Is fine needle aspiration cytology a useful diagnostic tool for granular cell tumors? A cytohistological review with emphasis on pitfalls

Abstract

Background:Granular cell tumors (GCT) formerly known as Abrikossoff tumor or granular cell myoblastoma, are rare neoplasms encountered in the fine needle aspiration (FNA) service. Named because of their highly granular cytoplasm which is invariably positive for the S-100 antibody, the classic GCT is thought to be of neural origin. The cytomorphological features range from highly cellular to scanty cellular smears with dispersed polygonal tumor cells. The cells have abundant eosinophilic granular cytoplasm, eccentric round to oval vesicular nuclei with small inconspicuous nucleoli. The fragility of the cells can result in many stripped nuclei in a granular background. The differential diagnosis occasionally can range from a benign or reactive process to features that are suspicious for malignancy. Some of the concerning cytologic features include necrosis, mitoses and nuclear pleomorphism.Methods:We identified 6 cases of suspected GCT on cytology within the last 10 years and compared them to their final histologic diagnoses.Results:Four had histologic correlation of GCT including one case that was suspicious for GCT on cytology and called atypical with features concerning for a malignant neoplasm. Of the other two cases where GCT was suspected, one showed breast tissue with fibrocystic changes, and the other was a Hurthle cell adenoma of the thyroid.Conclusions:These results imply that FNA has utility in the diagnosis of GCT, and should be included in the differential diagnoses when cells with abundant granular cytoplasm are seen on cytology. Careful attention to cytologic atypia, signs of reactive changes, use of immunohistochemistry, and clinical correlation are helpful in arriving at a definite diagnosis on FNA cytology.

Granular cell tumor in male breast masquerading as atypical apocrine neoplasm: A potential diagnostic pitfall in fine needle aspiration cytology

“…In FNAC, they have a moderately to highly cellular and monomorphic appearance, and the tumor cells are isolated to clustered, revealing poor cohesiveness. The granular cells have eccentrically located, round and bland nuclei and poorly defined cell borders with a “syncytial” pattern of aggregates, sometimes associated with distinct small nucleoli . High‐grade pleomorphism, macronucleoli and frequent mitoses are present in malignant cases, but they are extremely rare .…”

“…The unique appearance of their cytoplasm is due to an increased number of lysosomes. Those granules are diastase resistant and positive for PAS, S‐100 protein, and CD68 …”

“…Although GCT has a characteristic cytological appearance, it is sometimes of pitfall due to the overlap in cytomorphologic features between GCT and the entities included in their differential diagnosis, such as apocrine lesions from usual ductal hyperplasia with apocrine metaplasia to atypical apocrine hyperplasia or even apocrine carcinoma, as well as histiocytic reaction, frequently seen in conditions of fat necrosis, granulomatous inflammation and duct ectasia . Some rare epithelioid mesenchymal neoplasm may be also taken into consideration, and their cytomorphology and key features to be different from GCT are listed in Table . Besides, because the fragile cytoplasm of GCT is often dispersed in the background, it could also be mistaken for the necrosis commonly occurred in breast malignant tumor, or metastatic malignancy, such as renal cell carcinoma or melanoma .…”

Metastatic granular cell tumor to the breast diagnosed by fine needle aspiration cytology: A case report with review of the literature

“…1 They are characterized by granular, acidophilic cytoplasm that reflects the presence of secondary lysosomes, and thus stains strongly for S-100 protein and neuron specific enolase. 6 Malignant granular cell tumor (MGCT) is a well-established entity representing <1-2% of all GCT. 1,5,6 By convention, a GCT is considered malignant when a morphologically benign GCT metastasizes to regional lymph nodes or to distant sites.…”

“…6 Malignant granular cell tumor (MGCT) is a well-established entity representing <1-2% of all GCT. 1,5,6 By convention, a GCT is considered malignant when a morphologically benign GCT metastasizes to regional lymph nodes or to distant sites. 4 Fanburg-Smith et al assessed six histologic criteria to characterize MGCTs from their benign counterparts: necrosis, spindling, vesicular nuclei with large nucleoli, increased mitotic activity (>2 mitoses/10 high-power fields at ×200 magnification), high nuclear to cytoplasmic (N:C) ratio, and pleomorphism.…”