Secretory carcinoma of the breast: a tumour analogous to salivary gland acinic cell carcinoma?

AIMS: Acinic cell-like breast carcinoma is a newly recognized entity, and few acinic cell-like breast carcinoma cases have been reported. All reported acinic cell-like breast carcinomas were counterparts of the solid type of acinic cell carcinoma of the salivary gland. We report here three cases of secretory breast carcinoma with acinic cell differentiation, and discuss the similarity between secretory breast carcinoma and acinic cell carcinoma of the salivary gland. METHODS AND RESULTS: The cases were histologically identical to acinic cell carcinoma of the salivary gland: papillary-cystic type in case 1, a mixture of papillary-cystic, microcystic and follicular type in case 2, and microfollicular type in case 3. Immunohistochemically, the tumour cells were positive for salivary-type amylase, lysozyme, S100 protein and alpha 1-antitrypsin, and negative or less reactive for gross cystic disease fluid protein-15 and oestrogen receptor. All three cases did not reveal metastasis or recurrence. CONCLUSIONS: These cases were typical of secretory breast carcinoma, and were clinically, histologically and immunohistochemically analogous to acinic cell carcinoma of the salivary gland. We emphasize that secretory breast carcinoma and acinic cell carcinoma of the salivary gland may be identical lesions.     

Renal cell carcinoma with leiomyomatous stroma—further immunohistochemical and molecular genetic characteristics of unusual entity

Renal cell carcinoma (RCC) with leiomyomatous stroma (RCCLS) is a recently recognized entity with indolent biological behavior. The diagnostic implication of absence/presence of VHL gene mutation, VHL hypermethylation, or/and loss of heterozygosity of chromosome 3p (LOH 3p) is widely discussed. Criteria for establishing a diagnosis of RCCLS are still lacking. Fifteen RCCLSs were retrieved from our registry. The cases were studied with consideration to the morphology, immunohistochemistry, and molecular genetics. All cases were composed of low-grade epithelial cells with clear cytoplasm arranged in nests intermingled with abundant leiomyomatous stroma. Age range of the patients was 33 to 78 years. The tumor size ranged from 1.5 to 11 cm. Six of the patients were males, and 9, females. Of the 15 tumors sent for molecular genetic testing, only 12 cases were analyzable. All cases were analyzable immunohistochemically. Of 12 of these cases, 5 showed complete absence of VHL gene mutation, VHL hypermethylation, and LOH 3p. Of these 5 cases, 3 were positive for cytokeratin 7 (CK 7). All of the 5 cases were positive for carbonic anhydrase 9, vimentin, and CD10. The remaining 7 of 12 genetically analyzable cases were found to have had VHL hypermethylation, LOH 3p, VHL gene mutation, or a combination of the former 2 characteristics. These 7 cases were positive for vimentin. Variable reactivity was found for CK 7, carbonic anhydrase 9, α-methylacyl-CoA racemase, and CD10. In 1 of these 7 cases, gains on chromosomes 7 and 17 as well as hypermethylation of VHL gene were found. This case was considered as clear cell RCC with aberrant status of chromosomes 7 and 17. Conclusions: (1) Leiomyomatous stroma is not specific for the so called RCCLS. It can be seen also in otherwise typical clear cell RCCs. (2) There are no characteristic morphological/immunohistochemical features unique for “RCCLS.” (3) Our results indicate that only tumors with the absence of the VHL gene mutation, hypermethylation, and LOH 3p can be diagnosed as RCCLS. (4) Relation of RCCs with a prominent smooth muscle stroma to the renal angiomyoadenomatous tumor/clear cell papillary (tubopapillary) RCC is not clearly evident from our study and has to be further analyzed on larger cohort of the patients.     

Clear cell papillary neoplasm of the breast with MAML2 gene rearrangement: Clear cell hidradenoma or low-grade mucoepidermoid carcinoma?

Clear cell hidradenoma (CCH) is an uncommon adnexal tumor usually arising from eccrine glands and commonly seen on the face and the upper extremities. CCH occurring in the breast is extremely rare. Herein we report a case of MAML2-rearranged CCH of breast with a papillary architecture closely mimicking intraductal papilloma, adenomyoepithelioma and low-grade mucoepidermoid carcinoma, thus representing a source of diagnostic confusion. An overview of salient histologic features and immunophenotypes to distinguish CCH and low-grade mucoepidermoid carcinoma is also integrated into the report.     

KIR alloreactivity based on the receptor–ligand model is associated with improved clinical outcomes of allogeneic hematopoietic stem cell transplantation: Result of single center prospective study

Receptors on natural killer (NK) cells, named killer immunoglobulin-like receptors (KIRs), recognize HLA class I alleles. Patients (n = 59) who received allogeneic hematopoietic stem cell transplantation (HSCT) from either a related (n = 17) or unrelated donor (n = 42) in Samsung Medical Center (Seoul, South Korea) were included. KIR mismatch was defined as incompatibility between the donor KIR and recipient KIR ligand (receptor–ligand model), and all cases were classified into the two broad haplotypes of KIR A and B. Patients with acute leukemia (n = 51, 86.4%) or myelodysplastic syndrome (n = 8, 13.6%) were included. Peripheral blood was used as the source of stem cells in all patients. Kaplan–Meier survival curves for overall survival (OS), disease-free survival (DFS), and cumulative incidence of relapse (CIR) favored recipients with a KIR-mismatched donor, although the differences were not statistically significant. In multivariate analysis, KIR mismatch was an independent prognostic indicator of a better OS (P = 0.010, HR = 0.148, 95% CI 0.034–0.639), DFS (P = 0.022, HR = 0.237, 95% CI 0.069–0.815), and CIR (P = 0.031, HR = 0.117, 95% CI 0.017–0.823). OS, DFS, and CIR did not differ significantly between the KIR A and B haplotypes.     

Hürthle cell tumours of the thyroid. A review with emphasis on mitochondrial abnormalities with clinical relevance

The molecular and enzymatic abnormalities of mitochondria in oxyphilic / oncocytic / Hürthle cells and their respective tumours are reviewed in a series of sections: ”Mitochondria, ageing, neurodegenerative diseases and cancer”, ”Mitochondrial abnormalities in Hürthle cells and Hürthle cells tumours”, ”Mitochondrion-related alterations in tumours with and without Hürthle cell/oncocytic features”, ”True and secondary oxyphilia”, and ”Bcl-2 expression, apoptosis and necrosis in Hürthle cell tumours and tumour-like lesions”. The clinicopathological and pathogenetic meaning of the data on record on these topics are discussed, with an emphasis on thyroid pathology. Received: 15 December 1999 / Accepted: 23 February     

A case of lung carcinoma with a unique biphasic feature: Implications for histogenesis of “fake mucoepidermoid carcinoma” developing in the peripheral lung

We present a case of lung carcinoma with a unique biphasic feature. The patient was a 67-year-old male smoker with idiopathic pulmonary fibrosis (IPF). A subpleural tumor in the left lower lobe, embedded in fibrotic tissue, was resected. Histologically, the tumor consisted of major and minor components of mucoepidermoid carcinoma (MEC) and surrounding conventional lepidic adenocarcinoma, respectively. Both components had the same TP53 somatic mutation (p.V157F) but not Mastermind-like 2 (MAML2) gene rearrangement. The two components may have developed from an identical origin. The tumor could be trans-differentiating from lepidic adenocarcinoma to MEC, possibly promoted by IPF-induced tissue damage. The final diagnosis was “adenosquamous carcinoma with mucoepidermoid-like features (that may originate from lepidic adenocarcinoma).” This case has implications for the potential histogenesis of peripheral lung MEC. Over time, the MEC would expand and outgrow the lepidic adenocarcinoma, making it impossible to distinguish between fake and true MEC. The present case suggests that peripheral MEC could differ from proximal MEC in its histogenesis and molecular genetics. Thus, careful examination is necessary to diagnose peripheral lung MEC, particularly in patients with interstitial lung diseases.     

Mixed acinar–endocrine carcinoma of the pancreas. A clinicopathological study and comparison with acinar-cell carcinoma

We compared the clinicopathological features of acinar-cell carcinomas (ACCs) with those of mixed acinar–endocrine carcinomas (MAECs). Specimens from 37 patients with ACC and 6 patients with MAEC were examined histologically and immunohistochemically. The mean age of ACC and MAEC patients was similar (61.3 years versus 58.4 years), but the sex ratio differed (ACC, 29 males and 8 females; MAEC, 2 males and 4 females). The size of the tumor was large in both cases (ACC, 13.8 cm in diameter; MAEC, 8.2 cm). Immunohistochemically, more than half of the tumor cells in all tumors, whether ACC or MAEC, stained for trypsin. In 20 of the 37 ACCs (54%), scattered endocrine cells (SECs) were found, which stained positively for synaptophysin (SYN) and/or chromogranin A (CGA). Interestingly, there was also a difference in the sex ratio between ACC patients without SECs (16 males and 1 female) and ACC patients with SECs (13 males and 7 females). In MAECs, the cells staining for SYN were more common than those staining for CGA and made up more than one-third of the neoplastic-cell population. In all but one case (in which the endocrine component was arranged in islet-like cell clusters), the endocrine cells were intimately mixed with trypsin-positive tumor cells. The endocrine cells only rarely expressed one of the known pancreatic or gastrointestinal hormones. Both ACCs and MAECs had a high proliferation rate and lacked p53 overexpression or progesterone and estrogen receptors. This study revealed that ACCS and MAECs share most clinicopathological features and, therefore, may form a single tumor entity, though they differ in the number of endocrine cells. The frequent identification of endocrine cells in these tumors suggests the existence of a pluripotent cell of origin that is capable of differentiating into acinar and endocrine cells.     

The largest survivorship and clinical outcomes study of the fixed bearing Stryker Triathlon Partial Knee Replacement — A multi-surgeon,single centre cohort study with a minimum of two years of follow-up

Background

The surgical management of isolated medial compartment degenerative disease of the knee causes debate. Unicompartmental arthroplasty options include fixed and mobile bearing implant designs with fixed bearing becoming increasingly popular. We present the largest cohort of a fixed bearing single radius design, Stryker Triathlon Partial Knee Replacement (PKR).

How can the study of biological processes help design new interventions for children with severe antisocial behavior?

Children with severe antisocial behavior have an increased risk of showing violently aggressive and other forms of problem behavior in adolescence and adulthood. It is well established that both biological and social factors are involved in the development of antisocial behavior. The primary aim of this paper is to discuss the evidence that specific neurobiological systems are involved in the etiology of childhood-onset antisocial behavior. These factors are responsible for the severity of the behavioral problems observed in antisocial children, but they also play a role in their persistence, because they influence children's interactions with their environment. We will discuss the possible causes of disruptions in neurobiological systems in childhood antisocial behavior and point out the implications of these findings for theory and clinical practice. We will argue that familial factors (e.g., genetic influences, early childhood adversity) are linked to negative behavioral outcomes (e.g., antisocial behavior problems) through the mediating and transactional interplay with neurobiological deficits. An investigation of neurobiological functioning in antisocial children might not only indicate which children are most likely to persist in engaging in severe antisocial behavior, but also guide the development of new interventions.     

Validation of statistical shape model based reconstruction of the proximal femur—A morphology study

Seventeen bones (sixteen cadaveric bones and one plastic bone) were used to validate a method for reconstructing a surface model of the proximal femur from 2D X-ray radiographs and a statistical shape model that was constructed from thirty training surface models. Unlike previously introduced validation studies, where surface-based distance errors were used to evaluate the reconstruction accuracy, here we propose to use errors measured based on clinically relevant morphometric parameters. For this purpose, a program was developed to robustly extract those morphometric parameters from the thirty training surface models (training population), from the seventeen surface models reconstructed from X-ray radiographs, and from the seventeen ground truth surface models obtained either by a CT-scan reconstruction method or by a laser-scan reconstruction method. A statistical analysis was then performed to classify the seventeen test bones into two categories: normal cases and outliers. This classification step depends on the measured parameters of the particular test bone. In case all parameters of a test bone were covered by the training population's parameter ranges, this bone is classified as normal bone, otherwise as outlier bone.Our experimental results showed that statistically there was no significant difference between the morphometric parameters extracted from the reconstructed surface models of the normal cases and those extracted from the reconstructed surface models of the outliers. Therefore, our statistical shape model based reconstruction technique can be used to reconstruct not only the surface model of a normal bone but also that of an outlier bone.