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SAVONAROLA The Rise and Fall Of a Renaissance Prophet By Donald Weinstein Yale University Press. 400p $38 Girolamo Savonarola's life spanned the latter half of the 15th century, at a [...]

Background. Small cell carcinomas (SCC) are the most common ovarian tumors associated with hypercalcemia. Parathyroid hormone-related protein (PTHrp) is the most frequent cause of hypercalcemia of malignancy. Methods. The presence of PTHrp in SCC has been studied by immunohistochemistry in formalin fixed, paraffin embedded tissues. A polyclonal antibody against a synthetic peptide corresponding to the first 36-N terminal amino acid residues of PTHrp was used. Normal dog skin, which is rich in PTHrp, was used as a positive control. Absorption tests using the synthetic peptide as antigen were done in all the cases. Results. Immunoreactivity for PTHrp was found in five of seven cases of SCC. The serum calcium levels were elevated in two of these cases, normal in two, and unknown in one. The two negative cases were associated with high serum calcium levels. Conclusion. The lack of correlation between immunoreactivity and serum calcium levels can be explained on the basis that immunohistochemistry is dependent on the peptide content of cells rather than on the capability for hormone production and/or release. The results suggest that PTHrp plays a role in the development of hypercalcemia in patients with SCC of the ovary. Cancer 1994; 73:1878-81. Key words: small cell carcinoma, ovary, hypercalcemia, parathyroid hormone-related protein, immunohistochemistry.

Background. The search for methods of early detection of ovarian carcinoma in recent years has emphasized the lack of information regarding the histologic features of early carcinoma or its precursor lesions; few examples of early de novo ovarian carcinoma have been reported. Methods. The clinicopathologic features of 14 cases of early ovarian carcinoma detected as microscopic findings in grossly normal ovaries retrieved from a consultation practice and the files of the Massachusetts General Hospital were reviewed. Results. The patients ranged in age from 27-65 years (mean, 50 years). Three women had a family history of ovarian carcinoma and six did not. The tumors ranged from microscopic to 7 mm in greatest dimension; all were unilateral and four were multifocal. One tumor involved the surface and its crypts; four, the surface and superficial cortex; eight, the superficial cortex only; and in one, surface involvement was not ascertainable. Ten carcinomas were serous; one, endometrioid; one, clear cell; and two, poorly differentiated, of undetermined cell type. Severe atypia of the noncarcinomatous surface epithelium or its inclusion cysts was additionally present in three cases. Among the seven patients whose diagnoses were made at the time of oophorectomy who had follow-up data of at least 2 years or until recurrence or death, five were alive without recurrences, one was alive with recurrence, and one died of tumor. Two of the three women died whose ovarian tumors were diagnosed retrospectively on discovery of subsequent peritoneal carcinomatosis, and the third was alive with recurrent tumor. No relation between any clinical or pathologic feature and survival was apparent in this small series except for a suggestion that well differentiated tumors had a good prognosis. Conclusions. These findings document that at least a subset of ovarian epithelial cancers develops de novo. The guarded prognosis associated with these tumors despite their minute dimensions raises questions about the value of current screening techniques for early detection of ovarian cancer. Cancer 1994; 73:1859-64. Key words: ovarian neoplasms, early carcinoma, de novo carcinoma, ovarian intraepithelial neoplasia.

Twelve cases of ovarian metastases from cervical carcinomas, most with clinical manifestations of ovarian involvement, are reported. The patients were 23-73 years of age (average, 43 years). The ovarian and cervical tumors were synchronous in eight patients; in three, ovarian tumors were discovered 10 months, 2.5, and 3 years after the detection of a cervical neoplasm. In one patient, the cervical tumor was not discovered until autopsy 7 months after presentation. Four patients had abdominal swelling or distention, three had vaginal bleeding, three had an abnormal Papanicolaou smear, and two had masses discovered during pelvic examination. The ovarian tumors, six of which were bilateral, ranged from 5-17 cm (average, 9.5 cm) in maximal dimension in 11 patients; in the 12th patient, the involved ovary was not enlarged. The cervical tumors were grossly evident in 10 patients. They were usually deeply invasive, often with extracervical extension. Four were squamous cell carcinomas; two, small cell carcinomas; one, a mixed small cell carcinoma and adenocarcinoma; one, a mixed poorly differentiated carcinoid and adenocarcinoma; two, adenosquamous carcinomas; one, a transitional cell carcinoma; and one, an undifferentiated carcinoma. Various features, including bilaterality of the ovarian tumors, the finding that the histologic features of the ovarian tumors typically were unusual for a primary ovarian neoplasm, and the presence of extensive extracervical disease, led to the conclusion that the ovarian tumors were metastatic from the cervix. Although ovarian metastases of cervical carcinoma are uncommon, this series illustrates that, occasionally striking examples with clinical manifestations of ovarian involvement occur. Cancer 1993; 71:407-18.

Seven small cell carcinomas of extragenital and extra-pulmonary origin that metastasized to the ovary are described. The tumors occurred in women who were 21-77 years of age (mean, 49 years) and were discovered at, or close to, the time of presentation. The primary sites were the intestine (three cases), thymus (two cases), and inguinal skin (one case), and in one case it was undetermined. The ovarian tumors, four of which were bilateral, ranged from 1.2 to 25 cm in diameter (mean, 11 cm). Microscopic examination showed typical features of small (oat) cell carcinoma in six cases; one neoplasm resembled a small cell carcinoma of intermediate cell type and contained rare glands. On immunohistochemical examination, six of six tumors stained for cytokeratin, five of five for neuron-specific enolase, two of six for chromogranin, and none of four for vimentin. The primary cutaneous tumor was a Merkel cell carcinoma. The patient with that case died at 8 months. Two patients with intestinal tumors died at 1 and 2 months, and one is free of disease at 4 years after receiving chemotherapy. Both patients with mediastinal tumors received chemotherapy; one died at 11 months and one had brain metastases at 5 months and was lost to follow-up. The final case is recent. The differential diagnoses in these cases include primary ovarian small cell carcinomas of hypercalcemic and pulmonary types and various other small cell malignant tumors metastatic to the ovary. Consideration of a variety of clinical and pathologic features should enable these important distinctions to be made. Cancer 1993; 71:177-86.

THE ROMANOVS 1613-1918 By Simon Sebag Montefiore Alfred A. Knopf. 784p $35 In popular lore, the impression that most likely comes to mind regarding the Romanovs is one of failure: [...]