Fine-needle aspiration diagnosis of metastatic urothelial carcinoma: a review.

Urothelial carcinoma (UC) is the most common malignant neoplasm of the urinary tract. Metastases of UC are most common in the regional lymph nodes, lungs, liver, bone, and adrenal glands. Fine-needle aspiration cytology diagnosis of such metastases can be difficult, particularly in the setting of incomplete clinical history or when multiple primary neoplasms may be present. This review focuses on the cytologic features helpful in differentiating UC from its potential mimics, as well as ancillary studies that may be helpful in the distinction.

Status of HER-2 in male and female breast carcinoma.

BACKGROUND: HER-2 overexpression is seen in 20% to 30% of invasive female breast carcinomas. Besides being prognostic, HER-2 may also be predictive of response to therapy. Similar studies in male breast carcinoma are lacking. We compared the overexpression and amplification of HER-2 in female and male breast carcinoma. DESIGN: Formalin-fixed, paraffin embedded archival material from 58 invasive male breast carcinomas and 202 invasive female breast carcinomas were immunostained for HER-2. Scoring was performed according to established guidelines. Each case was also assessed for HER-2 gene amplification by fluorescence in-situ hybridization (FISH) utilizing the PathVysion assay (Vysis corporation, Downers Grove, Illinois). RESULTS: There were 58 male patients who ranged in age from 38 to 92 years (mean 63). Thirty-five (60%) were T1 lesions and 23 (40%) were T2 lesions. Twenty-five patients (43%) had positive lymph nodes. One (1.7%) of the 58 cases showed 3+ staining of HER-2. The remaining 57 cases did not show overexpression. There was no amplification of the HER-2 gene in any of the cases. There were 202 female patients who ranged in age from 26 to 96 years (mean 52). In all, 129 (64%) were T1 lesions, 61 (30%) were T2 lesions, and 13 (6%) were T3 lesions. Fifty-two (26%) showed positive staining with HER-2 (44 cases 3+, 8 cases 2+). The remaining 150 (74%) did not show overexpression. There was amplification of HER-2 gene in 55 (27%) of the cases. Two of the cases negative by FISH were 3+ positive by IHC. CONCLUSIONS: HER-2 is overexpressed in approximately 27% of female breast carcinomas. A high level of correlation is demonstrated between IHC and FISH techniques. Gene amplification of HER-2 does not play a role in male breast carcinoma. The rate of single-copy overexpression of HER-2 appears identical in male and female breast carcinoma.

The effect of glucagon-like peptide 2 on intestinal permeability and bacterial translocation in acute necrotizing pancreatitis.

BACKGROUND: Acute pancreatitis (AP) initiates a generalized inflammatory response that increases intestinal permeability and promotes bacterial translocation (BT). Impairment of the intestinal epithelial barrier is known to promote BT. Glucagon-like peptide 2 (GLP-2), a 33 residue peptide hormone, is a key regulator of the intestinal mucosa by stimulating epithelial growth. The purpose of this study was to determine whether GLP-2 decreases intestinal permeability and BT in AP. METHODS: To examine whether GLP-2 can decrease intestinal permeability and thereby decrease BT in acute necrotizing pancreatitis, 34 male Sprague-Dawley rats (200 to 300 g) were studied. AP was induced in group I and group II by pressure injection of 3% taurocholate and trypsin into the common biliopancreatic duct (1 mg/kg of body weight). The potent analog to GLP-2 called ALX-0600 was utilized. Group I rats received GLP-2 analog (0.1 mg/kg, SQ, BID) and group II rats received a similar volume of normal saline as a placebo postoperatively for 3 days. Group III and group IV received GLP-2 analog and placebo, respectively. At 72 hours postoperatively, blood was drawn for culture of gram-negative organisms. Specimens from mesenteric lymph nodes (MLN), pancreas and peritoneum were harvested for culture of gram-negative bacteria. Intestinal resistance as defined by Ohm's law was determined using a modified Ussing chamber to measure transepithelial current at a fixed voltage. A point scoring system for five histologic features that include intestinal edema, inflammatory cellular infiltration, fat necrosis, parenchymal necrosis, and hemorrhage was used to evaluate the severity of pancreatitis. Specimens from MLN, pancreas, jejunum, and ileum were taken for pathology. RESULTS: All group I and group II rats had AP. The average transepithelial resistance in group I was 82.8 Omega/cm(2) compared with 55.9 Omega/cm(2) in group II (P <0.01). Gram-negative BT to MLN, pancreas, and peritoneum was 80%, 0%, and 0%, respectively in group I compared with 100%, 30%, and 20% translocation in group II. CONCLUSION: GLP-2 treatment significantly decreases intestinal permeability in acute pancreatitis.

Fine-needle aspiration of extranodal and extramedullary hematopoietic malignancies.

There is relatively little information concerning the use of fine-needle aspiration (FNA) to diagnose extranodal and extramedullary hematopoietic malignancies. Seventy-one such cases diagnosed by FNA form the basis of this study. Seventy-one cases of FNAs performed between 1988 and 1998 on extranodal and extramedullary hematopoietic malignancies were reviewed in order to evaluate the usefulness of this technique in diagnosing these entities as well as to assess patterns of relapse. There were 45 male and 26 female patients ranging in age from 29-86 years (mean, 68 years). Sixty-six patients had a previous history of a hematopoietic malignancy. Aspirates from 65 of these patients were consistent with the patient's known primary. One aspirate of a paravertebral mass from a multiple myeloma patient showed extramedullary hematopoiesis. The remaining five aspirates were cases of multiple myeloma that first presented as soft tissue masses. The most common malignancies were lymphoma: 52 cases (73%), 48 large cell lymphomas, four mixed small and large cell lymphoma; followed by multiple myeloma: 12 cases (17%); leukemia: four cases (5.4%); Hodgkin disease: two cases (2.8%); and one case of extramedullary hematopoiesis. The aspirate sites were soft tissue: 23 cases (32%); bone: 17 cases (24%); kidney: 14 cases (20%); liver: 11 cases (15%); lung: three cases (4%); adrenal: two cases (3%); and eye: one case. The interval between primary diagnosis and FNA was 1-36 months (mean, 13 months). In conclusion, 98% of the aspirates were neoplastic in patients with a known history of hematopoietic malignancies. The most common site of involvement was soft tissue in 23 (32%) cases. In five patients with multiple myeloma, the FNA diagnosis prompted a work-up to find the primary site of involvement. FNA is a useful technique in assessing extranodal and extramedullary hematopoietic malignancies.

Fine-needle aspiration biopsy of the liver: a multicenter study of 602 radiologically guided FNA.

With improved radiologic techniques fine-needle aspiration (FNA) is becoming a rapid, effective diagnostic method in evaluating a wide range of liver masses. Review of six hundred two radiologically guided liver aspirates performed over a ten-year period forms the basis of this report.

Carcinosarcoma of the renal pelvis.

Carcinosarcoma of the renal pelvis is a rare neoplasm, with 7 cases reported. This lesion should be differentiated from a sarcomatoid variant of renal cell carcinoma; it is usually associated with a poor prognosis. We report an additional case of renal pelvic carcinosarcoma.

Fine-needle aspiration of scalp lesions.

A variety of inflammatory and neoplastic scalp lesions are encountered in surgical pathology. However, the literature on fine-needle aspirations (FNAs) of the scalp is exceedingly rare. We report on a series of 70 FNAs involving cutaneous and subcutaneous lesions on the scalp. A total of 70 fine-needle aspirations of cutaneous and subcutaneous scalp lesions was reviewed to identify patterns of metastasis to the scalp and to demonstrate the effectiveness of FNA in diagnosing these lesions. There were 42 male and 28 female patients, ranging in age from 29-91 yr (mean, approximately 61 yr). Sixty-one patients had a previous history of malignancy. Of these aspirates, 59 were neoplastic, consistent with the patient's known primary. One case was an abscess, and the remaining case was unsatisfactorvy for cytologic evaluation. Follow-up biopsy revealed granulomatous inflammation. The most common primary tumor to metastasize to the scalp was lung carcinoma, which was seen in 18 cases, followed by hematopoietic malignancies in 14 cases. Melanoma was identified in 6 cases, head and neck tumors in 5 cases, renal malignancies in 4 cases, gastrointestinal tumors in 3 cases, sarcoma in 3 cases, breast and prostate malignancy in 2 cases each, and an olfactory neuroblastoma and meningioma in 1 case each. The remaining 9 aspirates were from patients who did not have a previous history of malignancy. These included 6 benign aspirates consisting of 3 epidermal inclusion cysts, 2 lipomas, and 1 neurofibroma. Two aspirates were malignant and included 1 primary squamous-cell carcinoma and 1 metastatic adenocarcinoma of unknown origin. The remaining case was unsatisfactory for cytologic evaluation. Follow-up biopsy of this lesion showed noncaseating granulomas. Of the aspirates from patients with a previous history of malignancy, 97% were neoplastic. Lung carcinoma and hematopoietic malignancies were the most common neoplasms that metastasized to the scalp. Since the scalp is a common site for metastasis, awareness of this fact is useful to both oncologists and dermatologists. It must be understood that FNA can provide a rapid and accurate diagnosis in the evaluation of scalp masses.

The effect of interleukin-6 on bacterial translocation in acute canine pancreatitis.

BACKGROUND: Bacterial translocation from the gut to mesenteric lymph nodes and other extraintestinal sites is an important source of infection in acute pancreatitis. Impaired host immunity is known to promote bacterial translocation. Interleukin-6 (IL-6) is a multifunctional cytokine that regulates the immune response, acute phase reaction, and hematopoiesis. METHODS: Twenty-four mongrel dogs (18-29 kg) were studied in four equal groups. In Groups I and II, acute pancreatitis was induced by direct pressure injection of 4% taurocholate and trypsin into the pancreatic duct at laparotomy. Groups III and IV had only laparotomy. Group I and III dogs were given IL-6 (50 microg/kg/d, sq) daily starting 24 h after operation and Group II and IV dogs received an equal volume of saline administered at similar time. All animals had blood drawn for culture, complete blood count (CBC), platelets, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and amylase on d 0, 1, 4, and 7. On d 7, mesenteric lymph nodes (MLN), spleen, liver, pancreas, and cecum were harvested for pathology study and for cultures of aerobic and anaerobic bacteria. Quantitative cecal cultures of aerobic and anaerobic bacteria were obtained. RESULTS: All Group I and Group II dogs had severe pancreatitis. The increase of plasma CRP in Group I was sustained throughout treatment (1.3+/-0.3 on d 0 vs 3.1+/-0.3*, 3.0+/-0.3*, and 2.9+/-0.3* on d 1,4, and 7, respectively). Plasma CRP was increased in Group II on d 1 and d 4 (1.3+/-0.3 mg/dL on d 0 vs 3.6+/-0.3* mg/dL on d 1, and 3.1+/-0.3* on d 4, *p < 0.05). There were no differences in white blood cell (WBC) count, differential, platelets, and ESR between Groups I and II. Bacterial translocation to MLN was lower in Group I (1/6) than in Group II (6/6) (p < 0.05). All 6 dogs in Group II had bacterial spread to distant sites compared to 2 of 6 dogs in Group I (p = 0.066). Both MLN and other distant organ cultures were negative in Group III and only 1 of 6 MLN cultures was positive in Group IV. CONCLUSIONS: IL-6 treatment decreases bacterial translocation to MLN and may be beneficial in reducing septic complications in acute pancreatitis.

Role of fine-needle aspiration in the clinical management of solid organ transplant recipients: a review.

BACKGROUND: We evaluated the clinical course of the solid-organ transplant population at our institutions to determine the role of fine-needle aspiration (FNA) in the clinical management of this subgroup of patients. METHODS: 1196 allograft recipients (522 liver, 288 cardiac, 250 renal, 131 lung, 5 heart and lung) were reviewed. A total of 62 (5.2%) (32 liver, 23 heart, 6 lung, and 1 renal) transplant patients underwent an FNA procedure. Thirty-seven males and 25 females were included, ranging in age from 18 to 71 years (mean 50 years). RESULTS: Of the 62 fine-needle aspirates, 29 (47%) were neoplastic. The most common malignancies aspirated were malignant solid tumors (15 cases)-including 8 epithelial malignancies, 5 hepatocellular carcinomas, and 2 mesenchymal neoplasms-followed by posttransplant lymphoproliferative disorders (14 cases). Thirteen (21%) aspirates were inflammatory. The remaining 20 (32%) cases were benign aspirates from various sites (9 liver, 3 breast, 2 thyroid, 2 soft tissue, 2 lung, and 2 vertebral body). Surgical and/or autopsy material was available in 34 cases (55%). There was agreement between the tissue diagnosis and FNA material in 33 cases (97%). One case (3%) was a false negative. No false-positive cases were recorded. CONCLUSIONS: This study showed that over 50% of the aspirates were benign, justifying a conservative approach in the clinical management of these patients. Histologic correlation was available in 54% of the cases with an overall specificity of 100% and a sensitivity of 97%. We conclude that FNA is a highly sensitive and specific technique in the evaluation of lesions occurring in posttransplant patients. Cancer (Cancer Cytopathol)

The effect of lexipafant on bacterial translocation in acute necrotizing pancreatitis in rats.

Bacterial translocation (BT) from the gastrointestinal tract to mesenteric lymph nodes (MLNs) and other extra intestinal organs is an important source of infection in acute pancreatitis (AP). Lexipafant (BB-882) is a potent platelet-activating factor receptor antagonist that has an anti-inflammatory effect. To examine whether BB-882 could affect BT in acute necrotizing pancreatitis, 48 male Sprague Dawley rats (250-350 g) were studied. AP was induced in Group I and Group II by pressure injection of 3% taurocholate and trypsin into the common biliopancreatic duct (1 mL/kg of body weight). Group I rats received BB-882 (10 mg/kg, i.p. qd) and Group II rats received a similar volume of normal saline as a placebo postoperatively for 2 days. Group III and Group IV received BB-882 and placebo, respectively, after an exploratory laparotomy. At 48 hours postoperatively, blood was drawn for culture, serum amylase, and tumor necrosis factor (TNF)-alpha determinations. Specimens from MLNs, spleen, liver, pancreas, and cecum were harvested for culture of gram-positive, gram-negative, and anaerobic bacteria. Quantitative cecal cultures of gram-positive, gram-negative, and anaerobic bacteria were obtained. A point scoring system for five histological features that include interstitial edema, inflammatory cellular infiltration, fat necrosis, parenchymal necrosis, and hemorrhage was used to evaluate the severity of pancreatitis. There was no difference in serum amylase levels (2415 +/- 127 IU/L versus 2476 +/- 170 IU/L), serum TNF-alpha levels (7820 +/- 1396 pg/mL versus 7318 +/- 681 pg/mL), and the mean pancreatic histology score (5.9 +/- 1.2 versus 6.5 +/- 1.1) between Group I and Group II, respectively (P > 0.05). Seven of 12 Group I rats had BT to MLNs, compared with 11 of 12 rats in Group II (P > 0.05). Five of 12 Group I rats had BT to distant sites such as pancreas, spleen, liver, and/or blood, compared with 11 of 12 rats in Group II (P < 0.05). BB-882 treatment decreases bacterial spread to distant sites, but does not reduce serum amylase levels and serum TNF-alpha levels or ameliorate pancreatic damage in rats with AP.

Utilization of fine-needle aspiration in the diagnosis of metastatic tumors to the kidney.

Renal masses secondary to metastases are not common. Few comprehensive reviews exist, which consist primarily of autopsy and radiologic reports. The purpose of this study was to review the types and incidences of various neoplasms which metastasize to the kidney and to determine the usefulness of fine-needle aspiration (FNA) in diagnosing them. Two hundred and sixty-one radiologically guided FNAs of renal lesions over a 9-yr period were reviewed. The diagnoses of the 261 renal FNAs were as follows: 136 (52%) were malignant, 111 (43%) were benign, and 14 (5%) were unsatisfactory. Of the 136 positive FNAs, 28 (21%) revealed metastatic tumors. The overall incidence of renal FNAs displaying metastatic tumors was 11%. Among the 28 patients with metastases to the kidney, 23 patients were men and 5 were women, with the mean age being 58 yr. Twenty-five patients (89%) had prior history of a primary malignancy, including lung carcinoma (11 cases, 39%), lymphoma (8 cases, 29%), hepatocellular carcinoma (3 cases, 11%), and one case each of breast, pancreatic, and cervical cancer. In the remaining 3 patients (11%), with metastatic adenocarcinoma (2 cases) and squamous-cell carcinoma (1 case), the primary tumor site remained unknown despite an extensive clinical workup. Overall survival after FNA was poor, with a mean of 9.8 mo. FNA is useful in the diagnosis of masses in the kidney secondary to metastatic disease. This information is of clinical importance, principally in the exclusion of a primary malignancy, but also to avoid unnecessary surgery and to plan for subsequent patient care.

Low-stage carcinoma of the male breast. A histologic, immunohistochemical, and flow cytometric comparison with localized female breast carcinoma.

Male breast carcinoma (MBC) accounts for only 1% of total mammary carcinomas. Controversy exists about whether MBC differs clinically and pathologically from female breast carcinoma (FBC). We compared 10 archival cases with 75 stage-matched FBCs. Clinical data, histologic details, immunostains for mammary lineage markers, and results of several putative "prognostic" analyses were addressed, including DNA ploidy and expression of c-erbB-2 (neu) oncoprotein and p53 protein. Cumulative literature data on 2,530 MBCs were contrasted with information from 135 institutional cases of FBC. A statistically significant difference in grade 3 lesions at low stage persisted when MBCs of all stages were compared with similar FBCs. For stages I and IIA, 5-year survival was 60% and 86% for MBCs and FBCs, respectively (also statistically significant). This difference disappeared when all stages were compared. A similar number of MBCs and FBCs, regardless of stage, demonstrated DNA aneuploidy with or without synthesis of S-100 protein, gross cystic disease fluid protein-15, c-erbB-2 protein, and p53 protein. Hormone receptor positivity was more common in MBC than in FBC at high tumor stages. Low-stage MBC and FBC differ biologically; MBCs tend to manifest at a higher grade with lessened 5-year survival. However, aside from distinctions in hormone receptor proteins, broader comparison of MBC and FBC at stages IIB and higher shows no significant differences in 5-year survival or expression of breast cancer-associated gene products.

Pancreatic masses: a multi-institutional study of 364 fine-needle aspiration biopsies with histopathologic correlation.

Only 15% of primary malignant tumors are confined to the gland at the time of presentation. Fine-needle aspiration (FNA) is valuable in confirming the malignant nature of these unresectable lesions. Benign pancreatic lesions and metastatic neoplasms can also be evaluated by fine-needle aspiration. We undertook a retrospective study to evaluate the efficacy of FNA in assessing pancreatic masses. Three hundred and sixty-four radiologically guided FNAs of the pancreas performed between 1986-1996 were reviewed. Surgical material was also evaluated when available and compared to the FNA material. There were 223 men and 141 women. Their ages ranged from 23-90, with a mean of 64 yr. Two hundred and twelve patients (58%) had primary malignant tumors, 183 had adenocarcinomas, 15 had mucinous cystadenocarcinomas, 12 had neuroendocrine tumors, and 2 had pleomorphic giant-cell carcinomas. Ninety-one (43%) had available surgical material which showed adenocarcinoma. Ninety-one patients (25%) had benign aspirates, including 53 showing benign ductal epithelium, 23 showing pancreatitis/inflammation. 10 showing pseudocysts, and 7 showing serous cystadenomas. Surgical material was available in 24 (26%) of these patients. Two of these showed adenocarcinoma. Sixteen aspirates (4%) were suspicious for malignancy, 13 (81%) of which showed adenocarcinoma on follow-up biopsies. Twenty-two aspirates (6%) showed metastatic neoplasms. Twenty-three (6%) had unsatisfactory specimens. Ten (43%) of these had follow-up biopsies, 3 of which were malignant. FNA of primary benign and malignant pancreatic masses is highly sensitive (98%) and specific (100%). Eighty-one percent of the suspicious lesions showed adenocarcinoma on follow-up biopsy. FNA of metastatic neoplasms to the pancreas is also very accurate. This technique can be useful in avoiding unnecessary surgery.

Malignant cutaneous and subcutaneous abdominal wall lesions: a fine-needle aspiration study.

Cutaneous and subcutaneous masses of the abdominal wall are uncommon. However, a variety of benign and neoplastic entities can be encountered in this region. We report a series of 22 fine-needle aspirations (FNA) of malignant cutaneous and subcutaneous lesions involving the abdominal wall. All of these lesions were metastatic neoplasms. There were 14 females and eight males, with an age range of 35-83 years (mean 65 years). Twenty-one had a previous history of malignancy. The mean interval between the primary diagnosis and FNA was 26 months (range 1.5-128 months). The sites of origin in order of decreasing frequency were colon (n = 4), ovary (n = 4), breast (n = 3), endometrium (n = 2), melanoma (n = 2), and one case each of cervix, urinary bladder, kidney, pancreas, gallbladder, and lymphoma. One case was a squamous-cell carcinoma of unknown origin. Fourteen of the 22 patients were dead at the end of this study, with a mean survival of 8.4 months (range 0.5-44 months) following FNA. One patient was alive with disease at 13 months, and seven patients were lost to follow-up. Based on this data and on review of the literature we conclude that the majority of malignant cutaneous and subcutaneous lesions of the abdominal wall subject to FNA biopsy are metastatic tumors which originate from intra-abdominal, pelvic, and retroperitoneal organs and that FNA is a highly useful technique in the assessment of these lesions of the abdominal wall.

Utilization of core wash material in the diagnosis of breast lesions by stereotactic needle biopsy.

BACKGROUND: Several reports have compared the results of fine-needle aspiration and stereotactic core needle biopsy in nonpalpable breast lesions. In this study the authors describe a simple method to retrieve cytologic material from a core breast biopsy sample that provides the diagnosis within 1 hour of the procedure. METHODS: Two hundred and eleven nonpalpable breast lesions were biopsied. Each core needle biopsy sample was placed in a mesh bag, and the bag and needle notch were washed in Cytolyt solution to obtain a monolayer using a commercial ThinPrep processor. The cytologic diagnoses were divided into four categories: benign, suspicious, malignant, and unsatisfactory, which then were compared with core needle biopsy results. RESULTS: Cytology reports of 211 lesions were as follows: 169 lesions (80%) were benign, 16 lesions (7.6%) were suspicious, 11 lesions (5.2%) were malignant, and 15 lesions (7.1%) were unsatisfactory. Core needle biopsy showed 165 of 169 samples (98%) to be benign and 4 to be malignant. Of the 16 suspicious smears, 10 were invasive carcinoma, 2 were in situ lesions, 3 were hyperplasias, and 1 was fibrosis. Of the 11 malignant smears, 10 were confirmed on core needle biopsy and 1 was read as atypia on the first core needle biopsy sample and malignant on a second, separate, follow-up core needle biopsy. Of the 15 unsatisfactory samples, 14 were found to be benign and 1 was found to be malignant on a separate, follow-up core needle biopsy. CONCLUSIONS: The core wash technique was 85% sensitive and 98% specific for malignancy. Only 7% of specimens were insufficient for diagnosis, and 93% of these were proven to be benign. This technique is useful for immediate (within 1 hour) diagnosis of breast lesions, alleviating patient anxiety and supplementing the diagnostic yield of the core biopsy.