) and p53 expression in leiomyomas (LMs), atypical leiomyomas (ALMs), smooth muscle tumors of uncertain malignant potential (STUMP), and leiomyosarcomas (Lass) and to evaluate the potential utility of the selected immunohistochemical markers in differentiating these tumors. Materials and methods: Immunohistochemical expression of PR and p53 was investigated in 41 uterine smooth muscle tumors comprising: 15 LMS, 4 STUMP, 6 ALM and 16 LM. Quantitative evaluation of PR and p53 expression was graded on a scale from 0 to 3+. Results: Leiomyosarcomas showed reduced PR expression. All LMs as well as ALMs and STUMP were stained intensely for PR. Conversely, LMS was strongly stained with p53, while the three non-sarcomatous groups (STUMP, ALM, LM) were either entirely negative or weakly stained for p53. Regarding both PR and p53 expression, the difference between the LMS group and the three non-sarcomatous groups was highly significant (p < 0.001). Combined high PR - low p53 expression was seen in all the 26 examined cases of the non-sarcomatous group including the STUMP cases and none of the LMS cases. Therefore, it represents a "benign" profile with 100% specificity in diagnosis of a non-sarcomatous tumor. Conclusion: Immunohistochemistry for PR and p53 is valuable as an adjunct tool to morphological assessment of problematic uterine smooth muscle tumors. [ABSTRACT FROM AUTHOR]

Uterine smooth muscle tumors (USMTs) consist of a group of histologically heterogeneous and clinically diverse diseases ranging from malignant leiomyosarcoma (LMS) to benign leiomyoma (ULM). The genetic alterations in LMS are complex, with some genetic alterations present in both LMS and other atypical histologic variants of USMT. In this study, we reviewed 119 USMTs with a diagnosis of LMS, smooth muscle tumor of uncertain malignant potential, atypical leiomyomas/leiomyoma with bizarre nuclei, and cellular leiomyoma, as well as 46 ULMs and 60 myometrial controls. We selected 17 biomarkers highly relevant to LMS in 4 tumorigenic pathways including steroid hormone receptors (estrogen receptor [ER] and progesterone receptor [PR]), cell cycle/tumor suppressor genes, AKT pathway markers, and associated oncogenes. ER and PR expression was significantly lower in LMS than smooth muscle tumor of uncertain malignant potential, atypical leiomyomas/leiomyoma with bizarre nuclei, cellular leiomyoma, and ULM (P < .01). Sixty-five percent of LMSs showed complete loss of ER, and 75% of LMSs showed complete loss of PR. All cell cycle genes were differentially expressed in different types of tumor, but significant overlap was noted. More than 75% of LMSs had Ki-67 index greater than 33%, and only 5% in all other types of USMT. Expression of the selected oncogenes varied widely among different types of USMT. PR positivity and p53 had a borderline association with progression-free survival (P = .055 for PR and P = .0847 for p53). Furthermore, high PR expression was significantly associated with a longer overall survival (P = .0163, hazard ratio 0.198). Cell proliferative indices (Ki-67) and sex steroid hormone receptors were the most valuable markers in differentiating LMS from other USMT variants., (Copyright © 2017. Published by Elsevier Inc.)

Background: Uterine smooth muscle tumor of uncertain malignant potential (STUMP) is rare tumor, and regarded as sub-classification in uterine smooth muscle tumors between benign and malignant criteria. In this study, we evaluated characteristics of cases with STUMP diagnosis in a 10-year period., Methods: We retrospectively evaluated medical records of patients with histopathological STUMP diagnosis in Istanbul Training and Research Hospital, a tertiary center. We analyzed preoperative demographic, clinical features and postoperative follow-up. Preoperative sonographic data were re-evaluated., Results: The mean age was 42 years. One patient was postmenopausal, and five patients were premenopausal. All of them had a complaint of meno-metrorrhagia. We re-evaluated preoperative sonographic images of patients, and defined 83.3% as well-defined margins, 66.7% hyperechoic, 100% heterogeneous, 66.7% non-cystic, 50% calcification and 66.7% acoustic shadowing. Pathologic features showed mean number of mitosis 8, mild atypia 66.7%, and necrosis 33.3%. In a 24-year-old unmarried female patient with myomectomy, we detected recurrance of tumor in sonographic and MRI studies after 11 months, and confirmed the diagnosis via tru-cut biopsy. There was no relevance between sonographic findings and atypia, necrosis and mitosis. The recurrence was not in relationship with mitosis, degree of atypia and necrosis. We found no relevance between tumor diameter and mitosis, atypia, necrosis and recurrence., Conclusions: STUMP is classified as an intermediate form, histopathologically so calling it benign or malignant for sure is not possible. Singulary, solidity, hyperechogenicity, heterogenecity and features of acoustic shadowing and margins can guide us to preoperative sonographic diagnosis. Recurrence/metastasis after many years from operation can be seen, and those patients should be followed long term.