Clear Cell Struma Ovarii Robert H.Young Professor of Pathology Director of Anatomic Pathology Massachusetts General Hospital Harvard Medical School Boston, Massachusetts, U.S.A.

Clinical History: A 39-year-old woman was found to have an 8 cm solid tan-white, focally cystic right ovarian mass. The neoplasm was confined to the ovary. Figure 1 Click to view with ImageScope Click to view with a Web-Based Viewer Diagnosis: Clear cell struma ovarii Discussion: Struma ovarii, the most common monodermal teratoma, refers to a tumor in which thyroid tissue is the predominant or sole component or forms a grossly recognizable component of a more complex teratoma. Although meticulous examination of dermoid cysts has revealed thyroid tissue in 20% of the cases, this component is recognized grossly in considerably less than 5% of the cases. The peak frequency is in the fifth decade, although occasional cases have been reported in prepubertal and postmenopausal females. This case is used to bring up unusual microscopic features of struma recently highlighted [1]. It also exemplifies well the diverse problems the many patterns and cell types of ovarian tumors may cause [2]. Aside from the usual manifestations relating to the presence of a mass, struma may be associated with a number of unusual clinical manifestations. Ascites occurs in approximately one-third of the cases, and occasionally Meigs' syndrome (ascites and hydrothorax associated with a benign ovarian tumor) is present [3]. Although many, if not most, strumas probably produce thyroid hormones at subclinical levels, clinical evidence of hormone production by these tumors occurs in only about 5% of cases. Struma is usually recognizable as brown or greenish-brown, predominantly solid, gelatinous tissue, usually in pure form and less often associated with a dermoid cyst or mixed with a solid carcinoid tumor as a strumal carcinoid. Rarely struma is found within the wall of a mucinous or serous cystadenoma or is admixed with a Brenner tumor. Some strumas appear as unilocular or multilocular cysts containing brown to green, mucked or gelatinous fluid [4]. Occasionally, the opposite ovary contains a dermoid cyst, and rarely, another struma. Struma may resemble normal thyroid tissue or a thyroid adenoma, with patterns including macromolecular, microfollicular, sheetlike (embryonal), solid tubular, or trabecular, alone or in combination. Cystic strumas may have only scant recognizable thyroid tissue that is easily overlooked, especially if the pathologist is unaware that strumas can be predominantly or entirely cystic. As in the seminar case, clear cells may be present and occasionally the tumor has prominent oxyphilic cells. Colloid within the follicles often contains birefringent calcium oxalate crystals. The colloid and cytoplasm of the tumor cells are typically immunoreactive for thyroglobulin. Uniformly accepted criteria for malignant change in struma have not been established [5, 6]. As in the thyroid gland, a papillary pattern with typical nuclear characteristics of papillary thyroid carcinoma, or similar nuclear features in tumors with a follicular pattern, provide microscopic evidence of carcinoma. Tumors with these features, however, are often clinically benign. On gross examination, cystic strumas can be mistaken for mucinous cystic tumors; the green to brown color of the former helps in the differential diagnosis. The wide variety of microscopic patterns that can be encountered in struma ovarii can result in diagnostic confusion with ovarian tumors of diverse types. Oxyphilic strumas with solid or tubular patterns may be mistaken for other oxyphil cell tumors, such as steroid cell tumors or Sertoli cell tumors, respectively. Similarly, clear cell strumas may be misdiagnosed as clear cell carcinoma. Tumors with a microfollicular and trabecular pattern may be misdiagnosed as a granulosa cell tumor. Conversely, clear cell carcinomas, endometrioid carcinomas, SLCTs, pregnancy luteomas, and a variety of other ovarian tumors may contain follicle-like spaces filled with material resembling thyroid colloid, but other features of such tumors almost always permit their identification. In problematic cases, an association with a dermoid cyst or teratomatous elements of another type, the demonstration of foci of typical thyroid follicles, the presence in the colloid of birefringent calcium oxalate crystals, and immunoreactivity for thyroglobulin may be helpful in confirming the thyroid nature of the tumor. Occasionally a struma is admixed with mucinous neoplasia or contains luminal mucin, as might be expected in a mixed endodermal teratoma. Finally, exceptional cases of follicular carcinoma of the thyroid gland have metastasized to the ovary, a differential diagnosis facilitated by knowledge of the primary tumor, the typical patterns of a metastatic tumor in the ovary, and the absence of an associated dermoid cyst [7]. Although 5 to 10% of strumas have been considered malignant, less than half of such tumors have been associated with extraovarian spread to sites including the peritoneum, the contralateral ovary, regional lymph nodes, bone, liver, brain, lungs, and mediastinum. In the remaining cases, the diagnosis has been made on microscopic criteria alone, and many such cases are now known to be strumal carcinoids. Devaney and colleagues [6] found that most cases of struma with atypical or malignant features on microscopic examination are not associated with a clinically malignant course. These investigators studied 54 cases of struma which were subdivided into "proliferative" struma (41 cases) and "malignant" struma (13 cases). The former group were composed of densely packed follicles or papillary formations, but lacked the distinctive nuclear features of papillary carcinoma, vascular invasion, and mitotic activity. After a mean follow-up interval of 8.7 years, all the patients were clinically free of disease. Eleven of the 13 malignant strumas were papillary carcinomas of thyroid type, whereas two resembled follicular carcinoma with "capsular" and vascular invasion. One of the patients with papillary carcinoma had peritoneal involvement by similar tumor at the time of oophorectomy; the peritoneal lesions were incompletely resected. None of the patients received adjuvant therapy. On follow-up examination (mean follow-up interval 7.3 years), none of the patients had clinical evidence of recurrent disease, including the patient with Stage III disease at presentation. References Szyfelbein WM, Young RH, Scully RE. Struma ovarii simulating ovarian tumors of other types: A report of 30 cases. Am J Surg Pathol 1995; 19:21-9. Young RH, Scully RE. Differential diagnosis of ovarian tumors based primarily on their patterns and cell types. Semin Diagn Pathol 18:161-235, 2001. Kempers RD, Dockerty MB, Hoffman DL, Bartholomew LG. Struma ovarii - ascitic, Kragel PJ, Devaney K, Merino MJ. Struma ovarii with peritoneal implants: A case report with lectin histochemistry. Surg Pathol 1991;4:274-281. Szyfelbein WM, Young RH, Scully RE. Cystic struma ovarii: A frequently unrecognized tumor. A report of 20 cases. Am J Surg Pathol 1994;18:785-788. Hasleton PS, Kelehan P, Whittaker JS, Burslem RW, Turner L. Benign and malignant struma ovarii. Arch Pathol Lab Med 1978;102:180-184. Devaney K, Snyder R, Norris HJ, Tavassoli FA. Prolferative struma ovarii and histologically malignant struma ovarii - a clinicopathologic study of 54 cases. Int J Gynecol Pathol 1993;12:333-343. Young RH, Jackson A, Wells M. Ovarian metastasis from thyroid carcinoma twelve years after partial thyroidectomy mimicking struma ovarii. Int J Gynecol Pathol 1994;13:181-185.