Mucoepidermoid carcinoma associated with osteosarcoma in a true malignant mixed tumor of the submandibular region

True malignant mixed tumor, also known as carcinosarcoma, is a rare tumor of the salivary gland composed of both malignant epithelial and malignant mesenchymal elements. Frequently carcinosarcoma arises in the background of a preexisting pleomorphic adenoma; however, if no evidence of benign mixed tumor is present, the lesion is known as carcinosarcoma "de novo." We reported the first case of true malignant mixed tumor of the submandibular gland composed of high grade mucoepidermoid carcinoma associated with osteosarcoma. Case Presentation. A 69-year-old Caucasian male came to our department complaining of the appearance of an asymptomatic left submandibular neoformation progressively increasing in size over 3 months. We opted for surgical treatment. Histological examination confirmed the diagnosis of carcinosarcoma with the coexistence of high grade mucoepidermoid carcinoma and osteosarcoma. Conclusion. To the best of our knowledge, in the true malignant mixed tumor of the submandibular gland, mucoepidermoid carcinoma associated with osteosarcoma has never been previously reported

Liver: Intrahepatic cholangiocarcinoma

Review on Liver: Intrahepatic cholangiocarcinoma, with data on clinics, and the genes involved

Stepwise addition of genetic changes correlated with histological change from “well-differentiated” to “sarcomatoid” phenotypes: a case report

BACKGROUND: Sarcomatoid cancer is defined by the World Health Organization as a category of non-small cell lung cancers with sarcoma or sarcoma-like differentiation. They are characterized by poor prognosis and resistance to conventional chemotherapy. However, the mutational profile of sarcomatoid cancer remains yet to be elucidated. Sarcomatoid cancers are usually biphasic tumors composed of carcinomatous and sarcomatous components, but the evolutional development of sarcomatoid cancer is controversial. CASE PRESENTATION: We present an illustrative case of sarcomatoid cancer composed of three different histological areas. Targeted sequencing of 53 lung cancer-related genes was performed in each component and their phenotypic changes were correlated with stepwise addition of genetic changes. CONCLUSION: Sarcomatous change of carcinoma occurs in the case of sarcomatoid cancer, and phenotypic changes to sarcomatoid cancer are associated with the addition of mutation patterns and derived from poorly differentiation tumor. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-017-3059-1) contains supplementary material, which is available to authorized users

Preservation of Truncal Genomic Alterations in Clear Cell and Papillary Renal Cell Carcinomas with Sarcomatoid Features: An Intra- and Intertumoral, Multifocal Fluorescence in Situ Hybridization Analysis Reveals Limited Genetic Heterogeneity

Understanding tumor genomic heterogeneity may offer vital information in an age of targeted therapy for renal cell carcinoma. We sought to investigate hallmark truncal chromosomal alterations between conventional, sarcomatoid, and matched metastatic tumor foci in clear cell and papillary renal cell carcinomas. A retrospective review identified 58 cases including clear cell (CCRCC) and papillary renal cell carcinomas (PRCC). All cases contained sarcomatoid transformation. Additionally, 10 of 58 patients had matched metastatic disease available for analysis. Three separate foci of conventional and sarcomatoid morphologies were analyzed in each tumor using dual color interphase fluorescence in situ hybridization. In the CCRCC cohort, hallmark chromosome 3p deletion was identified in 71% of cases (37/52). Complete concordance of chromosomal status between intratumoral foci in sarcomatoid and conventional foci was 89% and 86%, respectively. Overall chromosome 3p status between matched conventional and sarcomatoid morphologies was identified in 98% of cases (51/52). Hallmark 3p deletion was present in 91% of CCRCC metastatic samples (10/11) and was concordant with the matched primary CCRCC tumor in 91% (10/11). In the PRCC cohort, trisomy 7 and 17 was identified in all six cases (6/6). Complete concordance between intratumoral foci of trisomy 7 and 17 was 83% (5/6). Trisomy 7 and 17 were identified in all metastatic PRCC samples with 100% concordance with the matched primary tumor. These data show the relative preservation of truncal chromosomal abnormalities between conventional and sarcomatoid morphologic as well as matched metastatic settings

Giant elephantiasis neuromatosa in the setting of neurofibromatosis type 1: A case report

Elephantiasis neuromatosa (EN) can arise from a plexiform neurofibroma of the superficial and deep nerves developing from a hyperproliferation of the perineural connective tissue infiltrating adjacent fat and muscles. To date, the clinical association between EN and neurofibromatosis type 1 (NF1) has been poorly defined, particularly with regard to the role of lymphatic alterations and the consequent lymphedema. The present study reports the clinical and biomolecular features of EN in a NF1 patient with the clear clinical diagnostic criteria of multiple caf\ue8-au-lait macules, neurofibromas, EN, a positive family history and a novel NF1 germline c.1541_1542del mutation. Lymphoscintigraphy (LS) highlighted marked dermal backflow in the affected limb, hypertrophy of the ipsilateral inguinal and external iliac lymph nodes, and a bilateral lower limb lymph flow delay. These data support the hypothesis that an extensive hyperproliferative process involving perineural connective, limb soft tissues, bones and the lymphatic system can be responsible for EN in NF1 patients, on the basis of adipocyte metaplasia triggered by lymphostasis and lymphedema, and bone overgrowth and gigantism caused by chronic hyperemia. LS and magnetic resonance imaging can be efficacious tools in the diagnosis and clinical characterization of the early onset of the disease

Pediatric Meningosarcoma: Clinical Evolution and Genetic Instability

This report presents a female diagnosed with a frontoparietal interhemispheric meningosarcoma who, parallel to the clinical worsening, revealed an increase in the genetic instability (in bleomycin cultures) and the complexity of the karyotypes, with the acquisition of a clonal deletion of 17p13 (the locus for the TP53 tumor suppressor gene). The genetic findings of this patient suggest that the increased genetic instability could contribute to tumor progression as well as to treatment resistance, possibly in the background of the clonal deletion of TP53

Clinical actionability of comprehensive genomic profiling for management of rare or refractory cancers

Background. The frequency with which targeted tumor sequencing results will lead to implemented change in care is unclear. Prospective assessment of the feasibility and limitations of using genomic sequencing is critically important. Methods. A prospective clinical study was conducted on 100 patients with diverse-histology, rare, or poor-prognosis cancers to evaluate the clinical actionability of a Clinical Laboratory Improvement Amendments (CLIA)-certified, comprehensive genomic profiling assay (FoundationOne), using formalin-fixed, paraffin-embedded tumors. The primary objectives were to assess utility, feasibility, and limitations of genomic sequencing for genomically guided therapy or other clinical purpose in the setting of a multidisciplinary molecular tumor board. Results. Of the tumors from the 92 patients with sufficient tissue, 88 (96%) had at least one genomic alteration (average 3.6, range 0–10). Commonly altered pathways included p53 (46%), RAS/RAF/MAPK (rat sarcoma; rapidly accelerated fibrosarcoma; mitogen-activated protein kinase) (45%), receptor tyrosine kinases/ligand (44%), PI3K/AKT/mTOR (phosphatidylinositol-4,5-bisphosphate 3-kinase; protein kinase B; mammalian target of rapamycin) (35%), transcription factors/regulators (31%), and cell cycle regulators (30%). Many low frequency but potentially actionable alterations were identified in diverse histologies. Use of comprehensive profiling led to implementable clinical action in 35% of tumors with genomic alterations, including genomically guided therapy, diagnostic modification, and trigger for germline genetic testing. Conclusion. Use of targeted next-generation sequencing in the setting of an institutional molecular tumor board led to implementable clinical action in more than one third of patients with rare and poor-prognosis cancers. Major barriers to implementation of genomically guided therapy were clinical status of the patient and drug access. Early and serial sequencing in the clinical course and expanded access to genomically guided early-phase clinical trials and targeted agents may increase actionability. Implications for Practice: Identification of key factors that facilitate use of genomic tumor testing results and implementation of genomically guided therapy may lead to enhanced benefit for patients with rare or difficult to treat cancers. Clinical use of a targeted next-generation sequencing assay in the setting of an institutional molecular tumor board led to implementable clinical action in over one third of patients with rare and poor prognosis cancers. The major barriers to implementation of genomically guided therapy were clinical status of the patient and drug access both on trial and off label. Approaches to increase actionability include early and serial sequencing in the clinical course and expanded access to genomically guided early phase clinical trials and targeted agents

Type III pleuropulmonary blastoma in a 7-month-old female baby with impending respiratory failure: a case report

INTRODUCTION: Pleuropulmonary blastoma is a very rare, aggressive, embryonal pulmonary neoplasm which mostly affects children under the age of 5. According to the histopathological features, three subtypes of pleuropulmonary blastoma have been recognized: type I (purely cystic), type II (grossly visible cystic and solid elements) and type III (purely solid). Characteristics of type I and type II blastoma allow an earlier diagnosis compared with type III. Here we present a case report of an unusual presentation of type III pleuropulmonary blastoma. CASE PRESENTATION: We describe the case of a 7-month-old female baby of Italian mother and Kurdish father who was diagnosed with type III pleuropulmonary blastoma, which entirely occupied her right hemithorax. CONCLUSIONS: The reported case is an unusual presentation because type III pleuropulmonary blastoma typically occurs in older children. The complete re-expansion of her residual, previously totally compressed, right lung observed immediately after the resection of the lesion suggests an atypical rapid growth of this embryonal tumor in the late phase of gestation or after delivery. This case report suggests that, in addition to other childhood tumors, type III pleuropulmonary blastoma should be included in the differential diagnosis of solid nonhomogeneous thoracic large masses, compressing the mediastinal and chest wall structures in infants. This is an original case report of interest for several specialities such us pediatrics, radiology, surgery and oncology

Phyllodes Tumors and Fibroadenoma Common Beginning and Different Ending

Phyllodes tumors and fibroadenomas are the most common benign breast tumors. They arise from intralobular fibrous tissue as a unique lesion and after a period of time they differentiate in two direction: to fibroadenoma and to phyllodes tumors. Fibroadenomas grow up to 2–3 cm and then stop growing but phyllodes tumors grow continually and sometimes are to 40 cm big. Both these lesions have two components, epithelial and stromal. Clinically fibroadenomas are well circumscibed, hard, oval, movable lesions. They can be solitary, multiple, unilateral and bilateral. They are hormone dependent changes, because they change their own consistency during menstrual cycle and gravidity. The most commonly used histological classification is in two types: pericanalicular and intracanalicular type. Phyllodes tumors make about 1% of all breast tumors. This tumor has many synonyms. It starts as fibroadenoma in intralobular stromal component. It has continuous growth and biologically it can be benign, borderline and malignant. The first description is from Miller (1838). The main goal is to find the divergence point when the developing is direct to fibroadenoma or phyllodes tumor. The second goal is to investigate the fate of epithelial and stromal component in these two lesions. Retrospective analysis is made of all fibroadenomas and phyllodes tumors in Pathology Department of Medical Center »Be`anijska kosa« in the period from 1998 to 2006. In this period, 2919 women were operated for breast changes. 343 fibroadenoma (24, 4%), were diagnosed, benign phyllodes tumor in 95 women (6.7%) and malignant phyllodes in 4 cases or 0.2%. All slides from these patients were analysed for many different histological parameters and immunohistological investigation for steroid receptors was also used, c-erbB2 (Her2/Neu), PCNA (proliferative cellular nuclear antigen) and Ki-67, androgen receptor and p53. All data were statistically investigated (Odds ratio, confidence interval, Fisher exact test, Wilcoxon sum test and Kendall test). It was concluded that fibroadenomas and phyllodes tumors arise from intralobular fibrous tissue, both changes have very close histology in the beginning and divergent growth starts later. Differences are present in stromal component. Phyllodes tumor has two component stroma. Stromal cells in phyllodes tumors are more PCNA positive than in fibroadenomas, also Ki-67 and androgen receptors are more positive in phyllodes tumors. Histologically phyllodes tumors have perforated capsule with finger like projections. These data determine surgical procedure, wide excision in phyllodes and simple excision in fibroadenomas