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Background
This is a very rare ovarian tumor which has classically been grouped in the sex cord-stromal cell tumors. These tumors are known for producing various hormones and about 1/3 of cases may present with virilization. In other patients, oligomenorrhea followed by amenorrhea may occur. Progressive masculinization and hirsuitism may also occur. However, 50% of these patients may have no endocrine symptomatology and instead have abdominal pain or swelling. Removal of the tumor results in a nomral menses in about 4 weeks.
OUTLINE
EPIDEMIOLOGY CHARACTERIZATION SYNONYMS Androblastoma INCIDENCE >0.5% of all ovarian tumors AGE RANGE-MEDIAN Mean 25 years
75%<30 years
LABORATORY/
RADIOLOGICCHARACTERIZATION Serum hormones may be elevated Elevated levels of testosterone, androstenedione Urinary hormones may be elevated Urine 17-ketosteroids
GROSS APPEARANCE/
CLINICAL VARIANTSCHARACTERIZATION General Usually unilateral
1.5% bilateralAverage size 13.5 cm ranging from 5-15 cm
Appearance Variable appearance but usually do not have as much blood filled cysts and are almost never unilocular
Poorly differentiated tumors have more necrosis or hemorrhage
HISTOLOGICAL TYPES CHARACTERIZATION SERTOLI CELL TUMORS
- Sertoli cell tumors of the ovary: a clinicopathologic and immunohistochemical study of 54 cases.
Oliva E, Alvarez T, Young RH.
From the James Wright Pathology Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Am J Surg Pathol. 2005 Feb;29(2):143-56. Abstract quote
Ovarian Sertoli cell tumors are rare, and their morphologic spectrum, behavior, and factors influencing the latter are not clearly established. They may be mimicked by many different tumors, some of them more frequent than Sertoli cell tumors; immunohistochemistry may aid in this differential, but its role has not been analyzed in a large series.
We studied the clinicopathologic features of 54 Sertoli cell tumors, including the immunohistochemical profile of 23 of them. The patients, 6 of whom had Peutz-Jeghers syndrome, ranged from 2 to 76 years of age (mean, 30 years). Eleven patients had estrogenic and 4 had androgenic manifestations. The tumors ranged from 0.8 to 30 cm, with the majority being in the range of 4 to 12 cm. They were all unilateral, usually solid, and often yellow.
The predominant microscopic pattern was tubular, seen, albeit often only focally, in all tumors; other patterns were cords or trabeculae (28), diffuse (21), pseudopapillary (4), retiform (3), islands or alveolar arrangements (3), and spindled (3). The tubules were solid or hollow with the former being somewhat more common. Delicate septa were occasionally seen and were conspicuous in areas of one tumor. The stroma was abundant in 15 tumors with marked sclerosis in 4. The cells usually had pale to occasionally densely eosinophilic cytoplasm, but 6 tumors were composed of cells with prominent foamy cytoplasm, falling in the category of "lipid-rich" Sertoli cell tumor, and one had cells with clear non-foamy cytoplasm. Forty-four tumors were stage I (42 of them were stage Ia and 2 were stage Ic), 1 was stage II, 3 were stage III, and 6 were not adequately staged. Follow-up was available for 27 patients with stage I tumors, and all were alive and well at last follow-up except for 2 patients with stage Ia and 1 with stage Ic disease. Those 3 patients had pelvic-abdominal recurrences 18, 36, and 9 months, respectively, after the initial diagnosis. Two of the three clinically malignant stage I tumors had moderate to severe cytologic atypia and brisk mitotic activity (>5 or more mitoses/10 high power fields [HPFs]), and one of these had tumor cell necrosis. Among the 10 clinically benign stage I tumors with more than 5 years of follow-up, only 3 had >5 mitoses/10 HPFs, but none had more than mild cytologic atypia and none had tumor cell necrosis. Two of the three patients with stage III disease had follow-up information and one was alive at 16 months and the second developed splenic metastases 2 years after the initial diagnosis. Two of the three stage III tumors had at least moderate cytologic atypia and brisk mitotic activity.
Immunohistochemical stains showed positivity for AE1/3-Cam5.2 in 15 of 23 tumors; Epithelial membrane antigen (EMA) was negative in all the tumors. Inhibin was positive in 18 of 22 tumors, calretinin in 10 of 20, CD99 in 19 of 22, vimentin in 17 of 18, smooth muscle actin in 4 of 18, neuron specific enolase in 8 of 16, S-100 in 2 of 20, and chromogranin was negative in all 21 cases studied. Although Sertoli cell tumors usually have a distinctive tubular pattern that facilitates the diagnosis, other patterns may occasionally predominate, causing confusion with various other primary and metastatic ovarian tumors. EMA, inhibin, and chromogranin represent the most helpful triad of immunomarkers serving to exclude two common mimics of Sertoli cell tumors (endometrioid carcinoma [inhibin-; EMA+; chromogranin-] and carcinoid tumor [inhibin-; EMA+; chromogranin+]).
Although CD99 and calretinin are often expressed in these tumors, they are much less specific and not as helpful in the differential diagnosis. Most Sertoli cell tumors are stage I, unilateral, cytologically bland, and clinically benign, but occasional examples are high stage, and about 11% of stage I tumors have worrisome histologic features that may portend an adverse outcome. The tumors typically occur in young females, sometimes children who typically present with sexual precocity, and occasional patients have Peutz-Jeghers syndrome.Well differentiated Usually a tubular pattern with a nodular architecture with fibrous bands separating lobules
Tubules lined by round to oval nuclei resembling prepubertal or atrophic testicular tubules
Minimal nuclear atypia and rare mitotic figures
Stroma with variable amounts of Leydig cells
Intermediate or Poorly Differentiated Immature Sertoli cells have small, round, oval, or angular nuclei arranged in ill-defined masses, creating a lobulated appearance
Solid and hollow tubules resembling sex cords of embryonic testis
Broad columns of Sertoli cells
Stroma may be composed of immature mesenchymal cells resembling a sarcoma
Retiform 15% of tumors
Tubular structures resembling rete testis
May have columns or ribbons of immature Sertoli cells
Encountered in tumors with intermediate, poorly differentiated, or heterologous
Ovarian Sertoli-Leydig cell tumor with retiform pattern.Moyles K, Chan YF, Hamill J, Massey R.
Histopathology Laboratory and Paediatric Surgery, Auckland, New Zealand.
Pathology 1995 Oct;27(4):371-3 Abstract quote Sertoli-Leydig cell tumors (SLCT) are sex cord-stromal tumors which exhibit testicular differentiation. They account for less than 0.2% of ovarian neoplasms in total but comprise 4% of ovarian tumors in females under 20 yrs of age. The morphological appearance of these tumors varies more widely than that of any other ovarian tumor except for the teratomas.
Histologically they are now classified into 5 categories: well-differentiated, intermediately differentiated, poorly differentiated, heterologous and retiform.
We describe the case of an ovarian Sertoli-Leydig cell tumor with retiform pattern in a 7 yr old girl.
Heterologous Occur in 20% of tumors, usually intermediate to poorly differentiated tumors
Ossifying well-differentiated Sertoli-Leydig cell tumor of the ovary.
Mooney EE, Vaidya KP, Tavassoli FA.
Department of Gynecologic and Breast Pathology, Armed Forces Institute of Pathology, Washington, DC, USA.
Ann Diagn Pathol 2000 Feb;4(1):34-8 ABSTRACT QUOTE
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.
SPECIAL STAINS/
IMMUNO-
HISTOCHEMISTRYCHARACTERIZATION GENERAL
*Department of Gynecologic and Breast Pathology, Armed Forces Institute of Pathology, Washington, DC daggerDivision of Gynecologic Pathology, Johns Hopkins Hospital, Baltimore, MD.
The main neoplasms in the differential diagnosis for primary ovarian tumors with a tubule-rich pattern are pure Sertoli cell tumor, endometrioid tumors (including borderline tumor, well-differentiated carcinoma, and the sertoliform variant of endometrioid carcinoma), and carcinoid tumor. Because traditional immunohistochemical markers [pan-cytokeratin (pan-CK), low molecular weight cytokeratin (CK8/18), epithelial membrane antigen (EMA), inhibin, calretinin, CD99, chromogranin, and synaptophysin] can occasionally have diagnostic limitations, the goal of this study was to determine whether or not any alternative markers [cytokeratin 7 (CK7), estrogen receptor (ER), progesterone receptor (PR), CD10, and CD56] have better diagnostic utility when compared with traditional markers for this differential diagnosis.
Immunohistochemical stains for alternative, as well as traditional, markers were performed on the following primary ovarian tumors: pure Sertoli cell tumor (n=40), endometrioid borderline tumor (n=38), sertoliform endometrioid carcinoma (n=13), well-differentiated endometrioid carcinoma (n=27), and carcinoid tumor (n=42). Extent and intensity of immunostaining were semiquantitatively scored. In addition, immunohistochemical composite scores (ICSs) in positive cases were calculated on the basis of the combination of extent and intensity scores. Cytokeratin 7 (CK7) was positive in 97% of endometrioid tumors, 13% of Sertoli cell tumors, and 24% of carcinoid tumors. The differences in the mean ICSs for endometrioid tumors versus Sertoli cell tumor or carcinoid tumor were statistically significant (P values ranging from <0.001 to 0.018). ER and PR were positive in 87% and 86% of endometrioid tumors, 8% and 13% of Sertoli cell tumors, and 2% each of carcinoid tumors, respectively. The differences in the mean ICSs for endometrioid tumors versus Sertoli cell tumor were statistically significant (P values ranging from <0.001 to 0.012). Among the epithelial markers, EMA seemed to be the most discriminatory but only slightly better than CK7, ER, or PR. Pan-CK and CK8/18 were not helpful. CD10 showed overlapping patterns of expression in all categories of tumors. Among the sex cord markers, CD10 was markedly less useful than inhibin or calretinin; CD99 was not discriminatory. CD56 showed overlapping patterns of expression in all categories of tumors. Among the neuroendocrine markers, CD56 was less useful than chromogranin or synaptophysin.
When traditional immunohistochemical markers are problematic for the differential diagnosis of ovarian Sertoli cell tumor versus endometrioid tumors versus carcinoid tumor, adding CK7, ER, and/or PR to a panel of markers can be helpful. Endometrioid tumors more frequently express CK7, ER, and PR and show a greater extent of immunostaining in contrast to Sertoli cell tumor and carcinoid tumor. Compared with traditional epithelial markers, CK7, ER, and PR are nearly as advantageous as EMA. Inhibin is the most discriminatory sex cord marker, and CD10 is not helpful in the differential diagnosis. Chromogranin and synaptophysin are excellent discriminatory markers for carcinoid tumor, and CD56 is neither sufficiently sensitive nor specific enough for this differential diagnosis to warrant its use in routine practice.
Ovarian sex cord-stromal tumors: an immunohistochemical study including a comparison of calretinin and inhibin.Deavers MT, Malpica A, Liu J, Broaddus R, Silva EG.
Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Mod Pathol. 2003 Jun;16(6):584-90. Abstract quote Because ovarian sex cord-stromal tumors (SCST) are morphologically heterogeneous neoplasms that are relatively infrequently encountered, their diagnosis can be difficult. Immunohistochemical staining may be useful for establishing the diagnosis in problematic cases.
We studied 53 ovarian SCSTs to characterize their immunohistochemical staining pattern: 17 adult granulosa cell tumors (AGCTs), 4 juvenile granulosa cell tumors (JGCTs), 3 sex cord tumors with annular tubules (SCTATs), 9 Sertoli-Leydig cell tumors (SLCTs), 10 fibromas, 5 fibrothecomas (FTs), and 5 thecomas. In 8 of the 53 cases, the tissue studied was from a metastatic site. The immunopanel included calretinin, inhibin, WT1, cytokeratin cocktail, epithelial membrane antigen (EMA), and cytokeratin 5/6 (CK5/6). The fibromas and FTs were also tested with CD10. The extent of staining was assessed in a semiquantitative fashion and ranked on a scale of 0 through 4+. All of the tumors, except for 1 metastatic SLCT, were positive for calretinin. Forty-five of the cases (85%) stained for inhibin; 1 metastatic AGCT, 3 fibromas, and 4 FTs were negative. WT1 was present in 39 tumors (74%), with expression most prominent in the SLCTs. The cytokeratin cocktail stained 23 of the 53 tumors (43%), whereas just 1 tumor was positive for EMA (1+ in a JGCT). All tumors were negative for CK5/6, and the 15 fibromas and FTs were negative for CD10.
We conclude that because cytokeratin is frequently expressed by SCSTs, in particular by granulosa cell tumors, SLCTs, and SCTATs, the inclusion of EMA in a panel may help to exclude epithelial neoplasms. In addition, WT1, present in normal granulosa cells, is expressed by a majority of SCSTs. Finally, these results demonstrate that calretinin is at least as sensitive as inhibin for ovarian SCSTs overall and that it is more sensitive than inhibin for fibromas and FTs.CALRETININ Immunohistochemical staining for calretinin is useful in the diagnosis of ovarian sex cord-stromal tumours.
McCluggage WG, Maxwell P.
Department of Pathology, Royal Group of Hospitals Trust, Belfast and The Queen's University of Belfast, Grosvenor Road, Belfast BT12 6BL, Northern Ireland.
Histopathology 2001 May;38(5):403-8 Abstract quote
AIMS: Ovarian sex cord-stromal tumours are a heterogeneous group of neoplasms which may be confused morphologically with a wide variety of tumours. Calretinin positivity has previously been demonstrated in a small number of ovarian sex cord-stromal tumours. The aim of this study was to investigate calretinin staining in a series of these tumours and their histological mimics in order to determine the value of calretinin staining in a diagnostic setting.
METHODS AND RESULTS: Seventy-two neoplasms, including 37 ovarian sex cord-stromal tumours and 35 miscellaneous neoplasms which may enter into the differential diagnosis, were stained with a commercially available polyclonal antibody against calretinin. All sex cord-stromal tumours exhibited positivity except for a single fibrothecoma. In this group of tumours staining was generally diffuse and strong. Small numbers of the miscellaneous group of neoplasms exhibited positivity but this tended to be focal and weak, although this was not always the case. There was consistent strong positive staining of granulosa cells in follicular cysts and corpora lutea. There was also positive staining of luteinized stromal cells in two cases of ovarian stromal hyperplasia and hyperthecosis.
CONCLUSIONS: Calretinin is a sensitive immunohistochemical marker of ovarian sex cord-stromal tumours and may be useful in a diagnostic setting. However, the value is somewhat limited since occasional neoplasms which enter into the morphological differential diagnosis may be positive. Be that as it may, calretinin positivity may be of value in the diagnosis of an ovarian sex cord-stromal tumour and its differentiation from other neoplasms. In this regard, calretinin should always be used as part of a larger panel.
INHIBIN
Inhibin immunohistochemical staining: a practical approach for the surgical pathologist in the diagnoses of ovarian sex cord-stromal tumors.Zheng W, Senturk BZ, Parkash V.
Adv Anat Pathol 2003 Jan;10(1):27-38 Abstract quote Through a brief introduction of inhibin history, characteristics of the antibody against inhibin, and normal tissue distribution of alpha-inhibin expression, this comprehensive review focuses on a practical approach to using alpha-inhibin in the differential diagnosis of ovarian sex cord-stromal tumors (SCSTs). Alpha-inhibin has become a most useful immunohistochemical marker of gonadal SCST, regardless if the tumors are primary, recurrent, or metastatic. However, pathologic diagnosis of individual SCST is still based largely on morphologic criteria.
Alpha-inhibin immunohistochemical (IHC) staining should be used only when a difficult morphologic diagnosis is encountered. In this perspective, alpha-inhibin and other properly selected markers should be ordered at the same time. This is simply because alpha-inhibin is not specific for SCSTs.
Caution should be exercised in the interpretation of alpha-inhibin-positive cells, because a wide variety of primary and metastatic ovarian tumors may contain significant numbers of alpha-inhibin-positive stromal cells. As with other immunohistochemical stains, a panel of stains and comparison with the corresponding hematoxylin and eosin (H&E) slides is necessary, especially when staining patterns and cellular localization are in question. The antibody will not help to differentiate tumors within the category of SCST. The pattern or the intensity of staining in SCSTs does not predict tumor behavior, although there is a tendency of loss of alpha-inhibin expression in poorly differentiated Sertoli or Sertoli-Leydig cell tumors.
In cases where metastatic granulosa or Sertoli-Leydig cell tumors are a concern, positive alpha-inhibin staining is diagnostic, but a negative result does not rule out metastatic disease. Calretinin has been recently recognized as a more sensitive, but less specific marker for SCSTs and it may be used to recognize an inhibin-negative SCST.
In this review, we have listed nine of the most commonly encountered clinical scenarios where alpha-inhibin and other markers could be used in diagnostic surgical pathology of ovarian tumors.
Use of monoclonal antibody against human inhibin as a marker for sex cord-stromal tumors of the ovary.Rishi M, Howard LN, Bratthauer GL, Tavassoli FA.
Department of Gynecologic and Breast Pathology, Armed Forces Institute of Pathology, Washington DC, USA.
Am J Surg Pathol 1997 May;21(5):583-9 Abstract quote Inhibin is a glycoprotein hormone produced by normal ovarian granulosa cells and testicular sertoli cells. In the ovary, it inhibits the secretion of follicle-stimulating hormone. Patients with granulosa cell tumors (GCT) have elevated serum levels of inhibin and this finding has been used to detect recurrent tumor.
This study attempts to determine whether inhibin antibody (IAB) can preferentially mark GCT and Sertoli-cell or Sertoli-Leydig cell tumors (SCT) in paraffin-embedded tissues and facilitate distinction of GCT from small cell carcinoma of hypercalcemic type (SCC), SCT from Sertoliform endometrioid carcinoma (SEC), and primitive gonadal-stromal tumors from a variety of poorly differentiated neoplasms. Applying microwave-enhanced immunohistochemistry, a total of 126 paraffin-embedded and microwave-enhanced archival ovarian tumors and tissues were studied by using monoclonal IAB.
The tumors included 32 adult GCT, 7 juvenile GCT, 4 metastatic GCT, 8 SCT, 7 SCC, 6 primitive gonadal stromal tumors (PGST), 5 fibrothecomas, 6 lipid cell tumors (LCT), 5 extrauterine endometrial stromal sarcomas (ESS), 5 hemangiopericytomas (HPC), 1 metastatic malignant melanoma, 1 metastatic malignant lymphoma, and 27 epithelial tumors including 8 SEC, 5 mucinous tumors, and 4 Brenner tumors. Seven pregnancy luteomas (nodular theca lutein hyperplasia of pregnancy), 3 corpora lutea and 2 ovarian follicles were also studied. The intensity of immunostaining was scored from one to three and the percentage of the immunoreactive tumor cells was determined and expressed in 10% increments.
Among 32 adult GCT, 31 (97%) tumors reacted positively with IAB. The percent of positive cells ranged from 30% to 100% (average 80%). Similarly, all four metastatic GCT, 7 juvenile GCT and 4 of 5 fibrothecomas were immunoreactive with monoclonal IAB. Seven of 8 (88%) SCT, 5 of 6 (83%) PGST, all 6 LCT, 7 pregnancy luteomas, 3 corpora lutea and the 2 ovarian follicles were also positive with IAB. The most intense positivity was observed in luteinized stromal cells regardless of tumor type.
No immunoreactivity was observed in any of the 7 SCC, 5 ESS, 5 HPC, 1 metastatic malignant melanoma, 1 metastatic malignant lymphoma and the epithelial component of all 27 epithelial tumors including 8 SEC. Among the mucinous tumors of the ovary, however, 3 tumors with luteinized stromal cells showed immunoreactivity in these cells, but no positivity was seen in the mucinous epithelium.
We conclude that IAB is an excellent marker for sex cord differentiation in ovarian tumors. It can be used effectively in the diagnosis of GCT and its distinction from epithelial neoplasms particularly SCC. The IAB may also be helpful in differentiating LCT from epithelial malignancies. However, it cannot be used to distinguish GCT from SCT.
Inhibin immunohistochemistry applied to ovarian neoplasms: a novel, effective, diagnostic tool.Costa MJ, Ames PF, Walls J, Roth LM.
University of California-Davis Medical Center, Sacramento 95817, USA.
Hum Pathol 1997 Nov;28(11):1247-54 Abstract quote Immunohistochemistry using monoclonal antibodies against human inhibin, a peptide hormone produced by ovarian granulosa cells to inhibit follicle-stimulating hormone (FSH), has been recently applied to diagnostic anatomic pathology.
This investigation hypothesizes that inhibin immunohistochemistry will aid in the crucial clinical distinction between sex cord-stromal and other primary ovarian neoplasms. Available H&E slides and clinical information from a retrospective surgical series of 186 primary ovarian tumors were reviewed to verify diagnoses, and representative paraffin sections were immunostained with anti-inhibin (R1 monoclonal, Serotec, Kidlington, Oxford, UK). Immunoreactivity was graded as weak/strong (W/S), and the proportion of strong staining cells was coded as follows: S1 = <10%, S2 = 10%-50%, S3 = >50%, respectively. Inhibin immunoreactivity for 137 sex cord-stromal lesions was as follows: 100% of 66 granulosa cell tumors: 80% S3, 20% S2; 100% of 17 Sertoli-stromal tumors: 90% S3, 10% S2; 100% of 13 hyperplastic follicular/stromal lesions: 90% S3, 10% S2; 100% of six steroid cell tumors: 100% S3; 90% of 18 thecomas: 40% S3, 10% S2, 10% S1, 30% W; 0% of 12 fibromas, three myxomas, and two sclerosing stromal tumors. None (0 of 49) of the other ovarian neoplasms exhibited inhibin: 22 carcinomas, 12 carcinosarcomas, seven small cell carcinomas, six germ cell tumors, and two lymphomas.
In the typical case, the distinction between sex cord-stromal and other ovarian neoplasms requires nothing more than routine pathological examination. In diagnostically challenging cases, our data indicate that inhibin immunohistochemistry is a very useful adjunct because granulosa and sertoli-stromal tumors are positive whereas other potential mimickers have been negative thus far.
WT1
*Department of Pathology, Magee-Womens Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA †Department of Gynecologic and Breast Pathology, Armed Forces Institute of Pathology, Washington, DC ‡Division of Gynecologic Pathology, Johns Hopkins Hospital, Baltimore, MD.
WT1, the Wilms tumor gene product, can be expressed in various tumors from different anatomic sites, including some types of ovarian tumors. Regarding the latter, most studies have focused on surface epithelial-stromal tumors in which serous carcinomas are usually positive and endometrioid carcinomas are negative. Very few studies have specifically investigated this marker in ovarian sex cord-stromal tumors; however, limited data in the literature suggest that WT1 may be frequently expressed in sex cord-stromal tumors. As pure Sertoli cell tumor can be in the histologic differential diagnosis of endometrioid tumors (particularly borderline tumor and carcinoma) and carcinoid, immunostaining for WT1 might be of diagnostic value.
Immunohistochemical staining for WT1 was performed in 108 ovarian tumors: pure Sertoli cell tumor (n=26), endometrioid borderline tumor (n=25), classic well-differentiated endometrioid carcinoma (n=23), sertoliform endometrioid carcinoma (n=12), and carcinoid (n=22). Additionally, inhibin and calretinin immunostaining were performed in all cases of Sertoli cell tumor for purposes of comparing expression with WT1. Extent of immunostaining was scored on a 0 to 4+ semiquantitative scale, and immunohistochemical composite scores based on a combination of extent and intensity of immunostaining were calculated in positive cases (possible range, 1 to 12). Nuclear expression of WT1 was present in 96% of Sertoli cell tumors, 16% of endometrioid borderline tumors, 13% of classic well-differentiated endometrioid carcinomas, 25% of sertoliform endometrioid carcinomas, and 0% of carcinoids. In Sertoli cell tumors, expression was diffuse (>50% of positive cells) in all positive cases. When positive in the non-Sertoli cell tumors, the extent of expression tended to be focal to patchy (50% or less positive cells). In Sertoli cell tumors, inhibin and calretinin were expressed in 96% and 54% of cases, respectively. The extent of expression of inhibin tended to be diffuse, similar to WT1; however, the extent of immunostaining for calretinin tended to be focal to patchy. The immunohistochemical composite scores for WT1, inhibin, and calretinin were 11.2, 7.6, and 4.8, respectively. Coordinate patterns for the extent of expression of WT1, inhibin, and calretinin in pure Sertoli cell tumor showed that all 3 markers were positive in 54% of cases; however, 42% were positive for WT1 and inhibin but negative for calretinin. In cases positive for both WT1 and inhibin, expression of both markers was diffuse in 84% of cases, but WT1 was diffuse while inhibin was focal to patchy in 16% of cases.
We conclude that ovarian Sertoli cell tumor should be added to the growing list of WT1-positive tumors. This marker is useful for the distinction of Sertoli cell tumor from endometrioid tumors and carcinoid. The diagnostic utility of WT1 in Sertoli cell tumor is similar to inhibin but better than that of calretinin.
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES UNCLASSIFIED GONADAL STROMAL TUMORS
Unclassified ovarian gonadal stromal tumors. A clinicopathologic study of 32 cases.Seidman JD.
Department of Gynecologic and Breast Pathology, Armed Forces Institute of Pathology, Washington, D.C. 20010, USA.
Am J Surg Pathol 1996 Jun;20(6):699-706 Abstract quote Approximately 10% of gonadal stromal (sex cord-stromal) tumors of the ovary are difficult to classify. In most of these cases, the differential diagnosis is between granulosa and Sertoli-Leydig types.
We studied 32 such neoplasms. The tumors were divided into two groups: Group 1 consisted of tumors with a predominance of a primitive spindle-cell stroma without specific differentiation, and group 2 consisted of tumors with a predominance of cords, trabecula, or tubules with features suggestive of or characteristics of both granulosa and Sertoli-Leydig cell differentiation in different areas. All tumors had overall features that did not permit definitive placement into granulosa or Sertoli-Leydig categories. There were 18 group 1 tumors and 14 group 2 tumors. The mean patient age was 49 years.
The International Federation of Gynecology and Obstetrics (FIGO) stage was known in 12 patients, all of whom were in stage I. Survival data were available for 17 patients, whose follow-up was a mean of 8 years of until death. There were three deaths, one of which was of unrelated causes. the 5- and 10-year corrected actuarial survival rates were 92% and 74%. The number of patients was too small to make meaningful comparisons between the two groups.
We concluded that the behavior of these unclassified tumors is similar to that of granulosa and Sertoli-Leydig tumors, with a favorable prognosis when confined to the ovaries.
PROGNOSIS AND TREATMENT CHARACTERIZATION Prognostic Factors Stage of tumor is important
Stage Iai in 80% of tumors
Tumor rupture or involves the external surface of the ovary in 12%
Ascites in 4%Spread beyond the ovary within the pelvis or upper abdomen in 2.5%
Poorly differentiated were more often ruptured or presented at a higher stage
Survival In Stage I tumors:
Well differentiated tumors-0% malignant
Intermediate-11% malignant
Poorly differentiated-59% malignant
Heterologous elements-19% malignant
Retiform tumors with intermediate differentiation-25% malignantRecurrence 66% of malignant tumors recurred within 1 years
6.6% recurred after 5 yearsMetastasis Lung, scalp, supraclavicular lymph nodes, liver TREATMENT Unilateral salpingoophorectomy
If poorly differentiated elements or heterologous elements are present, adjuvant therapy may be indicated with radiation or combination chemotherapyTAH-BSO
May consider adjuvant therapyCHEMOTHERAPY
Bleomycin, etoposide, and cisplatin combination therapy of ovarian granulosa cell tumors and other stromal malignancies: A Gynecologic Oncology Group study.Homesley HD, Bundy BN, Hurteau JA, Roth LM.
Brookview Research Inc., Winston-Salem, North Carolina, 27103, USA
Gynecol Oncol 1999 Feb;72(2):131-7 Abstract quote OBJECTIVES: The objectives of this study were to assess efficacy and toxicity of the combination of bleomycin, etoposide, and cisplatin (BEP) in this Phase II trial as first-line therapy for ovarian stromal malignancies.
METHODS: Patients with incompletely resected Stages II-IV or recurrent cancer underwent surgical debulking. There were two bleomycin-related deaths early in the trial; thus, the initial schedule of bleomycin (20 units/m2 x 9 weeks for a maximum dose of </=30 units x 9) was changed, without subsequent mortality. The final dose schedule was 20 units/m2 bleomycin iv push day 1 every 3 weeks x 4, 75 mg/m2 etoposide days 1-5 every 3 weeks x 4 and 20 mg/m2 cisplatin days 1-5 every 3 weeks x 4. The frequency of negative second-look surgery was the primary outcome measure.
RESULTS: Seventy-five women were entered; 18 were excluded. Grade 4 myelotoxicity occurred in 61% of the patients. The end point used for response was negative second-look laparotomy. Thirty-seven percent (14/38) of the patients undergoing second-look laparotomy had negative findings. The six complete responders were of long median duration (24.4 months). Patients with measurable disease were at the highest risk of progression and death.
CONCLUSIONS: BEP appears to be an active combination regimen for first-line chemotherapy of malignant tumors of the ovarian stroma. Myelotoxicity was tolerable.
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Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
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