Atypical and malignant glomus tumors - Analysis of 52 cases, with a proposal for the reclassification of glomus tumors

Occasional glomus tumors display unusual features, such as large size, deep location, infiltrative growth, mitotic activity, nuclear pleomorphism, and necrosis. Although a small number of purportedly malignant glomus tumors h ave been described, histologic criteria for malignancy in glomus tumors hav e never been elaborated. The authors studied 52 unusual glomus tumors (retr ieved from their consultation files) previously diagnosed as "atypical" or "malignant" by virtue of nuclear atypia, infiltrative growth, or mitotic ac tivity. They evaluated size, depth, growth pattern, cellularity, nuclear gr ade, number of mitotic figures per 50 high-power fields (HPF), atypical mit otic figures, vascular space involvement, and necrosis to define criteria f or malignancy in glomus tumors. Estimated relative risk was calculated and the Fisher exact test was used for statistical analysis. The 27 female pati ents and the 25 male patients ranged in age from 8 to 83 years (median age, 43 years). The rumors measured from 0.2 to 12 cm (median size, 2 cm) and o ccurred predominantly in the extremities, in both the superficial (n = 35) and deep (n = 17) soft tissues. Atypical features were usually observed cen trally with a rim of benign-appearing glomus tumor. Follow-up information ( n = 35; range, 5 months-23 years; mean 5.5 years) showed seven recurrences, eight metastases, and seven deaths from disease. Five-year cumulative meta static risk increased significantly for tumors with a deep location (p = 0. 005), with a size of more than 2 cm (p = 0.004), and with atypical mitotic figures (p = 0.004). Mitotic activity of more than 5 mitoses/50 HPF, high c ellularity, the presence of necrosis, and moderate to high nuclear grade ap proached but did not reach significance. High nuclear grade alone, infiltra tive growth, and vascular space involvement were not associated with metast asis. The authors propose the following classification scheme and criteria. Malignant glomus tumor: Tumors with a deep location and a size of more tha n 2 cm. or atypical mitotic figures, or moderate to high nuclear grade and greater than or equal to5 mitotic figures/50 HPF. Symplastic glomus tumor: Tumors with high nuclear grade in the absence of any other malignant featur e. Glomus tumor of uncertain malignant potential: Tumors that lack criteria for malignant glomus tumor or symplastic glomus tumor but have high mitoti c activity and superficial location only, or large size only, or deep locat ion only. Glomangiomatosis: Tumors with histologic features of diffuse angi omatosis and excess glomus cells. Using this classification scheme, metasta sis was observed in 38% of tumors fulfilling the criteria for malignancy. I n contrast, metastatic disease was not seen in any specimen classified as s ymplastic glomus tumor, glomus tumor of uncertain malignant potential, or g lomangiomatosis.