Corrado D'Arrigo

Paget disease of the nipple - A multifocal manifestation of higher-risk disease

The treatment of Paget disease by mastectomy has been challenged recently in favor of breast‐conserving techniques. A large series of patients treated with mastectomy has been reviewed to assess the feasibility of less radical surgery.

Benign central neurocytoma

“Central neurocytoma” is classically considered as an intraventricular benign tumor, largely based on data from small retrospective series. The authors present prospective data on 12 patients with tumors diagnosed as central neurocytoma, to highlight the diverse nature of this tumor and challenge the classic notion.

Combination of microdissection and microarray analysis to identify gene expression changes between differentially located tumour cells in breast cancer

Comparison of gene expression changes between cancer cells at the periphery and in the centre of breast cancers was performed using a combination of microdissection and microarray analysis. Cancer cells from the two areas were pooled separately from five patients with ductal carcinoma in situ and separately from five patients with frankly invasive cancer. Limited total RNA, 100–200 ng, from this microdissected tissue required use of the Atlas SMART™ Probe Amplification Kit to synthesize and amplify cDNA and make 33P-labelled probes. Probes were then hybridized to Atlas Human Cancer 1.2 Arrays containing 1176 known genes. Triplicate analysis revealed that 22 genes changed their expression levels in the periphery relative to the central region: 15 upregulated and seven downregulated (arbitrary threshold of 1.5-fold or greater). Differences in RNA levels were confirmed by quantitative real-time PCR for two of the genes and by changes in protein levels, detected by immunohistochemistry, for a couple of representative gene products. Thus, changes in gene expression associated with variation in microanatomical location of neoplastic cells can be detected within even small developing tumour masses.

A Viral Aetiology for Breast Cancer: Time to Re-Examine the Postulate

Despite decades of research, no aetiologic factor(s) for human breast cancer has been identified and the search for a causal agent has all but been abandoned during the past thirty years. Over 60 years ago, it was demonstrated that breast tumours in mice are caused by an oncornavirus, murine mammary tumour virus (MMTV). Whilst many at that time postulated a similar virus might be the causative agent of human breast cancer, genetic evidence was difficult to obtain primarily because of the occurrence of endogenous human retrovirus (HER) sequences within the human genome that share extensive regions of nucleotide homology with MMTV. Recently, there has been a resurgence of interest in the possibility that a significant proportion of human breast cancers may be caused by viral infections. Two candidate viruses have been proposed, a human retroviral analogue of MMTV (which differs significantly in sequence and characteristics from HERs) and, the Epstein-Barr virus (γ-herpes virus). These two viruses have been reported to occur in up to 37 and 50% of breast cancer cases, respectively. Here we present the background to the infectious hypothesis for the aetiology of breast cancer and review recent findings.

Paget's disease of the nipple: A multi-focal manifestation of higher risk disease

BACKGROUND The treatment of Paget disease by mastectomy has been challenged recently in favor of breast-conserving techniques. A large series of patients treated with mastectomy has been reviewed to assess the feasibility of less radical surgery. METHODS The cases of 70 women with a clinical diagnosis of Paget disease were reviewed. The type, grade, receptor and node status, and the mammographic and pathologic extent of the underlying breast malignancy were determined. The survival of patients with invasive disease was compared with matched controls without Paget disease. RESULTS The underlying malignancy was invasive in 58% of cases. Despite the fact that only one third of women presented with a palpable mass, the malignancy was frequently extensive, being confined to the retroareolar region in only 25% of cases. The true extent of the disease was underestimated by mammography in 43% of cases. Of the patients with ductal in situ carcinoma, 96.5% had high-grade carcinomas and 100% had invasive carcinomas of high cytonuclear grade. Overexpression of the c-erb-B2 oncogene was detectable in 83% of cases. Patients with Paget disease had a significantly worse survival than matched controls, but this difference was eliminated if they were also matched for c-erb-B2 status. CONCLUSIONS Paget disease is often associated with extensive underlying malignancy, which is difficult to assess accurately either clinically or mammographically. As a consequence, cone excision of the nipple would have resulted in incomplete excision in 75% of cases. The underlying disease is of high grade and is frequently c-erb-B2 positive with a resulting poor prognosis. Aggressive local and systemic treatment would seem to be merited.

Pathology of breast carcinoma.

The pathologist examines biopsy material obtained at surgery or preoperatively by core biopsy to make a definitive diagnosis of malignancy and to determine the type and grade of the tumour. Additional prognostic information is provided to the clinician, and this includes the true tumour size and the relative contribution of the in situ and invasive components. Other important factors include multifocality, vascular invasion and the presence and extent of axillary nodal metastases. For optimal use of this important information, close cooperation between the members of the multidisciplinary team is essential.

Pathogenesis of breast carcinoma.

Breast cancer usually develops after a series of epithelial changes in the terminal ductolobular unit. There are multiple benign causes of breast lumps, the majority of which are not associated with an increased risk of breast cancer. Histological changes of pre‐malignancy such as atypical hyperplasia and in situ carcinoma can be identified, and these are indications for either close surveillance or further surgery. At the time of diagnosis, breast cancers can be staged both clinically and pathologically, and this facilitates international comparisons of results of treatment.

An alternative method of dissecting mastectomy specimens.

Sir: Although mastectomies are performed less frequently nowadays, as most mammary carcinomas are treated more conservatively, their careful dissection remains important. The main aim is usually evaluation of the extent of malignant disease or the presence of residual disease following previous therapy. Most standard protocols recommend slicing the breast from the posterior aspect, in a sagittal plane (at right angles to the skin) from medial to lateral or vice versa, leaving the skin intact to aid reconstruction and orientation. This, especially in large specimens, has the disadvantage of compressing the adipose tissue, which protrudes from the cut surface resulting in uneven slicing and loss of anatomical relationships. It is now accepted that, certainly in ductal carcinoma in situ (DCIS), neoplastic epithelium spreads from the periphery towards the nipple. Excision biopsy specimens, where DCIS is suspected, should therefore be serially sliced perpendicular to the ducts going in the direction of the nipple. Slicing such specimens parallel to the skin surface, thus cutting more along the line of the ducts, has also been suggested. This allows direct evaluation of tumour extension towards the nipple and is particularly suitable for large sections. We have explored the value of slicing mastectomy specimens parallel to the skin surface (Figure 1) to see if this facilitates evaluation of disease and produces more uniform slices. Attached axillary contents, if present, and any significant amount of muscle on the deep surface are removed and dissected separately. The deep ⁄ dorsal specimen surface and the 12 o’clock position are inked, the latter by a line from the edge of the skin ellipse to the deep margin (Figure 2a). The nipple and immediate subareolar tissue are removed and ink introduced