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Uterine smooth muscle tumors are a heterogeneous group of mesenchymal neoplasms with multiple histologic variants and distinct biological behaviors. Pathologic classification (benign, uncertain malignant potential, malignant) relies on the evaluation of mitotic index, necrosis, and degree of cytologic atypia, with different thresholds based on each subtype. Immunohistochemistry and other ancillary studies may be necessary to establish the diagnosis in a subset of cases, given the morphologic overlap with other mesenchymal neoplasms, including low-grade and high-grade endometrial stromal tumors, inflammatory myofibroblastic tumors, and PEComa. Recent advances in molecular diagnostics have refined the classification of smooth muscle tumors, but most cases are diagnosed purely on histologic grounds., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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.

Uterine smooth muscle tumors of uncertain malignant potential (STUMPs) are rare tumors of the uterine myometrium that are often misdiagnosed, owing to limited knowledge of their characteristics on ultrasonography (US) and magnetic resonance imaging (MRI). We report a woman in her mid-30s who was hospitalized because of a pelvic tumor. A 6-cm mass was found in her lower left abdomen. US and MRI revealed a well-demarcated mass in the left adnexal area, with both cystic and solid elements, visible blood flow within the septa, a strong signal across >50% of the volume on T2-weighted imaging (T2WI), and a strong signal on diffusion-weighted imaging (DWI). After hysterectomy and bilateral salpingectomy, immunohistochemical examination confirmed STUMP. A review of the literature revealed characteristic imaging features of STUMP. Ultrasonography reveals STUMP as a solitary, well-circumscribed lesion with isoechoic or mixed echogenicity, the absence of posterior shadowing, and variations in blood flow. STUMP is characterized by strong signal intensity on T2WI, small areas of strong signal on T1WI, and non-enhancing cystic areas on contrast-enhanced MRI scans. Early diagnosis is crucial for the management and treatment of STUMP, and here we have summarized the imaging features of the lesion, thereby providing a valuable diagnostic reference., Competing Interests: Declaration of conflicting interestsThe authors declare that there is no conflict of interest.

Epstein-Barr virus-associated smooth muscle tumor (EBV-SMT) is rare in adults. The presence of intratumoral T lymphocytes and primitive rounded cells characterized this neoplasm. We report a 24-year-old Chinese man who developed EBV-SMT in the right adrenal gland with hepatitis B infection and autoimmune hemolytic anemia without a history of HIV infection, primary immune deficiency, organ transplantation, or malignant tumor. This patient had an unknown immunodeficient state. EBV-SMTs are commonly located in the liver, lung, and gastrointestinal tract but rarely in the adrenal gland. We reviewed 10 reported literature on EBV-SMT in the adrenal gland. It is imperative to distinguish EBV-SMT from conventional somatic smooth muscle tumors. The discovery of EBV-SMT forces the clinician to conduct a thorough evaluation of immune function and immune status surveillance, and these patients are vulnerable to subsequent malignant tumors., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Epstein-Barr virus (EBV) is a herpesvirus linked to nine different human tumors and lymphoproliferative disorders. Immunosuppression promotes EBV-driven malignancies. The most frequent EBV-induced malignancies are lymphomas and nasopharyngeal carcinoma. By promoting smooth muscle proliferation, EBV can induce EBV-associated smooth muscle tumors (EBV-SMT). EBV-SMT is a rare oncological entity for which no current guideline for diagnosis or management exists. Data on posttransplant EBV-SMT (PT-SMT) are scarce in kidney transplant recipients., Methods: We conducted a national multicentric retrospective study and collected cases among transplantation centers in France. Kidney transplant recipients experiencing histologically proven PT-SMT were included. We collected data on demographic characteristics of patient, history of kidney transplantation, history of PT-SMT, evolution of graft function, and patient survival., Results: Eight patients were included. The median age at PT-SMT diagnosis was 31 years (range 6.5-40). PT-SMT occurred after a median delay of 37.8 months after transplantation (range 6-175). PT-SMT management consisted in immunosuppressive regimen minimization in all patients. Introduction of mTOR inhibitors was performed in two patients. Four patients (50%) needed chemotherapy. Surgical resection was performed in four patients. At last follow-up after PT-SMT diagnosis (median 33 months (range 17-132)), five patients were considered in complete remission, and two patients had died. Two patients experienced graft rejection; two resumed dialysis (25%). All patients with available data presented with impaired graft function at last follow-up., Conclusion: PT-SMT is a subacute and progressive disease during kidney transplantation. Even if the risk of developing PT-SMT is low in kidney transplant recipients (0.07% in our cohort), PT-SMT is associated with significant graft loss, possibly due to reduced immunosuppression. Developing guidelines could help transplantation teams better manage these patients., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Research Question: What 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?, Design: Leiomyoma 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., Results: A 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)., Conclusion: RKIP 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., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The greater omentum comprises peritoneal, adipose, vascular, and lymphoid tissues. Most omental malignancies are metastatic tumors, and the incidence of primary tumors is rare. We report on a prior omental smooth muscle tumor case in an adult male patient., Case Presentation: A 54-year-old Japanese male patient with no relevant medical history was diagnosed with an abdominal mass during a routine medical checkup. Subsequent contrast-enhanced computed tomography revealed a mass of approximately 3 cm in size in the greater omentum, and a laparotomy was performed. A 27 × 25 × 20 mm raised lesion was found in the omentum. Microscopically, spindle cells were observed and arranged in whorls and fascicles. Individual tumor cells had short spindle-shaped nuclei with slightly increased chromatin and were characterized by a slightly eosinophilic, spindle-shaped cytoplasm. The mitotic count was less than 1 per 50 high-power fields. The tumor cells showed positive immunoreactivity for α smooth muscle actin, HHF35, and desmin on immunohistochemical examination. The Ki-67 labeling index using the average method was 1.76% (261/14806). No immunoreactivity was observed for any of the other tested markers. We considered leiomyoma owing to a lack of malignant findings. However, primary omental leiomyoma has rarely been reported, and it can be difficult to completely rule out the malignant potential of smooth muscle tumors in soft tissues. Our patient was decisively diagnosed with a primary omental smooth muscle tumor considering leiomyoma. Consequently, the patient did not undergo additional adjuvant therapy and was followed up. The patient was satisfied with treatment and showed neither recurrence nor metastasis at the 13-month postoperative follow-up., Discussion and Conclusion: We encountered a primary smooth muscle tumor of the greater omentum with no histological findings suggestive of malignancy in an adult male patient. However, omental smooth muscle tumors are extremely difficult to define as benign, requiring careful diagnosis. Further case reports with long-term follow-up and case series are required to determine whether a true omental benign smooth muscle tumor (leiomyoma) exists. In addition, proper interpretation of the Ki-67 labeling index should be established. This case study is a foundation for future research., (© 2024. The Author(s).)

Smooth muscle tumors that cannot be histologically classified as leiomyomas or leiomyosarcomas are defined as smooth muscle tumors of uncertain malignant potential. The location of these tumors in the nose is very rare, and the appropriate surgical extent to manage these neoplasms has not been adequately defined. Here we describe the case of a 16-year-old female adolescent who consulted due to a vascular-like tumor in the right nasal cavity who was successfully treated with intranasal surgery. The histological diagnosis was smooth muscle tumor of uncertain malignant potential. Given that these neoplasms are rare, the uncommon location in the nose, and the lack of evidence indicating the extent of surgery, it is relevant to describe and discuss this clinical case., (Sociedad Argentina de Pediatría.)

Inflammatory rhabdomyoblastic tumor is a recently introduced name for neoplasms currently included in the World Health Organization classification of soft tissue tumors under the rubric inflammatory leiomyosarcoma. Inflammatory rhabdomyoblastic tumor is an excellent example of how surgical pathologists working in conjunction with tumor biologists can greatly improve tumor classification to the benefit of patients. Over the last 28 years, understanding of this entity has undergone a fascinating evolution. This review serves as a summary of the latest findings in inflammatory rhabdomyoblastic tumor research and a diagnostic manual for the practicing surgical pathologist., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Pulmonary nodules are a common complication in solid organ transplant recipients, and may have various underlying causes, with Epstein-Barr virus-associated smooth muscle tumor (EBV-SMT) being one of them. Given the rarity of this entity, we describe the diagnosis and therapeutic interventions for post-transplant EBV-SMT in two individuals. Both cases involved female patients who were diagnosed with multiple pulmonary nodules 60 months and 116 months, respectively, after receiving living-related kidney transplantation. Pathological examination revealed a spindle cell tumor, with immunophenotype and EBV in situ hybridization supporting the diagnosis of EBV-SMT. After diagnosis, these two patients underwent intervention by decreasing their intake of immunosuppressants. As of the latest follow-up, the patients' lesion size remained stable, and their overall condition was favorable. We also reviewed literature about the morphological and molecular pathological features of EBV-SMT and highlighted the diagnosis and differential diagnosis of pulmonary spindle cell lesions especially in the setting of immunosuppression.

Benign uterine leiomyoma (U.LMA) and malignant uterine leiomyosarcoma (U.LMS), both uterine mesenchymal tumors, are distinguished by the number of cells exhibiting mitotic activity. However, uterine mesenchymal tumors contain tumor cells with various cell morphologies; therefore, making a diagnosis, including differentiating between benign and malignant tumors, is difficult. For example, cotyledonoid dissecting leiomyoma (CDL) or uterine smooth muscle tumors of uncertain malignant potential (STUMPs) are a group of uterine mesenchymal tumors for which a differential diagnosis is challenging. To date, a standardized classification system for uterine mesenchymal tumors has not yet been established. Furthermore, definitive preoperative imaging techniques or hematological examinations for the potential inclusion of CDL or STUMP in the differential diagnosis have not been defined. Several clinical studies have reported that there is no correlation between biomarker expression and mitotic rate or tumor recurrence. The immunohistochemical biomarkers reported so far cannot effectively help determine the malignant potential of CDL or STUMPs in patients who wish to become pregnant in the future. The establishment of gene expression profiles or detection of pathogenic variants by using next-generation molecular techniques can facilitate disease prediction, diagnosis, treatment, and prognosis. We examined the oncological properties of STUMP in adults using molecular pathological techniques on tissue excised from patients with uterine mesenchymal tumor. In a clinical study conducted by our medical team, the results of gene expression profiling indicated factors that may be associated with malignancy of uterine mesenchymal tumors. We herein describe the problems in diagnosing uterine mesenchymal tumors along with the results of the latest clinical studies. It is expected that the establishment of a diagnostic method targeting the characteristics of mesenchymal tumor cells will lead to the treatment of malignant tumors with a low risk of recurrence and metastasis.

Background and Objectives : The uterine smooth muscle tumors of uncertain malignant potential (STUMP) are tumors with pathological characteristics similar to leiomyosarcoma, but that do not satisfy histological criteria for leiomyoma. These are problematic lesions with intermediate morphologic features; thus, diagnosis and treatment are difficult. This narrative review aims to review data in the literature about STUMPs, particularly focusing on management and therapeutic options and strategies for women who desire to preserve fertility. Material and Methods : authors searched for "uterine smooth muscle tumor of uncertain malignant potential" in PubMed and Scopus databases, from 2000 to March 2023. Pertinent articles were obtained in full-text format and screened for additional references. Only articles in English language were included. Studies including full case description of patients with histopathological diagnosis of STUMP in accordance with Stanford criteria were included. Results : The median age was 43 years old. Symptoms are similar to those of leiomyomas, with a mean diameter of 8.0 cm. Total hysterectomy with or without bilateral salpingo-oophorectomy is the standard care for women if fertility desire is satisfied. Myomectomy alone can be considered for young patients. Although these tumors have not a high malignant potential, several studies described recurrence and metastases. Conclusions : STUMPs are complex uterine smooth muscle tumors, with a rare but reasoned clinical-diagnostic management. Considering the high clinical and histological complexity of these tumors, high level of expertise is mandatory.

Background: The term uterine smooth muscle tumor of uncertain malignant potential (STUMP) indicates a rare, equivocal entity between benign leiomyomas and leiomyosarcomas. In the present study, we evaluated a comprehensive range of clinical, surgical, and pathological features in a large multicenter series of patients with STUMP to identify risk factors for recurrence., Methods: This is a retrospective study performed by collecting consecutive cases diagnosed between January 2000 and December 2020 in five tertiary centers. Associations between STUMP recurrence and clinicopathological characteristics as well as surgical treatment modality were investigated., Results: Eighty-seven patients affected by STUMP were considered. Of them, 18 cases (20.7%) recurred: 11 as leiomyosarcoma (LMS) and 7 as STUMP. The mean time to recurrence was 79 months. We found that fragmentation/morcellation, epithelioid features, high mitotic count, Ki-67 value > 20%, progesterone receptor (PR) < 83%, and p16 diffuse expression were associated with higher risk of recurrence and shorter recurrence-free survival (RFS). Furthermore, morcellation/fragmentation and mitotic count remained independent risk factors for recurrence and shorter RFS after multivariate analysis, while the presence of epithelioid features was an independent risk factor for recurrence only., Conclusions: Our results suggest that morcellation is associated with risk of recurrence and shorter RFS, thus it should be avoided if a STUMP is suspected preoperatively. Epithelioid features, high proliferation activity, low PR expression, and diffuse p16 expression are also unfavorable prognostic factors, so patients presenting these features should be closely followed up., (© 2022. The Author(s).)

Uterine smooth muscle tumor of uncertain malignant potential is a subtype of uterine smooth muscle neoplasms. It is characterized by distinct pathologic findings with morphologic features intermediate between those of benign leiomyoma and malignant leiomyosarcoma. Clinically, STUMP is rare and its clinical picture is comparable to that of leiomyoma, with diagnosis typically being made postoperatively. Most patients with STUMP are uneventful after tumor resection. However, a small portion of patients may experience recurrence that may even lead to mortality. Given the uncommon occurrence of STUMP and the low frequency of malignant potential, currently there is still no standard guideline in treating patients with this disease and this can be challenging for physicians. Moreover, because cases are rarely available for study, investigating this tumor is difficult. Thus, matters such as the pathologic diagnostic criteria, strategy of clinical management, identification of prognostic factors, and the pathogenesis of this disease remain to be clarified. We collected and analyzed recently published case series studies of STUMP to obtain up-to-date clinical information. The current status of research in various basic and clinical aspects of this tumor was also reviewed., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2022. Published by Elsevier B.V.)

Uterine smooth muscle tumors of uncertain malignant potential (STUMP) represent a group of rare uterine smooth muscle tumors not diagnosed unequivocally as benign or malignant. To data, diagnostic criteria, malignant potential, surgical management, and follow-up of these neoplasms remain controversial. Considering that STUMP and leiomyoma are not significantly different in terms of clinical presentation and preoperative sonographic characteristics, it might be difficult to distinguish between the two affections prior to pathological confirmation at surgery. All cases should be managed by multidisciplinary tumor teams and patients' follow-up should comprise consultation with a gynecologic oncologist and a close surveillance because of the possibility of recurrence or metastasis. We present the case of a 32-year-old nulliparous woman admitted to our gynecology clinic. She was asymptomatic and only complained an increase in abdominal volume started during the past 6 months. A transabdominal and transvaginal pelvic ultrasound revealed a large heterogeneous tumor mass measuring 190×163 mm, color score 2, expanded in the left iliac fossa, suspected for benign uterine myoma. Subsequent magnetic resonance imaging confirmed a large pelvic-abdominal tumor located near the left posterior-lateral uterine wall with areas of necrosis, suggestive of subserosal leiomyoma with cystic degeneration. The patient underwent a median longitudinal laparotomy for excision of the pelvic mass. The patient was normally discharged five days after surgery in good health conditions. The final histological examination was compatible with STUMP. At present, the patient has had no relapses or metastases and she is undergoing follow-up.

Competing Interests: The authors declare no conflict of interest.

The 2020 WHO Classification defines the spindle cell, epithelioid, and myxoid variants as subtypes of uterine leiomyosarcomas (LMS). Presence of cellular atypia (size variation of polymorphic nuclei > 2-3:1), tumor cell necroses, and mitotic count (usually ≥ 10 MF/10 HPF) are still the key features for diagnostic separation from uterine leiomyomas. Preanalytic variables, staining quality, as well as intralesional geographic distribution may affect the mitotic count. Smooth muscle tumors of uncertain malignant potential (STUMP) still exist as a not yet well-characterized diagnostic entity. Immunohistochemical stains against p16, p53, Ki-67, and WT‑1 may aid differential diagnosis in selected cases. Diagnostic molecular pathology is not yet relevant for diagnosis., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Fumarate hydratase-deficient leiomyomas (dFH leiomyomas) often display atypical pathologic features yet exhibit a benign clinical course. Recent data suggest that dFH leiomyomas may be misclassified as smooth muscle tumors of uncertain malignant potential, a category that encompasses a heterogenous subgroup of uterine neoplasms with smooth muscle differentiation and atypical features that impart ambiguity regarding their expected clinical behavior. dFH leiomyomas can be seen in the context of hereditary leiomyomatosis and renal cell carcinoma syndrome or in the sporadic setting. In this retrospective study, we sought to examine the prevalence and clinicopathologic characteristics of dFH leiomyomas in 48 tumors previously diagnosed as smooth muscle tumors of uncertain malignant potential from 38 patients. Of these 48 tumors, 3 (6.3%) occurring in 2 patients were found to be deficient for FH by immunohistochemistry, including 1 uterine and 2 extrauterine (abdominopelvic) tumors. The 3 tumors showed histologic features typical of dFH leiomyomas, including hemangiopericytoma-like vessels, edema, macronucleoli, and atypia. Neither patient developed recurrent leiomyomas or renal cell carcinoma, and both were alive without disease at last follow-up. Our data suggest that dFH leiomyomas should be considered in the differential diagnosis of smooth muscle tumors of uncertain malignant potential, even in the context of extrauterine disease. Identification of FH deficiency in these tumors supports their classification as dFH leiomyomas despite their atypical morphologic features and/or clinical presentation. Importantly, detection of dFH in these cases may identify women at increased risk for hereditary leiomyomatosis and renal cell carcinoma who would benefit from genetic counseling and consideration for FH germline testing., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 by the International Society of Gynecological Pathologists.)

Epithelioid leiomyosarcoma of the uterus is rare and poorly understood. Herein, we characterize a large institutional series of epithelioid leiomyosarcomas aiming to define outcome-determinant diagnostic pathologic features. We also retrieved epithelioid smooth muscle tumors of unknown malignant potential and evaluated a consecutive cohort of leiomyomas for epithelioid subtypes. Of a total of 1177 uterine leiomyosarcomas, 81 (7%) were categorized as epithelioid after review. Epithelioid leiomyosarcoma was strictly defined as having round to polygonal cells with visible pink cytoplasm and round to ovoid nuclei in ≥50% of the tumor volume. Average age was 55 years (range: 26 to 81 y). Median tumor size was 11 cm; tumor was >5 cm in 93% of subjects; 47% were stage 1 at presentation. An infiltrative tumor border was observed, grossly and/or microscopically, in 89% of cases; necrosis was noted in 80%, and vascular invasion in 47%. Mitotic count in 2.4 mm2 (totalling 10 high-power fields, each field 0.55 mm in diameter) ranged from 3 to 100 (median: 26). All cases had moderate, severe or highly pleomorphic atypia. All cases had 2 or 3 of the following: necrosis, at least moderate atypia and ≥4 mitoses in 2.4 mm2. Immunohistochemistry revealed frequent expression of smooth muscle markers including SMA (96%), desmin (95%), and caldesmon (81%). HMB45 and Melan-A were negative in 92% and 100% of cases, respectively. Estrogen and progesterone receptors were expressed by 65% and 54% of tumors, respectively. Follow-up information was available in 68 subjects (median: 23 mo, range: 1 to 254); cancer-related death occurred in 63%, and an additional 15% had recurrent or metastatic disease at last follow-up. Disease-specific survival was shorter in epithelioid leiomyosarcoma patients (median: 44  mo; 35% at 5-y) than in a matched cohort of nonepithelioid leiomyosarcoma (median: 55 mo; 46% at 5-y) (P=0.03). Three epithelioid smooth muscle tumors of unknown malignant potential were evaluated, all <5 cm in size and with atypia and/or irregular borders but mitotic count below the threshold for malignancy. Two of these had follow-up available, which was uneventful. Of 142 consecutive leiomyomas assessed, none had epithelioid morphology as defined. Epithelioid leiomyosarcoma is an aggressive neoplasm, sometimes with a remarkably low mitotic count. In the setting of an epithelioid smooth muscle tumor of the uterus, we postulate that the diagnosis of malignancy is made in the presence of ≥2 of the following: moderate or severe atypia, ≥4 mitoses/2.4 mm2 and tumor cell necrosis. In their absence, the finding of tumor size ≥5 cm, vascular invasion, infiltrative edges or atypical mitoses should be treated with caution, and designation as of at least uncertain malignant potential is warranted., Competing Interests: Conflicts of Interest and Source of Funding: D.B.C. work is supported by the Ovarian Cancer Research Alliance (Ann Schreiber Mentored Investigator Award; grant number 650320). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Canine smooth muscle tumors (SMTs) commonly develop in the alimentary and female genital tracts and less frequently in soft tissue. The definition of histological criteria of malignancy is less detailed for SMTs in dogs than in humans. This study evaluated the clinicopathologic features of canine SMTs and compared the veterinary and human medical criteria of malignancy. A total of 105 canine SMTs were evaluated histologically and classified according to both veterinary and human criteria. The Ki67 labeling index was assessed in all SMTs. Estrogen receptor (ER) and progesterone receptor (PR) expression was evaluated for soft tissue SMTs. Follow-up data were available in 25 cases. SMTs were diagnosed in the female genital tract (42%), alimentary tract (22%), and soft tissue (20%). Soft tissue SMTs frequently arose in the perigenital area, pelvic cavity, and retroperitoneum. A subset of soft tissue SMTs expressed ER and/or PR, resembling the gynecologic type of soft tissue SMT in humans. SMTs were less frequently malignant when assessed with human criteria than with veterinary criteria, better reflecting their benign behavior, especially in the genital tract where human criteria tolerate a higher mitotic count for leiomyoma. Decreased differentiation was correlated with increased proliferation, necrosis, and reduced desmin expression. Mitotic count, Ki67 labeling index, and necrosis were correlated with metastases and tumor-related death. Further prognostic studies are warranted to confirm the better performance of the human criteria when assessing SMT malignancy, especially genital cases, to confirm their usefulness in ER/PR-expressing soft tissue SMTs, and to better define the most useful prognostic parameters for canine SMTs.

Introduction: Immunodeficient patients, including the recipients of solid organs, exhibit an increase in the incidence of neoplasms. Post-transplant smooth muscle tumor (PTSMT) is a distinct and infrequent entity of these groups of neoplasms. Epstein-Barr virus (EBV) is considered to be involved in the etiology of this neoplasm., Case Report: A 28-year-old man who underwent liver transplantation presented with abdominal pain and diarrhea for several months. He had a history of resistant systemic cytomegalovirus (CMV) infection after transplantation. Radiologic evaluation and colonoscopy revealed multiple liver, spleen, lung, and colon lesions. Microscopic assessment of colon and liver lesions using IHC study were in favor of spindle cell proliferation with mild atypia and a mild increase in mitotic rate without any necrosis, with features of smooth muscle tumor. Considering the transplantation history, EBER chromogenic in situ hybridization (CISH) study on paraffin blocks was requested, which demonstrated EBV RNA in tumor cell nuclei, suggesting EBV-associated smooth muscle tumor. In addition, PCR for CMV on paraffin blocks was positive. PCR for EBV and CMV viremia were negative. The dosage of immunosuppressive agents was reduced, and currently, he is being followed, with slow expansion in the size of the lesions., Conclusion: Although the incidence of post-transplant smooth muscle tumors (PTSMTs) is low, it should be remained in the differential diagnosis in post-transplantation patients, especially dealing with multifocal tumors. As strong stimulant for smooth muscle tumors, close follow-up and screening for EBV and CMV infection and early treatment at the time of diagnosis are recommended to avoid these virus-induced tumors., (© 2021. The Author(s).)

Uterine smooth muscle tumors are the most common tumors of the female genital tract and include leiomyoma (LM) and its variants, smooth muscle tumors of uncertain malignant potential (STUMP), and leiomyosarcoma (LMS). Accurate diagnosis of LMS is determined by nuclear atypia, mitotic count, and the presence or absence of tumor cell necrosis, a process which is often difficult and subjective. In this study, we correlated digital quantification of proliferation marker Ki-67 and mitotic marker phosphohistone H3 (PHH3) to mitotic count, classification of uterine smooth muscle tumors, and clinical outcomes. A total of 39 cases (17 LMS, 5 STUMP, 10 LM with bizarre nuclei, and 7 LM) were included. Mitotic count, Ki-67, and PHH3 were significantly correlated. When comparing the LMS group to the STUMP, LM with bizarre nuclei, and LM groups combined, LMS showed a significantly greater digital quantification of Ki-67 (median 10.6% vs. 0.4%, P<0.001) and PHH3 (median 0.5% vs. 0.14%, P=0.022). Ki-67 was a better predictor of LMS compared with PHH3 (area under the curve 0.92 vs. 0.73, P=0.017). Above a threshold Ki-67 value of 3.8%, the sensitivity was 82% and specificity was 91%. Clinical outcomes were available for 10 patients (8 LMS and 2 STUMP), and inferior progression-free survival was noted for patients with higher Ki-67 values. Overall, this study suggests that digital quantification of Ki-67 can potentially aid in diagnosis of LMS., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 by the International Society of Gynecological Pathologists.)

Objective: Uterine smooth muscle tumors of uncertain malignant potential (STUMP) is a heterogeneous group of tumors with histological and biological diversity that cannot be defined as a benign leiomyoma or malignant leiomyosarcoma. The study aims to investigate the diagnostic methods, treatment management and prognosis of STUMP patients in a 13-year period., Study Design: We retrospectively reviewed the clinicopathologic information of 31 STUMP patients in Peking University People's Hospital. Statistical analyses were conducted to compare the difference of clinical characteristics between the women in myomectomy group and those in hysterectomy group., Results: The most common clinical presentation was menstrual disorder. The tumors were mainly manifested as hypoechoic, non-cystic nodules with low blood flow signal by pelvic doppler ultrasonography. Most tumors carried Ki-67 index ranging from 10% to 30%. Immunohistochemical markers such as ER, PR, p16 and Desmin was positively expressed in tumors. At the first operation, 21 cases underwent myomectomy and 10 cases underwent hysterectomy. The patients in myomectomy group were younger than those in hysterectomy group. In the follow-up period, two cases experienced a relapse in the form of STUMP within 36 months. One case died of cardiovascular accident while the other cases were alive. Six of 21 women in myomectomy group desired pregnancy and two healthy live births were recorded., Conclusion: The diagnosis of STUMP primarily depends on histopathologic features. Fertility-sparing surgery may be a treatment selection for patients with fertility desire. Patients with STUMP, especially in the case of myomectomy, should be informed of recurrence risk and monitored closely., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier B.V.)

Frozen sections of uterine smooth muscle tumors are infrequently required, and related diagnostic difficulties are seldom discussed. We analyzed the clinicopathologic features of 112 frozen sections of uterine smooth muscle tumors and determined the accuracy, reasons for deferrals, and causes of interpretational errors. Most patients (median age, 45 y) presented with pelvic mass symptoms (53%). The main reasons for a frozen section examination were an abnormal gross appearance including loss of the usual whorled pattern of leiomyoma (36 cases, 32.1%), and intraoperative discovery of an abnormal growth pattern and extrauterine extension of a uterine tumor (28 cases, 25%). There were 9 leiomyosarcomas and 103 leiomyomas, including 18 benign histologic variants. An accurate diagnosis of malignancy was achieved in all leiomyosarcomas, with the exception of a myxoid leiomyosarcoma. In 99 cases (88%), the frozen section diagnosis concurred with the permanent section diagnosis (false positives, 0.9%; false negatives, 0%). Misinterpretation of stromal hyalinization as tumor cell necrosis in a leiomyoma with amianthoid-like fibers was a major discrepancy. Two minor discrepancies did not lead to a change in management. The diagnosis was deferred in 10 cases (8.9%) because of stromal alterations, unusual cellular morphology, uncertain type of necrosis, and abnormal growth patterns. Thus, although various stromal and cellular alterations can cause diagnostic uncertainty, leading to deferrals, frozen section diagnosis of uterine smooth muscle tumors has a high accuracy rate. While a definitive frozen section diagnosis of malignancy may be made when there is unequivocal atypia, indisputable mitotic figures, and tumor cell necrosis, it is important to remember that nonmyogenic mesenchymal tumors may also mimic uterine smooth muscle tumors. In a frozen section setting, it would be sufficient to issue a diagnosis of "malignant mesenchymal tumor." For tumors that do not meet the criteria for malignancy, issuing a frozen section diagnosis of "atypical mesenchymal tumor and defer the histologic subtyping to the permanent sections" is appropriate., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

A girl, aged 7 years, was admitted due to pain in both lower limbs for more than one year. Lumbar MRI showed soft tissue masses in the paravertebral region. Cerebral MRI showed nodular masses in the cavernous sinus at both sides. Chest CT showed high-density nodules in the outer basal segment of the right inferior lobe and the anterior segment of the left upper lobe of the lung. Biopsy of lumbar lesions showed Epstein-Barr (EB) virus-related smooth muscle tumor. Genetic testing showed a de novo mutation, c.725&#95;730delAGAGTA (p.K242&#95;S243del), in the ITK gene. The masses in the lumbar vertebra were removed by surgery, and then the pain in both lower limbs disappeared. This article reports a case of EB virus-related smooth muscle tumor with a deletion mutation in the ITK gene, which provides experience for the diagnosis and treatment of this disease.

The diagnosis of uterine smooth muscle tumors is sometimes difficult, as these tumors may show worrisome features, suspicious for but not diagnostic of malignancy. The recommended immunohistochemical panel in this setting is currently under debate. In this study, we aimed to find a panel of immunohistochemical stains that would be helpful in determining the correct diagnosis in ambiguous uterine smooth muscle tumors, with an emphasis on investigating the possible usefulness of the WT1 antibody. Uterine leiomyomas were found to be immunoreactive with WT1. Since a previous study reported on the lack of immunoreactivity of uterine leiomyosarcomas with WT1, we speculated that WT1 might be useful in this setting. We retrospectively reviewed the medical charts and slides of 91 patients: 22 with leiomyosarcoma, 15 with smooth muscle tumor of uncertain malignant potential, and 54 with leiomyoma. Immunohistochemical stains for WT1, p16, p53, and Ki67 were performed on each case. We found that immunoreactivity with p16 and Ki67 (>40% and >10% of the tumor cells, respectively) and loss of nuclear expression of WT1 (<10% of the tumor cells) were significantly more common in leiomyosarcomas (all P<0.001). Mutated p53 immunohistochemical staining pattern was significantly more prevalent in leiomyosarcomas than in leiomyomas (P<0.001). Thus, in diagnostically challenging uterine smooth muscle tumors, we recommend using an immunohistochemical panel composed of Ki67, p16, p53, and WT1. A positive result in either of the former 2 (p16 >40% and/or Ki67 >10%) has the strongest association with leiomyosarcoma (sensitivity: 95.5%, specificity=88.9%, positive predictive value=77.8%, negative predictive value=98.0%)., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 by the International Society of Gynecological Pathologists.)

Objective: To evaluate the clinical outcomes, histopathological features, and obstetric and oncological outcomes of uterine smooth muscle tumor of uncertain malignant potential (STUMP)., Methods: We conducted a single-center, database review of patients with STUMP between January 2001 and December 2015. We investigated the clinical, operative, histopathologic, recurrence, and fertility outcomes of the included cases., Results: Nineteen patients with STUMP were studied. Three were reclassified as sarcoma after slide review, and 16 patients were finally included in the study. The mean age was 45 years. Ki-67 expression was ≥10% in 25.0% of cases and 30% in the only recurrent case. Recurrence occurred 52 months after a diagnosis of STUMP in a 56-year-old female patient who underwent hysterectomy. Two of six patients who underwent myomectomy had fertility requirements, and both successfully delivered babies without recurrence. Recurrence was not related to mitosis, degree of atypia, or necrosis. There was also no relationship between type of surgery or surgical approach and recurrence., Conclusions: Patients with STUMP warrant a pathological review process in centers with experience. Fertility-preservation is worth attempting, but young patients must be followed-up closely. Ki-67 might be a valuable marker predicting recurrence.

Uterine leiomyoma and leiomyosarcoma are located at the ends of the spectrum of smooth muscle lesions. Leiomyosarcoma belongs to the complex genomic sarcomas characterized by complex karyotypes. In contrast, leiomyoma, has a low level of chromosomal complexity. The analysis of genomic profiles of uterine smooth muscle tumors shows that genomic complexity, which is an expression of chromosomal instability, correlates with the metastatic potential and malignity of tumors: the more genetically complex a smooth muscle tumor is, the more malignant is its progression. In uterine tumors with uncertain malignant potential, the assessment of genomic index by CGH array, that is, counting the genomic complexity of a tumor, allows tumors with a risk of recurrence such as leiomyosarcomas to be distinguished from benign tumors like leiomyomas. The prognosis of leiomyosarcoma is poor and the most powerful prognostic factor so far is stage, as the histologic grade is not informative. In the quest to find efficient molecular prognostic factors, the transcriptomic signature CINSARC Nanocind, a mirror of chromosomic complexity and instability, outperforms stage, in both overall and recurrence-free survival. Genomic index and the CINSARC signature will contribute to improving diagnoses, therapeutic strategies, and randomization in future clinical trials. The biological understanding of the links between the CINSARC signature and metastatic mechanisms may lead to the development of new drugs. Furthermore, ctDNA is a promising new technique to detect residual disease and early recurrence., (© 2020 Wiley Periodicals LLC.)

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is an autosomal dominant familial syndrome that results from germline mutation in the fumarate hydratase (FH) gene and is associated with an increased risk for smooth muscle tumors of the uterus and skin and renal cell carcinoma. HLRCC associated RCC develop in up to 25% of patients, often presenting in the fourth decade and are high stage, aggressive tumors with poor clinical outcome. Most women with HLRCC develop large and bulky uterine smooth muscle tumors (USMT) in the second to third decade, thus presenting the ideal opportunity for early detection of HLCC to enable timely implementation of surveillance for their RCC risk. However, the concept of screening women with USMT for HLRCC is challenging given that HLRCC is rare but USMT are common. In addition, FH deficiency in USMT can also result from sporadic FH gene aberrations, unrelated to HLRCC, further complicating any potential screening process. Recent studies show that tumor morphology can be used to identify FH deficiency in USMT and thereby direct patients to formal genetic counseling. The low magnification clues of staghorn shaped blood vessels and alveolar pattern should prompt for high magnification examination for eosinophilic cytoplasmic inclusions and oval nuclei containing prominent eosinophilic macronucleoli surrounded by a halo. Additional clues include Schwannoma-like growth and chain-like distribution of the tumor cells. Although immunostains exist for FH and 2SC, their role is limited in the presence of well-developed FH deficient morphology. The prevalence of germline pathogenic mutation in FH among women with USMT with FH deficient morphology is as high as 50% in some studies, with somatic FH mutation accounting for the remainder. Therefore, morphologic evaluation of USMT for features of FH deficiency can serve as a screening tool for HLRCC syndrome by triaging patients to formal hereditary risk assessment., (© 2020 Wiley Periodicals LLC.)

Tumors of the perivascular epithelioid cells (PEComa) of the uterus are rare mesenchymal tumors that are characterized by the expression of both melanocyte and smooth muscle markers. It is often difficult to distinguish PEComas from other uterine tumors: endometrial stromal sarcoma, smooth muscle tumors including epithelioid tumors, melanoma and clear cell sarcoma. We report two cases of malignant PEComas of the uterus, treated in two different hospitals, found in women over 60, presenting a clinical picture of metrorrhagia in a context of myomatous uterus. In the first case, the histological examination of the hysterectomy specimen found a diffuse proliferation of epithelioid cells expressing HMB45. In the second case, the question of the differential diagnosis of the PEComa with a uterine epithelioid leiomyosarcoma arose, in front of the weak or even absent expression of the melanocytic immunohistochemical markers (melanA negative and focal HMB 45). The opinion requested from a network of experts (RRePS) had made it possible to validate the diagnosis of PEComa, notably by carrying out a complement of immunohistochemistry (expression of cathepsin K) by the tumor cells. In spite of its rarity, the diagnosis of PEComa should be considered before this type of epithelioid or clear cell uterine tumor because of the possibility of treatment by targeted therapies such as the mTOR (mammalian target of rapamycin) inhibitors., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Uterine leiomyoma represents the most common pelvic tumor in females, including numerous histological subtypes, from which smooth muscle tumors of uncertain malignancy potential (STUMP) represents the diagnostic challenge. On the other hand, the study of the relapse risk markers after laparoscopic myomectomy is of high interest. We investigated the molecular phenotype of different types of leiomyoma after hysterectomy or laparoscopic surgery in reproductive and menopausal women. Standard immunohistochemistry was used to detect proliferation markers Ki67 and cyclin D1, apoptotic markers Bcl2 and Cas3, and ER and PR. The results of our study indicated that ER expression is significantly higher in relapsed leiomyoma, compared to control group. In addition, relapsed leiomyomas are characterised with high proliferation and apoptotic index. With regard to STUMP despite histological homogeneity, this entity is characterised with the presence of three distinct molecular subtypes, based on proliferation and apoptotic marker expression, which should be used as diagnostic aid in these tumors.

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Perivascular epithelioid cell tumors (PEComa) are rare neoplasms characterized by co-expression of melanocytic and muscle markers. HMB45 and Melan-A are used to confirm a PEComa diagnosis; however, both are often focally expressed and sensitivity for Melan-A is low. PNL2 is a reliable biomarker for epithelioid melanoma and renal angiomyolipoma/PEComa. The objective of this study was to determine PNL2 utility in diagnosing uterine PEComas as well as distinguishing PEComas from uterine smooth muscle tumors (SMTs). Twenty-one uterine PEComas and 45 SMTs were analyzed for PNL2; a subset was also stained for HMB45, Melan-A, Cathepsin-K, Desmin, and h-Caldesmon. Cases were scored as negative (0), focal (<10% of tumor cells), or patchy to diffusely positive (>10% of tumor cells). PEComas were positive for PNL2, HMB45, and Melan-A in 86%, 100%, and 57% of cases, respectively. In PEComas, PNL2 was patchy to diffusely positive more frequently (10/18, 56%) than Melan-A (4/12, 33%). In contrast, 2 of 45 (4%) SMTs were focally PNL2 positive; HMB45 was focally positive in 4 SMTs (11%) and all were negative for Melan-A. Desmin and h-Caldesmon were positive in 90% and 57% of PEComas, and 91% and 82% of SMTs. Cathepsin-K was positive in 100% of PEComas and 93% of SMTs. PNL2 is a useful biomarker for the diagnosis of uterine PEComa, with comparable sensitivity and specificity to HMB45. In contrast, PNL2 stains more PEComas when compared with Melan-A. Cathepsin-K, Desmin, and h-Caldesmon are of little utility for distinguishing PEComas and SMTs; however, lack of Cathepsin-K argues against PEComa. These results suggest that PNL2 should be used in conjunction with HMB45 in the diagnosis of PEComa of the uterine corpus.

Our objective was to evaluate the diagnostic utility of 2 new proliferation markers, cyclin D1 and minichromosome maintenance complex component 2 (MCM2), in comparison with p16, p53, and Ki67 in differentiating the spectrum of smooth muscle tumors. An institutional database search from 2009 to 2017 identified 10 cases of uterine leiomyoma with bizarre nuclei (LBN), 12 smooth muscle tumors of uncertain malignant potential, and 13 leiomyosarcomas (LMS). Ten resected leiomyomas (LM) were included as controls. Immunohistochemistry was performed on the befitting representative block from each case. Ki67 was <10% in all LMs and LBNs, whereas >10% in all LMSs. Although wild-type in majority of cases, p53 was overexpressed in 38% of LMSs. Cyclin D1 nuclear positivity in LMs, LBNs, and smooth muscle tumors of uncertain malignant potentials ranged from 0% to 65% of neoplastic cells with mostly weak to moderate staining intensity. Instead, cyclin D1 expression was <5% in all LMSs. The ratio of MCM2 positivity exhibited a similar wide range (<1%-80%) in LMs, LBNs, and smooth muscle tumors of uncertain malignant potentials but interestingly, 92% (12/13) of LMSs were diffusely and strongly positive for MCM2 (>80% cell positivity). Overall, for diagnosis of LMS, the sensitivity for diffuse intense MCM2 staining was higher (92%) compared with diffuse staining for p16 (77%); however, specificity of MCM2 and p16 was comparable (94% and 97%, respectively). Herein, we describe the immunohistochemical profile of 2 new proliferation markers, cyclin D1 and MCM2 in uterine smooth muscle tumors. A combination of diffuse strong MCM2 and p16 reactivity with increased Ki67 index can reliably distinguish LMSs from benign histologic mimics.

Introduction: Epstein-Barr virus (EBV) associated smooth muscle tumors (SMTs) usually present under the condition of immunosuppression, including congenital immunodeficiency syndrome-SMT, post-transplantation-SMT and HIV-SMT. HIV-SMTs are most likely to invade the central nervous system, followed by the liver, lungs, and other locations. Many laboratory techniques, including serological techniques, polymerase chain reaction and immunohistochemistry (IHC), are employed to determine the aetiologies of these tumours. With respect to therapy, surgical resection is the main treatment. In patients with immunodeficiency, improving immune status is significant for defending against other viruses. We describe a case of the primary focus of SMT in the liver of HIV-positive patient without any metastasis., Patient Concerns: A young male HIV-positive patient complained of fever and abdominal pain for 2 months., Diagnosis: IHC of liver tissue confirmed the finding: EBV-related smooth muscle tumor., Interventions: Given the patient's general condition, he was not a suitable candidate for surgical resection. He was given antibiotics, antifungal agents and EBV-directed agents to control infection as well as highly active antiretroviral therapy to enhance the immunity., Outcomes: The patient's symptoms improved. He was discharged., Conclusions: In conclusion, EBV-related HIV-SMTs is a rare neoplasm found in the liver among immunodeficient patients. This case highlights that a variety of examinations such as IHC for smooth muscle markers (smooth muscle actin and desmin) and EBER, as well as polymerase chain reaction for EBV DNA should be done when diagnoses are ambiguous.

Objective: To investigate the clinical outcomes and histopathological features of uterine smooth muscle tumors of uncertain malignant potential (STUMP)., Methods: The study analysed cases diagnosed with uterine STUMP in a tertiary center, between January 2003 and September 2018. We investigated the clinical, operative and histopatholologic data of the cases. Follow-up information and clinical outcomes were also examined., Results: 28 cases with uterine STUMP were studied. The mean age of the patients was 44.5 ± 9.0 years and the median parity was 2 (0-6). The mean tumor diameter was 6.3 cm (range 2-27 cm) and most (78.6%) of the tumors were located intramurally. In 25% of the cases diagnosis was after myomectomy, while in the others diagnosis was after hysterectomy. Of the patients who wanted to preserve the uterus and their fertility and who did not therefore undergo a subsequent hysterectomy, one patient became pregnant without any complication. One case with a history of myomectomy, presented as STUMP. The median follow-up time was 45.4 months (range 5-180). Recurrence occured in one case (3.7%) 33 months after diagnosis. Distant metastasis occurred in the lungs and the pathology of the biopsy was liposarcoma, and the patient died of the disease 62 months after diagnosis., Conclusion: Uterine STUMP is a rare condition, and diagnosis can be difficult, often with unusual combinations of findings. Prognosis for the patient is unclear and their is a risk of recurrence with the tumors. To reduce mortality, regular follow-up and a centralised approach are recommended., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Smooth muscle tumors are the most common mesenchymal tumors of the female genital tract. However, awareness of tumor variants and unconventional growth patterns is critical for appropriate classification and patient management. For example, recognition of fumarate hydratase-deficient leiomyomas allows pathologists to alert providers to the potential for hereditary leiomyomatosis and renal cell carcinoma. Furthermore, myxoid and epithelioid smooth muscle tumors have different thresholds for malignancy than spindled tumors and should be classified by criteria specific to these variants. This article provides an overview of smooth muscle tumors of each major organ of the gynecologic tract and discusses diagnostic challenges., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Recipients of solid organ transplants are prone to various complications that are seldom encountered in immunocompetent individuals. Post-transplant lymphoproliferative disorder (PTLD) is the best known and commonest Epstein-Barr Virus (EBV)-associated malignancy post solid organ transplant. EBV-associated smooth muscle tumors (EBV-SMT) including leiomyomas and leiomyosarcomas are rare and much less studied than PTLD. We recently encountered two cases of EBV-SMT post lung transplantation and here we summarize their clinical features and course together with a literature review., Method: Clinical data and treatment details of two patients who developed EBV-SMT were reviewed and retrieved up to December 31, 2017. English literature was searched through the PubMed database from 1965 to 2017 for studies of the association between lung transplant and EBV-SMT., Results: The incidence of PTLD is higher among lung transplant recipients compared to kidney transplant recipients, an observation that has been attributed to stronger immune suppression in the lung patients. EBV-SMT showed a higher incidence among kidney recipients than among lung recipients, suggesting that the degree of immunosuppression may be a less important factor in the development of EBV-SMT. EBV-SMT has most often been seen among lung transplant recipients with EBV mismatch., Conclusions: Because EBV-SMT is a rare tumor, its incidence, risk factors, and optimal management have not been well-defined and further study is needed., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Smooth muscle tumor of uncertain malignant potential (STUMP) is a rare diagnosis rendered when there is uncertainty concerning the biological potential of a smooth muscle tumor. The initial differential diagnosis is often broad, as tumors in this subgroup are morphologically heterogenous. Recent data suggest uterine inflammatory myofibroblastic tumors (IMTs) with anaplastic lymphoma kinase (ALK) rearrangement may be misclassified as STUMPs, but the extent to which this occurs has not been examined. We identified 60 female patients with tumors previously diagnosed as STUMP (48 cases) or prospectively considered for the diagnosis of STUMP (12 cases). Each case underwent histologic review, ALK immunohistochemistry (IHC) and confirmatory break-apart fluorescence in situ hybridization (FISH) for ALK if immunoreactive. Six of the 43 (14%) uterine and cervical tumors were ALK IHC positive, whereas tumors at all other sites were ALK IHC negative. Myxoid features, although limited in some cases, were present in all 6 ALK IHC positive tumors, representing 35% (6/17) of tumors displaying myxoid features at uterine and cervical sites. All ALK immunoreactive tumors were confirmed to have ALK rearrangements by FISH with 1 tumor showing numerous (3 to 8) 3' ALK signals, an unusual FISH pattern not previously described in uterine IMTs. Two patients developed recurrent disease and were treated with ALK-targeted therapy with initial response. Our data demonstrate that a significant proportion of uterine and cervical tumors considered to be STUMPs are ALK-positive by IHC and FISH. Future screening of all uterine and cervical mesenchymal tumors under consideration for the diagnosis of STUMP, particularly those with myxoid features, is recommended to identify ALK-rearranged IMTs that could potentially be treated with targeted therapy using tyrosine kinase inhibitors.

We examined the value of targeted molecular screening for the identification of uterine anaplastic lymphoma kinase (ALK)-rearranged mesenchymal tumors, including ALK immunohistochemistry followed by molecular genetic testing, in all uterine leiomyosarcomas and STUMPs (smooth muscle tumors of uncertain malignant potential). All leiomyosarcoma and STUMP cases diagnosed in a 10-year period (2006-2016) at Charles University Faculty of Medicine in Pilsen were retrieved and reviewed. Of 23 cases, one case (LMS [leiomyosarcoma]) was positive for ALK rearrangement, namely, PPP1CB-ALK fusion gene. No specific histologic features (i.e., lymphocytic infiltrate and stromal edema) were observed in this case. This suggests that inflammatory myofibroblastic tumor (IMT)-like histologic features may not be an initial reliable screening tool in identifying uterine IMT cases. Thus, we proposed a two-step IHC and molecular genetic testing (as a reflex test) for IMT in all uterine LMS and STUMP cases. This will enhance the proper detection of such tumors at the population level and ultimately offer patients available targeted therapies.