malignant granular cell tumor

Definition: Malignant granular cell tumor is a high-grade sarcoma with a high rate of metastases and a short survival.

Six histologic criteria can be be 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
 pleomorphism

Neoplasms that met three or more of these criteria can be classified as histologically malignant.

Those that meet one or two criteria were classified as atypical.
Those that display only focal pleomorphism but fulfilled none of the other criteria were classified as benign.

Immunohistochemistry

 100% expressed vimentin
 98% S-100 protein
 98% neuron-specific enolas
 69% CD57
 65% CD68

Alpha-smooth muscle actin, desmin, epithelial membrane antigen (EMA), cytokeratins (with CAM 5.2 and KL-1), chromogranin, and HMB45 are not detected.

The proliferative index with Ki67 (MIB 1) is 10-50% in 56% of malignant tumors.

Immunostaining for p53 was detected in 50% or more of tumor cells.

Ultrastructure

Ultrastructural examination of benign, atypical, and malignant granular cell tumors showed engorgement of the cytoplasm with complex granules and lysosomes, as well as Schwannian features.

In a study by flow cytometric DNA analysis, two of six malignant tumors were aneuploid, two were hyperdiploid, and two were diploid.

Prognosis

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%.

References

 Malignant granular cell tumor of soft tissue: diagnostic criteria and clinicopathologic correlation. Fanburg-Smith JC, Meis-Kindblom JM, Fante R, Kindblom LG. Am J Surg Pathol. 1998 Jul;22(7):779-94. PMID: 9669341