Diffuse panbronchiolitis in a patient with common variable immunodeficiency: a casual association or a pathogenetic correlation?

Diffuse panbronchiolitis (DPB) is an idiopathic inflammatory disease that seems to have an immunological pathogenesis and that causes a severe progressive suppurative and obstructive respiratory disorder. Common variable immunodeficiency (CVID) is the most common serious primary immunodeficiency and it is often associated with respiratory diseases. Herein, we describe a case of DPB in a 41-year-old man affected by CVID. We examined the patient's lungs, focusing on the characteristics of the inflammatory cells and of the foamy macrophagic nodules typical of DPB. Immunohistochemical typing of the lymphocytic infiltrate showed that B-cells were almost absent, matching the immunological profile of CVID. The case described is the first case reported in the literature of DPB in a patient affected by CVID. Moreover it seems to confirm the correlation between an immunodeficiency status and the development of DPB and provides more information on the accumulation of nodules of foamy macrophages in DPB

Correlation between MYC gene rearrangement and MYC protein expression suggests that MYC regulation is more complex than previously known

Since its discovery in the 1970's, MYC oncoprotein has been continuing to fascinate the scientific world and there is a growing interest in the role of MYC in the genesis and prognosis of cancer. Initially MYC was identified as the cellular homologue of the MC29 transforming avian retrovirus. Shortly hereafter, additional related sequences were identified, suggesting that MYC might be part of a larger family of genes. The constellation of MYC effects on genes involved in proliferation has led to the concept of MYC-driven lymphomas, that include Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), and lymphomas that share morphologic features of DLBCL and BL, officially termed B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL (BCLU). Other lymphomas showing MYC over-expression comprises Plasmablastic lymphoma and Plasmacytoma, Double hit/triple hit lymphomas and Anaplastic lymphomas Kinase-positive Large B-cell Lymphoma. MYC aberrations can be detected by standard cytogenetics, interphase fluorescence in situ hybridization (FISH), comparative genomic hybridization and most recently immunohistochemistry. By comparing expression profiles of MYC gene rearrangement and MYC protein expression has came up that MYC gene rearrangements do not necessarily correlate with MYC protein expression. In fact, by applying immunoistochemistry, the frequency of MYC protein expression appears much higher than what is detected by FISH standard method. Therefore, nowadays the key problem in the hematopathology field is to define the clinical impact of the double-expressor lymphoma status. The updated World Health Organization (WHO) of tumours of hematopoietic and lymphoid tissues asses that the status of double or triple lymphoma should rely only on molecular biology findings and not on immunohistochemistry results

Translationally controlled tumor protein in prostatic adenocarcinoma: correlation with tumor grading and treatment-related changes

12Prostate cancer is the second leading cause of cancer-related death. The androgen deprivation therapy is the standard treatment for advanced stages. Unfortunately, virtually all tumors become resistant to androgen withdrawal. The progression to castration-resistance is not fully understood, although a recent paper has suggested translationally controlled tumor protein to be implicated in the process. The present study was designed to investigate the role of this protein in prostate cancer, focusing on the correlation between its expression level with tumor differentiation and response to treatment. We retrieved 292 prostatic cancer specimens; of these 153 had been treated only by radical prostatectomy and 139 had undergone radical prostatectomy after neoadjuvant treatment with combined androgen blockade therapy. Non-neoplastic controls were represented by 102 prostatic peripheral zone specimens. In untreated patients, the expression of the protein, evaluated by RT-qPCR and immunohistochemistry, was significantly higher in tumor specimens than in non-neoplastic control, increasing as Gleason pattern and score progressed. In treated prostates, the staining was correlated with the response to treatment. An association between protein expression and the main clinicopathological factors involved in prostate cancer aggressiveness was identified. These findings suggest that the protein may be a promising prognostic factor and a target for therapy.openopenRocca, Bruno Jim; Ginori, Alessandro; Barone, Aurora; Calandra, Calogera; Crivelli, Filippo; De Falco, Giulia; Gazaneo, Sara; Tripodi, Sergio; Cevenini, Gabriele; Del Vecchio, Maria Teresa; Ambrosio, Maria Raffaella; Tosi, PieroRocca, BRUNO JIM; Ginori, Alessandro; Barone, Aurora; Calandra, Calogera; Crivelli, Filippo; DE FALCO, Giulia; Gazaneo, Sara; Tripodi, Sergio; Cevenini, Gabriele; DEL VECCHIO, MARIA TERESA; Ambrosio, MARIA RAFFAELLA; Tosi, Pier

Defective IGF-1 prohormone N-glycosylation and reduced IGF-1 receptor signaling activation in congenital disorders of glycosylation

none14sìThe insulin-like growth factor-1 (IGF-1) signaling pathway is crucial for the regulation of growth and development. The correct processing of the IGF-1Ea prohormone (proIGF-1Ea) and the IGF-1 receptor (IGF-1R) peptide precursor requires proper N-glycosylation. Deficiencies of N-linked glycosylation lead to a clinically heterogeneous group of inherited diseases called Congenital Disorders of Glycosylation (CDG). The impact of N-glycosylation defects on IGF-1/IGF-1R signaling components is largely unknown. In this study, using dermal fibroblasts from patients with different CDG [PMM2-CDG (n = 7); ALG3-CDG (n = 2); ALG8-CDG (n = 1); GMPPB-CDG (n = 1)], we analyzed the glycosylation pattern of the proIGF-1Ea, IGF-1 secretion efficiency and IGF-1R signaling activity. ALG3-CDG, ALG8-CDG, GMPPB-CDG and some PMM2-CDG fibroblasts showed hypoglycosylation of the proIGF-1Ea and lower IGF-1 secretion when compared with control (CTR). Lower IGF-1 serum concentration was observed in ALG3-CDG, ALG8-CDG and in some patients with PMM2-CDG, supporting our in vitro data. Furthermore, reduced IGF-1R expression level was observed in ALG3-CDG, ALG8-CDG and in some PMM2-CDG fibroblasts. IGF-1-induced IGF-1R activation was lower in most PMM2-CDG fibroblasts and was associated with decreased ERK1/2 phosphorylation as compared to CTR. In general, CDG fibroblasts showed a slight upregulation of Endoplasmic Reticulum (ER) stress genes compared with CTR, uncovering mild ER stress in CDG cells. ER-stress-related gene expression negatively correlated with fibroblasts IGF-1 secretion. This study provides new evidence of a direct link between N-glycosylation defects found in CDG and the impairment of IGF-1/IGF-1R signaling components. Further studies are warranted to determine the clinical consequences of reduced systemic IGF-1 availability and local activity in patients with CDG.openDi Patria, Laura; Annibalini, Giosuè; Morrone, Amelia; Ferri, Lorenzo; Saltarelli, Roberta; Galluzzi, Luca; Diotallevi, Aurora; Bocconcelli, Matteo; Donati, Maria Alice; Barone, Rita; Guerrini, Renzo; Jaeken, Jaak; Stocchi, Vilberto; Barbieri, ElenaDi Patria, Laura; Annibalini, Giosuè; Morrone, Amelia; Ferri, Lorenzo; Saltarelli, Roberta; Galluzzi, Luca; Diotallevi, Aurora; Bocconcelli, Matteo; Donati, Maria Alice; Barone, Rita; Guerrini, Renzo; Jaeken, Jaak; Stocchi, Vilberto; Barbieri, Elen

CT Perfusion in the Characterisation of Renal Lesions: An Added Value to Multiphasic CT

Objective. To prospectively evaluate if computed tomography perfusion (CTp) could be a useful tool in addition to multiphasic CT in renal lesion characterisation. Materials and Methods. Fifty-eight patients that were scheduled for surgical resection of a renal mass with a suspicion of renal cell carcinoma (RCC) were enrolled. Forty-one out of 58 patients underwent total or partial nephrectomy after CTp examination, and a pathological analysis was obtained for a total of 49 renal lesions. Perfusion parameters and attenuation values at multiphasic CT for both lesion and normal cortex were analysed. All the results were compared with the histological data obtained following surgery. Results. PS and MTT values were significantly lower in malignant lesions than in the normal cortex (P < 0.001 and P = 0.011, resp.); PS, MTT, and BF values were also statistically different between oncocytomas and malignant lesions. According to ROC analysis, the accuracy, sensitivity, and specificity to predict RCC were 95.92%, 100%, and 66.7%, respectively, for CTp whereas they were 89.80%, 93.35%, and 50%, respectively, for multiphasic CT. Conclusion. A significant difference between renal cortex and tumour CTp parameter values may suggest a malignant renal lesion. CTp could represent an added value to multiphasic CT in differentiating renal cells carcinoma from oncocytoma

Benign ulcer of the right colon clinically misdiagnosed as carcinoma: an additional case

Benign solitary ulcer of the colon is an uncommon lesion that was originally described by Cruveilhier in 1832. Its aetiology remains unknown, and there are no pathognomonic lesions or symptoms. Diagnosis is made by exclusion; in fact, diseases such as specific infections (cytomegalovirus, campylobacter jejuni, entamoeba histolytica), common clinical conditions (acute appendicitis, diverticulitis, intestinal obstruction, inflammatory bowel disease), pharmacotherapy (non-steroidal anti-inflammatory medications, oral contraceptives, dicumarolic agents) and malignancies should be excluded. We describe the case of a 72-year-old patient admitted for acute bloody diarrhoea, originally misdiagnosed as carcinoma by colonscopy. The histological evaluation demonstrated a benign ulcerative lesion

Primary anorectal Hodgkin lymphoma: report of a case and review of the literature.

7noreservedPrimary colorectal lymphomas are very rare. They are mostly B-cell non-Hodgkin lymphomas. Only 2 cases of anorectal Hodgkin lymphoma have been described so far, both affecting HIV-infected males and showing Epstein-Barr virus infection. We report an unusual case of primary Hodgkin lymphoma of the anorectal region in an HIV-negative, Epstein-Barr virus-infected patient and in the absence of inflammatory bowel disease. The importance of distinguishing Hodgkin lymphoma from Epstein-Barr virus-induced lymphoproliferative disorders and from Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly is stressed in particular in non-immunocompromised patients and in the absence of history of inflammatory bowel disease.mixedAmbrosio, MARIA RAFFAELLA; Rocca, BRUNO JIM; Barone, Aurora; Mastrogiulio, MARIA GRAZIA; Costa, A.; Bellan, Cristiana; Lazzi, StefanoAmbrosio, MARIA RAFFAELLA; Rocca, BRUNO JIM; Barone, Aurora; Mastrogiulio, MARIA GRAZIA; Costa, A.; Bellan, Cristiana; Lazzi, Stefan

Unusual clear cell, lymphoplasmacyte-rich, dural-based tumor with divergent differentiation: A tricky case mimicking a meningioma

We describe an unusual case of a recurrent dural neoplasm, previously diagnosed as meningioma. Histopathologically, the tumor is characterized by aggregates of divergently differentiated clear cells embedded in an abundant lymphoplasmacyte-rich stroma, mimicking a lymphoplasmacyte-rich meningioma. This study focuses on the histologic and immunohistochemical characterization of a unique dural-based tumor and provides useful guidelines for differentiating meningioma from other uncommon dural-based neoplasms. We propose that this recurrent dural neoplasm is a distinctive entity and, therefore, enlarges the spectrum of dural-based neoplasms that enter the differential diagnosis with meningiomas. Awareness of this tumor entity could prove useful for appropriate patient management