Prognostic relevance of early radiologic response to induction chemotherapy in pediatric rhabdomyosarcoma: A report from the International Society of Pediatric Oncology Malignant Mesenchymal Tumor 95 study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Endoscopic Ultrasonography in the Diagnosis and Treatment Strategy Choice of Esophageal Leiomyoma.

OBJECTIVES:: Esophageal leiomyoma is the most common benign tumor of the esophagus, and it originates from mesenchymal tissue. This study analyzed the clinicopathological characteristics of esophageal leiomyoma and aimed to evaluate the role of endoscopic ultrasonography in the diagnosis and treatment selection for these lesions. METHODS:: Two hundred and twenty-five patients who had suspected esophageal leiomyomas in endoscopic ultrasonography were enrolled at the Endoscopy Center of The First Affiliated Hospital, Zhejiang University from January 1st, 2009 to May 31th, 2015. The main outcomes included the demographic and morphological characteristics, symptoms, comparisons of diagnosis and treatment methods, adverse events, and prognosis. RESULTS:: One hundred and sixty-seven patients were diagnosed as having an esophageal leiomyoma by pathological examination. The mean patient age was 50.57±9.983 years. In total, 62.9% of the lesions originated from the muscularis mucosa, and the others originated from the muscularis propria. The median distance to the incisors was 30±12 cm. The median diameter was 0.72±0.99 cm. As determined by endoscopic ultrasonography, most existing leiomyomas were homogeneous, endophytic, and spherical. The leiomyomas from the muscularis mucosa were smaller than those from the muscularis propria and much closer to the incisors (p<0.05). SMA (smooth muscle antibody) (97.2%) and desmin (94.5%) were positive in the majority of patients. In terms of treatments, patients preferred endoscopic therapies, which led to less adverse events (e.g., intraoperative bleeding, local infection, pleural effusion) than surgical operations (p<0.05). The superficial leiomyomas presented less adverse events and better recovery (p<0.05) than deep leiomyomas. CONCLUSION:: Endoscopic ultrasonography has demonstrated high accuracy in the diagnosis of esophageal leiomyomas and provides great support in selecting treatments; however, EUS cannot completely avoid misdiagnosis, so combining it with other examinations may be a good strategy to solve this problem.

Endoscopic Ultrasonography in the Diagnosis and Treatment Strategy Choice of Esophageal Leiomyoma

OBJECTIVES: Esophageal leiomyoma is the most common benign tumor of the esophagus, and it originates from mesenchymal tissue. This study analyzed the clinicopathological characteristics of esophageal leiomyoma and aimed to evaluate the role of endoscopic ultrasonography in the diagnosis and treatment selection for these lesions. METHODS: Two hundred and twenty-five patients who had suspected esophageal leiomyomas in endoscopic ultrasonography were enrolled at the Endoscopy Center of The First Affiliated Hospital, Zhejiang University from January 1st, 2009 to May 31th, 2015. The main outcomes included the demographic and morphological characteristics, symptoms, comparisons of diagnosis and treatment methods, adverse events, and prognosis. RESULTS: One hundred and sixty-seven patients were diagnosed as having an esophageal leiomyoma by pathological examination. The mean patient age was 50.57±9.983 years. In total, 62.9% of the lesions originated from the muscularis mucosa, and the others originated from the muscularis propria. The median distance to the incisors was 30±12 cm. The median diameter was 0.72±0.99 cm. As determined by endoscopic ultrasonography, most existing leiomyomas were homogeneous, endophytic, and spherical. The leiomyomas from the muscularis mucosa were smaller than those from the muscularis propria and much closer to the incisors (p<0.05). SMA (smooth muscle antibody) (97.2%) and desmin (94.5%) were positive in the majority of patients. In terms of treatments, patients preferred endoscopic therapies, which led to less adverse events (e.g., intraoperative bleeding, local infection, pleural effusion) than surgical operations (p<0.05). The superficial leiomyomas presented less adverse events and better recovery (p<0.05) than deep leiomyomas. CONCLUSION: Endoscopic ultrasonography has demonstrated high accuracy in the diagnosis of esophageal leiomyomas and provides great support in selecting treatments; however, EUS cannot completely avoid misdiagnosis, so combining it with other examinations may be a good strategy to solve this problem.

Nonparameningeal head and neck rhabdomyosarcoma in children and adolescents: Lessons from the consecutive International Society of Pediatric Oncology Malignant Mesenchymal Tumor studies.

BACKGROUND: This article reports risk factors and long-term outcome in localized nonparameningeal head and neck rhabdomyosarcomas in children and adolescents from a combined dataset from 3 consecutive international trials. METHODS: Data from 140 children (9.3% of total) prospectively enrolled in the International Society of Pediatric Oncology Malignant Mesenchymal Tumor (SIOP-MMT)-84/89/95 studies were analyzed. RESULTS: Primary site was: superficial face in 46%; oral cavity (21%); neck (19%); and salivary glands (14%). Local control was achieved in 96%, but 49% relapsed (locoregionally 91%). At median follow-up of 10 years, 5-year overall survival (OS) was 74.7% (67.4% to 81.9%) and event-free survival 48.9% (40.6% to 57.2%), although this improved with successive studies. Radiotherapy (RT) as first-line treatment was independently prognostic for event-free survival (relative risk [RR] = 0.4 [range, 0.2-0.7]; p < .01) even if it did not impact OS (RR = 1 [range, 0.5-2]). CONCLUSION: High rates of locoregional relapse were seen in head and neck rhabdomyosarcoma that should be prevented by more frequent use of RT in this primary. © 2016 Wiley Periodicals, Inc. Head Neck 39: 24-31, 2017.

Critical reappraisal of primary osseous composite sarcoma (malignant mesenchymoma) - analysis of four cases and literature review.

In accordance with recent terminology, it is proposed that malignant mesenchymoma should be renamed 'composite sarcoma' and defined as 'a sarcoma composed of two or more cellular types each of which is sufficiently differentiated to permit clear recognition of its histogenetic type microscopically, immunohistochemically or ultrastructurally; excluding fibrosarcomatous and high-grade pleomorphic undifferentiated sarcomatous component, dedifferentiated sarcoma and the combination of osteosarcoma and chondrosarcoma which is regarded as a single histogenetic type'. Four cases of primary osseous composite sarcoma (POCS) were identified among 928 primary bone sarcomas. Their age ranged from 10 to 87 years, peak incidence in the second decade with equal sex distribution. Most presented with pain, commonest in the knee, affecting the metaphysis, appearing radiologically as expansile infiltrative osteolytic lesions with cortical erosion, periosteal reaction, variable extent of osteoblastic areas and soft tissue extension. All contained variable amounts of conventional high-grade osteosarcoma with or without chondrosarcoma component; the other constituents were liposarcoma, rhabdomyosarcoma and leiomyosarcoma. In all cases, Ki67 proliferative index was over 35%, there was no CDK4 and MDM2 amplification. The absence of low-grade component supported the de novo origin of POCS rather than derivation from divergent dedifferentiation. The two older patients with hitherto undescribed osteoleiomyosarcoma died 2 and 10 months after operation, whereas the two younger with osteorhabdomyosarcoma and osteoliposarcoma enjoyed disease-free survival at 16 and 6 years after chemotherapy despite the latter showing lung metastasis at presentation. Identification of the different lines of differentiation together with their approximate amounts and histological grades is therefore mandatory for POCS as multi-agent chemotherapy catered for each sarcoma component might offer hope for long-term disease-free survival.

[Diagnosis and treatment of prostatic malignant mesenchymal tumors: Analysis of 20 cases].

OBJECTIVE: To explore the diagnosis, treatment, and prognosis of prostatic malignant mesenchymal tumors (PMMT). METHODS: We retrospectively analyzed the clinical and follow-up data about 20 cases of PMMT and reviewed the literature relevant to the diagnosis, treatment, and prognosis of the disease. RESULTS: Based on the results of pathology and immunohistochemistry, the 20 PMMT cases included leiomyosarcoma (n = 7), rhabdomyosarcoma (n = 5), prostatic stromal sarcoma (n = 3), chondrosarcoma (n = 1), and undifferentiated PMMT (n = 4). Twelve of the patients were treated by radical prostatectomy (3 concurrently by sigmoid colostomy and 1 by cystostomy), 2 by pelvic tumor resection following arterial embolization, 1 by total pelvic exenteration, 1 by colostomy with pelvic lymph node biopsy, and 4 by conservative therapy because of metastasis to the lung, pelvis and bone. Of the 20 patients, 9 died of systemic metastasis within 3 months after treatment, 3 died at 6, 7, and 14 months, respectively, 3 survived with tumor for 5, 11, and 12 months, respectively, 2 survived without tumor for 12 and 24 months so far, all subjected to periodic chemotherapy postoperatively, and 3 lost to follow-up. CONCLUSION: PMMT is a tumor of high malignancy and rapid progression, for which transrectal ultrasound-guided biopsy remains the main diagnostic method. The clinical stage of the tumor is an important factor influencing its prognosis and the survival rate of the patients can be improved by early diagnosis and combined therapy dominated by radical prostatectomy.

Tumor-Induced Osteomalacia: an Up-to-Date Review.

Tumor-induced osteomalacia (TIO) is a paraneoplastic syndrome resulting in renal phosphate wasting and decreased bone mineralization. TIO is usually induced by small, slowly growing tumors of mesenchymal origin (phosphaturic mesenchymal tumor mixed connective tissue variant [PMTMCT]). Nonspecific symptoms including fatigue, bone pain, and musculoskeletal weakness make the diagnosis elusive and often lead to a delay in treatment. The prognosis of TIO is excellent following complete resection of the neoplasm, which leads to the rapid and complete reversal of all symptoms. If the tumor cannot be detected, treatment relies on supplementation with phosphate and active vitamin D compounds. Subsequent radiotherapy in case of incompletely resected tumors or definitive radiotherapy in unresectable tumors is an important treatment option to avoid recurrence or metastasis even though this occurs rarely. Due to the risk of recurrence or late metastases, long-term monitoring is required even in TIO patients diagnosed with a benign tumor.

Conservative approach in localised rhabdomyosarcoma of the bladder and prostate: results from International Society of Paediatric Oncology (SIOP) studies: malignant mesenchymal tumour (MMT) 84, 89 and 95.

BACKGROUND: The three sequential SIOP MMT studies provide the largest dataset available to date, to define the patient and tumour characteristics, treatment modalities and event-free and overall survival for children with non metastatic rhabdomyosarcoma (RMS) of the bladder and/or prostate (BP). PROCEDURE: The combined dataset of 172 patients with BP RMS treated on the SIOP MMT 84, 89 and 95 studies was reviewed to determine tumour characteristics, details of treatment and outcome. RESULTS: Median age at diagnosis was 2.5 years (range 2 months-17.8 years) and 138 (79%) were males. Median follow-up was 11.4 years (range 3 months-22 years). The 5-year overall survival of the combined cohort was 77% (CI 70-83%). The 5-year event-free survival was 63% and included 7 patients (4%) who did not achieve complete remission (CR), and 57 (33%) who relapsed. Age ≥ 10 years (RR 3.7) and alveolar pathology (RR 3.3) were identified as independent prognostic factors on multivariate analysis. Fifty-nine (50%) of the 119 survivors were cured without significant local therapy, improving from 31% in MMT84 study to 61% in MMT95 study. CONCLUSION: The clinical strategy of the MMT studies aims to minimise the burden of therapy whilst maintaining survival rates. Overall survival is comparable to that of other international groups, despite the lower use of radiotherapy and or radical surgery, although number of events experienced is higher. Further assessment of the late effects of therapy is required to confirm whether this approach results in lower morbidity in the long-term.

Complex analysis of a recurrent pleomorphic hyalinizing angiectatic tumor of soft parts.

Pleomorphic hyalinizing angiectatic tumor of soft parts is a recently recognized, low-grade mesenchymal neoplasm of uncertain lineage. It is characterized by clusters of ectatic, fibrin-lined, thin-walled vessels surrounded by pleomorphic but mitotically inert spindled cells with frequent intranuclear inclusions and a variable inflammatory component. Here, we report a case of recurrent pleomorphic hyalinizing angiectatic tumor in a 37-year-old white woman. Touch imprint cytologic analysis revealed oval and spindled cells with fine chromatin, occasional prominent intranuclear inclusions, and intracytoplasmic pigment. The histologic features of the cells constituting the bulk of tumor were those characteristic of a putative precursor lesion ("early pleomorphic hyalinizing angiectatic tumor") as well as another recently described entity known as hemosiderotic fibrohistiocytic lipomatous lesion. Cytogenetic analysis revealed 2 unbalanced translocations involving chromosomes 1 and 3 and chromosomes 1 and 10, with a karyotype of 45,XX,der(1)t(1;3)(p31;q12),-3,der(10)t(1;10)(p31;q25)[11]/46,XX[4], thus suggesting that this disease is neoplastic. The controversies in classification of these lesions are also discussed.

A rare case of malignant pediatric ectomesenchymoma arising from the falx cerebri.

Malignant ectomesenchymoma is a rare tumor arising from mature ganglion cells with immature myogenous elements, with only 4 pediatric intracranial cases having been previously reported. The authors report a rare case of intracranial malignant ectomesenchymoma originating from the falx cerebri in a 10-year-old boy. The patient presented with a 2-week history of headache, nausea, and blurry vision, with mild lateral gaze diplopia. A CT scan revealed a solitary 7.2 × 3.8-cm dural-based mass that extended along the falx. No metastatic disease was identified, and the lesion was grossly resected without complication. Pathological investigation identified single and small groups of cells in a myxoid background, with polygonal or spindle-shaped cells containing eccentric nuclei and prominent nucleoli. Immunohistochemical staining of some cells was positive for smooth-muscle actin, CD99, and vimentin, whereas other cells (often process forming) were positive for S100 protein, synaptophysin, and neurofilament protein. Staining was negative for CD138, CD45, α-fetoprotein, CK AE1/3, glial fibrillary acidic protein, CK7, CK20, CD31, CD34, myoD, and desmin. Normal immunopositivity was seen for INI-1. The Ki 67 immunostaining had < 25% reactivity. The patient was treated with a sarcoma-based chemotherapy regimen and radiation to the craniospinal axis, and was found to be without recurrence or metastatic disease at 20 months.

Primitive myxoid mesenchymal tumor of infancy: a report of a further case with locally aggressive behavior.

We report a case of an 8-month-old child with a primitive myxoid mesenchymal tumor of infancy arising in the thenar eminence. The lesion recurred after conservative excision and was ultimately nonresponsive to chemotherapy, necessitating partial amputation. The patient remains free of disease 5 years after this radical surgery. This is the 1st report of such a tumor since it was initially described by Alaggio and colleagues in 2006. The pathologic differential diagnosis is discussed.

Desmoid tumor: from surgical extirpation to molecular dissection.

PURPOSE OF REVIEW: Desmoid tumors are associated with a variable and unpredictable clinical course. Surgery is the therapeutic mainstay, but there has been much discussion of late regarding its proper application. Little is known regarding the molecular determinates of desmoid tumor behavior. Some recent work has focused on the role of beta-catenin in desmoid tumor biology. RECENT FINDINGS: Given the variable clinical course of desmoid tumors, the interpretation of factors classically associated with recurrence such as microscopic status of margins appears more nuanced that previously thought. The application of multidisciplinary assessment with multimodality treatment, including surgery, radiation and systemic therapies may underlie these changes and now form the basis of care for this tumor. The precise CTNNB1 mutation present appears to be strongly predictive of recurrence after initial resection in one large, retrospective, multivariate analysis. SUMMARY: Establishing the population benefiting most from various treatment modalities and combinations is critical for progress in this disease. Assessment and treatment of individual patients in a multidisciplinary setting is critical to achieve the most favorable outcome. Additional study of the molecular determinates of desmoid behavior is needed to guide therapeutic selection.

The ectomesenchymal chondromyxoid tumor: a review.

The ectomesenchymal chondromyxoid tumor is a relatively recently described neoplasm that appears to involve uniquely the oral cavity, particularly the tongue. Thirty well-accepted cases have been reported since the initial description of this lesion in 1995. While a wide age range (9-78 years) has been documented, most of these tumors are diagnosed from the third to sixth decades of life. No sex predilection is seen. The size of the neoplasm is typically <2 cm, and most affect the anterior dorsal tongue. The duration of the lesion was difficult to gauge, probably due to the asymptomatic nature of the process. Some tumors, however, were well documented to have been present for as long as 10-20 years. Histopathologically, the ectomesenchymal chondromyxoid tumor is characterized by a well circumscribed, but unencapsulated, lobular growth pattern. Varying degrees of cellularity are noted, with the lesional cells often set in a myxoid, chondroid or hyalinized background. Immunohistochemical studies reveal positivity of the lesional cells for antibodies directed against glial fibrillary acidic protein, cytokeratins, S-100 protein and CD-57 in the majority of tumors. Treatment consists of conservative surgical excision, and while recurrence is possible, it has been noted in <10% of reported cases.

Syndromic presentation of a pleuropulmonary blastoma associated with congenital cystic adenomatoid malformation. A case report.

Pleuropulmonary blastoma (PPB) is a rare malignant mesenchymal pediatric tumor with a well-recognized association with congenital cystic adenomatoid malformation (CCAM). Recently, it has been described in a patient with CCAM, multiple jejunal polyps, and cystic nephroma. We describe a similar case of a unique presentation of PPB, arising in association with CCAM and with a history of intussception caused by multiple small bowel polyps.

[Recurrent pericarditis revealing a malignant mediastinal mesenchymoma]. / Péricardite récidivante révélatrice d'un mésenchymome malin du médiastin.

INTRODUCTION: The malignant mesenchymoma is a malignant tumour composed of two or more types of non-differentiated tissue, associated with fibrosarcomatous elements. Its mediastinal localisation is exceptional. OBSERVATION: In a 65 year-old woman, recurrent pericardial effusion revealed a malignant mesenchymoma measuring 11 x 9 x 4 cm, located in the mediastinum and extending towards the pericardium. The histological examination of the surgical piece showed the predominance of an osteo-sarcomatous component. Complete resection was performed with partial pericardectomy, followed by adjuvant radiotherapy. CONCLUSION: Malignant mediastinal mesenchymoma is an exceptional tumour. Its diagnosis is based on anatomopathological study of a mass of anarchic composition, and its poor prognosis is related to its localisation and its capacity to relapse locally.

Malignant ectomesenchymoma of the cerebrum. Case report and discussion of therapeutic options.

UNLABELLED: Malignant ectomesenchymoma is a rare tumour that contains both ectodermal and mesenchymal elements. Only three patients with a manifestation in the cerebrum and clinicopathological data have been reported until now. We present a patient with an intracerebral ectomesenchymoma, review the literature and discuss currently available therapeutic options. In a 10-year-old girl, a left suprasellar temporo-parieto-occipitally localised tumour was diagnosed. The tumour was completely excised macroscopically in two surgical sessions. For the mesenchymal part of the tumour she subsequently underwent multidrug chemotherapy followed by radiation therapy. Considering the neuroectodermal element of the tumour, radiotherapy was applied to the craniospinal axis with a local boost. Therapy was tolerated well without any severe side effects. Six years from diagnosis, the patient is alive without a tumour relapse. CONCLUSION: Due to the sparcity of reported cases with malignant ectomesenchymoma, the role of adjuvant therapy is unclear. Multimodal therapy may be able to improve outcome.

Distinctive dermal clear cell mesenchymal neoplasm: clinicopathologic analysis of five cases.

Dermal clear cell tumors are not common. This group of lesions is comprised primarily of clear cell adnexal lesions, balloon cell melanocytic lesions, and metastatic clear cell carcinomas. We report the clinicopathologic features of five cases of a novel dermal clear cell neoplasm that appears mesenchymal in nature. The affected patients included 3 men and 2 women ranging in age from 38 to 70 (median, 45 years). All the lesions occurred on the lower limb. Clinically described as smooth cutaneous nodules, size ranged from 0.5 to 2.5 cm in greatest dimension and the lesions were present from weeks to 5 years prior to excision. Situated in the reticular dermis, the tumors usually extended to involve the subcutis with sparing of the papillary dermis. The tumors were composed of large optically clear cells with vesicular nuclei. The lesions entrapped adnexal structures and thin dermal collagen fibers. Mitoses were rare (less than 1 per 25 hpf). A single case showed more pleomorphic nuclei as well as quite frequent mitoses and was considered of uncertain biologic potential. Immunohistochemistry revealed reactivity only for NKI-C3 (5/5 cases), CD68 (2/5 cases), and vimentin (2/3 cases); melanocytic, epithelial, and lymphoid markers were uniformly negative. All five lesions were locally excised; the more pleomorphic and mitotically active lesion was widely re-excised and given subsequent radiation therapy. In follow-up ranging from 1.5 to 11 years (median, 5.5 years), none of these lesions has recurred. These tumors appear to be mesenchymal in nature, but their precise line of differentiation is unknown. Recognition of these lesions is important to avoid confusion with better-known malignant neoplasms.