Epithelial peroxidase and endometrial granulocytes in the normal cyclic human endometrium.

Studies in animal models have clearly shown a relationship between the administration of estrogens and the appearance of peroxidase activity in growth-responsive estrogen target tissues (endometrium, cervix, vagina, breast, and DMBA rat mammary tumor). We have studied the ultrastructural localization of endogenous peroxidase activity in the normal cyclic human endometrium. Endogenous peroxidase activity was not identified in proliferative phase endometria, with the exception of one very late proliferative phase endometrium. Most secretory phase endometria showed at least some ultrastructurally identified peroxidase activity in glandular epithelial cells. The number of epithelial cells showing peroxidase activity varied from less than 10% to 85%. The peroxidase activity was present throughout the endoplasmic reticulum of these epithelial cells, extending from the perinuclear cistern to the most peripheral portions of the endoplasmic reticulum adjacent to the apical lumen. Biochemical assays of peroxidase activity in these endometria were compared with the ultrastructurally identified epithelial peroxidase and the endometrial granulocyte count. Uterine granulocyte peroxidase appeared to make a substantial contribution to the total peroxidase activity assayed by biochemical methods. Standard biochemical techniques alone, therefore were not considered to be adequate to evaluate epithelial peroxidase activity.

Cellular differentiation in ovarian sex-cord-stromal and germ-cell tumors studied with antibodies to intermediate-filament proteins.

Seventy ovarian sex-cord-stromal and germ-cell tumors were immunohistochemically studied for the presence of intermediate-filament proteins of different types used as markers for cellular differentiation. Cells of ovarian granulosa-cell tumors constantly expressed vimentin and appeared to lack cytokeratin. Two tumors previously classified as granulosa-cell tumors were reclassified as poorly differentiated "common" epithelial tumors based on their cytokeratin positivity, vimentin negativity, and morphologic features. Dysgerminomas and Leydig-cell tumors showed only vimentin positivity. Tubular structures in androblastomas, which are considered to represent Sertoli-cell differentiation, were cytokeratin positive, and thus differed from the majority of normal Sertoli cells that are known to express vimentin and not cytokeratin. Embryonal carcinomas, choriocarcinomas, and endodermal sinus tumors showed cytokeratin positivity in the neoplastic cells whereas vimentin was observed in the stromal cells. In immature teratomas, epithelial differentiation was demonstrated with cytokeratin antibodies, and neural and glial differentiation was also frequently demonstrated by immunostaining with antibodies to neurofilaments and glial fibrillary acidic protein. The results show that antibodies to intermediate filaments can be used in the differential diagnosis between ovarian epithelial and nonepithelial tumors, and they provide a very accurate additional method to characterize the cellular differentiation of ovarian neoplasms.

Diffuse malignant peritoneal mesothelioma in a 13-year-old girl. Report of a case and review of the literature.

A case of diffuse malignant peritoneal mesothelioma in a 13-year-old girl is described. The patient had a short history of abdominal pain, distention, and tenderness. At laparotomy she was found to have ascites and numerous nodules and plaques affecting the peritoneal cavity and the omentum. A diagnosis of diffuse pseudotumoral deciduosis was made, which on review was revised to malignant peritoneal mesothelioma. The patient's condition gradually deteriorated and she died 8 months after diagnosis in spite of administration of combination chemotherapy.

Giant multilocular prostatic cystadenoma: a distinctive lesion of the retroperitoneum in men. A report of two cases.

Two examples of large, multiloculated, cystic tumors that arose within the pelvis in men of 28 and 37 years of age are described. The tumors were composed of glands and cysts lined by prostatic-type epithelium lying in a hypocellular fibrous stroma. The prostatic nature of the lesions was confirmed by immunohistochemical staining of the epithelium for prostate-specific antigen and prostatic acid phosphatase. Two apparently similar lesions were found in the literature; one tumor was attached to the prostate by a pedicle, and the other arose in the retrovesical space. These tumors, for which we propose the designation "giant multilocular prostatic cystadenoma," appear to be benign, although they may recur if incompletely excised. They may pose considerable diagnostic difficulty if the prostatic nature of the epithelium is not appreciated, an error that is likely if a relationship to the prostate is not recognized. This lesion should be included in the differential diagnosis of retroperitoneal cystic tumors in men.

Ovarian mucinous carcinoids including some with a carcinomatous component: a report of 17 cases.

Only rare primary mucinous (goblet cell) carcinoids of the ovary have been reported, and their clinicopathologic features have not been well delineated. The authors studied 17 examples from patients 14 to 74 years of age. The clinical presentations were similar to those of ovarian neoplasms in general. The tumors ranged from 0.8 to 30 cm in diameter. In six cases the tumor was in the wall of a mature cystic teratoma, appearing grossly as solid nodules or areas of thickening in four of them, six tumors were entirely solid, and five were solid associated with other types of cystic tumor. The tumors were divided into three groups on the basis of their microscopic features. Six neoplasms, designated "well differentiated," were composed of small glands, many of which floated in pools of mucin. The glands were lined by goblet cells and columnar cells, some of which were of neuroendocrine type. Three tumors, designated "atypical," were characterized by crowded glands, some of which were confluent, small islands with a cribriform pattern, and scattered microcystic glands. The glands were lined by cuboidal to columnar cells, some of them neuroendocrine, admixed with goblet cells. Eight tumors, designated "carcinoma arising in mucinous carcinoid," contained islands and larger nodules of tumor cells, or closely packed glands, as well as single cells, mainly of the signet ring cell type. Most of the cells were devoid of mucin and were severely atypical with marked mitotic activity. Necrosis was present in all eight tumors. Seven of the eight tumors with a carcinomatous component contained at least minor foci of well-differentiated mucinous carcinoid; the eighth contained only foci of atypical mucinous carcinoid. The neuroendocrine nature of a variable proportion of the cells in all three groups was demonstrated by staining for neuroendocrine markers. The mucinous nature of other cells was confirmed by mucicarmine or Alcian blue stains. The ovary contained an intrinsic component of trabecular and insular carcinoid, and of strumal carcinoid in one case each, an adjacent mature cystic teratoma in six cases, mucinous cystadenocarcinoma in three cases, and borderline mucinous cystic tumor, borderline Brenner tumor, and epidermoid cyst in one case each. Fifteen tumors were stage I, one was stage II, and one was stage III. The last two tumors had a carcinomatous component. Follow-up data were available for 15 patients; 12 were alive and free of tumor 2.3 to 14 years (average, 4.7 years) after the ovarian tumor was excised. One patient, whose tumor had a carcinomatous component, died 3 years postoperatively of unrelated causes. Two patients, both of whom had a carcinomatous component in their tumor, died 9 and 12 months postoperatively. Primary mucinous carcinoids must be distinguished from metastatic mucinous carcinoid tumors from the appendix or elsewhere. Features supporting an ovarian origin are the additional presence in the specimen of teratoma or an ovarian surface epithelial tumor, an absence of blood vessel or lymphatic space invasion, and confinement to a single ovary. Similar features help to distinguish mucinous carcinoids from Krukenberg tumors. Mucinous carcinoids should also be distinguished from strumal carcinoids, which can contain mucinous glands, and insular carcinoid tumors that arise rarely in the wall of a mucinous cystic neoplasm. Although the number of cases in this series is small, the follow-up data suggest that the degree of differentiation, particularly the presence of frank carcinoma, is an important prognostic factor.

Large cell calcifying Sertoli cell tumor of the testis: contrasting features of six malignant and six benign tumors and a review of the literature.

We report six malignant and six benign large cell calcifying Sertoli cell tumors of the testis and compare the features of malignant and benign cases based on these cases and those in the literature. All the tumors in this report consisted of sheets, nests, solid tubules, and cords of eosinophilic cells, with focal calcifications, as well as a substantial neutrophilic infiltrate in 11 of them. Analysis of our cases and those in the literature showed that the malignant tumors were unilateral and solitary and occurred at a mean age of 39 years (range 28-51 years), whereas the benign neoplasms were bilateral and multifocal in 28% of cases and occurred at a mean age of 17 years (range 2-38 years). Only one malignant tumor occurred in a patient with evidence of a genetic syndrome (Carney syndrome), whereas 36% of benign tumors had various genetic syndromes or endocrine abnormalities. Most of the tumors in the latter cases were bilateral and multifocal. There were strong associations of malignant behavior with size >4 cm, extratesticular growth, gross or microscopic necrosis, high-grade cytologic atypia, vascular space invasion, and mitotic rate greater than three mitoses per 10 high-power fields. All malignant cases exhibited at least two of these features, whereas all benign cases lacked any of them. The presence of any one of these features in a solitary large cell calcifying Sertoli cell tumor, especially in a patient >25 years of age, should be viewed as suspicious for malignant behavior, whereas the presence of two or more of these features indicates a strong probability of a malignant course. "Low" percentages (< or =35%) of tumor cells staining for proliferating cell nuclear antigen (PCNA) also may correlate with benign behavior, but some benign tumors have high PCNA values. Ki-67 values (MIB-1 antibody) did not correlate with biologic behavior, nor did immunostains for p53 protein.

Germ cell neoplasms of head and neck soft tissues: a pathologic spectrum of teratomatous and endodermal sinus tumors.

Germ-cell neoplasms, in particular teratomas with immature and mature somatic type tissues, are some of the most commonly found tumors in children. Approximately 5% of these neoplasms appear in one of several extracranial sites in the head and neck region. This study reports the clinical, pathologic and immunohistochemical findings in six germ-cell neoplasms occurring in the neck and facial areas. A mass was recognized at birth in five children, and the sixth patient was 2 1/2 years old at diagnosis. Four of the six neoplasms contained one or another element of endodermal sinus tumor; two of these had a mixed pattern of endodermal sinus tumor and teratoma. The other two cases were purely teratomas. The serum alpha-fetoprotein was known to be elevated in three children whose tumors had endodermal sinus elements; it returned to normal level in two of the children, but remained high in the one fatal case. Placental alkaline phosphatase and alpha-fetoprotein were demonstrated immunohistochemically in two of the three cases, with available tissue containing endodermal sinus tumor. Teratomatous metastases in ipsilateral cervical lymph nodes were found in one patient with a pure teratoma; that patient is disease-free one year after surgery. Only nine previous examples of endodermal sinus tumor have been reported in the head and neck region, exclusive of the central nervous system. There is one other case in the literature of a congenital cervicothyroidal teratoma with metastatic disease. These six neoplasms illustrate the clinical and pathologic spectrum in this nosologically homogeneous, but morphologically diverse, category of tumors.

Poorly differentiated (small cell) carcinoma of the ovary in young women: evidence supporting a germ cell origin.

The clinical and pathologic features, including immunohistochemistry and electron microscopy, of six cases of poorly differentiated carcinoma of the ovary (small cell carcinoma) are presented. These tumors occurred in six young patients ranging in age from 10 to 24 years. Two patients had hypercalcemia. All tumors were unilateral, and four patients had advanced stage disease at presentation. Histologic features included sheets, nests, and cords of cells in a fibrous stroma, focal microcysts, and a dimorphic population of small and large cells. Eosinophilic, hyaline globules occurred in five cases, intercellular basement membrane-like substance in two cases, and glycogen in all cases. Five of six cases stained strongly for cytokeratin and vimentin; intracytoplasmic laminin was identified in three cases; and three cases were believed to show faint positivity for alpha-1-antitrypsin. Stains for alpha-fetoprotein were negative. Ultrastructural examination of two cases showed granular material in dilated rough endoplasmic reticulum, intermediate filaments, intracytoplasmic dense globules, maculae adherens, and extracellular basement membrane-like material. All of the cases proved rapidly fatal despite various therapies, as did a histologically similar testicular tumor that was admixed with seminoma and teratoma. We interpret these findings to indicate that this ovarian cancer is most likely of germ cell origin, and it may be related to yolk sac tumor, although it is clearly distinct from the classical yolk sac tumor.

Aggressive uterine sarcoma with rhabdoid features: diagnosis by peritoneal fluid cytology and absence of INI1 gene mutation.

We report a primary uterine sarcoma with classic histologic, immunohistochemical, and ultrastructural features of a malignant extrarenal rhabdoid tumor (MERT). It arose in a 71-year-old woman who presented with postmenopausal bleeding, ascites, and a right pelvic mass. Malignant cells with rhabdoid morphology were identified by cytologic examination of the peritoneal fluid. Exploratory laparotomy revealed a 10-cm right adnexal mass and disseminated peritoneal tumor. Pathologic study showed diffuse expansion of the endometrial stroma by rhabdoid-like cells with transmural infiltration of the myometrium and extensive involvement of uterine serosa and right ovary by tumor. Neoplastic cells were immunoreactive for vimentin, cytokeratin, and epithelial membrane antigen, and cytoplasmic whorls of intermediate filaments were observed by electron microscopy. Fluorescence in situ hybridization (FISH) studies with chromosome 22-specific probes showed no loss of the INI1 gene, and no coding sequence mutation was identified.

Carcinoid tumors of the ovary.

Carcinoid tumors of the ovary are uncommon, but 150 cases of primary ovarian carcinoids and 40 cases of carcinoid tumors metastatic to the ovary have been reported. Primary carcinoid tumors of the ovary are divided into insular, trabecular, strumal and mucinous types. The insular type is most common, followed by the strumal type. The majority of primary ovarian carcinoids occur in association with mature cystic teratoma, but a considerable number present in pure form. Only the insular type is associated with the carcinoid syndrome. The age incidence of patients with ovarian carcinoids shows a wide range but most patients are postmenopausal. Primary carcinoids of the ovary are invariably unilateral. They form a solid nodule within a cystic teratoma, or when pure a solid yellow-grey mass, and vary from microscopical to large tumors measuring in excess of 20 cm in the longest diameter. The metastatic carcinoids are nearly always bilateral and scattered tumor deposits are present throughout both ovaries. Primary ovarian carcinoids metastasize only occasionally, and should be treated as ovarian tumors of low malignant potential.

Spermatocytic seminoma associated with rhabdomyosarcoma.

A case of spermatocytic seminoma intimately associated with rhabdomyosarcoma is reported. The patient, a 51-year-old man, presented with a two-year history of right-sided testicular enlargement. Orchiectomy was performed, and a large testicular tumor was excised. Further investigations during hospitalization revealed lung, liver, and retroperitoneal lymph node metastases. Further therapy was refused, and the patient died at home two months after orchiectomy. Autopsy was not permitted. Although the great majority of spermatocytic seminomas occur in pure form, do not metastasize, and have very good prognosis, in addition to the present case, seven cases of spermatocytic seminoma associated either with rhabdomyosarcoma or undifferentiated sarcoma have been reported. Presence of the sarcomatous element is associated with aggressive behavior, metastatic disease, and very poor prognosis. It is considered that the sarcomatous element develops from the spermatocytic seminoma by anaplastic transformation.

Alpha-lactalbumin in "common" epithelial tumors of the ovary. An immunohistochemical study.

Alpha-lactalbumin (AL) has been widely used as an immunohistochemical marker for mammary carcinoma. The authors have investigated the AL reactivity of 36 unselected ovarian epithelial neoplasms using the avidin-biotin-peroxidase immunoperoxidase technic. In eight serous cystadenocarcinomas, both the primary neoplasm and its metastases were examined. Of the 36 tumors, 7 (19.4%) showed positive staining for AL and 5 were of the serous type. The serous tumors showed moderate to strong staining reaction. Three serous cystadenocarcinomas were AL positive in both primary and metastatic sites, while the remaining five were negative in all sites. One mucinous cystadenoma and one clear cell carcinoma showed weak to moderately positive AL reactivity. There was no good correlation between AL positivity and the presence of malignancy or between AL positivity and tumor grade. In view of the relatively high AL reactivity in ovarian neoplasms, it is advisable to exercise caution in interpreting the presence of AL positivity as specific marker for mammary carcinoma.

Villous adenoma arising in Meckel's diverticulum.

The first well documented case of villous adenoma arising in a Meckel's diverticulum not associated with a carcinoma is reported. A 21 year old man with long history of medically treated ulcerative colitis was admitted to hospital with severe pain and bleeding. Total abdominal colectomy and ileo-anal anastomosis was performed and during this procedure Meckel's diverticulum containing a villous adenoma showing minimal dysplasia was found and resected. The diverticulum was lined partly by ileal and partly by gastric epithelium, and the villous adenoma originated from the gastric mucosa.

Hepatic fibrosis in a child possibly due to prolonged methotrexate.

A case is described in which marked hepatic fibrosis probably resulted from the prolonged treatment of acute leukaemia with methotrexate.

Immunoglobulins in Jamaicans and Nigerians with immunogenetic typing of myeloma and lymphoma in Jamaicans.

Serum IgG concentration was lower in Jamaicans than in Nigerians. The maternalfoetal IgG ratio was also lower in Jamaican sera than in Nigerian sera. It is suggested that endemic malaria in Nigeria may be responsible for these differences. The higher IgM concentration in the Nigerian cord sera may be further evidence of this. Eighteen new cases of myeloma were detected in Jamaicans between August 1966 and May 1967. Based on Gm typing, only two of these showed evidence of mixed white ancestry. All the others had the typical Gm groups of Negroes. Similarly, only two patients out of a total of 17 with malignant lymphoma showed evidence of mixed white ancestry. Twelve of the patients with myeloma showed serum proteins of the IgG type, five were IgA, and one had only light chains in the serum. The majority of the patients had myeloma protein of the kappa type. The Gm typing suggested that six patients had myeloma protein of the gamma1 heavy chain subclass, and one patient had a gamma3 subclass heavy chain, the remainder belonging most likely to the gamma2 heavy chain subclass since gamma2 occurs about four times as frequently as gamma4.

Morphometric data to FIGO stage and histological type and grade for prognosis of ovarian tumours.

The prognostic value of using histological typing, grading, and morphology, in addition to clinical staging, was assessed in 98 cases of invasive ovarian cancer of the common epithelial types (serous, mucinous, and endometrial). All of these cases had at least five years of follow up. When regression analysis was used, the International Federation of Gynaecology and Obstetrics' (FIGO) staging system was the best indicator for prognosis. Analysis of a combination of morphometric features was the second best indicator, being especially useful for the those patients with stage I disease. Variables that indicated a relatively poor prognostic outcome were mitotic index above 30; volume percentage epithelium above 65%; shortest nuclear axis above a mean of 1 X 1 micrometers. Histological typing of ovarian tumours was of limited value; mucinous tumours have a somewhat better prognosis than serous tumours, but the prognostic value of typing alone was found to be limited. Qualitative histological grading was useful, but the prognostic value of morphometric grading was better. Measurement of morphological features with an interactive computer program is simple and can be done by a pathologist or a technician: in future it is likely that such automated systems of measurement will improve the objectivity of tissue analysis.

Granular cell tumor of the breast mimicking carcinoma in pregnancy.

A granular cell tumor of the breast in a 20-year-old black pregnant woman is reported. Malignancy had been suspected clinically, radiologically, and on gross pathologic examination. Frozen section provided the correct diagnosis and the lesion was excised, obviating more radical surgery.

Pseudosarcoma botyroides in pregnancy: report of a case with ultrastructural observations.

A case of pseudosarcoma botryoides of the vagina diagnosed in advanced pregnancy is described. The cellular characteristics (atypical cells and abnormal mitoses) suggested malignancy, but ultrastructural studies demonstrated the fibroblastic nature of the cells, thus confirming the diagnosis of pseudosarcoma. Local excision and subsequent cesarean section was the method of treatment. Three years later, another pregnancy was terminated by repeat cesarean section and uncontrollable hemorrhage requiring emergency hysterectomy. The histologic study of the bleeding area revealed very edematous areas and lacunaelike endothelium-lined vessels. No cellular abnormalities were observed.

Analysis of chromosome aneuploidy in ovarian dysgerminoma by flow cytometry and fluorescence in situ hybridization.

We determined the DNA ploidy and the centromeric copy number of chromosomes 7, 12, 18, and X in four cases of ovarian dysgerminoma using DNA flow cytometry and fluorescence in situ hybridization (FISH) with chromosome-specific alpha-satellite probes. The analyses were performed on nuclei isolated from paraffin-embedded tissue. The DNA index of the tumors ranged from 1.75 to 2.08 (near tetraploid). The FISH analysis demonstrated five copies of chromosome 7 and four copies of chromosome 12 in most tumors. The copy number of chromosome 18 ranged from two to four. The X chromosome was present in three copies in most tumors. These data show that the aneuploidy profile of dysgerminoma is similar to that of testicular seminoma. Overrepresentation of chromosomes 7 and 12 and under-representation of chromosome 18 are characteristic cytogenetic features of seminoma. Seminoma and dysgerminoma share the same chromosomal marker, an isochromosome i(12p). Our data suggest that these tumors are also characterized by a similar, nonrandom pattern of chromosome gains and losses.

Primary carcinoid tumor of testis.

A case of pure, primary testicular carcinoid tumor in a forty-four-year-old male is reported. The patient presented with painless testicular enlargement, and testicular tumor was diagnosed. Orchiectomy was performed, and histology revealed a primary argentaffinoma. The patient is well and symptom free two years after diagnosis.