Serial lymphoscintigraphic findings in a patient with Gorham's disease with lymphedema.

Gorham's disease is a rare disorder characterized by vascular, "lymphangio- matous" and/or "hemangiomatous" lesions in bone and surrounding soft tissues. Associated lymphedema has not been reported and clinical evolution is unpredictable. Plain radiographs, CT, MRI, and occasionally bone scintigraphy, are used to detect the bone and soft tissues changes. Biopsy is a major component of the diagnostic process. We report the findings of serial lymphoscintigraphy in a young boy with a polyostotic Gorham's disease associated with lymphangioma of the thigh and lower limb lymphedema. In this patient, lymphoscintigraphy was useful for diagnosis and follow-up of primary lymphedema. It provided valuable information concerning the occurrence, location, and progression of lymphatic lesions in both bone and soft tissues.

[Thigh root reconstruction with a pedicled DIEP flap]. / Reconstruction d'une perte de substance de racine de cuisse sur membre lymphœdèmateux par un lambeau DIEP pédiculé

Root thigh extensive loss of substance requires surgical coverage. The presence of chronic lymphedema (LC) makes random with the postoperative healing time longer. We report an original case of reconstruction of extensive loss of substance from the root of the thigh using a pedicled deep inferior epigastric flap perforator (DIEP) flap. A 22-year-old woman with angiosarcoma occurring in hemi-body lymphedema. The defect generated by the oncologic resection was 16×24cm. She was reconstructed by a pedicled DIEP flap. Skin wound healing was obtained within 30 days. Donor site healing was obtained within 15 days. The pedicled DIEP flap seems to be effective for root thigh reconstruction.

Epithelioid hemangio-endothelioma (EHE) in NETSARC: The nationwide series of 267 patients over 12 years.

EPITHELIOID HEMANGIOENDOTHELIOMA: A NATIONWIDE STUDY: Epithelioid hemangioendothelioma (EHE) is an ultrarare sarcoma whose natural history and treatment is not well defined. We report on the presentation and outcome of 267 patients with EHE in the NETSARC+ network since 2010 in France. PATIENTS AND METHODS: NETSARC (netsarc.org) is a network of 26 reference sarcoma centres with specialised multidisciplinary tumour boards (MDTB), funded by the French National Cancer Institute (NCI), Institut National du Cancer (INCA). Since 2010, presentation to an MDTB and second pathological review are mandatory for sarcoma patients. Patients' characteristics are collected in a nationwide database regularly monitored with stable incidence since 2013. The characteristics of patients with EHE at diagnosis are presented as well as progression-free survival (PFS), overall survival (OS), and outcome under treatment. RESULTS: Two hundred and sixty-seven patients with EHE were included in the NETSARC+ database since 2010. Median age in the series was 51 (range 10-90) years, 58% were women. Median tumour size was 37 mm (4-220). Forty-eight percent, 42%, and 10% were visceral, soft parts, or bone primaries. The most frequent sites were liver (28%), lung (13%). 40% were reported to have systemic (i.e. multifocal or metastatic disease) at diagnosis. With a median follow-up of 20 months, OS and PFS rates at 24 months were 82% and 67%, with 10-year projected OS and PFS of 62% and 21% respectively. Male and M+ patients at diagnosis had a significantly worse OS, but not PFS. Local treatment was associated with a favourable survival in localised but not in patients with advanced stage at diagnosis. For 23 patients receiving medical treatment, PFS and OS were 50.2% and 33.2% at 60 months were respectively. CONCLUSIONS: EHE is a frequently metastatic sarcoma at diagnosis with a unique natural history. This study shows in a nationwide series over 12 years that most patients progressed but are still alive at 10 years, both in localised and metastatic stages.

Primary cutaneous Ewing sarcoma: a systematic review focused on treatment and outcome.

BACKGROUND: Despite intensive treatment, the overall prognosis of Ewing sarcoma of the bone remains poor. Primary cutaneous Ewing sarcoma very rarely occurs and the prognosis has been reported to be better in some small series. All cases of Ewing sarcoma are currently treated in the same way, regardless of their location. OBJECTIVES: To determine whether Ewing sarcoma of the bone and primary cutaneous Ewing sarcoma are different in terms of epidemiology and prognosis. METHODS: A systematic review of the literature was carried out using the keywords 'cutaneous Ewing's sarcoma', 'primary Ewing's sarcoma of skin' and 'primary neuroectodermal tumour and skin' in the Medline database. Series of five or more cases were included. RESULTS: Six series met the inclusion criteria, making a total of 61 patients. Median age at diagnosis was 17 years and 33% were male. The median size of the tumour was 2·3 cm. The treatment consisted of surgery in all cases, adjuvant multiagent chemotherapy in 69% of cases, adjuvant chemoradiotherapy in 38% of cases and adjuvant radiotherapy without adjuvant chemotherapy in 3% of cases. Six patients developed metastases, four of whom died. The overall survival was 93% and the 10-year probability of survival was estimated at 91% (95% confidence interval 83-100). CONCLUSION: This systematic review demonstrated epidemiological and prognostic differences between Ewing sarcoma of the bone and primary cutaneous Ewing sarcoma. Primary cutaneous Ewing sarcoma has a female predominance, occurs at a later age, but, more importantly, has a better outcome. Multimodal therapy for Ewing sarcoma is associated with immediate and long-term morbidity and mortality. Although the size of our study does not allow a definitive conclusion about treatment modalities, we suggest that a less toxic approach compared with conventional treatment should be investigated in primary cutaneous Ewing sarcoma.

The Bone Niche of Chondrosarcoma: A Sanctuary for Drug Resistance, Tumour Growth and also a Source of New Therapeutic Targets.

Chondrosarcomas are malignant cartilage-forming tumours representing around 20% of malignant primary tumours of bone and affect mainly adults in the third to sixth decade of life. Unfortunately, the molecular pathways controlling the genesis and the growth of chondrosarcoma cells are still not fully defined. It is well admitted that the invasion of bone by tumour cells affects the balance between early bone resorption and formation and induces an "inflammatory-like" environment which establishes a dialogue between tumour cells and their environment. The bone tumour microenvironment is then described as a sanctuary that contributes to the drug resistance patterns and may control at least in part the tumour growth. The concept of "niche" defined as a specialized microenvironment that can promote the emergence of tumour stem cells and provide all the required factors for their development recently emerges in the literature. The present paper aims to summarize the main evidence sustaining the existence of a specific bone niche in the pathogenesis of chondrosarcomas.

CD44 targeting reduces tumour growth and prevents post-chemotherapy relapse of human breast cancers xenografts.

CD44 is a marker of tumour-initiating cells and is upregulated in invasive breast carcinoma; however, its role in the cancer progression is unknown. Here, we show that antibody-mediated CD44-targeting in human breast cancer xenografts (HBCx) significantly reduces tumour growth and that this effect is associated to induction of growth-inhibiting factors. Moreover, treatment with this antibody prevents tumour relapse after chemotherapy-induced remission in a basal-like HBCx.

[Black bone disease of the skull and facial bones]. / Coloration noire des os du crâne et de la face.

INTRODUCTION: We report the case of a patient with a craniofacial black bone disease. This was discovered accidentally during a coronal approach. CASE REPORT: A 38-year-old patient was referred to our unit for facial palsy having appeared 10 years before. Rehabilitation of the facial palsy was performed with a lengthening temporal myoplasty and lengthening of the upper eyelid elevator. An unusual black color of the skull was observed at incision of the coronal approach. Subperiostal dissection of skull and malars confirmed the presence of a black bone disease. A postoperative history revealed minocycline intake (200mg per day) during 3 years. DISCUSSION: This craniofacial black bone disease was caused by minocycline intake. The originality of this case is to see directly the entire craniofacial skeleton black. This abnormal pigmentation may affect various organs or tissues. Bone pigmentation is irreversible unlike that of the mouth mucosa or of the skin. This abnormal pigmentation is usually discovered accidentally.

Cell-to-cell heterogeneity of EWSR1-FLI1 activity determines proliferation/migration choices in Ewing sarcoma cells.

Ewing sarcoma is characterized by the expression of the chimeric EWSR1-FLI1 transcription factor. Proteomic analyses indicate that the decrease of EWSR1-FLI1 expression leads to major changes in effectors of the dynamics of the actin cytoskeleton and the adhesion processes with a shift from cell-to-cell to cell-matrix adhesion. These changes are associated with a dramatic increase of in vivo cell migration and invasion potential. Importantly, EWSR1-FLI1 expression, evaluated by single-cell RT-ddPCR/immunofluorescence analyses, and activity, assessed by expression of EWSR1-FLI1 downstream targets, are heterogeneous in cell lines and in tumours and can fluctuate along time in a fully reversible process between EWSR1-FLI1high states, characterized by highly active cell proliferation, and EWSR1-FLI1low states where cells have a strong propensity to migrate, invade and metastasize. This new model of phenotypic plasticity proposes that the dynamic fluctuation of the expression level of a dominant oncogene is an intrinsic characteristic of its oncogenic potential.

Light-induced photoactivation of hypericin affects the energy metabolism of human glioma cells by inhibiting hexokinase bound to mitochondria.

Glucose-dependent energy required for glioma metabolism depends on hexokinase, which is mainly bound to mitochondria. A decrease in intracellular pH leads to a release of hexokinase-binding, which in turn decreases glucose phosphorylation, ATP content, and cell proliferation. Thus, intracellular pH might be a target for therapy of gliomas, and a search for agents able to modulate intracellular pH was initiated. Hypericin, a natural photosensitizer, displays numerous biological activities when exposed to light. Its mechanism and site of action at the cellular level remain unclear, but it probably acts by a type II oxygen-dependent photosensitization mechanism producing singlet oxygen. Hypericin is also able to induce a photogenerated intracellular pH drop, which could constitute an alternative mechanism of hypericin action. In human glioma cells treated for 1 h with 2.5 microg/ml hypericin, light exposure induced a fall in intracellular pH. In these conditions, mitochondria-bound hexokinase was inhibited in a light- and dose-dependent manner, associated with a decreased ATP content, a decrease of mitochondrial transmembrane potential, and a depletion of intracellular glutathione. Hexokinase protein was effectively released from mitochondria, as measured by an ELISA using a specific anti-hexokinase antibody. In addition to decreased glutathione, a response to oxidative stress was confirmed by the concomitant increase in mRNA expression of gamma-glutamyl cysteine synthetase, which catalyzes the rate-limiting step in overall glutathione biosynthesis, and is subject to feedback regulation by glutathione. Hypericin also induced a dose- and light-dependent inhibition of [3H]thymidine uptake and induced apoptosis, as demonstrated by annexin V-FITC binding and cell morphology. This study confirmed the mitochondria as a primary target of photodynamic action. The multifaceted action of hypericin involves the alteration of mitochondria-bound hexokinase, initiating a cascade of events that converge to alter the energy metabolism of glioma cells and their survival. In view of the complex mechanism of action of hypericin, further exploration is warranted in a perspective of its clinical application as a potential phototoxic agent in the treatment of glioma tumors.

Rapid maxillary expansion in adults: Can multislice computed tomography help choose between orthopedic or surgical treatment?

INTRODUCTION: The aim of this study was to evaluate the accuracy of Multislice Computed Tomography (MSCT) in the detection resistance areas on the midpalatal suture (MPS) and thus to evaluate if MSCT could be a help in the kind of maxillary expansion to be used (pure orthodontic or surgically-aided) for the correction of transverse maxillary deficiencies in adults. METHODS: Ten MSCT were obtained from 10 MPS removed from fresh corpses (mean age: 79.4; extreme: 70-86). Three standardized radiological regions of interest (ROI) were identified on each MPS and were classified into "open" (group 1) or "closed" (group 2) by 3 independent radiologists. The 30 ROI were then histologically analyzed according to 3 criteria: mean suture width (MSW), obliteration index (OI) and interdigitation index (Ii). RESULTS: Nine ROI were classified in group 1 (closed) and 21 in group 2 (open). On the histological examination, the mean MSW was 396.9µm in group 1 and 227.1µm in group 2. OI was 3.098% and 9.309% and Ii was 1.25 and 1.34 respectively. Statistically significant difference between the 2 groups was only found for the MSW. We conclude that MSCT allows for the evaluation of the width of the MPS, but not for the evaluation of the other possible parameters of resistance we used. Therefore, it cannot predict precisely the amount of résistance in the MPS and is not suited for the choice between pure orthodontic or surgically-aided expansion.

Localized oral Fusarium infection in an AIDS patient with malignant lymphoma.

We report here a case of localized oral Fusarium infection in an AIDS patient who developed an ulceration in the soft palate. Fusarium solani was identified by histopathology and culture. We believe this to be the second reported case of oral Fusarium infection in a patient with haematological malignancy and the first reported association of oral Fusarium infection with AIDS.

Testicular fibroma of gonadal stromal origin with minor sex cord elements: clinicopathologic and immunohistochemical study of 2 cases.

OBJECTIVE: To report the histologic and immunohistochemical features of 2 cases of intratesticular fibromatous tumors. RESULTS: Microscopically, these tumors were composed of short, randomly interweaving fascicles of spindle cells dispersed within a fibrocollagenous stroma. A sex cord component was detected in one case by microscopic examination and in both cases by immunohistochemical study using MIC2 and anti-inhibin antibodies. CONCLUSIONS: The presence of minor sex cord elements, morphologically or by immunohistochemistry, suggests that these fibromatous tumors are related to and are a subset of sex cord-stromal tumors. Intratesticular fibromatous tumors, of which 11 other cases lacking sex cord elements have been reported, could be considered as the testicular equivalent of ovarian fibroma. These tumors could then be referred to as testicular fibroma of gonadal stromal origin, with or without minor sex cord component.

Trichinella murrelli: pathological features in human muscles at different delays after infection.

The authors describe the pathological aspects of muscles of three patients infected with Trichinella murrelli. Biopsies were carried out at various intervals. Six weeks after infection, the muscular larvae were not encapsulated whereas encapsulation was seen 10 weeks after infection. Six years after infection, the larvae were still alive in a nurse cell surrounded by a very thick capsule. Fourteen years after infection, cuticular larvae remnants were seen in degenerating nurse cells. The late encapsulation of Trichinella murrelli in human muscles could explain some clinical differences noticed during the outbreak during which these three patients were infected.

[Chondroblastoma and its differential diagnosis]. / Le chondroblastome et ses pièges diagnostiques.

Chondroblastoma is one of the most well defined cartilaginous tumors of bone on imaging and pathological findings. However in practice, the pathologist is faced with diagnostic difficulties. The most recent features of the tumor are developed in the review: clinical findings, skeletal distribution, and above all, the results of the imaging study which has to be strictly correlated with histology for the diagnosis as well as for the differential diagnosis, location, osteolysis, matrix production, periosteal reactions, MRI studies. Histopathology of chondroblastoma is described: cellular component, architecture, and secondary changes. Usefulness of cytopathology is also stressed on smears or tumor imprints. Main findings of recent and various immunohistochemical stains are described and discussed as well. Ultrastructural and cytogenetic studies are summarized. Treatment, natural history, and prognosis of the tumor are developed. The three most important differential diagnoses are giant cell tumors, clear cell chondrosarcomas, and aneurysmal bone cysts.

[Clear cell sarcoma of the kidney in a young adult]. / Sarcome à cellules claires du rein chez un jeune adulte.

We report a case of clear cell sarcoma of kidney (CCSK), in a young adult. This highly malignant renal tumor usually arises in children of one or two year old and represents 4% of renal tumors. The aggressivity of this tumor and its affinity to give bone metastasis imply to recognize it in order to institute appropriate chemotherapy.

[Renal angiomyolipoma with predominant muscular epithelioid components. 2 cases]. / L'angiomyolipome rénal à composante musculaire épithélioïde prédominante. A propos de deux observations.

We report two cases of pararenal angiomyolipomas, in two middle-aged women without tuberous sclerosis. Both tumors were made of muscular epithelioid cells without atypia, some of which were stained by HMB-45 antibody. The fibrous stroma contained numerous thick-walled blood vessels but no adipose component. The ultrastructural examination revealed that muscular epithelioid cells contained myofilaments and melanosomas. Because of their immunohistochemical and ultrastructural profiles, both tumors may be included in the family of lesions composed of perivascular epithelioid cells (PEC). This tumor type is considered as a particular variant of angiomyolipoma with predominant muscular epithelioid component. The immunohistochemical expression of progesterone and estrogen receptors by both tumors may suggest their hormonodependent character.

[Castleman's disease and chromophobe carcinoma of the kidney. An incidental association?]. / Maladie de Castleman et carcinome chromophobe du rein. Une association fortuite?

We report a case of Castleman's disease in a 65-year-old female, revealed by a renal tumor associated with inter-aortico-cava adenopathies and renal chromophobe cell carcinoma. This observation points to the difficulties in differentiating local Castleman's disease, which may be cured by surgical excision, from multicentric disease associated with a dysimmune syndrome of uncertain prognosis. The association of multicentric Castleman's disease with a carcinoma has rarely been described. It could be the emergence of a neoplasia in a context of dysimmunity or Castleman's disease might be related to the production of interleukin 6 by a renal carcinoma.

[Primary ano-rectal melanoma. Report of 9 cases]. / Les mélanomes primitifs ano-rectaux. A propos de neuf cas.

We report nine cases of anorectal melanoma illustrating the histopathological features of these tumors. In all cases, the diagnosis was made at symptomatic stage. Eight patients were treated by surgical procedure which consisted of abdominal perineal resection or local excision. The tumor was either monomorphous, composed of epithelioid or spindle cells, or polymorphous containing both cell types. One case was characterized by small cells resembling plasma cells. Pigmentation was inconstant. Tumor cells were marked by antibodies directed against the S100 protein (9 cases/9), HMB45 (4 cases/7) and vimentin (5 cases/7). As suggested by these cases, the diagnosis of melanoma should be systematically kept in mind in case of an anorectal tumor with unusual histopathological features.

[A case of hyalinizing spindle cell tumor with giant rosettes in the presacral region. Immunohistochemical and ultrastructural study]. / Un cas de tumeur à cellules fusiformes hyalinisante avec rosettes géantes de la région présacrée. Etude immunohistochimique et ultrastructurale.

Hyalinizing spindle cell tumor with giant rosettes is a slowly growing tumor with a risk of local recurrence in case of incomplete surgical excision that could be regarded as a distinctive type of low-grade fibroblastic tumor. We report a case involving the presacral area. This tumor was composed of areas of bland spindle cell proliferation with a fascicular pattern in a fibrous or myxoid stroma, intermixed with giant rosettes consisting of rounded cells surrounding a central collagen core. The tumor expressed vimentin, and, for cells comprising the rosettes, S-100 protein, NSE and CD-57. These latter cells exhibited ultrastructural features of Schwann cells, the tumoral cells of fascicular area exhibiting features of fibroblastic cells. Flow cytometry showed DNA-aneuploidy and a very low S-phase fraction. This tumor appeared to be composed of two cellular components, fibroblastic and Schwann cells, located, at the opposite of neurofibroma, in two distinct areas.

[Renal medullary carcinoma, a new clinico-pathological entity. Immunohistochemical, ultrastructural, flow cytometric and cytogenetic study of a case]. / Le carcinome médullaire du rein, une nouvelle entité anatomo-clinique. Etude immunohistochimique, ultrastructurale, en cytométrie de flux et cytogénétique d'un cas.

The renal medullary carcinoma is a rare tumor. We report a case in a black patient with sickle cell trait. The tumor was located in the lower pole of the left kidney. It had a tubular and microcystic architecture. It was composed of large eosinophilic cells with vesicular nuclei containing prominent nucleoli, in a desmoplastic and inflammatory stroma. By immunohistochemistry, the tumoral cells were positive for cytokeratin and Ulex europaeus lectin. Electron microscopy revealed small intracytoplasmic lumina with microvilli. The flow cytometric study showed DNA-multiploidy. The cytogenetic study revealed tetraploidy without structural abnormality. The renal medullary carcinoma is often reported in young black patients with sickle cell trait. Its microscopic, immunohistochemical and ultrastructural features favor its identification as a particular variety of Bellini duct carcinoma. Its link with sickle cell trait has to be defined.