Monodermal teratomas

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PATHOLOGY Mini-symposium: germ cell tumours of the ovary (part III)

M o n o d e r m a l teratomas

P. B. Clement and R. H. Y o u n g

STRUMA OVARII Clinical features Although as many as 20% of dermoid cysts contain thyroid tissue on microscopic examination, the term 'struma ovarii' is reserved for the much less common situation in which thyroid tissue is the predominant, or sole component, or forms a grossly recognizable component of a teratoma. The peak frequency is in the fifth decade, but occasional cases occur in prepubertal and post-menopausal females. Aside from the usual clinical presentation related to a mass, struma may be associated with other less common clinical manifestations. Ascites occurs in approximately one-third of the cases, occasionally accompanied by Meigs' syndromeJ Although many strumas probably produce thyroid hormones at subclinical levels, clinical evidence of hormone production by these tumours is rare. 2,3 The size of the struma may be one factor that determines the frequency of hyperthyroidism; in one study, hyperthyroidism was rare in cases of struma in which the tumour was < 3 cm in diameter. 1 In some patients with clinical or laboratory evidence of hyperthyroidism, hyperfunctioning struma ovarii has been diagnosed by the finding of high 131I uptake in the pelvis, with low uptake in the neck. In other cases, struma-associated hyperthyroidism has not been recognized until the symptoms regressed after removal of an ovarian tumour; in some of these patients, a prior thyroidectomy had no effect on the hyperthyroidism.

Pathological features Struma is usually brown or greenish-brown, predominantly solid, gelatinous tissue which may be pure, Philip B. Clement, MD, Vancouver Hospital and Health Sciences Centre and the University of British Columbia, Department of Pathology and Laboratory Medicine (Anatomical Pathology), Vancouver, British Columbia. Robert H. Young, MD, the James Homer Wright Pathology Laboratories of the Massachusetts General Hospital and the Department of Pathology, Harvard Medical School, Boston, USA Current Diagnostic'Pathology (1995)2, 214 221 9 1995P...... Prol~ssionalLtd

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Fig. 1--Cystic struma ovarii.

associated with a dermoid cyst, or mixed with a carcinoid turnout as a strumal carcinoid (see Carcinoid Tumours). Some strumas are unilocular or multilocular cysts with mucoid or gelatinous contents; a green to brown colour of the cyst contents is, again, an important clue to the correct diagnosis (Fig. 1). 4 We suspect that some of the strumas reported in association with a cystadenoma in the older literature 5 may be due to misinterpretation of the cystic component of a struma as a surface epithelial tumour. 4 The struma is usually easily recognizable on microscopic examination, but unusual patterns mimicking those of a thyroid adenoma, including microfollicular, pseudotubular, trabecular, or solid nests or sheets, alone or in combination, may create diagnostic problems (Fig. 2). 6 Birefringent calcium oxalate crystals in the colloid may be a helpful clue to the correct diagnosis in some cases. The neoplastic cells typically have bland or mildly atypical nuclei and mitotic figures are rare in the great majority of cases; as many as 5 mitotic figures per 10 high-power-fields, however, have been encountered in rare cases. 6 As in thyroid neoplasms, oxyphil cells (Fig. 2) or clear cells may occasionally be the predominant cell type. 6 In cystic strumas, the cysts are often lined by indifferent flat to cuboidal epithelial cells, and

MONODERMALTERATOMAS 215

Fig. 2--Cellular struma ovarii composed of oxyphilic cells arranged in nests and trabeculae. Several thyroid-type follicles are visible at extreme left. H&E.

Fig. 3--Cystic struma ovarii, Note flattened cells with a nonspecific appearance lining the cyst (top of figure). A few thyroid type follicles are present within the cyst wall. H&E. typical thyroid follicles may be only sparsely and irregularly lbund within the fibrous septa (Fig. 3)) Rare findings include an associated mucinous tumour or luminal mucin (suggesting a mixed endodermal teratoma) and foci of 'thyroiditis'. hnmunoreactivity of the cell cytoplasm and colloid l~r thyroglobulin can establish the diagnosis of struma, especially in cases with unusual patterns or cell types. Although unitbrmly accepted microscopic criteria for malignant struma have not been established, a papillary pattern with typical nuclear characteristics of papillary thyroid carcinoma, or similar nuclear features in tumours with a follicular pattern, provide microscopic evidence of carcinoma. Tumours with these features, however, are often clinically benign (see Prognosis).

Differential diagnosis Cystic strumas can be distinguished from cystic epithelial tumours based on the green to brown colour of the former, and on microscopic examination, the focal presence of thyroid follicles in the septa, the presence of typical struma in some cases, and the occasional association with a dermoid cyst. 50xyphil and clear cell strumas with insular, solid or pseudotubular patterns and rare thyroid

follicles may be mistaken for steroid cell tumours, Sertoli cell tumours, paragangliomas, primary or metastatic clear cell carcinomas, hepatoid carcinoma, metastatic hepatocellular carcinoma, and metastatic malignant melanoma. 6 A prominent microfollicular pattern has occasionally caused confusion with the Call-Exner bodies of a granulosa cell tumour. 6 In these and other problematic cases, an association with a dermoid cyst, the presence of typical thyroid follicles, the presence of birefringent calcium oxalate crystals, and immunoreactivity for thyroglobulin facilitate the diagnosis. A struma of unusual type in a dermoid cyst may suggest the diagnosis of carcinoid tumour, hepatoid yolk sac tumour, or malignant melanoma. The distinctive nuclear features of the carcinoid tumour and the malignant nuclear features and typically brisk mitotic activity of melanomas and yolk sac tumours militate against a diagnosis of struma. Additional distinguishing features include the frequent immunoreactivity of carcinoid tumours for neuroendocrine markers, the presence of pigment and immunoreactivity for S-100 protein and HMB-45 in melanomas, and the presence of hyaline globules and immunoreactivity for alpha-fetoprotein in hepatoid yolk sac tumours. It should be remembered that ovarian tumours of diverse types may exhibit struma-like patterns. Clear cell carcinomas, endometrioid carcinomas, Sertoli-Leydig cell tumours, and pregnancy luteomas may contain folliclelike spaces filled with material resembling thyroid colloid, but other features of such tumours and an absence of immunoreactivity fl)r thyroglobulin almost always permit their identification. A final rare consideration in the differential diagnosis of struma is metastatic follicular carcinoma from the thyroid gland] This differential diagnosis is facilitated by knowledge of the primary mmour, lhe typical patterns of a melastafic tumour in the ovary, and the absence of an associated dermoid cyst.

Prognosis Although 5-10% of strumas have been considered malignant in the past, less than half of such tumours have been associated with extraovarian spread. In the remaining cases, the diagnosis has been made on microscopic criteria alone, and many such cases are now known to be strumal carcinoids (see below). Devaney and colleagues have recently found that, with rare exceptions, cases of struma with atypical or malignant features on microscopic examination have a clinically benign course on follow-up. 8 Preliminary data from another study of 34 cases of malignant struma with 20-year follow-up data are available. 9 Criteria for inclusion in the study were microscopic evidence of papillary or follicular carcinoma by the criteria described above, clinical evidence of malignant behaviour, or both. On follow-up examination, local or distant spread of tumour occurred in 16 patients. Factors that were predictive of recurrence included tumour size, the presence of adhesions or ascites, and a solid microscopic architecture. Features that were not useful in predicting behaviour

216 CURRENTDIAGNOSTICPATHOLOGY included mitotic activity, the presence of an infiltrative border, and the presence of vascular invasion. This study indicates the need for prolonged follow-up examination is assessing the frequency of malignancy of struma ovarii, as some of the tumours recurred late, up to 27 years postoperatively. Another observation from this and other studies 1~ is that occasional cases of struma associated with extraovarian spread may have a histologically benign appearance, as can the extraovarian tumour. The term 'strumosis' has been applied to benign appearing peritoneal implants in such cases, l~ Struma ovarii with extraovarian spread may be associated with an indolent clinical course; the metastases may appear many years after oophorectomy and the survival is often prolonged. The survival rates at 5, 10, and 25 years in the study cited above were 92%, 85%, and 79%, respectively. 9 CARCINOID TUMOURS Although ovarian carcinoid tumours are occasionally encountered in an apparently pure form, approximately 90% of them are associated with other teratomatous components, typically a dermoid cyst, or less commonly, struma (strumal carcinoid), a mature solid teratoma, a cystic mutinous turnout, or a microscopic focus of teratoma. Carcinoid tumours of germ cell origin are of four types, which have sufficiently distinctive clinicopathologic features to warrant their separate classification: insular, trabecular, strumal, and mucinous. Insular carcinoid This, the most common type of primary ovarian carcinoid turnout, occurs in patients in their fourth to eighth decades who usually present with the manifestations of a slowly growing ovarian tumour. Approximately onethird of the patients have had pre-operative clinical evidence of the carcinoid syndrome that disappears after oophorectomy; rarely the syndrome is the presenting manfestation of the tumour. 12 The syndrome typically occurs in the absence of extraovarian spread because the ovarian venous drainage bypasses the liver, which inactivates the hormones responsible for the syndrome. The patients with the syndrome are almost always > 50 years of age and have tumours larger (usually > 7 cm in maximal dimension) than those without the syndrome. Insular carcinoid tumours are almost always confined to the ovary at the time of laparotomy. Occasional patients, both with and without the syndrome, have had ascites. 12 The tumour may form a small nodule that protrudes into the lumen or thickens the wall of a dermoid cyst or, rarely, a cystic mucinous tumour; 13 it may lie within a mature solid teratoma or form a large homogenous mass that replaces the ovary. The neoplastic tissue is predominantly solid, firm, tan to yellow, and variably fibrous. Cysts filled with clear fluid are occasionally present, and rarely the tumour is predominantly cystic. All the tumours have been unilateral. On microscopic examination, discrete cellular nests are separated by a scanty to abundant fibromatous stroma;

the appearance resembles that of midgut carcinoids. 12 The tumour cells have round, uniform nuclei containing coarse chromatin and absent to rare mitotic figures. The peripheral cells of the islands typically have abundant cytoplasm that often contains prominent red, orange, or brown argentaffin granules. Small round acini lined by columnar cells often containing argentaffin granules commonly puncture the cellular islands, particularly at their periphery. An eosinophilic secretion, which may undergo psammomatous calcification, is typically present within the acini. The tumour may merge with respiratory or gastrointestinal epithelium, whereas in others, the neoplastic tissue is intimately admixed with or abuts a mucinous cystic tumour. Neuron-specific enolase 14 and serotonin 15 have been demonstrated immunohistochemically within the tumour cells. In less than 10% of the cases, the neoplastic cells are immunoreactive for one or more neurohormonal peptides (see Trabecular Carcinoids). 16 Pleomorphic, reniform or dumbbell-shaped dense core granules are present on ultrastructural examination. 12 In the absence of teratomatous elements, the tumour cannot always be distinguished from a metastatic insular carcinoid, which is usually of ileal origin. Evidence favouring or establishing the diagnosis of metastasis includes the presence of a definite or probable intestinal carcinoid tumour, bilateral involvement, intraovarian growth as multiple nodules, extraovarian metastases particularly to mesenteric lymph nodes and liver, and postoperative clinical or laboratory evidence of the carcinoid syndrome. The primary tumour that is most often confused with the insular carcinoid tumour is the microfollicular granulosa cell tumour. The Call-Exner body, which is characteristic of the latter, however, differs from the carcinoid acinus by having irregular margins and containing watery eosinophilic fluid and occasional shrunken nuclei in its lumen. The granulosa cells usually have scanty cytoplasm, and their nuclei, which are angular and haphazardly oriented to one another, are pale and often grooved. Sertoli-Leydig cell tumours may have tubules that simulate the acini of insular carcinoids and their heterologous forms may rarely contain carcinoid tumourlets as a prominent component. Other features of the Sertoli-Leydig cell turnout, however, almost always permit a correct diagnosis. Occasionally, a carcinoid tumour has been mistaken for adenocarcinoma, a benign or malignant adenofibroma, or a Brenner tumour, particularly when the fibromatous component of the tumour is abundant, but careful examination of the epithelial elements of these tumours enables one to identify them. In any case, the demonstration of argentaffin or argyrophil granules in a characteristic distribution is strong evidence for a carcinoid tumour. Immunostaining for chromogranin, serotonin, or a wide variety of peptide hormones or the electronmicroscopic demonstration of dense core granules may be helpful in difficult cases. Most of the manifestations of the carcinoid syndrome disappear after oophorectomy, although tricuspid insufficiency has persisted or progressed postoperatively in several patients in the absence of persistent or recurrent

MONODERMALTERATOMAS 217 tumour. 12,17 Rare patients have died of intra-abdominal recurrent tumour, 12,~8and two patients with the carcinoid syndrome in whom the tumour was first visualized at autopsy had ascites and a thick, pearly-white fibrous coating of the visceral and parietal peritoneal surfaces. 19'2~ Trabecular carcinoid This subtype of carcinoid is only about one-third as common as insular carcinoids. Almost all the affected women are in their third to sixth decades. 21,22 The presenting manifestations are typically related to the presence of a slowly growing neoplasm in the absence of the carcinoid syndrome. Rare patients have had severe chronic constipation relieved by oophorectomy (see below). 2x24 No patients have died from spread of tumour, although a peritoneal implant was discovered in one case 2 years after oophorectomy. 2~ The gross appearances are similar to those of insular carcinoid, with teratomatous elements present in almost all the cases; all the tumours have been unilateral. These tumours are characterized by long, wavy, parallel ribbons of cells separated by a scanty to abundant fibromatous stroma, creating an appearance similar to that of foregut and hindgut carcinoids. The ribbons are composed of columnar cells, usually one or two cells thick, with oblong nuclei oriented perpendicular to the axis of the ribbons. The moderately abundant eosinophilic cytoplasm typically contains argyrophilic granules, and much less commonly, argentaffin granules. The nuclei contain finely dispersed chromatin and occasional mitotic figures. An insular pattern is observed as a minor feature in about 20% of the cases. One or more neurohormonal polypeptides have been demonstrated in approximately half the cases, including somatostatin, glucagon, pancreatic polypeptide, vasoactive intestinal polypeptide, neurotensin, enkaphalin, catcitonin, and ACTH. x{'Peptide YY, which has an inhibitory effect on intestinal motility, has been found in three cases, including two patients with chronic constipation relieved by oophorectomy. >,> In contrast to insular carcinoids, the dense core granules are small, round, and uniform. 21,25 Primary trabecular carcinoid is distinguished from metastatic trabecular carcinoid by the same criteria as those used for distinguishing metastatic from primary insular carcinoids. A strumal carcinoid can be excluded only by extensive sampling to rule out thyroid tissue associated with the carcinoid trabeculae. In an occasional case, the ribbons of a trabecular carcinoid can be confused with unusually long sex cord formations of a Sertoli-Leydig cell tumour, but other features of the latter almost always allow one to make the distinction. Argyrophilia or argentaffinity of the cytoplasm is also helpful in confirming the diagnosis of carcinoid in these cases.

patients have ranged from 20 to 78 years of age. Only one patient has had the carcinoid syndrome, but in almost 10% of them, there have been manifestations suggesting function of the thyroid component. 26 Three patients have had chronic constipation relieved by removal of the tumour. 23 In the only case with documented extraovarian spread at presentation, the metastatic tumour consisted only of benign-appearing thyroid tissue, and the patient was alive with tumour 1 year after presentation. 29 One other patient with a clinically malignant strumal carcinoid died from the tumour 2.5 years postoperatively .26 Strumal carcinoids may be pure or associated with a teratoma. In the latter situation, the tumour may form a solid nodule that protrudes into the cavity of a d ermoid cyst or thickens its wall; less commonly, it is the predominant constituent of a mature, solid teratoma or is a microscopic focus within a mature teratoma. The strumal carcinoid may have a homogeneous yellow or tan sectioned surface that is usually solid or predominently solid, but occasionally predominantly cystic, in some cases the strumal and carcinoid components are each grossly recognizable. The two components, either of which may predominate, are usually intimately admixed (Fig. 4), but are occasionally only contiguous. The carcinoid component is almost always trabecular (Fig. 4) or mixed trabecularinsular pattern with the former predominating, and the strumal component resembles pure struma ovarii. In areas where the two components are admixed, carcinoid cells may replace the original epithelial lining of colloid-filled spaces. Small foci of glands or cysts lined by mucinous epithelium are present in up to half the cases, and occasional tumours have contained a component of mucinous carcinoid. 2(~'3~Rare strumal carcinoids have had amyloid in their stroma) ~ The neoplastic cells, particularly within the carcinoid component, are variably immunoreactive for neuronspecific enolase, chromogranin, synaptophysin, serotonin, and enigmatically, as in some intestinal carcinoid tumours, prostatic acid phosphatase. H27,2s,32,33 In 42% of the cases in one series] 6 the neoplastic cells were immunoreactive for one or more of the neurohormonal

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Strumal carcinoid These tumours have been reported with a frequency similar to that of the insular carcinoid tumour. 26 2s The

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Fig. 4 ~ S t r u m a l carcinoid. In this field, only a few small t h y r o i d - t y p e follicles are apparent (center and top right).

218

CURRENT DIAGNOSTIC PATHOLOGY

peptides noted above (see Trabecular Carcinoid). In another series, 28 all five tumours were positive for one or more peptide hormones, including somatostatin, glucagon, insulin, gastrin, and calcitonin. In contrast to medullary carcinoma of the thyroid, the last hormone has been found in only rare strumal carcinoids. Peptide YY was found in the carcinoid component in the three patients cited above with chronic constipation. 23 Both the strumal component and occasionally foci within the carcinoid component are immunoreactive for thyroglobulin. Ultrastructural examination reveals uniform, round granules within the trabecular cells; the follicles are lined by similar neuroendocrine-type cells, thyroid epithelial-type cells, or a mixture of the two. 27,28 Ultrastructural evidence of both thyroidal and carcinoid differentiation in the same cell may be seen. 32 The pattern of the strumal carcinoid is so distinctive that it is usually easy to distinguish from other neoplasms. Occasional strumal carcinoids with a minor component of thyroid tissue (Fig. 4) may be misdiagnosed as pure trabecular carcinoids. Because the latter are considerably less common than strumal carcinoids, they should be thoroughly sampled to exclude a strumal component. In the older literature, strumal carcinoid was most frequently mislabelled malignant struma even though it does not resemble any of the forms of carcinoma encountered in the thyroid gland, including medullary carcinoma.

Fig. 5--Mucinous carcinoid. In addition to the goblet cells, note several cells containing subnuclear reddish (argentaffin) granules (H&E).

Mucinous carcinoid

Primary mucinous carcinoids of the ovary are rare and our knowledge of them is incomplete. Only two cases have been reported in detail, 34,35 although a number of unpublished cases are currently being studied (Talerman et al, in preparation). The age of the patients and the clinical presentation are similar to those of patients with other types of ovarian carcinoid tumours. At the time of laparotomy, however, some patients have evidence of extraovarian spread. 34,35 The tumours resemble other ovarian carcinoid turnouts on gross examination. They occur in pure form or are associated with a mature teratoma or an epidermoid cyst. The characteristic microscopic appearance is that of small glands with small to inapparent lumens or nests scattered through a scanty to abundant fibromatous stroma (Fig. 5). The acini and nests are composed of varying numbers of goblet cells and argyrophil cells, some of which may also be argentaffinic. The nuclei are uniform, small, and round to oval. Small pools of mucin may lie within cystically dilated glands or within the stroma (Fig. 5). In some cases, there is an invasive poorly differentiated component in the form of a signet-ring adenocarcinoma, potentially mimicking a Krukenberg tumour. As noted above, occasional mixed mucinousstrumal carcinoids have been reported. 3~ The tumours may be immunoreactive for chromogranin (Fig. 6), CEA, pancreatic polypeptide, serotonin, and gastrin. 34,35 Dense core granules have been identified on ultrastructural examination in one of the reported cases. 34 Mucinous carcinoid tumours metastatic from the

Fig. 6--Mucinous carcinoid (Chromogranin stain).

appendix or elsewhere are differentiated from the primary form on the basis of operative and pathologic criteria similar to those used for distinguishing metastatic from primary insular carcinoids. Most of the same criteria facilitate the distinction of a primary mucinous carcinoid with a signet-ring adenocarcinomatous component from a Krukenberg tumour. Mucinous tumours of the ovary, unlike mucinous carcinoid tumours, are typically predominantly cystic on gross examination and are composed of large glands or cysts lined by mncinous epithelium. The latter, however, frequently contains argyrophil and argentaffin cells, although they tend to be less numerous than in mucinous carcinoid tumours. Although only a small number of cases have been studied, the risk of extraovarian spread is probably greater in cases of nmcinous carcinoid tumour than in cases of other primary ovarian carcinoids (Talerman et al, in preparation). The usual staging procedures therefore should be performed if the diagnosis is suspected or confirmed by intra-operative frozen section examination. In one of the reported cases, which contained a signetring adenocarcinomatous component within the primary tumour, metastatic signet-ring carcinoma was present in the contralateral ovary and in the pelvic lymph nodes at the initial laparotomy. 34 The appendix should also be

MONODERMAL TERATOMAS

219

removed for thorough pathological examination. On the basis of preliminary data (Talerman et al, in preparation), the most important prognostic factor is stage. Tumours that are stage I have a good prognosis, whereas those with extraovarian spread are usually associated with disease progression and death from tumour. The patient with metastatic signet-ring adenocarcinoma at the time of laparotomy noted above died from the tumour 1 year after diagnosis. 34 Rare ovarian earcinoid tumours

Rare ovarian carcinoids include those of spindle cell type resembling their pulmonary counterparts and those with non-specific, sometimes poorly differentiated patterns. 36 These tumours may merge morphologically with ovarian small cell carcinomas of pulmonary type. N E U R O E C T O D E R M A L TUMOURS

These rare tumours closely resemble neoplasms of the central nervous system (CNS). The 25 cases in the only large series 37 were subdivided into three categories: (1) differentiated (ependymomas) (6 cases), (2) primitive (12 cases), (3) anaplastic (7 cases). Four other ovarian ependymomas also have been described. 3s~l The patients in the aforementioned series ranged in age from 6 to 69 years; there was a trend for increasing mean age among the three major subgroups: (1) anaplastic (16 years), (2) primitive (23 years), (3) differentiated (30 years). The presenting symptoms were usually those of a pelvic mass; at laparotomy, 14 of the 25 patients had extraovarian spread, usually in the tk)rm of peritoneal implants. The tumours vary from cystic to solid, and from 4 to 20 c m ( n l c a n , 14 cm) in diameter. ;~v lntracystic or surface papillary excrescences are present in some cases. The neoplastic tissue is typically soft, gray-tan to gray-pink to yellow, often with areas of haemorrhage and necrosis. One tumour (an ependymoma) was bilateral, ~ and in several other cases, the opposite ovary contained a dermoid cyst. 37'38 The ependymomas resemble similar CNS tumours, containing cells with fibrillary cytoplasmic processes that form perivascular pseudorosettes (Fig. 7), as well as occasional true rosettes. Other findings include cysts imparting a sieve-like appearance, intracystic polypoid structures, papillae, tubules and glands, ribbons or columns of cells, and psammoma bodies. 37 In occasional cases, some of the turnout cells have vacuoles that displace the nucleus. Mitotic activity has ranged from 1 to 3 per 10 high-power fields. No teratomatous elements have been identified in any of the reported cases. The primitive tumours resemble the primitive neuroectodermal tumours of the CNS, including medulloepithelioma, neuroblastoma, ependymoblastoma, and medulloblastoma) 7 They are typically highly cellular, composed of small cells with hyperchromatic, round to oval nuclei and scanty cytoplasm containing varying numbers of finely fibrillar cell processes; mitotic figures

Fig. 7--Ependymoma. Note perivascular pseudorosettes. H&E.

are numerous. The tumour cells are arranged in patternless sheets or lobules separated by fibrovascular septa. Central-lumen or central fibrillary rosettes or ribbons reminiscent of embryonal neural tube are seen to varying extents. Necrosis, which may be extensive, is commonly present. Ahnost half the tumours have contained teratomatous elements, usually minor in amount; one tumour was associated with a dermoid cyst. The anaplastic tumours are moderately to highly cellular tumours resembling glioblastoma, with areas of necrosis, sometimes surrounded by palisading tumour cells. The tumour cells are arranged in sheets or lobules and contain varying amounts of cytoplasm with eosinophilic fibrillary processes. The nuclei are more pleomorphic than in the other neuroectodermal tumours, and multinucleated giant cells are typically present. Mitotic figures are numerous, with occasional abnormal forms. Minor teratomatous foci have been present in all the cases.

The fibrillary processes and the turnout cell cytoplasm of ependymomas are typically immunoreactive for glial fibrillary acidic protein (GFAP)) v4~ Two anaplastic turnouts were also GFAP-positive) 7 Progesterone receptors were demonstrated immunohistochemically in the primary and recurrent tumour in one case of ependymoma. > The differential diagnosis of the primitive and anaplastic turnouts is generally with grade 2 or 3 immature teratomas. The latter, however, characteristically show a greater spectrum and diversity of neuroepithelial differentiation and a more extensive and varied admixture of endodermal, mesodermal, and other ectodermal tissues. Primitive tumours may also be mistaken for small-cell malignant tumours of other types that occur in the ovary of young women, including small cell carcinoma of hypercalcaemic type, malignant lymphoma and leukaemia, primary and metastatic small cell carcinoma of neuroendocrine type, metastatic melanoma, metastatic round cell sarcomas, metastatic neuroblastoma, and the desmoplastic small round cell tumour. Clinical information, thorough sampling of the tumour, and immunohistochemical staining, especially for GFAP, facilitate the differential diagnosis) 7 It should also be noted that

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CURRENT DIAGNOSTIC PATHOLOGY

ovarian tumours that are not of germ cell origin may very rarely contain neuroectodermal tissues such as malignant mesodermal mixed tumours and heterologous Sertoli-Leydig cell tumours. 37 Ovarian neuroectodermal tumours may mimic other primary and metastatic ovarian tumours, most of which are far more common. Ependymomas can be mistaken for surface epithelial-stromal tumours, specifically serous and endometrioid borderline tumours and carcinomas, sex cord-stromal tumours, including Sertoli-Leydig cell tumours and granulosa cell tumours, as well as ovarian tumours of probable Wolffian origin. The presence of the characteristic long fibrillary cytoplasmic processes, the perivascular rosettes, and GFAP-immunoreactivity confirm the diagnosis of ependymoma in problem

cases.37 The subclassification of ovarian neuroectodermal tumours has important prognostic implications. Ovarian ependymomas tend to have an indolent behaviour even when extraovarian spread has occurred. Only one tumour, which was stage III, has been fatal. 37 In the other eight cases with follow-up data, including five stage II or III tumours, the patients were alive; some had been treated successfully for one or more recurrences. 37,41 In contrast, patients with primitive and anaplastic tumours have a poor prognosis if extraowxian spread has occurred. Of those with follow-up data, only one of six patients with stage I disease died of tumour progression, whereas the 10 patients with stage II or III tumours died of their disease (eight cases) or were alive with tumour at the time of reporting (two cases). 37

SEBACEOUS TUMOURS Nine ovarian sebaceous neoplasms, which with one exception arose within a dermoid cyst, have been reported. 42~4 The women were 31-79 years of age; all of them had symptoms referrable to a pelvic mass. In one case, there was evidence of local extension into adherent rectosigmoid at the time of oophorectomy. 44 On gross examination, the tumours were usually predominantly cystic, containing solid, yellow to tan, nodular or papillary masses projecting into the lumen. All the tumours were unilateral, although the opposite ovary contained a typical dermoid cyst in some cases. On microscopic examination, the tumours are similar to cutaneous sebaceous neoplasms, including sebaceous adenoma (five cases), basal cell carcinoma with sebaceous differentiation (two cases), and sebaceous carcinoma (two cases). Abundant eosinophilic necrobiotic material with ghost outlines of mature sebaceous cells were present in at least five of the cases. One patient with basal carcinoma with sebaceous differentiation had a pelvic recurrence 2.5 years after diagnosis. In the other cases, including one case of sebaceous carcinoma associated with local extraovarian spread (see above), there were no recurrences or metastases during follow-up periods of 1-6 years. The histologic diagnosis of sebaceous tumours of the ovary is generally not difficult. The presence of large

numbers of mature spongy sebaceous cells in a tumour arising within a dermoid cyst is diagnostic. One sebaceous carcinoma, however, was originally misinterpreted as a clear cell adenocarcinoma. The diagnosis of a sebaceous neoplasm should be considered in an ovarian tumour containing spongy or basaloid cells, and in such cases evidence of an origin in a dermoid cyst should be sought.

OTHER MONODERMAL TERATOMAS Two malignant ovarian tumours resembling the retinal anlage tumour have been described. 45,46 Other rare monodermal teratomas include cysts lined predominantly or exclusively by mature glial tissue, 47 ependymal epithelium, 48 respiratory epithelium, 49 or melanotic epithelium. 5~ Epidermoid cysts, lined exclusively by mature squamous epithelium, may be monodermal teratomas, but are more likely of surface epithelial origin) 1,52

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