The role of immunohistochemistry for smooth-muscle actin, p63, CD10 and cytokeratin 14 in the differential diagnosis of papillary lesions of the breast.

BACKGROUND: Histological differentiation of mammary papillary lesions can be difficult. The evaluation of myoepithelial cells can be helpful, with benign papilloma showing a continuous myoepithelial cell layer, which becomes attenuated or absent in malignant papillary lesions. METHODS: A large series of 100 papillomas (28 papillomas with florid epithelial hyperplasia) and 68 papillary carcinomas (9 invasive, 44 in situ, and 15 ductal carcinomas in situ (DCIS) involving papillomas) of the breast were stained for myoepithelial cells by immunohistochemistry using antibodies to smooth-muscle actin (SMA), p63, CD10 and cytokeratin (CK) 14. RESULTS: In the papillomas, using these four antibodies, myoepithelial cells were positive in 88%, 99%, 91% and 95% of cases, respectively, with SMA showing marked stromal component cell staining and CD10 showing epithelial and stromal staining. CK14 also showed epithelial staining in 71% of papillomas and 96% of papillomas with florid epithelial hyperplasia. In the papillary carcinomas, 36 (53%) cases showed staining of myoepithelial cells that were scattered, discontinuous and diminished in number and the remaining 32 (47%) cases did not show myoepithelial cells. Invasive papillary carcinoma has the lowest proportion (33%) with myoepithelial cells, and DCIS involving papillomas had the highest proportion (87%). CONCLUSIONS: p63 had the highest sensitivity and did not cross-react with stromal cells and only rarely with epithelial cells. CK14 has the added ability to distinguish between florid epithelial hyperplasia involving papilloma and DCIS involving papillomas. CK14 and p63 may be used as an adjunct in assessing difficult papillary lesions of the breast.

Metaplastic carcinoma of the breast: a clinicopathological review.

BACKGROUND: Mammary metaplastic carcinoma encompasses epithelial-only carcinoma (high-grade adenosquamous carcinoma or pure squamous cell carcinoma), biphasic epithelial and sarcomatoid carcinoma and monophasic spindle cell carcinoma. AIM: To evaluate the clinicopathological features of a large series of 34 metaplastic carcinomas. METHODS: 10 epithelial-only, 14 biphasic and 10 monophasic metaplastic carcinomas were assessed for nuclear grade, hormone receptor status, HER2/neu (cerbB2) oncogene expression, Ki-67 and p53, lymph node status and recurrence on follow-up. RESULTS: Intermediate to high nuclear grade were assessed in most (33/34) tumours. Oestrogen and progesterone receptors were negative in 8 of 10 epithelial-only, all 14 biphasic, and 9 of 10 monophasic tumours, cerbB2 was negative in 7 of 10 epithelial-only, all 14 biphasic and 8 of 10 monophasic tumours. Ki-67 was found to be positive in 6 of 10 epithelial-only, 6 of 14 biphasic, and 7 of 10 monophasic tumours, whereas p53 was positive in 6 of 10 epithelial-only, 7 of 14 biphasic, and 8 of 10 monophasic tumours. Lymph node metastases were seen in 7 of 7 epithelial-only, 7 of 11 biphasic, and 3 of 7 monophasic tumours. Recurrences were seen in 4 of 7 epithelial-only, 8 of 9 biphasic, and 4 of 9 monophasic tumours. CONCLUSIONS: All three subtypes of metaplastic carcinoma are known to behave aggressively, and should be differentiated from the low-grade fibromatosis-like metaplastic carcinoma, which does not metastasize. Oncological treatment options may be limited by the frequently negative status of hormonal receptor and cerbB2.

CD44s is useful in the differentiation of benign and malignant papillary lesions of the breast.

BACKGROUND/AIMS: CD44s, the standard form of CD44, has been shown to be downregulated during malignant transformation of breast cancers. It has also been reported recently to be a useful marker in differentiating between benign and malignant papillary lesions of the breast, with high expression in the former. CD44s expression in benign and malignant papillary lesions was evaluated. METHODS: CD44s expression was assessed by immunohistochemistry in 101 benign papillomas and 59 papillary carcinomas (seven invasive papillary carcinomas, 41 papillary ductal carcinomas in situ, and 11 ductal carcinomas involving papillomas). RESULTS: Patients' age and tumour size were significantly different between the papilloma and papillary carcinoma groups (p < 0.0001). CD44s showed positive staining in 45 papillomas (45%) and five papillary carcinomas (8%), and the difference was significant (p < 0.0001). The myoepithelial cells, when present, were also positive for CD44s in both groups, with no observable differences. Using CD44s positive staining to differentiate between benign and malignant papillary lesions gives a sensitivity, specificity, and accuracy of 45%, 92%, and 62%, respectively. CONCLUSIONS: CD44s may be useful as an adjunct in the evaluation of morphologically problematic cases of papillary lesion of the breast.

Stromal CD10 expression in mammary fibroadenomas and phyllodes tumours.

BACKGROUND/AIMS: CD10 (CALLA) has recently been reported to be expressed in spindle cell neoplasia, and has been used to differentiate endometrial stromal sarcoma from leiomyoma and leiomyosarcoma. In the breast, myoepithelial cells express CD10, but there are few studies of the expression of CD10 in mammary fibroepithelial lesions. METHODS: Stromal CD10 expression was studied in 181 mammary phyllodes tumours (102 benign, 51 borderline malignant, and 28 frankly malignant) and 33 fibroadenomas using immunohistochemistry, to evaluate whether differences in expression correlated with the degree of malignancy. RESULTS: There was a progressive increase in the patients' age and tumour size, from fibroadenoma to phyllodes tumours with an increasing degree of malignancy (p < 0.001). Stromal CD10 expression was positive in one of 33 fibroadenomas, six of 102 benign phyllodes tumours, 16 of 51 borderline malignant phyllodes tumours, and 14 of 28 frankly malignant phyllodes tumours. The difference was significant (p < 0.001) and an increasing trend was established. Strong staining was seen in subepithelial areas with higher stromal cellularity and activity. Stromal CD10 expression had a high specificity (95%) for differentiating between benign lesions (fibroadenomas and benign phyllodes tumours) and malignant (borderline and frankly malignant) phyllodes tumours. CONCLUSIONS: CD10 may be a useful adjunct in assessing malignancy in mammary fibroepithelial lesions.

Stromal nitric oxide synthase (NOS) expression correlates with the grade of mammary phyllodes tumour.

BACKGROUND: Nitric oxide synthase (NOS), particularly endothelial and inducible forms (e/i-NOS), are expressed in various cancers, including breast cancer. In mammary fibroepithelial lesions, NOS expression in stromal cells has been reported to be lower in fibroadenomas than in phyllodes tumours. AIMS: To investigate NOS expression in phyllodes tumours of varying degrees of malignancy. METHODS: One hundred and sixty seven mammary phyllodes tumours (97 benign, 47 borderline malignant, and 23 frankly malignant) were evaluated for e-NOS and i-NOS expression by immunohistochemistry. Correlations with previously reported expression of stromal vascular growth factor (VEGF) and microvessel density were also performed. RESULTS: Stromal expression of e-NOS was absent, weak, moderate, and strong in 43%, 31%, 13%, and 13% of benign tumours; 17%, 26%, 13%, and 44% of borderline malignant tumours; and 17%, 35%, 13%, and 35% of frankly malignant tumours, respectively. Stromal expression of i-NOS was 77%, 18%, 4%, and 1% in benign tumours; 42%, 28%, 19%, and 11% in borderline malignant tumours; and 43%, 13%, 26%, and 18% in frankly malignant tumours, respectively. Stromal expression of both i-NOS and e-NOS was significantly different between the benign and malignant (borderline and frank) groups of phyllodes tumours (p < 0.0001). Furthermore, the expression of i-NOS correlated with stromal VEGF expression and microvessel density. The expression of NOS in the epithelial cells was strong, and showed no differences between the different groups of tumours. CONCLUSIONS: Higher stromal expression of NOS in phyllodes tumours is associated with malignancy, suggesting a possible role in malignant progression, particularly metastasising potential.

Ductal carcinoma in situ arising in mammary hamartoma.

Hamartoma of the breast is an uncommon lesion. Although it can possess characteristic radiological features, the pathological appearance is not distinctive. Hamartoma is generally considered benign, but four cases have been reported with ductal and lobular carcinoma arising in hamartomas. This report describes further cases of hamartoma from which ductal carcinoma in situ arose, with one showing early invasion. In both cases, the tumours were within the hamartomas and were adequately excised during lumpectomies of the hamartomas, and the patients were well afterwards. This report emphasises the importance of adequate sampling of mammary hamartoma.

Fine needle aspiration cytology of granulomatous mastitis.

AIMS: Granulomatous mastitis (GM) is an uncommon breast lesion that mimics carcinoma. The fine needle aspiration cytological (FNAC) features of GM have rarely been discussed in the literature. These features are reported in eight histologically confirmed cases of GM. METHODS: A retrospective study was undertaken in which a diagnosis of GM had been made on histopathology, and the FNAC slides were reviewed and assessed for the presence of granulomas, necrosis, multinucleated giant cells, and inflammatory background cells. Polymerase chain reaction (PCR) for Mycobacterium tuberculosis was performed on the histological material to exclude tuberculosis. RESULTS: All cases were confirmed histologically and PCR for mycobacterial DNA was negative. In the FNACs, varying numbers of granulomas composed of epithelioid histiocytes were present in four cases. The same four cases showed giant cells of either foreign body or Langhan's type. No necrosis was noted. Six cases showed many histiocytes, some plump and others epithelioid, in the background. The number of epithelioid histiocytes corresponded to the presence of granulomas. Neutrophils were the predominant background inflammatory cells in most cases (six). CONCLUSIONS: The cytological diagnosis of GM is difficult because the features overlap with other aetiologies, including tuberculosis. Specific features are absent. The absence of necrosis and a predominantly neutrophilic infiltrate in the background favour a diagnosis of GM. This diagnosis should also be considered when abundant epithelioid histiocytes are seen in smears, even in the absence of granulomas. However, the definitive diagnosis of GM depends on histology from fine needle biopsies and negative microbiological investigations.

Hamartoma of the breast: a clinicopathological review.

AIMS: To review 25 cases of breast hamartoma and discuss the pathological criteria, and the usefulness of imaging modalities, fine needle aspiration cytology (FNAC), and needle core biopsy in the diagnosis. METHODS: The hamartomas were assessed for interlobular fibrotic stroma, stromal adipose tissue content, pseudo-angiomatous stromal hyperplasia, and epithelial changes (hyperplasia, adenosis or apocrine metaplasia, and cyst formation). All imagings, previous FNACs, and biopsies were also reviewed. RESULTS: Imaging (mammography, ultrasound, and magnetic resonance imaging) was performed in 18 cases, and mostly showed encapsulated masses with a heterogeneous appearance. Microscopically, all hamartomas demonstrated good demarcation with fibrous tissue condensation. Adipose tissue was noted in all cases (5-90%; mean, 31%), and interlobular fibrosis in 21 cases. Benign epithelial hyperplasia occurred in 10 cases, and pseudo-angiomatous stromal hyperplasia or cystic ducts in eight cases each. Apocrine metaplasia, calcification, stromal giant cells, and adenosis occurred in four cases or less. Two cases showed coexisting ductal carcinoma in situ limited to within the hamartoma. Needle core biopsies (four cases) and FNAC (14 cases) were largely insufficient, inconclusive, or non-specific. CONCLUSIONS: Hamartomas do not possess specific diagnostic histological features. The role of FNAC and needle core biopsy in making the diagnosis is limited, and requires clinical and radiological correlation to avoid underdiagnosis.

Non-operative management of small cell carcinoma of esophagus.

Primary small cell carcinoma of the esophagus (SmCC) is an uncommon aggressive tumor characterized by early systemic dissemination and poor prognosis, regardless of the methods of treatment. The optimal treatment strategy remains uncertain. A retrospective study was conducted to review the results of non-operative treatment for patients with limited and metastatic esophageal SmCC. Between 1993 and 2003, 10 patients were diagnosed to have primary esophageal SmCC in our institution. Six of them had disseminated diseases, whereas the other four had limited disease upon diagnosis. All patients were managed non-operatively by either chemotherapy and/or radiotherapy. The overall median survival was 8 months (range, 2-62 months). The survival was 4-62 months for patients with limited disease, whereas it was 2-10 months for patients with disseminated disease at initial diagnosis. In summary, the current study demonstrated satisfactory palliation could be achieved with chemo-radiation for patients with limited disease; however, the ultimate role of primary chemo-radiation for esophageal SmCC must await results from randomized trials.

Routine use of laparoscopic repair for perforated peptic ulcer.

BACKGROUND: Laparoscopic repair of perforated peptic ulcer was reported in 1990 but has not gained wide acceptance. The aim of this study was to evaluate the safety and efficacy of laparoscopic repair for perforated peptic ulcer in routine clinical practice. METHODS: This was a prospective analysis of 172 patients who underwent laparoscopic repair of a perforated peptic ulcer between July 1997 and June 2003. RESULTS: One hundred and seventy-two patients of mean age 54 (range 14-93) years had perforated peptic ulcer diagnosed by laparoscopy. There were 172 duodenal ulcers, 22 prepyloric and 13 non-juxtapyloric gastric ulcers. One hundred and sixty-five patients underwent omental patch closure of perforations; there were six Pólya gastrectomies and one ulcerectomy. Thirty-seven patients (21.5 per cent) required conversion to laparotomy. The mean operating time was 64.8 (range 14-180) min. The median postoperative requirement for intramuscular pethidine was one dose. The median postoperative hospital stay was 6 days. Complications occurred in 28 patients (16.3 per cent) resulting in three reoperations. Six patients with intra-abdominal collections were managed by percutaneous drainage. Two patients who underwent conversion developed a wound infection. Fourteen patients (8.1 per cent) died, 11 of whom were American Society of Anesthesiologists grade III and IV. CONCLUSION: Laparoscopic repair of perforated peptic ulcer is a safe emergency procedure in routine clinical practice for patients with perforated pyloroduodenal ulcer.