Diagnosis and clinical management of Exophiala dermatitidis pneumonia in a patient with anorexia nervosa: A case report.

We report a patient with anorexia nervosa without bronchiectasis and cystic fibrosis who developed acute pneumonia caused by Exophiala dermatitidis (E. dermatitidis). The black fungus found in multiple sputum cultures was determined to be E. dermatitidis using mass spectrometry and identified using genetic analysis. Although the initiation of antifungal therapy was late, the pneumonia gradually improved with long-term treatment. This case highlights the need for early diagnosis and effective long-term treatment of the fungal etiologic agent.

Glycosylated ferritin as an improved marker for post-transfusion iron overload.

Red blood cell (RBC) transfusion is an effective therapy for anemia, but repeated transfusions may cause iron overload-related damage to various organs. Iron chelation therapy, now widely available for patients who have received transfusions, is expected to reduce organ damage even in patients who received many transfusions. Therefore, determining when to start iron chelation therapy is important. In guidelines for iron chelation therapy, the serum ferritin level has been widely accepted as a practical marker for estimating iron overload. However, guidelines recommend multiple measurements of serum ferritin, because levels often fluctuate. Here, we investigated the usefulness of glycosylated ferritin as a marker of iron overload using a cohort consisted of 103 patients who had a total ferritin value over 1000 ng/mL. We found that the volume of RBCs transfused was clearly associated with the glycosylated ferritin level. We also found that acute inflammation, as represented by C-reactive protein values, was associated with increased non-glycosylated ferritin and that patients with hematopoietic diseases had higher glycosylated ferritin levels, possibly because of repeated RBC transfusions. We thus conclude that glycosylated ferritin may be an improved marker for predicting iron overload status.

Management of breast papillary lesions diagnosed in ultrasound-guided vacuum-assisted and core needle biopsies.

AIMS: To assess the outcome of breast papillary lesions diagnosed by ultrasound-guided core needle biopsy (CB) or vacuum-assisted 'mammotome' biopsy (MT), the accuracy of these diagnoses, and whether it is justified not to undertake surgical excision of non-malignant papillary lesions so diagnosed. METHODS AND RESULTS: Among 3219 (MT, 2195; CB, 1024) breast biopsies spanning 5 years, 185 (5.7%) papillary lesions [MT, 162 (88%); CB, 23 (12%)] were identified. Of these, 142 cases (77%; MT/CB, 125/17) were benign, 24 (13%, 23/1) were atypical, and 19 (10%; 14/5) were malignant. Of the 142 benign cases, 114 had imaging follow-up (FU) (FU period 2-81 months); 17 of 114 cases were excised, and four were malignant (3.5%) (FU period 4-57 months). Of the 24 atypical cases (23 had FU), 19 were excised: six were benign (32%) and 13 malignant (68%). The remaining four cases were considered to be non-malignant (FU period 7-54 months). CONCLUSIONS: Benign papillary lesions diagnosed by MT or CB might not require immediate excision, but should receive imaging FU for at least 5 years. Excision should be performed in cases showing changes in imaging features, as the possibilities of carcinoma coexisting with papilloma or carcinoma developing from papilloma cannot be excluded, as illustrated by the 4% upgrade rate at excision in this study.

Cytologic features of the endometrial adenocarcinoma: comparison of ThinPrep and BD SurePath preparations.

We compared the cytoarchitectural features used for the cytologic diagnosis of endometrial adenocarcinoma (EC) using ThinPrep® (TPS = ThinPrep Sample) and BD SurePath™ (SPS = SurePath Sample) preparations. In 20 patients, a direct endometrial sample using the Uterobrush was obtained. Nineteen cases of EA and one case of carcinosarcoma were studied. TPS and SPS were performed according to the manufacturer's recommendations. Moreover, after the TPS preparation, the residual material was also used to prepare an SPS sample (TP-SPS = ThinPrep-Surepath sample). The following points were investigated in both preparations: (1) number of cell clumps; SPS had a significantly higher (20.9) than TPS (1.7) and TP-SPS (10.3); (2) long axis of clumps; SPS had a significantly higher (215.4) than TPS (146.0); (3) rate of cell clumps with longer axes than 200 µm; SPS had a significantly higher (36.7) than TPS (15.2) and TP-SPS (24.2). TP-SPS showed higher values than TPS; (4) nuclear area; TPS had a significant higher (61.2) than SPS (40.8) and TP-SPS (38.6); (5) degree of overlapping nuclei; SPS (3.4) had a significantly higher number of overlapping nuclei than TPS (0.7) and TP-SPS (2.1); (6) nuclear chromatin pattern; no significant differences for the nuclear chromatin pattern were found in the three different methods. The poor performance of TPS versus SPS and TP-SPS was explained with the heavy blood contamination of the samples, and the absence of adhesive coating in the slides is used for TPS. Further investigation of technical differences in liquid-based cytology methodologies is needed.

Transient reduction and activation of circulating dendritic cells in patients with acute myocardial infarction.

BACKGROUND: Dendritic cells (DCs) are highly potent professional antigen-presenting cells that play a central role in initiating the primary immune response. Accumulating evidence suggests that immune-mediated inflammation plays an important role in the pathophysiology of AMI, but the mechanism that triggers such immune responses is unknown. METHODS: Using multi-color flow-cytometry, we determined the numbers of circulating myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) in patients with AMI (n = 26) or stable angina pectoris (SAP) (n = 19), and in age-matched control subjects (n = 19). The DC activation markers CD40 and CD83 were also measured. RESULTS: On admission, circulating mDC and pDC counts were significantly lower in AMI patients compared to control subjects and SAP patients (mDC, P < 0.01; pDC, P < 0.05). The activation markers of mDCs in AMI patients were significantly higher and returned to the levels of control subjects or SAP patients 3 days after AMI (mDC, P < 0.05; pDC, P < 0.05). Reductions of circulating mDC and pDC numbers were restored 7 days after the onset of AMI. Furthermore, we found that the recovery of the circulating DC numbers 14 days after AMI was correlated with the alterations of creatine kinase-MB (CK-MB) (mDC, r = 0.48, P < 0.05; pDC, r=0.52, P < 0.01) and brain natriuretic peptide (BNP) (mDC, r = 0.53, P < 0.01; pDC, r = 0.51, P < 0.01). CONCLUSION: Our findings suggest that the transient reduction and activation of circulating DCs may play important roles in the pathophysiology of myocardial injury after AMI.

Evaluation of inadequate, indeterminate, false-negative and false-positive cases in cytological examination for breast cancer according to histological type.

BACKGROUND: We previously investigated the current status of breast cytology cancer screening at seven institutes in our area of southern Fukuoka Prefecture, and found some differences in diagnostic accuracy among the institutions. In the present study, we evaluated the cases involved and noted possible reasons for their original cytological classification as inadequate, indeterminate, false-negative and false-positive according to histological type. METHODS: We evaluated the histological findings in 5693 individuals who underwent cytological examination for breast cancer (including inadequate, indeterminate, false-negative and false-positive cases), to determine the most common histological types and/or features in these settings and the usefulness/limitations of cytological examination for the diagnosis of breast cancer. RESULTS: Among 1152 cytologically inadequate cases, histology revealed that 75/173 (43.6%) cases were benign, including mastopathy (fibrocystic disease) in 38.6%, fibroadenoma in 24.0% and papilloma in 5.3%. Ninety-five of 173 (54.9%) cases were histologically malignant, with scirrhous growing type, invasive ductal carcinoma (SIDC) being significantly more frequent (49.5%) than papillotubular growing type (Papi-tub) (P < 0.0001), solid-tubular growing type (P = 0.0001) and ductal carcinoma in situ (DCIS) (P = 0.0001). Among 458 indeterminate cases, 54/139 (38.8%) were histologically benign (mastopathy, 30.0%; fibroadenoma, 27.8%; papilloma, 26.0%) and 73/139 (52.5%) were malignant, with SIDC being the most frequent malignant tumor (37.0%). Among 52 false-negative cases, SIDC was significantly more frequent (42.3%) than DCIS (P = 0.0049) and Papi-tub (P = 0.001). There were three false-positive cases, with one each of fibroadenoma, epidermal cyst and papilloma. CONCLUSIONS: The inadequate, indeterminate, false-negative and false-positive cases showed similar histological types, notably SIDC for malignant tumors, and mastopathy, fibroadenoma and papilloma for benign cases. We need to pay particular attention to the collection and assessment of aspirates for these histological types of breast disease. In particular, several inadequate, indeterminate and false-negative cases with samples collected by aspiration were diagnosed as SIDC. These findings should encourage the use of needle biopsy rather than aspiration when this histological type is identified on imaging. Namely, good communication between clinicians and pathological staff, and triple assessment (i.e., clinical, pathological and radiological assessment), are important for accurate diagnosis of aspiration samples. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7349809170055423.

Immunohistochemical study of metaplastic carcinoma and central acellular carcinoma of the breast: central acellular carcinoma is related to metaplastic carcinoma.

Metaplastic breast cancers (MBCs) [spindle cell carcinoma (SpCC), squamous cell carcinoma (SCC), and matrix-producing carcinoma (MPC)] and invasive carcinomas with central acellular zones (CACs) were analyzed with respect to biological potential by immunohistochemical analyses. Specimens from 40 patients [20 with MBCs (7 with SCC, 6 with SpCC, 5 with MPC, and 2 with mixed type)] and 20 with CACs were analyzed using antibodies to cytokeratin (CK) 8, 5/6, 14, AE1/AE3, 34αE12, involucrin, c-kit, vimentin (VIM), alpha-smooth muscle actin, p63, epidermal growth factor receptor, epithelial cell adhesion molecule, and estrogen receptor (ER)/progesterone receptor (PR)/HER2. Expression of CK5/6, 34ßE12, VIM, nuclear p63, and cytoplasmic p63 was significantly higher with MBCs than CACs (38%/13%, 70%/43%, 85%/33%, 68%/40%, and 48%/18%, respectively). Other markers were expressed at various levels in these tumors, but the difference between them was not significant. Eighteen MBC and 8 CAC cases were triple (ER/PR/HER2) negative; 17 MBCs and 7 CACs were basal-like tumors. Several differences were seen in MBCs and CACs, but they were heterogeneous, differentiating multipotentially into mesenchymal, myoepithelial, basal-like phenotypes with "stem cell-like" features. Thus, CACs are related to MBCs by immunohistochemical analyses as well as according to morphological findings.

Comparison of the accuracy of breast cytological diagnosis at seven institutions in southern Fukuoka Prefecture, Japan.

OBJECTIVE: Cytological examination is inexpensive and relatively simple to carry out and deserves utilization in breast cancer screening. We investigated the status of cytological diagnosis at seven facilities in southern Fukuoka Prefecture, Japan. METHODS: We collected data on the criteria for cytological judgments and status of breast cytological diagnosis at seven different facilities in this region. RESULTS: Among 5693 individuals who underwent breast cytological examination, analyses were conducted on 1250 individuals (22.0%) in whom cytological diagnoses were confirmed by histological diagnoses. Among these patients, cytological diagnosis had an absolute sensitivity of 71.9%, a specificity of 76.0%, a false-negative value of 6.7% and a false-positive value of 0.08%. At three facilities with relatively large numbers of cases (>300), excluding a facility for specialized breast disease, similar trends of high complete sensitivity (94.3, 95.6 and 97.1%, respectively) and low absolute sensitivity (60.4, 74.8 and 57.2%, respectively) were found. No false-negative or false-positive cases were seen in individual facilities with relatively low numbers of cases (<150). CONCLUSIONS: The accuracy of cytological diagnosis at the facilities we surveyed was relatively high compared with the goals of assessment of diagnostic accuracy. However, the performance was dependent on the facility type, i.e. number of cases, staff involved and whether it was specialized or not, making the diagnosis specific for this region. We recommend that management of the accuracy of cytological diagnosis be undertaken jointly by multiple facilities to establish systems in Japan that lead to more useful diagnostic tools.

Cytological features of myxomatous fibroadenoma of the breast.

Fibroadenoma (FA) is a benign tumor that must be differentiated from carcinomas. FAs often exhibit myxedematous changes (myxomatous FA, M-FA). We previously reported on the clinical significance of M-FA. M-FA and (mucinous) carcinoma share clinical findings, rapid growth and a relatively large size, a high-depth/width (D/W) ratio, a relatively round shape, and posterior echo enhancement with internal hyperechogenicity on ultrasonography (US). Next, a biopsy is required for differential diagnosis. In this study, we evaluated the diagnostic significance of the cytological findings of M-FA with US findings. Among 13 FAs that were diagnosed by cytology, we compared (i) a group of six mucinous carcinomas with acellular mucin and a D/W ratio ≥ 0.7 (a suspicious factor for malignancy) with a group with a D/W ratio of <0.7, and (ii) the frequency of metachromasia on Giemsa stain between M-FAs and non-M-FAs among eight FA cases confirmed by histology. (i) FA lesions (7 of 13) showed metachromasia with Giemsa staining significantly more frequently than did mucinous carcinoma (0/6) (Fisher's exact test, P < 0.044). FA lesions with a D/W ratio ≥ 0.7 (6/7) showed metachromasia significantly more frequently than did FA with a D/W ratio <0.7 (1/6) (Fisher's exact test, P < 0.029). Among eight FA cases confirmed by histology, M-FA cases (6/6) demonstrated metachromasia significantly more frequently than non-M-FA cases (0/2) (P < 0.036). M-FA cytologically exhibits marked metachromasia on Giemsa staining. Combining cytological examination and understanding the clinical features of M-FA may allow us to choose cytological examination as a first-line diagnostic method for tumor-forming lesions.

"High-grade" central acellular carcinoma and matrix-producing carcinoma of the breast: correlation between ultrasonographic findings and pathological features.

High-grade carcinoma with a large central acellular zone (central acellular carcinoma, CAC) and matrixproducing carcinoma (MPC) are aggressive tumors that both have a central myxomatous acellular zone. Their characteristic morphology may be useful in diagnostic imaging. Ultrasonographic findings based on the Breast Imaging Recording and Data System (BI-RADS) and detailed histological features were evaluated in 11 cases of CAC and 2 cases of MPC to characterize their features. Safranin-O staining was undertaken for the evaluation of central acellular zones in these tumors. Overall, ultrasonography demonstrated heterogeneous hyperechoic lesions in the center of the hypoechoic mass. Posterior echo enhancement was observed in all but 1 case. One case was classified as malignant and the others as "borderline." Histologically, cancer tissue was located in the periphery of the tumor with a ring-like structure and fewer cellular central areas comprising hyaline cartilage myxoid material such as those stained by safranin-O. The present study showed that the pathological findings of CACs and MPCs accurately reflect the ultrasonographic findings. Tumors that showed hyperechoic areas in the center of the hypoechoic mass, with posterior echo enhancement indicating acellular zones composed by myxochondroid material, and that were also relatively round on ultrasonography may be benign, but evaluation is required to exclude CAC and MPC.

Myxomatous fibroadenoma of the breast: correlation with clinicopathologic and radiologic features.

Fibroadenoma is a frequently encountered benign tumor that must be differentiated from carcinoma. Fibroadenomas often exhibit myxedematous changes (myxomatous fibroadenoma). We focused on myxomatous fibroadenomas and evaluated their diagnostic imaging and clinicopathologic findings. We examined the (1) clinicopathologic findings of myxomatous fibroadenomas out of 113 fibroadenomas among 592 needle biopsy cases and (2) clinical findings of 27 patients with fibroadenoma who underwent surgical resection. One hundred thirteen (19%) of 592 cases were fibroadenoma, of which 45 cases (40%) were myxomatous fibroadenoma. Based on ultrasonography findings, the depth to width ratio was significantly higher in the myxomatous fibroadenoma group (0.79 ± 0.26) compared with the non-myxomatous fibroadenoma group (0.64 ± 0.26) (P < .01). Forty-two patients were subjected to needle biopsy to differentiate fibroadenoma from carcinomas based on ultrasonography and clinical findings, of which 13 cases (31%) were myxomatous fibroadenoma. These lesions showed a relatively round shape and increased posterior echo enhancement with internal hyperechogenicity on ultrasonography. Among 17 resected cases suspected of malignancy that showed rapid growth and/or size greater than 3 cm, 16 cases were myxomatous fibroadenoma. Tumors showing rapid growth and a relatively large size, a high depth to width ratio, a relatively round shape, and posterior echo enhancement with internal hyperechogenicity on ultrasonography require differentiation from (mucinous) carcinoma but are histologically more likely to be myxomatous fibroadenoma. Understanding the histologic features and combining the ultrasonography findings of myxomatous fibroadenomas may permit reduction in the number of unnecessary needle biopsies for tumor-forming lesions.

Recurrence of invasive micropapillary carcinoma of the breast with different ultrasound features according to lesion site: case report.

Invasive micropapillary carcinoma (IMPC) of the breast is a distinct variant of breast cancer. Extensive lymphatic penetration, lymph node metastasis, and local recurrence are seen at a relatively high frequency. On ultrasound (US) findings, IMPC has been reported to be an irregular or lobulated mass with hypoechoic internal areas, but as yet there is no consensus regarding typical findings. A 52-year-old female noticed a mass less than 3 cm in diameter in her left upper breast. US findings indicated an irregularly shaped, hypoechoic tumor with indistinct margins. The diagnosis according to fine-needle aspiration cytology was invasive ductal carcinoma. She underwent lymph node dissection with mastectomy of the left breast. Histological examination revealed mixed-type IMPC. Three years and three months after surgery, IMPC recurred under the skin of the surgical scar. US findings indicated a hyperechoic tumor in this region. Eight months after further surgery, a tumor in the anterior chest wall was observed. US findings indicated an oval hypoechoic tumor with posterior acoustic enhancement. US findings differed between primary and recurrent IMPC because of differences in the occupancy and distribution of IMPC. We describe here a comparison between US and histological findings, as well as differences in IMPC between primary, secondary and tertiary sites.

Characteristic morphology of invasive micropapillary carcinoma of the breast: an immunohistochemical analysis.

OBJECTIVE: Invasive micropapillary carcinoma of the breast is a distinct variant of breast cancer. In the present study, we analyzed potential immunophenotypic changes in invasive micropapillary carcinoma. METHODS: Specimens from 15 patients with invasive micropapillary carcinoma were analyzed using clinicopathological and immunohistochemical methods. We also examined the relationship between clinicopathological factors using the Ki-67 labeling index. RESULTS: Immunohistochemical staining for cytoplasmic p63 expression was seen in four (27%) tumors, and p63 nuclear expression was also observed in four (27%) tumors. Involucrin and 34betaE12 were expressed in the invasive micropapillary carcinoma component of nine (60%) and four (27%) tumors, respectively. Cytokeratin 5/6 was expressed in three (20%) tumors and cytokeratin 14 staining was negative in all tumors. In one tumor (case 3), vimentin, epithelial membrane antigen and cytokeratin 8/18 were co-expressed. Four tumors (27%) were negative for the estrogen receptor/progesterone receptor/HER2. However, 11 out of 15 (73%) tumors were positive for the estrogen receptor. The Ki-67 labeling index was significantly higher in cases with p63 tumor expression than in those without (P < 0.0001), and also higher in cases with lymph node metastasis than in cases without (P = 0.0029). CONCLUSIONS: Nuclear expression of p63, involucrin and 34betaE12 were detected indicating squamous differentiation. Cytoplasmic p63 expression was also identified. The fact that the Ki-67 labeling index was significantly higher in such cases may have been associated with the aggressive behavior of these tumors. Our findings suggest that the characteristic morphology of invasive micropapillary carcinomas may be due to immunophenotypical and oncogenic changes.

Development of a novel catalytic membrane reactor for heterogeneous catalysis in supercritical CO2.

A novel type of high-pressure membrane reactor has been developed for hydrogenation in supercritical carbon dioxide (scCO(2)). The main objectives of the design of the reactor are the separate feeding of hydrogen and substrate in scCO(2) for safe reactions in a continuous flow process, and to reduce the reaction time. By using this new reactor, hydrogenation of cinnamaldehyde into hydrocinnamaldehyde has been successfully carried out with 100% selectivity at 50 degrees C in 10 MPa (H(2): 1 MPa, CO(2): 9 MPa) with a flow rate of substrate ranging from 0.05 to 1.0 mL/min.

Clinicocytopathology of breast cancers with a ring-like appearance on ultrasonography and/or magnetic resonance imaging.

On breast cancer imaging some cancers have an anechoic or high-echoic zone in the tumor on ultrasonography and ring-shaped enhancement on contrast-enhanced magnetic resonance imaging (MRI) with high intensity in the central area of the tumor on T2-weighted imaging, necessitating their differentiation from benign disease. Thus, nine breast cancers with a ring-like appearance on imaging were analyzed on cytopathology. Histologically the cancer cells of these lesions showing a ring-like appearance were located in the periphery of the tumor, with a central hypocellular zone. Five such lesions with a thick, doughnut-like appearance were identified as cancers with acellular zones (CAC), and four lesions with a thinner, rim-like appearance as matrix-producing carcinomas (MPC). The percentage ratio of the cancer-zone width to the tumor diameter was 26.4 +/- 7.8 and 8.0 +/- 3.2 (mean +/- SD), respectively (P= 0.003). Cytologically, highly atypical, naked-nucleus cells were observed in eight of the nine cancers. In two MPC and three CAC, cartilage matrix and amorphous material, respectively, were observed in the background. In summary, the present series of breast cancers having a ring appearance on imaging did not have uniform cytopathological features. They were classified as MPC or CAC, and cytology was useful in their diagnosis and differentiation in some cases.

Highly efficient chemoselective N-acylation with water microreaction system in the absence of catalyst.

A high-speed, highly efficient chemoselective N-acylation by anhydride was achieved in the absence of catalyst for exothermic (DeltaH>0) and endothermic (DeltaH<0) acylation of various amines and anilines with the microreaction system of ambient water (micro-onH2O) and subcritical water (micro-subH2O), where the desired N-acylated products are chemoselectively obtained with high yield(s) and excellent selectivity (>95%).

Fine-needle aspiration cytology of basal cell adenoma of the parotid gland: characteristic cytological features and diagnostic pitfalls.

We retrospectively studied the cytological features of aspiration cytology in 12 cases of basal cell adenoma (BCA) and 5 cases mistakenly diagnosed as BCA. On macroscopic findings, the 12 cases of BCA included 7 cases of solid type and 5 cases of cystic type. The characteristic cytological features of solid type BCA were three-dimensional clusters in 71%, sharp-angle small clusters in 86%, basement membrane- like material in 71%, and cell crush in 86%. In contrast, 3 of the 5 cystic type BCA cases showed inadequate cellular components or no basaloid tumor cells, and the cytological diagnosis of BCA could not be determined. In the 5 cases misdiagnosed as BCA, there were 2 cases of pleomorphic adenoma, 2 cases of benign lymphoepithelial cyst, and 1 case of basal cell adenocarcinoma. Accurate differential cytological diagnosis of BCA is relatively easy to determine the solid type BCA, but is more difficult for cystic type BCA.

Tumor growth suppression in pancreatic cancer by a putative metastasis suppressor gene Cap43/NDRG1/Drg-1 through modulation of angiogenesis.

Cap43 has been identified as a nickel- and calcium-induced gene, and is also known as N-myc downstream-regulated gene 1 (NDRG1), Drg-1 and rit42. It is also reported that overexpression of Cap43 suppresses metastasis of some malignancies, but its precise role remains unclear. In this study, we asked how Cap43 could modulate the tumor growth of pancreatic cancer. Stable Cap43 cDNA transfectants of pancreatic cancer cells with Cap43 overexpression showed similar growth rates in culture as their control counterparts with low Cap43 protein level. By contrast, Cap43 overexpression showed a marked decrease in tumor growth rates in vivo. Moreover, a marked reduction in tumor-induced angiogenesis was observed. Gelatinolytic activity by matrix metalloproteinase-9 and invasive ability in Matrigel invasion activity were markedly decreased in pancreatic cancer cell lines with high Cap43 expression. Cellular expression of matrix metalloproteinase-9 and two major angiogenic factors, vascular endothelial growth factor and interleukin-8, were also significantly decreased in cell lines with Cap43 overexpression as compared with their parental counterparts. Immunohistochemical analysis of specimens from 65 patients with pancreatic ductal adenocarcinoma showed a significant association between Cap43 expression and tumor microvascular density (P = 0.0001) as well as depth of invasion (P = 0.0003), histopathologic grading (P = 0.0244), and overall survival rates for patients with pancreatic cancer (P = 0.0062). Thus, Cap43 could play a key role in the angiogenic on- or off-switch of tumor stroma in pancreatic ductal adenocarcinoma.

Image analysis of irregularity of cluster shape in cytological diagnosis of breast tumors: cluster analysis with 2D-fractal dimension.

To establish diagnostic criteria using comparison of cell cluster shapes, between benign and malignant tumors, breast tumors demonstrating weak cellular atypia in low grade invasive ductal carcinoma (IDC) were compared. Fine-needle aspiration (FNA) specimens of breast tumors were obtained from 37 patients. Among these, 16 were histologically diagnosed as IDC low-grade and the other 21 as benign fibroadenoma (FA). For evaluation, we examined 740 clusters from these 37 FNA specimens. Nine image morphometric parameters were studied, including the cluster area, circumference, maximal length, maximal breadth, ratio of length to breadth, cluster roundness, cluster size, and the edge and distribution image fractal dimensions for cluster analysis. We evaluated the irregularity in cell cluster shape using fractal dimension analysis, and determined the correlation to cluster size. The irregularity in the IDC cluster shape was higher than that in the FA cluster shape. However, six cases (28.5%) of 21 FA clusters showed high fractal dimensions similar to those for IDC. The clusters were classified by cluster analysis into three types: IDC clusters, FA with irregular cluster shape, and FA with no irregular clusters. The average cell cluster area of the FA with irregular shape was found to be about three times larger than that of IDC clusters. When the differential diagnosis between IDC and FA is difficult, it is important to focus on irregularities in the shape and on overall size of the cell clusters. For accurate diagnosis, the cell cluster shape is as important as the individual cellular atypia.