Biomedical subjects
Publications and source records attributed to R E Scully.
Steroid-hormone-producing ovarian tumors include those in which the neoplastic cells secrete hormones as well as a wide variety of tumors in which the neoplastic cells stimulate the ovarian stroma or adjacent hilus cells to become hormonally active.
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BACKGROUND: Endometrial squamous cell carcinoma is extremely rare, with only 56 cases reported in the literature. METHODS: Six cases of endometrial squamous cell carcinoma were found in a review of 1182 cases of uterine corpus cancer treated at the Massachusetts General Hospital from 1975 to 1993. Two additional cases were seen in pathological consultation. The clinicopathological features of these 8 cases and the 56 reported cases were analyzed. RESULTS: The average age of the patients was 67 years; almost all of them were postmenopausal. The most frequent presenting symptom was vaginal bleeding. Chronic pyometra and nulliparity were predisposing factors. The average duration of symptoms before diagnosis was 11.5 months. Total abdominal hysterectomy with bilateral salpingo-oophorectomy was the primary treatment in 58 patients. Eighty percent of the patients with Stage I tumors survived; the median follow-up time was 32 months. The survival rate for patients with Stage III tumors was only 20%, and all 6 patients with Stage IV disease died. CONCLUSIONS: The preoperative diagnosis of endometrial squamous cell carcinoma may be difficult, since curettage specimens may show only highly differentiated squamous epithelium. The strong relationship between tumor stage and survival suggests that early diagnosis and treatment are imperative.
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Twenty-six endometrioid adenocarcinomas of the fallopian tube that occurred in patients 37 to 85 (average 57) years of age are described. Most of the patients presented with symptoms related to a pelvic mass but nine tumors were incidental findings at the time of operation. All the neoplasms were unilateral. Eighteen tumors were Stage I, four Stage II, two Stage III, and two Stage IV. Two tumors were primary in the fimbriated end of the tube. On gross examination the typical appearance was that of a fusiform swelling of the tube which contained a predominantly intraluminal neoplasm up to 6 cm in greatest dimension. Six separate tumors were present in one case. Microscopic examination revealed that 14 tumors were typical endometrioid carcinomas with foci of squamous differentiation in 7 cases, spindle cells interpreted as epithelial cells in 4 cases, and a trabecular pattern in 1 case. One of these 14 tumors was composed almost exclusively of oxyphilic cells lining glands. Twelve tumors were characterized by a mostly solid proliferation of small closely packed cells punctured by numerous glands that varied from small to cystic, imparting a superficial resemblance to an adnexal tumor of probable Wolffian origin. Benign stromal osseous metaplasia was noted in two Wolffian-like and one typical endometrioid carcinoma. Five tumors were grade 1, 11 were grade 2, and 10 were grade 3. Follow-up information was available for 18 patients. Five with noninvasive Stage Ia-0 tumors (intraluminal, noninvasive masses) were without disease at 2 to 5 (average 3) years postoperatively. Two of three patients with Stage Ia1 tumors were alive without recurrence at 2 and 3 years postoperatively. One of two patients with Stage Ia2 disease for whom follow-up is available was alive without disease 1.5 years postoperatively and one died of other causes 11.2 years postoperatively. One patient with Stage Ic disease had recurrence of tumor at 2 years; four with Stage II disease were without disease at 1.5, 2, 3, and 8 years; one with Stage IIIa disease died with disease at 4 years; and one with Stage IV disease died with disease after 5 years. Two additional patients had fimbrial tumors [Stage I(f)]; one of them died with disease at 7 years, and the other was alive without disease at 8 years. This small series indicates that endometrioid carcinomas of the fallopian tube are characteristically noninvasive or only superficially invasive and have a generally favorable prognosis. This subtype of tubal carcinoma should be distinguished from the more common neoplasms of serous type and from those of various other cell types.
The clinical and pathological features of 25 smooth-muscle tumors of the vulva were analyzed. The patients ranged in age from 17 to 67 (mean, 37.6) years; two were pregnant. Twenty-three tumors were 1.5 to 16 (mean, 5.2) cm in greatest dimension; the size of two tumors was unknown. Microscopic examination showed that 16 tumors were circumscribed, six had focally infiltrative margins, and the margins could not be evaluated in three tumors. Fourteen tumors were composed mainly of spindle cells; two of these tumors had prominent myxoid stroma. Seven tumors were predominantly epithelioid and had a prominent hyalinized or myxoid stroma; often the cells had a plexiform pattern. Four tumors contained an approximately equal number of epithelioid and spindle cells. Ten tumors had mild, nine moderate, and six severe cytologic atypia. Mitotic figures ranged from 0 to 10 (average, 1.8) per 10 high-power fields (hpf). Immunohistochemically, all the tumors stained for one or more muscle markers. Thirteen of 17 tumors were positive for estrogen receptors, and 16 of 18 were positive for progesterone receptors. Follow-up information ranging from 1 month to 19 years (average, 5 years) was available in 19 cases. Four tumors recurred locally, and one patient with recurrent tumor died of metastases 7 months after the initial operation. We propose an expanded criteria to distinguish between leiomyomas and leiomyosarcomas of the vulva. Tumors that manifest three or all of the four following features should be considered sarcomas: > or = 5 cm in greatest dimension, infiltrative margins, > or = 5 mitotic figures per 10 hpf, and moderate to severe cytologic atypia. Those that have only one of these characteristics should be diagnosed as leiomyoma, and those that exhibit only two of these features should be considered benign but atypical leiomyomas. The sarcomas should be excised with widely negative margins; the leiomyomas and the atypical leiomyomas should be excised conservatively, with long-term, careful follow-up.
A total of 37 cases of ovarian primary squamous cell carcinoma (SCC)-19 associated with a dermoid cyst (SCCD), seven associated with endometriosis (SCCE), and 11 pure (SCCP)-are described. The last 18 cases belong within the new World Health Organization category of SCC in the surface epithelial-stromal category. The 19 patients with SCCD were 21-75 (mean, 52) years old; three of the carcinomas were in situ and seven, six, and three tumors were stages I, II, and III, respectively. The tumors and associated dermoid cysts were 6-35 cm in greatest dimension, usually forming mural nodules with intracavitary protrusion and focal necrosis and hemorrhage; two, seven, and seven tumors were grades 1, 2, and 3, respectively. SCCD was focally associated with a columnar epithelial cyst lining in 13 cases, suggesting an origin therein. One patient with stage I, grade 1 SCCD also had squamous cell carcinoma in situ (CIS) of the cervix. The seven patients with SCCE were 29-70 (mean, 49) years old, and one, three, one, and two tumors were stages I, II, III, and IV, respectively; all of the tumors were grade 3. One was associated with squamous cell carcinoma in situ of the cervix. The 11 patients with SCCP were 27-73 (mean, 56) years old, and one, four, five, and one tumors were stages I, II, III, and IV, respectively. The tumors were 6-26 cm in greatest diameter, usually solid with focal necrosis; one and 10 tumors were grades 2 and 3, respectively. Three patients with SCCP also had cervical squamous cell carcinoma in situ. The patients with SCCE had a poorer overall survival than those with SCCD. Five of the six patients with SCCE for whom adequate follow-up information was available died of their disease (mean survival, 5 months); also, in all five cases of SCCE reported in the literature, the patients died of their disease (mean survival, 4 months). The stage of the tumor and its grade correlated best with overall survival for all three types of SCC.
Nine cases of malignant mesothelioma (MM) presenting as ovarian masses occurred in female patients aged 16 to 63 (median, 52) years. In most of the cases, the referring pathologist initially misdiagnosed the neoplasm or was uncertain about its nature. In two cases, the tumors were confined to one or both ovaries, representing primary ovarian MMs; only one similar case has been previously reported. In the other cases, widespread peritoneal tumor precluded definite conclusions about the primary or secondary nature of the ovarian involvement. That at least some of the latter were also primary ovarian MMs is suggested by a degree of ovarian enlargement, the striking parenchymal replacement, or both, which are not usually seen in cases of secondary ovarian involvement by peritoneal MMs. The clinical presentation was usually that of abdominal or pelvic pain or abdominal swelling, an adnexal mass on pelvic examination or at laparotomy, or combinations thereof. One tumor was an autopsy finding. There was no history of asbestos exposure in any patient. Eight patients underwent bilateral oophorectomy, usually with hysterectomy and biopsies of extraovarian tumor. Four patients were given chemotherapy and one, radiation therapy. Follow-up in five cases revealed that three patients had died of tumor at postoperative intervals of 8 to 44 months, one was alive with persistent tumor at 18 months, and one was alive with no clinical evidence of tumor at 11 years. The ovaries were replaced by tumors 3 to 15 cm in maximum diameter; seven were bilateral. The neoplastic tissue was typically solid, but small cysts were present in two cases, and one tumor was a unilocular cyst with a solid mural nodule. On microscopic examination, tumor involved both the serosa and the parenchyma of the ovary in seven cases, the serosa only in one case, and the parenchyma only in one case. Seven tumors were exclusively epithelial, with papillary, tubular-glandular, and solid patterns, and two were biphasic. The cells in the epithelial mesotheliomas usually exhibited moderate atypicality and a low mitotic rate. The stroma was typically hyalinized, and in three of the cases with a papillary pattern papillae with hyalinized cores were a striking finding. Psammoma bodies were present in three cases. Histochemical and immunohistochemical stains confirmed the mesothelial nature of the tumor cells. Because of the wide variety of microscopic patterns in MMs, the differential diagnosis of ovarian MM includes a variety of primary and metastatic ovarian tumors as well as other peritoneal mesothelial lesions.
Five patients with ovarian endometrioid tumors composed predominantly of ciliated cells are reported; two patients had bilateral neoplasms. Two unilateral, predominantly cystic ciliated-cell tumors from women in their 40s were associated with endometriosis: one was borderline and arose in an endometriotic cyst; the other was borderline with foci of carcinoma and was associated with ipsilateral ovarian and peritoneal endometriosis. Five predominantly adenofibromatous tumors in the three other women, all postmenopausal, were not associated with endometriosis. One woman with a borderline ciliated-cell adenofibroma had had a prior contralateral adnexectomy, another with a borderline ciliated-cell adenofibroma had a contralateral ciliated-cell adenofibroma, and the third woman had a ciliated-cell adenocarcinoma and a contralateral borderline ciliated-cell adenofibroma. In two of the latter three patients the fallopian tubes contained foci of ciliated-cell hyperplasia. All five ciliated-cell malignant tumors were stage I, were treated by operation alone, and had not recurred 21 to 64 (mean 39) months postoperatively. Ciliated-cell tumors of the ovary should be distinguished from serous and mixed serous and endometrioid cancers because of different pathological and possibly different clinical features. Criteria for separating endometrioid ciliated-cell tumors into benign, borderline, and malignant categories are presented; whether any of these neoplasms behaves in a clinically aggressive fashion has yet to be determined.
Five primary ovarian carcinomas composed of a high-grade neuroendocrine tumor of non-small-cell type and a surface-epithelial-stromal tumor are reported. The five tumors presented in women aged 36 to 77 (mean, 57) years with abdominal distension or a palpable mass in three cases, right lower quadrant pain with tenderness and fever in one case, and a cervicovaginal smear showing a high estrogen effect in one postmenopausal patient. The tumors were unilateral, 9 to 30 (mean, 16) cm in greatest dimension, and had solid and cystic components. Three tumors were stage I; one, stage II; and one, stage III. Two patients who received chemotherapy died of tumor 8 and 36 months postoperatively, another who refused chemotherapy but later received radiation died of tumor after 19 months, a fourth was lost to follow-up, and a fifth was treated recently. Microscopically, the neuroendocrine components of all the tumors were composed predominantly of sheets, closely packed islands, cords, and trabeculae of epithelial cells with little intervening stroma. The tumor cells in the neuroendocrine areas were medium-sized to large compared with the cells of small cell carcinoma, and they contained scanty to moderate amounts of cytoplasm and hyperchromatic nuclei with coarse chromatin clumping in three cases and abundant cytoplasm and vesicular nuclei with single, large eosinophilic nucleoli in the other two. In all the cases, areas of necrosis and single-cell necrosis were extensive, and mitotic figures were abundant. Positive argyrophil and argentaffin reactions were observed in occasional to many cells in all cases. The glandular components of the tumors were grade 1/3 endometrioid adenocarcinoma (one case), grade 2/3 mucinous adenocarcinoma (2 cases), and mucinous borderline tumor with small foci of mucinous adenocarcinoma (two cases). Numerous enterochromaffin cells were identified in hematoxylin and eosin sections of the borderline mucinous components of two tumors; occasional nonargentaffin argyrophilic cells were present in the endometrioid and mucinous carcinoma components. Luteinized stromal cells were present focally in two cases, including the case in which there was evidence of a high estrogen level. Immunohistochemical studies in five cases showed staining of most cells in the solid components for cytokeratin and chromogranin A and some to most cells for serotonin and neuron-specific enolase. Neuropeptides that were detected in the solid component of one or more of the cases included vasoactive intestinal peptide, somatostatin, gastrin, and glucagon; negative results were obtained for pancreatic polypeptide and insulin. Flow cytometry in four tumors revealed that the neuroendocrine component was aneuploid in two, suspicious for aneuploidy in one, and diploid in one. Tumors of the type described are distinct pathologically from primary ovarian carcinoid tumors and small cell carcinoma of pulmonary type. Although experience with this type of tumor is limited, the prognosis appears to be poor.
PURPOSE: The initial management of stage I nonHodgkin's lymphoma of the testis is by orchiectomy but the role and efficacy of adjuvant strategies are uncertain. We reviewed cases of lymphoma at our institution to determine whether adjuvant treatment was beneficial. MATERIALS AND METHODS: A retrospective review of outcome was conducted on 26 patients who presented to our institution. Median followup for the group was 54 months. Kaplan-Meier actuarial analyses were performed on the entire group and subsets. RESULTS; Actuarial 5 and 10-year overall survival rates were 79% and 63% and relapse-free survival rates were 61% and 46%, respectively. In patients who received adjuvant combination chemotherapy the 5-year relapse-free survival rate improved (75% versus 50%) but effect did not achieve statistical significance and was lost by 10 years. No relapse-free survival advantage was noted for patients receiving adjuvant irradiation to the pelvic and para-aortic nodes. Patients who did not receive irradiation remained free of isolated relapses in the pelvic or para-aortic regions. CONCLUSIONS: These data lend support to the use of adjuvant chemotherapy but do not support a role for adjuvant nodal irradiation.
The clonality of disseminated serous carcinoma involving the ovary, peritoneum, and, occasionally, the endometrium is controversial. Histopathologic examination alone cannot unequivocally distinguish between a monoclonal origin and a multicentric origin. Two patients with peritoneal serous carcinoma with minimal ovarian involvement (one with endometrial serous carcinoma), nine patients with stage III bilateral ovarian carcinoma, and one patient with stage III bilateral carcinosarcoma were studied for clonality. One patient with ovarian carcinoma that recurred after chemotherapy was also studied. Previous analyses of single frozen tumor specimens from these patients had identified different p53 gene mutations in each patient. To test the hypothesis that the disseminated cancers had a monoclonal origin, we assayed DNA from numerous foci from each patient to determine whether the known p53 mutation was present in each specimen. Identical mutations were detected in the tumor foci from each patient with peritoneal dissemination and minimal ovarian involvement, including one patient with an endometrial serous carcinoma as well. In all the patients with bilateral ovarian cancer, the genetic change in p53 was identical in both ovarian tumors. Genetic progression was observed in two patients, one of whom showed a loss of heterozygosity involving the p53 gene in a recurrent tumor. In the second patient, a p53 mutation not present in either ovarian tumor was detected in a metastatic tumor from the omentum. These results strongly suggest that disseminated serous carcinomas, whether primary in the ovary, endometrium, or peritoneum, are of monoclonal rather than multicentric origin; that bilateral stage III ovarian cancers are typically of monoclonal origin; and that additional genetic events involving p53 might occur during progression of these tumors.
Ten benign biphasic cervical tumors that we have designated "adenomyomas of endocervical type" are reported because they might be confused with adenocarcinoma. The patients ranged from 21 to 55 years of age (mean, 40 yr). Two presented with abnormal vaginal bleeding, but, in most patients, the cervical tumors did not cause symptoms. On physical examination or at operation, eight patients were found to have tumors ranging from 1.3 to 8.0 cm in greatest dimension growing into the endocervical canal and, in three cases, prolapsing through the external os. The remaining two patients had mural tumors measuring 11.0 and 23.0 cm in greatest dimension, which projected into the pelvis from the outer aspect of the cervix, without mucosal involvement. The tumors were well circumscribed and grey-white or tawny, and five contained multiple mucin-filled cysts up to 3.0 cm in diameter. One tumor was focally hemorrhagic. On microscopic examination, the tumors were composed of glands and cysts lined by a single layer of endocervical-type mucinous epithelium admixed with smooth muscle. The epithelial component was typically composed of large irregularly shaped glands with papillary epithelial infolding, surrounded by smaller simple glands, frequently resulting in a lobular arrangement. Tubal-type epithelium was present focally in six tumors and endometrial-type glands surrounded by endometrial stroma were present in one case. Both the epithelium and smooth muscle were uniformly bland, without significant mitotic activity. Five patients were treated initially by "polypectomy." Hysterectomy 1 month and 1 year later in two of the cases revealed residual adenomyoma; a "recurrence" 3 years after polypectomy in another patient was treated by hysterectomy. In no case has there been evidence of spread beyond the cervix. The finding of a cervical tumor composed of bland, irregularly shaped, mucinous glands surrounded by smooth muscle caused significant problems in differential diagnosis and a diagnosis of adenoma malignum was either favored or raised as a possibility by the initial pathologist in five of the cases. The gross circumscription of the adenomyomas, their polypoid appearance, the frequent lobular arrangement of glands, the absence of invasive glands with a desmoplastic stromal reaction, and lack of even focal atypia were the most helpful findings in differentiating these tumors from adenoma malignum.
Nine vulvar and three vaginal angiomyofibroblastomas from patients 23 to 71 years of age (mean, 46 yr) were analyzed. The tumors were well circumscribed and ranged from 0.9 to 11 cm (average, 4.7 cm) in maximal dimension. On microscopic examination, they had hypercellular and hypocellular areas. The neoplastic cells were spindle-shaped, plasmacytoid, or epithelioid; a variable number were binucleated or multinucleated cells. A focal storiform pattern was present in one tumor, and, in one tumor, the neoplastic cells formed a collar around a central area of dense collagen. There was no significant nuclear atypia, and there was less than one mitotic figure per 10 high-power fields. The tumors contained small- to medium-sized blood vessels, which were characteristically thin walled and, occasionally, ectatic and branching. The stroma was edematous, separated collagen fibers and contained a variable number of inflammatory cells, especially lymphocytes and mast cells. Three vulvar tumors contained a variable amount of fat. Ultrastructural study of three tumors showed intracytoplasmic, dilated, rough endoplasmic reticulum, moderate numbers of pinocytotic vesicles, and numerous filaments without dense bodies; rare intercellular rudimentary junctions were identified. Eleven of 11 tumors were immunoreactive for vimentin, 11 of 12 for desmin, three of 11 for muscle actin, one of 12 for smooth muscle actin, and four of 12 for CD34. There was no staining for factor XIIIa, keratin, S100 protein, Leu-7, glial fibrillary acidic protein, or CD68. Follow-up revealed no recurrences or metastases. Angiomyofibroblastoma is a distinctive benign tumor that arises most commonly in the vulva and vagina and has a diverse histologic and immunohistochemical profile.
Two cases of hyperplastic mesothelial cells within intra-abdominal lymph nodes were encountered in staging procedures in a 59-year-old woman with bilateral ovarian serous borderline tumors and in a 21-year-old woman with a Sertoli-Leydig cell tumor of intermediate differentiation. Both patients also had mesothelial hyperplasia of the pelvic and abdominal peritoneum; in one of them, the hyperplasia was striking. The intranodal mesothelial cells occupied the sinusoids of the lymph nodes and were initially suspected of being metastatic from the ovarian tumor in each case. The appearance of the cells on routine stains suggested the correct diagnosis, which was confirmed by histochemical and immunohistochemical staining. These cases represent the first reported examples of mesothelial cells within abdominal lymph nodes, although similar involvement of mediastinal lymph nodes has been described in three patients with pleural effusions. Intranodal mesothelial cells should be distinguished from metastatic tumor, an error that could result in inaccurate staging in a patient with a known tumor or prompt a futile search for an occult primary tumor. Moreover, it is important that in studies evaluating the frequency of nodal involvement by serous borderline tumors, intranodal mesothelial cells should not be misinterpreted as metastatic borderline tumor, a distinction that can be difficult with only routinely stained sections.
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We report two cases of synovial sarcoma arising in the vulva. The patients were 30 and 37 years old and presented with a painless mass that was interpreted clinically as a cyst. The tumors were 2.0 and 1.2 cm in greatest diameter. Histologically, they were composed of epithelial cells forming solid nests and gland-like and papillary structures surrounded by spindle-shaped cells. Immunohistochemically, the epithelial cells stained for cytokeratin and the spindle-shaped cells for vimentin. Ultrastructurally, the epithelial cells had prominent intercellular junctions and narrow microvilli and were separated from the spindle-shaped cells by a basal lamina. The spindle-shaped cells were closely apposed with focal intercellular contacts. One tumor recurred locally 3.5 years after excision, but the patient was alive and well 1 year after a re-excision and radiation therapy. The other patient was alive and well 4 years after an excision. These tumors are the first reported examples of synovial sarcoma arising in the vulva.
Ninety percent of ovarian cancers in the Western world are epithelial cancers derived from the surface epithelium of the ovary and its inclusion cysts. The so-called surface epithelium is mesothelium that comes to resemble epithelium as it is reflected over the surfaces of the ovaries. At various ages, but particularly in women in the reproductive, menopausal, and postmenopausal age groups, this epithelium migrates into the ovarian stroma to form inclusion cysts. These cysts probably results from a dynamic interplay of surface epithelium and underlying ovarian stroma, but can also develop as a result of periovarian adhesions. There is abundant evidence that their formation is not related to repair of ovulation. It is generally accepted that benign and malignant ovarian epithelial tumors arise from surface epithelium and its cystic derivatives because they both, but particularly the latter, have a potential to differentiate into epithelia similar to those of normal müllerian derivation (tubal, endometrial, and endocervical epithelia) and their tumors resemble those of the fallopian tube, endometrium, and endocervix. Also, both intraepithelial carcinomas and precarcinomatous lesions can be observed in the surface epithelium and its cystic derivatives. These carcinomas may arise de novo or as a transformation of pre-existing benign tumors and non-neoplastic lesions of similar derivation. Surface epithelial inclusion cysts have a greater propensity to undergo neoplasia than does the surface epithelium itself. This difference has been recognized for many years most epithelial ovarian tumors are intraparenchymal, rather than being located on the ovarian surface. More recent evidence includes the immunohistochemical demonstration of various ovarian carcinoma antigens far more frequently in inclusion cyst epithelium than in surface epithelium; and the much more frequent presence of tubal metaplasia in the cyst epithelium than in the surface epithelium. Tubal metaplasia is encountered in non-neoplastic ovaries contralateral to ovarian carcinomas two to three times as frequently as in control ovaries, suggesting that the metaplastic epithelium is more prone to the development of carcinoma that non-metaplastic epithelium. Carcinoma precursors occur in the ovary, as in the cervix and endometrium, but have been reported only rarely because they are easily overlooked and have not been searched for by pathologists.