Stromal Nodules Research Articles

Frequency and Spectrum of Non-Malignant Lesions in Abdominal Hysterectomy Specimens

Objective: To determine the histological spectrum of non-malignant lesions in abdominal hysterectomy specimens from women of reproductive age group. Study Design and Setting: This was a descriptive cross-sectional study carried out at a private hospital in Karachi from December 2018 to December 2019. Methodology: The uterine specimens of patients (n=262) between the ages of 24 to 55 years were collected. Hysterectomies done due to any benign uterine disease were included in the study. Hysterectomies due to malignant causes were excluded. Pathological diagnosis was done on light microscopy using routine hematoxylin and eosin staining technique. Data collected during the study period included patient's age, clinical history/diagnosis and histological diagnosis. On receiving the hysterectomy specimens as per protocol, specimens were immediately put in 10% formalin, appropriately labeled for patient’s name, gender, age and procedure. In histopathology lab, grossing of the specimens was done using standard protocols. Frequency and variables were analyzed by using descriptive statistics of SPSS-version 22. Results: Total n=262 hysterectomies were received. Mean age of all the patients was 34.7 years ±7.8. Non-malignant uterine pathologies on histopathology included 124(47.7%) leiomyomas, 52(20%) adenomyosis, 32(12.3%) endometrial polyps, 16(6.2%) endometrial hyperplasia, 6(2.3%) endometritis, 3(1.2%) disordered proliferative endometrium and 1(0.4%) endometrial stromal nodule. Rest of the cases showed normal phases of endometrial cycle. Only two cases (0.76%) out of 262 received as clinically benign uterine disease, were diagnosed as malignant on histopathology. Conclusion: Leiomyoma is the most common uterine pathology diagnosed in clinical setting as well as encountered at histopathological examination followed by Adenomyosis and endometrial polyps in women of reproductive age group in Pakistan.

SATB2 Expression in Uterine Sarcoma: A Multicenter Retrospective Study.

Uterine sarcomas represent a clinical challenge because of their difficult diagnosis and the poor prognosis of certain subtypes. The aim of this study was to evaluate the expression of the special AT-rich sequence-binding protein 2 (SATB2) in endometrial stromal sarcoma (ESS) and other types of uterine sarcoma by immunohistochemistry. We studied the expression of SATB2 on 71 full tissue sections of endometrial stromal nodule, low-grade ESS, uterine leiomyomas and leiomyosarcoma, undifferentiated uterine sarcoma, adenosarcoma, and carcinosarcoma samples. Nuclear SATB2 expression was then evaluated in an extended sample set using a tissue microarray, including 78 additional uterine tumor samples. Overall, with a cut-off of ≥10% of tumor cell staining as positive, the nuclear SATB2 score was negative in all endometrial stromal nodule samples (n=10) and positive in 83% of low-grade ESS samples (n=29/35), 40% of undifferentiated uterine sarcoma (n=4/10), 13% of leiomyosarcoma (n=2/16), 14% of adenosarcoma (n=3/22), and 8% carcinosarcoma (n=2/25) samples. Furthermore, in ESS patients, direct comparison of nuclear SATB2 scores with clinicopathologic parameters and other reported biomarkers such as progesterone receptor and estrogen receptor showed that nuclear SATB2 was associated with PR expression and a decreased risk of disease-specific death (odds ratio=0.06, 95% confidence interval=0.04-0.81, P=0.04). Our data suggest that SATB2 could be a marker with relative sensitivity (83%) for distinguishing between endometrial stromal nodule and ESS with potential prognostic value.

Update on Endometrial Stromal Tumours of the Uterus.

Endometrial stromal tumours (ESTs) are rare, intriguing uterine mesenchymal neoplasms with variegated histopathological, immunohistochemical and molecular characteristics. Morphologically, ESTs resemble endometrial stromal cells in the proliferative phase of the menstrual cycle. In 1966 Norris and Taylor classified ESTs into benign and malignant categories according to the mitotic count. In the most recent classification by the WHO (2020), ESTs have been divided into four categories: Endometrial Stromal Nodules (ESNs), Low-Grade Endometrial Stromal Sarcomas (LG-ESSs), High-Grade Endometrial Stromal Sarcomas (HG-ESSs) and Undifferentiated Uterine Sarcomas (UUSs). ESNs are clinically benign. LG-ESSs are tumours of low malignant potential, often with indolent clinical behaviour, with some cases presented with a late recurrence after hysterectomy. HG-ESSs are tumours of high malignant potential with more aggressive clinical outcome. UUSs show high-grade morphological features with very aggressive clinical behavior. With the advent of molecular techniques, the morphological classification of ESTs can be integrated with molecular findings in enhanced classification of these tumours. In the future, the morphological and immunohistochemical features correlated with molecular categorisation of ESTs, will become a robust means to plan therapeutic decisions, especially in recurrences and metastatic disease. In this review, we summarise the morphological, immunohistochemical and molecular features of ESTs with particular reference to the most recent molecular findings.

Detection of MEAF6-PHF1 translocation in an endometrial stromal nodule.

Endometrial stromal nodule (ESN) and low-grade endometrial stromal sarcoma (LG-ESS) are rare uterine tumors known as endometrial stromal tumors (ESTs). In addition to their similarity in morphological features, recent studies have shown that these two tumors share common genetic alterations. In particular, JAZF1-SUZ12 fusion is found with high frequency in both ESN and LG-ESS. In LG-ESS, some minor fusions have also been described, which include rearrangements involving PHF1 and its partner genes, such as JAZF1, EPC1, MEAF6, BRD8, EPC2, and MBTD1. Because of the rarity of ESN, genetic alterations other than JAZF1 fusion have not been investigated in detail. In this study, we performed a next-generation sequencing-based analysis in a case of ESN with peripheral metaplastic bone formation and detected MEAF6-PHF1 fusion, which has been reported in a small subset of uterine LG-ESSs and soft tissue ossifying fibromyxoid tumors. The finding that MEAF6-PHF1 fusion is a background genetic abnormality detected both in ESN and LG-ESS, along with JAZF1-SUZ12, provides further support for the similarity and continuum between these two types of ESTs. Furthermore, the association between metaplastic bone formation and MEAF6-PHF1 fusion may not be limited to soft tissue tumors.

Uterine Endometrial Stromal Tumors With Limited Infiltration: First Report of a Case Series Indicating Potential for Malignant Behavior.

The distinction between a uterine endometrial stromal nodule (ESN) and low-grade endometrial stromal sarcoma (LGESS) is based on the nature of the interface between the lesion and the surrounding myometrium and the presence or absence of vascular invasion. Most LGESS exhibit widespread irregular myometrial invasion with or without vascular invasion, whereas ESNs are well-circumscribed without vascular invasion. Tavassoli and Norris proposed that minor marginal irregularity (up to 3 protrusions, each <3 mm beyond the main mass) is allowable in an ESN and these criteria have been incorporated into the World Health Organization Classification. There is a small group of neoplasms with marginal irregularity greater than that allowable in ESN but without the widespread myometrial infiltration typical of most LGESS. Such neoplasms have been categorized as endometrial stromal tumor with limited infiltration but there have been no studies which have provided follow-up in this group of neoplasms. We aimed to determine the clinical behavior of this uncommon group of neoplasms. From a series of 19 endometrial stromal tumors with limited infiltration, mainly from consultation practice, we obtained follow-up information in 16 cases by contacting referring pathologists and clinicians. The patient age ranged from 32 to 84 yr (median: 54 yr) and follow-up ranged from 16 to 187 mo (median: 52 mo). Two of 16 patients (12.5%) developed metastatic disease to the small intestine and peritoneum (1 case-metastasis at 23 mo) and bone and lung (1 case-humeral metastasis at 135 mo; lung and sacral metastases subsequently). No patient died from disease during the follow-up period. A small percentage of endometrial stromal tumors with limited infiltration exhibit malignant behavior with distant metastasis. Such neoplasms should be regarded as potentially malignant and the term LGESS with limited infiltration is an appropriate designation.

Endometrial stromal nodule: report of 8 cases and literature review

Endometrial stromal nodule: report of 8 cases and literature review

Pneumothorax presentation in endometrial sarcoma patients receiving chemotherapy: A case series

Endometrial stromal sarcomas (ESS) account for 10-15% of uterine malignancies and are classified into four categories: endometrial stromal nodule (ESN), low-grade endometrial stromal sarcoma (LG-ESS), high-grade endometrial stromal sarcoma (HG-ESS) and undifferentiated uterine sarcoma (USS). Depending on stage, ESS is treated with surgery, hormone therapy, chemotherapy or targeted therapy. A rare complication of ESS with metastatic pulmonary disease is recurrent, bilateral pneumothoraces. The current literature has reported on patients with ESS who either presented with pneumothoraces at their initial diagnosis, and thus were untreated, or after treatment with surgical resection and hormone therapy. There have been no case reports of patients with ESS who presented with pneumothoraces while receiving chemotherapy. Furthermore, there have been no reported cases of patients with HG-ESS presenting with this rare complication. We would like to expand the literature by reporting on two patients with HG-ESS who presented with pneumothoraces while concurrently receiving chemotherapy.

Clinicopathological Correlation of Uterine Corpus Tumors: A Study of 433 Cases

Uterine corpus tumors are one of the most common reasons for morbidity and mortality of women around the world, and histopathological diagnosis is the key for better management of the patients. To study the histopathology of uterine tumors, classify them as per WHO 2014 classification and correlate with clinical parameters. A five-year study was conducted on 433 histopathologically diagnosed cases of uterine corpus tumors. Benign tumors were the most common (95.6%) followed by malignant (3.9%) and borderline (0.5%). Leiomyoma was the most common benign tumor (91.2%). Majority of the cases were multiparous females (88.6%) in fourth and fifth decades of life (77%) and presenting with heavy menstrual bleeding (35.9%). The most location was intramural (68.9%). Cellular leiomyoma (1.8%) was the most common histologic variant; the secondary change was hyalinization (27.8%). Endometrial carcinoma was the most common malignant tumor (3%) followed by leiomyosarcoma (0.5%) and adenosarcoma (0.2%). Majority of the women with endometrial carcinoma were multiparous (76.9%) and belonging to the age-group of 50–59 years (38.4%). The most common symptom was postmenopausal bleeding (76.9%). Endometrioid carcinoma grade I (75%) was the most common type of endometrial carcinoma. Other lesions were adenomyoma (N = 17), STUMP (N = 2), and one case each of adenomatoid tumor, endometrial stromal nodule and secondary tumor. Benign tumors were more common than malignant tumors. Leiomyoma was the most common benign tumor, and endometrial carcinoma was the most common malignant tumor. Many uterine tumors present with similar clinical features. However, histopathology plays an important role in the accurate diagnosis of different types of tumors and thus helps in providing the patient with appropriate management.

Electrophysiological differences between typical and dense benign prostatic hyperplasia tissues retrieved after holmium laser enucleation of the prostate

Electrophysiological differences between typical and dense (beach ball) benign prostatic hyperplasia (BPH) tissues were investigated using a needle device with a micro-electrical impedance spectroscopy (µEIS) sensor. Ten pieces of typical BPH tissues and beach balls were collected from ten patients during the morcellation procedure of Holmium laser enucleation of the prostate. Their impedance was measured at a frequency range from 100 to 1 MHz using the µEIS-on-a-needle (µEoN). The impedance data (magnitude) were compared between the two tissue types and their correlation with the pathologic features was investigated. The mean magnitude of the beach balls tended to be larger than that of the typical BPH tissues at all investigated frequencies. Notably, significantly larger magnitudes were observed in the beach balls at the frequencies higher than 15.9 kHz (p ≤ 0.02). The variation of mean log-transformed magnitudes by frequency was significantly different between both tissue types (p < 0.001). The pathologic features of the beach balls presented pure stromal nodules of nodular hyperplasia, while the typical BPH tissues presented mixed epithelial-stromal nodules. The impedance difference between typical BPH tissues and beach balls is assumed to be attributed to the amount of their stromal content.

Mesenchymal and mixed uterine tumors : Current overview and practical aspects

Benign leiomyomas are the most frequent mesenchymal tumors of the uterus. In contrast, uterine sarcomas are very rare. Leiomyosarcomas are the most frequent sarcomas followed by endometrial stromal sarcomas (ESS). Leiomyosarcomas are characterized by marked nuclear atypia and high mitotic count and may also show tumor cell necrosis and myometrial and vascular invasion. For cases of diagnostic uncertainty, the category of smooth muscle tumor of uncertain malignant potential (STUMP) may be considered but should be rarely used. Besides low-grade ESS and stromal nodules, acategory of high-grade ESS was reconsidered by the WHO in 2014. High-grade ESS are characterized by fibromyxoid and round cell histology, myoinvasive growth, and immunoreactivity for cyclin D1 and BCOR and distinct gene fusions involving YWHAE and BCOR, respectively. The very rare undifferentiated uterine sarcomas need to be redefined due to overlap with high-grade ESS. Uterine tumors resembling ovarian sex cord tumors (UTROSCT) rarely behave malignant, but need to be distinguished from endometrial carcinomas. Mixed epithelial and mesenchymal tumors of the uterus are rare with carcinosarcomas occurring more frequently than adenosarcomas. For prognosis of adenosarcomas the recognition of sarcomatous overgrowth is crucial. Carcinosarcomas are histologically heterogeneous although genetically clonal; biologically they are considered as undifferentiated carcinomas. There will be an increasing importance of molecular pathology for the classification of rare and unusual mesenchymal uterine tumors.

Recent advances in the histological and molecular classification of endometrial stromal neoplasms.

This review addresses known features and recent developments in the histological, immunohistochemical, and molecular characterization of endometrial stromal neoplasms. We discuss the spectrum of these tumors, from the benign endometrial stromal nodule to low-grade endometrial stromal sarcoma to uterine undifferentiated sarcomas with a special emphasis on the expanding group of high-grade stromal sarcomas, recently added to the 2014 WHO classification, not only discussing the well-established YWHAE-FAM22 tumors but also two new groups, presenting with BCOR alterations including those with BCOR tandem internal duplications or NTRK fusions. It is likely that this high-grade category of endometrial stromal tumors will expand as increasing molecular data is available.

Proliferative Lesions of the Endometrium of 50 Four-Toed Hedgehogs ( Atelerix albiventris).

Uteri from 50 four-toed hedgehogs ( Atelerix albiventris) with clinical signs of uterine disease were histopathologically examined. Sixteen animals (32%) were diagnosed with endometrial hyperplasia, 7 animals (14%) were diagnosed with endometrial polyp, and 27 animals (54%) were diagnosed with endometrial neoplasia. The mean ages of the animals with endometrial hyperplasia, polyp, and neoplasia were 28.7 months, 29.4 months, and 25.2 months, respectively. The neoplasms were classified into 7 endometrial mixed tumors, 12 endometrial stromal nodules, and 8 endometrial stromal sarcomas. However, the endometrial stromal nodules and endometrial stromal sarcomas often developed within or were contiguous with an endometrial polyp or mixed tumor. Interestingly, the stromal tumors and the stromal components of the endometrial polyp and mixed tumor displayed extraendometrial differentiation (eg, into adipocytes, granular cells, smooth muscle cells, and osteoid tissue). The endometrial stromal sarcomas exhibited severe cellular atypia and invaded subendometrial tissue. Immunohistochemical examinations demonstrated that the stromal cells of the hyperplastic lesions as well as the neoplastic lesions were positive for CD10, the progesterone receptor, and Wilms tumor 1. The four-toed hedgehog develops unique uterine neoplasms that are mainly composed of endometrial stromal cells and probably arise from endometrial polyps and/or mixed tumors.

A retrospective study of disease incidence in African pygmy hedgehogs (&lt;i&gt;Atelerix albiventris&lt;/i&gt;)

The African pygmy hedgehog (Atelerix albiventris) is becoming a popular pet in Japan. The aim of this study was to determine the incidence of various diseases in African pygmy hedgehogs. We histologically investigated 105 samples from 100 privately-owned pet African pygmy hedgehogs that were submitted to two laboratories (North Lab and Patho Labo) between 2012 and 2017. Tissues submitted for this study were taken from female reproductive organs (33 cases; 31.43%), skin (20 cases; 19.05%), and the oral mucosa (19 cases; 18.1%). The most common histological diagnoses included endometrial stromal nodules identified as benign uterine neoplasia (14 cases; 13.33%); endometrial polyps identified as non-neoplastic polyps (7 cases; 6.67%), gingival hyperplasia and chronic suppurative inflammation in the oral mucosa (11 cases; 10.48%), fibrosarcomas in the skin (8 cases; 7.62%), and mammary tumors (8 cases; 7.62%). In this study, lymphoma and oral squamous cell carcinoma were less common than in the previous reports. The present study revealed the disease prevalence in captive African pygmy hedghogs that were histopathologically examined.

CyclinD1 Positive High-Grade Endometrial Stromal Sarcoma: a Fascinating Entity!

The 2014 WHO classifies endometrial stromal tumours into endometrial stromal nodule(ESN), low-grade endometrial stromal sarcoma (LGESS), high-grade endometrial stromalsarcoma (HGESS), and undifferentiated uterine sarcoma (UUS). LGESS and HGESS are histomorphologically, immunohistochemically and genetically distinct from each other.A 51-year-old postmenopausal lady presented to us with vaginal bleeding. Radiological findings revealed a well defined heterogeneous lesion involving the whole of uterus.Hysterectomy revealed a large polypoidal tumour, occupying the entire uterine cavity.Microscopically, the tumor was predominantly composed of epithelioid cells with very fewintervening spindle cell areas. Immunohistochemically, epithelioid cells were diffusely positive for cyclinD1, while were negative for CD10, ER, PR.Diagnosis of cyclinD1 positive HGESS was rendered. This case highlights the importance of performing cyclinD1 immunostaining in diagnosing HGESS. DOI:10.21276/APALM.1530

Magnetic resonance imaging features of endometrial stromal sarcoma: a case description.

Endometrial stromal sarcoma (ESS) originates from mesenchyma or naive mesenchyma, accounting for only 0.2% of all uterine malignancies and 10–15% of uterus sarcoma. The annual incidence rate is 1–2 per million and the average age is 40–45 years old (1,2). ESS has a more preferable prognosis when compared with the more common endometrial carcinomas of epithelial origin. In 2003, ESS was classified into endometrial stromal nodule, low-grade endometrial stromal sarcoma (LGESS), high-grade ESS, undifferentiation endometrial stromal sarcoma (UES) by WHO. Early detection is necessary so to increase survive rate. Generally on magnetic resonance imaging (MRI) ESS shows the uterine body is enlarged with a well-circumscribed mass of inhomogeneous signals. In some circumstance, ESS presents hyperintensity on T2-weighted images, and isointensity relative to the myometrium on T1-weighted images. Moreover, obvious hyperintensity was observed on diffusion weighted imaging (3-5). Interestingly, in some cases, ESS may have a characteristic low-intensity rim on T2-weighted images (6). We herein present a case of a LGESS.

Morcellating uterine mesenchymal tumors: The pathologist's view.

The study was conducted to delineate the histological problems in diagnosing uterine mesenchymal tumors in morcellated material. All cases of morcellated uteri performed between 2008 and 2014 were reviewed. The incidence of unexpected malignancy, defined as any neoplasm with a clear-cut diagnosis of leiomyosarcoma (LMS) or endometrial stromal sarcoma (ESS), was noted. Cases with absolute discrepancy between the diagnosis of the morcellated tumor and the subsequent diagnosis were also included in the study. Out of 631 cases, a final diagnosis of LMS or ESS was made regarding three and five tumors, respectively. Patient age ranged from 25 to 48 years. Two further cases initially diagnosed as ESS proved to be endometrial stromal nodules with smooth muscle differentiation. Two cases were diagnosed as smooth muscle tumors with uncertain malignant potential and the patients remain free of disease. One tumor was diagnosed as an endometrial stromal neoplasm and proved to be benign and finally a leiomyoma variant presented with presumed peritoneal disease. Both endometrial stromal and smooth muscle tumors with malignant behavior can be encountered at a young age. Because of the limitations in histological evaluation, morcellated tumors may be overdiagnosed or underdiagnosed by pathologists.

Endometrial stromal nodule in a woman with abnormal uterine bleeding and abdominal pain: a case report

Endometrial stromal nodule in a woman with abnormal uterine bleeding and abdominal pain: a case report

SF1 immunohistochemistry is useful in differentiating uterine tumours resembling sex cord-stromal tumours from potential histological mimics

The aim of this study was to perform an immunohistochemical comparison of uterine tumour resembling ovarian sex cord-stromal tumour (UTROSCT) and other uterine lesions with sex cord-like (SCL) differentiation. Six UTROSCTs and 10 potential histological mimics with focal SCL elements were examined, the latter comprising three endometrial stromal nodules, three low-grade endometrial stromal sarcomas, three Müllerian adenosarcomas, and one case of adenomyosis. All cases were stained immunohistochemically for SF1, FOXL2, calretinin and inhibin, and for the less specific markers smooth muscle actin, desmin, CD10, CD56, CD99, cytokeratin, oestrogen receptor and progesterone receptor. Three, four, six and three UTROSCT expressed SF1, FOXL2, calretinin and inhibin, respectively. However, calretinin staining was focal (≤50% cells positive) in five of the cases. Three potential histological mimics demonstrated calretinin, FOXL2 and/or inhibin staining but none was SF1 positive. Most cases in both groups expressed the less specific immunomarkers. SF1 and FOXL2 immunoreactivity in UTROSCT further supports the concept that these tumours demonstrate genuine sex cord-stromal differentiation. While calretinin was the most sensitive UTROSCT marker, staining was usually focal and expression was also seen in two of 10 potential histological mimics. SF1 staining was 100% specific for UTROSCT in this series but this finding should be confirmed in larger studies.

Mullerian Adenosarcoma Occurring in a Young Female and Originally Diagnosed as an Endometrial Stromal Nodule

Mullerian Adenosarcoma (MA) is most commonly encountered in postmenopausal females in the sixth decade of life. We present the case of a 21-year old female with a high BMI and a clinical presentation suggestive of polycystic ovarian disease; she presented with abnormal vaginal bleeding. A laparoscopy/hysteroscopy by her primary physician demonstrated an intracavitary and submucosal appearing mass which was clinically considered to be a polypoid submucosal leiomyoma. The patient underwent endometrial curettage. The specimen was comprised of multiple fragments of soft tan-red haemorrhagic tissues aggregating to 6.5 x 4.0 x 0.6 cm. An original diagnosis of endometrial stromal nodule was made on this material; however, on consultative review the diagnosis was changed to a mullerian adenosarcoma. No stromal overgrowth or heterologous differentiation was identified. Immunohistochemical studies demonstrated stromal cells were positive for oestrogen receptor (ER) and CD10. We emphasize the young age of this patient with a mullerian adenosarcoma as well as the pitfall of making a specific diagnosis of endometrial stromal neoplasms based on an endometrial curettage.

Molecular Cytogenetic Analysis of JAZF1, PHF1, and YWHAE in Endometrial Stromal Tumors: Discovery of Genetic Complexity by Fluorescence in Situ Hybridization

Diagnosis of endometrial stromal tumors (ESTs) can be challenging, particularly endometrial stromal sarcomas (ESSs) because of variable histologic appearance, long latency to recurrence, frequent metastases with unknown primary, and overlap with endometrial stromal nodules and undifferentiated uterine sarcomas. To enhance EST diagnosis, a break-apart strategy fluorescence in situ hybridization panel to detect JAZF1, PHF1, and YWHAE rearrangements was applied to a cohort of primary or metastatic endometrial stromal nodules, ESSs, or undifferentiated uterine sarcomas (36 cases for JAZF1, 24 of which were also assessed for PHF1 and YWHAE), 24 myometrium/endometrium controls, and 37 non-ESTs in the differential diagnosis. JAZF1 was the most frequently altered gene and occurred in all EST types, JAZF1 and/or PHF1 were mutually exclusive from YWHAE involvement, and uterine and extrauterine ESTs have a shared pathogenesis. We further defined frequency of these rearrangements and provided a resource demonstrating the signal complexity that can manifest when evaluating JAZF1. Rearrangement of JAZF1 occurred in 47% of ESTs, most (70%) of which had atypical patterns representing multiple structural alterations and/or more than one clone. YWHAE and PHF1 rearrangements each occurred in 8% of ESTs. An exceptional case was an ESS without JAZF1 or MEAF6 disruption that further disputes correlation of PHF1 involvement with the sex cord-like variant. These results expand our understanding of the genetic heterogeneity that defines ESTs.