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Robert H Young

Publications and source records attributed to Robert H Young.

At least 19 recordsLinked to original sources
PubMed2007

Oxyphilic adenomatoid tumor of the ovary: a case report with discussion of the differential diagnosis of ovarian tumors with vacuoles and related spaces.

We describe an unusual example of ovarian adenomatoid tumor that was an incidental finding in the ovary of a 52-year-old woman and was characterized by cells with abundant eosinophilic cytoplasm, an occasional feature of the adenomatoid tumor but one that, in an ovarian example, may cause added diagnostic confusion to that already engendered by the rarity of this neoplasm in the ovary. The typical numerous small vacuoles of the neoplasm sometimes had the appearance of signet ring cells. These 2 features (oxyphil and signet ring cells) caused a broad differential. Tumor cells were positive with broad-spectrum cytokeratins as well as mesothelial markers CK5/6, WT1, and calretinin. In reporting this case, we focus on the differential diagnosis of ovarian neoplasms and tumorlike conditions with vacuoles and related spaces, a topic that embraces many diverse entities.

Adenomatoid Tumor↗
PubMed2006

Autoimplants in serous borderline tumors of the ovary: a clinicopathologic study of 30 cases of a process to be distinguished from serous adenocarcinoma.

The clinical and pathologic features of serous borderline tumors (SBTs) with autoimplants (AIs) were studied with emphasis on their relation to survival, ovarian SBT with a micropapillary pattern, and their distinction from serous adenocarcinoma. The 30 patients ranged in age from 17 to 70 years (mean, 35.8 years). Two had stage I disease, 10 had stage II disease, and 18 had stage III disease. Twenty-five patients had bilateral ovarian tumors. In 28 cases, AIs were present on the surface of the neoplasm or between exophytic surface tumor papillae; in 2 cases, AIs were between papillae within intracystic tumor. The AIs consisted of single cells or glands and clusters of cells with mild to moderate nuclear atypia within a fibroblastic stroma; the stroma dominated over the epithelium in extent within the AI. In many cases, the epithelial cells in the AI had abundant eosinophilic cytoplasm. All but 2 of the patients had coexisting noninvasive peritoneal implants; 3 of them also had invasive peritoneal implants. Six of the SBTs had a micropapillary pattern; 3 of these were stage III and 3 stage II tumors. Clinical follow-up was available for 11 patients. Eight were alive and well after 4 to 7 years (mean, 5 years); 3 of these patients had stage II disease and 5 had stage III disease. Three were dead of disease after 7 to 12 years (mean, 9 years). Two patients who died of disease had stage III disease, and 1 of them had invasive implants. The third patient had stage II disease, invasive implants, and the tumor was of the micropapillary type. Our study indicates that the majority of patients with SBT with AI have stage II or III disease and abundant exophytic tumor. SBTs with AI had a micropapillary pattern in 20% of the cases. AIs do not appear to have an adverse impact on survival when controlled for peritoneal implant type and for this reason must be distinguished from true stromal invasion in serous carcinoma, a misdiagnosis sometimes made, or seriously entertained, initially in these cases. Features that favor AI over carcinoma arising in an SBT are 1) a location between tumor papillae or on the ovarian surface 2) a predominance of stroma over epithelial cells, and 3) the "borderline" cytologic appearance of epithelial cells.

Adolescent↗
PubMed2006

Cellular fibromas of the ovary: a study of 75 cases including 40 mitotically active tumors emphasizing their distinction from fibrosarcoma.

Cellular fibroblastic tumors of the ovary are currently classified as either cellular fibroma (CF) or fibrosarcoma. The former are characterized by bland nuclei, 3 or fewer mitotic figures per 10 high-power fields (MFs/10 HPFs), and a low malignant potential, whereas fibrosarcomas usually have severe nuclear atypia, > or = 4 MFs/10 HPFs, and an aggressive clinical course. The prognosis of cellular fibromatous tumors with > or = 4 MFs/10 HPFs and low-grade cytology is not established and it is the purpose of this study to investigate that aspect. It has been our anecdotal experience that otherwise typical CFs with > or = 4 MFs/10 HPFs usually have a benign clinical course, suggesting that such tumors should be regarded as "mitotically active cellular fibroma" (MACF) rather than fibrosarcoma. Seventy-five cellular fibromatous neoplasms were analyzed to determine their clinicopathologic features and the appropriateness of "MACF" as a designation for otherwise typical CFs with > or = 4 MFs/10 HPFs. The mean age of patients with CF (n = 35, 0 to 3 MFs/10 HPFs) and MACF (n = 40, > or = 4 MFs/10 HPFs) was 51 and 41 years, respectively. Patients most commonly presented with symptoms related to a pelvic mass. All tumors were unilateral. The mean tumor size of CFs was 8.0 cm and 9.4 cm for MACFs. The majority of the tumors were solid; approximately one-third of them had a cystic component. Ovarian surface adhesions, involvement of the ovarian surface, or both, was present in 6% of CFs and 10% of MACFs. Eleven percent of CFs and 13% of MACFs were associated with extraovarian involvement. All tumors consisted of cellular, intersecting bundles of spindle cells with bland nuclear features. The mean highest mitotic count for MACFs was 6.7 MFs/10 HPFs (range 4 to 19 MFs/10 HPFs). Follow-up of 3 months to 12 years (mean 4.75 y) was available in 18 of the 40 patients with MACFs and was uneventful in all cases. We conclude that cellular fibromatous neoplasms with bland cytology and elevated mitotic counts are associated with favorable patient outcome and should be diagnosed as MACF rather than fibrosarcoma, which usually have moderate to severe atypia and elevated mitotic rates. As prior observations have shown that even typical CFs can occasionally recur locally, particularly if they are associated with rupture or adherence, long-term follow-up for patients with CFs and MACFs is appropriate.

Adult↗
PubMed2006

From krukenberg to today: the ever present problems posed by metastatic tumors in the ovary: part I. Historical perspective, general principles, mucinous tumors including the krukenberg tumor.

This review considers historical aspects of metastatic tumors to the ovary, general principles that aid in their evaluation, and metastatic mucinous tumors, including the Krukenberg tumor. The historical timeline on the Krukenberg tumor dates back to the legendary Sir James Paget and the story is followed through the well-known, albeit flawed, contribution of Friedrich Krukenberg and others who have contributed important papers over the years, including the overlooked contribution of the French investigator Gauthier-Villars. Knowledge of metastatic colorectal carcinoma is traced back to the famed British surgeon Sir John Bland-Sutton and followed through to more recent contributions, including the important one of Lash and Hart. Contributions on mucinous tumors conclude the historical perspective, note being made of the recent evidence suggesting that the long held contention of Dr Robert E. Scully that ovarian mucinous tumors in patients with pseudomyxoma peritonei usually originate from the appendix is correct. The section on general principles highlights the many clinical, gross, microscopic, and special techniques such as immunohistochemistry that may aid in determining that an ovarian tumor is metastatic with emphasis on the first 3 mentioned aspects. Problematic features such as a tendency for metastatic tumors to be cystic, even when the primary tumors are not, and for many metastatic tumors to mature in the ovary (so-called maturation phenomenon), are emphasized. Of the many helpful findings that resolve the problem, the characteristic features of surface implants are highlighted. The contribution on the Krukenberg tumor reviews the varied microscopy of this tumor pointing out that the well-known pattern of signet-ring cells in a cellular stroma, albeit characteristic, is often not striking and frequently overshadowed by other microscopic features. The latter include, in many cases, a rather unique microcystic pattern. The final portion of the essay reviews mucinous tumors of non-Krukenberg type, beginning with those that originate from the appendix. The appendiceal neoplasms have distinctive features in most cases being particularly well differentiated, and this is also seen in their ovarian metastases. Other mucinous tumors that commonly simulate closely metastatic neoplasms, include those from the pancreas in particular, but also diverse other sites, are then reviewed.

Adenocarcinoma, Mucinous↗
PubMed2006

Use of histone deacetylase 8 (HDAC8), a new marker of smooth muscle differentiation, in the classification of mesenchymal tumors of the uterus.

UNLABELLED: Uterine smooth muscle tumors (SMTs) are usually recognized on the basis of their routine morphologic features; however, their distinction from endometrial stromal tumors (ESTs), the second most common mesenchymal tumor of the uterus, is sometimes problematic. Histone deacetylases (HDACs) were originally identified as nuclear enzymes regulating histone acetylation. We have recently shown that in normal human tissues, HDAC8 is exclusively expressed in the cytoplasm of cells showing smooth muscle differentiation. In this study, we examined HDAC8 expression in SMTs and ESTs of the uterus to determine whether HDAC8 may be a useful diagnostic tool in the classification of problematic uterine mesenchymal tumors. HDAC8 immunohistochemical staining was performed in 15 leiomyomas (LMs), 9 highly cellular leiomyomas (HCLs), 8 epithelioid SMTs, 13 leiomyosarcomas (LMSs), and 17 ESTs, including 3 with sex-cord differentiation and 5 with smooth muscle differentiation. All tumors were also stained for other smooth muscle markers (desmin, h-caldesmon, smooth muscle actin [SMA], smooth muscle myosin heavy chain) and for CD10. All LMs had moderate to strong expression of all smooth muscle markers. HDAC8 was detected in 8 of 9 HCLs and in all epithelioid SMTs (8 of 8); however, it was weak in 4 epithelioid SMTs. In contrast, desmin, h-caldesmon and smooth muscle myosin were positive in only 2 of 8, 1 of 8 and 4 of 8 epithelioid SMTs, respectively. All smooth muscle markers had similar frequency of staining in LMSs; however, HDAC8 showed overall moderate intensity compared with other smooth muscle markers, which showed stronger staining. HDAC8, h-caldesmon, and smooth muscle myosin did not stain conventional areas of ESTs or ESTs with sex-cord differentiation, whereas SMA and desmin were positive in those areas in 4 of 12 and 3 of 12 ESTs, respectively. Areas of smooth muscle differentiation in ESTs were positive for HDAC8 in all cases, but they were less constantly positive for the other smooth muscle markers. CD10 was expressed in most ESTs (14 of 17), but it was also positive in 15 of 45 SMTs. IN CONCLUSION: 1) HDAC8 seems to be a specific marker of SM differentiation because conventional ESTs and ESTs with sex-cord differentiation are negative for HDAC8, whereas areas of smooth muscle differentiation in these tumors are consistently positive; 2) HDAC8 gives similar results to those obtained with desmin, h-caldesmon, and smooth muscle myosin in both LMs and LMSs, although the staining for HDAC8 in LMSs tends to be less intense; 3) HDAC8 may be a more sensitive marker than desmin and h-caldesmon in epithelioid SMTs. Thus, HDAC8 detection may be useful in helping the differential diagnosis of uterine mesenchymal tumors.

Biomarkers, Tumor↗
PubMed2006

Paraganglioma of the ovary: report of three cases of a rare ovarian neoplasm, including two exhibiting inhibin positivity.

Paraganglioma is one of the rarest neoplasms to involve the ovary, whether primary or metastatic, with only two previous reports. We describe three examples that occurred in patients 22, 58, and 68 years of age. Two patients had hypertension. Two tumors involved the left ovary and one the right ovary; they ranged from 8 to 22 cm, were solid, and were tan, brown, or yellow. One tumor was confined to the ovary; in the second case, there were tumor deposits on the posterior surface of the uterus and the contralateral ovary; in the other case, there was peri-aortic lymph node involvement and peritoneal deposits. In all cases, however, radiologic investigations did not reveal an alternative primary site. On microscopic examination, all three tumors showed a predominantly nested "zellballen" pattern with groups of cells surrounded by a vascular stroma. Tumor cells largely had abundant granular eosinophilic cytoplasm with, in 2 cases, focal clear cell areas. In 1 case, bizarre tumor giant cells were present. Immunohistochemically, all neoplasms were cytokeratin negative and diffusely positive with neuroendocrine markers. In 1 case, there was an S-100-positive population of sustentacular cells. Two cases were positive for inhibin, one focal and one diffuse, and the other was focally positive for calretinin. Electron microscopy performed in 2 cases revealed dense core neuroendocrine granules. One patient has been followed up for 15 years and is alive and well. Although metastatic spread from an undetected primary outside the ovary cannot be totally excluded for the 2 cases with extraovarian disease, we think that the neoplasms most likely represent primary ovarian paragangliomas. Because various neoplasms in the sex cord-stromal and steroid categories are likely to enter into the differential diagnosis, inhibin and calretinin positivity represents a significant potential diagnostic pitfall. The differential is broad and may include many other ovarian tumors, particularly those with an oxyphilic cell type. Possible theories of histogenesis of primary ovarian paraganglioma include an origin from extra-adrenal paraganglia in the region of the ovary or unidirectional differentiation within a teratoma.

Adenocarcinoma↗
PubMed2006

Krukenberg tumors of the ovary: a clinicopathologic analysis of 120 cases with emphasis on their variable pathologic manifestations.

120 Krukenberg tumors were analyzed with emphasis on their wide microscopic spectrum and resultant problems in differential diagnosis. The patients ranged from 13 to 84 years (average, 45 years) with 43% of them under 40 years. Abdominal swelling or pain usually accounted for the clinical presentation, but 17 had abnormal vaginal bleeding, 4 had virilization, and 4 had hirsutism without virilization. Ascites was present in 43% of the cases. Sixty-three percent of the tumors were documented to be bilateral, but both ovaries were not always removed or rigorously examined microscopically. The mean diameter of the tumors was 10.4 cm, and they typically had intact, bosselated external surfaces without adhesions. The sectioned surfaces were typically solid and firm to edematous to gelatinous; one third of the tumors also had cysts. Microscopic examination showed great variation from case to case and within individual neoplasms. Multiple nodules separated by normal stroma were seen in small neoplasms and focally in many larger ones. The tumors were often more cellular at their periphery and edematous to gelatinous centrally. An irregular distribution of cellular and less cellular areas often imparted a pseudolobular pattern. The cellularity of the stroma ranged from densely cellular to paucicellular; the latter regions ranged from edematous to mucoid. The overall morphology varied according to the prominence of signet-ring cells, extracellular mucin, edema, and various epithelial patterns. Signet-ring cells were numerous in most neoplasms (and by definition occupied at least 10% of the neoplasm) but were often absent or inconspicuous in significant areas of them. The signet-ring cells typically had modest but sometimes copious amounts of pale to basophilic cytoplasm; occasionally, it was eosinophilic. The signet-ring cells varied widely in their arrangement, growing singly, in clusters, forming confluent masses or pseudo-tubular arrays or lining part of all of a true tubule. Small glands and tubules were common, often resembling microcysts (when the lining cells were flattened) or Sertoli tubules; mucinous glands and cysts and medium-sized to large intestinal-type glands were also relatively common, particularly the latter. Extracellular mucin was often conspicuous and, when associated with scant acellular collagenous stroma, gave a distinctive appearance referred to by us as "feathery degeneration." Stromal luteinization was present in the tumors of the 8 pregnant patients and was seen in 14% of the nonpregnant patients. Unusual features that complicated the microscopic picture included diffuse sheets or other arrangements of mucin-free indifferent cells, squamous cells, clear cells, transitional cells, and corded, trabecular, and insular patterns. Vascular space invasion was common. Two thirds of the primary carcinomas were detected synchronously with, or subsequent to, detection of the Krukenberg tumor compounding the diagnostic difficulty posed by the cases. Two thirds of the primary tumors were in the stomach; other primary sites in order of frequency were appendix, colon, breast, small intestine, rectum, gallbladder, and urinary bladder. Our observations emphasize that the microscopic spectrum of the Krukenberg tumor is broader that often presented in the literature, in particular tubules, glands, and cysts often being present, and the wide pathologic differential diagnosis is discussed.

Adolescent↗
PubMed2006

Ovarian metastases of intestinal-type gastric carcinoma: A clinicopathologic study of 4 cases with contrasting features to those of the Krukenberg tumor.

Ovarian metastases of intestinal-type gastric adenocarcinomas are rare, and information on them is very limited compared with that on signet-ring cell carcinomas that result in the Krukenberg tumor. Four cases are reported herein. The patients averaged 55 years of age. In 3 patients, the ovarian metastases were identified several to 21 months after the diagnosis of the gastric primary, and the tumors were synchronous in the fourth. Two tumors were bilateral, 1 unilateral, and for 1, the laterality was unknown. The ovarian tumors were characteristically solid and cystic, with multinodular growth in 2. In 2 cases, the ovarian tumors had a pseudoendometrioid morphology with tubulo-glandular, cribriform, and papillary patterns; they also had focal trabecular and insular patterns. Prominent necrosis was present, including segmental and intraluminal "dirty" necrosis. In the other 2 cases, the ovarian tumors had a mucinous appearance, 1 being dominantly cystic with occasional goblet cells and the other with prominent foveolar-type cells. Nuclei ranged from deceptively bland to highly atypical. Surface implants were identified in 2 cases. Two ovarian tumors examined expressed cytokeratin 7 and 20 but not estrogen receptor. Three patients with follow-up information all died within 1 year of the ovarian metastases. Although information is limited, our results suggest that metastatic spread to the ovary by intestinal-type gastric adenocarcinoma is usually seen in patients older than those with Krukenberg tumors, with a known history of gastric carcinoma, and with concomitant widespread disease. Involvement of the ovary by intestinal-type gastric carcinoma produces a microscopic picture distinctly different from that of a Krukenberg tumor. These metastatic intestinal-type tumors may be confused with metastases from other gastrointestinal sites that are more frequently the cause of pseudoendometrioid or mucinous metastases, and like such tumors may be confused with primary ovarian endometrioid and mucinous neoplasms.

Adenocarcinoma↗
PubMed2006

Krukenberg tumor of renal pelvic origin: report of a case with selected comments on ovarian tumors metastatic from the urinary tract.

Metastatic tumors to the ovary are infrequently of urinary tract origin. In approximate descending order of frequency, this subset of secondary ovarian neoplasms includes renal cell carcinoma, transitional cell carcinoma of the urinary bladder, and urachal adenocarcinomas. These tumors usually raise a differential in turn of primary ovarian clear cell, transitional cell, or mucinous carcinomas. Only rare metastatic signet-ring adenocarcinomas of the bladder have shown the features of a Krukenberg tumor. We report the case of a 74-year old woman with bilateral Krukenberg tumors metastatic from a primary renal pelvic transitional cell carcinoma with glandular and signet-ring cell differentiation. This unique case reinforces that tumors with signet-ring cell morphology have a propensity to metastasize to the ovary, and indicates that renal pelvic carcinoma rarely may be the source of Krukenberg tumors.

Aged↗
PubMed2006

Primary malignant melanoma of the ovary: a report of 9 definite or probable cases with emphasis on their morphologic diversity and mimicry of other primary and secondary ovarian neoplasms.

Most malignant melanomas encountered in the ovary are metastatic, and the recent literature has focused on such neoplasms. Primary tumors are rare with most reports being only of single cases. When the tumor is associated with teratomatous elements from which it arises, not only is the diagnosis of melanoma much more likely to be made but also is a primary nature proven. However, although all the primary tumors likely are of teratomatous origin, evidence of such an origin may be effaced resulting in problems both in identifying the tumor as melanoma and in determining if it is primary or not. In this report, we describe 9 primary or probably primary ovarian melanomas and explore the varied problems the cases posed. The patients ranged from 18 to 72 years. The tumors, all of which were unilateral, ranged from 4 to 23 cm; only 2 were black. In 6 cases, there was an associated dermoid cyst or monodermal teratoma (struma ovarii), 5 in the ipsilateral and 1 in the contralateral ovary. The tumors were variously composed of large epithelioid cells with eosinophilic cytoplasm, small cells, spindle-shaped cells, or a combination, and in 5 cases, melanin pigment (Masson Fontana positive) was identified. In all cases, most of the tumor cells had prominent nucleoli. All neoplasms had a predominantly diffuse growth pattern with a focal nested architecture in 3 cases. Other noteworthy morphological features were tumor giant cells with wreath-like nuclei (4 cases), signet ring cells (1 case), clear cells (1 case), intranuclear pseudoinclusions (2 cases), a focally myxoid stroma (2 cases), a pseudopapillary appearance caused by degeneration (2 cases), and follicle-like structures (3 cases). In 1 case in a 21-year-old, there was associated hypercalcemia, and focally, the neoplasm, which contained follicle-like structures, resembled small cell carcinoma of the hypercalcemic type. All cases tested by immunohistochemistry were positive with 1 or more melanocytic markers, and electron microscopy performed in 3 cases revealed intracytoplasmic melanosomes or premelanosomes. The wide differential potentially includes neoplasms within most of the categories of primary ovarian neoplasia, as well as metastatic melanoma, and is facilitated by thorough sampling to identify teratomatous elements, by awareness of the spectrum of melanoma in the ovary, and by positivity with melanocytic markers. This is an area where electron microscopy can still also contribute useful information.

Adolescent↗
PubMed2005

Placental site trophoblastic tumor: A study of 55 cases and review of the literature emphasizing factors of prognostic significance.

OBJECTIVE: The placental site trophoblastic tumor is a rare form of gestational trophoblastic disease. Fifteen percent of reported cases have been fatal, but predicting behavior in individual patients has been challenging. METHODS: The clinical, gross and histopathological features of 55 cases and 180 cases in the literature were analyzed for their effect on survival and in relation to tumor stage. RESULTS: The 55 patients in our series were 20 to 62 (average 32) years of age. The tumors occurred on an average of 34 months after the last known gestation. 84% were stage I, 2% stage II, 5% stage III, and 9% stage IV. Serum levels of human chorionic gonadotropin (hCG) were elevated (average 691 mIU/ml) in 77% of the cases. The tumors were on average 5 cm in greatest dimension and were composed microscopically of infiltrative sheets of intermediate (extravillous) trophoblastic cells. The mitotic rate ranged from 0 to 20 (average 5.0) per 10 high power fields. The follow-up interval averaged 4.6 years. Eight patients (15%) died from metastatic tumor, and nine additional patients had metastases or a recurrence but were alive at last contact. The most common metastatic sites were the lungs, liver, and vagina. CONCLUSIONS: Significant factors associated with adverse survival in the present series were age over 35 years (P = 0.025), interval since the last pregnancy of over 2 years (P = 0.014), deep myometrial invasion (P = 0.006), stage III or IV (P < 0.0005), maximum hCG level > 1000 mIU/ml (P = 0.034), extensive coagulative necrosis (P = 0.024), high mitotic rate (P = 0.005), and the presence of cells with clear cytoplasm (P < 0.0005). Only stage and clear cytoplasm were independent predictors of overall survival, while stage and age were the only independent predictors of time to recurrence or disease-free survival. In the literature, factors associated with survival were stage (P < 0.005), interval from preceding pregnancy of over 2 years (P = 0.029), previous term pregnancy (P = 0.046), high mitotic rate (P < 0.0005), and high hCG level (P = 0.037).

Adult↗
PubMed2005

Use of novel immunohistochemical markers expressed in colonic adenocarcinoma to distinguish primary ovarian tumors from metastatic colorectal carcinoma.

Distinguishing primary ovarian carcinoma, particularly endometrioid and mucinous subtypes, from metastatic colorectal carcinoma to the ovary is often difficult on histologic examination alone. Recently, three immunohistochemical markers CDX2, a homeobox gene encoding an intestine-specific transcription factor; alpha-methylacyl-CoA racemase (AMACR/P504S), a mitochondrial and peroxisomal enzyme with fairly restricted expression in selective tumors and beta-catenin, an adenomatous polyposis coli (APC) mutation product resulting in activation of the Wnt pathway, have been reported to have specific and sensitive expression in colorectal carcinomas. We evaluated a panel consisting of antibodies to CDX2, beta-catenin and P504S in 23 primary ovarian adenocarcinomas (13 mucinous and 10 endometrioid) and compared the findings to 22 metastatic colorectal adenocarcinomas (seven mucinous and 15 nonmucinous tumors with endometrioid-like morphology hereafter referred to as pseudo-endometrioid) to the ovary stained with the same panel. Twenty (91%) metastatic tumors expressed at least two markers and seven (32%) expressed all three. In contrast, only three (13%) primary ovarian tumors expressed at least two markers and none expressed all three. Strong (2+, 3+) and diffuse (>40%) expression for CDX2 was noted in 21 (95%) metastatic tumors and five (22%) primary ovarian tumors (three mucinous, two endometrioid). P504S was similarly expressed in seven (32%) metastatic and none of the primary ovarian carcinomas. Nuclear expression of beta-catenin was noted in 13 (59%) metastatic tumors and in eight cases (36%), it was diffuse and strong. In contrast, four (19%) primary tumors showed nuclear expression of this protein with only one (5%) case expressing it in a diffuse pattern. Immunohistochemical expression of gene products and enzymes of colorectal carcinogenesis in some primary ovarian carcinomas suggest that the morphologic similarities between colorectal and mucinous/endometrioid carcinoma of the ovary extends to the genetic level, although differences in the level of expression exist between these tumors. Diffuse expression of all three markers (CDX2, beta-catenin and P504S) in a tumor in the ovary was found to be virtually diagnostic of metastasis from a colorectal primary in this study.

Adenocarcinoma↗
PubMed2005

A brief history of the pathology of the gonads.

Our understanding of gonadal pathology has reached its current state as a result of the contributions of numerous outstanding investigators. Knowledge of testicular tumor pathology dates back to the great British workers Percival Pott and Sir Astley Cooper but the single greatest early stride was made with the description in 1906 by the French urologist Maurice Chevassu of the seminoma. The seminal 1946 paper of Nathan B Friedman and Robert A Moore, which segregated out as a distinct entity embryonal carcinoma, is, however, the foundation for the current classification of testicular tumors. In that year Pierre Masson described the distinctive neoplasm, the spermatocytic seminoma. The 1950s saw the publication of an important paper by Frank J Dixon and Dr Moore and they also wrote the first series fascicle on testicular tumors. In this same timeframe, and thereafter, Robert E Scully made significant contributions to testicular pathology, writing the first English language paper on spermatocytic seminoma, describing several subtypes of sex cord tumor, and also the distinctive lesion of intersex, the gonadoblastoma, as well as playing a major role in 1980 in formulating the current classification of premalignant lesions of the testis. The current classification of testicular tumors was arrived at in the early 1970s when the World Health Organization, under the leadership of Dr FK Mostofi, who himself made notable contributions to testicular pathology, devised what is fundamentally the current classification of neoplasms of the male gonad. Although comments on ovarian pathology were made by such legendary figures of earlier times as Giovanni Battista Morgagni and Matthew Baillie, it is only in the mid to later years of the 19th century that contributions, mostly in Europe, began to move knowledge of ovarian pathology to its current state. Thomas Hodgkin, Richard Bright, and Sir James Paget all wrote extensively on ovarian neoplasms. In 1870, Heinrich Waldeyer, and later in that century, another German, Hermann Johannes Pfannenstiel wrote important papers on the surface epithelial tumors. The latter was likely the first to refer to neoplasms now known as of 'borderline malignancy' and also wrote on pseudomyxoma peritonei and other topics. Their work was followed by that of Robert Meyer who made monumental contributions to gynecological pathology, including recognizing the Brenner tumor as a distinctive neoplasm and proposing the first classification of Sertoli-Leydig cell tumors (arrhenoblastomas). He also coined the term 'disgerminoma' (soon changed to dysgerminoma) for the ovarian tumor that had been described in detail by the French investigator Marcel Chenot 5 years after Chevassu had mentioned the tumor in his paper describing the seminoma. During the Meyer era other significant contributions were made by, among others, Howard C Taylor writing on the borderline tumors and John A Sampson writing on endometriosis and tumors, associated with it. In the second-half of the 20th century major contributions were made by Gunnar Teilum of Denmark and Lars Santesson of Sweden. Dr Teilum delineated the morphologic features of the yolk sac tumor and noted the resemblance of papillary formations within it to the endodermal sinuses of the rat placenta. He also wrote extensively on sex cord tumors in both gonads. At a FIGO meeting in 1961 Dr Santesson played a major role in formulating the first organized classification of the surface epithelial-stromal tumors of the ovary and also promoted the endometrioid carcinoma as a special variant of ovarian cancer. In a career spanning over 50 years, Dr Scully was the architect of the modern classification of ovarian tumors being the driving force behind the influential 1973 World Health Organization classification of them. His many original observations have touched upon virtually all categories of ovarian tumor pathology. His second series fascicle 'Tumors of the Ovaries and Maldeveloped Gonads' utilized the WHO classification and presented a lucid elaboration of his by then vast experience with ovarian tumors. All the above have left a rich legacy which those who follow in their path will be challenged to equal.

Europe↗
PubMed2005

Sex cord-stromal tumors of the ovary and testis: their similarities and differences with consideration of selected problems.

Gonadal sex cord-stromal tumors contain some of the most morphologically interesting neoplasms of the gonads and these lead to many important issues in differential diagnosis. The pathology of these tumors is reviewed with emphasis on new information, similarities and differences in the two gonads, and diagnostic problems. Sertoli cell tumors occur in both gonads being more common in the testis where they usually exhibit a lobular pattern of hollow or solid tubules. In the ovary, tubular differentiation is usually the predominant feature but the lobulation typically seen in the testis is generally not as striking. One variant of Sertoli cell tumor, the large cell calcifying form, appears to be restricted to the male gonad and in contrast to other sex cord tumors is much more frequently bilateral and is associated in many cases with unusual clinical manifestations. In both sexes, patients with Peutz-Jeghers syndrome often have distinctive gonadal pathology. In females, it is in the form of the sex cord with annular tubules whereas in males, the lesion has features that are often intermediate between those of a sex cord tumor with annular tubules and a large cell calcifying Sertoli cell tumor. Sertoli-Leydig cell tumors are more morphologically diverse than pure Sertoli cell tumors and for practical purposes are an issue only in ovarian pathology being exceptionally rare in the testis. The classification proposed by Meyer into well, intermediate, and poor differentiation, remains important prognostically. More recently, heterologous and retiform differentiation has been described. Heterologous tumors most often contain mucinous epithelium, sometimes with small foci of carcinoid or less commonly, and generally in poorly differentiated neoplasms, rhabdomyosarcoma or fetal-type cartilage. Such tumors should be distinguished from pure sarcomas and teratomas. The retiform neoplasms, which tend to occur in young females, may mimic serous borderline tumors or even serous carcinomas. Granulosa cell tumors are much more common in females and in both gonads are divided into adult and juvenile forms. In females, granulosa cell tumors and other sex cord tumors may have markedly bizarre nuclei potentially leading to overdiagnosis as more malignant neoplasms. The juvenile granulosa cell tumor of the testis tends to occur in the first 6 months of life and should be carefully distinguished from the yolk sac tumor of the testis, which usually occurs in a slightly older age group. Occasional sex cord-stromal tumors cannot be readily categorized into the Sertoli or granulosa families and are diagnosed as sex cord-stromal tumors unclassified. In females, this is a relatively common placement for a neoplasm in a pregnant patient. Unclassified tumors are overall more common in males and may entrap residual normal germ cells potentially leading to the erroneous placement of the tumor in the category of a mixed germ cell sex cord-stromal tumor. From the practical viewpoint, the most helpful immunohistochemical findings are the negative staining of sex cord tumors for epithelial membrane antigen, and positive staining for inhibin and calretinin, findings that are converse to those seen in endometrioid carcinomas of the ovary, which commonly have formations that simulate sex cord tumors.

Diagnosis, Differential↗
PubMed2005

Immunohistochemistry as a diagnostic aid in the evaluation of ovarian tumors.

Aspects of immunohistochemistry (IHC), which are useful in the diagnosis of ovarian tumors (mostly neoplasms but also a few tumor-like lesions), are discussed. The topic is first approached by considering the different growth patterns and cell types that may be encountered. Then a few other specific situations in which IHC may assist are reviewed. Selected findings largely, or only, of academic interest are also mentioned. One of the most common situations in which IHC may aid is in the evaluation of tumors with follicles or other patterns which bring a sex cord-stromal tumor into the differential. The distinction between a sex cord tumor and an endometrioid carcinoma with sex-cord-like patterns may be greatly aided by the triad of epithelial membrane antigen (EMA), inhibin, and calretinin, the latter two being typically positive and EMA negative in sex cord tumors, the converse being typical of endometrioid carcinoma. It should be emphasized that granulosa cell tumors may be inhibin negative and, albeit less specific, calretinin is more reliable in evaluating this particular issue. Lack of staining for inhibin and calretinin may also be supportive in leading to consideration of diverse other neoplasms that may form follicles, including metastatic tumors as varied as carcinoid and melanoma. The well-known staining of the latter neoplasm for S-100 protein and HMB-45 may be very helpful in evaluating melanomas with follicular or other unusual patterns, a challenging aspect of ovarian tumor interpretation. The most common monodermal teratoma, struma ovarii, usually has an overt follicular pattern and is easily recognized, but recognition of unusual appearances ranging from oxyphilic to clear cell to various patterns of malignant struma may be greatly aided by a thyroglobulin or TTF 1 stain. IHC for neuroendocrine markers may assist in the diagnosis of primary and metastatic carcinoid tumor. The broad differential diagnosis of glandular neoplasms with an endometrioid-pseudoendometrioid morphology, or mucinous cell type, has been the subject of much exploration in recent years, particularly the distinction between primary and metastatic neoplasms. The well-known CK7 positive, CK20 negative phenotype of primary endometrioid carcinoma, and the converse profile in most metastatic large intestinal adenocarcinomas with a pseudoendometrioid morphology, has been much publicized but albeit an appropriate supportive adjunct in many cases, exceptions from the typical staining pattern may be encountered. It is even less helpful in the case of primary versus metastatic mucinous neoplasia. Evaluation of the expression of mucin gene products has shown mixed, essentially unreliable, results. Experience with other new markers, such as CDX-2, villin, beta catenin, and P504S (racemase), is limited but is in aggregate promising with regard to providing some aid in this area. The rare differential of metastatic cervical adenocarcinoma versus primary ovarian mucinous or endometrioid carcinoma may be aided by strong p16 staining of the former. Staining for alpha-fetoprotein may aid in confirming the diagnosis of endometrioid-like (and hepatoid) variants of yolk sac tumor. Ependymoma of the ovary may also have an endometrioid-like glandular pattern, but positive stains for glial fibrillary acidic protein contrast with the negative results in others neoplasms with a similar pattern. Immunostains may be very helpful in the evaluation of oxyphilic tumors and tumor-like lesions and in some unusual forms of clear cell neoplasia, such as clear cell struma, both subjects being reviewed herein. Immunostains may highlight both the presence and extent of epithelial cells in a variety of circumstances, including microinvasive foci in cases of serous borderline tumors and mucinous carcinomas, and in determining the extent of carcinoma cells and reactive cells within mural nodules of mucinous neoplasms. As in tumor pathology in general, various markers may be crucial in the diagnosis of small round cell tumors of the ovary, and familiar markers of epithelial, lymphoid, leukemic, and melanocytic neoplasms may assist in the analysis of high grade tumors with a poorly differentiated carcinoma, lymphoma-granulocytic sarcoma, malignant melanoma differential. The evaluation of ovarian cystic lesions may be aided by thyroglobulin or TTF 1 (cystic struma), glial fibrillary acid protein (ependymal cysts), and inhibin-calretinin (follicle cysts and unilocular granulosa cell tumors). Stains for trophoblast markers may occasionally aid in the evaluation of germ cell tumors, although routine stains should usually suffice; they may be of academic interest in confirming trophoblastic differentiation in some high grade surface epithelial carcinomas.

Biomarkers, Tumor↗
PubMed2005

Sertoli cell tumors of the ovary: a clinicopathologic and immunohistochemical study of 54 cases.

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.

Adolescent↗