Rhabdomyosarcomatous Component Research Articles

Teratoma-associated and so-called pure Wilms tumour of the ovary represent two separate tumour types with distinct molecular features.

Ovarian Wilms tumour (WT)/nephroblastoma is an extremely rare neoplasm that has been reported to occur in pure form or as a component of a teratomatous neoplasm. We hypothesized that teratoma-associated and pure ovarian WT may represent different tumour types with diverging molecular backgrounds. To test this hypothesis, we comprehensively characterized a series of five tumours originally diagnosed as ovarian WT. The five cases comprised three teratoma-associated (two mature and one immature) and two pure WTs. Two of the teratoma-associated WTs consisted of small nodular arrangements of "glandular"/epithelial structures, while the third consisted of both an epithelial and a diffuse spindle cell/blastemal component. The pure WTs consisted of "glandular" structures, which were positive for sex cord markers (including inhibin and SF1) together with a rhabdomyosarcomatous component. The two pure WTs harboured DICER1 pathogenic variants (PVs), while the three associated with teratomas were DICER1 wildtype. Panel-based DNA sequencing of four of the cases did not identify PVs in the other genes investigated. Analysis of the HA19/IGF2 imprinting region showed retention of imprinting in the pure WTs but loss of heterozygosity with hypomethylation of the ICR1 region in two of three teratoma-associated WTs. Furthermore, copy number variation and clustering-based whole-genome DNA methylation analyses identified divergent molecular profiles for pure and teratoma-associated WTs. Based on the morphological features, immunophenotype, and molecular findings (DICER1 PVs, copy number, and DNA methylation profiles), we suggest that the two cases diagnosed as pure primary ovarian WT represent moderately to poorly differentiated Sertoli Leydig cell tumours (SLCTs), while the tumours arising in teratomas represent true WTs. It is possible that at least some prior cases reported as pure primary ovarian WT represent SLCTs.

A Case of Ovarian Sertoli-Leydig Cell Tumor With Rhabdomyosarcomatous Component Presented With Tumor Rupture

A Case of Ovarian Sertoli-Leydig Cell Tumor With Rhabdomyosarcomatous Component Presented With Tumor Rupture

Hepatic carcinosarcoma with rhabdomyosarcoma: A case report and review of literature

Objective To analyze the clinical and pathological manifestations of a hepatic carcinosarcoma case with rhabdomyosarcoma components (HCSR).Methods A case of HCSR was observed by macroscopy, microscopy, immunohistochemistry and electron microscopy, along with thorough review of correlated literatures.Results The tumor tends to occur in elder patients without differences on gender. Epigarstric sicknesses, AFP rising in serum, and a mass on the right liver shown in radiography are commonly initial signs. It was composed of both hepatic carcinoma and variously differentiated sarcoma components, with identifiable rhabdomyosarcoma. Immunohistochemistry showed that the hepatic carcinosarcoma was positive of epithelial markers and mesenchymatous component was diffuse positive of Vimentin, and mosaic positive of SDHB, CD117, while rhabdomyosarcoma was positive of muscular markers. Transmission electron microscopy showed the tumor had both epithelial and rhabdomyosarcoma ultra-microstructure.Conclusion HCSR is a very rare type and highly malignant tumor with a dismal prognosis, hardly demonstrating unique clinical manifestations. Diagnosis and differential diagnosis rely on combination of histomorphology, immunohistochemistry and ultra-microstructure observation.

Early-stage multi-differentiated gastric carcinosarcoma and post-resection local recurrence: a case report

BackgroundCarcinosarcoma is a rare neoplasm with a poor prognosis that is most often discovered at an advanced stage; a gastric carcinosarcoma is even rarer than carcinosarcomas originating in other organs, such as the uterus. We report our experience with an early-stage multi-differentiated gastric carcinosarcoma.Case presentationA 68-year-old male patient presented with anemia, and his fecal occult blood test was positive. An endoscopic examination was conducted which revealed a hemorrhagic, irregular, protruding lesion in the stomach. The lesion was diagnosed as an adenocarcinoma by histopathological examination of the biopsy specimen, and a segmental gastrectomy was performed. A 41 × 29 × 18 mm3 protruding lesion was observed in the resection specimen, and histologically confirmed to be a gastric carcinosarcoma with mixed adenocarcinomatous and sarcomatous composition. Tumor invasion was limited to the submucosa. Besides the adenocarcinomatous portion, neuroendocrine differentiation and AFP-positive gastric carcinoma were present in the carcinomatous portion of the tumor; in the sarcomatous portion, chondrosarcomatous, leiomyosarcomatous, and rhabdomyosarcomatous components were observed in addition to the undifferentiated sarcomatous component. Furthermore, the tumor included SALL4-positive germ cell-like cells. Despite early-stage detection, the cancer recurred locally 14 months after tumor resection, which necessitated a total gastrectomy. At the 2-month follow-up after the total gastrectomy, the patient was alive. This patient had developed an esophageal squamous cell carcinoma and primary lung adenosquamous carcinoma, both of which were resected.ConclusionsFew cases of early-stage gastric carcinosarcoma have been reported, but there are no reports of recurrence to date. Local recurrence as in this patient, and even in early-stage cases, requires cautious surveillance to check for post-resection recurrence and metastasis. The etiopathogenesis of carcinosarcoma has not yet been elucidated; however, in the present case, despite the tumor’s relatively small size, it exhibited various types of differentiation in both the carcinomatous and sarcomatous components and a proliferative germ cell-like portion, which suggests that the monoclonal origin hypothesis may be a valid theory for the carcinosarcoma.

Sarcomatoid urothelial bladder carcinoma in adults: Histology, symptomatology, treatments and survival

ObjectiveSarcomatoid urothelial bladder carcinoma comprises 3% of the tumours of the bladder and is considered one of the most aggressive tumours of the urinary tract. Our aim is to analyze the characteristics of sarcomatoid urothelial bladder carcinoma in adults, its treatments and survival. MethodA retrospective study performed between 2000 and 2017 of all the patients with a sarcomatoid urothelial bladder carcinoma in a single centre. We studied the anatomopathological characteristics, symptoms at time of diagnosis, treatment given and survival according to the treatment given. ResultsSixteen patients were diagnosed with sarcomatoid carcinoma, 11 with no heterologous component, one with rhabdomyosarcomatous components, 2 with chondrosarcomatous components and 2 with osteosarcomatous components. The mean age was 74 years (±20) and 88% were smokers. The primary symptom was haematuria, and the least well-tolerated was dysuria together with hypogastric pain. Ninety-four percent of the patients had muscle layer infiltration and 18% had metastases at the time of diagnosis. Thirty-seven percent of the patients were treated by radical cystectomy, thirteen percent by radical cystectomy plus adjuvant chemotherapy, and 50% were treated by palliative transurethral resection to control their symptoms. A survival curve was made with the different treatments given, which showed a mean global survival of 7 months and no statistically significant differences in terms of survival according to the treatment given. ConclusionsSarcomatoid urothelial carcinoma is an aggressive disease, of rapid and torpid onset which occurs in patients of advanced age and smokers. There are no established treatment guidelines, and it appears that no treatment influences increased survival. Cystectomy should be evaluated as a treatment alternative for patients whose symptoms are difficult to control. The various heterologous components do not appear to influence the progression of the disease or patient survival.

Immature Gastric Teratoma with Rhabdomyosarcomatous and Primitive Neuroectodermal Tumor Components in an Adult Patient: A Case Report

Immature Gastric Teratoma with Rhabdomyosarcomatous and Primitive Neuroectodermal Tumor Components in an Adult Patient: A Case Report

SATB2 Expression Is Sensitive but Not Specific for Osteosarcomatous Components of Gynecologic Tract Carcinosarcomas: A Clinicopathologic Study of 60 Cases.

The novel marker special AT-rich sequence binding protein (SATB2) is highly sensitive for mesenchymal tumors with osteoblastic differentiation. However, SATB2 expression in gynecologic tract carcinosarcoma has not been previously explored. Given the potential prognostic and therapeutic implications of heterologous carcinosarcoma in the gynecologic tract, this study investigates the utility of SATB2 in identifying osteosarcomatous elements. A multi-institution database review identified consecutive cases of gynecologic tract carcinosarcoma including both heterologous and homologous types. Clinicopathologic parameters were recorded. Nuclear SATB2 immunoreactivity was scored from 1 representative whole-slide section from each case. Sixty gynecologic tract carcinosarcoma were identified (uterine corpus=47, ovary=11, fallopian tube=1, cervix=1) including 32 heterologous type (7 osteosarcoma, 3 mixed osteosarcoma/chondrosarcoma, 6 chondrosarcoma, 12 rhabdomyosarcoma, 4 mixed chondrosarcoma/rhabdomyosarcoma) and 28 homologous type. Patient ages ranged from 41 to 90 yr (average 67.9 yr). Mostly diffuse strong SATB2 positivity was present in 10/10 (100%) cases containing osteosarcoma. In these cases, SATB2 positivity was seen in malignant cells intimately associated with osteoid or bone [3/10 (30%) of these cases additionally showed patchy weak/moderate SATB2 staining in areas of nonosteogenic sarcoma elsewhere in the same tumor]. SATB2 positivity was present in 30/50 (60%) cases lacking osteosarcoma, predominantly as patchy moderate staining within undifferentiated sarcoma. No cases showed SATB2 positivity in chondrosarcoma or rhabdomyosarcoma components. SATB2 is a highly sensitive marker for osteosarcomatous differentiation in gynecologic tract carcinosarcoma, and is also highly specific when used to differentiate osteosarcoma from chondrosarcoma and rhabdomyosarcoma elements in these tumors. However, a positive SATB2 result may lack specificity for differentiating osteosarcoma from an undifferentiated sarcoma component.

DICER1 hotspot mutations in ovarian Sertoli-Leydig cell tumors: a potential association with androgenic effects

Sertoli-Leydig cell tumors (SLCTs) are representative of androgenic ovarian tumors, and they show diverse histologic differentiation, including heterologous differentiation. Genetically, SLCTs are characterized by the presence of DICER1 mutations. In the present study, we analyzed the correlation between somatic DICER1 hotspot mutations and clinicopathological features in 10 ovarian SLCTs. Six of the 10 (60%) SLCTs harbored a DICER1 hotspot mutation. Five of the 6 DICER1-mutated SLCT patients showed androgenic manifestations, including amenorrhea and hirsutism, and 4 of the 6 were associated with the significant elevation of serum testosterone. In contrast, none of the 4 DICER1 wild-type SLCT patients showed virilization. The patient age at diagnosis was lower in those with DICER1-mutated SLCTs (average, 24.7; range, 17-43) than in those with DICER1 wild-type tumors (average, 64.8; range, 47-77). Histologically, heterologous differentiation was found in 4 SLCTs, all of which were DICER1 mutant. Heterologous components included gastrointestinal-type mucinous epithelium (n=3), carcinoid (n=1), and rhabdomyosarcoma (n=1). In the latter, the rhabdomyosarcomatous component was dominant to the SLCT component. In summary, DICER1 hotspot mutations are closely associated with androgenic effects in ovarian SLCTs. It is suggested that DICER1 mutations are involved in the dysregulation of sex hormone synthesis in SLCT patients. Somatic DICER1 hotspot mutations are more common in SLCT patients during the reproductive years than in those during the postreproductive years. DICER1 hotspot mutations may support the pathological diagnosis of SLCTs in cases wherein the heterologous component overwhelms and masks the SLCT component.

Loss of CDKN2A Promoter Methylation Coincides With the Epigenetic Transdifferentiation of Uterine Myosarcomatous Cells.

Leiomyosarcoma is the most common type of uterine sarcoma and usually displays typical morphology. Heterologous leiomyosarcoma is the rarest variant, in which the tumor contains liposarcomatous, osteosarcomatous, or rhabdomyosarcomatous components. We have investigated the largest series of uterine leiomyosarcoma with a rhabdomyosarcomatous component and we have disclosed a molecular finding, which coincides to the process of transdifferentiation from smooth muscle into striated muscle phenotype. The surgical specimens of 5 rare cases of uterine leiomyosarcoma with a rhabdomyosarcomatous component were formalin fixed and paraffin embedded. In addition to hematoxylin/eosin stains, phosphotungstic acid hematoxylin staining, immunohistochemistry, and methylation-specific polymerase chain reaction the CDKN2A promoter region were performed. Leiomyosarcomatous cells were found to be strongly immunoreactive for both desmin and α-smooth muscle actin. Rhabdomyosarcomatous cells were immunoreactive for sarcomeric actin, desmin, vimentin, CD10, and p16. The methylation-specific polymerase chain reaction revealed the presence of a methylated allele and an unmethylated allele in the microdissected samples, coming from leiomyosarcomatous cells. On the contrary, 2 unmethylated alleles, molecular expression of a loss of heterozygosity, were detected in all the microdissected samples in the rhabdomyosarcomatous cells. The loss of heterozygosity methylation in the promoter region of the CDKN2A gene, occurred only in the rhabdomyosarcomatous cells with increases in both p16 and p14 expression. This event may result in an inhibition of cdk4/cdk6 activity, stabilizes the tumor suppressor protein p53, and coincides with the transdifferentiation from smooth muscle into striated muscle.

A survey of DICER1 hotspot mutations in ovarian and testicular sex cord-stromal tumors

Sertoli–Leydig cell tumors are characterized by the presence of somatic DICER1 hotspot mutations. In this study, we sought to define the association between DICER1 hotspot mutations and different morphologic subtypes of ovarian Sertoli–Leydig cell tumors. Furthermore, we aimed to assess whether DICER1 hotspot mutations occur in other ovarian sex cord-stromal tumors, testicular sex cord-stromal tumors, or other female genital tract tumors with rhabdomyosarcomatous differentiation. We subjected a series of ovarian Sertoli–Leydig cell tumors (n=32), Sertoli cell tumors (n=5) and gynandroblastomas (n=5), testicular sex cord-stromal tumors (n=15) and a diverse group of female genital tract tumors with rhabdomyosarcomatous morphology (n=10) to DICER1 hotspot mutation analysis using Sanger sequencing. We also tested two gynandroblastomas for the presence of FOXL2 hotspot mutations (p.C134W; c.402C>G). Twenty of 32 (63%) Sertoli–Leydig cell tumors harbored a DICER1 hotspot mutation, of which 80% had the p.E1705K mutation. No association was found between DICER1 mutation status and the presence of heterologous or retiform differentiation in Sertoli–Leydig cell tumors. DICER1 mutations were found at similar frequencies in gynandroblastoma (2/5; 40%) and ovarian Sertoli cell tumors (5/8; 63%; P>0.1), and all mutated tumors harbored a p.E1705K mutation. DICER1 hotspot mutations were also identified in a single cervical rhabdomyosarcoma and in the rhabdomyosarcomatous component of a uterine carcinosarcoma. No DICER1 mutations were detected in testicular sex cord-stromal tumors. Two DICER1 wild-type gynandroblastomas harbored a p.C134W FOXL2 hotspot mutation in both tumor components. In this study we confirmed that DICER1 hotspot mutations occur in over half of ovarian Sertoli–Leydig cell tumors, and are unrelated to tumor differentiation. We also widened the spectrum of ovarian sex cord-stromal tumors with sertoliform differentiation, in which DICER1 mutations are known to occur, to include Sertoli cell tumors and gynandroblastomas. Our results suggest that DICER1 mutations may not have a role in testicular sex cord-stromal tumorigenesis.

Rhabdomyosarcoma with Pseudolipoblasts Arising in Ovarian Carcinosarcoma: A Distinctive Postchemotherapy Morphologic Variant Mimicking Pleomorphic Liposarcoma

We describe a case of ovarian carcinosarcoma occurring in a 60-year-old female. The neoplasm was excised after neoadjuvant chemotherapy and contained a predominant heterologous pleomorphic rhabdomyosarcomatous component in which there were numerous multivacuolated rhabdomyoblasts that strongly mimicked lipoblasts. The clear cell variant of rhabdomyosarcoma is rarely documented, but this case shows a highly unusual finding in which the rhabdomyoblasts show the prominent multivacuolation with nuclear indentation characteristic of and indistinguishable from pleomorphic lipoblasts. This appears to represent a posttreatment phenomenon. As this finding might conceivably occur in other rhabdomyosarcomas after chemotherapy, we highlight the potential for diagnostic confusion with pleomorphic liposarcoma, which is usually diagnosed by morphology so that immunohistochemistry for muscle markers might not be performed.

Malignant Müllerian Mixed Tumor of the Uterine Cervix with a Small Cell Neuroendocrine Carcinoma Component

Malignant Müllerian mixed tumors (MMMTs) of the uterine cervix are extremely rare, accounting for 0.005% of all cervical malignancies. To date, only approximately 50 well-documented cases have been reported. Although several epithelial components have been described in cervical MMMTs, small cell neuroendocrine carcinoma (SCC) has not appeared in the English literature. We present a 43-year-old woman, para 2 gravida 2, who had MMMT with SCC and rhabdomyosarcoma components in the uterine cervix. She was referred to our hospital because of a cervical mass with an abnormal Pap smear result. Cervical biopsy revealed SCC. After neoadjuvant chemotherapy with balloon-occluded arterial infusion, she underwent type II radical hysterectomy with pelvic lymphadenectomy. Histological analysis revealed that the cervical tumor comprised SCC and rhabdomyosarcoma components. Genotype analysis indicated human papillomavirus type 18. She underwent concurrent chemoradiation therapy. The patient had been free of the disease and showed no evidence of recurrence 38 months after operation.

横紋筋肉腫と小細胞癌よりなる胃癌肉腫の1例

横紋筋肉腫と小細胞癌よりなる胃癌肉腫の1例

Composite uterine neoplasm with embryonal rhabdomyosarcoma and primitive neuroectodermal tumor components: rhabdomyosarcoma with divergent differentiation, variant of primitive neuroectodermal tumor, or unique entity?

Three cases of composite uterine neoplasms comprised of primitive neuroectodermal tumor (PNET) and rhabdomyosarcoma (RMS) have previously been described, including only one wherein the rhabdomyosarcomatous component was of the embryonal subtype. Whether such composite neoplasms are a variant of RMS, a variant of PNET, or a unique entity is unknown. We report the clinicopathologic, immunohistochemical, and molecular cytogenetic findings in a case of uterine embryonal RMS with coexisting PNET that was diagnosed in a 25-year-old female. The tumor broadly involved the cervix and corpus uteri and resulted in uterine inversion. The 2 distinct components each showed classic morphologic features, including cartilage in the RMS component. The unique combination of histologic, immunohistochemical and molecular findings in composite neoplasms of this type raises a question of whether they should be classified and treated as RMS, PNET, or a unique high-grade sarcoma. A variety of clinicopathologic arguments are presented that support the notion that the current neoplasm is an embryonal rhabdomyosarcoma with divergent neuroectodermal and cartilaginous differentiation.

Pulmonary carcinosarcoma successfully resected using the rib-cross thoracotomy approach: report of a case

Pulmonary carcinosarcoma is extremely rare and disease prognosis is very poor. A solid large tumor occupying the left thorax was detected in a 66-year-old female. Rib-cross thoracotomy was performed to excise the tumor; the 5th and 6th ribs and intercostal muscles and vessels were cut along the mid-axillary line, and the thorax was entered posteriorly at the 4th intercostal space and anteriorly at the 6th intercostal space, providing wide exposure of the entire thorax. Left pneumonectomy combined with chest wall resection was successfully performed, followed by chest reconstruction to achieve complete resection. Histopathologically, adenocarcinoma and spindle cell sarcoma containing rhabdomyosarcoma components were identified; the patient was diagnosed with pT3N1M0 stage IIIA true pulmonary carcinosarcoma. Postoperative adjuvant chemotherapy containing cisplatin and vinorelbine was administered. There was no recurrence of the disease 20months after surgery. Aggressive excision may result in favorable outcomes for pulmonary carcinosarcoma.

Oncocytic Adrenal Cortical Carcinosarcoma With Pleomorphic Rhabdomyosarcomatous Metastases

Adrenal cortical carcinosarcoma is a rare variant of adrenal cortical carcinoma. Sarcomatous change in adrenal cortical carcinomas is exceptionally rare, with only 9 cases previously described. Adrenal cortical carcinosarcomas tend to be aggressive tumors, with locoregional recurrence and rapid metastases from the sarcomatoid component. We describe what seems to be the first case of sarcoma arising in oncocytic adrenal cortical carcinoma. The sarcomatous component here was pleomorphic rhabdomyosarcoma. This occurred in a 45-year-old man who had nodal and pulmonary metastases of the rhabdomyosarcomatous component at presentation and who died of progressive disease 11 months later. Here, we discuss the clinical, radiologic, and pathologic findings and review the literature on adrenal cortical carcinosarcomas.

Ovarian germ cell tumors with rhabdomyosarcomatous components and later development of growing teratoma syndrome: a case report

IntroductionDevelopment of a sarcomatous component in a germ cell tumor is an uncommon phenomenon. Most cases reported have a grim prognosis. Growing teratoma syndrome is also an uncommon phenomenon and occurs in approximately 2% to 7% of non seminomatous germ cell tumors and should be treated surgically.Case presentationWe report the case of a 12-year-old Asian girl with an ovarian mixed germ cell tumor containing a rhabdomyosarcomatous component. She was treated with a germ cell tumor chemotherapy regimen and rhabdomyosarcoma-specific chemotherapy. Towards the end of her treatment, she developed a retroperitoneal mass that was increasing in size. It was completely resected, revealing a mature teratoma, consistent with growing teratoma syndrome. She is still in complete remission approximately three years after presentation.ConclusionThe presence of rhabdomyosarcoma in a germ cell tumor should be treated by a combined chemotherapy regimen (for germ cell tumor and rhabdomyosarcoma). In addition, development of a mass during or after therapy with normal serum markers should raise the possibility of growing teratoma syndrome that should be treated surgically.

Squamotous-type sarcomatoid carcinoma of the lung with rhabdomyosarcomatous components

Lung carcinosarcoma is an infrequently biphasic tumor composed of carcinomatous and sarcomatous components. It is divided into endobronchial (squamous-type) and peripheral (glandular type) categories. The carcinomatous component is usually a squamous carcinoma, and the sarcomatous component usually resembles a fibrosarcoma or a malignant fibrous histiocytoma. The presence of rhabdomyoblastic differentiation in such neoplasms is exceedingly rare. There are strong associations with smoking and asbestosis. In this study, we describe a unique case of a 43-year-old man with a 75 packet/year smoking history in whom a rare mixed malignant tumor of the lung was diagnosed and treated by left pneumonectomy. Histological examination of the resected specimen showed squamous cell carcinoma and rhabdomyosarcoma components. Although rare, the association of a sarcomatoid carcinoma of the lung with squamous cell carcinoma and rhabdomyosarcomatous component is possible and should be kept in mind when dealing with these unusual tumors.

Rhabdomyosarcomatous differentiation in a spermatocytic seminoma with review of literature

The sarcomatous differentiation occurring in spermatocytic seminoma (SS) renders an aggressive behavior with metastatic potential to this relatively indolent neoplasm. Correct identification of this sarcomatous component is essential as further management differs. Herein, we report a case of young male with SS with rapid increase in size of the tumor. Histopathology revealed a rhabdomyosarcomatous component infiltrating the rete-testis and epididymis along with a well-circumscribed SS.

Supplement 2, Proceedings of the 14th World Conference on Lung Cancer, Book 2

Supplement 2, Proceedings of the 14th World Conference on Lung Cancer, Book 2