The challenging estrogen receptor-negative/ progesterone receptor-negative/HER-2-negative patient: a promising candidate for epidermal growth factor receptor-targeted therapy?

While epidermal growth factor receptor (EGFR)-targeted therapy has been very promising in a number of human malignancies, to date these targeted biologic agents have not proven effective in breast cancer. However, the EGFR tyrosinase inhibitors have been used indiscriminately against all types of breast tumors, perhaps missing a subpopulation of patients who may be prime candidates for EGFR-targeted therapy. In this communication we propose that patients with estrogen receptor (ER)-negative/progesterone receptor (PR)-negative/HER-2-negative tumors, which currently present a therapeutic challenge for the oncologist, may be the subgroup of breast cancer patients that might benefit from specific EGFR-targeted therapies.

Correlation of her-2/neu gene amplification with other prognostic and predictive factors in female breast carcinoma.

The purpose of this study was to determine if any relationship exists between Her-2/neu gene amplification and estrogen receptor (ER), progesterone receptor (PR), MIB-1, grade, size and age in female breast cancer. Five hundred and eighteen female patients with invasive breast carcinoma, 390 ductal and 128 lobular, in which assessment of Her-2/neu amplification by fluorescence in-situ hybridization (FISH) has been performed, were reviewed retrospectively. Each patient was further assessed for ER, PR, MIB-1, grade, size and age at diagnosis. Chi-square analysis was then used to correlate the above observations. Overall gene amplification was seen in 76 (15%) of the cases, 68 (17%) were ductal and 8 (6%) were lobular. Her-2/neu gene was amplified in 37 (10%) out of 379 ER positive cases and in 39 (28%) out of 139 ER negative cases. Her-2/neu was amplified in 22 (7%) out of 301 PR positive cases and in 54 (25%) out of 217 PR negative cases. Amplification occurred in 18 (8%) out of 222 negative MIB-1 cases and amplified in 58 (20%) out of 296 positive cases. Amplification was seen in 5 (10%) out of 49 grade I tumors, 17 (12%) out of 143 grade II tumors and 54 (27%) out of 198 grade III tumors. Lobular carcinomas were not graded. Amplification was present in 52 (15%) out of 346 T1 lesions, in 17 (13%) out of 130 T2 lesions, in 5 (17%) out of 30 T3 lesions and in 2 (17%) out of 12 T4 lesions. Her-2/neu was amplified in 67 (14%) out of 467 woman 41 years and older, and in 9 (18%) out of 51 women 40 years and younger. Comparison of these frequencies using chi-square test revealed statistically significant correlation between Her-2/neu amplification and ductal versus lobular carcinoma (p<0.0003), ER (p=0.0001) and PR (p<0.0001) negative tumors, over-expression of MIB-1 (p<0.0005) and high tumor grade (p=0.0009), while size of the tumor (p=0.08) and age of the patients (p=0.67) were not statistically significant. Correlation was found between Her-2/neu amplification and tumor type, high histological grade, ER and PR negative tumors, and high proliferative MIB-1 index. No correlation was found between size of the tumor and age of the patient with Her-2/neu amplification.

Kikuchi-Fujimoto disease: hydroxychloroquine as a treatment.

We describe a case of recurrent Kikuchi's disease in a South Asian-American man that was treated successfully with chloroquine and on recurrence with hydroxychloroquine. Each treatment led to a very prompt response.

Fine-needle aspiration of subcutaneous panniculitis-like T-cell lymphoma.

We report the fine-needle aspiration (FNA) cytology findings of Subcutaneous Panniculitis-like T-cell Lymphoma (SCPTCL) in a 66-year-old woman who presented with a four month history of asymptomatic subcutaneous nodules on her right chest wall and back. An excisional biopsy of the right chest nodules was performed, and the diagnosis of SCPTCL was rendered. On a follow-up visit, several skin lesions were noted throughout her body. A fine-needle aspiration (FNA) of the right inguinal region was performed. The FNA yielded cellular smears, composed mainly of sheets of epithelioid histiocytes and scattered multinucleated cells. However, no distinct granulomas were noted. The background of the cytological smears showed scattered atypical lymphoid cells, some of which displayed nuclear membrane irregularities. To the best of our knowledge, the cytological features on FNA material of SCPTCL have not been described.

Splenic fine needle aspiration and core biopsy. A review of 49 cases.

OBJECTIVE: To analyze the authors' experience with splenic fine needle aspiration (sFNA) and splenic core biopsy (sCB) and to examine their roles in patients with splenomegaly or splenic mass lesions. STUDY DESIGN: A total of 56 sFNAs and/or sCBs were performed on 49 patients for neoplastic and nonneoplastic indications. Both sFNAs and sCBs were performed in 21 (38%) cases, sFNAs alone in 26 (46%) and sCBs only in 9 (16%). Cytologic findings were evaluated for specimen adequacy, diagnosis and use of ancillary techniques. Cytologic diagnosis was compared with histology on subsequent splenectomy or bone marrow biopsy, when available. RESULTS: There were a total of 33 males and 16 females (aged 30-82 years) in the study. Radiologic findings were single or multiple masses (42), fluid collection (3) or diffuse splenomegaly (4). The cytologic diagnosis was neoplastic process in 12 (25%), nonneoplastic in 32 (65%) and inadequate specimen in 5 (10%). The procedure was adequate for diagnosis in 44 (90%) patients. Cytologic diagnosis correlated with subsequent histology in all cases where tissue diagnosis was available. Major complications occurred in 3 (6%) patients, including hemorrhage, pseudoaneurysm and hypotension. Five other patients (10%) had minor complications. The number of passes, inclusion of sCB and repeat procedures were not associated with an increased risk of complications. CONCLUSION: sFNA and sCB have excellent diagnostic accuracy in both neoplastic and nonneoplastic splenic disorders. While the overall complication rate is significant, major complications of the procedure are uncommon.

Fine-needle aspiration of superficial and deeply seated lymph nodes on patients with and without a history of malignancy: review of 439 cases.

This study addresses the utility of fine-needle aspiration (FNA) in assessing lymphadenopathy in patients with and without a previous history of malignancy. We reviewed the FNAs of superficial and deeply seated lymph nodes performed at our institution over a period of 18 yr (1983-2001). Where applicable, we also reviewed and report here the results of subsequent surgical excisional biopsies. We analyzed data from 439 patients, who ranged in age from 1 to 90 yr. The neck and retroperitoneum were the most frequently sampled sites (47% and 25%, respectively). Among the 439 FNAs, adequate material was obtained in 421 cases (96%); the remaining 18 were unsatisfactory (4.1%). Malignant diagnoses were rendered in 330 cases (75% of 439), four were suspicious for lymphoma (0.9%), and 87 were read as reactive lymph nodes or granulomas (20%). The most common malignant cytologic diagnoses from these lymph node FNAs were adenocarcinoma, squamous cell carcinoma, and lymphoma. We compared results between two major groups: patients with a history of malignancy and those without. FNA showed malignancy in 87% of patients with a history of cancer and 41% without such a history. Thirty-three or 10% of patients with a history of malignancy were given a benign diagnosis and follow-up surgical excisional biopsies were performed in nine of these cases. Four of the nine showed low-grade lymphoma. Of the 18 non-diagnostic FNAs, nine came from patients with a history of malignancy and in six of these nine who had a follow-up surgical excisional biopsy the lymph nodes were positive for malignancy. Of the other nine, who had no history of malignancy, only two had follow-up biopsies and both of these were negative. Patients with a history of malignancy are more than twice as likely to show malignancy on lymph node FNA compared to those without such a history (87% vs. 41%). Knowing whether a patient has a history of malignancy provides the appropriate level of suspicion for ordering ancillary investigations or even recommending excisional biopsy for further evaluation.

Assessment of Her-2/Neu status by immunohistochemistry and fluorescence in situ hybridization in mammary Paget disease and underlying carcinoma.

HER-2/Neu overexpression is seen in 20% to 30% of invasive breast carcinomas and has been reported in as many as 80% of high-grade infiltrating carcinomas. Earlier studies have suggested that 100% of the tumor cells in mammary Paget disease show overexpression of HER-2 protein. We undertook this study to assess HER-2 status of mammary Paget disease and of the underlying breast carcinoma, when present, by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Formalin-fixed, paraffin-embedded tissue from 20 cases of mammary Paget disease were analyzed for HER-2 status by IHC and FISH. IHC for estrogen receptor (ER) was also performed. The patients ranged in age from 34 to 88 years, with a mean age of 62 years. Eighty percent of the cases showed strong overexpression (3+) of HER-2 protein by IHC, and all of these cases showed more than 5-fold amplification of the HER-2 gene by FISH. The remaining 4 cases, which were negative for HER-2/Neu by IHC, showed no amplification by FISH. All of the latter cases expressed ER, whereas no case that overexpressed HER-2 expressed ER. Sixteen cases had an underlying tumor, which was in situ in 6 cases. The underlying tumors were identical to the Paget disease with respect to their HER-2/Neu overexpression by both IHC and FISH. HER-2 overexpression was identified in 80% of our cases of Paget disease. There was 100% concordance between HER-2 protein overexpression by immunohistochemistry and gene amplification in both the Paget and the underlying tumor. Moreover, all of the cases negative for HER-2 overexpression expressed ER, whereas those positive for HER-2 did not.

Fine-needle aspiration of clinically suspicious palpable breast masses with histopathologic correlation.

BACKGROUND: The purpose of this study was to compare the diagnostic accuracy of fine-needle aspiration (FNA) of clinically suspicious palpable breast masses in women younger and older than 40 years of age. METHODS: All women who had FNA biopsy with subsequent tissue biopsy were included. The cytologic diagnoses were classified into three groups: malignant, suspicious, or benign. Histopathologic correlation was based on either a needle core biopsy, an excisional biopsy, or a mastectomy specimen. RESULTS: A total of 1,158 fine-needle aspirations performed between 1982 and 2000, on women being evaluated for a clinically palpable breast mass were included in the study. The patients were divided into two groups: group I consisted of 231 patients aged 40 years and younger, and group II consisted of 927 patients aged 41 years and older. In group I there were 117 (51%) malignant FNA diagnoses, and only 1 (1%) false-positive case, subsequently diagnosed on histopathologic material as an atypical papillomatosis. There were 20 (9%) cases diagnosed as suspicious on FNA. On histopathology 10 were malignant, and 10 were benign. Of the 91 (39%) cases interpreted as benign, only 1 (1%) was a false negative. In group II, which comprised 927 patients, there were 693 (74%) malignant FNA diagnoses, and 3 (less than 1%) false-positive cases, which on follow-up histopathologic examination revealed 2 atypical ductal hyperplasias and 1 atypical papilloma. There were 90 (10%) cases diagnosed as suspicious on FNA. On histopathology, 68 were malignant and 22 were benign. Of the 131 (14%) lesions interpreted as benign, there were 18 false-negative cases (14%), which included 17 infiltrating carcinomas and 1 ductal carcinoma in-situ. Twelve (1%) of the cases were inadequate for the study. CONCLUSIONS: The sensitivity, specificity, and positive predictive values were remarkably high and comparable in both groups: group I had 99% sensitivity, 99% positive predictive value, 99% specificity, and 99% negative predictive value; and group II had 98% sensitivity, 97% specificity, 99% positive predictive value, and 86% negative predictive value. The overall rate of false-positive (less than 1%) and false-negative cases (9%) is comparable with published literature. Suspicious cases should be further evaluated, as our study revealed more than 50% to be malignant. The incidence of malignancy in patients presenting with a clinically palpable breast mass with follow-up biopsy was 51% in patients aged 40 years and younger and 74% in patients aged 41 years and older. Fine-needle aspiration is an excellent diagnostic tool in assessing clinically palpable breast masses.