Ovarian clear cell carcinoma with papillary features: a potential mimic of serous tumor of low malignant potential

The differential diagnostic problems usually associated with clear cell carcinoma (CCC) of the ovary have been well characterized and include primitive germ cell tumor, sex cord stromal tumor, and metastasis. Distinction from other types of surface epithelial carcinoma may also pose a diagnostic challenge, but the potential for misdiagnosis of serous tumor of low malignant potential (S-LMP) is not well recognized. We report 13 cases of ovarian CCC with prominent papillary architecture that were initially misdiagnosed as S-LMP or low-grade serous carcinoma either on frozen section or at final diagnosis. The ages of the patients ranged from 39 to 65 years (mean, 52.2 y). All patients presented with a pelvic mass; 1 was undergoing evaluation for infertility. Macroscopically, most were described as unilateral, multilocular cysts with internal papillary structures. On microscopic examination, each tumor had a papillary architecture that accounted for 30% to 95% of the tumor; in 6 cases, the cores of the papillae were hyalinized. The neoplastic cells covering the papillae had clear to granular and eosinophilic cytoplasm. Hobnail cells were focal and often subtle. Most had a low mitotic index (9/13) and/or deceptively bland cytology (8/13); only careful attention to the cytologic features and/or mitotic index allowed correct identification of the tumor type in 5 cases. Six were associated with pelvic/ovarian endometriosis. Ten were Federation of Gynecology and Obstetrics stage I (8 IA, 2 IC), 2 were stage II (1 IIB, 1 IIC), and 1 stage IIIC. CCC with prominent papillary architecture is uncommon, but may pose a challenging differential diagnosis with S-LMP, resulting in inadequate staging and delayed treatment. Features most helpful in distinguishing papillary CCC are unilaterality, nonhierarchical branching, monomorphous cell population, and the presence of more typical CCC patterns elsewhere in the tumor. The presence of endometriosis, although not specific, should also prompt consideration for papillary CCC. Increased numbers of mitotic figures may not be present and high-grade cytologic atypia may be focal, requiring careful examination of multiple tumor sections for detection. As CCC and S-LMP exhibit significantly different immunoreactivity for Wilms' Tumor 1 and estrogen receptor, these markers may also be useful adjunctive tests in problematic cases.     

Ovarian serous tumors of low malignant potential (serous borderline tumors). The relationship of exophytic surface tumor to peritoneal "implants".

A series of 98 ovarian serous tumors of low malignant potential (LMP) was studied to test the validity of the implantation theory of extraovarian peritoneal spread of tumor by assessing the association between exophytic tumor on the ovarian surface and synchronous peritoneal implants. Patient's ages ranged from 17 to 77 years (mean, 37.8 years). The ovarian tumors were bilateral in 39 cases (40%). Exophytic tumor was present in 47 (48%) cases and involved at least one ovary in 82% of bilateral tumors. Exophytic tumor was found in 29 of 31 patients (94%) with peritoneal implants, but in only 18 of 67 patients (27%) without peritoneal implants. Moreover, 29 of 47 patients (62%) with exophytic tumor had peritoneal implants compared with only 2 of 51 patients (4%) without exophytic tumor. The utility of exophytic tumor as a marker of synchronous peritoneal implants had a diagnostic sensitivity of 94%, a diagnostic specificity of 73%, and an efficiency of 80%. Because of the strongly positive correlation between exophytic tumor and peritoneal implants, the implantation theory remains as a highly likely explanation for extraovarian spread of ovarian serous LMP tumors. The multicentric "field effect" theory, however, cannot be entirely excluded and may be operative in some cases.     

Ovarian serous tumors of low malignant potential (borderline tumors): outcome-based study of 276 patients with long-term (> or =5-year) follow-up

The natural history, classification, and nomenclature of ovarian serous tumors of low malignant potential (S-LMP) (serous tumors of borderline malignancy, atypical proliferating tumors) are controversial. To determine long-term outcome for patients with S-LMP and further evaluate whether S-LMP can be stratified into clinically benign and malignant groups, the clinicopathologic features of 276 patients with S-LMP and > or =5 year follow-up were studied. The histology of the ovarian primary, extraovarian implants, and recurrent tumor(s) were characterized using World Health Organization criteria and correlated with FIGO stage and clinical follow-up. After censoring nontumor deaths, overall survival and disease-free survival for the 276 patients was 95% (98% FIGO stage I; 91% FIGO II-IV) and 78% (87% FIGO stage I; 65% FIGO stage II-IV), respectively. Unresectable disease (P < 0.001) and invasive implants (P < 0.001) were associated with decreased survival. When compared with typical S-LMP, S-LMP with micropapillary features were more strongly associated with invasive implants (P < 0.008) and decreased overall survival (P = 0.004), but patient outcome with micropapillary S-LMP was not independent of implant type. Stromal microinvasion in the primary tumor was also correlated with adverse outcome, independent of stage of disease, micropapillary architecture, and implant type (P = 0.03). There was no association between outcome and lymph node status. Transformation to low-grade serous carcinoma occurred in 6.8% of patients at intervals of 7 to 288 months (58% > or = 60 months) and was strongly associated with increased tempo of disease and decreased survival (P < 0.001). S-LMP forms a heterogeneous group, morphologically and clinically distinct from benign serous tumors and serous carcinoma. The majority of S-LMP are clinically benign, but recurrences are not uncommon, and persistent disease as well as deaths occur. Progression to low-grade serous carcinoma is highly predictive of more aggressive disease. Other features associated with recurrent and/or progressive disease include FIGO stage, invasive implants, microinvasion in the primary tumor, and micropapillary architecture. These predictors tend to co-occur, and no single clinical or pathologic feature or combination of features identify all adverse outcomes. The small, but significant risk of progression over time to low-grade serous carcinoma emphasizes the need for prolonged follow-up in patients with S-LMP.     

Ovarian epithelial tumors of low malignant potential: a case series of 5 adolescent patients

Epithelial ovarian neoplasms are uncommon in pediatric and adolescent patients, accounting for approximately 20% to 30% of ovarian tumors in adolescent females and women younger than 25. Tumors of low malignant potential (LMP) account for a significant proportion of epithelial neoplasms in this patient population. This case series describes 5 adolescent patients, with a mean age of 14.4 ± 2.4 years, diagnosed with ovarian tumors of LMP at one institution.Between November 2001 and January 2006, 5 patients were diagnosed with ovarian tumors of LMP of 126 patients who had surgery for adnexal masses. All patients underwent initial surgery via laparotomy. Two patients underwent ovarian cystectomy, and 3 had at least a unilateral salpingo-oophorectomy. One patient had stage IIIc disease, whereas the other 4 patients, not all completely staged, had presumed stage I disease. Three patients developed recurrent ovarian masses on follow-up. Two had recurrent LMP tumors (one bilateral) and one was a benign mucinous cystadenoma.This case series of 5 adolescent patients with ovarian tumors of LMP highlights the importance of considering epithelial neoplasms in any pediatric or adolescent patient with a pelvic mass and supports conservative management, with staging and fertility-sparing surgery; however, appropriate follow-up is essential, as evidenced by 3 of 5 patients exhibiting recurrent ovarian masses.     

Lymphatic vascular invasion in ovarian serous tumors of low malignant potential with stromal microinvasion: a case control study

Stromal microinvasion in ovarian serous tumors of low malignant potential (S-LMP) stratifies patients at long-term risk for disease progression independent of stage and primary ovarian histology. Despite the histologic impression and often-quoted incidence of lymphatic vascular invasion (LVI) in S-LMP with stromal microinvasion, there has been no formal evaluation in a case control series of S-LMP. The presence and extent of (LVI) was assessed in 20 S-LMP with stromal microinvasion and 20 S-LMP case controls without stromal microinvasion and compared with a series of low-grade and high-grade serous carcinomas using D2-40 monoclonal antibody recognizing podoplanin, a novel lymphatic endothelial marker. S-LMP case controls were matched for primary ovarian histology (usual vs. micropapillary), International Federation of Gynecology and Obstetrics (FIGO) stage, and age (best possible match). The patterns of stromal microinvasion included individual eosinophilic cells and cell clusters, cribriform, simple and noncomplex branching papillae, and inverted macropapillae. Immunohistologic staining with D2-40 monoclonal antibody clearly identified intratumoral LVI in 12/20 (60%) S-LMP with stromal microinvasion and 0/20 S-LMP without stromal microinvasion. Although only 4/13 (31%) low-grade serous carcinomas and 7/20 (35%) high-grade serous carcinomas had intratumoral LVI, hilar LVI was more common in the carcinomas (15% low-grade; 69% high-grade). Intratumoral LVI in S-LMP ranged from focal (6 cases) to multifocal (6 cases, maximum of 5 discrete foci) in any 1 section and included isolated single cells, simple papillae, and in 1 case, cribriform glands. Multifocal LVI was identified in 1 study patient who was pregnant. One of the 12 S-LMP patients with LVI had an intra-abdominal recurrence with high-grade disease at 16 months; whereas all other patients with follow-up were free of disease. LVI in ovarian S-LMP was significantly associated with the presence of stromal microinvasion (P<0.0001) and is independent of age, stage, primary ovarian histology, and pattern or extent of microinvasion. The presence of LVI in microinvasive S-LMP corroborates the view that microinvasion represents an early, but very low risk, invasive process that morphologically links S-LMP and low-grade serous carcinoma.     

Peritoneal serous micropapillomatosis of low malignant potential (serous borderline tumors of the peritoneum). A clinicopathologic study of 17 cases.

Primary peritoneal serous micropapillomatosis of low malignant potential, or serous borderline tumor of the peritoneum, is a relatively rare lesion that is histologically indistinguishable from peritoneal "implants" associated with ovarian papillary serous tumors of low malignant potential. We analyzed 17 cases to further define the pathologic features and prognosis of this entity. The ages of the patients ranged from 16 to 67 years (mean, 33 years). Eight patients were symptomatic with chronic pelvic or abdominal pain (five patients), adnexal mass (one patient), small-bowel obstruction (one patient), and possible endometriosis (one patient). In nine cases (53%), peritoneal serous micropapillomatosis of low malignant potential was an incidental finding discovered during evaluation or treatment of other conditions. Grossly, the peritoneal lesions were focal or diffuse. They commonly appeared as miliary granules and often were believed to be peritoneal carcinomatosis. Microscopically, peritoneal serous micropapillomatosis of low malignant potential had all of the patterns seen in superficial ("noninvasive") peritoneal implants of ovarian serous borderline tumors. Psammoma bodies were a prominent feature of all cases. Twelve patients also had typical endosalpingiosis. Most patients were treated by hysterectomy and bilateral salpingo-oophorectomy. Surgical treatment in seven patients consisted only of biopsy. Ten patients had residual unresected disease at the time of their initial operation. Several patients received adjuvant chemotherapy. Follow-up was available for 14 of the 17 patients. One patient died of metastatic breast carcinoma at 3.8 years; another patient died 7 weeks after operation, possibly as a complication of therapy. The other 12 patients were alive at last known contact after follow-up intervals of 8 months to 16.2 years (mean, 7.5 years). Two of these 12 patients developed multiple episodes of small-bowel obstruction due to persistent peritoneal serous micropapillomatosis of low malignant potential; neither received adjuvant chemo- or radiotherapy. Both were alive without progressive disease 10.9 and 16.2 years after initial diagnosis, respectively. This excellent prognosis supports a regimen of conservative therapy for these patients.     

The development of high-grade serous carcinoma from atypical proliferative (borderline) serous tumors and low-grade micropapillary serous carcinoma: a morphologic and molecular genetic analysis

Recently, we have proposed a model for the development of ovarian surface epithelial tumors. In this model, all histologic types of surface epithelial tumors are divided into 2 categories designated type I and type II which correspond to 2 pathways of tumorigenesis. Type I tumors include low-grade serous carcinoma, mucinous carcinoma, endometrioid carcinoma, malignant Brenner tumor, and clear cell carcinoma which develop slowly in a stepwise fashion from well-recognized precursors, namely atypical proliferative (borderline) tumors. Type II tumors are high-grade, rapidly growing tumors that typically have spread beyond the ovaries at presentation. They include high-grade serous carcinoma ("moderately" and "poorly" differentiated), malignant mixed mesodermal tumors (carcinosarcomas), and undifferentiated carcinoma. These tumors are rarely associated with morphologically recognizable precursor lesions and it has been proposed that they develop "de novo" from ovarian inclusion cysts. This model implies that the pathogenesis of type I and type II tumors are separate and independent but it is not clear whether some type II tumors develop from type I tumors. In this study, we attempted to address this issue by determining the clonality of 6 cases of high-grade serous carcinomas that were closely associated with atypical proliferative serous (borderline) tumors and invasive low-grade micropapillary serous carcinomas. We reviewed 210 ovarian serous tumors from the surgical pathology files of the Johns Hopkins Hospital and identified 3 high-grade serous carcinoma that were directly associated with atypical proliferative serous (borderline) tumors and 3 that were associated with invasive low-grade micropapillary serous carcinomas. A morphologic continuum between the high-grade carcinoma and the low-grade tumors was observed in 4 cases whereas in the remaining 2 cases the high-grade and low-grade components were separate. Mutational analyses for KRAS, BRAF, and p53 genes were performed on microdissected samples from the high-grade and low-grade tumor areas for each case. All 6 tumors demonstrated wild-type BRAF and p53 genes. Only 2 of the 6 cases were informative from a molecular genetic standpoint. In those 2 cases we found the same mutations of KRAS in both the atypical proliferative serous (borderline) tumor and the high-grade serous carcinoma component of the tumor, indicating a clonal relationship. The above results suggest that the majority of high-grade and low-grade carcinomas develop independently but in rare cases, a high-grade serous carcinoma may arise from an atypical proliferative serous (borderline) tumor.     

Ovarian endometrioid tumors of low malignant potential: a clinicopathologic study of 30 cases with comparison to well-differentiated endometrioid adenocarcinoma

Thirty cases of ovarian endometrioid tumor of low malignant potential (ETLMP) were studied and compared with 32 cases of well-differentiated endometrioid adenocarcinoma. ETLMP was distinguished from well-differentiated endometrioid adenocarcinoma by the absence of destructive stromal invasion, glandular confluence, or stromal disappearance. Intraepithelial carcinoma in a low malignant potential tumor was defined as areas showing grade 3 nuclei, sometimes associated with an intracystic villoglandular or cribriform pattern. Microinvasion in an ETLMP was defined as one or more areas of invasion with an area of < or =10 mm2. Because a cribriform pattern may be seen in purely intraglandular proliferations, the latter was not taken as evidence of invasion. The patients with ETLMP ranged from 28 to 86 years of age (mean 54.9 years), and only one patient (3%) had other than stage I disease at presentation. The patients with well-differentiated endometrioid carcinoma ranged from 26 to 87 years of age (mean 51.1 years), and three patients (9%) had stage II disease at presentation. An adenofibromatous pattern was present in 47% of cases of ETLMP and squamous differentiation in 47%; intraepithelial carcinoma occurred in 7% of cases and stromal microinvasion in 7%. None of these findings appeared to influence the prognosis because all patients with ETLMP were free of recurrent disease or metastasis on follow-up, whereas 20% of patients with well-differentiated endometrioid adenocarcinoma followed for >6 months developed recurrent disease. Thus, the prognosis of ETLMP, when defined by the above criteria, is favorable and is superior to that of well-differentiated endometrioid adenocarcinoma.     

Serous tumors involving extra-abdominal/extra-pelvic sites after the diagnosis of an ovarian serous neoplasm of low malignant potential

The involvement of extra-abdominal/extra-pelvic sites by serous tumors after the diagnosis of an ovarian serous neoplasm of low malignant potential is extremely rare. In this study we present the clinicopathologic features of 12 such cases seen at our institution during a period of 19 years (1980-1999). The patients' age ranged from 19 to 50 years (mean 33 years). By FIGO staging the original ovarian tumors were distributed as follows: stage I, 4; stage II, 2; stage III, 5; unknown stage, 1. All patients were treated surgically. Ten patients also received adjuvant therapy (radiotherapy, 2; chemotherapy and radiotherapy, 4; chemotherapy, 3; intraperitoneal 32P, 1). The interval between the diagnosis of the ovarian neoplasm and the subsequent tumor involving an extra-abdominal/extra-pelvic site ranged from 4 to 240 months (mean 124 months). Sites of extra-abdominal/extra-pelvic involvement and the number of cases were as follows: left neck lymph nodes (LNs), 4; left and right neck LNs, 1; pleura, 2; lung, 1; mediastinum, 1; chest wall, 1; axillary and chest LNs, 1; and vertebral body, 1. Eight patients were treated with chemotherapy, 1 with radiotherapy, 2 with chemotherapy and radiotherapy, and 1 with surgery alone. Follow-up ranging from 5 months to 18 years was available in 11 patients. Six patients died of disease and 5 patients were alive with no evidence of disease. In this small series of cases, no definitive clinical or pathologic feature related to the occurrence of extra-abdominal/extra-pelvic serous tumors was found. Based on the LN involvement and the endosalpingiosis seen in some cases, these tumors might develop from circulating neoplastic serous cells or from areas of endosalpingiosis involving extra-abdominal/extra-pelvic sites.     

Histopathological and immunohistochemical study of papillary urothelial neoplasms of low malignant potential and grade associated with extensive invasive low-grade urothelial carcinoma

OBJECTIVE: To report five cases of papillary urothelial neoplasm of low malignant potential (UNLMP) and papillary urothelial carcinoma of low grade (UCLG) associated with extensive muscle invasion, and to investigate the clinical and histopathological presentation and their immunohistochemical properties. MATERIALS AND METHODS: Consecutive cystectomy and correlating transurethral resection (TUR) of urinary bladder tumour specimens were reviewed to identify cases of UCLG having extensive invasion into the urinary bladder wall. All specimens were stained immunohistochemically, as were those from 10 control cases having reactive urothelium or superficial UNLMP. The clinical charts were reviewed. RESULTS: Of a total of 95 cystectomy cases there were four of UNLMP or UCLG with extensive invasion. An additional case was added from our consultation file. All five cases had biopsies misdiagnosed as benign lesions or prostatic adenocarcinoma. The superficial invasive components consisted of UCLG conforming to the previously described entities of nested transitional cell carcinoma (TCC), microcystic or deceptively benign-appearing TCC. Immunostaining for cytokeratin 20, MIB-1 and p53 was similar to reactive epithelia, whereas E-cadherin immunoreactivity was slightly different, with focal negativity compared with extensive immunoreactivity in invasive vs noninvasive UCLG. Four patients developed distant metastases; three died within a follow-up of 3 years. CONCLUSIONS: UNLMP and UCLG that widely and deeply invade the bladder accounted for 4% of urothelial carcinoma (UC) in cystectomy specimens and commonly pose diagnostic problems in superficial TUR specimens. From this study with few cases the diagnosis of this entity in superficial biopsies is aided by an awareness of it and by identifying 'benign appearing' nests of urothelial cells which are deeply seated in the stroma. Immunostaining is unlikely to be very useful.     

Lymph node involvement in ovarian serous tumors of low malignant potential (borderline tumors): pathology, prognosis, and proposed classification

The occurrence of regional lymph node involvement (LNI) in patients with primary ovarian serous tumors of low malignant potential (S-LMP), although well described in the literature, continues to be problematic. Most studies indicate that LNI is not associated with an adverse prognosis, but there has not been a comprehensive study addressing the histologic patterns of LNI, the importance, if any, of classifying the type of LNI (ie, as either noninvasive or invasive in analogy to peritoneal implant classification), or the presence and significance of associated endosalpingiosis. To further evaluate LNI in S-LMP, 74 patients with ovarian S-LMP and a lymph node biopsy or sampling were studied. Thirty-one of 74 patients had LNI in pelvic (18; 58%), mesenteric/omental (9; 29%), paraaortic (8; 26%), or supradiaphragmatic (2; 6%) lymph nodes. The number of involved nodes ranged from 1 to 20 (mean, 11.1). Four patterns of LNI were identified: individual cells, clusters of cells, and simple, nonbranching papillae (28 of 31; 90%); intraglandular (21 of 31; 68%); cells with prominent cytoplasmic eosinophilia ("eosinophilic cell" pattern) (16 of 31; 52%); and micropapillary pattern (5 of 31; 16%). LNI was diffuse in at least one lymph node in 13 patients (42%) and formed nodular aggregates greater than 1 mm in 6 patients (19%). Nodal endosalpingiosis was present in 58% of cases with LNI compared with 35% without LNI (P=0.06). There was no significant difference in survival for patients with LNI compared with patients without LNI. However, the presence of discrete nodular aggregates of epithelium greater than 1 mm in linear dimension without intervening lymphoid tissue was associated with a statistically significant decreased disease-free survival when compared with other patterns of LNI (P=0.02). Nodular aggregates were strongly associated with desmoplastic fibrous stromal reaction (P=0.001) and micropapillary architecture (0.02). There was also a trend for decreased survival among patients with LNI without associated endosalpingiosis (56%) compared with patients with LNI associated with endosalpingiosis (85%) and those with endosalpingiosis only (93%). This study suggests that patients with ovarian S-LMP may be further substratified into risk categories by the presence of nodular aggregates of S-LMP in lymph nodes, a feature that is more common in cases with micropapillary architecture and associated stromal reaction in the intranodal tumor. This high risk pattern of LNI may have a predictive value similar to invasive peritoneal implants and deserves independent evaluation in future studies of S-LMP.     

Micropapillary and cribriform patterns in ovarian serous tumors of low malignant potential: a study of 99 advanced stage cases

Recently some investigators have proposed abandoning the term ovarian serous tumor of low malignant potential (SLMP) and dividing the tumors in this category into two new groups, micropapillary serous carcinoma and atypical proliferative serous tumor, based on the presence or absence of marked epithelial proliferation with a micropapillary or cribriform pattern (MP/CP). We reviewed 99 cases of advanced stage SLMP (FIGO stages II and III) to determine whether the presence or absence of MP/CP predicts the clinical course, thus justifying the proposed change in terminology. Eighteen cases of MP/CP and 81 cases of typical SLMP were identified. The patients with MP/CP ranged from 23 to 59 years of age at the time of diagnosis (median 35 years), whereas those with typical SLMP were 17 to 67 years old (median 38 years). Bilateral ovarian involvement by SLMP was more frequent in the MP/CP cases, 13 of 18 (72%), as compared with the cases with typical SLMP, 46 of 81 (57%). There was a trend toward a greater frequency of invasive implants in MP/CP cases, 3 of 18 (17%) MP/CP versus 5 of 81 (6%) typical. The mean follow-up period was 125 months for MP/CP patients and 132 months for the typical group. Differences in the frequency of recurrence and the progression-free survival between the groups were found to be significant. Fourteen (78%) of the MP/CP patients experienced either progression or recurrence of disease, whereas 25 (31%) of the typical SLMP patients had a recurrence (p = 0.001). The progression-free survival ranged from 3 to 208 months for MP/CP patients versus 15 to 233 months for typical SLMP patients (p <0.0001). The majority of the recurrences in both groups were low-grade serous carcinoma, 11 of 14 (79%) patients with progression/recurrence in the MP/CP group and 17 of 25 (68%) patients with recurrence in the typical group. The overall survival of the patients in the two groups, however, was not significantly different. Five (28%) MP/CP patients and 12 (15%) patients with typical SLMP died of disease (p = 0.11). All 17 of these patients developed serous carcinoma and died secondary to tumor progression. Four of eight (50%) patients with invasive implants and 13 of 91 (14%) patients with noninvasive implants died of disease. Our findings of more frequent bilateral ovarian involvement, more frequent recurrence with a shorter progression-free interval, and the trend toward a more frequent association with invasive implants support the contention that MP/CP SLMP are a distinct subgroup of serous tumors. However, the overall survival of patients with MP/CP SLMP is similar to that of patients with typical SLMP and justifies the retention of tumors with MP/CP within the LMP category. Additionally, our long-term follow-up of patients with typical SLMP indicates that a number of these tumors do not follow a benign course and supports their continued designation as borderline neoplasms.     

Patterns of stromal invasion in ovarian serous tumors of low malignant potential (borderline tumors): a reevaluation of the concept of stromal microinvasion

Stromal-epithelial patterns of invasion in serous tumors of the ovary have been subclassified as destructive and nondestructive. By definition, well-differentiated serous tumors featuring destructive stromal invasion are classified as low-grade serous carcinomas whereas those with either no stromal invasion or stromal microinvasion are classified as serous tumors of low malignant potential (S-LMP). The histologic features of stromal microinvasion in ovarian S-LMP have been addressed in a variety of studies, but controversy persists regarding diagnostic criteria and prognostic significance, particularly in patients with high-stage disease. In addition, a subset of otherwise typical S-LMP has patterns of invasion that are not classic destructive invasion and do not meet the current diagnostic criteria for stromal microinvasion because of either qualitative features or size restrictions. To further evaluate the full histologic spectrum of stromal-epithelial patterns of invasion in otherwise typical S-LMP, we examined a series of 60 ovarian S-LMP (34 FIGO stage I; 26 FIGO stages II, III, and IV) with stromal-epithelial alterations not meeting criteria for classic destructive invasion. This group of cases included those meeting the definition of microinvasion and a subset that would be excluded based on size measurements or unusual qualitative features, but did not exhibit significant stromal reaction. Five patterns of invasion were identified: individual eosinophilic cells and cell clusters, cribriform, simple and noncomplex branching papillae, inverted macropapillae, and micropapillae. Individual, discrete aggregates of invasive epithelium ranged from 1 to 12 mm (mean, 1.4 mm) in greatest linear dimension as measured by conventional methods. The number of discrete foci ranged from 1 to greater than 10; in 7 tumors (12%), the invasive foci were diffusely scattered throughout the stroma without discrete aggregates. These stromal-epithelial alterations were associated with disease progression and/or death due to disease in 9 of 50 (18%) patients with follow-up (mean, 92.5 mo) and were covariant with other adverse prognostic features (invasive implants, nodular lymph node aggregates, high stage, and unresectable disease). Disease progression was most strongly linked to the presence of micropapillae, but the majority of patients with adverse outcome had the more common, classic stromal-epithelial patterns associated with microinvasion (ie, individual cells, cell clusters, and simple papillae). Neither size of the largest contiguous aggregate nor extent of stromal involvement correlated with outcome. Classic microinvasion disproportionately occurred in patients presenting during pregnancy (P<0.0001), and was not associated with adverse outcome in that setting, but follow-up was limited. Based on the cumulative outcome data, the presence of stromal-epithelial patterns of invasion distinct from classic destructive invasion in otherwise typical S-LMP stratifies patients at long-term risk for disease progression, but does not warrant a diagnosis of carcinoma or a change in current management schemes. Maintaining classification as a serous tumor of low malignant potential (serous borderline tumor) with stromal invasion seems appropriate even in the presence of diffuse stromal involvement or discrete aggregates measuring greater than 3 (or 5) mm. As the stromal-epithelial alteration featuring micropapillae may represent a comparatively higher-risk lesion with a clinical course analogous to that of low-grade serous carcinoma, pathologists should identify this specific stromal-epithelial pattern in the diagnostic report until sufficient data is acquired to form more definitive conclusions regarding its prognosis.     

Low-grade ovarian serous neoplasms (low-grade serous carcinoma and serous borderline tumor) associated with high-grade serous carcinoma or undifferentiated carcinoma: report of a series of cases of an unusual phenomenon

Recent literature has suggested a dual pathway of ovarian serous carcinogenesis, with most serous carcinomas falling into 1 of 2 categories, low grade and high grade. These are considered to represent 2 distinct tumor types with a different underlying pathogenesis and associated with different molecular events, clinical behavior, and prognosis. Low-grade serous carcinoma is thought to evolve in many instances from a preexisting serous borderline tumor and cystadenoma. Given the distinct pathogenesis and different molecular events, it is expected that the coexistence of low-grade and high-grade serous carcinoma would be rare or may even be mutually exclusive; moreover, there are very few reported examples in the literature. We report a series of 7 cases in patients aged 34 to 78 years in whom ovarian low-grade serous carcinoma (4 cases, including 3 with associated serous borderline tumor), serous borderline tumor (2 cases), or seromucinous borderline tumor (1 case) was associated with a high-grade carcinoma, either high-grade serous (5 cases) or undifferentiated carcinoma (2 cases). The low-grade and high-grade components coexisted in the original neoplasm in 4 cases, and the high-grade component was present only in recurrence in 3 cases. In both instances, the undifferentiated carcinoma had a focal rhabdoid morphology, and alternative primary sites of tumor were excluded by a combination of clinical, radiologic, and pathologic parameters. We illustrate that low-grade serous carcinoma or serous borderline tumor ("low-grade" serous neoplasms) may rarely be associated with, and probably give rise to, a high-grade carcinoma, either high-grade serous or undifferentiated carcinoma. The coexistence of a low-grade serous neoplasm and undifferentiated carcinoma can be regarded as a form of dedifferentiation. p53 was diffusely positive in 4 of 6 high-grade carcinomas, which raises the possibility that secondary Tp53 mutation is important in high-grade transformation in some of these cases. WT1 was negative in the 2 undifferentiated carcinomas, and PAX8 was positive in 1, suggesting that the latter marker is more useful in helping to confirm a Mullerian origin in dedifferentiated low-grade serous neoplasms.     

Ovarian carcinoma of low malignant potential treated at the Jewish General Hospital, Montreal, between 1973 and 1997.

OBJECTIVE: To review the epidemiologic and pathological characteristics and the management of ovarian cancer of low malignant potential (LMP) at a university teaching institution. DATA SOURCE: Hospital charts from 1973 to 1997. DATA EXTRACTION: The authors carried out a manual study of the individual hospital charts covering the study period. DATA SYNTHESIS: The findings of this review revealed that the mean age of the 30 women in the study was 48.7 years and was similar in the subgroups of women having serous (18) and mucinous (9) types. In those women for whom staging information was available, all had either stage I disease (12 serous, 7 mucinous) or stage III disease (4 serous, 1 mucinous). Treatment consisted of: total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO) with or without omentectomy (OM); BSO, unilateral oophorectomy or ovarian cystectomy alone; or TAH, OM and left salpingo-oophorectomy in women with stage I tumours. All women with stage III tumours underwent TAH, BSO and OM. The recurrence rate was low. Only 1 of 22 stage I tumours but 3 of 5 stage III tumours recurred. CONCLUSIONS: Appropriate postoperative treatment for women with this type of ovarian cancer should be conservative. However, the management of higher stage disease remains controversial.     

Intratesticular serous papillary cystadenoma of low malignant potential: an ultrastructural and immunohistochemical study suggesting müllerian differentiation

A 51-year-old man was found to have two separate intratesticular serous cystadenomas of low malignant potential. Electron microscopy and OC 125 antibody reactivity characterize the neoplasms as serous and suggest müllerian histogenesis.     

Epithelial ovarian tumours of low malignant potential

The available literature and the management of epithelial tumours of low malignant potential (LMP) is reviewed. The criteria for a diagnosis of LMP at the University of the Witwatersrand are delineated in detail. Based on the records in the Ovarian Tumour Registry of this University, experience with 29 such tumours over 4 years is presented. Of these, 14 (48.3%) were of the serous variety, 12 were mucinous (41.4%), and 2 (6.9%) were mucinous-serous, the remaining 1 (3.4%) being endometrioid. LMP tumours accounted for 12.9% of proliferating epithelial ovarian tumours in black patients compared with 16.9% in white patients. Pelviperitoneal cytological washings for detection of malignant cells in patients with LMP tumours is mandatory.     

Endometrioid proliferative and low malignant potential tumors of the ovary. A clinicopathologic study of 46 cases

We evaluated 41 endometroid neoplasms with features intermediate between a benign endometrioid tumor and endometrioid carcinoma. Although these tumors showed various degrees of epithelial proliferation, they lacked the destructive stromal invasion of carcinoma. Intermediate endometrioid tumors were subdivided into proliferative endometrioid tumors (PET), endometrioid tumors of low malignant potential (ETLMP), and ETLMP with microscopic areas of invasion. PET were adenofibromas with solid aggregates of epithelial proliferation not exceeding 5 mm in any dimension, whereas ETLMP either had noninvasive cytologically malignant epithelium or aggregates of atypical epithelium measuring at least 5 mm in any dimension uninterrupted by fibromatous stroma. Of the seven PET, five were purely adenofibromatous, while two were mixtures of adenofibromatous and papillary components. Of the 31 ETLMP, 12 were adenofibromatous and 19 were either purely papillary or had mixtures of papillary and adenofibromatous components. An additional three ETLMP had one or more areas of microscopic invasion of the stroma in the form of an irregular or cribriform infiltration by atypical glands, often with squamous differentiation. These three neoplasms were designated "ETLMP with microinvasive carcinoma." The only neoplasm with extraovarian implantation at presentation, however, was an ETLMP with mixed adenofibromatous and papillary features, without microinvasion. None of the other patients with ETLMP had a metastasis or developed one within a follow-up period of between 0.8 and 11.2 years. Because they are very low-grade neoplasms, ETLMP should be separated from endometrioid carcinoma and not confused with PET, because PET have no malignant potential.     

术中超声在机器人辅助胰腺良性-低度恶性肿瘤手术中的应用价值

目的总结分析术中超声(Intraoperative ultrasound,IOUS)在机器人辅助胰腺良性-低度恶性肿瘤手术中的应用价值与经验。 方法回顾性分析2019年10月至2021年10月期间,术前诊断为胰腺良性-低度恶性肿瘤并由解放军总医院第一医学中心肝胆胰外科医学部行IOUS辅助下机器人胰腺肿瘤手术患者的临床及IOUS资料。 结果在147例患者中,IOUS能发现并定位全部肿瘤,130例(88.4%)可以明确肿瘤与主胰管的关系,23例(15.6%)在IOUS指导下改变了手术方式;IOUS辅助机器人胰腺肿瘤手术的平均手术时间(183.3±75.1)min,术后中位住院时间7 d,发生B级及以上胰瘘22例(15.0%),出现Clavien-Dindo Ⅲ级以上严重并发症15例(10.2%),无90 d死亡患者。 结论IOUS可以在术中辅助肿瘤定位,明确肿瘤与胆管、胰管的关系,发现术前影像学检查遗漏的隐匿病灶,在肿瘤切除后判断主胰管的连续性并判断胰管支撑管的位置,有利于手术决策的制订和减少术后并发症的发生,IOUS的应用为机器人辅助胰腺良性-低度恶性肿瘤手术的安全顺利实施提供了有利保障。