OBJECTIVE: Histopathologic diagnosis of a subset of uterine smooth muscle tumors is challenging. We report a critical review regarding the clinicopathological point of view of 62 cases of subsequently recurred or metastasized leiomyoma.
METHODS: Medical records and glass slides of 62 cases of uterine smooth muscle tumor diagnosed as leiomyoma, which subsequently recurred or metastasized, were critically reviewed by pathologists specializing in gynecologic pathology and oncology.
RESULTS: In 47 (75.8%) of 62 cases, the diagnosis of leiomyoma was confirmed, including 11 intravascular leiomyomatosis (IVL) and benign metastasizing leiomyoma (BML). In 29 cases (46.8%) laparoscopic surgery was performed, of which morcellator without a bag was employed in 23 cases. Fifteen cases (24.2%) appeared to be underestimated and were re-classified as smooth muscle tumor of uncertain malignant potential (STUMP), leiomyosarcoma, or other malignant mesenchymal tumors. Recurrences in seven cases (11.3%) were interpreted to be a malignant transformation, and one STUMP recurred as STUMP.
CONCLUSIONS: The recurrence or metastasis in cases of \"leiomyoma\" is attributed to iatrogenic or under-evaluation of primary tumors, although a subset of cases is a rare example of biological progression.

Leiomyosarcoma (LMS) is the most common sarcoma in adults. Rarely, LMS dedifferentiates into an undifferentiated sarcoma. Very few cases of LMS with heterologous osteosarcomatous differentiation (OS) have been reported. The purpose of this study was to evaluate the clinicopathologic features of LMS with OS. Of 5570 LMS cases diagnosed from 2006 to 2022, 15 cases (0.2%) of LMS with OS were identified, affecting 13 females and 2 males; ages ranged from 32 to 66 years (median: 53 y). Ten tumors arose in the uterus, 2 in the retroperitoneum, and 1 each in the mesentery, mediastinum, and rectum. Primary tumors ranged from 7 to 20 cm (mean: 16 cm). The LMS components showed conventional spindle cell morphology in most cases; 3 cases showed marked pleomorphism; 3 cases contained an epithelioid component; and 1 case showed myxoid features. In 5 cases OS was identified in the primary tumor, whereas in 10 cases OS was first detected in metastases. One metastatic and 2 primary LMS showed both OS and chondrosarcomatous differentiation. Prominent osteoclastic giant cells were seen in the OS components in 11 cases. Mitotic activity ranged from 17 to 61/10 HPF with tumor necrosis in 10 cases. Twelve patients developed metastases; sites included lungs, diaphragm, kidney, adrenal glands, colon, small intestine, liver, bone, and pancreas. At last follow-up, 8 patients had died of disease, and 4 patients were alive with metastases. The interval between OS and death ranged from 3 weeks to 18 months (median: 6.5 mo). Development of OS in LMS is exceptionally rare. This form of heterologous differentiation may occur in both primary tumors and metastases. LMS with OS is highly aggressive with poor outcomes. Awareness of this phenomenon is important to avoid misdiagnosis as osteosarcoma.

OBJECTIVE: To evaluate the risk of encountering unexpected uterine smooth muscle tumors of uncertain malignant potential (STUMPs) or sarcomas during surgical treatment of mesenchymal tumors of the uterus using morcellation.
METHODS: Data were collected retrospectively from subjects who were pathologically diagnosed with uterine leiomyoma or its variants, STUMP or other premalignant mesenchymal tumors of uterus, or sarcoma during surgical treatment between July 2014 and June 2017.
RESULTS: A total of 3785 women were investigated; 2824 laparoscopic procedures (74.6%) were performed, and an electronic power morcellator was used in 1636 patients (43.2%). Sixteen women (0.42%) were diagnosed with STUMP and 14 (0.37%) were diagnosed with uterine sarcoma. The incidence rate of unexpected STUMP or uterine sarcoma was 0.61% (23 of 3785 women); unexpected STUMP in 13 (0.34%), and unexpected sarcoma was in 10 (0.26%). Moreover, the unexpected leiomyosarcoma rate was 0.08% (3 in 3785). The rate of unintended morcellation of STUMPs was relatively high at 0.26% (10 in 3785), however, that for uterine sarcomas was 0.05% (2 in 3785).
CONCLUSIONS: The risks of unintended morcellation were very low for sarcomas and STUMPs, although the risk of the latter was approximately 5-fold that of the former. To reduce the unintended dissemination of tumors, patients suspected of having malignancies should be provided adequate information regarding their treatment options as well as their associated risks. Meanwhile, improved preoperative screening methods for STUMP and sarcoma should be established.

Objective: To study the clinicopathological characteristics and immunohistochemical phenotype of phosphaturic mesenchymal tumor (PMT) . Methods: The clinicopathological data and immunohistochemical profiles were obtained retrospectively from 206 patients diagnosed with PMT at Peking Union Medical College Hospital (PUMCH) during July 2008 to September 2017, with a review of literature. Results: The mean age of PMT patients was 42 years (range 13 to 70 years), with a male to female ratio of 1.1∶1.0. All patients presented with different degree of bone pain, muscle weakness, shorten of stature, thoracic deformity and pathological fractures, with hypophosphatemia and high serum ALP. Phosphatemia returned to normal within 1 week after operation in all cases underwent complete tumor resection. The duration of osteomalacia before resection (documented in 197 cases) ranged from 20 days to 40 years (average 5.7 years). The average blood phosphorus concentration raised from 0.49 mmol/L to 0.92 mmol/L before and after tumor resection (P<0.01), with 147 cases (84.0%, 147/175) returned to normal range within 2 weeks. The rate or blood phosphorus concentration recovery in 15 days after operation was 79.6% in average, displayed significant differences between patients with complete resection and those with partial resection (85.4% vs. 21.1%, P<0.01). PMT lesions mainly involved lower extremities (55.8%), followed by head and neck (29.1%). In immunohistochemical study, all cases were positive for vimentin (100.0%), while most cases were positive for NSE (96.3%), CD56 (94.2%), FGF23(88.4%), CD68 (88.3%), D2-40 (70.9%), CD34 (23.1%), SMA (55.5%), bcl-2 (59.8%) and CD99 (47.1%). The Ki-67 positive index of tumor varied from less than 2% (51.4%), 3% to 10% (41.3%) to >10% (7.2%). Conclusions: PMT mainly occurs in lower limbs or head and neck, with unique clinical characteristics and blood biochemical indexes. The tumor expresses a variety of immunohistochemical markers, indicating the potential of multi-directional differentiation. Clinical profile, blood biochemistry testing and immunohistochemical phenotype is helpful for diagnosis of PMT.
目的： 探讨磷酸盐尿性间叶肿瘤(phosphaturic mesenchymal tumor, PMT)的临床特征及免疫组织化学表型。 方法： 回顾性分析2008年7月至2017年9月北京协和医院206例PMT的临床病理资料及免疫组织化学表型，并复习相关文献。 结果： 206例PMT患者男女比例1.1∶1.0，平均年龄42岁(范围13～70岁)。临床表现为不同程度的骨痛、乏力、活动受限，部分有身高变矮、胸廓变形、病理性骨折等。206例患者中，197例记录了术前骨软化症状持续时间(20 d至40年)，症状平均持续时间5.7年。血生化检测显示低血磷，高尿磷，高碱性磷酸酶(ALP)，而1，25(OH)(2)D(3)水平偏低。206例患者中190例有术前血磷结果，176例有术后血磷结果，175例有对应的手术前后血磷结果。手术前平均血磷浓度0.49 mmol/L，手术后平均血磷浓度0.92 mmol/L(P<0.01)；术后2周内血磷恢复至正常值的有147例(84.0%，147/175)，术后15 d血磷累积恢复率为79.6%；手术完全的PMT患者术后2周血磷累积恢复率为85.4%，手术不完全(肿瘤有残留)的PMT患者血磷累积恢复率约为21.1%(P<0.01)。PMT发病部位最常见于下肢(55.8%，115/206)，其次是头颈部(29.1%，60/206)。免疫组织化学染色结果显示，波形蛋白阳性率100.0%(166/166)，神经元特异性烯醇化酶阳性率96.3%(133/138)，CD56阳性率94.2%(162/172)，成纤维细胞生长因子-23阳性率88.4%(114/129)，CD68阳性率88.3%(91/103)，D2-40阳性率70.9%(78/110)，CD34阳性率23.1%(40/173)，平滑肌肌动蛋白阳性率55.5%(81/146)，bcl-2阳性率59.8%(101/169)，CD99阳性率47.1%(75/159)。Ki-67阳性指数≤2%者占51.4%(92/179)，3%～10%者占41.3%(74/179)，>10%者占7.2%(13/179)。 结论： PMT具有独特的临床及血生化特征，最常发生于下肢和头颈部；肿瘤细胞表达多种免疫组织化学标志物，提示具有多向分化潜能；临床与血生化表现以及免疫组织化学表型有助于PMT的正确诊断。.

Ectomesenchymal chondromyxoid tumor (ECT) is a rare benign neoplasm, often affecting the anterior dorsum of the tongue. To date, approximately 74 cases of lingual ECT have been published. This report describes, for the first time, the morphological and immunohistochemical features of a unique ECT case, which revealed diffuse infiltration by immune cells with a dendritic-like appearance inside the tumor proliferation. The significance of these findings and discussion about the tumor cell-immune cell interactions are presented.

Endometrial cancer is the most prevalent genital tract cancer in occident and the third most common cancer among women in Tunisia. It is dominated by carcinoma. The identification of prognostic factors allows a better understanding of its outcome and guides its therapeutic approach. We propose to describe the clinicopathological features and identify the histoprognostic factors of this cancer. It is a retrospective analysis of a series of 62 total hysterectomy specimens with bilateral salpingo-oophorectomy from women with primary carcinoma of the endometrium, colligated in Anatomy Laboratory and Pathology Salah Azaiz Institute of Tunis over a period of 5 years, from January 2003 to December 2007. The median age was 60 years. At the time of diagnosis, 25% of patients were nulliparous and 86% were menopaused. The endometrioid adenocarcinoma was the most common, accounting for 84% of cases (5% of them were grade 3). A myometrial invasion superior or equal to 50% was observed in 40% of cases. 42% of cases were classified as stage IA, 14% in stage IB, 16% in stage II, 18% stage III and 10% in stage IV. 22% of patients had nodal involvement. Overall survival at 5 years was 81%. In multivariate analysis, stage IV, nodal involvement and brachytherapy have influenced this rate. Event-free survival at 5 years was 71%. It was directly related to stage and nodal involvement. Stage, histological type, tumor grade, invasion of more than half of the myometrium and lymph node involvement were the most important adverse prognostic factors, dictating an appropriate management of these tumors.

Early response to induction chemotherapy is used in current European guidelines to evaluate the efficacy of chemotherapy and subsequently to adapt treatment in pediatric patients with rhabdomyosarcoma (RMS). However, existing literature on the prognostic value of early radiologic response on survival is contradictory; here the prognostic value is analyzed with data from the International Society of Pediatric Oncology (SIOP) Malignant Mesenchymal Tumor 95 (MMT-95) study.
This study examined 432 Intergroup Rhabdomyosarcoma Study Grouping III (macroscopic residue) patients enrolled in the SIOP MMT-95 study with a response assessment after 3 courses of chemotherapy (a 2-dimensional assessment). Patients with progressive disease (PD) after 3 courses of chemotherapy were excluded (n = 7). Failure-free survival (FFS) and overall survival (OS), calculated with the Kaplan-Meier method, were compared for 3 groups (complete response [CR]/partial response [PR], objective response [OR], and no response [NR]). The prognostic impact of early response was assessed through the calculation of Cox proportional hazards.
After 3 courses of chemotherapy, 85.2% of the patients had CR/PR, 8.6% had OR, and 6.3% had NR. For all patients, the 5-year FFS and OS rates were 60% (95% confidence interval [CI], 56%-65%) and 74% (95% CI, 70%-78%), respectively. However, a Cox proportional hazards regression analysis revealed no significant difference in FFS or OS between the response groups. The adjusted hazard ratios for an OR and NR were 1.09 (95% CI, 0.63-1.88) and 0.81 (95% CI, 0.39-1.67), respectively, for FFS and 0.91 (95% CI, 0.47-1.76) and 1.27 (95% CI, 0.61-2.64), respectively, for OS.
No evidence was found for the idea that early radiologic response to chemotherapy is prognostic for survival for patients with RMS. Treatment adaptation based on early response (except for patients with PD) should, therefore, no longer be incorporated into future studies. Cancer 2018;124:1016-24. © 2017 American Cancer Society.

Ectomesenchymal chondromyxoid tumor (ECT) is a rare benign neoplasm usually affecting the anterior dorsum of the tongue. Histopathologically, it is formed by spindle, round and/or polygonal cells embedded in a chondromyxoid matrix. Immunohistochemical positivity for vimentin, S-100 protein, glial fibrillary acid protein and neuron-specific enolase are helpful to confirm the diagnosis. There are 42 cases of ECT of the tongue reported in the English language literature, three of them showing no chondroid matrix. We describe two additional cases of ECT lacking the chondroid component, exhibiting areas of reticulated myxoid and cellular pattern. Considering the microscopical features, ECT can be classified in classic and \'chondroid-free\' variants, the latter including the reticulated myxoid and cellular patterns. It is important to consider that the cellular ECT usually exhibits predominance of an infiltrative atypical cellular component that may mimic a malignant tumor.

OBJECTIVE: To study the pathological and immunohistochemical features of upper gastrointestinal mesenchymal tumors (GIMTs) and compare them with endoscopic ultrasonographic (EUS) characteristics so as to evaluate the diagnostic value of EUS in upper digestive tract GIMTs.
METHODS: Seventy-two pathological specimens of upper digestive tract GIMTs (34 surgical specimens and 38 endoscopic mucosal resection (EMR) specimens) were collected. The pathological features and the expression of CD(117), CD(34), SMA and S-100 were observed by immunohistochemical method with light microscope. The pathological types and characteristics were determined by pathologists and compared with the layer of origin and sonographic characteristics determined with preoperative EUS.
RESULTS: In the 72 cases of upper digestive tract GIMTs, 37 cases were diagnosed as stromal tumor with pathological and immunohistochemical methods (51.4%); 21 of them were malignant, accounting for 56.7% of the stromal tumors. Thirty-four cases were diagnosed as leiomyoma (47.2%) and 1 case as schwannoma (1.4%). In the 72 GIMTs cases, 40 were esophageal GIMTs. EUS showed that 38 cases were originated from the muscularis mucosae layer; 33 of them were leiomyoma and 5 stromal tumor. The 2 cases originating from the muscularis propria layer which were both stromal tumors. Thirty-two cases were gastric GIMTs, EUS showed that 2 cases originating from the muscularis mucosae layer were gastric stromal tumor. Of the 30 cases originating from the muscularis propria layer, 28 cases were stromal tumor, 1 case was leiomyoma and 1 case was schwannoma. The sensitivity and the specificity of EUS in distinguishing benign and malignant stromal tumors according to sonographic characteristics were 81.0% and 93.8% respectively.
CONCLUSIONS: Stromal tumor is more common in stomach mesenchymal neoplasms and is more often originated from the muscularis propria layer in EUS; leiomyoma is more common in esophagus and is more often originated from the muscularis mucosae layer. The diagnostic sensitivity and specificity of EUS are high in distinguishing benign and malignant character of upper digestive tract GIMTs. EUS plays an important role in guiding the clinical management of upper digestive tract GIMTs.

Gastrointestinal stromal tumors (GISTs), KIT or platelet derived growth factor receptor alpha (PDGFRA) signaling driven mesenchymal tumors of the gastrointestinal (GI)-tract and abdomen, require a precise diagnosis so that the patients may benefit from the newly introduced tyrosine kinase inhibitor drugs. The limitations of the current main tools, KIT immunohistochemistry and KIT/PDGFRA mutation analysis, include lack of KIT expression and mutations in some GISTs. In this study we examined 1168 GISTs of different sites and histologic subtypes, and 672 other tumors and normal tissues for discovered on GIST-1 (DOG1) clone K9, a newly introduced immunohistochemical marker, a chloride channel protein. All GISTs and selected non-GISTs were independently evaluated for KIT. In the GI tract, Cajal cells and gastric surface epithelia were DOG1-positive. The overall sensitivity of DOG1 and KIT in GISTs was nearly identical: 94.4% and 94.7%, and results in GISTs were generally concordant. Gastric spindle cell GISTs was nearly uniformly positive for both markers, whereas DOG1 performed slightly better in gastric epithelioid GISTs that included PDGFRA mutant GISTs. In the intestinal GISTs, KIT was slightly more sensitive than DOG1. Negativity for both DOG1 and KIT was observed in 2.6% of GISTs of GI tract. KIT or PDGFRA mutations were detected in 11/24 DOG1-negative GISTs supporting the diagnosis of GIST. DOG1 expression was also generally present in extragastrointestinal and metastatic GISTs. DOG1 was highly specific for GIST, but exceptional DOG1-positive other mesenchymal tumors included uterine type retroperitoneal leiomyomas, peritoneal leiomyomatosis, and synovial sarcomas (positive in 5/42, 4/17, and 6/37 cases). Leiomyomas colonized by DOG1-positive Cajal cells should not be confused with GISTs. DOG1 positivity was relatively common in esophageal squamous cell and gastric carcinomas, whereas it was rare in colorectal carcinomas. DOG1 should be added into the diagnostic panel evaluating GI and other abdominal tumors, but limitations in its sensitivity and specificity should be recognized.