Nonvisualized Ovaries on Ultrasound: Correlation With Surgical Pathology.

ABSTRACT: The risk of malignancy in nonvisualized ovaries on pelvic ultrasound is presumed to be close to zero per imaging correlation; the goal of this manuscript is to define the risk of malignancy in nonvisualized ovaries on pelvic ultrasound as defined by surgical pathology. Records for patients with pelvic ultrasound and surgical pathology containing the word "ovary" or "ovaries" performed at our institution between 10/1/2015 and 9/30/2021 were reviewed. Data for ovarian visualization were extracted from the radiology report and correlated with surgical pathology results within each ovary. Eighty-seven ovaries in 71 patients out of 422 ovaries (20.6%) in 215 eligible patients were not visualized on ultrasound. Twenty ovaries were excluded because imaging showed large pelvic mass, and 19 ovaries were excluded because surgical pathology for the ovary of interest was not available. A total of 48 ovaries in 37 patients were nonvisualized and had available surgical pathology. Out of 48 nonvisualized ovaries, 31 were normal on surgical pathology and 17 had abnormalities, with 15 benign lesions (12 of which were ≤1 cm in size). Two ovaries in 1 patient contained malignant lesions; although the ovaries were not visualized on ultrasound, the scan demonstrated peritoneal carcinomatosis. In conclusion, a high proportion of ovaries (20.6%, 87/422) are not visualized on pelvic ultrasound, and surgical pathology reveals ovarian lesions in 35.4% (17/48) of nonvisualized ovaries on pelvic ultrasound, with the majority being subcentimeter benign lesions. In the absence of peritoneal carcinomatosis, nonvisualized ovaries had no malignant lesions.

Whole cervix imaging of collagen, muscle, and cellularity in term and preterm pregnancy.

Cervical softening and dilation are critical for the successful term delivery of a fetus, with premature changes associated with preterm birth. Traditional clinical measures like transvaginal ultrasound and Bishop scores fall short in predicting preterm births and elucidating the cervix's complex microstructural changes. Here, we introduce a magnetic resonance diffusion basis spectrum imaging (DBSI) technique for non-invasive, comprehensive imaging of cervical cellularity, collagen, and muscle fibers. This method is validated through ex vivo DBSI and histological analyses of specimens from total hysterectomies. Subsequently, retrospective in vivo DBSI analysis at 32 weeks of gestation in ten term deliveries and seven preterm deliveries with inflammation-related conditions shows distinct microstructural differences between the groups, alongside significant correlations with delivery timing. These results highlight DBSI's potential to improve understanding of premature cervical remodeling and aid in the evaluation of therapeutic interventions for at-risk pregnancies. Future studies will further assess DBSI's clinical applicability.

COL1A1::PDGFB fusion-associated uterine sarcoma and response to Imatinib: A case report.

Uterine sarcomas are rare neoplasms of the uterus, some of which are associated with distinctive gene fusions. COL1A1::PDGFB fusion uterine sarcoma is a recently described entity that shares the same genetic alteration as dermatofibrosarcoma protuberans. These uterine sarcomas have a nonspecific spindle cell sarcoma appearance and are CD34 positive by immunohistochemistry. Accurate diagnosis relies on identification of the characteristic fusion by molecular genetic methods. The importance of diagnosing this entity lies in its potential response to targeted therapy with imatinib, a tyrosine kinase inhibitor successfully used in dermatofibrosarcoma protuberans, but only one prior case of COL1A1::PDGFB fusion uterine sarcoma treated with imatinib has been reported. Here, we describe a case of COL1A1::PDGFB fusion uterine sarcoma with response to imatinib after recurrence, with a brief review of this rare tumor.

Metastatic Cholangiocarcinoma to the Uterus Morphologically Imitating Primary Intestinal-type Endometrioid Adenocarcinoma.

Cholangiocarcinoma is an uncommon and aggressive malignancy of intrahepatic and extrahepatic bile ducts. We present a case of a 37-year-old woman with cholangiocarcinoma metastatic to the endometrium that mimicked a primary endometrial adenocarcinoma at resection. The patient is status-post orthotopic liver transplant for cholangiocarcinoma. She presented for evaluation of a clear, odorless vaginal discharge of 6 months' duration. Endometrial biopsy demonstrated an adenocarcinoma with mucinous features similar to primary endometrial adenocarcinoma, but with an immunophenotype consistent with metastatic cholangiocarcinoma. Subsequent hysterectomy demonstrated complete replacement of the native endometrium, a presentation that represents, to our knowledge, the first such reported in the literature. Overall, extragenital metastatic disease to the uterine corpus is rare and involvement of the endometrium even less common. Metastatic cholangiocarcinoma represents a small subset of these metastases to the uterus.

Vascular Malformation and CAP Polyposis: A New Insight into Pathophysiology or Fortuitous Association?

INTRODUCTION: CAP polyposis is a benign colorectal process presenting with multiple colorectal polyps with a "CAP" of inflammatory granulation tissue whose etiology has remained largely unknown. CASE: A 24-year-old male presented with a long-standing history of repeated multiple sessile colonic polyps over a period of 17 years. RESULTS: The numerous polyps showed consistent histologic features of superficial erosion with a surface "CAP" of granulation tissue with minimal submucosa to evaluate over this period. A left hemicolectomy disclosed an extensive vascular malformation. CONCLUSION: The underlying vascular malformation may have an etiologic correlation to the overlying CAP polyps in this patient. Future cases may benefit from an evaluation of the underlying submucosa for the presence of possible vascular malformation likely to be missed on superficial polypectomy.

Phosphomannose Isomerase High Expression Associated with Better Prognosis in Pancreatic Ductal Adenocarcinoma.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death in the United States. The need for increased patient survival has not been met for PDAC. The addition of mannose to conventional chemotherapy leads to accumulation of mannose metabolite in cancer cells and increases subsequent cell death. This susceptibility to mannose depends on the levels of phosphomannose isomerase (PMI). The cancer cells with lower levels of PMI are more sensitive to mannose than cells with higher levels. In this study, we investigated the association of PMI expression with clinical and pathological features of PDAC cases. METHODS: PMI antibody immunohistochemistry (AbCam) was performed on tissue microarrays from 235 PDAC by a standard protocol on Ventana automated immunostainer. The PMI intensity was graded (0-3) and the proportion of positivity was scored. Correlation of PMI expression with staging and survival was analyzed. RESULTS: Of the 235 cases, 51.5% (n=121) cases demonstrated grade 2 intensity with 90.1% of these (n=109) showing positivity in ≥70% of tumor cells. Ninety-eight (41.7%) cases exhibited grade 3 intensity with 94.9% (n=93) of these cases showing ≥70% reactivity. Sixteen cases (6.8%) were nonreactive (intensity grade 0-1). Intensity of PMI expression was associated with significantly better prognosis as assessed by median survival in months (M): grade 0-1 intensity group: 11.2 M; grade 2 intensity group: 25.2 M; and grade 3 intensity group: 33.2 M (p=0.03). A minority (6.8%) of PDACs show non-high PMI expression with poorer prognosis. DISCUSSION: Mannose may be a particularly useful adjunct with chemotherapy to treat this aggressive subgroup. PMI expression is also a potential biomarker to predict the prognosis of PDAC.

Semiquantitative assessment of cytomorphologic features can predict mutation status of thyroid nodules with indeterminate cytologic diagnosis.

Molecular diagnostics increasingly direct the management of thyroid nodules with an indeterminate cytologic diagnosis. This study was undertaken to correlate cytomorphologic features with the molecular profiles in an effort to identify features predictive of molecular aberrations. One hundred eighty-nine thyroid nodules with an indeterminate thyroid cytology diagnosis (atypia of undetermined significance, suspicious for follicular lesion, and suspicious for malignancy) with an adequate sample submitted for targeted mutation detection by polymerase chain reaction or next-generation sequencing were assessed semiquantitatively for the following cytomorphologic parameters: cellularity, Hurthle cell changes, microfollicles, nuclear elongation, nuclear grooves, nuclear enlargement, nuclear atypia, extent of atypia, and colloid. Based on this evaluation, a cumulative cytomorphologic score (CCS) and a more simplified overall atypia score (OAS) were assigned to each case. Associations among mutational status and each of the aforementioned parameters, CCS, and OAS were determined. Of the 189 nodules with indeterminate cytology, 63 (33.3%) harbored at least 1 mutation. RAS and BRAF were the most common mutations, found in 34 (18.0%) and 13 (6.9%) cases, respectively. Both CCS and OAS were highly associated with the presence of all mutations (P < .0001) and with the presence of BRAF and RAS mutations in particular (all P < .01). Semiquantitative assessment of various cytomorphologic features in indeterminate thyroid cytology cases showed a strong association of higher OAS and CCS and incidence of BRAF and RAS mutations. Using a more objective approach to thyroid cytology can potentially decrease the overall number of indeterminate diagnoses, leading to fewer repeat procedures and unnecessary surgical procedures.

Streptococcus pneumoniae - An Uncommon but Noteworthy Cause of Intrauterine Fetal Demise and Acute Necrotizing Funisitis.

Background: Streptococcus pneumoniae (S. pneumoniae) is an uncommon cause of amniotic fluid infection and intrauterine fetal demise. Case report: A 39-year-old G8P2052 presented with preterm premature rupture of membrane at 22 weeks gestation and had a spontaneous vaginal delivery of a neonate who soon expired. Placental examination revealed retroplacental hematoma, acute necrotizing chorioamnionitis, acute three-vessel vasculitis and necrotizing funisitis of the umbilical cord. Postmortem examination demonstrated features of amniotic fluid infection syndrome with blood culture growing S. pneumoniae. Antenatal screening does not typically quantify S. pneumoniae infection, but small series have found vaginal colonization in fewer than 1% of women. Intrauterine or peritoneal infection derives primarily from ascending infection although other routes are hypothetically possible. Intra-amniotic and neonatal infections by S. pneumoniae are associated with high morbidity and mortality. Conclusion: S. pneumoniae should be considered in perinatal death of immature fetus with severe amniotic fluid infection syndrome and acute necrotizing funisitis.

Transvaginal fast-scanning optical-resolution photoacoustic endoscopy.

Photoacoustic endoscopy offers in vivo examination of the visceral tissue using endogenous contrast, but its typical B-scan rate is ∼10 Hz, restricted by the speed of the scanning unit and the laser pulse repetition rate. Here, we present a transvaginal fast-scanning optical-resolution photoacoustic endoscope with a 250-Hz B-scan rate over a 3-mm scanning range. Using this modality, we not only illustrated the morphological differences of vasculatures among the human ectocervix, uterine body, and sublingual mucosa but also showed the longitudinal and cross-sectional differences of cervical vasculatures in pregnant women. This technology is promising for screening the visceral pathological changes associated with angiogenesis.

p16 Immunohistochemistry Is Not Always Required For Accurate Diagnosis of Grade 2 Squamous Intraepithelial Lesions.

OBJECTIVES: Preinvasive squamous neoplasms of the lower genital tract are currently classified using a two-tier system (high- or low-grade squamous intraepithelial lesion) as directed by the Lower Anogenital Squamous Terminology (LAST) guidelines but may also be subclassified as intraepithelial neoplasia grade 1 (-IN1), -IN2, or -IN3. The LAST recommended that all diagnoses of -IN2 be supported by immunohistochemistry (IHC) for p16. We examined whether p16 and Ki-67 IHC are necessary to diagnose -IN2 when the lesion has obvious high-grade histology. MATERIALS AND METHODS: p16 and Ki-67 IHC were performed prospectively and retrospectively on vulvar, vaginal, and cervical specimens with an initial diagnosis of -IN2 based on hematoxylin and eosin morphology, and a final diagnosis was made after consensus review. RESULTS: Five of 46 prospective and four of 38 retrospective cases were p16 negative. The diagnosis of -IN2 was maintained in eight of these nine cases because of compelling high-grade squamous intraepithelial lesion histology. Overall, p16 and Ki-67 IHC altered the -IN2 diagnosis to a lower grade in only one of 84 cases (1.2%, <0.01%-7.1%). Moreover, p16 was positive in all cases where the preanalytic impression was of -IN2/3 (13/13). CONCLUSIONS: p16 IHC lacks utility in cases of morphologically obvious -IN2, because the stain is positive in most cases. The LAST recommendation to use p16 IHC to support all diagnoses of -IN2 will result in performing the immunostain in many circumstances where it is not medically necessary. Among cases that are p16 negative, many have compelling high-grade morphology. The LAST perspective that the stain trumps histology may allow false-negative IHC results to prevail.

Decidual granulomatous reaction in a placenta from a preeclamptic pregnancy: a case report and review of the literature.

We report a case of decidual perivascular non-necrotizing granulomas in a placenta from a pregnancy complicated by severe preeclampsia with no evidence of infection. The mother was a 20-year-old primigravida with severe preeclampsia diagnosed in the third trimester with subsequent delivery of a healthy baby boy at 37 weeks 5 days gestation. Pathologic examination of the placenta showed scattered non-necrotizing granulomas in decidua, often adjacent to remodeled decidual arteries without fibrinoid necrosis. These were well-formed, non-necrotizing granulomas with scant lymphoid cuffs. Polarization microscopy did not show foreign material. There were no histopathologic or clinical findings suggestive of maternal-fetal infection or systemic vasculitis at the time of delivery, and the mother had no other reported conditions associated with granulomatous inflammation. Our case demonstrates that granulomatous reaction may be seen in the placenta from a pregnancy complicated by severe preeclampsia, although work-up for infection may be indicated.

Is vacuolization in amniocytes really pathognomonic for fetal gastroschisis?

Cytoplasmic vacuolization in amniocytes reportedly is specific to gastroschisis, but documentation is anecdotal. To test this point, we compared 47 placentas from documented cases of gastroschisis to 48 placentas from patients without gastroschisis. We found amniocyte vacuolization is highly sensitive (0.94), but not nearly as specific (0.44) for gastroschisis even after accounting for extent or prominence of vacuoles (specificities <0.73). The lack of specificity results from similar, if not identical, cytoplasmic vacuolization seen in term placentas. If one limits comparison to cases delivered before 37 weeks' gestation, then amniocyte vacuolization is highly sensitive (0.95) and specific (0.82) for gastroschisis.

Intratumoral Vasculopathy in Leiomyoma Treated With Tranexamic Acid.

Although intravascular thrombi and infarct-type necrosis have been reported in leiomyomas following tranexamic acid therapy, intratumoral vasculopathy resembling acute atherosis has not been reported to date in patients without exposure to gonadotropin receptor agonist. We describe a case of intratumoral vasculopathy resembling acute atherosis in a leiomyoma in a 49-year-old woman, with hereditary hemorrhagic telangiectasia and menorrhagia, treated with tranexamic acid. The patient had no exposure to gonadotropin receptor agonists. Pathologic examination of the hysterectomy specimen showed a 5.7-cm submucosal leiomyoma containing multiple arteries with fibrinoid change accompanied with abundant subintimal foamy macrophages and occasional luminal thrombi. The vascular media showed scant lymphocytic inflammation without necrosis. The leiomyoma contained numerous mast cells and edematous areas. Vessels outside of the leiomyoma showed neither fibrinoid changes nor inflammation. The patient is alive and well with no signs of systemic vasculitis. We demonstrate that intratumoral vasculopathy resembling acute atherosis may be seen in leiomyomas from patients taking tranexamic acid and postulate that this change results in vascular thrombosis, tumoral edema, and infarct-type necrosis.

Parenchymal infiltration and lymphoma-associated membranoproliferative pattern of glomerular injury: an unusual presentation of mantle cell lymphoma.

Lymphomatous processes have been shown to involve the kidney by direct and paraneoplastic mechanisms. Direct injury can manifest by effacement of typical parenchymal architecture by the lymphomatous infiltrate, and indirect, paraneoplastic mechanisms have been associated with a variety of glomerular lesions. Mantle cell lymphoma (MCL) has rarely been reported to be associated with both direct infiltration and/ or paraneoplastic glomerular lesions. We describe a patient with rapidly progressive glomerulonephritis whose renal biopsy showed effacement of the renal parenchyma by MCL and a membranoproliferative pattern of glomerular injury. The patient's bone marrow was also involved by MCL, and serology revealed small M-spikes and a positive rheumatoid factor. The clinicopathologic findings were consistent with a membranoproliferative pattern of glomerular injury secondary to MCL with infiltrative destruction of renal parenchyma. This case is unusual in that MCL was diagnosed on renal biopsy, that there was a two-pronged mechanism of renal injury, and that there were two separate monoclonal immunoglobulins elaborated by the lymphoma that could be associated with the glomerular injury. Although it is uncommon to make an initial diagnosis of lymphoma from a renal biopsy, it should be recognized that patients with lymphoma might develop clinically significant renal sequelae secondary to both direct and indirect mechanisms of lymphoma-mediated nephropathy.

Meigs' syndrome: a rare cause of recurrent pleural effusion in scleroderma.

Meigs' syndrome represents a triad of pleural effusion, ascites, and an ovarian tumor, usually benign, occurring together. We describe here a case of Meigs' syndrome in a patient with systemic sclerosis, the first such report to our knowledge, in systemic sclerosis. A 53-year-old woman with systemic sclerosis presented with recurrent right-sided pleural effusion, which led to symptoms of shortness of breath, chest tightness, and a non-productive cough. Physical examination revealed a palpable, mobile mass in the right lower quadrant, in addition to typical physical features of scleroderma. Thoracentesis yielded exudative pleural fluid with cytology negative for malignancy. Pleural biopsy was consistent with inflammatory changes, but negative for malignancy. CT scan of the chest, abdomen, and pelvis revealed a soft tissue mass in the pelvis, which appeared to arise from the left ovary. The patient's cancer antigen 125 (CA-125) level was elevated at 222 U/mL (normal range, 0-30 U/mL). The patient underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy. Histology of the left ovarian mass was consistent with an ovarian fibrothecoma, a benign tumor of the ovary. At her 1-month follow-up appointment, the patient had complete resolution of the right-sided pleural effusion. To date, at 10 months past the initial presentation, she has not had recurrence of pleural effusion. Although rare, Meigs' syndrome should be considered as a possible cause of recurrent serositis in women with rheumatologic diseases. Removal of the ovarian tumor leads to prompt resolution of the serositis.

Presence of a sarcomatous component outside the ovary is an adverse prognostic factor for primary ovarian malignant mixed mesodermal/mullerian tumors: a clinicopathologic study of 47 cases.

Primary ovarian malignant mixed mesodermal tumors are uncommon. There exist few data in the literature on the significance of the sarcomatous component (SC) in these tumors. Here we investigated this aspect in 47 such tumors, with particular interest in whether the presence of SC outside the ovary confers a worse prognosis. We correlated various features of the SC (homologous vs. heterologous, type of heterologous SC, extent/percentage, mitotic count, necrosis, whether or not SC is present outside the ovary) with disease-specific survival (DSS) using the Kaplan-Meier method and log-rank test. We also correlated other clinicopathologic parameters with DSS: age, stage, tumor size, tumor laterality, type of the carcinomatous component (CC), lymph node status, vascular invasion, and degree of surgical debulking. The mean age was 69.0 years (range, 43 to 89 y). The tumor was located in the left and right ovary in 18 and 24 patients, respectively (laterality could not be determined in 5 cases). The mean tumor size was 13.6 cm. Surgical debulking was optimal in 28, suboptimal in 6, and unclear in 13 patients. FIGO stage was I in 1 patient, II in 5 patients, III in 40 (IIIA in 1, IIIB in 11, IIIC in 28), and IV in 1 patient. Node metastasis and vascular invasion were noted in 6/17 and 29/47 patients, respectively. The mean percentage of SC was 29% (median 20%; range, 1% to 90%). The SC was heterologous in 34 (72%) and homologous in 13 (28%) patients. The mitotic figures per 10 HPF in SC were 33 (0 to 128). Tumor necrosis was present in 45/47 cases (mean 10%; range, 1% to 40%, only in CC in 14, only in SC in 2, in both SC and CC in 29). The CC was high-grade serous in 27 patients, endometrioid in 2, mixed high-grade serous and endometrioid in 17, and mixed high-grade serous and clear cell carcinoma in 1 patient. The extraovarian tumor contained only CC in 17 cases, only SC in 1 case, and both SC and CC in 28 cases. The median follow-up was 29 months (range, 1 to 183 mo): 6 patients were lost to follow-up, 3 died postoperatively, 29 died from disease, 2 died from other causes, and 7 were still alive (14 to 183 mo). The DSS rate at 1, 2, and 5 years was 75%, 56%, and 21%, respectively. Presence of SC outside the ovary was a significant adverse prognostic factor (P=0.03), whereas other parameters were not. After adjusting for FIGO stage, presence of SC outside the ovary was still a significant adverse prognosticator for stage III patients (P=0.003), whereas others were not. Therefore, our findings showed that presence of SC outside the ovary was a significant adverse prognostic factor. We advocate listing the specific extraovarian tumor component (SC and/or CC) in the pathology report for primary ovarian malignant mixed mesodermal tumors.

Training in EUS-Guided Fine Needle Aspiration: Safety and Diagnostic Yield of Attending Supervised, Trainee-Directed FNA from the Onset of Training.

Background. The optimal time to initiate hands-on training in endoscopic ultrasound fine needle aspiration (EUS-FNA) is unclear. We studied the feasibility of initiating EUS-FNA training concurrent with EUS training. Methods. Three supervised trainees were instructed on EUS-FNA technique and allowed hands-on exposure from the onset of training. The trainee and attending each performed passes in no particular order. During trainee FNA, the attending provided verbal instruction as needed but no hands-on assistance. A blinded cytopathologist assessed the adequacy (cellularity) and diagnostic yield of individual passes. Primary outcomes compared cellularity and diagnostic yield of attending versus fellow FNA passes. Results. We analyzed 305 FNA sites, including pancreas (51.2%), mediastinal/upper abdominal lymph node (LN) (28.5%) and others (20.3%). The average proportion of fellow passes with AC was similar to attending FNA-pancreas: 70.3 versus 68.8%; LN: 79.0 versus 81.7%; others 65.5 versus 68.7%; P > 0.05); these did not change significantly during the training period. Among cases with confirmed malignancy (n = 179), the sensitivity of EUS-FNA was 78.8% (68.4% fellow-only versus 69.6% attending only). There were no EUS-FNA complications. Conclusions. When initiated at the onset of EUS training, attending-supervised, trainee-directed FNA is safe and has comparable performance characteristics to attending FNA.

Reduced Notch signaling leads to renal cysts and papillary microadenomas.

The formation of proximal nephron segments requires canonical Notch2 signaling, but other functions of Notch signaling during renal development are incompletely understood. Here, we report that proximal tubules forming with reduced Notch signaling, resulting from delayed conditional inactivation of Notch1 and/or Notch2, are prone to cyst formation and tubular epithelial stratification. Conditional inactivation of the DNA binding factor RBP-J, which mediates Notch signaling, also resulted in multiple congenital cysts arising from the proximal tubule. Moreover, a few stratified foci/microadenomas containing hyperproliferative cells, resembling precursors of papillary renal cell carcinoma, formed in these proximal tubules. Epithelial stratification correlated neither with reduced expression of the transcriptional regulator of ciliary proteins TCF2/HNF1beta nor with loss of apical-basal polarity. Instead, Notch signaling helped to restrict the orientation of epithelial mitotic spindles to a plane parallel to the basement membrane during nephron elongation. In the absence of Notch, random spindle orientation may explain the epithelial stratification and cyst formation. Furthermore, post hoc analysis of human class 1 papillary renal cell carcinoma revealed reduced Notch activity in these tumors, resulting from abundant expression of a potent inhibitor of canonical Notch signaling, KyoT3/FHL1B. In summary, these data suggest that canonical Notch signaling maintains the alignment of cell division in the proximal tubules during nephrogenesis and that perturbations in Notch signaling may lead to cystic renal disease and tumorigenesis.

Malignant struma ovarii: an analysis of 88 cases, including 27 with extraovarian spread.

Struma ovarii that display extraovarian spread or later recurrence is exceedingly rare. Among 88 patients with "malignant" struma ovarii followed for prolonged periods, several features helped to predict the adverse clinical course. Adhesions (graded 2 to 4+), peritoneal fluid (> or =1 L) or ovarian serosal rent were worrisome features, occurring in 74% of 27 biologically malignant tumors but only 10% of 61 clinically benign tumors. The size of the strumal component rather than the overall size of the ovarian teratoma also had some predictive value. Tumors with a strumal component < or =6 cm recurred rarely (7%), whereas 33% of the consult and 88% of the literature cases > or =12 cm were clinically malignant. Except for a papillary pattern or poorly differentiated cancer, no microscopic feature reliably predicted the clinical outcome, including those typically associated with malignancy in primary thyroid tumors. Among the consult cases, 7% with histologic follicular adenomas and 29% with papillary carcinomas were clinically malignant. Unequivocal vascular invasion was rare, precluding assessment of its effect. Optically clear nuclei, when extensive, were useful to diagnose papillary carcinoma, but were present nevertheless in smaller numbers in both macrofollicular and microfollicular adenomas. Eight tumors confined initially to the ovary (stage 1) recurred. Papillary carcinomas recurred earlier (average 4 y) than follicular adenomatous neoplasms (average 11 y, range: 1-29 y). Overall, the survival rate for all patients was 89% at 10 years and 84% at 25 years, indicating the need for routine long-term follow-up.