Multidisciplinary treatment approach for primary thyroid spindle cell sarcoma: A case report.

A 25-year-old female with high-grade spindle cell sarcoma of the thyroid persistent after thyroidectomy performed at another hospital was referred to our institute. Chemotherapy followed by surgery with intraoperative radiotherapy and postoperative intensity-modulated radiotherapy were planned within the sarcoma board. Chemotherapy was discontinued after two cycles because of local disease progression and surgery with intraoperative radiotherapy, was anticipated. The treatment was completed with postoperative radiotherapy. After 36 months off-therapy, the patient was free of disease without significant late effects. Thyroid sarcomas are very rare and there is no consensus on their clinical management. Hence, case reports are useful to share treatment options. In this patient case, the histotype and the high-grade disease required a combined therapy program, managed in a multidisciplinary setting.

Primary thyroid biphasic synovial sarcoma and synchronous papillary carcinoma: report of a remarkable case.

Synovial Sarcoma (SS) is the fourth most common soft tissue sarcoma, characterized by translocation t(X;18) (p11.2;q11.2). Although its histological features have been extensively described, this entity is characterized by a wide morphological spectrum so that the recognition can be very challenging at atypical anatomical localization, like the thyroid. We describe a case of a 42-ys-old female patient complaining a cervical swelling due to left intrathyroid nodule, measuring 35 mm in its greatest dimension. A Fine Needle Aspiration Cytology (FNAC) was performed and diagnosis of indeterminate neoplastic lesion, indefinite whether primary or metastatic, was formulated. After complete thyroidectomy, the histological picture of the nodule was characterized by a dual cellular population: several glandular structures composed by columnar cells with clear cytoplasm were embedded in a highly cellular stroma composed of spindle-shaped elements. Immunohistochemistry and molecular biology confirmed the morphological suspicion of SS identifying the fusion transcript SYT-SSX1 and thus ruling out several differential diagnoses which include more common thyroid malignancies. Moreover a synchronous papillary microcarcinoma was detected in the controlateral lobe.This case is noteworthy since it describes the synchronous presence in the thyroid of two completely different malignancies, the first one belonging to the soft tissue neoplasm category and the other one originating from the thyroid follicular epithelium.

Long-term Follow-up and Post-relapse Outcome of Patients with Localized Retroperitoneal Sarcoma Treated in the Italian Sarcoma Group-Soft Tissue Sarcoma (ISG-STS) Protocol 0303.

BACKGROUND: This study was designed to assess patterns of recurrence and long-term outcomes of patients undergoing surgery for localized retroperitoneal sarcoma (RPS) after neoadjuvant high dose long-infusion ifosfamide (HLI) and radiotherapy (RT). METHODS: Patients received three cycles of HLI (14 g/m2). RT was started in combination with II cycle up to a total dose of 50.4 Gy. Surgery was scheduled 4-6 weeks after the end of RT. The primary endpoint was relapse-free survival (RFS) after surgery. Secondary endpoints were overall survival (OS), crude cumulative incidence of local recurrence (CCI-LR), and distant metastases (CCI-DM). For patients who relapsed, progression-free survival (PFS) and post-relapse OS were estimated. The trial was registered with ITASARC_*II_2004_003. RESULTS: Between 2003 and 2010, 83 patients were recruited. At a median follow-up of 91.7 months, 42 (56%) of 75 operated patients developed LR (n = 27) or DM (n = 10) or both LR and DM (n = 5) relapse. Seven-year RFS was 46.6% [95% confidence interval (CI) 29.6-52.4]. Thirty-two patients died. Seven-year OS rate was 63.2% (95% CI 42.7-66.0). The corresponding CCI of LR and DM were 37.4% [standard error (SE) 5.5%] and 20.0% (SE 12.6%), respectively. The only factor significantly associated with LR was FNCLCC grading, whereas histological subtype resulted associated with DM. At recurrence, 24 patients (57%) underwent surgery. Two-year post-relapse PFS and OS rates for patients developing LR or DM were 14.8, 41.0, 27.3, and 63.6%, respectively. CONCLUSIONS: LR after neoadjuvant CT-RT for RPS were predominantly infield. While almost one half of relapsed patients underwent further surgery, prognosis was poor.

Multimodal approach of advanced gastric cancer: based therapeutic algorithm.

Gastric cancer (GC) is the third leading cause of cancer death in both sexes worldwide, with the highest estimated mortality rates in Eastern Asia and the lowest in Northern America. However, the availability of modern treatment has improved the survival and the prognosis is often poor due to biological characteristics of the disease. In oncology, we are living in the "Era" of target treatment and, to know biological aspects, prognostic factors and predictive response informations to therapy in GC is mandatory to apply the best strategy of treatment.The purpose of this review, according to the recently published English literature, is to summarize existing data on prognostic aspects and predictive factors to response to therapy in GC and to analyze also others therapeutic approaches (surgery and radiotherapy) in locally, locally advanced and advanced GC. Moreover, the multidisciplinary approach (chemotherapy, surgery and radiotherapy) can improve the prognosis of GC. The purpose of this review, according to the recently published English literature, is to summarize existing data on prognostic aspects and predictive factors to response to therapy in GC and to analyze also others therapeutic approaches (surgery and radiotherapy) in locally, locally advanced and advanced GC. Moreover, the multidisciplinary approach (chemotherapy, surgery and radiotherapy) can improve the prognosis of GC.

Intraoperative radiation therapy for retroperitoneal soft tissue sarcomas.

Treatment of retroperitoneal soft tissue sarcomas is a difficult clinical problem. Despite the improvement in resection rates in the most recent surgical series, local control still remains the main problem because of the high incidence of local recurrences after surgery. Postoperative radiation therapy has not been always successful because of dose-tolerance of surrounding normal structures, which prevent the delivery of adequate doses of radiation. To overcome this limitations, new therapeutic approaches including external-beam radiation and intraoperative radiation therapy (IORT) have been evaluated at some Institutions. The results of IORT with or without external-beam radiation are reviewed and our experience with preoperative radiation and IORT is reported. As treatment of retroperitoneal sarcomas has evolved into combined modalities including preoperative radiation, maximum surgical resection and IORT, a possible improvement in local control rates has been achieved. However, locoregional failures and the incidence of distant metastases remain a challenge, emphasising the need for further improvement in local and distant treatment. The new phase II trial, activated within the Italian Sarcoma Group, with preoperative concurrent chemo-radiation therapy and IORT is presented.

[Hypopituitarism in the elderly at an internal medicine department]. / Ipopituitarismo in età geriatrica in un Reparto di Medicina interna.

We describe three cases of hypopituitarism with empty sella in elderly patients. Hypopituitarism in geriatric population is not uncommon, but is oftern underestimated and confused with more frequent diseases. It can sometimes determine severe clinical picture, above all for the consequences of adronocortical insufficiency. We emphasize that empty sella is not always an asymptomatic radiological finding.

Metastatic angiosarcoma of the spleen. A case report and treatment approach.

We report a case of a 28-year-old man with angiosarcoma of the spleen and liver metastases. The aim of this paper is to underline the importance of planned splenectomy in these patients even if they have metastatic disease, and to propose an intensive chemotherapy regimen consisting of anthracyclines, ifosfamide and mesna with G-CSF support.

[Hematological changes in hyperthyroidism. A case report]. / Alterazioni ematologiche in corso di ipertiroidismo. Descrizione di un caso.

A case of microcytic anemia, leukopenia (with lymphocytic reduction prevalence) and light thrombocytopenia is reported. The case occurred to a 63-year old diabetic woman suffering from Basedow's disease. The thyropathy was diagnosed first and the patient did not undergo to any previous treatment with antithyroid agents. The bone marrow aspiration only showed slight dyserythropoietic notes, with slight reduction of myeloid-erythroid ratio. The blood cell indexes rapidly normalized as soon as euthyroidism was achieved by radioiodine therapy (I131, 4mCi), and this led to think there was a relationship between thyropathy and blood modifications. The patient was subsequently treated with levothyroxine because of the occurrence of a iatrogenic hypothyroidism. Two years later, during a follow-up, all the hematologic parameters were normal, as well as the serum concentration of thyroid hormones and TSH (during opotherapy). We report the hematologic alterations most frequently observed in hyperthyroidism and underline the peculiarity of this case as it shows the simultaneous alterations of different cellular lines in the same patient.

High dose dexamethasone as first line therapy of multiple myeloma? A case report.

The authors describe a case of multiple myeloma in which a complete remission was obtained by treatment with high dose dexamethasone. This was the only therapy suitable for the patient because of heavy myelosuppression due to disease and to one course of conventional treatment with melphalan and prednisone. Further trials are needed to evaluate the usefulness and safety of this treatment as first line therapy, especially in the elderly, with pancytopenia and bad performance status.

Can a specifically-aimed pathologic classification overcome the difficulties in defining HIV-associated lymphomas?

High grade B-cell systemic lymphomas in HIV-infected patients exhibit pleomorphic features as well as some overlap between established histologic subtypes thus highlighting the difficulties in defining them precisely by making use of the classifications for non-Hodgkin's lymphomas (NHL) proposed before the AIDS epidemic. A series of HIV-associated systemic lymphomas including 114 NHL and 25 Hodgkin's disease (HD) cases were morphologically and immunopheno-genotypically investigated at the Centro di Riferimento Oncologico, Aviano, Italy during a period of nine years. The International Working Formulation (WF) for NHL, the updated Kiel Classification and, later, morphologic variants of high grade B-cell NHL have been adopted in order to obtain a more detailed and specific histopathologic description of HIV-associated lymphomas. As a consequence of morphologic data, and considering also pathogenetic aspects as derived from literature, we have attempted a pathological categorization of HIV-associated systemic lymphomas based on the recognition of two main groups: the "blastic" cell group and the "anaplastic" one, both including specific cytomorphologic subtypes with, possibly, aggressive HD subtypes within one of them. This categorization uses the WF, the updated Kiel system, and the morphologic variants of high-grade lymphomas, and provides a provisional category for cases with intermediate morphologic features. Thus other histologic subtypes, such as small noncleaved cell (Burkitt) and immunoblastic lymphomas, can be defined in a more accurate way. The clear-cut placement of "anaplastic" cell lymphomas, including anaplastic large cell (CD30/Ki-1+) lymphomas, including anaplastic large cell (CD30/Ki-1+) lymphomas and possibly a proportion of HD cases, emphasizes the need for their diagnostic differentiation from polymorphic "blastic"' cell lymphomas, immunoblastic ones in particular.

Primary gastric non-Hodgkin's lymphoma--does surgery still play any role?

36 patients with primary gastric non-Hodgkin's lymphoma (PGL) (stage Ie and IIe) were treated at the Comprehensive Cancer Center of Aviano (PN) Italy. The median follow-up time of the patients was 59 months (range 10 to 117). The pre-operative diagnosis of PGL was established by using endoscopy in 70% of the patients. There was understaging in non-invasive methods of diagnosis in comparison to laparotomy. Prognostic factors such as: stage, grade according to the Working Formulation, size, depth of penetration of the gastric wall and resectability of the tumor, were taken into consideration in the treatment plan. This consisted of surgical resection of the gastric lymphoma where feasible and according to the bad prognostic factors escalating adjuvant treatment was included: group I (n = 6) patients were treated only by surgery (S), II (n = 8) by S+radiotherapy (RT) (n = 5) or S+chemotherapy (CT) (n = 3), III (n = 17) by S+RT+CT and IV (n = 5) by non-resectable S+RT+CT. There were no statistically significant differences in the survival rate, calculated by Kaplan-Meier method, between the first three groups of patients. Only stage of disease (P = 0.048) and resectability of the lesion (P = 0.003) had a significant influence on survival. There were no serious complications observed in either S, RT or CT treatment. The estimated 5-year survival rate after management was 100%, 75% and 88%, respectively for stage Ie (n = 21), stage IIe (n = 15) and all together.

Differential expression of cell adhesion molecules CD54/CD11a and CD58/CD2 by human melanoma cells and functional role in their interaction with cytotoxic cells.

Immunohistochemical staining with monoclonal antibodies showed a differential distribution of intercellular adhesion molecule 1 (ICAM-1/CD54) and lymphocyte function-associated antigen 3 (LFA-3/CD58) and their respective counterreceptors lymphocyte function-associated antigens 1 (LFA-1/CD11a) and 2 (LFA-2/CD2) on ten melanoma cell lines and in 46 surgically removed metastatic melanoma lesions. CD11a and CD2 were not detected on melanoma cells while CD54 and CD58 were coexpressed on the majority of the melanoma cell populations investigated. CD54 showed a higher degree of intra- and intertumor heterogeneity than CD58. gamma-Interferon and/or tumor necrosis factor alpha upregulated the expression of CD54 by melanoma cells, but neither modulated that of CD58 nor induced that of CD11a and CD2. Anti-CD54 and anti-CD58 monoclonal antibodies partially inhibited the lysis of melanoma cells by allogeneic natural killer cells, lymphokine-activated killer cells and, to a greater extent, by autologous tumor-infiltrating lymphocytes. Soluble CD54 (cCD54) purified from serum of patients with melanoma inhibited the lysis of melanoma cells F0-1 by natural killer cells in a dose-dependent fashion. These results suggest that membrane-bound CD54 and CD58 and cCD54 play a role in host-tumor interactions in patients with malignant melanoma and may account for the relationship between CD54 expression in primary lesions and the clinical course of disease.

High incidence of monoclonal EBV episomes in Hodgkin's disease and anaplastic large-cell KI-1-positive lymphomas in HIV-1-positive patients.

A series of selected lymphoid malignancies (LMs) occurring in Italian HIV-1-infected (HIV+) patients, principally intravenous drug users, was investigated. In addition to small non-cleaved-cell (SNCC) and large-cell immunoblastic (LCI) non-Hodgkin's lymphomas (NHLs), a relatively high occurrence of anaplastic large-cell Ki-I-positive (ALC Ki-I+) lymphomas and Hodgkin's disease (HD) was observed, at variance with other reported series of HIV+ patients. Combined results of in situ hybridization and Southern-blot analyses, in conjunction with immunohistochemical detection of Epstein-Barr virus (EBV)-encoded latent membrane protein-I (LMP-I), showed an almost complete association of ALC Ki-I+ lymphomas and HD cases with EBV. The neoplastic cells of both these LMs also showed common immunophenotypic features such as frequent absence of B- and T-cell differentiation markers and expression of the Ki-I activation marker, while SNCC and LCI lymphomas were mainly of mature B-cell origin and Ki-I-. The concomitant high incidence of ALC Ki-I+ lymphomas and HD in a specific group of HIV+ patients, their almost complete association with EBV in clonal and episomal form and the great similarity in differentiation, activation and virological markers which they display suggest that these LMs are pathological variants of a continuous spectrum of HIV-I-associated disorders etiopathologically linked to EBV.

Hodgkin's disease in 92 patients with HIV infection: the Italian experience. GICAT (Italian Cooperative Group on AIDS & Tumors).

Ninety-two cases of Hodgkin's disease (HD) in patients with HIV infection have been collected by the Italian Cooperative Group on AIDS and Tumors (G.I.C.A.T.). In accordance with the epidemiology of HIV infection in Italy, 82% were intravenous drug users (IVDU), 8% homosexual men, 5% IVDU+homosexuals and 5% heterosexuals. At diagnosis of HD, 16% had AIDS, 20% AIDS related complex (ARC), 33% persistent generalized lymphadenopathy (PGL) and 31% were asymptomatic. Fifty-three percent of the patients had stage IV disease and 70% mixed cellularity and lymphocytic depletion. Forty-six patients were treated with MOPP or MOPP [symbol: see text] ABVD +/- radiotherapy (zidovudine was not given) with complete remission (CR) in 54% and partial remission (PR) in 46% of the patients. Fifty-six percent of these patients developed opportunistic infections (OI) during therapy or follow-up. Sixteen patients were treated with epirubicin, bleomycin and vinblastine (EBV) and concomitant zidovudine, with CR in 44% and PR in 38%. However, only one of these patients developed OI during therapy or follow-up. The clinico-pathological features and natural history of HD in HIV setting are peculiar and quite distinct from those observed in HD in the general population. Better combined chemotherapy and antiretroviral therapy is needed in order to ameliorate the CR rate and decrease the OI in patients with HIV infection and HD.

Radiation therapy and conservative surgery for soft tissue sarcomas of the extremities, torso and head and neck.

Between May 1985 and July 1990, 45 patients (pts.) with primary (39) or recurrent (6) soft tissue sarcomas of the extremities (82%), torso (11%) and head and neck (7%) were treated with radiation therapy and conservative surgery. Seven pts. not amenable to conservative surgery underwent preoperative radiation therapy whereas 38 pts. underwent local excision and post-operative radiation therapy. Out of the 38 pts. managed by postoperative radiation, 24 (63%) showed negative surgical margins and 14 (37%) positive margins, their tumor being adjacent to vital structures. Preoperative radiation allowed conservative surgery in all 7 pts. with initially inoperable tumor; surgical margins were negative in 5 and positive in 2 pts. Twenty-six pts. (58%) had tumor greater than or equal to 5 cm (5-24) and 19 (42%) less than 5 cm (2.5-4.5) in diameter. High grade tumors (G2-G3) were reported in 41 pts. (90%). In pts. treated postoperatively the radiation dose was 64-66 Gy/32-33 fractions and the pts. treated preoperatively received a dose of 50 Gy/25 fractions. Median follow-up was 33 months and all pts. had a minimum follow-up of 12 months (12-72). Three pts. (6.5%) had local failure and 9 (20%) developed distant metastases with local tumor control. All distant metastases occurred in AJC stage IIIB, 9/18 (50%), with an increased frequency by tumor size. Overall local control and disease free survival rates at 5 years (product-limit method) were 93% and 73%, respectively. An evident decrease in disease-free survival rate (33%) was noted for stage IIIB pts.(ABSTRACT TRUNCATED AT 250 WORDS)

A clinicopathologic study of lymphoid neoplasias associated with human immunodeficiency virus infection in Italy.

The clinicopathologic features of 45 human immunodeficiency virus (HIV)-infected patients (mainly intravenous drug users [IVDU]) with lymphoid neoplasias seen from September 1984 through July 1990 at an Italian cancer center are reviewed. Thirty-five had systemic non-Hodgkin's lymphoma (NHL), and ten had Hodgkin's disease (HD). Histologically, 27 NHL cases were intermediate grade (five cases) or high grade (22 cases, 14 of the small noncleaved cell type), according to the Working Formulation. Eight NHL cases, including four anaplastic large cell (ALC) BerH2 (CD30)-positive lymphomas, were in the miscellaneous group. Immunohistologic and/or gene rearrangement analysis showed the B-cell origin of 20 of the 24 NHL cases studied. At presentation, 71% of NHL patients had advanced stages (Stage III or IV), and 85% had extranodal disease (predominantly gastrointestinal tract and marrow). Of the 23 patients evaluable for treatment, only seven had a complete clinical response after lymphoma therapy; the median survival of 34 evaluable patients was 22 months after the diagnosis of NHL. Fifteen patients died; most deaths were attributable to progressive lymphoma and opportunistic infections. As with NHL, advanced disease, extranodal involvement, aggressive histologic findings, and poor response to therapy were also observed in patients with HD. This study shows that lymphoid neoplasias occurring in Italian IVDU with HIV infection and those previously reported in North American homosexual men with HIV infection share similar clinicopathologic features. However, some features such as the absence of history of Kaposi's sarcoma at diagnosis, the lack of detection of primary brain and rectal NHL, and the occurrence of B-cell ALC BerH2 (CD30)-positive NHL were observed uniquely in this series of patients.

Changes in the hypothalamic-pituitary somatotropic function of infant hypothyroid rats.

The effects of the perturbation of the pituitary-thyroid axis induced during development on the functional activity of the growth hormone (GH) regulatory neuronal systems, GH-releasing hormone (GHRH), and somatostatin (SS) were studied in 14- and 21-day-old rats made hypothyroid by giving dams propylthiouracil in the drinking water since the day of parturition. Infant hypothyroid rats, both at 14 and 21 days of life, had elevated plasma thyroid-stimulating hormone levels and decreased pituitary and plasma GH levels. Simultaneous determination of hypothalamic GHRH/SS-like immunoreactivity (LI) and GHRH/SS mRNA levels did not reveal any difference in 14-day-old hypothyroid rats when compared with age-matched controls. In contrast, 21-day-old hypothyroid rats had decreased GHRH-LI content and a striking rise in GHRH mRNA levels, whereas SS-LI content and SS gene expression remained unaltered. These data indicate that in infant hypothyroid rats, changes in the functional activity of the GHRH neuronal system occur later than changes in GH secretion and are probably dependent on the GH deficiency. The functional activity of SS neurons was apparently unaltered in these hypothyroid rats, pointing to a lesser sensitivity of this system to the perturbation of the pituitary-thyroid axis.

Persistent generalized lymphadenopathy syndrome vs "AIDS"--unrelated malignant lymphoma: comparison of presenting clinical and laboratory findings in 88 patients. AIDS and Related Syndromes Study Group.

The purpose of this report is to document and compare the presenting clinical and laboratory findings of 38 patients, all intravenous drug abusers, with pathologically documented persistent generalized lymphadenopathy (PGL), and of 50 patients with AIDS-unrelated malignant lymphoma (30 with Hodgkin's disease and 20 with non-Hodgkin's lymphoma). All patients, aged 40 years or less, consecutively seen since May 1984 in a single institution in Italy, have prospectively undergone a similar clinico-pathologic approach. In addition to a history of intravenous drug abuse and HIV serology, the results indicate that a history of infection in the previous year, night sweats, weight loss, generalized lymphadenopathy, beta 2 microglobuline, transaminase, T4/T8 ratio less than 1, and polyclonal hypergamma-globulinemia significantly increased among PGL patients compared with patients with AIDS-unrelated malignant lymphoma. In contrast, patients with malignant lymphoma had a significant increase in mediastinal lymph nodes, sedimentation rate, LDH, fibrinogen and anemia. Therefore, at this time of an AIDS epidemic, after histologic diagnosis of reactive lymphadenopathy has been performed in young patients presenting with generalized lymphadenopathy, a request for a second biopsy and other invasive procedures may be avoided if clinical and laboratory data suggest a PGL syndrome. If not already performed, HIV antibody detection should be carried out in this setting.