Lymphomatoid granulomatosis: A case series from South India.

CONTEXT: Lymphomatoid granulomatosis (LYG) is a rare B-lymphoproliferative disorder characterised by an angiocentric and angiodestructive pattern along with Epstein - Barr virus (EBV) association. It is one of the diagnostic challenges in lymphoma pathology. Deregulation of EBV immune surveillance is one of the narrated hypotheses in the literature. Extrapulmonary manifestations are rare with LYG. Morphological grading is done based on the number of EBV-positive B cells, which is useful to strategize treatment protocol. AIMS: We report here a series of nine cases of LYG to discuss the clinical, histological, and immunohistochemistry findings. SETTINGS AND DESIGN: This is the first case series from India in published literature. SUBJECTS AND METHODS: We reviewed cases of LYG diagnosed at our center for the past 11 years (2006-2016). A total of nine cases were included in this study. Histomorphology was studied in conjunction with immunohistochemistry and clinical details. Cases without classical morphology and negative for EBV immunostain were excluded from the study. RESULTS: There were nine patients in our study (7 males and 2 female; M:F ratio 3.5:1). The age of these patients ranged from 4 years to 57 years (mean age: 30 years). The most common site involved was the lung (4, 44%), followed by the skin (2, 22%), central nervous system (2, 22%) and lymph node (1, 11%). One patient had primary immunodeficiency. Another patient had undergone renal transplant 11 years before the development of the lesion. Angiocentricity and angioinvasion were appreciated in all nine cases (9/9) with necrosis in four cases (44%) and ill-defined histiocytic aggregates in three cases (33%). The histological features were as follows: Grade 1(4 cases, 44%), Grade 2(2 cases, 22%), and Grade 3(3 cases, 33%). CONCLUSION: LYG is a rare EBV driven angiodestructive disease with predominantly lung involvement as well as isolated extrapulmonary sites as seen in our study. It is often progressive and ultimately fatal in the absence of appropriate treatment. Grading of the lesion helps to initiate the appropriate treatment of choice.

Lymphomatoid Granulomatosis: A Single Institution Experience and Review of the Literature.

BACKGROUND: Lymphomatoid granulomatosis (LYG) is a rare B-cell lymphoproliferative disorder with frequent extranodal presentation and involvement of the respiratory system. The purpose of this study is to describe the clinical characteristics, pathologic findings, and treatment outcomes of LYG in a single tertiary institution. METHODS: This is a retrospective review of series of cases of LYG diagnosed at Moffitt Cancer Center (MCC) between 2000 and 2011. We describe clinical presentation, histopathologic findings, and treatment outcomes. RESULTS: We identified 11 cases of biopsy-proven LYG at our institution. All patients presented with lung involvement by LYG. Nine patients were treated with rituximab-based chemotherapy. The overall response rate was 63.6% (complete response rate, 36.44%). Extra-pulmonary involvement was common (central nervous system, kidney, adrenal glands, testicles, and liver). The median overall survival and progression-free survival were 23 and 12.2 months, respectively. CONCLUSIONS: LYG is a rare B-cell lymphoproliferative disorder with involvement if the respiratory system. The presentation is heterogeneous, and response to therapy is variable. Although it is considered a poor prognosis disease, long-term survivors in remission have been described.

Fatal B-cell lymphoma following chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids.

IMPORTANCE: Recent reports on chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) suggest that patients who have a relapse respond very well and that disease progression can be avoided if timely corticosteroid therapy is started. We report on a well-documented patient who presented with clinical, radiological, and pathological characteristics of CLIPPERS and who had an unfavorable outcome. OBSERVATIONS: We present the clinical, imaging, laboratory, brain biopsy, and autopsy findings of a 57-year-old male patient with CLIPPERS who repeatedly responded well to high-dose corticosteroids. During follow-up, however, treatment failed, and he had a biopsy-confirmed diagnosis of lymphomatoid granulomatosis that evolved into fatal B-cell lymphoma of the central nervous system. CONCLUSIONS AND RELEVANCE: The clinical and imaging features of CLIPPERS include an abundance of differential diagnoses, and the follow-up periods of the described cases classified as CLIPPERS have been limited. Therefore, the question remains whether CLIPPERS is an actual new disease entity or represents a syndrome that includes different overlapping diseases and their prestages. Our case report shows that a typical presentation of CLIPPERS does not uniformly imply a favorable outcome, even when timely treatment regimens have been given.

Lymphomatoid granulomatosis: insights gained over 4 decades.

Lymphomatoid granulomatosis is a rare lymphoproliferative disease involving predominantly the lung, and there is uncertainty about its relationship to lymphoma. It affects mainly middle-aged adults, although there is a wide age range, and men are affected almost twice as often as women. Multiple nodular, usually bilateral, infiltrates are seen radiographically, and extrapulmonary involvement, especially of skin and nervous system, occurs in more than one third of the patients. Mortality rates are high, and treatment modes are not well established. Morphologically, there is a nodular polymorphous mononuclear cell infiltrate with prominent vascular infiltration and often necrosis. Varying numbers of large, often atypical, CD20-positive B-lymphocytes are present within a background containing numerous CD3-positive small T lymphocytes and scattered admixed plasma cells and histiocytes. Evidence of Epstein-Barr virus infection can be shown in most cases by in-situ hybridization for Epstein-Barr virus RNA. The infiltrate is graded as 1 to 3 based on the proportion of large B cells. Morphologically, there is overlap in grades 2 and 3 with variants of large B-cell lymphoma, and many such cases show evidence of monoclonality by polymerase chain reaction. It is suggested that lymphoma (T-cell rich large B-cell or diffuse large B-cell) be diagnosed in addition to lymphomatoid granulomatosis in grades 2 and 3 to appropriately communicate the nature of the disease to clinicians.

Lymphomatoid granulomatosis with long survival.

We present a case of lymphomatoid granulomatosis presenting in a 35-year-old Saudi lady with long survival. She responded to treatment with intermittent cyclophosphamide infusion in addition to corticosteroids. This is the first case of lymphomatoid granulomatosis to be reported in the Arab world. The prolonged survival and response to intermittent cyclophosphamide infusion is discussed.

Treatment of localized non-Hodgkin's lymphomas of the head and neck: focusing on cases of non-lethal midline granuloma.

This report clarifies the prognostic factors for survival in localized non-Hodgkin's lymphoma (NHL) of the head and neck and defines optimal regimens for this disease. One hundred-seven untreated patients with Stage I or II NHL of the head and neck were treated with involved field radiation therapy for orbital, nasal, or paranasal lymphoma and extended field radiation for Waldeyer's ring or neck lymphoma. Radiation doses were 39-48 Gy. In the latter half of the study, adjuvant chemotherapy was administered. Of 107 patients, 95 achieved complete response (CR). Of the 12 patients that did not achieve CR, 9 had nasal T-cell lymphoma (NTL) of the lethal midline granuloma type (LMG-NTL). Only one patient who obtained CR relapsed in a previously irradiated area. Age, sex, stage, bulky mass, number of involved sites, LMG-NTL, histologic subtypes, radiation dose, and adriamycin dose were analyzed for prognostic significance for disease-specific survival in NHL by multivariate analysis. LMG-NTL was the most significant prognostic factor (P < 0.001). Patients with higher age also experienced a higher relative risk than patients of > or =60 years of age (P = 0.0063). Dose of adriamycin reached the borderline significance (P = 0.0600). Radiotherapy is excellent for obtaining local control of head and neck NHL. Randomized trials are required to determine the appropriate radiation field and dose in patients previously treated with chemotherapy. LMG-NTL and age were the significant prognostic factors for disease-specific survival.

Malignant lymphomatoid granulomatosis infiltrating myocardium and producing sudden death.

The case of a 70 year old man suddenly deceased by myocardial lesions produced by a malignant pulmonary lymphomatoid granulomatosis is reported. The light microscopic pattern of the pulmonary, lymph node and myocardial lesions showed a polymorphous immunoblastic lymphoma.

Clinical implications of the histopathologic diagnosis of pulmonary lymphomatoid granulomatosis.

We reviewed the epidemiologic, laboratory, roentgenographic, pulmonary function, and survival data from 28 patients who had a histologic diagnosis of lymphomatoid granulomatosis (LG) with involvement of the lungs. The mean age at the time of diagnosis was 51 years, and the male-to-female ratio was 3:2. Ten patients had other underlying diseases before LG was diagnosed. The most prominent symptoms were cough, dyspnea, fever, and rash, which were usually present for several months before diagnosis of LG. Multiple nodules were detected on a chest roentgenogram in 68% of the patients. Immunoglobulin concentrations were abnormal in 8 of 12 patients studied. Although bronchoscopy established the diagnosis in approximately a third of the patients who underwent this procedure, open-lung biopsy was uniformly diagnostic. The median survival was 72 months, with follow-up through 12 years. In 11 patients, the original diagnosis of LG was eventually changed to lymphoma. In five of these patients, the change in diagnosis was based on immunohistologic data obtained shortly after LG was discovered. Lymphoma diagnosed in this way was associated with a better prognosis than lymphoma diagnosed on the basis of conventional histopathologic findings. In three patients, solid tumors eventually developed. The diversity of clinical outcomes and frequent revisions of the diagnosis led us to consider the possibility that LG may also represent a histopathologic finding that occurs transiently in several disease processes.

Lymphomatoid granulomatosis of the larynx in a renal transplant recipient.

This is a case of lymphomatoid granulomatosis in a renal transplant patient, which presented as an ulcerating pharyngeal lesion and caused death by exsanguination from carotid artery erosion. The diagnosis was established at limited necropsy on the basis of a characteristic vaso-infiltrative and atypical lymphoreticular infiltration as defined by Liebow, et al, in 1972. As far as can be ascertained, this is the second reported case of lymphomatoid granulomatosis in an immunosuppressed patient and also is a presumed localized extrapulmonary form of this disorder which has recently been reported. The striking histologic similarities to midline malignant reticulosis are discussed.