Pentoxifylline and Vitamin E Can Restrict Radiation Necrosis via Vascular Pathways, Experimental Study in an Animal Model.

OBJECTIVE: Radiation necrosis (RN) is a long-term side effect of Gamma Knife stereotactic radiosurgery that may require surgical intervention. Pentoxifylline and vitamin E have previously been shown to be effective in the treatment of RN in the published literature, but there are no data on the prophylactic use of these molecules or, more importantly, whether prophylaxis is required. METHODS: The iatrogenic RN model included 50 Sprague-Dawley rats of both sexes. There were 7 treatment subgroups established. Gamma-Plan 8.32 was used to plan after magnetic resonance scans were performed in a specially designed frame. The injection doses used in the treatment groups were vitamin E (30 mg/kg/day in a single dose) and pentoxifylline (50 mg/kg/day in 2 doses). Control magnetic resonance scans were performed at the end of a 16-week treatment, and the subjects were decapitated for pathological evaluations. RESULTS: The intensity of hypoxia - inducible factor 1α immunoreactivity is statistically significantly lower in the therapeutic vitamin E, prophylactic pentoxifylline and vitamin E, and therapeutic pentoxifylline and vitamin E groups than in the other groups. Similarly, the intensity of vascular endothelial growth factor immunoreactivity was reduced in the therapeutic vitamin E and prophylactic pentoxifylline and vitamin E treatment modality groups. When compared with other groups, the therapeutic pentoxifylline group had significantly fewer vascular endothelial growth factor-immunoreactive cells in the perinecrotic area, with an accompanying decreased contrast enhancement pattern. CONCLUSIONS: Both vitamin E and pentoxifylline are effective for the treatment and/or restriction of RN, either alone or in combination. The use of these molecules as a preventive measure did not outperform the therapeutic treatment.

Past, Present, and Future of Therapies for Pituitary Neuroendocrine Tumors: Need for Omics and Drug Repositioning Guidance.

Innovation roadmaps are important, because they encourage the actors in an innovation ecosystem to creatively imagine multiple possible science future(s), while anticipating the prospects and challenges on the innovation trajectory. In this overarching context, this expert review highlights the present unmet need for therapeutic innovations for pituitary neuroendocrine tumors (PitNETs), also known as pituitary adenomas. Although there are many drugs used in practice to treat PitNETs, many of these drugs can have negative side effects and show highly variable outcomes in terms of overall recovery. Building innovation roadmaps for PitNETs' treatments can allow incorporation of systems biology approaches to bring about insights at multiple levels of cell biology, from genes to proteins to metabolites. Using the systems biology techniques, it will then be possible to offer potential therapeutic strategies for the convergence of preventive approaches and patient-centered disease treatment. Here, we first provide a comprehensive overview of the molecular subtypes of PitNETs and therapeutics for these tumors from the past to the present. We then discuss examples of clinical trials and drug repositioning studies and how multi-omics studies can help in discovery and rational development of new therapeutics for PitNETs. Finally, this expert review offers new public health and personalized medicine approaches on cases that are refractory to conventional treatment or recur despite currently used surgical and/or drug therapy.

Intermediate-Grade Meningeal Melanocytoma in a 19-Month- Old Child with Difficulties in Differential Diagnosis and Management.

Intermediate-grade meningeal melanocytoma (IGM) is a rare tumor that has not been reported in children so far. It is speculated to have more aggressive clinical behavior with undefined best management options. In this study, we present a 19-month-old girl as the first case with IGM in English literature. Preoperative diagnosis was ambiguous, given the unclear patient history and radiological features resembling a growing skull fracture or a congenital parietal bone agenesis subtype. During surgery, a dark gray-black dural area (5 × 7 cm in size) was found and then excised. However, the surgery was complicated due to brain edema and swelling, warranting a second surgery for reconstruction and dural repair. Of the 16 reported adult patients, 14 showed a high recurrence rate without adjuvant radiotherapy; 2 showed no recurrence with adjuvant radiotherapy. No adjuvant radiotherapy was given to our patient since she was 19 months old at the time of diagnosis and showed no recurrence at 48-month follow-up until now. Close monitoring with radiological imaging is of paramount importance for such cases.

Effects of Ozone on Injury after Gamma Knife Radiosurgery.

BACKGROUND: At present, gamma knife radiosurgery plays an important role in neurosurgical procedures. Gamma knife radiosurgery has been used to treat many types of brain tumors and as a functional intervention. However, gamma knife treatment has a devastating effect on the normal brain parenchyma surrounding the target point. It causes increased vascular permeability, vasodilation, and swelling in endothelial cells. Ozone has antioxidant, antiapoptotic, and anti-inflammatory effects in the body. Thus, we evaluated the radioprotective effects of ozone in rats undergoing gamma knife radiation. METHODS: In the present study, 24 Sprague-Dawley male rats weighing 250-300 g in 3 groups of 8 rats each were used. The rats were selected randomly. The control group did not receive any gamma knife radiation. The other 2 groups received 50 Gy of radiation, with 1 group given ozone treatment and the other group not given ozone treatment after gamma knife radiosurgery. At 12 weeks after gamma knife radiation, the rats were sacrificed with high-dose anesthetic agents and the tissues prepared for evaluation. The slides were evaluated for necrosis, vacuolization, glial proliferation, and vascular proliferation using hematoxylin-eosin staining. Vascular endothelial growth factor (VEGF) and extracellular matrix metalloproteinase inducer (also known as CD147) were evaluated using immunohistochemical staining. RESULTS: VEGF expression in glial tissue was significantly less in the group receiving ozone (χ2 = 15.00; df = 4; P = 0.005) compared with the group that had not received ozone and was similar to the expression in the control group. CONCLUSIONS: The lower expression of VEGF in the group receiving ozone might cause less edema in the surrounding tissue owing to less degradation of vascular permeability in the rat brain tissue.

Analyses of Copy Number Variations in Myxopapillary Ependymomas of Cauda Equina.

AIM: To identify the copy number variations that are specific to myxopapillary ependymomas (MPEs) of the cauda equina. MATERIAL AND METHODS: The patient cohort included five patients who underwent resection of histologically confirmed MPEs. Tumor samples collected during surgery and stored in liquid nitrogen as well as corresponding blood samples collected were analyzed. Genomic DNA from the venous blood and tumor samples was obtained using standard techniques and hybridized to a Cytoscan 750K Array in accordance with the manufacturer’s introductions. RESULTS: As a novel finding, amplification on chromosome 14q32.33 was detected in all tumor and blood samples, except one tumor sample. All tumor tissues also showed amplification on chromosomes 5, 7, 9, and 16. CONCLUSION: Although further studies with larger cohorts are required to identify genes involved in MPE tumorigenesis and to validate our results, these findings provide a basis for advanced molecular biological and genetic studies of MPEs.

De novo myeloid sarcoma as a rare cause of small bowel obstruction: CT findings and histopathologic correlation.

Small bowel obstruction caused by myeloid sarcoma in a patient with any hematological abnormality is very rare. Myeloid sarcoma occurs most commonly in patients with acute myelogenous leukemia (AML) and less with other hematological disorders. A 57-year-old female presented with abdominal pain, nausea, vomiting, and constipation. Radiological studies showed concentric bowel thickening in distal ileum that caused nearly total luminal compromise and signs of obstruction in proximal ileal bowel loops. She underwent laparotomic surgery and ileal resection was done. Diagnosis of myeloid sarcoma was made by histopathological examination of surgical specimens. Bone marrow biopsy was done to rule out systemic acute myelogenous leukemia (AML). Results of bone marrow biopsy were within normal limits. Finally, the patient was diagnosed as de novo myeloid sarcoma. Although the histopathological examination makes a definitive diagnosis, imaging allows to locate the lesion, evaluate its complications, and guide for correct biopsy. Accurate diagnosis of myeloid sarcoma has important prognostic value as transformation to AML can happen without chemotherapy or stem cell transplantation.

Significance of H3K27M mutation with specific histomorphological features and associated molecular alterations in pediatric high-grade glial tumors.

PURPOSE: Pediatric high-grade gliomas (pHGGs) constitute almost 15% of all childhood brain tumors. Recurrent mutations such as H3K27M mutation in H3F3A and HIST1H3B genes encoding histone H3 and its variants were identified in approximately 30% of pediatric glioblastomas. This study aimed to ascertain the morphological and molecular characteristics of pHGGs with H3K27M mutation. METHODS: In total, 61 cases of pHGGs (anaplastic astrocytoma, 12; glioblastomas, 49) from four university hospitals were studied. The histomorphological features were examined and immunohistochemistry was performed to evaluate the mutation status of H3K27M, ATRX, IDH1, BRAF V600E, and p53 genes. RESULTS: The study comprised 25 females and 36 males (age range, 1-18 years) with a clinical follow-up of up to 108 months. From the total, 31 patients were positive for H3K27M mutation located in the midline, mostly in the pons and thalamus. H3K27M mutation was commonly associated with ATRX loss (32.3%) and p53 (74.2%) immunoreactivity with a co-expression rate of 25.8%. While IDH1 mutation was not detected in pHGGs with H3K27M mutation, BRAFV600E mutation was rarely observed. Among the various histomorphological features, increased number of mitosis, increased Ki-67 proliferation index, and palisading and geographical necrosis along with small cell patterns were significantly associated with the H3K27M wild-type tumors. Focal infarct-like necrosis and pilomyxoid morphology was significantly associated with these tumors. CONCLUSION: H3K27M mutation occurs exclusively in pHGGs arising from the midline and presents with varied histomorphological features ranging from low-grade pilomyxoid astrocytoma to highly pleomorphic glioblastoma along with ATRX loss and p53 mutations.

The Role of EGFR, Hepatocyte Growth Factor Receptor (c-Met), c-ErbB2 (HER2-neu) and Clinicopathological Parameters in the Pathogenesis and Prognosis of Chordoma.

OBJECTIVE: Chordoma is a rare malignant bone tumor with a poor outcome. Although radiotherapy and gamma knife surgery have been used for treatment, providing a cure for the tumor is not easy, because of the frequent recurrences. Molecular targeted therapy against tyrosine kinases has been effective in the treatment of malignancies such as breast and lung cancers and brain tumors. We aimed to analyse the histopathological features of chordomas and the immunoexpression profiles of the three receptor tyrosine kinases of EGFR, c-Met and c-Erb-B2 in chordomas. We have correlated these results with recurrence and overall survival status of the patients. MATERIAL AND METHOD: We studied 49 chordoma patients in order to evaluate the histopathological features and immunohistochemical stainings by EGFR, c-Met and c-ErbB2 antibodies. Of the 49 patients, follow up data was available for 40 patients. Clinical data of the patients were correlated with histopathological features and survival analysis was performed. RESULTS: The immunostaining rate by EGFR and c-Met was 73.5% and 12.2% respectively. None of the cases showed immunoreactivity by c-ErbB2 (0%). Of the 40 cases, 17 cases showed recurrences. EGFR expression was detected in 14 recurrent (14/17) and 17 non-recurrent cases (17/23). Four of the 17 recurrent cases (4/17) were positive by c-Met, while none of the non-recurrent cases (0/23) were positive by this antibody. Significantly, all cases with positive c-Met expression showed recurrences (p < 0.05). CONCLUSION: Our study indicates that EGFR expression is detected in the majority of chordoma cases. c-Met expression can be used as a prognostic indicator for chordoma.

Solitary Fibrous Tumor of the Orbit: A Case Report and Review of the Literature.

Solitary fibrous tumor (SFT) is a rare, benign, spindle cell tumor that is most commonly found in the visceral pleura. The orbit is one of the most common extrapleural sites of occurrence. Though they can be seen in any age, they typically present in adults with proptosis as the prominent symptom. They show no significant gender predominance. Orbital solitary fibrous tumors routinely exhibit a benign course, but malignant forms with an increased propensity for local recurrence have been reported. Histopathologically, they share similar features with hemangiopericytoma, which is much more common. The diagnosis of SFT depends on the diffuse and intense positivity of CD34 staining by immunohistochemistry (14). Here, we report a case of SFT, which presented with proptosis and double vision on lateral gaze. We describe the clinical, radiographic, histopathological, and immunohistochemical findings. We also provide a discussion on its origin and differential diagnosis in the light of relevant literature.

Metastasis to paranasal sinuses and orbita of breast cancer with a rare metachronous tumor of the uterine cervix.

Breast cancer metastases are rarely seen in paranasal sinuses or orbit with a poor prognosis, and these cases were published as case reports. Moreover, metachronous tumors following breast cancer diagnosis are somewhat common, but uterine cervix is infrequent in them. In the present case, we report a 61-year-old female patient who had a biopsy-proven metastatic breast cancer to paranasal sinuses and orbita. She also had a cervical uterine cancer which is also unusually diagnosed following breast cancer. Palliative radiotherapy to paranasal sinuses (30 Gy) achieved a good response. However, she died due to leptomeningeal progression.

Biologic tumor behavior in pilocytic astrocytomas.

PURPOSE: The aim is to describe the behavior of pilocytic astrocytoma (PAs) and its effects on patient prognosis by using flow cytometric, immunohistochemical and cytogenetic methods. We also aim to find out whether there is any difference between differently localized tumors by the above mentioned analyses. METHODS: We studied DNA index, expression of p53, p16, pRb, MMAC/PTEN1, VEGF, MIB-1 index and chromosomal anomalies which can be detected by array comparative genomic hybridization (CGH) technique. We analyzed the association of the results of these studies with clinical prognosis and tumor localization. We included 53 patients (18 cerebellar, 20 chiasmatic/hypothalamic and 15 hemispheric). Samples were studied from paraffin embedded tumors. RESULTS: We found that PAs are mostly diploid and ploidy pattern does not affect the prognosis. The expression of p53, p16, pRb, MMAC/PTEN1 and VEGF was not significantly different between different localizations and could not predict the prognosis. Frequently seen copy number aberrations (CNAs) are: amplification in 1p36.33, 2p11.2, 9p11.2, 9q12, 16p11.2, 19q13.12-q13.2, Xp22.2-p21.3, Xp11.3-p11.22, Xq11.1-q12, Xq13.1, Xq21.1-q21.31, Xq22.3, Xq26.3 and homozygous deletion in 2p11.2, 8p23.1, 16p12.3. Among them, 2p11.2 amp, 9p11.2 amp and 1p36.21 hom del were correlated with prognosis. Moreover, we found a significant correlation between 16p11.2 amp and tumor localization. CONCLUSIONS: Differently localized PAs have different properties which make them behave with different biological aggressiveness. PAs demonstrate a significant amount of CNAs that can be detected by a high-resolution study. However, tumor suppressor genes p53, p16, pRb, MMAC/PTEN1 and expression patterns do not play a significant role in PAs.

Gamma knife radiosurgery for cranial neurocytomas.

Gamma-knife surgery may be an effective alternative for treatment of central neurocytomas owing to its relative safety compared with conventional radiotherapy. In this paper we present results of gamma-knife treatment (GKS) of residual or recurrent neurocytomas. Twenty-two patients (14 female, 8 male) with recurrent or residual neurocytomas who underwent GKS were included. Diagnosis was based on histological findings. The proliferative potential of the tumors was examined by immunostaining with MIB-1 antibody, which is specific for detection of Ki-67 antigen. Tumor volume was determined by using post-gadolinium magnetic resonance images. After GKS treatment, MR imaging was scheduled at three-month intervals in the first year, at six months intervals in the second year, and yearly thereafter. Histopathological diagnoses were: 18 cases of central neurocytomas, two liponeurocytomas, one cerebral neurocytoma and one cerebellar neurocytoma. The MIB1 labeling index (LI) varied from 0 to 5.7%. Marked reduction in tumor volume was seen in 15 patients. In six patients, the tumor volume remained unchanged, and progression was observed for one patient. No complications because of GKS were noted. Shrinking effect on tumor volume increased with increasing duration of follow-up. On the other hand, high MIB labeling index did not seem to have an effect on tumor response to GKS treatment. Findings of this study suggest that GKS is an effective and safe treatment alternative for residual or recurrent neurocytomas. However, its effectiveness should be confirmed with larger studies.

Effects of parenteral nutritional support with fish-oil emulsion on spinal cord recovery in rats with traumatic spinal cord injury.

AIM: Aim of this study is to assess effects of parenteral nutritional support with fish-oil emulsion on spinal cord recovery in rats with traumatic spinal cord injury. MATERIAL AND METHODS: For 5 days after SCI rats were received saline in group C and Omegaven in group O. Locomotor strengths (BBB scale)of animals were rated at Day 0,7,14,21,28, and 35. At Day 35 spinal cord sampling was evaluated immunohistochemically. RESULTS: BBB scores were 0 in early period after SCI was inflicted in both groups. BBB scores were progressively increased after Day 7 in both groups (p < .005). BBB scores were significantly higher in group O when compared with control group after Day 7 in all times (p < .005). Neuronal injury (p < .002) and edema was much more in control group when compared with in group O (p < .005). Scores for white mater cavitation, demyelinization and vessel in growth were similar in both groups. VEGF expression in control group was higher (p=.019). CONCLUSION: At the early period of SCI fish-oil emulsion treatment in rats, its anti-inflammatory effects leaded to decrease in edema and had positive effect at the prevention of neuronal injury. We believe that nutritional support with fish-oil emulsion in patients with SCI will result in patient's better clinical outcome and increase in quality of the patient's life.

Tumoral calcinosis and epidural lipomatosis of the lumbar spine.

Lumbar spinal tumoral calcinosis and spinal epidural lipomatosis are rare conditions. We present a 70-year-old female patient with serology negative spondyloarthropathy who developed paresis due to tumoral calcinosis in the left facet joint between L5 and S1 levels and spinal epidural lipomatosis at L5 and S1 levels. Surgery was performed to excise the lesions en bloc. Neural decompression was provided. Neurological symptoms improved after surgery. Here, we report the first serology negative spondyloarthropathy case that had concomitant development of tumoral calcinosis and spinal epidural lipomatosis.

Relationship of angiogenic potential with clinical features in cranial meningiomas: a corneal angiogenesis study.

BACKGROUND: Intracranial meningiomas constitute approximately one fourth of all primary intracranial tumors. The invention of cranial angiographic techniques has led to the recognition of the angiogenic potential of meningiomas, which has been the subject of extensive research. OBJECTIVE: To test the relationship between the angiogenetic potential of intracranial meningiomas and clinical/prognostic features such as World Health Organization (WHO) grade, peritumoral edema, tumor border shape, and recurrence using rat corneal angiogenesis assay. METHODS: Fifteen WHO grade I (typical), 10 WHO grade II (atypical), and 5 WHO grade III (malignant) meningioma samples were implanted in the micropockets formed on rat corneas, and the number of developed vessels were counted on days 5, 10, 15, and 20. Normal brain and glioblastoma multiforme tissues served as negative and positive controls, respectively. Patients were evaluated by magnetic resonance imaging preoperatively and every 6 months thereafter. RESULTS: The angiogenic potential of WHO grade II tumors was significantly lower than that of grade III tumors and higher than that of grade I tumors throughout the experiment. Tumors with a smooth border shape and nonrecurrent tumors exhibited significantly lower angiogenic activity compared with the tumors with irregular border shape and recurrent tumors, respectively. No association was found between angiogenic activity and peritumoral edema. However, multivariate analysis identified WHO grade, recurrence, and peritumoral edema as significant predictors of a high angiogenic potential. CONCLUSION: Our findings, based on a dynamic in vivo model to examine angiogenesis, demonstrate that the angiogenic potential of meningiomas is correlated with WHO grade, recurrence, and possibly with tumor border shape and peritumoral edema. Angiogenesis seems to be an important factor in the natural course of meningiomas, suggesting that inhibition of angiogenesis may be an option, particularly in the treatment of meningiomas with an aggressive course.

Expression of angiogenic factors in craniopharyngiomas: implications for tumor recurrence.

BACKGROUND: The primary treatment for craniopharyngiomas is total excision, but recurrence is common. However, current knowledge on the mechanisms of recurrence is limited. OBJECTIVE: We hypothesized that recurrence is linked to the angiogenesis of the tumor. Recurrent and nonrecurrent tumor samples were compared with regard to expression of angiogenesis-related factors and angiogenic capacity in a corneal angiogenesis model. METHODS: Specimens of 4 recurrent and 6 nonrecurrent tumors were selected from 57 patients with adamantinomatous craniopharyngiomas. Sections were immunohistochemically stained with antibodies for vascular endothelial growth factor (VEGF), fibronectin, fibroblast growth factor (FGF)-2, platelet-derived growth factor (PDGF)-A, PDGF-B, platelet-derived growth factor receptor (PDGFR)-alpha, and PDGFR-beta. Expression levels were graded using a 4-point scoring system and were compared. For corneal angiogenesis assay, tissue samples were inoculated in a micropocket created on the rat eye, and microvessels were counted on days 3, 5, 7, and 9 to evaluate angiogenic potential. RESULTS: Expression of PDGFR-alpha and FGF-2 were significantly higher for recurrent tumors (P = .02 and P = .01). However, recurrent and nonrecurrent tumors did not differ in the expressions of other ligands and receptors (PDGF-A, PDGF-B, and PDGFR-beta). Recurrent tumors displayed a higher angiogenic potential starting from the fifth day of corneal angiogenesis assay. CONCLUSION: These findings suggest a relationship between recurrence of craniopharyngiomas and angiogenesis. New treatment modalities with selective PDGFR-alpha blockers may represent a novel and effective therapeutic option for the treatment of craniopharyngiomas.

Effect of smoking on rat basilar artery: correlation with inducible nitric oxide synthase and endothelin converting enzyme-1.

AIM: Smoking is an extremely important risk factor for subarachnoid hemorrhage and seems to increase rupture risk of unruptured aneurysms by accelerating their growth rate. The aim of the study was to investigate the effect of smoking on the luminal diameter with wall thicknesses of rat basilar arteries and to detect alterations of inducible nitric oxide synthase and endothelin-converting enzyme -1 in the endothelial cells. MATERIAL AND METHODS: Rats were divided into two groups. The level of middle pons slices were embedded in paraffin before they were stained with hematoxylin and eosin. Rabbit anti-human inducible nitric oxide synthase and endothelin converting enzyme-1 antibodies were used. RESULTS: Significant decrease of the vessel luminal diameter and increase of the vessel wall thickness were found in chronic smokers in our study. There was a linear and significant (p= 0,023, r =0,704) correlation between thickness of the wall and endothelin converting enzyme-1 immune reaction. Correlation was not found with inducible nitric oxide synthase (p > 0.05). CONCLUSION: This study on the comparison of vessel luminal diameter and vessel wall thickness with inducible nitric oxide synthase and endothelin converting enzyme-1 immune reactions revealed that the main effect of smoking on the vessel wall is associated with endothelin converting enzyme-1.

Immunohistochemical expression of SPARC is correlated with recurrence, survival and malignant potential in meningiomas.

Meningioma is a common neoplasm that constitutes almost 30% of all primary central nervous system tumors and is associated with inconsistent clinical outcomes. The extracellular matrix proteins play a crucial role in meningioma cell biology and are important in tumor cell invasion and in progression to malignancy. SPARC (secreted protein, acidic and rich in cysteine) (osteonectin) is a matricellular glycoprotein that regulates cell function by interacting with different extracellular matrix proteins. The aim of this study was to evaluate the expression of SPARC with proliferation index, p53 reactivity in WHO grade 1 (benign), grade 2 (atypical) and grade 3 (anaplastic) meningiomas and correlate with clinical features of the patients, including location of the tumor, recurrence of the tumor and survival of patients. We studied 111 meningiomas, 69 being benign, 34 being atypical and eight being anaplastic meningiomas of various histological types. Using immunohistochemical analysis, we evaluated the expression of SPARC, Ki-67 (MIB-1) and p53 in meningiomas. Immunohistochemical scores of SPARC were determined as the sum of frequency (0-3) and intensity (0-3) of immunolabeling of the tumor cells. A high immunohistochemical score (4-6) for SPARC was more frequent in atypical and in anaplastic meningiomas than in benign meningiomas (p < 0.01). MIB-1 proliferation index showed significant association between tumor grades in meningiomas (p < 0.01). At the end of a follow-up period of 47.53 +/- 25.04 months, 30 tumors recurred. A high SPARC expression was significantly associated with tumor recurrence (p = 0.02). The immunoreactivity of p53 protein and MIB-1 score were significantly higher in recurrent meningiomas than in non-recurrent meningiomas. The cumulative survival of patients with high SPARC expression was significantly lower than patients with low SPARC expression. The high SPARC expression scores were predominantly identified in meningothelial, fibrous and chordoid meningiomas; low SPARC expression scores were mostly spotted in secretory and psammomatous meningiomas. Evaluating SPARC expression might help assessing recurrence risk and survival estimation in meningiomas.

Human herpes virus 8-unrelated primary effusion lymphoma-like lymphoma: report of a rare case and review of the literature.

A rare case of human herpes virus 8-unrelated primary effusion lymphoma-like lymphoma: a report and review of the literature. APMIS 2009; 117:222-29. Primary effusion lymphoma (PEL) is a very rare type of lymphoma usually confined to the body cavities predominantly in immunosuppressed patients infected with human herpes virus 8 (HHV-8). The new term for HHV-8 independent PEL is HHV8-unrelated PEL-like lymphoma. We describe an 89-year-old human immunodeficiency virus (HIV)-negative male patient with HHV8-unrelated PEL-like lymphoma in the pleura. No hepatosplenomegaly or lymphadenopathy was detected. Chest radiography and computed tomography revealed right pleural effusion, but no evidence of tumor mass or lymph node enlargement. Cytological analysis of the pleural effusion revealed a high-grade lymphoma with round nuclei, prominent nucleoli and abundant cytoplasm with immunophenotypes positive for CD45, CD30, CD38, CD7 and CD71. Because of the advanced age, no chemotherapy was given. Effusion resolved spontaneously. One year after the diagnosis, a new pleural effusion developed at the left side. Following thoracentesis and pleurodesis, the patient remained in complete remission for 40 months. To date, 30 cases of HHV8-unrelated PEL-like lymphoma/HIV negative have been reported in the literature. The outcome of the HHV8-unrelated PEL-like lymphoma patients who were HIV negative seems to be better than HIV- and HHV-8-positive PEL.