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Cell cycle regulatory protein expression by immunohistochemical assay may have diagnostic utility in the distinction of uterine leiomyosarcoma from leiomyoma variants. p16, p21, p27, and p53 protein expression was evaluated by immunohistochemistry on 44 atypical leiomyomas (mean follow-up, 50.8 mo), 16 leiomyosarcomas (mean follow-up, 29.7 mo), and 8 cellular leiomyomas (mean follow-up, 22.6 mo). Nuclear staining was semiquantitatively scored on 1 representative section per case as negative (0%), focal (0% to 33%), patchy (33% to 66%), or diffuse (66%). In addition, staining intensity was noted as weak, moderate, or strong. Proliferative index was gauged by Ki-67 and PHH3 immunohistochemical staining. One of 35 atypical leiomyoma patients with follow-up data developed an extrauterine recurrence 25.7 months after hysterectomy, whereas a second had intrauterine recurrence 24.9 months after myomectomy. Seven of 8 patients with leiomyosarcoma with follow-up had recurrence within the follow-up period, whereas there were no recurrences in patients with cellular leiomyoma. The Ki-67 proliferation index ranged from 0% to 25% in atypical leiomyoma (mean, 2%) and 6% to 50% in leiomyosarcoma (mean, 25%) with 0% to 10% in cellular leiomyoma (mean, 3%), whereas the PHH3 proliferation index ranged from 0% to 3% in atypical leiomyoma (mean,1%) and 0% to 10% in leiomyosarcoma (mean, 2%) with 0% to 2% in cellular leiomyoma (mean,1%). The atypical leiomyoma with extrauterine recurrence was diffusely positive for p21, but showed only weak focal (33%) staining for all other cell cycle markers. Uterine atypical leiomyomas, cellular leiomyomas, and leiomyosarcomas demonstrate a heterogenous pattern of cell cycle regulatory protein expression. Caution should be exercised in distinguishing leiomyosarcoma from atypical leiomyoma variants on the basis of cell cycle protein expression alone. In our study, cell cycle markers were not useful for predicting recurrence in atypical leiomyoma.

Atypical leiomyoma is a well-described smooth muscle neoplasm of the uterus. Only 1 study has addressed long-term clinical follow-up in a large series, and little is known about the adequacy of treatment by myomectomy. The surgical pathology archives were searched for consecutive cases of uterine atypical leiomyoma from 1992 to 2003. Glass slides were reviewed to confirm the diagnoses, and patient age, treatment modality, and clinical follow-up data were recorded. Fifty-one atypical leiomyomas with available glass slides and clinical follow-up data were identified. Thirty tumors exhibited diffuse, moderately to severely atypical cells, whereas 21 showed atypical cells in a more focal or patchy distribution. Twelve had ischemic-type necrosis. By the highest count method, 37 cases were found to have ≤1 MF/10 HPF, 13 showed 1 to 3 MF/10 HPF, and 1 was nearly entirely necrotic precluding mitotic assessment. Among cases in which adjacent non-neoplastic tissue was well visualized, all were found to have pushing margins (46 cases). The average tumor size was 6.8 cm (median 6.5 cm; range, 0.7 to 14 cm). The average patient age was 42.5 years (median 42 y; range, 21 to 72 y). In all cases, the initial diagnostic procedure was hysterectomy (34) or myomectomy (17). Average follow-up was 42 months (range, 0.3 to 121.8 mo). Of those treated with hysterectomy, 1 had recurrent atypical leiomyoma in the retroperitoneum at 87.5 months, 1 died of other causes, and the remaining 32 (94%) were free of disease. Of the myomectomy group, 82% had no evidence of recurrent disease on follow-up: 2 had residual atypical leiomyoma in the subsequent hysterectomy specimen; and 1 underwent second myomectomy for atypical leiomyoma with 2 subsequent successful pregnancies. Atypical leiomyoma has a low rate of extrauterine, intra-abdominal recurrence (

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 andor =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 (P0.001) and invasive implants (P0.001) were associated with decreased survival. When compared with typical S-LMP, S-LMP with micropapillary features were more strongly associated with invasive implants (P0.008) 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 (P0.001). 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.

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 or = 10 mf/10 hpf, four of 10 failed.(ABSTRACT TRUNCATED AT 400 WORDS)

Although the categorization of proliferative breast lesions provides valuable information regarding subsequent risk of breast cancer, the ability of pathologists to classify such lesions in a reproducible fashion has not been adequately evaluated. To assess further interobserver reproducibility in the categorization of proliferative breast lesions, six pathologists each reviewed 24 proliferative ductal lesions and classified them as either usual hyperplasia (H), atypical hyperplasia (AH), or carcinoma in situ (CIS). Before evaluation of the study slides, all the participants were instructed to use the diagnostic criteria of Page and co-workers and were provided with both a written summary of these criteria and a set of teaching slides with representative examples of each type of lesion. Complete agreement among all six pathologists was seen in 14 cases (58%); five or more agreed in 17 cases (71%); and four or more arrived at the same diagnosis in 22 cases (92%). No pathologist consistently rendered more "benign" or "malignant" diagnoses than any other. After assigning numerical values for each diagnostic category (H = 1, AH = 2, CIS = 3), the scores for the group of 24 cases did not differ significantly by pathologist (p = 0.68; average score range, 1.7-2.0). Our results indicate that with the use of standardized criteria, interobserver concordance in the diagnosis of proliferative ductal breast lesions can be obtained in the majority of cases.

Background 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. Objective We review Stanford's experience with diagnosing AVL and formulate a clinicopathologic approach to these lesions. Methods 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. Results 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. Limitations This retrospective study utilized a small number of cases from a single consultation service; therefore, some inherent selection bias may exist. Conclusion 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.

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.

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.

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.

The malignant fibrous histiocytomas (MFHs) are a histologically heterogeneous group of sarcomas that have been postulated to be derived from, or have the capacity to differentiate into, histiocytes. To determine whether MFH tumor cells actually express the features of histiocytes, i.e., bone marrow-derived cells of monocyte-macrophage lineage, we studied the antigenic and enzymatic phenotype of 13 MFHs in situ using frozen and plastic sections, respectively. Five pleomorphic three fibrous, two myxoid, two giant cell, and one histiocytic MFH were studied. While tumor cells in 12 of 13 cases were positive for HLA-A,B,C, tumor cells in all cases failed to express antigens present on bone marrow-derived macrophages, i.e., leukocyte common antigen (L3B12), HLA-DR, Leu-M3, and Leu-3a. Interestingly 8 of 13 cases were positive for CALLA. Although nonspecific, this may prove useful in differential diagnosis. Enzyme histochemistry demonstrated that tumor cells in 9 of 13 cases were positive for membrane 5' nucleotidase (5'N+). Four of these were also alkaline phosphatase positive (ALKP+). All cases were either negative or weakly positive for acid phosphatase (ACIDP) and alpha-naphthyl acetate esterase (ANAE). Tumor cells were unreactive for alpha-naphthyl butyrate esterase (ANBE) and adenosine triphosphatase (ATP). These findings indicate that MFH tumor cells do not express the enzymatic profile of cells of monocyte/macrophage lineage which are membrane 5'N-/ALKP- and ACIDP+/ANAE+/ANBE+/ membrane ATP+. In fact, these data suggest a similarity to fibroblasts which are membrane 5'N+, variably ALKP+, weakly ACIDP+/ANAE+, and ANBE-/membrane ATP-. Osteoclast-like giant cells present in two cases did express a histiocytic phenotype, suggesting that they are reactive elements not derived from admixed tumor cells. These results suggest that MFHs are primitive mesenchymal neoplasms, most likely sarcomas composed of poorly differentiated fibroblasts, and are unrelated to true histiocytic neoplasms.

Between 1959 and 1975, 256 patients with pathologic Stage I uterine adenocarcinoma were treated at Stanford University Hospital, Stanford, California. One hundred ninety-three patients were initially treated with surgery, and 63 received preoperative radium, reflecting different treatment philosophies of physicians operating at Stanford. Relapse rates for the two treatment groups were 9% (17 of 193) and 14% (9 of 63), respectively (P = 0.24). In both groups of patients, relapse rates were correlated with grade, although for those treated with initial surgery myometrial invasion was a much better predictor of relapse. Only one of the 127 patients without demonstrable myometrial invasion suffered a possible relapse. Sixteen of 66 patients with myometrial invasion (24%) relapsed after treatment. A review of the histologic material revealed 26 of 256 cases with a special histologic variant termed uterine papillary serous carcinoma, which was associated with a high relapse rate (50%) and a marked tendency for upper abdominal spread. It was found that the use of preoperative intracavitary radium was not demonstrated to be of value. Histologic information obtained from the hysterectomy specimen can be used to determine patients at high risk for relapse who may benefit from adjuvant treatment based on our understanding of the natural history of endometrial carcinoma.

Examples of focal clearing of endometrial epithelial nuclei associated with the presence of trophoblastic tissue have been oberved recently in our surgical pathology laboratories. These nuclear alterations were initially observed in endometria from first and second trimester spontaneous abor

The design and details of a prospective, randomized study protocol involving bipedal lymphography, and exploratory laparotomy with selective node biopsy in patients with apparently localized adenocarcinoma of the prostate are presented. The analysis includes the results of selected diagnostic tests, and an assessment of the accuracy of clinical vs. surgical staging in 50 unselected patients. Lymphatic metastases were found at the time of diagnostic laparotomy in 18 of the 50 patients (36%). Both increasing size (advanced T stage) and decreasing differentiation of the primary tumor were associated with an increased incidence of lymph node metastases. Of 25 patients with T1 and T2 tumors (Stage B), and 25 patients with T3 tumors (Stage C), lymphatic dissemination was found in 20 and 52%, respectively. Eleven of 20 patients (55%) with poorly differentiated tumors had lymph node metastasis, compared with only 2 or 11 patients (18%) with well-differentiated tumors. Twelve patients had a change in their clinical stage following exploratory laparotomy; in eight the stage was increased and in four it was decreased. Of 18 patients with lymphatic metastases, some of which were extensive and most of which were associated with increased serum acid phosphatase values, no evidence of concurrent bony or visceral dissemination was found. Although preliminary, this finding should stimulate the search for effective treatment in these patients who were previously thought to be incurable on the basis of probable vascular dissemination.

Of 256 patients with carcinoma confined to the uterine corpus at the time of hysterectomy treated in the period 1959-1975 at Stanford University Hospital, 98 patients (38%) had neoplasms which demonstrated at least focal intracytoplasmic mucin. In 21 carcinomas (9%), intracytoplasmic mucin production was the dominant form of differentiation--a group which we designate primary mucinous carcinoma of the endometrium. Freedom from relapse and frequency of myometrial invasion were not statistically different for patients whose neoplasms contained intracytoplasmic mucin, regardless of the amount of mucin present, when compared with cases of nonmucin-containing carcinoma. Using histochemical methods, it was impossible reliably to distinguish between the intracytoplasmic mucin produced by carcinomas arising in endometrium and that produced by carcinomas primary in the endocervix. Differential biopsy and fractional curettage are stressed as useful tools in making this clinically important distinction. Since both benign mucinous metaplasia and mucinous carcinoma may arise in the endometrium, it is important to establish histopathologic criteria by which the malignant lesions may be recognized. The use of criteria illustrated in this paper (which include architectural complexity of proliferation, epithelial stratification, loss of epithelial polarity, and nuclear atypicality) resulted in the recognition of mucin producing proliferations which as a group manifest a 50% incidence of myometrial invasion.

Three cases of hemorrhagic necrosis of the breast after Dicumarol therapy are presented. Hemorrhagic necrosis has a distinctive gross appearance which should be recognized easily and occurs almost inevitably between the third and eighth day of anticoagulant therapy. The definite time of onset and appearance should make the diagnosis simple. Vasculitis, extensive hemorrhage, and necrosis are seen histologically. Surgical therapy is usually necessary to prevent infection and slough of the breast. The necessity of separating the necrotic lesion from simple hemorrhage is emphasized.

Two patients with cystinosis in end stage renal failure received renal transplants from parental (heterozygous) donors. Although initial renal function was excellent, rapid glomerular insufficiency ensued between the third and sixth post-transplant months, without the reappearance of the Fanconi syndrome. Biopsies disclosed nephron loss, interstitial edema and fibrosis, and moderate infiltration with lymphocytes, plasma cells, and blast cells. The glomeruli showed mild to marked membranous and proliferative changes. One biopsy specimen demonstrated intracellular deposits of cystine crystals. These changes do not permit an assessment of the relative roles of systemic cytinosis, cell-mediated immune rejection, or antibody-mediated damage. The implications of these findings for future transplants in cystinotic children are discussed.

Ten cases diagnosed as epidermoid carcinoma arising in the sinus tracts of chronic osteomyelitis have been reviewed. In two cases there were histologically proved metastases. Attention has been called to the signs and symptoms associated with carcinomatous change. The investigation of such a patient includes roentgenographic study of the limb and chest and a search for metastases in the regional lymph nodes and liver. A biopsy will guide the management. The histological diagnosis may be difficult because of pre-existing and coexisting metaplasia and pseudoepitheliomatous hyperplasia, which simulate cancer. The benign group should have extirpation of the sinus tracts and eradication of the osteomyelitis. Patients with atypical pseudoepitheliomatous hyperplasia and epidermoid carcinoma should have amputation at an adequate level and biopsy of suspicious regional lymph nodes. None of the three deaths in this series could be attributed to epidermoid carcinoma arising in osteomyelitis.

Endodermal sinus tumor is the most common testicular neoplasm in childhood. The management of children with this neoplasm remains controversial. We have treated prospectively 5 children with stage I endodermal sinus tumor with limited surgery and no adjuvant therapy. The median patient age at diagnosis was 21 months (range 5 to 24 months). All children underwent an inguinal orchiectomy with high ligation of the spermatic cord. Retroperitoneal node dissection was not performed in any case and no child received adjuvant chemotherapy or radiation therapy. All patients were well without evidence of recurrent disease at a median followup of 46 months (range 19 to 72 months). Because these tumors usually are localized at the time of diagnosis, rarely spread to the retroperitoneal nodes and have a biological marker in most cases, and because good salvage chemotherapy is available for patients with relapse, we believe that nonmetastatic testicular endodermal sinus tumors in children can be managed with radical orchiectomy alone. Retroperitoneal node dissection is not necessary and adjuvant therapy is not indicated if markers return to normal. Further treatment should be reserved for the rare child with relapse.

One-hundred-eleven cases of histopathologically atypical or malignant lipomatous lesions in the somatic soft tissue and retroperitoneum were studied. These consisted of 48 differentiated fatty neoplasms of the somatic soft tissues (DFT-S), 21 fatty neoplasms of the retroperitoneum (DFT-R), 33 myxoid liposarcomas from various sites and nine pleomorphic liposarcomas. DFT-S were defined as lipomatous lesions composed of mature fat and containing atypical stromal cells or lipoblasts. In the somatic soft tissues, this group included lesions that would be classified using published criteria as "atypical lipoma", "pleomorphic lipoma", "well-differentiated lipoma-like liposarcoma", and "sclerosing liposarcoma". All of the DFT-R met previously published criteria for "well differentiated liposarcoma" or "sclerosing liposarcoma". We found no consistent histologic differences between the DFT-S and DRT-R. No pure "round cell" liposarcomas were encountered although many myxoid liposarcomas had "round cell" areas. Follow-up data were available in 80 cases (72%) with a mean follow-up period of over 7 years. Among the DFT-S there were no uncontrollable recurrences, distant metastases, or tumor-related deaths. The depth of the neoplasm correlated with the tendency for local recurrence; no neoplasms primary in the subcutis recurred; 29% of the tumors recurred when they originated in the deep soft tissues or within the muscle. None of the recurrent tumors demonstrated "dedifferentiation." DFT-R had a recurrence rate of 67% and, although there were no distant metastases, nine patients (43%) died of tumor. Five retroperitoneal tumors dedifferentiated but did not metastasize. In light of this experience, we believe that the term "atypical lipoma" is warranted for the DFT-S and "well differentiated liposarcoma" is an appropriate label for the DFT-R. The overall mean survival for the 52 cases of liposarcoma (excluding DFT-S) was 13.6 years. The mean survival in "well differentiated liposarcoma" (11.25 years) was between that for myxoid liposarcoma (16.25 years) and that for pleomorphic liposarcoma (7 years). Six patients (29%) with myxoid liposarcoma developed local recurrences and 6 patients (29%) developed distant metastases and died. Metastasis was always associated with a round cell (or pleomorphic) component with increased numbers of mitotic figures in either the primary tumor or a local recurrence.

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.

The ultrastructural features of two "sex cord tumors with annular tubules" are presented. The findings are compared with the reported fine structure of ovarian and testicular stromal cells and the cells of gonadal stromal neoplasms. The predominant cell in the "sex cord tumor with annular tubules" has some of the ultrastructural features found in gonadal stromal cells of either ovarian or testicular type; however, no Charcot-Bottcher crystals, lamellar bodies, crystalloids of Reinke, abundant smooth endoplasmic reticulum or complex plasma membrane interdigitations are observed in the tumor cells to suggest wither Sertoli or Leydig cell origin. The striking similarity between the predominant cell type and granulosa cells, as well as the presence of fibrillary material of the type seen in Call-Exner bodies, suggests a granulosa cell origin for these neoplasms. However, the presence of a sparsely distributed second cell type which closely resembles the dark cells in normal nonluteinized ovarian stroma indicates these tumors may arise from the nonspecialized ovarian stroma.

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.

A review of 256 cases of pathologic Stage I uterine adenocarcinoma treated at Stanford University Hospital revealed 26 cases of uterine papillary serous carcinoma (UPSC), a clinically aggressive and morphologically distinct variant of adenocarcinoma which closely resembles ovarian papillary serous carcinoma. These lesions are easily recognized by microscopic examination and typically feature a high degree of cytologic anaplasia and a papillary growth pattern. Invasion of the lymphatics has been a frequent finding. The relapse rate among patients with pathologic Stage I UPSC was 50% (13/26), five times the rate which would have been predicted by the incidence of UPSC. Patients with Stage I UPSC fared significantly worse than the group of nonpapillary grade II or grade III adenocarcinomas (p less than 0.0001). Forty percent of Stage I UPSC patients had deep myometrial invasion, as compared with 12% of those with all other histologic types of adenocarcinoma (p = 0.001). Women with UPSC deeply invading the myometrium tended to do worse than those with deeply invasive lesions of the more usual endometrioid type as reflected by relapse rates (after surgery alone) of 63% and 30%, respectively. Of seven Stage I corpus carcinoma patients whose initial site of failure was in the upper abdomen, six had UPSC. Thus, UPSC shares the tendency of its ovarian counterpart to spread over peritoneal surfaces. In addition to the original study group of 26 Stage I patients, 34 patients with more advanced stages of UPSC were also reviewed. Of these, 26 have been followed and four survive. Eleven of these women presented or relapsed with abdominal carcinomatosis. UPSC is a clinically aggressive neoplasm which should be distinguished from other types of primary endometrial adenocarcinoma. In cases of invasive UPSC the mode of spread, similar to that of ovarian surface epithelial carcinomas, suggests the need for adjuvant upper abdominal and pelvic irradiation or effective chemotherapy.

A clinical and histologic review of 25 patients with melanocytic lesions classified as desmoplastic malignant melanoma is reported. All of the lesions were located in sun-exposed sites. The average age was 61.2 years (range, 38 to 83), with a median age of 56. There were 14 female and 11 male patients. Desmoplastic malignant melanoma is a melanocytic and fibroblastic proliferation that occurs predominantly in the head and neck area. The bland constituent cells resemble fibroblasts and are often arranged in bundles or fascicles, which may be arrayed perpendicularly to the overlying epidermis. Enlarged and/or atypical cells are usually scattered among the spindled cells. Most, but not all, of the tumors (24 of 25 in this series) are associated with lentigo maligna or an atypical junctional melanocytic proliferation. Mitotic figures are always found within the constituent cells of the fibrous-appearing mass, and neurotropism may be present. Patients with desmoplastic melanoma typically present with a mass, which is occasionally associated with a pigmented lesion. The lesions in our series were deeply invasive to level IV or V. Lentigo maligna and a dermal fibroblastic-appearing mass containing atypical cells arranged in fascicles are the most common morphologic features found in desmoplastic melanoma. Follow-up data is available for 23 patients. The average length of follow-up was 2.7 years (range, 0.1 to 9 years). Eighteen patients were observed for 3 or more years. Twelve patients developed local recurrences, and five developed metastases; three of the patients with metastases had a local recurrence before the development of metastases. Three of the patients with metastatic melanoma died of tumor between 2 and 4 years after their initial excision. Eight of the 12 locally recurring lesions were either diagnosed initially as a benign lesion or histologic examination was not performed on the initial excision specimen. It appears that recurrence may be related to inadequate initial therapy.