Emeritus Faculty, Acad Council, Pathology
Clinicopathologic studies in endometrial carcinoma, ovarian neoplasms, and soft tissue tumors.
Post-radiotherapy atypical vascular lesions (AVL) in mammary skin show significant clinical and histopathologic overlap with well-differentiated angiosarcoma (AS) and pose a considerable diagnostic and managerial challenge when encountered.We review Stanford's experience with diagnosing AVL and formulate a clinicopathologic approach to these lesions.We performed a clinicopathologic study on 11 cases that were initially diagnosed as AVL and examined whether there are specific clinical or histopathologic features that delineate AVLs from well-differentiated AS.Clinically, all patients were women with a mean age of 68.1 years, had a history of infiltrating breast carcinoma, and were treated by excision with postoperative radiation therapy. All lesions were located in mammary skin within the prior radiation field. The clinical presentation included erythema, telangiectasias, papules, plaques, and nodules. All patients were diagnosed with AVL on initial biopsy. Six patients showed no recurrence or progression of disease following incomplete excision with no further therapy (3/6) or re-excision with negative margins (3/6). The remaining 5 patients were shown to have AS in the re-excision specimen. The patients diagnosed with AS were older and had a shorter interval from radiation as compared to those who did not experience an adverse outcome. Histologically, all initial biopsy specimens were transected and were characterized by complex, anastomosing vascular proliferations with dilated spaces. Each case was morphologically evaluated according to the AVL criteria of Fineberg and Rosen. Three cases met all of the criteria for AVL, and these patients showed no progression of disease. The remaining cases met most but not all diagnostic criteria for AVL and showed some features of AS, but fell short of a definitive diagnosis of AS, including the 5 cases that were subsequently diagnosed as angiosarcoma.This retrospective study utilized a small number of cases from a single consultation service; therefore, some inherent selection bias may exist.We could not identify unequivocal clinical or histologic criteria that allows for a sharp separation between AVL and AS. Dermatologists and pathologists need to be aware of the overlap between AVL and well-differentiated AS and all patients who receive a diagnosis of AVL should undergo complete excision with close clinical follow-up and biopsy of any new lesions.
View details for DOI 10.1016/j.jaad.2006.10.025
View details for Web of Science ID 000247577500016
View details for PubMedID 17572278
The purpose of this multicenter, double-blind, randomized, parallel-group study was to determine the effect of thirteen 28-day cycles of drospirenone combined with estradiol, compared with estradiol alone, on the endometrium of postmenopausal women.Postmenopausal women not on hormone therapy but with an intact uterus were enrolled (N = 1,147); 1,142 were evaluated. Participants were randomly assigned to treatment with 1.0 mg of estradiol alone (E(2) monotherapy) or 1.0 mg of estradiol plus 0.5, 1.0, 2.0, or 3.0 mg of drospirenone (DRSP/E(2)). Endometrial biopsies were performed at baseline, at 7 months if indicated, and at study end in the 13th month. Safety was evaluated with peripheral blood samples for hematology, liver and renal function, and lipids, along with vital signs and interval medical evaluations.When compared with estradiol alone, combinations of drospirenone and estradiol were effective in protecting against endometrial hyperplasia. The probability of hyperplasia was 0.060 (95% CI, 0.043-0.078) for the E(2) monotherapy group, 0.007 for the 2-mg DRSP/E(2) group, and nonsignificant for the remaining drospirenone/estradiol groups. Endometrial bleeding decreased in all treatment groups over time. The combination of drospirenone and E(2) relieved menopausal symptoms and resulted in improvements in health-related quality-of-life measures. There were no significant adverse events, and effects on triglycerides, total cholesterol, and high-density lipoprotein cholesterol were positive.The use of drospirenone combined with estradiol provides protection against endometrial hyperplasia, reduces endometrial bleeding with time, and relieves menopausal symptoms. There were no safety issues and blood pressure was reduced in women with hypertension.
View details for DOI 10.1097/01.gme.0000177318.24005.b1
View details for Web of Science ID 000233453700012
View details for PubMedID 16278615
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.
View details for Web of Science ID 000229348500001
View details for PubMedID 15897738
The family of lesions thought to be composed at least in part of perivascular epithelioid cells, characterized as HMB-45-positive epithelioid cells with clear to eosinophilic granular cytoplasm and a propensity for a perivascular distribution, includes some forms of angiomyolipoma and lymphangioleiomyomatosis, as well as clear cell "sugar" tumor (CC-SUGAR). When composed predominantly or exclusively of epithelioid cells, it has been suggested that these lesions be classified as "perivascular epithelioid cell tumors" (PEComa). Four cases of uterine PEComa have been described in the literature, three of which exhibited aggressive behavior. We report the clinical, histologic, and immunohistochemical features of eight more examples of uterine PEComa. Patients ranged in age from 40 to 75 years (mean 54 years). Most patients presented because of abnormal uterine bleeding, and grossly a mass was present in the uterine corpus. Morphologically, the tumors could be divided into two groups (A and B). Group A tumors demonstrated a tongue-like growth pattern similar to that seen in low-grade endometrial stromal sarcoma and were composed of cells that tended to have abundant clear to eosinophilic pale granular cytoplasm, diffuse HMB-45 expression, and focal muscle marker expression. Group B tumors were composed of epithelioid cells with less prominent clear cell features, smaller numbers of which were HMB-45-positive. They also featured extensive muscle marker expression and a lesser degree of the endometrial stromal sarcoma growth pattern seen in group A tumors. Two of the four patients with group B tumors had pelvic lymph nodes involved by lymphangioleiomyomatosis, and one of these patients had the tuberous sclerosis complex. Seven of the eight patients with PEComas were treated by hysterectomy. All eight patients are alive and well, although follow-up of >2 years was available only for two patients. Uterine epithelioid smooth muscle tumors and low-grade endometrial stromal sarcomas were compared with the PEComas. Group A PEComas, group B PEComas, and epithelioid smooth muscle tumors were all parts of a continuous histologic spectrum, with group A PEComa at one end of the spectrum and epithelioid smooth muscle tumors at the other, while group B tumors shared features of both. PEComa was histologically and immunohistochemically distinct from endometrial stromal sarcoma. Our data and a review of the literature indicate that PEComa is a subset of HMB-45-positive epithelioid mesenchymal tumors of the uterus with an uncertain relationship to pure smooth muscle tumors. Although none of the patients in this study experienced recurrence during a short follow-up period, some reported in the literature have had recurrences; consequently, we think uterine PEComa should be considered a tumor of uncertain malignant potential until long-term outcome data for a larger number of patients become available.
View details for Web of Science ID 000173097600001
View details for PubMedID 11756764
View details for PubMedID 11112225
View details for PubMedID 8795835
A recent trend in the classification of uterine smooth muscle neoplasms (USMNs) into clinically benign and clinically malignant groups has been to move from exclusive reliance upon mitotic index (MI) to an approach that incorporates additional histopathologic characteristics. In furtherance of this goal, we assessed a variety of histopathologic features of 213 problematic smooth muscle neoplasms for which we had > or = 2 years of clinical follow-up data or for which there was an unfavorable outcome. One hundred and thirteen of these patients have had a minimum follow-up of 5 years, and 48 have been followed for > or = 10 years. Cases eliminated from the study group included USMNs with a significant myxoid or epithelioid component and cases of intravenous leiomyomatosis. USMNs, whether cellular or not, with no cytologic atypia and with a mitotic index (MI = number of mitotic figures [mf]/10 high-power fields [hpf]) of < 5 mf/10 hpf (usual leiomyomas) were also excluded unless they had unusual features or were associated with an adverse clinical outcome. Fifty-six patients were initially treated by myomectomy or another form of local tumor removal; the remainder had a hysterectomy. From a wide variety of light microscopic features assessed, the important predictors that emerged, using a variety of data exploratory techniques, were MI, the degree of cytologic atypia, and the presence or absence of coagulative tumor cell necrosis (CTCN). Stratification of the USMNs with respect to these three features resulted in a five-group classification of USMNs with the following major characteristics. Group 1: Of the 89 USMNs with an MI in the range 5 < or = MI < 20 without CTCN and with no more than mild atypia, 88 were clinically benign. One patient with a tumor in this group died of metastatic disease 96 months after her uterine cervical primary neoplasm was removed. Combining our data with that in the literature, the failure rate in this group is approximately 1/200 (0.5%). This low failure rate warrants the use of the label "leiomyoma with increased mitotic index" for USMNs with these histologic features. Two patients whose USMNs were characterized by mild atypia, no necrosis, and MI < 5 developed identical-appearing pulmonary metastases and were judged in retrospect to have the syndrome "benign metastasizing leiomyoma." Group 2: USMNs with no CTCN and diffuse moderate to severe atypia fell into two groups based on the MI. For those patients whose neoplasms had an MI > or = 10 mf/10 hpf, four of 10 failed.(ABSTRACT TRUNCATED AT 400 WORDS)
View details for Web of Science ID A1994NL61500001
View details for PubMedID 8179071
We present the results of a clinicopathologic study of 20 patients with primary extrauterine endometrial stromal sarcoma (ESS). The sites of the primary neoplasm and the number of patients with sufficient follow-up for survival analysis are as follows: ovary (three of four), fallopian tube (one of one), pelvic cavity (six of eight), abdominal cavity (five of six), and retroperitoneum (one of one). Evaluation of all patients included the mitotic index (MI) and cytologic atypia. Thirteen of the sixteen patients eligible for survival analysis had tumors with an MI < 10 and would be classified as low-grade stromal sarcomas in the Norris and Taylor scheme. Eight (62%) of the 13 had one or more relapses; of these, three died of disease at 35, 108, and 120 months, respectively, and another patient was alive with disease at 96 months. The other four patients who were treated after a relapse showed no evidence of disease after relapse at 36, 57, 63, and 146 months, respectively. Two of the 13 patients had tumor considered unresectable at the time of diagnosis; both died of disease at 5 and 10 months, respectively. Neither MI nor cytologic atypia were predictive of tumor recurrence or death from tumor. We also extracted clinical and morphologic data from all previous reports of primary extrauterine ESS, combined them with our 20 patients, and then compared the combined group with 17 cases of primary high-stage uterine ESS we presented in an earlier report. Not surprisingly, the behavior of the primary extrauterine ESS was more reminiscent of high-stage primary uterine ESS than low-stage primary uterine ESS.
View details for Web of Science ID A1993LZ01200001
View details for PubMedID 8253545
Well-differentiated mucinous ovarian neoplasms fall into several more or less distinct morphologic groups. One of the major problems, however, is correlation of morphologic groups with clinical outcome. The authors analyze this problem in regard to the major morphologic distinctions, morphologic syndromes, and taxonomic quandaries, concluding with an overview of miscellaneous significantly related topics.
View details for PubMedID 9420922
Benign ovarian neoplasms with endometrioid or clear-cell differentiation are rare, but benign Brenner tumors are not unusual. A subgroup of endometrioid, clear-cell, and Brenner neoplasms, characterized by morphologic features intermediate between benign and malignant, has been labelled by various investigators as borderline, of low malignant potential (LMP), or proliferating. This chapter reviews the definition of each of these cell types, evaluates the significance of the LMP category, and concludes with a discussion of well-differentiated ovarian neoplasms with mixed differentiation of the müllerian type.
View details for PubMedID 9420923
Serous neoplasms of the ovary, which constitute the largest subgroup of the surface epithelial tumors, cluster into three distinctly clinicopathologic groups: benign neoplasms, which are architecturally noncomplex, confined to the ovary, and composed of cytologically bland cells; carcinomatous neoplasms, which have spread beyond the ovary and are cytologically malignant; and an intermediate group, which raises serious problems in taxonomy, differential diagnosis, and prognosis. This chapter focuses on differential diagnosis, emphasizing the authors' experience as well as reports from other investigators.
View details for PubMedID 9420921
Because clinical outcome in patients with malignant surface epithelial neoplasms (M-SENs) of the ovary is highly varied, stratification of patients into favorable and unfavorable prognostic groups is an important clinicopathologic function. This chapter analyzes the various prognostic factors, with an emphasis on M-SENs of grades II and III.
View details for PubMedID 9420924
Considerable progress has been made over the last several years toward understanding the significance of noninvasive epithelial changes in the breast. This progress, in essence, is the result of categorizing in situ alterations according to their clinical significance, or more specifically, according to the risk that such lesions carry to the patient for development of a subsequent invasive carcinoma. This article summarizes the histopathological criteria that are currently used to define morphologic categories and, perhaps more importantly, it reviews the clinical implications of the diagnoses that result from this categorization.
View details for PubMedID 9420916
In the context of recent developments, the role of the surgical pathologist in evaluating and reporting breast cancer specimens has become more important. The pathologist must not only diagnose carcinoma in a given patient, but must also document a set of morphologic features that have been shown to be important in determining prognosis and guiding therapy.
View details for PubMedID 9420919
The clinicopathologic, immunohistochemical, and flow cytometric characteristics of 34 cases of mammary carcinoma with metaplasia were compared with those of 20 cases of pure sarcoma of the breast. All 20 of the latter tumors showed the pattern of malignant fibrous histiocytoma. There were 20 cases of carcinoma with mesenchymal metaplasia, 7 cases of carcinoma with mixed epithelial (squamous) and mesenchymal metaplasia, and 7 cases of carcinoma with epithelial metaplasia (four mixed ductal/squamous and three pure squamous cell carcinomas). No patient with pure sarcoma had lymph node metastases develop; all nodal metastases were found in patients who had carcinoma with metaplasia, although in one case the carcinomatous component was seen only within a lymph node metastasis. Epithelial antigens were found not only within the epithelial elements of all cases of carcinoma, but also within the apparent mesenchymal elements of 44% of the carcinomas showing divergent differentiation. Flow cytometric analysis of eight cases of carcinoma with mesenchymal metaplasia showed aneuploidy/tetraploidy in six neoplasms. For patient management purposes, the distinction of pure sarcoma from carcinoma with metaplasia is important, but additional subclassification of carcinoma with metaplasia is of greater biologic than clinical interest.
View details for Web of Science ID A1991FK91100004
View details for PubMedID 1850949
We have presented an unusual case of chondroblastoma mimicking a malignant tumor. Retrospective review of radiographs obtained 19 years before the diagnosis gave us a unique opportunity to follow the natural history of this atypical lesion.
View details for PubMedID 2057799
We present the results of a clinicopathologic study of 109 patients with endometrial stromal sarcoma and eight patients with endometrial stromal nodule. Of the 109 patients with endometrial stromal sarcoma, follow-up was obtained on 93 (85%). The stage distribution of the patients with stromal sarcoma and the number of patients with follow-up (numerator) compared to the total number of patients in each stage (denominator) are: Stage 1, 73/85; Stage II, 3/6; Stage III, 11/11; Stage IV, 6/7. Stage II patients are considered separately in the analysis. Thirty-six percent of the Stage I patients experienced one or more relapses. Of these, six (23%) died of disease from 11 to 360 months from diagnosis (median, 79 months). Nine (35%) were alive with disease. Of the eleven Stage III patients, eight had one or more relapses and of these, six died of disease. Of the six Stage IV patients, five had one or more relapses and of these, three died of disease. The outcome differences between Stages I, III, and IV are statistically significant (p less than .01). Microscopic features evaluated included the mitotic index (MI = number of mitoses/10 high-power fields) and cytologic atypia. Forty-five percent of Stage I patients who had both rare mitotic figures and minimal atypia had one or more relapses and of these, two (13%) died of disease at 85 and 360 months, respectively. Thus, neither MI nor cytologic atypia were predictive of tumor recurrence for patients with Stage I tumors.
View details for Web of Science ID A1990DA42600002
View details for PubMedID 2327549
To determine whether the mononuclear cells (MC) and multinucleated giant cells (GC) of giant cell tumor of tendon sheath (GCTTS) exhibit evidence of monocyte/macrophage lineage, we studied their antigenic features (seven cases, paraffin sections; two cases, frozen sections) and enzymatic features in situ (four cases, plastic sections). Both MC and GC expressed a monocyte/macrophage phenotype: HLA-A,B,C+, HLA-DR+, T200+ (leukocyte common antigen), Leu-M3+ and Leu-3+. MC and GC also expressed similar enzymatic phenotypes which resembled that of osteoclasts. Both were rich in acid phosphatase and contained smaller, variable amounts of ATPase, beta-glucuronidase, alpha-naphthyl acetate esterase, and 5'-nucleotidase. Both lacked alkaline phosphatase. Reactive osteoclasts in plastic and paraffin sections were also T200+, a finding strongly supporting their bone marrow derivation and leukocytic differentiation. In plastic sections, osteoclasts were additionally reactive with macrophage antigen EBM11. In aggregate, these data suggest that GCTTS is a true histiocytic lesion of monocyte/macrophage lineage composed of phenotypically similar MC and GC that most closely resemble osteoclasts. We found no evidence that GCTTS cells resemble osteoblasts, fibroblasts, or synovial sarcoma cells. Furthermore, expression of the Ki-67 nuclear antigen by 1-2% of MC but not by GC suggests that the proliferating cells in GCTTS are restricted to its MC component.
View details for Web of Science ID A1988N721200004
View details for PubMedID 2837101
The first part of this review includes a discussion of some issues in decision analysis as it applies to uterine mesenchymal tumors, as well as a discussion of some of the morphologic features and histochemical techniques that may be used to determine whether a mesenchymal tumor is demonstrating smooth muscle or endometrial stromal differentiation. Also included in the first part are caveats that the pathologist should observe before interpreting mesenchymal tumors of the uterus. The second part of the paper is devoted to morphologic diagnostic criteria and differential diagnosis.
View details for Web of Science ID A1988N317100003
View details for PubMedID 3041510
Thirty-five patients with superficial transitional carcinoma of the bladder were treated intravesically with escalating doses of recombinant alpha-2-interferon administered weekly for 8 weeks. Of the 19 patients with high-grade intraepithelial neoplasia (17 carcinoma in situ [CIS], two severe dysplasia, all cytology positive), six (32%) had complete resolution of all histologic and cytologic evidence of disease (complete response). An additional three patients (16%) had complete resolution of CIS, but the interval appearance of a low-grade transitional cell neoplasm. Five (26%) had a partial response (complete resolution of all evidence of CIS on multiple bladder biopsies but persistently positive cytologic preparations). Sixteen patients with recurrent papillary tumors and extensive prior therapy were also treated. Four (25%) had a complete response. Twenty-three of the 35 patients had prior intravesical therapy. Seven of the 23 (30%) patients with prior intravesical chemotherapy or immunotherapy had a complete or partial response to interferon, while eight of the 12 patients (67%) without prior intravesical treatment responded. These responses were achieved with minimal local and systemic toxicity. Of the ten complete responders, five remain in continuous unmaintained remission for 18+ to 37+ months. Intracavitary alpha-2-interferon is an effective new treatment for some patients with bladder cancer.
View details for Web of Science ID A1988M715400011
View details for PubMedID 3280742