[Neuroendocrine neoplasms of the breast]. / Neuroendokrine Neoplasien der Mamma.

Neuroendocrine neoplasms (NEN) of the breast are specific tumor entities. According to the literature up to 5% of breast neoplasms are malignant epithelial neoplasms of the breast. They are defined by a neuroendocrine (NE) architecture and cytology combined with an expression of the neuroendocrine vesicle markers chromogranin A and/or synaptophysin. The diagnosis is supplemented by the receptor status and the proliferative activity. According to the World Health Organization (WHO) classification of 2012 the following groups of NEN are distinguished: (1) invasive breast carcinoma with NE differentiation, (2) well-differentiated neuroendocrine tumor (NET) and (3) poorly differentiated small cell carcinoma (NEC). This review article focuses on (1) the definition and basic principles of diagnostics, (2) the history, nomenclature and WHO classification from 2003 and 2012, (3) the frequency of breast NEN, (4) the hereditary background and functional activity, (5) the expression of receptors and (6) the possible clinical implications. In addition, the first results of a retrospective single center study (n = 465 patients with breast cancer over a time period of 4 years) on the frequency of NEN of the breast at the Breast Center of the University Hospital Düsseldorf are presented. In this study a frequency of 4.5% of NEN was found based on a diagnostic cut-off of > 50% Chromogranin A and/or synaptophysin positive tumor cells.

Primary intratesticular sarcoma of the testis: a rare manifestation of testicular cancer.

A 57-year-old white male presented with a 5-month history of a painless right testicular mass. Physical examination revealed a right testicular tumor. The patient underwent a right inguinal orchiectomy. Histopathologic evaluation showed a primary spindle-cell sarcoma of the testis. A retroperitoneal lymph node dissection was performed and revealed no lymphatic metastases. There was no recurrence of the disease over a 2-year follow-up period.

Expression patterns of angiogenic and lymphangiogenic factors in ductal breast carcinoma in situ.

The objective of this study was to investigate expression of various growth factors associated with angiogenesis and lymphangiogenesis and of their receptors in ductal carcinomas in situ of the breast (DCIS). We studied protein expression of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF)-A, endothelin (ET)-1, and VEGF-C, and their receptors bFGF-R1, Flt-1, KDR, ET(A)R, ET(B)R, and Flt-4 immunohistochemically in 200 DCIS (pure DCIS: n=96; DCIS adjacent to an invasive component: n=104) using self-constructed tissue microarrays. Basic fibroblast growth factor-R1, VEGF-C, Flt-4, and ET(A)R were expressed in the tumour cells in the majority of cases, whereas bFGF and Flt-1 expression was rarely observed. VEGF-A, KDR, ET-1, and ET(B)R were variably expressed. The findings of VEGF-C and its receptor Flt-4 as lymphangiogenic factors being expressed in tumour cells of nearly all DCIS lesions and the observed expression of various angiogenic growth factors in most DCIS suggest that in situ carcinomas are capable of inducing angiogenesis and lymphangiogenesis. Moreover, we found a higher angiogenic activity in pure DCIS as compared to DCIS with concomitant invasive carcinoma. This association of angiogenic factors with pure DCIS was considerably more pronounced in the subgroup of non-high-grade DCIS (n=103) as compared with high-grade DCIS (n=94). Determination of these angiogenic markers may therefore facilitate discrimination between biologically different subgroups of DCIS and could help to identify a particularly angiogenic subset with a potentially higher probability of recurrence or of progression to invasiveness. For these DCIS, targeting angiogenesis may represent a feasible therapeutic approach for prevention of progression of DCIS to invasion.

[Multiple synchronous small intestine carcinomas. A rare case observation]. / Multiple synchrome Dünndarmkarzinome. Eine seltene Fallbeobachtung.

We report on the extremely rare finding of a multiple synchronous, partly free perforated carcinoma of the small bowel. The histopathological diagnosis was a small-cell carcinoma of the small bowel. Malignant lymphoma, neuroendocrine or neuroendothelial malignancies were excluded immunohistochemically. In light of the intraoperative finding and the postoperative diagnostics, we are of the opinion that it is a primary multiple synchronous carcinoma of the small bowel.

Estrogen induces expression of endometrial epidermal growth factor receptors before implantation.

PROBLEM: Pharmacological doses of 17 beta-estradiol increase epidermal growth factor binding to uterine membranes. METHODS: To determine whether physiological elevated E2 concentrations in the preimplantation phase of rabbits and preovulatory phase of women cause epidermal growth factor (EGF) receptor expression, we performed radioligand binding studies of endometrial membranes with [125I]-EGF. RESULTS: Unmated rabbits revealed a binding maximum (Bmax) of 514 +/- 197 fmol/mg protein for [125I]-EGF. The Bmax values increased significantly to 1424 +/- 430 fmol/mg on day 1 and to 2244 +/- 224 fmol/mg on day 2 after mating. On day 3 the Bmax values decreased to 1409 +/- 238 fmol/mg and on days 4 to 8 the binding maxima were not significantly different from the Bmax values of unmated rabbits. In ovariectomized rabbits a significant increase of [125I]-EGF-binding could be mimicked 12 and 18 h after the intramuscular injection of estradiol (40 micrograms/kg). The estradiol-induced increase of [125I]-EGF Bmax values was blocked by the parallel application of the antiestrogen tamoxifen. Progesterone (2 mg/kg) did not influence [125I]-EGF-binding to endometrial membranes. Membrane preparations of the human endometrium from the periovulatory phase bound significantly more [125I]-EGF compared to endometrium of the early proliferative phase. The expression of EGF receptor mRNA was localized in the epithelial cells of the human endometrium by in situ hybridization technique. CONCLUSIONS: These results provide insight into the regulation of the autocrine and paracrine factor EGF in the endometrium during the preimplantation period.

[Occurrence of CD44 and its isoforms under orthological and pathological conditions]. / Das Vorkommen von CD44 und seinen Isoformen unter orthologischen und pathologischen Bedingungen.

Variant isoforms of CD44 have been strongly implicated in malignant transformation and cancer metastasis. To ascertain the pattern of expression of these isoforms in human normal, fetal and tumor tissues (breast carcinomas, renal cell carcinomas, malignant melanomas, colon carcinomas, non-Hodgkin-lymphomas, neuroblastomas and brain tumors), we generated monoclonal antibodies against CD44 variant regions. Monoclonal antibodies were produced against variant regions encoded by exons 4v, 6v and 9v. CD44 variant isoforms are expressed on normal epithelial cells in a different pattern. Regions of epithelia that expressed the highest levels of the variant isoforms were those with a high rate of cell division. CD44 variant isoforms were not expressed by all investigated tumors (not by malignant melanomas, brain tumors and neuroblastomas). It is interesting that the expression of CD44 isoforms in non-Hodgkins lymphomas and colon carcinomas shows possibly a correlation with malignancy.

Cytokeratin expression and vimentin content in large cell anaplastic lymphomas and other non-Hodgkin's lymphomas.

The immunophenotypes of 74 malignant lymphomas (9 Hodgkin's disease, 19 low-grade B-cell, 20 high-grade B-cell, 8 T-cell, and 18 large cell anaplastic lymphomas [LCAL]) have been characterized with antibodies against leucocyte differentiation antigens, keratin, and vimentin. All the non-LCAL were CD45 positive and keratin negative. The LCALs had a more varied immunophenotype, with CD45 present only in 11 of 18 cases and keratin present in 5 of 18 of these rare lymphomas. The lymphoid origin of these latter cases was proven by gene rearrangement studies. All LCALs were CD30+, and, where tested, vimentin positive. Of four different vimentin monoclonal antibodies tested, V9 and MVI stained the highest number of lymphomas. Positive staining of tumor cells was seen in 61 of 71 cases. Vimentin-negative cases included Burkitt's as well as some follicular lymphomas.