Extranodal noncutaneous lymphoid hyperplasias represent a continuous spectrum of B-cell neoplasia: demonstration by molecular genetic analysis

We investigated 16 lymphoid proliferations occurring in the ocular adnexa, salivary glands, breast, and thyroid gland and satisfying the histopathologic and immunophenotypic criteria of benign lymphoid hyperplasia for the presence of clonal rearrangements of the antigen receptor, c-myc, bcl-1, and bcl-2 genes and Epstein-Barr virus (EBV) DNA sequences. Each of these 16 extranodal, noncutaneous lymphoid neoplasms exhibited clonal immunoglobulin heavy and/or light chain and lacked T-cell receptor (TCR) beta-chain gene rearrangements. The patterns of immunoglobulin gene rearrangements included solitary and multiple barely perceptible to faint bands, solitary clear and definite bands, and solitary high-intensity bands superimposed on a background of multiple less-intense bands. Three ocular adnexal lymphoid neoplasms exhibited bcl-1 or bcl-2 gene rearrangements. None of the 16 lymphoid neoplasms contained EBV DNA sequences. Two patients developed a histopathologically confirmed malignant lymphoma in an extranodal site. None of the remaining 14 patients developed additional lymphoid neoplasms during a mean follow-up period of 30 months, despite conservative therapy. These results demonstrate that extranodal, noncutaneous lymphoid neoplasms meeting the histopathologic and immunophenotypic criteria for benign lymphoid hyperplasia frequently contain occult monoclonal and oligoclonal B-cell populations representing a continuous and progressive spectrum of B-cell neoplasia up to and including malignant lymphoma.     

Tumors of the thymus.

Thymic neoplasms are a common cause of an anterior mediastinal mass and may be benign or malignant. Thymic cysts are congenital or acquired and may be associated with a thymic malignancy. True thymic hyperplasia and thymic lymphoid hyperplasia may enlarge the thymus and simulate a neoplasm. Thymoma and thymic carcinoma are epithelial malignancies with distinct clinicopathologic features. Thymic carcinoid is a rare aggressive neuroendocrine malignancy associated with multiple endocrine neoplasia 1. Thymolipoma is a benign neoplasm. Hodgkin and non-Hodgkin lymphoma may primarily or secondarily involve the thymus. Primary mediastinal germ cell tumors may arise primarily within the thymus and include mature teratoma, seminoma, and non-seminomatous malignant germ cell tumors.     

Intestinal nodular lymphoid hyperplasia and extraintestinal lymphoma--a rare association

Nodular lymphoid hyperplasia of the gastrointestinal tract is characterized by the presence of innumerable small discrete nodules involving a variable segment of the gastrointestinal tract. The association between nodular lymphoid hyperplasia and other benign and malignant diseases has been clearly described, with an increased risk of gastrointestinal tumours, namely gastrointestinal lymphoma. However, the association with extraintestinal lymphoma seems extremely rare. The authors present a clinical case of a patient with nodular lymphoid hyperplasia of the small and large intestine that subsequently developed an extraintestinal lymphoma (diffuse large B-cell lymphoma).     

Rectal tonsil:A case report and literature review

The rectal tonsil,a reactive proliferation of lymphoidtissue located in the rectum,is rare.Histologically,benign lymphoid hyperplasia of the rectum is usuallycharacterized by large lymphoid follicles with activegerminal centers and a narrow surrounding mantlezone and marginal zone.This lesion is benign,but must be differentiated from the polypoid type of mucosaassociated lymphoid tissue lymphomas.In the current paper,we present a case of rectal tonsil in a 59-yearold woman.We describe the endoscopic ultrasound imaging findings with literature review.     

Ileocecal intussusception in an adult: A case report.

Intussusception is relatively rare in adults and differs from the childhood form in its etiology, presentation and treatment. Unlike childhood intussusception, adult intussusception is usually due to underlying pathologic lead points, most probably neoplasms. The main clinical presentation of intussusception in the adult is chronic abdominal pain, and acute adult intussusception is uncommon. Here, we describe an uncommon case of acute ileocecal intussusception due to ileal lymphoid hyperplasia in a 46-year-old woman. Lymphoid hyperplasia of the intestines is a benign reactive process. Intestinal lymphoid hyperplasia has been reported in association with infections and as an allergic response to various foods. In adults, it has been reported to occur in association with immune deficiencies. There were no obvious causes for this patient's ileal lymphoid hyperplasia. We conclude that physicians need to consider intussusception, due to intestinal lymphoid hyperplasia, as a possible cause of acute abdominal pain in adults, even in the absence of any specific medical history.     

Jejunal Malignant Lymphoma in a Patient with Adult-Onset Hypo-γ-Globulinemia and Nodular Lymphoid Hyperplasia of the Small Bowel

A malignant lymphoma of the small bowel developed in a 55-yr-old woman who had intestinal malabsorption for 20 yr, late-onset hypo-gamma-globulinemia, and nodular lymphoid hyperplasia. The tumor arose in the first jejunal loop and appeared to be of B-immunoblastic type (diffuse large noncleaved cells). This case indicates that nodular lymphoid hyperplasia in the context of immunodeficiency may be a condition leading to lymphoid malignancy.     

Nodular lymphoid hyperplasia in endoscopic and FDG-PET/CT (18F-fluoro-2-deoxyglucose positron emission tomography/computerized tomography) imaging

Gastrointestinal nodular lymphoid hyperplasia is a rare lymphoproliferative state. In children, it is associated with familial immunodeficiency disease but most cases have no obvious etiology. In adults, nodular lymphoid hyperplasia is associated with immunocompromised status, including chemotherapy, acquired immunodeficiency viral infection, organ transplantation, and multiple polypoid lesions are noted in endoscopic findings and sometimes may be confused with family polypoid syndrome. We present a child with histological proof of focal intestinal nodular lymphoid hyperplasia that had a complete image study including negative results of ¹⁸F-fluoro-2-deoxyglucose positron emission tomography/computerized tomography analysis.     

Molecular-genetic analysis of ocular adnexal benign lymphoid hyperplasias by a two-step polymerase-chain-reaction

Summary Twelve biopsied ocular adnexal benign lymphoid hyperplasias (OABLH) satisfying benign histological criteria were investigated for clonal immunoglobulin (Ig) heavy-chain gene rearrangement by means of a two-step polymerase chain reaction (PCR) method using formalin-fixed and paraffin-embedded tissue. Of the 12, 4 (33%) demonstrated clear single bands of the rearranged gene for the Ig heavy-chain, of between 100 and 150 base pairs. The selected cases were all free of malignant lymphoma and all of the lesions were small (2×2–22×6 mm; median 4.5×3 mm). Histopathological and cytological features were not essentially different between monoclonal and non-monoclonal examples. Immunohistochemistry was of little benefit in separating the two. It is concluded that OABLH demonstrating a benign clinical course frequently contain monoclonal B cell populations suggesting a continuous progressive spectrum of lesions in B cell neoplasia. In addition, the significance of molecular-genetic analysis for OABLH and the utility of the two-step PCR method should be emphasized.Abbreviations OABLH ocular adnexal benign lymphoid hyperplasia - PCR polymerase chain reaction - bp base paris     

A Case of Intussusception and Lymphoid Hyperplasia in a Patient with AIDS

Idiopathic Intussusception in adults is rare. In tropical climates, enteric infection is causally implicated. Three cases of intussuseeption in AIDS patients have been reported, two of which were associated with enteric infection. We report the fourth case of ileocolonic Intussusception in an AIDS patient in whom lymphoid hyperplasia of the terminal ileum was found hut no infection documented. The relationship between lymphoid hyperplasia and Intussusception is discussed. The previous cases of AIDS and Intussusception are reviewed. Idiopathic Intussusception may become more prevalent as the number of AIDS cases increases, and must be considered in the differential diagnosis of abdominal pain in AIDS patients.     

Tumoral nasopharyngeal lymphoid hyperplasia in human immunodeficiency virus-infected patients

Two patients presented with a large tumoral nasopharyngeal lesion with obstructive symptoms, which suggested a malignant tumor. They were black men of Caribbean origin who were infected with human immunodeficiency virus 1. In both cases, histologic examination revealed intense but benign lymphoid follicular hyperplasia, and immunohistochemical studies were consistent with its polyclonal nature. DNA studies performed on tumoral tissue failed to disclose immunoglobulin or T-cell receptor gene rearrangements. In one biopsy specimen, DNA hybridization using Epstein-Barr virus-specific probes showed no evidence of Epstein-Barr virus-DNA sequences. The nasopharynx can be involved in the diffuse extranodal lymphoid hyperplasia associated with human immunodeficiency virus infection.     

Benign lymphoid hyperplasia of the duodenal bulb.

Four cases of benign lymphoid hyperplasia (BLH) of the duodenal bulb are reported. The roentgen findings of this entity are presented and the literature on BLH of the gastrointestinal tract is briefly reviewed.     

Familial adenomatous polyposis and duodenal lymphoma

The occurrence of duodenal polyposis is well recognized in familial adenomatous polyposis. Lymphoid hyperplasia in association with familial adenomatous polyposis usually occurs in the terminal ileum, but it can occur in the duodenum and may be endoscopically difficult to distinguish from an adenoma. A case report is presented in which a 54-yearold male with familial adenomatous polyposis, who 20 years earlier had a subtotal colectomy and ileorectal anastomosis, presented with a large rectal villous tumor and was found to have a duodenal extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. The role of lymphoid hyperplasia in the development of mucosa-associated lymphoid tissue lymphoma is discussed, as well as the issue of mucosa-associated lymphoid tissue lymphoma in familial adenomatous polyposis. In cases in which biopsies of polypoid lesions in patients with familial adenomatous polyposis show dense lymphoid aggregates, flow cytometry may assist in the diagnosis.     

Hypermethylation of the 5' region of the calcitonin gene is a property of human lymphoid and acute myeloid malignancies

An abnormal increase in numbers of CCGG sites methylated in the 5' region of the human calcitonin (CT) gene occurred in tumor cell DNA samples from 90% (17 of 19) of patients with non-Hodgkin's T and B cell lymphoid neoplasms and in 95% (21 of 22) of tumor cell DNA samples from patients with acute nonlymphocytic leukemia (ANLL). The changes were not seen in patients with chronic myelogenous leukemia (0 of 9). The abnormal methylation patterns appear to be a property only of transformed or malignant cells since they were not found in DNA from nonneoplastic adult tissues including sperm, early myeloid progenitor cells, benign lymphoid hyperplasia, peripheral lymphocytes stimulated to divide, or early myeloid progenitor cells (obtained by immunoaffinity using anti-My-10 antibody), but they did appear after Epstein-Barr virus transformation of lymphocytes. Moreover, during the course of therapy in patients with ANLL, the hypermethylation pattern reflects the presence of the leukemic clone even in normal-appearing granulocytes derived from this clone. The increased methylation of the CT gene may then provide an important molecular marker for biologic events in human cell transformation or tumor progression and may prove clinically useful in monitoring patients with lymphoid and acute myelogenous neoplasms.     

A case of adult-onset Still's disease complicated by non-Hodgkin's lymphoma

Left cervical lymphadenopathy developed in a 50-year-old male who had a history of adult-onset Still's disease for the preceding 18 months. Still's disease is characterized by rash, fever, and leukocytosis. Lymphadenopathy has been reported in about 60% of the patients, and most histopathologic studies have shown non-specific reactive hyperplasia. However, in this case, an open biopsy of the cervical node revealed a histology of diffuse large B-cell lymphoma. The B-cell malignant lymphoma that developed may have resulted from a sequential progression of a previous stage of benign lymphoproliferative lesion. Our case suggests that the pathophysiology of adult-onset Still's disease involves the stimulation of lymphoid systems to the point of progression towards lymphoma. Malignant lymphoma should be added to the list of life-threatening complications which, although rare, are associated with this disease.     

Diffuse lung cysts in lymphoid interstitial pneumonia: high-resolution CT and pathologic findings

Lymphoid interstitial pneumonia is part of a spectrum of pulmonary lymphoproliferative disorders that range from benign, small, and airway-centered cellular infiltrates (follicular bronchiolitis, nodular lymphoid hyperplasia) to low-grade malignant lymphoma. Most of the cases occur in patients with underlying autoimmune disease or immunodeficiency. The characteristic high-resolution computed tomography findings consist of diffuse ground-glass opacities, ill-defined centrilobular nodules, bronchovascular thickening, interlobular septal thickening, and scattered thin-walled cysts. The cysts may be seen in up to 80% of the patients and are typically few in number and measure less than 3 cm in diameter. This case illustrates extensive cysts as the predominant high-resolution computed tomography finding of idiopathic lymphoid interstitial pneumonia in a 64-year-old man who underwent unilateral lung transplant. Such extensive cystic disease and lung transplantation treatment has not been previously described.     

Glycolytic and Respiratory Enzyme Activity in Relation to Leucocyte Maturation

S ummary . Low activity of intramitochondrial dehydrogenases and of a mitochondrial membrane hydrogen shuttle system has been demonstrated cytochemically in the lymphoblast and in three Burkitt lymphoma cell lines; this contrasts with a relatively high activity of extramitochondrial glycolytic enzymes and may render these cells abnormally sensitive to glycolytic enzyme inhibition. This pattern of enzyme activity was not seen in normal and leukaemic myeloid cells at any stage of maturation, nor in lymphoid cells undergoing benign hyperplasia, and appears to be related to mitochondrial number. This explanation is in contrast to previous claims of specific enzyme deletions in solid tumours and in mouse lymphoma.     

Diagnostics and treatment of pulmonary BALT lymphoma: a report on four cases

Bronchus-associated lymphoid tissue (BALT) is a lymphoid aggregate located in the submucosal area of bronchioles and plays a central role in airway mucosal immunity by inducing the accumulation of secretory IgA-producing cells. Long-lasting antigen stimuli promote the hyperplasia of BALT, which may develop into pulmonary mucosa-associated lymphoma (baltoma). Most pulmonary lymphomas are low-grade B-cell lymphomas. We have recently treated four patients with BALT lymphoma and this is our first report on their diagnostics and treatment. Based on these cases we wanted to demonstrate the difficulties of differential diagnosis during bronchoscopic and computed tomography (CT) examinations as well as the pitfalls of thoracosurgical vs hemato-oncological treatments.     

Brunner＇s gland adenoma of duodenum： A case report and literature review

AIM: To analyze the clinicopathological features of Brunner‘s gland adenoma of the duodenum.METHODS: A rare case of Brunner‘s gland adenoma of the duodenum was described and related literature was reviewed.RESULTS: Brunner‘s gland adenoma of the duodenum appeared to be nodular hyperplasia of the normal Brunner‘s gland with an unusual admixture of normal tissues, including ducts, adipose tissue and lymphoid tissue. We suggested that it might be designated as a duodenal hamartoma rather than a true neoplasm.CONCLUSION: The most common location of the lesion is the posterior wall of the duodenum near the junction of its first and second portions. It can result in gastrointestinal hemorrhage and duodenal obstruction. Endoscopic polypectomy is a worthy treatment for benign Brunner‘s gland adenomas,as malignant changes in these tumors have never been proven.     

Malignant lymphoma of jejunum with common variable hypogammaglobulinemia and diffuse nodular hyperplasia of the small intestine. A case study and literature review.

We report a patient with common variable hypogammaglobulinemia and diffuse nodular lymphoid hyperplasia of the small intestine complicated by a jejunal malignant lymphoma. Immunopathological and histological studies showed a polymorphous centroblastic lymphoma with intracytoplasmatic IgM immunoglobulin and lambda light chains. Some mucosal nodules separate from the tumor mass showed atypical lymphoid cell populations similar to lymphoma cells, suggesting a transition between hyperplastic nodules and lymphoma nodules. Four similar cases, and six other patients with malignant lymphoma of the small intestine, associated with diffuse nodular lymphoid hyperplasia, but without immunodeficiency, have already been described. All these cases suggest that nodular lymphoid hyperplasia increases the risk of small intestine lymphoma.     

Benign Lymphoid Hyperplasia of the Stomach Mimicking Gastric Malignancy

A case of benign lymphoid hyperplasia of the stomach misdiagnosed as ulcerating gastric carcinoma is presented. The similarities in the clinical, roentgenologic and gastroscopic features as well as in the gross appearance of the two lesions are described and the features which help differentiation are highlighted. The pathologic picture suggested that the lesion possibly arose as a peptic ulcer and the clinical history further supports such a possibility.