Primitive Mesenchymal Tumor Research Articles

Embryonal rhabdomyosarcoma of oropharynx in a 65-year-old male with indolent clinical presentation and unusual morphology

Abstract Introduction/Objective Embryonal rhabdomyosarcoma (ERMS) is a malignant primitive mesenchymal tumor which commonly affects children and adolescence. Although head and neck area is a common location for ERMS, oropharynx is rarely involved. ERMS in adults often present with stage IV disease and show a relatively poor prognosis. Loss of heterozygosity in 11p15.5 is one of the common genetic findings in sporadic ERMS. Methods/Case Report A 65-year-old male with no significant medical history, presented with pharyngodynia and was found to have a polypoid mass originating from the pharyngeal surface of the soft palate and extends into the vallecula. He reported having this mass for a decade and having intermittent episodes of similar oropharyngeal symptoms which were usually resolved with antibiotics. Results (if a Case Study enter NA) Excisional biopsy shows a 2.4 cm polypoid mass with atypical cellular proliferation in submucosa. Tumor cells demonstrate ovoid to round nuclei and eosinophilic cytoplasm. No mitotic figure was found and Ki67 proliferation index was extremely low (<1%). Immunostains showed that the tumor cells are positive for Desmin and MyoD1. Scattered cells are positive for Myogenin. Due to the unusual clinical presentation and low proliferation activity, late onset of fetal rhabdomyoma was also considered in the differential diagnosis. The specimen was sent for chromosomal microarray which showed chromosomal gains and losses including loss of heterozygosity in chromosome 11. This finding together with cytologic atypia are mostly compatible with the diagnosis of ERMS. Post-biopsy MRI and PET-CT did not reveal any residual disease or distant metastasis. Patient has been followed up for 6 months after biopsy with no sign of recurrence. Conclusion Our case indicates that ERMS in adult can present with an indolent clinical process and low proliferating activity. Diagnosis can be challenging in this scenario. Chromosomal microarray is a useful tool to help confirm the diagnosis.

Genomic profiling identifies genes and pathways dysregulated by HEY1-NCOA2 fusion and shines a light on mesenchymal chondrosarcoma tumorigenesis.

Mesenchymal chondrosarcoma is a rare, high‐grade, primitive mesenchymal tumor. It accounts for around 2–10% of all chondrosarcomas and mainly affects adolescents and young adults. We previously described the HEY1–NCOA2 as a recurrent gene fusion in mesenchymal chondrosarcoma, an important breakthrough for characterizing this disease; however, little study had been done to characterize the fusion protein functionally, in large part due to a lack of suitable models for evaluating the impact of HEY1–NCOA2 expression in the appropriate cellular context. We used iPSC‐derived mesenchymal stem cells (iPSC‐MSCs), which can differentiate into chondrocytes, and generated stable transduced iPSC‐MSCs with inducible expression of HEY1–NCOA2 fusion protein, wildtype HEY1 or wildtype NCOA2. We next comprehensively analyzed both the DNA binding properties and transcriptional impact of HEY1–NCOA2 expression by integrating genome‐wide chromatin immunoprecipitation sequencing (ChIP‐seq) and expression profiling (RNA‐seq). We demonstrated that HEY1–NCOA2 fusion protein preferentially binds to promoter regions of canonical HEY1 targets, resulting in transactivation of HEY1 targets, and significantly enhances cell proliferation. Intriguingly, we identified that both PDGFB and PDGFRA were directly targeted and upregulated by HEY1‐NCOA2; and the fusion protein, but not wildtype HEY1 or NCOA2, dramatically increased the level of phospho‐AKT (Ser473). Our findings provide a rationale for exploring PDGF/PI3K/AKT inhibition in treating mesenchymal chondrosarcoma. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Primitive myxoid mesenchymal tumor of infancy: Case report and review of the literature

Primitive myxoid mesenchymal tumor of infancy (PMMTI) is an extremely rare soft tissue tumor with only a few cases. Herein, we report a case of 5-months-old girl presenting with a soft tissue mass on the sole of the left foot that recurred 2months after a first resection. The Doppler ultrasound imaging showed abundant blood flow in the tumor. Magnetic resonance imaging (MRI) showed a well demarcated tumor on the sole of the left foot. The surgically resected tumor consisted of primitive mesenchymal tumor cells dispersed in a myxoid background with delicate small blood vessels. Immunohistochemically, tumor cells expressed vimentin but were negative for AE1/AE3, Desmin, Muscle-Specific Actin, MyoD1, Myogenin, CD34, S-100 protein and CD99. Fluorescence in situ hybridization (FISH) showed absence of chromosomal translocation involving SYT and ETV6. Thus, the patient was diagnosed with a primitive myxoid mesenchymal tumor of infancy. To our knowledge, this is the first case of PMMTI affecting the sole of the foot.

Extraskeletal mesenchymal chondrosarcoma mimicking a thrombosed venous aneurysm with femoral vein involvement: A case report

Abstract Introduction/Objective Mesenchymal chondrosarcoma is a high-grade primitive mesenchymal tumor, which accounts for <5% of all chondrosarcomas and commonly affects young adults (peak incidence in second to third decade of life). The tumor has a widespread anatomic distribution, frequently involving the craniofacial bones as well as extraskeletal sites. The clinical presentation of an inguinal mass mimicking a thrombosed venous aneurysm is unusual and represents a potential diagnostic pitfall. Methods/Case Report A 42-year-old female with hypertension and obesity initially presented with a two-week history of left lower leg swelling. Venous doppler revealed presumed venous thrombosis, and she was prescribed apixaban while no history of coagulopathy, immobility, or recent surgery was noted. Two months later, she had residual swelling. Follow-up CT scan favored a large, peripherally thrombosed venous aneurysm arising from the left common femoral vein, while MRI showed a lobulated, inguinal soft tissue mass abutting the vein. Biopsy of the mass demonstrated a spindle cell mesenchymal neoplasm; subsequent resection revealed a pink-to-tan, well-circumscribed, and encapsulated mass (5.2 cm) with focal left common femoral vein invasion. Microscopically, the lesion demonstrated poorly-differentiated, oval-to-spindle cells with prominent staghorn vasculature interspersed were focal areas of well-differentiated hyaline cartilage. Immunohistochemical stains showed that the lesional cells were negative for cytokeratin cocktail, EMA, SMA, desmin, S100 protein, SOX10, STAT6, MUC4, MDM2, and ER. Next-generation sequencing (NGS) revealed a HEY1-NCOA2 gene fusion, confirming the diagnosis of extraskeletal mesenchymal chondrosarcoma. Results (if a Case Study enter NA) N/A Conclusion Extraskeletal mesenchymal chondrosarcoma can rarely present as an inguinal soft tissue mass with vascular invasion, mimicking a thrombosed venous aneurysm. Molecular confirmation of HEY1-NCOA2 gene fusion can help confirm the diagnosis in unusual clinical presentations.

Embryonal rhabdomyosarcoma of liver in a 16-year-old boy: A rare case report

Introduction: Primitive mesenchymal tumors represent about 9–15% of all hepatic tumors in children. Only about 150 cases have been reported in literature so far. Herein, we report a case of ruptured embryonal rhabdomyosarcoma. case report: A 16-year-old boy, with weight of 26 kg, presented to us with sudden onset of abdominal pain and fever. clinical examination revealed a tender hepatomegaly about 6 cm below right costal margin. contrast-enhanced computed tomography scan of abdomen revealed 15x11x9 cm heterogenous multi-septated loculated mass lesion involving right lobe of liver involving segments 5, 6, 7, 8. Diagnostic laparoscopy showed a tumor occupying the entire right lobe of liver with no other deposits. the tumor capsule was

Primitive myxoid mesenchymal tumor of infancy: Report of two cases and review of the literature

Primitive myxoid mesenchymal tumor of infancy is a recently recognized soft tissue tumor with only a few cases reported. Here, we reported another two cases of the lesion, a 5-month-old boy presenting with a soft tissue mass in the neck region that recurred 2 months later and a 3-day-old girl with a congenital superficial dorsal lumbar mass that extended to the spinal canal 1 month later. They shared similar histological patterns, such as unusual diffuse myxoid background, delicate vascular network, small cystic spaces, low to moderate cellularity, and primitive mesenchymal tumor cells. Immunohistochemically, the tumor cells showed positive for vimentin, CD99, CD117 and nestin, negative for myoid, lipoblastic, histiocytic, and neural markers. In conclusion, primitive myxoid mesenchymal tumor of infancy is a distinctive entity with its own clinical pathological features. Expression of CD99, CD117 and nestin may be consistent with the primitive nature of the tumor and may serve as ancillary markers for differential diagnosis from the other infantile tumors.

A case of unclassified type, borderline sex cord-stromal cell tumor arising in ectopic ovarian tissue

Sex cord-stromal cell tumors of ovary is derived from the coelomic epithelium or mesenchymal cells of the embryonic gonads and unclassified type of them consists of 0.5-0.8% of all malignant ovarian tumors. Histologic findings and management of a 37-year-old woman with sex cord-stromal tumor, unclassified type, were described. We ruled out soft tissue tumors that usually originate from the retroperitoneum, and with immunohistochemical staining, this tumor was diagnosed as a retroperitoneal unclassified borderline sex cord-stromal cell tumor. She had a normal postoperative course, and was discharged 14 days postoperatively. Unclassified sex cord-stromal cell tumor of ovary is rare and should be discriminated between other tumors, such as primitive mesenchymal tumor and metastatic endometrial cancer.

Undifferentiated sarcoma: does it exist? A clinicopathologic study of 7 pediatric cases and review of literature

Undifferentiated sarcomas are primitive mesenchymal tumors that cannot be classified among standardized histopathologic entities. Whether they represent a homogeneous group with common histogenesis and clinical behavior or comprise a variety of tumors able to differentiate along specific maturative lineages is still debated. To identify prognostic and histogenetic markers, we analyzed 7 undifferentiated sarcomas (4 in the trunk and 3 in the extremities). Mean patient age was 7.5 years, and mean follow-up was 18 months. Two clinicopathologic subtypes emerged from this study. Four primitive mesenchymal undifferentiated sarcomas arose mainly on the trunk and very proximal extremities, had an aggressive clinical course with poor outcome (3 deaths from disease, 1 with persistent disease), and displayed sheets of oval cells, with bland nuclei. Three spindle cell undifferentiated sarcomas arose on the extremities, had a favorable outcome, and showed elongated spindle cells with areas of primitive fibrosarcoma. All were negative for epithelial membrane antigen, cytokeratins, CD34, smooth muscle actin, desmin,Myf4, and HMB45 and showed nuclear staining for INI. Focal staining for S100 and CD99 was found in 3 and 4, respectively. Among stem cell markers, CD117 was positive in 3 cases (1 primitive, 2 spindle), nestin in 5 cases (4 primitive, 1 spindle), and CD105-stained tumor cells lining newly formed vascular spaces in 4 cases (1 primitive, 3 spindle). Survivin was weakly expressed in 6 cases and reflected low levels of mRNA (median survivin/GAPDH ratio, 1.096). Cytogenetic analysis revealed nonspecific translocations in 3 tumors. No translocations associated with Ewing sarcoma, synovial sarcoma, or alveolar rhabdomyosarcoma were found. In summary, primitive undifferentiated sarcomas occur in the trunk, behave aggressively, and express nestin. Spindle cell undifferentiated sarcomas occur in extremities, have a favorable outcome, resemble fibrosarcomas, and have similarly low survivin levels and display CD105-positive vascular spaces, which may represent an early hemangiopericytomatous pattern.

Early detection of adrenocortical carcinoma in a child with Li–Fraumeni syndrome

We report an early detection of cancer in a child with Li-Fraumeni syndrome. The proband was a 3-year-old male with a primitive mesenchymal tumor. Genetic analysis showed a germline TP53 mutation in codon 220 exon 6, which changed TAT --> TGT and resulted in a tyrosine-to-cysteine amino acid substitution (Tyr220Cys). The younger sister at risk was followed, and an asymptomatic adrenal cortical carcinoma was detected 3 years later. The report highlights the importance of genetic counseling and provides an example of early detection of cancers in childhood LFS carriers.

Tumors associated with oncogenic osteomalacia express genes important in bone and mineral metabolism.

Oncogenic osteomalacia (OOM) is associated with primitive mesenchymal tumors that secrete phosphaturic factors resulting in low serum concentrations of phosphate and calcitriol, phosphaturia, and defective bone mineralization. To identify overexpressed genes in these tumors, we compared gene expression profiles of tumors resected from patients with OOM and histologically similar control tumors using serial analysis of gene expression (SAGE). Three hundred and sixty-four genes were expressed at least twofold greater in OOM tumors compared with control tumors. A subset of 67 highly expressed genes underwent validation with an extended set of OOM and control tumors using array analysis or reverse-transcription polymerase chain reaction (RT-PCR). Ten of these validated genes were consistently overexpressed in all OOM tumors relative to control tumors. Strikingly, genes with roles in bone matrix formation, mineral ion transport, and bone mineralization were highly expressed in the OOM tumors.

Immunophenotype, proliferation, DNA ploidy, and biological behavior of gastrointestinal stromal tumors: A multivariate clinicopathologic study

To determine the prognostic impact of clinical, immunohistochemical, and biological parameters, we examined 52 gastrointestinal stromal tumors (GIST) by conventional light microscopy and immunohistochemistry. DNA ploidy was analyzed by image cytometry on cytospin preparation. The proliferative activity was determined by mitosis counting and assessment of Ki-67 reactivity by means of monoclonal antibody Ki-S5. A histopathologic grade was assigned to each tumor according to the French Federation of Cancer Centers (FNCLCC) grading system. Next to vimentin, CD34 was the most prevalent antigen, followed by markers of neural and muscular differentiation. Many tumors exhibited a mixed phenotype. Twenty-one tumors were diploid, eight hypodiploid, and 23 aneuploid. In univariate analysis, tumor grade, Ki-S5 labeling index, mitotic count, atypical mitoses, cellularity, and sex were predictive of both mortality and metastasis risk. DNA ploidy only correlated with overall survival, whereas the tumor location affected the occurrence of metastases. Multivariate analysis selected Ki-S5 scores ( P < .0001) and atypical mitoses ( P = .012) as independent prognosticators for overall survival, and tumor grade ( P = .0036) and size ( P = .0055) as predictors of metastatic spread. We conclude that GIST are primitive mesenchymal tumors capable of divergent differentiation, which does not influence their prognosis. The latter appears to be best predicted by histopathologic grading and the Ki-67 labeling index.

Malignant Fibrous Histiocytoma of the Kidney

Malignant fibrous histiocytoma is a primitive mesenchymal tumor which seldom occurs in the genitourinary organs. Despite radical operation, prognosis is generally poor and seems not to be improved by chemotherapy or radiotherapy. We present a case of a malignant fibrous histiocytoma of the renal capsule. The tumor could be removed totally and no signs of metastases were found. Eight months later the patient was readmitted with recurrence of tumor and widespread metastases.

Budd-Chiari syndrome caused by undifferentiated small round cell tumor of the liver in an adult

An undifferentiated small round cell tumor of the liver in a 60 year old black male is described. Although the light microscopic findings in this tumor were strongly suggestive of embryonal rhabdomyosarcoma, the ultrastructural study disclosed no myofibrils or other specific characteristics. Thus, we classify this tumor as an embryonic tumor or primitive mesenchymal tumor of the liver.