Spindle Cell Neoplasm of the Thoracic Spine Mark A. Arnesen, MD, and John W. Jones, MD The case is a 56-year-old woman who presented with cord compression from a lesion of the thoracic spine. Histologic analysis confirmed the diagnosis of a spindle cell sarcoma. Ultrastructural analysis showed features characteristic of a leiomyosarcoma. Subsequent discussion with the patient revealed a history of hysterectomy performed for fibroid uterus 5 years before the current presentation. Review of the previous surgical specimen confirmed the presence of a leiomyosarcoma originally interpreted as a large infarcted myoma.

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Department of Pathology/lll36, Abbott Northwestern Hospital, 800 E 28th Street, Minneapolis, Minnesota 55407, USA

KEY WORDS: leiom yosarcoma, mitotic activity, smooth muscle tumor of uncertain malignant potential, uterus.

CLINICAL HISTORY A 56-year-old woman was admitted for conservative medical management of severe bilateral leg pain with mildly decreased sensation in the right 1-5 dermatome, which was believed to be secondary to a herniated intervertebral disc. Computed tomography of the lumbar spine revealed mild to moderate central canal stenosis in 14-5 due to disc bulge and facet thickening with borderline distortion of the 1-5 nerve root. After several days of bed rest, the patient developed numbness of the lower extremities below the knees and bilateral foot drop. Magnetic resonance imaging of the cervical and thoracic spine revealed a large destructive soft tissue mass involving the posterior elements at T- I I and T12, extending into the posterior spinal canal, and compressing the distal thoracic cord and roots posteriorly: A laminectomy was performed, revealing a large globular mass that seemed to be centered around the T I I- 12 spinous processes. The tumor displaced surrounding muscle and ___ _

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Address correspondence to M A Arnesen

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infiltrated around and through the lamina of T- I I and T- 12, extending into bone in an erosive fashion. It was the impression of the neurosurgeon that the tumor arose from the T-1 I nerve root. The tumor was subtotally resected in pieces and submitted for histologic analysis. Frozen section was performed, and a diagnosis of sarcoma vs nerve sheath tumor with pleomorphic giant cells and necrosis was rendered.

PATHOLOGIC FINDINGS

Light Microscopy The tumor was a cellular pleomorphic spindle cell neoplasm with extensive areas of coagulative necrosis and an invasive pattern extending between bony trabeculae into adjacent soft tissues. It was cornposed of interlacing fascicles and bundles of polymorphous spindle cells with hyperchromatic nuclei ranging from relatively uniform, elongated, cigar-shaped forms to polymorphous giant cells with macronucleoli. The cytoplasm of the neoplastic _ cells was elongated and eosinophilic with a wispy character (Fig. 1 ) .

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M. A. Arnesen and J. W. Jones

cles along their cytoplasmic membranes. Myofilaments were plentiful at least focally in most tumor cells, and many cells exhibited peripheral densities (Figs. 2 and 3).

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COMMENTS This case presented as a spindle cell sarcoma, which clinically was thought to be a primary neurogenic sarcoma. Immunohistochemical evaluation did not support a neurogenic origin in view of the negative staining for S-100 protein. The characteristic electron microscopy features as well as immunostaining for vimentin and desmin were held to be diagnostic of a leiomyo ~ a r c o m a .Although ~ a primary leiomyosarcoma certainly could present in this location, the possibility of metastasis from

FIG. 1 Metastatic spindle cell neoplasm in thoracic spine. Most of this tumor was composed of a polymorphous spindle cell proliferation with scattered mitotic figures. Hematoxy/in and eosin (H&E), x 200.

Immunohistochemistry The tumor samples were fixed primarily in Omnifix (Xenetics Biomedical, Irvine, California).’ They were stained with commercial kits (Biogenex Laboratories, San Ramon, California) b y means of the peroxidase-antiperoxidase technique with 3-amino-9-ethylcarbazole for vimentin,’ d e ~ m i nand , ~ S-I00 p r ~ t e i nThe . ~ neoplastic cells were strongly positive for vimentin. weaklv oositive for desmin. and neaati& for s - ~ O Oprotein. 1

Electron Microscopy The tumor cells were pleomorphic and contained variable numbers cytoplasmic organelles. Many cells were invested in basal lamina and exhibited pinocytotic vesi-

FIG. 2 Primary uterine leiomyosarcoma. This tumor exhibited extensive necrosis but did contain areas of viable spindle cell tumor morphologically identical to the metastatic thoracic spine lesion. H&E,

x 200.

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FIG. 3 Electron microscopy of thoracic spine metastasis. Tumor cells were invested in basal lamina with scattered pinoc ytotic vesicles. M yo filaments with dense bodies were readily found in the majority of neoplastic cells, x 31,867.

an occult primary was strongly considered clinically. Subsequent discussion with the oncologist and house staff led to the suggestion that a pelvic examination (not documented in the preoperative evaluation) was certainly indicated. A t this point, discussion with the patient revealed that a hysterectomy had been performed for a fibroid uterus 5 years earlier at another institution. Review of the surgical pathology report from this previous hysterectomy indicated the presence of an 8-cm circumscribed mural nodule with a necrotic, pinkish-tan cut surface that was interpreted as a large infarcted myoma. Subsequent review of the slides from this largely necrotic smooth muscle tumor revealed a peripheral viable rim of a highly cellular neoplasm composed of spindle cells with pleomorphic hyperchromatic

nuclei (Fig. 4). Examination of many fields of the tumor revealed that it was predominantly without mitoses. Focally there was a mitotic rate of at most 5 mitoses per 10 high-power fields. On the basis of its subsequently proven metastatic potential, this uterine smooth muscle tumor was held t o be best classified as a leiomyosarcoma. Subsequent radiologic and clinical evaluation revealed no additional evidence of disease. The patient underwent a course of radiotherapy t o the thoracic spine (4500 rads t o T9-L2) and remains alive and well with no evidence of disease 6 months after surgery. This case points out several important clinical and pathologic aspects of both metastases from unknown primary sites and uterine smooth muscle neoplasms. Electron microscopy and immunohisto-

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M. A. Arnesen and J. W. Jones

FIG. 4 Same as Fig. 3; ~31,867. chemistry played a crucial role in determining the correct diagnosis in a case that clinically was believed t o represent a primary neurogenic malignancy. Once the correct diagnosis was established, a thorough history and physical evaluation were performed; these had been lacking in the previous focused evaluation of this patient’s clinical symptoms. It seems ironic that electron microscopy prompted a complete history and physical examination in the diagnostic process. Finally, the malignant biologic behavior of this uterine smooth muscle neoplasm belied this somewhat ambiguous histology. Distinguishing between benign leiomyomas and leiomyosarcoma has always proven difficult. Taylor and Norris,‘ in a series of 63 uterine smooth muscle tumors, used the criterion of mitotic activity t o distinguish benign from malignant lesions in lesions with fewer than 10 mitoses per 10 high-power fields behaving in a clinically benign fashion and in lesions with 10 or more mitotic figures per 10 high-power fields behaving in a clinically malignant fashion with recurrence or metastasis. In their experience, cellular atypism did not

correlate well with survival. Kempsen and Bari’ hold that invasion of contiguous organs or blood vessels connotes a malignant prognosis in lesions with fewer than 5 mitoses per 10 high-power fields behaving in a benign fashion; in lesions with 5 t o 9 mitoses per 10 high-power fields placed in an uncertain, potentially malignant category; and in lesions with more than 10 mitoses per 10 high-power fields behaving in a malignant fashion. Burns et aI8 arrived at a cut-off of 5 mitoses per 10 high-power fields for malignant lesions but described a malignant course in some cases with fewer than 5 mitoses per 10 high-power fields. Silverberg’ states that an infiltrating margin is associated with a malignant clinical course and that a circumscribed margin is associated with a benign course. Barter et al,” however, found that lesions with atypia and 5 t o 9 mitoses per 10 high-power fields or lesions with more than 10 mitoses per 10 high-power fields were associated with a malignant course and stated that menopausal status, circumscription of tumor margin, tumor size, and vascular invasion were not associated with an unfavorable prognosis.

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With this conclusion in the literature, it finement of diagnostic criteria, these leis not surprising that some have tried to sions continue to be a challenging problem use ancillary techniques such as DNA for surgical pathologists, as illustrated by ploidy as elucidated by flow cytometry to our example. determine prognosis. In a recent series of The prognosis of overt leiomyosarcoma this kind,” although benign leiomyomas with 10 or more mitotic figures per 10 were found to be more likely to have a dip- high-power fields remains unfavorable; a loid pattern (99%) than leiomyosarcomas 17% 5-year survival rate was reported re(28%),this feature could not be used as cently in a series of 106 patients. l4Neither an absolute diagnostic criterion in any indi- adjuvant ~ h e m o t h e r a p ynor ’ ~ treatment for vidual case. recurrent disease16 has shown impressive Several recent reports have further re- response rates. Even experimental protofined diagnostic criteria for uterine smooth cols that use agents such as E t ~ p o s i d e ’ ~ muscle tumors. In the series of Perrone have shown only objective response rates and Dehner,” unfavorable prognostic fea- of 10.7%. tures were described in mitotically active smooth muscle tumors; these features included postmenopausal status, a clinical or CONCLUSIONS intraoperative impression of cancer on the This patient developed a thoracic spine part of the surgeon, extension of the tu- metastasis from a uterine leiomyosarmor beyond the uterine corpus, tumor size coma, the diagnosis being established by greater than 10 cm, marked cytologic electron microscopic examination of the atypia, invasive borders, necrosis, and mi- metastatic lesion. The primary site for this totic counts exceeding 20 mitoses per 10 metastatic lesion was found after review high-power fields. These investigators of the original pathologic material. Applicastate that there is a category of prognosti- tion of the criteria of Kempson and Hencally favorable, mitotically active smooth d r i c k ~ o nallowed ’~ correct classification of muscle tumors that may have mitoses in this primary uterine smooth muscle tumor the range of 5 to 15 mitoses per 10 high- on the basis of up to 5 mitoses per 10 power fields when the above described un- high-power fields in a highly cellular neofavorable prognostic features are lacking. plasm with anaplasia and tumor necrosis. Kempson and H e n d r i ~ k s o n ’have ~ described morphologic features that lower the threshold of 10 mitotic figures per 10 REFERENCES 1. Quinn B. Rapid microwave fixation with cryohigh-power fields for leiomyosarcoma; protectants for surgical pathology. Lab Invest. these include intravascular growth, tumor 1989;60:75A. Abstract. cell necrosis, myxoid stroma, abnormal mi2. Denk H, Krepler R, Artlieb U, et al. Proteins of totic features, epithelioid histology, and anintermediate filaments. A n immunohistochemiaplasia as defined by atypia, hyperchromacal and biochemical approach t o the classification of soft tissue tumors. Am J Pathol. 1983; sia, and pleomorphism. They further define 1 10: 1 93-208. criteria for leiomyoma with increased mi3. Gabbiani G, Kapanci Y, Barazzone P, Franke totic counts. These neoplasms have the WW. lmmunochemical identification of intercellularity and cytology of normal myomemediate sized filaments in human neoplastic trium and between 5 and 15 mitotic figcells. A diagnostic aid for the surgical pathologist. Am J Pathol. 1981;104:206-216. ures per 10 high-power fields. They en4. Nakajima T, Watanbe S, Sat0 Y, Kameya T, courage close examination and extensive Hirota T, Shimosato Y. An immunoperoxidase sectioning (one section per centimeter of study of S-100 protein distribution in normal tumor) for tumors with hypercellularity, cyand neoplastic tissues. Am J Surg Pathol. 1982;6:715-727. tomegaly, ambiguous differentiation, pecu5. Mackay B, Ro J, Floyd C, Ordonez NG. Ultraliar gross appearance (soft, hemorrhagic, structural observations on smooth muscle tumyxomatous, infiltrative, necrotic, or othmors. Ultrastruct Pathol. 1987; 1 1:593-607. erwise peculiar looking), and clefts around 6. Taylor HB, Norris HJ. Mesenchymal tumors of the uterus. Arch Pathol. 1966;82:40-44. smooth muscle nodules. In spite of this re-

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34 7. Kempson RL, Bari W. Uterine sarcomas: classification, diagnosis and prognosis. Hum Pathol. 1970;1:331-349. 8. Burns B, Currey RH, Bell MEA. Morphologic features of prognostic significance in uterine smooth muscle tumors: a review of eightyfour cases. Am J Obstet Gynecol. 1979;135: 109-1 14. 9. Silverberg SG. Leiomyosarcoma of the uterus. Obstet Gynecol. 1971;38:613-628. 10. Barter JF, Smith EB, Szpak CA, Hinshaw W, Clarke-Pearson DL, Creasman WT. Leiomyosarcoma of the uterus: clinicopathologic study of 21 cases. Gynecol Oncol. 1985;21:220-227. 1 1. Tsushima K, Stanhope CR, Gaffey TA, Lieber MM. Uterine leiomyosarcomas and benign smooth muscle tumors: usefulness of nuclear DNA patterns studied by flow cytometry. Mayo Clin Proc. 1988;63:248-255. 12. Perrone T, Dehner LP. Prognostically favorable "mitotically active" smooth-muscle tumors of the uterus. Am J Surg Pathol. 1988; 12: 1-8.

M. A. Arnesen and J. W. Jones 13. Kempson RL, Hendrickson MR. Pure rnesenchymal neoplasms of the uterine corpus: selected problems. Semin Diagn Pathol. 1988;5: 172-1 98. 14. Larson B, Silfversward C, Nilsson 6,Pettersson F. Prognostic factors in uterine leiomyosarcoma: a clinical and histopathological study of 143 cases. Acta Oncol. 1990;29:185-191. The Radiumhemmet series, 1936- 198 1 . 15. Hannigan EV, Freedman RS, Rutledge FN. Adjuvant chemotherapy in early uterine sarcoma. Gynecol Oncol. 1983;15:56-64. 16. Berchuk A, Rubin SC, Hoskins WJ, Saigo PE, Fierce VK, Lewis JL. Treatment of uterine leiomyosarcoma. Obstet Gynecol. 1988;71: 845-850. 17. Slayton RE, Blessing JA. Angel C, Berman M. Phase II trial of Etoposide in the management of advanced and recurrent leiornyosarcorna of the uterus: A gynecologic oncology group study. Cancer Treat Rep. 1987;71: 13031304.

Spindle cell neoplasm of the thoracic spine.

The case is a 56-year-old woman who presented with cord compression from a lesion of the thoracic spine. Histologic analysis confirmed the diagnosis o...
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