Breast Metastasis of Extraskeletal Myxoid Chondrosarcoma: A Case Report

Background: Extraskeletal myxoid chondrosarcomas (EMCs) are rare mesenchymal neoplasms comprising approx. 3% of all soft tissue tumors. EMCs arise mainly from the deep soft tissues of the extremities, accompanied with high rates of recurrence and metastases. The molecular hallmarks of EMCs are various cytogenetic NR4A3 rearrangements, generating chimeric -NR4A3 proteins. The most common reciprocal translocation t(9;22)(q22;q12), results in a fusion of the EWS RNA-binding protein 1 gene (EWSR1) to the nuclear receptor subfamily 4, group A, member 3 gene (NR4A3 or TEC; approximately 75% of cases). Further cytogenetic t(9;17)(q22;q11) rearrangements involve TAF15 RNA polymerase II, TATA box binding protein (TBP)-associated factor (TAF15; approximately 15% of cases). The less frequent reciprocal translocations t(9;15)(q22;q21) and t(9;3)(q22;q12), result in transcription factor 12 (TCF12)-NR4A3 and TRK-fused gene (TFG)-NR4A3 fusion proteins. Although the oncogenic -NR4A3 fusion transcripts seem to have a crucial role in EMC tumorigenesis and progression, the specific biological function and the mechanism of action remain to be defined. Methods: We characterized the cytogenetic rearrangements of 25 comprehensive EMC tumors by RT-PCR and/or fluorescence in situ hybridization (FISH). Next generation sequencing (NGS) was performed (Illumina MiSeq platform) to reveal additional genetic alterations besides the known chromosomal translocation. Therefore, a comprehensive cancer panel was designed, comprising 27 cancer-related genes known to be frequently mutated across various malignancies. Results: Overall, fusion transcripts were detected in 22 of 25 samples (88%). Sixteen were positive for the EWSR1-NR4A3 and six for the TAF15-NR4A3 fusion gene. The t(9;15) and t(9;3) translocations, resulting in TCF12-NR4A3 and TFG-NR4A3 fusion proteins were not identified in any EMC case. In Addition, several known oncogenic mutations were detected which have not been previously reported in EMC. Conclusions: The combination of RT-PCR and FISH on paraffin-embedded tissue is a sensitive and specific method for the molecular detection of the pathogenic translocations to be applied in the differential diagnosis of extraskeletal myxoid chondrosarcomas. Our results emphasize that cytogenetic NR4A3 rearrangements are the initiating events in the pathogenesis of EMC. Furthermore, our results indicate the occurrence of additional genetic aberrations providing a rational base for novel targeted therapeutic approaches. Citation Format: Marcel Trautmann, Magdalene Cyra, Ilka Isfort, Inga Grünewald, Konrad Steinestel, Sebastian Huss, Reinhard Büttner, Eva Wardelmann, Wolfgang Hartmann. Extraskeletal myxoid chondrosarcoma: a clinicopathologic and molecular study reveals novel genetic aberrations by targeted next-generation sequencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2703. doi:10.1158/1538-7445.AM2017-2703

Extraskeletal myxoid chondrosarcoma (EMCS) is a rare malignant soft tissue tumor that usually develops in the deep parts of the proximal extremities and limb girdles in middle-aged adults. Its biologic behavior and pathogenesis are poorly understood. EMCS has a prolonged and indolent clinical course, with a high rate of local recurrences and distant metastases before tumor-related death. The diagnosis and management of this tumor must be early and multidisciplinary.

We report a rare case of extraskeletal myxoid chondrosarcoma (EMC) involving the jugular foramen and cerebellopontine angle. A 39-year-old male patient presented with initial complaints of headaches, unilateral hearing loss, and loss of balance. Cranial magnetic resonance imaging revealed an enhancing multilobulated right jugular foramen mass with medial upward extension into the cerebellopontine angle and lateral downward extension into the carotid-jugular space. The patient was preoperatively diagnosed with having a paraganglioma solely due to the tumor localization and magnetic resonance imaging finding of strong enhancement patterns. However, upon surgical resection of the intracranial component of the tumor via right lateral suboccipital craniectomy, cytologic and subsequent histopathologic examination helped delineate the diagnosis of EMC. Given the rarity of tumors involving both jugular foramen and cerebellopontine angle, we discuss histopathologic differentiating features and diagnostic pitfalls between EMC and other possible mimickers.

Extraskeletal myxoid chondrosarcoma (EMC) is a rare tumour and usually occurs in the soft tissue of the extremities. Problems can occur when the site is unusual and the cellular differentiation is not distinct. Chest wall is an unusual site for EMC. When aspiration cytology of breast mass yields polygonal cells with no significant pleomorphism in a prominent myxoid/mucoid background, one should take into consideration the possibility of EMC of the anterior chest wall before diagnosing it as breast carcinoma, as both the entities have different treatment modalities. We present a case in which EMC of the anterior chest wall presented as a breast mass in a 55-year-old female patient; it was misdiagnosed as mucinous/myxoid carcinoma of the breast on fine-needle aspiration cytology, and subsequently, correct diagnosis was made on histopathological examination. This case has been highlighted for the unusual site of occurrence of EMC and its close similarity to breast carcinoma, both clinically and cytologically.

Chordoid meningioma, World Health Organization grade II, is an uncommon variant of meningioma with a propensity for aggressive behavior and increased likelihood of recurrence. As such, recognition of this entity is important in cases that show similar morphologic overlap with other chondroid/myxoid neoplasms that can arise within or near the central nervous system. A formal comparison of the immunohistochemical features of chordoid meningioma versus tumors with significant histologic overlap has not been previously reported. In this study, immunohistochemical staining was performed with antibodies against D2-40, S100, pankeratin, epithelial membrane antigen (EMA), brachyury, and glial fibrillary acidic protein (GFAP) in 4 cases of chordoid glioma, 6 skeletal myxoid chondrosarcomas, 10 chordoid meningiomas, 16 extraskeletal myxoid chondrosarcoma, 18 chordomas, 22 low-grade chondrosarcomas, and 27 enchondromas. Staining extent and intensity were evaluated semiquantitatively and mean values for each parameter were calculated. Immunostaining with D2-40 showed positivity in 100% of skeletal myxoid chondrosarcomas, 96% of enchondromas, 95% of low-grade chondrosarcomas, 80% of chordoid meningiomas, and 75% of chordoid gliomas. Staining with S100 demonstrated diffuse, strong positivity in all (100%) chordoid gliomas, skeletal myxoid chondrosarcomas, low-grade chondrosarcomas, and enchondromas, 94% of chordomas, and 81% of extraskeletal myxoid chondrosarcomas, with focal, moderate staining in 40% of chordoid meningiomas. Pankeratin highlighted 100% of chordoid gliomas and chordomas, 38% of extraskeletal myxoid chondrosarcomas, and 20% of chordoid meningiomas. EMA staining was positive in 100% of chordoid gliomas, 94% of chordomas, 90% of chordoid meningiomas, and 25% of extraskeletal myxoid chondrosarcomas. Brachyury was positive only in the chordomas (100%), whereas GFAP was positive only in the chordoid gliomas (100%). EMA was the most effective antibody for differentiating chordoid meningioma from skeletal myxoid chondrosarcoma, low-grade chondrosarcoma, and enchondroma, whereas D2-40 was the most effective antibody for differentiating chordoid meningioma from extraskeletal myxoid chondrosarcoma and chordoma. Our findings demonstrate that in conjunction with clinical and radiographic findings, immunohistochemical evaluation with a panel of D2-40, EMA, brachyury, and GFAP is most useful in distinguishing chordoid meningioma from chordoid glioma, skeletal myxoid chondrosarcoma, extraskeletal myxoid chondrosarcoma, chordoma, low-grade chondrosarcoma, and enchondroma. A lack of strong, diffuse S100 reactivity may also be useful in excluding chordoid meningioma. Among the neoplasms evaluated, brachyury and GFAP proved to be both sensitive and specific markers for chordoma and chordoid glioma, respectively. Of note, this study is the first to characterize the D2-40 immunoprofile in extraskeletal myxoid chondrosarcoma, results that could be of utility in differential diagnostic assessment.

Extraskeletal myxoid chondrosarcoma presenting in the head and neck is extremely rare. Histologic diagnosis is difficult and close co-operation among clinician, radiologist and pathologist is recommended. The tumour has a better prognosis than myxoid chondrosarcoma of the bone but surgical resection may be difficult due to its gelatinous nature. We present a case of extraskeletal myxoid chondrosarcoma originating in the left nasal cavity of a 35-year-old woman.

STRAIGHT TO THE LUNGS: UNUSUAL ETIOLOGY OF BILATERAL PULMONARY OPACITIES

A case of extraskeletal myxoid chondrosarcoma (EMC) in which there was histochemical, immunohistochemical, and ultrastructural evidence of neuroendocrine differentiation is reported. Genetic investigations showed the recently described novel translocation t(9;17)(q22;q11.2) and associated fusion of the CHN and RBP56 genes, contrasting with the translocation t(9;22)(q22;q12) and EWS/CHN gene fusion found in the majority of EMCs.

Introduction: Extra skeletal myxoid chondrosarcoma is a rare soft tissue tumor. It is a low-grade sarcoma, arising mainly in the deep tissues and musculature of the extremities, with a histological resemblance to its bony counterpart. It accounts for less than 3% of soft tissue sarcomas, and localizes mainly in the upper extremity, shoulder, neck, orbit but also intra-abdominally. It is a tumor with a high metastatic potential and an unfavorable long-term prognosis. Extra skeletal myxoid chondrosarcoma is a tumor occurring in middle-aged patients regardless of gender or race. Treatment is multimodal including surgery, radiation therapy and chemotherapy. Case presentation: A 37-year-old female patient consulted for a subcutaneous swelling on the sole of the left foot opposite the 5th toe; evolving for approximately six years. The clinical examination and the paraclinical work-up revealed a mass that encompassed the diaphysis of the 5th metatarsal with cortical lysis opposite. This mass arrived medially at the contact of the 4th metatarsal without cortical lysis. The extension work-up was unremarkable. The histological, immunohistochemical and molecular biology examination of the surgical biopsy concluded to an extra skeletal myxoid chondrosarcoma. Polychemotherapy with andriamycin and Ifosfamide, surgery and radiotherapy at a dose of 50Gy was performed. Conclusion: Rare tumor and of difficult diagnosis, the key of the diagnosis lies in molecular biology. Survival is often prolonged despite its local aggressiveness.

Coexpression of NOR1 and SIX3 proteins in extraskeletal myxoid chondrosarcomas without detectable NR4A3 fusion genes

Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft tissue sarcoma usually presenting in proximal extremities of middle-aged men. The authors discuss a unique case of EMC, localized in the plantar foot of a 76-year-old woman, clinically suspected as plantar fibromatosis. It is important to avoid misdiagnosis of EMC because of their propensity for late recurrence and their metastatic potential.

Background: Chordomas are rare malignant tumors derived from notochordal remnants, accounting for 1–4% of skeletal malignancies. These slow-growing tumors most commonly affect the sacrum, skull base, and spine, posing significant challenges due to their anatomical location near critical neural structures. Despite their low metastatic potential, chordomas have a high local recurrence rate, necessitating aggressive surgical intervention. Methods: A narrative review of the literature was conducted, analyzing studies on the surgical management and adjuvant radiotherapy of spinal chordomas. Electronic databases, including MEDLINE, Scopus, ProQuest, and Google Scholar, were searched using relevant keywords. The retrieved studies were reviewed to assess surgical approaches, complications, outcomes, and the role of radiation therapy in treatment. Results: En-bloc resection with negative margins remains the primary treatment approach for spinal chordomas, though achieving complete excision is challenging due to anatomical constraints. Advances in radiotherapy, including proton beam and carbon ion therapy, have shown promise as adjunct treatments, especially when gross total resection is not possible. However, the benefit of adjuvant radiation remains debated. Postoperative complications, such as infections, neurological deficits, and mechanical instability, highlight the need for a multidisciplinary approach in patient management. Conclusion: The management of spinal chordomas requires an individualized treatment approach, balancing surgical feasibility, functional preservation, and disease control. While en-bloc resection remains the gold standard, newer radiotherapy techniques may improve outcomes in select cases. A multidisciplinary team is essential to optimize prognosis and quality of life for affected patients.

Haemangiopericytomas of central nervous system (CNS) were first defined as a separate entity in 1942. Previously they were either considered to be a histological variant of an angioblastic meningioma or a distinctive mesenchymal neoplasm. Most commonly they are located in parasagittal and falcine region. Tumours in the sellar/parasellar location are very rare and commonly escape diagnosis before operation. They are characterised by high vascularity, a high rate of local recurrence and extraneuronal metastasis. We report a 35-year-old man with a suprasellar hemangiopericytoma who presented with bilateral diminution of vision in both eyes and frontal headache. Six months after the first operation, he developed a large local recurrence. He again underwent tumour decompression followed by postoperative conformal radiotherapy and is currently asymptomatic and stable clinically and radiologically. The various differential diagnoses, the importance of a preoperative suspicion of this diagnosis and management are issues discussed in this illustrated review.

15645 Background: Penile cancer is a rare malignancy in the Western world with limited published data. We conducted a review of patient (pt.) records diagnosed with penile cancer at our instituition to evaluate the patterns of treatment, responses, recurrences and long term outcomes. Methods: IRB approval was obtained for this retrospective analysis. Tumor registry data was analysed for all adult patients diagnosed with penile cancers between 1995 and 2005. Patient characteristics including age, disease stage, histology, grade, ethnicity, treatment modalities and outcomes were recorded. Results: 24 pts were identified. Median age: 68 years (range: 38 - 86), Stage distribution: Stage 0 (n=7, 29%), Stage I: n =8 (33.%) ; Stage II: n= 4 (17%); Stage III: n = 1 (4%), Stage IV: n=4 (16.7%); ethnicity: Caucasian:17, African-American: n=3; Hispanic: n=1;and South Asian: n=6; Histology: squamous (sq.): n = 21(88%), sq. with sarcomatoid features: n=1(4%), small cell ca: n = 1, (4%); poorly diff. ca: n = 1 (4%). Grades 1,2,3 in each stage respectively : stage I: ( n= 4, 2, 1), stage II: (n = 0,1,2), stage III: (1,0,0), stage IV: (n = 1,2,1). Treatment and Outcome: All pts with stage 0 disease were treated with excision biopsy. 3 of 7 (40%) recurred but are disease free after re-excision. All pts with Stage I disease were treated with partial penectomy. Two of 8 (25%) recurred, of which one pt died of his disease. All pts with stage II were treated with surgery (penectomy) and CT. One pt was additionally treated with RT to the groin. Except for this pt all stage II pts recurred and died due to recurrent disease. The pt with stage III disease was treated with a partial penectomy and CT and remains disease free without recurrence. All pts with stage IV disease were treated with CT, 3 were also treated with RT , but all died of metastatic disease. Median OS: Stage 0: 70+ mo, (20–150 ); Stage I: 69 mo (11–133); Stage II: 25 mo(12–84); Stage III: 25 mo; Stage IV: 7 mo ( 7- 23); Conclusions: Pts with early stage 0 and I disease have a high local recurrence rate (33%) but are curable with surgical salvage. Stages II, III and IV pts have high recurrence rates and poor prognoses despite treatment with penectomy and CT. Future trials should address the benefit of adjuvant chemo/RT in patients with intermediate stage (II & III) disease. No significant financial relationships to disclose.

Desmoid tumors are monoclonal proliferations that fall within a broad histologic spectrum of fibrous mesenchymal tumors that ranges from benign proliferations of scar tissue to high-grade fibrosarcomas. These low-grade tumors are extremely infiltrative locally, but lack the ability to metastasize systemically. While they are only rarely a direct cause of mortality, using current therapeutic modalities, these tumors have a high rate of local recurrence that can result in significant treatment related morbidity. Sporadic desmoids are usually associated with somatic mutations in codons 41 or 45 of exon 3 of beta-catenin (CTNNB1). Desmoid tumors occurring in the background of familial adenomatous polyposis (FAP) usually contain inactivating germline mutations in the adenomatous polyposis coli (APC) gene. CTNNB1 and APC are part of the Wnt signaling pathway and mutations in either gene result in stabilization of the beta-catenin protein and allow nuclear translocation and binding of beta-catenin to the T-cell factor/lymphoid enhancer factor (TCF/Lef) family of transcription factors, resulting in activation of target genes which may underlie desmoid tumor biology and clinical behavior. In an era of molecularly targeted therapeutics there is a real need to better grasp the molecular mechanisms behind desmoid tumorigenesis and progression. This knowledge will eventually result in the development of patient and tumor tailored therapies and assist in the control and eradication of this disease.