Fine-needle aspiration of a metaplastic breast carcinoma with extensive melanocytic differentiation: a case report.

Metaplastic carcinomas of the breast are uncommon breast tumors with aberrant cellular differentiation, most commonly showing ductal, squamous, and mesenchymal components. A breast carcinoma composed of both epithelial and melanocytic differentiation is rare, with only four previously reported cases in the literature. We present the fifth reported case, where the diagnosis was suggested by fine-needle aspiration (FNA) and later confirmed after the surgical specimen was excised. Histologically, this neoplasm revealed multidirectional differentiation, consisting primarily of squamous and melanocytic cell types, with focal glandular and osseous metaplasia. Based on the morphologic, immunohistochemical, and ultrastructural findings, we conclude that such tumors fall within the spectrum of metaplastic carcinomas of the breast. We believe that this case will further contribute to the understanding of this enigmatic tumor.

Lack of utility in clinical practice of cytologic examination of nonbloody cyst fluid from palpable breast cysts.

OBJECTIVE: This study was undertaken to answer the following question: Does cytologic evaluation of nonbloody fluid aspirated from breast cysts contribute to appropriate clinical management? STUDY DESIGN: A retrospective review of palpable breast cyst fluid cytologic reports and associated medical records was undertaken to determine whether the cytologic findings affected patient management. Breast cyst size, fluid volume, fluid color, and patient age were abstracted from 689 medical records (1988-1999) of women whose palpable cysts had been aspirated at the Breast Diagnostic Center, Women's and Children's Hospital, Los Angeles. These observations were correlated with the fluid cytologic reports. RESULTS: Except for frankly bloody fluid, all breast fluid cytologic reports listed the results as acellular, inadequate for cytologic diagnosis, or no malignant cells identified. CONCLUSION: In clinical practice only frankly bloody fluid should be submitted for cytologic analysis. All other cyst fluid should be discarded.

Preoperative paclitaxel and radiotherapy for locally advanced breast cancer: surgical aspects.

INTRODUCTION: Approximately 15% of breast cancer patients present with large tumors that involve the skin, the chest wall, or the regional lymph nodes. Multimodality therapy is required, to provide the best chance for long-term survival. We have developed a regimen of paclitaxel, with concomitant radiation, as a primary therapy in patients with locally advanced breast cancer. METHODS: Eligible patients had locally advanced breast cancer (stage IIB or III). After obtaining informed consent, patients received paclitaxel (30 mg/m2 during 1 hour) twice per week for 8 weeks and radiotherapy to 45 Gy (25 fractions, at 180 cGy/fraction, to the breast and regional nodes). Patients then underwent modified radical mastectomy followed by postoperative polychemotherapy. RESULTS: Twenty-nine patients were enrolled. Of these, 28 were assessable for clinical response and toxicity, and 27 were assessable for pathological response. Objective clinical response was achieved in 89%. At the time of surgery, 33% had no or minimal microscopic residual disease. Chemoradiation-related acute toxicity was limited; however, surgical complications occurred in 41% of patients. CONCLUSIONS: Preoperative paclitaxel with radiotherapy is well tolerated and provides significant pathological response, in up to 33% of patients with locally advanced breast cancer, but with a significant postoperative morbidity rate.

Follicular lesions of thyroid: a 5-year fine-needle aspiration experience.

BACKGROUND: Fine-needle aspiration (FNA) of the thyroid is of limited value in discriminating between nonneoplastic and neoplastic lesions in approximately 5-29% of patients. Indeterminate lesions are due primarily to the overlapping cytologic features found in follicular lesions. In this report, the authors describe their experience with FNA biopsy of the thyroid, concentrating on the analysis of those aspirates placed in the follicular lesion category. METHODS: A blinded, retrospective analysis of 92 patients who underwent FNA and were diagnosed with follicular lesions was performed by three of the authors (T.S.G., B.D.F., and M.O.) at a multihead microscope. A worksheet assessing a variety of cytologic and architectural features was filled out for each FNA patient. The reviewers then reached a consensus diagnosis. RESULTS: The reviewers agreed with the reported FNA diagnosis of follicular lesion in 63 of the 92 patients studied. No distinguishing cytologic features predictive of the histologic outcome were found in any of these 63 patients. Seven patients were judged by the reviewers to have insufficient cells for evaluation. In the remaining 22 patients, the reviewers' diagnoses were in agreement with the histologic diagnoses in 17 patients. CONCLUSIONS. The authors found that there is a gray area in the cytologic diagnosis of patients with thyroid lesions by FNA due to inherent similarities at the light microscopic level. However, increased specificity may be achieved by careful attention to cytologic features and morphologic detail. Skillful application of FNA techniques, with the recovery of an adequate sample, will further decrease both interpretive errors and the number of patients diagnosed with "follicular lesions."

Fine needle aspiration (FNA) biopsy of palpable breast masses: comparison of conventional smears with the Cyto-Tek MonoPrep system.

BACKGROUND: One of the limitations preventing the widespread use of fine-needle aspiration (FNA) is that it requires skill to obtain an adequate sample and well prepared smears. In this study, a new monolayer technique, the Cyto-Tek MonoPrep (MP) system, which obviates the need for smear preparation, was evaluated against conventional smear (CS) preparation for palpable breast lesions. METHODS: A total of 44 paired CS/MP breast FNA specimens were studied. The authors blindly analyzed the CS and the MP slides separately, then by a side-by-side evaluation. The two methods were compared with respect to diagnostic concordance, cellularity, cell preservation, background debris, and time needed to prepare and diagnose each case. RESULTS: An exact diagnostic correlation was present in 34 of 44 (77%) cases. The 10 noncorrelating cases were caused by decreased cellularity in the MP cases; nonetheless, 7 of these were correctly assigned to the right general diagnostic category, whereas the remaining 3 cases had insufficient cells. In addition to overall lesser cellularity on MP, fibroadenoma cases had smaller epithelial sheets and absence of stroma compared with CS. Both methods had comparable cellular preservation and diagnostic evaluation time, but background debris and preparation time were greater for MP. CONCLUSION: CS are favored over MP for the preparation of breast FNA specimens in centers with specialized FNA services because of their higher diagnostic yield, ease of preparation, and availability for immediate cytologic evaluation. However, in settings where specimens are collected sporadically by unskilled clinicians, the MP system may prove to be useful as an alternative or an adjunct to CS. Cancer (Cancer Cytopathol)

Linkage analysis and loss of heterozygosity for chromosome arm 1p in familial breast cancer.

We conducted linkage analysis of 64 multiple-case families with early-onset bilateral breast cancer using DNA markers on chromosome band 1p36. Evidence against tight linkage was obtained using a dominant model for transmission (summary LOD scores at recombination fraction theta = 0.000001 were -4.71 for D1S160 and -2.70 for D1S170). Similar results were obtained after excluding 20 families that were potentially attributable to BRCA1 or BRCA2. We also investigated loss of heterozygosity for a panel of markers on chromosome arm 1p using breast tumors from affected family members. The most common regions of allele loss were 1p36 (32% for D1S160, 35% for D1S243) and 1p32 (51% for MYCL). The frequency and location of 1p allele loss did not differ substantially from previous studies of sporadic breast cancer. We conclude that 1p36 probably does not contain a locus of susceptibility for a large proportion of breast cancer families, but a variety of loci on 1p may contribute to progression of familial and sporadic disease. Genes Chromosomes Cancer 25:354-361, 1999.

A breast clinic in a department of obstetrics and gynecology.

In 1988, the Department of Obstetrics and Gynecology of the University of Southern California School of Medicine; created its own Breast Diagnostic Center for training resident physicians and providing breast care for outpatients and inpatients of Women's and Children's Hospital, Los Angeles, California. The structure and function of the Breast Diagnostic Center allow residents to be directly involved in and responsible for evaluation and care of benign breast problems and allow comprehensive breast-care education and integration of referral breast services for residents and patients. Direct faculty supervision, uniform history and physical records on printed forms, fine-needle aspirations and breast biopsies, and staff assistance with follow-up and patient tracking maximize resident physician education and experience. This departmental approach to resident physician training in breast care can be adapted to the resources and logistics of any department of obstetrics and gynecology.

p53 and thymidylate synthase expression in untreated stage II colon cancer: associations with recurrence, survival, and site.

We initiated a retrospective study to determine whether p53 status and thymidylate synthase (TS) protein expression in primary colon tumors influence recurrence and survival for patients with stage II colon cancer. Tumor specimens from 45 consecutive untreated patients with stage II colon cancer were examined for p53 and TS protein expression using immunohistochemistry. The median follow-up was 5.1 years. Eighteen patients had left-sided tumors, and 27 had right-sided tumors. Fourteen of 45 patients (31%) developed recurrence. p53 overexpression was detected in the tumors of 18 patients (40%); 10 patients (55%) with p53 overexpression recurred; and 4 of 27 (15%) without evidence of p53 overexpression recurred (P = 0.002). High TS expression was detected in the tumors of 16 patients (36%): 8 patients (50%) with high TS expression recurred, and 6 patients (21%) with low TS expression recurred (P = 0.027). Patients with p53 overexpression had a significantly poorer survival than did those patients without p53 overexpression (P < 0.001). High TS expression was associated with poor survival (P = 0.004). p53 overexpression and high TS expression were significantly associated with left-sided tumors (P = 0.003 and P = 0.022). Thirteen of 16 patients (81%) with high TS expression also overexpressed p53, and 24 of 29 patients (81%) with low TS expression did not manifest p53 overexpression (P < 0.001). p53 and TS expression in primary stage II colon cancer are associated and appear to influence recurrence and survival. In this pilot study, left-sided tumors demonstrate significantly more p53 overexpression and significantly higher TS expression than do right-sided tumors, which may explain the significantly poorer survival for patients with left-sided tumors.

Original p53 status predicts for pathological response in locally advanced breast cancer patients treated preoperatively with continuous infusion 5-fluorouracil and radiation therapy.

PURPOSE/OBJECTIVE: 1) To test feasibility of preoperative continuous infusion (c.i.) 5-Fluorouracil (5-FU) and radiation (RT) in locally advanced breast cancer. 2) To study clinical and pathological response rates of 5-FU and radiation. 3) To attempt preliminary correlations between biological probes and pathological response. METHODS AND MATERIALS: Previously untreated, locally advanced breast cancer patients were eligible: only patients who presented with T3/T4 tumors that could not be resected with primary wound closure were eligible, while inflammatory breast cancer patients were excluded. The protocol consisted of preoperative c.i. infusion 5-FU, 200 mg/m2/day with radiotherapy, 50 Gy at 2 Gy fractions to the breast and regional nodes. At mastectomy, pathological findings were classified based on persistence of invasive cancer: pathological complete response (pCR) = no residual invasive cells in the breast and axillary contents; pathological partial response (pPR) = presence of microscopic foci of invasive cells in either the breast or nodal specimens; no pathological response (pNR) = pathological persistence of tumor. For each patient pretreatment breast cancer biopsies were analyzed by immunohistochemistry for nuclear grade, ER/PR hormonal receptors, her2/neu and p53 overexpression. RESULTS: Thirty-five women have completed the protocol and are available for analysis. 5-FU was interrupted during radiation in 10 of 35 patients because of oral mucositis in 8 patients, cellulitis in 1, and patient choice in another. Objective clinical response rate before mastectomy was 71% (25 of 35 patients): 4 CR, 21 PR. However, in all 35 patients tumor response was sufficient to make them resectable with primary wound closure. Accordingly, all patients underwent modified radical mastectomy: primary wound closure was achieved in all patients. At mastectomy there were 7 pCR (20%), 5 pPR (14%) and the remaining 23 patients (66%) had pathological persistence of cancer (pNR). Variables analyzed as potential predictors for pathological response (pPR and pCR) were: initial TNM clinical stage, clinical response, nuclear grade, hormonal receptor status, p53 overexpression, and Her2/neu overexpression in the pretreatment tumor biopsy. Only initial p53 status (lack of overexpression at immunohistochemistry) significantly correlated with achievement of a pathological response to this regimen (p = 0.010). CONCLUSION: The combination of c.i. 5-FU and radiation was well tolerated and generated objective clinical responses in 71% of the patients. With the limitation of the small sample size, the complete pathological response achieved (20%) compares favorably with that reported in other series of neoadjuvant therapy for similar stage breast cancer. These preliminary data suggest that initial p53 status predicts for pathological response (pPR and pCR) to the combination of c.i. 5-FU and radiotherapy in locally advanced breast cancer.

Preoperative 5-fluorouracil and radiation therapy for locally advanced breast cancer.

BACKGROUND: Fifteen percent of breast cancer patients present with large tumors involving skin or chest wall. Often, surgery with primary wound closure is impossible. We used neoadjuvant chemoradiation in locally advanced breast cancer patients, in hopes of increasing resectability. METHODS: Eligible patients had locally advanced breast cancer deemed unresectable with primary wound closure. Patients received 8 weeks of infusional 5-fluorouracil (5-FU) 200 mg/m2 per day and radiation therapy to 50 Gy. Patients rendered resectable underwent modified radical mastectomy (MRM) followed up by chemotherapy. RESULTS: Of 30 evaluable patients, 73% had an objective clinical response. All were able to undergo MRM with primary wound closure; 63% had residual disease, 20% had minimal microscopic disease, and 17% had complete pathologic response. Treatment-related toxicity was minimal. Surgical morbidity was not increased. CONCLUSIONS: Infusional 5-FU with concomitant radiotherapy is well tolerated and effective at producing shrinkage in the majority of patients, converting inoperable breast cancer to easily resectable disease.

Mucor pyelonephritis. Report of a case diagnosed by urine cytology, with diagnostic considerations in the workup of funguria.

BACKGROUND: Isolated renal mucormycosis is an uncommon kidney infection affecting patients with underlying systemic diseases and intravenous (IV) drug abuse. We report a unique case in the cytologic literature in which urine cytology provided insight into the diagnosis, renal mucormycosis. CASE: The patient, a diabetic and IV drug abuser, presented with complaints of left flank pain, fever and dysuria. All urine cultures were negative. A computed tomography (CT) scan showed changes consistent with left acute pyelonephritis, and the patient was treated for a presumed diagnosis of bacterial pyelonephritis. Late in the hospital stay, the cytology laboratory diagnosed Mucor in a single urine specimen, but the patient had already been discharged. The patient was never treated for funguria, only to present again with left flank pain 13 months later. An abdominopelvic CT scan showed progression to left chronic pyelonephritis. The patient, however, left the hospital against medical advice before any further workup could be completed. CONCLUSION: Renal mucormycosis should be considered part of the differential diagnosis in patients with underlying diseases or IV drug abuse who present with symptoms of acute pyelonephritis. The differential diagnosis of Mucor funguria should also include fungal ball in the renal pelvis or urinary bladder and fungal cystitis.

Core needle biopsy. A useful adjunct to fine-needle aspiration in select patients with palpable breast lesions.

BACKGROUND: Fine-needle aspiration (FNA) biopsy is an established, highly accurate method for diagnosing palpable breast lesions. However, in some cases a definitive diagnosis cannot be made by FNA alone, either due to the inherent limitations of cytology itself or the ability to obtain adequate material for diagnosis. This study evaluated the usefulness of a supplemental core needle biopsy performed by a cytopathologist in conjunction with an FNA biopsy in select patients. METHODS: Twelve patients with palpable breast lesions underwent the combined FNA/core needle biopsy procedure during the study period from March 1995 through March 1996. All 12 patients first had an FNA aspiration that was preliminarily evaluated by the FNA cytopathologist while the patient was at the clinic. If the cytopathologist was unable to render a definitive diagnosis of the lesion type or if a repeat FNA was requested by the clinician because of a previous non-definitive FNA result, a core needle biopsy was then performed. RESULTS: When the FNA and the core needle biopsies were reviewed together, a correct definitive diagnosis was made in 10 of the 12 cases. In contrast, review of the FNA material alone yielded a correct definitive diagnosis in only five cases. CONCLUSIONS: The supplemental core needle biopsy was found to be especially useful in: 1) providing a definitive diagnosis of infiltrating carcinoma in those cases in which the FNA diagnosis was reported as "suspicious;" 2) providing ample tissue for ancillary studies; and 3) differentiating a phyllodes tumor from a fibroadenoma. It is the authors' opinion that the FNA cytopathologist is the physician best qualified to perform the combined FNA/core needle biopsy procedure should he/she deem it necessary.

Detection of hyperdiploid malignant cells in body cavity effusions by fluoresence in situ hybridization on ThinPrep slides.

BACKGROUND: Benign body cavity effusions sometimes cannot be distinguished from malignant ones by conventional cytology. The authors performed fluorescence in situ hybridization (FISH) on ThinPrep slides using chromosome specific probes to see if hyperdiploid malignant cells could be detected in 20 body cavity effusions. The results were then compared with those of conventional cytology. METHODS: A total of 20 body cavity effusions from 19 patients were studied using conventional cytology and FISH. Probes specific for chromosomes 3, 8, 10, and 12 were used to detect hyperdiploidy on ThinPrep slides (Cytyc Corporation, Boxborough, MA). RESULTS: A total of 13 patients had malignant conditions (either prior history of malignancy or the presence of malignancy anywhere in the body). Conventional cytology and FISH were both positive in 5 of these patients (6 samples) and negative in 2 patients. The results for one sample were inconclusive by both methods. There were 5 discrepant cytology-FISH results in patients with malignant conditions. One sample was positive by FISH and negative by cytology, one was positive by FISH and "atypical" by cytology, and three were inconclusive by FISH and negative by cytology. FISH results were either negative (in 4 samples) or inconclusive (in 2 samples) in the 6 patients with benign conditions. CONCLUSIONS: FISH can detect hyperdiploid malignant cells in body cavity effusions and is especially useful when the major cell population consists of malignant cells that cannot be differentiated from mesothelial or "atypical" cells. It is less useful in detecting a small population of malignant cells hidden in an inflammatory or reactive cell background. More studies are needed to establish diagnostic criteria further and to assess the clinical usefulness of this procedure.

Local anesthesia for fine-needle aspiration biopsy of palpable breast masses: the effectiveness of a jet injection system.

To determine the effectiveness of the Biojector 2000 needle-free lidocaine injection system in achieving satisfactory local anesthesia for fine-needle aspiration (FNA) of palpable breast lesions, we studied 29 female patients. Each patient served as her own control and had two FNA biopsies performed on the lesion. The first FNA biopsy was preceded by either no anesthesia, ethyl chloride cold spray, or traditional needle lidocaine injection. The second FNA was preceded by the Biojector 2000. Twenty-four patients (83%) reported that they preferred the Biojector 2000 over either no anesthesia, ethyl chloride spray, or needle and syringe lidocaine injection. The Biojector 2000 needle-free injection system is an effective and useful method of local anesthesia for FNA of palpable breast masses.

Xanthogranulomatous cystitis as a cause of elevated carcinoembryonic antigen mimicking recurrent colorectal cancer. Report of a case.

We report a case of xanthogranulomatous cystitis that developed in a patient with a history of colon cancer. While undergoing adjuvant chemotherapy with fluorouracil and levamisole, rising carcinoembryonic antigen (CEA) levels and the appearance of a pelvic mass, suspicious for recurrent cancer, were identified. Exploratory laparotomy demonstrated the presence of a benign condition of the bladder, xanthogranulomatous cystitis, which was resected by partial cystectomy. CEA levels have normalized. This is the first reported case of xanthogranulomatous cystitis producing an elevated CEA level.

Bone marrow examination for the diagnosis of mycobacterial and fungal infections in the acquired immunodeficiency syndrome.

In a series of 342 bone marrow examinations from 314 patients with human immunodeficiency virus infection, 70 examinations (20%) detected opportunistic mycobacterial or fungal infections. One hundred eleven of the 314 patients had such infections, and, hence, 63% (70/111) were detected by bone marrow examination. Special stains for microorganisms detected 16 (32%) of 50 Mycobacterium avium complex infections, 10 (22%) of 45 Mycobacterium tuberculosis infections, eight (73%) of 11 Histoplasma capsulatum infections, and five (83%) of six Cryptococcus neoformans infections. Bone marrow cultures detected 36 (72%) of the 50 M avium complex infections, 13 (29%) of the 45 M tuberculosis infections, and 63% of the fungal infections. Marrow examination revealed infection in only one of the 70 specimens (1%) collected to evaluate thrombocytopenia alone or hematologic malignancy, but in 69 (25%) of 274 with fever, neutropenia, anemia, or miscellaneous other indications for marrow examination. Granulomas were detected in 102 (30%) of the biopsy specimens, including 71 (64%) of those in cases with mycobacterial or fungal infection. The granulomas showed caseous necrosis in nine cases, all in patients with tuberculosis, and the 27 cases with tuberculosis-associated granulomas tended to show large, tightly cohesive granulomas. The presence of granulomas correlated with opportunistic infection in 82 (80%) of 102 cases. Without granulomas, special stains were positive in only eight (3%) of 240 specimens. These results suggest that (1) bone marrow granulomas are a common and valuable histologic clue to opportunistic infection; (2) without them, special stains may not be a cost-efficient way to diagnose such infection; and (3) bone marrow examination can be a useful method of diagnosing opportunistic mycobacterial and fungal infections in patients with fever, anemia or neutropenia, and underlying human immunodeficiency virus infection.