Benign Metastasizing Pleomorphic Adenoma of Salivary Gland: Diagnosis of Bone Lesions by Fine-Needle Aspiration Biopsy Martha Bishop Pitman, M.D.,Ann D. Thor, M.D.,Max L. Goodman, M.D., and Andrew E. Rosenberg, M.D

Two cases of benign salivary gland pleomorphic adenomas metastatic to bone (benign-metastasizingpleomorphic adenomas) diagnosed byjine-needle aspiration biopsy are presented. Both primary tumors were slightly atypical cytologically but neither case demonstrated features of carcinoma. The metastatic lesions contained benign epithelial, myoepithelial, and stromal components. In both cases the clinical history was either not known by the radiologist or not communicated to the cytopathologist interpreting the case, and a primary tumor of bone was the leading clinical diagnosis. Obtaining pertinent clinical history and comparing the cytomorphology of the bone aspirate with the primary parotid tumor allowed f o r an accurate diagnosis in both cases. The differential diagnosis with primary bone tumors is discussed and the importance of clinical history is emphasized. Diagn Cytopathol 1992; 8:384-387. @ 1992 Wiley-Liss, Inc

not provided to the cytologist. Tumors with myxoid or cartilagenous components aspirated from a bone lesion can easily be mistaken for a primary bone tumor under these conditions. The FNA cytomorphology of pleomorphic adenomas has been well described. 5,6 However, the cytologic features of only one BMPA metastatic to the lung diagnosed by FNA has been reported. The clinical, radiologic, and cytologic features of two BMPA metastatic to bone are described and the differential diagnosis and importance of pertinent clinical information is discussed.

Key Words: Pleomorphic adenoma; Bone metastases; Fine-needle aspiration

A 70-year-old female presented with a 3 year history of a mass in the right soft palato-pharynx. A computerized tomographic (CT) scan of the nasopharynx revealed a large parapharyngeal mass involving the deep lobe of the parotid. A laryngoscopic biopsy revealed a pleomorphic adenoma. It was resected except for a small focus of tumor adjacent to the base of the skull. The histopathologic examination demonstrated a pleomorphic adenoma with myxoid areas, epithelial clusters, and focal myoepithelial proliferation in nests and scattered around epithelial ducts (Fig. 1). Although neither cellular anaplasia nor an infiltrative pattern were identified, there was focal cellular atypia with occasional mitoses, and focal necrosis (Fig. 1, inset). Seventeen months after surgery the mass recurred locally and chest roentgenograms demonstrated bilateral, multiple small lung nodules consistent with metastatic disease. Radiation therapy eliminated all radiologic and clinical evidence of localized disease, and the patient remained asymptomatic with pulmonary lesions. Generalized malaise and right lower quadrant pain developed 2% years later. Physical examination revealed a large palpable, tender, lobulated mass just above the right inguinal

Benign metastasizing pleomorphic adenoma (BMPA) is an extremely rare tumor in which a cytologically benign pleomorphic adenoma (usually of major salivary gland origin) metastasizes as such. The metastatic tumor is composed of benign epithelial and stromal elements histologically identical to the primary tumor. With the increasing utilization of fine-needle aspiration biopsy (FNA) techniques by radiologists, we have diagnosed two of these rare tumors metastatic to bone in less than 1 year. Our experience suggests that because of the rarity of this lesion, radiologists and clinicians often fail to suspect a metastatic lesion from a typically benign salivary gland tumor, and, as a result, pertinent clinical history is often 's4

Received August 30, 1991. Accepted November 11, 1991. From the Department of Pathology, Massachusetts General Hospital, Harvard Medical School and Department of Pathology, Massachusetts Eye and Ear Infirmary, Boston, MA. Address reprint requests to Martha Bishop Pitman, M.D., Department of Pathology, Massachusetts General Hospital, Boston, MA 02 114.

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Case History Case I

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FNA DIAGNOSIS O F BMPA

Fig. 1. Case 1: Histomorphology of the primary parotid gland pleomorphic adenoma. Epithelial nests and ducts, and myoepithelial cells embedded in a myxoid stroma (hematoxylin and eosin, x 125). There were foci of cellular atypia with mitoses and individual cell necrosis (inset, x 500).

Fig. 2. Case 1: CT of the pelvis showed a large lytic lesion destroying the ilium and forming an adjacent soft tissue mass.

area. An abdominal and pelvic CT scan (Fig. 2 ) demonstrated a 3.5 cm mass involving the right iliacus muscle and iliac bone. Radiologically, the mass appeared to arise from the iliac bone and extend into the soft tissue, therefore a primary bone tumor was suspected. An FNA biopsy of the iliac mass was performed with a 21 gauge needle under CT guidance. The clinical history of a prior salivary gland tumor as well as the existence of metastatic pulmonary disease was not known by the radiologist or the cytopathologist. Case 2

A 63-year-old male had a right parotidectomy for a pleomorphic adenoma and subsequently underwent multiple

Fig. 3. Case 2: Histomorphology of the primary parotid gland pleomorphic adenoma. A monomorphic population of rounded myoepithelial cells in a myxoid stroma (hematoxylin and eosin, x 125). Foci of cells with irregular nuclear features but no malignant characteristics or mitoses were present (inset, x 788).

resections and radiation therapy for recurrent tumor. He presented to our hospital 40 years following his initial parotid tumor resection with another local recurrence. This mass was radically resected and post-operative radiation therapy was administered. The tumor recurred again and was resected 1 year later. The histomorphology of the parotid gland pleomorphic adenoma demonstrated predominantly myxoid areas with spindled to rounded myoepithelial cells (Fig. 3) and focally cellular areas with irregular nuclear features but without characteristics of malignancy or increased mitotic activity (Fig. 3, inset). After a 2 year loss to follow-up, the patient presented with a 6 month history of lower back pain. Chest roentgenograms showed bilateral pulmonary nodules in the left lower lung. CT scan demonstrated a first lumbar vertebral mass with extension into the right paravertebral soft tissue which was biopsied using CT guidance and FNA techniques (Fig. 4). The specimen was sent to the cytology laboratory without clinical history.

Cytomorphology Case I. The rapid hematoxylin and eosin stained smears prepared immediately after aspiration were moderately cellular. Both epithelial and stromal components were present with a background of fine, slightly basophilic myxoid ground substance in which numerous myoepithelial cells were noted (Fig. 5). The epithelial component consisted of numerous, occasionally very large, two dimensional sheets of small bland appearing cells with round to oval nuclei. There was a finely granular, evenly distributed chromatin pattern with an occasional nuclear groove and inconspicuous nucleolus (Fig. 5 , inset). The Papanicalaou stained smears demonstrated a basophilic Diagnostic Cytopathology, Vol 8, No 4

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~ i 4. ~case . 2: CT of the lumbar vertebrae illustrated the properly placed needle in the destructive lesion during fine-needle aspiration bi-

Fig. 6 . Case 1: Cell block preparation of the fine-needle aspirate. Small fragment of tissue with cellular features resembling the patient's primary Parotid gland tumor (hematoxY1in and eosin, x 2oo).

OPSY.

Fig. 5. Case 1: FNA smear of the ilia1 lesion. Cellular epithelial and myoepithelial groups adjacent to myxoid stroma embedded with cells (hematoxylin and eosin, rapid stain, X 125). The epithelial cells were bland with inconspicuous nucleoli and occasional nuclear grooves (inset, X 788).

staining quality to the myxoid mucopolysaccharide background; however, air dried May-Griinwald-Giemsa stained cytospin preparations best illustrated a brightly eosinophilic stromal component. H & E stained sections of the cell block demonstrated an architecture which recapitulated the histomorphology of the primary salivary gland tumor (Fig. 6 ) . Case 2. The Papanicalaou stained cytospin preparations (smears were not prepared) were relatively paucicellular compared to Case 1. There were a few cellular groups with a scant myxoid stroma (Fig. 7). The cells were small, rounded, monomorphic, and slightly spindled with round to oval somewhat pleomorphic and hyperchromatic nuclei 386

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Fig. 7. Case 2 : FNA biopsy of vertebrae (cytospin). Cellular aggregates of small, monomorphic round to slightly spindled cells interspersed in a scant myxoid stroma (Papanicolaou, x 313). Slight nuclear pleomorphism and hyperchromasia was present but there were no mitoses or necrosis (inset, X 788).

without prominent nucleoli. The cytoplasm was scant and indistinct. No mitoses were present and there was no necrosis (Fig. 7, inset). An intact tissue core was processed as a cell block which showed an architectural pattern resembling the histomorphology of the original parotid tumor (Fig. 8). The epithelial cells formed nests and sheets which focally contained scant myxoid stroma. Hyperchromasia, pleomorphism, and mitotic figures were not identified.

Discussion We report two cases of BMPA metastatic to bone. Metastases of BMPA contain the same benign appearing epithelial and stromal elements as the primary tumors. This

FNA DIAGNOSIS OF BMPA

Fig. 8. Case 2: Cell block preparation of FNA of the vertebrae. Intact tissue fragment with rounded to spindled myoepithelial cells in a myxoid stroma resembling the patient’s primary parotid tumor (hematoxylin and eosin, ~ 5 0 0 ) .

entity differs from the much more common carcinoma ex-pleomorphic adenoma, i.e., carcinoma arising in a pleomorphic adenoma, which accounts for 99% of metastasizing pleomorphic adenomas and, cytologically, is composed of malignant epithelial elements without stroma. The malignant mixed tumor, a very rare carcinosarcoma, contains both malignant epithelial and stromal elements in primary and metastatic lesions.’ Bone and lung are common sites for metastases of all three variants of pleomorphic adenoma that metastasize. 2,3,10 The first accepted case of a BMPA was reported by Foote and Frazell in 1954.’ Others have subsequently been reported 24 and only one case has been diagnosed by FNA. As with the two cases reported here, most metastasize from primary tumors of the parotid gland. Many of the primary tumors described in the literature which subsequently metastasized as BMPA demonstrated infiltrative tumor borders and an increase in mitotic activity. These features in an otherwise typical pleomorphic adenoma of the salivary gland, particularly with a history of multiple recurrences, suggest a biologically aggressive tumor capable of distant metastases. In our cases, only case 1 demonstrated increased mitotic activity in the primary tumor and neither had infiltrative borders. It has been suggested that tumor fragmentation during surgical excision with vascular seeding may help generate metastases. ” For these reasons, wide excision without tumor disruption is recommended. The radiologic findings were consistent with an invasive, destructive tumor arising from the ilium in case 1 and vertebral body in case 2. Radiologically, the differential diagnoses included chondrosarcoma and malignant fibrous histiocytoma (MFH). Cytologically, the differential diagnosis was between a myxoid MFH and a dedifferen-



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tiated chondrosarcoma. The latter was considered because of the cellular aggregates of spindled myoepithelial cells prominent in both cases but was ruled out by the relatively bland nature of the nuclei and the lack of mitoses. A myxoid MFH could produce a strikingly similar cytomorphologic picture with a myxoid background and bland appearing oval to spindled cells; however, the characteristic “chicken wire” vascular pattern so often apparent on FNAs of myxoid MFHs was not evident in either case. I n case 1, air dried smears with MGG showed wispy, highly eosinophilic stroma characteristic of salivary gland pleomorphic adenomas; hence the medical history was reviewed. In case 2, the medical history was reviewed as a result of our experience with the first case. The single most important factor to establishing a definitive diagnosis in BMPAs is the clinical history. In both cases the previous salivary gland tumor histology was compared to the tumor cytomorphology on FNA and a confident diagnosis was made. Even without the slides for comparison, however, a clinical history of pleomorphic adenoma, particularly one with noted histomorphologic atypia and multiple recurrences, would be sufficient to diagnose a BMPA.

Acknowledgment The authors would like to sincerely thank Ms. Joyce Cheatham for her expert secretarial assistance, and Ms. Michelle Forrestall and Mr. Steve Conely for their excellent photographic assistance.

References 1. Foote FW, Frazell FL. Tumors of the major salivary glands. In: Atlas of tumor pathology, fascicle 11. Washington, DC: Armed Forces Institute of Pathology, 1954. 2. Chen KTK. Metastasizing pleomorphic adenoma of the salivary gland. Cancer 1978;42:2407-2411. 3. Gerughty RM, Scofield HH, Brown FM, Hennigar GR. Malignant mixed tumors of salivary gland origin. Cancer 1969;24:471 4 8 6 . 4. Young GR, Sheuer PJ. Histologically benign mixed parotid tumor with hepatic metastasis. J Pathol 1973;109:171-173. 5 . Eneroth CM, Franzen S, Zajicek J. Cytologic diagnosis on aspirates from 1000 salivary gland tumors. Acta Otolaryngol [Suppl] (Stockh) 1967;224:168-17 1. 6. Eneroth CM, Zajicek J. Aspiration biopsy of salivary gland tumours: 111. Morphologic studies on smears and histologic sections from 368 mixed tumors. Acta Cytol (Baltimore) 1966;10:440-454. 7. Landolt U, Zobeli L, Pedio G. Pleomorphic adenoma of the salivary glands metastatic to the lungs: diagnosis by fine-needle aspiration cytology. Acta Cytol (Baltimore) 1990;34:101-112. 8. Tortoledo ME, Luna MA, Batsakis JG. Carcinoma ex pleomorphic adenoma and malignant mixed tumor. Arch Otolaryngol 1984;llO: 172-176. 9. Batsakis JG. Malignant mixed tumor. Ann Otol Rhino1 Laryngol 1982;91:342-343. 10. Moberger JG, Eneroth C-M. Malignant mixed tumors of the major salivary glands. Cancer 1968;21:1198-1211. 11. Thackray AC, Lucas RB. Tumors of the major salivary glands. In: Atlas of tumor pathology, Fascicle 10, second series. Washington, DC: Armed Forces Institute of Pathology, 1974. Diagnostic Cytopathology, Vol 8, No 4

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Benign metastasizing pleomorphic adenoma of salivary gland: diagnosis of bone lesions by fine-needle aspiration biopsy.

Two cases of benign salivary gland pleomorphic adenomas metastatic to bone (benign-metastasizing pleomorphic adenomas) diagnosed by fine-needle aspira...
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