Barbara-Christina Padberg

Immunocytochemistry in adrenocortical tumours: a clinicomorphological study of 72 neoplasms.

Surgical specimens of 72 adrenocortical tumours (ACTs) were investigated. Histologically, 57 tumours were classified as adenomas and 15 as carcinomas. In 9 of the latter cases, distant metastases and/or lethal outcome of disease was recorded. Immunocytochemistry showed only 2 ACTs to be positive for cytokeratin and 6 for vimentin. None of the 72 tumours showed argyrophilia or immunoreactivity for epithelial membrane antigen (EMA), S-100 protein, chromogranin A, Leu 7 or Leu-M1, while 31 cases exhibited positivity on inimunostaining with a polyclonal antiserum against synaptophysin. All 72 ACTs were immunoreactive with the recently described antibody D11. Thus the panel of antibodies described here could not discriminate between adenomas and carcinomas or between carcinomas with aggressive and indolent behaviour. Immunostaining with D11 and for EMA and Leu-M1 may help to distinguish ACTs from phenotypically similar lesions of different histogenesis.

DNA cytophotometry and prognosis in ovarian tumors of borderline malignancy. A clinicomorphologic study of 80 cases

Surgical specimens of 80 ovarian tumors of borderline malignancy (OTBM) were investigated by scanning DNA cytophotometry. Diploid or euploid DNA histograms were found for 21 tumors, whereas 59 OTBM showed noneuploid or aneuploid DNA patterns. All patients were followed‐up after surgery for at least 3 years (mean observation period, 6.7 years). Follow‐up showed 11 cases of recurrent disease and 6 deaths. DNA findings and several other morphologic and clinical details (including patient age, histologic type and stage of disease, and extent of therapy) were correlated to the postoperative course. Statistical analyses disclosed that, of these parameters, only DNA content significantly affected prognosis. Recurrences and deaths resulting from tumor exclusively were observed among patients with noneuploid or aneuploid OTBM, whereas none of the diploid or euploid tumors recurred (P < 0.05). DNA cytophotometry thus might be regarded as an effective complementary means to assess the prognosis of individual OTBM cases.

Adrenomedullary hyperplasia and phaeochromocytoma. DNA cytophotometric findings in 47 cases

Fifty adrenalectomy specimens containing normal (n=3), hyperplastic (n=4) or neoplastic (n=43) medullary tissue were subjected to quantitative cytophotometric measurements of DNA content. Differing evaluation schemes were applied for interpretation of DNA distribution patterns. Of the 43 phaeochromocytomas (PCC), 16 were inherited as part of the syndrome of multiple endocrine neoplasia type 2a (MEN 2a). Five of 27 sporadic PCCs followed a malignant course. Three benign and three malignant PCCs lacked endocrine activity. In normal medulla and in adrenomedullary hyperplasia, diploid or euploid DNA distributions were found. In contrast, 87% (33/38) of the benign and all 5 malignant PCCs exhibited non-diploid or aneuploid DNA histograms. No differences in DNA content existed between functioning and non-functioning PCCs or between sporadic and hereditary tumours. In this study, in contrast to earlier communications, DNA cytophotometry did not discriminate between benign and malignant adrenomedullary tumours. In addition, as opposed to the findings in a variety of other endocrine tumours, DNA measurements did not appear to be a useful tool to assess the prognosis of an individual malignant PCC.

Pathology of Sporadic and Hereditary Medullary Thyroid Carcinoma

Although cases of “malignant goitre with amyloid stroma” had already been described by the turn of this century in the German literature (Burk 1901; Jaquet 1906; Stoffel 1910), it is only 30 years since medullary carcinoma of the thyroid (MTC) was first clearly separated from the other types of thyroid carcinoma (Hazard et al. 1959). During the following decade, the classical histological features of MTC were described (Williams et al. 1966), the thyroid C-cell as the cell of origin delineated (Williams 1966), and the link with calcitonin (CT) production demonstrated (Cunliffe et al. 1968; Milhaud et al. 1968). It was, in addition, realized that a proportion of cases of MTC were genetically determined, occurring in association with phaeochromocytoma, or with phaeochromocytoma and multiple mucosal neuromas (Williams 1965; Schimke et al. 1968; Williams and Pollock 1966). Afterwards, the terms multiple endocrine neoplasia (MEN) 2 and MEN 3 were introduced by Steiner et al. (1968) and Khairi et al. (1975), respectively, to distinguish these combinations of tumours from Wermer’s syndrome (parathyroid, pituitary, and endocrine pancreatic tumours), which was given the name MEN 1 as it was described first. MEN 2 has been subsequently subdivided into MEN 2A (which includes MTC, phaeochromocytoma, and hyperparathyroidism) and MEN 2B (which refers to the neuromata syndrome including MTC, phaeochromocytoma, mucosal neuromata, gastrointestinal ganglioneuromatosis and marfanoid habitus) (Chong et al. 1975), and the term MEN 2B is now more commonly used than MEN 3 to designate the neuromata syndrome. The genetic defects leading to the development of familial MTC inherited in the setting of the MEN 2 syndromes are described in detail in R.F. Gagel et al., this volume. The aetiology and concrete pathogenesis of sporadic (non-hereditary) MTC has, in contrast, not yet been elucidated. It is, however, generally accepted that exogenous factors such as hypercalcaemia, hypervitaminoses D and A and irradiation known to be associated with higher incidence of MTC in various mammals are not carcinogenic to human C-cells (Saad et al. 1984a).

DNA-cytophotometry and immunocytochemistry in ovarian tumours of borderline malignancy and related peritoneal lesions

A total of 34 surgical specimens, obtained from 13 patients with ovarian tumours of borderline malignancy (OTBM), were investigated by conventional histology, immunocytochemistry and DNA cytophotometry. The lesions were obtained by primary ovarian surgery or second-look procedures and altogether comprised 19 (single and bilateral) OTBM, 8 cases of endosalpingiosis, 4 in situ and 2 invasive peritoneal implants and 1 overt adenocarcinoma. The morphological findings were related to follow-up data, which showed neoplasms with clinically malignant behaviour in 2 patients. The histology of the extra-ovarian manifestations was not associated with their immunocytochemical properties or with their DNA content. There were no correlations between the evolution of disease and microscopical features but the clinical course appeared to be linked to the DNA content of the extra-ovarian lesions, which was of greater prognostic importance than DNA ploidy of the ovarian tumours. Recurrence-free survival was noted in all 5 patients with diploid or euploid extra-ovarian proliferations, while the 2 clinically malignant cases fell into the group of 3 patients with noneuploid or aneuploid specimens. DNA estimations may be a methodology which increases the prognostic value of second-look procedures in OTBM patients.

Pathology of multiple endocrine neoplasias 2A and 2B: a review.

This review describes recent findings on the morphology, function and prognosis of lesions associated with the MEN 2 syndromes. Special emphasis is placed on the analogies and discrepancies between the hereditary and nonhereditary manifestations of the endocrine proliferations involved.

DNA cytophotometry in adrenocortical tumours: A clinicomorphological study of 66 cases

Surgical specimens of 66 adrenocortical tumours were investigated by conventional microscopy and DNA cytophotometry. Histologically, 50 neoplasms were classified as adenomas and 16 as carcinomas. In only 8 of the latter cases were distant metastases and/or a lethal outcome recorded. On single cell scanning cytophotometry either non-euploid or aneuploid DNA histograms were identified in 24 of 50 adenomas (48%) and in 14 of 16 carcinomas (88%). The two carcinomas exhibiting euploid DNA distributions fell into the group of 7 malignancies which are recurrence-free so far. From these findings it is concluded that DNA measurements have no diagnostic and only limited prognostic value in neoplasms of the adrenal cortex.