Infantile myofibromatosis is a distinctive type of fibromatosis that usually develops during the immediate perinatal period. There are variants with solitary and multiple tumors. Lesions confined to the skin, soft tissue, and bone carry a good prognosis, showing spontaneous regression. The prognosis, however, is much less favorable when visceral lesions are present and the outcome may be fatal. Only recently it became obvious that there is an adult counterpart of infantile myofibromatosis, characterized by solitary lesions that have a predilection for involve the dermis and show no tendency to regression, although they have an entirely benign biological behavior. These lesions have been named cutaneous myofibroma or solitary myofibroma of adults. We have studied the clinical, histopathological and immunohistochemical characteristics of 53 examples of cutaneous adult myofibroma. In addition, 2 cases were examined ultrastructurally. The patients were mostly adults with ages ranging from 6-83 years. The lesions presented as solitary, usually painless nodules of variable duration on the skin, usually located on the extremities. Histopathologically, four patterns were identified: nodular or cellular type, multinodular or biphasic type, leiomyoma-like or fascicular type, and vascular type. A correlation between the histopathologic pattern and the lesional age was observed: vascular type of cutaneous adult myofibroma in early lesions, nodular and multinodular lesions in fully developed lesions, and leiomyoma-like or fascicular type in late lesions. Immunohistochemically, the spindle cells were desmin negative, but expressed immunoreactivity for vimentin, pan-smooth muscle actin, and alpha-smooth muscle actin. Ultrastructurally, neoplastic cells showed characteristics of undifferentiated mesenchymal cells with features of fibroblasts, myofibroblasts and pericytes. Primitive vascular formations were seen in the form of irregular clefts between adjoining cells. We conclude that cutaneous adult myofibroma is a little-known benign vascular neoplasm probably derived from myopericytes.

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Atypical fibroxanthoma is a superficial variant of pleomorphic malignant fibrous histiocytoma. Histopathologically, it is characterized by a dermal nodule composed of bizarre cells arranged in a haphazard-to-fascicular pattern. These cells are spindle or rounded, pleomorphic and with numerous atypical mitotic figures. Some cells appear polygonal with ample and foamy cytoplasm. We recently encountered two elderly patients with atypical fibroxanthoma on their face. Histopathologically, one of the lesions was composed, almost entirely, of clear cells, whereas in the other one aggregations of clear cells constituted a half of the neoplasm. Atypical multinucleated cells with a Touton-like appearance were present. In addition to clear cells, areas of more conventional atypical spindle cells arranged in fascicles were seen, supporting the diagnosis of atypical fibroxanthoma. PAS staining failed to demonstrate glycogen in neoplastic cells. Immunohistochemistry revealed that neoplastic cells expressed positivity for vimentin, muscle-specific actin, and alpha smooth muscle actin, whereas cytokeratin, S-100 protein, EMA, CEA, and desmin were negative. Ultrastructural studies showed that neoplastic cells contained abundant rough endoplasmic reticulum, mitochondria, and numerous lipid vacuoles within the cytoplasm. Clear-cell atypical fibroxanthoma is a rare variant of atypical fibroxanthoma that should be differentiated from other clear-cell neoplasms of the skin.

To identify a group of patients who might benefit from the addition of weekly paclitaxel to conventional anthracycline-containing chemotherapy as adjuvant therapy of node-positive operable breast cancer. The predictive value of PAM50 subtypes and the 11-gene proliferation score contained within the PAM50 assay were evaluated in 820 patients from the GEICAM/9906 randomized phase III trial comparing adjuvant FEC to FEC followed by weekly paclitaxel (FEC-P). Multivariable Cox regression analyses of the secondary endpoint of overall survival (OS) were performed to determine the significance of the interaction between treatment and the (1) PAM50 subtypes, (2) PAM50 proliferation score, and (3) clinical and pathological variables. Similar OS analyses were performed in 222 patients treated with weekly paclitaxel versus paclitaxel every 3 weeks in the CALGB/9342 and 9840 metastatic clinical trials. In GEICAM/9906, with a median follow up of 8.7 years, OS of the FEC-P arm was significantly superior compared to the FEC arm (unadjusted HR = 0.693, p = 0.013). A benefit from paclitaxel was only observed in the group of patients with a low PAM50 proliferation score (unadjusted HR = 0.23, p < 0.001; and interaction test, p = 0.006). No significant interactions between treatment and the PAM50 subtypes or the various clinical–pathological variables, including Ki-67 and histologic grade, were identified. Finally, similar OS results were obtained in the CALGB data set, although the interaction test did not reach statistical significance (p = 0.109). The PAM50 proliferation score identifies a subset of patients with a low proliferation status that may derive a larger benefit from weekly paclitaxel.Electronic supplementary materialThe online version of this article (doi:10.1007/s10549-013-2416-2) contains supplementary material, which is available to authorized users.

Autopsy has been one of the most important techniques for the development of modern medicine, mainly during the nineteenth century and the first half of last century. However, in the last few years, the number of autopsies performed in hospitals has dramatically decreased all over the world. This loss of interest can be attributed both to important advances in other diagnostic and therapeutic techniques and to the fear of malpractice suits. Several groups have tried to overcome this problem, developing different autopsy techniques, one of which is needle autopsy. Most authors using this technique have acknowledged that it is difficult to obtain material from certain organs and lesions, which makes its diagnostic reliability worse than that of conventional autopsy. To overcome this drawback, our team has recently developed a modification of needle autopsy, called ultrasonographic autopsy or echopsy, in which samples are obtained under ultrasonographic control. We report the results of the first 100 cases of echopsy performed in our hospital, comparing this technique with conventional autopsy performed on all the corpses. The concordance rate for the cause of death and the main pathological diagnosis between echopsy and classical autopsy was 83% in our series, which makes echopsy a feasible and reliable alternative to conventional autopsy in cases in which families refuse to give their consent for classical autopsy or in cases of infectious diseases.

Deposition of proteins leading to amyloid takes place in some neurodegenerative diseases such as Alzheimer's disease and Huntington's disease. Mutations of tau and parkin proteins produce neurofibrillary abnormalities without deposition of amyloid. Here we report that mature, parkin null, over-expressing human mutated tau (PK(-/-)/Tau(VLW)) mice have altered behaviour and dopamine neurotransmission, tau pathology in brain and amyloid deposition in brain and peripheral organs. PK(-/-)/Tau(VLW) mice have abnormal behaviour and severe drop out of dopamine neurons in the ventral midbrain, up to 70%, at 12 months and abundant phosphorylated tau positive neuritic plaques, neuro-fibrillary tangles, astrogliosis, microgliosis and plaques of murine beta-amyloid in the hippocampus. PK(-/-)/Tau(VLW) mice have organomegaly of the liver, spleen and kidneys. The electron microscopy of the liver confirmed the presence of a fibrillary protein deposits with amyloid characteristics. There is also accumulation of mouse tau in hepatocytes. These mice have lower levels of CHIP-HSP70, involved in the proteosomal degradation of tau, increased oxidative stress, measured as depletion of glutathione which, added to lack of parkin, could trigger tau accumulation and amyloidogenesis. This model is the first that demonstrates beta-amyloid deposits caused by over-expression of tau and without modification of the amyloid precursor protein, presenilins or secretases. PK(-/-)/Tau(VLW) mice provide a link between the two proteins more important for the pathogenesis of Alzheimer disease.

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The target organs in diabetes mellitus include the kidneys, the eyes and the small vessels. In these organs some specific histopathological changes have been described but there are few reports of histopathoogical changes in the lung in diabetic patients. Several reports describe abnormal pulmonary function in diabetic patients and consider these abnormalities to be due to histopahtological changes found in the pulmonary vessels. We have studied the histopathological changes in the diabetic lung comparing the findings in the autopsies of 61 diabetic and 50 non-diabetic patients. Statistically significant differences in the incidence of chronic obstructive lung disease and pulmonary haemorrhage exist. There are no differences in the incidence of fibrosis of the alveolar walls or intimal and medial thickening of small vessels, changes associated with diabetes according to the literature. We have found a specific type of nodular fibrosis not previously reported which we believe to be typical of diabetes.