PATTERN OF A PRIMARY B-CELL LYMPHOMA IN ULNAR NERVE: INTRANEURAL OR EXTRANEURAL.

Primary lymphomas of peripheral nerves (PLPNs) are extremely rare and most commonly reported in lumbar nerves and have been found in only five cases in the upper extremities. We describe two patterns of presentation focusing on clinical, radiological, and pathological findings of two patients affected by primary multifocal lymphoma of the ulnar nerve without systemic involvement or other medical conditions. We report a case of extraneural lymphoma in a 72-years-old (patient #1) and a case of intraneural lymphoma in a 45-years old woman (Patient #2). Magnetic resonance imaging and ultrasound findings were similar to Peripheral Nerve Sheath Tumors (PNST). Surgical exploration and excision were performed. Morpho pathological results revealed in both cases a diffuse large B-cell non-Hodgkin lymphoma. In patient #1, the disease relapsed after only 4 months with brachial plexus involvement. The patient died about 10 months after the onset of symptoms. Patient #2 did not have post-surgical sensory or motor deficit and follow up at 6 years did not show recurrence or any other localizations. PLPN is a rare and challenging condition and is frequently misdiagnosed. PLPNs could have an intraneural or an extraneural pattern. As peripheral neuropathy may be caused by a nervous involvement by a lymphoma, in patients with atypical lesions, a complete preoperative imaging should be acquired.

Case report: Dupilumab treatment improved type 2 disorders in a patient with IPEX syndrome diagnosis.

We described a case of IPEX syndrome successfully controlled with dupilumab, an anti-IL4 receptor alpha subunit inhibitor. IPEX syndrome is a rare and generally fatal genetic disorder characterized by immune dysregulation, polyendocrinopathy and enteropathy, mostly diagnosed in early childhood. Nonetheless, cases reported in the last 20 years demonstrated that IPEX clinical spectrum encompasses more than the classical triad of early-onset intractable diarrhea, type 1 diabetes and eczema. Atypical cases of IPEX include patients with late-onset of symptoms, single-organ involvement, mild disease phenotypes or rare clinical features. A 21-year-old caucasian man presented with immune dysregulation (hypereosinophilia and elevated IgE), protein-losing enteropathy, polyendocrinopathy (thyroiditis, osteoporosis, delayed puberty), weight loss, eczema manifestations and celiac disease. IPEX syndrome was diagnosed because of the presence of a hemizygous mutation in FOXP3 gene (c.543C>T (p.S181S) in the exon 5). During the course of the disease, the patient developed erosive proctitis, pyoderma gangrenosum, and erythema nodosum. Symptoms improved only after enteral and parenteral corticosteroid therapy and the patient soon developed steroid-dependence. Notwithstanding various therapies including azathioprine, sirolimus, tacrolimus, adalimumab, vedolizumab, the patient failed to achieve a good control of symptoms without steroids. Almost exclusive enteral nutrition with a hypoallergenic, milk-protein free, amino acid-based food for special medical purposes. He continued to lose weight (BMI 14.5 kg/m2) with a consequent high limitation of physical activity and a progressive worsening of the quality of life. In consideration of the poor response to conventional immunosuppressants and the presence of type 2 inflammatory manifestations, treatment with dupilumab at an initial dose of 600 mg, followed by a maintenance dose of 300 mg every other week, according to atopic dermatitis labeled dose, was started and combined to oral budesonide 6 mg/day and 6-mercaptopurine 75 mg/day. The patient experienced a rapid improvement in bowel and skin symptoms, leading to a progressive tapering of steroids. By our knowledge, this is the first report of IPEX syndrome successfully treated by antiIL-4/IL-13 therapy. In this case dupilumab demonstrated to be an effective, safe and steroid-sparing option.

The effects of collagenase of Clostridium Histolitycum (CCH) in Dupuytren's disease: a histological study on cell mediated mechanisms that allow enzymatic fasciotomy.

Dupuytren Disease is a benign fibromatosis of palmar fascia of the hand, whose pathophysiology is not completely understood. The present study is intended to provide a description of the effects of Collagenase of Clostridium Hystoliticum (CCH) into an injected cord of Dupuytren. Our experimental study wanted to evaluate the histological effects of injection of CCH in the first 24 hours, without manipulating the specimens. MATERIALS AND METHODS: Surgical specimens were injected with CCH, and then fixed in formalin every six hours, up to 24 hours. Those specimens were compared to control specimen (non-injected), fixed and analyzed at the same times. RESULTS: In the injected specimens, the number of CD68 positive cells increased into and outside the cords compared to non injected specimens, within the same time from the surgical removal. CONCLUSION: CCH has a proinflammatory activity and provokes a short ray chemotactic action on white blood cells. The lysis of the cord induced by CCH stimulates the inflammatory response. The role of the inflammatory infiltration deserves to be investigated in a more accurate way, preferably by using in vivo studies.

Severe eosinophilic asthma and aspirin-exacerbated respiratory disease associated to eosinophilic gastroenteritis treated with mepolizumab: a case report.

BACKGROUND: Mepolizumab (MEP) is the first anti Interleukin (IL)-5 add-on therapy approved for the treatment of severe refractory eosinophilic asthma. CASE PRESENTATION: We describe here the case of a 49 years-old woman with Aspirin-exacerbated respiratory disease (AERD), chronic rhinosinusitis, nasal polyposis and eosinophilic gastroenteritis successfully treated with MEP. Several laboratory and clinical items improved during therapy; moreover MEP showed to be useful as steroid sparing agent. CONCLUSIONS: This case supports that the use of mepolizumab can be effective also in other eosinophilic conditions different from asthma and this opens to new therapeutic perspectives.

Laparoscopic approach for a presacral myelolipoma resembling a liposarcoma.

Myelolipomas are rare benign tumors that are commonly found in the adrenal glands. Extra-adrenal locations are rare, and presacral myelolipomas represent the most common extra-adrenal location. The differential diagnosis of malignant presacral neoplasms is very challenging. We present a case of a presacral neoplasm that was completely removed with a laparoscopic approach and diagnosed as a myelolipoma only after pathological examination.

Systematic review of the literature and a case report informing biopsy-proven giant cell arteritis (GCA) with normal C-reactive protein.

Giant cell arteritis (GCA) is a vasculitis of large- vessels. A markedly elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels are characteristics of GCA, although temporal artery biopsy remains the gold standard for the diagnosis. We describe a case of biopsy-proven GCA showing a heavy infiltration of CD68 macrophages and CD3 T cells and with normal ESR and CRP levels at diagnosis. Key points (1) GCA may occur with normal ESR in a percentage of about 4 to 15 % (although the American College of Rheumatology classification criteria for giant cell arteritis include an ESR of 50 mm/h or more), while it can occur with normal ESR and normal CRP in a percentage of about 0.8 %. So, the clinical suspicion must be confirmed with a positive biopsy. (2) GCA patients with ESR >40 mm/h are characterized by higher incidence of headache and jaw claudication compared to patients with normal ESR. In our case, it occurred with normal ESR. (3) Color duplex ultrasonography is a noninvasive, easy, and inexpensive method for supporting a diagnosis of TA, with a high sensitivity and specificity. It can predict which patient will need TAB.

Promyelocytic leukemia (PML) gene expression is a prognostic factor in ampullary cancer patients.

BACKGROUND: Promyelocytic leukemia (PML) tumor suppressor gene plays a key role in acute PML pathogenesis but its involvement in pathogenesis and prognosis of solid cancers has not been defined yet. PATIENTS AND METHODS: In all, 62 ampullary adenocarcinoma patients who underwent curative surgery between 1996 and 2005 were included. Expression analysis of PML was carried out by immunohistochemical staining and correlated with disease-free survival (DFS) and overall survival (OS). RESULTS: In 24 tumor specimens (38.7%), PML was classified as absent, in 16 (25.8%) as focally expressed and in 22 (35.5%) as diffusely expressed. By univariate analysis, DFS was significantly influenced by pathological T stage (P=0.03), lymph nodal involvement (P=0.002), and PML expression (P=0.001). DFS in patients without PML expression was 28.0 months versus 45.1 and 75.5 for patients with focal and diffuse expression, respectively. OS in the group of patients without PML expression, with focal expression, and with diffuse expression was 40, 48, and 77 months, respectively (P=0.002). By a multivariate analysis, PML expression was the strongest prognostic factor for DFS (P=0.003) and the only statically significant prognostic factor for OS (P=0.009). CONCLUSIONS: Our preliminary data suggest PML as a novel prognostic tool for ampullary cancer patients.

Atypical thyroid nodules express both HBME-1 and Galectin-3, two phenotypic markers of papillary thyroid carcinoma.

Ninety-six thyroid lesions were immunohistochemically evaluated for HBME-1 and Galectin-3 expression including nodules with cytological atypia, the latter defined as nuclear features suggestive but not diagnostic of papillary thyroid carcinoma. Thirty nodules with cytological atypia, 49 papillary thyroid carcinomas (PTCs), 4 follicular carcinomas and 13 oxyphilic tumors were examined. Forty-one of the 49 PTCs, 16 atypical thyroid nodules and 3 non-malignant oxyphilic tumors exhibited a combined expression of HBME-1 and Galectin-3. In 6 of the sixteen atypical thyroid nodules the immunoreactivity for both markers was strong and diffuse, simulating the pattern observed in PTC. We conclude that thyroid nodules with cytological atypia and strong/diffuse positivity for both HBME-1 and Galectin-3, two well recognized markers of PTC, represent a starting phenotypic change towards PTC, for which a benign or borderline counterpart has not yet been defined. The expression of HBME-1 and Galectin-3 in some thyroid nodules is related to the presence of cytological atypia suggestive but not diagnostic of PTC. The phenotypic similarity between this subset of thyroid nodules with cytological atypia and PTC is also confirmed by our data according to which Galectin-3 and HBME-1 have been found to be highly sensitive for PTC.

Breast asymmetries: a brief review and our experience.

The authors describe their personal experience with the management of mammary asymmetries. A review of their database from January 1998 to January 2005 identified 177 patients with idiopathic breast asymmetries. All these cases had been classified previously into six groups. Bilateral asymmetric hypertrophy and unilateral hypertrophy were treated with reduction mammaplasty. Unilateral hypertrophy with amastia or hypoplasia of the contralateral side was managed with reduction and augmentation mammaplasty. Unilateral amastia or hypoplasia (Poland's syndrome) was treated with a single monopedicle transverse rectus abdominis muscle (TRAM) flap, and asymmetric bilateral hypoplasia was managed with augmentation mammaplasty. Unilateral mammary ptosis was treated with mastopexy and augmentation mammaplasty. The proposed classification, derived from the authors' experience in this field, gives an idea of how they usually treat these patients. It is useful for a first evaluation, but after that, every treatment must always be individualized on a patient-by-patient basis.

Autologous cartilage graft rhinoplasties.

BACKGROUND: The authors report their experience with autologous graft rhinoplasties. METHODS: Data were collected retrospectively, with selection of only autologous grafts from 2,000 rhinoplasties performed at the Plastic and Reconstructive Department of the University of Rome Tor Vergata. RESULTS: A total of 62 patients from January 1995 to January 2005 were selected. Most of the patients were treated with the "open tip" technique, whereas 9.7% had a classic endonasal approach. Follow-up evaluation was performed with outpatient visits at 2 and 6 weeks, then at 3, 6, and 12 months. Good aesthetic results were obtained for 93.5% of the patients, and 83.7% had complete satisfaction. CONCLUSION: Autologuos cartilage graft rhinoplasty is an affordable technique easy to learn that widens possibilities of interventions for nasal pyramid reconstruction.

Prognostic value of Bax, Bcl-2, p53, and TUNEL staining in patients with radically resected ampullary carcinoma.

BACKGROUND: There is a lack of data in the literature concerning the identification of potential prognostic factors in ampullary adenocarcinoma. AIMS: To examine the prognostic significance of Bax, Bcl-2, and p53 protein expression and the apoptotic index in a large cohort of uniformly treated patients with radically resected ampullary cancer. METHODS: All patients with a pathological diagnosis of ampullary cancer and radical resection were evaluated. Expression analysis for p53, Bax, and Bcl-2 was performed by immunohistochemistry. Apoptotic cells were identified by terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL). RESULTS: Thirty nine tumour specimens from patients with radically resected ampullary adenocarcinoma were studied. A positive significant correlation between Bax and p53 expression was found by rank correlation matrix (p < 0.001). A trend towards a positive correlation was found between the apoptotic index and p53 expression (p = 0.059). By univariate analysis, overall survival was influenced by Bax expression, p53 expression, and TUNEL staining (p = 0.001, p = 0.01, and p = 0.03, respectively). Bcl-2 expression did not influence overall survival in these patients (p = 0.55). By multivariate Cox regression analysis, the only immunohistochemical parameter that influenced overall survival was Bax expression (p = 0.020). CONCLUSIONS: These results provide evidence that apoptosis may be an important prognostic factor in patients with radically resected ampullary cancer. This study is the first to assess the clinical usefulness of Bax expression in radically resected ampullary cancer.

Adrenalitis in the non-obese diabetic mouse.

The non-obese diabetic (NOD) mouse is a model of spontaneous type-1 diabetes used in the field of diabetes research. This study looked at the adrenal glands of NOD and control mice both indirectly in vivo for hormone secretion, and directly in vitro for histological examination. Adrenal glands were taken from NOD mice, of both sexes, at different ages and corticosterone and adrenocorticotropic hormone (ACTH) plasma levels evaluated by radioimmunoassay. There was evidence of lymphocytic infiltration of the adrenal glands, which however, was not accompanied by changes in corticosterone levels. There was a reduction in ACTH levels with age (R2 = 0.98). Mice from other strains (TFW, CBA and Balb/c) showed no lymphocytic infiltration in the adrenal glands and had lower levels of corticosterone than NOD mice of similar ages, but the differences were not significant. In conclusion, since the NOD mouse shows histological signs of adrenalitis, thyroiditis, sialitis and parathyroiditis, this animal can be regarded as a model to investigate mechanisms involved in diffuse lymphocytic infiltration of peripheral endocrine glands (polyendocrine autoimmunity). In addition, if diabetes in the NOD mouse is the result of a polyendocrine disorder rather than a process specific for diabetes, then this finding may have implications for attempts to prevent type-1 diabetes in humans.

Rare presentation of carcinosarcoma arising in bladder diverticulum.

An 87-year-old man presented with hematuria and dysuria. An endoscopic examination revealed a bladder mucosa which was almost entirely occupied by diverticula. On the left lateral wall of the bladder there was a huge diverticulum which contained a 12 cm mass extending beyond the bladder wall in the extraperitoneal tissues. Upon histological examination the mass proved to be a carcinosarcoma which was composed by a squamous carcinoma and a sarcoma resembling a malignant fibrous histiocytoma. The two components, i.e. carcinomatous and sarcomatous, were separated by a sharp collision border and no intermingling was ever noted. The epithelial component showed immunoreactivity for cytokeratin and EMA, while the mesenchymal component was diffusely reactive for vimentin, alpha-1-antitrypsin and lysozime. Both components were reactive for galectin-3, whereas S100, desmin and smooth muscle actin were negative. This is the fourth reported case of carcinosarcoma originating in a bladder diverticulum.