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All assays performed in anatomic and clinical pathology laboratories must be validated before they are placed into clinical service. This review summarizes strategies for validation of clinical immunohistochemistry assays, and is chiefly based on the recently released guideline released by The College of American Pathologists.

The clinical, pathologic, and molecular features of pleomorphic lobular carcinoma in situ (PLCIS) and the relationship of PLCIS to classic LCIS (CLCIS) are poorly defined. In this study, we analyzed 31 cases of PLCIS (13 apocrine and 18 nonapocrine subtypes) and compared the clinical, pathologic, immunophenotypic, and genetic characteristics of these cases with those of 24 cases of CLCIS. Biomarker expression was examined using immunostaining for E-cadherin, gross cystic disease fluid protein-15, estrogen, progesterone, androgen receptor, human epidermal growth factor receptor2, CK5/6, and Ki67. Array-based comparative genomic hybridization to assess the genomic alterations was performed using microdissected formalin-fixed paraffin-embedded samples. Patients with PLCIS presented with mammographic abnormalities. Histologically, the tumor cells were dyshesive and showed pleomorphic nuclei, and there was often associated necrosis and microcalcifications. All lesions were E-cadherin negative. Compared with CLCIS, PLCIS showed significantly higher Ki67 index, lower estrogen receptor and progesterone receptor expression, and higher incidence of HER2 gene amplification. The majority of PLCIS and CLCIS demonstrated loss of 16q and gain of 1q. Apocrine PLCIS had significantly more genomic alterations than CLCIS and nonapocrine PLCIS. Although lack of E-cadherin expression and the 16q loss and 1q gain-array-based comparative genomic hybridization pattern support a relationship to CLCIS, PLCIS has clinical, mammographic, histologic, immunophenotypic, and genetic features that distinguish it from CLCIS. The histologic features, biomarker profile, and genomic instability observed in PLCIS suggest a more aggressive phenotype than CLCIS. However, clinical follow-up studies will be required to define the natural history and most appropriate management of these lesions.

Sentinel lymph node biopsy has been shown to be an accurate predictor of axillary nodal status in invasive breast cancer and is a useful alternative to axillary dissection for some patients. Because radioactive materials are often used to identify the sentinel lymph node, concerns have been raised regarding the safe handling of tissue specimens obtained by this technique. The Surgical Pathology Committee of the College of American Pathologists and the Association of Directors of Anatomic and Surgical Pathology have developed recommendations for the safe handling of radioactive specimens obtained by sentinel lymphadenectomy.

Analysis of the DNA content of various solid tumors and hematological malignancies may provide useful prognostic information. To date, however, there has been a striking lack of correlation between DNA content in neoplasms of the central nervous system and clinical behavior. Simultaneous quantitation of DNA content and proliferation-associated nuclear antigen (p105) by flow cytometry was performed on paraffin-embedded tissues representing three major groups of central nervous system neoplasms—1) 21 astrocytic tumors, 2) 13 pituitary tumors, and 3) 19 meningiomas-and the results were correlated with clinical behavior. All 4 well-differentiated gliomas were diploid, while 3 of 9 anaplastic astrocytomas and 1 of 8 glioblastomas had a demonstrable aneuploid peak. Three of 13 pituitary tumors had an identifiable aneuploid peak, while only 2 of 19 meningiomas had an aneuploid DNA content. Cell-cycle analysis of the malignant gliomas revealed a significantly higher proliferative index (PI, %S + G2M) compared with the well-differentiated astrocytomas (P< 0.05). Within the subgroup of diploid anaplastic astrocytomas, however, extended patient survival appeared to be associated with a higher PI. For diploid pituitary adenomas, the PI was consistently lower in the 3 tumors that recurred than it was in the remaining 8 adenomas. Nuclear antigen quantitation of diploid tumors showed a wide range of p105 expression in G0G1cells, suggesting that, within each tumor, the cells are heterogeneous with respect to proliferative activity. Aneuploid nuclei of glial tumors showed enhanced expression of p105 relative to diploid cells of the same specimen. In pituitary tumors, the median G2M/G0G1fluorescence ratio for p105 was significantly higher (P< 0.05) for the 3 diploid recurrent tumors than for those that did not recur. These data support the assumption that the aggressive clinical course of malignant glial neoplasms may be related to an abnormal DNA stemline and/or an alteration in cell proliferative activity. Cell cycle analysis and measurement of p105 by this technique may provide information useful from both a prognostic standpoint and in directing adjuvant therapy.

Simultaneous flow cytometric quantitation of DNA content and the proliferation-associated nuclear antigen pl05 was performed on 41 gastrointestinal smooth muscle neoplasms and the results were correlated with histologic features. Aneuploid DNA stemlines were found in 17 cases (41%), including four o

We report the histologic and ultrastructural findings on two sisters with familial visceral myopathy who presented with acquired megacolon that necessitated subtotal colectomy. Both patients were mentally retarded and had repeated episodes of constipation and fecal impaction. Each presented near the age of 30 with massive dilatation of the colon and without clinical evidence of small intestinal involvement. Histologic abnormalities primarily involved smooth muscle and included marked nuclear enlargement and irregularity, interstitial fibrosis, and cytoplasmic vacuolation. These changes were most severe in the muscularis propria, but similar abnormalities were found in the muscularis mucosae and blood vessels. In the most advanced stages, collagen had completely replaced the muscularis propria, with extreme thinning of the intestinal wall. Abnormalities were noted in all segments of the colon and the appendix, but there was little correlation between severity of involvement and the segment examined. This study not only confirms the variable nature of morphologic changes in familial visceral myopathy, but also provides evidence of more extensive involvement of intestinal smooth muscle than has been previously reported.