A clinical-molecular prognostic model to predict survival in patients with post polycythemia vera and post essential thrombocythemia myelofibrosis.

Polycythemia vera (PV) and essential thrombocythemia (ET) are myeloproliferative neoplasms with variable risk of evolution into post-PV and post-ET myelofibrosis, from now on referred to as secondary myelofibrosis (SMF). No specific tools have been defined for risk stratification in SMF. To develop a prognostic model for predicting survival, we studied 685 JAK2, CALR, and MPL annotated patients with SMF. Median survival of the whole cohort was 9.3 years (95% CI: 8-not reached-NR-). Through penalized Cox regressions we identified negative predictors of survival and according to beta risk coefficients we assigned 2 points to hemoglobin level <11 g/dl, to circulating blasts ⩾3%, and to CALR-unmutated genotype, 1 point to platelet count <150 × 109/l and to constitutional symptoms, and 0.15 points to any year of age. Myelofibrosis Secondary to PV and ET-Prognostic Model (MYSEC-PM) allocated SMF patients into four risk categories with different survival (P<0.0001): low (median survival NR; 133 patients), intermediate-1 (9.3 years, 95% CI: 8.1-NR; 245 patients), intermediate-2 (4.4 years, 95% CI: 3.2-7.9; 126 patients), and high risk (2 years, 95% CI: 1.7-3.9; 75 patients). Finally, we found that the MYSEC-PM represents the most appropriate tool for SMF decision-making to be used in clinical and trial settings.

CALR vs JAK2 vs MPL-mutated or triple-negative myelofibrosis: clinical, cytogenetic and molecular comparisons.

Calreticulin (CALR) mutations were recently described in JAK2 and MPL unmutated primary myelofibrosis (PMF) and essential thrombocythemia. In the current study, we compared the clinical, cytogenetic and molecular features of patients with PMF with or without CALR, JAK2 or MPL mutations. Among 254 study patients, 147 (58%) harbored JAK2, 63 (25%) CALR and 21 (8.3%) MPL mutations; 22 (8.7%) patients were negative for all three mutations, whereas one patient expressed both JAK2 and CALR mutations. Study patients were also screened for ASXL1 (31%), EZH2 (6%), IDH (4%), SRSF2 (12%), SF3B1 (7%) and U2AF1 (16%) mutations. In univariate analysis, CALR mutations were associated with younger age (P<0.0001), higher platelet count (P<0.0001) and lower DIPSS-plus score (P=0.02). CALR-mutated patients were also less likely to be anemic, require transfusions or display leukocytosis. Spliceosome mutations were infrequent (P=0.0001) in CALR-mutated patients, but no other molecular or cytogenetic associations were evident. In multivariable analysis, CALR mutations had a favorable impact on survival that was independent of both DIPSS-plus risk and ASXL1 mutation status (P=0.001; HR 3.4 for triple-negative and 2.2 for JAK2-mutated). Triple-negative patients also displayed inferior LFS (P=0.003). The current study identifies 'CALR(-)ASXL1(+)' and 'triple-negative' as high-risk molecular signatures in PMF.

Circulating cytokeratin 19 fragments in patients with benign nodules and carcinomas of the thyroid gland.

Cytokeratin 19 (CK19) is an acidic protein of 40 kDa that is part of the cytoskeleton of epithelial cells and is highly expressed by differentiated thyroid carcinomas, mainly of the papillary subtype. The soluble fragments of CK19 (Cyfra 21.1) can be measured by immunometric assays employing specific monoclonal antibodies. The present study was planned to assess the serum expression of Cyfra 21.1 in patients with benign thyroid nodules and thyroid malignancies. We enrolled 135 patients with histologically proven benign thyroid nodules (n=79) and thyroid carcinomas (n=56). No differences were found in serum Cyfra 21.1 levels between patients with benign nodules and patients with carcinomas. When thyroid malignancies were subdivided according to tumor histology, serum Cyfra 21.1 increased significantly from classical differentiated thyroid carcinomas (papillary or follicular) to less differentiated or undifferentiated carcinomas (poorly differentiated or anaplastic). CK19 release into the bloodstream is strongly related to the apoptotic pathway, and particularly to hyperproliferation-related apoptosis. These pathways characterized anaplastic and poorly differentiated thyroid carcinoma but not classical forms of differentiated thyroid carcinoma. Consequently, Cyfra 21.1 may be regarded as a circulating marker of poorly differentiated and anaplastic thyroid carcinoma. Additionally, a role of Cyfra 21.1 as a dedifferentiation marker in patients with classical differentiated thyroid carcinomas may be postulated and should be explored by further focused studies.

Flow cytometry evaluation of erythroid dysplasia in patients with myelodysplastic syndrome.

Erythroid dysplasia is the pathologic hallmark of myelodysplastic syndromes (MDS). To develop a quantitative flow-cytometry approach to its evaluation, we analyzed the expression of CD71, CD105, cytosolic H-ferritin (HF), cytosolic L-ferritin (LF) and mitochondrial ferritin (MtF) in erythroblasts from 104 MDS patients, 69 pathologic control patients and 19 healthy subjects. Six-parameter, 4-color flow cytometry was employed, and data were expressed as mean fluorescence intensity. Compared with pathologic and healthy controls, MDS patients had higher expression of HF (P < 0.001) and CD105 (P < 0.001), and lower expression of CD71 (P < 0.001). MtF was specifically detected in MDS with ringed sideroblasts, and there was a close relationship between its expression and Prussian blue staining (r = 0.89, P < 0.001). In vitro cultures of myelodysplastic hematopoietic progenitors showed that both HF and MtF were expressed at a very early stage of erythroid differentiation, and that MtF expression is specifically related to mitochondrial iron loading. A classification function based on expression levels of HF, CD71 and CD105 allowed us to correctly classify > 95% of MDS patients. This flow-cytometry approach provides an accurate quantitative evaluation of erythroid dysplasia and allows a reliable diagnosis of sideroblastic anemia, and may therefore be a useful tool in the work-up of patients with MDS.

Flow cytometry evaluation of erythroid and myeloid dysplasia in patients with myelodysplastic syndrome.

The purpose of this study was to develop a flow cytometric approach to the evaluation of marrow dysplasia in myelodysplastic syndromes (MDS). We first studied a cohort of 103 MDS patients as well as 46 pathological and healthy controls. Flow cytometry data were expressed as percentage of positive cells. Analysis of erythroid cells showed higher proportions of immature cells (P < 0.001) and decreased levels of CD71 expression on nucleated red cells (P = 0.02) in MDS. Analysis of myeloid cells showed lower proportions of CD10+ and higher proportions of CD56+ granulocytes (P < 0.001), and increased ratios of immature to mature cells (P = 0.007). Since no single immunophenotype could accurately differentiate MDS from other conditions, we used discriminant analysis for generating erythroid and myeloid classification functions using combinations of immunophenotypic parameters. These functions were prospectively validated in a testing cohort of 69 MDS patients and 46 pathological controls. A diagnosis of MDS was obtained in 60/69 cases (87%). No false-positive results were noticed among controls. Significant correlations between values of these functions and both degree of morphological dysplasia and the International Prognostic Scoring System were found. These findings indicate that flow cytometry evaluation of marrow dysplasia is feasible and may be useful in the work-up of individual MDS patients.

[Solitary fibrous tumor of the nasopharynx. Apropos of a case]. / Tumeur fibreuse solitaire du nasopharynx. A propos d'un cas.

Solitary fibrous tumor (SFT) is a rare neoplasm, arising in the adult and more commonly in the pleura. For many years it has been referred to the serous surfaces of the body, namely pleura, peritoneum and pericardium; recently cases arising in mesenchymal organs such as lung, mediastinum, liver and paranasal sinuses were reported. We present a SFT of the nasopharynx, observed in a 41 year-old patient complaining a 6 months history of aural fullness at the right ear. Clinical examination revealed the presence of secretory otitis media and swelling of the lateral wall of the nasopharynx. CT scan and MR showed the presence of a solid mass, with scarce vascularization, extending from the right side of the nasopharynx to the infratemporal and pterigoid fossae. The surgical approach consisted in a facial translocation by the rotation of a maxillary-check flap through different osteotomies; a firm whitish mass not invading the surrounding tissues was identified and enucleated. A definitive diagnosis cannot be made at frozen sections, requiring more accurate processing and immunohistochemical staining. Literature reports fourteen cases of SFT of the upper aero-digestive tracts (nasopharynx, paranasal sinuses, larynx) and some 8 more cases in the head and neck area (thyroid, salivary glands and parapharyngeal spaces). This case report adds a further contribution to support the mesenchymal origin of the SFT.

[Cutaneous head and neck carcinomas: biological characteristics, natural history and clinical classification]. / I carcinomi cutanei della testa e del collo: caratterizzazione biologica, storia naturale e classificazioni cliniche.

In cutaneous carcinoma of the Head and Neck there is a 7% of cases that often suffer substantial morbidity and even mortality. The identification of the "high-risk patient" may derive from the study of the prognostic factors which have been published in Literature. The problem has to be differentiated between the basal cells carcinoma (BCC) and the squamous cells carcinoma (SCC) due to the locally limited aggressiveness of the first and the potential for metastatization of the latter. The evaluation of the different variables confirms the inadequacy of the present TNM Classification for Cutaneous carcinoma; nevertheless the opportunity of a new and omni-comprehensive proposal is questionable.

[Primary lymphoma of the sphenoid sinus. Report of a case and review of the literature]. / Lymphome primitif du sinus sphénoïdal. Présentation d'un cas et révision de la littérature.

The Authors describe a case of primary isolated non-Hodgkin lymphoma with sphenoidal presentation. According to literature, this is the third specification quoted in the whole world. The diagnostic approach for this clinical entity is emphasized, stressing the importance of the complete radiological and endoscopic work-up.

Hypopharyngeal reconstruction using a pectoralis major myofascial flap / Reconstrucción de hipofaringe con un colgajo músculo aponeurótico del pectoral mayor

Se describe una técnica para reconstrucción hipofaríngea usando un colgajo músculo-aponeurótico y se comunican los resultados en tres pacientes. Las ventajas de la técnica son que, gracias a que es un injerto delgado y versátil, ofrece una menor posibilidad de que haya dehiscencia de la herida y, a la vez, una mayor probabilidad de desarrollar mejor voz esofágica. Deja una buena apariencia cosmética en el pecho y no crece cabello en el colgajo.

[Prospective, cohort, epidemiologic studies of laryngeal neoplasms in Italy]. / Studio prospettico probabilistico per effetto coorte sull'incidenza del cancro della laringe in Italia.

Recent epidemiological studies show, quite surprisingly, a regression in mortality rates for lung cancer in some of the most industrialized countries of the world. Aetiopathogenetic analogies are made by the Authors in order to verify future trends concerning the incidence of laryngeal cancer in Italy. In this study a particular study model, which furnishes incidence rate expectations for the disease, is elaborated. Comparison of relative risks according to birth dates demonstrates that people born around 1930 are in the higher risk range while younger generations seem to show an effective incidence reduction. Evaluations include that of estimating the period in which the world-wide incidence of the disease will be maximum. With the addition of 70 years (main incidence in the seventh decade) to the year 1930 (the worst year) the study predicts that the end of this century will see the most consistent accumulation of new cases. After the year 2010 a trend towards a gradual regression in incidence will appear. The reasons are probably related to the social and cultural transformations of the last twenty years, particularly the progressive abandoning of the smoking habit.

[Temporal bone metastasis of adenocarcinoma of the breast: personal observations and a review of the literature]. / Metastasi temporale da adenocarcinoma mammario: osservazione personale e revisione della letteratura.

A single case of temporal bone metastases from breast carcinoma is reported and its clinical features and main instrumental diagnostic characteristics are described. Although this is quite rare the possibility cannot be neglected when making diagnosis should the clinical features and test results suggest such an expansive process of the temporal bone. In fact, although extremely limited, treatment is strictly linked to proper and early diagnosis.

[Salvage surgery after unsuccessful radiotherapy of cancer of the larynx]. / Chirurgia di recupero dopo insuccesso radioterapico nel cancro della laringe.

The problem of the surgical management of irradiation failures in laryngeal carcinoma is taken into consideration. A series of 60 consecutive laryngectomies performed at the E.N.T. Department of the Regional Hospital of Varese from 1982-1987 is presented. All patients had previously undergone curative radiotherapy for squamous cell carcinoma of the larynx with subsequent local recurrence. The postoperative course is examined in relation to the observed 11 cases of complications (18.3%) taking them into consideration individually. A statistical analysis is also presented for the incidence of complications in relation to the most significant parameters. No significant difference was found in regard to timer elapsed since termination of radiotherapy (more or less than 6 months), irradiation field extension (limited to the larynx or extended to the neck nodes), type of surgical salvage (including neck dissection or not) and pre-operative hemoglobin and blood proteins values. In those patients who had previously undergone irradiation, total laryngectomy is quite a safe procedure in terms of potential local-regional complications. The choice of primary radiotherapy should not be influenced by the fear of such complications arising if salvage surgery is required after local recurrence.

Protection from hyperbaric oxygen intoxication by some derivatives of alfa-ketoglutaric acid.

A study was made of the protective effects afforded by some derivatives of alpha-ketoglutaric acid in hyperbaric oxygen intoxication. The research performed shows that these substances are able either to prevent convulsions (Paul Bert phenomenon) or to prolong the survival of treated animals. Brain ATP rates and liver succinyl dehydrogenase activity, which normally decrease in hyperbaric oxygen intoxication, are also very high after protective treatment with these substances.