Three-dimensional microanatomy of human nipple visualized by X-ray dark-field computed tomography.

PURPOSE: The three-dimensional (3D) structure of the human nipple has not been fully clarified. However, its importance has increased in recent years because it has become common practice to preoperatively explore the spread of breast cancer to the nipple with needle biopsy, ductoscopy, and/or ductal lavage for nipple-sparing mastectomy. Here, we demonstrated that X-ray dark-field computed tomography (XDFI-CT) is a powerful tool for reconstructing the 3D distribution pattern of human lactiferous ducts non-destructively, without contrast agent, and with high tissue contrast. METHODS: Nipples amputated from mastectomy specimens of 51 patients with breast cancer were visualized three-dimensionally by XDFI-CT. First, CT images and conventionally stained tissue sections were compared to demonstrate that XDFI-CT provides 3D anatomical information. Next, the number of ducts in the nipple and the number of ducts sharing an ostium near the tip of the nipple were measured from the volume set of XDFI-CT. Finally, the 3D distribution pattern of the ducts was determined. RESULTS: XDFI-CT can provide images almost equivalent to those of low-magnification light microscopy of conventional hematoxylin-eosin-stained histological sections. The mean number of ducts in all cases was 28.0. The total number of ducts sharing an ostium near the tip of the nipple was 525 of 1428. The 3D distribution patterns of the ducts were classified into three types that we defined as convergent (22%), straight (39%), or divergent (39%). CONCLUSIONS: XDFI-CT is useful for exploring the microanatomy of the human nipple and might be used for non-invasive nipple diagnosis in the future.

Microglandular adenosis associated with triple-negative breast cancer is a neoplastic lesion of triple-negative phenotype harbouring TP53 somatic mutations.

Microglandular adenosis (MGA) is a rare proliferative lesion of the breast composed of small glands lacking myoepithelial cells and lined by S100-positive, oestrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative epithelial cells. There is evidence to suggest that MGA may constitute a non-obligate precursor of triple-negative breast cancer (TNBC). We sought to define the genomic landscape of pure MGA and of MGA, atypical MGA (AMGA) and associated TNBCs, and to determine whether synchronous MGA, AMGA, and TNBCs would be clonally related. Two pure MGAs and eight cases of MGA and/or AMGA associated with in situ or invasive TNBC were collected, microdissected, and subjected to massively parallel sequencing targeting all coding regions of 236 genes recurrently mutated in breast cancer or related to DNA repair. Pure MGAs lacked clonal non-synonymous somatic mutations and displayed limited copy number alterations (CNAs); conversely, all MGAs (n = 7) and AMGAs (n = 3) associated with TNBC harboured at least one somatic non-synonymous mutation (range 3-14 and 1-10, respectively). In all cases where TNBCs were analyzed, identical TP53 mutations and similar patterns of gene CNAs were found in the MGA and/or AMGA and in the associated TNBC. In the MGA/AMGA associated with TNBC lacking TP53 mutations, somatic mutations affecting PI3K pathway-related genes (eg PTEN, PIK3CA, and INPP4B) and tyrosine kinase receptor signalling-related genes (eg ERBB3 and FGFR2) were identified. At diagnosis, MGAs associated with TNBC were found to display subclonal populations, and clonal shifts in the progression from MGA to AMGA and/or to TNBC were observed. Our results demonstrate the heterogeneity of MGAs, and that MGAs associated with TNBC, but not necessarily pure MGAs, are genetically advanced, clonal, and neoplastic lesions harbouring recurrent mutations in TP53 and/or other cancer genes, supporting the notion that a subset of MGAs and AMGAs may constitute non-obligate precursors of TNBCs.

Genetic events in the progression of adenoid cystic carcinoma of the breast to high-grade triple-negative breast cancer.

Adenoid cystic carcinoma of the breast is a rare histological type of triple-negative breast cancer with an indolent clinical behavior, often driven by the MYB-NFIB fusion gene. Here we sought to define the repertoire of somatic genetic alterations in two adenoid cystic carcinomas associated with high-grade triple-negative breast cancer. The different components of each case were subjected to copy number profiling and massively parallel sequencing targeting all exons and selected regulatory and intronic regions of 488 genes. Reverse transcription PCR and fluorescence in situ hybridization were employed to investigate the presence of the MYB-NFIB translocation. The MYB-NFIB fusion gene was detected in both adenoid cystic carcinomas and their associated high-grade triple-negative breast cancer components. Although the distinct components of both cases displayed similar patterns of gene copy number alterations, massively parallel sequencing analysis revealed intratumor genetic heterogeneity. In case 1, progression from the trabecular adenoid cystic carcinoma to the high-grade triple-negative breast cancer was found to involve clonal shifts with enrichment of mutations affecting EP300, NOTCH1, ERBB2 and FGFR1 in the high-grade triple-negative breast cancer. In case 2, a clonal KMT2C mutation was present in the cribriform adenoid cystic carcinoma, solid adenoid cystic carcinoma and high-grade triple-negative breast cancer components, whereas a mutation affecting MYB was present only in the solid and high-grade triple-negative breast cancer areas and additional three mutations targeting STAG2, KDM6A and CDK12 were restricted to the high-grade triple-negative breast cancer. In conclusion, adenoid cystic carcinomas of the breast with high-grade transformation are underpinned by the MYB-NFIB fusion gene and, akin to other forms of cancer, may be constituted by a mosaic of cancer cell clones at diagnosis. The progression from adenoid cystic carcinoma to high-grade triple-negative breast cancer of no special type may involve the selection of neoplastic clones and/or the acquisition of additional genetic alterations.

Breast lesions of uncertain malignant nature and limited metastatic potential: proposals to improve their recognition and clinical management.

Breast lesions comprise a family of heterogeneous entities with variable patterns of presentation, morphology and clinical behaviour. The majority of breast lesions are classified traditionally into benign and malignant conditions and their behaviour can, in the vast majority of cases, be predicted with a reasonable degree of accuracy. However, there remain lesions which show borderline features and lie in a grey zone between benign and malignant, as their behaviour cannot be predicted reliably. Defined pathological categorization of such lesions is challenging, and for some entities is recognized to be subjective and include a range of diagnoses, and forms of terminology, which may trigger over- or undertreatment. The rarity of these lesions makes the acquisition of clinical evidence problematic and limits the development of a sufficient evidence base to support informed decision-making by clinicians and patients. Emerging molecular evidence is providing a greater understanding of the biology of these lesions, but this may or may not be reflected in their clinical behaviour. Herein we discuss some breast lesions that are associated with uncertainty regarding classification and behaviour, and hence management. These include biologically invasive malignant lesions associated with uncertain metastatic potential, such as low-grade adenosquamous carcinoma, low-grade fibromatosis-like spindle cell carcinoma and encapsulated papillary carcinoma. Other lesions of uncertain malignant nature remain, such as mammary cylindroma, atypical microglandular adenosis, mammary pleomorphic adenoma and infiltrating epitheliosis. The concept of categories of (1) breast lesions of uncertain malignant nature and (2) breast lesions of limited metastatic potential are proposed with details of which histological entities could be included in each category, and their management implications are discussed.

Phyllodes tumours of the breast: a consensus review.

Phyllodes tumours constitute an uncommon but complex group of mammary fibroepithelial lesions. Accurate and reproducible grading of these tumours has long been challenging, owing to the need to assess multiple stratified histological parameters, which may be weighted differently by individual pathologists. Distinction of benign phyllodes tumours from cellular fibroadenomas is fraught with difficulty, due to overlapping microscopic features. Similarly, separation of the malignant phyllodes tumour from spindle cell metaplastic carcinoma and primary breast sarcoma can be problematic. Phyllodes tumours are treated by surgical excision. However, there is no consensus on the definition of an appropriate surgical margin to ensure completeness of excision and reduction of recurrence risk. Interpretive subjectivity, overlapping histological diagnostic criteria, suboptimal correlation between histological classification and clinical behaviour and the lack of robust molecular predictors of outcome make further investigation of the pathogenesis of these fascinating tumours a matter of active research. This review consolidates the current understanding of their pathobiology and clinical behaviour, and includes proposals for a rational approach to the classification and management of phyllodes tumours.

Feasibility and accuracy of molecular testing in specimens obtained with small biopsy forceps: comparison with the results of surgical specimens.

BACKGROUND: During bronchoscopy, small biopsy forceps are increasingly used for the diagnosis of peripheral pulmonary lesions. However, it is unclear whether the formalin-fixed paraffin-embedded specimens sampled with the small biopsy forceps are suitable for the determination of genotypes which become indispensable for the management decision regarding patients with non-small cell lung cancer. OBJECTIVES: The aim of this study was to evaluate the feasibility and accuracy of molecular testing in the specimens obtained with 1.5-mm small biopsy forceps. METHODS: We examined specimens in 91 patients, who were enrolled in our previous 3 studies on the usefulness of thin bronchoscopes and given a diagnosis of non-small cell lung cancer by bronchoscopy with the 1.5-mm biopsy forceps, and then underwent surgical resection. An experienced pathologist examined paraffin-embedded specimens obtained by bronchoscopic biopsy or surgical resection in a blind fashion on epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) rearrangements and KRAS mutations. RESULTS: Twenty-five (27%), 2 (2%) and 5 (5%) patients had an EGFR mutation, ALK rearrangement and KRAS mutation, respectively, based on the results in surgical specimens. EGFR, ALK and KRAS testing with bronchoscopic specimens was feasible in 82 (90%), 86 (95%) and 83 (91%) patients, respectively. If molecular testing was feasible, the accuracy of EGFR, ALK and KRAS testing with bronchoscopic specimens for the results with surgical specimens was 98, 100 and 98%, respectively. CONCLUSION: The results of molecular testing in the formalin-fixed paraffin-embedded specimens obtained with the small forceps, in which the genotype could be evaluated, correlated well with those in surgically resected specimens.

Crystal analyser-based X-ray phase contrast imaging in the dark field: implementation and evaluation using excised tissue specimens.

OBJECTIVES: We demonstrate the soft tissue discrimination capability of X-ray dark-field imaging (XDFI) using a variety of human tissue specimens. METHODS: The experimental setup for XDFI comprises an X-ray source, an asymmetrically cut Bragg-type monochromator-collimator (MC), a Laue-case angle analyser (LAA) and a CCD camera. The specimen is placed between the MC and the LAA. For the light source, we used the beamline BL14C on a 2.5-GeV storage ring in the KEK Photon Factory, Tsukuba, Japan. RESULTS: In the eye specimen, phase contrast images from XDFI were able to discriminate soft-tissue structures, such as the iris, separated by aqueous humour on both sides, which have nearly equal absorption. Superiority of XDFI in imaging soft tissue was further demonstrated with a diseased iliac artery containing atherosclerotic plaque and breast samples with benign and malignant tumours. XDFI on breast tumours discriminated between the normal and diseased terminal duct lobular unit and between invasive and in-situ cancer. CONCLUSIONS: X-ray phase, as detected by XDFI, has superior contrast over absorption for soft tissue processes such as atherosclerotic plaque and breast cancer. KEY POINTS: • X-ray dark field imaging (XDFI) can dramatically increase sensitivity of phase detection. • XDFI can provide enhanced soft tissue discrimination. • With XDFI, abnormal anatomy can be visualised with high spatial/contrast resolution.

Encapsulated papillary carcinoma, apocrine type, of the breast.

The apocrine type of encapsulated papillary carcinoma (ECP-A), of the breast is a rare neoplasm and there are only eight cases reported to date. Herein, we report the ninth case. A 68-year-old Japanese woman presented with a left breast mass. The cytoplasm of the tumour cells showed positive immunostaining for GCDFP-15. Myoepithelial cells were absent within the papillary structures and at the periphery of the lesion. The clinical course of the patient was uneventful 11 months after surgery. We postulate that EPC-A belongs to the molecular apocrine type of breast carcinoma.

Phase-contrast visualization of human tissues using superimposed wavefront imaging of diffraction-enhanced x-rays.

BACKGROUND: Phase-contrast computed tomography (CT) using high-brilliance, synchrotron-generated x-rays enable three-dimensional (3D) visualization of microanatomical structures within biological specimens, offering exceptionally high-contrast images of soft tissues. Traditional methods for phase-contrast CT; however, necessitate a gap between the subject and the x-ray camera, compromising spatial resolution due to penumbral blurring. Our newly developed technique, Superimposed Wavefront Imaging of Diffraction-enhanced x-rays (SWIDeX), leverages a Laue-case Si angle analyzer affixed to a scintillator to convert x-rays to visible light, capturing second-order differential phase contrast images and effectively eliminating the distance to the x-ray camera. This innovation achieves superior spatial resolution over conventional methods. PURPOSE: In this paper, the imaging principle and CT reconstruction algorithm based on SWIDeX are presented in detail and compared with conventional analyzer-based imaging (ABI). It also shows the physical setup of SWIDeX that provides the resolution preserving second-order differential images for reconstruction. We compare the spatial resolution and the sensitivity of SWIDeX to conventional ABI. METHODS: To demonstrate high-spatial resolution achievable by SWIDeX, the internal structures of four human tissues-ductal carcinoma in situ, normal stomach, normal pancreas, and intraductal papillary mucinous neoplasm of the pancreas-were visualized using an imaging system configured at the Photon Factory's BL14B beamline under the High Energy Accelerator Research Organization (KEK). Each tissue was thinly sliced after imaging, stained with hematoxylin and eosin (H&E) for conventional microscope-based pathology. RESULTS: A comparison of SWIDeX-CT and pathological images visually demonstrates the effectiveness of SWIDeX-CT for biological tissue imaging. SWIDeX could generate clearer 3D images than existing analyzer-based phase-contrast methods and accurately delineate tissue structures, as validated against histopathological images. CONCLUSIONS: SWIDeX can visualize important 3D structures in biological soft tissue with high spatial resolution and can be an important tool for providing information between the disparate scales of clinical and pathological imaging.

Uniqueness of ductal carcinoma in situ of the breast concurrent with papilloma: implications from a detailed topographical and histopathological study of 50 cases treated by mastectomy and wide local excision.

AIMS: To clarify the diagnostic clues of ductal carcinomas in situ (DCIS) associated with papilloma and optimal clinical management of papilloma diagnosed on core needle biopsy (CNB). METHODS AND RESULTS: A total of 50 surgically resected cases were examined histopathologically and topographically. Thirty-nine cases (78%) spread in segmental fashion. Papilloma and DCIS were intermingled closely in 44 cases (88%), occupying the same areas in varying proportions from DCIS-predominant to papilloma-predominant. The two components occupied discrete areas and collided focally in six cases (12%). Most were non-high-grade. Cribriform and solid architectures with fibrovascular stroma were frequent. The cribriform pattern was unique, consisting of fused tubules separated by fibrovascular stroma. Intraductal myoepithelial cells were present to varying degrees in 40 cases (80%). In 38 cases (76%), points were identified where papilloma and DCIS coexisted or collided within a single lumen (CC point). Forty-eight cases (96%) had either intraductal myoepithelial cells or CC points, implying that DCIS and papilloma existed in the same duct system. Radiology showed segmental abnormalities in 83% of the available cases. CONCLUSIONS: Intraductal myoepithelial cells do not always guarantee benignity. Surgical resection is recommended for papilloma in CNB when radiology shows segmental abnormalities.

Clinicopathologic and immunohistochemical features of primary ductal adenocarcinoma of lacrimal gland: five new cases and review of literature.

BACKGROUND: A primary ductal adenocarcinoma of the lacrimal gland is a rare epithelial malignant tumor, and its clinicopathological and immunohistochemical features have not been well determined. The purpose of this study was to determine the clinicopathological characteristics of lacrimal duct carcinomas and to determine their long-term prognosis. METHODS: We performed immunohistochemical studies of biological and proliferative markers of primary ductal adenocarcinomas of the lacrimal gland in five patients, and followed their long term prognosis. We also reviewed nine published cases of primary ductal adenocarcinomas of the lacrimal gland. RESULTS: All specimens were positive for the androgen receptor, and three of five specimens overexpressed the HER-2/neu protein. Nuclear immunostaining for p53 ranged from 10% to 95% and that of Ki-67 from 20% to 70% in the tumor cells. Four of five patients had distant metastases and three patients died from the disease during the 5-year follow-up. CONCLUSIONS: Our findings indicate that primary ductal adenocarcinomas of the lacrimal gland express androgen receptors and a wide range of proliferative markers. Their long-term prognosis is poor.

Transesophageal bronchoscopic ultrasound-guided fine needle aspiration for diagnosis of sarcoidosis.

BACKGROUND: Several studies have reported that specimens from mediastinal lesions located adjacent to the esophagus can be sampled using an ultrasound bronchoscope instead of an ultrasound endoscope. OBJECTIVES: The aim of this study was to evaluate the diagnostic utility of transesophageal bronchoscopic ultrasound-guided fine needle aspiration using an ultrasound bronchoscope in patients with stage I/II sarcoidosis. METHODS: Thirty-three patients suspected of having stage I/II sarcoidosis were included in this prospective study. Needle aspiration through the esophagus using an ultrasound bronchoscope was performed for hilar and/or mediastinal lymph nodes. The final diagnosis of sarcoidosis was based on clinicoradiological compatibility and pathological findings. RESULTS: A total of 62 lymph nodes with a mean shortest diameter of 13.6 mm were examined. Of the 33 patients enrolled, 29 were given a final diagnosis of sarcoidosis. Four of the residual patients had other diseases (1 lung cancer, 1 tuberculosis, 2 non-specific lymphadenitis). Transesophageal bronchoscopic ultrasound-guided fine needle aspiration showed noncaseating epithelioid cell granulomas in 25 of 29 patients (86%; 95% confidence interval 73-100) with the final diagnosis of sarcoidosis. No complications were observed. CONCLUSIONS: Transesophageal bronchoscopic ultrasound-guided fine needle aspiration is feasible, safe and accurate for the diagnosis of stage I/II sarcoidosis.

Validity of computed mean compressed fibroglandular tissue thickness and breast composition for stratification of masking risk in Japanese women.

BACKGROUND: The volumetric measurement system for mammographic breast density is a high-precision objective method for evaluating the percentage of fibroglandular tissue volume (FG%). Nonetheless, FG% does not precisely correlate with subjective visual estimation (SVE) and shows poor evaluation performance regarding masking risk in patients with comparatively thin compressed breast thickness (CBT), commonly found in Japanese women. We considered that the mean compressed fibroglandular tissue thickness (mCGT), which incorporates the CBT element into the evaluation of breast density, may better predict masking risk. METHODS: Volumetric measurements and SVEs were performed on mammograms of 108 breast cancer patients from our center. mCGT was calculated as the product of CBT and FG%. SVE was classified using the Breast Imaging-Reporting and Data System classification, 5th edition. Subsequently, the performance of mCGT, SVE, and FG% in predicting masking risk was estimated using the AUC. RESULTS: The AUC values of mCGT and SVE were 0.84 (95% confidence interval, 0.71-0.92) and 0.78 (0.66-0.86), respectively (P = 0.16). The AUC of the FG% was 0.65 (0.52-0.77), which was significantly lower than that of mCGT (P < 0.001). The sensitivity and specificity of mCGT in predicting negative detection were 89% and 71%, respectively; of SVE 83% and 61% (versus 72% and 57% with FG%), suggesting that mCGT was superior to FG% in both sensitivity and specificity, and comparable with SVE. CONCLUSIONS: Objective mCGT calculated from the volumetric measurement system will highly likely be useful in evaluating breast density and supporting visual assessment for masking risk stratification.

Epithelioid myofibroblastoma of the breast: A case report and review of the literature.

INTRODUCTION: Mammary myofibroblastoma (MFB) is a rare tumour. Its clinical and pathologic characteristics have been only sporadically described. A case of epithelioid variant of MFB is reported with the diagnostic tips, the differential diagnoses, and a discussion on the possible pathogenesis. PRESENTATION OF CASE: A 74 year-old woman presented with a painless nodule in the left breast. Core needle biopsy (CNB) revealed a tumour primarily composed of epithelioid cells. Despite epithelioid appearance of the tumour cells, ductal/lobular components were absent within the tumour. As cell lineage of the epithelioid cells could not be determined with CNB, lumpectomy was performed to obtain definitive diagnosis and, at the same time, to remove the lesion. Histologically, the tumour consisted of multiple epithelioid cell nests that were spread over fibrous stroma infiltrated with adipose tissue. Spindle cells were also present, but they were fewer than epithelioid cell clusters. Occasionally, the tumour cells showed nuclear atypia. It was difficult to determine whether this tumour was benign or malignant solely with Hematoxylin-eosin stain. However, with the aid of immunohistochemical analyses, we could make a histodiagnosis of epithelioid subtype of myofibroblastoma. DISCUSSION: The differential diagnoses of epithelioid MFB include ductal, lobular, metaplastic carcinomas and mesenchymal tumours. Comprehensive knowledge of classic and variant MFB is necessary for the correct diagnosis. CONCLUSION: Pathologic diagnosis of epithelioid variant of MFB requires careful evaluation of histology and the use of a panel of immunohistochemistry. Female phenotype of breast stroma may play a role in the pathogenesis of MFB.

Appendiceal metastasis of gastric cancer clinically masquerading acute appendicitis: possible route of metastasis.

Cancer metastasis to appendix vermiformis is rare. We here report a case of appendiceal metastasis of gastric cancer, which was incidentally discovered in the appendix resected as acute appendicitis. A 65-year-old man, who had undergone distal gastrectomy for poorly differentiated adenocarcinoma 2 years before, complained of lower abdominal pain. Physical examination and laboratory tests clinically suggested acute appendicitis. Macroscopically, the serosal surface of the resected appendix was hyperaemic and white-coated. These findings were compatible with the clinical diagnosis. However, histological examination revealed intra-mural invasion of poorly differentiated adenocarcinoma. The appendix serosal and mucosal surfaces were spared from cancer involvement. As the morphological appearance of adenocarcinoma and associated extensive lymphatic invasion was similar to those seen in the primary gastric cancer, the adenocarcinoma observed in the appendix was diagnosed as a metastasis. Possible routes of metastasis to the appendix from stomach were discussed with a brief review of relevant literature.

Crystal optics simulations for delineation of the three-dimensional cellular nuclear distribution using analyzer-based refraction-contrast computed tomography.

Refraction-contrast computed tomography (RCT) using a refractive angle analyzer of Si perfect crystal can reconstruct the three-dimensional structure of biological soft tissue with contrast comparable to that of stained two-dimensional pathological images. However, the blurring of X-ray beam by the analyzer has prevented improvement of the spatial resolution of RCT, and the currently possible observation of tissue structure at a scale of approximately 20 µm provides only limited medical information. As in pathology, to differentiate between benign and malignant forms of cancer, it is necessary to observe the distribution of the cell nucleus, which is approximately 5-10 µm in diameter. In this study, based on the X-ray dynamical diffraction theory using the Takagi-Taupin equation, which calculates the propagation of X-ray energy in crystals, an analyzer crystal optical system depicting the distribution of cell nuclei was investigated by RCT imaging simulation experiments in terms of the thickness of the Laue-case analyzer, the camera pixel size and the difference in spatial resolution between the Bragg-case and Laue-case analyzers.

The Diagnostic Utility of IDH2 R172 Immunohistochemistry in Tall Cell Carcinoma With Reversed Polarity of the Breast.

Tall cell carcinoma with reversed polarity (TCCRP) is a rare histologic type of low-grade breast cancer, consisting of tall columnar cells with reversed nuclear polarity and characterized by frequent IDH2 mutations. We herein report 3 cases of TCCRP with sequencing analyses of the IDH2 gene and immunohistochemical examination using monoclonal antibodies (11C8B1) against IDH2 R172. IDH2 R172 mutations were detected in all 3 resected tumors (R172S in 2 tumors and R172T in 1 tumor), and the presence of these mutations was confirmed by IDH2 R172 immunohistochemistry. Tumor cells of TCCRP showed strong and diffuse staining for the antibody against IDH2 R172. In 1 case, tumor tissue from 2 core needle biopsy samples collected on different days were also immunohistochemically positive for IDH2 R172. These results indicate that IDH2 R172 immunohistochemistry is suitable for the detection of TCCRP in both resection and biopsy samples. In addition, a literature review revealed that R172S and R172T account for 76% of IDH2 mutations in TCCRP, suggesting that 11C8B1, which reacts with R172S and R172T, was likely most sensitive for IDH2 -mutated TCCRP among many available antibodies for IDH2 R172. Furthermore, the combination of 2 or more antibodies against IDH2 R172 could be more effective for detecting TCCRP mutation. However, it is important to note that IDH2 R172 immunohistochemistry is not absolute, because IDH2 wild type is found in a small proportion (10%) of cases, and a few cases of IDH2 -mutated TCCRP may harbor rare subtypes of R172 that are not covered by available antibodies.

Basal-like and triple-negative breast cancers: a critical review with an emphasis on the implications for pathologists and oncologists.

Breast cancer is a heterogeneous disease encompassing a variety of entities with distinct morphological features and clinical behaviors. Although morphology is often associated with the pattern of molecular aberrations in breast cancers, it is also clear that tumors of the same histological type show remarkably different clinical behavior. This is particularly true for 'basal-like cancer', which is an entity defined using gene expression analysis. The purpose of this article was to review the current state of knowledge of basal-like breast cancers, to discuss the relationship between basal-like and triple-negative breast cancers, and to clarify practical implications of these diagnoses for pathologists and oncologists.

Topographical, morphological and immunohistochemical characteristics of carcinoma in situ of the breast involving sclerosing adenosis. Two distinct topographical patterns and histological types of carcinoma in situ.

AIM: To examine the histopathological features of 24 surgically resected carcinoma in situ (CIS) involving sclerosing adenosis (SA), with special reference to the topographical relationship between CIS and SA. METHODS AND RESULTS: In 13 (54%) lesions, CIS was entirely surrounded by SA (type A) and in 11 (46%), CIS involved SA at least focally but was not confined to the SA area (type B). The mean size of CIS in type B (30.45 mm) was significantly larger than in type A (18.00 mm). The mean size of SA in type A (39.46 mm) was significantly larger than in type B (19.54 mm). Most type A CIS were non-high-grade, and the oestrogen receptor (ER)(+)/progesterone receptor (PgR)(+)/HER2(-) immunophenotype predominated. Most type B CIS were high-grade and six (54%) were ER(-)/PgR(-). Most type A were bcl-2(+)/p53(-) in both SA and CIS areas, but two (18%) apocrine ductal CIS of type B were bcl-2(-)/p53(+) in both SA and CIS areas. Expression of ER and cyclin D1 in SA was not different from that of SA unassociated with cancer. CONCLUSIONS: Most CIS involving SA arises within SA and high-grade DCIS tends to grow beyond SA. Occasional CIS may arise outside SA and secondarily involve SA.

Dedifferentiation and progression of an intracranial solitary fibrous tumor: autopsy case of a Japanese woman with a history of radiation therapy of the head during infancy.

Solitary fibrous tumor (SFT) is usually an indolent neoplasm with a low rate of local recurrence and metastasis. Although dedifferentiation of low-grade sarcoma is well documented, the concept of dedifferentiated SFT was not recognized until recently. A case of intracranial SFT with seven recurrences within 5 years, showing progression and dedifferentiation during the course of disease, is reported here. A 51-year-old woman with a history of irradiation during infancy presented with a SFT in the right posterior fossa. Because of the close proximity to the brain stem, the tumor could not be removed completely. The tumor recurred 12, 16, and 28 months after the initial operation. With the repeated recurrences, cellularity, mitotic count, and Ki-67 (MIB-1) index increased gradually. The histology suddenly changed at the fourth recurrence, which occurred 16 months after postoperative radiation therapy for the third recurrence. The tumor revealed a fibrosarcoma-like appearance with necrosis and markedly increased mitotic activity. The tumor further recurred 50, 52, and 55 months after the initial operation with the same fibrosarcoma-like histology. The patient died of uncontrolled tumor 58 months after the initial operation. In this case radiation may have played some role in the tumorigenesis, progression, and dedifferentiation of the SFT.