Primary gallbladder sarcoma: a clinicopathologic study of 15 cases, heterogeneous sarcomas with poor outcome, except pediatric botryoid rhabdomyosarcoma.

BACKGROUND: Primary gallbladder sarcoma (PGBS) is rare, with only 39 documented cases, with the predominant type being leiomyosarcoma.
DESIGN: Cases recorded as "gallbladder sarcoma" were retrieved from our files; the clinicopathologic features were reviewed and recorded. Only primary gallbladder wall mesenchymal tumors were included. Epithelial tumors, mixed tumors (carcinosarcoma or sarcomatoid carcinoma), tumors extending into the gallbladder from the abdomen, or sarcoma with other known primaries were excluded. RESULT: PGBS occurred in 4 males and 11 females with the adult median age of 68.5 (range: 24 to 88 y, n=12) and 3 children ages 1.5 to 3 years, the latter all with botryoid embryonal rhabdomyosarcoma. Patients presented with acute and/or chronic cholecystitis, abdominal pain, weight loss, pruritus, elevated alkaline phosphatase and bilirubin, and leukocytosis. The median tumor size was 4.5 cm, mean tumor size 5.7 cm, and range 2.0 to 14.0 cm. Most PGBS involved the entire wall and ulcerated the mucosa. PGBSs were diagnosed as 7 myxofibrosarcomas [malignant fibrous histiocytoma, storiform pleomorphic to myxoid, 2 with an unusual fibromyxoid sarcoma-like (Evans-like), and pleomorphic hyalinizing angiectatic tumor-like mixture], 2 leiomyosarcomas, 1 gastrointestinal stromal tumor-like (GIST-like), 3 botryoid embryonal rhabdomyosarcomas (RMS), and 2 epithelioid angiosarcomas. Diagnosis was based on morphology and immunohistochemistry. A diagnosis of LMS required myoid-intersecting fascicles and diffuse, strong immunoreactivity for smooth muscle actin +/- desmin. RMS revealed myxoid grape-like hypocellular tumor with stellate cells, mild atypia, mitoses and desmin, and myoregulatory protein (MyoD1) and skeletal muscle-specific myogenin (Myf4) reactivity. The GIST-like sarcoma was palisaded and myoid-like but failed to stain for CD34 or CD117. Angiosarcomas demonstrated an extravascular proliferation of atypical epithelioid endothelial cells, and mitotic activity. All cases were negative for S100 protein, HMB45, keratins, and CK18. All patients received cholecystectomy and 6 known adjuvant therapy. Follow-up of 12 revealed that 7 patients died of disease within 3 weeks to 1 year and 4 months after diagnosis, 3 died of unknown causes, and 2, both adjuvant therapy treated botryoid RMS in young children, were alive without disease 11 and 27 years later.
CONCLUSIONS: PGBSs are rare. Carcinosarcoma, spindle cell carcinoma (by use of keratins and CK18), and melanoma must first be excluded. A variety of sarcoma types are found, yet malignant fibrous histiocytoma is the predominant variant, more common than LMS. GIST is a controversial sarcoma in gallbladder; angiosarcoma can rarely occur in this location. PGBS mainly occur in older female adults and have overall poor prognosis. A subgroup of adjuvant therapy-treated botryoid embryonal RMS in the gallbladder of young children, although rare, can have excellent prognosis.