In situ mantle cell lymphoma in the nasopharynx.

BACKGROUND: Mantle cell lymphoma (MCL) is a B-cell neoplasm with an aggressive clinical course. Recently, an indolent type of MCL has been described under the term in situ MCL. METHODS AND RESULTS: We report a case of a 70-year-old woman who presented with nasal obstruction. A mass, located in the nasopharynx, was found. Histologic examination revealed lymphoid hyperplasia characterized by CD5 and cyclin D1-positive mantle zone cells, findings consistent with in situ MCL. Three years later, a new biopsy was performed, which showed the same histologic and immunohistochemical (IHC) findings to those observed in the first biopsy. The diagnosis of in situ MCL was confirmed by fluorescence in situ hybridization (FISH) analysis for t(11;14). Since then, the patient has remained free of an overt lymphoma. CONCLUSIONS: In situ MCL may be observed in the nasopharynx, and it would be appropriate to perform cyclin D1 immunostain in cases with marked follicular hyperplasia accompanied by clinical suspicion of lymphoma.

Somatostatin receptor expression in non-medullary thyroid carcinomas.

OBJECTIVE: Peptide receptor radionuclide therapy (PRRT) is dependent upon binding of radiolabelled peptides to their respective receptor expressing cells. The main objective of this study was to characterize the expression of somatostatin receptor (SSTR) subtypes in non-medullary thyroid cancers in order to be able to recommend the use of PRRT as a treatment option in patients with progressive local or metastatic disease. DESIGN: We constructed tissue microarrays from paraffin blocks prepared from 47 cases of non-medullary thyroid carcinomas and related normal thyroid tissue. Immunohistochemical staining was performed with five different polyclonal SSTR antibodies. RESULTS: SSTR subtypes sst2 and sst3 were expressed in all non-medullary thyroid carcinomas, sst1 and sst5 in 75%, and sst4 in 38%. Coexpression of more than three subtypes was detected in 36 of the 47 cases. The expression of SSTR subtypes in normal thyroid tissue was low or absent. CONCLUSIONS: Non-medullary thyroid carcinomas frequently express all SSTR subtypes. This expression provides a basis for further studies with the aim of exploring PRRT as a possible new treatment for iodine-131 refractory metastatic non-medullary thyroid carcinomas.

Synchronous Presence of Nasopharyngeal Carcinoma and Marginal Zone (MALT-Type) B-Cell Lymphoma in the Pharynx.

Synchronous malignancy of squamous cell carcinoma and malignant lymphoma in the head and neck region is extremely rare. Nasopharyngeal carcinoma is a nonlymphomatous, squamous cell carcinoma that occurs in the nasopharyngeal epithelium. Reported herein is a unique case of nasopharyngeal carcinoma occurring simultaneously with MALT-type lymphoma in an 83-year-old woman, who complained of deglutition dysfunction. Endoscopic examination of respective organs revealed a submucosal tumour on the posterior wall of pharynx. Biopsy of the hypopharynx was taken and sent for histological examination, which revealed two different neoplasms. Immunohistochemical and molecular analysis confirmed the diagnosis of nasopharyngeal carcinoma coexisting with a MALT-type lymphoma.

Variable behavior and complications of autologous bone marrow mesenchymal stem cells transplanted in experimental autoimmune encephalomyelitis.

Autologous bone marrow stromal cells (BMSCs) offer significant practical advantages for potential clinical applications in multiple sclerosis (MS). Based on recent experimental data, a number of clinical trials have been designed for the intravenous (IV) and/or intrathecal (ITH) administration of BMSCs in MS patients. Delivery of BMSCs in the cerebrospinal fluid via intracerebroventricular (ICV) transplantation is a useful tool to identify mechanisms underlying the migration and function of these cells. In the current study, BMSCs were ICV administered in severe and mild EAE, as well as naive animals; neural precursor cells (NPCs) served as cellular controls. Our data indicated that ICV-transplanted BMSCs significantly ameliorated mild though not severe EAE. Moreover, BMSCs exerted significant anti-inflammatory effect on spinal cord with concomitant reduced axonopathy only in the mild EAE model. BMSCs migrated into the brain parenchyma and, depending on their cellular density, within brain parenchyma formed cellular masses characterized by focal inflammation, demyelination, axonal loss and increased collagen-fibronectin deposition. These masses were present in 64% of ICV BMASC-transplanted severe EAE animals whereas neither BMSCs transplanted in mild EAE cases nor the NPCs exhibited similar behavior. BMSCs possibly exerted their fibrogenic effect via both paracrine and autocrine manner, at least partly due to up-regulation of connective tissue growth factor (CTGF) under the trigger of TGFb1. Our findings are of substantial relevance for clinical trials in MS, particularly regarding the possibility that ICV transplanted BMSCs entering the inflamed central nervous system may exhibit - under conditions - a local pathology of yet unknown consequences.

Dermatofibrosarcoma protuberans with fibrosarcomatous transformation of the head and neck.

Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous neoplasm associated with a high cure rate. We present a case of aggressive DFSP with fibrosarcomatous areas in the head and neck. A 28-year-old Mediterranean female presented with a 45-day history of rapidly growing cutaneous lesion of the face. Surgical biopsy confirmed the diagnosis of DFSP. Subsequently, the patient underwent wide local surgical resection, followed by reconstruction. Histopathology report revealed fibrosarcomatous transformation and the patient underwent adjuvant radiotherapy. The patient continues to be disease free at the 35-month follow-up.Although DFSP behave as non-aggressive malignancy, surgery with complete removal of the affected area is the intervention of choice. Moreover, adjuvant treatment and follow-up of the patient is essential in order to prevent recurrence.

Ursodeoxycholic acid promotes intestinal adaptation in a cat model of short bowel syndrome.

The aim of this study was to assess the effect of ursodeoxycholic acid (UDCA) on the morphological and functional adaptive response of the jejunal remnant after massive intestinal resection in a cat model of short bowel syndrome (SBS). UDCA was administered to animals at a daily oral dose of 15 mg/kg for 6 weeks following a 85% jejunoileal resection. Resection alone caused extensive hyperplasia of jejunal mucosa, as evidenced by a significant increase in the weight of jejunal mucosa per unit length as well as by significant increases in DNA and protein concentration but no change in the protein/DNA ratio. Morphometric analysis using microscopy revealed no changes in jejunal mucosa thickness, jejunal crypt depth, villus height and villus surface area, although villus thickness was increased. The specific activities of jejunal sucrase and alkaline phosphatase were unaffected. UDCA treatment of resected animals, using doses that caused no toxicity, as evidenced by the absence of serum biochemistry abnormalities and histopathology, did not induce, compared to resection alone, any changes in mucosal cellularity and did not affect villus morphometry. On the other hand, UDCA administration increased crypt depth and, also, induced a profound increase in the specific activity of sucrase. UDCA improved diarrhoea, a core SBS symptom, reflected in a considerably reduced frequency of defaecation and improved form and texture of faeces. It is concluded that UDCA administration may enhance the natural adaptive response of the intestinal remnant following massive jejunoileal resection and may, thus, be beneficial in SBS treatment.

Pilomyxoid astrocytoma of the cervical spinal cord in a child with rapid progression into glioblastoma: case report and literature review.

INTRODUCTION: Pilomyxoid astrocytoma (PMA) is a recently described glial tumor with similarities to pilocytic astrocytomas, yet with distinct histopathological characteristics and a more aggressive behavior. It occurs predominantly in the hypothalamic/chiasmatic region. Only four patients with spinal cord PMA have been reported in the pediatric population. The 2007 WHO Working Group recognized PMA as a new variant and recommended an assignment to WHO grade II. OBJECTIVE: The purpose of this paper was to report a rare location, address the aggressive behavior and rapid progression, and based on the specific patient, to review the literature and discuss current treatment strategies. CASE PRESENTATION: A 12-year-old girl presented with motor and sensory deficits of the left side as well as gait disturbance. Imaging revealed an intramedullary tumor extending from C2 to C7. The patient improved impressively after surgical resection. Histopathological findings were consistent with PMA. Three months later, the patient presented with rapid neurological deterioration. Histopathology after the second operation was consistent with glioblastoma. The outcome was fatal 12 months after initial diagnosis, despite adjuvant therapy. CONCLUSIONS: This is the fifth pediatric spinal cord PMA in literature. Furthermore, it is the only documented patient with rapid recurrence and progression within 3 months into a glioblastoma. The question of a sampling error affecting initial pathology is raised. Based on contemporary literature data, we discuss the further treatment options, as there are no guidelines yet. Efforts towards registries should be encouraged, as the documentation of PMA might lead to more evidence based treatment strategies.

The effect of subconjunctival ranibizumab on primary pterygium: a pilot study.

PURPOSE: A prospective interventional pilot study was performed to estimate the effect of ranibizumab injection on the clinical and histological picture of primary pterygium. METHODS: Five patients with primary pterygia received a single subconjunctival injection of ranibizumab (0.3 mg), whereas 5 nontreated pterygia served as controls. The treated pterygia were surgically removed 3 days, 1 week, 2 weeks, 1 month, and 2 months after the injection, respectively. Digital photographs of the pterygia were taken immediately before injection, 1 week after, and on the day of operation. RESULTS: Ranibizumab was well tolerated by all patients, and no side effects were reported. However, it had no effect on the extent of vascularization of pterygium, regardless of the interval between injection and operation. No regression of pterygium vessels was noted in any of the patients. Immunohistochemical analysis also showed no particular differences in the number of vessels stained positive for vascular endothelial growth factor A, in the intensity of vessel staining among the treated pterygia, and between the treated and the nontreated pterygia. CONCLUSIONS: Subconjunctival ranibizumab at a single dose of 0.3 mg was not associated with any side effects but had no effect on the extent of vascularization of primary pterygium in our study.

Effect of ramipril alone compared to ramipril with eplerenone on diabetic nephropathy in streptozocin-induced diabetic rats.

BACKGROUND/AIMS: We studied the effect of the combined treatment with an angiotensin-converting enzyme (ACE) inhibitor (ramipril) and eplerenone compared with ramipril alone in streptozocin-induced diabetic rats. METHODS: Wistar rats were divided into 4 groups: nondiabetic controls, streptozocin-treated diabetic rats (50 mg/kg), diabetic rats receiving ramipril (1 mg/kg) and diabetic rats treated with the combination of ramipril (1 mg/kg) and eplerenone (100 mg/kg) for 8 weeks. Our model produced early-stage diabetic nephropathy. RESULTS: The diabetic rats developed polyuria, proteinuria, hyperfiltration (assessed by creatinine clearance) and histopathological evidence of renal injury including glomerular hypertrophy and mesangial expansion. Ramipril reduced proteinuria but its combination with eplerenone did not produce any greater benefit. Both treatment approaches prevented glomerular hypertrophy. Addition of eplerenone to ramipril prevented glomerular hyperfiltration. CONCLUSION: Whether eplerenone should be used in addition to an ACE inhibitor or an angiotensin receptor blocker at an early stage of diabetic nephropathy remains questionable.

Clinicopathological correlations in a series of adult patients with non-alcoholic fatty liver disease.

Possible correlations among clinical data, serum aminotransferase levels and histological features were assessed in a series of 37 adult patients with non-alcoholic fatty liver disease (NAFLD), consisting of nine patients with fatty liver (FL) and 28 with non-alcoholic steatohepatitis (NASH). In each liver biopsy, the NAFLD activity score (NAS) and the stage of fibrosis were determined. Additionally, the number of Kupffer cell aggregates (microgranulomas) per centimeter of biopsy length (MG/cm ratio) was assessed on immunohistochemical stains for CD68 antigen. Definite NASH (NAS >or= 5) was strongly correlated with serum aspartate aminotransferase (AST) level (P= 0.003), stage of fibrosis (P= 0.003) and age (P= 0.014). On multivariate analysis, age >46 years and AST level above normal values were found to be independent clinical predictors of established NASH. The MG/cm ratio increased from control liver to FL to NASH (P < 0.001), and was correlated with the NAS (P= 0.003) and with the stage of fibrosis (P= 0.004), but not with the serum aminotransferase levels. In conclusion, persistent AST elevation in patients with suspected NAFLD should be an indication for liver biopsy, in order to determine the severity of necroinflammatory activity and the stage of fibrosis. Microgranuloma counting may represent a useful complementary marker of necroinflammatory activity in patients with NAFLD.

Severe eosinophilic cholangitis with parenchymal destruction of the left hepatic lobe due to hydatid disease.

Hydatid cysts of the liver are known to occasionally rupture into the bile ducts and cause cholangitis. The histological features of this complication have not been adequately described in the literature. Herein is reported a case of severe eosinophilic cholangitis of the left hepatic lobe, occurring in a 24-year-old man with a large (16 cm) hydatid cyst, which obstructed and eroded the left hepatic duct. The patient presented with upper abdominal discomfort and low-grade fever of 3 weeks' duration. Sections of the left lobectomy specimen showed marked inflammatory infiltrates in the portal tracts, predominantly composed of eosinophils, extensively involving bile ducts of all sizes. Occasional small bile ducts were replaced by epithelioid cell granulomas surrounding eosinophilic microabscesses. The inflammatory infiltrates extended into the lobules, resulting in marked hepatocyte loss. This case demonstrates that echinococcosis may cause severe eosinophilic cholangitis with extensive parenchymal destruction, apparently resulting from a hypersensitivity reaction to parasitic antigens.

A rare tumoral combination, synchronous lung adenocarcinoma and mantle cell lymphoma of the pleura.

BACKGROUND: Coexistence of adenocarcinoma and mantle cell lymphoma in the same or different anatomical sites is extremely rare. We present a case of incidental discovery of primary lung adenocarcinoma and mantle cell lymphoma involving the pleura, during an axillary thoracotomy performed for a benign condition. CASE PRESENTATION: A 73-year old male underwent bullectomy and apical pleurectomy for persistent pneumothorax. A bulla of the lung apex was resected en bloc with a scar-like lesion of the lung, which was located in proximity with the bulla origin, by a wide wedge resection. Histologic examination of the stripped-off parietal pleura and of the bullectomy specimen revealed the synchronous occurrence of two distinct neoplasms, a lymphoma infiltrating the pleura and a primary, early lung adenocarcinoma. Immunohistochemical and fluorescence in situ hybridization assays were performed. The morphologic, immunophenotypic and genetic findings supported the diagnosis of primary lung adenocarcinoma (papillary subtype) coexisting with a non-Hodgkin, B-cell lineage, mantle cell lymphoma involving both, visceral and parietal pleura and without mediastinal lymph node involvement. The neoplastic lymphoid cells showed the characteristic immunophenotype of mantle cell lymphoma and the translocation t(11;14). The patient received 6 cycles of chemotherapy, while pulmonary function tests precluded further pulmonary parenchyma resection (lobectomy) for his adenocarcinoma. The patient is alive and without clinical and radiological findings of local recurrence or distant relapse from both tumors 14 months later. CONCLUSION: This is the first reported case of a rare tumoral combination involving simultaneously lung and pleura, emphasizing at the incidental discovery of the two coexisting neoplasms during a procedure performed for a benign condition. Any tissue specimen resected during operations performed for non-tumoral conditions should be routinely sent for pathologic examination.

Angiomatoid fibrous histiocytoma with cystic structures of sweat duct origin.

Angiomatoid fibrous histiocytoma is an unusual soft tissue tumor, mostly arising in the subcutaneous fibro-adipose tissue of children and young adults and measuring a few centimeters in greatest dimension. Reported herein is a unique case of angiomatoid fibrous histiocytoma containing epithelium-lined cystic structures. This large tumor (12 cm) was located in the subcutaneous tissue of the left leg of a 28-year-old woman. The cystic structures were variably sized and were lined by a double cell layer with areas of squamous metaplasia. Their overall histological features suggested a sweat duct origin. Immunohistochemical stains confirmed such origin, demonstrating an inner epithelial and an outer myoepithelial (smooth muscle actin and cytokeratin 17 positive) cell layer. The present case is illustrative of a mechanism of sweat duct dilatation that may occur during the growth of neoplasms involving the dermis and subcutis, resulting in formation of tumors with unusual histological features.

Immunohistochemical distinction between merkel cell carcinoma and small cell carcinoma of the lung.

We assessed the usefulness of several immunohistochemical stains in distinguishing these two neoplasms, including cytokeratin 7, cytokeratin 20 (CK20), neuron-specific enolase, chromogranin, synaptophysin, neurofilaments (NF), thyroid-transcription factor-1 (TTF-1), CD56 antigen, S-100 protein, vimentin, c-erbB-2 oncoprotein, and CD117 antigen. All 13 cases of Merkel cell carcinoma evaluated were positive for CK20, and negative for TTF-1. Twelve of 13 Merkel cell carcinoma cases were positive for NF. Eleven of 13 cases of small cell lung carcinoma were positive for TTF-1. All small cell lung carcinoma cases were negative for NF, and all but one were negative for CK20. In terms of the remaining antigens, there were no differences of significance between the two neoplasms. These findings suggest that a set of three immunohistochemical stains, including CK20, NF, and TTF-1, is useful in affording a distinction between Merkel cell carcinoma and small cell lung carcinoma.

Well-differentiated extraskeletal osteosarcoma: report of 2 cases, 1 with dedifferentiation.

Extraskeletal osteosarcoma (ESOS) is a rare soft tissue sarcoma, typically characterized by high-grade histological features and a grave prognosis. However, 4 cases of well-differentiated ESOS with a better prognosis have been documented in the literature within the last 40 years. We report 2 additional cases, 1 with multicentric presentation and dedifferentiation, and we emphasize the histological features that are useful in distinguishing this lesion from other soft tissue tumors. Well-differentiated ESOS seems to represent a rare but distinct low-grade variant of ESOS. The limited published experience suggests that although the biologic behavior of this tumor is better than that of classical ESOS, there are cases with progression to a higher grade, leading eventually to final demise.

Bone morphogenetic protein expression in newborn rat kidneys after prenatal exposure to radiofrequency radiation.

Effects of nonthermal radiofrequency radiation (RFR) of the global system of mobile communication (GSM) cellular phones have been as yet mostly studied at the molecular level in the context of cellular stress and proliferation, as well as neurotransmitter production and localization. In this study, a simulation model was designed for the exposure of pregnant rats to pulsed GSM-like RFR (9.4 GHz), based on the different resonant frequencies of man and rat. The power density applied was 5 microW/cm2, in order to avoid thermal electromagnetic effects as much as possible. Pregnant rats were exposed to RFR during days 1-3 postcoitum (p.c.) (embryogenesis, pre-implantation) and days 4-7 p.c. (early organogenesis, peri-implantation). Relative expression and localization of bone morphogenetic proteins (BMP) and their receptors (BMPR), members of a molecular family currently considered as major endocrine and autocrine morphogens and known to be involved in renal development, were investigated in newborn kidneys from RFR exposed and sham irradiated (control) rats. Semi-quantitative duplex RT-PCR for BMP-4, -7, BMPR-IA, -IB, and -II showed increased BMP-4 and BMPR-IA, and decreased BMPR-II relative expression in newborn kidneys. These changes were statistically significant for BMP-4, BMPR-IA, and -II after exposure on days 1-3 p.c. (P <.001 each), and for BMP-4 and BMPR-IA after exposure on days 4-7 p.c. (P <.001 and P =.005, respectively). Immunohistochemistry and in situ hybridization (ISH) showed aberrant expression and localization of these molecules at the histological level. Our findings suggest that GSM-like RFR interferes with gene expression during early gestation and results in aberrations of BMP expression in the newborn. These molecular changes do not appear to affect renal organogenesis and may reflect a delay in the development of this organ. The differences of relative BMP expression after different time periods of exposure indicate the importance of timing for GSM-like RFR effects on embryonic development.