Tag: mandible

Low-grade central osteosarcoma (LGCOS)

This is a low-grade central osteosarcoma (LGCOS), a rare intramedullary osteosarcoma that typically affects the metaphysis of long bones, predominantly the femur. It is commonly seen in young adults, and typically presents as a sclerotic expansile lesion on imaging.

Histologically, this lesion is composed of thick woven and lamellar bony trabeculae rimmed by osteoblasts and exhibiting pagetoid change, growing within a mildly hypercellular fibrosclerotic stroma. There are no mitotic figures or tumor necrosis. The tumor appears to infiltrate into the roots of the molar tooth with expansile growth into soft tissue. Fluorescence in-situ hybridization was performed and confirmed the presence of MDM2 amplification (12q13-q15), which is associated with this tumor. Of note, MDM2 amplification is similarly seen in other soft tissue tumors, including well-differentiated liposarcoma, dedifferentiated liposarcoma, and intimal sarcoma.

The main histologic differential diagnosis for this lesion is a benign fibro-osseous lesion such as fibrous dysplasia (FD). The latter does not invade cortical bone, teeth, or soft tissue, and does not exhibit MDM2 amplification. FD, however, has an activating missense mutation in GNAS gene. Parosteal osteosarcoma may have an identical histologic appearance as well as MDM2 amplification but arises from the cortical surface of bone.

Reference

1. Nielson GP, Yoshida A, Bredella MA. et al. Low-grade central osteosarcoma. In: WHO Classification of Tumours Editorial Board. Soft tissue and bone tumours [Internet]. Lyon (France): International Agency for Research on Cancer; 2020 [cited 2024 Feb 1]. (WHO classification of tumours series, 5th ed.; vol. 3). Available from: https://tumourclassification.iarc.who.int/chapters/33/152

Quiz Answers

Q1 = B. MDM2 amplification

Q2 = False

Spindle cell rhabdomyosarcoma of the mandible

Spindle cell/sclerosing rhabdomyosarcomas are a rare subtype of rhabdomyosarcomas accounting for 3–10% of rhabdomyosarcomas, affecting adults and children. In adults, the deep soft tissue of the head and neck region is most commonly involved, accounting for over 50% of the cases. In children, the paratesticular region is the most common site followed by the head and neck. Tumors in adults and children are more common in males with a male to female ratio of 6:1.  

Spindle cell rhabdomyosarcomas show an infiltrative cellular proliferation of spindle-shaped tumor cells having elongated hyperchromatic nuclei and pale eosinophilic cytoplasm arranged in intersecting fascicular or herringbone patterns. A storiform pattern may also be seen, focally. Scattered rhabdomyoblasts with eccentrically placed nuclei may also be seen. Sclerosing rhabdomyosarcomas are characterized by prominent hyalinization or sclerosis with tumor cells arranged in cord, nests, trabecular, or microalveolar patterns. Tumors expressing a sclerosing morphology are more common in the limbs. Immunohistochemically, the tumor cells are positive for desmin, myogenin, and MyoD1. Some tumors show only very limited immunoreactivity for desmin and myogenin but are often strongly positive for MyoD1.

Infantile/childhood spindle cell/sclerosing rhabdomyosarcomas show a NCOR2– or VGLL2-related gene fusion.  MYOD1 (L122R)-mutant subset is more common among adults and is associated with an aggressive clinical outcome.  The MYOD1-mutant subset occasionally shows a PIK3CA mutation. A third subset of tumors lack recurrent genetic abnormalities. Rare intraosseous spindle cell rhabdomyosarcomas harbor a gene fusion of EWSR1/FUSTFCP2 and MEIS1-NCOA2.

Adult tumors are clinically aggressive. Recurrence and metastasis are reported in 50% of cases with metastasis to lymph nodes and lungs being common. Radiotherapy & function-preserving surgery are mainstay of treatment for resectable sarcomas. Intensive multi-agent therapy is used in patients with high-risk rhabdomyosarcomas. These include dose-compressed cycles of Ifosfamide/Etoposide and Vincristine/Doxorubicin/Cyclophosphamide and radiation. However, the prognosis is poor.

In contrast to the adult tumors, childhood tumors demonstrate a low stage at presentation. The prognosis is good in patients under 10 years of age with over 95% survival at 5 years.

References

1. Chiles MC, Parham DM, Qualman SJ, Teot LA, Bridge JA, Ullrich F, Barr FG, Meyer WH; Soft Tissue Sarcoma Committee of the Children’s Oncology Group. Sclerosing rhabdomyosarcomas in children and adolescents: a clinicopathologic review of 13 cases from the Intergroup Rhabdomyosarcoma Study Group and Children’s Oncology Group. Pediatr Dev Pathol. 2004;7:583–94.
2. Nascimento AF, Fletcher CD. Spindle cell rhabdomyosarcoma in adults. Am J Surg Pathol. 2005;29:1106–13.
3. Alaggio R, Zhang L, Sung YS, Huang SC, Chen CL, Bisogno G, Zin A, Agaram NP, LaQuaglia MP, Wexler LH, Antonescu CR. A Molecular Study of Pediatric Spindle and Sclerosing rhabdomyosarcoma: Identification of Novel and Recurrent VGLL2-related Fusions in Infantile Cases. Am J Surg Pathol. 2016;40(2):224–35.
4. Rekhi B, Upadhyay P, Ramteke MP, Dutt A. MYOD1 (L122R) mutations are associated with spindle cell and sclerosing rhabdomyosarcomas with aggressive clinical outcomes. Mod Pathol. 2016;29(12):1532–40.
5. Nascimento AF, Barr FG. Spindle cell/Sclerosing rhabdomyosarcoma. Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F, eds. In: WHO classification of tumours of soft tissue and bone. Lyon, IARC Press, 2013:134–5.
6. Agaram NP, LaQuaglia MP, Alaggio R, Zhang L, Fujisawa Y, Ladanyi M, Wexler LH, Antonescu CR. MYOD1-mutant spindle cell and sclerosing rhabdomyosarcoma: an aggressive subtype irrespective of age. A reappraisal for molecular classification and risk stratification. Mod Pathol. 2019;32:27–36.

Quiz Answers

Q1 = D. NCOR2 or VGLL2 gene fusion

Q2 = A. Sclerosing