Inhibin and CD99 (MIC2) expression in uterine stromal neoplasms with sex-cord-like elements.

Uterine mesenchymal neoplasms with sex-cord-like elements are designated as endometrial stromal tumor with sex-cord-like elements (ESTSCLE) or uterine tumor resembling ovarian sex-cord tumor (UTROSCT), depending on the extent of sex-cord-like differentiation. Occasionally, sex-cord elements similar to those in ESTSCLE and UTROSCT occur in uterine adenosarcomas. To determine whether the sex-cord-like elements in these tumors show immunohistological evidence of sex-cord differentiation, we studied a series of uterine neoplasms for expression of inhibin, a peptide hormone expressed by normal ovarian granulosa cells and ovarian sex-cord neoplasms, and CD99, a protein also expressed by granulosa cells, Sertoli cells, and some ovarian sex-cord tumors. Thirty uterine mesenchymal neoplasms (five epithelioid or plexiform smooth muscle tumors, three endometrial stromal tumors, two mixed endometrial stromal and smooth muscle tumors, 10 ESTSCLE, five UTROSCT, and five miscellaneous stromal processes) and five epithelial neoplasms were evaluated for expression of CD99 (clone 12E7) and inhibin (clone R1) in formalin-fixed, paraffin-embedded tissue. Three of 10 (30%) ESTSCLE and five of five (100%) UTROSCT were inhibin and CD99 immunoreactive. Inhibin staining was confined to the areas with sex-cord-like differentiation, and staining was generally much stronger and more extensive in areas featuring prominent foam cells. There were no differences in the degree or intensity of staining for inhibin in premenopausal and postmenopausal women. CD99 expression tended to correlate with inhibin and was typically confined to similar cell types in the individual neoplasms. Weak CD99 immunoreactivity was seen in one additional epithelioid smooth muscle tumor, whereas all other mesenchymal and epithelial neoplasms studied for inhibin and CD99 were negative. These results provide further immunohistological support for true sex-cord differentiation within uterine mesenchymal proliferations and suggest that the degree of sex-cord differentiation may correlate with the expression of these markers.

Value of inhibin in the identification of granulosa cell tumors of the ovary.

Inhibins are peptide hormones that participate in the regulation of the pituitary-gonadal feedback system and are selectively expressed by cells of sex cord-stromal derivation. To determine the efficacy of this marker for distinguishing granulosa cell tumors, 134 primary and metastatic lesions of the ovary were evaluated for expression of the alpha-subunit of inhibin in routinely processed formalin-fixed, paraffin-embedded tissue. A variety of sex cord-stromal tumors (SCST), including 35 adult and juvenile granulosa cell tumors, 14 fibroma-thecomas, and 18 other sex cord-stromal proliferations, were studied. In addition, 33 surface epithelial neoplasms, 12 germ cell tumors, 11 metastases, and 11 miscellaneous ovarian neoplastic proliferations were evaluated. Among the non-granulosa cell neoplasms, special emphasis was placed on primary neoplasms and metastases that histologically simulated granulosa cell tumors. Thirty-three of 35 (94%) granulosa cell tumors were immunoreactive compared with 2 of 12 (17%) primary ovarian endometrioid tumors, one of nine (11%) primary ovarian transitional cell (Brenner) proliferations, and 3 of 17 (18%) other primary and metastatic poorly differentiated (undifferentiated) carcinomas. In 31 of the 35 granulosa cell tumors, inhibin staining was of moderate to strong intensity or was present in at least half of the constituent cells, whereas only 2 of 33 primary surface epithelial neoplasms fulfilled the same criteria, showing weak staining of 70% to 80% of the cells. In contrast, 10 of 14 (71%) ovarian fibroma-thecomas and 17 of 18 (94%) other sex cord-stromal proliferations were positive for inhibin. Nonneoplastic luteinized stromal cells stained for inhibin in 29 of 85 cases in which they could be evaluated. The results of this study show that although it is not completely specific and cannot reliably distinguish granulosa cell tumors from fibroma-thecomas or other ovarian sex cord-stromal proliferations, inhibin can be used to help distinguish sex cord-stromal neoplasms from most primary and metastatic non-SCST. Caution should be exercised in the interpretation of inhibin-positive cells, because a wide variety of primary and metastatic ovarian tumors may contain significant numbers of positively staining luteinized cells.

Expression of the estrogen receptor gene in developing and adult human breast.

Although studies of the estrogen receptor gene abound in rodent models and breast cancer cell lines, little is known about expression of this gene in normal human breast. Information regarding the physiology of this gene's expression is important if we are to elucidate abnormalities of the gene that may be involved in breast carcinogenesis. We evaluated levels of mRNA expression of the estrogen receptor (ER) gene and its protein product in a set of 89 breasts from clinically normal female infants, children, adolescents, and adult premenopausal and post-menopausal women. mRNA expression of the gene varied with the hormonal status. Relatively higher levels of gene transcripts were found in breasts of peri-menarchal girls, women in the luteal phase of the menstrual cycle, and in those with fibrocystic change. Higher levels were also occasionally found in breasts of infants and in most pre-adolescent children. Lower levels were seen in breasts of women in the follicular phase of the menstrual cycle, during pregnancy, and after menopause. Nuclear protein staining was common in breasts of normal children and peri-menarchal adolescents, and in post-menopausal atrophic breasts. Nuclear ER protein was infrequently detected in reproductive aged women's breasts, but was more often seen in follicular than in luteal menstrual phase or pregnant breast. ER protein was more frequently seen in post-menopausal than in pre-menopausal breasts with fibrocystic change. The results fit a model in which circulating levels of estrogen are inversely related to levels of mRNA transcribed from the estrogen receptor gene in normal physiologic states. Abnormally high levels of gene transcription may occur in some cases of fibrocystic change.

Fine needle aspiration of abdominal fat for the diagnosis of amyloidosis.

Amyloidosis is a dysproteinemia characterized by extracellular deposition of amyloid fibrils. Its diagnosis depends on the demonstration of the characteristic apple-green birefringence in tissue stained with Congo red. Aspiration of subcutaneous fat as a means of procuring tissue has received attention in the internal medicine literature. However, this application of fine needle aspiration biopsy has not been investigated extensively by cytopathologists. We therefore report our experience. Over the past two years we performed 18 aspirations of subcutaneous fat on 17 patients in whom amyloidosis was clinically suspected. Eight aspirates were positive for amyloid, and nine were negative. There were no known false-negative results. False positives were more problematic, occurred early in our experience and were due to overinterpretation of occasional long, slender, green strands representing collagen. The true positives were all characterized by large numbers of short, apple-green strands intimately associated with the fat, oriented in multiple directions and occurring in much, if not all, of the aspirated fat. Attention to details of the aspirated material other than the presence or absence of apple-green birefringence can lead to a correct distinction between amyloid and collagen. We conclude that abdominal fat pad aspiration is useful in the workup of suspected amyloidosis, especially since it is a safe, easily performed procedure.