Mesonephric adenocarcinomas of the uterine cervix: a study of 11 cases with immunohistochemical findings.

Mesonephric adenocarcinoma is a rare variant of cervical carcinoma with relatively few, well-documented cases reported. We describe the clinicopathologic and immunohistochemical features of 11 examples of this neoplasm, which occurred in women between the ages of 35 and 72 years (mean, 52 years). Most (64%) patients had abnormal vaginal bleeding. Eight tumors were stage IB, and one each was stage IIB and IVB; in one, the stage was unknown. Microscopically, the carcinomas showed various morphologies, most commonly a small tubular pattern or a ductal pattern resembling endometrioid adenocarcinoma; one tumor had an associated malignant spindle cell component. Ten neoplasms were adjacent to hyperplastic mesonephric remnants. Follow-up in 10 cases showed six patients to be alive without evidence of recurrence after a mean of 4.8 years. The patients with stage IIB and IVB disease had local recurrences after 2.2 and 0.7 years and died of progressive disease at 3.2 and 0.8 years, respectively. In a patient with stage IB disease, a mediastinal metastasis and a malignant pleural effusion developed 5.6 years after diagnosis, and the patient died of disease at 6.2 years. Another patient with stage IB disease and a positive vaginal cuff margin that recurred locally after 1.7 years received chemotherapy and was alive and clinically free of disease at 2.5 years. Mesonephric adenocarcinomas were immunoreactive for epithelial markers (AE1/3; CK1, CAM 5.2, cytokeratin 7, and epithelial membrane antigen) (100%), calretinin (88%), vimentin (70%), androgen receptor (33%), and inhibin (30%, focal staining). No immunostaining was detected with cytokeratin 20, estrogen receptor, progesterone receptor, and monoclonal carcinoembryonic antigen. This staining profile is similar to that of mesonephric remnants and may be useful in the distinction of mesonephric carcinoma from mullerian endometrioid adenocarcinoma, with which it may be confused.

Malignant mesonephric neoplasms of the uterine cervix. A report of eight cases, including four with a malignant spindle cell component.

Eight mesonephric adenocarcinomas of the uterine cervix, four of which had a malignant spindle-cell component, occurred in women aged 34 to 71 (median 43, mean 54.5) years, bringing to 14 the number of cervical mesonephric carcinomas in the literature. The tumors with a malignant spindle-cell component ("malignant mesonephric mixed tumors") are, with one possible exception, the first reported examples at this site. The patients, almost all of whom presented with vaginal bleeding, underwent hysterectomy; five also had a pelvic lymph node dissection. The tumors were all stage IB, although microscopic lymph node metastases were found in two cases. Gross examination revealed an invasive cervical mass in each case. On microscopic examination, seven tumors were adjacent to mesonephric hyperplasia, which in five cases was florid and focally atypical; in the remaining case, occasional non-neoplastic mesonephric tubules were found only within the tumor. The adenocarcinomas typically exhibited a variety of patterns, including a ductal pattern resembling endometrioid adenocarcinoma, a small tubular pattern, a retiform pattern, a solid pattern, and a sex-cord-like pattern. These disparate patterns frequently caused diagnostic difficulty. The spindle-cell component generally resembled endometrial stromal sarcoma or a nonspecific spindle-cell sarcoma; one tumor also contained multiple foci of osteosarcoma and another, a single chondroid focus. Immunohistochemical staining for a variety of antigens failed to reveal a distinctive profile, although all the carcinomas were immunoreactive for vimentin. Follow-up in six cases revealed three patients to be alive without evidence of recurrence at postoperative intervals of 2 to 3 years. Recurrent tumor developed in a fourth patient 1 year after hysterectomy; she was treated with chemotherapy and was alive and free of disease at 2 years. Another patient had intra-abdominal recurrences (including liver metastases) at 9 and 11 years and was alive with tumor at 13 years. Death at 8.5 months in a final patient was probably due to an independent stage IIc ovarian clear-cell carcinoma. These and prior observations in the literature suggest that malignant mesonephric tumors of the cervix may be more indolent than their müllerian counterparts, from which they should be distinguished. Mesonephric carcinomas in this site should also be distinguished from florid mesonephric hyperplasia, with which they are usually associated.

Immunohistochemical type distinction of alpha-fetoprotein in various alpha-fetoprotein-secreting tumors.

In order to clarify the histogenesis of alpha-fetoprotein (AFP)-secreting tumor tissues, formalin-fixed, paraffin-embedded serial sections of 148 tumors in various organs were examined by the peroxidase-antiperoxidase method for AFP, and paradoxical concanavalin A staining. Yolk sac-type AFP was found in yolk sac tumors, embryonal carcinomas, solid teratomas, (yolk sac) endodermal cell tumors, adenocarcinomas (stomach, ovary or lung) and metastatic liver cancers. Hepatic-type AFP was demonstrated in hepatocellular carcinomas, hepatoblastomas, solid teratomas and a stomach cancer. Yolk sac-type AFP was observed in the neighboring liver cells of metastatic liver cancers without relation to the type of AFP in primary cancers. The results from serum analyses of preoperative tumor-bearing patients (68 cases) were coincident with those from immunohistochemical stainings.

Analysis of a non-ras 21-kDa protein in patients with metastatic testicular germ-cell tumors.

A novel protein of 21 kDa (p21) has been detected in the sera of patients with different solid tumors. The serum levels of this p21 protein were measured in seven patients with metastatic testicular germ-cell tumors before and after chemotherapy using an enzyme-linked immunosorbent assay. In five out of six patients who responded to chemotherapy a concomitant decrease of p21 serum levels was found. The decrease of p21 was in accordance with the decline of the established tumor markers alpha-fetoprotein, human chorionic gonadotropin beta-subunit and lactate dehydrogenase in three patients with non-seminomatous tumors and with the decline of lactate dehydrogenase and the clinical response in two patients with seminoma. In one patient the predicted decline of p21 did not occur despite the patient's clinical response to chemotherapy. In the seventh patient, who relapsed directly after chemotherapy, no decline of either p21 levels or tumor markers was observed. The absolute amount of the p21 protein prior to chemotherapy did not correlate with the patients' tumor burden. Elevated levels of p21 were found in patients with seminomatous and non-seminomatous germ-cell tumors. Since seminoma patients do not secrete tumor markers like alpha-fetoprotein or human chorionic gonadotropin beta, the determination of p21 levels may help to evaluate the efficacy of chemotherapy in patients with seminomatous as well as in patients with marker-negative non-seminomatous germ-cell tumors. The biological role of p21 and its clinical significance will be further investigated.

Evidence for the transformation of seminoma to yolk sac tumor, with histogenetic considerations.

Recent ultrastructural, cytogenetic, and ploidy analyses indicate that seminoma acts as a precursor from which other forms of testicular germ cell tumor may originate. Ten cases of primary or metastatic testicular germ cell tumors were investigated that showed possible transformation of seminoma to yolk sac tumor. Such transformation was identified in six cases in which foci of abrupt change from seminoma to various patterns of yolk sac tumor occurred, often at the periphery of otherwise pure lobules of seminoma. Immunostains for cytokeratins, placental-like alkaline phosphatase, and alpha-fetoprotein demonstrated the expected changes in reactivity at the foci of such transformation. Four additional cases were regarded as either seminomas with artifactual microcystic change or the close association of seminoma and yolk sac tumor but lacking evidence for transformation. These data support the theory that seminoma is not an "endpoint" neoplasm but may serve a precursor role in the progression to nonseminomatous germ cell tumors.

Morphology and immunohistochemistry of carcinoma in situ adjacent to testicular germ cell tumours in adults and children: implications for histogenesis.

Observations differ on the pre-invasive malignant lesions associated with the various categories of testicular germ cell tumours. Such lesions have been found to be similar in appearance and are assumed to be composed of multipotent cells, or conversely a distinctive pre-invasive stage has been reported in association with each form of germ cell neoplasm. This study was undertaken to see whether distinctive morphological and immunohistochemical features of carcinoma in situ adjacent to various categories of germ cell tumours could be established. Carcinoma in situ adjacent to seminomas, teratomas and mixed germ cell tumours in 18 adults was indistinguishable morphologically. Placental alkaline phosphatase was demonstrated immunohistochemically but vimentin and low molecular weight cytokeratins were uniformly absent in these abnormal germ cells from all three groups. These findings support the concept of a multipotent pre-invasive malignant cell for both seminoma and teratoma in the adult. Carcinoma in situ was not seen adjacent to 15 spermatocytic seminomas, nor was placental alkaline phosphatase demonstrated in tubules adjacent to these tumours. These negative findings are additional evidence that spermatocytic seminoma differs from classical seminoma in its histogenesis. Carcinoma in situ, as defined morphologically and immunohistochemically in adults, was not identified adjacent to yolk sac tumours and differentiated teratomas in 20 prepubertal testes. The possibility that pre-invasive malignancy in children may not resemble that in adults must be considered when assessing the malignant potential of cryptorchid testes on biopsies taken during orchidopexy.

Pulmonary blastoma with germ cell (yolk sac) differentiation: report of two cases.

Pulmonary blastoma is a rare lung neoplasm of disputed histogenesis and variable biologic behavior. Typical cases contain both epithelial and mesenchymal tissues, and a variety of patterns of differentiation have been described. While expression of oncofetal antigens in these tumors has been noted rarely, a coexisting component of germ cell tumor has not been reported previously. We describe the clinical and pathologic features of two cases of pulmonary blastoma having alpha-fetoprotein production and histologic areas of yolk sac tumor. We also report the finding of immunohistochemical staining of fetal lung tissue for alpha-fetoprotein.

p53 protein alterations in human testicular cancer including pre-invasive intratubular germ-cell neoplasia.

Expression of the p53 oncoprotein was examined in a wide range of primary human testicular germ-cell tumours using a new mouse monoclonal antibody (MAb) BP53-11 raised and characterized in this study, in parallel with a polyclonal rabbit antiserum CM-1. Immunohistochemistry on paraffin sections showed positive nuclear reaction in at least a fraction of malignant cells in 90 (84%) out of 107 cases studied. Aberrant accumulation of the p53 protein was found among testicular tumours of all major histological types, although generally a higher percentage of positive cases and a higher proportion of p53 over-expressing nuclei within individual lesions was observed in embryonal carcinomas when compared with seminomas. The typical heterogeneous staining pattern characteristic of histological specimens was also found in a cultured cell line derived from a human embryonal carcinoma. In contrast to immunohistochemically undetectable levels in normal testes and morphologically normal tissue areas in the tumour-bearing testes, the accumulation of the p53 protein was clearly identified in a high proportion (59% of cases) of the pre-invasive lesions with positive atypical intratubular germ cells often found in the tissue adjacent to invasive tumours. Altered expression of the p53 protein is therefore a unifying feature of the majority of invasive male germ-cell tumours and the change resulting in high levels of p53 appears to be a relatively early step in the human testicular cancer pathogenesis.

Yolk sac tumor of the liver.

A primary yolk sac tumor of the liver in a 16-mo female is presented. The fine needle aspiration biopsy (FNAB) cytology of this lesion is illustrated and discussed. This case supports continued exploration of the use of FNAB in childhood abdominal masses.

[Features of the histogenesis of testicular yolk sac tumors in children]. / Osobennosti gistogeneza opukholi zheltochnogo meshka iaichek u detei.

32 cases of a yolk sac tumour of the testis in children aged up to 5 years underwent retrospective morphological study. Foci of proliferation of activated gonocytes identical to the type A spermatogonia with clear nuclei and the type B spermatogonia characterized by a negative PAS-reaction and reaction to alpha-fetoprotein are observed in the seminiferous tubules surrounding a tumour. Besides this areas of the primordial germinogen cell generation are found among the cells lining the system of labyrinths and channels of the yolk sac tumour. A new hypothesis of the yolk sac tumour histogenesis in the child testis is put forward--namely, through the transformation of the activated gonocytes in the seminiferous tubules into their "somatic" phase, i.e. into the yolk sac elements from which they originate. Likewise, the scheme is suggested reflecting a cyclic character of the germinogenic cells in ontogenesis. This scheme allows visual representation of the process of the parthenogenetic development of germinogenic tumours.