Section 9 -

Spindle Cell Lesions (Dr. Faquin) William C. Faquin, M.D., Ph.D. Celeste N. Powers, M.D., Ph.D.

Clinical History: A 48 year-old female presented with a 1.5 cm tender, rapidly enlarging lesion of the left parotid gland. An FNAB was performed. Cytologic Findings: The FNA is cellular and consists of many cytologically bland spindle cells with wispy tapered ends that are present singly and in loosely cohesive groups. Individual cells have oval nuclei, uniform fine chromatin, small inconspicuous nucleoli, and spindled cytomorphology reminiscent of fibroblasts. Mitotic activity is absent. A myxochondroid matrix and epithelial cells are not identified as might be expected in a salivary gland pleomorphic adenoma. Based upon these findings, the case was signed out as "spindle cell neoplasm, favor benign. The differential diagnosis includes nodular fasciitis, schwannoma, and myoepithelioma." The parotid lesion was excised; the spindle cells were positive for vimentin and actin, and negative for S-100, desmin, CD34, and keratin consistent with nodular fasciitis. Section 9 - Figure 1 Section 9 - Figure 2 Discussion: Nodular Fasciitis Nodular fasciitis is a reactive myofibroblastic proliferation that typically presents as a rapidly enlarging, often painful subcutaneous nodule. While uncommon in the head and neck region in adults, nodular fasciitis has been reported in most anatomic sites including the parotid gland. It is more common in young adults, age 20-40, and shows a predilection for the upper limb, especially the forearm. Nodular fasciitis is considered a pseudosarcomatous, benign process with a self-limiting clinical course; local recurrence is uncommon. Fine needle aspiration biopsies performed on cases of nodular fasciitis are characterized by the presence of numerous bland spindled cells with tapered ends, long wispy cytoplasmic processes, finely granular and evenly dispersed chromatin, and a small amount of vacuolated cytoplasm. The nuclei show some variation in size, and mitoses may be frequent. The cells are often arranged in small groups with intercellular collagen. Mitoses are often numerous, but the nuclei are never hyperchromatic or pleomorphic, helping to distinguish this reactive lesion from a true sarcoma. Cytologic Features of Nodular Fasciitis: Spindle-shaped fibroblasts: Bland oval to elongate nuclei Even chromatin/bland nuclear features Delicate cytoplasm Wispy bipolar cytoplasmic processes Cohesive groups with intercellular collagen Bloody and myxoid background Variable chronic inflammation Histologic Features of Nodular Fasciitis: Histologically, the nodular fasciitis exhibits short interweaving fascicles of spindled cells surrounded by many delicate thin-walled capillaries, extravasated red blood cells, and scattered inflammatory cells. The stroma is usually loose and collagenous with variable degrees of myxoid change, and occasional multinucleated giant cells may be present. In most cases of nodular fasciitis, the lesion is well circumscribed but unencapsulated. Immunohistochemical stains performed on cell block or biopsy material show that the spindled cells stain for vimentin and smooth muscle actin but not for S-100, desmin, keratin, or CD34. Ultrastructural studies demonstrate features of myofibroblastic differentiation. Section 9 - Figure 3 Nodular fasciitis showing bland spindled cells in a loose stroma and many capillaries with extravasated rbc's Differential Diagnosis of Salivary Gland-Associated Spindled Lesions: In the case presented here, the cytologic features are overall "benign-appearing" and therefore the differential diagnosis would include other reactive and benign neoplastic spindle cell lesions occurring in or near the region of the parotid gland. The differential diagnosis is quite broad but would include myoepithelioma/myoepithelial-predominant pleomorphic adenoma, schwannoma, fibrous histiocytoma, solitary fibrous tumor, and fibromatosis. The key to narrowing this differential diagnosis is to recognize the bland cytologic features of the spindled cells together with the myxoid background and inflammatory cells. Ancillary studies including an appropriate immunocytochemical profile and ultrastructural studies (as well as clinical correlation) are extremely useful in leading to a less generalized and more specific cytologic diagnosis, although a definitive diagnosis of nodular fasciitis may not always be possible and may require tissue biopsy. Immunomarkers for myoepithelial cells such as calponin among others will help to identify a myoepithelial-predominant tumor, and strong S-100 positivity is helpful for confirming a suspected schwannoma. Among the malignant spindle cell tumors that might be encountered in the parotid gland region are myoepithelial carcinomas, spindle variants of carcinoma ex pleomorphic adenoma, as well as MPNST, certain sarcomas, and metastatic tumors such as melanoma and spindle cell carcinoma. While it may not always be possible to give a specific diagnosis for a spindle cell lesion, it is usually possible to distinguish benign from malignant. Malignant spindle cell tumors are characterized by nuclear pleomorphism, hyperchromasia, atypical mitoses, prominent nucleoli, and background necrosis. With regard to mesenchymal tumors, variation in nuclear size and shape, together with a bland chromatin pattern, tends to be greater in pseudosarcomas while the nuclear chromatin is darker and more irregular in true sarcomas. In addition, true sarcomas generally lack the wispy cytoplasmic processes that characterize pseudosarcomas such as nodular fasciitis. The diagnosis of spindle cell lesions is challenging even in biopsy material. Therefore, caution is warranted in dealing with these lesions. Clinical information can be extremely useful in sorting out the nature of the lesion, and adequate material for special studies is always helpful. Because an FNA containing bland spindle cells can be quite difficult, especially when material for ancillary studies is limited, a note recommending close clinical follow-up and re-biopsy should the lesion fail to resolve or should it show evidence of growth, is suggested. This would be most appropriate for nodular fasciitis, which is expected to resolve spontaneously. Differential Diagnosis of Benign and Malignant Spindle Cell Lesions: Benign: Myoepithelioma Schwannoma Nodular Fasciitis Leiomyoma Fibromatosis Malignant: Myoepithelial carcinoma Carcinoma ex PA Melanoma MPNST Spindle cell carcinoma Fibrosarcoma MFH Section 9 - Figure 4 Cellular Pleomorphic Adenoma Section 9 - Figure 5 Schwannoma Section 9 - Figure 6 Spindle Cell Carcinoma