Aleksander Talerman

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.

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 irnmunohistochemically 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.

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.

Cytogenetic study of botryoid rhabdomyosarcoma of the uterine cervix

We report a case of sarcoma botryoides of the uterine cervix occurring in a 19-year-old woman. By light microscopy the tumor showed round and spindle cells with hyperchromatic nuclei and, focally, a cambium layer subjacent to the surface epithelium and surrounding endocervical glands. Strap-shaped cells with and without cross-striations and small foci of immature cartilage were also present. Immunohistochemical studies showed positive staining within the tumor cells for myoglobin, desmin, vimentin, muscle-specific actin and CD56. By electron microscopy, tumor cells showed cytoplasmic filaments in an alternating pattern of thick and thin filaments. Chromosomal analysis demonstrated deletion of the short arm of chromosome 1, and trisomies 13 and 18. To our knowledge, this is the first reported case of sarcoma botryoides of the endocervix with chromosomal analysis.

Polymorphous Low-Grade Adenocarcinoma of the Vulva and Vagina: A Tumor Resembling Adenoid Cystic Carcinoma

We report the first case of a polymorphous low-grade adenocarcinoma (PLGA) occurring in the vulva and vagina of a 32-year-old woman. This tumor consisted of cellular lobules with distinct cribriform, papillary, and cystic patterns. Owing to its location and its distinct cribriform pattern, this lesion was initially diagnosed as an unusual variant of adenoid cystic carcinoma (ACC). However, this diagnosis was revised to PLGA when it was recognized that the cribriform, papillary and cystic patterns and their concomitant occurrence in the same lesion are characteristic of PLGA. PLGA should be added to the differential diagnosis of vulvar and vaginal neoplasia.

Morphologic, immunohistochemical, and fluorescence in situ hybridization study of ovarian embryonal carcinoma with comparison to solid variant of yolk sac tumor and immature teratoma

The prognosis and therapy for malignant ovarian germ cell tumors including embryonal carcinoma differ from those of other categories of ovarian tumors, making accurate diagnosis imperative for patient care. Because of its rarity, the protein markers and genomic alterations typifying primary ovarian embryonal carcinoma have not been fully characterized. The present study aims to establish a set of sensitive and specific protein markers useful for the diagnosis and delineation of ovarian embryonal carcinoma. Chromosomal 12p anomalies were analyzed by dual-color fluorescence in situ hybridization. In a series of 6 ovarian mixed germ cell tumors with a component of embryonal carcinomas, OCT4, CD30, SOX2, and glypican 3 expressions were analyzed immunohistochemically on formalin-fixed paraffin-embedded tissue specimens. The results were compared to 4 cases of mixed germ cell tumor that were originally mistaken for embryonal carcinoma. OCT4 marked the nuclei of 6 cases, among which 5 cases also showed glypican 3 expression indicative of an admixed yolk sac tumor component. SOX2 was positive in only 3 cases of embryonal carcinoma. In 1 case of mixed germ cell tumor containing embryonal carcinoma, embryoid bodies from a component of polyembryoma were demonstrated to be both OCT4 and CD30 positive. Two cases originally classified as embryonal carcinoma were OCT4 and CD30 negative and showed glypican 3 positivity. They were reclassified as solid variant of yolk sac tumor. Two other cases originally classified as embryonal carcinoma were OCT4 positive and CD30 negative and were classified as immature teratoma with neuroectodermal differentiation based on the immunohistochemical findings as well as morphologic features and were diagnosed as immature teratoma. Chromosome 12p alterations were identified in 5 of 6 cases of embryonal carcinomas. In summary, a panel of immunostains is more useful than a single biomarker in the differential diagnosis of ovarian germ cell tumors. Chromosome 12p fluorescence in situ hybridization combined with OCT4, CD30, and glypican 3 immunostains is useful in confirming the diagnosis of ovarian embryonal carcinoma.

Ki-A10, a germ cell nuclear antigen retained in a subset of germ cell-derived tumors.

Monoclonal antibody Ki-A10 recognizes a nuclear antigen of 25 and 22 kd apparent molecular mass, which is abundantly expressed by immature gonocytes, spermatogonia, and spermatocytes, whereas it is absent in spermatids, spermatozoa, oocytes, and normal somatic tissues. In a broad spectrum of human cancers the antibody showed no reactivity except for a small subset of malignant lymphomas. Because of this restricted expression pattern, we examined 173 germ cell tumors and 18 sex cord stromal tumors immunohistochemically to assess the distribution of the Ki-A10 antigen. A strongly positive reaction was found in classic seminomas, dysgerminomas, spermatocytic seminomas, and the germ cell component of gonadoblastomas. Yolk sac tumors presented a heterogeneous reactivity pattern ranging from overall positivity to complete lack of antigen expression, and in three of eight choriocarcinomas, a few clusters of cytotrophoblast cells were strongly labeled. All other tumors, including Leydig and Sertoli cell tumors as well as placental tissue, were negative. Our findings suggest that specific germ cell antigens can be retained in germ cell tumors along particular differentiation pathways. Ki-A10 is the first marker that consistently labels spermatocytic seminoma, further confirming its germ cell origin and suggesting a close relationship to classic seminoma. The antibody may serve for diagnostic purposes and promises new insights into the process of germ cell differentiation and the development of germ cell-derived neoplasia.

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 underrepresentation 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.

History of gynecological pathology XXV. Dr Gunnar Teilum.

This article represents the Silver Anniversary Essay in the Journal History Series, and it is fitting that the subject is a luminous figure in the history of gynecologic pathology, Dr Gunnar Teilum (Fig. 1). The original contributions of this distinguished investigator, largely but by no means solely devoted to gynecologic and to a lesser extent testicular pathology, and his book, represent a great legacy (1–19). We expand here on an appreciation written by one of us soon after Dr Teilum’s death (20). Another tribute was paid during his life to celebrate his 70th birthday (21). A special supplement to Acta Pathologica et Microbiologica Scandinavica began with an appreciation by Dr Harald Gormsen that included a listing of all Dr Teilum’s papers (22). It was followed by a series of invited reviews written by international authorities who focused on Dr Teilum’s areas of interest. In addition, recent essays on the history of gonadal-gynecologic pathology have included discussion of Dr Teilum as he was clearly one of the foremost individuals to merit coverage in them (23,24). He was one of the 6 individuals whose photograph adorned the cover of the journal containing one of those contributions (23). Despite these previous considerations, and the knowledge many readers will have of Dr Teilum’s work, we felt it time he was covered in this series. In the ensuing pages, we consider his life and work based on sources already noted, his papers, and input on his personal life by the middle author, his daughter-in-law. Gunnar Teilum was born on August 18, 1902 in Elsinore, a town on the northeast coast of the island of Zealand in Eastern Denmark. The town is famous for its link to the castle in Shakespeare’s Hamlet (Kronborg Castle from 1577). His parents were Laurits Oluf Pedersen and Karen Boline Marie Pedersen. The reader will immediately be struck by the surname of the parents being Pedersen, not Teilum. Pedersen is a common name in Denmark, and in their late teenage years Gunnar and his only sibling, his brother Svend, decided to change their surname to something less common and chose ‘‘Teilum.’’ It was apparently constructed out of ‘‘thin air’’ as it has no meaning in Danish, and to the best of the knowledge of one of us (D.T.), the only persons having this surname are the heirs of Dr Teilum and those who by marriage took the name. Gunnar’s father was the curator of the town museum and this, at least in part, likely led to Gunnar’s lifelong appreciation of art, and the interesting history of his town probably provoked a similar interest in history. His appreciation of art was shown not only by his being very knowledgeable about Danish painting, examples of which he collected, but also by his lectures, in which he sometimes made comparisons between paintings and light microscopy. After graduation from high school in 1921, Gunnar entered the medical school of the University of Copenhagen from which he From the Section of Breast Surgery (D.T.), Rigshospitalet, Copenhagen; and James Homer Wright Pathology Laboratories (R.H.Y.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. It is with sadness that we record that Dr A. Talerman died while this essay was in preparation. The authors declare no conflict of interest. Address correspondence to Robert H. Young, MD, James Homer Wright Pathology Laboratories, Massachusetts General Hospital, Boston, MA 02114. E-mail: rhyoung@partners.org.

Lectin Histochemistry of Sex Cord-Stromal Tumors and Small Cell Carcinoma of the Ovaries

Binding sites of peanut agglutinin (PNA), Ulex europaeus (UEA-1), concanavalin A (Con A), and wheat germ agglutinin (WGA) were localized in 10 granulosa cell tumors, 10 Sertoli-Leydig cell tumors, 4 theca cell tumors, and 5 small cell carcinomas. Con A and WGA reacted positively with the majority of the studied neoplasms. PNA and UEA-1 were persistently negative in the sex cord-stromal tumors (SCST) but showed focal positivity in small cell carcinomas. Negative reactions of SCST with PNA and UEA-1 may serve for differentiation between them and common epithelial tumors that are usually PNA and UEA-1 positive.