High-dose chemotherapy and autologous stem cell transplantation in primary lymphomatoid granulomatosis of the central nervous system.

Primary lymphomatoid granulomatosis of the CNS (CNS-LG) is a rare lymphoid neoplasia associated Epstein-Barr Virus (EBV) and often accompanied by immunodeficiencies. No treatment standards have been defined yet. However, due to often devastating neurologic sequelae and based on similarities to diffuse large B-cell lymphoma, curative treatment requires intensive therapy protocols resembling protocols applied in CNS lymphoma. Here, the clinical courses and treatments of four primary CNS-LG patients in analogy to aggressive CNS-lymphomas including methotrexate, thiotepa, cytarabine, carmustine, and rituximab are presented. This is the first report on high-dose chemotherapy with CNS-directed drugs and autologous blood stem cell transplantation in primary CNS-LG.

Hematopoietic stem cell transplantation in patients with lymphomatoid granulomatosis: a European group for blood and marrow transplantation report.

Lymphomatoid granulomatosis (LG) is a very rare, Epstein-Barr virus-associated lymphoproliferative disorder of B cells. Prognosis is poor, particularly after relapse and no curative treatment exists. We report the results of high-dose therapy and autologous stem cell transplantation (ASCT) or reduced-intensity conditioning and allogeneic stem cell transplantation (alloSCT) in patients with multiply relapsed LG. A European Group for Blood and Marrow Transplantation survey identified 10 patients who had received 9 ASCT and 4 alloSCT. All patients had active disease at the time of transplantation. With a median follow-up of 5.1 (range, 1.4 to 6.3) years, 6 patients are alive and disease-free. Two ASCT patients died of septicemia early after transplantation, and 1 committed suicide after being in continuous complete remission 19 months after ASCT. Another patient allografted 4 years after ASCT remained disease-free but died of severe graft-versus-host disease 3 months after alloSCT. High-dose therapy followed by ASCT and alloSCT are effective therapeutic options and should be considered in all patients with refractory and multiply relapsed LG.

Pulmonary lymphomatoid granulomatosis mimicking lung cancer.

Lymphomatoid granulomatosis (LYG) of the lung is an extremely rare, Epstein-Barr virus-related lymphoproliferative disease. We report a case of pulmonary LYG that presented as a large necrotic mass.

[Pulmonary lymphomatoid granulomatosis: an immunohistochemical and gene rearrangement study].

OBJECTIVE: To study the immunophenotype and gene rearrangement pattern of pulmonary lymphomatoid granulomatosis. METHODS: Nine cases of pulmonary lymphomatoid granulomatosis, included 5 cases of open lung biopsy, 3 cases of lobectomy specimen and 1 case of autopsy, were retrospectively analyzed by immunohistochemistry, in-situ hybridization for Epstein-Barr virus-encoded RNA, immunoglobulin and T-cell receptor gene rearrangement studies. RESULTS: The age of patients ranged from 3 to 59 years. The male-to-female ratio was 3: 6. Histologically, all cases showed lymphocytic infiltration surrounding the blood vessels and in the perivascular areas. Most of these lymphoid cells expressed T-cell marker CD3. There were also variable numbers of CD20-positive B cells. The staining for CD56 was negative. According to the WHO classification, there were 4 cases of grade I , 1 case of grade II and 4 cases of grade III lesions. Six cases had gene rearrangement studies performed and 3 of them demonstrated clonal immunoglobulin gene rearrangement (including 1 of the grade II and 2 of the grade III lesions). No T-cell receptor gene rearrangement was detected. CONCLUSIONS: Pulmonary lymphomatoid granulomatosis may represent a heterogeneous group of lymphoproliferative disorders. Some of the cases show B-cell immunophenotype and clonal immunoglobulin gene rearrangement, especially the grade II and grade lesions. They are likely of lymphomatous nature.

Spontaneous regression and regrowth of central nervous system lymphomatoid granulomatosis: case report.

A 74-year-old woman presented with central nervous system (CNS) lymphomatoid granulomatosis (LYG) that spontaneously regressed and then regrew shortly thereafter. Initial magnetic resonance imaging studies showed a well demarcated, round, enhanced lesion with perifocal edema in the left temporal lobe. The enhanced lesion and perifocal edema had drastically regressed without treatment at follow-up examination. Two months later, the lesion reappeared and was larger, so was completely removed via left fronto-temporal craniotomy. The histological diagnosis was CNS LYG. CNS LYG should be considered in the differential diagnosis of spontaneously regressing brain tumors.

[Primary central nervous system lymphomatoid granulomatosis: a case report].

Lymphomatoid granulomatosis (LYG) is a rare Epstein-Barr virus-associated multisystem lymphoproliferative and granulomatous disease histologically characterized by angiocentric and angiodestructive cellular infiltrate. LYG usually involves the lungs, skin, kidneys and brain, but isolated central nervous system LYG has been reported rarely. We describe a 57-year-old man with histologically proved LYG confined to the brain. The patient complained of visual disturbance, and was admitted to our hospital. Gadolinium-enhanced T1-weighted MRI showed irregular, partly cystic and lobulated enhancement in the left occipital lobe, suggesting the presence of possible neoplastic lesions such as glioma, malignant lymphoma or metastatic brain tumor. We performed surgical resection of the lesion. Histological and immunohistochemical examinations of the tumor showed angiocentric polymorphic infiltration and granulomatous reaction, consisting of CD3-positive small lymphocytes and CD20-positive large atypical cells. Subsequently, in situ hybridization study for EBER (Epstein-Barr virus encoded small RNA) was performed and proved that the large atypical cells were positive for EBER. These findings were compatible with LYG. We emphasize that the possibility of LYG should be considered in the differential diagnosis of any ring-like enhancing mass lesions on MR images, though less specific for LYG. Histopathological examination is indispensable for the final diagnosis and the choice of an optimal treatment strategy.

Tumoral presentation of primary central nervous system lymphomatoid granulomatosis.

PURPOSE: Lymphomatoid granulomatosis (LYG) is an angiocentric Epstein-Barr virus (EBV) related B-cell proliferation associated with a reactive T-cell component with an uncertain malignant potential. LYG present at diagnosis as a mass lesion in the central nervous system (CNS) is rare, and only a few cases have been reported. In this article we present four cases of tumoral CNS-LYG and propose some guidelines for its management. METHODS: Clinical, pathological, imaging and laboratory information of four immunocompetent patients, all of them treated surgically, with a final diagnosis of LYG and presenting with an isolated intracranial tumoral mass is reviewed. RESULTS: Two parenchymal lesions were located in the cerebellum and temporal lobe, and the other two involved the cavernous sinus. At surgery they were avascular, hard, lard-like, necrotic and plastic well-defined lesions, with invasion of the leptomeninges and thrombosis of the small leptomeningeal arteries and veins. Intraoperative pathology excluded any tumor. Pathological studies showed a polymorphic and polyclonal infiltration around, in the wall and into the lumen of medium-sized cortical and leptomeningeal vessels causing their obstruction and tissular necrosis. EBV-infected cells were present. CONCLUSIONS: Making a preoperative diagnosis of CNS-LYG appearing initially as a tumoral mass is difficult because of the lack of pathognomonic clinical symptoms or imaging signs. Surgical management with radical resection of the mass is almost always followed by the long-term local control of the lesion, although the disease may have a disseminated, systemic or malignant evolution.

Cervical extramedullary lymphomatoid granulomatosis.

Lymphomatoid granulomatosis (LYG) is a rare multisystem disease involving most frequently the lung, kidney and skin. LYG is characterized by an infiltration of atypical lymphocytoid and plasmocytoid cells, with granulomatous inflammation in an angiocentric and angiodestructive pattern. There have been only a few reports of spinal involvement of LYG. To our knowledge, we report the first patient with cervical extramedullary LYG undergoing surgical removal of a lesion causing spinal cord compression, and review the pertinent literature. The patient underwent C5-partial T1 laminectomy with partial removal of the lesion and decompression of the spinal cord. A diagnosis of a grade III LYG was made and chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) was administered. The patient was in good neurological condition at the 6-month follow-up but died 5 months later because of systemic progression of the disease. Although prognosis of LYG remains poor, surgery can be considered to improve pain relief and neurological morbidity of spinal LYG.

Primary cerebral lymphomatoid granulomatosis: report of four cases and literature review.

BACKGROUND: Lymphomatoid granulomatosis (LYG) is an angiocentric and angiodestructive lymphoreticular proliferation, which usually involves the lungs, but may also involve the central nervous system (CNS). Unique involvement of the CNS has been reported rarely. We report our experience with LYG confined to the brain and review the pertinent literature. PATIENTS AND METHODS: From January 1995 to September 2007, we identified patients with isolated brain LYG through a search of the histopathology database of the Catholic University of Rome; medical and radiological data were analyzed. Immunophenotype, in situ hybridization analysis of EBV-encoded small RNAs (EBER ISH) and immunoglobulin rearrangement studies were performed on the pathological specimens. RESULTS: Four patients with brain-LYG (male/female 1:1, mean age 44 years) underwent surgery in the study period. Subsequent therapy was tailored according to LYG grading. At the latest follow-up (range from 18 to 221 months), patient conditions had improved in all cases. EBER ISH was negative in all cases. Study of the IgH chain gene documented a monoclonal pattern in two cases. CONCLUSIONS: CNS-LYG is a rare disease that should be considered in the differential diagnosis of both diffuse and space-occupying cerebral lesions. Primary cerebral LYG seems not to be associated with EBV and appears to have a better prognosis than systemic LYG with CNS localization, which is frequently EBV positive.

A case of central nervous system lymphomatoid granulomatosis; characteristics of PET imaging and pathological findings.

Lymphomatoid granulomatosis (LYG) in the central nervous system (CNS) is an uncommon lymphoproliferative disorder with low grade malignant potential. Here we report a case of CNS-LYG, in particular, its characteristics of radioisotope imaging and pathological findings. A 65-year-old man complained of visual disturbance and homonymous hemianopsia was designated. CT and MRI revealed an edematous, enhanced irregular and nodular lesion in the right occipital and parietal lobes. Although 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) scan showed low uptake in the lesion, Methionine (MET)-PET scan indicated high uptake. Proton magnetic resonance spectroscopy ((1)H-MRS) at 3T revealed a decrease of the peak of the N-acetylaspartate (NAA), suggesting a possible neoplastic lesion. The patient was diagnosed with CNS-LYG based on the surgically removed material showing perivascular infiltration of CD3-positive small T-lymphocytes with granulomatous lesions. The post-operative steroid therapy was effective and the recurrence or exacerbation has not been observed by radiological imaging until now.

[Laparoscopic splenectomy through a lateral access]. / Laparoskopicheskaia splenéktomiia iz lateral'nogo dostupa.

The investigation included 35 patients with diseases of blood and spleen pathology (30) and wounds and traumas of the abdomen with injuries of that organ (5), treated by laparoscopic splenectomy through a lateral access. The technique and stages of the operation and advantages of the lateral access are described. The laparoscopic splenectomy was shown to be possible in 90% of cases if patients were selected with special reference to the main disease, size and degree of pathological alterations in the spleen. An adequate approach to selections of patients with injuries of the organ allowed to make operations in more than a third of the patients and casualties. When using the lateral access laparoscopic splenectomy is thought to be more convenient, gives better visualization of the anatomical structures and reduces risk of injury of adjacent organs, thus resulting in less frequency of complications and conversions.

[Granulomatous thymitis with stromal amyloidosis]. / Ganulomatoznyi timit s amiloidozom stromy.

In a surgically removed thymus of an 18 year old man granulomatous thymitis with lymphoid follicles, amyloidosis, pseudocysts were observed. Rare occurrence of this pathology, difficulty of the diagnosis, absence of the treatment concept make surgery a method of choice.

[Coexistence of choanal polyp and lymph node tuberculosis]. / Wspólistnienie polipa choanalnego i gruzlicy wezlów chlonnych.

The authors present a case of coexistence of choanal polyp and lymph node tuberculosis in patient referred to ENT Clinic of K. Marcinkowski University of Medical Sciences in Poznan with suspicion of nasopharyngeal malignant tumor and lymph node metastases. Performed surgery and histopathological evaluation of obtained tissues revealed lymph node tuberculosis and polyp.

[A case report of lymphomatoid granulomatosis (LYG) with spontaneous attenuation].

70 years old woman was admitted to our hospital for the evaluation of multiple nodular shadows on chest X-ray. She had no clinical symptoms despite of mild increase of LDH and decrease of PaO2 on laboratory examination. Video associated thoracic surgery was performed to obtain lung tissue for the pathological diagnosis. Pathological findings suggested a diagnosis of lymphomatoid granulomatosis (LYG) for her lung nodules, which was confirmed by rearrangement of IgJH with nested PCR of lung tissue. Nodular shadows in her lung had a trend to regress in accordance with decreases of makers for lymphoma such as sIL-2 R, thymidine kinase, and beta 2-microglobulin without any medication. This is a rare case report of LYG with spontaneous attenuation in the clinical course.

Exclusive CNS involvement by lymphomatoid granulomatosis in a 12-year-old boy: a case report.

BACKGROUND: Lymphomatoid granulomatosis [LYG] is an angiocentric, angiodestructive disease at the higher grade end of the spectrum of angiocentric immunoproliferative lesions. It primarily involves the lungs, but it may also involve several extrapulmonary sites including the central nervous system (CNS), skin, and kidneys. CASE DESCRIPTION: Clinical presentation, radiology and treatment of LYG in a 12-year-old male child with multiple intracranial extraaxial lesions is described. A 12-year-old boy presented with sudden onset of left focal motor seizures with associated history of headache and vomiting. Computerized tomographic scan of the brain suggested high-density, bilateral, parietal extraaxial lesions. On magnetic resonance imaging, the lesions were iso- to hyperintense on T1-weighted images and hyperintense on T2-weighted images. The lesions were excised in two stages and histopathological examination confirmed the diagnosis. CONCLUSION: LYG seldom involves the CNS exclusively. The present case demonstrates exclusive CNS involvement by LYG in a young boy.

Lymphomatoid granulomatosis of the lung: a clinico-pathological study.

Lymphomatoid granulomatosis is the only form of pulmonary angiitis histologically characterized by a necrotizing angiocentric and angiodestructive lymphoid infiltrate, with an admixed T-cell reaction. We evaluated three patients with a single lung nodule not diagnosed by routine radiological and endoscopic assays. Our investigations showed a prevalence of T-cells in areas of diffuse infiltration, which were actively replacing reactive follicular areas of B-cells, similarly to T-cell lymphomas. Further pathologic assays suggested the histologic diagnosis of grade I lymphomatoid granulomatosis for all three evaluated specimens. After two years, patients treated with a combination of surgical resection and chemotherapy were disease free, supporting the efficacy of aggressive therapy in the management of this often mistreated group of lymphoid proliferations.

Isolated cerebellar lymphomatoid granulomatosis progressing to malignant lymphoma. Case report.

A 60-year-old man presented with progressive and unique neurological symptoms. Investigations identified an isolated cerebellar lesion. This lesion fulfilled the histological criteria for lymphomatoid granulomatosis, and in situ hybridization and deoxyribonucleic acid (DNA) dot blot techniques revealed significant amounts of Epstein-Barr virus DNA within the tumor cells. The patient underwent cranial radiation therapy, and 16 months after the initial presentation the lesion evolved into a malignant lymphoma. He subsequently died secondary to subdural empyema, bacterial meningitis, and bronchopneumonia. The unique clinical and etiological aspects of this case are addressed.