Atypia in fine needle aspirates of breast lesions.

BACKGROUND: The atypical category is controversial in fine needle aspiration cytology (FNAC) of the breast; most are benign, but a significant number are malignant. To date, no morphological criterion has been found to be consistent in predicting malignancy. AIMS: To evaluate specific cytological parameters and assess their usefulness in predicting histological outcome in a cohort of atypical breast FNAC, in order to establish a set of objective criteria in defining 'high risk' atypical breast FNAC. METHODS: A retrospective review of 98 cases of atypical breast FNAC with histological correlation was undertaken. The cytological preparations were evaluated for cellularity, percentage of epithelial cell cluster and single epithelial cells, nuclear atypia, nucleus:cytoplasm ratio, percentage of bipolar nuclei, and the presence of stromal fragments, histiocytes and necrosis. RESULTS: 66 of 98 cases (67.35%) showed benign histology and 32 cases (32.65%) showed malignant histology. Compared with the malignant group, the benign group had significantly lower patient age (p=0.05), higher bipolar nuclei (p<0.0001), less degree of nuclear pleomorphism (p<0.0001), lower nucleus:cytoplasm ratio (p<0.0001), lower cellularity (p=0.05) and less necrosis (p<0.001). There was no difference in the percentage of epithelial clusters and single cells, or the presence of stromal fragments and histiocytes. CONCLUSIONS: The presence of nuclear pleomorphism, high nucleus:cytoplasm ratio, epithelial cell atypia, low number of bipolar nuclei and necrosis are useful parameters to predict malignancy in atypical FNAC of the breast. Assessment of these factors in atypical FNAC may be helpful in predicting cancer risk and subsequent management decision making.

Papillary lesions of the breast--accuracy of core biopsy.

AIMS: To assess the accuracy of diagnosing papillary breast lesions in core needle biopsy. METHODS AND RESULTS: One hundred biopsy specimens of papillary breast lesions were reviewed and compared with the final excisional diagnoses. The discordant biopsy specimens were stained for oestrogen receptor (ER), cytokeratin (CK) 14 and p63, and these specimens were reclassified based on these results. The overall core biopsy accuracy, false-positive and false-negative rate were 79%, 5% and 16%, respectively. A benign core biopsy specimen diagnosis gave a false-negative rate of 10%, and malignant core biopsy specimen diagnosis did not give any false-positive results. Using homogeneous ER (epithelial), positive CK14 (epithelial) and p63 (myoepithelial) immunoreactivity as benign criteria, the discordant rate was reduced by 30% and 69% when using all three or two of these three criteria for diagnosis. However, false-positive and -negative cases could not be totally eliminated. CONCLUSIONS: Immunohistochemistry is helpful in core biopsy diagnosis of papillary breast lesions, but some cases remained misdiagnosed.

Predictors of invasion in needle core biopsies of the breast with ductal carcinoma in situ.

A significant proportion of ductal carcinomas in situ (DCISs) of the breast diagnosed on core biopsies had invasion upon excision. An assessment of various invasion predictors in the biopsies yielded conflicting results. A cohort of 157 cases with needle core biopsy diagnosed with DCISs (including 109 histologically proven DCISs, and 48 cases with invasion upon excision) were evaluated for the numbers of positive and total cores, the percentage of positivity, lobular cancerization, tumor nuclear grade, necrosis, calcification, predominate histological pattern, lymphocytic infiltrate and excisional tumor size. The mean positive core percentage and excisional tumor size were 76% and 2.8 cm for invasive and 66% and 1.9 cm for noninvasive groups. In the biopsy of the invasive group, cancerization of lobules was present in 52%, and nuclear grades 1, 2 and 3 were present in 31, 31 and 38%, respectively. Large comedo and small noncomedo necroses were present in 48 and 10%, whereas large and small calcifications were present in 16 and 21%. Solid, cribriform and papillary patterns were observed in 88, 38 and 21%, respectively. Moderate to marked lymphoid infiltrate was present in 31%. In the biopsy of the noninvasive group, cancerization of lobules was present in 69%, and the nuclear grades 1, 2 and 3 were present in 23, 48 and 29%, respectively. Large comedo and small noncomedo necroses were present in 35 and 11%, whereas large and small calcifications were present in 33 and 23%. Solid, cribriform and papillary patterns were observed in 85, 39 and 9%, respectively. Moderate to marked lymphoid infiltrate was present in 36%. Comparing these groups, a higher positive core percentage, papillary pattern and less cancerization of lobules in the cores and larger excisional tumor size were associated with a higher chance of invasion. Calcification, necrosis and nuclear grade were not significant invasion predictors.

The role of conservative treatment in idiopathic granulomatous mastitis.

Idiopathic granulomatous mastitis (IGM) is a rare benign inflammatory disease of the breast that mimics carcinoma of the breast. Its etiology and treatment remain unclear. A retrospective review of nine women with histopathologic diagnosis of IGM was performed. The women had a mean follow-up of 18.7 months and a mean age of 45.7 years (range 32-83 years). The main presentation was breast mass (100%). Clinically and radiologically, 55.6% of the women were suspected to have malignancy. One patient was treated with lumpectomy without recurrence. Eight patients were treated with expectant management with close regular surveillance. No surgery was performed and no medications were given. Fifty percent of the patients had spontaneous complete resolution of disease after a mean interval of 14.5 months. These four patients had no recurrence. Fifty percent of patients had static disease. In conclusion, it is important to differentiate IGM from carcinoma of the breast. Tissue biopsy remains the gold standard to confirm the diagnosis. Expectant management with close regular surveillance is the treatment of choice.

Granulomatous mastitis: a clinicopathological review of 26 cases.

AIMS: Twenty-six cases of granulomatous mastitis were examined to determine the common histological and clinical features and the possible association with micro-organisms. METHODS: A retrospective review of the clinical and histological features of these cases was undertaken, including granuloma, inflammatory cell infiltrate, multinucleated giant cells, necrosis and lymphocytic lobulitis, as well as special stains for micro-organisms including Mycobacterium, other bacteria and fungus. PCR for Mycobacterium tuberculosis DNA was also performed in 19 cases. RESULTS: Granulomas were present in all cases (100%) while multinucleated giant cells were seen in 17 cases (65%), background inflammatory cell infiltrate in 23 cases (88%), predominantly lymphocytes in 18 cases (69%), significant lymphocytic lobulitis in 13 of 19 cases (68%) and necrosis in three cases (11%). Special stains and cultures for micro-organisms were all negative. Clinically, four cases (15%) were associated with duct ectasia, eight (31%) with abscess, and there was no such association in 14 cases (54%). Of the 19 cases with PCR for tuberculosis, one case showed Mycobacterium DNA in the sample, raising the possibility of occult tuberculosis infection. CONCLUSIONS: Granulomatous mastitis is a heterogeneous group of diseases with a diverse clinical picture and association. Most idiopathic cases are not associated with specific micro-organisms.

Quantitative analysis of cell-free Epstein-Barr virus DNA in plasma of patients with nonnasopharyngeal head and neck carcinomas.

PURPOSE: We investigated the detectability of EBV DNA in the plasma of patients with non-nasopharyngeal head and neck carcinomas (NNHNC). Previous studies have shown that EBV is present in the tumor tissue of some NNHNC. EXPERIMENTAL DESIGN: We recruited 101 patients with NNHNC and 48 healthy controls. Blood samples were taken from controls and patients before treatment. Tumor tissue samples were tested for the presence of EBV in the first 69 patients by in situ hybridization for small EBV-encoded RNA (EBER). Plasma EBV DNA was measured by real-time quantitative PCR in patients and controls. RESULTS: Squamous cell carcinoma (SCC) was the commonest histology (78 patients) followed by lymphoepithelial carcinoma (8 patients). EBER was detected in tumor cells in 7 of 69 patients tested. All of the EBER-positive tumors were lymphoepithelial carcinoma. Two controls (2 of 48; 4.2%) had detectable plasma EBV DNA. Plasma EBV DNA was detected in all of the patients with EBER-positive tumors, and in 23 of 94 (24.5%) patients with tumors of EBER-negative or unknown status. The proportion of plasma EBV DNA-positive cases in either group was significantly higher than that in the control group (P < 0.0027). Plasma EBV DNA concentrations in patients with EBER-positive tumors (median, 3827 copies/ml) were significantly higher than those in the controls (median, 0 copy/ml; P = 0.0001). Of patients with SCC, 21 (26.9%) had detectable plasma EBV DNA (median concentration, 34 copies/ml). Plasma EBV DNA concentrations in the whole group of patients with SCC (median, 0 copy/ml; interquartile range, 0-4 copies/ml) were also significantly higher than those in the controls (P = 0.001). CONCLUSIONS: Our data indicate that plasma EBV DNA reflects tumoral EBER status, and it may be of use as a tumor marker for EBER-positive NNHNC. The biological and clinical significance of low levels of circulating EBV DNA in the minority of patients with EBER-negative tumors remain to be elucidated.

Neuroendocrine differentiation in pure type mammary mucinous carcinoma is associated with favorable histologic and immunohistochemical parameters.

Mucinous carcinoma of the breast is a specific good prognostic type malignancy occurring in elderly patients. Neuroendocrine differentiation has long been described in mucinous carcinoma, but the significance of such finding is uncertain. We evaluated the neuroendocrine differentiation profiles of 38 cases of pure mucinous carcinoma and compared the clinicopathological differences between those with and those without neuroendocrine differentiation. The parameters assessed included patients' age, tumor size, nuclear grade, axillary lymph node status at time of diagnosis, percentage area of intratumoral mucin, and the expression of estrogen and progesterone receptors, cerbB2 oncoprotein, and three neuroendocrine markers, namely neurone-specific enolase, chromogranin, and synaptophysin by immunohistochemistry. Patients' outcome and follow-up period were also documented. Of the 38 cases of pure mucinous carcinoma, 28, 11 and six cases showed positive staining for 1, 2 and 3 of the neuroendocrine markers. For all the groups with variable neuroendocrine differentiation and compared to those without such differentiation, they all showed older patients' age, higher proportion of tumors with lower nuclear grade, lower incidence of axillary lymph node metastasis, a higher progesterone receptor, and lower cerbB2 oncoprotein expression. No difference was detected between tumor size, intratumoral mucinous area, and estrogen receptor status. In all, 37 patients did not have distant metastases or local recurrences at the end of follow-up period, while one patient with coexisting high-grade ductal carcinoma in situ at time of diagnosis died of breast carcinoma. Our findings suggest that the identification of neuroendocrine differentiation in pure mucinous carcinoma is associated with more favorable histologic and immunohistochemical parameters.

Nasopharyngeal granulomatous inflammation and tuberculosis complicating undifferentiated carcinoma.

OBJECTIVE: Four cases of nasopharyngeal granulomatous inflammation after radiotherapy for undifferentiated carcinoma were analyzed for tuberculosis, and the histologic features were compared. STUDY DESIGN AND SETTING: We conducted a retrospective study with analysis of tuberculosis by Ziehl Neelsen staining and polymerase chain reaction analysis for Mycobacterium tuberculosis DNA on histologic materials. RESULTS: Three patients had previous nasopharyngeal undifferentiated carcinoma, one had previous metastatic undifferentiated carcinoma to cervical lymph nodes, and all patients received similar radiotherapy regimen. The light microscopic features were similar with epithelioid histiocytes and granulomas with Langhan's giant cells. In 3 cases, acid-fast bacilli were identified by Ziehl Neelsen stain, and 1 was negative. The results of 2 cases were confirmed by polymerase chain reaction analysis for Myocbacterium tuberculosis DNA. CONCLUSION: Granulomatous reaction after radiotherapy of nasopharyngeal undifferentiated carcinoma can be caused by tuberculosis. SIGNIFICANCE: Diligent search for organisms in postirradiation granulomatous inflammation is warranted to avoid missing an occult tuberculosis infection.

Tuberculosis of the nasopharynx: a rare entity revisited.

OBJECTIVES: Tuberculosis of the nasopharynx is uncommon. A large series of 17 cases is reported, and the clinical and pathological features are discussed. STUDY DESIGN: A retrospective review. METHODS: Seventeen archived cases of biopsy-proven nasopharyngeal tuberculosis were reviewed for patient age and sex, presenting complaint and duration, systemic symptoms, cervical lymphadenopathy, and chest x-ray findings. These findings were compared with a compilation of 40 cases reported in the English literature. RESULTS: There was a female predominance (13 women and 4 men), with age range of 20 to 74 years (mean age, 38 y). The most common presentation was enlargement of the cervical lymph nodes (53%), followed by hearing loss (12%), tinnitus, otalgia, nasal obstruction, and postnasal drip (6% each). The duration of the presenting symptoms ranged from 1 week to 1 year (mean duration, 16 wk). Ten patients (59%) had cervical lymphadenopathy, two (12%) had systemic symptoms (fever, weight loss, night sweats), and one patient (6%) had miliary pulmonary tuberculosis. Direct endoscopic examination showed nasopharyngeal mucosal irregularity or mass in the majority of patients (12 patients [70%]). These features were similar to those reported in the literature. CONCLUSIONS: Nasopharyngeal tuberculosis is uncommon, usually occurring without pulmonary or systemic involvement. Cervical lymphadenopathy occurs in more than half of the patients and is the most common presenting complaint; this, together with the nasopharyngeal findings of mass or mucosal irregularity, makes differentiation from carcinoma on clinical examination difficult, necessitating histological evaluation.

Fine needle aspiration cytologic features of mammary phyllodes tumors.

OBJECTIVE: To evaluate specific diagnostic fine needle aspiration cytologic (FNAC) features of phyllodes tumor (PT), particularly in the differentiation from fibroadenoma (FA). STUDY DESIGN: Twenty-eight FNAC of PT were reviewed for smear cellularity, epithelial and stromal fragments, their size and atypia, epithelial/stromal area ratio, background single stromal cells (oval or columnar), multinucleated giant cells, and squamous and apocrine cells. Twenty-one FNAC of fibroadenoma were also assessed for comparison. RESULTS: PT was significantly larger than FA. Epithelial fragments were found in all cases, with atypia present in PT. Stromal fragments were present in half the cases; there was no difference in stromal size, but the epithelial/stromal area ratio was significantly lower in PT than FA. Single columnar stromal cells with recognizable cytoplasm and multinucleated stromal giant cells were seen in some PT but not in FA. CONCLUSION: Cytologic diagnosis of PT remains difficult, with significant overlap with FA. The presence of large size, low epithelial/stromal ratio, epithelial atypia, columnar stromal cells with visible cytoplasm and stromal giant cells favors a diagnosis of PT over FA.