Leiomyosarcoma of the Orbit: Diagnosis of Its Recurrence by Fine-Needle Aspiration Cytology Dilip K. Das, M.D., Ph.D., Jayachandra Das, M.D., Dileep Kumar, M.SC., Ph.D., Naveen C. Bhatt, B.SC. (MLT), Kiran Banot, M.s., and Radha Natarajan, M.S.

A n 8Y2-yr-old boy with proptosis was diagnosed to have low-grade leiomyosarcoma of the orbit following lateral orbitotomy and his- tology of an incompletely excised intraconal mass. He received chemotherapy but had recurrence ofproptosis at the age of 12 yr. Ultrasonography revealed a solid mass and its fine-needle aspira- tion cytology features were consistent with recurrence of leiomyo- sarcoma. A year later, the cytodiagnosis was confirmed by histol- ogy of the excised tumor from a second lateral orbitotomy. Masson’s trichrome stain confirmed the smooth muscle nature of the neoplasm and ultrastructural features were in favor of leio- myosarcoma. The patient received intermittent chemotherapy, and i,s clinically free from disease at the age of 17 yr. Diagn Cytopathol 1992;8:609-613. 0 1992 wiley-Liss, Inc.

Key Words: Proptosis; Cytodiagnosis; Orbitotomy

Sarcomas of the orbit are rare neoplasms except for rhab- domyosarcoma, which is the most common malignant mesenchymal orbital neoplasm. ‘ g 2 Although there have been a few publications on fine-needle aspiration cytology (FNAC) diagnosis of rhabdomyosarcoma and unspecified sarcoma, 3-5 to the best of our knowledge there is no report on FNA diagnosis of leiomyosarcoma of the orbit. In the present communication we describe a case of recurrent leiomyosarcoma of the orbit which was diagnosed by FNAC and the cytodiagnosis was subsequently recon- firmed histologically, histochemically, and by ultrastruc- tural studies.

Case Report A 12-yr-old boy with recurrent proptosis of the right eye and ultrasonographic evidence of an intraconal solid mass

Received October 2, 1991. Accepted February 28, 1992. From the Institute of Cytology and Preventive Oncology (ICMR) and

the Department of Ophthalmology, Maulana Azad Medical College, New Delhi, India.

Address reprint requests to Dr. Dilip K. Das, Department of Pathol- ogy, Faculty of Medicine, Kuwait University, P.O. Box 24923, Safat, 13110 Kuwait.

was sent for FNAC in January 1987. A look into his past history revealed that the boy first came to the eye outpa- tient department of Guru Nanak Eye Centre, Maulana Azad Medical College, New Delhi, India, at the age of 8% yr with progressive painless proptosis in his right eye for 3% yr, more rapidly growing for the last 6 mo following a blunt injury. This was associated with a diminution of vision. On examination, the patient had proptosis and the affected eye had a vision of 6/36. After admission, the patient underwent a lateral orbitotomy. In the apical re- gion an intraconal mass which appeared to be capsulated but protruded out of the muscle into the medial part was discovered. Since it was very friable it could not be excised completely. The histopathological report was leiomyosar- coma of low-grade malignancy.

Chemotherapy was started 3 weeks later which was comprised of cycles of vincristine (oncovin), cyclophos- phamide (endoxan), and doxorubicin hydrochloride (adriamycin). His vision returned to 6/6. Chemotherapy was stopped after 1 yr following cardiotoxic effects. The patient apparently remained well for 2% yr, after which the proptosis recurred (Fig. 1) and the patient was sent for FNAC.

FNAC was performed from the upper and nasal quad- rant of the right orbital cavity with a 22-gauge disposable needle and 20-ml disposable syringe fitted with Franzen’s syringe pistol after retracting the upper eyelid and rotating the eyeball laterally and inferiorly. The needle was di- rected toward the apex. No local anesthesia was used. Aspirated material was comprised of blood and small tis- sue fragments. Air-dried smears made from the aspirated material were May-Griinwald-Giemsa (MGG) stained. The smears showed groups of tumor cells with elongated (cigar-shaped) nuclei and ill-defined cytoplasmic outline arranged in a haphazard manner (Fig. 2A) . However, in some areas arrangement of tumor cells in the form of bundles or fascicles and nuclear palisading was noticed

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Fig. 1. The 12-yr-old patient with recurrent proptosis, 3% yr after diagnosis of orbital leiomyosarcoma following lateral orbitotomy and histology.

(Fig. 2B). Cytomorphological features were consistent with recurrence of leiomyosarcoma.

Following cytodiagnosis and certain baseline investiga- tions, cyclophosphamide (endoxan) was given. Since the tumor persisted, a second lateral orbitotomy was per- formed 1 yr later. Besides routine hematoxylin-eosin stain- ing the sections were stained with reticulin, Masson’s tri- chrome, and phosphotungstic acid hematoxylin (PTAH). Histopathological examination of the excised mass re- vealed a tumor composed of intertwining bundles of spin- dle-shaped tumor cells (Fig. 3A). The nuclei of the tumor cells were elongated in longitudinal section and round to oval in cross section. In some areas the nuclei were plump and had irregular outline and distinct nucleoli (Fig. 3B). Mitotic count revealed 1-2 mitotic figures per 10 high power fields (Fig. 3C).

With the reticulin stain, abundant reticulin fibers were observed. These fibers were wrapped around individual cells and were irregularly distributed (Fig. 4A ). The tumor cells stained red with acid fuchsin in Masson’s trichrome stain (Fig. 4B). PTAH stain did not reveal any cross striations.

By transmission electron microscopy (Fig. 5A and 5B), the cells showed fine filaments mostly located at the pe- ripheral part of the cytoplasm and a large number of focal densities. There was relative paucity of pinocytotic vesi- cles on the cytoplasmic side of the external lamina which itself was not so well developed. The nuclei had irregular shape and there was condensation of granular chromatin along the nuclear membrane.

Following the second orbitotomy, chemotheraphy com- prising vincristine (oncovin), actinomycin D, and cyclo- phosphamide (endoxan) was started in July 1989 and con- tinued in cycles for 6 mo. In June 1990, chemotherapy was repeated and completed in 3 mo. The patient was dis- charged with a vision of 6/6. The patient is now 17 yr old

Fig. 2. (A) FNA smear from orbital mass. Tumor cells having elongated nuclei with blunt end, haphazardly arranged (MGG, ~400). (B) Ar- rangement of tumor cells in the form of fascicle showing nuclear palisad- ing (MGG, x 160).

and is followed up in the outpatient department. There is no increase in proptosis and the vision is still maintained at 6/6.

Discussion Leiomyosarcoma of the orbit is an extremely rare neo- plasm. The first case was reported by Terry6 in 1934 but during the next four decades no other case came to light except that reported by Begue and Mawas.’ While de- scribing orbital neoplasms Hogan and Zimmerman wrote that it was theoretically possible for leiomyoma and leiomyosarcoma to arise in the orbit since it contains smooth muscle, but the authors themselves had not recog- nized any orbital neoplasm of smooth muscle origin. Yan- off and Fine2 even felt that leiomyosarcoma probably did not occur in the orbit. However, between 1972 and 1988, six more cases were reported. ‘-12 In addition, there were cases which followed radiation therapy for retinoblasto-

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Fig. 3. (A) Section from excised specimen of recurrent leiomyosarcoma of the orbit. Tumor composed of intertwining bundles of spindle-shaped cells (H&E, X 160). (B) Higher magnification of recurrent leiomyosar- coma showing spindle-shaped tumor cells with plump cigar-shaped nu- clei and nuclear irregularity (H&E, X 400). (C) Mitotic figure (arrow) in the tumor (H&E, X 640).

ma. I 3 , l 4 Therefore, the present case is probably the ninth one in the literature where there was no past history of radiation therapy.

According to Meekins et al., l 2 leiomyosarcoma of the orbit typically occurs in older female patients and has a high incidence of distant metastasis. The age of the six cases of leiom yosarcomas reviewed by these authors and the case reported by them ranged from 36 to 82 yr with a median of 5 2 yr. Our patient, who was 8% yr old when he first reported in the hospital and who had a history of proptosis for 3% yr, appears to be the youngest case in the literature. The only other case of leiomyosarcoma of the orbit in young age was that of a 7-yr-old girl reported by Beague and Mewas. ’ Jakobiec et al., however, feel that this could be an embryonal rhabdomyosarcoma.

Fig. 4. (A) Section of leiomyosarcoma showing rich reticulin network. Fibers are wrapped around individual cells and show irregular distribu- tion (reticulin, X 160). (B) Red staining of cytoplasm of tumor cells (Masson’s trichrome, x 160).

Imaging modalities like ultrasonogram and CT scan- ning have been utilized to determine the precise location of the tumor in the orbit l 2 and even the possible pathology has been predicted. ‘ I Ultrasonogram revealed a solid in- traorbital mass in the present case. During orbitotomy it was found that the mass was situated intraconally in the apical region. In three of the seven reported cases the tumors were intraconal. A case of leiomyoma with apical location of the tumor had been described earlier by Nath and Shukla. l 5 Since vascular smooth muscle cells are only found in this region, according to Jakobiec et al. the above finding further adds to the theory of vascular origin of orbital leiomyosarcoma.

The smears revealed tumor cells having elongated nu- clei with blunt ends, which were arranged irregularly or in the form of bundles. Although cytomorphologic fea- tures of orbital leiomyosarcoma have not been described, such cells have been found in FNAC smears of prostatic leiomyosarcoma l6 and we have also noticed similar cyto- morphology in FNAC smears of intestinal leiomyosar- coma and leiomyosarcoma metastasizing to liver.

Histopathologically leiomyosarcoma is characterized by spindle-shaped cells with cigar-shaped nuclei and areas of palisading and intertwining of fascicles. Features such as nuclear pleomorphism, hyperchromatism, giant cells, and increased mitotic activity also characterize leiomyo- sarcoma. Histochemically the cytoplasm stains red with Masson’s trichrome, and ultrastructural features such as cytoplasmic filaments with dense bodies and presence of micropinocytotic vesicles confirm the smooth muscle ori- gin. 9,11-14 Most of these features were present in our case.

The neoplsms which come as differential diagnosis of leiomyosarcoma at microscopic examination include spin-

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Fig. 5. (A) Tumor cell with few cytoplasmic filaments and numerous focal densities. Nucleus showing irregular outline and condensation of chromatin along nuclear membrane ( X 13,200). (B) Magnified view of the plasmalemma showing bundles of filaments on either side and paucity of micropinocytotic vesicles ( x 31,000).

dle-shaped mesenchymal tumors like leiomyoma, fibro- sarcoma, malignant schwannoma, malignant fibrous his- tiocytoma, and rhabdomyosarcoma. According to Jakobiec et a1.,9 the diagnosis of orbital leiomyoma and leiomyosarcoma can be established by the demonstration of nonstriated cytoplasmic filaments with trichrome stain. The red cytoplasmic staining with acid fuchsin in Mas- son's trichrome stain in the present case excludes most of the neoplasms enlisted in differential diagnosis except for leiomyoma and rhabdomyosarcoma. The age of our case corresponds to rhabdomyosarcoma, which is a neoplasm of young age, the average age of onset being 6-7 yr. ' 1 2

However, unlike rhabdomyosarcoma which is a rapidly growing tumor and has a very poor prognosis, our case had a slow and steady course with local recurrences and

total duration of follow-up has been 8% yr now. The absence of cross striations in PTAH stain and by ultras- tructural study also is evidence against rhabdomyosar- coma. Unlike rhabdomyosarcoma, complete exclusion of leiomyoma may appear to be a difficult task in our case. However, a close look at gross, light microscopic, and ultrastructural characteristics dispel that fear. The benign smooth muscle tumors are encapsulated, whereas the lei- omyosarcomas are incompletely encapsulated and invade the orbital fat and musculature. 9,11,14 In the present case although the tumor appeared to be encapsulated, it al- ready had an extension outside the muscle in the medial side and was quite friable leading to incomplete excision. In most of the earlier studies, mitotic figures have been found to be either moderately increa~ed '~ or nume- rous. 9,12 In the present case only 1-2 mitotic figures were seen per 10 high power fields. However, according to Jakobiec et al., even a small number of mitotic figures in a smooth muscle tumor should be alarming. The initial biopsy in the case described by Folberg et al. l4 did not reveal any mitotic figures leading to a false diagnosis of leiomyoma. The case described by Wojno et al. also did not contain large number of mitotic figures. Unlike the benign smooth muscle tumors where reticulin fiber dispo- sition occurs as thick spiraling fibers around the tumor cell fascicles, the reticulin in the present case was irregularly distributed like that of a malignant tumor. The ultrastruc- tural study showed paucity of pinocytotic vesicles, periph- eral location of cytoplasmic filaments, and poorly devel- oped external lamina which are features of leiomyosarcoma. I 7 Morales et al. I s have also found that while the presence of well-developed and abundant struc- tures such as myofilaments, focal densities, dense plaques, and pinocytotic vesicles is no assurance that a tumor is benign, the converse situation-i.e., a paucity or atypia of one or more of these features-is highly likely to be an indicator of malignancy, even in cases where the tumor appears benign by light microscopic examination.

So far the tissue diagnosis of reported cases of leiomyo- sarcoma has been based on histology. Initial diagnosis of our case was also histopathological, but this is possibly the first report to describe the role of FNAC in the diagnosis of recurrence of an extremely rare tumor in a patient who appears to be one of the youngest in the literature.

Acknowledgment The authors thank the regional electron microscope facil- ity at AIIMS, New Delhi. We also thank Mrs. Alice Mathew and Mr. James Luke for their secretarial help in preparation of the manuscript.

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