We report a case of a 35-year old male patient with a tumor located in the deep dermis on his forearm. The lesion was completely excised but recurred 4 years later. The patient showed no signs of neurofibromatosis type 1. The morphology and immunophenotype of the tumor corresponded to the recently characterized group of soft tissue spindle cell lesions defined by a relatively uniform cytomorphology, patternless architecture, conspicuous stromal and perivascular hyalinization, S100 and CD34 coexpression and recurrent fusions involving RAF1, BRAF, and NTRK1/2 genes. Using a 592-gene panel and massively parallel next-generation sequencing platform, we initially detected only NF1 gene mutation in our case. However, further molecular testing with Archer fusion assay revealed a novel NCOA4-RET gene fusion, adding it to the list of multiple kinase fusions originally reported in these tumors. Although break-apart FISH showed false negative result due to the presence of intrachromosomal rearrangement, RT-PCR confirmed the fusion transcript. Knowing the exact fusion is of great clinical importance especially for patients within the aggressive subset of these neoplasms that could be treated with selective kinase inhibitors. The presented case underscores the benefits of massively parallel sequencing as the types and number of gene fusions these tumors can potentially harbor render single-gene assays such as FISH impractical, and in this particular case, also insensitive.
- Klíčová slova
- NCOA4-RET, NF1 gene mutation, S100 and CD34 positive spindle cell tumor, infantile fibrosarcoma, kinase fusions, soft tissues,
- MeSH
- antigeny CD34 genetika metabolismus MeSH
- dospělí MeSH
- hyalin metabolismus MeSH
- koaktivátory jaderných receptorů genetika metabolismus MeSH
- lidé MeSH
- mutace MeSH
- nádory měkkých tkání genetika patologie MeSH
- neurofibromin 1 genetika MeSH
- onkogenní fúze * MeSH
- proteiny S100 genetika metabolismus MeSH
- protoonkogenní proteiny c-ret genetika metabolismus MeSH
- škára metabolismus patologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antigeny CD34 MeSH
- koaktivátory jaderných receptorů MeSH
- NCOA4 protein, human MeSH Prohlížeč
- neurofibromin 1 MeSH
- NF1 protein, human MeSH Prohlížeč
- proteiny S100 MeSH
- protoonkogenní proteiny c-ret MeSH
- RET protein, human MeSH Prohlížeč
Aortic valve stenosis is characterized by inflammation and extracellular matrix remodelling. The aim of this study was to analyse the impact of mast cells on the occurrence of histopathological changes of aortic valves in patients with severe grade, non-rheumatic degenerative aortic valve stenosis. Valve specimens were obtained from 38 patients undergoing valve replacement. The role of mast cells was analysed by dividing the specimens into two groups, characterized by the presence (group A, N = 13) or absence of mast cells (group B, N = 25). There were no significant differences in clinical data between the two groups. In group A, T cells and macrophages were present in all aortic valves, as compared to a significantly lower proportion of valves with T cells and macrophages in group B. Valves in group A were less often calcified and hyaline-degenerated than valves in group B. There were no changes in fibrosis between the two groups. We found a positive correlation between the presence of mast cells and macrophages/T cells, a negative correlation between the presence of mast cells and calcification/ hyaline degeneration, and no correlation between the presence of mast cells and fibrosis. There was also a negative correlation between the presence of macrophages/T cells and calcification. The linear regression model identified only the presence of mast cells as an independent negative prediction value for calcification. In conclusion, mast cells might have a protective role against the development of calcification and hyaline degeneration in severe grade, non-rheumatic aortic valve stenosis.
- MeSH
- aortální chlopeň patologie MeSH
- aortální stenóza patologie MeSH
- dospělí MeSH
- extracelulární matrix metabolismus MeSH
- hyalin metabolismus MeSH
- kalcinóza patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- makrofágy metabolismus MeSH
- mastocyty metabolismus MeSH
- ochranné látky metabolismus MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- T-lymfocyty metabolismus MeSH
- zánět patologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- ochranné látky MeSH
We describe 23 cases of high-grade myxoinflammatory fibroblastic sarcoma (MIFS). The patients were 15 women and 8 men, with the age ranging at the time of diagnosis from 39 to 93 years (mean, 64.3 years; median, 66 years). Follow-up was available for 18 patients, of whom 9 developed metastatic disease; 7 of these died. Most tumors showed a predilection for the soft tissues of the extremities, with 14 cases involving the lower limb and 5 the upper extremity. However, in both sites, the acral parts were affected in only 1 case each. Of the 4 remaining tumors, 2 were found in axilla, 1 was found in sacral area, and 1 developed in the scar on the breast, 14 years after previous excision of a mammary carcinoma and subsequent local irradiation. The tumor size ranged from 1.3 cm to as much as 30 cm in the largest dimension with a mean size of 8.3 cm. Histologically, the tumors were characterized by occurrence of 3 types of characteristic cells, including (1) lipoblast-like cells with an ample, distended, mucin-filled cytoplasm compartmentalized by a variable number of intracytoplasmic septa, thus remotely resembling soccer balls; (2) large, polygonal, bizarre ganglion-like cells similar to those seen in the Hodgkin disease, also called Reed-Sternberg-like cells. Within an ample, deeply eosinophilic cytoplasm, there was an oval nucleus with vesicular chromatin and a large, inclusion-like nucleolus. Binucleated, multinucleated, or more pleomorphic forms of these cells were also present; (3) cells with emperipolesis of variable sizes, ranging from very inconspicuous neoplastic cells containing only one to a few engulfed cells to conspicuous large ones having many inflammatory cells, usually polymorphonuclear leukocytes admixed with various numbers of some lymphoid cells, within the cytoplasm. Quite often, we found elements that combined the histologic features of all the above 3 characteristic tumor cell types. In 2 tumors, we found an additional undifferentiated spindle cell sarcoma component, whereas in another tumor, a chondrosarcomatous moiety was evident. For comparison, we studied 10 cases of pleomorphic hyalinizing angiectatic tumor (PHAT) of soft tissues. Based on the identification of morphological changes typical for MIFS within most of the cases of PHAT, we suggest that most cases of PHAT represent examples of MIFS merely having hyaline ectatic vessels.
- Klíčová slova
- Chondrosarcoma, High-grade myxoinflammatory fibroblastic sarcoma, Pleomorphic hyalinizing angiectatic tumor, Soft tissues, Undifferentiated sarcoma,
- MeSH
- chondrosarkom metabolismus patologie MeSH
- cyklin D1 metabolismus MeSH
- dospělí MeSH
- fibrosarkom metabolismus patologie MeSH
- hyalin metabolismus MeSH
- imunohistochemie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru metabolismus patologie MeSH
- myxosarkom metabolismus patologie MeSH
- nádory měkkých tkání metabolismus patologie MeSH
- následné studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- zánět metabolismus patologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- cyklin D1 MeSH
We report 5 patients with cellular ovarian fibromas, which contained heavy depositions of hyaline globules, a remarkable and very conspicuous histologic feature of all tumors. The hyaline globules ranged in size from 1 to 25 microm. Some cells were stuffed with myriads of small hyaline globules 1 to 3 microm in size, whereas in the other cells the globules were up to 25 microm in size. The hyaline globules were stained with periodic acid-Schiff, and were mucicarmine and Alcian blue negative. These hyaline globules were present, at least in small numbers, in all 100 hematoxylin and eosin slides reviewed from all 5 cases in this series. Often the cells containing the hyaline globules showed a signet-ring appearance in the more compact cellular areas. All the tumors in our series appear to have a benign course. The patients were without signs of recurrence and without metastasis 1, 2, 3, and 6 years after the excision of the neoplasms. Follow-up in one of the patients was not available. The distinction of the ovarian fibromas with hyaline globules from the Krukenberg tumors and yolk sac tumor is discussed in the paper.
- MeSH
- diferenciální diagnóza MeSH
- fibrom metabolismus patologie MeSH
- hyalin metabolismus MeSH
- imunohistochemie MeSH
- Krukenbergův nádor patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- nádor z entodermálního sinusu patologie MeSH
- nádory vaječníků metabolismus patologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Pleomorphic hyalinizing angiectatic tumor (PHAT) of the soft tissue is a rare distinctive tumor listed as a benign neoplasm in the new World Health Organization classification. It may recur and most reported recurrent tumors retained the typical morphological appearance of PHAT; rare tumors recurred with the appearance of a sarcoma. Reported herein is an additional example of recurrent PHAT, but in contrast to the previously described cases the present tumor morphologically qualified as a sarcoma from the very beginning; it recurred as a high-grade myxofibrosarcoma. A 76-year-old woman presented with a solitary subcutaneous tumor in the axilla that was surgically removed. Seven months later, the patient experienced a local recurrence. Microscopically, the typical features of PHAT were identified in the initial lesion, namely hyalinized, fibrin-containing vessels and pleomorphic stromal cells; there were areas of hemorrhage and necrosis. Additionally, peripherally located areas of the tumor manifested highly pleomorphic cells with frequent atypical mitoses, producing a sarcomatous appearance. The mitotic index in the sarcomatous part was 1/10 high-power fields (HPF). Hyalinized, fibrin-containing vessels were absent in these sarcomatous areas, and the stroma was myxoid. The recurrent lesion was composed of large highly pleomorphic oval, round, spindled or bizarre cells with a high mitotic rate, ranging from 3/10 HPF to 7/10 HPF. The neoplastic cells were arranged haphazardly in a myxoid matrix. Hyalinized, fibrin-containing vessels typical for PHAT were absent. PHAT may be more aggressive than previously thought, and PHAT may encompass a morphological spectrum of the lesion ranging from benign to malignant.
- MeSH
- dermatofibrosarkom patologie MeSH
- fibrin metabolismus MeSH
- hyalin metabolismus MeSH
- kůže krevní zásobení metabolismus patologie MeSH
- lidé MeSH
- lokální recidiva nádoru MeSH
- nádory kůže patologie MeSH
- nekróza MeSH
- sarkom metabolismus patologie MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- Názvy látek
- fibrin MeSH
A unique and never-before-published example of clear cell renal cell carcinoma (CRCC) found among 9000 primary renal cell tumors is presented. The tumor contained such a dense concentration of glassy hyaline globules (GHG) in the cytoplasm of the neoplastic cells that it overshadowed the morphology of the neoplasm. The resulting appearance of the tumor was quite misleading and different from the conventional CRCC. The GHG were 7-30 microm in diameter. They were glassy and pale to slightly eosinophilic in color in hematoxylin-eosin. The GHG stained positively with periodic acid-Schiff and negatively with silver and Hale's colloidal iron. Immunohistochemically, they were also negative for anti Mycobacterium bovis antigen. At the ultrastructural level, the GHG were formed by an amorphous mass of stellate shape. The GHG were localized within rough endoplasmic reticulum. Molecular genetically, mutation of the distal part of exon 3 of the VHL gene causing elongation of the VHL protein was found in the tumor, thus confirming the diagnosis of CRCC.
- MeSH
- cytoplazma metabolismus ultrastruktura MeSH
- DNA nádorová analýza MeSH
- DNA primery chemie MeSH
- hyalin metabolismus ultrastruktura MeSH
- karcinom z renálních buněk diagnóza genetika metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- messenger RNA genetika metabolismus MeSH
- molekulární sekvence - údaje MeSH
- nádorové supresorové proteiny genetika metabolismus MeSH
- nádorový supresorový protein VHL MeSH
- nádory ledvin diagnóza genetika metabolismus MeSH
- nefrektomie MeSH
- posunová mutace MeSH
- RNA nádorová analýza MeSH
- sekvence aminokyselin MeSH
- sekvence nukleotidů MeSH
- sekvenční analýza RNA MeSH
- spironolakton metabolismus MeSH
- ubikvitinligasy genetika metabolismus MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- Názvy látek
- DNA nádorová MeSH
- DNA primery MeSH
- messenger RNA MeSH
- nádorové supresorové proteiny MeSH
- nádorový supresorový protein VHL MeSH
- RNA nádorová MeSH
- spironolakton MeSH
- ubikvitinligasy MeSH
- VHL protein, human MeSH Prohlížeč
Juvenile hyaline fibromatosis is a rare autosomal recessive interstitial disease characterized by nodes and tumours of skin and soft tissues as well as by gingival hyperplasia. The authors described a case of 28-year-old male based on histopathological diagnosis. The patient was admitted to the hospital thrice in his life with the diagnosis of arthrogryphosis. Last time he presented with extensive secondary impetigo in extremities and pachydermia, polymalformation syndrome, multiple subcutaneous tumours, gingival hypertrophy, contractures, osteolytic lesions and positive family history. In histology, tumoriform lesions showed a structureless hyaline matrix often with chondroosseous metaplasia and calcium salts. More or less numerous cells in the matrix had a fibroblastoid appearance with eosinophilic cytoplasm, oval nuclei and frequently pericytoplasmic halo. Electron microscopy revealed dilated cisterns of rough endoplasmic reticulum and a hypertrophied Golgi apparatus. Particles representing calcium salts according to their density were rare. Immunohistochemistry of tumour cells showed vimentin, alpha-1-antichymotrypsin and alpha-1-antitrypsin. The findings concurred with the literature in which, nevertheless, the immunohistochemical picture were not mentioned.
- MeSH
- dospělí MeSH
- fibrom metabolismus patologie MeSH
- fibromatóza dásní patologie MeSH
- hyalin metabolismus MeSH
- lidé MeSH
- nádory kůže metabolismus patologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- kazuistiky MeSH
The presence of glassy hyaline globules (GHG) in renal carcinomas has been rarely emphasized in the literature. We studied the frequency of these globules in numerous renal carcinomas, including granular cell, mixed clear cell/granular cell, papillary renal cell, and chromophobe renal cell carcinoma, as well as oncocytomas. GHG are eosinophilic bodies in the hematoxylin-eosin stained sections with a size ranging from 1 to 30 micrometer and strongly positive with the periodic acid-Schiff (PAS) histochemical stain. Ultrastructurally, they are seen as amorphous secretion inside of the cisternae of the rough endoplasmic reticulum. GHG were found in 49 of 64 cases of granular cell and mixed clear cell/granular cell renal carcinomas and in 5 of 33 papillary renal cell carcinomas. No GHG were found in 22 cases of chromophobe cell carcinomas and 26 renal oncocytomas. Our findings suggests that GHG are a characteristic feature of granular cell carcinomas, mixed clear cell/granular cell renal carcinomas, and in a small minority of papillary renal cell carcinomas. In addition, it suggests that the presence of GHG in a renal cell tumor may be of aid for excluding a diagnosis of chromophobe cell carcinoma or oncocytoma.
The presented anomaly consists of a doubled mandibular condylus in a boy aged 5.5 years. We report this case because of its rare localisation, shape, size and microscopic pattern. It represents a doubled articular process arising from the mandibular processus coronoideus. From the morphologic view the finding is very exceptional. We failed to find any similar case in the literature available. The findings of doubled articular processes (condylus bifidus) previously quoted are of different origin. In this case it was obviously disorder in the differentiation of the mandible within the period when the mandibular ramus basis was formed by the secondary cartilage.
- MeSH
- chrupavka abnormality patologie MeSH
- hyalin MeSH
- kolagen MeSH
- lidé MeSH
- mandibula abnormality patologie MeSH
- pojivová tkáň patologie MeSH
- předškolní dítě MeSH
- processus condylaris mandibulae abnormality patologie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- Názvy látek
- kolagen MeSH
We describe what we believe to be the fifth case of a degenerative condition of the brain characterized by unusual intracytoplasmic inclusions in neocortical astrocytes, and we review four previous reports of what appears to be the same condition. Whereas these previous cases were characterized by prolonged clinical mental and psychomotor retardation, our case describes a rapid onset in a previously fit and mentally able patient in whom the astrocytic inclusions showed a close association with fibrohyaline vascular degeneration and changes resembling those of Alzheimer's disease. The inclusions, which were most frequent in the second to fourth layers of the frontal, temporal, and occipital cortices but absent from subcortical regions, consisted of large, irregular hyaline bodies surrounding the nucleus and extending into the proximal parts of cell processes. Ultrastructurally they consisted of free ribosomes in a granular and filamentous matrix. They were not bound by a membrane. Lipofuscin granules were associated with them. It is suggested that the inclusions might result from a disturbance of protein metabolism in protoplasmic astrocytes, but their true significance is unknown.
- MeSH
- astrocyty patologie MeSH
- buněčná inkluze patologie MeSH
- demence patologie MeSH
- hyalin MeSH
- lidé středního věku MeSH
- lidé MeSH
- mozek krevní zásobení MeSH
- mozková kůra patologie MeSH
- nemoci mozku patologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
