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Thymic epithelial tumors (TETs) are rare malignancies associated with dysregulation of the immune system and humoral- and cell-mediated immunity abnormalities. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine is effective in preventing coronavirus disease 2019 morbidity and mortality. The aim of this study was to evaluate the seroconversion in patients with TET after two doses of mRNA vaccine.

Purpose: Many different treatments are suggested by guidelines to treat grade 1-2 (G1-G2) neuroendocrine tumors (NET). However, a precise therapeutic algorithm has not yet been established. This study aims at identifying and comparing the main therapeutic sequences in G1-G2 NET. Methods: A retrospective observational Italian multicenter study was designed to collect data on therapeutic sequences in NET. Median progression-free survival (PFS) was compared between therapeutic sequences, as well as the number and grade of side effects and the rate of dose reduction/treatment discontinuation. Results: Among 1182 patients with neuroendocrine neoplasia included in the ELIOS database, 131 G1–G2 gastroenteropancreatic, lung and unknown primary NET, unresectable or persistent/relapsing after surgery, treated with =2 systemic treatments, were included. Four main therapeutic sequences were identified in 99 patients: (A) somatostatin analogs (SSA) standard dose to SSA high dose (n?=?36), (B) SSA to everolimus (n?=?31), (C) SSA to chemotherapy (n?=?17), (D) SSA to peptide receptor radionuclide therapy (PRRT) (n?=?15). Median PFS of the second-line treatment was not reached in sequence A, 33 months in sequence B, 20 months in sequence C, 30 months in sequence D (p?=?0.16). Both total number and severity of side effects were significantly higher in sequences B and C than A and D (p?=?0.04), as well as the rate of dose reduction/discontinuation (p?=?0.03). Conclusions: SSA followed by SSA high dose, everolimus, chemotherapy or PRRT represent the main therapeutic sequences in G1-G2 NET. Median PFS was not significantly different between sequences. However, the sequences with SSA high dose or PRRT seem to be better tolerated than sequences with everolimus or chemotherapy.

Patients with advanced or recurrent thymic epithelial tumors (TETs) often need several consecutive lines of chemotherapy. The aim of this retrospective monocentric study was to test whether 18F-Fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) is able to monitor standard chemotherapy efficacy in those patients and whether metabolic response correlates with morphovolumetric response as assessed by Response Evaluation Criteria in Solid Tumor (RECIST). We evaluated 27 consecutive patients with advanced (16 patients) or recurrent (11 patients) TETs. All patients underwent 18F-FDG PET-CT before and after at least 3 cycles of chemotherapy. Maximum standardized uptake value (SUVmax) of all detected lesions was recorded and the most 18F-FDG avid lesion in each patient was selected for determination of percentage change of SUVmax(ΔSUVmax) in pre- and post-treatment scans. Tumor response was assessed by contrast-enhanced computed tomography (CE-CT) using RECIST criteria. Receiver operating characteristic (ROC) curve analysis was performed to define the optimal threshold of ΔSUVmaxdiscriminating responders from non-responders. Metabolic response expressed as ΔSUVmaxwas significantly correlated with morphovolumetric response (Spearman’s rank correlation, r= 0.64, p= 0.001). ROC curve analysis showed that a ΔSUVmaxvalue of -25% could discriminate responders from non-responders with a sensitivity of 88% and a specificity of 80%. Conversely, basal SUVmaxvalues were not predictive of morphovolumetric tumor response. Our findings indicate that metabolic response assessed by 18F-FDG PET-CT, through evaluation of ΔSUVmax, may allow identification of responders and non-responders thus guiding adaptation of therapy in patients with advanced or recurrent TETs.

Tumor-to-tumor metastasis is a rare phenomenon, with around 150 cases being reported in the literature. Breast cancer is the second most commonly reported donor tumor after lung cancer, but thymic epithelial tumors have never been reported as recipient tumors. Furthermore, the thymus is rarely affected by metastases. To our knowledge, the present report is the first case of breast cancer metastatic to thymic epithelial tumor.

To determine the impact of prophylaxis with granulocyte-colony stimulating growth factor (G-CSF) on the risk of febrile neutropenia in a cohort of patients enrolled at the University Federico II of Naples and treated with cabazitaxel for metastatic castration-resistant prostate cancer (mCRPC). We carried out a retrospective review of prospectively collected data of patients enrolled at our institution in a compassionate-use programme with cabazitaxel, aimed at providing early access to the drug before its commercial availability in mCRPC patients. Besides baseline clinical and demographic characteristics, data on treatment efficacy and toxicity, as well as those on the use of G-CSF per patient per cycle were extracted. Progression-free survival and overall survival were calculated using the Kaplan–Meier method. Fisher’s exact test was used to explore a relationship between a single event of grade 3 or more neutropenia or febrile neutropenia and previous use of G-CSF. Univariate analysis was carried out to evaluate predictors of grade 3 or more neutropenia andor febrile neutropenia. Of 34 patients enrolled at our institution from December 2010 to December 2011, 32 had received at least one dose of cabazitaxel and were included in the analysis. Patients received a median of 10 cabazitaxel cycles. Grade 3 or more neutropenia was common, occurring in 64.5 of patients. Three patients (9.3) developed febrile neutropenia. Twenty-seven patients received prophylaxis with G-CSF during at least one cycle using peg-filgrastim. The risk of grade 3 or more neutropenia andor febrile neutropenia per patient and per cycle was seven times lower when G-CSF was used. Baseline neutrophil count of less than 4570mm3was the strongest predictor of grade 3 or more neutropenia andor febrile neutropenia. No toxic death was reported. Only one patient discontinued cabazitaxel because of an adverse event. Our analysis suggests that prophylaxis with peg-filgrastim may considerably reduce the incidence of grade 3 or more neutropenia and, possibly, of febrile neutropenia in mCRPC patients treated with cabazitaxel. Further analyses involving a larger population are warranted to confirm our results.

Guidelines on the treatment of metastatic squamous cell carcinoma of the penis are limited to a few prospective trials. Cisplatin-based regimens represent the standard of treatment with promising activity of taxanes. Recently, epidermal growth factor receptor overexpression has been shown in these patients. We treated an elderly man with a docetaxel–cetuximab combination after failure of the cisplatin regimen. We observed a necrosis of the inguinal lymph nodes and a reduction of 18F-fluorodeoxyglucose uptake at PETCT scan. Only mild mucositis and skin toxicity had been detected. Our case report, the first in the literature, shows that this combination is active and well tolerated in penile squamous cell carcinoma.

Germ cell tumors are rare neoplasms that affect young males. Nearly 99% of patients with localized stage I disease and nearly 80% of patients with metastatic disease can be cured. Even patients who relapse following chemotherapy can achieve a long-term survival in approximately 30–40% of cases. The main objective in early stages and in good prognosis patients has changed in recent years, and it has become of major importance to reduce treatment-related morbidity without compromising the excellent long-term survival rate. In poor prognosis patients, there is a correlation between the experience of the treating institution and the long-term clinical outcome of the patients, particularly when the most sophisticated therapies are needed. So far, of utmost importance is the information from updated practice guidelines for the diagnosis and treatment of germ cell tumors. The Italian Germ cell cancer Group (IGG) has developed the following clinical recommendations, which identify the current standards in diagnosis and treatment of germ cell tumors in adult males.

Therapeutic options to cure advanced, recurrent, and metastatic thymic tumors are limited. Evidence of a high uptake of indium-labeled octreotide (¹¹¹In-DTPA-D-Phe¹-octreotide) in thymic tumors and the curative application of somatostatin analogs and prednisone in one patient with thymoma and pure red cell aplasia led the authors to start a Phase II study. Sixteen patients with advanced thymic tumors, unresponsive to conventional chemotherapeutic regimens, were enrolled in the study. The schedule includes administration of somatostatin analog octreotide (1.5 mg/day subcutaneously) associated with prednisone (0.6 mg/kg/day orally for 3 months, 0.2 mg/kg/day orally during follow-up). In 8 cases, octreotide was replaced by the long-acting analog lanreotide (30 mg/every 14 days intramuscolarly). Treatment was prolonged until progression of disease was documented. Overall response rate, survival, progression free survival, and toxicity were evaluated. The overall response rate among 16 evaluable patients was 37%. One patient (6%) had a complete response, 5 (31%) had a partial response, 6 obtained a stabilization of disease, and 4 progressed during the treatment. After a median follow-up of 43 months, the median survival was 15 months, and median time to progression was 14 months. Treatment was generally well tolerated with acceptable toxicity: cholelithiasis (1 patient), Grade 2 cushingoid appearance (3 patients), Grade 1 diarrhea (5 patients), Grade 2 hyperglycemia (3 patients). Treatment with somatostatin analogs and prednisone has shown efficacy in patients with recurrent and metastatic malignant thymic tumors refractory to standard therapeutic options. The results obtained are very satisfactory given the lack of effective alternative treatments. Such therapy is not burdened by the same toxicity of chemotherapy; thus, it can be administered to heavily pretreated patients. Somatostatin analogs and prednisone are well tolerated, and the long-acting analog lanreotide, which requires fewer injections, improves patients' compliance. Cancer 2002;94:1414–20. © 2002 American Cancer Society. DOI 10.1002/cncr.10374

Langerhans cell histiocytosis is a rare group of diseases of unknown pathogenesis, variable clinical presentation, and behavior. It encompasses highly aggressive, often fatal, and indolent diseases, with a variety of intermediate forms between the two extremes. Localization and monitoring of Langerhans cell histiocytosis deposits are based on the combined use of different imaging modalities, which include magnetic resonance, computed tomography, and nuclear medicine procedures. Somatostatin receptor scintigraphy recently has been used to image immune-mediated diseases with excellent results. In this study, the authors have evaluated the potential role of somatostatin receptor scintigraphy by using ¹¹¹In-DTPA-D-Phe¹-octreotide in a series of patients with Langerhans cell histiocytosis. Eight consecutive patients (2 males, 6 females; mean age, 43 years; age range, 29–60 years) with histologically proven Langerhans cell histiocytosis, in various phases of their disease, were imaged 24 hours after intravenous injection of 111–222 MBq of ¹¹¹In-DTPA-D-Phe¹-octreotide, by using total body and spot view images. The objective of the study was to preliminarly evaluate this technique in the evaluation of Langerhans cell histiocytosis. Most Langerhans cell histiocytosis deposits were clearly documented by somatostatin receptor scintigraphy, independently from the anatomic location (i.e., skeleton, mucosae, soft tissue, etc.). The correlation between conventional imaging modalities and somatostatin receptor scintigraphy results was fairly good, though this was not considered a primary objective of the study. Among the various imaging modalities for Langerhans cell histiocytosis, somatostatin receptor scintigraphy is unique, becuase it accurately depicts the active sites of disease and thus can help in monitoring the response to treatment, together with conventional imaging modalities. Further studies are necessary to confirm the diagnostic value of this technique and clarify the biologic significance of the expression of somatostatin receptors in Langerhans cell histiocytosis. Cancer 2002;94:633–40. © 2002 American Cancer Society. DOI 10.1002/cncr.10276

Summary Human melanoma cells are sensitive to the lytic activity of natural killer (NK) and lymphokine-activated killer (LAK) cells in vitro. The events resulting in tumour cell killing by lymphocytic effectors have not been completely clarified, and the same target cell determinants regulating responsiveness to immune cytolysis have not yet been identified. Indeed, changes in the differentiative status of leukemia cells as well as in the expression of major histocompatibility complex (MHC) antigens have been described to modulate sensitivity to cytotoxic effectors; moreover surface expression of adhesion factors or extracellular matrix proteins by the cancer cells can promote the activation of the cytolytic effectors and has been described to correlate with tumour cell sensitivity to cytolytic cells. We reasoned that treatment with differentiation inducers could modulate melanoma cell sensitivity to NK and LAK cells. The present study demonstrates that human melanoma GLL-19 cells, when treated with the phorbol diester phorbol 12-myristate 13-acetate (PMA) in vitro, undergo growth inhibition and neuron-like differentiation. Moreover PMA treatment induces an evident inhibition of GLL-19 cell sensitivity to NK- and LAK-mediated cytotoxicity. GLL-19 cells express constitutively MHC class I antigens. PMA treatment, however, does not modify the expression of MHC class I and class II DR antigens in human melanoma GLL-19 cells. We have finally evaluated the effects of PMA on the expression at the cell surface of adhesion factors such as ICAM-1, and extracellular matrix proteins such as collagen IV, laminin and fibronectin; we have also studied the expression of the integrin vitronectin receptor, a membrane receptor for adhesive proteins. While adhesion factors and extracellular matrix proteins appear to play an important role in the interaction between immune effector and tumour target, it can be supposed that the modulation of such membrane-associated proteins or glycoproteins induces NK and LAK resistance in cancer cells. We indeed found that PMA treatment induced in GLL-19 a marked reduction of membrane expression of collagen IV and ICAM-1; moreover PMA reduced the cell membrane expression of the integrin vitronectin receptor. On the other hand, membrane expression of fibronectin and laminin was not affected by PMA. These data indicate that the acquisition of a NK- and LAK-resistant phenotype by GLL-19 cells occurs together with cell differentiation, down-regulation of membrane expression of collagen IV, ICAM-1 and vitronectin receptor, but in the absence of changes in MHC antigens.

We report our experience in the treatment of pleural effusion in 25 patients with metastatic breast cancer. Seventeen patients received initial systemic therapy and in 13 of them local intrapleural therapy was subsequently employed; the remaining 8 patients received local therapy only. Several modalities of local treatment were used: intrapleural chemotherapy with thiotepa and 5-fluorouracil; the production of pleural adhesion by the use of chest drainage alone or associated with instillation of sclerosing agents, such as nitrogen mustard or tetracycline. Of the 21 patients who were subjected to local therapy, 19 (90.5%) achieved an objective response (16 complete (76.2%) and 3 (14.34%) partial). Complete responses were observed exclusively in patients who had pleurodesis. Our data suggest that pleurodesis is the treatment of choice for neoplastic pleural effusion and that the use of tetracycline as a sclerosing agent is the most useful because of its availability, low cost and low morbidity.

Denosumab has been proven to be at least as effective with respect to zoledronic acid in preventing skeletal-related events in patients with bone metastases from solid tumors. Although denosumab can be considered to have a more favorable toxicity profile compared to zoledronic acid in terms of kidney toxicity and flu-like symptoms, hypocalcemia is twice as frequent with denosumab. Importantly, denosumab is not metabolized by the kidney and it may be employed even in patients with severe kidney failure. Like zoledronic acid, denosumab is administered with oral calcium and vitamin D. As conversion of vitamin D to its active form is progressively impaired with a creatinine clearance < 70 ml/min, we speculate that calcitriol may be a better option than vitamin D in denosumab-treated patients with impaired kidney function.

BACKGROUND Good syndrome (GS) refers to a constellation of thymoma and adult-onset immunodeficiency characterized by low or absent B cells, hypogammaglobulinemia, and variable defects in cell-mediated immunity with an inverted CD4/CD8+ T-cell ratio. Patients may develop severe or chronic infections as a result of this immunodeficiency. OBJECTIVE To describe a patient with GS who developed cytomegalovirus (CMV) encephalitis and showed a periodic electroencephalographic pattern and myoclonus. DESIGN Case report. SETTING Outpatient neurology clinic at a university medical center. PATIENT A 64-year-old man who developed periodic myoclonus involving the right half of his body and the left arm. RESULTS Five years previously, the patient had undergone resection of a pathologically confirmed epithelial thymoma. Quantitative CMV polymerase chain reaction of the serum and cerebrospinal fluid showed strongly positive results (1:10 000), allowing the diagnosis of CMV encephalitis. CONCLUSIONS To the best of our knowledge, myoclonus and periodic electroencephalographic pattern have not previously been reported in CMV encephalitis. Opportunistic CMV infection should be considered early in the evaluation of patients with GS or a history of thymoma who develop unusual neurological symptoms.Arch Neurol. 2007;64:277-279 --

Thymoma is a rare tumor characterized by an association with autoimmune diseases. Immunological abnormalities are increasingly being recognized in thymoma patients and are the cause of a peculiar susceptibility to infections. The authors present the clinical history of a thymoma patient affected by fatal immunodeficiency.

A subgroup of thymoma patients is affected by severe immunodeficiency clinically resembling an HIV infection (Good syndrome). These individuals are characterized by B lymphopenia with B-lymphopoiesis deficiency. To investigate the pathogenesis of this unique condition, we studied the T-cell repertoire in blood and bone marrow samples by heterogeneity length analysis of CDR3 beta variable regions of the T-cell receptor (spectratyping). While no alterations were found in the peripheral blood, we detected an oligoclonal population of β variable 8 (BV8) CD8+T cells in 5 of 5 bone marrow samples. No lymphocyte expansions were found in the bone marrow of 2 thymoma patients with normal B-cell counts, 2 healthy donors, and 3 patients with diseases unrelated to thymoma. These data suggest that an immune response toward an unknown antigen is taking place in the bone marrow of B-lymphopenic thymoma patients. We propose that BV8 CD8+T cells may play a role in the pathogenesis of this immunodeficiency syndrome.

A subgroup of thymoma patients is affected by severe immunodeficiency clinically resembling an HIV infection (Good syndrome). These individuals are characterized by B lymphopenia with B-lymphopoiesis deficiency. To investigate the pathogenesis of this unique condition, we studied the T-cell repertoire in blood and bone marrow samples by heterogeneity length analysis of CDR3 beta variable regions of the T-cell receptor (spectratyping). While no alterations were found in the peripheral blood, we detected an oligoclonal population of β variable 8 (BV8) CD8+ T cells in 5 of 5 bone marrow samples. No lymphocyte expansions were found in the bone marrow of 2 thymoma patients with normal B-cell counts, 2 healthy donors, and 3 patients with diseases unrelated to thymoma. These data suggest that an immune response toward an unknown antigen is taking place in the bone marrow of B-lymphopenic thymoma patients. We propose that BV8 CD8+ T cells may play a role in the pathogenesis of this immunodeficiency syndrome.

We describe a case of partial regression of metastatic hepatocellular carcinoma after treatment with thymostimulin. The patient, a 58-year-old man, received no specific therapy for his tumor, but only a thymus extract (« thymostimulin »). At follow-up 6 months later the patient showed clinical improvement, reduction of alpha-fetoprotein level an liver lesions, and a complete regression of lung metastases. The patient died of progression of the disease with 2-year overall survival.

A total of 72 patients with metastatic stage IV non-small-cell lung cancer (NSCLC) were treated with combination chemotherapy comprising the MEV regimen (mitomycin C, 8 mg/m2 given i. v. on day 1; etoposide, 100 mg/m2 given i.v. on days 1–3; and vindesine, 3 mg/m2 given i.v. on day 1; treatment repeated every 3 weeks). In 64 evaluable patients, the objective response rate was 37% (complete responses, 4.7%; partial responses, 32.3%). The median survival was 7.6 months for all patients. The treatment was very well tolerated. MEV proved to be an active and non-toxic regimen for the treatment of metastatic NSCLC.

We report the case of an 82-year old Italian female with laryngeal involvement of classic Kaposi's sarcoma. We obtained a complete regression of laryngeal lesion with low-dose alpha-2b interferon.

A case is reported of a 76 year old patient with inoperable lymph node metastases from cancer of the penis. Methotrexate and bleomycin chemotherapy and concurrent irradiation were administered. The patient achieved a complete remission and is disease-free 30 months after therapy. The treatment was well tolerated.

On the basis of promising results obtained by imatinib mesilate in a patient with cerebral LCH with high expression of PDGFRb in the affected tissue (Case Report in press in the New Engl J Med), we evaluated PDGFRb expression by immunohistochemistry on banked LCH specimens. Methods: A 4 m m section obtained from formalin-fixed, paraffin-embedded specimens was incubated in a microwave oven for 15 min in 10 mmol/L buffered citrate pH 6.0, followed by immunohistochemical procedures to detect PDGFRb (using a rabbit polyclonal antibody, Santa Cruz Biotechnology Inc., CA) and KIT (CD117, Dako, Carpinteria, CA), diluted 1:50 and 1:300, respectively. A conventional avidin-biotin complex procedure was then applied, according to manufacturer’s protocol. Briefly, the sections were washed and incubated with the primary antibody overnight at 4°C, then incubated with the secondary antibody. Positive staining was revealed by the DAB chromogen, followed by counterstaining with Mayer’s hematoxilin. The slide was cover-slipped with a xilene-based mounting medium. The staining was scored as Neg, +1 (low expression), +2 (intermediate expression), or +3 (strong expression). Results. Up to now, we have analysed specimens from 9 patients (see Table). A strong PDGFRb expression with a predominant cytoplasmic localization was detected in 5 cases; two specimens had intermediate expression and two low expression. KIT expression was never observed. The study is ongoing, to evaluate a larger number of cases; however, in the limited series presented, 70% of cases had a significant PDGFRb expression. This finding may stimulate further clinical investigation on the use of tirosin kinase inhibitors in LCH. PDGFRß and KIT expression in LCH specimens Case Gender/Age Disease site KIT PDGFRß C: cytoplasmic; N: nuclear 1 M/10 ocular soft tissue Neg +1C 2 F/9 skin Neg +3C/N 3 M/76 skin Neg +2C 4 M/13 bone Neg +3C 5 M/19 bone Neg +3C 6 M/1 bone Neg +1C 7 M/45 oral mucosa Neg +3C 8 F/23 brain Neg +2C 9 M/45 oral mucosa Neg +3C

On the basis of promising results obtained by imatinib mesilate in a patient with cerebral LCH with high expression of PDGFRb in the affected tissue (Case Report in press in the New Engl J Med), we evaluated PDGFRb expression by immunohistochemistry on banked LCH specimens.