乳腺错构瘤X线及病理特征分析

目的：探讨乳腺错构瘤的病理及影像学特征。方法：对11例乳腺错构瘤患者的临床特征、X线征象及病理表现进行回顾性分析。结果：患者平均年龄为46岁（26-58岁）,10例可触及肿块（9例患者自己发现,1例体检摄片时发现）,还有1例未能触及肿块。左乳7例,右乳4例,5／11（45．5％）肿块位于外上象限。11例钼靶X线平片均发现乳腺肿块,多数肿块呈卵圆形,边界清楚。肿块平均最大直径为6．Ocm（2．5-13．0cm）,6／11（54．5％）肿块呈混合密度影。4／11例（36．4％）术前X线确诊。镜下：肿瘤由数量不等、杂乱无章的乳腺导管、小叶和成熟的脂肪细胞及纤维纽织混杂组成。结论：混合密度影是其特异性X线表现,不同个体肿瘤各成分比例的不同导致X线表现差异较大。     

Fine needle aspiration cytology of mesenchymal hamartoma of the liver. A case report

BACKGROUND: Mesenchymal hamartoma (MH) of the liver constitutes the third or fourth most common tumor of the liver in childhood and occurs most commonly in the first two years of life. MHs of the liver are seldom aspirated, and reports on the role of fine needle aspiration (FNA) in the diagnosis of MH are scarce. Clinically, cytologically and even histologically, MH can be mistaken for a number of reactive and neoplastic hepatic lesions that may occur in children under 2 years of age. CASE: A 10-month-old Pakistani female presented with a history of a right-sided, nonpainful abdominal swelling. Abdominal computed tomography showed a large, partly solid and partly cystic, heterogeneous hepatic mass. FNA cytology showed clusters of both epithelial and mesenchymal/spindle-shaped cells with pieces of loose connective tissue. A cytologic differential diagnosis of mesenchymal hepatic hamartoma and hepatoblastoma of the possible mixed mesenchymal/epithelial subtype was rendered. The histopathologic diagnosis of the resected tumor mass was benign mesenchymal hamartoma of the liver. CONCLUSION: In children under 2 years of age who present with partly solid and partly cystic hepatic masses, the possibility of MH of the liver should be considered. FNA has a role in the diagnosis of MH. The cytopathologist should be aware of the patient's age, radiologic features and cytologic appearances of this rare, benign neoplasm. Histologic examination of tru-cut biopsies and immunohistochemical stains can help to exclude other pediatric neoplasms that may show cytologic features similar to or mimicking those of MH.     

Ectopic lesions as potential pitfalls in fine needle aspiration cytology: a report of 3 cases derived from the thyroid, endometrium and breast

BACKGROUND: Ectopic lesions are rarely encountered. Those that are derived from thyroid, breast, endometrium and salivary glands present with palpable masses that can mimic malignancy. Fine needle aspiration cytology (FNAC) is a practical procedure for the differential diagnosis of such lesions but can reveal surprising images for a cytopathologist. CASES: Three cases of discrete, ectopic lesions at different locations occurred. Case 1 was a 27-year-old woman. Upon diagnosis of a submandibular mass with a diameter of 1 cm, FNAC was performed. The smears showed crowded thyroid follicular cells comprising papillary clusters. A cytologic diagnosis of papillary thyroid lesion was rendered, Histopathology revealed that this lesion was ectopic thyroid tissue with focal chronic thyroiditis. Case 2 was a 38-year-old woman who presented with a painful mass with a diameter of 2.5 cm in the abdominal wall. The patient had undergone cesarean section 3 years earlier. The case was diagnosed on FNAC as low grade malignancy in which an adenocarcinoma/mesenchymal tumor distinction could not be made. The pathologic examination revealed endometriosis. Case 3 was a 31-year old woman who presented with a palpable nodule in the axillary region with a diameter of 1 cm. The patient had given birth 1 month earlier and was nursing. An FNAC diagnosis of lactation ectopic breast tissue was made. The mass disappeared by the end of lactation. CONCLUSION: FNAC of ectopic lesions may prove to be a diagnostic pitfall for cytopathologists. A cytopathologist who encounters a cellularpicturefrom a lesion that is outside the normal anatomic location must use a cautious diagnostic approach. Unless there are clear findings, the cytopathologist must refrain from a diagnosis of malignancy.     

Papillary neoplasms of the breast: clues in fine needle aspiration cytology

Papillary neoplasms of the breast include a wide spectrum of mammary lesions. The differential diagnosis of benign and malignant lesions can be problematic not only cytologically, but also histopathologically. Aspiration smears can demonstrate that cytological differentiation is feasible. A retrospective study of 30 cases of papillary tumour of the breast, 15 papillary carcinomas and 15 papillomas, was performed to find the cytological differences between the pathologies. Cytological samples of papillary carcinomas were characterized by an abundance of cellular material, three-dimensional papillary clusters without fibrovascular connective tissue cores, small papillae arranged in cell balls, tall columnar cells and isolated naked nuclei. Numerous haemosiderin-laden macrophages were seen. There were no eosinophilic bipolar cytoplasmic granules, bipolar naked nuclei or apocrine metaplasia. In the papillomas there was less material; the papillae had cohesive stalks surrounded by columnar cells in a honeycomb pattern. We also found fewer small papillae and isolated columnar cells. In addition, the presence of apocrine metaplasia and bipolar naked nuclei was noted. We suggest that papillary carcinoma of the breast can be diagnosed by cytology and differentiated from papilloma.     

Fine needle aspiration cytodiagnosis of secretory carcinoma of the breast

Secretory carcinoma (SC) of the breast is a rare variant of breast malignancy and its cytological features in fine needle aspirates have only recently been described. In this communication, our experience with four cases of SC of the breast is presented in which the diagnosis was established on fine needle aspiration cytology (FNAC). In all cases, the samples were cellular and featured diffuse, prominent, intracytoplasmic vacuoles and secretion in malignant cells and occasional signet-ring like forms. The cytodiagnosis of SC in all the cases correlated with subsequent examination of cell blocks of the aspirate and tissue. Cytochemical stains showed diffuse positivity for mucin by alcian blue stain in the vacuolated cells which was periodic acid-Schiff positive and resistant to diastase digestion. Oil-red O staining was negative. Immunopositivity to carcinoembryonic antigen, cytokeratin (CAM 5.2), B72.3 and epithelial membrane antigen was found in malignant cells. The cytodiagnostic criteria for SC of the breast, characteristic cytological features which are useful in a correct FNAC diagnosis and differentiation from other pertinent breast carcinomas, are discussed.     

SWI/SNF Chromatin-Remodeling Factor Smarcd3/Baf60c Controls Epithelial-Mesenchymal Transition by Inducing Wnt5a Signaling

We previously identified a gene signature predicted to regulate the epithelial-mesenchymal transition (EMT) in both epithelial tissue stem cells and breast cancer cells. A phenotypic RNA interference (RNAi) screen identified the genes within this 140-gene signature that promoted the conversion of mesenchymal epithelial cell adhesion molecule-negative (EpCAM⁻) breast cancer cells to an epithelial EpCAM^+/high phenotype. The screen identified 10 of the 140 genes whose individual knockdown was sufficient to promote EpCAM and E-cadherin expression. Among these 10 genes, RNAi silencing of the SWI/SNF chromatin-remodeling factor Smarcd3/Baf60c in EpCAM⁻ breast cancer cells gave the most robust transition from the mesenchymal to epithelial phenotype. Conversely, expression of Smarcd3/Baf60c in immortalized human mammary epithelial cells induced an EMT. The mesenchymal-like phenotype promoted by Smarcd3/Baf60c expression resulted in gene expression changes in human mammary epithelial cells similar to that of claudin-low triple-negative breast cancer cells. These mammary epithelial cells expressing Smarcd3/Baf60c had upregulated Wnt5a expression. Inhibition of Wnt5a by either RNAi knockdown or blocking antibody reversed Smarcd3/Baf60c-induced EMT. Thus, Smarcd3/Baf60c epigenetically regulates EMT by activating WNT signaling pathways.     

Periostin Contributes to the Acquisition of Multipotent Stem Cell-Like Properties in Human Mammary Epithelial Cells and Breast Cancer Cells

Periostin (POSTN), a recently characterised matricellular protein, is frequently dysregulated in various malignant cancers and promotes tumor metastatic growth. POSTN plays a critical role in the crosstalk between murine breast cancer stem cells (CSCs) and their niche to permit metastatic colonization. However, whether pro-metastatic capability of POSTN is associated with multipotent potentials of mesenchymal stem cells (MSCs) has not been documented. Here we demonstrate that POSTN promotes a stem cell-like trait and a mesenchymal phenotype in human mammary epithelial cells and breast cancer cells. Interestingly, ectopic overexpression of POSTN or recombinant POSTN treatment can induce human mammary epithelial cells and breast cancer cells differentiation into multiple cell lineages that recapitulate part of the multilineage differentiation potentials of MSCs. Moreover, POSTN is highly expressed in bone marrow-derived MSCs and their derived adipocytes, chondrocytes, and osteoblasts in vitro. Furthermore, POSTN promotes the growth of xenograft tumors in vivo. POSTN-overexpressing human mammary epithelial cells enhance breast tumor growth and metastasis. These data thus provide evidence of a new role for POSTN in mammary epithelial neoplasia and metastasis, suggesting that epithelial cancer cells might acquire CSC-like traits and a mesenchymal phenotype, as well as the multipotent potentials of MSCs to promote tumorigenesis and metastasis. Therefore, targeting POSTN and other extracellular matrix components of tumor microenvironment may help to develop new therapeutical strategies to inhibit tumor metastasis.     

Human breast milk is a rich source of multipotent mesenchymal stem cells

Putative stem cells have been isolated from various tissue fluids such as synovial fluid, amniotic fluid, menstrual blood, etc. Recently the presence of nestin positive putative mammary stem cells has been reported in human breast milk. However, it is not clear whether they demonstrate multipotent nature. Since human breast milk is a non-invasive source of mammary stem cells, we were interested in examining the nature of these stem cells. In this pursuit, we could succeed in isolating and expanding a mesenchymal stem cell-like population from human breast milk. These cultured cells were examined by immunofluorescent labeling and found positive for mesenchymal stem cell surface markers CD44, CD29, SCA-1 and negative for CD33, CD34, CD45, CD73 confirming their identity as mesenchymal stem cells. Cytoskeletal protein marker analysis revealed that these cells expressed mesenchymal stem cells markers, namely, nestin, vimentin, smooth muscle actin and also manifests presence of E-Cadherin, an epithelial to mesenchymal transition marker in their early passages. Further we tested the multipotent differentiation potential of these cells and found that they can differentiate into adipogenic, chondrogenic and oesteogenic lineage under the influence of specific differentiation cocktails. This means that these mesenchymal stem cells isolated from human breast milk could potentially be “reprogrammed” to form many types of human tissues. The presence of multipotent stem cells in human milk suggests that breast milk could be an alternative source of stem cells for autologous stem cell therapy although the significance of these cells needs to be determined.     

Myospherulosis. Fine needle aspiration cytologic findings in 19 cases

An analysis was made of 19 cases of myospherulosis seen on fine needle aspirates of mammary and subcutaneous tissue masses. Myospherulosis, best seen with the Papanicolaou stain, appeared as 4 microns to 7 microns spherules that were homogeneously smooth or contained one or more internal dense bodies. The spherules were dispersed singly or aggregated into sac-like structures. Myospherulosis accompanied 16 benign and 3 malignant conditions. In two aspirates, myospherulosis was seen simultaneously with breast carcinoma; in another, fat necrosis with myospherulosis masked an underlying breast malignancy. In 10 of the 12 aspirates from patients with previous tissue trauma, it accompanied evidence of fat necrosis and mesenchymal repair; in 4 aspirates, no other underlying condition was apparent. These findings indicate that myospherulosis is not an uncommon finding in fine needle aspirates of fatty sites; it often accompanies fat necrosis and mesenchymal repair. The presence of myospherulosis in aspirates of clinically suspicious masses does not exclude an underlying malignancy.     

Role of fine needle aspiration cytology in the diagnosis of soft tissue tumours

Fine needle aspiration cytology (FNAC) is a widely accepted safe, simple and rapid diagnostic procedure used in the examination of neoplastic and non‐neoplastic lesions of various locations. Since its introduction, FNAC has developed into an effective diagnostic tool practiced in a large majority of medical centres evaluating and treating oncological patients. The role of FNAC has been limited in the examination of primary soft tissue lesions, however, as many physicians working in this area recommended against using FNAC. An increasing use of minimally invasive diagnostic procedures in the last decade has resulted in a better acceptance of FNAC as a first‐line approach or as a complementary tool to core needle biopsy in the diagnosis of musculoskeletal lesions. This review discusses the role and value of FNAC in the evaluation and treatment of soft tissue tumours based on the experience gathered over the course of 48 years at the Sarcoma Center in Lund, Sweden. FNAC reports most often provide diagnostic information allowing the initiation of treatment or, when definitive diagnosis cannot be rendered from a cytological examination, guiding the continued diagnostic investigation. The main advantages of soft tissue FNAC are good sensitivity and specificity, low morbidity, speed of diagnosis, and low cost/benefit ratio. The most important disadvantages stem from limited experience in cytological diagnosis of soft tissue tumours and a lack of standardised and uniform reporting system for soft tissue FNAC.     

Expression and Functional Role of Sprouty-2 in Breast Morphogenesis

Branching morphogenesis is a mechanism used by many species for organogenesis and tissue maintenance. Receptor tyrosine kinases (RTKs), including epidermal growth factor receptor (EGFR) and the sprouty protein family are believed to be critical regulators of branching morphogenesis. The aim of this study was to analyze the expression of Sprouty-2 (SPRY2) in the mammary gland and study its role in branching morphogenesis. Human breast epithelial cells, breast tissue and mouse mammary glands were used for expression studies using immunoblotting, real rime PCR and immunohistochemistry. Knockdown of SPRY2 in the breast epithelial stem cell line D492 was done by lentiviral transduction of shRNA constructs targeting SPRY2. Three dimensional culture of D492 with or without endothelial cells was done in reconstituted basement membrane matrix. We show that in the human breast, SPRY2 is predominantly expressed in the luminal epithelial cells of both ducts and lobuli. In the mouse mammary gland, SPRY2 expression is low or absent in the virgin state, while in the pregnant mammary gland SPRY2 is expressed at branching epithelial buds with increased expression during lactation. This expression pattern is closely associated with the activation of the EGFR pathway. Using D492 which generates branching structures in three-dimensional (3D) culture, we show that SPRY2 expression is low during initiation of branching with subsequent increase throughout the branching process. Immunostaining locates expression of phosphorylated SPRY2 and EGFR at the tip of lobular-like, branching ends. SPRY2 knockdown (KD) resulted in increased migration, increased pERK and larger and more complex branching structures indicating a loss of negative feedback control during branching morphogenesis. In D492 co-cultures with endothelial cells, D492 SPRY2 KD generates spindle-like colonies that bear hallmarks of epithelial to mesenchymal transition. These data indicate that SPRY2 is an important regulator of branching morphogenesis and epithelial to mesenchymal transition in the mammary gland.     

Evaluation of aspiration cytology of ovarian masses with histopathological correlation

T. Sood, U. Handa, H. Mohan and P. Goel
Evaluation of aspiration cytology of ovarian masses with histopathological correlation Objectives: To evaluate the efficacy and diagnostic accuracy of fine needle aspiration cytology (FNAC) in distinguishing non‐neoplastic and neoplastic ovarian lesions and to determine reliable cytological criteria for typing neoplastic ovarian masses into benign and malignant tumours and their subtypes. Methods: FNAC was performed on 50 patients diagnosed as having an ovarian mass clinically and/or ultrasonographically. Detailed history, clinical examination and ultrasound findings in each case were recorded. The cytological diagnoses were categorized as neoplastic and non‐neoplastic and further into benign and malignant neoplasms. These cytological diagnoses were then compared subsequently with the histopathological diagnoses. Results: The study material consisted of 57 aspirates from 50 patients. A comparison of cytological findings with the histological diagnosis was possible in 53 aspirates; in the remaining four cases (7%) the smears were acellular. On cytology, 31 lesions were diagnosed as neoplastic and 22 as non‐neoplastic. The overall sensitivity of cytology in diagnosing neoplastic and non‐neoplastic ovarian lesions was 93.9% and the specificity was 100%. The positive predictive value was 100% and negative predictive value 90.9%. The overall diagnostic accuracy was 96.2 %. Conclusion: FNAC of ovarian masses is a minimally invasive procedure that can differentiate neoplastic from non‐neoplastic ovarian lesions. It may help avoid unnecessary operations and preserve the reproductive ability in young patients. Furthermore, it also enables a satisfactory sub‐categorization of ovarian tumours, which facilitates the choice of appropriate therapy.     

Cytomorphological spectrum in scar endometriosis: a study of eight cases

OBJECTIVE: Endometriosis due to ectopic endometrial tissue that responds to hormonal stimulation and is extremely rare in a surgical scar appearing in 0.1% of women who have undergone Caesarean section. Fine needle aspiration cytology (FNAC) can be a valuable diagnostic aid in the evaluation of these subcutaneous abdominal masses. METHODS: We present the cytomorphological spectrum in eight cases of abdominal wall endometriosis diagnosed by FNAC over a 6-year period (June 1998-June 2004) in Mubarak Al-Kabeer Hospital (Kuwait). The patients ranged from 27 to 56 years of age. Seven had a prior Caesarean section and one had a hysterectomy for fibroid. They presented 3-8 years later with nodules in/near the abdominal scar. Five cases presented with a painful nodule, fluctuant with the menstrual cycle. RESULTS: Cytological findings comprised epithelial clusters and fusiform stromal cells with numerous haemosiderin-laden macrophages. Mild to moderate epithelial atypia was observed in three cases. A diagnosis of endometriosis was rendered in all the eight cases and tissue was available in four cases. CONCLUSIONS: Endometriotic nodules need to be differentiated from other benign/malignant masses and evaluated for possible malignant transformation. FNAC provides a safe and effective tool for diagnosis thereby obviating the need for other procedures.     

Sustained co-cultivation with human placenta-derived MSCs enhances ALK5/Smad3 signaling in human breast epithelial cells,leading to EMT and differentiation

The interaction between mammary epithelial cells and their surrounding microenvironment are important in the development of the mammary gland. Thus, mesenchymal stem cells (MSCs), which retain pluripotency for various mesenchymal lineages, may provide a permissive environment for the morphologic alteration and differentiation of mammary epithelial cells. To this end, we investigated whether the interactions between mammary epithelial cells and human placenta-derived MSCs (hPMSC) affect the morphology, proliferation, and differentiation of epithelial cells in a co-culture system. We show that after co-culture with hPMSCs, human mammary epithelial cell lines (MCF-10F and HEMC) underwent significant morphologic alterations and a dramatic increase in ductal–alveolar branching, which was accompanied by a decrease or loss of the epithelial marker E-cadherin and a gain of the mesenchymal markers, α-SMA and vimentin. MCF-10F and HEMC proliferation was also inhibited in the presence of hPMSCs, and this retardation in growth was due to cell cycle arrest. Furthermore, in MCF-10F and HMEC cells, hPMSCs induced the production of lipid droplets, milk fat globule protein, and milk protein lactoferrin, which are markers of functional mammary differentiation. We also noticed an elevation in ALK5 and phosphorylated Smad3 protein levels upon hPMSC co-culture. Strikingly, the changes in morphology, proliferation, and differentiation were reversed by treatment with ALK5 or Smad3 knockdown in MCF-10F/hPMSC co-cultures. Collectively, our findings suggest that co-cultivation with hPMSCs leads to epithelial to mesenchymal transition (EMT) and differentiation of human breast epithelial cells through the ALK5/Smad3 signaling pathway.     

Daunorubicin-induced DNA lesions in isolated rat hepatocytes and mammary epithelial cells

Daunorubicin, an anticancer drug, induces primarily mammary adenocarcinoma in Sprague-Dawley rats. We investigated daunorubicin-induced DNA lesions in enzymatically isolated mammary epithelial cells and hepatocytes from 7-8-week-old female Sprague-Dawley rats. Differences were observed in the type and quantity of DNA lesions in mammary epithelial cells and hepatocytes as determined by alkaline elution analysis. DNA single-strand breaks and proteinase-K-sensitive cross-linking lesions were observed in mammary epithelial cells. Hepatocytes appeared to have significantly lower relative frequencies of single-strand breaks than mammary epithelial cells when treated with daunorubicin (1.5-10.0 micrograms/10(6) cells). Hepatocytes displayed two types of cross-link. One form was sensitive to proteinase-K digestion, whereas the other form was insensitive. The metabolism of daunorubicin to the aglycone metabolites was substantially lower in mammary cells than in hepatocytes. However, the total uptake of the drug was similar in these two cell types. A metabolite, 7-deoxydaunorubicinol aglycone, was unable to induce single-strand breaks or cross-linking lesions in mammary epithelial cells. Both cell types exhibited a similar ability to repair radiation-induced single-strand breaks of DNA. However, the mammary cells may be less able to repair daunorubicin-mediated DNA damage. These results revealed that mammary epithelial cells are less able to metabolize the active mutagen/carcinogen, daunorubicin, than are hepatocytes. This, coupled with the observations of greater apparent DNA damage in mammary cells, may be of primary importance in the drug-induced carcinogenicity in the rat mammary tissue.     

Cytokeratin profile of immunomagnetically separated epithelial subsets of the human mammary gland

Summary We have used enzymatic and immunomagnetic techniques for the physical separation of the basal and luminal epithelium of the human mammary gland. Immediately after tissue dissociation and cell sorting, we have examined the steady-state CK composition of these cells individually by direct two-dimensional gel electrophoresis of intermediate filament extracts. Our results demonstrate that cytokeratins typical of simple and stratified epithelial cells are simultaneously expressed by both mammary epithelial subclasses in vivo. Moreover, the entire spectrum of cytokeratins seen in vivo is also maintained in short-term cultures of human mammary epithelium. A comparison of the data obtained by direct cytokeratin analysis with published indirect immunolocalization studies is presented. The ability to isolate purified epithelial subsets from normal human breast tissue by a simple immunomagnetic procedure demonstrated here can facilitate the development of relevant model systems for studying the regulatory components in growth, differentiation and malignant transformation of the human breast.     

Ultrasonographically and stereotactically guided fine-needle aspiration cytology of non-palpable breast lesions: cyto-histological correlation

Objective:  To determine the diagnostic accuracy of ultrasonographically (US) and stereotactically guided fine needle aspiration cytology (FNAC) for the diagnosis of non-palpable breast lesions.
Patients and methods:  From January 2002 to December 2004, 470 women with 478 mammographically detected non-palpable breast lesions had US or stereotactically guided FNAC of the breast lesion. Subsequent histological evaluation of the same lesion was performed at the Institute of Oncology Ljubljana, Slovenia. The correlation between the original cytological and histological diagnosis was assessed and the sensitivity, specificity, positive predictive value and negative predictive value were calculated.
Results:  Among US-guided FNACs, 144 (53.5%) were histologically verified benign lesions and 125 (46.5%) were carcinomas. Cytological diagnoses were: true positive (TP) in 63 cases (50.4%), suspicious in 35 (28%), false negative (FN) in eight (6.4%), and in 19 (15.2%) cases, the material was inadequate for diagnosis. In the stereotactically guided FNAC group, there were 209 women with 209 lesions, with 95 (45%) histologically proven carcinomas and 114 (55%) benign lesions. Cytological diagnoses were TP in 49 (51.6%) cases, true suspicious in 21 (22.1%), FN in nine (9.5%), and in 16 (16.8%) cases, the material was not adequate for the diagnosis.
Conclusion:  The sensitivity of 88.7% and specificity of 98.6% for US-guided FNAC and 84.5% and 100% for stereotactically guided FNAC, respectively, suggest that clinicians can rely upon cytological diagnosis for planning further management of women with non-palpable breast lesions.     

Surviving without oxygen: Hypoxia regulation of mammary morphogenesis and anoikis

Tumor hypoxia correlates with resistance to chemotherapy, increased incidence of metastasis and poor clinical prognosis. Early breast cancer lesions, such as carcinoma in situ, characterized by filled lumens, are often associated with hypoxic markers. However, the contribution of hypoxia to changes in tissue architecture in early pre-malignant lesions is not well defined. Using three-dimensional basement membrane cultures of mammary epithelial cells, we recently reported that acini-like structures exposed to hypoxia display epithelial disorganization and delayed lumen formation. We found that hypoxia, via HIF-1α, targets signaling pathways, specifically the Erk-Bim axis, to suppress anoikis-cell death in a 3D acinar model. Here, we discuss these findings further and present additional data, indicating that hypoxia-mediated alterations in acinar architecture and anoikis-associated Erk-Bim signaling are maintained in mammary epithelial cells after reoxygenation. Taken together, these findings may offer new insight into the contribution of hypoxia-mediated signaling in the progression of early breast cancer lesions and possible treatment of hypoxic cancers.     

Characteristic cytological features of histological grade one (G1) breast carcinomas in fine needle aspirates

Objective:  To analyse the spectrum of nuclear features as well as dissociation pattern found in fine needle aspirates (FNAC) from histological grade 1 breast carcinomas and evaluate the critical cytological features of these lesions.
Material and methods:  The material consisted of FNAC smears from 494 histologically confirmed grade 1 breast carcinomas. All smears were revaluated for cell dissociation pattern, nuclear size, cell uniformity, nucleoli, nuclear margin and chromatin pattern. All features were compared with the histological subtype and cytological grading.
Results:  73.9% of the cases were cytological grade 1, 24.3% were grade 2 and 1.8% were grade 3. The majority of the cases had a cell dissociation pattern showing both a population of single carcinoma cells and cell clusters (65.9%). Practically all tumours had a granular chromatin pattern (94.7%) and a slightly irregular nuclear margin with folds and grooves (94%) irrespective of histological subtype and cytological grading. Nucleoli were mostly indistinct or small (74%), whereas 24.3% were noticeable and 1.7% abnormal. Practically all cases revealed some degree of pleomorphism with 74.3% showing mild and 22.4% a distinct pleomorphism. A small subgroup of IDC was classified as monomorphic (3.3%). Almost all tumours had nuclear sizes in the range of 2–4 × RBC (96.9%).
Conclusion:  Not all histological grade 1 carcinomas are cytological grade 1. About 25% were grade 2, and a small subpopulation reached grade 3. The typical/average findings in FNAC from grade 1 breast carcinomas were a population of both groups and single cells showing mild pleomorphism, granular chromatin, slightly irregular nuclear margin, indistinct nucleolus and nuclear size 2–4 × RBC.