Malignant Granular Cell Tumor of Soft Tissue

Abstract

Seventy-three cases of malignant, atypical, and multicentric granular cell tumors of soft tissue were studied to clarify criteria for malignancy and prognostic factors. Six histologic criteria were assessed: necrosis, spindling, vesicular nuclei with large nucleoli, increased mitotic activity (> 2 mitoses/10 high-power fields at 200x magnification), high nuclear to cytoplasmic (N:C) ratio, and pleomorphism. Neoplasms that met three or more of these criteria were classified as histologically malignant; those that met one or two criteria were classified as atypical; and those that displayed only focal pleomorphism but fulfilled none of the other criteria were classified as benign. Hence, 46 cases were classified as histologically malignant, 21 as atypical (3 were multicentric), and 6 as benign (all were multicentric). The patients with benign multicentric and atypical granular cell tumors had no metastases and there were no tumor deaths. In contrast, 11 of 28 patients (39%) with malignant granular cell tumor with follow-up information died of disease at a median interval of 3 years; 8 of 28 (29%) were alive with disease, and 9/28 (32%) were disease free (median intervals, 2 and 7 years, respectively). There were local recurrences in 9 of 28 malignant cases (32%) and metastases in 14 of 28 (50%) (median intervals, each 2 years). Forty-eight cases were studied immunohistochemically; 100% expressed vimentin, 98% S-100 protein, 98% neuron-specific enolase, 69% CD57, and 65% CD68. Alpha-smooth muscle actin, desmin, epithelial membrane antigen (EMA), cytokeratins (with CAM 5.2 and KL-1), chromogranin, and HMB45 were not detected. The proliferative index with Ki67 (MIB 1) was 10-50% in 14 of 25 malignant tumors (56%), and immunostaining for p53 was detected in 50% or more of tumor cells in 17 of 25 (68%); both of these factors were statistically significant with regard to the histologic classification as benign, atypical, or malignant. Ultrastructural examination of 13 benign, atypical, and malignant granular cell tumors showed engorgement of the cytoplasm with complex granules and lysosomes, as well as Schwannian features. By flow cytometric DNA analysis, two of six malignant tumors were aneuploid, two were hyperdiploid, and two were diploid. One atypical tumor was aneuploid and all 11 benign tumors were either diploid (9 cases) or hyperdiploid (2 cases). Statistically significant adverse prognostic factors with regard to survival included local recurrence, metastasis, larger tumor size, older patient age, histologic classification as malignant, presence of necrosis, increased mitotic activity, spindling of tumor cells, vesicular nuclei with large nucleoli, and Ki67 values greater [corrected] than 10%. This study defines clinical and morphologic criteria for malignancy in granular cell tumors and shows that malignant granular cell tumor is a high-grade sarcoma with a high rate of metastases and a short survival.

Typical Aspects of the Granular Cell Tumor of the Oral Cavity

“…GCT that met three or more of these criteria has been classified as histologically malignant, while the presence of one or two criteria defines an atypical GCT. The isolated presence of focal polymorphism can be observed in benign tumors [9]. On the other hand, the benign histopathological picture has been also reported in clinically malignant lesions, which highlights the importance of careful clinical examination.…”

“…A classic study reported 39% of survival rate for malignant GCT at a median interval of 3 years and 29% of patients were alive with disease [9]. Six histologic features are used distinguishing benign, atypical, and malignant granular cell tumors: 1) necrosis; 2) spindling; 3) vesicular nuclei with large nucleoli; 4) increased mitotic activity (>2 mitoses/10 high-power fields at 200× magnification); 5) high nuclear to cytoplasmic (N:C) ratio; and 6) nuclearpleomorphism.…”

Benign Granular Cell Tumor of the Vulva: First Report of Multiple Cases in a Family

“…Adverse clinical prognostic factors for malignancy are local recurrence, the presence of metastases, old age and size >4 cm [20]. This review highlights that malignant lesions are greater in size (6.34 vs. 2.6 cm), but does not support that patients with malignant lesions are older (45.81 years for benign tumors vs. 40.33 years for the malignant form).…”

“…The potentially malignant behavior of these tumors is often ignored, and is discovered only after local recurrence or distant metastases occur, especially when the primary GCT showed no histologic features of malignancy. In an attempt to define clinical features associated with increased malignant potential, Fanburg-Smith et al [20] classified GCTs as malignant if three or more of the following criteria were met: increased mitotic activity, presence of tumor necrosis, large nucleoli, prominent spindling, high nuclear:cytoplasmic ratio and pleomorphism. They also evaluated the immunohistologic criteria and reported that the expression of p53 and Ki-67 was significantly higher in malignant tumors.…”

Granular Cell Tumor of the Intrapancreatic Common Bile Duct: One Case Report and Review of the Literature

“…The pathogenesis of this lesion is still poorly understood and a matter for discussion; strong evidence of Schwann cell origin has been recently suggested by ultrastructural and immunohistiochemical reports [4^8]. GCT is generally considered a benign tumor, but the malignant counterpart exists, although it is extremely rare [9,10]. This report concerns one case of GCT localized in the intrapancreatic tract of the common bile duct and with a peculiar clinical presentation.…”