Prognostic factors in invasive bladder carcinoma in a prospective trial of preoperative adjuvant chemotherapy and radiotherapy.

Clinical and pathologic factors were analyzed in 40 patients with localized muscle-invasive bladder carcinoma treated in a prospective bladder-preserving program consisting of transurethral tumor resection, neoadjuvant chemotherapy (methotrexate, cisplatin, and vinblastine [MCV]), and 4,000 cGy radiotherapy with concurrent cisplatin. Patients with biopsy-proven complete response after chemotherapy and 4,000 cGy radiation received full-dose radiotherapy (6,480 cGy) with cisplatin. Cystectomy was recommended to patients with residual disease. Distant metastasis rate was associated with tumor stage and size: 0% in T2 patients, 39% in T3-4 patients (P = .035), 6% for tumors less than 5 cm, and 59% for tumors greater than or equal to 5 cm (P = .002). Risk of bladder tumor recurrence was higher in patients with tumor-associated carcinoma in situ (CIS; 40%) than those without CIS (6%; P = .075). Papillary tumors and solid tumors both had similar treatment outcomes. By multivariate analysis, tumor stage T2 (P = .04) and absence of CIS (P = .03) were significant predictors of complete response; CIS was predictive of local bladder recurrence (P = .07); and tumor size (P = .03), response after chemoradiotherapy (P = .02), and vascular invasion (P = .08) were associated with distant metastasis. Six of eight local bladder tumor recurrences were superficial tumors. The low actuarial distant metastasis rate of T2 patients (0% at 3 years), the 3-year actuarial overall survival rates for T2 (89%) and T3-4 (50%) patients, and the similar treatment outcomes for papillary versus solid tumors are encouraging when compared with published historical controls. These results provide preliminary evidence (median follow-up, 30 months) that the current chemoradiotherapy regimen may have beneficial effects in the treatment of muscle-invasive bladder carcinoma. The true efficacy of neoadjuvant chemotherapy remains to be proven by ongoing randomized trials.

Estrogen agonist and antagonist action on the human estrogen receptor in Drosophila.

The estrogen receptor (ER) regulates the expression of genes involved in the growth, proliferation and differentiation of skeletal, cardiovascular, neural and reproductive tissues. A basic scheme for the mechanism for ER action has been developed, but precise details on the interactions between ER and the cellular signaling and transcription machinery required for receptor-mediated regulation of specific target genes are still lacking. We have developed a genetic approach to explore the functional interactions of ER. In this work, we describe the development of an estrogen responsive system in the fruit fly, Drosophila melanogaster. Transgenic flies carrying the human ER alpha and an estrogen responsive green fluorescent protein (GFP) reporter gene were constructed. In vivo expression of the GFP reporter gene was observed when larvae were grown on a food source containing steroidal or nonsteroidal estrogens. The induction of the reporter gene by estrogens was blocked upon treatment with tamoxifen, an estrogen antagonist. However, we failed to recapitulate ligand-independent activation of the receptor in vivo or in cultured Drosophila cells. An estrogen responsive Drosophila system could be used to identify and characterize the complex functional interactions between ER and the other components of the cellular transcriptional apparatus.

A mutation in the follicle-stimulating hormone receptor occurs frequently in human ovarian sex cord tumors.

A subset of ovarian tumors, referred to as sex cord-stromal tumors, produce endocrine manifestations due to the secretion of estrogens or androgens. Because gonadotropins induce the growth, differentiation, and function of the steroid-producing cells of the ovary, we hypothesized that mutations in the FSH receptor (FSH-R) might occur in this group of tumors. Ovarian sex cord tumors (n = 13), small cell carcinomas of the ovary (n = 3), and control DNA specimens (n = 116) were screened for mutations in the transmembrane domains of the FSH-R. A heterozygous T-->C mutation was found at nucleotide 1777 that converts codon 591 from phenylalanine to serine (F591S). This sixth transmembrane domain mutation was found in 9 of 13 (69%) sex cord tumors and 2 of 3 ovarian small cell carcinomas, but it was not present in control specimens, including 5 normal ovaries, 5 nonsex cord ovarian tumors, 16 thyroid tumors, or 90 specimens of peripheral blood leukocyte DNA, suggesting that this nucleotide change is not a polymorphism. The functional effects of identified mutations were assessed by expression of the wild-type or the F591S mutant FSH-R in COS-7 cells. The F591S mutation eliminated FSH-stimulated cAMP production, and a similar effect was observed when this mutation was introduced into the homologous location of the LH receptor. The high prevalence of the F591S mutation in the FSH-R suggests that it plays a role in the development of ovarian sex cord tumors.

Pulmonary vascular changes in scleroderma.

To determine the incidence and significance of pulmonary vascular changes in scleroderma, all necropsy reports of patients with scleroderma who died at the Massachusetts General Hospital were analyzed and correlated with clinical data. The records of 30 such patients were available. Fourteen had moderate or marked abnormalities in the pulmonary arterial tree. Nine of these 14 patients had predominantly respiratory symptoms. The arterial changes consisted pathologically of intimal and medial hyperplasia affecting pulmonary arteries of all sizes. Of the eight patients with the most severe pathologic changes in the pulmonary arteries, five had slight or no interstitial fibrosis. Three of these five patients had rapidly progressive respiratory failure and severe pulmonary hypertension leading to death. Such cases form a distinct clinicopathologic entity of malignant pulmonary hypertension in scleroderma, comparable to the better recognized entity of malignant renal hypertension in scleroderma.

Advanced prostate cancer: the results of a randomized comparative trial of high dose irradiation boosting with conformal protons compared with conventional dose irradiation using photons alone.

PURPOSE: Following a thorough Phase I/II study, we evaluated by a Phase III trial high versus conventional dose external beam irradiation as mono-therapy for patients with Stage T3-T4 prostate cancer. Patient outcome following standard dose radiotherapy or following a 12.5% increase in total dose to 75.6 Cobalt Gray Equivalent (CGE) using a conformal perineal proton boost was compared for local tumor control, disease-free survival, and overall survival. METHODS AND MATERIALS: Stage T3-T4, Nx, N0-2, M0 patients received 50.4 Gy by four-field photons and were randomized to receive either an additional 25.2 CGE by conformal protons (arm 1--the high dose arm, 103 patients, total dose 75.6 CGE) or an additional 16.8 Gy by photons (arm 2--the conventional dose arm, 99 patients, total dose 67.2 Gy). Actuarial overall survival (OS), disease-specific survival (DSS), total recurrence-free survival (TRFS), (clinically free, prostate specific antigen (PSA) less than 4ng/ml and a negative prostate rebiopsy, done in 38 patients without evidence of disease) and local control (digital rectal exam and rebiopsy negative) were evaluated. RESULTS: The protocol completion rate was 90% for arm 1 and 97% for arm 2. With a median follow-up of 61 months (range 3 to 139 months) 135 patients are alive and 67 have died, 20 from causes other than prostate cancer. We found no significant differences in OS, DSS, TRFS or local control between the two arms. Among those completing randomized treatment (93 in arm 1 and 96 in arm 2), the local control at 5 and 8 years for arm 1 is 92% and 77%, respectively and is 80% and 60%, respectively for arm 2 (p = .089) and there are no significant differences in OS, DSS, and TRFS. The local control for the 57 patients with poorly differentiated (Gleason 4 or 5 of 5) tumors at 5 and 8 years for arm 1 is 94% and 84% and is 64% and 19% on arm 2 (p = 0.0014). In patients whose digital rectal exam had normalized following treatment and underwent prostate rebiopsy there was a lower positive rebiopsy rate for arm 1 versus arm 2 patients (28 vs. 45%) and also for those with well and moderately differentiated tumors versus poorly differentiated tumors (32 and 50%). These differences were not statistically significant. Grade 1 and 2 rectal bleeding is higher (32 vs. 12%, p = 0.002) as may be urethral stricture (19 vs. 8%, p = 0.07) in the arm 1 versus arm 2. CONCLUSIONS: An increase in prostate tumor dose by external beam of 12.5% to 75.6 CGE by a conformal proton boost compared to a conventional dose of 67.2 Gy by a photon boost significantly improved local control only in patients with poorly differentiated tumors. It has increased late radiation sequelae, and as yet, has not increased overall survival, disease-specific survival, or total recurrence-free survival in any subgroup. These results have led us to test by a subsequent Phase III trial the potential beneficial effect on local control and disease-specific survival of a 12.5% increase in total dose relative to conventional dose in patients with T1, T2a, and T2b tumors.

Papillary and polypoid cystitis. A report of eight cases.

Eight patients from 20 months to 79 years of age (average, 49 years) with papillary or polypoid inflammatory lesions of the urinary bladder were studied. On cystoscopic examination or initial pathologic examination, several of the lesions were thought to be neoplasms. Their clinical and pathologic features, however, were typical for papillary and polypoid cystitis. Microscopic examination disclosed thin, finger-like papillae or broad-based polypoid lesions with prominent stromal edema typically associated with chronic inflammation. The lesions were covered by, and adjacent to, urothelium that was usually normal but was occasionally metaplastic. A history of recent catheterization was present in only one case. These cases illustrate that occasional papillary or polypoid urothelial lesions are inflammatory rather than neoplastic.

New and unusual aspects of ovarian germ cell tumors.

Ovarian germ cell tumors are reviewed with emphasis on recent developments. In the primitive germ cell tumor group the recently recognized subtypes of yolk sac tumor, the hepatoid and glandular variants are described. Hepatoid tumors, which resemble hepatocellular carcinomas, are usually admixed with other patterns of yolk sac neoplasia but when the hepatoid component predominates, distinction from metastatic hepatocellular carcinoma may be difficult. Glandular yolk sac tumors include those with a cribriform pattern as well as tumors that may be confused with endometrioid carcinoma. Within the teratoma category, a recent paper exploring the occasional relation between immature teratomas and dermoid cysts is reviewed. Problems caused by some of the monodermal teratomas are also highlighted. Struma ovarii may be the source of many diagnostic problems. It may be cystic and microscopic examination may reveal inconspicuous numbers of clearly recognizable thyroid follicles, resulting in confusion with other cystic ovarian tumors. In noncystic strumas many patterns, such as solid or pseudotubular, may be seen and the presence of cells with abundant clear or eosinophilic cytoplasm may add to the diagnostic difficulty, particularly if other teratomatous elements are lacking. Immunohistochemical staining for thyroglobulin may be crucial in establishing the diagnosis of a struma in these situations. The problem of identifying reliable criteria for malignancy of struma ovarii is explored on the basis of recent information. The two most recently recognized subtypes of carcinoid tumor, strumal and mucinous, are reviewed as are primary neuroectodermal and sebaceous tumors of the ovary. Unusual clinical features of germ cell tumors are discussed under three main categories: endocrine syndromes, paraendocrine and paraneoplastic syndromes, and miscellaneous. Included in these categories are disorders such as sexual precocity in association with germ cell tumors containing syncytiotrophoblast cells, endocrine abnormalities associated with the recently described functioning ovarian tumors with peripheral steroid cell proliferation, hyperthyroidism with struma ovarii, the carcinoid syndrome, autoimmune hemolytic anemia associated with dermoid cysts, complications of dermoid cyst rupture, which may simulate disseminated carcinomatosis, and ascites and Meigs' syndrome associated with struma ovarii.

Minimal-deviation endometrioid adenocarcinoma of the uterine cervix. A report of five cases of a distinctive neoplasm that may be misinterpreted as benign.

We describe five cervical adenocarcinomas with unusual, deceptively benign histological features that occurred in women 34 to 42 years of age and caused problems in interpretation. The tumors were incidental findings in hysterectomy or cone-biopsy specimens in four patients; the fifth patient was investigated because abnormal glandular cells were found on a Papanicolaou smear. One patient had been exposed in utero to diethylstilbestrol. The cervix is known to have been abnormal on gross evaluation in only one case. Microscopic examination disclosed a deceptively benign-appearing proliferation of glands and cysts for the most part unassociated with a stromal reaction. Cilia were present in four neoplasms and apical snouts in three. Features that indicated the neoplastic nature of the glandular proliferation in these cases, to varying extents in individual cases, included the number of glands and their distribution, the shapes of the glands, their presence deep in the cervical wall, the focal presence of a stromal reaction, and moderate cytologic atypicality with occasional mitotic figures. None of the tumors is known to have recurred or metastasized. In our opinion, these distinctive neoplasms represent minimal-deviation endometrioid adenocarcinomas of the cervix.

Malignant melanoma metastatic to the ovary. A clinicopathologic analysis of 20 cases.

Twenty cases of malignant melanoma metastatic to the ovary are reported. The patients, whose ages ranged from 21 to 60 (average 37.5) years, typically presented because of abdominal swelling or pain. Approximately 50% of the patients also had metastatic tumor outside the ovary, usually within the pelvis and upper abdomen, at the time of presentation. Twelve patients were known to have had a cutaneous malignant melanoma 1 month to 13 years before their ovarian tumors were discovered, and pigmented lesions had been removed previously from three other patients. Most patients are known to have died within a few years of discovery of their ovarian tumors but two were alive without evidence of disease 5 and 8 years later. The ovarian tumors, which were bilateral in nine cases, ranged up to 20 (average 10.5 cm) in greatest dimension. Six of them were either entirely black or had discernible black or brown foci. The most common microscopic appearance was that of large cells with abundant eosinophilic cytoplasm growing in nodular aggregates or diffusely. Occasional tumors were characterized by small cells with scanty cytoplasm, and in five tumors spindle cells were present. Another pattern was growth in the form of discrete rounded aggregates having a nevoid appearance. Eight tumors contained folliclelike spaces. Major cytologic features of the tumors included prominent nucleoli in 13, cytoplasmic pseudoinclusions in many nuclei in five, and intracytoplasmic melanin pigment in nine cases. In the 10 cases studied immunohistochemically, most of the tumor cells were strongly positive for S-100 protein and fewer cells were positive for HMB-45 in the seven tumors that were stained for this antigen. Melanosomes were identified in the three tumors examined ultrastructurally. These neoplasms often were difficult to differentiate from many other types of tumors, including juvenile granulosa cell tumor and small cell carcinoma, because of the presence of folliclelike spaces.

Nephrogenic adenoma. A report of 15 cases, review of the literature, and comparison with clear cell adenocarcinoma of the urinary tract.

The clinical and pathological features of 15 previously unreported and 98 reported cases of nephrogenic adenoma were reviewed and compared with those of the 19 reported clear cell adenocarcinomas of the urinary bladder and urethra. Nephrogenic adenoma has occurred in patients from 4 to 83 (average 41) years of age. Two thirds of the patients were male, and most had a history of a genitourinary operation or procedure, genitourinary trauma, urinary calculi, or a renal transplant. Nephrogenic adenomas are typically small but have measured up to 7 cm. They may be papillary, polypoid, or sessile, and approximately 18% have been multiple. Microscopic examination shows, singly or in combination, tubules, cysts, and papillae lined by cells that typically have scanty cytoplasm and exhibit little cytological atypia and no or only very rare mitotic figures. Clear cell adenocarcinomas, in contrast, occur in a generally older age group, have a strong predilection for females, and typically lack the clinical features associated with nephrogenic adenomas. The carcinomas are almost always solitary and usually large. The microscopic findings of a diffuse growth pattern, clear cells with a high cytoplasmic glycogen content, and significant nuclear atypia and mitotic activity are characteristic of carcinomas in contrast to nephrogenic adenomas.

Oxyphilic clear cell carcinoma of the ovary. A report of nine cases.

Nine clear cell carcinomas (CCC) of the ovary with a prominent component of cells with abundant eosinophilic cytoplasm are reported. The majority of these tumors--which we have designated "oxyphilic clear cell carcinomas"--were misinterpreted by the referring pathologists as tumors of other types. Each specimen, however, had one or more features establishing it as a clear cell carcinoma, including tubules and cysts lined by cuboidal, hobnail, or flattened cells; nests and sheets of cells with abundant clear cytoplasm containing glycogen; and an adjacent adenofibromatous component. Two tumors were bilateral. The ages of the patients (average, 55 years), their clinical presentation, and the gross appearance of the neoplasms were similar to those of clear cell carcinomas in general. The diagnosis of clear cell carcinoma should always be considered in the differential diagnosis of an ovarian tumor with oxyphil cells, particularly if the patient is postmenopausal. Thorough sampling should be undertaken in such cases to identify other, more typical foci of clear cell carcinoma in order to avoid misdiagnosis.

Florid cystic endosalpingiosis with tumor-like manifestations: a report of four cases including the first reported cases of transmural endosalpingiosis of the uterus.

Four cases of endosalpingiosis presenting as masses that resembled neoplasms are described in women 20, 41, 43, and 74 years of age. Each case was referred in consultation because of difficulties in pathologic diagnosis. In two patients, multiple cysts that involved the serosal surfaces of the uterus and adnexa in one case, and the colon, rectosigmoid, pelvic sidewalls, and the cul-de-sac in the other, were excised. In the other two cases, hysterectomy was performed for an enlarged cystic cervix in one case and presumed uterine leiomyomas in the other. In both of these cases, the uterine cervix and lower part of the uterine corpus were extensively involved by multiple cysts on gross examination, and in one of them, a frozen section of the cervical lesion was initially interpreted as "suspicious for invasive minimal deviation adenocarcinoma." On microscopic examination, benign endosalpingiotic glands and cysts were found in all four cases, with striking transmural involvement of the uterine cervix and lower uterine segment and contiguous corpus in the two cases with uterine involvement. The latter two cases are the first examples, to our knowledge, of endosalpingiosis involving the wall of the uterus; the differential diagnosis in these cases includes minimal deviation adenocarcinoma and florid tubal metaplasia with cystification. The four cases in this report, and rare previously reported cases, indicate that although usually a microscopic finding, endosalpingiosis can rarely present as a clinically or grossly evident mass that can be confused with a neoplasm.

Transitional cell neoplasms (carcinomas and inverted papillomas) of the uterine cervix. A report of five cases.

We report five transitional cell neoplasms of the uterine cervix: three infiltrating high-grade transitional cell carcinomas and two inverted transitional cell papillomas. The patients with TCCs were aged 34, 73, and 81 years, two presented with vaginal bleeding and the third with a large cystic ovarian mass. The three transitional cell carcinomas had a superficial noninvasive papillary component. Two tumors metastasized, one to the pelvic lymph nodes, the other to the ovary. The two patients with metastasis are alive after radical hysterectomy or total abdominal hysterectomy and chemotherapy, but follow-up is short. The third patient is currently receiving radiotherapy. Microscopically, the transitional cell carcinomas were similar to those originating in the urinary bladder or ovary. The inverted transitional cell papillomas were discovered in the cervixes of young adult women, one of whom had atypical squamous cells on a cervical smear at her presentation. The second patient had a slightly raised lesion in the cervix noted when routine smears were obtained. The microscopic features of the inverted transitional cell papillomas were similar to those of the corresponding tumor of the urinary bladder. It is important to separate transitional cell carcinomas from other papillary cancers of the cervix to delineate their clinical and pathological features and establish the prognostic differences, if any, from squamous cell carcinoma. Inverted transitional cell papilloma of the cervix represents a hitherto undescribed benign neoplasm arising at this site. These cases illustrate that cervical epithelium, which is known to undergo benign transitional cell metaplasia, may also give rise to benign and malignant transitional cell neoplasms.

Transitional cell carcinomas of the urinary bladder that may be underdiagnosed. A report of four invasive cases exemplifying the homology between neoplastic and non-neoplastic transitional cell lesions.

Four unusual invasive transitional carcinomas of the urinary bladder arose in patients aged 70 to 85 years. One or more specimens from each case were misinterpreted as benign. The features that led to diagnostic confusion included nests and trabeculae composed of cells with relatively bland cytologic features and small tubules, medium-sized glands, or cysts that suggested nephrogenic adenoma, cystitis glandularis, or cystitis cystica. In three cases, elongated slit-like lumens or clefts that frequently branched were also present, and several tumors had nests with pointed projections from which neoplastic cells invaded into the adjacent stroma in an often inconspicuous manner. In addition to their unusual patterns and frequent deceptive cytologic features, the tumors were noteworthy because they often had cells with abundant eosinophilic cytoplasm. A variety of architectural features, specifically a disorderly distribution of the epithelial elements, their frequent packed arrangement, and their variation in size and shape, all spoke for a neoplastic interpretation in the current cases. Additionally, in most of these cases, small clusters of cells or individual cells of more conventional invasive carcinoma facilitated the interpretation. The results of the study of these four cases expand the spectrum of recently described peculiar features of transitional cell carcinoma of the urinary bladder. Several of the findings in these tumors exemplify the parallels that exist between nonneoplastic epithelial abnormalities and transitional cell carcinoma of the bladder.

Florid cystitis glandularis of intestinal type with mucin extravasation: a mimic of adenocarcinoma.

Six florid examples of cystitis glandularis of intestinal type associated with focal mucin extravasation into the stroma are reported. Several of the cases caused major diagnostic difficulty with regard to their distinction from adenocarcinoma. Five patients had masses that simulated a bladder neoplasm. Patients ranged from 27 to 65 (average 46) years of age and complained of hematuria or irritative symptoms. Four patients were treated only by transurethral resection. One patient underwent partial cystectomy because of an erroneous diagnosis of adenocarcinoma and another total cystectomy because of a neurogenic bladder. Microscopic examination showed numerous glands lined by intestinal type epithelium, conforming to the appearance of the intestinal variant of cystitis glandularis. All cases had at least a minor component of typical cystitis glandularis, and it was prominent in four cases. All six cases had foci of basophilic mucin in the stroma, and this was prominent in four cases. Rounded aggregates of mucin were occasionally surrounded by compressed connective tissue cells, simulating mucinous cysts. In favour of a benign interpretation were the absence of epithelial cells in the extravasated mucin, the lack of atypicality of the cells lining the intestinal type glands in all but one case, a generally orderly distribution of the glands, and their lack of infiltration of the muscularis propria, although they abutted the latter in several cases. Follow-up from 2 to 14 years is available for three of the cases and has been uneventful, the longest follow-up being in the case diagnosed as adenocarcinoma. These cases illustrate the extent to which cystitis glandularis may mimic a neoplasm on gross evaluation and the propensity of mucin extravasation to cause diagnostic difficulty, a finding documented only rarely previously.

Serous adenocarcinoma of the uterus metastatic to the urinary bladder mimicking primary bladder neoplasia. A report of a case.

A 72-year-old woman with a history of transitional cell carcinoma of the urinary bladder was found to have a vesical neoplasm at cystoscopy. Microscopic examination of a biopsy specimen showed papillary adenocarcinoma. A subsequent endometrial biopsy, performed because of vaginal spotting, disclosed a serous papillary adenocarcinoma. A hysterectomy was performed. Pathologic examination showed that the tumor was deeply invasive of the myometrium. The uterine and bladder tumors were similar histologically. This case suggests that when examining a pure adenocarcinoma of the bladder, the pathologist should consider the possibility that it represents metastatic disease even in the absence of a known tumor elsewhere.

Endocervicosis of the urinary bladder. A report of six cases of a benign müllerian lesion that may mimic adenocarcinoma.

Six tumor-like glandular lesions characterized by a prominent component of endocervical-type epithelium involved the wall of the urinary bladder in women of reproductive age (31 to 44 years; mean, 37). All of the lesions posed problems in histologic diagnosis; indeed, a diagnosis of adenocarcinoma was initially rendered in three cases. Five patients presented with bladder symptoms, including--alone or in combination--suprapubic pain, dysuria, frequency, and hematuria. There was catamenial exacerbation of the symptoms in one case. The sixth patient--the only one with documented pelvic endometriosis--presented with dysmenorrhea, dyspareunia, and lower abdominal tenderness. In each patient, a mass that ranged from 2 to 5 cm in maximum dimension was typically located in the posterior wall or posterior dome of the urinary bladder. A partial cystectomy (five cases) or transurethral resection (one case) was performed. In one patient, extravesical pelvic soft tissue was involved, precluding complete resection of the lesion. Microscopic examination revealed extensive involvement of the bladder wall by irregularly disposed, benign-appearing, or mildly atypical endocervical-type glands, some of which were cystically dilated. Other findings included occasional ciliated cells, typically interspersed with the endocervical-type cells (four cases), a minor component of endometrioid glands (three cases), and glands lined by nonspecific cuboidal or flattened cells with eosinophilic cytoplasm (all cases). Some of the glands were surrounded only by the smooth muscle of the muscularis propria, but in other areas, the periglandular tissue was fibrous or edematous. In three cases, rare glands were surrounded by thin rims of endometriotic stroma. Gland rupture resulted in stromal extravasation of mucin in all cases and was a prominent feature in one. All patients had uneventful postoperative follow-up periods ranging from 1.5 to 14 years. The findings indicate that these bladder lesions are müllerian in nature and represent examples of endocervicosis, the mucinous analogue of endometriosis. Awareness of the lesion, which with one possible exception is hitherto undescribed in the bladder, and attention to its typical histologic features should facilitate its crucial distinction from adenocarcinoma.

Uterine carcinomas simulating microglandular hyperplasia. A report of six cases.

Six uterine adenocarcinomas, one cervical and five endometrial, that simulated microglandular hyperplasia histologically are described. The cervical neoplasm occurred in a 34-year-old woman who had been taking oral contraceptives. The five endometrial cancers occurred in postmenopausal patients 57 to 69 years of age; two of them were receiving, or had been receiving, premarin and provera and two were receiving only premarin. The patient with the cervical neoplasm had an abnormality observed on pelvic examination. The five postmenopausal patients presented because of vaginal spotting, bleeding, or discharge; their carcinomas were discovered in endometrial curettage specimens. On initial pathologic examination two specimens were misinterpreted as benign and in the remaining four cases there was uncertainty as to whether the lesion was benign or malignant. All the neoplasms had conspicuous microglandular patterns, with the gland lumens typically containing eosinophilic mucinous secretion and numerous acute inflammatory cells, which were also characteristically prominent in the stroma. Subsequent hysterectomies in all the cases showed residual adenocarcinoma with more typical features. Three of the endometrial tumors were mucinous adenocarcinomas and two mixed mucinous and endometrioid adenocarcinomas; the cervical tumor was a moderately differentiated adenocarcinoma of endocervical type. These cases illustrate that microglandular hyperplasia should be diagnosed with caution in a postmenopausal patient, particularly if lesional tissue is present in an endometrial curettage specimen, and, rarely, cervical adenocarcinomas have foci that simulate microglandular hyperplasia.

Metastatic intestinal carcinomas simulating primary ovarian clear cell carcinoma and secretory endometrioid carcinoma: a clinicopathologic and immunohistochemical study of five cases.

Five cases of ovarian metastases of intestinal adenocarcinomas that suggested the diagnosis of clear cell adenocarcinoma or the secretory variant of endometrioid carcinoma of the ovary are reported. Patient age ranged from 27 to 71 years at the time of diagnosis of the ovarian neoplasms. In four, the ovarian and intestinal tumors were discovered synchronously, and, in the fifth, the ovarian metastasis occurred 1 year after the intestinal primary was diagnosed. The ovarian tumors were unilateral in three patients and bilateral in two. They were up to 18 cm (mean, 12 cm) in maximum dimension and were characterized on microscopic evaluation by glands and cysts lined by cells whose most striking feature was abundant clear cytoplasm. In two cases, striking subnuclear or supranuclear vacuoles were present. An important clue to the diagnosis of metastatic intestinal adenocarcinoma was the presence in all cases of "dirty necrosis." The metastatic nature of the ovarian tumors was supported by the immunohistochemical findings. All tumors stained were strongly positive for carcinoembryonic antigen and cytokeratin 20 and failed to stain for CA125, whereas staining for HAM56 and cytokeratin 7 was absent or only focally positive in one case each. Three intestinal primary tumors involved the small bowel. Microscopic evaluation of the intestinal tumors in three cases and metastases in a fourth, in which the intestinal primary was not resected, showed the features of the uncommon clear cell variant of intestinal adenocarcinoma; the fifth was predominantly a conventional intestinal adenocarcinoma with only a focal clear cell component. Although intestinal adenocarcinomas metastatic in the ovary typically simulate endometrioid adenocarcinoma of the usual type or mucinous adenocarcinoma, they may mimic either primary clear cell adenocarcinoma or the secretory variant of endometrioid adenocarcinoma, particularly when the primary tumor is, even focally, the clear cell variant of intestinal adenocarcinoma.