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PubMed1986

Intraoperative autotransfusion in urologic oncology.

The value of autotransfusion is widely recognized in the surgical community and may be of increasing importance in prevention of acquired immunodeficiency syndrome and hepatitis. The concern of potential contamination of the blood with viable tumor cells has resulted in limited use of autotransfusion in cancer surgery. The objective of this study was to examine the benefits and safety of autotransfusion in patients undergoing major surgery of genitourinary tumors. Autotransfusion was used in 49 consecutive patients. Twenty-four patients had radical cystectomy, ten had radical prostatectomy, 13 had radical nephrectomy, and two had other types of operations. An autotransfusion machine (Haemonetics Cell Saver) was used. The follow-up included physical examination, chest roentgenogram every three months, and bone scan and computed tomographic scan if clinically indicated. Liver and renal profiles were routinely performed every three months. Five of 49 patients developed metastases during follow-up examination from 12 to 23 months. The low incidence of metastatic spread and the pattern of spread fall to implicate autotransfusion as a cause of tumor dissemination. Autotransfusion and predeposited blood banking may result in elimination of or significant reduction in homologous transfusions.

Adult↗
PubMed2001

Melanoma of the clavicular region: multimodal treatment.

HYPOTHESIS: Treatment for melanoma that has metastasized to the supraclavicular nodes should be intensive and use a multimodality approach. DESIGN: Retrospective analysis of clinical records. SETTING: Six primary care centers, 2 of which were referral centers. PATIENTS: Eighteen patients diagnosed as having a rare pattern of advanced melanoma metastatic to the clavicular region. INTERVENTION: Combined radiotherapy, chemotherapy, and thorough surgical excision of the affected nodal basins. MAIN OUTCOME MEASURE: Length of survival from time of diagnosis and treatment to time of follow-up. RESULTS: Median survival among the 18 patients was 28 months with a 22% survival rate at 5 years after diagnosis. Among patients who received radiotherapy to the clavicular node basin, mean length of survival was 88.7 months with a 50% 5-year survival rate compared with a mean length of survival of 33.8 months and an 8.3% 5-year survival rate in patients who did not receive radiotherapy (P<.001). Mean survival among patients who had supraclavicular node dissection was 45.8 months with a 23.1% survival rate at 5 years after diagnosis, compared with a mean survival of 52 months and a 20% 5-year survival rate among patients who did not receive therapeutic lymphadenectomy. Of the 11 patients who had therapeutic lymphadenectomy, 2 also received radiotherapy to the supraclavicular nodal basin and continued to be disease-free at 82 and 130 months. All long-term survivors had been treated with intra-arterial chemotherapy. CONCLUSION: In a series of patients with malignant melanoma metastatic to the clavicular lymph nodes, multimodality treatment using radiotherapy, chemotherapy, and thorough surgical excision of affected nodal basins provided an appreciable 5-year survival rate.

Adult↗
PubMed1986

The use of antikeratin antibodies in the immunohistochemical distinction between neuroendocrine (Merkel cell) carcinoma of the skin, lymphoma, and oat cell carcinoma.

Paraffin sections of formalin-fixed tumor samples from 26 patients with neuroendocrine (Merkel cell) carcinoma of the skin (NECS) were studied immunohistochemically with three monoclonal antibodies to low molecular weight keratin (MAB-K) and with antibodies to leukocyte common antigen (LCA), neurofilament (NF), neuron-specific enolase (NSE), S100 protein (S100), and chromogranin (CGN), to investigate the relative diagnostic value of these antibodies. Samples from 20 lymphomas, 10 non-oat cell undifferentiated carcinomas, 10 oat cell carcinomas, and 10 melanomas served as controls. Keratin was found in 25 of the 26 NECS and in all undifferentiated and oat cell carcinomas. A ball-like immunostaining for keratins, resembling an inclusion body was seen only in cases of NECS and some carcinoids. Neurofilament, NSE, and CGN were expressed by fewer NECS than was keratin and all NECS were negative for LCA and S100. None of the lymphomas and melanomas contained detectable keratin, NF, NSE, or CGN. Only the lymphomas stained with LCA. Only the melanomas were S100-positive. It is concluded that keratin is the most useful single discriminating marker in the separation of neuroendocrine (Merkel cell) carcinoma of the skin from lymphoma, melanoma and, when the characteristic inclusion-like pattern is seen, from metastatic oat cell carcinoma.

Adult↗
PubMed1985

Glycoconjugates of murine tumor lines with different metastatic capacities. II. Diversity of glycolipid composition.

A syngeneic tumor system in DBA/2 mice consisting of a methyl-cholanthrene-induced, weakly metastatic lymphoma, L5178YE (= Eb), its spontaneous strongly metastatic variant, L5178YES (= ESb), and an unrelated, methylcholanthrene-induced, metastasizing tumor, MDAY-D2, were used to study the relationship between metastatic behavior and composition of GSLs. The D-1-14C galactose and D-1-14C glucosamine-labelled neutral GSL and gangliosides of these tumor cells, and additionally ConA-stimulated spleen T cells from normal mice, were analysed by thin-layer chromatography. Unlabelled GSLs of the tumors were also characterized by (HPLC) after perbenzoylation. Results obtained with the radioactively labelled GSLs correlated with those of the HPLC analysis of unlabelled GSLs. All tumors contained neutral GSL of the ganglio-series. Weakly metastatic tumor Eb showed neutral GSL patterns comparable to those from ConA-stimulated spleen cells, whereas strongly metastatic tumors ESb and MDAY-D2 had an enhanced expression of lactosylceramide. Gangliosides of metastatic ESb and MDAY-D2 had a higher degree of polarity than those of weakly metastatic Eb. Eb cells expressed primarily GM1. Metastasizing ESb and MDAY-D2 had significantly higher amounts of GM3, GM2 and GD1a. An unusual ganglioside, IV3GalNAc-GM1, was found in MDAY-D2 cells and ConA blasts. When the extent of label was compared in neutral GSLs and gangliosides, metastasizing ESb and MDAY-D2 were more heavily labelled in the ganglioside fraction (62%, 58%) than Eb (39%). ESb and MDAY-D2 also contained larger amounts of gangliosides than Eb.

Animals↗
PubMed1991

Clonal dominance of select subsets of viral Kirsten ras(+)-transformed 3T3 cells during tumor progression.

Long-term culturing of viral Kirsten-ras-oncogene (v-Ki-ras)-transformed BALB/c 3T3 cells (KiMSV) selectively enriches for cells which have deleted the viral oncogene. In contrast, v-Ki-ras in vivo is amplified and expression increased in all late-stage tumors and lung metastases relative to late-passage KiMSV cells being injected. The nature and significance of these selection processes, in terms of the v-Ki-ras gene, have been explored using genetically-tagged cells, as have the properties of v-Ki-ras- revertant subclones. Inoculation of KiMSV late-passage cells (containing less than 5% v-Ki-ras+ cells) into nude mice, generated primary and lung metastatic tumors with the v-Ki-ras gene at increased dosage in all tumors and their single-cell clones, isolated at both early and late stages of tumor development; this demonstrates early and specific in vivo selection for v-Ki-ras+ cells in both induction and progression of tumors in this system. v-Ki-ras- revertant subclones, isolated from late-passage KiMSV cells and inoculated individually into athymic nude mice, yielded tumors for only 1 of the 4 revertants, with no evidence for v-Ki-ras sequences in these tumor cells, thereby revealing a v-Ki-ras-independent mechanism for tumor formation in a small subset of revertant cells. Mixtures of the 4 subclones yielded tumors in all animals, although at a much longer latent period than observed with v-Ki-ras+ cells. Experiments with mixtures of v-Ki-ras- revertant cells and pSV2neo0tagged/v-Ki-ras+ cells (both complex NeoR cell mixtures and individual NeoR clones tested) at various cell ratios revealed clonal variability among v-Ki-ras+ cells for dominance during tumor formation. Moreover, the complex NeoR cell mixtures yielded both primary and metastatic tumors with simplified patterns of pSV2neo integration sites, suggesting that secondary genetic or epigenetic events, in addition to v-Ki-ras, contribute to the tumor-progressing phenotype. These experiments taken together demonstrate (a) clone-specific early selection of distinct v-Ki-ras+ cells amongst themselves and over v-Ki-ras- cells in both induction and progression of tumors, (b) reduced tumorigenic competence of v-Ki-ras- revertant cells, with a small subset displaying a v-Ki-ras-independent mechanism for tumor formation in this BALB/c 3T3 system, and (c) the significance of additional genetic or epigenetic events for tumor-progressing competence in unique subsets of v-Ki-ras+ cells.

Animals↗
PubMed1982

Experimental hematogenic metastases of malignant schwannoma in the rat.

To study development, growth patterns and morphology of metastatic schwannomas in an animal model, adult Lewis rats were injected intravenously with tissue culture cells derived from a malignant schwannoma induced in a female LEW/mai rat by transplacental administration of ethylnitrosourea (ENU). Groups of animals received a single injection of 0.1 x 10(5); 0.5 x 10(5); 1.0 x 10(5); 5.0 x 10(5); 10 x 10(5) or 100 x 10(5) cells via the femoral vein. The injections resulted in the development of metastatic tumors, primarily involving the lung in all animals. Lung metastases were observed in the form of microscopic and macroscopic peripheral subpleural tumors, central peribronchial and perivascular tumors, parenchymal tumors, diffuse intraalveolar infiltrates and intravascular tumor emboli which were growing. Animals receiving high dosages had a greater variety of forms of the metastatic growth in the lungs than those given low dosages. The animals which received the highest dose had the greatest degree of total lung tumor burden. In 36 of the 60 animals injected, metastatic tumors also developed in the pericardium. Thirteen animals developed metastatic tumors in the kidney, heart, ovary, adrenal, intestine or skeletal muscles. As the cell dosages were increased, more organs became involved, but no tumors developed in the brain.

Animals↗
PubMed1988

Magnetic resonance imaging in the diagnosis of tumors of the liver.

To evaluate the usefulness of magnetic resonance (MR) imaging in the diagnosis of liver tumors, MR imaging was performed in 70 patients, 30 with normal or cirrhotic liver, 15 with benign tumors and 25 with malignant tumors. MR imaging was carried out with a 0.5-Tesla superconducting magnet and was made using a spin-echo technique, from which T1 and T2-weighted images were obtained, and also T1 and T2 values were measured. Hemangiomas and cysts were demonstrated as sharply circumscribed homogeneous masses of low- or high-intensity on each image. Hepatomas were revealed as low-, iso- and high-intensity masses on both images. The minimum size of hepatoma detected, 1 cm in diameter, exhibited uniform intensity. Large hepatomas showed a mosaic pattern of different intensities, a low-intensity area around the mass, and a capsular pattern. The majority of metastatic tumors demonstrated a characteristic irregularity at the periphery of the mass. There were significant differences in T1 and T2 values between benign and malignant tumors. These results suggest that MR imaging is useful not only in the detection but also in the differentiation of liver tumors and can permit evaluation of the architecture of the tumor.

Adenocarcinoma↗
PubMed1987

Use of indium-111-labeled OC-125 monoclonal antibody in the detection of ovarian cancer.

This is a preliminary study to evaluate the utility of using the monoclonal antibody (CO-125) labeled with indium-111 to image recurrences of ovarian cancer. This technique has been investigated in 23 patients with ovarian cancer and the results have been compared with blood OC-125 levels, CT scans, and findings at second-look surgery. Following infusion of 1 mg of F(ab')2 fragments (1-2 mCi 111In), quantitative SPECT and planar imaging was obtained daily for 72 hr along with analysis of serum. The nuclear medicine scans of the tumor site recurrences were technically excellent. When compared to second-look laparotomy, there were 2 true negatives, 2 false positives, 14 true positives, and 2 false negatives by nuclear imaging. CT scans correlated less well with surgery, but serum OC-125 levels correlate more closely with nuclear scans and second-look surgery. Those with multiple small metastatic implants showed a pattern of diffuse uptake which increased with time, whereas those with nodal or larger recurrences showed a more focal uptake. The combination of favorable biodistribution and positive images, especially in patients with normal antigen levels and negative CT scans, suggests a role for OC-125 monoclonal antibody imaging in their clinical management. However, further investigation is needed to determine whether nuclear scans can replace second-look surgery. If it can show that enough 111In-labeled antibody accumulates in the tumor site to justify radioimmunotherapy, then 90Y (a pure beta emitter) could be exchanged for 111In. This is potentially a method of radioimmunotherapy for recurrent ovarian carcinoma.

Adult↗
PubMed1987

Lack of efficacy of lymphoscintigraphy in detecting axillary lymph node metastases from breast cancer.

Preoperative detection of metastases in regional lymph nodes should constitute a fundamental step towards a better management of breast cancer. The National Cancer Institute of Milan has traditionally been engaged in this particular problem, that is, the search for a new imaging technique for detecting lymph nodal metastases from breast cancer. In 1984 axillary lymphoscintigraphy was performed on 26 patients with operable breast cancer by periareolar injection of 100 mu Ci of 99mTc sulphur microcolloid. The regional lymph nodes were identified as spot areas and a comparison was made between the number of primary draining axillary lymph nodes and their pathological examination. In only 2 of the 26 patients have more than 3 spot areas been revealed by axillary scintiscan, but this finding did not correspond to metastatic invasion. The lymphoscintigraphy pattern of the other 24 patients did not suggest any pathological condition. From our experience the method does not appear to help either a precise diagnosis of breast disease or the definition of the extent of mammary cancer.

Adult↗
PubMed2026

Expression patterns of potential targets for antibody-directed therapy in metastatic castration-resistant prostate cancer patients.

INTRODUCTION: Survival in metastatic castration-resistant prostate cancer (mCRPC) patients remains limited and treatment is complicated by tumor heterogeneity. As antibody-based therapeutics emerge, identifying actionable antigen targets and patient subgroups most likely to benefit is essential. MATERIALS & METHODS: Gene expression of 62 antibody-targetable proteins was analyzed in 296 mCRPC biopsies. These genes encode proteins targeted by approved or investigational antibody-based cancer therapeutics. Associations between target expression with genomic classifications and transcriptomic subtypes were evaluated. Target expression was also assessed in tumors with low expression of established mCRPC targets. Subgroup-specific targets were validated in an independent cohort and single-cell transcriptomics. RESULTS: Established targets KLK2, FOLH1 (PSMA) and STEAP1 showed the highest median expression across the cohort. Target expression did not correlate with genomic classifications, including homologous recombination deficiency, microsatellite instability, CDK12, TP53, PTEN or AR alterations Target expression did associate with transcriptomic subtypes: CRPC-AR (driven by androgen receptor-signaling) and CRPC-SCL (stem cell-like features, AP-1/YAP/TAZ-driven), displayed the highest expression of multiple targets, including KLK2, FOLH1, and SLC44A4. CRPC-NE (neuroendocrine phenotype) showed heterogeneous expression, with high CD46 expression, whereas CRPC-WNT (Wnt-signaling driven) generally showed low target expression. Notably, CD46 was highly expressed in tumors with low KLK2, FOLH1, and STEAP1 expression, a subgroup associated with poor prognosis. CONCLUSIONS: Although several antibody targets showed broad expression in mCRPC-tumors, expression varied by transcriptomic subtype. Subgroups such as CRPC-WNT expressed fewer targets, suggesting the need for alternative therapeutic strategies. CD46 emerged as a promising target, with wide expression across multiple subtypes, including clinically challenging CRPC-NE and mCRPC tumors lacking expression of established targets.

Humans↗
PubMed2004

Association of E-cadherin and beta-catenin immunoexpression with clinicopathologic features in primary ovarian carcinomas.

Epithelial cadherin forms a complex with alpha-, beta-, and gamma-catenin proteins. Reduced expression of E-cadherin-catenins has been shown in human carcinomas and is associated with low histologic differentiation, increased risk of invasion, and metastatic disease. The immunoexpression pattern of E-cadherin and beta-catenin (reduced versus preserved phenotype) was evaluated in 104 primary ovarian carcinomas and related to clinicopathologic features of the tumors. The immunoexpression pattern of E-cadherin was associated with International Federation of Gynaecology and Obstetrics (FIGO) staging (P = 0.043), histologic subtype (P = 0.001), peritoneal metastasis (P = 0.006), and residual tumor (P = 0.036). The reduced phenotype of E-cadherin that was observed in 64% of the carcinomas (67/104) was associated with advanced stage tumors, serous carcinomas, presence of peritoneal metastasis, and residual tumor larger than 2 cm. The immunoexpression pattern of beta-catenin was associated with histologic subtype (P = 0.005), tumor differentiation (P = 0.025), and peritoneal metastasis (P = 0.041). The reduced phenotype of beta-catenin that was observed in 74% of the carcinomas (77/104) was associated with advanced stage tumors, poorly differentiated serous and clear cell carcinomas, presence of peritoneal metastasis, and residual tumor. The immunoexpression pattern of E-cadherin was correlated with beta-catenin (P = 0.001). The reduced phenotype for both E-cadherin and beta-catenin was associated with histologic subtype (P < 0.001) and peritoneal metastasis (P = 0.001). In conclusion, the immunohistochemical profile of E-cadherin and beta-catenin may be useful in identifying a particular subpopulation of ovarian cancer patients who are characterized by an adverse clinical outcome, because the reduced phenotype of these molecules was associated with poor tumor differentiation, peritoneal metastasis, and advanced FIGO stage tumors.

Adenocarcinoma↗
PubMed1999

Genetic differences in endocrine pancreatic tumor subtypes detected by comparative genomic hybridization.

The molecular pathogenesis as well as histogenesis of endocrine pancreatic tumors (EPTs) is not well understood, and the clinical behavior of EPTs is difficult to predict using current morphological criteria. Thus, more accurate markers of risk and better understanding of tumor initiation and progression are needed to allow a precise classification of EPTs. We have studied 44 benign and malignant EPTs by comparative genomic hybridization to correlate the overall number of genetic alterations with clinical and histopathological parameters and to identify chromosomal regions which might harbor genes involved in EPT pathogenesis and progression. Aberrations were found in 36 EPTs, and chromosomal losses (mean, 5.3) were slightly more frequent than gains (mean, 4. 6). The most frequent losses involved Y (45% of male EPTs), 6q (39%), 11q (36%), 3p, 3q, 11p (each 30%), 6p (27%), and 10q and Xq (each 25%), whereas most common gains included 7q (43%), 17q (41%), 5q and 14q (each 32%), 7p, 9q, 17p, 20q (each 27%), and 12q and Xp (each 25%). A correlation was found between the total number of genetic changes per tumor and both tumor size and disease stage. In particular, losses of 3p and 6 and gains of 14q and Xq were found to be associated with metastatic disease. Furthermore, characteristic patterns of genetic changes were found in the various EPT subtypes, eg, 6q loss in malignant insulinomas, indicating that these groups might evolve along genetically different pathways. The highlighted genetic aberrations, including the newly found involvement of 6q losses and sex chromosome alterations, should stimulate the further analysis of these chromosomal regions, which may lead to the discovery of novel genes important in the tumorigenesis and evolution of EPTs.

Chromosome Aberrations↗
PubMed1991

Acute renal failure secondary to carcinomatous lymphatic metastases to kidneys.

We report a rare case of acute renal failure secondary to bilateral renal parenchymal metastases from carcinoma. Despite clinical investigation the cause of the renal failure remained undiagnosed and was discovered only upon microscopy at autopsy, which revealed metastatic gastric adenocarcinoma. The pattern of tumor infiltration was predominantly lymphatic involvement limited to the vascular bundles at the corticomedullary junction, and the lymphatics adjacent to the calices and pelves. The significance of lymphatic obstruction in the pathogenesis of renal failure is discussed. Renal parenchymal metastases should be considered in the differential diagnosis of acute renal failure in patients with carcinoma.

Acute Kidney Injury↗
PubMed2004

Is there a favorable subset of patients with prostate cancer who develop oligometastases?

OBJECTIVE: To analyze, retrospectively, the patterns and behavior of metastatic lesions in prostate cancer patients treated with external beam radiotherapy and to investigate whether patients with < or =5 lesions had an improved outcome relative to patients with >5 lesions. METHODS AND MATERIALS: The treatment and outcome of 369 eligible patients with Stage T1-T3aN0-NXM0 prostate cancer were analyzed during a minimal 10-year follow-up period. All patients were treated with curative intent to a mean dose of 65 Gy. The full history of any metastatic disease was documented for each subject, including the initial site of involvement, any progression over time, and patient survival. RESULTS: The overall survival rate for the 369 patients was 75% at 5 years and 45% at 10 years. The overall survival rate of patients who never developed metastases was 90% and 81% at 5 and 10 years, respectively. However, among the 74 patients (20%) who developed metastases, the survival rate at both 5 and 10 years was significantly reduced (p <0.0001). The overall survival rate for patients who developed bone metastases was 58% and 27% at 5 and 10 years, respectively, and patients with bone metastases to the pelvis fared worse compared with those with vertebral metastases. With regard to the metastatic number, patients with < or =5 metastatic lesions had superior survival rates relative to those with >5 lesions (73% and 36% at 5 and 10 years vs. 45% and 18% at 5 and 10 years, respectively; p = 0.02). In addition, both the metastasis-free survival rate and the interval measured from the date of the initial diagnosis of prostate cancer to the development of bone metastasis were statistically superior for patients with < or =5 lesions compared with patients with >5 lesions (p = 0.01 and 0.02, respectively). However, the survival rate and the interval from the date of diagnosis of bone metastasis to the time of death for patients in both groups were not significantly different, statistically (p = 0.17 and 0.27, respectively). CONCLUSIONS: Patients with < or =5 metastatic sites had significantly better survival rates than patients with >5 lesions. Because existing sites of metastatic disease may be the primary sites of origin for additional metastases, our findings suggest that early detection and aggressive treatment of patients with a small number of metastatic lesions is worth testing as an approach to improving long-term survival.

Aged↗
PubMed1991

In vitro differentiation of rhabdomyosarcomas induced by nickel or by Moloney murine sarcoma virus.

In vitro cultures and clonal derivatives have been established from rat rhabdomyosarcomas induced by Moloney-Murine Sarcoma Virus (MSV) or by nickel sulfide; differentiation ability has been studied as expression of desmin, embryonic and adult myosin isoforms, alpha-actin isoforms and cellular fusion. The two rhabdomyosarcoma models showed different levels of myogenic differentiation. Multinucleated myotube-like structures were frequently observed in cultures derived from nickel-induced tumours. Desmin was present in 50-80% of cells and embryonic myosin in up to 10%. In MSV-tumour-derived cultures and in their metastases or clonal derivatives two cell types are present in different ratios: spindle-shaped cells, adherent to plastic surfaces, and rounded cells, loosely attached or floating free in the medium. These cultures showed features of myogenic differentiation (10-80% desmin-positive cells), but embryonic myosin expression and production of multinucleated myotube-like structures were very rare events. Cultures from autochthonous lymph node and lung metastatic cells showed similar patterns of differentiation. Retinoic acid increased differentiated features (myotube formation and embryonic myosin expression) only in nickel-induced rhabdomyosarcoma cells. The two models described here mimic the heterogeneity in differentiation pattern found among human rhabdomyosarcomas. Myogenic differentiation ability was retained at a good level by nickel-induced tumours, whereas it was strongly impaired in MSV-induced tumours.

Animals↗
PubMed1993

Stromelysin 3 belongs to a subgroup of proteinases expressed in breast carcinoma fibroblastic cells and possibly implicated in tumor progression.

The expression of the stromelysin 3 (ST3) gene, which encodes a putative matrix metalloproteinase, was studied during breast cancer progression. The ST3 gene is expressed in all invasive breast carcinomas, in a number of their metastases, and in some in situ carcinomas where the probability of detecting ST3 transcripts correlates with the known risk of these carcinomas to become invasive. ST3 RNA and protein were specifically detected in fibroblastic cells immediately surrounding the neoplastic cells in both primary and metastatic tumors. This expression pattern distinguishes the ST3 gene from other matrix metalloproteinase genes, most notably from the 72-kDa type IV collagenase gene, which can be expressed in fibroblastic cells distributed throughout the stroma of primary breast carcinomas. Furthermore, high levels of 72-kDa type IV collagenase, but not of ST3 transcripts, are detected in benign breast fibroadenomas. Interestingly, the urokinase and ST3 genes exhibit very similar patterns of expression in breast carcinomas, which suggests that their products may cooperate during cancer progression.

Adenoma↗
PubMed2003

Microglandular adenosis with transition into adenoid cystic carcinoma of the breast.

Microglandular adenosis (MGA) is a well-recognized, if rare and incompletely characterized, entity in which carcinoma is rarely thought to develop. We report 17 cases in which patterns of adenoid cystic carcinoma (ACC) coexisted with MGA. Immunocharacterization with beta-catenin, E-cadherin, cytokeratins (AE1/AE3), epithelial membrane antigen, S-100 protein, smooth muscle actin, and vimentin was also performed. Most cases had areas of invasive ACC characterized by its defining dual-lumen types. Some cases of ACC appeared to have expanded glands intermingled within the MGA, whereas in other cases ACC formed a transition with the characteristic small, gland-like spaces of MGA. MGA and "atypical MGA" stained irregularly and similarly to that seen in myoepithelium with the three markers of myoepithelial cells in breast: S-100 protein, smooth muscle actin, and vimentin. These markers were also positive in the more solid elements of the ACC. Our study suggests that ACC may develop in a background of and in continuity with MGA. Altered myoepithelial cells appear to be the major neoplastic element in both ACC and "atypical MGA." "Atypical MGA" with transition to ACC may show histologic patterns and an immunohistochemical profile similar to that of ACC. These lesions might be best interpreted as ACC in situ. Both MGA and ACC of the breast grow in an expansile and diffusely infiltrative pattern without having significant metastatic capacity. Their unusual interaction with the surrounding stroma may play a role in this benign biologic behavior.

Adult↗