Testing for her2 in breast cancer: current pathology challenges faced in Canada.

This review is designed to highlight several key challenges in the diagnosis of human epidermal growth factor receptor 2 (her2)-positive breast cancer currently faced by pathologists in Canada: Pre-analysis issues affecting the accuracy of her2 testing in non-excision sample types: core-needle biopsies, effusion samples, fine-needle aspirates, and bone metastasesher2 testing of core-needle biopsies compared with surgical specimensCriteria for retesting her2 status upon disease recurrenceLiterature searches for each topic were carried out using the medline, Embase, International Pharmaceutical Abstracts, and biosis databases. In addition, the congress databases of the American Society of Clinical Oncology (2005-2011) and the San Antonio Breast Cancer Symposium (2007-2011) were searched for relevant abstracts.All authors are expert breast pathologists with extensive experience of her2 testing, and several participated in the development of Canadian her2 testing guidelines. For each topic, the authors present an evaluation of the current data available for the guidance of pathology practice, with recommendations for the optimization or improvement of her2 testing practice.

Ki 67 is a major, but not the sole determinant of Oncotype Dx recurrence score.

BACKGROUND: Immunohistological assessment of Ki 67 expression is less expensive than Oncotype Dx, which is currently used to identify patients with lymph node-negative breast cancer, who will benefit from adjuvant chemotherapy. METHODS: The relationship of immunohistologically measured Ki 67 to Oncotype DX recurrence score (RS) was examined in 53 cases of T1-2 N0 M0 (oestrogen receptor-positive, HER2/neu negative) breast cancer. RESULTS: There was a strong linear correlation between Ki 67 value and the Oncotype Dx RS. All patients in the low Ki 67 group (Ki 67 of ≤ 10%) had Oncotype Dx RSs of low or intermediate risk. The vast majority of patients (93.8%) in the high-Ki 67 group (Ki 67 ≥ 25%) had oncotype RSs of high or intermediate risk. CONCLUSION: Ki 67 proliferation value is a major, but not the sole determinant of Oncotype Dx score.

Infrared spectra of basal cell carcinomas are distinct from non-tumor-bearing skin components.

Infrared spectroscopy, by probing the molecular vibration of chemical bonds, directly indicates tissue biochemistry. An expanding body of literature suggests that infrared spectra distinguish diseased from normal tissue. The authors used infrared spectroscopy to examine basal cell carcinoma to explore distinctive characteristics of basal cell carcinoma versus normal skin samples and other skin neoplasms. Spectra of epidermis, tumor, follicle sheath, and dermis were acquired from unstained frozen sections, and analyzed qualitatively, by t-tests and by linear discriminant analyses. Dermal spectra were significantly different from the other skin components mainly due to absorptions from collagen in dermis. Spectra of normal epidermis and basal cell carcinoma were significantly different by virtue of subtle differences in protein structure and nucleic acid content. Linear discriminant analysis characterized spectra as arising from basal cell carcinoma, epidermis, or follicle sheath with 98.7% accuracy. Use of linear discriminant analysis accurately classified spectra as arising from epidermis overlying basal cell carcinoma versus epidermis overlying nontumor-bearing skin in 98.0% of cases. Spectra of basal cell carcinoma, squamous cell carcinoma, nevi, and malignant melanoma were qualitatively similar. Distinction of basal cell carcinoma, squamous cell carcinoma, and melanocytic lesions by linear discriminant analyses, however, was 93.5% accurate. Therefore, spectral separation of abnormal versus normal tissue was achieved with high sensitivity and specificity, which points to infrared spectroscopy as a potentially useful screening tool for cutaneous neoplasia.

Pituitary morphology in anencephalic human fetuses.

Anencephalic fetuses provide a model of pituitary development in the absence of the hypothalamus. We studied pituitaries of 10 anencephalic fetuses at various stages of gestation using formalin-fixed paraffin-embedded tissue with immunocytochemistry for known adenohypophysial hormones, the transcription factors Pit-1 and SF-1, cytokeratins and S-100 protein. Ten age- and sex-matched fetuses with no endocrine abnormality were controls. At 17-18 weeks of gestation, pituitaries of 4 anencephalics had no posterior lobe; the number and size of cells containing adenohypophysial hormones and the transcription factors were indistinguishable from controls, however, juxtanuclear cytokeratin-positive fibrous bodies were inconspicuous in anencephalics and were prominent in the adenohypophyses of controls. At 26-28 weeks of gestation, there was a marked reduction in number and staining intensity of cells containing SF-1, alpha-subunit of glycoprotein hormones and both gonadotropin beta-subunits in the adenohypophyses of 2 anencephalics. After 32 weeks, corticotropes were reduced in number and size, and gonadotropes were almost entirely absent; in contrast, somatotropes, lactotropes and thyrotropes were numerous. S-100 protein immunoreactivity was increased in anencephalic pituitaries after 32 weeks, when it was found in numerous cells that did not have the usual morphology of folliculo-stellate cells. These data indicate that adenohypophysial cells can differentiate in the absence of the hypothalamus, and that the transcription factors implicated in cytodifferentiation are expressed in anencephalic pituitaries, but that hypothalamic factors are essential for maintenance of gonadotropes and corticotropes. The functional role of fibrous bodies in somatotropes is unknown, but these structures are inconspicuous in the adenohypophyses of anencephalics. Finally, the appearance of S-100 protein-immunoreactive cells is abnormal in anencephalic fetuses.

Adenohypophyseal tissue in an immature teratoma of the human ovary.

An immature ovarian teratoma containing adenohypophyseal tissue with a central arteriole and interpositioned in mature neural tissue is reported in an asymptomatic 31 -year-old woman. The tumor was a grade 2 immature teratoma according to the modified ThurlbeckScully histological grading system. Immunocytochemistry showed positive staining for growth hormone, prolactin, adrenocorticotropin, and alpha-subunit human chorionic gonodotropin and negative staining for thyroid-stimulating, follicle-stimulating, and luteinizing hormones in the adenohypophysis. The absence of staining for growth-hormonereleasing and corticotropin-releasing hormones, somatostatin, vasopressin, and neurophysin in adjacent tissue is consistent with the view that adenohypophyseal development is independent of the influence of these peptides.

Immunoelectron microscopic identification of human parvovirus B19.

A mildly macerated, hydropic fetus was delivered spontaneously at 25 weeks gestation by a multigravidous black mother. At autopsy, gross and microscopic evidence suggested fetal anemia, and excessive extramedullary erythroblastosis was present generally. Erythroid precursor cells in the pulmonary capillary circulation contained eosinophilic nuclear inclusions consistent with human parvovirus B19 infection. Transmission electron microscopy on osmicated Epon lung sections showed lucent, granular chromatin corresponding to the inclusions. In rare foci only these sections contained paracrystalline arrays of 20-nm virions. In the same cells, similar virions were seen within the cytoplasm, both randomly distributed and in paracrystalline aggregates. Postembedding immunoelectron microscopy, done on formalin-fixed lung embedded in a hydrophilic resin, showed positive labelling over the nuclear inclusions, and also localized the viral capsid antigen to cytoplasmic virion aggregates. The nuclear aggregates suggest that the virus would reach the circulation after cell lysis whereas those in cytoplasm suggest that parvovirus also may be excreted from infected cells before they lyse.