FROM THE FILES OF THE AFIP
Ossifying
Well-Differentiated Sertolihydig Cell Tumor of the Ovary
Eoghan E. Mooney, MB, MRCPath, Kamini P. Vaidya, MD, and Fattaneh A. Tauassoli, MD A unique case of an ovarian sex cord-stromal tumor occurring in a pregnant 20-year-old is described. The tumor showed central ossification on macroscopic examination. Microscopically, cords and nests of Sertoli cells were identified, mostly away from the abundant central hyalinization, calcification, and ossification. A small number of Leydig cells were present, with isolated Reinke crystals. The presence of these cells could reflect luteinized stromal cells secondary to pregnancy. The Sertoli cells were dominant and the calcified/ossified areas were at the center of a dominant Sertoli nodule. This degree of ossification has never been reported in either ovarian Sertoli tumors or well-differentiated Sertoli-Leydig tumors. Calcifying Sertoli cells neoplasms have been described in the testis, but this case appears to be the first description of a case with similar features in the ovary. Ann Diagn Path01 4: 34-38,200O. Copyright 0 2000 by W.B. Saunders Company Index Words:
Ovary, neoplasm,
calcification,
Case Report
Sertoli-Leydig
cell tumor
Fnnn the Department of cyncmlog and Brtart Pathology, Armed Forces Institute of Pathology, Washington, DC; and the Department of Pathology, St Mary Hapikd, Hoboken, NJ. The opinions nndassntionr contained herein arc the private tis $tht- authors andannot &&~~mtnudarojkialor~ reprcsmting theuitwof~heDepartmt of~Army,Nay,~AirFoneoroftlhcDepa~mmtof~e~e. A&ress corrsz@m&ne to Eoghen E. Mwrq, MB, MRCPath, Depatimtnt of Patho.&, National Ma&kg Hospital, Dublin, Ireland. CopYght 0 2ooO$ WB. Saunders Company 1092-9134/00/~01-00.~l0
sex cords and tubules, some containing round hyaline globules, populated the sclerotic zone (Fig4). The cytologic characteristics of the cells were best seen at the periphery, where closed Sertoli tubules dominated. The nuclei were round to oval with irregular membranes and prominent intracytoplasmic inclusions. Nucleoli were prominent in a small number of cells and were generally inconspicuous. The cytoplasm was vacuolated or clear. h4itotic ligures were rare, with a maximum of l/IO high-power field. Leydig cells with rare Reinke crystals were located in the hypocellular stroma (Fig 5) separating nodular aggregates of Sertoli cell tubules. A minority of cells contained bizarre, multilobated nuclei and rare cells showed hyaline globules. Prominent luteinized cells were seen in the ovarian cortex. The calcifications were located centrally, in the most densely hyalinized portion of the tumor, and consisted of large (up to 7 mm in diameter) amorphous deposits of calcium and most centrally of metaplastic bone (Fig 6). Rarely, adjacent neoplastic tubules contained a laminated calcification, but wellformed psammoma bodies were not a feature of the tumor. The hyalinized stroma contained scattered mast cells and adherent fibrin thrombi were seen in some blood vessels within the tumor. A minority of the neoplastic cells showed punctate positivity for Cam 5.2, and all reacted diffusely with antibody to vimentin. Inhibin was positive in the majority of cells and was ofweak to moderate intensity. Estrogen receptor was negative and progesterone receptor was equivocal (<5% of cells with high background reactivity). Ki-67 reacted with less than 1% of nuclei. p53 was positive in some tumor cells and showed a restricted pattern of distribution, with some Sertoli nodules strongly positive and others negative. Ultrastructurally, the cells contained nuclei with deeply indented nuclear mem-
34
No 1 (February),
A
20-year-old primigravida had a cesarean section for an intrauterine pregnancy at 38 weeks gestation. The pregnancy and delivery were uncomplicated. Intraoperatively, a mass was noted on the left ovary and a partial left oophorectomywas performed. The specimen measured 6.0 X 3.5 X 3.2 cm and weighed 52 g. The cut surface of the tumor showed a solid lesion with a bright yellow peripheral zone and a pale yellow to white central zone (Fig I) that was described as focally calcilied. Tissue processing required decalcification. Microscopically, the tumor was well circumscribed, with a focal pseudocapsule, outside of which a thin rim of ovarian cortical stroma was present. Infiltration of ovarian cortex or blood vessels by tumor cells was not seen, A vague nodular pattern was apparent on scanning magnification. A hyalinized, sclerotic zone separated the peripheral cellular region of the tumor from the central ossified area (Fig 2). At the periphery of the tumor, Sertoli cells were arranged in nests, cords, and simple closed tubules (Fig 3). A paired cell pattern was not readily identifiable. In contrast to the periphery, where little stroma separated the cells, distorted neoplastic
Anna/s
of Diagnostic
Pathology,
Vol4,
2000:
pp 34-38
Ovarian
Ossifying
Sertoli-Leydig
Tumor
Figure 1. The cut surface of the tumor appeared well delineated, with a mottled yellow appearance to the distinct peripheral band formed by the more cellular region. In contrast, the central area of hyalinization, calcification, and ossification appeared white. branes and single nucleoli. Unlike previous studies,’ t!vo cell types (light and dark) wcrc not identified. The ccl1 membranes were smooth and formed intermediate junctions. Early microvilli were present focally as were small lumina. The q-toplasm contained smooth and rough endoplasmic reticulum, the latter assuming a whorlcd configuration in places. Mitochondria and lipid clroplcts were prominent. Charcot-Biittcher
filaments, Spangaro plexes were not seen.
Figure 2. The cellular peripheral central ossified region by a sclerotic, lin-eosin stain; magnification X35.)
Figure 3. The peripheral Sertoli tubules surrounded magnification X 175.)
zone is separated from the hyalinized zone. (Hematoxy-
filaments,
or
ribosome-lamellae
com-
Discussion Well-differentiated
toli
cell tumors
Sertoli-Leydig cell and pure Serof the ovary may have a range of
region was composed by a distinct reticulin layer.
of closed (Reticulin;
36
Mooney,
Vaidya,
and Tavassoli
hamartomas are usually composed of uniform tubules with a prominent paired-cell arrangement and, rarely, calcification.3 A karyotype was not performed in the patient in our case, but a successful pregnancy excluded androgen insensitivity syndrome. Sertoli cell tumors may occasionally produce either hyperestrinism or virilization.’ While the former may be difficult to detect in premenopausal women, our patient had no evidence of virilization. A variety of ovarian tumors may contain calcific deposits. In some, these are incidental microscopic findings that reflect a dystrophic process and are variable in frequency. In others, they are of sufficient frequency to be regarded as a diagnostic feature of the tumor. Possibly the most common are the psammoma bodies of serous neoplasms. When these are extensive (>75% of the epithelial nests) and the tumor lacks high-grade nuclei, the term psanzmocarcinoma has been used.’ Rarely, osseous metaplasia has been identified in serous cystadenocarcinoma5 and calcilication is identilied relatively frequently in the wall of mutinous cystadenomas. The eosinophilic material found in the acini of carcinoid tumors may undergo calcification” and terato-
Figure 4. In the sclerotic zone, the Sertoli tubules often contained round hyalin globules (arrows). (Hematoxylin-eosin stain; X290.)
appearances. Cysts are found in larger tumors and those in younger patients. Necrosis may be a feature of neoplasms greater than 10 cm in diameter.’ The yellow color is also characteristic of these tumors and reflects the presence of intracytoplasmic lipid. The case reported here differs from previously reported examples of welldifferentiated ovarian Sertoli-Leydig cell or pure Sertoli tumor in its distinct pattern of hyalinization, the presence of central calcification, and ossification. Hyalinization may occur in Sertoli tumors, but usually appears as sclerosis of a tumor nodule, with frequent preservation of the ghost outline of tubules. Localized areas of fibrosis may compress and distort sex cord tubules. Extensive hyalinization was reported in one of 10 cases in one study,2 but the diffuse sclerosing process with associated calcification and osseous metaplasia, as seen in the current case, has not been reported in cases that were not unusual variants (see below). Microscopic foci of calcification in hyaline bodies were noted in five of 28 Sertoli cell tumors by Tavassoli and Norris.’ Lesions arising in the background of androgen insensitivity syndrome were specifically excluded from the larger of these two series’; such adenomas or
Figure “Leydig” tubules.
5.
Rare Leydig cells contained Reinke crystals. The cells were generally in between nodules of Sertoli (Hematoxylin-eosin stain; magnification x600.)
Ovarian
Ossifying
Sertoli-Leydig
Tumor
Figure 6. (Left) Dense areas of calcification were evident in the sclerotic areas. (Right) Ossification was dominant central zone of the tumor. Nests of stroma cells with a signet ring cell appearance were evident in some of the lacunar adjacent to the bony trabeculae. (Hematoxylin-eosin stain. Magnifications: left, x215; right, x300.)
mas may contain bone or cementurn. Foci of calcification may be detected in the hyaline plaques of fibrothecomas7 and juvenile granulosa cell tumors may show calcification in addition to hemorrhage and necrosis.‘j Rare Sertoli-Leydig cell tumors have been reported with bone as a mesenchymal heterologous element.8a9 Sertoli cell tumors with complex tubules’ and associated with Peutz-Jeghers syndrome are generally multiple and calcified.‘0 Both hyalinization and calcification may be extensive, resulting in obliteration of the cellular component of these tumors. Deposits of calcium are found in 80% ofgonadoblastomas and a laminated pattern resembling the metaplastic bone seen in the current case has been illustrated.3 Calcification in nonneoplastic settings may be seen as microscopic deposits in surface epithelial inclusions, in the walls of endometriotic cysts, or, rarely, as an idiopathic process.” In the testis, a distinctive variant called large cell calcifying Sertoli cell tumor has been described.‘2-‘5 This is a neoplasm that usually behaves in a benign fashion and that may be associated with a range of complex dysplastic syndromes, such as Carney’s complex and Peutz-Jeghers syndrome.‘j However, the current case
in the most spaces and
does not appear to be a female counterpart of large cell calcifying Sertoli cell tumor of the testis. The cells resemble the sex cord pattern of differentiation termed Sertoli cells in the ovary, and lack the abundant eosinophilic cytoplasm of large cell calcifying Sertoli cell tumor. Clinical examination of our patient did not reveal features of Peutz-Jeghers syndrome, nor was there a family history of any features of the syndrome. Another entity reported in the testis, sclerosing Sertoli cell tumor, differs from the current case by the absence of calcification and a more uniform pattern of sclerosis.16
Acknowledgment The authors photography.
thank
Robin-Anne
V. Ferris
for assistance
with
References I. Tavassoli FA, Norris HJ: Sertoli cell tumors of the ovary. A clinicopathologic study of 28 cases with ultrastructural observations. Cancer 1980;46:2281-2297 2. Young FM, Scully RE: Ovarian Sertoli cell tumors: A report of 10 cases. Int J Gynecol Pathol 1984;2:349-363 3. Scully FE, Young RH, Clement PB: Tumor of the ovary,
38
Mooney,
Vaidya,
maldeveloped gonads, fallopian tube and broad ligament, in RosaiJR, Sobin LH (eds): Atlas of Tumor Pathology. Fascicle 23, series 3. Washington, DC, Armed Forces Institute of Pathology, 1998, p399408 4. Gilks CB, Bell DA, Scully RE: Serous psammocarcinoma of the ovaiyand peritoneum. IntJ Gynecol Pathol 1990;9:110-I21 5. Barua R, Cox LW: Occurrence of bone in serous cystadenocarcinomaof the ovarye Aust NZJ Obstet Gynecol 1982;22:183-186 6. Young RH, Scully RR: Sex cord-stromal, steroid cell, and other ovarian tumors with endocrine, paraendccrine and paraneoplastic manifestations, in Kurman RJ (ed): Blausteins’s Pathology of the Female Genital Tract (ed 4). New York, NY, Springer-Verlag, 1994, pp 783-848 7. Young RH, Clement PB, Scully RR: Calcilied thecomas in young women: A report of four cases. Int J Gynecol Pathol 1988;7:343-350 8. Roth LM, Anderson MC, Govan ADT, et al: Sertoli-Lqdig cell tumors: A clinicopathologic study of 34 cases. Cancer I98 I ;48: 187- 197 9. Tragerman JL: Arrhenoblastoma of the ovary. Arch Pathol 1935;19:907-908
and Tavassoli IO. Scully RE: Sex cord tumor with annular tubules. A distinctive ovarian tumor of the Peutz-Jeghers syndrome. Cancer 1970;25:1107II21 1 I: Clement PB, Cooney TP: Idiopathic multifocal calcilication of the ovarian stroma. Arch Pathol Lab Med 1992; Il6:204-205 12. Proppe KH, Scully RR: Large-cell calcifying Sertoli cell tumor of the testis. Am J Clin Pathol 1980;74:607-619 13. Proppe KH, Dickersin GR: Large-cell calcifying Sertoli cell tumor of the testis: Light microscopic and ultrastructural study. Hum Pathol 1982;13:1 109-l I I4 14. Perez-Atadye AR, Nunez AE, Carroll WL, et al: Largecell calcifying Sertoli cell tumor of the testis. Cancer 1983;51:22872292 15. Plats C, Algaba F, Andujar M, et al: Largecell calcifying Sertoli cell tumor of the testis. Histopathology 1994;26:255-259 16. Zukerberg LR, Young RH, Scully RR Sclerosing Sertoli cell tumorofthe testis.Areport oflOcases.AmJSurgPathol 1991;15:829834