Head & Neck Case Review
A 44-year-old woman presented with a 2-month history of right mandibular pain and mild swelling. Recent developments included paresthesia along the lip and right side of the chin. A cone beam CT study showed irregular resorption of bone including erosion of the buccal cortex. Representative axial and coronal slices of the mass along with the H&E stained sections and immunostains of the biopsied tissue are shown.
Q1. What is the characteristic genetic event in this tumor in children?
- A. PAX 3/7-FOX01 gene fusion
- B. FGFR4, RAS, AKT pathway mutations
- C. PTEN hypermethylation
- D. NCOR2 or VGLL2 gene fusion
Q2. Which one of the following is a morphologic variant of this tumor?
- A. Sclerosing
- B. Embryonal
- C. Pleomorphic
- D. Alveolar
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.
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- Nascimento AF, Fletcher CD. Spindle cell rhabdomyosarcoma in adults. Am J Surg Pathol. 2005;29:1106–13.
- 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.
- 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.
- 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.
- 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.
Q1 = D. NCOR2 or VGLL2 gene fusion
Q2 = A. Sclerosing
Yeshwant B. Rawal, BDS, MDS, MS
Professor, Department of Surgical Sciences
Marquette University School of Dentistry, Milwaukee, WI