We show the benefits of denosumab as adjuvant treatment of gnathic central giant cell granulomas (CGCGs) in 3 female patients, ages 18 to 65. This case series contributes to the growing experience in the medical therapy of these aggressive lesions, and demonstrates denosumab’s potential to decrease surgical morbidity. Central giant cell lesions of the jaw can be locally aggressive and thereby result in severe tissue destruction. Several medications have been evaluated as adjuvant therapy for CGCGs, with investigation of denosumab being the most recent. Our goal was to definitively treat patients with large CGCGs while minimizing unnecessary tissue and function loss. All 3 patients were offered adjuvant therapy with denosumab, since surgical resection alone would have resulted in large segmental defects requiring jaw reconstruction with free tissue transfer. Treatment instead consisted of lesion curettage and adjuvant denosumab therapy. The denosumab treatment protocol we used was based on what is currently recommended for unresectable giant cell tumors of bone (GCTB). Patients have been monitored for 40 months with clinical and radiographic exams, and 2 of them have also had histological evaluation following initiation of denosumab treatment. The 3 patients improved subjectively after the first few denosumab injections and had objective clinical and radiographic improvement after less than 6 months of therapy. Medication treatment length ranged from 10 to 15 months. Radiographic exams showed cortical thickening, resolution of cortical perforations, and calcification within a previously radiolucent region. Our findings are consistent with previous reports, and further support for the use of denosumab in locally aggressive central giant cell lesions. Our patients have thus far avoided large segmental resections, temporomandibular joint disarticulation, and sensory loss which would have resulted from surgical treatment alone. These 3 cases show that denosumab can be effective as adjuvant therapy in the treatment of aggressive gnathic CGCGs.

OBJECTIVES:Desmoplastic small round cell tumor (DSRCT) is an aggressive round cell sarcoma that arises in the abdominal cavity/pelvis of young males. We sought to expand its clinicopathologic spectrum.METHODS:Cases of DSRCT presenting in patients >30 years of age or tumors arising outside of the abdominal cavity/pelvis were retrieved.RESULTS:Thirty-four cases were identified. Sixteen tumors arose at atypical sites (head/neck, intracranial, thigh, axilla/shoulder, inguinal/paratesticular, intraosseous, and uterine corpus). The remaining 18 patients were older than 30 years, and their tumors involved the abdomen or pelvis. The majority of cases showed areas with classic histology, while 6 cases exhibited solid growth and 5 showed macronodular architecture. Cytologic appearance included round cell, rhabdoid, epithelioid, and small cell.CONCLUSION:DSRCT may arise at nonabdominal locations in both pediatric and adult populations, as well as intra-abdominally in older adults, and these tumors exhibit high rates of metastasis and morbidity.

While the clinicopathologic features of pediatric vestibular schwannomas, often in the context of neurofibromatosis type 2 (NF2), have been well studied, there is less data regarding the characteristics of pediatric non-vestibular schwannomas (NVS). Additionally, the rate of loss of SMARCB1/INI1 expression in this population has not been systematically evaluated. Our institutional archives were searched for cases of NVS arising in patients 18 years or younger. Clinicopathologic features including SMARCB1/INI1 status were assessed for each case. Twenty-three NVS from 9 males and 13 females (age range, 2 months to 18 years) were identified, and sites included paraspinal (n = 10), head and neck (n = 6), extremities (n = 4), trunk (n = 1), mediastinum (n = 1), and retroperitoneum (n = 1); 22 cases were Antoni A predominant with 6 cases comprising solely Antoni A tissue. The mitotic rate of the tumors ranged from 0 to 10/10 high-power fields (HPFs), and 3 tumors had mitotic rates of ≥4 mitoses/10 HPFs. Two tumors showed plexiform architecture. No NVS showed diffuse atypia, calcifications, microcystic/reticular architecture, epithelioid morphology, pseudoglandular change, neuroblastoma-like features, or necrosis. All tumors tested (23/23) showed retained nuclear expression of SMARCB1/INI1. Follow-up was available in 21 patients (range 1 week to 194 months), and 5 tumors recurred. Pediatric NVS have a relatively homogeneous appearance with a predominance of Antoni A areas. Pathologists should be aware that schwannomas in this age group may be cellular with mitotic rates of ≥4/10 HPFs to avoid misclassification as a spindle cell sarcoma.

OBJECTIVES:Most giant cell tumors of bone (GCTs) occur in patients aged 20 to 40 years. We analyzed features of GCT in patients 55 years or older.METHODS:GCTs were examined for fibrosis, matrix, cystic change, histiocytes, mitoses, and necrosis. Clinical/radiologic data were collected.RESULTS:Thirty-four (5%) of 710 GCTs occurred in patients older than 55 years (14/20 male/female; 56-83 years) in long bones (n = 24), vertebrae (n = 6), pelvis (n = 3), and metacarpal (n = 1). Imaging was classic in 26 of 27 cases; one case appeared malignant. Morphologic patterns included fibrosis (n = 29), bone formation (n = 19), cystic change (n = 8), necrosis (n = 8), foamy histiocytes (n = 7), and secondary aneurysmal bone cyst formation (n = 1). Mitoses ranged from 0 to 18 per 10 high-power fields. Six recurred; one patient developed metastasis. Four of five cases harbored H3F3A mutations.CONCLUSIONS:GCTs in patients 55 years or older share pathologic characteristics with those arising in younger adults. Fibrosis and reactive bone are common, potentially leading to diagnostic confusion in this population. No histologic features correlate with adverse outcome.