Expert opinion: Reporting needle core biopsies of breast carcinomas.

Many breast carcinomas are now diagnosed in needle core biopsies, after either mammographic detection or symptomatic presentation. There is dispute, however, about the range of information that should be included in the diagnostic report of these small and possibly unrepresentative samples. Is it sufficient to simply report the presence of carcinoma, in situ or invasive? Or should the histopathologist give a more detailed report including features of prognostic and predictive significance? If so, what is the evidence that the further information is, first, of clinical benefit and, second, not unreliable because of sampling variability? To address the question "What should be included in reports of needle core biopsies of breast carcinomas?" contributions were invited from authors in the USA and the UK.

Intraepidermal cytokeratin 7 immunoreactive cells in the non-neoplastic nipple may represent interepithelial extension of lactiferous duct cells.

AIMS: The interpretation of cytokeratin 7 (CK7)-positive cells in the epidermis of the nipple has been controversial. These cells have been described in Paget's disease of the nipple, and they have also been cited as benign 'Toker' cells or as Merkel cells. Having observed CK7+ cells in histologically unremarkable nipple biopsies, we sought to assess the distribution of CK7+ cells in Paget's disease of the nipple and in histologically unremarkable nipple. METHODS AND RESULTS: Representative sections from 37 cases of Paget's disease of the nipple and 32 cases of histologically unremarkable nipple were obtained. The histologically unremarkable nipple sections were taken from prophylactic mastectomies (n=17) and from autopsies of patients who did not have breast cancer (n=15). CK7 immunostaining was performed on sections from formalin-fixed paraffin blocks. Sequential sections were immunostained with antibodies to low-molecular weight cytokeratin-CAM 5.2 and HER-2/neu. CK7+ cells were present in the epidermis around the opening of the lactiferous ducts in Paget's disease (95%) and in histologically unremarkable nipple (45%) cases. CK7+ cells diminished in number with increasing distance from the orifice of the lactiferous ducts. The lactiferous duct epithelium in Paget's disease and in histologically unremarkable nipple was CK7+ in all specimens when this element was present. CAM5.2 immunostaining had a similar but weaker pattern of reactivity. HER-2/neu reactivity was seen in 68% cases of Paget's disease and was negative in all cases of histologically unremarkable nipple. Tumour cells in two cases of Paget's disease were CK7-. In one of these, the underlying breast carcinoma was also CK7-, the only CK7- tumour in this series. In the other case, the normal lactiferous duct was CK7+ and no underlying carcinomatous tissue was available to study. CONCLUSIONS: The presence of CK7+ cells does not equate to Paget's disease of the nipple. Intraepidermal CK7+ cells in the non-neoplastic nipple can be a manifestation of interepithelial extension of benign lactiferous duct cells. The increased presence of CK7+ cells in Paget's disease probably results either from neoplastic transformation of native intraepithelial lactiferous duct cells or form direct extension/migration of neoplastic cells into the nipple. The distribution of CK7 immunoreactive cells in the nipple epidermis can be helpful in the diagnosis of Paget's disease of the nipple.

Cytokeratin 19 immunoreactivity in the diagnosis of papillary thyroid carcinoma: a note of caution.

To evaluate the expression of cytokeratin (CK) 19, we stained sections obtained from formalin-fixed, paraffin tissue blocks of 35 thyroid tumors (follicular adenoma [FA], 20; papillary thyroid carcinoma [PTC], 10 follicular variant [FV] and 5 usual type) and scored the extent of staining as follows: 1+ (<5% positively stained cells), 2+ (5%-25% positively stained cells), 3+ (25%-75% positively stained cells), and 4+ (>75% positively stained cells). All 15 PTCs (including 10 FV-PTCs) were CK19 positive: 14 were 4+ and 1 (FV-PTC) was 2+. All 20 FAs also were CK19 positive: 15 were 1+, 1 was 2+, 4 were 3+, and none was 4+. In the FAs that were scored 1+, reactivity usually was confined to follicular cells lining cystically dilated atrophic follicles that lacked the typical nuclear features of PTC. The remaining FAs showed more diffuse reactivity, which was, however, less intense than that observed in the PTCs. Thus, immunoreactivity for CK19 is not specific for PTC, although we acknowledge that the extent and intensity of staining are considerably greater in this tumor than in FA. There were no significant differences in staining for CK19 between nonneoplastic follicles adjacent to PTCs and those adjacent to FAs.

A potential source of false-positive sentinel nodes: immunostain misadventure.

The clinical and pathologic aspects of sentinel lymph node biopsy have generated much attention. Pitfalls in the pathologic handling of sentinel lymph node specimens have received little attention. We report a case in which a false-positive diagnosis might have been rendered on a sentinel lymph node because of an inadvertent immunostaining error. Attention was drawn to the problem by an unusual pattern of distribution of immunoreactive cells-which proved to be plasma cells rather than metastatic carcinoma cells.

Synchronous water-clear cell double parathyroid adenomas a hitherto uncharacterized entity?

Water-clear cell hyperplasia is a rare but well-documented cause of primary hyperparathyroidism. Parathyroid adenomas of the water-clear cell type are exceptionally rare, and only 2 cases have been reported. We describe a patient with synchronous water-clear cell double parathyroid adenomas, an entity that has not previously been reported. In our case, the enlarged superior parathyroid glands were completely replaced by water-clear cells, with only a minute rim of extracapsular, histologically unremarkable parathyroid tissue. The inferior parathyroid glands were grossly unremarkable, and incisional biopsy specimens were histologically normal (no foci of water-clear cells were identified). The findings in this case are most consistent with the diagnosis of double adenomas of the water-clear cell type. We acknowledge that despite molecular proof of monoclonality of the 2 lesions, it is not possible to entirely exclude the possibility that this unusual case could be due to asymmetric hyperplasia.

Are microinvasion and micrometastasis in breast cancer mountains or molehills?

BACKGROUND: The increased rate of early detection of breast cancer due to widespread mammographic screening has led to an increased incidence of in situ as well as microinvasive carcinoma. The enhanced pathological examination to which sentinel lymph nodes are subjected has led to an increased rate of detection of micrometastatic carcinoma. Despite the augmented rate of diagnoses of both diseases, the pathological diagnoses as well as clinical management of these entities continue to be controversial. DATA SOURCES: A computerized literature search was performed on the Medline and PubMed database from 1990 to date. Relevant earlier publications were also perused. The database of the Department of Pathology at New York Presbyterian Hospital-Well Medical College of Cornell University were also accessed. CONCLUSIONS: Based on cumulative data, patients diagnosed with either microinvasive or micrometastatic carcinoma of breast have a relatively favorable, albeit guarded, prognosis. Treatment recommendations for both of these disease entities continue to be controversial, and may remain so until additional refined clinicopathological data becomes available.

Microinvasive carcinoma (T1mic) of the breast: clinicopathologic profile of 21 cases.

Clinicopathologic data on microinvasive carcinoma of the breast (MICB) as defined by the 1997 TNM criteria (T1mic < or = 1 mm) is scarce. Histologic slides of 109 cases from 1993 through 1997, in which microinvasion was either suspected or diagnosed initially, were reviewed. A double immunoenzyme-labeling technique using antismooth muscle actin and anticytokeratin antibody on the same section was used to confirm invasion in equivocal cases. All foci of invasion were measured by ocular micrometer. Twenty-one cases were confirmed to be MICB. The mean age of the patients was 60.9 years. Thirteen patients presented with mammographic abnormalities on routine examination (60.9%). MICB was ductal in 18 patients, including one tubular carcinoma, and was lobular in three patients. The mean number of invasive foci was two per patient (range, one to seven foci). The accompanying duct carcinoma in situ had high-grade nuclei and necrosis in 16 of 18 patients (89%), 13 of which (72%) were comedo-type. Two of the 15 patients had one positive axillary lymph node each (13.3%). Eleven patients underwent mastectomy, nine received radiation therapy, one received chemotherapy, and two underwent lumpectomy only. Median follow up was 28 months (range. 18-63 months). One patient had a chest wall recurrence of infiltrating duct carcinoma and another recurred with duct carcinoma in situ.

Determination of size in invasive breast carcinoma: pathologic considerations and clinical implications.

The widespread use of mammography has made the detection of increasingly small, often impalpable, invasive breast carcinomas possible. An enhanced understanding of morphological factors, among the foremost of which is size of invasive component of carcinoma, is changing the management of breast cancer To the uninitiated, the determination of size of invasive component is seemingly simple but in practical terms is complicated by a number of ambiguous issues. Practical guidelines for the assessment of size of invasive carcinoma are proposed.

Quantifying mammary duct carcinoma in situ: a wild-goose chase?

Duct carcinoma in situ (DCIS) is a malignant neoplasm of the breast that is limited to the glandular component. The introduction of mammographic screening allows for earlier detection of carcinoma, at the stage of DCIS, before it invades the surrounding stroma. Although DCIS has been studied extensively, its quantification remains a dilemma. Several methods for measuring DCIS exist, including clinical measurement, radiographic assessment, and gross pathologic assessment. Other methods have been employedfor this purpose, such as counting the number of tissue sections involved, direct measuring of DCIS from glass slides, and even counting the number of ducts involved. Furthermore, there is no consensus for assessing adequacy of margins. The myriad of techniques for quantifying DCIS has profound implications for treatment and for prognostic evaluation. The inherent difficulties in quantifying DCIS are multifactorial, and the need to establish a standardized approach for reporting the extent of DCIS by correlating radiographic, clinical, gross, and histologic findings is imperative.

Microinvasive carcinoma of the breast: can it be diagnosed reliably and is it clinically significant?

Deciding whether in-situ breast carcinoma is associated with microinvasion is a common problem. Histological features resembling invasion can be simulated by in-situ carcinoma distorted by inflammatory and reparative changes. Having expended the effort to diagnose genuine microinvasion, just how useful is this diagnosis in planning further treatment and follow-up? In the following articles, Hoda et al. comment on the utility of immunohistochemistry in resolving uncertainty about the presence of microinvasion, and Ellis et al. critically appraise the definition of microinvasion and its clinical significance.

Double immunolabeling with cytokeratin and smooth-muscle actin in confirming early invasive carcinoma of breast.

Histopathological identification of invasive breast carcinoma in its earliest phases is fraught with pitfalls. Preinvasive malignant lesions complicated by radial scar, sclerosing adenosis, and lobular cancerization, among other lesions, may simulate invasive carcinoma. Fibrosis, inflammatory reaction, and other stromal changes around in situ carcinoma may mask microinvasive foci on routine stains. Conventional immunohistochemistry to demonstrate basement membrane or myoepithelial cell layer may not, by itself, be unequivocally diagnostic of invasion. We performed a novel double immunoenzyme labeling technique using an avidin-biotin complex peroxidase-diaminobenzidine system for smooth-muscle actin followed by an alkaline phosphatase anti-alkaline phosphatase-new fuchsin system for cytokeratin antigen on formalin-fixed, paraffin-embedded histology sections to evaluate 32 such problematic cases. The initial histologic impression with hematoxylin and eosin staining alone was as follows-first group: microinvasive carcinoma-10; second group: carcinoma in situ--"stromal invasion cannot be ruled out"--15; third group: frankly infiltrating carcinoma of various grades and morphologic types-6. The last group served as positive control for invasion. One fibroadenoma with fine-needle-aspiration-induced artifact simulating stromal invasion was also included. The double immunoenzyme labeling technique imparted a dark brown color to the myoepithelial cells and a vivid red color to the epithelial cells, making individual or loosely cohesive groups of malignant epithelial cells infiltrating the stroma easily detectable, whereas their in situ counterparts were contained within dark brown myoepithelial boundaries. The TNM 1997 definition of pT1mic, i.e., extension of malignant cells in the stroma with no focus measuring >0.1 cm, was followed to classify microinvasion. In the first group, microinvasion was confirmed in six cases but was not demonstrable in four. In the second group, definite invasion was identified in five cases, ruled out in nine, and in one case the suspicion of early invasion could not be entirely ruled out even after double immunoenzyme labeling. Thus, it was possible to render a definite opinion regarding presence or absence of invasion in 24 of 25 (96%) cases diagnosed as or suspected to be microinvasive. The precise and simultaneous elucidation of topography between malignant cells and myoepithelial cells on a single permanent section makes this technique a useful diagnostic tool in the evaluation of those cases of breast carcinoma that exhibit equivocal invasion.

Appendiceal CT in 140 cases. Diagnostic criteria for acute and necrotizing appendicitis.

Computed tomography (CT) was performed in 140 patients with suspected acute appendicitis. Thin collimation (5 mm), intravenous contrast enhancement, 1-second scan times, and supplementary cecal air insufflation were emphasized. CT accuracy was 98% overall (137/140), and 99% in the 124 cases with early surgery. Necrotizing appendicitis was diagnosed by CT with 86% accuracy and 90% positive predictive value.